@article {pmid38526062, year = {2024}, author = {Wielgoss, S and Van Dyken, JD and Velicer, GJ}, title = {Mutation rate and effective population size of the model cooperative bacterium Myxococcus xanthus.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evae066}, pmid = {38526062}, issn = {1759-6653}, abstract = {Intrinsic rates of genetic mutation have diverged greatly across taxa and exhibit statistical associations with several other parameters and features. These include effective population size (Ne), genome size, and gametic multicellularity, with the latter being associated with both increased mutation rates and decreased effective population sizes. However, data sufficient to test for possible relationships between microbial multicellularity and mutation rate (µ) are lacking. Here we report estimates of two key population-genetic parameters, Ne and µ, for Myxococcus xanthus, a bacterial model organism for the study of aggregative multicellular development, predation, and social swarming. To estimate µ, we conducted an ∼400-day mutation-accumulation (MA) experiment with 46 lineages subjected to regular single colony bottlenecks prior to clonal regrowth. Upon conclusion, we sequenced one clonal-isolate genome per lineage. Given collective evolution for 85,323 generations across all lines, we calculate a per base-pair mutation rate of ∼5.5 × 10-10 per site per generation, one of the highest mutation rates among free-living eubacteria. Given our estimate of µ, we derived Ne at ∼107 from neutral diversity at four-fold degenerate sites across two dozen M. xanthus natural isolates. This estimate is below average for eubacteria and strengthens an already clear negative correlation between µ and Ne in prokaryotes. The higher and lower than average mutation rate and Ne for M. xanthus, respectively, amplify the question of whether any features of its multicellular life-cycle - such as group-size reduction during fruiting-body development - or its highly structured spatial distribution have significantly influenced how these parameters have evolved.}, } @article {pmid38519635, year = {2024}, author = {}, title = {Multicellularity drives ecological diversity in a long-term evolution experiment.}, journal = {Nature ecology & evolution}, volume = {}, number = {}, pages = {}, pmid = {38519635}, issn = {2397-334X}, } @article {pmid38514634, year = {2024}, author = {Carreira de Paula, J and García Olmedo, P and Gómez-Moracho, T and Buendía-Abad, M and Higes, M and Martín-Hernández, R and Osuna, A and de Pablos, LM}, title = {Promastigote EPS secretion and haptomonad biofilm formation as evolutionary adaptations of trypanosomatid parasites for colonizing honeybee hosts.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {27}, pmid = {38514634}, issn = {2055-5008}, mesh = {Humans ; Bees ; Animals ; *Parasites ; Ecosystem ; *Trypanosomatina/parasitology ; Biological Evolution ; }, abstract = {Bees are major pollinators involved in the maintenance of all terrestrial ecosystems. Biotic and abiotic factors placing these insects at risk is a research priority for ecological and agricultural sustainability. Parasites are one of the key players of this global decline and the study of their mechanisms of action is essential to control honeybee colony losses. Trypanosomatid parasites and particularly the Lotmaria passim are widely spread in honeybees, however their lifestyle is poorly understood. In this work, we show how these parasites are able to differentiate into a new parasitic lifestyle: the trypanosomatid biofilms. Using different microscopic techniques, we demonstrated that the secretion of Extracellular Polymeric Substances by free-swimming unicellular promastigote forms is a prerequisite for the generation and adherence of multicellular biofilms to solid surfaces in vitro and in vivo. Moreover, compared to human-infective trypanosomatid parasites our study shows how trypanosomatid parasites of honeybees increases their resistance and thus resilience to drastic changes in environmental conditions such as ultralow temperatures and hypoosmotic shock, which would explain their success thriving within or outside their hosts. These results set up the basis for the understanding of the success of this group of parasites in nature and to unveil the impact of such pathogens in honeybees, a keystones species in most terrestrial ecosystems.}, } @article {pmid38517944, year = {2024}, author = {Phillips, JE and Pan, D}, title = {The Hippo kinase cascade regulates a contractile cell behavior and cell density in a close unicellular relative of animals.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {38517944}, issn = {2050-084X}, support = {EY015708/EY/NEI NIH HHS/United States ; }, abstract = {The genomes of close unicellular relatives of animals encode orthologs of many genes that regulate animal development. However, little is known about the function of such genes in unicellular organisms or the evolutionary process by which these genes came to function in multicellular development. The Hippo pathway, which regulates cell proliferation and tissue size in animals, is present in some of the closest unicellular relatives of animals, including the amoeboid organism Capsaspora owczarzaki. We previously showed that the Capsaspora ortholog of the Hippo pathway nuclear effector Yorkie/YAP/TAZ (coYki) regulates actin dynamics and the three-dimensional morphology of Capsaspora cell aggregates, but is dispensable for cell proliferation control (Phillips et al., 2022). However, the function of upstream Hippo pathway components, and whether and how they regulate coYki in Capsaspora, remained unknown. Here, we analyze the function of the upstream Hippo pathway kinases coHpo and coWts in Capsaspora by generating mutant lines for each gene. Loss of either kinase results in increased nuclear localization of coYki, indicating an ancient, premetazoan origin of this Hippo pathway regulatory mechanism. Strikingly, we find that loss of either kinase causes a contractile cell behavior and increased density of cell packing within Capsaspora aggregates. We further show that this increased cell density is not due to differences in proliferation, but rather actomyosin-dependent changes in the multicellular architecture of aggregates. Given its well-established role in cell density-regulated proliferation in animals, the increased density of cell packing in coHpo and coWts mutants suggests a shared and possibly ancient and conserved function of the Hippo pathway in cell density control. Together, these results implicate cytoskeletal regulation but not proliferation as an ancestral function of the Hippo pathway kinase cascade and uncover a novel role for Hippo signaling in regulating cell density in a proliferation-independent manner.}, } @article {pmid38516913, year = {2024}, author = {Dsilva, GJ and Galande, S}, title = {From sequence to consequence: Deciphering the complex cisregulatory landscape.}, journal = {Journal of biosciences}, volume = {49}, number = {}, pages = {}, pmid = {38516913}, issn = {0973-7138}, abstract = {Cell type-specific expression of genes plays a pivotal role in the development and evolution of multicellular organisms over millions of years. The majority of regulatory control resides within the non-coding regions of the genome, referred to as 'dark matter', which contains cis-regulatory modules. These cis-regulatory modules function collectively and can impact gene expression even when located far from the target gene, exhibiting context-specific behaviour. Consequently, the cis-regulatory code governing gene expression patterns is intricate, in contrast to the universally understood genetic code. This overview centres on the current knowledge regarding cis-regulatory elements, primarily enhancers and their role in governing the spatiotemporal gene expression patterns, and how they have evolved and adapted across different species.}, } @article {pmid38513029, year = {2024}, author = {Luthringer, R and Raphalen, M and Guerra, C and Colin, S and Martinho, C and Zheng, M and Hoshino, M and Badis, Y and Lipinska, AP and Haas, FB and Barrera-Redondo, J and Alva, V and Coelho, SM}, title = {Repeated co-option of HMG-box genes for sex determination in brown algae and animals.}, journal = {Science (New York, N.Y.)}, volume = {383}, number = {6689}, pages = {eadk5466}, doi = {10.1126/science.adk5466}, pmid = {38513029}, issn = {1095-9203}, abstract = {In many eukaryotes, genetic sex determination is not governed by XX/XY or ZW/ZZ systems but by a specialized region on the poorly studied U (female) or V (male) sex chromosomes. Previous studies have hinted at the existence of a dominant male-sex factor on the V chromosome in brown algae, a group of multicellular eukaryotes distantly related to animals and plants. The nature of this factor has remained elusive. Here, we demonstrate that an HMG-box gene acts as the male-determining factor in brown algae, mirroring the role HMG-box genes play in sex determination in animals. Over a billion-year evolutionary timeline, these lineages have independently co-opted the HMG box for male determination, representing a paradigm for evolution's ability to recurrently use the same genetic "toolkit" to accomplish similar tasks.}, } @article {pmid38500675, year = {2024}, author = {Narula, K and Sinha, A and Choudhary, P and Ghosh, S and Elagamey, E and Sharma, A and Sengupta, A and Chakraborty, N and Chakraborty, S}, title = {Combining extracellular matrix proteome and phosphoproteome of chickpea and meta-analysis reveal novel proteoforms and evolutionary significance of clade-specific wall-associated events in plant.}, journal = {Plant direct}, volume = {8}, number = {3}, pages = {e572}, pmid = {38500675}, issn = {2475-4455}, abstract = {Extracellular matrix (ECM) plays central roles in cell architecture, innate defense and cell wall integrity (CWI) signaling. During transition to multicellularity, modular domain structures of ECM proteins and proteoforms have evolved due to continuous adaptation across taxonomic clades under different ecological niche. Although this incredible diversity has to some extent been investigated at protein level, extracellular phosphorylation events and molecular evolution of ECM proteoform families remains unexplored. We developed matrisome proteoform atlas in a grain legume, chickpea and performed meta-analyses of 74 plant matrisomes. MS/MS analysis identified 1,424 proteins and 315 phosphoproteins involved in diverse functions. Cross-species ECM protein network identified proteoforms associated with CWI maintenance system. Phylogenetic characterization of eighteen matrix protein families highlighted the role of taxon-specific paralogs and orthologs. Novel information was acquired on gene expansion and loss, co-divergence, sub functionalization and neofunctionalization during evolution. Modular networks of matrix protein families and hub proteins showed higher diversity across taxonomic clades than among organs. Furthermore, protein families differ in nonsynonymous to synonymous substitution rates. Our study pointed towards the matrix proteoform functionality, sequence divergence variation, interactions between wall remodelers and molecular evolution using a phylogenetic framework. This is the first report on comprehensive matrisome proteoform network illustrating presence of CWI signaling proteins in land plants.}, } @article {pmid38334416, year = {2024}, author = {Földi, C and Merényi, Z and Balázs, B and Csernetics, Á and Miklovics, N and Wu, H and Hegedüs, B and Virágh, M and Hou, Z and Liu, X-B and Galgóczy, L and Nagy, LG}, title = {Snowball: a novel gene family required for developmental patterning of fruiting bodies of mushroom-forming fungi (Agaricomycetes).}, journal = {mSystems}, volume = {9}, number = {3}, pages = {e0120823}, pmid = {38334416}, issn = {2379-5077}, support = {LP2019-13/2019//Hungarian Academy of Sciences/ ; KDP-17-4/PALY-2021//Ministry of Innovation and Technology (Hungary)/ ; OTKA 142188//National Research Development and Innovation Office (Hungary)/ ; }, mesh = {Fruiting Bodies, Fungal/genetics ; Phylogeny ; Fungal Proteins/genetics ; *Agaricales/genetics ; *Basidiomycota/metabolism ; *Ascomycota/metabolism ; }, abstract = {UNLABELLED: The morphogenesis of sexual fruiting bodies of fungi is a complex process determined by a genetically encoded program. Fruiting bodies reached the highest complexity levels in the Agaricomycetes; yet, the underlying genetics is currently poorly known. In this work, we functionally characterized a highly conserved gene termed snb1, whose expression level increases rapidly during fruiting body initiation. According to phylogenetic analyses, orthologs of snb1 are present in almost all agaricomycetes and may represent a novel conserved gene family that plays a substantial role in fruiting body development. We disrupted snb1 using CRISPR/Cas9 in the agaricomycete model organism Coprinopsis cinerea. snb1 deletion mutants formed unique, snowball-shaped, rudimentary fruiting bodies that could not differentiate caps, stipes, and lamellae. We took advantage of this phenotype to study fruiting body differentiation using RNA-Seq analyses. This revealed differentially regulated genes and gene families that, based on wild-type RNA-Seq data, were upregulated early during development and showed tissue-specific expression, suggesting a potential role in differentiation. Taken together, the novel gene family of snb1 and the differentially expressed genes in the snb1 mutants provide valuable insights into the complex mechanisms underlying developmental patterning in the Agaricomycetes.

IMPORTANCE: Fruiting bodies of mushroom-forming fungi (Agaricomycetes) are complex multicellular structures, with a spatially and temporally integrated developmental program that is, however, currently poorly known. In this study, we present a novel, conserved gene family, Snowball (snb), termed after the unique, differentiation-less fruiting body morphology of snb1 knockout strains in the model mushroom Coprinopsis cinerea. snb is a gene of unknown function that is highly conserved among agaricomycetes and encodes a protein of unknown function. A comparative transcriptomic analysis of the early developmental stages of differentiated wild-type and non-differentiated mutant fruiting bodies revealed conserved differentially expressed genes which may be related to tissue differentiation and developmental patterning fruiting body development.}, } @article {pmid38499447, year = {2024}, author = {Piccini, C and Martínez de la Escalera, G and Segura, A and Croci, C and Kruk, C}, title = {The Microcystis-microbiome interactions: origins of the colonial lifestyle.}, journal = {FEMS microbiology ecology}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsec/fiae035}, pmid = {38499447}, issn = {1574-6941}, abstract = {Species of the Microcystis genus are the most common bloom-forming toxic cyanobacteria worldwide. They belong to a clade of unicellular cyanobacteria whose ability to reach high biomasses during blooms is linked to the formation of colonies. Colonial lifestyle provides several advantages under stressing conditions of light intensity, ultraviolet light, toxic substances and grazing. The progression from a single-celled organism to multicellularity in Microcystis has usually been interpreted as individual phenotypic responses of the cyanobacterial cells to the environment. Here, we synthesize current knowledge about Microcystis colonial lifestyle and its role in the organism ecology. We then briefly review the available information on Microcystis microbiome and propose that changes leading from single cells to colonies are the consequence of specific and tightly regulated signals between the cyanobacterium and its microbiome through a biofilm-like mechanism. The resulting colony is a multi-specific community of interdependent microorganisms.}, } @article {pmid38498818, year = {2024}, author = {Bozdag, GO and Szeinbaum, N and Conlin, PL and Chen, K and Fos, SM and Garcia, A and Penev, PI and Schaible, GA and Trubl, G}, title = {Chapter 5: Major Biological Innovations in the History of Life on Earth.}, journal = {Astrobiology}, volume = {24}, number = {S1}, pages = {S107-S123}, doi = {10.1089/ast.2021.0119}, pmid = {38498818}, issn = {1557-8070}, abstract = {All organisms living on Earth descended from a single, common ancestral population of cells, known as LUCA-the last universal common ancestor. Since its emergence, the diversity and complexity of life have increased dramatically. This chapter focuses on four key biological innovations throughout Earth's history that had a significant impact on the expansion of phylogenetic diversity, organismal complexity, and ecospace habitation. First is the emergence of the last universal common ancestor, LUCA, which laid the foundation for all life-forms on Earth. Second is the evolution of oxygenic photosynthesis, which resulted in global geochemical and biological transformations. Third is the appearance of a new type of cell-the eukaryotic cell-which led to the origin of a new domain of life and the basis for complex multicellularity. Fourth is the multiple independent origins of multicellularity, resulting in the emergence of a new level of complex individuality. A discussion of these four key events will improve our understanding of the intertwined history of our planet and its inhabitants and better inform the extent to which we can expect life at different degrees of diversity and complexity elsewhere.}, } @article {pmid38497809, year = {2024}, author = {Hörandl, E}, title = {Apomixis and the paradox of sex in plants.}, journal = {Annals of botany}, volume = {}, number = {}, pages = {}, doi = {10.1093/aob/mcae044}, pmid = {38497809}, issn = {1095-8290}, abstract = {BACKGROUND: The predominance of sex in eukaryotes, despite the high costs of meiosis and mating, is still an evolutionary enigma. Many theories have been proposed, none of them being conclusive on its own, and they are partly not well applicable to land plants. Sexual reproduction is obligate in embryophytes for the great majority of species.

SCOPE: This review will compare the main forms of sexual and asexual reproduction in ferns and angiosperms, based on the generation cycling of sporophyte and gametophyte (leaving vegetative propagation aside). The benefits of sexual reproduction for maintenance of genomic integrity compared to asexuality will be discussed in the light of developmental, evolutionary, genetic and phylogenetic studies.

CONCLUSIONS: Asexual reproduction represents modifications of the sexual pathway, with various forms of facultative sexuality. For sexual land plants, meiosis provides direct DNA repair mechanisms of oxidative damage in reproductive tissues. The ploidy alternations of meiosis-syngamy cycles, and prolonged, multicellular stages in the haploid phase in the gametophytes provide a high efficiency of purifying selection against recessive deleterious mutations. Asexual lineages might buffer effects of such mutations via polyploidy, and can purge the mutational load via facultative sexuality. The role of organelle-nuclear genome compatibility for maintenance of genome integrity is still not well understood. The costs of mating are in plants in general low because of predominant hermaphroditism. Phylogenetic patterns in the Archaeplastid clade suggest that high frequencies of sexuality in land plants are concomitant with a stepwise increase of intrinsic and extrinsic stress factors. Furthermore, expansion of genome size in land plants would increase the potential mutational load. Sexual reproduction appears to be essential for keeping long term genomic integrity, and only rare combinations of extrinsic and intrinsic factors allow for shifts to asexuality.}, } @article {pmid38493178, year = {2024}, author = {Bing, J and Guan, Z and Zheng, T and Ennis, CL and Nobile, CJ and Chen, C and Chu, H and Huang, G}, title = {Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2381}, pmid = {38493178}, issn = {2041-1723}, support = {31930005 and 82272359//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32170193 and 32000018//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32170193 and 32000018//National Natural Science Foundation of China (National Science Foundation of China)/ ; R35GM124594//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Animals ; Mice ; Candida/genetics ; *Candidiasis/microbiology ; Candida auris ; Saccharomyces cerevisiae ; Phenotype ; *Sepsis ; Antifungal Agents ; Microbial Sensitivity Tests ; Mammals ; }, abstract = {Candida auris has become a serious threat to public health. The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive C. auris multicellular aggregative morphology in the murine host during systemic infection. C. auris aggregative cells accumulate in the brain and exhibit obvious advantages over the single-celled yeast-form cells during systemic infection. Genetic mutations, specifically de novo point mutations in genes associated with cell division or budding processes, underlie the rapid evolution of this aggregative phenotype. Most mutated C. auris genes are associated with the regulation of cell wall integrity, cytokinesis, cytoskeletal properties, and cellular polarization. Moreover, the multicellular aggregates are notably more recalcitrant to the host antimicrobial peptides LL-37 and PACAP relative to the single-celled yeast-form cells. Overall, to survive in the host, C. auris can rapidly evolve a multicellular aggregative morphology via genetic mutations.}, } @article {pmid38492155, year = {2024}, author = {Li, X and Gao, T and Ma, X and Zhong, J and Qin, L and Nian, Y and Wang, X and Luo, Y}, title = {Extraction and identification of exosomes from three different sources of human ovarian granulosa cells and analysis of their differential miRNA expression profiles.}, journal = {Journal of assisted reproduction and genetics}, volume = {}, number = {}, pages = {}, pmid = {38492155}, issn = {1573-7330}, support = {81660806//National Natural Science Foundation of China/ ; 82260947//National Natural Science Foundation of China/ ; }, abstract = {OBJECTIVE: As important functional cells in the ovary, ovarian granulosa cells are involved in the regulation of oocyte growth and development and play an important role in the study of female fertility preservation. Based on the importance of granulosa cell functionalism, in this study, we analyzed the exosome secretion capacity of human ovarian granulosa cells (SVOG/KGN-cell line, PGC-primary cells) and the differences in their miRNA expression.

METHODS: Cells were identified by hematoxylin-eosin staining (HE) and FSHR immunofluorescence staining; CCK8 and colony-forming assay were performed to compare cell proliferation capacity; exosomes were extracted and identified by ultra-high speed centrifugation, transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot analysis (WB), and the expression profile of each cellular exosomal miRNA was analyzed by miRNA high-throughput sequencing.

RESULTS: The proliferative abilities of the three granulosa cells differed, but all had the ability to secrete exosomes. In the exosomes of SVOG, KGN, and PGC cells, 218, 327, and 471 miRNAs were detected, respectively. When compared to the exosomal miRNAs of PGC cells, 111 miRNAs were significantly different in SVOG, and 70 miRNAs were washed two significantly different in KGN cells. These differential miRNA functions were mainly enriched in the cell cycle, cell division/differentiation, multicellular biogenesis, and protein binding.

CONCLUSION: Human ovarian granulosa cells of different origins are capable of secreting exosomes, but there are still some differences in their exosomes and exosomal miRNAs, and experimental subjects should be selected rationally according to the actual situation.}, } @article {pmid38486107, year = {2024}, author = {Pineau, RM and Libby, E and Demory, D and Lac, DT and Day, TC and Bravo, P and Yunker, PJ and Weitz, JS and Bozdag, GO and Ratcliff, WC}, title = {Emergence and maintenance of stable coexistence during a long-term multicellular evolution experiment.}, journal = {Nature ecology & evolution}, volume = {}, number = {}, pages = {}, pmid = {38486107}, issn = {2397-334X}, support = {DEB-1845363//NSF | BIO | Division of Environmental Biology (DEB)/ ; 1845363//NSF | BIO | Division of Environmental Biology (DEB)/ ; 5R35GM138030//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 5R35GM138030//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 1R35GM138354//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 1R35GM138354//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 1R35GM138354//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R35GM138030//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, abstract = {The evolution of multicellular life spurred evolutionary radiations, fundamentally changing many of Earth's ecosystems. Yet little is known about how early steps in the evolution of multicellularity affect eco-evolutionary dynamics. Through long-term experimental evolution, we observed niche partitioning and the adaptive divergence of two specialized lineages from a single multicellular ancestor. Over 715 daily transfers, snowflake yeast were subjected to selection for rapid growth, followed by selection favouring larger group size. Small and large cluster-forming lineages evolved from a monomorphic ancestor, coexisting for over ~4,300 generations, specializing on divergent aspects of a trade-off between growth rate and survival. Through modelling and experimentation, we demonstrate that coexistence is maintained by a trade-off between organismal size and competitiveness for dissolved oxygen. Taken together, this work shows how the evolution of a new level of biological individuality can rapidly drive adaptive diversification and the expansion of a nascent multicellular niche, one of the most historically impactful emergent properties of this evolutionary transition.}, } @article {pmid38481381, year = {2024}, author = {Wu, Z and Liu, D and Ou, Y and Xu, Z and Heng, G and Liu, W and Fu, N and Wang, J and Jiang, D and Gan, L and Dong, J and Wang, X and Chen, Z and Zhang, L and Zhang, C}, title = {Mechanism and endoscopic-treatment-induced evolution of biliary non-anastomotic stricture after liver transplantation revealed by single-cell RNA sequencing.}, journal = {Clinical and translational medicine}, volume = {14}, number = {3}, pages = {e1622}, pmid = {38481381}, issn = {2001-1326}, support = {2022TIAD-GPX0236//Technical Innovation and Application of Chongqing/ ; 2022TIAD-GPX0238//Technical Innovation and Application of Chongqing/ ; 82270687//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Liver Transplantation/adverse effects ; Constriction, Pathologic/surgery/etiology ; Retrospective Studies ; Endothelial Cells ; Sequence Analysis, RNA ; Bile Acids and Salts ; }, abstract = {BACKGROUND: Biliary complications, especially non-anastomotic stricture (NAS), are the main complications after liver transplantation. Insufficient sampling and no recognized animal models obstruct the investigation. Thus, the mechanisms and alterations that occur during endoscopic treatment (ET) of NAS remain unclear.

METHODS: Samples were obtained with endoscopic forceps from the hilar bile ducts of NAS patients receiving continuous biliary stent implantation after diagnosis. Retrospective analysis of multiple studies indicated that the duration of ET for NAS was approximately 1-2 years. Thus, we divided the patients into short-term treatment (STT) and long-term treatment (LTT) groups based on durations of less or more than 1 year. Samples were subjected to single-cell RNA sequencing. Transcriptomic differences between STT and normal groups were defined as the NAS mechanism. Similarly, alterations from STT to LTT groups were regarded as endoscopic-treatment-induced evolution.

RESULTS: In NAS, inflammation and immune-related pathways were upregulated in different cell types, with nonimmune cells showing hypoxia pathway upregulation and immune cells showing ATP metabolism pathway upregulation, indicating heterogeneity. We confirmed a reduction in bile acid metabolism-related SPP1[+] epithelial cells in NAS. Increases in proinflammatory and profibrotic fibroblast subclusters indicated fibrotic progression in NAS. Furthermore, immune disorders in NAS were exacerbated by an increase in plasma cells and dysfunction of NK and NKT cells. ET downregulated multicellular immune and inflammatory responses and restored epithelial and endothelial cell proportions.

CONCLUSIONS: This study reveals the pathophysiological and genetic mechanisms and evolution of NAS induced by ET, thereby providing preventive and therapeutic insights into NAS.

HIGHLIGHTS: For the first time, single-cell transcriptome sequencing was performed on the bile ducts of patients with biliary complications. scRNA-seq analysis revealed distinct changes in the proportion and phenotype of multiple cell types during Nonanastomotic stricture (NAS) and endoscopic treatment. A reduction in bile acid metabolism-related SPP1+ epithelial cells and VEGFA+ endothelial cells, along with explosive infiltration of plasma cells and dysfunction of T and NK cells in NAS patients. SPP1+ macrophages and BST2+ T cells might serve as a surrogate marker for predicting endoscopic treatment.}, } @article {pmid38476944, year = {2024}, author = {von Hoyningen-Huene, AJE and Bang, C and Rausch, P and Rühlemann, M and Fokt, H and He, J and Jensen, N and Knop, M and Petersen, C and Schmittmann, L and Zimmer, T and Baines, JF and Bosch, TCG and Hentschel, U and Reusch, TBH and Roeder, T and Franke, A and Schulenburg, H and Stukenbrock, E and Schmitz, RA}, title = {The archaeome in metaorganism research, with a focus on marine models and their bacteria-archaea interactions.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1347422}, pmid = {38476944}, issn = {1664-302X}, abstract = {Metaorganism research contributes substantially to our understanding of the interaction between microbes and their hosts, as well as their co-evolution. Most research is currently focused on the bacterial community, while archaea often remain at the sidelines of metaorganism-related research. Here, we describe the archaeome of a total of eleven classical and emerging multicellular model organisms across the phylogenetic tree of life. To determine the microbial community composition of each host, we utilized a combination of archaea and bacteria-specific 16S rRNA gene amplicons. Members of the two prokaryotic domains were described regarding their community composition, diversity, and richness in each multicellular host. Moreover, association with specific hosts and possible interaction partners between the bacterial and archaeal communities were determined for the marine models. Our data show that the archaeome in marine hosts predominantly consists of Nitrosopumilaceae and Nanoarchaeota, which represent keystone taxa among the porifera. The presence of an archaeome in the terrestrial hosts varies substantially. With respect to abundant archaeal taxa, they harbor a higher proportion of methanoarchaea over the aquatic environment. We find that the archaeal community is much less diverse than its bacterial counterpart. Archaeal amplicon sequence variants are usually host-specific, suggesting adaptation through co-evolution with the host. While bacterial richness was higher in the aquatic than the terrestrial hosts, a significant difference in diversity and richness between these groups could not be observed in the archaeal dataset. Our data show a large proportion of unclassifiable archaeal taxa, highlighting the need for improved cultivation efforts and expanded databases.}, } @article {pmid38471558, year = {2024}, author = {Jung, J and Loschko, T and Reich, S and Rassoul-Agha, M and Werner, MS}, title = {Newly identified nematodes from the Great Salt Lake are associated with microbialites and specially adapted to hypersaline conditions.}, journal = {Proceedings. Biological sciences}, volume = {291}, number = {2018}, pages = {20232653}, pmid = {38471558}, issn = {1471-2954}, mesh = {Animals ; *Ecosystem ; Lakes/chemistry ; Phylogeny ; *Nematoda ; Bacteria ; }, abstract = {Extreme environments enable the study of simplified food-webs and serve as models for evolutionary bottlenecks and early Earth ecology. We investigated the biodiversity of invertebrate meiofauna in the benthic zone of the Great Salt Lake (GSL), Utah, USA, one of the most hypersaline lake systems in the world. The hypersaline bays within the GSL are currently thought to support only two multicellular animals: brine fly larvae and brine shrimp. Here, we report the presence, habitat, and microbial interactions of novel free-living nematodes. Nematode diversity drops dramatically along a salinity gradient from a freshwater river into the south arm of the lake. In Gilbert Bay, nematodes primarily inhabit reef-like organosedimentary structures built by bacteria called microbialites. These structures likely provide a protective barrier to UV and aridity, and bacterial associations within them may support life in hypersaline environments. Notably, sampling from Owens Lake, another terminal lake in the Great Basin that lacks microbialites, did not recover nematodes from similar salinities. Phylogenetic divergence suggests that GSL nematodes represent previously undescribed members of the family Monhysteridae-one of the dominant fauna of the abyssal zone and deep-sea hydrothermal vents. These findings update our understanding of halophile ecosystems and the habitable limit of animals.}, } @article {pmid38474088, year = {2024}, author = {Jiménez-López, D and Xoconostle-Cázares, B and Calderón-Pérez, B and Vargas-Hernández, BY and Núñez-Muñoz, LA and Ramírez-Pool, JA and Ruiz-Medrano, R}, title = {Evolutionary and Structural Analysis of PP16 in Viridiplantae.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, doi = {10.3390/ijms25052839}, pmid = {38474088}, issn = {1422-0067}, support = {781282//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; }, abstract = {Members of the phloem protein 16 (PP16) gene family are induced by elicitors in rice and the corresponding proteins from cucurbits, which display RNA binding and intercellular transport activities, are accumulated in phloem sap. These proteins facilitate the movement of protein complexes through the phloem translocation flow and may be involved in the response to water deficit, among other functions. However, there is scant information regarding their function in other plants, including the identification of paralog genes in non-vascular plants and chlorophytes. In the present work, an evolutionary and structural analysis of the PP16 family in green plants (Viridiplantae) was carried out. Data mining in different databases indicated that PP16 likely originated from a larger gene present in an ancestral lineage that gave rise to chlorophytes and multicellular plants. This gene encodes a protein related to synaptotagmin, which is involved in vesicular transport in animal systems, although other members of this family play a role in lipid turnover in endomembranes and organelles. These proteins contain a membrane-binding C2 domain shared with PP16 proteins in vascular plants. In silico analysis of the predicted structure of the PP16 protein family identified several β-sheets, one α-helix, and intrinsically disordered regions. PP16 may have been originally involved in vesicular trafficking and/or membrane maintenance but specialized in long-distance signaling during the emergence of the plant vascular system.}, } @article {pmid38472019, year = {2024}, author = {Cui, L and Zhu, K and Li, R and Chang, C and Wu, L and Liu, W and Fu, D and Liu, P and Qiu, H and Tang, G and Li, Q and Gaines, RR and Tao, Y and Wang, Y and Li, J and Zhang, X}, title = {The Cambrian microfossil Qingjiangonema reveals the co-evolution of sulfate-reducing bacteria and the oxygenation of Earth's surface.}, journal = {Science bulletin}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.scib.2024.03.001}, pmid = {38472019}, issn = {2095-9281}, abstract = {Sulfate reduction is an essential metabolism that maintains biogeochemical cycles in marine and terrestrial ecosystems. Sulfate reducers are exclusively prokaryotic, phylogenetically diverse, and may have evolved early in Earth's history. However, their origin is elusive and unequivocal fossils are lacking. Here we report a new microfossil, Qingjiangonema cambria, from ∼518-million-year-old black shales that yield the Qingjiang biota. Qingjiangonema is a long filamentous form comprising hundreds of cells filled by equimorphic and equidimensional pyrite microcrystals with a light sulfur isotope composition. Multiple lines of evidence indicate Qingjiangonema was a sulfate-reducing bacterium that exhibits similar patterns of cell organization to filamentous forms within the phylum Desulfobacterota, including the sulfate-reducing Desulfonema and sulfide-oxidizing cable bacteria. Phylogenomic analyses confirm separate, independent origins of multicellularity in Desulfonema and in cable bacteria. Molecular clock analyses infer that the Desulfobacterota, which encompass a majority of sulfate-reducing taxa, diverged ∼2.41 billion years ago during the Paleoproterozoic Great Oxygenation Event, while cable bacteria diverged ∼0.56 billion years ago during or immediately after the Neoproterozoic Oxygenation Event. Taken together, we interpret Qingjiangonema as a multicellular sulfate-reducing microfossil and propose that cable bacteria evolved from a multicellular filamentous sulfate-reducing ancestor. We infer that the diversification of the Desulfobacterota and the origin of cable bacteria may have been responses to oxygenation events in Earth's history.}, } @article {pmid38465473, year = {2024}, author = {Borland, G and Wilkie, SE and Thomson, J and Wang, Z and Tullet, JMA and Alic, N and Selman, C}, title = {Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan.}, journal = {Aging cell}, volume = {}, number = {}, pages = {e14141}, doi = {10.1111/acel.14141}, pmid = {38465473}, issn = {1474-9726}, support = {BB/S014357/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/N013166/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {The genetic pathways that modulate ageing in multicellular organisms are typically highly conserved across wide evolutionary distances. Recently RNA polymerase III (Pol III) was shown to promote ageing in yeast, C. elegans and D. melanogaster. In this study we investigated the role of Pol III in mammalian ageing using C57BL/6N mice heterozygous for Pol III (Polr3b[+/-]). We identified sexually dimorphic, organ-specific beneficial as well as detrimental effects of the Polr3b[+/-] mutation on health. Female Polr3b[+/-] mice displayed improved bone health during ageing, but their ability to maintain an effective gut barrier function was compromised and they were susceptible to idiopathic dermatitis (ID). In contrast, male Polr3b[+/-] mice were lighter than wild-type (WT) males and had a significantly improved gut barrier function in old age. Several metabolic parameters were affected by both age and sex, but no genotype differences were detected. Neither male nor female Polr3b[+/-] mice were long-lived compared to WT controls. Overall, we find no evidence that a reduced Pol III activity extends mouse lifespan but we do find some potential organ- and sex-specific benefits for old-age health.}, } @article {pmid38462458, year = {2023}, author = {Libertini, G}, title = {Phenoptosis and the Various Types of Natural Selection.}, journal = {Biochemistry. Biokhimiia}, volume = {88}, number = {12}, pages = {2007-2022}, doi = {10.1134/S0006297923120052}, pmid = {38462458}, issn = {1608-3040}, abstract = {In the first description of evolution, the fundamental mechanism is the natural selection favoring the individuals best suited for survival and reproduction (selection at the individual level or classical Darwinian selection). However, this is a very reductive description of natural selection that does not consider or explain a long series of known phenomena, including those in which an individual sacrifices or jeopardizes his life on the basis of genetically determined mechanisms (i.e., phenoptosis). In fact, in addition to (i) selection at the individual level, it is essential to consider other types of natural selection such as those concerning: (ii) kin selection and some related forms of group selection; (iii) the interactions between the innumerable species that constitute a holobiont; (iv) the origin of the eukaryotic cell from prokaryotic organisms; (v) the origin of multicellular eukaryotic organisms from unicellular organisms; (vi) eusociality (e.g., in many species of ants, bees, termites); (vii) selection at the level of single genes, or groups of genes; (viii) the interactions between individuals (or more precisely their holobionts) of the innumerable species that make up an ecosystem. These forms of natural selection, which are all effects and not violations of the classical Darwinian selection, also show how concepts as life, species, individual, and phenoptosis are somewhat not entirely defined and somehow arbitrary. Furthermore, the idea of organisms selected on the basis of their survival and reproduction capabilities is intertwined with that of organisms also selected on the basis of their ability to cooperate and interact, even by losing their lives or their distinct identities.}, } @article {pmid38459017, year = {2024}, author = {Stanojković, A and Skoupý, S and Johannesson, H and Dvořák, P}, title = {The global speciation continuum of the cyanobacterium Microcoleus.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2122}, pmid = {38459017}, issn = {2041-1723}, support = {19-12994Y//Grantová Agentura České Republiky (Grant Agency of the Czech Republic)/ ; 23-06507S//Grantová Agentura České Republiky (Grant Agency of the Czech Republic)/ ; }, mesh = {*Genetic Speciation ; *Genetic Drift ; Gene Flow ; Genome ; Phylogeny ; }, abstract = {Speciation is a continuous process driven by genetic, geographic, and ecological barriers to gene flow. It is widely investigated in multicellular eukaryotes, yet we are only beginning to comprehend the relative importance of mechanisms driving the emergence of barriers to gene flow in microbial populations. Here, we explored the diversification of the nearly ubiquitous soil cyanobacterium Microcoleus. Our dataset consisted of 291 genomes, of which 202 strains and eight herbarium specimens were sequenced for this study. We found that Microcoleus represents a global speciation continuum of at least 12 lineages, which radiated during Eocene/Oligocene aridification and exhibit varying degrees of divergence and gene flow. The lineage divergence has been driven by selection, geographical distance, and the environment. Evidence of genetic divergence and selection was widespread across the genome, but we identified regions of exceptional differentiation containing candidate genes associated with stress response and biosynthesis of secondary metabolites.}, } @article {pmid38457507, year = {2024}, author = {Montrose, K and Lac, DT and Burnetti, AJ and Tong, K and Bozdag, GO and Hukkanen, M and Ratcliff, WC and Saarikangas, J}, title = {Proteostatic tuning underpins the evolution of novel multicellular traits.}, journal = {Science advances}, volume = {10}, number = {10}, pages = {eadn2706}, pmid = {38457507}, issn = {2375-2548}, abstract = {The evolution of multicellularity paved the way for the origin of complex life on Earth, but little is known about the mechanistic basis of early multicellular evolution. Here, we examine the molecular basis of multicellular adaptation in the multicellularity long-term evolution experiment (MuLTEE). We demonstrate that cellular elongation, a key adaptation underpinning increased biophysical toughness and organismal size, is convergently driven by down-regulation of the chaperone Hsp90. Mechanistically, Hsp90-mediated morphogenesis operates by destabilizing the cyclin-dependent kinase Cdc28, resulting in delayed mitosis and prolonged polarized growth. Reinstatement of Hsp90 or Cdc28 expression resulted in shortened cells that formed smaller groups with reduced multicellular fitness. Together, our results show how ancient protein folding systems can be tuned to drive rapid evolution at a new level of biological individuality by revealing novel developmental phenotypes.}, } @article {pmid38447933, year = {2024}, author = {Park, S and Cho, SW}, title = {Bioengineering toolkits for potentiating organoid therapeutics.}, journal = {Advanced drug delivery reviews}, volume = {}, number = {}, pages = {115238}, doi = {10.1016/j.addr.2024.115238}, pmid = {38447933}, issn = {1872-8294}, abstract = {Organoids are three-dimensional, multicellular constructs that recapitulate the structural and functional features of specific organs. Because of these characteristics, organoids have been widely applied in biomedical research in recent decades. Remarkable advancements in organoid technology have positioned them as promising candidates for regenerative medicine. However, current organoids still have limitations, such as the absence of internal vasculature, limited functionality, and a small size that is not commensurate with that of actual organs. These limitations hinder their survival and regenerative effects after transplantation. Another significant concern is the reliance on mouse tumor-derived matrix in organoid culture, which is unsuitable for clinical translation due to its tumor origin and safety issues. Therefore, our aim is to describe engineering strategies and alternative biocompatible materials that can facilitate the practical applications of organoids in regenerative medicine. Furthermore, we highlight meaningful progress in organoid transplantation, with a particular emphasis on the functional restoration of various organs.}, } @article {pmid38440346, year = {2024}, author = {Prondzynski, M and Pioner, JM and Sala, L and Bellin, M and Meraviglia, V}, title = {Editorial: Advances in pluripotent stem cell-based in vitro models of the human heart for cardiac physiology, disease modeling and clinical applications.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1378495}, doi = {10.3389/fphys.2024.1378495}, pmid = {38440346}, issn = {1664-042X}, } @article {pmid38437572, year = {2024}, author = {Szathmáry, E}, title = {Nonadaptive onset of complex multicellularity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {11}, pages = {e2401220121}, doi = {10.1073/pnas.2401220121}, pmid = {38437572}, issn = {1091-6490}, } @article {pmid38436556, year = {2024}, author = {Matsumoto, H and Ueda, M}, title = {Polarity establishment in the plant zygote at a glance.}, journal = {Journal of cell science}, volume = {137}, number = {5}, pages = {}, doi = {10.1242/jcs.261809}, pmid = {38436556}, issn = {1477-9137}, support = {//Japan Advanced Plant Science Network/ ; JP21K20650//Japan Society for the Promotion of Science/ ; JPMJCR2121//Japan Science and Technology Agency/ ; //Suntory Rising Stars Encouragement Program in Life Sciences/ ; 20-6102//Toray Science Foundation/ ; }, abstract = {The complex structures of multicellular organisms originate from a unicellular zygote. In most angiosperms, including Arabidopsis thaliana, the zygote is distinctly polar and divides asymmetrically to produce an apical cell, which generates the aboveground part of the plant body, and a basal cell, which generates the root tip and extraembryonic suspensor. Thus, zygote polarity is pivotal for establishing the apical-basal axis running from the shoot apex to the root tip of the plant body. The molecular mechanisms and spatiotemporal dynamics behind zygote polarization remain elusive. However, advances in live-cell imaging of plant zygotes have recently made significant insights possible. In this Cell Science at a Glance article and the accompanying poster, we summarize our understanding of the early steps in apical-basal axis formation in Arabidopsis, with a focus on de novo transcriptional activation after fertilization and the intracellular dynamics leading to the first asymmetric division of the zygote.}, } @article {pmid38424063, year = {2024}, author = {Bayer, EM and Benitez-Alfonso, Y}, title = {Plasmodesmata: Channels Under Pressure.}, journal = {Annual review of plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-arplant-070623-093110}, pmid = {38424063}, issn = {1545-2123}, abstract = {Multicellularity has emerged multiple times in evolution, enabling groups of cells to share a living space and reducing the burden of solitary tasks. While unicellular organisms exhibit individuality and independence, cooperation among cells in multicellular organisms brings specialization and flexibility. However, multicellularity also necessitates intercellular dependence and relies on intercellular communication. In plants, this communication is facilitated by plasmodesmata: intercellular bridges that allow the direct (cytoplasm-to-cytoplasm) transfer of information between cells. Plasmodesmata transport essential molecules that regulate plant growth, development, and stress responses. They are embedded in the extracellular matrix but exhibit flexibility, adapting intercellular flux to meet the plant's needs. In this review, we delve into the formation and functionality of plasmodesmata and examine the capacity of the plant communication network to respond to developmental and environmental cues. We illustrate how environmental pressure shapes cellular interactions and aids the plant in adapting its growth. Expected final online publication date for the Annual Review of Plant Biology, Volume 75 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, } @article {pmid38377113, year = {2024}, author = {Nino Barreat, JG and Katzourakis, A}, title = {Ecological and evolutionary dynamics of cell-virus-virophage systems.}, journal = {PLoS computational biology}, volume = {20}, number = {2}, pages = {e1010925}, pmid = {38377113}, issn = {1553-7358}, mesh = {Humans ; *Virophages ; Apoptosis ; Biological Evolution ; *Coinfection ; Antiviral Agents ; }, abstract = {Microbial eukaryotes, giant viruses and virophages form a unique hyperparasitic system. Virophages are parasites of the virus transcription machinery and can interfere with virus replication, resulting in a benefit to the eukaryotic host population. Surprisingly, virophages can integrate into the genomes of their cell or virus hosts, and have been shown to reactivate during coinfection. This raises questions about the role of integration in the dynamics of cell-virus-virophage systems. We use mathematical models and computational simulations to understand the effect of virophage integration on populations of cells and viruses. We also investigate multicellularity and programmed cell-death (PCD) as potential antiviral defence strategies used by cells. We found that virophages which enter the cell independently of the host virus, such as Mavirus, are expected to integrate commonly into the genomes of their cell hosts. Our models suggest that integrations from virophages without an independent mode of entry like Sputnik, are less likely to become fixed in the cell host population. Alternatively, we found that Sputnik virophages can stably persist integrated in the virus population, as long as they do not completely inhibit virus replication. We also show that increasing virophage inhibition can stabilise oscillatory dynamics, which may explain the long-term persistence of viruses and virophages in the environment. Our results demonstrate that inhibition by virophages and multicellularity are effective antiviral strategies that may act in synergy against viral infection in microbial species.}, } @article {pmid38400751, year = {2024}, author = {Woudenberg, S and Hadid, F and Weijers, D and Borassi, C}, title = {The maternal embrace: the protection of plant embryos.}, journal = {Journal of experimental botany}, volume = {}, number = {}, pages = {}, doi = {10.1093/jxb/erae071}, pmid = {38400751}, issn = {1460-2431}, abstract = {All land plants - the embryophytes - produce multicellular embryos, as other multicellular organisms, such as brown algae and animals. A unique characteristic of plant embryos is their immobile and confined nature. Their embedding in maternal tissues may offer protection from the environment, but also physically constrains development. Across the different land plants, a huge discrepancy is present between their reproductive structures whilst leading to similarly complex embryos. Therefore, we review the roles that maternal tissues play in the control of embryogenesis across land plants. These nurturing, constraining, and protective roles include both direct and indirect effects. In this review, we explore how the maternal surroundings affect embryogenesis and which chemical and mechanical barriers are in place. We regard these questions through the lens of evolution, and identify key questions for future research.}, } @article {pmid38388648, year = {2024}, author = {Ratajczak, MZ and Ratajczak, J}, title = {Leukemogenesis occurs in a microenvironment enriched by extracellular microvesicles/exosomes: recent discoveries and questions to be answered.}, journal = {Leukemia}, volume = {}, number = {}, pages = {}, pmid = {38388648}, issn = {1476-5551}, abstract = {In single-cell organisms, extracellular microvesicles (ExMVs) were one of the first cell-cell communication platforms that emerged very early during evolution. Multicellular organisms subsequently adapted this mechanism. Evidence indicates that all types of cells secrete these small circular structures surrounded by a lipid membrane that may be encrusted by ligands and receptors interacting with target cells and harboring inside a cargo comprising RNA species, proteins, bioactive lipids, signaling nucleotides, and even entire organelles "hijacked" from the cells of origin. ExMVs are secreted by normal cells and at higher levels by malignant cells, and there are some differences in their cargo. On the one hand, ExMVs secreted from malignant cells interact with cells in the microenvironment, and in return, they are exposed by a "two-way mechanism" to ExMVs secreted by non-leukemic cells. Therefore, leukemogenesis occurs and progresses in ExMVs enriched microenvironments, and this biological fact has pathologic, diagnostic, and therapeutic implications. We are still trying to decipher this intriguing cell-cell communication language better. We will present a current point of view on this topic and review some selected most recent discoveries and papers.}, } @article {pmid38386708, year = {2024}, author = {Ilker, E and Hinczewski, M}, title = {Bioenergetic costs and the evolution of noise regulation by microRNAs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {9}, pages = {e2308796121}, doi = {10.1073/pnas.2308796121}, pmid = {38386708}, issn = {1091-6490}, abstract = {Noise control, together with other regulatory functions facilitated by microRNAs (miRNAs), is believed to have played important roles in the evolution of multicellular eukaryotic organisms. miRNAs can dampen protein fluctuations via enhanced degradation of messenger RNA (mRNA), but this requires compensation by increased mRNA transcription to maintain the same expression levels. The overall mechanism is metabolically expensive, leading to questions about how it might have evolved in the first place. We develop a stochastic model of miRNA noise regulation, coupled with a detailed analysis of the associated metabolic costs. Additionally, we calculate binding free energies for a range of miRNA seeds, the short sequences which govern target recognition. We argue that natural selection may have fine-tuned the Michaelis-Menten constant [Formula: see text] describing miRNA-mRNA affinity and show supporting evidence from analysis of experimental data. [Formula: see text] is constrained by seed length, and optimal noise control (minimum protein variance at a given energy cost) is achievable for seeds of 6 to 7 nucleotides in length, the most commonly observed types. Moreover, at optimality, the degree of noise reduction approaches the theoretical bound set by the Wiener-Kolmogorov linear filter. The results illustrate how selective pressure toward energy efficiency has potentially shaped a crucial regulatory pathway in eukaryotes.}, } @article {pmid38385784, year = {2024}, author = {Hesse, E and O'Brien, S}, title = {Ecological dependencies and the illusion of cooperation in microbial communities.}, journal = {Microbiology (Reading, England)}, volume = {170}, number = {2}, pages = {}, doi = {10.1099/mic.0.001442}, pmid = {38385784}, issn = {1465-2080}, abstract = {Ecological dependencies - where organisms rely on other organisms for survival - are a ubiquitous feature of life on earth. Multicellular hosts rely on symbionts to provide essential vitamins and amino acids. Legume plants similarly rely on nitrogen-fixing rhizobia to convert atmospheric nitrogen to ammonia. In some cases, dependencies can arise via loss-of-function mutations that allow one partner to benefit from the actions of another. It is common in microbiology to label ecological dependencies between species as cooperation - making it necessary to invoke cooperation-specific frameworks to explain the phenomenon. However, in many cases, such traits are not (at least initially) cooperative, because they are not selected for because of the benefits they confer on a partner species. In contrast, dependencies in microbial communities may originate from fitness benefits gained from genomic-streamlining (i.e. Black Queen Dynamics). Here, we outline how the Black Queen Hypothesis predicts the formation of metabolic dependencies via loss-of-function mutations in microbial communities, without needing to invoke any cooperation-specific explanations. Furthermore we outline how the Black Queen Hypothesis can act as a blueprint for true cooperation as well as discuss key outstanding questions in the field. The nature of interactions in microbial communities can predict the ability of natural communities to withstand and recover from disturbances. Hence, it is vital to gain a deeper understanding of the factors driving these dynamic interactions over evolutionary time.}, } @article {pmid38382824, year = {2024}, author = {Mikhailovsky, GE}, title = {Life, its definition, origin, evolution, and four-dimensional hierarchical structure.}, journal = {Bio Systems}, volume = {}, number = {}, pages = {105158}, doi = {10.1016/j.biosystems.2024.105158}, pmid = {38382824}, issn = {1872-8324}, abstract = {The main unique features of biological systems are reviewed, and four necessary and sufficient attributes of life are formulated, based on the ideas of Ervin Bauer. The possibility of the occurrence of each of these attributes during the origin of life is analyzed. As a result, different scenarios for the origin of life are presented, with all their pros and cons. Next, the mainstream of biological evolution is discussed, considering it as a special case of general complexification, and structuredness is defined as a quantitative measure of structural complexity. By introducing the concepts of post-dissipative structure and ratcheting process based on "frozen" patterns, their role in the generation of biological structures underlying biological evolution is demonstrated. Furthermore, it is proposed that all living things can be divided into micro- (unicellular) and macro- (multicellular) creatures, which differ from each other even more radically than the difference between prokaryotes and unicellular eukaryotes. Then the fifth, sufficient, but not necessary attribute of life, hierarchicality, is formulated, which is fully applicable only to macrolife. It is also shown that living organisms are primarily chemodynamic rather than thermodynamic systems, and three basic laws of biochemodynamics are formulated. Finally, fifteen basic features of living beings, grouped into four basic blocks, are summarized.}, } @article {pmid38352462, year = {2024}, author = {Kidner, RQ and Goldstone, EB and Laidemitt, MR and Sanchez, MC and Gerdt, C and Brokaw, LP and Ros-Rocher, N and Morris, J and Davidson, WS and Gerdt, JP}, title = {Host lipids regulate multicellular behavior of a predator of a human pathogen.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38352462}, support = {R37 AI101438/AI/NIAID NIH HHS/United States ; T32 GM131994/GM/NIGMS NIH HHS/United States ; S10 OD024988/OD/NIH HHS/United States ; P30 GM110907/GM/NIGMS NIH HHS/United States ; R35 GM138376/GM/NIGMS NIH HHS/United States ; HHSN272201700014C/AI/NIAID NIH HHS/United States ; }, abstract = {As symbionts of animals, microbial eukaryotes benefit and harm their hosts in myriad ways. A model microeukaryote (Capsaspora owczarzaki) is a symbiont of Biomphalaria glabrata snails and may prevent transmission of parasitic schistosomes from snails to humans. However, it is unclear which host factors determine Capsaspora's ability to colonize snails. Here, we discovered that Capsaspora forms multicellular aggregates when exposed to snail hemolymph. We identified a molecular cue for aggregation: a hemolymph-derived phosphatidylcholine, which becomes elevated in schistosome-infected snails. Therefore, Capsaspora aggregation may be a response to the physiological state of its host, and it may determine its ability to colonize snails and exclude parasitic schistosomes. Furthermore, Capsaspora is an evolutionary model organism whose aggregation may be ancestral to animals. This discovery, that a prevalent lipid induces Capsaspora multicellularity, suggests that this aggregation phenotype may be ancient. Additionally, the specific lipid will be a useful tool for further aggregation studies.}, } @article {pmid38375870, year = {2024}, author = {Edelbroek, B and Kjellin, J and Biryukova, I and Liao, Z and Lundberg, T and Noegel, AA and Eichinger, L and Friedländer, MR and Söderbom, F}, title = {Evolution of microRNAs in Amoebozoa and implications for the origin of multicellularity.}, journal = {Nucleic acids research}, volume = {}, number = {}, pages = {}, doi = {10.1093/nar/gkae109}, pmid = {38375870}, issn = {1362-4962}, support = {2021-05793//Swedish Research Council/ ; //Uppsala University/ ; }, abstract = {MicroRNAs (miRNAs) are important and ubiquitous regulators of gene expression in both plants and animals. They are thought to have evolved convergently in these lineages and hypothesized to have played a role in the evolution of multicellularity. In line with this hypothesis, miRNAs have so far only been described in few unicellular eukaryotes. Here, we investigate the presence and evolution of miRNAs in Amoebozoa, focusing on species belonging to Acanthamoeba, Physarum and dictyostelid taxonomic groups, representing a range of unicellular and multicellular lifestyles. miRNAs that adhere to both the stringent plant and animal miRNA criteria were identified in all examined amoebae, expanding the total number of protists harbouring miRNAs from 7 to 15. We found conserved miRNAs between closely related species, but the majority of species feature only unique miRNAs. This shows rapid gain and/or loss of miRNAs in Amoebozoa, further illustrated by a detailed comparison between two evolutionary closely related dictyostelids. Additionally, loss of miRNAs in the Dictyostelium discoideum drnB mutant did not seem to affect multicellular development and, hence, demonstrates that the presence of miRNAs does not appear to be a strict requirement for the transition from uni- to multicellular life.}, } @article {pmid38367762, year = {2024}, author = {Kriete, A}, title = {Dissipative scaling of development and aging in multicellular organisms.}, journal = {Bio Systems}, volume = {}, number = {}, pages = {105157}, doi = {10.1016/j.biosystems.2024.105157}, pmid = {38367762}, issn = {1872-8324}, abstract = {Evolution, self-replication and ontogenesis are highly dynamic, irreversible and self-organizing processes dissipating energy. While progress has been made to decipher the role of thermodynamics in cellular fission, it is not yet clear how entropic balances shape organism growth and aging. This paper derives a general dissipation theory for the life-history of organisms. It implies a self-regulated entropy production facilitating exponential growth within a hierarchical and entropy lowering self-organization. The theory predicts ceilings in energy expenditures imposed by geometric constrains, which promote thermal optimality during development, and a dissipative scaling across organisms consistent with ecological scaling laws combining isometric and allometric terms. The theory also illustrates how growing organisms can tolerate damage through continuous extension and production of new dissipative structures low in entropy. However, when organisms reduce their rate of cell division and reach a steady adult state, they become thermodynamically unstable, increase internal entropy by accumulating damage, and age.}, } @article {pmid38354254, year = {2024}, author = {Doré, H and Eisenberg, AR and Junkins, EN and Leventhal, GE and Ganesh, A and Cordero, OX and Paul, BG and Valentine, DL and O'Malley, MA and Wilbanks, EG}, title = {Targeted hypermutation of putative antigen sensors in multicellular bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {9}, pages = {e2316469121}, doi = {10.1073/pnas.2316469121}, pmid = {38354254}, issn = {1091-6490}, support = {W911NF-19-2-0026//DOD | USA | AFC | CCDC | Army Research Office (ARO)/ ; W911NF-19-D-0001//DOD | USA | AFC | CCDC | Army Research Office (ARO)/ ; 508543//Joint Genome Institute (JGI)/ ; }, mesh = {*Bacteria/genetics ; Archaea/genetics ; Metagenome ; Retroelements ; *Bacteriophages/genetics ; }, abstract = {Diversity-generating retroelements (DGRs) are used by bacteria, archaea, and viruses as a targeted mutagenesis tool. Through error-prone reverse transcription, DGRs introduce random mutations at specific genomic loci, enabling rapid evolution of these targeted genes. However, the function and benefits of DGR-diversified proteins in cellular hosts remain elusive. We find that 82% of DGRs from one of the major monophyletic lineages of DGR reverse transcriptases are encoded by multicellular bacteria, which often have two or more DGR loci in their genomes. Using the multicellular purple sulfur bacterium Thiohalocapsa sp. PB-PSB1 as an example, we characterized nine distinct DGR loci capable of generating 10[282] different combinations of target proteins. With environmental metagenomes from individual Thiohalocapsa aggregates, we show that most of PB-PSB1's DGR target genes are diversified across its biogeographic range, with spatial heterogeneity in the diversity of each locus. In Thiohalocapsa PB-PSB1 and other bacteria hosting this lineage of cellular DGRs, the diversified target genes are associated with NACHT-domain anti-phage defenses and putative ternary conflict systems previously shown to be enriched in multicellular bacteria. We propose that these DGR-diversified targets act as antigen sensors that confer a form of adaptive immunity to their multicellular consortia, though this remains to be experimentally tested. These findings could have implications for understanding the evolution of multicellularity, as the NACHT-domain anti-phage systems and ternary systems share both domain homology and conceptual similarities with the innate immune and programmed cell death pathways of plants and metazoans.}, } @article {pmid38351630, year = {2024}, author = {Iwaï, H and Beyer, HM and Johansson, JEM and Li, M and Wlodawer, A}, title = {The three-dimensional structure of the Vint domain from Tetrahymena thermophila suggests a ligand-regulated cleavage mechanism by the HINT fold.}, journal = {FEBS letters}, volume = {}, number = {}, pages = {}, doi = {10.1002/1873-3468.14817}, pmid = {38351630}, issn = {1873-3468}, support = {75N91019D00024/CA/NCI NIH HHS/United States ; }, abstract = {Vint proteins have been identified in unicellular metazoans as a novel hedgehog-related gene family, merging the von Willebrand factor type A domain and the Hedgehog/INTein (HINT) domains. We present the first three-dimensional structure of the Vint domain from Tetrahymena thermophila corresponding to the auto-processing domain of hedgehog proteins, shedding light on the unique features, including an adduct recognition region (ARR). Our results suggest a potential binding between the ARR and sulfated glycosaminoglycans like heparin sulfate. Moreover, we uncover a possible regulatory role of the ARR in the auto-processing by Vint domains, expanding our understanding of the HINT domain evolution and their use in biotechnological applications. Vint domains might have played a crucial role in the transition from unicellular to multicellular organisms.}, } @article {pmid38334408, year = {2024}, author = {Wang, R and Meng, Q and Wang, X and Xiao, Y and Sun, R and Zhang, Z and Fu, Y and Di Giuseppe, G and Liang, A}, title = {Comparative genomic analysis of symbiotic and free-living Fluviibacter phosphoraccumulans strains provides insights into the evolutionary origins of obligate Euplotes-bacterial endosymbioses.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0190023}, doi = {10.1128/aem.01900-23}, pmid = {38334408}, issn = {1098-5336}, abstract = {Endosymbiosis is a widespread and important phenomenon requiring diverse model systems. Ciliates are a widespread group of protists that often form symbioses with diverse microorganisms. Endosymbioses between the ciliate Euplotes and heritable bacterial symbionts are common in nature, and four essential symbionts were described: Polynucleobacter necessarius, "Candidatus Protistobacter heckmanni," "Ca. Devosia symbiotica," and "Ca. Devosia euplotis." Among them, only the genus Polynucleobacter comprises very close free-living and symbiotic representatives, which makes it an excellent model for investigating symbiont replacements and recent symbioses. In this article, we characterized a novel endosymbiont inhabiting the cytoplasm of Euplotes octocarinatus and found that it is a close relative of the free-living bacterium Fluviibacter phosphoraccumulans (Betaproteobacteria and Rhodocyclales). We present the complete genome sequence and annotation of the symbiotic Fluviibacter. Comparative analyses indicate that the genome of symbiotic Fluviibacter is small in size and rich in pseudogenes when compared with free-living strains, which seems to fit the prediction for recently established endosymbionts undergoing genome erosion. Further comparative analysis revealed reduced metabolic capacities in symbiotic Fluviibacter, which implies that the symbiont relies on the host Euplotes for carbon sources, organic nitrogen and sulfur, and some cofactors. We also estimated substitution rates between symbiotic and free-living Fluviibacter pairs for 233 genes; the results showed that symbiotic Fluviibacter displays higher dN/dS mean value than free-living relatives, which suggested that genetic drift is the main driving force behind molecular evolution in endosymbionts.IMPORTANCEIn the long history of symbiosis research, most studies focused mainly on organelles or bacteria within multicellular hosts. The single-celled protists receive little attention despite harboring an immense diversity of symbiotic associations with bacteria and archaea. One subgroup of the ciliate Euplotes species is strictly dependent on essential symbionts for survival and has emerged as a valuable model for understanding symbiont replacements and recent symbioses. However, almost all of our knowledge about the evolution and functions of Euplotes symbioses comes from the Euplotes-Polynucleobacter system. In this article, we report a novel essential symbiont, which also has very close free-living relatives. Genome analysis indicated that it is a recently established endosymbiont undergoing genome erosion and relies on the Euplotes host for many essential molecules. Our results provide support for the notion that essential symbionts of the ciliate Euplotes evolve from free-living progenitors in the natural water environment.}, } @article {pmid37964233, year = {2023}, author = {Zhang, C and Zhu, Z and Jiang, A and Liu, Q and Chen, M}, title = {Genome-wide identification of the mitogen-activated kinase gene family from Limonium bicolor and functional characterization of LbMAPK2 under salt stress.}, journal = {BMC plant biology}, volume = {23}, number = {1}, pages = {565}, pmid = {37964233}, issn = {1471-2229}, mesh = {*Plumbaginaceae/metabolism ; Mitogens/metabolism ; Salt Stress/genetics ; Mitogen-Activated Protein Kinases/genetics/metabolism ; Stress, Physiological/genetics ; Plant Growth Regulators/metabolism ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/genetics/metabolism ; }, abstract = {BACKGROUND: Mitogen-activated protein kinases (MAPKs) are ubiquitous signal transduction components in eukaryotes. In plants, MAPKs play an essential role in growth and development, phytohormone regulation, and abiotic stress responses. The typical recretohalophyte Limonium bicolor (Bunge) Kuntze has multicellular salt glands on its stems and leaves; these glands secrete excess salt ions from its cells to mitigate salt damage. The number, type, and biological function of L. bicolor MAPK genes are unknown.

RESULTS: We identified 20 candidate L. bicolor MAPK genes, which can be divided into four groups. Of these 20 genes, 17 were anchored to 7 chromosomes, while LbMAPK18, LbMAPK19, and LbMAPK20 mapped to distinct scaffolds. Structure analysis showed that the predicted protein LbMAPK19 contains the special structural motif TNY in its activation loop, whereas the other LbMAPK members harbor the conserved TEY or TDY motif. The promoters of most LbMAPK genes carry cis-acting elements related to growth and development, phytohormones, and abiotic stress. LbMAPK1, LbMAPK2, LbMAPK16, and LbMAPK20 are highly expressed in the early stages of salt gland development, whereas LbMAPK4, LbMAPK5, LbMAPK6, LbMAPK7, LbMAPK11, LbMAPK14, and LbMAPK15 are highly expressed during the late stages. These 20 LbMAPK genes all responded to salt, drought and ABA stress. We explored the function of LbMAPK2 via virus-induced gene silencing: knocking down LbMAPK2 transcript levels in L. bicolor resulted in fewer salt glands, lower salt secretion ability from leaves, and decreased salt tolerance. The expression of several genes [LbTTG1 (TRANSPARENT TESTA OF GL1), LbCPC (CAPRICE), and LbGL2 (GLABRA2)] related to salt gland development was significantly upregulated in LbMAPK2 knockdown lines, while the expression of LbEGL3 (ENHANCER OF GL3) was significantly downregulated.

CONCLUSION: These findings increase our understanding of the LbMAPK gene family and will be useful for in-depth studies of the molecular mechanisms behind salt gland development and salt secretion in L. bicolor. In addition, our analysis lays the foundation for exploring the biological functions of MAPKs in an extreme halophyte.}, } @article {pmid38333966, year = {2024}, author = {Bowles, AMC and Williamson, CJ and Williams, TA and Donoghue, PCJ}, title = {Cryogenian origins of multicellularity in Archaeplastida.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evae026}, pmid = {38333966}, issn = {1759-6653}, abstract = {Earth was impacted by global glaciations during the Cryogenian (720-635 million years ago; Ma), events invoked to explain both the origins of multicellularity in Archaeplastida and radiation of the first land plants. However, the temporal relationship between these environmental and biological events is poorly established, due to a paucity of molecular and fossil data, precluding resolution of the phylogeny and timescale of archaeplastid evolution. We infer a time-calibrated phylogeny of early archaeplastid evolution based on a revised molecular dataset and reappraisal of the fossil record. Phylogenetic topology testing resolves deep archaeplastid relationships, identifying two clades of Viridiplantae and placing Bryopsidales as sister to the Chlorophyceae. Our molecular clock analysis infers an origin of Archaeplastida in the late-Paleoproterozoic to early-Mesoproterozoic (1712-1387 Ma). Ancestral state reconstruction of cytomorphological traits on this time-calibrated tree reveals many of the independent origins of multicellularity span the Cryogenian, consistent with the Cryogenian multicellularity hypothesis. Multicellular rhodophytes emerged 902-655Ma while crown-Anydrophyta (Zygnematophyceae and Embryophyta) originated 796-671Ma, broadly compatible with the Cryogenian plant terrestrialisation hypothesis. Our analyses resolve the timetree of Archaeplastida with age estimates for ancestral multicellular archaeplastids coinciding with the Cryogenian, compatible with hypotheses that propose a role of Snowball Earth in plant evolution.}, } @article {pmid38327154, year = {2024}, author = {Gupta, P and Bermejo-Rodriguez, C and Kocher, H and Pérez-Mancera, PA and Velliou, EG}, title = {Chemotherapy Assessment in Advanced Multicellular 3D Models of Pancreatic Cancer: Unravelling the Importance of Spatiotemporal Mimicry of the Tumor Microenvironment.}, journal = {Advanced biology}, volume = {}, number = {}, pages = {e2300580}, doi = {10.1002/adbi.202300580}, pmid = {38327154}, issn = {2701-0198}, support = {MR/V028553/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is a challenge for global health with very low survival rate and high therapeutic resistance. Hence, advanced preclinical models for treatment screening are of paramount importance. Herein, chemotherapeutic (gemcitabine) assessment on novel (polyurethane) scaffold-based spatially advanced 3D multicellular PDAC models is carried out. Through comprehensive image-based analysis at the protein level, and expression analysis at the mRNA level, the importance of stromal cells is confirmed, primarily activated stellate cells in the chemoresistance of PDAC cells within the models. Furthermore, it is demonstrated that, in addition to the presence of activated stellate cells, the spatial architecture of the scaffolds, i.e., segregation/compartmentalization of the cancer and stromal zones, affect the cellular evolution and is necessary for the development of chemoresistance. These results highlight that, further to multicellularity, mapping the tumor structure/architecture and zonal complexity in 3D cancer models is important for better mimicry of the in vivo therapeutic response.}, } @article {pmid38320549, year = {2024}, author = {Glass, DS and Bren, A and Vaisbourd, E and Mayo, A and Alon, U}, title = {A synthetic differentiation circuit in Escherichia coli for suppressing mutant takeover.}, journal = {Cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cell.2024.01.024}, pmid = {38320549}, issn = {1097-4172}, abstract = {Differentiation is crucial for multicellularity. However, it is inherently susceptible to mutant cells that fail to differentiate. These mutants outcompete normal cells by excessive self-renewal. It remains unclear what mechanisms can resist such mutant expansion. Here, we demonstrate a solution by engineering a synthetic differentiation circuit in Escherichia coli that selects against these mutants via a biphasic fitness strategy. The circuit provides tunable production of synthetic analogs of stem, progenitor, and differentiated cells. It resists mutations by coupling differentiation to the production of an essential enzyme, thereby disadvantaging non-differentiating mutants. The circuit selected for and maintained a positive differentiation rate in long-term evolution. Surprisingly, this rate remained constant across vast changes in growth conditions. We found that transit-amplifying cells (fast-growing progenitors) underlie this environmental robustness. Our results provide insight into the stability of differentiation and demonstrate a powerful method for engineering evolutionarily stable multicellular consortia.}, } @article {pmid38320478, year = {2024}, author = {Donoghue, PCJ and Clark, JW}, title = {Plant evolution: Streptophyte multicellularity, ecology, and the acclimatisation of plants to life on land.}, journal = {Current biology : CB}, volume = {34}, number = {3}, pages = {R86-R89}, doi = {10.1016/j.cub.2023.12.036}, pmid = {38320478}, issn = {1879-0445}, abstract = {Land plants are celebrated as one of the three great instances of complex multicellularity, but new phylogenomic and phenotypic analyses are revealing deep evolutionary roots of multicellularity among algal relatives, prompting questions about the causal basis of this major evolutionary transition.}, } @article {pmid38315855, year = {2024}, author = {Bingham, EP and Ratcliff, WC}, title = {A nonadaptive explanation for macroevolutionary patterns in the evolution of complex multicellularity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {7}, pages = {e2319840121}, doi = {10.1073/pnas.2319840121}, pmid = {38315855}, issn = {1091-6490}, support = {5R35GM138030//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T32GM142616//national research service award (NIH)/ ; DEB-1845363//National Science Foundation (NSF)/ ; }, abstract = {"Complex multicellularity," conventionally defined as large organisms with many specialized cell types, has evolved five times independently in eukaryotes, but never within prokaryotes. A number of hypotheses have been proposed to explain this phenomenon, most of which posit that eukaryotes evolved key traits (e.g., dynamic cytoskeletons, alternative mechanisms of gene regulation, or subcellular compartments) which were a necessary prerequisite for the evolution of complex multicellularity. Here, we propose an alternative, nonadaptive hypothesis for this broad macroevolutionary pattern. By binning cells into groups with finite genetic bottlenecks between generations, the evolution of multicellularity greatly reduces the effective population size (Ne) of cellular populations, increasing the role of genetic drift in evolutionary change. While both prokaryotes and eukaryotes experience this phenomenon, they have opposite responses to drift: eukaryotes tend to undergo genomic expansion, providing additional raw genetic material for subsequent multicellular innovation, while prokaryotes generally face genomic erosion. Taken together, we hypothesize that these idiosyncratic lineage-specific evolutionary dynamics play a fundamental role in the long-term divergent evolution of complex multicellularity across the tree of life.}, } @article {pmid38306281, year = {2024}, author = {Siljestam, M and Martinossi-Allibert, I}, title = {Anisogamy Does Not Always Promote the Evolution of Mating Competition Traits in Males.}, journal = {The American naturalist}, volume = {203}, number = {2}, pages = {230-253}, doi = {10.1086/727968}, pmid = {38306281}, issn = {1537-5323}, mesh = {Male ; Female ; Humans ; *Models, Biological ; *Biological Evolution ; Semen ; Reproduction ; Fertilization ; }, abstract = {AbstractAnisogamy has evolved in most sexually reproducing multicellular organisms allowing the definition of male and female sexes, producing small and large gametes. Anisogamy, as the initial sexual dimorphism, is a good starting point to understand the evolution of further sexual dimorphisms. For instance, it is generally accepted that anisogamy sets the stage for more intense mating competition in males than in females. We argue that this idea stems from a restrictive assumption on the conditions under which anisogamy evolved in the first place: the absence of sperm limitation (assuming that all female gametes are fertilized). Here, we relax this assumption and present a model that considers the coevolution of gamete size with a mating competition trait, starting in a population without dimorphism. We vary gamete density to produce different scenarios of gamete limitation. We show that while at high gamete density the evolution of anisogamy always results in male investment in competition, gamete limitation at intermediate gamete densities allows for either females or males to invest more into mating competition. Our results thus suggest that anisogamy does not always promote mating competition among males. The conditions under which anisogamy evolves matter, as does the competition trait.}, } @article {pmid38301272, year = {2024}, author = {Mihalič, F and Arcila, D and Pettersson, ME and Farkhondehkish, P and Andersson, E and Andersson, L and Betancur-R, R and Jemth, P}, title = {Conservation of affinity rather than sequence underlies a dynamic evolution of the motif-mediated p53/MDM2 interaction in ray-finned fishes.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msae018}, pmid = {38301272}, issn = {1537-1719}, abstract = {The transcription factor and cell cycle regulator p53 is marked for degradation by the ubiquitin ligase MDM2. The interaction between these two proteins is mediated by a conserved binding motif in the disordered p53 transactivation domain (p53TAD) and the folded SWIB domain in MDM2. The conserved motif in p53TAD from zebrafish displays a 20-fold weaker interaction with MDM2, compared to the interaction in human and chicken. To investigate this apparent difference, we tracked the molecular evolution of the p53TAD/MDM2 interaction among ray-finned fishes (Actinopterygii), the largest vertebrate clade. Intriguingly, phylogenetic analyses, ancestral sequence reconstructions, and binding experiments showed that different loss-of-affinity changes in the canonical binding motif within p53TAD have occurred repeatedly and convergently in different fish lineages, resulting in relatively low extant affinities (KD = 0.5-5 μM). However, for eleven different fish p53TAD/MDM2 interactions, non-conserved regions flanking the canonical motif increased the affinity 4 to 73-fold to be on par with the human interaction. Our findings suggest that compensating changes at conserved and non-conserved positions within the motif, as well as in flanking regions of low conservation, underlie a stabilizing selection of "functional affinity" in the p53TAD/MDM2 interaction. Such interplay complicates bioinformatic prediction of binding and call for experimental validation. Motif-mediated protein-protein interactions involving short binding motifs and folded interaction domains are very common across multicellular life. It is likely that evolution of affinity in motif-mediated interactions often involves an interplay between specific interactions made by conserved motif residues and non-specific interactions by non-conserved disordered regions.}, } @article {pmid38277698, year = {2024}, author = {Krämer, U}, title = {Metal Homeostasis in Land Plants: A Perpetual Balancing Act Beyond the Fulfilment of Metalloproteome Cofactor Demands.}, journal = {Annual review of plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-arplant-070623-105324}, pmid = {38277698}, issn = {1545-2123}, abstract = {One of life's decisive innovations was to harness the catalytic power of metals for cellular chemistry. With life's expansion, global atmospheric and biogeochemical cycles underwent dramatic changes. Although initially harmful, they permitted the evolution of multicellularity and the colonization of land. In land plants as primary producers, metal homeostasis faces heightened demands, in part because soil is a challenging environment for nutrient balancing. To avoid both nutrient metal limitation and metal toxicity, plants must maintain the homeostasis of metals within tighter limits than the homeostasis of other minerals. This review describes the present model of protein metalation and sketches its transfer from unicellular organisms to land plants as complex multicellular organisms. The inseparable connection between metal and redox homeostasis increasingly draws our attention to more general regulatory roles of metals. Mineral co-option, the use of nutrient or other metals for functions other than nutrition, is an emerging concept beyond that of nutritional immunity. Expected final online publication date for the Annual Review of Plant Biology, Volume 75 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, } @article {pmid37264144, year = {2024}, author = {Dadras, N and Hasanpur, K and Razeghi, J and Kianianmomeni, A}, title = {Different transcription of novel, functional long non-coding RNA genes by UV-B in green algae, Volvox carteri.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {27}, number = {1}, pages = {213-225}, pmid = {37264144}, issn = {1618-1905}, mesh = {*Volvox/genetics/metabolism ; *RNA, Long Noncoding/genetics/metabolism ; Biological Evolution ; }, abstract = {Long non-coding RNAs (lncRNAs) are identified as important regulatory molecules related to diverse biological processes. In recent years, benefiting from the rapid development of high-throughput sequencing technology, RNA-seq, and analysis methods, more lncRNAs have been identified and discovered in various plant and algal species. However, so far, only limited studies related to algal lncRNAs are available. Volvox carteri f. nagariensis is the best multicellular model organism to study in developmental and evolutionary biology; therefore, studying and increasing information about this species is important. This study identified lncRNAs in the multicellular green algae Volvox carteri and 1457 lncRNAs were reported, using RNA-seq data and with the help of bioinformatics tools and software. This study investigated the effect of low-dose UV-B radiation on changes in the expression profile of lncRNAs in gonidial and somatic cells. The differential expression of lncRNAs was analyzed between the treatment (UV-B) and the control (WL) groups in gonidial and somatic cells. A total of 37 and 26 lncRNAs with significant differential expression in gonidial and somatic cells, respectively, were reported. Co-expression analysis between the lncRNAs and their neighbor protein-coding genes (in the interval of ± 10 Kb) was accomplished. In gonidial cells, 184 genes with a positive correlation and 13 genes with a negative correlation (greater than 0.95), and in somatic cells, 174 genes with a positive correlation, and 18 genes with a negative correlation were detected. Functional analysis of neighboring coding genes was also performed based on gene ontology. The results of the current work may help gain deeper insight into the regulation of gene expression in the studied model organism, Volvox carteri.}, } @article {pmid38271513, year = {2024}, author = {Pennisi, E}, title = {Tiny fossils upend timeline of multicellular life.}, journal = {Science (New York, N.Y.)}, volume = {383}, number = {6681}, pages = {352-353}, doi = {10.1126/science.ado2396}, pmid = {38271513}, issn = {1095-9203}, mesh = {*Fossils ; *Eukaryota ; Biological Evolution ; }, abstract = {Eukaryotes organized into multicellular forms 1.6 billion years ago.}, } @article {pmid38269255, year = {2024}, author = {Briolay, T and Fresquet, J and Meyer, D and Kerfelec, B and Chames, P and Ishow, E and Blanquart, C}, title = {Specific Targeting of Mesothelin-Expressing Malignant Cells Using Nanobody-Functionalized Magneto-Fluorescent Nanoassemblies.}, journal = {International journal of nanomedicine}, volume = {19}, number = {}, pages = {633-650}, pmid = {38269255}, issn = {1178-2013}, mesh = {*Mesothelin ; *Biological Assay ; Cell Line ; Coloring Agents ; Endocytosis ; }, abstract = {INTRODUCTION: Most current anti-cancer therapies are associated with major side effects due to a lack of tumor specificity. Appropriate vectorization of drugs using engineered nanovectors is known to increase local concentration of therapeutic molecules in tumors while minimizing their side effects. Mesothelin (MSLN) is a well-known tumor associated antigen overexpressed in many malignancies, in particular in malignant pleural mesothelioma (MPM), and various MSLN-targeting anticancer therapies are currently evaluated in preclinical and clinical assays. In this study, we described, for the first time, the functionalization of fluorescent organic nanoassemblies (NA) with a nanobody (Nb) targeting MSLN for the specific targeting of MSLN expressing MPM cancer cells.

METHODS: Cell lines from different cancer origin expressing or not MSLN were used. An Nb directed against MSLN was coupled to fluorescent NA using click chemistry. A panel of endocytosis inhibitors was used to study targeted NA internalization by cells. Cancer cells were grown in 2D or 3D and under a flow to evaluate the specificity of the targeted NA. Binding and internalization of the targeted NA were studied using flow cytometry, confocal microscopy and transmission electron microscopy.

RESULTS: We show that the targeted NA specifically bind to MSLN-expressing tumor cells. Moreover, such functionalized NA appear to be internalized more rapidly and in significantly larger proportions compared to naked ones in MSLN+ MPM cells, thereby demonstrating both the functionality and interest of the active targeting strategy. We demonstrated that targeted NA are mainly internalized through a clathrin-independent/dynamin-dependent endocytosis pathway and are directed to lysosomes for degradation. A 3D cell culture model based on MSLN-expressing multicellular tumor spheroids reveals NA penetration in the first superficial layers.

CONCLUSION: Altogether, these results open the path to novel anticancer strategies based on MSLN-activated internalization of NA incorporating drugs to promote specific accumulation of active treatments in tumors.}, } @article {pmid38267842, year = {2024}, author = {Chapman, H and Hsiung, KC and Rawlinson, I and Galimov, ER and Gems, D}, title = {Colony level fitness analysis identifies a trade-off between population growth rate and dauer yield in Caenorhabditis elegans.}, journal = {BMC ecology and evolution}, volume = {24}, number = {1}, pages = {13}, pmid = {38267842}, issn = {2730-7182}, abstract = {BACKGROUND: In the evolution from unicellular to multicellular life forms, natural selection favored reduced cell proliferation and even programmed cell death if this increased organismal fitness. Could reduced individual fertility or even programmed organismal death similarly increase the fitness of colonies of closely-related metazoan organisms? This possibility is at least consistent with evolutionary theory, and has been supported by computer modelling. Caenorhabditis elegans has a boom and bust life history, where populations of nematodes that are sometimes near clonal subsist on and consume food patches, and then generate dauer larva dispersal propagules. A recent study of an in silico model of C. elegans predicted that one determinant of colony fitness (measured as dauer yield) is minimization of futile food consumption (i.e. that which does not contribute to dauer yield). One way to achieve this is to optimize colony population structure by adjustment of individual fertility.

RESULTS: Here we describe development of a C. elegans colony fitness assay, and its use to investigate the effect of altering population structure on colony fitness after population bust. Fitness metrics measured were speed of dauer production, and dauer yield, an indirect measure of efficiency of resource utilization (i.e. conversion of food into dauers). We find that with increasing founder number, speed of dauer production increases (due to earlier bust) but dauer yield rises and falls. In addition, some dauer recovery was detected soon after the post-colony bust peak of dauer yield, suggesting possible bet hedging among dauers.

CONCLUSIONS: These results suggest the presence of a fitness trade-off at colony level between speed and efficiency of resource utilization in C. elegans. They also provide indirect evidence that population structure is a determinant of colony level fitness, potentially by affecting level of futile food consumption.}, } @article {pmid38262417, year = {2024}, author = {Choi, SW and Graf, L and Choi, JW and Jo, J and Boo, GH and Kawai, H and Choi, CG and Xiao, S and Knoll, AH and Andersen, RA and Yoon, HS}, title = {Ordovician origin and subsequent diversification of the brown algae.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2023.12.069}, pmid = {38262417}, issn = {1879-0445}, abstract = {Brown algae are the only group of heterokont protists exhibiting complex multicellularity. Since their origin, brown algae have adapted to various marine habitats, evolving diverse thallus morphologies and gamete types. However, the evolutionary processes behind these transitions remain unclear due to a lack of a robust phylogenetic framework and problems with time estimation. To address these issues, we employed plastid genome data from 138 species, including heterokont algae, red algae, and other red-derived algae. Based on a robust phylogeny and new interpretations of algal fossils, we estimated the geological times for brown algal origin and diversification. The results reveal that brown algae first evolved true multicellularity, with plasmodesmata and reproductive cell differentiation, during the late Ordovician Period (ca. 450 Ma), coinciding with a major diversification of marine fauna (the Great Ordovician Biodiversification Event) and a proliferation of multicellular green algae. Despite its early Paleozoic origin, the diversification of major orders within this brown algal clade accelerated only during the Mesozoic Era, coincident with both Pangea rifting and the diversification of other heterokont algae (e.g., diatoms), coccolithophores, and dinoflagellates, with their red algal-derived plastids. The transition from ancestral isogamy to oogamy was followed by three simultaneous reappearances of isogamy during the Cretaceous Period. These are concordant with a positive character correlation between parthenogenesis and isogamy. Our new brown algal timeline, combined with a knowledge of past environmental conditions, shed new light on brown algal diversification and the intertwined evolution of multicellularity and sexual reproduction.}, } @article {pmid38255007, year = {2024}, author = {Gazzellone, A and Sangiorgi, E}, title = {From Churchill to Elephants: The Role of Protective Genes against Cancer.}, journal = {Genes}, volume = {15}, number = {1}, pages = {}, doi = {10.3390/genes15010118}, pmid = {38255007}, issn = {2073-4425}, abstract = {Richard Peto's paradox, first described in 1975 from an epidemiological perspective, established an inverse correlation between the probability of developing cancer in multicellular organisms and the number of cells. Larger animals exhibit fewer tumors compared to smaller ones, though exceptions exist. Mice are more susceptible to cancer than humans, while elephants and whales demonstrate significantly lower cancer prevalence rates than humans. How nature and evolution have addressed the issue of cancer in the animal kingdom remains largely unexplored. In the field of medicine, much attention has been devoted to cancer-predisposing genes, as they offer avenues for intervention, including blocking, downregulating, early diagnosis, and targeted treatment. Predisposing genes also tend to manifest clinically earlier and more aggressively, making them easier to identify. However, despite significant strides in modern medicine, the role of protective genes lags behind. Identifying genes with a mild predisposing effect poses a significant challenge. Consequently, comprehending the protective function conferred by genes becomes even more elusive, and their very existence is subject to questioning. While the role of variable expressivity and penetrance defects of the same variant in a family is well-documented for many hereditary cancer syndromes, attempts to delineate the function of protective/modifier alleles have been restricted to a few instances. In this review, we endeavor to elucidate the role of protective genes observed in the animal kingdom, within certain genetic syndromes that appear to act as cancer-resistant/repressor alleles. Additionally, we explore the role of protective alleles in conditions predisposing to cancer. The ultimate goal is to discern why individuals, like Winston Churchill, managed to live up to 91 years of age, despite engaging in minimal physical activity, consuming large quantities of alcohol daily, and not abstaining from smoking.}, } @article {pmid38244715, year = {2024}, author = {Skene, KR}, title = {Systems theory, thermodynamics and life: Integrated thinking across ecology, organization and biological evolution.}, journal = {Bio Systems}, volume = {236}, number = {}, pages = {105123}, doi = {10.1016/j.biosystems.2024.105123}, pmid = {38244715}, issn = {1872-8324}, abstract = {In this paper we explore the relevance and integration of system theory and thermodynamics in terms of the Earth system. It is proposed that together, these fields explain the evolution, organization, functionality and directionality of life on Earth. We begin by summarizing historical and current thinking on the definition of life itself. We then investigate the evidence for a single unit of life. Given that any definition of life and its levels of organization are intertwined, we explore how the Earth system is structured and functions from an energetic perspective, by outlining relevant thermodynamic theory relating to molecular, metabolic, cellular, individual, population, species, ecosystem and biome organization. We next investigate the fundamental relationships between systems theory and thermodynamics in terms of the Earth system, examining the key characteristics of self-assembly, self-organization (including autonomy), emergence, non-linearity, feedback and sub-optimality. Finally, we examine the relevance of systems theory and thermodynamics with reference to two specific aspects: the tempo and directionality of evolution and the directional and predictable process of ecological succession. We discuss the importance of the entropic drive in understanding altruism, multicellularity, mutualistic and antagonistic relationships and how maximum entropy production theory may explain patterns thought to evidence the intermediate disturbance hypothesis.}, } @article {pmid38230926, year = {2024}, author = {Corrales, J and Ramos-Alonso, L and González-Sabín, J and Ríos-Lombardía, N and Trevijano-Contador, N and Engen Berg, H and Sved Skottvoll, F and Moris, F and Zaragoza, O and Chymkowitch, P and Garcia, I and Enserink, JM}, title = {Characterization of a selective, iron-chelating antifungal compound that disrupts fungal metabolism and synergizes with fluconazole.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0259423}, doi = {10.1128/spectrum.02594-23}, pmid = {38230926}, issn = {2165-0497}, abstract = {Fungal infections are a growing global health concern due to the limited number of available antifungal therapies as well as the emergence of fungi that are resistant to first-line antimicrobials, particularly azoles and echinocandins. Development of novel, selective antifungal therapies is challenging due to similarities between fungal and mammalian cells. An attractive source of potential antifungal treatments is provided by ecological niches co-inhabited by bacteria, fungi, and multicellular organisms, where complex relationships between multiple organisms have resulted in evolution of a wide variety of selective antimicrobials. Here, we characterized several analogs of one such natural compound, collismycin A. We show that NR-6226C has antifungal activity against several pathogenic Candida species, including C. albicans and C. glabrata, whereas it only has little toxicity against mammalian cells. Mechanistically, NR-6226C selectively chelates iron, which is a limiting factor for pathogenic fungi during infection. As a result, NR-6226C treatment causes severe mitochondrial dysfunction, leading to formation of reactive oxygen species, metabolic reprogramming, and a severe reduction in ATP levels. Using an in vivo model for fungal infections, we show that NR-6226C significantly increases survival of Candida-infected Galleria mellonella larvae. Finally, our data indicate that NR-6226C synergizes strongly with fluconazole in inhibition of C. albicans. Taken together, NR-6226C is a promising antifungal compound that acts by chelating iron and disrupting mitochondrial functions.IMPORTANCEDrug-resistant fungal infections are an emerging global threat, and pan-resistance to current antifungal therapies is an increasing problem. Clearly, there is a need for new antifungal drugs. In this study, we characterized a novel antifungal agent, the collismycin analog NR-6226C. NR-6226C has a favorable toxicity profile for human cells, which is essential for further clinical development. We unraveled the mechanism of action of NR-6226C and found that it disrupts iron homeostasis and thereby depletes fungal cells of energy. Importantly, NR-6226C strongly potentiates the antifungal activity of fluconazole, thereby providing inroads for combination therapy that may reduce or prevent azole resistance. Thus, NR-6226C is a promising compound for further development into antifungal treatment.}, } @article {pmid38244543, year = {2024}, author = {Bierenbroodspot, MJ and Darienko, T and de Vries, S and Fürst-Jansen, JMR and Buschmann, H and Pröschold, T and Irisarri, I and de Vries, J}, title = {Phylogenomic insights into the first multicellular streptophyte.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2023.12.070}, pmid = {38244543}, issn = {1879-0445}, abstract = {Streptophytes are best known as the clade containing the teeming diversity of embryophytes (land plants).[1][,][2][,][3][,][4] Next to embryophytes are however a range of freshwater and terrestrial algae that bear important information on the emergence of key traits of land plants. Among these, the Klebsormidiophyceae stand out. Thriving in diverse environments-from mundane (ubiquitous occurrence on tree barks and rocks) to extreme (from the Atacama Desert to the Antarctic)-Klebsormidiophyceae can exhibit filamentous body plans and display remarkable resilience as colonizers of terrestrial habitats.[5][,][6] Currently, the lack of a robust phylogenetic framework for the Klebsormidiophyceae hampers our understanding of the evolutionary history of these key traits. Here, we conducted a phylogenomic analysis utilizing advanced models that can counteract systematic biases. We sequenced 24 new transcriptomes of Klebsormidiophyceae and combined them with 14 previously published genomic and transcriptomic datasets. Using an analysis built on 845 loci and sophisticated mixture models, we establish a phylogenomic framework, dividing the six distinct genera of Klebsormidiophyceae in a novel three-order system, with a deep divergence more than 830 million years ago. Our reconstructions of ancestral states suggest (1) an evolutionary history of multiple transitions between terrestrial-aquatic habitats, with stem Klebsormidiales having conquered land earlier than embryophytes, and (2) that the body plan of the last common ancestor of Klebsormidiophyceae was multicellular, with a high probability that it was filamentous whereas the sarcinoids and unicells in Klebsormidiophyceae are likely derived states. We provide evidence that the first multicellular streptophytes likely lived about a billion years ago.}, } @article {pmid38205032, year = {2024}, author = {Nakamura, YT and Himeoka, Y and Saito, N and Furusawa, C}, title = {Evolution of hierarchy and irreversibility in theoretical cell differentiation model.}, journal = {PNAS nexus}, volume = {3}, number = {1}, pages = {pgad454}, pmid = {38205032}, issn = {2752-6542}, abstract = {The process of cell differentiation in multicellular organisms is characterized by hierarchy and irreversibility in many cases. However, the conditions and selection pressures that give rise to these characteristics remain poorly understood. By using a mathematical model, here we show that the network of differentiation potency (differentiation diagram) becomes necessarily hierarchical and irreversible by increasing the number of terminally differentiated states under certain conditions. The mechanisms generating these characteristics are clarified using geometry in the cell state space. The results demonstrate that the hierarchical organization and irreversibility can manifest independently of direct selection pressures associated with these characteristics, instead they appear to evolve as byproducts of selective forces favoring a diversity of differentiated cell types. The study also provides a new perspective on the structure of gene regulatory networks that produce hierarchical and irreversible differentiation diagrams. These results indicate some constraints on cell differentiation, which are expected to provide a starting point for theoretical discussion of the implicit limits and directions of evolution in multicellular organisms.}, } @article {pmid38196363, year = {2024}, author = {Howe, J and Cornwallis, CK and Griffin, AS}, title = {Conflict-reducing innovations in development enable increased multicellular complexity.}, journal = {Proceedings. Biological sciences}, volume = {291}, number = {2014}, pages = {20232466}, pmid = {38196363}, issn = {1471-2954}, mesh = {Animals ; Phylogeny ; *Cognition ; Cell Division ; *Stem Cells ; }, abstract = {Obligately multicellular organisms, where cells can only reproduce as part of the group, have evolved multiple times across the tree of life. Obligate multicellularity has only evolved when clonal groups form by cell division, rather than by cells aggregating, as clonality prevents internal conflict. Yet obligately multicellular organisms still vary greatly in 'multicellular complexity' (the number of cells and cell types): some comprise a few cells and cell types, while others have billions of cells and thousands of types. Here, we test whether variation in multicellular complexity is explained by two conflict-suppressing mechanisms, namely a single-cell bottleneck at the start of development, and a strict separation of germline and somatic cells. Examining the life cycles of 129 lineages of plants, animals, fungi and algae, we show using phylogenetic comparative analyses that an early segregation of the germline stem-cell lineage is key to the evolution of more cell types, driven by a strong correlation in the Metazoa. By contrast, the presence of a strict single-cell bottleneck was not related to either the number of cells or the number of cell types, but was associated with early germline segregation. Our results suggest that segregating the germline earlier in development enabled greater evolutionary innovation, although whether this is a consequence of conflict reduction or other non-conflict effects, such as developmental flexibility, is unclear.}, } @article {pmid38196360, year = {2024}, author = {Pequeno, PACL}, title = {Resource adaptation drives the size-complexity rule in termites.}, journal = {Proceedings. Biological sciences}, volume = {291}, number = {2014}, pages = {20232363}, doi = {10.1098/rspb.2023.2363}, pmid = {38196360}, issn = {1471-2954}, abstract = {The size-complexity rule posits that the evolution of larger cooperative groups should favour more division of labour. Examples include more cell types in larger multicellular organisms, and more polymorphic castes in larger eusocial colonies. However, a correlation between division of labour and group size may reflect a shared response of both traits to resource availability and/or profitability. Here, this possibility was addressed by investigating the evolution of sterile caste number (worker and soldier morphotypes) in termites, a major clade of eusocial insects in which the drivers of caste polymorphism are poorly understood. A novel dataset on 90 termite species was compiled from the published literature. The analysis showed that sterile caste number did increase markedly with colony size. However, after controlling for resource adaptations and phylogeny, there was no evidence for this relationship. Rather, sterile caste number increased with increasing nest-food separation and decreased with soil-feeding, through changes in worker (but not soldier) morphotype number. Further, colony size increased with nest-food separation, thus driving the false correlation between sterile caste number and colony size. These findings support adaptation to higher energy acquisition as key to the rise of complex insect societies, with larger size being a by-product.}, } @article {pmid38194907, year = {2024}, author = {Hall, R and Bandara, A and Charlebois, D}, title = {Fitness effects of a demography-dispersal trade-off in expandingSaccharomyces cerevisiaemats.}, journal = {Physical biology}, volume = {}, number = {}, pages = {}, doi = {10.1088/1478-3975/ad1ccd}, pmid = {38194907}, issn = {1478-3975}, abstract = {Fungi expand in space and time to form complex multicellular communities. The mechanisms by which they do so can vary dramatically and determine the life-history and dispersal traits of expanding populations. These traits influence deterministic and stochastic components of evolution, resulting in complex eco-evolutionary dynamics during colony expansion. We perform experiments on budding yeast strains genetically-engineered to display rough-surface and smooth-surface phenotypes in colony-like structures called ``mats''. Previously, it was shown that the rough-surface strain has a competitive advantage over the smooth-surface strain when grown on semi-solid media. We experimentally observe the emergence and expansion of segments with a distinct smooth-surface phenotype during rough-surface mat development. We propose a trade-off between dispersal and local carrying capacity to explain the relative fitness of these two phenotypes. Using a modified stepping-stone model, we demonstrate that this trade-off gives the high-dispersing, rough-surface phenotype a competitive advantage from standing variation, but that it inhibits this phenotype's ability to invade a resident smooth-surface population via mutation. However, the trade-off improves the ability of the smooth-surface phenotype to invade in rough-surface mats, replicating the frequent emergence of smooth-surface segments in experiments. Together, these computational and experimental findings advance our understanding of the complex eco-evolutionary dynamics of fungal mat expansion.}, } @article {pmid38192262, year = {2024}, author = {Schuster, CD and Salvatore, F and Moens, L and Martí, MA}, title = {Globin phylogeny, evolution and function, the newest update.}, journal = {Proteins}, volume = {}, number = {}, pages = {}, doi = {10.1002/prot.26659}, pmid = {38192262}, issn = {1097-0134}, abstract = {Our globin census update allows us to refine our vision of globin origin, evolution, and structure to function relationship in the context of the currently accepted tree of life. The modern globin domain originates as a single domain, three-over-three α-helical folded structure before the diversification of the kingdoms of life (Bacteria, Archaea, Eukarya). Together with the diversification of prokaryotes, three monophyletic globin families (M, S, and T) emerged, most likely in Proteobacteria and Actinobacteria, displaying specific sequence and structural features, and spread by vertical and horizontal gene transfer, most probably already present in the last universal common ancestor (LUCA). Non-globin domains were added, and eventually lost again, creating multi-domain structures in key branches of M- (FHb and Adgb) and the vast majority of S globins, which with their coevolved multi-domain architectures, have predominantly "sensor" functions. Single domain T-family globins diverged into four major groups and most likely display functions related to reactive nitrogen and oxygen species (RNOS) chemistry, as well as oxygen storage/transport which drives the evolution of its major branches with their characteristic key distal residues (B10, E11, E7, and G8). M-family evolution also lead to distinctive major types (FHb and Fgb, Ngb, Adgb, GbX vertebrate Gbs), and shows the shift from high oxygen affinity controlled by TyrB10-Gln/AsnE11 likely related to RNOS chemistry in microorganisms, to a moderate oxygen affinity storage/transport function controlled by hydrophobic B10/E11-HisE7 in multicellular animals.}, } @article {pmid38190361, year = {2024}, author = {Petreš, M and Loc, M and Budakov, D and Dudaš, T and Stojšin, V and Stankov Petreš, A and Grahovac, M}, title = {First report of brown spot on stored apple fruits caused by Stemphylium vesicarium in Serbia.}, journal = {Plant disease}, volume = {}, number = {}, pages = {}, doi = {10.1094/PDIS-10-23-2131-PDN}, pmid = {38190361}, issn = {0191-2917}, abstract = {Apple is one of the most economically important fruit crops worldwide, and fungal postharvest diseases can cause significant losses during storage (Petreš et al. 2020). Apple fruits (cultivar Fuji) with necrosis symptoms were collected during the fall of 2022 from the cold storage facility (ULO - Ultra Low Oxygen) in Titel, Serbia. The fruits originated from the apple orchard in Titel, Serbia (45°12'47.1"N, 20°15'23.6"E). The pathogens were isolated from collected fruit samples using standard phytopathological techniques. Fruits were surface-sterilized, rinsed with sterile water, aseptically cut in half, and small fragments collected from the border of healthy and diseased tissue were placed into Petri dishes on Potato Dextrose Agar medium (PDA) and incubated at 25±1 °C in dark for seven days. The obtained 11 isolates were identified to the genus level as Alternaria (incidence 46%), Penicillium (36%), Fusarium (9%) and Stemphylium (9%) based on morphological characteristics. Pathogenicity of all isolates was confirmed on apple fruits of cultivars Fuji and Golden Delicious. The fruits were surface-sterilized, sprayed with 5 ml conidial suspension (1×10[5] conidia/ml) and incubated at room temperature for 21 days. Symptoms developed on inoculated fruits were the same as symptoms observed on apple fruit samples collected from cold storage. Reisolation from artificially inoculated fruits resulted in colonies that morphologically corresponded with the colonies used for inoculation. Stemphylium isolate was the only one included in further research. Initial symptoms and symptoms on artificially inoculated apple fruits caused by Stemphylium sp. occurred as circular dark brown necrosis located near the calyx, without visible sporulation on the fruit surface. The isolate and reisolate formed aerial, white to light brown mycelia. The pigmentation of the culture medium was pale to dark brown. Conidia were singular, cylindrical and multicellular, brown to dark brown, 22-35.1 long and 12.6-18.9 μm wide. Based on morphological properties, isolate and reisolate were identified as Stemphylium vesicarium which is in line with the description reported by Sharifi et al. (2021) and Gilardi et al. (2022). The identification of S. vesicarium isolate was confirmed by polymerase chain reaction (PCR) by amplifying and sequencing three regions using following primer pairs: Bt2a (5'- GGT AAC CAA ATC GGT GCT GCT TTC -3') and Bt2b (5'-ACC CTC AGT GTA GTG ACC CTT GGC-3') for β-tubulin region (Nasri et al. 2015), ITS1 (5'-TCC GTA GGT GAA CCT GCG G - 3') and ITS4 (5'- TCC TCC GCT TAT TGA TAT GC-3') for ITS region (White et al. 1990), and EF1 (5' - ATG GGT AAG GAG GAC AAG AC - 3') and EF2 (5'- GGA AGT ACC AGT GAT CAT GTT - 3') for TEF-1α region (O'Donnell et al. 1998). PCR products were separated by horizontal gel electrophoresis in 1.5% agarose gel, stained with ethidium bromide, and visualization under UV light revealed amplified fragments of the expected size of 500 bp for Bt2a/ Bt2b primer pair, 600 bp for ITS1/ITS4 primer pair, and 700 bp for EF1/EF2 primer pair. The obtained amplicons were Sanger sequenced (Macrogen Europe BV) in both directions. BLASTn analysis showed the identity of amplified fragments of the isolates with sequences of S. vesicarium present in the GenBank of 100% (MT881940.1 and JQ671944.1) for the β-tubulin region, 99.40% (MT520589.1 and OR256793.1) for the ITS region, and 99.49% (DQ471090.2 and MT394642.1) for the TEF-1α region. The sequences were deposited to NCBI GenBank (Accession No. OQ653540 for the β-tubulin region, OQ678016 for the ITS region, and OR232710 for the TEF-1α region). To our knowledge, this is the first finding of S. vesicarium on apple fruits in the Republic of Serbia, and the finding of a new causal agent of postharvest apple fruit rot.}, } @article {pmid38185860, year = {2024}, author = {Roggenbuck, EC and Hall, EA and Hanson, IB and Roby, AA and Zhang, KK and Alkatib, KA and Carter, JA and Clewner, JE and Gelfius, AL and Gong, S and Gordon, FR and Iseler, JN and Kotapati, S and Li, M and Maysun, A and McCormick, EO and Rastogi, G and Sengupta, S and Uzoma, CU and Wolkov, MA and Clowney, EJ}, title = {Let's talk about sex: Mechanisms of neural sexual differentiation in Bilateria.}, journal = {WIREs mechanisms of disease}, volume = {}, number = {}, pages = {e1636}, doi = {10.1002/wsbm.1636}, pmid = {38185860}, issn = {2692-9368}, support = {//McKnight Scholar Award/ ; //Pew Biomedical Scholar Award/ ; //Rita Allen Foundation Scholar Award/ ; }, abstract = {In multicellular organisms, sexed gonads have evolved that facilitate release of sperm versus eggs, and bilaterian animals purposefully combine their gametes via mating behaviors. Distinct neural circuits have evolved that control these physically different mating events for animals producing eggs from ovaries versus sperm from testis. In this review, we will describe the developmental mechanisms that sexually differentiate neural circuits across three major clades of bilaterian animals-Ecdysozoa, Deuterosomia, and Lophotrochozoa. While many of the mechanisms inducing somatic and neuronal sex differentiation across these diverse organisms are clade-specific rather than evolutionarily conserved, we develop a common framework for considering the developmental logic of these events and the types of neuronal differences that produce sex-differentiated behaviors. This article is categorized under: Congenital Diseases > Stem Cells and Development Neurological Diseases > Stem Cells and Development.}, } @article {pmid38181075, year = {2024}, author = {Qi, Z and Lu, P and Long, X and Cao, X and Wu, M and Xin, K and Xue, T and Gao, X and Huang, Y and Wang, Q and Jiang, C and Xu, JR and Liu, H}, title = {Adaptive advantages of restorative RNA editing in fungi for resolving survival-reproduction trade-offs.}, journal = {Science advances}, volume = {10}, number = {1}, pages = {eadk6130}, doi = {10.1126/sciadv.adk6130}, pmid = {38181075}, issn = {2375-2548}, mesh = {*Codon, Nonsense ; RNA Editing/genetics ; Amino Acids ; *Magnoliopsida ; Reproduction ; }, abstract = {RNA editing in various organisms commonly restores RNA sequences to their ancestral state, but its adaptive advantages are debated. In fungi, restorative editing corrects premature stop codons in pseudogenes specifically during sexual reproduction. We characterized 71 pseudogenes and their restorative editing in Fusarium graminearum, demonstrating that restorative editing of 16 pseudogenes is crucial for germ tissue development in fruiting bodies. Our results also revealed that the emergence of premature stop codons is facilitated by restorative editing and that premature stop codons corrected by restorative editing are selectively favored over ancestral amino acid codons. Furthermore, we found that ancestral versions of pseudogenes have antagonistic effects on reproduction and survival. Restorative editing eliminates the survival costs of reproduction caused by antagonistic pleiotropy and provides a selective advantage in fungi. Our findings highlight the importance of restorative editing in the evolution of fungal complex multicellularity and provide empirical evidence that restorative editing serves as an adaptive mechanism enabling the resolution of genetic trade-offs.}, } @article {pmid38175037, year = {2024}, author = {Lyman, GH and Lyman, CH and Kuderer, NM}, title = {THE NATURE, ORIGIN, AND EVOLUTION OF LIFE: Part IV Cellular Differentiation and the Emergence of Multicellular Life.}, journal = {Cancer investigation}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/07357907.2024.2302201}, pmid = {38175037}, issn = {1532-4192}, } @article {pmid38154271, year = {2023}, author = {Kong, Z and Zhu, L and Liu, Y and Liu, Y and Chen, G and Jiang, T and Wang, H}, title = {Effects of azithromycin exposure during pregnancy at different stages, doses and courses on testicular development in fetal mice.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {170}, number = {}, pages = {116063}, doi = {10.1016/j.biopha.2023.116063}, pmid = {38154271}, issn = {1950-6007}, abstract = {Azithromycin is a commonly used antibiotic during pregnancy, but some studies have suggested its potential developmental toxicity. Currently, the effects and mechanisms of prenatal azithromycin exposure (PAzE) on fetal testicular development are still unclear. The effects of prenatal exposure to the same drug on fetal testicular development could vary depending on different stages, doses, and courses. Hence, in this study, based on clinical medication characteristics, Kunming mice was administered intragastrically with azithromycin at different stages (mid-/late-pregnancy), doses (50, 100, 200 mg/kg·d), and courses (single-/multi-course). Fetal blood and testicular samples were collected on GD18 for relevant assessments. The results indicated that PAzE led to changes in fetal testicular morphology, reduced cell proliferation, increased apoptosis, and decreased expression of markers related to Leydig cells (Star), Sertoli cells (Wt1), and spermatogonia (Plzf). Further investigation revealed that the effects of PAzE on fetal testicular development were characterized by mid-pregnancy, high dose (clinical dose), and single course having more pronounced effects. Additionally, the TGFβ/Smad and Nrf2 signaling pathways may be involved in the changes in fetal testicular development induced by PAzE. In summary, this study confirmed that PAzE influences fetal testicular morphological development and multicellular function. It provided theoretical and experimental evidence for guiding the rational use of azithromycin during pregnancy and further exploring the mechanisms underlying its developmental toxicity on fetal testicles.}, } @article {pmid38151680, year = {2023}, author = {Bich, L}, title = {Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.}, journal = {Acta biotheoretica}, volume = {72}, number = {1}, pages = {1}, pmid = {38151680}, issn = {1572-8358}, mesh = {Animals ; *Biological Evolution ; *Biofilms ; }, abstract = {This paper focuses on physiological integration in multicellular systems, a notion often associated with biological individuality, but which has not received enough attention and needs a thorough theoretical treatment. Broadly speaking, physiological integration consists in how different components come together into a cohesive unit in which they are dependent on one another for their existence and activity. This paper argues that physiological integration can be understood by considering how the components of a biological multicellular system are controlled and coordinated in such a way that their activities can contribute to the maintenance of the system. The main implication of this perspective is that different ways of controlling their parts may give rise to multicellular organizations with different degrees of integration. After defining control, this paper analyses how control is realized in two examples of multicellular systems located at different ends of the spectrum of multicellularity: biofilms and animals. It focuses on differences in control ranges, and it argues that a high degree of integration implies control exerted at both medium and long ranges, and that insofar as biofilms lack long-range control (relative to their size) they can be considered as less integrated than other multicellular systems. It then discusses the implication of this account for the debate on physiological individuality and the idea that degrees of physiological integration imply degrees of individuality.}, } @article {pmid38144124, year = {2023}, author = {Wu, W and Yang, R and Liu, J and Wang, Z and Li, S and Shao, Y and Deng, Y and Ye, T and Luo, C and Gao, L and Chen, J and Ren, H and Yang, C and Li, J and Wan, D and Tai, W}, title = {Origins of the Ediacaran Doushantuo High-Grade Primary Phosphorites at Kaiyang, Guizhou Province, China.}, journal = {ACS omega}, volume = {8}, number = {50}, pages = {47938-47953}, pmid = {38144124}, issn = {2470-1343}, abstract = {The Ediacaran Doushantuo phosphate deposit in Kaiyang, Guizhou Province, China, contains thick phosphate ores. Most of the ores are reconstituted phosphorite, and there have been few studies of the primary phosphorites, which has led to controversy regarding the origins and nature of mineralization of these phosphate-rich deposits. We identified high-grade primary phosphorites in the Kaiyang area and undertook a stratigraphic, petrological, sedimentological, geochemical, and isotopic study of these rocks. Moving up-section, the Longshui phosphate ore deposit comprises granular, micritic, stromatolitic, honeycomb, and sandy phosphorites. The first four types of phosphorite contain abundant biological structures, such as spherical, lobe-like, and amorphous forms. These are mainly fossils of benthic multicellular red algae, along with other types of algae. These fossils comprise >70% of the phosphorites, indicating that these are protist phosphorites. The ores are massive, unstratified, and contain numerous layered cavity structures, indicating that the ore bed was originally a reef. The phosphorites have P2O5 contents of 38.6-40.2 wt %, with an average of 38.9 wt %. The Al2O3 + TiO2 values are 0.02-0.44 wt %. The δ[18]O values of the samples vary from 13.76 to 16.57‰, with an average of 14.60‰, and δ[13]C values range from -15.789 to -8.697‰, with an average of -13.133‰. The samples exhibit rare-earth element patterns that are enriched with middle rare-earth elements and have strongly negative Ce anomalies. The geochemical features show that the reef was deposited in clear and oxidized waters. The discovery of this high-grade protist phosphorite shows that the involvement of algae was key to the formation of the Kaiyang phosphate-rich deposit.}, } @article {pmid37596740, year = {2023}, author = {Pinion, AK and Britz, R and Kubicek, KM and Siegel, DS and Conway, KW}, title = {The larval attachment organ of the bowfin Amia ocellicauda Richardson, 1836 (Amiiformes: Amiidae) and its phylogenetic significance.}, journal = {Journal of fish biology}, volume = {103}, number = {6}, pages = {1300-1311}, doi = {10.1111/jfb.15528}, pmid = {37596740}, issn = {1095-8649}, support = {HATCH TEX09452//Texas A&M Agrilife Research/ ; NSFDBI2035082//US National Science Foundation/ ; }, mesh = {Animals ; Larva ; Phylogeny ; *Fishes ; Microscopy, Electron, Scanning ; }, abstract = {Larval attachment organs (LAOs) are unicellular or multicellular organs that enable the larvae of many actinopterygian fishes to adhere to a substrate before yolk-sac absorption and the free-swimming stage. Bowfins (Amiiformes) exhibit a sizable LAO on the snout, which was first described in the late 19th and early 20th centuries. In this study, we document the LAO of Amia ocellicauda (Richardson, 1836) using a combination of scanning electron microscopy (SEM) and light microscopy, and histochemistry. We examined material representing three stages with SEM ranging in size from 5.8 to 11.2 mm in notochord length and one stage histochemically. We compare the LAO of A. ocellicauda to that of the lepisosteid Atractosteus tropicus Gill, 1863 and show that although the LAOs of A. ocellicauda and A. tropicus are both super-organs, the two differ in the ultrastructure of the entire organ. A. ocellicauda possesses two distinct lobes, with the organs arranged on the periphery with none in the middle, whereas A. tropicus also possesses two lobes, but with the organs scattered evenly across the super-organ. The individual organs of A. ocellicauda possess adhesive cells set deep to support cells with the adhesive substance released through a pore, whereas A. tropicus possesses both support cells and adhesive cells sitting at a similar level, with the adhesive substance released directly onto the surface of the organ. We additionally provide a table summarizing vertebrate genera in which attachment organs have been documented and discuss the implications of our study for hypotheses of the homology of attachment organs in the Holostei.}, } @article {pmid38110826, year = {2023}, author = {Kotarska, K and Gąsior, Ł and Rudnicka, J and Polański, Z}, title = {Long-run real-time PCR analysis of repetitive nuclear elements as a novel tool for DNA damage quantification in single cells: an approach validated on mouse oocytes and fibroblasts.}, journal = {Journal of applied genetics}, volume = {}, number = {}, pages = {}, pmid = {38110826}, issn = {2190-3883}, support = {2019/03/X/NZ3/00572//Narodowe Centrum Nauki/ ; }, abstract = {Since DNA damage is of great importance in various biological processes, its rate is frequently assessed both in research studies and in medical diagnostics. The most precise methods of quantifying DNA damage are based on real-time PCR. However, in the conventional version, they require a large amount of genetic material and therefore their usefulness is limited to multicellular samples. Here, we present a novel approach to long-run real-time PCR-based DNA-damage quantification (L1-LORD-Q), which consists in amplification of long interspersed nuclear elements (L1) and allows for analysis of single-cell genomes. The L1-LORD-Q was compared with alternative methods of measuring DNA breaks (Bioanalyzer system, γ-H2AX foci staining), which confirmed its accuracy. Furthermore, it was demonstrated that the L1-LORD-Q is sensitive enough to distinguish between different levels of UV-induced DNA damage. The method was validated on mouse oocytes and fibroblasts, but the general idea is universal and can be applied to various types of cells and species.}, } @article {pmid38106219, year = {2023}, author = {Wong, W and Bravo, P and Yunker, PJ and Ratcliff, WC and Burnetti, AJ}, title = {Examining the role of oxygen-binding proteins on the early evolution of multicellularity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.12.01.569647}, pmid = {38106219}, abstract = {Oxygen availability is a key factor in the evolution of multicellularity, as larger and more sophisticated organisms often require mechanisms allowing efficient oxygen delivery to their tissues. One such mechanism is the presence of oxygen-binding proteins, such as globins and hemerythrins, which arose in the ancestor of bilaterian animals. Despite their importance, the precise mechanisms by which oxygen-binding proteins influenced the early stages of multicellular evolution under varying environmental oxygen levels are not yet clear. We addressed this knowledge gap by heterologously expressing the oxygen binding proteins myoglobin and myohemerythrin in snowflake yeast, a model system of simple, undifferentiated multicellularity. These proteins increased the depth and rate of oxygen diffusion, increasing the fitness of snowflake yeast growing aerobically. Experiments show that, paradoxically, oxygen-binding proteins confer a greater fitness benefit for larger organisms under high, not low, O 2 conditions. We show via biophysical modeling that this is because facilitated diffusion is more efficient when oxygen is abundant, transporting a greater quantity of O 2 which can be used for metabolism. By alleviating anatomical diffusion limitations to oxygen consumption, the evolution of O 2 -binding proteins in the oxygen-rich Neoproterozoic may have been a key breakthrough enabling the evolution of increasingly large, complex multicellular metazoan lineages.}, } @article {pmid38103995, year = {2023}, author = {Yu, Y and Li, YP and Ren, K and Hao, X and Fru, EC and Rønn, R and Rivera, WL and Becker, K and Feng, R and Yang, J and Rensing, C}, title = {A brief history of metal recruitment in protozoan predation.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2023.11.008}, pmid = {38103995}, issn = {1878-4380}, abstract = {Metals and metalloids are used as weapons for predatory feeding by unicellular eukaryotes on prokaryotes. This review emphasizes the role of metal(loid) bioavailability over the course of Earth's history, coupled with eukaryogenesis and the evolution of the mitochondrion to trace the emergence and use of the metal(loid) prey-killing phagosome as a feeding strategy. Members of the genera Acanthamoeba and Dictyostelium use metals such as zinc (Zn) and copper (Cu), and possibly metalloids, to kill their bacterial prey after phagocytosis. We provide a potential timeline on when these capacities first evolved and how they correlate with perceived changes in metal(loid) bioavailability through Earth's history. The origin of phagotrophic eukaryotes must have postdated the Great Oxidation Event (GOE) in agreement with redox-dependent modification of metal(loid) bioavailability for phagotrophic poisoning. However, this predatory mechanism is predicted to have evolved much later - closer to the origin of the multicellular metazoans and the evolutionary development of the immune systems.}, } @article {pmid38088971, year = {2023}, author = {Miklós, M and Cseri, K and Laczkó, L and Kardos, G and Fraune, S and Tökölyi, J}, title = {Environmental bacteria increase population growth of hydra at low temperature.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1294771}, doi = {10.3389/fmicb.2023.1294771}, pmid = {38088971}, issn = {1664-302X}, abstract = {Multicellular organisms engage in complex ecological interactions with microorganisms, some of which are harmful to the host's health and fitness (e.g., pathogens or toxin-producing environmental microbiota), while others are either beneficial or have a neutral impact (as seen in components of host-associated microbiota). Although environmental microorganisms are generally considered to have no significant impact on animal fitness, there is evidence suggesting that exposure to these microbes might be required for proper immune maturation and research in vertebrates has shown that developing in a sterile environment detrimentally impacts health later in life. However, it remains uncertain whether such beneficial effects of environmental microorganisms are present in invertebrates that lack an adaptive immune system. In the present study, we conducted an experiment with field-collected Hydra oligactis, a cold-adapted freshwater cnidarian. We cultured these organisms in normal and autoclaved lake water at two distinct temperatures: 8°C and 12°C. Our findings indicated that polyps maintained in sterilized lake water displayed reduced population growth that depended on temperature, such that the effect was only present on 8°C. To better understand the dynamics of microbial communities both inhabiting polyps and their surrounding environment we conducted 16S sequencing before and after treatment, analyzing samples from both the polyps and the water. As a result of culturing in autoclaved lake water, the polyps showed a slightly altered microbiota composition, with some microbial lineages showing significant reduction in abundance, while only a few displayed increased abundances. The autoclaved lake water was recolonized, likely from the surface of hydra polyps, by a complex albeit different community of bacteria, some of which (such as Pseudomonas, Flavobacteriaceae) might be pathogenic to hydra. The abundance of the intracellular symbiont Polynucleobacter was positively related to hydra population size. These findings indicate that at low temperature environmental microbiota can enhance population growth rate in hydra, suggesting that environmental microorganisms can provide benefits to animals even in the absence of an adaptive immune system.}, } @article {pmid38076927, year = {2023}, author = {Schaible, GA and Jay, ZJ and Cliff, J and Schulz, F and Gauvin, C and Goudeau, D and Malmstrom, RR and Ruff, SE and Edgcomb, V and Hatzenpichler, R}, title = {Multicellular magnetotactic bacterial consortia are metabolically differentiated and not clonal.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.11.27.568837}, pmid = {38076927}, abstract = {UNLABELLED: Consortia of multicellular magnetotactic bacteria (MMB) are currently the only known example of bacteria without a unicellular stage in their life cycle. Because of their recalcitrance to cultivation, most previous studies of MMB have been limited to microscopic observations. To study the biology of these unique organisms in more detail, we use multiple culture-independent approaches to analyze the genomics and physiology of MMB consortia at single cell resolution. We separately sequenced the metagenomes of 22 individual MMB consortia, representing eight new species, and quantified the genetic diversity within each MMB consortium. This revealed that, counter to conventional views, cells within MMB consortia are not clonal. Single consortia metagenomes were then used to reconstruct the species-specific metabolic potential and infer the physiological capabilities of MMB. To validate genomic predictions, we performed stable isotope probing (SIP) experiments and interrogated MMB consortia using fluorescence in situ hybridization (FISH) combined with nano-scale secondary ion mass spectrometry (NanoSIMS). By coupling FISH with bioorthogonal non-canonical amino acid tagging (BONCAT) we explored their in situ activity as well as variation of protein synthesis within cells. We demonstrate that MMB consortia are mixotrophic sulfate reducers and that they exhibit metabolic differentiation between individual cells, suggesting that MMB consortia are more complex than previously thought. These findings expand our understanding of MMB diversity, ecology, genomics, and physiology, as well as offer insights into the mechanisms underpinning the multicellular nature of their unique lifestyle.

SIGNIFICANCE STATEMENT: The emergence of multicellular lifeforms represents a pivotal milestone in Earth's history, ushering in a new era of biological complexity. Because of the relative scarcity of multicellularity in the domains Bacteria and Archaea , research on the evolution of multicellularity has predominantly focused on eukaryotic model organisms. In this study, we explored the complexity of the only known bacteria without a unicellular stage in their life cycle, consortia of multicellular magnetotactic bacteria (MMB). Genomic and physiological analyses revealed that cells within individual MMB consortia are not clonal and exhibit metabolic differentiation. This implies a higher level of complexity than previously assumed for MMB consortia, prompting a reevaluation of the evolutionary factors that have led to the emergence of multicellularity. Because of their unique biology MMB consortia are ideally suited to become a model system to explore the underpinnings of bacterial multicellularity.}, } @article {pmid38066686, year = {2023}, author = {Chen, H and Shi, H and Chen, C and Jiao, Y and Wang, P and Chen, C and Li, J and Wu, LF and Song, T}, title = {Effects of static magnetic field on the sulfate metabolic pathway involved in Magnetospirillum magneticum AMB-1 cell growth and magnetosome formation.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jambio/lxad302}, pmid = {38066686}, issn = {1365-2672}, abstract = {AIMS: Magnetotactic bacteria (MTB) can use their unique intracellular magnetosome organelles to swim along the Earth's magnetic field. They play important roles in the biogeochemical cycles of iron and sulfur. Previous studies have shown that the applied magnetic fields could affect the magnetosome formation and antioxidant defense systems in MTB. However, the molecular mechanisms by which magnetic fields affect MTB cells remain unclear. We aim to better understand the interactions between magnetic fields and cells, and the mechanism of MTB adaptation to magnetic field at molecular levels.

METHODS AND RESULTS: We performed microbiological, transcriptomic and genetic experiments to analyze the effects of a weak static magnetic field (SMF) exposure on the cell growth and magnetosome formation in MTB strain Magnetospirillum magneticum AMB-1. The results showed that a 1.5 mT SMF significantly promoted the cell growth but reduced magnetosome formation in AMB-1, compared to the geomagnetic field. Transcriptomic analysis revealed decreased expressions of genes primarily involved in the sulfate reduction pathway. Consistently, knockout mutant lacking adenylyl-sulfate kinase CysC did no more react to the SMF and the differences in growth and Cmag were disappeared. Together with experimental findings of increased reactive oxidative species in the SMF-treated Wild-type strain, we proposed that cysC, as a key gene, can participate in the cells growth and mineralization in AMB-1 by SMF regulation.

CONCLUSIONS: This study suggests that the magnetic field exposure can trigger a bacterial oxidative stress response involved in AMB-1 growth and magnetosome mineralization by regulating sulfur metabolism pathway. CysC may serve as a pivotal enzyme in mediating sulfur metabolism to synchronize the impact of SMF on both growth and magnetization of AMB-1.}, } @article {pmid38060007, year = {2023}, author = {Romei, M and Carpentier, M and Chomilier, J and Lecointre, G}, title = {Origins and Functional Significance of Eukaryotic Protein Folds.}, journal = {Journal of molecular evolution}, volume = {}, number = {}, pages = {}, pmid = {38060007}, issn = {1432-1432}, support = {IPV program of Sorbonne University, PhD grant//Sorbonne Université/ ; }, abstract = {Folds are the architecture and topology of a protein domain. Categories of folds are very few compared to the astronomical number of sequences. Eukaryotes have more protein folds than Archaea and Bacteria. These folds are of two types: shared with Archaea and/or Bacteria on one hand and specific to eukaryotic clades on the other hand. The first kind of folds is inherited from the first endosymbiosis and confirms the mixed origin of eukaryotes. In a dataset of 1073 folds whose presence or absence has been evidenced among 210 species equally distributed in the three super-kingdoms, we have identified 28 eukaryotic folds unambiguously inherited from Bacteria and 40 eukaryotic folds unambiguously inherited from Archaea. Compared to previous studies, the repartition of informational function is higher than expected for folds originated from Bacteria and as high as expected for folds inherited from Archaea. The second type of folds is specifically eukaryotic and associated with an increase of new folds within eukaryotes distributed in particular clades. Reconstructed ancestral states coupled with dating of each node on the tree of life provided fold appearance rates. The rate is on average twice higher within Eukaryota than within Bacteria or Archaea. The highest rates are found in the origins of eukaryotes, holozoans, metazoans, metazoans stricto sensu, and vertebrates: the roots of these clades correspond to bursts of fold evolution. We could correlate the functions of some of the fold synapomorphies within eukaryotes with significant evolutionary events. Among them, we find evidence for the rise of multicellularity, adaptive immune system, or virus folds which could be linked to an ecological shift made by tetrapods.}, } @article {pmid38053292, year = {2023}, author = {Shelake, RM and Pramanik, D and Kim, JY}, title = {CRISPR base editor-based targeted random mutagenesis (BE-TRM) toolbox for directed evolution.}, journal = {BMB reports}, volume = {}, number = {}, pages = {}, pmid = {38053292}, issn = {1976-670X}, abstract = {Directed evolution (DE) of desired locus by targeted random mutagenesis (TRM) tools is a powerful approach for generating genetic variations with novel or improved functions, particularly in complex genomes. TRM-based DE involves developing a mutant library of targeted DNA sequences and screening the variants for the desired properties. However, DE methods have for a long time been confined to bacteria and yeasts. Lately, CRISPR/Cas and DNA deaminase-based tools that circumvent enduring barriers such as longer life cycle, small library sizes, and low mutation rates have been developed to facilitate DE in native genetic environments of multicellular organisms. Notably, deaminase-based base editing-TRM (BE-TRM) tools have greatly expanded the scope and efficiency of DE schemes by enabling base substitutions and randomization of targeted DNA sequences. BE-TRM tools provide a robust platform for the continuous molecular evolution of desired proteins, metabolic pathway engineering, creation of a mutant library of desired locus to evolve novel functions, and other applications, such as predicting mutants conferring antibiotic resistance. This review provides timely updates on the recent advances in BE-TRM tools for DE, their applications in biology, and future directions for further improvements.}, } @article {pmid38039969, year = {2023}, author = {Mulvey, H and Dolan, L}, title = {RHO of plant signaling was established early in streptophyte evolution.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2023.11.007}, pmid = {38039969}, issn = {1879-0445}, abstract = {The algal ancestors of land plants underwent a transition from a unicellular to a multicellular body plan.[1] This transition likely took place early in streptophyte evolution, sometime after the divergence of the Chlorokybophyceae/Mesostigmatophyceae lineage, but before the divergence of the Klebsormidiophyceae lineage.[2] How this transition was brought about is unknown; however, it was likely facilitated by the evolution of novel mechanisms to spatially regulate morphogenesis. In land plants, RHO of plant (ROP) signaling plays a conserved role in regulating polarized cell growth and cell division orientation to orchestrate morphogenesis.[3][,][4][,][5][,][6][,][7][,][8] ROP constitutes a plant-specific subfamily of the RHO GTPases, which are more widely conserved throughout eukaryotes.[9][,][10] Although the RHO family originated in early eukaryotes,[11][,][12] how and when the ROP subfamily originated had remained elusive. Here, we demonstrate that ROP signaling was established early in the streptophyte lineage, sometime after the divergence of the Chlorokybophyceae/Mesostigmatophyceae lineage, but before the divergence of the Klebsormidiophyceae lineage. This period corresponds to when the unicellular-to-multicellular transition likely took place in the streptophytes. In addition to being critical for the complex morphogenesis of extant land plants, we speculate that ROP signaling contributed to morphological evolution in early streptophytes.}, } @article {pmid38040554, year = {2023}, author = {Arnoux-Courseaux, M and Coudert, Y}, title = {Re-examining meristems through the lens of evo-devo.}, journal = {Trends in plant science}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tplants.2023.11.003}, pmid = {38040554}, issn = {1878-4372}, abstract = {The concept of the meristem was introduced in 1858 to characterize multicellular, formative, and proliferative tissues that give rise to the entire plant body, based on observations of vascular plants. Although its original definition did not encompass bryophytes, this concept has been used and continuously refined over the past 165 years to describe the diverse apices of all land plants. Here, we re-examine this matter in light of recent evo-devo research and show that, despite displaying high anatomical diversity, land plant meristems are unified by shared genetic control. We also propose a modular view of meristem function and highlight multiple evolutionary mechanisms that are likely to have contributed to the assembly and diversification of the varied meristems during the course of plant evolution.}, } @article {pmid38029070, year = {2023}, author = {Liu, N and Jiang, T and Cui, WP and Qi, XQ and Li, XG and Lu, Y and Wu, LF and Zhang, WJ}, title = {The TorRS two component system regulates expression of TMAO reductase in response to high hydrostatic pressure in Vibrio fluvialis.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1291578}, doi = {10.3389/fmicb.2023.1291578}, pmid = {38029070}, issn = {1664-302X}, abstract = {High hydrostatic pressure (HHP) regulated gene expression is one of the most commonly adopted strategies for microbial adaptation to the deep-sea environments. Previously we showed that the HHP-inducible trimethylamine N-oxide (TMAO) reductase improves the pressure tolerance of deep-sea strain Vibrio fluvialis QY27. Here, we investigated the molecular mechanism of HHP-responsive regulation of TMAO reductase TorA. By constructing torR and torS deletion mutants, we demonstrated that the two-component regulator TorR and sensor TorS are responsible for the HHP-responsive regulation of torA. Unlike known HHP-responsive regulatory system, the abundance of torR and torS was not affected by HHP. Complementation of the ΔtorS mutant with TorS altered at conserved phosphorylation sites revealed that the three sites were indispensable for substrate-induced regulation, but only the histidine located in the alternative transmitter domain was involved in pressure-responsive regulation. Taken together, we demonstrated that the induction of TMAO reductase by HHP is mediated through the TorRS system and proposed a bifurcation of signal transduction in pressure-responsive regulation from the substrate-induction. This work provides novel knowledge of the pressure regulated gene expression and will promote the understanding of the microbial adaptation to the deep-sea HHP environment.}, } @article {pmid38026691, year = {2023}, author = {Yoshida, K and Kato, D and Sugio, S and Takeda, I and Wake, H}, title = {Activity-dependent oligodendrocyte calcium dynamics and their changes in Alzheimer's disease.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1154196}, doi = {10.3389/fncel.2023.1154196}, pmid = {38026691}, issn = {1662-5102}, abstract = {Oligodendrocytes (OCs) form myelin around axons, which is dependent on neuronal activity. This activity-dependent myelination plays a crucial role in training and learning. Previous studies have suggested that neuronal activity regulates proliferation and differentiation of oligodendrocyte precursor cells (OPCs) and myelination. In addition, deficient activity-dependent myelination results in impaired motor learning. However, the functional response of OC responsible for neuronal activity and their pathological changes is not fully elucidated. In this research, we aimed to understand the activity-dependent OC responses and their different properties by observing OCs using in vivo two-photon microscopy. We clarified that the Ca[2+] activity in OCs is neuronal activity dependent and differentially regulated by neurotransmitters such as glutamate or adenosine triphosphate (ATP). Furthermore, in 5-month-old mice models of Alzheimer's disease, a period before the appearance of behavioral abnormalities, the elevated Ca[2+] responses in OCs are ATP dependent, suggesting that OCs receive ATP from damaged tissue. We anticipate that our research will help in determining the correct therapeutic strategy for neurodegenerative diseases beyond the synapse.}, } @article {pmid38018379, year = {2023}, author = {Digel, L and Mierzwa, M and Bonné, R and Zieger, S and Pavel, I and Ferapontova, E and Koren, K and Boesen, T and Harnisch, F and Marshall, I and Nielsen, LP and Kuhn, A}, title = {Cable Bacteria Skeletons as Catalytically Active Electrodes.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {}, number = {}, pages = {e202312647}, doi = {10.1002/anie.202312647}, pmid = {38018379}, issn = {1521-3773}, abstract = {Cable bacteria are multicellular, filamentous bacteria that use internal conductive fibers to transport electrons over centimeter distances from donors within anoxic sediment layers to oxygen at the surface. We extracted the fibers and used them as free-standing bio-based electrodes to investigate their electrocatalytic behavior. The fibers catalyzed the reversible interconversion of oxygen and water, and an electric current was running through the fibers even when the potential difference was generated solely by a gradient of oxygen concentration. Oxygen reduction as well as oxygen evolution were confirmed by optical measurements. Within living cable bacteria, oxygen reduction by direct electrocatalysis on the fibers and not by membrane-bound proteins readily explains exceptionally high cell-specific oxygen consumption rates observed in the oxic zone, while electrocatalytic water oxidation may provide oxygen to cells in the anoxic zone.}, } @article {pmid38015755, year = {2023}, author = {Zhang, Y and Fu, M and Wang, H and Sun, H}, title = {Advances in the Construction and Application of Thyroid Organoids.}, journal = {Physiological research}, volume = {72}, number = {5}, pages = {557-564}, pmid = {38015755}, issn = {1802-9973}, abstract = {Organoids are complex multicellular structures that stem cells self-organize in three-dimensional (3D) cultures into anatomical structures and functional units similar to those seen in the organs from which they originate. This review describes the construction of thyroid organoids and the research progress that has occurred in models of thyroid-related disease. As a novel tool for modeling in a 3D multicellular environment, organoids help provide some useful references for the study of the pathogenesis of thyroid disease.}, } @article {pmid38014282, year = {2023}, author = {Bingham, EP and Ratcliff, WC}, title = {A non-adaptive explanation for macroevolutionary patterns in the evolution of complex multicellularity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.11.11.566713}, pmid = {38014282}, abstract = {"Complex multicellularity", conventionally defined as large organisms with many specialized cell types, has evolved five times independently in eukaryotes, but never within prokaryotes. A number hypotheses have been proposed to explain this phenomenon, most of which posit that eukaryotes evolved key traits (e . g ., dynamic cytoskeletons, alternative mechanisms of gene regulation, or subcellular compartments) which were a necessary prerequisite for the evolution of complex multicellularity. Here we propose an alternative, non-adaptive hypothesis for this broad macroevolutionary pattern. By binning cells into groups with finite genetic bottlenecks between generations, the evolution of multicellularity greatly reduces the effective population size (Ne) of cellular populations, increasing the role of genetic drift in evolutionary change. While both prokaryotes and eukaryotes experience this phenomenon, they have opposite responses to drift: mutational biases in eukaryotes tend to drive genomic expansion, providing additional raw genetic material for subsequent multicellular innovation, while prokaryotes generally face genomic erosion. These effects become more severe as organisms evolve larger size and more stringent genetic bottlenecks between generations- both of which are hallmarks of complex multicellularity. Taken together, we hypothesize that it is these idiosyncratic lineagespecific mutational biases, rather than cell-biological innovations within eukaryotes, that underpins the long-term divergent evolution of complex multicellularity across the tree of life.}, } @article {pmid37978256, year = {2023}, author = {Ongenae, V and Kempff, A and van Neer, V and Shomar, H and Tesson, F and Rozen, D and Briegel, A and Claessen, D}, title = {Genome sequence and characterization of Streptomyces phages Vanseggelen and Verabelle, representing two new species within the genus Camvirus.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20153}, pmid = {37978256}, issn = {2045-2322}, support = {VI.C.192.002//NWO Vici/ ; }, mesh = {*Bacteriophages ; *Streptomyces/genetics ; Genome, Viral ; DNA, Viral/genetics ; *Siphoviridae/genetics ; Phylogeny ; }, abstract = {Despite the rising interest in bacteriophages, little is known about their infection cycle and lifestyle in a multicellular host. Even in the model system Streptomyces, only a small number of phages have been sequenced and well characterized so far. Here, we report the complete characterization and genome sequences of Streptomyces phages Vanseggelen and Verabelle isolated using Streptomyces coelicolor as a host. A wide range of Streptomyces strains could be infected by both phages, but neither of the two phages was able to infect members of the closely related sister genus Kitasatospora. The phages Vanseggelen and Verabelle have a double-stranded DNA genome with lengths of 48,720 and 48,126 bp, respectively. Both phage genomes contain 72 putative genes, and the presence of an integrase encoding protein indicates a lysogenic lifestyle. Characterization of the phages revealed their stability over a wide range of temperatures (30-45 °C) and pH values (4-10). In conclusion, Streptomyces phage Vanseggelen and Streptomyces phage Verabelle are newly isolated phages that can be classified as new species in the genus Camvirus, within the subfamily Arquattrovirinae.}, } @article {pmid37552891, year = {2023}, author = {Goehring, L and Huang, TT and Smith, DJ}, title = {Transcription-Replication Conflicts as a Source of Genome Instability.}, journal = {Annual review of genetics}, volume = {57}, number = {}, pages = {157-179}, doi = {10.1146/annurev-genet-080320-031523}, pmid = {37552891}, issn = {1545-2948}, support = {R01 ES031658/ES/NIEHS NIH HHS/United States ; R35 GM139610/GM/NIGMS NIH HHS/United States ; }, abstract = {Transcription and replication both require large macromolecular complexes to act on a DNA template, yet these machineries cannot simultaneously act on the same DNA sequence. Conflicts between the replication and transcription machineries (transcription-replication conflicts, or TRCs) are widespread in both prokaryotes and eukaryotes and have the capacity to both cause DNA damage and compromise complete, faithful replication of the genome. This review will highlight recent studies investigating the genomic locations of TRCs and the mechanisms by which they may be prevented, mitigated, or resolved. We address work from both model organisms and mammalian systems but predominantly focus on multicellular eukaryotes owing to the additional complexities inherent in the coordination of replication and transcription in the context of cell type-specific gene expression and higher-order chromatin organization.}, } @article {pmid38003023, year = {2023}, author = {Toch, K and Buczek, M and Labocha, MK}, title = {Genetic Interactions in Various Environmental Conditions in Caenorhabditis elegans.}, journal = {Genes}, volume = {14}, number = {11}, pages = {}, doi = {10.3390/genes14112080}, pmid = {38003023}, issn = {2073-4425}, support = {2015/17/B/NZ8/02366//National Science Center/ ; }, abstract = {Although it is well known that epistasis plays an important role in many evolutionary processes (e.g., speciation, evolution of sex), our knowledge on the frequency and prevalent sign of epistatic interactions is mainly limited to unicellular organisms or cell cultures of multicellular organisms. This is even more pronounced in regard to how the environment can influence genetic interactions. To broaden our knowledge in that respect we studied gene-gene interactions in a whole multicellular organism, Caenorhabditis elegans. We screened over one thousand gene interactions, each one in standard laboratory conditions, and under three different stressors: heat shock, oxidative stress, and genotoxic stress. Depending on the condition, between 7% and 22% of gene pairs showed significant genetic interactions and an overall sign of epistasis changed depending on the condition. Sign epistasis was quite common, but reciprocal sign epistasis was extremally rare. One interaction was common to all conditions, whereas 78% of interactions were specific to only one environment. Although epistatic interactions are quite common, their impact on evolutionary processes will strongly depend on environmental factors.}, } @article {pmid37996670, year = {2024}, author = {Spradling, AC}, title = {The Ancient Origin and Function of Germline Cysts.}, journal = {Results and problems in cell differentiation}, volume = {71}, number = {}, pages = {3-21}, pmid = {37996670}, issn = {0080-1844}, abstract = {Gamete production in most animal species is initiated within an evolutionarily ancient multicellular germline structure, the germline cyst, whose interconnected premeiotic cells synchronously develop from a single progenitor arising just downstream from a stem cell. Cysts in mice, Drosophila, and many other animals protect developing sperm, while in females, cysts generate nurse cells that guard sister oocytes from transposons (TEs) and help them grow and build a Balbiani body. However, the origin and extreme evolutionary conservation of germline cysts remains a mystery. We suggest that cysts arose in ancestral animals like Hydra and Planaria whose multipotent somatic and germline stem cells (neoblasts) express genes conserved in all animal germ cells and frequently begin differentiation in cysts. A syncytial state is proposed to help multipotent stem cell chromatin transition to an epigenetic state with heterochromatic domains suitable for TE repression and specialized function. Most modern animals now lack neoblasts but have retained stem cells and cysts in their early germlines, which continue to function using this ancient epigenetic strategy.}, } @article {pmid37990147, year = {2023}, author = {Jin, H and Zhang, W and Liu, H and Bao, Y}, title = {Genome-wide identification and characteristic analysis of ETS gene family in blood clam Tegillarca granosa.}, journal = {BMC genomics}, volume = {24}, number = {1}, pages = {700}, pmid = {37990147}, issn = {1471-2164}, support = {LZ20C190001//Key Natural Science Foundation of Zhejiang/ ; 32273123//National Science Foundation of China/ ; 2021C02069-7//Zhejiang Major Program of Science and Technology/ ; LQ23C190007//Science Foundation of Zhejiang/ ; 2021S014//Ningbo Public Benefit Research Key Project/ ; }, mesh = {Humans ; Animals ; Phylogeny ; *Arcidae/genetics/metabolism ; Proto-Oncogene Proteins c-ets/genetics/metabolism ; Genome ; *Bivalvia/genetics ; }, abstract = {BACKGROUND: ETS transcription factors, known as the E26 transformation-specific factors, assume a critical role in the regulation of various vital biological processes in animals, including cell differentiation, the cell cycle, and cell apoptosis. However, their characterization in mollusks is currently lacking.

RESULTS: The current study focused on a comprehensive analysis of the ETS genes in blood clam Tegillarca granosa and other mollusk genomes. Our phylogenetic analysis revealed the absence of the SPI and ETV subfamilies in mollusks compared to humans. Additionally, several ETS genes in mollusks were found to lack the PNT domain, potentially resulting in a diminished ability of ETS proteins to bind target genes. Interestingly, the bivalve ETS1 genes exhibited significantly high expression levels during the multicellular proliferation stage and in gill tissues. Furthermore, qRT-PCR results showed that Tg-ETS-14 (ETS1) is upregulated in the high total hemocyte counts (THC) population of T. granosa, suggesting it plays a significant role in stimulating hemocyte proliferation.

CONCLUSION: Our study significantly contributes to the comprehension of the evolutionary aspects concerning the ETS gene family, while also providing valuable insights into its role in fostering hemocyte proliferation across mollusks.}, } @article {pmid37993452, year = {2023}, author = {Nicolas, E and Simion, P and Guérineau, M and Terwagne, M and Colinet, M and Virgo, J and Lingurski, M and Boutsen, A and Dieu, M and Hallet, B and Van Doninck, K}, title = {Horizontal acquisition of a DNA ligase improves DNA damage tolerance in eukaryotes.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {7638}, pmid = {37993452}, issn = {2041-1723}, abstract = {Bdelloid rotifers are part of the restricted circle of multicellular animals that can withstand a wide range of genotoxic stresses at any stage of their life cycle. In this study, bdelloid rotifer Adineta vaga is used as a model to decipher the molecular basis of their extreme tolerance. Proteomic analysis shows that a specific DNA ligase, different from those usually involved in DNA repair in eukaryotes, is strongly over-represented upon ionizing radiation. A phylogenetic analysis reveals its orthology to prokaryotic DNA ligase E, and its horizontal acquisition by bdelloid rotifers and plausibly other eukaryotes. The fungus Mortierella verticillata, having a single copy of this DNA Ligase E homolog, also exhibits an increased radiation tolerance with an over-expression of this DNA ligase E following X-ray exposure. We also provide evidence that A. vaga ligase E is a major contributor of DNA breaks ligation activity, which is a common step of all important DNA repair pathways. Consistently, its heterologous expression in human cell lines significantly improves their radio-tolerance. Overall, this study highlights the potential of horizontal gene transfers in eukaryotes, and their contribution to the adaptation to extreme conditions.}, } @article {pmid37981028, year = {2023}, author = {Rossi, SA and García-Barbazán, I and Chamorro-Herrero, I and Taborda, CP and Zaragoza, Ó and Zambrano, A}, title = {Use of 2D Minilungs from Human Embryonic Stem Cells to Study the Interaction of Cryptococcus neoformans with the Respiratory Tract.}, journal = {Microbes and infection}, volume = {}, number = {}, pages = {105260}, doi = {10.1016/j.micinf.2023.105260}, pmid = {37981028}, issn = {1769-714X}, abstract = {Organoids can meet the needs between the use of cell culture and in vivo work, bringing together aspects of multicellular tissues, providing a more similar in vitro system for the study of various components, including host-interactions with pathogens and drug response. Organoids are structures that resemble organs in vivo, originating from pluripotent stem cells (PSCs) or adult stem cells (ASCs). There is great interest in deepening the understanding of the use of this technology to produce information about fungal infections and their treatments. This work aims the use 2D human lung organoid derived from human embryonic stem cells (hESCs), to investigate Cryptococcus neoformans-host interactions. C. neoformans is an opportunistic fungus acquired by inhalation that causes systemic mycosis mainly in immunocompromised individuals. Our work highlights the suitability of human minilungs for the study of C. neoformans infection (adhesion, invasion and replication), the interaction with the surfactant and induction of the host's alveolar pro-inflammatory response.}, } @article {pmid37971931, year = {2023}, author = {Zou, Y and Sabljić, I and Horbach, N and Dauphinee, AN and Åsman, A and Sancho Temino, L and Minina, EA and Drag, M and Stael, S and Poreba, M and Ståhlberg, J and Bozhkov, PV}, title = {Thermoprotection by a cell membrane-localized metacaspase in a green alga.}, journal = {The Plant cell}, volume = {}, number = {}, pages = {}, doi = {10.1093/plcell/koad289}, pmid = {37971931}, issn = {1532-298X}, abstract = {Caspases are restricted to animals, while other organisms, including plants possess metacaspases (MCAs), a more ancient and broader class of structurally related yet biochemically distinct proteases. Our current understanding of plant MCAs is derived from studies in streptophytes, and mostly in Arabidopsis (Arabidopsis thaliana) with nine MCAs with partially redundant activities. In contrast to streptophytes, most chlorophytes contain only one or two uncharacterized MCAs, providing an excellent platform for MCA research. Here we investigated CrMCA-II, the single type-II MCA from the model chlorophyte Chlamydomonas (Chlamydomonas reinhardtii). Surprisingly, unlike other studied MCAs and similar to caspases, CrMCA-II dimerizes both in vitro and in vivo. Furthermore, activation of CrMCA-II in vivo correlated with its dimerization. Most of CrMCA-II in the cell was present as a proenzyme (zymogen) attached to the plasma membrane (PM). Deletion of CrMCA-II by genome editing compromised thermotolerance, leading to increased cell death under heat stress. Adding back either wild-type or a catalytically dead CrMCA-II restored thermoprotection, suggesting that its proteolytic activity is dispensable for this effect. Finally, we connected the non-proteolytic role of CrMCA-II in thermotolerance to the ability to modulate PM fluidity. Our study reveals an ancient, MCA-dependent thermotolerance mechanism retained by Chlamydomonas and probably lost during the evolution of multicellularity.}, } @article {pmid37963956, year = {2023}, author = {Tissot, S and Guimard, L and Meliani, J and Boutry, J and Dujon, AM and Capp, JP and Tökölyi, J and Biro, PA and Beckmann, C and Fontenille, L and Do Khoa, N and Hamede, R and Roche, B and Ujvari, B and Nedelcu, AM and Thomas, F}, title = {The impact of food availability on tumorigenesis is evolutionarily conserved.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {19825}, pmid = {37963956}, issn = {2045-2322}, abstract = {The inability to control cell proliferation results in the formation of tumors in many multicellular lineages. Nonetheless, little is known about the extent of conservation of the biological traits and ecological factors that promote or inhibit tumorigenesis across the metazoan tree. Particularly, changes in food availability have been linked to increased cancer incidence in humans, as an outcome of evolutionary mismatch. Here, we apply evolutionary oncology principles to test whether food availability, regardless of the multicellular lineage considered, has an impact on tumorigenesis. We used two phylogenetically unrelated model systems, the cnidarian Hydra oligactis and the fish Danio rerio, to investigate the impact of resource availability on tumor occurrence and progression. Individuals from healthy and tumor-prone lines were placed on four diets that differed in feeding frequency and quantity. For both models, frequent overfeeding favored tumor emergence, while lean diets appeared more protective. In terms of tumor progression, high food availability promoted it, whereas low resources controlled it, but without having a curative effect. We discuss our results in light of current ideas about the possible conservation of basic processes governing cancer in metazoans (including ancestral life history trade-offs at the cell level) and in the framework of evolutionary medicine.}, } @article {pmid37961564, year = {2023}, author = {Mukherjee, A and Huang, Y and Elgeti, J and Oh, S and Neliat, AR and Schüttler, J and Benites, NC and Liu, X and Barboiu, M and Stocker, H and Kirschner, MW and Basan, M}, title = {Membrane potential mediates an ancient mechano-transduction mechanism for multi-cellular homeostasis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.11.02.565386}, pmid = {37961564}, abstract = {Membrane potential is a property of all living cells [1] . However, its physiological role in nonexcitable cells is poorly understood. Resting membrane potential is typically considered fixed for a given cell type and under tight homeostatic control [2] , akin to body temperature in mammals. Contrary to this widely accepted paradigm, we found that membrane potential is a dynamic property that directly reflects tissue density and mechanical forces acting on the cell. Serving as a quasi-instantaneous, global readout of density and mechanical pressure, membrane potential is integrated with signal transduction networks by affecting the conformation and clustering of proteins in the membrane [3,4] , as well as the transmembrane flux of key signaling ions [5,6] . Indeed, we show that important mechano-sensing pathways, YAP, Jnk and p38 [7-121314] , are directly controlled by membrane potential. We further show that mechano-transduction via membrane potential plays a critical role in the homeostasis of epithelial tissues, setting tissue density by controlling proliferation and cell extrusion of cells. Moreover, a wave of depolarization triggered by mechanical stretch enhances the speed of wound healing. Mechano-transduction via membrane potential likely constitutes an ancient homeostatic mechanism in multi-cellular organisms, potentially serving as a steppingstone for the evolution of excitable tissues and neuronal mechano-sensing. The breakdown of membrane potential mediated homeostatic regulation may contribute to tumor growth.}, } @article {pmid37317487, year = {2023}, author = {Fulda, FC}, title = {Agential autonomy and biological individuality.}, journal = {Evolution & development}, volume = {25}, number = {6}, pages = {353-370}, doi = {10.1111/ede.12450}, pmid = {37317487}, issn = {1525-142X}, mesh = {Humans ; Animals ; *Biological Evolution ; *Symbiosis ; }, abstract = {What is a biological individual? How are biological individuals individuated? How can we tell how many individuals there are in a given assemblage of biological entities? The individuation and differentiation of biological individuals are central to the scientific understanding of living beings. I propose a novel criterion of biological individuality according to which biological individuals are autonomous agents. First, I articulate an ecological-dynamical account of natural agency according to which, agency is the gross dynamical capacity of a goal-directed system to bias its repertoire to respond to its conditions as affordances. Then, I argue that agents or agential dynamical systems can be agentially dependent on, or agentially autonomous from, other agents and that this agential dependence/autonomy can be symmetrical or asymmetrical, strong or weak. Biological individuals, I propose, are all and only those agential dynamical systems that are strongly agentially autonomous. So, to determine how many individuals there are in a given multiagent aggregate, such as multicellular organism, a colony, symbiosis, or a swarm, we first have to identify how many agential dynamical systems there are, and then what their relations of agential dependence/autonomy are. I argue that this criterion is adequate to the extent that it vindicates the paradigmatic cases, and explains why the paradigmatic cases are paradigmatic, and why the problematic cases are problematic. Finally, I argue for the importance of distinguishing between agential and causal dependence and show the relevance of agential autonomy for understanding the explanatory structure of evolutionary developmental biology.}, } @article {pmid37953852, year = {2023}, author = {Gavrilov-Zimin, IA}, title = {Ancient reproductive modes and criteria of multicellularity.}, journal = {Comparative cytogenetics}, volume = {17}, number = {}, pages = {195-238}, pmid = {37953852}, issn = {1993-0771}, abstract = {It is demonstrated that the initial method of fertilization in animals (Metazoa), embryophyte plants (Embryophyta), most groups of multicellular oogamous algae, oogamous and pseudoogamous multicellular fungi was internal fertilization (in the broad meaning) in/on the body of a maternal organism. Accordingly, during the bisexual process, the initial method of formation of a daughter multicellular organism in animals was viviparity, and in embryophyte plants and most groups of oogamous multicellular algae - the germination of a zygote in/on the body of maternal organism. The reproductive criteria of multicellularity are proposed and discussed. In this regard, the multicellularity is considered to subdivide terminologically into three variants: 1) protonemal, the most simple, characteristic of multicellular prokaryotes, most groups of multicellular algae and gametophytes of some higher plants; 2) siphonoseptal, found among multicellular fungi, some groups of green and yellow-green algae; 3) embryogenic, most complicated, known in all animals (Metazoa), all sporophytes and some gametophytes of higher plants (Embryophyta), charophyte green algae Charophyceae s.s., oogamous species of green and brown algae, some genera of red algae. In addition to the well-known division of reproduction methods into sexual and asexual, it is proposed to divide the reproduction of multicellular organisms into monocytic (the emergence of a new organism from one cell sexually or asexually) and polycytic (fragmentation, longitudinal / transverse division or budding based on many cells of the body of the mother organism), since these two ways have different evolutionary and ontogenetic origins.}, } @article {pmid37949064, year = {2023}, author = {Liu, D and Vargas-García, CA and Singh, A and Umen, J}, title = {A cell-based model for size control in the multiple fission alga Chlamydomonas reinhardtii.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2023.10.023}, pmid = {37949064}, issn = {1879-0445}, abstract = {Understanding how population-size homeostasis emerges from stochastic individual cell behaviors remains a challenge in biology.[1][,][2][,][3][,][4][,][5][,][6][,][7] The unicellular green alga Chlamydomonas reinhardtii (Chlamydomonas) proliferates using a multiple fission cell cycle, where a prolonged G1 phase is followed by n rounds of alternating division cycles (S/M) to produce 2[n] daughters. A "Commitment" sizer in mid-G1 phase ensures sufficient cell growth before completing the cell cycle. A mitotic sizer couples mother-cell size to division number (n) such that daughter size distributions are uniform regardless of mother size distributions. Although daughter size distributions were highly robust to altered growth conditions, ∼40% of daughter cells fell outside of the 2-fold range expected from a "perfect" multiple fission sizer.[7][,][8] A simple intuitive power law model with stochastic noise failed to reproduce individual division behaviors of tracked single cells. Through additional iterative modeling, we identified an alternative modified threshold (MT) model, where cells need to cross a threshold greater than 2-fold their median starting size to become division-competent (i.e., Committed), after which their behaviors followed a power law model. The Commitment versus mitotic size threshold uncoupling in the MT model was likely a key pre-adaptation in the evolution of volvocine algal multicellularity. A similar experimental approach was used in size mutants mat3/rbr and dp1 that are, respectively, missing repressor or activator subunits of the retinoblastoma tumor suppressor complex (RBC). Both mutants showed altered relationships between Commitment and mitotic sizer, suggesting that RBC functions to decouple the two sizers.}, } @article {pmid37947621, year = {2023}, author = {Wang, X and Xu, X and Wang, Z}, title = {The Post-Translational Role of UFMylation in Physiology and Disease.}, journal = {Cells}, volume = {12}, number = {21}, pages = {}, doi = {10.3390/cells12212543}, pmid = {37947621}, issn = {2073-4409}, support = {32090031, 32000911//NSFC/ ; }, abstract = {Ubiquitin-fold modifier 1 (UFM1) is a newly identified ubiquitin-like protein that has been conserved during the evolution of multicellular organisms. In a similar manner to ubiquitin, UFM1 can become covalently linked to the lysine residue of a substrate via a dedicated enzymatic cascade. Although a limited number of substrates have been identified so far, UFM1 modification (UFMylation) has been demonstrated to play a vital role in a variety of cellular activities, including mammalian development, ribosome biogenesis, the DNA damage response, endoplasmic reticulum stress responses, immune responses, and tumorigenesis. In this review, we summarize what is known about the UFM1 enzymatic cascade and its biological functions, and discuss its recently identified substrates. We also explore the pathological role of UFMylation in human disease and the corresponding potential therapeutic targets and strategies.}, } @article {pmid37745323, year = {2023}, author = {Johnson, JAI and Stein-O'Brien, GL and Booth, M and Heiland, R and Kurtoglu, F and Bergman, D and Bucher, E and Deshpande, A and Forjaz, A and Getz, M and Godet, I and Lyman, M and Metzcar, J and Mitchell, J and Raddatz, A and Rocha, HL and Solorzano, J and Sundus, A and Wang, Y and Gilkes, DM and Kagohara, LT and Kiemen, AL and Thompson, ED and Wirtz, D and Wu, PH and Zaidi, N and Zheng, L and Zimmerman, JW and Jaffee, EM and Chang, YH and Coussens, L and Gray, J and Heiser, LM and Fertig, EJ and Macklin, P}, title = {Digitize your Biology! Modeling multicellular systems through interpretable cell behavior.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.09.17.557982}, pmid = {37745323}, support = {R00 NS122085/NS/NINDS NIH HHS/United States ; 75N91019D00024/CA/NCI NIH HHS/United States ; P50 CA062924/CA/NCI NIH HHS/United States ; K08 CA248624/CA/NCI NIH HHS/United States ; P01 CA247886/CA/NCI NIH HHS/United States ; U54 CA268083/CA/NCI NIH HHS/United States ; U54 CA274371/CA/NCI NIH HHS/United States ; U01 CA253403/CA/NCI NIH HHS/United States ; U01 CA212007/CA/NCI NIH HHS/United States ; U01 CA232137/CA/NCI NIH HHS/United States ; }, abstract = {Cells are fundamental units of life, constantly interacting and evolving as dynamical systems. While recent spatial multi-omics can quantitate individual cells' characteristics and regulatory programs, forecasting their evolution ultimately requires mathematical modeling. We develop a conceptual framework--a cell behavior hypothesis grammar--that uses natural language statements (cell rules) to create mathematical models. This allows us to systematically integrate biological knowledge and multi-omics data to make them computable. We can then perform virtual "thought experiments" that challenge and extend our understanding of multicellular systems, and ultimately generate new testable hypotheses. In this paper, we motivate and describe the grammar, provide a reference implementation, and demonstrate its potential through a series of examples in tumor biology and immunotherapy. Altogether, this approach provides a bridge between biological, clinical, and systems biology researchers for mathematical modeling of biological systems at scale, allowing the community to extrapolate from single-cell characterization to emergent multicellular behavior.}, } @article {pmid37475165, year = {2023}, author = {Lamża, Ł}, title = {Diversity of 'simple' multicellular eukaryotes: 45 independent cases and six types of multicellularity.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {98}, number = {6}, pages = {2188-2209}, doi = {10.1111/brv.13001}, pmid = {37475165}, issn = {1469-185X}, mesh = {Phylogeny ; *Eukaryota/genetics ; *Fungi ; Biological Evolution ; }, abstract = {Multicellularity evolved multiple times in the history of life, with most reviewers agreeing that it appeared at least 20 times in eukaryotes. However, a specific list of multicellular eukaryotes with clear criteria for inclusion has not yet been published. Herein, an updated critical review of eukaryotic multicellularity is presented, based on current understanding of eukaryotic phylogeny and new discoveries in microbiology, phycology and mycology. As a result, 45 independent multicellular lineages are identified that fall into six distinct types. Functional criteria, as distinct from a purely topological definition of a cell, are introduced to bring uniformity and clarity to the existing definitions of terms such as colony, multicellularity, thallus or plasmodium. The category of clonal multicellularity is expanded to include: (i) septated multinucleated thalli found in Pseudofungi and early-branching Fungi such as Chytridiomycota and Blastocladiomycota; and (ii) multicellular reproductive structures formed by plasmotomy in intracellular parasites such as Phytomyxea. Furthermore, (iii) endogeneous budding, as found in Paramyxida, is described as a form of multicellularity. The best-known case of clonal multicellularity, i.e. (iv) non-separation of cells after cell division, as known from Metazoa and Ochrophyta, is also discussed. The category of aggregative multicellularity is expanded to include not only (v) pseudoplasmodial forms, such a sorocarp-forming Acrasida, but also (vi) meroplasmodial organisms, such as members of Variosea or Filoreta. A common set of topological, geometric, genetic and life-cycle criteria are presented that form a coherent, philosophically sound framework for discussing multicellularity. A possibility of a seventh type of multicellularity is discussed, that of multi-species superorganisms formed by protists with obligatory bacterial symbionts, such as some members of Oxymonada or Parabasalia. Its inclusion is dependent on the philosophical stance taken towards the concepts of individuality and organism in biology. Taxa that merit special attention are identified, such as colonial Centrohelea, and a new speculative form of multicellularity, possibly present in some reticulopodial amoebae, is briefly described. Because of insufficient phylogenetic and morphological data, not all lineages could be unequivocally identified, and the true total number of all multicellular eukaryotic lineages is therefore higher, likely close to a hundred.}, } @article {pmid37931037, year = {2023}, author = {Dupouy, G and Cashell, R and Brychkova, G and Tuteja, R and McKeown, PC and Spillane, C}, title = {PICKLE RELATED 2 is a Neofunctionalized Gene Duplicate Under Positive Selection With Antagonistic Effects to the Ancestral PICKLE Gene on the Seed Transcriptome.}, journal = {Genome biology and evolution}, volume = {15}, number = {11}, pages = {}, doi = {10.1093/gbe/evad191}, pmid = {37931037}, issn = {1759-6653}, abstract = {The evolution and diversification of proteins capable of remodeling domains has been critical for transcriptional reprogramming during cell fate determination in multicellular eukaryotes. Chromatin remodeling proteins of the CHD3 family have been shown to have important and antagonistic impacts on seed development in the model plant, Arabidopsis thaliana, yet the basis of this functional divergence remains unknown. In this study, we demonstrate that genes encoding the CHD3 proteins PICKLE (PKL) and PICKLE-RELATED 2 (PKR2) originated from a duplication event during the diversification of crown Brassicaceae, and that these homologs have undergone distinct evolutionary trajectories since this duplication, with PKR2 fast evolving under positive selection, while PKL is subject to purifying selection. We find that the rapid evolution of PKR2 under positive selection reduces the encoded protein's intrinsic disorder, possibly suggesting a tertiary structure configuration which differs from that of PKL. Our whole genome transcriptome analysis in seeds of pkr2 and pkl mutants reveals that they act antagonistically on the expression of specific sets of genes, providing a basis for their differing roles in seed development. Our results provide insights into how gene duplication and neofunctionalization can lead to differing and antagonistic selective pressures on transcriptomes during plant reproduction, as well as on the evolutionary diversification of the CHD3 family within seed plants.}, } @article {pmid37925718, year = {2023}, author = {Fung, L and Konkol, A and Ishikawa, T and Larson, BT and Brunet, T and Goldstein, RE}, title = {Swimming, Feeding, and Inversion of Multicellular Choanoflagellate Sheets.}, journal = {Physical review letters}, volume = {131}, number = {16}, pages = {168401}, doi = {10.1103/PhysRevLett.131.168401}, pmid = {37925718}, issn = {1079-7114}, abstract = {The recent discovery of the striking sheetlike multicellular choanoflagellate species Choanoeca flexa that dynamically interconverts between two hemispherical forms of opposite orientation raises fundamental questions in cell and evolutionary biology, as choanoflagellates are the closest living relatives of animals. It similarly motivates questions in fluid and solid mechanics concerning the differential swimming speeds in the two states and the mechanism of curvature inversion triggered by changes in the geometry of microvilli emanating from each cell. Here we develop fluid dynamical and mechanical models to address these observations and show that they capture the main features of the swimming, feeding, and inversion of C. flexa colonies, which can be viewed as active, shape-shifting polymerized membranes.}, } @article {pmid37921840, year = {2023}, author = {Dai, J and Li, XG and Zhang, WJ and Wu, LF}, title = {Tepidibacter hydrothermalis sp. nov., a novel anaerobic bacterium isolated from a deep-sea hydrothermal vent.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {73}, number = {11}, pages = {}, doi = {10.1099/ijsem.0.006151}, pmid = {37921840}, issn = {1466-5034}, abstract = {A novel anaerobic heterotrophic bacterium, designated strain SWIR-1[T], was isolated from a deep-sea hydrothermal vent field sample collected from the Southwest Indian Ridge at a depth of 2700 m. Phylogenetic analysis indicated that strain SWIR-1[T] belongs to the genus Tepidibacter, and the most closely related species are Tepidibacter mesophilus B1[T] (99.1 % 16S rRNA gene sequence similarity), Tepidibacter formicigenes DV1184[T] (94.6 %) and Tepidibacter thalassicus SC562[T] (93.9 %). Strain SWIR-1[T] shares 77.3-87.2 % average nucleotide identity and 21.5-35.7 % digital DNA-DNA hybridization values with the three type strains of Tepidibacter species. Cells of strain SWIR-1[T] were Gram-stain-positive, motile, short straight rods. Endospores were observed in stationary-phase cells when grown on Thermococcales rich medium. Strain SWIR-1[T] grew at 15-45 °C (optimum, 30°C), at pH 5.5-8.0 (optimum, pH 7.0) and with 1.0-6.0 % (w/v) NaCl (optimum, 2.0 %). Substrates utilized by strain SWIR-1[T] included complex proteinaceous, chitin, starch, lactose, maltose, fructose, galactose, glucose, rhamnose, arabinose, ribose, alanine, glycine and glycerol. The major fermentation products from glucose were acetate, lactate, H2 and CO2. Elemental sulphur, sulphate, thiosulphate, sulphite, fumarate, nitrate, nitrite and FeCl3 are not used as terminal electron acceptors. The main cellular fatty acids consisted of iso-C15 : 0 (28.4 %), C15 : 1 iso F (15.4 %) and C16 : 0 (9.8 %). The major polar lipids were phospholipids and glycolipids. No respiratory quinones were detected. Genomic comparison revealed a distinctive blended gene cluster comprising hyb-tat-hyp genes, which play a crucial role in the synthesis, maturation, activation and export of NiFe-hydrogenase. Based on the phylogenetic analysis, genomic, physiologic and chemotaxonomic characteristics, strain SWIR-1[T] is considered to represent a novel species within the genus Tepidibacter, for which the name Tepidibacter hydrothermalis sp. nov. is proposed. The type strain is strain SWIR-1[T] (=DSM 113848[T]=MCCC 1K07078[T]).}, } @article {pmid37916911, year = {2023}, author = {Ekdahl, LI and Salcedo, JA and Dungan, MM and Mason, DV and Myagmarsuren, D and Murphy, HA}, title = {Selection on plastic adherence leads to hyper-multicellular strains and incidental virulence in the budding yeast.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, doi = {10.7554/eLife.81056}, pmid = {37916911}, issn = {2050-084X}, support = {R15-GM122032/NH/NIH HHS/United States ; }, abstract = {Many disease-causing microbes are not obligate pathogens; rather, they are environmental microbes taking advantage of an ecological opportunity. The existence of microbes whose life cycle does not require a host and are not normally pathogenic, yet are well-suited to host exploitation, is an evolutionary puzzle. One hypothesis posits that selection in the environment may favor traits that incidentally lead to pathogenicity and virulence, or serve as pre-adaptations for survival in a host. An example of such a trait is surface adherence. To experimentally test the idea of 'accidental virulence', replicate populations of Saccharomyces cerevisiae were evolved to attach to a plastic bead for hundreds of generations. Along with plastic adherence, two multicellular phenotypes- biofilm formation and flor formation- increased; another phenotype, pseudohyphal growth, responded to the nutrient limitation. Thus, experimental selection led to the evolution of highly-adherent, hyper-multicellular strains. Wax moth larvae injected with evolved hyper-multicellular strains were significantly more likely to die than those injected with evolved non-multicellular strains. Hence, selection on plastic adherence incidentally led to the evolution of enhanced multicellularity and increased virulence. Our results support the idea that selection for a trait beneficial in the open environment can inadvertently generate opportunistic, 'accidental' pathogens.}, } @article {pmid37905027, year = {2023}, author = {Page-McCaw, PS and Pokidysheva, EN and Darris, CE and Chetyrkin, S and Fidler, AL and Murawala, P and Gallup, J and , and Hudson, JK and Hudson, BG}, title = {Collagen IV of basement membranes: I. Origin and diversification of COL4 genes enabling animal evolution.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.10.18.563013}, pmid = {37905027}, abstract = {Collagen IV is a primordial component of basement membranes, a specialized form of extracellular matrix that enabled multi-cellular epithelial tissues. In mammals, collagen IV assembles from a family of six α-chains (α1 to α6), encoded by six genes (COL4A1 to COL4A6), into three distinct scaffolds: the α121, the α345 and a mixed scaffold containing both α121 and α565. The six mammalian COL4A genes occur in pairs that occur in a head-to-head arrangement on three distinct chromosomes. In Alport syndrome, variants in the COL4A3, 4 or 5 genes cause either loss or defective assembly of the collagen IV [α345] scaffold which results in a dysfunctional glomerular basement membrane, proteinuria and progression to renal failure in millions of people worldwide. Here, we determine the evolutionary emergence and diversification of the COL4A genes using comparative genomics and biochemical analyses. Using syntenic relationships to genes closely linked to the COL4A genes, we determine that the COL4A3 and COL4A4 gene pair appeared in cyclostomes (hagfish and lampreys) while the COL4A5 and COL4A6 gene pair emerged in gnathostomes, jawed vertebrates. The more basal chordate species, lancelets and tunicates, do not have discrete kidneys and have a single COL4A gene pair, though often with single isolated COL4 genes similar to those found in C elegans . Remarkably, while the six COL4A genes are conserved in vertebrates, amphibians have lost the COL4A3 and COL4A4 genes. Our findings of the evolutionary emergence of these genes, together with the amphibian double-knockout, opens an experimental window to gain insights into functionality of the Col IV [α345] scaffold.}, } @article {pmid37904088, year = {2023}, author = {Balasubramanian, RN and Gao, M and Umen, J}, title = {Identification of cell-type specific alternative transcripts in the multicellular alga Volvox carteri.}, journal = {BMC genomics}, volume = {24}, number = {1}, pages = {654}, pmid = {37904088}, issn = {1471-2164}, support = {1755430//Division of Integrative Organismal Systems/ ; }, abstract = {BACKGROUND: Cell type specialization is a hallmark of complex multicellular organisms and is usually established through implementation of cell-type-specific gene expression programs. The multicellular green alga Volvox carteri has just two cell types, germ and soma, that have previously been shown to have very different transcriptome compositions which match their specialized roles. Here we interrogated another potential mechanism for differentiation in V. carteri, cell type specific alternative transcript isoforms (CTSAI).

METHODS: We used pre-existing predictions of alternative transcripts and de novo transcript assembly with HISAT2 and Ballgown software to compile a list of loci with two or more transcript isoforms, identified a small subset that were candidates for CTSAI, and manually curated this subset of genes to remove false positives. We experimentally verified three candidates using semi-quantitative RT-PCR to assess relative isoform abundance in each cell type.

RESULTS: Of the 1978 loci with two or more predicted transcript isoforms 67 of these also showed cell type isoform expression biases. After curation 15 strong candidates for CTSAI were identified, three of which were experimentally verified, and their predicted gene product functions were evaluated in light of potential cell type specific roles. A comparison of genes with predicted alternative splicing from Chlamydomonas reinhardtii, a unicellular relative of V. carteri, identified little overlap between ortholog pairs with alternative splicing in both species. Finally, we interrogated cell type expression patterns of 126 V. carteri predicted RNA binding protein (RBP) encoding genes and found 40 that showed either somatic or germ cell expression bias. These RBPs are potential mediators of CTSAI in V. carteri and suggest possible pre-adaptation for cell type specific RNA processing and a potential path for generating CTSAI in the early ancestors of metazoans and plants.

CONCLUSIONS: We predicted numerous instances of alternative transcript isoforms in Volvox, only a small subset of which showed cell type specific isoform expression bias. However, the validated examples of CTSAI supported existing hypotheses about cell type specialization in V. carteri, and also suggested new hypotheses about mechanisms of functional specialization for their gene products. Our data imply that CTSAI operates as a minor but important component of V. carteri cellular differentiation and could be used as a model for how alternative isoforms emerge and co-evolve with cell type specialization.}, } @article {pmid37894891, year = {2023}, author = {Wang, K and Li, W and Cui, H and Qin, S}, title = {Phylogenetic Analysis and Characterization of Diguanylate Cyclase and Phosphodiesterase in Planktonic Filamentous Cyanobacterium Arthrospira sp.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37894891}, issn = {1422-0067}, mesh = {Phosphoric Diester Hydrolases/genetics/metabolism ; *Spirulina/metabolism ; Phylogeny ; Bacterial Proteins/genetics/metabolism ; Escherichia coli/genetics/metabolism ; *Escherichia coli Proteins/genetics/metabolism ; Phosphorus-Oxygen Lyases/genetics/metabolism ; Cyclic GMP/metabolism ; Gene Expression Regulation, Bacterial ; }, abstract = {Cyclic di-GMP (c-di-GMP) is a second messenger of intracellular communication in bacterial species, which widely modulates diverse cellular processes. However, little is known about the c-di-GMP network in filamentous multicellular cyanobacteria. In this study, we preliminarily investigated the c-di-GMP turnover proteins in Arthrospira based on published protein data. Bioinformatics results indicate the presence of at least 149 potential turnover proteins in five Arthrospira subspecies. Some proteins are highly conserved in all tested Arthrospira, whereas others are specifically found only in certain subspecies. To further validate the protein catalytic activity, we constructed a riboswitch-based c-di-GMP expression assay system in Escherichia coli and confirmed that a GGDEF domain protein, Adc11, exhibits potential diguanylate cyclase activity. Moreover, we also evaluated a protein with a conserved HD-GYP domain, Ahd1, the expression of which significantly improved the swimming ability of E. coli. Enzyme-linked immunosorbent assay also showed that overexpression of Ahd1 reduced the intracellular concentration of c-di-GMP, which is presumed to exhibit phosphodiesterase activity. Notably, meta-analyses of transcriptomes suggest that Adc11 and Ahd1 are invariable. Overall, this work confirms the possible existence of a functional c-di-GMP network in Arthrospira, which will provide support for the revelation of the biological function of the c-di-GMP system in Arthrospira.}, } @article {pmid37895205, year = {2023}, author = {Ashouri, A and Zhang, C and Gaiti, F}, title = {Decoding Cancer Evolution: Integrating Genetic and Non-Genetic Insights.}, journal = {Genes}, volume = {14}, number = {10}, pages = {}, doi = {10.3390/genes14101856}, pmid = {37895205}, issn = {2073-4425}, support = {/CAPMC/CIHR/Canada ; }, abstract = {The development of cancer begins with cells transitioning from their multicellular nature to a state akin to unicellular organisms. This shift leads to a breakdown in the crucial regulators inherent to multicellularity, resulting in the emergence of diverse cancer cell subpopulations that have enhanced adaptability. The presence of different cell subpopulations within a tumour, known as intratumoural heterogeneity (ITH), poses challenges for cancer treatment. In this review, we delve into the dynamics of the shift from multicellularity to unicellularity during cancer onset and progression. We highlight the role of genetic and non-genetic factors, as well as tumour microenvironment, in promoting ITH and cancer evolution. Additionally, we shed light on the latest advancements in omics technologies that allow for in-depth analysis of tumours at the single-cell level and their spatial organization within the tissue. Obtaining such detailed information is crucial for deepening our understanding of the diverse evolutionary paths of cancer, allowing for the development of effective therapies targeting the key drivers of cancer evolution.}, } @article {pmid37894679, year = {2023}, author = {Wang, X and Zhang, J and Li, Q and Jia, R and Qiao, M and Cui, W}, title = {In Situ Observation of Cellular Structure Changes in and Chain Segregations of Anabaena sp. PCC 7120 on TiO2 Films under a Photocatalytic Device.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {20}, pages = {}, doi = {10.3390/molecules28207200}, pmid = {37894679}, issn = {1420-3049}, support = {2020GGJS124; YSPTZX202212; 2019xjpy04//Training Plan of Young Backbone Teachers in Universities of Henan Province; the Academician Innovation Center of Hainan Province (Felix Dapare Dakra); Scientific Research Foundation of DeZhou University/ ; }, abstract = {Cyanobacteria outbreaks are serious water pollution events, causing water crises around the world. Photocatalytic disinfection, as an effective approach, has been widely used to inhibit blue algae growth. In this study, a tiny reaction room containing a TiO2 film was designed to fulfill in situ optical observation of the destruction process of a one-dimensional multicellular microorganism, Anabaena sp. PCC 7120, which is also a typical bacterial strain causing water blooms. It was found that the fragment number increased exponentially with the activation time. The fracture mechanics of the algae chains were hypothesized to be the combining functions of increased local tensile stress originated from the cell contracting as well as the oxidative attacks coming from reactive oxygen species (ROSs). It was assumed that the oxidative species were the root cause of cellular structure changes in and chain fractures of Anabaena sp. PCC 7120 in the photocatalytic inactivation activity.}, } @article {pmid37889142, year = {2023}, author = {Pentz, JT and MacGillivray, K and DuBose, JG and Conlin, PL and Reinhardt, E and Libby, E and Ratcliff, WC}, title = {Evolutionary consequences of nascent multicellular life cycles.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, doi = {10.7554/eLife.84336}, pmid = {37889142}, issn = {2050-084X}, support = {T32GM142616/NH/NIH HHS/United States ; }, abstract = {A key step in the evolutionary transition to multicellularity is the origin of multicellular groups as biological individuals capable of adaptation. Comparative work, supported by theory, suggests clonal development should facilitate this transition, although this hypothesis has never been tested in a single model system. We evolved 20 replicate populations of otherwise isogenic clonally reproducing 'snowflake' yeast (Δace2/∆ace2) and aggregative 'floc' yeast (GAL1p::FLO1 /GAL1p::FLO1) with daily selection for rapid growth in liquid media, which favors faster cell division, followed by selection for rapid sedimentation, which favors larger multicellular groups. While both genotypes adapted to this regime, growing faster and having higher survival during the group-selection phase, there was a stark difference in evolutionary dynamics. Aggregative floc yeast obtained nearly all their increased fitness from faster growth, not improved group survival; indicating that selection acted primarily at the level of cells. In contrast, clonal snowflake yeast mainly benefited from higher group-dependent fitness, indicating a shift in the level of Darwinian individuality from cells to groups. Through genome sequencing and mathematical modeling, we show that the genetic bottlenecks in a clonal life cycle also drive much higher rates of genetic drift-a result with complex implications for this evolutionary transition. Our results highlight the central role that early multicellular life cycles play in the process of multicellular adaptation.}, } @article {pmid37888162, year = {2023}, author = {Choi, J and Lee, EJ and Jang, WB and Kwon, SM}, title = {Development of Biocompatible 3D-Printed Artificial Blood Vessels through Multidimensional Approaches.}, journal = {Journal of functional biomaterials}, volume = {14}, number = {10}, pages = {}, doi = {10.3390/jfb14100497}, pmid = {37888162}, issn = {2079-4983}, support = {21A0101L1//Korean Fund for Regenerative Medicine/ ; }, abstract = {Within the human body, the intricate network of blood vessels plays a pivotal role in transporting nutrients and oxygen and maintaining homeostasis. Bioprinting is an innovative technology with the potential to revolutionize this field by constructing complex multicellular structures. This technique offers the advantage of depositing individual cells, growth factors, and biochemical signals, thereby facilitating the growth of functional blood vessels. Despite the challenges in fabricating vascularized constructs, bioprinting has emerged as an advance in organ engineering. The continuous evolution of bioprinting technology and biomaterial knowledge provides an avenue to overcome the hurdles associated with vascularized tissue fabrication. This article provides an overview of the biofabrication process used to create vascular and vascularized constructs. It delves into the various techniques used in vascular engineering, including extrusion-, droplet-, and laser-based bioprinting methods. Integrating these techniques offers the prospect of crafting artificial blood vessels with remarkable precision and functionality. Therefore, the potential impact of bioprinting in vascular engineering is significant. With technological advances, it holds promise in revolutionizing organ transplantation, tissue engineering, and regenerative medicine. By mimicking the natural complexity of blood vessels, bioprinting brings us one step closer to engineering organs with functional vasculature, ushering in a new era of medical advancement.}, } @article {pmid37882538, year = {2023}, author = {Morreale, DP and St Geme Iii, JW and Planet, PJ}, title = {Phylogenomic analysis of the understudied Neisseriaceae species reveals a poly- and paraphyletic Kingella genus.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0312323}, doi = {10.1128/spectrum.03123-23}, pmid = {37882538}, issn = {2165-0497}, abstract = {Taxonomic classification and phylogenetic analysis of the Neisseriaceae family have focused on the pathogens Neisseria meningitidis and Neisseria gonorrhoeae. Less is known about the relationships of commensal Neisseria species and other Neisseriaceae genera, raising the possibility that the phylogeny of this family may not agree with current taxonomy. In this study, we used available nucleotide sequences and a phylogenetic approach to assess the Kingella genus and its relatives. We found that this genus is both paraphyletic and polyphyletic. Kingella potus is more closely related to Neisseria bacilliformis than to other Kingella species. The Alysiella and Simonsiella genera form a distinct clade within the Kingella genus that is closely related to the pathogens K. kingae and K. negevensis. We find a phylogenetic relationship between Conchiformibius, Alysiella, Simonsiella, and Kingella, which we name the CASK clade. Finally, we define the gene sets that differentiate each genus of the CASK clade from one another and from the rest of the Neisseriaceae family. IMPORTANCE Understanding the evolutionary relationships between the species in the Neisseriaceae family has been a persistent challenge in bacterial systematics due to high recombination rates in these species. Previous studies of this family have focused on Neisseria meningitidis and N. gonorrhoeae. However, previously understudied Neisseriaceae species are gaining new attention, with Kingella kingae now recognized as a common human pathogen and with Alysiella and Simonsiella being unique in the bacterial world as multicellular organisms. A better understanding of the genomic evolution of the Neisseriaceae can lead to the identification of specific genes and traits that underlie the remarkable diversity of this family.}, } @article {pmid37874138, year = {2023}, author = {Paterlini, A}, title = {A year at the forefront of plasmodesmal biology.}, journal = {Biology open}, volume = {12}, number = {10}, pages = {}, doi = {10.1242/bio.060123}, pmid = {37874138}, issn = {2046-6390}, abstract = {Cell-cell communication is a central feature of multicellular organisms, enabling division of labour and coordinated responses. Plasmodesmata are membrane-lined pores that provide regulated cytoplasmic continuity between plant cells, facilitating signalling and transport across neighboring cells. Plant development and survival profoundly depend on the existence and functioning of these structures, bringing them to the spotlight for both fundamental and applied research. Despite the rich conceptual and translational rewards in sight, however, the study of plasmodesmata poses significant challenges. This Review will mostly focus on research published between May 2022 and May 2023 and intends to provide a short overview of recent discoveries, innovations, community resources and hypotheses.}, } @article {pmid37849208, year = {2023}, author = {Arenzon, JJ and Peliti, L}, title = {Emergent cooperative behavior in transient compartments.}, journal = {Physical review. E}, volume = {108}, number = {3-1}, pages = {034409}, doi = {10.1103/PhysRevE.108.034409}, pmid = {37849208}, issn = {2470-0053}, mesh = {Humans ; *Cooperative Behavior ; Population Dynamics ; *Game Theory ; Biological Evolution ; }, abstract = {We introduce a minimal model of multilevel selection on structured populations, considering the interplay between game theory and population dynamics. Through a bottleneck process, finite groups are formed with cooperators and defectors sampled from an infinite pool. After the fragmentation, these transient compartments grow until the maximal number of individuals per compartment is attained. Eventually, all compartments are merged and well mixed, and the whole process is repeated. We show that cooperators, even if interacting only through mean-field intragroup interactions that favor defectors, may perform well because of the intergroup competition and the size diversity among the compartments. These cycles of isolation and coalescence may therefore be important in maintaining diversity among different species or strategies and may help to understand the underlying mechanisms of the scaffolding processes in the transition to multicellularity.}, } @article {pmid37865203, year = {2023}, author = {Liu, Y and Liu, Y and Chen, S and Liu, Y and Kong, Z and Guo, Y and Wang, H}, title = {Prenatal exposure to acetaminophen at different doses, courses and time causes testicular dysplasia in offspring mice and its mechanism.}, journal = {Chemosphere}, volume = {}, number = {}, pages = {140496}, doi = {10.1016/j.chemosphere.2023.140496}, pmid = {37865203}, issn = {1879-1298}, abstract = {Epidemiological investigation suggested that the use of acetaminophen during pregnancy may cause offspring testicular dysplasia, but no systematic study has been conducted. In this study, Kunming mice were given acetaminophen at different doses (100/200/400 mg/kg.d), courses (single/multiple), time (second/third trimester) during pregnancy. Fetal blood and testes were collected on gestaional day 18 for detection. The results indicated abnormal testicular development in the PAcE (prenatal acetaminophen exposure) groups. The maximum diameter/cross-sectional area decreased, the interstitial space widened, and decreased proliferation/increased apoptosis were observed, especially in the high-dose, multi-course and second-trimester groups. Meanwhile, the serum testosterone level decreased in PAcE groups, and the steroid synthesis function in Leydig cells, Sertoli and spermatogenic cell function were inhibited, it was more significant in high-dose, multi-course and second-trimester groups. Furthermore, Wnt signal pathway was activated but Notch signal pathway was inhibited in the PAcE groups. Finally, in vitro experiment, acetaminophen could inhibit spermatogonial cell proliferation, enhance apoptosis, and change Wnt/Notch signal pathway. In conclusion, this study confirmed that PAcE can change fetal testicular development in a dose, course and time-dependent manner, and found that multicellular function impaired. This study provides theoretical and experimental basis for systematically elucidating the developmental toxicity of acetaminophen in testis.}, } @article {pmid37863060, year = {2023}, author = {Mishina, T and Chiu, MC and Hashiguchi, Y and Oishi, S and Sasaki, A and Okada, R and Uchiyama, H and Sasaki, T and Sakura, M and Takeshima, H and Sato, T}, title = {Massive horizontal gene transfer and the evolution of nematomorph-driven behavioral manipulation of mantids.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2023.09.052}, pmid = {37863060}, issn = {1879-0445}, abstract = {To complete their life cycle, a wide range of parasites must manipulate the behavior of their hosts.[1] This manipulation is a well-known example of the "extended phenotype,[2]" where genes in one organism have phenotypic effects on another organism. Recent studies have explored the parasite genes responsible for such manipulation of host behavior, including the potential molecular mechanisms.[3][,][4] However, little is known about how parasites have acquired the genes involved in manipulating phylogenetically distinct hosts.[4] In a fascinating example of the extended phenotype, nematomorph parasites have evolved the ability to induce their terrestrial insect hosts to enter bodies of water, where the parasite then reproduces. Here, we comprehensively analyzed nematomorphs and their mantid hosts, focusing on the transcriptomic changes associated with host manipulations and sequence similarity between host and parasite genes to test molecular mimicry. The nematomorph's transcriptome changed during host manipulation, whereas no distinct changes were found in mantids. We then discovered numerous possible host-derived genes in nematomorphs, and these genes were frequently up-regulated during host manipulation. Our findings suggest a possible general role of horizontal gene transfer (HGT) in the molecular mechanisms of host manipulation, as well as in the genome evolution of manipulative parasites. The evidence of HGT between multicellular eukaryotes remains scarce but is increasing and, therefore, elucidating its mechanisms will advance our understanding of the enduring influence of HGT on the evolution of the web of life.}, } @article {pmid37862637, year = {2023}, author = {Yin, S and Mahadevan, L}, title = {Contractility-Induced Phase Separation in Active Solids.}, journal = {Physical review letters}, volume = {131}, number = {14}, pages = {148401}, doi = {10.1103/PhysRevLett.131.148401}, pmid = {37862637}, issn = {1079-7114}, abstract = {Experiments over many decades are suggestive that the combination of cellular contractility and active phase separation in cell-matrix composites can enable spatiotemporal patterning in multicellular tissues across scales. To characterize these phenomena, we provide a general theory that incorporates active cellular contractility into the classical Cahn-Hilliard-Larché model for phase separation in passive viscoelastic solids. Within this framework, we show how a homogeneous cell-matrix mixture can be destabilized by activity via either a pitchfork or Hopf bifurcation, resulting in stable phase separation and/or traveling waves. Numerical simulations of the full equations allow us to track the evolution of the resulting self-organized patterns in periodic and mechanically constrained domains, and in different geometries. Altogether, our study underscores the importance of integrating both cellular activity and mechanical phase separation in understanding patterning in soft, active biosolids in both in vivo and in vitro settings.}, } @article {pmid36824773, year = {2023}, author = {Kapsetaki, SE and Compton, Z and Dolan, J and Harris, VK and Rupp, SM and Duke, EG and Harrison, TM and Aksoy, S and Giraudeau, M and Vincze, O and McGraw, KJ and Aktipis, A and Tollis, M and Boddy, AM and Maley, CC}, title = {Life history and cancer in birds: clutch size predicts cancer.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36824773}, abstract = {Cancer is a disease that affects nearly all multicellular life, including birds. However, little is known about what factors explain the variance in cancer prevalence among species. Litter size is positively correlated with cancer prevalence in managed species of mammals, and larger body size, but not incubation or nestling period, is linked to tumor prevalence in wild birds. Also, birds that produce more elaborate sexual traits are expected to have fewer resources for cancer defenses and thus higher cancer prevalence. In this study, we examined whether cancer prevalence is associated with a wide variety of life history traits (clutch size, incubation length, body mass, lifespan, and the extent of sexual dimorphism) across 108 species of managed birds in 25 different zoological facilities, sanctuaries, and veterinary clinics. We found that clutch size was positively correlated with cancer and neoplasia (both benign and malignant) prevalence, even after controlling for body mass. Cancer prevalence was not associated with incubation length, body mass, lifespan, or sexual dimorphism. The positive correlations of clutch size with cancer prevalence and neoplasia prevalence suggest that there may be life-history trade-offs between reproductive investment and somatic maintenance (in the form of cancer prevention mechanisms) in managed birds.}, } @article {pmid37850657, year = {2023}, author = {Ma, Q and Li, Q and Zheng, X and Pan, J}, title = {CellCommuNet: an atlas of cell-cell communication networks from single-cell RNA sequencing of human and mouse tissues in normal and disease states.}, journal = {Nucleic acids research}, volume = {}, number = {}, pages = {}, doi = {10.1093/nar/gkad906}, pmid = {37850657}, issn = {1362-4962}, support = {CSTB2023NSCQ-MSX0289//Chongqing Medical University/ ; //Natural Science Foundation of Chongqing/ ; BJRC202214//Chongqing Medical University/ ; CXQT21016//University Innovation Research Group Project of Chongqing/ ; W0056//Chongqing Medical University/ ; }, abstract = {Cell-cell communication, as a basic feature of multicellular organisms, is crucial for maintaining the biological functions and microenvironmental homeostasis of cells, organs, and whole organisms. Alterations in cell-cell communication contribute to many diseases, including cancers. Single-cell RNA sequencing (scRNA-seq) provides a powerful method for studying cell-cell communication by enabling the analysis of ligand-receptor interactions. Here, we introduce CellCommuNet (http://www.inbirg.com/cellcommunet/), a comprehensive data resource for exploring cell-cell communication networks in scRNA-seq data from human and mouse tissues in normal and disease states. CellCommuNet currently includes 376 single datasets from multiple sources, and 118 comparison datasets between disease and normal samples originating from the same study. CellCommuNet provides information on the strength of communication between cells and related signalling pathways and facilitates the exploration of differences in cell-cell communication between healthy and disease states. Users can also search for specific signalling pathways, ligand-receptor pairs, and cell types of interest. CellCommuNet provides interactive graphics illustrating cell-cell communication in different states, enabling differential analysis of communication strength between disease and control samples. This comprehensive database aims to be a valuable resource for biologists studying cell-cell communication networks.}, } @article {pmid37848052, year = {2023}, author = {Horinouchi, Y and Togashi, T}, title = {Unicellular and multicellular developmental variations in algal zygotes produce sporophytes.}, journal = {Biology letters}, volume = {19}, number = {10}, pages = {20230313}, doi = {10.1098/rsbl.2023.0313}, pmid = {37848052}, issn = {1744-957X}, abstract = {The emergence of sporophytes, that is, diploid multicellular bodies in plants, facilitated plant diversification and the evolution of complexity. Although sporophytes may have evolved in an ancestral alga exhibiting a haplontic life cycle with a unicellular diploid and multicellular haploid (gametophyte) phase, the mechanism by which this novelty originated remains largely unknown. Ulotrichalean marine green algae (Ulvophyceae) are one of the few extant groups with haplontic-like life cycles. In this study, we show that zygotes of the ulotrichalean alga Monostroma angicava, which usually develop into unicellular cysts, exhibit a developmental variation producing multicellular reproductive sporophytes. Multicellular development likely occurred stochastically in individual zygotes, but its ratio responded plastically to growth conditions. Sporophytes showed identical morphological development to gametophytes, which should reflect the expression of the same genetic programme directing multicellular development. Considering that sporophytes were evolutionarily derived in Ulotrichales, this implies that sporophytes emerged by co-opting the gametophyte developmental programme to the diploid phase. This study suggests a possible mechanism of sporophyte formation in haplontic life cycles, contributing to the understanding of the evolutionary transition from unicellular to multicellular diploid body plans in green plants.}, } @article {pmid37847422, year = {2023}, author = {Baluška, F and Miller, WB and Reber, AS}, title = {Sentient cells as basic units of tissues, organs and organismal physiology.}, journal = {The Journal of physiology}, volume = {}, number = {}, pages = {}, doi = {10.1113/JP284419}, pmid = {37847422}, issn = {1469-7793}, abstract = {Cells evolved some 4 billion years ago, and since then the integrity of the structural and functional continuity of cellular life has been maintained via highly conserved and ancient processes of cell reproduction and division. The plasma membrane as well as all the cytoplasmic structures are reproduced and inherited uninterruptedly by each of the two daughter cells resulting from every cell division. Although our understanding of the evolutionary emergence of the very first cells is obscured by the extremely long timeline since that revolutionary event, the generally accepted position is that the de novo formation of cells is not possible; all present cells are products of other prior cells. This essential biological principle was first discovered by Robert Remak and then effectively coined as Omnis Cellula e Cellula (every cell of the cell) by Rudolf Virchow: all currently living cells have direct structural and functional connections to the very first cells. Based on our previous theoretical analysis, all cells are endowed with individual sentient cognition that guides their individual agency, behaviour and evolution. There is a vital consequence of this new sentient and cognitive view of cells: when cells assemble as functional tissue ecologies and organs within multicellular organisms, including plants, animals and humans, these cellular aggregates display derivative versions of aggregate tissue- and organ-specific sentience and consciousness. This innovative view of the evolution and physiology of all currently living organisms supports a singular principle: all organismal physiology is based on cellular physiology that extends from unicellular roots.}, } @article {pmid37841858, year = {2023}, author = {Kapsetaki, SE and Cisneros, LH and Maley, CC}, title = {Cell-in-cell phenomena across the tree of life.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-3376588/v1}, pmid = {37841858}, abstract = {Cells in obligately multicellular organisms by definition have aligned fitness interests, minimum conflict, and cannot reproduce independently. However, some cells eat other cells within the same body, sometimes called cell cannibalism. Such cell-in-cell events have not been thoroughly discussed in the framework of major transitions to multicellularity. We performed a systematic review of 508 articles to search for cell-in-cell events across the tree of life, the age of cell-in-cell-related genes, and whether cell-in-cell events are associated with normal multicellular development or cancer. Out of the 38 cell-in-cell-related genes found in the literature, 14 genes were over 2.2 billion years old, i.e., older than the common ancestor of some facultatively multicellular taxa. Therefore, we propose that cell-in-cell events originated before the origins of obligate multicellularity. Cell-in-cell events are found almost everywhere: across some unicellular and many multicellular organisms, mostly in malignant rather than benign tissue, and in non-neoplastic cells. Thus, our results show that cell-in-cell events exist in obligate multicellular organisms, but are not a defining feature of them. The idea of eradicating cell-in-cell events from obligate multicellular organisms as a way of treating cancer, without considering that cell-in-cell events are also part of normal development, should be abandoned.}, } @article {pmid37834047, year = {2023}, author = {Borodulina, OR and Ustyantsev, IG and Kramerov, DA}, title = {SINEs as Potential Expression Cassettes: Impact of Deletions and Insertions on Polyadenylation and Lifetime of B2 and Ves SINE Transcripts Generated by RNA Polymerase III.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, doi = {10.3390/ijms241914600}, pmid = {37834047}, issn = {1422-0067}, support = {19-14-00327//Russian Scientific Foundation/ ; }, abstract = {Short Interspersed Elements (SINEs) are common in the genomes of most multicellular organisms. They are transcribed by RNA polymerase III from an internal promoter comprising boxes A and B. As transcripts of certain SINEs from mammalian genomes can be polyadenylated, such transcripts should contain the AATAAA sequence as well as those called β- and τ-signals. One of the goals of this work was to evaluate how autonomous and independent other SINE parts are β- and τ-signals. Extended regions outside of β- and τ-signals were deleted from SINEs B2 and Ves and the derived constructs were used to transfect HeLa cells in order to evaluate the relative levels of their transcripts as well as their polyadenylation efficiency. If the deleted regions affected boxes A and B, the 5'-flanking region of the U6 RNA gene with the external promoter was inserted upstream. Such substitution of the internal promoter in B2 completely restored its transcription. Almost all tested deletions/substitutions did not reduce the polyadenylation capacity of the transcripts, indicating a weak dependence of the function of β- and τ-signals on the neighboring sequences. A similar analysis of B2 and Ves constructs containing a 55-bp foreign sequence inserted between β- and τ-signals showed an equal polyadenylation efficiency of their transcripts compared to those of constructs without the insertion. The acquired poly(A)-tails significantly increased the lifetime and thus the cellular level of such transcripts. The data obtained highlight the potential of B2 and Ves SINEs as cassettes for the expression of relatively short sequences for various applications.}, } @article {pmid37833973, year = {2023}, author = {Hellman, L}, title = {Phenotypic and Functional Heterogeneity of Monocytes and Macrophages.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, doi = {10.3390/ijms241914525}, pmid = {37833973}, issn = {1422-0067}, abstract = {Macrophages are likely to be the first immune cells to have appeared during the evolution of multicellular organisms [...].}, } @article {pmid37832511, year = {2023}, author = {Walker, LM and Sherpa, RN and Ivaturi, S and Brock, DA and Larsen, TJ and Walker, JR and Strassmann, JE and Queller, DC}, title = {Parallel evolution of the G protein-coupled receptor GrlG and the loss of fruiting body formation in the social amoeba Dictyostelium discoideum evolved under low relatedness.}, journal = {G3 (Bethesda, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1093/g3journal/jkad235}, pmid = {37832511}, issn = {2160-1836}, abstract = {Aggregative multicellularity relies on cooperation among formerly independent cells to form a multicellular body. Previous work with Dictyostelium discoideum showed that experimental evolution under low relatedness profoundly decreased cooperation, as indicated by the loss of fruiting body formation in many clones and an increase of cheaters that contribute proportionally more to spores than to the dead stalk. Using whole-genome sequencing and variant analysis of these lines we identified 38 single nucleotide polymorphisms (SNPs) in 29 genes. Each gene had one variant except for grlG (encoding a G protein-coupled receptor), which had ten unique SNPs and five structural variants. Variants in the 5' half of grlG-the region encoding the signal peptide and the extracellular binding domain-were significantly associated with the loss of fruiting body formation; the association was not significant in the 3' half of the gene. These results suggest that the loss of grlG was adaptive under low relatedness and that at least the 5' half of the gene is important for cooperation and multicellular development. This is surprising given some previous evidence that grlG encodes a folate receptor involved in predation, which occurs only during the single-celled stage. However, non-fruiting mutants showed little increase in a parallel evolution experiment where the multicellular stage was prevented from happening. This shows that non-fruiting mutants are not generally selected by any predation advantage, but rather by something - likely cheating - during the multicellular stage.}, } @article {pmid37817595, year = {2023}, author = {Bourke, AFG}, title = {Conflict and conflict resolution in the major transitions.}, journal = {Proceedings. Biological sciences}, volume = {290}, number = {2008}, pages = {20231420}, doi = {10.1098/rspb.2023.1420}, pmid = {37817595}, issn = {1471-2954}, abstract = {Conflict and conflict resolution have been argued to be fundamental to the major transitions in evolution. These were key events in life's history in which previously independently living individuals cooperatively formed a higher-level individual, such as a multicellular organism or eusocial colony. Conflict has its central role because, to proceed stably, the evolution of individuality in each major transition required within-individual conflict to be held in check. This review revisits the role of conflict and conflict resolution in the major transitions, addressing recent work arguing for a minor role. Inclusive fitness logic suggests that differences between the kin structures of clones and sexual families support the absence of conflict at the origin of multicellularity but, by contrast, suggest that key conflicts existed at the origin of eusociality. A principal example is conflict over replacing the founding queen (queen replacement). Following the origin of each transition, conflict remained important, because within-individual conflict potentially disrupts the attainment of maximal individuality (organismality) in the system. The conclusion is that conflict remains central to understanding the major transitions, essentially because conflict arises from differences in inclusive fitness optima while conflict resolution can help the system attain a high degree of coincidence of inclusive fitness interests.}, } @article {pmid37805982, year = {2023}, author = {Germano, DPJ and Zanca, A and Johnston, ST and Flegg, JA and Osborne, JM}, title = {Free and Interfacial Boundaries in Individual-Based Models of Multicellular Biological systems.}, journal = {Bulletin of mathematical biology}, volume = {85}, number = {11}, pages = {111}, doi = {10.1007/s11538-023-01214-8}, pmid = {37805982}, issn = {1522-9602}, support = {DP200100747//Australian Research Council/ ; FT210100034//Australian Research Council/ ; DE200100998//Australian Research Council/ ; }, abstract = {Coordination of cell behaviour is key to a myriad of biological processes including tissue morphogenesis, wound healing, and tumour growth. As such, individual-based computational models, which explicitly describe inter-cellular interactions, are commonly used to model collective cell dynamics. However, when using individual-based models, it is unclear how descriptions of cell boundaries affect overall population dynamics. In order to investigate this we define three cell boundary descriptions of varying complexities for each of three widely used off-lattice individual-based models: overlapping spheres, Voronoi tessellation, and vertex models. We apply our models to multiple biological scenarios to investigate how cell boundary description can influence tissue-scale behaviour. We find that the Voronoi tessellation model is most sensitive to changes in the cell boundary description with basic models being inappropriate in many cases. The timescale of tissue evolution when using an overlapping spheres model is coupled to the boundary description. The vertex model is demonstrated to be the most stable to changes in boundary description, though still exhibits timescale sensitivity. When using individual-based computational models one should carefully consider how cell boundaries are defined. To inform future work, we provide an exploration of common individual-based models and cell boundary descriptions in frequently studied biological scenarios and discuss their benefits and disadvantages.}, } @article {pmid37804416, year = {2023}, author = {Sarabia-Sánchez, MA and Robles-Flores, M}, title = {WNT Signaling in Stem Cells: A Look into the Non-Canonical Pathway.}, journal = {Stem cell reviews and reports}, volume = {}, number = {}, pages = {}, pmid = {37804416}, issn = {2629-3277}, support = {IN229420 and IV200220//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; }, abstract = {Tissue homeostasis is crucial for multicellular organisms, wherein the loss of cells is compensated by generating new cells with the capacity for proliferation and differentiation. At the origin of these populations are the stem cells, which have the potential to give rise to cells with both capabilities, and persevere for a long time through the self-renewal and quiescence. Since the discovery of stem cells, an enormous effort has been focused on learning about their functions and the molecular regulation behind them. Wnt signaling is widely recognized as essential for normal and cancer stem cell. Moreover, β-catenin-dependent Wnt pathway, referred to as canonical, has gained attention, while β-catenin-independent Wnt pathways, known as non-canonical, have remained conspicuously less explored. However, recent evidence about non-canonical Wnt pathways in stem cells begins to lay the foundations of a conceivably vast field, and on which we aim to explain this in the present review. In this regard, we addressed the different aspects in which non-canonical Wnt pathways impact the properties of stem cells, both under normal conditions and also under disease, specifically in cancer.}, } @article {pmid37799611, year = {2023}, author = {Buschi, E and Dell'Anno, A and Tangherlini, M and Stefanni, S and Lo Martire, M and Núñez-Pons, L and Avila, C and Corinaldesi, C}, title = {Rhodobacteraceae dominate the core microbiome of the sea star Odontaster validus (Koehler, 1906) in two opposite geographical sectors of the Antarctic Ocean.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1234725}, pmid = {37799611}, issn = {1664-302X}, abstract = {Microbiota plays essential roles in the health, physiology, and in adaptation of marine multi-cellular organisms to their environment. In Antarctica, marine organisms have a wide range of unique physiological functions and adaptive strategies, useful for coping with extremely cold conditions. However, the role of microbiota associated with Antarctic organisms in such adaptive strategies is underexplored. In the present study, we investigated the diversity and putative functions of the microbiome of the sea star Odontaster validus, one of the main keystone species of the Antarctic benthic ecosystems. We compared the whole-body bacterial microbiome of sea stars from different sites of the Antarctic Peninsula and Ross Sea, two areas located in two opposite geographical sectors of the Antarctic continent. The taxonomic composition of O. validus microbiomes changed both between and within the two Antarctic sectors, suggesting that environmental and biological factors acting both at large and local scales may influence microbiome diversity. Despite this, one bacterial family (Rhodobacteraceae) was shared among all sea star individuals from the two geographical sectors, representing up to 95% of the microbial core, and suggesting a key functional role of this taxon in holobiont metabolism and well-being. In addition, the genus Roseobacter belonging to this family was also present in the surrounding sediment, implying a potential horizontal acquisition of dominant bacterial core taxa via host-selection processes from the environment.}, } @article {pmid37797407, year = {2023}, author = {Paloschi, V and Pauli, J and Winski, G and Wu, Z and Li, Z and Botti, L and Meucci, S and Conti, P and Rogowitz, F and Glukha, N and Hummel, N and Busch, A and Chernogubova, E and Jin, H and Sachs, N and Eckstein, HH and Dueck, A and Boon, RA and Bausch, AR and Maegdefessel, L}, title = {Utilization of an Artery-on-a-chip to Unravel Novel Regulators and Therapeutic Targets in Vascular Diseases.}, journal = {Advanced healthcare materials}, volume = {}, number = {}, pages = {e2302907}, doi = {10.1002/adhm.202302907}, pmid = {37797407}, issn = {2192-2659}, abstract = {In this study, organ-on-chip technology is used to develop an in vitro model of medium-to-large size arteries, the artery-on-a-chip (AoC), with the objective to recapitulate the structure of the arterial wall and the relevant hemodynamic forces affecting luminal cells. AoCs exposed either to in vivo-like shear stress values or kept in static conditions are assessed to generate a panel of novel genes modulated by shear stress. Considering the crucial role played by shear stress alterations in carotid arteries affected by atherosclerosis (CAD) and abdominal aortic aneurysms (AAA) disease development/progression, a patient cohort of hemodynamically relevant specimens was utilized, consisting of diseased and non-diseased (internal control) vessel regions from the same patient. Genes activated by shear stress followed the same expression pattern in non-diseased segments of human vessels. Single cell RNA sequencing enables us to discriminate the unique cell subpopulations between non-diseased and diseased vessel portions, revealing an enrichment of flow activated genes in structural cells originating from non-diseased specimens. Furthermore, the AoC served as a platform for drug-testing. It reproduced the effects of a therapeutic agent (lenvatinib) previously used in preclinical AAA studies, therefore extending our understanding of its therapeutic effect through a multicellular structure. This article is protected by copyright. All rights reserved.}, } @article {pmid37783374, year = {2023}, author = {Igamberdiev, AU and Gordon, R}, title = {Macroevolution, differentiation trees, and the growth of coding systems.}, journal = {Bio Systems}, volume = {}, number = {}, pages = {105044}, doi = {10.1016/j.biosystems.2023.105044}, pmid = {37783374}, issn = {1872-8324}, abstract = {An open process of evolution of multicellular organisms is based on the rearrangement and growth of the program of differentiation that underlies biological morphogenesis. The maintenance of the final (adult) stable non-equilibrium state (stasis) of a developmental system determines the direction of the evolutionary process. This state is achieved via the sequence of differentiation events representable as differentiation trees. A special type of morphogenetic code, acting as a metacode governing gene expression, may include electromechanical signals appearing as differentiation waves. The excessive energy due to the incorporation of mitochondria in eukaryotic cells resulted not only in more active metabolism but also in establishing the differentiation code for interconnecting cells and forming tissues, which fueled the evolutionary process. The "invention" of "continuing differentiation" distinguishes multicellular eukaryotes from multicellular prokaryotes. The Janus-faced control, involving both top-down control by differentiation waves and bottom-up control via the mechanical consequences of cell differentiations, underlies the process of morphogenesis and results in the achievement of functional stable final states. Duplications of branches of the differentiation tree may be the basis for continuing differentiation and macroevolution, analogous to gene duplication permitting divergence of genes. Metamorphoses, if they are proven to be fusions of disparate species, may be classified according to the topology of fusions of two differentiation trees. In the process of unfolding of morphogenetic structures, microevolution can be defined as changes of the differentiation tree that preserve topology of the tree, while macroevolution represents any change that alters the topology of the differentiation tree.}, } @article {pmid37765506, year = {2023}, author = {Wegner, L and Porth, ML and Ehlers, K}, title = {Multicellularity and the Need for Communication-A Systematic Overview on (Algal) Plasmodesmata and Other Types of Symplasmic Cell Connections.}, journal = {Plants (Basel, Switzerland)}, volume = {12}, number = {18}, pages = {}, doi = {10.3390/plants12183342}, pmid = {37765506}, issn = {2223-7747}, support = {EH 372/1-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {In the evolution of eukaryotes, the transition from unicellular to simple multicellular organisms has happened multiple times. For the development of complex multicellularity, characterized by sophisticated body plans and division of labor between specialized cells, symplasmic intercellular communication is supposed to be indispensable. We review the diversity of symplasmic connectivity among the eukaryotes and distinguish between distinct types of non-plasmodesmatal connections, plasmodesmata-like structures, and 'canonical' plasmodesmata on the basis of developmental, structural, and functional criteria. Focusing on the occurrence of plasmodesmata (-like) structures in extant taxa of fungi, brown algae (Phaeophyceae), green algae (Chlorophyta), and streptophyte algae, we present a detailed critical update on the available literature which is adapted to the present classification of these taxa and may serve as a tool for future work. From the data, we conclude that, actually, development of complex multicellularity correlates with symplasmic connectivity in many algal taxa, but there might be alternative routes. Furthermore, we deduce a four-step process towards the evolution of canonical plasmodesmata and demonstrate similarity of plasmodesmata in streptophyte algae and land plants with respect to the occurrence of an ER component. Finally, we discuss the urgent need for functional investigations and molecular work on cell connections in algal organisms.}, } @article {pmid37748879, year = {2023}, author = {Kurakin, G}, title = {Lipoxygenase in a Giant Sulfur Bacterium: An Evolutionary Solution for Size and Complexity?.}, journal = {Biochemistry. Biokhimiia}, volume = {88}, number = {6}, pages = {842-845}, doi = {10.1134/S0006297923060111}, pmid = {37748879}, issn = {1608-3040}, mesh = {*Lipoxygenase/genetics ; *Lipoxygenases ; Biological Evolution ; Bacteria ; Sulfur ; }, abstract = {Discovery of Thiomargarita magnifica - an exceptionally large giant sulfur bacterium - urges us to pay additional attention to the giant sulfur bacteria and to revisit our recent bioinformatic finding of lipoxygenases in the representatives of the genus Beggiatoa. These close relatives of Thiomargarita magnifica meet the similar size requirements by forming multicellular structures. We hypothesize that their lipoxygenases are a part of the oxylipin signaling system that provides high level of cell-to-cell signaling complexity which, in turn, enables them to reach large sizes.}, } @article {pmid37747940, year = {2023}, author = {Murali, R and Yu, H and Speth, DR and Wu, F and Metcalfe, KS and Crémière, A and Laso-Pèrez, R and Malmstrom, RR and Goudeau, D and Woyke, T and Hatzenpichler, R and Chadwick, GL and Connon, SA and Orphan, VJ}, title = {Physiological potential and evolutionary trajectories of syntrophic sulfate-reducing bacterial partners of anaerobic methanotrophic archaea.}, journal = {PLoS biology}, volume = {21}, number = {9}, pages = {e3002292}, doi = {10.1371/journal.pbio.3002292}, pmid = {37747940}, issn = {1545-7885}, abstract = {Sulfate-coupled anaerobic oxidation of methane (AOM) is performed by multicellular consortia of anaerobic methanotrophic (ANME) archaea in obligate syntrophic partnership with sulfate-reducing bacteria (SRB). Diverse ANME and SRB clades co-associate but the physiological basis for their adaptation and diversification is not well understood. In this work, we used comparative metagenomics and phylogenetics to investigate the metabolic adaptation among the 4 main syntrophic SRB clades (HotSeep-1, Seep-SRB2, Seep-SRB1a, and Seep-SRB1g) and identified features associated with their syntrophic lifestyle that distinguish them from their non-syntrophic evolutionary neighbors in the phylum Desulfobacterota. We show that the protein complexes involved in direct interspecies electron transfer (DIET) from ANME to the SRB outer membrane are conserved between the syntrophic lineages. In contrast, the proteins involved in electron transfer within the SRB inner membrane differ between clades, indicative of convergent evolution in the adaptation to a syntrophic lifestyle. Our analysis suggests that in most cases, this adaptation likely occurred after the acquisition of the DIET complexes in an ancestral clade and involve horizontal gene transfers within pathways for electron transfer (CbcBA) and biofilm formation (Pel). We also provide evidence for unique adaptations within syntrophic SRB clades, which vary depending on the archaeal partner. Among the most widespread syntrophic SRB, Seep-SRB1a, subclades that specifically partner ANME-2a are missing the cobalamin synthesis pathway, suggestive of nutritional dependency on its partner, while closely related Seep-SRB1a partners of ANME-2c lack nutritional auxotrophies. Our work provides insight into the features associated with DIET-based syntrophy and the adaptation of SRB towards it.}, } @article {pmid37743376, year = {2023}, author = {Zhang, Z and Huo, W and Wang, X and Ren, Z and Zhao, J and Liu, Y and He, K and Zhang, F and Li, W and Jin, S and Yang, D}, title = {Origin, evolution, and diversification of the wall-associated kinase gene family in plants.}, journal = {Plant cell reports}, volume = {}, number = {}, pages = {}, pmid = {37743376}, issn = {1432-203X}, support = {232300421116//Natural Science Foundation of Henan Province/ ; }, abstract = {The study of the origin, evolution, and diversification of the wall-associated kinase gene family in plants facilitates their functional investigations in the future. Wall-associated kinases (WAKs) make up one subfamily of receptor-like kinases (RLKs), and function directly in plant cell elongation and responses to biotic and abiotic stresses. The biological functions of WAKs have been extensively characterized in angiosperms; however, the origin and evolutionary history of the WAK family in green plants remain unclear. Here, we performed a comprehensive analysis of the WAK family to reveal its origin, evolution, and diversification in green plants. In total, 1061 WAK genes were identified in 37 species from unicellular algae to multicellular plants, and the results showed that WAK genes probably originated before bryophyte differentiation and were widely distributed in land plants, especially angiosperms. The phylogeny indicated that the land plant WAKs gave rise to five clades and underwent lineage-specific expansion after species differentiation. Cis-acting elements and expression patterns analyses of WAK genes in Arabidopsis and rice demonstrated the functional diversity of WAK genes in these two species. Many gene gains and losses have occurred in angiosperms, leading to an increase in the number of gene copies. The evolutionary trajectory of the WAK family during polyploidization was uncovered using Gossypium species. Our results provide insights into the evolution of WAK genes in green plants, facilitating their functional investigations in the future.}, } @article {pmid37741353, year = {2023}, author = {Ma, C and Li, X and Xiao, H and Li, B and Gu, H and Guo, Y and Wang, H and Wen, Y and Chen, L}, title = {Course-, dose-, and stage-dependent toxic effects of prenatal acetaminophen exposure on fetal long bone development.}, journal = {Toxicology letters}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.toxlet.2023.09.007}, pmid = {37741353}, issn = {1879-3169}, abstract = {Acetaminophen is a common analgesic and fever reduction medicine for pregnant women. Epidemiological studies suggest that prenatal acetaminophen usage affects offspring health and development. However, the effects of prenatal acetaminophen exposure (PAcE) on fetal long bone development and its potential mechanisms have not been elucidated. Based on clinical dosing characteristics, fetal mouse femurs were obtained for detection after oral gavage of acetaminophen at different doses (0, 100 or 400mg/kg d), courses (single or multiple times) or stages (mid- or late pregnancy) during pregnancy in Kunming mice. The results showed that compared with the control group, PAcE reduced the length of total femur and the primary ossification center (POC), delayed the mineralization of POC and the ossification of epiphyseal region, and down-regulated the mRNA expression of osteogenic function markers (such as Runx2, Bsp, Ocn, Col1a1) in fetal femur, particularly in the high dose, multiple courses, and mid-pregnancy group. Meanwhile, the osteoclast and angiogenic function were also inhibited by PAcE at high dose, multiple courses, and mid-pregnancy, but the inhibition level was less than osteogenic function. Moreover, the alteration of canonical Wnt signalling pathway in PAcE fetal bone were consistent with its osteogenesis function changes. In conclusion, PAcE caused development toxicity and multi-cellular function inhibition in fetal long bone, particularly in the high dose, multiple treatments and mid-pregnancy group, and the alteration of canonical Wnt signalling pathway may be its potential mechanism.}, } @article {pmid37727796, year = {2023}, author = {Craig, JM and Kumar, S and Hedges, SB}, title = {The origin of eukaryotes and rise in complexity were synchronous with the rise in oxygen.}, journal = {Frontiers in bioinformatics}, volume = {3}, number = {}, pages = {1233281}, pmid = {37727796}, issn = {2673-7647}, abstract = {The origin of eukaryotes was among the most important events in the history of life, spawning a new evolutionary lineage that led to all complex multicellular organisms. However, the timing of this event, crucial for understanding its environmental context, has been difficult to establish. The fossil and biomarker records are sparse and molecular clocks have thus far not reached a consensus, with dates spanning 2.1-0.91 billion years ago (Ga) for critical nodes. Notably, molecular time estimates for the last common ancestor of eukaryotes are typically hundreds of millions of years younger than the Great Oxidation Event (GOE, 2.43-2.22 Ga), leading researchers to question the presumptive link between eukaryotes and oxygen. We obtained a new time estimate for the origin of eukaryotes using genetic data of both archaeal and bacterial origin, the latter rarely used in past studies. We also avoided potential calibration biases that may have affected earlier studies. We obtained a conservative interval of 2.2-1.5 Ga, with an even narrower core interval of 2.0-1.8 Ga, for the origin of eukaryotes, a period closely aligned with the rise in oxygen. We further reconstructed the history of biological complexity across the tree of life using three universal measures: cell types, genes, and genome size. We found that the rise in complexity was temporally consistent with and followed a pattern similar to the rise in oxygen. This suggests a causal relationship stemming from the increased energy needs of complex life fulfilled by oxygen.}, } @article {pmid37727086, year = {2023}, author = {Kalambokidis, M and Travisano, M}, title = {Multispecies interactions shape the transition to multicellularity.}, journal = {Proceedings. Biological sciences}, volume = {290}, number = {2007}, pages = {20231055}, doi = {10.1098/rspb.2023.1055}, pmid = {37727086}, issn = {1471-2954}, abstract = {The origin of multicellularity transformed the adaptive landscape on Earth, opening diverse avenues for further innovation. The transition to multicellular life is understood as the evolution of cooperative groups which form a new level of individuality. Despite the potential for community-level interactions, most studies have not addressed the competitive context of this transition, such as competition between species. Here, we explore how interspecific competition shapes the emergence of multicellularity in an experimental system with two yeast species, Saccharomyces cerevisiae and Kluyveromyces lactis, where multicellularity evolves in response to selection for faster settling ability. We find that the multispecies context slows the rate of the transition to multicellularity, and the transition to multicellularity significantly impacts community composition. Multicellular K. lactis emerges first and sweeps through populations in monocultures faster than in cocultures with S. cerevisiae. Following the transition, the between-species competitive dynamics shift, likely in part to intraspecific cooperation in K. lactis. Hence, we document an eco-evolutionary feedback across the transition to multicellularity, underscoring how ecological context is critical for understanding the causes and consequences of innovation. By including two species, we demonstrate that cooperation and competition across several biological scales shapes the origin and persistence of multicellularity.}, } @article {pmid37722687, year = {2023}, author = {Kulkarni, M and Hardwick, JM}, title = {Programmed Cell Death in Unicellular Versus Multicellular Organisms.}, journal = {Annual review of genetics}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-genet-033123-095833}, pmid = {37722687}, issn = {1545-2948}, abstract = {Programmed cell death (self-induced) is intrinsic to all cellular life forms, including unicellular organisms. However, cell death research has focused on animal models to understand cancer, degenerative disorders, and developmental processes. Recently delineated suicidal death mechanisms in bacteria and fungi have revealed ancient origins of animal cell death that are intertwined with immune mechanisms, allaying earlier doubts that self-inflicted cell death pathways exist in microorganisms. Approximately 20 mammalian death pathways have been partially characterized over the last 35 years. By contrast, more than 100 death mechanisms have been identified in bacteria and a few fungi in recent years. However, cell death is nearly unstudied in most human pathogenic microbes that cause major public health burdens. Here, we consider how the current understanding of programmed cell death arose through animal studies and how recently uncovered microbial cell death mechanisms in fungi and bacteria resemble and differ from mechanisms of mammalian cell death. Expected final online publication date for the Annual Review of Genetics, Volume 57 is November 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, } @article {pmid37699344, year = {2023}, author = {Azimzadeh, J and Durand, B}, title = {Evolution: The ancient history of cilia assembly regulation.}, journal = {Current biology : CB}, volume = {33}, number = {17}, pages = {R898-R900}, doi = {10.1016/j.cub.2023.07.053}, pmid = {37699344}, issn = {1879-0445}, abstract = {A new study identifies a conserved regulatory mechanism for cilia assembly in the closest unicellular relatives of animals, suggesting that this mechanism was already present in a common unicellular ancestor and was repurposed during the transition to multicellularity.}, } @article {pmid37679778, year = {2023}, author = {Johnson, GA and Burghardt, RC and Bazer, FW and Seo, H and Cain, JW}, title = {Integrins and their potential roles in mammalian pregnancy.}, journal = {Journal of animal science and biotechnology}, volume = {14}, number = {1}, pages = {115}, pmid = {37679778}, issn = {1674-9782}, support = {98-35203-6337//National Institute of Food and Agriculture/ ; 2006-35203-17199//National Institute of Food and Agriculture/ ; 2012-67011-19892//National Institute of Food and Agriculture/ ; 2016-67015-24955//National Institute of Food and Agriculture/ ; 1-F32-HDO 8501 O1A1//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; 1R21HD071468-01//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; }, abstract = {Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix (ECM) interactions leading to assembly of integrin adhesion complexes (IACs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus (embryo/fetus and associated placental membranes) development. This review provides a succinct overview of integrin structure, ligand binding, and signaling followed with a concise overview of embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example for rodents. A brief timeline of the initial localization of integrin subunits to the uterine luminal epithelium (LE) and conceptus trophoblast is then presented, followed by sequential summaries of integrin expression and function during gestation in pigs, sheep, humans, and rodents. As appropriate for this journal, summaries of integrin expression and function during gestation in pigs and sheep are in depth, whereas summaries for humans and rodents are brief. Because similar models to those illustrated in Fig. 1, 2, 3, 4, 5 and 6 are present throughout the scientific literature, the illustrations in this manuscript are drafted as Viking imagery for entertainment purposes.}, } @article {pmid37675460, year = {2023}, author = {Chevalier, RL}, title = {Why is chronic kidney disease progressive? Evolutionary adaptations and maladaptations.}, journal = {American journal of physiology. Renal physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajprenal.00134.2023}, pmid = {37675460}, issn = {1522-1466}, abstract = {Despite significant advances in renal physiology, the global prevalence of chronic kidney disease (CKD) continues to increase. The emergence of multicellular organisms gave rise to increasing complexity of life resulting in tradeoffs reflecting ancestral adaptations to changing environments. Three evolutionary traits shape CKD over the lifespan: 1) variation in nephron number at birth, 2) progressive nephron loss with aging, and 3) adaptive kidney growth in response to decreased nephron number. Although providing plasticity in adaptation to changing environments, the cell cycle must function within constraints dictated by available energy. Prioritized allocation of energy available through the placenta can restrict fetal nephrogenesis, a risk factor for CKD. Moreover, nephron loss with aging is a consequence of cell senescence, a pathway accelerated by adaptive nephron hypertrophy that maintains metabolic homeostasis at the expense of increased vulnerability to stressors. Driven by reproductive fitness, natural selection operates in early life, but diminishes thereafter, leading to an exponential increase in CKD with aging, a product of antagonistic pleiotropy. A deeper understanding of the evolutionary constraints on the cell cycle may lead to manipulation of the balance between progenitor cell renewal and differentiation, regulation of cell senescence, and modulation of the balance between cell proliferation and hypertrophy. Application of an evolutionary perspective may enhance understanding of adaptation and maladaptation by nephrons in the progression of CKD, leading to new therapeutic advances.}, } @article {pmid37668864, year = {2023}, author = {Garte, S}, title = {Targeted Hypermutation as a Survival Strategy: A Theoretical Approach.}, journal = {Acta biotheoretica}, volume = {71}, number = {4}, pages = {20}, pmid = {37668864}, issn = {1572-8358}, abstract = {Targeted hypermutation has proven to be a useful survival strategy for bacteria under severe stress and is also used by multicellular organisms in specific instances such as the mammalian immune system. This might appear surprising, given the generally observed deleterious effects of poor replication fidelity/high mutation rate. A previous theoretical model designed to explore the role of replication fidelity in the origin of life was applied to a simulated hypermutation scenario. The results confirmed that the same model is useful for analyzing hypermutation and can predict the effects of the same parameters (survival probability, replication fidelity, mutation effect, and others) on the survival of cellular populations undergoing hypermutation as a result of severe stress.}, } @article {pmid37666963, year = {2023}, author = {Clark, JW and Hetherington, AJ and Morris, JL and Pressel, S and Duckett, JG and Puttick, MN and Schneider, H and Kenrick, P and Wellman, CH and Donoghue, PCJ}, title = {Evolution of phenotypic disparity in the plant kingdom.}, journal = {Nature plants}, volume = {}, number = {}, pages = {}, pmid = {37666963}, issn = {2055-0278}, support = {NE/N002067/1//RCUK | Natural Environment Research Council (NERC)/ ; NE/P013678/1//RCUK | Natural Environment Research Council (NERC)/ ; NE/N002067/1//RCUK | Natural Environment Research Council (NERC)/ ; NE/N002067/1//RCUK | Natural Environment Research Council (NERC)/ ; NE/N002067/1//RCUK | Natural Environment Research Council (NERC)/ ; NE/N002067/1//RCUK | Natural Environment Research Council (NERC)/ ; NE/N002067/1//RCUK | Natural Environment Research Council (NERC)/ ; NE/N002067/1//RCUK | Natural Environment Research Council (NERC)/ ; NE/N002067/1//RCUK | Natural Environment Research Council (NERC)/ ; BB/N000919/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; BB/T012773/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; RF-2022-167//Leverhulme Trust/ ; RPG-2019-004//Leverhulme Trust/ ; JTF 62574//John Templeton Foundation (JTF)/ ; }, abstract = {The plant kingdom exhibits diverse bodyplans, from single-celled algae to complex multicellular land plants, but it is unclear how this phenotypic disparity was achieved. Here we show that the living divisions comprise discrete clusters within morphospace, separated largely by reproductive innovations, the extinction of evolutionary intermediates and lineage-specific evolution. Phenotypic complexity correlates not with disparity but with ploidy history, reflecting the role of genome duplication in plant macroevolution. Overall, the plant kingdom exhibits a pattern of episodically increasing disparity throughout its evolutionary history that mirrors the evolutionary floras and reflects ecological expansion facilitated by reproductive innovations. This pattern also parallels that seen in the animal and fungal kingdoms, suggesting a general pattern for the evolution of multicellular bodyplans.}, } @article {pmid37664459, year = {2023}, author = {Marotta, P and Ruggiero, A and Bilcke, G}, title = {Editorial: Unicellular organisms as an evolutionary snapshot toward multicellularity.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1254636}, pmid = {37664459}, issn = {2296-634X}, } @article {pmid36993598, year = {2023}, author = {Barker-Clarke, RJ and Gray, JM and Tadele, DS and Hinczewski, M and Scott, JG}, title = {Maintaining, masking, and mimicking selection: the interplay of cell-intrinsic and cell-extrinsic effects upon eco-evolutionary dynamics.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.03.15.532871}, pmid = {36993598}, support = {R37 CA244613/CA/NCI NIH HHS/United States ; }, abstract = {Evolution is a stochastic yet inevitable process that lies at the heart of biology yet in the multi-cellular environments within patients, ecological complexities arise via heterogeneity and microenvironments. The interplay of ecology and mutation is thus fundamental to predicting the evolution of complex diseases and engineering optimal treatment solutions. As experimental evidence of ecological interactions between disease agents continues to grow, so does the need for evolutionary theory and modeling that incorporates these interaction effects. Inspired by experimental cell biology, we transform the variables in the interaction payoff matrix to encode cell-cell interactions in our mathematical approach as growth-rate modifying, frequency-dependent interactions. In this way, we can show the extent to which the presence of these cell-extrinsic ecological interactions can modify the evolutionary trajectories that would be predicted from cell-intrinsic properties alone. To do this we form a Fokker-Planck equation for a genetic population undergoing diffusion, drift, and interactions and generate a novel, analytic solution for the stationary distribution. We use this solution to determine when these interactions can modify evolution in such ways as to maintain, mask, or mimic mono-culture fitness differences. This work has implications for the interpretation and understanding of experimental and patient evolution and is a result that may help to explain the abundance of apparently neutral evolution in cancer systems and heterogeneous populations in general. In addition, the derivation of an analytical result for stochastic, ecologically dependent evolution paves the way for treatment approaches requiring knowledge of a stationary solution for the development of control protocols.}, } @article {pmid37649301, year = {2023}, author = {Borg, M and Krueger-Hadfield, SA and Destombe, C and Collén, J and Lipinska, A and Coelho, SM}, title = {Red macroalgae in the genomic era.}, journal = {The New phytologist}, volume = {}, number = {}, pages = {}, doi = {10.1111/nph.19211}, pmid = {37649301}, issn = {1469-8137}, support = {//Bettencourt Schuller Foundation/ ; //Gordon and Betty Moore Foundation/ ; 864038//H2020 European Research Council/ ; DEB-2141971//National Science Foundation/ ; //Max Planck Society/ ; }, abstract = {Rhodophyta (or red algae) are a diverse and species-rich group that forms one of three major lineages in the Archaeplastida, a eukaryotic supergroup whose plastids arose from a single primary endosymbiosis. Red algae are united by several features, such as relatively small intron-poor genomes and a lack of cytoskeletal structures associated with motility like flagella and centrioles, as well as a highly efficient photosynthetic capacity. Multicellular red algae (or macroalgae) are one of the earliest diverging eukaryotic lineages to have evolved complex multicellularity, yet despite their ecological, evolutionary, and commercial importance, they have remained a largely understudied group of organisms. Considering the increasing availability of red algal genome sequences, we present a broad overview of fundamental aspects of red macroalgal biology and posit on how this is expected to accelerate research in many domains of red algal biology in the coming years.}, } @article {pmid37645274, year = {2022}, author = {Hall, G and Kelly, S and Schaap, P and Schilde, C}, title = {Phylogeny-wide analysis of G-protein coupled receptors in social amoebas and implications for the evolution of multicellularity.}, journal = {Open research Europe}, volume = {2}, number = {}, pages = {134}, pmid = {37645274}, issn = {2732-5121}, abstract = {G-protein coupled receptors (GPCRs) are seven-transmembrane proteins and constitute the largest group of receptors within eukaryotes. The presence of a large set of GPCRs in the unicellular Amoebozoa was surprising and is indicative of the largely undiscovered environmental sensing capabilities in this group. Evolutionary transitions from unicellular to multicellular lifestyles, like we see in social amoebas, have occurred several times independently in the Amoebozoa, and GPCRs may have been co-opted for new functions in cell-cell communication. Methods We have analysed a set of GPCRs from fully sequenced Amoebozoan genomes by Bayesian inference, compared their phylogenetic distribution and domain composition, and analysed their temporal and spatial expression patterns in five species of dictyostelids. Results We found evidence that most GPCRs are conserved deeply in the Amoebozoa and are probably performing roles in general cell functions and complex environmental sensing. All families of GPCRs (apart from the family 4 fungal pheromone receptors) are present in dictyostelids with family 5 being the largest and family 2 the one with the fewest members. For the first time, we identify the presence of family 1 rhodopsin-like GPCRs in dictyostelids. Some GPCRs have been amplified in the dictyostelids and in specific lineages thereof and through changes in expression patterns may have been repurposed for signalling in multicellular development. Discussion Our phylogenetic analysis suggests that GPCR families 1, 2 and 6 already diverged early in the Amoebozoa, whereas families 3 and 5 expanded later within the dictyostelids. The family 6 cAMP receptors that have experimentally supported roles in multicellular development in dictyostelids (carA-carD; tasA/B) originated at the root of all dictyostelids and only have weakly associated homologs in Physarum polycephalum. Our analysis identified candidate GPCRs which have evolved in the dictyostelids and could have been co-opted for multicellular development.}, } @article {pmid37628687, year = {2023}, author = {Zamani-Dahaj, SA and Burnetti, A and Day, TC and Yunker, PJ and Ratcliff, WC and Herron, MD}, title = {Spontaneous Emergence of Multicellular Heritability.}, journal = {Genes}, volume = {14}, number = {8}, pages = {}, doi = {10.3390/genes14081635}, pmid = {37628687}, issn = {2073-4425}, support = {GM138030/GM/NIGMS NIH HHS/United States ; NNA17BB05A/NASA/NASA/United States ; }, abstract = {The major transitions in evolution include events and processes that result in the emergence of new levels of biological individuality. For collectives to undergo Darwinian evolution, their traits must be heritable, but the emergence of higher-level heritability is poorly understood and has long been considered a stumbling block for nascent evolutionary transitions. Using analytical models, synthetic biology, and biologically-informed simulations, we explored the emergence of trait heritability during the evolution of multicellularity. Prior work on the evolution of multicellularity has asserted that substantial collective-level trait heritability either emerges only late in the transition or requires some evolutionary change subsequent to the formation of clonal multicellular groups. In a prior analytical model, we showed that collective-level heritability not only exists but is usually more heritable than the underlying cell-level trait upon which it is based, as soon as multicellular groups form. Here, we show that key assumptions and predictions of that model are borne out in a real engineered biological system, with important implications for the emergence of collective-level heritability.}, } @article {pmid37620617, year = {2023}, author = {Savageau, MA}, title = {Phenotype Design Space Provides a Mechanistic Framework Relating Molecular Parameters to Phenotype Diversity Available for Selection.}, journal = {Journal of molecular evolution}, volume = {}, number = {}, pages = {}, pmid = {37620617}, issn = {1432-1432}, support = {MCB 1716833//National Science Foundation/ ; }, abstract = {Two long-standing challenges in theoretical population genetics and evolution are predicting the distribution of phenotype diversity generated by mutation and available for selection, and determining the interaction of mutation, selection and drift to characterize evolutionary equilibria and dynamics. More fundamental for enabling such predictions is the current inability to causally link genotype to phenotype. There are three major mechanistic mappings required for such a linking - genetic sequence to kinetic parameters of the molecular processes, kinetic parameters to biochemical system phenotypes, and biochemical phenotypes to organismal phenotypes. This article introduces a theoretical framework, the Phenotype Design Space (PDS) framework, for addressing these challenges by focusing on the mapping of kinetic parameters to biochemical system phenotypes. It provides a quantitative theory whose key features include (1) a mathematically rigorous definition of phenotype based on biochemical kinetics, (2) enumeration of the full phenotypic repertoire, and (3) functional characterization of each phenotype independent of its context-dependent selection or fitness contributions. This framework is built on Design Space methods that relate system phenotypes to genetically determined parameters and environmentally determined variables. It also has the potential to automate prediction of phenotype-specific mutation rate constants and equilibrium distributions of phenotype diversity in microbial populations undergoing steady-state exponential growth, which provides an ideal reference to which more realistic cases can be compared. Although the framework is quite general and flexible, the details will undoubtedly differ for different functions, organisms and contexts. Here a hypothetical case study involving a small molecular system, a primordial circadian clock, is used to introduce this framework and to illustrate its use in a particular case. The framework is built on fundamental biochemical kinetics. Thus, the foundation is based on linear algebra and reasonable physical assumptions, which provide numerous opportunities for experimental testing and further elaboration to deal with complex multicellular organisms that are currently beyond its scope. The discussion provides a comparison of results from the PDS framework with those from other approaches in theoretical population genetics.}, } @article {pmid37620056, year = {2023}, author = {Li, XG and Dai, J and Zhang, WJ and Jiang, AJ and Li, DH and Wu, LF}, title = {Genome analysis of Tepidibacter sp. SWIR-1, an anaerobic endospore-forming bacterium isolated from a deep-sea hydrothermal vent.}, journal = {Marine genomics}, volume = {71}, number = {}, pages = {101049}, doi = {10.1016/j.margen.2023.101049}, pmid = {37620056}, issn = {1876-7478}, abstract = {Tepidibacter sp. SWIR-1, a putative new species isolated from deep-sea hydrothermal vent field on the Southwest Indian Ridge (SWIR), is an anaerobic, mesophilic and endospore-forming bacterium belonging to the family Peptostreptococcaceae. In this study, we present the complete genome sequence of strain SWIR-1, consists of a single circular chromosome comprising 4,122,966 nucleotides with 29.25% G + C content and a circular plasmid comprising 38,843 nucleotides with 29.46% G + C content. In total, 3861 protein coding genes, 104 tRNA genes and 46 rRNA genes were obtained. SWIR-1 genome contains numerous genes related to sporulation and germination. Compared with the other three Tepidibacter species, SWIR-1 contained more spore germination receptor proteins. In addition, SWIR-1 contained more genes involved in chemotaxis and two-component systems than other Tepidibacter species. These results indicated that SWIR-1 has developed versatile adaptability to the Southwest Indian Ridge hydrothermal vent environment. The genome of strain SWIR-1 will be helpful for further understanding adaptive strategies used by bacteria dwelling in the deep-sea hydrothermal vent environments of different oceans.}, } @article {pmid37609247, year = {2023}, author = {Kasimatis, KR and Willis, JH and Phillips, PC}, title = {Post-insemination sexual selection in males indirectly masculinizes the female transcriptome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.08.09.552689}, pmid = {37609247}, abstract = {UNLABELLED: Sex-specific regulation of gene expression is the most plausible way for generating sexually differentiated phenotypes from an essentially shared genome. However, since genetic material is shared, sex-specific selection in one sex can have an indirect response in the other sex. From a gene expression perspective, this tethered response can move one sex away from their wildtype expression state and impact potentially many gene regulatory networks. Here, using experimental evolution in the model nematode Caenorhabditis elegans , we explore the coupling of direct sexual selection on males with the transcriptomic response in females over microevolutionary timescales to uncover the extent to which post-insemination reproductive traits share a genetic basis between the sexes. We find that differential gene expression is driven by female ancestral or evolved generation alone and that male generation has no impact on changes in gene expression. Almost all differentially expressed genes were downregulated in evolved females. Moreover, 80% of these gene were located on the X chromosome and have wildtype female-biased expression profiles. Changes in gene expression profiles were likely driven through trans -acting pathways that are shared between the sexes. We found no evidence that the core dosage compensation machinery was impacted by experimental evolution. Together these data suggest masculinization of the female transcriptome driven by direct selection on male sperm competitive ability. Our results indicate that on short evolutionary timescales sexual selection can generate sexual conflict in expression space.

LAY SUMMARY: Sexual selection drives the evolution of some of the most dramatic phenotypic differences between the sexes. Such sexual dimorphism is so common across multicellular organisms that we often overlook how remarkable it is for shared genetic material to create numerous and complex sex differences. At an evolutionary level, sexual dimorphism furthers the opportunity for sex-specific selection to optimize the fitness of a given sex. As a consequence, sex-specific selection, such as sexual selection, can have an indirect evolutionary response in the other sex due to genetic associations created by the sexes sharing the same genome. This correlated evolutionary response can create sexual conflict by shifting a sex away from their fitness optimum. At the functional level, sexual dimorphism is generated is through sex-specific regulation of gene expression. Bridging the evolutionary response to sexual selection with the evolution of sex-specific gene regulation during post-mating interactions has proved challenging. We previously used experimental evolution to increase male fertility by directly selecting for increased sperm competitive ability. In this study, we examined the effect of this direct selection on males on gene expression patterns in females. Differential gene expression was determined by whether a female was ancestral or evolved generation, indicating that gene expression changes were an evolved response due to indirect selection on females. Significantly differentially expressed genes were downregulated in evolved females. These genes tended to be female-biased in wildtype individuals and located on the X chromosome. The downregulation of X-linked genes suggests expression levels in females equal to or lower than that in males. Together these results indicate a less female-like transcriptome after experimental evolution. This supports a sexual conflict scenario by which direct sexual selection on males indirectly masculinizes the female transcriptome over short evolutionary timescales.}, } @article {pmid37337232, year = {2023}, author = {Sarkar, MMH and Rahman, MS and Islam, MR and Rahman, A and Islam, MS and Banu, TA and Akter, S and Goswami, B and Jahan, I and Habib, MA and Uddin, MM and Mia, MZ and Miah, MI and Shaikh, AA and Khan, MS}, title = {Comparative phylogenetic analysis and transcriptomic profiling of Dengue (DENV-3 genotype I) outbreak in 2021 in Bangladesh.}, journal = {Virology journal}, volume = {20}, number = {1}, pages = {127}, pmid = {37337232}, issn = {1743-422X}, mesh = {Humans ; Phylogeny ; Bangladesh/epidemiology ; *Transcriptome ; *Dengue/epidemiology ; Disease Outbreaks ; Genotype ; Serogroup ; }, abstract = {BACKGROUND: The next-generation sequencing (NGS) technology facilitates in-depth study of host-pathogen metatranscriptome. We, therefore, implicated phylodynamic and transcriptomic approaches through NGS technology to know/understand the dengue virus (DENV) origin and host response with dengue fever.

METHODS: In this study, blood serum RNA was extracted from 21 dengue patients and 3 healthy individuals. Total transcriptomic data were analyzed for phylogenetic, phylodynamic, differential express gene (DEG), and gene ontology (GO) using respective bioinformatics tools.

RESULTS: The viral genome sequence revealed dengue viral genome size ranges 10647 to 10707 nucleotide. Phylogenetic and phylodynamic analysis showed that the 2021 epidemic isolates were DENV-3 genotype-I and maintained as a new clade in compared to 2019 epidemic. Transcriptome analysis showed a total of 2686 genes were DEG in dengue patients compared to control with a q-value < 0.05. DESeq2 plot counts function of the top 24 genes with the smallest q-values of differential gene expression of RNA-seq data showed that 11 genes were upregulated, whereas 13 genes were downregulated. GO analysis showed a significant upregulation (p = < 0.001) in a process of multicellular organismal, nervous system, sensory perception of chemical stimulus, and G protein-coupled receptor signaling pathways in the dengue patients. However, there were a significant downregulation (p = < 0.001) of intracellular component, cellular anatomical entity, and protein-containing complex in dengue patients. Most importantly, there was a significant increase of a class of immunoregulatory proteins in dengue patients in compared to the controls, with increased GO of immune system process. In addition, upregulation of toll receptor (TLR) signaling pathways were found in dengue patients. These TLR pathways were particularly involved for the activation of innate system coupled with adaptive immune system that probably involved the rapid elimination of dengue virus infected cells. These differentially expressed genes could be further investigated for target based prophylactic interventions for dengue.

CONCLUSION: This is a first report describing DENV complete genomic features and differentially expressed genes in patients in Bangladesh. These genes may have diagnostic and therapeutic values for dengue infection. Continual genomic surveillance is required to further investigate the shift in dominant genotypes in relation to viral pathogenesis.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12985-023-02030-1.}, } @article {pmid37592065, year = {2023}, author = {Shen, J and Paterson, GA and Wang, Y and Kirschvink, JL and Pan, Y and Lin, W}, title = {Renaissance for magnetotactic bacteria in astrobiology.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, pmid = {37592065}, issn = {1751-7370}, support = {T2225011//National Natural Science Foundation of China (National Science Foundation of China)/ ; 42293293//National Natural Science Foundation of China (National Science Foundation of China)/ ; 42202339//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2023M733478//China Postdoctoral Science Foundation/ ; NE/P017266/1//RCUK | Natural Environment Research Council (NERC)/ ; }, abstract = {Capable of forming magnetofossils similar to some magnetite nanocrystals observed in the Martian meteorite ALH84001, magnetotactic bacteria (MTB) once occupied a special position in the field of astrobiology during the 1990s and 2000s. This flourish of interest in putative Martian magnetofossils faded from all but the experts studying magnetosome formation, based on claims that abiotic processes could produce magnetosome-like magnetite crystals. Recently, the rapid growth in our knowledge of the extreme environments in which MTB thrive and their phylogenic heritage, leads us to advocate for a renaissance of MTB in astrobiology. In recent decades, magnetotactic members have been discovered alive in natural extreme environments with wide ranges of salinity (up to 90 g L[-1]), pH (1-10), and temperature (0-70 °C). Additionally, some MTB populations are found to be able to survive irradiated, desiccated, metal-rich, hypomagnetic, or microgravity conditions, and are capable of utilizing simple inorganic compounds such as sulfate and nitrate. Moreover, MTB likely emerged quite early in Earth's history, coinciding with a period when the Martian surface was covered with liquid water as well as a strong magnetic field. MTB are commonly discovered in suboxic or oxic-anoxic interfaces in aquatic environments or sediments similar to ancient crater lakes on Mars, such as Gale crater and Jezero crater. Taken together, MTB can be exemplary model microorganisms in astrobiology research, and putative ancient Martian life, if it ever occurred, could plausibly have included magnetotactic microorganisms. Furthermore, we summarize multiple typical biosignatures that can be applied for the detection of ancient MTB on Earth and extraterrestrial MTB-like life. We suggest transporting MTB to space stations and simulation chambers to further investigate their tolerance potential and distinctive biosignatures to aid in understanding the evolutionary history of MTB and the potential of magnetofossils as an extraterrestrial biomarker.}, } @article {pmid37588220, year = {2024}, author = {Luo, H and Birjandi, AA and Ren, F and Sun, T and Sharpe, PT and Sun, H and An, Z}, title = {Advances in oral mesenchymal stem cell-derived extracellular vesicles in health and disease.}, journal = {Genes & diseases}, volume = {11}, number = {1}, pages = {346-357}, pmid = {37588220}, issn = {2352-3042}, abstract = {Extracellular vesicles (EVs) are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicellular organisms. EVs contain nucleic acids, proteins, lipids, and other cellular components, regulating many basic biological processes and playing an important role in regenerative medicine and diseases. EVs can be traced to their cells of origin and exhibit a similar function. Moreover, EVs demonstrate low immunogenicity, good biocompatibility, and fewer side effects, compared to their parent cells. Mesenchymal stem cells (MSCs) are one of the most important resource cells for EVs, with a great capacity for self-renewal and multipotent differentiation, and play an essential role in stem cell therapy. The mechanism of MSC therapy was thought to be attributed to the differentiation of MSCs after targeted migration, as previously noted. However, emerging evidence shows the previously unknown role of MSC-derived paracrine factors in stem cell therapy. Especially EVs derived from oral tissue MSCs (OMSC-EVs), show more advantages than those of all other MSCs in tissue repair and regeneration, due to their lower invasiveness and easier accessibility for sample collection. Here, we systematically review the biogenesis and biological characteristics of OMSC-EVs, as well as the role of OMSC-EVs in intercellular communication. Furthermore, we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic diseases. We highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical translation. We aim to provide valuable insights for the explorative clinical application of OMSC-EVs.}, } @article {pmid37586948, year = {2023}, author = {Shalev, O and Ye, X and Ratzke, C}, title = {Replaying the evolution of multicellularity.}, journal = {Trends in ecology & evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tree.2023.07.007}, pmid = {37586948}, issn = {1872-8383}, abstract = {The first organisms on Earth were presumably unicellular. At one point, evolution shaped these individual cells into multicellular organisms, which was a significant transition in the history of life on Earth. To investigate how this change happened, Bozdag et al. re-ran evolution in the lab and observed how single-celled yeast forms large multicellular aggregates.}, } @article {pmid37565532, year = {2023}, author = {Cervantes, S and Kesälahti, R and Kumpula, TA and Mattila, TM and Helanterä, H and Pyhäjärvi, T}, title = {Strong purifying selection in haploid tissue-specific genes of Scots pine supports the masking theory.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msad183}, pmid = {37565532}, issn = {1537-1719}, abstract = {The masking theory states that genes expressed in haploid stage will be under more efficient selection. In contrast, selection will be less efficient in genes expressed in diploid stage, where the fitness effects of recessive deleterious or beneficial mutations can be hidden from selection in heterozygous form. This difference can influence several evolutionary processes such as the maintenance of genetic variation, adaptation rate, and genetic load. Masking theory expectations have been confirmed in single-cell haploid and diploid organisms. However, in multicellular organisms, such as plants, the effects of haploid selection are not clear-cut. In plants, the great majority of studies indicating haploid selection have been carried out using male haploid tissues in angiosperms. Hence, evidence in these systems is confounded with the effects of sexual selection and intra-specific competition. Evidence from other plant groups is scarce and results show no support for the masking theory. Here we have used a gymnosperm Scots pine megagametophyte, a maternally-derived seed haploid tissue, and four diploid tissues to test the strength of purifying selection on a set of genes with tissue-specific expression. By using targeted resequencing data of those genes, we obtained estimates of genetic diversity, the site frequency spectrum of 0-fold and 4-fold sites, and inferred the distribution of fitness effects (DFE) of new mutations in haploid and diploid tissue-specific genes. Our results show that purifying selection is stronger for tissue-specific genes expressed in the haploid megagametophyte tissue, and that this signal of strong selection is not an artifact driven by high expression levels.}, } @article {pmid37563336, year = {2023}, author = {Mocarski, ES}, title = {Programmed Necrosis in Host Defense.}, journal = {Current topics in microbiology and immunology}, volume = {}, number = {}, pages = {}, doi = {10.1007/82_2023_264}, pmid = {37563336}, issn = {0070-217X}, abstract = {Host control over infectious disease relies on the ability of cells in multicellular organisms to detect and defend against pathogens to prevent disease. Evolution affords mammals with a wide variety of independent immune mechanisms to control or eliminate invading infectious agents. Many pathogens acquire functions to deflect these immune mechanisms and promote infection. Following successful invasion of a host, cell autonomous signaling pathways drive the production of inflammatory cytokines, deployment of restriction factors and induction of cell death. Combined, these innate immune mechanisms attract dendritic cells, neutrophils and macrophages as well as innate lymphoid cells such as natural killer cells that all help control infection. Eventually, the development of adaptive pathogen-specific immunity clears infection and provides immune memory of the encounter. For obligate intracellular pathogens such as viruses, diverse cell death pathways make a pivotal contribution to early control by eliminating host cells before progeny are produced. Pro-apoptotic caspase-8 activity (along with caspase-10 in humans) executes extrinsic apoptosis, a nonlytic form of cell death triggered by TNF family death receptors (DRs). Over the past two decades, alternate extrinsic apoptosis and necroptosis outcomes have been described. Programmed necrosis, or necroptosis, occurs when receptor interacting protein kinase 3 (RIPK3) activates mixed lineage kinase-like (MLKL), causing cell leakage. Thus, activation of DRs, toll-like receptors (TLRs) or pathogen sensor Z-nucleic acid binding protein 1 (ZBP1) initiates apoptosis as well as necroptosis if not blocked by virus-encoded inhibitors. Mammalian cell death pathways are blocked by herpesvirus- and poxvirus-encoded cell death suppressors. Growing evidence has revealed the importance of Z-nucleic acid sensor, ZBP1, in the cell autonomous recognition of both DNA and RNA virus infection. This volume will explore the detente between viruses and cells to manage death machinery and avoid elimination to support dissemination within the host animal.}, } @article {pmid37559824, year = {2023}, author = {Golenberg, EM and Popadić, A and Hao, W}, title = {Transcriptome analyses of leaf architecture in Sansevieria support a common genetic toolkit in the parallel evolution of unifacial leaves in monocots.}, journal = {Plant direct}, volume = {7}, number = {8}, pages = {e511}, pmid = {37559824}, issn = {2475-4455}, abstract = {Planar structures dramatically increase the surface-area-to-volume ratio, which is critically important for multicellular organisms. In this study, we utilize naturally occurring phenotypic variation among three Sansivieria species (Asperagaceae) to investigate leaf margin expression patterns that are associated with mediolateral and adaxial/abaxial development. We identified differentially expressed genes (DEGs) between center and margin leaf tissues in two planar-leaf species Sansevieria subspicata and Sansevieria trifasciata and compared these with expression patterns within the cylindrically leaved Sansevieria cylindrica. Two YABBY family genes, homologs of FILAMENTOUS FLOWER and DROOPING LEAF, are overexpressed in the center leaf tissue in the planar-leaf species and in the tissue of the cylindrical leaves. As mesophyll structure does not indicate adaxial versus abaxial differentiation, increased leaf thickness results in more water-storage tissue and enhances resistance to aridity. This suggests that the cylindrical-leaf in S. cylindrica is analogous to the central leaf tissue in the planar-leaf species. Furthermore, the congruence of the expression patterns of these YABBY genes in Sansevieria with expression patterns found in other unifacial monocot species suggests that patterns of parallel evolution may be the result of similar solutions derived from a limited developmental toolbox.}, } @article {pmid37556606, year = {2023}, author = {Majic, P and Payne, JL}, title = {Developmental selection and the perception of mutation bias.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msad179}, pmid = {37556606}, issn = {1537-1719}, abstract = {The notion that mutations are random relative to their fitness effects is central to the Neo-Darwinian view of evolution. However, a recent interpretation of the patterns of mutation accumulation in the genome of Arabidopsis thaliana has challenged this notion, arguing for the presence of a targeted DNA repair mechanism that causes a non-random association of mutation rates and fitness effects. Specifically, this mechanism was suggested to cause a reduction in the rates of mutations on essential genes, thus lowering the rates of deleterious mutations. Central to this argument were attempts to rule out selection at the population level. Here, we offer an alternative and parsimonious interpretation of the patterns of mutation accumulation previously attributed to mutation bias, showing how they can instead or additionally be caused by developmental selection, i.e., selection occurring at the cellular level during the development of a multicellular organism. Thus, the depletion of deleterious mutations in A. thaliana may indeed be the result of a selective process, rather than a bias in mutation. More broadly, our work highlights the importance of considering development in the interpretation of population genetic analyses of multicellular organisms, and it emphasizes that efforts to identify mechanisms involved in mutational biases should explicitly account for developmental selection.}, } @article {pmid37551449, year = {2023}, author = {Khan, AK and Muñoz-Castro, G and Muñoz, JJ}, title = {Single and two-cells shape analysis from energy functionals for three-dimensional vertex models.}, journal = {International journal for numerical methods in biomedical engineering}, volume = {}, number = {}, pages = {e3766}, doi = {10.1002/cnm.3766}, pmid = {37551449}, issn = {2040-7947}, support = {//Generalitat de Catalunya/ ; //Ministerio de Ciencia e Innovación/ ; //Ministry of Federal Education and Professional Training/ ; //Higher Education Commission (under the Ministry of Federal Education and Professional Training) of Pakistan/ ; CEX2018-000797-S//Spanish Ministry of Science and Innovation/ ; PID2020-116141GB-I00//Spanish Ministry of Science and Innovation/ ; 2021 SGR 01049//Catalan government Generalitat de Catalunya/ ; }, abstract = {Vertex models have been extensively used for simulating the evolution of multicellular systems, and have given rise to important global properties concerning their macroscopic rheology or jamming transitions. These models are based on the definition of an energy functional, which fully determines the cellular response and conclusions. While two-dimensional vertex models have been widely employed, three-dimensional models are far more scarce, mainly due to the large amount of configurations that they may adopt and the complex geometrical transitions they undergo. We here investigate the shape of single and two-cells configurations as a function of the energy terms, and we study the dependence of the final shape on the model parameters: namely the exponent of the term penalising cell-cell adhesion and surface contractility. In single cell analysis, we deduce analytically the radius and limit values of the contractility for linear and quadratic surface energy terms, in 2D and 3D. In two-cells systems, symmetrical and asymmetrical, we deduce the evolution of the aspect ratio and the relative radius. While in functionals with linear surface terms yield the same aspect ratio in 2D and 3D, the configurations when using quadratic surface terms are distinct. We relate our results with well-known solutions from capillarity theory, and verify our analytical findings with a three-dimensional vertex model.}, } @article {pmid37546755, year = {2023}, author = {Phillips, JE and Pan, D}, title = {The Hippo kinase cascade regulates a contractile cell behavior and cell density in a close unicellular relative of animals.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.07.25.550562}, pmid = {37546755}, abstract = {The genomes of close unicellular relatives of animals encode orthologs of many genes that regulate animal development. However, little is known about the function of such genes in unicellular organisms or the evolutionary process by which these genes came to function in multicellular development. The Hippo pathway, which regulates cell proliferation and tissue size in animals, is present in some of the closest unicellular relatives of animals, including the amoeboid organism Capsaspora owczarzaki . We previously showed that the Capsaspora ortholog of the Hippo pathway nuclear effector Yorkie/YAP/TAZ (coYki) regulates actin dynamics and the three-dimensional morphology of Capsaspora cell aggregates, but is dispensable for cell proliferation control (Phillips et al., 2022). However, the function of upstream Hippo pathway components, and whether and how they regulate coYki in Capsaspora , remained unknown. Here, we analyze the function of the upstream Hippo pathway kinases coHpo and coWts in Capsaspora by generating mutant lines for each gene. Loss of either kinase results in increased nuclear localization of coYki, indicating an ancient, premetazoan origin of this Hippo pathway regulatory mechanism. Strikingly, we find that loss of either kinase causes a contractile cell behavior and increased density of cell packing within Capsaspora aggregates. We further show that this increased cell density is not due to differences in proliferation, but rather actomyosin-dependent changes in the multicellular architecture of aggregates. Given its well-established role in cell density-regulated proliferation in animals, the increased density of cell packing in coHpo and coWts mutants suggests a shared and possibly ancient and conserved function of the Hippo pathway in cell density control. Together, these results implicate cytoskeletal regulation but not proliferation as an ancestral function of the Hippo pathway and uncover a novel role for Hippo signaling in regulating cell density in a proliferation-independent manner.}, } @article {pmid37540742, year = {2023}, author = {Sartor, F and Xu, X and Popp, T and Dodd, AN and Kovács, ÁT and Merrow, M}, title = {The circadian clock of the bacterium B. subtilis evokes properties of complex, multicellular circadian systems.}, journal = {Science advances}, volume = {9}, number = {31}, pages = {eadh1308}, pmid = {37540742}, issn = {2375-2548}, mesh = {*Circadian Clocks ; Bacillus subtilis ; Circadian Rhythm ; Light ; Eukaryota ; }, abstract = {Circadian clocks are pervasive throughout nature, yet only recently has this adaptive regulatory program been described in nonphotosynthetic bacteria. Here, we describe an inherent complexity in the Bacillus subtilis circadian clock. We find that B. subtilis entrains to blue and red light and that circadian entrainment is separable from masking through fluence titration and frequency demultiplication protocols. We identify circadian rhythmicity in constant light, consistent with the Aschoff's rule, and entrainment aftereffects, both of which are properties described for eukaryotic circadian clocks. We report that circadian rhythms occur in wild isolates of this prokaryote, thus establishing them as a general property of this species, and that its circadian system responds to the environment in a complex fashion that is consistent with multicellular eukaryotic circadian systems.}, } @article {pmid37511419, year = {2023}, author = {Erenpreisa, J and Vainshelbaum, NM and Lazovska, M and Karklins, R and Salmina, K and Zayakin, P and Rumnieks, F and Inashkina, I and Pjanova, D and Erenpreiss, J}, title = {The Price of Human Evolution: Cancer-Testis Antigens, the Decline in Male Fertility and the Increase in Cancer.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511419}, issn = {1422-0067}, mesh = {Pregnancy ; Animals ; Humans ; Male ; Female ; *Testis/metabolism ; Placenta ; Spermatogenesis/genetics ; Reproduction ; *Neoplasms/genetics/metabolism ; Mammals ; Polyploidy ; Fertility/genetics ; }, abstract = {The increasing frequency of general and particularly male cancer coupled with the reduction in male fertility seen worldwide motivated us to seek a potential evolutionary link between these two phenomena, concerning the reproductive transcriptional modules observed in cancer and the expression of cancer-testis antigens (CTA). The phylostratigraphy analysis of the human genome allowed us to link the early evolutionary origin of cancer via the reproductive life cycles of the unicellulars and early multicellulars, potentially driving soma-germ transition, female meiosis, and the parthenogenesis of polyploid giant cancer cells (PGCCs), with the expansion of the CTA multi-families, very late during their evolution. CTA adaptation was aided by retrovirus domestication in the unstable genomes of mammals, for protecting male fertility in stress conditions, particularly that of humans, as compensation for the energy consumption of a large complex brain which also exploited retrotransposition. We found that the early and late evolutionary branches of human cancer are united by the immunity-proto-placental network, which evolved in the Cambrian and shares stress regulators with the finely-tuned sex determination system. We further propose that social stress and endocrine disruption caused by environmental pollution with organic materials, which alter sex determination in male foetuses and further spermatogenesis in adults, bias the development of PGCC-parthenogenetic cancer by default.}, } @article {pmid37498572, year = {2023}, author = {Ma, X and Shi, X and Wang, Q and Zhao, M and Zhang, Z and Zhong, B}, title = {A reinvestigation of multiple independent evolution and Triassic-Jurassic origin of multicellular Volvocine algae.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evad142}, pmid = {37498572}, issn = {1759-6653}, abstract = {The evolution of multicellular organisms is considered to be a major evolutionary transition, profoundly affecting the ecology and evolution of nearly all life on earth. The volvocine algae, a unique clade of chlorophytes with diverse cell morphology, provide an appealing model for investigating the evolution of multicellularity and development. However, the phylogenetic relationship and timescale of the volvocine algae are not fully resolved. Here, we use extensive taxon and gene sampling to reconstruct the phylogeny of the volvocine algae. Our results support that the colonial volvocine algae are not monophyletic group, and multicellularity independently evolve at least twice in the volvocine algae, once in Tetrabaenaceae and another in the Goniaceae + Volvocaceae. The simulation analyses suggest that incomplete lineage sorting is a major factor for the tree topology discrepancy, which imply that the multispecies coalescent model better fits the data used in this study. The coalescent-based species tree supports that the Goniaceae is monophyletic, and Crucicarteria is the earliest diverging lineage, followed by Hafniomonas and Radicarteria within the Volvocales. By considering the multiple uncertainties in divergence time estimation, the dating analyses indicate that the volvocine algae occurred during the Cryogenian to Ediacaran (696.6-551.1 Ma), and multicellularity in the volvocine algae originated from the Triassic to Jurassic. Our phylogeny and timeline provide an evolutionary framework for studying the evolution of key traits and the origin of multicellularity in the volvocine algae.}, } @article {pmid37494396, year = {2023}, author = {Fichman, Y and Rowland, L and Oliver, MJ and Mittler, R}, title = {ROS are evolutionary conserved cell-to-cell stress signals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {31}, pages = {e2305496120}, pmid = {37494396}, issn = {1091-6490}, support = {R01 GM111364/GM/NIGMS NIH HHS/United States ; GM111364/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Reactive Oxygen Species ; *Hydrogen Peroxide ; *Signal Transduction ; Cell Communication ; Plants ; Mammals ; }, abstract = {Cell-to-cell communication is fundamental to multicellular organisms and unicellular organisms living in a microbiome. It is thought to have evolved as a stress- or quorum-sensing mechanism in unicellular organisms. A unique cell-to-cell communication mechanism that uses reactive oxygen species (ROS) as a signal (termed the "ROS wave") was identified in flowering plants. This process is essential for systemic signaling and plant acclimation to stress and can spread from a small group of cells to the entire plant within minutes. Whether a similar signaling process is found in other organisms is however unknown. Here, we report that the ROS wave can be found in unicellular algae, amoeba, ferns, mosses, mammalian cells, and isolated hearts. We further show that this process can be triggered in unicellular and multicellular organisms by a local stress or H2O2 treatment and blocked by the application of catalase or NADPH oxidase inhibitors and that in unicellular algae it communicates important stress-response signals between cells. Taken together, our findings suggest that an active process of cell-to-cell ROS signaling, like the ROS wave, evolved before unicellular and multicellular organisms diverged. This mechanism could have communicated an environmental stress signal between cells and coordinated the acclimation response of many different cells living in a community. The finding of a signaling process, like the ROS wave, in mammalian cells further contributes to our understanding of different diseases and could impact the development of drugs that target for example cancer or heart disease.}, } @article {pmid37492150, year = {2023}, author = {Capp, JP and Thomas, F and Marusyk, A and M Dujon, A and Tissot, S and Gatenby, R and Roche, B and Ujvari, B and DeGregori, J and Brown, JS and Nedelcu, AM}, title = {The paradox of cooperation among selfish cancer cells.}, journal = {Evolutionary applications}, volume = {16}, number = {7}, pages = {1239-1256}, pmid = {37492150}, issn = {1752-4571}, abstract = {It is traditionally assumed that during cancer development, tumor cells abort their initially cooperative behavior (i.e., cheat) in favor of evolutionary strategies designed solely to enhance their own fitness (i.e., a "selfish" life style) at the expense of that of the multicellular organism. However, the growth and progress of solid tumors can also involve cooperation among these presumed selfish cells (which, by definition, should be noncooperative) and with stromal cells. The ultimate and proximate reasons behind this paradox are not fully understood. Here, in the light of current theories on the evolution of cooperation, we discuss the possible evolutionary mechanisms that could explain the apparent cooperative behaviors among selfish malignant cells. In addition to the most classical explanations for cooperation in cancer and in general (by-product mutualism, kin selection, direct reciprocity, indirect reciprocity, network reciprocity, group selection), we propose the idea that "greenbeard" effects are relevant to explaining some cooperative behaviors in cancer. Also, we discuss the possibility that malignant cooperative cells express or co-opt cooperative traits normally expressed by healthy cells. We provide examples where considerations of these processes could help understand tumorigenesis and metastasis and argue that this framework provides novel insights into cancer biology and potential strategies for cancer prevention and treatment.}, } @article {pmid37481773, year = {2023}, author = {Evans, JA and Schwartz, WJ}, title = {On the origin and evolution of the dual oscillator model underlying the photoperiodic clockwork in the suprachiasmatic nucleus.}, journal = {Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology}, volume = {}, number = {}, pages = {}, pmid = {37481773}, issn = {1432-1351}, support = {R01GM143545/NH/NIH HHS/United States ; }, abstract = {Decades have now passed since Colin Pittendrigh first proposed a model of a circadian clock composed of two coupled oscillators, individually responsive to the rising and setting sun, as a flexible solution to the challenge of behavioral and physiological adaptation to the changing seasons. The elegance and predictive power of this postulation has stimulated laboratories around the world in searches to identify and localize such hypothesized evening and morning oscillators, or sets of oscillators, in insects, rodents, and humans, with experimental designs and approaches keeping pace over the years with technological advances in biology and neuroscience. Here, we recount the conceptual origin and highlight the subsequent evolution of this dual oscillator model for the circadian clock in the mammalian suprachiasmatic nucleus; and how, despite our increasingly sophisticated view of this multicellular pacemaker, Pittendrigh's binary conception has remained influential in our clock models and metaphors.}, } @article {pmid37481138, year = {2023}, author = {Corallo, D and Dalla Vecchia, M and Lazic, D and Taschner-Mandl, S and Biffi, A and Aveic, S}, title = {The molecular basis of tumor metastasis and current approaches to decode targeted migration-promoting events in pediatric neuroblastoma.}, journal = {Biochemical pharmacology}, volume = {215}, number = {}, pages = {115696}, doi = {10.1016/j.bcp.2023.115696}, pmid = {37481138}, issn = {1873-2968}, abstract = {Cell motility is a crucial biological process that plays a critical role in the development of multicellular organisms and is essential for tissue formation and regeneration. However, uncontrolled cell motility can lead to the development of various diseases, including neoplasms. In this review, we discuss recent advances in the discovery of regulatory mechanisms underlying the metastatic spread of neuroblastoma, a solid pediatric tumor that originates in the embryonic migratory cells of the neural crest. The highly motile phenotype of metastatic neuroblastoma cells requires targeting of intracellular and extracellular processes, that, if affected, would be helpful for the treatment of high-risk patients with neuroblastoma, for whom current therapies remain inadequate. Development of new potentially migration-inhibiting compounds and standardized preclinical approaches for the selection of anti-metastatic drugs in neuroblastoma will also be discussed.}, } @article {pmid37475643, year = {2023}, author = {Kato, D and Aoyama, Y and Nishida, K and Takahashi, Y and Sakamoto, T and Takeda, I and Tatematsu, T and Go, S and Saito, Y and Kunishima, S and Cheng, J and Hou, L and Tachibana, Y and Sugio, S and Kondo, R and Eto, F and Sato, S and Moorhouse, AJ and Yao, I and Kadomatsu, K and Setou, M and Wake, H}, title = {Regulation of lipid synthesis in myelin modulates neural activity and is required for motor learning.}, journal = {Glia}, volume = {}, number = {}, pages = {}, doi = {10.1002/glia.24441}, pmid = {37475643}, issn = {1098-1136}, support = {JPMJCR1755//Core Research for Evolutional Science and Technology/ ; JPMJCR22P6//Core Research for Evolutional Science and Technology/ ; 20H05699//Grants-in-Aid for Transformative Research Areas (A)/ ; 21H05587//Grants-in-Aid for Transformative Research Areas (A)/ ; JP23gm1410011 h0002//Japan Agency for Medical Research and Development/ ; JP22ak0101150//Japan Agency for Medical Research and Development/ ; 26710004//Grants-in-Aid for Young Scientists (A)/ ; JPMJFR2145//FOREST program/ ; 20K16574//Grants-in-Aid for Young Scientists/ ; //Nagoya University CIBoG WISE program from MEXT/ ; 25110732//Grants-in-Aid for Scientific Research on Innovative Areas/ ; 19H05219//Grants-in-Aid for Scientific Research on Innovative Areas/ ; 19H04753//Grants-in-Aid for Scientific Research on Innovative Areas/ ; 20KK0170//Fostering Joint International Research (B)/ ; 21H02662//Grants-in-Aid for Scientific Research (B)/ ; 18H02598//Grants-in-Aid for Scientific Research (B)/ ; }, abstract = {Brain function relies on both rapid electrical communication in neural circuitry and appropriate patterns or synchrony of neural activity. Rapid communication between neurons is facilitated by wrapping nerve axons with insulation by a myelin sheath composed largely of different lipids. Recent evidence has indicated that the extent of myelination of nerve axons can adapt based on neural activity levels and this adaptive myelination is associated with improved learning of motor tasks, suggesting such plasticity may enhance effective learning. In this study, we examined whether another aspect of myelin plasticity-changes in myelin lipid synthesis and composition-may also be associated with motor learning. We combined a motor learning task in mice with in vivo two-photon imaging of neural activity in the primary motor cortex (M1) to distinguish early and late stages of learning and then probed levels of some key myelin lipids using mass spectrometry analysis. Sphingomyelin levels were elevated in the early stage of motor learning while galactosylceramide levels were elevated in the middle and late stages of motor learning, and these changes were correlated across individual mice with both learning performance and neural activity changes. Targeted inhibition of oligodendrocyte-specific galactosyltransferase expression, the enzyme that synthesizes myelin galactosylceramide, impaired motor learning. Our results suggest regulation of myelin lipid composition could be a novel facet of myelin adaptations associated with learning.}, } @article {pmid37468829, year = {2023}, author = {Vroomans, RMA and Colizzi, ES}, title = {Evolution of selfish multicellularity: collective organisation of individual spatio-temporal regulatory strategies.}, journal = {BMC ecology and evolution}, volume = {23}, number = {1}, pages = {35}, pmid = {37468829}, issn = {2730-7182}, mesh = {Animals ; *Biological Evolution ; *Reproduction ; Cell Differentiation ; }, abstract = {BACKGROUND: The unicellular ancestors of modern-day multicellular organisms were remarkably complex. They had an extensive set of regulatory and signalling genes, an intricate life cycle and could change their behaviour in response to environmental changes. At the transition to multicellularity, some of these behaviours were co-opted to organise the development of the nascent multicellular organism. Here, we focus on the transition to multicellularity before the evolution of stable cell differentiation, to reveal how the emergence of clusters affects the evolution of cell behaviour.

RESULTS: We construct a computational model of a population of cells that can evolve the regulation of their behavioural state - either division or migration - and study both a unicellular and a multicellular context. Cells compete for reproduction and for resources to survive in a seasonally changing environment. We find that the evolution of multicellularity strongly determines the co-evolution of cell behaviour, by altering the competition dynamics between cells. When adhesion cannot evolve, cells compete for survival by rapidly migrating towards resources before dividing. When adhesion evolves, emergent collective migration alleviates the pressure on individual cells to reach resources. This allows individual cells to maximise their own replication. Migrating adhesive clusters display striking patterns of spatio-temporal cell state changes that visually resemble animal development.

CONCLUSIONS: Our model demonstrates how emergent selection pressures at the onset of multicellularity can drive the evolution of cellular behaviour to give rise to developmental patterns.}, } @article {pmid37465696, year = {2023}, author = {Narayanan, SA}, title = {Gravity's effect on biology.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1199175}, pmid = {37465696}, issn = {1664-042X}, abstract = {Gravity is a fundamental interaction that permeates throughout our Universe. On Earth, gravity gives weight to physical objects, and has been a constant presence throughout terrestrial biological evolution. Thus, gravity has shaped all biological functions, some examples include the growth of plants (e.g., gravitropism), the structure and morphology of biological parts in multicellular organisms, to its effects on our physiological function when humans travel into space. Moreover, from an evolutionary perspective, gravity has been a constant force on biology, and life, to our understanding, should have no reason to not experience the effects of gravity. Interestingly, there appear to be specific biological mechanisms that activate in the absence of gravity, with the space environment the only location to study the effects of a lack of gravity on biological systems. Thus, in this perspective piece, biological adaptations from the cellular to the whole organism levels to the presence and absence of gravity will be organized and described, as well as outlining future areas of research for gravitational biological investigations to address. Up to now, we have observed and shown how gravity effects biology at different levels, with a few examples including genetic (e.g., cell cycle, metabolism, signal transduction associated pathways, etc.), biochemically (e.g., cytoskeleton, NADPH oxidase, Yes-associated protein, etc.), and functionally (e.g., astronauts experiencing musculoskeletal and cardiovascular deconditioning, immune dysfunction, etc., when traveling into space). Based from these observations, there appear to be gravity-sensitive and specific pathways across biological organisms, though knowledge gaps of the effects of gravity on biology remain, such as similarities and differences across species, reproduction, development, and evolutionary adaptations, sex-differences, etc. Thus, here an overview of the literature is provided for context of gravitational biology research to-date and consideration for future studies, as we prepare for long-term occupation of low-Earth Orbit and cis-Lunar space, and missions to the Moon and Mars, experiencing the effects of Lunar and Martian gravity on biology, respectively, through our Artemis program.}, } @article {pmid37461608, year = {2023}, author = {Compton, Z and Harris, V and Mellon, W and Rupp, S and Mallo, D and Kapsetaki, S and Wilmot, M and Kennington, R and Noble, K and Baciu, C and Ramirez, L and Peraza, A and Martins, B and Sudhakar, S and Aksoy, S and Furukawa, G and Vincze, O and Giraudeau, M and Duke, E and Spiro, S and Flach, E and Davidson, H and Zehnder, A and Graham, T and Troan, B and Harrison, T and Tollis, M and Schiffman, J and Aktipis, A and Abegglen, L and Maley, C and Boddy, A}, title = {Cancer Prevalence Across Vertebrates.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37461608}, abstract = {Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Peto's Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer.}, } @article {pmid37459530, year = {2023}, author = {Xu, H and Nejad, MR and Yeomans, JM and Wu, Y}, title = {Geometrical control of interface patterning underlies active matter invasion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {30}, pages = {e2219708120}, pmid = {37459530}, issn = {1091-6490}, mesh = {*Bacteria ; }, abstract = {Interaction between active materials and the boundaries of geometrical confinement is key to many emergent phenomena in active systems. For living active matter consisting of animal cells or motile bacteria, the confinement boundary is often a deformable interface, and it has been unclear how activity-induced interface dynamics might lead to morphogenesis and pattern formation. Here, we studied the evolution of bacterial active matter confined by a deformable boundary. We found that an ordered morphological pattern emerged at the interface characterized by periodically spaced interfacial protrusions; behind the interfacial protrusions, bacterial swimmers self-organized into multicellular clusters displaying +1/2 nematic defects. Subsequently, a hierarchical sequence of transitions from interfacial protrusions to creeping branches allowed the bacterial active drop to rapidly invade surrounding space with a striking self-similar branch pattern. We found that this interface patterning is geometrically controlled by the local curvature of the interface, a phenomenon we denote as collective curvature sensing. Using a continuum active model, we revealed that the collective curvature sensing arises from enhanced active stresses near high-curvature regions, with the active length scale setting the characteristic distance between the interfacial protrusions. Our findings reveal a protrusion-to-branch transition as a unique mode of active matter invasion and suggest a strategy to engineer pattern formation of active materials.}, } @article {pmid37445995, year = {2023}, author = {Endres, K and Friedland, K}, title = {Talk to Me-Interplay between Mitochondria and Microbiota in Aging.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37445995}, issn = {1422-0067}, mesh = {*Gastrointestinal Microbiome/physiology ; *Microbiota ; Mitochondria ; Bacteria/metabolism ; }, abstract = {The existence of mitochondria in eukaryotic host cells as a remnant of former microbial organisms has been widely accepted, as has their fundamental role in several diseases and physiological aging. In recent years, it has become clear that the health, aging, and life span of multicellular hosts are also highly dependent on the still-residing microbiota, e.g., those within the intestinal system. Due to the common evolutionary origin of mitochondria and these microbial commensals, it is intriguing to investigate if there might be a crosstalk based on preserved common properties. In the light of rising knowledge on the gut-brain axis, such crosstalk might severely affect brain homeostasis in aging, as neuronal tissue has a high energy demand and low tolerance for according functional decline. In this review, we summarize what is known about the impact of both mitochondria and the microbiome on the host's aging process and what is known about the aging of both entities. For a long time, bacteria were assumed to be immortal; however, recent evidence indicates their aging and similar observations have been made for mitochondria. Finally, we present pathways by which mitochondria are affected by microbiota and give information about therapeutic anti-aging approaches that are based on current knowledge.}, } @article {pmid37441836, year = {2023}, author = {Somers, J and Nelms, B}, title = {The sporophyte-to-gametophyte transition: The haploid generation comes of age.}, journal = {Current opinion in plant biology}, volume = {75}, number = {}, pages = {102416}, doi = {10.1016/j.pbi.2023.102416}, pmid = {37441836}, issn = {1879-0356}, abstract = {Flowering plants alternate between two multicellular generations: the diploid sporophyte and haploid gametophyte. Despite its small size, the gametophyte has significant impacts on plant genetics, evolution, and breeding. Each male pollen grain and female embryo sac is a multicellular organism with independent gene expression, a functioning metabolism, and specialized cell types. In this review, we describe recent progress in understanding the process in which the haploid genome takes over expression from its diploid parent - the sporophyte-to-gametophyte transition. The focus is on pollen, but similar concepts may also apply to the female gametophyte. Technological advances in single-cell genomics offer the opportunity to characterize haploid gene expression in unprecedented detail, positioning the field to make rapid progress.}, } @article {pmid37438660, year = {2023}, author = {Huang, L and Tu, Z and Wei, L and Sun, W and Wang, Y and Bi, S and He, F and Du, L and Chen, J and Kzhyshkowska, J and Wang, H and Chen, D and Zhang, S}, title = {Generating Functional Multicellular Organoids from Human Placenta Villi.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2301565}, doi = {10.1002/advs.202301565}, pmid = {37438660}, issn = {2198-3844}, support = {2022YFC2702501//National Key Research and Development Program of China/ ; 2022YFC2704500//National Key Research and Development Program of China/ ; 81830045//Key Program of National Natural Science Foundation of China/ ; 81071652//National Natural Science Foundation of China/ ; 82171666//National Natural Science Foundation of China/ ; 82201861//National Natural Science Foundation of China/ ; 82271695//National Natural Science Foundation of China/ ; M-0586//Mobility program of Sino German Center/ ; 202201020573//Science and Technology Program of Guangzhou/ ; 2023A03J0378//Science and Technology Program of Guangzhou/ ; 2021B1515120070//China Guangdong Basic and Applied Basic Research Fund/ ; }, abstract = {The interaction between trophoblasts, stroma cells, and immune cells at the maternal-fetal interface constitutes the functional units of the placenta, which is crucial for successful pregnancy outcomes. However, the investigation of this intricate interplay is restricted due to the absence of efficient experimental models. To address this challenge, a robust, reliable methodology for generating placenta villi organoids (PVOs) from early, late, or diseased pregnancies using air-liquid surface culture is developed. PVOs contain cytotrophoblasts that can self-renew and differentiate directly, along with stromal elements that retain native immune cells. Analysis of scRNA sequencing and WES data reveals that PVOs faithfully recapitulate the cellular components and genetic alterations of the corresponding source tissue. Additionally, PVOs derived from patients with preeclampsia exhibit specific pathological features such as inflammation, antiangiogenic imbalance, and decreased syncytin expression. The PVO-based propagation of primary placenta villi should enable a deeper investigation of placenta development and exploration of the underlying pathogenesis and therapeutics of placenta-originated diseases.}, } @article {pmid37436957, year = {2023}, author = {Geng, S and Hamaji, T and Ferris, PJ and Gao, M and Nishimura, Y and Umen, J}, title = {A conserved RWP-RK transcription factor VSR1 controls gametic differentiation in volvocine algae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {29}, pages = {e2305099120}, doi = {10.1073/pnas.2305099120}, pmid = {37436957}, issn = {1091-6490}, support = {R01GM078376/NH/NIH HHS/United States ; }, mesh = {*Seeds ; Sex ; Reproduction ; Germ Cells ; Spermatozoa ; Biotin ; *Chlamydomonas ; }, abstract = {Volvocine green algae are a model for understanding the evolution of mating types and sexes. They are facultatively sexual, with gametic differentiation occurring in response to nitrogen starvation (-N) in most genera and to sex inducer hormone in Volvox. The conserved RWP-RK family transcription factor (TF) MID is encoded by the minus mating-type locus or male sex-determining region of heterothallic volvocine species and dominantly determines minus or male gametic differentiation. However, the factor(s) responsible for establishing the default plus or female differentiation programs have remained elusive. We performed a phylo-transcriptomic screen for autosomal RWP-RK TFs induced during gametogenesis in unicellular isogamous Chlamydomonas reinhardtii (Chlamydomonas) and in multicellular oogamous Volvox carteri (Volvox) and identified a single conserved ortho-group we named Volvocine Sex Regulator 1 (VSR1). Chlamydomonas vsr1 mutants of either mating type failed to mate and could not induce expression of key mating-type-specific genes. Similarly, Volvox vsr1 mutants in either sex could initiate sexual embryogenesis, but the presumptive eggs or androgonidia (sperm packet precursors) were infertile and unable to express key sex-specific genes. Yeast two-hybrid assays identified a conserved domain in VSR1 capable of self-interaction or interaction with the conserved N terminal domain of MID. In vivo coimmunoprecipitation experiments demonstrated association of VSR1 and MID in both Chlamydomonas and Volvox. These data support a new model for volvocine sexual differentiation where VSR1 homodimers activate expression of plus/female gamete-specific-genes, but when MID is present, MID-VSR1 heterodimers are preferentially formed and activate minus/male gamete-specific-genes.}, } @article {pmid37436868, year = {2023}, author = {Mondal, A and Bansal, MS}, title = {Generalizing the Domain-Gene-Species Reconciliation Framework to Microbial Genes and Domains.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TCBB.2023.3294480}, pmid = {37436868}, issn = {1557-9964}, abstract = {Protein domains play an important role in the function and evolution of many gene families. Previous studies have shown that domains are frequently lost or gained during gene family evolution. Yet, most computational approaches for studying gene family evolution do not account for domain-level evolution within genes. To address this limitation, a new three-level reconciliation framework, called the Domain-Gene-Species (DGS) reconciliation model, has been recently developed to simultaneously model the evolution of a domain family inside one or more gene families and the evolution of those gene families inside a species tree. However, the existing model applies only to multi-cellular eukaryotes where horizontal gene transfer is negligible. In this work, we generalize the existing DGS reconciliation model by allowing for the spread of genes and domains across species boundaries through horizontal transfer. We show that the problem of computing optimal generalized DGS reconciliations, though NP-hard, is approximable to within a constant factor, where the specific approximation ratio depends on the "event costs" used. We provide two different approximation algorithms for the problem and demonstrate the impact of the generalized framework using both simulated and real biological data. Our results show that our new algorithms result in highly accurate reconstructions of domain family evolution for microbes.}, } @article {pmid37426350, year = {2023}, author = {Tonami, K and Hayashi, T and Uchijima, Y and Kanai, M and Yura, F and Mada, J and Sugahara, K and Kurihara, Y and Kominami, Y and Ushijima, T and Takubo, N and Liu, X and Tozawa, H and Kanai, Y and Tokihiro, T and Kurihara, H}, title = {Coordinated linear and rotational movements of endothelial cells compartmentalized by VE-cadherin drive angiogenic sprouting.}, journal = {iScience}, volume = {26}, number = {7}, pages = {107051}, pmid = {37426350}, issn = {2589-0042}, abstract = {Angiogenesis is a sequential process to extend new blood vessels from preexisting ones by sprouting and branching. During angiogenesis, endothelial cells (ECs) exhibit inhomogeneous multicellular behaviors referred to as "cell mixing," in which ECs repetitively exchange their relative positions, but the underlying mechanism remains elusive. Here we identified the coordinated linear and rotational movements potentiated by cell-cell contact as drivers of sprouting angiogenesis using in vitro and in silico approaches. VE-cadherin confers the coordinated linear motility that facilitated forward sprout elongation, although it is dispensable for rotational movement, which was synchronous without VE-cadherin. Mathematical modeling recapitulated the EC motility in the two-cell state and angiogenic morphogenesis with the effects of VE-cadherin-knockout. Finally, we found that VE-cadherin-dependent EC compartmentalization potentiated branch elongations, and confirmed this by mathematical simulation. Collectively, we propose a way to understand angiogenesis, based on unique EC behavioral properties that are partially dependent on VE-cadherin function.}, } @article {pmid37409939, year = {2023}, author = {Aanen, DK and van 't Padje, A and Auxier, B}, title = {Longevity of Fungal Mycelia and Nuclear Quality Checks: a New Hypothesis for the Role of Clamp Connections in Dikaryons.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {}, number = {}, pages = {e0002221}, doi = {10.1128/mmbr.00022-21}, pmid = {37409939}, issn = {1098-5557}, abstract = {This paper addresses the stability of mycelial growth in fungi and differences between ascomycetes and basidiomycetes. Starting with general evolutionary theories of multicellularity and the role of sex, we then discuss individuality in fungi. Recent research has demonstrated the deleterious consequences of nucleus-level selection in fungal mycelia, favoring cheaters with a nucleus-level benefit during spore formation but a negative effect on mycelium-level fitness. Cheaters appear to generally be loss-of-fusion (LOF) mutants, with a higher propensity to form aerial hyphae developing into asexual spores. Since LOF mutants rely on heterokaryosis with wild-type nuclei, we argue that regular single-spore bottlenecks can efficiently select against such cheater mutants. We then zoom in on ecological differences between ascomycetes being typically fast-growing but short-lived with frequent asexual-spore bottlenecks and basidiomycetes being generally slow-growing but long-lived and usually without asexual-spore bottlenecks. We argue that these life history differences have coevolved with stricter nuclear quality checks in basidiomycetes. Specifically, we propose a new function for clamp connections, structures formed during the sexual stage in ascomycetes and basidiomycetes but during somatic growth only in basidiomycete dikaryons. During dikaryon cell division, the two haploid nuclei temporarily enter a monokaryotic phase, by alternatingly entering a retrograde-growing clamp cell, which subsequently fuses with the subapical cell to recover the dikaryotic cell. We hypothesize that clamp connections act as screening devices for nuclear quality, with both nuclei continuously testing each other for fusion ability, a test that LOF mutants will fail. By linking differences in longevity of the mycelial phase to ecology and stringency of nuclear quality checks, we propose that mycelia have a constant and low lifetime cheating risk, irrespective of their size and longevity.}, } @article {pmid37406343, year = {2023}, author = {Ruiz-Trillo, I and Kin, K and Casacuberta, E}, title = {The Origin of Metazoan Multicellularity: A Potential Microbial Black Swan Event.}, journal = {Annual review of microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-micro-032421-120023}, pmid = {37406343}, issn = {1545-3251}, abstract = {The emergence of animals from their unicellular ancestors is a major evolutionary event. Thanks to the study of diverse close unicellular relatives of animals, we now have a better grasp of what the unicellular ancestor of animals was like. However, it is unclear how that unicellular ancestor of animals became the first animals. To explain this transition, two popular theories, the choanoblastaea and the synzoospore, have been proposed. We will revise and expose the flaws in these two theories while showing that, due to the limits of our current knowledge, the origin of animals is a biological black swan event. As such, the origin of animals defies retrospective explanations. Therefore, we should be extra careful not to fall for confirmation biases based on few data and, instead, embrace this uncertainty and be open to alternative scenarios. With the aim to broaden the potential explanations on how animals emerged, we here propose two novel and alternative scenarios. In any case, to find the answer to how animals evolved, additional data will be required, as will the hunt for microscopic creatures that are closely related to animals but have not yet been sampled and studied. Expected final online publication date for the Annual Review of Microbiology, Volume 77 is September 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, } @article {pmid37404470, year = {2023}, author = {Maytum, A and Edginton-White, B and Bonifer, C}, title = {Identification and characterization of enhancer elements controlling cell type-specific and signalling dependent chromatin programming during hematopoietic development.}, journal = {Stem cell investigation}, volume = {10}, number = {}, pages = {14}, pmid = {37404470}, issn = {2306-9759}, abstract = {The development of multi-cellular organisms from a single fertilized egg requires to differentially execute the information encoded in our DNA. This complex process is regulated by the interplay of transcription factors with a chromatin environment, both of which provide the epigenetic information maintaining cell-type specific gene expression patterns. Moreover, transcription factors and their target genes form vast interacting gene regulatory networks which can be exquisitely stable. However, all developmental processes originate from pluripotent precursor cell types. The production of terminally differentiated cells from such cells, therefore, requires successive changes of cell fates, meaning that genes relevant for the next stage of differentiation must be switched on and genes not relevant anymore must be switched off. The stimulus for the change of cell fate originates from extrinsic signals which set a cascade of intracellular processes in motion that eventually terminate at the genome leading to changes in gene expression and the development of alternate gene regulatory networks. How developmental trajectories are encoded in the genome and how the interplay between intrinsic and extrinsic processes regulates development is one of the major questions in developmental biology. The development of the hematopoietic system has long served as model to understand how changes in gene regulatory networks drive the differentiation of the various blood cell types. In this review, we highlight the main signals and transcription factors and how they are integrated at the level of chromatin programming and gene expression control. We also highlight recent studies identifying the cis-regulatory elements such as enhancers at the global level and explain how their developmental activity is regulated by the cooperation of cell-type specific and ubiquitous transcription factors with extrinsic signals.}, } @article {pmid37401921, year = {2023}, author = {Stevenson, ZC and Moerdyk-Schauwecker, MJ and Banse, SA and Patel, DS and Lu, H and Phillips, PC}, title = {High-throughput library transgenesis in Caenorhabditis elegans via Transgenic Arrays Resulting in Diversity of Integrated Sequences (TARDIS).}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37401921}, issn = {2050-084X}, support = {R01 AG056436/AG/NIA NIH HHS/United States ; R35 GM131838/GM/NIGMS NIH HHS/United States ; R01AG056436/NH/NIH HHS/United States ; R35GM131838/NH/NIH HHS/United States ; }, mesh = {Humans ; Animals ; *Caenorhabditis elegans/genetics ; Transgenes ; Animals, Genetically Modified ; *Gene Transfer Techniques ; Gene Library ; }, abstract = {High-throughput transgenesis using synthetic DNA libraries is a powerful method for systematically exploring genetic function. Diverse synthesized libraries have been used for protein engineering, identification of protein-protein interactions, characterization of promoter libraries, developmental and evolutionary lineage tracking, and various other exploratory assays. However, the need for library transgenesis has effectively restricted these approaches to single-cell models. Here, we present Transgenic Arrays Resulting in Diversity of Integrated Sequences (TARDIS), a simple yet powerful approach to large-scale transgenesis that overcomes typical limitations encountered in multicellular systems. TARDIS splits the transgenesis process into a two-step process: creation of individuals carrying experimentally introduced sequence libraries, followed by inducible extraction and integration of individual sequences/library components from the larger library cassette into engineered genomic sites. Thus, transformation of a single individual, followed by lineage expansion and functional transgenesis, gives rise to thousands of genetically unique transgenic individuals. We demonstrate the power of this system using engineered, split selectable TARDIS sites in Caenorhabditis elegans to generate (1) a large set of individually barcoded lineages and (2) transcriptional reporter lines from predefined promoter libraries. We find that this approach increases transformation yields up to approximately 1000-fold over current single-step methods. While we demonstrate the utility of TARDIS using C. elegans, in principle the process is adaptable to any system where experimentally generated genomic loci landing pads and diverse, heritable DNA elements can be generated.}, } @article {pmid37384647, year = {2023}, author = {Kapsetaki, SE and Fortunato, A and Compton, Z and Rupp, SM and Nour, Z and Riggs-Davis, S and Stephenson, D and Duke, EG and Boddy, AM and Harrison, TM and Maley, CC and Aktipis, A}, title = {Is chimerism associated with cancer across the tree of life?.}, journal = {PloS one}, volume = {18}, number = {6}, pages = {e0287901}, pmid = {37384647}, issn = {1932-6203}, mesh = {Animals ; *Chimerism ; *Neoplasms/genetics ; Problem Solving ; Mammals ; }, abstract = {Chimerism is a widespread phenomenon across the tree of life. It is defined as a multicellular organism composed of cells from other genetically distinct entities. This ability to 'tolerate' non-self cells may be linked to susceptibility to diseases like cancer. Here we test whether chimerism is associated with cancers across obligately multicellular organisms in the tree of life. We classified 12 obligately multicellular taxa from lowest to highest chimerism levels based on the existing literature on the presence of chimerism in these species. We then tested for associations of chimerism with tumour invasiveness, neoplasia (benign or malignant) prevalence and malignancy prevalence in 11 terrestrial mammalian species. We found that taxa with higher levels of chimerism have higher tumour invasiveness, though there was no association between malignancy or neoplasia and chimerism among mammals. This suggests that there may be an important biological relationship between chimerism and susceptibility to tissue invasion by cancerous cells. Studying chimerism might help us identify mechanisms underlying invasive cancers and also could provide insights into the detection and management of emerging transmissible cancers.}, } @article {pmid37384391, year = {2023}, author = {Römling, U and Cao, LY and Bai, FW}, title = {Evolution of cyclic di-GMP signalling on a short and long term time scale.}, journal = {Microbiology (Reading, England)}, volume = {169}, number = {6}, pages = {}, pmid = {37384391}, issn = {1465-2080}, mesh = {Humans ; *Signal Transduction ; *Second Messenger Systems ; Amino Acid Substitution ; Biofilms ; Gene Transfer, Horizontal ; }, abstract = {Diversifying radiation of domain families within specific lineages of life indicates the importance of their functionality for the organisms. The foundation for the diversifying radiation of the cyclic di-GMP signalling network that occurred within the bacterial kingdom is most likely based in the outmost adaptability, flexibility and plasticity of the system. Integrative sensing of multiple diverse extra- and intracellular signals is made possible by the N-terminal sensory domains of the modular cyclic di-GMP turnover proteins, mutations in the protein scaffolds and subsequent signal reception by diverse receptors, which eventually rewires opposite host-associated as well as environmental life styles including parallel regulated target outputs. Natural, laboratory and microcosm derived microbial variants often with an altered multicellular biofilm behaviour as reading output demonstrated single amino acid substitutions to substantially alter catalytic activity including substrate specificity. Truncations and domain swapping of cyclic di-GMP signalling genes and horizontal gene transfer suggest rewiring of the network. Presence of cyclic di-GMP signalling genes on horizontally transferable elements in particular observed in extreme acidophilic bacteria indicates that cyclic di-GMP signalling and biofilm components are under selective pressure in these types of environments. On a short and long term evolutionary scale, within a species and in families within bacterial orders, respectively, the cyclic di-GMP signalling network can also rapidly disappear. To investigate variability of the cyclic di-GMP signalling system on various levels will give clues about evolutionary forces and discover novel physiological and metabolic pathways affected by this intriguing second messenger signalling system.}, } @article {pmid37382119, year = {2023}, author = {Saritas, T}, title = {The use of tissue clearing to study renal transport mechanisms and kidney remodelling.}, journal = {Current opinion in nephrology and hypertension}, volume = {32}, number = {5}, pages = {458-466}, doi = {10.1097/MNH.0000000000000904}, pmid = {37382119}, issn = {1473-6543}, mesh = {Animals ; Humans ; *Imaging, Three-Dimensional/methods ; *Kidney ; }, abstract = {PURPOSE OF REVIEW: Tissue clearing enables examination of biological structures at subcellular resolution in three dimensions. It uncovered the spatial and temporal plasticity of multicellular kidney structures that occur during homeostatic stress. This article will review the recent development in tissue clearing protocols and how it facilitated the study of renal transport mechanisms and remodelling of the kidney.

RECENT FINDINGS: Tissue clearing methods have evolved from primarily labelling proteins in thin tissue or individual organs to visualizing both RNA and protein simultaneously in whole animals or human organs. The use of small antibody fragments and innovative imaging techniques improved immunolabelling and resolution. These advances opened up new avenues for studying organ crosstalk and diseases that affect multiple parts of the organism. Accumulating evidence suggests that tubule remodelling can occur rapidly in response to homeostatic stress or injury, allowing for adjustments in the quantitative expression of renal transporters. Tissue clearing helped to better understand the development of tubule cystogenesis, renal hypertension and salt wasting syndromes, and revealed potential progenitor cells in the kidney.

SUMMARY: The continued evolution and improvement of tissue clearing methods can help to gain deep biological insights into the structure and function of the kidney, which will have clinical implications.}, } @article {pmid37379342, year = {2023}, author = {Zare, M and Mirhoseini, SZ and Ghovvati, S and Yakhkeshi, S and Hesaraki, M and Barati, M and Sayyahpour, FA and Baharvand, H and Hassani, SN}, title = {The constitutively active pSMAD2/3 relatively improves the proliferation of chicken primordial germ cells.}, journal = {Molecular reproduction and development}, volume = {90}, number = {6}, pages = {339-357}, doi = {10.1002/mrd.23689}, pmid = {37379342}, issn = {1098-2795}, mesh = {Animals ; *Chickens/metabolism ; *Transforming Growth Factor beta/metabolism ; Transcription Factors/metabolism ; Germ Cells ; Cell Proliferation ; Cells, Cultured ; }, abstract = {In many multicellular organisms, mature gametes originate from primordial germ cells (PGCs). Improvements in the culture of PGCs are important not only for developmental biology research, but also for preserving endangered species, and for genome editing and transgenic animal technologies. SMAD2/3 appear to be powerful regulators of gene expression; however, their potential positive impact on the regulation of PGC proliferation has not been taken into consideration. Here, the effect of TGF-β signaling as the upstream activator of SMAD2/3 transcription factors was evaluated on chicken PGCs' proliferation. For this, chicken PGCs at stages 26-28 Hamburger-Hamilton were obtained from the embryonic gonadal regions and cultured on different feeders or feeder-free substrates. The results showed that TGF-β signaling agonists (IDE1 and Activin-A) improved PGC proliferation to some extent while treatment with SB431542, the antagonist of TGF-β, disrupted PGCs' proliferation. However, the transfection of PGCs with constitutively active SMAD2/3 (SMAD2/3CA) resulted in improved PGC proliferation for more than 5 weeks. The results confirmed the interactions between overexpressed SMAD2/3CA and pluripotency-associated genes NANOG, OCT4, and SOX2. According to the results, the application of SMAD2/3CA could represent a step toward achieving an efficient expansion of avian PGCs.}, } @article {pmid37378290, year = {2023}, author = {Bacci, G and Fratini, S and Meriggi, N and Cheng, CLY and Ng, KH and Pindo, M and Iannucci, A and Mengoni, A and Cavalieri, D and Cannicci, S}, title = {Conserved organ-specific microbial assemblages in different populations of a terrestrial crab.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1113617}, pmid = {37378290}, issn = {1664-302X}, abstract = {Microorganisms are ubiquitous in the environment and provide genetic and physiological functions to multicellular organisms. Knowledge on the associated microbiota is becoming highly relevant to understand the host's ecology and biology. Among invertebrates, many examples of endosymbiosis have been described, such as those in corals, ants, and termites. At present, however, little is known on the presence, diversity, and putative roles of the microbiota associated to brachyuran crabs in relation to their environment. In this work we investigated the associated microbiota of three populations of the terrestrial brachyuran crab Chiromantes haematocheir to find evidence of a conserved organ-specific microbiome unrelated to the population of origin and dissimilar from environmental microbial assemblages. Bacterial 16S rRNA gene and fungal ITS sequences were obtained from selected crab organs and environmental matrices to profile microbial communities. Despite the presence of truly marine larval stages and the absence of a gregarious behaviour, favouring microbiota exchanges, we found common, organ-specific microbiota, associated with the gut and the gills of crabs from the different populations (with more than 15% of the genera detected specifically enriched only in one organ). These findings suggest the presence of possible functional roles of the organ-specific microbiota.}, } @article {pmid37367479, year = {2023}, author = {Dhouailly, D}, title = {Evo Devo of the Vertebrates Integument.}, journal = {Journal of developmental biology}, volume = {11}, number = {2}, pages = {}, pmid = {37367479}, issn = {2221-3759}, abstract = {All living jawed vertebrates possess teeth or did so ancestrally. Integumental surface also includes the cornea. Conversely, no other anatomical feature differentiates the clades so readily as skin appendages do, multicellular glands in amphibians, hair follicle/gland complexes in mammals, feathers in birds, and the different types of scales. Tooth-like scales are characteristic of chondrichthyans, while mineralized dermal scales are characteristic of bony fishes. Corneous epidermal scales might have appeared twice, in squamates, and on feet in avian lineages, but posteriorly to feathers. In contrast to the other skin appendages, the origin of multicellular glands of amphibians has never been addressed. In the seventies, pioneering dermal-epidermal recombination between chick, mouse and lizard embryos showed that: (1) the clade type of the appendage is determined by the epidermis; (2) their morphogenesis requires two groups of dermal messages, first for primordia formation, second for appendage final architecture; (3) the early messages were conserved during amniotes evolution. Molecular biology studies that have identified the involved pathways, extending those data to teeth and dermal scales, suggest that the different vertebrate skin appendages evolved in parallel from a shared placode/dermal cells unit, present in a common toothed ancestor, c.a. 420 mya.}, } @article {pmid37353784, year = {2023}, author = {Fang, H and Sun, Q and Zhou, J and Zhang, H and Song, Q and Zhang, H and Yu, G and Guo, Y and Huang, C and Mou, Y and Jia, C and Song, Y and Liu, A and Song, K and Lu, C and Tian, R and Wei, S and Yang, D and Chen, Y and Li, T and Wang, K and Yu, Y and Lv, Y and Mo, K and Sun, P and Yu, X and Song, X}, title = {m[6]A methylation reader IGF2BP2 activates endothelial cells to promote angiogenesis and metastasis of lung adenocarcinoma.}, journal = {Molecular cancer}, volume = {22}, number = {1}, pages = {99}, pmid = {37353784}, issn = {1476-4598}, support = {ts20190991//Taishan Scholars Project/ ; ZR2021MH323//The Natural Science Fund of Shandong Province grant/ ; 2022YD037//The Science and Technology Innovation Development Plan of Yantai/ ; 201909370036//China Scholarship Council/ ; 82103646//The National Natural Science Fund of China grant/ ; }, mesh = {Humans ; Methylation ; Ecosystem ; Endothelial Cells ; Phosphatidylinositol 3-Kinases ; Neoplasm Recurrence, Local ; *Adenocarcinoma of Lung/genetics ; *Lung Neoplasms/genetics ; Tumor Microenvironment ; RNA-Binding Proteins/genetics ; }, abstract = {BACKGROUND: Lung adenocarcinoma (LUAD) is a common type of lung cancer with a high risk of metastasis, but the exact molecular mechanisms of metastasis are not yet understood.

METHODS: This study acquired single-cell transcriptomics profiling of 11 distal normal lung tissues, 11 primary LUAD tissues, and 4 metastatic LUAD tissues from the GSE131907 dataset. The lung multicellular ecosystems were characterized at a single-cell resolution, and the potential mechanisms underlying angiogenesis and metastasis of LUAD were explored.

RESULTS: We constructed a global single-cell landscape of 93,610 cells from primary and metastatic LUAD and found that IGF2BP2 was specifically expressed both in a LUAD cell subpopulation (termed as LUAD_IGF2BP2), and an endothelial cell subpopulation (termed as En_IGF2BP2). The LUAD_IGF2BP2 subpopulation progressively formed and dominated the ecology of metastatic LUAD during metastatic evolution. IGF2BP2 was preferentially secreted by exosomes in the LUAD_IGF2BP2 subpopulation, which was absorbed by the En_IGF2BP2 subpopulation in the tumor microenvironment. Subsequently, IGF2BP2 improved the RNA stability of FLT4 through m[6]A modification, thereby activating the PI3K-Akt signaling pathway, and eventually promoting angiogenesis and metastasis. Analysis of clinical data showed that IGF2BP2 was linked with poor overall survival and relapse-free survival for LUAD patients.

CONCLUSIONS: Overall, these findings provide a novel insight into the multicellular ecosystems of primary and metastatic LUAD, and demonstrate that a specific LUAD_IGF2BP2 subpopulation is a key orchestrator promoting angiogenesis and metastasis, with implications for the gene regulatory mechanisms of LUAD metastatic evolution, representing themselves as potential antiangiogenic targets.}, } @article {pmid37351542, year = {2023}, author = {Nagy, LG and Vonk, PJ and Künzler, M and Földi, C and Virágh, M and Ohm, RA and Hennicke, F and Bálint, B and Csernetics, Á and Hegedüs, B and Hou, Z and Liu, XB and Nan, S and Pareek, M and Sahu, N and Szathmári, B and Varga, T and Wu, H and Yang, X and Merényi, Z}, title = {Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes.}, journal = {Studies in mycology}, volume = {104}, number = {}, pages = {1-85}, pmid = {37351542}, issn = {0166-0616}, abstract = {Fruiting bodies (sporocarps, sporophores or basidiomata) of mushroom-forming fungi (Agaricomycetes) are among the most complex structures produced by fungi. Unlike vegetative hyphae, fruiting bodies grow determinately and follow a genetically encoded developmental program that orchestrates their growth, tissue differentiation and sexual sporulation. In spite of more than a century of research, our understanding of the molecular details of fruiting body morphogenesis is still limited and a general synthesis on the genetics of this complex process is lacking. In this paper, we aim at a comprehensive identification of conserved genes related to fruiting body morphogenesis and distil novel functional hypotheses for functionally poorly characterised ones. As a result of this analysis, we report 921 conserved developmentally expressed gene families, only a few dozens of which have previously been reported to be involved in fruiting body development. Based on literature data, conserved expression patterns and functional annotations, we provide hypotheses on the potential role of these gene families in fruiting body development, yielding the most complete description of molecular processes in fruiting body morphogenesis to date. We discuss genes related to the initiation of fruiting, differentiation, growth, cell surface and cell wall, defence, transcriptional regulation as well as signal transduction. Based on these data we derive a general model of fruiting body development, which includes an early, proliferative phase that is mostly concerned with laying out the mushroom body plan (via cell division and differentiation), and a second phase of growth via cell expansion as well as meiotic events and sporulation. Altogether, our discussions cover 1 480 genes of Coprinopsis cinerea, and their orthologs in Agaricus bisporus, Cyclocybe aegerita, Armillaria ostoyae, Auriculariopsis ampla, Laccaria bicolor, Lentinula edodes, Lentinus tigrinus, Mycena kentingensis, Phanerochaete chrysosporium, Pleurotus ostreatus, and Schizophyllum commune, providing functional hypotheses for ~10 % of genes in the genomes of these species. Although experimental evidence for the role of these genes will need to be established in the future, our data provide a roadmap for guiding functional analyses of fruiting related genes in the Agaricomycetes. We anticipate that the gene compendium presented here, combined with developments in functional genomics approaches will contribute to uncovering the genetic bases of one of the most spectacular multicellular developmental processes in fungi. Citation: Nagy LG, Vonk PJ, Künzler M, Földi C, Virágh M, Ohm RA, Hennicke F, Bálint B, Csernetics Á, Hegedüs B, Hou Z, Liu XB, Nan S, M. Pareek M, Sahu N, Szathmári B, Varga T, Wu W, Yang X, Merényi Z (2023). Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes. Studies in Mycology 104: 1-85. doi: 10.3114/sim.2022.104.01.}, } @article {pmid37349567, year = {2023}, author = {Merényi, Z and Krizsán, K and Sahu, N and Liu, XB and Bálint, B and Stajich, JE and Spatafora, JW and Nagy, LG}, title = {Genomes of fungi and relatives reveal delayed loss of ancestral gene families and evolution of key fungal traits.}, journal = {Nature ecology & evolution}, volume = {7}, number = {8}, pages = {1221-1231}, pmid = {37349567}, issn = {2397-334X}, support = {758161//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; }, abstract = {Fungi are ecologically important heterotrophs that have radiated into most niches on Earth and fulfil key ecological services. Despite intense interest in their origins, major genomic trends of their evolutionary route from a unicellular opisthokont ancestor to derived multicellular fungi remain poorly known. Here we provide a highly resolved genome-wide catalogue of gene family changes across fungal evolution inferred from the genomes of 123 fungi and relatives. We show that a dominant trend in early fungal evolution has been the gradual shedding of protist genes and the punctuated emergence of innovation by two main gene duplication events. We find that the gene content of non-Dikarya fungi resembles that of unicellular opisthokonts in many respects, owing to the conservation of protist genes in their genomes. The most rapidly duplicating gene groups included extracellular proteins and transcription factors, as well as ones linked to the coordination of nutrient uptake with growth, highlighting the transition to a sessile osmotrophic feeding strategy and subsequent lifestyle evolution as important elements of early fungal history. These results suggest that the genomes of pre-fungal ancestors evolved into the typical filamentous fungal genome by a combination of gradual gene loss, turnover and several large duplication events rather than by abrupt changes. Consequently, the taxonomically defined Fungi represents a genomically non-uniform assemblage of species.}, } @article {pmid37342564, year = {2023}, author = {Zhao, Y and Zhang, W and Pan, H and Chen, J and Cui, K and Wu, LF and Lin, W and Xiao, T and Zhang, W and Liu, J}, title = {Insight into the metabolic potential and ecological function of a novel Magnetotactic Nitrospirota in coral reef habitat.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1182330}, pmid = {37342564}, issn = {1664-302X}, abstract = {Magnetotactic bacteria (MTB) within the Nitrospirota phylum play important roles in biogeochemical cycles due to their outstanding ability to biomineralize large amounts of magnetite magnetosomes and intracellular sulfur globules. For several decades, Nitrospirota MTB were believed to only live in freshwater or low-salinity environments. While this group have recently been found in marine sediments, their physiological features and ecological roles have remained unclear. In this study, we combine electron microscopy with genomics to characterize a novel population of Nitrospirota MTB in a coral reef area of the South China Sea. Both phylogenetic and genomic analyses revealed it as representative of a novel genus, named as Candidatus Magnetocorallium paracelense XS-1. The cells of XS-1 are small and vibrioid-shaped, and have bundled chains of bullet-shaped magnetite magnetosomes, sulfur globules, and cytoplasmic vacuole-like structures. Genomic analysis revealed that XS-1 has the potential to respire sulfate and nitrate, and utilize the Wood-Ljungdahl pathway for carbon fixation. XS-1 has versatile metabolic traits that make it different from freshwater Nitrospirota MTB, including Pta-ackA pathway, anaerobic sulfite reduction, and thiosulfate disproportionation. XS-1 also encodes both the cbb3-type and the aa3-type cytochrome c oxidases, which may function as respiratory energy-transducing enzymes under high oxygen conditions and anaerobic or microaerophilic conditions, respectively. XS-1 has multiple copies of circadian related genes in response to variability in coral reef habitat. Our results implied that XS-1 has a remarkable plasticity to adapt the environment and can play a beneficial role in coral reef ecosystems.}, } @article {pmid37338964, year = {2023}, author = {Caspi, Y and Pantazopoulou, CK and Prompers, JJ and Pieterse, CMJ and Hulshoff Pol, H and Kajala, K}, title = {Why did glutamate, GABA, and melatonin become intercellular signalling molecules in plants?.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37338964}, issn = {2050-084X}, mesh = {Animals ; *Melatonin/metabolism ; Glutamic Acid/metabolism ; Plants/metabolism ; gamma-Aminobutyric Acid/metabolism ; Signal Transduction ; }, abstract = {Intercellular signalling is an indispensable part of multicellular life. Understanding the commonalities and differences in how signalling molecules function in two remote branches of the tree of life may shed light on the reasons these molecules were originally recruited for intercellular signalling. Here we review the plant function of three highly studied animal intercellular signalling molecules, namely glutamate, γ-aminobutyric acid (GABA), and melatonin. By considering both their signalling function in plants and their broader physiological function, we suggest that molecules with an original function as key metabolites or active participants in reactive ion species scavenging have a high chance of becoming intercellular signalling molecules. Naturally, the evolution of machinery to transduce a message across the plasma membrane is necessary. This fact is demonstrated by three other well-studied animal intercellular signalling molecules, namely serotonin, dopamine, and acetylcholine, for which there is currently no evidence that they act as intercellular signalling molecules in plants.}, } @article {pmid37333256, year = {2023}, author = {Montrose, K and Lac, DT and Burnetti, AJ and Tong, K and Bozdag, GO and Hukkanen, M and Ratcliff, WC and Saarikangas, J}, title = {Proteostatic tuning underpins the evolution of novel multicellular traits.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.05.31.543183}, pmid = {37333256}, abstract = {UNLABELLED: The evolution of multicellularity paved the way for the origin of complex life on Earth, but little is known about the mechanistic basis of early multicellular evolution. Here, we examine the molecular basis of multicellular adaptation in the Multicellularity Long Term Evolution Experiment (MuLTEE). We demonstrate that cellular elongation, a key adaptation underpinning increased biophysical toughness and organismal size, is convergently driven by downregulation of the chaperone Hsp90. Mechanistically, Hsp90-mediated morphogenesis operates by destabilizing the cyclin-dependent kinase Cdc28, resulting in delayed mitosis and prolonged polarized growth. Reintroduction of Hsp90 expression resulted in shortened cells that formed smaller groups with reduced multicellular fitness. Together, our results show how ancient protein folding systems can be tuned to drive rapid evolution at a new level of biological individuality by revealing novel developmental phenotypes.

ONE SENTENCE SUMMARY: Downregulation of Hsp90 decouples cell cycle progression and growth to drive the evolution of macroscopic multicellularity.}, } @article {pmid37333112, year = {2023}, author = {Keller, A and Gao, LL and Witten, D and Dunham, MJ}, title = {Condition-dependent fitness effects of large synthetic chromosome amplifications.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37333112}, support = {P41 GM103533/GM/NIGMS NIH HHS/United States ; R01 GM147040/GM/NIGMS NIH HHS/United States ; T32 HG000035/HG/NHGRI NIH HHS/United States ; }, abstract = {Whole-chromosome aneuploidy and large segmental amplifications can have devastating effects in multicellular organisms, from developmental disorders and miscarriage to cancer. Aneuploidy in single-celled organisms such as yeast also results in proliferative defects and reduced viability. Yet, paradoxically, CNVs are routinely observed in laboratory evolution experiments with microbes grown in stressful conditions. The defects associated with aneuploidy are often attributed to the imbalance of many differentially expressed genes on the affected chromosomes, with many genes each contributing incremental effects. An alternate hypothesis is that a small number of individual genes are large effect 'drivers' of these fitness changes when present in an altered copy number. To test these two views, we have employed a collection of strains bearing large chromosomal amplifications that we previously assayed in nutrient-limited chemostat competitions. In this study, we focus on conditions known to be poorly tolerated by aneuploid yeast-high temperature, treatment with the Hsp90 inhibitor radicicol, and growth in extended stationary phase. To identify potential genes with a large impact on fitness, we fit a piecewise constant model to fitness data across chromosome arms, filtering breakpoints in this model by magnitude to focus on regions with a large impact on fitness in each condition. While fitness generally decreased as the length of the amplification increased, we were able to identify 91 candidate regions that disproportionately impacted fitness when amplified. Consistent with our previous work with this strain collection, nearly all candidate regions were condition specific, with only five regions impacting fitness in multiple conditions.}, } @article {pmid37322016, year = {2023}, author = {Chavhan, Y and Dey, S and Lind, PA}, title = {Bacteria evolve macroscopic multicellularity by the genetic assimilation of phenotypically plastic cell clustering.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3555}, pmid = {37322016}, issn = {2041-1723}, mesh = {*Biological Evolution ; *Eukaryota ; Adaptation, Physiological ; Phenotype ; Bacteria ; }, abstract = {The evolutionary transition from unicellularity to multicellularity was a key innovation in the history of life. Experimental evolution is an important tool to study the formation of undifferentiated cellular clusters, the likely first step of this transition. Although multicellularity first evolved in bacteria, previous experimental evolution research has primarily used eukaryotes. Moreover, it focuses on mutationally driven (and not environmentally induced) phenotypes. Here we show that both Gram-negative and Gram-positive bacteria exhibit phenotypically plastic (i.e., environmentally induced) cell clustering. Under high salinity, they form elongated clusters of ~ 2 cm. However, under habitual salinity, the clusters disintegrate and grow planktonically. We used experimental evolution with Escherichia coli to show that such clustering can be assimilated genetically: the evolved bacteria inherently grow as macroscopic multicellular clusters, even without environmental induction. Highly parallel mutations in genes linked to cell wall assembly formed the genomic basis of assimilated multicellularity. While the wildtype also showed cell shape plasticity across high versus low salinity, it was either assimilated or reversed after evolution. Interestingly, a single mutation could genetically assimilate multicellularity by modulating plasticity at multiple levels of organization. Taken together, we show that phenotypic plasticity can prime bacteria for evolving undifferentiated macroscopic multicellularity.}, } @article {pmid37316485, year = {2023}, author = {Seabloom, EW and Caldeira, MC and Davies, KF and Kinkel, L and Knops, JMH and Komatsu, KJ and MacDougall, AS and May, G and Millican, M and Moore, JL and Perez, LI and Porath-Krause, AJ and Power, SA and Prober, SM and Risch, AC and Stevens, C and Borer, ET}, title = {Globally consistent response of plant microbiome diversity across hosts and continents to soil nutrients and herbivores.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3516}, pmid = {37316485}, issn = {2041-1723}, mesh = {*Herbivory ; Biomass ; *Microbiota ; Nutrients ; Soil ; }, abstract = {All multicellular organisms host a diverse microbiome composed of microbial pathogens, mutualists, and commensals, and changes in microbiome diversity or composition can alter host fitness and function. Nonetheless, we lack a general understanding of the drivers of microbiome diversity, in part because it is regulated by concurrent processes spanning scales from global to local. Global-scale environmental gradients can determine variation in microbiome diversity among sites, however an individual host's microbiome also may reflect its local micro-environment. We fill this knowledge gap by experimentally manipulating two potential mediators of plant microbiome diversity (soil nutrient supply and herbivore density) at 23 grassland sites spanning global-scale gradients in soil nutrients, climate, and plant biomass. Here we show that leaf-scale microbiome diversity in unmanipulated plots depended on the total microbiome diversity at each site, which was highest at sites with high soil nutrients and plant biomass. We also found that experimentally adding soil nutrients and excluding herbivores produced concordant results across sites, increasing microbiome diversity by increasing plant biomass, which created a shaded microclimate. This demonstration of consistent responses of microbiome diversity across a wide range of host species and environmental conditions suggests the possibility of a general, predictive understanding of microbiome diversity.}, } @article {pmid37295595, year = {2023}, author = {Jacob, MS}, title = {Toward a Bio-Organon: A model of interdependence between energy, information and knowledge in living systems.}, journal = {Bio Systems}, volume = {230}, number = {}, pages = {104939}, doi = {10.1016/j.biosystems.2023.104939}, pmid = {37295595}, issn = {1872-8324}, mesh = {Humans ; *Biological Evolution ; *Models, Theoretical ; }, abstract = {What is an organism? In the absence of a fundamental biological definition, what constitutes a living organism, whether it is a unicellular microbe, a multicellular being or a multi-organismal society, remains an open question. New models of living systems are needed to address the scale of this question, with implications for the relationship between humanity and planetary ecology. Here we develop a generic model of an organism that can be applied across multiple scales and through major evolutionary transitions to form a toolkit, or bio-organon, for theoretical studies of planetary-wide physiology. The tool identifies the following core organismic principles that cut across spatial scale: (1) evolvability through self-knowledge, (2) entanglement between energy and information, and (3) extrasomatic "technology" to scaffold increases in spatial scale. Living systems are generally defined by their ability to self-sustain against entropic forces of degradation. Life "knows" how to survive from the inside, not from its genetic code alone, but by utilizing this code through dynamically embodied and functionally specialized flows of information and energy. That is, entangled metabolic and communication networks bring encoded knowledge to life in order to sustain life. However, knowledge is itself evolved and is evolving. The functional coupling between knowledge, energy and information has ancient origins, enabling the original, cellular "biotechnology," and cumulative evolutionary creativity in biochemical products and forms. Cellular biotechnology also enabled the nesting of specialized cells into multicellular organisms. This nested organismal hierarchy can be extended further, suggesting that an organism of organisms, or a human "superorganism," is not only possible, but in keeping with evolutionary trends.}, } @article {pmid37285440, year = {2023}, author = {Zhang, F and Ji, Q and Chaturvedi, J and Morales, M and Mao, Y and Meng, X and Dong, L and Deng, J and Qian, SB and Xiang, Y}, title = {Human SAMD9 is a poxvirus-activatable anticodon nuclease inhibiting codon-specific protein synthesis.}, journal = {Science advances}, volume = {9}, number = {23}, pages = {eadh8502}, pmid = {37285440}, issn = {2375-2548}, support = {R01 AI151638/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Anticodon/genetics ; *RNA, Transfer, Phe/genetics/metabolism ; Codon ; RNA, Transfer/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; }, abstract = {As a defense strategy against viruses or competitors, some microbes use anticodon nucleases (ACNases) to deplete essential tRNAs, effectively halting global protein synthesis. However, this mechanism has not been observed in multicellular eukaryotes. Here, we report that human SAMD9 is an ACNase that specifically cleaves phenylalanine tRNA (tRNA[Phe]), resulting in codon-specific ribosomal pausing and stress signaling. While SAMD9 ACNase activity is normally latent in cells, it can be activated by poxvirus infection or rendered constitutively active by SAMD9 mutations associated with various human disorders, revealing tRNA[Phe] depletion as an antiviral mechanism and a pathogenic condition in SAMD9 disorders. We identified the N-terminal effector domain of SAMD9 as the ACNase, with substrate specificity primarily determined by a eukaryotic tRNA[Phe]-specific 2'-O-methylation at the wobble position, making virtually all eukaryotic tRNA[Phe] susceptible to SAMD9 cleavage. Notably, the structure and substrate specificity of SAMD9 ACNase differ from known microbial ACNases, suggesting convergent evolution of a common immune defense strategy targeting tRNAs.}, } @article {pmid37264211, year = {2023}, author = {Lamolle, G and Simón, D and Iriarte, A and Musto, H}, title = {Main Factors Shaping Amino Acid Usage Across Evolution.}, journal = {Journal of molecular evolution}, volume = {91}, number = {4}, pages = {382-390}, pmid = {37264211}, issn = {1432-1432}, mesh = {Animals ; *Amino Acids/genetics ; Codon/genetics ; *Genetic Code ; Base Composition ; Proteome/genetics ; Evolution, Molecular ; Mammals/genetics ; }, abstract = {The standard genetic code determines that in most species, including viruses, there are 20 amino acids that are coded by 61 codons, while the other three codons are stop triplets. Considering the whole proteome each species features its own amino acid frequencies, given the slow rate of change, closely related species display similar GC content and amino acids usage. In contrast, distantly related species display different amino acid frequencies. Furthermore, within certain multicellular species, as mammals, intragenomic differences in the usage of amino acids are evident. In this communication, we shall summarize some of the most prominent and well-established factors that determine the differences found in the amino acid usage, both across evolution and intragenomically.}, } @article {pmid37264002, year = {2023}, author = {Galand, PE and Ruscheweyh, HJ and Salazar, G and Hochart, C and Henry, N and Hume, BCC and Oliveira, PH and Perdereau, A and Labadie, K and Belser, C and Boissin, E and Romac, S and Poulain, J and Bourdin, G and Iwankow, G and Moulin, C and Armstrong, EJ and Paz-García, DA and Ziegler, M and Agostini, S and Banaigs, B and Boss, E and Bowler, C and de Vargas, C and Douville, E and Flores, M and Forcioli, D and Furla, P and Gilson, E and Lombard, F and Pesant, S and Reynaud, S and Thomas, OP and Troublé, R and Zoccola, D and Voolstra, CR and Thurber, RV and Sunagawa, S and Wincker, P and Allemand, D and Planes, S}, title = {Diversity of the Pacific Ocean coral reef microbiome.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3039}, pmid = {37264002}, issn = {2041-1723}, mesh = {Animals ; Coral Reefs ; Pacific Ocean ; *Anthozoa ; Biodiversity ; *Microbiota ; Fishes ; Plankton ; }, abstract = {Coral reefs are among the most diverse ecosystems on Earth. They support high biodiversity of multicellular organisms that strongly rely on associated microorganisms for health and nutrition. However, the extent of the coral reef microbiome diversity and its distribution at the oceanic basin-scale remains to be explored. Here, we systematically sampled 3 coral morphotypes, 2 fish species, and planktonic communities in 99 reefs from 32 islands across the Pacific Ocean, to assess reef microbiome composition and biogeography. We show a very large richness of reef microorganisms compared to other environments, which extrapolated to all fishes and corals of the Pacific, approximates the current estimated total prokaryotic diversity for the entire Earth. Microbial communities vary among and within the 3 animal biomes (coral, fish, plankton), and geographically. For corals, the cross-ocean patterns of diversity are different from those known for other multicellular organisms. Within each coral morphotype, community composition is always determined by geographic distance first, both at the island and across ocean scale, and then by environment. Our unprecedented sampling effort of coral reef microbiomes, as part of the Tara Pacific expedition, provides new insight into the global microbial diversity, the factors driving their distribution, and the biocomplexity of reef ecosystems.}, } @article {pmid37256696, year = {2023}, author = {Blomme, J and Wichard, T and Jacobs, TB and De Clerck, O}, title = {Ulva: An emerging green seaweed model for systems biology.}, journal = {Journal of phycology}, volume = {59}, number = {3}, pages = {433-440}, doi = {10.1111/jpy.13341}, pmid = {37256696}, issn = {1529-8817}, mesh = {*Ulva ; *Seaweed ; Ecosystem ; Systems Biology ; *Chlorophyta ; }, abstract = {Green seaweeds exhibit a wide range of morphologies and occupy various ecological niches, spanning from freshwater to marine and terrestrial habitats. These organisms, which predominantly belong to the class Ulvophyceae, showcase a remarkable instance of parallel evolution toward complex multicellularity and macroscopic thalli in the Viridiplantae lineage. Within the green seaweeds, several Ulva species ("sea lettuce") are model organisms for studying carbon assimilation, interactions with bacteria, life cycle progression, and morphogenesis. Ulva species are also notorious for their fast growth and capacity to dominate nutrient-rich, anthropogenically disturbed coastal ecosystems during "green tide" blooms. From an economic perspective, Ulva has garnered increasing attention as a promising feedstock for the production of food, feed, and biobased products, also as a means of removing excess nutrients from the environment. We propose that Ulva is poised to further develop as a model in green seaweed research. In this perspective, we focus explicitly on Ulva mutabilis/compressa as a model species and highlight the molecular data and tools that are currently available or in development. We discuss several areas that will benefit from future research or where exciting new developments have been reported in other Ulva species.}, } @article {pmid37256290, year = {2023}, author = {Jiang, P and Kreitman, M and Reinitz, J}, title = {The effect of mutational robustness on the evolvability of multicellular organisms and eukaryotic cells.}, journal = {Journal of evolutionary biology}, volume = {36}, number = {6}, pages = {906-924}, pmid = {37256290}, issn = {1420-9101}, support = {R01 OD010936/OD/NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; *Eukaryotic Cells ; Models, Genetic ; Mutation ; Phenotype ; }, abstract = {Canalization involves mutational robustness, the lack of phenotypic change as a result of genetic mutations. Given the large divergence in phenotype across species, understanding the relationship between high robustness and evolvability has been of interest to both theorists and experimentalists. Although canalization was originally proposed in the context of multicellular organisms, the effect of multicellularity and other classes of hierarchical organization on evolvability has not been considered by theoreticians. We address this issue using a Boolean population model with explicit representation of an environment in which individuals with explicit genotype and a hierarchical phenotype representing multicellularity evolve. Robustness is described by a single real number between zero and one which emerges from the genotype-phenotype map. We find that high robustness is favoured in constant environments, and lower robustness is favoured after environmental change. Multicellularity and hierarchical organization severely constrain robustness: peak evolvability occurs at an absolute level of robustness of about 0.99 compared with values of about 0.5 in a classical neutral network model. These constraints result in a sharp peak of evolvability in which the maximum is set by the fact that the fixation of adaptive mutations becomes more improbable as robustness decreases. When robustness is put under genetic control, robustness levels leading to maximum evolvability are selected for, but maximal relative fitness appears to require recombination.}, } @article {pmid37253212, year = {2023}, author = {Hoch, NC}, title = {Tissue Specificity of DNA Damage and Repair.}, journal = {Physiology (Bethesda, Md.)}, volume = {38}, number = {5}, pages = {0}, doi = {10.1152/physiol.00006.2023}, pmid = {37253212}, issn = {1548-9221}, mesh = {Humans ; Organ Specificity ; *DNA Damage ; *DNA Repair ; Aging/genetics ; DNA/genetics/metabolism ; }, abstract = {DNA is a remarkable biochemical macromolecule tasked with storing the genetic information that instructs life on planet Earth. However, its inherent chemical instability within the cellular milieu is incompatible with the accurate transmission of genetic information to subsequent generations. Therefore, biochemical pathways that continuously survey and repair DNA are essential to sustain life, and the fundamental mechanisms by which different DNA lesions are repaired have remained well conserved throughout evolution. Nonetheless, the emergence of multicellular organisms led to profound differences in cellular context and physiology, leading to large variations in the predominant sources of DNA damage between different cell types and in the relative contribution of different DNA repair pathways toward genome maintenance in different tissues. While we continue to make large strides into understanding how individual DNA repair mechanisms operate on a molecular level, much less attention is given to these cell type-specific differences. This short review aims to provide a broad overview of DNA damage and repair mechanisms to nonspecialists and to highlight some fundamental open questions in tissue and cell-type-specificity of these processes, which may have profound implications for our understanding of important pathophysiological processes such as cancer, neurodegeneration, and aging.}, } @article {pmid37247371, year = {2023}, author = {McCourt, RM and Lewis, LA and Strother, PK and Delwiche, CF and Wickett, NJ and de Vries, J and Bowman, JL}, title = {Green land: Multiple perspectives on green algal evolution and the earliest land plants.}, journal = {American journal of botany}, volume = {110}, number = {5}, pages = {e16175}, doi = {10.1002/ajb2.16175}, pmid = {37247371}, issn = {1537-2197}, mesh = {Biological Evolution ; Ecosystem ; *Embryophyta/genetics ; Phylogeny ; Plants/genetics ; *Chlorophyta/genetics ; Evolution, Molecular ; }, abstract = {Green plants, broadly defined as green algae and the land plants (together, Viridiplantae), constitute the primary eukaryotic lineage that successfully colonized Earth's emergent landscape. Members of various clades of green plants have independently made the transition from fully aquatic to subaerial habitats many times throughout Earth's history. The transition, from unicells or simple filaments to complex multicellular plant bodies with functionally differentiated tissues and organs, was accompanied by innovations built upon a genetic and phenotypic toolkit that have served aquatic green phototrophs successfully for at least a billion years. These innovations opened an enormous array of new, drier places to live on the planet and resulted in a huge diversity of land plants that have dominated terrestrial ecosystems over the past 500 million years. This review examines the greening of the land from several perspectives, from paleontology to phylogenomics, to water stress responses and the genetic toolkit shared by green algae and plants, to the genomic evolution of the sporophyte generation. We summarize advances on disparate fronts in elucidating this important event in the evolution of the biosphere and the lacunae in our understanding of it. We present the process not as a step-by-step advancement from primitive green cells to an inevitable success of embryophytes, but rather as a process of adaptations and exaptations that allowed multiple clades of green plants, with various combinations of morphological and physiological terrestrialized traits, to become diverse and successful inhabitants of the land habitats of Earth.}, } @article {pmid37239953, year = {2023}, author = {Kozlov, AP}, title = {Carcino-Evo-Devo, A Theory of the Evolutionary Role of Hereditary Tumors.}, journal = {International journal of molecular sciences}, volume = {24}, number = {10}, pages = {}, pmid = {37239953}, issn = {1422-0067}, support = {The strategic academic leadership program 'Priority 2030' (Agreement 075-15-2021-1333 dated 30 September 2021)//Ministry of Science and Higher Education of the Russian Federation/ ; }, mesh = {*Biological Evolution ; *Developmental Biology ; }, abstract = {A theory of the evolutionary role of hereditary tumors, or the carcino-evo-devo theory, is being developed. The main hypothesis of the theory, the hypothesis of evolution by tumor neofunctionalization, posits that hereditary tumors provided additional cell masses during the evolution of multicellular organisms for the expression of evolutionarily novel genes. The carcino-evo-devo theory has formulated several nontrivial predictions that have been confirmed in the laboratory of the author. It also suggests several nontrivial explanations of biological phenomena previously unexplained by the existing theories or incompletely understood. By considering three major types of biological development-individual, evolutionary, and neoplastic development-within one theoretical framework, the carcino-evo-devo theory has the potential to become a unifying biological theory.}, } @article {pmid37233789, year = {2023}, author = {Wu, N and Wei, L and Zhu, Z and Liu, Q and Li, K and Mao, F and Qiao, J and Zhao, X}, title = {Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction.}, journal = {Protein & cell}, volume = {}, number = {}, pages = {}, doi = {10.1093/procel/pwad032}, pmid = {37233789}, issn = {1674-8018}, abstract = {Originating but free from chromosomal DNA, extrachromosomal circular DNAs (eccDNAs) are organized in circular form and have long been found in unicellular and multicellular eukaryotes. Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation-deletion-amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.}, } @article {pmid37232711, year = {2023}, author = {Wang, X and Zhang, Y and Xie, M and Wang, Z and Qiao, H}, title = {Temperature-Promoted Giant Unilamellar Vesicle (GUV) Aggregation: A Way of Multicellular Formation.}, journal = {Current issues in molecular biology}, volume = {45}, number = {5}, pages = {3757-3771}, pmid = {37232711}, issn = {1467-3045}, support = {Grant No. cstc2021jcyj-msxmX0550//General Project of Chongqing Natural Science Foundation/ ; }, abstract = {The evolution of unicellular to multicellular life is considered to be an important step in the origin of life, and it is crucial to study the influence of environmental factors on this process through cell models in the laboratory. In this paper, we used giant unilamellar vesicles (GUVs) as a cell model to investigate the relationship between environmental temperature changes and the evolution of unicellular to multicellular life. The zeta potential of GUVs and the conformation of the headgroup of phospholipid molecules at different temperatures were examined using phase analysis light scattering (PALS) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), respectively. In addition, the effect of increasing temperature on the aggregation of GUVs was further investigated in ionic solutions, and the possible mechanisms involved were explored. The results showed that increasing temperature reduced the repulsive forces between cells models and promoted their aggregation. This study could effectively contribute to our understanding of the evolution of primitive unicellular to multicellular life.}, } @article {pmid37223732, year = {2023}, author = {Hengge, R and Pruteanu, M and Stülke, J and Tschowri, N and Turgay, K}, title = {Recent advances and perspectives in nucleotide second messenger signaling in bacteria.}, journal = {microLife}, volume = {4}, number = {}, pages = {uqad015}, pmid = {37223732}, issn = {2633-6693}, abstract = {Nucleotide second messengers act as intracellular 'secondary' signals that represent environmental or cellular cues, i.e. the 'primary' signals. As such, they are linking sensory input with regulatory output in all living cells. The amazing physiological versatility, the mechanistic diversity of second messenger synthesis, degradation, and action as well as the high level of integration of second messenger pathways and networks in prokaryotes has only recently become apparent. In these networks, specific second messengers play conserved general roles. Thus, (p)ppGpp coordinates growth and survival in response to nutrient availability and various stresses, while c-di-GMP is the nucleotide signaling molecule to orchestrate bacterial adhesion and multicellularity. c-di-AMP links osmotic balance and metabolism and that it does so even in Archaea may suggest a very early evolutionary origin of second messenger signaling. Many of the enzymes that make or break second messengers show complex sensory domain architectures, which allow multisignal integration. The multiplicity of c-di-GMP-related enzymes in many species has led to the discovery that bacterial cells are even able to use the same freely diffusible second messenger in local signaling pathways that can act in parallel without cross-talking. On the other hand, signaling pathways operating with different nucleotides can intersect in elaborate signaling networks. Apart from the small number of common signaling nucleotides that bacteria use for controlling their cellular "business," diverse nucleotides were recently found to play very specific roles in phage defense. Furthermore, these systems represent the phylogenetic ancestors of cyclic nucleotide-activated immune signaling in eukaryotes.}, } @article {pmid37220133, year = {2023}, author = {Lipińska-Zubrycka, L and Grochowski, M and Bähler, J and Małecki, M}, title = {Pervasive mRNA uridylation in fission yeast is catalysed by both Cid1 and Cid16 terminal uridyltransferases.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0285576}, pmid = {37220133}, issn = {1932-6203}, support = {095598/Z/11/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {RNA, Messenger ; *Schizosaccharomyces ; Saccharomyces cerevisiae ; RNA ; Catalysis ; UDPglucose-Hexose-1-Phosphate Uridylyltransferase ; Nucleotidyltransferases ; *Schizosaccharomyces pombe Proteins ; }, abstract = {Messenger RNA uridylation is pervasive and conserved among eukaryotes, but the consequences of this modification for mRNA fate are still under debate. Utilising a simple model organism to study uridylation may facilitate efforts to understand the cellular function of this process. Here we demonstrate that uridylation can be detected using simple bioinformatics approach. We utilise it to unravel widespread transcript uridylation in fission yeast and demonstrate the contribution of both Cid1 and Cid16, the only two annotated terminal uridyltransferases (TUT-ases) in this yeast. To detect uridylation in transcriptome data, we used a RNA-sequencing (RNA-seq) library preparation protocol involving initial linker ligation to fragmented RNA-an approach borrowed from small RNA sequencing that was commonly used in older RNA-seq protocols. We next explored the data to detect uridylation marks. Our analysis show that uridylation in yeast is pervasive, similarly to the one in multicellular organisms. Importantly, our results confirm the role of the cytoplasmic uridyltransferase Cid1 as the primary uridylation catalyst. However, we also observed an auxiliary role of the second uridyltransferase, Cid16. Thus both fission yeast uridyltransferases are involved in mRNA uridylation. Intriguingly, we found no physiological phenotype of the single and double deletion mutants of cid1 and cid16 and only minimal impact of uridylation on steady-state mRNA levels. Our work establishes fission yeast as a potent model to study uridylation in a simple eukaryote, and we demonstrate that it is possible to detect uridylation marks in RNA-seq data without the need for specific methodologies.}, } @article {pmid37219671, year = {2023}, author = {Gmiter, D and Pacak, I and Nawrot, S and Czerwonka, G and Kaca, W}, title = {Genomes comparison of two Proteus mirabilis clones showing varied swarming ability.}, journal = {Molecular biology reports}, volume = {50}, number = {7}, pages = {5817-5826}, pmid = {37219671}, issn = {1573-4978}, support = {2019/33/N/NZ6/02406//Narodowym Centrum Nauki/ ; 2017/01/X/NZ6/01141//Narodowe Centrum Nauki/ ; }, mesh = {Humans ; Proteus mirabilis/genetics ; *Urinary Tract Infections/genetics/microbiology ; Clone Cells ; *Proteus Infections/microbiology ; }, abstract = {BACKGROUND: Proteus mirabilis is a Gram-negative bacteria most noted for its involvement with catheter-associated urinary tract infections. It is also known for its multicellular migration over solid surfaces, referred to as 'swarming motility'. Here we analyzed the genomic sequences of two P. mirabilis isolates, designated K38 and K39, which exhibit varied swarming ability.

METHODS AND RESULTS: The isolates genomes were sequenced using Illumina NextSeq sequencer, resulting in about 3.94 Mbp, with a GC content of 38.6%, genomes. Genomes were subjected for in silico comparative investigation. We revealed that, despite a difference in swarming motility, the isolates showed high genomic relatedness (up to 100% ANI similarity), suggesting that one of the isolates probably originated from the other.

CONCLUSIONS: The genomic sequences will allow us to investigate the mechanism driving this intriguing phenotypic heterogeneity between closely related P. mirabilis isolates. Phenotypic heterogeneity is an adaptive strategy of bacterial cells to several environmental pressures. It is also an important factor related to their pathogenesis. Therefore, the availability of these genomic sequences will facilitate studies that focus on the host-pathogen interactions during catheter-associated urinary tract infections.}, } @article {pmid37211257, year = {2023}, author = {Fields, C and Levin, M}, title = {Regulative development as a model for origin of life and artificial life studies.}, journal = {Bio Systems}, volume = {229}, number = {}, pages = {104927}, doi = {10.1016/j.biosystems.2023.104927}, pmid = {37211257}, issn = {1872-8324}, mesh = {Humans ; *Artificial Life ; Thermodynamics ; }, abstract = {Using the formal framework of the Free Energy Principle, we show how generic thermodynamic requirements on bidirectional information exchange between a system and its environment can generate complexity. This leads to the emergence of hierarchical computational architectures in systems that operate sufficiently far from thermal equilibrium. In this setting, the environment of any system increases its ability to predict system behavior by "engineering" the system towards increased morphological complexity and hence larger-scale, more macroscopic behaviors. When seen in this light, regulative development becomes an environmentally-driven process in which "parts" are assembled to produce a system with predictable behavior. We suggest on this basis that life is thermodynamically favorable and that, when designing artificial living systems, human engineers are acting like a generic "environment".}, } @article {pmid37205856, year = {2023}, author = {Hu, K and Le Vo, KL and Wang, F and Zhang, X and Gu, C and Fang, N and Phan, NTN and Ewing, AG}, title = {Single Exosome Amperometric Measurements Reveal Encapsulation of Chemical Messengers for Intercellular Communication.}, journal = {Journal of the American Chemical Society}, volume = {145}, number = {21}, pages = {11499-11503}, doi = {10.1021/jacs.3c02844}, pmid = {37205856}, issn = {1520-5126}, mesh = {*Exosomes/metabolism ; *Extracellular Vesicles/metabolism ; Cell Communication ; Cell Membrane/metabolism ; Neurons ; }, abstract = {In multicellular organisms, cells typically communicate by sending and receiving chemical signals. Chemical messengers involved in the exocytosis of neuroendocrine cells or neurons are generally assumed to only originate from the fusing of intracellular large dense core vesicles (LDCVs) or synaptic vesicles with the cellular membrane following stimulation. Accumulated evidence suggests that exosomes─one of the main extracellular vesicles (EVs)─carrying cell-dependent DNA, mRNA, proteins, etc., play an essential role in cellular communication. Due to experimental limitations, it has been difficult to monitor the real-time release of individual exosomes; this restricts a comprehensive understanding of the basic molecular mechanisms and the functions of exosomes. In this work, we introduce amperometry with microelectrodes to capture the dynamic release of single exosomes from a single living cell, distinguish them from other EVs, and differentiate the molecules inside exosomes and those secreted from LDCVs. We show that, similar to many LDCVs and synaptic vesicles, exosomes released by neuroendocrine cells also contain catecholamine transmitters. This finding reveals a different mode of chemical communication via exosome-encapsulated chemical messengers and a potential interconnection between the two release pathways, changing the canonical view of exocytosis of neuroendocrine cells and possibly neurons. This defines a new mechanism for chemical communication at the fundamental level and opens new avenues in the research of the molecular biology of exosomes in the neuroendocrine and central nervous systems.}, } @article {pmid37202179, year = {2023}, author = {Sobala, ŁF}, title = {Evolution and phylogenetic distribution of endo-α-mannosidase.}, journal = {Glycobiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/glycob/cwad041}, pmid = {37202179}, issn = {1460-2423}, abstract = {While glycans underlie many biological processes, such as protein folding, cell adhesion and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. It is unique as the only endo-acting mannosidase found in this organelle. Relatively little is known about its origins and evolutionary history; so far it was reported to occur only in vertebrates. In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. The endomannosidase was found to be more widely distributed in animals and other eukaryotes. The protein motif changes in context of the canonical animal enzyme were tracked. Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. Finally, a framework where N-glycosylation co-evolved with complex multicellularity is described. A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. This systematic analysis of the endomannosidase evolution is one step towards this goal.}, } @article {pmid37195672, year = {2023}, author = {Fernandes, J}, title = {Virus-Induced Lysis of Tumor and Other Pathogenic Unicellular Entities and Its Potential to Treat Leishmaniasis.}, journal = {DNA and cell biology}, volume = {42}, number = {6}, pages = {305-314}, doi = {10.1089/dna.2023.0048}, pmid = {37195672}, issn = {1557-7430}, mesh = {Humans ; *Leishmaniasis/drug therapy/parasitology ; *Leishmania/metabolism ; Cell Death ; *Neoplasms ; Saccharomyces cerevisiae ; *Viruses ; }, abstract = {This article is focused on the main pathways used by viruses to achieve infection and lysis of unicellular eukaryotes described as pathogenic for multicellular organisms. In light of the recent discussions on how tumor cells exhibit unicellular behavior, highly malignant cells can be considered as another unicellular pathogenic entity, but with endogenous origin. Thus, a comparative panel of viral lysis of exogenous pathogenic unicellular eukaryotes such as Acanthamoeba sp., yeast, and tumors is presented. The important intracellular parasite Leishmania sp is also presented, which, in contrast, has its virulence improved by viral infections. The possible exploitation of viral-mediated eukaryotic cell lysis to overcome infections of Leishmania sp is discussed.}, } @article {pmid37183897, year = {2023}, author = {Kaucka, M}, title = {Cis-regulatory landscapes in the evolution and development of the mammalian skull.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1880}, pages = {20220079}, pmid = {37183897}, issn = {1471-2970}, mesh = {Animals ; *Evolution, Molecular ; *Mammals/genetics ; Gene Regulatory Networks ; Skull ; Head ; }, abstract = {Extensive morphological variation found in mammals reflects the wide spectrum of their ecological adaptations. The highest morphological diversity is present in the craniofacial region, where geometry is mainly dictated by the bony skull. Mammalian craniofacial development represents complex multistep processes governed by numerous conserved genes that require precise spatio-temporal control. A central question in contemporary evolutionary biology is how a defined set of conserved genes can orchestrate formation of fundamentally different structures, and therefore how morphological variability arises. In principle, differential gene expression patterns during development are the source of morphological variation. With the emergence of multicellular organisms, precise regulation of gene expression in time and space is attributed to cis-regulatory elements. These elements contribute to higher-order chromatin structure and together with trans-acting factors control transcriptional landscapes that underlie intricate morphogenetic processes. Consequently, divergence in cis-regulation is believed to rewire existing gene regulatory networks and form the core of morphological evolution. This review outlines the fundamental principles of the genetic code and genomic regulation interplay during development. Recent work that deepened our comprehension of cis-regulatory element origin, divergence and function is presented here to illustrate the state-of-the-art research that uncovered the principles of morphological novelty. This article is part of the theme issue 'The mammalian skull: development, structure and function'.}, } @article {pmid37176080, year = {2023}, author = {Suwannachuen, N and Leetanasaksakul, K and Roytrakul, S and Phaonakrop, N and Thaisakun, S and Roongsattham, P and Jantasuriyarat, C and Sanevas, N and Sirikhachornkit, A}, title = {Palmelloid Formation and Cell Aggregation Are Essential Mechanisms for High Light Tolerance in a Natural Strain of Chlamydomonas reinhardtii.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37176080}, issn = {1422-0067}, support = {This project is funded by National Research Council of Thailand (NRCT) and Kasetsart Univer-sity : N42A650287. This research and innovation activity is funded by National Research Council of Thailand (NRCT). This research is supported in part by the Grad//This project is funded by National Research Council of Thailand (NRCT) and Kasetsart Univer-sity : N42A650287. This research and innovation activity is funded by National Research Council of Thailand (NRCT). This research is supported in part by the Grad/ ; }, mesh = {*Chlamydomonas reinhardtii/metabolism ; Reactive Oxygen Species/metabolism ; Proteomics ; *Chlamydomonas/metabolism ; Photosynthesis/physiology ; }, abstract = {Photosynthetic organisms, such as higher plants and algae, require light to survive. However, an excessive amount of light can be harmful due to the production of reactive oxygen species (ROS), which cause cell damage and, if it is not effectively regulated, cell death. The study of plants' responses to light can aid in the development of methods to improve plants' growth and productivity. Due to the multicellular nature of plants, there may be variations in the results based on plant age and tissue type. Chlamydomonas reinhardtii, a unicellular green alga, has also been used as a model organism to study photosynthesis and photoprotection. Nonetheless, the majority of the research has been conducted with strains that have been consistently utilized in laboratories and originated from the same source. Despite the availability of many field isolates of this species, very few studies have compared the light responses of field isolates. This study examined the responses of two field isolates of Chlamydomonas to high light stress. The light-tolerant strain, CC-4414, managed reactive oxygen species (ROS) slightly better than the sensitive strain, CC-2344, did. The proteomic data of cells subjected to high light revealed cellular modifications of the light-tolerant strain toward membrane proteins. The morphology of cells under light stress revealed that this strain utilized the formation of palmelloid structures and cell aggregation to shield cells from excessive light. As indicated by proteome data, morphological modifications occur simultaneously with the increase in protein degradation and autophagy. By protecting cells from stress, cells are able to continue to upregulate ROS management mechanisms and prevent cell death. This is the first report of palmelloid formation in Chlamydomonas under high light stress.}, } @article {pmid37173684, year = {2023}, author = {Foo, YZ and Lagisz, M and O'Dea, RE and Nakagawa, S}, title = {The influence of immune challenges on the mean and variance in reproductive investment: a meta-analysis of the terminal investment hypothesis.}, journal = {BMC biology}, volume = {21}, number = {1}, pages = {107}, pmid = {37173684}, issn = {1741-7007}, mesh = {Animals ; *Reproduction/physiology ; }, abstract = {Finding the optimal balance between survival and reproduction is a central puzzle in life-history theory. The terminal investment hypothesis predicts that when individuals encounter a survival threat that compromises future reproductive potential, they will increase immediate reproductive investment to maximise fitness. Despite decades of research on the terminal investment hypothesis, findings remain mixed. We examined the terminal investment hypothesis with a meta-analysis of studies that measured reproductive investment of multicellular iteroparous animals after a non-lethal immune challenge. We had two main aims. The first was to investigate whether individuals, on average, increase reproductive investment in response to an immune threat, as predicted by the terminal investment hypothesis. We also examined whether such responses vary adaptively on factors associated with the amount of reproductive opportunities left (residual reproductive value) in the individuals, as predicted by the terminal investment hypothesis. The second was to provide a quantitative test of a novel prediction based on the dynamic threshold model: that an immune threat increases between-individual variance in reproductive investment. Our results provided some support for our hypotheses. Older individuals, who are expected to have lower residual reproductive values, showed stronger mean terminal investment response than younger individuals. In terms of variance, individuals showed a divergence in responses, leading to an increase in variance. This increase in variance was especially amplified in longer-living species, which was consistent with our prediction that individuals in longer-living species should respond with greater individual variation due to increased phenotypic plasticity. We find little statistical evidence of publication bias. Together, our results highlight the need for a more nuanced view on the terminal investment hypothesis and a greater focus on the factors that drive individual responses.}, } @article {pmid37165189, year = {2023}, author = {Bozdag, GO and Zamani-Dahaj, SA and Day, TC and Kahn, PC and Burnetti, AJ and Lac, DT and Tong, K and Conlin, PL and Balwani, AH and Dyer, EL and Yunker, PJ and Ratcliff, WC}, title = {De novo evolution of macroscopic multicellularity.}, journal = {Nature}, volume = {617}, number = {7962}, pages = {747-754}, pmid = {37165189}, issn = {1476-4687}, support = {R35 GM138354/GM/NIGMS NIH HHS/United States ; }, mesh = {*Acclimatization ; *Biological Evolution ; Models, Biological ; *Saccharomyces cerevisiae/cytology/metabolism ; Anaerobiosis ; Aerobiosis ; Oxygen/analysis/metabolism ; Cell Shape ; *Cell Aggregation/physiology ; }, abstract = {While early multicellular lineages necessarily started out as relatively simple groups of cells, little is known about how they became Darwinian entities capable of sustained multicellular evolution[1-3]. Here we investigate this with a multicellularity long-term evolution experiment, selecting for larger group size in the snowflake yeast (Saccharomyces cerevisiae) model system. Given the historical importance of oxygen limitation[4], our ongoing experiment consists of three metabolic treatments[5]-anaerobic, obligately aerobic and mixotrophic yeast. After 600 rounds of selection, snowflake yeast in the anaerobic treatment group evolved to be macroscopic, becoming around 2 × 10[4] times larger (approximately mm scale) and about 10[4]-fold more biophysically tough, while retaining a clonal multicellular life cycle. This occurred through biophysical adaptation-evolution of increasingly elongate cells that initially reduced the strain of cellular packing and then facilitated branch entanglements that enabled groups of cells to stay together even after many cellular bonds fracture. By contrast, snowflake yeast competing for low oxygen[5] remained microscopic, evolving to be only around sixfold larger, underscoring the critical role of oxygen levels in the evolution of multicellular size. Together, this research provides unique insights into an ongoing evolutionary transition in individuality, showing how simple groups of cells overcome fundamental biophysical limitations through gradual, yet sustained, multicellular evolution.}, } @article {pmid37160092, year = {2023}, author = {Conlin, PL and Ratcliff, WC}, title = {Evolution: Understanding the origins of facultative multicellular life cycles.}, journal = {Current biology : CB}, volume = {33}, number = {9}, pages = {R356-R358}, doi = {10.1016/j.cub.2023.03.065}, pmid = {37160092}, issn = {1879-0445}, mesh = {Animals ; *Life Cycle Stages ; *Saccharomyces cerevisiae ; }, abstract = {Multicellular organisms exhibit a fascinating diversity of life cycles, but little is known about the factors governing life-cycle evolution. New studies of wild yeast and cyanobacteria provide insight into how and why facultative multicellular life cycles arise.}, } @article {pmid37157910, year = {2023}, author = {Pradeu, T and Daignan-Fornier, B and Ewald, A and Germain, PL and Okasha, S and Plutynski, A and Benzekry, S and Bertolaso, M and Bissell, M and Brown, JS and Chin-Yee, B and Chin-Yee, I and Clevers, H and Cognet, L and Darrason, M and Farge, E and Feunteun, J and Galon, J and Giroux, E and Green, S and Gross, F and Jaulin, F and Knight, R and Laconi, E and Larmonier, N and Maley, C and Mantovani, A and Moreau, V and Nassoy, P and Rondeau, E and Santamaria, D and Sawai, CM and Seluanov, A and Sepich-Poore, GD and Sisirak, V and Solary, E and Yvonnet, S and Laplane, L}, title = {Reuniting philosophy and science to advance cancer research.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12971}, pmid = {37157910}, issn = {1469-185X}, support = {ANR-19-CE27-0027-01//Agence Nationale de la Recherche/ ; //SIRIC-Brio/ ; //Région Nouvelle Aquitaine/ ; GBMF9021//Gordon and Betty Moore Foundation/ ; 2021-1-EMERG-54-CNRS DR 5-1//Canceropôle Emergence/ ; //CNRS program/ ; EL2020//Ligue National Contre le Cancer Equipe labelisée/ ; }, abstract = {Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, and methodological framework. Without such a framework, oncology will collect piecemeal results, with scant dialogue between the different scientific communities studying cancer. We argue that one important way forward in service of a more successful dialogue is through greater integration of applied sciences (experimental and clinical) with conceptual and theoretical approaches, informed by philosophical methods. By way of illustration, we explore six central themes: (i) the role of mutations in cancer; (ii) the clonal evolution of cancer cells; (iii) the relationship between cancer and multicellularity; (iv) the tumour microenvironment; (v) the immune system; and (vi) stem cells. In each case, we examine open questions in the scientific literature through a philosophical methodology and show the benefit of such a synergy for the scientific and medical understanding of cancer.}, } @article {pmid37156924, year = {2023}, author = {Levin, M}, title = {Darwin's agential materials: evolutionary implications of multiscale competency in developmental biology.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {80}, number = {6}, pages = {142}, pmid = {37156924}, issn = {1420-9071}, support = {62212//John Templeton Foundation/ ; }, mesh = {*Biological Evolution ; Genotype ; *Genome ; Phenotype ; Developmental Biology ; }, abstract = {A critical aspect of evolution is the layer of developmental physiology that operates between the genotype and the anatomical phenotype. While much work has addressed the evolution of developmental mechanisms and the evolvability of specific genetic architectures with emergent complexity, one aspect has not been sufficiently explored: the implications of morphogenetic problem-solving competencies for the evolutionary process itself. The cells that evolution works with are not passive components: rather, they have numerous capabilities for behavior because they derive from ancestral unicellular organisms with rich repertoires. In multicellular organisms, these capabilities must be tamed, and can be exploited, by the evolutionary process. Specifically, biological structures have a multiscale competency architecture where cells, tissues, and organs exhibit regulative plasticity-the ability to adjust to perturbations such as external injury or internal modifications and still accomplish specific adaptive tasks across metabolic, transcriptional, physiological, and anatomical problem spaces. Here, I review examples illustrating how physiological circuits guiding cellular collective behavior impart computational properties to the agential material that serves as substrate for the evolutionary process. I then explore the ways in which the collective intelligence of cells during morphogenesis affect evolution, providing a new perspective on the evolutionary search process. This key feature of the physiological software of life helps explain the remarkable speed and robustness of biological evolution, and sheds new light on the relationship between genomes and functional anatomical phenotypes.}, } @article {pmid37155901, year = {2023}, author = {Cooney, DB and Levin, SA and Mori, Y and Plotkin, JB}, title = {Evolutionary dynamics within and among competing groups.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {20}, pages = {e2216186120}, pmid = {37155901}, issn = {1091-6490}, mesh = {Humans ; *Cooperative Behavior ; *Biological Evolution ; Selection, Genetic ; Game Theory ; }, abstract = {Biological and social systems are structured at multiple scales, and the incentives of individuals who interact in a group may diverge from the collective incentive of the group as a whole. Mechanisms to resolve this tension are responsible for profound transitions in evolutionary history, including the origin of cellular life, multicellular life, and even societies. Here, we synthesize a growing literature that extends evolutionary game theory to describe multilevel evolutionary dynamics, using nested birth-death processes and partial differential equations to model natural selection acting on competition within and among groups of individuals. We analyze how mechanisms known to promote cooperation within a single group-including assortment, reciprocity, and population structure-alter evolutionary outcomes in the presence of competition among groups. We find that population structures most conducive to cooperation in multiscale systems can differ from those most conducive within a single group. Likewise, for competitive interactions with a continuous range of strategies we find that among-group selection may fail to produce socially optimal outcomes, but it can nonetheless produce second-best solutions that balance individual incentives to defect with the collective incentives for cooperation. We conclude by describing the broad applicability of multiscale evolutionary models to problems ranging from the production of diffusible metabolites in microbes to the management of common-pool resources in human societies.}, } @article {pmid37153718, year = {2023}, author = {W B, M and A S, R and P, M and F, B}, title = {Cellular and Natural Viral Engineering in Cognition-Based Evolution.}, journal = {Communicative & integrative biology}, volume = {16}, number = {1}, pages = {2196145}, pmid = {37153718}, issn = {1942-0889}, abstract = {Neo-Darwinism conceptualizes evolution as the continuous succession of predominately random genetic variations disciplined by natural selection. In that frame, the primary interaction between cells and the virome is relegated to host-parasite dynamics governed by selective influences. Cognition-Based Evolution regards biological and evolutionary development as a reciprocating cognition-based informational interactome for the protection of self-referential cells. To sustain cellular homeorhesis, cognitive cells collaborate to assess the validity of ambiguous biological information. That collective interaction involves coordinate measurement, communication, and active deployment of resources as Natural Cellular Engineering. These coordinated activities drive multicellularity, biological development, and evolutionary change. The virome participates as the vital intercessory among the cellular domains to ensure their shared permanent perpetuation. The interactions between the virome and the cellular domains represent active virocellular cross-communications for the continual exchange of resources. Modular genetic transfers between viruses and cells carry bioactive potentials. Those exchanges are deployed as nonrandom flexible tools among the domains in their continuous confrontation with environmental stresses. This alternative framework fundamentally shifts our perspective on viral-cellular interactions, strengthening established principles of viral symbiogenesis. Pathogenesis can now be properly appraised as one expression of a range of outcomes between cells and viruses within a larger conceptual framework of Natural Viral Engineering as a co-engineering participant with cells. It is proposed that Natural Viral Engineering should be viewed as a co-existent facet of Natural Cellular Engineering within Cognition-Based Evolution.}, } @article {pmid37141807, year = {2023}, author = {Tsai, HH and Wang, J and Geldner, N and Zhou, F}, title = {Spatiotemporal control of root immune responses during microbial colonization.}, journal = {Current opinion in plant biology}, volume = {74}, number = {}, pages = {102369}, doi = {10.1016/j.pbi.2023.102369}, pmid = {37141807}, issn = {1879-0356}, abstract = {The entire evolutionary trajectory of plants towards large and complex multi-cellular organisms has been accompanied by incessant interactions with omnipresent unicellular microbes. This led to the evolution of highly complex microbial communities, whose members display the entire spectrum of pathogenic to mutualistic behaviors. Plant roots are dynamic, fractally growing organs and even small Arabidopsis roots harbor millions of individual microbes of diverse taxa. It is evident that microbes at different positions on a root surface could experience fundamentally different environments, which, moreover, rapidly change over time. Differences in spatial scales between microbes and roots compares to humans and the cities they inhabit. Such considerations make it evident that mechanisms of root-microbe interactions can only be understood if analyzed at relevant spatial and temporal scales. This review attempts to provide an overview of the rapid recent progress that has been made in mapping and manipulating plant damage and immune responses at cellular resolution, as well as in visualizing bacterial communities and their transcriptional activities. We further discuss the impact that such approaches will have for a more predictive understanding of root-microbe interactions.}, } @article {pmid37140022, year = {2023}, author = {Krasovec, M and Hoshino, M and Zheng, M and Lipinska, AP and Coelho, SM}, title = {Low Spontaneous Mutation Rate in Complex Multicellular Eukaryotes with a Haploid-Diploid Life Cycle.}, journal = {Molecular biology and evolution}, volume = {40}, number = {6}, pages = {}, pmid = {37140022}, issn = {1537-1719}, mesh = {Animals ; Haploidy ; *Diploidy ; Mutation Rate ; Eukaryota ; Life Cycle Stages/genetics ; Plants ; *Phaeophyta/genetics ; }, abstract = {The spontaneous mutation rate µ is a crucial parameter to understand evolution and biodiversity. Mutation rates are highly variable across species, suggesting that µ is susceptible to selection and drift and that species life cycle and life history may impact its evolution. In particular, asexual reproduction and haploid selection are expected to affect the mutation rate, but very little empirical data are available to test this expectation. Here, we sequence 30 genomes of a parent-offspring pedigree in the model brown alga Ectocarpus sp.7, and 137 genomes of an interspecific cross of the closely related brown alga Scytosiphon to have access to the spontaneous mutation rate of representative organisms of a complex multicellular eukaryotic lineage outside animals and plants, and to evaluate the potential impact of life cycle on the mutation rate. Brown algae alternate between a haploid and a diploid stage, both multicellular and free living, and utilize both sexual and asexual reproduction. They are, therefore, excellent models to empirically test expectations of the effect of asexual reproduction and haploid selection on mutation rate evolution. We estimate that Ectocarpus has a base substitution rate of µbs = 4.07 × 10-10 per site per generation, whereas the Scytosiphon interspecific cross had µbs = 1.22 × 10-9. Overall, our estimations suggest that these brown algae, despite being multicellular complex eukaryotes, have unusually low mutation rates. In Ectocarpus, effective population size (Ne) could not entirely explain the low µbs. We propose that the haploid-diploid life cycle, combined with extensive asexual reproduction, may be additional key drivers of the mutation rate in these organisms.}, } @article {pmid37123368, year = {2023}, author = {Nikitin, MA and Romanova, DY and Borman, SI and Moroz, LL}, title = {Amino acids integrate behaviors in nerveless placozoans.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1125624}, pmid = {37123368}, issn = {1662-4548}, abstract = {Placozoans are the simplest known free-living animals without recognized neurons and muscles but a complex behavioral repertoire. However, mechanisms and cellular bases of behavioral coordination are unknown. Here, using Trichoplax adhaerens as a model, we described 0.02-0.002 Hz oscillations in locomotory and feeding patterns as evidence of complex multicellular integration; and showed their dependence on the endogenous secretion of signal molecules. Evolutionary conserved low-molecular-weight transmitters (glutamate, aspartate, glycine, GABA, and ATP) acted as coordinators of distinct locomotory and feeding patterns. Specifically, L-glutamate induced and partially mimicked endogenous feeding cycles, whereas glycine and GABA suppressed feeding. ATP-modified feeding is complex, first causing feeding-like cycles and then suppressing feeding. Trichoplax locomotion was modulated by glycine, GABA, and, surprisingly, by animals' own mucus trails. Mucus triples locomotory speed compared to clean substrates. Glycine and GABA increased the frequency of turns. The effects of the amino acids are likely mediated by numerous receptors (R), including those from ionotropic GluRs, metabotropic GluRs, and GABA-BR families. Eighty-five of these receptors are encoded in the Trichoplax genome, more than in any other animal sequenced. Phylogenetic reconstructions illuminate massive lineage-specific expansions of amino acid receptors in Placozoa, Cnidaria, and Porifera and parallel evolution of nutritional sensing. Furthermore, we view the integration of feeding behaviors in nerveless animals by amino acids as ancestral exaptations that pave the way for co-options of glutamate, glycine, GABA, and ATP as classical neurotransmitters in eumetazoans.}, } @article {pmid37107699, year = {2023}, author = {Grochau-Wright, ZI and Nedelcu, AM and Michod, RE}, title = {The Genetics of Fitness Reorganization during the Transition to Multicellularity: The Volvocine regA-like Family as a Model.}, journal = {Genes}, volume = {14}, number = {4}, pages = {}, pmid = {37107699}, issn = {2073-4425}, mesh = {Phylogeny ; *Chlorophyta ; *Volvox/genetics ; Models, Biological ; Cell Differentiation/genetics ; }, abstract = {The evolutionary transition from single-celled to multicellular individuality requires organismal fitness to shift from the cell level to a cell group. This reorganization of fitness occurs by re-allocating the two components of fitness, survival and reproduction, between two specialized cell types in the multicellular group: soma and germ, respectively. How does the genetic basis for such fitness reorganization evolve? One possible mechanism is the co-option of life history genes present in the unicellular ancestors of a multicellular lineage. For instance, single-celled organisms must regulate their investment in survival and reproduction in response to environmental changes, particularly decreasing reproduction to ensure survival under stress. Such stress response life history genes can provide the genetic basis for the evolution of cellular differentiation in multicellular lineages. The regA-like gene family in the volvocine green algal lineage provides an excellent model system to study how this co-option can occur. We discuss the origin and evolution of the volvocine regA-like gene family, including regA-the gene that controls somatic cell development in the model organism Volvox carteri. We hypothesize that the co-option of life history trade-off genes is a general mechanism involved in the transition to multicellular individuality, making volvocine algae and the regA-like family a useful template for similar investigations in other lineages.}, } @article {pmid37107559, year = {2023}, author = {Casotti, MC and Meira, DD and Zetum, ASS and Araújo, BC and Silva, DRCD and Santos, EVWD and Garcia, FM and Paula, F and Santana, GM and Louro, LS and Alves, LNR and Braga, RFR and Trabach, RSDR and Bernardes, SS and Louro, TES and Chiela, ECF and Lenz, G and Carvalho, EF and Louro, ID}, title = {Computational Biology Helps Understand How Polyploid Giant Cancer Cells Drive Tumor Success.}, journal = {Genes}, volume = {14}, number = {4}, pages = {}, pmid = {37107559}, issn = {2073-4425}, mesh = {Humans ; Cell Line, Tumor ; *Neoplasm Recurrence, Local/pathology ; *Giant Cells/metabolism/pathology ; Polyploidy ; Computational Biology ; }, abstract = {Precision and organization govern the cell cycle, ensuring normal proliferation. However, some cells may undergo abnormal cell divisions (neosis) or variations of mitotic cycles (endopolyploidy). Consequently, the formation of polyploid giant cancer cells (PGCCs), critical for tumor survival, resistance, and immortalization, can occur. Newly formed cells end up accessing numerous multicellular and unicellular programs that enable metastasis, drug resistance, tumor recurrence, and self-renewal or diverse clone formation. An integrative literature review was carried out, searching articles in several sites, including: PUBMED, NCBI-PMC, and Google Academic, published in English, indexed in referenced databases and without a publication time filter, but prioritizing articles from the last 3 years, to answer the following questions: (i) "What is the current knowledge about polyploidy in tumors?"; (ii) "What are the applications of computational studies for the understanding of cancer polyploidy?"; and (iii) "How do PGCCs contribute to tumorigenesis?"}, } @article {pmid37098330, year = {2023}, author = {Colgren, J and Burkhardt, P}, title = {Evolution: Was the nuclear-to-cytoplasmic ratio a key factor in the origin of animal multicellularity?.}, journal = {Current biology : CB}, volume = {33}, number = {8}, pages = {R298-R300}, doi = {10.1016/j.cub.2023.03.010}, pmid = {37098330}, issn = {1879-0445}, mesh = {Animals ; *Eukaryota ; *Mesomycetozoea ; Cytoplasm ; Cytosol ; Biological Evolution ; }, abstract = {The ichthyosporean Sphaeroforma arctica, a protist closely related to animals, displays coenocytic development followed by cellularization and cell release. A new study reveals that the nuclear-to-cytoplasmic ratio drives cellularization in these fascinating organisms.}, } @article {pmid37096591, year = {2023}, author = {Stéger, A and Palmgren, M}, title = {Hypothesis paper: the development of a regulatory layer in P2B autoinhibited Ca[2+]-ATPases may have facilitated plant terrestrialization and animal multicellularization.}, journal = {Plant signaling & behavior}, volume = {18}, number = {1}, pages = {2204284}, pmid = {37096591}, issn = {1559-2324}, mesh = {Animals ; *Adenosine Triphosphatases ; *Calmodulin/metabolism ; Protein Binding ; Calcium Signaling ; Calcium/metabolism ; }, abstract = {With the appearance of plants and animals, new challenges emerged. These multicellular eukaryotes had to solve for example the difficulties of multifaceted communication between cells and adaptation to new habitats. In this paper, we are looking for one piece of the puzzle that made the development of complex multicellular eukaryotes possible with a focus on regulation of P2B autoinhibited Ca[2+]-ATPases. P2B ATPases pump Ca[2+] out of the cytosol at the expense of ATP hydrolysis, and thereby maintain a steep gradient between the extra- and intracytosolic compartments which is utilized for Ca[2+]-mediated rapid cell signaling. The activity of these enzymes is regulated by a calmodulin (CaM)-responsive autoinhibitory region, which can be located in either termini of the protein, at the C-terminus in animals and at the N-terminus in plants. When the cytoplasmic Ca[2+] level reaches a threshold, the CaM/Ca[2+] complex binds to a calmodulin-binding domain (CaMBD) in the autoinhibitor, which leads to the upregulation of pump activity. In animals, protein activity is also controlled by acidic phospholipids that bind to a cytosolic portion of the pump. Here, we analyze the appearance of CaMBDs and the phospholipid-activating sequence and show that their evolution in animals and plants was independent. Furthermore, we hypothesize that different causes may have initiated the appearance of these regulatory layers: in animals, it is linked to the appearance of multicellularity, while in plants it co-occurs with their water-to-land transition.}, } @article {pmid37094139, year = {2023}, author = {Ros-Rocher, N and Kidner, RQ and Gerdt, C and Davidson, WS and Ruiz-Trillo, I and Gerdt, JP}, title = {Chemical factors induce aggregative multicellularity in a close unicellular relative of animals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {18}, pages = {e2216668120}, pmid = {37094139}, issn = {1091-6490}, support = {R35 GM138376/GM/NIGMS NIH HHS/United States ; T32 GM131994/GM/NIGMS NIH HHS/United States ; S10 OD024988/OD/NIH HHS/United States ; }, mesh = {Animals ; *Eukaryota/genetics ; *Biological Evolution ; Phylogeny ; }, abstract = {Regulated cellular aggregation is an essential process for development and healing in many animal tissues. In some animals and a few distantly related unicellular species, cellular aggregation is regulated by diffusible chemical cues. However, it is unclear whether regulated cellular aggregation was part of the life cycles of the first multicellular animals and/or their unicellular ancestors. To fill this gap, we investigated the triggers of cellular aggregation in one of animals' closest unicellular living relatives-the filasterean Capsaspora owczarzaki. We discovered that Capsaspora aggregation is induced by chemical cues, as observed in some of the earliest branching animals and other unicellular species. Specifically, we found that calcium ions and lipids present in lipoproteins function together to induce aggregation of viable Capsaspora cells. We also found that this multicellular stage is reversible as depletion of the cues triggers disaggregation, which can be overcome upon reinduction. Our finding demonstrates that chemically regulated aggregation is important across diverse members of the holozoan clade. Therefore, this phenotype was plausibly integral to the life cycles of the unicellular ancestors of animals.}, } @article {pmid37093889, year = {2023}, author = {Kumar, T and Sethuraman, R and Mitra, S and Ravindran, B and Narayanan, M}, title = {MultiCens: Multilayer network centrality measures to uncover molecular mediators of tissue-tissue communication.}, journal = {PLoS computational biology}, volume = {19}, number = {4}, pages = {e1011022}, pmid = {37093889}, issn = {1553-7358}, mesh = {Humans ; *Brain ; Gene Regulatory Networks/genetics ; *Alzheimer Disease/genetics ; }, abstract = {With the evolution of multicellularity, communication among cells in different tissues and organs became pivotal to life. Molecular basis of such communication has long been studied, but genome-wide screens for genes and other biomolecules mediating tissue-tissue signaling are lacking. To systematically identify inter-tissue mediators, we present a novel computational approach MultiCens (Multilayer/Multi-tissue network Centrality measures). Unlike single-layer network methods, MultiCens can distinguish within- vs. across-layer connectivity to quantify the "influence" of any gene in a tissue on a query set of genes of interest in another tissue. MultiCens enjoys theoretical guarantees on convergence and decomposability, and performs well on synthetic benchmarks. On human multi-tissue datasets, MultiCens predicts known and novel genes linked to hormones. MultiCens further reveals shifts in gene network architecture among four brain regions in Alzheimer's disease. MultiCens-prioritized hypotheses from these two diverse applications, and potential future ones like "Multi-tissue-expanded Gene Ontology" analysis, can enable whole-body yet molecular-level systems investigations in humans.}, } @article {pmid37086724, year = {2023}, author = {Hashimoto, A and Kawamura, N and Tarusawa, E and Takeda, I and Aoyama, Y and Ohno, N and Inoue, M and Kagamiuchi, M and Kato, D and Matsumoto, M and Hasegawa, Y and Nabekura, J and Schaefer, A and Moorhouse, AJ and Yagi, T and Wake, H}, title = {Microglia enable cross-modal plasticity by removing inhibitory synapses.}, journal = {Cell reports}, volume = {42}, number = {5}, pages = {112383}, doi = {10.1016/j.celrep.2023.112383}, pmid = {37086724}, issn = {2211-1247}, mesh = {Animals ; *Microglia ; Neurons/physiology ; Synapses/physiology ; Pyramidal Cells ; *Visual Cortex/physiology ; Neuronal Plasticity/physiology ; Vibrissae/physiology ; Somatosensory Cortex/physiology ; }, abstract = {Cross-modal plasticity is the repurposing of brain regions associated with deprived sensory inputs to improve the capacity of other sensory modalities. The functional mechanisms of cross-modal plasticity can indicate how the brain recovers from various forms of injury and how different sensory modalities are integrated. Here, we demonstrate that rewiring of the microglia-mediated local circuit synapse is crucial for cross-modal plasticity induced by visual deprivation (monocular deprivation [MD]). MD relieves the usual inhibition of functional connectivity between the somatosensory cortex and secondary lateral visual cortex (V2L). This results in enhanced excitatory responses in V2L neurons during whisker stimulation and a greater capacity for vibrissae sensory discrimination. The enhanced cross-modal response is mediated by selective removal of inhibitory synapse terminals on pyramidal neurons by the microglia in the V2L via matrix metalloproteinase 9 signaling. Our results provide insights into how cortical circuits integrate different inputs to functionally compensate for neuronal damage.}, } @article {pmid37083675, year = {2023}, author = {Isaksson, H and Brännström, Å and Libby, E}, title = {Minor variations in multicellular life cycles have major effects on adaptation.}, journal = {PLoS computational biology}, volume = {19}, number = {4}, pages = {e1010698}, pmid = {37083675}, issn = {1553-7358}, mesh = {Animals ; *Life Cycle Stages ; *Models, Theoretical ; Biological Evolution ; Acclimatization ; Phenotype ; }, abstract = {Multicellularity has evolved several independent times over the past hundreds of millions of years and given rise to a wide diversity of complex life. Recent studies have found that large differences in the fundamental structure of early multicellular life cycles can affect fitness and influence multicellular adaptation. Yet, there is an underlying assumption that at some scale or categorization multicellular life cycles are similar in terms of their adaptive potential. Here, we consider this possibility by exploring adaptation in a class of simple multicellular life cycles of filamentous organisms that only differ in one respect, how many daughter filaments are produced. We use mathematical models and evolutionary simulations to show that despite the similarities, qualitatively different mutations fix. In particular, we find that mutations with a tradeoff between cell growth and group survival, i.e. "selfish" or "altruistic" traits, spread differently. Specifically, altruistic mutations more readily spread in life cycles that produce few daughters while in life cycles producing many daughters either type of mutation can spread depending on the environment. Our results show that subtle changes in multicellular life cycles can fundamentally alter adaptation.}, } @article {pmid37081145, year = {2023}, author = {Cornwallis, CK and Svensson-Coelho, M and Lindh, M and Li, Q and Stábile, F and Hansson, LA and Rengefors, K}, title = {Single-cell adaptations shape evolutionary transitions to multicellularity in green algae.}, journal = {Nature ecology & evolution}, volume = {7}, number = {6}, pages = {889-902}, pmid = {37081145}, issn = {2397-334X}, support = {2018.0138//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 60501//John Templeton Foundation (JTF)/ ; 20210788//Crafoordska Stiftelsen (Crafoord Foundation)/ ; 2022-03503//Vetenskapsrådet (Swedish Research Council)/ ; 2016-03552//Vetenskapsrådet (Swedish Research Council)/ ; }, mesh = {Animals ; *Biological Evolution ; *Chlorophyta ; Acclimatization ; Predatory Behavior ; }, abstract = {The evolution of multicellular life has played a pivotal role in shaping biological diversity. However, we know surprisingly little about the natural environmental conditions that favour the formation of multicellular groups. Here we experimentally examine how key environmental factors (predation, nitrogen and water turbulence) combine to influence multicellular group formation in 35 wild unicellular green algae strains (19 Chlorophyta species). All environmental factors induced the formation of multicellular groups (more than four cells), but there was no evidence this was adaptive, as multicellularity (% cells in groups) was not related to population growth rate under any condition. Instead, population growth was related to extracellular matrix (ECM) around single cells and palmelloid formation, a unicellular life-cycle stage where two to four cells are retained within a mother-cell wall after mitosis. ECM production increased with nitrogen levels resulting in more cells being in palmelloids and higher rates of multicellular group formation. Examining the distribution of 332 algae species across 478 lakes monitored over 55 years, showed that ECM and nitrogen availability also predicted patterns of obligate multicellularity in nature. Our results highlight that adaptations of unicellular organisms to cope with environmental challenges may be key to understanding evolutionary routes to multicellular life.}, } @article {pmid37080197, year = {2023}, author = {Cadart, C and Bartz, J and Oaks, G and Liu, MZ and Heald, R}, title = {Polyploidy in Xenopus lowers metabolic rate by decreasing total cell surface area.}, journal = {Current biology : CB}, volume = {33}, number = {9}, pages = {1744-1752.e7}, pmid = {37080197}, issn = {1879-0445}, support = {R35 GM118183/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Triploidy ; Xenopus laevis/genetics ; *Polyploidy ; Ploidies ; Diploidy ; Cell Membrane ; }, abstract = {Although polyploidization is frequent in development, cancer, and evolution, impacts on animal metabolism are poorly understood. In Xenopus frogs, the number of genome copies (ploidy) varies across species and can be manipulated within a species. Here, we show that triploid tadpoles contain fewer, larger cells than diploids and consume oxygen at a lower rate. Drug treatments revealed that the major processes accounting for tadpole energy expenditure include cell proliferation, biosynthesis, and maintenance of plasma membrane potential. While inhibiting cell proliferation did not abolish the oxygen consumption difference between diploids and triploids, treatments that altered cellular biosynthesis or electrical potential did. Combining these results with a simple mathematical framework, we propose that the decrease in total cell surface area lowered production and activity of plasma membrane components including the Na[+]/K[+] ATPase, reducing energy consumption in triploids. Comparison of Xenopus species that evolved through polyploidization revealed that metabolic differences emerged during development when cell size scaled with genome size. Thus, ploidy affects metabolism by altering the cell surface area to volume ratio in a multicellular organism.}, } @article {pmid37068309, year = {2023}, author = {Xiao, K and Wang, Y and Dong, K and Zhang, S}, title = {SmartGate is a spatial metabolomics tool for resolving tissue structures.}, journal = {Briefings in bioinformatics}, volume = {24}, number = {3}, pages = {}, doi = {10.1093/bib/bbad141}, pmid = {37068309}, issn = {1477-4054}, mesh = {*Artificial Intelligence ; *Metabolomics/methods ; Biomarkers ; }, abstract = {Imaging mass spectrometry (IMS) is one of the powerful tools in spatial metabolomics for obtaining metabolite data and probing the internal microenvironment of organisms. It has dramatically advanced the understanding of the structure of biological tissues and the drug treatment of diseases. However, the complexity of IMS data hinders the further acquisition of biomarkers and the study of certain specific activities of organisms. To this end, we introduce an artificial intelligence tool, SmartGate, to enable automatic peak selection and spatial structure identification in an iterative manner. SmartGate selects discriminative m/z features from the previous iteration by differential analysis and employs a graph attention autoencoder model to perform spatial clustering for tissue segmentation using the selected features. We applied SmartGate to diverse IMS data at multicellular or subcellular spatial resolutions and compared it with four competing methods to demonstrate its effectiveness. SmartGate can significantly improve the accuracy of spatial segmentation and identify biomarker metabolites based on tissue structure-guided differential analysis. For multiple consecutive IMS data, SmartGate can effectively identify structures with spatial heterogeneity by introducing three-dimensional spatial neighbor information.}, } @article {pmid37067637, year = {2023}, author = {Ros-Rocher, N and Brunet, T}, title = {What is it like to be a choanoflagellate? Sensation, processing and behavior in the closest unicellular relatives of animals.}, journal = {Animal cognition}, volume = {}, number = {}, pages = {}, pmid = {37067637}, issn = {1435-9456}, support = {EvoMorphoCell 101040745/ERC_/European Research Council/International ; }, abstract = {All animals evolved from a single lineage of unicellular precursors more than 600 million years ago. Thus, the biological and genetic foundations for animal sensation, cognition and behavior must necessarily have arisen by modifications of pre-existing features in their unicellular ancestors. Given that the single-celled ancestors of the animal kingdom are extinct, the only way to reconstruct how these features evolved is by comparing the biology and genomic content of extant animals to their closest living relatives. Here, we reconstruct the Umwelt (the subjective, perceptive world) inhabited by choanoflagellates, a group of unicellular (or facultatively multicellular) aquatic microeukaryotes that are the closest living relatives of animals. Although behavioral research on choanoflagellates remains patchy, existing evidence shows that they are capable of chemosensation, photosensation and mechanosensation. These processes often involve specialized sensorimotor cellular appendages (cilia, microvilli, and/or filopodia) that resemble those that underlie perception in most animal sensory cells. Furthermore, comparative genomics predicts an extensive "sensory molecular toolkit" in choanoflagellates, which both provides a potential basis for known behaviors and suggests the existence of a largely undescribed behavioral complexity that presents exciting avenues for future research. Finally, we discuss how facultative multicellularity in choanoflagellates might help us understand how evolution displaced the locus of decision-making from a single cell to a collective, and how a new space of behavioral complexity might have become accessible in the process.}, } @article {pmid37048099, year = {2023}, author = {Leitner, N and Ertl, R and Gabner, S and Fuchs-Baumgartinger, A and Walter, I and Hlavaty, J}, title = {Isolation and Characterization of Novel Canine Osteosarcoma Cell Lines from Chemotherapy-Naïve Patients.}, journal = {Cells}, volume = {12}, number = {7}, pages = {}, pmid = {37048099}, issn = {2073-4409}, mesh = {Animals ; Dogs ; Cell Line, Tumor ; *Osteosarcoma/pathology ; *MicroRNAs/genetics ; Gene Expression Profiling ; *Bone Neoplasms/metabolism ; }, abstract = {The present study aimed to establish novel canine osteosarcoma cell lines (COS3600, COS3600B, COS4074) and characterize the recently described COS4288 cells. The established D-17 cell line served as a reference. Analyzed cell lines differed notably in their biological characteristics. Calculated doubling times were between 22 h for COS3600B and 426 h for COS4074 cells. COS3600B and COS4288 cells produced visible colonies after anchorage-independent growth in soft agar. COS4288 cells were identified as cells with the highest migratory capacity. All cells displayed the ability to invade through an artificial basement membrane matrix. Immunohistochemical analyses revealed the mesenchymal origin of all COS cell lines as well as positive staining for the osteosarcoma-relevant proteins alkaline phosphatase and karyopherin α2. Expression of p53 was confirmed in all tested cell lines. Gene expression analyses of selected genes linked to cellular immune checkpoints (CD270, CD274, CD276), kinase activity (MET, ERBB2), and metastatic potential (MMP-2, MMP-9) as well as selected long non-coding RNA (MALAT1) and microRNAs (miR-9, miR-34a, miR-93) are provided. All tested cell lines were able to grow as multicellular spheroids. In all spheroids except COS4288, calcium deposition was detected by von Kossa staining. We believe that these new cell lines serve as useful biological models for future studies.}, } @article {pmid37047167, year = {2023}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047167}, issn = {1422-0067}, support = {No. 075-15-2021-1075//Ministry of Science and Higher Education of the Russian Federation/ ; }, mesh = {Animals ; Humans ; Biological Evolution ; *Brachyura ; Carcinogenesis/genetics ; Cell Transformation, Neoplastic ; *Neoplasms/genetics ; }, abstract = {Using meta-analyses, we introduce a unicellular attractor (UCA) model integrating essential features of the 'atavistic reversal', 'cancer attractor', 'somatic mutation', 'genome chaos', and 'tissue organization field' theories. The 'atavistic reversal' theory is taken as a keystone. We propose a possible mechanism of this reversal, its refinement called 'gradual atavism', and evidence for the 'serial atavism' model. We showed the gradual core-to-periphery evolutionary growth of the human interactome resulting in the higher protein interaction density and global interactome centrality in the UC center. In addition, we revealed that UC genes are more actively expressed even in normal cells. The modeling of random walk along protein interaction trajectories demonstrated that random alterations in cellular networks, caused by genetic and epigenetic changes, can result in a further gradual activation of the UC center. These changes can be induced and accelerated by cellular stress that additionally activates UC genes (especially during cell proliferation), because the genes involved in cellular stress response and cell cycle are mostly of UC origin. The functional enrichment analysis showed that cancer cells demonstrate the hyperactivation of energetics and the suppression of multicellular genes involved in communication with the extracellular environment (especially immune surveillance). Collectively, these events can unleash selfish cell behavior aimed at survival at all means. All these changes are boosted by polyploidization. The UCA model may facilitate an understanding of oncogenesis and promote the development of therapeutic strategies.}, } @article {pmid37046079, year = {2023}, author = {Li, G and Chen, L and Pang, K and Tang, Q and Wu, C and Yuan, X and Zhou, C and Xiao, S}, title = {Tonian carbonaceous compressions indicate that Horodyskia is one of the oldest multicellular and coenocytic macro-organisms.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {399}, pmid = {37046079}, issn = {2399-3642}, mesh = {*Eukaryota ; *Fossils ; China ; }, abstract = {Macrofossils with unambiguous biogenic origin and predating the one-billion-year-old multicellular fossils Bangiomorpha and Proterocladus interpreted as crown-group eukaryotes are quite rare. Horodyskia is one of these few macrofossils, and it extends from the early Mesoproterozoic Era to the terminal Ediacaran Period. The biological interpretation of this enigmatic fossil, however, has been a matter of controversy since its discovery in 1982, largely because there was no evidence for the preservation of organic walls. Here we report new carbonaceous compressions of Horodyskia from the Tonian successions (~950-720 Ma) in North China. The macrofossils herein with bona fide organic walls reinforce the biogenicity of Horodyskia. Aided by the new material, we reconstruct Horodyskia as a colonial organism composed of a chain of organic-walled vesicles that likely represent multinucleated (coenocytic) cells of early eukaryotes. Two species of Horodyskia are differentiated on the basis of vesicle sizes, and their co-existence in the Tonian assemblage provides a link between the Mesoproterozoic (H. moniliformis) and the Ediacaran (H. minor) species. Our study thus provides evidence that eukaryotes have acquired macroscopic size through the combination of coenocytism and colonial multicellularity at least ~1.48 Ga, and highlights an exceptionally long range and morphological stasis of this Proterozoic macrofossils.}, } @article {pmid37029839, year = {2023}, author = {Varilla González, JD and Macedo Alves, F and Bagnatori Sartori, ÂL and de Oliveira Arruda, RDC}, title = {Diversity and evolution of leaflet anatomical characters in the Pterocarpus clade (Fabaceae: Papilionoideae).}, journal = {Journal of plant research}, volume = {136}, number = {4}, pages = {453-481}, pmid = {37029839}, issn = {1618-0860}, support = {88882.461305/2019-01//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {Phylogeny ; *Pterocarpus ; *Fabaceae ; Trichomes ; Microscopy, Electron, Scanning ; }, abstract = {The Pterocarpus clade includes 23 genera previously attributed to different Fabaceae tribes. The recent rearrangements of many genera in the clade do not recognize morphological synapomorphies. This study aimed to identify new synapomorphies for the Pterocarpus clade, to identify characters supporting inter-generic relationships currently resolved only by molecular data and to identify diagnostic characters at the genus and species levels. Subterminal leaflets of the studied genera were selected and analyzed using light and scanning electron microscopy. Ancestral reconstruction was performed using morphological and anatomical characters of 16 genera of the Pterocarpus clade. The convex epidermal relief in the region of the main vein indicated the relationship among all genera of the group. Anchor-like multicellular trichomes are features shared by Brya and Cranocarpus, which are the sister group to the other genera of the clade. Subepidermal layers are features shared by the Centrolobium, Etaballia, Paramachaerium, Pterocarpus and Tipuana genera, and the sclerenchyma sheath in the leaflet margin is reported in the Discolobium, Riedeliella and Platymiscium genera. Bulbous based glandular trichomes and vesicular glandular trichomes are diagnostic at the species level in Centrolobium and Pterocarpus, respectively. The leaflet characters investigated can be useful for the taxonomic delimitation at both the genus and species levels of the Pterocarpus clade. Our dataset provides new synapomorphies, elucidates the inter-generic relationships and reinforces the phylogenetic classification of the Pterocarpus clade resolved by molecular data.}, } @article {pmid37023182, year = {2023}, author = {Darras, H and Berney, C and Hasin, S and Drescher, J and Feldhaar, H and Keller, L}, title = {Obligate chimerism in male yellow crazy ants.}, journal = {Science (New York, N.Y.)}, volume = {380}, number = {6640}, pages = {55-58}, doi = {10.1126/science.adf0419}, pmid = {37023182}, issn = {1095-9203}, mesh = {Animals ; Male ; *Ants/cytology/genetics/growth & development ; *Chimerism ; Diploidy ; *Reproduction ; Semen/cytology ; Germ Cells/cytology ; }, abstract = {Multicellular organisms typically develop from a single fertilized egg and therefore consist of clonal cells. We report an extraordinary reproductive system in the yellow crazy ant. Males are chimeras of haploid cells from two divergent lineages: R and W. R cells are overrepresented in the males' somatic tissues, whereas W cells are overrepresented in their sperm. Chimerism occurs when parental nuclei bypass syngamy and divide separately within the same egg. When syngamy takes place, the diploid offspring either develops into a queen when the oocyte is fertilized by an R sperm or into a worker when fertilized by a W sperm. This study reveals a mode of reproduction that may be associated with a conflict between lineages to preferentially enter the germ line.}, } @article {pmid37019107, year = {2023}, author = {Barrere, J and Nanda, P and Murray, AW}, title = {Alternating selection for dispersal and multicellularity favors regulated life cycles.}, journal = {Current biology : CB}, volume = {33}, number = {9}, pages = {1809-1817.e3}, pmid = {37019107}, issn = {1879-0445}, support = {R01 GM043987/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Saccharomyces cerevisiae/physiology ; *Biological Evolution ; Phenotype ; Life Cycle Stages ; Reproduction ; }, abstract = {The evolution of complex multicellularity opened paths to increased morphological diversity and organizational novelty. This transition involved three processes: cells remained attached to one another to form groups, cells within these groups differentiated to perform different tasks, and the groups evolved new reproductive strategies.[1][,][2][,][3][,][4][,][5] Recent experiments identified selective pressures and mutations that can drive the emergence of simple multicellularity and cell differentiation,[6][,][7][,][8][,][9][,][10][,][11] but the evolution of life cycles, particularly how simple multicellular forms reproduce, has been understudied. The selective pressure and mechanisms that produced a regular alternation between single cells and multicellular collectives are still unclear.[12] To probe the factors regulating simple multicellular life cycles, we examined a collection of wild isolates of the budding yeast S. cerevisiae.[12][,][13] We found that all these strains can exist as multicellular clusters, a phenotype that is controlled by the mating-type locus and strongly influenced by the nutritional environment. Inspired by this variation, we engineered inducible dispersal in a multicellular laboratory strain and demonstrated that a regulated life cycle has an advantage over constitutively single-celled or constitutively multicellular life cycles when the environment alternates between favoring intercellular cooperation (a low sucrose concentration) and dispersal (a patchy environment generated by emulsion). Our results suggest that the separation of mother and daughter cells is under selection in wild isolates and is regulated by their genetic composition and the environments they encounter and that alternating patterns of resource availability may have played a role in the evolution of life cycles.}, } @article {pmid37011504, year = {2023}, author = {Morehouse, BR}, title = {Phage defense origin of animal immunity.}, journal = {Current opinion in microbiology}, volume = {73}, number = {}, pages = {102295}, doi = {10.1016/j.mib.2023.102295}, pmid = {37011504}, issn = {1879-0364}, mesh = {Animals ; *Bacteria/genetics ; Prokaryotic Cells ; Archaea/genetics ; Immunity, Innate ; *Bacteriophages/genetics ; }, abstract = {The innate immune system is the first line of defense against microbial pathogens. Many of the features of eukaryotic innate immunity have long been viewed as lineage-specific innovations, evolved to deal with the challenges and peculiarities of multicellular life. However, it has become increasingly apparent that in addition to evolving their own unique antiviral immune strategies, all lifeforms have some shared defense strategies in common. Indeed, critical fixtures of animal innate immunity bear striking resemblance in both structure and function to the multitude of diverse bacteriophage (phage) defense pathways discovered hidden in plain sight within the genomes of bacteria and archaea. This review will highlight many surprising examples of the recently revealed connections between prokaryotic and eukaryotic antiviral immune systems.}, } @article {pmid37005641, year = {2023}, author = {Guan, X and Zhang, L and Lai, S and Zhang, J and Wei, J and Wang, K and Zhang, W and Li, C and Tong, J and Lei, Z}, title = {Green synthesis of glyco-CuInS2 QDs with visible/NIR dual emission for 3D multicellular tumor spheroid and in vivo imaging.}, journal = {Journal of nanobiotechnology}, volume = {21}, number = {1}, pages = {118}, pmid = {37005641}, issn = {1477-3155}, support = {21965032; 22267012; 21761032; 52162034//National Natural Science Foundation of China/ ; 20JR5RA525; 20JR10RA143//Natural Science Foundation of Gansu Province/ ; 2020BSZX08//Doctoral Program Fund of Lanzhou University of Arts and Sciences/ ; }, mesh = {Humans ; Diagnostic Imaging ; *Nanoparticles ; *Quantum Dots ; HeLa Cells ; Water ; }, abstract = {Glyco-quantum dots (glyco-QDs) have attracted significant interest in bioimaging applications, notably in cancer imaging, because they effectively combine the glycocluster effect with the exceptional optical properties of QDs. The key challenge now lies in how to eliminate the high heavy metal toxicity originating from traditional toxic Cd-based QDs for in vivo bioimaging. Herein, we report an eco-friendly pathway to prepare nontoxic Cd-free glyco-QDs in water by the "direct" reaction of thiol-ending monosaccharides with metal salts precursors. The formation of glyco-CuInS2 QDs could be explained by a nucleation-growth mechanism following the LaMer model. As-prepared four glyco-CuInS2 QDs were water-soluble, monodispersed, spherical in shape and exhibited size range of 3.0-4.0 nm. They exhibited well-separated dual emission in the visible region (500-590 nm) and near-infrared range (~ 827 nm), which may be attributable to visible excitonic emission and near-infrared surface defect emission. Meanwhile, the cell imaging displayed the reversibly distinct dual-color (green and red) fluorescence in tumor cells (HeLa, A549, MKN-45) and excellent membrane-targeting properties of glyco-CuInS2 QDs based on their good biorecognition ability. Importantly, these QDs succeed in penetrating uniformly into the interior (the necrotic zone) of 3D multicellular tumor spheroids (MCTS) due to their high negative charge (zeta potential values ranging from - 23.9 to - 30.1 mV), which overcame the problem of poor penetration depth of existing QDs in in vitro spheroid models. So, confocal analysis confirmed their excellent ability to penetrate and label tumors. Thus, the successful application in in vivo bioimaging of these glyco-QDs verified that this design strategy is an effective, low cost and simple procedure for developing green nanoparticles as cheap and promising fluorescent bioprobes.}, } @article {pmid37005419, year = {2023}, author = {Tang, SK and Zhi, XY and Zhang, Y and Makarova, KS and Liu, BB and Zheng, GS and Zhang, ZP and Zheng, HJ and Wolf, YI and Zhao, YR and Jiang, SH and Chen, XM and Li, EY and Zhang, T and Chen, PR and Feng, YZ and Xiang, MX and Lin, ZQ and Shi, JH and Chang, C and Zhang, X and Li, R and Lou, K and Wang, Y and Chang, L and Yin, M and Yang, LL and Gao, HY and Zhang, ZK and Tao, TS and Guan, TW and He, FC and Lu, YH and Cui, HL and Koonin, EV and Zhao, GP and Xu, P}, title = {Cellular differentiation into hyphae and spores in halophilic archaea.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {1827}, pmid = {37005419}, issn = {2041-1723}, mesh = {Hyphae/genetics ; Proteomics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Streptomyces/genetics ; *Halobacteriaceae/genetics ; Spores ; Cell Differentiation ; Sequence Analysis, DNA ; China ; }, abstract = {Several groups of bacteria have complex life cycles involving cellular differentiation and multicellular structures. For example, actinobacteria of the genus Streptomyces form multicellular vegetative hyphae, aerial hyphae, and spores. However, similar life cycles have not yet been described for archaea. Here, we show that several haloarchaea of the family Halobacteriaceae display a life cycle resembling that of Streptomyces bacteria. Strain YIM 93972 (isolated from a salt marsh) undergoes cellular differentiation into mycelia and spores. Other closely related strains are also able to form mycelia, and comparative genomic analyses point to gene signatures (apparent gain or loss of certain genes) that are shared by members of this clade within the Halobacteriaceae. Genomic, transcriptomic and proteomic analyses of non-differentiating mutants suggest that a Cdc48-family ATPase might be involved in cellular differentiation in strain YIM 93972. Additionally, a gene encoding a putative oligopeptide transporter from YIM 93972 can restore the ability to form hyphae in a Streptomyces coelicolor mutant that carries a deletion in a homologous gene cluster (bldKA-bldKE), suggesting functional equivalence. We propose strain YIM 93972 as representative of a new species in a new genus within the family Halobacteriaceae, for which the name Actinoarchaeum halophilum gen. nov., sp. nov. is herewith proposed. Our demonstration of a complex life cycle in a group of haloarchaea adds a new dimension to our understanding of the biological diversity and environmental adaptation of archaea.}, } @article {pmid37002899, year = {2023}, author = {LeBleu, VS and Dai, J and Tsutakawa, S and MacDonald, BA and Alge, JL and Sund, M and Xie, L and Sugimoto, H and Tainer, J and Zon, LI and Kalluri, R}, title = {Identification of unique α4 chain structure and conserved antiangiogenic activity of α3NC1 type IV collagen in zebrafish.}, journal = {Developmental dynamics : an official publication of the American Association of Anatomists}, volume = {252}, number = {7}, pages = {1046-1060}, doi = {10.1002/dvdy.590}, pmid = {37002899}, issn = {1097-0177}, mesh = {Animals ; Humans ; *Collagen Type IV/genetics ; *Zebrafish ; Endothelial Cells ; Protein Subunits/analysis/metabolism ; Basement Membrane/metabolism ; }, abstract = {BACKGROUND: Type IV collagen is an abundant component of basement membranes in all multicellular species and is essential for the extracellular scaffold supporting tissue architecture and function. Lower organisms typically have two type IV collagen genes, encoding α1 and α2 chains, in contrast with the six genes in humans, encoding α1-α6 chains. The α chains assemble into trimeric protomers, the building blocks of the type IV collagen network. The detailed evolutionary conservation of type IV collagen network remains to be studied.

RESULTS: We report on the molecular evolution of type IV collagen genes. The zebrafish α4 non-collagenous (NC1) domain, in contrast with its human ortholog, contains an additional cysteine residue and lacks the M93 and K211 residues involved in sulfilimine bond formation between adjacent protomers. This may alter α4 chain interactions with other α chains, as supported by temporal and anatomic expression patterns of collagen IV chains during the zebrafish development. Despite the divergence between zebrafish and human α3 NC1 domain (endogenous angiogenesis inhibitor, Tumstatin), the zebrafish α3 NC1 domain exhibits conserved antiangiogenic activity in human endothelial cells.

CONCLUSIONS: Our work supports type IV collagen is largely conserved between zebrafish and humans, with a possible difference involving the α4 chain.}, } @article {pmid37002250, year = {2023}, author = {Jiménez-Marín, B and Rakijas, JB and Tyagi, A and Pandey, A and Hanschen, ER and Anderson, J and Heffel, MG and Platt, TG and Olson, BJSC}, title = {Gene loss during a transition to multicellularity.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {5268}, pmid = {37002250}, issn = {2045-2322}, mesh = {*Biological Evolution ; Phylogeny ; }, abstract = {Multicellular evolution is a major transition associated with momentous diversification of multiple lineages and increased developmental complexity. The volvocine algae comprise a valuable system for the study of this transition, as they span from unicellular to undifferentiated and differentiated multicellular morphologies despite their genomes being similar, suggesting multicellular evolution requires few genetic changes to undergo dramatic shifts in developmental complexity. Here, the evolutionary dynamics of six volvocine genomes were examined, where a gradual loss of genes was observed in parallel to the co-option of a few key genes. Protein complexes in the six species exhibited novel interactions, suggesting that gene loss could play a role in evolutionary novelty. This finding was supported by gene network modeling, where gene loss outpaces gene gain in generating novel stable network states. These results suggest gene loss, in addition to gene gain and co-option, may be important for the evolution developmental complexity.}, } @article {pmid37000909, year = {2023}, author = {Little, JC and Kaaronen, RO and Hukkinen, JI and Xiao, S and Sharpee, T and Farid, AM and Nilchiani, R and Barton, CM}, title = {Earth Systems to Anthropocene Systems: An Evolutionary, System-of-Systems, Convergence Paradigm for Interdependent Societal Challenges.}, journal = {Environmental science & technology}, volume = {57}, number = {14}, pages = {5504-5520}, doi = {10.1021/acs.est.2c06203}, pmid = {37000909}, issn = {1520-5851}, mesh = {Animals ; Humans ; *Agriculture ; *Biodiversity ; Urbanization ; Mammals ; }, abstract = {Humans have made profound changes to the Earth. The resulting societal challenges of the Anthropocene (e.g., climate change and impacts, renewable energy, adaptive infrastructure, disasters, pandemics, food insecurity, and biodiversity loss) are complex and systemic, with causes, interactions, and consequences that cascade across a globally connected system of systems. In this Critical Review, we turn to our "origin story" for insight, briefly tracing the formation of the Universe and the Earth, the emergence of life, the evolution of multicellular organisms, mammals, primates, and humans, as well as the more recent societal transitions involving agriculture, urbanization, industrialization, and computerization. Focusing on the evolution of the Earth, genetic evolution, the evolution of the brain, and cultural evolution, which includes technological evolution, we identify a nested evolutionary sequence of geophysical, biophysical, sociocultural, and sociotechnical systems, emphasizing the causal mechanisms that first formed, and then transformed, Earth systems into Anthropocene systems. Describing how the Anthropocene systems coevolved, and briefly illustrating how the ensuing societal challenges became tightly integrated across multiple spatial, temporal, and organizational scales, we conclude by proposing an evolutionary, system-of-systems, convergence paradigm for the entire family of interdependent societal challenges of the Anthropocene.}, } @article {pmid36996815, year = {2023}, author = {Olivetta, M and Dudin, O}, title = {The nuclear-to-cytoplasmic ratio drives cellularization in the close animal relative Sphaeroforma arctica.}, journal = {Current biology : CB}, volume = {33}, number = {8}, pages = {1597-1605.e3}, doi = {10.1016/j.cub.2023.03.019}, pmid = {36996815}, issn = {1879-0445}, mesh = {Animals ; *Eukaryota/genetics ; *Mesomycetozoea/genetics ; Cell Nucleus ; Cytosol ; Genome ; }, abstract = {The ratio of nuclear content to cytoplasmic volume (N/C ratio) is a key regulator driving the maternal-to-zygotic transition in most animal embryos. Altering this ratio often impacts zygotic genome activation and deregulates the timing and outcome of embryogenesis.[1][,][2][,][3] Despite being ubiquitous across animals, little is known about when the N/C ratio evolved to control multicellular development. Such capacity either originated with the emergence of animal multicellularity or was co-opted from the mechanisms present in unicellular organisms.[4] An effective strategy to tackle this question is to investigate the close relatives of animals exhibiting life cycles with transient multicellular stages.[5] Among these are ichthyosporeans, a lineage of protists undergoing coenocytic development followed by cellularization and cell release.[6][,][7][,][8] During cellularization, a transient multicellular stage resembling animal epithelia is generated, offering a unique opportunity to examine whether the N/C ratio regulates multicellular development. Here, we use time-lapse microscopy to characterize how the N/C ratio affects the life cycle of the best-studied ichthyosporean model, Sphaeroforma arctica. We uncover that the last stages of cellularization coincide with a significant increase in the N/C ratio. Increasing the N/C ratio by reducing the coenocytic volume accelerates cellularization, whereas decreasing the N/C ratio by lowering the nuclear content halts it. Moreover, centrifugation and pharmacological inhibitor experiments suggest that the N/C ratio is locally sensed at the cortex and relies on phosphatase activity. Altogether, our results show that the N/C ratio drives cellularization in S. arctica, suggesting that its capacity to control multicellular development predates animal emergence.}, } @article {pmid36996248, year = {2023}, author = {Herold, J and Behle, E and Rosenbauer, J and Ferruzzi, J and Schug, A}, title = {Development of a scoring function for comparing simulated and experimental tumor spheroids.}, journal = {PLoS computational biology}, volume = {19}, number = {3}, pages = {e1010471}, pmid = {36996248}, issn = {1553-7358}, support = {U01 CA202123/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Spheroids, Cellular ; Collagen/chemistry ; Extracellular Matrix ; *Neoplasms ; *Neoplasms, Experimental ; }, abstract = {Progress continues in the field of cancer biology, yet much remains to be unveiled regarding the mechanisms of cancer invasion. In particular, complex biophysical mechanisms enable a tumor to remodel the surrounding extracellular matrix (ECM), allowing cells to invade alone or collectively. Tumor spheroids cultured in collagen represent a simplified, reproducible 3D model system, which is sufficiently complex to recapitulate the evolving organization of cells and interaction with the ECM that occur during invasion. Recent experimental approaches enable high resolution imaging and quantification of the internal structure of invading tumor spheroids. Concurrently, computational modeling enables simulations of complex multicellular aggregates based on first principles. The comparison between real and simulated spheroids represents a way to fully exploit both data sources, but remains a challenge. We hypothesize that comparing any two spheroids requires first the extraction of basic features from the raw data, and second the definition of key metrics to match such features. Here, we present a novel method to compare spatial features of spheroids in 3D. To do so, we define and extract features from spheroid point cloud data, which we simulated using Cells in Silico (CiS), a high-performance framework for large-scale tissue modeling previously developed by us. We then define metrics to compare features between individual spheroids, and combine all metrics into an overall deviation score. Finally, we use our features to compare experimental data on invading spheroids in increasing collagen densities. We propose that our approach represents the basis for defining improved metrics to compare large 3D data sets. Moving forward, this approach will enable the detailed analysis of spheroids of any origin, one application of which is informing in silico spheroids based on their in vitro counterparts. This will enable both basic and applied researchers to close the loop between modeling and experiments in cancer research.}, } @article {pmid36992628, year = {2023}, author = {Östmans, R and Cortes Ruiz, MF and Rostami, J and Sellman, FA and Wågberg, L and Lindström, SB and Benselfelt, T}, title = {Elastoplastic behavior of anisotropic, physically crosslinked hydrogel networks comprising stiff, charged fibrils in an electrolyte.}, journal = {Soft matter}, volume = {19}, number = {15}, pages = {2792-2800}, doi = {10.1039/d2sm01571d}, pmid = {36992628}, issn = {1744-6848}, abstract = {Fibrillar hydrogels are remarkably stiff, low-density networks that can hold vast amounts of water. These hydrogels can easily be made anisotropic by orienting the fibrils using different methods. Unlike the detailed and established descriptions of polymer gels, there is no coherent theoretical framework describing the elastoplastic behavior of fibrillar gels, especially concerning anisotropy. In this work, the swelling pressures of anisotropic fibrillar hydrogels made from cellulose nanofibrils were measured in the direction perpendicular to the fibril alignment. This experimental data was used to develop a model comprising three mechanical elements representing the network and the osmotic pressure due to non-ionic and ionic surface groups on the fibrils. At low solidity, the stiffness of the hydrogels was dominated by the ionic swelling pressure governed by the osmotic ingress of water. Fibrils with different functionality show the influence of aspect ratio, chemical functionality, and the remaining amount of hemicelluloses. This general model describes physically crosslinked hydrogels comprising fibrils with high flexural rigidity - that is, with a persistence length larger than the mesh size. The experimental technique is a framework to study and understand the importance of fibrillar networks for the evolution of multicellular organisms, like plants, and the influence of different components in plant cell walls.}, } @article {pmid36985211, year = {2023}, author = {Li, AQ and Zhang, WJ and Li, XG and Bao, XC and Qi, XQ and Wu, LF and Bartlett, DH}, title = {Piezophilic Phenotype Is Growth Condition Dependent and Correlated with the Regulation of Two Sets of ATPase in Deep-Sea Piezophilic Bacterium Photobacterium profundum SS9.}, journal = {Microorganisms}, volume = {11}, number = {3}, pages = {}, pmid = {36985211}, issn = {2076-2607}, support = {ZDKJ2021028 and ZDKJ2019011//Key Research and Development Program of Hainan Province/ ; NSFC42076127, 42176121 and 91751108//National Natural Science Foundation of China/ ; 2018YD01//Sanya city/ ; }, abstract = {Alteration of respiratory components as a function of pressure is a common strategy developed in deep-sea microorganisms, presumably to adapt to high hydrostatic pressure (HHP). While the electron transport chain and terminal reductases have been extensively studied in deep-sea bacteria, little is known about their adaptations for ATP generation. In this study, we showed that the deep-sea bacterium Photobacterium profundum SS9 exhibits a more pronounced piezophilic phenotype when grown in minimal medium supplemented with glucose (MG) than in the routinely used MB2216 complex medium. The intracellular ATP level varied with pressure, but with opposite trends in the two culture media. Between the two ATPase systems encoded in SS9, ATPase-I played a dominant role when cultivated in MB2216, whereas ATPase-II was more abundant in the MG medium, especially at elevated pressure when cells had the lowest ATP level among all conditions tested. Further analyses of the ΔatpI, ΔatpE1 and ΔatpE2 mutants showed that disrupting ATPase-I induced expression of ATPase-II and that the two systems are functionally redundant in MB2216. Collectively, we provide the first examination of the differences and relationships between two ATPase systems in a piezophilic bacterium, and expanded our understanding of the involvement of energy metabolism in pressure adaptation.}, } @article {pmid36980921, year = {2023}, author = {Han, M and Ren, J and Guo, H and Tong, X and Hu, H and Lu, K and Dai, Z and Dai, F}, title = {Mutation Rate and Spectrum of the Silkworm in Normal and Temperature Stress Conditions.}, journal = {Genes}, volume = {14}, number = {3}, pages = {}, pmid = {36980921}, issn = {2073-4425}, mesh = {Animals ; *Bombyx/genetics ; Temperature ; Mutation Rate ; Insecta/genetics ; Genome ; }, abstract = {Mutation rate is a crucial parameter in evolutionary genetics. However, the mutation rate of most species as well as the extent to which the environment can alter the genome of multicellular organisms remain poorly understood. Here, we used parents-progeny sequencing to investigate the mutation rate and spectrum of the domestic silkworm (Bombyx mori) among normal and two temperature stress conditions (32 °C and 0 °C). The rate of single-nucleotide mutations in the normal temperature rearing condition was 0.41 × 10[-8] (95% confidence interval, 0.33 × 10[-8]-0.49 × 10[-8]) per site per generation, which was up to 1.5-fold higher than in four previously studied insects. Moreover, the mutation rates of the silkworm under the stresses are significantly higher than in normal conditions. Furthermore, the mutation rate varies less in gene regions under normal and temperature stresses. Together, these findings expand the known diversity of the mutation rate among eukaryotes but also have implications for evolutionary analysis that assumes a constant mutation rate among species and environments.}, } @article {pmid36980213, year = {2023}, author = {Merino, MM and Garcia-Sanz, JA}, title = {Stemming Tumoral Growth: A Matter of Grotesque Organogenesis.}, journal = {Cells}, volume = {12}, number = {6}, pages = {}, pmid = {36980213}, issn = {2073-4409}, mesh = {Humans ; *Neoplasm Recurrence, Local ; *Organogenesis ; Neoplastic Stem Cells ; Cell Transformation, Neoplastic ; }, abstract = {The earliest metazoans probably evolved from single-celled organisms which found the colonial system to be a beneficial organization. Over the course of their evolution, these primary colonial organisms increased in size, and division of labour among the cells became a remarkable feature, leading to a higher level of organization: the biological organs. Primitive metazoans were the first organisms in evolution to show organ-type structures, which set the grounds for complex organs to evolve. Throughout evolution, and concomitant with organogenesis, is the appearance of tissue-specific stem cells. Tissue-specific stem cells gave rise to multicellular living systems with distinct organs which perform specific physiological functions. This setting is a constructive role of evolution; however, rebel cells can take over the molecular mechanisms for other purposes: nowadays we know that cancer stem cells, which generate aberrant organ-like structures, are at the top of a hierarchy. Furthermore, cancer stem cells are the root of metastasis, therapy resistance, and relapse. At present, most therapeutic drugs are unable to target cancer stem cells and therefore, treatment becomes a challenging issue. We expect that future research will uncover the mechanistic "forces" driving organ growth, paving the way to the implementation of new strategies to impair human tumorigenesis.}, } @article {pmid36964572, year = {2023}, author = {Barrera-Redondo, J and Lotharukpong, JS and Drost, HG and Coelho, SM}, title = {Uncovering gene-family founder events during major evolutionary transitions in animals, plants and fungi using GenEra.}, journal = {Genome biology}, volume = {24}, number = {1}, pages = {54}, pmid = {36964572}, issn = {1474-760X}, mesh = {Animals ; Phylogeny ; *Biological Evolution ; *Genomics/methods ; Fungi/genetics ; Plants/genetics ; Evolution, Molecular ; }, abstract = {We present GenEra (https://github.com/josuebarrera/GenEra), a DIAMOND-fueled gene-family founder inference framework that addresses previously raised limitations and biases in genomic phylostratigraphy, such as homology detection failure. GenEra also reduces computational time from several months to a few days for any genome of interest. We analyze the emergence of taxonomically restricted gene families during major evolutionary transitions in plants, animals, and fungi. Our results indicate that the impact of homology detection failure on inferred patterns of gene emergence is lineage-dependent, suggesting that plants are more prone to evolve novelty through the emergence of new genes compared to animals and fungi.}, } @article {pmid36959212, year = {2023}, author = {Nofech-Mozes, I and Soave, D and Awadalla, P and Abelson, S}, title = {Pan-cancer classification of single cells in the tumour microenvironment.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {1615}, pmid = {36959212}, issn = {2041-1723}, mesh = {Humans ; Female ; *Tumor Microenvironment ; *Breast Neoplasms/pathology ; Gene Expression Profiling/methods ; Transcriptome ; Stromal Cells/pathology ; }, abstract = {Single-cell RNA sequencing can reveal valuable insights into cellular heterogeneity within tumour microenvironments (TMEs), paving the way for a deep understanding of cellular mechanisms contributing to cancer. However, high heterogeneity among the same cancer types and low transcriptomic variation in immune cell subsets present challenges for accurate, high-resolution confirmation of cells' identities. Here we present scATOMIC; a modular annotation tool for malignant and non-malignant cells. We trained scATOMIC on >300,000 cancer, immune, and stromal cells defining a pan-cancer reference across 19 common cancers and employ a hierarchical approach, outperforming current classification methods. We extensively confirm scATOMIC's accuracy on 225 tumour biopsies encompassing >350,000 cancer and a variety of TME cells. Lastly, we demonstrate scATOMIC's practical significance to accurately subset breast cancers into clinically relevant subtypes and predict tumours' primary origin across metastatic cancers. Our approach represents a broadly applicable strategy to analyse multicellular cancer TMEs.}, } @article {pmid36951905, year = {2023}, author = {Jiao, ZX and Li, XG and Zhang, HH and Xu, J and Bai, SJ and Dai, J and Lin, J and Zhang, WJ and Qi, XQ and Wu, LF}, title = {Crassaminicella indica sp. nov., a novel thermophilic anaerobic bacterium isolated from a deep-sea hydrothermal vent.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {73}, number = {3}, pages = {}, doi = {10.1099/ijsem.0.005725}, pmid = {36951905}, issn = {1466-5034}, mesh = {*Fatty Acids/chemistry ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Base Composition ; *Hydrothermal Vents/microbiology ; Anaerobiosis ; Sequence Analysis, DNA ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Phospholipids/chemistry ; Bacteria, Anaerobic ; }, abstract = {A novel moderately thermophilic heterotrophic bacterium, designated strain 143-21[T], was isolated from a deep-sea hydrothermal chimney sample collected from the Central Indian Ridge at a depth of 2 440 m. Phylogenetic analysis indicated that strain 143-21[T] belongs to the genus Crassaminicella. It was most closely related to Crassaminicella thermophila SY095[T] (96.79 % 16S rRNA gene sequence similarity) and Crassaminicella profunda Ra1766H[T] (96.52 %). Genomic analysis showed that strain 143-21[T] shares 79.79-84.45 % average nucleotide identity and 23.50-29.20 % digital DNA-DNA hybridization with the species of the genus Crassaminicella, respectively. Cells were rod-shaped, non-motile, Gram-positive-staining. Terminal endospores were observed in stationary-phase cells when strain 143-21[T] was grown on Thermococcales rich medium. Strain 143-21[T] was able to grow at 30-60 °C (optimum, 50 °C), pH 6.5-8.5 (optimum, pH 7.0) and in 1.0-7.0 % NaCl (w/v; optimum 2.0 %, w/v). Strain 143-21[T] utilized fructose, glucose, maltose, mannose, ribose, N-acetyl-d-(+)-glucosamine and casamino acids, as well as amino acids including glutamate, lysine, histidine and cysteine. The main fermentation products from glucose were acetate (2.07 mM), H2 and CO2. It did not reduce elemental sulphur, sulphate, thiosulphate, sulphite, fumarate, nitrate, nitrite and Fe (III). The predominant cellular fatty acids were C14 : 0 (48.8 %), C16 : 0 (12.9 %), and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 10.2 %). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol, as well as two unidentified phospholipids and four unidentified aminolipids. No respiratory quinones were detected. Based on its phylogenetic analysis and physiological characteristics, strain 143-21[T] is considered to represent a novel species of the genus Crassaminicella, for which the name Crassaminicella indica sp. nov. is proposed. The type strain is strain 143-21[T] (=DSM 114408[T]= MCCC 1K06400[T]).}, } @article {pmid36945744, year = {2023}, author = {Li, Y and Kim, EJ and Voshall, A and Moriyama, EN and Cerutti, H}, title = {Small RNAs >26 nt in length associate with AGO1 and are upregulated by nutrient deprivation in the alga Chlamydomonas.}, journal = {The Plant cell}, volume = {35}, number = {6}, pages = {1868-1887}, pmid = {36945744}, issn = {1532-298X}, mesh = {Animals ; *Chlamydomonas/genetics/metabolism ; RNA Interference ; Gene Expression Regulation ; Argonaute Proteins/genetics/metabolism ; *Chlamydomonas reinhardtii/genetics/metabolism ; }, abstract = {Small RNAs (sRNAs) associate with ARGONAUTE (AGO) proteins forming effector complexes with key roles in gene regulation and defense responses against molecular parasites. In multicellular eukaryotes, extensive duplication and diversification of RNA interference (RNAi) components have resulted in intricate pathways for epigenetic control of gene expression. The unicellular alga Chlamydomonas reinhardtii also has a complex RNAi machinery, including 3 AGOs and 3 DICER-like proteins. However, little is known about the biogenesis and function of most endogenous sRNAs. We demonstrate here that Chlamydomonas contains uncommonly long (>26 nt) sRNAs that associate preferentially with AGO1. Somewhat reminiscent of animal PIWI-interacting RNAs, these >26 nt sRNAs are derived from moderately repetitive genomic clusters and their biogenesis is DICER-independent. Interestingly, the sequences generating these >26-nt sRNAs have been conserved and amplified in several Chlamydomonas species. Moreover, expression of these longer sRNAs increases substantially under nitrogen or sulfur deprivation, concurrently with the downregulation of predicted target transcripts. We hypothesize that the transposon-like sequences from which >26-nt sRNAs are produced might have been ancestrally targeted for silencing by the RNAi machinery but, during evolution, certain sRNAs might have fortuitously acquired endogenous target genes and become integrated into gene regulatory networks.}, } @article {pmid36915469, year = {2023}, author = {Prieto, I and Barbáchano, A and Rodríguez-Salas, N and Viñal, D and Cortés-Guiral, D and Muñoz, A and Fernández-Barral, A}, title = {Tailored chemotherapy for colorectal cancer peritoneal metastases based on a drug-screening platform in patient-derived organoids: a case report.}, journal = {Journal of gastrointestinal oncology}, volume = {14}, number = {1}, pages = {442-449}, pmid = {36915469}, issn = {2078-6891}, abstract = {BACKGROUND: Peritoneal metastasis from colorectal cancer (CRC) has limited therapeutic options and poor prognosis. Systemic chemotherapy combined with cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) or pressurized intraperitoneal aerosol chemotherapy (PIPAC) have yielded initial promising results. However, standard local therapies with oxaliplatin and mitomycin are not optimal and a better individualized management of these patients remains as an unmet clinical need. Patient-derived organoid (PDO) technology allows to culture in three dimensions normal and cancer stem cells (CSC) that self-organize in multicellular structures that recapitulates some of the features of the particular organ or tumor of origin, emerging as a promising tool for drug-testing and precision medicine. This technology could improve the efficacy of systemic and intraperitoneal chemotherapy and avoid unnecessary treatments and side effects to the patient.

CASE DESCRIPTION: Here we report a case of a 45-year-old man with a rectal adenocarcinoma with liver, lymph node and peritoneal metastases. The patient was treated with systemic chemotherapy (FOLFOXIRI plus Bevacizumab) and was subjected to mitomycin-based PIPAC. We generated patient-derived peritoneal carcinomatosis organoids in order to screen the activity of drugs for a personalized treatment. Both 5-FU and SN-38, the active irinotecan derivative, displayed strong cytotoxicity, while the response to oxaliplatin was much lower. Although the development of a colo-cutaneous fistulae prevented from further PIPAC, the patient continued with fluoropirimidine maintenance treatment based on standard clinical practice and the drug-screening test performed on organoids.

CONCLUSIONS: Our results suggest that the peritoneal implant shows chemoresistance to oxaliplatin, while it might still be sensitive to irinotecan and 5-FU, which supports a potential benefit of these two drugs in the local and/or systemic treatment of our patient. This study shows the strength of the utility of the establishment of organoids for drug response assays and thus, for the personalized treatment of colorectal carcinomatosis patients.}, } @article {pmid36912901, year = {2023}, author = {Ebinghaus, M and Dos Santos, MDM and Tonelli, GSSS and Macagnan, D and Carvalho, EA and Dianese, JC}, title = {Raveneliopsis, a new genus of ravenelioid rust fungi on Cenostigma (Caesalpinioideae) from the Brazilian Cerrado and Caatinga.}, journal = {Mycologia}, volume = {115}, number = {2}, pages = {263-276}, doi = {10.1080/00275514.2023.2177048}, pmid = {36912901}, issn = {1557-2536}, mesh = {Brazil ; Phylogeny ; *Basidiomycota/genetics ; *Fabaceae ; }, abstract = {The multicellular discoid convex teliospore heads represent a prominent generic feature of the genus Ravenelia. However, recent molecular phylogenetic work has shown that this is a convergent trait, and that this genus does not represent a natural group. In 2000, a rust fungus infecting the Caesalpinioid species Cenostigma macrophyllum (= C. gardnerianum) was described as Ravenelia cenostigmatis. This species shows some rare features, such as an extra layer of sterile cells between the cysts and the fertile teliospores, spirally ornamented urediniospores, as well as strongly incurved paraphyses giving the telia and uredinia a basket-like appearance. Using freshly collected specimens of Rav. cenostigmatis and Rav. spiralis on C. macrophyllum, our phylogenetic analyses based on the nuc 28S, nuc 18S, and mt CO3 (cytochrome c oxidase subunit 3) gene sequences demonstrated that these two rust fungi belong in a lineage within the Raveneliineae that is distinct from Ravenelia s. str. Besides proposing their recombination into the new genus Raveneliopsis (type species R. cenostigmatis) and briefly discussing their potentially close phylogenetic affiliations, we suggest that five other Ravenelia species that are morphologically and ecologically close to the type species of Raveneliopsis, i.e., Rav. corbula, Rav. corbuloides, Rav. parahybana, Rav. pileolarioides, and Rav. Striatiformis, may be recombined pending new collections and confirmation through molecular phylogenetic analyses.}, } @article {pmid36909237, year = {2023}, author = {Bajgar, A and Krejčová, G}, title = {On the origin of the functional versatility of macrophages.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1128984}, pmid = {36909237}, issn = {1664-042X}, abstract = {Macrophages represent the most functionally versatile cells in the animal body. In addition to recognizing and destroying pathogens, macrophages remove senescent and exhausted cells, promote wound healing, and govern tissue and metabolic homeostasis. In addition, many specialized populations of tissue-resident macrophages exhibit highly specialized functions essential for the function of specific organs. Sometimes, however, macrophages cease to perform their protective function and their seemingly incomprehensible response to certain stimuli leads to pathology. In this study, we address the question of the origin of the functional versatility of macrophages. To this end, we have searched for the evolutionary origin of macrophages themselves and for the emergence of their characteristic properties. We hypothesize that many of the characteristic features of proinflammatory macrophages evolved in the unicellular ancestors of animals, and that the functional repertoire of macrophage-like amoebocytes further expanded with the evolution of multicellularity and the increasing complexity of tissues and organ systems. We suggest that the entire repertoire of macrophage functions evolved by repurposing and diversification of basic functions that evolved early in the evolution of metazoans under conditions barely comparable to that in tissues of multicellular organisms. We believe that by applying this perspective, we may find an explanation for the otherwise counterintuitive behavior of macrophages in many human pathologies.}, } @article {pmid36907967, year = {2023}, author = {Lu, B and Hu, X and Warren, A and Song, W and Yan, Y}, title = {From oral structure to molecular evidence: new insights into the evolutionary phylogeny of the ciliate order Sessilida (Protista, Ciliophora), with the establishment of two new families and new contributions to the poorly studied family Vaginicolidae.}, journal = {Science China. Life sciences}, volume = {66}, number = {7}, pages = {1535-1553}, pmid = {36907967}, issn = {1869-1889}, mesh = {Humans ; Phylogeny ; *Ciliophora/genetics ; *Oligohymenophorea/genetics ; DNA, Ribosomal/genetics ; Cognition ; Sequence Analysis, DNA ; }, abstract = {Ciliated protists represent one of the most primitive and diverse lineages of eukaryotes, with nuclear dimorphism, a distinctive sexual process (conjugation), and extensive genome rearrangements. Among divergent ciliate lineages, the peritrich order Sessilida includes members with a colonial lifestyle, which may hint to an independent evolutionary attempt for multicellularity, although they are still single-celled organisms. To date, the evolution and phylogeny of this group are still far from clear, in part due to the paucity of molecular and/or morphological data for many taxa. In this study, we extend taxon sampling of a loricate group of sessilids by obtaining 69 new rDNA (SSU rDNA, ITS1-5.8S rDNA-ITS2, and LSU rDNA) sequences from 20 well-characterized representative species and analyze the phylogenetic relationships within Sessilida. The main findings are: (i) the genera Rhabdostyla and Campanella each represents a unique taxon at family level, supporting the establishment of two new families, i.e., Rhabdostylidae n. fam. and Campanellidae n. fam., respectively, the former being sister to a morphologically heterogeneous clade comprising Astylozoidae and several incertae sedis species and the latter occupying the basal position within the Sessilida clade; (ii) the structure of infundibular polykinety 3 is likely to be a phylogenetically informative character for resolving evolutionary relationships among sessilids; (iii) differences between sparsely and the densely arranged silverline systems could be a suprageneric taxonomic character; (iv) the monophyly of Vaginicolidae is confirmed, which is consistent with its specialized morphology, i.e., the possession of a typical peritrich lorica which might be an apomorphy for this group; (v) within Vaginicolidae, the monotypic Cothurniopsis sensu Stokes, 1893 is a synonym of Cothurnia Ehrenberg, 1831, and a new combination is created, i.e., Cothurnia valvata nov. comb.; (vi) Vaginicola sensu lato comprises at least two distinctly divergent clades, one affiliated with Thuricola and the other with a systematically puzzling clade represented by Vaginicola tincta.}, } @article {pmid36899423, year = {2023}, author = {Ouyang, X and Wu, B and Yu, H and Dong, B}, title = {DYRK1-mediated phosphorylation of endocytic components is required for extracellular lumen expansion in ascidian notochord.}, journal = {Biological research}, volume = {56}, number = {1}, pages = {10}, pmid = {36899423}, issn = {0717-6287}, support = {2019YFE0190900//National Key Research and Development Program of China/ ; }, mesh = {Animals ; Humans ; *Ciona intestinalis/metabolism ; Notochord/metabolism ; Phosphorylation ; Embryonic Development ; Morphogenesis ; }, abstract = {BACKGROUND: The biological tube is a basal biology structure distributed in all multicellular animals, from worms to humans, and has diverse biological functions. Formation of tubular system is crucial for embryogenesis and adult metabolism. Ascidian Ciona notochord lumen is an excellent in vivo model for tubulogenesis. Exocytosis has been known to be essential for tubular lumen formation and expansion. The roles of endocytosis in tubular lumen expansion remain largely unclear.

RESULTS: In this study, we first identified a dual specificity tyrosine-phosphorylation-regulated kinase 1 (DYRK1), the protein kinase, which was upregulated and required for ascidian notochord extracellular lumen expansion. We demonstrated that DYRK1 interacted with and phosphorylated one of the endocytic components endophilin at Ser263 that was essential for notochord lumen expansion. Moreover, through phosphoproteomic sequencing, we revealed that in addition to endophilin, the phosphorylation of other endocytic components was also regulated by DYRK1. The loss of function of DYRK1 disturbed endocytosis. Then, we demonstrated that clathrin-mediated endocytosis existed and was required for notochord lumen expansion. In the meantime, the results showed that the secretion of notochord cells is vigorous in the apical membrane.

CONCLUSIONS: We found the co-existence of endocytosis and exocytosis activities in apical membrane during lumen formation and expansion in Ciona notochord. A novel signaling pathway is revealed that DYRK1 regulates the endocytosis by phosphorylation that is required for lumen expansion. Our finding thus indicates a dynamic balance between endocytosis and exocytosis is crucial to maintain apical membrane homeostasis that is essential for lumen growth and expansion in tubular organogenesis.}, } @article {pmid36897970, year = {2023}, author = {Davidescu, MR and Romanczuk, P and Gregor, T and Couzin, ID}, title = {Growth produces coordination trade-offs in Trichoplax adhaerens, an animal lacking a central nervous system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {11}, pages = {e2206163120}, pmid = {36897970}, issn = {1091-6490}, support = {R01 GM097275/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Placozoa/physiology ; Body Size ; Central Nervous System ; Biological Evolution ; }, abstract = {How collectives remain coordinated as they grow in size is a fundamental challenge affecting systems ranging from biofilms to governments. This challenge is particularly apparent in multicellular organisms, where coordination among a vast number of cells is vital for coherent animal behavior. However, the earliest multicellular organisms were decentralized, with indeterminate sizes and morphologies, as exemplified by Trichoplax adhaerens, arguably the earliest-diverged and simplest motile animal. We investigated coordination among cells in T. adhaerens by observing the degree of collective order in locomotion across animals of differing sizes and found that larger individuals exhibit increasingly disordered locomotion. We reproduced this effect of size on order through a simulation model of active elastic cellular sheets and demonstrate that this relationship is best recapitulated across all body sizes when the simulation parameters are tuned to a critical point in the parameter space. We quantify the trade-off between increasing size and coordination in a multicellular animal with a decentralized anatomy that shows evidence of criticality and hypothesize as to the implications of this on the evolution hierarchical structures such as nervous systems in larger organisms.}, } @article {pmid36893064, year = {2023}, author = {Garg, A and Nam, W and Wang, W and Vikesland, P and Zhou, W}, title = {In Situ Spatiotemporal SERS Measurements and Multivariate Analysis of Virally Infected Bacterial Biofilms Using Nanolaminated Plasmonic Crystals.}, journal = {ACS sensors}, volume = {8}, number = {3}, pages = {1132-1142}, doi = {10.1021/acssensors.2c02412}, pmid = {36893064}, issn = {2379-3694}, mesh = {*Spectrum Analysis, Raman/methods ; Multivariate Analysis ; Discriminant Analysis ; *Biofilms ; Cluster Analysis ; }, abstract = {In situ spatiotemporal biochemical characterization of the activity of living multicellular biofilms under external stimuli remains a significant challenge. Surface-enhanced Raman spectroscopy (SERS), combining the molecular fingerprint specificity of vibrational spectroscopy with the hotspot sensitivity of plasmonic nanostructures, has emerged as a promising noninvasive bioanalysis technique for living systems. However, most SERS devices do not allow reliable long-term spatiotemporal SERS measurements of multicellular systems because of challenges in producing spatially uniform and mechanically stable SERS hotspot arrays to interface with large cellular networks. Furthermore, very few studies have been conducted for multivariable analysis of spatiotemporal SERS datasets to extract spatially and temporally correlated biological information from multicellular systems. Here, we demonstrate in situ label-free spatiotemporal SERS measurements and multivariate analysis of Pseudomonas syringae biofilms during development and upon infection by bacteriophage virus Phi6 by employing nanolaminate plasmonic crystal SERS devices to interface mechanically stable, uniform, and spatially dense hotspot arrays with the P. syringae biofilms. We exploited unsupervised multivariate machine learning methods, including principal component analysis (PCA) and hierarchical cluster analysis (HCA), to resolve the spatiotemporal evolution and Phi6 dose-dependent changes of major Raman peaks originating from biochemical components in P. syringae biofilms, including cellular components, extracellular polymeric substances (EPS), metabolite molecules, and cell lysate-enriched extracellular media. We then employed supervised multivariate analysis using linear discriminant analysis (LDA) for the multiclass classification of Phi6 dose-dependent biofilm responses, demonstrating the potential for viral infection diagnosis. We envision extending the in situ spatiotemporal SERS method to monitor dynamic, heterogeneous interactions between viruses and bacterial networks for applications such as phage-based anti-biofilm therapy development and continuous pathogenic virus detection.}, } @article {pmid36877741, year = {2023}, author = {Luque, LM and Carlevaro, CM and Llamoza Torres, CJ and Lomba, E}, title = {Physics-based tissue simulator to model multicellular systems: A study of liver regeneration and hepatocellular carcinoma recurrence.}, journal = {PLoS computational biology}, volume = {19}, number = {3}, pages = {e1010920}, pmid = {36877741}, issn = {1553-7358}, mesh = {Humans ; *Carcinoma, Hepatocellular ; Liver Regeneration ; *Liver Neoplasms ; Hepatectomy ; Models, Biological ; Neoplasm Recurrence, Local ; Tumor Microenvironment ; }, abstract = {We present a multiagent-based model that captures the interactions between different types of cells with their microenvironment, and enables the analysis of the emergent global behavior during tissue regeneration and tumor development. Using this model, we are able to reproduce the temporal dynamics of regular healthy cells and cancer cells, as well as the evolution of their three-dimensional spatial distributions. By tuning the system with the characteristics of the individual patients, our model reproduces a variety of spatial patterns of tissue regeneration and tumor growth, resembling those found in clinical imaging or biopsies. In order to calibrate and validate our model we study the process of liver regeneration after surgical hepatectomy in different degrees. In the clinical context, our model is able to predict the recurrence of a hepatocellular carcinoma after a 70% partial hepatectomy. The outcomes of our simulations are in agreement with experimental and clinical observations. By fitting the model parameters to specific patient factors, it might well become a useful platform for hypotheses testing in treatments protocols.}, } @article {pmid36876435, year = {2023}, author = {Bernardo, N and Crespo, I and Cuppari, A and Meijer, WJJ and Boer, DR}, title = {A tetramerization domain in prokaryotic and eukaryotic transcription regulators homologous to p53.}, journal = {Acta crystallographica. Section D, Structural biology}, volume = {79}, number = {Pt 3}, pages = {259-267}, pmid = {36876435}, issn = {2059-7983}, support = {BIO2016-77883-C2-2-P//Ministerio de Economía y Competitividad, Agencia Estatal de Investigación/ ; PID2020-117028GB-I00//Ministerio de Economía y Competitividad, Agencia Estatal de Investigación/ ; FIS2015-72574-EXP//Ministerio de Economía y Competitividad, Agencia Estatal de Investigación/ ; PID2019-108778GB-C21//Ministerio de Economía y Competitividad, Agencia Estatal de Investigación/ ; BIO2016-77883-C2-1-P//Ministerio de Economía y Competitividad, Agencia Estatal de Investigación/ ; }, mesh = {Humans ; *Eukaryota ; Tumor Suppressor Protein p53 ; *Bacillus ; Bacillus subtilis ; Transcription Factors ; DNA ; }, abstract = {Transcriptional regulation usually requires the action of several proteins that either repress or activate a promotor of an open reading frame. These proteins can counteract each other, thus allowing tight regulation of the transcription of the corresponding genes, where tight repression is often linked to DNA looping or cross-linking. Here, the tetramerization domain of the bacterial gene repressor Rco from Bacillus subtilis plasmid pLS20 (RcopLS20) has been identified and its structure is shown to share high similarity to the tetramerization domain of the well known p53 family of human tumor suppressors, despite lacking clear sequence homology. In RcopLS20, this tetramerization domain is responsible for inducing DNA looping, a process that involves multiple tetramers. In accordance, it is shown that RcopLS20 can form octamers. This domain was named TetDloop and its occurrence was identified in other Bacillus species. The TetDloop fold was also found in the structure of a transcriptional repressor from Salmonella phage SPC32H. It is proposed that the TetDloop fold has evolved through divergent evolution and that the TetDloop originates from a common ancestor predating the occurrence of multicellular life.}, } @article {pmid36860212, year = {2022}, author = {Du, Q and Schaap, P}, title = {Autophagy of the somatic stalk cells likely nurses the propagating spores of Dictyostelid social amoebas [version 2; peer review: 2 approved, 1 approved with reservations].}, journal = {Open research Europe}, volume = {2}, number = {}, pages = {104}, pmid = {36860212}, issn = {2732-5121}, support = {742288/ERC_/European Research Council/International ; }, abstract = {BACKGROUND: Autophagy (self-feeding) assists survival of starving cells by partial self-digestion, while dormancy as cysts, spores or seeds enables long-term survival. Starving Dictyostelium amoebas construct multicellular fruiting bodies with spores and stalk cells, with many Dictyostelia still able to encyst individually like their single-celled ancestors. While autophagy mostly occurs in the somatic stalk cells, autophagy gene knock-outs in Dictyostelium discoideum (D. discoideum) formed no spores and lacked cAMP induction of prespore gene expression.

METHODS: To investigate whether autophagy also prevents encystation, we knocked-out autophagy genes atg5 and atg7 in the dictyostelid Polysphondylium pallidum, which forms both spores and cysts. We measured spore and cyst differentiation and viability in the knock-out as well as stalk and spore gene expression and its regulation by cAMP. We tested a hypothesis that spores require materials derived from autophagy in stalk cells. Sporulation requires secreted cAMP acting on receptors and intracellular cAMP acting on PKA. We compared the morphology and viability of spores developed in fruiting bodies with spores induced from single cells by stimulation with cAMP and 8Br-cAMP, a membrane-permeant PKA agonist.

RESULTS: Loss of autophagy in P. pallidum reduced but did not prevent encystation. Stalk cells still differentiated but stalks were disorganised. However, no spores were formed at all and cAMP-induced prespore gene expression was lost. D. discoideum spores induced in vitro by cAMP and 8Br-cAMP were smaller and rounder than spores formed multicellularly and while they were not lysed by detergent they germinated not (strain Ax2) or poorly (strain NC4), unlike spores formed in fruiting bodies.

CONCLUSIONS: The stringent requirement of sporulation on both multicellularity and autophagy, which occurs mostly in stalk cells, suggests that stalk cells nurse the spores through autophagy. This highlights autophagy as a major cause for somatic cell evolution in early multicellularity.}, } @article {pmid36856076, year = {2023}, author = {Takeuchi, K and Senda, M and Ikeda, Y and Okuwaki, K and Fukuzawa, K and Nakagawa, S and Sasaki, M and Sasaki, AT and Senda, T}, title = {Functional molecular evolution of a GTP sensing kinase: PI5P4Kβ.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.16763}, pmid = {36856076}, issn = {1742-4658}, support = {R01 CA255331/CA/NCI NIH HHS/United States ; R01GM144426/NH/NIH HHS/United States ; R01 NS089815/NS/NINDS NIH HHS/United States ; R01 GM144426/GM/NIGMS NIH HHS/United States ; R01CA255331/NH/NIH HHS/United States ; R01NS089815/NH/NIH HHS/United States ; }, abstract = {Over 4 billion years of evolution, multiple mutations, including nucleotide substitutions, gene and genome duplications and recombination, have established de novo genes that translate into proteins with novel properties essential for high-order cellular functions. However, molecular processes through which a protein evolutionarily acquires a novel function are mostly speculative. Recently, we have provided evidence for a potential evolutionary mechanism underlying how, in mammalian cells, phosphatidylinositol 5-phosphate 4-kinase β (PI5P4Kβ) evolved into a GTP sensor from ATP-utilizing kinase. Mechanistically, PI5P4Kβ has acquired the guanine efficient association (GEA) motif by mutating its nucleotide base recognition sequence, enabling the evolutionary transition from an ATP-dependent kinase to a distinct GTP/ATP dual kinase with its KM for GTP falling into physiological GTP concentrations-the genesis of GTP sensing activity. Importantly, the GTP sensing activity of PI5P4Kβ is critical for the manifestation of cellular metabolism and tumourigenic activity in the multicellular organism. The combination of structural, biochemical and biophysical analyses used in our study provides a novel framework for analysing how a protein can evolutionarily acquire a novel activity, which potentially introduces a critical function to the cell.}, } @article {pmid36854987, year = {2023}, author = {Duan, J and Wang, Y}, title = {Modeling nervous system tumors with human stem cells and organoids.}, journal = {Cell regeneration (London, England)}, volume = {12}, number = {1}, pages = {4}, pmid = {36854987}, issn = {2045-9769}, support = {2017YFA0106500//Stem Cell and Translational Research/ ; 2019JDJQ0029//the Distinguished Young Scientists Program of Sichuan Province/ ; ZYYC20019//the 135 Program for Excellent Scholars at West China Hospital/ ; }, abstract = {Nervous system cancers are the 10th leading cause of death worldwide, many of which are difficult to diagnose and exhibit varying degrees of treatment resistance. The limitations of existing cancer models, such as patient-derived xenograft (PDX) models and genetically engineered mouse (GEM) models, call for the development of novel preclinical cancer models to more faithfully mimic the patient's cancer and offer additional insights. Recent advances in human stem cell biology, organoid, and genome-editing techniques allow us to model nervous system tumors in three types of next-generation tumor models: cell-of-origin models, tumor organoids, and 3D multicellular coculture models. In this review, we introduced and compared different human stem cell/organoid-derived models, and comprehensively summarized and discussed the recently developed models for various primary tumors in the central and peripheral nervous systems, including glioblastoma (GBM), H3K27M-mutant Diffuse Midline Glioma (DMG) and H3G34R-mutant High-grade Glioma (HGG), Low-grade Glioma (LGG), Neurofibromatosis Type 1 (NF1), Neurofibromatosis Type 2 (NF2), Medulloblastoma (MB), Atypical Teratoid/rhabdoid Tumor (AT/RT), and meningioma. We further compared these models with PDX and GEM models, and discussed the opportunities and challenges of precision nervous cancer modeling with human stem cells and organoids.}, } @article {pmid36854263, year = {2023}, author = {Tang, S and Pichugin, Y and Hammerschmidt, K}, title = {An environmentally induced multicellular life cycle of a unicellular cyanobacterium.}, journal = {Current biology : CB}, volume = {33}, number = {4}, pages = {764-769.e5}, doi = {10.1016/j.cub.2023.01.069}, pmid = {36854263}, issn = {1879-0445}, mesh = {Animals ; *Cyanobacteria ; *Automobile Driving ; Biological Evolution ; Cell Death ; Life Cycle Stages ; }, abstract = {Understanding the evolutionary transition to multicellularity is a key problem in biology.[1][,][2][,][3][,][4] Nevertheless, the ecological conditions driving such transitions are not well understood. The first known transition to multicellularity occurred 2.5 billion years ago in cyanobacteria,[5][,][6][,][7] and today's cyanobacteria are characterized by enormous morphological diversity. They range from unicellular species; unicellular cyanobacteria with packet-like phenotypes, e.g., tetrads; and simple filamentous species to highly differentiated filamentous species.[8][,][9][,][10] The cyanobacterium Cyanothece sp. ATCC 51142, an isolate from the intertidal zone of the U.S. Gulf Coast,[11] was classified as a unicellular species.[12] We report a facultative life cycle of Cyanothece sp. in which multicellular filaments alternate with unicellular stages. In a series of experiments, we identified salinity and population density as environmental factors triggering the phenotypic switch between the two morphologies. Then, we used numerical models to test hypotheses regarding the nature of the environmental cues and the mechanisms underlying filament dissolution. While the results predict that the observed response is likely caused by an excreted compound in the medium, we cannot fully exclude changes in nutrient availability (as in Tuomi et al.[13] and Matz and Jürgens[14]). The best-fit modeling results show a nonlinear effect of the compound, which is characteristic of density-dependent sensing systems.[15][,][16] Furthermore, filament fragmentation is predicted to occur by connection cleavage rather than cell death of each alternating cell, which is supported by fluorescent and scanning electron microscopy results. The switch between unicellular and multicellular morphology constitutes an environmentally dependent life cycle that is likely an important step en route to permanent multicellularity.}, } @article {pmid36849252, year = {2023}, author = {Göbel, T and Goebel, B and Hyprath, M and Lamminger, I and Weisser, H and Angioni, C and Mathes, M and Thomas, D and Kahnt, AS}, title = {Three-dimensional growth reveals fine-tuning of 5-lipoxygenase by proliferative pathways in cancer.}, journal = {Life science alliance}, volume = {6}, number = {5}, pages = {}, pmid = {36849252}, issn = {2575-1077}, mesh = {Humans ; *Arachidonate 5-Lipoxygenase/genetics ; Lipid Metabolism ; *Colonic Neoplasms ; Mechanistic Target of Rapamycin Complex 2 ; Phosphatidylinositol 3-Kinases ; }, abstract = {The leukotriene (LT) pathway is positively correlated with the progression of solid malignancies, but the factors that control the expression of 5-lipoxygenase (5-LO), the central enzyme in LT biosynthesis, in tumors are poorly understood. Here, we report that 5-LO along with other members of the LT pathway is up-regulated in multicellular colon tumor spheroids. This up-regulation was inversely correlated with cell proliferation and activation of PI3K/mTORC-2- and MEK-1/ERK-dependent pathways. Furthermore, we found that E2F1 and its target gene MYBL2 were involved in the repression of 5-LO during cell proliferation. Importantly, we found that this PI3K/mTORC-2- and MEK-1/ERK-dependent suppression of 5-LO is also existent in tumor cells from other origins, suggesting that this mechanism is widely applicable to other tumor entities. Our data show that tumor cells fine-tune 5-LO and LT biosynthesis in response to environmental changes repressing the enzyme during proliferation while making use of the enzyme under cell stress conditions, implying that tumor-derived 5-LO plays a role in the manipulation of the tumor stroma to quickly restore cell proliferation.}, } @article {pmid36830620, year = {2023}, author = {van Oosten-Hawle, P}, title = {Organismal Roles of Hsp90.}, journal = {Biomolecules}, volume = {13}, number = {2}, pages = {}, pmid = {36830620}, issn = {2218-273X}, mesh = {Humans ; Animals ; *HSP90 Heat-Shock Proteins/metabolism ; *Molecular Chaperones/metabolism ; Signal Transduction ; Proteostasis ; Stress, Physiological ; Mammals/metabolism ; }, abstract = {Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone that assists in the maturation of many client proteins involved in cellular signal transduction. As a regulator of cellular signaling processes, it is vital for the maintenance of cellular proteostasis and adaptation to environmental stresses. Emerging research shows that Hsp90 function in an organism goes well beyond intracellular proteostasis. In metazoans, Hsp90, as an environmentally responsive chaperone, is involved in inter-tissue stress signaling responses that coordinate and safeguard cell nonautonomous proteostasis and organismal health. In this way, Hsp90 has the capacity to influence evolution and aging, and effect behavioral responses to facilitate tissue-defense systems that ensure organismal survival. In this review, I summarize the literature on the organismal roles of Hsp90 uncovered in multicellular organisms, from plants to invertebrates and mammals.}, } @article {pmid36824942, year = {2023}, author = {Compton, Z and Harris, V and Mellon, W and Rupp, S and Mallo, D and Kapsetaki, SE and Wilmot, M and Kennington, R and Noble, K and Baciu, C and Ramirez, L and Peraza, A and Martins, B and Sudhakar, S and Aksoy, S and Furukawa, G and Vincze, O and Giraudeau, M and Duke, EG and Spiro, S and Flach, E and Davidson, H and Zehnder, A and Graham, TA and Troan, B and Harrison, TM and Tollis, M and Schiffman, JD and Aktipis, A and Abegglen, LM and Maley, CC and Boddy, AM}, title = {Cancer Prevalence Across Vertebrates.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.02.15.527881}, pmid = {36824942}, abstract = {Cancer is pervasive across multicellular species. Are there any patterns that can explain differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight and decreases with gestation time, contrary to Peto’s Paradox. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer.}, } @article {pmid36822389, year = {2023}, author = {Wang, S and Chan, SY and Deng, Y and Khoo, BL and Chua, SL}, title = {Oxidative stress induced by Etoposide anti-cancer chemotherapy drives the emergence of tumor-associated bacteria resistance to fluoroquinolones.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2023.02.011}, pmid = {36822389}, issn = {2090-1224}, abstract = {INTRODUCTION: Antibiotic-resistant bacterial infections, such as Pseudomonas aeruginosa and Staphylococcus aureus, are prevalent in lung cancer patients, resulting in poor clinical outcomes and high mortality. Etoposide (ETO) is an FDA-approved chemotherapy drug that kills cancer cells by damaging DNA through oxidative stress. However, it is unclear if ETO can cause unintentional side effects on tumor-associated microbial pathogens, such as inducing antibiotic resistance.

OBJECTIVES: We aimed to show that prolonged ETO treatment could unintendedly confer fluoroquinolone antibiotic resistance to P. aeruginosa, and evaluate the effect of tumor-associated P. aeruginosa on tumor progression.

METHODS: We employed experimental evolution assay to treat P. aeruginosa with prolonged ETO exposure, evaluated the ciprofloxacin resistance, and elucidated the gene mutations by DNA sequencing. We also established a lung tumor-P. aeruginosa bacterial model to study the role of ETO-evolved intra-tumoral bacteria in tumor progression using immunostaining and confocal microscopy.

RESULTS: ETO could generate oxidative stress and lead to gene mutations in P. aeruginosa, especially the gyrase (gyrA) gene, resulting in acquired fluoroquinolone resistance. We further demonstrated using a microfluidic-based lung tumor-P. aeruginosa coculture model that bacteria can evolve ciprofloxacin (CIP) resistance in a tumor microenvironment. Moreover, ETO-induced CIP-resistant (EICR) mutants could form multicellular biofilms which protected tumor cells from ETO killing and enabled tumor progression.

CONCLUSION: Overall, our preclinical proof-of-concept provides insights into how anti-cancer chemotherapy could inadvertently allow tumor-associated bacteria to acquire antibiotic resistance mutations and shed new light on the development of novel anti-cancer treatments based on anti-bacterial strategies.}, } @article {pmid36821408, year = {2023}, author = {Baselga-Cervera, B and Jacobsen, KA and Ford Denison, R and Travisano, M}, title = {Experimental evolution in the cyanobacterium Trichormus variabilis: increases in size and morphological diversity.}, journal = {Evolution; international journal of organic evolution}, volume = {77}, number = {5}, pages = {1216-1225}, doi = {10.1093/evolut/qpad037}, pmid = {36821408}, issn = {1558-5646}, mesh = {*Anabaena variabilis ; *Anabaena/genetics ; }, abstract = {Cyanobacteria morphology has apparently remained almost unchanged for billions of years, exhibiting remarkable evolutionary stasis. Cyanobacteria appear to have reached their maximum morphological complexity in terms of size, modes of multicellularity, and cellular types by ~2 Ga. This contrasts with the increased complexity observed in other multicellular lineages, such as plants. Using experimental evolution, we show that morphological diversity can rapidly evolve in a species of filamentous cyanobacteria. Since size has such significance with regard to organismal complexity, we subjected the heterocyst-forming cyanobacterium Trichornus variabilis (syn. Anabaena variabilis) to selection for larger size. We observed increases in size of more than 30-fold, relative to the ancestral population, after 45 cycles of selection. Two distinguishable nascent morphological elaborations were identified in all the selected populations: Tangle (long, tangled filaments) and Cluster (clusters of short filaments) morphology. Growth from single cells indicates heritability of the evolved Tangle and Cluster morphological phenotypes. Cyanobacteria evolutionary conservatism is ascribed to developmental constraints, slow evolution rates, or ecological flexibility. These results open opportunities to study possibilities and constraints for the evolution of higher integrated biological levels of organization within this lineage.}, } @article {pmid36816026, year = {2023}, author = {Horjales, S and Li Calzi, M and Francia, ME and Cayota, A and Garcia-Silva, MR}, title = {piRNA pathway evolution beyond gonad context: Perspectives from apicomplexa and trypanosomatids.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1129194}, pmid = {36816026}, issn = {1664-8021}, abstract = {piRNAs function as genome defense mechanisms against transposable elements insertions within germ line cells. Recent studies have unraveled that piRNA pathways are not limited to germ cells as initially reckoned, but are instead also found in non-gonadal somatic contexts. Moreover, these pathways have also been reported in bacteria, mollusks and arthropods, associated with safeguard of genomes against transposable elements, regulation of gene expression and with direct consequences in axon regeneration and memory formation. In this Perspective we draw attention to early branching parasitic protozoa, whose genome preservation is an essential function as in late eukaryotes. However, little is known about the defense mechanisms of these genomes. We and others have described the presence of putative PIWI-related machinery members in protozoan parasites. We have described the presence of a PIWI-like protein in Trypanosoma cruzi, bound to small non-coding RNAs (sRNAs) as cargo of secreted extracellular vesicles relevant in intercellular communication and host infection. Herein, we put forward the presence of members related to Argonaute pathways in both Trypanosoma cruzi and Toxoplasma gondii. The presence of PIWI-like machinery in Trypansomatids and Apicomplexa, respectively, could be evidence of an ancestral piRNA machinery that evolved to become more sophisticated and complex in multicellular eukaryotes. We propose a model in which ancient PIWI proteins were expressed broadly and had functions independent of germline maintenance. A better understanding of current and ancestral PIWI/piRNAs will be relevant to better understand key mechanisms of genome integrity conservation during cell cycle progression and modulation of host defense mechanisms by protozoan parasites.}, } @article {pmid36813362, year = {2023}, author = {Samuel, V and Rajeev, T and Ramesh, L and Sundararaman, A}, title = {Integrin receptor trafficking in health and disease.}, journal = {Progress in molecular biology and translational science}, volume = {196}, number = {}, pages = {271-302}, doi = {10.1016/bs.pmbts.2022.09.008}, pmid = {36813362}, issn = {1878-0814}, mesh = {Humans ; Protein Transport/physiology ; *Integrins/metabolism ; Cell Membrane/metabolism ; Signal Transduction ; *Neoplasms/metabolism ; Cell Adhesion/physiology ; Cell Movement/physiology ; }, abstract = {Integrins are a family of 24 different heterodimers that are indispensable for multicellular life. Cell polarity, adhesion and migration are controlled by integrins delivered to the cell surface which in turn is regulated by the exo- and endocytic trafficking of integrins. The deep integration between trafficking and cell signaling determines the spatial and temporal output from any biochemical cue. Integrin trafficking plays a key role in development and many pathological conditions, especially cancer. Several novel regulators of integrin traffic have been discovered in recent times, including a novel class of integrin carrying vesicles, the intracellular nanovesicles (INVs). The tight regulation of trafficking pathways by cell signaling, where kinases phosphorylate key small GTPases in the trafficking pathway enable coordination of cell response to the extracellular milieu. Integrin heterodimer expression and trafficking differ in different tissues and contexts. In this Chapter, we discuss recent studies on integrin trafficking and its contribution to normal physiological and pathophysiological states.}, } @article {pmid36811171, year = {2023}, author = {Furumizu, C and Aalen, RB}, title = {Peptide signaling through leucine-rich repeat receptor kinases: insight into land plant evolution.}, journal = {The New phytologist}, volume = {238}, number = {3}, pages = {977-982}, doi = {10.1111/nph.18827}, pmid = {36811171}, issn = {1469-8137}, mesh = {*Protein Serine-Threonine Kinases/metabolism ; Plant Proteins/metabolism ; Leucine ; Phylogeny ; Signal Transduction/physiology ; Peptides/genetics ; *Embryophyta/genetics/metabolism ; }, abstract = {Multicellular organisms need mechanisms for communication between cells so that they can fulfill their purpose in the organism as a whole. Over the last two decades, several small post-translationally modified peptides (PTMPs) have been identified as components of cell-to-cell signaling modules in flowering plants. Such peptides most often influence growth and development of organs not universally conserved among land plants. PTMPs have been matched to subfamily XI leucine-rich repeat receptor-like kinases with > 20 repeats. Phylogenetic analyses, facilitated by recently published genomic sequences of non-flowering plants, have identified seven clades of such receptors with a history back to the common ancestor of bryophytes and vascular plants. This raises a number of questions: When did peptide signaling arise during land plant evolution? Have orthologous peptide-receptor pairs preserved their biological functions? Has peptide signaling contributed to major innovations, such as stomata, vasculature, roots, seeds, and flowers? Using genomic, genetic, biochemical, and structural data and non-angiosperm model species, it is now possible to address these questions. The vast number of peptides that have not yet found their partners suggests furthermore that we have far more to learn about peptide signaling in the coming decades.}, } @article {pmid36809239, year = {2023}, author = {Lambros, M and Sella, Y and Bergman, A}, title = {Phenotypic pliancy and the breakdown of epigenetic polycomb mechanisms.}, journal = {PLoS computational biology}, volume = {19}, number = {2}, pages = {e1010889}, pmid = {36809239}, issn = {1553-7358}, support = {R01 CA164468/CA/NCI NIH HHS/United States ; R01 DA033788/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; Polycomb-Group Proteins/genetics ; *Drosophila Proteins/metabolism ; Epigenesis, Genetic ; Cell Differentiation ; *Neoplasms/genetics ; Phenotype ; }, abstract = {Epigenetic regulatory mechanisms allow multicellular organisms to develop distinct specialized cell identities despite having the same total genome. Cell-fate choices are based on gene expression programs and environmental cues that cells experience during embryonic development, and are usually maintained throughout the life of the organism despite new environmental cues. The evolutionarily conserved Polycomb group (PcG) proteins form Polycomb Repressive Complexes that help orchestrate these developmental choices. Post-development, these complexes actively maintain the resulting cell fate, even in the face of environmental perturbations. Given the crucial role of these polycomb mechanisms in providing phenotypic fidelity (i.e. maintenance of cell fate), we hypothesize that their dysregulation after development will lead to decreased phenotypic fidelity allowing dysregulated cells to sustainably switch their phenotype in response to environmental changes. We call this abnormal phenotypic switching phenotypic pliancy. We introduce a general computational evolutionary model that allows us to test our systems-level phenotypic pliancy hypothesis in-silico and in a context-independent manner. We find that 1) phenotypic fidelity is an emergent systems-level property of PcG-like mechanism evolution, and 2) phenotypic pliancy is an emergent systems-level property resulting from this mechanism's dysregulation. Since there is evidence that metastatic cells behave in a phenotypically pliant manner, we hypothesize that progression to metastasis is driven by the emergence of phenotypic pliancy in cancer cells as a result of PcG mechanism dysregulation. We corroborate our hypothesis using single-cell RNA-sequencing data from metastatic cancers. We find that metastatic cancer cells are phenotypically pliant in the same manner as predicted by our model.}, } @article {pmid36806172, year = {2023}, author = {Kuang, X and Guan, G and Tang, C and Zhang, L}, title = {MorphoSim: an efficient and scalable phase-field framework for accurately simulating multicellular morphologies.}, journal = {NPJ systems biology and applications}, volume = {9}, number = {1}, pages = {6}, pmid = {36806172}, issn = {2056-7189}, support = {12225102//National Natural Science Foundation of China (National Science Foundation of China)/ ; 12050002//National Natural Science Foundation of China (National Science Foundation of China)/ ; 12090053//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32088101//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {The phase field model can accurately simulate the evolution of microstructures with complex morphologies, and it has been widely used for cell modeling in the last two decades. However, compared to other cellular models such as the coarse-grained model and the vertex model, its high computational cost caused by three-dimensional spatial discretization hampered its application and scalability, especially for multicellular organisms. Recently, we built a phase field model coupled with in vivo imaging data to accurately reconstruct the embryonic morphogenesis of Caenorhabditis elegans from 1- to 8-cell stages. In this work, we propose an improved phase field model by using the stabilized numerical scheme and modified volume constriction. Then we present a scalable phase-field framework, MorphoSim, which is 100 times more efficient than the previous one and can simulate over 100 mechanically interacting cells. Finally, we demonstrate how MorphoSim can be successfully applied to reproduce the assembly, self-repairing, and dissociation of a synthetic artificial multicellular system - the synNotch system.}, } @article {pmid36797913, year = {2023}, author = {Leptos, KC and Chioccioli, M and Furlan, S and Pesci, AI and Goldstein, RE}, title = {Phototaxis of Chlamydomonas arises from a tuned adaptive photoresponse shared with multicellular Volvocine green algae.}, journal = {Physical review. E}, volume = {107}, number = {1-1}, pages = {014404}, doi = {10.1103/PhysRevE.107.014404}, pmid = {36797913}, issn = {2470-0053}, support = {207510/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Chlamydomonas ; Phylogeny ; Phototaxis ; *Chlorophyta ; Biological Evolution ; *Volvox ; }, abstract = {A fundamental issue in biology is the nature of evolutionary transitions from unicellular to multicellular organisms. Volvocine algae are models for this transition, as they span from the unicellular biflagellate Chlamydomonas to multicellular species of Volvox with up to 50,000 Chlamydomonas-like cells on the surface of a spherical extracellular matrix. The mechanism of phototaxis in these species is of particular interest since they lack a nervous system and intercellular connections; steering is a consequence of the response of individual cells to light. Studies of Volvox and Gonium, a 16-cell organism with a plate-like structure, have shown that the flagellar response to changing illumination of the cellular photosensor is adaptive, with a recovery time tuned to the rotation period of the colony around its primary axis. Here, combining high-resolution studies of the flagellar photoresponse of micropipette-held Chlamydomonas with 3D tracking of freely swimming cells, we show that such tuning also underlies its phototaxis. A mathematical model is developed based on the rotations around an axis perpendicular to the flagellar beat plane that occur through the adaptive response to oscillating light levels as the organism spins. Exploiting a separation of timescales between the flagellar photoresponse and phototurning, we develop an equation of motion that accurately describes the observed photoalignment. In showing that the adaptive timescales in Volvocine algae are tuned to the organisms' rotational periods across three orders of magnitude in cell number, our results suggest a unified picture of phototaxis in green algae in which the asymmetry in torques that produce phototurns arise from the individual flagella of Chlamydomonas, the flagellated edges of Gonium, and the flagellated hemispheres of Volvox.}, } @article {pmid36789784, year = {2023}, author = {Rusin, LY}, title = {Evolution of homology: From archetype towards a holistic concept of cell type.}, journal = {Journal of morphology}, volume = {284}, number = {4}, pages = {e21569}, doi = {10.1002/jmor.21569}, pmid = {36789784}, issn = {1097-4687}, mesh = {Animals ; *Biological Evolution ; Phylogeny ; *Growth and Development ; Cell Lineage ; Phenotype ; }, abstract = {The concept of homology lies in the heart of comparative biological science. The distinction between homology as structure and analogy as function has shaped the evolutionary paradigm for a century and formed the axis of comparative anatomy and embryology, which accept the identity of structure as a ground measure of relatedness. The advent of single-cell genomics overturned the classical view of cell homology by establishing a backbone regulatory identity of cell types, the basic biological units bridging the molecular and phenotypic dimensions, to reveal that the cell is the most flexible unit of living matter and that many approaches of classical biology need to be revised to understand evolution and diversity at the cellular level. The emerging theory of cell types explicitly decouples cell identity from phenotype, essentially allowing for the divergence of evolutionarily related morphotypes beyond recognition, as well as it decouples ontogenetic cell lineage from cell-type phylogeny, whereby explicating that cell types can share common descent regardless of their structure, function or developmental origin. The article succinctly summarizes current progress and opinion in this field and formulates a more generalistic view of biological cell types as avatars, transient or terminal cell states deployed in a continuum of states by the developmental programme of one and the same omnipotent cell, capable of changing or combining identities with distinct evolutionary histories or inventing ad hoc identities that never existed in evolution or development. It highlights how the new logic grounded in the regulatory nature of cell identity transforms the concepts of cell homology and phenotypic stability, suggesting that cellular evolution is inherently and massively network-like, with one-to-one homologies being rather uncommon and restricted to shallower levels of the animal tree of life.}, } @article {pmid36786569, year = {2023}, author = {Cont, A and Vermeil, J and Persat, A}, title = {Material Substrate Physical Properties Control Pseudomonas aeruginosa Biofilm Architecture.}, journal = {mBio}, volume = {14}, number = {2}, pages = {e0351822}, pmid = {36786569}, issn = {2150-7511}, mesh = {Humans ; *Pseudomonas aeruginosa/genetics ; Biofilms ; Anti-Bacterial Agents/pharmacology ; *Pseudomonas Infections/microbiology ; }, abstract = {In the wild, bacteria are most frequently found in the form of multicellular structures called biofilms. Biofilms grow at the surface of abiotic and living materials with wide-ranging mechanical properties. The opportunistic pathogen Pseudomonas aeruginosa forms biofilms on indwelling medical devices and on soft tissues, including burn wounds and the airway mucosa. Despite the critical role of substrates in the foundation of biofilms, we still lack a clear understanding of how material mechanics regulate their architecture and the physiology of resident bacteria. Here, we demonstrate that physical properties of hydrogel material substrates define P. aeruginosa biofilm architecture. We show that hydrogel mesh size regulates twitching motility, a surface exploration mechanism priming biofilms, ultimately controlling the organization of single cells in the multicellular community. The resulting architectural transitions increase P. aeruginosa's tolerance to colistin, a last-resort antibiotic. In addition, mechanical regulation of twitching motility affects P. aeruginosa clonal lineages, so that biofilms are more mixed on relatively denser materials. Our results thereby establish material properties as a factor that dramatically affects biofilm architecture, antibiotic efficacy, and evolution of the resident population. IMPORTANCE The biofilm lifestyle is the most widespread survival strategy in the bacterial world. Pseudomonas aeruginosa biofilms cause chronic infections and are highly recalcitrant to antimicrobials. The genetic requirements allowing P. aeruginosa to grow into biofilms are known, but not the physical stimuli that regulate their formation. Despite colonizing biological tissues, investigations of biofilms on soft materials are limited. In this work, we show that biofilms take unexpected forms when growing on soft substrates. The physical properties of the material shape P. aeruginosa biofilms by regulating surface-specific twitching motility. Physical control of biofilm morphogenesis ultimately influences the resilience of biofilms to antimicrobials, linking physical environment with tolerance to treatment. Altogether, our work established that the physical properties of a surface are a critical environmental regulator of biofilm biogenesis and evolution.}, } @article {pmid36786333, year = {2023}, author = {Godfroy, O and Zheng, M and Yao, H and Henschen, A and Peters, AF and Scornet, D and Colin, S and Ronchi, P and Hipp, K and Nagasato, C and Motomura, T and Cock, JM and Coelho, SM}, title = {The baseless mutant links protein phosphatase 2A with basal cell identity in the brown alga Ectocarpus.}, journal = {Development (Cambridge, England)}, volume = {150}, number = {4}, pages = {}, pmid = {36786333}, issn = {1477-9129}, support = {//Centre National de la Recherche Scientifique/ ; //Sorbonne Université/ ; //Max Planck Society/ ; 864038/ERC_/European Research Council/International ; 201608310119//China Scholarship Council/ ; }, mesh = {*Protein Phosphatase 2/genetics/metabolism ; Mutation/genetics ; Gene Expression Profiling ; Protein Processing, Post-Translational ; *Phaeophyta/genetics/metabolism ; }, abstract = {The first mitotic division of the initial cell is a key event in all multicellular organisms and is associated with the establishment of major developmental axes and cell fates. The brown alga Ectocarpus has a haploid-diploid life cycle that involves the development of two multicellular generations: the sporophyte and the gametophyte. Each generation deploys a distinct developmental programme autonomously from an initial cell, the first cell division of which sets up the future body pattern. Here, we show that mutations in the BASELESS (BAS) gene result in multiple cellular defects during the first cell division and subsequent failure to produce basal structures during both generations. BAS encodes a type B″ regulatory subunit of protein phosphatase 2A (PP2A), and transcriptomic analysis identified potential effector genes that may be involved in determining basal cell fate. The bas mutant phenotype is very similar to that observed in distag (dis) mutants, which lack a functional Tubulin-binding co-factor Cd1 (TBCCd1) protein, indicating that TBCCd1 and PP2A are two essential components of the cellular machinery that regulates the first cell division and mediates basal cell fate determination.}, } @article {pmid36781087, year = {2023}, author = {Brown, Y and Hua, S and Tanwar, PS}, title = {Extracellular matrix in high-grade serous ovarian cancer: Advances in understanding of carcinogenesis and cancer biology.}, journal = {Matrix biology : journal of the International Society for Matrix Biology}, volume = {118}, number = {}, pages = {16-46}, doi = {10.1016/j.matbio.2023.02.004}, pmid = {36781087}, issn = {1569-1802}, mesh = {Female ; Humans ; *Ovarian Neoplasms/genetics ; *Cystadenocarcinoma, Serous/genetics ; Extracellular Matrix/pathology ; Carcinogenesis/genetics ; Biology ; Tumor Microenvironment ; }, abstract = {High-grade serous ovarian cancer (HGSOC) is notoriously known as the "silent killer" of post-menopausal women as it has an insidious progression and is the deadliest gynaecological cancer. Although a dual origin of HGSOC is now widely accepted, there is growing evidence that most cases of HGSOC originate from the fallopian tube epithelium. In this review, we will address the fallopian tube origin and involvement of the extracellular matrix (ECM) in HGSOC development. There is limited research on the role of ECM at the earliest stages of HGSOC carcinogenesis. Here we aim to synthesise current understanding of the contribution of ECM to each stage of HGSOC development and progression, beginning at serous tubal intraepithelial carcinoma (STIC) precursor lesions and proceeding across key events including dissemination of tumourigenic fallopian tube epithelial cells to the ovary, survival of these cells in peritoneal fluid as multicellular aggregates, and colonisation of the ovary. Likewise, as part of the metastatic series of events, serous ovarian cancer cells survive travel in peritoneal fluid, attach to, migrate across the mesothelium and invade into the sub-mesothelial matrix of secondary sites in the peritoneal cavity. Halting cancer at the pre-metastatic stage and finding ways to stop the dissemination of ovarian cancer cells from the primary site is critical for improving patient survival. The development of drug resistance also contributes to poor survival statistics in HGSOC. In this review, we provide an update on the involvement of the ECM in metastasis and drug resistance in HGSOC. Interplay between different cell-types, growth factor gradients as well as evolving ECM composition and organisation, creates microenvironment conditions that promote metastatic progression and drug resistance of ovarian cancer cells. By understanding ECM involvement in the carcinogenesis and chemoresistance of HGSOC, this may prompt ideas for further research for developing new early diagnostic tests and therapeutic strategies for HGSOC with the end goal of improving patient health outcomes.}, } @article {pmid36779552, year = {2023}, author = {Mitchell, RL and Kenrick, P and Pressel, S and Duckett, J and Strullu-Derrien, C and Davies, N and McMahon, WJ and Summerfield, R}, title = {Terrestrial surface stabilisation by modern analogues of the earliest land plants: A multi-dimensional imaging study.}, journal = {Geobiology}, volume = {21}, number = {4}, pages = {454-473}, doi = {10.1111/gbi.12546}, pmid = {36779552}, issn = {1472-4669}, mesh = {*Ecosystem ; *Embryophyta ; Plants ; Fungi ; Fossils ; Phylogeny ; }, abstract = {The evolution of the first plant-based terrestrial ecosystems in the early Palaeozoic had a profound effect on the development of soils, the architecture of sedimentary systems, and shifts in global biogeochemical cycles. In part, this was due to the evolution of complex below-ground (root-like) anchorage systems in plants, which expanded and promoted plant-mineral interactions, weathering, and resulting surface sediment stabilisation. However, little is understood about how these micro-scale processes occurred, because of a lack of in situ plant fossils in sedimentary rocks/palaeosols that exhibit these interactions. Some modern plants (e.g., liverworts, mosses, lycophytes) share key features with the earliest land plants; these include uni- or multicellular rhizoid-like anchorage systems or simple roots, and the ability to develop below-ground networks through prostrate axes, and intimate associations with fungi, making them suitable analogues. Here, we investigated cryptogamic ground covers in Iceland and New Zealand to better understand these interactions, and how they initiate the sediment stabilisation process. We employed multi-dimensional and multi-scale imaging, including scanning electron microscopy (SEM) and X-ray Computed Tomography (μCT) of non-vascular liverworts (Haplomitriopsida and complex thalloids) and mosses, with additional imaging of vascular lycopods. We find that plants interact with their substrate in multiple ways, including: (1) through the development of extensive surface coverings as mats; (2) entrapment of sediment grains within and between networks of rhizoids; (3) grain entwining and adherence by rhizoids, through mucilage secretions, biofilm-like envelopment of thalli on surface grains; and (4) through grain entrapment within upright 'leafy' structures. Significantly, μCT imaging allows us to ascertain that rhizoids are the main method for entrapment and stabilisation of soil grains in the thalloid liverworts. This information provides us with details of how the earliest land plants may have significantly influenced early Palaeozoic sedimentary system architectures, promoted in situ weathering and proto-soil development, and how these interactions diversified over time with the evolution of new plant organ systems. Further, this study highlights the importance of cryptogamic organisms in the early stages of sediment stabilisation and soil formation today.}, } @article {pmid36778228, year = {2023}, author = {Feng, X and Zheng, J and Irisarri, I and Yu, H and Zheng, B and Ali, Z and de Vries, S and Keller, J and Fürst-Jansen, JMR and Dadras, A and Zegers, JMS and Rieseberg, TP and Ashok, AD and Darienko, T and Bierenbroodspot, MJ and Gramzow, L and Petroll, R and Haas, FB and Fernandez-Pozo, N and Nousias, O and Li, T and Fitzek, E and Grayburn, WS and Rittmeier, N and Permann, C and Rümpler, F and Archibald, JM and Theißen, G and Mower, JP and Lorenz, M and Buschmann, H and von Schwartzenberg, K and Boston, L and Hayes, RD and Daum, C and Barry, K and Grigoriev, IV and Wang, X and Li, FW and Rensing, SA and Ari, JB and Keren, N and Mosquna, A and Holzinger, A and Delaux, PM and Zhang, C and Huang, J and Mutwil, M and de Vries, J and Yin, Y}, title = {Chromosome-level genomes of multicellular algal sisters to land plants illuminate signaling network evolution.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36778228}, abstract = {UNLABELLED: The filamentous and unicellular algae of the class Zygnematophyceae are the closest algal relatives of land plants. Inferring the properties of the last common ancestor shared by these algae and land plants allows us to identify decisive traits that enabled the conquest of land by plants. We sequenced four genomes of filamentous Zygnematophyceae (three strains of Zygnema circumcarinatum and one strain of Z. cylindricum) and generated chromosome-scale assemblies for all strains of the emerging model system Z. circumcarinatum . Comparative genomic analyses reveal expanded genes for signaling cascades, environmental response, and intracellular trafficking that we associate with multicellularity. Gene family analyses suggest that Zygnematophyceae share all the major enzymes with land plants for cell wall polysaccharide synthesis, degradation, and modifications; most of the enzymes for cell wall innovations, especially for polysaccharide backbone synthesis, were gained more than 700 million years ago. In Zygnematophyceae, these enzyme families expanded, forming co-expressed modules. Transcriptomic profiling of over 19 growth conditions combined with co-expression network analyses uncover cohorts of genes that unite environmental signaling with multicellular developmental programs. Our data shed light on a molecular chassis that balances environmental response and growth modulation across more than 600 million years of streptophyte evolution.

HIGHLIGHTS: Genomes of four filamentous algae (Zygnema) sisters to land plants Zygnema are rich in genes for multicellular growth and environmental acclimation: signaling, lipid modification, and transport Cell wall innovations: diversification of hexameric rosette cellulose synthase in ZygnematophyceaeCo-expression networks reveal conserved modules for balancing growth and acclimation.}, } @article {pmid36765079, year = {2023}, author = {Debit, A and Charton, F and Pierre-Elies, P and Bowler, C and Cruz de Carvalho, H}, title = {Differential expression patterns of long noncoding RNAs in a pleiomorphic diatom and relation to hyposalinity.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2440}, pmid = {36765079}, issn = {2045-2322}, mesh = {Animals ; *Diatoms/metabolism ; *RNA, Long Noncoding/genetics/metabolism ; Gene Expression Profiling ; Transcriptome ; Culture Media/metabolism ; }, abstract = {Long non-coding (lnc)RNAs have been shown to have central roles in stress responses, cell identity and developmental processes in multicellular organisms as well as in unicellular fungi. Previous works have shown the occurrence of lncRNAs in diatoms, namely in Phaeodactylum tricornutum, many of which being expressed under specific stress conditions. Interestingly, P. tricornutum is the only known diatom that has a demonstrated morphological plasticity, occurring in three distinct morphotypes: fusiform, triradiate and oval. Although the morphotypes are interchangeable, the fusiform is the dominant one while both the triradiate and the oval forms are less common, the latter often being associated with stress conditions such as low salinity and solid culture media, amongst others. Nonetheless, the molecular basis underpinning morphotype identity in P. tricornutum remains elusive. Using twelve previously published transcriptomic datasets originating from the three morphotypes of P. tricornutum, we sought to investigate the expression patterns of lncRNAs (lincRNAs and NATs) in these distinct morphotypes, using pairwise comparisons, in order to explore the putative involvement of these noncoding molecules in morphotype identity. We found that differentially expressed lncRNAs cluster according to morphotype, indicating that lncRNAs are not randomly expressed, but rather seem to provide a specific (noncoding) transcriptomic signature of the morphotype. We also present evidence to suggest that the major differences in DE genes (both noncoding and coding) between the stress related oval morphotype and the most common fusiform morphotype could be due, to a large extent, to the hyposaline culture conditions rather than to the morphotype itself. However, several lncRNAs associated to each one of the three morphotypes were identified, which could have a potential role in morphotype (or cell) identity in P. tricornutum, similar to what has been found in both animals and plant development.}, } @article {pmid36756235, year = {2022}, author = {Yang, Q and Sharif, Y and Zhuang, Y and Chen, H and Zhang, C and Fu, H and Wang, S and Cai, T and Chen, K and Raza, A and Wang, L and Zhuang, W}, title = {Genome-wide identification of germin-like proteins in peanut (Arachis hypogea L.) and expression analysis under different abiotic stresses.}, journal = {Frontiers in plant science}, volume = {13}, number = {}, pages = {1044144}, pmid = {36756235}, issn = {1664-462X}, abstract = {Peanut is an important food and feed crop, providing oil and protein nutrients. Germins and germin-like proteins (GLPs) are ubiquitously present in plants playing numerous roles in defense, growth and development, and different signaling pathways. However, the GLP members have not been comprehensively studied in peanut at the genome-wide scale. We carried out a genome-wide identification of the GLP genes in peanut genome. GLP members were identified comprehensively, and gene structure, genomic positions, motifs/domains distribution patterns, and phylogenetic history were studied in detail. Promoter Cis-elements, gene duplication, collinearity, miRNAs, protein-protein interactions, and expression were determined. A total of 84 GLPs (AhGLPs) were found in the genome of cultivated peanut. These GLP genes were clustered into six groups. Segmental duplication events played a key role in the evolution of AhGLPs, and purifying selection pressure was underlying the duplication process. Most AhGLPs possessed a well-maintained gene structure and motif organization within the same group. The promoter regions of AhGLPs contained several key cis-elements responsive to 'phytohormones', 'growth and development', defense, and 'light induction'. Seven microRNAs (miRNAs) from six families were found targeting 25 AhGLPs. Gene Ontology (GO) enrichment analysis showed that AhGLPs are highly enriched in nutrient reservoir activity, aleurone grain, external encapsulating structure, multicellular organismal reproductive process, and response to acid chemicals, indicating their important biological roles. AhGLP14, AhGLP38, AhGLP54, and AhGLP76 were expressed in most tissues, while AhGLP26, AhGLP29, and AhGLP62 showed abundant expression in the pericarp. AhGLP7, AhGLP20, and AhGLP21, etc., showed specifically high expression in embryo, while AhGLP12, AhGLP18, AhGLP40, AhGLP78, and AhGLP82 were highly expressed under different hormones, water, and temperature stress. The qRT-PCR results were in accordance with the transcriptome expression data. In short, these findings provided a foundation for future functional investigations on the AhGLPs for peanut breeding programs.}, } @article {pmid36750954, year = {2023}, author = {Zhang, X and Chen, S and Zhao, Z and Ma, C and Liu, Y}, title = {Investigation of B-atp6-orfH79 distributing in Chinese populations of Oryza rufipogon and analysis of its chimeric structure.}, journal = {BMC plant biology}, volume = {23}, number = {1}, pages = {81}, pmid = {36750954}, issn = {1471-2229}, mesh = {DNA, Mitochondrial/genetics/metabolism ; Mitochondria/metabolism ; *Oryza/genetics ; Plant Breeding ; }, abstract = {BACKGROUND: The cytoplasmic male sterility (CMS) of rice is caused by chimeric mitochondrial DNA (mtDNA) that is maternally inherited in the majority of multicellular organisms. Wild rice (Oryza rufipogon Griff.) has been regarded as the ancestral progenitor of Asian cultivated rice (Oryza sativa L.). To investigate the distribution of original CMS source, and explore the origin of gametophytic CMS gene, a total of 427 individuals with seventeen representative populations of O. rufipogon were collected in from Dongxiang of Jiangxi Province to Sanya of Hainan Province, China, for the PCR amplification of atp6, orfH79 and B-atp6-orfH79, respectively.

RESULTS: The B-atp6-orfH79 and its variants (B-atp6-GSV) were detected in five among seventeen populations (i.e. HK, GZ, PS, TL and YJ) through PCR amplification, which could be divided into three haplotypes, i.e., BH1, BH2, and BH3. The BH2 haplotype was identical to B-atp6-orfH79, while the BH1 and BH3 were the novel haplotypes of B-atp6-GSV. Combined with the high-homology sequences in GenBank, a total of eighteen haplotypes have been revealed, only with ten haplotypes in orfH79 and its variants (GSV) that belong to three species (i.e. O. rufipogon, Oryza nivara and Oryza sativa). Enough haplotypes clearly demonstrated the uniform structural characteristics of the B-atp6-orfH79 as follows: except for the conserved sequence (671 bp) composed of B-atp6 (619 bp) and the downstream followed the B-atp6 (52 bp, DS), and GSV sequence, a rich variable sequence (VS, 176 bp) lies between the DS and GSV with five insertion or deletion and more than 30 single nucleotide polymorphism. Maximum likelihood analysis showed that eighteen haplotypes formed three clades with high support rate. The hierarchical analysis of molecular variance (AMOVA) indicated the occurrence of variation among all populations (FST = 1; P < 0.001), which implied that the chimeric structure occurred independently. Three haplotypes (i.e., H1, H2 and H3) were detected by the primer of orfH79, which were identical to the GVS in B-atp6-GVS structure, respectively. All seventeen haplotypes of the orfH79, belonged to six species based on our results and the existing references. Seven existed single nucleotide polymorphism in GSV section can be translated into eleven various amino acid sequences.

CONCLUSIONS: Generally, this study, indicating that orfH79 was always accompanied by the B-atp6, not only provide two original CMS sources for rice breeding, but also confirm the uniform structure of B-atp-orfH79, which contribute to revealing the origin of rice gametophytic CMS genes, and the reason about frequent recombination of mitochondrial DNA.}, } @article {pmid36743469, year = {2023}, author = {Liu, J and Xing, WY and Liu, B and Zhang, CC}, title = {Three-dimensional coordination of cell-division site positioning in a filamentous cyanobacterium.}, journal = {PNAS nexus}, volume = {2}, number = {2}, pages = {pgac307}, pmid = {36743469}, issn = {2752-6542}, abstract = {Bacterial cells mostly divide symmetrically. In the filamentous, multicellular cyanobacterium Anabaena, cell-division planes are aligned vertically relative to the long axis of every single cell. This observation suggests that both the placement and the angle of the division planes are controlled in every single cell so that the filament can grow in one single dimension along the long axis. In this study, we showed that inactivation of patU3 encoding a cell-division inhibitor led cells to divide asymmetrically in two dimensions leading to twisted filaments, indicating that PatU3 controls not only the position but also the angle of the division planes. Deletion of the conserved minC and minD genes affected cell division symmetry, but not the angle of the division planes. Remarkably, when both patU3 and minCD were inactivated, cells could divide asymmetrically over 360° angles in three dimensions across different cellular sections, producing not only cells with irregular sizes, but also branching filaments. This study demonstrated the existence of a system operating in a three-dimensional manner for the control of cell division in Anabaena. Such a regulation may have been evolved to accommodate multicellular behaviors, a hallmark in evolution.}, } @article {pmid36717890, year = {2023}, author = {Piccinini, G and Milani, L}, title = {Germline-related molecular phenotype in Metazoa: conservation and innovation highlighted by comparative transcriptomics.}, journal = {EvoDevo}, volume = {14}, number = {1}, pages = {2}, pmid = {36717890}, issn = {2041-9139}, abstract = {BACKGROUND: In Metazoa, the germline represents the cell lineage devoted to the transmission of genetic heredity across generations. Its functions intuitively evoke the crucial roles that it plays in organism development and species evolution, and its establishment is tightly tied to animal multicellularity itself. The molecular toolkit expressed in germ cells has a high degree of conservation between species, and it also shares many components with the molecular phenotype of some animal totipotent cell lineages, like planarian neoblasts and sponge archaeocytes. The present study stems from these observations and represents a transcriptome-wide comparative analysis between germline-related samples of 9 animal species (7 phyla), comprehending also totipotent lineages classically considered somatic.

RESULTS: Differential expression analyses were performed for each species between germline-related and control somatic tissues. We then compared the different germline-related transcriptional profiles across the species without the need for an a priori set of genes. Through a phylostratigraphic analysis, we observed that the proportion of phylum- and Metazoa-specific genes among germline-related upregulated transcripts was lower than expected by chance for almost all species. Moreover, homologous genes related to proper DNA replication resulted the most common when comparing the considered species, while the regulation of transcription and post-transcriptional mechanisms appeared more variable, showing shared upregulated functions and domains, but very few homologous whole-length sequences.

CONCLUSIONS: Our wide-scale comparative analysis mostly confirmed previous molecular characterizations of specific germline-related lineages. Additionally, we observed a consistent signal throughout the whole data set, therefore comprehending both canonically defined germline samples (germ cells), and totipotent cell lineages classically considered somatic (neoblasts and archaeocytes). The phylostratigraphic analysis supported the less probable involvement of novel molecular factors in the germline-related transcriptional phenotype and highlighted the early origin of such cell programming and its conservation throughout evolution. Moreover, the fact that the mostly shared molecular factors were involved in DNA replication and repair suggests how fidelity in genetic material inheritance is a strong and conserved driver of germline-related molecular phenotype, while transcriptional and post-transcriptional regulations appear differently tuned among the lineages.}, } @article {pmid36717459, year = {2022}, author = {Pandey, T and Ma, DK}, title = {Stress-Induced Phenoptosis: Mechanistic Insights and Evolutionary Implications.}, journal = {Biochemistry. Biokhimiia}, volume = {87}, number = {12}, pages = {1504-1511}, doi = {10.1134/S0006297922120082}, pmid = {36717459}, issn = {1608-3040}, mesh = {Animals ; Humans ; *Caenorhabditis elegans/genetics ; *Apoptosis ; Aging/genetics ; Bacteria ; Signal Transduction ; Biological Evolution ; Mammals ; }, abstract = {Evolution by natural selection results in biological traits that enable organismic adaptation and survival under various stressful environments. External stresses can be sometimes too severe to overcome, leading to organismic death either because of failure in adapting to such stress, or alternatively, through a regulated form of organismic death (phenoptosis). While regulated cell deaths, including apoptosis, have been extensively studied, little is known about the molecular and cellular mechanisms underlying phenoptosis and its evolutionary significance for multicellular organisms. In this article, we review documented phenomena and mechanistic evidence emerging from studies of stress-induced phenoptosis in the multicellular organism C. elegans and stress-induced deaths at cellular levels in organisms ranging from bacteria to mammals, focusing on abiotic and pathogen stresses. Genes and signaling pathways involved in phenoptosis appear to promote organismic death during severe stress and aging, while conferring fitness and immune defense during mild stress and early life, consistent with their antagonistic pleiotropy actions. As cell apoptosis during development can shape tissues and organs, stress-induced phenoptosis may also contribute to possible benefits at the population level, through mechanisms including kin selection, abortive infection, and soma-to-germline resource allocation. Current models can generate experimentally testable predictions and conceptual frameworks with implications for understanding both stress-induced phenoptosis and natural aging.}, } @article {pmid36715204, year = {2023}, author = {Klure, DM and Greenhalgh, R and Parchman, TL and Matocq, MD and Galland, LM and Shapiro, MD and Dearing, MD}, title = {Hybridization in the absence of an ecotone favors hybrid success in woodrats (Neotoma spp.).}, journal = {Evolution; international journal of organic evolution}, volume = {77}, number = {4}, pages = {959-970}, pmid = {36715204}, issn = {1558-5646}, support = {T32 GM141848/GM/NIGMS NIH HHS/United States ; T32GM141848/NH/NIH HHS/United States ; }, mesh = {Humans ; Animals ; *Sigmodontinae/genetics ; *Hybridization, Genetic ; Nucleic Acid Hybridization ; }, abstract = {Hybridization is a common process that has broadly impacted the evolution of multicellular eukaryotes; however, how ecological factors influence this process remains poorly understood. Here, we report the findings of a 3-year recapture study of the Bryant's woodrat (Neotoma bryanti) and desert woodrat (Neotoma lepida), two species that hybridize within a creosote bush (Larrea tridentata) shrubland in Whitewater, CA, USA. We used a genotype-by-sequencing approach to characterize the ancestry distribution of individuals across this hybrid zone coupled with Cormack-Jolly-Seber modeling to describe demography. We identified a high frequency of hybridization at this site with ~40% of individuals possessing admixed ancestry, which is the result of multigenerational backcrossing and advanced hybrid-hybrid crossing. F1, F2, and advanced generation hybrids had apparent survival rates similar to parental N. bryanti, while parental and backcross N. lepida had lower apparent survival rates and were far less abundant. Compared to bimodal hybrid zones where hybrids are often rare and selected against, we find that hybrids at Whitewater are common and have comparable survival to the dominant parental species, N. bryanti. The frequency of hybridization at Whitewater is therefore likely limited by the abundance of the less common parental species, N. lepida, rather than selection against hybrids.}, } @article {pmid36711609, year = {2023}, author = {Shekhar, S and Guo, H and Colin, SP and Marshall, W and Kanso, E and Costello, JH}, title = {Cooperative hydrodynamics accompany multicellular-like colonial organization in the unicellular ciliate Stentor.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36711609}, support = {R35 GM130327/GM/NIGMS NIH HHS/United States ; }, abstract = {Evolution of multicellularity from early unicellular ancestors is arguably one of the most important transitions since the origin of life [1,2] . Multicellularity is often associated with higher nutrient uptake [3] , better defense against predation, cell specialization and better division of labor [4] . While many single-celled organisms exhibit both solitary and colonial existence [3,5,6] , the organizing principles governing the transition and the benefits endowed are less clear. Using the suspension-feeding unicellular protist Stentor coeruleus , we show that hydrodynamic coupling between proximal neighbors results in faster feeding flows that depend on the separation between individuals. Moreover, we find that the accrued benefits in feeding current enhancement are typically asymmetricâ€" individuals with slower solitary currents gain more from partnering than those with faster currents. We find that colony-formation is ephemeral in Stentor and individuals in colonies are highly dynamic unlike other colony-forming organisms like Volvox carteri [3] . Our results demonstrate benefits endowed by the colonial organization in a simple unicellular organism and can potentially provide fundamental insights into the selective forces favoring early evolution of multicellular organization.}, } @article {pmid36711513, year = {2023}, author = {Pineau, RM and Demory, D and Libby, E and Lac, DT and Day, TC and Bravo, P and Yunker, PJ and Weitz, JS and Bozdag, GO and Ratcliff, WC}, title = {Emergence and maintenance of stable coexistence during a long-term multicellular evolution experiment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.01.19.524803}, pmid = {36711513}, abstract = {The evolution of multicellular life spurred evolutionary radiations, fundamentally changing many of Earth’s ecosystems. Yet little is known about how early steps in the evolution of multicellularity transform eco-evolutionary dynamics, e.g., via niche expansion processes that may facilitate coexistence. Using long-term experimental evolution in the snowflake yeast model system, we show that the evolution of multicellularity drove niche partitioning and the adaptive divergence of two distinct, specialized lineages from a single multicellular ancestor. Over 715 daily transfers, snowflake yeast were subject to selection for rapid growth in rich media, followed by selection favoring larger group size. Both small and large cluster-forming lineages evolved from a monomorphic ancestor, coexisting for over ~4,300 generations. These small and large sized snowflake yeast lineages specialized on divergent aspects of a trade-off between growth rate and survival, mirroring predictions from ecological theory. Through modeling and experimentation, we demonstrate that coexistence is maintained by a trade-off between organismal size and competitiveness for dissolved oxygen. Taken together, this work shows how the evolution of a new level of biological individuality can rapidly drive adaptive diversification and the expansion of a nascent multicellular niche, one of the most historically-impactful emergent properties of this evolutionary transition.}, } @article {pmid36698752, year = {2023}, author = {Moriel, A and Wolfenson, H and Bouchbinder, E}, title = {Characteristic energy scales of active fluctuations in adherent cells.}, journal = {Biophysical reports}, volume = {3}, number = {1}, pages = {100099}, pmid = {36698752}, issn = {2667-0747}, abstract = {Cell-matrix and cell-cell adhesion play important roles in a wide variety of physiological processes, from the single-cell level to the large scale, multicellular organization of tissues. Cells actively apply forces to their environment, either extracellular matrix or neighboring cells, as well as sense its biophysical properties. The fluctuations associated with these active processes occur on an energy scale much larger than that of ordinary thermal equilibrium fluctuations, yet their statistical properties and characteristic scales are not fully understood. Here, we compare measurements of the energy scale of active cellular fluctuations-an effective cellular temperature-in four different biophysical settings, involving both single-cell and cell-aggregate experiments under various control conditions, different cell types, and various biophysical observables. The results indicate that a similar energy scale of active fluctuations might characterize the same cell type in different settings, though it may vary among different cell types, being approximately six to eight orders of magnitude larger than the ordinary thermal energy at room temperature. These findings call for extracting the energy scale of active fluctuations over a broader range of cell types, experimental settings, and biophysical observables and for understanding the biophysical origin and significance of such cellular energy scales.}, } @article {pmid36693985, year = {2023}, author = {Trivedi, DD and Dalai, SK and Bakshi, SR}, title = {The Mystery of Cancer Resistance: A Revelation Within Nature.}, journal = {Journal of molecular evolution}, volume = {91}, number = {2}, pages = {133-155}, pmid = {36693985}, issn = {1432-1432}, mesh = {Humans ; Horses ; Animals ; Mice ; *Carcinogens, Environmental ; *Neoplasms/genetics ; Immunity, Innate ; Mole Rats ; Mammals ; Tumor Microenvironment ; }, abstract = {Cancer, a disease due to uncontrolled cell proliferation is as ancient as multicellular organisms. A 255-million-years-old fossilized forerunner mammal gorgonopsian is probably the oldest evidence of cancer, to date. Cancer seems to have evolved by adapting to the microenvironment occupied by immune sentinel, modulating the cellular behavior from cytotoxic to regulatory, acquiring resistance to chemotherapy and surviving hypoxia. The interaction of genes with environmental carcinogens is central to cancer onset, seen as a spectrum of cancer susceptibility among human population. Cancer occurs in life forms other than human also, although their exposure to environmental carcinogens can be different. Role of genetic etiology in cancer in multiple species can be interesting with regard to not only cancer susceptibility, but also genetic conservation and adaptation in speciation. The widely used model organisms for cancer research are mouse and rat which are short-lived and reproduce rapidly. Research in these cancer prone animal models has been valuable as these have led to cancer therapy. However, another rewarding area of cancer research can be the cancer-resistant animal species. The Peto's paradox and G-value paradox are evident when natural cancer resistance is observed in large mammals, like elephant and whale, small rodents viz. Naked Mole Rat and Blind Mole Rat, and Bat. The cancer resistance remains to be explored in other small or large and long-living animals like giraffe, camel, rhinoceros, water buffalo, Indian bison, Shire horse, polar bear, manatee, elephant seal, walrus, hippopotamus, turtle and tortoise, sloth, and squirrel. Indeed, understanding the molecular mechanisms of avoiding neoplastic transformation across various life forms can be potentially having translational value for human cancer management. Adapted and Modified from (Hanahan and Weinberg 2011).}, } @article {pmid36692278, year = {2022}, author = {Forterre, P and Gaïa, M}, title = {[Viruses and the evolution of modern eukaryotic cells].}, journal = {Medecine sciences : M/S}, volume = {38}, number = {12}, pages = {990-998}, doi = {10.1051/medsci/2022164}, pmid = {36692278}, issn = {1958-5381}, mesh = {Humans ; *Eukaryotic Cells ; Phylogeny ; *Viruses/genetics ; Eukaryota/genetics ; Cell Nucleus ; Evolution, Molecular ; Biological Evolution ; }, abstract = {It is now well accepted that viruses have played an important role in the evolution of modern eukaryotes. In this review, we suggest that interactions between ancient eukaryoviruses and proto-eukaryotes also played a major role in eukaryogenesis. We discuss phylogenetic analyses that highlight the viral origin of several key proteins in the molecular biology of eukaryotes. We also discuss recent observations that, by analogy, could suggest a viral origin of the cellular nucleus. Finally, we hypothesize that mechanisms of cell differentiation in multicellular organisms might have originated from mechanisms implemented by viruses to transform infected cells into virocells.}, } @article {pmid36689549, year = {2023}, author = {Tuohinto, K and DiMaio, TA and Kiss, EA and Laakkonen, P and Saharinen, P and Karnezis, T and Lagunoff, M and Ojala, PM}, title = {KSHV infection of endothelial precursor cells with lymphatic characteristics as a novel model for translational Kaposi's sarcoma studies.}, journal = {PLoS pathogens}, volume = {19}, number = {1}, pages = {e1010753}, pmid = {36689549}, issn = {1553-7374}, support = {R01 CA189986/CA/NCI NIH HHS/United States ; R01 CA217788/CA/NCI NIH HHS/United States ; R21 CA240479/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Sarcoma, Kaposi ; *Herpesvirus 8, Human/genetics ; Endothelial Cells ; Endothelium, Vascular/pathology ; }, abstract = {Kaposi's sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), a hyperplasia consisting of enlarged malformed vasculature and spindle-shaped cells, the main proliferative component of KS. While spindle cells express markers of lymphatic and blood endothelium, the origin of spindle cells is unknown. Endothelial precursor cells have been proposed as the source of spindle cells. We previously identified two types of circulating endothelial colony forming cells (ECFCs), ones that expressed markers of blood endothelium and ones that expressed markers of lymphatic endothelium. Here we examined both blood and lymphatic ECFCs infected with KSHV. Lymphatic ECFCs are significantly more susceptible to KSHV infection than the blood ECFCs and maintain the viral episomes during passage in culture while the blood ECFCs lose the viral episome. Only the KSHV-infected lymphatic ECFCs (K-ECFCLY) grew to small multicellular colonies in soft agar whereas the infected blood ECFCs and all uninfected ECFCs failed to proliferate. The K-ECFCLYs express high levels of SOX18, which supported the maintenance of high copy number of KSHV genomes. When implanted subcutaneously into NSG mice, the K-ECFCLYs persisted in vivo and recapitulated the phenotype of KS tumor cells with high number of viral genome copies and spindling morphology. These spindle cell hallmarks were significantly reduced when mice were treated with SOX18 inhibitor, SM4. These data suggest that KSHV-infected lymphatic ECFCs can be utilized as a KSHV infection model for in vivo translational studies to test novel inhibitors representing potential treatment modalities for KS.}, } @article {pmid36688394, year = {2023}, author = {McShea, DW}, title = {Four reasons for scepticism about a human major transition in social individuality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1872}, pages = {20210403}, pmid = {36688394}, issn = {1471-2970}, mesh = {Animals ; Humans ; *Biological Evolution ; Eukaryota ; *Hominidae ; Selection, Genetic ; Reproduction ; }, abstract = {The 'major transitions in evolution' are mainly about the rise of hierarchy, new individuals arising at ever higher levels of nestedness, in particular the eukaryotic cell arising from prokaryotes, multicellular individuals from solitary protists and individuated societies from multicellular individuals. Some lists include human societies as a major transition, but based on a comparison with the non-human transitions, there are reasons for scepticism. (i) The foundation of the major transitions is hierarchy, but the cross-cutting interactions in human societies undermine hierarchical structure. (ii) Natural selection operates in three modes-stability, growth and reproductive success-and only the third produces the complex adaptations seen in fully individuated higher levels. But human societies probably evolve mainly in the stability and growth modes. (iii) Highly individuated entities are marked by division of labour and commitment to morphological differentiation, but in humans differentiation is mostly behavioural and mostly reversible. (iv) As higher-level individuals arise, selection drains complexity, drains parts, from lower-level individuals. But there is little evidence of a drain in humans. In sum, a comparison with the other transitions gives reasons to doubt that human social individuation has proceeded very far, or if it has, to doubt that it is a transition of the same sort. This article is part of the theme issue 'Human socio-cultural evolution in light of evolutionary transitions'.}, } @article {pmid36688393, year = {2023}, author = {Townsend, C and Ferraro, JV and Habecker, H and Flinn, MV}, title = {Human cooperation and evolutionary transitions in individuality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1872}, pages = {20210414}, pmid = {36688393}, issn = {1471-2970}, mesh = {Humans ; *Biological Evolution ; *Social Behavior ; Adaptation, Physiological ; Communication ; }, abstract = {A major evolutionary transition in individuality involves the formation of a cooperative group and the transformation of that group into an evolutionary entity. Human cooperation shares principles with those of multicellular organisms that have undergone transitions in individuality: division of labour, communication, and fitness interdependence. After the split from the last common ancestor of hominoids, early hominins adapted to an increasingly terrestrial niche for several million years. We posit that new challenges in this niche set in motion a positive feedback loop in selection pressure for cooperation that ratcheted coevolutionary changes in sociality, communication, brains, cognition, kin relations and technology, eventually resulting in egalitarian societies with suppressed competition and rapid cumulative culture. The increasing pace of information innovation and transmission became a key aspect of the evolutionary niche that enabled humans to become formidable cooperators with explosive population growth, the ability to cooperate and compete in groups of millions, and emergent social norms, e.g. private property. Despite considerable fitness interdependence, the rise of private property, in concert with population explosion and socioeconomic inequality, subverts potential transition of human groups into evolutionary entities due to resurgence of latent competition and conflict. This article is part of the theme issue 'Human socio-cultural evolution in light of evolutionary transitions'.}, } @article {pmid36688387, year = {2023}, author = {Davison, DR and Michod, RE}, title = {Steps to individuality in biology and culture.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1872}, pages = {20210407}, pmid = {36688387}, issn = {1471-2970}, mesh = {Animals ; Humans ; Biological Evolution ; *Hominidae ; *Cultural Evolution ; Biology ; }, abstract = {Did human culture arise through an evolutionary transition in individuality (ETI)? To address this question, we examine the steps of biological ETIs to see how they could apply to the evolution of human culture. For concreteness, we illustrate the ETI stages using a well-studied example, the evolution of multicellularity in the volvocine algae. We then consider how those stages could apply to a cultural transition involving integrated groups of cultural traditions and the hominins that create and transmit traditions. We focus primarily on the early Pleistocene and examine hominin carnivory and the cultural change from Oldowan to Acheulean technology. We use Pan behaviour as an outgroup comparison. We summarize the important similarities and differences we find between ETI stages in the biological and cultural realms. As we are not cultural anthropologists, we may overlook or be mistaken in the processes we associate with each step. We hope that by clearly describing these steps to individuality and illustrating them with cultural principles and processes, other researchers may build upon our initial exercise. Our analysis supports the hypothesis that human culture has undergone an ETI beginning with a Pan-like ancestor, continuing during the Pleistocene, and culminating in modern human culture. This article is part of the theme issue 'Human socio-cultural evolution in light of evolutionary transitions'.}, } @article {pmid36684435, year = {2022}, author = {Cofre, J and Saalfeld, K}, title = {The first embryo, the origin of cancer and animal phylogeny. I. A presentation of the neoplastic process and its connection with cell fusion and germline formation.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {1067248}, pmid = {36684435}, issn = {2296-634X}, abstract = {The decisive role of Embryology in understanding the evolution of animal forms is founded and deeply rooted in the history of science. It is recognized that the emergence of multicellularity would not have been possible without the formation of the first embryo. We speculate that biophysical phenomena and the surrounding environment of the Ediacaran ocean were instrumental in co-opting a neoplastic functional module (NFM) within the nucleus of the first zygote. Thus, the neoplastic process, understood here as a biological phenomenon with profound embryologic implications, served as the evolutionary engine that favored the formation of the first embryo and cancerous diseases and allowed to coherently create and recreate body shapes in different animal groups during evolution. In this article, we provide a deep reflection on the Physics of the first embryogenesis and its contribution to the exaptation of additional NFM components, such as the extracellular matrix. Knowledge of NFM components, structure, dynamics, and origin advances our understanding of the numerous possibilities and different innovations that embryos have undergone to create animal forms via Neoplasia during evolutionary radiation. The developmental pathways of Neoplasia have their origins in ctenophores and were consolidated in mammals and other apical groups.}, } @article {pmid36679107, year = {2023}, author = {Zhou, Y and Li, G and Han, G and Xun, L and Mao, S and Yang, L and Wang, Y}, title = {Developmental Programmed Cell Death Involved in Ontogenesis of Dictamnus dasycarpus Capitate Glandular Hairs.}, journal = {Plants (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {36679107}, issn = {2223-7747}, support = {31200152//National Natural Science Foundation of China/ ; 2020K-13//Science and Technology Program of Shaanxi Academy of Sciences/ ; 2022NY-142//Key Research and Development Program of Shaanxi/ ; 2022JM-110//Key Research and Development Program of Shaanxi/ ; }, abstract = {Plant glandular trichomes have received much attention due to their commercial and biological value. Recent studies have focused on the development of various glands in plants, suggesting that programmed cell death (PCD) may play an important role during the development of plant secretory structures. However, the development processes and cytological characteristics in different types of plant secretory structures differed significantly. This study aims to provide new data on the developmental PCD of the capitate glandular hairs in Dictamnus dasycarpus. Light, scanning, immunofluorescence labeling, and transmission electron microscopy were used to determine the different developmental processes of the capitate glandular hairs from a cytological perspective. Morphologically, the capitate glandular hair originates from one initial epidermal cell and differentiates into a multicellular trichome characterized by two basal cells, two lines of stalk cells, and a multicellular head. It is also histochemically detected by essential oils. TUNEL-positive reactions identified nuclei with diffused fluorescence or an irregular figure by DAPI, and Evans blue staining showed that the head and stalk cells lost their viability. Ultrastructural evidence revealed the developmental process by two possible modes of PCD. Non-autolytic PCD was characterized by buckling cell walls and degenerated nuclei, mitochondria, plastids, multivesicular body (MVB), and end-expanded endoplasmic reticulum in the condensed cytoplasm, which were mainly observed in the head cells. The MVB was detected in the degraded vacuole, a degraded nucleus with condensed chromatin and diffused membrane, and eventual loss of the vacuole membrane integrity exhibited typical evidence of vacuole-mediated autolytic PCD in the stalk cells. Furthermore, protoplasm degeneration coupled with dark oil droplets and numerous micro-dark osmiophilic substances was observed during late stages. The secretion mode of essential oils is also described in this paper.}, } @article {pmid36655713, year = {2023}, author = {Römling, U}, title = {Is biofilm formation intrinsic to the origin of life?.}, journal = {Environmental microbiology}, volume = {25}, number = {1}, pages = {26-39}, pmid = {36655713}, issn = {1462-2920}, mesh = {Humans ; *Biofilms ; }, abstract = {Biofilms are multicellular, often surface-associated, communities of autonomous cells. Their formation is the natural mode of growth of up to 80% of microorganisms living on this planet. Biofilms refractory towards antimicrobial agents and the actions of the immune system due to their tolerance against multiple environmental stresses. But how did biofilm formation arise? Here, I argue that the biofilm lifestyle has its foundation already in the fundamental, surface-triggered chemical reactions and energy preserving mechanisms that enabled the development of life on earth. Subsequently, prototypical biofilm formation has evolved and diversified concomitantly in composition, cell morphology and regulation with the expansion of prokaryotic organisms and their radiation by occupation of diverse ecological niches. This ancient origin of biofilm formation thus mirrors the harnessing environmental conditions that have been the rule rather than the exception in microbial life. The subsequent emergence of the association of microbes, including recent human pathogens, with higher organisms can be considered as the entry into a nutritional and largely stress-protecting heaven. Nevertheless, basic mechanisms of biofilm formation have surprisingly been conserved and refunctionalized to promote sustained survival in new environments.}, } @article {pmid36650459, year = {2023}, author = {Nozaki, H and Mori, F and Tanaka, Y and Matsuzaki, R and Yamashita, S and Yamaguchi, H and Kawachi, M}, title = {Cryopreservation of two species of the multicellular volvocine green algal genus Astrephomene.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {16}, pmid = {36650459}, issn = {1471-2180}, support = {G-2022-1-004//The Institute for Fermentation, Osaka (IFO)/ ; 20H03299//MEXT/ JSPS KAKENHI/ ; }, mesh = {*Chlorophyta/genetics ; Cryopreservation/methods ; Freezing ; Dimethylformamide ; }, abstract = {BACKGROUND: Astrephomene is an interesting green algal genus that, together with Volvox, shows convergent evolution of spheroidal multicellular bodies with somatic cells of the colonial or multicellular volvocine lineage. A recent whole-genome analysis of A. gubernaculifera resolved the molecular-genetic basis of such convergent evolution, and two species of Astrephomene were described. However, maintenance of culture strains of Astrephomene requires rapid inoculation of living cultures, and cryopreserved culture strains have not been established in public culture collections.

RESULTS: To establish cryopreserved culture strains of two species of Astrephomene, conditions for cryopreservation of the two species were investigated using immature and mature vegetative colonies and two cryoprotectants: N,N-dimethylformamide (DMF) and hydroxyacetone (HA). Rates of cell survival of the A. gubernaculifera or A. perforata strain after two-step cooling and freezing in liquid nitrogen were compared between different concentrations (3 and 6%) of DMF and HA and two types of colonies: immature colonies (small colonies newly released from the parent) and mature colonies (large colonies just before daughter colony formation). The highest rate of survival [11 ± 13% (0.36-33%) by the most probable number (MPN) method] of A. gubernaculifera strain NIES-4017 (established in 2014) was obtained when culture samples of immature colonies were subjected to cryogenic treatment with 6% DMF. In contrast, culture samples of mature colonies subjected to 3% HA cryogenic treatment showed the highest "MPN survival" [5.5 ± 5.9% (0.12-12%)] in A. perforata. Using the optimized cryopreservation conditions for each species, survival after freezing in liquid nitrogen was examined for six other strains of A. gubernaculifera (established from 1962 to 1981) and another A. perforata strain maintained in the Microbial Culture Collection at the National Institute for Environmental Studies (MCC-NIES). We obtained ≥0.1% MPN survival of the A. perforata strain. However, only two of the six strains of A. gubernaculifera showed ≥0.1% MPN survival. By using the optimal cryopreserved conditions obtained for each species, five cryopreserved strains of two species of Astrephomene were established and deposited in the MCC-NIES.

CONCLUSIONS: The optimal cryopreservation conditions differed between the two species of Astrephomene. Cryopreservation of long-term-maintained strains of A. gubernaculifera may be difficult; further studies of cryopreservation of these strains are needed.}, } @article {pmid36646908, year = {2023}, author = {Muñoz-Gómez, SA}, title = {Energetics and evolution of anaerobic microbial eukaryotes.}, journal = {Nature microbiology}, volume = {8}, number = {2}, pages = {197-203}, pmid = {36646908}, issn = {2058-5276}, mesh = {*Eukaryota ; Anaerobiosis ; *Mitochondria/metabolism ; Eukaryotic Cells/metabolism ; Fermentation ; }, abstract = {Mitochondria and aerobic respiration have been suggested to be required for the evolution of eukaryotic cell complexity. Aerobic respiration is several times more energetically efficient than fermentation. Moreover, aerobic respiration occurs at internalized mitochondrial membranes that are not constrained by a sublinear scaling with cell volume. However, diverse and complex anaerobic eukaryotes (for example, free-living and parasitic unicellular, and even small multicellular, eukaryotes) that exclusively rely on fermentation for energy generation have evolved repeatedly from aerobic ancestors. How do fermenting eukaryotes maintain their cell volumes and complexity while relying on such a low energy-yielding process? Here I propose that reduced rates of ATP generation in fermenting versus respiring eukaryotes are compensated for by longer cell cycles that satisfy lifetime energy demands. A literature survey and growth efficiency calculations show that fermenting eukaryotes divide approximately four to six times slower than aerobically respiring counterparts with similar cell volumes. Although ecological advantages such as competition avoidance offset lower growth rates and yields in the short term, fermenting eukaryotes inevitably have fewer physiological and ecological possibilities, which ultimately constrain their long-term evolutionary trajectories.}, } @article {pmid36641836, year = {2023}, author = {Barrenechea Angeles, I and Romero-Martínez, ML and Cavaliere, M and Varrella, S and Francescangeli, F and Piredda, R and Mazzocchi, MG and Montresor, M and Schirone, A and Delbono, I and Margiotta, F and Corinaldesi, C and Chiavarini, S and Montereali, MR and Rimauro, J and Parrella, L and Musco, L and Dell'Anno, A and Tangherlini, M and Pawlowski, J and Frontalini, F}, title = {Encapsulated in sediments: eDNA deciphers the ecosystem history of one of the most polluted European marine sites.}, journal = {Environment international}, volume = {172}, number = {}, pages = {107738}, doi = {10.1016/j.envint.2023.107738}, pmid = {36641836}, issn = {1873-6750}, mesh = {Humans ; Animals ; *Ecosystem ; *Biodiversity ; Biota ; Europe ; Human Activities ; Geologic Sediments ; }, abstract = {The Anthropocene is characterized by dramatic ecosystem changes driven by human activities. The impact of these activities can be assessed by different geochemical and paleontological proxies. However, each of these proxies provides only a fragmentary insight into the effects of anthropogenic impacts. It is highly challenging to reconstruct, with a holistic view, the state of the ecosystems from the preindustrial period to the present day, covering all biological components, from prokaryotes to multicellular eukaryotes. Here, we used sedimentary ancient DNA (sedaDNA) archives encompassing all trophic levels of biodiversity to reconstruct the two century-natural history in Bagnoli-Coroglio (Gulf of Pozzuoli, Tyrrhenian Sea), one of the most polluted marine-coastal sites in Europe. The site was characterized by seagrass meadows and high eukaryotic diversity until the beginning of the 20th century. Then, the ecosystem completely changed, with seagrasses and associated fauna as well as diverse groups of planktonic and benthic protists being replaced by low diversity biota dominated by dinophyceans and infaunal metazoan species. The sedaDNA analysis revealed a five-phase evolution of the area, where changes appear as the result of a multi-level cascade effect of impacts associated with industrial activities, urbanization, water circulation and land-use changes. The sedaDNA allowed to infer reference conditions that must be considered when restoration actions are to be implemented.}, } @article {pmid36637886, year = {2023}, author = {Kuzdzal-Fick, JJ and Moreno, A and Broersma, CME and Cooper, TF and Ostrowski, EA}, title = {From individual behaviors to collective outcomes: fruiting body formation in Dictyostelium as a group-level phenotype.}, journal = {Evolution; international journal of organic evolution}, volume = {77}, number = {3}, pages = {731-745}, doi = {10.1093/evolut/qpac038}, pmid = {36637886}, issn = {1558-5646}, mesh = {*Dictyostelium/genetics ; Phenotype ; Genotype ; Reproduction ; }, abstract = {Collective phenotypes, which arise from the interactions among individuals, can be important for the evolution of higher levels of biological organization. However, how a group's composition determines its collective phenotype remains poorly understood. When starved, cells of the social amoeba Dictyostelium discoideum cooperate to build a multicellular fruiting body, and the morphology of the fruiting body is likely advantageous to the surviving spores. We assessed how the number of strains, as well as their genetic and geographic relationships to one another, impact the group's morphology and productivity. We find that some strains consistently enhance or detract from the productivity of their groups, regardless of the identity of the other group members. We also detect extensive pairwise and higher-order genotype interactions, which collectively have a large influence on the group phenotype. Whereas previous work in Dictyostelium has focused almost exclusively on whether spore production is equitable when strains cooperate to form multicellular fruiting bodies, our results suggest a previously unrecognized impact of chimeric co-development on the group phenotype. Our results demonstrate how interactions among members of a group influence collective phenotypes and how group phenotypes might in turn impact selection on the individual.}, } @article {pmid36637107, year = {2023}, author = {Iyer, J and Pillai, S and Munguia-Lopez, JG and Zhang, Y and Mielkozorova, M and Tran, SD}, title = {Salivary gland bioengineering - yesterday, today, tomorrow!.}, journal = {Histology and histopathology}, volume = {38}, number = {6}, pages = {607-621}, pmid = {36637107}, issn = {1699-5848}, support = {FBD-181455//CIHR fund/ ; }, mesh = {Humans ; *Quality of Life ; Salivary Glands/physiology ; *Xerostomia/diagnosis/therapy ; Salivation ; Bioengineering ; }, abstract = {Salivary glands are specialized structures developed as an extensively compact, arborized design through classical embryogenesis, accompanied by a cascade of events channelized by numerous growth factors and genetic regulatory pathways. Salivary secretions maintain oral homeostasis and, when diminished in certain conditions, present as xerostomia or salivary hypofunction, adversely impacting the patient's quality of life. The current available treatments primarily aim at tackling the immediate symptoms providing temporary relief to the patient. Despite scientific efforts to develop permanent and effective solutions to restore salivation, a significant permanent treatment is yet to be established. Tissue engineering has proven as a promising remedial tool in several diseases, as well as in xerostomia, and aims to restore partial loss of organ function. Recapitulating the physiological cellular microenvironment to in vitro culture conditions is constantly evolving. Replicating the dynamic multicellular interactions, genetic pathways, and cytomorphogenic forces, as displayed during salivary gland development have experienced considerable barriers. Through this review, we endeavour to provide an outlook on the evolution of in vitro salivary gland research, highlighting the key bioengineering advances and the challenges faced with the current therapeutic strategies for salivary hypofunction, with an insight into our team's scientific contributions.}, } @article {pmid36636779, year = {2023}, author = {Gombos, S and Miras, M and Howe, V and Xi, L and Pottier, M and Kazemein Jasemi, NS and Schladt, M and Ejike, JO and Neumann, U and Hänsch, S and Kuttig, F and Zhang, Z and Dickmanns, M and Xu, P and Stefan, T and Baumeister, W and Frommer, WB and Simon, R and Schulze, WX}, title = {A high-confidence Physcomitrium patens plasmodesmata proteome by iterative scoring and validation reveals diversification of cell wall proteins during evolution.}, journal = {The New phytologist}, volume = {238}, number = {2}, pages = {637-653}, doi = {10.1111/nph.18730}, pmid = {36636779}, issn = {1469-8137}, support = {951292/ERC_/European Research Council/International ; 101023589/MCCC_/Marie Curie/United Kingdom ; 101023981/MCCC_/Marie Curie/United Kingdom ; }, mesh = {*Proteome/metabolism ; *Plasmodesmata/metabolism ; Phylogeny ; Reproducibility of Results ; Cell Wall/metabolism ; }, abstract = {Plasmodesmata (PD) facilitate movement of molecules between plant cells. Regulation of this movement is still not understood. Plasmodesmata are hard to study, being deeply embedded within cell walls and incorporating several membrane types. Thus, structure and protein composition of PD remain enigmatic. Previous studies of PD protein composition identified protein lists with few validations, making functional conclusions difficult. We developed a PD scoring approach in iteration with large-scale systematic localization, defining a high-confidence PD proteome of Physcomitrium patens (HC300). HC300, together with bona fide PD proteins from literature, were placed in Pddb. About 65% of proteins in HC300 were not previously PD-localized. Callose-degrading glycolyl hydrolase family 17 (GHL17) is an abundant protein family with representatives across evolutionary scale. Among GHL17s, we exclusively found members of one phylogenetic clade with PD localization and orthologs occur only in species with developed PD. Phylogenetic comparison was expanded to xyloglucan endotransglucosylases/hydrolases and Exordium-like proteins, which also diversified into PD-localized and non-PD-localized members on distinct phylogenetic clades. Our high-confidence PD proteome HC300 provides insights into diversification of large protein families. Iterative and systematic large-scale localization across plant species strengthens the reliability of HC300 as basis for exploring structure, function, and evolution of this important organelle.}, } @article {pmid36616337, year = {2023}, author = {Wu, X and Liu, X and Zhang, S and Zhou, Y}, title = {Cell Division and Meristem Dynamics in Fern Gametophytes.}, journal = {Plants (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {36616337}, issn = {2223-7747}, support = {IOS 1931114//National Science Foundation/ ; }, abstract = {One of the most important questions in all multicellular organisms is how to define and maintain different cell fates during continuous cell division and proliferation. Plant meristems provide a unique research system to address this fundamental question because meristems dynamically maintain themselves and sustain organogenesis through balancing cell division and cell differentiation. Different from the gametophytes of seed plants that depend on their sporophytes and lack meristems, the gametophytes of seed-free ferns develop different types of meristems (including apical cell-based meristems and multicellular apical and marginal meristems) to promote independent growth and proliferation during the sexual gametophyte phase. Recent studies combining confocal time-lapse imaging and computational image analysis reveal the cellular basis of the initiation and proliferation of different types of meristems in fern gametophytes, providing new insights into the evolution of meristems in land plants. In this review, we summarize the recent progress in understanding the cell growth dynamics in fern gametophytes and discuss both conserved and diversified mechanisms underlying meristem cell proliferation in seed-free vascular plants.}, } @article {pmid36611928, year = {2022}, author = {von der Heyde, B and Hallmann, A}, title = {Cell Type-Specific Pherophorins of Volvox carteri Reveal Interplay of Both Cell Types in ECM Biosynthesis.}, journal = {Cells}, volume = {12}, number = {1}, pages = {}, pmid = {36611928}, issn = {2073-4409}, mesh = {*Volvox/genetics/metabolism ; Phylogeny ; Extracellular Matrix/metabolism ; *Chlorophyta/genetics ; Extracellular Matrix Proteins/metabolism ; }, abstract = {The spheroidal green algae Volvox carteri serves as a model system to investigate the formation of a complex, multifunctional extracellular matrix (ECM) in a relatively simple, multicellular organism with cell differentiation. The V. carteri ECM is mainly composed of hydroxyproline-rich glycoproteins (HRGPs) and there are diverse region-specific, anatomically distinct structures in the ECM. One large protein family with importance for ECM biosynthesis stands out: the pherophorins. The few pherophorins previously extracted from the ECM and characterized, were specifically expressed by somatic cells. However, the localization and function of most pherophorins is unknown. Here, we provide a phylogenetic analysis of 153 pherophorins of V. carteri and its unicellular relative Chlamydomonas reinhardtii. Our analysis of cell type-specific mRNA expression of pherophorins in V. carteri revealed that, contrary to previous assumptions, only about half (52%) of the 102 investigated pherophorin-related genes show stronger expression in somatic cells, whereas about one-third (34%) of the genes show significant higher expression in reproductive cells (gonidia). We fused two pherophorin genes that are expressed by different cell types to yfp, stably expressed them in Volvox and studied the tagged proteins by live-cell imaging. In contrast to earlier biochemical approaches, this genetic approach also allows the in vivo analysis of non-extractable, covalently cross-linked ECM proteins. We demonstrate that the soma-specific pherophorin SSG185 is localized in the outermost ECM structures of the spheroid, the boundary zone and at the flagellar hillocks. SSG185:YFP is detectable as early as 1.5 h after completion of embryogenesis. It is then present for the rest of the life cycle. The gonidia-specific pherophorin PhG is localized in the gonidial cellular zone 1 ("gonidial vesicle") suggesting its involvement in the protection of gonidia and developing embryos until hatching. Even if somatic cells produce the main portion of the ECM of the spheroids, ECM components produced by gonidia are also required to cooperatively assemble the total ECM. Our results provide insights into the evolution of the pherophorin protein family and convey a more detailed picture of Volvox ECM synthesis.}, } @article {pmid36598979, year = {2023}, author = {Chuai, M and Serrano Nájera, G and Serra, M and Mahadevan, L and Weijer, CJ}, title = {Reconstruction of distinct vertebrate gastrulation modes via modulation of key cell behaviors in the chick embryo.}, journal = {Science advances}, volume = {9}, number = {1}, pages = {eabn5429}, pmid = {36598979}, issn = {2375-2548}, abstract = {The morphology of gastrulation driving the internalization of the mesoderm and endoderm differs markedly among vertebrate species. It ranges from involution of epithelial sheets of cells through a circular blastopore in amphibians to ingression of mesenchymal cells through a primitive streak in amniotes. By targeting signaling pathways controlling critical cell behaviors in the chick embryo, we generated crescent- and ring-shaped mesendoderm territories in which cells can or cannot ingress. These alterations subvert the formation of the chick primitive streak into the gastrulation modes seen in amphibians, reptiles, and teleost fish. Our experimental manipulations are supported by a theoretical framework linking cellular behaviors to self-organized multicellular flows outlined in detail in the accompanying paper. Together, this suggests that the evolution of gastrulation movements is largely determined by changes in a few critical cell behaviors in the mesendoderm territory across different species and controlled by a relatively small number of signaling pathways.}, } @article {pmid36598184, year = {2023}, author = {Dang, CC and Vinh, LS}, title = {Estimating amino acid substitution models for metazoan evolutionary studies.}, journal = {Journal of evolutionary biology}, volume = {36}, number = {3}, pages = {499-506}, doi = {10.1111/jeb.14147}, pmid = {36598184}, issn = {1420-9101}, mesh = {Animals ; Phylogeny ; *Evolution, Molecular ; Amino Acid Substitution ; Bayes Theorem ; *Proteins ; Models, Genetic ; }, abstract = {Amino acid substitution models represent the substitution rates among amino acids during the evolution of protein sequences. The models are a prerequisite for maximum likelihood or Bayesian methods to analyse the phylogenetic relationships among species based on their protein sequences. Estimating amino acid substitution models requires large protein datasets and intensive computation. In this paper, we presented the estimation of both time-reversible model (Q.met) and time non-reversible model (NQ.met) for multicellular animals (Metazoa). Analyses showed that the Q.met and NQ.met models were significantly better than existing models in analysing metazoan protein sequences. Moreover, the time non-reversible model NQ.met enables us to reconstruct the rooted phylogenetic tree for Metazoa. We recommend researchers to employ the Q.met and NQ.met models in analysing metazoan protein sequences.}, } @article {pmid36587372, year = {2023}, author = {Palmiero, M and Cantarosso, I and di Blasio, L and Monica, V and Peracino, B and Primo, L and Puliafito, A}, title = {Collective directional migration drives the formation of heteroclonal cancer cell clusters.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.13369}, pmid = {36587372}, issn = {1878-0261}, support = {IG 23211//Associazione Italiana per la Ricerca sul Cancro/ ; MFAG 25040//Associazione Italiana per la Ricerca sul Cancro/ ; //Fondazione Piemontese per la Ricerca sul Cancro/ ; //Fondazione Umberto Veronesi/ ; //Italian Ministry of Health/ ; 2019 PULA_RILO_19_01//Università degli Studi di Torino/ ; }, abstract = {Metastasisation occurs through the acquisition of invasive and survival capabilities that allow tumour cells to colonise distant sites. While the role of multicellular aggregates in cancer dissemination is acknowledged, the mechanisms that drive the formation of multiclonal cell aggregates are not fully elucidated. Here, we show that cancer cells of different tissue of origins can perform collective directional migration and can actively form heteroclonal aggregates in 3D, through a proliferation-independent mechanism. Coalescence of distant cell clusters is mediated by subcellular actin-rich protrusions and multicellular outgrowths that extend towards neighbouring aggregates. Coherently, perturbation of cytoskeletal dynamics impairs collective migration while myosin II activation is necessary for multicellular movements. We put forward the hypothesis that cluster attraction is mediated by secreted soluble factors. Such a hypothesis is consistent with the abrogation of aggregation by inhibition of PI3K/AKT/mTOR and MEK/ERK, the chemoattracting activity of conditioned culture media and with a wide screening of secreted proteins. Our results present a novel collective migration model and shed light on the mechanisms of formation of heteroclonal aggregates in cancer.}, } @article {pmid36585440, year = {2022}, author = {Lynch, M and Trickovic, B and Kempes, CP}, title = {Evolutionary scaling of maximum growth rate with organism size.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {22586}, pmid = {36585440}, issn = {2045-2322}, support = {R35 GM122566/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; *Genetic Drift ; Eukaryota/genetics ; Mutation ; Selection, Genetic ; }, abstract = {Data from nearly 1000 species reveal the upper bound to rates of biomass production achievable by natural selection across the Tree of Life. For heterotrophs, maximum growth rates scale positively with organism size in bacteria but negatively in eukaryotes, whereas for phototrophs, the scaling is negligible for cyanobacteria and weakly negative for eukaryotes. These results have significant implications for understanding the bioenergetic consequences of the transition from prokaryotes to eukaryotes, and of the expansion of some groups of the latter into multicellularity. The magnitudes of the scaling coefficients for eukaryotes are significantly lower than expected under any proposed physical-constraint model. Supported by genomic, bioenergetic, and population-genetic data and theory, an alternative hypothesis for the observed negative scaling in eukaryotes postulates that growth-diminishing mutations with small effects passively accumulate with increasing organism size as a consequence of associated increases in the power of random genetic drift. In contrast, conditional on the structural and functional features of ribosomes, natural selection has been able to promote bacteria with the fastest possible growth rates, implying minimal conflicts with both bioenergetic constraints and random genetic drift. If this extension of the drift-barrier hypothesis is correct, the interpretations of comparative studies of biological traits that have traditionally ignored differences in population-genetic environments will require revisiting.}, } @article {pmid36553613, year = {2022}, author = {Kozlov, AP}, title = {The Theory of Carcino-Evo-Devo and Its Non-Trivial Predictions.}, journal = {Genes}, volume = {13}, number = {12}, pages = {}, pmid = {36553613}, issn = {2073-4425}, mesh = {Animals ; Humans ; *Genes, Tumor Suppressor ; Oncogenes ; Cell Differentiation ; *Neoplasms/genetics ; Fishes ; }, abstract = {To explain the sources of additional cell masses in the evolution of multicellular organisms, the theory of carcino-evo-devo, or evolution by tumor neofunctionalization, has been developed. The important demand for a new theory in experimental science is the capability to formulate non-trivial predictions which can be experimentally confirmed. Several non-trivial predictions were formulated using carcino-evo-devo theory, four of which are discussed in the present paper: (1) The number of cellular oncogenes should correspond to the number of cell types in the organism. The evolution of oncogenes, tumor suppressor and differentiation gene classes should proceed concurrently. (2) Evolutionarily new and evolving genes should be specifically expressed in tumors (TSEEN genes). (3) Human orthologs of fish TSEEN genes should acquire progressive functions connected with new cell types, tissues and organs. (4) Selection of tumors for new functions in the organism is possible. Evolutionarily novel organs should recapitulate tumor features in their development. As shown in this paper, these predictions have been confirmed by the laboratory of the author. Thus, we have shown that carcino-evo-devo theory has predictive power, fulfilling a fundamental requirement for a new theory.}, } @article {pmid36550365, year = {2022}, author = {Bowman, JL}, title = {The origin of a land flora.}, journal = {Nature plants}, volume = {8}, number = {12}, pages = {1352-1369}, pmid = {36550365}, issn = {2055-0278}, mesh = {*Biological Evolution ; Phylogeny ; Plants/genetics ; *Embryophyta/genetics ; }, abstract = {The origin of a land flora fundamentally shifted the course of evolution of life on earth, facilitating terrestrialization of other eukaryotic lineages and altering the planet's geology, from changing atmospheric and hydrological cycles to transforming continental erosion processes. Despite algal lineages inhabiting the terrestrial environment for a considerable preceding period, they failed to evolve complex multicellularity necessary to conquer the land. About 470 million years ago, one lineage of charophycean alga evolved complex multicellularity via developmental innovations in both haploid and diploid generations and became land plants (embryophytes), which rapidly diversified to dominate most terrestrial habitats. Genome sequences have provided unprecedented insights into the genetic and genomic bases for embryophyte origins, with some embryophyte-specific genes being associated with the evolution of key developmental or physiological attributes, such as meristems, rhizoids and the ability to form mycorrhizal associations. However, based on the fossil record, the evolution of the defining feature of embryophytes, the embryo, and consequently the sporangium that provided a reproductive advantage, may have been most critical in their rise to dominance. The long timeframe and singularity of a land flora were perhaps due to the stepwise assembly of a large constellation of genetic innovations required to conquer the terrestrial environment.}, } @article {pmid36547392, year = {2022}, author = {Baselga-Cervera, B and Gettle, N and Travisano, M}, title = {Loss-of-heterozygosity facilitates a fitness valley crossing in experimentally evolved multicellular yeast.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1976}, pages = {20212722}, pmid = {36547392}, issn = {1471-2954}, mesh = {*Adaptation, Physiological/genetics ; *Biological Evolution ; Genotype ; Heterozygote ; *Saccharomyces cerevisiae/genetics ; *Loss of Heterozygosity ; *Genetic Fitness ; }, abstract = {Determining how adaptive possibilities do or do not become evolutionary realities is central to understanding the tempo and mode of evolutionary change. Some of the simplest evolutionary landscapes arise from underdominance at a single locus where the fitness valley consists of only one less-fit genotype. Despite their potential for rapid evolutionary change, few such examples have been investigated. We capitalized on an experimental system in which a significant evolutionary shift, the transition from uni-to-multicellularity, was observed in asexual diploid populations of Saccharomyces cerevisiae experimentally selected for increased settling rates. The multicellular phenotype results from recessive single-locus mutations that undergo loss-of-heterozygosity (LOH) events. By reconstructing the necessary heterozygous intermediate steps, we found that the evolution of multicellularity involves a decrease in size during the first steps. Heterozygous genotypes are 20% smaller in size than genotypes with functional alleles. Nevertheless, populations of heterozygotes give rise to multicellular genotypes more readily than unicellular genotypes with two functional alleles, by rapid LOH events. LOH drives adaptation that may enable rapid evolution in diploid yeast. Together these results show discordance between the phenotypic and genotypic multicellular transition. The evolutionary path to multicellularity, and the adaptive benefits of increased size, requires initial size reductions.}, } @article {pmid36546265, year = {2022}, author = {Liu, J and Zhang, W and He, K and Liu, L and Wang, C and Jiang, Y and Ma, S and Tian, J and Li, Y and Zhang, T and Tian, L and He, F and Paterson, GA and Wei, Y and Pan, Y and Lin, W}, title = {Survival of the magnetotactic bacterium Magnetospirillum gryphiswaldense exposed to Earth's lower near space.}, journal = {Science bulletin}, volume = {67}, number = {13}, pages = {1335-1339}, doi = {10.1016/j.scib.2022.03.005}, pmid = {36546265}, issn = {2095-9281}, mesh = {*Magnetospirillum ; Bacteria, Aerobic ; Gram-Negative Bacteria ; }, } @article {pmid36542495, year = {2023}, author = {Martinez, P and Ustyantsev, K and Biryukov, M and Mouton, S and Glasenburg, L and Sprecher, SG and Bailly, X and Berezikov, E}, title = {Genome assembly of the acoel flatworm Symsagittifera roscoffensis, a model for research on body plan evolution and photosymbiosis.}, journal = {G3 (Bethesda, Md.)}, volume = {13}, number = {2}, pages = {}, pmid = {36542495}, issn = {2160-1836}, mesh = {Animals ; *Platyhelminths/genetics ; Phylogeny ; Base Sequence ; Genome Size ; Transcriptome ; Chromosomes ; }, abstract = {Symsagittifera roscoffensis is a well-known member of the order Acoela that lives in symbiosis with the algae Tetraselmis convolutae during its adult stage. Its natural habitat is the eastern coast of the Atlantic, where at specific locations thousands of individuals can be found, mostly, lying in large pools on the surface of sand at low tide. As a member of the Acoela it has been thought as a proxy for ancestral bilaterian animals; however, its phylogenetic position remains still debated. In order to understand the basic structural characteristics of the acoel genome, we sequenced and assembled the genome of aposymbiotic species S. roscoffensis. The size of this genome was measured to be in the range of 910-940 Mb. Sequencing of the genome was performed using PacBio Hi-Fi technology. Hi-C and RNA-seq data were also generated to scaffold and annotate it. The resulting assembly is 1.1 Gb large (covering 118% of the estimated genome size) and highly continuous, with N50 scaffold size of 1.04 Mb. The repetitive fraction of the genome is 61%, of which 85% (half of the genome) are LTR retrotransposons. Genome-guided transcriptome assembly identified 34,493 genes, of which 29,351 are protein coding (BUSCO score 97.6%), and 30.2% of genes are spliced leader trans-spliced. The completeness of this genome suggests that it can be used extensively to characterize gene families and conduct accurate phylogenomic reconstructions.}, } @article {pmid36542491, year = {2023}, author = {Bonardd, S and Nandi, M and Hernández García, JI and Maiti, B and Abramov, A and Díaz Díaz, D}, title = {Self-Healing Polymeric Soft Actuators.}, journal = {Chemical reviews}, volume = {123}, number = {2}, pages = {736-810}, pmid = {36542491}, issn = {1520-6890}, mesh = {*Polymers/chemistry ; *Hydrogels/chemistry ; Temperature ; }, abstract = {Natural evolution has provided multicellular organisms with sophisticated functionalities and repair mechanisms for surviving and preserve their functions after an injury and/or infection. In this context, biological systems have inspired material scientists over decades to design and fabricate both self-healing polymeric materials and soft actuators with remarkable performance. The latter are capable of modifying their shape in response to environmental changes, such as temperature, pH, light, electrical/magnetic field, chemical additives, etc. In this review, we focus on the fusion of both types of materials, affording new systems with the potential to revolutionize almost every aspect of our modern life, from healthcare to environmental remediation and energy. The integration of stimuli-triggered self-healing properties into polymeric soft actuators endow environmental friendliness, cost-saving, enhanced safety, and lifespan of functional materials. We discuss the details of the most remarkable examples of self-healing soft actuators that display a macroscopic movement under specific stimuli. The discussion includes key experimental data, potential limitations, and mechanistic insights. Finally, we include a general table providing at first glance information about the nature of the external stimuli, conditions for self-healing and actuation, key information about the driving forces behind both phenomena, and the most important features of the achieved movement.}, } @article {pmid36541176, year = {2022}, author = {La Fortezza, M and Velicer, GJ}, title = {Correction to: 'Social selection within aggregative multicellular development drives morphological evolution' (2021) by La Fortezza and Velicer.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1989}, pages = {20222290}, doi = {10.1098/rspb.2022.2290}, pmid = {36541176}, issn = {1471-2954}, } @article {pmid36539037, year = {2023}, author = {Rangarajan, ES and Smith, EW and Izard, T}, title = {The nematode α-catenin ortholog, HMP1, has an extended α-helix when bound to actin filaments.}, journal = {The Journal of biological chemistry}, volume = {299}, number = {2}, pages = {102817}, pmid = {36539037}, issn = {1083-351X}, mesh = {Animals ; *Actin Cytoskeleton/chemistry/metabolism/ultrastructure ; Actins/chemistry/metabolism/ultrastructure ; *alpha Catenin/chemistry/metabolism ; Cadherins/metabolism ; *Caenorhabditis elegans ; Mammals ; Protein Conformation, alpha-Helical ; Protein Domains ; Cryoelectron Microscopy ; Cell Adhesion ; Cell Communication ; }, abstract = {The regulation of cell-cell junctions during epidermal morphogenesis ensures tissue integrity, a process regulated by α-catenin. This cytoskeletal protein connects the cadherin complex to filamentous actin at cell-cell junctions. The cadherin-catenin complex plays key roles in cell physiology, organism development, and disease. While mutagenesis of Caenorhabditis elegans cadherin and catenin shows that these proteins are key for embryonic morphogenesis, we know surprisingly little about their structure and attachment to the cytoskeleton. In contrast to mammalian α-catenin that functions as a dimer or monomer, the α-catenin ortholog from C. elegans, HMP1 for humpback, is a monomer. Our cryogenic electron microscopy (cryoEM) structure of HMP1/α-catenin reveals that the amino- and carboxy-terminal domains of HMP1/α-catenin are disordered and not in contact with the remaining HMP1/α-catenin middle domain. Since the carboxy-terminal HMP1/α-catenin domain is the F-actin-binding domain (FABD), this interdomain constellation suggests that HMP1/α-catenin is constitutively active, which we confirm biochemically. Our perhaps most surprising finding, given the high sequence similarity between the mammalian and nematode proteins, is our cryoEM structure of HMP1/α-catenin bound to F-actin. Unlike the structure of mammalian α-catenin bound to F-actin, binding to F-actin seems to allosterically convert a loop region of the HMP1/α-catenin FABD to extend an HMP1/α-catenin FABD α-helix. We use cryoEM and bundling assays to show for the first time how the FABD of HMP1/α-catenin bundles actin in the absence of force. Collectively, our data advance our understanding of α-catenin regulation of cell-cell contacts and additionally aid our understanding of the evolution of multicellularity in metazoans.}, } @article {pmid36534348, year = {2022}, author = {Nery, MF and Rennó, M and Picorelli, A and Ramos, E}, title = {A phylogenetic review of cancer resistance highlights evolutionary solutions to Peto's Paradox.}, journal = {Genetics and molecular biology}, volume = {45}, number = {3 Suppl 1}, pages = {e20220133}, pmid = {36534348}, issn = {1415-4757}, abstract = {Cancer is a genetic disease present in all complex multicellular lineages. Finding ways to eliminate it is a goal of a large part of the scientific community and nature itself. Early, scientists realized that the cancer incidence at the species level was not related to the number of cells or lifespan, a phenomenon called Peto's Paradox. The interest in resolving this paradox triggered a growing interest in investigating the natural strategies for cancer suppression hidden in the animal's genomes. Here, we gathered information on the main mechanisms that confer resistance to cancer, currently described for lineages that have representatives with extended longevity and large body sizes. Some mechanisms to reduce or evade cancer are common and shared between lineages, while others are species-specific. The diversity of paths that evolution followed to face the cancer challenge involving coding, regulatory, and structural aspects of genomes is astonishing and much yet lacks discovery. Multidisciplinary studies involving oncology, ecology, and evolutionary biology and focusing on nonmodel species can greatly expand the frontiers of knowledge about cancer resistance in animals and may guide new promising treatments and prevention that might apply to humans.}, } @article {pmid36531949, year = {2022}, author = {Nguyen, NM and Merle, T and Broders-Bondon, F and Brunet, AC and Battistella, A and Land, EBL and Sarron, F and Jha, A and Gennisson, JL and Röttinger, E and Fernández-Sánchez, ME and Farge, E}, title = {Mechano-biochemical marine stimulation of inversion, gastrulation, and endomesoderm specification in multicellular Eukaryota.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {992371}, pmid = {36531949}, issn = {2296-634X}, abstract = {The evolutionary emergence of the primitive gut in Metazoa is one of the decisive events that conditioned the major evolutionary transition, leading to the origin of animal development. It is thought to have been induced by the specification of the endomesoderm (EM) into the multicellular tissue and its invagination (i.e., gastrulation). However, the biochemical signals underlying the evolutionary emergence of EM specification and gastrulation remain unknown. Herein, we find that hydrodynamic mechanical strains, reminiscent of soft marine flow, trigger active tissue invagination/gastrulation or curvature reversal via a Myo-II-dependent mechanotransductive process in both the metazoan Nematostella vectensis (cnidaria) and the multicellular choanoflagellate Choanoeca flexa. In the latter, our data suggest that the curvature reversal is associated with a sensory-behavioral feeding response. Additionally, like in bilaterian animals, gastrulation in the cnidarian Nematostella vectensis is shown to participate in the biochemical specification of the EM through mechanical activation of the β-catenin pathway via the phosphorylation of Y654-βcatenin. Choanoflagellates are considered the closest living relative to metazoans, and the common ancestor of choanoflagellates and metazoans dates back at least 700 million years. Therefore, the present findings using these evolutionarily distant species suggest that the primitive emergence of the gut in Metazoa may have been initiated in response to marine mechanical stress already in multicellular pre-Metazoa. Then, the evolutionary transition may have been achieved by specifying the EM via a mechanosensitive Y654-βcatenin dependent mechanism, which appeared during early Metazoa evolution and is specifically conserved in all animals.}, } @article {pmid36531944, year = {2022}, author = {Fisher, LAB and Schöck, F}, title = {The unexpected versatility of ALP/Enigma family proteins.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {963608}, pmid = {36531944}, issn = {2296-634X}, abstract = {One of the most intriguing features of multicellular animals is their ability to move. On a cellular level, this is accomplished by the rearrangement and reorganization of the cytoskeleton, a dynamic network of filamentous proteins which provides stability and structure in a stationary context, but also facilitates directed movement by contracting. The ALP/Enigma family proteins are a diverse group of docking proteins found in numerous cellular milieus and facilitate these processes among others. In vertebrates, they are characterized by having a PDZ domain in combination with one or three LIM domains. The family is comprised of CLP-36 (PDLIM1), Mystique (PDLIM2), ALP (PDLIM3), RIL (PDLIM4), ENH (PDLIM5), ZASP (PDLIM6), and Enigma (PDLIM7). In this review, we will outline the evolution and function of their protein domains which confers their versatility. Additionally, we highlight their role in different cellular environments, focusing specifically on recent advances in muscle research using Drosophila as a model organism. Finally, we show the relevance of this protein family to human myopathies and the development of muscle-related diseases.}, } @article {pmid36529400, year = {2023}, author = {Liu, Y and Cao, M and Yan, X and Cai, X and Li, Y and Li, C and Xue, T}, title = {Genome-wide identification of gap junction (connexins and pannexins) genes in black rockfish (Sebastes schlegelii): Evolution and immune response mechanism following challenge.}, journal = {Fish & shellfish immunology}, volume = {132}, number = {}, pages = {108492}, doi = {10.1016/j.fsi.2022.108492}, pmid = {36529400}, issn = {1095-9947}, mesh = {Animals ; *Connexins/genetics ; Phylogeny ; Gap Junctions/chemistry/metabolism ; *Perciformes/metabolism ; Immunity ; }, abstract = {Cell-to-cell communication through gap junction channels is very important to coordinate the functions of cells in all multicellular biological tissues. It allows the direct exchange of ions and small molecules (including second messengers, such as Ca[2+], IP3, cyclic nucleotides, and oligonucleotides). In this study, a total of 48 members of the gap junction (GJ) protein family were identified from Sebastes schlegelii. In S. schlegelii, GJ proteins were classified into two types, connexin, and pannexin, and then connexins were divided into five subfamilies. The naming of 48 genes was verified through phylogenetic analysis and syntenic analysis. The connexin proteins contained four transmembrane fragments and two extracellular loops, the lengths of the intracellular loop and C-terminal was quite different, and the C-terminal region was highly variable after post-translational modification. PPI analysis showed that GJs interacted with tight junctions, adhesive junctions, and cell adhesions to form a complex network and participated in cell-cell junction organization, ATP binding, ion channel, voltage-gated conduction, wnt signaling pathway, Fc-γ receptor signaling pathway, and DNA replication. In addition, the S. schlegelii GJ protein was highly expressed in intestinal tissues and remarkably regulated after Edwardsiella tarda and Streptococcus iniae infection. The expression of GJs in intestinal cells of S. schlegelii was significantly regulated by LPS and poly (I:C), which was consistent with the results of intestinal tissue stimulation by pathogens. In conclusion, this study can provide valuable information for further research on the function of S. schlegelii GJ proteins.}, } @article {pmid36526191, year = {2023}, author = {Barbosa, FAS and Brait, LAS and Coutinho, FH and Ferreira, CM and Moreira, EF and de Queiroz Salles, L and Meirelles, PM}, title = {Ecological landscape explains aquifers microbial structure.}, journal = {The Science of the total environment}, volume = {862}, number = {}, pages = {160822}, doi = {10.1016/j.scitotenv.2022.160822}, pmid = {36526191}, issn = {1879-1026}, mesh = {Humans ; *Groundwater/chemistry ; Bacteria/metabolism ; Water Quality ; Gram-Negative Bacteria ; *Microbiota ; }, abstract = {Aquifers have significant social, economic, and ecological importance. They supply 30 % of the freshwater for human consumption worldwide, including agricultural and industrial use. Despite aquifers' importance, the relationships between aquifer categories and their inhabiting microbial communities are still unknown. Characterizing variations within microbial communities' function and taxonomy structure at different aquifers could give a panoramic view of patterns that may enable the detection and prediction of environmental impact caused by multiple sources. Using publicly available shotgun metagenomic datasets, we examined whether soil properties, land use, and climate variables would have a more significant influence on the taxonomy and functional structure of the microbial communities than the ecological landscapes of the aquifer (i.e., Karst, Porous, Saline, Geyser, and Porous Contaminated). We found that these categories are stronger predictors of microbial communities' structure than geographical localization. In addition, our results show that microbial richness and dominance patterns are the opposite of those found in multicellular life, where extreme habitats harbour richer functional and taxonomic microbial communities. We found that low-abundant and recently described candidate taxa, such as the chemolithoautotrophic genus Candidatus Altiarcheum and the Candidate phylum Parcubacteria, are the main contributors to aquifer microbial communities' dissimilarities. Genes related to gram-negative bacteria proteins, cell wall structures, and phage activity were the primary contributors to aquifer microbial communities' dissimilarities among the aquifers' ecological landscapes. The results reported in the present study highlight the utility of using ecological landscapes for investigating aquifer microbial communities. In addition, we suggest that functions played by recently described and low abundant bacterial groups need further investigation once they might affect water quality, geochemical cycles, and the effects of anthropogenic disturbances such as pollution and climatic events on aquifers.}, } @article {pmid36523555, year = {2022}, author = {Hogg, DW and Reid, AL and Dodsworth, TL and Chen, Y and Reid, RM and Xu, M and Husic, M and Biga, PR and Slee, A and Buck, LT and Barsyte-Lovejoy, D and Locke, M and Lovejoy, DA}, title = {Skeletal muscle metabolism and contraction performance regulation by teneurin C-terminal-associated peptide-1.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {1031264}, pmid = {36523555}, issn = {1664-042X}, abstract = {Skeletal muscle regulation is responsible for voluntary muscular movement in vertebrates. The genes of two essential proteins, teneurins and latrophilins (LPHN), evolving in ancestors of multicellular animals form a ligand-receptor pair, and are now shown to be required for skeletal muscle function. Teneurins possess a bioactive peptide, termed the teneurin C-terminal associated peptide (TCAP) that interacts with the LPHNs to regulate skeletal muscle contractility strength and fatigue by an insulin-independent glucose importation mechanism in rats. CRISPR-based knockouts and siRNA-associated knockdowns of LPHN-1 and-3 in the C2C12 mouse skeletal cell line shows that TCAP stimulates an LPHN-dependent cytosolic Ca[2+] signal transduction cascade to increase energy metabolism and enhance skeletal muscle function via increases in type-1 oxidative fiber formation and reduce the fatigue response. Thus, the teneurin/TCAP-LPHN system is presented as a novel mechanism that regulates the energy requirements and performance of skeletal muscle.}, } @article {pmid36510137, year = {2022}, author = {Hao, J and Liang, Y and Ping, J and Li, J and Shi, W and Su, Y and Wang, T}, title = {Chloroplast gene expression level is negatively correlated with evolutionary rates and selective pressure while positively with codon usage bias in Ophioglossum vulgatum L.}, journal = {BMC plant biology}, volume = {22}, number = {1}, pages = {580}, pmid = {36510137}, issn = {1471-2229}, support = {31872670//National Natural Science Foundation of China/ ; 32071781//National Natural Science Foundation of China/ ; 31670200//National Natural Science Foundation of China/ ; 31770587//National Natural Science Foundation of China/ ; }, mesh = {*Genes, Chloroplast ; Codon Usage ; Codon/genetics ; *Genome, Chloroplast/genetics ; Biological Evolution ; }, abstract = {BACKGROUND: Characterization of the key factors determining gene expression level has been of significant interest. Previous studies on the relationship among evolutionary rates, codon usage bias, and expression level mostly focused on either nuclear genes or unicellular/multicellular organisms but few in chloroplast (cp) genes. Ophioglossum vulgatum is a unique fern and has important scientific and medicinal values. In this study, we sequenced its cp genome and transcriptome to estimate the evolutionary rates (dN and dS), selective pressure (dN/dS), gene expression level, codon usage bias, and their correlations.

RESULTS: The correlation coefficients between dN, dS, and dN/dS, and Transcripts Per Million (TPM) average values were -0.278 (P = 0.027 < 0.05), -0.331 (P = 0.008 < 0.05), and -0.311 (P = 0.013 < 0.05), respectively. The codon adaptation index (CAI) and tRNA adaptation index (tAI) were significantly positively correlated with TPM average values (P < 0.05).

CONCLUSIONS: Our results indicated that when the gene expression level was higher, the evolutionary rates and selective pressure were lower, but the codon usage bias was stronger. We provided evidence from cp gene data which supported the E-R (E stands for gene expression level and R stands for evolutionary rate) anti-correlation.}, } @article {pmid36506100, year = {2022}, author = {Wright, BA and Kvansakul, M and Schierwater, B and Humbert, PO}, title = {Cell polarity signalling at the birth of multicellularity: What can we learn from the first animals.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {1024489}, pmid = {36506100}, issn = {2296-634X}, abstract = {The innovation of multicellularity has driven the unparalleled evolution of animals (Metazoa). But how is a multicellular organism formed and how is its architecture maintained faithfully? The defining properties and rules required for the establishment of the architecture of multicellular organisms include the development of adhesive cell interactions, orientation of division axis, and the ability to reposition daughter cells over long distances. Central to all these properties is the ability to generate asymmetry (polarity), coordinated by a highly conserved set of proteins known as cell polarity regulators. The cell polarity complexes, Scribble, Par and Crumbs, are considered to be a metazoan innovation with apicobasal polarity and adherens junctions both believed to be present in all animals. A better understanding of the fundamental mechanisms regulating cell polarity and tissue architecture should provide key insights into the development and regeneration of all animals including humans. Here we review what is currently known about cell polarity and its control in the most basal metazoans, and how these first examples of multicellular life can inform us about the core mechanisms of tissue organisation and repair, and ultimately diseases of tissue organisation, such as cancer.}, } @article {pmid36505058, year = {2022}, author = {Alarcón, ME and Polo, PG and Akyüz, SN and Rafiqi, AM}, title = {Evolution and ontogeny of bacteriocytes in insects.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {1034066}, pmid = {36505058}, issn = {1664-042X}, abstract = {The ontogenetic origins of the bacteriocytes, which are cells that harbour bacterial intracellular endosymbionts in multicellular animals, are unknown. During embryonic development, a series of morphological and transcriptional changes determine the fate of distinct cell types. The ontogeny of bacteriocytes is intimately linked with the evolutionary transition of endosymbionts from an extracellular to an intracellular environment, which in turn is linked to the diet of the host insect. Here we review the evolution and development of bacteriocytes in insects. We first classify the endosymbiotic occupants of bacteriocytes, highlighting the complex challenges they pose to the host. Then, we recall the historical account of the discovery of bacteriocytes. We then summarize the molecular interactions between the endosymbiont and the host. In addition, we illustrate the genetic contexts in which the bacteriocytes develop, with examples of the genetic changes in the hosts and endosymbionts, during specific endosymbiotic associations. We finally address the evolutionary origin as well as the putative ontogenetic or developmental source of bacteriocytes in insects.}, } @article {pmid36499258, year = {2022}, author = {Vainshelbaum, NM and Giuliani, A and Salmina, K and Pjanova, D and Erenpreisa, J}, title = {The Transcriptome and Proteome Networks of Malignant Tumours Reveal Atavistic Attractors of Polyploidy-Related Asexual Reproduction.}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, pmid = {36499258}, issn = {1422-0067}, support = {1.1.1.2/VIAA/3/19/463//European Regional Development Fund/ ; 8.2.2.0/20/I/006//European Social Fund/ ; }, mesh = {Animals ; Humans ; *Gene Duplication ; Genome, Plant ; Proteome/genetics ; Evolution, Molecular ; Polyploidy ; Transcriptome ; *Neoplasms/genetics ; Mammals/genetics ; }, abstract = {The expression of gametogenesis-related (GG) genes and proteins, as well as whole genome duplications (WGD), are the hallmarks of cancer related to poor prognosis. Currently, it is not clear if these hallmarks are random processes associated only with genome instability or are programmatically linked. Our goal was to elucidate this via a thorough bioinformatics analysis of 1474 GG genes in the context of WGD. We examined their association in protein-protein interaction and coexpression networks, and their phylostratigraphic profiles from publicly available patient tumour data. The results show that GG genes are upregulated in most WGD-enriched somatic cancers at the transcriptome level and reveal robust GG gene expression at the protein level, as well as the ability to associate into correlation networks and enrich the reproductive modules. GG gene phylostratigraphy displayed in WGD+ cancers an attractor of early eukaryotic origin for DNA recombination and meiosis, and one relative to oocyte maturation and embryogenesis from early multicellular organisms. The upregulation of cancer-testis genes emerging with mammalian placentation was also associated with WGD. In general, the results suggest the role of polyploidy for soma-germ transition accessing latent cancer attractors in the human genome network, which appear as pre-formed along the whole Evolution of Life.}, } @article {pmid36497057, year = {2022}, author = {Aktas, RG and Karski, M and Issac, B and Sun, L and Rockowitz, S and Sliz, P and Vakili, K}, title = {Long-Term Characteristics of Human-Derived Biliary Organoids under a Single Continuous Culture Condition.}, journal = {Cells}, volume = {11}, number = {23}, pages = {}, pmid = {36497057}, issn = {2073-4409}, support = {N/A//CHMC Surgical Foundation/ ; }, mesh = {Humans ; Child ; *Organoids ; *Epithelial Cells ; }, abstract = {Organoids have been used to investigate the three-dimensional (3D) organization and function of their respective organs. These self-organizing 3D structures offer a distinct advantage over traditional two-dimensional (2D) culture techniques by creating a more physiologically relevant milieu to study complex biological systems. The goal of this study was to determine the feasibility of establishing organoids from various pediatric liver diseases and characterize the long-term evolution of cholangiocyte organoids (chol-orgs) under a single continuous culture condition. We established chol-orgs from 10 different liver conditions and characterized their multicellular organization into complex epithelial structures through budding, merging, and lumen formation. Immunofluorescent staining, electron microscopy, and single-nucleus RNA (snRNA-seq) sequencing confirmed the cholangiocytic nature of the chol-orgs. There were significant cell population differences in the transcript profiles of two-dimensional and organoid cultures based on snRNA-seq. Our study provides an approach for the generation and long-term maintenance of chol-orgs from various pediatric liver diseases under a single continuous culture condition.}, } @article {pmid36494694, year = {2022}, author = {Sun, H and Fang, T and Wang, T and Yu, Z and Gong, L and Wei, X and Wang, H and He, Y and Liu, L and Yan, Y and Sui, W and Xu, Y and Yi, S and Qiu, L and Hao, M}, title = {Single-cell profiles reveal tumor cell heterogeneity and immunosuppressive microenvironment in Waldenström macroglobulinemia.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {576}, pmid = {36494694}, issn = {1479-5876}, mesh = {Humans ; *Ecosystem ; *Waldenstrom Macroglobulinemia/genetics/pathology ; Bone Marrow/pathology ; Tumor Microenvironment ; B-Lymphocytes/pathology ; }, abstract = {BACKGROUND: Waldenström macroglobulinemia (WM) is a rare and incurable indolent B-cell malignancy. The molecular pathogenesis and the role of immunosuppressive microenvironment in WM development are still incompletely understood.

METHODS: The multicellular ecosystem in bone marrow (BM) of WM were delineated by single-cell RNA-sequencing (scRNA-seq) and investigated the underlying molecular characteristics.

RESULTS: Our data uncovered the heterogeneity of malignant cells in WM, and investigated the kinetic co-evolution of WM and immune cells, which played pivotal roles in disease development and progression. Two novel subpopulations of malignant cells, CD19[+]CD3[+] and CD138[+]CD3[+], co-expressing T-cell marker genes were identified at single-cell resolution. Pseudotime-ordered analysis elucidated that CD19[+]CD3[+] malignant cells presented at an early stage of WM-B cell differentiation. Colony formation assay further identified that CD19[+]CD3[+] malignant cells acted as potential WM precursors. Based on the findings of T cell marker aberrant expressed on WM tumor cells, we speculate the long-time activation of tumor antigen-induced immunosuppressive microenvironment that is involved in the pathogenesis of WM. Therefore, our study further investigated the possible molecular mechanism of immune cell dysfunction. A precursor exhausted CD8-T cells and functional deletion of NK cells were identified in WM, and CD47 would be a potential therapeutic target to reverse the dysfunction of immune cells.

CONCLUSIONS: Our study facilitates further understanding of the biological heterogeneity of tumor cells and immunosuppressive microenvironment in WM. These data may have implications for the development of novel immunotherapies, such as targeting pre-exhausted CD8-T cells in WM.}, } @article {pmid36477143, year = {2022}, author = {La Fortezza, M and Rendueles, O and Keller, H and Velicer, GJ}, title = {Author Correction: Hidden paths to endless forms most wonderful: ecology latently shapes evolution of multicellular development in predatory bacteria.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {1342}, doi = {10.1038/s42003-022-04312-w}, pmid = {36477143}, issn = {2399-3642}, } @article {pmid36476840, year = {2022}, author = {Nakabachi, A and Inoue, H and Hirose, Y}, title = {High-resolution Microbiome Analyses of Nine Psyllid Species of the Family Triozidae Identified Previously Unrecognized but Major Bacterial Populations, including Liberibacter and Wolbachia of Supergroup O.}, journal = {Microbes and environments}, volume = {37}, number = {4}, pages = {}, pmid = {36476840}, issn = {1347-4405}, mesh = {Humans ; Animals ; Liberibacter ; *Wolbachia/genetics ; *Hemiptera ; RNA, Ribosomal, 16S/genetics ; Europe ; }, abstract = {Psyllids (Hemiptera: Sternorrhyncha: Psylloidea) are plant sap-sucking insects that include important agricultural pests. To obtain insights into the ecological and evolutionary behaviors of microbes, including plant pathogens, in Psylloidea, high-resolution ana-lyses of the microbiomes of nine psyllid species belonging to the family Triozidae were performed using high-throughput amplicon sequencing of the 16S rRNA gene. Analyses identified various bacterial populations, showing that all nine psyllids have at least one secondary symbiont, along with the primary symbiont "Candidatus Carsonella ruddii" (Gammaproteobacteria: Oceanospirillales: Halomonadaceae). The majority of the secondary symbionts were gammaproteobacteria, particularly those of the order Enterobacterales, which included Arsenophonus and Serratia symbiotica, a bacterium formerly recognized only as a secondary symbiont of aphids (Hemiptera: Sternorrhyncha: Aphidoidea). The non-Enterobacterales gammaproteobacteria identified in the present study were Diplorickettsia (Diplorickettsiales: Diplorickettsiaceae), a potential human pathogen, and Carnimonas (Oceanospirillales: Halomonadaceae), a lineage detected for the first time in Psylloidea. Regarding alphaproteobacteria, the potential plant pathogen "Ca. Liberibacter europaeus" (Rhizobiales: Rhizobiaceae) was detected for the first time in Epitrioza yasumatsui, which feeds on the Japanese silverberry Elaeagnus umbellata (Elaeagnaceae), an aggressive invasive plant in the United States and Europe. Besides the detection of Wolbachia (Rickettsiales: Anaplasmataceae) of supergroup B in three psyllid species, a lineage belonging to supergroup O was identified for the first time in Psylloidea. These results suggest the rampant transfer of bacterial symbionts among animals and plants, thereby providing deeper insights into the evolution of interkingdom interactions among multicellular organisms and bacteria, which will facilitate the control of pest psyllids.}, } @article {pmid36469777, year = {2022}, author = {Zhang, DQ and Chen, PC and Li, ZY and Zhang, R and Li, B}, title = {Topological defect-mediated morphodynamics of active-active interfaces.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {50}, pages = {e2122494119}, pmid = {36469777}, issn = {1091-6490}, mesh = {*Liquid Crystals/chemistry ; Computer Simulation ; }, abstract = {Physical interfaces widely exist in nature and engineering. Although the formation of passive interfaces is well elucidated, the physical principles governing active interfaces remain largely unknown. Here, we combine simulation, theory, and cell-based experiment to investigate the evolution of an active-active interface. We adopt a biphasic framework of active nematic liquid crystals. We find that long-lived topological defects mechanically energized by activity display unanticipated dynamics nearby the interface, where defects perform "U-turns" to keep away from the interface, push the interface to develop local fingers, or penetrate the interface to enter the opposite phase, driving interfacial morphogenesis and cross-interface defect transport. We identify that the emergent interfacial morphodynamics stems from the instability of the interface and is further driven by the activity-dependent defect-interface interactions. Experiments of interacting multicellular monolayers with extensile and contractile differences in cell activity have confirmed our predictions. These findings reveal a crucial role of topological defects in active-active interfaces during, for example, boundary formation and tissue competition that underlie organogenesis and clinically relevant disorders.}, } @article {pmid36468669, year = {2022}, author = {Colizzi, ES and Hogeweg, P and Vroomans, RMA}, title = {Modelling the evolution of novelty: a review.}, journal = {Essays in biochemistry}, volume = {66}, number = {6}, pages = {727-735}, pmid = {36468669}, issn = {1744-1358}, abstract = {Evolution has been an inventive process since its inception, about 4 billion years ago. It has generated an astounding diversity of novel mechanisms and structures for adaptation to the environment, for competition and cooperation, and for organisation of the internal and external dynamics of the organism. How does this novelty come about? Evolution builds with the tools available, and on top of what it has already built - therefore, much novelty consists in repurposing old functions in a different context. In the process, the tools themselves evolve, allowing yet more novelty to arise. Despite evolutionary novelty being the most striking observable of evolution, it is not accounted for in classical evolutionary theory. Nevertheless, mathematical and computational models that illustrate mechanisms of evolutionary innovation have been developed. In the present review, we present and compare several examples of computational evo-devo models that capture two aspects of novelty: 'between-level novelty' and 'constructive novelty.' Novelty can evolve between predefined levels of organisation to dynamically transcode biological information across these levels - as occurs during development. Constructive novelty instead generates a level of biological organisation by exploiting the lower level as an informational scaffold to open a new space of possibilities - an example being the evolution of multicellularity. We propose that the field of computational evo-devo is well-poised to reveal many more exciting mechanisms for the evolution of novelty. A broader theory of evolutionary novelty may well be attainable in the near future.}, } @article {pmid36460873, year = {2022}, author = {Niculescu, VF}, title = {A comment on the article Jaques et al. "Origin and evolution of animal multicellularity in light of phylogenomics and cancer genetics ".}, journal = {Medical oncology (Northwood, London, England)}, volume = {40}, number = {1}, pages = {38}, pmid = {36460873}, issn = {1559-131X}, mesh = {Animals ; Humans ; Phylogeny ; *Health Personnel ; *Neoplasms/genetics ; }, abstract = {For developmental biologists, the work of Jaques et al. is quite surprising. It suggests that cancer genetics and cancer phylogenomics may contribute to the origin and evolution of multicellularity in animals. My commentary complements the work of Jaques et al. from the perspective of evolutionary life cycle biology and recalls the statement of Douglas H. Erwin, who said that understanding life cycle evolution is (equally) crucial to subsequent steps [1].}, } @article {pmid36449319, year = {2022}, author = {Baker, EA and Woollard, A}, title = {The road less travelled? Exploring the nuanced evolutionary consequences of duplicated genes.}, journal = {Essays in biochemistry}, volume = {66}, number = {6}, pages = {737-744}, pmid = {36449319}, issn = {1744-1358}, abstract = {Duplicated genes have long been appreciated as both substrates and catalysts of evolutionary processes. From even the simplest cell to complex multicellular animals and plants, duplicated genes have made immeasurable contributions to the phenotypic evolution of all life on Earth. Not merely drivers of morphological innovation and speciation events, however, gene duplications sculpt the evolution of genetic architecture in ways we are only just coming to understand now we have the experimental tools to do so. As such, the present article revisits our understanding of the ways in which duplicated genes evolve, examining closely the various fates they can adopt in light of recent work that yields insights from studies of paralogues from across the tree of life that challenge the classical framework.}, } @article {pmid36447160, year = {2022}, author = {Liu, Y and Ma, Y and Aray, H and Lan, H}, title = {Morphogenesis and cell wall composition of trichomes and their function in response to salt in halophyte Salsola ferganica.}, journal = {BMC plant biology}, volume = {22}, number = {1}, pages = {551}, pmid = {36447160}, issn = {1471-2229}, support = {31960037//National Natural Science Foundation of China/ ; }, mesh = {*Salsola ; Salt-Tolerant Plants/genetics ; Trichomes ; *Arabidopsis/genetics ; Sodium Chloride ; Cell Wall ; Morphogenesis ; Gossypium ; }, abstract = {BACKGROUND: To survive harsh environmental conditions, desert plants show various adaptions, such as the evolution of trichomes, which are protective epidermal protrusions. Currently, the morphogenesis and function of trichomes in desert plants are not well understood. Salsola ferganica is an annual halophyte distributed in cold deserts; at the seedling stage, its rod-shaped true leaves are covered with long and thick trichomes and are affected by habitat conditions. Therefore, we evaluated the trichomes on morphogenesis and cell wall composition of S. ferganica compared to Arabidopsis thaliana and cotton, related gene expression, and preliminary function in salt accumulation of the leaves.

RESULTS: The trichomes of S. ferganica were initiated from the epidermal primordium, followed by two to three rounds of cell division to form a multicellular trichome, while some genes associated with them were positively involved. Cell wall composition analysis showed that different polysaccharides including heavily methyl-esterified and fully de-esterified pectins (before maturation, probably in the primary wall), xyloglucans (in the mid-early and middle stages, probably in the secondary wall), and extensin (during the whole developmental period) were detected, which were different from those found in trichomes of Arabidopsis and cotton. Moreover, trichome development was affected by abiotic stress, and might accumulate salt from the mesophyll cells and secrete outside.

CONCLUSIONS: S. ferganica has multicellular, non-branched trichomes that undergo two to three rounds of cell division and are affected by abiotic stress. They have a unique cell wall composition which is different from that of Arabidopsis and cotton. Furthermore, several genes positively or negatively regulate trichome development. Our findings should contribute to our further understanding of the biogenesis and adaptation of plant accessory structures in desert plant species.}, } @article {pmid36434792, year = {2022}, author = {Zhan, A and Luo, Y and Qin, H and Lin, W and Tian, L}, title = {Hypomagnetic Field Exposure Affecting Gut Microbiota, Reactive Oxygen Species Levels, and Colonic Cell Proliferation in Mice.}, journal = {Bioelectromagnetics}, volume = {43}, number = {8}, pages = {462-475}, doi = {10.1002/bem.22427}, pmid = {36434792}, issn = {1521-186X}, support = {42074073//National Natural Science Foundation of China/ ; 41621004//National Natural Science Foundation of China/ ; XDA17010501//Strategic Priority Research Program of the Chinese Academy of Sciences/ ; }, mesh = {Animals ; Mice ; Cell Proliferation ; *Colon ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; *Reactive Oxygen Species ; }, abstract = {The gut microbiota has been considered one of the key factors in host health, which is influenced by many environmental factors. The geomagnetic field (GMF) represents one of the important environmental conditions for living organisms. Previous studies have shown that the elimination of GMF, the so-called hypomagnetic field (HMF), could affect the physiological functions and resistance to antibiotics of some microorganisms. However, whether long-term HMF exposure could alter the gut microbiota to some extent in mammals remains unclear. Here, we investigated the effects of long-term (8- and 12-week) HMF exposure on the gut microbiota in C57BL/6J mice. Our results clearly showed that 8-week HMF significantly affected the diversity and function of the mouse gut microbiota. Compared with the GMF group, the concentrations of short-chain fatty acids tended to decrease in the HMF group. Immunofluorescence analysis showed that HMF promoted colonic cell proliferation, concomitant with an increased level of reactive oxygen species (ROS). To our knowledge, this is the first in vivo finding that long-term HMF exposure could affect the mouse gut microbiota, ROS levels, and colonic cell proliferation in the colon. Moreover, the changes in gut microbiota can be restored by returning mice to the GMF environment, thus the possible harm to the microbiota caused by HMF exposure can be alleviated. © 2022 Bioelectromagnetics Society.}, } @article {pmid36433975, year = {2022}, author = {Kreider, JJ and Janzen, T and Bernadou, A and Elsner, D and Kramer, BH and Weissing, FJ}, title = {Resource sharing is sufficient for the emergence of division of labour.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {7232}, pmid = {36433975}, issn = {2041-1723}, mesh = {Animals ; Female ; Pregnancy ; *Biological Evolution ; *Labor, Obstetric ; }, abstract = {Division of labour occurs in a broad range of organisms. Yet, how division of labour can emerge in the absence of pre-existing interindividual differences is poorly understood. Using a simple but realistic model, we show that in a group of initially identical individuals, division of labour emerges spontaneously if returning foragers share part of their resources with other group members. In the absence of resource sharing, individuals follow an activity schedule of alternating between foraging and other tasks. If non-foraging individuals are fed by other individuals, their alternating activity schedule becomes interrupted, leading to task specialisation and the emergence of division of labour. Furthermore, nutritional differences between individuals reinforce division of labour. Such differences can be caused by increased metabolic rates during foraging or by dominance interactions during resource sharing. Our model proposes a plausible mechanism for the self-organised emergence of division of labour in animal groups of initially identical individuals. This mechanism could also play a role for the emergence of division of labour during the major evolutionary transitions to eusociality and multicellularity.}, } @article {pmid36430514, year = {2022}, author = {Ojosnegros, S and Alvarez, JM and Grossmann, J and Gagliardini, V and Quintanilla, LG and Grossniklaus, U and Fernández, H}, title = {The Shared Proteome of the Apomictic Fern Dryopteris affinis ssp. affinis and Its Sexual Relative Dryopteris oreades.}, journal = {International journal of molecular sciences}, volume = {23}, number = {22}, pages = {}, pmid = {36430514}, issn = {1422-0067}, support = {//University of Zurich/ ; Grant CESSTT1819 for International Mobility of Research Staff//University of Oviedo/ ; PRIME-XS-0002520//European Union's 7th Framework Program/ ; }, mesh = {*Dryopteris/genetics ; *Ferns/genetics ; Proteome ; Proteomics ; Plant Growth Regulators ; }, abstract = {Ferns are a diverse evolutionary lineage, sister to the seed plants, which is of great ecological importance and has a high biotechnological potential. Fern gametophytes represent one of the simplest autotrophic, multicellular plant forms and show several experimental advantages, including a simple and space-efficient in vitro culture system. However, the molecular basis of fern growth and development has hardly been studied. Here, we report on a proteomic study that identified 417 proteins shared by gametophytes of the apogamous fern Dryopteris affinis ssp. affinis and its sexual relative Dryopteris oreades. Most proteins are predicted to localize to the cytoplasm, the chloroplast, or the nucleus, and are linked to enzymatic, binding, and structural activities. A subset of 145 proteins are involved in growth, reproduction, phytohormone signaling and biosynthesis, and gene expression, including homologs of SHEPHERD (SHD), HEAT SHOCK PROTEIN 90-5 (CR88), TRP4, BOBBER 1 (BOB1), FLAVONE 3'-O-METHYLTRANSFERASE 1 (OMT1), ZEAXANTHIN EPOXIDASE (ABA1), GLUTAMATE DESCARBOXYLASE 1 (GAD), and dsRNA-BINDING DOMAIN-LIKE SUPERFAMILY PROTEIN (HLY1). Nearly 25% of the annotated proteins are associated with responses to biotic and abiotic stimuli. As for biotic stress, the proteins PROTEIN SGT1 HOMOLOG B (SGT1B), SUPPRESSOR OF SA INSENSITIVE2 (SSI2), PHOSPHOLIPASE D ALPHA 1 (PLDALPHA1), SERINE/THREONINE-PROTEIN KINASE SRK2E (OST1), ACYL CARRIER PROTEIN 4 (ACP4), and NONHOST RESISTANCE TO P. S. PHASEOLICOLA1 (GLPK) are worth mentioning. Regarding abiotic stimuli, we found proteins associated with oxidative stress: SUPEROXIDE DISMUTASE[CU-ZN] 1 (CSD1), and GLUTATHIONE S-TRANSFERASE U19 (GSTU19), light intensity SERINE HYDROXYMETHYLTRANSFERASE 1 (SHM1) and UBIQUITIN-CONJUGATING ENZYME E2 35 (UBC35), salt and heavy metal stress included MITOCHONDRIAL PHOSPHATE CARRIER PROTEIN 3 (PHT3;1), as well as drought and thermotolerance: LEA7, DEAD-BOX ATP-DEPENDENT RNA HELICASE 38 (LOS4), and abundant heat-shock proteins and other chaperones. In addition, we identified interactomes using the STRING platform, revealing protein-protein associations obtained from co-expression, co-occurrence, text mining, homology, databases, and experimental datasets. By focusing on ferns, this proteomic study increases our knowledge on plant development and evolution, and may inspire future applications in crop species.}, } @article {pmid36421702, year = {2022}, author = {Sowa, ST and Bosetti, C and Galera-Prat, A and Johnson, MS and Lehtiö, L}, title = {An Evolutionary Perspective on the Origin, Conservation and Binding Partner Acquisition of Tankyrases.}, journal = {Biomolecules}, volume = {12}, number = {11}, pages = {}, pmid = {36421702}, issn = {2218-273X}, mesh = {Humans ; Animals ; *Tankyrases/genetics/chemistry/metabolism ; Telomere Homeostasis ; Wnt Signaling Pathway ; }, abstract = {Tankyrases are poly-ADP-ribosyltransferases that regulate many crucial and diverse cellular processes in humans such as Wnt signaling, telomere homeostasis, mitotic spindle formation and glucose metabolism. While tankyrases are present in most animals, functional differences across species may exist. In this work, we confirm the widespread distribution of tankyrases throughout the branches of multicellular animal life and identify the single-celled choanoflagellates as earliest origin of tankyrases. We further show that the sequences and structural aspects of TNKSs are well-conserved even between distantly related species. We also experimentally characterized an anciently diverged tankyrase homolog from the sponge Amphimedon queenslandica and show that the basic functional aspects, such as poly-ADP-ribosylation activity and interaction with the canonical tankyrase binding peptide motif, are conserved. Conversely, the presence of tankyrase binding motifs in orthologs of confirmed interaction partners varies greatly between species, indicating that tankyrases may have different sets of interaction partners depending on the animal lineage. Overall, our analysis suggests a remarkable degree of conservation for tankyrases, and that their regulatory functions in cells have likely changed considerably throughout evolution.}, } @article {pmid36407558, year = {2022}, author = {Pandey, R and Mani, D and Shanker, K and Bawankule, DU and Chanda, D and Lal, RK and Pal, A and Khare, P and Kumar, N and Tandon, S and Saikia, D and Gupta, AK and Srivastava, RK and Kumar, S and Suresh, R and Singh, S and Kalra, A and Maurya, A and Singh, DP and Pandey, T and Trivedi, S and Smita, SS and Pant, A and Rathor, L and Asthana, J and Trivedi, M and Trivedi, PK}, title = {Towards the development of phytoextract based healthy ageing cognitive booster formulation, explored through Caenorhabditis elegans model.}, journal = {The Nucleus : an international journal of cytology and allied topics}, volume = {65}, number = {3}, pages = {303-320}, pmid = {36407558}, issn = {0029-568X}, abstract = {UNLABELLED: The positive effect of herbal supplements on aging and age-related disorders has led to the evolution of natural curatives for remedial neurodegenerative diseases in humans. The advancement in aging is exceedingly linked to oxidative stress. Enhanced oxidative stress interrupts health of humans in various ways, necessitating to find stress alleviating herbal resources. Currently, minimal scientifically validated health and cognitive booster resources are available. Therefore, we explored the impact of plant extracts in different combinations on oxidative stress, life span and cognition using the multicellular transgenic humanized C. elegans, and further validated the same in Mus musculus, besides testing their safety and toxicity. In our investigations, the final product-the HACBF (healthy ageing cognitive booster formulation) thus developed was found to reduce major aging biomarkers like lipofuscin, protein carbonyl, lipid levels and enhanced activity of antioxidant enzymes. Further confirmation was done using transgenic worms and RT-PCR. The cognitive boosting activities analyzed in C. elegans and M. musculus model system were found to be at par with donepezil and L-dopa, the two drugs which are commonly used to treat Parkinson's and Alzheimer's diseases. In the transgenic C. elegans model system, the HACBF exhibited reduced aggregation of misfolded disease proteins α-synuclein and increased the health of nicotinic acetylcholine receptor, levels of Acetylcholine and Dopamine contents respectively, the major neurotransmitters responsible for memory, language, learning behavior and movement. Molecular studies clearly indicate that HACBF upregulated major genes responsible for healthy aging and cognitive booster activities in C. elegans and as well as in M. musculus. As such, the present herbal product thus developed may be quite useful for healthy aging and cognitive boosting activities, and more so during this covid-19 pandemic.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13237-022-00407-1.}, } @article {pmid36404107, year = {2023}, author = {Sepp, T and Giraudeau, M}, title = {Wild animals as an underused treasure trove for studying the genetics of cancer.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {2}, pages = {e2200188}, doi = {10.1002/bies.202200188}, pmid = {36404107}, issn = {1521-1878}, mesh = {Animals ; Humans ; *Animals, Wild/genetics ; Ecology ; Biodiversity ; *Neoplasms/genetics ; Genomics ; }, abstract = {Recent years have seen an emergence of the field of comparative cancer genomics. However, the advancements in this field are held back by the hesitation to use knowledge obtained from human studies to study cancer in other animals, and vice versa. Since cancer is an ancient disease that arose with multicellularity, oncogenes and tumour-suppressor genes are amongst the oldest gene classes, shared by most animal species. Acknowledging that other animals are, in terms of cancer genetics, ecology, and evolution, rather similar to humans, creates huge potential for advancing the fields of human and animal oncology, but also biodiversity conservation. Also see the video abstract here: https://youtu.be/UFqyMx5HETY.}, } @article {pmid36386690, year = {2022}, author = {Rodríguez-Rojas, A and Rolff, J}, title = {Antimicrobial activity of cationic antimicrobial peptides against stationary phase bacteria.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1029084}, pmid = {36386690}, issn = {1664-302X}, abstract = {Antimicrobial peptides (AMPs) are ancient antimicrobial weapons used by multicellular organisms as components of their innate immune defenses. Because of the antibiotic crisis, AMPs have also become candidates for developing new drugs. Here, we show that five different AMPs of different classes are effective against non-dividing Escherichia coli and Staphylococcus aureus. By comparison, three conventional antibiotics from the main three classes of antibiotics poorly kill non-dividing bacteria at clinically relevant doses. The killing of fast-growing bacteria by AMPs is faster than that of slow-dividing bacteria and, in some cases, without any difference. Still, non-dividing bacteria are effectively killed over time. Our results point to a general property of AMPs, which might explain why selection has favored AMPs in the evolution of metazoan immune systems. The ability to kill non-dividing cells is another reason that makes AMPs exciting candidates for drug development.}, } @article {pmid36384644, year = {2022}, author = {Pinskey, JM and Lagisetty, A and Gui, L and Phan, N and Reetz, E and Tavakoli, A and Fu, G and Nicastro, D}, title = {Three-dimensional flagella structures from animals' closest unicellular relatives, the Choanoflagellates.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36384644}, issn = {2050-084X}, support = {F32 GM137470/GM/NIGMS NIH HHS/United States ; R01 GM083122/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Choanoflagellata/metabolism ; Cryoelectron Microscopy ; Flagella ; Axoneme ; Cilia ; }, abstract = {In most eukaryotic organisms, cilia and flagella perform a variety of life-sustaining roles related to environmental sensing and motility. Cryo-electron microscopy has provided considerable insight into the morphology and function of flagellar structures, but studies have been limited to less than a dozen of the millions of known eukaryotic species. Ultrastructural information is particularly lacking for unicellular organisms in the Opisthokonta clade, leaving a sizeable gap in our understanding of flagella evolution between unicellular species and multicellular metazoans (animals). Choanoflagellates are important aquatic heterotrophs, uniquely positioned within the opisthokonts as the metazoans' closest living unicellular relatives. We performed cryo-focused ion beam milling and cryo-electron tomography on flagella from the choanoflagellate species Salpingoeca rosetta. We show that the axonemal dyneins, radial spokes, and central pair complex in S. rosetta more closely resemble metazoan structures than those of unicellular organisms from other suprakingdoms. In addition, we describe unique features of S. rosetta flagella, including microtubule holes, microtubule inner proteins, and the flagellar vane: a fine, net-like extension that has been notoriously difficult to visualize using other methods. Furthermore, we report barb-like structures of unknown function on the extracellular surface of the flagellar membrane. Together, our findings provide new insights into choanoflagellate biology and flagella evolution between unicellular and multicellular opisthokonts.}, } @article {pmid36379956, year = {2022}, author = {Huang, J and Zhao, L and Malik, S and Gentile, BR and Xiong, V and Arazi, T and Owen, HA and Friml, J and Zhao, D}, title = {Specification of female germline by microRNA orchestrated auxin signaling in Arabidopsis.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6960}, pmid = {36379956}, issn = {2041-1723}, mesh = {*Arabidopsis/metabolism ; *Arabidopsis Proteins/metabolism ; *MicroRNAs/genetics/metabolism ; Gene Expression Regulation, Plant ; Indoleacetic Acids/metabolism ; Germ Cells/metabolism ; Transcription Factors/metabolism ; }, abstract = {Germline determination is essential for species survival and evolution in multicellular organisms. In most flowering plants, formation of the female germline is initiated with specification of one megaspore mother cell (MMC) in each ovule; however, the molecular mechanism underlying this key event remains unclear. Here we report that spatially restricted auxin signaling promotes MMC fate in Arabidopsis. Our results show that the microRNA160 (miR160) targeted gene ARF17 (AUXIN RESPONSE FACTOR17) is required for promoting MMC specification by genetically interacting with the SPL/NZZ (SPOROCYTELESS/NOZZLE) gene. Alterations of auxin signaling cause formation of supernumerary MMCs in an ARF17- and SPL/NZZ-dependent manner. Furthermore, miR160 and ARF17 are indispensable for attaining a normal auxin maximum at the ovule apex via modulating the expression domain of PIN1 (PIN-FORMED1) auxin transporter. Our findings elucidate the mechanism by which auxin signaling promotes the acquisition of female germline cell fate in plants.}, } @article {pmid36372985, year = {2022}, author = {Durbagula, S and Korlimarla, A and Ravikumar, G and Valiya Parambath, S and Kaku, SM and Visweswariah, AM}, title = {Prenatal epigenetic factors are predisposing for neurodevelopmental disorders-Considering placenta as a model.}, journal = {Birth defects research}, volume = {114}, number = {20}, pages = {1324-1342}, doi = {10.1002/bdr2.2119}, pmid = {36372985}, issn = {2472-1727}, mesh = {Animals ; Pregnancy ; Female ; *Placenta/metabolism ; *Neurodevelopmental Disorders/genetics ; Epigenomics ; Epigenesis, Genetic ; Fetal Development/physiology ; }, abstract = {The heterogeneous characteristics of neurodevelopmental disorders (NDDs) have resulted in varied perspectives on their causation. The biology behind the phenotypic heterogeneity in NDDs is not yet well-defined, but a strong genetic basis has become well accepted as causal for NDDs. Alongside this, there is growing focus on epigenetic mechanisms. The evidence mounting for in-utero origins of NDDs has promoted research focused on epigenetic mechanisms that impact genes that program early brain development. Considering that placenta is a vital organ, this review emphasizes the prenatal factors and their effects on epigenetic changes influencing the normal functioning of the placenta, and factors mediating pathology in the developing fetus. Overall, it is an attempt to bring focus on the hypothesis that "Prenatal epigenetic factors in the placenta could be predisposing to NDDs (with special interest on autism spectrum disorders)." This review finds growing evidence for epigenetic modifications in the placenta that affect glucocorticoid, nutrient, and immune signaling pathways, eventually impacting fetal brain development. This evidence largely comes from animal models. Given the multicellular nature of placenta, we conclude that, there is a need for placental research focused on employing single-cell approaches and genome-wide methylation profiles to bring insights into specific molecular pathways in the placenta that regulate early brain development.}, } @article {pmid36366977, year = {2023}, author = {Yu, L and Stachowicz, JJ and DuBois, K and Reusch, TBH}, title = {Detecting clonemate pairs in multicellular diploid clonal species based on a shared heterozygosity index.}, journal = {Molecular ecology resources}, volume = {23}, number = {3}, pages = {592-600}, doi = {10.1111/1755-0998.13736}, pmid = {36366977}, issn = {1755-0998}, support = {201704910807//China Scholarship Council/ ; RGP0042_2020//Human Frontiers of Science Program/ ; }, mesh = {Animals ; *Diploidy ; Heterozygote ; *Genome ; Reproduction ; Genetic Loci ; }, abstract = {Clonal reproduction, the formation of nearly identical individuals via mitosis in the absence of genetic recombination, is a very common reproductive mode across plants, fungi and animals. To detect clonal genetic structure, genetic similarity indices based on shared alleles are widely used, such as the Jaccard index, or identity by state. Here we propose a new pairwise genetic similarity index, the SH index, based on segregating genetic marker loci (typically single nucleotide polymorphisms) that are identically heterozygous for pairs of samples (NSH). To test our method, we analyse two old seagrass clones (Posidonia australis, estimated to be around 8500 years old; Zostera marina, >750 years old) along with two young Z. marina clones of known age (17 years old). We show that focusing on shared heterozygosity amplifies the power to distinguish sample pairs belonging to different clones compared to methods focusing on all shared alleles. Our proposed workflow can successfully detect clonemates at a location dominated by a single clone. When the collected samples involve two or more clones, the SH index shows a clear gap between clonemate pairs and interclone sample pairs. Ideally NSH should be on the order of approximately ≥3000, a number easily achievable via restriction-site associated DNA (RAD) sequencing or whole-genome resequencing. Another potential application of the SH index is to detect possible parent-descendant pairs under selfing. Our proposed workflow takes advantage of the availability of the larger number of genetic markers in the genomic era, and improves the ability to distinguish clonemates from nonclonemates in multicellular diploid clonal species.}, } @article {pmid36356576, year = {2022}, author = {Peterson, AF and Ingram, K and Huang, EJ and Parksong, J and McKenney, C and Bever, GS and Regot, S}, title = {Systematic analysis of the MAPK signaling network reveals MAP3K-driven control of cell fate.}, journal = {Cell systems}, volume = {13}, number = {11}, pages = {885-894.e4}, pmid = {36356576}, issn = {2405-4720}, support = {R35 GM133499/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *JNK Mitogen-Activated Protein Kinases/metabolism ; *MAP Kinase Signaling System ; Phosphorylation ; Mitogen-Activated Protein Kinases/metabolism ; Signal Transduction ; }, abstract = {The classic network of mitogen-activated protein kinases (MAPKs) is highly interconnected and controls a diverse array of biological processes. In multicellular eukaryotes, the MAPKs ERK, JNK, and p38 control opposing cell behaviors but are often activated simultaneously, raising questions about how input-output specificity is achieved. Here, we use multiplexed MAPK activity biosensors to investigate how cell fate control emerges from the connectivity and dynamics of the MAPK network. Through chemical and genetic perturbation, we systematically explore the outputs and functions of all the MAP3 kinases encoded in the human genome and show that MAP3Ks control cell fate by triggering unique combinations of MAPK activity. We show that these MAPK activity combinations explain the paradoxical dual role of JNK signaling as pro-apoptotic or pro-proliferative kinase. Overall, our integrative analysis indicates that the MAPK network operates as a unit to control cell fate and shifts the focus from MAPKs to MAP3Ks to better understand signaling-mediated control of cell fate.}, } @article {pmid36342925, year = {2022}, author = {Oda, AH and Tamura, M and Kaneko, K and Ohta, K and Hatakeyama, TS}, title = {Autotoxin-mediated latecomer killing in yeast communities.}, journal = {PLoS biology}, volume = {20}, number = {11}, pages = {e3001844}, pmid = {36342925}, issn = {1545-7885}, mesh = {Humans ; *Saccharomyces cerevisiae/genetics ; *Yeast, Dried ; Cell Death ; Germ Cells ; Glucose ; }, abstract = {Cellular adaptation to stressful environments such as starvation is essential to the survival of microbial communities, but the uniform response of the cell community may lead to entire cell death or severe damage to their fitness. Here, we demonstrate an elaborate response of the yeast community against glucose depletion, in which the first adapted cells kill the latecomer cells. During glucose depletion, yeast cells release autotoxins, such as leucic acid and L-2keto-3methylvalerate, which can even kill the clonal cells of the ones producing them. Although these autotoxins were likely to induce mass suicide, some cells differentiated to adapt to the autotoxins without genetic changes. If nondifferentiated latecomers tried to invade the habitat, autotoxins damaged or killed the latecomers, but the differentiated cells could selectively survive. Phylogenetically distant fission and budding yeast shared this behavior using the same autotoxins, suggesting that latecomer killing may be the universal system of intercellular communication, which may be relevant to the evolutional transition from unicellular to multicellular organisms.}, } @article {pmid36331628, year = {2022}, author = {Alvarez, FE and Carrillo, JA and Clairambault, J}, title = {Evolution of a structured cell population endowed with plasticity of traits under constraints on and between the traits.}, journal = {Journal of mathematical biology}, volume = {85}, number = {6-7}, pages = {64}, pmid = {36331628}, issn = {1432-1416}, mesh = {Animals ; Phenotype ; Population Dynamics ; *Biological Evolution ; }, abstract = {Confronted with the biological problem of managing plasticity in cell populations, which is in particular responsible for transient and reversible drug resistance in cancer, we propose a rationale consisting of an integro-differential and a reaction-advection-diffusion equation, the properties of which are studied theoretically and numerically. By using a constructive finite volume method, we show the existence and uniqueness of a weak solution and illustrate by numerical approximations and their simulations the capacity of the model to exhibit divergence of traits. This feature may be theoretically interpreted as describing a physiological step towards multicellularity in animal evolution and, closer to present-day clinical challenges in oncology, as a possible representation of bet hedging in cancer cell populations.}, } @article {pmid36329610, year = {2022}, author = {Banijamali, M and Höjer, P and Nagy, A and Hååg, P and Gomero, EP and Stiller, C and Kaminskyy, VO and Ekman, S and Lewensohn, R and Karlström, AE and Viktorsson, K and Ahmadian, A}, title = {Characterizing single extracellular vesicles by droplet barcode sequencing for protein analysis.}, journal = {Journal of extracellular vesicles}, volume = {11}, number = {11}, pages = {e12277}, pmid = {36329610}, issn = {2001-3078}, mesh = {Humans ; *Extracellular Vesicles/genetics ; Biomarkers/metabolism ; Cell Line ; Membrane Proteins/metabolism ; }, abstract = {Small extracellular vesicles (sEVs) have in recent years evolved as a source of biomarkers for disease diagnosis and therapeutic follow up. sEV samples derived from multicellular organisms exhibit a high heterogeneous repertoire of vesicles which current methods based on ensemble measurements cannot capture. In this work we present droplet barcode sequencing for protein analysis (DBS-Pro) to profile surface proteins on individual sEVs, facilitating identification of sEV-subtypes within and between samples. The method allows for analysis of multiple proteins through use of DNA barcoded affinity reagents and sequencing as readout. High throughput single vesicle profiling is enabled through compartmentalization of individual sEVs in emulsion droplets followed by droplet barcoding through PCR. In this proof-of-concept study we demonstrate that DBS-Pro allows for analysis of single sEVs, with a mixing rate below 2%. A total of over 120,000 individual sEVs obtained from a NSCLC cell line and from malignant pleural effusion (MPE) fluid of NSCLC patients have been analyzed based on their surface proteins. We also show that the method enables single vesicle surface protein profiling and by extension characterization of sEV-subtypes, which is essential to identify the cellular origin of vesicles in heterogenous samples.}, } @article {pmid36325178, year = {2022}, author = {Sakai, D and Nishikawa, J and Kakiuchida, H and Hirose, E}, title = {Stack of cellular lamellae forms a silvered cortex to conceal the opaque organ in a transparent gastropod in epipelagic habitat.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e14284}, pmid = {36325178}, issn = {2167-8359}, mesh = {Animals ; Cell Nucleus ; *Gastropoda ; Light ; Vision, Ocular ; }, abstract = {BACKGROUND: Gelatinous zooplankton in epipelagic environments often have highly transparent bodies to avoid detection by their visual predators and prey; however, the digestive systems are often exceptionally opaque even in these organisms. In a holoplanktonic gastropod, Pterotrachea coronata, the visceral nucleus is an opaque organ located at the posterior end of its alimentary system, but this organ has a mirrored surface to conceal its internal opaque tissue.

RESULTS: Our ultrastructural observation proved that the cortex of the visceral nucleus comprised a stack of thin cellular lamellae forming a Bragg reflector, and the thickness of lamellae (0.16 µm in average) and the spaces between the lamellae (0.1 µm in average) tended to become thinner toward inner lamellae. Based on the measured values, we built virtual models of the multilamellar layer comprising 50 lamellae and spaces, and the light reflection on the models was calculated using rigorous coupled wave analysis to evaluate their properties as reflectors. Our simulation supported the idea that the layer is a reflective tissue, and the thickness of the lamella/space must be chirped to reflect sunlight as white/silver light, mostly independent of the angle of incidence.

CONCLUSIONS: In P. coronata, the cortex of the visceral nucleus comprised multicellular lamellae that form a chirped Bragg reflector. It is distinct in structure from the intracellular Bragg structures of common iridophores. This novel Bragg reflector demonstrates the diversity and convergent evolution of reflective tissue using reflectin-like proteins in Mollusca.}, } @article {pmid36316013, year = {2022}, author = {Niklas, KJ and Tiffney, BH}, title = {Viridiplantae Body Plans Viewed Through the Lens of the Fossil Record and Molecular Biology.}, journal = {Integrative and comparative biology}, volume = {}, number = {}, pages = {}, doi = {10.1093/icb/icac150}, pmid = {36316013}, issn = {1557-7023}, abstract = {A review of the fossil record coupled with insights gained from molecular and developmental biology reveal a series of body plan transformations that gave rise to the first land plants. Across diverse algal clades, including the green algae and their descendants, the plant body plan underwent a unicellul ar $\to$ colonial $\to$ simple multicellular $\to \,\,$complex multicellular transformation series. The colonization of land involved increasing body size and associated cell specialization, including cells capable of hydraulic transport. The evolution of the life-cycle that characterizes all known land plant species involved a divergence in body plan phenotypes between the haploid and diploid generations, one adapted to facilitate sexual reproduction (a free-water dependent gametophyte), and another adapted to the dissemination of spores (a more water-independent sporophyte). The amplification of this phenotypic divergence, combined with indeterminate growth in body size, resulted in a desiccation-adapted branched sporophyte with a cuticularized epidermis, stomates, and vascular tissues. Throughout the evolution of the land plants, the body plans of the sporophyte generation involved "axiation," i.e., the acquisition of a cylindrical geometry and subsequent organographic specializations.}, } @article {pmid36313615, year = {2022}, author = {Nicolicht-Amorim, P and Delgado-Garcia, LM and Nakamura, TKE and Courbassier, NR and Mosini, AC and Porcionatto, MA}, title = {Simple and efficient protocol to isolate and culture brain microvascular endothelial cells from newborn mice.}, journal = {Frontiers in cellular neuroscience}, volume = {16}, number = {}, pages = {949412}, pmid = {36313615}, issn = {1662-5102}, abstract = {The neurovascular unit (NVU) is a multicellular structure comprising of neurons, glial cells, and non-neural cells, and it is supported by a specialized extracellular matrix, the basal lamina. Astrocytes, brain microvascular endothelial cells (BMECs), pericytes, and smooth muscle cells constitute the blood-brain barrier (BBB). BMECs have a mesodermal origin and invade the nervous system early in neural tube development, forming the BBB anatomical core. BMECs are connected by adherent junction complexes composed of integral membrane and cytoplasmic proteins. In vivo and in vitro studies have shown that, given the proximity and relationship with neural cells, BMECs acquire a unique gene expression profile, proteome, and specific mechanical and physical properties compared to endothelial cells from the general vasculature. BMECs are fundamental in maintaining brain homeostasis by regulating transcellular and paracellular transport of fluids, molecules, and cells. Therefore, it is essential to gain in-depth knowledge of the dynamic cellular structure of the cells in the NVU and their interactions with health and disease. Here we describe a significantly improved and simplified protocol using C57BL/6 newborn mice at postnatal day 1 (PND1) to isolate, purify, and culture BMECs monolayers in two different substrates (glass coverslips and transwell culture inserts). In vitro characterization and validation of the BMEC primary culture monolayers seeded on glass or insert included light microscopy, immunolabeling, and gene expression profile. Transendothelial electrical resistance (TEER) measurement and diffusion test were used as functional assays for adherent junction complexes and integrity and permeability of BMECs monolayers. The protocol presented here for the isolation and culture of BMECs is more straightforward than previously published protocols and yields a high number of purified cells. Finally, we tested BMECs function using the oxygen-glucose deprivation (OGD) model of hypoxia. This protocol may be suitable as a bioscaffold for secondary cell seeding allowing the study and better understanding of the NVU.}, } @article {pmid36305297, year = {2022}, author = {León-Ruiz, JA and Cruz Ramírez, A}, title = {Predicted landscape of RETINOBLASTOMA-RELATED LxCxE-mediated interactions across the Chloroplastida.}, journal = {The Plant journal : for cell and molecular biology}, volume = {112}, number = {6}, pages = {1507-1524}, doi = {10.1111/tpj.16012}, pmid = {36305297}, issn = {1365-313X}, mesh = {Animals ; *Retinoblastoma ; Retinoblastoma Protein/metabolism ; Cell Differentiation ; *Retinal Neoplasms ; }, abstract = {The colonization of land by a single streptophyte algae lineage some 450 million years ago has been linked to multiple key innovations such as three-dimensional growth, alternation of generations, the presence of stomata, as well as innovations inherent to the birth of major plant lineages, such as the origins of vascular tissues, roots, seeds and flowers. Multicellularity, which evolved multiple times in the Chloroplastida coupled with precise spatiotemporal control of proliferation and differentiation were instrumental for the evolution of these traits. RETINOBLASTOMA-RELATED (RBR), the plant homolog of the metazoan Retinoblastoma protein (pRB), is a highly conserved and multifunctional core cell cycle regulator that has been implicated in the evolution of multicellularity in the green lineage as well as in plant multicellularity-related processes such as proliferation, differentiation, stem cell regulation and asymmetric cell division. RBR fulfills these roles through context-specific protein-protein interactions with proteins containing the Leu-x-Cys-x-Glu (LxCxE) short-linear motif (SLiM); however, how RBR-LxCxE interactions have changed throughout major innovations in the Viridiplantae kingdom is a question that remains unexplored. Here, we employ an in silico evo-devo approach to predict and analyze potential RBR-LxCxE interactions in different representative species of key Chloroplastida lineages, providing a valuable resource for deciphering RBR-LxCxE multiple functions. Furthermore, our analyses suggest that RBR-LxCxE interactions are an important component of RBR functions and that interactions with chromatin modifiers/remodelers, DNA replication and repair machinery are highly conserved throughout the Viridiplantae, while LxCxE interactions with transcriptional regulators likely diversified throughout the water-to-land transition.}, } @article {pmid36283350, year = {2022}, author = {Keller, J and Delaux, PM}, title = {Plant phylogenetics: The never-ending cycle of evolutionary gains and losses.}, journal = {Current biology : CB}, volume = {32}, number = {20}, pages = {R1028-R1029}, doi = {10.1016/j.cub.2022.09.006}, pmid = {36283350}, issn = {1879-0445}, mesh = {*Embryophyta ; Phylogeny ; Plants/genetics ; Evolution, Molecular ; Biological Evolution ; }, abstract = {The Zygnematophyceae is the sister clade to the land plants, but their biology remains mysterious. In a new study, a resolved phylogeny and a scenario for the evolution of multicellularity in that clade are proposed.}, } @article {pmid36264199, year = {2022}, author = {Whye, D and Wood, D and Kim, KH and Chen, C and Makhortova, N and Sahin, M and Buttermore, ED}, title = {Dynamic 3D Combinatorial Generation of hPSC-Derived Neuromesodermal Organoids With Diverse Regional and Cellular Identities.}, journal = {Current protocols}, volume = {2}, number = {10}, pages = {e568}, pmid = {36264199}, issn = {2691-1299}, support = {P50 HD105351/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Pregnancy ; Female ; *Organoids ; Hedgehog Proteins ; Poloxamer ; *Pluripotent Stem Cells ; Fibroblast Growth Factors ; Retinoids ; }, abstract = {Neuromesodermal progenitors represent a unique, bipotent population of progenitors residing in the tail bud of the developing embryo, which give rise to the caudal spinal cord cell types of neuroectodermal lineage as well as the adjacent paraxial somite cell types of mesodermal origin. With the advent of stem cell technologies, including induced pluripotent stem cells (iPSCs), the modeling of rare genetic disorders can be accomplished in vitro to interrogate cell-type specific pathological mechanisms in human patient conditions. Stem cell-derived models of neuromesodermal progenitors have been accomplished by several developmental biology groups; however, most employ a 2D monolayer format that does not fully reflect the complexity of cellular differentiation in the developing embryo. This article presents a dynamic 3D combinatorial method to generate robust populations of human pluripotent stem cell-derived neuromesodermal organoids with multi-cellular fates and regional identities. By utilizing a dynamic 3D suspension format for the differentiation process, the organoids differentiated by following this protocol display a hallmark of embryonic development that involves a morphological elongation known as axial extension. Furthermore, by employing a combinatorial screening assay, we dissect essential pathways for optimally directing the patterning of pluripotent stem cells into neuromesodermal organoids. This protocol highlights the influence of timing, duration, and concentration of WNT and fibroblast growth factor (FGF) signaling pathways on enhancing early neuromesodermal identity, and later, downstream cell fate specification through combined synergies of retinoid signaling and sonic hedgehog activation. Finally, through robust inhibition of the Notch signaling pathway, this protocol accelerates the acquisition of terminal cell identities. This enhanced organoid model can serve as a powerful tool for studying normal developmental processes as well as investigating complex neurodevelopmental disorders, such as neural tube defects. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Robust generation of 3D hPSC-derived spheroid populations in dynamic motion settings Support Protocol 1: Pluronic F-127 reagent preparation and coating to generate low-attachment suspension culture dishes Basic Protocol 2: Enhanced specification of hPSCs into NMP organoids Support Protocol 2: Combinatorial pathway assay for NMP organoid protocol optimization Basic Protocol 3: Differentiation of NMP organoids along diverse cellular trajectories and accelerated terminal fate specification into neurons, neural crest, and sclerotome derivatives.}, } @article {pmid36255595, year = {2022}, author = {Bano, N and Aalam, S and Bag, SK}, title = {Tubby-like proteins (TLPs) transcription factor in different regulatory mechanism in plants: a review.}, journal = {Plant molecular biology}, volume = {110}, number = {6}, pages = {455-468}, pmid = {36255595}, issn = {1573-5028}, mesh = {Animals ; *Transcription Factors/genetics/metabolism ; Amino Acid Sequence ; *Plants/genetics/metabolism ; Stress, Physiological ; Plant Growth Regulators/metabolism ; }, abstract = {Tubby-like proteins (TLPs) transcription factors are found in single-celled to multi-cellular eukaryotes in the form of large multigene families. TLPs are identified through a specific signature of carboxyl terminal tubby domain, required for plasma membrane tethering and amino terminal F-box domain communicate as functional SCF-type E3 ligases. The comprehensive distribution of TLP gene family members in diverse species indicates some conserved functions of TLPs in multicellular organisms. Plant TLPs have higher gene members than animals and these members reported important role in multiple physiological and developmental processes and various environmental stress responses. Although the TLPs are suggested to be a putative transcription factors but their functional mechanism is not much clear. This review provides significant recent updates on TLP-mediated regulation with an insight into its functional roles, origin and evolution and also phytohormones related regulation to combat with various stresses and its involvement in adaptive stress response in crop plants.}, } @article {pmid36252029, year = {2022}, author = {Günther, M and Reimer, C and Herbst, R and Kufs, JE and Rautschek, J and Ueberschaar, N and Zhang, S and Peschel, G and Reimer, L and Regestein, L and Valiante, V and Hillmann, F and Stallforth, P}, title = {Yellow polyketide pigment suppresses premature hatching in social amoeba.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {43}, pages = {e2116122119}, pmid = {36252029}, issn = {1091-6490}, mesh = {*Amoeba/genetics ; *Biological Products/metabolism ; *Dictyostelium/physiology ; Polyketide Synthases/genetics/metabolism ; *Polyketides/metabolism ; }, abstract = {Low-molecular-weight natural products from microbes are indispensable in the development of potent drugs. However, their biological roles within an ecological context often remain elusive. Here, we shed light on natural products from eukaryotic microorganisms that have the ability to transition from single cells to multicellular organisms: the social amoebae. These eukaryotes harbor a large number of polyketide biosynthetic genes in their genomes, yet virtually none of the corresponding products can be isolated or characterized. Using complementary molecular biology approaches, including CRISPR-Cas9, we generated polyketide synthase (pks5) inactivation and overproduction strains of the social amoeba Dictyostelium discoideum. Differential, untargeted metabolomics of wild-type versus mutant fruiting bodies allowed us to pinpoint candidate metabolites derived from the amoebal PKS5. Extrachromosomal expression of the respective gene led to the identification of a yellow polyunsaturated fatty acid. Analysis of the temporospatial production pattern of this compound in conjunction with detailed bioactivity studies revealed the polyketide to be a spore germination suppressor.}, } @article {pmid36250956, year = {2022}, author = {Nedelcu, AM}, title = {Evo-devo perspectives on cancer.}, journal = {Essays in biochemistry}, volume = {66}, number = {6}, pages = {797-815}, doi = {10.1042/EBC20220041}, pmid = {36250956}, issn = {1744-1358}, abstract = {The integration of evolutionary and developmental approaches into the field of evolutionary developmental biology has opened new areas of inquiry- from understanding the evolution of development and its underlying genetic and molecular mechanisms to addressing the role of development in evolution. For the last several decades, the terms 'evolution' and 'development' have been increasingly linked to cancer, in many different frameworks and contexts. This mini-review, as part of a special issue on Evolutionary Developmental Biology, discusses the main areas in cancer research that have been addressed through the lenses of both evolutionary and developmental biology, though not always fully or explicitly integrated in an evo-devo framework. First, it briefly introduces the current views on carcinogenesis that invoke evolutionary and/or developmental perspectives. Then, it discusses the main mechanisms proposed to have specifically evolved to suppress cancer during the evolution of multicellularity. Lastly, it considers whether the evolution of multicellularity and development was shaped by the threat of cancer (a cancer-evo-devo perspective), and/or whether the evolution of developmental programs and life history traits can shape cancer resistance/risk in various lineages (an evo-devo-cancer perspective). A proper evolutionary developmental framework for cancer, both as a disease and in terms of its natural history (in the context of the evolution of multicellularity and development as well as life history traits), could bridge the currently disparate evolutionary and developmental perspectives and uncover aspects that will provide new insights for cancer prevention and treatment.}, } @article {pmid36237424, year = {2022}, author = {Kumar, P and Kumar, P and Mandal, D and Velayutham, R}, title = {The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {985178}, pmid = {36237424}, issn = {2235-2988}, mesh = {Adenosine Triphosphate/metabolism ; Amino Acids/metabolism ; Animals ; Antiparasitic Agents ; Caspases/metabolism ; *Cryptosporidiosis ; *Cryptosporidium ; Deubiquitinating Enzymes/genetics/metabolism ; Humans ; *Parasites/metabolism ; Phylogeny ; Polyubiquitin/genetics/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/metabolism ; Ubiquitination ; }, abstract = {Before the discovery of the proteasome complex, the lysosomes with acidic proteases and caspases in apoptotic pathways were thought to be the only pathways for the degradation of damaged, unfolded, and aged proteins. However, the discovery of 26S and 20S proteasome complexes in eukaryotes and microbes, respectively, established that the degradation of most proteins is a highly regulated ATP-dependent pathway that is significantly conserved across each domain of life. The proteasome is part of the ubiquitin-proteasome system (UPS), where the covalent tagging of a small molecule called ubiquitin (Ub) on the proteins marks its proteasomal degradation. The type and chain length of ubiquitination further determine whether a protein is designated for further roles in multi-cellular processes like DNA repair, trafficking, signal transduction, etc., or whether it will be degraded by the proteasome to recycle the peptides and amino acids. Deubiquitination, on the contrary, is the removal of ubiquitin from its substrate molecule or the conversion of polyubiquitin chains into monoubiquitin as a precursor to ubiquitin. Therefore, deubiquitylating enzymes (DUBs) can maintain the dynamic state of cellular ubiquitination by releasing conjugated ubiquitin from proteins and controlling many cellular pathways that are essential for their survival. Many DUBs are well characterized in the human system with potential drug targets in different cancers. Although, proteasome complex and UPS of parasites, like plasmodium and leishmania, were recently coined as multi-stage drug targets the role of DUBs is completely unexplored even though structural domains and functions of many of these parasite DUBs are conserved having high similarity even with its eukaryotic counterpart. This review summarizes the identification & characterization of different parasite DUBs based on in silico and a few functional studies among different phylogenetic classes of parasites including Metazoan (Schistosoma, Trichinella), Apicomplexan protozoans (Plasmodium, Toxoplasma, Eimeria, Cryptosporidium), Kinetoplastidie (Leishmania, Trypanosoma) and Microsporidia (Nosema). The identification of different homologs of parasite DUBs with structurally similar domains with eukaryotes, and the role of these DUBs alone or in combination with the 20S proteosome complex in regulating the parasite survival/death is further elaborated. We propose that small molecules/inhibitors of human DUBs can be potential antiparasitic agents due to their significant structural conservation.}, } @article {pmid36232785, year = {2022}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Cellular Biogenetic Law and Its Distortion by Protein Interactions: A Possible Unified Framework for Cancer Biology and Regenerative Medicine.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36232785}, issn = {1422-0067}, mesh = {Animals ; Biology ; Cell Differentiation/genetics ; Embryonic Stem Cells ; Humans ; *Induced Pluripotent Stem Cells ; *Neoplasms/genetics/metabolism ; Regenerative Medicine ; }, abstract = {The biogenetic law (recapitulation law) states that ontogenesis recapitulates phylogenesis. However, this law can be distorted by the modification of development. We showed the recapitulation of phylogenesis during the differentiation of various cell types, using a meta-analysis of human single-cell transcriptomes, with the control for cell cycle activity and the improved phylostratigraphy (gene dating). The multipotent progenitors, differentiated from pluripotent embryonic stem cells (ESC), showed the downregulation of unicellular (UC) genes and the upregulation of multicellular (MC) genes, but only in the case of those originating up to the Euteleostomi (bony vertebrates). This picture strikingly resembles the evolutionary profile of regulatory gene expansion due to gene duplication in the human genome. The recapitulation of phylogenesis in the induced pluripotent stem cells (iPSC) during their differentiation resembles the ESC pattern. The unipotent erythroblasts differentiating into erythrocytes showed the downregulation of UC genes and the upregulation of MC genes originating after the Euteleostomi. The MC interactome neighborhood of a protein encoded by a UC gene reverses the gene expression pattern. The functional analysis showed that the evolved environment of the UC proteins is typical for protein modifiers and signaling-related proteins. Besides a fundamental aspect, this approach can provide a unified framework for cancer biology and regenerative/rejuvenation medicine because oncogenesis can be defined as an atavistic reversal to a UC state, while regeneration and rejuvenation require an ontogenetic reversal.}, } @article {pmid36229744, year = {2022}, author = {Akçelik, N and Akçelik, M}, title = {What makes another life possible in bacteria? Global regulators as architects of bacterial biofilms.}, journal = {World journal of microbiology & biotechnology}, volume = {38}, number = {12}, pages = {236}, pmid = {36229744}, issn = {1573-0972}, mesh = {Adenosine Monophosphate/metabolism ; Bacteria/genetics/metabolism ; Bacterial Proteins/metabolism ; Biofilms ; Cyclic GMP/metabolism ; *Ecosystem ; *Gene Expression Regulation, Bacterial ; Guanosine Monophosphate/metabolism ; Plankton/metabolism ; Quorum Sensing/genetics ; }, abstract = {Biofilm structures are the main mode of evolutionary reproductive adaptation of bacteria, and even these features alone, are sufficient to make them the focus of genetic and physiological studies. As this life form is a multicellular-like life form coordinated by genetic and physiological programming, it is quite different from the planktonic form. In bacterial biofilms, which are often composed of more than one species in nature, there is a clear division of labor, nutrient channels, and a language (signaling) established between the cells forming the biofilm. On the other hand, biofilms, especially formed by pathogens, cause important industrial and clinical problems due to their high resistance to environmental stress conditions. Obtaining new data on the molecular basis of bacterial evolution and understanding the intra- and inter-species ecosystem relations in this context, as well as finding permanent solutions to the serious problems they create, are directly related to a detailed understanding of the genetic regulation of bacterial biofilm structures. Today, it is becoming increasingly certain that environmental signals effective in the transition from planktonic form to biofilm form and their receptor/response molecules are generally managed by similar systems and global regulator molecules in bacteria. In this sense; Besides the quorum sensing (QS) systems, cyclic adenosine monophosphate-catabolite suppressor protein (cAMP-CRP) and bis-(3'-5') cyclic dimeric guanosine monophosphate (c-di-GMP) signaling molecules are of critical importance. In this review article, current information on bacterial biofilms is summarized and interpreted based on this framework.}, } @article {pmid36218381, year = {2022}, author = {Silva, VSD and Machado, CR}, title = {Sex in protists: A new perspective on the reproduction mechanisms of trypanosomatids.}, journal = {Genetics and molecular biology}, volume = {45}, number = {3}, pages = {e20220065}, pmid = {36218381}, issn = {1415-4757}, abstract = {The Protist kingdom individuals are the most ancestral representatives of eukaryotes. They have inhabited Earth since ancient times and are currently found in the most diverse environments presenting a great heterogeneity of life forms. The unicellular and multicellular algae, photosynthetic and heterotrophic organisms, as well as free-living and pathogenic protozoa represents the protist group. The evolution of sex is directly associated with the origin of eukaryotes being protists the earliest protagonists of sexual reproduction on earth. In eukaryotes, the recombination through genetic exchange is a ubiquitous mechanism that can be stimulated by DNA damage. Scientific evidences support the hypothesis that reactive oxygen species (ROS) induced DNA damage can promote sexual recombination in eukaryotes which might have been a decisive factor for the origin of sex. The fact that some recombination enzymes also participate in meiotic sex in modern eukaryotes reinforces the idea that sexual reproduction emerged as consequence of specific mechanisms to cope with mutations and alterations in genetic material. In this review we will discuss about origin of sex and different strategies of evolve sexual reproduction in some protists such that cause human diseases like malaria, toxoplasmosis, sleeping sickness, Chagas disease, and leishmaniasis.}, } @article {pmid36217823, year = {2022}, author = {Datta, S and Ratcliff, WC}, title = {Illuminating a new path to multicellularity.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36217823}, issn = {2050-084X}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; }, abstract = {A new species of multicellular bacteria broadens our understanding of prokaryotic multicellularity and provides insight into how multicellular organisms arise.}, } @article {pmid36217817, year = {2022}, author = {Mizuno, K and Maree, M and Nagamura, T and Koga, A and Hirayama, S and Furukawa, S and Tanaka, K and Morikawa, K}, title = {Novel multicellular prokaryote discovered next to an underground stream.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36217817}, issn = {2050-084X}, mesh = {*Biological Evolution ; *Groundwater ; Pralidoxime Compounds ; Water ; }, abstract = {A diversity of prokaryotes currently exhibit multicellularity with different generation mechanisms in a variety of contexts of ecology on Earth. In the present study, we report a new type of multicellular bacterium, HS-3, isolated from an underground stream. HS-3 self-organizes its filamentous cells into a layer-structured colony with the properties of a nematic liquid crystal. After maturation, the colony starts to form a semi-closed sphere accommodating clusters of coccobacillus daughter cells and selectively releases them upon contact with water. This is the first report that shows that a liquid-crystal status of cells can support the prokaryotic multicellular behavior. Importantly, the observed behavior of HS-3 suggests that the recurrent intermittent exposure of colonies to water flow in the cave might have been the ecological context that cultivated the evolutionary transition from unicellular to multicellular life. This is the new extant model that underpins theories regarding a role of ecological context in the emergence of multicellularity.}, } @article {pmid36213345, year = {2022}, author = {Ren, P and Dong, X and Vijg, J}, title = {Age-related somatic mutation burden in human tissues.}, journal = {Frontiers in aging}, volume = {3}, number = {}, pages = {1018119}, pmid = {36213345}, issn = {2673-6217}, support = {P01 AG017242/AG/NIA NIH HHS/United States ; }, abstract = {The genome of multicellular organisms carries the hereditary information necessary for the development of all organs and tissues and to maintain function in adulthood. To ensure the genetic stability of the species, genomes are protected against changes in sequence information. However, genomes are not static. De novo mutations in germline cells are passed on to offspring and generate the variation needed in evolution. Moreover, postzygotic mutations occur in all somatic cells during development and aging. These somatic mutations remain limited to the individual, generating tissues that are genome mosaics. Insight into such mutations and their consequences has been limited due to their extremely low abundance, with most mutations unique for each cell. Recent advances in sequencing, including whole genome sequencing at the single-cell level, have now led to the first insights into somatic mutation burdens in human tissues. Here, we will first briefly describe the latest methodology for somatic mutation analysis, then review our current knowledge of somatic mutation burden in human tissues and, finally, briefly discuss the possible functional impact of somatic mutations on the aging process and age-related diseases, including cancer and diseases other than cancer.}, } @article {pmid36202151, year = {2022}, author = {Wang, P and Chen, C and Wang, Q and Chen, H and Chen, C and Xu, J and Wang, X and Song, T}, title = {Tumor inhibition via magneto-mechanical oscillation by magnetotactic bacteria under a swing MF.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {351}, number = {}, pages = {941-953}, doi = {10.1016/j.jconrel.2022.09.059}, pmid = {36202151}, issn = {1873-4995}, mesh = {Animals ; *Magnetosomes/metabolism ; Gram-Negative Bacteria ; Bacteria/metabolism ; Magnetics ; Mammals ; }, abstract = {Since magnetic micro/nano-materials can serve as multifunctional transducers for remote control of cell functions by applying diverse magnetic fields, magnetic cell manipulation provides a highly promising tool in biomedical research encompassing neuromodulation, tissue regeneration engineering and tumor cell destruction. Magnetotactic bacteria (MTB), which contain natural magnetic materials, can sensitively respond to external magnetic fields via their endogenous magnetosome chains. Here, we developed a technique for magnetotactic bacteria-based cell modulation and tumor suppression combined with a swing magnetic field. We enabled MTB cells to recognize and bind to mammalian tumor cells via functional modification with RGD peptides onto the surfaces of MTB cells, and RGD-modified MTB bacteria could interact with the targeted tumor cells effectively. The magnetic torque, which was due to the interaction of the long magnetosome chain inside the MTB bacterial cell and the applied swing magnetic field, could result in obvious swing magnetic behaviors of the modified MTB bacteria bound to tumor cell surfaces and thus subsequently exert a sustained magnetomechanical oscillation on the tumor cell surfaces, which could induce a significant activation of Ca[2+] ion influx in vitro and tumor growth inhibition in vivo. These findings suggest that MTB cells mediated magnetomechanical stimulation, which is remotely controlled by dynamic magnetic fields, as an effective way to regulate cell signaling and treat tumor growth, which will shed the light on further biomedical applications utilizing whole magnetotactic bacteria.}, } @article {pmid36199687, year = {2022}, author = {Fuloria, NK and Raheja, RK and Shah, KH and Oza, MJ and Kulkarni, YA and Subramaniyan, V and Sekar, M and Fuloria, S}, title = {Biological activities of meroterpenoids isolated from different sources.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {830103}, pmid = {36199687}, issn = {1663-9812}, abstract = {Meroterpenoids are natural products synthesized by unicellular organisms such as bacteria and multicellular organisms such as fungi, plants, and animals, including those of marine origin. Structurally, these compounds exhibit a wide diversity depending upon the origin and the biosynthetic pathway they emerge from. This diversity in structural features imparts a wide spectrum of biological activity to meroterpenoids. Based on the biosynthetic pathway of origin, these compounds are either polyketide-terpenoids or non-polyketide terpenoids. The recent surge of interest in meroterpenoids has led to a systematic screening of these compounds for many biological actions. Different meroterpenoids have been recorded for a broad range of operations, such as anti-cholinesterase, COX-2 inhibitory, anti-leishmanial, anti-diabetic, anti-oxidative, anti-inflammatory, anti-neoplastic, anti-bacterial, antimalarial, anti-viral, anti-obesity, and insecticidal activity. Meroterpenoids also possess inhibitory activity against the expression of nitric oxide, TNF- α, and other inflammatory mediators. These compounds also show renal protective, cardioprotective, and neuroprotective activities. The present review includes literature from 1999 to date and discusses 590 biologically active meroterpenoids, of which 231 are from fungal sources, 212 are from various species of plants, and 147 are from marine sources such as algae and sponges.}, } @article {pmid36198374, year = {2022}, author = {Grunt, TW and Valent, P}, title = {Cancer - A devastating disease, but also an eye-opener and window into the deep mysteries of life and its origins.}, journal = {Progress in biophysics and molecular biology}, volume = {175}, number = {}, pages = {131-139}, doi = {10.1016/j.pbiomolbio.2022.09.009}, pmid = {36198374}, issn = {1873-1732}, mesh = {Humans ; *Biological Evolution ; Thermodynamics ; Entropy ; *Neoplasms ; Mutation ; }, abstract = {Although cancer is still the second leading cause of death worldwide, basic research has largely elucidated the underlying mechanisms that lead us deep into the laws of animate and inanimate nature. This review aims to demonstrate that the cancer process profoundly affects and reprograms fundamental principles and concepts of cellular life by harnessing the natural mechanisms of biological evolution. It is shown that mutation and selection - the drivers of cancer formation and progression - are mandatory consequences of Boltzmann's version of the second law of thermodynamics, which stipulates that entropy (or disorder) according to probability never decreases, followed by Darwinian evolution by filtering for the suitable geno- and karyotypes. Cancer research has shown that malignant cells can develop gradually or abruptly depending on the prevailing stress conditions. Similar principles were then observed in the evolution of species, referred to as micro- and macroevolution. Cancer cells can be related to phylogenetically older forms of life, and malignant transformation can be viewed as reverse (atavistic) evolution, accompanied by typical rearrangement of system information and loss of 'social' behavior. It becomes obvious that in nature no distinction is made between normal biology and pathobiology. Instead, everything follows the rules of natural evolution. This illustrates the depth of the cancer problem and may explain the serious difficulties faced in trying to eradicate cancer.}, } @article {pmid36196535, year = {2022}, author = {Gauthier, AE and Rotjan, RD and Kagan, JC}, title = {Lipopolysaccharide detection by the innate immune system may be an uncommon defence strategy used in nature.}, journal = {Open biology}, volume = {12}, number = {10}, pages = {220146}, pmid = {36196535}, issn = {2046-2441}, mesh = {Animals ; Immune System/metabolism ; Immunity, Innate ; *Lipopolysaccharides ; Mammals ; *Pathogen-Associated Molecular Pattern Molecules ; }, abstract = {Since the publication of the Janeway's Pattern Recognition hypothesis in 1989, study of pathogen-associated molecular patterns (PAMPs) and their immuno-stimulatory activities has accelerated. Most studies in this area have been conducted in model organisms, which leaves many open questions about the universality of PAMP biology across living systems. Mammals have evolved multiple proteins that operate as receptors for the PAMP lipopolysaccharide (LPS) from Gram-negative bacteria, but LPS is not immuno-stimulatory in all eukaryotes. In this review, we examine the history of LPS as a PAMP in mammals, recent data on LPS structure and its ability to activate mammalian innate immune receptors, and how these activities compare across commonly studied eukaryotes. We discuss why LPS may have evolved to be immuno-stimulatory in some eukaryotes but not others and propose two hypotheses about the evolution of PAMP structure based on the ecology and environmental context of the organism in question. Understanding PAMP structures and stimulatory mechanisms across multi-cellular life will provide insights into the evolutionary origins of innate immunity and may lead to the discovery of new PAMP variations of scientific and therapeutic interest.}, } @article {pmid36180988, year = {2022}, author = {Turishcheva, E and Vildanova, M and Onishchenko, G and Smirnova, E}, title = {The Role of Endoplasmic Reticulum Stress in Differentiation of Cells of Mesenchymal Origin.}, journal = {Biochemistry. Biokhimiia}, volume = {87}, number = {9}, pages = {916-931}, pmid = {36180988}, issn = {1608-3040}, mesh = {*COVID-19 ; Cell Differentiation ; *Endoplasmic Reticulum Stress ; Fibrosis ; Humans ; Unfolded Protein Response ; }, abstract = {Endoplasmic reticulum (ER) is a multifunctional membrane-enclosed organelle. One of the major ER functions is cotranslational transport and processing of secretory, lysosomal, and transmembrane proteins. Impaired protein processing caused by disturbances in the ER homeostasis results in the ER stress. Restoration of normal ER functioning requires activation of an adaptive mechanism involving cell response to misfolded proteins, the so-called unfolded protein response (UPR). Besides controlling protein folding, UPR plays a key role in other physiological processes, in particular, differentiation of cells of connective, muscle, epithelial, and neural tissues. Cell differentiation is induced by the physiological levels of ER stress, while excessive ER stress suppresses differentiation and can result in cell death. So far, it remains unknown whether UPR activation induces cell differentiation or if UPR is initiated by the upregulated synthesis of secretory proteins during cell differentiation. Cell differentiation is an important stage in the development of multicellular organisms and is tightly controlled. Suppression or excessive activation of this process can lead to the development of various pathologies in an organism. In particular, impairments in the differentiation of connective tissue cells can result in the development of fibrosis, obesity, and osteoporosis. Recently, special attention has been paid to fibrosis as one of the major complications of COVID-19. Therefore, studying the role of UPR in the activation of cell differentiation is of both theoretical and practical interest, as it might result in the identification of molecular targets for selective regulation of cell differentiation stages and as well as the potential to modulate the mechanisms involved in the development of various pathological states.}, } @article {pmid36179980, year = {2023}, author = {Hiraki, HL and Matera, DL and Wang, WY and Prabhu, ES and Zhang, Z and Midekssa, F and Argento, AE and Buschhaus, JM and Humphries, BA and Luker, GD and Pena-Francesch, A and Baker, BM}, title = {Fiber density and matrix stiffness modulate distinct cell migration modes in a 3D stroma mimetic composite hydrogel.}, journal = {Acta biomaterialia}, volume = {163}, number = {}, pages = {378-391}, pmid = {36179980}, issn = {1878-7568}, support = {R01 EB030474/EB/NIBIB NIH HHS/United States ; T32 DE007057/DE/NIDCR NIH HHS/United States ; }, mesh = {Humans ; *Hydrogels/pharmacology/chemistry ; Cell Movement ; *Neoplasms ; Biocompatible Materials/pharmacology ; Epithelial Cells ; Extracellular Matrix ; Tumor Microenvironment ; }, abstract = {The peritumoral stroma is a complex 3D tissue that provides cells with myriad biophysical and biochemical cues. Histologic observations suggest that during metastatic spread of carcinomas, these cues influence transformed epithelial cells, prompting a diversity of migration modes spanning single cell and multicellular phenotypes. Purported consequences of these variations in tumor escape strategies include differential metastatic capability and therapy resistance. Therefore, understanding how cues from the peritumoral stromal microenvironment regulate migration mode has both prognostic and therapeutic value. Here, we utilize a synthetic stromal mimetic in which matrix fiber density and bulk hydrogel mechanics can be orthogonally tuned to investigate the contribution of these two key matrix attributes on MCF10A migration mode phenotypes, epithelial-mesenchymal transition (EMT), and invasive potential. We develop an automated computational image analysis framework to extract migratory phenotypes from fluorescent images and determine 3D migration metrics relevant to metastatic spread. Using this analysis, we find that matrix fiber density and bulk hydrogel mechanics distinctly contribute to a variety of MCF10A migration modes including amoeboid, single mesenchymal, clusters, and strands. We identify combinations of physical and soluble cues that induce a variety of migration modes originating from the same MCF10A spheroid and use these settings to examine a functional consequence of migration mode -resistance to apoptosis. We find that cells migrating as strands are more resistant to staurosporine-induced apoptosis than either disconnected clusters or individual invading cells. Improved models of the peritumoral stromal microenvironment and understanding of the relationships between matrix attributes and cell migration mode can aid ongoing efforts to identify effective cancer therapeutics that address cell plasticity-based therapy resistances. STATEMENT OF SIGNIFICANCE: Stromal extracellular matrix structure dictates both cell homeostasis and activation towards migratory phenotypes. However decoupling the effects of myriad biophysical cues has been difficult to achieve. Here, we encapsulate electrospun fiber segments within an amorphous hydrogel to create a fiber-reinforced hydrogel composite in which fiber density and hydrogel stiffness can be orthogonally tuned. Quantification of 3D cell migration reveal these two parameters uniquely contribute to a diversity of migration phenotypes spanning amoeboid, single mesenchymal, multicellular cluster, and collective strand. By tuning biophysical and biochemical cues to elicit heterogeneous migration phenotypes, we find that collective strands best resist apoptosis. This work establishes a composite approach to modulate fibrous topography and bulk hydrogel mechanics and identified biomaterial parameters to direct distinct 3D cell migration phenotypes.}, } @article {pmid36178156, year = {2022}, author = {Liau, P and Kim, C and Saxton, MA and Malkin, SY}, title = {Microbial succession in a marine sediment: Inferring interspecific microbial interactions with marine cable bacteria.}, journal = {Environmental microbiology}, volume = {24}, number = {12}, pages = {6348-6364}, pmid = {36178156}, issn = {1462-2920}, mesh = {RNA, Ribosomal, 16S/genetics ; Oxidation-Reduction ; Geologic Sediments/microbiology ; *Deltaproteobacteria/genetics ; Bacteria/genetics ; Sulfur ; *Gammaproteobacteria/genetics ; *Microbiota ; Microbial Interactions ; Phylogeny ; }, abstract = {Cable bacteria are long, filamentous, multicellular bacteria that grow in marine sediments and couple sulfide oxidation to oxygen reduction over centimetre-scale distances via long-distance electron transport. Cable bacteria can strongly modify biogeochemical cycling and may affect microbial community networks. Here we examine interspecific interactions with marine cable bacteria (Ca. Electrothrix) by monitoring the succession of 16S rRNA amplicons (DNA and RNA) and cell abundance across depth and time, contrasting sediments with and without cable bacteria growth. In the oxic zone, cable bacteria activity was positively associated with abundant predatory bacteria (Bdellovibrionota, Myxococcota, Bradymonadales), indicating putative predation on cathodic cells. At suboxic depths, cable bacteria activity was positively associated with sulfate-reducing and magnetotactic bacteria, consistent with cable bacteria functioning as ecosystem engineers that modify their local biogeochemical environment, benefitting certain microbes. Cable bacteria activity was negatively associated with chemoautotrophic sulfur-oxidizing Gammaproteobacteria (Thiogranum, Sedimenticola) at oxic depths, suggesting competition, and positively correlated with these taxa at suboxic depths, suggesting syntrophy and/or facilitation. These observations are consistent with chemoautotrophic sulfur oxidizers benefitting from an oxidizing potential imparted by cable bacteria at suboxic depths, possibly by using cable bacteria as acceptors for electrons or electron equivalents, but by an as yet enigmatic mechanism.}, } @article {pmid36147948, year = {2022}, author = {Boutry, J and Tissot, S and Mekaoui, N and Dujon, A and Meliani, J and Hamede, R and Ujvari, B and Roche, B and Nedelcu, AM and Tokolyi, J and Thomas, F}, title = {Tumors alter life history traits in the freshwater cnidarian, Hydra oligactis.}, journal = {iScience}, volume = {25}, number = {10}, pages = {105034}, pmid = {36147948}, issn = {2589-0042}, abstract = {Although tumors can occur during the lifetime of most multicellular organisms and have the potential to influence health, how they alter life-history traits in tumor-bearing individuals remains poorly documented. This question was explored using the freshwater cnidarian Hydra oligactis, a species sometimes affected by vertically transmitted tumors. We found that tumorous polyps have a reduced survival compared to healthy ones. However, they also displayed higher asexual reproductive effort, by producing more often multiple buds than healthy ones. A similar acceleration is observed for the sexual reproduction (estimated through gamete production). Because tumoral cells are not transmitted through this reproductive mode, this finding suggests that hosts may adaptively respond to tumors, compensating the expected fitness losses by increasing their immediate reproductive effort. This study supports the hypothesis that tumorigenesis has the potential to influence the biology, ecology, and evolution of multicellular species, and thus should be considered more by evolutionary ecologists.}, } @article {pmid36138796, year = {2022}, author = {Gecow, A and Iantovics, LB and Tez, M}, title = {Cancer and Chaos and the Complex Network Model of a Multicellular Organism.}, journal = {Biology}, volume = {11}, number = {9}, pages = {}, pmid = {36138796}, issn = {2079-7737}, abstract = {In the search of theoretical models describing cancer, one of promising directions is chaos. It is connected to ideas of "genome chaos" and "life on the edge of chaos", but they profoundly differ in the meaning of the term "chaos". To build any coherent models, notions used by both ideas should be firstly brought closer. The hypothesis "life on the edge of chaos" using deterministic chaos has been radically deepened developed in recent years by the discovery of half-chaos. This new view requires a deeper interpretation within the range of the cell and the organism. It has impacts on understanding "chaos" in the term "genome chaos". This study intends to present such an interpretation on the basis of which such searches will be easier and closer to intuition. We interpret genome chaos as deterministic chaos in a large module of half-chaotic network modeling the cell. We observed such chaotic modules in simulations of evolution controlled by weaker variant of natural selection. We also discuss differences between free and somatic cells in modeling their disturbance using half-chaotic networks.}, } @article {pmid36135738, year = {2022}, author = {Guryanova, SV and Ovchinnikova, TV}, title = {Innate Immunity Mechanisms in Marine Multicellular Organisms.}, journal = {Marine drugs}, volume = {20}, number = {9}, pages = {}, pmid = {36135738}, issn = {1660-3397}, support = {22-14-00380//Russian Science Foundation/ ; }, mesh = {*Immunity, Innate ; Receptors, Pattern Recognition/metabolism ; *Signal Transduction ; }, abstract = {The innate immune system provides an adequate response to stress factors and pathogens through pattern recognition receptors (PRRs), located on the surface of cell membranes and in the cytoplasm. Generally, the structures of PRRs are formed by several domains that are evolutionarily conserved, with a fairly high degree of homology in representatives of different species. The orthologs of TLRs, NLRs, RLRs and CLRs are widely represented, not only in marine chordates, but also in invertebrates. Study of the interactions of the most ancient marine multicellular organisms with microorganisms gives us an idea of the evolution of molecular mechanisms of protection against pathogens and reveals new functions of already known proteins in ensuring the body's homeostasis. The review discusses innate immunity mechanisms of protection of marine invertebrate organisms against infections, using the examples of ancient multicellular hydroids, tunicates, echinoderms, and marine worms in the context of searching for analogies with vertebrate innate immunity. Due to the fact that mucous membranes first arose in marine invertebrates that have existed for several hundred million years, study of their innate immune system is both of fundamental importance in terms of understanding molecular mechanisms of host defense, and of practical application, including the search of new antimicrobial agents for subsequent use in medicine, veterinary and biotechnology.}, } @article {pmid36134999, year = {2022}, author = {Ma, C and Liu, K and Li, Q and Xiong, Y and Xu, C and Zhang, W and Ruan, C and Li, X and Lei, X}, title = {Synthetic Extracellular Matrices for 3D Culture of Schwann Cells, Hepatocytes, and HUVECs.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {9}, number = {9}, pages = {}, pmid = {36134999}, issn = {2306-5354}, support = {2021YFA0719303//National Key Research and Development Program of China/ ; 81901058, 81900686//National Natural Science Foundation of China/ ; 2022A1515010952//Natural Science Foundation of Guangdong Province/ ; JCYJ20210324115814040//Shenzhen Fundamental Research Foundation/ ; }, abstract = {Synthetic hydrogels from polyisocyanides (PIC) are a type of novel thermoreversible biomaterials, which can covalently bind biomolecules such as adhesion peptides to provide a suitable extracellular matrix (ECM)-like microenvironment for different cells. Although we have demonstrated that PIC is suitable for three-dimensional (3D) culture of several cell types, it is unknown whether this hydrogel sustains the proliferation and passaging of cells originating from different germ layers. In the present study, we propose a 3D culture system for three representative cell sources: Schwann cells (ectoderm), hepatocytes (endoderm), and endothelial cells (mesoderm). Both Schwann cells and hepatocytes proliferated into multicellular spheroids and maintained their properties, regardless of the amount of cell-adhesive RGD motifs in long-term culture. Notably, Schwann cells grew into larger spheroids in RGD-free PIC than in PIC-RGD, while HL-7702 showed the opposite behavior. Endothelial cells (human umbilical vein endothelial cells, HUVECs) spread and formed an endothelial cell (EC) network only in PIC-RGD. Moreover, in a hepatocyte/HUVEC co-culture system, the characteristics of both cells were well kept for a long period in PIC-RGD. In all, our work highlights a simple ECM mimic that supports the growth and phenotype maintenance of cells from all germ layers in the long term. Our findings might contribute to research on biological development, organoid engineering, and in vitro drug screening.}, } @article {pmid36127898, year = {2022}, author = {Bargel, H and Trossmann, VT and Sommer, C and Scheibel, T}, title = {Bioselectivity of silk protein-based materials and their bio-inspired applications.}, journal = {Beilstein journal of nanotechnology}, volume = {13}, number = {}, pages = {902-921}, pmid = {36127898}, issn = {2190-4286}, abstract = {Adhesion to material surfaces is crucial for almost all organisms regarding subsequent biological responses. Mammalian cell attachment to a surrounding biological matrix is essential for maintaining their survival and function concerning tissue formation. Conversely, the adhesion and presence of microbes interferes with important multicellular processes of tissue development. Therefore, tailoring bioselective, biologically active, and multifunctional materials for biomedical applications is a modern focus of biomaterial research. Engineering biomaterials that stimulate and interact with cell receptors to support binding and subsequent physiological responses of multicellular systems attracted much interest in the last years. Further to this, the increasing threat of multidrug resistance of pathogens against antibiotics to human health urgently requires new material concepts for preventing microbial infestation and biofilm formation. Thus, materials exhibiting microbial repellence or antimicrobial behaviour to reduce inflammation, while selectively enhancing regeneration in host tissues are of utmost interest. In this context, protein-based materials are interesting candidates due to their natural origin, biological activity, and structural properties. Silk materials, in particular those made of spider silk proteins and their recombinant counterparts, are characterized by extraordinary properties including excellent biocompatibility, slow biodegradation, low immunogenicity, and non-toxicity, making them ideally suited for tissue engineering and biomedical applications. Furthermore, recombinant production technologies allow for application-specific modification to develop adjustable, bioactive materials. The present review focusses on biological processes and surface interactions involved in the bioselective adhesion of mammalian cells and repellence of microbes on protein-based material surfaces. In addition, it highlights the importance of materials made of recombinant spider silk proteins, focussing on the progress regarding bioselectivity.}, } @article {pmid36127662, year = {2022}, author = {Chai, S and Aria, C and Hua, H}, title = {A stem group Codium alga from the latest Ediacaran of South China provides taxonomic insight into the early diversification of the plant kingdom.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {199}, pmid = {36127662}, issn = {1741-7007}, mesh = {Animals ; China ; *Chlorophyta/genetics ; *Ecosystem ; Eukaryotic Cells ; Fossils ; }, abstract = {BACKGROUND: In recent years, Precambrian lifeforms have generated an ever-increasing interest because they revealed a rich eukaryotic diversity prior to the Cambrian explosion of modern animals. Among them, macroalgae are known to be a conspicuous component of Neoproterozoic ecosystems, and chlorophytes in particular are already documented in the Tonian, when they were so far expected to originate. However, like for other major eukaryotic lineages, and despite predictions of molecular clock analyses placing roots of these lineages well into the Neoproterozoic, a taxonomic constraint on Precambrian green algae has remained difficult.

RESULTS: Here, we present an exceptionally preserved spherical, coenocytic unicellular alga from the latest Ediacaran Dengying Formation of South China (> ca. 541 Ma), known from both external and internal morphology, fully tridimensional and in great detail. Tomographic X-ray and electronic microscopy revealed a characteristic medulla made of intertwined siphons and tightly packed peripheral utricles, suggesting these fossils belong to the Bryopsidales genus Codium. However, its distinctly smaller size compared to extant species leads us to create Protocodium sinense gen. et sp. nov. and a phylomorphospace investigation points to a possible stem group affinity.

CONCLUSIONS: Our finding has several important implications. First, Protocodium allows for a more precise calibration of Archaeplastida and directly confirms that a group as derived as Ulvophyceae was already well diversified in various ecosystems prior to the Cambrian explosion. Details of tridimensional morphology also invite a reassessment of the identification of other Ediacaran algae, such as Chuaria, to better discriminate mono-versus multicellularity, and suggest unicellular Codium-like morphotypes could be much older and widespread. More broadly, Protocodium provides insights into the early diversification of the plant kingdom, the composition of Precambrian ecosystems, and the extreme longevity of certain eukaryotic plans of organization.}, } @article {pmid36114258, year = {2022}, author = {La Fortezza, M and Rendueles, O and Keller, H and Velicer, GJ}, title = {Hidden paths to endless forms most wonderful: ecology latently shapes evolution of multicellular development in predatory bacteria.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {977}, pmid = {36114258}, issn = {2399-3642}, mesh = {Agar ; Animals ; *Myxococcus xanthus/genetics ; Phenotype ; *Predatory Behavior ; }, abstract = {Ecological causes of developmental evolution, for example from predation, remain much investigated, but the potential importance of latent phenotypes in eco-evo-devo has received little attention. Using the predatory bacterium Myxococcus xanthus, which undergoes aggregative fruiting body development upon starvation, we tested whether adaptation to distinct growth environments that do not induce development latently alters developmental phenotypes under starvation conditions that do induce development. In an evolution experiment named MyxoEE-3, growing M. xanthus populations swarmed across agar surfaces while adapting to conditions varying at factors such as surface stiffness or prey identity. Such ecological variation during growth was found to greatly impact the latent evolution of development, including fruiting body morphology, the degree of morphological trait correlation, reaction norms, degrees of developmental plasticity and stochastic diversification. For example, some prey environments promoted retention of developmental proficiency whereas others led to its systematic loss. Our results have implications for understanding evolutionary interactions among predation, development and motility in myxobacterial life cycles, and, more broadly, how ecology can profoundly shape the evolution of developmental systems latently rather than by direct selection on developmental features.}, } @article {pmid36105707, year = {2022}, author = {Huang, X and Yi, P and Liu, Y and Li, Q and Jiang, Y and Yi, Y and Yan, H}, title = {RrTTG1 promotes fruit prickle development through an MBW complex in Rosa roxburghii.}, journal = {Frontiers in plant science}, volume = {13}, number = {}, pages = {939270}, pmid = {36105707}, issn = {1664-462X}, abstract = {Fruit prickles are widely distributed on the pericarp and exhibit polymorphic traits at different developmental stages. Although they are multicellular appendages that are well-known for helping plants defend against biotic and abiotic stresses, their origination and molecular mechanism are still less known. Here, we studied the origination and molecular mechanism of fruit prickles in Rosa roxburghii. Using morphological and histological observations, we found that the fruit prickle primordium of R. roxburghii originated from the ground meristem that underwent cell division to form flagelliform prickles, continued to enlarge, and finally lignified to form mature fruit prickles. We amplified a homolog of candidate gene TRANSPARENT TESTA GLABRA1 (TTG1) from R. roxburghii, named RrTTG1. RrTTG1 harbored four conserved WD-repeat domains and was exclusively nuclear-localized. Using qRT-PCR and in situ hybridization, we found that RrTTG1 was constitutively expressed and highly expressed during the initiation and cell expansion phases of fruit prickles. Ectopic expression analysis in Arabidopsis proved that RrTTG1 substantially enhanced the number of trichome and pigmentation production and inhibited root hair formation. Besides, RrTTG1 complemented the phenotypes of the ttg1 mutant in Arabidopsis, thus indicating that RrTTG1 played pleiotropic roles akin to AtTTG1. We demonstrated that the RrTTG1 only interacted with RrEGL3, a homolog of ENHANCER OF GLABRA3 (EGL3), via yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. Briefly, RrTTG1 might positively regulate the initiation of fruit prickle primordium and cell enlargement by forming the RrTTG1-RrEGL3-RrGL1 complex in R. roxburghii. Therefore, our results help characterize the RrTTG1 in R. roxburghii and also elucidate the establishment of the prickles regulatory system in the Rosaceae plants.}, } @article {pmid36105585, year = {2022}, author = {Adiba, S and Forget, M and De Monte, S}, title = {Evolving social behavior through selection of single-cell adhesion in Dictyostelium discoideum.}, journal = {iScience}, volume = {25}, number = {9}, pages = {105006}, pmid = {36105585}, issn = {2589-0042}, abstract = {The social amoeba Dictyostelium discoideum commonly forms chimeric fruiting bodies. Genetic variants that produce a higher proportion of spores are predicted to undercut multicellular organization unless cooperators assort positively. Cell adhesion is considered a primary factor driving such assortment, but evolution of adhesion has not been experimentally connected to changes in social performance. We modified by experimental evolution the efficiency of individual cells in attaching to a surface. Surprisingly, evolution appears to have produced social cooperators irrespective of whether stronger or weaker adhesion was selected. Quantification of reproductive success, cell-cell adhesion, and developmental patterns, however, revealed two distinct social behaviors, as captured when the classical metric for social success is generalized by considering clonal spore production. Our work shows that cell mechanical interactions can constrain the evolution of development and sociality in chimeras and that elucidation of proximate mechanisms is necessary to understand the ultimate emergence of multicellular organization.}, } @article {pmid36103852, year = {2022}, author = {Zaman, R and Epelman, S}, title = {Resident cardiac macrophages: Heterogeneity and function in health and disease.}, journal = {Immunity}, volume = {55}, number = {9}, pages = {1549-1563}, doi = {10.1016/j.immuni.2022.08.009}, pmid = {36103852}, issn = {1097-4180}, mesh = {*Heart/physiology ; *Macrophages ; Myocardium ; }, abstract = {Understanding tissue macrophage biology has become challenging in recent years due the ever-increasing complexity in macrophage-subset identification and functional characterization. This is particularly important within the myocardium, as we have come to understand that macrophages play multifaceted roles in cardiac health and disease, and heart disease remains the leading cause of death worldwide. Here, we review recent progress in the field, focusing on resident cardiac macrophage heterogeneity, origins, and functions at steady state and after injury. We stratify resident cardiac macrophage functions by the ability of macrophages to either directly influence cardiac physiology or indirectly influence cardiac physiology through orchestrating multi-cellular communication with cardiomyocytes and stromal and immune populations.}, } @article {pmid36102042, year = {2022}, author = {Xie, Q and Xiong, C and Yang, Q and Zheng, F and Larkin, RM and Zhang, J and Wang, T and Zhang, Y and Ouyang, B and Lu, Y and Ye, J and Ye, Z and Yang, C}, title = {A novel regulatory complex mediated by Lanata (Ln) controls multicellular trichome formation in tomato.}, journal = {The New phytologist}, volume = {236}, number = {6}, pages = {2294-2310}, doi = {10.1111/nph.18492}, pmid = {36102042}, issn = {1469-8137}, mesh = {*Trichomes/metabolism ; *Solanum lycopersicum/genetics/metabolism ; Gene Expression Regulation, Plant ; Plant Proteins/genetics/metabolism ; Plant Epidermis/metabolism ; }, abstract = {Trichomes that originate from plant aerial epidermis act as mechanical and chemical barriers against herbivores. Although several regulators have recently been identified, the regulatory pathway underlying multicellular trichome formation remains largely unknown in tomato. Here, we report a novel HD-ZIP IV transcription factor, Lanata (Ln), a missense mutation which caused the hairy phenotype. Biochemical analyses demonstrate that Ln separately interacts with two trichome regulators, Woolly (Wo) and Hair (H). Genetic and molecular evidence demonstrates that Ln directly regulates the expression of H. The interaction between Ln and Wo can increase trichome density by enhancing the expression of SlCycB2 and SlCycB3, which we previously showed are involved in tomato trichome formation. Furthermore, SlCycB2 represses the transactivation of the SlCycB3 gene by Ln and vice versa. Our findings provide new insights into the novel regulatory network controlling multicellular trichome formation in tomato.}, } @article {pmid36099169, year = {2022}, author = {Ress, V and Traulsen, A and Pichugin, Y}, title = {Eco-evolutionary dynamics of clonal multicellular life cycles.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36099169}, issn = {2050-084X}, mesh = {Animals ; *Biological Evolution ; *Life Cycle Stages ; Models, Theoretical ; }, abstract = {The evolution of multicellular life cycles is a central process in the course of the emergence of multicellularity. The simplest multicellular life cycle is comprised of the growth of the propagule into a colony and its fragmentation to give rise to new propagules. The majority of theoretical models assume selection among life cycles to be driven by internal properties of multicellular groups, resulting in growth competition. At the same time, the influence of interactions between groups on the evolution of life cycles is rarely even considered. Here, we present a model of colonial life cycle evolution taking into account group interactions. Our work shows that the outcome of evolution could be coexistence between multiple life cycles or that the outcome may depend on the initial state of the population - scenarios impossible without group interactions. At the same time, we found that some results of these simpler models remain relevant: evolutionary stable strategies in our model are restricted to binary fragmentation - the same class of life cycles that contains all evolutionarily optimal life cycles in the model without interactions. Our results demonstrate that while models neglecting interactions can capture short-term dynamics, they fall short in predicting the population-scale picture of evolution.}, } @article {pmid36098425, year = {2022}, author = {Noh, S and Capodanno, BJ and Xu, S and Hamilton, MC and Strassmann, JE and Queller, DC}, title = {Reduced and Nonreduced Genomes in Paraburkholderia Symbionts of Social Amoebas.}, journal = {mSystems}, volume = {7}, number = {5}, pages = {e0056222}, pmid = {36098425}, issn = {2379-5077}, support = {P20 GM103423/GM/NIGMS NIH HHS/United States ; P20GM103423//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Animals ; *Amoeba/microbiology ; *Dictyostelium/genetics ; Eukaryota ; *Burkholderiaceae/genetics ; Bacteria/genetics ; Soil ; }, abstract = {The social amoeba Dictyostelium discoideum is a predatory soil protist frequently used for studying host-pathogen interactions. A subset of D. discoideum strains isolated from soil persistently carry symbiotic Paraburkholderia, recently formally described as P. agricolaris, P. bonniea, and P. hayleyella. The three facultative symbiont species of D. discoideum present a unique opportunity to study a naturally occurring symbiosis in a laboratory model protist. There is a large difference in genome size between P. agricolaris (8.7 million base pairs [Mbp]) versus P. hayleyella and P. bonniea (4.1 Mbp). We took a comparative genomics approach and compared the three genomes of D. discoideum symbionts to 12 additional Paraburkholderia genomes to test for genome evolution patterns that frequently accompany host adaptation. Overall, P. agricolaris is difficult to distinguish from other Paraburkholderia based on its genome size and content, but the reduced genomes of P. bonniea and P. hayleyella display characteristics indicative of genome streamlining rather than deterioration during adaptation to their protist hosts. In addition, D. discoideum-symbiont genomes have increased secretion system and motility genes that may mediate interactions with their host. Specifically, adjacent BurBor-like type 3 and T6SS-5-like type 6 secretion system operons shared among all three D. discoideum-symbiont genomes may be important for host interaction. Horizontal transfer of these secretion system operons within the amoeba host environment may have contributed to the unique ability of these symbionts to establish and maintain a symbiotic relationship with D. discoideum. IMPORTANCE Protists are a diverse group of typically single cell eukaryotes. Bacteria and archaea that form long-term symbiotic relationships with protists may evolve in additional ways than those in relationships with multicellular eukaryotes such as plants, animals, or fungi. Social amoebas are a predatory soil protist sometimes found with symbiotic bacteria living inside their cells. They present a unique opportunity to explore a naturally occurring symbiosis in a protist frequently used for studying host-pathogen interactions. We show that one amoeba-symbiont species is similar to other related bacteria in genome size and content, while the two reduced-genome-symbiont species show characteristics of genome streamlining rather than deterioration during adaptation to their host. We also identify sets of genes present in all three amoeba-symbiont genomes that are potentially used for host-symbiont interactions. Because the amoeba symbionts are distantly related, the amoeba host environment may be where these genes were shared among symbionts.}, } @article {pmid36077628, year = {2022}, author = {Nam, C and Ziman, B and Sheth, M and Zhao, H and Lin, DC}, title = {Genomic and Epigenomic Characterization of Tumor Organoid Models.}, journal = {Cancers}, volume = {14}, number = {17}, pages = {}, pmid = {36077628}, issn = {2072-6694}, support = {R37 CA237022/CA/NCI NIH HHS/United States ; P30CA014089/CA/NCI NIH HHS/United States ; R37CA237022/NH/NIH HHS/United States ; }, abstract = {Tumor organoid modeling has been recognized as a state-of-the-art system for in vitro research on cancer biology and precision oncology. Organoid culture technologies offer distinctive advantages, including faithful maintenance of physiological and pathological characteristics of human disease, self-organization into three-dimensional multicellular structures, and preservation of genomic and epigenomic landscapes of the originating tumor. These features effectively position organoid modeling between traditional cell line cultures in two dimensions and in vivo animal models as a valid, versatile, and robust system for cancer research. Here, we review recent advances in genomic and epigenomic characterization of tumor organoids and the novel findings obtained, highlight significant progressions achieved in organoid modeling of gene-drug interactions and genotype-phenotype associations, and offer perspectives on future opportunities for organoid modeling in basic and clinical cancer research.}, } @article {pmid36077092, year = {2022}, author = {Anatskaya, OV and Vinogradov, AE}, title = {Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring.}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, pmid = {36077092}, issn = {1422-0067}, support = {Agreement No. 075-15-2021-1075, signed 28 September 2021//Ministry of Science and Higher Education of the Russian Federation/ ; }, mesh = {Chromatin ; Epigenesis, Genetic ; *Gene Regulatory Networks ; Humans ; *Polyploidy ; Proto-Oncogenes ; }, abstract = {Polyploid cells demonstrate biological plasticity and stress adaptation in evolution; development; and pathologies, including cardiovascular diseases, neurodegeneration, and cancer. The nature of ploidy-related advantages is still not completely understood. Here, we summarize the literature on molecular mechanisms underlying ploidy-related adaptive features. Polyploidy can regulate gene expression via chromatin opening, reawakening ancient evolutionary programs of embryonality. Chromatin opening switches on genes with bivalent chromatin domains that promote adaptation via rapid induction in response to signals of stress or morphogenesis. Therefore, stress-associated polyploidy can activate Myc proto-oncogenes, which further promote chromatin opening. Moreover, Myc proto-oncogenes can trigger polyploidization de novo and accelerate genome accumulation in already polyploid cells. As a result of these cooperative effects, polyploidy can increase the ability of cells to search for adaptive states of cellular programs through gene regulatory network rewiring. This ability is manifested in epigenetic plasticity associated with traits of stemness, unicellularity, flexible energy metabolism, and a complex system of DNA damage protection, combining primitive error-prone unicellular repair pathways, advanced error-free multicellular repair pathways, and DNA damage-buffering ability. These three features can be considered important components of the increased adaptability of polyploid cells. The evidence presented here contribute to the understanding of the nature of stress resistance associated with ploidy and may be useful in the development of new methods for the prevention and treatment of cardiovascular and oncological diseases.}, } @article {pmid36076976, year = {2022}, author = {Burzacka-Hinz, A and Narajczyk, M and Dudek, M and Szlachetko, DL}, title = {Micromorphology of Labellum in Selected Dendrobium Sw. (Orchidaceae, Dendrobieae).}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, pmid = {36076976}, issn = {1422-0067}, mesh = {*Dendrobium ; Flowers/anatomy & histology ; Microscopy, Electron, Scanning ; *Orchidaceae/anatomy & histology ; Phylogeny ; Trichomes ; }, abstract = {Dendrobium is one of the most species-rich genera of the Paleotropical orchids. It embraces more than 1000 species, most of which are epiphytes. The strong variation in floral characters causes many identification difficulties within this genus. One of the key structures, often sufficient in identification on a species level, is the labellum, which in many species of Dendrobium possesses a thickened callus and various types of trichomes and papillae. The aim of this study is to identify and describe the structures present on the labellum surface of the analyzed species, determine their distribution and density, as well as to check whether the obtained data have taxonomic value. In this paper, we present the results of a micromorphological study on the labellum of 21 species of Dendrobium, representing 13 sections, using scanning electron microscopy (SEM). Our studies revealed the presence of both uni- and multicellular structures on the surface of the labellum. We observed three types of trichomes (conical, cylindrical, ellipsoidal) and three types of papillae (conical, cylindrical, semicircular). Neither trichomes nor papillae were recorded for five species. In addition, we made diagrams showing the distribution and density of structures on the labellum. Based on the micromorphological results combined with the phylogenetic tree performed, we suggest that the presence/absence of labellum structures does not necessarily reflect the phylogenetic relationship and might be misleading, as in some cases, they arise due to convergence.}, } @article {pmid36064151, year = {2022}, author = {Smiley, P and Levin, M}, title = {Competition for finite resources as coordination mechanism for morphogenesis: An evolutionary algorithm study of digital embryogeny.}, journal = {Bio Systems}, volume = {221}, number = {}, pages = {104762}, doi = {10.1016/j.biosystems.2022.104762}, pmid = {36064151}, issn = {1872-8324}, mesh = {Algorithms ; *Biological Evolution ; Computer Simulation ; *Embryonic Development/genetics ; Morphogenesis/genetics ; }, abstract = {The standard view of embryogenesis is one of cooperation driven by the cells' shared genetics and evolutionary interests. However, numerous examples from developmental biology and agriculture reveal a surprising amount of competition among body cells, tissues, and organs for both metabolic and informational resources. To explain the existence of such competition we had hypothesized that evolution uses limiting "reservoirs" of resource molecules as a communication medium - a global scratchpad, to enable tissues across the body to coordinate growth. Here, we test this hypothesis via an evolutionary simulation of embryogeny in silico. Genomes encode state transition rules for cells, such as proliferation, differentiation, and resource use, enabling virtual embryos to develop a specific large-scale morphology. An evolutionary algorithm operates over the genomes, with fitness defined as a function of specific morphological requirements for the final embryo shape. We found that not only does such an algorithm rapidly discover rules for cellular behavior that reliably make embryos with specific anatomical properties, but that it discovers the strategy of using finite resources to coordinate development. Given the option of using finite or infinite reservoirs (which determine cells' ability to carry out specific actions), evolution preferentially uses finite reservoirs, which results in higher fitness and increased consistency (without needing direct selection for morphological invariance). We report aspects of anatomical, physiological/transcriptional, and genomic analysis of evolved virtual embryos that help understand how evolution can use competition among genetically identical subunits within a multicellular body to coordinate reliable, complex morphogenesis. Our results suggest that under some conditions, composite multi-scale systems will promote conflict and artificial scarcity for their components.}, } @article {pmid36055238, year = {2022}, author = {Hess, S and Williams, SK and Busch, A and Irisarri, I and Delwiche, CF and de Vries, S and Darienko, T and Roger, AJ and Archibald, JM and Buschmann, H and von Schwartzenberg, K and de Vries, J}, title = {A phylogenomically informed five-order system for the closest relatives of land plants.}, journal = {Current biology : CB}, volume = {32}, number = {20}, pages = {4473-4482.e7}, pmid = {36055238}, issn = {1879-0445}, mesh = {Phylogeny ; Biological Evolution ; *Embryophyta/genetics ; *Charophyceae/genetics ; *Streptophyta ; Plants ; Soil ; }, abstract = {The evolution of streptophytes had a profound impact on life on Earth. They brought forth those photosynthetic eukaryotes that today dominate the macroscopic flora: the land plants (Embryophyta).[1] There is convincing evidence that the unicellular/filamentous Zygnematophyceae-and not the morphologically more elaborate Coleochaetophyceae or Charophyceae-are the closest algal relatives of land plants.[2-6] Despite the species richness (>4,000), wide distribution, and key evolutionary position of the zygnematophytes, their internal phylogeny remains largely unresolved.[7,8] There are also putative zygnematophytes with interesting body plan modifications (e.g., filamentous growth) whose phylogenetic affiliations remain unknown. Here, we studied a filamentous green alga (strain MZCH580) from an Austrian peat bog with central or parietal chloroplasts that lack discernible pyrenoids. It represents Mougeotiopsis calospora PALLA, an enigmatic alga that was described more than 120 years ago[9] but never subjected to molecular analyses. We generated transcriptomic data of M. calospora strain MZCH580 and conducted comprehensive phylogenomic analyses (326 nuclear loci) for 46 taxonomically diverse zygnematophytes. Strain MZCH580 falls in a deep-branching zygnematophycean clade together with some unicellular species and thus represents a formerly unknown zygnematophycean lineage with filamentous growth. Our well-supported phylogenomic tree lets us propose a new five-order system for the Zygnematophyceae and provides evidence for at least five independent origins of true filamentous growth in the closest algal relatives of land plants. This phylogeny provides a robust and comprehensive framework for performing comparative analyses and inferring the evolution of cellular traits and body plans in the closest relatives of land plants.}, } @article {pmid36045216, year = {2022}, author = {Michla, M and Wilhelm, C}, title = {Food for thought - ILC metabolism in the context of helminth infections.}, journal = {Mucosal immunology}, volume = {15}, number = {6}, pages = {1234-1242}, pmid = {36045216}, issn = {1935-3456}, mesh = {Animals ; Humans ; Immunity, Innate ; Lymphocytes ; *Helminthiasis ; *Helminths ; Inflammation ; }, abstract = {Helminths are multicellular ancient organisms residing as parasites at mucosal surfaces of their host. Through adaptation and co-evolution with their hosts, helminths have been able to develop tolerance mechanisms to limit inflammation and avoid expulsion. The study of helminth infections as an integral part of tissue immunology allowed us to understand fundamental aspects of mucosal and barrier immunology, which led to the discovery of a new group of tissue-resident immune cells, innate lymphoid cells (ILC), over a decade ago. Here, we review the intricate interplay between helminth infections and type 2 ILC (ILC2) biology, discuss the host metabolic adaptation to helminth infections and the metabolic pathways fueling ILC2 responses. We hypothesize that nutrient competition between host and helminths may have prevented chronic inflammation in the past and argue that a detailed understanding of the metabolic restraints imposed by helminth infections may offer new therapeutic avenues in the future.}, } @article {pmid36043790, year = {2022}, author = {Kuroda, K and Yamamoto, K and Nakai, R and Hirakata, Y and Kubota, K and Nobu, MK and Narihiro, T}, title = {Symbiosis between Candidatus Patescibacteria and Archaea Discovered in Wastewater-Treating Bioreactors.}, journal = {mBio}, volume = {13}, number = {5}, pages = {e0171122}, pmid = {36043790}, issn = {2150-7511}, mesh = {*Archaea/metabolism ; Symbiosis/genetics ; Wastewater ; Phylogeny ; In Situ Hybridization, Fluorescence ; Sewage ; Bacteria/genetics ; *Euryarchaeota ; Bioreactors ; Protein Sorting Signals/genetics ; }, abstract = {Each prokaryotic domain, Bacteria and Archaea, contains a large and diverse group of organisms characterized by their ultrasmall cell size and symbiotic lifestyles (potentially commensal, mutualistic, and parasitic relationships), namely, Candidatus Patescibacteria (also known as the Candidate Phyla Radiation/CPR superphylum) and DPANN archaea, respectively. Cultivation-based approaches have revealed that Ca. Patescibacteria and DPANN symbiotically interact with bacterial and archaeal partners and hosts, respectively, but that cross-domain symbiosis and parasitism have never been observed. By amending wastewater treatment sludge samples with methanogenic archaea, we observed increased abundances of Ca. Patescibacteria (Ca. Yanofskybacteria/UBA5738) and, using fluorescence in situ hybridization (FISH), discovered that nearly all of the Ca. Yanofskybacteria/UBA5738 cells were attached to Methanothrix (95.7 ± 2.1%) and that none of the cells were attached to other lineages, implying high host dependency and specificity. Methanothrix filaments (multicellular) with Ca. Yanofskybacteria/UBA5738 attached had significantly more cells with no or low detectable ribosomal activity (based on FISH fluorescence) and often showed deformations at the sites of attachment (based on transmission electron microscopy), suggesting that the interaction is parasitic. Metagenome-assisted metabolic reconstruction showed that Ca. Yanofskybacteria/UBA5738 lacks most of the biosynthetic pathways necessary for cell growth and universally conserves three unique gene arrays that contain multiple genes with signal peptides in the metagenome-assembled genomes of the Ca. Yanofskybacteria/UBA5738 lineage. The results shed light on a novel cross-domain symbiosis and inspire potential strategies for culturing CPR and DPANN. IMPORTANCE One highly diverse phylogenetic group of Bacteria, Ca. Patescibacteria, remains poorly understood, but, from the few cultured representatives and metagenomic investigations, they are thought to live symbiotically or parasitically with other bacteria or even with eukarya. We explored the possibility of symbiotic interactions with Archaea by amending wastewater treatment sludge samples that were rich in Ca. Patescibacteria and Archaea with an isolate archaeon that is closely related to a methanogen population abundant in situ (Methanothrix). This strategic cultivation successfully established enrichment cultures that were mainly comprised of Ca. Patescibacteria (family level lineage Ca. Yanofskybacteria/UBA5738) and Methanothrix, in which we found highly specific physical interactions between the two organisms. Microscopic observations based on transmission electron microscopy, target-specific fluorescence in situ hybridization, and metagenomic analyses showed evidence that the interaction is likely parasitic. The results show a novel cross-domain parasitism between Bacteria and Archaea and suggest that the amendment of host Archaea may be an effective approach in culturing novel Ca. Patescibacteria.}, } @article {pmid36036016, year = {2022}, author = {Fujiwara, M and Akiyama-Oda, Y and Oda, H}, title = {Virtual spherical-shaped multicellular platform for simulating the morphogenetic processes of spider-like body axis formation.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {932814}, pmid = {36036016}, issn = {2296-634X}, abstract = {Remodeling of multicellular architecture is a critical developmental process for shaping the axis of a bilaterally symmetric animal body and involves coordinated cell-cell interactions and cell rearrangement. In arthropods, the early embryonic process that leads to the segmented body axis varies at the cellular and molecular levels depending on the species. Developmental studies using insect and spider model species have provided specific examples of these diversified mechanisms that regulate axis formation and segmentation in arthropod embryos. However, there are few theoretical models for how diversity in the early embryonic process occurred during evolution, in part because of a limited computational infrastructure. We developed a virtual spherical-shaped multicellular platform to reproduce body axis-forming processes. Each virtual cell behaves according to the cell vertex model, with the computational program organized in a hierarchical order from cells and tissues to whole embryos. Using an initial set of two different mechanical states for cell differentiation and global directional signals that are linked to the planar polarity of each cell, the virtual cell assembly exhibited morphogenetic processes similar to those observed in spider embryos. We found that the development of an elongating body axis is achieved through implementation of an interactive cell polarity parameter associated with edge tension at the cell-cell adhesion interface, with no local control of the cell division rate and direction. We also showed that modifying the settings can cause variation in morphogenetic processes. This platform also can embed a gene network that generates waves of gene expression in a virtual dynamic multicellular field. This study provides a computational platform for testing the development and evolution of animal body patterns.}, } @article {pmid36028058, year = {2022}, author = {Senthilkumar, I and Howley, E and McEvoy, E}, title = {Thermodynamically-motivated chemo-mechanical models and multicellular simulation to provide new insight into active cell and tumour remodelling.}, journal = {Experimental cell research}, volume = {419}, number = {2}, pages = {113317}, doi = {10.1016/j.yexcr.2022.113317}, pmid = {36028058}, issn = {1090-2422}, mesh = {Computer Simulation ; Humans ; *Models, Biological ; *Neoplasms ; Tumor Microenvironment ; }, abstract = {Computational models can shape our understanding of cell and tissue remodelling, from cell spreading, to active force generation, adhesion, and growth. In this mini-review, we discuss recent progress in modelling of chemo-mechanical cell behaviour and the evolution of multicellular systems. In particular, we highlight recent advances in (i) free-energy based single cell models that can provide new fundamental insight into cell spreading, cancer cell invasion, stem cell differentiation, and remodelling in disease, and (ii) mechanical agent-based models to simulate large numbers of discrete interacting cells in proliferative tumours. We describe how new biological understanding has emerged from such theoretical models, and the trade-offs and constraints associated with current approaches. Ultimately, we aim to make a case for why theory should be integrated with an experimental workflow to optimise new in-vitro studies, to predict feedback between cells and their microenvironment, and to deepen understanding of active cell behaviour.}, } @article {pmid36013944, year = {2022}, author = {Guryanova, SV}, title = {Regulation of Immune Homeostasis via Muramyl Peptides-Low Molecular Weight Bioregulators of Bacterial Origin.}, journal = {Microorganisms}, volume = {10}, number = {8}, pages = {}, pmid = {36013944}, issn = {2076-2607}, abstract = {Metabolites and fragments of bacterial cells play an important role in the formation of immune homeostasis. Formed in the course of evolution, symbiotic relationships between microorganisms and a macroorganism are manifested, in particular, in the regulation of numerous physiological functions of the human body by the innate immunity receptors. Low molecular weight bioregulators of bacterial origin have recently attracted more and more attention as drugs in the prevention and composition of complex therapy for a wide range of diseases of bacterial and viral etiology. Signaling networks show cascades of causal relationships of deterministic phenomena that support the homeostasis of multicellular organisms at different levels. To create networks, data from numerous biomedical and clinical research databases were used to prepare expert systems for use in pharmacological and biomedical research with an emphasis on muramyl dipeptides. Muramyl peptides are the fragments of the cell wall of Gram-positive and Gram-negative bacteria. Binding of muramyl peptides with intracellular NOD2 receptors is crucial for an immune response on pathogens. Depending on the microenvironment and duration of action, muramyl peptides possess positive or negative regulation of inflammation. Other factors, such as genetic, pollutions, method of application and stress also contribute and should be taken into account. A system biology approach should be used in order to systemize all experimental data for rigorous analysis, with the aim of understanding intrinsic pathways of homeostasis, in order to define precise medicine therapy and drug design.}, } @article {pmid36011312, year = {2022}, author = {Le, NG and van Ulsen, P and van Spanning, R and Brouwer, A and van Straalen, NM and Roelofs, D}, title = {A Functional Carbohydrate Degrading Enzyme Potentially Acquired by Horizontal Gene Transfer in the Genome of the Soil Invertebrate Folsomia candida.}, journal = {Genes}, volume = {13}, number = {8}, pages = {}, pmid = {36011312}, issn = {2073-4425}, mesh = {Animals ; *Arthropods/genetics ; Bacteria/genetics ; Carbohydrates ; Escherichia coli/genetics ; Eukaryota ; *Gene Transfer, Horizontal ; Insecta ; Protein Sorting Signals/genetics ; Soil ; }, abstract = {Horizontal gene transfer (HGT) is defined as the acquisition by an organism of hereditary material from a phylogenetically unrelated organism. This process is mostly observed among bacteria and archaea, and considered less likely between microbes and multicellular eukaryotes. However, recent studies provide compelling evidence of the evolutionary importance of HGT in eukaryotes, driving functional innovation. Here, we study an HGT event in Folsomia candida (Collembola, Hexapoda) of a carbohydrate-active enzyme homologous to glycosyl hydrase group 43 (GH43). The gene encodes an N-terminal signal peptide, targeting the product for excretion, which suggests that it contributes to the diversity of digestive capacities of the detritivore host. The predicted α-L-arabinofuranosidase shows high similarity to genes in two other Collembola, an insect and a tardigrade. The gene was cloned and expressed in Escherichia coli using a cell-free protein expression system. The expressed protein showed activity against p-nitrophenyl-α-L-arabinofuranoside. Our work provides evidence for functional activity of an HGT gene in a soil-living detritivore, most likely from a bacterial donor, with genuine eukaryotic properties, such as a signal peptide. Co-evolution of metazoan GH43 genes with the Panarthropoda phylogeny suggests the HGT event took place early in the evolution of this ecdysozoan lineage.}, } @article {pmid36002568, year = {2022}, author = {Ocaña-Pallarès, E and Williams, TA and López-Escardó, D and Arroyo, AS and Pathmanathan, JS and Bapteste, E and Tikhonenkov, DV and Keeling, PJ and Szöllősi, GJ and Ruiz-Trillo, I}, title = {Divergent genomic trajectories predate the origin of animals and fungi.}, journal = {Nature}, volume = {609}, number = {7928}, pages = {747-753}, pmid = {36002568}, issn = {1476-4687}, support = {616960/ERC_/European Research Council/International ; 714774/ERC_/European Research Council/International ; 615274/ERC_/European Research Council/International ; }, mesh = {Animals ; *Evolution, Molecular ; *Fungi/genetics ; Gene Transfer, Horizontal ; Genes ; *Genome/genetics ; Genome, Fungal/genetics ; *Genomics ; Metabolism/genetics ; *Phylogeny ; }, abstract = {Animals and fungi have radically distinct morphologies, yet both evolved within the same eukaryotic supergroup: Opisthokonta[1,2]. Here we reconstructed the trajectory of genetic changes that accompanied the origin of Metazoa and Fungi since the divergence of Opisthokonta with a dataset that includes four novel genomes from crucial positions in the Opisthokonta phylogeny. We show that animals arose only after the accumulation of genes functionally important for their multicellularity, a tendency that began in the pre-metazoan ancestors and later accelerated in the metazoan root. By contrast, the pre-fungal ancestors experienced net losses of most functional categories, including those gained in the path to Metazoa. On a broad-scale functional level, fungal genomes contain a higher proportion of metabolic genes and diverged less from the last common ancestor of Opisthokonta than did the gene repertoires of Metazoa. Metazoa and Fungi also show differences regarding gene gain mechanisms. Gene fusions are more prevalent in Metazoa, whereas a larger fraction of gene gains were detected as horizontal gene transfers in Fungi and protists, in agreement with the long-standing idea that transfers would be less relevant in Metazoa due to germline isolation[3-5]. Together, our results indicate that animals and fungi evolved under two contrasting trajectories of genetic change that predated the origin of both groups. The gradual establishment of two clearly differentiated genomic contexts thus set the stage for the emergence of Metazoa and Fungi.}, } @article {pmid36002411, year = {2022}, author = {Shi, B and Huang, X and Fu, X and Wang, B}, title = {[Advances in the plant multicellular network analysis].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {38}, number = {8}, pages = {2798-2810}, doi = {10.13345/j.cjb.220127}, pmid = {36002411}, issn = {1872-2075}, mesh = {*Plants ; }, abstract = {Multicellular network analysis is a method for topological properties analysis of cells. The functions of organs are determined by their inner cells. The arrangement of cells within organs endows higher-order functionality through a structure-function relationship, though the organizational properties of these multicellular configurations remain poorly understood. Multicellular network analysis with multicellular models established by 3D scanning of plants, will further discover the plant development mechanism, and provide clues for synthesizing plant multicellular systems. In this paper, we review the development of multicellular models, summarize the process of multicellular network analysis, and describe the development and application of multicellular network analysis in plants. In addition, this review also provides perspective on future development of plant multicellular network analysis.}, } @article {pmid35999597, year = {2022}, author = {Gahan, JM and Leclère, L and Hernandez-Valladares, M and Rentzsch, F}, title = {A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {184}, pmid = {35999597}, issn = {1741-7007}, mesh = {Animals ; Cell Differentiation ; *Chromatin ; Histone Demethylases/genetics ; Mammals/genetics ; Phylogeny ; *Sea Anemones/metabolism ; }, abstract = {BACKGROUND: Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Most chromatin modifiers, however, predate the evolution of animal multicellularity, and how they gained new functions and became integrated into the regulatory networks underlying development is unclear. One way this may occur is the evolution of new scaffolding proteins that integrate multiple chromatin regulators into larger complexes that facilitate coordinated deposition or removal of different chromatin modifications. We test this hypothesis by analyzing the evolution of the CoREST-Lsd1-HDAC complex.

RESULTS: Using phylogenetic analyses, we show that a bona fide CoREST homolog is found only in choanoflagellates and animals. We then use the sea anemone Nematostella vectensis as a model for early branching metazoans and identify a conserved CoREST complex by immunoprecipitation and mass spectrometry of an endogenously tagged Lsd1 allele. In addition to CoREST, Lsd1 and HDAC1/2 this complex contains homologs of HMG20A/B and PHF21A, two subunits that have previously only been identified in mammalian CoREST complexes. NvCoREST expression overlaps fully with that of NvLsd1 throughout development, with higher levels in differentiated neural cells. NvCoREST mutants, generated using CRISPR-Cas9, fail to develop beyond the primary polyp stage, thereby revealing essential roles during development and for the differentiation of cnidocytes that phenocopy NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach.

CONCLUSIONS: The identification of a Nematostella CoREST-Lsd1-HDAC1/2 complex, its similarity in composition with the vertebrate complex, and the near-identical expression patterns and mutant phenotypes of NvCoREST and NvLsd1 suggest that the complex was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit.}, } @article {pmid35995772, year = {2022}, author = {Nyongesa, S and Weber, PM and Bernet, È and Pulido, F and Nieves, C and Nieckarz, M and Delaby, M and Viehboeck, T and Krause, N and Rivera-Millot, A and Nakamura, A and Vischer, NOE and vanNieuwenhze, M and Brun, YV and Cava, F and Bulgheresi, S and Veyrier, FJ}, title = {Evolution of longitudinal division in multicellular bacteria of the Neisseriaceae family.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {4853}, pmid = {35995772}, issn = {2041-1723}, mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; Biological Evolution ; *Cell Division ; Cell Wall/metabolism ; Mammals/microbiology ; *Neisseriaceae/cytology ; Peptidoglycan/metabolism ; }, abstract = {Rod-shaped bacteria typically elongate and divide by transverse fission. However, several bacterial species can form rod-shaped cells that divide longitudinally. Here, we study the evolution of cell shape and division mode within the family Neisseriaceae, which includes Gram-negative coccoid and rod-shaped species. In particular, bacteria of the genera Alysiella, Simonsiella and Conchiformibius, which can be found in the oral cavity of mammals, are multicellular and divide longitudinally. We use comparative genomics and ultrastructural microscopy to infer that longitudinal division within Neisseriaceae evolved from a rod-shaped ancestor. In multicellular longitudinally-dividing species, neighbouring cells within multicellular filaments are attached by their lateral peptidoglycan. In these bacteria, peptidoglycan insertion does not appear concentric, i.e. from the cell periphery to its centre, but as a medial sheet guillotining each cell. Finally, we identify genes and alleles associated with multicellularity and longitudinal division, including the acquisition of amidase-encoding gene amiC2, and amino acid changes in proteins including MreB and FtsA. Introduction of amiC2 and allelic substitution of mreB in a rod-shaped species that divides by transverse fission results in shorter cells with longer septa. Our work sheds light on the evolution of multicellularity and longitudinal division in bacteria, and suggests that members of the Neisseriaceae family may be good models to study these processes due to their morphological plasticity and genetic tractability.}, } @article {pmid35988806, year = {2022}, author = {Salminen, A}, title = {Mutual antagonism between aryl hydrocarbon receptor and hypoxia-inducible factor-1α (AhR/HIF-1α) signaling: Impact on the aging process.}, journal = {Cellular signalling}, volume = {99}, number = {}, pages = {110445}, doi = {10.1016/j.cellsig.2022.110445}, pmid = {35988806}, issn = {1873-3913}, mesh = {DNA ; *Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Oxygen ; Prolyl Hydroxylases ; Pyridinolcarbamate ; *Receptors, Aryl Hydrocarbon/genetics/metabolism ; Tryptophan ; }, abstract = {The ambient oxygen level, many environmental toxins, and the rays of ultraviolet light (UV) provide a significant risk for the maintenance of organismal homeostasis. The aryl hydrocarbon receptors (AhR) represent a complex sensor system not only for environmental toxins and UV radiation but also for many endogenous ligands, e.g., L-tryptophan metabolites. The AhR signaling system is evolutionarily conserved and AhR homologs existed as many as 600 million years ago. The ancient atmosphere demanded the evolution of an oxygen-sensing system, i.e., hypoxia-inducible transcription factors (HIF) and their prolyl hydroxylase regulators (PHD). Given that both signaling systems have important roles in embryogenesis, it seems that they have been involved in the evolution of multicellular organisms. The evolutionary origin of the aging process is unknown although it is most likely associated with the evolution of multicellularity. Intriguingly, there is compelling evidence that while HIF-1α signaling extends the lifespan, that of AhR promotes many age-related degenerative processes, e.g., it increases oxidative stress, inhibits autophagy, promotes cellular senescence, and aggravates extracellular matrix degeneration. In contrast, HIF-1α signaling stimulates autophagy, inhibits cellular senescence, and enhances cell proliferation. Interestingly, there is a clear antagonism between the AhR and HIF-1α signaling pathways. For instance, (i) AhR and HIF-1α factors heterodimerize with the same factor, ARNT/HIF-1β, leading to their competition for DNA-binding, (ii) AhR and HIF-1α signaling exert antagonistic effects on autophagy, and (iii) co-chaperone p23 exhibits specific functions in the signaling of AhR and HIF-1α factors. One might speculate that it is the competition between the AhR and HIF-1α signaling pathways that is a driving force in the aging process.}, } @article {pmid35975712, year = {2022}, author = {Bourrat, P and Doulcier, G and Rose, CJ and Rainey, PB and Hammerschmidt, K}, title = {Tradeoff breaking as a model of evolutionary transitions in individuality and limits of the fitness-decoupling metaphor.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35975712}, issn = {2050-084X}, mesh = {*Biological Evolution ; *Metaphor ; Phenotype ; Selection, Genetic ; }, abstract = {Evolutionary transitions in individuality (ETIs) involve the formation of Darwinian collectives from Darwinian particles. The transition from cells to multicellular life is a prime example. During an ETI, collectives become units of selection in their own right. However, the underlying processes are poorly understood. One observation used to identify the completion of an ETI is an increase in collective-level performance accompanied by a decrease in particle-level performance, for example measured by growth rate. This seemingly counterintuitive dynamic has been referred to as fitness decoupling and has been used to interpret both models and experimental data. Extending and unifying results from the literature, we show that fitness of particles and collectives can never decouple because calculations of fitness performed over appropriate and equivalent time intervals are necessarily the same provided the population reaches a stable collective size distribution. By way of solution, we draw attention to the value of mechanistic approaches that emphasise traits, and tradeoffs among traits, as opposed to fitness. This trait-based approach is sufficient to capture dynamics that underpin evolutionary transitions. In addition, drawing upon both experimental and theoretical studies, we show that while early stages of transitions might often involve tradeoffs among particle traits, later-and critical-stages are likely to involve the rupture of such tradeoffs. Thus, when observed in the context of ETIs, tradeoff-breaking events stand as a useful marker of these transitions.}, } @article {pmid35972622, year = {2022}, author = {Jacques, F and Baratchart, E and Pienta, KJ and Hammarlund, EU}, title = {Origin and evolution of animal multicellularity in the light of phylogenomics and cancer genetics.}, journal = {Medical oncology (Northwood, London, England)}, volume = {39}, number = {11}, pages = {160}, pmid = {35972622}, issn = {1559-131X}, support = {2019-05254//Vetenskapsrådet/ ; CA163124/CA/NCI NIH HHS/United States ; 949538/ERC_/European Research Council/International ; CA143055/CA/NCI NIH HHS/United States ; U54CA143803/CA/NCI NIH HHS/United States ; CA093900/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Cell Communication ; Cell Differentiation/genetics ; Eukaryota/genetics ; *Neoplasms/genetics ; Phylogeny ; }, abstract = {The rise of animals represents a major but enigmatic event in the evolutionary history of life. In recent years, numerous studies have aimed at understanding the genetic basis of this transition. However, genome comparisons of diverse animal and protist lineages suggest that the appearance of gene families that were previously considered animal specific indeed preceded animals. Animals' unicellular relatives, such as choanoflagellates, ichthyosporeans, and filastereans, demonstrate complex life cycles including transient multicellularity as well as genetic toolkits for temporal cell differentiation, cell-to-cell communication, apoptosis, and cell adhesion. This has warranted further exploration of the genetic basis underlying transitions in cellular organization. An alternative model for the study of transitions in cellular organization is tumors, which exploit physiological programs that characterize both unicellularity and multicellularity. Tumor cells, for example, switch adhesion on and off, up- or downregulate specific cell differentiation states, downregulate apoptosis, and allow cell migration within tissues. Here, we use insights from both the fields of phylogenomics and tumor biology to review the evolutionary history of the regulatory systems of multicellularity and discuss their overlap. We claim that while evolutionary biology has contributed to an increased understanding of cancer, broad investigations into tissue-normal and transformed-can also contribute the framework for exploring animal evolution.}, } @article {pmid35970862, year = {2022}, author = {Smith, TJ and Donoghue, PCJ}, title = {Evolution of fungal phenotypic disparity.}, journal = {Nature ecology & evolution}, volume = {6}, number = {10}, pages = {1489-1500}, pmid = {35970862}, issn = {2397-334X}, support = {BB/T012773/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N000919/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; *Fungi/genetics ; Phenotype ; Plants ; }, abstract = {Organismal-grade multicellularity has been achieved only in animals, plants and fungi. All three kingdoms manifest phenotypically disparate body plans but their evolution has only been considered in detail for animals. Here we tested the general relevance of hypotheses on the evolutionary assembly of animal body plans by characterizing the evolution of fungal phenotypic variety (disparity). The distribution of living fungal form is defined by four distinct morphotypes: flagellated; zygomycetous; sac-bearing; and club-bearing. The discontinuity between morphotypes is a consequence of extinction, indicating that a complete record of fungal disparity would present a more homogeneous distribution of form. Fungal disparity expands episodically through time, punctuated by a sharp increase associated with the emergence of multicellular body plans. Simulations show these temporal trends to be non-random and at least partially shaped by hierarchical contingency. These trends are decoupled from changes in gene number, genome size and taxonomic diversity. Only differences in organismal complexity, characterized as the number of traits that constitute an organism, exhibit a meaningful relationship with fungal disparity. Both animals and fungi exhibit episodic increases in disparity through time, resulting in distributions of form made discontinuous by extinction. These congruences suggest a common mode of multicellular body plan evolution.}, } @article {pmid35948712, year = {2022}, author = {Kim, H and Skinner, DJ and Glass, DS and Hamby, AE and Stuart, BAR and Dunkel, J and Riedel-Kruse, IH}, title = {4-bit adhesion logic enables universal multicellular interface patterning.}, journal = {Nature}, volume = {608}, number = {7922}, pages = {324-329}, pmid = {35948712}, issn = {1476-4687}, support = {R01 GM145893/GM/NIGMS NIH HHS/United States ; }, mesh = {*Algorithms ; *Artificial Cells/cytology ; Biofilms ; *Cell Adhesion ; Humans ; *Logic ; *Synthetic Biology/methods ; }, abstract = {Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions[1,2]. The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning[3,4]. Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems[5-8]. However, our ability to engineer multicellular interface patterns[2,9] is still very limited, as synthetic cell-cell adhesion toolkits and suitable patterning algorithms are underdeveloped[5,7,10-13]. Here we introduce a synthetic cell-cell adhesin logic with swarming bacteria and establish the precise engineering, predictive modelling and algorithmic programming of multicellular interface patterns. We demonstrate interface generation through a swarming adhesion mechanism, quantitative control over interface geometry and adhesion-mediated analogues of developmental organizers and morphogen fields. Using tiling and four-colour-mapping concepts, we identify algorithms for creating universal target patterns. This synthetic 4-bit adhesion logic advances practical applications such as human-readable molecular diagnostics, spatial fluid control on biological surfaces and programmable self-growing materials[5-8,14]. Notably, a minimal set of just four adhesins represents 4 bits of information that suffice to program universal tessellation patterns, implying a low critical threshold for the evolution and engineering of complex multicellular systems[3,5].}, } @article {pmid35946347, year = {2022}, author = {Chen, MY and Teng, WK and Zhao, L and Han, BP and Song, LR and Shu, WS}, title = {Phylogenomics Uncovers Evolutionary Trajectory of Nitrogen Fixation in Cyanobacteria.}, journal = {Molecular biology and evolution}, volume = {39}, number = {9}, pages = {}, pmid = {35946347}, issn = {1537-1719}, mesh = {*Cyanobacteria/genetics ; Gene Transfer, Horizontal ; Nitrogen/metabolism ; *Nitrogen Fixation/genetics ; Photosynthesis/genetics ; Phylogeny ; }, abstract = {Biological nitrogen fixation (BNF) by cyanobacteria is of significant importance for the Earth's biogeochemical nitrogen cycle but is restricted to a few genera that do not form monophyletic group. To explore the evolutionary trajectory of BNF and investigate the driving forces of its evolution, we analyze 650 cyanobacterial genomes and compile the database of diazotrophic cyanobacteria based on the presence of nitrogen fixation gene clusters (NFGCs). We report that 266 of 650 examined genomes are NFGC-carrying members, and these potentially diazotrophic cyanobacteria are unevenly distributed across the phylogeny of Cyanobacteria, that multiple independent losses shaped the scattered distribution. Among the diazotrophic cyanobacteria, two types of NFGC exist, with one being ancestral and abundant, which have descended from diazotrophic ancestors, and the other being anaerobe-like and sparse, possibly being acquired from anaerobic microbes through horizontal gene transfer. Interestingly, we illustrate that the origin of BNF in Cyanobacteria coincide with two major evolutionary events. One is the origin of multicellularity of cyanobacteria, and the other is concurrent genetic innovations with massive gene gains and expansions, implicating their key roles in triggering the evolutionary transition from nondiazotrophic to diazotrophic cyanobacteria. Additionally, we reveal that genes involved in accelerating respiratory electron transport (coxABC), anoxygenic photosynthetic electron transport (sqr), as well as anaerobic metabolisms (pfor, hemN, nrdG, adhE) are enriched in diazotrophic cyanobacteria, representing adaptive genetic signatures that underpin the diazotrophic lifestyle. Collectively, our study suggests that multicellularity, together with concurrent genetic adaptations contribute to the evolution of diazotrophic cyanobacteria.}, } @article {pmid35938723, year = {2022}, author = {Sartor, F and Kovács, ÁT}, title = {Rhythmic Spatial Self-Organization of Bacterial Colonies.}, journal = {mBio}, volume = {13}, number = {4}, pages = {e0170322}, pmid = {35938723}, issn = {2150-7511}, mesh = {Bacteria ; *Circadian Clocks ; Circadian Rhythm/genetics ; Photoperiod ; }, abstract = {Bacteria display a remarkable capacity to organize themselves in space and time within biofilms. Traditionally, the spatial organization of biofilms has been dissected vertically; however, biofilms can exhibit complex, temporally structured, two-dimensional radial patterns while spreading on a surface. Kahl and colleagues report a ring pattern that indicates the alternating redox metabolism of P. aeruginosa biofilms under light/dark cycles. Does the presence of a rhythmic, daily phenotype imply a circadian rhythm? Here, we highlight several examples of rhythmic patterns reported in the literature for surface-colonizing multicellular assemblies and discuss the conceptual requirements for proving the presence of a prokaryotic circadian clock behind pattern formation.}, } @article {pmid35901418, year = {2022}, author = {Raguž, L and Peng, CC and Rutaganira, FUN and Krüger, T and Stanišić, A and Jautzus, T and Kries, H and Kniemeyer, O and Brakhage, AA and King, N and Beemelmanns, C}, title = {Total Synthesis and Functional Evaluation of IORs, Sulfonolipid-based Inhibitors of Cell Differentiation in Salpingoeca rosetta.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {61}, number = {41}, pages = {e202209105}, pmid = {35901418}, issn = {1521-3773}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cell Differentiation ; *Choanoflagellata ; Lipids ; Proteomics ; Sulfonic Acids ; Zinc ; }, abstract = {The choanoflagellate Salpingoeca rosetta is an important model system to study the evolution of multicellularity. In this study we developed a new, modular, and scalable synthesis of sulfonolipid IOR-1A (six steps, 27 % overall yield), which acts as bacterial inhibitor of rosette formation in S. rosetta. The synthesis features a decarboxylative cross-coupling reaction of a sulfonic acid-containing tartaric acid derivative with alkyl zinc reagents. Synthesis of 15 modified IOR-1A derivatives, including fluorescent and photoaffinity-based probes, allowed quantification of IOR-1A, localization studies within S. rosetta cells, and evaluation of structure-activity relations. In a proof of concept study, an inhibitory bifunctional probe was employed in proteomic profiling studies, which allowed to deduce binding partners in bacteria and S. rosetta. These results showcase the power of synthetic chemistry to decipher the biochemical basis of cell differentiation processes within S. rosetta.}, } @article {pmid35894230, year = {2022}, author = {Le Gloanec, C and Collet, L and Silveira, SR and Wang, B and Routier-Kierzkowska, AL and Kierzkowski, D}, title = {Cell type-specific dynamics underlie cellular growth variability in plants.}, journal = {Development (Cambridge, England)}, volume = {149}, number = {14}, pages = {}, doi = {10.1242/dev.200783}, pmid = {35894230}, issn = {1477-9129}, mesh = {*Arabidopsis ; *Arabidopsis Proteins/genetics ; Cell Differentiation/genetics ; Cell Proliferation ; Plant Leaves ; Plant Stomata ; }, abstract = {Coordination of growth, patterning and differentiation is required for shaping organs in multicellular organisms. In plants, cell growth is controlled by positional information, yet the behavior of individual cells is often highly heterogeneous. The origin of this variability is still unclear. Using time-lapse imaging, we determined the source and relevance of cellular growth variability in developing organs of Arabidopsis thaliana. We show that growth is more heterogeneous in the leaf blade than in the midrib and petiole, correlating with higher local differences in growth rates between neighboring cells in the blade. This local growth variability coincides with developing stomata. Stomatal lineages follow a specific, time-dependent growth program that is different from that of their surroundings. Quantification of cellular dynamics in the leaves of a mutant lacking stomata, as well as analysis of floral organs, supports the idea that growth variability is mainly driven by stomata differentiation. Thus, the cell-autonomous behavior of specialized cells is the main source of local growth variability in otherwise homogeneously growing tissue. Those growth differences are buffered by the immediate neighbors of stomata and trichomes to achieve robust organ shapes.}, } @article {pmid35893123, year = {2022}, author = {Dijkwel, Y and Tremethick, DJ}, title = {The Role of the Histone Variant H2A.Z in Metazoan Development.}, journal = {Journal of developmental biology}, volume = {10}, number = {3}, pages = {}, pmid = {35893123}, issn = {2221-3759}, support = {1142399//National Health and Medical Research Council/ ; }, abstract = {During the emergence and radiation of complex multicellular eukaryotes from unicellular ancestors, transcriptional systems evolved by becoming more complex to provide the basis for this morphological diversity. The way eukaryotic genomes are packaged into a highly complex structure, known as chromatin, underpins this evolution of transcriptional regulation. Chromatin structure is controlled by a variety of different epigenetic mechanisms, including the major mechanism for altering the biochemical makeup of the nucleosome by replacing core histones with their variant forms. The histone H2A variant H2A.Z is particularly important in early metazoan development because, without it, embryos cease to develop and die. However, H2A.Z is also required for many differentiation steps beyond the stage that H2A.Z-knockout embryos die. H2A.Z can facilitate the activation and repression of genes that are important for pluripotency and differentiation, and acts through a variety of different molecular mechanisms that depend upon its modification status, its interaction with histone and nonhistone partners, and where it is deposited within the genome. In this review, we discuss the current knowledge about the different mechanisms by which H2A.Z regulates chromatin function at various developmental stages and the chromatin remodeling complexes that determine when and where H2A.Z is deposited.}, } @article {pmid35882195, year = {2022}, author = {Lyng, M and Kovács, ÁT}, title = {Microbial ecology: Metabolic heterogeneity and the division of labor in multicellular structures.}, journal = {Current biology : CB}, volume = {32}, number = {14}, pages = {R771-R774}, doi = {10.1016/j.cub.2022.06.008}, pmid = {35882195}, issn = {1879-0445}, abstract = {Many bacterial species are capable of differentiating to create phenotypic heterogeneity. Using the aggregate-forming marine bacterium Vibrio splendidus, a new study reveals how this organism differentiates to form spherical structures with a motile, carbon-storing core and a non-motile shell.}, } @article {pmid35879542, year = {2022}, author = {Ní Leathlobhair, M and Lenski, RE}, title = {Population genetics of clonally transmissible cancers.}, journal = {Nature ecology & evolution}, volume = {6}, number = {8}, pages = {1077-1089}, pmid = {35879542}, issn = {2397-334X}, mesh = {Animals ; Biological Evolution ; *Genetics, Population ; Genome ; *Neoplasms/genetics ; Population Dynamics ; }, abstract = {Populations of cancer cells are subject to the same core evolutionary processes as asexually reproducing, unicellular organisms. Transmissible cancers are particularly striking examples of these processes. These unusual cancers are clonal lineages that can spread through populations via physical transfer of living cancer cells from one host individual to another, and they have achieved long-term success in the colonization of at least eight different host species. Population genetic theory provides a useful framework for understanding the shift from a multicellular sexual animal into a unicellular asexual clone and its long-term effects on the genomes of these cancers. In this Review, we consider recent findings from transmissible cancer research with the goals of developing an evolutionarily informed perspective on transmissible cancers, examining possible implications for their long-term fate and identifying areas for future research on these exceptional lineages.}, } @article {pmid35862819, year = {2022}, author = {Nies, F and Springstein, BL and Hanke, DM and Dagan, T}, title = {Natural Competence in the Filamentous, Heterocystous Cyanobacterium Chlorogloeopsis fritschii PCC 6912.}, journal = {mSphere}, volume = {7}, number = {4}, pages = {e0099721}, pmid = {35862819}, issn = {2379-5042}, mesh = {*Cyanobacteria/genetics/metabolism ; Gene Transfer, Horizontal ; Photosynthesis ; }, abstract = {Lateral gene transfer plays an important role in the evolution of genetic diversity in prokaryotes. DNA transfer via natural transformation depends on the ability of recipient cells to actively transport DNA from the environment into the cytoplasm, termed natural competence, which relies on the presence of type IV pili and other competence proteins. Natural competence has been described in cyanobacteria for several organisms, including unicellular and filamentous species. However, natural competence in cyanobacteria that differentiate specialized cells for N2-fixation (heterocysts) and form branching or multiseriate cell filaments (termed subsection V) remains unknown. Here, we show that genes essential for natural competence are conserved in subsection V cyanobacteria. Furthermore, using the replicating plasmid pRL25C, we experimentally demonstrate natural competence in a subsection V organism: Chlorogloeopsis fritschii PCC 6912. Our results suggest that natural competence is a common trait in cyanobacteria forming complex cell filament morphologies. IMPORTANCE Cyanobacteria are crucial players in the global biogeochemical cycles, where they contribute to CO2- and N2-fixation. Their main ecological significance is the primary biomass production owing to oxygenic photosynthesis. Cyanobacteria are a diverse phylum, in which the most complex species differentiate specialized cell types and form true-branching or multiseriate cell filament structures (termed subsection V cyanobacteria). These bacteria are considered a peak in the evolution of prokaryotic multicellularity. Among others, species in that group inhabit fresh and marine water habitats, soil, and extreme habitats such as thermal springs. Here, we show that the core genes required for natural competence are frequent in subsection V cyanobacteria and demonstrate for the first time natural transformation in a member of subsection V. The prevalence of natural competence has implications for the role of DNA acquisition in the genome evolution of cyanobacteria. Furthermore, the presence of mechanisms for natural transformation opens up new possibilities for the genetic modification of subsection V cyanobacteria.}, } @article {pmid35862435, year = {2022}, author = {Howe, J and Rink, JC and Wang, B and Griffin, AS}, title = {Multicellularity in animals: The potential for within-organism conflict.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {32}, pages = {e2120457119}, pmid = {35862435}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; *Cell Lineage ; Clone Cells ; Developmental Biology ; *Insecta/growth & development ; Reproduction ; }, abstract = {Metazoans function as individual organisms but also as "colonies" of cells whose single-celled ancestors lived and reproduced independently. Insights from evolutionary biology about multicellular group formation help us understand the behavior of cells: why they cooperate, and why cooperation sometimes breaks down. Current explanations for multicellularity focus on two aspects of development which promote cooperation and limit conflict among cells: a single-cell bottleneck, which creates organisms composed of clones, and a separation of somatic and germ cell lineages, which reduces the selective advantage of cheating. However, many obligately multicellular organisms thrive with neither, creating the potential for within-organism conflict. Here, we argue that the prevalence of such organisms throughout the Metazoa requires us to refine our preconceptions of conflict-free multicellularity. Evolutionary theory must incorporate developmental mechanisms across a broad range of organisms-such as unusual reproductive strategies, totipotency, and cell competition-while developmental biology must incorporate evolutionary principles. To facilitate this cross-disciplinary approach, we provide a conceptual overview from evolutionary biology for developmental biologists, using analogous examples in the well-studied social insects.}, } @article {pmid35858311, year = {2022}, author = {Belcher, LJ and Madgwick, PG and Kuwana, S and Stewart, B and Thompson, CRL and Wolf, JB}, title = {Developmental constraints enforce altruism and avert the tragedy of the commons in a social microbe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {29}, pages = {e2111233119}, pmid = {35858311}, issn = {1091-6490}, support = {BB/M01035X/1//UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; BB/M007146/1//UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; NE/V012002/1//UKRI | Natural Environment Research Council (NERC)/ ; WT095643AIA//Wellcome Trust (WT)/ ; }, mesh = {*Altruism ; Biological Evolution ; Cooperative Behavior ; *Dictyostelium ; Humans ; Motivation ; }, abstract = {Organisms often cooperate through the production of freely available public goods. This can greatly benefit the group but is vulnerable to the "tragedy of the commons" if individuals lack the motivation to make the necessary investment into public goods production. Relatedness to groupmates can motivate individual investment because group success ultimately benefits their genes' own self-interests. However, systems often lack mechanisms that can reliably ensure that relatedness is high enough to promote cooperation. Consequently, groups face a persistent threat from the tragedy unless they have a mechanism to enforce investment when relatedness fails to provide adequate motivation. To understand the real threat posed by the tragedy and whether groups can avert its impact, we determine how the social amoeba Dictyostelium discoideum responds as relatedness decreases to levels that should induce the tragedy. We find that, while investment in public goods declines as overall within-group relatedness declines, groups avert the expected catastrophic collapse of the commons by continuing to invest, even when relatedness should be too low to incentivize any contribution. We show that this is due to a developmental buffering system that generates enforcement because insufficient cooperation perturbs the balance of a negative feedback system controlling multicellular development. This developmental constraint enforces investment under the conditions expected to be most tragic, allowing groups to avert a collapse in cooperation. These results help explain how mechanisms that suppress selfishness and enforce cooperation can arise inadvertently as a by-product of constraints imposed by selection on different traits.}, } @article {pmid35853599, year = {2023}, author = {Arjoca, S and Robu, A and Neagu, M and Neagu, A}, title = {Mathematical and computational models in spheroid-based biofabrication.}, journal = {Acta biomaterialia}, volume = {165}, number = {}, pages = {125-139}, doi = {10.1016/j.actbio.2022.07.024}, pmid = {35853599}, issn = {1878-7568}, mesh = {*Tissue Engineering/methods ; Models, Theoretical ; Computer Simulation ; Organoids ; *Bioprinting/methods ; Printing, Three-Dimensional ; Tissue Scaffolds/chemistry ; }, abstract = {Ubiquitous in embryonic development, tissue fusion is of interest to tissue engineers who use tissue spheroids or organoids as building blocks of three-dimensional (3D) multicellular constructs. This review presents mathematical models and computer simulations of the fusion of tissue spheroids. The motivation of this study stems from the need to predict the post-printing evolution of 3D bioprinted constructs. First, we provide a brief overview of differential adhesion, the main morphogenetic mechanism involved in post-printing structure formation. It will be shown that clusters of cohesive cells behave as an incompressible viscous fluid on the time scale of hours. The discussion turns then to mathematical models based on the continuum hydrodynamics of highly viscous liquids and on statistical mechanics. Next, we analyze the validity and practical use of computational models of multicellular self-assembly in live constructs created by tissue spheroid bioprinting. Finally, we discuss the perspectives of the field as machine learning starts to reshape experimental design, and modular robotic workstations tend to alleviate the burden of repetitive tasks in biofabrication. STATEMENT OF SIGNIFICANCE: Bioprinted constructs are living systems, which evolve via morphogenetic mechanisms known from developmental biology. This review presents mathematical and computational tools devised for modeling post-printing structure formation. They help achieving a desirable outcome without expensive optimization experiments. While previous reviews mainly focused on assumptions, technical details, strengths, and limitations of computational models of multicellular self-assembly, this article discusses their validity and practical use in biofabrication. It also presents an overview of mathematical models that proved to be useful in the evaluation of experimental data on tissue spheroid fusion, and in the calibration of computational models. Finally, the perspectives of the field are discussed in the advent of robotic biofabrication platforms and bioprinting process optimization by machine learning.}, } @article {pmid35852417, year = {2022}, author = {Chakravarty, AK and McGrail, DJ and Lozanoski, TM and Dunn, BS and Shih, DJH and Cirillo, KM and Cetinkaya, SH and Zheng, WJ and Mills, GB and Yi, SS and Jarosz, DF and Sahni, N}, title = {Biomolecular Condensation: A New Phase in Cancer Research.}, journal = {Cancer discovery}, volume = {12}, number = {9}, pages = {2031-2043}, pmid = {35852417}, issn = {2159-8290}, support = {K99 GM128180/GM/NIGMS NIH HHS/United States ; R35 GM137836/GM/NIGMS NIH HHS/United States ; K99 CA240689/CA/NCI NIH HHS/United States ; DRG2221-15/HHMI/Howard Hughes Medical Institute/United States ; U01 CA217842/CA/NCI NIH HHS/United States ; R35 GM133658/GM/NIGMS NIH HHS/United States ; DP2 GM119140/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Neoplasms/metabolism ; *Organelles/metabolism ; Research ; }, abstract = {UNLABELLED: Multicellularity was a watershed development in evolution. However, it also meant that individual cells could escape regulatory mechanisms that restrict proliferation at a severe cost to the organism: cancer. From the standpoint of cellular organization, evolutionary complexity scales to organize different molecules within the intracellular milieu. The recent realization that many biomolecules can "phase-separate" into membraneless organelles, reorganizing cellular biochemistry in space and time, has led to an explosion of research activity in this area. In this review, we explore mechanistic connections between phase separation and cancer-associated processes and emerging examples of how these become deranged in malignancy.

SIGNIFICANCE: One of the fundamental functions of phase separation is to rapidly and dynamically respond to environmental perturbations. Importantly, these changes often lead to alterations in cancer-relevant pathways and processes. This review covers recent advances in the field, including emerging principles and mechanisms of phase separation in cancer.}, } @article {pmid35849348, year = {2022}, author = {Wu, TY and Hoh, KL and Boonyaves, K and Krishnamoorthi, S and Urano, D}, title = {Diversification of heat shock transcription factors expanded thermal stress responses during early plant evolution.}, journal = {The Plant cell}, volume = {34}, number = {10}, pages = {3557-3576}, pmid = {35849348}, issn = {1532-298X}, mesh = {*Arabidopsis/metabolism ; Gene Expression Regulation, Plant/genetics ; Gene Regulatory Networks ; Heat Shock Transcription Factors/metabolism ; Heat-Shock Response/genetics ; *Marchantia/genetics/metabolism ; Plant Proteins/genetics/metabolism ; }, abstract = {The copy numbers of many plant transcription factor (TF) genes substantially increased during terrestrialization. This allowed TFs to acquire new specificities and thus create gene regulatory networks (GRNs) with new biological functions to help plants adapt to terrestrial environments. Through characterizing heat shock factor (HSF) genes MpHSFA1 and MpHSFB1 in the liverwort Marchantia polymorpha, we explored how heat-responsive GRNs widened their functions in M. polymorpha and Arabidopsis thaliana. An interspecies comparison of heat-induced transcriptomes and the evolutionary rates of HSFs demonstrated the emergence and subsequent rapid evolution of HSFB prior to terrestrialization. Transcriptome and metabolome analyses of M. polymorpha HSF-null mutants revealed that MpHSFA1 controls canonical heat responses such as thermotolerance and metabolic changes. MpHSFB1 also plays essential roles in heat responses, as well as regulating developmental processes including meristem branching and antheridiophore formation. Analysis of cis-regulatory elements revealed development- and stress-related TFs that function directly or indirectly downstream of HSFB. Male gametophytes of M. polymorpha showed higher levels of thermotolerance than female gametophytes, which could be explained by different expression levels of MpHSFA1U and MpHSFA1V on sex chromosome. We propose that the diversification of HSFs is linked to the expansion of HS responses, which enabled coordinated multicellular reactions in land plants.}, } @article {pmid35841659, year = {2022}, author = {Gabaldón, T and Völcker, E and Torruella, G}, title = {On the Biology, Diversity and Evolution of Nucleariid Amoebae (Amorphea, Obazoa, Opisthokonta[1].}, journal = {Protist}, volume = {173}, number = {4}, pages = {125895}, doi = {10.1016/j.protis.2022.125895}, pmid = {35841659}, issn = {1618-0941}, mesh = {*Amoeba ; Animals ; Biology ; Eukaryota ; Fungi ; Phylogeny ; }, abstract = {Nucleariids are a small group of free-living heterotrophic amoebae. Although these organisms present a variety of cell sizes and cell coverings, they are mostly spherical cells with radiating filopodia, sometimes with several nuclei. Nuclearia, the genus that gives the name to the group, contains species that are opportunistic consumers of detritus, bacteria, and algae. The beautiful Pompholyxophrys is covered with endogenous siliceous pearls. Lithocolla covers itself with sand particles, or otherwise diatom frustules. The tiny Parvularia exclusively feeds on bacteria, and Fonticula is adapted to solid substrates and presents aggregative multicellular stages. Nucleariids belong to the Opisthokonta, which comprise animals, fungi, and their protist relatives, and form the earliest branch in the holomycotan clade (fungi and closest relatives). Hence, they are key for understanding the origin and diversification of Opisthokonta, an eukaryotic supergroup that contains organisms with different feeding modes, life-styles, and cell organizations. In this review, the reader will find an introduction to nucleariids, from their discovery in the 19th century until the most recent studies. It summarizes available information on their morphology, life history, cell organisation, ecology, diversity, systematics and evolution.}, } @article {pmid35838349, year = {2022}, author = {Meléndez García, R and Haccard, O and Chesneau, A and Narassimprakash, H and Roger, J and Perron, M and Marheineke, K and Bronchain, O}, title = {A non-transcriptional function of Yap regulates the DNA replication program in Xenopus laevis.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35838349}, issn = {2050-084X}, mesh = {Animals ; DNA Replication ; DNA Replication Timing ; *Replication Origin ; S Phase/genetics ; *Telomere-Binding Proteins/genetics ; Xenopus laevis/genetics/metabolism ; }, abstract = {In multicellular eukaryotic organisms, the initiation of DNA replication occurs asynchronously throughout S-phase according to a regulated replication timing program. Here, using Xenopus egg extracts, we showed that Yap (Yes-associated protein 1), a downstream effector of the Hippo signalling pathway, is required for the control of DNA replication dynamics. We found that Yap is recruited to chromatin at the start of DNA replication and identified Rif1, a major regulator of the DNA replication timing program, as a novel Yap binding protein. Furthermore, we show that either Yap or Rif1 depletion accelerates DNA replication dynamics by increasing the number of activated replication origins. In Xenopus embryos, using a Trim-Away approach during cleavage stages devoid of transcription, we found that either Yap or Rif1 depletion triggers an acceleration of cell divisions, suggesting a shorter S-phase by alterations of the replication program. Finally, our data show that Rif1 knockdown leads to defects in the partitioning of early versus late replication foci in retinal stem cells, as we previously showed for Yap. Altogether, our findings unveil a non-transcriptional role for Yap in regulating replication dynamics. We propose that Yap and Rif1 function as brakes to control the DNA replication program in early embryos and post-embryonic stem cells.}, } @article {pmid35835876, year = {2022}, author = {Marcon, L}, title = {Multicellular self-organization.}, journal = {Nature reviews. Molecular cell biology}, volume = {23}, number = {12}, pages = {777}, pmid = {35835876}, issn = {1471-0080}, mesh = {*Biological Evolution ; }, } @article {pmid35821097, year = {2022}, author = {Wright, CJ and Smith, CWJ and Jiggins, CD}, title = {Alternative splicing as a source of phenotypic diversity.}, journal = {Nature reviews. Genetics}, volume = {23}, number = {11}, pages = {697-710}, pmid = {35821097}, issn = {1471-0064}, support = {206194/WT_/Wellcome Trust/United Kingdom ; 218328/WT_/Wellcome Trust/United Kingdom ; BB/R007500/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 209368/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Alternative Splicing ; Biological Evolution ; Phenotype ; Proteins/genetics ; *RNA Splicing ; }, abstract = {A major goal of evolutionary genetics is to understand the genetic processes that give rise to phenotypic diversity in multicellular organisms. Alternative splicing generates multiple transcripts from a single gene, enriching the diversity of proteins and phenotypic traits. It is well established that alternative splicing contributes to key innovations over long evolutionary timescales, such as brain development in bilaterians. However, recent developments in long-read sequencing and the generation of high-quality genome assemblies for diverse organisms has facilitated comparisons of splicing profiles between closely related species, providing insights into how alternative splicing evolves over shorter timescales. Although most splicing variants are probably non-functional, alternative splicing is nonetheless emerging as a dynamic, evolutionarily labile process that can facilitate adaptation and contribute to species divergence.}, } @article {pmid35804300, year = {2022}, author = {Angaroni, F and Guidi, A and Ascolani, G and d'Onofrio, A and Antoniotti, M and Graudenzi, A}, title = {J-SPACE: a Julia package for the simulation of spatial models of cancer evolution and of sequencing experiments.}, journal = {BMC bioinformatics}, volume = {23}, number = {1}, pages = {269}, pmid = {35804300}, issn = {1471-2105}, support = {Bicocca 2020 Starting Grant//Università degli Studi di Milano-Bicocca/ ; 22790/CRUK_/Cancer Research UK/United Kingdom ; 22790/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Computer Simulation ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Neoplasms/genetics/pathology ; Phylogeny ; *Software ; }, abstract = {BACKGROUND: The combined effects of biological variability and measurement-related errors on cancer sequencing data remain largely unexplored. However, the spatio-temporal simulation of multi-cellular systems provides a powerful instrument to address this issue. In particular, efficient algorithmic frameworks are needed to overcome the harsh trade-off between scalability and expressivity, so to allow one to simulate both realistic cancer evolution scenarios and the related sequencing experiments, which can then be used to benchmark downstream bioinformatics methods.

RESULT: We introduce a Julia package for SPAtial Cancer Evolution (J-SPACE), which allows one to model and simulate a broad set of experimental scenarios, phenomenological rules and sequencing settings.Specifically, J-SPACE simulates the spatial dynamics of cells as a continuous-time multi-type birth-death stochastic process on a arbitrary graph, employing different rules of interaction and an optimised Gillespie algorithm. The evolutionary dynamics of genomic alterations (single-nucleotide variants and indels) is simulated either under the Infinite Sites Assumption or several different substitution models, including one based on mutational signatures. After mimicking the spatial sampling of tumour cells, J-SPACE returns the related phylogenetic model, and allows one to generate synthetic reads from several Next-Generation Sequencing (NGS) platforms, via the ART read simulator. The results are finally returned in standard FASTA, FASTQ, SAM, ALN and Newick file formats.

CONCLUSION: J-SPACE is designed to efficiently simulate the heterogeneous behaviour of a large number of cancer cells and produces a rich set of outputs. Our framework is useful to investigate the emergent spatial dynamics of cancer subpopulations, as well as to assess the impact of incomplete sampling and of experiment-specific errors. Importantly, the output of J-SPACE is designed to allow the performance assessment of downstream bioinformatics pipelines processing NGS data. J-SPACE is freely available at: https://github.com/BIMIB-DISCo/J-Space.jl .}, } @article {pmid35792830, year = {2022}, author = {Fukai, E and Yoshikawa, M and Shah, N and Sandal, N and Miyao, A and Ono, S and Hirakawa, H and Akyol, TY and Umehara, Y and Nonomura, KI and Stougaard, J and Hirochika, H and Hayashi, M and Sato, S and Andersen, SU and Okazaki, K}, title = {Widespread and transgenerational retrotransposon activation in inter- and intraspecies recombinant inbred populations of Lotus japonicus.}, journal = {The Plant journal : for cell and molecular biology}, volume = {111}, number = {5}, pages = {1397-1410}, doi = {10.1111/tpj.15896}, pmid = {35792830}, issn = {1365-313X}, mesh = {Evolution, Molecular ; Genome, Plant/genetics ; Hybridization, Genetic ; *Lotus/genetics ; Plants/genetics ; *Retroelements/genetics ; Terminal Repeat Sequences/genetics ; }, abstract = {Transposable elements (TEs) constitute a large proportion of genomes of multicellular eukaryotes, including flowering plants. TEs are normally maintained in a silenced state and their transpositions rarely occur. Hybridization between distant species has been regarded as a 'shock' that stimulates genome reorganization, including TE mobilization. However, whether crosses between genetically close parents that result in viable and fertile offspring can induce TE transpositions has remained unclear. Here, we investigated the activation of long terminal repeat (LTR) retrotransposons in three Lotus japonicus recombinant inbred line (RIL) populations. We found that at least six LTR retrotransposon families were activated and transposed in 78% of the RILs investigated. LORE1a, one of the transposed LTR retrotransposons, showed transgenerational epigenetic activation, indicating the long-term effects of epigenetic instability induced by hybridization. Our study highlights TE activation as an unexpectedly common event in plant reproduction.}, } @article {pmid35790840, year = {2022}, author = {Beljan, S and Dominko, K and Talajić, A and Hloušek-Kasun, A and Škrobot Vidaček, N and Herak Bosnar, M and Vlahoviček, K and Ćetković, H}, title = {Structure and function of cancer-related developmentally regulated GTP-binding protein 1 (DRG1) is conserved between sponges and humans.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {11379}, pmid = {35790840}, issn = {2045-2322}, mesh = {Animals ; GTP-Binding Proteins ; Genomics ; Humans ; *Neoplasms/genetics ; *Oncogenes ; RNA ; Transcription Factors ; }, abstract = {Cancer is a disease caused by errors within the multicellular system and it represents a major health issue in multicellular organisms. Although cancer research has advanced substantially, new approaches focusing on fundamental aspects of cancer origin and mechanisms of spreading are necessary. Comparative genomic studies have shown that most genes linked to human cancer emerged during the early evolution of Metazoa. Thus, basal animals without true tissues and organs, such as sponges (Porifera), might be an innovative model system for understanding the molecular mechanisms of proteins involved in cancer biology. One of these proteins is developmentally regulated GTP-binding protein 1 (DRG1), a GTPase stabilized by interaction with DRG family regulatory protein 1 (DFRP1). This study reveals a high evolutionary conservation of DRG1 gene/protein in metazoans. Our biochemical analysis and structural predictions show that both recombinant sponge and human DRG1 are predominantly monomers that form complexes with DFRP1 and bind non-specifically to RNA and DNA. We demonstrate the conservation of sponge and human DRG1 biological features, including intracellular localization and DRG1:DFRP1 binding, function of DRG1 in α-tubulin dynamics, and its role in cancer biology demonstrated by increased proliferation, migration and colonization in human cancer cells. These results suggest that the ancestor of all Metazoa already possessed DRG1 that is structurally and functionally similar to the human DRG1, even before the development of real tissues or tumors, indicating an important function of DRG1 in fundamental cellular pathways.}, } @article {pmid35778439, year = {2022}, author = {Belpaire, TER and Pešek, J and Lories, B and Verstrepen, KJ and Steenackers, HP and Ramon, H and Smeets, B}, title = {Permissive aggregative group formation favors coexistence between cooperators and defectors in yeast.}, journal = {The ISME journal}, volume = {16}, number = {10}, pages = {2305-2312}, pmid = {35778439}, issn = {1751-7370}, support = {12Z6118N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; CELSA/18/031//KU Leuven (Katholieke Universiteit Leuven)/ ; C24/18/046//KU Leuven/ ; }, mesh = {Biological Evolution ; Flocculation ; Mannose-Binding Lectins/chemistry/genetics/metabolism ; *Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism ; }, abstract = {In Saccharomyces cerevisiae, the FLO1 gene encodes flocculins that lead to formation of multicellular flocs, that offer protection to the constituent cells. Flo1p was found to preferentially bind to fellow cooperators compared to defectors lacking FLO1 expression, enriching cooperators within the flocs. Given this dual function in cooperation and kin recognition, FLO1 has been termed a "green beard gene". Because of the heterophilic nature of the Flo1p bond however, we hypothesize that kin recognition is permissive and depends on the relative stability of the FLO1[+]/flo1[-] versus FLO1[+]/FLO1[+] detachment force F. We combine single-cell measurements of adhesion, individual cell-based simulations of cluster formation, and in vitro flocculation to study the impact of relative bond stability on the evolutionary stability of cooperation. We identify a trade-off between both aspects of the green beard mechanism, with reduced relative bond stability leading to increased kin recognition at the expense of cooperative benefits. We show that the fitness of FLO1 cooperators decreases as their frequency in the population increases, arising from the observed permissive character (F+- = 0.5 F++) of the Flo1p bond. Considering the costs associated with FLO1 expression, this asymmetric selection often results in a stable coexistence between cooperators and defectors.}, } @article {pmid35774229, year = {2022}, author = {Kaluthantrige Don, F and Kalebic, N}, title = {Forebrain Organoids to Model the Cell Biology of Basal Radial Glia in Neurodevelopmental Disorders and Brain Evolution.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {917166}, pmid = {35774229}, issn = {2296-634X}, abstract = {The acquisition of higher intellectual abilities that distinguish humans from their closest relatives correlates greatly with the expansion of the cerebral cortex. This expansion is a consequence of an increase in neuronal cell production driven by the higher proliferative capacity of neural progenitor cells, in particular basal radial glia (bRG). Furthermore, when the proliferation of neural progenitor cells is impaired and the final neuronal output is altered, severe neurodevelopmental disorders can arise. To effectively study the cell biology of human bRG, genetically accessible human experimental models are needed. With the pioneering success to isolate and culture pluripotent stem cells in vitro, we can now routinely investigate the developing human cerebral cortex in a dish using three-dimensional multicellular structures called organoids. Here, we will review the molecular and cell biological features of bRG that have recently been elucidated using brain organoids. We will further focus on the application of this simple model system to study in a mechanistically actionable way the molecular and cellular events in bRG that can lead to the onset of various neurodevelopmental diseases.}, } @article {pmid35756025, year = {2022}, author = {Chen, S and Yu, M and Zhang, W and He, K and Pan, H and Cui, K and Zhao, Y and Zhang, XH and Xiao, T and Zhang, W and Wu, LF}, title = {Metagenomic and Microscopic Analysis of Magnetotactic Bacteria in Tangyin Hydrothermal Field of Okinawa Trough.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {887136}, pmid = {35756025}, issn = {1664-302X}, abstract = {Magnetotactic bacteria (MTB) have been found in a wide variety of marine habitats, ranging from intertidal sediments to deep-sea seamounts. Deep-sea hydrothermal fields are rich in metal sulfides, which are suitable areas for the growth of MTB. However, MTB in hydrothermal fields have never been reported. Here, the presence of MTB in sediments from the Tangyin hydrothermal field was analyzed by 16S rRNA gene amplicon analysis, metagenomics, and transmission electron microscopy. Sequencing 16S rRNA gene yielded a total of 709 MTB sequences belonging to 20 OTUs, affiliated with Desulfobacterota, Alphaproteobacteria, and Nitrospirae. Three shapes of magnetofossil were identified by transmission electron microscopy: elongated-prismatic, bullet-shaped, and cuboctahedron. All of these structures were composed of Fe3O4. A total of 121 sequences were found to be homologous to the published MTB magnetosome-function-related genes, and relevant domains were identified. Further analysis revealed that diverse MTB are present in the Tangyin hydrothermal field, and that multicellular magnetotactic prokaryote (MMPs) might be the dominant MTB.}, } @article {pmid35754813, year = {2022}, author = {Wang, H and Umer, MJ and Liu, F and Cai, X and Zheng, J and Xu, Y and Hou, Y and Zhou, Z}, title = {Genome-Wide Identification and Characterization of CPR5 Genes in Gossypium Reveals Their Potential Role in Trichome Development.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {921096}, pmid = {35754813}, issn = {1664-8021}, abstract = {Trichomes protect plants against insects, microbes, herbivores, and abiotic damages and assist seed dispersal. The function of CPR5 genes have been found to be involved in the trichome development but the research on the underlying genetic and molecular mechanisms are extremely limited. Herein, genome wide identification and characterization of CPR5 genes was performed. In total, 26 CPR5 family members were identified in Gossypium species. Phylogenetic analysis, structural characteristics, and synteny analysis of CPR5s showed the conserved evolution relationships of CPR5. The promoter analysis of CPR5 genes revealed hormone, stress, and development-related cis-elements. Gene ontology (GO) enrichment analysis showed that the CPR5 genes were largely related to biological regulation, developmental process, multicellular organismal process. Protein-protein interaction analysis predicted several trichome development related proteins (SIM, LGO, and GRL) directly interacting with CPR5 genes. Further, nine putative Gossypium-miRNAs were also identified, targeting Gossypium CPR5 genes. RNA-Seq data of G. arboreum (with trichomes) and G. herbaceum (with no trichomes) was used to perform the co-expression network analysis. GheCPR5.1 was identified as a hub gene in a co-expression network analysis. RT-qPCR of GheCPR5.1 gene in different tissues suggests that this gene has higher expressions in the petiole and might be a key candidate involved in the trichome development. Virus induced gene silencing of GheCPR5.1 (Ghe02G17590) confirms its role in trichome development and elongation. Current results provide proofs of the possible role of CPR5 genes and provide preliminary information for further studies of GheCPR5.1 functions in trichome development.}, } @article {pmid35728616, year = {2022}, author = {Cameron-Pack, ME and König, SG and Reyes-Guevara, A and Reyes-Prieto, A and Nedelcu, AM}, title = {A personal cost of cheating can stabilize reproductive altruism during the early evolution of clonal multicellularity.}, journal = {Biology letters}, volume = {18}, number = {6}, pages = {20220059}, pmid = {35728616}, issn = {1744-957X}, mesh = {*Altruism ; Biological Evolution ; Reproduction ; *Volvox/genetics ; }, abstract = {Understanding how cooperation evolved and is maintained remains an important and often controversial topic because cheaters that reap the benefits of cooperation without paying the costs can threaten the evolutionary stability of cooperative traits. Cooperation-and especially reproductive altruism-is particularly relevant to the evolution of multicellularity, as somatic cells give up their reproductive potential in order to contribute to the fitness of the newly emerged multicellular individual. Here, we investigated cheating in a simple multicellular species-the green alga Volvox carteri, in the context of the mechanisms that can stabilize reproductive altruism during the early evolution of clonal multicellularity. We found that the benefits cheater mutants can gain in terms of their own reproduction are pre-empted by a cost in survival due to increased sensitivity to stress. This personal cost of cheating reflects the antagonistic pleiotropic effects that the gene coding for reproductive altruism-regA-has at the cell level. Specifically, the expression of regA in somatic cells results in the suppression of their reproduction potential but also confers them with increased resistance to stress. Since regA evolved from a life-history trade-off gene, we suggest that co-opting trade-off genes into cooperative traits can provide a built-in safety system against cheaters in other clonal multicellular lineages.}, } @article {pmid35726057, year = {2022}, author = {Kaufmann, M and Schaupp, AL and Sun, R and Coscia, F and Dendrou, CA and Cortes, A and Kaur, G and Evans, HG and Mollbrink, A and Navarro, JF and Sonner, JK and Mayer, C and DeLuca, GC and Lundeberg, J and Matthews, PM and Attfield, KE and Friese, MA and Mann, M and Fugger, L}, title = {Identification of early neurodegenerative pathways in progressive multiple sclerosis.}, journal = {Nature neuroscience}, volume = {25}, number = {7}, pages = {944-955}, pmid = {35726057}, issn = {1546-1726}, support = {MC_UU_00008/3/MRC_/Medical Research Council/United Kingdom ; MC_UU_12010/3/MRC_/Medical Research Council/United Kingdom ; 100308/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {*Central Nervous System Diseases/complications ; Disease Progression ; Humans ; *Multiple Sclerosis/pathology ; Neurons/metabolism ; Proteomics ; }, abstract = {Progressive multiple sclerosis (MS) is characterized by unrelenting neurodegeneration, which causes cumulative disability and is refractory to current treatments. Drug development to prevent disease progression is an urgent clinical need yet is constrained by an incomplete understanding of its complex pathogenesis. Using spatial transcriptomics and proteomics on fresh-frozen human MS brain tissue, we identified multicellular mechanisms of progressive MS pathogenesis and traced their origin in relation to spatially distributed stages of neurodegeneration. By resolving ligand-receptor interactions in local microenvironments, we discovered defunct trophic and anti-inflammatory intercellular communications within areas of early neuronal decline. Proteins associated with neuronal damage in patient samples showed mechanistic concordance with published in vivo knockdown and central nervous system (CNS) disease models, supporting their causal role and value as potential therapeutic targets in progressive MS. Our findings provide a new framework for drug development strategies, rooted in an understanding of the complex cellular and signaling dynamics in human diseased tissue that facilitate this debilitating disease.}, } @article {pmid35725583, year = {2022}, author = {Mori, G and Delfino, D and Pibiri, P and Rivetti, C and Percudani, R}, title = {Origin and significance of the human DNase repertoire.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {10364}, pmid = {35725583}, issn = {2045-2322}, mesh = {Animals ; DNA/genetics ; Deoxyribonuclease I/genetics ; *Deoxyribonucleases/genetics ; *Evolution, Molecular ; Fishes/genetics ; Gene Duplication ; Humans ; Phylogeny ; Synteny ; Vertebrates/genetics ; }, abstract = {The human genome contains four DNase1 and two DNase2 genes. The origin and functional specialization of this repertoire are not fully understood. Here we use genomics and transcriptomics data to infer the evolutionary history of DNases and investigate their biological significance. Both DNase1 and DNase2 families have expanded in vertebrates since ~ 650 million years ago before the divergence of jawless and jawed vertebrates. DNase1, DNase1L1, and DNase1L3 co-existed in jawless fish, whereas DNase1L2 originated in amniotes by tandem duplication of DNase1. Among the non-human DNases, DNase1L4 and newly identified DNase1L5 derived from early duplications that were lost in terrestrial vertebrates. The ancestral gene of the DNase2 family, DNase2b, has been conserved in synteny with the Uox gene across 700 million years of animal evolution,while DNase2 originated in jawless fish. DNase1L1 acquired a GPI-anchor for plasma membrane attachment in bony fishes, and DNase1L3 acquired a C-terminal basic peptide for the degradation of microparticle DNA in jawed vertebrates. The appearance of DNase1L2, with a distinct low pH optimum and skin localization, is among the amniote adaptations to life on land. The expansion of the DNase repertoire in vertebrates meets the diversified demand for DNA debris removal in complex multicellular organisms.}, } @article {pmid35713948, year = {2022}, author = {Passer, AR and Clancey, SA and Shea, T and David-Palma, M and Averette, AF and Boekhout, T and Porcel, BM and Nowrousian, M and Cuomo, CA and Sun, S and Heitman, J and Coelho, MA}, title = {Obligate sexual reproduction of a homothallic fungus closely related to the Cryptococcus pathogenic species complex.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35713948}, issn = {2050-084X}, support = {R01 AI039115/AI/NIAID NIH HHS/United States ; R01 AI050113/AI/NIAID NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; }, mesh = {Biological Evolution ; *Cryptococcus neoformans/genetics ; *Genes, Mating Type, Fungal/genetics ; Humans ; Reproduction ; Saccharomyces cerevisiae/genetics ; }, abstract = {eLife digest. Fungi are enigmatic organisms that flourish in soil, on decaying plants, or during infection of animals or plants. Growing in myriad forms, from single-celled yeast to multicellular molds and mushrooms, fungi have also evolved a variety of strategies to reproduce. Normally, fungi reproduce in one of two ways: either they reproduce asexually, with one individual producing a new individual identical to itself, or they reproduce sexually, with two individuals of different 'mating types' contributing to produce a new individual. However, individuals of some species exhibit 'homothallism' or self-fertility: these individuals can produce reproductive cells that are universally compatible, and therefore can reproduce sexually with themselves or with any other cell in the population. Homothallism has evolved multiple times throughout the fungal kingdom, suggesting it confers advantage when population numbers are low or mates are hard to find. Yet some homothallic fungi been overlooked compared to heterothallic species, whose mating types have been well characterised. Understanding the genetic basis of homothallism and how it evolved in different species can provide insights into pathogenic species that cause fungal disease. With that in mind, Passer, Clancey et al. explored the genetic basis of homothallism in Cryptococcus depauperatus, a close relative of C. neoformans, a species that causes fungal infections in humans. A combination of genetic sequencing techniques and experiments were applied to analyse, compare, and manipulate C. depauperatus' genome to see how this species evolved self-fertility. Passer, Clancey et al. showed that C. depauperatus evolved the ability to reproduce sexually by itself via a unique evolutionary pathway. The result is a form of homothallism never reported in fungi before. C. depauperatus lost some of the genes that control mating in other species of fungi, and acquired genes from the opposing mating types of a heterothallic ancestor to become self-fertile. Passer, Clancey et al. also found that, unlike other Cryptococcus species that switch between asexual and sexual reproduction, C. depauperatus grows only as long, branching filaments called hyphae, a sexual form. The species reproduces sexually with itself throughout its life cycle and is unable to produce a yeast (asexual) form, in contrast to other closely related species. This work offers new insights into how different modes of sexual reproduction have evolved in fungi. It also provides another interesting case of how genome plasticity and evolutionary pressures can produce similar outcomes, homothallism, via different evolutionary paths. Lastly, assembling the complete genome of C. depauperatus will foster comparative studies between pathogenic and non-pathogenic Cryptococcus species.}, } @article {pmid35685010, year = {2022}, author = {Barthlott, W and Büdel, B and Mail, M and Neumann, KM and Bartels, D and Fischer, E}, title = {Superhydrophobic Terrestrial Cyanobacteria and Land Plant Transition.}, journal = {Frontiers in plant science}, volume = {13}, number = {}, pages = {880439}, pmid = {35685010}, issn = {1664-462X}, abstract = {Plants and other organisms have evolved structures and mechanisms for colonizing land since the Early Ordovician. In this context, their surfaces, the crucial physical interface with the environment, are mainly considered barriers against water loss. It is suggested that extreme water repellency (superhydrophobicity) was an additional key innovation for the transition of algae from water to land some 400 mya. Superhydrophobicity enhances gas exchange on land and excludes aquatic competitors in water films. In a different context, in material science and surface technology, superhydrophobicity has also become one of the most important bioinspired innovations enabling the avoidance of water films and contamination. Here, we present data for an extremely water-repellent cyanobacterial biofilm of the desiccation tolerant Hassallia byssoidea providing evidence for a much earlier prokaryotic Precambrian (ca. 1-2 bya) origin of superhydrophobicity and chemical heterogeneities associated with land transition. The multicellular cyanobacterium is functionally differentiated in a submerged basal hydrophilic absorbing portion like a "rhizoid" and an upright emersed superhydrophobic "phyllocauloid" filament for assimilation, nitrogen fixation, and splash dispersed diaspores. Additional data are provided for superhydrophobic surfaces in terrestrial green algae and in virtually all ancestral land plants (Bryophytes, ferns and allies, Amborella, Nelumbo), slime molds, and fungi. Rethinking of superhydrophobicity as an essential first step for life in terrestrial environments is suggested.}, } @article {pmid35681485, year = {2022}, author = {Minelli, A and Valero-Gracia, A}, title = {Spatially and Temporally Distributed Complexity-A Refreshed Framework for the Study of GRN Evolution.}, journal = {Cells}, volume = {11}, number = {11}, pages = {}, pmid = {35681485}, issn = {2073-4409}, mesh = {Animals ; *Gene Regulatory Networks ; Genotype ; Phenotype ; }, abstract = {Irrespective of the heuristic value of interpretations of developmental processes in terms of gene regulatory networks (GRNs), larger-angle views often suffer from: (i) an inadequate understanding of the relationship between genotype and phenotype; (ii) a predominantly zoocentric vision; and (iii) overconfidence in a putatively hierarchical organization of animal body plans. Here, we constructively criticize these assumptions. First, developmental biology is pervaded by adultocentrism, but development is not necessarily egg to adult. Second, during development, many unicells undergo transcriptomic profile transitions that are comparable to those recorded in pluricellular organisms; thus, their study should not be neglected from the GRN perspective. Third, the putatively hierarchical nature of the animal body is mirrored in the GRN logic, but in relating genotype to phenotype, independent assessments of the dynamics of the regulatory machinery and the animal's architecture are required, better served by a combinatorial than by a hierarchical approach. The trade-offs between spatial and temporal aspects of regulation, as well as their evolutionary consequences, are also discussed. Multicellularity may derive from a unicell's sequential phenotypes turned into different but coexisting, spatially arranged cell types. In turn, polyphenism may have been a crucial mechanism involved in the origin of complex life cycles.}, } @article {pmid35678467, year = {2022}, author = {Northey, JJ and Weaver, VM}, title = {Mechanosensitive Steroid Hormone Signaling and Cell Fate.}, journal = {Endocrinology}, volume = {163}, number = {8}, pages = {}, pmid = {35678467}, issn = {1945-7170}, support = {R01 CA222508/CA/NCI NIH HHS/United States ; R35 CA242447/CA/NCI NIH HHS/United States ; R01 CA192914/CA/NCI NIH HHS/United States ; }, mesh = {Cell Differentiation ; Hormones/physiology ; Humans ; *Neoplasms/pathology ; *Receptors, Steroid ; Signal Transduction ; Steroids ; }, abstract = {Mechanical forces collaborate across length scales to coordinate cell fate during development and the dynamic homeostasis of adult tissues. Similarly, steroid hormones interact with their nuclear and nonnuclear receptors to regulate diverse physiological processes necessary for the appropriate development and function of complex multicellular tissues. Aberrant steroid hormone action is associated with tumors originating in hormone-sensitive tissues and its disruption forms the basis of several therapeutic interventions. Prolonged perturbations to mechanical forces may further foster tumor initiation and the evolution of aggressive metastatic disease. Recent evidence suggests that steroid hormone and mechanical signaling intersect to direct cell fate during development and tumor progression. Potential mechanosensitive steroid hormone signaling pathways along with their molecular effectors will be discussed in this context.}, } @article {pmid35673523, year = {2022}, author = {Day, TC and Márquez-Zacarías, P and Bravo, P and Pokhrel, AR and MacGillivray, KA and Ratcliff, WC and Yunker, PJ}, title = {Varied solutions to multicellularity: The biophysical and evolutionary consequences of diverse intercellular bonds.}, journal = {Biophysics reviews}, volume = {3}, number = {2}, pages = {021305}, pmid = {35673523}, issn = {2688-4089}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; R35 GM138354/GM/NIGMS NIH HHS/United States ; }, abstract = {The diversity of multicellular organisms is, in large part, due to the fact that multicellularity has independently evolved many times. Nonetheless, multicellular organisms all share a universal biophysical trait: cells are attached to each other. All mechanisms of cellular attachment belong to one of two broad classes; intercellular bonds are either reformable or they are not. Both classes of multicellular assembly are common in nature, having independently evolved dozens of times. In this review, we detail these varied mechanisms as they exist in multicellular organisms. We also discuss the evolutionary implications of different intercellular attachment mechanisms on nascent multicellular organisms. The type of intercellular bond present during early steps in the transition to multicellularity constrains future evolutionary and biophysical dynamics for the lineage, affecting the origin of multicellular life cycles, cell-cell communication, cellular differentiation, and multicellular morphogenesis. The types of intercellular bonds used by multicellular organisms may thus result in some of the most impactful historical constraints on the evolution of multicellularity.}, } @article {pmid35663204, year = {2022}, author = {Nawabi, AK and Jinfang, S and Abbasi, R and Iqbal, MS and Heyat, MBB and Akhtar, F and Wu, K and Twumasi, BA}, title = {Segmentation of Drug-Treated Cell Image and Mitochondrial-Oxidative Stress Using Deep Convolutional Neural Network.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {5641727}, pmid = {35663204}, issn = {1942-0994}, mesh = {Algorithms ; *Image Processing, Computer-Assisted/methods ; *Neural Networks, Computer ; Oxidative Stress ; }, abstract = {Most multicellular organisms require apoptosis, or programmed cell death, to function properly and survive. On the other hand, morphological and biochemical characteristics of apoptosis have remained remarkably consistent throughout evolution. Apoptosis is thought to have at least three functionally distinct phases: induction, effector, and execution. Recent studies have revealed that reactive oxygen species (ROS) and the oxidative stress could play an essential role in apoptosis. Advanced microscopic imaging techniques allow biologists to acquire an extensive amount of cell images within a matter of minutes which rule out the manual analysis of image data acquisition. The segmentation of cell images is often considered the cornerstone and central problem for image analysis. Currently, the issue of segmentation of mitochondrial cell images via deep learning receives increasing attention. The manual labeling of cell images is time-consuming and challenging to train a pro. As a courtesy method, mitochondrial cell imaging (MCI) is proposed to identify the normal, drug-treated, and diseased cells. Furthermore, cell movement (fission and fusion) is measured to evaluate disease risk. The newly proposed drug-treated, normal, and diseased image segmentation (DNDIS) algorithm can quickly segment mitochondrial cell images without supervision and further segment the highly drug-treated cells in the picture, i.e., normal, diseased, and drug-treated cells. The proposed method is based on the ResNet-50 deep learning algorithm. The dataset consists of 414 images mainly categorised into different sets (drug, diseased, and normal) used microscopically. The proposed automated segmentation method has outperformed and secured high precision (90%, 92%, and 94%); moreover, it also achieves proper training. This study will benefit medicines and diseased cell measurements in medical tests and clinical practices.}, } @article {pmid35662747, year = {2022}, author = {Abumsimir, B and Al-Qaisi, TS and Kasmi, Y}, title = {Rereading the genetic origin of cancer: the puzzle of all eras.}, journal = {Future science OA}, volume = {8}, number = {5}, pages = {FSO799}, pmid = {35662747}, issn = {2056-5623}, } @article {pmid35660859, year = {2022}, author = {Bao, L and Ren, J and Nguyen, M and Slusarczyk, AS and Thole, JM and Martinez, SP and Huang, J and Fujita, T and Running, MP}, title = {The cellular function of ROP GTPase prenylation is important for multicellularity in the moss Physcomitrium patens.}, journal = {Development (Cambridge, England)}, volume = {149}, number = {12}, pages = {}, doi = {10.1242/dev.200279}, pmid = {35660859}, issn = {1477-9129}, mesh = {*Bryopsida/metabolism ; Cell Wall/metabolism ; *GTP Phosphohydrolases/metabolism ; Prenylation ; Signal Transduction ; }, abstract = {A complete picture of how signaling pathways lead to multicellularity is largely unknown. Previously, we generated mutations in a protein prenylation enzyme, GGB, and showed that it is essential for maintaining multicellularity in the moss Physcomitrium patens. Here, we show that ROP GTPases act as downstream factors that are prenylated by GGB and themselves play an important role in the multicellularity of P. patens. We also show that the loss of multicellularity caused by the suppression of GGB or ROP GTPases is due to uncoordinated cell expansion, defects in cell wall integrity and the disturbance of the directional control of cell plate orientation. Expressing prenylatable ROP in the ggb mutant not only rescues multicellularity in protonemata but also results in development of gametophores. Although the prenylation of ROP is important for multicellularity, a higher threshold of active ROP is required for gametophore development. Thus, our results suggest that ROP activation via prenylation by GGB is a key process at both cell and tissue levels, facilitating the developmental transition from one dimension to two dimensions and to three dimensions in P. patens.}, } @article {pmid35659869, year = {2022}, author = {Phillips, JE and Santos, M and Konchwala, M and Xing, C and Pan, D}, title = {Genome editing in the unicellular holozoan Capsaspora owczarzaki suggests a premetazoan role for the Hippo pathway in multicellular morphogenesis.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35659869}, issn = {2050-084X}, mesh = {Animals ; Eukaryota/genetics ; *Evolution, Molecular ; *Gene Editing ; Hippo Signaling Pathway ; Morphogenesis ; }, abstract = {Animal development is mediated by a surprisingly small set of canonical signaling pathways such as Wnt, Hedgehog, TGF-beta, Notch, and Hippo pathways. Although once thought to be present only in animals, recent genome sequencing has revealed components of these pathways in the closest unicellular relatives of animals. These findings raise questions about the ancestral functions of these developmental pathways and their potential role in the emergence of animal multicellularity. Here, we provide the first functional characterization of any of these developmental pathways in unicellular organisms by developing techniques for genetic manipulation in Capsaspora owczarzaki, a close unicellular relative of animals that displays aggregative multicellularity. We then use these tools to characterize the Capsaspora ortholog of the Hippo signaling nuclear effector YAP/TAZ/Yorkie (coYki), a key regulator of tissue size in animals. In contrast to what might be expected based on studies in animals, we show that coYki is dispensable for cell proliferation but regulates cytoskeletal dynamics and the three-dimensional (3D) shape of multicellular structures. We further demonstrate that the cytoskeletal abnormalities of individual coYki mutant cells underlie the abnormal 3D shape of coYki mutant aggregates. Taken together, these findings implicate an ancestral role for the Hippo pathway in cytoskeletal dynamics and multicellular morphogenesis predating the origin of animal multicellularity, which was co-opted during evolution to regulate cell proliferation.}, } @article {pmid35658016, year = {2022}, author = {Bentley, MA and Yates, CA and Hein, J and Preston, GM and Foster, KR}, title = {Pleiotropic constraints promote the evolution of cooperation in cellular groups.}, journal = {PLoS biology}, volume = {20}, number = {6}, pages = {e3001626}, pmid = {35658016}, issn = {1545-7885}, mesh = {*Biological Evolution ; Genotype ; *Microbiota ; Mutation ; Phenotype ; }, abstract = {The evolution of cooperation in cellular groups is threatened by lineages of cheaters that proliferate at the expense of the group. These cell lineages occur within microbial communities, and multicellular organisms in the form of tumours and cancer. In contrast to an earlier study, here we show how the evolution of pleiotropic genetic architectures-which link the expression of cooperative and private traits-can protect against cheater lineages and allow cooperation to evolve. We develop an age-structured model of cellular groups and show that cooperation breaks down more slowly within groups that tie expression to a private trait than in groups that do not. We then show that this results in group selection for pleiotropy, which strongly promotes cooperation by limiting the emergence of cheater lineages. These results predict that pleiotropy will rapidly evolve, so long as groups persist long enough for cheater lineages to threaten cooperation. Our results hold when pleiotropic links can be undermined by mutations, when pleiotropy is itself costly, and in mixed-genotype groups such as those that occur in microbes. Finally, we consider features of multicellular organisms-a germ line and delayed reproductive maturity-and show that pleiotropy is again predicted to be important for maintaining cooperation. The study of cancer in multicellular organisms provides the best evidence for pleiotropic constraints, where abberant cell proliferation is linked to apoptosis, senescence, and terminal differentiation. Alongside development from a single cell, we propose that the evolution of pleiotropic constraints has been critical for cooperation in many cellular groups.}, } @article {pmid35651757, year = {2022}, author = {Díaz, E and Febres, A and Giammarresi, M and Silva, A and Vanegas, O and Gomes, C and Ponte-Sucre, A}, title = {G Protein-Coupled Receptors as Potential Intercellular Communication Mediators in Trypanosomatidae.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {812848}, pmid = {35651757}, issn = {2235-2988}, mesh = {*Calcitonin Gene-Related Peptide/pharmacology ; Cell Communication ; Humans ; *Leishmania/metabolism ; Receptor Activity-Modifying Proteins/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Substance P/pharmacology ; }, abstract = {Detection and transduction of environmental signals, constitute a prerequisite for successful parasite invasion; i.e., Leishmania transmission, survival, pathogenesis and disease manifestation and dissemination, with diverse molecules functioning as inter-cellular signaling ligands. Receptors [i.e., G protein-coupled receptors (GPCRs)] and their associated transduction mechanisms, well conserved through evolution, specialize in this function. However, canonical GPCR-related signal transduction systems have not been described in Leishmania, although orthologs, with reduced domains and function, have been identified in Trypanosomatidae. These inter-cellular communication means seem to be essential for multicellular and unicellular organism's survival. GPCRs are flexible in their molecular architecture and may interact with the so-called receptor activity-modifying proteins (RAMPs), which modulate their function, changing GPCRs pharmacology, acting as chaperones and regulating signaling and/or trafficking in a receptor-dependent manner. In the skin, vasoactive- and neuro- peptides released in response to the noxious stimuli represented by the insect bite may trigger parasite physiological responses, for example, chemotaxis. For instance, in Leishmania (V.) braziliensis, sensory [Substance P, SP, chemoattractant] and autonomic [Vasoactive Intestinal Peptide, VIP, and Neuropeptide Y, NPY, chemorepellent] neuropeptides at physiological levels stimulate in vitro effects on parasite taxis. VIP and NPY chemotactic effects are impaired by their corresponding receptor antagonists, suggesting that the stimulated responses might be mediated by putative GPCRs (with essential conserved receptor domains); the effect of SP is blocked by [(D-Pro 2, D-Trp7,9]-Substance P (10[-6] M)] suggesting that it might be mediated by neurokinin-1 transmembrane receptors. Additionally, vasoactive molecules like Calcitonin Gene-Related Peptide [CGRP] and Adrenomedullin [AM], exert a chemorepellent effect and increase the expression of a 24 kDa band recognized in western blot analysis by (human-)-RAMP-2 antibodies. In-silico search oriented towards GPCRs-like receptors and signaling cascades detected a RAMP-2-aligned sequence corresponding to Leishmania folylpolyglutamate synthase and a RAMP-3 aligned protein, a hypothetical Leishmania protein with yet unknown function, suggesting that in Leishmania, CGRP and AM activities may be modulated by RAMP- (-2) and (-3) homologs. The possible presence of proteins and molecules potentially involved in GPCRs cascades, i.e., RAMPs, signpost conservation of ancient signaling systems associated with responses, fundamental for cell survival, (i.e., taxis and migration) and may constitute an open field for description of pharmacophores against Leishmania parasites.}, } @article {pmid35650214, year = {2022}, author = {Goswami, P and He, K and Li, J and Pan, Y and Roberts, AP and Lin, W}, title = {Magnetotactic bacteria and magnetofossils: ecology, evolution and environmental implications.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {43}, pmid = {35650214}, issn = {2055-5008}, mesh = {Bacteria/genetics ; *Ecosystem ; *Fresh Water ; Prospective Studies ; }, abstract = {Magnetotactic bacteria (MTB) are a group of phylogenetically diverse and morphologically varied microorganisms with a magnetoresponsive capability called magnetotaxis or microbial magnetoreception. MTB are a distinctive constituent of the microbiome of aquatic ecosystems because they use Earth's magnetic field to align themselves in a north or south facing direction and efficiently navigate to their favored microenvironments. They have been identified worldwide from diverse aquatic and waterlogged microbiomes, including freshwater, saline, brackish and marine ecosystems, and some extreme environments. MTB play important roles in the biogeochemical cycling of iron, sulphur, phosphorus, carbon and nitrogen in nature and have been recognized from in vitro cultures to sequester heavy metals like selenium, cadmium, and tellurium, which makes them prospective candidate organisms for aquatic pollution bioremediation. The role of MTB in environmental systems is not limited to their lifespan; after death, fossil magnetosomal magnetic nanoparticles (known as magnetofossils) are a promising proxy for recording paleoenvironmental change and geomagnetic field history. Here, we summarize the ecology, evolution, and environmental function of MTB and the paleoenvironmental implications of magnetofossils in light of recent discoveries.}, } @article {pmid35642429, year = {2022}, author = {Bonforti, A and Solé, R}, title = {Unicellular-multicellular evolutionary branching driven by resource limitations.}, journal = {Journal of the Royal Society, Interface}, volume = {19}, number = {191}, pages = {20220018}, pmid = {35642429}, issn = {1742-5662}, mesh = {*Biological Evolution ; Cell Adhesion ; }, abstract = {Multicellular life forms have evolved many times on our planet, suggesting that this is a common evolutionary innovation. Multiple advantages have been proposed for the emergence of multicellularity (MC). In this paper, we address the problem of how the first precondition for MC, namely 'stay together', might have occurred under spatially limited resources exploited by a population of unicellular agents. Using a minimal model of evolved cell-cell adhesion among growing and dividing cells that exploit a localized resource with a given size, we show that a transition occurs at a critical resource size separating a phase of evolved multicellular aggregates from a phase where unicellularity (UC) is favoured. The two phases are separated by an intermediate domain where both UC and MC can be selected by evolution. This model provides a minimal approach to the early stages that were required to transition from individuality to cohesive groups of cells associated with a physical cooperative effect: when resources are present only in a localized portion of the habitat, MC is a desirable property as it helps cells to keep close to the available local nutrients.}, } @article {pmid35630369, year = {2022}, author = {Cui, K and Pan, H and Chen, J and Liu, J and Zhao, Y and Chen, S and Zhang, W and Xiao, T and Wu, LF}, title = {A Novel Isolate of Spherical Multicellular Magnetotactic Prokaryotes Has Two Magnetosome Gene Clusters and Synthesizes Both Magnetite and Greigite Crystals.}, journal = {Microorganisms}, volume = {10}, number = {5}, pages = {}, pmid = {35630369}, issn = {2076-2607}, support = {42176123//National Natural Science Foundation of China/ ; 2018FY100106//National Specialized Project of Science and Technology/ ; U1706208//National Natural Science Foundation of China, Shandong Joint Fund/ ; }, abstract = {Multicellular magnetotactic prokaryotes (MMPs) are a unique group of magnetotactic bacteria that are composed of 10-100 individual cells and show coordinated swimming along magnetic field lines. MMPs produce nanometer-sized magnetite (Fe3O4) and/or greigite (Fe3S4) crystals-termed magnetosomes. Two types of magnetosome gene cluster (MGC) that regulate biomineralization of magnetite and greigite have been found. Here, we describe a dominant spherical MMP (sMMP) species collected from the intertidal sediments of Jinsha Bay, in the South China Sea. The sMMPs were 4.78 ± 0.67 μm in diameter, comprised 14-40 cells helical symmetrically, and contained bullet-shaped magnetite and irregularly shaped greigite magnetosomes. Two sets of MGCs, one putatively related to magnetite biomineralization and the other to greigite biomineralization, were identified in the genome of the sMMP, and two sets of paralogous proteins (Mam and Mad) that may function separately and independently in magnetosome biomineralization were found. Phylogenetic analysis indicated that the sMMPs were affiliated with Deltaproteobacteria. This is the first direct report of two types of magnetosomes and two sets of MGCs being detected in the same sMMP. The study provides new insights into the mechanism of biomineralization of magnetosomes in MMPs, and the evolutionary origin of MGCs.}, } @article {pmid35628404, year = {2022}, author = {Paradžik, T and Podgorski, II and Vojvoda Zeljko, T and Paradžik, M}, title = {Ancient Origins of Cytoskeletal Crosstalk: Spectraplakin-like Proteins Precede the Emergence of Cortical Microtubule Stabilization Complexes as Crosslinkers.}, journal = {International journal of molecular sciences}, volume = {23}, number = {10}, pages = {}, pmid = {35628404}, issn = {1422-0067}, mesh = {Actin Cytoskeleton/metabolism ; *Actins/metabolism ; Animals ; *Cytoskeleton/metabolism ; Microtubules/metabolism ; Phylogeny ; }, abstract = {Adhesion between cells and the extracellular matrix (ECM) is one of the prerequisites for multicellularity, motility, and tissue specialization. Focal adhesions (FAs) are defined as protein complexes that mediate signals from the ECM to major components of the cytoskeleton (microtubules, actin, and intermediate filaments), and their mutual communication determines a variety of cellular processes. In this study, human cytoskeletal crosstalk proteins were identified by comparing datasets with experimentally determined cytoskeletal proteins. The spectraplakin dystonin was the only protein found in all datasets. Other proteins (FAK, RAC1, septin 9, MISP, and ezrin) were detected at the intersections of FAs, microtubules, and actin cytoskeleton. Homology searches for human crosstalk proteins as queries were performed against a predefined dataset of proteomes. This analysis highlighted the importance of FA communication with the actin and microtubule cytoskeleton, as these crosstalk proteins exhibit the highest degree of evolutionary conservation. Finally, phylogenetic analyses elucidated the early evolutionary history of spectraplakins and cortical microtubule stabilization complexes (CMSCs) as model representatives of the human cytoskeletal crosstalk. While spectraplakins probably arose at the onset of opisthokont evolution, the crosstalk between FAs and microtubules is associated with the emergence of metazoans. The multiprotein complexes contributing to cytoskeletal crosstalk in animals gradually gained in complexity from the onset of metazoan evolution.}, } @article {pmid35626631, year = {2022}, author = {Paul, B and Sterner, ZR and Buchholz, DR and Shi, YB and Sachs, LM}, title = {Thyroid and Corticosteroid Signaling in Amphibian Metamorphosis.}, journal = {Cells}, volume = {11}, number = {10}, pages = {}, pmid = {35626631}, issn = {2073-4409}, mesh = {Adrenal Cortex Hormones ; Amphibians ; Animals ; *Metamorphosis, Biological/physiology ; *Thyroid Gland/metabolism ; Thyroid Hormones/metabolism ; Vertebrates/metabolism ; }, abstract = {In multicellular organisms, development is based in part on the integration of communication systems. Two neuroendocrine axes, the hypothalamic-pituitary-thyroid and the hypothalamic-pituitary-adrenal/interrenal axes, are central players in orchestrating body morphogenesis. In all vertebrates, the hypothalamic-pituitary-thyroid axis controls thyroid hormone production and release, whereas the hypothalamic-pituitary-adrenal/interrenal axis regulates the production and release of corticosteroids. One of the most salient effects of thyroid hormones and corticosteroids in post-embryonic developmental processes is their critical role in metamorphosis in anuran amphibians. Metamorphosis involves modifications to the morphological and biochemical characteristics of all larval tissues to enable the transition from one life stage to the next life stage that coincides with an ecological niche switch. This transition in amphibians is an example of a widespread phenomenon among vertebrates, where thyroid hormones and corticosteroids coordinate a post-embryonic developmental transition. The review addresses the functions and interactions of thyroid hormone and corticosteroid signaling in amphibian development (metamorphosis) as well as the developmental roles of these two pathways in vertebrate evolution.}, } @article {pmid35621103, year = {2022}, author = {Puzakov, MV and Puzakova, LV}, title = {[Prevalence, Diversity, and Evolution of L18 (DD37E) Transposons in the Genomes of Cnidarians].}, journal = {Molekuliarnaia biologiia}, volume = {56}, number = {3}, pages = {476-490}, doi = {10.31857/S0026898422030120}, pmid = {35621103}, issn = {0026-8984}, mesh = {Animals ; *Cnidaria/genetics ; *DNA Transposable Elements/genetics ; Prevalence ; }, abstract = {Transposable elements have a significant impact on the structure and functioning of multicellular genomes, and also serve as a source of new genes. Studying the diversity and evolution of transposable elements in different taxa is necessary for the fundamental understanding of their role in genomes. The Tc1/mariner elements are one of the most widespread and diverse groups of DNA transposons. In this work, the structure, distribution, diversity, and evolution of the L18 (DD37E) elements in the genomes of cnidarians (Cnidaria) were studied for the first time. As a result, it was found that the L18 group is an independent family (and not a subfamily of the TLE family, as previously thought) in the Tc1/mariner superfamily. Of the 51 detected elements, only four had potentially functional copies. It is assumed that the L18 transposons are of ancient origin, and, in addition, the elements found in the genomes of organisms of the Anthozoa and Hydrozoa classes do not come from a common ancestral transposon within the Cnidaria phylum. In organisms of the Hydrozoa class, L18 transposons appeared as a result of horizontal transfer at a later time period. An intraspecies comparison of the diversity of the L18 elements demonstrates high homogeneity with respect to "old" transposons, which have already lost their activity. At the same time, distant populations, as in the case of Hydra viridissima, have differences in the representation of DNA transposons and the number of copies. These data supplement the knowledge on the diversity and evolution of Tc1/mariner transposons and contribute to the study of the influence of mobile genetic elements on the evolution of multicellular organisms.}, } @article {pmid35606056, year = {2022}, author = {Bush, JO}, title = {Cellular and molecular mechanisms of EPH/EPHRIN signaling in evolution and development.}, journal = {Current topics in developmental biology}, volume = {149}, number = {}, pages = {153-201}, doi = {10.1016/bs.ctdb.2022.02.005}, pmid = {35606056}, issn = {1557-8933}, support = {R01 DE023337/DE/NIDCR NIH HHS/United States ; R01 DE025877/DE/NIDCR NIH HHS/United States ; R01 DE028753/DE/NIDCR NIH HHS/United States ; R01 HL144785/HL/NHLBI NIH HHS/United States ; }, mesh = {Cell Adhesion ; *Ephrins/metabolism ; Protein Binding ; *Receptors, Eph Family/metabolism ; Signal Transduction/physiology ; }, abstract = {The EPH receptor tyrosine kinases and their signaling partners, the EPHRINS, comprise a large class of cell signaling molecules that plays diverse roles in development. As cell membrane-anchored signaling molecules, they regulate cellular organization by modulating the strength of cellular contacts, usually by impacting the actin cytoskeleton or cell adhesion programs. Through these cellular functions, EPH/EPHRIN signaling often regulates tissue shape. Indeed, recent evidence indicates that this signaling family is ancient and associated with the origin of multicellularity. Though extensively studied, our understanding of the signaling mechanisms employed by this large family of signaling proteins remains patchwork, and a truly "canonical" EPH/EPHRIN signal transduction pathway is not known and may not exist. Instead, several foundational evolutionarily conserved mechanisms are overlaid by a myriad of tissue -specific functions, though common themes emerge from these as well. Here, I review recent advances and the related contexts that have provided new understanding of the conserved and varied molecular and cellular mechanisms employed by EPH/EPHRIN signaling during development.}, } @article {pmid35588907, year = {2022}, author = {Udayantha, HMV and Samaraweera, AV and Liyanage, DS and Sandamalika, WMG and Lim, C and Yang, H and Lee, JH and Lee, S and Lee, J}, title = {Molecular characterization, antiviral activity, and UV-B damage responses of Caspase-9 from Amphiprion clarkii.}, journal = {Fish & shellfish immunology}, volume = {125}, number = {}, pages = {247-257}, doi = {10.1016/j.fsi.2022.05.023}, pmid = {35588907}, issn = {1095-9947}, mesh = {Animals ; Antiviral Agents ; Caspase 3 ; Caspase 9 ; *Cyprinidae ; *Perciformes ; Phylogeny ; Poly I-C/pharmacology ; }, abstract = {Apoptosis plays a vital role in maintaining cellular homeostasis in multicellular organisms. Caspase-9 (casp-9) is one of the major initiator caspases that induces apoptosis by activating downstream intrinsic apoptosis pathway genes. Here, we isolated the cDNA sequence (1992 bp) of caspase-9 from Amphiprion clarkii (Accasp-9) that consists of a 1305 bp coding region and encodes a 434 aa protein. In silico analysis showed that Accasp-9 has a theoretical isoelectric point of 5.81 and a molecular weight of 48.45 kDa. Multiple sequence alignment revealed that the CARD domain is located at the N-terminus, whereas the large P-20 and small P-10 domains are located at the C-terminus. Moreover, a highly conserved pentapeptide active site ([296]QACGG[301]), as well as histidine and cysteine active sites, are also retained at the C-terminus. In phylogenetic analysis, Accasp-9 formed a clade with casp-9 from different species, distinct from other caspases. Accasp-9 was highly expressed in the gill and intestine compared with other tissues analyzed in healthy A. clarkii. Accasp-9 expression was significantly elevated in the blood after stimulation with Vibrio harveyi and polyinosinic:polycytidylic acid (poly I:C; 12-48 h), but not with lipopolysaccharide. The nucleoprotein expression of the viral hemorrhagic septicemia virus was significantly reduced in Accasp-9 overexpressed fathead minnow (FHM) cells compared with that in the control. In addition, other in vitro assays revealed that cell apoptosis was significantly elevated in poly I:C and UV-B-treated Accasp-9 transfected FHM cells. However, H[248P] or C[298S] mutated Accasp-9 significantly reduced apoptosis in UV-B irradiated cells. Collectively, our results show that Accasp-9 might play a defensive role against invading pathogens and UV-B radiation and H[248] and C[298] active residues are significantly involved in apoptosis in teleosts.}, } @article {pmid35587048, year = {2022}, author = {Gardner, DS and Gray, C}, title = {Development and the art of nutritional maintenance.}, journal = {The British journal of nutrition}, volume = {128}, number = {5}, pages = {828-834}, pmid = {35587048}, issn = {1475-2662}, mesh = {Animals ; Nutritive Value ; *Nutrients ; *Energy Intake ; }, abstract = {Development from early conceptus to a complex, multi-cellular organism is a highly ordered process that is dependent on an adequate supply of nutrients. During this process, the pattern of organ growth is robust, driven by a genetic blueprint and matched to anticipated body mass with high precision and with built-in physiological reserve capacity. This apparent canalisation of the developmental process is particularly sensitive to variation in environmental stimuli, such as inappropriate drug or hormone exposure, or pattern of nutrient delivery. Significant variation in any of these factors can profoundly affect fetal and neonatal growth patterns, with later detriment for physiological function and/or reserve capacity of the resultant adult, with potential health impact. This paradigm shift in science has become known as the Developmental Origins of Health and Disease (DOHaD). Over the last 30 years, many animal and clinical studies have vastly expanded our fundamental knowledge of developmental biology, particularly in the context of later effects on health. In this horizons article, we discuss DOHaD through the lens of nutritional quality (e.g. micronutrient, amino acid, NSP intake). The concept of ‘Quality’ was considered undefinable by Robert Persig in his book, ‘Zen and the Art of Motorcycle Maintenance’. Here, development and the art of nutritional maintenance will define quality in terms of the pattern of nutrient intake, the quality of development and how each interact to influence later health outcomes.}, } @article {pmid35574025, year = {2022}, author = {Ritch, SJ and Telleria, CM}, title = {The Transcoelomic Ecosystem and Epithelial Ovarian Cancer Dissemination.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {886533}, pmid = {35574025}, issn = {1664-2392}, mesh = {Carcinoma, Ovarian Epithelial ; *Ecosystem ; Epithelial Cells/metabolism ; Female ; Humans ; Neoplasm Recurrence, Local ; *Ovarian Neoplasms/therapy ; Tumor Microenvironment ; }, abstract = {Epithelial ovarian cancer (EOC) is considered the deadliest gynecological disease and is normally diagnosed at late stages, at which point metastasis has already occurred. Throughout disease progression, EOC will encounter various ecosystems and the communication between cancer cells and these microenvironments will promote the survival and dissemination of EOC. The primary tumor is thought to develop within the ovaries or the fallopian tubes, both of which provide a microenvironment with high risk of causing DNA damage and enhanced proliferation. EOC disseminates by direct extension from the primary tumors, as single cells or multicellular aggregates. Under the influence of cellular and non-cellular factors, EOC spheroids use the natural flow of peritoneal fluid to reach distant organs within the peritoneal cavity. These cells can then implant and seed distant organs or tissues, which develop rapidly into secondary tumor nodules. The peritoneal tissue and the omentum are two common sites of EOC metastasis, providing a microenvironment that supports EOC invasion and survival. Current treatment for EOC involves debulking surgery followed by platinum-taxane combination chemotherapy; however, most patients will relapse with a chemoresistant disease with tumors developed within the peritoneum. Therefore, understanding the role of the unique microenvironments that promote EOC transcoelomic dissemination is important in improving patient outcomes from this disease. In this review article, we address the process of ovarian cancer cellular fate at the site of its origin in the secretory cells of the fallopian tube or in the ovarian surface epithelial cells, their detachment process, how the cells survive in the peritoneal fluid avoiding cell death triggers, and how cancer- associated cells help them in the process. Finally, we report the mechanisms used by the ovarian cancer cells to adhere and migrate through the mesothelial monolayer lining the peritoneum. We also discuss the involvement of the transcoelomic ecosystem on the development of chemoresistance of EOC.}, } @article {pmid35572413, year = {2022}, author = {Zhang, J and Shen, N and Li, C and Xiang, X and Liu, G and Gui, Y and Patev, S and Hibbett, DS and Barry, K and Andreopoulos, W and Lipzen, A and Riley, R and He, G and Yan, M and Grigoriev, IV and Shan Kwan, H and Kit Cheung, M and Bian, Y and Xiao, Y}, title = {Population genomics provides insights into the genetic basis of adaptive evolution in the mushroom-forming fungus Lentinula edodes.}, journal = {Journal of advanced research}, volume = {38}, number = {}, pages = {91-106}, pmid = {35572413}, issn = {2090-1224}, mesh = {*Agaricales/genetics ; Genome ; Genome-Wide Association Study ; Metagenomics ; *Shiitake Mushrooms/genetics ; }, abstract = {INTRODUCTION: Mushroom-forming fungi comprise diverse species that develop complex multicellular structures. In cultivated species, both ecological adaptation and artificial selection have driven genome evolution. However, little is known about the connections among genotype, phenotype and adaptation in mushroom-forming fungi.

OBJECTIVES: This study aimed to (1) uncover the population structure and demographic history of Lentinula edodes, (2) dissect the genetic basis of adaptive evolution in L. edodes, and (3) determine if genes related to fruiting body development are involved in adaptive evolution.

METHODS: We analyzed genomes and fruiting body-related traits (FBRTs) in 133 L. edodes strains and conducted RNA-seq analysis of fruiting body development in the YS69 strain. Combined methods of genomic scan for divergence, genome-wide association studies (GWAS), and RNA-seq were used to dissect the genetic basis of adaptive evolution.

RESULTS: We detected three distinct subgroups of L. edodes via single nucleotide polymorphisms, which showed robust phenotypic and temperature response differentiation and correlation with geographical distribution. Demographic history inference suggests that the subgroups diverged 36,871 generations ago. Moreover, L. edodes cultivars in China may have originated from the vicinity of Northeast China. A total of 942 genes were found to be related to genetic divergence by genomic scan, and 719 genes were identified to be candidates underlying FBRTs by GWAS. Integrating results of genomic scan and GWAS, 80 genes were detected to be related to phenotypic differentiation. A total of 364 genes related to fruiting body development were involved in genetic divergence and phenotypic differentiation.

CONCLUSION: Adaptation to the local environment, especially temperature, triggered genetic divergence and phenotypic differentiation of L. edodes. A general model for genetic divergence and phenotypic differentiation during adaptive evolution in L. edodes, which involves in signal perception and transduction, transcriptional regulation, and fruiting body morphogenesis, was also integrated here.}, } @article {pmid35570706, year = {2022}, author = {Heinz, MC and Peters, NA and Oost, KC and Lindeboom, RGH and van Voorthuijsen, L and Fumagalli, A and van der Net, MC and de Medeiros, G and Hageman, JH and Verlaan-Klink, I and Borel Rinkes, IHM and Liberali, P and Gloerich, M and van Rheenen, J and Vermeulen, M and Kranenburg, O and Snippert, HJG}, title = {Liver Colonization by Colorectal Cancer Metastases Requires YAP-Controlled Plasticity at the Micrometastatic Stage.}, journal = {Cancer research}, volume = {82}, number = {10}, pages = {1953-1968}, pmid = {35570706}, issn = {1538-7445}, mesh = {Animals ; *Colorectal Neoplasms/pathology ; Humans ; *Liver Neoplasms/metabolism ; Mice ; Neoplasm Micrometastasis/pathology ; Neoplastic Stem Cells/pathology ; }, abstract = {UNLABELLED: Micrometastases of colorectal cancer can remain dormant for years prior to the formation of actively growing, clinically detectable lesions (i.e., colonization). A better understanding of this step in the metastatic cascade could help improve metastasis prevention and treatment. Here we analyzed liver specimens of patients with colorectal cancer and monitored real-time metastasis formation in mouse livers using intravital microscopy to reveal that micrometastatic lesions are devoid of cancer stem cells (CSC). However, lesions that grow into overt metastases demonstrated appearance of de novo CSCs through cellular plasticity at a multicellular stage. Clonal outgrowth of patient-derived colorectal cancer organoids phenocopied the cellular and transcriptomic changes observed during in vivo metastasis formation. First, formation of mature CSCs occurred at a multicellular stage and promoted growth. Conversely, failure of immature CSCs to generate more differentiated cells arrested growth, implying that cellular heterogeneity is required for continuous growth. Second, early-stage YAP activity was required for the survival of organoid-forming cells. However, subsequent attenuation of early-stage YAP activity was essential to allow for the formation of cell type heterogeneity, while persistent YAP signaling locked micro-organoids in a cellularly homogenous and growth-stalled state. Analysis of metastasis formation in mouse livers using single-cell RNA sequencing confirmed the transient presence of early-stage YAP activity, followed by emergence of CSC and non-CSC phenotypes, irrespective of the initial phenotype of the metastatic cell of origin. Thus, establishment of cellular heterogeneity after an initial YAP-controlled outgrowth phase marks the transition to continuously growing macrometastases.

SIGNIFICANCE: Characterization of the cell type dynamics, composition, and transcriptome of early colorectal cancer liver metastases reveals that failure to establish cellular heterogeneity through YAP-controlled epithelial self-organization prohibits the outgrowth of micrometastases. See related commentary by LeBleu, p. 1870.}, } @article {pmid35563757, year = {2022}, author = {Stange, K and Keric, A and Friese, A and Röntgen, M}, title = {Preparation of Spheroids from Primary Pig Cells in a Mid-Scale Bioreactor Retaining Their Myogenic Potential.}, journal = {Cells}, volume = {11}, number = {9}, pages = {}, pmid = {35563757}, issn = {2073-4409}, mesh = {Animals ; Bioreactors ; Cell Differentiation ; *Muscle Development ; *Muscle Fibers, Skeletal ; Swine ; }, abstract = {Three-dimensional cell culture techniques mimic the in vivo cell environment more adequately than flat surfaces. Spheroids are multicellular aggregates and we aimed to produce scaffold-free spheroids of myogenic origin, called myospheres, using a mid-scale incubator and bioreactor hybrid. For the first time, we obtained spheroids from primary porcine muscle cells (PMCs) with this technology and compared their morphology and growth parameters, marker expression, and myogenic potential to C2C12-derived spheroids. Both cell types were able to form round-shaped spheroids in the bioreactor already after 24 h. The mean diameter of the C2C12 spheroids (44.6 µm) was larger than that of the PMCs (32.7 µm), and the maximum diameter exceeded 1 mm. C2C12 cells formed less aggregates than PMCs with a higher packing density (cell nuclei/mm[2]). After dissociation from the spheroids, C2C12 cells and PMCs started to proliferate again and were able to differentiate into the myogenic lineage, as shown by myotube formation and the expression of F-Actin, Desmin, MyoG, and Myosin. For C2C12, multinucleated syncytia and Myosin expression were observed in spheroids, pointing to accelerated myogenic differentiation. In conclusion, the mid-scale incubator and bioreactor system is suitable for spheroid formation and cultivation from primary muscle cells while preserving their myogenic potential.}, } @article {pmid35551578, year = {2022}, author = {Eskandari, E and Eaves, CJ}, title = {Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis.}, journal = {The Journal of cell biology}, volume = {221}, number = {6}, pages = {}, pmid = {35551578}, issn = {1540-8140}, support = {21296//Canadian Cancer Society Research Institute/ ; //University of British Columbia/ ; }, mesh = {Apoptosis/genetics ; *Carcinogenesis/genetics ; *Caspase 3/physiology ; *Cell Proliferation ; *Cell Survival/genetics ; Humans ; Saccharomyces cerevisiae ; }, abstract = {Caspase-3 is a widely expressed member of a conserved family of proteins, generally recognized for their activated proteolytic roles in the execution of apoptosis in cells responding to specific extrinsic or intrinsic inducers of this mode of cell death. However, accumulating evidence indicates that caspase-3 also plays key roles in regulating the growth and homeostatic maintenance of both normal and malignant cells and tissues in multicellular organisms. Given that yeast possess an ancestral caspase-like gene suggests that the caspase-3 protein may have acquired different functions later during evolution to better meet the needs of more complex multicellular organisms, but without necessarily losing all of the functions of its ancestral yeast precursor. This review provides an update on what has been learned about these interesting dichotomous roles of caspase-3, their evolution, and their potential relevance to malignant as well as normal cell biology.}, } @article {pmid35530508, year = {2022}, author = {de la Fuente, M and Novo, M}, title = {Understanding Diversity, Evolution, and Structure of Small Heat Shock Proteins in Annelida Through in Silico Analyses.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {817272}, pmid = {35530508}, issn = {1664-042X}, abstract = {Small heat shock proteins (sHsps) are oligomeric stress proteins characterized by an α-crystallin domain (ACD). These proteins are localized in different subcellular compartments and play critical roles in the stress physiology of tissues, organs, and whole multicellular eukaryotes. They are ubiquitous proteins found in all living organisms, from bacteria to mammals, but they have never been studied in annelids. Here, a data set of 23 species spanning the annelid tree of life, including mostly transcriptomes but also two genomes, was interrogated and 228 novel putative sHsps were identified and manually curated. The analysis revealed very high protein diversity and showed that a significant number of sHsps have a particular dimeric architecture consisting of two tandemly repeated ACDs. The phylogenetic analysis distinguished three main clusters, two of them containing both monomeric sHsps, and ACDs located downstream in the dimeric sHsps, and the other one comprising the upstream ACDs from those dimeric forms. Our results support an evolutionary history of these proteins based on duplication events prior to the Spiralia split. Monomeric sHsps 76) were further divided into five subclusters. Physicochemical properties, subcellular location predictions, and sequence conservation analyses provided insights into the differentiating elements of these putative functional groups. Strikingly, three of those subclusters included sHsps with features typical of metazoans, while the other two presented characteristics resembling non-metazoan proteins. This study provides a solid background for further research on the diversity, evolution, and function in the family of the sHsps. The characterized annelid sHsps are disclosed as essential for improving our understanding of this important family of proteins and their pleotropic functions. The features and the great diversity of annelid sHsps position them as potential powerful molecular biomarkers of environmental stress for acting as prognostic tool in a diverse range of environments.}, } @article {pmid35526729, year = {2022}, author = {Nakajima, T}, title = {Computation by inverse causality: A universal principle to produce symbols for the external reality in living systems.}, journal = {Bio Systems}, volume = {218}, number = {}, pages = {104692}, doi = {10.1016/j.biosystems.2022.104692}, pmid = {35526729}, issn = {1872-8324}, mesh = {*Adaptation, Physiological ; Causality ; *Philosophy ; Probability ; }, abstract = {How can a living system escape the solipsistic self-making process? This problem has been ignored in mainstream biology. This study seeks a reasonable mechanism by which a living system produces symbols that signify external states. To this end, the inverse causality model proposed in previous studies was theoretically improved by refining the core concepts. Inverse causality is an epistemic principle operating in a subject system to produce symbols internally, signifying the past states of the external reality hidden to the subject. Inverse causality yields an important theorem for a system to produce symbols for external states. It asserts that if a system changes from state x to y1 in some instances, and from x to y2 in others (y1 ≠ y2), then x ⟼ y1 produces a symbol that signifies one external state, and x ⟼ y2 produces a different symbol for another state. These symbols are embodied as the states of the system components. The model postulates the equivalence principle in the subject-reality relationship, asserting that inverse causality is equivalent to causality in the external view. Living systems operate with inverse causality using biological devices called measurers, which include membrane receptors, second messengers, and molecular switches in cells, and neurons in multicellular organisms. A measurer is a medium of symbols signifying external states. Biological subsystems functioning as measurers are ubiquitous and essential in contemporary living systems for adaptation to their environments in particular ways by manipulating the symbols they produce. By the inverse causality operation, living systems can reduce the uncertainty of events and manage the probability distribution of future events favorable to survival and reproduction. Due to this function, their measurer systems were sophisticated and diversified in evolution. In philosophy and science, there has been endless debate between determinism and indeterminism. However, surprisingly, contemporary living systems use the inverse causality operation (ICW) to adapt to their environments, which is logically equivalent to the causal principle of determinism.}, } @article {pmid35514085, year = {2022}, author = {Yuan, F and Wang, X and Zhao, B and Xu, X and Shi, M and Leng, B and Dong, X and Lu, C and Feng, Z and Guo, J and Han, G and Zhang, H and Huang, J and Chen, M and Wang, BS}, title = {The genome of the recretohalophyte Limonium bicolor provides insights into salt gland development and salinity adaptation during terrestrial evolution.}, journal = {Molecular plant}, volume = {15}, number = {6}, pages = {1024-1044}, doi = {10.1016/j.molp.2022.04.011}, pmid = {35514085}, issn = {1752-9867}, mesh = {Animals ; *Arabidopsis ; Plant Leaves/genetics ; *Plumbaginaceae/genetics ; Salinity ; Salt Gland ; Salt Tolerance/genetics ; Salt-Tolerant Plants/genetics ; }, abstract = {Halophytes have evolved specialized strategies to cope with high salinity. The extreme halophyte sea lavender (Limonium bicolor) lacks trichomes but possesses salt glands on its epidermis that can excrete harmful ions, such as sodium, to avoid salt damage. Here, we report a high-quality, 2.92-Gb, chromosome-scale L. bicolor genome assembly based on a combination of Illumina short reads, single-molecule, real-time long reads, chromosome conformation capture (Hi-C) data, and Bionano genome maps, greatly enriching the genomic information on recretohalophytes with multicellular salt glands. Although the L. bicolor genome contains genes that show similarity to trichome fate genes from Arabidopsis thaliana, it lacks homologs of the decision fate genes GLABRA3, ENHANCER OF GLABRA3, GLABRA2, TRANSPARENT TESTA GLABRA2, and SIAMESE, providing a molecular explanation for the absence of trichomes in this species. We identified key genes (LbHLH and LbTTG1) controlling salt gland development among classical trichome homologous genes and confirmed their roles by showing that their mutations markedly disrupted salt gland initiation, salt secretion, and salt tolerance, thus offering genetic support for the long-standing hypothesis that salt glands and trichomes may share a common origin. In addition, a whole-genome duplication event occurred in the L. bicolor genome after its divergence from Tartary buckwheat and may have contributed to its adaptation to high salinity. The L. bicolor genome resource and genetic evidence reported in this study provide profound insights into plant salt tolerance mechanisms that may facilitate the engineering of salt-tolerant crops.}, } @article {pmid35504284, year = {2022}, author = {Reyes-Rivera, J and Wu, Y and Guthrie, BGH and Marletta, MA and King, N and Brunet, T}, title = {Nitric oxide signaling controls collective contractions in a colonial choanoflagellate.}, journal = {Current biology : CB}, volume = {32}, number = {11}, pages = {2539-2547.e5}, doi = {10.1016/j.cub.2022.04.017}, pmid = {35504284}, issn = {1879-0445}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 GM127854/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Choanoflagellata/metabolism ; Cyclic GMP/metabolism ; Guanylate Cyclase/genetics ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/genetics/metabolism ; Signal Transduction/physiology ; }, abstract = {Although signaling by the gaseous molecule nitric oxide (NO) regulates key physiological processes in animals, including contractility,[1-3] immunity,[4][,][5] development,[6-9] and locomotion,[10][,][11] the early evolution of animal NO signaling remains unclear. To reconstruct the role of NO in the animal stem lineage, we set out to study NO signaling in choanoflagellates, the closest living relatives of animals.[12] In animals, NO produced by the nitric oxide synthase (NOS) canonically signals through cGMP by activating soluble guanylate cyclases (sGCs).[13][,][14] We surveyed the distribution of the NO signaling pathway components across the diversity of choanoflagellates and found three species that express NOS (of either bacterial or eukaryotic origin), sGCs, and downstream genes previously shown to be involved in the NO/cGMP pathway. One of the species coexpressing sGCs and a bacterial-type NOS, Choanoeca flexa, forms multicellular sheets that undergo collective contractions controlled by cGMP.[15] We found that treatment with NO induces cGMP synthesis and contraction in C. flexa. Biochemical assays show that NO directly binds C. flexa sGC1 and stimulates its cyclase activity. The NO/cGMP pathway acts independently from other inducers of C. flexa contraction, including mechanical stimuli and heat, but sGC activity is required for contractions induced by light-to-dark transitions. The output of NO signaling in C. flexa-contractions resulting in a switch from feeding to swimming-resembles the effect of NO in sponges[1-3] and cnidarians,[11][,][16][,][17] where it interrupts feeding and activates contractility. These data provide insights into the biology of the first animals and the evolution of NO signaling.}, } @article {pmid35486699, year = {2022}, author = {Staps, M and Tarnita, CE}, title = {When being flexible matters: Ecological underpinnings for the evolution of collective flexibility and task allocation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {18}, pages = {e2116066119}, pmid = {35486699}, issn = {1091-6490}, mesh = {Animals ; Ants ; *Behavior, Animal ; *Biological Evolution ; Ecology ; Humans ; *Social Behavior ; }, abstract = {Task allocation is a central feature of collective organization. Living collective systems, such as multicellular organisms or social insect colonies, have evolved diverse ways to allocate individuals to different tasks, ranging from rigid, inflexible task allocation that is not adjusted to changing circumstances to more fluid, flexible task allocation that is rapidly adjusted to the external environment. While the mechanisms underlying task allocation have been intensely studied, it remains poorly understood whether differences in the flexibility of task allocation can be viewed as adaptive responses to different ecological contexts—for example, different degrees of temporal variability. Motivated by this question, we develop an analytically tractable mathematical framework to explore the evolution of task allocation in dynamic environments. We find that collective flexibility is not necessarily always adaptive, and fails to evolve in environments that change too slowly (relative to how long tasks can be left unattended) or too quickly (relative to how rapidly task allocation can be adjusted). We further employ the framework to investigate how environmental variability impacts the internal organization of task allocation, which allows us to propose adaptive explanations for some puzzling empirical observations, such as seemingly unnecessary task switching under constant environmental conditions, apparent task specialization without efficiency benefits, and high levels of individual inactivity. Altogether, this work provides a general framework for probing the evolved diversity of task allocation strategies in nature and reinforces the idea that considering a system’s ecology is crucial to explaining its collective organization.}, } @article {pmid35484223, year = {2022}, author = {Goymer, P}, title = {Multicellularity gets real.}, journal = {Nature ecology & evolution}, volume = {6}, number = {6}, pages = {666}, doi = {10.1038/s41559-022-01765-4}, pmid = {35484223}, issn = {2397-334X}, mesh = {*Biological Evolution ; Phylogeny ; }, } @article {pmid35484218, year = {2022}, author = {Farkas, Z and Kovács, K and Sarkadi, Z and Kalapis, D and Fekete, G and Birtyik, F and Ayaydin, F and Molnár, C and Horváth, P and Pál, C and Papp, B}, title = {Gene loss and compensatory evolution promotes the emergence of morphological novelties in budding yeast.}, journal = {Nature ecology & evolution}, volume = {6}, number = {6}, pages = {763-773}, pmid = {35484218}, issn = {2397-334X}, support = {098016/Z/11/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Mutation ; Phenotype ; Saccharomyces cerevisiae/genetics ; *Saccharomycetales/genetics ; }, abstract = {Deleterious mutations are generally considered to be irrelevant for morphological evolution. However, they could be compensated by conditionally beneficial mutations, thereby providing access to new adaptive paths. Here we use high-dimensional phenotyping of laboratory-evolved budding yeast lineages to demonstrate that new cellular morphologies emerge exceptionally rapidly as a by-product of gene loss and subsequent compensatory evolution. Unexpectedly, the capacities for invasive growth, multicellular aggregation and biofilm formation also spontaneously evolve in response to gene loss. These multicellular phenotypes can be achieved by diverse mutational routes and without reactivating the canonical regulatory pathways. These ecologically and clinically relevant traits originate as pleiotropic side effects of compensatory evolution and have no obvious utility in the laboratory environment. The extent of morphological diversity in the evolved lineages is comparable to that of natural yeast isolates with diverse genetic backgrounds and lifestyles. Finally, we show that both the initial gene loss and subsequent compensatory mutations contribute to new morphologies, with their synergistic effects underlying specific morphological changes. We conclude that compensatory evolution is a previously unrecognized source of morphological diversity and phenotypic novelties.}, } @article {pmid35483597, year = {2022}, author = {Wang, B and Zhu, F and Shi, Z and Huang, Z and Sun, R and Wang, Q and Ouyang, G and Ji, W}, title = {Molecular characteristics, polymorphism and expression analysis of mhc Ⅱ in yellow catfish(pelteobagrus fulvidraco)responding to Flavobacterium columnare infection.}, journal = {Fish & shellfish immunology}, volume = {125}, number = {}, pages = {90-100}, doi = {10.1016/j.fsi.2022.04.036}, pmid = {35483597}, issn = {1095-9947}, mesh = {Animals ; *Catfishes ; Fish Proteins/chemistry ; Flavobacterium/genetics ; Phylogeny ; RNA, Messenger/metabolism ; }, abstract = {The major histocompatibility complex (MHC) is an important component of the immune system of vertebrates, which plays a vital role in presenting extrinsic antigens. In this study, we cloned and characterized the mhc ⅡA and mhc ⅡB genes of yellow catfish Pelteobagrus fulvidraco. The open reading frames (ORFs) of mhc ⅡA and mhc ⅡB genes were 708 bp and 747bp in length, encoding 235 and 248 amino acids, respectively. The structure of mhc ⅡA and mhc ⅡB includes a signal peptide, an α1/β1 domain, an α2/β2 domain, a transmembrane region and a cytoplasmic region. Homologous identity analysis revealed that both mhc ⅡA and mhc ⅡB shared high protein sequence similarity with that of Chinese longsnout catfish Leiocassis longirostris. mhc ⅡA and mhc ⅡB showed similar expression patterns in different tissues, with the higher expression level in spleen, head kidney and gill and lower expression in liver, stomach, gall bladder and heart. The mRNA expression level of mhc ⅡA and mhc ⅡB in different embryonic development stages also showed the similar trends. The higher expression was detected from fertilized egg to 32 cell stage, low expression from multicellular period to 3 days post hatching (dph), and then the expression increased to a higher level from 4 dph to 14 dph. The mRNA expression levels of mhc ⅡA and mhc ⅡB were significantly up-regulated not only in the body kidney and spleen, but also in the midgut, hindgut, liver and gill after challenge of Flavobacterium columnare. The results suggest that Mhc Ⅱ plays an important role in the anti-infection process of yellow catfish P. fulvidraco.}, } @article {pmid35477578, year = {2022}, author = {Zhang, Z and Shitut, S and Claushuis, B and Claessen, D and Rozen, DE}, title = {Mutational meltdown of putative microbial altruists in Streptomyces coelicolor colonies.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {2266}, pmid = {35477578}, issn = {2041-1723}, mesh = {Diploidy ; Mutation ; Point Mutation ; Spores, Bacterial/genetics ; *Streptomyces coelicolor/genetics ; }, abstract = {In colonies of the filamentous multicellular bacterium Streptomyces coelicolor, a subpopulation of cells arises that hyperproduces metabolically costly antibiotics, resulting in a division of labor that increases colony fitness. Because these cells contain large genomic deletions that cause massive reductions to individual fitness, their behavior is similar to altruistic worker castes in social insects or somatic cells in multicellular organisms. To understand these mutant cells' reproductive and genomic fate after their emergence, we use experimental evolution by serially transferring populations via spore-to-spore transfer for 25 cycles, reflective of the natural mode of bottlenecked transmission for these spore-forming bacteria. We show that in contrast to wild-type cells, putatively altruistic mutant cells continue to decline in fitness during transfer while they lose more fragments from their chromosome ends. In addition, the base-substitution rate in mutants increases roughly 10-fold, possibly due to mutations in genes for DNA replication and repair. Ecological damage, caused by reduced sporulation, coupled with DNA damage due to point mutations and deletions, leads to an inevitable and irreversible type of mutational meltdown in these cells. Taken together, these results suggest the cells arising in the S. coelicolor division of labor are analogous to altruistic reproductively sterile castes of social insects.}, } @article {pmid35472432, year = {2022}, author = {Chaigne, A and Brunet, T}, title = {Incomplete abscission and cytoplasmic bridges in the evolution of eukaryotic multicellularity.}, journal = {Current biology : CB}, volume = {32}, number = {8}, pages = {R385-R397}, doi = {10.1016/j.cub.2022.03.021}, pmid = {35472432}, issn = {1879-0445}, support = {201334/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Biological Evolution ; Cytoplasm ; Cytosol ; *Eukaryota ; Eukaryotic Cells ; }, abstract = {The textbook view of cell division terminates with the final separation of the two daughter cells in the process called abscission. However, in contrast to this classical view, a variety of cell types in multicellular organisms are connected through cytoplasmic bridges, which most often form by incomplete abscission or - more rarely - by local fusion of plasma membranes. In this review, we survey the distribution, function, and formation of cytoplasmic bridges across the eukaryotic tree of life. We find that cytoplasmic bridges are widespread, and were likely ancestrally present, in almost all lineages of eukaryotes with clonal multicellularity - including the five 'complex multicellular' lineages: animals, fungi, land plants, red algae, and brown algae. In animals, cytoplasmic bridges resulting from incomplete abscission are ubiquitous in the germline and common in pluripotent cell types. Although cytoplasmic bridges have been less studied than other structural mediators of multicellularity (such as adhesion proteins and extracellular matrix), we propose that they have played a pivotal role in the repeated evolution of eukaryotic clonal multicellularity - possibly by first performing a structural role and later by allowing exchange of nutrients and/or intercellular communication, which notably buffered cell-cell competition by averaging gene expression. Bridges were eventually lost from many animal tissues in concert with the evolution of spatial cell differentiation, cell motility within the organism, and other mechanisms for intercellular distribution of signals and metabolites. Finally, we discuss the molecular basis for the evolution of incomplete abscission and examine the alternative hypotheses of single or multiple origins.}, } @article {pmid35470227, year = {2022}, author = {Mulcahey, PJ and Chen, Y and Driscoll, N and Murphy, BB and Dickens, OO and Johnson, ATC and Vitale, F and Takano, H}, title = {Multimodal, Multiscale Insights into Hippocampal Seizures Enabled by Transparent, Graphene-Based Microelectrode Arrays.}, journal = {eNeuro}, volume = {9}, number = {3}, pages = {}, pmid = {35470227}, issn = {2373-2822}, support = {R21 NS106434/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Epilepsy, Temporal Lobe ; *Graphite ; Hippocampus ; Mice ; Microelectrodes ; Seizures ; }, abstract = {Hippocampal seizures are a defining feature of mesial temporal lobe epilepsy (MTLE). Area CA1 of the hippocampus is commonly implicated in the generation of seizures, which may occur because of the activity of endogenous cell populations or of inputs from other regions within the hippocampal formation. Simultaneously observing activity at the cellular and network scales in vivo remains challenging. Here, we present a novel technology for simultaneous electrophysiology and multicellular calcium imaging of CA1 pyramidal cells (PCs) in mice enabled by a transparent graphene-based microelectrode array (Gr MEA). We examine PC firing at seizure onset, oscillatory coupling, and the dynamics of the seizure traveling wave as seizures evolve. Finally, we couple features derived from both modalities to predict the speed of the traveling wave using bootstrap aggregated regression trees. Analysis of the most important features in the regression trees suggests a transition among states in the evolution of hippocampal seizures.}, } @article {pmid35468249, year = {2022}, author = {Melnikov, NP and Bolshakov, FV and Frolova, VS and Skorentseva, KV and Ereskovsky, AV and Saidova, AA and Lavrov, AI}, title = {Tissue homeostasis in sponges: Quantitative analysis of cell proliferation and apoptosis.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {338}, number = {6}, pages = {360-381}, doi = {10.1002/jez.b.23138}, pmid = {35468249}, issn = {1552-5015}, support = {19-04-00545//Russian Foundation for Basic Research/ ; 19-04-00563//Russian Foundation for Basic Research/ ; MK-1096.2021.1.4//Fund of President of the Russian Federation/ ; 17-14-01089//Russian Science Foundation/ ; }, mesh = {Animals ; *Apoptosis ; Cell Proliferation ; Homeostasis ; *Signal Transduction ; }, abstract = {Tissues of multicellular animals are maintained due to a tight balance between cell proliferation and programmed cell death. Sponges are early branching metazoans essential to understanding the key mechanisms of tissue homeostasis. This article is dedicated to the comparative analysis of proliferation and apoptosis in intact tissues of two sponges, Halisarca dujardinii (class Demospongiae) and Leucosolenia variabilis (class Calcarea). Labeled nucleotides EdU and anti-phosphorylated histone 3 antibodies reveal a considerable number of cycling cells in intact tissues of both species. Quantitative DNA staining reveals the classic cell cycle distribution curve. The main type of cycling cells are choanocytes - flagellated cells of the aquiferous system. The rate of proliferation remains constant throughout various areas of sponge bodies that contain choanocytes. The EdU tracking experiments conducted in H. dujardinii indicate that choanocytes may give rise to mesohyl cells through migration. The number of apoptotic cells in tissues of both species is insignificant, although being comparable to the renewing tissues of other animals. In vivo studies with tetramethylrhodamine ethyl ester and CellEvent Caspase-3/7 indicate that apoptosis might be independent of mitochondrial outer membrane permeabilization. Altogether, a combination of confocal laser scanning microscopy and flow cytometry provides a quantitative description of cell proliferation and apoptosis in sponges displaying either rapid growth or cell turnover.}, } @article {pmid35446582, year = {2022}, author = {Gates, C and Ananyev, G and Roy-Chowdhury, S and Cullinane, B and Miller, M and Fromme, P and Dismukes, GC}, title = {Why Did Nature Choose Manganese over Cobalt to Make Oxygen Photosynthetically on the Earth?.}, journal = {The journal of physical chemistry. B}, volume = {126}, number = {17}, pages = {3257-3268}, doi = {10.1021/acs.jpcb.2c00749}, pmid = {35446582}, issn = {1520-5207}, mesh = {Cobalt ; *Cyanobacteria/metabolism ; Manganese/chemistry ; Oxidation-Reduction ; Oxygen/chemistry ; *Photosystem II Protein Complex/chemistry ; Water/chemistry ; }, abstract = {All contemporary oxygenic phototrophs─from primitive cyanobacteria to complex multicellular plants─split water using a single invariant cluster comprising Mn4CaO5 (the water oxidation catalyst) as the catalyst within photosystem II, the universal oxygenic reaction center of natural photosynthesis. This cluster is unstable outside of PSII and can be reconstituted, both in vivo and in vitro, using elemental aqueous ions and light, via photoassembly. Here, we demonstrate the first functional substitution of manganese in any oxygenic reaction center by in vitro photoassembly. Following complete removal of inorganic cofactors from cyanobacterial photosystem II microcrystal (PSIIX), photoassembly with free cobalt (Co[2+]), calcium (Ca[2+]), and water (OH[-]) restores O2 evolution activity. Photoassembly occurs at least threefold faster using Co[2+] versus Mn[2+] due to a higher quantum yield for PSIIX-mediated charge separation (P*): Co[2+] → P* → Co[3+]QA[-]. However, this kinetic preference for Co[2+] over native Mn[2+] during photoassembly is offset by significantly poorer catalytic activity (∼25% of the activity with Mn[2+]) and ∼3- to 30-fold faster photoinactivation rate. The resulting reconstituted Co-PSIIX oxidizes water by the standard four-flash photocycle, although they produce 4-fold less O2 per PSII, suggested to arise from faster charge recombination (Co[3+]QA ← Co[4+]QA[-]) in the catalytic cycle. The faster photoinactivation of reconstituted Co-PSIIX occurs under anaerobic conditions during the catalytic cycle, suggesting direct photodamage without the involvement of O2. Manganese offers two advantages for oxygenic phototrophs, which may explain its exclusive retention throughout Darwinian evolution: significantly slower charge recombination (Mn[3+]QA ← Mn[4+]QA[-]) permits more water oxidation at low and fluctuating solar irradiation (greater net energy conversion) and much greater tolerance to photodamage at high light intensities (Mn[4+] is less oxidizing than Co[4+]). Future work to identify the chemical nature of the intermediates will be needed for further interpretation.}, } @article {pmid35444563, year = {2022}, author = {Mendez-Romero, O and Ricardez-García, C and Castañeda-Tamez, P and Chiquete-Félix, N and Uribe-Carvajal, S}, title = {Thriving in Oxygen While Preventing ROS Overproduction: No Two Systems Are Created Equal.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {874321}, pmid = {35444563}, issn = {1664-042X}, abstract = {From 2.5 to 2.0 billion years ago, atmospheric oxygen concentration [O2] rose thousands of times, leading to the first mass extinction. Reactive Oxygen Species (ROS) produced by the non-catalyzed partial reduction of O2 were highly toxic eliminating many species. Survivors developed different strategies to cope with ROS toxicity. At the same time, using O2 as the final acceptor in respiratory chains increased ATP production manifold. Thus, both O2 and ROS were strong drivers of evolution, as species optimized aerobic metabolism while developing ROS-neutralizing mechanisms. The first line of defense is preventing ROS overproduction and two mechanisms were developed in parallel: 1) Physiological uncoupling systems (PUS), which increase the rate of electron fluxes in respiratory systems. 2) Avoidance of excess [O2]. However, it seems that as avoidance efficiency improved, PUSs became less efficient. PUS includes branched respiratory chains and proton sinks, which may be proton specific, the mitochondrial uncoupling proteins (UCPs) or unspecific, the mitochondrial permeability transition pore (PTP). High [O2] avoidance also involved different strategies: 1) Cell association, as in biofilms or in multi-cellularity allowed gas-permeable organisms (oxyconformers) from bacterial to arthropods to exclude O2. 2) Motility, to migrate from hypoxic niches. 3) Oxyregulator organisms: as early as in fish, and O2-impermeable epithelium excluded all gases and only exact amounts entered through specialized respiratory systems. Here we follow the parallel evolution of PUS and O2-avoidance, PUS became less critical and lost efficiency. In regard, to proton sinks, there is fewer evidence on their evolution, although UCPs have indeed drifted in function while in some species it is not clear whether PTPs exist.}, } @article {pmid35421922, year = {2022}, author = {Nozaki, H and Mori, F and Tanaka, Y and Matsuzaki, R and Yamaguchi, H and Kawachi, M}, title = {Cryopreservation of vegetative cells and zygotes of the multicellular volvocine green alga Gonium pectorale.}, journal = {BMC microbiology}, volume = {22}, number = {1}, pages = {103}, pmid = {35421922}, issn = {1471-2180}, mesh = {*Chlorophyta ; Cryopreservation ; Nitrogen ; Phylogeny ; *Zygote ; }, abstract = {BACKGROUND: Colonial and multicellular volvocine green algae have been extensively studied recently in various fields of the biological sciences. However, only one species (Pandorina morum) has been cryopreserved in public culture collections.

RESULTS: Here, we investigated conditions for cryopreservation of the multicellular volvocine alga Gonium pectorale using vegetative colonies or cells and zygotes. Rates of vegetative cell survival in a G. pectorale strain after two-step cooling and freezing in liquid nitrogen were compared between different concentrations (3% and 6%) of the cryoprotectant N,N-dimethylformamide (DMF) and two types of tubes (0.2-mL polymerase chain reaction tubes and 2-mL cryotubes) used for cryopreservation. Among the four conditions investigated, the highest rate of survival [2.7 ± 3.6% (0.54-10%) by the most probable number (MPN) method] was obtained when 2.0-mL cryotubes containing 1.0 mL of culture samples with 6% DMF were subjected to cryogenic treatment. Using these optimized cryopreservation conditions, survival rates after freezing in liquid nitrogen were examined for twelve other strains of G. pectorale and twelve strains of five other Gonium species. We obtained ≥ 0.1% MPN survival in nine of the twelve G. pectorale strains tested. However, < 0.1% MPN survival was detected in eleven of twelve strains of five other Gonium species. In total, ten cryopreserved strains of G. pectorale were newly established in the Microbial Culture Collection at the National Institute for Environmental Studies. Although the cryopreservation of zygotes of volvocine algae has not been previously reported, high rates (approximately 60%) of G. pectorale zygote germination were observed after thawing zygotes that had been cryopreserved with 5% or 10% methanol as the cryoprotectant during two-step cooling and freezing in liquid nitrogen.

CONCLUSIONS: The present study demonstrated that cryopreservation of G. pectorale is possible with 6% DMF as a cryoprotectant and 1.0-mL culture samples in 2.0-mL cryotubes subjected to two-step cooling in a programmable freezer.}, } @article {pmid35420439, year = {2022}, author = {Rohkin Shalom, S and Weiss, B and Lalzar, M and Kaltenpoth, M and Chiel, E}, title = {Abundance and Localization of Symbiotic Bacterial Communities in the Fly Parasitoid Spalangia cameroni.}, journal = {Applied and environmental microbiology}, volume = {88}, number = {9}, pages = {e0254921}, pmid = {35420439}, issn = {1098-5336}, mesh = {Animals ; Enterobacteriaceae/genetics ; Female ; *Gammaproteobacteria ; In Situ Hybridization, Fluorescence ; Male ; *Rickettsia/genetics ; Symbiosis/physiology ; *Wasps/microbiology ; *Wolbachia/physiology ; }, abstract = {Multicellular eukaryotes often host multiple microbial symbionts that may cooperate or compete for host resources, such as space and nutrients. Here, we studied the abundances and localization of four bacterial symbionts, Rickettsia, Wolbachia, Sodalis, and Arsenophonus, in the parasitic wasp Spalangia cameroni. Using quantitative PCR (qPCR), we measured the symbionts' titers in wasps that harbor different combinations of these symbionts. We found that the titer of each symbiont decreased as the number of symbiont species in the community increased. Symbionts' titers were higher in females than in males. Rickettsia was the most abundant symbiont in all the communities, followed by Sodalis and Wolbachia. The titers of these three symbionts were positively correlated in some of the colonies. Fluorescence in situ hybridization was in line with the qPCR results: Rickettsia, Wolbachia, and Sodalis were observed in high densities in multiple organs, including brain, muscles, gut, Malpighian tubules, fat body, ovaries, and testes, while Arsenophonus was localized to fewer organs and in lower densities. Sodalis and Arsenophonus were observed in ovarian follicle cells but not within oocytes or laid eggs. This study highlights the connection between symbionts' abundance and localization. We discuss the possible connections between our findings to symbiont transmission success. IMPORTANCE Many insects carry intracellular bacterial symbionts (bacteria that reside within the cells of the insect). When multiple symbiont species cohabit in a host, they may compete or cooperate for space, nutrients, and transmission, and the nature of such interactions would be reflected in the abundance of each symbiont species. Given the widespread occurrence of coinfections with maternally transmitted symbionts in insects, it is important to learn more about how they interact, where they are localized, and how these two aspects affect their co-occurrence within individual insects. Here, we studied the abundance and the localization of four symbionts, Rickettsia, Wolbachia, Sodalis, and Arsenophonus, that cohabit the parasitic wasp Spalangia cameroni. We found that symbionts' titers differed between symbiotic communities. These results were corroborated by microscopy, which shows differential localization patterns. We discuss the findings in the contexts of community ecology, possible symbiont-symbiont interactions, and host control mechanisms that may shape the symbiotic community structure.}, } @article {pmid35418164, year = {2022}, author = {Lin, Y and Xu, X and Maróti, G and Strube, ML and Kovács, ÁT}, title = {Adaptation and phenotypic diversification of Bacillus thuringiensis biofilm are accompanied by fuzzy spreader morphotypes.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {27}, pmid = {35418164}, issn = {2055-5008}, mesh = {Bacillus cereus ; *Bacillus thuringiensis/genetics ; Biofilms ; DNA Transposable Elements ; }, abstract = {Bacillus cereus group (Bacillus cereus sensu lato) has a diverse ecology, including various species that produce biofilms on abiotic and biotic surfaces. While genetic and morphological diversification enables the adaptation of multicellular communities, this area remains largely unknown in the Bacillus cereus group. In this work, we dissected the experimental evolution of Bacillus thuringiensis 407 Cry- during continuous recolonization of plastic beads. We observed the evolution of a distinct colony morphotype that we named fuzzy spreader (FS) variant. Most multicellular traits of the FS variant displayed higher competitive ability versus the ancestral strain, suggesting an important role for diversification in the adaptation of B. thuringiensis to the biofilm lifestyle. Further genetic characterization of FS variant revealed the disruption of a guanylyltransferase gene by an insertion sequence (IS) element, which could be similarly observed in the genome of a natural isolate. The evolved FS and the deletion mutant in the guanylyltransferase gene (Bt407ΔrfbM) displayed similarly altered aggregation and hydrophobicity compared to the ancestor strain, suggesting that the adaptation process highly depends on the physical adhesive forces.}, } @article {pmid35417559, year = {2022}, author = {Kambayashi, C and Kakehashi, R and Sato, Y and Mizuno, H and Tanabe, H and Rakotoarison, A and Künzel, S and Furuno, N and Ohshima, K and Kumazawa, Y and Nagy, ZT and Mori, A and Allison, A and Donnellan, SC and Ota, H and Hoso, M and Yanagida, T and Sato, H and Vences, M and Kurabayashi, A}, title = {Geography-Dependent Horizontal Gene Transfer from Vertebrate Predators to Their Prey.}, journal = {Molecular biology and evolution}, volume = {39}, number = {4}, pages = {}, pmid = {35417559}, issn = {1537-1719}, mesh = {Animals ; Cattle ; *Gene Transfer, Horizontal ; Geography ; *Parasites/genetics ; Phylogeny ; Predatory Behavior ; Retroelements ; Vertebrates/genetics ; }, abstract = {Horizontal transfer (HT) of genes between multicellular animals, once thought to be extremely rare, is being more commonly detected, but its global geographic trend and transfer mechanism have not been investigated. We discovered a unique HT pattern of Bovine-B (BovB) LINE retrotransposons in vertebrates, with a bizarre transfer direction from predators (snakes) to their prey (frogs). At least 54 instances of BovB HT were detected, which we estimate to have occurred across time between 85 and 1.3 Ma. Using comprehensive transcontinental sampling, our study demonstrates that BovB HT is highly prevalent in one geographical region, Madagascar, suggesting important regional differences in the occurrence of HTs. We discovered parasite vectors that may plausibly transmit BovB and found that the proportion of BovB-positive parasites is also high in Madagascar where BovB thus might be physically transported by parasites to diverse vertebrates, potentially including humans. Remarkably, in two frog lineages, BovB HT occurred after migration from a non-HT area (Africa) to the HT hotspot (Madagascar). These results provide a novel perspective on how the prevalence of parasites influences the occurrence of HT in a region, similar to pathogens and their vectors in some endemic diseases.}, } @article {pmid35409376, year = {2022}, author = {Kasperski, A}, title = {Life Entrapped in a Network of Atavistic Attractors: How to Find a Rescue.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409376}, issn = {1422-0067}, mesh = {Cell Physiological Phenomena ; Cell Transformation, Neoplastic/metabolism ; *Energy Metabolism ; Humans ; Mitochondria/metabolism ; *Neoplasms/metabolism ; }, abstract = {In view of unified cell bioenergetics, cell bioenergetic problems related to cell overenergization can cause excessive disturbances in current cell fate and, as a result, lead to a change of cell-fate. At the onset of the problem, cell overenergization of multicellular organisms (especially overenergization of mitochondria) is solved inter alia by activation and then stimulation of the reversible Crabtree effect by cells. Unfortunately, this apparently good solution can also lead to a much bigger problem when, despite the activation of the Crabtree effect, cell overenergization persists for a long time. In such a case, cancer transformation, along with the Warburg effect, may occur to further reduce or stop the charging of mitochondria by high-energy molecules. Understanding the phenomena of cancer transformation and cancer development has become a real challenge for humanity. To date, many models have been developed to understand cancer-related mechanisms. Nowadays, combining all these models into one coherent universal model of cancer transformation and development can be considered a new challenge. In this light, the aim of this article is to present such a potentially universal model supported by a proposed new model of cellular functionality evolution. The methods of fighting cancer resulting from unified cell bioenergetics and the two presented models are also considered.}, } @article {pmid35406795, year = {2022}, author = {Zschüntzsch, J and Meyer, S and Shahriyari, M and Kummer, K and Schmidt, M and Kummer, S and Tiburcy, M}, title = {The Evolution of Complex Muscle Cell In Vitro Models to Study Pathomechanisms and Drug Development of Neuromuscular Disease.}, journal = {Cells}, volume = {11}, number = {7}, pages = {}, pmid = {35406795}, issn = {2073-4409}, mesh = {Coculture Techniques ; Drug Development ; Humans ; Muscle Cells ; *Neuromuscular Diseases/drug therapy ; *Organoids ; }, abstract = {Many neuromuscular disease entities possess a significant disease burden and therapeutic options remain limited. Innovative human preclinical models may help to uncover relevant disease mechanisms and enhance the translation of therapeutic findings to strengthen neuromuscular disease precision medicine. By concentrating on idiopathic inflammatory muscle disorders, we summarize the recent evolution of the novel in vitro models to study disease mechanisms and therapeutic strategies. A particular focus is laid on the integration and simulation of multicellular interactions of muscle tissue in disease phenotypes in vitro. Finally, the requirements of a neuromuscular disease drug development workflow are discussed with a particular emphasis on cell sources, co-culture systems (including organoids), functionality, and throughput.}, } @article {pmid35396623, year = {2023}, author = {Koide, RT}, title = {On Holobionts, Holospecies, and Holoniches: the Role of Microbial Symbioses in Ecology and Evolution.}, journal = {Microbial ecology}, volume = {85}, number = {4}, pages = {1143-1149}, pmid = {35396623}, issn = {1432-184X}, mesh = {Phylogeny ; *Symbiosis ; *Adaptation, Physiological ; Eukaryota ; Biological Evolution ; }, abstract = {My goal in writing this is to increase awareness of the roles played by microbial symbionts in eukaryote ecology and evolution. Most eukaryotes host one or more species of symbiotic microorganisms, including prokaryotes and fungi. Many of these have profound impacts on the biology of their hosts. For example, microbial symbionts may expand the niches of their hosts, cause rapid adaptation of the host to the environment and re-adaptation to novel conditions via symbiont swapping, facilitate speciation, and fundamentally alter our concept of the species. In some cases, microbial symbionts and multicellular eukaryote hosts have a mutual dependency, which has obvious conservation implications. Hopefully, this contribution will stimulate a reevaluation of important ecological and evolutionary concepts including niche, adaptation, the species, speciation, and conservation of multicellular eukaryotes.}, } @article {pmid35395246, year = {2022}, author = {Yang, Y and Jiang, H}, title = {Intercellular water exchanges trigger soliton-like waves in multicellular systems.}, journal = {Biophysical journal}, volume = {121}, number = {9}, pages = {1610-1618}, pmid = {35395246}, issn = {1542-0086}, mesh = {*Water ; }, abstract = {Oscillations and waves are ubiquitous in living cellular systems. Generations of these spatiotemporal patterns are generally attributed to some mechanochemical feedbacks. Here, we treat cells as open systems, i.e., water and ions can pass through the cell membrane passively or actively, and reveal a new origin of wave generation. We show that osmotic shocks above a shock threshold will trigger self-sustained cell oscillations and result in long-range waves propagating without decrement, a phenomenon that is analogous to the excitable medium. The traveling wave propagates along the intercellular osmotic pressure gradient, and its wave speed scales with the magnitude of intercellular water flows. Furthermore, we also find that the traveling wave exhibits several hallmarks of solitary waves. Together, our findings predict a new mechanism of wave generation in living multicellular systems. The ubiquity of intercellular water exchanges implies that this mechanism may be relevant to a broad class of systems.}, } @article {pmid35394842, year = {2022}, author = {Dupin, A and Aufinger, L and Styazhkin, I and Rothfischer, F and Kaufmann, BK and Schwarz, S and Galensowske, N and Clausen-Schaumann, H and Simmel, FC}, title = {Synthetic cell-based materials extract positional information from morphogen gradients.}, journal = {Science advances}, volume = {8}, number = {14}, pages = {eabl9228}, pmid = {35394842}, issn = {2375-2548}, abstract = {Biomaterials composed of synthetic cells have the potential to adapt and differentiate guided by physicochemical environmental cues. Inspired by biological systems in development, which extract positional information (PI) from morphogen gradients in the presence of uncertainties, we here investigate how well synthetic cells can determine their position within a multicellular structure. To calculate PI, we created and analyzed a large number of synthetic cellular assemblies composed of emulsion droplets connected via lipid bilayer membranes. These droplets contained cell-free feedback gene circuits that responded to gradients of a genetic inducer acting as a morphogen. PI is found to be limited by gene expression noise and affected by the temporal evolution of the morphogen gradient and the cell-free expression system itself. The generation of PI can be rationalized by computational modeling of the system. We scale our approach using three-dimensional printing and demonstrate morphogen-based differentiation in larger tissue-like assemblies.}, } @article {pmid35391738, year = {2022}, author = {Nagy, K and Dukic, B and Hodula, O and Ábrahám, Á and Csákvári, E and Dér, L and Wetherington, MT and Noorlag, J and Keymer, JE and Galajda, P}, title = {Emergence of Resistant Escherichia coli Mutants in Microfluidic On-Chip Antibiotic Gradients.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {820738}, pmid = {35391738}, issn = {1664-302X}, abstract = {Spatiotemporal structures and heterogeneities are common in natural habitats, yet their role in the evolution of antibiotic resistance is still to be uncovered. We applied a microfluidic gradient generator device to study the emergence of resistant bacteria in spatial ciprofloxacin gradients. We observed biofilm formation in regions with sub-inhibitory concentrations of antibiotics, which quickly expanded into the high antibiotic regions. In the absence of an explicit structure of the habitat, this multicellular formation led to a spatial structure of the population with local competition and limited migration. Therefore, such structures can function as amplifiers of selection and aid the spread of beneficial mutations. We found that the physical environment itself induces stress-related mutations that later prove beneficial when cells are exposed to antibiotics. This shift in function suggests that exaptation occurs in such experimental scenarios. The above two processes pave the way for the subsequent emergence of highly resistant specific mutations.}, } @article {pmid35386829, year = {2022}, author = {van der Zee, MJ and Whiting, JR and Paris, JR and Bassar, RD and Travis, J and Weigel, D and Reznick, DN and Fraser, BA}, title = {Rapid genomic convergent evolution in experimental populations of Trinidadian guppies (Poecilia reticulata).}, journal = {Evolution letters}, volume = {6}, number = {2}, pages = {149-161}, pmid = {35386829}, issn = {2056-3744}, abstract = {Although rapid phenotypic evolution has been documented often, the genomic basis of rapid adaptation to natural environments is largely unknown in multicellular organisms. Population genomic studies of experimental populations of Trinidadian guppies (Poecilia reticulata) provide a unique opportunity to study this phenomenon. Guppy populations that were transplanted from high-predation (HP) to low-predation (LP) environments have been shown to evolve toward the phenotypes of naturally colonized LP populations in as few as eight generations. These changes persist in common garden experiments, indicating that they have a genetic basis. Here, we report results of whole genome variation in four experimental populations colonizing LP sites along with the corresponding HP source population. We examined genome-wide patterns of genetic variation to estimate past demography and used a combination of genome scans, forward simulations, and a novel analysis of allele frequency change vectors to uncover the signature of selection. We detected clear signals of population growth and bottlenecks at the genome-wide level that matched the known history of population numbers. We found a region on chromosome 15 under strong selection in three of the four populations and with our multivariate approach revealing subtle parallel changes in allele frequency in all four populations across this region. Investigating patterns of genome-wide selection in this uniquely replicated experiment offers remarkable insight into the mechanisms underlying rapid adaptation, providing a basis for comparison with other species and populations experiencing rapidly changing environments.}, } @article {pmid35369456, year = {2022}, author = {Chen, K and Gao, Y and Li, L and Zhang, W and Li, J and Zhou, Z and He, H and Chen, Z and Liao, M and Zhang, J}, title = {Increased Drug Resistance and Biofilm Formation Ability in ST34-Type Salmonella Typhimurium Exhibiting Multicellular Behavior in China.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {876500}, pmid = {35369456}, issn = {1664-302X}, abstract = {Salmonella Typhimurium is an important food-borne pathogen. In this paper, multicellular behavior and associated characteristics of S. Typhimurium isolated from human and animal source food were studied. All the S. Typhimurium strains exhibiting multicellular behavior (100%) belonged to the ST34 type. In addition, most of the ST34-type multicellular behavior S. Typhimurium strains had a human origin (69.11%) and 98% of the ST34-type multicellular behavior strains exhibited strong biofilm formation capacity, which was much higher than that of non-multicellular behavior strains (7%, P < 0.01). Antibiotic resistance in ST34-type multicellular behavior strains was significantly higher than in strains with non-multicellular behavior for most conventional drugs (P < 0.05); notably, Polymyxin B (8%) and Imipenem (1%) resistances were also observed in the ST34-type strains. Furthermore, all the ST34-type multicellular behavior strains (100%) exhibited Multiple Drug Resistance (resistance to ≥3antibiotics), which was much higher than that of the non-multicellular behavior strains (P < 0.05). Consistent with the drug-resistant phenotype, the carrying rates of most drug-resistant genes in ST34-type multicellular behavior strains were higher than that those in non-multicellular behavior strains (P < 0.05). Therefore, this study revealed the emergence of a prevalent ST34-type multicellular behavior S. Typhimurium strains with increased biofilm formation ability and drug resistance rate, which poses a threat to public health safety, and highlights the need for comprehensive monitoring of the strains.}, } @article {pmid35359304, year = {2022}, author = {Ramon-Mateu, J and Edgar, A and Mitchell, D and Martindale, MQ}, title = {Studying Ctenophora WBR Using Mnemiopsis leidyi.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2450}, number = {}, pages = {95-119}, pmid = {35359304}, issn = {1940-6029}, mesh = {Animals ; Cell Lineage ; *Ctenophora/genetics ; Genome ; Phylogeny ; }, abstract = {Ctenophores, also known as comb jellies, are a clade of fragile holopelagic, carnivorous marine invertebrates, that represent one of the most ancient extant groups of multicellular animals. Ctenophores show a remarkable ability to regenerate in the adult form, being capable of replacing all body parts (i.e., whole-body regeneration) after loss/amputation. With many favorable experimental features (optical clarity, stereotyped cell lineage, multiple cell types), a full genome sequence available and their early branching phylogenetic position, ctenophores are well placed to provide information about the evolution of regenerative ability throughout the Metazoa. Here, we provide a collection of detailed protocols for use of the lobate ctenophore Mnemiopsis leidyi to study whole-body regeneration, including specimen collection, husbandry, surgical manipulation, and imaging techniques.}, } @article {pmid35358607, year = {2022}, author = {Shapiro, JA}, title = {What we have learned about evolutionary genome change in the past 7 decades.}, journal = {Bio Systems}, volume = {215-216}, number = {}, pages = {104669}, doi = {10.1016/j.biosystems.2022.104669}, pmid = {35358607}, issn = {1872-8324}, mesh = {Animals ; *Biological Evolution ; *DNA Transposable Elements/genetics ; Eukaryota/genetics ; Evolution, Molecular ; Genomics ; Hybridization, Genetic ; }, abstract = {Cytogenetics and genomics have completely transformed our understanding of evolutionary genome change since the early 1950s. The point of this paper is to outline some of the empirical findings responsible for that transformation. The discovery of transposable elements (TEs) in maize by McClintock, and their subsequent rediscovery in all forms of life, tell us that organisms have the inherent capacity to evolve dispersed genomic networks encoding complex cellular and multicellular adaptations. Genomic analysis confirms the role of TEs in wiring novel networks at major evolutionary transitions. TEs and other forms of repetitive DNA are also important contributors to genome regions that serve as transcriptional templates for regulatory and other biologically functional noncoding ncRNAs. The many functions documented for ncRNAs shows the concept of abundant "selfish" or "junk" DNA in complex genomes is mistaken. Natural and artificial speciation by interspecific hybridization demonstrates that TEs and other biochemical systems of genome restructuring are subject to rapid activation and can generate changes throughout the genomes of the novel species that emerge. In addition to TEs and hybrid species, cancer cells have taught us important lessons about chromothripsis, chromoplexy and other forms of non-random multisite genome restructuring. In many of these restructured genomes, alternative end-joining processes display the capacities of eukaryotes to generate novel combinations of templated and untemplated DNA sequences at the sites of break repair. Sequence innovation by alternative end-joining is widespread among eukaryotes from single cells to advanced plants and animals. In sum, the cellular and genomic capacities of eukaryotic cells have proven to be capable of executing rapid macroevolutionary change under a variety of conditions.}, } @article {pmid35353805, year = {2022}, author = {Burnetti, A and Ratcliff, WC}, title = {Experimental evolution is not just for model organisms.}, journal = {PLoS biology}, volume = {20}, number = {3}, pages = {e3001587}, pmid = {35353805}, issn = {1545-7885}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; }, abstract = {In a new paper published in PLOS Biology, Dudin and colleagues evolve simple multicellularity in Sphaeroforma arctica, a unicellular relative of animals. This work establishes a new and open-ended avenue for examining the evolution of multicellularity in an important but understudied group of organisms.}, } @article {pmid35349792, year = {2022}, author = {Toret, C and Picco, A and Boiero-Sanders, M and Michelot, A and Kaksonen, M}, title = {The cellular slime mold Fonticula alba forms a dynamic, multicellular collective while feeding on bacteria.}, journal = {Current biology : CB}, volume = {32}, number = {9}, pages = {1961-1973.e4}, pmid = {35349792}, issn = {1879-0445}, mesh = {Animals ; Bacteria ; *Dictyosteliida ; Eukaryota ; Fungi ; Phylogeny ; }, abstract = {Multicellularity evolved in fungi and animals, or the opisthokonts, from their common amoeboflagellate ancestor but resulted in strikingly distinct cellular organizations. The origins of this multicellularity divergence are not known. The stark mechanistic differences that underlie the two groups and the lack of information about ancestral cellular organizations limits progress in this field. We discovered a new type of invasive multicellular behavior in Fonticula alba, a unique species in the opisthokont tree, which has a simple, bacteria-feeding sorocarpic amoeba lifestyle. This invasive multicellularity follows germination dependent on the bacterial culture state, after which amoebae coalesce to form dynamic collectives that invade virgin bacterial resources. This bacteria-dependent social behavior emerges from amoeba density and allows for rapid and directed invasion. The motile collectives have animal-like properties but also hyphal-like search and invasive behavior. These surprising findings enrich the diverse multicellularities present within the opisthokont lineage and offer a new perspective on fungal origins.}, } @article {pmid35349578, year = {2022}, author = {Dudin, O and Wielgoss, S and New, AM and Ruiz-Trillo, I}, title = {Regulation of sedimentation rate shapes the evolution of multicellularity in a close unicellular relative of animals.}, journal = {PLoS biology}, volume = {20}, number = {3}, pages = {e3001551}, pmid = {35349578}, issn = {1545-7885}, mesh = {Animals ; Cell Size ; *Cytokinesis ; Phenotype ; }, abstract = {Significant increases in sedimentation rate accompany the evolution of multicellularity. These increases should lead to rapid changes in ecological distribution, thereby affecting the costs and benefits of multicellularity and its likelihood to evolve. However, how genetic and cellular traits control this process, their likelihood of emergence over evolutionary timescales, and the variation in these traits as multicellularity evolves are still poorly understood. Here, using isolates of the ichthyosporean genus Sphaeroforma-close unicellular relatives of animals with brief transient multicellular life stages-we demonstrate that sedimentation rate is a highly variable and evolvable trait affected by at least 2 distinct physical mechanisms. First, we find extensive (>300×) variation in sedimentation rates for different Sphaeroforma species, mainly driven by size and density during the unicellular-to-multicellular life cycle transition. Second, using experimental evolution with sedimentation rate as a focal trait, we readily obtained, for the first time, fast settling and multicellular Sphaeroforma arctica isolates. Quantitative microscopy showed that increased sedimentation rates most often arose by incomplete cellular separation after cell division, leading to clonal "clumping" multicellular variants with increased size and density. Strikingly, density increases also arose by an acceleration of the nuclear doubling time relative to cell size. Similar size- and density-affecting phenotypes were observed in 4 additional species from the Sphaeroforma genus, suggesting that variation in these traits might be widespread in the marine habitat. By resequencing evolved isolates to high genomic coverage, we identified mutations in regulators of cytokinesis, plasma membrane remodeling, and chromatin condensation that may contribute to both clump formation and the increase in the nuclear number-to-volume ratio. Taken together, this study illustrates how extensive cellular control of density and size drive sedimentation rate variation, likely shaping the onset and further evolution of multicellularity.}, } @article {pmid35337467, year = {2022}, author = {Booth, DS and King, N}, title = {The history of Salpingoeca rosetta as a model for reconstructing animal origins.}, journal = {Current topics in developmental biology}, volume = {147}, number = {}, pages = {73-91}, doi = {10.1016/bs.ctdb.2022.01.001}, pmid = {35337467}, issn = {1557-8933}, mesh = {Animals ; *Choanoflagellata/genetics ; Developmental Biology ; }, abstract = {Choanoflagellates, the closest living relatives of animals, have the potential to reveal the genetic and cell biological foundations of complex multicellular development in animals. Here we describe the history of research on the choanoflagellate Salpingoeca rosetta. From its original isolation in 2000 to the establishment of CRISPR-mediated genome editing in 2020, S. rosetta provides an instructive case study in the establishment of a new model organism.}, } @article {pmid35320517, year = {2022}, author = {Verkerke, H and Dias-Baruffi, M and Cummings, RD and Arthur, CM and Stowell, SR}, title = {Galectins: An Ancient Family of Carbohydrate Binding Proteins with Modern Functions.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2442}, number = {}, pages = {1-40}, pmid = {35320517}, issn = {1940-6029}, mesh = {Cell Cycle ; *Galectins/metabolism ; Glycosylation ; *Immune System/metabolism ; Signal Transduction ; }, abstract = {Galectins are a large family of carbohydrate binding proteins with members in nearly every lineage of multicellular life. Through tandem and en-mass genome duplications, over 15 known vertebrate galectins likely evolved from a single common ancestor extant in pre-chordate lineages. While galectins have divergently evolved numerous functions, some of which do not involve carbohydrate recognition, the vast majority of the galectins have retained the conserved ability to bind variably modified polylactosamine (polyLacNAc) residues on glycans that modify proteins and lipids on the surface of host cells and pathogens. In addition to their direct role in microbial killing, many proposed galectin functions in the immune system and cancer involve crosslinking glycosylated receptors and modifying signaling pathways or sensitivity to antigen from the outside in. However, a large body of work has uncovered intracellular galectin functions mediated by carbohydrate- and non-carbohydrate-dependent interactions. In the cytoplasm, galectins can tune intracellular kinase and G-protein-coupled signaling cascades important for nutrient sensing, cell cycle progression, and transformation. Particularly, but interconnected pathways, cytoplasmic galectins serve the innate immune system as sensors of endolysosomal damage, recruiting and assembling the components of autophagosomes during intracellular infection through carbohydrate-dependent and -independent activities. In the nucleus, galectins participate in pre-mRNA splicing perhaps through interactions with non-coding RNAs required for assembly of spliceosomes. Together, studies of galectin function paint a picture of a functionally dynamic protein family recruited during eons of evolution to regulate numerous essential cellular processes in the context of multicellular life.}, } @article {pmid35318703, year = {2022}, author = {Hammond, M and Dorrell, RG and Speijer, D and Lukeš, J}, title = {Eukaryotic cellular intricacies shape mitochondrial proteomic complexity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {44}, number = {5}, pages = {e2100258}, doi = {10.1002/bies.202100258}, pmid = {35318703}, issn = {1521-1878}, mesh = {Biological Evolution ; Eukaryota/physiology ; *Eukaryotic Cells/metabolism ; Mitochondria/metabolism ; Organelles/metabolism ; Phylogeny ; *Proteomics ; }, abstract = {Mitochondria have been fundamental to the eco-physiological success of eukaryotes since the last eukaryotic common ancestor (LECA). They contribute essential functions to eukaryotic cells, above and beyond classical respiration. Mitochondria interact with, and complement, metabolic pathways occurring in other organelles, notably diversifying the chloroplast metabolism of photosynthetic organisms. Here, we integrate existing literature to investigate how mitochondrial metabolism varies across the landscape of eukaryotic evolution. We illustrate the mitochondrial remodelling and proteomic changes undergone in conjunction with major evolutionary transitions. We explore how the mitochondrial complexity of the LECA has been remodelled in specific groups to support subsequent evolutionary transitions, such as the acquisition of chloroplasts in photosynthetic species and the emergence of multicellularity. We highlight the versatile and crucial roles played by mitochondria during eukaryotic evolution, extending from its huge contribution to the development of the LECA itself to the dynamic evolution of individual eukaryote groups, reflecting both their current ecologies and evolutionary histories.}, } @article {pmid35317961, year = {2023}, author = {Bogaert, KA and Zakka, EE and Coelho, SM and De Clerck, O}, title = {Polarization of brown algal zygotes.}, journal = {Seminars in cell & developmental biology}, volume = {134}, number = {}, pages = {90-102}, doi = {10.1016/j.semcdb.2022.03.008}, pmid = {35317961}, issn = {1096-3634}, mesh = {Animals ; Zygote ; *Arabidopsis ; *Phaeophyta/genetics/metabolism ; Cell Polarity ; Cell Division ; Plants ; }, abstract = {Brown algae are a group of multicellular, heterokont algae that have convergently evolved developmental complexity that rivals that of embryophytes, animals or fungi. Early in development, brown algal zygotes establish a basal and an apical pole, which will become respectively the basal system (holdfast) and the apical system (thallus) of the adult alga. Brown algae are interesting models for understanding the establishment of cell polarity in a broad evolutionary context, because they exhibit a large diversity of life cycles, reproductive strategies and, importantly, their zygotes are produced in large quantities free of parental tissue, with symmetry breaking and asymmetric division taking place in a highly synchronous manner. This review describes the current knowledge about the establishment of the apical-basal axis in the model brown seaweeds Ectocarpus, Dictyota, Fucus and Saccharina, highlighting the advantages and specific interests of each system. Ectocarpus is a genetic model system that allows access to the molecular basis of early development and life-cycle control over apical-basal polarity. The oogamous brown alga Fucus, together with emerging comparative models Dictyota and Saccharina, emphasize the diversity of strategies of symmetry breaking in determining a cell polarity vector in brown algae. A comparison with symmetry-breaking mechanisms in land plants, animals and fungi, reveals that the one-step zygote polarisation of Fucus compares well to Saccharomyces budding and Arabidopsis stomata development, while the two-phased symmetry breaking in the Dictyota zygote compares to Schizosaccharomyces fission, the Caenorhabditis anterior-posterior zygote polarisation and Arabidopsis prolate pollen polarisation. The apical-basal patterning in Saccharina zygotes on the other hand, may be seen as analogous to that of land plants. Overall, brown algae have the potential to bring exciting new information on how a single cell gives rise to an entire complex body plan.}, } @article {pmid35311270, year = {2022}, author = {Chen, C and Wang, P and Chen, H and Wang, X and Halgamuge, MN and Chen, C and Song, T}, title = {Smart Magnetotactic Bacteria Enable the Inhibition of Neuroblastoma under an Alternating Magnetic Field.}, journal = {ACS applied materials & interfaces}, volume = {14}, number = {12}, pages = {14049-14058}, doi = {10.1021/acsami.1c24154}, pmid = {35311270}, issn = {1944-8252}, mesh = {Animals ; *Hyperthermia, Induced ; Magnetic Fields ; *Magnetosomes/metabolism ; Mice ; Mice, Nude ; *Neuroblastoma/metabolism/therapy ; }, abstract = {Magnetotactic bacteria are ubiquitous microorganisms in nature that synthesize intracellular magnetic nanoparticles called magnetosomes in a gene-controlled way and arrange them in chains. From in vitro to in vivo, we demonstrate that the intact body of Magnetospirillum magneticum AMB-1 has potential as a natural magnetic hyperthermia material for cancer therapy. Compared to chains of magnetosomes and individual magnetosomes, the entire AMB-1 cell exhibits superior heating capability under an alternating magnetic field. When incubating with tumor cells, the intact AMB-1 cells disperse better than the other two types of magnetosomes, decreasing cellular viability under the control of an alternating magnetic field. Furthermore, in vivo experiments in nude mice with neuroblastoma found that intact AMB-1 cells had the best antitumor activity with magnetic hyperthermia therapy compared to other treatment groups. These findings suggest that the intact body of magnetotactic bacteria has enormous promise as a natural material for tumor magnetic hyperthermia. In biomedical applications, intact and living magnetotactic bacteria play an increasingly essential function as a targeting robot due to their magnetotaxis.}, } @article {pmid35295942, year = {2022}, author = {Jiménez-Marín, B and Olson, BJSC}, title = {The Curious Case of Multicellularity in the Volvocine Algae.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {787665}, pmid = {35295942}, issn = {1664-8021}, abstract = {The evolution of multicellularity is a major evolutionary transition that underlies the radiation of many species in all domains of life, especially in eukaryotes. The volvocine green algae are an unconventional model system that holds great promise in the field given its genetic tractability, late transition to multicellularity, and phenotypic diversity. Multiple efforts at linking multicellularity-related developmental landmarks to key molecular changes, especially at the genome level, have provided key insights into the molecular innovations or lack thereof that underlie multicellularity. Twelve developmental changes have been proposed to explain the evolution of complex differentiated multicellularity in the volvocine algae. Co-option of key genes, such as cell cycle and developmental regulators has been observed, but with few exceptions, known co-option events do not seem to coincide with most developmental features observed in multicellular volvocines. The apparent lack of "master multicellularity genes" combined with no apparent correlation between gene gains for developmental processes suggest the possibility that many multicellular traits might be the product gene-regulatory and functional innovations; in other words, multicellularity can arise from shared genomic repertoires that undergo regulatory and functional overhauls.}, } @article {pmid35294281, year = {2022}, author = {Pichugin, Y and Traulsen, A}, title = {The possible modes of microbial reproduction are fundamentally restricted by distribution of mass between parent and offspring.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {12}, pages = {e2122197119}, pmid = {35294281}, issn = {1091-6490}, mesh = {*Bacteria ; *Reproduction ; }, abstract = {Multiple modes of asexual reproduction are observed among microbial organisms in natural populations. These modes are not only subject to evolution, but may drive evolutionary competition directly through their impact on population growth rates. The most prominent transition between two such modes is the one from unicellularity to multicellularity. We present a model of the evolution of reproduction modes, where a parent organism fragments into smaller parts. While the size of an organism at fragmentation, the number of offspring, and their sizes may vary a lot, the combined mass of fragments is limited by the mass of the parent organism. We found that mass conservation can fundamentally limit the number of possible reproduction modes. This has important direct implications for microbial life: For unicellular species, the interplay between cell shape and kinetics of the cell growth implies that the largest and the smallest possible cells should be rod shaped rather than spherical. For primitive multicellular species, these considerations can explain why rosette cell colonies evolved a mechanistically complex binary split reproduction. Finally, we show that the loss of organism mass during sporulation can explain the macroscopic sizes of the formally unicellular microorganism Myxomycetes plasmodium. Our findings demonstrate that a number of seemingly unconnected phenomena observed in unrelated species may be different manifestations of the same underlying process.}, } @article {pmid35287173, year = {2022}, author = {Benureau, FCY and Tani, J}, title = {Morphological Development at the Evolutionary Timescale: Robotic Developmental Evolution.}, journal = {Artificial life}, volume = {28}, number = {1}, pages = {3-21}, doi = {10.1162/artl_a_00357}, pmid = {35287173}, issn = {1530-9185}, mesh = {Algorithms ; Gait ; Learning ; Phylogeny ; *Robotics/methods ; }, abstract = {Evolution and development operate at different timescales; generations for the one, a lifetime for the other. These two processes, the basis of much of life on earth, interact in many non-trivial ways, but their temporal hierarchy-evolution overarching development-is observed for most multicellular life forms. When designing robots, however, this tenet lifts: It becomes-however natural-a design choice. We propose to inverse this temporal hierarchy and design a developmental process happening at the phylogenetic timescale. Over a classic evolutionary search aimed at finding good gaits for tentacle 2D robots, we add a developmental process over the robots' morphologies. Within a generation, the morphology of the robots does not change. But from one generation to the next, the morphology develops. Much like we become bigger, stronger, and heavier as we age, our robots are bigger, stronger, and heavier with each passing generation. Our robots start with baby morphologies, and a few thousand generations later, end-up with adult ones. We show that this produces better and qualitatively different gaits than an evolutionary search with only adult robots, and that it prevents premature convergence by fostering exploration. In addition, we validate our method on voxel lattice 3D robots from the literature and compare it to a recent evolutionary developmental approach. Our method is conceptually simple, and it can be effective on small or large populations of robots, and intrinsic to the robot and its morphology, not the task or environment. Furthermore, by recasting the evolutionary search as a learning process, these results can be viewed in the context of developmental learning robotics.}, } @article {pmid35251134, year = {2022}, author = {Palazzo, AF and Kejiou, NS}, title = {Non-Darwinian Molecular Biology.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {831068}, pmid = {35251134}, issn = {1664-8021}, abstract = {With the discovery of the double helical structure of DNA, a shift occurred in how biologists investigated questions surrounding cellular processes, such as protein synthesis. Instead of viewing biological activity through the lens of chemical reactions, this new field used biological information to gain a new profound view of how biological systems work. Molecular biologists asked new types of questions that would have been inconceivable to the older generation of researchers, such as how cellular machineries convert inherited biological information into functional molecules like proteins. This new focus on biological information also gave molecular biologists a way to link their findings to concepts developed by genetics and the modern synthesis. However, by the late 1960s this all changed. Elevated rates of mutation, unsustainable genetic loads, and high levels of variation in populations, challenged Darwinian evolution, a central tenant of the modern synthesis, where adaptation was the main driver of evolutionary change. Building on these findings, Motoo Kimura advanced the neutral theory of molecular evolution, which advocates that selection in multicellular eukaryotes is weak and that most genomic changes are neutral and due to random drift. This was further elaborated by Jack King and Thomas Jukes, in their paper "Non-Darwinian Evolution", where they pointed out that the observed changes seen in proteins and the types of polymorphisms observed in populations only become understandable when we take into account biochemistry and Kimura's new theory. Fifty years later, most molecular biologists remain unaware of these fundamental advances. Their adaptionist viewpoint fails to explain data collected from new powerful technologies which can detect exceedingly rare biochemical events. For example, high throughput sequencing routinely detects RNA transcripts being produced from almost the entire genome yet are present less than one copy per thousand cells and appear to lack any function. Molecular biologists must now reincorporate ideas from classical biochemistry and absorb modern concepts from molecular evolution, to craft a new lens through which they can evaluate the functionality of transcriptional units, and make sense of our messy, intricate, and complicated genome.}, } @article {pmid35247708, year = {2022}, author = {Tong, K and Bozdag, GO and Ratcliff, WC}, title = {Selective drivers of simple multicellularity.}, journal = {Current opinion in microbiology}, volume = {67}, number = {}, pages = {102141}, doi = {10.1016/j.mib.2022.102141}, pmid = {35247708}, issn = {1879-0364}, mesh = {*Biological Evolution ; }, abstract = {In order to understand the evolution of multicellularity, we must understand how and why selection favors the first steps in this process: the evolution of simple multicellular groups. Multicellularity has evolved many times in independent lineages with fundamentally different ecologies, yet no work has yet systematically examined these diverse selective drivers. Here we review recent developments in systematics, comparative biology, paleontology, synthetic biology, theory, and experimental evolution, highlighting ten selective drivers of simple multicellularity. Our survey highlights the many ecological opportunities available for simple multicellularity, and stresses the need for additional work examining how these first steps impact the subsequent evolution of complex multicellularity.}, } @article {pmid35246710, year = {2022}, author = {Frenkel-Pinter, M and Petrov, AS and Matange, K and Travisano, M and Glass, JB and Williams, LD}, title = {Adaptation and Exaptation: From Small Molecules to Feathers.}, journal = {Journal of molecular evolution}, volume = {90}, number = {2}, pages = {166-175}, pmid = {35246710}, issn = {1432-1432}, support = {80NSSC18K1139/ImNASA/Intramural NASA/United States ; }, mesh = {Acclimatization ; *Adaptation, Physiological/genetics ; Animals ; Biological Evolution ; *Feathers ; }, abstract = {Evolution works by adaptation and exaptation. At an organismal level, exaptation and adaptation are seen in the formation of organelles and the advent of multicellularity. At the sub-organismal level, molecular systems such as proteins and RNAs readily undergo adaptation and exaptation. Here we suggest that the concepts of adaptation and exaptation are universal, synergistic, and recursive and apply to small molecules such as metabolites, cofactors, and the building blocks of extant polymers. For example, adenosine has been extensively adapted and exapted throughout biological evolution. Chemical variants of adenosine that are products of adaptation include 2' deoxyadenosine in DNA and a wide array of modified forms in mRNAs, tRNAs, rRNAs, and viral RNAs. Adenosine and its variants have been extensively exapted for various functions, including informational polymers (RNA, DNA), energy storage (ATP), metabolism (e.g., coenzyme A), and signaling (cyclic AMP). According to Gould, Vrba, and Darwin, exaptation imposes a general constraint on interpretation of history and origins; because of exaptation, extant function should not be used to explain evolutionary history. While this notion is accepted in evolutionary biology, it can also guide the study of the chemical origins of life. We propose that (i) evolutionary theory is broadly applicable from the dawn of life to the present time from molecules to organisms, (ii) exaptation and adaptation were important and simultaneous processes, and (iii) robust origin of life models can be constructed without conflating extant utility with historical basis of origins.}, } @article {pmid35246304, year = {2022}, author = {Li, XG and Jiao, ZX and Zhang, HH and Xu, J and Zhang, WJ and Qi, XQ and Wu, LF}, title = {Complete genome sequence of Crassaminicella sp. 143-21,isolated from a deep-sea hydrothermal vent.}, journal = {Marine genomics}, volume = {62}, number = {}, pages = {100899}, doi = {10.1016/j.margen.2021.100899}, pmid = {35246304}, issn = {1876-7478}, mesh = {Base Composition ; Clostridiaceae/genetics ; Genome, Bacterial ; *Hydrothermal Vents/microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/microbiology ; Sequence Analysis, DNA ; }, abstract = {Crassaminicella sp. 143-21, a putative new species isolated from deep-sea hydrothermal vent chimney on the Central Indian Ridge (CIR), is an anaerobic, thermophilic and rod-shaped bacterium belonging to the family Clostridiaceae. In this study, we present the complete genome sequence of strain 143-21, comprising 2,756,133 bp with a G + C content of 31.1%. In total, 2427 protein coding genes, 121 tRNA genes and 33 rRNA genes were obtained. Genomic analysis of strain 143-21 revealed that numerous genes related to organic matter transport and catabolism, including peptide transport, amino acid transport, saccharide transport, ethanolamine transport and corresponding metabolic pathways. Further, the genome contains a large proportion of genes involved in translation, ribosomal structure, and signal transduction. These genes might facilitate microbial survival in deep-sea hydrothermal vent environment. The genome of strain 143-21 will be helpful for further understanding its adaptive strategies in the deep-sea hydrothermal vent environment.}, } @article {pmid35235070, year = {2022}, author = {Kwantes, M and Wichard, T}, title = {The APAF1_C/WD40 repeat domain-encoding gene from the sea lettuce Ulva mutabilis sheds light on the evolution of NB-ARC domain-containing proteins in green plants.}, journal = {Planta}, volume = {255}, number = {4}, pages = {76}, pmid = {35235070}, issn = {1432-2048}, support = {SFB 1127/2 ChemBioSys//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Ecosystem ; Phylogeny ; Plant Proteins/metabolism ; Proteins/genetics ; *Ulva/genetics ; WD40 Repeats ; }, abstract = {We advance Ulva's genetic tractability and highlight its value as a model organism by characterizing its APAF1_C/WD40 domain-encoding gene, which belongs to a family that bears homology to R genes. The multicellular chlorophyte alga Ulva mutabilis (Ulvophyceae, Ulvales) is native to coastal ecosystems worldwide and attracts both high socio-economic and scientific interest. To further understand the genetic mechanisms that guide its biology, we present a protocol, based on adapter ligation-mediated PCR, for retrieving flanking sequences in U. mutabilis vector-insertion mutants. In the created insertional library, we identified a null mutant with an insertion in an apoptotic protease activating factor 1 helical domain (APAF1_C)/WD40 repeat domain-encoding gene. Protein domain architecture analysis combined with phylogenetic analysis revealed that this gene is a member of a subfamily that arose early in the evolution of green plants (Viridiplantae) through the acquisition of a gene that also encoded N-terminal nucleotide-binding adaptor shared by APAF-1, certain R-gene products and CED-4 (NB-ARC) and winged helix-like (WH-like) DNA-binding domains. Although phenotypic analysis revealed no mutant phenotype, gene expression levels in control plants correlated to the presence of bacterial symbionts, which U. mutabilis requires for proper morphogenesis. In addition, our analysis led to the discovery of a putative Ulva nucleotide-binding site and leucine-rich repeat (NBS-LRR) Resistance protein (R-protein), and we discuss how the emergence of these R proteins in green plants may be linked to the evolution of the APAF1_C/WD40 protein subfamily.}, } @article {pmid35232276, year = {2022}, author = {Gao, Y and Pichugin, Y and Gokhale, CS and Traulsen, A}, title = {Evolution of reproductive strategies in incipient multicellularity.}, journal = {Journal of the Royal Society, Interface}, volume = {19}, number = {188}, pages = {20210716}, pmid = {35232276}, issn = {1742-5662}, mesh = {*Biological Evolution ; Cell Communication ; *Reproduction ; }, abstract = {Multicellular organisms potentially show a large degree of diversity in reproductive strategies, producing offspring with varying sizes and compositions compared to their unicellular ancestors. In reality, only a few of these reproductive strategies are prevalent. To understand why this could be the case, we develop a stage-structured population model to probe the evolutionary growth advantages of reproductive strategies in incipient multicellular organisms. The performance of reproductive strategies is evaluated by the growth rates of the corresponding populations. We identify the optimal reproductive strategy, leading to the largest growth rate for a population. Considering the effects of organism size and cellular interaction, we found that distinct reproductive strategies could perform uniquely or equally well under different conditions. If a single reproductive strategy is optimal, it is binary splitting, dividing into two parts. Our results show that organism size and cellular interaction can play crucial roles in shaping reproductive strategies in nascent multicellularity. Our model sheds light on understanding the mechanism driving the evolution of reproductive strategies in incipient multicellularity. Beyond multicellularity, our results imply that a crucial factor in the evolution of unicellular species' reproductive strategies is organism size.}, } @article {pmid35218347, year = {2022}, author = {Spang, A and Mahendrarajah, TA and Offre, P and Stairs, CW}, title = {Evolving Perspective on the Origin and Diversification of Cellular Life and the Virosphere.}, journal = {Genome biology and evolution}, volume = {14}, number = {6}, pages = {}, pmid = {35218347}, issn = {1759-6653}, mesh = {*Archaea ; Biological Evolution ; Eukaryota ; Phylogeny ; *Viruses/genetics ; }, abstract = {The tree of life (TOL) is a powerful framework to depict the evolutionary history of cellular organisms through time, from our microbial origins to the diversification of multicellular eukaryotes that shape the visible biosphere today. During the past decades, our perception of the TOL has fundamentally changed, in part, due to profound methodological advances, which allowed a more objective approach to studying organismal and viral diversity and led to the discovery of major new branches in the TOL as well as viral lineages. Phylogenetic and comparative genomics analyses of these data have, among others, revolutionized our understanding of the deep roots and diversity of microbial life, the origin of the eukaryotic cell, eukaryotic diversity, as well as the origin, and diversification of viruses. In this review, we provide an overview of some of the recent discoveries on the evolutionary history of cellular organisms and their viruses and discuss a variety of complementary techniques that we consider crucial for making further progress in our understanding of the TOL and its interconnection with the virosphere.}, } @article {pmid35215297, year = {2022}, author = {Ashoorzadeh, A and Mowday, AM and Guise, CP and Silva, S and Bull, MR and Abbattista, MR and Copp, JN and Williams, EM and Ackerley, DF and Patterson, AV and Smaill, JB}, title = {Interrogation of the Structure-Activity Relationship of a Lipophilic Nitroaromatic Prodrug Series Designed for Cancer Gene Therapy Applications.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {15}, number = {2}, pages = {}, pmid = {35215297}, issn = {1424-8247}, support = {14/289//Health Research Council of New Zealand/ ; 17/255//Health Research Council of New Zealand/ ; }, abstract = {PR-104A is a dual hypoxia/nitroreductase gene therapy prodrug by virtue of its ability to undergo either one- or two-electron reduction to its cytotoxic species. It has been evaluated extensively in pre-clinical GDEPT studies, yet off-target human aldo-keto reductase AKR1C3-mediated activation has limited its use. Re-evaluation of this chemical scaffold has previously identified SN29176 as an improved hypoxia-activated prodrug analogue of PR-104A that is free from AKR1C3 activation. However, optimization of the bystander effect of SN29176 is required for use in a GDEPT setting to compensate for the non-uniform distribution of therapeutic gene transfer that is often observed with current gene therapy vectors. A lipophilic series of eight analogues were synthesized from commercially available 3,4-difluorobenzaldehyde. Calculated octanol-water partition coefficients (LogD7.4) spanned > 2 orders of magnitude. 2D anti-proliferative and 3D multicellular layer assays were performed using isogenic HCT116 cells expressing E. coli NfsA nitroreductase (NfsA_Ec) or AKR1C3 to determine enzyme activity and measure bystander effect. A variation in potency for NfsA_Ec was observed, while all prodrugs appeared AKR1C3-resistant by 2D assay. However, 3D assays indicated that increasing prodrug lipophilicity correlated with increased AKR1C3 activation and NfsA_Ec activity, suggesting that metabolite loss from the cell of origin into media during 2D monolayer assays could mask cytotoxicity. Three prodrugs were identified as bono fide AKR1C3-negative candidates whilst maintaining activity with NfsA_Ec. These were converted to their phosphate ester pre-prodrugs before being taken forward into in vivo therapeutic efficacy studies. Ultimately, 2-(5-(bis(2-bromoethyl)amino)-4-(ethylsulfonyl)-N-methyl-2-nitrobenzamido)ethyl dihydrogen phosphate possessed a significant 156% improvement in median survival in mixed NfsA_Ec/WT tumors compared to untreated controls (p = 0.005), whilst still maintaining hypoxia selectivity comparable to PR-104A.}, } @article {pmid35211015, year = {2022}, author = {Jackson-Patel, V and Liu, E and Bull, MR and Ashoorzadeh, A and Bogle, G and Wolfram, A and Hicks, KO and Smaill, JB and Patterson, AV}, title = {Tissue Pharmacokinetic Properties and Bystander Potential of Hypoxia-Activated Prodrug CP-506 by Agent-Based Modelling.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {803602}, pmid = {35211015}, issn = {1663-9812}, abstract = {Hypoxia-activated prodrugs are bioactivated in oxygen-deficient tumour regions and represent a novel strategy to exploit this pharmacological sanctuary for therapeutic gain. The approach relies on the selective metabolism of the prodrug under pathological hypoxia to generate active metabolites with the potential to diffuse throughout the tumour microenvironment and potentiate cell killing by means of a "bystander effect". In the present study, we investigate the pharmacological properties of the nitrogen mustard prodrug CP-506 in tumour tissues using in silico spatially-resolved pharmacokinetic/pharmacodynamic (SR-PK/PD) modelling. The approach employs a number of experimental model systems to define parameters for the cellular uptake, metabolism and diffusion of both the prodrug and its metabolites. The model predicts rapid uptake of CP-506 to high intracellular concentrations with its long plasma half-life driving tissue diffusion to a penetration depth of 190 µm, deep within hypoxic activating regions. While bioreductive metabolism is restricted to regions of severe pathological hypoxia (<1 µM O2), its active metabolites show substantial bystander potential with release from the cell of origin into the extracellular space. Model predictions of bystander efficiency were validated using spheroid co-cultures, where the clonogenic killing of metabolically defective "target" cells increased with the proportion of metabolically competent "activator" cells. Our simulations predict a striking bystander efficiency at tissue-like densities with the bis-chloro-mustard amine metabolite (CP-506M-Cl2) identified as a major diffusible metabolite. Overall, this study shows that CP-506 has favourable pharmacological properties in tumour tissue and supports its ongoing development for use in the treatment of patients with advanced solid malignancies.}, } @article {pmid35207574, year = {2022}, author = {Smith, D and Palacios-Pérez, M and Jheeta, S}, title = {The Enclosed Intestinal Microbiome: Semiochemical Signals from the Precambrian and Their Disruption by Heavy Metal Pollution.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35207574}, issn = {2075-1729}, abstract = {It is increasingly likely that many non-communicable diseases of humans and associated animals are due to the degradation of their intestinal microbiomes, a situation often referred to as dysbiosis. An analysis of the resultant diseases offers an opportunity to probe the function of these microbial partners of multicellular animals. In our view, it now seems likely that vertebrate animals and their microbiomes have coevolved throughout the Ediacaran-Cambrian transition and beyond, operating by semiochemical messaging between the multicellular host and its microbial community guest. A consideration of the overall role of the mutualistic intestinal microbiome as an enclosed bioreactor throws up a variety of challenging concepts. In particular: the significance of the microbiome with respect to the immune system suggests that microeukaryotes could act as microbial sentinel cells; the ubiquity of bacteriophage viruses implies the rapid turnover of microbial composition by a viral-shunt mechanism; and high microbial diversity is needed to ensure that horizontal gene transfer allows valuable genetic functions to be expressed. We have previously postulated that microbes of sufficient diversity must be transferred from mother to infant by seemingly accidental contamination during the process of natural birth. We termed this maternal microbial inheritance and suggested that it operates alongside parental genetic inheritance to modify gene expression. In this way, the adjustment of the neonate immune system by the microbiome may represent one of the ways in which the genome of a vertebrate animal interacts with its microbial environment. The absence of such critical functions in the neonate may help to explain the observation of persistent immune-system problems in affected adults. Equally, granted that the survival of the guest microbiome depends on the viability of its host, one function of microbiome-generated semiochemicals could be to facilitate the movement of food through the digestive tract, effectively partitioning nutrition between host and guest. In the event of famine, downregulation of microbial growth and therefore of semiochemical production would allow all available food to be consumed by the host. Although it is often thought that non-communicable diseases, such as type 2 diabetes, are caused by consumption of food containing insufficient dietary fibre, our hypothesis suggests that poor-quality food is not the prime cause but that the tendency for disease follows the degradation of the intestinal microbiome, when fat build-up occurs because the relevant semiochemicals can no longer be produced. It is the purpose of this paper to highlight the possibility that the origins of the microbiome lie in the Precambrian and that the disconnection of body and microbiome gives rise to non-communicable disease through the loss of semiochemical signalling. We further surmise that this disconnect has been largely brought about by heavy metal poisoning, potentially illuminating a facet of the exposome, the sum total of environmental insults that influence the expression of the genetic inheritance of an animal.}, } @article {pmid35205423, year = {2022}, author = {Alfieri, JM and Wang, G and Jonika, MM and Gill, CA and Blackmon, H and Athrey, GN}, title = {A Primer for Single-Cell Sequencing in Non-Model Organisms.}, journal = {Genes}, volume = {13}, number = {2}, pages = {}, pmid = {35205423}, issn = {2073-4425}, support = {R35 GM138098/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Genotype ; *Phenotype ; }, abstract = {Single-cell sequencing technologies have led to a revolution in our knowledge of the diversity of cell types, connections between biological levels of organization, and relationships between genotype and phenotype. These advances have mainly come from using model organisms; however, using single-cell sequencing in non-model organisms could enable investigations of questions inaccessible with typical model organisms. This primer describes a general workflow for single-cell sequencing studies and considerations for using non-model organisms (limited to multicellular animals). Importantly, single-cell sequencing, when further applied in non-model organisms, will allow for a deeper understanding of the mechanisms between genotype and phenotype and the basis for biological variation.}, } @article {pmid35194081, year = {2022}, author = {Lin, HK and Cheng, JH and Wu, CC and Hsieh, FS and Dunlap, C and Chen, SH}, title = {Functional buffering via cell-specific gene expression promotes tissue homeostasis and cancer robustness.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {2974}, pmid = {35194081}, issn = {2045-2322}, mesh = {*Databases, Nucleic Acid ; *Gene Expression Regulation, Neoplastic ; *Homeostasis ; Humans ; *Neoplasms/genetics/metabolism ; Organ Specificity ; }, abstract = {Functional buffering that ensures biological robustness is critical for maintaining tissue homeostasis, organismal survival, and evolution of novelty. However, the mechanism underlying functional buffering, particularly in multicellular organisms, remains largely elusive. Here, we proposed that functional buffering can be mediated via expression of buffering genes in specific cells and tissues, by which we named Cell-specific Expression-BUffering (CEBU). We developed an inference index (C-score) for CEBU by computing C-scores across 684 human cell lines using genome-wide CRISPR screens and transcriptomic RNA-seq. We report that C-score-identified putative buffering gene pairs are enriched for members of the same duplicated gene family, pathway, and protein complex. Furthermore, CEBU is especially prevalent in tissues of low regenerative capacity (e.g., bone and neuronal tissues) and is weakest in highly regenerative blood cells, linking functional buffering to tissue regeneration. Clinically, the buffering capacity enabled by CEBU can help predict patient survival for multiple cancers. Our results suggest CEBU as a potential buffering mechanism contributing to tissue homeostasis and cancer robustness in humans.}, } @article {pmid35189700, year = {2022}, author = {Simon-Soro, A and Ren, Z and Krom, BP and Hoogenkamp, MA and Cabello-Yeves, PJ and Daniel, SG and Bittinger, K and Tomas, I and Koo, H and Mira, A}, title = {Polymicrobial Aggregates in Human Saliva Build the Oral Biofilm.}, journal = {mBio}, volume = {13}, number = {1}, pages = {e0013122}, pmid = {35189700}, issn = {2150-7511}, support = {R01 DE025220/DE/NIDCR NIH HHS/United States ; 834.13.006//NWO Earth and Life Sciences (ALW)/ ; BIO2015-68711-R//Spanish Ministry of Economy and Competitiveness/ ; }, mesh = {Bacteria ; Biofilms ; *Ecosystem ; Humans ; Phylogeny ; *Saliva/microbiology ; }, abstract = {Biofilm community development has been established as a sequential process starting from the attachment of single cells on a surface. However, microorganisms are often found as aggregates in the environment and in biological fluids. Here, we conduct a comprehensive analysis of the native structure and composition of aggregated microbial assemblages in human saliva and investigate their spatiotemporal attachment and biofilm community development. Using multiscale imaging, cell sorting, and computational approaches combined with sequencing analysis, a diverse mixture of aggregates varying in size, structure, and microbial composition, including bacteria associated with host epithelial cells, can be found in saliva in addition to a few single-cell forms. Phylogenetic analysis reveals a mixture of complex consortia of aerobes and anaerobes in which bacteria traditionally considered early and late colonizers are found mixed together. When individually tracked during colonization and biofilm initiation, aggregates rapidly proliferate and expand tridimensionally, modulating population growth, spatial organization, and community scaffolding. In contrast, most single cells remain static or are incorporated by actively growing aggregates. These results suggest an alternative biofilm development process whereby aggregates containing different species or associated with human cells collectively adhere to the surface as "growth nuclei" to build the biofilm and shape polymicrobial communities at various spatial and taxonomic scales. IMPORTANCE Microbes in biological fluids can be found as aggregates. How these multicellular structures bind to surfaces and initiate the biofilm life cycle remains understudied. Here, we investigate the structural organization of microbial aggregates in human saliva and their role in biofilm formation. We found diverse mixtures of aggregates with different sizes, structures, and compositions in addition to free-living cells. When individually tracked during binding and growth on tooth-like surfaces, most aggregates developed into structured biofilm communities, whereas most single cells remained static or were engulfed by the growing aggregates. Our results reveal that preformed microbial consortia adhere as "buds of growth," governing biofilm initiation without specific taxonomic order or cell-by-cell succession, which provide new insights into spatial and population heterogeneity development in complex ecosystems.}, } @article {pmid35188101, year = {2022}, author = {Day, TC and Höhn, SS and Zamani-Dahaj, SA and Yanni, D and Burnetti, A and Pentz, J and Honerkamp-Smith, AR and Wioland, H and Sleath, HR and Ratcliff, WC and Goldstein, RE and Yunker, PJ}, title = {Cellular organization in lab-evolved and extant multicellular species obeys a maximum entropy law.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35188101}, issn = {2050-084X}, support = {/WT_/Wellcome Trust/United Kingdom ; 207510/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; R35 GM138030/GM/NIGMS NIH HHS/United States ; R35 GM138354/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Size ; *Directed Molecular Evolution ; Phylogeny ; Volvox/cytology/*genetics/physiology ; Yeasts/cytology/*genetics/physiology ; }, abstract = {The prevalence of multicellular organisms is due in part to their ability to form complex structures. How cells pack in these structures is a fundamental biophysical issue, underlying their functional properties. However, much remains unknown about how cell packing geometries arise, and how they are affected by random noise during growth - especially absent developmental programs. Here, we quantify the statistics of cellular neighborhoods of two different multicellular eukaryotes: lab-evolved 'snowflake' yeast and the green alga Volvox carteri. We find that despite large differences in cellular organization, the free space associated with individual cells in both organisms closely fits a modified gamma distribution, consistent with maximum entropy predictions originally developed for granular materials. This 'entropic' cellular packing ensures a degree of predictability despite noise, facilitating parent-offspring fidelity even in the absence of developmental regulation. Together with simulations of diverse growth morphologies, these results suggest that gamma-distributed cell neighborhood sizes are a general feature of multicellularity, arising from conserved statistics of cellular packing.}, } @article {pmid35186015, year = {2021}, author = {Zeng, Q and Liu, H and Chu, X and Niu, Y and Wang, C and Markov, GV and Teng, L}, title = {Independent Evolution of the MYB Family in Brown Algae.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {811993}, pmid = {35186015}, issn = {1664-8021}, abstract = {Myeloblastosis (MYB) proteins represent one of the largest families of eukaryotic transcription factors and regulate important processes in growth and development. Studies on MYBs have mainly focused on animals and plants; however, comprehensive analysis across other supergroups such as SAR (stramenopiles, alveolates, and rhizarians) is lacking. This study characterized the structure, evolution, and expression of MYBs in four brown algae, which comprise the biggest multicellular lineage of SAR. Subfamily 1R-MYB comprised heterogeneous proteins, with fewer conserved motifs found outside the MYB domain. Unlike the SHAQKY subgroup of plant 1R-MYB, THAQKY comprised the largest subgroup of brown algal 1R-MYBs. Unlike the expansion of 2R-MYBs in plants, brown algae harbored more 3R-MYBs than 2R-MYBs. At least ten 2R-MYBs, fifteen 3R-MYBs, and one 6R-MYB orthologs existed in the common ancestor of brown algae. Phylogenetic analysis showed that brown algal MYBs had ancient origins and a diverged evolution. They showed strong affinity with stramenopile species, while not with red algae, green algae, or animals, suggesting that brown algal MYBs did not come from the secondary endosymbiosis of red and green plastids. Sequence comparison among all repeats of the three types of MYB subfamilies revealed that the repeat of 1R-MYBs showed higher sequence identity with the R3 of 2R-MYBs and 3R-MYBs, which supports the idea that 1R-MYB was derived from loss of the first and second repeats of the ancestor MYB. Compared with other species of SAR, brown algal MYB proteins exhibited a higher proportion of intrinsic disordered regions, which might contribute to multicellular evolution. Expression analysis showed that many MYB genes are responsive to different stress conditions and developmental stages. The evolution and expression analyses provided a comprehensive analysis of the phylogeny and functions of MYBs in brown algae.}, } @article {pmid35175900, year = {2022}, author = {Milocco, L and Salazar-Ciudad, I}, title = {Evolution of the G Matrix under Nonlinear Genotype-Phenotype Maps.}, journal = {The American naturalist}, volume = {199}, number = {3}, pages = {420-435}, doi = {10.1086/717814}, pmid = {35175900}, issn = {1537-5323}, mesh = {*Biological Evolution ; Evolution, Molecular ; Genetic Variation ; *Genetics, Population ; Genotype ; Models, Genetic ; Phenotype ; Selection, Genetic ; }, abstract = {AbstractThe G matrix is a statistical summary of the genetic basis of a set of traits and a central pillar of quantitative genetics. A persistent controversy is whether G changes slowly or quickly over time. The evolution of G is important because it affects the ability to predict, or reconstruct, evolution by selection. Empirical studies have found mixed results on how fast G evolves. Theoretical work has largely been developed under the assumption that the relationship between genetic variation and phenotypic variation-the genotype-phenotype map (GPM)-is linear. Under this assumption, G is expected to remain constant over long periods of time. However, according to developmental biology, the GPM is typically complex and nonlinear. Here, we use a GPM model based on the development of a multicellular organ to study how G evolves. We find that G can change relatively fast and in qualitative different ways, which we describe in detail. Changes can be particularly large when the population crosses between regions of the GPM that have different properties. This can result in the additive genetic variance in the direction of selection fluctuating over time and even increasing despite the eroding effect of selection.}, } @article {pmid35170314, year = {2022}, author = {Kulkarni, P and Bhattacharya, S and Achuthan, S and Behal, A and Jolly, MK and Kotnala, S and Mohanty, A and Rangarajan, G and Salgia, R and Uversky, V}, title = {Intrinsically Disordered Proteins: Critical Components of the Wetware.}, journal = {Chemical reviews}, volume = {122}, number = {6}, pages = {6614-6633}, pmid = {35170314}, issn = {1520-6890}, support = {P30 CA033572/CA/NCI NIH HHS/United States ; }, mesh = {*Intrinsically Disordered Proteins/chemistry ; Organelles/chemistry ; Protein Conformation ; Protein Interaction Maps ; }, abstract = {Despite the wealth of knowledge gained about intrinsically disordered proteins (IDPs) since their discovery, there are several aspects that remain unexplored and, hence, poorly understood. A living cell is a complex adaptive system that can be described as a wetware─a metaphor used to describe the cell as a computer comprising both hardware and software and attuned to logic gates─capable of "making" decisions. In this focused Review, we discuss how IDPs, as critical components of the wetware, influence cell-fate decisions by wiring protein interaction networks to keep them minimally frustrated. Because IDPs lie between order and chaos, we explore the possibility that they can be modeled as attractors. Further, we discuss how the conformational dynamics of IDPs manifests itself as conformational noise, which can potentially amplify transcriptional noise to stochastically switch cellular phenotypes. Finally, we explore the potential role of IDPs in prebiotic evolution, in forming proteinaceous membrane-less organelles, in the origin of multicellularity, and in protein conformation-based transgenerational inheritance of acquired characteristics. Together, these ideas provide a new conceptual framework to discern how IDPs may perform critical biological functions despite their lack of structure.}, } @article {pmid35167804, year = {2022}, author = {Davis, JR and Ainslie, AP and Williamson, JJ and Ferreira, A and Torres-Sánchez, A and Hoppe, A and Mangione, F and Smith, MB and Martin-Blanco, E and Salbreux, G and Tapon, N}, title = {ECM degradation in the Drosophila abdominal epidermis initiates tissue growth that ceases with rapid cell-cycle exit.}, journal = {Current biology : CB}, volume = {32}, number = {6}, pages = {1285-1300.e4}, pmid = {35167804}, issn = {1879-0445}, support = {FC001175/MRC_/Medical Research Council/United Kingdom ; FC001317/WT_/Wellcome Trust/United Kingdom ; 107885/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; FC001175/WT_/Wellcome Trust/United Kingdom ; FC001175/ARC_/Arthritis Research UK/United Kingdom ; FC001317/ARC_/Arthritis Research UK/United Kingdom ; FC001317/CRUK_/Cancer Research UK/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; FC001317/MRC_/Medical Research Council/United Kingdom ; FC001175/CRUK_/Cancer Research UK/United Kingdom ; 201358/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Cycle ; Cell Division ; *Drosophila ; *Epidermal Cells ; Epidermis ; Mice ; }, abstract = {During development, multicellular organisms undergo stereotypical patterns of tissue growth in space and time. How developmental growth is orchestrated remains unclear, largely due to the difficulty of observing and quantitating this process in a living organism. Drosophila histoblast nests are small clusters of progenitor epithelial cells that undergo extensive growth to give rise to the adult abdominal epidermis and are amenable to live imaging. Our quantitative analysis of histoblast proliferation and tissue mechanics reveals that tissue growth is driven by cell divisions initiated through basal extracellular matrix degradation by matrix metalloproteases secreted by the neighboring larval epidermal cells. Laser ablations and computational simulations show that tissue mechanical tension does not decrease as the histoblasts fill the abdominal epidermal surface. During tissue growth, the histoblasts display oscillatory cell division rates until growth termination occurs through the rapid emergence of G0/G1 arrested cells, rather than a gradual increase in cell-cycle time as observed in other systems such as the Drosophila wing and mouse postnatal epidermis. Different developing tissues can therefore achieve their final size using distinct growth termination strategies. Thus, adult abdominal epidermal development is characterized by changes in the tissue microenvironment and a rapid exit from the cell cycle.}, } @article {pmid35159213, year = {2022}, author = {Ribba, AS and Fraboulet, S and Sadoul, K and Lafanechère, L}, title = {The Role of LIM Kinases during Development: A Lens to Get a Glimpse of Their Implication in Pathologies.}, journal = {Cells}, volume = {11}, number = {3}, pages = {}, pmid = {35159213}, issn = {2073-4409}, support = {R18LAFANECHERE//Ligue contre le Cancer, comité de l'Isère/ ; }, mesh = {Actin Depolymerizing Factors/metabolism ; Animals ; *Lim Kinases/metabolism ; Phosphorylation ; Phylogeny ; *Protein Kinases/metabolism ; }, abstract = {The organization of cell populations within animal tissues is essential for the morphogenesis of organs during development. Cells recognize three-dimensional positions with respect to the whole organism and regulate their cell shape, motility, migration, polarization, growth, differentiation, gene expression and cell death according to extracellular signals. Remodeling of the actin filaments is essential to achieve these cell morphological changes. Cofilin is an important binding protein for these filaments; it increases their elasticity in terms of flexion and torsion and also severs them. The activity of cofilin is spatiotemporally inhibited via phosphorylation by the LIM domain kinases 1 and 2 (LIMK1 and LIMK2). Phylogenetic analysis indicates that the phospho-regulation of cofilin has evolved as a mechanism controlling the reorganization of the actin cytoskeleton during complex multicellular processes, such as those that occur during embryogenesis. In this context, the main objective of this review is to provide an update of the respective role of each of the LIM kinases during embryonic development.}, } @article {pmid35154170, year = {2021}, author = {Žárský, J and Žárský, V and Hanáček, M and Žárský, V}, title = {Cryogenian Glacial Habitats as a Plant Terrestrialisation Cradle - The Origin of the Anydrophytes and Zygnematophyceae Split.}, journal = {Frontiers in plant science}, volume = {12}, number = {}, pages = {735020}, pmid = {35154170}, issn = {1664-462X}, abstract = {For tens of millions of years (Ma), the terrestrial habitats of Snowball Earth during the Cryogenian period (between 720 and 635 Ma before present-Neoproterozoic Era) were possibly dominated by global snow and ice cover up to the equatorial sublimative desert. The most recent time-calibrated phylogenies calibrated not only on plants but on a comprehensive set of eukaryotes indicate that within the Streptophyta, multicellular charophytes (Phragmoplastophyta) evolved in the Mesoproterozoic to the early Neoproterozoic. At the same time, Cryogenian is the time of the likely origin of the common ancestor of Zygnematophyceae and Embryophyta and later, also of the Zygnematophyceae-Embryophyta split. This common ancestor is proposed to be called Anydrophyta; here, we use anydrophytes. Based on the combination of published phylogenomic studies and estimated diversification time comparisons, we deem it highly likely that anydrophytes evolved in response to Cryogenian cooling. Also, later in the Cryogenian, secondary simplification of multicellular anydrophytes and loss of flagella resulted in Zygnematophyceae diversification as an adaptation to the extended cold glacial environment. We propose that the Marinoan geochemically documented expansion of first terrestrial flora has been represented not only by Chlorophyta but also by Streptophyta, including the anydrophytes, and later by Zygnematophyceae, thriving on glacial surfaces until today. It is possible that multicellular early Embryophyta survived in less abundant (possibly relatively warmer) refugia, relying more on mineral substrates, allowing the retention of flagella-based sexuality. The loss of flagella and sexual reproduction by conjugation evolved in Zygnematophyceae and zygomycetous fungi during the Cryogenian in a remarkably convergent way. Thus, we support the concept that the important basal cellular adaptations to terrestrial environments were exapted in streptophyte algae for terrestrialization and propose that this was stimulated by the adaptation to glacial habitats dominating the Cryogenian Snowball Earth. Including the glacial lifestyle when considering the rise of land plants increases the parsimony of connecting different ecological, phylogenetic, and physiological puzzles of the journey from aquatic algae to terrestrial floras.}, } @article {pmid35143662, year = {2022}, author = {Benzerara, K and Duprat, E and Bitard-Feildel, T and Caumes, G and Cassier-Chauvat, C and Chauvat, F and Dezi, M and Diop, SI and Gaschignard, G and Görgen, S and Gugger, M and López-García, P and Millet, M and Skouri-Panet, F and Moreira, D and Callebaut, I}, title = {A New Gene Family Diagnostic for Intracellular Biomineralization of Amorphous Ca Carbonates by Cyanobacteria.}, journal = {Genome biology and evolution}, volume = {14}, number = {3}, pages = {}, pmid = {35143662}, issn = {1759-6653}, mesh = {*Biomineralization/genetics ; Calcium Carbonate/metabolism ; Carbonates/metabolism ; *Cyanobacteria/metabolism ; Phylogeny ; }, abstract = {Cyanobacteria have massively contributed to carbonate deposition over the geological history. They are traditionally thought to biomineralize CaCO3 extracellularly as an indirect byproduct of photosynthesis. However, the recent discovery of freshwater cyanobacteria-forming intracellular amorphous calcium carbonates (iACC) challenges this view. Despite the geochemical interest of such a biomineralization process, its molecular mechanisms and evolutionary history remain elusive. Here, using comparative genomics, we identify a new gene (ccyA) and protein family (calcyanin) possibly associated with cyanobacterial iACC biomineralization. Proteins of the calcyanin family are composed of a conserved C-terminal domain, which likely adopts an original fold, and a variable N-terminal domain whose structure allows differentiating four major types among the 35 known calcyanin homologs. Calcyanin lacks detectable full-length homologs with known function. The overexpression of ccyA in iACC-lacking cyanobacteria resulted in an increased intracellular Ca content. Moreover, ccyA presence was correlated and/or colocalized with genes involved in Ca or HCO3- transport and homeostasis, supporting the hypothesis of a functional role of calcyanin in iACC biomineralization. Whatever its function, ccyA appears as diagnostic of intracellular calcification in cyanobacteria. By searching for ccyA in publicly available genomes, we identified 13 additional cyanobacterial strains forming iACC, as confirmed by microscopy. This extends our knowledge about the phylogenetic and environmental distribution of cyanobacterial iACC biomineralization, especially with the detection of multicellular genera as well as a marine species. Moreover, ccyA was probably present in ancient cyanobacteria, with independent losses in various lineages that resulted in a broad but patchy distribution across modern cyanobacteria.}, } @article {pmid35143488, year = {2022}, author = {Yaguchi, S and Taniguchi, Y and Suzuki, H and Kamata, M and Yaguchi, J}, title = {Planktonic sea urchin larvae change their swimming direction in response to strong photoirradiation.}, journal = {PLoS genetics}, volume = {18}, number = {2}, pages = {e1010033}, pmid = {35143488}, issn = {1553-7404}, mesh = {Animals ; Cilia/metabolism ; Larva/metabolism ; Light ; Locomotion/physiology ; Movement/*physiology ; Muscles/physiology ; Opsins/genetics/metabolism ; Photoreceptor Cells/*metabolism ; Plankton ; Sea Urchins/*metabolism ; }, abstract = {To survive, organisms need to precisely respond to various environmental factors, such as light and gravity. Among these, light is so important for most life on Earth that light-response systems have become extraordinarily developed during evolution, especially in multicellular animals. A combination of photoreceptors, nervous system components, and effectors allows these animals to respond to light stimuli. In most macroscopic animals, muscles function as effectors responding to light, and in some microscopic aquatic animals, cilia play a role. It is likely that the cilia-based response was the first to develop and that it has been substituted by the muscle-based response along with increases in body size. However, although the function of muscle appears prominent, it is poorly understood whether ciliary responses to light are present and/or functional, especially in deuterostomes, because it is possible that these responses are too subtle to be observed, unlike muscle responses. Here, we show that planktonic sea urchin larvae reverse their swimming direction due to the inhibitory effect of light on the cholinergic neuron signaling>forward swimming pathway. We found that strong photoirradiation of larvae that stay on the surface of seawater immediately drives the larvae away from the surface due to backward swimming. When Opsin2, which is expressed in mesenchymal cells in larval arms, is knocked down, the larvae do not show backward swimming under photoirradiation. Although Opsin2-expressing cells are not neuronal cells, immunohistochemical analysis revealed that they directly attach to cholinergic neurons, which are thought to regulate forward swimming. These data indicate that light, through Opsin2, inhibits the activity of cholinergic signaling, which normally promotes larval forward swimming, and that the light-dependent ciliary response is present in deuterostomes. These findings shed light on how light-responsive tissues/organelles have been conserved and diversified during evolution.}, } @article {pmid35135345, year = {2022}, author = {La Richelière, F and Muñoz, G and Guénard, B and Dunn, RR and Economo, EP and Powell, S and Sanders, NJ and Weiser, MD and Abouheif, E and Lessard, JP}, title = {Warm and arid regions of the world are hotspots of superorganism complexity.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1968}, pages = {20211899}, pmid = {35135345}, issn = {1471-2954}, mesh = {Animals ; *Ants/genetics ; Desert Climate ; Neurons ; Phenotype ; }, abstract = {Biologists have long been fascinated by the processes that give rise to phenotypic complexity of organisms, yet whether there exist geographical hotspots of phenotypic complexity remains poorly explored. Phenotypic complexity can be readily observed in ant colonies, which are superorganisms with morphologically differentiated queen and worker castes analogous to the germline and soma of multicellular organisms. Several ant species have evolved 'worker polymorphism', where workers in a single colony show quantifiable differences in size and head-to-body scaling. Here, we use 256 754 occurrence points from 8990 ant species to investigate the geography of worker polymorphism. We show that arid regions of the world are the hotspots of superorganism complexity. Tropical savannahs and deserts, which are typically species-poor relative to tropical or even temperate forests, harbour the highest densities of polymorphic ants. We discuss the possible adaptive advantages that worker polymorphism provides in arid environments. Our work may provide a window into the environmental conditions that promote the emergence of highly complex phenotypes.}, } @article {pmid35107212, year = {2023}, author = {Nishizawa, H and Yamanaka, M and Igarashi, K}, title = {Ferroptosis: regulation by competition between NRF2 and BACH1 and propagation of the death signal.}, journal = {The FEBS journal}, volume = {290}, number = {7}, pages = {1688-1704}, doi = {10.1111/febs.16382}, pmid = {35107212}, issn = {1742-4658}, mesh = {Humans ; Basic-Leucine Zipper Transcription Factors/genetics/metabolism ; *Ferroptosis/genetics ; Iron/metabolism ; *Neoplasms ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress ; }, abstract = {Ferroptosis is triggered by a chain of intracellular labile iron-dependent peroxidation of cell membrane phospholipids. Ferroptosis is important not only as a cause of ischaemic and neurodegenerative diseases but also as a mechanism of cancer suppression, and a better understanding of its regulatory mechanism is required. It has become clear that ferroptosis is finely controlled by two oxidative stress-responsive transcription factors, NRF2 (NF-E2-related factor 2) and BACH1 (BTB and CNC homology 1). NRF2 and BACH1 inhibit and promote ferroptosis, respectively, by activating or suppressing the expression of genes in the major regulatory pathways of ferroptosis: intracellular labile iron metabolism, the GSH (glutathione) -GPX4 (glutathione peroxidase 4) pathway and the FSP1 (ferroptosis suppressor protein 1)-CoQ (coenzyme Q) pathway. In addition to this, NRF2 and BACH1 control ferroptosis through the regulation of lipid metabolism and cell differentiation. This multifaceted regulation of ferroptosis by NRF2 and BACH1 is considered to have been acquired during the evolution of multicellular organisms, allowing the utilization of ferroptosis for maintaining homeostasis, including cancer suppression. In terms of cell-cell interaction, it has been revealed that ferroptosis has the property of propagating to surrounding cells along with lipid peroxidation. The regulation of ferroptosis by NRF2 and BACH1 and the propagation phenomenon could be used to realize anticancer cell therapy in the future. In this review, these points will be summarized and discussed.}, } @article {pmid35078543, year = {2022}, author = {Purschke, G and Vodopyanov, S and Baller, A and von Palubitzki, T and Bartolomaeus, T and Beckers, P}, title = {Ultrastructure of cerebral eyes in Oweniidae and Chaetopteridae (Annelida) - implications for the evolution of eyes in Annelida.}, journal = {Zoological letters}, volume = {8}, number = {1}, pages = {3}, pmid = {35078543}, issn = {2056-306X}, support = {Ostpartnerschaften; Vladimir Vernadskij Programm//deutscher akademischer austauschdienst/ ; }, abstract = {BACKGROUND: Recent phylogenomic studies have revealed a robust, new hypothesis of annelid phylogeny. Most surprisingly, a few early branching lineages formed a basal grade, whereas the majority of taxa were categorized as monophyletic Pleistoannelida. Members of these basal groups show a comparatively simple organization lacking certain characters regarded to be annelid specific. Thus, the evolution of organ systems and the characteristics probably present in the last common annelid ancestor require reevaluation. With respect to light-sensitive organs, a pair of simple larval eyes is regarded as being present in their last common ancestor. However, the evolutionary origin and structure of adult eyes remain obscure. Typically, adult eyes are multicellular pigment cups or pinhole eyes with or without a lens comprising rhabdomeric photoreceptor cells (PRCs) and pigmented supportive cells (PSCs) in converse design. However, in the most basal lineages, eyes are only present in a few taxa, and thus far, their ultrastructure is unknown.

RESULTS: Ultrastructural investigations of members of Oweniidae and Chaetopteridae reveal a corresponding design of adult cerebral eyes and PRCs. The eyes in species of these groups are simple pigment spot eyes, either forming a flat patch or embedded in a tube-like invagination. They are part of the epidermis and comprise two cell types, PSCs and rhabdomeric PRCs. Both cell types bear microvilli and one more or less reduced cilium. However, the PRCs showed only a moderate increase in the apical membrane surface in the form of irregularly arranged microvilli intermingling with those of the PSCs; a densely arranged brush border of rhabdomeric microvilli was absent. Additionally, both cell types show certain characteristics elsewhere observable in typical epidermal supportive cells.

CONCLUSIONS: These findings shed new light on the evolutionary history of adult eyes in Annelida. Most likely, the adult eye of the annelid stem species was a pair of simple pigment spot eyes with only slightly specialized PSCs and PRCs being an integrative part of the epidermis. As is the case for the nuchal organs, typical pigment cup adult eyes presumably evolved later in the annelid phylogeny, namely, in the stem lineages of Amphinomida and Pleistoannelida.}, } @article {pmid35056939, year = {2021}, author = {Shipunova, VO and Kovalenko, VL and Kotelnikova, PA and Sogomonyan, AS and Shilova, ON and Komedchikova, EN and Zvyagin, AV and Nikitin, MP and Deyev, SM}, title = {Targeting Cancer Cell Tight Junctions Enhances PLGA-Based Photothermal Sensitizers' Performance In Vitro and In Vivo.}, journal = {Pharmaceutics}, volume = {14}, number = {1}, pages = {}, pmid = {35056939}, issn = {1999-4923}, support = {21-74-30016//Russian Science Foundation/ ; 19-29-04012//Russian Foundation for Basic Research/ ; N/A//Subsidy of Sirius University/ ; }, abstract = {The development of non-invasive photothermal therapy (PTT) methods utilizing nanoparticles as sensitizers is one of the most promising directions in modern oncology. Nanoparticles loaded with photothermal dyes are capable of delivering a sufficient amount of a therapeutic substance and releasing it with the desired kinetics in vivo. However, the effectiveness of oncotherapy methods, including PTT, is often limited due to poor penetration of sensitizers into the tumor, especially into solid tumors of epithelial origin characterized by tight cellular junctions. In this work, we synthesized 200 nm nanoparticles from the biocompatible copolymer of lactic and glycolic acid, PLGA, loaded with magnesium phthalocyanine, PLGA/Pht-Mg. The PLGA/Pht-Mg particles under the irradiation with NIR light (808 nm), heat the surrounding solution by 40 °C. The effectiveness of using such particles for cancer cells elimination was demonstrated in 2D culture in vitro and in our original 3D model with multicellular spheroids possessing tight cell contacts. It was shown that the mean inhibitory concentration of such nanoparticles upon light irradiation for 15 min worsens by more than an order of magnitude: IC50 increases from 3 µg/mL for 2D culture vs. 117 µg/mL for 3D culture. However, when using the JO-4 intercellular junction opener protein, which causes a short epithelial-mesenchymal transition and transiently opens intercellular junctions in epithelial cells, the efficiency of nanoparticles in 3D culture was comparable or even outperforming that for 2D (IC50 = 1.9 µg/mL with JO-4). Synergy in the co-administration of PTT nanosensitizers and JO-4 protein was found to retain in vivo using orthotopic tumors of BALB/c mice: we demonstrated that the efficiency in the delivery of such nanoparticles to the tumor is 2.5 times increased when PLGA/Pht-Mg nanoparticles are administered together with JO-4. Thus the targeting the tumor cell junctions can significantly increase the performance of PTT nanosensitizers.}, } @article {pmid35054440, year = {2021}, author = {Alekseev, VR and Hwang, JS and Levinskikh, MA}, title = {Effect of Space Flight Factor on Dormant Stages in Aquatic Organisms: A Review of International Space Station and Terrestrial Experiments.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {35054440}, issn = {2075-1729}, support = {1021051403065-4//Russian Government Programme/ ; AAAAA19- 119020690091-0//Russian Government Programme/ ; }, abstract = {This work is a review of the experiments carried out in the Russian segment of the ISS (inside and outside) from 2005 to 2016 on the effect of the space flight factor on the resting stages of organisms. In outer space, ultraviolet, a wide range of high and low temperatures, cosmic radiation, altered gravity, modified electromagnetic field, vacuum, factors of technical origin, ultrasound, microwave radiation, etc. and their combination determine the damaging effect on living organisms. At the same time, biological dormancy, known in a wide range of bacteria, fungi, animals and plants, allows them to maintain the viability of their dormant stages in extreme conditions for a long time, which possibly allows them to survive during space flight. From 2005 to 2016, the resting stages (propagules) of micro- and multicellular organisms were tested on the ISS to assess their ability to survive after prolonged exposure to the conditions of open space and space flight. Among the more than 40 species studied, about a third were dormant stages of aquatic organisms (eggs of cyprinodont fish, daphnia embryos, resting eggs of fairy shrimps, tadpole shrimps, copepods and ostracods, diapausing larvae of dipterans, as well as resting cysts of algae). The experiments were carried out within the framework of four research programs: (1) inside the ISS with a limited set of investigated species (Akvarium program); (2) outside the station in outer space without exposure to ultraviolet radiation (Biorisk program); (3) under modified space conditions simulating the surface of Mars (Expose program); and (4) in an Earth-based laboratory where single-factor experiments were carried out with neutron radiation, modified magnetic field, microwave radiation and ultrasound. Fundamentally new data were obtained on the stability of the resting stages of aquatic organisms exposed to the factors of the space environment, which modified the idea of the possibility of bringing Earth life forms to other planets with spacecraft and astronauts. It also can be used for creating an extraterrestrial artificial ecosystem and searching for extraterrestrial life.}, } @article {pmid35053310, year = {2022}, author = {Shevyrev, D and Tereshchenko, V and Kozlov, V and Sennikov, S}, title = {Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets.}, journal = {Cells}, volume = {11}, number = {2}, pages = {}, pmid = {35053310}, issn = {2073-4409}, support = {21-75-10089//Russian Science Foundation/ ; }, mesh = {Evolution, Molecular ; Humans ; Peptides/metabolism ; *Phylogeny ; T-Lymphocyte Subsets/*metabolism ; Transcription Factors/*chemistry/classification/*metabolism ; Transcriptome/genetics ; }, abstract = {It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeostasis, supports multicellularity, and protects an organism from different pathogens at a qualitatively different level than innate immunity. This seemingly simple property is based on millions of years of evolution that led to the formation of diversification mechanisms of antigen-recognizing receptors and later to the emergence of a system of presentation of the self and non-self antigens. The latter could have a crucial significance because the presentation of nearly complete diversity of auto-antigens in the thymus allows for the "calibration" of the forming repertoires of T-cells for the recognition of self, altered-self, and non-self antigens that are presented on the periphery. The central role in this process belongs to promiscuous gene expression by the thymic epithelial cells that express nearly the whole spectrum of proteins encoded in the genome, meanwhile maintaining their cellular identity. This complex mechanism requires strict control that is executed by several transcription factors. One of the most important of them is AIRE. This noncanonical transcription factor not only regulates the processes of differentiation and expression of peripheral tissue-specific antigens in the thymic medullar epithelial cells but also controls intercellular interactions in the thymus. Besides, it participates in an increase in the diversity and transfer of presented antigens and thus influences the formation of repertoires of maturing thymocytes. Due to these complex effects, AIRE is also called a transcriptional regulator. In this review, we briefly described the history of AIRE discovery, its structure, functions, and role in the formation of antigen-recognizing receptor repertoires, along with other transcription factors. We focused on the phylogenetic prerequisites for the development of modern adaptive immunity and emphasized the importance of the antigen presentation system.}, } @article {pmid35051729, year = {2022}, author = {Masqué-Soler, N and Gehrung, M and Kosmidou, C and Li, X and Diwan, I and Rafferty, C and Atabakhsh, E and Markowetz, F and Fitzgerald, RC}, title = {Computational pathology aids derivation of microRNA biomarker signals from Cytosponge samples.}, journal = {EBioMedicine}, volume = {76}, number = {}, pages = {103814}, pmid = {35051729}, issn = {2352-3964}, support = {MR/W014122/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Artificial Intelligence ; *Barrett Esophagus/genetics ; Biomarkers/metabolism ; Cross-Sectional Studies ; *Esophageal Neoplasms/diagnosis/genetics/pathology ; Humans ; *MicroRNAs/genetics ; }, abstract = {BACKGROUND: Non-endoscopic cell collection devices combined with biomarkers can detect Barrett's intestinal metaplasia and early oesophageal cancer. However, assays performed on multi-cellular samples lose information about the cell source of the biomarker signal. This cross-sectional study examines whether a bespoke artificial intelligence-based computational pathology tool could ascertain the cellular origin of microRNA biomarkers, to inform interpretation of the disease pathology, and confirm biomarker validity.

METHODS: The microRNA expression profiles of 110 targets were assessed with a custom multiplexed panel in a cohort of 117 individuals with reflux that took a Cytosponge test. A computational pathology tool quantified the amount of columnar epithelium present in pathology slides, and results were correlated with microRNA signals. An independent cohort of 139 Cytosponges, each from an individual patient, was used to validate the findings via qPCR.

FINDINGS: Seventeen microRNAs are upregulated in BE compared to healthy squamous epithelia, of which 13 remain upregulated in dysplasia. A pathway enrichment analysis confirmed association to neoplastic and cell cycle regulation processes. Ten microRNAs positively correlated with columnar epithelium content, with miRNA-192-5p and -194-5p accurately detecting the presence of gastric cells (AUC 0.97 and 0.95). In contrast, miR-196a-5p is confirmed as a specific BE marker.

INTERPRETATION: Computational pathology tools aid accurate cellular attribution of molecular signals. This innovative design with multiplex microRNA coupled with artificial intelligence has led to discovery of a quality control metric suitable for large scale application of the Cytosponge. Similar approaches could aid optimal interpretation of biomarkers for clinical use.

FUNDING: Funded by the NIHR Cambridge Biomedical Research Centre, the Medical Research Council, the Rosetrees and Stoneygate Trusts, and CRUK core grants.}, } @article {pmid35032334, year = {2022}, author = {Nemec-Venza, Z and Madden, C and Stewart, A and Liu, W and Novák, O and Pěnčík, A and Cuming, AC and Kamisugi, Y and Harrison, CJ}, title = {CLAVATA modulates auxin homeostasis and transport to regulate stem cell identity and plant shape in a moss.}, journal = {The New phytologist}, volume = {234}, number = {1}, pages = {149-163}, pmid = {35032334}, issn = {1469-8137}, mesh = {*Arabidopsis Proteins/genetics/metabolism ; *Bryophyta/metabolism ; *Bryopsida/genetics/metabolism ; Gene Expression Regulation, Plant ; Homeostasis ; Indoleacetic Acids/metabolism ; Stem Cells/metabolism ; }, abstract = {The CLAVATA pathway is a key regulator of stem cell function in the multicellular shoot tips of Arabidopsis, where it acts via the WUSCHEL transcription factor to modulate hormone homeostasis. Broad-scale evolutionary comparisons have shown that CLAVATA is a conserved regulator of land plant stem cell function, but CLAVATA acts independently of WUSCHEL-like (WOX) proteins in bryophytes. The relationship between CLAVATA, hormone homeostasis and the evolution of land plant stem cell functions is unknown. Here we show that in the moss, Physcomitrella (Physcomitrium patens), CLAVATA affects stem cell activity by modulating hormone homeostasis. CLAVATA pathway genes are expressed in the tip cells of filamentous tissues, regulating cell identity, filament branching, plant spread and auxin synthesis. The receptor-like kinase PpRPK2 plays the major role, and Pprpk2 mutants have abnormal responses to cytokinin, auxin and auxin transport inhibition, and show reduced expression of PIN auxin transporters. We propose a model whereby PpRPK2 modulates auxin gradients in filaments to determine stem cell identity and overall plant form. Our data indicate that CLAVATA-mediated auxin homeostasis is a fundamental property of plant stem cell function, probably exhibited by the last shared common ancestor of land plants.}, } @article {pmid35023778, year = {2022}, author = {Ji, R and Zhang, W and Pan, Y and Lin, W}, title = {MagCluster: a Tool for Identification, Annotation, and Visualization of Magnetosome Gene Clusters.}, journal = {Microbiology resource announcements}, volume = {11}, number = {1}, pages = {e0103121}, pmid = {35023778}, issn = {2576-098X}, support = {41822704//National Natural Science Foundation of China (NSFC)/ ; 41621004//National Natural Science Foundation of China (NSFC)/ ; //Youth Innovation Promotion Association of the Chinese Academy of Sciences (CAS YIPA)/ ; }, abstract = {Magnetosome gene clusters (MGCs), which are responsible for magnetosome biosynthesis and organization in magnetotactic bacteria (MTB), are the key to deciphering the mechanisms and evolutionary origin of magnetoreception, organelle biogenesis, and intracellular biomineralization in bacteria. Here, we report the development of MagCluster, a Python stand-alone tool for efficient exploration of MGCs from large-scale (meta)genomic data.}, } @article {pmid35018470, year = {2022}, author = {von der Heyde, EL and Hallmann, A}, title = {Molecular and cellular dynamics of early embryonic cell divisions in Volvox carteri.}, journal = {The Plant cell}, volume = {34}, number = {4}, pages = {1326-1353}, pmid = {35018470}, issn = {1532-298X}, mesh = {Animals ; Cell Division/genetics ; *Volvox/genetics ; }, abstract = {Cell division is fundamental to all organisms and the green alga used here exhibits both key animal and plant functions. Specifically, we analyzed the molecular and cellular dynamics of early embryonic divisions of the multicellular green alga Volvox carteri (Chlamydomonadales). Relevant proteins related to mitosis and cytokinesis were identified in silico, the corresponding genes were cloned, fused to yfp, and stably expressed in Volvox, and the tagged proteins were studied by live-cell imaging. We reveal rearrangements of the microtubule cytoskeleton during centrosome separation, spindle formation, establishment of the phycoplast, and generation of previously unknown structures. The centrosomes participate in initiation of spindle formation and determination of spindle orientation. Although the nuclear envelope does not break down during early mitosis, intermixing of cytoplasm and nucleoplasm results in loss of nuclear identity. Finally, we present a model for mitosis in Volvox. Our study reveals enormous dynamics, clarifies spatio-temporal relationships of subcellular structures, and provides insight into the evolution of cell division.}, } @article {pmid35014399, year = {2021}, author = {Klein, S and Distel, LVR and Neuhuber, W}, title = {X-ray Dose-Enhancing Impact of Functionalized Au-Fe3O4 Nanoheterodimers on MCF-7 and A549 Multicellular Tumor Spheroids.}, journal = {ACS applied bio materials}, volume = {4}, number = {4}, pages = {3113-3123}, doi = {10.1021/acsabm.0c01494}, pmid = {35014399}, issn = {2576-6422}, mesh = {Biocompatible Materials/chemistry/*pharmacology ; Cell Survival/drug effects ; Ferric Compounds/chemistry/*pharmacology ; Gold/chemistry/*pharmacology ; Humans ; MCF-7 Cells ; Materials Testing ; Nanoparticles/*chemistry ; Particle Size ; Spheroids, Cellular/*drug effects ; *X-Rays ; }, abstract = {The efficiency of nanoparticle-enhanced radiotherapy was studied by loading MCF-7 and A549 multicellular tumor spheroids (MCTSs) with caffeic acid- and nitrosonium-functionalized Au-Fe3O4 nanoheterodimers (Au-Fe3O4 NHDs). Transmission electron microscope images of MCTS cross-sectional sections visualized the invasion and distribution of the nitrosonium- and caffeic acid-functionalized Au-Fe3O4 NHDs (NO- and CA-NHDs) in the A549 and MCF-7 MCTSs, whereas the iron content of the MCTSs were quantified using the ferrozine assay. The synergistic impact of intracellular NO- and CA-NHDs and X-ray irradiation on the growth dynamics of the A549 and MCF-7 MCTSs was surveyed by monitoring their temporal evolution under a light microscope over a period of 14 days. The emergence of hypoxia during the spheroid growth was followed by detecting the lactate efflux of MCTSs without and with NO- and CA-NHDs. The performance of the NO- and CA-NHDs as X-ray dose-enhancing agents in the A549 and MCF-7 MCTSs was clarified by performing clonogenic cell survival assays and determining the respective dose-modifying factors for X-ray doses of 0, 2, 4, and 6 Gy. The NO- and CA-NHDs were shown to perform as potent X-ray dose-enhancing agents in A549 and MCF-7 MCTSs. Moreover, the CA-NHDs boosted their radio-sensitizing efficacy by inhibiting the lactate efflux as impairing metabolic reprogramming. A synergistic effect on the MCTS destruction was observed for the combination of both NHDs since the surfactants differ in their antitumor effect.}, } @article {pmid35013306, year = {2022}, author = {Sforna, MC and Loron, CC and Demoulin, CF and François, C and Cornet, Y and Lara, YJ and Grolimund, D and Ferreira Sanchez, D and Medjoubi, K and Somogyi, A and Addad, A and Fadel, A and Compère, P and Baudet, D and Brocks, JJ and Javaux, EJ}, title = {Intracellular bound chlorophyll residues identify 1 Gyr-old fossils as eukaryotic algae.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {146}, pmid = {35013306}, issn = {2041-1723}, mesh = {Biological Evolution ; Chlorophyll/*chemistry/history ; Chlorophyta/anatomy & histology/classification/physiology/*ultrastructure ; Coordination Complexes/*chemistry ; Democratic Republic of the Congo ; Ecosystem ; Eukaryotic Cells ; *Fossils ; Geologic Sediments/analysis ; History, Ancient ; Microscopy, Electron, Transmission ; Nickel/chemistry ; Photosynthesis/*physiology ; Phylogeny ; Plant Cells/physiology/ultrastructure ; Tetrapyrroles/chemistry ; X-Ray Absorption Spectroscopy ; }, abstract = {The acquisition of photosynthesis is a fundamental step in the evolution of eukaryotes. However, few phototrophic organisms are unambiguously recognized in the Precambrian record. The in situ detection of metabolic byproducts in individual microfossils is the key for the direct identification of their metabolisms. Here, we report a new integrative methodology using synchrotron-based X-ray fluorescence and absorption. We evidence bound nickel-geoporphyrins moieties in low-grade metamorphic rocks, preserved in situ within cells of a ~1 Gyr-old multicellular eukaryote, Arctacellularia tetragonala. We identify these moieties as chlorophyll derivatives, indicating that A. tetragonala was a phototrophic eukaryote, one of the first unambiguous algae. This new approach, applicable to overmature rocks, creates a strong new proxy to understand the evolution of phototrophy and diversification of early ecosystems.}, } @article {pmid35012580, year = {2022}, author = {Kozlov, AP}, title = {Mammalian tumor-like organs. 1. The role of tumor-like normal organs and atypical tumor organs in the evolution of development (carcino-evo-devo).}, journal = {Infectious agents and cancer}, volume = {17}, number = {1}, pages = {2}, pmid = {35012580}, issn = {1750-9378}, support = {Academic Excellence Project 5-100//peter the great st. petersburg polytechnic university/ ; }, abstract = {BACKGROUND: Earlier I hypothesized that hereditary tumors might participate in the evolution of multicellular organisms. I formulated the hypothesis of evolution by tumor neofunctionalization, which suggested that the evolutionary role of hereditary tumors might consist in supplying evolving multicellular organisms with extra cell masses for the expression of evolutionarily novel genes and the origin of new cell types, tissues, and organs. A new theory-the carcino-evo-devo theory-has been developed based on this hypothesis.

MAIN TEXT: My lab has confirmed several non-trivial predictions of this theory. Another non-trivial prediction is that evolutionarily new organs if they originated from hereditary tumors or tumor-like structures, should recapitulate some tumor features in their development. This paper reviews the tumor-like features of evolutionarily novel organs. It turns out that evolutionarily new organs such as the eutherian placenta, mammary gland, prostate, the infantile human brain, and hoods of goldfishes indeed have many features of tumors. I suggested calling normal organs, which have many tumor features, the tumor-like organs.

CONCLUSION: Tumor-like organs might originate from hereditary atypical tumor organs and represent the part of carcino-evo-devo relationships, i.e., coevolution of normal and neoplastic development. During subsequent evolution, tumor-like organs may lose the features of tumors and the high incidence of cancer and become normal organs without (or with almost no) tumor features.}, } @article {pmid37073225, year = {2022}, author = {Chen, H and Li, DH and Jiang, AJ and Li, XG and Wu, SJ and Chen, JW and Qu, MJ and Qi, XQ and Dai, J and Zhao, R and Zhang, WJ and Liu, SS and Wu, LF}, title = {Metagenomic analysis reveals wide distribution of phototrophic bacteria in hydrothermal vents on the ultraslow-spreading Southwest Indian Ridge.}, journal = {Marine life science & technology}, volume = {4}, number = {2}, pages = {255-267}, pmid = {37073225}, issn = {2662-1746}, abstract = {UNLABELLED: Deep-sea hydrothermal vents are known as chemosynthetic ecosystems. However, high temperature vents emit light that hypothetically can drive photosynthesis in this habitat. Metagenomic studies have sporadically reported the occurrence of phototrophic populations such as cyanobacteria in hydrothermal vents. To determine how geographically and taxonomically widespread phototrophs are in deep-sea hydrothermal vents, we collected samples from three niches in a hydrothermal vent on the Southwest Indian Ridge and carried out an integrated metagenomic analysis. We determined the typical community structures of microorganisms found in active venting fields and identified populations of known potential chlorophototrophs and retinalophototrophs. Complete chlorophyll biosynthetic pathways were identified in all samples. By contrast, proteorhodopsins were only found in active beehive smoker diffusers. Taxonomic groups possessing potential phototrophy dependent on semiconductors present in hydrothermal vents were also found in these samples. This systematic comparative metagenomic study reveals the widespread distribution of phototrophic bacteria in hydrothermal vent fields. Our results support the hypothesis that the ocean is a seed bank of diverse microorganisms. Geothermal vent light may provide energy and confer a competitive advantage on phototrophs to proliferate in hydrothermal vent ecosystems.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42995-021-00121-y.}, } @article {pmid34999783, year = {2022}, author = {Leger, MM and Ros-Rocher, N and Najle, SR and Ruiz-Trillo, I}, title = {Rel/NF-κB Transcription Factors Emerged at the Onset of Opisthokonts.}, journal = {Genome biology and evolution}, volume = {14}, number = {1}, pages = {}, pmid = {34999783}, issn = {1759-6653}, mesh = {Animals ; *Eukaryota/metabolism ; *Evolution, Molecular ; *NF-kappa B/genetics/metabolism ; Transcription Factor RelA/genetics/metabolism ; Transcription Factor RelB/genetics/metabolism ; }, abstract = {The Rel/NF-κB transcription factor family has myriad roles in immunity, development, and differentiation in animals, and was considered a key innovation for animal multicellularity. Rel homology domain-containing proteins were previously hypothesized to have originated in a last common ancestor of animals and some of their closest unicellular relatives. However, key taxa were missing from previous analyses, necessitating a systematic investigation into the distribution and evolution of these proteins. Here, we address this knowledge gap by surveying taxonomically broad data from eukaryotes, with a special emphasis on lineages closely related to animals. We report an earlier origin for Rel/NF-κB proteins than previously described, in the last common ancestor of animals and fungi, and show that even in the sister group to fungi, these proteins contain elements that in animals are necessary for the subcellular regulation of Rel/NF-κB.}, } @article {pmid34998872, year = {2022}, author = {Kulkarni, P and Behal, A and Mohanty, A and Salgia, R and Nedelcu, AM and Uversky, VN}, title = {Co-opting disorder into order: Intrinsically disordered proteins and the early evolution of complex multicellularity.}, journal = {International journal of biological macromolecules}, volume = {201}, number = {}, pages = {29-36}, doi = {10.1016/j.ijbiomac.2021.12.182}, pmid = {34998872}, issn = {1879-0003}, mesh = {*Intrinsically Disordered Proteins ; *Volvox ; }, abstract = {Intrinsically disordered proteins (IDPs) are proteins that lack rigid structures yet play important roles in myriad biological phenomena. A distinguishing feature of IDPs is that they often mediate specific biological outcomes via multivalent weak cooperative interactions with multiple partners. Here, we show that several proteins specifically associated with processes that were key in the evolution of complex multicellularity in the lineage leading to the multicellular green alga Volvox carteri are IDPs. We suggest that, by rewiring cellular protein interaction networks, IDPs facilitated the co-option of ancestral pathways for specialized multicellular functions, underscoring the importance of IDPs in the early evolution of complex multicellularity.}, } @article {pmid34992624, year = {2021}, author = {Hemleben, V and Grierson, D and Borisjuk, N and Volkov, RA and Kovarik, A}, title = {Personal Perspectives on Plant Ribosomal RNA Genes Research: From Precursor-rRNA to Molecular Evolution.}, journal = {Frontiers in plant science}, volume = {12}, number = {}, pages = {797348}, pmid = {34992624}, issn = {1664-462X}, abstract = {The history of rDNA research started almost 90 years ago when the geneticist, Barbara McClintock observed that in interphase nuclei of maize the nucleolus was formed in association with a specific region normally located near the end of a chromosome, which she called the nucleolar organizer region (NOR). Cytologists in the twentieth century recognized the nucleolus as a common structure in all eukaryotic cells, using both light and electron microscopy and biochemical and genetic studies identified ribosomes as the subcellular sites of protein synthesis. In the mid- to late 1960s, the synthesis of nuclear-encoded rRNA was the only system in multicellular organisms where transcripts of known function could be isolated, and their synthesis and processing could be studied. Cytogenetic observations of NOR regions with altered structure in plant interspecific hybrids and detailed knowledge of structure and function of rDNA were prerequisites for studies of nucleolar dominance, epistatic interactions of rDNA loci, and epigenetic silencing. In this article, we focus on the early rDNA research in plants, performed mainly at the dawn of molecular biology in the 60 to 80-ties of the last century which presented a prequel to the modern genomic era. We discuss - from a personal view - the topics such as synthesis of rRNA precursor (35S pre-rRNA in plants), processing, and the organization of 35S and 5S rDNA. Cloning and sequencing led to the observation that the transcribed and processed regions of the rRNA genes vary enormously, even between populations and species, in comparison with the more conserved regions coding for the mature rRNAs. Epigenetic phenomena and the impact of hybridization and allopolyploidy on rDNA expression and homogenization are discussed. This historical view of scientific progress and achievements sets the scene for the other articles highlighting the immense progress in rDNA research published in this special issue of Frontiers in Plant Science on "Molecular organization, evolution, and function of ribosomal DNA."}, } @article {pmid34949534, year = {2022}, author = {Graham, AL and Schrom, EC and Metcalf, CJE}, title = {The evolution of powerful yet perilous immune systems.}, journal = {Trends in immunology}, volume = {43}, number = {2}, pages = {117-131}, pmid = {34949534}, issn = {1471-4981}, mesh = {Adaptation, Physiological ; Animals ; Biological Evolution ; *COVID-19 ; Cytokines/genetics ; Humans ; Immune System ; SARS-CoV-2 ; }, abstract = {The mammalian immune system packs serious punch against infection but can also cause harm: for example, coronavirus disease 2019 (COVID-19) made headline news of the simultaneous power and peril of human immune responses. In principle, natural selection leads to exquisite adaptation and therefore cytokine responsiveness that optimally balances the benefits of defense against its costs (e.g., immunopathology suffered and resources expended). Here, we illustrate how evolutionary biology can predict such optima and also help to explain when/why individuals exhibit apparently maladaptive immunopathological responses. Ultimately, we argue that the evolutionary legacies of multicellularity and life-history strategy, in addition to our coevolution with symbionts and our demographic history, together explain human susceptibility to overzealous, pathology-inducing cytokine responses. Evolutionary insight thereby complements molecular/cellular mechanistic insights into immunopathology.}, } @article {pmid34944066, year = {2021}, author = {Yeh, CY and Huang, WH and Chen, HC and Meir, YJ}, title = {Capturing Pluripotency and Beyond.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34944066}, issn = {2073-4409}, mesh = {Animals ; Blastocyst/metabolism ; Cell Differentiation/*genetics ; Cell Lineage/genetics ; Embryonic Development/*genetics ; Embryonic Stem Cells/cytology ; Gene Expression Regulation, Developmental/genetics ; Germ Layers/*growth & development ; Humans ; Mice ; Pluripotent Stem Cells/*cytology ; }, abstract = {During the development of a multicellular organism, the specification of different cell lineages originates in a small group of pluripotent cells, the epiblasts, formed in the preimplantation embryo. The pluripotent epiblast is protected from premature differentiation until exposure to inductive cues in strictly controlled spatially and temporally organized patterns guiding fetus formation. Epiblasts cultured in vitro are embryonic stem cells (ESCs), which recapitulate the self-renewal and lineage specification properties of their endogenous counterparts. The characteristics of totipotency, although less understood than pluripotency, are becoming clearer. Recent studies have shown that a minor ESC subpopulation exhibits expanded developmental potential beyond pluripotency, displaying a characteristic reminiscent of two-cell embryo blastomeres (2CLCs). In addition, reprogramming both mouse and human ESCs in defined media can produce expanded/extended pluripotent stem cells (EPSCs) similar to but different from 2CLCs. Further, the molecular roadmaps driving the transition of various potency states have been clarified. These recent key findings will allow us to understand eutherian mammalian development by comparing the underlying differences between potency network components during development. Using the mouse as a paradigm and recent progress in human PSCs, we review the epiblast's identity acquisition during embryogenesis and their ESC counterparts regarding their pluripotent fates and beyond.}, } @article {pmid34940504, year = {2021}, author = {Folkendt, L and Lohmann, I and Domsch, K}, title = {An Evolutionary Perspective on Hox Binding Site Preferences in Two Different Tissues.}, journal = {Journal of developmental biology}, volume = {9}, number = {4}, pages = {}, pmid = {34940504}, issn = {2221-3759}, abstract = {Transcription factor (TF) networks define the precise development of multicellular organisms. While many studies focused on TFs expressed in specific cell types to elucidate their contribution to cell specification and differentiation, it is less understood how broadly expressed TFs perform their precise functions in the different cellular contexts. To uncover differences that could explain tissue-specific functions of such TFs, we analyzed here genomic chromatin interactions of the broadly expressed Drosophila Hox TF Ultrabithorax (Ubx) in the mesodermal and neuronal tissues using bioinformatics. Our investigations showed that Ubx preferentially interacts with multiple yet tissue-specific chromatin sites in putative regulatory regions of genes in both tissues. Importantly, we found the classical Hox/Ubx DNA binding motif to be enriched only among the neuronal Ubx chromatin interactions, whereas a novel Ubx-like motif with rather low predicted Hox affinities was identified among the regions bound by Ubx in the mesoderm. Finally, our analysis revealed that tissues-specific Ubx chromatin sites are also different with regards to the distribution of active and repressive histone marks. Based on our data, we propose that the tissue-related differences in Ubx binding behavior could be a result of the emergence of the mesoderm as a new germ layer in triploblastic animals, which might have required the Hox TFs to relax their binding specificity.}, } @article {pmid34937533, year = {2021}, author = {Shilovsky, GA and Putyatina, TS and Markov, AV}, title = {Altruism and Phenoptosis as Programs Supported by Evolution.}, journal = {Biochemistry. Biokhimiia}, volume = {86}, number = {12}, pages = {1540-1552}, pmid = {34937533}, issn = {1608-3040}, mesh = {*Altruism ; Animals ; *Apoptosis ; *Biological Evolution ; *COVID-19 ; Humans ; Insecta/physiology ; *SARS-CoV-2 ; }, abstract = {Phenoptosis is a programmed death that has emerged in the process of evolution, sometimes taking the form of an altruistic program. In particular, it is believed to be a weapon against the spread of pandemics in the past and an obstacle in fighting pandemics in the present (COVID). However, on the evolutionary scale, deterministic death is not associated with random relationships (for example, bacteria with a particular mutation), but is a product of higher nervous activity or a consequence of established hierarchy that reaches its maximal expression in eusocial communities of Hymenoptera and highly social communities of mammals. Unlike a simple association of individuals, eusociality is characterized by the appearance of non-reproductive individuals as the highest form of altruism. In contrast to primitive programs for unicellular organisms, higher multicellular organisms are characterized by the development of behavior-based phenoptotic programs, especially in the case of reproduction-associated limitation of lifespan. Therefore, we can say that the development of altruism in the course of evolution of sociality leads in its extreme manifestation to phenoptosis. Development of mathematical models for the emergence of altruism and programmed death contributes to our understanding of mechanisms underlying these paradoxical counterproductive (harmful) programs. In theory, this model can be applied not only to insects, but also to other social animals and even to the human society. Adaptive death is an extreme form of altruism. We consider altruism and programmed death as programmed processes in the mechanistic and adaptive sense, respectively. Mechanistically, this is a program existing as a predetermined chain of certain responses, regardless of its adaptive value. As to its adaptive value (regardless of the degree of "phenoptoticity"), this is a characteristic of organisms that demonstrate high levels of kinship, social organization, and physical association typical for higher-order individuals, e.g., unicellular organisms forming colonies with some characteristics of multicellular animals or colonies of multicellular animals displaying features of supraorganisms.}, } @article {pmid34934939, year = {2021}, author = {Sherlock, BE and Chen, J and Mansfield, JC and Green, E and Winlove, CP}, title = {Biophotonic tools for probing extracellular matrix mechanics.}, journal = {Matrix biology plus}, volume = {12}, number = {}, pages = {100093}, pmid = {34934939}, issn = {2590-0285}, abstract = {The complex, hierarchical and heterogeneous biomechanics of the extracellular matrix (ECM) are central to the health of multicellular organisms. Characterising the distribution, dynamics and above all else origins of ECM biomechanics are challenges that have captivated researchers for decades. Recently, a suite of biophotonics techniques have emerged as powerful new tools to investigate ECM biomechanics. In this mini-review, we discuss how the non-destructive, sub-micron resolution imaging capabilities of Raman spectroscopy and nonlinear microscopy are being used to interrogate the biomechanics of thick, living tissues. These high speed, label-free techniques are implemented during mechanical testing, providing unprecedented insight into the compositional and structural response of the ECM to changes in the mechanical environment.}, } @article {pmid34932575, year = {2021}, author = {Maltseva, AL and Varfolomeeva, MA and Gafarova, ER and Panova, MAZ and Mikhailova, NA and Granovitch, AI}, title = {Divergence together with microbes: A comparative study of the associated microbiomes in the closely related Littorina species.}, journal = {PloS one}, volume = {16}, number = {12}, pages = {e0260792}, pmid = {34932575}, issn = {1932-6203}, mesh = {Animals ; Bacteria/classification/genetics/*isolation & purification ; Environmental Microbiology ; *Genetic Variation ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Snails/classification/*microbiology ; Species Specificity ; }, abstract = {Any multicellular organism during its life is involved in relatively stable interactions with microorganisms. The organism and its microbiome make up a holobiont, possessing a unique set of characteristics and evolving as a whole system. This study aimed to evaluate the degree of the conservativeness of microbiomes associated with intertidal gastropods. We studied the composition and the geographic and phylogenetic variability of the gut and body surface microbiomes of five closely related sympatric Littorina (Neritrema) spp. and a more distant species, L. littorea, from the sister subgenus Littorina (Littorina). Although snail-associated microbiomes included many lineages (207-603), they were dominated by a small number of OTUs of the genera Psychromonas, Vibrio, and Psychrilyobacter. The geographic variability was greater than the interspecific differences at the same collection site. While the microbiomes of the six Littorina spp. did not differ at the high taxonomic level, the OTU composition differed between groups of cryptic species and subgenera. A few species-specific OTUs were detected within the collection sites; notably, such OTUs never dominated microbiomes. We conclude that the composition of the high-rank taxa of the associated microbiome ("scaffolding enterotype") is more evolutionarily conserved than the composition of the low-rank individual OTUs, which may be site- and / or species-specific.}, } @article {pmid34913456, year = {2022}, author = {Gurney, J and Simonet, C and Wollein Waldetoft, K and Brown, SP}, title = {Challenges and opportunities for cheat therapy in the control of bacterial infections.}, journal = {Natural product reports}, volume = {39}, number = {2}, pages = {325-334}, doi = {10.1039/d1np00053e}, pmid = {34913456}, issn = {1460-4752}, mesh = {*Bacterial Infections/drug therapy ; *Biological Evolution ; Humans ; }, abstract = {Covering: 1999 to 2021Bacterial pathogens can be highly social, communicating and cooperating within multi-cellular groups to make us sick. The requirement for collective action in pathogens presents novel therapeutic avenues that seek to undermine cooperative behavior, what we call here 'cheat therapies'. We review two broad avenues of cheat therapy: first, the introduction of genetically engineered 'cheat' strains (bio-control cheats), and second the chemical induction of 'cheat' behavior in the infecting pathogens (chemical-control cheats). Both genetically engineered and chemically induced cheats can socially exploit the cooperative wildtype infection, reducing pathogen burden and the severity of disease. We review the costs and benefits of cheat therapies, highlighting advantages of evolutionary robustness and also the challenges of low to moderate efficacy, compared to conventional antibiotic treatments. We end with a summary of what we see as the most valuable next steps, focusing on adjuvant treatments and use as alternate therapies for mild, self-resolving infections - allowing the reservation of current and highly effective antibiotics for more critical patient needs.}, } @article {pmid34890552, year = {2021}, author = {Brückner, A and Badroos, JM and Learsch, RW and Yousefelahiyeh, M and Kitchen, SA and Parker, J}, title = {Evolutionary assembly of cooperating cell types in an animal chemical defense system.}, journal = {Cell}, volume = {184}, number = {25}, pages = {6138-6156.e28}, doi = {10.1016/j.cell.2021.11.014}, pmid = {34890552}, issn = {1097-4172}, mesh = {Animals ; Benzoquinones/*metabolism ; Biological Evolution ; Biosynthetic Pathways ; Coleoptera/*metabolism ; Drosophila melanogaster/*metabolism ; Pheromones/*metabolism ; }, abstract = {How the functions of multicellular organs emerge from the underlying evolution of cell types is poorly understood. We deconstructed evolution of an organ novelty: a rove beetle gland that secretes a defensive cocktail. We show how gland function arose via assembly of two cell types that manufacture distinct compounds. One cell type, comprising a chemical reservoir within the abdomen, produces alkane and ester compounds. We demonstrate that this cell type is a hybrid of cuticle cells and ancient pheromone and adipocyte-like cells, executing its function via a mosaic of enzymes from each parental cell type. The second cell type synthesizes benzoquinones using a chimera of conserved cellular energy and cuticle formation pathways. We show that evolution of each cell type was shaped by coevolution between the two cell types, yielding a potent secretion that confers adaptive value. Our findings illustrate how cooperation between cell types arises, generating new, organ-level behaviors.}, } @article {pmid34884742, year = {2021}, author = {Troitskaya, O and Novak, D and Nushtaeva, A and Savinkova, M and Varlamov, M and Ermakov, M and Richter, V and Koval, O}, title = {EGFR Transgene Stimulates Spontaneous Formation of MCF7 Breast Cancer Cells Spheroids with Partly Loss of HER3 Receptor.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884742}, issn = {1422-0067}, support = {20-74-10039//Russian Science Foundation/ ; 121030200173-6//Russian State Funded Budget Project/ ; }, mesh = {CD24 Antigen/metabolism ; Cell Culture Techniques, Three Dimensional ; *Genes, erbB-1 ; Humans ; Hyaluronan Receptors/metabolism ; *MCF-7 Cells ; Receptor, ErbB-3/*metabolism ; Rhodamine 123 ; *Spheroids, Cellular ; Transgenes ; Tumor Cells, Cultured ; }, abstract = {Multicellular spheroids with 3D cell-cell interactions are a useful model to simulate the growth conditions of cancer. There is evidence that in tumor spheroids, the expression of various essential molecules is changed compared to the adherent form of cell cultures. These changes include growth factor receptors and ABC transporters and result in the enhanced invasiveness of the cells and drug resistance. It is known that breast adenocarcinoma MCF7 cells can spontaneously form 3D spheroids and such spheroids are characterized by high expression of EGFR/HER2, while the natural phenotype of MCF7 cells is EGFR[low]/HER2[low]. Therefore, it was interesting to reveal if high epidermal growth factor receptor (EGFR) expression is sufficient for the conversion of adherent MCF7 to spheroids. In this study, an MCF7 cell line with high expression of EGFR was engineered using the retroviral transduction method. These MCF7-EGFR cells assembled in spheroids very quickly and grew predominantly as a 3D suspension culture with no special plates, scaffolds, growth supplements, or exogenous matrixes. These spheroids were characterized by a rounded shape with a well-defined external border and 100 µM median diameter. The sphere-forming ability of MCF7-EGFR cells was up to 5 times stronger than in MCF7[wt] cells. Thus, high EGFR expression was the initiation factor of conversion of adherent MCF7[wt] cells to spheroids. MCF7-EGFR spheroids were enriched by the cells with a cancer stem cell (CSC) phenotype CD24[-/low]/CD44[-] in comparison with parental MCF7[wt] cells and MCF7-EGFR adhesive cells. We suppose that these properties of MCF7-EGFR spheroids originate from the typical features of parental MCF7 cells. We showed the decreasing of HER3 receptors in MCF7-EGFR spheroids compared to that in MCF[wt] and in adherent MCF7-EGFR cells, and the same decrease was observed in the MCF7[wt] spheroids growing under the growth factors stimulation. To summarize, the expression of EGFR transgene in MCF7 cells stimulates rapid spheroids formation; these spheroids are enriched by CSC-like CD24[-]/CD44[-] cells, they partly lose HER3 receptors, and are characterized by a lower potency in drug resistance pomp activation compared to MCF7[wt]. These MCF7-EGFR spheroids are a useful cancer model for the development of anticancer drugs, including EGFR-targeted therapeutics.}, } @article {pmid34878516, year = {2022}, author = {Suissa, JS}, title = {Fern fronds that move like pine cones: humidity-driven motion of fertile leaflets governs the timing of spore dispersal in a widespread fern species.}, journal = {Annals of botany}, volume = {129}, number = {5}, pages = {519-528}, pmid = {34878516}, issn = {1095-8290}, mesh = {*Ferns/physiology ; Germ Cells, Plant ; Humidity ; Plant Cone ; Spores/physiology ; Spores, Fungal ; }, abstract = {BACKGROUND AND AIMS: The sensitive fern, Onoclea sensibilis, is a widespread species in eastern North America and has an atypical timing of spore dispersal among temperate ferns. During early summer, this dimorphic species produces heavily modified spore-bearing fronds with leaflets tightly enveloping their sporangia and spores. These fronds senesce and persist above ground as dead mature structures until the following early spring when the leaflets finally open and spores are dispersed. While this timing of spore dispersal has been observed for over 120 years, the structural mechanisms underpinning this phenology have remained elusive.

METHODS: Based on field observations, growth chamber manipulations and scanning electron microscopy, the mechanisms underlying this distinctive timing of spore dispersal in the sensitive fern were investigated.

KEY RESULTS: I show that fertile leaflets of the sensitive fern move in direct response to changes in humidity, exhibiting structural and functional parallels with multicellular hygromorphic structures in seed plants, such as pine cones. These parallels include differences in cellulose microfibril orientation in cells on the abaxial and adaxial sides of the leaflet. The dynamics of this hygroscopic movement concomitant with regular abscission zones along the pinnules and coordinated senescence lead to the specific timing of early spring spore dispersal in the sensitive fern.

CONCLUSIONS: While hygroscopic movement is common in seed-free plants, it mostly occurs in small structures that are either one or a few cells in size, such as the leptosporangium. Given its multicellular structure and integration across many cells and tissues, the movement and construction of the sensitive fern pinnules are more similar to structures in seed plants. The evolution of this complex trait in the sensitive fern efficiently regulates the timing of spore release, leading to early spring dispersal. This phenology likely gives gametophytes and subsequent sporophytes an advantage with early germination and growth.}, } @article {pmid34873026, year = {2021}, author = {Wade, J and Byrne, DJ and Ballentine, CJ and Drakesmith, H}, title = {Temporal variation of planetary iron as a driver of evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {51}, pages = {}, pmid = {34873026}, issn = {1091-6490}, support = {MC_UU_00008/10/MRC_/Medical Research Council/United Kingdom ; MC_UU_12010/10/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Biological Availability ; *Biological Evolution ; Earth, Planet ; Ecosystem ; *Evolution, Planetary ; Genetic Variation ; Geology ; Host-Pathogen Interactions ; Iron/chemistry/*metabolism ; Oxidation-Reduction ; Siderophores/metabolism ; Water/chemistry/metabolism ; }, abstract = {Iron is an irreplaceable component of proteins and enzyme systems required for life. This need for iron is a well-characterized evolutionary mechanism for genetic selection. However, there is limited consideration of how iron bioavailability, initially determined by planetary accretion but fluctuating considerably at global scale over geological time frames, has shaped the biosphere. We describe influences of iron on planetary habitability from formation events >4 Gya and initiation of biochemistry from geochemistry through oxygenation of the atmosphere to current host-pathogen dynamics. By determining the iron and transition element distribution within the terrestrial planets, planetary core formation is a constraint on both the crustal composition and the longevity of surface water, hence a planet's habitability. As such, stellar compositions, combined with metallic core-mass fraction, may be an observable characteristic of exoplanets that relates to their ability to support life. On Earth, the stepwise rise of atmospheric oxygen effectively removed gigatons of soluble ferrous iron from habitats, generating evolutionary pressures. Phagocytic, infectious, and symbiotic behaviors, dating from around the Great Oxygenation Event, refocused iron acquisition onto biotic sources, while eukaryotic multicellularity allows iron recycling within an organism. These developments allow life to more efficiently utilize a scarce but vital nutrient. Initiation of terrestrial life benefitted from the biochemical properties of abundant mantle/crustal iron, but the subsequent loss of iron bioavailability may have been an equally important driver of compensatory diversity. This latter concept may have relevance for the predicted future increase in iron deficiency across the food chain caused by elevated atmospheric CO2.}, } @article {pmid34870903, year = {2021}, author = {Prostak, SM and Fritz-Laylin, LK}, title = {Laboratory Maintenance of the Chytrid Fungus Batrachochytrium dendrobatidis.}, journal = {Current protocols}, volume = {1}, number = {12}, pages = {e309}, doi = {10.1002/cpz1.309}, pmid = {34870903}, issn = {2691-1299}, support = {//National Science Foundation/ ; }, mesh = {Amphibians ; Animals ; Batrachochytrium ; *Chytridiomycota ; Ecosystem ; Laboratories ; }, abstract = {The chytrid fungus Batrachochytrium dendrobatidis (Bd) is a causative agent of chytridiomycosis, a skin disease associated with amphibian population declines around the world. Despite the major impact Bd is having on global ecosystems, much of Bd's basic biology remains unstudied. In addition to revealing mechanisms driving the spread of chytridiomycosis, studying Bd can shed light on the evolution of key fungal traits because chytrid fungi, including Bd, diverged before the radiation of the Dikaryotic fungi (multicellular fungi and yeast). Studying Bd in the laboratory is, therefore, of growing interest to a wide range of scientists, ranging from herpetologists and disease ecologists to molecular, cell, and evolutionary biologists. This protocol describes how to maintain developmentally synchronized liquid cultures of Bd for use in the laboratory, how to grow Bd on solid media, as well as cryopreservation and revival of frozen stocks. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Reviving cryopreserved Bd cultures Basic Protocol 2: Establishing synchronized liquid cultures of Bd Basic Protocol 3: Regular maintenance of synchronous Bd in liquid culture Alternate Protocol 1: Regular maintenance of asynchronous Bd in liquid culture Basic Protocol 4: Regular maintenance of synchronous Bd on solid medium Alternate Protocol 2: Starting a culture on solid medium from a liquid culture Basic Protocol 5: Cryopreservation of Bd.}, } @article {pmid34857936, year = {2021}, author = {Liu, K and Deng, S and Ye, C and Yao, Z and Wang, J and Gong, H and Liu, L and He, X}, title = {Mapping single-cell-resolution cell phylogeny reveals cell population dynamics during organ development.}, journal = {Nature methods}, volume = {18}, number = {12}, pages = {1506-1514}, pmid = {34857936}, issn = {1548-7105}, mesh = {Alleles ; Animals ; Animals, Genetically Modified ; Cell Division ; Cell Lineage ; Computational Biology/*methods ; DNA Replication ; Drosophila melanogaster/embryology/*metabolism ; Endonucleases/metabolism ; Likelihood Functions ; Male ; Microscopy/*methods ; Mutagenesis ; *Mutation ; Phenotype ; Phylogeny ; Saccharomyces cerevisiae/genetics ; Single-Cell Analysis ; }, abstract = {Mapping the cell phylogeny of a complex multicellular organism relies on somatic mutations accumulated from zygote to adult. Available cell barcoding methods can record about three mutations per barcode, enabling only low-resolution mapping of the cell phylogeny of complex organisms. Here we developed SMALT, a substitution mutation-aided lineage-tracing system that outperforms the available cell barcoding methods in mapping cell phylogeny. We applied SMALT to Drosophila melanogaster and obtained on average more than 20 mutations on a three-kilobase-pair barcoding sequence in early-adult cells. Using the barcoding mutations, we obtained high-quality cell phylogenetic trees, each comprising several thousand internal nodes with 84-93% median bootstrap support. The obtained cell phylogenies enabled a population genetic analysis that estimates the longitudinal dynamics of the number of actively dividing parental cells (Np) in each organ through development. The Np dynamics revealed the trajectory of cell births and provided insight into the balance of symmetric and asymmetric cell division.}, } @article {pmid34853303, year = {2021}, author = {Pennemann, FL and Mussabekova, A and Urban, C and Stukalov, A and Andersen, LL and Grass, V and Lavacca, TM and Holze, C and Oubraham, L and Benamrouche, Y and Girardi, E and Boulos, RE and Hartmann, R and Superti-Furga, G and Habjan, M and Imler, JL and Meignin, C and Pichlmair, A}, title = {Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {7009}, pmid = {34853303}, issn = {2041-1723}, mesh = {Animals ; Antiviral Agents ; Drosophila melanogaster ; Evolution, Molecular ; Humans ; *Immunity, Innate ; Mice ; Nucleic Acids/*chemistry/*immunology ; Protein Serine-Threonine Kinases ; Proteomics ; RNA Interference ; RNA, Double-Stranded ; Species Specificity ; THP-1 Cells ; Viral Proteins/*chemistry/*immunology ; }, abstract = {The cell intrinsic antiviral response of multicellular organisms developed over millions of years and critically relies on the ability to sense and eliminate viral nucleic acids. Here we use an affinity proteomics approach in evolutionary distant species (human, mouse and fly) to identify proteins that are conserved in their ability to associate with diverse viral nucleic acids. This approach shows a core of orthologous proteins targeting viral genetic material and species-specific interactions. Functional characterization of the influence of 181 candidates on replication of 6 distinct viruses in human cells and flies identifies 128 nucleic acid binding proteins with an impact on virus growth. We identify the family of TAO kinases (TAOK1, -2 and -3) as dsRNA-interacting antiviral proteins and show their requirement for type-I interferon induction. Depletion of TAO kinases in mammals or flies leads to an impaired response to virus infection characterized by a reduced induction of interferon stimulated genes in mammals and impaired expression of srg1 and diedel in flies. Overall, our study shows a larger set of proteins able to mediate the interaction between viral genetic material and host factors than anticipated so far, attesting to the ancestral roots of innate immunity and to the lineage-specific pressures exerted by viruses.}, } @article {pmid34849893, year = {2022}, author = {Takeuchi, N and Mitarai, N and Kaneko, K}, title = {A scaling law of multilevel evolution: how the balance between within- and among-collective evolution is determined.}, journal = {Genetics}, volume = {220}, number = {2}, pages = {}, pmid = {34849893}, issn = {1943-2631}, mesh = {*Altruism ; *Biological Evolution ; Computer Simulation ; Genetics, Population ; Phenotype ; Selection, Genetic ; }, abstract = {Numerous living systems are hierarchically organized, whereby replicating components are grouped into reproducing collectives-e.g., organelles are grouped into cells, and cells are grouped into multicellular organisms. In such systems, evolution can operate at two levels: evolution among collectives, which tends to promote selfless cooperation among components within collectives (called altruism), and evolution within collectives, which tends to promote cheating among components within collectives. The balance between within- and among-collective evolution thus exerts profound impacts on the fitness of these systems. Here, we investigate how this balance depends on the size of a collective (denoted by N) and the mutation rate of components (m) through mathematical analyses and computer simulations of multiple population genetics models. We first confirm a previous result that increasing N or m accelerates within-collective evolution relative to among-collective evolution, thus promoting the evolution of cheating. Moreover, we show that when within- and among-collective evolution exactly balance each other out, the following scaling relation generally holds: Nmα is a constant, where scaling exponent α depends on multiple parameters, such as the strength of selection and whether altruism is a binary or quantitative trait. This relation indicates that although N and m have quantitatively distinct impacts on the balance between within- and among-collective evolution, their impacts become identical if m is scaled with a proper exponent. Our results thus provide a novel insight into conditions under which cheating or altruism evolves in hierarchically organized replicating systems.}, } @article {pmid34849891, year = {2021}, author = {Varahan, S and Laxman, S}, title = {Bend or break: how biochemically versatile molecules enable metabolic division of labor in clonal microbial communities.}, journal = {Genetics}, volume = {219}, number = {2}, pages = {}, pmid = {34849891}, issn = {1943-2631}, support = {IA/E/16/1/502996/WTDBT_/DBT-Wellcome Trust India Alliance/India ; }, mesh = {Evolution, Molecular ; *Microbial Consortia ; *Microbial Interactions ; Yeasts/genetics/metabolism/physiology ; }, abstract = {In fluctuating nutrient environments, isogenic microbial cells transition into "multicellular" communities composed of phenotypically heterogeneous cells, showing functional specialization. In fungi (such as budding yeast), phenotypic heterogeneity is often described in the context of cells switching between different morphotypes (e.g., yeast to hyphae/pseudohyphae or white/opaque transitions in Candida albicans). However, more fundamental forms of metabolic heterogeneity are seen in clonal Saccharomyces cerevisiae communities growing in nutrient-limited conditions. Cells within such communities exhibit contrasting, specialized metabolic states, and are arranged in distinct, spatially organized groups. In this study, we explain how such an organization can stem from self-organizing biochemical reactions that depend on special metabolites. These metabolites exhibit plasticity in function, wherein the same metabolites are metabolized and utilized for distinct purposes by different cells. This in turn allows cell groups to function as specialized, interdependent cross-feeding systems which support distinct metabolic processes. Exemplifying a system where cells exhibit either gluconeogenic or glycolytic states, we highlight how available metabolites can drive favored biochemical pathways to produce new, limiting resources. These new resources can themselves be consumed or utilized distinctly by cells in different metabolic states. This thereby enables cell groups to sustain contrasting, even apparently impossible metabolic states with stable transcriptional and metabolic signatures for a given environment, and divide labor in order to increase community fitness or survival. We speculate on possible evolutionary implications of such metabolic specialization and division of labor in isogenic microbial communities.}, } @article {pmid34848727, year = {2021}, author = {Benaissa, H and Ounoughi, K and Aujard, I and Fischer, E and Goïame, R and Nguyen, J and Tebo, AG and Li, C and Le Saux, T and Bertolin, G and Tramier, M and Danglot, L and Pietrancosta, N and Morin, X and Jullien, L and Gautier, A}, title = {Engineering of a fluorescent chemogenetic reporter with tunable color for advanced live-cell imaging.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {6989}, pmid = {34848727}, issn = {2041-1723}, mesh = {Animals ; Biocompatible Materials ; Biosensing Techniques ; Color ; Coloring Agents ; Diagnostic Imaging/*methods ; Electronics ; Female ; *Fluorescence ; Fluorescence Resonance Energy Transfer ; Fluorescent Dyes ; Green Fluorescent Proteins ; Male ; Neurons ; Protein Engineering/*methods ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Biocompatible fluorescent reporters with spectral properties spanning the entire visible spectrum are indispensable tools for imaging the biochemistry of living cells and organisms in real time. Here, we report the engineering of a fluorescent chemogenetic reporter with tunable optical and spectral properties. A collection of fluorogenic chromophores with various electronic properties enables to generate bimolecular fluorescent assemblies that cover the visible spectrum from blue to red using a single protein tag engineered and optimized by directed evolution and rational design. The ability to tune the fluorescence color and properties through simple molecular modulation provides a broad experimental versatility for imaging proteins in live cells, including neurons, and in multicellular organisms, and opens avenues for optimizing Förster resonance energy transfer (FRET) biosensors in live cells. The ability to tune the spectral properties and fluorescence performance enables furthermore to match the specifications and requirements of advanced super-resolution imaging techniques.}, } @article {pmid34841798, year = {2021}, author = {Yu, D and Cao, H and Wang, X}, title = {[Advances and applications of organoids: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3961-3974}, doi = {10.13345/j.cjb.200764}, pmid = {34841798}, issn = {1872-2075}, mesh = {*Gene Editing ; Humans ; Models, Biological ; *Organoids ; Regenerative Medicine ; Stem Cells ; }, abstract = {Novel model systems have provided powerful tools for the research of human biology. Despite of being widely used, the conventional research models could not precisely describe the human physiological phenomenon. Organoids are three-dimensional multicellular aggregates derived from stem cells or organ progenitors that could differentiate and self-organize to recapitulate some specific functionalities and architectures of their in vivo counterpart organs. Organoids can be used to simulate organogenesis because of their human origin. In addition, the genomic stability of organoids could be well maintained during long-term amplification in vitro. Moreover, organoids can be cryopreserved as a live biobank for high-throughput screening. Combinatorial use of organoids with other emerging technologies (e.g. gene editing, organ-on-a-chip and single-cell RNA sequencing) could overcome the bottlenecks of conventional models and provide valuable information for disease modelling, pharmaceutical research, precision medicine and regenerative medicine at the organ level. This review summarizes the classifications, characteristics, current applications, combined use with other technologies and future prospects of organoids.}, } @article {pmid34838795, year = {2022}, author = {Tverskoi, D and Gavrilets, S}, title = {The evolution of germ-soma specialization under different genetic and environmental effects.}, journal = {Journal of theoretical biology}, volume = {534}, number = {}, pages = {110964}, doi = {10.1016/j.jtbi.2021.110964}, pmid = {34838795}, issn = {1095-8541}, mesh = {*Biological Evolution ; Cell Differentiation ; Climate ; Fertility ; Humans ; *Models, Biological ; }, abstract = {Division of labor exists at different levels of biological organization - from cell colonies to human societies. One of the simplest examples of the division of labor in multicellular organisms is germ-soma specialization, which plays a key role in the evolution of organismal complexity. Here we formulate and study a general mathematical model exploring the emergence of germ-soma specialization in colonies of cells. We consider a finite population of colonies competing for resources. Colonies are of the same size and are composed by asexually reproducing haploid cells. Each cell can contribute to activity and fecundity of the colony, these contributions are traded-off. We assume that all cells within a colony are genetically identical but gene effects on fecundity and activity are influenced by variation in the microenvironment experienced by individual cells. Through analytical theory and evolutionary agent-based modeling we show that the shape of the trade-off relation between somatic and reproductive functions, the type and extent of variation in within-colony microenvironment, and, in some cases, the number of genes involved, are important predictors of the extent of germ-soma specialization. Specifically, increasing convexity of the trade-off relation, the number of different environmental gradients acting within a colony, and the number of genes (in the case of random microenvironmental effects) promote the emergence of germ-soma specialization. Overall our results contribute towards a better understanding of the role of genetic, environmental, and microenvironmental factors in the evolution of germ-soma specialization.}, } @article {pmid34834691, year = {2021}, author = {Medina, MC and Sousa-Baena, MS and Capelli, NDV and Koch, R and Demarco, D}, title = {Stinging Trichomes in Apocynaceae and Their Evolution in Angiosperms.}, journal = {Plants (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {34834691}, issn = {2223-7747}, support = {#03/12595-7; #04/09729-4//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; }, abstract = {Stinging trichomes are rare in plants, occurring only in angiosperms, where they are reported for a few genera belonging to six families. Although there is no report of stinging trichomes in Apocynaceae, previous fieldwork collections of Fischeria and Matelea caused us a mild allergic reaction on the skin when we contacted the dense indumentum of the plants. This fact associated with the well-known presence of glandular trichomes with acute apex in both genera raised suspicions that stinging trichomes could be present in the family. Hence, this study aimed to investigate the likely occurrence of stinging trichomes in Fischeria and Matelea. We analyzed vegetative shoots and leaves of Fischeria stellata and Matelea denticulata through the usual procedures of light and scanning electron microscopy. We also performed several histochemical tests to investigate the chemical composition of trichome secretion. We detected that glandular trichomes occur throughout the surface of the leaf and stem. They are multicellular, uniseriate with an apical secretory cell, which has a dilated base and a needle-shaped apex. The secretion is compressed into the acuminate portion of the apical cell by a large vacuole, and crystals are deposited in the cell wall in a subapical position, providing a preferential site of rupture. The secretion, composed of amino acids and/or proteins, is released under mechanical action, causing skin irritation. Based on our detailed morphological and anatomical analyses, and in the functional aspects observed, we concluded that the glandular trichomes in Fischeria and Matelea can indeed be classified as stinging. Thus, Apocynaceae is the seventh family for which this type of trichome has been reported. We also compiled information on stinging trichomes in all families of angiosperms. Their phylogenetic distribution indicates that they have evolved at least 12 times during angiosperm evolution and may represent an evolutionary convergence of plant defense against herbivory.}, } @article {pmid34830470, year = {2021}, author = {Kertmen, A and Petrenko, I and Schimpf, C and Rafaja, D and Petrova, O and Sivkov, V and Nekipelov, S and Fursov, A and Stelling, AL and Heimler, K and Rogoll, A and Vogt, C and Ehrlich, H}, title = {Calcite Nanotuned Chitinous Skeletons of Giant Ianthella basta Marine Demosponge.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830470}, issn = {1422-0067}, support = {HE 394/3.//DFG/ ; }, mesh = {Animals ; Aquatic Organisms/*chemistry ; Biomineralization ; Calcium Carbonate/*chemistry ; Chitin/chemistry ; Porifera/*chemistry ; Skeleton/*chemistry ; Spectroscopy, Fourier Transform Infrared ; Tissue Scaffolds/chemistry ; X-Ray Diffraction ; }, abstract = {Marine sponges were among the first multicellular organisms on our planet and have survived to this day thanks to their unique mechanisms of chemical defense and the specific design of their skeletons, which have been optimized over millions of years of evolution to effectively inhabit the aquatic environment. In this work, we carried out studies to elucidate the nature and nanostructural organization of three-dimensional skeletal microfibers of the giant marine demosponge Ianthella basta, the body of which is a micro-reticular, durable structure that determines the ideal filtration function of this organism. For the first time, using the battery of analytical tools including three-dimensional micro-X-ray Fluorescence (3D-µXRF), X-ray diffraction (XRD), infra-red (FTIR), Raman and Near Edge X-ray Fine Structure (NEXAFS) spectroscopy, we have shown that biomineral calcite is responsible for nano-tuning the skeletal fibers of this sponge species. This is the first report on the presence of a calcitic mineral phase in representatives of verongiid sponges which belong to the class Demospongiae. Our experimental data suggest a possible role for structural amino polysaccharide chitin as a template for calcification. Our study suggests further experiments to elucidate both the origin of calcium carbonate inside the skeleton of this sponge and the mechanisms of biomineralization in the surface layers of chitin microfibers saturated with bromotyrosines, which have effective antimicrobial properties and are responsible for the chemical defense of this organism. The discovery of the calcified phase in the chitinous template of I. basta skeleton is expected to broaden the knowledge in biomineralization science where the calcium carbonate is regarded as a valuable material for applications in biomedicine, environmental science, and even in civil engineering.}, } @article {pmid34830263, year = {2021}, author = {Pereira, PHS and Garcia, CRS}, title = {Evidence of G-Protein-Coupled Receptors (GPCR) in the Parasitic Protozoa Plasmodium falciparum-Sensing the Host Environment and Coupling within Its Molecular Signaling Toolkit.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830263}, issn = {1422-0067}, support = {2017/08684-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Animals ; Antimalarials/pharmacology/therapeutic use ; Calcium/metabolism ; Calcium Signaling/drug effects/*physiology ; Host-Parasite Interactions/*physiology ; Humans ; Malaria, Falciparum/drug therapy/*metabolism/parasitology ; Molecular Targeted Therapy/methods ; Perception/drug effects/*physiology ; Plasmodium falciparum/*metabolism ; Protein Binding ; Protozoan Proteins/*metabolism ; Receptors, G-Protein-Coupled/antagonists & inhibitors/*metabolism ; }, abstract = {Throughout evolution, the need for single-celled organisms to associate and form a single cluster of cells has had several evolutionary advantages. In complex, multicellular organisms, each tissue or organ has a specialty and function that make life together possible, and the organism as a whole needs to act in balance and adapt to changes in the environment. Sensory organs are essential for connecting external stimuli into a biological response, through the senses: sight, smell, taste, hearing, and touch. The G-protein-coupled receptors (GPCRs) are responsible for many of these senses and therefore play a key role in the perception of the cells' external environment, enabling interaction and coordinated development between each cell of a multicellular organism. The malaria-causing protozoan parasite, Plasmodium falciparum, has a complex life cycle that is extremely dependent on a finely regulated cellular signaling machinery. In this review, we summarize strong evidence and the main candidates of GPCRs in protozoan parasites. Interestingly, one of these GPCRs is a sensor for K[+] shift in Plasmodium falciparum, PfSR25. Studying this family of proteins in P. falciparum could have a significant impact, both on understanding the history of the evolution of GPCRs and on finding new targets for antimalarials.}, } @article {pmid34825884, year = {2021}, author = {Li, XG and Lin, J and Bai, SJ and Dai, J and Jiao, ZX and Tang, HZ and Qi, XQ and Zhang, WJ and Liu, M and Xu, JS and Wu, LF}, title = {Crassaminicella thermophila sp. nov., a moderately thermophilic bacterium isolated from a deep-sea hydrothermal vent chimney and emended description of the genus Crassaminicella.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {71}, number = {11}, pages = {}, doi = {10.1099/ijsem.0.005112}, pmid = {34825884}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Clostridiaceae/*classification/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Hydrothermal Vents/microbiology ; Indian Ocean ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/microbiology ; Sequence Analysis, DNA ; }, abstract = {A novel moderately thermophilic, anaerobic, heterotrophic bacterium (strain SY095[T]) was isolated from a hydrothermal vent chimney located on the Southwest Indian Ridge at a depth of 2730 m. Cells were Gram-stain-positive, motile, straight to slightly curved rods forming terminal endospores. SY095[T] was grown at 45-60 °C (optimum 50-55 °C), pH 6.0-7.5 (optimum 7.0), and in a salinity of 1-4.5 % (w/v) NaCl (optimum 2.5 %). Substrates utilized by SY095[T] included fructose, glucose, maltose, N-acetyl glucosamine and tryptone. Casamino acid and amino acids (glutamate, glutamine, lysine, methionine, serine and histidine) were also utilized. The main end products from glucose fermentation were acetate, H2 and CO2. Elemental sulphur, sulphate, thiosulphate, sulphite, fumarate, nitrate, nitrite and Fe(III) were not used as terminal electron acceptors. The predominant cellular fatty acids were C14 : 0 (60.5%) and C16 : 0 (7.6 %). The main polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, five unidentified phospholipids and two unidentified aminophospholipids. No respiratory quinones were detected. The chromosomal DNA G+C content was 30.8 mol%. The results of phylogenetic analysis of the 16S rRNA gene sequences indicated that SY095[T] was closely related to Crassaminicella profunda Ra1766H[T] (95.8 % 16S rRNA gene sequence identity). SY095[T] exhibited 78.1 % average nucleotide identity (ANI) to C. profunda Ra1766H[T]. The in silico DNA-DNA hybridization (DDH) value indicated that SY095[T] shared 22.7 % DNA relatedness with C. profunda Ra1766H[T]. On the basis of its phenotypic, genotypic and phylogenetic characteristics, SY095[T] is suggested to represent a novel species of the genus Crassaminicella, for which the name Crassaminicella thermophila sp. nov. is proposed. The type strain is SY095[T] (=JCM 34213=MCCC 1K04191). An emended description of the genus Crassaminicella is also proposed.}, } @article {pmid34814752, year = {2021}, author = {Irisarri, I and Darienko, T and Pröschold, T and Fürst-Jansen, JMR and Jamy, M and de Vries, J}, title = {Unexpected cryptic species among streptophyte algae most distant to land plants.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1963}, pages = {20212168}, pmid = {34814752}, issn = {1471-2954}, mesh = {*Chlorophyta/genetics ; *Embryophyta/genetics ; Evolution, Molecular ; Genome ; Phylogeny ; Plants/genetics ; }, abstract = {Streptophytes are one of the major groups of the green lineage (Chloroplastida or Viridiplantae). During one billion years of evolution, streptophytes have radiated into an astounding diversity of uni- and multicellular green algae as well as land plants. Most divergent from land plants is a clade formed by Mesostigmatophyceae, Spirotaenia spp. and Chlorokybophyceae. All three lineages are species-poor and the Chlorokybophyceae consist of a single described species, Chlorokybus atmophyticus. In this study, we used phylogenomic analyses to shed light into the diversity within Chlorokybus using a sampling of isolates across its known distribution. We uncovered a consistent deep genetic structure within the Chlorokybus isolates, which prompted us to formally extend the Chlorokybophyceae by describing four new species. Gene expression differences among Chlorokybus species suggest certain constitutive variability that might influence their response to environmental factors. Failure to account for this diversity can hamper comparative genomic studies aiming to understand the evolution of stress response across streptophytes. Our data highlight that future studies on the evolution of plant form and function can tap into an unknown diversity at key deep branches of the streptophytes.}, } @article {pmid34814750, year = {2021}, author = {La Fortezza, M and Velicer, GJ}, title = {Social selection within aggregative multicellular development drives morphological evolution.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1963}, pages = {20211522}, pmid = {34814750}, issn = {1471-2954}, mesh = {*Biological Evolution ; Genotype ; *Myxococcus xanthus/genetics ; }, abstract = {Aggregative multicellular development is a social process involving complex forms of cooperation among unicellular organisms. In some aggregative systems, development culminates in the construction of spore-packed fruiting bodies and often unfolds within genetically and behaviourally diverse conspecific cellular environments. Here, we use the bacterium Myxococcus xanthus to test whether the character of the cellular environment during aggregative development shapes its morphological evolution. We manipulated the cellular composition of Myxococcus development in an experiment in which evolving populations initiated from a single ancestor repeatedly co-developed with one of several non-evolving partners-a cooperator, three cheaters and three antagonists. Fruiting body morphology was found to diversify not only as a function of partner genotype but more broadly as a function of partner social character, with antagonistic partners selecting for greater fruiting body formation than cheaters or the cooperator. Yet even small degrees of genetic divergence between distinct cheater partners sufficed to drive treatment-level morphological divergence. Co-developmental partners also determined the magnitude and dynamics of stochastic morphological diversification and subsequent convergence. In summary, we find that even just a few genetic differences affecting developmental and social features can greatly impact morphological evolution of multicellular bodies and experimentally demonstrate that microbial warfare can promote cooperation.}, } @article {pmid34811380, year = {2021}, author = {Yamashita, S and Yamamoto, K and Matsuzaki, R and Suzuki, S and Yamaguchi, H and Hirooka, S and Minakuchi, Y and Miyagishima, SY and Kawachi, M and Toyoda, A and Nozaki, H}, title = {Genome sequencing of the multicellular alga Astrephomene provides insights into convergent evolution of germ-soma differentiation.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {22231}, pmid = {34811380}, issn = {2045-2322}, support = {17J03439//Japan Society for the Promotion of Science/ ; 16H06279//Japan Society for the Promotion of Science/ ; 16H02518//Japan Society for the Promotion of Science/ ; 20H03299//Japan Society for the Promotion of Science/ ; }, mesh = {Algal Proteins/genetics/metabolism ; *Biological Evolution ; Cell Differentiation/*genetics ; Chlorophyceae/*genetics ; Chlorophyta/*genetics ; Germ Cells ; Volvox/genetics ; Whole Genome Sequencing ; }, abstract = {Germ-soma differentiation evolved independently in many eukaryotic lineages and contributed to complex multicellular organizations. However, the molecular genetic bases of such convergent evolution remain unresolved. Two multicellular volvocine green algae, Volvox and Astrephomene, exhibit convergent evolution of germ-soma differentiation. The complete genome sequence is now available for Volvox, while genome information is scarce for Astrephomene. Here, we generated the de novo whole genome sequence of Astrephomene gubernaculifera and conducted RNA-seq analysis of isolated somatic and reproductive cells. In Volvox, tandem duplication and neofunctionalization of the ancestral transcription factor gene (RLS1/rlsD) might have led to the evolution of regA, the master regulator for Volvox germ-soma differentiation. However, our genome data demonstrated that Astrephomene has not undergone tandem duplication of the RLS1/rlsD homolog or acquisition of a regA-like gene. Our RNA-seq analysis revealed the downregulation of photosynthetic and anabolic gene expression in Astrephomene somatic cells, as in Volvox. Among genes with high expression in somatic cells of Astrephomene, we identified three genes encoding putative transcription factors, which may regulate somatic cell differentiation. Thus, the convergent evolution of germ-soma differentiation in the volvocine algae may have occurred by the acquisition of different regulatory circuits that generate a similar division of labor.}, } @article {pmid34789585, year = {2021}, author = {Miller, EA and Leidholt, S and Galvin, T and Norton, A and Van Houtan, KS and Vega Thurber, R and Boustany, A}, title = {Electron microscopy reveals viral-like particles and mitochondrial degradation in scombrid puffy snout syndrome.}, journal = {Diseases of aquatic organisms}, volume = {147}, number = {}, pages = {25-31}, doi = {10.3354/dao03634}, pmid = {34789585}, issn = {0177-5103}, mesh = {Animals ; Eukaryota ; Fishes ; Microscopy, Electron/veterinary ; *Mitophagy ; *Perciformes ; }, abstract = {Aquaculture is an increasingly important food resource, but its sustainability is often limited by disease. In Scombridae fishes, puffy snout syndrome (PSS) is a debilitating condition where tumor-like collagenous growths form around the eyes, nares, and mandibles which impair vision and feeding and frequently lead to mortality. While PSS is considered an infectious or metabolic disease, no disease agents or promoters have been identified. Here, we used electron microscopy (EM) to describe the cellular pathology and search for etiological agents of PSS in Pacific mackerel Scomber japonicus, the first use of this approach for PSS. We examined aquaculture specimens across a range of apparent PSS severity, comparing the results to both wild and aquaculture asymptomatic mackerel. EM imagery consistently revealed viral-like particles in PSS samples, as well as the uniform absence of bacteria, protists, fungi, and other multicellular parasites. In addition to viral-like particles, symptomatic fish had a higher mean percentage of swollen and disintegrating mitochondria than both asymptomatic aquaculture and wild mackerel. This suggests that degraded mitochondria may be related to PSS and could be important to further understanding the origin, promoters, and prevention of PSS. This study serves as a first step in identifying the etiological agents of PSS.}, } @article {pmid34788294, year = {2021}, author = {Fortunato, A and Fleming, A and Aktipis, A and Maley, CC}, title = {Upregulation of DNA repair genes and cell extrusion underpin the remarkable radiation resistance of Trichoplax adhaerens.}, journal = {PLoS biology}, volume = {19}, number = {11}, pages = {e3001471}, pmid = {34788294}, issn = {1545-7885}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; DNA Damage/genetics/radiation effects ; DNA Repair/*genetics/radiation effects ; Gene Expression Regulation/radiation effects ; Placozoa/anatomy & histology/*genetics/radiation effects ; Radiation Exposure ; Radiation Tolerance/*genetics ; Sequence Analysis, DNA ; Up-Regulation/*genetics/radiation effects ; Whole Genome Sequencing ; X-Rays ; }, abstract = {Trichoplax adhaerens is the simplest multicellular animal with tissue differentiation and somatic cell turnover. Like all other multicellular organisms, it should be vulnerable to cancer, yet there have been no reports of cancer in T. adhaerens or any other placozoan. We investigated the cancer resistance of T. adhaerens, discovering that they are able to tolerate high levels of radiation damage (218.6 Gy). To investigate how T. adhaerens survive levels of radiation that are lethal to other animals, we examined gene expression after the X-ray exposure, finding overexpression of genes involved in DNA repair and apoptosis including the MDM2 gene. We also discovered that T. adhaerens extrudes clusters of inviable cells after X-ray exposure. T. adhaerens is a valuable model organism for studying the molecular, genetic, and tissue-level mechanisms underlying cancer suppression.}, } @article {pmid34785682, year = {2021}, author = {He, H and Wu, X and Xian, H and Zhu, J and Yang, Y and Lv, Y and Li, Y and Konhauser, KO}, title = {An abiotic source of Archean hydrogen peroxide and oxygen that pre-dates oxygenic photosynthesis.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {6611}, pmid = {34785682}, issn = {2041-1723}, mesh = {Atmosphere ; Biological Evolution ; Cyanobacteria/metabolism ; Earth, Planet ; Environment ; Hydrogen Peroxide/*chemistry/*metabolism ; Oxidation-Reduction ; Oxygen/*chemistry/*metabolism ; Particle Size ; Photosynthesis/*physiology ; }, abstract = {The evolution of oxygenic photosynthesis is a pivotal event in Earth's history because the O2 released fundamentally changed the planet's redox state and facilitated the emergence of multicellular life. An intriguing hypothesis proposes that hydrogen peroxide (H2O2) once acted as the electron donor prior to the evolution of oxygenic photosynthesis, but its abundance during the Archean would have been limited. Here, we report a previously unrecognized abiotic pathway for Archean H2O2 production that involves the abrasion of quartz surfaces and the subsequent generation of surface-bound radicals that can efficiently oxidize H2O to H2O2 and O2. We propose that in turbulent subaqueous environments, such as rivers, estuaries and deltas, this process could have provided a sufficient H2O2 source that led to the generation of biogenic O2, creating an evolutionary impetus for the origin of oxygenic photosynthesis.}, } @article {pmid34778256, year = {2021}, author = {Daignan-Fornier, B and Laporte, D and Sagot, I}, title = {Quiescence Through the Prism of Evolution.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {745069}, pmid = {34778256}, issn = {2296-634X}, abstract = {Being able to reproduce and survive is fundamental to all forms of life. In primitive unicellular organisms, the emergence of quiescence as a reversible proliferation arrest has most likely improved cell survival under unfavorable environmental conditions. During evolution, with the repeated appearances of multicellularity, several aspects of unicellular quiescence were conserved while new quiescent cell intrinsic abilities arose. We propose that the formation of a microenvironment by neighboring cells has allowed disconnecting quiescence from nutritional cues. In this new context, non-proliferative cells can stay metabolically active, potentially authorizing the emergence of new quiescent cell properties, and thereby favoring cell specialization. Through its co-evolution with cell specialization, quiescence may have been a key motor of the fascinating diversity of multicellular complexity.}, } @article {pmid34771463, year = {2021}, author = {Riol, A and Cervera, J and Levin, M and Mafe, S}, title = {Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate.}, journal = {Cancers}, volume = {13}, number = {21}, pages = {}, pmid = {34771463}, issn = {2072-6694}, support = {PGC2018-097359-B-I00//Ministerio de Ciencia e Innovación/ ; 12171//Allen Foundation/ ; TWCF0089/AB55//Templeton World Charity Foundation/ ; HR0011-18-2-0022//Defense Advanced Research Projects Agency/ ; }, abstract = {Electric potential distributions can act as instructive pre-patterns for development, regeneration, and tumorigenesis in cell systems. The biophysical states influence transcription, proliferation, cell shape, migration, and differentiation through biochemical and biomechanical downstream transduction processes. A major knowledge gap is the origin of spatial patterns in vivo, and their relationship to the ion channels and the electrical synapses known as gap junctions. Understanding this is critical for basic evolutionary developmental biology as well as for regenerative medicine. We computationally show that cells may express connexin proteins with different voltage-gated gap junction conductances as a way to maintain multicellular regions at distinct membrane potentials. We show that increasing the multicellular connectivity via enhanced junction function does not always contribute to the bioelectrical normalization of abnormally depolarized multicellular patches. From a purely electrical junction view, this result suggests that the reduction rather than the increase of specific connexin levels can also be a suitable bioelectrical approach in some cases and time stages. We offer a minimum model that incorporates effective conductances ultimately related to specific ion channel and junction proteins that are amenable to external regulation. We suggest that the bioelectrical patterns and their encoded instructive information can be externally modulated by acting on the mean fields of cell systems, a complementary approach to that of acting on the molecular characteristics of individual cells. We believe that despite the limitations of a biophysically focused model, our approach can offer useful qualitative insights into the collective dynamics of cell system bioelectricity.}, } @article {pmid34769394, year = {2021}, author = {Marijuán, PC and Navarro, J}, title = {From Molecular Recognition to the "Vehicles" of Evolutionary Complexity: An Informational Approach.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769394}, issn = {1422-0067}, mesh = {Animals ; *Biological Evolution ; Computational Biology/*methods ; Humans ; *Metabolic Networks and Pathways ; *Mutation ; Signal Transduction ; }, abstract = {Countless informational proposals and models have explored the singular characteristics of biological systems: from the initial choice of information terms in the early days of molecular biology to the current bioinformatic avalanche in this "omic" era. However, this was conducted, most often, within partial, specialized scopes or just metaphorically. In this paper, we attempt a consistent informational discourse, initially based on the molecular recognition paradigm, which addresses the main stages of biological organization in a new way. It considers the interconnection between signaling systems and information flows, between informational architectures and biomolecular codes, between controlled cell cycles and multicellular complexity. It also addresses, in a new way, a central issue: how new evolutionary paths are opened by the cumulated action of multiple variation engines or mutational 'vehicles' evolved for the genomic exploration of DNA sequence space. Rather than discussing the possible replacement, extension, or maintenance of traditional neo-Darwinian tenets, a genuine informational approach to evolutionary phenomena is advocated, in which systemic variation in the informational architectures may induce differential survival (self-construction, self-maintenance, and reproduction) of biological agents within their open ended environment.}, } @article {pmid34769071, year = {2021}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Growth of Biological Complexity from Prokaryotes to Hominids Reflected in the Human Genome.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769071}, issn = {1422-0067}, mesh = {Animals ; Epigenesis, Genetic ; *Evolution, Molecular ; *Gene Regulatory Networks ; *Genome, Human ; Hominidae/genetics ; Humans ; Multigene Family ; Oncogenes ; Prokaryotic Cells/metabolism ; Transcription Factors/genetics ; }, abstract = {The growth of complexity in evolution is a most intriguing phenomenon. Using gene phylostratigraphy, we showed this growth (as reflected in regulatory mechanisms) in the human genome, tracing the path from prokaryotes to hominids. Generally, the different regulatory gene families expanded at different times, yet only up to the Euteleostomi (bony vertebrates). The only exception was the expansion of transcription factors (TF) in placentals; however, we argue that this was not related to increase in general complexity. Surprisingly, although TF originated in the Prokaryota while chromatin appeared only in the Eukaryota, the expansion of epigenetic factors predated the expansion of TF. Signaling receptors, tumor suppressors, oncogenes, and aging- and disease-associated genes (indicating vulnerabilities in terms of complex organization and strongly enrichment in regulatory genes) also expanded only up to the Euteleostomi. The complexity-related gene properties (protein size, number of alternative splicing mRNA, length of untranslated mRNA, number of biological processes per gene, number of disordered regions in a protein, and density of TF-TF interactions) rose in multicellular organisms and declined after the Euteleostomi, and possibly earlier. At the same time, the speed of protein sequence evolution sharply increased in the genes that originated after the Euteleostomi. Thus, several lines of evidence indicate that molecular mechanisms of complexity growth were changing with time, and in the phyletic lineage leading to humans, the most salient shift occurred after the basic vertebrate body plan was fixed with bony skeleton. The obtained results can be useful for evolutionary medicine.}, } @article {pmid34752334, year = {2021}, author = {Pereira, PHS and Garcia, CRS and Bouvier, M}, title = {Identifying Plasmodium falciparum receptor activation using bioluminescence resonance energy transfer (BRET)-based biosensors in HEK293 cells.}, journal = {Methods in cell biology}, volume = {166}, number = {}, pages = {223-233}, doi = {10.1016/bs.mcb.2021.06.018}, pmid = {34752334}, issn = {0091-679X}, mesh = {*Biosensing Techniques ; Energy Transfer ; HEK293 Cells ; Humans ; *Plasmodium falciparum/metabolism ; Receptors, G-Protein-Coupled/genetics/metabolism ; }, abstract = {Throughout evolution the need for unicellular organisms to associate and form a single cluster of cells had several evolutionary advantages. G protein coupled receptors (GPCRs) are responsible for a large part of the senses that allow this clustering to succeed, playing a fundamental role in the perception of cell's external environment, enabling the interaction and coordinated development between each cell of a multicellular organism. GPCRs are not exclusive to complex multicellular organisms. In single-celled organisms, GPCRs are also present and have a similar function of detecting changes in the external environment and transforming them into a biological response. There are no reports of GPCRs in parasitic protozoa, such as the Plasmodium genus, and the identification of a protein of this family in P. falciparum would have a significant impact both on the understanding of the basic biology of the parasite and on the history of the evolution of GPCRs. The protocol described here was successfully applied to study a GPCR candidate in P. falciparum for the first time, and we hope that it helps other groups to use the same approach to study this deadly parasite.}, } @article {pmid34740967, year = {2021}, author = {Krespach, MKC and Stroe, MC and Flak, M and Komor, AJ and Nietzsche, S and Sasso, S and Hertweck, C and Brakhage, AA}, title = {Bacterial marginolactones trigger formation of algal gloeocapsoids, protective aggregates on the verge of multicellularity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {45}, pages = {}, pmid = {34740967}, issn = {1091-6490}, mesh = {*Cell Aggregation ; Chlamydomonas reinhardtii/*physiology/ultrastructure ; Macrolides/metabolism ; Microbial Interactions ; Streptomyces/metabolism ; }, abstract = {Photosynthetic microorganisms including the green alga Chlamydomonas reinhardtii are essential to terrestrial habitats as they start the carbon cycle by conversion of CO2 to energy-rich organic carbohydrates. Terrestrial habitats are densely populated, and hence, microbial interactions mediated by natural products are inevitable. We previously discovered such an interaction between Streptomyces iranensis releasing the marginolactone azalomycin F in the presence of C. reinhardtii Whether the alga senses and reacts to azalomycin F remained unknown. Here, we report that sublethal concentrations of azalomycin F trigger the formation of a protective multicellular structure by C. reinhardtii, which we named gloeocapsoid. Gloeocapsoids contain several cells which share multiple cell membranes and cell walls and are surrounded by a spacious matrix consisting of acidic polysaccharides. After azalomycin F removal, gloeocapsoid aggregates readily disassemble, and single cells are released. The presence of marginolactone biosynthesis gene clusters in numerous streptomycetes, their ubiquity in soil, and our observation that other marginolactones such as desertomycin A and monazomycin also trigger the formation of gloeocapsoids suggests a cross-kingdom competition with ecological relevance. Furthermore, gloeocapsoids allow for the survival of C. reinhardtii at alkaline pH and otherwise lethal concentrations of azalomycin F. Their structure and polysaccharide matrix may be ancestral to the complex mucilage formed by multicellular members of the Chlamydomonadales such as Eudorina and Volvox Our finding suggests that multicellularity may have evolved to endure the presence of harmful competing bacteria. Additionally, it underlines the importance of natural products as microbial cues, which initiate interesting ecological scenarios of attack and counter defense.}, } @article {pmid34740727, year = {2022}, author = {Quan, X and Kato, D and Daria, V and Matoba, O and Wake, H}, title = {Holographic microscope and its biological application.}, journal = {Neuroscience research}, volume = {179}, number = {}, pages = {57-64}, doi = {10.1016/j.neures.2021.10.012}, pmid = {34740727}, issn = {1872-8111}, mesh = {Animals ; *Holography/methods ; Mice ; Neurons/physiology ; Optogenetics/methods ; Photic Stimulation/methods ; Photons ; }, abstract = {Holographic structured illumination combined with optogenetics enables patterned stimulation of neurons and glial cells in an intact living brain. Moreover, in vivo functional imaging of cellular activity with recent advanced microscope technologies allows for visualization of the cellular responses during learning, emotion and cognition. Integrating these techniques can be used to verify the link between cell function and behavior output. However, there are technical limitations to stimulate multiple cells with high spatial and temporal resolution with available techniques of optogenetic stimulation. Here, we summarized a two-photon microscope combined with holographic system to stimulate multiple cells with high spatial and temporal resolution for living mice and their biological application.}, } @article {pmid34738176, year = {2022}, author = {Verdan, M and Resende, E and Cypriano, J and Werneck, C and Lins, U and Abreu, F}, title = {Occurrence of south- and north-seeking multicellular magnetotactic prokaryotes in a coastal lagoon in the South Hemisphere.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {25}, number = {2}, pages = {309-323}, pmid = {34738176}, issn = {1618-1905}, mesh = {Brazil ; *Deltaproteobacteria/genetics ; Matrix Metalloproteinases/genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Magnetotactic bacteria (MTB) response to the magnetic field can be classified into north-seeking (NS) and south-seeking (SS), which usually depends on their inhabiting site in the North and South Hemisphere, respectively. However, uncommon inverted polarity was observed on both hemispheres. Here, we studied magnetotactic multicellular prokaryotes (MMPs) from a coastal lagoon in Brazil collected in April and August 2014. MMPs from the first sampling period presented both magnetotactic behaviors, while MMPs collected in August/2014 were only SS. Phylogenetic analysis based on the 16S rRNA coding gene showed that these organisms belong to the Deltaproteobacteria class. The 16S rRNA gene sequences varied among MMPs regardless of the sampling period, and similarity values were not related to the type of magnetotactic response presented by the microorganisms. Therefore, differences in the magnetotactic behavior might result from the physiological state of MMPs, the availability of resources, or the instability of the chemical gradient in the environment. This is the first report of NS magnetotactic behavior on MMPs from the South Hemisphere.}, } @article {pmid34725037, year = {2021}, author = {Hakala, SM and Meurville, MP and Stumpe, M and LeBoeuf, AC}, title = {Biomarkers in a socially exchanged /fluid reflect colony maturity, behavior, and distributed metabolism.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34725037}, issn = {2050-084X}, mesh = {Animals ; Ants/metabolism/*physiology ; Biomarkers/*metabolism ; Social Behavior ; }, abstract = {In cooperative systems exhibiting division of labor, such as microbial communities, multicellular organisms, and social insect colonies, individual units share costs and benefits through both task specialization and exchanged materials. Socially exchanged fluids, like seminal fluid and milk, allow individuals to molecularly influence conspecifics. Many social insects have a social circulatory system, where food and endogenously produced molecules are transferred mouth-to-mouth (stomodeal trophallaxis), connecting all the individuals in the society. To understand how these endogenous molecules relate to colony life, we used quantitative proteomics to investigate the trophallactic fluid within colonies of the carpenter ant Camponotus floridanus. We show that different stages of the colony life cycle circulate different types of proteins: young colonies prioritize direct carbohydrate processing; mature colonies prioritize accumulation and transmission of stored resources. Further, colonies circulate proteins implicated in oxidative stress, ageing, and social insect caste determination, potentially acting as superorganismal hormones. Brood-caring individuals that are also closer to the queen in the social network (nurses) showed higher abundance of oxidative stress-related proteins. Thus, trophallaxis behavior could provide a mechanism for distributed metabolism in social insect societies. The ability to thoroughly analyze the materials exchanged between cooperative units makes social insect colonies useful models to understand the evolution and consequences of metabolic division of labor at other scales.}, } @article {pmid34721057, year = {2021}, author = {Larie, D and An, G and Cockrell, RC}, title = {The Use of Artificial Neural Networks to Forecast the Behavior of Agent-Based Models of Pathophysiology: An Example Utilizing an Agent-Based Model of Sepsis.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {716434}, pmid = {34721057}, issn = {1664-042X}, abstract = {Introduction: Disease states are being characterized at finer and finer levels of resolution via biomarker or gene expression profiles, while at the same time. Machine learning (ML) is increasingly used to analyze and potentially classify or predict the behavior of biological systems based on such characterization. As ML applications are extremely data-intensive, given the relative sparsity of biomedical data sets ML training of artificial neural networks (ANNs) often require the use of synthetic training data. Agent-based models (ABMs) that incorporate known biological mechanisms and their associated stochastic properties are a potential means of generating synthetic data. Herein we present an example of ML used to train an artificial neural network (ANN) as a surrogate system used to predict the time evolution of an ABM focusing on the clinical condition of sepsis. Methods: The disease trajectories for clinical sepsis, in terms of temporal cytokine and phenotypic dynamics, can be interpreted as a random dynamical system. The Innate Immune Response Agent-based Model (IIRABM) is a well-established model that utilizes known cellular and molecular rules to simulate disease trajectories corresponding to clinical sepsis. We have utilized two distinct neural network architectures, Long Short-Term Memory and Multi-Layer Perceptron, to take a time sequence of five measurements of eleven IIRABM simulated serum cytokine concentrations as input and to return both the future cytokine trajectories as well as an aggregate metric representing the patient's state of health. Results: The ANNs predicted model trajectories with the expected amount of error, due to stochasticity in the simulation, and recognizing that the mapping from a specific cytokine profile to a state-of-health is not unique. The Multi-Layer Perceptron neural network, generated predictions with a more accurate forecasted trajectory cone. Discussion: This work serves as a proof-of-concept for the use of ANNs to predict disease progression in sepsis as represented by an ABM. The findings demonstrate that multicellular systems with intrinsic stochasticity can be approximated with an ANN, but that forecasting a specific trajectory of the system requires sequential updating of the system state to provide a rolling forecast horizon.}, } @article {pmid34716269, year = {2021}, author = {Yang, H and Pegoraro, AF and Han, Y and Tang, W and Abeyaratne, R and Bi, D and Guo, M}, title = {Configurational fingerprints of multicellular living systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {44}, pages = {}, pmid = {34716269}, issn = {1091-6490}, support = {R01 GM140108/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biophysical Phenomena/*physiology ; Cell Cycle ; Cell Movement ; Cell Proliferation ; Epithelial Cells/cytology ; Humans ; Image Processing, Computer-Assisted/*methods ; Morphogenesis ; Neoplasms ; Organ Specificity/*physiology ; *Phase Transition ; Spheroids, Cellular/cytology ; Wound Healing ; }, abstract = {Cells cooperate as groups to achieve structure and function at the tissue level, during which specific material characteristics emerge. Analogous to phase transitions in classical physics, transformations in the material characteristics of multicellular assemblies are essential for a variety of vital processes including morphogenesis, wound healing, and cancer. In this work, we develop configurational fingerprints of particulate and multicellular assemblies and extract volumetric and shear order parameters based on this fingerprint to quantify the system disorder. Theoretically, these two parameters form a complete and unique pair of signatures for the structural disorder of a multicellular system. The evolution of these two order parameters offers a robust and experimentally accessible way to map the phase transitions in expanding cell monolayers and during embryogenesis and invasion of epithelial spheroids.}, } @article {pmid34716098, year = {2022}, author = {Bogaert, KA and Blomme, J and Beeckman, T and De Clerck, O}, title = {Auxin's origin: do PILS hold the key?.}, journal = {Trends in plant science}, volume = {27}, number = {3}, pages = {227-236}, doi = {10.1016/j.tplants.2021.09.008}, pmid = {34716098}, issn = {1878-4372}, mesh = {Biological Transport ; *Indoleacetic Acids/metabolism ; *Membrane Transport Proteins/genetics/metabolism ; Plants/genetics/metabolism ; }, abstract = {Auxin is a key regulator of many developmental processes in land plants and plays a strikingly similar role in the phylogenetically distant brown seaweeds. Emerging evidence shows that the PIN and PIN-like (PILS) auxin transporter families have preceded the evolution of the canonical auxin response pathway. A wide conservation of PILS-mediated auxin transport, together with reports of auxin function in unicellular algae, would suggest that auxin function preceded the advent of multicellularity. We find that PIN and PILS transporters form two eukaryotic subfamilies within a larger bacterial family. We argue that future functional characterisation of algal PIN and PILS transporters can shed light on a common origin of an auxin function followed by independent co-option in a multicellular context.}, } @article {pmid34714532, year = {2022}, author = {Cao, Y}, title = {Neural is Fundamental: Neural Stemness as the Ground State of Cell Tumorigenicity and Differentiation Potential.}, journal = {Stem cell reviews and reports}, volume = {18}, number = {1}, pages = {37-55}, pmid = {34714532}, issn = {2629-3277}, mesh = {Carcinogenesis/genetics ; Cell Differentiation/genetics ; *Germ Layers ; Humans ; *Neural Stem Cells ; }, abstract = {Tumorigenic cells are similar to neural stem cells or embryonic neural cells in regulatory networks, tumorigenicity and pluripotent differentiation potential. By integrating the evidence from developmental biology, tumor biology and evolution, I will make a detailed discussion on the observations and propose that neural stemness underlies two coupled cell properties, tumorigenicity and pluripotent differentiation potential. Neural stemness property of tumorigenic cells can hopefully integrate different observations/concepts underlying tumorigenesis. Neural stem cells and tumorigenic cells share regulatory networks; both exhibit neural stemness, tumorigenicity and pluripotent differentiation potential; both depend on expression or activation of ancestral genes; both rely primarily on aerobic glycolytic metabolism; both can differentiate into various cells/tissues that are derived from three germ layers, leading to tumor formation resembling severely disorganized or more degenerated process of embryonic tissue differentiation; both are enriched in long genes with more splice variants that provide more plastic scaffolds for cell differentiation, etc. Neural regulatory networks, which include higher levels of basic machineries of cell physiological functions and developmental programs, work concertedly to define a basic state with fast cell cycle and proliferation. This is predestined by the evolutionary advantage of neural state, the ground or initial state for multicellularity with adaptation to an ancient environment. Tumorigenesis might represent a process of restoration of neural ground state, thereby restoring a state with fast proliferation and pluripotent differentiation potential in somatic cells. Tumorigenesis and pluripotent differentiation potential might be better understood from understanding neural stemness, and cancer therapy should benefit more from targeting neural stemness.}, } @article {pmid34711923, year = {2021}, author = {Wan, X and Saito, JA and Hou, S and Geib, SM and Yuryev, A and Higa, LM and Womersley, CZ and Alam, M}, title = {The Aphelenchus avenae genome highlights evolutionary adaptation to desiccation.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {1232}, pmid = {34711923}, issn = {2399-3642}, mesh = {Adaptation, Biological/*physiology ; Animals ; Biological Evolution ; *Desiccation ; Gene Duplication/physiology ; Gene Expression Profiling ; Helminth Proteins/*genetics/metabolism ; Humidity ; Phosphotransferases/*genetics/metabolism ; Tylenchida/enzymology/*genetics ; Water/*metabolism ; }, abstract = {Some organisms can withstand complete body water loss (losing up to 99% of body water) and stay in ametabolic state for decades until rehydration, which is known as anhydrobiosis. Few multicellular eukaryotes on their adult stage can withstand life without water. We still have an incomplete understanding of the mechanism for metazoan survival of anhydrobiosis. Here we report the 255-Mb genome of Aphelenchus avenae, which can endure relative zero humidity for years. Gene duplications arose genome-wide and contributed to the expansion and diversification of 763 kinases, which represents the second largest metazoan kinome to date. Transcriptome analyses of ametabolic state of A. avenae indicate the elevation of ATP level for global recycling of macromolecules and enhancement of autophagy in the early stage of anhydrobiosis. We catalogue 74 species-specific intrinsically disordered proteins, which may facilitate A. avenae to survive through desiccation stress. Our findings refine a molecular basis evolving for survival in extreme water loss and open the way for discovering new anti-desiccation strategies.}, } @article {pmid34699573, year = {2021}, author = {Tanno, A and Tokutsu, R and Arakaki, Y and Ueki, N and Minagawa, J and Yoshimura, K and Hisabori, T and Nozaki, H and Wakabayashi, KI}, title = {The four-celled Volvocales green alga Tetrabaena socialis exhibits weak photobehavior and high-photoprotection ability.}, journal = {PloS one}, volume = {16}, number = {10}, pages = {e0259138}, pmid = {34699573}, issn = {1932-6203}, mesh = {Chlorophyta/*physiology ; Photic Stimulation ; Phototropism/*physiology ; Volvox/*physiology ; }, abstract = {Photo-induced behavioral responses (photobehaviors) are crucial to the survival of motile phototrophic organisms in changing light conditions. Volvocine green algae are excellent model organisms for studying the regulatory mechanisms of photobehavior. We recently reported that unicellular Chlamydomonas reinhardtii and multicellular Volvox rousseletii exhibit similar photobehaviors, such as phototactic and photoshock responses, via different ciliary regulations. To clarify how the regulatory systems have changed during the evolution of multicellularity, we investigated the photobehaviors of four-celled Tetrabaena socialis. Surprisingly, unlike C. reinhardtii and V. rousseletii, T. socialis did not exhibit immediate photobehaviors after light illumination. Electrophysiological analysis revealed that the T. socialis eyespot does not function as a photoreceptor. Instead, T. socialis exhibited slow accumulation toward the light source in a photosynthesis-dependent manner. Our assessment of photosynthetic activities showed that T. socialis chloroplasts possess higher photoprotection abilities against strong light than C. reinhardtii. These data suggest that C. reinhardtii and T. socialis employ different strategies to avoid high-light stress (moving away rapidly and gaining photoprotection, respectively) despite their close phylogenetic relationship.}, } @article {pmid34695730, year = {2021}, author = {Grochau-Wright, ZI and Ferris, PJ and Tumberger, J and Jiménez-Marin, B and Olson, BJSC and Michod, RE}, title = {Characterization and Transformation of reg Cluster Genes in Volvox powersii Enable Investigation of Convergent Evolution of Cellular Differentiation in Volvox.}, journal = {Protist}, volume = {172}, number = {5-6}, pages = {125834}, doi = {10.1016/j.protis.2021.125834}, pmid = {34695730}, issn = {1618-0941}, support = {GT11065/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Base Sequence ; Cell Differentiation ; *Chlorophyta ; *Volvox/genetics ; }, abstract = {The evolution of germ-soma cellular differentiation represents a key step in the evolution of multicellular individuality. Volvox carteri and its relatives, the volvocine green algae, provide a model system for studying the evolution of cellular differentiation. In V. carteri, the regA gene controls somatic cell differentiation and is found in a group of paralogs called the reg cluster, along with rlsA, rlsB, and rlsC. However, the developmental program of V. carteri is derived compared to other volvocine algae. Here we examine Volvox powersii which possesses an ancestral developmental program and independent evolution of the Volvox body plan. We sequenced the reg cluster from V. powersii wild-type and a mutant with fewer cells and altered germ-soma ratio. We found that the mutant strain's rlsB gene has a deletion predicted to cause a truncated protein product. We developed a genetic transformation procedure to insert wild-type rlsB into the mutant strain. Transformation did not result in phenotypic rescue, suggesting the rlsB mutation is insufficient for generating the mutant phenotype. The transformation techniques and sequences described here provide essential tools to study V. powersii, a species well suited for studying the evolution of cellular differentiation and convergent evolution of Volvox morphology.}, } @article {pmid34685730, year = {2021}, author = {Ni, Z and Cheng, X}, title = {Origin and Isoform Specific Functions of Exchange Proteins Directly Activated by cAMP: A Phylogenetic Analysis.}, journal = {Cells}, volume = {10}, number = {10}, pages = {}, pmid = {34685730}, issn = {2073-4409}, support = {R35 GM122536/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Conserved Sequence ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Evolution, Molecular ; Guanine Nucleotide Exchange Factors/chemistry/*metabolism ; Humans ; *Phylogeny ; Protein Domains ; Protein Isoforms/chemistry/metabolism ; }, abstract = {Exchange proteins directly activated by cAMP (EPAC1 and EPAC2) are one of the several families of cellular effectors of the prototypical second messenger cAMP. To understand the origin and molecular evolution of EPAC proteins, we performed a comprehensive phylogenetic analysis of EPAC1 and EPAC2. Our study demonstrates that unlike its cousin PKA, EPAC proteins are only present in multicellular Metazoa. Within the EPAC family, EPAC1 is only associated with chordates, while EPAC2 spans the entire animal kingdom. Despite a much more contemporary origin, EPAC1 proteins show much more sequence diversity among species, suggesting that EPAC1 has undergone more selection and evolved faster than EPAC2. Phylogenetic analyses of the individual cAMP binding domain (CBD) and guanine nucleotide exchange (GEF) domain of EPACs, two most conserved regions between the two isoforms, further reveal that EPAC1 and EPAC2 are closely clustered together within both the larger cyclic nucleotide receptor and RAPGEF families. These results support the notion that EPAC1 and EPAC2 share a common ancestor resulting from a fusion between the CBD of PKA and the GEF from RAPGEF1. On the other hand, the two terminal extremities and the RAS-association (RA) domains show the most sequence diversity between the two isoforms. Sequence diversities within these regions contribute significantly to the isoform-specific functions of EPACs. Importantly, unique isoform-specific sequence motifs within the RA domain have been identified.}, } @article {pmid34683464, year = {2021}, author = {Whitworth, DE and Sydney, N and Radford, EJ}, title = {Myxobacterial Genomics and Post-Genomics: A Review of Genome Biology, Genome Sequences and Related 'Omics Studies.}, journal = {Microorganisms}, volume = {9}, number = {10}, pages = {}, pmid = {34683464}, issn = {2076-2607}, abstract = {Myxobacteria are fascinating and complex microbes. They prey upon other members of the soil microbiome by secreting antimicrobial proteins and metabolites, and will undergo multicellular development if starved. The genome sequence of the model myxobacterium Myxococcus xanthus DK1622 was published in 2006 and 15 years later, 163 myxobacterial genome sequences have now been made public. This explosion in genomic data has enabled comparative genomics analyses to be performed across the taxon, providing important insights into myxobacterial gene conservation and evolution. The availability of myxobacterial genome sequences has allowed system-wide functional genomic investigations into entire classes of genes. It has also enabled post-genomic technologies to be applied to myxobacteria, including transcriptome analyses (microarrays and RNA-seq), proteome studies (gel-based and gel-free), investigations into protein-DNA interactions (ChIP-seq) and metabolism. Here, we review myxobacterial genome sequencing, and summarise the insights into myxobacterial biology that have emerged as a result. We also outline the application of functional genomics and post-genomic approaches in myxobacterial research, highlighting important findings to emerge from seminal studies. The review also provides a comprehensive guide to the genomic datasets available in mid-2021 for myxobacteria (including 24 genomes that we have sequenced and which are described here for the first time).}, } @article {pmid34681022, year = {2021}, author = {Luna, SK and Chain, FJJ}, title = {Lineage-Specific Genes and Family Expansions in Dictyostelid Genomes Display Expression Bias and Evolutionary Diversification during Development.}, journal = {Genes}, volume = {12}, number = {10}, pages = {}, pmid = {34681022}, issn = {2073-4425}, support = {R15 GM134498/GM/NIGMS NIH HHS/United States ; }, mesh = {Dictyostelium/*genetics/growth & development ; *Evolution, Molecular ; Gene Duplication/genetics ; Gene Expression Regulation, Developmental/genetics ; Genome/genetics ; *Phylogeny ; Species Specificity ; }, abstract = {Gene duplications generate new genes that can contribute to expression changes and the evolution of new functions. Genomes often consist of gene families that undergo expansions, some of which occur in specific lineages that reflect recent adaptive diversification. In this study, lineage-specific genes and gene family expansions were studied across five dictyostelid species to determine when and how they are expressed during multicellular development. Lineage-specific genes were found to be enriched among genes with biased expression (predominant expression in one developmental stage) in each species and at most developmental time points, suggesting independent functional innovations of new genes throughout the phylogeny. Biased duplicate genes had greater expression divergence than their orthologs and paralogs, consistent with subfunctionalization or neofunctionalization. Lineage-specific expansions in particular had biased genes with both molecular signals of positive selection and high expression, suggesting adaptive genetic and transcriptional diversification following duplication. Our results present insights into the potential contributions of lineage-specific genes and families in generating species-specific phenotypes during multicellular development in dictyostelids.}, } @article {pmid34680926, year = {2021}, author = {Cock, JM}, title = {Evolution of Multicellularity.}, journal = {Genes}, volume = {12}, number = {10}, pages = {}, pmid = {34680926}, issn = {2073-4425}, mesh = {Eukaryota/classification/cytology/genetics ; *Evolution, Molecular ; Phylogeny ; }, abstract = {The emergence of multicellular organisms was, perhaps, the most spectacular of the major transitions during the evolutionary history of life on this planet [...].}, } @article {pmid34671319, year = {2021}, author = {Quinting, T and Heymann, AK and Bicker, A and Nauth, T and Bernardini, A and Hankeln, T and Fandrey, J and Schreiber, T}, title = {Myoglobin Protects Breast Cancer Cells Due to Its ROS and NO Scavenging Properties.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {732190}, pmid = {34671319}, issn = {1664-2392}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Cell Survival/drug effects/genetics ; Female ; Free Radical Scavengers/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Knockdown Techniques ; Humans ; Myoglobin/genetics/metabolism/*physiology ; Nitric Oxide/*metabolism ; Protective Agents/metabolism ; RNA, Small Interfering/pharmacology ; Reactive Oxygen Species/*metabolism ; Signal Transduction/drug effects/genetics ; Tumor Cells, Cultured ; }, abstract = {Myoglobin (MB) is an oxygen-binding protein usually found in cardiac myocytes and skeletal muscle fibers. It may function as a temporary storage and transport protein for O2 but could also have scavenging capacity for reactive oxygen and nitrogen species. In addition, MB has recently been identified as a hallmark in luminal breast cancer and was shown to be robustly induced under hypoxia. Cellular responses to hypoxia are regulated by the transcription factor hypoxia-inducible factor (HIF). For exploring the function of MB in breast cancer, we employed the human cell line MDA-MB-468. Cells were grown in monolayer or as 3D multicellular spheroids, which mimic the in vivo avascular tumor architecture and physiology with a heterogeneous cell population of proliferating cells in the rim and non-cycling or necrotic cells in the core region. This central necrosis was increased after MB knockdown, indicating a role for MB in hypoxic tumor regions. In addition, MB knockdown caused higher levels of HIF-1α protein after treatment with NO, which also plays an important role in cancer cell survival. MB knockdown also led to higher reactive oxygen species (ROS) levels in the cells after treatment with H2O2. To further explore the role of MB in cell survival, we performed RNA-Seq after MB knockdown and NO treatment. 1029 differentially expressed genes (DEGs), including 45 potential HIF-1 target genes, were annotated in regulatory pathways that modulate cellular function and maintenance, cell death and survival, and carbohydrate metabolism. Of these target genes, TMEFF1, TREX2, GLUT-1, MKNK-1, and RAB8B were significantly altered. Consistently, a decreased expression of GLUT-1, MKNK-1, and RAB8B after MB knockdown was confirmed by qPCR. All three genes of interest are often up regulated in cancer and correlate with a poor clinical outcome. Thus, our data indicate that myoglobin might influence the survival of breast cancer cells, possibly due to its ROS and NO scavenging properties and could be a valuable target for cancer therapy.}, } @article {pmid34665225, year = {2021}, author = {Zagoskin, MV and Wang, J}, title = {Programmed DNA elimination: silencing genes and repetitive sequences in somatic cells.}, journal = {Biochemical Society transactions}, volume = {49}, number = {5}, pages = {1891-1903}, pmid = {34665225}, issn = {1470-8752}, support = {R01 AI155588/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Chromosomes/genetics ; DNA Transposable Elements/*genetics ; Embryonic Development/genetics ; Evolution, Molecular ; Gene Expression ; Gene Expression Regulation ; *Gene Silencing ; Germ Cells ; Humans ; }, abstract = {In a multicellular organism, the genomes of all cells are in general the same. Programmed DNA elimination is a notable exception to this genome constancy rule. DNA elimination removes genes and repetitive elements in the germline genome to form a reduced somatic genome in various organisms. The process of DNA elimination within an organism is highly accurate and reproducible; it typically occurs during early embryogenesis, coincident with germline-soma differentiation. DNA elimination provides a mechanism to silence selected genes and repeats in somatic cells. Recent studies in nematodes suggest that DNA elimination removes all chromosome ends, resolves sex chromosome fusions, and may also promote the birth of novel genes. Programmed DNA elimination processes are diverse among species, suggesting DNA elimination likely has evolved multiple times in different taxa. The growing list of organisms that undergo DNA elimination indicates that DNA elimination may be more widespread than previously appreciated. These various organisms will serve as complementary and comparative models to study the function, mechanism, and evolution of programmed DNA elimination in metazoans.}, } @article {pmid34661335, year = {2022}, author = {Stüeken, EE and Viehmann, S and Hohl, SV}, title = {Contrasting nutrient availability between marine and brackish waters in the late Mesoproterozoic: Evidence from the Paranoá Group, Brazil.}, journal = {Geobiology}, volume = {20}, number = {2}, pages = {159-174}, doi = {10.1111/gbi.12478}, pmid = {34661335}, issn = {1472-4669}, mesh = {Brazil ; *Ecosystem ; Eukaryota ; Nutrients ; *Seawater ; }, abstract = {Understanding the delayed rise of eukaryotic life on Earth is one of the most fundamental questions about biological evolution. Numerous studies have presented evidence for oxygen and nutrient limitations in seawater during the Mesoproterozoic era, indicating that open marine settings may not have been able to sustain a eukaryotic biosphere with complex, multicellular organisms. However, many of these data sets represent restricted marine basins, which may bias our view of habitability. Furthermore, it remains untested whether rivers could have supplied significant nutrient fluxes to coastal habitats. To better characterize the sources of the major nutrients nitrogen and phosphorus, we turned to the late Mesoproterozoic Paranoá Group in Brazil (~1.1 Ga), which was deposited on a passive margin of the São Francisco craton. We present carbon, nitrogen and sulphur isotope data from an open shelf setting (Fazenda Funil) and from a brackish-water environment with significant riverine input (São Gabriel). Our results show that waters were well-oxygenated and nitrate was bioavailable in the open ocean setting at Fazenda Funil; the redoxcline appears to have been deeper and further offshore compared to restricted marine basins elsewhere in the Mesoproterozoic. In contrast, the brackish site at São Gabriel received only limited input of marine nitrate and sulphate. Nevertheless, previous reports of acritarchs reveal that this brackish-water setting was habitable to eukaryotic life. Paired with previously published cadmium isotope data, which can be used as a proxy for phosphorus cycling, our results suggest that complex organisms were perhaps not strictly dependent on marine nutrient supplies. Riverine influxes of P and possibly other nutrients likely rendered coastal waters perhaps equally habitable to the Mesoproterozoic open ocean. This conclusion supports the notion that eukaryotic organisms may have thrived in brackish or perhaps even freshwater environments.}, } @article {pmid34661162, year = {2021}, author = {Koya, J and Saito, Y and Kameda, T and Kogure, Y and Yuasa, M and Nagasaki, J and McClure, MB and Shingaki, S and Tabata, M and Tahira, Y and Akizuki, K and Kamiunten, A and Sekine, M and Shide, K and Kubuki, Y and Hidaka, T and Kitanaka, A and Nakano, N and Utsunomiya, A and Togashi, Y and Ogawa, S and Shimoda, K and Kataoka, K}, title = {Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1.}, journal = {Blood cancer discovery}, volume = {2}, number = {5}, pages = {450-467}, pmid = {34661162}, issn = {2643-3249}, mesh = {Animals ; Carcinogenesis/genetics ; Ecosystem ; *Human T-lymphotropic virus 1/genetics ; *Leukemia-Lymphoma, Adult T-Cell/genetics ; Mice ; Single-Cell Analysis ; }, abstract = {UNLABELLED: Premalignant clonal expansion of human T-cell leukemia virus type-1 (HTLV-1)-infected cells occurs before viral carcinogenesis. Here we characterize premalignant cells and the multicellular ecosystem in HTLV-1 infection with and without adult T-cell leukemia/lymphoma (ATL) by genome sequencing and single-cell simultaneous transcriptome and T/B-cell receptor sequencing with surface protein analysis. We distinguish malignant phenotypes caused by HTLV-1 infection and leukemogenesis and dissect clonal evolution of malignant cells with different clinical behavior. Within HTLV-1-infected cells, a regulatory T-cell phenotype associates with premalignant clonal expansion. We also delineate differences between virus- and tumor-related changes in the nonmalignant hematopoietic pool, including tumor-specific myeloid propagation. In a newly generated conditional knockout mouse model recapitulating T-cell-restricted CD274 (encoding PD-L1) gene lesions found in ATL, we demonstrate that PD-L1 overexpressed by T cells is transferred to surrounding cells, leading to their PD-L1 upregulation. Our findings provide insights into clonal evolution and immune landscape of multistep virus carcinogenesis.

SIGNIFICANCE: Our multimodal single-cell analyses comprehensively dissect the cellular and molecular alterations of the peripheral blood in HTLV-1 infection, with and without progression to leukemia. This study not only sheds light on premalignant clonal expansion in viral carcinogenesis, but also helps to devise novel diagnostic and therapeutic strategies for HTLV-1-related disorders.}, } @article {pmid34648394, year = {2021}, author = {Simpson, C}, title = {Adaptation to a Viscous Snowball Earth Ocean as a Path to Complex Multicellularity.}, journal = {The American naturalist}, volume = {198}, number = {5}, pages = {590-609}, doi = {10.1086/716634}, pmid = {34648394}, issn = {1537-5323}, mesh = {Acclimatization ; Fungi ; *Ice Cover ; *Seawater ; Viscosity ; }, abstract = {AbstractAnimals, fungi, and algae with complex multicellular bodies all evolved independently from unicellular ancestors. The early history of these major eukaryotic multicellular clades, if not their origins, co-occur with an extreme phase of global glaciations known as the Snowball Earth. Here, I propose that the long-term loss of low-viscosity environments due to several rounds global glaciation drove the multiple origins of complex multicellularity in eukaryotes and the subsequent radiation of complex multicellular groups into previously unoccupied niches. In this scenario, life adapts to Snowball Earth oceans by evolving large size and faster speeds through multicellularity, which acts to compensate for high-viscosity seawater and achieve fluid flow at sufficient levels to satisfy metabolic needs. Warm, low-viscosity seawater returned with the melting of the Snowball glaciers, and with it, by virtue of large and fast multicellular bodies, new ways of life were unveiled.}, } @article {pmid34643506, year = {2021}, author = {Gao, Y and Park, HJ and Traulsen, A and Pichugin, Y}, title = {Evolution of irreversible somatic differentiation.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34643506}, issn = {2050-084X}, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation ; *Cell Division ; *Cell Lineage ; Gene Expression Regulation ; Germ Cells/*physiology ; *Models, Biological ; Phenotype ; }, abstract = {A key innovation emerging in complex animals is irreversible somatic differentiation: daughters of a vegetative cell perform a vegetative function as well, thus, forming a somatic lineage that can no longer be directly involved in reproduction. Primitive species use a different strategy: vegetative and reproductive tasks are separated in time rather than in space. Starting from such a strategy, how is it possible to evolve life forms which use some of their cells exclusively for vegetative functions? Here, we develop an evolutionary model of development of a simple multicellular organism and find that three components are necessary for the evolution of irreversible somatic differentiation: (i) costly cell differentiation, (ii) vegetative cells that significantly improve the organism's performance even if present in small numbers, and (iii) large enough organism size. Our findings demonstrate how an egalitarian development typical for loose cell colonies can evolve into germ-soma differentiation dominating metazoans.}, } @article {pmid34641578, year = {2021}, author = {Wofford, HA and Myers-Dean, J and Vogel, BA and Alamo, KAE and Longshore-Neate, FA and Jagodzinski, F and Amacher, JF}, title = {Domain Analysis and Motif Matcher (DAMM): A Program to Predict Selectivity Determinants in Monosiga brevicollis PDZ Domains Using Human PDZ Data.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {19}, pages = {}, pmid = {34641578}, issn = {1420-3049}, support = {CHE-1904711//National Science Foundation/ ; }, mesh = {Amino Acid Sequence ; Choanoflagellata/*chemistry/*metabolism ; Computational Biology/*methods ; Evolution, Molecular ; Humans ; *PDZ Domains ; Phylogeny ; *Protein Binding ; Protein Conformation ; Signal Transduction ; Software ; Substrate Specificity ; }, abstract = {Choanoflagellates are single-celled eukaryotes with complex signaling pathways. They are considered the closest non-metazoan ancestors to mammals and other metazoans and form multicellular-like states called rosettes. The choanoflagellate Monosiga brevicollis contains over 150 PDZ domains, an important peptide-binding domain in all three domains of life (Archaea, Bacteria, and Eukarya). Therefore, an understanding of PDZ domain signaling pathways in choanoflagellates may provide insight into the origins of multicellularity. PDZ domains recognize the C-terminus of target proteins and regulate signaling and trafficking pathways, as well as cellular adhesion. Here, we developed a computational software suite, Domain Analysis and Motif Matcher (DAMM), that analyzes peptide-binding cleft sequence identity as compared with human PDZ domains and that can be used in combination with literature searches of known human PDZ-interacting sequences to predict target specificity in choanoflagellate PDZ domains. We used this program, protein biochemistry, fluorescence polarization, and structural analyses to characterize the specificity of A9UPE9_MONBE, a M. brevicollis PDZ domain-containing protein with no homology to any metazoan protein, finding that its PDZ domain is most similar to those of the DLG family. We then identified two endogenous sequences that bind A9UPE9 PDZ with <100 μM affinity, a value commonly considered the threshold for cellular PDZ-peptide interactions. Taken together, this approach can be used to predict cellular targets of previously uncharacterized PDZ domains in choanoflagellates and other organisms. Our data contribute to investigations into choanoflagellate signaling and how it informs metazoan evolution.}, } @article {pmid34639193, year = {2021}, author = {Siletsky, SA and Borisov, VB}, title = {Proton Pumping and Non-Pumping Terminal Respiratory Oxidases: Active Sites Intermediates of These Molecular Machines and Their Derivatives.}, journal = {International journal of molecular sciences}, volume = {22}, number = {19}, pages = {}, pmid = {34639193}, issn = {1422-0067}, support = {18-04-00503 and 19-04-00094//Russian Foundation for Basic Research/ ; }, mesh = {Catalysis ; Catalytic Domain ; Electron Transport ; Oxidoreductases/chemistry/*metabolism ; Proton Pumps/chemistry/*metabolism ; *Protons ; }, abstract = {Terminal respiratory oxidases are highly efficient molecular machines. These most important bioenergetic membrane enzymes transform the energy of chemical bonds released during the transfer of electrons along the respiratory chains of eukaryotes and prokaryotes from cytochromes or quinols to molecular oxygen into a transmembrane proton gradient. They participate in regulatory cascades and physiological anti-stress reactions in multicellular organisms. They also allow microorganisms to adapt to low-oxygen conditions, survive in chemically aggressive environments and acquire antibiotic resistance. To date, three-dimensional structures with atomic resolution of members of all major groups of terminal respiratory oxidases, heme-copper oxidases, and bd-type cytochromes, have been obtained. These groups of enzymes have different origins and a wide range of functional significance in cells. At the same time, all of them are united by a catalytic reaction of four-electron reduction in oxygen into water which proceeds without the formation and release of potentially dangerous ROS from active sites. The review analyzes recent structural and functional studies of oxygen reduction intermediates in the active sites of terminal respiratory oxidases, the features of catalytic cycles, and the properties of the active sites of these enzymes.}, } @article {pmid34636664, year = {2021}, author = {Lin, Y and Alstrup, M and Pang, JKY and Maróti, G and Er-Rafik, M and Tourasse, N and Økstad, OA and Kovács, ÁT}, title = {Adaptation of Bacillus thuringiensis to Plant Colonization Affects Differentiation and Toxicity.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0086421}, pmid = {34636664}, issn = {2379-5077}, support = {//Chinese Scholarship Council/ ; LP2020-5/2020//Lendulet-Programme/ ; }, abstract = {The Bacillus cereus group (Bacillus cereus sensu lato) has a diverse ecology, including various species that are vertebrate or invertebrate pathogens. Few isolates from the B. cereus group have however been demonstrated to benefit plant growth. Therefore, it is crucial to explore how bacterial development and pathogenesis evolve during plant colonization. Herein, we investigated Bacillus thuringiensis (Cry[-]) adaptation to the colonization of Arabidopsis thaliana roots and monitored changes in cellular differentiation in experimentally evolved isolates. Isolates from two populations displayed improved iterative ecesis on roots and increased virulence against insect larvae. Molecular dissection and recreation of a causative mutation revealed the importance of a nonsense mutation in the rho transcription terminator gene. Transcriptome analysis revealed how Rho impacts various B. thuringiensis genes involved in carbohydrate metabolism and virulence. Our work suggests that evolved multicellular aggregates have a fitness advantage over single cells when colonizing plants, creating a trade-off between swimming and multicellularity in evolved lineages, in addition to unrelated alterations in pathogenicity. IMPORTANCE Biologicals-based plant protection relies on the use of safe microbial strains. During application of biologicals to the rhizosphere, microbes adapt to the niche, including genetic mutations shaping the physiology of the cells. Here, the experimental evolution of Bacillus thuringiensis lacking the insecticide crystal toxins was examined on the plant root to reveal how adaptation shapes the differentiation of this bacterium. Interestingly, evolution of certain lineages led to increased hemolysis and insect larva pathogenesis in B. thuringiensis driven by transcriptional rewiring. Further, our detailed study reveals how inactivation of the transcription termination protein Rho promotes aggregation on the plant root in addition to altered differentiation and pathogenesis in B. thuringiensis.}, } @article {pmid34635955, year = {2021}, author = {Schneider, C}, title = {Tuft cell integration of luminal states and interaction modules in tissues.}, journal = {Pflugers Archiv : European journal of physiology}, volume = {473}, number = {11}, pages = {1713-1722}, pmid = {34635955}, issn = {1432-2013}, mesh = {Animals ; Chemoreceptor Cells/*physiology ; Epithelial Cells/*physiology ; Humans ; Immunity, Innate/physiology ; }, abstract = {Chemosensory processes are integral to the physiology of most organisms. This function is typically performed by specialized cells that are able to detect input signals and to convert them to an output dedicated to a particular group of target cells. Tuft cells are cholinergic chemosensory epithelial cells capable of producing immunologically relevant effector molecules. They are scattered throughout endoderm-derived hollow organs and function as sensors of luminal stimuli, which has been best studied in mucosal barrier epithelia. Given their epithelial origin and broad distribution, and based on their interplay with immune pathways, tuft cells can be considered a prototypical example of how complex multicellular organisms engage innate immune mechanisms to modulate and optimize organ physiology. In this review, I provide a concise overview of tuft cells and discuss how these cells influence organ adaptation to dynamic luminal conditions.}, } @article {pmid34628994, year = {2021}, author = {Caetano-Anollés, G and Aziz, MF and Mughal, F and Caetano-Anollés, D}, title = {Tracing protein and proteome history with chronologies and networks: folding recapitulates evolution.}, journal = {Expert review of proteomics}, volume = {18}, number = {10}, pages = {863-880}, doi = {10.1080/14789450.2021.1992277}, pmid = {34628994}, issn = {1744-8387}, mesh = {*Evolution, Molecular ; Genomics ; Humans ; Phylogeny ; Protein Folding ; *Proteome/genetics ; }, abstract = {INTRODUCTION: While the origin and evolution of proteins remain mysterious, advances in evolutionary genomics and systems biology are facilitating the historical exploration of the structure, function and organization of proteins and proteomes. Molecular chronologies are series of time events describing the history of biological systems and subsystems and the rise of biological innovations. Together with time-varying networks, these chronologies provide a window into the past.

AREAS COVERED: Here, we review molecular chronologies and networks built with modern methods of phylogeny reconstruction. We discuss how chronologies of structural domain families uncover the explosive emergence of metabolism, the late rise of translation, the co-evolution of ribosomal proteins and rRNA, and the late development of the ribosomal exit tunnel; events that coincided with a tendency to shorten folding time. Evolving networks described the early emergence of domains and a late 'big bang' of domain combinations.

EXPERT OPINION: Two processes, folding and recruitment appear central to the evolutionary progression. The former increases protein persistence. The later fosters diversity. Chronologically, protein evolution mirrors folding by combining supersecondary structures into domains, developing translation machinery to facilitate folding speed and stability, and enhancing structural complexity by establishing long-distance interactions in novel structural and architectural designs.}, } @article {pmid34596678, year = {2021}, author = {Schiller, EA and Bergstralh, DT}, title = {Interaction between Discs large and Pins/LGN/GPSM2: a comparison across species.}, journal = {Biology open}, volume = {10}, number = {11}, pages = {}, pmid = {34596678}, issn = {2046-6390}, support = {R01 GM125839/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Batrachoidiformes/genetics ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/metabolism ; Carrier Proteins/*metabolism ; Cell Cycle Proteins/*metabolism ; Cell Division/*genetics ; Cnidaria/genetics ; Drosophila Proteins/metabolism ; Guanylate Kinases/metabolism ; Phylogeny ; Spindle Apparatus/*metabolism ; }, abstract = {The orientation of the mitotic spindle determines the direction of cell division, and therefore contributes to tissue shape and cell fate. Interaction between the multifunctional scaffolding protein Discs large (Dlg) and the canonical spindle orienting factor GPSM2 (called Pins in Drosophila and LGN in vertebrates) has been established in bilaterian models, but its function remains unclear. We used a phylogenetic approach to test whether the interaction is obligate in animals, and in particular whether Pins/LGN/GPSM2 evolved in multicellular organisms as a Dlg-binding protein. We show that Dlg diverged in C. elegans and the syncytial sponge Opsacas minuta and propose that this divergence may correspond with differences in spindle orientation requirements between these organisms and the canonical pathways described in bilaterians. We also demonstrate that Pins/LGN/GPSM2 is present in basal animals, but the established Dlg-interaction site cannot be found in either Placozoa or Porifera. Our results suggest that the interaction between Pins/LGN/GPSM2 and Dlg appeared in Cnidaria, and we therefore speculate that it may have evolved to promote accurate division orientation in the nervous system. This work reveals the evolutionary history of the Pins/LGN/GPSM2-Dlg interaction and suggests new possibilities for its importance in spindle orientation during epithelial and neural tissue development.}, } @article {pmid34592312, year = {2021}, author = {Shrestha, S and Clark, AC}, title = {Evolution of the folding landscape of effector caspases.}, journal = {The Journal of biological chemistry}, volume = {297}, number = {5}, pages = {101249}, pmid = {34592312}, issn = {1083-351X}, support = {R01 GM127654/GM/NIGMS NIH HHS/United States ; }, mesh = {Caspases, Effector/*chemistry/genetics/metabolism ; *Evolution, Molecular ; Humans ; *Models, Molecular ; *Protein Folding ; *Protein Multimerization ; }, abstract = {Caspases are a family of cysteinyl proteases that control programmed cell death and maintain homeostasis in multicellular organisms. The caspase family is an excellent model to study protein evolution because all caspases are produced as zymogens (procaspases [PCPs]) that must be activated to gain full activity; the protein structures are conserved through hundreds of millions of years of evolution; and some allosteric features arose with the early ancestor, whereas others are more recent evolutionary events. The apoptotic caspases evolved from a common ancestor (CA) into two distinct subfamilies: monomers (initiator caspases) or dimers (effector caspases). Differences in activation mechanisms of the two subfamilies, and their oligomeric forms, play a central role in the regulation of apoptosis. Here, we examine changes in the folding landscape by characterizing human effector caspases and their CA. The results show that the effector caspases unfold by a minimum three-state equilibrium model at pH 7.5, where the native dimer is in equilibrium with a partially folded monomeric (PCP-7, CA) or dimeric (PCP-6) intermediate. In comparison, the unfolding pathway of PCP-3 contains both oligomeric forms of the intermediate. Overall, the data show that the folding landscape was first established with the CA and was retained for >650 million years. Partially folded monomeric or dimeric intermediates in the ancestral ensemble provide mechanisms for evolutionary changes that affect stability of extant caspases. The conserved folding landscape allows for the fine-tuning of enzyme stability in a species-dependent manner while retaining the overall caspase-hemoglobinase fold.}, } @article {pmid34592264, year = {2022}, author = {Sego, TJ and Mochan, ED and Ermentrout, GB and Glazier, JA}, title = {A multiscale multicellular spatiotemporal model of local influenza infection and immune response.}, journal = {Journal of theoretical biology}, volume = {532}, number = {}, pages = {110918}, pmid = {34592264}, issn = {1095-8541}, support = {U24 EB028887/EB/NIBIB NIH HHS/United States ; R01 GM122424/GM/NIGMS NIH HHS/United States ; }, mesh = {*COVID-19 ; Humans ; Immunity, Innate ; *Influenza, Human ; SARS-CoV-2 ; *Virus Diseases ; }, abstract = {Respiratory viral infections pose a serious public health concern, from mild seasonal influenza to pandemics like those of SARS-CoV-2. Spatiotemporal dynamics of viral infection impact nearly all aspects of the progression of a viral infection, like the dependence of viral replication rates on the type of cell and pathogen, the strength of the immune response and localization of infection. Mathematical modeling is often used to describe respiratory viral infections and the immune response to them using ordinary differential equation (ODE) models. However, ODE models neglect spatially-resolved biophysical mechanisms like lesion shape and the details of viral transport, and so cannot model spatial effects of a viral infection and immune response. In this work, we develop a multiscale, multicellular spatiotemporal model of influenza infection and immune response by combining non-spatial ODE modeling and spatial, cell-based modeling. We employ cellularization, a recently developed method for generating spatial, cell-based, stochastic models from non-spatial ODE models, to generate much of our model from a calibrated ODE model that describes infection, death and recovery of susceptible cells and innate and adaptive responses during influenza infection, and develop models of cell migration and other mechanisms not explicitly described by the ODE model. We determine new model parameters to generate agreement between the spatial and original ODE models under certain conditions, where simulation replicas using our model serve as microconfigurations of the ODE model, and compare results between the models to investigate the nature of viral exposure and impact of heterogeneous infection on the time-evolution of the viral infection. We found that using spatially homogeneous initial exposure conditions consistently with those employed during calibration of the ODE model generates far less severe infection, and that local exposure to virus must be multiple orders of magnitude greater than a uniformly applied exposure to all available susceptible cells. This strongly suggests a prominent role of localization of exposure in influenza A infection. We propose that the particularities of the microenvironment to which a virus is introduced plays a dominant role in disease onset and progression, and that spatially resolved models like ours may be important to better understand and more reliably predict future health states based on susceptibility of potential lesion sites using spatially resolved patient data of the state of an infection. We can readily integrate the immune response components of our model into other modeling and simulation frameworks of viral infection dynamics that do detailed modeling of other mechanisms like viral internalization and intracellular viral replication dynamics, which are not explicitly represented in the ODE model. We can also combine our model with available experimental data and modeling of exposure scenarios and spatiotemporal aspects of mechanisms like mucociliary clearance that are only implicitly described by the ODE model, which would significantly improve the ability of our model to present spatially resolved predictions about the progression of influenza infection and immune response.}, } @article {pmid34575761, year = {2021}, author = {Gostinčar, C and Stajich, JE and Kejžar, A and Sinha, S and Nislow, C and Lenassi, M and Gunde-Cimerman, N}, title = {Seven Years at High Salinity-Experimental Evolution of the Extremely Halotolerant Black Yeast Hortaea werneckii.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {7}, number = {9}, pages = {}, pmid = {34575761}, issn = {2309-608X}, support = {Infrastructural Centre Mycosmo (MRIC UL)//Javna Agencija za Raziskovalno Dejavnost RS/ ; P1-0170//Javna Agencija za Raziskovalno Dejavnost RS/ ; P1-0198//Javna Agencija za Raziskovalno Dejavnost RS/ ; J4-2549//Javna Agencija za Raziskovalno Dejavnost RS/ ; C.N.//Canada Research Chairs/ ; }, abstract = {The experimental evolution of microorganisms exposed to extreme conditions can provide insight into cellular adaptation to stress. Typically, stress-sensitive species are exposed to stress over many generations and then examined for improvements in their stress tolerance. In contrast, when starting with an already stress-tolerant progenitor there may be less room for further improvement, it may still be able to tweak its cellular machinery to increase extremotolerance, perhaps at the cost of poorer performance under non-extreme conditions. To investigate these possibilities, a strain of extremely halotolerant black yeast Hortaea werneckii was grown for over seven years through at least 800 generations in a medium containing 4.3 M NaCl. Although this salinity is well above the optimum (0.8-1.7 M) for the species, the growth rate of the evolved H. werneckii did not change in the absence of salt or at high concentrations of NaCl, KCl, sorbitol, or glycerol. Other phenotypic traits did change during the course of the experimental evolution, including fewer multicellular chains in the evolved strains, significantly narrower cells, increased resistance to caspofungin, and altered melanisation. Whole-genome sequencing revealed the occurrence of multiple aneuploidies during the experimental evolution of the otherwise diploid H. werneckii. A significant overrepresentation of several gene groups was observed in aneuploid regions. Taken together, these changes suggest that long-term growth at extreme salinity led to alterations in cell wall and morphology, signalling pathways, and the pentose phosphate cycle. Although there is currently limited evidence for the adaptive value of these changes, they offer promising starting points for future studies of fungal halotolerance.}, } @article {pmid34571874, year = {2021}, author = {Buravkova, L and Larina, I and Andreeva, E and Grigoriev, A}, title = {Microgravity Effects on the Matrisome.}, journal = {Cells}, volume = {10}, number = {9}, pages = {}, pmid = {34571874}, issn = {2073-4409}, support = {65.3//Program of Basic Research of IBMP RAS/ ; 19-29-04026//Russian Foundation for Fundamental Investigations/ ; }, mesh = {Animals ; Extracellular Matrix/*physiology ; Gravity, Altered ; Humans ; Space Flight/methods ; Weightlessness ; }, abstract = {Gravity is fundamental factor determining all processes of development and vital activity on Earth. During evolution, a complex mechanism of response to gravity alterations was formed in multicellular organisms. It includes the "gravisensors" in extracellular and intracellular spaces. Inside the cells, the cytoskeleton molecules are the principal gravity-sensitive structures, and outside the cells these are extracellular matrix (ECM) components. The cooperation between the intracellular and extracellular compartments is implemented through specialized protein structures, integrins. The gravity-sensitive complex is a kind of molecular hub that coordinates the functions of various tissues and organs in the gravitational environment. The functioning of this system is of particular importance under extremal conditions, such as spaceflight microgravity. This review covers the current understanding of ECM and associated molecules as the matrisome, the features of the above components in connective tissues, and the role of the latter in the cell and tissue responses to the gravity alterations. Special attention is paid to contemporary methodological approaches to the matrisome composition analysis under real space flights and ground-based simulation of its effects on Earth.}, } @article {pmid34571814, year = {2021}, author = {Reuveni, M}, title = {Sex and Regeneration.}, journal = {Biology}, volume = {10}, number = {9}, pages = {}, pmid = {34571814}, issn = {2079-7737}, abstract = {Regeneration is usually regarded as a unique plant or some animal species process. In reality, regeneration is a ubiquitous process in all multicellular organisms. It ranges from response to wounding by healing the wounded tissue to whole body neoforming (remaking of the new body). In a larger context, regeneration is one facet of two reproduction schemes that dominate the evolution of life. Multicellular organisms can propagate their genes asexually or sexually. Here I present the view that the ability to regenerate tissue or whole-body regeneration is also determined by the sexual state of the multicellular organisms (from simple animals such as hydra and planaria to plants and complex animals). The above idea is manifested here by showing evidence that many organisms, organs, or tissues show inhibited or diminished regeneration capacity when in reproductive status compared to organs or tissues in nonreproductive conditions or by exposure to sex hormones.}, } @article {pmid34567752, year = {2021}, author = {Qu, F and Zhao, S and Cheng, G and Rahman, H and Xiao, Q and Chan, RWY and Ho, YP}, title = {Double emulsion-pretreated microwell culture for the in vitro production of multicellular spheroids and their in situ analysis.}, journal = {Microsystems & nanoengineering}, volume = {7}, number = {}, pages = {38}, pmid = {34567752}, issn = {2055-7434}, abstract = {Multicellular spheroids have served as a promising preclinical model for drug efficacy testing and disease modeling. Many microfluidic technologies, including those based on water-oil-water double emulsions, have been introduced for the production of spheroids. However, sustained culture and the in situ characterization of the generated spheroids are currently unavailable for the double emulsion-based spheroid model. This study presents a streamlined workflow, termed the double emulsion-pretreated microwell culture (DEPMiC), incorporating the features of (1) effective initiation of uniform-sized multicellular spheroids by the pretreatment of double emulsions produced by microfluidics without the requirement of biomaterial scaffolds; (2) sustained maintenance and culture of the produced spheroids with facile removal of the oil confinement; and (3) in situ characterization of individual spheroids localized in microwells by a built-in analytical station. Characterized by microscopic observations and Raman spectroscopy, the DEPMiC cultivated spheroids accumulated elevated lipid ordering on the apical membrane, similar to that observed in their Matrigel counterparts. Made possible by the proposed technological advancement, this study subsequently examined the drug responses of these in vitro-generated multicellular spheroids. The developed DEPMiC platform is expected to generate health benefits in personalized cancer treatment by offering a pre-animal tool to dissect heterogeneity from individual tumor spheroids.}, } @article {pmid34564856, year = {2021}, author = {Charles Campbell, F}, title = {Untangling the complexities of micropapillary cancer[†].}, journal = {The Journal of pathology}, volume = {255}, number = {4}, pages = {343-345}, doi = {10.1002/path.5809}, pmid = {34564856}, issn = {1096-9896}, support = {C9136/A15342/CRUK_/Cancer Research UK/United Kingdom ; MR/L015110/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Adenocarcinoma of Lung ; *Carcinoma, Papillary ; Cell Polarity ; *Colorectal Neoplasms ; Humans ; *Lung Neoplasms ; }, abstract = {Distinct morphological subtypes of colorectal cancer (CRC) confer a bleak clinical outlook. In a recent issue of The Journal of Pathology, Onuma et al investigated morphological evolution of a highly fatal CRC subtype known as micropapillary cancer (MPC). This study enhances understanding of MPC biology including essential regulatory signals, cellular and multicellular phenotypes, as well as cancer behaviour. Iterative modelling in three-dimensional (3D) patient-derived CRC tissue-originated spheroids (CTOSs) revealed spatiotemporal oscillations of Rho-ROCK hyperactivity underlying reversal of membrane polarity and suppression of lumen formation during development of multicellular MPC morphology. Corroborative studies in CTOSs, xenografts, and archival human CRCs confirm human disease relevance. Although cancer morphology has previously been considered irreversible, targeted inhibition of Rho-ROCK activity restored membrane polarity, lumenized multicellular assembly, and suppressed MPC morphology in 3D CTOS cultures and xenografts. Collectively, the study identifies molecular, biophysical, and multicellular mechanisms implicated in morphological evolution of micropapillary CRC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.}, } @article {pmid34556094, year = {2021}, author = {Krishna, A and Gardiner, J and Donner, TJ and Scarpella, E}, title = {Control of vein-forming, striped gene expression by auxin signaling.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {213}, pmid = {34556094}, issn = {1741-7007}, mesh = {*Arabidopsis/genetics/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Gene Expression ; Gene Expression Regulation, Plant ; Indoleacetic Acids ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Activation of gene expression in striped domains is a key building block of biological patterning, from the recursive formation of veins in plant leaves to that of ribs and vertebrae in our bodies. In animals, gene expression is activated in striped domains by the differential affinity of broadly expressed transcription factors for their target genes and the combinatorial interaction between such target genes. In plants, how gene expression is activated in striped domains is instead unknown. We address this question for the broadly expressed MONOPTEROS (MP) transcription factor and its target gene ARABIDOPSIS THALIANA HOMEOBOX FACTOR8 (ATHB8).

RESULTS: We find that ATHB8 promotes vein formation and that such vein-forming function depends on both levels of ATHB8 expression and width of ATHB8 expression domains. We further find that ATHB8 expression is activated in striped domains by a combination of (1) activation of ATHB8 expression through binding of peak levels of MP to a low-affinity MP-binding site in the ATHB8 promoter and (2) repression of ATHB8 expression by MP target genes of the AUXIN/INDOLE-3-ACETIC-ACID-INDUCIBLE family.

CONCLUSIONS: Our findings suggest that a common regulatory logic controls activation of gene expression in striped domains in both plants and animals despite the independent evolution of their multicellularity.}, } @article {pmid34547424, year = {2021}, author = {Kun, Á}, title = {The major evolutionary transitions and codes of life.}, journal = {Bio Systems}, volume = {210}, number = {}, pages = {104548}, doi = {10.1016/j.biosystems.2021.104548}, pmid = {34547424}, issn = {1872-8324}, mesh = {Animals ; *Biological Evolution ; Genetic Code/*genetics ; Humans ; Organelles/*physiology ; *Origin of Life ; Spheroids, Cellular/physiology ; }, abstract = {Major evolutionary transitions as well as the evolution of codes of life are key elements in macroevolution which are characterized by increase in complexity Major evolutionary transitions ensues by a transition in individuality and by the evolution of a novel mode of using, transmitting or storing information. Here is where codes of life enter the picture: they are arbitrary mappings between different (mostly) molecular species. This flexibility allows information to be employed in a variety of ways, which can fuel evolutionary innovation. The collation of the list of major evolutionary transitions and the list of codes of life show a clear pattern: codes evolved prior to a major evolutionary transition and then played roles in the transition and/or in the transformation of the new individual. The evolution of a new code of life is in itself not a major evolutionary transition but allow major evolutionary transitions to happen. This could help us to identify new organic codes.}, } @article {pmid34546795, year = {2021}, author = {Umen, J and Herron, MD}, title = {Green Algal Models for Multicellularity.}, journal = {Annual review of genetics}, volume = {55}, number = {}, pages = {603-632}, doi = {10.1146/annurev-genet-032321-091533}, pmid = {34546795}, issn = {1545-2948}, support = {R01 GM126557/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; *Chlorophyta/genetics ; Genome ; Phylogeny ; *Volvox/genetics ; }, abstract = {The repeated evolution of multicellularity across the tree of life has profoundly affected the ecology and evolution of nearly all life on Earth. Many of these origins were in different groups of photosynthetic eukaryotes, or algae. Here, we review the evolution and genetics of multicellularity in several groups of green algae, which include the closest relatives of land plants. These include millimeter-scale, motile spheroids of up to 50,000 cells in the volvocine algae; decimeter-scale seaweeds in the genus Ulva (sea lettuce); and very plantlike, meter-scale freshwater algae in the genus Chara (stoneworts). We also describe algae in the genus Caulerpa, which are giant, multinucleate, morphologically complex single cells. In each case, we review the life cycle, phylogeny, and genetics of traits relevant to the evolution of multicellularity, and genetic and genomic resources available for the group in question. Finally, we suggest routes toward developing these groups as model organisms for the evolution of multicellularity.}, } @article {pmid34545570, year = {2021}, author = {Maryenti, T and Ishii, T and Okamoto, T}, title = {Development and regeneration of wheat-rice hybrid zygotes produced by in vitro fertilization system.}, journal = {The New phytologist}, volume = {232}, number = {6}, pages = {2369-2383}, pmid = {34545570}, issn = {1469-8137}, mesh = {Fertilization in Vitro ; *Oryza/genetics ; Seeds/genetics ; Triticum/genetics ; *Zygote ; }, abstract = {Hybridization plays a decisive role in the evolution and diversification of angiosperms. However, the mechanisms of wide hybridization remain open because pre- and post-fertilization barriers limit the production and development of inter-subfamily/intergeneric zygotes, respectively. We examined hybridization between wheat and rice using an in vitro fertilization (IVF) system to bypass these barriers. Several gamete combinations of allopolyploid wheat-rice hybrid zygotes were successfully produced, and the developmental profiles of hybrid zygotes were analyzed. Hybrid zygotes derived from one rice egg cell and one wheat sperm cell ceased at the multicellular embryo-like structure stage. This developmental barrier was overcome by adding one wheat egg cell to the wheat-rice hybrid zygote. In the reciprocal combination, one wheat egg and one rice sperm cell, the resulting hybrid zygotes failed to divide. However, doubling the dosage of rice sperm cell allowed the hybrid zygotes to develop into plantlets. Rice chromosomes appeared to be progressively eliminated during the early developmental stage of these hybrid embryos, and c. 20% of regenerated plants showed abnormal morphology. These results suggest that hybrid breakdown can be overcome through optimization of gamete combinations, and the present hybrid will provide a new horizon for utilization of inter-subfamily genetic resources.}, } @article {pmid34529755, year = {2021}, author = {Turney, PD}, title = {Evolution of Autopoiesis and Multicellularity in the Game of Life.}, journal = {Artificial life}, volume = {27}, number = {1}, pages = {26-43}, doi = {10.1162/artl_a_00334}, pmid = {34529755}, issn = {1530-9185}, mesh = {Biological Evolution ; Models, Biological ; *Reproduction ; *Selection, Genetic ; Symbiosis ; }, abstract = {Recently we introduced a model of symbiosis, Model-S, based on the evolution of seed patterns in Conway's Game of Life. In the model, the fitness of a seed pattern is measured by one-on-one competitions in the Immigration Game, a two-player variation of the Game of Life. Our previous article showed that Model-S can serve as a highly abstract, simplified model of biological life: (1) The initial seed pattern is analogous to a genome. (2) The changes as the game runs are analogous to the development of the phenome. (3) Tournament selection in Model-S is analogous to natural selection in biology. (4) The Immigration Game in Model-S is analogous to competition in biology. (5) The first three layers in Model-S are analogous to biological reproduction. (6) The fusion of seed patterns in Model-S is analogous to symbiosis. The current article takes this analogy two steps further: (7) Autopoietic structures in the Game of Life (still lifes, oscillators, and spaceships-collectively known as ashes) are analogous to cells in biology. (8) The seed patterns in the Game of Life give rise to multiple, diverse, cooperating autopoietic structures, analogous to multicellular biological life. We use the apgsearch software (Ash Pattern Generator Search), developed by Adam Goucher for the study of ashes, to analyze autopoiesis and multicellularity in Model-S. We find that the fitness of evolved seed patterns in Model-S is highly correlated with the diversity and quantity of multicellular autopoietic structures.}, } @article {pmid34529461, year = {2021}, author = {Leslie, AB and Simpson, C and Mander, L}, title = {Reproductive innovations and pulsed rise in plant complexity.}, journal = {Science (New York, N.Y.)}, volume = {373}, number = {6561}, pages = {1368-1372}, doi = {10.1126/science.abi6984}, pmid = {34529461}, issn = {1095-9203}, mesh = {*Biological Evolution ; Cycadopsida/anatomy & histology/genetics/growth & development ; Embryophyta/*anatomy & histology/growth & development/physiology ; Flowers/*anatomy & histology ; Fossils ; Magnoliopsida/anatomy & histology/genetics/growth & development/physiology ; Plant Structures/*anatomy & histology/growth & development ; Pollination ; Reproduction ; *Seeds ; Sporangia/anatomy & histology ; }, abstract = {Morphological complexity is a notable feature of multicellular life, although whether it evolves gradually or in early bursts is unclear. Vascular plant reproductive structures, such as flowers, are familiar examples of complex morphology. In this study, we use a simple approach based on the number of part types to analyze changes in complexity over time. We find that reproductive complexity increased in two pulses separated by ~250 million years of stasis, including an initial rise in the Devonian with the radiation of vascular plants and a pronounced increase in the Late Cretaceous that reflects flowering plant diversification. These pulses are associated with innovations that increased functional diversity, suggesting that shifts in complexity are linked to changes in function regardless of whether they occur early or late in the history of vascular plants.}, } @article {pmid34525330, year = {2021}, author = {Martinez-Miguel, VE and Lujan, C and Espie-Caullet, T and Martinez-Martinez, D and Moore, S and Backes, C and Gonzalez, S and Galimov, ER and Brown, AEX and Halic, M and Tomita, K and Rallis, C and von der Haar, T and Cabreiro, F and Bjedov, I}, title = {Increased fidelity of protein synthesis extends lifespan.}, journal = {Cell metabolism}, volume = {33}, number = {11}, pages = {2288-2300.e12}, pmid = {34525330}, issn = {1932-7420}, support = {R01 GM135599/GM/NIGMS NIH HHS/United States ; C416/A25145/CRUK_/Cancer Research UK/United Kingdom ; C7893/A28990/CRUK_/Cancer Research UK/United Kingdom ; MC_UP_1102/6/MRC_/Medical Research Council/United Kingdom ; MC_UP_1605/6/MRC_/Medical Research Council/United Kingdom ; 201487/WT_/Wellcome Trust/United Kingdom ; 102532/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; BB/V006916/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 102531/Z/13/A/WT_/Wellcome Trust/United Kingdom ; MR/M02492X/1/MRC_/Medical Research Council/United Kingdom ; MC-A654-5QC80/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Longevity/genetics ; Phylogeny ; Protein Biosynthesis ; *Proteostasis/genetics ; Saccharomyces cerevisiae/genetics ; }, abstract = {Loss of proteostasis is a fundamental process driving aging. Proteostasis is affected by the accuracy of translation, yet the physiological consequence of having fewer protein synthesis errors during multi-cellular organismal aging is poorly understood. Our phylogenetic analysis of RPS23, a key protein in the ribosomal decoding center, uncovered a lysine residue almost universally conserved across all domains of life, which is replaced by an arginine in a small number of hyperthermophilic archaea. When introduced into eukaryotic RPS23 homologs, this mutation leads to accurate translation, as well as heat shock resistance and longer life, in yeast, worms, and flies. Furthermore, we show that anti-aging drugs such as rapamycin, Torin1, and trametinib reduce translation errors, and that rapamycin extends further organismal longevity in RPS23 hyperaccuracy mutants. This implies a unified mode of action for diverse pharmacological anti-aging therapies. These findings pave the way for identifying novel translation accuracy interventions to improve aging.}, } @article {pmid34524972, year = {2021}, author = {Gajdács, M and Kárpáti, K and Nagy, ÁL and Gugolya, M and Stájer, A and Burián, K}, title = {Association between biofilm-production and antibiotic resistance in Escherichia coli isolates: A laboratory-based case study and a literature review.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {}, number = {}, pages = {}, doi = {10.1556/030.2021.01487}, pmid = {34524972}, issn = {1588-2640}, abstract = {Bacteria can enhance their survival by attaching to inanimate surfaces or tissues, and presenting as multicellular communities encased in a protective extracellular matrix called biofilm. There has been pronounced interest in assessing the relationship between the antibiotic resistant phenotype and biofilm-production in clinically-relevant pathogens. The aim of the present paper was to provide additional experimental results on the topic, testing the biofilm-forming capacity of Escherichia coli isolates using in vitro methods in the context of their antibiotic resistance in the form of a laboratory case study, in addition to provide a comprehensive review of the subject. In our case study, a total of two hundred and fifty (n = 250) E. coli isolates, originating from either clean-catch urine samples (n = 125) or invasive samples (n = 125) were included. The colony morphology of isolates were recorded after 24h, while antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Biofilm-formation of the isolates was assessed with the crystal violet tube-adherence method. Altogether 57 isolates (22.8%) isolates were multidrug resistant (MDR), 89 isolates (35.6%) produced large colonies (>3 mm), mucoid variant colonies were produced in 131 cases (52.4%), and 108 (43.2%) were positive for biofilm formation. Biofilm-producers were less common among isolates resistant to third-generation cephalosporins and trimethoprim-sulfamethoxazole (P = 0.043 and P = 0.023, respectively). Biofilms facilitate a protective growth strategy in bacteria, ensuring safety against environmental stressors, components of the immune system and noxious chemical agents. Being an integral part of bacterial physiology, biofilm-formation is interdependent with the expression of other virulence factors (especially adhesins) and quorum sensing signal molecules. More research is required to allow for the full understanding of the interplay between the MDR phenotype and biofilm-production, which will facilitate the development of novel therapeutic strategies.}, } @article {pmid34521896, year = {2021}, author = {Elsner, D and Hartfelder, K and Korb, J}, title = {Molecular underpinnings of division of labour among workers in a socially complex termite.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {18269}, pmid = {34521896}, issn = {2045-2322}, mesh = {Animals ; Biological Evolution ; *Evolution, Molecular ; Female ; Gene Expression ; Gene Expression Profiling ; Genes, Insect/genetics ; Isoptera/*genetics/physiology ; Male ; *Social Behavior ; Transcriptome/genetics ; }, abstract = {Division of labour characterizes all major evolutionary transitions, such as the evolution of eukaryotic cells or multicellular organisms. Social insects are characterized by reproductive division of labour, with one or a few reproducing individuals (queens) and many non-reproducing nestmates (workers) forming a colony. Among the workers, further division of labour can occur with different individuals performing different tasks such as foraging, brood care or building. While mechanisms underlying task division are intensively studied in social Hymenoptera, less is known for termites, which independently evolved eusociality. We investigated molecular mechanisms underlying task division in termite workers to test for communality with social Hymenoptera. We compared similar-aged foraging workers with builders of the fungus-growing termite Macrotermes bellicosus using transcriptomes, endocrine measures and estimators of physiological condition. Based on results for social Hymenoptera and theory, we tested the hypotheses that (i) foragers are in worse physiological conditions than builders, (ii) builders are more similar in their gene expression profile to queens than foragers are, and (iii) builders invest more in anti-ageing mechanism than foragers. Our results support all three hypotheses. We found storage proteins to underlie task division of these similar-aged termite workers and these genes also characterize reproductive division of labour between queens and workers. This implies a co-option of nutrient-based pathways to regulate division of labour across lineages of termites and social Hymenoptera, which are separated by more than 133 million years.}, } @article {pmid34520764, year = {2021}, author = {Steventon, B and Busby, L and Arias, AM}, title = {Establishment of the vertebrate body plan: Rethinking gastrulation through stem cell models of early embryogenesis.}, journal = {Developmental cell}, volume = {56}, number = {17}, pages = {2405-2418}, doi = {10.1016/j.devcel.2021.08.012}, pmid = {34520764}, issn = {1878-1551}, support = {109408/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Embryonic Development/genetics/*physiology ; Gastrulation/*physiology ; Gene Expression Regulation, Developmental/genetics/physiology ; Humans ; Morphogenesis/*physiology ; Stem Cells/*cytology ; Vertebrates/genetics ; }, abstract = {A striking property of vertebrate embryos is the emergence of a conserved body plan across a wide range of organisms through the process of gastrulation. As the body plan unfolds, gene regulatory networks (GRNs) and multicellular interactions (cell regulatory networks, CRNs) combine to generate a conserved set of morphogenetic events that lead to the phylotypic stage. Interrogation of these multilevel interactions requires manipulation of the mechanical environment, which is difficult in vivo. We review recent studies of stem cell models of early embryogenesis from different species showing that, independent of species origin, cells in culture form similar structures. The main difference between embryos and in vitro models is the boundary conditions of the multicellular ensembles. We discuss these observations and suggest that the mechanical and geometric boundary conditions of different embryos before gastrulation hide a morphogenetic ground state that is revealed in the stem-cell-based models of embryo development.}, } @article {pmid34516543, year = {2021}, author = {Henriques, GJB and van Vliet, S and Doebeli, M}, title = {Multilevel selection favors fragmentation modes that maintain cooperative interactions in multispecies communities.}, journal = {PLoS computational biology}, volume = {17}, number = {9}, pages = {e1008896}, pmid = {34516543}, issn = {1553-7358}, mesh = {*Models, Biological ; Mutation ; Plants/classification/genetics ; Reproduction/genetics ; *Selection, Genetic ; Species Specificity ; }, abstract = {Reproduction is one of the requirements for evolution and a defining feature of life. Yet, across the tree of life, organisms reproduce in many different ways. Groups of cells (e.g., multicellular organisms, colonial microbes, or multispecies biofilms) divide by releasing propagules that can be single-celled or multicellular. What conditions determine the number and size of reproductive propagules? In multicellular organisms, existing theory suggests that single-cell propagules prevent the accumulation of deleterious mutations (e.g., cheaters). However, groups of cells, such as biofilms, sometimes contain multiple metabolically interdependent species. This creates a reproductive dilemma: small daughter groups, which prevent the accumulation of cheaters, are also unlikely to contain the species diversity that is required for ecological success. Here, we developed an individual-based, multilevel selection model to investigate how such multi-species groups can resolve this dilemma. By tracking the dynamics of groups of cells that reproduce by fragmenting into smaller groups, we identified fragmentation modes that can maintain cooperative interactions. We systematically varied the fragmentation mode and calculated the maximum mutation rate that communities can withstand before being driven to extinction by the accumulation of cheaters. We find that for groups consisting of a single species, the optimal fragmentation mode consists of releasing single-cell propagules. For multi-species groups we find various optimal strategies. With migration between groups, single-cell propagules are favored. Without migration, larger propagules sizes are optimal; in this case, group-size dependent fissioning rates can prevent the accumulation of cheaters. Our work shows that multi-species groups can evolve reproductive strategies that allow them to maintain cooperative interactions.}, } @article {pmid34515793, year = {2021}, author = {Yeung, W and Kwon, A and Taujale, R and Bunn, C and Venkat, A and Kannan, N}, title = {Evolution of Functional Diversity in the Holozoan Tyrosine Kinome.}, journal = {Molecular biology and evolution}, volume = {38}, number = {12}, pages = {5625-5639}, pmid = {34515793}, issn = {1537-1719}, support = {R01 GM114409/GM/NIGMS NIH HHS/United States ; R35 GM139656/GM/NIGMS NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; Phosphorylation ; Phylogeny ; *Protein-Tyrosine Kinases/genetics/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/metabolism ; Signal Transduction ; *Tyrosine/metabolism ; }, abstract = {The emergence of multicellularity is strongly correlated with the expansion of tyrosine kinases, a conserved family of signaling enzymes that regulates pathways essential for cell-to-cell communication. Although tyrosine kinases have been classified from several model organisms, a molecular-level understanding of tyrosine kinase evolution across all holozoans is currently lacking. Using a hierarchical sequence constraint-based classification of diverse holozoan tyrosine kinases, we construct a new phylogenetic tree that identifies two ancient clades of cytoplasmic and receptor tyrosine kinases separated by the presence of an extended insert segment in the kinase domain connecting the D and E-helices. Present in nearly all receptor tyrosine kinases, this fast-evolving insertion imparts diverse functionalities, such as post-translational modification sites and regulatory interactions. Eph and EGFR receptor tyrosine kinases are two exceptions which lack this insert, each forming an independent lineage characterized by unique functional features. We also identify common constraints shared across multiple tyrosine kinase families which warrant the designation of three new subgroups: Src module (SrcM), insulin receptor kinase-like (IRKL), and fibroblast, platelet-derived, vascular, and growth factor receptors (FPVR). Subgroup-specific constraints reflect shared autoinhibitory interactions involved in kinase conformational regulation. Conservation analyses describe how diverse tyrosine kinase signaling functions arose through the addition of family-specific motifs upon subgroup-specific features and coevolving protein domains. We propose the oldest tyrosine kinases, IRKL, SrcM, and Csk, originated from unicellular premetazoans and were coopted for complex multicellular functions. The increased frequency of oncogenic variants in more recent tyrosine kinases suggests that lineage-specific functionalities are selectively altered in human cancers.}, } @article {pmid34512720, year = {2021}, author = {Lemoine, M}, title = {The Evolution of the Hallmarks of Aging.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {693071}, pmid = {34512720}, issn = {1664-8021}, abstract = {The evolutionary theory of aging has set the foundations for a comprehensive understanding of aging. The biology of aging has listed and described the "hallmarks of aging," i.e., cellular and molecular mechanisms involved in human aging. The present paper is the first to infer the order of appearance of the hallmarks of bilaterian and thereby human aging throughout evolution from their presence in progressively narrower clades. Its first result is that all organisms, even non-senescent, have to deal with at least one mechanism of aging - the progressive accumulation of misfolded or unstable proteins. Due to their cumulation, these mechanisms are called "layers of aging." A difference should be made between the first four layers of unicellular aging, present in some unicellular organisms and in all multicellular opisthokonts, that stem and strike "from the inside" of individual cells and span from increasingly abnormal protein folding to deregulated nutrient sensing, and the last four layers of metacellular aging, progressively appearing in metazoans, that strike the cells of a multicellular organism "from the outside," i.e., because of other cells, and span from transcriptional alterations to the disruption of intercellular communication. The evolution of metazoans and eumetazoans probably solved the problem of aging along with the problem of unicellular aging. However, metacellular aging originates in the mechanisms by which the effects of unicellular aging are kept under control - e.g., the exhaustion of stem cells that contribute to replace damaged somatic cells. In bilaterians, additional functions have taken a toll on generally useless potentially limited lifespan to increase the fitness of organisms at the price of a progressively less efficient containment of the damage of unicellular aging. In the end, this picture suggests that geroscience should be more efficient in targeting conditions of metacellular aging rather than unicellular aging itself.}, } @article {pmid34486115, year = {2021}, author = {Roy, SW}, title = {Digest: Three sexes from two loci in one genome: A haploid alga expands the diversity of trioecious species.}, journal = {Evolution; international journal of organic evolution}, volume = {75}, number = {11}, pages = {3002-3003}, doi = {10.1111/evo.14345}, pmid = {34486115}, issn = {1558-5646}, mesh = {Female ; *Genome ; Haploidy ; Humans ; Male ; }, abstract = {Multicellular eukaryotes exhibit a remarkable diversity of sexual systems; however, trioecy, the coexistence of male, female, and cosexual or hermaphrodite individuals in a single species, is remarkably rare. Takahashi et al. (2021) report the first known instance of trioecy in a haploid organism. In contrast to other known cases of trioecy, the authors report evidence for genetic control of all three sexes by two loci. These results complicate models for sexual system turnover and expand the known diversity of trioecy species in several ways.}, } @article {pmid34485312, year = {2021}, author = {Gómez, DP and Boudreau, F}, title = {Organoids and Their Use in Modeling Gut Epithelial Cell Lineage Differentiation and Barrier Properties During Intestinal Diseases.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {732137}, pmid = {34485312}, issn = {2296-634X}, abstract = {Maintenance of intestinal epithelium homeostasis is a complex process because of the multicellular and molecular composition of the gastrointestinal wall and the involvement of surrounding interactive signals. The complex nature of this intestinal barrier system poses challenges in the detailed mechanistic understanding of intestinal morphogenesis and the onset of several gut pathologies, including intestinal inflammatory disorders, food allergies, and cancer. For several years, the gut scientific community has explored different alternatives in research involving animals and in vitro models consisting of cultured monolayers derived from the immortalized or cancerous origin cell lines. The recent ability to recapitulate intestinal epithelial dynamics from mini-gut cultures has proven to be a promising step in the field of scientific research and biomedicine. The organoids can be grown as two- or three-dimensional structures, and are derived from adult or pluripotent stem cells that ultimately establish an intestinal epithelium that is composed of all differentiated cell types present in the normal epithelium. In this review, we summarize the different origins and recent use of organoids in modeling intestinal epithelial differentiation and barrier properties.}, } @article {pmid34483853, year = {2021}, author = {Marshall, PJ and Houser, TM and Weiss, SM}, title = {The Shared Origins of Embodiment and Development.}, journal = {Frontiers in systems neuroscience}, volume = {15}, number = {}, pages = {726403}, pmid = {34483853}, issn = {1662-5137}, abstract = {As a domain of study centering on the nature of the body in the functioning of the individual organism, embodiment encompasses a diverse array of topics and questions. One useful organizing framework places embodiment as a bridge construct connecting three standpoints on the body: the form of the body, the body as actively engaged in and with the world, and the body as lived experience. Through connecting these standpoints, the construct of embodiment shows that they are not mutually exclusive: inherent in form is the capacity for engagement, and inherent in engagement is a lived perspective that confers agency and meaning. Here, we employ this framework to underscore the deep connections between embodiment and development. We begin with a discussion of the origins of multicellularity, highlighting how the evolution of bodies was the evolution of development itself. The evolution of the metazoan (animal) body is of particular interest, because most animals possess complex bodies with sensorimotor capacities for perceiving and acting that bring forth a particular sort of embodiment. However, we also emphasize that the thread of embodiment runs through all living things, which share an organizational property of self-determination that endows them with a specific kind of autonomy. This realization moves us away from a Cartesian machine metaphor and instead puts an emphasis on the lived perspective that arises from being embodied. This broad view of embodiment presents opportunities to transcend the boundaries of individual disciplines to create a novel integrative vision for the scientific study of development.}, } @article {pmid34480926, year = {2021}, author = {Mani, S and Tlusty, T}, title = {A topological look into the evolution of developmental programs.}, journal = {Biophysical journal}, volume = {120}, number = {19}, pages = {4193-4201}, pmid = {34480926}, issn = {1542-0086}, mesh = {*Biological Evolution ; *Selection, Genetic ; }, abstract = {Rapid advance of experimental techniques provides an unprecedented in-depth view into complex developmental processes. Still, little is known on how the complexity of multicellular organisms evolved by elaborating developmental programs and inventing new cell types. A hurdle to understanding developmental evolution is the difficulty of even describing the intertwined network of spatiotemporal processes underlying the development of complex multicellular organisms. Nonetheless, an overview of developmental trajectories can be obtained from cell type lineage maps. Here, we propose that these lineage maps can also reveal how developmental programs evolve: the modes of evolving new cell types in an organism should be visible in its developmental trajectories and therefore in the geometry of its cell type lineage map. This idea is demonstrated using a parsimonious generative model of developmental programs, which allows us to reliably survey the universe of all possible programs and examine their topological features. We find that, contrary to belief, tree-like lineage maps are rare, and lineage maps of complex multicellular organisms are likely to be directed acyclic graphs in which multiple developmental routes can converge on the same cell type. Although cell type evolution prescribes what developmental programs come into existence, natural selection prunes those programs that produce low-functioning organisms. Our model indicates that additionally, lineage map topologies are correlated with such a functional property: the ability of organisms to regenerate.}, } @article {pmid34477897, year = {2021}, author = {Swiatczak, B}, title = {Struggle within: evolution and ecology of somatic cell populations.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {78}, number = {21-22}, pages = {6797-6806}, pmid = {34477897}, issn = {1420-9071}, mesh = {Adaptive Immunity/genetics ; Animals ; Biological Evolution ; DNA/genetics ; Ecology ; Humans ; Mutation/*genetics ; Selection, Genetic/genetics ; }, abstract = {The extent to which normal (nonmalignant) cells of the body can evolve through mutation and selection during the lifetime of the organism has been a major unresolved issue in evolutionary and developmental studies. On the one hand, stable multicellular individuality seems to depend on genetic homogeneity and suppression of evolutionary conflicts at the cellular level. On the other hand, the example of clonal selection of lymphocytes indicates that certain forms of somatic mutation and selection are concordant with the organism-level fitness. Recent DNA sequencing and tissue physiology studies suggest that in addition to adaptive immune cells also neurons, epithelial cells, epidermal cells, hematopoietic stem cells and functional cells in solid bodily organs are subject to evolutionary forces during the lifetime of an organism. Here we refer to these recent studies and suggest that the expanding list of somatically evolving cells modifies idealized views of biological individuals as radically different from collectives.}, } @article {pmid34476388, year = {2021}, author = {Boedicker, JQ and Gangan, M and Naughton, K and Zhao, F and Gralnick, JA and El-Naggar, MY}, title = {Engineering Biological Electron Transfer and Redox Pathways for Nanoparticle Synthesis.}, journal = {Bioelectricity}, volume = {3}, number = {2}, pages = {126-135}, pmid = {34476388}, issn = {2576-3113}, abstract = {Many species of bacteria are naturally capable of types of electron transport not observed in eukaryotic cells. Some species live in environments containing heavy metals not typically encountered by cells of multicellular organisms, such as arsenic, cadmium, and mercury, leading to the evolution of enzymes to deal with these environmental toxins. Bacteria also inhabit a variety of extreme environments, and are capable of respiration even in the absence of oxygen as a terminal electron acceptor. Over the years, several of these exotic redox and electron transport pathways have been discovered and characterized in molecular-level detail, and more recently synthetic biology has begun to utilize these pathways to engineer cells capable of detecting and processing a variety of metals and semimetals. One such application is the biologically controlled synthesis of nanoparticles. This review will introduce the basic concepts of bacterial metal reduction, summarize recent work in engineering bacteria for nanoparticle production, and highlight the most cutting-edge work in the characterization and application of bacterial electron transport pathways.}, } @article {pmid34467433, year = {2021}, author = {Wang, X and Dong, F and Liu, J and Tan, Y and Hu, S and Zhao, H}, title = {The self-healing of Bacillus subtilis biofilms.}, journal = {Archives of microbiology}, volume = {203}, number = {9}, pages = {5635-5645}, pmid = {34467433}, issn = {1432-072X}, support = {11772047//National Natural Science Foundation of China/ ; 11972074//National Natural Science Foundation of China/ ; 11620101001//National Natural Science Foundation of China/ ; }, mesh = {*Bacillus subtilis ; *Biofilms ; Humans ; }, abstract = {Self-healing is an intrinsic ability that exists widely in every multicellular biological organism. Our recent experiments have shown that bacterial biofilms also have the ability to self-heal after man-make cuts, but the mechanism of biofilm self-healing have not been studied. We find that the healing process of cuts on the biofilm depends on cut geometries like its location or direction, the biofilm itself like the biofilm age, the growing substrate properties like its hardness, and also the environments such as the competitive growth of multiple biofilms. What is more, the healing rate along the cut is heterogeneous, and the maximum healing rate can reach 260 μm/h, which is three times the undestroyed biofilm expansion rate. The cut does not change the rounded shape growth of biofilms. Further study of phenotypic evolution shows that the cut delays bacterial differentiation; motile cells perceive the cut and move to the cut area, while the cut only heals when there are enough matrix-producing cells in the cut area. Our work suggests new ideas for developing self-healing materials.}, } @article {pmid34465312, year = {2021}, author = {Lindsey, CR and Rosenzweig, F and Herron, MD}, title = {Phylotranscriptomics points to multiple independent origins of multicellularity and cellular differentiation in the volvocine algae.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {182}, pmid = {34465312}, issn = {1741-7007}, mesh = {Bayes Theorem ; Biological Evolution ; Cell Differentiation ; Chlamydomonas reinhardtii ; *Phylogeny ; Transcriptome ; Volvox/genetics ; }, abstract = {BACKGROUND: The volvocine algae, which include the single-celled species Chlamydomonas reinhardtii and the colonial species Volvox carteri, serve as a model in which to study the evolution of multicellularity and cellular differentiation. Studies reconstructing the history of this group have by and large relied on datasets of one to a few genes for phylogenetic inference and ancestral character state reconstruction. As a result, volvocine phylogenies lack concordance depending on the number and/or type of genes (i.e., chloroplast vs nuclear) chosen for phylogenetic inference. While multiple studies suggest that multicellularity evolved only once in the volvocine algae, that each of its three colonial families is monophyletic, and that there have been at least three independent origins of cellular differentiation in the group, other studies call into question one or more of these conclusions. An accurate assessment of the evolutionary history of the volvocine algae requires inference of a more robust phylogeny.

RESULTS: We performed RNA sequencing (RNA-seq) on 55 strains representing 47 volvocine algal species and obtained similar data from curated databases on 13 additional strains. We then compiled a dataset consisting of transcripts for 40 single-copy, protein-coding, nuclear genes and subjected the predicted amino acid sequences of these genes to maximum likelihood, Bayesian inference, and coalescent-based analyses. These analyses show that multicellularity independently evolved at least twice in the volvocine algae and that the colonial family Goniaceae is not monophyletic. Our data further indicate that cellular differentiation arose independently at least four, and possibly as many as six times, within the volvocine algae.

CONCLUSIONS: Altogether, our results demonstrate that multicellularity and cellular differentiation are evolutionarily labile in the volvocine algae, affirming the importance of this group as a model system for the study of major transitions in the history of life.}, } @article {pmid34463760, year = {2021}, author = {Diegmiller, R and Doherty, CA and Stern, T and Imran Alsous, J and Shvartsman, SY}, title = {Size scaling in collective cell growth.}, journal = {Development (Cambridge, England)}, volume = {148}, number = {18}, pages = {}, pmid = {34463760}, issn = {1477-9129}, support = {R01 GM134204/GM/NIGMS NIH HHS/United States ; F31 HD098835/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Cell Proliferation/*physiology ; Developmental Biology/methods ; Diptera/physiology ; Germ Cells/physiology ; Oogenesis/physiology ; Organelles/physiology ; }, abstract = {Size is a fundamental feature of living entities and is intimately tied to their function. Scaling laws, which can be traced to D'Arcy Thompson and Julian Huxley, have emerged as a powerful tool for studying regulation of the growth dynamics of organisms and their constituent parts. Yet, throughout the 20th century, as scaling laws were established for single cells, quantitative studies of the coordinated growth of multicellular structures have lagged, largely owing to technical challenges associated with imaging and image processing. Here, we present a supervised learning approach for quantifying the growth dynamics of germline cysts during oogenesis. Our analysis uncovers growth patterns induced by the groupwise developmental dynamics among connected cells, and differential growth rates of their organelles. We also identify inter-organelle volumetric scaling laws, finding that nurse cell growth is linear over several orders of magnitude. Our approach leverages the ever-increasing quantity and quality of imaging data, and is readily amenable for studies of collective cell growth in other developmental contexts, including early mammalian embryogenesis and germline development.}, } @article {pmid34462837, year = {2021}, author = {Mikhalevich, VI}, title = {Aromorphoses in the Evolution of Unicellular Eukaryotes (as Exemplified by Foraminifera D'orbigny, 1826).}, journal = {Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections}, volume = {499}, number = {1}, pages = {105-108}, pmid = {34462837}, issn = {1608-3105}, mesh = {Eukaryota ; *Foraminifera/genetics ; }, abstract = {Aromorphoses of unicellular organisms are almost unexplored. Foraminifera provide a unique opportunity of such studies, having the most complex structure and being most fully represented in the geological record. In their development, more than 10 aromorphoses (key advances) have first been discovered, which arose in different classes of Foraminifera independently and in parallel. Of these, the key ones are the emergence of an agglutinated and then secreted calcareous shell, a bifontinal (bilamellar) wall, multichamberedness, differentiation of chambers, an integrating system of channels and nuclear dualism. They represent peculiar ways of evolution at the unicellular level. Multicameredness can be compared with multicellularity; differentiation of chambers, with differentiation of tissues; a system of channels, striking in its complexity and carrying O2, with the Metazoa circulatory system.}, } @article {pmid34458231, year = {2021}, author = {Pellissier, L and Koval, A and Marcourt, L and Ferreira Queiroz, E and Lecoultre, N and Leoni, S and Quiros-Guerrero, LM and Barthélémy, M and Duivelshof, BL and Guillarme, D and Tardy, S and Eparvier, V and Perron, K and Chave, J and Stien, D and Gindro, K and Katanaev, V and Wolfender, JL}, title = {Isolation and Identification of Isocoumarin Derivatives With Specific Inhibitory Activity Against Wnt Pathway and Metabolome Characterization of Lasiodiplodia venezuelensis.}, journal = {Frontiers in chemistry}, volume = {9}, number = {}, pages = {664489}, pmid = {34458231}, issn = {2296-2646}, abstract = {The Wnt signaling pathway controls multiple events during embryonic development of multicellular animals and is carcinogenic when aberrantly activated in adults. Breast cancers are dependent on Wnt pathway overactivation mostly through dysregulation of pathway component protein expression, which necessitates the search for therapeutically relevant compounds targeting them. Highly diverse microorganisms as endophytes represent an underexplored field in the therapeutic natural products research. In the present work, the objective was to explore the chemical diversity and presence of selective Wnt inhibitors within a unique collection of fungi isolated as foliar endophytes from the long-lived tropical palm Astrocaryum sciophilum. The fungi were cultured, extracted with ethyl acetate, and screened for their effects on the Wnt pathway and cell proliferation. The endophytic strain Lasiodiplodia venezuelensis was prioritized for scaled-up fractionation based on its selective activity. Application of geometric transfer from analytical HPLC conditions to semi-preparative scale and use of dry load sample introduction enabled the isolation of 15 pure compounds in a single step. Among the molecules identified, five are original natural products described for the first time, and six are new to this species. An active fraction obtained by semi-preparative HPLC was re-purified by UHPLC-PDA using a 1.7 µm phenyl column. 75 injections of 8 µg were necessary to obtain sufficient amounts of each compound for structure elucidation and bioassays. Using this original approach, in addition to the two major compounds, a third minor compound identified as (R)-(-)-5-hydroxymellein (18) was obtained, which was found to be responsible for the significant Wnt inhibition activity recorded. Further studies of this compound and its structural analogs showed that only 18 acts in a highly specific manner, with no acute cytotoxicity. This compound is notably selective for upstream components of the Wnt pathway and is able to inhibit the proliferation of three triple negative breast cancer cell lines. In addition to the discovery of Wnt inhibitors of interest, this study contributes to better characterize the biosynthetic potential of L. venezuelensis.}, } @article {pmid34455760, year = {2021}, author = {Louka, A and Takan, I and Pavlopoulou, A and Georgakilas, AG}, title = {Bioinformatic approaches to the investigation of the atavistic genes implicated in cancer.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {26}, number = {8}, pages = {279-311}, doi = {10.52586/4944}, pmid = {34455760}, issn = {2768-6698}, mesh = {Biological Evolution ; *Computational Biology ; Gene Regulatory Networks ; Humans ; *Neoplasms/genetics ; Phylogeny ; }, abstract = {Introduction: Cancer is a widespread phenomenon occurring across multicellular organisms and represents a condition of atavism, wherein cells follow a path of reverse evolution that unlocks a toolkit of ancient pre-existing adaptations by disturbing hub genes of the human gene network. This results to a primitive cellular phenotype which resembles a unicellular life form. Methods: In the present study, we have employed bioinformatic approaches for the in-depth investigation of twelve atavistic hub genes (ACTG1, CTNNA1, CTNND1, CTTN, DSP, ILK, PKN2, PKP3, PLEC, RCC2, TLN1 and VASP), which exhibit highly disrupted interactions in diverse types of cancer and are associated with the formation of metastasis. To this end, phylogenetic analyses were conducted towards unravelling the evolutionary history of those hubs and tracing the origin of cancer in the Tree of Life. Results: Based on our results, most of those genes are of unicellular origin, and some of them can be traced back to the emergence of cellular life itself (atavistic theory). Our findings indicate how deep the evolutionary roots of cancer actually are, and may be exploited in the clinical setting for the design of novel therapeutic approaches and, particularly, in overcoming resistance to antineoplastic treatment.}, } @article {pmid34440622, year = {2021}, author = {Mandujano-Tinoco, EA and Sultan, E and Ottolenghi, A and Gershoni-Yahalom, O and Rosental, B}, title = {Evolution of Cellular Immunity Effector Cells; Perspective on Cytotoxic and Phagocytic Cellular Lineages.}, journal = {Cells}, volume = {10}, number = {8}, pages = {}, pmid = {34440622}, issn = {2073-4409}, support = {1416/19//Israel Science Foundation/ ; RGY0085/2019//Human Frontier Science Program/ ; }, mesh = {Animals ; Bacteria/immunology/pathogenicity ; *Cell Lineage ; Communicable Diseases/*immunology/metabolism ; *Cytotoxicity, Immunologic ; Host-Pathogen Interactions ; Humans ; *Immunity, Cellular ; *Immunity, Innate ; Parasites/immunology/pathogenicity ; Phagocytes/*immunology/metabolism ; *Phagocytosis ; Signal Transduction ; Viruses/immunology/pathogenicity ; }, abstract = {The immune system has evolved to protect organisms from infections caused by bacteria, viruses, and parasitic pathogens. In addition, it provides regenerative capacities, tissue maintenance, and self/non-self recognition of foreign tissues. Phagocytosis and cytotoxicity are two prominent cellular immune activities positioned at the base of immune effector function in mammals. Although these immune mechanisms have diversified into a wide heterogeneous repertoire of effector cells, it appears that they share some common cellular and molecular features in all animals, but also some interesting convergent mechanisms. In this review, we will explore the current knowledge about the evolution of phagocytic and cytotoxic immune lineages against pathogens, in the clearance of damaged cells, for regeneration, for histocompatibility recognition, and in killing virally infected cells. To this end, we give different immune examples of multicellular organism models, ranging from the roots of bilateral organisms to chordate invertebrates, comparing to vertebrates' lineages. In this review, we compare cellular lineage homologies at the cellular and molecular levels. We aim to highlight and discuss the diverse function plasticity within the evolved immune effector cells, and even suggest the costs and benefits that it may imply for organisms with the meaning of greater defense against pathogens but less ability to regenerate damaged tissues and organs.}, } @article {pmid34430989, year = {2021}, author = {Suthar, J and Al-Jufaili, S and Bray, RA and Frank, M and Theisen, S and Palm, HW}, title = {Redescription of Aspidogaster limacoides Diesing, 1834 (Aspidogastrea: Aspidogastridae) from freshwater fishes of northern Germany.}, journal = {Parasitology research}, volume = {120}, number = {10}, pages = {3405-3416}, pmid = {34430989}, issn = {1432-1955}, support = {MV-II. 12-LM-03//European Fisheries Fund and the Ministry of Agriculture and Environment, Mecklenburg-Western Pomerania as a part of the Project Hygiene management and health concept for surface water-dependent partial circulation systems in M.V./ ; }, mesh = {Animals ; *Cyprinidae ; Fishes ; Fresh Water ; Germany ; Phylogeny ; *Trematoda ; }, abstract = {Aspidogaster limacoides Diesing, 1834 (Aspidogastridae) is redescribed based on light and scanning electron microscopy of specimens from the stomach and intestine of Abramis brama, Rutilus rutilus and Scardinius erythrophthalmus (Actinopterygii: Cyprinidae). The fishes were sampled during 2018 and 2019 at Lake Tollense in Mecklenburg-Western Pomerania, Germany. The prevalence of A. limacoides was highest in R. rutilus (61.7%) followed by Scardinius erythrophthalmus (7.7%) and A. brama (2.9%), while it was absent in Perca fluviatilis from the same lake. The following structures of A. limacoides are described for the first time: a depression on the ventral side of the neck, variations in the number and the arrangement of alveoli, numerous pits scattered all over the body surface, the presence of a few papillae-like structures posterior lateral to the mouth, the number of marginal organs represented by openings of exocrine multicellular glands as shown in histology and the subterminal position of the excretory pore. These characters can be used to distinguish three species of Aspidogaster, namely, A. ijimai, A. conchicola and A. limacoides, suggesting that SEM is a useful and promising tool in differentiating Aspidogaster species. Comparison of molecular data of the ITS1-5.8S-ITS2 regions showed a 94% similarity to A. limacoides from the European part of Russia. Phylogenetic analysis showed that the present specimens clustered in the same clade with A. limacoides sensu stricto, forming a distinct group to the exclusion of congeners.}, } @article {pmid34411089, year = {2021}, author = {Leray, M and Wilkins, LGE and Apprill, A and Bik, HM and Clever, F and Connolly, SR and De León, ME and Duffy, JE and Ezzat, L and Gignoux-Wolfsohn, S and Herre, EA and Kaye, JZ and Kline, DI and Kueneman, JG and McCormick, MK and McMillan, WO and O'Dea, A and Pereira, TJ and Petersen, JM and Petticord, DF and Torchin, ME and Vega Thurber, R and Videvall, E and Wcislo, WT and Yuen, B and Eisen, JA}, title = {Natural experiments and long-term monitoring are critical to understand and predict marine host-microbe ecology and evolution.}, journal = {PLoS biology}, volume = {19}, number = {8}, pages = {e3001322}, pmid = {34411089}, issn = {1545-7885}, mesh = {*Acclimatization ; Animals ; Aquatic Organisms/*microbiology ; *Biological Evolution ; *Ecology ; Ecosystem ; Humans ; *Microbiota ; Symbiosis ; }, abstract = {Marine multicellular organisms host a diverse collection of bacteria, archaea, microbial eukaryotes, and viruses that form their microbiome. Such host-associated microbes can significantly influence the host's physiological capacities; however, the identity and functional role(s) of key members of the microbiome ("core microbiome") in most marine hosts coexisting in natural settings remain obscure. Also unclear is how dynamic interactions between hosts and the immense standing pool of microbial genetic variation will affect marine ecosystems' capacity to adjust to environmental changes. Here, we argue that significantly advancing our understanding of how host-associated microbes shape marine hosts' plastic and adaptive responses to environmental change requires (i) recognizing that individual host-microbe systems do not exist in an ecological or evolutionary vacuum and (ii) expanding the field toward long-term, multidisciplinary research on entire communities of hosts and microbes. Natural experiments, such as time-calibrated geological events associated with well-characterized environmental gradients, provide unique ecological and evolutionary contexts to address this challenge. We focus here particularly on mutualistic interactions between hosts and microbes, but note that many of the same lessons and approaches would apply to other types of interactions.}, } @article {pmid34408733, year = {2021}, author = {Schapheer, C and Pellens, R and Scherson, R}, title = {Arthropod-Microbiota Integration: Its Importance for Ecosystem Conservation.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {702763}, pmid = {34408733}, issn = {1664-302X}, abstract = {Recent reports indicate that the health of our planet is getting worse and that genuine transformative changes are pressing. So far, efforts to ameliorate Earth's ecosystem crises have been insufficient, as these often depart from current knowledge of the underlying ecological processes. Nowadays, biodiversity loss and the alterations in biogeochemical cycles are reaching thresholds that put the survival of our species at risk. Biological interactions are fundamental for achieving biological conservation and restoration of ecological processes, especially those that contribute to nutrient cycles. Microorganism are recognized as key players in ecological interactions and nutrient cycling, both free-living and in symbiotic associations with multicellular organisms. This latter assemblage work as a functional ecological unit called "holobiont." Here, we review the emergent ecosystem properties derived from holobionts, with special emphasis on detritivorous terrestrial arthropods and their symbiotic microorganisms. We revisit their relevance in the cycling of recalcitrant organic compounds (e.g., lignin and cellulose). Finally, based on the interconnection between biodiversity and nutrient cycling, we propose that a multicellular organism and its associates constitute an Ecosystem Holobiont (EH). This EH is the functional unit characterized by carrying out key ecosystem processes. We emphasize that in order to meet the challenge to restore the health of our planet it is critical to reduce anthropic pressures that may threaten not only individual entities (known as "bionts") but also the stability of the associations that give rise to EH and their ecological functions.}, } @article {pmid34404788, year = {2021}, author = {Galindo, LJ and López-García, P and Torruella, G and Karpov, S and Moreira, D}, title = {Phylogenomics of a new fungal phylum reveals multiple waves of reductive evolution across Holomycota.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4973}, pmid = {34404788}, issn = {2041-1723}, mesh = {Basal Bodies ; Blastocladiomycota ; Chytridiomycota/classification ; Flagella ; Fungi/*classification/cytology/genetics/metabolism ; Genomics ; Hepatophyta/*classification ; Hyphae ; Phenotype ; *Phylogeny ; Specimen Handling ; Transcriptome ; }, abstract = {Compared to multicellular fungi and unicellular yeasts, unicellular fungi with free-living flagellated stages (zoospores) remain poorly known and their phylogenetic position is often unresolved. Recently, rRNA gene phylogenetic analyses of two atypical parasitic fungi with amoeboid zoospores and long kinetosomes, the sanchytrids Amoeboradix gromovi and Sanchytrium tribonematis, showed that they formed a monophyletic group without close affinity with known fungal clades. Here, we sequence single-cell genomes for both species to assess their phylogenetic position and evolution. Phylogenomic analyses using different protein datasets and a comprehensive taxon sampling result in an almost fully-resolved fungal tree, with Chytridiomycota as sister to all other fungi, and sanchytrids forming a well-supported, fast-evolving clade sister to Blastocladiomycota. Comparative genomic analyses across fungi and their allies (Holomycota) reveal an atypically reduced metabolic repertoire for sanchytrids. We infer three main independent flagellum losses from the distribution of over 60 flagellum-specific proteins across Holomycota. Based on sanchytrids' phylogenetic position and unique traits, we propose the designation of a novel phylum, Sanchytriomycota. In addition, our results indicate that most of the hyphal morphogenesis gene repertoire of multicellular fungi had already evolved in early holomycotan lineages.}, } @article {pmid34395440, year = {2021}, author = {Richter, M and Piwocka, O and Musielak, M and Piotrowski, I and Suchorska, WM and Trzeciak, T}, title = {From Donor to the Lab: A Fascinating Journey of Primary Cell Lines.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {711381}, pmid = {34395440}, issn = {2296-634X}, abstract = {Primary cancer cell lines are ex vivo cell cultures originating from resected tissues during biopsies and surgeries. Primary cell cultures are objects of intense research due to their high impact on molecular biology and oncology advancement. Initially, the patient-derived specimen must be subjected to dissociation and isolation. Techniques for tumour dissociation are usually reliant on the organisation of connecting tissue. The most common methods include enzymatic digestion (with collagenase, dispase, and DNase), chemical treatment (with ethylene diamine tetraacetic acid and ethylene glycol tetraacetic acid), or mechanical disaggregation to obtain a uniform cell population. Cells isolated from the tissue specimen are cultured as a monolayer or three-dimensional culture, in the form of multicellular spheroids, scaffold-based cultures (i.e., organoids), or matrix-embedded cultures. Every primary cell line must be characterised to identify its origin, purity, and significant features. The process of characterisation should include different assays utilising specific (extra- and intracellular) markers. The most frequently used approaches comprise immunohistochemistry, immunocytochemistry, western blot, flow cytometry, real-time polymerase chain reaction, karyotyping, confocal microscopy, and next-generation sequencing. The growing body of evidence indicates the validity of the usage of primary cancer cell lines in the formulation of novel anti-cancer treatments and their contribution to drug development.}, } @article {pmid34394122, year = {2021}, author = {Sun, V and Sharpley, M and Kaczor-Urbanowicz, KE and Chang, P and Montel-Hagen, A and Lopez, S and Zampieri, A and Zhu, Y and de Barros, SC and Parekh, C and Casero, D and Banerjee, U and Crooks, GM}, title = {The Metabolic Landscape of Thymic T Cell Development In Vivo and In Vitro.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {716661}, pmid = {34394122}, issn = {1664-3224}, support = {P30 AG028748/AG/NIA NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; T32 GM008042/GM/NIGMS NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Biomarkers ; *Cell Differentiation ; Cell Line ; Computational Biology/methods ; *Energy Metabolism ; Gene Expression Profiling ; Hematopoietic Stem Cells/cytology/immunology/metabolism ; Humans ; Lymphopoiesis ; Metabolome ; Metabolomics/methods ; Mice ; Organoids ; T-Lymphocytes/*cytology/*metabolism ; Thymocytes/*cytology/immunology/*metabolism ; Tissue Culture Techniques ; }, abstract = {Although metabolic pathways have been shown to control differentiation and activation in peripheral T cells, metabolic studies on thymic T cell development are still lacking, especially in human tissue. In this study, we use transcriptomics and extracellular flux analyses to investigate the metabolic profiles of primary thymic and in vitro-derived mouse and human thymocytes. Core metabolic pathways, specifically glycolysis and oxidative phosphorylation, undergo dramatic changes between the double-negative (DN), double-positive (DP), and mature single-positive (SP) stages in murine and human thymus. Remarkably, despite the absence of the complex multicellular thymic microenvironment, in vitro murine and human T cell development recapitulated the coordinated decrease in glycolytic and oxidative phosphorylation activity between the DN and DP stages seen in primary thymus. Moreover, by inducing in vitro T cell differentiation from Rag1[-/-] mouse bone marrow, we show that reduced metabolic activity at the DP stage is independent of TCR rearrangement. Thus, our findings suggest that highly conserved metabolic transitions are critical for thymic T cell development.}, } @article {pmid34385986, year = {2021}, author = {Zhang, W and Wang, Y and Liu, L and Pan, Y and Lin, W}, title = {Identification and Genomic Characterization of Two Previously Unknown Magnetotactic Nitrospirae.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {690052}, pmid = {34385986}, issn = {1664-302X}, abstract = {Magnetotactic bacteria (MTB) are a group of microbes that biomineralize membrane-bound, nanosized magnetite (Fe3O4), and/or greigite (Fe3S4) crystals in intracellular magnetic organelle magnetosomes. MTB belonging to the Nitrospirae phylum can form up to several hundreds of Fe3O4 magnetosome crystals and dozens of sulfur globules in a single cell. These MTB are widespread in aquatic environments and sometimes account for a significant proportion of microbial biomass near the oxycline, linking these lineages to the key steps of global iron and sulfur cycling. Despite their ecological and biogeochemical importance, our understanding of the diversity and ecophysiology of magnetotactic Nitrospirae is still very limited because this group of MTB remains unculturable. Here, we identify and characterize two previously unknown MTB populations within the Nitrospirae phylum through a combination of 16S rRNA gene-based and genome-resolved metagenomic analyses. These two MTB populations represent distinct morphotypes (rod-shaped and coccoid, designated as XYR, and XYC, respectively), and both form more than 100 bullet-shaped magnetosomal crystals per cell. High-quality draft genomes of XYR and XYC have been reconstructed, and they represent a novel species and a novel genus, respectively, according to their average amino-acid identity values with respect to available genomes. Accordingly, the names Candidatus Magnetobacterium cryptolimnobacter and Candidatus Magnetomicrobium cryptolimnococcus for XYR and XYC, respectively, were proposed. Further comparative genomic analyses of XYR, XYC, and previously reported magnetotactic Nitrospirae reveal the general metabolic potential of this MTB group in distinct microenvironments, including CO2 fixation, dissimilatory sulfate reduction, sulfide oxidation, nitrogen fixation, or denitrification processes. A remarkably conserved magnetosome gene cluster has been identified across Nitrospirae MTB genomes, indicating its putative important adaptive roles in these bacteria. Taken together, the present study provides novel insights into the phylogenomic diversity and ecophysiology of this intriguing, yet poorly understood MTB group.}, } @article {pmid34384851, year = {2021}, author = {Cisbani, G and Metherel, AH and Smith, ME and Bazinet, RP}, title = {Murine and human microglial cells are relatively enriched with eicosapentaenoic acid compared to the whole brain.}, journal = {Neurochemistry international}, volume = {150}, number = {}, pages = {105154}, doi = {10.1016/j.neuint.2021.105154}, pmid = {34384851}, issn = {1872-9754}, support = {//CIHR/Canada ; }, mesh = {Animals ; Brain/cytology/*metabolism ; Brain Chemistry/*physiology ; Eicosapentaenoic Acid/analysis/*metabolism ; Female ; Fetus ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Microglia/chemistry/*metabolism ; }, abstract = {The brain is a multicellular organ enriched with lipids. While the fatty acid composition of gross cerebral tissue is well characterized, the fatty acid composition of specific brain cells, particularly microglia cells, is less well characterized. Microglia cells are the innate immune cells of the brain, and a paucity of studies measuring their fatty acid composition using either immortalized or primary microglia cells report a higher ratio of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) than widely observed in whole brain tissue. Here we further characterize the fatty acid composition of murine microglia cells from young male and female mice as well as of human origin and compared it with a myelin-enriched fraction from the same mice. Our results show that saturated and monounsaturated fatty acids are the most abundant followed by polyunsaturated fatty acids (PUFA), with no statistical differences between sexes. Regarding PUFA, although DHA levels did not differ between human and murine cells, EPA was statistically higher in murine microglia. Notably, the DHA to EPA ratio was about 400 times lower in microglial cells compared to the myelin-enriched fraction. Thus, our results suggest that as compared to whole brain tissue EPA is relatively abundant in microglia cells, particularly in comparison to other n-3 PUFA such as DHA. Since the fatty acid composition of microglia can influence their functionality, a better understanding of EPA and DHA metabolism in microglia and the brain could identify new targets to modify microglial activity.}, } @article {pmid34382225, year = {2021}, author = {Baluška, F and Reber, AS}, title = {CBC-Clock Theory of Life - Integration of cellular circadian clocks and cellular sentience is essential for cognitive basis of life.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {10}, pages = {e2100121}, doi = {10.1002/bies.202100121}, pmid = {34382225}, issn = {1521-1878}, mesh = {*Circadian Clocks ; Circadian Rhythm ; Cognition ; Oxidation-Reduction ; Photosynthesis ; }, abstract = {Cellular circadian clocks represent ancient anticipatory systems which co-evolved with the first cells to safeguard their survival. Cyanobacteria represent one of the most ancient cells, having essentially invented photosynthesis together with redox-based cellular circadian clocks some 2.7 billion years ago. Bioelectricity phenomena, based on redox homeostasis associated electron transfers in membranes and within protein complexes inserted in excitable membranes, play important roles, not only in the cellular circadian clocks and in anesthetics-sensitive cellular sentience (awareness of environment), but also in the coupling of single cells into tissues and organs of unitary multicellular organisms. This integration of cellular circadian clocks with cellular basis of sentience is an essential feature of the cognitive CBC-Clock basis of cellular life.}, } @article {pmid34374500, year = {2021}, author = {Dzik, J}, title = {Metabolic evolutionary roots of the macrophage immune response in amoeba-bacteria interactions: The conserved role of hypoxia-induced Factor and AMP kinase.}, journal = {Acta biochimica Polonica}, volume = {68}, number = {3}, pages = {457-476}, doi = {10.18388/abp.2020_5683}, pmid = {34374500}, issn = {1734-154X}, mesh = {Adenylate Kinase/*metabolism ; Amoeba/immunology/*metabolism ; Animals ; Bacteria/immunology/*metabolism ; Cytokines/metabolism ; Glycolysis ; Humans ; Hypoxia/metabolism ; Hypoxia-Inducible Factor 1/*metabolism ; Immunity/immunology ; Legionella/immunology/metabolism ; Macrophages/*immunology ; NF-kappa B/metabolism ; Phagocytosis ; Toll-Like Receptors/metabolism ; }, abstract = {The bacteria Legionella, being able to infect both macrophages and protozoans, reduce oxidative phosphorylation and induce glycolysis, which allows pathogens to grow and replicate in these cells. In amoeba-like inflammatory macrophages (M1), the phagocytizing cells of the primary immune defense, an increase in the rate of glycolysis is followed by a decrease of oxidative phosphorylation. The opposite takes place in anti-inflammatory macrophages (M2). They change from glycolysis to oxidative metabolism when AMP-dependent kinase (AMPK) is activated by a high ratio of AMP/ATP. Stimulation of macrophages with anti-inflammatory cytokines causes activation of AMPK. Infection of macrophages with the parasitic flagellate Leishmania infantum induces a switch from an initial glycolytic phase to oxidative phase with the essential role of AMPK in this change. Activated AMPK induces catabolic pathways effectively producing ATP as well as processes requiring the energy supply. AMPK regulates the migration of cells and enhances the phagocytic activity of macrophages. In macrophages, bacterial products activate TLRs and NF-κB signaling, causing an increase of transcription of hypoxia-induced factor HIF-1α (a subunit of HIF-1). This brings about induction of the enzyme and transporter expression essential for glycolysis and the pentose phosphate pathway to proceed and makes biosynthetic processes and ROS production in macrophages possible. Hypoxia augments macrophage phagocytosis in a HIF-1α-dependent manner. Multicellular parasites experience changes in the availability of oxygen in their life cycle. In the nematode Ascaris suum, HIF participates in the pre-adaptation to hypoxic conditions after infection of their hosts. Also, the freshwater and marine invertebrates meet changes of oxygen concentrations. In the anaerobic branch of the respiratory chain of these invertebrates, fumarate serves as the terminal electron acceptor that is reduced to succinate in complex II of the ETC. In mammalian cells, accumulation of succinate under hypoxic conditions suggests that the mammalian complex II may reduce fumarate to succinate, too. The data reviewed here show that the ability to shift the cell metabolism towards glycolysis observed in activated macrophages can be traced back in evolution to metabolic changes characterizing protozoans infected with bacteria. Anabolic needs of multiplying bacteria direct host metabolism to glycolysis that produces, aside from ATP, precursors of the amino acids used by the pathogen for its protein synthesis. M1-activated mammalian macrophages behave in the same way. Regulation of metabolism in M1 and M2 macrophages is further enhanced by HIF-1 and AMPK, respectively. These archaic functions of AMPK and HIF, important also to control phagocytosis and cell migration were extended to embryonic development in multicellular organisms.}, } @article {pmid34373443, year = {2021}, author = {Cao, Q and Wu, S and Xiao, C and Chen, S and Chi, X and Cui, X and Tang, H and Su, W and Zheng, Y and Zhong, J and Li, Z and Li, F and Chen, H and Hou, L and Wang, H and Wen, W}, title = {Integrated single-cell analysis revealed immune dynamics during Ad5-nCoV immunization.}, journal = {Cell discovery}, volume = {7}, number = {1}, pages = {64}, pmid = {34373443}, issn = {2056-5968}, support = {81722034//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81988101//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81802878//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81670015//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2018ZX09101002//Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)/ ; 2018ZX10732202-002-001//Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)/ ; }, abstract = {Coronavirus disease 2019 (COVID-19), driven by SARS-CoV-2, is a severe infectious disease that has become a global health threat. Vaccines are among the most effective public health tools for combating COVID-19. Immune status is critical for evaluating the safety and response to the vaccine, however, the evolution of the immune response during immunization remains poorly understood. Single-cell RNA sequencing (scRNA-seq) represents a powerful tool for dissecting multicellular behavior and discovering therapeutic antibodies. Herein, by performing scRNA/V(D)J-seq on peripheral blood mononuclear cells from four COVID-19 vaccine trial participants longitudinally during immunization, we revealed enhanced cellular immunity with concerted and cell type-specific IFN responses as well as boosted humoral immunity with SARS-CoV-2-specific antibodies. Based on the CDR3 sequence and germline enrichment, we were able to identify several potential binding antibodies. We synthesized, expressed and tested 21 clones from the identified lineages. Among them, one monoclonal antibody (P3V6-1) exhibited relatively high affinity with the extracellular domain of Spike protein, which might be a promising therapeutic reagent for COVID-19. Overall, our findings provide insights for assessing vaccine through the novel scRNA/V(D)J-seq approach, which might facilitate the development of more potent, durable and safe prophylactic vaccines.}, } @article {pmid34371024, year = {2021}, author = {Bussey, KJ and Davies, PCW}, title = {Reverting to single-cell biology: The predictions of the atavism theory of cancer.}, journal = {Progress in biophysics and molecular biology}, volume = {165}, number = {}, pages = {49-55}, pmid = {34371024}, issn = {1873-1732}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; }, mesh = {Bacteria/genetics ; Biological Evolution ; Gene Regulatory Networks ; Humans ; *Neoplasms/genetics ; Phenotype ; }, abstract = {Cancer or cancer-like phenomena pervade multicellular life, implying deep evolutionary roots. Many of the hallmarks of cancer recapitulate unicellular modalities, suggesting that cancer initiation and progression represent a systematic reversion to simpler ancestral phenotypes in response to a stress or insult. This so-called atavism theory may be tested using phylostratigraphy, which can be used to assign ages to genes. Several research groups have confirmed that cancer cells tend to over-express evolutionary older genes, and rewire the architecture linking unicellular and multicellular gene networks. In addition, some of the elevated mutation rate - a well-known hallmark of cancer - is actually self-inflicted, driven by genes found to be homologs of the ancient SOS genes activated in stressed bacteria, and employed to evolve biological workarounds. These findings have obvious implications for therapy.}, } @article {pmid34359962, year = {2021}, author = {Van Goor, J and Shakes, DC and Haag, ES}, title = {Fisher vs. the Worms: Extraordinary Sex Ratios in Nematodes and the Mechanisms that Produce Them.}, journal = {Cells}, volume = {10}, number = {7}, pages = {}, pmid = {34359962}, issn = {2073-4409}, support = {IOS-1755379//National Science Foundation/ ; IOS-1122101//National Science Foundation/ ; }, mesh = {Animals ; Fertility/*physiology ; Humans ; Male ; Nematoda/*metabolism ; Reproduction/*physiology ; Selection, Genetic ; *Sex Ratio ; Spermatozoa/cytology ; }, abstract = {Parker, Baker, and Smith provided the first robust theory explaining why anisogamy evolves in parallel in multicellular organisms. Anisogamy sets the stage for the emergence of separate sexes, and for another phenomenon with which Parker is associated: sperm competition. In outcrossing taxa with separate sexes, Fisher proposed that the sex ratio will tend towards unity in large, randomly mating populations due to a fitness advantage that accrues in individuals of the rarer sex. This creates a vast excess of sperm over that required to fertilize all available eggs, and intense competition as a result. However, small, inbred populations can experience selection for skewed sex ratios. This is widely appreciated in haplodiploid organisms, in which females can control the sex ratio behaviorally. In this review, we discuss recent research in nematodes that has characterized the mechanisms underlying highly skewed sex ratios in fully diploid systems. These include self-fertile hermaphroditism and the adaptive elimination of sperm competition factors, facultative parthenogenesis, non-Mendelian meiotic oddities involving the sex chromosomes, and environmental sex determination. By connecting sex ratio evolution and sperm biology in surprising ways, these phenomena link two "seminal" contributions of G. A. Parker.}, } @article {pmid34356075, year = {2021}, author = {Kloareg, B and Badis, Y and Cock, JM and Michel, G}, title = {Role and Evolution of the Extracellular Matrix in the Acquisition of Complex Multicellularity in Eukaryotes: A Macroalgal Perspective.}, journal = {Genes}, volume = {12}, number = {7}, pages = {}, pmid = {34356075}, issn = {2073-4425}, mesh = {Animals ; *Biological Evolution ; Eukaryota/classification/*physiology ; Extracellular Matrix/*physiology ; Seaweed/classification/*physiology ; }, abstract = {Multicellular eukaryotes are characterized by an expanded extracellular matrix (ECM) with a diversified composition. The ECM is involved in determining tissue texture, screening cells from the outside medium, development, and innate immunity, all of which are essential features in the biology of multicellular eukaryotes. This review addresses the origin and evolution of the ECM, with a focus on multicellular marine algae. We show that in these lineages the expansion of extracellular matrix played a major role in the acquisition of complex multicellularity through its capacity to connect, position, shield, and defend the cells. Multiple innovations were necessary during these evolutionary processes, leading to striking convergences in the structures and functions of the ECMs of algae, animals, and plants.}, } @article {pmid34356071, year = {2021}, author = {Petroll, R and Schreiber, M and Finke, H and Cock, JM and Gould, SB and Rensing, SA}, title = {Signatures of Transcription Factor Evolution and the Secondary Gain of Red Algae Complexity.}, journal = {Genes}, volume = {12}, number = {7}, pages = {}, pmid = {34356071}, issn = {2073-4425}, mesh = {*Evolution, Molecular ; *Genetic Variation ; *Genome ; *Phylogeny ; Rhodophyta/chemistry/*classification/*genetics/metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Red algae (Rhodophyta) belong to the superphylum Archaeplastida, and are a species-rich group exhibiting diverse morphologies. Theory has it that the unicellular red algal ancestor went through a phase of genome contraction caused by adaptation to extreme environments. More recently, the classes Porphyridiophyceae, Bangiophyceae, and Florideophyceae experienced genome expansions, coinciding with an increase in morphological complexity. Transcription-associated proteins (TAPs) regulate transcription, show lineage-specific patterns, and are related to organismal complexity. To better understand red algal TAP complexity and evolution, we investigated the TAP family complement of uni- and multi-cellular red algae. We found that the TAP family complement correlates with gain of morphological complexity in the multicellular Bangiophyceae and Florideophyceae, and that abundance of the C2H2 zinc finger transcription factor family may be associated with the acquisition of morphological complexity. An expansion of heat shock transcription factors (HSF) occurred within the unicellular Cyanidiales, potentially as an adaption to extreme environmental conditions.}, } @article {pmid34354328, year = {2021}, author = {Zion, E and Chen, X}, title = {Breaking Symmetry: The Asymmetries in Epigenetic Inheritance.}, journal = {The biochemist}, volume = {43}, number = {1}, pages = {14-19}, pmid = {34354328}, issn = {0954-982X}, support = {F31 DK122702/DK/NIDDK NIH HHS/United States ; R35 GM127075/GM/NIGMS NIH HHS/United States ; T32 GM007231/GM/NIGMS NIH HHS/United States ; }, abstract = {Symmetry and asymmetry are fundamental aspects of life. Most cells within a multicellular organism contain the same genetic information, passed on from one originating cell - the zygote; however, these cells can take on a variety of different identities, with diverse appearances and functions. A fundamental question in biology ponders how cells containing identical DNA content can take on different cell identities. Epigenetic mechanisms could be the symmetry breaking factor, as they are able to change gene expression in cells without changing the DNA sequence. While the process of duplication and segregation of DNA during cell division has been well studied, it is less understood how the epigenetic information is established and inherited in the cells within a multicellular organism. Studies of asymmetric stem cell division, where a stem cell division gives rise to a self-renewed stem cell and a differentiating daughter cell, provides a model to study how epigenetic information is maintained or changed to produce daughter cells with identical genetic information but distinct cell fates. Here, we discuss findings and ideas of how epigenetic information is maintained or changed during asymmetric cell division and the importance of this asymmetry in influencing cell fate.}, } @article {pmid34343611, year = {2021}, author = {Moroz, LL and Nikitin, MA and Poličar, PG and Kohn, AB and Romanova, DY}, title = {Evolution of glutamatergic signaling and synapses.}, journal = {Neuropharmacology}, volume = {199}, number = {}, pages = {108740}, pmid = {34343611}, issn = {1873-7064}, support = {R01 NS114491/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Glutamic Acid/*physiology ; Receptors, Glutamate/*physiology ; Signal Transduction/*physiology ; Synapses/*physiology ; }, abstract = {Glutamate (Glu) is the primary excitatory transmitter in the mammalian brain. But, we know little about the evolutionary history of this adaptation, including the selection of l-glutamate as a signaling molecule in the first place. Here, we used comparative metabolomics and genomic data to reconstruct the genealogy of glutamatergic signaling. The origin of Glu-mediated communications might be traced to primordial nitrogen and carbon metabolic pathways. The versatile chemistry of L-Glu placed this molecule at the crossroad of cellular biochemistry as one of the most abundant metabolites. From there, innovations multiplied. Many stress factors or injuries could increase extracellular glutamate concentration, which led to the development of modular molecular systems for its rapid sensing in bacteria and archaea. More than 20 evolutionarily distinct families of ionotropic glutamate receptors (iGluRs) have been identified in eukaryotes. The domain compositions of iGluRs correlate with the origins of multicellularity in eukaryotes. Although L-Glu was recruited as a neuro-muscular transmitter in the early-branching metazoans, it was predominantly a non-neuronal messenger, with a possibility that glutamatergic synapses evolved more than once. Furthermore, the molecular secretory complexity of glutamatergic synapses in invertebrates (e.g., Aplysia) can exceed their vertebrate counterparts. Comparative genomics also revealed 15+ subfamilies of iGluRs across Metazoa. However, most of this ancestral diversity had been lost in the vertebrate lineage, preserving AMPA, Kainate, Delta, and NMDA receptors. The widespread expansion of glutamate synapses in the cortical areas might be associated with the enhanced metabolic demands of the complex brain and compartmentalization of Glu signaling within modular neuronal ensembles.}, } @article {pmid34343465, year = {2021}, author = {Anda, S and Boye, E and Schink, KO and Grallert, B}, title = {Cosegregation of asymmetric features during cell division.}, journal = {Open biology}, volume = {11}, number = {8}, pages = {210116}, pmid = {34343465}, issn = {2046-2441}, mesh = {*Cell Division ; Centrosome/*physiology ; *Chromosome Segregation ; Chromosomes, Fungal/*genetics ; *Mitosis ; Schizosaccharomyces/*physiology ; Spindle Apparatus/*physiology ; }, abstract = {Cellular asymmetry plays a major role in the ageing and evolution of multicellular organisms. However, it remains unknown how the cell distinguishes 'old' from 'new' and whether asymmetry is an attribute of highly specialized cells or a feature inherent in all cells. Here, we investigate the segregation of three asymmetric features: old and new DNA, the spindle pole body (SPB, the centrosome analogue) and the old and new cell ends, using a simple unicellular eukaryote, Schizosaccharomyces pombe. To our knowledge, this is the first study exploring three asymmetric features in the same cells. We show that of the three chromosomes of S. pombe, chromosome I containing the new parental strand, preferentially segregated to the cells inheriting the old cell end. Furthermore, the new SPB also preferentially segregated to the cells inheriting the old end. Our results suggest that the ability to distinguish 'old' from 'new' and to segregate DNA asymmetrically are inherent features even in simple unicellular eukaryotes.}, } @article {pmid34343062, year = {2021}, author = {Li, XG and Tang, HZ and Zhang, WJ and Qi, XQ and Qu, ZG and Xu, J and Wu, LF}, title = {Thermococcus aciditolerans sp. nov., a piezotolerant, hyperthermophilic archaeon isolated from a deep-sea hydrothermal vent chimney in the Southwest Indian Ridge.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {71}, number = {8}, pages = {}, doi = {10.1099/ijsem.0.004934}, pmid = {34343062}, issn = {1466-5034}, mesh = {Base Composition ; DNA, Archaeal/genetics ; *Hydrothermal Vents/microbiology ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; *Thermococcus/classification/isolation & purification ; }, abstract = {A hyperthermophilic, strictly anaerobic archaeon, designated strain SY113[T], was isolated from a deep-sea hydrothermal vent chimney on the Southwest Indian Ridge at a water depth of 2770 m. Enrichment and isolation of strain SY113[T] were performed at 85 °C at 0.1 MPa. Cells of strain SY113[T] were irregular motile cocci with peritrichous flagella and generally 0.8-2.4 µm in diameter. Growth was observed at temperatures between 50 and 90 °C (optimum at 85 °C) and under hydrostatic pressures of 0.1-60 MPa (optimum, 27 MPa). Cells of SY113[T] grew at pH 4.0-9.0 (optimum, pH 5.5) and a NaCl concentration of 0.5-5.5 % (w/v; optimum concentration, 3.0 % NaCl). Strain SY113[T] was an anaerobic chemoorganoheterotroph and grew on complex proteinaceous substrates such as yeast extract and tryptone, as well as on maltose and starch. Elemental sulphur stimulated growth, but not obligatory for its growth. The G+C content of the genomic DNA was 55.0 mol%. Phylogenetic analysis of the 16S rRNA sequence of strain SY113[T] showed that the novel isolate belonged to the genus Thermococcus. On the basis of physiological characteristics, average nucleotide identity values and in silico DNA-DNA hybridization results, we propose a novel species, named Thermococcus aciditolerans sp. nov. The type strain is SY113[T] (=MCCC 1K04190[T]=JCM 39083[T]).}, } @article {pmid34338785, year = {2022}, author = {Ramalho, JJ and Jones, VAS and Mutte, S and Weijers, D}, title = {Pole position: How plant cells polarize along the axes.}, journal = {The Plant cell}, volume = {34}, number = {1}, pages = {174-192}, pmid = {34338785}, issn = {1532-298X}, mesh = {Biological Evolution ; *Cell Polarity ; *Phylogeny ; Plant Cells/*physiology ; *Plant Physiological Phenomena ; Plant Proteins/*classification ; }, abstract = {Having a sense of direction is a fundamental cellular trait that can determine cell shape, division orientation, or function, and ultimately the formation of a functional, multicellular body. Cells acquire and integrate directional information by establishing discrete subcellular domains along an axis with distinct molecular profiles, a process known as cell polarization. Insight into the principles and mechanisms underlying cell polarity has been propelled by decades of extensive research mostly in yeast and animal models. Our understanding of cell polarity establishment in plants, which lack most of the regulatory molecules identified in other eukaryotes, is more limited, but significant progress has been made in recent years. In this review, we explore how plant cells coordinately establish stable polarity axes aligned with the organ axes, highlighting similarities in the molecular logic used to polarize both plant and animal cells. We propose a classification system for plant cell polarity events and nomenclature guidelines. Finally, we provide a deep phylogenetic analysis of polar proteins and discuss the evolution of polarity machineries in plants.}, } @article {pmid34332367, year = {2021}, author = {Thorup, C and Petro, C and Bøggild, A and Ebsen, TS and Brokjær, S and Nielsen, LP and Schramm, A and Bjerg, JJ}, title = {How to grow your cable bacteria: Establishment of a stable single-strain culture in sediment and proposal of Candidatus Electronema aureum GS.}, journal = {Systematic and applied microbiology}, volume = {44}, number = {5}, pages = {126236}, doi = {10.1016/j.syapm.2021.126236}, pmid = {34332367}, issn = {1618-0984}, support = {291650/ERC_/European Research Council/International ; }, mesh = {*Bacteriological Techniques ; Base Composition ; DNA, Bacterial/genetics ; *Deltaproteobacteria/classification/growth & development ; *Geologic Sediments/microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Cable bacteria are multicellular filamentous bacteria within the Desulfobulbaceae that couple the oxidation of sulfide to the reduction of oxygen over centimeter distances via long distance electron transport (LDET). So far, none of the freshwater or marine cable bacteria species have been isolated into pure culture. Here we describe a method for establishing a stable single-strain cable bacterium culture in partially sterilized sediment. By repeated transfers of a single cable bacterium filament from freshwater pond sediment into autoclaved sediment, we obtained strain GS, identified by its 16S rRNA gene as a member of Ca. Electronema. This strain was further propagated by transferring sediment clumps, and has now been stable within its semi-natural microbial community for several years. Its metagenome-assembled genome was 93% complete, had a size of 2.76 Mbp, and a DNA G + C content of 52%. Average Nucleotide Identity (ANI) and Average Amino Acid Identity (AAI) suggest the affiliation of strain GS to Ca. Electronema as a novel species. Cell size, number of outer ridges, and detection of LDET in the GS culture are likewise consistent with Ca. Electronema. Based on these combined features, we therefore describe strain GS as a new cable bacterium species of the candidate genus Electronema, for which we propose the name Candidatus Electronema aureum sp.nov. Although not a pure culture, this stable single-strain culture will be useful for physiological and omics-based studies; similar approaches with single-cell or single-filament transfers into natural medium may also aid the characterization of other difficult-to-culture microbes.}, } @article {pmid34319226, year = {2021}, author = {Zhang, WJ and Zhang, C and Zhou, S and Li, XG and Mangenot, S and Fouteau, S and Guerin, T and Qi, XQ and Yang, J and Bartlett, DH and Wu, LF}, title = {Comparative genomic analysis of obligately piezophilic Moritella yayanosii DB21MT-5 reveals bacterial adaptation to the Challenger Deep, Mariana Trench.}, journal = {Microbial genomics}, volume = {7}, number = {7}, pages = {}, pmid = {34319226}, issn = {2057-5858}, mesh = {Acclimatization/*genetics ; Choline/metabolism ; Ecosystem ; Energy Metabolism/*genetics ; Fermentation/genetics/physiology ; Genome, Bacterial/*genetics ; Hydrostatic Pressure ; Moritella/*genetics/physiology ; Oceans and Seas ; Water Microbiology ; Whole Genome Sequencing ; }, abstract = {Hadal trenches are the deepest but underexplored ecosystems on the Earth. Inhabiting the trench bottom is a group of micro-organisms termed obligate piezophiles that grow exclusively under high hydrostatic pressures (HHP). To reveal the genetic and physiological characteristics of their peculiar lifestyles and microbial adaptation to extreme high pressures, we sequenced the complete genome of the obligately piezophilic bacterium Moritella yayanosii DB21MT-5 isolated from the deepest oceanic sediment at the Challenger Deep, Mariana Trench. Through comparative analysis against pressure sensitive and deep-sea piezophilic Moritella strains, we identified over a hundred genes that present exclusively in hadal strain DB21MT-5. The hadal strain encodes fewer signal transduction proteins and secreted polysaccharases, but has more abundant metal ion transporters and the potential to utilize plant-derived saccharides. Instead of producing osmolyte betaine from choline as other Moritella strains, strain DB21MT-5 ferments on choline within a dedicated bacterial microcompartment organelle. Furthermore, the defence systems possessed by DB21MT-5 are distinct from other Moritella strains but resemble those in obligate piezophiles obtained from the same geographical setting. Collectively, the intensive comparative genomic analysis of an obligately piezophilic strain Moritella yayanosii DB21MT-5 demonstrates a depth-dependent distribution of energy metabolic pathways, compartmentalization of important metabolism and use of distinct defence systems, which likely contribute to microbial adaptation to the bottom of hadal trench.}, } @article {pmid34315265, year = {2021}, author = {Chen, L and Wiens, JJ}, title = {Multicellularity and sex helped shape the Tree of Life.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1955}, pages = {20211265}, pmid = {34315265}, issn = {1471-2954}, mesh = {*Biodiversity ; Genetic Speciation ; Phenotype ; Phylogeny ; *Reproduction ; }, abstract = {Across the Tree of Life, there are dramatic differences in species numbers among groups. However, the factors that explain the differences among the deepest branches have remained unknown. We tested whether multicellularity and sexual reproduction might explain these patterns, since the most species-rich groups share these traits. We found that groups with multicellularity and sexual reproduction have accelerated rates of species proliferation (diversification), and that multicellularity has a stronger effect than sexual reproduction. Patterns of species richness among clades are then strongly related to these differences in diversification rates. Taken together, these results help explain patterns of biodiversity among groups of organisms at the very broadest scales. They may also help explain the mysterious preponderance of sexual reproduction among species (the 'paradox of sex') by showing that organisms with sexual reproduction proliferate more rapidly.}, } @article {pmid34302147, year = {2021}, author = {Zhao, YG and Codogno, P and Zhang, H}, title = {Machinery, regulation and pathophysiological implications of autophagosome maturation.}, journal = {Nature reviews. Molecular cell biology}, volume = {22}, number = {11}, pages = {733-750}, pmid = {34302147}, issn = {1471-0080}, mesh = {Autophagosomes/*genetics ; Autophagy/*genetics ; Endosomes/genetics ; Humans ; Lysosomes/genetics ; Neurodegenerative Diseases/*genetics/pathology ; Phagosomes/genetics ; Protein Processing, Post-Translational/genetics ; SNARE Proteins/genetics ; Transport Vesicles/*genetics ; rab GTP-Binding Proteins/genetics ; }, abstract = {Autophagy is a versatile degradation system for maintaining cellular homeostasis whereby cytosolic materials are sequestered in a double-membrane autophagosome and subsequently delivered to lysosomes, where they are broken down. In multicellular organisms, newly formed autophagosomes undergo a process called 'maturation', in which they fuse with vesicles originating from endolysosomal compartments, including early/late endosomes and lysosomes, to form amphisomes, which eventually become degradative autolysosomes. This fusion process requires the concerted actions of multiple regulators of membrane dynamics, including SNAREs, tethering proteins and RAB GTPases, and also transport of autophagosomes and late endosomes/lysosomes towards each other. Multiple mechanisms modulate autophagosome maturation, including post-translational modification of key components, spatial distribution of phosphoinositide lipid species on membranes, RAB protein dynamics, and biogenesis and function of lysosomes. Nutrient status and various stresses integrate into the autophagosome maturation machinery to coordinate the progression of autophagic flux. Impaired autophagosome maturation is linked to the pathogenesis of various human diseases, including neurodegenerative disorders, cancer and myopathies. Furthermore, invading pathogens exploit various strategies to block autophagosome maturation, thus evading destruction and even subverting autophagic vacuoles (autophagosomes, amphisomes and autolysosomes) for survival, growth and/or release. Here, we discuss the recent progress in our understanding of the machinery and regulation of autophagosome maturation, the relevance of these mechanisms to human pathophysiology and how they are harnessed by pathogens for their benefit. We also provide perspectives on targeting autophagosome maturation therapeutically.}, } @article {pmid34301628, year = {2021}, author = {Waldvogel, AM and Pfenninger, M}, title = {Temperature dependence of spontaneous mutation rates.}, journal = {Genome research}, volume = {31}, number = {9}, pages = {1582-1589}, pmid = {34301628}, issn = {1549-5469}, mesh = {Evolution, Molecular ; Mutation ; *Mutation Accumulation ; *Mutation Rate ; Temperature ; }, abstract = {Mutation is the source of genetic variation and the fundament of evolution. Temperature has long been suggested to have a direct impact on realized spontaneous mutation rates. If mutation rates vary in response to environmental conditions, such as the variation of the ambient temperature through space and time, they should no longer be described as species-specific constants. By combining mutation accumulation with whole-genome sequencing in a multicellular organism, we provide empirical support to reject the null hypothesis of a constant, temperature-independent mutation rate. Instead, mutation rates depended on temperature in a U-shaped manner with increasing rates toward both temperature extremes. This relation has important implications for mutation-dependent processes in molecular evolution, processes shaping the evolution of mutation rates, and even the evolution of biodiversity as such.}, } @article {pmid34293333, year = {2021}, author = {Kożyczkowska, A and Najle, SR and Ocaña-Pallarès, E and Aresté, C and Shabardina, V and Ara, PS and Ruiz-Trillo, I and Casacuberta, E}, title = {Stable transfection in protist Corallochytrium limacisporum identifies novel cellular features among unicellular animals relatives.}, journal = {Current biology : CB}, volume = {31}, number = {18}, pages = {4104-4110.e5}, doi = {10.1016/j.cub.2021.06.061}, pmid = {34293333}, issn = {1879-0445}, mesh = {Animals ; Cell Nucleus Division ; *Eukaryota/genetics ; *Fungi/genetics ; Phylogeny ; Transfection ; }, abstract = {The evolutionary path from protists to multicellular animals remains a mystery. Recent work on the genomes of several unicellular relatives of animals has shaped our understanding of the genetic changes that may have occurred in this transition.[1-3] However, the specific cellular modifications that took place to accommodate these changes remain unclear. To address this, we need to compare metazoan cells with those of their extant relatives, which are choanoflagellates, filastereans, ichthyosporeans, and corallochytreans/pluriformeans. Interestingly, these lineages display a range of developmental patterns potentially homologous to animal ones. Genetic tools have already been established in three of those lineages.[4-7] However, there are no genetic tools available for Corallochytrea. We here report the development of stable transfection in the corallochytrean Corallochytrium limacisporum. Using these tools, we discern previously unknown biological features of C. limacisporum. In particular, we identify two different paths for cell division-binary fission and coenocytic growth-that reveal a non-linear life cycle. Additionally, we found that C. limacisporum is binucleate for most of its life cycle, and that, contrary to what happens in most eukaryotes, nuclear division is decoupled from cellular division. Moreover, its actin cytoskeleton shares characteristics with both fungal and animal cells. The establishment of these tools in C. limacisporum fills an important gap in the unicellular relatives of animals, opening up new avenues of research to elucidate the specific cellular changes that occurred in the evolution of animals.}, } @article {pmid34279742, year = {2021}, author = {de Souza, ID and Reis, CF and Morais, DAA and Fernandes, VGS and Cavalcante, JVF and Dalmolin, RJS}, title = {Ancestry analysis indicates two different sets of essential genes in eukaryotic model species.}, journal = {Functional & integrative genomics}, volume = {21}, number = {3-4}, pages = {523-531}, pmid = {34279742}, issn = {1438-7948}, support = {308258/2018-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Drosophila melanogaster/genetics ; *Evolution, Molecular ; *Genes, Essential ; Mice ; *Saccharomyces cerevisiae/genetics ; *Schizosaccharomyces/genetics ; }, abstract = {Essential genes are so-called because they are crucial for organism perpetuation. Those genes are usually related to essential functions to cellular metabolism or multicellular homeostasis. Deleterious alterations on essential genes produce a spectrum of phenotypes in multicellular organisms. The effects range from the impairment of the fertilization process, disruption of fetal development, to loss of reproductive capacity. Essential genes are described as more evolutionarily conserved than non-essential genes. However, there is no consensus about the relationship between gene essentiality and gene age. Here, we identified essential genes in five model eukaryotic species (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster, Caenorhabditis elegans, and Mus musculus) and estimate their evolutionary ancestry and their network properties. We observed that essential genes, on average, are older than other genes in all species investigated. The relationship of network properties and gene essentiality convey with previous findings, showing essential genes as important nodes in biological networks. As expected, we also observed that essential orthologs shared by the five species evaluated here are old. However, all the species evaluated here have a specific set of young essential genes not shared among them. Additionally, these two groups of essential genes are involved with distinct biological functions, suggesting two sets of essential genes: (i) a set of old essential genes common to all the evaluated species, regulating basic cellular functions, and (ii) a set of young essential genes exclusive to each species, which perform specific essential functions in each species.}, } @article {pmid34275698, year = {2022}, author = {Verdonck, R and Legrand, D and Jacob, S and Philippe, H}, title = {Phenotypic plasticity through disposable genetic adaptation in ciliates.}, journal = {Trends in microbiology}, volume = {30}, number = {2}, pages = {120-130}, doi = {10.1016/j.tim.2021.06.007}, pmid = {34275698}, issn = {1878-4380}, mesh = {Adaptation, Physiological/genetics ; Biological Evolution ; *Ciliophora/genetics ; *Paramecium/genetics ; }, abstract = {Ciliates have an extraordinary genetic system in which each cell harbors two distinct kinds of nucleus, a transcriptionally active somatic nucleus and a quiescent germline nucleus. The latter undergoes classical, heritable genetic adaptation, while adaptation of the somatic nucleus is only short-term and thus disposable. The ecological and evolutionary relevance of this nuclear dimorphism have never been well formalized, which is surprising given the long history of using ciliates such as Tetrahymena and Paramecium as model organisms. We present a novel, alternative explanation for ciliate nuclear dimorphism which, we argue, should be considered an instrument of phenotypic plasticity by somatic selection on the level of the ciliate clone, as if it were a diffuse multicellular organism. This viewpoint helps to put some enigmatic aspects of ciliate biology into perspective and presents the diversity of ciliates as a large natural experiment that we can exploit to study phenotypic plasticity and organismality.}, } @article {pmid34268901, year = {2021}, author = {Bik, HM}, title = {Just keep it simple? Benchmarking the accuracy of taxonomy assignment software in metabarcoding studies.}, journal = {Molecular ecology resources}, volume = {21}, number = {7}, pages = {2187-2189}, doi = {10.1111/1755-0998.13473}, pmid = {34268901}, issn = {1755-0998}, mesh = {Animals ; *Benchmarking ; Biodiversity ; *DNA Barcoding, Taxonomic ; Humans ; Phylogeny ; RNA, Ribosomal, 16S ; Software ; }, abstract = {How do you put a name on an unknown piece of DNA? From microbes to mammals, high-throughput metabarcoding studies provide a more objective view of natural communities, overcoming many of the inherent limitations of traditional field surveys and microscopy-based observations (Deiner et al., 2017). Taxonomy assignment is one of the most critical aspects of any metabarcoding study, yet this important bioinformatics task is routinely overlooked. Biodiversity surveys and conservation efforts often depend on formal species inventories: the presence (or absence) of species, and the number of individuals reported across space and time. However, computational workflows applied in eukaryotic metabarcoding studies were originally developed for use with bacterial/archaeal data sets, where microbial researchers rely on one conserved locus (nuclear 16S rRNA) and have access to vast databases with good coverage across most prokaryotic lineages - a situation not mirrored in most multicellular taxa. In this issue of Molecular Ecology Resources, Hleap et al. (2021) carry out an extensive benchmarking exercise focused on taxonomy assignment strategies for eukaryotic metabarcoding studies utilizing the mitochondrial Cytochrome C oxidase I marker gene (COI). They assess the performance and accuracy of software tools representing diverse methodological approaches: from "simple" strategies based on sequence similarity and composition, to model-based phylogenetic and probabilistic classification tools. Contrary to popular assumptions, less complex approaches (BLAST and the QIIME2 feature classifier) consistently outperformed more sophisticated mathematical algorithms and were highly accurate for assigning taxonomy at higher levels (e.g. family). Lower-level assignments at the genus and species level still pose significant challenge for most existing algorithms, and sparse eukaryotic reference databases further limit software performance. This study illuminates current best practices for metabarcoding taxonomy assignments, and underscores the need for community-driven efforts to expand taxonomic and geographic representation in reference DNA barcode databases.}, } @article {pmid34264933, year = {2021}, author = {Loidl, J}, title = {Tetrahymena meiosis: Simple yet ingenious.}, journal = {PLoS genetics}, volume = {17}, number = {7}, pages = {e1009627}, pmid = {34264933}, issn = {1553-7404}, support = {P 31606/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Chromosome Painting ; *Epigenesis, Genetic ; *Meiosis ; Reproduction/*physiology ; Tetrahymena thermophila/*genetics ; }, abstract = {The presence of meiosis, which is a conserved component of sexual reproduction, across organisms from all eukaryotic kingdoms, strongly argues that sex is a primordial feature of eukaryotes. However, extant meiotic structures and processes can vary considerably between organisms. The ciliated protist Tetrahymena thermophila, which diverged from animals, plants, and fungi early in evolution, provides one example of a rather unconventional meiosis. Tetrahymena has a simpler meiosis compared with most other organisms: It lacks both a synaptonemal complex (SC) and specialized meiotic machinery for chromosome cohesion and has a reduced capacity to regulate meiotic recombination. Despite this, it also features several unique mechanisms, including elongation of the nucleus to twice the cell length to promote homologous pairing and prevent recombination between sister chromatids. Comparison of the meiotic programs of Tetrahymena and higher multicellular organisms may reveal how extant meiosis evolved from proto-meiosis.}, } @article {pmid34259548, year = {2021}, author = {Wang, J and Wang, J and Wu, S and Zhang, Z and Li, Y}, title = {Global Geographic Diversity and Distribution of the Myxobacteria.}, journal = {Microbiology spectrum}, volume = {9}, number = {1}, pages = {e0001221}, pmid = {34259548}, issn = {2165-0497}, mesh = {*Biodiversity ; Environmental Microbiology ; Myxococcales/*classification/genetics/*isolation & purification ; Phylogeny ; Soil/chemistry ; Soil Microbiology ; }, abstract = {Bacteria are globally distributed in various environments on earth, but a global view of the geographic diversity and distribution of a single taxon is lacking. The Earth Microbiome Project (EMP) has established a global collection of microbial communities, providing the possibility for such a survey. Myxococcales is a bacterial order with a potent ability to produce diverse natural products and have wide application potential in agriculture, biomedicine, and environmental protection. In this study, through a comparative analysis of the EMP data and public information, we determined that myxobacteria account for 2.34% of the total bacterial operational taxonomic units (OTUs), and are one of the most diverse bacterial groups on Earth. Myxococcales OTUs are globally distributed and prefer nonsaline soil and sediments, followed by saline environments, but rarely appear in host-associated environments. Myxobacteria are among the least-investigated bacterial groups. The presently cultured and genome-sequenced myxobacteria are most likely environmentally widespread and abundant taxa, and account for approximately 10% and 7% of the myxobacterial community (>97% similarity), respectively. This global panoramic view of the geographic distribution and diversity of myxobacteria, as well as their cultured and genome-sequenced information, will enable us to explore these important bioresources more reasonably and efficiently. The diversity and distribution of myxobacteria beyond the EMP data are further discussed. IMPORTANCE The diversity and distribution of bacteria are crucial for our understanding of their ecological importance and application potential. Myxobacteria are fascinating prokaryotes with multicellular behaviors and a potent capacity for producing secondary metabolites, and have a wide range of potential applications. The ecological importance of myxobacteria in major ecosystems is becoming established, but the global geographic diversity and distribution remain unclear. From a global survey we revealed that Myxococcales OTUs are globally distributed and prefer nonsaline soil and sediments, followed by saline environments, but rarely appear in host-associated environments. The global panoramic view of the geographic distribution and diversity of myxobacteria, as well as their cultured and genome-sequenced information, will enable us to explore these important bioresources more reasonably and efficiently.}, } @article {pmid34257365, year = {2021}, author = {Bestová, H and Segrestin, J and von Schwartzenberg, K and Škaloud, P and Lenormand, T and Violle, C}, title = {Biological scaling in green algae: the role of cell size and geometry.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {14425}, pmid = {34257365}, issn = {2045-2322}, mesh = {*Cell Size ; *Chlorophyta ; Models, Biological ; }, abstract = {The Metabolic Scaling Theory (MST), hypothesizes limitations of resource-transport networks in organisms and predicts their optimization into fractal-like structures. As a result, the relationship between population growth rate and body size should follow a cross-species universal quarter-power scaling. However, the universality of metabolic scaling has been challenged, particularly across transitions from bacteria to protists to multicellulars. The population growth rate of unicellulars should be constrained by external diffusion, ruling nutrient uptake, and internal diffusion, operating nutrient distribution. Both constraints intensify with increasing size possibly leading to shifting in the scaling exponent. We focused on unicellular algae Micrasterias. Large size and fractal-like morphology make this species a transitional group between unicellular and multicellular organisms in the evolution of allometry. We tested MST predictions using measurements of growth rate, size, and morphology-related traits. We showed that growth scaling of Micrasterias follows MST predictions, reflecting constraints by internal diffusion transport. Cell fractality and density decrease led to a proportional increase in surface area with body mass relaxing external constraints. Complex allometric optimization enables to maintain quarter-power scaling of population growth rate even with a large unicellular plan. Overall, our findings support fractality as a key factor in the evolution of biological scaling.}, } @article {pmid34244514, year = {2021}, author = {Bernardes, JP and John, U and Woltermann, N and Valiadi, M and Hermann, RJ and Becks, L}, title = {The evolution of convex trade-offs enables the transition towards multicellularity.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4222}, pmid = {34244514}, issn = {2041-1723}, mesh = {Animals ; *Biological Evolution ; Cell Survival/physiology ; Chlamydomonas reinhardtii/*physiology ; *Models, Biological ; Predatory Behavior ; Rotifera/physiology ; }, abstract = {The evolutionary transition towards multicellular life often involves growth in groups of undifferentiated cells followed by differentiation into soma and germ-like cells. Theory predicts that germ soma differentiation is facilitated by a convex trade-off between survival and reproduction. However, this has never been tested and these transitions remain poorly understood at the ecological and genetic level. Here, we study the evolution of cell groups in ten isogenic lines of the unicellular green algae Chlamydomonas reinhardtii with prolonged exposure to a rotifer predator. We confirm that growth in cell groups is heritable and characterized by a convex trade-off curve between reproduction and survival. Identical mutations evolve in all cell group isolates; these are linked to survival and reducing associated cell costs. Overall, we show that just 500 generations of predator selection were sufficient to lead to a convex trade-off and incorporate evolved changes into the prey genome.}, } @article {pmid34236522, year = {2021}, author = {Vigneau, J and Borg, M}, title = {The epigenetic origin of life history transitions in plants and algae.}, journal = {Plant reproduction}, volume = {34}, number = {4}, pages = {267-285}, pmid = {34236522}, issn = {2194-7961}, mesh = {Animals ; Biological Evolution ; *Chlorophyta ; Epigenesis, Genetic ; Germ Cells, Plant ; *Magnoliopsida/genetics ; Phylogeny ; Plants/genetics ; }, abstract = {Plants and algae have a complex life history that transitions between distinct life forms called the sporophyte and the gametophyte. This phenomenon-called the alternation of generations-has fascinated botanists and phycologists for over 170 years. Despite the mesmerizing array of life histories described in plants and algae, we are only now beginning to learn about the molecular mechanisms controlling them and how they evolved. Epigenetic silencing plays an essential role in regulating gene expression during multicellular development in eukaryotes, raising questions about its impact on the life history strategy of plants and algae. Here, we trace the origin and function of epigenetic mechanisms across the plant kingdom, from unicellular green algae through to angiosperms, and attempt to reconstruct the evolutionary steps that influenced life history transitions during plant evolution. Central to this evolutionary scenario is the adaption of epigenetic silencing from a mechanism of genome defense to the repression and control of alternating generations. We extend our discussion beyond the green lineage and highlight the peculiar case of the brown algae. Unlike their unicellular diatom relatives, brown algae lack epigenetic silencing pathways common to animals and plants yet display complex life histories, hinting at the emergence of novel life history controls during stramenopile evolution.}, } @article {pmid34234152, year = {2021}, author = {Mitchell, RN and Gernon, TM and Cox, GM and Nordsvan, AR and Kirscher, U and Xuan, C and Liu, Y and Liu, X and He, X}, title = {Orbital forcing of ice sheets during snowball Earth.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4187}, pmid = {34234152}, issn = {2041-1723}, abstract = {The snowball Earth hypothesis-that a runaway ice-albedo feedback can cause global glaciation-seeks to explain low-latitude glacial deposits, as well as geological anomalies including the re-emergence of banded iron formation and "cap" carbonates. One of the most significant challenges to snowball Earth has been sedimentological cyclicity that has been taken to imply more climate dynamics than expected when the ocean is completely covered in ice. However, recent climate models suggest that as atmospheric CO2 accumulates, the snowball climate system becomes sensitive to orbital forcing. Here we show the presence of nearly all Milankovitch (orbital) cycles preserved in stratified banded iron formation deposited during the Sturtian snowball Earth. These results provide evidence for orbitally forced cyclicity of global ice sheets that resulted in periodic oxidation of ferrous iron. Orbital glacial advance and retreat cycles provide a simple mechanism to reconcile both the sedimentary dynamics and the enigmatic survival of multicellular life during snowball Earth.}, } @article {pmid34221665, year = {2021}, author = {Yan, F and Gunay, G and Valerio, TI and Wang, C and Wilson, JA and Haddad, MS and Watson, M and Connell, MO and Davidson, N and Fung, KM and Acar, H and Tang, Q}, title = {Characterization and quantification of necrotic tissues and morphology in multicellular ovarian cancer tumor spheroids using optical coherence tomography.}, journal = {Biomedical optics express}, volume = {12}, number = {6}, pages = {3352-3371}, pmid = {34221665}, issn = {2156-7085}, support = {P30 CA225520/CA/NCI NIH HHS/United States ; }, abstract = {The three-dimensional (3D) tumor spheroid model is a critical tool for high-throughput ovarian cancer research and anticancer drug development in vitro. However, the 3D structure prevents high-resolution imaging of the inner side of the spheroids. We aim to visualize and characterize 3D morphological and physiological information of the contact multicellular ovarian tumor spheroids growing over time. We intend to further evaluate the distinctive evolutions of the tumor spheroid and necrotic tissue volumes in different cell numbers and determine the most appropriate mathematical model for fitting the growth of tumor spheroids and necrotic tissues. A label-free and noninvasive swept-source optical coherence tomography (SS-OCT) imaging platform was applied to obtain two-dimensional (2D) and 3D morphologies of ovarian tumor spheroids over 18 days. Ovarian tumor spheroids of two different initial cell numbers (5,000- and 50,000- cells) were cultured and imaged (each day) over the time of growth in 18 days. Four mathematical models (Exponential-Linear, Gompertz, logistic, and Boltzmann) were employed to describe the growth kinetics of the tumor spheroids volume and necrotic tissues. Ovarian tumor spheroids have different growth curves with different initial cell numbers and their growths contain different stages with various growth rates over 18 days. The volumes of 50,000-cells spheroids and the corresponding necrotic tissues are larger than that of the 5,000-cells spheroids. The formation of necrotic tissue in 5,000-cells numbers is slower than that in the 50,000-cells ones. Moreover, the Boltzmann model exhibits the best fitting performance for the growth of tumor spheroids and necrotic tissues. Optical coherence tomography (OCT) can serve as a promising imaging modality to visualize and characterize morphological and physiological features of multicellular ovarian tumor spheroids. The Boltzmann model integrating with 3D OCT data of ovarian tumor spheroids provides great potential for high-throughput cancer research in vitro and aiding in drug development.}, } @article {pmid34215938, year = {2021}, author = {Machado, SR and Rodrigues, TM}, title = {Apoplasmic barrier in the extrafloral nectary of Citharexylum myrianthum (Verbenaceae).}, journal = {Planta}, volume = {254}, number = {2}, pages = {19}, pmid = {34215938}, issn = {1432-2048}, support = {401053/2016-4//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 303981/2018-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 308982/2020-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Biological Transport ; Cell Wall ; Plant Nectar ; Trichomes ; *Verbenaceae ; }, abstract = {The cytological changes underlying the formation of an apoplasmic barrier in the multi-layered extrafloral nectaries of Citharexylum myrianthum are compatible with the synthesis, transport and deposition of suberin. In terms of ontogenesis and function, the intermediate layers of these nectaries are homologous with the stalks of nectar-secreting trichomes. Anticlinal cell wall impregnations are common in trichomatic nectaries and their functions as endodermis-like barriers have been discussed because of possible direct effects on the nectary physiology, mainly in the nectar secretion and resorption. However, the cytological events linked to nectary wall impregnations remain little explored. This study documents the ontogenesis and the fine structure of the EFN cells, and cytological events linked to the wall impregnations of multi-layered extrafloral nectaries (EFNs) in Citharexylum myrianthum Cham. (Verbenaceae). EFNs are patelliform, and differentiated into (a) a multicellular foot, which is compound in structure and vascularised with phloem strands, (b) a bi-layered intermediate region with thickened cell walls and (c) a single-layered secretory region with palisade-like cells. EFNs are protodermal in origin, starting with a single protodermal cell and ending with the complex, multi-layered structure. The cell wall impregnations first appear in the very young EFN and increase towards maturity. Lipid patches (assumed to be suberin) are deposited on the inner faces of the primary walls, first along the anticlinal walls and then extend to the periclinal walls. On both walls, plasmodesmata remain apparently intact during the maturation of the EFNs. In the peripheral cytoplasm there are abundant polymorphic plastids, well-developed Golgi bodies often close to rough endoplasmic reticulum profiles, mitochondria and polyribosomes. Cytological events linked to the wall impregnations are consistent with suberin synthesis, transport and deposition. Our findings offer new insights into the structure-properties of specialised nectary cell walls and so should contribute to our knowledge of the physiological and protective roles of this structure in nectar glands.}, } @article {pmid34205034, year = {2021}, author = {Francés-Herrero, E and Juárez-Barber, E and Campo, H and López-Martínez, S and de Miguel-Gómez, L and Faus, A and Pellicer, A and Ferrero, H and Cervelló, I}, title = {Improved Models of Human Endometrial Organoids Based on Hydrogels from Decellularized Endometrium.}, journal = {Journal of personalized medicine}, volume = {11}, number = {6}, pages = {}, pmid = {34205034}, issn = {2075-4426}, support = {PI17/01039//Instituto de Salud Carlos III/ ; CP19/00149//Instituto de Salud Carlos III/ ; FI19/00110//Instituto de Salud Carlos III/ ; CP20/00120//Instituto de Salud Carlos III/ ; FPU18/06327//Spanish Ministry of Science, Innovation and Universities/ ; PROMETEO/2018/137//Regional Valencian Ministry of Education/ ; ACIF/2017/118//Regional Valencian Ministry of Education/ ; }, abstract = {Organoids are three-dimensional (3D) multicellular tissue models that mimic their corresponding in vivo tissue. Successful efforts have derived organoids from primary tissues such as intestine, liver, and pancreas. For human uterine endometrium, the recent generation of 3D structures from primary endometrial cells is inspiring new studies of this important tissue using precise preclinical models. To improve on these 3D models, we decellularized pig endometrium containing tissue-specific extracellular matrix and generated a hydrogel (EndoECM). Next, we derived three lines of human endometrial organoids and cultured them in optimal and suboptimal culture expansion media with or without EndoECM (0.01 mg/mL) as a soluble additive. We characterized the resultant organoids to verify their epithelial origin, long-term chromosomal stability, and stemness properties. Lastly, we determined their proliferation potential under different culture conditions using proliferation rates and immunohistochemical methods. Our results demonstrate the importance of a bioactive environment for the maintenance and proliferation of human endometrial organoids.}, } @article {pmid34204452, year = {2021}, author = {Cricrì, G and Bellucci, L and Montini, G and Collino, F}, title = {Urinary Extracellular Vesicles: Uncovering the Basis of the Pathological Processes in Kidney-Related Diseases.}, journal = {International journal of molecular sciences}, volume = {22}, number = {12}, pages = {}, pmid = {34204452}, issn = {1422-0067}, support = {Grant P-0038//IMPACTsim S.p.A./ ; }, mesh = {Animals ; Biomarkers/*urine ; Cell Communication ; Cell-Derived Microparticles/metabolism ; Chemical Fractionation ; Disease Management ; Disease Susceptibility ; Exosomes/metabolism ; Extracellular Vesicles/*metabolism ; Humans ; Kidney Diseases/diagnosis/etiology/*metabolism/urine ; Liquid Biopsy/methods ; Precision Medicine/methods ; Urinalysis/methods ; }, abstract = {Intercellular communication governs multicellular interactions in complex organisms. A variety of mechanisms exist through which cells can communicate, e.g., cell-cell contact, the release of paracrine/autocrine soluble molecules, or the transfer of extracellular vesicles (EVs). EVs are membrane-surrounded structures released by almost all cell types, acting both nearby and distant from their tissue/organ of origin. In the kidney, EVs are potent intercellular messengers released by all urinary system cells and are involved in cell crosstalk, contributing to physiology and pathogenesis. Moreover, urine is a reservoir of EVs coming from the circulation after crossing the glomerular filtration barrier-or originating in the kidney. Thus, urine represents an alternative source for biomarkers in kidney-related diseases, potentially replacing standard diagnostic techniques, including kidney biopsy. This review will present an overview of EV biogenesis and classification and the leading procedures for isolating EVs from body fluids. Furthermore, their role in intra-nephron communication and their use as a diagnostic tool for precision medicine in kidney-related disorders will be discussed.}, } @article {pmid34199921, year = {2021}, author = {Mikuła, A and Tomaszewicz, W and Dziurka, M and Kaźmierczak, A and Grzyb, M and Sobczak, M and Zdańkowski, P and Rybczyński, J}, title = {The Origin of the Cyathea delgadii Sternb. Somatic Embryos Is Determined by the Developmental State of Donor Tissue and Mutual Balance of Selected Metabolites.}, journal = {Cells}, volume = {10}, number = {6}, pages = {}, pmid = {34199921}, issn = {2073-4409}, mesh = {Cytokinins/*pharmacology ; Ferns/cytology/*metabolism ; *Plant Somatic Embryogenesis Techniques ; }, abstract = {Somatic embryogenesis is the formation of a plant embryo from a cell other than the product of gametic fusion. The need to recognize the determinants of somatic cell fate has prompted investigations on how endogenous factors of donor tissues can determine the pattern of somatic embryo origin. The undertaking of this study was enabled by the newly developed experimental system of somatic embryogenesis of the tree fern Cyathea delgadii Sternb., in which the embryos are produced in hormone-free medium. The contents of 89 endogenous compounds (such as sugars, auxins, cytokinins, gibberellins, stress-related hormones, phenolic acids, polyamines, and amino acids) and cytomorphological features were compared between two types of explants giving rise to somatic embryos of unicellular or multicellular origin. We found that a large content of maltose, 1-kestose, abscisic acid, biologically active gibberellins, and phenolic acids was characteristic for single-cell somatic embryo formation pattern. In contrast, high levels of starch, callose, kinetin riboside, arginine, and ethylene promoted their multicellular origin. Networks for visualization of the relations between studied compounds were constructed based on the data obtained from analyses of a Pearson correlation coefficient heatmap. Our findings present for the first time detailed features of donor tissue that can play an important role in the somatic-to-embryogenic transition and the somatic embryo origin.}, } @article {pmid34181730, year = {2021}, author = {Wu, X and Yan, A and McAdam, SAM and Banks, JA and Zhang, S and Zhou, Y}, title = {Timing of meristem initiation and maintenance determines the morphology of fern gametophytes.}, journal = {Journal of experimental botany}, volume = {72}, number = {20}, pages = {6990-7001}, doi = {10.1093/jxb/erab307}, pmid = {34181730}, issn = {1460-2431}, mesh = {Biological Evolution ; *Ferns ; Germ Cells, Plant ; Meristem ; *Pteridaceae ; }, abstract = {The alternation of generations in land plants occurs between the sporophyte phase and the gametophyte phase. The sporophytes of seed plants develop self-maintained, multicellular meristems, and these meristems determine plant architecture. The gametophytes of seed plants lack meristems and are heterotrophic. In contrast, the gametophytes of seed-free vascular plants, including ferns, are autotrophic and free-living, developing meristems to sustain their independent growth and proliferation. Compared with meristems in the sporophytes of seed plants, the cellular mechanisms underlying meristem development in fern gametophytes remain largely unknown. Here, using confocal time-lapse live imaging and computational segmentation and quantification, we determined different patterns of cell divisions associated with the initiation and proliferation of two distinct types of meristems in gametophytes of two closely related Pteridaceae ferns, Pteris vittata and Ceratopteris richardii. Our results reveal how the simple timing of a switch between two meristems has considerable consequences for the divergent gametophyte morphologies of the two ferns. They further provide evolutionary insight into the function and regulation of gametophyte meristems in seed-free vascular plants.}, } @article {pmid34178962, year = {2021}, author = {Ellis, MA and Dalwadi, MP and Ellis, MJ and Byrne, HM and Waters, SL}, title = {A Systematically Reduced Mathematical Model for Organoid Expansion.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {9}, number = {}, pages = {670186}, pmid = {34178962}, issn = {2296-4185}, abstract = {Organoids are three-dimensional multicellular tissue constructs. When cultured in vitro, they recapitulate the structure, heterogeneity, and function of their in vivo counterparts. As awareness of the multiple uses of organoids has grown, e.g. in drug discovery and personalised medicine, demand has increased for low-cost and efficient methods of producing them in a reproducible manner and at scale. Here we focus on a bioreactor technology for organoid production, which exploits fluid flow to enhance mass transport to and from the organoids. To ensure large numbers of organoids can be grown within the bioreactor in a reproducible manner, nutrient delivery to, and waste product removal from, the organoids must be carefully controlled. We develop a continuum mathematical model to investigate how mass transport within the bioreactor depends on the inlet flow rate and cell seeding density, focusing on the transport of two key metabolites: glucose and lactate. We exploit the thin geometry of the bioreactor to systematically simplify our model. This significantly reduces the computational cost of generating model solutions, and provides insight into the dominant mass transport mechanisms. We test the validity of the reduced models by comparison with simulations of the full model. We then exploit our reduced mathematical model to determine, for a given inlet flow rate and cell seeding density, the evolution of the spatial metabolite distributions throughout the bioreactor. To assess the bioreactor transport characteristics, we introduce metrics quantifying glucose conversion (the ratio between the total amounts of consumed and supplied glucose), the maximum lactate concentration, the proportion of the bioreactor with intolerable lactate concentrations, and the time when intolerable lactate concentrations are first experienced within the bioreactor. We determine the dependence of these metrics on organoid-line characteristics such as proliferation rate and rate of glucose consumption per cell. Finally, for a given organoid line, we determine how the distribution of metabolites and the associated metrics depend on the inlet flow rate. Insights from this study can be used to inform bioreactor operating conditions, ultimately improving the quality and number of bioreactor-expanded organoids.}, } @article {pmid34161405, year = {2021}, author = {Tan, A and Liu, Q and Septiadi, D and Chu, S and Liu, T and Richards, SJ and Rothen-Rutishauser, B and Petri-Fink, A and Gibson, MI and Boyd, BJ}, title = {Understanding selectivity of metabolic labelling and click-targeting in multicellular environments as a route to tissue selective drug delivery.}, journal = {Journal of materials chemistry. B}, volume = {9}, number = {26}, pages = {5365-5373}, doi = {10.1039/d1tb00721a}, pmid = {34161405}, issn = {2050-7518}, support = {BB/M02878X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Cell Line ; Click Chemistry ; Cyclooctanes/chemistry/*metabolism ; *Drug Delivery Systems ; Epithelial Cells/chemistry/metabolism ; Fibroblasts/chemistry/metabolism ; Gold/chemistry/*metabolism ; Hexosamines/chemistry/*metabolism ; Humans ; Metal Nanoparticles/*chemistry ; Molecular Structure ; Particle Size ; Polysaccharides/chemistry/*metabolism ; Surface Properties ; }, abstract = {Cancer cells generally exhibit higher metabolic demands relative to that of normal tissue cells. This offers great possibilities to exploit metabolic glycoengineering in combination with bio-orthogonal chemistry reactions to achieve tumour site-targeted therapeutic delivery. This work addresses the selectivity of metabolic glycan labelling in diseased (i.e., cancer) versus normal cells grown in a multicellular environment. Dibenzocylooctyne (DBCO)-bearing acetylated-d-mannosamine (Ac4ManNDBCO) was synthesised to metabolically label three different types of cell lines originating from the human lung tissues: A549 adenocarcinomic alveolar basal epithelial cells, MeT5A non-cancerous mesothelial cells, and MRC5 non-cancerous fibroblasts. These cell lines displayed different labelling sensitivity, which trended with their doubling time in the following order: A549 ≈ MeT5A > MRC5. The higher metabolic labelling efficiency inherently led to a higher extent of specific binding and accumulation of the clickable N3-conjugated gold nanoparticles (N3-AuNps, core diameter = 30 nm) in the DBCO-glycan modified A549 and MeT5A cells, but to a less prominent effect in MRC5 cells. These findings demonstrate that relative rates of cell metabolism can be exploited using metabolic labelling to recruit nanotherapeutics whilst minimising non-specific targeting of surrounding tissues.}, } @article {pmid34150724, year = {2021}, author = {Martínez-Reina, J and Calvo-Gallego, JL and Pivonka, P}, title = {Combined Effects of Exercise and Denosumab Treatment on Local Failure in Post-menopausal Osteoporosis-Insights from Bone Remodelling Simulations Accounting for Mineralisation and Damage.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {9}, number = {}, pages = {635056}, pmid = {34150724}, issn = {2296-4185}, abstract = {Denosumab has been shown to increase bone mineral density (BMD) and reduce the fracture risk in patients with post-menopausal osteoporosis (PMO). Increase in BMD is linked with an increase in bone matrix mineralisation due to suppression of bone remodelling. However, denosumab anti-resorptive action also leads to an increase in fatigue microdamage, which may ultimately lead to an increased fracture risk. A novel mechanobiological model of bone remodelling was developed to investigate how these counter-acting mechanisms are affected both by exercise and long-term denosumab treatment. This model incorporates Frost's mechanostat feedback, a bone mineralisation algorithm and an evolution law for microdamage accumulation. Mechanical disuse and microdamage were assumed to stimulate RANKL production, which modulates activation frequency of basic multicellular units in bone remodelling. This mechanical feedback mechanism controls removal of excess bone mass and microdamage. Furthermore, a novel measure of bone local failure due to instantaneous overloading was developed. Numerical simulations indicate that trabecular bone volume fraction and bone matrix damage are determined by the respective bone turnover and homeostatic loading conditions. PMO patients treated with the currently WHO-approved dose of denosumab (60 mg administrated every 6 months) exhibit increased BMD, increased bone ash fraction and damage. In untreated patients, BMD will significantly decrease, as will ash fraction; while damage will increase. The model predicted that, depending on the time elapsed between the onset of PMO and the beginning of treatment, BMD slowly converges to the same steady-state value, while damage is low in patients treated soon after the onset of the disease and high in patients having PMO for a longer period. The simulations show that late treatment PMO patients have a significantly higher risk of local failure compared to patients that are treated soon after the onset of the disease. Furthermore, overloading resulted in an increase of BMD, but also in a faster increase of damage, which may consequently promote the risk of fracture, specially in late treatment scenarios. In case of mechanical disuse, the model predicted reduced BMD gains due to denosumab, while no significant change in damage occurred, thus leading to an increased risk of local failure compared to habitual loading.}, } @article {pmid34149674, year = {2021}, author = {Sánchez-Romero, MA and Casadesús, J}, title = {Waddington's Landscapes in the Bacterial World.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {685080}, pmid = {34149674}, issn = {1664-302X}, abstract = {Conrad Waddington's epigenetic landscape, a visual metaphor for the development of multicellular organisms, is appropriate to depict the formation of phenotypic variants of bacterial cells. Examples of bacterial differentiation that result in morphological change have been known for decades. In addition, bacterial populations contain phenotypic cell variants that lack morphological change, and the advent of fluorescent protein technology and single-cell analysis has unveiled scores of examples. Cell-specific gene expression patterns can have a random origin or arise as a programmed event. When phenotypic cell-to-cell differences are heritable, bacterial lineages are formed. The mechanisms that transmit epigenetic states to daughter cells can have strikingly different levels of complexity, from the propagation of simple feedback loops to the formation of complex DNA methylation patterns. Game theory predicts that phenotypic heterogeneity can facilitate bacterial adaptation to hostile or unpredictable environments, serving either as a division of labor or as a bet hedging that anticipates future challenges. Experimental observation confirms the existence of both types of strategies in the bacterial world.}, } @article {pmid34149428, year = {2021}, author = {Földes, A and Sang-Ngoen, T and Kádár, K and Rácz, R and Zsembery, Á and DenBesten, P and Steward, MC and Varga, G}, title = {Three-Dimensional Culture of Ameloblast-Originated HAT-7 Cells for Functional Modeling of Defective Tooth Enamel Formation.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {682654}, pmid = {34149428}, issn = {1663-9812}, support = {R01 DE027971/DE/NIDCR NIH HHS/United States ; }, abstract = {Background: Amelogenesis, the formation of dental enamel, is well understood at the histomorphological level but the underlying molecular mechanisms are poorly characterized. Ameloblasts secrete enamel matrix proteins and Ca[2+], and also regulate extracellular pH as the formation of hydroxyapatite crystals generates large quantities of protons. Genetic or environmental impairment of transport and regulatory processes (e.g. dental fluorosis) leads to the development of enamel defects such as hypomineralization. Aims: Our aims were to optimize the culture conditions for the three-dimensional growth of ameloblast-derived HAT-7 cells and to test the effects of fluoride exposure on HAT-7 spheroid formation. Methods: To generate 3D HAT-7 structures, cells were dispersed and plated within a Matrigel extracellular matrix scaffold and incubated in three different culture media. Spheroid formation was then monitored over a two-week period. Ion transporter and tight-junction protein expression was investigated by RT-qPCR. Intracellular Ca[2+] and pH changes were measured by microfluorometry using the fluorescent dyes fura-2 and BCECF. Results: A combination of Hepato-STIM epithelial cell differentiation medium and Matrigel induced the expansion and formation of 3D HAT-7 spheroids. The cells retained their epithelial cell morphology and continued to express both ameloblast-specific and ion transport-specific marker genes. Furthermore, like two-dimensional HAT-7 monolayers, the HAT-7 spheroids were able to regulate their intracellular pH and to show intracellular calcium responses to extracellular stimulation. Finally, we demonstrated that HAT-7 spheroids may serve as a disease model for studying the effects of fluoride exposure during amelogenesis. Conclusion: In conclusion, HAT-7 cells cultivated within a Matrigel extracellular matrix form three-dimensional, multi-cellular, spheroidal structures that retain their functional capacity for pH regulation and intracellular Ca[2+] signaling. This new 3D model will allow us to gain a better understanding of the molecular mechanisms involved in amelogenesis, not only in health but also in disorders of enamel formation, such as those resulting from fluoride exposure.}, } @article {pmid34147614, year = {2021}, author = {Shang-Guan, XY and Cai, YJ and Xu, HZ and Cheng, X and Zhang, RF and Liu, HX}, title = {A C-type lectin with a single CRD from Onychostoma macrolepis mediates immune recognition against bacterial challenge.}, journal = {Fish & shellfish immunology}, volume = {115}, number = {}, pages = {160-170}, doi = {10.1016/j.fsi.2021.06.007}, pmid = {34147614}, issn = {1095-9947}, mesh = {Aeromonas hydrophila/physiology ; Amino Acid Sequence ; Animals ; Base Sequence ; Cyprinidae/*genetics/*immunology ; Fish Diseases/*immunology ; Fish Proteins/chemistry/genetics/immunology ; Gene Expression Profiling/veterinary ; Gene Expression Regulation/*immunology ; Gram-Negative Bacterial Infections/immunology/veterinary ; Immunity, Innate/*genetics ; Lectins, C-Type/chemistry/*genetics/*immunology ; Phylogeny ; Sequence Alignment/veterinary ; }, abstract = {C-type lectins (CTL) are a large group of pattern-recognition proteins and to play important roles in glycoprotein metabolism, multicellular integration, and immunity. Based on their overall domain structure, they can be classified as different groups that possess different physiological functions. A typical C-type lectin (named as OmLec1) was identified from the fish, Onychostoma macrolepis, an important cultured fish in China. Open reading frame of OmLec1 contains a 570 bp, encoding a protein of 189 amino acids that includes a signal peptide and a single carbohydrate-recognition domain. The phylogenetic analysis showed that OmLec1 could be grouped with C-type lectin from other fish. OmLec1 was expressed in all the tissues in our study, and the expression level was highest in liver. And its relative expression levels were significantly upregulated following infection with Aeromonas hydrophila. The recombinant OmLec1 protein (rOmLec1) could agglutinate some Gram-negative bacteria and Gram-positive bacteria in vitro in the presence of Ca[2+], showing a typical Ca[2+]-dependent carbohydrate-binding protein. Furthermore, rOmLec1 purified from E. coli BL21 (DE3), strongly bound to LPS and PGN, as well as all tested bacteria in a Ca[2+]-dependent manner. These results indicate that OmLec1 plays a central role in the innate immune response and as a pattern recognition receptor that recognizes diverse pathogens among O. macrolepis.}, } @article {pmid34147034, year = {2022}, author = {Caipa Garcia, AL and Arlt, VM and Phillips, DH}, title = {Organoids for toxicology and genetic toxicology: applications with drugs and prospects for environmental carcinogenesis.}, journal = {Mutagenesis}, volume = {37}, number = {2}, pages = {143-154}, pmid = {34147034}, issn = {1464-3804}, support = {MR/N013700/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; C98/A24032/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Carcinogenesis ; Cell Culture Techniques ; Humans ; Mammals ; Models, Biological ; *Organoids ; *Pluripotent Stem Cells ; }, abstract = {Advances in three-dimensional (3D) cell culture technology have led to the development of more biologically and physiologically relevant models to study organ development, disease, toxicology and drug screening. Organoids have been derived from many mammalian tissues, both normal and tumour, from adult stem cells and from pluripotent stem cells. Tissue organoids can retain many of the cell types and much of the structure and function of the organ of origin. Organoids derived from pluripotent stem cells display increased complexity compared with organoids derived from adult stem cells. It has been shown that organoids express many functional xenobiotic-metabolising enzymes including cytochrome P450s (CYPs). This has benefitted the drug development field in facilitating pre-clinical testing of more personalised treatments and in developing large toxicity and efficacy screens for a range of compounds. In the field of environmental and genetic toxicology, treatment of organoids with various compounds has generated responses that are close to those obtained in primary tissues and in vivo models, demonstrating the biological relevance of these in vitro multicellular 3D systems. Toxicological investigations of compounds in different tissue organoids have produced promising results indicating that organoids will refine future studies on the effects of environmental exposures and carcinogenic risk to humans. With further development and standardised procedures, advancing our understanding on the metabolic capabilities of organoids will help to validate their use to investigate the modes of action of environmental carcinogens.}, } @article {pmid34136267, year = {2021}, author = {Kreider, JJ and Pen, I and Kramer, BH}, title = {Antagonistic pleiotropy and the evolution of extraordinary lifespans in eusocial organisms.}, journal = {Evolution letters}, volume = {5}, number = {3}, pages = {178-186}, pmid = {34136267}, issn = {2056-3744}, abstract = {Queens of eusocial species live extraordinarily long compared to their workers. So far, it has been argued that these lifespan divergences are readily explained by the classical evolutionary theory of ageing. As workers predominantly perform risky tasks, such as foraging and nest defense, and queens stay in the well-protected nests, selection against harmful genetic mutations expressed in old age should be weaker in workers than in queens due to caste differences in extrinsic mortality risk, and thus, lead to the evolution of longer queen and shorter worker lifespans. However, these arguments have not been supported by formal models. Here, we present a model for the evolution of caste-specific ageing in social insects, based on Williams' antagonistic pleiotropy theory of ageing. In individual-based simulations, we assume that mutations with antagonistic fitness effects can act within castes, that is, mutations in early life are accompanied by an antagonistic effect acting in later life, or between castes, where antagonistic effects emerge due to caste antagonism or indirect genetic effects between castes. In monogynous social insect species with sterile workers, large lifespan divergences between castes evolved under all different scenarios of antagonistic effects, but regardless of the degree of caste-specific extrinsic mortality. Mutations with antagonistic fitness effects within castes reduced lifespans of both castes, while mutations with between-caste antagonistic effects decreased worker lifespans more than queen lifespans, and consequently increased lifespan divergences. Our results challenge the central explanatory role of extrinsic mortality for caste-specific ageing in eusocial organisms and suggest that antagonistic pleiotropy affects castes differently due to reproductive monopolization by queens, hence, reproductive division of labor. Finally, these findings provide new insights into the evolution of tissue-specific ageing in multicellular organisms in general.}, } @article {pmid34133948, year = {2021}, author = {Puzakov, MV and Puzakova, LV and Cheresiz, SV and Sang, Y}, title = {The IS630/Tc1/mariner transposons in three ctenophore genomes.}, journal = {Molecular phylogenetics and evolution}, volume = {163}, number = {}, pages = {107231}, doi = {10.1016/j.ympev.2021.107231}, pmid = {34133948}, issn = {1095-9513}, mesh = {Animals ; *Ctenophora/genetics ; *Culicidae ; DNA Transposable Elements/genetics ; Phylogeny ; Transposases/genetics ; }, abstract = {Transposable elements (TEs) exert a significant effect on the structure and functioning of the genomes and also serve as a source of the new genes. The study of the TE diversity and evolution in different taxa is indispensable for the fundamental understanding of their roles in the genomes. IS630/Tc1/mariner (ITm) transposable elements represent the most prevalent and diverse group of DNA transposons. In this work, we studied the diversity, evolutionary dynamics and the phylogenetic relationships of the ITm transposons found in three ctenophore species: Mnemiopsis leidyi, Pleurobrachia bachei, Beroe ovata. We identified 29 ITm transposons, seven of which possess the terminal inverted repeats (TIRs) and an intact transposase, and, thus, are, presumably, active. Four other ITm transposons have the features of domesticated TEs. According to the results of the phylogenetic analysis, the ITm transposons of the ctenophores represent five groups - MLE/DD34D, TLE/DD34-38E, mosquito/DD37E, Visiror/DD41D and pogo/DDxD. Pogo/DDxD superfamily turnes out to be the most diverse and prevalent, since it accounts for more than 40% of the TEs identified. The data obtained in this research will fill the gap of knowledge of the diversity and evolution of the ITm transposons in the multicellular genomes and will lay the ground for the study of the TE effects on the evolution of the ctenophores.}, } @article {pmid34127736, year = {2021}, author = {Opazo, JC and Vandewege, MW and Gutierrez, J and Zavala, K and Vargas-Chacoff, L and Morera, FJ and Mardones, GA}, title = {Independent duplications of the Golgi phosphoprotein 3 oncogene in birds.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {12483}, pmid = {34127736}, issn = {2045-2322}, mesh = {Amino Acid Sequence/genetics ; Animals ; Birds/*genetics ; Carcinogenesis/genetics ; *Evolution, Molecular ; Gene Duplication ; Golgi Apparatus/*genetics ; Humans ; Membrane Proteins/*genetics ; Neoplasms/genetics ; Oncogene Proteins/*genetics ; Phosphoproteins/genetics ; Sequence Alignment ; }, abstract = {Golgi phosphoprotein 3 (GOLPH3) was the first reported oncoprotein of the Golgi apparatus. It was identified as an evolutionarily conserved protein upon its discovery about 20 years ago, but its function remains puzzling in normal and cancer cells. The GOLPH3 gene is part of a group of genes that also includes the GOLPH3L gene. Because cancer has deep roots in multicellular evolution, studying the evolution of the GOLPH3 gene family in non-model species represents an opportunity to identify new model systems that could help better understand the biology behind this group of genes. The main goal of this study is to explore the evolution of the GOLPH3 gene family in birds as a starting point to understand the evolutionary history of this oncoprotein. We identified a repertoire of three GOLPH3 genes in birds. We found duplicated copies of the GOLPH3 gene in all main groups of birds other than paleognaths, and a single copy of the GOLPH3L gene. We suggest there were at least three independent origins for GOLPH3 duplicates. Amino acid divergence estimates show that most of the variation is located in the N-terminal region of the protein. Our transcript abundance estimations show that one paralog is highly and ubiquitously expressed, and the others were variable. Our results are an example of the significance of understanding the evolution of the GOLPH3 gene family, especially for unraveling its structural and functional attributes.}, } @article {pmid34120565, year = {2021}, author = {Miguel-Tomé, S and Llinás, RR}, title = {Broadening the definition of a nervous system to better understand the evolution of plants and animals.}, journal = {Plant signaling & behavior}, volume = {16}, number = {10}, pages = {1927562}, pmid = {34120565}, issn = {1559-2324}, mesh = {Animals ; *Biological Evolution ; Electrophysiological Phenomena ; *Nervous System Physiological Phenomena ; *Plant Physiological Phenomena ; Signal Transduction ; Terminology as Topic ; }, abstract = {Most textbook definitions recognize only animals as having nervous systems. However, for the past couple decades, botanists have been meticulously studying long-distance signaling systems in plants, and some researchers have stated that plants have a simple nervous system. Thus, an academic conflict has emerged between those who defend and those who deny the existence of a nervous system in plants. This article analyses that debate, and we propose an alternative to answering yes or no: broadening the definition of a nervous system to include plants. We claim that a definition broader than the current one, which is based only on a phylogenetic viewpoint, would be helpful in obtaining a deeper understanding of how evolution has driven the features of signal generation, transmission and processing in multicellular beings. Also, we propose two possible definitions and exemplify how broader a definition allows for new viewpoints on the evolution of plants, animals and the nervous system.}, } @article {pmid34114607, year = {2021}, author = {Aevarsson, A and Kaczorowska, AK and Adalsteinsson, BT and Ahlqvist, J and Al-Karadaghi, S and Altenbuchner, J and Arsin, H and Átlasson, ÚÁ and Brandt, D and Cichowicz-Cieślak, M and Cornish, KAS and Courtin, J and Dabrowski, S and Dahle, H and Djeffane, S and Dorawa, S and Dusaucy, J and Enault, F and Fedøy, AE and Freitag-Pohl, S and Fridjonsson, OH and Galiez, C and Glomsaker, E and Guérin, M and Gundesø, SE and Gudmundsdóttir, EE and Gudmundsson, H and Håkansson, M and Henke, C and Helleux, A and Henriksen, JR and Hjörleifdóttir, S and Hreggvidsson, GO and Jasilionis, A and Jochheim, A and Jónsdóttir, I and Jónsdóttir, LB and Jurczak-Kurek, A and Kaczorowski, T and Kalinowski, J and Kozlowski, LP and Krupovic, M and Kwiatkowska-Semrau, K and Lanes, O and Lange, J and Lebrat, J and Linares-Pastén, J and Liu, Y and Lorentsen, SA and Lutterman, T and Mas, T and Merré, W and Mirdita, M and Morzywołek, A and Ndela, EO and Karlsson, EN and Olgudóttir, E and Pedersen, C and Perler, F and Pétursdóttir, SK and Plotka, M and Pohl, E and Prangishvili, D and Ray, JL and Reynisson, B and Róbertsdóttir, T and Sandaa, RA and Sczyrba, A and Skírnisdóttir, S and Söding, J and Solstad, T and Steen, IH and Stefánsson, SK and Steinegger, M and Overå, KS and Striberny, B and Svensson, A and Szadkowska, M and Tarrant, EJ and Terzian, P and Tourigny, M and Bergh, TVD and Vanhalst, J and Vincent, J and Vroling, B and Walse, B and Wang, L and Watzlawick, H and Welin, M and Werbowy, O and Wons, E and Zhang, R}, title = {Going to extremes - a metagenomic journey into the dark matter of life.}, journal = {FEMS microbiology letters}, volume = {368}, number = {12}, pages = {}, doi = {10.1093/femsle/fnab067}, pmid = {34114607}, issn = {1574-6968}, mesh = {Bioprospecting/organization & administration ; Computational Biology ; Databases, Genetic ; Europe ; Genome, Viral/*genetics ; Hydrothermal Vents/virology ; *Metagenomics ; Viral Proteins/chemistry/genetics/metabolism ; Virome/genetics ; Viruses/classification/genetics ; }, abstract = {The Virus-X-Viral Metagenomics for Innovation Value-project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of life.}, } @article {pmid34114051, year = {2021}, author = {Márquez-Zacarías, P and Conlin, PL and Tong, K and Pentz, JT and Ratcliff, WC}, title = {Why have aggregative multicellular organisms stayed simple?.}, journal = {Current genetics}, volume = {67}, number = {6}, pages = {871-876}, pmid = {34114051}, issn = {1432-0983}, support = {DEB-1845363//Directorate for Biological Sciences/ ; IOS-1656549//Directorate for Biological Sciences/ ; Packard Foundation Fellowship//David and Lucile Packard Foundation/ ; }, mesh = {*Biological Evolution ; Clonal Evolution ; Eukaryota/cytology/*physiology ; }, abstract = {Multicellularity has evolved numerous times across the tree of life. One of the most fundamental distinctions among multicellular organisms is their developmental mode: whether they stay together during growth and develop clonally, or form a group through the aggregation of free-living cells. The five eukaryotic lineages to independently evolve complex multicellularity (animals, plants, red algae, brown algae, and fungi) all develop clonally. This fact has largely been explained through social evolutionary theory's lens of cooperation and conflict, where cheating within non-clonal groups has the potential to undermine multicellular adaptation. Multicellular organisms that form groups via aggregation could mitigate the costs of cheating by evolving kin recognition systems that prevent the formation of chimeric groups. However, recent work suggests that selection for the ability to aggregate quickly may constrain the evolution of highly specific kin recognition, sowing the seeds for persistent evolutionary conflict. Importantly, other features of aggregative multicellular life cycles may independently act to constrain the evolution of complex multicellularity. All known aggregative multicellular organisms are facultatively multicellular (as opposed to obligately multicellular), allowing unicellular-level adaptation to environmental selection. Because they primarily exist in a unicellular state, it may be difficult for aggregative multicellular organisms to evolve multicellular traits that carry pleiotropic cell-level fitness costs. Thus, even in the absence of social conflict, aggregative multicellular organisms may have limited potential for the evolution of complex multicellularity.}, } @article {pmid34102596, year = {2021}, author = {Amaral-Zettler, LA and Zettler, ER and Mincer, TJ and Klaassen, MA and Gallager, SM}, title = {Biofouling impacts on polyethylene density and sinking in coastal waters: A macro/micro tipping point?.}, journal = {Water research}, volume = {201}, number = {}, pages = {117289}, doi = {10.1016/j.watres.2021.117289}, pmid = {34102596}, issn = {1879-2448}, mesh = {Animals ; *Biofouling ; Environmental Monitoring ; North Sea ; Plastics ; Polyethylene ; *Water Pollutants, Chemical/analysis ; }, abstract = {Biofouling causing an increase in plastic density and sinking is one of the hypotheses to account for the unexpectedly low amount of buoyant plastic debris encountered at the ocean surface. Field surveys show that polyethylene and polypropylene, the two most abundant buoyant plastics, both occur below the surface and in sediments, and experimental studies confirm that biofouling can cause both of these plastics to sink. However, studies quantifying the actual density of fouled plastics are rare, despite the fact that density will determine the transport and eventual fate of plastic in the ocean. Here we investigated the role of microbial biofilms in sinking of polyethylene microplastic and quantified the density changes natural biofouling communities cause in the coastal waters of the North Sea. Molecular data confirmed the variety of bacteria and eukaryotes (including animals and other multicellular organisms) colonizing the plastic over time. Fouling communities increased the density of plastic and caused sinking, and the plastic remained negatively buoyant even during the winter with lower growth rates. Relative surface area alone, however, did not predict whether a plastic piece sank. Due to patchy colonization, fragmentation of sinking pieces may result in smaller pieces regaining buoyancy and returning to the surface. Our results suggest that primarily multicellular organisms cause sinking of plastic pieces with surface area to volume ratios (SA:V) below 100 (generally pieces above a couple hundred micrometers in size), and that this is a "tipping point" at which microbial biofilms become the key players causing sinking of smaller pieces with higher SA:V ratios, including most fibers that are too small for larger (multicellular) organisms to colonize.}, } @article {pmid34102232, year = {2021}, author = {Torday, JS}, title = {Cellular evolution of language.}, journal = {Progress in biophysics and molecular biology}, volume = {167}, number = {}, pages = {140-146}, doi = {10.1016/j.pbiomolbio.2021.05.009}, pmid = {34102232}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Humans ; *Language ; Phenotype ; }, abstract = {The evolutionary origin of language remains unknown despite many efforts to determine the origin of this signature human trait. Based on epigenetic inheritance, the current article hypothesizes that language evolved from cell-cell communication as the basis for generating structure and function embryologically and phylogenetically, as did all physiologic traits. Beginning with lipids forming the first micelle, a vertical integration of the evolved properties of the cell, from multicellular organisms to the introduction of cholesterol into the cell membrane, to the evolution of the peroxisome, the water-land transition and duplication of the βAdrenergic Receptor, the evolution of endothermy, leading to bipedalism, freeing the forelimbs for toolmaking and language, selection pressure for myelinization of the central nervous system to facilitate calcium flux, bespeaks human expression, culminating in the evolution of civilization. This process is epitomized by the Area of Broca as the structural-functional site for both motor control and language formation. The mechanistic interrelationship between motor control and language formation is underscored by the role of FoxP2 gene expression in both bipedalism and language. The effect of endothermy on bipedalism, freeing the forelimbs for toolmaking and language as the vertical integration from Cosmology to Physiology as the basis for language bespeaks human expression.}, } @article {pmid34097041, year = {2021}, author = {Li, Y and Shen, XX and Evans, B and Dunn, CW and Rokas, A}, title = {Rooting the Animal Tree of Life.}, journal = {Molecular biology and evolution}, volume = {38}, number = {10}, pages = {4322-4333}, pmid = {34097041}, issn = {1537-1719}, support = {R56 AI146096/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Ctenophora ; Phylogeny ; }, abstract = {Identifying our most distant animal relatives has emerged as one of the most challenging problems in phylogenetics. This debate has major implications for our understanding of the origin of multicellular animals and of the earliest events in animal evolution, including the origin of the nervous system. Some analyses identify sponges as our most distant animal relatives (Porifera-sister hypothesis), and others identify comb jellies (Ctenophora-sister hypothesis). These analyses vary in many respects, making it difficult to interpret previous tests of these hypotheses. To gain insight into why different studies yield different results, an important next step in the ongoing debate, we systematically test these hypotheses by synthesizing 15 previous phylogenomic studies and performing new standardized analyses under consistent conditions with additional models. We find that Ctenophora-sister is recovered across the full range of examined conditions, and Porifera-sister is recovered in some analyses under narrow conditions when most outgroups are excluded and site-heterogeneous CAT models are used. We additionally find that the number of categories in site-heterogeneous models is sufficient to explain the Porifera-sister results. Furthermore, our cross-validation analyses show CAT models that recover Porifera-sister have hundreds of additional categories and fail to fit significantly better than site-heterogenuous models with far fewer categories. Systematic and standardized testing of diverse phylogenetic models suggests that we should be skeptical of Porifera-sister results both because they are recovered under such narrow conditions and because the models in these conditions fit the data no better than other models that recover Ctenophora-sister.}, } @article {pmid34077702, year = {2021}, author = {Kang, S and Tice, AK and Stairs, CW and Jones, RE and Lahr, DJG and Brown, MW}, title = {The integrin-mediated adhesive complex in the ancestor of animals, fungi, and amoebae.}, journal = {Current biology : CB}, volume = {31}, number = {14}, pages = {3073-3085.e3}, doi = {10.1016/j.cub.2021.04.076}, pmid = {34077702}, issn = {1879-0445}, support = {MOP-142349//CIHR/Canada ; }, mesh = {Amoeba ; Animals ; *Cell Adhesion ; *Eukaryota ; Evolution, Molecular ; Fungi ; *Integrins ; Phylogeny ; }, abstract = {Integrins are transmembrane receptors that activate signal transduction pathways upon extracellular matrix binding. The integrin-mediated adhesive complex (IMAC) mediates various cell physiological processes. Although the IMAC was thought to be specific to animals, in the past ten years these complexes were discovered in other lineages of Obazoa, the group containing animals, fungi, and several microbial eukaryotes. Very recently, many genomes and transcriptomes from Amoebozoa (the eukaryotic supergroup sister to Obazoa), other obazoans, orphan protist lineages, and the eukaryotes' closest prokaryotic relatives, have become available. To increase the resolution of where and when IMAC proteins exist and have emerged, we surveyed these newly available genomes and transcriptomes for the presence of IMAC proteins. Our results highlight that many of these proteins appear to have evolved earlier in eukaryote evolution than previously thought and that co-option of this apparently ancient protein complex was key to the emergence of animal-type multicellularity. The role of the IMACs in amoebozoans is unknown, but they play critical adhesive roles in at least some unicellular organisms.}, } @article {pmid34076889, year = {2021}, author = {Badis, Y and Scornet, D and Harada, M and Caillard, C and Godfroy, O and Raphalen, M and Gachon, CMM and Coelho, SM and Motomura, T and Nagasato, C and Cock, JM}, title = {Targeted CRISPR-Cas9-based gene knockouts in the model brown alga Ectocarpus.}, journal = {The New phytologist}, volume = {231}, number = {5}, pages = {2077-2091}, doi = {10.1111/nph.17525}, pmid = {34076889}, issn = {1469-8137}, mesh = {Animals ; *CRISPR-Cas Systems/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats ; Eukaryota ; Gene Knockout Techniques ; *Phaeophyta/genetics ; }, abstract = {Brown algae are an important group of multicellular eukaryotes, phylogenetically distinct from both the animal and land plant lineages. Ectocarpus has emerged as a model organism to study diverse aspects of brown algal biology, but this system currently lacks an effective reverse genetics methodology to analyse the functions of selected target genes. Here, we report that mutations at specific target sites are generated following the introduction of CRISPR-Cas9 ribonucleoproteins into Ectocarpus cells, using either biolistics or microinjection as the delivery method. Individuals with mutations affecting the ADENINE PHOSPHORIBOSYL TRANSFERASE (APT) gene were isolated following treatment with 2-fluoroadenine, and this selection system was used to isolate individuals in which mutations had been introduced simultaneously at APT and at a second gene. This double mutation approach could potentially be used to isolate mutants affecting any Ectocarpus gene, providing an effective reverse genetics tool for this model organism. The availability of this tool will significantly enhance the utility of Ectocarpus as a model organism for this ecologically and economically important group of marine organisms. Moreover, the methodology described here should be readily transferable to other brown algal species.}, } @article {pmid34069435, year = {2021}, author = {Elders, H and Hennicke, F}, title = {The Pacific Tree-Parasitic Fungus Cyclocybe parasitica Exhibits Monokaryotic Fruiting, Showing Phenotypes Known from Bracket Fungi and from Cyclocybe aegerita.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {7}, number = {5}, pages = {}, pmid = {34069435}, issn = {2309-608X}, support = {HE 7849/3-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Cyclocybe parasitica is a wood-destroying parasitic edible mushroom growing on diverse broad-leafed trees in New Zealand and other Pacific areas. Recent molecular systematics of European Cyclocybe aegerita, a newly delimited Asian phylum and of related species, corroborated the distinction of the chiefly saprobic cultivated edible mushroom C. aegerita from C. parasitica. Here, we show that C. parasitica exhibits a morpho-physiological trait characteristic to its European cousin, i.e., monokaryotic fruiting sensu stricto (basidiome formation without mating). Monokaryotic fruiting structures formed by C. parasitica ICMP 11668-derived monokaryons were categorized into four phenotypes. One of them displays ulcer-like structures previously reported from bracket fungi. Histology of dikaryotic and monokaryotic C. parasitica fruiting structures revealed anatomical commonalities and differences between them, and towards monokaryotic fruiting structures of C. aegerita. Mating experiments with C. parasitica strains representative of each fruiting phenotype identified compatible sibling monokaryons. Given reports on hypothetically monokaryotic basidiome field populations of 'C. aegerita sensu lato', it seems worthwhile to prospectively investigate whether monokaryotic fruiting s.str. occurs in nature. Sampling from such populations including karyotyping, comparative -omics, and competition assays may help to answer this question and provide evidence whether this trait may confer competitive advantages to a species capable of it.}, } @article {pmid34066959, year = {2021}, author = {Miller, WB and Enguita, FJ and Leitão, AL}, title = {Non-Random Genome Editing and Natural Cellular Engineering in Cognition-Based Evolution.}, journal = {Cells}, volume = {10}, number = {5}, pages = {}, pmid = {34066959}, issn = {2073-4409}, mesh = {Animals ; *Biological Evolution ; *Cell Engineering ; Cognition/*physiology ; *Gene Editing ; *Homeostasis ; Humans ; *Selection, Genetic ; }, abstract = {Neo-Darwinism presumes that biological variation is a product of random genetic replication errors and natural selection. Cognition-Based Evolution (CBE) asserts a comprehensive alternative approach to phenotypic variation and the generation of biological novelty. In CBE, evolutionary variation is the product of natural cellular engineering that permits purposive genetic adjustments as cellular problem-solving. CBE upholds that the cornerstone of biology is the intelligent measuring cell. Since all biological information that is available to cells is ambiguous, multicellularity arises from the cellular requirement to maximize the validity of available environmental information. This is best accomplished through collective measurement purposed towards maintaining and optimizing individual cellular states of homeorhesis as dynamic flux that sustains cellular equipoise. The collective action of the multicellular measurement and assessment of information and its collaborative communication is natural cellular engineering. Its yield is linked cellular ecologies and mutualized niche constructions that comprise biofilms and holobionts. In this context, biological variation is the product of collective differential assessment of ambiguous environmental cues by networking intelligent cells. Such concerted action is enabled by non-random natural genomic editing in response to epigenetic impacts and environmental stresses. Random genetic activity can be either constrained or deployed as a 'harnessing of stochasticity'. Therefore, genes are cellular tools. Selection filters cellular solutions to environmental stresses to assure continuous cellular-organismal-environmental complementarity. Since all multicellular eukaryotes are holobionts as vast assemblages of participants of each of the three cellular domains (Prokaryota, Archaea, Eukaryota) and the virome, multicellular variation is necessarily a product of co-engineering among them.}, } @article {pmid34063320, year = {2021}, author = {Mahajan, D and Kancharla, S and Kolli, P and Sharma, AK and Singh, S and Kumar, S and Mohanty, AK and Jena, MK}, title = {Role of Fibulins in Embryonic Stage Development and Their Involvement in Various Diseases.}, journal = {Biomolecules}, volume = {11}, number = {5}, pages = {}, pmid = {34063320}, issn = {2218-273X}, mesh = {Animals ; Calcium-Binding Proteins/genetics/*metabolism ; *Embryonic Development ; Extracellular Matrix/metabolism ; Gene Expression Regulation, Developmental ; Humans ; Neoplasms/*genetics/metabolism ; Protein Isoforms/metabolism ; }, abstract = {The extracellular matrix (ECM) plays an important role in the evolution of early metazoans, as it provides structural and biochemical support to the surrounding cells through the cell-cell and cell-matrix interactions. In multi-cellular organisms, ECM plays a pivotal role in the differentiation of tissues and in the development of organs. Fibulins are ECM glycoproteins, found in a variety of tissues associated with basement membranes, elastic fibers, proteoglycan aggregates, and fibronectin microfibrils. The expression profile of fibulins reveals their role in various developmental processes such as elastogenesis, development of organs during the embryonic stage, tissue remodeling, maintenance of the structural integrity of basement membrane, and elastic fibers, as well as other cellular processes. Apart from this, fibulins are also involved in the progression of human diseases such as cancer, cardiac diseases, congenital disorders, and chronic fibrotic disorders. Different isoforms of fibulins show a dual role of tumor-suppressive and tumor-promoting activities, depending on the cell type and cellular microenvironment in the body. Knockout animal models have provided deep insight into their role in development and diseases. The present review covers details of the structural and expression patterns, along with the role of fibulins in embryonic development and disease progression, with more emphasis on their involvement in the modulation of cancer diseases.}, } @article {pmid34061031, year = {2021}, author = {Kaur, G and Iyer, LM and Burroughs, AM and Aravind, L}, title = {Bacterial death and TRADD-N domains help define novel apoptosis and immunity mechanisms shared by prokaryotes and metazoans.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34061031}, issn = {2050-084X}, support = {F38 LM000084/LM/NLM NIH HHS/United States ; Z01 LM000084/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Apoptosis ; Bacteria/genetics/immunology/*metabolism ; Bacterial Proteins/genetics/immunology/*metabolism ; *Death Domain Superfamily ; Evolution, Molecular ; Genomics ; Host-Pathogen Interactions ; Microbial Viability ; Phylogeny ; Prokaryotic Cells/immunology/*metabolism ; Signal Transduction ; Symbiosis ; TNF Receptor-Associated Death Domain Protein/genetics/immunology/*metabolism ; }, abstract = {Several homologous domains are shared by eukaryotic immunity and programmed cell-death systems and poorly understood bacterial proteins. Recent studies show these to be components of a network of highly regulated systems connecting apoptotic processes to counter-invader immunity, in prokaryotes with a multicellular habit. However, the provenance of key adaptor domains, namely those of the Death-like and TRADD-N superfamilies, a quintessential feature of metazoan apoptotic systems, remained murky. Here, we use sensitive sequence analysis and comparative genomics methods to identify unambiguous bacterial homologs of the Death-like and TRADD-N superfamilies. We show the former to have arisen as part of a radiation of effector-associated α-helical adaptor domains that likely mediate homotypic interactions bringing together diverse effector and signaling domains in predicted bacterial apoptosis- and counter-invader systems. Similarly, we show that the TRADD-N domain defines a key, widespread signaling bridge that links effector deployment to invader-sensing in multicellular bacterial and metazoan counter-invader systems. TRADD-N domains are expanded in aggregating marine invertebrates and point to distinctive diversifying immune strategies probably directed both at RNA and retroviruses and cellular pathogens that might infect such communities. These TRADD-N and Death-like domains helped identify several new bacterial and metazoan counter-invader systems featuring underappreciated, common functional principles: the use of intracellular invader-sensing lectin-like (NPCBM and FGS), transcription elongation GreA/B-C, glycosyltransferase-4 family, inactive NTPase (serving as nucleic acid receptors), and invader-sensing GTPase switch domains. Finally, these findings point to the possibility of multicellular bacteria-stem metazoan symbiosis in the emergence of the immune/apoptotic systems of the latter.}, } @article {pmid34052880, year = {2022}, author = {Fernández, LD and Seppey, CVW and Singer, D and Fournier, B and Tatti, D and Mitchell, EAD and Lara, E}, title = {Niche Conservatism Drives the Elevational Diversity Gradient in Major Groups of Free-Living Soil Unicellular Eukaryotes.}, journal = {Microbial ecology}, volume = {83}, number = {2}, pages = {459-469}, pmid = {34052880}, issn = {1432-184X}, mesh = {Biodiversity ; *Ciliophora/genetics ; Ecosystem ; Phylogeny ; *Soil ; }, abstract = {Ancestral adaptations to tropical-like climates drive most multicellular biogeography and macroecology. Observational studies suggest that this niche conservatism could also be shaping unicellular biogeography and macroecology, although evidence is limited to Acidobacteria and testate amoebae. We tracked the phylogenetic signal of this niche conservatism in far related and functionally contrasted groups of common soil protists (Bacillariophyta, Cercomonadida, Ciliophora, Euglyphida and Kinetoplastida) along a humid but increasingly cold elevational gradient in Switzerland. Protist diversity decreased, and the size of the geographic ranges of taxa increased with elevation and associated decreasing temperature (climate), which is consistent with a macroecological pattern known as the Rapoport effect. Bacillariophyta exhibited phylogenetically overdispersed communities assembled by competitive exclusion of closely related taxa with shared (conserved) niches. By contrast, Cercomonadida, Ciliophora, Euglyphida and Kinetoplastida exhibited phylogenetically clustered communities assembled by habitat filtering, revealing the coexistence of closely related taxa with shared (conserved) adaptations to cope with the humid but temperate to cold climate of the study site. Phylobetadiversity revealed that soil protists exhibit a strong phylogenetic turnover among elevational sites, suggesting that most taxa have evolutionary constraints that prevent them from colonizing the colder and higher sites of the elevation gradient. Our results suggest that evolutionary constraints determine how soil protists colonize climates departing from warm and humid conditions. We posit that these evolutionary constraints are linked to an ancestral adaptation to tropical-like climates, which limits their survival in exceedingly cold sites. This niche conservatism possibly drives their biogeography and macroecology along latitudinal and altitudinal climatic gradients.}, } @article {pmid34050941, year = {2021}, author = {Grandhi, TSP and To, J and Romero, A and Luna, F and Barnes, W and Walker, J and Moran, R and Newlin, R and Miraglia, L and Orth, AP and Horman, SR}, title = {High-throughput CRISPR-mediated 3D enrichment platform for functional interrogation of chemotherapeutic resistance.}, journal = {Biotechnology and bioengineering}, volume = {118}, number = {8}, pages = {3187-3199}, doi = {10.1002/bit.27844}, pmid = {34050941}, issn = {1097-0290}, mesh = {Antineoplastic Agents/*pharmacology ; *Breast Neoplasms/drug therapy/genetics/metabolism ; *CRISPR-Cas Systems ; *Cell Culture Techniques ; Cell Line, Tumor ; *Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor ; Female ; Humans ; Spheroids, Cellular/*metabolism ; *Tumor Microenvironment ; }, abstract = {Cancer is a disease of somatic mutations. These cellular mutations compete to dominate their microenvironment and dictate the disease outcome. While a therapeutic approach to target-specific oncogenic driver mutations helps to manage the disease, subsequent molecular evolution of tumor cells threatens to overtake therapeutic progress. There is a need for rapid, high-throughput, unbiased in vitro discovery screening platforms that capture the native complexities of the tumor and rapidly identify mutations that confer chemotherapeutic drug resistance. Taking the example of the CDK4/6 inhibitor (CDK4/6i) class of drugs, we show that the pooled in vitro CRISPR screening platform enables rapid discovery of drug resistance mutations in a three-dimensional (3D) setting. Gene-edited cancer cell clones assembled into an organotypic multicellular tumor spheroid (MCTS), exposed to CDK4/6i caused selection and enrichment of the most drug-resistant phenotypes, detectable by next-gen sequencing after a span of 28 days. The platform was sufficiently sensitive to enrich for even a single drug-resistant cell within a large, drug-responsive complex 3D tumor spheroid. The genome-wide 3D CRISPR-mediated knockout screen (>18,000 genes) identified several genes whose disruptions conferred resistance to CDK4/6i. Furthermore, multiple novel candidate genes were identified as top hits only in the microphysiological 3D enrichment assay platform and not the conventional 2D assays. Taken together, these findings suggest that including phenotypic 3D resistance profiling in decision trees could improve discovery and reconfirmation of drug resistance mechanisms and afford a platform for exploring noncell autonomous interactions, selection pressures, and clonal competition.}, } @article {pmid34047647, year = {2021}, author = {Sheng, Y and Pan, B and Wei, F and Wang, Y and Gao, S}, title = {Case Study of the Response of N[6]-Methyladenine DNA Modification to Environmental Stressors in the Unicellular Eukaryote Tetrahymena thermophila.}, journal = {mSphere}, volume = {6}, number = {3}, pages = {e0120820}, pmid = {34047647}, issn = {2379-5042}, mesh = {Adenine/*analogs & derivatives/pharmacology ; Epigenesis, Genetic ; Genome, Protozoan ; Methylation ; Protein Processing, Post-Translational ; Stress, Physiological/*drug effects/genetics ; Tetrahymena thermophila/*drug effects/*genetics/metabolism ; }, abstract = {Rediscovered as a potential epigenetic mark, N[6]-methyladenine DNA modification (6mA) was recently reported to be sensitive to environmental stressors in several multicellular eukaryotes. As 6mA distribution and function differ significantly in multicellular and unicellular organisms, whether and how 6mA in unicellular eukaryotes responds to environmental stress remains elusive. Here, we characterized the dynamic changes of 6mA under starvation in the unicellular model organism Tetrahymena thermophila. Single-molecule, real-time (SMRT) sequencing reveals that DNA 6mA levels in starved cells are significantly reduced, especially symmetric 6mA, compared to those in vegetatively growing cells. Despite a global 6mA reduction, the fraction of asymmetric 6mA with a high methylation level was increased, which might be the driving force for stronger nucleosome positioning in starved cells. Starvation affects expression of many metabolism-related genes, the expression level change of which is associated with the amount of 6mA change, thereby linking 6mA with global transcription and starvation adaptation. The reduction of symmetric 6mA and the increase of asymmetric 6mA coincide with the downregulation of AMT1 and upregulation of AMT2 and AMT5, which are supposedly the MT-A70 methyltransferases required for symmetric and asymmetric 6mA, respectively. These results demonstrated that a regulated 6mA response to environmental cues is evolutionarily conserved in eukaryotes. IMPORTANCE Increasing evidence indicated that 6mA could respond to environmental stressors in multicellular eukaryotes. As 6mA distribution and function differ significantly in multicellular and unicellular organisms, whether and how 6mA in unicellular eukaryotes responds to environmental stress remains elusive. In the present work, we characterized the dynamic changes of 6mA under starvation in the unicellular model organism Tetrahymena thermophila. Our results provide insights into how Tetrahymena fine-tunes its 6mA level and composition upon starvation, suggesting that a regulated 6mA response to environmental cues is evolutionarily conserved in eukaryotes.}, } @article {pmid34031540, year = {2021}, author = {Kumari, P and Dahiya, P and Livanos, P and Zergiebel, L and Kölling, M and Poeschl, Y and Stamm, G and Hermann, A and Abel, S and Müller, S and Bürstenbinder, K}, title = {IQ67 DOMAIN proteins facilitate preprophase band formation and division-plane orientation.}, journal = {Nature plants}, volume = {7}, number = {6}, pages = {739-747}, pmid = {34031540}, issn = {2055-0278}, mesh = {Arabidopsis/*cytology/genetics ; Arabidopsis Proteins/genetics/*metabolism ; Dinitrobenzenes ; Gene Expression Regulation, Plant ; Green Fluorescent Proteins/genetics/metabolism ; Microtubules/drug effects/metabolism ; Mutation ; Phylogeny ; Plant Cells/drug effects/metabolism ; Plants, Genetically Modified ; Prophase ; Protein Domains ; Sulfanilamides ; Tobacco/genetics ; Vesicular Transport Proteins/metabolism ; }, abstract = {Spatiotemporal control of cell division is essential for the growth and development of multicellular organisms. In plant cells, proper cell plate insertion during cytokinesis relies on the premitotic establishment of the division plane at the cell cortex. Two plant-specific cytoskeleton arrays, the preprophase band (PPB) and the phragmoplast, play important roles in division-plane orientation and cell plate formation, respectively[1]. Microtubule organization and dynamics and their communication with membranes at the cortex and cell plate are coordinated by multiple, mostly distinct microtubule-associated proteins[2]. How division-plane selection and establishment are linked, however, is still unknown. Here, we report members of the Arabidopsis IQ67 DOMAIN (IQD) family[3] as microtubule-targeted proteins that localize to the PPB and phragmoplast and additionally reside at the cell plate and a polarized cortical region including the cortical division zone (CDZ). IQDs physically interact with PHRAGMOPLAST ORIENTING KINESIN (POK) proteins[4,5] and PLECKSTRIN HOMOLOGY GTPase ACTIVATING (PHGAP) proteins[6], which are core components of the CDZ[1]. The loss of IQD function impairs PPB formation and affects CDZ recruitment of POKs and PHGAPs, resulting in division-plane positioning defects. We propose that IQDs act as cellular scaffolds that facilitate PPB formation and CDZ set-up during symmetric cell division.}, } @article {pmid34026448, year = {2021}, author = {Jiang, S and Li, H and Zeng, Q and Xiao, Z and Zhang, X and Xu, M and He, Y and Wei, Y and Deng, X}, title = {The Dynamic Counterbalance of RAC1-YAP/OB-Cadherin Coordinates Tissue Spreading with Stem Cell Fate Patterning.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {8}, number = {10}, pages = {2004000}, pmid = {34026448}, issn = {2198-3844}, mesh = {Animals ; Cadherins/*metabolism ; Cell Adhesion/physiology ; Cell Differentiation/physiology ; Cell Lineage ; Cell Movement/physiology ; Cells, Cultured ; Mesenchymal Stem Cells/cytology/*metabolism ; Mice ; Models, Animal ; Morphogenesis ; Signal Transduction ; YAP-Signaling Proteins/*metabolism ; rac1 GTP-Binding Protein/*metabolism ; }, abstract = {Tissue spreading represents a key morphogenetic feature of embryonic development and regenerative medicine. However, how molecular signaling orchestrates the spreading dynamics and cell fate commitment of multicellular tissue remains poorly understood. Here, it is demonstrated that the dynamic counterbalance between RAC1-YAP and OB-cadherin plays a key role in coordinating heterogeneous spreading dynamics with distinct cell fate patterning during collective spreading. The spatiotemporal evolution of individual stem cells in spheroids during collective spreading is mapped. Time-lapse cell migratory trajectory analysis combined with in situ cellular biomechanics detection reveal heterogeneous patterns of collective spreading characteristics, where the cells at the periphery are faster, stiffer, and directional compared to those in the center of the spheroid. Single-cell sequencing shows that the divergent spreading result in distinct cell fate patterning, where differentiation, proliferation, and metabolism are enhanced in peripheral cells. Molecular analysis demonstrates that the increased expression of RAC1-YAP rather than OB-cadherin facilitated cell spreading and induced differentiation, and vice versa. The in vivo wound healing experiment confirms the functional role of RAC1-YAP signaling in tissue spreading. These findings shed light on the mechanism of tissue morphogenesis in the progression of development and provide a practical strategy for desirable regenerative therapies.}, } @article {pmid34023299, year = {2021}, author = {Schneider, P and Reece, SE}, title = {The private life of malaria parasites: Strategies for sexual reproduction.}, journal = {Molecular and biochemical parasitology}, volume = {244}, number = {}, pages = {111375}, pmid = {34023299}, issn = {1872-9428}, support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Biological Coevolution ; Culicidae/parasitology ; Erythrocytes/parasitology ; Female ; *Gametogenesis ; Host-Parasite Interactions/genetics ; Humans ; Insect Vectors/parasitology ; Life Cycle Stages/*genetics ; Liver/parasitology ; Malaria/*parasitology/transmission ; Male ; Plasmodium berghei/genetics/*growth & development/metabolism ; Plasmodium chabaudi/genetics/*growth & development/metabolism ; Plasmodium falciparum/genetics/*growth & development/metabolism ; Plasmodium knowlesi/genetics/*growth & development/metabolism ; Reproduction, Asexual ; Sex Ratio ; }, abstract = {Malaria parasites exhibit a complex lifecycle, requiring extensive asexual replication in the liver and blood of the vertebrate host, and in the haemocoel of the insect vector. Yet, they must also undergo a single round of sexual reproduction, which occurs in the vector's midgut upon uptake of a blood meal. Sexual reproduction is obligate for infection of the vector and thus, is essential for onwards transmission to new hosts. Sex in malaria parasites involves several bottlenecks in parasite number, making the stages involved attractive targets for blocking disease transmission. Malaria parasites have evolved a suite of adaptations ("strategies") to maximise the success of sexual reproduction and transmission, which could undermine transmission-blocking interventions. Yet, understanding parasite strategies may also reveal novel opportunities for such interventions. Here, we outline how evolutionary and ecological theories, developed to explain reproductive strategies in multicellular taxa, can be applied to explain two reproductive strategies (conversion rate and sex ratio) expressed by malaria parasites within the vertebrate host.}, } @article {pmid34020820, year = {2021}, author = {Tanay, A and Sebé-Pedrós, A}, title = {Evolutionary cell type mapping with single-cell genomics.}, journal = {Trends in genetics : TIG}, volume = {37}, number = {10}, pages = {919-932}, doi = {10.1016/j.tig.2021.04.008}, pmid = {34020820}, issn = {0168-9525}, mesh = {Animals ; Cells/*classification/*metabolism ; *Evolution, Molecular ; Genome/*genetics ; *Genomics ; Humans ; Organ Specificity ; *Single-Cell Analysis ; }, abstract = {A fundamental characteristic of animal multicellularity is the spatial coexistence of functionally specialized cell types that are all encoded by a single genome sequence. Cell type transcriptional programs are deployed and maintained by regulatory mechanisms that control the asymmetric, differential access to genomic information in each cell. This genome regulation ultimately results in specific cellular phenotypes. However, the emergence, diversity, and evolutionary dynamics of animal cell types remain almost completely unexplored beyond a few species. Single-cell genomics is emerging as a powerful tool to build comprehensive catalogs of cell types and their associated gene regulatory programs in non-traditional model species. We review the current state of sampling efforts across the animal tree of life and challenges ahead for the comparative study of cell type programs. We also discuss how the phylogenetic integration of cell atlases can lead to the development of models of cell type evolution and a phylogenetic taxonomy of cells.}, } @article {pmid34007033, year = {2021}, author = {Maier, BA and Kiefer, P and Field, CM and Hemmerle, L and Bortfeld-Miller, M and Emmenegger, B and Schäfer, M and Pfeilmeier, S and Sunagawa, S and Vogel, CM and Vorholt, JA}, title = {A general non-self response as part of plant immunity.}, journal = {Nature plants}, volume = {7}, number = {5}, pages = {696-705}, pmid = {34007033}, issn = {2055-0278}, support = {668991/ERC_/European Research Council/International ; }, mesh = {Arabidopsis/*immunology/microbiology/physiology ; Bacteria/genetics/immunology ; Gene Expression Regulation, Plant ; Genes, Plant/immunology/physiology ; Metabolome ; Phylogeny ; Plant Diseases/immunology/microbiology ; Plant Immunity/genetics/physiology ; Secondary Metabolism ; Tryptophan/metabolism ; }, abstract = {Plants, like other multicellular lifeforms, are colonized by microorganisms. How plants respond to their microbiota is currently not well understood. We used a phylogenetically diverse set of 39 endogenous bacterial strains from Arabidopsis thaliana leaves to assess host transcriptional and metabolic adaptations to bacterial encounters. We identified a molecular response, which we termed the general non-self response (GNSR) that involves the expression of a core set of 24 genes. The GNSR genes are not only consistently induced by the presence of most strains, they also comprise the most differentially regulated genes across treatments and are predictive of a hierarchical transcriptional reprogramming beyond the GNSR. Using a complementary untargeted metabolomics approach we link the GNSR to the tryptophan-derived secondary metabolism, highlighting the importance of small molecules in plant-microbe interactions. We demonstrate that several of the GNSR genes are required for resistance against the bacterial pathogen Pseudomonas syringae. Our results suggest that the GNSR constitutes a defence adaptation strategy that is consistently elicited by diverse strains from various phyla, contributes to host protection and involves secondary metabolism.}, } @article {pmid33990594, year = {2021}, author = {Bozdag, GO and Libby, E and Pineau, R and Reinhard, CT and Ratcliff, WC}, title = {Oxygen suppression of macroscopic multicellularity.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2838}, pmid = {33990594}, issn = {2041-1723}, mesh = {Aerobiosis ; Anaerobiosis ; *Biological Evolution ; Biophysical Phenomena ; DNA-Binding Proteins/genetics ; Directed Molecular Evolution ; Eukaryotic Cells/*cytology/*metabolism ; Gene Deletion ; Genetic Engineering ; *Models, Biological ; Oxygen/*metabolism ; Saccharomyces cerevisiae/*cytology/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Selection, Genetic ; Synthetic Biology ; Transcription Factors/genetics ; }, abstract = {Atmospheric oxygen is thought to have played a vital role in the evolution of large, complex multicellular organisms. Challenging the prevailing theory, we show that the transition from an anaerobic to an aerobic world can strongly suppress the evolution of macroscopic multicellularity. Here we select for increased size in multicellular 'snowflake' yeast across a range of metabolically-available O2 levels. While yeast under anaerobic and high-O2 conditions evolved to be considerably larger, intermediate O2 constrained the evolution of large size. Through sequencing and synthetic strain construction, we confirm that this is due to O2-mediated divergent selection acting on organism size. We show via mathematical modeling that our results stem from nearly universal evolutionary and biophysical trade-offs, and thus should apply broadly. These results highlight the fact that oxygen is a double-edged sword: while it provides significant metabolic advantages, selection for efficient use of this resource may paradoxically suppress the evolution of macroscopic multicellular organisms.}, } @article {pmid33988501, year = {2021}, author = {Lu, YX and Regan, JC and Eßer, J and Drews, LF and Weinseis, T and Stinn, J and Hahn, O and Miller, RA and Grönke, S and Partridge, L}, title = {A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33988501}, issn = {2050-084X}, support = {P30 AG024824/AG/NIA NIH HHS/United States ; P40 OD018537/OD/NIH HHS/United States ; U01 AG022303/AG/NIA NIH HHS/United States ; U19 AG023122/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*drug effects/metabolism ; Animals ; *Autophagy ; Chromatin/metabolism ; Drosophila melanogaster ; Eukaryotic Initiation Factor-3/metabolism ; Female ; Gene Expression Regulation ; Histones/genetics/*metabolism ; Intestines ; Mechanistic Target of Rapamycin Complex 1/genetics/*metabolism ; Mice ; Sirolimus/pharmacology ; }, abstract = {Age-related changes to histone levels are seen in many species. However, it is unclear whether changes to histone expression could be exploited to ameliorate the effects of ageing in multicellular organisms. Here we show that inhibition of mTORC1 by the lifespan-extending drug rapamycin increases expression of histones H3 and H4 post-transcriptionally through eIF3-mediated translation. Elevated expression of H3/H4 in intestinal enterocytes in Drosophila alters chromatin organisation, induces intestinal autophagy through transcriptional regulation, and prevents age-related decline in the intestine. Importantly, it also mediates rapamycin-induced longevity and intestinal health. Histones H3/H4 regulate expression of an autophagy cargo adaptor Bchs (WDFY3 in mammals), increased expression of which in enterocytes mediates increased H3/H4-dependent healthy longevity. In mice, rapamycin treatment increases expression of histone proteins and Wdfy3 transcription, and alters chromatin organisation in the small intestine, suggesting that the mTORC1-histone axis is at least partially conserved in mammals and may offer new targets for anti-ageing interventions.}, } @article {pmid33984158, year = {2021}, author = {Lineweaver, CH and Bussey, KJ and Blackburn, AC and Davies, PCW}, title = {Cancer progression as a sequence of atavistic reversions.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {7}, pages = {e2000305}, pmid = {33984158}, issn = {1521-1878}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; U54-CA143682/CA/NCI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Eukaryota ; Eukaryotic Cells ; Humans ; *Neoplasms/genetics ; Phenotype ; }, abstract = {It has long been recognized that cancer onset and progression represent a type of reversion to an ancestral quasi-unicellular phenotype. This general concept has been refined into the atavistic model of cancer that attempts to provide a quantitative analysis and testable predictions based on genomic data. Over the past decade, support for the multicellular-to-unicellular reversion predicted by the atavism model has come from phylostratigraphy. Here, we propose that cancer onset and progression involve more than a one-off multicellular-to-unicellular reversion, and are better described as a series of reversionary transitions. We make new predictions based on the chronology of the unicellular-eukaryote-to-multicellular-eukaryote transition. We also make new predictions based on three other evolutionary transitions that occurred in our lineage: eukaryogenesis, oxidative phosphorylation and the transition to adaptive immunity. We propose several modifications to current phylostratigraphy to improve age resolution to test these predictions. Also see the video abstract here: https://youtu.be/3unEu5JYJrQ.}, } @article {pmid33983920, year = {2021}, author = {van Gestel, J and Wagner, A}, title = {Cryptic surface-associated multicellularity emerges through cell adhesion and its regulation.}, journal = {PLoS biology}, volume = {19}, number = {5}, pages = {e3001250}, pmid = {33983920}, issn = {1545-7885}, mesh = {Animals ; Bacteria/metabolism ; Bacterial Adhesion/*physiology ; Biological Evolution ; Cell Adhesion/*physiology ; Cell Communication/physiology ; Cell Polarity/physiology ; Evolution, Molecular ; Fungi/metabolism ; Humans ; }, abstract = {The repeated evolution of multicellularity led to a wide diversity of organisms, many of which are sessile, including land plants, many fungi, and colonial animals. Sessile organisms adhere to a surface for most of their lives, where they grow and compete for space. Despite the prevalence of surface-associated multicellularity, little is known about its evolutionary origin. Here, we introduce a novel theoretical approach, based on spatial lineage tracking of cells, to study this origin. We show that multicellularity can rapidly evolve from two widespread cellular properties: cell adhesion and the regulatory control of adhesion. By evolving adhesion, cells attach to a surface, where they spontaneously give rise to primitive cell collectives that differ in size, life span, and mode of propagation. Selection in favor of large collectives increases the fraction of adhesive cells until a surface becomes fully occupied. Through kin recognition, collectives then evolve a central-peripheral polarity in cell adhesion that supports a division of labor between cells and profoundly impacts growth. Despite this spatial organization, nascent collectives remain cryptic, lack well-defined boundaries, and would require experimental lineage tracking technologies for their identification. Our results suggest that cryptic multicellularity could readily evolve and originate well before multicellular individuals become morphologically evident.}, } @article {pmid33979602, year = {2021}, author = {Joy, DA and Libby, ARG and McDevitt, TC}, title = {Deep neural net tracking of human pluripotent stem cells reveals intrinsic behaviors directing morphogenesis.}, journal = {Stem cell reports}, volume = {16}, number = {5}, pages = {1317-1330}, pmid = {33979602}, issn = {2213-6711}, support = {T32 HD007470/HD/NICHD NIH HHS/United States ; }, mesh = {Bone Morphogenetic Protein 4/pharmacology ; Cell Count ; Cell Differentiation/drug effects ; Cell Lineage/drug effects ; Cell Movement/drug effects ; Cell Tracking ; Cells, Cultured ; Humans ; Image Processing, Computer-Assisted ; Induced Pluripotent Stem Cells/*cytology/drug effects ; *Morphogenesis/drug effects ; *Neural Networks, Computer ; Smad Proteins/metabolism ; }, abstract = {Lineage tracing is a powerful tool in developmental biology to interrogate the evolution of tissue formation, but the dense, three-dimensional nature of tissue limits the assembly of individual cell trajectories into complete reconstructions of development. Human induced pluripotent stem cells (hiPSCs) can recapitulate aspects of developmental processes, providing an in vitro platform to assess the dynamic collective behaviors directing tissue morphogenesis. Here, we trained an ensemble of neural networks to track individual hiPSCs in time-lapse microscopy, generating longitudinal measures of cell and cellular neighborhood properties on timescales from minutes to days. Our analysis reveals that, while individual cell parameters are not strongly affected by pluripotency maintenance conditions or morphogenic cues, regional changes in cell behavior predict cell fate and colony organization. By generating complete multicellular reconstructions of hiPSC behavior, our tracking pipeline enables fine-grained understanding of morphogenesis by elucidating the role of regional behavior in early tissue formation.}, } @article {pmid33972551, year = {2021}, author = {Tsutsui, K and Machida, H and Nakagawa, A and Ahn, K and Morita, R and Sekiguchi, K and Miner, JH and Fujiwara, H}, title = {Mapping the molecular and structural specialization of the skin basement membrane for inter-tissue interactions.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2577}, pmid = {33972551}, issn = {2041-1723}, support = {R01 DK078314/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Basement Membrane/*cytology/metabolism/ultrastructure ; Epithelial Cells/metabolism ; Extracellular Matrix/genetics/*metabolism ; Female ; Fibroblasts/metabolism ; Hair Follicle/*metabolism ; Immunohistochemistry ; Laminin/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Electron, Transmission ; Multigene Family ; Muscle Cells/metabolism ; Neurons/metabolism ; Single-Cell Analysis ; Transcriptome/*genetics ; }, abstract = {Inter-tissue interaction is fundamental to multicellularity. Although the basement membrane (BM) is located at tissue interfaces, its mode of action in inter-tissue interactions remains poorly understood, mainly because the molecular and structural details of the BM at distinct inter-tissue interfaces remain unclear. By combining quantitative transcriptomics and immunohistochemistry, we systematically identify the cellular origin, molecular identity and tissue distribution of extracellular matrix molecules in mouse hair follicles, and reveal that BM composition and architecture are exquisitely specialized for distinct inter-tissue interactions, including epithelial-fibroblast, epithelial-muscle and epithelial-nerve interactions. The epithelial-fibroblast interface, namely, hair germ-dermal papilla interface, makes asymmetrically organized side-specific heterogeneity in the BM, defined by the newly characterized interface, hook and mesh BMs. One component of these BMs, laminin α5, is required for hair cycle regulation and hair germ-dermal papilla anchoring. Our study highlights the significance of BM heterogeneity in distinct inter-tissue interactions.}, } @article {pmid33961843, year = {2021}, author = {Levin, M}, title = {Bioelectrical approaches to cancer as a problem of the scaling of the cellular self.}, journal = {Progress in biophysics and molecular biology}, volume = {165}, number = {}, pages = {102-113}, doi = {10.1016/j.pbiomolbio.2021.04.007}, pmid = {33961843}, issn = {1873-1732}, mesh = {Electrophysiological Phenomena ; Humans ; Membrane Potentials ; Morphogenesis ; *Neoplasms ; *Signal Transduction ; }, abstract = {One lens with which to understand the complex phenomenon of cancer is that of developmental biology. Cancer is the inevitable consequence of a breakdown of the communication that enables individual cells to join into computational networks that work towards large-scale, morphogenetic goals instead of more primitive, unicellular objectives. This perspective suggests that cancer may be a physiological disorder, not necessarily due to problems with the genetically-specified protein hardware. One aspect of morphogenetic coordination is bioelectric signaling, and indeed an abnormal bioelectric signature non-invasively reveals the site of incipient tumors in amphibian models. Functionally, a disruption of resting potential states triggers metastatic melanoma phenotypes in embryos with no genetic defects or carcinogen exposure. Conversely, optogenetic or molecular-biological modulation of bioelectric states can override powerful oncogenic mutations and prevent or normalize tumors. The bioelectrically-mediated information flows that harness cells toward body-level anatomical outcomes represent a very attractive and tractable endogenous control system, which is being targeted by emerging approaches to cancer.}, } @article {pmid33952585, year = {2021}, author = {Russo, M and Sogari, A and Bardelli, A}, title = {Adaptive Evolution: How Bacteria and Cancer Cells Survive Stressful Conditions and Drug Treatment.}, journal = {Cancer discovery}, volume = {11}, number = {8}, pages = {1886-1895}, doi = {10.1158/2159-8290.CD-20-1588}, pmid = {33952585}, issn = {2159-8290}, mesh = {*Bacteria ; *Biological Evolution ; *Homeostasis ; Humans ; *Neoplasms ; }, abstract = {Cancer is characterized by loss of the regulatory mechanisms that preserve homeostasis in multicellular organisms, such as controlled proliferation, cell-cell adhesion, and tissue differentiation. The breakdown of multicellularity rules is accompanied by activation of "selfish," unicellular-like life features, which are linked to the increased adaptability to environmental changes displayed by cancer cells. Mechanisms of stress response, resembling those observed in unicellular organisms, are actively exploited by mammalian cancer cells to boost genetic diversity and increase chances of survival under unfavorable conditions, such as lack of oxygen/nutrients or exposure to drugs. Unicellular organisms under stressful conditions (e.g., antibiotic treatment) stop replicating or slowly divide and transiently increase their mutation rates to foster diversity, a process known as adaptive mutability. Analogously, tumor cells exposed to drugs enter a persister phenotype and can reduce DNA replication fidelity, which in turn fosters genetic diversity. The implications of adaptive evolution are of relevance to understand resistance to anticancer therapies.}, } @article {pmid33947812, year = {2021}, author = {Hartl, B and Hübl, M and Kahl, G and Zöttl, A}, title = {Microswimmers learning chemotaxis with genetic algorithms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {19}, pages = {}, pmid = {33947812}, issn = {1091-6490}, mesh = {Algorithms ; Animals ; Caenorhabditis elegans/physiology ; Chemotaxis/*genetics/*physiology ; Computer Simulation ; Flagella/physiology ; Learning/*physiology ; Machine Learning ; Models, Biological ; Motion ; Neural Networks, Computer ; Swimming/*physiology ; }, abstract = {Various microorganisms and some mammalian cells are able to swim in viscous fluids by performing nonreciprocal body deformations, such as rotating attached flagella or by distorting their entire body. In order to perform chemotaxis (i.e., to move toward and to stay at high concentrations of nutrients), they adapt their swimming gaits in a nontrivial manner. Here, we propose a computational model, which features autonomous shape adaptation of microswimmers moving in one dimension toward high field concentrations. As an internal decision-making machinery, we use artificial neural networks, which control the motion of the microswimmer. We present two methods to measure chemical gradients, spatial and temporal sensing, as known for swimming mammalian cells and bacteria, respectively. Using the genetic algorithm NeuroEvolution of Augmenting Topologies, surprisingly simple neural networks evolve. These networks control the shape deformations of the microswimmers and allow them to navigate in static and complex time-dependent chemical environments. By introducing noisy signal transmission in the neural network, the well-known biased run-and-tumble motion emerges. Our work demonstrates that the evolution of a simple and interpretable internal decision-making machinery coupled to the environment allows navigation in diverse chemical landscapes. These findings are of relevance for intracellular biochemical sensing mechanisms of single cells or for the simple nervous system of small multicellular organisms such as Caenorhabditis elegans.}, } @article {pmid33947439, year = {2021}, author = {Wang, SY and Pollina, EA and Wang, IH and Pino, LK and Bushnell, HL and Takashima, K and Fritsche, C and Sabin, G and Garcia, BA and Greer, PL and Greer, EL}, title = {Role of epigenetics in unicellular to multicellular transition in Dictyostelium.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {134}, pmid = {33947439}, issn = {1474-760X}, support = {DP2 AG067490/AG/NIA NIH HHS/United States ; R00 AG043550/AG/NIA NIH HHS/United States ; R01 GM110174/GM/NIGMS NIH HHS/United States ; DP2 AG055947/AG/NIA NIH HHS/United States ; T32 CA009140/CA/NCI NIH HHS/United States ; K99 AG064042/AG/NIA NIH HHS/United States ; }, mesh = {Acetylation ; Animals ; Caenorhabditis elegans/cytology ; Chromatin/metabolism ; Dictyostelium/*cytology/*genetics ; *Epigenesis, Genetic ; Gene Expression Profiling ; Histones/metabolism ; Methylation ; Schizosaccharomyces/cytology ; Transcription Factors/metabolism ; }, abstract = {BACKGROUND: The evolution of multicellularity is a critical event that remains incompletely understood. We use the social amoeba, Dictyostelium discoideum, one of the rare organisms that readily transits back and forth between both unicellular and multicellular stages, to examine the role of epigenetics in regulating multicellularity.

RESULTS: While transitioning to multicellular states, patterns of H3K4 methylation and H3K27 acetylation significantly change. By combining transcriptomics, epigenomics, chromatin accessibility, and orthologous gene analyses with other unicellular and multicellular organisms, we identify 52 conserved genes, which are specifically accessible and expressed during multicellular states. We validated that four of these genes, including the H3K27 deacetylase hdaD, are necessary and that an SMC-like gene, smcl1, is sufficient for multicellularity in Dictyostelium.

CONCLUSIONS: These results highlight the importance of epigenetics in reorganizing chromatin architecture to facilitate multicellularity in Dictyostelium discoideum and raise exciting possibilities about the role of epigenetics in the evolution of multicellularity more broadly.}, } @article {pmid33947322, year = {2021}, author = {Orban, A and Weber, A and Herzog, R and Hennicke, F and Rühl, M}, title = {Transcriptome of different fruiting stages in the cultivated mushroom Cyclocybe aegerita suggests a complex regulation of fruiting and reveals enzymes putatively involved in fungal oxylipin biosynthesis.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {324}, pmid = {33947322}, issn = {1471-2164}, mesh = {*Agaricales/genetics ; Agrocybe ; Fruiting Bodies, Fungal/genetics ; Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; Oxylipins ; Prospective Studies ; *Transcriptome ; }, abstract = {BACKGROUND: Cyclocybe aegerita (syn. Agrocybe aegerita) is a commercially cultivated mushroom. Its archetypal agaric morphology and its ability to undergo its whole life cycle under laboratory conditions makes this fungus a well-suited model for studying fruiting body (basidiome, basidiocarp) development. To elucidate the so far barely understood biosynthesis of fungal volatiles, alterations in the transcriptome during different developmental stages of C. aegerita were analyzed and combined with changes in the volatile profile during its different fruiting stages.

RESULTS: A transcriptomic study at seven points in time during fruiting body development of C. aegerita with seven mycelial and five fruiting body stages was conducted. Differential gene expression was observed for genes involved in fungal fruiting body formation showing interesting transcriptional patterns and correlations of these fruiting-related genes with the developmental stages. Combining transcriptome and volatilome data, enzymes putatively involved in the biosynthesis of C8 oxylipins in C. aegerita including lipoxygenases (LOXs), dioxygenases (DOXs), hydroperoxide lyases (HPLs), alcohol dehydrogenases (ADHs) and ene-reductases could be identified. Furthermore, we were able to localize the mycelium as the main source for sesquiterpenes predominant during sporulation in the headspace of C. aegerita cultures. In contrast, changes in the C8 profile detected in late stages of development are probably due to the activity of enzymes located in the fruiting bodies.

CONCLUSIONS: In this study, the combination of volatilome and transcriptome data of C. aegerita revealed interesting candidates both for functional genetics-based analysis of fruiting-related genes and for prospective enzyme characterization studies to further elucidate the so far barely understood biosynthesis of fungal C8 oxylipins.}, } @article {pmid33924996, year = {2021}, author = {Isaksson, H and Conlin, PL and Kerr, B and Ratcliff, WC and Libby, E}, title = {The Consequences of Budding versus Binary Fission on Adaptation and Aging in Primitive Multicellularity.}, journal = {Genes}, volume = {12}, number = {5}, pages = {}, pmid = {33924996}, issn = {2073-4425}, mesh = {*Adaptation, Physiological ; Aging/*genetics ; Animals ; *Cell Division ; Cellular Senescence ; *Models, Theoretical ; Mutation ; }, abstract = {Early multicellular organisms must gain adaptations to outcompete their unicellular ancestors, as well as other multicellular lineages. The tempo and mode of multicellular adaptation is influenced by many factors including the traits of individual cells. We consider how a fundamental aspect of cells, whether they reproduce via binary fission or budding, can affect the rate of adaptation in primitive multicellularity. We use mathematical models to study the spread of beneficial, growth rate mutations in unicellular populations and populations of multicellular filaments reproducing via binary fission or budding. Comparing populations once they reach carrying capacity, we find that the spread of mutations in multicellular budding populations is qualitatively distinct from the other populations and in general slower. Since budding and binary fission distribute age-accumulated damage differently, we consider the effects of cellular senescence. When growth rate decreases with cell age, we find that beneficial mutations can spread significantly faster in a multicellular budding population than its corresponding unicellular population or a population reproducing via binary fission. Our results demonstrate that basic aspects of the cell cycle can give rise to different rates of adaptation in multicellular organisms.}, } @article {pmid33923657, year = {2021}, author = {Romanova, MA and Maksimova, AI and Pawlowski, K and Voitsekhovskaja, OV}, title = {YABBY Genes in the Development and Evolution of Land Plants.}, journal = {International journal of molecular sciences}, volume = {22}, number = {8}, pages = {}, pmid = {33923657}, issn = {1422-0067}, support = {#13-04-02000, #14-04-01397, #17-04-00837//Russian Foundation for Basic Research/ ; #075-15-2020-933//the Ministry of Science and Higher Education of the Russian Federation/ ; }, mesh = {*Evolution, Molecular ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Magnoliopsida/*genetics/growth & development/metabolism ; Plant Proteins/chemistry/*genetics/metabolism ; Transcription Factors/chemistry/*genetics/metabolism ; }, abstract = {Mounting evidence from genomic and transcriptomic studies suggests that most genetic networks regulating the morphogenesis of land plant sporophytes were co-opted and modified from those already present in streptophyte algae and gametophytes of bryophytes sensu lato. However, thus far, no candidate genes have been identified that could be responsible for "planation", a conversion from a three-dimensional to a two-dimensional growth pattern. According to the telome theory, "planation" was required for the genesis of the leaf blade in the course of leaf evolution. The key transcription factors responsible for leaf blade development in angiosperms are YABBY proteins, which until recently were thought to be unique for seed plants. Yet, identification of a YABBY homologue in a green alga and the recent findings of YABBY homologues in lycophytes and hornworts suggest that YABBY proteins were already present in the last common ancestor of land plants. Thus, these transcriptional factors could have been involved in "planation", which fosters our understanding of the origin of leaves. Here, we summarise the current data on functions of YABBY proteins in the vegetative and reproductive development of diverse angiosperms and gymnosperms as well as in the development of lycophytes. Furthermore, we discuss a putative role of YABBY proteins in the genesis of multicellular shoot apical meristems and in the evolution of leaves in early divergent terrestrial plants.}, } @article {pmid33911080, year = {2021}, author = {Moreira, D and Zivanovic, Y and López-Archilla, AI and Iniesto, M and López-García, P}, title = {Reductive evolution and unique predatory mode in the CPR bacterium Vampirococcus lugosii.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2454}, pmid = {33911080}, issn = {2041-1723}, mesh = {Bacteria/*classification/*genetics/metabolism ; Bacterial Physiological Phenomena/*genetics ; Evolution, Molecular ; Gene Transfer, Horizontal/genetics ; Genome, Bacterial/genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Symbiosis/*genetics ; }, abstract = {The Candidate Phyla Radiation (CPR) constitutes a large group of mostly uncultured bacterial lineages with small cell sizes and limited biosynthetic capabilities. They are thought to be symbionts of other organisms, but the nature of this symbiosis has been ascertained only for cultured Saccharibacteria, which are epibiotic parasites of other bacteria. Here, we study the biology and the genome of Vampirococcus lugosii, which becomes the first described species of Vampirococcus, a genus of epibiotic bacteria morphologically identified decades ago. Vampirococcus belongs to the CPR phylum Absconditabacteria. It feeds on anoxygenic photosynthetic gammaproteobacteria, fully absorbing their cytoplasmic content. The cells divide epibiotically, forming multicellular stalks whose apical cells can reach new hosts. The genome is small (1.3 Mbp) and highly reduced in biosynthetic metabolism genes, but is enriched in genes possibly related to a fibrous cell surface likely involved in interactions with the host. Gene loss has been continuous during the evolution of Absconditabacteria, and generally most CPR bacteria, but this has been compensated by gene acquisition by horizontal gene transfer and de novo evolution. Our findings support parasitism as a widespread lifestyle of CPR bacteria, which probably contribute to the control of bacterial populations in diverse ecosystems.}, } @article {pmid33897656, year = {2021}, author = {Garg, R and Maldener, I}, title = {The Dual Role of the Glycolipid Envelope in Different Cell Types of the Multicellular Cyanobacterium Anabaena variabilis ATCC 29413.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {645028}, pmid = {33897656}, issn = {1664-302X}, abstract = {Anabaena variabilis is a filamentous cyanobacterium that is capable to differentiate specialized cells, the heterocysts and akinetes, to survive under different stress conditions. Under nitrogen limited condition, heterocysts provide the filament with nitrogen by fixing N2. Akinetes are spore-like dormant cells that allow survival during adverse environmental conditions. Both cell types are characterized by the presence of a thick multilayered envelope, including a glycolipid layer. While in the heterocyst this glycolipid layer is required for the maintenance of a microoxic environment and nitrogen fixation, its function in akinetes is completely unknown. Therefore, we constructed a mutant deficient in glycolipid synthesis and investigated the performance of heterocysts and akinetes in that mutant strain. We chose to delete the gene Ava_2595, which is homolog to the known hglB gene, encoding a putative polyketide synthase previously shown to be involved in heterocyst glycolipid synthesis in Anabaena sp. PCC 7120, a species which does not form akinetes. Under the respective conditions, the Ava_2595 null mutant strain formed aberrant heterocysts and akinete-like cells, in which the specific glycolipid layers were absent. This confirmed firstly that both cell types use a glycolipid of identical chemical composition in their special envelopes and, secondly, that HglB is essential for glycolipid synthesis in both types of differentiated cells. As a consequence, the mutant was not able to fix N2 and to grow under diazotrophic conditions. Furthermore, the akinetes lacking the glycolipids showed a severely reduced tolerance to stress conditions, but could germinate normally under standard conditions. This demonstrates the importance of the glycolipid layer for the ability of akinetes as spore-like dormant cells to withstand freezing, desiccation, oxidative stress and attack by lytic enzymes. Our study established the dual role of the glycolipid layer in fulfilling different functions in the evolutionary-related specialized cells of cyanobacteria. It also indicates the existence of a common pathway involving HglB for the synthesis of glycolipids in heterocysts and akinetes.}, } @article {pmid33892552, year = {2021}, author = {Huang, D and Wang, R}, title = {Exploring the mechanism of pancreatic cell fate decisions via cell-cell communication.}, journal = {Mathematical biosciences and engineering : MBE}, volume = {18}, number = {3}, pages = {2401-2424}, doi = {10.3934/mbe.2021122}, pmid = {33892552}, issn = {1551-0018}, mesh = {*Basic Helix-Loop-Helix Transcription Factors ; Cell Communication ; Cell Differentiation ; Pancreas ; *Receptors, Notch ; }, abstract = {The endocrine and exocrine cells in pancreas originate initially from a group of apparently identical endoderm cells in the early gut. The endocrine and exocrine tissues are composed of islet/acinar and duct cells respectively. To explore the mechanism of pancreas cell fate decisions, we first construct a minimal mathematical model related to pancreatic regulations. The regulatory mechanism of acinar-to-islet cell conversion is revealed by bifurcation analysis of the model. In addition, Notch signaling is critical in determining the fate of endocrine and exocrine in the developing pancreas and it is a typical mediator of lateral inhibition which instructs adjacent cells to make different fate decisions. Next, we construct a multicellular model of cell-cell communication mediated by Notch signaling with trans-activation and cis-inhibition. The roles of Notch signaling in regulating fate decisions of endocrine and exocrine cells during the differentiation of pancreatic cells are explored. The results indicate that high (or low) level of Notch signaling drive cells to select the fate of exocrine (or endocrine) progenitor cells. The networks and the models presented here might be good candidates for providing qualitative mechanisms of pancreatic cell fate decisions. These results can also provide some insight on choosing perturbation strategies for further experimental analysis.}, } @article {pmid33880702, year = {2021}, author = {Wang, Z and Sun, X and Zhang, X and Dong, B and Yu, H}, title = {Development of a miRNA Sensor by an Inducible CRISPR-Cas9 Construct in Ciona Embryogenesis.}, journal = {Molecular biotechnology}, volume = {63}, number = {7}, pages = {613-620}, pmid = {33880702}, issn = {1559-0305}, support = {2019YFE0190900//The National Key Research and Development Program of China/ ; 2018YFD0900705//The National Key Research and Development Program of China/ ; 201961017//The Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; CRISPR-Cas Systems ; Ciona/*embryology/genetics ; Gene Editing/*methods ; Gene Silencing ; MicroRNAs/*genetics ; RNA, Guide, Kinetoplastida/genetics ; }, abstract = {MicroRNAs (miRNAs) regulate multicellular processes and diverse signaling pathways in organisms. The detection of the spatiotemporal expression of miRNA in vivo is crucial for uncovering the function of miRNA. However, most of the current detecting techniques cannot reflect the dynamics of miRNA sensitively in vivo. Here, we constructed a miRNA-induced CRISPR-Cas9 platform (MICR) used in marine chordate Ciona. The key component of MICR is a pre-single guide RNA (sgRNA) flanked by miRNA-binding sites that can be released by RNA-induced silencing complex (RISC) cleavage to form functional sgRNA in the presence of complementary miRNA. By using the miRNA-inducible CRISPR-on system (MICR-ON), we successfully detected the dynamic expression of a miRNA csa-miR-4018a during development of Ciona embryo. The detected patterns were validated to be consistent with the results by in situ hybridization. It is worth noting that the expression of csa-miR-4018a was examined by MICR-ON to be present in additional tissues, where no obvious signaling was detected by in situ hybridization, suggesting that the MICR-ON might be a more sensitive approach to detect miRNA signal in living animal. Thus, MICR-ON was demonstrated to be a sensitive and highly efficient approach for monitoring the dynamics of expression of miRNA in vivo and will facilitate the exploration of miRNA functions in biological systems.}, } @article {pmid33875673, year = {2021}, author = {Thongsripong, P and Chandler, JA and Kittayapong, P and Wilcox, BA and Kapan, DD and Bennett, SN}, title = {Metagenomic shotgun sequencing reveals host species as an important driver of virome composition in mosquitoes.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {8448}, pmid = {33875673}, issn = {2045-2322}, support = {P01 AI106695/AI/NIAID NIH HHS/United States ; P20 RR018727/RR/NCRR NIH HHS/United States ; U54 AI065359/AI/NIAID NIH HHS/United States ; }, mesh = {Aedes/*virology ; Animals ; Culex/*virology ; *Genome, Viral ; High-Throughput Nucleotide Sequencing ; Host Specificity ; *Metagenome ; Mosquito Vectors/*virology ; Phylogeny ; RNA Viruses/*physiology ; RNA-Seq ; Thailand ; *Virome ; }, abstract = {High-throughput nucleic acid sequencing has greatly accelerated the discovery of viruses in the environment. Mosquitoes, because of their public health importance, are among those organisms whose viromes are being intensively characterized. Despite the deluge of sequence information, our understanding of the major drivers influencing the ecology of mosquito viromes remains limited. Using methods to increase the relative proportion of microbial RNA coupled with RNA-seq we characterize RNA viruses and other symbionts of three mosquito species collected along a rural to urban habitat gradient in Thailand. The full factorial study design allows us to explicitly investigate the relative importance of host species and habitat in structuring viral communities. We found that the pattern of virus presence was defined primarily by host species rather than by geographic locations or habitats. Our result suggests that insect-associated viruses display relatively narrow host ranges but are capable of spreading through a mosquito population at the geographical scale of our study. We also detected various single-celled and multicellular microorganisms such as bacteria, alveolates, fungi, and nematodes. Our study emphasizes the importance of including ecological information in viromic studies in order to gain further insights into viral ecology in systems where host specificity is driving both viral ecology and evolution.}, } @article {pmid33865960, year = {2021}, author = {Hage, H and Rosso, MN and Tarrago, L}, title = {Distribution of methionine sulfoxide reductases in fungi and conservation of the free-methionine-R-sulfoxide reductase in multicellular eukaryotes.}, journal = {Free radical biology & medicine}, volume = {169}, number = {}, pages = {187-215}, doi = {10.1016/j.freeradbiomed.2021.04.013}, pmid = {33865960}, issn = {1873-4596}, mesh = {*Eukaryota/metabolism ; Fungi/genetics ; Methionine/metabolism ; *Methionine Sulfoxide Reductases/genetics/metabolism ; Oxidation-Reduction ; Phylogeny ; }, abstract = {Methionine, either as a free amino acid or included in proteins, can be oxidized into methionine sulfoxide (MetO), which exists as R and S diastereomers. Almost all characterized organisms possess thiol-oxidoreductases named methionine sulfoxide reductase (Msr) enzymes to reduce MetO back to Met. MsrA and MsrB reduce the S and R diastereomers of MetO, respectively, with strict stereospecificity and are found in almost all organisms. Another type of thiol-oxidoreductase, the free-methionine-R-sulfoxide reductase (fRMsr), identified so far in prokaryotes and a few unicellular eukaryotes, reduces the R MetO diastereomer of the free amino acid. Moreover, some bacteria possess molybdenum-containing enzymes that reduce MetO, either in the free or protein-bound forms. All these Msrs play important roles in the protection of organisms against oxidative stress. Fungi are heterotrophic eukaryotes that colonize all niches on Earth and play fundamental functions, in organic matter recycling, as symbionts, or as pathogens of numerous organisms. However, our knowledge on fungal Msrs is still limited. Here, we performed a survey of msr genes in almost 700 genomes across the fungal kingdom. We show that most fungi possess one gene coding for each type of methionine sulfoxide reductase: MsrA, MsrB, and fRMsr. However, several fungi living in anaerobic environments or as obligate intracellular parasites were devoid of msr genes. Sequence inspection and phylogenetic analyses allowed us to identify non-canonical sequences with potentially novel enzymatic properties. Finaly, we identified several ocurences of msr horizontal gene transfer from bacteria to fungi.}, } @article {pmid33865238, year = {2021}, author = {Xu, X and Smaczniak, C and Muino, JM and Kaufmann, K}, title = {Cell identity specification in plants: lessons from flower development.}, journal = {Journal of experimental botany}, volume = {72}, number = {12}, pages = {4202-4217}, pmid = {33865238}, issn = {1460-2431}, mesh = {Cell Differentiation ; Flowers/metabolism ; Gene Expression Regulation, Developmental ; *Gene Expression Regulation, Plant ; *Plants/genetics/metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {Multicellular organisms display a fascinating complexity of cellular identities and patterns of diversification. The concept of 'cell type' aims to describe and categorize this complexity. In this review, we discuss the traditional concept of cell types and highlight the impact of single-cell technologies and spatial omics on the understanding of cellular differentiation in plants. We summarize and compare position-based and lineage-based mechanisms of cell identity specification using flower development as a model system. More than understanding ontogenetic origins of differentiated cells, an important question in plant science is to understand their position- and developmental stage-specific heterogeneity. Combinatorial action and crosstalk of external and internal signals is the key to cellular heterogeneity, often converging on transcription factors that orchestrate gene expression programs.}, } @article {pmid33861755, year = {2021}, author = {Menichelli, C and Guitard, V and Martins, RM and Lèbre, S and Lopez-Rubio, JJ and Lecellier, CH and Bréhélin, L}, title = {Identification of long regulatory elements in the genome of Plasmodium falciparum and other eukaryotes.}, journal = {PLoS computational biology}, volume = {17}, number = {4}, pages = {e1008909}, pmid = {33861755}, issn = {1553-7358}, mesh = {Eukaryota/genetics ; Gene Expression Regulation ; Gene Ontology ; Genes, Reporter ; *Genome, Protozoan ; Histones/metabolism ; Plasmodium falciparum/*genetics ; RNA Processing, Post-Transcriptional ; RNA, Antisense/genetics ; RNA, Messenger/genetics ; *Regulatory Sequences, Nucleic Acid ; Transcription, Genetic ; }, abstract = {Long regulatory elements (LREs), such as CpG islands, polydA:dT tracts or AU-rich elements, are thought to play key roles in gene regulation but, as opposed to conventional binding sites of transcription factors, few methods have been proposed to formally and automatically characterize them. We present here a computational approach named DExTER (Domain Exploration To Explain gene Regulation) dedicated to the identification of candidate LREs (cLREs) and apply it to the analysis of the genomes of P. falciparum and other eukaryotes. Our analyses show that all tested genomes contain several cLREs that are somewhat conserved along evolution, and that gene expression can be predicted with surprising accuracy on the basis of these long regions only. Regulation by cLREs exhibits very different behaviours depending on species and conditions. In P. falciparum and other Apicomplexan organisms as well as in Dictyostelium discoideum, the process appears highly dynamic, with different cLREs involved at different phases of the life cycle. For multicellular organisms, the same cLREs are involved in all tissues, but a dynamic behavior is observed along embryonic development stages. In P. falciparum, whose genome is known to be strongly depleted of transcription factors, cLREs are predictive of expression with an accuracy above 70%, and our analyses show that they are associated with both transcriptional and post-transcriptional regulation signals. Moreover, we assessed the biological relevance of one LRE discovered by DExTER in P. falciparum using an in vivo reporter assay. The source code (python) of DExTER is available at https://gite.lirmm.fr/menichelli/DExTER.}, } @article {pmid33852871, year = {2021}, author = {Strother, PK and Brasier, MD and Wacey, D and Timpe, L and Saunders, M and Wellman, CH}, title = {A possible billion-year-old holozoan with differentiated multicellularity.}, journal = {Current biology : CB}, volume = {31}, number = {12}, pages = {2658-2665.e2}, doi = {10.1016/j.cub.2021.03.051}, pmid = {33852871}, issn = {1879-0445}, mesh = {Cell Differentiation ; *Fossils ; Phylogeny ; }, abstract = {Sediments of the Torridonian sequence of the Northwest Scottish Highlands contain a wide array of microfossils, documenting life in a non-marine setting a billion years ago (1 Ga).[1-4] Phosphate nodules from the Diabaig Formation at Loch Torridon preserve microorganisms with cellular-level fidelity,[5][,][6] allowing for partial reconstruction of the developmental stages of a new organism, Bicellum brasieri gen. et sp. nov. The mature form of Bicellum consists of a solid, spherical ball of tightly packed cells (a stereoblast) of isodiametric cells enclosed in a monolayer of elongated, sausage-shaped cells. However, two populations of naked stereoblasts show mixed cell shapes, which we infer to indicate incipient development of elongated cells that were migrating to the periphery of the cell mass. These simple morphogenetic movements could be explained by differential cell-cell adhesion.[7][,][8] In fact, the basic morphology of Bicellum is topologically similar to that of experimentally produced cell masses that were shown to spontaneously segregate into two distinct domains based on differential cadherin-based cell adhesion.[9] The lack of rigid cell walls in the stereoblast renders an algal affinity for Bicellum unlikely: its overall morphology is more consistent with a holozoan origin. Unicellular holozoans are known today to form multicellular stages within complex life cycles,[10-13] so the occurrence of such simple levels of transient multicellularity seen here is consistent with a holozoan affinity. Regardless of precise phylogenetic placement, these fossils demonstrate simple cell differentiation and morphogenic processes that are similar to those seen in some metazoans today.}, } @article {pmid33850152, year = {2021}, author = {Brosnan, CA and Palmer, AJ and Zuryn, S}, title = {Cell-type-specific profiling of loaded miRNAs from Caenorhabditis elegans reveals spatial and temporal flexibility in Argonaute loading.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2194}, pmid = {33850152}, issn = {2041-1723}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Argonaute Proteins/*genetics/*metabolism ; Caenorhabditis elegans/*genetics ; Caenorhabditis elegans Proteins/genetics/metabolism ; Gene Expression Regulation ; MicroRNAs/*genetics/*metabolism ; Nervous System ; Protein Isoforms ; }, abstract = {Multicellularity has coincided with the evolution of microRNAs (miRNAs), small regulatory RNAs that are integrated into cellular differentiation and homeostatic gene-regulatory networks. However, the regulatory mechanisms underpinning miRNA activity have remained largely obscured because of the precise, and thus difficult to access, cellular contexts under which they operate. To resolve these, we have generated a genome-wide map of active miRNAs in Caenorhabditis elegans by revealing cell-type-specific patterns of miRNAs loaded into Argonaute (AGO) silencing complexes. Epitope-labelled AGO proteins were selectively expressed and immunoprecipitated from three distinct tissue types and associated miRNAs sequenced. In addition to providing information on biological function, we define adaptable miRNA:AGO interactions with single-cell-type and AGO-specific resolution. We demonstrate spatial and temporal dynamicism, flexibility of miRNA loading, and suggest miRNA regulatory mechanisms via AGO selectivity in different tissues and during ageing. Additionally, we resolve widespread changes in AGO-regulated gene expression by analysing translatomes specifically in neurons.}, } @article {pmid33846299, year = {2021}, author = {Shemesh, N and Jubran, J and Dror, S and Simonovsky, E and Basha, O and Argov, C and Hekselman, I and Abu-Qarn, M and Vinogradov, E and Mauer, O and Tiago, T and Carra, S and Ben-Zvi, A and Yeger-Lotem, E}, title = {The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2180}, pmid = {33846299}, issn = {2041-1723}, mesh = {Aging/metabolism ; Animals ; Caenorhabditis elegans/metabolism ; Cell Line ; Conserved Sequence ; Evolution, Molecular ; Gene Expression Regulation ; Humans ; Mice ; Molecular Chaperones/genetics/*metabolism ; Open Reading Frames/genetics ; *Organ Specificity/genetics ; }, abstract = {The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, the organization of the chaperone system across physiological human tissues has received little attention. Through computational analyses of large-scale tissue transcriptomes, we unveil that the chaperone system is composed of core elements that are uniformly expressed across tissues, and variable elements that are differentially expressed to fit with tissue-specific requirements. We demonstrate via a proteomic analysis that the muscle-specific signature is functional and conserved. Core chaperones are significantly more abundant across tissues and more important for cell survival than variable chaperones. Together with variable chaperones, they form tissue-specific functional networks. Analysis of human organ development and aging brain transcriptomes reveals that these functional networks are established in development and decline with age. In this work, we expand the known functional organization of de novo versus stress-inducible eukaryotic chaperones into a layered core-variable architecture in multi-cellular organisms.}, } @article {pmid33839924, year = {2021}, author = {Genau, AC and Li, Z and Renzaglia, KS and Fernandez Pozo, N and Nogué, F and Haas, FB and Wilhelmsson, PKI and Ullrich, KK and Schreiber, M and Meyberg, R and Grosche, C and Rensing, SA}, title = {HAG1 and SWI3A/B control of male germ line development in P. patens suggests conservation of epigenetic reproductive control across land plants.}, journal = {Plant reproduction}, volume = {34}, number = {2}, pages = {149-173}, pmid = {33839924}, issn = {2194-7961}, support = {5R25GM107760-07/NH/NIH HHS/United States ; R25 GM107760/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; *Embryophyta ; Epigenesis, Genetic ; *Germ Cells, Plant ; Reproduction/genetics ; }, abstract = {Bryophytes as models to study the male germ line: loss-of-function mutants of epigenetic regulators HAG1 and SWI3a/b demonstrate conserved function in sexual reproduction. With the water-to-land transition, land plants evolved a peculiar haplodiplontic life cycle in which both the haploid gametophyte and the diploid sporophyte are multicellular. The switch between these phases was coined alternation of generations. Several key regulators that control the bauplan of either generation are already known. Analyses of such regulators in flowering plants are difficult due to the highly reduced gametophytic generation, and the fact that loss of function of such genes often is embryo lethal in homozygous plants. Here we set out to determine gene function and conservation via studies in bryophytes. Bryophytes are sister to vascular plants and hence allow evolutionary inferences. Moreover, embryo lethal mutants can be grown and vegetatively propagated due to the dominance of the bryophyte gametophytic generation. We determined candidates by selecting single copy orthologs that are involved in transcriptional control, and of which flowering plant mutants show defects during sexual reproduction, with a focus on the under-studied male germ line. We selected two orthologs, SWI3a/b and HAG1, and analyzed loss-of-function mutants in the moss P. patens. In both mutants, due to lack of fertile spermatozoids, fertilization and hence the switch to the diploid generation do not occur. Pphag1 additionally shows arrested male and impaired female gametangia development. We analyzed HAG1 in the dioecious liverwort M. polymorpha and found that in Mphag1 the development of gametangiophores is impaired. Taken together, we find that involvement of both regulators in sexual reproduction is conserved since the earliest divergence of land plants.}, } @article {pmid33837641, year = {2021}, author = {Abe-Fukasawa, N and Watanabe, R and Gen, Y and Nishino, T and Itasaki, N}, title = {A liquid culture cancer spheroid model reveals low PI3K/Akt pathway activity and low adhesiveness to the extracellular matrix.}, journal = {The FEBS journal}, volume = {288}, number = {19}, pages = {5650-5667}, doi = {10.1111/febs.15867}, pmid = {33837641}, issn = {1742-4658}, mesh = {Animals ; Cell Adhesion/*genetics ; *Cell Culture Techniques ; Cell Line, Tumor ; Cell Polarity/genetics ; Extracellular Matrix/genetics ; Humans ; Mice ; Neoplasm Metastasis ; Neoplasms/*genetics/pathology ; Oncogene Protein v-akt/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Signal Transduction/genetics ; Spheroids, Cellular/metabolism/*pathology ; Transplantation, Heterologous ; }, abstract = {Three-dimensional (3D) cultures of cancer cells in liquid without extracellular matrix (ECM) offer in vitro models for metastasising conditions such as those in vessels and effusion. However, liquid culturing is often hindered by cell adhesiveness, which causes large cell clumps. We previously described a liquid culture material, LA717, which prevents nonclonal cell adhesion and subsequent clumping, thus allowing clonal growth of spheroids in an anchorage-independent manner. Here, we examined such liquid culture cancer spheroids for the acquisition of apical-basal polarity, sensitivity to an Akt inhibitor (anticancer drug MK-2206) and interaction with ECM. The spheroids present apical plasma membrane on the surface, which originated from the failure of polarisation at the single-cell stage and subsequent defects in phosphorylated ezrin accumulation at the cell boundary during the first cleavage, failing internal lumen formation. At the multicellular stage, liquid culture spheroids presented bleb-like protrusion on the surface, which was enhanced by the activation of the PI3K/Akt pathway and reduced by PI3K/Akt inhibitors. Liquid culture spheroids exhibited slow proliferation speed and low endogenous pAkt levels compared with gel-cultured spheroids and 2D-cultured cells, explaining the susceptibility to the Akt-inhibiting anticancer drug. Subcutaneous xenografting and in vitro analysis demonstrated low viability and adhesive property of liquid culture spheroids to ECM, while migratory and invasive capacities were comparable with gel-cultured spheroids. These features agree with the low efficacy of circulating tumour spheroids in the settling step of metastasis. This study demonstrates the feature of anchorage-independent spheroids and validates liquid cultures as a useful method in cancer spheroid research.}, } @article {pmid33834782, year = {2021}, author = {Kwon, HY and Kumar Das, R and Jung, GT and Lee, HG and Lee, SH and Berry, SN and Tan, JKS and Park, S and Yang, JS and Park, S and Baek, K and Park, KM and Lee, JW and Choi, YK and Kim, KH and Kim, S and Kim, KP and Kang, NY and Kim, K and Chang, YT}, title = {Lipid-Oriented Live-Cell Distinction of B and T Lymphocytes.}, journal = {Journal of the American Chemical Society}, volume = {143}, number = {15}, pages = {5836-5844}, doi = {10.1021/jacs.1c00944}, pmid = {33834782}, issn = {1520-5126}, mesh = {Animals ; B-Lymphocytes/chemistry/*cytology/immunology ; Bone Marrow Cells/cytology/metabolism ; Cell Differentiation ; Cell Membrane/chemistry/*metabolism ; Flow Cytometry ; Fluorescent Dyes/*chemistry ; Lipidomics ; Mice ; T-Lymphocytes/chemistry/*cytology/immunology ; }, abstract = {The identification of each cell type is essential for understanding multicellular communities. Antibodies set as biomarkers have been the main toolbox for cell-type recognition, and chemical probes are emerging surrogates. Herein we report the first small-molecule probe, CDgB, to discriminate B lymphocytes from T lymphocytes, which was previously impossible without the help of antibodies. Through the study of the origin of cell specificity, we discovered an unexpected novel mechanism of membrane-oriented live-cell distinction. B cells maintain higher flexibility in their cell membrane than T cells and accumulate the lipid-like probe CDgB more preferably. Because B and T cells share common ancestors, we tracked the cell membrane changes of the progenitor cells and disclosed the dynamic reorganization of the membrane properties over the lymphocyte differentiation progress. This study casts an orthogonal strategy for the small-molecule cell identifier and enriches the toolbox for live-cell distinction from complex cell communities.}, } @article {pmid33816460, year = {2021}, author = {Vassalli, QA and Colantuono, C and Nittoli, V and Ferraioli, A and Fasano, G and Berruto, F and Chiusano, ML and Kelsh, RN and Sordino, P and Locascio, A}, title = {Onecut Regulates Core Components of the Molecular Machinery for Neurotransmission in Photoreceptor Differentiation.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {602450}, pmid = {33816460}, issn = {2296-634X}, abstract = {Photoreceptor cells (PRC) are neurons highly specialized for sensing light stimuli and have considerably diversified during evolution. The genetic mechanisms that underlie photoreceptor differentiation and accompanied the progressive increase in complexity and diversification of this sensory cell type are a matter of great interest in the field. A role of the homeodomain transcription factor Onecut (Oc) in photoreceptor cell formation is proposed throughout multicellular organisms. However, knowledge of the identity of the Oc downstream-acting factors that mediate specific tasks in the differentiation of the PRC remains limited. Here, we used transgenic perturbation of the Ciona robusta Oc protein to show its requirement for ciliary PRC differentiation. Then, transcriptome profiling between the trans-activation and trans-repression Oc phenotypes identified differentially expressed genes that are enriched in exocytosis, calcium homeostasis, and neurotransmission. Finally, comparison of RNA-Seq datasets in Ciona and mouse identifies a set of Oc downstream genes conserved between tunicates and vertebrates. The transcription factor Oc emerges as a key regulator of neurotransmission in retinal cell types.}, } @article {pmid33803228, year = {2021}, author = {Marter, P and Huang, S and Brinkmann, H and Pradella, S and Jarek, M and Rohde, M and Bunk, B and Petersen, J}, title = {Filling the Gaps in the Cyanobacterial Tree of Life-Metagenome Analysis of Stigonema ocellatum DSM 106950, Chlorogloea purpurea SAG 13.99 and Gomphosphaeria aponina DSM 107014.}, journal = {Genes}, volume = {12}, number = {3}, pages = {}, pmid = {33803228}, issn = {2073-4425}, mesh = {Cyanobacteria/*genetics ; Genome, Bacterial/genetics ; Metagenome/*genetics ; Metagenomics/methods ; Microbiota/genetics ; Phylogeny ; }, abstract = {Cyanobacteria represent one of the most important and diverse lineages of prokaryotes with an unparalleled morphological diversity ranging from unicellular cocci and characteristic colony-formers to multicellular filamentous strains with different cell types. Sequencing of more than 1200 available reference genomes was mainly driven by their ecological relevance (Prochlorococcus, Synechococcus), toxicity (Microcystis) and the availability of axenic strains. In the current study three slowly growing non-axenic cyanobacteria with a distant phylogenetic positioning were selected for metagenome sequencing in order to (i) investigate their genomes and to (ii) uncover the diversity of associated heterotrophs. High-throughput Illumina sequencing, metagenomic assembly and binning allowed us to establish nearly complete high-quality draft genomes of all three cyanobacteria and to determine their phylogenetic position. The cyanosphere of the limnic isolates comprises up to 40 heterotrophic bacteria that likely coexisted for several decades, and it is dominated by Alphaproteobacteria and Bacteriodetes. The diagnostic marker protein RpoB ensured in combination with our novel taxonomic assessment via BLASTN-dependent text-mining a reliable classification of the metagenome assembled genomes (MAGs). The detection of one new family and more than a dozen genera of uncultivated heterotrophic bacteria illustrates that non-axenic cyanobacteria are treasure troves of hidden microbial diversity.}, } @article {pmid33802617, year = {2021}, author = {Baluška, F and Miller, WB and Reber, AS}, title = {Biomolecular Basis of Cellular Consciousness via Subcellular Nanobrains.}, journal = {International journal of molecular sciences}, volume = {22}, number = {5}, pages = {}, pmid = {33802617}, issn = {1422-0067}, mesh = {Animals ; Biological Evolution ; Cell Biology ; Cell Membrane/*physiology ; Consciousness/*physiology ; }, abstract = {Cells emerged at the very beginning of life on Earth and, in fact, are coterminous with life. They are enclosed within an excitable plasma membrane, which defines the outside and inside domains via their specific biophysical properties. Unicellular organisms, such as diverse protists and algae, still live a cellular life. However, fungi, plants, and animals evolved a multicellular existence. Recently, we have developed the cellular basis of consciousness (CBC) model, which proposes that all biological awareness, sentience and consciousness are grounded in general cell biology. Here we discuss the biomolecular structures and processes that allow for and maintain this cellular consciousness from an evolutionary perspective.}, } @article {pmid33801615, year = {2021}, author = {Kin, K and Schaap, P}, title = {Evolution of Multicellular Complexity in The Dictyostelid Social Amoebas.}, journal = {Genes}, volume = {12}, number = {4}, pages = {}, pmid = {33801615}, issn = {2073-4425}, support = {742288/ERC_/European Research Council/International ; 100293/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Amoeba/*physiology ; Biological Evolution ; Cold Temperature ; Dictyostelium/*physiology ; Evolution, Molecular ; Life Cycle Stages ; Phylogeny ; Signal Transduction ; *Stress, Physiological ; }, abstract = {Multicellularity evolved repeatedly in the history of life, but how it unfolded varies greatly between different lineages. Dictyostelid social amoebas offer a good system to study the evolution of multicellular complexity, with a well-resolved phylogeny and molecular genetic tools being available. We compare the life cycles of the Dictyostelids with closely related amoebozoans to show that complex life cycles were already present in the unicellular common ancestor of Dictyostelids. We propose frost resistance as an early driver of multicellular evolution in Dictyostelids and show that the cell signalling pathways for differentiating spore and stalk cells evolved from that for encystation. The stalk cell differentiation program was further modified, possibly through gene duplication, to evolve a new cell type, cup cells, in Group 4 Dictyostelids. Studies in various multicellular organisms, including Dictyostelids, volvocine algae, and metazoans, suggest as a common principle in the evolution of multicellular complexity that unicellular regulatory programs for adapting to environmental change serve as "proto-cell types" for subsequent evolution of multicellular organisms. Later, new cell types could further evolve by duplicating and diversifying the "proto-cell type" gene regulatory networks.}, } @article {pmid33800339, year = {2021}, author = {Patthy, L}, title = {Exon Shuffling Played a Decisive Role in the Evolution of the Genetic Toolkit for the Multicellular Body Plan of Metazoa.}, journal = {Genes}, volume = {12}, number = {3}, pages = {}, pmid = {33800339}, issn = {2073-4425}, mesh = {Animals ; *Cell Differentiation ; *Evolution, Molecular ; *Exons ; *Models, Genetic ; Transcription Factors/*genetics ; }, abstract = {Division of labor and establishment of the spatial pattern of different cell types of multicellular organisms require cell type-specific transcription factor modules that control cellular phenotypes and proteins that mediate the interactions of cells with other cells. Recent studies indicate that, although constituent protein domains of numerous components of the genetic toolkit of the multicellular body plan of Metazoa were present in the unicellular ancestor of animals, the repertoire of multidomain proteins that are indispensable for the arrangement of distinct body parts in a reproducible manner evolved only in Metazoa. We have shown that the majority of the multidomain proteins involved in cell-cell and cell-matrix interactions of Metazoa have been assembled by exon shuffling, but there is no evidence for a similar role of exon shuffling in the evolution of proteins of metazoan transcription factor modules. A possible explanation for this difference in the intracellular and intercellular toolkits is that evolution of the transcription factor modules preceded the burst of exon shuffling that led to the creation of the proteins controlling spatial patterning in Metazoa. This explanation is in harmony with the temporal-to-spatial transition hypothesis of multicellularity that proposes that cell differentiation may have predated spatial segregation of cell types in animal ancestors.}, } @article {pmid33795155, year = {2021}, author = {Vos, M}, title = {Myxococcus xanthus.}, journal = {Trends in microbiology}, volume = {29}, number = {6}, pages = {562-563}, doi = {10.1016/j.tim.2021.03.006}, pmid = {33795155}, issn = {1878-4380}, mesh = {Bacterial Proteins/genetics/metabolism ; Genome, Bacterial ; Metabolome ; Movement ; Myxococcus xanthus/*genetics/*metabolism ; Secondary Metabolism ; Soil Microbiology ; }, } @article {pmid33779495, year = {2022}, author = {Porfírio-Sousa, AL and Tice, AK and Brown, MW and J G Lahr, D}, title = {Phylogenetic reconstruction and evolution of the Rab GTPase gene family in Amoebozoa.}, journal = {Small GTPases}, volume = {13}, number = {1}, pages = {100-113}, pmid = {33779495}, issn = {2154-1256}, mesh = {Phylogeny ; *rab GTP-Binding Proteins/genetics/metabolism ; Evolution, Molecular ; *Amoebozoa/genetics/metabolism ; Eukaryota/metabolism ; }, abstract = {Rab GTPase is a paralog-rich gene family that controls the maintenance of the eukaryotic cell compartmentalization system. Diverse eukaryotes have varying numbers of Rab paralogs. Currently, little is known about the evolutionary pattern of Rab GTPase in most major eukaryotic 'supergroups'. Here, we present a comprehensive phylogenetic reconstruction of the Rab GTPase gene family in the eukaryotic 'supergroup' Amoebozoa, a diverse lineage represented by unicellular and multicellular organisms. We demonstrate that Amoebozoa conserved 20 of the 23 ancestral Rab GTPases predicted to be present in the last eukaryotic common ancestor and massively expanded several 'novel' in-paralogs. Due to these 'novel' in-paralogs, the Rab family composition dramatically varies between the members of Amoebozoa; as a consequence, 'supergroup'-based studies may significantly change our current understanding of the evolution and diversity of this gene family. The high diversity of the Rab GTPase gene family in Amoebozoa makes this 'supergroup' a key lineage to study and advance our knowledge of the evolution of Rab in Eukaryotes.}, } @article {pmid33767367, year = {2021}, author = {Wang, S and Liang, H and Xu, Y and Li, L and Wang, H and Sahu, DN and Petersen, M and Melkonian, M and Sahu, SK and Liu, H}, title = {Genome-wide analyses across Viridiplantae reveal the origin and diversification of small RNA pathway-related genes.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {412}, pmid = {33767367}, issn = {2399-3642}, mesh = {*Evolution, Molecular ; Genes, Plant ; *Genome, Plant ; Phylogeny ; RNA, Small Untranslated/*genetics ; Viridiplantae/*genetics ; }, abstract = {Small RNAs play a major role in the post-transcriptional regulation of gene expression in eukaryotes. Despite the evolutionary importance of streptophyte algae, knowledge on small RNAs in this group of green algae is almost non-existent. We used genome and transcriptome data of 34 algal and plant species, and performed genome-wide analyses of small RNA (miRNA & siRNA) biosynthetic and degradation pathways. The results suggest that Viridiplantae started to evolve plant-like miRNA biogenesis and degradation after the divergence of the Mesostigmatophyceae in the streptophyte algae. We identified two major evolutionary transitions in small RNA metabolism in streptophyte algae; during the first transition, the origin of DCL-New, DCL1, AGO1/5/10 and AGO4/6/9 in the last common ancestor of Klebsormidiophyceae and all other streptophytes could be linked to abiotic stress responses and evolution of multicellularity in streptophytes. During the second transition, the evolution of DCL 2,3,4, and AGO 2,3,7 as well as DRB1 in the last common ancestor of Zygnematophyceae and embryophytes, suggests their possible contribution to pathogen defense and antibacterial immunity. Overall, the origin and diversification of DICER and AGO along with several other small RNA pathway-related genes among streptophyte algae suggested progressive adaptations of streptophyte algae during evolution to a subaerial environment.}, } @article {pmid33763054, year = {2020}, author = {Roudaire, T and Héloir, MC and Wendehenne, D and Zadoroznyj, A and Dubrez, L and Poinssot, B}, title = {Cross Kingdom Immunity: The Role of Immune Receptors and Downstream Signaling in Animal and Plant Cell Death.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {612452}, pmid = {33763054}, issn = {1664-3224}, mesh = {Animals ; Cell Death/*immunology ; Humans ; Immunity, Innate/immunology ; Inflammasomes/immunology ; Plant Cells/*immunology ; Plant Immunity/*immunology ; Plants/*immunology ; Receptors, Immunologic/*immunology ; Receptors, Pattern Recognition/immunology ; Signal Transduction/*immunology ; }, abstract = {Both plants and animals are endowed with sophisticated innate immune systems to combat microbial attack. In these multicellular eukaryotes, innate immunity implies the presence of cell surface receptors and intracellular receptors able to detect danger signal referred as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). Membrane-associated pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), C-type lectin receptors (CLRs), receptor-like kinases (RLKs), and receptor-like proteins (RLPs) are employed by these organisms for sensing different invasion patterns before triggering antimicrobial defenses that can be associated with a form of regulated cell death. Intracellularly, animals nucleotide-binding and oligomerization domain (NOD)-like receptors or plants nucleotide-binding domain (NBD)-containing leucine rich repeats (NLRs) immune receptors likely detect effectors injected into the host cell by the pathogen to hijack the immune signaling cascade. Interestingly, during the co-evolution between the hosts and their invaders, key cross-kingdom cell death-signaling macromolecular NLR-complexes have been selected, such as the inflammasome in mammals and the recently discovered resistosome in plants. In both cases, a regulated cell death located at the site of infection constitutes a very effective mean for blocking the pathogen spread and protecting the whole organism from invasion. This review aims to describe the immune mechanisms in animals and plants, mainly focusing on cell death signaling pathways, in order to highlight recent advances that could be used on one side or the other to identify the missing signaling elements between the perception of the invasion pattern by immune receptors, the induction of defenses or the transmission of danger signals to other cells. Although knowledge of plant immunity is less advanced, these organisms have certain advantages allowing easier identification of signaling events, regulators and executors of cell death, which could then be exploited directly for crop protection purposes or by analogy for medical research.}, } @article {pmid33760661, year = {2021}, author = {Barnett, AM and Mullaney, JA and Hendriks, C and Le Borgne, L and McNabb, WC and Roy, NC}, title = {Porcine colonoids and enteroids keep the memory of their origin during regeneration.}, journal = {American journal of physiology. Cell physiology}, volume = {320}, number = {5}, pages = {C794-C805}, doi = {10.1152/ajpcell.00420.2020}, pmid = {33760661}, issn = {1522-1563}, mesh = {Animals ; Biomarkers/metabolism ; *Cell Differentiation ; *Cell Lineage ; Cell Proliferation ; Colon/cytology/metabolism/*physiology ; Gene Expression Regulation ; Ileum/cytology/metabolism/*physiology ; Intestinal Mucosa/cytology/metabolism/*physiology ; Male ; Organoids/cytology/metabolism/*physiology ; Phenotype ; Signal Transduction ; Sus scrofa ; Time Factors ; Tissue Culture Techniques ; Transcriptome ; }, abstract = {The development of alternative in vitro culture methods has increased in the last decade as three-dimensional organoids of various tissues, including those of the small and large intestines. Due to their multicellular composition, organoids offer advantages over traditionally used immortalized or primary cell lines. However, organoids must be accurate models of their tissues of origin. This study compared gene expression profiles with respect to markers of specific cell types (stem cells, enterocytes, goblet, and enteroendocrine cells) and barrier maturation (tight junctions) of colonoid and enteroid cultures with their tissues of origin and colonoids with enteroids. Colonoids derived from three healthy pigs formed multilobed structures with a monolayer of cells similar to the crypt structures in colonic tissue. Colonoid and enteroid gene expression signatures were more similar to those found for the tissues of their origin than to each other. However, relative to their derived tissues, organoids had increased gene expression levels of stem cell markers Sox9 and Lgr5 encoding sex-determining region Y-box 9 and leucine-rich repeat-containing G protein-coupled rector 5, respectively. In contrast, expression levels of Occl and Zo1 encoding occludin and zonula occludens 1, respectively, were decreased. Expression levels of the cell lineage markers Atoh1, Cga, and Muc2 encoding atonal homolog 1, chromogranin A, and mucin 2, respectively, were decreased in colonoids, whereas Sglt1 and Apn encoding sodium-glucose transporter 1 and aminopeptidase A, respectively, were decreased in enteroids. These results indicate colonoid and enteroid cultures were predominantly comprised of undifferentiated cell types with decreased barrier maturation relative to their tissues of origin.}, } @article {pmid33748102, year = {2021}, author = {Dhakshinamoorthy, R and Singh, SP}, title = {Evolution of Reproductive Division of Labor - Lessons Learned From the Social Amoeba Dictyostelium discoideum During Its Multicellular Development.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {599525}, pmid = {33748102}, issn = {2296-634X}, abstract = {The origin of multicellular life from unicellular beings is an epochal step in the evolution of eukaryotes. There are several factors influencing cell fate choices during differentiation and morphogenesis of an organism. Genetic make-up of two cells that unite and fertilize is the key factor to signal the formation of various cell-types in due course of development. Although ploidy of the cell-types determines the genetics of an individual, the role of ploidy in cell fate decisions remains unclear. Dictyostelium serves as a versatile model to study the emergence of multicellular life from unicellular life forms. In this work, we investigate the role played by ploidy status of a cell on cell fate commitments during Dictyostelium development. To answer this question, we created Dictyostelium cells of different ploidy: haploid parents and derived isogenic diploids, allowing them to undergo development. The diploid strains used in this study were generated using parasexual genetics. The ploidy status of the haploids and diploids were confirmed by microscopy, flow cytometry, and karyotyping. Prior to reconstitution, we labeled the cells by two methods. First, intragenic expression of red fluorescent protein (RFP) and second, staining the amoebae with a vital, fluorescent dye carboxyfluorescein succinimidyl ester (CFSE). RFP labeled haploid cells allowed us to track the haploids in the chimeric aggregates, slugs, and fruiting bodies. The CFSE labeling method allowed us to track both the haploids and the diploids in the chimeric developmental structures. Our findings illustrate that the haploids demonstrate sturdy cell fate commitment starting from the aggregation stage. The haploids remain crowded at the aggregation centers of the haploid-diploid chimeric aggregates. At the slug stage haploids are predominantly occupying the slug posterior, and are visible in the spore population in the fruiting bodies. Our findings show that cell fate decisions during D. discoideum development are highly influenced by the ploidy status of a cell, adding a new aspect to already known factors Here, we report that ploidy status of a cell could also play a crucial role in regulating the cell fate commitments.}, } @article {pmid33745906, year = {2021}, author = {Johnson, JD and White, NL and Kangabire, A and Abrams, DM}, title = {A dynamical model for the origin of anisogamy.}, journal = {Journal of theoretical biology}, volume = {521}, number = {}, pages = {110669}, doi = {10.1016/j.jtbi.2021.110669}, pmid = {33745906}, issn = {1095-8541}, mesh = {*Biological Evolution ; Computer Simulation ; Female ; Germ Cells ; Humans ; Male ; *Models, Biological ; Reproduction ; }, abstract = {The vast majority of multi-cellular organisms are anisogamous, meaning that male and female sex cells differ in size. It remains an open question how this asymmetric state evolved, presumably from the symmetric isogamous state where all gametes are roughly the same size (drawn from the same distribution). Here, we use tools from the study of nonlinear dynamical systems to develop a simple mathematical model for this phenomenon. Unlike some prior work, we do not assume the existence of mating types. We also model frequency dependent selection via "mean-field coupling," whereby the likelihood that a gamete survives is an increasing function of its size relative to the population's mean gamete size. Using theoretical analysis and numerical simulation, we demonstrate that this mean-referenced competition will almost inevitably result in a stable anisogamous equilibrium, and thus isogamy may naturally lead to anisogamy.}, } @article {pmid33741994, year = {2021}, author = {Redmond, AK and McLysaght, A}, title = {Evidence for sponges as sister to all other animals from partitioned phylogenomics with mixture models and recoding.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {1783}, pmid = {33741994}, issn = {2041-1723}, mesh = {Animals ; Biological Evolution ; Ctenophora/classification/*genetics ; Genome/*genetics ; Genomics/*methods ; Models, Genetic ; *Phylogeny ; Porifera/classification/*genetics ; Species Specificity ; }, abstract = {Resolving the relationships between the major lineages in the animal tree of life is necessary to understand the origin and evolution of key animal traits. Sponges, characterized by their simple body plan, were traditionally considered the sister group of all other animal lineages, implying a gradual increase in animal complexity from unicellularity to complex multicellularity. However, the availability of genomic data has sparked tremendous controversy as some phylogenomic studies support comb jellies taking this position, requiring secondary loss or independent origins of complex traits. Here we show that incorporating site-heterogeneous mixture models and recoding into partitioned phylogenomics alleviates systematic errors that hamper commonly-applied phylogenetic models. Testing on real datasets, we show a great improvement in model-fit that attenuates branching artefacts induced by systematic error. We reanalyse key datasets and show that partitioned phylogenomics does not support comb jellies as sister to other animals at either the supermatrix or partition-specific level.}, } @article {pmid33728391, year = {2021}, author = {Ji, S and Guvendiren, M}, title = {Complex 3D bioprinting methods.}, journal = {APL bioengineering}, volume = {5}, number = {1}, pages = {011508}, pmid = {33728391}, issn = {2473-2877}, abstract = {3D bioprinting technology is evolving in complexity to enable human-scale, high-resolution, and multi-cellular constructs to better mimic the native tissue microenvironment. The ultimate goal is to achieve necessary complexity in the bioprinting process to biomanufacture fully-functional tissues and organs to address organ shortage and lack of patient-specific disease models. In this Review, we presented an in-depth overview of complex 3D bioprinting approaches including evolution of complex bioprinting, from simple gel-casting approach to multi-material bioprinting to omnidirectional bioprinting approaches, and emerging bioprinting approaches, including 4D bioprinting and in situ bioprinting technologies.}, } @article {pmid33727612, year = {2021}, author = {Matriano, DM and Alegado, RA and Conaco, C}, title = {Detection of horizontal gene transfer in the genome of the choanoflagellate Salpingoeca rosetta.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {5993}, pmid = {33727612}, issn = {2045-2322}, mesh = {Choanoflagellata/classification/*genetics ; Computational Biology/methods ; Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genome ; Genomics/methods ; Molecular Sequence Annotation ; Phylogeny ; }, abstract = {Horizontal gene transfer (HGT), the movement of heritable materials between distantly related organisms, is crucial in eukaryotic evolution. However, the scale of HGT in choanoflagellates, the closest unicellular relatives of metazoans, and its possible roles in the evolution of animal multicellularity remains unexplored. We identified at least 175 candidate HGTs in the genome of the colonial choanoflagellate Salpingoeca rosetta using sequence-based tests. The majority of these were orthologous to genes in bacterial and microalgal lineages, yet displayed genomic features consistent with the rest of the S. rosetta genome-evidence of ancient acquisition events. Putative functions include enzymes involved in amino acid and carbohydrate metabolism, cell signaling, and the synthesis of extracellular matrix components. Functions of candidate HGTs may have contributed to the ability of choanoflagellates to assimilate novel metabolites, thereby supporting adaptation, survival in diverse ecological niches, and response to external cues that are possibly critical in the evolution of multicellularity in choanoflagellates.}, } @article {pmid33717121, year = {2021}, author = {Ramos-Martínez, E and Hernández-González, L and Ramos-Martínez, I and Pérez-Campos Mayoral, L and López-Cortés, GI and Pérez-Campos, E and Mayoral Andrade, G and Hernández-Huerta, MT and José, MV}, title = {Multiple Origins of Extracellular DNA Traps.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {621311}, pmid = {33717121}, issn = {1664-3224}, mesh = {Animals ; Biological Evolution ; Extracellular Traps/*metabolism ; Humans ; Immunity, Innate ; Neutrophils/*immunology ; Phylogeny ; }, abstract = {Extracellular DNA traps (ETs) are evolutionarily conserved antimicrobial mechanisms present in protozoa, plants, and animals. In this review, we compare their similarities in species of different taxa, and put forward the hypothesis that ETs have multiple origins. Our results are consistent with a process of evolutionary convergence in multicellular organisms through the application of a congruency test. Furthermore, we discuss why multicellularity is related to the presence of a mechanism initiating the formation of ETs.}, } @article {pmid33711511, year = {2021}, author = {Vijg, J}, title = {From DNA damage to mutations: All roads lead to aging.}, journal = {Ageing research reviews}, volume = {68}, number = {}, pages = {101316}, pmid = {33711511}, issn = {1872-9649}, support = {U01 HL145560/HL/NHLBI NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; P30 AG013319/AG/NIA NIH HHS/United States ; U01 ES029519/ES/NIEHS NIH HHS/United States ; U19 AG056278/AG/NIA NIH HHS/United States ; P30 AG038072/AG/NIA NIH HHS/United States ; P01 AG017242/AG/NIA NIH HHS/United States ; }, mesh = {Aging/genetics ; Animals ; *DNA Damage ; *DNA Repair/genetics ; Humans ; Mutagenesis ; Mutation ; }, abstract = {Damage to the repository of genetic information in cells has plagued life since its very beginning 3-4 billion years ago. Initially, in the absence of an ozone layer, especially damage from solar UV radiation must have been frequent, with other sources, most notably endogenous sources related to cell metabolism, gaining in importance over time. To cope with this high frequency of damage to the increasingly long DNA molecules that came to encode the growing complexity of cellular functions in cells, DNA repair evolved as one of the earliest genetic traits. Then as now, errors during the repair of DNA damage generated mutations, which provide the substrate for evolution by natural selection. With the emergence of multicellular organisms also the soma became a target of DNA damage and mutations. In somatic cells selection against the adverse effects of DNA damage is greatly diminished, especially in postmitotic cells after the age of first reproduction. Based on an abundance of evidence, DNA damage is now considered as the single most important driver of the degenerative processes that collectively cause aging. Here I will first briefly review the evidence for DNA damage as a cause of aging since the beginning of life. Then, after discussing the possible direct adverse effects of DNA damage and its cellular responses, I will provide an overview of the considerable progress that has recently been made in analyzing a major consequence of DNA damage in humans and other complex organisms: somatic mutations and the resulting genome mosaicism. Recent advances in studying somatic mutagenesis and genome mosaicism in different human and animal tissues will be discussed with a focus on the possible mechanisms through which loss of DNA sequence integrity could cause age-related functional decline and disease.}, } @article {pmid33690952, year = {2021}, author = {Darveau, RP and Curtis, MA}, title = {Oral biofilms revisited: A novel host tissue of bacteriological origin.}, journal = {Periodontology 2000}, volume = {86}, number = {1}, pages = {8-13}, doi = {10.1111/prd.12374}, pmid = {33690952}, issn = {1600-0757}, support = {MR/J011118/1/MRC_/Medical Research Council/United Kingdom ; MR/P012175/2/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Biofilms ; *Dental Plaque ; Gingiva ; Humans ; *Periodontitis ; }, abstract = {The central theme of this volume of Periodontology 2000 is that the microbial dental plaque biofilm, specifically the subgingival dental plaque biofilm, mimics a human tissue in both structure and function. As a basis for this assertion we use the definition of a tissue as an aggregate of similar cells and cell products forming a defined structure with a specific function, in a multicellular organism. Accordingly, we propose that the dental plaque biofilm represents an acquired human tissue largely of bacterial origin that maintains the health of gingival tissue. Furthermore, we acknowledge that disease can be defined as a deviation from the normal structure or an interruption to the function of any body part, organ, or system, and that is manifested by a characteristic set of symptoms and signs whose etiology, pathology, and prognosis may be known or unknown. Therefore, in this volume we present the concept that periodontitis is a disruption of the normal function of the healthy subgingival plaque biofilm with concomitant disruption to its functional properties in relation to innate defense surveillance and tissue maintenance, leading to excessive, deregulated inflammation and tissue destruction.}, } @article {pmid33683515, year = {2021}, author = {Ben-David, Y and Weihs, D}, title = {Modeling force application configurations and morphologies required for cancer cell invasion.}, journal = {Biomechanics and modeling in mechanobiology}, volume = {20}, number = {3}, pages = {1187-1194}, pmid = {33683515}, issn = {1617-7940}, support = {3-17427//Ministry of Science and Technology, Israel (IL)/ ; Polak Fund for Applied Research//Technion-Israel Institute of Technology/ ; }, mesh = {Biomechanical Phenomena/physiology ; Computer Simulation ; Elastic Modulus ; Finite Element Analysis ; Humans ; *Models, Biological ; Neoplasm Invasiveness ; Neoplasms/*pathology ; }, abstract = {We show that cell-applied, normal mechanical stresses are required for cells to penetrate into soft substrates, matching experimental observations in invasive cancer cells, while in-plane traction forces alone reproduce observations in non-cancer/noninvasive cells. Mechanobiological interactions of cells with their microenvironment drive migration and cancer invasion. We have previously shown that invasive cancer cells forcefully and rapidly push into impenetrable, physiological stiffness gels and indent them to cell-scale depths (up to 10 μm); normal, noninvasive cells indent at most to 0.7 μm. Significantly indenting cells signpost increased cancer invasiveness and higher metastatic risk in vitro and in vivo, as verified experimentally in different cancer types, yet the underlying cell-applied, force magnitudes and configurations required to produce the cell-scale gel indentations have yet to be evaluated. Hence, we have developed finite element models of forces applied onto soft, impenetrable gels using experimental cell/gel morphologies, gel mechanics, and force magnitudes. We show that in-plane traction forces can only induce small-scale indentations in soft gels (< 0.7 μm), matching experiments with various single, normal cells. Addition of a normal force (on the scale of experimental traction forces) produced cell-scale indentations that matched observations in invasive cancer cells. We note that normal stresses (force and area) determine the indentation depth, while contact area size and morphology have a minor effect, explaining the origin of experimentally observed cell morphologies. We have thus revealed controlling features facilitating invasive indentations by single cancer cells, which will allow application of our model to complex problems, such as multicellular systems.}, } @article {pmid33678014, year = {2021}, author = {Pen, I and Flatt, T}, title = {Asymmetry, division of labour and the evolution of ageing in multicellular organisms.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1823}, pages = {20190729}, pmid = {33678014}, issn = {1471-2970}, mesh = {*Aging ; Animals ; *Biological Evolution ; *Cell Differentiation ; *Cell Division ; Germ Cells/physiology ; Insecta/*physiology ; Models, Biological ; }, abstract = {Between the 1930s and 1960s, evolutionary geneticists worked out the basic principles of why organisms age. Despite much progress in the evolutionary biology of ageing since that time, however, many puzzles remain. The perhaps most fundamental of these is the question of which organisms should exhibit senescence and which should not (or which should age rapidly and which should not). The evolutionary origin of ageing from a non-senescent state has been conceptually framed, for example, in terms of the separation between germ-line and soma, the distinction between parents and their offspring, and-in unicellular organisms-the unequal distribution of cellular damage at cell division. These ideas seem to be closely related to the concept of 'division of labour' between reproduction and somatic maintenance. Here, we review these concepts and develop a toy model to explore the importance of such asymmetries for the evolution of senescence. We apply our model to the simplest case of a multicellular system: an organism consisting of two totipotent cells. Notably, we find that in organisms which reproduce symmetrically and partition damage equally, senescence is still able to evolve, contrary to previous claims. Our results might have some bearing on understanding the origin of the germ-line-soma separation and the evolution of senescence in multicellular organisms and in colonial species consisting of multiple types of individuals, such as, for example, eusocial insects with their different castes. This article is part of the theme issue 'Ageing and sociality: why, when and how does sociality change ageing patterns?'}, } @article {pmid33677158, year = {2021}, author = {Li, B and Tian, Y and Wen, H and Qi, X and Wang, L and Zhang, J and Li, J and Dong, X and Zhang, K and Li, Y}, title = {Systematic identification and expression analysis of the Sox gene family in spotted sea bass (Lateolabrax maculatus).}, journal = {Comparative biochemistry and physiology. Part D, Genomics & proteomics}, volume = {38}, number = {}, pages = {100817}, doi = {10.1016/j.cbd.2021.100817}, pmid = {33677158}, issn = {1878-0407}, mesh = {Animals ; Bass/*genetics ; Fish Proteins/*genetics ; Multigene Family ; Phylogeny ; SOX Transcription Factors/*genetics ; Transcriptome ; }, abstract = {The Sox gene family encodes a set of transcription factors characterized by a conserved Sry-related high mobility group (HMG)-box domain, which performs a series of essential biological functions in diverse tissues and developmental processes. In this study, the Sox gene family was systematically characterized in spotted sea bass (Lateolabrax maculatus). A total of 26 Sox genes were identified and classified into eight subfamilies, namely, SoxB1, SoxB2, SoxC, SoxD, SoxE, SoxF, SoxH and SoxK. The phylogenetic relationship, exon-intron and domain structure analyses supported their annotation and classification. Comparison of gene copy numbers and chromosome locations among different species indicated that except tandem duplicated paralogs of Sox17/Sox32, duplicated Sox genes in spotted sea bass were generated from teleost-specific whole genome duplication during evolution. In addition, qRT-PCR was performed to detect the expression profiles of Sox genes during development and adulthood. The results showed that the expression of 16 out of 26 Sox genes was induced dramatically at different starting points after the multicellular stage, which is consistent with embryogenesis. At the early stage of sex differentiation, 9 Sox genes exhibited sexually dimorphic expression patterns, among which Sox3, Sox19 and Sox6b showed the most significant ovary-biased expression. Moreover, the distinct expression pattern of Sox genes was observed in different adult tissues. Our results provide a fundamental resource for further investigating the functions of Sox genes in embryonic processes, sex determination and differentiation as well as controlling the homeostasis of adult tissues in spotted sea bass.}, } @article {pmid33675395, year = {2021}, author = {Jong, LW and Fujiwara, T and Hirooka, S and Miyagishima, SY}, title = {Cell size for commitment to cell division and number of successive cell divisions in cyanidialean red algae.}, journal = {Protoplasma}, volume = {258}, number = {5}, pages = {1103-1118}, pmid = {33675395}, issn = {1615-6102}, support = {17H01446, 20H00477//Japan Society for the Promotion of Science (JP)/ ; 19J13366//Japan Society for the Promotion of Science/ ; }, mesh = {Biological Evolution ; Cell Division ; Cell Size ; *Chlorophyta ; *Rhodophyta ; }, abstract = {Several eukaryotic cell lineages proliferate by multiple fission cell cycles, during which cells grow to manyfold of their original size, then undergo several rounds of cell division without intervening growth. A previous study on volvocine green algae, including both unicellular and multicellular (colonial) species, showed a correlation between the minimum number of successive cell divisions without intervening cellular growth, and the threshold cell size for commitment to the first round of successive cell divisions: two times the average newly born daughter cell volume for unicellular Chlamydomonas reinhardtii, four times for four-celled Tetrabaena socialis, in which each cell in the colony produces a daughter colony by two successive cell divisions, and eight times for the eight-celled Gonium pectorale, in which each cell produces a daughter colony by three successive cell divisions. To assess whether this phenomenon is also applicable to other lineages, we have characterized cyanidialean red algae, namely, Cyanidioschyzon merolae, which proliferates by binary fission, as well as Cyanidium caldarium and Galdieria sulphuraria, which form up to four and 32 daughter cells (autospores), respectively, in a mother cell before hatching out. The result shows that there is also a correlation between the number of successive cell divisions and the threshold cell size for cell division or the first round of the successive cell divisions. In both C. merolae and C. caldarium, the cell size checkpoint for cell division(s) exists in the G1-phase, as previously shown in volvocine green algae. When C. merolae cells were arrested in the G1-phase and abnormally enlarged by conditional depletion of CDKA, the cells underwent two or more successive cell divisions without intervening cellular growth after recovery of CDKA, similarly to C. caldarium and G. sulphuraria. These results suggest that the threshold size for cell division is a major factor in determining the number of successive cell divisions and that evolutionary changes in the mechanism of cell size monitoring resulted in a variation of multiple fission cell cycle in eukaryotic algae.}, } @article {pmid33672596, year = {2021}, author = {Ye, M and Wilhelm, M and Gentschev, I and Szalay, A}, title = {A Modified Limiting Dilution Method for Monoclonal Stable Cell Line Selection Using a Real-Time Fluorescence Imaging System: A Practical Workflow and Advanced Applications.}, journal = {Methods and protocols}, volume = {4}, number = {1}, pages = {}, pmid = {33672596}, issn = {2409-9279}, support = {82-5495702//Hope Realized Medical Foundation/ ; }, abstract = {Stable cell lines are widely used in laboratory research and pharmaceutical industry. They are mainly applied in recombinant protein and antibody productions, gene function studies, drug screens, toxicity assessments, and for cancer therapy investigation. There are two types of cell lines, polyclonal and monoclonal origin, that differ regarding their homogeneity and heterogeneity. Generating a high-quality stable cell line, which can grow continuously and carry a stable genetic modification without alteration is very important for most studies, because polyclonal cell lines of multicellular origin can be highly variable and unstable and lead to inconclusive experimental results. The most commonly used technologies of single cell originate monoclonal stable cell isolation in laboratory are fluorescence-activated cell sorting (FACS) sorting and limiting dilution cloning. Here, we describe a modified limiting dilution method of monoclonal stable cell line selection using the real-time fluorescence imaging system IncuCyte[®]S3.}, } @article {pmid33671243, year = {2021}, author = {Rathor, P and Borza, T and Stone, S and Tonon, T and Yurgel, S and Potin, P and Prithiviraj, B}, title = {A Novel Protein from Ectocarpus sp. Improves Salinity and High Temperature Stress Tolerance in Arabidopsis thaliana.}, journal = {International journal of molecular sciences}, volume = {22}, number = {4}, pages = {}, pmid = {33671243}, issn = {1422-0067}, support = {1177546//Natural Sciences and Engineering Research Council of Canada/ ; ANR-10-BTBR-04//Agence Nationale de la Recherche/ ; }, mesh = {*Adaptation, Physiological/genetics ; Algal Proteins/chemistry/genetics/*metabolism ; Arabidopsis/*genetics/growth & development/*physiology ; Electrolytes/metabolism ; Escherichia coli/metabolism ; Gene Expression Regulation, Plant ; *Hot Temperature ; Phaeophyta/*metabolism ; Phylogeny ; Plants, Genetically Modified ; Promoter Regions, Genetic/genetics ; *Salinity ; Seedlings/genetics ; *Stress, Physiological/genetics ; Tobacco/metabolism ; }, abstract = {Brown alga Ectocarpus sp. belongs to Phaeophyceae, a class of macroalgae that evolved complex multicellularity. Ectocarpus sp. is a dominant seaweed in temperate regions, abundant mostly in the intertidal zones, an environment with high levels of abiotic stresses. Previous transcriptomic analysis of Ectocarpus sp. revealed several genes consistently induced by various abiotic stresses; one of these genes is Esi0017_0056, which encodes a protein with unknown function. Bioinformatics analyses indicated that the protein encoded by Esi0017_0056 is soluble and monomeric. The protein was successfully expressed in Escherichia coli,Arabidopsis thaliana and Nicotiana benthamiana. In A. thaliana the gene was expressed under constitutive and stress inducible promoters which led to improved tolerance to high salinity and temperature stresses. The expression of several key abiotic stress-related genes was studied in transgenic and wild type A. thaliana by qPCR. Expression analysis revealed that genes involved in ABA-induced abiotic stress tolerance, K[+] homeostasis, and chaperon activities were significantly up-regulated in the transgenic line. This study is the first report in which an unknown function Ectocarpus sp. gene, highly responsive to abiotic stresses, was successfully expressed in A. thaliana, leading to improved tolerance to salt and temperature stress.}, } @article {pmid33668665, year = {2021}, author = {Saydé, T and El Hamoui, O and Alies, B and Gaudin, K and Lespes, G and Battu, S}, title = {Biomaterials for Three-Dimensional Cell Culture: From Applications in Oncology to Nanotechnology.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {33668665}, issn = {2079-4991}, support = {2018-1R10128//Conseil Régional Aquitaine/ ; }, abstract = {Three-dimensional cell culture has revolutionized cellular biology research and opened the door to novel discoveries in terms of cellular behavior and response to microenvironment stimuli. Different types of 3D culture exist today, including hydrogel scaffold-based models, which possess a complex structure mimicking the extracellular matrix. These hydrogels can be made of polymers (natural or synthetic) or low-molecular weight gelators that, via the supramolecular assembly of molecules, allow the production of a reproducible hydrogel with tunable mechanical properties. When cancer cells are grown in this type of hydrogel, they develop into multicellular tumor spheroids (MCTS). Three-dimensional (3D) cancer culture combined with a complex microenvironment that consists of a platform to study tumor development and also to assess the toxicity of physico-chemical entities such as ions, molecules or particles. With the emergence of nanoparticles of different origins and natures, implementing a reproducible in vitro model that consists of a bio-indicator for nano-toxicity assays is inevitable. However, the maneuver process of such a bio-indicator requires the implementation of a repeatable system that undergoes an exhaustive follow-up. Hence, the biggest challenge in this matter is the reproducibility of the MCTS and the associated full-scale characterization of this system's components.}, } @article {pmid33657376, year = {2021}, author = {Wang, J and Sun, H and Jiang, M and Li, J and Zhang, P and Chen, H and Mei, Y and Fei, L and Lai, S and Han, X and Song, X and Xu, S and Chen, M and Ouyang, H and Zhang, D and Yuan, GC and Guo, G}, title = {Tracing cell-type evolution by cross-species comparison of cell atlases.}, journal = {Cell reports}, volume = {34}, number = {9}, pages = {108803}, doi = {10.1016/j.celrep.2021.108803}, pmid = {33657376}, issn = {2211-1247}, mesh = {Animals ; Caenorhabditis elegans/genetics/metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; *Cell Lineage ; Ciona intestinalis/genetics/metabolism ; Databases, Genetic ; *Evolution, Molecular ; *Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genomics ; Humans ; Mice ; Muscle Cells/classification/*metabolism ; Neurons/classification/*metabolism ; *Single-Cell Analysis ; Species Specificity ; Transcription Factors/*genetics/metabolism ; *Transcriptome ; Zebrafish/genetics/metabolism ; Zebrafish Proteins/genetics/metabolism ; }, abstract = {Cell types are the basic building units of multicellular life, with extensive diversities. The evolution of cell types is a crucial layer of comparative cell biology but is thus far not comprehensively studied. We define a compendium of cell atlases using single-cell RNA-seq (scRNA-seq) data from seven animal species and construct a cross-species cell-type evolutionary hierarchy. We present a roadmap for the origin and diversity of major cell categories and find that muscle and neuron cells are conserved cell types. Furthermore, we identify a cross-species transcription factor (TF) repertoire that specifies major cell categories. Overall, our study reveals conservation and divergence of cell types during animal evolution, which will further expand the landscape of comparative genomics.}, } @article {pmid33656551, year = {2021}, author = {Yang, H and Shi, X and Chen, C and Hou, J and Ji, T and Cheng, J and Birchler, JA}, title = {Predominantly inverse modulation of gene expression in genomically unbalanced disomic haploid maize.}, journal = {The Plant cell}, volume = {33}, number = {4}, pages = {901-916}, pmid = {33656551}, issn = {1532-298X}, mesh = {Chromosomes, Plant ; Dosage Compensation, Genetic ; *Gene Expression Regulation, Plant ; Genes, Plant ; Genome, Plant ; *Haploidy ; Sequence Analysis, RNA ; Zea mays/*genetics ; }, abstract = {The phenotypic consequences of the addition or subtraction of part of a chromosome is more severe than changing the dosage of the whole genome. By crossing diploid trisomies to a haploid inducer, we identified 17 distal segmental haploid disomies that cover ∼80% of the maize genome. Disomic haploids provide a level of genomic imbalance that is not ordinarily achievable in multicellular eukaryotes, allowing the impact to be stronger and more easily studied. Transcriptome size estimates revealed that a few disomies inversely modulate most of the transcriptome. Based on RNA sequencing, the expression levels of genes located on the varied chromosome arms (cis) in disomies ranged from being proportional to chromosomal dosage (dosage effect) to showing dosage compensation with no expression change with dosage. For genes not located on the varied chromosome arm (trans), an obvious trans-acting effect can be observed, with the majority showing a decreased modulation (inverse effect). The extent of dosage compensation of varied cis genes correlates with the extent of trans inverse effects across the 17 genomic regions studied. The results also have implications for the role of stoichiometry in gene expression, the control of quantitative traits, and the evolution of dosage-sensitive genes.}, } @article {pmid33624753, year = {2021}, author = {Junqueira Alves, C and Silva Ladeira, J and Hannah, T and Pedroso Dias, RJ and Zabala Capriles, PV and Yotoko, K and Zou, H and Friedel, RH}, title = {Evolution and Diversity of Semaphorins and Plexins in Choanoflagellates.}, journal = {Genome biology and evolution}, volume = {13}, number = {3}, pages = {}, pmid = {33624753}, issn = {1759-6653}, support = {R01 NS092735/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Axon Guidance ; Biodiversity ; Biological Evolution ; Cell Adhesion Molecules/chemistry/*genetics/metabolism ; Choanoflagellata/classification/*genetics/*metabolism ; Ligands ; Models, Molecular ; Nerve Tissue Proteins/chemistry/*genetics/metabolism ; Phylogeny ; Protein Conformation ; Protein Domains ; Receptors, Cell Surface/genetics ; Semaphorins/*genetics/*metabolism ; }, abstract = {Semaphorins and plexins are cell surface ligand/receptor proteins that affect cytoskeletal dynamics in metazoan cells. Interestingly, they are also present in Choanoflagellata, a class of unicellular heterotrophic flagellates that forms the phylogenetic sister group to Metazoa. Several members of choanoflagellates are capable of forming transient colonies, whereas others reside solitary inside exoskeletons; their molecular diversity is only beginning to emerge. Here, we surveyed genomics data from 22 choanoflagellate species and detected semaphorin/plexin pairs in 16 species. Choanoflagellate semaphorins (Sema-FN1) contain several domain features distinct from metazoan semaphorins, including an N-terminal Reeler domain that may facilitate dimer stabilization, an array of fibronectin type III domains, a variable serine/threonine-rich domain that is a potential site for O-linked glycosylation, and a SEA domain that can undergo autoproteolysis. In contrast, choanoflagellate plexins (Plexin-1) harbor a domain arrangement that is largely identical to metazoan plexins. Both Sema-FN1 and Plexin-1 also contain a short homologous motif near the C-terminus, likely associated with a shared function. Three-dimensional molecular models revealed a highly conserved structural architecture of choanoflagellate Plexin-1 as compared to metazoan plexins, including similar predicted conformational changes in a segment that is involved in the activation of the intracellular Ras-GAP domain. The absence of semaphorins and plexins in several choanoflagellate species did not appear to correlate with unicellular versus colonial lifestyle or ecological factors such as fresh versus salt water environment. Together, our findings support a conserved mechanism of semaphorin/plexin proteins in regulating cytoskeletal dynamics in unicellular and multicellular organisms.}, } @article {pmid33622124, year = {2021}, author = {Evans, SD and Droser, ML and Erwin, DH}, title = {Developmental processes in Ediacara macrofossils.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1945}, pages = {20203055}, pmid = {33622124}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; Biota ; *Fossils ; Nervous System ; Phylogeny ; }, abstract = {The Ediacara Biota preserves the oldest fossil evidence of abundant, complex metazoans. Despite their significance, assigning individual taxa to specific phylogenetic groups has proved problematic. To better understand these forms, we identify developmentally controlled characters in representative taxa from the Ediacaran White Sea assemblage and compare them with the regulatory tools underlying similar traits in modern organisms. This analysis demonstrates that the genetic pathways for multicellularity, axial polarity, musculature, and a nervous system were likely present in some of these early animals. Equally meaningful is the absence of evidence for major differentiation of macroscopic body units, including distinct organs, localized sensory machinery or appendages. Together these traits help to better constrain the phylogenetic position of several key Ediacara taxa and inform our views of early metazoan evolution. An apparent lack of heads with concentrated sensory machinery or ventral nerve cords in such taxa supports the hypothesis that these evolved independently in disparate bilaterian clades.}, } @article {pmid33622103, year = {2021}, author = {Ros-Rocher, N and Pérez-Posada, A and Leger, MM and Ruiz-Trillo, I}, title = {The origin of animals: an ancestral reconstruction of the unicellular-to-multicellular transition.}, journal = {Open biology}, volume = {11}, number = {2}, pages = {200359}, pmid = {33622103}, issn = {2046-2441}, mesh = {Alveolata/cytology/genetics ; Animals ; *Evolution, Molecular ; Phylogeny ; }, abstract = {How animals evolved from a single-celled ancestor, transitioning from a unicellular lifestyle to a coordinated multicellular entity, remains a fascinating question. Key events in this transition involved the emergence of processes related to cell adhesion, cell-cell communication and gene regulation. To understand how these capacities evolved, we need to reconstruct the features of both the last common multicellular ancestor of animals and the last unicellular ancestor of animals. In this review, we summarize recent advances in the characterization of these ancestors, inferred by comparative genomic analyses between the earliest branching animals and those radiating later, and between animals and their closest unicellular relatives. We also provide an updated hypothesis regarding the transition to animal multicellularity, which was likely gradual and involved the use of gene regulatory mechanisms in the emergence of early developmental and morphogenetic plans. Finally, we discuss some new avenues of research that will complement these studies in the coming years.}, } @article {pmid33617837, year = {2021}, author = {Debets, VE and Janssen, LMC and Storm, C}, title = {Enhanced persistence and collective migration in cooperatively aligning cell clusters.}, journal = {Biophysical journal}, volume = {120}, number = {8}, pages = {1483-1497}, pmid = {33617837}, issn = {1542-0086}, mesh = {Attention ; Biophysics ; Cell Movement ; Humans ; *Neoplasms ; }, abstract = {Most cells possess the capacity to locomote. Alone or collectively, this allows them to adapt, to rearrange, and to explore their surroundings. The biophysical characterization of such motile processes, in health and in disease, has so far focused mostly on two limiting cases: single-cell motility on the one hand and the dynamics of confluent tissues such as the epithelium on the other. The in-between regime of clusters, composed of relatively few cells moving as a coherent unit, has received less attention. Such small clusters are, however, deeply relevant in development but also in cancer metastasis. In this work, we use cellular Potts models and analytical active matter theory to understand how the motility of small cell clusters changes with N, the number of cells in the cluster. Modeling and theory reveal our two main findings: cluster persistence time increases with N, whereas the intrinsic diffusivity decreases with N. We discuss a number of settings in which the motile properties of more complex clusters can be analytically understood, revealing that the focusing effects of small-scale cooperation and cell-cell alignment can overcome the increased bulkiness and internal disorder of multicellular clusters to enhance overall migrational efficacy. We demonstrate this enhancement for small-cluster collective durotaxis, which is shown to proceed more effectively than for single cells. Our results may provide some novel, to our knowledge, insights into the connection between single-cell and large-scale collective motion and may point the way to the biophysical origins of the enhanced metastatic potential of small tumor cell clusters.}, } @article {pmid33615674, year = {2021}, author = {Bergero, R and Ellis, P and Haerty, W and Larcombe, L and Macaulay, I and Mehta, T and Mogensen, M and Murray, D and Nash, W and Neale, MJ and O'Connor, R and Ottolini, C and Peel, N and Ramsey, L and Skinner, B and Suh, A and Summers, M and Sun, Y and Tidy, A and Rahbari, R and Rathje, C and Immler, S}, title = {Meiosis and beyond - understanding the mechanistic and evolutionary processes shaping the germline genome.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {96}, number = {3}, pages = {822-841}, pmid = {33615674}, issn = {1469-185X}, mesh = {Biological Evolution ; Genome ; *Germ Cells ; *Meiosis/genetics ; Mutation ; }, abstract = {The separation of germ cell populations from the soma is part of the evolutionary transition to multicellularity. Only genetic information present in the germ cells will be inherited by future generations, and any molecular processes affecting the germline genome are therefore likely to be passed on. Despite its prevalence across taxonomic kingdoms, we are only starting to understand details of the underlying micro-evolutionary processes occurring at the germline genome level. These include segregation, recombination, mutation and selection and can occur at any stage during germline differentiation and mitotic germline proliferation to meiosis and post-meiotic gamete maturation. Selection acting on germ cells at any stage from the diploid germ cell to the haploid gametes may cause significant deviations from Mendelian inheritance and may be more widespread than previously assumed. The mechanisms that affect and potentially alter the genomic sequence and allele frequencies in the germline are pivotal to our understanding of heritability. With the rise of new sequencing technologies, we are now able to address some of these unanswered questions. In this review, we comment on the most recent developments in this field and identify current gaps in our knowledge.}, } @article {pmid33603764, year = {2021}, author = {Castañeda, V and González, EM and Wienkoop, S}, title = {Phloem Sap Proteins Are Part of a Core Stress Responsive Proteome Involved in Drought Stress Adjustment.}, journal = {Frontiers in plant science}, volume = {12}, number = {}, pages = {625224}, pmid = {33603764}, issn = {1664-462X}, abstract = {During moderate drought stress, plants can adjust by changes in the protein profiles of the different organs. Plants transport and modulate extracellular stimuli local and systemically through commonly induced inter- and intracellular reactions. However, most proteins are frequently considered, cell and organelle specific. Hence, while signaling molecules and peptides can travel systemically throughout the whole plant, it is not clear, whether protein isoforms may exist ubiquitously across organs, and what function those may have during drought regulation. By applying shotgun proteomics, we extracted a core proteome of 92 identical protein isoforms, shared ubiquitously amongst several Medicago truncatula tissues, including roots, phloem sap, petioles, and leaves. We investigated their relative distribution across the different tissues and their response to moderate drought stress. In addition, we functionally compared this plant core stress responsive proteome with the organ-specific proteomes. Our study revealed plant ubiquitous protein isoforms, mainly related to redox homeostasis and signaling and involved in protein interaction networks across the whole plant. Furthermore, about 90% of these identified core protein isoforms were significantly involved in drought stress response, indicating a crucial role of the core stress responsive proteome (CSRP) in the plant organ cross-communication, important for a long-distance stress-responsive network. Besides, the data allowed for a comprehensive characterization of the phloem proteome, revealing new insights into its function. For instance, CSRP protein levels involved in stress and redox are relatively more abundant in the phloem compared to the other tissues already under control conditions. This suggests a major role of the phloem in stress protection and antioxidant activity enabling the plants metabolic maintenance and rapid response upon moderate stress. We anticipate our study to be a starting point for future investigations of the role of the core plant proteome. Under an evolutionary perspective, CSRP would enable communication of different cells with each other and the environment being crucial for coordinated stress response of multicellular organisms.}, } @article {pmid33602485, year = {2021}, author = {McKenna, KZ and Wagner, GP and Cooper, KL}, title = {A developmental perspective of homology and evolutionary novelty.}, journal = {Current topics in developmental biology}, volume = {141}, number = {}, pages = {1-38}, doi = {10.1016/bs.ctdb.2020.12.001}, pmid = {33602485}, issn = {1557-8933}, mesh = {Animals ; *Biological Evolution ; Crustacea/anatomy & histology ; Developmental Biology ; *Gene Regulatory Networks ; Genes, Homeobox ; Genitalia, Male/physiology ; Homeodomain Proteins/genetics ; Insecta ; Male ; Pelvis ; Phylogeny ; Transcription Factors/genetics ; Vertebrates/*anatomy & histology ; *Wings, Animal/anatomy & histology ; }, abstract = {The development and evolution of multicellular body plans is complex. Many distinct organs and body parts must be reproduced at each generation, and those that are traceable over long time scales are considered homologous. Among the most pressing and least understood phenomena in evolutionary biology is the mode by which new homologs, or "novelties" are introduced to the body plan and whether the developmental changes associated with such evolution deserve special treatment. In this chapter, we address the concepts of homology and evolutionary novelty through the lens of development. We present a series of case studies, within insects and vertebrates, from which we propose a developmental model of multicellular organ identity. With this model in hand, we make predictions regarding the developmental evolution of body plans and highlight the need for more integrative analysis of developing systems.}, } @article {pmid33600401, year = {2021}, author = {Goldberg, Y and Friedman, J}, title = {Positive interactions within and between populations decrease the likelihood of evolutionary rescue.}, journal = {PLoS computational biology}, volume = {17}, number = {2}, pages = {e1008732}, pmid = {33600401}, issn = {1553-7358}, mesh = {*Adaptation, Physiological ; Animals ; *Biological Evolution ; Computational Biology ; Computer Simulation ; *Ecosystem ; Extinction, Biological ; Humans ; *Models, Biological ; Phenotype ; Probability ; Selection, Genetic ; Stress, Physiological ; *Symbiosis ; }, abstract = {Positive interactions, including intraspecies cooperation and interspecies mutualisms, play crucial roles in shaping the structure and function of many ecosystems, ranging from plant communities to the human microbiome. While the evolutionary forces that form and maintain positive interactions have been investigated extensively, the influence of positive interactions on the ability of species to adapt to new environments is still poorly understood. Here, we use numerical simulations and theoretical analyses to study how positive interactions impact the likelihood that populations survive after an environment deteriorates, such that survival in the new environment requires quick adaptation via the rise of new mutants-a scenario known as evolutionary rescue. We find that the probability of evolutionary rescue in populations engaged in positive interactions is reduced significantly. In cooperating populations, this reduction is largely due to the fact that survival may require at least a minimal number of individuals, meaning that adapted mutants must arise and spread before the population declines below this threshold. In mutualistic populations, the rescue probability is decreased further due to two additional effects-the need for both mutualistic partners to adapt to the new environment, and competition between the two species. Finally, we show that the presence of cheaters reduces the likelihood of evolutionary rescue even further, making it extremely unlikely. These results indicate that while positive interactions may be beneficial in stable environments, they can hinder adaptation to changing environments and thereby elevate the risk of population collapse. Furthermore, these results may hint at the selective pressures that drove co-dependent unicellular species to form more adaptable organisms able to differentiate into multiple phenotypes, including multicellular life.}, } @article {pmid33593190, year = {2021}, author = {He, S and Sieksmeyer, T and Che, Y and Mora, MAE and Stiblik, P and Banasiak, R and Harrison, MC and Šobotník, J and Wang, Z and Johnston, PR and McMahon, DP}, title = {Evidence for reduced immune gene diversity and activity during the evolution of termites.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1945}, pages = {20203168}, pmid = {33593190}, issn = {1471-2954}, mesh = {Animals ; Biological Evolution ; *Cockroaches ; *Isoptera/genetics ; Phylogeny ; Social Behavior ; }, abstract = {The evolution of biological complexity is associated with the emergence of bespoke immune systems that maintain and protect organism integrity. Unlike the well-studied immune systems of cells and individuals, little is known about the origins of immunity during the transition to eusociality, a major evolutionary transition comparable to the evolution of multicellular organisms from single-celled ancestors. We aimed to tackle this by characterizing the immune gene repertoire of 18 cockroach and termite species, spanning the spectrum of solitary, subsocial and eusocial lifestyles. We find that key transitions in termite sociality are correlated with immune gene family contractions. In cross-species comparisons of immune gene expression, we find evidence for a caste-specific social defence system in termites, which appears to operate at the expense of individual immune protection. Our study indicates that a major transition in organismal complexity may have entailed a fundamental reshaping of the immune system optimized for group over individual defence.}, } @article {pmid33588307, year = {2021}, author = {Crawford, MA and Schmidt, WF and Broadhurst, CL and Wang, Y}, title = {Lipids in the origin of intracellular detail and speciation in the Cambrian epoch and the significance of the last double bond of docosahexaenoic acid in cell signaling.}, journal = {Prostaglandins, leukotrienes, and essential fatty acids}, volume = {166}, number = {}, pages = {102230}, doi = {10.1016/j.plefa.2020.102230}, pmid = {33588307}, issn = {1532-2823}, mesh = {Animals ; Brain/metabolism ; Carbon/metabolism ; Cell Membrane/metabolism ; Docosahexaenoic Acids/chemistry/*history/*metabolism ; *Electrons ; Fatty Acids, Unsaturated/chemistry/*history/*metabolism ; History, Ancient ; Humans ; Hydrogen/metabolism ; Intracellular Space/*metabolism ; Neurons/metabolism ; Retina/metabolism ; *Signal Transduction ; }, abstract = {One of the great unanswered biological questions is the absolute necessity of the polyunsaturated lipid docosahexaenoic acid (DHA; 22:6n-3) in retinal and neural tissues. Everything from the simple eye spot of dinoflagellates to cephalopods to every class of vertebrates uses DHA, yet it is abundant only in cold water marine food chains. Docosapentaenoic acids (DPAs; 22:5n-6 and especially 22:5n-3) are fairly plentiful in food chains yet cannot substitute for DHA. About 600 million years ago, multi-cellular, air breathing systems evolved rapidly and 32 phyla came into existence in a short geological time span; the "Cambrian Explosion". Eukaryotic intracellular detail requires cell membranes, which are constructed of complex lipids, and proteins. Proteins and nucleic acids would have been abundant during the first 2.5-5 billion years of anaerobic life but lipids, especially unsaturated fatty acids, would not. We hypothesize lipid biology was a key driver of the Cambrian Explosion, because it alone provides for compartmentalization and specialization within cells DHA has six methylene interrupted double bonds providing controlled electron flow at precise energy levels; this is essential for visual acuity and truthful execution of the neural pathways which make up our recollections, information processing and consciousness. The last double bond is critical for the evolution and function of the photoreceptor and neuronal and synaptic signaling systems. It completes a quantum mechanical device for the regulation of current flow with absolute signal precision based on electron tunneling (ET). DHA's methylene interruption distance is < 6 Å, making ET transfer between the π-orbitals feasible throughout the molecule. The possibility fails if one double bond is removed and replaced by a saturated bond as in the DPAs. The molecular biophysical foundation of neural signaling can also include the discrete pattern of paired spin states that arise in the DHA double bond and methylene regions. The complexity depends upon the number of C13 and H1 molecular sites in which spin states are coupled. Electron wave harmonics with entanglement and cohesion provide a mechanism for learning and memory, and power cognition and complex human brain functions.}, } @article {pmid33575354, year = {2021}, author = {Pourhasanzade, F and Sabzpoushan, SH}, title = {A New Mathematical Model for Controlling Tumor Growth Based on Microenvironment Acidity and Oxygen Concentration.}, journal = {BioMed research international}, volume = {2021}, number = {}, pages = {8886050}, pmid = {33575354}, issn = {2314-6141}, mesh = {Animals ; Humans ; Male ; Mice ; Mice, Nude ; Neoplasms/*metabolism ; Oxygen/*metabolism ; *Tumor Microenvironment/drug effects/physiology ; }, abstract = {Hypoxia and the pH level of the tumor microenvironment have a great impact on the treatment of tumors. Here, the tumor growth is controlled by regulating the oxygen concentration and the acidity of the tumor microenvironment by introducing a two-dimensional multiscale cellular automata model of avascular tumor growth. The spatiotemporal evolution of tumor growth and metabolic variations is modeled based on biological assumptions, physical structure, states of cells, and transition rules. Each cell is allocated to one of the following states: proliferating cancer, nonproliferating cancer, necrotic, and normal cells. According to the response of the microenvironmental conditions, each cell consumes/produces metabolic factors and updates its state based on some stochastic rules. The input parameters are compatible with cancer biology using experimental data. The effect of neighborhoods during mitosis and simulating spatial heterogeneity is studied by considering multicellular layer structure of tumor. A simple Darwinist mutation is considered by introducing a critical parameter (Nmm) that affects division probability of the proliferative tumor cells based on the microenvironmental conditions and cancer hallmarks. The results show that Nmm regulation has a significant influence on the dynamics of tumor growth, the growth fraction, necrotic fraction, and the concentration levels of the metabolic factors. The model not only is able to simulate the in vivo tumor growth quantitatively and qualitatively but also can simulate the concentration of metabolic factors, oxygen, and acidity graphically. The results show the spatial heterogeneity effects on the proliferation of cancer cells and the rest of the system. By increasing Nmm, tumor shrinkage and significant increasing in the oxygen concentration and the pH value of the tumor microenvironment are observed. The results demonstrate the model's ability, providing an essential tool for simulating different tumor evolution scenarios of a patient and reliable prediction of spatiotemporal progression of tumors for utilizing in personalized therapy.}, } @article {pmid33565083, year = {2021}, author = {Bustamante, DE and Yeon Won, B and Wynne, MJ and Cho, TO}, title = {Molecular and morphological analyses reveal new taxa additions to the tribe Streblocladieae (Rhodomelaceae, Rhodophyta).}, journal = {Journal of phycology}, volume = {57}, number = {3}, pages = {817-830}, doi = {10.1111/jpy.13144}, pmid = {33565083}, issn = {1529-8817}, mesh = {Evolution, Molecular ; Phylogeny ; *Rhodophyta ; }, abstract = {The recent segregation of 12 genera in the tribe Streblocladieae suggests that the taxonomy of some species belonging to Polysiphonia sensu lato is updated with the transfer and the proposal of new combinations. Accordingly, six new additions to the tribe Streblocladieae on the basis of morphological and molecular analyses are presented as a consequence of this new segregation. These additions include the description of the new species Carradoriella platensis sp. nov., the proposal of the following new combinations Eutrichosiphonia paniculata comb. nov., E. tapinocarpa comb. nov., and the reinstatement of Vertebrata curta, V. decipiens, and V. patersonis. Additionally, our morphological observations identified additional diagnostic features for two genera of the Streblocladieae. Carradoriella has branches with sexual reproductive structures arranged adaxially on branchlets, and the recently described Eutrichosiphonia has rhizoids with multicellular digitate haptera. Our study gives insights in regards to the distribution, the diagnostic features for delimiting genera morphologically, and the molecular evolutionary relationships in the Streblocladieae.}, } @article {pmid33561386, year = {2021}, author = {Prostak, SM and Robinson, KA and Titus, MA and Fritz-Laylin, LK}, title = {The actin networks of chytrid fungi reveal evolutionary loss of cytoskeletal complexity in the fungal kingdom.}, journal = {Current biology : CB}, volume = {31}, number = {6}, pages = {1192-1205.e6}, pmid = {33561386}, issn = {1879-0445}, support = {R01 GM122917/GM/NIGMS NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/*metabolism ; Actins/*metabolism ; Amphibians/microbiology ; Animals ; Chytridiomycota/*classification/*metabolism ; *Evolution, Molecular ; }, abstract = {Cells from across the eukaryotic tree use actin polymer networks for a wide variety of functions, including endocytosis, cytokinesis, and cell migration. Despite this functional conservation, the actin cytoskeleton has undergone significant diversification, highlighted by the differences in the actin networks of mammalian cells and yeast. Chytrid fungi diverged before the emergence of the Dikarya (multicellular fungi and yeast) and therefore provide a unique opportunity to study actin cytoskeletal evolution. Chytrids have two life stages: zoospore cells that can swim with a flagellum and sessile sporangial cells that, like multicellular fungi, are encased in a chitinous cell wall. Here, we show that zoospores of the amphibian-killing chytrid Batrachochytrium dendrobatidis (Bd) build dynamic actin structures resembling those of animal cells, including an actin cortex, pseudopods, and filopodia-like spikes. In contrast, Bd sporangia assemble perinuclear actin shells and actin patches similar to those of yeast. The use of specific small-molecule inhibitors indicate that nearly all of Bd's actin structures are dynamic and use distinct nucleators: although pseudopods and actin patches are Arp2/3 dependent, the actin cortex appears formin dependent and actin spikes require both nucleators. Our analysis of multiple chytrid genomes reveals actin regulators and myosin motors found in animals, but not dikaryotic fungi, as well as fungal-specific components. The presence of animal- and yeast-like actin cytoskeletal components in the genome combined with the intermediate actin phenotypes in Bd suggests that the simplicity of the yeast cytoskeleton may be due to evolutionary loss.}, } @article {pmid33550955, year = {2021}, author = {Ginsburg, S and Jablonka, E}, title = {Evolutionary transitions in learning and cognition.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190766}, pmid = {33550955}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Cognition/*physiology ; Learning/*physiology ; Phylogeny ; }, abstract = {We define a cognitive system as a system that can learn, and adopt an evolutionary-transition-oriented framework for analysing different types of neural cognition. This enables us to classify types of cognition and point to the continuities and discontinuities among them. The framework we use for studying evolutionary transitions in learning capacities focuses on qualitative changes in the integration, storage and use of neurally processed information. Although there are always grey areas around evolutionary transitions, we recognize five major neural transitions, the first two of which involve animals at the base of the phylogenetic tree: (i) the evolutionary transition from learning in non-neural animals to learning in the first neural animals; (ii) the transition to animals showing limited, elemental associative learning, entailing neural centralization and primary brain differentiation; (iii) the transition to animals capable of unlimited associative learning, which, on our account, constitutes sentience and entails hierarchical brain organization and dedicated memory and value networks; (iv) the transition to imaginative animals that can plan and learn through selection among virtual events; and (v) the transition to human symbol-based cognition and cultural learning. The focus on learning provides a unifying framework for experimental and theoretical studies of cognition in the living world. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550954, year = {2021}, author = {Jékely, G and Godfrey-Smith, P and Keijzer, F}, title = {Reafference and the origin of the self in early nervous system evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190764}, pmid = {33550954}, issn = {1471-2970}, mesh = {Animals ; Cnidaria/physiology ; Ctenophora/physiology ; Efferent Pathways/*physiology ; Nervous System/chemistry ; *Nervous System Physiological Phenomena ; Placozoa/physiology ; Porifera/physiology ; *Proprioception ; }, abstract = {Discussions of the function of early nervous systems usually focus on a causal flow from sensors to effectors, by which an animal coordinates its actions with exogenous changes in its environment. We propose, instead, that much early sensing was reafferent; it was responsive to the consequences of the animal's own actions. We distinguish two general categories of reafference-translocational and deformational-and use these to survey the distribution of several often-neglected forms of sensing, including gravity sensing, flow sensing and proprioception. We discuss sensing of these kinds in sponges, ctenophores, placozoans, cnidarians and bilaterians. Reafference is ubiquitous, as ongoing action, especially whole-body motility, will almost inevitably influence the senses. Corollary discharge-a pathway or circuit by which an animal tracks its own actions and their reafferent consequences-is not a necessary feature of reafferent sensing but a later-evolving mechanism. We also argue for the importance of reafferent sensing to the evolution of the body-self, a form of organization that enables an animal to sense and act as a single unit. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550952, year = {2021}, author = {Pezzulo, G and LaPalme, J and Durant, F and Levin, M}, title = {Bistability of somatic pattern memories: stochastic outcomes in bioelectric circuits underlying regeneration.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190765}, pmid = {33550952}, issn = {1471-2970}, mesh = {Animals ; *Cell Communication ; *Cognition ; Cognitive Science ; Electrophysiological Phenomena/physiology ; Models, Neurological ; Planarians/*physiology ; *Regeneration ; }, abstract = {Nervous systems' computational abilities are an evolutionary innovation, specializing and speed-optimizing ancient biophysical dynamics. Bioelectric signalling originated in cells' communication with the outside world and with each other, enabling cooperation towards adaptive construction and repair of multicellular bodies. Here, we review the emerging field of developmental bioelectricity, which links the field of basal cognition to state-of-the-art questions in regenerative medicine, synthetic bioengineering and even artificial intelligence. One of the predictions of this view is that regeneration and regulative development can restore correct large-scale anatomies from diverse starting states because, like the brain, they exploit bioelectric encoding of distributed goal states-in this case, pattern memories. We propose a new interpretation of recent stochastic regenerative phenotypes in planaria, by appealing to computational models of memory representation and processing in the brain. Moreover, we discuss novel findings showing that bioelectric changes induced in planaria can be stored in tissue for over a week, thus revealing that somatic bioelectric circuits in vivo can implement a long-term, re-writable memory medium. A consideration of the mechanisms, evolution and functionality of basal cognition makes novel predictions and provides an integrative perspective on the evolution, physiology and biomedicine of information processing in vivo. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550951, year = {2021}, author = {Göhde, R and Naumann, B and Laundon, D and Imig, C and McDonald, K and Cooper, BH and Varoqueaux, F and Fasshauer, D and Burkhardt, P}, title = {Choanoflagellates and the ancestry of neurosecretory vesicles.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190759}, pmid = {33550951}, issn = {1471-2970}, mesh = {*Biological Evolution ; Choanoflagellata/*physiology ; R-SNARE Proteins/*metabolism ; Synaptic Vesicles/*physiology ; }, abstract = {Neurosecretory vesicles are highly specialized trafficking organelles that store neurotransmitters that are released at presynaptic nerve endings and are, therefore, important for animal cell-cell signalling. Despite considerable anatomical and functional diversity of neurons in animals, the protein composition of neurosecretory vesicles in bilaterians appears to be similar. This similarity points towards a common evolutionary origin. Moreover, many putative homologues of key neurosecretory vesicle proteins predate the origin of the first neurons, and some even the origin of the first animals. However, little is known about the molecular toolkit of these vesicles in non-bilaterian animals and their closest unicellular relatives, making inferences about the evolutionary origin of neurosecretory vesicles extremely difficult. By comparing 28 proteins of the core neurosecretory vesicle proteome in 13 different species, we demonstrate that most of the proteins are present in unicellular organisms. Surprisingly, we find that the vesicular membrane-associated soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein synaptobrevin is localized to the vesicle-rich apical and basal pole in the choanoflagellate Salpingoeca rosetta. Our 3D vesicle reconstructions reveal that the choanoflagellates S. rosetta and Monosiga brevicollis exhibit a polarized and diverse vesicular landscape reminiscent of the polarized organization of chemical synapses that secrete the content of neurosecretory vesicles into the synaptic cleft. This study sheds light on the ancestral molecular machinery of neurosecretory vesicles and provides a framework to understand the origin and evolution of secretory cells, synapses and neurons. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550950, year = {2021}, author = {Levin, M and Keijzer, F and Lyon, P and Arendt, D}, title = {Uncovering cognitive similarities and differences, conservation and innovation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20200458}, pmid = {33550950}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Cognition/*physiology ; *Nervous System Physiological Phenomena ; }, abstract = {This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550949, year = {2021}, author = {Moroz, LL and Romanova, DY and Kohn, AB}, title = {Neural versus alternative integrative systems: molecular insights into origins of neurotransmitters.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190762}, pmid = {33550949}, issn = {1471-2970}, support = {R01 NS114491/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cell Communication/*physiology ; *Evolution, Molecular ; Neurotransmitter Agents/*chemistry ; Placozoa/physiology ; *Signal Transduction ; }, abstract = {Transmitter signalling is the universal chemical language of any nervous system, but little is known about its early evolution. Here, we summarize data about the distribution and functions of neurotransmitter systems in basal metazoans as well as outline hypotheses of their origins. We explore the scenario that neurons arose from genetically different populations of secretory cells capable of volume chemical transmission and integration of behaviours without canonical synapses. The closest representation of this primordial organization is currently found in Placozoa, disk-like animals with the simplest known cell composition but complex behaviours. We propose that injury-related signalling was the evolutionary predecessor for integrative functions of early transmitters such as nitric oxide, ATP, protons, glutamate and small peptides. By contrast, acetylcholine, dopamine, noradrenaline, octopamine, serotonin and histamine were recruited as canonical neurotransmitters relatively later in animal evolution, only in bilaterians. Ligand-gated ion channels often preceded the establishment of novel neurotransmitter systems. Moreover, lineage-specific diversification of neurotransmitter receptors occurred in parallel within Cnidaria and several bilaterian lineages, including acoels. In summary, ancestral diversification of secretory signal molecules provides unique chemical microenvironments for behaviour-driven innovations that pave the way to complex brain functions and elementary cognition. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550948, year = {2021}, author = {Arendt, D}, title = {Elementary nervous systems.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20200347}, pmid = {33550948}, issn = {1471-2970}, mesh = {Animals ; Behavior, Animal/*physiology ; *Biological Evolution ; *Body Size ; Cilia/*physiology ; Nerve Net/*physiology ; }, abstract = {The evolutionary origin of the nervous system has been a matter of long-standing debate. This is due to the different perspectives taken. Earlier studies addressed nervous system origins at the cellular level. They focused on the selective advantage of the first neuron in its local context, and considered vertical sensory-motor reflex arcs the first nervous system. Later studies emphasized the value of the nervous system at the tissue level. Rather than acting locally, early neurons were seen as part of an elementary nerve net that enabled the horizontal coordination of tissue movements. Opinions have also differed on the nature of effector cells. While most authors have favoured contractile systems, others see the key output of the incipient nervous system in the coordination of motile cilia, or the secretion of antimicrobial peptides. I will discuss these divergent views and explore how they can be validated by molecular and single-cell data. From this survey, possible consensus emerges: (i) the first manifestation of the nervous system likely was a nerve net, whereas specialized local circuits evolved later; (ii) different nerve nets may have evolved for the coordination of contractile or cilia-driven movements; (iii) all evolving nerve nets facilitated new forms of animal behaviour with increasing body size. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550946, year = {2021}, author = {Jékely, G}, title = {The chemical brain hypothesis for the origin of nervous systems.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190761}, pmid = {33550946}, issn = {1471-2970}, mesh = {*Biological Evolution ; Brain/*physiology ; Nervous System/*chemistry ; *Signal Transduction ; Synaptic Transmission/*physiology ; }, abstract = {In nervous systems, there are two main modes of transmission for the propagation of activity between cells. Synaptic transmission relies on close contact at chemical or electrical synapses while volume transmission is mediated by diffusible chemical signals and does not require direct contact. It is possible to wire complex neuronal networks by both chemical and synaptic transmission. Both types of networks are ubiquitous in nervous systems, leading to the question which of the two appeared first in evolution. This paper explores a scenario where chemically organized cellular networks appeared before synapses in evolution, a possibility supported by the presence of complex peptidergic signalling in all animals except sponges. Small peptides are ideally suited to link up cells into chemical networks. They have unlimited diversity, high diffusivity and high copy numbers derived from repetitive precursors. But chemical signalling is diffusion limited and becomes inefficient in larger bodies. To overcome this, peptidergic cells may have developed projections and formed synaptically connected networks tiling body surfaces and displaying synchronized activity with pulsatile peptide release. The advent of circulatory systems and neurohemal organs further reduced the constraint imposed on chemical signalling by diffusion. This could have contributed to the explosive radiation of peptidergic signalling systems in stem bilaterians. Neurosecretory centres in extant nervous systems are still predominantly chemically wired and coexist with the synaptic brain. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33542245, year = {2021}, author = {Grum-Grzhimaylo, AA and Bastiaans, E and van den Heuvel, J and Berenguer Millanes, C and Debets, AJM and Aanen, DK}, title = {Somatic deficiency causes reproductive parasitism in a fungus.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {783}, pmid = {33542245}, issn = {2041-1723}, mesh = {Cell Fusion ; DNA Mutational Analysis ; *Evolution, Molecular ; Fungal Proteins/*genetics/metabolism ; Gene Knockout Techniques ; Genes, Fungal/genetics ; Hyphae/*physiology ; Mutation ; Neurospora crassa/*physiology ; }, abstract = {Some multicellular organisms can fuse because mergers potentially provide mutual benefits. However, experimental evolution in the fungus Neurospora crassa has demonstrated that free fusion of mycelia favours cheater lineages, but the mechanism and evolutionary dynamics of this exploitation are unknown. Here we show, paradoxically, that all convergently evolved cheater lineages have similar fusion deficiencies. These mutants are unable to initiate fusion but retain access to wild-type mycelia that fuse with them. This asymmetry reduces cheater-mutant contributions to somatic substrate-bound hyphal networks, but increases representation of their nuclei in the aerial reproductive hyphae. Cheaters only benefit when relatively rare and likely impose genetic load reminiscent of germline senescence. We show that the consequences of somatic fusion can be unequally distributed among fusion partners, with the passive non-fusing partner profiting more. We discuss how our findings may relate to the extensive variation in fusion frequency of fungi found in nature.}, } @article {pmid33539025, year = {2021}, author = {Gostner, JM and Fuchs, D and Kurz, K}, title = {Metabolic Stress and Immunity: Nutrient-Sensing Kinases and Tryptophan Metabolism.}, journal = {Advances in experimental medicine and biology}, volume = {1275}, number = {}, pages = {395-405}, pmid = {33539025}, issn = {0065-2598}, mesh = {Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; Kynurenine ; Nutrients ; *Protein Serine-Threonine Kinases ; Stress, Physiological ; *Tryptophan ; }, abstract = {The tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO-1) has gained major attention due the immunoregulatory nature of this pathway. Both depletion of tryptophan concentrations as well as the accumulation of downstream metabolites are relevant for the mediation of the manifold consequences of increased tryptophan metabolism. Increased tryptophan catabolism is indicative for several chronic inflammatory disorders such as infections, autoimmune diseases or cancer. Low tryptophan availability is likely to be involved in the manifestation of a variety of comorbidities such as anemia, cachexia, depression and neurocognitive disturbances.Several nutrient sensing kinases are implicated in the downstream effects of dysregulated tryptophan metabolism. These include mechanisms that were conserved during evolution but have gained special features in multicellular eukaryotes, such as pathways regulated by eukaryotic translation initiation factor 2 (eIF-2)-alpha kinase (GCN2, also named general control nonderepressible 2 kinase), 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and target of rapamycin (TOR).The interplay between IDO-1 and above-mentioned pathway seems to be highly context dependent. A better understanding of the crosstalk is necessary to support the search for druggable targets for the treatment of inflammatory and autoimmune disorders.}, } @article {pmid33535472, year = {2021}, author = {Bonmati-Carrion, MA and Tomas-Loba, A}, title = {Melatonin and Cancer: A Polyhedral Network Where the Source Matters.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {33535472}, issn = {2076-3921}, support = {20401/SF/17//Fundación Séneca/ ; 19899/GERM/15//Fundación Séneca/ ; RYC2018-025622-I//Ministerio de Ciencia, Innovación y Universidades/ ; BFERO2020.01//Fundación Fero/ ; LeonardoFellowship//Fundación BBVA/ ; RTI2018-093528-B-I00//Ministerio de Ciencia, Innovación y Universidades/ ; CB16/10/00239//Ministerio de Economía y Competitividad/ ; }, abstract = {Melatonin is one of the most phylogenetically conserved signals in biology. Although its original function was probably related to its antioxidant capacity, this indoleamine has been "adopted" by multicellular organisms as the "darkness signal" when secreted in a circadian manner and is acutely suppressed by light at night by the pineal gland. However, melatonin is also produced by other tissues, which constitute its extrapineal sources. Apart from its undisputed chronobiotic function, melatonin exerts antioxidant, immunomodulatory, pro-apoptotic, antiproliferative, and anti-angiogenic effects, with all these properties making it a powerful antitumor agent. Indeed, this activity has been demonstrated to be mediated by interfering with various cancer hallmarks, and different epidemiological studies have also linked light at night (melatonin suppression) with a higher incidence of different types of cancer. In 2007, the World Health Organization classified night shift work as a probable carcinogen due to circadian disruption, where melatonin plays a central role. Our aim is to review, from a global perspective, the role of melatonin both from pineal and extrapineal origin, as well as their possible interplay, as an intrinsic factor in the incidence, development, and progression of cancer. Particular emphasis will be placed not only on those mechanisms related to melatonin's antioxidant nature but also on the recently described novel roles of melatonin in microbiota and epigenetic regulation.}, } @article {pmid33535413, year = {2021}, author = {Parker, GA}, title = {How Soon Hath Time… A History of Two "Seminal" Publications.}, journal = {Cells}, volume = {10}, number = {2}, pages = {}, pmid = {33535413}, issn = {2073-4409}, mesh = {Animals ; Female ; Insecta ; Male ; Sexual Selection/*physiology ; }, abstract = {This review documents the history of the two papers written half a century ago that relate to this special issue of Cells. The first, "Sperm competition and its evolutionary consequences in the insects" (Biological Reviews, 1970), stressed that sexual selection continues after ejaculation, resulting in many adaptations (e.g., postcopulatory guarding phases, copulatory plugs, seminal fluid components that modify female reproduction, and optimal ejaculation strategies), an aspect not considered by Darwin in his classic treatise of 1871. Sperm competition has subsequently been studied in many taxa, and post-copulatory sexual selection is now considered an important sequel to Darwinian pre-copulatory sexual selection. The second, "The origin and evolution of gamete dimorphism and the male-female phenomenon" (Journal of Theoretical Biology, 1972) showed how selection, based on gamete competition between individuals, can give rise to anisogamy in an isogamous broadcast spawning ancestor. This theory, which has subsequently been developed in various ways, is argued to form the most powerful explanation of why there are two sexes in most multicellular organisms. Together, the two papers have influenced our general understanding of the evolutionary differentiation of the two forms of gametic cells, and the divergence of sexual strategies between males and females under sexual selection.}, } @article {pmid33529558, year = {2021}, author = {Berger, D and Stångberg, J and Baur, J and Walters, RJ}, title = {Elevated temperature increases genome-wide selection on de novo mutations.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1944}, pages = {20203094}, pmid = {33529558}, issn = {1471-2954}, mesh = {*Adaptation, Physiological ; Animals ; *Climate Change ; Coleoptera/*genetics ; DNA Mutational Analysis ; Mutation ; *Selection, Genetic ; *Temperature ; }, abstract = {Adaptation in new environments depends on the amount of genetic variation available for evolution, and the efficacy by which natural selection discriminates among this variation. However, whether some ecological factors reveal more genetic variation, or impose stronger selection pressures than others, is typically not known. Here, we apply the enzyme kinetic theory to show that rising global temperatures are predicted to intensify natural selection throughout the genome by increasing the effects of DNA sequence variation on protein stability. We test this prediction by (i) estimating temperature-dependent fitness effects of induced mutations in seed beetles adapted to ancestral or elevated temperature, and (ii) calculate 100 paired selection estimates on mutations in benign versus stressful environments from unicellular and multicellular organisms. Environmental stress per se did not increase mean selection on de novo mutation, suggesting that the cost of adaptation does not generally increase in new ecological settings to which the organism is maladapted. However, elevated temperature increased the mean strength of selection on genome-wide polymorphism, signified by increases in both mutation load and mutational variance in fitness. These results have important implications for genetic diversity gradients and the rate and repeatability of evolution under climate change.}, } @article {pmid33520185, year = {2021}, author = {Naimark, E and Kirpotin, D and Boeva, N and Gmoshinskiy, V and Kalinina, M and Lyupina, Y and Markov, A and Nikitin, M and Shokurov, A and Volkov, D}, title = {Taphonomic experiments imply a possible link between the evolution of multicellularity and the fossilization potential of soft-bodied organisms.}, journal = {Ecology and evolution}, volume = {11}, number = {2}, pages = {1037-1056}, pmid = {33520185}, issn = {2045-7758}, abstract = {The reliability of evolutionary reconstructions based on the fossil record critically depends on our knowledge of the factors affecting the fossilization of soft-bodied organisms. Despite considerable research effort, these factors are still poorly understood. In order to elucidate the main prerequisites for the preservation of soft-bodied organisms, we conducted long-term (1-5 years) taphonomic experiments with the model crustacean Artemia salina buried in five different sediments. The subsequent analysis of the carcasses and sediments revealed that, in our experimental settings, better preservation was associated with the fast deposition of aluminum and silicon on organic tissues. Other elements such as calcium, magnesium, and iron, which can also accumulate quickly on the carcasses, appear to be much less efficient in preventing decay. Next, we asked if the carcasses of uni- and multicellular organisms differ in their ability to accumulate aluminum ions on their surface. The experiments with the flagellate Euglena gracilis and the sponge Spongilla lacustris showed that aluminum ions are more readily deposited onto a multicellular body. This was further confirmed by the experiments with uni- and multicellular stages of the social ameba Dictyostelium discoideum. The results lead us to speculate that the evolution of cell adhesion molecules, which provide efficient cell-cell and cell-substrate binding, probably can explain the rich fossil record of soft-bodied animals, the comparatively poor fossil record of nonskeletal unicellular eukaryotes, and the explosive emergence of the Cambrian diversity of soft-bodied fossils.}, } @article {pmid33507545, year = {2021}, author = {Li, J and Meng, Q and Fu, Y and Yu, X and Ji, T and Chao, Y and Chen, Q and Li, Y and Bian, H}, title = {Novel insights: Dynamic foam cells derived from the macrophage in atherosclerosis.}, journal = {Journal of cellular physiology}, volume = {236}, number = {9}, pages = {6154-6167}, doi = {10.1002/jcp.30300}, pmid = {33507545}, issn = {1097-4652}, mesh = {Animals ; Atherosclerosis/*pathology ; Cell Communication ; Cholesterol/metabolism ; Esterification ; Foam Cells/metabolism/*pathology ; Humans ; Metabolome ; }, abstract = {Atherosclerosis can be regarded as a chronic disease derived from the interaction between disordered lipoproteins and an unsuitable immune response. The evolution of foam cells is not only a significant pathological change in the early stage of atherosclerosis but also a key stage in the occurrence and development of atherosclerosis. The formation of foam cells is mainly caused by the imbalance among lipids uptake, lipids treatment, and reverse cholesterol transport. Although a large number of studies have summarized the source of foam cells and the mechanism of foam cells formation, we propose a new idea about foam cells in atherosclerosis. Rather than an isolated microenvironment, the macrophage multiple lipid uptake pathways, lipid internalization, lysosome, mitochondria, endoplasmic reticulum, neutral cholesterol ester hydrolase (NCEH), acyl-coenzyme A-cholesterol acyltransferase (ACAT), and reverse cholesterol transport are mutually influential, and form a dynamic process under multi-factor regulation. The macrophage takes on different uptake lipid statuses depending on multiple uptake pathways and intracellular lipids, lipid metabolites versus pro-inflammatory factors. Except for NCEH and ACAT, the lipid internalization of macrophages also depends on multicellular organelles including the lysosome, mitochondria, and endoplasmic reticulum, which are associated with each other. A dynamic balance between esterification and hydrolysis of cholesterol for macrophages is essential for physiology and pathology. Therefore, we propose that the foam cell in the process of atherosclerosis may be dynamic under multi-factor regulation, and collate this study to provide a holistic and dynamic idea of the foam cell.}, } @article {pmid33487114, year = {2021}, author = {Dinet, C and Michelot, A and Herrou, J and Mignot, T}, title = {Linking single-cell decisions to collective behaviours in social bacteria.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1820}, pages = {20190755}, pmid = {33487114}, issn = {1471-2970}, mesh = {Microbial Interactions/*physiology ; Myxococcus xanthus/*physiology ; }, abstract = {Social bacteria display complex behaviours whereby thousands of cells collectively and dramatically change their form and function in response to nutrient availability and changing environmental conditions. In this review, we focus on Myxococcus xanthus motility, which supports spectacular transitions based on prey availability across its life cycle. A large body of work suggests that these behaviours require sensory capacity implemented at the single-cell level. Focusing on recent genetic work on a core cellular pathway required for single-cell directional decisions, we argue that signal integration, multi-modal sensing and memory are at the root of decision making leading to multicellular behaviours. Hence, Myxococcus may be a powerful biological system to elucidate how cellular building blocks cooperate to form sensory multicellular assemblages, a possible origin of cognitive mechanisms in biological systems. This article is part of the theme issue 'Basal cognition: conceptual tools and the view from the single cell'.}, } @article {pmid33487113, year = {2021}, author = {Schaap, P}, title = {From environmental sensing to developmental control: cognitive evolution in dictyostelid social amoebas.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1820}, pages = {20190756}, pmid = {33487113}, issn = {1471-2970}, mesh = {*Biological Evolution ; *Cognition ; Dictyosteliida/*physiology ; *Quorum Sensing ; *Signal Transduction ; }, abstract = {Dictyostelid social amoebas respond to starvation by self-organizing into multicellular slugs that migrate towards light to construct spore-bearing structures. These behaviours depend on excitable networks that enable amoebas to produce propagating waves of the chemoattractant cAMP, and to respond by directional movement. cAMP additionally regulates cell differentiation throughout development, with differentiation and cell movement being coordinated by interaction of the stalk inducer c-di-GMP with the adenylate cyclase that generates cAMP oscillations. Evolutionary studies indicate how the manifold roles of cAMP in multicellular development evolved from a role as intermediate for starvation-induced encystation in the unicellular ancestor. A merger of this stress response with the chemotaxis excitable networks yielded the developmental complexity and cognitive capabilities of extant Dictyostelia. This article is part of the theme issue 'Basal cognition: conceptual tools and the view from the single cell'.}, } @article {pmid33479850, year = {2021}, author = {Tourigny, DS}, title = {Cooperative metabolic resource allocation in spatially-structured systems.}, journal = {Journal of mathematical biology}, volume = {82}, number = {1-2}, pages = {5}, pmid = {33479850}, issn = {1432-1416}, mesh = {Biological Evolution ; Entropy ; Humans ; Models, Biological ; Quorum Sensing ; Resource Allocation ; *Selection, Genetic ; *Social Behavior ; }, abstract = {Natural selection has shaped the evolution of cells and multi-cellular organisms such that social cooperation can often be preferred over an individualistic approach to metabolic regulation. This paper extends a framework for dynamic metabolic resource allocation based on the maximum entropy principle to spatiotemporal models of metabolism with cooperation. Much like the maximum entropy principle encapsulates 'bet-hedging' behaviour displayed by organisms dealing with future uncertainty in a fluctuating environment, its cooperative extension describes how individuals adapt their metabolic resource allocation strategy to further accommodate limited knowledge about the welfare of others within a community. The resulting theory explains why local regulation of metabolic cross-feeding can fulfil a community-wide metabolic objective if individuals take into consideration an ensemble measure of total population performance as the only form of global information. The latter is likely supplied by quorum sensing in microbial systems or signalling molecules such as hormones in multi-cellular eukaryotic organisms.}, } @article {pmid33479022, year = {2021}, author = {Kjellin, J and Avesson, L and Reimegård, J and Liao, Z and Eichinger, L and Noegel, A and Glöckner, G and Schaap, P and Söderbom, F}, title = {Abundantly expressed class of noncoding RNAs conserved through the multicellular evolution of dictyostelid social amoebas.}, journal = {Genome research}, volume = {31}, number = {3}, pages = {436-447}, pmid = {33479022}, issn = {1549-5469}, support = {BB/D013453/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/G020426/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Dictyostelium/classification/*cytology/*genetics ; *Evolution, Molecular ; *Phylogeny ; RNA, Untranslated/*genetics ; }, abstract = {Aggregative multicellularity has evolved multiple times in diverse groups of eukaryotes, exemplified by the well-studied development of dictyostelid social amoebas, for example, Dictyostelium discoideum However, it is still poorly understood why multicellularity emerged in these amoebas while the majority of other members of Amoebozoa are unicellular. Previously, a novel type of noncoding RNA, Class I RNAs, was identified in D. discoideum and shown to be important for normal multicellular development. Here, we investigated Class I RNA evolution and its connection to multicellular development. We identified a large number of new Class I RNA genes by constructing a covariance model combined with a scoring system based on conserved upstream sequences. Multiple genes were predicted in representatives of each major group of Dictyostelia and expression analysis confirmed that our search approach identifies expressed Class I RNA genes with high accuracy and sensitivity and that the RNAs are developmentally regulated. Further studies showed that Class I RNAs are ubiquitous in Dictyostelia and share highly conserved structure and sequence motifs. In addition, Class I RNA genes appear to be unique to dictyostelid social amoebas because they could not be identified in outgroup genomes, including their closest known relatives. Our results show that Class I RNA is an ancient class of ncRNAs, likely to have been present in the last common ancestor of Dictyostelia dating back at least 600 million years. Based on previous functional analyses and the presented evolutionary investigation, we hypothesize that Class I RNAs were involved in evolution of multicellularity in Dictyostelia.}, } @article {pmid33471791, year = {2021}, author = {Miele, L and De Monte, S}, title = {Aggregative cycles evolve as a solution to conflicts in social investment.}, journal = {PLoS computational biology}, volume = {17}, number = {1}, pages = {e1008617}, pmid = {33471791}, issn = {1553-7358}, mesh = {*Biological Evolution ; Cell Aggregation/*physiology ; Cell Movement/*physiology ; Computational Biology ; Dictyostelium/cytology/physiology ; *Models, Biological ; }, abstract = {Multicellular organization is particularly vulnerable to conflicts between different cell types when the body forms from initially isolated cells, as in aggregative multicellular microbes. Like other functions of the multicellular phase, coordinated collective movement can be undermined by conflicts between cells that spend energy in fuelling motion and 'cheaters' that get carried along. The evolutionary stability of collective behaviours against such conflicts is typically addressed in populations that undergo extrinsically imposed phases of aggregation and dispersal. Here, via a shift in perspective, we propose that aggregative multicellular cycles may have emerged as a way to temporally compartmentalize social conflicts. Through an eco-evolutionary mathematical model that accounts for individual and collective strategies of resource acquisition, we address regimes where different motility types coexist. Particularly interesting is the oscillatory regime that, similarly to life cycles of aggregative multicellular organisms, alternates on the timescale of several cell generations phases of prevalent solitary living and starvation-triggered aggregation. Crucially, such self-organized oscillations emerge as a result of evolution of cell traits associated to conflict escalation within multicellular aggregates.}, } @article {pmid33468253, year = {2021}, author = {Xu, L and Zhang, M and Shi, L and Yang, X and Chen, L and Cao, N and Lei, A and Cao, Y}, title = {Neural stemness contributes to cell tumorigenicity.}, journal = {Cell & bioscience}, volume = {11}, number = {1}, pages = {21}, pmid = {33468253}, issn = {2045-3701}, support = {31671499//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Previous studies demonstrated the dependence of cancer on nerve. Recently, a growing number of studies reveal that cancer cells share the property and regulatory network with neural stem/progenitor cells. However, relationship between the property of neural stemness and cell tumorigenicity is unknown.

RESULTS: We show that neural stem/progenitor cells, but not non-neural embryonic or somatic stem/progenitor cell types, exhibit tumorigenicity and the potential for differentiation into tissue types of all germ layers when they are placed in non-native environment by transplantation into immunodeficient nude mice. Likewise, cancer cells capable of tumor initiation have the property of neural stemness because of their abilities in neurosphere formation in neural stem cell-specific serum-free medium and in differentiation potential, in addition to their neuronal differentiation potential that was characterized previously. Moreover, loss of a pro-differentiation factor in myoblasts, which have no tumorigenicity, lead to the loss of myoblast identity, and gain of the property of neural stemness, tumorigenicity and potential for re-differentiation. By contrast, loss of neural stemness via differentiation results in the loss of tumorigenicity. These suggest that the property of neural stemness contributes to cell tumorigenicity, and tumor phenotypic heterogeneity might be an effect of differentiation potential of neural stemness. Bioinformatic analysis reveals that neural genes in general are correlated with embryonic development and cancer, in addition to their role in neural development; whereas non-neural genes are not. Most of neural specific genes emerged in typical species representing transition from unicellularity to multicellularity during evolution. Genes in Monosiga brevicollis, a unicellular species that is a closest known relative of metazoans, are biased toward neural cells.

CONCLUSIONS: We suggest that the property of neural stemness is the source of cell tumorigenicity. This is due to that neural biased unicellular state is the ground state for multicellularity and hence cell type diversification or differentiation during evolution, and tumorigenesis is a process of restoration of neural ground state in somatic cells along a default route that is pre-determined by an evolutionary advantage of neural state.}, } @article {pmid33460641, year = {2021}, author = {Schrankel, CS and Hamdoun, A}, title = {Early patterning of ABCB, ABCC, and ABCG transporters establishes unique territories of small molecule transport in embryonic mesoderm and endoderm.}, journal = {Developmental biology}, volume = {472}, number = {}, pages = {115-124}, pmid = {33460641}, issn = {1095-564X}, support = {F32 ES029843/ES/NIEHS NIH HHS/United States ; R01 ES027921/ES/NIEHS NIH HHS/United States ; R01 ES030318/ES/NIEHS NIH HHS/United States ; }, mesh = {ATP-Binding Cassette Transporters/genetics/*metabolism ; Animals ; Biological Transport ; Endoderm/*metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; In Situ Hybridization ; Intestinal Mucosa/metabolism ; Intestines/embryology ; Mesoderm/*metabolism ; Sea Urchins/*embryology/genetics/metabolism ; Signal Transduction ; }, abstract = {Directed intercellular movement of diverse small molecules, including metabolites, signal molecules and xenobiotics, is a key feature of multicellularity. Networks of small molecule transporters (SMTs), including several ATP Binding Cassette (ABC) transporters, are central to this process. While small molecule transporters are well described in differentiated organs, little is known about their patterns of expression in early embryogenesis. Here we report the pattern of ABC-type SMT expression and activity during the early development of sea urchins. Of the six major ABCs in this embryo (ABCB1, -B4, -C1, -C4, -C5 and -G2), three expression patterns were observed: 1) ABCB1 and ABCC1 are first expressed ubiquitously, and then become enriched in endoderm and ectoderm-derived structures. 2) ABCC4 and ABCC5 are restricted to a ring of mesoderm in the blastula and ABCC4 is later expressed in the coelomic pouches, the embryonic niche of the primordial germ cells. 3) ABCB4 and ABCG2 are expressed exclusively in endoderm-fated cells. Assays with fluorescent substrates and inhibitors of transporters revealed a ring of ABCC4 efflux activity emanating from ABCC4[+] mesodermal cells. Similarly, ABCB1 and ABCB4 efflux activity was observed in the developing gut, prior to the onset of feeding. This study reveals the early establishment of unique territories of small molecule transport during embryogenesis. A pattern of ABCC4/C5 expression is consistent with signaling functions during gut invagination and germ line development, while a later pattern of ABCB1/B4 and ABCG2 is consistent with roles in the embryonic gut. This work provides a conceptual framework with which to examine the function and evolution of SMT networks and to define the specific developmental pathways that drive the expression of these genes.}, } @article {pmid33455859, year = {2021}, author = {Jana, SC}, title = {Centrosome structure and biogenesis: Variations on a theme?.}, journal = {Seminars in cell & developmental biology}, volume = {110}, number = {}, pages = {123-138}, doi = {10.1016/j.semcdb.2020.10.014}, pmid = {33455859}, issn = {1096-3634}, mesh = {Actins/genetics/metabolism ; Animals ; Biodiversity ; Biological Evolution ; Cell Cycle/genetics ; Centrioles/metabolism/*ultrastructure ; Chlorophyta/genetics/metabolism/ultrastructure ; Cilia/metabolism/*ultrastructure ; Eukaryotic Cells/metabolism/ultrastructure ; Gene Expression Regulation ; Humans ; Microtubule-Associated Proteins/classification/*genetics/metabolism ; Microtubules/metabolism/*ultrastructure ; *Organelle Biogenesis ; Species Specificity ; Tubulin/genetics/metabolism ; }, abstract = {Centrosomes are composed of two orthogonally arranged centrioles surrounded by an electron-dense matrix called the pericentriolar material (PCM). Centrioles are cylinders with diameters of ~250 nm, are several hundred nanometres in length and consist of 9-fold symmetrically arranged microtubules (MT). In dividing animal cells, centrosomes act as the principal MT-organising centres and they also organise actin, which tunes cytoplasmic MT nucleation. In some specialised cells, the centrosome acquires additional critical structures and converts into the base of a cilium with diverse functions including signalling and motility. These structures are found in most eukaryotes and are essential for development and homoeostasis at both cellular and organism levels. The ultrastructure of centrosomes and their derived organelles have been known for more than half a century. However, recent advances in a number of techniques have revealed the high-resolution structures (at Å-to-nm scale resolution) of centrioles and have begun to uncover the molecular principles underlying their properties, including: protein components; structural elements; and biogenesis in various model organisms. This review covers advances in our understanding of the features and processes that are critical for the biogenesis of the evolutionarily conserved structures of the centrosomes. Furthermore, it discusses how variations of these aspects can generate diversity in centrosome structure and function among different species and even between cell types within a multicellular organism.}, } @article {pmid33449631, year = {2021}, author = {Duran-Nebreda, S and Pla, J and Vidiella, B and Piñero, J and Conde-Pueyo, N and Solé, R}, title = {Synthetic Lateral Inhibition in Periodic Pattern Forming Microbial Colonies.}, journal = {ACS synthetic biology}, volume = {10}, number = {2}, pages = {277-285}, pmid = {33449631}, issn = {2161-5063}, mesh = {Developmental Biology/methods ; Escherichia coli/*genetics/*growth & development ; *Gene Regulatory Networks ; *Genes, Synthetic ; Genetic Engineering/*methods ; Plasmids/genetics ; Synthetic Biology/methods ; }, abstract = {Multicellular entities are characterized by intricate spatial patterns, intimately related to the functions they perform. These patterns are often created from isotropic embryonic structures, without external information cues guiding the symmetry breaking process. Mature biological structures also display characteristic scales with repeating distributions of signals or chemical species across space. Many candidate patterning modules have been used to explain processes during development and typically include a set of interacting and diffusing chemicals or agents known as morphogens. Great effort has been put forward to better understand the conditions in which pattern-forming processes can occur in the biological domain. However, evidence and practical knowledge allowing us to engineer symmetry-breaking is still lacking. Here we follow a different approach by designing a synthetic gene circuit in E. coli that implements a local activation long-range inhibition mechanism. The synthetic gene network implements an artificial differentiation process that changes the physicochemical properties of the agents. Using both experimental results and modeling, we show that the proposed system is capable of symmetry-breaking leading to regular spatial patterns during colony growth. Studying how these patterns emerge is fundamental to further our understanding of the evolution of biocomplexity and the role played by self-organization. The artificial system studied here and the engineering perspective on embryogenic processes can help validate developmental theories and identify universal properties underpinning biological pattern formation, with special interest for the area of synthetic developmental biology.}, } @article {pmid33449147, year = {2021}, author = {Kruger, AN and Mueller, JL}, title = {Mechanisms of meiotic drive in symmetric and asymmetric meiosis.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {78}, number = {7}, pages = {3205-3218}, pmid = {33449147}, issn = {1420-9071}, support = {HD094736//National Institute of Child Health and Human Development/ ; R01 HD094736/HD/NICHD NIH HHS/United States ; 1256260//National Science Foundation/ ; T32 GM007544/GM/NIGMS NIH HHS/United States ; T32GM007544/GM/NIGMS NIH HHS/United States ; T32GM007544/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Chromosome Segregation ; Humans ; *Meiosis ; Spindle Apparatus/*physiology ; }, abstract = {Meiotic drive, the non-Mendelian transmission of chromosomes to the next generation, functions in asymmetric or symmetric meiosis across unicellular and multicellular organisms. In asymmetric meiosis, meiotic drivers act to alter a chromosome's spatial position in a single egg. In symmetric meiosis, meiotic drivers cause phenotypic differences between gametes with and without the driver. Here we discuss existing models of meiotic drive, highlighting the underlying mechanisms and regulation governing systems for which the most is known. We focus on outstanding questions surrounding these examples and speculate on how new meiotic drive systems evolve and how to detect them.}, } @article {pmid33446527, year = {2021}, author = {Stadler, T and Pybus, OG and Stumpf, MPH}, title = {Phylodynamics for cell biologists.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6526}, pages = {}, doi = {10.1126/science.aah6266}, pmid = {33446527}, issn = {1095-9203}, mesh = {Animals ; Caenorhabditis elegans/cytology/growth & development ; Cell Biology/trends ; *Cell Lineage ; Humans ; *Phylogeny ; *Single-Cell Analysis ; Stem Cells/cytology/physiology ; }, abstract = {Multicellular organisms are composed of cells connected by ancestry and descent from progenitor cells. The dynamics of cell birth, death, and inheritance within an organism give rise to the fundamental processes of development, differentiation, and cancer. Technical advances in molecular biology now allow us to study cellular composition, ancestry, and evolution at the resolution of individual cells within an organism or tissue. Here, we take a phylogenetic and phylodynamic approach to single-cell biology. We explain how "tree thinking" is important to the interpretation of the growing body of cell-level data and how ecological null models can benefit statistical hypothesis testing. Experimental progress in cell biology should be accompanied by theoretical developments if we are to exploit fully the dynamical information in single-cell data.}, } @article {pmid33440882, year = {2021}, author = {Takahashi, T}, title = {Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function.}, journal = {International journal of molecular sciences}, volume = {22}, number = {2}, pages = {}, pmid = {33440882}, issn = {1422-0067}, support = {JP17K07495 and JP20K06751//Japan Society for the Promotion of Science/ ; }, mesh = {Acetylcholine/*metabolism ; Age Factors ; Animals ; Biomarkers ; Brain/cytology/metabolism ; Cell Differentiation/genetics ; Homeostasis ; Humans ; Organ Specificity ; Receptors, Cholinergic/*metabolism ; *Signal Transduction ; Stem Cells/cytology/*metabolism ; }, abstract = {Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.}, } @article {pmid33440837, year = {2021}, author = {Bredon, M and Depuydt, E and Brisson, L and Moulin, L and Charles, C and Haenn, S and Moumen, B and Bouchon, D}, title = {Effects of Dysbiosis and Dietary Manipulation on the Digestive Microbiota of a Detritivorous Arthropod.}, journal = {Microorganisms}, volume = {9}, number = {1}, pages = {}, pmid = {33440837}, issn = {2076-2607}, support = {BiodivUP//State-Region Planning Contracts (CPER), European Regional Development Fund (FEDER)/ ; }, abstract = {The crucial role of microbes in the evolution, development, health, and ecological interactions of multicellular organisms is now widely recognized in the holobiont concept. However, the structure and stability of microbiota are highly dependent on abiotic and biotic factors, especially in the gut, which can be colonized by transient bacteria depending on the host's diet. We studied these impacts by manipulating the digestive microbiota of the detritivore Armadillidium vulgare and analyzing the consequences on its structure and function. Hosts were exposed to initial starvation and then were fed diets that varied the different components of lignocellulose. A total of 72 digestive microbiota were analyzed according to the type of the diet (standard or enriched in cellulose, lignin, or hemicellulose) and the period following dysbiosis. The results showed that microbiota from the hepatopancreas were very stable and resilient, while the most diverse and labile over time were found in the hindgut. Dysbiosis and selective diets may have affected the host fitness by altering the structure of the microbiota and its predicted functions. Overall, these modifications can therefore have effects not only on the holobiont, but also on the "eco-holobiont" conceptualization of macroorganisms.}, } @article {pmid33436625, year = {2021}, author = {Chaikeeratisak, V and Birkholz, EA and Prichard, AM and Egan, ME and Mylvara, A and Nonejuie, P and Nguyen, KT and Sugie, J and Meyer, JR and Pogliano, J}, title = {Viral speciation through subcellular genetic isolation and virogenesis incompatibility.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {342}, pmid = {33436625}, issn = {2041-1723}, support = {R01 GM104556/GM/NIGMS NIH HHS/United States ; R01 GM129245/GM/NIGMS NIH HHS/United States ; T32 GM007240/GM/NIGMS NIH HHS/United States ; T32 GM133351/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteriophages/*genetics ; Cell Nucleus/metabolism ; *Genetic Speciation ; Green Fluorescent Proteins/metabolism ; Pseudomonas aeruginosa/virology ; Species Specificity ; Subcellular Fractions ; }, abstract = {Understanding how biological species arise is critical for understanding the evolution of life on Earth. Bioinformatic analyses have recently revealed that viruses, like multicellular life, form reproductively isolated biological species. Viruses are known to share high rates of genetic exchange, so how do they evolve genetic isolation? Here, we evaluate two related bacteriophages and describe three factors that limit genetic exchange between them: 1) A nucleus-like compartment that physically separates replicating phage genomes, thereby limiting inter-phage recombination during co-infection; 2) A tubulin-based spindle that orchestrates phage replication and forms nonfunctional hybrid polymers; and 3) A nuclear incompatibility factor that reduces phage fitness. Together, these traits maintain species differences through Subcellular Genetic Isolation where viral genomes are physically separated during co-infection, and Virogenesis Incompatibility in which the interaction of cross-species components interferes with viral production.}, } @article {pmid33421998, year = {2021}, author = {Mondal, M and Peter, J and Scarbrough, O and Flynt, A}, title = {Environmental RNAi pathways in the two-spotted spider mite.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {42}, pmid = {33421998}, issn = {1471-2164}, support = {P20 GM103476/GM/NIGMS NIH HHS/United States ; 1616725//Directorate for Biological Sciences/ ; P204M103476//Mississippi IDeA Network of Biomedical Research Excellence (US)/ ; }, mesh = {Animals ; Gene Expression ; Plants ; RNA Interference ; *Tetranychidae/genetics ; }, abstract = {BACKGROUND: RNA interference (RNAi) regulates gene expression in most multicellular organisms through binding of small RNA effectors to target transcripts. Exploiting this process is a popular strategy for genetic manipulation and has applications that includes arthropod pest control. RNAi technologies are dependent on delivery method with the most convenient likely being feeding, which is effective in some animals while others are insensitive. The two-spotted spider mite, Tetranychus urticae, is prime candidate for developing RNAi approaches due to frequent occurrence of conventional pesticide resistance. Using a sequencing-based approach, the fate of ingested RNAs was explored to identify features and conditions that affect small RNA biogenesis from external sources to better inform RNAi design.

RESULTS: Biochemical and sequencing approaches in conjunction with extensive computational assessment were used to evaluate metabolism of ingested RNAs in T. urticae. This chelicerae arthropod shows only modest response to oral RNAi and has biogenesis pathways distinct from model organisms. Processing of synthetic and plant host RNAs ingested during feeding were evaluated to identify active substrates for spider mite RNAi pathways. Through cataloging characteristics of biochemically purified RNA from these sources, trans-acting small RNAs could be distinguished from degradation fragments and their origins documented.

CONCLUSIONS: Using a strategy that delineates small RNA processing, we found many transcripts have the potential to enter spider mite RNAi pathways, however, trans-acting RNAs appear very unstable and rare. This suggests potential RNAi pathway substrates from ingested materials are mostly degraded and infrequently converted into regulators of gene expression. Spider mites infest a variety of plants, and it would be maladaptive to generate diverse gene regulators from dietary RNAs. This study provides a framework for assessing RNAi technology in organisms where genetic and biochemical tools are absent and benefit rationale design of RNAi triggers for T.urticae.}, } @article {pmid33418487, year = {2021}, author = {Sagova-Mareckova, M and Boenigk, J and Bouchez, A and Cermakova, K and Chonova, T and Cordier, T and Eisendle, U and Elersek, T and Fazi, S and Fleituch, T and Frühe, L and Gajdosova, M and Graupner, N and Haegerbaeumer, A and Kelly, AM and Kopecky, J and Leese, F and Nõges, P and Orlic, S and Panksep, K and Pawlowski, J and Petrusek, A and Piggott, JJ and Rusch, JC and Salis, R and Schenk, J and Simek, K and Stovicek, A and Strand, DA and Vasquez, MI and Vrålstad, T and Zlatkovic, S and Zupancic, M and Stoeck, T}, title = {Expanding ecological assessment by integrating microorganisms into routine freshwater biomonitoring.}, journal = {Water research}, volume = {191}, number = {}, pages = {116767}, doi = {10.1016/j.watres.2020.116767}, pmid = {33418487}, issn = {1879-2448}, mesh = {Archaea/genetics ; *Biological Monitoring ; *Ecosystem ; Environmental Biomarkers ; Environmental Monitoring ; Fresh Water ; }, abstract = {Bioindication has become an indispensable part of water quality monitoring in most countries of the world, with the presence and abundance of bioindicator taxa, mostly multicellular eukaryotes, used for biotic indices. In contrast, microbes (bacteria, archaea and protists) are seldom used as bioindicators in routine assessments, although they have been recognized for their importance in environmental processes. Recently, the use of molecular methods has revealed unexpected diversity within known functional groups and novel metabolic pathways that are particularly important in energy and nutrient cycling. In various habitats, microbial communities respond to eutrophication, metals, and natural or anthropogenic organic pollutants through changes in diversity and function. In this review, we evaluated the common trends in these changes, documenting that they have value as bioindicators and can be used not only for monitoring but also for improving our understanding of the major processes in lotic and lentic environments. Current knowledge provides a solid foundation for exploiting microbial taxa, community structures and diversity, as well as functional genes, in novel monitoring programs. These microbial community measures can also be combined into biotic indices, improving the resolution of individual bioindicators. Here, we assess particular molecular approaches complemented by advanced bioinformatic analysis, as these are the most promising with respect to detailed bioindication value. We conclude that microbial community dynamics are a missing link important for our understanding of rapid changes in the structure and function of aquatic ecosystems, and should be addressed in the future environmental monitoring of freshwater ecosystems.}, } @article {pmid33412387, year = {2021}, author = {Liu, Q and Piao, H and Wang, Y and Zheng, D and Wang, W}, title = {Circulating exosomes in cardiovascular disease: Novel carriers of biological information.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {135}, number = {}, pages = {111148}, doi = {10.1016/j.biopha.2020.111148}, pmid = {33412387}, issn = {1950-6007}, mesh = {Animals ; Biomarkers/metabolism ; Cardiovascular Diseases/blood/genetics/*metabolism/therapy ; Cardiovascular System/*metabolism ; *Cell Communication ; Drug Carriers ; Exosomes/genetics/*metabolism/transplantation ; Gene Transfer Techniques ; Genetic Therapy ; Humans ; Signal Transduction ; }, abstract = {Exosomes are a group of nanosized extracellular vesicles that include various bioactive nucleic acids, lipids, and proteins. They originate from membrane invagination and are released by exocytosis, which can transmit signals to target cells to achieve cell-to-cell communication and maintain homeostasis. The heart is a complex multicellular organ that contains resident cell types such as fibroblasts, endothelial cells, and smooth muscle cells. Communication between different cell types and immune systems is essential for the dynamic equilibrium of the cardiac internal environment. Intercellular communication is a universal phenomenon mediated by exosomes and their contents during several pathological processes in cardiovascular diseases, such as cardiomyocyte hypertrophy, apoptosis, and angiogenesis. Therefore, exosomes can be used as novel invasive diagnostic biomarkers in multiple diseases, including atherosclerosis, myocardial ischemia, cardiac fibrosis, and ischemia-reperfusion injury. In addition, the biocompatible nature and low immunogenicity of exosomes make them high-quality nanoparticle drug carriers with potential applications in translational medicine and therapeutic strategies. Here, we focus on the biogenesis, isolation, biological functions, and future application prospects of exosomes in cardiovascular disease.}, } @article {pmid33411582, year = {2021}, author = {Costa, M and Blaschke, TF and Amara, SG and Meyer, UA and Insel, PA}, title = {Introduction to the Theme "Old and New Toxicology: Interfaces with Pharmacology".}, journal = {Annual review of pharmacology and toxicology}, volume = {61}, number = {}, pages = {1-7}, doi = {10.1146/annurev-pharmtox-092220-033032}, pmid = {33411582}, issn = {1545-4304}, mesh = {Female ; Humans ; Male ; *Pharmacology ; *Toxicology ; }, abstract = {The theme of Volume 61 is "Old and New Toxicology: Interfaces with Pharmacology." Old toxicology is exemplified by the authors of the autobiographical articles: B.M. Olivera's work on toxins and venoms from cone snails and P. Taylor's studies of acetylcholinesterase and the nicotinic cholinergic receptor, which serve as sites of action for numerous pesticides and venoms. Other articles in this volume focus on new understanding and new types of toxicology, including (a) arsenic toxicity, which is an ancient poison that, through evolution, has caused most multicellular organisms to express an active arsenic methyltransferase to methylate arsenite, which accelerates the excretion of arsenic from the body; (b) small molecules that react with lipid dicarbonyls, which are now considered the most toxic oxidative stress end products; (c) immune checkpoint inhibitors (ICIs), which have revolutionized cancer therapy but have numerous immune-related adverse events, including cardiovascular complications; (d) autoimmunity caused by the environment; (e) idiosyncratic drug-induced liver disease, which together with the toxicity of ICIs represents new toxicology interfacing with pharmacology; and (f) sex differences in the development of cardiovascular disease, with men more susceptible than women to vascular inflammation that initiates and perpetuates disease. These articles and others in Volume 61 reflect the interface and close integration of pharmacology and toxicology that began long ago but continues today.}, } @article {pmid33397407, year = {2021}, author = {Bourdareau, S and Tirichine, L and Lombard, B and Loew, D and Scornet, D and Wu, Y and Coelho, SM and Cock, JM}, title = {Histone modifications during the life cycle of the brown alga Ectocarpus.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {12}, pmid = {33397407}, issn = {1474-760X}, mesh = {Chromatin/metabolism ; Epigenesis, Genetic ; Genome ; Germ Cells, Plant ; *Histone Code ; *Histones ; *Life Cycle Stages ; Phaeophyta/*genetics/physiology ; Phylogeny ; Plants/genetics ; *Protein Processing, Post-Translational ; }, abstract = {BACKGROUND: Brown algae evolved complex multicellularity independently of the animal and land plant lineages and are the third most developmentally complex phylogenetic group on the planet. An understanding of developmental processes in this group is expected to provide important insights into the evolutionary events necessary for the emergence of complex multicellularity. Here, we focus on mechanisms of epigenetic regulation involving post-translational modifications of histone proteins.

RESULTS: A total of 47 histone post-translational modifications are identified, including a novel mark H2AZR38me1, but Ectocarpus lacks both H3K27me3 and the major polycomb complexes. ChIP-seq identifies modifications associated with transcription start sites and gene bodies of active genes and with transposons. H3K79me2 exhibits an unusual pattern, often marking large genomic regions spanning several genes. Transcription start sites of closely spaced, divergently transcribed gene pairs share a common nucleosome-depleted region and exhibit shared histone modification peaks. Overall, patterns of histone modifications are stable through the life cycle. Analysis of histone modifications at generation-biased genes identifies a correlation between the presence of specific chromatin marks and the level of gene expression.

CONCLUSIONS: The overview of histone post-translational modifications in the brown alga presented here will provide a foundation for future studies aimed at understanding the role of chromatin modifications in the regulation of brown algal genomes.}, } @article {pmid33389562, year = {2021}, author = {Furumizu, C and Sawa, S}, title = {Insight into early diversification of leucine-rich repeat receptor-like kinases provided by the sequenced moss and hornwort genomes.}, journal = {Plant molecular biology}, volume = {107}, number = {4-5}, pages = {337-353}, pmid = {33389562}, issn = {1573-5028}, support = {17H03967//Japan Society for the Promotion of Science/ ; 18H04841//Japan Society for the Promotion of Science/ ; 18H04625//Japan Society for the Promotion of Science/ ; 18H05487//Japan Society for the Promotion of Science/ ; 20H00422//Japan Society for the Promotion of Science/ ; 20K06770//Japan Society for the Promotion of Science/ ; }, mesh = {Amino Acid Sequence ; Anthocerotophyta/*genetics ; Computer Simulation ; Evolution, Molecular ; *Genetic Variation ; Genome, Plant/*genetics ; Genomics/methods ; Phylogeny ; Plant Proteins/chemistry/classification/*genetics ; Protein Domains ; Protein Kinases/chemistry/classification/*genetics ; Sequence Homology, Amino Acid ; Signal Transduction/genetics ; Sphagnopsida/*genetics ; }, abstract = {Identification of the subfamily X leucine-rich repeat receptor-like kinases in the recently sequenced moss and hornwort genomes points to their diversification into distinct groups during early evolution of land plants. Signal transduction mediated through receptor-ligand interactions plays key roles in controlling developmental and physiological processes of multicellular organisms, and plants employ diverse receptors in signaling. Leucine-rich repeat receptor-like kinases (LRR-RLKs) represent one of the largest receptor classes in plants and are structurally classified into subfamilies. LRR-RLKs of the subfamily X are unique in the variety of their signaling roles; they include receptors for steroid or peptide hormones as well as negative regulators of signaling through binding to other LRR-RLKs, raising a question as to how they diversified. However, our understanding of diversification processes of LRR-RLKs has been hindered by the paucity of genomic data in non-seed plants and limited taxa sampling in previous phylogenetic analyses. Here we analyzed the phylogeny of LRR-RLK X sequences collected from all major land plant lineages and show that this subfamily diversified into six major clades before the divergence between bryophytes and vascular plants. Notably, we have identified homologues of the brassinosteroid receptor, BRASSINOSTEROID INSENSITIVE 1 (BRI1), in the genomes of Sphagnum mosses, hornworts, and ferns, contrary to earlier reports that postulate the origin of BRI1-like LRR-RLKs in the seed plant lineage. The phylogenetic distribution of major clades illustrates that the current receptor repertoire was shaped through lineage-specific gene family expansion and independent gene losses, highlighting dynamic changes in the evolution of LRR-RLKs.}, } @article {pmid33373044, year = {2021}, author = {Montoro, R and Heine, VM and Kemp, S and Engelen, M}, title = {Evolution of adrenoleukodystrophy model systems.}, journal = {Journal of inherited metabolic disease}, volume = {44}, number = {3}, pages = {544-553}, pmid = {33373044}, issn = {1573-2665}, mesh = {ATP Binding Cassette Transporter, Subfamily D, Member 1/*genetics ; Adrenoleukodystrophy/epidemiology/*genetics ; Adult ; Animals ; Biological Evolution ; Fatty Acids/metabolism ; Female ; Humans ; Male ; *Models, Animal ; *Models, Biological ; Mutation ; Sex Factors ; Spinal Cord Diseases/epidemiology ; }, abstract = {X-linked adrenoleukodystrophy (ALD) is a neurometabolic disorder affecting the adrenal glands, testes, spinal cord and brain. The disease is caused by mutations in the ABCD1 gene resulting in a defect in peroxisomal degradation of very long-chain fatty acids and their accumulation in plasma and tissues. Males with ALD have a near 100% life-time risk to develop myelopathy. The life-time prevalence to develop progressive cerebral white matter lesions (known as cerebral ALD) is about 60%. Adrenal insufficiency occurs in about 80% of male patients. In adulthood, 80% of women with ALD also develop myelopathy, but adrenal insufficiency or cerebral ALD are very rare. The complex clinical presentation and the absence of a genotype-phenotype correlation are complicating our understanding of the disease. In an attempt to understand the pathophysiology of ALD various model systems have been developed. While these model systems share the basic genetics and biochemistry of ALD they fail to fully recapitulate the complex neurodegenerative etiology of ALD. Each model system recapitulates certain aspects of the disorder. This exposes the complexity of ALD and therefore the challenge to create a comprehensive model system to fully understand ALD. In this review, we provide an overview of the different ALD modeling strategies from single-celled to multicellular organisms and from in vitro to in vivo approaches, and introduce how emerging iPSC-derived technologies could improve the understanding of this highly complex disorder.}, } @article {pmid33355212, year = {2021}, author = {Stresser, DM and Sun, J and Wilson, SS}, title = {Evaluation of Tissue Stem Cell-Derived Human Intestinal Organoids, a Physiologically Relevant Model to Evaluate Cytochrome P450 Induction in Gut.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {49}, number = {3}, pages = {245-253}, doi = {10.1124/dmd.120.000281}, pmid = {33355212}, issn = {1521-009X}, mesh = {Cell Line ; Cytochrome P-450 Enzyme Inducers/*pharmacology ; Cytochrome P-450 Enzyme System/*biosynthesis ; Dose-Response Relationship, Drug ; Enzyme Induction/drug effects/physiology ; Humans ; Intestines/cytology/drug effects/*enzymology ; Organoids/drug effects/*enzymology ; Rifampin/pharmacology ; Stem Cells/drug effects/*enzymology ; }, abstract = {Induction of cytochrome P450 can cause drug-drug interactions and efficacy failure. Induction risk in liver and gut is typically inferred from experiments with plated hepatocytes. Organoids are physiologically relevant, multicellular structures originating from stem cells. Intestinal stem cell-derived organoids retain traits of normal gut physiology, such as an epithelial barrier and cellular diversity. Matched human enteroid and colonoid lines, generated from ileal and colon biopsies from two donors, were cultured in extracellular matrix for 3 days, followed by a single 48-hour treatment with rifampin, omeprazole, CITCO, and phenytoin at concentrations that induce target genes in hepatocytes. After treatment, mRNA was analyzed for induction of target genes. Rifampin induced CYP3A4; estimated EC50 and maximal fold induction were 3.75 µM and 8.96-fold, respectively, for ileal organoids and 1.40 µM and 11.3-fold, respectively, for colon organoids. Ileal, but not colon, organoids exhibited nifedipine oxidase activity, which was induced by rifampin up to 14-fold. The test compounds did not increase mRNA expression of CYP1A2, CYP2B6, multidrug resistance transporter 1 (P-glycoprotein), breast cancer resistance protein, and UDP-glucuronosyltransferase 1A1 in ileal organoids. Whereas omeprazole induced CYP3A4 (up to 5.3-fold, geometric mean, n = 4 experiments), constitutive androstane receptor activators phenytoin and CITCO did not. Omeprazole failed to induce CYP1A2 mRNA but did induce CYP1A1 mRNA (up to 7.7-fold and 15-fold in ileal and colon organoids, respectively, n = 4 experiments). Despite relatively high intra- and interexperimental variability, data suggest that the model yields induction responses that are distinct from hepatocytes and holds promise to enable evaluation of CYP1A1 and CYP3A4 induction in gut. SIGNIFICANCE STATEMENT: An adult intestinal stem cell-derived organoid model to test P450 induction in gut was evaluated. Testing several prototypical inducers for mRNA induction of P450 isoforms, UDP-glucuronosyltransferase 1A1, P-glycoprotein, and breast cancer resistance protein with both human colon and ileal organoids resulted in a range of responses, often distinct from those found in hepatocytes, indicating the potential for further development of this model as a physiologically relevant gut induction test system.}, } @article {pmid33354870, year = {2021}, author = {Fritsche, E and Haarmann-Stemmann, T and Kapr, J and Galanjuk, S and Hartmann, J and Mertens, PR and Kämpfer, AAM and Schins, RPF and Tigges, J and Koch, K}, title = {Stem Cells for Next Level Toxicity Testing in the 21st Century.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {17}, number = {15}, pages = {e2006252}, doi = {10.1002/smll.202006252}, pmid = {33354870}, issn = {1613-6829}, mesh = {Humans ; In Vitro Techniques ; *Induced Pluripotent Stem Cells ; *Toxicity Tests ; United States ; }, abstract = {The call for a paradigm change in toxicology from the United States National Research Council in 2007 initiates awareness for the invention and use of human-relevant alternative methods for toxicological hazard assessment. Simple 2D in vitro systems may serve as first screening tools, however, recent developments infer the need for more complex, multicellular organotypic models, which are superior in mimicking the complexity of human organs. In this review article most critical organs for toxicity assessment, i.e., skin, brain, thyroid system, lung, heart, liver, kidney, and intestine are discussed with regards to their functions in health and disease. Embracing the manifold modes-of-action how xenobiotic compounds can interfere with physiological organ functions and cause toxicity, the need for translation of such multifaceted organ features into the dish seems obvious. Currently used in vitro methods for toxicological applications and ongoing developments not yet arrived in toxicity testing are discussed, especially highlighting the potential of models based on embryonic stem cells and induced pluripotent stem cells of human origin. Finally, the application of innovative technologies like organs-on-a-chip and genome editing point toward a toxicological paradigm change moves into action.}, } @article {pmid33329717, year = {2020}, author = {Clairambault, J}, title = {Stepping From Modeling Cancer Plasticity to the Philosophy of Cancer.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {579738}, pmid = {33329717}, issn = {1664-8021}, } @article {pmid33329624, year = {2020}, author = {Lal, A and Vo, TTB and Sanjaya, IGNPW and Ho, PT and Kim, JK and Kil, EJ and Lee, S}, title = {Nanovirus Disease Complexes: An Emerging Threat in the Modern Era.}, journal = {Frontiers in plant science}, volume = {11}, number = {}, pages = {558403}, pmid = {33329624}, issn = {1664-462X}, abstract = {Multipartite viruses package their genomic segments independently and mainly infect plants; few target animals. Nanoviridae is a family of multipartite single-stranded DNA plant viruses that individually encapsidate single-stranded DNAs of approximately 1 kb and transmit them through aphids without replication in the aphid vectors, thereby causing important diseases of leguminous crops and banana. Significant findings regarding nanoviruses have recently been made on important features, such as their multicellular way of life, the transmission of distinct encapsidated genome segments through the vector body, evolutionary ambiguities, mode of infection, host range and geographical distribution. This review deals with all the above-mentioned features in view of recent advances with special emphasis on the emergence of new species and recognition of new host range of nanoviruses and aims to shed light on the evolutionary linkages, the potentially devastating impact on the world economy, and the future challenges imposed by nanoviruses.}, } @article {pmid33305692, year = {2020}, author = {Giam, M and Wong, CK and Low, JS and Sinelli, M and Dreesen, O and Rancati, G}, title = {P53 induces senescence in the unstable progeny of aneuploid cells.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {19}, number = {24}, pages = {3508-3520}, pmid = {33305692}, issn = {1551-4005}, mesh = {*Aneuploidy ; Cell Cycle Checkpoints/genetics ; Cell Proliferation/genetics ; Cell Transformation, Neoplastic/genetics/metabolism ; Cellular Senescence/*genetics ; Chromosomal Instability/genetics ; Chromosome Segregation/genetics ; Epithelial Cells/*metabolism ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Karyotype ; Retinal Pigment Epithelium/*cytology ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Aneuploidy is the condition of having an imbalanced karyotype, which is associated with tumor initiation, evolution, and acquisition of drug-resistant features, possibly by generating heterogeneous populations of cells with distinct genotypes and phenotypes. Multicellular eukaryotes have therefore evolved a range of extrinsic and cell-autonomous mechanisms for restraining proliferation of aneuploid cells, including activation of the tumor suppressor protein p53. However, accumulating evidence indicates that a subset of aneuploid cells can escape p53-mediated growth restriction and continue proliferating in vitro. Here we show that such aneuploid cell lines display a robust modal karyotype and low frequency of chromosomal aberrations despite ongoing chromosome instability. Indeed, while these aneuploid cells are able to survive for extended periods in vitro, their chromosomally unstable progeny remain subject to p53-induced senescence and growth restriction, leading to subsequent elimination from the aneuploid pool. This mechanism helps maintain low levels of heterogeneity in aneuploid populations and may prevent detrimental evolutionary processes such as cancer progression and development of drug resistance.}, } @article {pmid33292459, year = {2020}, author = {Zhang, J and Gu, C and Song, Q and Zhu, M and Xu, Y and Xiao, M and Zheng, W}, title = {Identifying cancer-associated fibroblasts as emerging targets for hepatocellular carcinoma.}, journal = {Cell & bioscience}, volume = {10}, number = {1}, pages = {127}, pmid = {33292459}, issn = {2045-3701}, support = {MS22018006//Nantong Science and Technology Bureau/ ; P30 DK058404/DK/NIDDK NIH HHS/United States ; BE2019692//Key Research and Development Program of Jiangxi Province/ ; 81702419//National Natural Science Foundation of China/ ; MS12019013//Nantong Science and Technology Bureau/ ; }, abstract = {The tumor microenvironment (TME) is a complex multicellular functional compartment that includes fibroblasts, myofibroblasts, endothelial cells, immune cells, and extracellular matrix (ECM) elements. The microenvironment provides an optimum condition for the initiation, growth, and dissemination of hepatocellular carcinoma (HCC). As one of the critical and abundant components in tumor microenvironment, cancer-associated fibroblasts (CAFs) have been implicated in the progression of HCC. Through secreting various growth factors and cytokines, CAFs contribute to the ECM remodeling, stem features, angiogenesis, immunosuppression, and vasculogenic mimicry (VM), which reinforce the initiation and development of HCC. In order to restrain the CAFs-initiated HCC progression, current strategies include targeting specific markers, engineering CAFs with tumor-suppressive phenotype, depleting CAFs' precursors, and repressing the secretions or downstream signaling. In this review, we update the emerging understanding of CAFs in HCC, with particular emphasis on cellular origin, phenotypes, biological functions and targeted strategies. It provides insights into the targeting CAFs for HCC treatment.}, } @article {pmid33272929, year = {2020}, author = {Ruiz-Trillo, I and de Mendoza, A}, title = {Towards understanding the origin of animal development.}, journal = {Development (Cambridge, England)}, volume = {147}, number = {23}, pages = {}, doi = {10.1242/dev.192575}, pmid = {33272929}, issn = {1477-9129}, mesh = {Animals ; *Biological Evolution ; Choanoflagellata/genetics/*growth & development ; Embryonic Development/*genetics ; Gene Expression Regulation, Developmental/genetics ; Mammals/genetics ; Morphogenesis/*genetics ; Phylogeny ; Zygote/growth & development ; }, abstract = {Almost all animals undergo embryonic development, going from a single-celled zygote to a complex multicellular adult. We know that the patterning and morphogenetic processes involved in development are deeply conserved within the animal kingdom. However, the origins of these developmental processes are just beginning to be unveiled. Here, we focus on how the protist lineages sister to animals are reshaping our view of animal development. Most intriguingly, many of these protistan lineages display transient multicellular structures, which are governed by similar morphogenetic and gene regulatory processes as animal development. We discuss here two potential alternative scenarios to explain the origin of animal embryonic development: either it originated concomitantly at the onset of animals or it evolved from morphogenetic processes already present in their unicellular ancestors. We propose that an integrative study of several unicellular taxa closely related to animals will allow a more refined picture of how the last common ancestor of animals underwent embryonic development.}, } @article {pmid33266251, year = {2020}, author = {Lyall, R and Nikoloski, Z and Gechev, T}, title = {Comparative Analysis of ROS Network Genes in Extremophile Eukaryotes.}, journal = {International journal of molecular sciences}, volume = {21}, number = {23}, pages = {}, pmid = {33266251}, issn = {1422-0067}, support = {SGA-CSA No. 739582//Project PlantaSYST, European Union's Horizon 2020 Research & Innovation Programme/ ; GA No. 823746//Project RESIST, European Union's Horizon 2020 Research & Innovation Programme/ ; BG05M2OP001-1.003-001-C01//European Regional Development Fund/ ; }, mesh = {Biomarkers ; Eukaryota/*genetics/*metabolism ; Extremophiles/*genetics/*metabolism ; Gene Expression Regulation ; Gene Expression Regulation, Enzymologic ; *Gene Regulatory Networks ; Oxidative Stress ; Plants/genetics/metabolism ; Reactive Oxygen Species/*metabolism ; }, abstract = {The reactive oxygen species (ROS) gene network, consisting of both ROS-generating and detoxifying enzymes, adjusts ROS levels in response to various stimuli. We performed a cross-kingdom comparison of ROS gene networks to investigate how they have evolved across all Eukaryotes, including protists, fungi, plants and animals. We included the genomes of 16 extremotolerant Eukaryotes to gain insight into ROS gene evolution in organisms that experience extreme stress conditions. Our analysis focused on ROS genes found in all Eukaryotes (such as catalases, superoxide dismutases, glutathione reductases, peroxidases and glutathione peroxidase/peroxiredoxins) as well as those specific to certain groups, such as ascorbate peroxidases, dehydroascorbate/monodehydroascorbate reductases in plants and other photosynthetic organisms. ROS-producing NADPH oxidases (NOX) were found in most multicellular organisms, although several NOX-like genes were identified in unicellular or filamentous species. However, despite the extreme conditions experienced by extremophile species, we found no evidence for expansion of ROS-related gene families in these species compared to other Eukaryotes. Tardigrades and rotifers do show ROS gene expansions that could be related to their extreme lifestyles, although a high rate of lineage-specific horizontal gene transfer events, coupled with recent tetraploidy in rotifers, could explain this observation. This suggests that the basal Eukaryotic ROS scavenging systems are sufficient to maintain ROS homeostasis even under the most extreme conditions.}, } @article {pmid33263876, year = {2020}, author = {Kaczanowski, S}, title = {Symbiotic Origin of Apoptosis.}, journal = {Results and problems in cell differentiation}, volume = {69}, number = {}, pages = {253-280}, pmid = {33263876}, issn = {0080-1844}, mesh = {Animals ; *Apoptosis ; *Biological Evolution ; *Eukaryota ; Mitochondria/*microbiology ; Phylogeny ; *Symbiosis ; }, abstract = {The progress of evolutionary biology has revealed that symbiosis played a basic role in the evolution of complex eukaryotic organisms, including humans. Mitochondria are actually simplified endosymbiotic bacteria currently playing the role of cellular organelles. Mitochondrial domestication occurred at the very beginning of eukaryotic evolution. Mitochondria have two different basic functions: they produce energy using oxidative respiration, and they initiate different forms of apoptotic programmed/regulated cell death. Apoptotic programmed cell death may have different cytological forms. Mechanisms of apoptotic programmed cell death exist even in the unicellular organisms, and they play a basic role in the development of complex multicellular organisms, such as fungi, green plants, and animals. Multicellularity was independently established many times among eukaryotes. There are indications that apoptotic programmed cell death is a trait required for the establishment of multicellularity. Regulated cell death is initiated by many different parallel biochemical pathways. It is generally accepted that apoptosis evolved during mitochondrial domestication. However, there are different hypothetical models of the origin of apoptosis. The phylogenetic studies of my group indicate that apoptosis probably evolved during an evolutionary arms race between host ancestral eukaryotic predators and ancestral prey mitochondria (named protomitochondria). Protomitochondrial prey produced many different toxins as a defense against predators. From these toxins evolved extant apoptotic factors. There are indications that aerobic respiration and apoptosis co-evolved and are functionally linked in extant organisms. Perturbations of apoptosis and oxidative respiration are frequently observed during neoplastic transition. Our group showed that perturbations of apoptosis in yeasts also cause perturbations of oxidative respiration.}, } @article {pmid33262337, year = {2020}, author = {McEvoy, E and Han, YL and Guo, M and Shenoy, VB}, title = {Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {6148}, pmid = {33262337}, issn = {2041-1723}, support = {R01 CA232256/CA/NCI NIH HHS/United States ; R01 EB017753/EB/NIBIB NIH HHS/United States ; R01 EB030876/EB/NIBIB NIH HHS/United States ; }, mesh = {Breast Neoplasms/chemistry/pathology/*physiopathology ; Cell Line, Tumor ; *Cell Proliferation ; Cell Size ; Disease Progression ; Female ; Gap Junctions/*chemistry ; Humans ; Osmotic Pressure ; Spheroids, Cellular/chemistry/*cytology ; }, abstract = {Sustained proliferation is a significant driver of cancer progression. Cell-cycle advancement is coupled with cell size, but it remains unclear how multiple cells interact to control their volume in 3D clusters. In this study, we propose a mechano-osmotic model to investigate the evolution of volume dynamics within multicellular systems. Volume control depends on an interplay between multiple cellular constituents, including gap junctions, mechanosensitive ion channels, energy-consuming ion pumps, and the actomyosin cortex, that coordinate to manipulate cellular osmolarity. In connected cells, we show that mechanical loading leads to the emergence of osmotic pressure gradients between cells with consequent increases in cellular ion concentrations driving swelling. We identify how gap junctions can amplify spatial variations in cell volume within multicellular spheroids and, further, describe how the process depends on proliferation-induced solid stress. Our model may provide new insight into the role of gap junctions in breast cancer progression.}, } @article {pmid33259762, year = {2020}, author = {König, SG and Nedelcu, AM}, title = {The genetic basis for the evolution of soma: mechanistic evidence for the co-option of a stress-induced gene into a developmental master regulator.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1940}, pages = {20201414}, pmid = {33259762}, issn = {1471-2954}, mesh = {*Biological Evolution ; Chlorophyta/*genetics ; Clonal Evolution/*genetics ; Stress, Physiological/*genetics ; }, abstract = {In multicellular organisms with specialized cells, the most significant distinction among cell types is between reproductive (germ) cells and non-reproductive/somatic cells (soma). Although soma contributed to the marked increase in complexity of many multicellular lineages, little is known about its evolutionary origins. We have previously suggested that the evolution of genes responsible for the differentiation of somatic cells involved the co-option of life history trade-off genes that in unicellular organisms enhanced survival at a cost to immediate reproduction. In the multicellular green alga, Volvox carteri, cell fate is established early in development by the differential expression of a master regulatory gene known as regA. A closely related RegA-Like Sequence (RLS1) is present in its single-celled relative, Chlamydomonas reinhardtii. RLS1 is expressed in response to stress, and we proposed that an environmentally induced RLS1-like gene was co-opted into a developmental pathway in the lineage leading to V. carteri. However, the exact evolutionary scenario responsible for the postulated co-option event remains to be determined. Here, we show that in addition to being developmentally regulated, regA can also be induced by environmental cues, indicating that regA has maintained its ancestral regulation. We also found that the absence of a functional RegA protein confers increased sensitivity to stress, consistent with RegA having a direct or indirect role in stress responses. Overall, this study (i) provides mechanistic evidence for the co-option of an environmentally induced gene into a major developmental regulator, (ii) supports the view that major morphological innovations can evolve via regulatory changes and (iii) argues for the role of stress in the evolution of multicellular complexity.}, } @article {pmid33254563, year = {2020}, author = {Retzinger, AC and Retzinger, GS}, title = {Mites, ticks, anaphylaxis and allergy: The Acari hypothesis.}, journal = {Medical hypotheses}, volume = {144}, number = {}, pages = {110257}, doi = {10.1016/j.mehy.2020.110257}, pmid = {33254563}, issn = {1532-2777}, mesh = {Allergens ; *Anaphylaxis ; Animals ; *Food Hypersensitivity ; Humans ; Immunoglobulin E ; *Mites ; *Ticks ; }, abstract = {Anaphylaxis is a poorly understood immune process in which a Th2-/IgE-mediated adaptive response commandeers cellular machinery, typically reserved for defense against multicellular ectoparasites, to activate against otherwise benign molecules. Its clinical manifestations consist of rapid pathophysiological reflexes that target epithelial surfaces. The galactose-α-1,3-galactose hypersensitivity response is a compelling model of anaphylaxis for which causation has been demonstrated. At the core of the model, a tick bite sensitizes a recipient to a tick foodstuff. As proposed herein, the model likely informs on the origin of all allergic inflammation; namely, allergy is not intended to protect against seemingly harmless and irrelevant materials, but is, instead, intended to rid epithelial surfaces of pathogen-bearing Acari, i.e., mites and ticks. The demonstrated adjuvant activity of acarian gastrointestinal secretions, when paired with the polyphagous diet of mites, renders acarians eminently suited to accounting, mechanistically, for many, if not all, human allergies.}, } @article {pmid33248278, year = {2020}, author = {Chi, S and Wang, G and Liu, T and Wang, X and Liu, C and Jin, Y and Yin, H and Xu, X and Yu, J}, title = {Transcriptomic and Proteomic Analysis of Mannitol-metabolism-associated Genes in Saccharina japonica.}, journal = {Genomics, proteomics & bioinformatics}, volume = {18}, number = {4}, pages = {415-429}, pmid = {33248278}, issn = {2210-3244}, mesh = {*Laminaria ; Mannitol ; *Phaeophyta/genetics ; Proteomics ; Transcriptome ; }, abstract = {As a carbon-storage compound and osmoprotectant in brown algae, mannitol is synthesized and then accumulated at high levels in Saccharina japonica (Sja); however, the underlying control mechanisms have not been studied. Our analysis of genomic and transcriptomic data from Sja shows that mannitol metabolism is a cyclic pathway composed of four distinct steps. A mannitol-1-phosphate dehydrogenase (M1PDH2) and two mannitol-1-phosphatases (M1Pase1 and MIPase2) work together or in combination to exhibit full enzymatic properties. Based on comprehensive transcriptomic data from different tissues, generations, and sexes as well as under different stress conditions, coupled with droplet digital PCR (ddPCR) and proteomic confirmation, we suggest that SjaM1Pase1 plays a major role in mannitol biosynthesis and that the basic mannitol anabolism and the carbohydrate pool dynamics are responsible for carbon storage and anti-stress mechanism. Our proteomic data indicate that mannitol metabolism remains constant during diurnal cycle in Sja. In addition, we discover that mannitol-metabolism-associated (MMA) genes show differential expression between the multicellular filamentous (gametophyte) and large parenchymal thallus (sporophyte) generations and respond differentially to environmental stresses, such as hyposaline and hyperthermia conditions. Our results indicate that the ecophysiological significance of such differentially expressed genes may be attributable to the evolution of heteromorphic generations (filamentous and thallus) and environmental adaptation of Laminariales.}, } @article {pmid33241195, year = {2020}, author = {Boutry, J and Dujon, AM and Gerard, AL and Tissot, S and Macdonald, N and Schultz, A and Biro, PA and Beckmann, C and Hamede, R and Hamilton, DG and Giraudeau, M and Ujvari, B and Thomas, F}, title = {Ecological and Evolutionary Consequences of Anticancer Adaptations.}, journal = {iScience}, volume = {23}, number = {11}, pages = {101716}, pmid = {33241195}, issn = {2589-0042}, abstract = {Cellular cheating leading to cancers exists in all branches of multicellular life, favoring the evolution of adaptations to avoid or suppress malignant progression, and/or to alleviate its fitness consequences. Ecologists have until recently largely neglected the importance of cancer cells for animal ecology, presumably because they did not consider either the potential ecological or evolutionary consequences of anticancer adaptations. Here, we review the diverse ways in which the evolution of anticancer adaptations has significantly constrained several aspects of the evolutionary ecology of multicellular organisms at the cell, individual, population, species, and ecosystem levels and suggest some avenues for future research.}, } @article {pmid33239636, year = {2020}, author = {Xu, Z and Wang, S and Zhao, C and Li, S and Liu, X and Wang, L and Li, M and Huang, X and Mann, S}, title = {Photosynthetic hydrogen production by droplet-based microbial micro-reactors under aerobic conditions.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5985}, pmid = {33239636}, issn = {2041-1723}, mesh = {Aerobiosis/physiology ; Bioreactors/*microbiology ; Cell Hypoxia/physiology ; Chlorella/metabolism ; Escherichia coli/metabolism ; Hydrogen/*metabolism ; Industrial Microbiology/*methods ; Microbiota/*physiology ; Oxygen/*metabolism ; Photosynthesis/physiology ; Renewable Energy ; }, abstract = {The spontaneous self-assembly of multicellular ensembles into living materials with synergistic structure and function remains a considerable challenge in biotechnology and synthetic biology. Here, we exploit the aqueous two-phase separation of dextran-in-PEG emulsion micro-droplets for the capture, spatial organization and immobilization of algal cells or algal/bacterial cell communities to produce discrete multicellular spheroids capable of both aerobic (oxygen producing) and hypoxic (hydrogen producing) photosynthesis in daylight under air. We show that localized oxygen depletion results in hydrogen production from the core of the algal microscale reactor, and demonstrate that enhanced levels of hydrogen evolution can be achieved synergistically by spontaneously enclosing the photosynthetic cells within a shell of bacterial cells undergoing aerobic respiration. Our results highlight a promising droplet-based environmentally benign approach to dispersible photosynthetic microbial micro-reactors comprising segregated cellular micro-niches with dual functionality, and provide a step towards photobiological hydrogen production under aerobic conditions.}, } @article {pmid33231627, year = {2021}, author = {Hammerschmidt, K and Landan, G and Domingues Kümmel Tria, F and Alcorta, J and Dagan, T}, title = {The Order of Trait Emergence in the Evolution of Cyanobacterial Multicellularity.}, journal = {Genome biology and evolution}, volume = {13}, number = {2}, pages = {}, pmid = {33231627}, issn = {1759-6653}, mesh = {Bacterial Proteins/classification ; Cyanobacteria/classification/cytology/*genetics/metabolism ; Ecosystem ; *Evolution, Molecular ; Nitrogen Fixation ; }, abstract = {The transition from unicellular to multicellular organisms is one of the most significant events in the history of life. Key to this process is the emergence of Darwinian individuality at the higher level: Groups must become single entities capable of reproduction for selection to shape their evolution. Evolutionary transitions in individuality are characterized by cooperation between the lower level entities and by division of labor. Theory suggests that division of labor may drive the transition to multicellularity by eliminating the trade off between two incompatible processes that cannot be performed simultaneously in one cell. Here, we examine the evolution of the most ancient multicellular transition known today, that of cyanobacteria, where we reconstruct the sequence of ecological and phenotypic trait evolution. Our results show that the prime driver of multicellularity in cyanobacteria was the expansion in metabolic capacity offered by nitrogen fixation, which was accompanied by the emergence of the filamentous morphology and succeeded by a reproductive life cycle. This was followed by the progression of multicellularity into higher complexity in the form of differentiated cells and patterned multicellularity.}, } @article {pmid33228413, year = {2020}, author = {Coelho, SM and Cock, JM}, title = {Brown Algal Model Organisms.}, journal = {Annual review of genetics}, volume = {54}, number = {}, pages = {71-92}, doi = {10.1146/annurev-genet-030620-093031}, pmid = {33228413}, issn = {1545-2948}, mesh = {Animals ; Genome/genetics ; Humans ; Models, Biological ; Phaeophyta/*genetics ; Phylogeny ; }, abstract = {Model organisms are extensively used in research as accessible and convenient systems for studying a particular area or question in biology. Traditionally, only a limited number of organisms have been studied in detail, but modern genomic tools are enabling researchers to extend beyond the set of classical model organisms to include novel species from less-studied phylogenetic groups. This review focuses on model species for an important group of multicellular organisms, the brown algae. The development of genetic and genomic tools for the filamentous brown alga Ectocarpus has led to it emerging as a general model system for this group, but additional models, such as Fucus or Dictyota dichotoma, remain of interest for specific biological questions. In addition, Saccharina japonica has emerged as a model system to directly address applied questions related to algal aquaculture. We discuss the past, present, and future of brown algal model organisms in relation to the opportunities and challenges in brown algal research.}, } @article {pmid33228223, year = {2020}, author = {Anatskaya, OV and Vinogradov, AE and Vainshelbaum, NM and Giuliani, A and Erenpreisa, J}, title = {Phylostratic Shift of Whole-Genome Duplications in Normal Mammalian Tissues towards Unicellularity Is Driven by Developmental Bivalent Genes and Reveals a Link to Cancer.}, journal = {International journal of molecular sciences}, volume = {21}, number = {22}, pages = {}, pmid = {33228223}, issn = {1422-0067}, support = {1.1.1.1/18/A/099//European Regional Development Fund (ERDF)/ ; 12//Institute of Cytology Director's Fund/ ; XX//Natural Sciences PhD Student Scholarship from the University of Latvia Foundation/ ; }, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Carcinogenesis/*genetics/metabolism/pathology ; Circadian Rhythm Signaling Peptides and Proteins/genetics/metabolism ; Drug Resistance, Neoplasm/genetics ; Epigenesis, Genetic ; Gene Duplication ; *Gene Expression Regulation, Neoplastic ; *Genome ; Humans ; Metabolic Networks and Pathways/genetics ; Mice ; Neoplasm Proteins/*genetics/metabolism ; Neoplasms/drug therapy/*genetics/metabolism/pathology ; Oncogenes ; *Ploidies ; Protein Interaction Mapping ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; }, abstract = {Tumours were recently revealed to undergo a phylostratic and phenotypic shift to unicellularity. As well, aggressive tumours are characterized by an increased proportion of polyploid cells. In order to investigate a possible shared causation of these two features, we performed a comparative phylostratigraphic analysis of ploidy-related genes, obtained from transcriptomic data for polyploid and diploid human and mouse tissues using pairwise cross-species transcriptome comparison and principal component analysis. Our results indicate that polyploidy shifts the evolutionary age balance of the expressed genes from the late metazoan phylostrata towards the upregulation of unicellular and early metazoan phylostrata. The up-regulation of unicellular metabolic and drug-resistance pathways and the downregulation of pathways related to circadian clock were identified. This evolutionary shift was associated with the enrichment of ploidy with bivalent genes (p < 10[-16]). The protein interactome of activated bivalent genes revealed the increase of the connectivity of unicellulars and (early) multicellulars, while circadian regulators were depressed. The mutual polyploidy-c-MYC-bivalent genes-associated protein network was organized by gene-hubs engaged in both embryonic development and metastatic cancer including driver (proto)-oncogenes of viral origin. Our data suggest that, in cancer, the atavistic shift goes hand-in-hand with polyploidy and is driven by epigenetic mechanisms impinging on development-related bivalent genes.}, } @article {pmid33216655, year = {2021}, author = {Snyder-Beattie, AE and Sandberg, A and Drexler, KE and Bonsall, MB}, title = {The Timing of Evolutionary Transitions Suggests Intelligent Life is Rare.}, journal = {Astrobiology}, volume = {21}, number = {3}, pages = {265-278}, pmid = {33216655}, issn = {1557-8070}, mesh = {Bayes Theorem ; Biological Evolution ; Earth, Planet ; *Exobiology ; Extraterrestrial Environment ; Intelligence ; *Planets ; }, abstract = {It is unknown how abundant extraterrestrial life is, or whether such life might be complex or intelligent. On Earth, the emergence of complex intelligent life required a preceding series of evolutionary transitions such as abiogenesis, eukaryogenesis, and the evolution of sexual reproduction, multicellularity, and intelligence itself. Some of these transitions could have been extraordinarily improbable, even in conducive environments. The emergence of intelligent life late in Earth's lifetime is thought to be evidence for a handful of rare evolutionary transitions, but the timing of other evolutionary transitions in the fossil record is yet to be analyzed in a similar framework. Using a simplified Bayesian model that combines uninformative priors and the timing of evolutionary transitions, we demonstrate that expected evolutionary transition times likely exceed the lifetime of Earth, perhaps by many orders of magnitude. Our results corroborate the original argument suggested by Brandon Carter that intelligent life in the Universe is exceptionally rare, assuming that intelligent life elsewhere requires analogous evolutionary transitions. Arriving at the opposite conclusion would require exceptionally conservative priors, evidence for much earlier transitions, multiple instances of transitions, or an alternative model that can explain why evolutionary transitions took hundreds of millions of years without appealing to rare chance events. Although the model is simple, it provides an initial basis for evaluating how varying biological assumptions and fossil record data impact the probability of evolving intelligent life, and also provides a number of testable predictions, such as that some biological paradoxes will remain unresolved and that planets orbiting M dwarf stars are uninhabitable.}, } @article {pmid33211685, year = {2020}, author = {Pichugin, Y and Traulsen, A}, title = {Evolution of multicellular life cycles under costly fragmentation.}, journal = {PLoS computational biology}, volume = {16}, number = {11}, pages = {e1008406}, pmid = {33211685}, issn = {1553-7358}, mesh = {*Biological Evolution ; Clostridiales/cytology/growth & development/physiology ; Computational Biology ; Cyanobacteria/cytology/growth & development/physiology ; Environment ; *Life Cycle Stages/physiology ; *Models, Biological ; Reproduction/physiology ; }, abstract = {A fascinating wealth of life cycles is observed in biology, from unicellularity to the concerted fragmentation of multicellular units. However, the understanding of factors driving their evolution is still limited. We show that costs of fragmentation have a major impact on the evolution of life cycles due to their influence on the growth rates of the associated populations. We model a group structured population of undifferentiated cells, where cell clusters reproduce by fragmentation. Fragmentation events are associated with a cost expressed by either a fragmentation delay, an additional risk, or a cell loss. The introduction of such fragmentation costs vastly increases the set of possible life cycles. Based on these findings, we suggest that the evolution of life cycles involving splitting into multiple offspring can be directly associated with the fragmentation cost. Moreover, the impact of this cost alone is strong enough to drive the emergence of multicellular units that eventually split into many single cells, even under scenarios that strongly disfavour collectives compared to solitary individuals.}, } @article {pmid33211684, year = {2020}, author = {Aubier, TG and Galipaud, M and Erten, EY and Kokko, H}, title = {Transmissible cancers and the evolution of sex under the Red Queen hypothesis.}, journal = {PLoS biology}, volume = {18}, number = {11}, pages = {e3000916}, pmid = {33211684}, issn = {1545-7885}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Genetics, Population/methods ; Host-Parasite Interactions/genetics ; Humans ; Models, Biological ; Models, Genetic ; Neoplasms/etiology/genetics ; Parasites ; Reproduction/*genetics/physiology ; Selection, Genetic/genetics/*physiology ; Sex ; }, abstract = {The predominance of sexual reproduction in eukaryotes remains paradoxical in evolutionary theory. Of the hypotheses proposed to resolve this paradox, the 'Red Queen hypothesis' emphasises the potential of antagonistic interactions to cause fluctuating selection, which favours the evolution and maintenance of sex. Whereas empirical and theoretical developments have focused on host-parasite interactions, the premises of the Red Queen theory apply equally well to any type of antagonistic interactions. Recently, it has been suggested that early multicellular organisms with basic anticancer defences were presumably plagued by antagonistic interactions with transmissible cancers and that this could have played a pivotal role in the evolution of sex. Here, we dissect this argument using a population genetic model. One fundamental aspect distinguishing transmissible cancers from other parasites is the continual production of cancerous cell lines from hosts' own tissues. We show that this influx dampens fluctuating selection and therefore makes the evolution of sex more difficult than in standard Red Queen models. Although coevolutionary cycling can remain sufficient to select for sex under some parameter regions of our model, we show that the size of those regions shrinks once we account for epidemiological constraints. Altogether, our results suggest that horizontal transmission of cancerous cells is unlikely to cause fluctuating selection favouring sexual reproduction. Nonetheless, we confirm that vertical transmission of cancerous cells can promote the evolution of sex through a separate mechanism, known as similarity selection, that does not depend on coevolutionary fluctuations.}, } @article {pmid33193544, year = {2020}, author = {Li, HJ and Yang, WC}, title = {Central Cell in Flowering Plants: Specification, Signaling, and Evolution.}, journal = {Frontiers in plant science}, volume = {11}, number = {}, pages = {590307}, pmid = {33193544}, issn = {1664-462X}, abstract = {During the reproduction of animals and lower plants, one sperm cell usually outcompetes the rivals to fertilize a single egg cell. But in flowering plants, two sperm cells fertilize the two adjacent dimorphic female gametes, the egg and central cell, respectively, to initiate the embryo and endosperm within a seed. The endosperm nourishes the embryo development and is also the major source of nutrition in cereals for humankind. Central cell as one of the key innovations of flowering plants is the biggest cell in the multicellular haploid female gametophyte (embryo sac). The embryo sac differentiates from the meiotic products through successive events of nuclear divisions, cellularization, and cell specification. Nowadays, accumulating lines of evidence are raveling multiple roles of the central cell rather than only the endosperm precursor. In this review, we summarize the current understanding on its cell fate specification, intercellular communication, and evolution. We also highlight some key unsolved questions for the further studies in this field.}, } @article {pmid33193180, year = {2020}, author = {Pessione, E}, title = {The Russian Doll Model: How Bacteria Shape Successful and Sustainable Inter-Kingdom Relationships.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {573759}, pmid = {33193180}, issn = {1664-302X}, abstract = {Successful inter-kingdom relationships are based upon a dynamic balance between defense and cooperation. A certain degree of competition is necessary to guarantee life spread and development. On the other hand, cooperation is a powerful tool to ensure a long lasting adaptation to changing environmental conditions and to support evolution to a higher level of complexity. Bacteria can interact with their (true or potential) parasites (i.e., phages) and with their multicellular hosts. In these model interactions, bacteria learnt how to cope with their inner and outer host, transforming dangerous signals into opportunities and modulating responses in order to achieve an agreement that is beneficial for the overall participants, thus giving rise to a more complex "organism" or ecosystem. In this review, particular attention will be addressed to underline the minimal energy expenditure required for these successful interactions [e.g., moonlighting proteins, post-translational modifications (PTMs), and multitasking signals] and the systemic vision of these processes and ways of life in which the system proves to be more than the sum of the single components. Using an inside-out perspective, I will examine the possibility of multilevel interactions, in which viruses help bacteria to cope with the animal host and bacteria support the human immune system to counteract viral infection in a circular vision. In this sophisticated network, bacteria represent the precious link that insures system stability with relative low energy expenditure.}, } @article {pmid35822167, year = {2020}, author = {Salnikov, L and Baramiya, MG}, title = {The Ratio of the Genome Two Functional Parts Activity as the Prime Cause of Aging.}, journal = {Frontiers in aging}, volume = {1}, number = {}, pages = {608076}, pmid = {35822167}, issn = {2673-6217}, abstract = {The metazoan genome composes of sets of housekeeping genes (HG) for fundamental cellular autonomous processes and integrative genes (IntG) that provide integrative functions and form the body as an integrated whole. The main paradigm for multicellularity development which has been improved in evolution, is the submission of the cellular autonomy to the interests of the integrated whole. Permanent increase of the "functional tax" of IntG-genome (IntG-shift) and epigenetic restriction of autonomy in phylogenesis/ontogenesis is the essence and root cause of aging, inherent in the very nature of highly integrated multicellularity. The regulation of the balance shift toward HG can be managed to eliminate aging and avoid carcinogenesis, which is only due to the irreversibility of this shift. Here we propose the criterion for measuring the functional and biological age of cells and the body as a whole for assessing the effectiveness of any type of palliative geroprotective or radical anti-aging intervention.}, } @article {pmid33184914, year = {2021}, author = {Castillo, SP and Keymer, JE and Marquet, PA}, title = {Do microenvironmental changes disrupt multicellular organisation with ageing, enacting and favouring the cancer cell phenotype?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {2}, pages = {e2000126}, doi = {10.1002/bies.202000126}, pmid = {33184914}, issn = {1521-1878}, mesh = {Aging ; Animals ; *Biological Evolution ; Ecosystem ; Humans ; *Neoplasms/genetics ; Phenotype ; }, abstract = {Cancer is a singular cellular state, the emergence of which destabilises the homeostasis reached through the evolution to multicellularity. We present the idea that the onset of the cellular disobedience to the metazoan functional and structural architecture, known as the cancer phenotype, is triggered by changes in the cell's external environment that occur with ageing: what ensues is a breach of the social contract of multicellular life characteristic of metazoans. By integrating old ideas with new evidence, we propose that with ageing the environmental information that maintains a multicellular organisation is eroded, rewiring internal processes of the cell, and resulting in an internal shift towards an ancestral condition resulting in the pseudo-multicellular cancer phenotype. Once that phenotype emerges, a new local social contract is built, different from the homeostatic one, leading to tumour formation and the foundation of a novel local ecosystem.}, } @article {pmid33180181, year = {2020}, author = {Konarska, A and Łotocka, B}, title = {Glandular trichomes of Robinia viscosa Vent. var. hartwigii (Koehne) Ashe (Faboideae, Fabaceae)-morphology, histochemistry and ultrastructure.}, journal = {Planta}, volume = {252}, number = {6}, pages = {102}, pmid = {33180181}, issn = {1432-2048}, mesh = {Flowers ; *Histocytochemistry ; Microscopy, Electron ; Plant Leaves ; *Robinia/chemistry/ultrastructure ; *Trichomes/chemistry/ultrastructure ; }, abstract = {Permanent glandular trichomes of Robinia viscosa var. hartwigii produce viscous secretion containing several secondary metabolites, as lipids, mucilage, flavonoids, proteins and alkaloids. Robinia viscosa var. hartwigii (Hartweg's locust) is an ornamental tree with high apicultural value. It can be planted in urban greenery and in degraded areas. The shoots, leaves, and inflorescences of this plant are equipped with numerous persistent glandular trichomes producing sticky secretion. The distribution, origin, development, morphology, anatomy, and ultrastructure of glandular trichomes of Hartweg's locust flowers as well as the localisation and composition of their secretory products were investigated for the first time. To this end, light, scanning, and transmission electron microscopy combined with histochemical and fluorescence techniques were used. The massive glandular trichomes differing in the distribution, length, and stage of development were built of a multicellular and multiseriate stalk and a multicellular head. The secretory cells in the stalk and head had large nuclei with nucleoli, numerous chloroplasts with thylakoids and starch grains, mitochondria, endoplasmic reticulum profiles, Golgi apparatus, vesicles, and multivesicular bodies. Many vacuoles contained phenolic compounds dissolved or forming various condensed deposits. The secretion components were transported through symplast elements, and the granulocrine and eccrine modes of nectar secretion were observed. The secretion was accumulated in the subcuticular space at the trichome apex and released through a pore in the cuticle. Histochemical and fluorescence assays showed that the trichomes and secretion contained lipophilic and polyphenol compounds, polysaccharides, proteins, and alkaloids. We suggest that these metabolites may serve an important function in protection of plants against biotic stress conditions and may also be a source of phytopharmaceuticals in the future.}, } @article {pmid33177521, year = {2020}, author = {Du, K and Luo, Q and Yin, L and Wu, J and Liu, Y and Gan, J and Dong, A and Shen, WH}, title = {OsChz1 acts as a histone chaperone in modulating chromatin organization and genome function in rice.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5717}, pmid = {33177521}, issn = {2041-1723}, mesh = {CRISPR-Cas Systems ; Chromatin/genetics/*metabolism ; DNA Methylation ; Flowers/metabolism ; Gene Expression Regulation, Plant ; Genome, Plant ; Histones/genetics/*metabolism ; Molecular Chaperones/genetics/metabolism ; Mutation ; Nucleosomes/genetics ; Oryza/*genetics/growth & development/metabolism ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Plants, Genetically Modified ; Protein Multimerization ; }, abstract = {While the yeast Chz1 acts as a specific histone-chaperone for H2A.Z, functions of CHZ-domain proteins in multicellular eukaryotes remain obscure. Here, we report on the functional characterization of OsChz1, a sole CHZ-domain protein identified in rice. OsChz1 interacts with both the canonical H2A-H2B dimer and the variant H2A.Z-H2B dimer. Within crystal structure the C-terminal region of OsChz1 binds H2A-H2B via an acidic region, pointing to a previously unknown recognition mechanism. Knockout of OsChz1 leads to multiple plant developmental defects. At genome-wide level, loss of OsChz1 causes mis-regulations of thousands of genes and broad alterations of nucleosome occupancy as well as reductions of H2A.Z-enrichment. While OsChz1 associates with chromatin regions enriched of repressive histone marks (H3K27me3 and H3K4me2), its loss does not affect the genome landscape of DNA methylation. Taken together, it is emerging that OsChz1 functions as an important H2A/H2A.Z-H2B chaperone in dynamic regulation of chromatin for higher eukaryote development.}, } @article {pmid33169570, year = {2020}, author = {Ma, X and Li, K and Wang, Z and Wei, D and Tang, Q}, title = {[Research progress in regulation model in different types of plant trichome].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {36}, number = {10}, pages = {2051-2065}, doi = {10.13345/j.cjb.200114}, pmid = {33169570}, issn = {1872-2075}, mesh = {Arabidopsis/genetics ; *Gene Expression Regulation, Plant ; Gossypium/genetics ; Solanum lycopersicum ; Plant Growth Regulators/genetics/metabolism ; *Trichomes/genetics ; }, abstract = {Plant trichomes are special structures that originate from epidermal outgrowths. Trichomes play an important role in plant defense against pests and diseases, and possess economic and medicinal values. Study on molecular mechanism of plant trichomes will contribute to the molecular design breeding and genetic improvement of crops. In recent years, the regulation mechanism of trichome development has been basically clarified in the model plant Arabidopsis thaliana, while great progresses are also found in other plant species. In this review, we focus on the developmental regulation of trichome formation from gene and phytohormones levels in Arabidopsis and cotton (with unicellular trichomes), as well as in tomato and Artemisia annua (with multicellular trichomes). The research progress associated with trichomes is also introduced in other typical monocotyledons and dicotyledons. Finally, the research and application of plant trichomes are prospected.}, } @article {pmid33165962, year = {2021}, author = {Blackstone, NW and Gutterman, JU}, title = {Can natural selection and druggable targets synergize? Of nutrient scarcity, cancer, and the evolution of cooperation.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {2}, pages = {e2000160}, doi = {10.1002/bies.202000160}, pmid = {33165962}, issn = {1521-1878}, mesh = {Animals ; *Biological Evolution ; Humans ; *Neoplasms/drug therapy ; Nutrients ; Selection, Genetic ; Symbiosis ; }, abstract = {Since the dawn of molecular biology, cancer therapy has focused on druggable targets. Despite some remarkable successes, cell-level evolution remains a potent antagonist to this approach. We suggest that a deeper understanding of the breakdown of cooperation can synergize the evolutionary and druggable-targets approaches. Complexity requires cooperation, whether between cells of different species (symbiosis) or between cells of the same organism (multicellularity). Both forms of cooperation may be associated with nutrient scarcity, which in turn may be associated with a chemiosmotic metabolism. A variety of examples from modern organisms supports these generalities. Indeed, mammalian cancers-unicellular, glycolytic, and fast-replicating-parallel these examples. Nutrient scarcity, chemiosmosis, and associated signaling may favor cooperation, while under conditions of nutrient abundance a fermentative metabolism may signal the breakdown of cooperation. Manipulating this metabolic milieu may potentiate the effects of targeted therapeutics. Specific opportunities are discussed in this regard, including avicins, a novel plant product.}, } @article {pmid33159138, year = {2020}, author = {Willman, S and Peel, JS and Ineson, JR and Schovsbo, NH and Rugen, EJ and Frei, R}, title = {Ediacaran Doushantuo-type biota discovered in Laurentia.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {647}, pmid = {33159138}, issn = {2399-3642}, mesh = {Animals ; *Biological Evolution ; *Biota ; *Fossils ; Geologic Sediments ; Greenland ; }, abstract = {The Ediacaran period (635-541 Ma) was a time of major environmental change, accompanied by a transition from a microbial world to the animal world we know today. Multicellular, macroscopic organisms preserved as casts and molds in Ediacaran siliciclastic rocks are preserved worldwide and provide snapshots of early organismal, including animal, evolution. Remarkable evolutionary advances are also witnessed by diverse cellular and subcellular phosphatized microfossils described from the Doushantuo Formation in China, the only source showing a diversified assemblage of microfossils. Here, we greatly extend the known distribution of this Doushantuo-type biota in reporting an Ediacaran Lagerstätte from Laurentia (Portfjeld Formation, North Greenland), with phosphatized animal-like eggs, embryos, acritarchs, and cyanobacteria, the age of which is constrained by the Shuram-Wonoka anomaly (c. 570-560 Ma). The discovery of these Ediacaran phosphatized microfossils from outside East Asia extends the distribution of the remarkable biota to a second palaeocontinent in the other hemisphere of the Ediacaran world, considerably expanding our understanding of the temporal and environmental distribution of organisms immediately prior to the Cambrian explosion.}, } @article {pmid33148926, year = {2020}, author = {Katoh, T and Satoh, M}, title = {[Environment and immunity-Allergies and autoimmune diseases from epidemiological perspective].}, journal = {Nihon eiseigaku zasshi. Japanese journal of hygiene}, volume = {75}, number = {0}, pages = {}, doi = {10.1265/jjh.20005}, pmid = {33148926}, issn = {1882-6482}, mesh = {Adolescent ; Adult ; Aged ; Autoantibodies ; Autoimmune Diseases/epidemiology/*immunology ; *Autoimmunity ; Biological Evolution ; Celiac Disease/immunology ; Child ; Child, Preschool ; Environment ; Female ; Humans ; Hypersensitivity/epidemiology/*immunology ; Infant ; Male ; Middle Aged ; Young Adult ; }, abstract = {Immunity, which denotes the protection of multicellular organisms against various bacterial and viral infections, is an essential protective mechanism for living organisms. Allergy is a reaction to a foreign substance existing in the environment that is basically not a component of the self. Additionally, autoimmune diseases are associated with the dysfunction in the recognition of self and non-self, and are pathological conditions caused by immune cells attacking their own tissues and cells. In this paper, we outline the current status of immunity with respect to the environment from the epidemiological perspective with regard to the following: (1) evolution and immunity, (2) allergy, (3) autoantibodies, (4) autoimmune diseases, (5) relationships of immunity with the environment, allergy, autoantibodies, and autoimmune diseases, and (6) celiac disease.}, } @article {pmid33143227, year = {2020}, author = {Petrushin, I and Belikov, S and Chernogor, L}, title = {Cooperative Interaction of Janthinobacterium sp. SLB01 and Flavobacterium sp. SLB02 in the Diseased Sponge Lubomirskia baicalensis.}, journal = {International journal of molecular sciences}, volume = {21}, number = {21}, pages = {}, pmid = {33143227}, issn = {1422-0067}, support = {19-14-00088//Russian Science Foundation/ ; 0345-2019-0002 (AAAA-A16-116122110066-1)//Siberian Branch, Russian Academy of Sciences/ ; }, mesh = {Animals ; Cooperative Behavior ; *Ecosystem ; Flavobacterium/*physiology ; Lakes ; Oxalobacteraceae/*physiology ; Phylogeny ; Porifera/*metabolism/*microbiology ; *Symbiosis ; }, abstract = {Endemic freshwater sponges (demosponges, Lubomirskiidae) dominate in Lake Baikal, Central Siberia, Russia. These sponges are multicellular filter-feeding animals that represent a complex consortium of many species of eukaryotes and prokaryotes. In recent years, mass disease and death of Lubomirskia baicalensis has been a significant problem in Lake Baikal. The etiology and ecology of these events remain unknown. Bacteria from the families Flavobacteriaceae and Oxalobacteraceae dominate the microbiomes of diseased sponges. Both species are opportunistic pathogens common in freshwater ecosystems. The aim of our study was to analyze the genomes of strains Janthinobacterium sp. SLB01 and Flavobacterium sp. SLB02, isolated from diseased sponges to identify the reasons for their joint dominance. Janthinobacterium sp. SLB01 attacks other cells using a type VI secretion system and suppresses gram-positive bacteria with violacein, and regulates its own activity via quorum sensing. It produces floc and strong biofilm by exopolysaccharide biosynthesis and PEP-CTERM/XrtA protein expression. Flavobacterium sp. SLB02 utilizes the fragments of cell walls produced by polysaccharides. These two strains have a marked difference in carbohydrate acquisition. We described a possible means of joint occupation of the ecological niche in the freshwater sponge microbial community. This study expands the understanding of the symbiotic relationship of microorganisms with freshwater Baikal sponges.}, } @article {pmid33142753, year = {2020}, author = {Burdukiewicz, M and Sidorczuk, K and Rafacz, D and Pietluch, F and Bąkała, M and Słowik, J and Gagat, P}, title = {CancerGram: An Effective Classifier for Differentiating Anticancer from Antimicrobial Peptides.}, journal = {Pharmaceutics}, volume = {12}, number = {11}, pages = {}, pmid = {33142753}, issn = {1999-4923}, support = {2017/26/D/NZ8/00444//Narodowym Centrum Nauki/ ; 2018/31/N/NZ2/01338//Narodowym Centrum Nauki/ ; 2019/35/N/NZ8/03366//Narodowym Centrum Nauki/ ; }, abstract = {Antimicrobial peptides (AMPs) constitute a diverse group of bioactive molecules that provide multicellular organisms with protection against microorganisms, and microorganisms with weaponry for competition. Some AMPs can target cancer cells; thus, they are called anticancer peptides (ACPs). Due to their small size, positive charge, hydrophobicity and amphipathicity, AMPs and ACPs interact with negatively charged components of biological membranes. AMPs preferentially permeabilize microbial membranes, but ACPs additionally target mitochondrial and plasma membranes of cancer cells. The preference towards mitochondrial membranes is explained by their membrane potential, membrane composition resulting from α-proteobacterial origin and the fact that mitochondrial targeting signals could have evolved from AMPs. Taking into account the therapeutic potential of ACPs and millions of deaths due to cancer annually, it is of vital importance to find new cationic peptides that selectively destroy cancer cells. Therefore, to reduce the costs of experimental research, we have created a robust computational tool, CancerGram, that uses n-grams and random forests for predicting ACPs. Compared to other ACP classifiers, CancerGram is the first three-class model that effectively classifies peptides into: ACPs, AMPs and non-ACPs/non-AMPs, with AU1U amounting to 0.89 and a Kappa statistic of 0.65. CancerGram is available as a web server and R package on GitHub.}, } @article {pmid33142097, year = {2020}, author = {Ostrowski, EA}, title = {Evolution of Multicellularity: One from Many or Many from One?.}, journal = {Current biology : CB}, volume = {30}, number = {21}, pages = {R1306-R1308}, doi = {10.1016/j.cub.2020.08.056}, pmid = {33142097}, issn = {1879-0445}, mesh = {*Biological Evolution ; }, abstract = {Multicellularity has evolved many times. A new study explores why some forms of multicellularity may be better than others.}, } @article {pmid33140720, year = {2020}, author = {Staps, M and Tarnita, C}, title = {How geometry shapes division of labor.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {33140720}, issn = {2050-084X}, mesh = {*Biological Evolution ; *Models, Biological ; Reproduction ; }, abstract = {A mathematical model shows how the shape of early multicellular organisms may have helped cells evolve specialized roles.}, } @article {pmid33138108, year = {2020}, author = {Ingargiola, C and Turqueto Duarte, G and Robaglia, C and Leprince, AS and Meyer, C}, title = {The Plant Target of Rapamycin: A Conduc TOR of Nutrition and Metabolism in Photosynthetic Organisms.}, journal = {Genes}, volume = {11}, number = {11}, pages = {}, pmid = {33138108}, issn = {2073-4425}, mesh = {Chlorophyta/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Metabolic Networks and Pathways ; Models, Biological ; Nitrogen/metabolism ; Phosphates/metabolism ; Photosynthesis ; Plant Development ; Plant Proteins/*metabolism ; Plants/*metabolism ; Potassium/metabolism ; Signal Transduction ; Stress, Physiological ; Sugars/metabolism ; Sulfur/metabolism ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {Living organisms possess many mechanisms to sense nutrients and favorable conditions, which allow them to grow and develop. Photosynthetic organisms are very diverse, from green unicellular algae to multicellular flowering plants, but most of them are sessile and thus unable to escape from the biotic and abiotic stresses they experience. The Target of Rapamycin (TOR) signaling pathway is conserved in all eukaryotes and acts as a central regulatory hub between growth and extrinsic factors, such as nutrients or stress. However, relatively little is known about the regulations and roles of this pathway in plants and algae. Although some features of the TOR pathway seem to have been highly conserved throughout evolution, others clearly differ in plants, perhaps reflecting adaptations to different lifestyles and the rewiring of this primordial signaling module to adapt to specific requirements. Indeed, TOR is involved in plant responses to a vast array of signals including nutrients, hormones, light, stresses or pathogens. In this review, we will summarize recent studies that address the regulations of TOR by nutrients in photosynthetic organisms, and the roles of TOR in controlling important metabolic pathways, highlighting similarities and differences with the other eukaryotes.}, } @article {pmid33126926, year = {2020}, author = {Lin, W and Zhang, W and Paterson, GA and Zhu, Q and Zhao, X and Knight, R and Bazylinski, DA and Roberts, AP and Pan, Y}, title = {Expanding magnetic organelle biogenesis in the domain Bacteria.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {152}, pmid = {33126926}, issn = {2049-2618}, mesh = {Bacteria/*classification/*cytology/genetics ; Ecosystem ; Genes, Bacterial/genetics ; Magnetosomes/genetics/*metabolism ; *Organelle Biogenesis ; *Phylogeny ; }, abstract = {BACKGROUND: The discovery of membrane-enclosed, metabolically functional organelles in Bacteria has transformed our understanding of the subcellular complexity of prokaryotic cells. Biomineralization of magnetic nanoparticles within magnetosomes by magnetotactic bacteria (MTB) is a fascinating example of prokaryotic organelles. Magnetosomes, as nano-sized magnetic sensors in MTB, facilitate cell navigation along the local geomagnetic field, a behaviour referred to as magnetotaxis or microbial magnetoreception. Recent discovery of novel MTB outside the traditionally recognized taxonomic lineages suggests that MTB diversity across the domain Bacteria are considerably underestimated, which limits understanding of the taxonomic distribution and evolutionary origin of magnetosome organelle biogenesis.

RESULTS: Here, we perform the most comprehensive metagenomic analysis available of MTB communities and reconstruct metagenome-assembled MTB genomes from diverse ecosystems. Discovery of MTB in acidic peatland soils suggests widespread MTB occurrence in waterlogged soils in addition to subaqueous sediments and water bodies. A total of 168 MTB draft genomes have been reconstructed, which represent nearly a 3-fold increase over the number currently available and more than double the known MTB species at the genome level. Phylogenomic analysis reveals that these genomes belong to 13 Bacterial phyla, six of which were previously not known to include MTB. These findings indicate a much wider taxonomic distribution of magnetosome organelle biogenesis across the domain Bacteria than previously thought. Comparative genome analysis reveals a vast diversity of magnetosome gene clusters involved in magnetosomal biogenesis in terms of gene content and synteny residing in distinct taxonomic lineages. Phylogenetic analyses of core magnetosome proteins in this largest available and taxonomically diverse dataset support an unexpectedly early evolutionary origin of magnetosome biomineralization, likely ancestral to the origin of the domain Bacteria.

CONCLUSIONS: These findings expand the taxonomic and phylogenetic diversity of MTB across the domain Bacteria and shed new light on the origin and evolution of microbial magnetoreception. Potential biogenesis of the magnetosome organelle in the close descendants of the last bacterial common ancestor has important implications for our understanding of the evolutionary history of bacterial cellular complexity and emphasizes the biological significance of the magnetosome organelle. Video Abstract.}, } @article {pmid33126770, year = {2020}, author = {Combarnous, Y and Nguyen, TMD}, title = {Cell Communications among Microorganisms, Plants, and Animals: Origin, Evolution, and Interplays.}, journal = {International journal of molecular sciences}, volume = {21}, number = {21}, pages = {}, pmid = {33126770}, issn = {1422-0067}, mesh = {Animals ; Bacteria/*metabolism ; *Biological Evolution ; *Cell Communication ; Fungi/*metabolism ; Phylogeny ; Plants/*metabolism ; Viruses/*metabolism ; }, abstract = {Cellular communications play pivotal roles in multi-cellular species, but they do so also in uni-cellular species. Moreover, cells communicate with each other not only within the same individual, but also with cells in other individuals belonging to the same or other species. These communications occur between two unicellular species, two multicellular species, or between unicellular and multicellular species. The molecular mechanisms involved exhibit diversity and specificity, but they share common basic features, which allow common pathways of communication between different species, often phylogenetically very distant. These interactions are possible by the high degree of conservation of the basic molecular mechanisms of interaction of many ligand-receptor pairs in evolutionary remote species. These inter-species cellular communications played crucial roles during Evolution and must have been positively selected, particularly when collectively beneficial in hostile environments. It is likely that communications between cells did not arise after their emergence, but were part of the very nature of the first cells. Synchronization of populations of non-living protocells through chemical communications may have been a mandatory step towards their emergence as populations of living cells and explain the large commonality of cell communication mechanisms among microorganisms, plants, and animals.}, } @article {pmid33126482, year = {2020}, author = {Kulkarni, P}, title = {Intrinsically Disordered Proteins: Insights from Poincaré, Waddington, and Lamarck.}, journal = {Biomolecules}, volume = {10}, number = {11}, pages = {}, pmid = {33126482}, issn = {2218-273X}, mesh = {*Biological Evolution ; Humans ; Intrinsically Disordered Proteins/chemistry/*genetics ; Phenotype ; *Protein Conformation ; }, abstract = {The past quarter-century may justly be referred to as a period analogous to the "Cambrian explosion" in the history of proteins. This period is marked by the appearance of the intrinsically disordered proteins (IDPs) on the scene since their discovery in the mid-1990s. Here, I first reflect on how we accidentally stumbled on these fascinating molecules. Next, I describe our research on the IDPs over the past decade and identify six areas as important for future research in this field. In addition, I draw on discoveries others in the field have made to present a more comprehensive essay. More specifically, I discuss the role of IDPs in two fundamental aspects of life: in phenotypic switching, and in multicellularity that marks one of the major evolutionary transitions. I highlight how serendipity, imagination, and an interdisciplinary approach embodying empirical evidence and theoretical insights from the works of Poincaré, Waddington, and Lamarck, shaped our thinking, and how this led us to propose the MRK hypothesis, a conceptual framework addressing phenotypic switching, the emergence of new traits, and adaptive evolution via nongenetic and IDP conformation-based mechanisms. Finally, I present a perspective on the evolutionary link between phenotypic switching and the origin of multicellularity.}, } @article {pmid33116351, year = {2020}, author = {Gu, X and Brennan, A and Wei, W and Guo, G and Lindsey, K}, title = {Vesicle Transport in Plants: A Revised Phylogeny of SNARE Proteins.}, journal = {Evolutionary bioinformatics online}, volume = {16}, number = {}, pages = {1176934320956575}, pmid = {33116351}, issn = {1176-9343}, abstract = {Communication systems within and between plant cells involve the transfer of ions and molecules between compartments, and are essential for development and responses to biotic and abiotic stresses. This in turn requires the regulated movement and fusion of membrane systems with their associated cargo. Recent advances in genomics has provided new resources with which to investigate the evolutionary relationships between membrane proteins across plant species. Members of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are known to play important roles in vesicle trafficking across plant, animal and microbial species. Using recent public expression and transcriptomic data from 9 representative green plants, we investigated the evolution of the SNARE classes and linked protein changes to functional specialization (expression patterns). We identified an additional 3 putative SNARE genes in the model plant Arabidopsis. We found that all SNARE classes have expanded in number to a greater or lesser degree alongside the evolution of multicellularity, and that within-species expansions are also common. These gene expansions appear to be associated with the accumulation of amino acid changes and with sub-functionalization of SNARE family members to different tissues. These results provide an insight into SNARE protein evolution and functional specialization. The work provides a platform for hypothesis-building and future research into the precise functions of these proteins in plant development and responses to the environment.}, } @article {pmid33097400, year = {2021}, author = {Véron, E and Vernoux, T and Coudert, Y}, title = {Phyllotaxis from a Single Apical Cell.}, journal = {Trends in plant science}, volume = {26}, number = {2}, pages = {124-131}, doi = {10.1016/j.tplants.2020.09.014}, pmid = {33097400}, issn = {1878-4372}, mesh = {*Bryopsida ; *Meristem/genetics ; Plant Leaves ; Plant Shoots ; }, abstract = {Phyllotaxis, the geometry of leaf arrangement around stems, determines plant architecture. Molecular interactions coordinating the formation of phyllotactic patterns have mainly been studied in multicellular shoot apical meristems of flowering plants. Phyllotaxis evolved independently in the major land plant lineages. In mosses, it arises from a single apical cell, raising the question of how asymmetric divisions of a single-celled meristem create phyllotactic patterns and whether associated genetic processes are shared across lineages. We present an overview of the mechanisms governing shoot apical cell specification and activity in the model moss, Physcomitrium patens, and argue that similar molecular regulatory modules have been deployed repeatedly across evolution to operate at different scales and drive apical function in convergent shoot forms.}, } @article {pmid33093150, year = {2020}, author = {Soubigou, A and Ross, EG and Touhami, Y and Chrismas, N and Modepalli, V}, title = {Regeneration in the sponge Sycon ciliatum partly mimics postlarval development.}, journal = {Development (Cambridge, England)}, volume = {147}, number = {22}, pages = {}, doi = {10.1242/dev.193714}, pmid = {33093150}, issn = {1477-9129}, mesh = {Animals ; Embryonic Development/*physiology ; Larva ; Porifera/*embryology ; Regeneration/*physiology ; Transcriptome/*physiology ; }, abstract = {Somatic cells dissociated from an adult sponge can reorganize and develop into a juvenile-like sponge, a remarkable phenomenon of regeneration. However, the extent to which regeneration recapitulates embryonic developmental pathways has remained enigmatic. We have standardized and established a sponge Sycon ciliatum regeneration protocol from dissociated cells. Morphological analysis demonstrated that dissociated sponge cells follow a series of morphological events resembling postembryonic development. We performed high-throughput sequencing on regenerating samples and compared the data with that from regular postlarval development. Our comparative transcriptomic analysis revealed that sponge regeneration is as equally dynamic as embryogenesis. We found that sponge regeneration is orchestrated by recruiting pathways similar to those utilized in embryonic development. We also demonstrated that sponge regeneration is accompanied by cell death at early stages, revealing the importance of apoptosis in remodelling the primmorphs to initiate re-development. Because sponges are likely to be the first branch of extant multicellular animals, we suggest that this system can be explored to study the genetic features underlying the evolution of multicellularity and regeneration.}, } @article {pmid33093080, year = {2020}, author = {Hammarlund, EU and Flashman, E and Mohlin, S and Licausi, F}, title = {Oxygen-sensing mechanisms across eukaryotic kingdoms and their roles in complex multicellularity.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6515}, pages = {}, doi = {10.1126/science.aba3512}, pmid = {33093080}, issn = {1095-9203}, mesh = {Anaerobiosis ; Animals ; Biological Evolution ; Dioxygenases/genetics/*metabolism ; Eukaryota/*classification/*metabolism ; Fungi ; Oxygen/*metabolism ; Plants ; }, abstract = {Oxygen-sensing mechanisms of eukaryotic multicellular organisms coordinate hypoxic cellular responses in a spatiotemporal manner. Although this capacity partly allows animals and plants to acutely adapt to oxygen deprivation, its functional and historical roots in hypoxia emphasize a broader evolutionary role. For multicellular life-forms that persist in settings with variable oxygen concentrations, the capacity to perceive and modulate responses in and between cells is pivotal. Animals and higher plants represent the most complex life-forms that ever diversified on Earth, and their oxygen-sensing mechanisms demonstrate convergent evolution from a functional perspective. Exploring oxygen-sensing mechanisms across eukaryotic kingdoms can inform us on biological innovations to harness ever-changing oxygen availability at the dawn of complex life and its utilization for their organismal development.}, } @article {pmid33081011, year = {2020}, author = {Steinberg, E and Orehov, N and Tischenko, K and Schwob, O and Zamir, G and Hubert, A and Manevitch, Z and Benny, O}, title = {Rapid Clearing for High Resolution 3D Imaging of Ex Vivo Pancreatic Cancer Spheroids.}, journal = {International journal of molecular sciences}, volume = {21}, number = {20}, pages = {}, pmid = {33081011}, issn = {1422-0067}, support = {0305260//Israel Science Foundation/ ; 0394906//Ministry of Science and Technology, Israel/ ; 0305260//H2020 European Research Council/ ; 3011004240//Israel Science Foundation/ ; }, mesh = {Cell Line, Tumor ; Extracellular Matrix/metabolism ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; *Imaging, Three-Dimensional ; Pancreatic Neoplasms/*diagnostic imaging/*pathology ; Spheroids, Cellular/*pathology ; Tumor Microenvironment ; }, abstract = {The currently accepted imaging methods have been a central hurdle to imaging the finer details of tumor behavior in three-dimensional (3D) ex vivo multicellular culture models. In our search for an improved way of imaging tumor behavior in its physiological-like niche, we developed a simple, efficient, and straightforward procedure using standard reagents and imaging equipment that significantly enhanced 3D imaging up to a ~200-micron depth. We tested its efficacy on pancreatic spheroids, prototypes of high-density tissues that are difficult to image. We found we could both save time with this method and extract information about pancreatic tumor spheroids that previously was difficult to obtain. We were able to discern clear differences in the organization of pancreatic tumor spheroids generated from different origins, suggesting cell-specific, inherent, bottom-up organization with a correlation to the level of malignancy. We also examined the dynamic changes in the spheroids at predetermined time points, providing important information related to tissue morphogenesis and its metabolic state. Lastly, this process enabled us to assess a drug vehicle's potential to penetrate dense tumor tissue by improving our view of the inert particles' diffusion in the 3D spheroid. This clearing method, a simple procedure, can open the door to more accurate imaging and reveal more about cancer behavior.}, } @article {pmid33072737, year = {2020}, author = {Teulière, J and Bernard, G and Bapteste, E}, title = {The Distribution of Genes Associated With Regulated Cell Death Is Decoupled From the Mitochondrial Phenotypes Within Unicellular Eukaryotic Hosts.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {536389}, pmid = {33072737}, issn = {2296-634X}, abstract = {Genetically regulated cell death (RCD) occurs in all domains of life. In eukaryotes, the evolutionary origin of the mitochondrion and of certain forms of RCD, in particular apoptosis, are thought to coincide, suggesting a central general role for mitochondria in cellular suicide. We tested this mitochondrial centrality hypothesis across a dataset of 67 species of protists, presenting 5 classes of mitochondrial phenotypes, including functional mitochondria, metabolically diversified mitochondria, functionally reduced mitochondria (Mitochondrion Related Organelle or MRO) and even complete absence of mitochondria. We investigated the distribution of genes associated with various forms of RCD. No homologs for described mammalian regulators of regulated necrosis could be identified in our set of 67 unicellular taxa. Protists with MRO and the secondarily a mitochondriate Monocercomonoides exilis display heterogeneous reductions of apoptosis gene sets with respect to typical mitochondriate protists. Remarkably, despite the total lack of mitochondria in M. exilis, apoptosis-associated genes could still be identified. These same species of protists with MRO and M. exilis harbored non-reduced autophagic cell death gene sets. Moreover, transiently multicellular protist taxa appeared enriched in apoptotic and autophagy associated genes compared to free-living protists. This analysis suggests that genes associated with apoptosis in animals and the presence of the mitochondria are significant yet non-essential biological components for RCD in protists. More generally, our results support the hypothesis of a selection for RCD, including both apoptosis and autophagy, as a developmental mechanism linked to multicellularity.}, } @article {pmid33068526, year = {2020}, author = {Palazzo, AF and Koonin, EV}, title = {Functional Long Non-coding RNAs Evolve from Junk Transcripts.}, journal = {Cell}, volume = {183}, number = {5}, pages = {1151-1161}, doi = {10.1016/j.cell.2020.09.047}, pmid = {33068526}, issn = {1097-4172}, support = {//CIHR/Canada ; }, mesh = {Animals ; DNA, Intergenic/genetics ; Enhancer Elements, Genetic/genetics ; Evolution, Molecular ; Humans ; RNA, Long Noncoding/*genetics/metabolism ; RNA, Messenger/*genetics/metabolism ; Transcription, Genetic ; }, abstract = {Transcriptome studies reveal pervasive transcription of complex genomes, such as those of mammals. Despite popular arguments for functionality of most, if not all, of these transcripts, genome-wide analysis of selective constraints indicates that most of the produced RNA are junk. However, junk is not garbage. On the contrary, junk transcripts provide the raw material for the evolution of diverse long non-coding (lnc) RNAs by non-adaptive mechanisms, such as constructive neutral evolution. The generation of many novel functional entities, such as lncRNAs, that fuels organismal complexity does not seem to be driven by strong positive selection. Rather, the weak selection regime that dominates the evolution of most multicellular eukaryotes provides ample material for functional innovation with relatively little adaptation involved.}, } @article {pmid33064719, year = {2020}, author = {Liu, XB and Xia, EH and Li, M and Cui, YY and Wang, PM and Zhang, JX and Xie, BG and Xu, JP and Yan, JJ and Li, J and Nagy, LG and Yang, ZL}, title = {Transcriptome data reveal conserved patterns of fruiting body development and response to heat stress in the mushroom-forming fungus Flammulina filiformis.}, journal = {PloS one}, volume = {15}, number = {10}, pages = {e0239890}, pmid = {33064719}, issn = {1932-6203}, mesh = {Agaricales/*genetics/growth & development/metabolism ; Conserved Sequence ; *Evolution, Molecular ; Fruiting Bodies, Fungal/genetics/*growth & development/metabolism ; Fungal Proteins/genetics/metabolism ; Heat-Shock Proteins/genetics/metabolism ; *Heat-Shock Response ; *Transcriptome ; }, abstract = {Mushroom-forming fungi are complex multicellular organisms that form the basis of a large industry, yet, our understanding of the mechanisms of mushroom development and its responses to various stresses remains limited. The winter mushroom (Flammulina filiformis) is cultivated at a large commercial scale in East Asia and is a species with a preference for low temperatures. This study investigated fruiting body development in F. filiformis by comparing transcriptomes of 4 developmental stages, and compared the developmental genes to a 200-genome dataset to identify conserved genes involved in fruiting body development, and examined the response of heat sensitive and -resistant strains to heat stress. Our data revealed widely conserved genes involved in primordium development of F. filiformis, many of which originated before the emergence of the Agaricomycetes, indicating co-option for complex multicellularity during evolution. We also revealed several notable fruiting-specific genes, including the genes with conserved stipe-specific expression patterns and the others which related to sexual development, water absorption, basidium formation and sporulation, among others. Comparative analysis revealed that heat stress induced more genes in the heat resistant strain (M1) than in the heat sensitive one (XR). Of particular importance are the hsp70, hsp90 and fes1 genes, which may facilitate the adjustment to heat stress in the early stages of fruiting body development. These data highlighted novel genes involved in complex multicellular development in fungi and aid further studies on gene function and efforts to improve the productivity and heat tolerance in mushroom-forming fungi.}, } @article {pmid33064078, year = {2020}, author = {Colizzi, ES and Vroomans, RM and Merks, RM}, title = {Evolution of multicellularity by collective integration of spatial information.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {33064078}, issn = {2050-084X}, support = {StartImpuls//Nederlands Wetenschap Agenda/International ; 865.17.004//NWO/ENW-VICI/International ; Nederlands Wetenschap Agenda StartImpuls//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/International ; NWO/ENW-VICI 865.17.004//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/International ; }, mesh = {*Biological Evolution ; Cell Adhesion ; *Cell Communication/physiology ; Chemotaxis/physiology ; Models, Biological ; }, abstract = {At the origin of multicellularity, cells may have evolved aggregation in response to predation, for functional specialisation or to allow large-scale integration of environmental cues. These group-level properties emerged from the interactions between cells in a group, and determined the selection pressures experienced by these cells. We investigate the evolution of multicellularity with an evolutionary model where cells search for resources by chemotaxis in a shallow, noisy gradient. Cells can evolve their adhesion to others in a periodically changing environment, where a cell's fitness solely depends on its distance from the gradient source. We show that multicellular aggregates evolve because they perform chemotaxis more efficiently than single cells. Only when the environment changes too frequently, a unicellular state evolves which relies on cell dispersal. Both strategies prevent the invasion of the other through interference competition, creating evolutionary bi-stability. Therefore, collective behaviour can be an emergent selective driver for undifferentiated multicellularity.}, } @article {pmid33062243, year = {2020}, author = {Arias Del Angel, JA and Nanjundiah, V and Benítez, M and Newman, SA}, title = {Interplay of mesoscale physics and agent-like behaviors in the parallel evolution of aggregative multicellularity.}, journal = {EvoDevo}, volume = {11}, number = {}, pages = {21}, pmid = {33062243}, issn = {2041-9139}, abstract = {Myxobacteria and dictyostelids are prokaryotic and eukaryotic multicellular lineages, respectively, that after nutrient depletion aggregate and develop into structures called fruiting bodies. The developmental processes and resulting morphological outcomes resemble one another to a remarkable extent despite their independent origins, the evolutionary distance between them and the lack of traceable homology in molecular mechanisms. We hypothesize that the morphological parallelism between the two lineages arises as the consequence of the interplay within multicellular aggregates between generic processes, physical and physicochemical processes operating similarly in living and non-living matter at the mesoscale (~10[-3]-10[-1] m) and agent-like behaviors, unique to living systems and characteristic of the constituent cells, considered as autonomous entities acting according to internal rules in a shared environment. Here, we analyze the contributions of generic and agent-like determinants in myxobacteria and dictyostelid development and their roles in the generation of their common traits. Consequent to aggregation, collective cell-cell contacts mediate the emergence of liquid-like properties, making nascent multicellular masses subject to novel patterning and morphogenetic processes. In both lineages, this leads to behaviors such as streaming, rippling, and rounding-up, as seen in non-living fluids. Later the aggregates solidify, leading them to exhibit additional generic properties and motifs. Computational models suggest that the morphological phenotypes of the multicellular masses deviate from the predictions of generic physics due to the contribution of agent-like behaviors of cells such as directed migration, quiescence, and oscillatory signal transduction mediated by responses to external cues. These employ signaling mechanisms that reflect the evolutionary histories of the respective organisms. We propose that the similar developmental trajectories of myxobacteria and dictyostelids are more due to shared generic physical processes in coordination with analogous agent-type behaviors than to convergent evolution under parallel selection regimes. Insights from the biology of these aggregative forms may enable a unified understanding of developmental evolution, including that of animals and plants.}, } @article {pmid33060828, year = {2021}, author = {Metcalfe, KS and Murali, R and Mullin, SW and Connon, SA and Orphan, VJ}, title = {Experimentally-validated correlation analysis reveals new anaerobic methane oxidation partnerships with consortium-level heterogeneity in diazotrophy.}, journal = {The ISME journal}, volume = {15}, number = {2}, pages = {377-396}, pmid = {33060828}, issn = {1751-7370}, mesh = {Anaerobiosis ; Archaea/genetics ; Costa Rica ; Geologic Sediments ; In Situ Hybridization, Fluorescence ; *Methane ; *Nitrogen Fixation ; Oxidation-Reduction ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Archaeal anaerobic methanotrophs ("ANME") and sulfate-reducing Deltaproteobacteria ("SRB") form symbiotic multicellular consortia capable of anaerobic methane oxidation (AOM), and in so doing modulate methane flux from marine sediments. The specificity with which ANME associate with particular SRB partners in situ, however, is poorly understood. To characterize partnership specificity in ANME-SRB consortia, we applied the correlation inference technique SparCC to 310 16S rRNA amplicon libraries prepared from Costa Rica seep sediment samples, uncovering a strong positive correlation between ANME-2b and members of a clade of Deltaproteobacteria we termed SEEP-SRB1g. We confirmed this association by examining 16S rRNA diversity in individual ANME-SRB consortia sorted using flow cytometry and by imaging ANME-SRB consortia with fluorescence in situ hybridization (FISH) microscopy using newly-designed probes targeting the SEEP-SRB1g clade. Analysis of genome bins belonging to SEEP-SRB1g revealed the presence of a complete nifHDK operon required for diazotrophy, unusual in published genomes of ANME-associated SRB. Active expression of nifH in SEEP-SRB1g within ANME-2b-SEEP-SRB1g consortia was then demonstrated by microscopy using hybridization chain reaction (HCR-) FISH targeting nifH transcripts and diazotrophic activity was documented by FISH-nanoSIMS experiments. NanoSIMS analysis of ANME-2b-SEEP-SRB1g consortia incubated with a headspace containing CH4 and [15]N2 revealed differences in cellular [15]N-enrichment between the two partners that varied between individual consortia, with SEEP-SRB1g cells enriched in [15]N relative to ANME-2b in one consortium and the opposite pattern observed in others, indicating both ANME-2b and SEEP-SRB1g are capable of nitrogen fixation, but with consortium-specific variation in whether the archaea or bacterial partner is the dominant diazotroph.}, } @article {pmid33060357, year = {2020}, author = {Toda, S and McKeithan, WL and Hakkinen, TJ and Lopez, P and Klein, OD and Lim, WA}, title = {Engineering synthetic morphogen systems that can program multicellular patterning.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6514}, pages = {327-331}, pmid = {33060357}, issn = {1095-9203}, support = {F32 DK123939/DK/NIDDK NIH HHS/United States ; R01 DE028496/DE/NIDCR NIH HHS/United States ; R35 DE026602/DE/NIDCR NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Body Patterning ; Drosophila melanogaster/growth & development ; Fibroblasts ; Green Fluorescent Proteins/genetics/*metabolism ; Protein Engineering ; Receptors, Notch/genetics/metabolism ; Tissue Engineering/*methods ; }, abstract = {In metazoan tissues, cells decide their fates by sensing positional information provided by specialized morphogen proteins. To explore what features are sufficient for positional encoding, we asked whether arbitrary molecules (e.g., green fluorescent protein or mCherry) could be converted into synthetic morphogens. Synthetic morphogens expressed from a localized source formed a gradient when trapped by surface-anchoring proteins, and they could be sensed by synthetic receptors. Despite their simplicity, these morphogen systems yielded patterns reminiscent of those observed in vivo. Gradients could be reshaped by altering anchor density or by providing a source of competing inhibitor. Gradient interpretation could be altered by adding feedback loops or morphogen cascades to receiver cell response circuits. Orthogonal cell-cell communication systems provide insight into morphogen evolution and a platform for engineering tissues.}, } @article {pmid33058872, year = {2020}, author = {Dyrka, W and Coustou, V and Daskalov, A and Lends, A and Bardin, T and Berbon, M and Kauffmann, B and Blancard, C and Salin, B and Loquet, A and Saupe, SJ}, title = {Identification of NLR-associated Amyloid Signaling Motifs in Bacterial Genomes.}, journal = {Journal of molecular biology}, volume = {432}, number = {23}, pages = {6005-6027}, doi = {10.1016/j.jmb.2020.10.004}, pmid = {33058872}, issn = {1089-8638}, mesh = {Amino Acid Motifs/genetics ; Amino Acid Sequence/genetics ; Amyloid/*genetics ; Amyloidogenic Proteins/genetics ; Animals ; Cyanobacteria/genetics ; Drosophila/genetics ; *Evolution, Molecular ; Fungi/genetics ; Genome, Bacterial/genetics ; Immunity, Innate/*genetics ; NLR Proteins/*genetics ; Prions/genetics ; Signal Transduction/genetics ; }, abstract = {In filamentous fungi, amyloid signaling sequences allow Nod-like receptors (NLRs) to activate downstream cell-death inducing proteins with HeLo and HeLo-like (HELL) domains and amyloid RHIM and RHIM-related motifs control immune defense pathways in mammals and flies. Herein, we show bioinformatically that analogous amyloid signaling motifs exist in bacteria. These short motifs are found at the N terminus of NLRs and at the C terminus of proteins with a domain we term BELL. The corresponding NLR and BELL proteins are encoded by adjacent genes. We identify 10 families of such bacterial amyloid signaling sequences (BASS), one of which (BASS3) is homologous to RHIM and a fungal amyloid motif termed PP. BASS motifs occur nearly exclusively in bacteria forming multicellular structures (mainly in Actinobacteria and Cyanobacteria). We analyze experimentally a subset of seven of these motifs (from the most common BASS1 family and the RHIM-related BASS3 family) and find that these sequences form fibrils in vitro. Using a fungal in vivo model, we show that all tested BASS-motifs form prions and that the NLR-side motifs seed prion-formation of the corresponding BELL-side motif. We find that BASS3 motifs show partial prion cross-seeding with mammalian RHIM and fungal PP-motifs and that proline mutations on key positions of the BASS3 core motif, conserved in RHIM and PP-motifs, abolish prion formation. This work expands the paradigm of prion amyloid signaling to multicellular prokaryotes and suggests a long-term evolutionary conservation of these motifs from bacteria, to fungi and animals.}, } @article {pmid33051374, year = {2020}, author = {Wright, RJ and Clegg, RJ and Coker, TLR and Kreft, JU}, title = {Damage Repair versus Aging in an Individual-Based Model of Biofilms.}, journal = {mSystems}, volume = {5}, number = {5}, pages = {}, pmid = {33051374}, issn = {2379-5077}, support = {NC/R001707/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; }, abstract = {The extent of senescence due to damage accumulation-or aging-is evidently evolvable as it differs hugely between species and is not universal, suggesting that its fitness advantages depend on life history and environment. In contrast, repair of damage is present in all organisms studied. Despite the fundamental trade-off between investing resources into repair or into growth, repair and segregation of damage have not always been considered alternatives. For unicellular organisms, unrepaired damage could be divided asymmetrically between daughter cells, leading to senescence of one and rejuvenation of the other. Repair of "unicells" has been predicted to be advantageous in well-mixed environments such as chemostats. Most microorganisms, however, live in spatially structured systems, such as biofilms, with gradients of environmental conditions and cellular physiology as well as a clonal population structure. To investigate whether this clonal structure might favor senescence by damage segregation (a division-of-labor strategy akin to the germline-soma division in multicellular organisms), we used an individual-based computational model and developed an adaptive repair strategy where cells respond to their current intracellular damage levels by investing into repair machinery accordingly. Our simulations showed that the new adaptive repair strategy was advantageous provided that growth was limited by substrate availability, which is typical for biofilms. Thus, biofilms do not favor a germline-soma-like division of labor between daughter cells in terms of damage segregation. We suggest that damage segregation is beneficial only when extrinsic mortality is high, a degree of multicellularity is present, and an active mechanism makes segregation effective.IMPORTANCE Damage is an inevitable consequence of life. For unicellular organisms, this leads to a trade-off between allocating resources into damage repair or into growth coupled with segregation of damage upon cell division, i.e., aging and senescence. Few studies considered repair as an alternative to senescence. None considered biofilms, where the majority of unicellular organisms live, although fitness advantages in well-mixed systems often turn into disadvantages in spatially structured systems such as biofilms. We compared the fitness consequences of aging versus an adaptive repair mechanism based on sensing damage, using an individual-based model of a generic unicellular organism growing in biofilms. We found that senescence is not beneficial provided that growth is limited by substrate availability. Instead, it is useful as a stress response to deal with damage that failed to be repaired when (i) extrinsic mortality was high; (ii) a degree of multicellularity was present; and (iii) damage segregation was effective.}, } @article {pmid33050851, year = {2020}, author = {Kurakin, GF and Samoukina, AM and Potapova, NA}, title = {Bacterial and Protozoan Lipoxygenases Could be Involved in Cell-to-Cell Signaling and Immune Response Suppression.}, journal = {Biochemistry. Biokhimiia}, volume = {85}, number = {9}, pages = {1048-1071}, doi = {10.1134/S0006297920090059}, pmid = {33050851}, issn = {1608-3040}, mesh = {Animals ; Bacteria/*enzymology ; *Biological Evolution ; *Cell Communication ; Humans ; Immunity/*immunology ; Lipoxygenases/*metabolism ; Protozoan Proteins/*metabolism ; }, abstract = {Lipoxygenases are found in animals, plants, and fungi, where they are involved in a wide range of cell-to-cell signaling processes. The presence of lipoxygenases in a number of bacteria and protozoa has been also established, but their biological significance remains poorly understood. Several hypothetical functions of lipoxygenases in bacteria and protozoa have been suggested without experimental validation. The objective of our study was evaluating the functions of bacterial and protozoan lipoxygenases by evolutionary and taxonomic analysis using bioinformatics tools. Lipoxygenase sequences were identified and examined using BLAST, followed by analysis of constructed phylogenetic trees and networks. Our results support the theory on the involvement of lipoxygenases in the formation of multicellular structures by microorganisms and their possible evolutionary significance in the emergence of multicellularity. Furthermore, we observed association of lipoxygenases with the suppression of host immune response by parasitic and symbiotic bacteria including dangerous opportunistic pathogens.}, } @article {pmid33036131, year = {2020}, author = {Dissanayake, L and Perera, P and Attanayaka, T and Heberle, E and Jayawardhana, M}, title = {Early Development of Direct Embryos in the Cultured Anthers of Manihot esculenta Crantz.}, journal = {Plants (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {33036131}, issn = {2223-7747}, support = {OPP1079312//Bill and Melinda Gates Foundation/ ; }, abstract = {Cassava is one of the most important sources of energy. To meet the growing demand, genetic improvement is of utmost importance. Its cross-pollinating nature limits the opportunity of exploitation of hybrid vigor and demands the development of homozygous lines through doubled-haploid technologies. The problems in callus-mediated embryogenesis, such as longer processing time and genetically unstable nature, can be overcome by direct embryogenesis. Conditions to produce embryos directly from microspores in cultured anthers were optimized. The optimum stress pretreatment condition was 40 °C for 6 h after culturing the anthers into the induction medium. For proembryo formation, 2% sucrose and 5 mg/l 2,4-dichlorophenoxyacetic acid (2,4-D) or 1 mg/l 1-naphthaleneacetic acid were optimum. Globular embryos were formed by subculturing proembryos into the medium with 0.5 mg/l 2,4-D and 5 mg/l 6-benzylaminopurine after two weeks of culturing. Light microscopy of cultured anthers demonstrated the formation of multicellular structures and their further development into proembryos. Microscopic studies showed proembryos emerging through the damaged anther wall. Monoallelic banding in simple sequence repeat (SSR) analysis indicated homozygous or haploid states in some of the originated embryos. The conditions optimized in this study were effective in the early development of direct embryos after two weeks of culture initiation. This is the first report of the formation of direct embryos in cultured anthers of cassava.}, } @article {pmid33035180, year = {2020}, author = {Essen, LO and Vogt, MS and Mösch, HU}, title = {Diversity of GPI-anchored fungal adhesins.}, journal = {Biological chemistry}, volume = {401}, number = {12}, pages = {1389-1405}, doi = {10.1515/hsz-2020-0199}, pmid = {33035180}, issn = {1437-4315}, mesh = {Cell Adhesion ; Glycosylphosphatidylinositols/*metabolism ; Saccharomyces cerevisiae/cytology/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {Selective adhesion of fungal cells to one another and to foreign surfaces is fundamental for the development of multicellular growth forms and the successful colonization of substrates and host organisms. Accordingly, fungi possess diverse cell wall-associated adhesins, mostly large glycoproteins, which present N-terminal adhesion domains at the cell surface for ligand recognition and binding. In order to function as robust adhesins, these glycoproteins must be covalently linkedto the cell wall via C-terminal glycosylphosphatidylinositol (GPI) anchors by transglycosylation. In this review, we summarize the current knowledge on the structural and functional diversity of so far characterized protein families of adhesion domains and set it into a broad context by an in-depth bioinformatics analysis using sequence similarity networks. In addition, we discuss possible mechanisms for the membrane-to-cell wall transfer of fungal adhesins by membrane-anchored Dfg5 transglycosidases.}, } @article {pmid33031891, year = {2021}, author = {Gao, JG}, title = {Tracking the evolutionary innovations of plant terrestrialization.}, journal = {Gene}, volume = {769}, number = {}, pages = {145203}, doi = {10.1016/j.gene.2020.145203}, pmid = {33031891}, issn = {1879-0038}, mesh = {*Biological Evolution ; Bryophyta/genetics/physiology ; Gene Transfer, Horizontal ; Genome, Plant ; *Plant Physiological Phenomena ; Plants/genetics ; }, abstract = {The gradual transition of the algal ancestor from the freshwater to land has always attracted evolutionary biologists. The recent report of high-quality reference genomes of five Charophyta algae (Spirogloea muscicola, Mesotaenium endlicherianum, Mesostigma viride, Chlorokybus atmophyticus and Penium margaritaceum) and one hornwort (Anthoceros angustus) species sheds light on this fascinating transition. These early diverging plants and algae could have gained new genes from soil bacteria and fungi through horizontal gene transfer (HGT), which was so common during plant terrestrialization and may outrun our expectations. Through reviewing and critical thinking about the advancements on these plant genomes, here, I propose three prospective research directions that need to address in the future: (i) due to the ubiquitous nature of viruses that is similar to soil bacteria and fungi, there is less attention to viruses that probably also play an important role in the genome evolution of plants via HGT; (ii) multicellularity has occurred many times independently, but we still know a little about the biological and ecological mechanisms leading to multi-cellularity in Streptophyta; (iii) and most importantly, the quantitative relationships between genetic innovations and environmental variables such as temperature, precipitation and solar radiation, need pioneering research collaborated by biological evolutionists, computer scientists, and ecologists, which are crucial for understanding the macroevolution of plants and could also be used to simulate the evolution of plants under future climate change.}, } @article {pmid33028229, year = {2020}, author = {Jiang, L and Lu, Y and Zheng, L and Li, G and Chen, L and Zhang, M and Ni, J and Liu, Q and Zhang, Y}, title = {The algal selenoproteomes.}, journal = {BMC genomics}, volume = {21}, number = {1}, pages = {699}, pmid = {33028229}, issn = {1471-2164}, support = {31401129//National Natural Science Foundation of China/ ; }, mesh = {Codon, Terminator ; *Eukaryota/genetics/metabolism ; Evolution, Molecular ; Proteome ; *Selenium ; Selenocysteine ; *Selenoproteins/genetics/metabolism ; }, abstract = {BACKGROUND: Selenium is an essential trace element, and selenocysteine (Sec, U) is its predominant form in vivo. Proteins that contain Sec are selenoproteins, whose special structural features include not only the TGA codon encoding Sec but also the SECIS element in mRNA and the conservation of the Sec-flanking region. These unique features have led to the development of a series of bioinformatics methods to predict and research selenoprotein genes. There have been some studies and reports on the evolution and distribution of selenoprotein genes in prokaryotes and multicellular eukaryotes, but the systematic analysis of single-cell eukaryotes, especially algae, has been very limited.

RESULTS: In this study, we predicted selenoprotein genes in 137 species of algae by using a program we previously developed. More than 1000 selenoprotein genes were obtained. A database website was built to record these algae selenoprotein genes (www.selenoprotein.com). These genes belong to 42 selenoprotein families, including three novel selenoprotein gene families.

CONCLUSIONS: This study reveals the primordial state of the eukaryotic selenoproteome. It is an important clue to explore the significance of selenium for primordial eukaryotes and to determine the complete evolutionary spectrum of selenoproteins in all life forms.}, } @article {pmid33024265, year = {2021}, author = {Ibrahim-Hashim, A and Luddy, K and Abrahams, D and Enriquez-Navas, P and Damgaci, S and Yao, J and Chen, T and Bui, MM and Gillies, RJ and O'Farrelly, C and Richards, CL and Brown, JS and Gatenby, RA}, title = {Artificial selection for host resistance to tumour growth and subsequent cancer cell adaptations: an evolutionary arms race.}, journal = {British journal of cancer}, volume = {124}, number = {2}, pages = {455-465}, pmid = {33024265}, issn = {1532-1827}, support = {P30 CA076292/CA/NCI NIH HHS/United States ; U54 CA143970/CA/NCI NIH HHS/United States ; R01 CA077575/CA/NCI NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*physiology ; Animals ; *Biological Evolution ; *Carcinoma, Lewis Lung ; Cell Plasticity/*physiology ; Disease Resistance/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, SCID ; }, abstract = {BACKGROUND: Cancer progression is governed by evolutionary dynamics in both the tumour population and its host. Since cancers die with the host, each new population of cancer cells must reinvent strategies to overcome the host's heritable defences. In contrast, host species evolve defence strategies over generations if tumour development limits procreation.

METHODS: We investigate this "evolutionary arms race" through intentional breeding of immunodeficient SCID and immunocompetent Black/6 mice to evolve increased tumour suppression. Over 10 generations, we injected Lewis lung mouse carcinoma cells [LL/2-Luc-M38] and selectively bred the two individuals with the slowest tumour growth at day 11. Their male progeny were hosts in the subsequent round.

RESULTS: The evolved SCID mice suppressed tumour growth through biomechanical restriction from increased mesenchymal proliferation, and the evolved Black/6 mice suppressed tumour growth by increasing immune-mediated killing of cancer cells. However, transcriptomic changes of multicellular tissue organisation and function genes allowed LL/2-Luc-M38 cells to adapt through increased matrix remodelling in SCID mice, and reduced angiogenesis, increased energy utilisation and accelerated proliferation in Black/6 mice.

CONCLUSION: Host species can rapidly evolve both immunologic and non-immunologic tumour defences. However, cancer cell plasticity allows effective phenotypic and population-based counter strategies.}, } @article {pmid33022031, year = {2020}, author = {Chambers, J and Sparks, N and Sydney, N and Livingstone, PG and Cookson, AR and Whitworth, DE}, title = {Comparative Genomics and Pan-Genomics of the Myxococcaceae, including a Description of Five Novel Species: Myxococcus eversor sp. nov., Myxococcus llanfairpwllgwyngyllgogerychwyrndrobwllllantysiliogogogochensis sp. nov., Myxococcus vastator sp. nov., Pyxidicoccus caerfyrddinensis sp. nov., and Pyxidicoccus trucidator sp. nov.}, journal = {Genome biology and evolution}, volume = {12}, number = {12}, pages = {2289-2302}, pmid = {33022031}, issn = {1759-6653}, mesh = {*Genome, Bacterial ; Genomics ; Myxococcales/*genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Members of the predatory Myxococcales (myxobacteria) possess large genomes, undergo multicellular development, and produce diverse secondary metabolites, which are being actively prospected for novel drug discovery. To direct such efforts, it is important to understand the relationships between myxobacterial ecology, evolution, taxonomy, and genomic variation. This study investigated the genomes and pan-genomes of organisms within the Myxococcaceae, including the genera Myxococcus and Corallococcus, the most abundant myxobacteria isolated from soils. Previously, ten species of Corallococcus were known, whereas six species of Myxococcus phylogenetically surrounded a third genus (Pyxidicoccus) composed of a single species. Here, we describe draft genome sequences of five novel species within the Myxococcaceae (Myxococcus eversor, Myxococcus llanfairpwllgwyngyllgogerychwyrndrobwllllantysiliogogogochensis, Myxococcus vastator, Pyxidicoccus caerfyrddinensis, and Pyxidicoccus trucidator) and for the Pyxidicoccus type species strain, Pyxidicoccus fallax DSM 14698T. Genomic and physiological comparisons demonstrated clear differences between the five novel species and every other Myxococcus or Pyxidicoccus spp. type strain. Subsequent analyses of type strain genomes showed that both the Corallococcus pan-genome and the combined Myxococcus and Pyxidicoccus (Myxococcus/Pyxidicoccus) pan-genome are large and open, but with clear differences. Genomes of Corallococcus spp. are generally smaller than those of Myxococcus/Pyxidicoccus spp. but have core genomes three times larger. Myxococcus/Pyxidicoccus spp. genomes are more variable in size, with larger and more unique sets of accessory genes than those of Corallococcus species. In both genera, biosynthetic gene clusters are relatively enriched in the shell pan-genomes, implying they grant a greater evolutionary benefit than other shell genes, presumably by conferring selective advantages during predation.}, } @article {pmid33016309, year = {2020}, author = {Gaisin, VA and Grouzdev, DS and Krutkina, MS and Ashikhmin, AA and Sinetova, MA and Osipova, NS and Koziaeva, VV and Gorlenko, VM}, title = {'Candidatus Oscillochloris kuznetsovii' a novel mesophilic filamentous anoxygenic phototrophic Chloroflexales bacterium from Arctic coastal environments.}, journal = {FEMS microbiology letters}, volume = {367}, number = {19}, pages = {}, doi = {10.1093/femsle/fnaa158}, pmid = {33016309}, issn = {1574-6968}, mesh = {Arctic Regions ; Chloroflexi/*classification/genetics/metabolism ; Environment ; Phototrophic Processes ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Species Specificity ; }, abstract = {Chloroflexales bacteria are mostly known as filamentous anoxygenic phototrophs that thrive as members of the microbial communities of hot spring cyanobacterial mats. Recently, we described many new Chloroflexales species from non-thermal environments and showed that mesophilic Chloroflexales are more diverse than previously expected. Most of these species were isolated from aquatic environments of mid-latitudes. Here, we present the comprehensive characterization of a new filamentous multicellular anoxygenic phototrophic Chloroflexales bacterium from an Arctic coastal environment (Kandalaksha Gulf, the White Sea). Phylogenomic analysis and 16S rRNA phylogeny indicated that this bacterium belongs to the Oscillochloridaceae family as a new species. We propose that this species be named 'Candidatus Oscillochloris kuznetsovii'. The genomes of this species possessed genes encoding sulfide:quinone reductase, the nitrogenase complex and the Calvin cycle, which indicate potential for photoautotrophic metabolism. We observed only mesophilic anaerobic anoxygenic phototrophic growth of this novel bacterium. Electron microphotography showed the presence of chlorosomes, polyhydroxyalkanoate-like granules and polyphosphate-like granules in the cells. High-performance liquid chromatography also revealed the presence of bacteriochlorophylls a, c and d as well as carotenoids. In addition, we found that this bacterium is present in benthic microbial communities of various coastal environments of the Kandalaksha Gulf.}, } @article {pmid33009502, year = {2020}, author = {Rochman, ND and Wolf, YI and Koonin, EV}, title = {Deep phylogeny of cancer drivers and compensatory mutations.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {551}, pmid = {33009502}, issn = {2399-3642}, mesh = {Animals ; Evolution, Molecular ; Genes, Neoplasm/*genetics ; Genes, Tumor Suppressor ; Humans ; Mutation/*genetics ; Neoplasms/*genetics ; Oncogenes/genetics ; Phylogeny ; Sequence Alignment ; }, abstract = {Driver mutations (DM) are the genetic impetus for most cancers. The DM are assumed to be deleterious in species evolution, being eliminated by purifying selection unless compensated by other mutations. We present deep phylogenies for 84 cancer driver genes and investigate the prevalence of 434 DM across gene-species trees. The DM are rare in species evolution, and 181 are completely absent, validating their negative fitness effect. The DM are more common in unicellular than in multicellular eukaryotes, suggesting a link between these mutations and cell proliferation control. 18 DM appear as the ancestral state in one or more major clades, including 3 among mammals. We identify within-gene, compensatory mutations for 98 DM and infer likely interactions between the DM and compensatory sites in protein structures. These findings elucidate the evolutionary status of DM and are expected to advance the understanding of the functions and evolution of oncogenes and tumor suppressors.}, } @article {pmid32991271, year = {2020}, author = {Michalakis, Y and Blanc, S}, title = {The Curious Strategy of Multipartite Viruses.}, journal = {Annual review of virology}, volume = {7}, number = {1}, pages = {203-218}, doi = {10.1146/annurev-virology-010220-063346}, pmid = {32991271}, issn = {2327-0578}, mesh = {DNA Viruses/genetics ; *Genome, Viral ; Humans ; Virion/genetics ; Virus Replication ; Viruses/*genetics ; }, abstract = {Multipartite virus genomes are composed of several segments, each packaged in a distinct viral particle. Although this puzzling genome architecture is found in ∼17% of known viral species, its distribution among hosts or among distinct types of genome-composing nucleic acid remains poorly understood. No convincing advantage of multipartitism has been identified, yet the maintenance of genomic integrity appears problematic. Here we review recent studies shedding light on these issues. Multipartite viruses rapidly modify the copy number of each segment/gene from one host species to another, a putative benefit if host switches are common. One multipartite virus functions in a multicellular way: The segments do not all need to be present in the same cell and can functionally complement across cells, maintaining genome integrity within hosts. The genomic integrity maintenance during host-to-host transmission needs further elucidation. These features challenge several virology foundations and could apply to other multicomponent viral systems.}, } @article {pmid32985765, year = {2021}, author = {Liu, P and Liu, Y and Zhao, X and Roberts, AP and Zhang, H and Zheng, Y and Wang, F and Wang, L and Menguy, N and Pan, Y and Li, J}, title = {Diverse phylogeny and morphology of magnetite biomineralized by magnetotactic cocci.}, journal = {Environmental microbiology}, volume = {23}, number = {2}, pages = {1115-1129}, doi = {10.1111/1462-2920.15254}, pmid = {32985765}, issn = {1462-2920}, support = {MGQNLM201704//Laboratory for Marine Geology, Qingdao National Laboratory for Marine Science and Technology/ ; 41621004//National Natural Science Foundation of China/ ; 41890843//National Natural Science Foundation of China/ ; 41920104009//National Natural Science Foundation of China/ ; RVKEXUE2019GZ06//The Senior User Project of RVKEXUE2019GZ06 (Center for Ocean Mega-Science, Chinese Academy of Sciences)/ ; DP200100765//Australian Research Council/ ; DP140104544//Australian Research Council/ ; }, mesh = {Alphaproteobacteria/*classification/cytology/genetics/*metabolism ; Biomineralization ; Ferrosoferric Oxide/*analysis/metabolism ; Geologic Sediments/microbiology ; Magnetosomes/chemistry/metabolism/ultrastructure ; *Phylogeny ; Species Specificity ; }, abstract = {Magnetotactic bacteria (MTB) are diverse prokaryotes that produce magnetic nanocrystals within intracellular membranes (magnetosomes). Here, we present a large-scale analysis of diversity and magnetosome biomineralization in modern magnetotactic cocci, which are the most abundant MTB morphotypes in nature. Nineteen novel magnetotactic cocci species are identified phylogenetically and structurally at the single-cell level. Phylogenetic analysis demonstrates that the cocci cluster into an independent branch from other Alphaproteobacteria MTB, that is, within the Etaproteobacteria class in the Proteobacteria phylum. Statistical analysis reveals species-specific biomineralization of magnetosomal magnetite morphologies. This further confirms that magnetosome biomineralization is controlled strictly by the MTB cell and differs among species or strains. The post-mortem remains of MTB are often preserved as magnetofossils within sediments or sedimentary rocks, yet paleobiological and geological interpretation of their fossil record remains challenging. Our results indicate that magnetofossil morphology could be a promising proxy for retrieving paleobiological information about ancient MTB.}, } @article {pmid32982686, year = {2020}, author = {Yamagata, M}, title = {Structure and Functions of Sidekicks.}, journal = {Frontiers in molecular neuroscience}, volume = {13}, number = {}, pages = {139}, pmid = {32982686}, issn = {1662-5099}, abstract = {Many of the immunoglobulin superfamily (IgSF) molecules play pivotal roles in cell communication. The Sidekick (Sdk) gene, first described in Drosophila, encodes the single-pass transmembrane protein, Sdk, which is one of the largest among IgSF membrane proteins. Sdk first appeared in multicellular animals during the Precambrian age and later evolved to Sdk1 and Sdk2 in vertebrates by gene duplication. In flies, a single Sdk is involved in positioning photoreceptor neurons and their axons in the visual system and is responsible for dynamically rearranging cell shapes by strictly populating tricellular adherens junctions in epithelia. In vertebrates, Sdk1 and Sdk2 are expressed by unique sets of cell types and distinctively participate in the formation and/or maintenance of neural circuits in the retina, indicating that they are determinants of synaptic specificity. These functions are mediated by specific homophilic binding of their ectodomains and by intracellular association with PDZ scaffold proteins. Recent human genetic studies as well as animal experiments implicate that Sdk genes may influence various neurodevelopmental and psychiatric disorders, such as autism spectrum disorders, attention-deficit hyperactivity disorder, addiction, and depression. The gigantic Sdk1 gene is susceptible to erratic gene rearrangements or mutations in both somatic and germ-line cells, potentially contributing to neurological disorders and some types of cancers. This review summarizes what is known about the structure and roles of Sdks.}, } @article {pmid32976811, year = {2020}, author = {Pande, S and Pérez Escriva, P and Yu, YN and Sauer, U and Velicer, GJ}, title = {Cooperation and Cheating among Germinating Spores.}, journal = {Current biology : CB}, volume = {30}, number = {23}, pages = {4745-4752.e4}, doi = {10.1016/j.cub.2020.08.091}, pmid = {32976811}, issn = {1879-0445}, mesh = {Betaine/*metabolism ; Myxococcus xanthus/*physiology ; Quorum Sensing/*physiology ; Soil Microbiology ; Spores, Bacterial/*growth & development ; }, abstract = {Many microbes produce stress-resistant spores to survive unfavorable conditions [1-4] and enhance dispersal [1, 5]. Cooperative behavior is integral to the process of spore formation in some species [3, 6], but the degree to which germination of spore populations involves social interactions remains little explored. Myxococcus xanthus is a predatory soil bacterium that upon starvation forms spore-filled multicellular fruiting bodies that often harbor substantial diversity of endemic origin [7, 8]. Here we demonstrate that germination of M. xanthus spores formed during fruiting-body development is a social process involving at least two functionally distinct social molecules. Using pairs of natural isolates each derived from a single fruiting body that emerged on soil, we first show that spore germination exhibits positive density dependence due to a secreted "public-good" germination factor. Further, we find that a germination defect of one strain under saline stress in pure culture is complemented by addition of another strain that germinates well in saline environments and mediates cheating by the defective strain. Glycine betaine, an osmo-protectant utilized in all domains of life, is found to mediate saline-specific density dependence and cheating. Density dependence in non-saline conditions is mediated by a distinct factor, revealing socially complex spore germination involving multiple social molecules.}, } @article {pmid32973760, year = {2020}, author = {Petre, B}, title = {Toward the Discovery of Host-Defense Peptides in Plants.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1825}, pmid = {32973760}, issn = {1664-3224}, mesh = {Antimicrobial Cationic Peptides/*metabolism ; Bacterial Infections/immunology/*metabolism/microbiology ; Botany ; Host-Pathogen Interactions ; *Plant Diseases/immunology/microbiology/virology ; Plant Immunity ; Plant Proteins/*metabolism ; Plants/immunology/*metabolism/microbiology/virology ; Research ; Signal Transduction ; Virus Diseases/immunology/*metabolism/virology ; }, abstract = {Defense peptides protect multicellular eukaryotes from infections. In biomedical sciences, a dominant conceptual framework refers to defense peptides as host-defense peptides (HDPs), which are bifunctional peptides with both direct antimicrobial and immunomodulatory activities. No HDP has been reported in plants so far, and the very concept of HDP has not been captured yet by the plant science community. Plant science thus lacks the conceptual framework that would coordinate research efforts aimed at discovering plant HDPs. In this perspective article, I used bibliometric and literature survey approaches to raise awareness about the HDP concept among plant scientists, and to encourage research efforts aimed at discovering plant HDPs. Such discovery would enrich our comprehension of the function and evolution of the plant immune system, and provide us with novel molecular tools to develop innovative strategies to control crop diseases.}, } @article {pmid32952610, year = {2020}, author = {Gatenby, RA and Avdieiev, S and Tsai, KY and Brown, JS}, title = {Integrating genetic and nongenetic drivers of somatic evolution during carcinogenesis: The biplane model.}, journal = {Evolutionary applications}, volume = {13}, number = {7}, pages = {1651-1659}, pmid = {32952610}, issn = {1752-4571}, support = {U54 CA143970/CA/NCI NIH HHS/United States ; }, abstract = {The multistep transition from a normal to a malignant cellular phenotype is often termed "somatic evolution" caused by accumulating random mutations. Here, we propose an alternative model in which the initial genetic state of a cancer cell is the result of mutations that occurred throughout the lifetime of the host. However, these mutations are not carcinogenic because normal cells in multicellular organism cannot ordinarily evolve. That is, proliferation and death of normal cells are controlled by local tissue constraints typically governed by nongenomic information dynamics in the cell membrane. As a result, the cells of a multicellular organism have a fitness that is identical to the host, which is then the unit of natural selection. Somatic evolution of a cell can occur only when its fate becomes independent of host constraints. Now, survival, proliferation, and death of individual cells are dependent on Darwinian dynamics. This cellular transition from host-defined fitness to self-defined fitness may, consistent with the conventional view of carcinogenesis, result from mutations that render the cell insensitive to host controls. However, an identical state will result when surrounding tissue cannot exert control because of injury, inflammation, aging, or infection. Here, all surviving cells within the site of tissue damage default to self-defined fitness functions allowing them to evolve so that the mutations accumulated over the lifetime of the host now serve as the genetic heritage of an evolutionary unit of selection. Furthermore, tissue injury generates a new ecology cytokines and growth factors that might promote proliferation in cells with prior receptor mutations. This model integrates genetic and nongenetic dynamics into cancer development and is consistent with both clinical observations and prior experiments that divided carcinogenesis to initiation, promotion, and progression steps.}, } @article {pmid32940598, year = {2020}, author = {Yanni, D and Jacobeen, S and Márquez-Zacarías, P and Weitz, JS and Ratcliff, WC and Yunker, PJ}, title = {Topological constraints in early multicellularity favor reproductive division of labor.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32940598}, issn = {2050-084X}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; R35 GM138354/GM/NIGMS NIH HHS/United States ; GM138030/NH/NIH HHS/United States ; }, mesh = {*Biological Evolution ; *Cell Communication ; Germ Cells ; Models, Biological ; *Reproduction ; }, abstract = {Reproductive division of labor (e.g. germ-soma specialization) is a hallmark of the evolution of multicellularity, signifying the emergence of a new type of individual and facilitating the evolution of increased organismal complexity. A large body of work from evolutionary biology, economics, and ecology has shown that specialization is beneficial when further division of labor produces an accelerating increase in absolute productivity (i.e. productivity is a convex function of specialization). Here we show that reproductive specialization is qualitatively different from classical models of resource sharing, and can evolve even when the benefits of specialization are saturating (i.e. productivity is a concave function of specialization). Through analytical theory and evolutionary individual-based simulations, we demonstrate that reproductive specialization is strongly favored in sparse networks of cellular interactions that reflect the morphology of early, simple multicellular organisms, highlighting the importance of restricted social interactions in the evolution of reproductive specialization.}, } @article {pmid32934242, year = {2020}, author = {Kinsella, CM and Bart, A and Deijs, M and Broekhuizen, P and Kaczorowska, J and Jebbink, MF and van Gool, T and Cotten, M and van der Hoek, L}, title = {Entamoeba and Giardia parasites implicated as hosts of CRESS viruses.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4620}, pmid = {32934242}, issn = {2041-1723}, mesh = {Adult ; Cohort Studies ; Entamoeba/*virology ; Feces/parasitology/virology ; Female ; Genome, Viral ; Giardia/*virology ; Host Specificity ; Humans ; Male ; Middle Aged ; Phylogeny ; Virus Physiological Phenomena ; Viruses/classification/genetics ; Young Adult ; }, abstract = {Metagenomic techniques have enabled genome sequencing of unknown viruses without isolation in cell culture, but information on the virus host is often lacking, preventing viral characterisation. High-throughput methods capable of identifying virus hosts based on genomic data alone would aid evaluation of their medical or biological relevance. Here, we address this by linking metagenomic discovery of three virus families in human stool samples with determination of probable hosts. Recombination between viruses provides evidence of a shared host, in which genetic exchange occurs. We utilise networks of viral recombination to delimit virus-host clusters, which are then anchored to specific hosts using (1) statistical association to a host organism in clinical samples, (2) endogenous viral elements in host genomes, and (3) evidence of host small RNA responses to these elements. This analysis suggests two CRESS virus families (Naryaviridae and Nenyaviridae) infect Entamoeba parasites, while a third (Vilyaviridae) infects Giardia duodenalis. The trio supplements five CRESS virus families already known to infect eukaryotes, extending the CRESS virus host range to protozoa. Phylogenetic analysis implies CRESS viruses infecting multicellular life have evolved independently on at least three occasions.}, } @article {pmid32931463, year = {2020}, author = {Cai, Y and Huang, J and Xu, H and Zhang, T and Cao, C and Pan, Y}, title = {Synthesis, characterization and application of magnetoferritin nanoparticle by using human H chain ferritin expressed by Pichia pastoris.}, journal = {Nanotechnology}, volume = {31}, number = {48}, pages = {485709}, doi = {10.1088/1361-6528/abb15d}, pmid = {32931463}, issn = {1361-6528}, mesh = {Animals ; Apoferritins/*analysis/genetics/toxicity/ultrastructure ; Fluorescent Dyes/*analysis/toxicity ; Gene Expression ; Humans ; Iron/*analysis/toxicity ; Nanoparticles/*analysis/ultrastructure ; Optical Imaging/*methods ; Oxides/*analysis/toxicity ; Rats, Sprague-Dawley ; Recombinant Proteins/analysis/genetics/toxicity/ultrastructure ; Saccharomycetales/genetics ; }, abstract = {Protein-based nanoparticles have developed rapidly in areas such as drug delivery, biomedical imaging and biocatalysis. Ferritin possesses unique properties that make it attractive as a potential platform for a variety of nanobiotechnological applications. Here we synthesized magnetoferritin (P-MHFn) nanoparticles for the first time by using the human H chain of ferritin that was expressed by Pichia pastoris (P-HFn). Western blot results showed that recombinant P-HFn was successfully expressed after methanol induction. Transmission electron microscopy (TEM) showed the spherical cage-like shape and monodispersion of P-HFn. The synthesized magnetoferritin (P-MHFn) retained the properties of magnetoferritin nanoparticles synthesized using HFn expressed by E. coli (E-MHFn): superparamagnetism under ambient conditions and peroxidase-like activity. It is stable under a wider range of pH values (from 5.0 to 11.0), likely due to post-translational modifications such as N-glycosylation on P-HFn. In vivo near-infrared fluorescence imaging experiments revealed that P-MHFn nanoparticles can accumulate in tumors, which suggests that P-MHFn could be used in tumor imaging and therapy. An acute toxicity study of P-MHFn in Sprague Dawley rats showed no abnormalities at a dose up to 20 mg Fe Kg[-1] body weight. Therefore, this study shed light on the development of magnetoferritin nanoparticles using therapeutic HFn expressed by Pichia pastoris for biomedical applications.}, } @article {pmid32930360, year = {2021}, author = {Salas-Vidal, E and Méndez-Cruz, FJ and Ramírez-Corona, A and Reza-Medina, B}, title = {Oxygen, reactive oxygen species and developmental redox networks: Evo-Devo Evil-Devils?.}, journal = {The International journal of developmental biology}, volume = {65}, number = {4-5-6}, pages = {345-356}, doi = {10.1387/ijdb.200170es}, pmid = {32930360}, issn = {1696-3547}, mesh = {Animals ; *Biological Evolution ; *Developmental Biology ; Oxidation-Reduction ; *Oxygen ; *Reactive Oxygen Species ; }, abstract = {Molecular oxygen (O2), reactive oxygen species (ROS), and associated redox networks are cornerstones of aerobic life. These molecules and networks have gained recognition as fundamental players in mechanisms that regulate the development of multicellular organisms. First, we present a brief review in which we provide a historical description of some relevant discoveries that led to this recognition. We also discuss the fact that, despite its abundance in nature, oxygen is a limiting factor, and its high availability variation impacted the evolution of adaptive mechanisms to guarantee the proper development of diverse species under such extreme environments. Finally, some examples of when oxygen and ROS were identified as relevant for the control of developmental processes are discussed. We take into account not only the current knowledge on animal redox developmental biology, but also briefly discuss potential scenarios on the origin and evolution of redox developmental mechanisms and the importance of the ever-changing environment.}, } @article {pmid32929605, year = {2020}, author = {Cui, Y and Zhao, H and Wu, S and Li, X}, title = {Human Female Reproductive System Organoids: Applications in Developmental Biology, Disease Modelling, and Drug Discovery.}, journal = {Stem cell reviews and reports}, volume = {16}, number = {6}, pages = {1173-1184}, doi = {10.1007/s12015-020-10039-0}, pmid = {32929605}, issn = {2629-3277}, mesh = {Animals ; *Developmental Biology ; Disease Models, Animal ; *Drug Discovery ; Female ; Genitalia, Female/*pathology ; Humans ; Organoids/*pathology ; Trophoblasts/pathology ; }, abstract = {Organoid technique has achieved significant progress in recent years, owing to the rapid development of the three-dimensional (3D) culture techniques in adult stem cells (ASCs) and pluripotent stem cells (PSCs) that are capable of self-renewal and induced differentiation. However, our understanding of human female reproductive system organoids is in its infancy. Recently, scientists have established self-organizing 3D organoids for human endometrium, fallopian tubes, oocyte, and trophoblasts by culturing stem cells with a cocktail of cytokines in a 3D scaffold. These organoids express multicellular biomarkers and show functional characteristics similar to those of their origin organs, which provide potential avenues to explore reproductive system development, disease modelling, and patient-specific therapy. Nevertheless, advanced culture methods, such as co-culture system, 3D bioprinting and organoid-on-a-chip technology, remain to be explored, and more efforts should be made for further elucidation of cell-cell crosstalk. This review describes the development and applications of human female reproductive system organoids. Graphical abstract Figure: Applications in developmental biology, disease modelling, and drug discovery of human female reproductive system organoids. ASCs: adult stem cells; PSCs: pluripotent stem cells.}, } @article {pmid32929365, year = {2020}, author = {Mowday, AM and Copp, JN and Syddall, SP and Dubois, LJ and Wang, J and Lieuwes, NG and Biemans, R and Ashoorzadeh, A and Abbattista, MR and Williams, EM and Guise, CP and Lambin, P and Ackerley, DF and Smaill, JB and Theys, J and Patterson, AV}, title = {E. coli nitroreductase NfsA is a reporter gene for non-invasive PET imaging in cancer gene therapy applications.}, journal = {Theranostics}, volume = {10}, number = {23}, pages = {10548-10562}, pmid = {32929365}, issn = {1838-7640}, mesh = {Animals ; Antineoplastic Agents, Alkylating/*pharmacology/therapeutic use ; Drug Resistance, Neoplasm ; Escherichia coli Proteins/*administration & dosage/genetics ; Etanidazole/administration & dosage/analogs & derivatives/pharmacokinetics ; *Genes, Reporter ; Genetic Therapy ; Genetic Vectors/administration & dosage/pharmacokinetics ; HCT116 Cells ; Humans ; Hydrocarbons, Fluorinated/administration & dosage/pharmacokinetics ; Imidazoles/administration & dosage ; Indicators and Reagents/administration & dosage/pharmacokinetics ; Mice ; Molecular Imaging/methods ; Neoplasms/*diagnostic imaging/drug therapy/genetics/pathology ; Nitrogen Mustard Compounds/pharmacology/therapeutic use ; Nitroreductases/*administration & dosage/genetics ; Positron-Emission Tomography/*methods ; Precision Medicine/methods ; Proof of Concept Study ; Radiopharmaceuticals/administration & dosage ; Recombinant Proteins/administration & dosage/genetics ; Triazoles/administration & dosage ; Tumor Hypoxia ; Xenograft Model Antitumor Assays ; }, abstract = {The use of reporter genes to non-invasively image molecular processes inside cells has significant translational potential, particularly in the context of systemically administered gene therapy vectors and adoptively administered cells such as immune or stem cell based therapies. Bacterial nitroreductase enzymes possess ideal properties for reporter gene imaging applications, being of non-human origin and possessing the ability to metabolize a range of clinically relevant nitro(hetero)cyclic substrates. Methods: A library of eleven Escherichia coli nitroreductase candidates were screened for the ability to efficiently metabolize 2-nitroimidazole based positron emission tomography (PET) probes originally developed as radiotracers for hypoxic cell imaging. Several complementary methods were utilized to detect formation of cell-entrapped metabolites, including various in vitro and in vivo models to establish the capacity of the 2-nitroimidazole PET agent EF5 to quantify expression of a nitroreductase candidate. Proof-of-principle PET imaging studies were successfully conducted using [18]F-HX4. Results: Recombinant enzyme kinetics, bacterial SOS reporter assays, anti-proliferative assays and flow cytometry approaches collectively identified the major oxygen-insensitive nitroreductase NfsA from E. coli (NfsA_Ec) as the most promising nitroreductase reporter gene. Cells expressing NfsA_Ec were demonstrably labelled with the imaging agent EF5 in a manner that was quantitatively superior to hypoxia, in monolayers (2D), multicellular layers (3D), and in human tumor xenograft models. EF5 retention correlated with NfsA_Ec positive cell density over a range of EF5 concentrations in 3D in vitro models and in xenografts in vivo and was predictive of in vivo anti-tumor activity of the cytotoxic prodrug PR-104. Following PET imaging with [18]F-HX4, a significantly higher tumor-to-blood ratio was observed in two xenograft models for NfsA_Ec expressing tumors compared to the parental tumors thereof, providing verification of this reporter gene imaging approach. Conclusion: This study establishes that the bacterial nitroreductase NfsA_Ec can be utilized as an imaging capable reporter gene, with the ability to metabolize and trap 2-nitroimidazole PET imaging agents for non-invasive imaging of gene expression.}, } @article {pmid32802320, year = {2020}, author = {Cohen, IR and Marron, A}, title = {The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {626}, pmid = {32802320}, issn = {2046-1402}, mesh = {*Adaptation, Biological ; Animals ; *Entropy ; Humans ; Metabolic Networks and Pathways ; Microbiota ; Phenotype ; *Reproduction ; }, abstract = {The evolution of multicellular eukaryotes expresses two sorts of adaptations: local adaptations like fur or feathers, which characterize species in particular environments, and universal adaptations like microbiomes or sexual reproduction, which characterize most multicellulars in any environment. We reason that the mechanisms driving the universal adaptations of multicellulars should themselves be universal, and propose a mechanism based on properties of matter and systems: energy, entropy, and interaction. Energy from the sun, earth and beyond creates new arrangements and interactions. Metabolic networks channel some of this energy to form cooperating, interactive arrangements. Entropy, used here as a term for all forces that dismantle ordered structures (rather than as a physical quantity), acts as a selective force. Entropy selects for arrangements that resist it long enough to replicate, and dismantles those that do not. Interactions, energy-charged and dynamic, restrain entropy and enable survival and propagation of integrated living systems. This fosters survival-of-the-fitted - those entities that resist entropic destruction - and not only of the fittest - the entities with the greatest reproductive success. The "unit" of evolution is not a discrete entity, such as a gene, individual, or species; what evolves are collections of related interactions at multiple scales. Survival-of-the-fitted explains universal adaptations, including resident microbiomes, sexual reproduction, continuous diversification, programmed turnover, seemingly wasteful phenotypes, altruism, co-evolving environmental niches, and advancing complexity. Indeed survival-of-the-fittest may be a particular case of the survival-of-the-fitted mechanism, promoting local adaptations that express reproductive advantages in addition to resisting entropy. Survival-of-the-fitted accounts for phenomena that have been attributed to neutral evolution: in the face of entropy, there is no neutrality; all variations are challenged by ubiquitous energy and entropy, retaining those that are "fit enough". We propose experiments to test predictions of the survival-of-the-fitted theory, and discuss implications for the wellbeing of humans and the biosphere.}, } @article {pmid32918875, year = {2020}, author = {Funato, Y and Yoshida, A and Hirata, Y and Hashizume, O and Yamazaki, D and Miki, H}, title = {The Oncogenic PRL Protein Causes Acid Addiction of Cells by Stimulating Lysosomal Exocytosis.}, journal = {Developmental cell}, volume = {55}, number = {4}, pages = {387-397.e8}, doi = {10.1016/j.devcel.2020.08.009}, pmid = {32918875}, issn = {1878-1551}, mesh = {Acids/*metabolism ; Animals ; CRISPR-Cas Systems/genetics ; Caenorhabditis elegans/metabolism ; Conserved Sequence ; Dogs ; Evolution, Molecular ; *Exocytosis ; HEK293 Cells ; Humans ; Immediate-Early Proteins/*metabolism ; Intracellular Membranes/metabolism ; Lysosomes/*metabolism ; Madin Darby Canine Kidney Cells ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Neoplasm Proteins/*metabolism ; Protein Tyrosine Phosphatases/*metabolism ; }, abstract = {Extracellular pH is usually maintained around 7.4 in multicellular organisms, and cells are optimized to proliferate under this condition. Here, we find cells can adapt to a more acidic pH of 6.5 and become addicted to this acidic microenvironment by expressing phosphatase of regenerating liver (PRL), a driver of cancer malignancy. Genome-scale CRISPR-Cas9 knockout screening and subsequent analyses revealed that PRL promotes H[+] extrusion and acid addiction by stimulating lysosomal exocytosis. Further experiments using cultured cells and Caenorhabditis elegans clarified the molecular link between PRL and lysosomal exocytosis across species, involving activation of lysosomal Ca[2+] channel TRPML by ROS. Indeed, disruption of TRPML in cancer cells abolished PRL-stimulated lysosomal exocytosis, acid addiction, and metastasis. Thus, PRL is the molecular switch turning cells addicted to an acidic condition, which should benefit cancer cells to thrive in an acidic tumor microenvironment.}, } @article {pmid32916803, year = {2020}, author = {Simões, R and Rodrigues, A and Ferreira-Dias, S and Miranda, I and Pereira, H}, title = {Chemical Composition of Cuticular Waxes and Pigments and Morphology of Leaves of Quercus suber Trees of Different Provenance.}, journal = {Plants (Basel, Switzerland)}, volume = {9}, number = {9}, pages = {}, pmid = {32916803}, issn = {2223-7747}, abstract = {The chemical composition of cuticular waxes and pigments and the morphological features of cork oak (Quercus suber) leaves were determined for six samples with seeds of different geographical origins covering the natural distribution of the species. The leaves of all samples exhibited a hard texture and oval shape with a dark green colour on the hairless adaxial surface, while the abaxial surface was lighter, with numerous stomata and densely covered with trichomes in the form of stellate multicellular hairs. The results suggest an adaptive role of leaf features among samples of different provenance and the potential role of such variability in dealing with varying temperatures and rainfall regimes through local adaptation and phenotypic plasticity, as was seen in the trial site, since no significant differences in leaf traits among the various specimens were found, for example, specific leaf area 55.6-67.8 cm[2]/g, leaf size 4.6-6.8 cm[2] and photosynthetic pigment (total chlorophyll, 31.8-40.4 µg/cm[2]). The leaves showed a substantial cuticular wax layer (154.3-235.1 µg/cm[2]) composed predominantly of triterpenes and aliphatic compounds (61-72% and 17-23% of the identified compounds, respectively) that contributed to forming a nearly impermeable membrane that helps the plant cope with drought conditions. These characteristics are related to the species and did not differ among trees of different seed origin. The major identified compound was lupeol, indicating that cork oak leaves may be considered as a potential source of this bioactive compound.}, } @article {pmid32914530, year = {2020}, author = {Gao, M and Mackley, IGP and Mesbahi-Vasey, S and Bamonte, HA and Struyvenberg, SA and Landolt, L and Pederson, NJ and Williams, LI and Bahl, CD and Brooks, L and Amacher, JF}, title = {Structural characterization and computational analysis of PDZ domains in Monosiga brevicollis.}, journal = {Protein science : a publication of the Protein Society}, volume = {29}, number = {11}, pages = {2226-2244}, pmid = {32914530}, issn = {1469-896X}, support = {S10OD021832/NH/NIH HHS/United States ; S10 OD021832/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Algorithms ; Choanoflagellata/*chemistry/genetics ; Crystallography, X-Ray ; Databases, Protein ; *Models, Molecular ; *PDZ Domains ; Protozoan Proteins/*chemistry/genetics ; *Sequence Analysis, Protein ; }, abstract = {Identification of the molecular networks that facilitated the evolution of multicellular animals from their unicellular ancestors is a fundamental problem in evolutionary cellular biology. Choanoflagellates are recognized as the closest extant nonmetazoan ancestors to animals. These unicellular eukaryotes can adopt a multicellular-like "rosette" state. Therefore, they are compelling models for the study of early multicellularity. Comparative studies revealed that a number of putative human orthologs are present in choanoflagellate genomes, suggesting that a subset of these genes were necessary for the emergence of multicellularity. However, previous work is largely based on sequence alignments alone, which does not confirm structural nor functional similarity. Here, we focus on the PDZ domain, a peptide-binding domain which plays critical roles in myriad cellular signaling networks and which underwent a gene family expansion in metazoan lineages. Using a customized sequence similarity search algorithm, we identified 178 PDZ domains in the Monosiga brevicollis proteome. This includes 11 previously unidentified sequences, which we analyzed using Rosetta and homology modeling. To assess conservation of protein structure, we solved high-resolution crystal structures of representative M. brevicollis PDZ domains that are homologous to human Dlg1 PDZ2, Dlg1 PDZ3, GIPC, and SHANK1 PDZ domains. To assess functional conservation, we calculated binding affinities for mbGIPC, mbSHANK1, mbSNX27, and mbDLG-3 PDZ domains from M. brevicollis. Overall, we find that peptide selectivity is generally conserved between these two disparate organisms, with one possible exception, mbDLG-3. Overall, our results provide novel insight into signaling pathways in a choanoflagellate model of primitive multicellularity.}, } @article {pmid32905405, year = {2020}, author = {Han, YL and Pegoraro, AF and Li, H and Li, K and Yuan, Y and Xu, G and Gu, Z and Sun, J and Hao, Y and Gupta, SK and Li, Y and Tang, W and Tang, X and Teng, L and Fredberg, JJ and Guo, M}, title = {Cell swelling, softening and invasion in a three-dimensional breast cancer model.}, journal = {Nature physics}, volume = {16}, number = {1}, pages = {101-108}, pmid = {32905405}, issn = {1745-2473}, support = {P01 HL120839/HL/NHLBI NIH HHS/United States ; R01 HL148152/HL/NHLBI NIH HHS/United States ; U01 CA202123/CA/NCI NIH HHS/United States ; }, abstract = {Sculpting of structure and function of three-dimensional multicellular tissues depend critically on the spatial and temporal coordination of cellular physical properties, yet the organizational principles that govern these events, and their disruption in disease, remain poorly understood. Using a multicellular mammary cancer organoid model, here we map in three dimensions the spatial and temporal evolution of positions, motions, and physical characteristics of individual cells. Compared with cells in the organoid core, cells at the organoid periphery and the invasive front are found to be systematically softer, larger and more dynamic. These mechanical changes are shown to arise from supracellular fluid flow through gap junctions, suppression of which delays transition to an invasive phenotype. Together, these findings highlight the role of spatiotemporal coordination of cellular physical properties in tissue organization and disease progression.}, } @article {pmid32900997, year = {2020}, author = {Fukushima, K and Pollock, DD}, title = {Amalgamated cross-species transcriptomes reveal organ-specific propensity in gene expression evolution.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4459}, pmid = {32900997}, issn = {2041-1723}, support = {R01 GM083127/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Databases, Nucleic Acid ; *Evolution, Molecular ; Female ; Gene Duplication ; Humans ; Male ; Models, Genetic ; Multigene Family ; Organ Specificity ; Phylogeny ; Proteins/genetics ; RNA-Seq ; Species Specificity ; *Transcriptome ; Vertebrates/classification/genetics ; }, abstract = {The origins of multicellular physiology are tied to evolution of gene expression. Genes can shift expression as organisms evolve, but how ancestral expression influences altered descendant expression is not well understood. To examine this, we amalgamate 1,903 RNA-seq datasets from 182 research projects, including 6 organs in 21 vertebrate species. Quality control eliminates project-specific biases, and expression shifts are reconstructed using gene-family-wise phylogenetic Ornstein-Uhlenbeck models. Expression shifts following gene duplication result in more drastic changes in expression properties than shifts without gene duplication. The expression properties are tightly coupled with protein evolutionary rate, depending on whether and how gene duplication occurred. Fluxes in expression patterns among organs are nonrandom, forming modular connections that are reshaped by gene duplication. Thus, if expression shifts, ancestral expression in some organs induces a strong propensity for expression in particular organs in descendants. Regardless of whether the shifts are adaptive or not, this supports a major role for what might be termed preadaptive pathways of gene expression evolution.}, } @article {pmid32889101, year = {2020}, author = {Sidorova, A and Tverdislov, V and Levashova, N and Garaeva, A}, title = {A model of autowave self-organization as a hierarchy of active media in the biological evolution.}, journal = {Bio Systems}, volume = {198}, number = {}, pages = {104234}, doi = {10.1016/j.biosystems.2020.104234}, pmid = {32889101}, issn = {1872-8324}, mesh = {*Algorithms ; *Biological Evolution ; Eukaryota/*classification/cytology/genetics ; *Genetic Speciation ; Genome/genetics ; *Models, Theoretical ; Mutation/genetics ; Prokaryotic Cells/*classification/metabolism ; Species Specificity ; Time Factors ; }, abstract = {Within the framework of the active media concept, we develop a biophysical model of autowave self-organization which is treated as a hierarchy of active media in the evolution of the biosphere. We also propose a mathematical model of the autowave process of speciation in a flow of mutations for the three main taxonometric groups (prokaryotes, unicellular and multicellular eukaryotes) with a naturally determined lower boundary of living matter (the appearance of prokaryotes) and an open upper boundary for the formation of new species. It is shown that the fluctuation-bifurcation description of the evolution for the formation of new taxonometric groups as a trajectory of transformation of small fluctuations into giant ones adequately reflects the process of self-organization during the formation of taxa. The major concepts of biological evolution, conditions of hierarchy formation as a fundamental manifestation of self-organization and complexity in the evolution of biological systems are considered.}, } @article {pmid32888478, year = {2020}, author = {Pentz, JT and Márquez-Zacarías, P and Bozdag, GO and Burnetti, A and Yunker, PJ and Libby, E and Ratcliff, WC}, title = {Ecological Advantages and Evolutionary Limitations of Aggregative Multicellular Development.}, journal = {Current biology : CB}, volume = {30}, number = {21}, pages = {4155-4164.e6}, doi = {10.1016/j.cub.2020.08.006}, pmid = {32888478}, issn = {1879-0445}, mesh = {*Biological Evolution ; Cell Adhesion/*physiology ; *Models, Biological ; Saccharomyces cerevisiae/*growth & development ; }, abstract = {All multicellular organisms develop through one of two basic routes: they either aggregate from free-living cells, creating potentially chimeric multicellular collectives, or they develop clonally via mother-daughter cellular adhesion. Although evolutionary theory makes clear predictions about trade-offs between these developmental modes, these have never been experimentally tested in otherwise genetically identical organisms. We engineered unicellular baker's yeast (Saccharomyces cerevisiae) to develop either clonally ("snowflake"; Δace2) or aggregatively ("floc"; GAL1p::FLO1) and examined their fitness in a fluctuating environment characterized by periods of growth and selection for rapid sedimentation. When cultured independently, aggregation was far superior to clonal development, providing a 35% advantage during growth and a 2.5-fold advantage during settling selection. Yet when competed directly, clonally developing snowflake yeast rapidly displaced aggregative floc. This was due to unexpected social exploitation: snowflake yeast, which do not produce adhesive FLO1, nonetheless become incorporated into flocs at a higher frequency than floc cells themselves. Populations of chimeric clusters settle much faster than floc alone, providing snowflake yeast with a fitness advantage during competition. Mathematical modeling suggests that such developmental cheating may be difficult to circumvent; hypothetical "choosy floc" that avoid exploitation by maintaining clonality pay an ecological cost when rare, often leading to their extinction. Our results highlight the conflict at the heart of aggregative development: non-specific cellular binding provides a strong ecological advantage-the ability to quickly form groups-but this very feature leads to its exploitation.}, } @article {pmid32882615, year = {2020}, author = {Ruiz-Arrebola, S and Tornero-López, AM and Guirado, D and Villalobos, M and Lallena, AM}, title = {An on-lattice agent-based Monte Carlo model simulating the growth kinetics of multicellular tumor spheroids.}, journal = {Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)}, volume = {77}, number = {}, pages = {194-203}, doi = {10.1016/j.ejmp.2020.07.026}, pmid = {32882615}, issn = {1724-191X}, mesh = {*Breast Neoplasms ; Female ; Humans ; Kinetics ; Monte Carlo Method ; Necrosis ; *Spheroids, Cellular ; }, abstract = {PURPOSE: To develop an on-lattice agent-based model describing the growth of multicellular tumor spheroids using simple Monte Carlo tools.

METHODS: Cells are situated on the vertices of a cubic grid. Different cell states (proliferative, hypoxic or dead) and cell evolution rules, driven by 10 parameters, and the effects of the culture medium are included. About twenty spheroids of MCF-7 human breast cancer were cultivated and the experimental data were used for tuning the model parameters.

RESULTS: Simulated spheroids showed adequate sizes of the necrotic nuclei and of the hypoxic and proliferative cell phases as a function of the growth time, mimicking the overall characteristics of the experimental spheroids. The relation between the radii of the necrotic nucleus and the whole spheroid obtained in the simulations was similar to the experimental one and the number of cells, as a function of the spheroid volume, was well reproduced. The statistical variability of the Monte Carlo model described the whole volume range observed for the experimental spheroids. Assuming that the model parameters vary within Gaussian distributions it was obtained a sample of spheroids that reproduced much better the experimental findings.

CONCLUSIONS: The model developed allows describing the growth of in vitro multicellular spheroids and the experimental variability can be well reproduced. Its flexibility permits to vary both the agents involved and the rules that govern the spheroid growth. More general situations, such as, e. g., tumor vascularization, radiotherapy effects on solid tumors, or the validity of the tumor growth mathematical models can be studied.}, } @article {pmid32873627, year = {2021}, author = {Saucedo, LJ and Triolo, RE and Segar, KE}, title = {How Drosophila Can Inform the Emerging Paradigm of the Role of Antioxidants in Cancer.}, journal = {Molecular cancer research : MCR}, volume = {19}, number = {1}, pages = {38-41}, doi = {10.1158/1541-7786.MCR-20-0172}, pmid = {32873627}, issn = {1557-3125}, mesh = {Animals ; Antioxidants/*metabolism ; Drosophila melanogaster/*genetics ; Humans ; Neoplasms/*genetics ; }, abstract = {Drosophila melanogaster has proven to be an effective model system in uncovering both genetic and cellular contributions to human cancer. Many elusive genes and signaling pathways that control oncogenic growth were first identified using flies. In many cases, these discoveries were not driven by a direct search for novel genes involved in cancer but rather stemmed from research programs to uncover mechanisms that control growth and development. However, the bounty of genetic tools and the shared evolution of multicellular organisms places Drosophila in a powerful position to purposefully elucidate observations seen in human cancers. In the past decade, the role of antioxidants in cancer progression has shifted dramatically. This review highlights major findings driving this change in perspective and underscores an array of existing work and resources in laboratories using Drosophila that can make significant contributions to how the redox environment affects cancer progression.}, } @article {pmid32871001, year = {2021}, author = {Futo, M and Opašić, L and Koska, S and Čorak, N and Široki, T and Ravikumar, V and Thorsell, A and Lenuzzi, M and Kifer, D and Domazet-Lošo, M and Vlahoviček, K and Mijakovic, I and Domazet-Lošo, T}, title = {Embryo-Like Features in Developing Bacillus subtilis Biofilms.}, journal = {Molecular biology and evolution}, volume = {38}, number = {1}, pages = {31-47}, pmid = {32871001}, issn = {1537-1719}, mesh = {Bacillus subtilis/cytology/*physiology ; *Biofilms ; *Biological Evolution ; }, abstract = {Correspondence between evolution and development has been discussed for more than two centuries. Recent work reveals that phylogeny-ontogeny correlations are indeed present in developmental transcriptomes of eukaryotic clades with complex multicellularity. Nevertheless, it has been largely ignored that the pervasive presence of phylogeny-ontogeny correlations is a hallmark of development in eukaryotes. This perspective opens a possibility to look for similar parallelisms in biological settings where developmental logic and multicellular complexity are more obscure. For instance, it has been increasingly recognized that multicellular behavior underlies biofilm formation in bacteria. However, it remains unclear whether bacterial biofilm growth shares some basic principles with development in complex eukaryotes. Here we show that the ontogeny of growing Bacillus subtilis biofilms recapitulates phylogeny at the expression level. Using time-resolved transcriptome and proteome profiles, we found that biofilm ontogeny correlates with the evolutionary measures, in a way that evolutionary younger and more diverged genes were increasingly expressed toward later timepoints of biofilm growth. Molecular and morphological signatures also revealed that biofilm growth is highly regulated and organized into discrete ontogenetic stages, analogous to those of eukaryotic embryos. Together, this suggests that biofilm formation in Bacillus is a bona fide developmental process comparable to organismal development in animals, plants, and fungi. Given that most cells on Earth reside in the form of biofilms and that biofilms represent the oldest known fossils, we anticipate that the widely adopted vision of the first life as a single-cell and free-living organism needs rethinking.}, } @article {pmid32861802, year = {2020}, author = {Stewart, JE}, title = {Towards a general theory of the major cooperative evolutionary transitions.}, journal = {Bio Systems}, volume = {198}, number = {}, pages = {104237}, doi = {10.1016/j.biosystems.2020.104237}, pmid = {32861802}, issn = {1872-8324}, mesh = {Adaptation, Physiological/*physiology ; *Biological Evolution ; *Communication ; *Cooperative Behavior ; Humans ; Political Systems ; Public Policy ; Social Behavior ; Socioeconomic Factors ; }, abstract = {Major Cooperative Evolutionary Transitions occur when smaller-scale entities cooperate together to give rise to larger-scale entities that evolve and adapt as coherent wholes. Key examples of cooperative transitions are the emergence of the complex eukaryote cell from communities of simpler cells, the transition from eukaryote cells to multicellular organisms, and the organization of humans into complex, modern societies. A number of attempts have been made to develop a general theory of the major cooperative transitions. This paper begins by critiquing key aspects of these previous attempts. Largely, these attempts comprise poorly-integrated collections of separate models that were each originally developed to explain particular transitions. In contrast, this paper sets out to identify processes that are common to all cooperative transitions. It develops an alternative theoretical framework known as Management Theory. This general framework suggests that all major cooperative transitions are the result of the emergence of powerful, evolvable 'managers' that derive benefit from using their power to organize smaller-scale entities into larger-scale cooperatives. Management Theory is a contribution to the development of a general, "all levels" understanding of major cooperative transitions that is capable of identifying those features that are level-specific, those that are common across levels and those that are involved in trends across levels.}, } @article {pmid32857975, year = {2020}, author = {Parra-Acero, H and Harcet, M and Sánchez-Pons, N and Casacuberta, E and Brown, NH and Dudin, O and Ruiz-Trillo, I}, title = {Integrin-Mediated Adhesion in the Unicellular Holozoan Capsaspora owczarzaki.}, journal = {Current biology : CB}, volume = {30}, number = {21}, pages = {4270-4275.e4}, doi = {10.1016/j.cub.2020.08.015}, pmid = {32857975}, issn = {1879-0445}, mesh = {CD18 Antigens/metabolism ; Cell Adhesion/*physiology ; Eukaryota/cytology/*physiology ; Fibronectins/metabolism ; Integrins/metabolism ; Pseudopodia/metabolism ; Vinculin/metabolism ; }, abstract = {In animals, cell-matrix adhesions are essential for cell migration, tissue organization, and differentiation, which have central roles in embryonic development [1-6]. Integrins are the major cell surface adhesion receptors mediating cell-matrix adhesion in animals. They are heterodimeric transmembrane proteins that bind extracellular matrix (ECM) molecules on one side and connect to the actin cytoskeleton on the other [7]. Given the importance of integrin-mediated cell-matrix adhesion in development of multicellular animals, it is of interest to discover when and how this machinery arose during evolution. Comparative genomic analyses have shown that core components of the integrin adhesome pre-date the emergence of animals [8-11]; however, whether it mediates cell adhesion in non-metazoan taxa remains unknown. Here, we investigate cell-substrate adhesion in Capsaspora owczarzaki, the closest unicellular relative of animals with the most complete integrin adhesome [11, 12]. Previous work described that the life cycle of C. owczarzaki (hereafter, Capsaspora) includes three distinct life stages: adherent; cystic; and aggregative [13]. Using an adhesion assay, we show that, during the adherent life stage, C. owczarzaki adheres to surfaces using actin-dependent filopodia. We show that integrin β2 and its associated protein vinculin localize as distinct patches in the filopodia. We also demonstrate that substrate adhesion and integrin localization are enhanced by mammalian fibronectin. Finally, using a specific antibody for integrin β2, we inhibited cell adhesion to a fibronectin-coated surface. Our results suggest that adhesion to the substrate in C. owczarzaki is mediated by integrins. We thus propose that integrin-mediated adhesion pre-dates the emergence of animals.}, } @article {pmid32855242, year = {2020}, author = {Zhang, W and Ji, R and Liu, J and Pan, Y and Wu, LF and Lin, W}, title = {Two Metagenome-Assembled Genome Sequences of Magnetotactic Bacteria in the Order Magnetococcales.}, journal = {Microbiology resource announcements}, volume = {9}, number = {35}, pages = {}, pmid = {32855242}, issn = {2576-098X}, abstract = {Magnetotactic bacteria represent a valuable model system for the study of microbial biomineralization and magnetotaxis. Here, we report two metagenome-assembled genome sequences of uncultivated magnetotactic bacteria belonging to the order Magnetococcales These genomes contain nearly complete magnetosome gene clusters responsible for magnetosome biomineralization.}, } @article {pmid32849605, year = {2020}, author = {Pérez-Hernández, CA and Kern, CC and Butkeviciute, E and McCarthy, E and Dockrell, HM and Moreno-Altamirano, MMB and Aguilar-López, BA and Bhosale, G and Wang, H and Gems, D and Duchen, MR and Smith, SG and Sánchez-García, FJ}, title = {Mitochondrial Signature in Human Monocytes and Resistance to Infection in C. elegans During Fumarate-Induced Innate Immune Training.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1715}, pmid = {32849605}, issn = {1664-3224}, support = {MR/R005850/1/MRC_/Medical Research Council/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 098565/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; 215574/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Caenorhabditis elegans/*drug effects/immunology/metabolism/microbiology ; Calcium Signaling/drug effects ; Cells, Cultured ; Cytokines/metabolism ; Escherichia coli/immunology/*pathogenicity ; Escherichia coli Infections/immunology/metabolism/microbiology/*prevention & control ; Fumarates/*pharmacology ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/*drug effects ; Immunologic Memory/*drug effects ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/*drug effects/immunology/metabolism ; Mitochondrial Dynamics/drug effects ; Monocytes/*drug effects/immunology/metabolism ; }, abstract = {Monocytes can develop immunological memory, a functional characteristic widely recognized as innate immune training, to distinguish it from memory in adaptive immune cells. Upon a secondary immune challenge, either homologous or heterologous, trained monocytes/macrophages exhibit a more robust production of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, than untrained monocytes. Candida albicans, β-glucan, and BCG are all inducers of monocyte training and recent metabolic profiling analyses have revealed that training induction is dependent on glycolysis, glutaminolysis, and the cholesterol synthesis pathway, along with fumarate accumulation; interestingly, fumarate itself can induce training. Since fumarate is produced by the tricarboxylic acid (TCA) cycle within mitochondria, we asked whether extra-mitochondrial fumarate has an effect on mitochondrial function. Results showed that the addition of fumarate to monocytes induces mitochondrial Ca[2+] uptake, fusion, and increased membrane potential (Δψm), while mitochondrial cristae became closer to each other, suggesting that immediate (from minutes to hours) mitochondrial activation plays a role in the induction phase of innate immune training of monocytes. To establish whether fumarate induces similar mitochondrial changes in vivo in a multicellular organism, effects of fumarate supplementation were tested in the nematode worm Caenorhabditis elegans. This induced mitochondrial fusion in both muscle and intestinal cells and also increased resistance to infection of the pharynx with E. coli. Together, these findings contribute to defining a mitochondrial signature associated with the induction of innate immune training by fumarate treatment, and to the understanding of whole organism infection resistance.}, } @article {pmid32839450, year = {2020}, author = {Du, P and Zhao, H and Zhang, H and Wang, R and Huang, J and Tian, Y and Luo, X and Luo, X and Wang, M and Xiang, Y and Qian, L and Chen, Y and Tao, Y and Lou, C}, title = {De novo design of an intercellular signaling toolbox for multi-channel cell-cell communication and biological computation.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4226}, pmid = {32839450}, issn = {2041-1723}, mesh = {Cell Communication/*genetics ; Computational Biology/*methods ; Escherichia coli/genetics/metabolism ; Green Fluorescent Proteins/genetics/metabolism ; HEK293 Cells ; Humans ; Microscopy, Fluorescence ; Mutation ; Reproducibility of Results ; Saccharomyces cerevisiae/genetics/metabolism ; Signal Transduction/*genetics ; Transcription Factors/*genetics/metabolism ; }, abstract = {Intercellular signaling is indispensable for single cells to form complex biological structures, such as biofilms, tissues and organs. The genetic tools available for engineering intercellular signaling, however, are quite limited. Here we exploit the chemical diversity of biological small molecules to de novo design a genetic toolbox for high-performance, multi-channel cell-cell communications and biological computations. By biosynthetic pathway design for signal molecules, rational engineering of sensing promoters and directed evolution of sensing transcription factors, we obtain six cell-cell signaling channels in bacteria with orthogonality far exceeding the conventional quorum sensing systems and successfully transfer some of them into yeast and human cells. For demonstration, they are applied in cell consortia to generate bacterial colony-patterns using up to four signaling channels simultaneously and to implement distributed bio-computation containing seven different strains as basic units. This intercellular signaling toolbox paves the way for engineering complex multicellularity including artificial ecosystems and smart tissues.}, } @article {pmid32829916, year = {2021}, author = {Márquez-Zacarías, P and Pineau, RM and Gomez, M and Veliz-Cuba, A and Murrugarra, D and Ratcliff, WC and Niklas, KJ}, title = {Evolution of Cellular Differentiation: From Hypotheses to Models.}, journal = {Trends in ecology & evolution}, volume = {36}, number = {1}, pages = {49-60}, doi = {10.1016/j.tree.2020.07.013}, pmid = {32829916}, issn = {1872-8383}, mesh = {*Biological Evolution ; Cell Differentiation ; }, abstract = {Cellular differentiation is one of the hallmarks of complex multicellularity, allowing individual organisms to capitalize on among-cell functional diversity. The evolution of multicellularity is a major evolutionary transition that allowed for the increase of organismal complexity in multiple lineages, a process that relies on the functional integration of cell-types within an individual. Multiple hypotheses have been proposed to explain the origins of cellular differentiation, but we lack a general understanding of what makes one cell-type distinct from others, and how such differentiation arises. Here, we describe how the use of Boolean networks (BNs) can aid in placing empirical findings into a coherent conceptual framework, and we emphasize some of the standing problems when interpreting data and model behaviors.}, } @article {pmid32822576, year = {2020}, author = {Maynard, A and McCoach, CE and Rotow, JK and Harris, L and Haderk, F and Kerr, DL and Yu, EA and Schenk, EL and Tan, W and Zee, A and Tan, M and Gui, P and Lea, T and Wu, W and Urisman, A and Jones, K and Sit, R and Kolli, PK and Seeley, E and Gesthalter, Y and Le, DD and Yamauchi, KA and Naeger, DM and Bandyopadhyay, S and Shah, K and Cech, L and Thomas, NJ and Gupta, A and Gonzalez, M and Do, H and Tan, L and Bacaltos, B and Gomez-Sjoberg, R and Gubens, M and Jahan, T and Kratz, JR and Jablons, D and Neff, N and Doebele, RC and Weissman, J and Blakely, CM and Darmanis, S and Bivona, TG}, title = {Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing.}, journal = {Cell}, volume = {182}, number = {5}, pages = {1232-1251.e22}, pmid = {32822576}, issn = {1097-4172}, support = {R01 CA227807/CA/NCI NIH HHS/United States ; T32 HL007185/HL/NHLBI NIH HHS/United States ; U54 CA224081/CA/NCI NIH HHS/United States ; R01 CA211052/CA/NCI NIH HHS/United States ; U01 CA217882/CA/NCI NIH HHS/United States ; 2018110/DDCF_/Doris Duke Charitable Foundation/United States ; R01 CA231300/CA/NCI NIH HHS/United States ; R01 CA169338/CA/NCI NIH HHS/United States ; R01 CA204302/CA/NCI NIH HHS/United States ; K12 CA086913/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics ; Cell Line ; Ecosystem ; Humans ; Lung Neoplasms/*genetics/pathology ; Macrophages/pathology ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; T-Lymphocytes/pathology ; Tumor Microenvironment/genetics ; }, abstract = {Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) of metastatic lung cancer was performed using 49 clinical biopsies obtained from 30 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNA-seq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell-state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap-junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNA-seq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.}, } @article {pmid32821912, year = {2020}, author = {Ramisetty, BCM and Sudhakari, PA}, title = {'Bacterial Programmed Cell Death': cellular altruism or genetic selfism?.}, journal = {FEMS microbiology letters}, volume = {367}, number = {16}, pages = {}, doi = {10.1093/femsle/fnaa141}, pmid = {32821912}, issn = {1574-6968}, mesh = {Apoptosis/*physiology ; Bacteria/cytology/genetics ; *Bacterial Physiological Phenomena/genetics ; Biological Evolution ; Genes, Bacterial/genetics ; }, abstract = {Cell-dependent propagation of the 'self' is the driver of all species, organisms and even genes. Conceivably, elimination of these entities is caused by cellular death. Then, how can genes that cause the death of the same cell evolve? Programmed cell death (PCD) is the gene-dependent self-inflicted death. In multicellular organisms, PCD of a cell confers fitness to the surviving rest of the organism, which thereby allows the selection of genes responsible for PCD. However, PCD in free-living bacteria is intriguing; the death of the cell is the death of the organism. How can such PCD genes be selected in unicellular organisms? The bacterial PCD in a population is proposed to confer fitness to the surviving kin in the form of sporulation, nutrition, infection-containment and matrix materials. While the cell-centred view leading to propositions of 'altruism' is enticing, the gene-centred view of 'selfism' is neglected. In this opinion piece, we reconceptualize the PCD propositions as genetic selfism (death due to loss/mutation of selfish genes) rather than cellular altruism (death for the conferment of fitness to kin). Within the scope and the available evidence, we opine that some of the PCD-like observations in bacteria seem to be the manifestation of genetic selfism by Restriction-Modification systems and Toxin-Antitoxin systems.}, } @article {pmid32821904, year = {2020}, author = {Chen, H and Li, D and Cai, Y and Wu, LF and Song, T}, title = {Bacteriophytochrome from Magnetospirillum magneticum affects phototactic behavior in response to light.}, journal = {FEMS microbiology letters}, volume = {367}, number = {17}, pages = {}, doi = {10.1093/femsle/fnaa142}, pmid = {32821904}, issn = {1574-6968}, mesh = {*Light ; Magnetospirillum/*genetics/*radiation effects ; Mutagenesis, Site-Directed ; Phototaxis/*physiology ; Phytochrome/*genetics ; }, abstract = {Phytochromes are a class of photoreceptors found in plants and in some fungi, cyanobacteria, and photoautotrophic and heterotrophic bacteria. Although phytochromes have been structurally characterized in some bacteria, their biological and ecological roles in magnetotactic bacteria remain unexplored. Here, we describe the biochemical characterization of recombinant bacteriophytochrome (BphP) from magnetotactic bacteria Magnetospirillum magneticum AMB-1 (MmBphP). The recombinant MmBphP displays all the characteristic features, including the property of binding to biliverdin (BV), of a genuine phytochrome. Site-directed mutagenesis identified that cysteine-14 is important for chromophore covalent binding and photoreversibility. Arginine-240 and histidine-246 play key roles in binding to BV. The N-terminal photosensory core domain of MmBphP lacking the C-terminus found in other phytochromes is sufficient to exhibit the characteristic red/far-red-light-induced fast photoreversibility of phytochromes. Moreover, our results showed MmBphP is involved in the phototactic response, suggesting its conservative role as a stress protectant. This finding provided us a better understanding of the physiological function of this group of photoreceptors and photoresponse of magnetotactic bacteria.}, } @article {pmid32821281, year = {2020}, author = {Birtwell, D and Luebeck, G and Maley, CC}, title = {The evolution of metapopulation dynamics and the number of stem cells in intestinal crypts and other tissue structures in multicellular bodies.}, journal = {Evolutionary applications}, volume = {13}, number = {7}, pages = {1771-1783}, pmid = {32821281}, issn = {1752-4571}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; P30 CA010815/CA/NCI NIH HHS/United States ; U01 CA182940/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R03 CA137811/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; R01 CA119224/CA/NCI NIH HHS/United States ; }, abstract = {Carcinogenesis is a process of somatic evolution. Previous models of stem and transient amplifying cells in epithelial proliferating units like colonic crypts showed that intermediate numbers of stem cells in a crypt should optimally prevent progression to cancer. If a stem cell population is too small, it is easy for a mutator mutation to drift to fixation. If it is too large, it is easy for selection to drive cell fitness enhancing carcinogenic mutations to fixation. Here, we show that a multiscale microsimulation, that captures both within-crypt and between-crypt evolutionary dynamics, leads to a different conclusion. Epithelial tissues are metapopulations of crypts. We measured time to initiation of a neoplasm, implemented as inactivation of both alleles of a tumor suppressor gene. In our model, time to initiation is dependent on the spread of mutator clones in the crypts. The proportion of selectively beneficial and deleterious mutations in somatic cells is unknown and so was explored with a parameter. When the majority of non-neutral mutations are deleterious, the fitness of mutator clones tends to decline. When crypts are maintained by few stem cells, intercrypt competition tends to remove crypts with fixed mutators. When there are many stem cells within a crypt, there is virtually no crypt turnover, but mutator clones are suppressed by within-crypt competition. If the majority of non-neutral mutations are beneficial to the clone, then these results are reversed and intermediate-sized crypts provide the most protection against initiation. These results highlight the need to understand the dynamics of turnover and the mechanisms that control homeostasis, both at the level of stem cells within proliferative units and at the tissue level of competing proliferative units. Determining the distribution of fitness effects of somatic mutations will also be crucial to understanding the dynamics of tumor initiation and progression.}, } @article {pmid32810421, year = {2020}, author = {Grassam-Rowe, A and Ou, X and Lei, M}, title = {Novel cardiac cell subpopulations: Pnmt-derived cardiomyocytes.}, journal = {Open biology}, volume = {10}, number = {8}, pages = {200095}, pmid = {32810421}, issn = {2046-2441}, support = {G1002082/MRC_/Medical Research Council/United Kingdom ; PG/14/80/31106/BHF_/British Heart Foundation/United Kingdom ; G10002647/MRC_/Medical Research Council/United Kingdom ; G1002647/MRC_/Medical Research Council/United Kingdom ; PG/11/59/29004/BHF_/British Heart Foundation/United Kingdom ; PG/16/67/32340/BHF_/British Heart Foundation/United Kingdom ; PG/12/21/29473/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Age Factors ; Animals ; Biomarkers ; Catecholamines/metabolism ; *Cell Plasticity ; Electrophysiological Phenomena ; Humans ; Myocardium/cytology/enzymology/metabolism ; Myocytes, Cardiac/*cytology/*metabolism ; Organogenesis/genetics ; Phenotype ; Phenylethanolamine N-Methyltransferase/genetics/*metabolism ; }, abstract = {Diversity among highly specialized cells underlies the fundamental biology of complex multi-cellular organisms. One of the essential scientific questions in cardiac biology has been to define subpopulations within the heart. The heart parenchyma comprises specialized cardiomyocytes (CMs). CMs have been canonically classified into a few phenotypically diverse subpopulations largely based on their function and anatomic localization. However, there is growing evidence that CM subpopulations are in fact numerous, with a diversity of genetic origin and putatively different roles in physiology and pathophysiology. In this chapter, we introduce a recently discovered CM subpopulation: phenylethanolamine-N-methyl transferase (Pnmt)-derived cardiomyocytes (PdCMs). We discuss: (i) canonical classifications of CM subpopulations; (ii) discovery of PdCMs; (iii) Pnmt and the role of catecholamines in the heart; similarities and dissimilarities of PdCMs and canonical CMs; and (iv) putative functions of PdCMs in both physiological and pathological states and future directions, such as in intra-cardiac adrenergic signalling.}, } @article {pmid32797190, year = {2021}, author = {Ho, AT and Hurst, LD}, title = {Effective Population Size Predicts Local Rates but Not Local Mitigation of Read-through Errors.}, journal = {Molecular biology and evolution}, volume = {38}, number = {1}, pages = {244-262}, pmid = {32797190}, issn = {1537-1719}, mesh = {Arabidopsis ; *Codon, Terminator ; Dictyostelium ; *Evolution, Molecular ; *Mutation Rate ; Population Density ; *Selection, Genetic ; }, abstract = {In correctly predicting that selection efficiency is positively correlated with the effective population size (Ne), the nearly neutral theory provides a coherent understanding of between-species variation in numerous genomic parameters, including heritable error (germline mutation) rates. Does the same theory also explain variation in phenotypic error rates and in abundance of error mitigation mechanisms? Translational read-through provides a model to investigate both issues as it is common, mostly nonadaptive, and has good proxy for rate (TAA being the least leaky stop codon) and potential error mitigation via "fail-safe" 3' additional stop codons (ASCs). Prior theory of translational read-through has suggested that when population sizes are high, weak selection for local mitigation can be effective thus predicting a positive correlation between ASC enrichment and Ne. Contra to prediction, we find that ASC enrichment is not correlated with Ne. ASC enrichment, although highly phylogenetically patchy, is, however, more common both in unicellular species and in genes expressed in unicellular modes in multicellular species. By contrast, Ne does positively correlate with TAA enrichment. These results imply that local phenotypic error rates, not local mitigation rates, are consistent with a drift barrier/nearly neutral model.}, } @article {pmid32786305, year = {2020}, author = {Sarkar, P and Rao, BD and Chattopadhyay, A}, title = {Cell Cycle Dependent Modulation of Membrane Dipole Potential and Neurotransmitter Receptor Activity: Role of Membrane Cholesterol.}, journal = {ACS chemical neuroscience}, volume = {11}, number = {18}, pages = {2890-2899}, doi = {10.1021/acschemneuro.0c00499}, pmid = {32786305}, issn = {1948-7193}, mesh = {Cell Cycle ; Cell Membrane ; *Cholesterol ; Membrane Potentials ; *Pyridinium Compounds ; Receptors, Neurotransmitter ; }, abstract = {The cell cycle is a sequential multistep process essential for growth and proliferation of cells that make up multicellular organisms. A number of nuclear and cytoplasmic proteins are known to modulate the cell cycle. Yet, the role of lipids, membrane organization, and physical properties in cell cycle progression remains largely elusive. Membrane dipole potential is an important physicochemical property and originates due to the electrostatic potential difference within the membrane because of nonrandom arrangement of amphiphile dipoles and water molecules at the membrane interface. In this work, we explored the modulation of membrane dipole potential in various stages of the cell cycle in CHO-K1 cells. Our results show that membrane dipole potential is highest in the G1 phase relative to S and G2/M phases. This was accompanied by regulation of membrane cholesterol content in the cell cycle. The highest cholesterol content was found in the G1 phase with a considerable reduction in cholesterol in S and G2/M phases. Interestingly, we noted a similarity in the dependence of membrane dipole potential and cholesterol with progress of the cell cycle. In addition, we observed an increase in neutral lipid (which contains esterified cholesterol) content as cells progressed from the G1 to G2/M phase via the S phase of the cell cycle. Importantly, we further observed a cell cycle dependent reduction in ligand binding activity of serotonin1A receptors expressed in CHO-K1 cells. To the best of our knowledge, these results constitute the first report of cell cycle dependent modulation of membrane dipole potential and activity of a neurotransmitter receptor belonging to the G protein-coupled receptor family. We envision that understanding the basis of cell cycle events from a biophysical perspective would result in a deeper appreciation of the cell cycle and its regulation in relation to cellular function.}, } @article {pmid32780289, year = {2020}, author = {Chen, H and Li, K and Cai, Y and Wang, P and Gong, W and Wu, LF and Song, T}, title = {Light regulation of resistance to oxidative damage and magnetic crystal biogenesis in Magnetospirillum magneticum mediated by a Cys-less LOV-like protein.}, journal = {Applied microbiology and biotechnology}, volume = {104}, number = {18}, pages = {7927-7941}, doi = {10.1007/s00253-020-10807-5}, pmid = {32780289}, issn = {1432-0614}, support = {51937011//the State Key Program of National Natural Science of China/ ; Y650141CSA//the Research Project Funded by the Institute of Electrical Engineering, Chinese Academy of Sciences/ ; }, mesh = {Bacterial Proteins/genetics/metabolism ; *Cysteine/metabolism ; Magnetic Phenomena ; *Magnetospirillum/genetics/metabolism ; Oxidative Stress ; Oxygen ; }, abstract = {Light-oxygen-voltage (LOV) proteins are ubiquitous photoreceptors that can interact with other regulatory proteins and then mediate their activities, which results in cellular adaptation and subsequent physiological changes. Upon blue-light irradiation, a conserved cysteine (Cys) residue in LOV covalently binds to flavin to form a flavin-Cys adduct, which triggers a subsequent cascade of signal transduction and reactions. We found a group of natural Cys-less LOV-like proteins in magnetotactic bacteria (MTB) and investigated its physiological functions by conducting research on one of these unusual LOV-like proteins, Amb2291, in Magnetospirillum magneticum. In-frame deletion of amb2291 or site-directive substitution of alanine-399 for Cys mutants impaired the protective responses against hydrogen peroxide, thereby causing stress and growth impairment. Consequently, gene expression and magnetosome formation were affected, which led to high sensitivity to oxidative damage and defective phototactic behaviour. The purified wild-type and A399C-mutated LOV-like proteins had similar LOV blue-light response spectra, but Amb2291[A399C] exhibited a faster reaction to blue light. We especially showed that LOV-like protein Amb2291 plays a role in magnetosome synthesis and resistance to oxidative stress of AMB-1 when this bacterium was exposed to red light and hydrogen peroxide. This finding expands our knowledge of the physiological function of this widely distributed group of photoreceptors and deepens our understanding of the photoresponse of MTB. KEY POINTS: • We found a group of Cys-less light-oxygen-voltage (LOV) photoreceptors in magnetotactic bacteria, which prompted us to study the light-response and biological roles of these proteins in these non-photosynthetic bacteria. • The Cys-less LOV-like protein participates in the light-regulated signalling pathway and improves resistance to oxidative damage and magnetic crystal biogenesis in Magnetospirillum magneticum. • This result will contribute to our understanding of the structural and functional diversity of the LOV-like photoreceptor and help us understand the complexity of light-regulated model organisms.}, } @article {pmid32778581, year = {2020}, author = {Xin, Y and Le Poul, Y and Ling, L and Museridze, M and Mühling, B and Jaenichen, R and Osipova, E and Gompel, N}, title = {Enhancer evolutionary co-option through shared chromatin accessibility input.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {34}, pages = {20636-20644}, pmid = {32778581}, issn = {1091-6490}, mesh = {Animals ; Biological Evolution ; Chromatin/genetics/metabolism ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/genetics ; Enhancer Elements, Genetic/*genetics ; Evolution, Molecular ; Gene Expression Regulation, Developmental/*genetics ; Regulatory Elements, Transcriptional/genetics ; Wings, Animal/metabolism ; }, abstract = {The diversity of forms in multicellular organisms originates largely from the spatial redeployment of developmental genes [S. B. Carroll, Cell 134, 25-36 (2008)]. Several scenarios can explain the emergence of cis-regulatory elements that govern novel aspects of a gene expression pattern [M. Rebeiz, M. Tsiantis, Curr. Opin. Genet. Dev. 45, 115-123 (2017)]. One scenario, enhancer co-option, holds that a DNA sequence producing an ancestral regulatory activity also becomes the template for a new regulatory activity, sharing regulatory information. While enhancer co-option might fuel morphological diversification, it has rarely been documented [W. J. Glassford et al., Dev. Cell 34, 520-531 (2015)]. Moreover, if two regulatory activities are borne from the same sequence, their modularity, considered a defining feature of enhancers [J. Banerji, L. Olson, W. Schaffner, Cell 33, 729-740 (1983)], might be affected by pleiotropy. Sequence overlap may thereby play a determinant role in enhancer function and evolution. Here, we investigated this problem with two regulatory activities of the Drosophila gene yellow, the novel spot enhancer and the ancestral wing blade enhancer. We used precise and comprehensive quantification of each activity in Drosophila wings to systematically map their sequences along the locus. We show that the spot enhancer has co-opted the sequences of the wing blade enhancer. We also identified a pleiotropic site necessary for DNA accessibility of a shared regulatory region. While the evolutionary steps leading to the derived activity are still unknown, such pleiotropy suggests that enhancer accessibility could be one of the molecular mechanisms seeding evolutionary co-option.}, } @article {pmid32767819, year = {2020}, author = {Kundu, R}, title = {Cationic Amphiphilic Peptides: Synthetic Antimicrobial Agents Inspired by Nature.}, journal = {ChemMedChem}, volume = {15}, number = {20}, pages = {1887-1896}, doi = {10.1002/cmdc.202000301}, pmid = {32767819}, issn = {1860-7187}, mesh = {Amino Acid Sequence ; Anti-Bacterial Agents/chemistry/*pharmacology/therapeutic use ; Antimicrobial Cationic Peptides/chemistry/*pharmacology/therapeutic use ; Bacteria/drug effects ; Clinical Trials as Topic ; Humans ; Lipopeptides/chemistry/pharmacology/therapeutic use ; Peptides, Cyclic/chemistry/pharmacology/therapeutic use ; Peptidomimetics/chemistry/pharmacology/therapeutic use ; Protein Conformation, alpha-Helical ; }, abstract = {Antimicrobial peptides are ubiquitous in multicellular organisms and have served as defense mechanisms for their successful evolution and throughout their life cycle. These peptides are short cationic amphiphilic polypeptides of fewer than 50 amino acids containing either a few disulfide-linked cysteine residues with a characteristic β-sheet-rich structure or linear α-helical conformations with hydrophilic side chains at one side of the helix and hydrophobic side chains on the other side. Antimicrobial peptides cause bacterial cell lysis either by direct cell-surface damage via electrostatic interactions between the cationic side chains of the peptide and the negatively charged cell surface, or by indirect modulation of the host defense systems. Electrostatic interactions lead to bacterial cell membrane disruption followed by leakage of cellular components and finally bacterial cell death. Because of their unusual mechanism of cell damage, antimicrobial peptides are effective against drug-resistant bacteria and may therefore prove more effective than classical antibiotics in certain cases. Currently, around 3000 natural antimicrobial peptides from six kingdoms (bacteria, archaea, protists, fungi, plants, and animals) have been isolated and sequenced. However, only a few of them are under clinical trials and/or in the commercial development stage for the treatment of bacterial infections caused by antibiotic-resistant bacteria. Moreover, high structural complexity, poor pharmacokinetic properties, and low antibacterial activity of natural antimicrobial peptides hinder their progress in drug development. To overcome these hurdles, researchers have become increasingly interested in modification and nature-inspired synthetic antimicrobial peptides. This review discusses some of the recent studies reported on antimicrobial peptides.}, } @article {pmid32765213, year = {2020}, author = {Oltmanns, S and Abben, FS and Ender, A and Aimon, S and Kovacs, R and Sigrist, SJ and Storace, DA and Geiger, JRP and Raccuglia, D}, title = {NOSA, an Analytical Toolbox for Multicellular Optical Electrophysiology.}, journal = {Frontiers in neuroscience}, volume = {14}, number = {}, pages = {712}, pmid = {32765213}, issn = {1662-4548}, abstract = {Understanding how neural networks generate activity patterns and communicate with each other requires monitoring the electrical activity from many neurons simultaneously. Perfectly suited tools for addressing this challenge are genetically encoded voltage indicators (GEVIs) because they can be targeted to specific cell types and optically report the electrical activity of individual, or populations of neurons. However, analyzing and interpreting the data from voltage imaging experiments is challenging because high recording speeds and properties of current GEVIs yield only low signal-to-noise ratios, making it necessary to apply specific analytical tools. Here, we present NOSA (Neuro-Optical Signal Analysis), a novel open source software designed for analyzing voltage imaging data and identifying temporal interactions between electrical activity patterns of different origin. In this work, we explain the challenges that arise during voltage imaging experiments and provide hands-on analytical solutions. We demonstrate how NOSA's baseline fitting, filtering algorithms and movement correction can compensate for shifts in baseline fluorescence and extract electrical patterns from low signal-to-noise recordings. NOSA allows to efficiently identify oscillatory frequencies in electrical patterns, quantify neuronal response parameters and moreover provides an option for analyzing simultaneously recorded optical and electrical data derived from patch-clamp or other electrode-based recordings. To identify temporal relations between electrical activity patterns we implemented different options to perform cross correlation analysis, demonstrating their utility during voltage imaging in Drosophila and mice. All features combined, NOSA will facilitate the first steps into using GEVIs and help to realize their full potential for revealing cell-type specific connectivity and functional interactions.}, } @article {pmid32762341, year = {2020}, author = {Whelan, CJ and Avdieiev, SS and Gatenby, RA}, title = {Insights From the Ecology of Information to Cancer Control.}, journal = {Cancer control : journal of the Moffitt Cancer Center}, volume = {27}, number = {3}, pages = {1073274820945980}, pmid = {32762341}, issn = {1526-2359}, support = {U54 CA193489/CA/NCI NIH HHS/United States ; }, mesh = {Cytoskeleton/physiology ; *Ecosystem ; Humans ; Integrins/physiology ; Models, Theoretical ; Neoplasms/pathology/*therapy ; Tumor Microenvironment ; }, abstract = {Uniquely in nature, living systems must acquire, store, and act upon information. The survival and replicative fate of each normal cell in a multicellular organism is determined solely by information obtained from its surrounding tissue. In contrast, cancer cells as single-cell eukaryotes live in a disrupted, heterogeneous environment with opportunities and hazards. Thus, cancer cells, unlike normal somatic cells, must constantly obtain information from their environment to ensure survival and proliferation. In this study, we build upon a simple mathematical modeling framework developed to predict (1) how information promotes population persistence in a highly heterogeneous environment and (2) how disruption of information resulting from habitat fragmentation increases the probability of population extinction. Because (1) tumors grow in a highly heterogeneous microenvironment and (2) many cancer therapies fragment tumors into isolated, small cancer cell populations, we identify parallels between these 2 systems and develop ideas for cancer cure based on lessons gleaned from Anthropocene extinctions. In many Anthropocene extinctions, such as that of the North American heath hen (Tympanuchus cupido cupido), a large and widespread population was initially reduced and fragmented owing to overexploitation by humans (a "first strike"). After this, the small surviving populations are vulnerable to extinction from environmental or demographic stochastic disturbances (a "second strike"). Following this analogy, after a tumor is fragmented into small populations of isolated cancer cells by an initial therapy, additional treatment can be applied with the intent of extinction (cure). Disrupting a cancer cell's ability to acquire and use information in a heterogeneous environment may be an important tactic for causing extinction following an effective initial therapy. Thus, information, from the scale of cells within tumors to that of species within ecosystems, can be used to identify vulnerabilities to extinction and opportunities for novel treatment strategies.}, } @article {pmid32738355, year = {2020}, author = {Miller, WB and Baluška, F and Torday, JS}, title = {Cellular senomic measurements in Cognition-Based Evolution.}, journal = {Progress in biophysics and molecular biology}, volume = {156}, number = {}, pages = {20-33}, doi = {10.1016/j.pbiomolbio.2020.07.002}, pmid = {32738355}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Biology/trends ; Cell Communication ; *Cognition ; Homeostasis ; Humans ; Models, Biological ; Thermodynamics ; }, abstract = {All living entities are cognitive and dependent on ambiguous information. Any assessment of that imprecision is necessarily a measuring function. Individual cells measure information to sustain self-referential homeostatic equipoise (self-identity) in juxtaposition to the external environment. The validity of that information is improved by its collective assessment. The reception of cellular information obliges thermodynamic reactions that initiate a self-reinforcing work channel. This expresses as natural cellular engineering and niche constructions which become the complex interrelated tissue ecologies of holobionts. Multicellularity is collaborative cellular information management directed towards the optimization of information quality through its collective measured assessment. Biology and its evolution can now be re-framed as the continuous process of self-referential cellular measurement in the perpetual defense of individual cellular self-identities through the collective form.}, } @article {pmid32731489, year = {2020}, author = {Pajkos, M and Zeke, A and Dosztányi, Z}, title = {Ancient Evolutionary Origin of Intrinsically Disordered Cancer Risk Regions.}, journal = {Biomolecules}, volume = {10}, number = {8}, pages = {}, pmid = {32731489}, issn = {2218-273X}, support = {FIEK16-1-2016-0005//FIEK Grant of the National Research, Development and Innovation Office/International ; ED-18-1-2019-003//ELTE Thematic Excellence Programme supported by the Hungarian Ministry for Innovation and Technology./International ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Evolution, Molecular ; Gene Duplication ; Humans ; Intrinsically Disordered Proteins/chemistry/*genetics ; Mutation ; Neoplasms/*genetics ; Protein Conformation ; Protein Domains ; }, abstract = {Cancer is a heterogeneous genetic disease that alters the proper functioning of proteins involved in key regulatory processes such as cell cycle, DNA repair, survival, or apoptosis. Mutations often accumulate in hot-spots regions, highlighting critical functional modules within these proteins that need to be altered, amplified, or abolished for tumor formation. Recent evidence suggests that these mutational hotspots can correspond not only to globular domains, but also to intrinsically disordered regions (IDRs), which play a significant role in a subset of cancer types. IDRs have distinct functional properties that originate from their inherent flexibility. Generally, they correspond to more recent evolutionary inventions and show larger sequence variations across species. In this work, we analyzed the evolutionary origin of disordered regions that are specifically targeted in cancer. Surprisingly, the majority of these disordered cancer risk regions showed remarkable conservation with ancient evolutionary origin, stemming from the earliest multicellular animals or even beyond. Nevertheless, we encountered several examples where the mutated region emerged at a later stage compared with the origin of the gene family. We also showed the cancer risk regions become quickly fixated after their emergence, but evolution continues to tinker with their genes with novel regulatory elements introduced even at the level of humans. Our concise analysis provides a much clearer picture of the emergence of key regulatory elements in proteins and highlights the importance of taking into account the modular organisation of proteins for the analyses of evolutionary origin.}, } @article {pmid32723540, year = {2020}, author = {Ovsepian, SV and O'Leary, VB and Vesselkin, NP}, title = {Evolutionary origins of chemical synapses.}, journal = {Vitamins and hormones}, volume = {114}, number = {}, pages = {1-21}, doi = {10.1016/bs.vh.2020.04.009}, pmid = {32723540}, issn = {0083-6729}, mesh = {Animals ; *Biological Evolution ; Neurons/*physiology ; Synapses/physiology ; Synaptic Transmission/*genetics/*physiology ; }, abstract = {Synaptic transmission is a fundamental neurobiological process by which neurons interact with each other and non-neuronal cells. It involves release of active substances from the presynaptic neuron onto receptive elements of postsynaptic cells, inducing waves of spreading electrochemical response. While much has been learned about the cellular and molecular mechanisms driving and governing transmitter release and sensing, the evolutionary origin of synaptic connections remains obscure. Herein, we review emerging evidence and concepts suggesting that key components of chemical synapse arose independently from neurons, in different functional and biological contexts, before the rise of multicellular living forms. We argue that throughout evolution, distinct synaptic constituents have been co-opted from ancestral forms for a new role in early metazoan, leading to the rise of chemical synapses and neurotransmission. Such a mosaic model of the origin of chemical synapses agrees with and supports the pluralistic hypothesis of evolutionary change.}, } @article {pmid32717856, year = {2020}, author = {Erber, L and Hoffmann, A and Fallmann, J and Hagedorn, M and Hammann, C and Stadler, PF and Betat, H and Prohaska, S and Mörl, M}, title = {Unusual Occurrence of Two Bona-Fide CCA-Adding Enzymes in Dictyostelium discoideum.}, journal = {International journal of molecular sciences}, volume = {21}, number = {15}, pages = {}, pmid = {32717856}, issn = {1422-0067}, support = {MO 634/8-2; PR 1288/6-2//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Dictyostelium/enzymology/genetics ; *Genome, Protozoan ; *Protozoan Proteins/genetics/metabolism ; *RNA Nucleotidyltransferases/genetics/metabolism ; RNA, Protozoan/genetics/metabolism ; RNA, Transfer/genetics/metabolism ; }, abstract = {Dictyostelium discoideum, the model organism for the evolutionary supergroup of Amoebozoa, is a social amoeba that, upon starvation, undergoes transition from a unicellular to a multicellular organism. In its genome, we identified two genes encoding for tRNA nucleotidyltransferases. Such pairs of tRNA nucleotidyltransferases usually represent collaborating partial activities catalyzing CC- and A-addition to the tRNA 3'-end, respectively. In D. discoideum, however, both enzymes exhibit identical activities, representing bona-fide CCA-adding enzymes. Detailed characterization of the corresponding activities revealed that both enzymes seem to be essential and are regulated inversely during different developmental stages of D. discoideum. Intriguingly, this is the first description of two functionally equivalent CCA-adding enzymes using the same set of tRNAs and showing a similar distribution within the cell. This situation seems to be a common feature in Dictyostelia, as other members of this phylum carry similar pairs of tRNA nucleotidyltransferase genes in their genome.}, } @article {pmid32714346, year = {2020}, author = {Gray, A and Liu, L and Facette, M}, title = {Flanking Support: How Subsidiary Cells Contribute to Stomatal Form and Function.}, journal = {Frontiers in plant science}, volume = {11}, number = {}, pages = {881}, pmid = {32714346}, issn = {1664-462X}, abstract = {Few evolutionary adaptations in plants were so critical as the stomatal complex. This structure allows transpiration and efficient gas exchange with the atmosphere. Plants have evolved numerous distinct stomatal architectures to facilitate gas exchange, while balancing water loss and protection from pathogens that can egress via the stomatal pore. Some plants have simple stomata composed of two kidney-shaped guard cells; however, the stomatal apparatus of many plants includes subsidiary cells. Guard cells and subsidiary cells may originate from a single cell lineage, or subsidiary cells may be recruited from cells adjacent to the guard mother cell. The number and morphology of subsidiary cells varies dramatically, and subsidiary cell function is also varied. Subsidiary cells may support guard cell function by offering a mechanical advantage that facilitates guard cell movements, and/or by acting as a reservoir for water and ions. In other cases, subsidiary cells introduce or enhance certain morphologies (such as sunken stomata) that affect gas exchange. Here we review the diversity of stomatal morphology with an emphasis on multi-cellular stomata that include subsidiary cells. We will discuss how subsidiary cells arise and the divisions that produce them; and provide examples of anatomical, mechanical and biochemical consequences of subsidiary cells on stomatal function.}, } @article {pmid32708448, year = {2020}, author = {Martínez-Soto, D and Ortiz-Castellanos, L and Robledo-Briones, M and León-Ramírez, CG}, title = {Molecular Mechanisms Involved in the Multicellular Growth of Ustilaginomycetes.}, journal = {Microorganisms}, volume = {8}, number = {7}, pages = {}, pmid = {32708448}, issn = {2076-2607}, abstract = {Multicellularity is defined as the developmental process by which unicellular organisms became pluricellular during the evolution of complex organisms on Earth. This process requires the convergence of genetic, ecological, and environmental factors. In fungi, mycelial and pseudomycelium growth, snowflake phenotype (where daughter cells remain attached to their stem cells after mitosis), and fruiting bodies have been described as models of multicellular structures. Ustilaginomycetes are Basidiomycota fungi, many of which are pathogens of economically important plant species. These fungi usually grow unicellularly as yeasts (sporidia), but also as simple multicellular forms, such as pseudomycelium, multicellular clusters, or mycelium during plant infection and under different environmental conditions: Nitrogen starvation, nutrient starvation, acid culture media, or with fatty acids as a carbon source. Even under specific conditions, Ustilago maydis can form basidiocarps or fruiting bodies that are complex multicellular structures. These fungi conserve an important set of genes and molecular mechanisms involved in their multicellular growth. In this review, we will discuss in-depth the signaling pathways, epigenetic regulation, required polyamines, cell wall synthesis/degradation, polarized cell growth, and other cellular-genetic processes involved in the different types of Ustilaginomycetes multicellular growth. Finally, considering their short life cycle, easy handling in the laboratory and great morphological plasticity, Ustilaginomycetes can be considered as model organisms for studying fungal multicellularity.}, } @article {pmid32707067, year = {2020}, author = {Preussger, D and Giri, S and Muhsal, LK and Oña, L and Kost, C}, title = {Reciprocal Fitness Feedbacks Promote the Evolution of Mutualistic Cooperation.}, journal = {Current biology : CB}, volume = {30}, number = {18}, pages = {3580-3590.e7}, doi = {10.1016/j.cub.2020.06.100}, pmid = {32707067}, issn = {1879-0445}, mesh = {*Biological Evolution ; Escherichia coli/*genetics/growth & development/*metabolism ; *Feedback, Physiological ; *Genetic Fitness ; Humans ; *Microbial Interactions ; *Symbiosis ; }, abstract = {Mutually beneficial interactions are ubiquitous in nature and have played a pivotal role for the evolution of life on earth. However, the factors facilitating their emergence remain poorly understood. Here, we address this issue both experimentally and by mathematical modeling using cocultures of auxotrophic strains of Escherichia coli, whose growth depends on a reciprocal exchange of amino acids. Coevolving auxotrophic pairs in a spatially heterogeneous environment for less than 150 generations transformed the initial interaction that was merely based on an exchange of metabolic byproducts into a costly metabolic cooperation, in which both partners increased the amounts of metabolites they produced to benefit their corresponding partner. The observed changes were afforded by the formation of multicellular clusters, within which increased cooperative investments were favored by positive fitness feedbacks among interacting genotypes. Under these conditions, non-cooperative individuals were less fit than cooperative mutants. Together, our results highlight the ease with which mutualistic cooperation can evolve, suggesting similar mechanisms likely operate in natural communities. VIDEO ABSTRACT.}, } @article {pmid32698133, year = {2020}, author = {Yan, JJ and Lee, YC and Tsou, YL and Tseng, YC and Hwang, PP}, title = {Insulin-like growth factor 1 triggers salt secretion machinery in fish under acute salinity stress.}, journal = {The Journal of endocrinology}, volume = {246}, number = {3}, pages = {277-288}, doi = {10.1530/JOE-20-0053}, pmid = {32698133}, issn = {1479-6805}, mesh = {Animals ; Fish Proteins/metabolism ; Insulin-Like Growth Factor I/antagonists & inhibitors/*metabolism ; Oryzias ; Salinity ; Salt Stress ; Signal Transduction/drug effects ; Sodium Chloride/*pharmacology ; }, abstract = {Timely adjustment of osmoregulation upon acute salinity stress is essential for the survival of euryhaline fish. This rapid response is thought to be tightly controlled by hormones; however, there are still questions unanswered. In this work, we tested the hypothesis that the endocrine hormone, insulin-like growth factor 1 (Igf1), a slow-acting hormone, is involved in the activation of salt secretion mechanisms in euryhaline medaka (Oryzias melastigma) during acclimation to acute salinity stress. In response to a 30-ppt seawater (SW) challenge, Na+/Cl- secretion was enhanced within 0.5 h, with concomitant organization of ionocyte multicellular complexes and without changes in expression of major transporters. Igf1 receptor inhibitors significantly impair the Na+/Cl- secretion and ionocyte multicellular complex responses without affecting transporter expression. Thus, Igf1 may activate salt secretion as part of the teleost response to acute salinity stress by exerting effects on transporter function and enhancing the formation of ionocyte multicellular complexes. These findings provide new insights into hormonal control of body fluid ionic/osmotic homeostasis during vertebrate evolution.}, } @article {pmid32693719, year = {2020}, author = {Fisher, RM and Shik, JZ and Boomsma, JJ}, title = {The evolution of multicellular complexity: the role of relatedness and environmental constraints.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1931}, pages = {20192963}, pmid = {32693719}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; Phylogeny ; }, abstract = {A major challenge in evolutionary biology has been to explain the variation in multicellularity across the many independently evolved multicellular lineages, from slime moulds to vertebrates. Social evolution theory has highlighted the key role of relatedness in determining multicellular complexity and obligateness; however, there is a need to extend this to a broader perspective incorporating the role of the environment. In this paper, we formally test Bonner's 1998 hypothesis that the environment is crucial in determining the course of multicellular evolution, with aggregative multicellularity evolving more frequently on land and clonal multicellularity more frequently in water. Using a combination of scaling theory and phylogenetic comparative analyses, we describe multicellular organizational complexity across 139 species spanning 14 independent transitions to multicellularity and investigate the role of the environment in determining multicellular group formation and in imposing constraints on multicellular evolution. Our results, showing that the physical environment has impacted the way in which multicellular groups form, highlight that environmental conditions might have affected the major evolutionary transition to obligate multicellularity.}, } @article {pmid32691527, year = {2020}, author = {Parmentier, T and De Laender, F and Bonte, D}, title = {The topology and drivers of ant-symbiont networks across Europe.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {95}, number = {6}, pages = {1664-1688}, doi = {10.1111/brv.12634}, pmid = {32691527}, issn = {1469-185X}, support = {BOF17/PDO/084//Bijzonder Onderzoeksfonds/International ; 1203020N//Fonds Wetenschappelijk Onderzoek/International ; W0.003.16N//Fonds Wetenschappelijk Onderzoek/International ; }, mesh = {Animals ; *Ants ; Biological Evolution ; Ecosystem ; Phylogeny ; Symbiosis ; }, abstract = {Intimate associations between different species drive community composition across ecosystems. Understanding the ecological and evolutionary drivers of these symbiotic associations is challenging because their structure eventually determines stability and resilience of the entire species network. Here, we compiled a detailed database on naturally occurring ant-symbiont networks in Europe to identify factors that affect symbiont network topology. These networks host an unrivalled diversity of macrosymbiotic associations, spanning the entire mutualism-antagonism continuum, including: (i) myrmecophiles - commensalistic and parasitic arthropods; (ii) trophobionts - mutualistic aphids, scale insects, planthoppers and caterpillars; (iii) social parasites - parasitic ant species; (iv) parasitic helminths; and (v) parasitic fungi. We dissected network topology to investigate what determines host specificity, symbiont species richness, and the capacity of different symbiont types to switch hosts. We found 722 macrosymbionts (multicellular symbionts) associated with European ants. Symbiont type explained host specificity and the average relatedness of the host species. Social parasites were associated with few hosts that were phylogenetically highly related, whereas the other symbiont types interacted with a larger number of hosts across a wider taxonomic distribution. The hosts of trophobionts were the least phylogenetically related across all symbiont types. Colony size, host range and habitat type predicted total symbiont richness: ant hosts with larger colony size, a larger distribution range or with a wider habitat range contained more symbiont species. However, we found that different sets of host factors affected diversity in the different types of symbionts. Ecological factors, such as colony size, host range and niche width predominantly determined myrmecophile species richness, whereas host phylogeny was the most important predictor of mutualistic trophobiont, social parasite and parasitic helminth species richness. Lastly, we found that hosts with a common biogeographic history support a more similar community of symbionts. Phylogenetically related hosts also shared more trophobionts, social parasites and helminths, but not myrmecophiles. Taken together, these results suggest that ecological and evolutionary processes structure host specificity and symbiont richness in large-scale ant-symbiont networks, but these drivers may shift in importance depending on the type of symbiosis. Our findings highlight the potential of well-characterized bipartite networks composed of different types of symbioses to identify candidate processes driving community composition.}, } @article {pmid32689913, year = {2020}, author = {Gonçalves, AP and Heller, J and Rico-Ramírez, AM and Daskalov, A and Rosenfield, G and Glass, NL}, title = {Conflict, Competition, and Cooperation Regulate Social Interactions in Filamentous Fungi.}, journal = {Annual review of microbiology}, volume = {74}, number = {}, pages = {693-712}, doi = {10.1146/annurev-micro-012420-080905}, pmid = {32689913}, issn = {1545-3251}, mesh = {Alleles ; Apoptosis ; Evolution, Molecular ; Fungal Proteins/*genetics/metabolism ; Fungi/classification/*genetics ; *Gene Expression Regulation, Fungal ; Haplotypes ; Microbial Interactions/*genetics/physiology ; Phylogeny ; }, abstract = {Social cooperation impacts the development and survival of species. In higher taxa, kin recognition occurs via visual, chemical, or tactile cues that dictate cooperative versus competitive interactions. In microbes, the outcome of cooperative versus competitive interactions is conferred by identity at allorecognition loci, so-called kind recognition. In syncytial filamentous fungi, the acquisition of multicellularity is associated with somatic cell fusion within and between colonies. However, such intraspecific cooperation entails risks, as fusion can transmit deleterious genotypes or infectious components that reduce fitness, or give rise to cheaters that can exploit communal goods without contributing to their production. Allorecognition mechanisms in syncytial fungi regulate somatic cell fusion by operating precontact during chemotropic interactions, during cell adherence, and postfusion by triggering programmed cell death reactions. Alleles at fungal allorecognition loci are highly polymorphic, fall into distinct haplogroups, and show evolutionary signatures of balancing selection, similar to allorecognition loci across the tree of life.}, } @article {pmid32687894, year = {2020}, author = {Wavreil, FDM and Yajima, M}, title = {Diversity of activator of G-protein signaling (AGS)-family proteins and their impact on asymmetric cell division across taxa.}, journal = {Developmental biology}, volume = {465}, number = {2}, pages = {89-99}, pmid = {32687894}, issn = {1095-564X}, support = {R01 GM126043/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Asymmetric Cell Division/*physiology ; Cell Cycle Proteins/genetics/*metabolism ; Humans ; *Multigene Family ; Signal Transduction/*physiology ; Species Specificity ; Spindle Apparatus/genetics/*metabolism ; }, abstract = {Asymmetric cell division (ACD) is a cellular process that forms two different cell types through a cell division and is thus critical for the development of all multicellular organisms. Not all but many of the ACD processes are mediated by proper orientation of the mitotic spindle, which segregates the fate determinants asymmetrically into daughter cells. In many cell types, the evolutionarily conserved protein complex of Gαi/AGS-family protein/NuMA-like protein appears to play critical roles in orienting the spindle and/or generating the polarized cortical forces to regulate ACD. Studies in various organisms reveal that this conserved protein complex is slightly modified in each phylum or even within species. In particular, AGS-family proteins appear to be modified with a variable number of motifs in their functional domains across taxa. This apparently creates different molecular interactions and mechanisms of ACD in each developmental program, ultimately contributing to developmental diversity across species. In this review, we discuss how a conserved ACD machinery has been modified in each phylum over the course of evolution with a major focus on the molecular evolution of AGS-family proteins and its impact on ACD regulation.}, } @article {pmid32681710, year = {2021}, author = {Rose, CJ}, title = {Germ lines and extended selection during the evolutionary transition to multicellularity.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {336}, number = {8}, pages = {680-686}, doi = {10.1002/jez.b.22985}, pmid = {32681710}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; *Germ Cells ; Life Cycle Stages ; Reproduction ; *Selection, Genetic ; }, abstract = {The major evolutionary transitions from unicellular organisms to multicellularity resulted in a profusion of complex life forms. During the transition from single cells to multicellular life, groups of cells acquired the capacity for reproduction as discrete units; however, the selective causes and underlying mechanisms remain debated. One perspective views the evolution of multicellularity as a shift in the timescale at which natural selection primarily operates-from that of individual cells to the timescale of reproducing groups of cells. Therefore, a distinguishing feature of multicellular reproduction, as opposed to simple growth of a multicellular collective, is that the capacity for reproduction must develop over a timescale that is greater than the reproductive timescale of a single cell. Here, I suggest that the emergence of specialized reproductive cells (the germ line) was an essential first stage of the evolutionary transition to multicellularity because it imposed the necessary "delay"-allowing natural selection to operate over the longer timescale of a multicellular life cycle, ultimately resulting in the evolution of complex multicellular organisms. This perspective highlights the possibility that the ubiquity of a germ-soma distinction among complex multicellular organisms reflects the fact that such life cycles, on first emergence, had the greatest propensity to participate in Darwinian evolution.}, } @article {pmid32677677, year = {2020}, author = {Nedelcu, AM}, title = {The evolution of multicellularity and cancer: views and paradigms.}, journal = {Biochemical Society transactions}, volume = {48}, number = {4}, pages = {1505-1518}, doi = {10.1042/BST20190992}, pmid = {32677677}, issn = {1470-8752}, mesh = {*Biological Evolution ; Humans ; Models, Biological ; Neoplasms/metabolism/*pathology ; Spheroids, Cellular/*metabolism ; Tumor Microenvironment ; }, abstract = {Conceptually and mechanistically, the evolution of multicellularity required the integration of single cells into new functionally, reproductively and evolutionary stable multicellular individuals. As part of this process, a change in levels of selection occurred, with selection at the multicellular level overriding selection at the cell level. The stability of multicellular individuals is dependent on a combination of mechanisms that supress within-group evolution, by both reducing the occurrence of somatic mutations as well as supressing somatic selection. Nevertheless, mutations that, in a particular microenvironment, confer mutant lineages a fitness advantage relative to normal somatic cells do occur, and can result in cancer. This minireview highlights several views and paradigms that relate the evolution of multicellularity to cancer. As a phenomenon, cancer is generally understood as a failure of multicellular systems to suppress somatic evolution. However, as a disease, cancer is interpreted in different frameworks: (i) a breakdown of cooperative behaviors underlying the evolution of multicellularity, (ii) a disruption of molecular networks established during the emergence of multicellularity to impose constraints on single-celled units, or (iii) an atavistic state resulting from reactivating primitive programs that originated in the earliest unicellular species. A number of assumptions are common in all the views relating cancer as a disease to the evolution of multicellularity. For instance, cancer is considered a reversal to unicellularity, and cancer cells are thought to both resemble unicellular organisms and benefit from ancestral-like traits. Nevertheless, potential limitations of current paradigms should be acknowledged as different perspectives can provide novel insights with potential therapeutic implications.}, } @article {pmid32670237, year = {2020}, author = {Gaisin, VA and Kooger, R and Grouzdev, DS and Gorlenko, VM and Pilhofer, M}, title = {Cryo-Electron Tomography Reveals the Complex Ultrastructural Organization of Multicellular Filamentous Chloroflexota (Chloroflexi) Bacteria.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1373}, pmid = {32670237}, issn = {1664-302X}, abstract = {The cell biology of Chloroflexota is poorly studied. We applied cryo-focused ion beam milling and cryo-electron tomography to study the ultrastructural organization of thermophilic Roseiflexus castenholzii and Chloroflexus aggregans, and mesophilic "Ca. Viridilinea mediisalina." These species represent the three main lineages within a group of multicellular filamentous anoxygenic phototrophic Chloroflexota bacteria belonging to the Chloroflexales order. We found surprising structural complexity in the Chloroflexales. As with filamentous cyanobacteria, cells of C. aggregans and "Ca. Viridilinea mediisalina" share the outer membrane-like layers of their intricate multilayer cell envelope. Additionally, cells of R. castenholzii and "Ca. Viridilinea mediisalina" are connected by septal channels that resemble cyanobacterial septal junctions. All three strains possess long pili anchored close to cell-to-cell junctions, a morphological feature comparable to that observed in cyanobacteria. The cytoplasm of the Chloroflexales bacteria is crowded with intracellular organelles such as different types of storage granules, membrane vesicles, chlorosomes, gas vesicles, chemoreceptor-like arrays, and cytoplasmic filaments. We observed a higher level of complexity in the mesophilic strain compared to the thermophilic strains with regards to the composition of intracellular bodies and the organization of the cell envelope. The ultrastructural details that we describe in these Chloroflexales bacteria will motivate further cell biological studies, given that the function and evolution of the many discovered morphological traits remain enigmatic in this diverse and widespread bacterial group.}, } @article {pmid32664620, year = {2020}, author = {Bylino, OV and Ibragimov, AN and Shidlovskii, YV}, title = {Evolution of Regulated Transcription.}, journal = {Cells}, volume = {9}, number = {7}, pages = {}, pmid = {32664620}, issn = {2073-4409}, mesh = {Animals ; Enhancer Elements, Genetic ; *Evolution, Molecular ; *Gene Expression Regulation ; Genome Size ; Humans ; Models, Genetic ; *Transcription, Genetic ; }, abstract = {The genomes of all organisms abound with various cis-regulatory elements, which control gene activity. Transcriptional enhancers are a key group of such elements in eukaryotes and are DNA regions that form physical contacts with gene promoters and precisely orchestrate gene expression programs. Here, we follow gradual evolution of this regulatory system and discuss its features in different organisms. In eubacteria, an enhancer-like element is often a single regulatory element, is usually proximal to the core promoter, and is occupied by one or a few activators. Activation of gene expression in archaea is accompanied by the recruitment of an activator to several enhancer-like sites in the upstream promoter region. In eukaryotes, activation of expression is accompanied by the recruitment of activators to multiple enhancers, which may be distant from the core promoter, and the activators act through coactivators. The role of the general DNA architecture in transcription control increases in evolution. As a whole, it can be seen that enhancers of multicellular eukaryotes evolved from the corresponding prototypic enhancer-like regulatory elements with the gradually increasing genome size of organisms.}, } @article {pmid32659023, year = {2020}, author = {Begum, R and Saran, S}, title = {Glimpses of Dictyostelid research in India.}, journal = {The International journal of developmental biology}, volume = {64}, number = {1-2-3}, pages = {99-107}, doi = {10.1387/ijdb.190208ss}, pmid = {32659023}, issn = {1696-3547}, mesh = {Animals ; *Biological Evolution ; Biomedical Research/*trends ; Cell Differentiation ; Dictyostelium/*physiology ; *Gene Expression Regulation ; India ; Models, Biological ; *Morphogenesis ; }, abstract = {Simple organisms are preferred for understanding the molecular and cellular function(s) of complex processes. Dictyostelium discoideum is a lower eukaryote, a protist and a cellular slime mould, which has been in recent times used for various studies such as cell differentiation, development, cell death, stress responses etc. It is a soil amoeba (unicellular) that undertakes a remarkable, facultative shift to multicellularity when exposed to starvation and requires signal pathways that result in alteration of gene expression and finally show cell differentiation. The amoebae aggregate, differentiate and form fruiting bodies with two terminally differentiated cells: the dead stalk (non-viable) and dormant spores (viable). In India, starting from the isolation of Dictyostelium species to morphogenesis, cell signalling and social evolution has been studied with many more new research additions. Advances in molecular genetics make Dictyostelium an attractive model system to study cell biology, biochemistry, signal transduction and many more.}, } @article {pmid32658971, year = {2020}, author = {Helsen, J and Voordeckers, K and Vanderwaeren, L and Santermans, T and Tsontaki, M and Verstrepen, KJ and Jelier, R}, title = {Gene Loss Predictably Drives Evolutionary Adaptation.}, journal = {Molecular biology and evolution}, volume = {37}, number = {10}, pages = {2989-3002}, pmid = {32658971}, issn = {1537-1719}, mesh = {Adaptation, Biological/*genetics ; *Biological Evolution ; *Gene Deletion ; Gene Regulatory Networks ; *Genetic Fitness ; Oxidative Stress/genetics ; Saccharomyces cerevisiae ; }, abstract = {Loss of gene function is common throughout evolution, even though it often leads to reduced fitness. In this study, we systematically evaluated how an organism adapts after deleting genes that are important for growth under oxidative stress. By evolving, sequencing, and phenotyping over 200 yeast lineages, we found that gene loss can enhance an organism's capacity to evolve and adapt. Although gene loss often led to an immediate decrease in fitness, many mutants rapidly acquired suppressor mutations that restored fitness. Depending on the strain's genotype, some ultimately even attained higher fitness levels than similarly adapted wild-type cells. Further, cells with deletions in different modules of the genetic network followed distinct and predictable mutational trajectories. Finally, losing highly connected genes increased evolvability by facilitating the emergence of a more diverse array of phenotypes after adaptation. Together, our findings show that loss of specific parts of a genetic network can facilitate adaptation by opening alternative evolutionary paths.}, } @article {pmid32653903, year = {2020}, author = {Plachetzki, DC and Pankey, MS and MacManes, MD and Lesser, MP and Walker, CW}, title = {The Genome of the Softshell Clam Mya arenaria and the Evolution of Apoptosis.}, journal = {Genome biology and evolution}, volume = {12}, number = {10}, pages = {1681-1693}, pmid = {32653903}, issn = {1759-6653}, support = {R15 CA104112/CA/NCI NIH HHS/United States ; R35 GM128843/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/*genetics ; *Genes, p53 ; *Genome ; Mya/*genetics ; *Phylogeny ; }, abstract = {Apoptosis is a fundamental feature of multicellular animals and is best understood in mammals, flies, and nematodes, with the invertebrate models being thought to represent a condition of ancestral simplicity. However, the existence of a leukemia-like cancer in the softshell clam Mya arenaria provides an opportunity to re-evaluate the evolution of the genetic machinery of apoptosis. Here, we report the whole-genome sequence for M. arenaria which we leverage with existing data to test evolutionary hypotheses on the origins of apoptosis in animals. We show that the ancestral bilaterian p53 locus, a master regulator of apoptosis, possessed a complex domain structure, in contrast to that of extant ecdysozoan p53s. Further, ecdysozoan taxa, but not chordates or lophotrochozoans like M. arenaria, show a widespread reduction in apoptosis gene copy number. Finally, phylogenetic exploration of apoptosis gene copy number reveals a striking linkage with p53 domain complexity across species. Our results challenge the current understanding of the evolution of apoptosis and highlight the ancestral complexity of the bilaterian apoptotic tool kit and its subsequent dismantlement during the ecdysozoan radiation.}, } @article {pmid32651201, year = {2020}, author = {Klancher, CA and Newman, JD and Ball, AS and van Kessel, JC and Dalia, AB}, title = {Species-Specific Quorum Sensing Represses the Chitobiose Utilization Locus in Vibrio cholerae.}, journal = {Applied and environmental microbiology}, volume = {86}, number = {18}, pages = {}, pmid = {32651201}, issn = {1098-5336}, support = {R35 GM124698/GM/NIGMS NIH HHS/United States ; R35 GM128674/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/*genetics/metabolism ; Disaccharides/*metabolism ; *Operon ; *Quorum Sensing ; Species Specificity ; Vibrio cholerae/*genetics/metabolism ; }, abstract = {The marine facultative pathogen Vibrio cholerae forms complex multicellular communities on the chitinous shells of crustacean zooplankton in its aquatic reservoir. V. cholerae-chitin interactions are critical for the growth, evolution, and waterborne transmission of cholera. This is due, in part, to chitin-induced changes in gene expression in this pathogen. Here, we sought to identify factors that influence chitin-induced expression of one locus, the chitobiose utilization operon (chb), which is required for the uptake and catabolism of the chitin disaccharide. Through a series of genetic screens, we identified that the master regulator of quorum sensing, HapR, is a direct repressor of the chb operon. We also found that the levels of HapR in V. cholerae are regulated by the ClpAP protease. Furthermore, we show that the canonical quorum sensing cascade in V. cholerae regulates chb expression in an HapR-dependent manner. Through this analysis, we found that signaling via the species-specific autoinducer CAI-1, but not the interspecies autoinducer AI-2, influences chb expression. This phenomenon of species-specific regulation may enhance the fitness of this pathogen in its environmental niche.IMPORTANCE In nature, bacteria live in multicellular and multispecies communities. Microbial species can sense the density and composition of their community through chemical cues using a process called quorum sensing (QS). The marine pathogen Vibrio cholerae is found in communities on the chitinous shells of crustaceans in its aquatic reservoir. V. cholerae interactions with chitin are critical for the survival, evolution, and waterborne transmission of this pathogen. Here, we show that V. cholerae uses QS to regulate the expression of one locus required for V. cholerae-chitin interactions.}, } @article {pmid32651001, year = {2021}, author = {Picard, M and Sandi, C}, title = {The social nature of mitochondria: Implications for human health.}, journal = {Neuroscience and biobehavioral reviews}, volume = {120}, number = {}, pages = {595-610}, pmid = {32651001}, issn = {1873-7528}, support = {R01 MH119336/MH/NIMH NIH HHS/United States ; R01 MH122706/MH/NIMH NIH HHS/United States ; R35 GM119793/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Humans ; *Mitochondria ; Social Behavior ; }, abstract = {Sociality has profound evolutionary roots and is observed from unicellular organisms to multicellular animals. In line with the view that social principles apply across levels of biological complexity, a growing body of data highlights the remarkable social nature of mitochondria - life-sustaining endosymbiotic organelles with their own genome that populate the cell cytoplasm. Here, we draw from organizing principles of behavior in social organisms to reveal that similar to individuals among social networks, mitochondria communicate with each other and with the cell nucleus, exhibit group formation and interdependence, synchronize their behaviors, and functionally specialize to accomplish specific functions within the organism. Mitochondria are social organelles. The extension of social principles across levels of biological complexity is a theoretical shift that emphasizes the role of communication and interdependence in cell biology, physiology, and neuroscience. With the help of emerging computational methods capable of capturing complex dynamic behavioral patterns, the implementation of social concepts in mitochondrial biology may facilitate cross-talk across disciplines towards increasingly holistic and accurate models of human health.}, } @article {pmid32649861, year = {2020}, author = {Brunkard, JO}, title = {Exaptive Evolution of Target of Rapamycin Signaling in Multicellular Eukaryotes.}, journal = {Developmental cell}, volume = {54}, number = {2}, pages = {142-155}, pmid = {32649861}, issn = {1878-1551}, support = {DP5 OD023072/OD/NIH HHS/United States ; }, mesh = {Amino Acids/metabolism ; Animals ; Eukaryota/*drug effects/metabolism ; Signal Transduction/*drug effects/physiology ; Sirolimus/*pharmacology ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {Target of rapamycin (TOR) is a protein kinase that coordinates metabolism with nutrient and energy availability in eukaryotes. TOR and its primary interactors, RAPTOR and LST8, have been remarkably evolutionarily static since they arose in the unicellular last common ancestor of plants, fungi, and animals, but the upstream regulatory mechanisms and downstream effectors of TOR signaling have evolved considerable diversity in these separate lineages. Here, I focus on the roles of exaptation and adaptation in the evolution of novel signaling axes in the TOR network in multicellular eukaryotes, concentrating especially on amino acid sensing, cell-cell signaling, and cell differentiation.}, } @article {pmid32643307, year = {2020}, author = {Rose, CJ and Hammerschmidt, K and Pichugin, Y and Rainey, PB}, title = {Meta-population structure and the evolutionary transition to multicellularity.}, journal = {Ecology letters}, volume = {23}, number = {9}, pages = {1380-1390}, doi = {10.1111/ele.13570}, pmid = {32643307}, issn = {1461-0248}, support = {//Marsden Fund Council from government funding administered by the Royal Society of New Zealand/ ; //Marsden Fund/ ; //Royal Society/ ; }, mesh = {Animals ; *Biological Evolution ; Life Cycle Stages ; Phenotype ; *Reproduction ; }, abstract = {The evolutionary transition to multicellularity has occurred on numerous occasions, but transitions to complex life forms are rare. Here, using experimental bacterial populations as proxies for nascent multicellular organisms, we manipulate ecological factors shaping the evolution of groups. Groups were propagated under regimes requiring reproduction via a life cycle replete with developmental and dispersal (propagule) phases, but in one treatment lineages never mixed, whereas in a second treatment, cells from different lineages experienced intense competition during the dispersal phase. The latter treatment favoured traits promoting cell growth at the expense of traits underlying group fitness - a finding that is supported by results from a mathematical model. Our results show that the transition to multicellularity benefits from ecological conditions that maintain discreteness not just of the group (soma) phase, but also of the dispersal (germline) phase.}, } @article {pmid32642048, year = {2020}, author = {Hammarlund, EU}, title = {Harnessing hypoxia as an evolutionary driver of complex multicellularity.}, journal = {Interface focus}, volume = {10}, number = {4}, pages = {20190101}, pmid = {32642048}, issn = {2042-8898}, abstract = {Animal tissue requires low-oxygen conditions for its maintenance. The need for low-oxygen conditions contrasts with the idea of an evolutionary leap in animal diversity as a result of expanding oxic conditions. To accommodate tissue renewal at oxic conditions, however, vertebrate animals and vascular plants demonstrate abilities to access hypoxia. Here, I argue that multicellular organisms sustain oxic conditions first after internalizing hypoxic conditions. The 'harnessing' of hypoxia has allowed multicellular evolution to leave niches that were stable in terms of oxygen concentrations for those where oxygen fluctuates. Since oxygen fluctuates in most settings on Earth's surface, the ancestral niche would have been a deep marine setting. The hypothesis that 'large life' depends on harnessing hypoxia is illustrated in the context of conditions that promote the immature cell phenotype (stemness) in animal physiology and tumour biology and offers one explanation for the general rarity of diverse multicellularity over most of Earth's history.}, } @article {pmid32626570, year = {2020}, author = {Umen, JG}, title = {Volvox and volvocine green algae.}, journal = {EvoDevo}, volume = {11}, number = {}, pages = {13}, pmid = {32626570}, issn = {2041-9139}, abstract = {The transition of life from single cells to more complex multicellular forms has occurred at least two dozen times among eukaryotes and is one of the major evolutionary transitions, but the early steps that enabled multicellular life to evolve and thrive remain poorly understood. Volvocine green algae are a taxonomic group that is uniquely suited to investigating the step-wise acquisition of multicellular organization. The multicellular volvocine species Volvox carteri exhibits many hallmarks of complex multicellularity including complete germ-soma division of labor, asymmetric cell divisions, coordinated tissue-level morphogenesis, and dimorphic sexes-none of which have obvious analogs in its closest unicellular relative, the model alga Chlamydomonas reinhardtii. Here, I summarize some of the key questions and areas of study that are being addressed with Volvox carteri and how increasing genomic information and methodologies for volvocine algae are opening up the entire group as an integrated experimental system for exploring the evolution of multicellularity and more.}, } @article {pmid32617614, year = {2020}, author = {Seoighe, C and Kiniry, SJ and Peters, A and Baranov, PV and Yang, H}, title = {Selection Shapes Synonymous Stop Codon Use in Mammals.}, journal = {Journal of molecular evolution}, volume = {88}, number = {7}, pages = {549-561}, doi = {10.1007/s00239-020-09957-x}, pmid = {32617614}, issn = {1432-1432}, support = {210692/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Codon, Terminator ; *Evolution, Molecular ; Humans ; Mammals/*genetics ; *Models, Genetic ; Phylogeny ; }, abstract = {Phylogenetic models of the evolution of protein-coding sequences can provide insights into the selection pressures that have shaped them. In the application of these models synonymous nucleotide substitutions, which do not alter the encoded amino acid, are often assumed to have limited functional consequences and used as a proxy for the neutral rate of evolution. The ratio of nonsynonymous to synonymous substitution rates is then used to categorize the selective regime that applies to the protein (e.g., purifying selection, neutral evolution, diversifying selection). Here, we extend the Muse and Gaut model of codon evolution to explore the extent of purifying selection acting on substitutions between synonymous stop codons. Using a large collection of coding sequence alignments, we estimate that a high proportion (approximately 57%) of mammalian genes are affected by selection acting on stop codon preference. This proportion varies substantially by codon, with UGA stop codons far more likely to be conserved. Genes with evidence of selection acting on synonymous stop codons have distinctive characteristics, compared to unconserved genes with the same stop codon, including longer [Formula: see text] untranslated regions (UTRs) and shorter mRNA half-life. The coding regions of these genes are also much more likely to be under strong purifying selection pressure. Our results suggest that the preference for UGA stop codons found in many multicellular eukaryotes is selective rather than mutational in origin.}, } @article {pmid32603492, year = {2020}, author = {Liao, X and Wang, J and Zhu, S and Xie, Q and Wang, L and Yu, H and Ye, Z and Yang, C}, title = {Transcriptomic and functional analyses uncover the regulatory role of lncRNA000170 in tomato multicellular trichome formation.}, journal = {The Plant journal : for cell and molecular biology}, volume = {104}, number = {1}, pages = {18-29}, doi = {10.1111/tpj.14902}, pmid = {32603492}, issn = {1365-313X}, mesh = {Gene Expression Profiling ; Solanum lycopersicum/growth & development/*metabolism ; MicroRNAs/metabolism/physiology ; RNA, Long Noncoding/metabolism/*physiology ; RNA, Plant/metabolism/*physiology ; Trichomes/*genetics/metabolism ; }, abstract = {Trichomes are universal specific structures originating from nearly all terrestrial plants. Although quantities of long non-coding RNAs (lncRNAs) have been identified in many plant species, the role of lncRNAs in trichome formation still remains unknown. Here, we identified a total of 1303 lncRNAs in the young stems of woolly mutant LA3560 (Wo) and its non-woolly segregants (WT). Out of these lncRNAs, 86 lncRNAs were obviously upregulated in Wo and 110 lncRNAs were downregulated. We determined that seven lncRNAs were highly expressed in stem trichomes compared to trichome-free stems and several other tissues of LA3560 by a quantitative reverse transcriptase-polymerase chain reaction, including lncRNA000746, lncRNA000170, lncRNA000277, lncRNA000774, lncRNA000756, lncRNA000100, and lncRNA000898. Transgenic experiments revealed that overexpression of lncRNA000170 inhibited type I trichome formation on the lower stems of the adult transgenic plants. We further determined that lncRNA000170 was transcribed from the complementary strand of Solyc10g006360, for which expression can be induced by lncRNA000170 in its overexpression lines and woolly mutants. Solyc10g006360 overexpression also caused type I trichome decrease. In addition, several trichome regulators, such as Wo, H, SlCycB2, and SlCycB3, were markedly downregulated in lncRNA000170 overexpression lines. These findings demonstrate that lncRNA000170 may be involved in the regulatory pathway mediated by these trichome regulators.}, } @article {pmid32602227, year = {2020}, author = {Ryu, C and Walia, A and Ortiz, V and Perry, C and Woo, S and Reeves, BC and Sun, H and Winkler, J and Kanyo, JE and Wang, W and Vukmirovic, M and Ristic, N and Stratton, EA and Meena, SR and Minasyan, M and Kurbanov, D and Liu, X and Lam, TT and Farina, G and Gomez, JL and Gulati, M and Herzog, EL}, title = {Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma-Associated Interstitial Lung Disease.}, journal = {Arthritis & rheumatology (Hoboken, N.J.)}, volume = {72}, number = {11}, pages = {1905-1915}, pmid = {32602227}, issn = {2326-5205}, support = {U01HL112702/HL/NHLBI NIH HHS/United States ; S10-OD-018034-01/HL/NHLBI NIH HHS/United States ; R01 HL152677/HL/NHLBI NIH HHS/United States ; K01-HL1-25474-03/HL/NHLBI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; R01 HL109233/HL/NHLBI NIH HHS/United States ; U01 HL112702/HL/NHLBI NIH HHS/United States ; R01-HL-109233/HL/NHLBI NIH HHS/United States ; R01-HL-125850/HL/NHLBI NIH HHS/United States ; K08 HL151970/HL/NHLBI NIH HHS/United States ; R01 HL153604/HL/NHLBI NIH HHS/United States ; R03 HL154275/HL/NHLBI NIH HHS/United States ; K01 HL125474/HL/NHLBI NIH HHS/United States ; R01 HL125850/HL/NHLBI NIH HHS/United States ; U01-HL-112702/HL/NHLBI NIH HHS/United States ; }, mesh = {Actins/metabolism ; Cytokines/metabolism ; DNA, Mitochondrial/*blood ; Disease Progression ; Female ; Fibroblasts/metabolism ; HEK293 Cells ; Humans ; Lung Diseases, Interstitial/*blood/etiology ; Male ; Scleroderma, Systemic/*blood/complications ; }, abstract = {OBJECTIVE: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterized by variable clinical outcomes, activation of innate immune pattern-recognition receptors (PRRs), and accumulation of α-smooth muscle actin (α-SMA)-expressing myofibroblasts. The aim of this study was to identify an association between these entities and mitochondrial DNA (mtDNA), an endogenous ligand for the intracellular DNA-sensing PRRs Toll-like receptor 9 (TLR-9) and cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING), which has yet to be determined.

METHODS: Human lung fibroblasts (HLFs) from normal donors and SSc-ILD explants were treated with synthetic CpG DNA and assayed for α-SMA expression and extracellular mtDNA using quantitative polymerase chain reaction for the human MT-ATP6 gene. Plasma MT-ATP6 concentrations were evaluated in 2 independent SSc-ILD cohorts and demographically matched controls. The ability of SSc-ILD and control plasma to induce TLR-9 and cGAS/STING activation was evaluated with commercially available HEK 293 reporter cells. Plasma concentrations of type I interferons (IFNs), interleukin-6 (IL-6), and oxidized DNA were measured using electrochemiluminescence and enzyme-linked immunosorbent assay-based methods. Extracellular vesicles (EVs) precipitated from plasma were evaluated for MT-ATP6 concentrations and proteomics via liquid chromatography mass spectrometry.

RESULTS: Normal HLFs and SSc-ILD fibroblasts developed increased α-SMA expression and MT-ATP6 release following CpG stimulation. Plasma mtDNA concentrations were increased in the 2 SSc-ILD cohorts, reflective of ventilatory decline, and were positively associated with both TLR-9 and cGAS/STING activation as well as type I IFN and IL-6 expression. Plasma mtDNA was not oxidized and was conveyed by EVs displaying a proteomics profile consistent with a multicellular origin.

CONCLUSION: These findings demonstrate a previously unrecognized connection between EV-encapsulated mtDNA, clinical outcomes, and intracellular DNA-sensing PRR activation in SSc-ILD. Further study of these interactions could catalyze novel mechanistic and therapeutic insights into SSc-ILD and related disorders.}, } @article {pmid32599749, year = {2020}, author = {Opalek, M and Wloch-Salamon, D}, title = {Aspects of Multicellularity in Saccharomyces cerevisiae Yeast: A Review of Evolutionary and Physiological Mechanisms.}, journal = {Genes}, volume = {11}, number = {6}, pages = {}, pmid = {32599749}, issn = {2073-4425}, mesh = {*Biological Evolution ; Phenotype ; Saccharomyces cerevisiae/*genetics ; }, abstract = {The evolutionary transition from single-celled to multicellular growth is a classic and intriguing problem in biology. Saccharomyces cerevisiae is a useful model to study questions regarding cell aggregation, heterogeneity and cooperation. In this review, we discuss scenarios of group formation and how this promotes facultative multicellularity in S. cerevisiae. We first describe proximate mechanisms leading to aggregation. These mechanisms include staying together and coming together, and can lead to group heterogeneity. Heterogeneity is promoted by nutrient limitation, structured environments and aging. We then characterize the evolutionary benefits and costs of facultative multicellularity in yeast. We summarize current knowledge and focus on the newest state-of-the-art discoveries that will fuel future research programmes aiming to understand facultative microbial multicellularity.}, } @article {pmid32592586, year = {2020}, author = {Lustofin, K and Świątek, P and Stolarczyk, P and Miranda, VFO and Płachno, BJ}, title = {Do food trichomes occur in Pinguicula (Lentibulariaceae) flowers?.}, journal = {Annals of botany}, volume = {126}, number = {6}, pages = {1039-1048}, pmid = {32592586}, issn = {1095-8290}, mesh = {Animals ; Bees ; *Flowers ; Phylogeny ; Pollination ; South America ; *Trichomes ; }, abstract = {BACKGROUND AND AIMS: Floral food bodies (including edible trichomes) are a form of floral reward for pollinators. This type of nutritive reward has been recorded in several angiosperm families: Annonaceae, Araceae, Calycanthaceae, Eupomatiaceae, Himantandraceae, Nymphaeaceae, Orchidaceae, Pandanaceae and Winteraceae. Although these bodies are very diverse in their structure, their cells contain food material: starch grains, protein bodies or lipid droplets. In Pinguicula flowers, there are numerous multicellular clavate trichomes. Previous authors have proposed that these trichomes in the Pinguicula flower play the role of 'futterhaare' ('feeding hairs') and are eaten by pollinators. The main aim of this study was to investigate whether the floral non-glandular trichomes of Pinguicula contain food reserves and thus are a reward for pollinators. The trichomes from the Pinguicula groups, which differ in their taxonomy (species from the subgenera: Temnoceras, Pinguicula and Isoloba) as well as the types of their pollinators (butterflies/flies and bees/hummingbirds), were examined. Thus, it was determined whether there are any connections between the occurrence of food trichomes and phylogeny position or pollination biology. Additionally, we determined the phylogenetic history of edible trichomes and pollinator evolution in the Pinguicula species.

METHODS: The species that were sampled were: Pinguicula moctezumae, P. esseriana, P. moranensis, P. emarginata, P. rectifolia, P. mesophytica, P. hemiepiphytica, P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia, P. gigantea, P. lusitanica, P. alpina and P. vulgaris. Light microscopy, histochemistry, and scanning and transmission electron microscopy were used to address our aims with a phylogenetic perspective based on matK/trnK DNA sequences.

KEY RESULTS: No accumulation of protein bodies or lipid droplets was recorded in the floral non-glandular trichomes of any of the analysed species. Starch grains occurred in the cells of the trichomes of the bee-/fly-pollinated species: P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia and P. gigantea, but not in P. alpina or P. vulgaris. Moreover, starch grains were not recorded in the cells of the trichomes of the Pinguicula species that have long spurs, which are pollinated by Lepidoptera (P. moctezumae, P. esseriana, P. moranensis, P. emarginata and P. rectifolia) or birds (P. mesophytica and P. hemiepihytica), or in species with a small and whitish corolla that self-pollinate (P. lusitanica). The results on the occurrence of edible trichomes and pollinator syndromes were mapped onto a phylogenetic reconstruction of the genus.

CONCLUSION: Floral non-glandular trichomes play the role of edible trichomes in some Pinguicula species (P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia and P. gigantea), which are mainly classified as bee-pollinated species that had originated from Central and South America. It seems that in the Pinguicula that are pollinated by other pollinator groups (Lepidoptera and hummingbirds), the non-glandular trichomes in the flowers play a role other than that of a floral reward for their pollinators. Edible trichomes are symplesiomorphic for the Pinguicula species, and thus do not support a monophyletic group such as a synapomorphy. Nevertheless, edible trichomes are derived and are possibly a specialization for fly and bee pollinators by acting as a food reward for these visitors.}, } @article {pmid32582699, year = {2020}, author = {Dexheimer, PJ and Cochella, L}, title = {MicroRNAs: From Mechanism to Organism.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {409}, pmid = {32582699}, issn = {2296-634X}, abstract = {MicroRNAs (miRNAs) are short, regulatory RNAs that act as post-transcriptional repressors of gene expression in diverse biological contexts. The emergence of small RNA-mediated gene silencing preceded the onset of multicellularity and was followed by a drastic expansion of the miRNA repertoire in conjunction with the evolution of complexity in the plant and animal kingdoms. Along this process, miRNAs became an essential feature of animal development, as no higher metazoan lineage tolerated loss of miRNAs or their associated protein machinery. In fact, ablation of the miRNA biogenesis machinery or the effector silencing factors results in severe embryogenesis defects in every animal studied. In this review, we summarize recent mechanistic insight into miRNA biogenesis and function, while emphasizing features that have enabled multicellular organisms to harness the potential of this broad class of repressors. We first discuss how different mechanisms of regulation of miRNA biogenesis are used, not only to generate spatio-temporal specificity of miRNA production within an animal, but also to achieve the necessary levels and dynamics of expression. We then explore how evolution of the mechanism for small RNA-mediated repression resulted in a diversity of silencing complexes that cause different molecular effects on their targets. Multicellular organisms have taken advantage of this variability in the outcome of miRNA-mediated repression, with differential use in particular cell types or even distinct subcellular compartments. Finally, we present an overview of how the animal miRNA repertoire has evolved and diversified, emphasizing the emergence of miRNA families and the biological implications of miRNA sequence diversification. Overall, focusing on selected animal models and through the lens of evolution, we highlight canonical mechanisms in miRNA biology and their variations, providing updated insight that will ultimately help us understand the contribution of miRNAs to the development and physiology of multicellular organisms.}, } @article {pmid32572049, year = {2020}, author = {Jacqueline, C and Parvy, JP and Rollin, ML and Faugère, D and Renaud, F and Missé, D and Thomas, F and Roche, B}, title = {The role of innate immunity in the protection conferred by a bacterial infection against cancer: study of an invertebrate model.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {10106}, pmid = {32572049}, issn = {2045-2322}, support = {C596/A17196/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Anti-Bacterial Agents/metabolism ; Antimicrobial Cationic Peptides/*metabolism ; Bacteria/genetics ; Bacterial Infections/metabolism ; Drosophila Proteins/metabolism/pharmacology ; Drosophila melanogaster ; Fungi/genetics ; Gene Expression/genetics ; Immunity, Innate/*physiology ; Invertebrates/genetics ; Larva/metabolism/microbiology ; Neoplasms/*immunology/prevention & control ; }, abstract = {All multicellular organisms are exposed to a diversity of infectious agents and to the emergence and proliferation of malignant cells. The protection conferred by some infections against cancer has been recently linked to the production of acquired immunity effectors such as antibodies. However, the evolution of innate immunity as a mechanism to prevent cancer and how it is jeopardized by infections remain poorly investigated. Here, we explored this question by performing experimental infections in two genetically modified invertebrate models (Drosophila melanogaster) that develop invasive or non-invasive neoplastic brain tumors. After quantifying tumor size and antimicrobial peptide gene expression, we found that Drosophila larvae infected with a naturally occurring bacterium had smaller tumors compared to controls and to fungus-infected larvae. This was associated with the upregulation of genes encoding two antimicrobial peptides-diptericin and drosomycin-that are known to be important mediators of tumor cell death. We further confirmed that tumor regression upon infection was associated with an increase in tumor cell death. Thus, our study suggests that infection could have a protective role through the production of antimicrobial peptides that increase tumor cell death. Finally, our study highlights the need to understand the role of innate immune effectors in the complex interactions between infections and cancer cell communities in order to develop innovative cancer treatment strategies.}, } @article {pmid32571576, year = {2020}, author = {Li, XG and Zhang, WJ and Qi, XQ and Wu, LF}, title = {Genome analysis of Crassaminicella sp. SY095, an anaerobic mesophilic marine bacterium isolated from a deep-sea hydrothermal vent on the Southwest Indian Ridge.}, journal = {Marine genomics}, volume = {52}, number = {}, pages = {100733}, doi = {10.1016/j.margen.2019.100733}, pmid = {32571576}, issn = {1876-7478}, mesh = {Anaerobiosis ; Clostridiaceae/*genetics/metabolism ; *Genome, Bacterial ; Hydrothermal Vents/*microbiology ; Indian Ocean ; Whole Genome Sequencing ; }, abstract = {Crassaminicella sp. strain SY095 is an anaerobic mesophilic marine bacterium that was recently isolated from a deep-sea hydrothermal vent on the Southwest Indian Ridge. Here, we present the complete genome sequence of strain SY095. The genome consists of a chromosome of 3,046,753 bp (G + C content of 30.81%) and a plasmid of 36,627 bp (G + C content of 31.29%), encodes 2966 protein, 135 tRNA genes, and 34 rRNA genes. Numerous genes are related to peptide transport, amino acid metabolism, motility, and sporulation. This agrees with the observation that strain SY095 is a spore-forming, motile, and chemoheterotrophic bacterium. Further, the genome harbors multiple prophages that carry all the genes necessary for viral particle synthesis. Some prophages carry additional genes that may be involved in the regulation of sporulation. This is the first reported genome of a bacterium from the genus Crassaminicella, providing insights into the microbial adaptation strategies to the deep-sea hydrothermal vent environment.}, } @article {pmid32562277, year = {2021}, author = {Merle, NS and Singh, P and Rahman, J and Kemper, C}, title = {Integrins meet complement: The evolutionary tip of an iceberg orchestrating metabolism and immunity.}, journal = {British journal of pharmacology}, volume = {178}, number = {14}, pages = {2754-2770}, pmid = {32562277}, issn = {1476-5381}, support = {zia/hl006223//National Institutes of Health (NIH)/ ; }, mesh = {*Complement System Proteins ; Humans ; Immune System ; *Integrins ; }, abstract = {Immunologists have recently realized that there is more to the classic innate immune sensor systems than just mere protection against invading pathogens. It is becoming increasingly clear that such sensors, including the inflammasomes, toll-like receptors, and the complement system, are heavily involved in the regulation of basic cell physiological processes and particularly those of metabolic nature. In fact, their "non-canonical" activities make sense as no system directing immune cell activity can perform such task without the need for energy. Further, many of these ancient immune sensors appeared early and concurrently during evolution, particularly during the developmental leap from the single-cell organisms to multicellularity, and therefore crosstalk heavily with each other. Here, we will review the current knowledge about the emerging cooperation between the major inter-cell communicators, integrins, and the cell-autonomous intracellularly and autocrine-active complement, the complosome, during the regulation of single-cell metabolism. LINKED ARTICLES: This article is part of a themed issue on Canonical and non-canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc.}, } @article {pmid32546936, year = {2020}, author = {Li, L and Liu, D and Liu, A and Li, J and Wang, H and Zhou, J}, title = {Genomic Survey of Tyrosine Kinases Repertoire in Electrophorus electricus With an Emphasis on Evolutionary Conservation and Diversification.}, journal = {Evolutionary bioinformatics online}, volume = {16}, number = {}, pages = {1176934320922519}, pmid = {32546936}, issn = {1176-9343}, abstract = {Tyrosine kinases (TKs) play key roles in the regulation of multicellularity in organisms and involved primarily in cell growth, differentiation, and cell-to-cell communication. Genome-wide characterization of TKs has been conducted in many metazoans; however, systematic information regarding this superfamily in Electrophorus electricus (electric eel) is still lacking. In this study, we identified 114 TK genes in the E electricus genome and investigated their evolution, molecular features, and domain architecture using phylogenetic profiling to gain a better understanding of their similarities and specificity. Our results suggested that the electric eel TK (EeTK) repertoire was shaped by whole-genome duplications (WGDs) and tandem duplication events. Compared with other vertebrate TKs, gene members in Jak, Src, and EGFR subfamily duplicated specifically, but with members lost in Eph, Axl, and Ack subfamily in electric eel. We also conducted an exhaustive survey of TK genes in genomic databases, identifying 1674 TK proteins in 31 representative species covering all the main metazoan lineages. Extensive evolutionary analysis indicated that TK repertoire in vertebrates tended to be remarkably conserved, but the gene members in each subfamily were very variable. Comparative expression profile analysis showed that electric organ tissues and muscle shared a similar pattern with specific highly expressed TKs (ie, epha7, musk, jak1, and pdgfra), suggesting that regulation of TKs might play an important role in specifying an electric organ identity from its muscle precursor. We further identified TK genes exhibiting tissue-specific expression patterns, indicating that members in TKs participated in subfunctionalization representing an evolutionary divergence required for the performance of different tissues. This work generates valuable information for further gene function analysis and identifying candidate TK genes reflecting their unique tissue-function specializations in electric eel.}, } @article {pmid32535731, year = {2020}, author = {Hammarlund, EU and Amend, SR and Pienta, KJ}, title = {The issues with tissues: the wide range of cell fate separation enables the evolution of multicellularity and cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {37}, number = {7}, pages = {62}, pmid = {32535731}, issn = {1559-131X}, support = {2019-05254//Vetenskapsrådet/ ; 690817//H2020 Marie Skłodowska-Curie Actions/ ; U54CA143803//National Cancer Institute/ ; CA163124//National Cancer Institute/ ; CA093900//National Cancer Institute/ ; CA143055//National Cancer Institute/ ; }, mesh = {Animals ; Biological Evolution ; Cell Differentiation/physiology ; Cell Plasticity/physiology ; Cell Survival/physiology ; Ecosystem ; Humans ; Neoplasms/genetics/metabolism/*pathology ; Selection, Genetic ; }, abstract = {Our understanding of the rises of animal and cancer multicellularity face the same conceptual hurdles: what makes the clade originate and what makes it diversify. Between the events of origination and diversification lies complex tissue organization that gave rise to novel functionality for organisms and, unfortunately, for malignant transformation in cells. Tissue specialization with distinctly separated cell fates allowed novel functionality at organism level, such as for vertebrate animals, but also involved trade-offs at the cellular level that are potentially disruptive. These trade-offs are under-appreciated and here we discuss how the wide separation of cell phenotypes may contribute to cancer evolution by (a) how factors can reverse differentiated cells into a window of phenotypic plasticity, (b) the reversal to phenotypic plasticity coupled with asexual reproduction occurs in a way that the host cannot adapt, and (c) the power of the transformation factor correlates to the power needed to reverse tissue specialization. The role of reversed cell fate separation for cancer evolution is strengthened by how some tissues and organisms maintain high cell proliferation and plasticity without developing tumours at a corresponding rate. This demonstrates a potential proliferation paradox that requires further explanation. These insights from the cancer field, which observes tissue evolution in real time and closer than any other field, allow inferences to be made on evolutionary events in animal history. If a sweet spot of phenotypic and reproductive versatility is key to transformation, factors stimulating cell fate separation may have promoted also animal diversification on Earth.}, } @article {pmid32529251, year = {2020}, author = {Buschmann, H and Holzinger, A}, title = {Understanding the algae to land plant transition.}, journal = {Journal of experimental botany}, volume = {71}, number = {11}, pages = {3241-3246}, doi = {10.1093/jxb/eraa196}, pmid = {32529251}, issn = {1460-2431}, mesh = {*Embryophyta ; Evolution, Molecular ; Phylogeny ; *Plants ; }, } @article {pmid32523039, year = {2020}, author = {Duraivelan, K and Samanta, D}, title = {Tracing the evolution of nectin and nectin-like cell adhesion molecules.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9434}, pmid = {32523039}, issn = {2045-2322}, mesh = {Animals ; Cell Adhesion/*genetics/physiology ; Cell Adhesion Molecules/*genetics/metabolism ; Cell Adhesion Molecules, Neuronal/genetics/metabolism ; Cell Line ; Computational Biology/methods ; Evolution, Molecular ; Humans ; Nectins/*genetics/metabolism ; }, abstract = {Nectin and nectin-like cell adhesion molecules (collectively referred as nectin family henceforth) are known to mediate cell-cell adhesion and related functions. While current literature suggests that nectins are prevalent in vertebrates, there are no in-depth analyses regarding the evolution of nectin family as a whole. In this work, we examine the evolutionary origin of the nectin family, using selected multicellular metazoans representing diverse clades whose whole genome sequencing data is available. Our results show that this family may have appeared earlier during metazoan evolution than previously believed. Systematic analyses indicate the order in which various members of nectin family seem to have evolved, with some nectin-like molecules appearing first, followed by the evolution of other members. Furthermore, we also found a few possible ancient homologues of nectins. While our study confirms the previous grouping of the nectin family into nectins and nectin-like molecules, it also shows poliovirus receptor (PVR/nectin-like-5) to possess characteristics that are intermediate between these two groups. Interestingly, except for PVR, the other nectins show surprising sequence conservations across species, suggesting evolutionary constraints due to critical roles played by these proteins.}, } @article {pmid32521019, year = {2020}, author = {Phansopa, C and Dunning, LT and Reid, JD and Christin, PA}, title = {Lateral Gene Transfer Acts As an Evolutionary Shortcut to Efficient C4 Biochemistry.}, journal = {Molecular biology and evolution}, volume = {37}, number = {11}, pages = {3094-3104}, pmid = {32521019}, issn = {1537-1719}, mesh = {Amino Acid Substitution ; *Biological Evolution ; *Gene Transfer, Horizontal ; Phosphoenolpyruvate Carboxylase/*genetics ; Photosynthesis/*genetics ; Poaceae/enzymology/*genetics ; }, abstract = {The adaptation of proteins for novel functions often requires changes in their kinetics via amino acid replacement. This process can require multiple mutations, and therefore extended periods of selection. The transfer of genes among distinct species might speed up the process, by providing proteins already adapted for the novel function. However, this hypothesis remains untested in multicellular eukaryotes. The grass Alloteropsis is an ideal system to test this hypothesis due to its diversity of genes encoding phosphoenolpyruvate carboxylase, an enzyme that catalyzes one of the key reactions in the C4 pathway. Different accessions of Alloteropsis either use native isoforms relatively recently co-opted from other functions or isoforms that were laterally acquired from distantly related species that evolved the C4 trait much earlier. By comparing the enzyme kinetics, we show that native isoforms with few amino acid replacements have substrate KM values similar to the non-C4 ancestral form, but exhibit marked increases in catalytic efficiency. The co-option of native isoforms was therefore followed by rapid catalytic improvements, which appear to rely on standing genetic variation observed within one species. Native C4 isoforms with more amino acid replacements exhibit additional changes in affinities, suggesting that the initial catalytic improvements are followed by gradual modifications. Finally, laterally acquired genes show both strong increases in catalytic efficiency and important changes in substrate handling. We conclude that the transfer of genes among distant species sharing the same physiological novelty creates an evolutionary shortcut toward more efficient enzymes, effectively accelerating evolution.}, } @article {pmid32517626, year = {2020}, author = {Laundon, D and Chrismas, N and Wheeler, G and Cunliffe, M}, title = {Chytrid rhizoid morphogenesis resembles hyphal development in multicellular fungi and is adaptive to resource availability.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1928}, pages = {20200433}, pmid = {32517626}, issn = {1471-2954}, mesh = {Chytridiomycota/*physiology ; Fungi ; Hyphae/*growth & development ; Morphogenesis ; }, abstract = {Key to the ecological prominence of fungi is their distinctive cell biology, our understanding of which has been principally based on dikaryan hyphal and yeast forms. The early-diverging Chytridiomycota (chytrids) are ecologically important and a significant component of fungal diversity, yet their cell biology remains poorly understood. Unlike dikaryan hyphae, chytrids typically attach to substrates and feed osmotrophically via anucleate rhizoids. The evolution of fungal hyphae appears to have occurred from rhizoid-bearing lineages and it has been hypothesized that a rhizoid-like structure was the precursor to multicellular hyphae. Here, we show in a unicellular chytrid, Rhizoclosmatium globosum, that rhizoid development exhibits striking similarities with dikaryan hyphae and is adaptive to resource availability. Rhizoid morphogenesis exhibits analogous patterns to hyphal growth and is controlled by β-glucan-dependent cell wall synthesis and actin polymerization. Chytrid rhizoids growing from individual cells also demonstrate adaptive morphological plasticity in response to resource availability, developing a searching phenotype when carbon starved and spatial differentiation when interacting with particulate organic matter. We demonstrate that the adaptive cell biology and associated developmental plasticity considered characteristic of hyphal fungi are shared more widely across the Kingdom Fungi and therefore could be conserved from their most recent common ancestor.}, } @article {pmid32514997, year = {2020}, author = {Villagra, C and Frías-Lasserre, D}, title = {Epigenetic Molecular Mechanisms in Insects.}, journal = {Neotropical entomology}, volume = {49}, number = {5}, pages = {615-642}, doi = {10.1007/s13744-020-00777-8}, pmid = {32514997}, issn = {1678-8052}, mesh = {*Adaptation, Physiological ; Animals ; *Epigenesis, Genetic ; Insecta/*genetics ; Life Cycle Stages ; Phenotype ; Social Behavior ; }, abstract = {Insects are the largest animal group on Earth both in biomass and diversity. Their outstanding success has inspired genetics and developmental research, allowing the discovery of dynamic process explaining extreme phenotypic plasticity and canalization. Epigenetic molecular mechanisms (EMMs) are vital for several housekeeping functions in multicellular organisms, regulating developmental, ontogenetic trajectories and environmental adaptations. In Insecta, EMMs are involved in the development of extreme phenotypic divergences such as polyphenisms and eusocial castes. Here, we review the history of this research field and how the main EMMs found in insects help to understand their biological processes and diversity. EMMs in insects confer them rapid response capacity allowing insect either to change with plastic divergence or to keep constant when facing different stressors or stimuli. EMMs function both at intra as well as transgenerational scales, playing important roles in insect ecology and evolution. We discuss on how EMMs pervasive influences in Insecta require not only the control of gene expression but also the dynamic interplay of EMMs with further regulatory levels, including genetic, physiological, behavioral, and environmental among others, as was earlier proposed by the Probabilistic Epigenesis model and Developmental System Theory.}, } @article {pmid32510705, year = {2020}, author = {Palmer, MA and Nelson, CM}, title = {Fusion of airways during avian lung development constitutes a novel mechanism for the formation of continuous lumena in multicellular epithelia.}, journal = {Developmental dynamics : an official publication of the American Association of Anatomists}, volume = {249}, number = {11}, pages = {1318-1333}, doi = {10.1002/dvdy.215}, pmid = {32510705}, issn = {1097-0177}, support = {CA187692/CA/NCI NIH HHS/United States ; HL110335/HL/NHLBI NIH HHS/United States ; HL118532/HL/NHLBI NIH HHS/United States ; HL120142/HL/NHLBI NIH HHS/United States ; CMMI-1435853//National Science Foundation/International ; //Camille & Henry Dreyfus Foundation/International ; //David & Lucile Packard Foundation/International ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Basement Membrane/cytology/*embryology ; Chick Embryo ; *Chickens ; Lung/cytology/*embryology ; Respiratory Mucosa/cytology/*embryology ; }, abstract = {BACKGROUND: During development of the avian lung, the initially terminally branched epithelial tree later forms a continuous network of airways. This occurs via a large-scale epithelial fusion event, wherein airways that originate proximally collide with those that originate distally to form one continuous lumen.

RESULTS: Here, we found that prior to fusion, the epithelium of the embryonic chicken lung undergoes a shape change to permit the initiation and extension of new branches which contain the cells that initiate contact. These changes in epithelial shape coincide with the differentiation of smooth muscle cells that wrap the airways. From these nascent epithelial branches, individual cells form cytoskeletal protrusions that extend toward and form a bridge with their target airway. Additional cells then join the fusion site, forming a bilayered epithelium. During this process, the basement membrane around the prefusion epithelium degrades and then reforms after fusion. The epithelial bilayer then undergoes apoptosis, clearing the path between the two lumens.

CONCLUSIONS: The process of airway epithelial fusion in the developing chicken lung constitutes a novel mechanism for the generation of complex multicellular tubes and suggests a conserved role for smooth muscle in the shaping of airway epithelia.}, } @article {pmid32505051, year = {2020}, author = {Oates, AC}, title = {Waiting on the Fringe: cell autonomy and signaling delays in segmentation clocks.}, journal = {Current opinion in genetics & development}, volume = {63}, number = {}, pages = {61-70}, doi = {10.1016/j.gde.2020.04.008}, pmid = {32505051}, issn = {1879-0380}, mesh = {Animals ; *Body Patterning ; *Embryonic Development ; Membrane Proteins/*metabolism ; *Models, Biological ; Signal Transduction ; Vertebrates/*physiology ; }, abstract = {The rhythmic and sequential segmentation of the vertebrate body axis into somites during embryogenesis is governed by a multicellular, oscillatory patterning system called the segmentation clock. Despite many overt similarities between vertebrates, differences in genetic and dynamic regulation have been reported, raising intriguing questions about the evolution and conservation of this fundamental patterning process. Recent studies have brought insights into two important and related issues: (1) whether individual cells of segmentation clocks are autonomous oscillators or require cell-cell communication for their rhythm; and (2) the role of delays in the cell-cell communication that synchronizes the population of genetic oscillators. Although molecular details differ between species, conservation may exist at the level of the dynamics, hinting at rules for evolutionary trajectories in the system.}, } @article {pmid32499560, year = {2020}, author = {Tang, M and Xie, Q and Gimple, RC and Zhong, Z and Tam, T and Tian, J and Kidwell, RL and Wu, Q and Prager, BC and Qiu, Z and Yu, A and Zhu, Z and Mesci, P and Jing, H and Schimelman, J and Wang, P and Lee, D and Lorenzini, MH and Dixit, D and Zhao, L and Bhargava, S and Miller, TE and Wan, X and Tang, J and Sun, B and Cravatt, BF and Muotri, AR and Chen, S and Rich, JN}, title = {Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions.}, journal = {Cell research}, volume = {30}, number = {10}, pages = {833-853}, pmid = {32499560}, issn = {1748-7838}, support = {F30 CA217065/CA/NCI NIH HHS/United States ; R21 AR074763/AR/NIAMS NIH HHS/United States ; RC2 DK114785/DK/NIDDK NIH HHS/United States ; R01 CA238662/CA/NCI NIH HHS/United States ; F30 CA217066/CA/NCI NIH HHS/United States ; R01 CA169117/CA/NCI NIH HHS/United States ; P30 NS047101/NS/NINDS NIH HHS/United States ; R01 CA171652/CA/NCI NIH HHS/United States ; R01 NS089272/NS/NINDS NIH HHS/United States ; R01 NS087913/NS/NINDS NIH HHS/United States ; U19 MH107367/MH/NIMH NIH HHS/United States ; R01 NS103434/NS/NINDS NIH HHS/United States ; R24 DK099810/DK/NIDDK NIH HHS/United States ; F31 CA243296/CA/NCI NIH HHS/United States ; R35 CA197718/CA/NCI NIH HHS/United States ; R33 HD090662/HD/NICHD NIH HHS/United States ; R01 EB021857/EB/NIBIB NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; R01 CA154130/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bioprinting ; Cell Line, Tumor ; Cell Proliferation ; Glioblastoma/*immunology ; Humans ; Mice ; Neural Stem Cells ; Tissue Scaffolds ; Tumor Microenvironment/*immunology ; }, abstract = {Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment.}, } @article {pmid32496191, year = {2020}, author = {Booth, DS and King, N}, title = {Genome editing enables reverse genetics of multicellular development in the choanoflagellate Salpingoeca rosetta.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32496191}, issn = {2050-084X}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {CRISPR-Cas Systems ; Choanoflagellata/*genetics/*growth & development ; Gene Editing ; Genome, Protozoan ; Lectins, C-Type/genetics ; Protozoan Proteins/genetics ; Reverse Genetics/*methods ; }, abstract = {In a previous study, we established a forward genetic screen to identify genes required for multicellular development in the choanoflagellate, Salpingoeca rosetta (Levin et al., 2014). Yet, the paucity of reverse genetic tools for choanoflagellates has hampered direct tests of gene function and impeded the establishment of choanoflagellates as a model for reconstructing the origin of their closest living relatives, the animals. Here we establish CRISPR/Cas9-mediated genome editing in S. rosetta by engineering a selectable marker to enrich for edited cells. We then use genome editing to disrupt the coding sequence of a S. rosetta C-type lectin gene, rosetteless, and thereby demonstrate its necessity for multicellular rosette development. This work advances S. rosetta as a model system in which to investigate how genes identified from genetic screens and genomic surveys function in choanoflagellates and evolved as critical regulators of animal biology.}, } @article {pmid32491889, year = {2020}, author = {Nguyen, M and Shiferaw, Y}, title = {Feedback control of calcium driven alternans in cardiac myocytes.}, journal = {Chaos (Woodbury, N.Y.)}, volume = {30}, number = {5}, pages = {053106}, pmid = {32491889}, issn = {1089-7682}, support = {R01 HL119095/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Calcium Signaling/*physiology ; Feedback ; Glucans/antagonists & inhibitors ; Myocytes, Cardiac/*physiology ; Ventricular Fibrillation ; }, abstract = {Cardiac alternans is a beat-to-beat alternation of the action potential duration (APD), which has been implicated as a possible cause of ventricular fibrillation. Previous studies have shown that alternans can originate via a period doubling bifurcation caused by the nonlinear dependence of the APD on the previous diastolic interval. In this case, it has been demonstrated that alternans can be eliminated by applying feedback control on the pacing cycle length. However, studies have shown that alternans can also originate due to unstable calcium (Ca) cycling in cardiac myocytes. In this study, we explore the effectiveness of APD feedback control to suppress alternans when the underlying instability is due to unstable Ca cycling. In particular, we explore the role of the bi-directional coupling between Ca and voltage and determine the effectiveness of feedback control under a wide range of conditions. We also analyze the applicability of feedback control on a coupled two cell system and show that APD control induces spatially out-of-phase alternans. We analyze the onset and the necessary conditions for the emergence of these out-of-phase patterns and assess the effectiveness of feedback control to suppress Ca driven alternans in a multi-cellular system.}, } @article {pmid32472019, year = {2020}, author = {Lawal, HM and Schilde, C and Kin, K and Brown, MW and James, J and Prescott, AR and Schaap, P}, title = {Cold climate adaptation is a plausible cause for evolution of multicellular sporulation in Dictyostelia.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {8797}, pmid = {32472019}, issn = {2045-2322}, support = {100293/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; BB/K000799/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Acclimatization ; Biological Evolution ; Cold Climate ; Dictyostelium/*classification/*physiology ; Fossils/*parasitology ; Phylogeny ; Spores/physiology ; }, abstract = {Unicellular protozoa that encyst individually upon starvation evolved at least eight times into organisms that instead form multicellular fruiting bodies with spores. The Dictyostelia are the largest and most complex group of such organisms. They can be subdivided into 4 major groups, with many species in groups 1-3 having additionally retained encystment. To understand fitness differences between spores and cysts, we measured long-term survival of spores and cysts under climate-mimicking conditions, investigated spore and cyst ultrastructure, and related fitness characteristics to species ecology. We found that spores and cysts survived 22 °C equally well, but that spores survived wet and dry frost better than cysts, with group 4 spores being most resilient. Spore walls consist of three layers and those of cysts of maximally two, while spores were also more compacted than cysts, with group 4 spores being the most compacted. Group 4 species were frequently isolated from arctic and alpine zones, which was rarely the case for group 1-3 species. We inferred a fossil-calibrated phylogeny of Dictyostelia, which showed that its two major branches diverged 0.52 billion years ago, following several global glaciations. Our results suggest that Dictyostelium multicellular sporulation was a likely adaptation to a cold climate.}, } @article {pmid32471172, year = {2020}, author = {Demin, SI and Bogolyubov, DS and Granovitch, AI and Mikhailova, NA}, title = {New data on spermatogenic cyst formation and cellular composition of the testis in a marine gastropod, Littorina saxatilis.}, journal = {International journal of molecular sciences}, volume = {21}, number = {11}, pages = {}, pmid = {32471172}, issn = {1422-0067}, support = {АААА-А17-117122790092-9//Russian Academy of Sciences/ ; 19-14-00321//Russian Science Support Foundation/ ; 0.40.491.2017//St. Petersburg State University/ ; }, mesh = {Animals ; Gastropoda/*cytology ; Male ; Spermatogonia/ultrastructure ; Testis/*cytology ; }, abstract = {Knowledge of the testis structure is important for gastropod taxonomy and phylogeny, particularly for the comparative analysis of sympatric Littorina species. Observing fresh tissue and squashing fixed tissue with gradually increasing pressure, we have recently described a peculiar type of cystic spermatogenesis, rare in mollusks. It has not been documented in most mollusks until now. The testis of adult males consists of numerous lobules filled with multicellular cysts containing germline cells at different stages of differentiation. Each cyst is formed by one cyst cell of somatic origin. Here, we provide evidence for the existence of two ways of cyst formation in Littorina saxatilis. One of them begins with a goniablast cyst formation; it somewhat resembles cyst formation in Drosophila testes. The second way begins with capture of a free spermatogonium by the polyploid cyst cell which is capable to move along the gonad tissues. This way of cyst formation has not been described previously. Our data expand the understanding of the diversity of spermatogenesis types in invertebrates.}, } @article {pmid32471018, year = {2020}, author = {Kuroiwa, A}, title = {Enhancers, development, and evolution.}, journal = {Development, growth & differentiation}, volume = {62}, number = {5}, pages = {265-268}, doi = {10.1111/dgd.12683}, pmid = {32471018}, issn = {1440-169X}, mesh = {Animals ; *Biological Evolution ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation, Developmental/*genetics ; Germ Layers ; }, abstract = {A single-celled fertilized egg develops into a complex, multicellular animal through a series of selection processes of developmental pathways. During these processes, regulatory genes exhibit spatiotemporally restricted expression under the control of the species-specific genetic program, and dictate developmental processes from germ layer formation to cellular differentiation. Elucidation of molecular mechanisms underlying developmental processes and also of mechanistic bases for morphological diversification during evolution is one of the central issues in contemporary developmental biology. Progress has been made due to recent technological innovations, such as high-throughput nucleotide sequencing, live-cell imaging, efficient genetic manipulation, and establishment of the organoid system, opening new avenues to the above issues.}, } @article {pmid32463355, year = {2020}, author = {Kuncha, SK and Venkadasamy, VL and Amudhan, G and Dahate, P and Kola, SR and Pottabathini, S and Kruparani, SP and Shekar, PC and Sankaranarayanan, R}, title = {Genomic innovation of ATD alleviates mistranslation associated with multicellularity in Animalia.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32463355}, issn = {2050-084X}, support = {DST-INSPIRE//Department of Science and Technology, Ministry of Science and Technology/International ; J. C. Bose Fellowship//Science and Engineering Research Board/International ; Centre of Excellence//Department of Biotechnology , Ministry of Science and Technology/International ; Healthcare Theme project//Council of Scientific and Industrial Research/International ; Centre of Excellence//Department of Biotechnology, Ministry of Science and Technology/International ; }, mesh = {Amino Acyl-tRNA Synthetases/genetics/metabolism ; Animals ; Biological Evolution ; Cell Line ; Choanoflagellata/enzymology/genetics/metabolism ; Eukaryota/*enzymology/*genetics/metabolism ; Genome ; Genomics ; Humans ; Hydrolases/genetics/*metabolism ; Mice ; Oxidative Stress ; *Protein Biosynthesis ; RNA, Transfer/genetics/metabolism ; Threonine/metabolism ; }, abstract = {The emergence of multicellularity in Animalia is associated with increase in ROS and expansion of tRNA-isodecoders. tRNA expansion leads to misselection resulting in a critical error of L-Ala mischarged onto tRNA[Thr], which is proofread by Animalia-specific-tRNA Deacylase (ATD) in vitro. Here we show that in addition to ATD, threonyl-tRNA synthetase (ThrRS) can clear the error in cellular scenario. This two-tier functional redundancy for translation quality control breaks down during oxidative stress, wherein ThrRS is rendered inactive. Therefore, ATD knockout cells display pronounced sensitivity through increased mistranslation of threonine codons leading to cell death. Strikingly, we identify the emergence of ATD along with the error inducing tRNA species starting from Choanoflagellates thus uncovering an important genomic innovation required for multicellularity that occurred in unicellular ancestors of animals. The study further provides a plausible regulatory mechanism wherein the cellular fate of tRNAs can be switched from protein biosynthesis to non-canonical functions.}, } @article {pmid32462426, year = {2020}, author = {Casanova, JL and Abel, L}, title = {The human genetic determinism of life-threatening infectious diseases: genetic heterogeneity and physiological homogeneity?.}, journal = {Human genetics}, volume = {139}, number = {6-7}, pages = {681-694}, pmid = {32462426}, issn = {1432-1203}, support = {UL1 TR001866/TR/NCATS NIH HHS/United States ; R21 AI137371/AI/NIAID NIH HHS/United States ; R37 AI095983/AI/NIAID NIH HHS/United States ; R01 AI127564/AI/NIAID NIH HHS/United States ; R01 NS072381/NS/NINDS NIH HHS/United States ; U19 AI111143/AI/NIAID NIH HHS/United States ; R01 AI088364/AI/NIAID NIH HHS/United States ; P01 AI061093/AI/NIAID NIH HHS/United States ; }, mesh = {Communicable Diseases/*genetics/immunology/*pathology ; *Genetic Heterogeneity ; *Genetic Predisposition to Disease ; Humans ; Models, Genetic ; }, abstract = {Multicellular eukaryotes emerged late in evolution from an ocean of viruses, bacteria, archaea, and unicellular eukaryotes. These macroorganisms are exposed to and infected by a tremendous diversity of microorganisms. Those that are large enough can even be infected by multicellular fungi and parasites. Each interaction is unique, if only because it operates between two unique living organisms, in an infinite diversity of circumstances. This is neatly illustrated by the extraordinarily high level of interindividual clinical variability in human infections, even for a given pathogen, ranging from a total absence of clinical manifestations to death. We discuss here the idea that the determinism of human life-threatening infectious diseases can be governed by single-gene inborn errors of immunity, which are rarely Mendelian and frequently display incomplete penetrance. We briefly review the evidence in support of this notion obtained over the last two decades, referring to a number of focused and thorough reviews published by eminent colleagues in this issue of Human Genetics. It seems that almost any life-threatening infectious disease can be driven by at least one, and, perhaps, a great many diverse monogenic inborn errors, which may nonetheless be immunologically related. While the proportions of monogenic cases remain unknown, a picture in which genetic heterogeneity is combined with physiological homogeneity is emerging from these studies. A preliminary sketch of the human genetic architecture of severe infectious diseases is perhaps in sight.}, } @article {pmid32455681, year = {2020}, author = {Kim, SK and Jang, SD and Kim, H and Chung, S and Park, JK and Kuh, HJ}, title = {Phenotypic Heterogeneity and Plasticity of Cancer Cell Migration in a Pancreatic Tumor Three-Dimensional Culture Model.}, journal = {Cancers}, volume = {12}, number = {5}, pages = {}, pmid = {32455681}, issn = {2072-6694}, support = {2019R1A5A2027588//National Research Foundation of Korea/ ; 2019R1A2B5B02070524//National Research Foundation of Korea/ ; }, abstract = {Invasive cancer cell migration is a key feature of metastatic human pancreatic ductal adenocarcinoma (PDAC), yet the underlying mechanisms remain poorly understood. Here, we investigated modes of cancer cell invasion using two pancreatic cancer cell lines with differential epithelial-mesenchymal status, PANC-1 and BxPC-3, under 3D culture conditions. Multicellular tumor spheroids (TSs) were grown in a collagen matrix co-cultured with pancreatic stellate cells (PSCs) using microchannel chips. PANC-1 cells showed individual migration from TSs via invadopodium formation. BxPC-3 cells showed plasticity between collective and individual migration in either mesenchymal mode, with filopodium-like protrusions, or blebby amoeboid mode. These two cell lines showed significantly different patterns of extracellular matrix (ECM) remodeling, with MMP-dependent degradation in a limited area of ECM around invadopodia for PANC-1 cells, or MMP-independent extensive deformation of ECM for BxPC-3 cells. Cancer cell migration out of the collagen channel significantly increased by PSCs and directional cancer cell migration was mediated by fibronectin deposited by PSCs. Our results highlight the phenotypic heterogeneity and plasticity of PDAC cell migration and ECM remodeling under 3D culture conditions. This 3D co-culture model of pancreatic cancer cells and PSCs offers a useful tool for studying cancer cell migration and ECM remodeling to identify and develop potential molecular targets and anti-cancer agents against human PDAC.}, } @article {pmid32455487, year = {2020}, author = {Kumler, WE and Jorge, J and Kim, PM and Iftekhar, N and Koehl, MAR}, title = {Does Formation of Multicellular Colonies by Choanoflagellates Affect Their Susceptibility to Capture by Passive Protozoan Predators?.}, journal = {The Journal of eukaryotic microbiology}, volume = {67}, number = {5}, pages = {555-565}, doi = {10.1111/jeu.12808}, pmid = {32455487}, issn = {1550-7408}, mesh = {Choanoflagellata/*cytology ; *Food Chain ; Stramenopiles/*physiology ; }, abstract = {Microbial eukaryotes, critical links in aquatic food webs, are unicellular, but some, such as choanoflagellates, form multicellular colonies. Are there consequences to predator avoidance of being unicellular vs. forming larger colonies? Choanoflagellates share a common ancestor with animals and are used as model organisms to study the evolution of multicellularity. Escape in size from protozoan predators is suggested as a selective factor favoring evolution of multicellularity. Heterotrophic protozoans are categorized as suspension feeders, motile raptors, or passive predators that eat swimming prey which bump into them. We focused on passive predation and measured the mechanisms responsible for the susceptibility of unicellular vs. multicellular choanoflagellates, Salpingoeca helianthica, to capture by passive heliozoan predators, Actinosphaerium nucleofilum, which trap prey on axopodia radiating from the cell body. Microvideography showed that unicellular and colonial choanoflagellates entered the predator's capture zone at similar frequencies, but a greater proportion of colonies contacted axopodia. However, more colonies than single cells were lost during transport by axopodia to the cell body. Thus, feeding efficiency (proportion of prey entering the capture zone that were engulfed in phagosomes) was the same for unicellular and multicellular prey, suggesting that colony formation is not an effective defense against such passive predators.}, } @article {pmid32450967, year = {2020}, author = {McQueen, E and Rebeiz, M}, title = {On the specificity of gene regulatory networks: How does network co-option affect subsequent evolution?.}, journal = {Current topics in developmental biology}, volume = {139}, number = {}, pages = {375-405}, pmid = {32450967}, issn = {1557-8933}, support = {R01 GM112758/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Body Patterning/*genetics ; Evolution, Molecular ; *Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Humans ; Models, Genetic ; Organ Specificity/*genetics ; Regulatory Elements, Transcriptional/*genetics ; Transcription Factors/*genetics/metabolism ; }, abstract = {The process of multicellular organismal development hinges upon the specificity of developmental programs: for different parts of the organism to form unique features, processes must exist to specify each part. This specificity is thought to be hardwired into gene regulatory networks, which activate cohorts of genes in particular tissues at particular times during development. However, the evolution of gene regulatory networks sometimes occurs by mechanisms that sacrifice specificity. One such mechanism is network co-option, in which existing gene networks are redeployed in new developmental contexts. While network co-option may offer an efficient mechanism for generating novel phenotypes, losses of tissue specificity at redeployed network genes could restrict the ability of the affected traits to evolve independently. At present, there has not been a detailed discussion regarding how tissue specificity of network genes might be altered due to gene network co-option at its initiation, as well as how trait independence can be retained or restored after network co-option. A lack of clarity about network co-option makes it more difficult to speculate on the long-term evolutionary implications of this mechanism. In this review, we will discuss the possible initial outcomes of network co-option, outline the mechanisms by which networks may retain or subsequently regain specificity after network co-option, and comment on some of the possible evolutionary consequences of network co-option. We place special emphasis on the need to consider selectively-neutral outcomes of network co-option to improve our understanding of the role of this mechanism in trait evolution.}, } @article {pmid32444651, year = {2020}, author = {Heaton, LLM and Jones, NS and Fricker, MD}, title = {A mechanistic explanation of the transition to simple multicellularity in fungi.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {2594}, pmid = {32444651}, issn = {2041-1723}, mesh = {Carbon/metabolism ; Cytoplasm/metabolism ; Fungi/*cytology/growth & development/*physiology ; Hyphae/cytology/growth & development ; *Models, Biological ; Nitrogen/metabolism ; Phosphorus/metabolism ; }, abstract = {Development of multicellularity was one of the major transitions in evolution and occurred independently multiple times in algae, plants, animals, and fungi. However recent comparative genome analyses suggest that fungi followed a different route to other eukaryotic lineages. To understand the driving forces behind the transition from unicellular fungi to hyphal forms of growth, we develop a comparative model of osmotrophic resource acquisition. This predicts that whenever the local resource is immobile, hard-to-digest, and nutrient poor, hyphal osmotrophs outcompete motile or autolytic unicellular osmotrophs. This hyphal advantage arises because transporting nutrients via a contiguous cytoplasm enables continued exploitation of remaining resources after local depletion of essential nutrients, and more efficient use of costly exoenzymes. The model provides a mechanistic explanation for the origins of multicellular hyphal organisms, and explains why fungi, rather than unicellular bacteria, evolved to dominate decay of recalcitrant, nutrient poor substrates such as leaf litter or wood.}, } @article {pmid32438974, year = {2020}, author = {Yang, S and Qu, G and Fu, B and Yang, F and Zeng, W and Cai, Y and Ye, T and Yang, Y and Deng, X and Xiang, W and Peng, D and Zhou, B}, title = {The function of KptA/Tpt1 gene - a minor review.}, journal = {Functional plant biology : FPB}, volume = {47}, number = {7}, pages = {577-591}, doi = {10.1071/FP19159}, pmid = {32438974}, issn = {1445-4416}, mesh = {NAD ; Phosphotransferases (Alcohol Group Acceptor) ; RNA, Transfer ; Saccharomyces cerevisiae/genetics ; *Saccharomyces cerevisiae Proteins ; }, abstract = {Rapid response of uni- and multicellular organisms to environmental changes and their own growth is achieved through a series of molecular mechanisms, often involving modification of macromolecules, including nucleic acids, proteins and lipids. The ADP-ribosylation process has ability to modify these different macromolecules in cells, and is closely related to the biological processes, such as DNA replication, transcription, signal transduction, cell division, stress, microbial aging and pathogenesis. In addition, tRNA plays an essential role in the regulation of gene expression, as effector molecules, no-load tRNA affects the overall gene expression level of cells under some nutritional stress. KptA/Tpt1 is an essential phosphotransferase in the process of pre-tRNA splicing, releasing mature tRNA and participating in ADP-ribose. The objective of this review is concluding the gene structure, the evolution history and the function of KptA/Tpt1 from prokaryote to eukaryote organisms. At the same time, the results of promoter elements analysis were also shown in the present study. Moreover, the problems in the function of KptA/Tpt1 that have not been clarified at the present time are summarised, and some suggestions to solve those problems are given. This review presents no only a summary of clear function of KptA/Tpt1 in the process of tRNA splicing and ADP-ribosylation of organisms, but also gives some proposals to clarify unclear problems of it in the future.}, } @article {pmid32431731, year = {2020}, author = {Krueger-Hadfield, SA}, title = {What's ploidy got to do with it? Understanding the evolutionary ecology of macroalgal invasions necessitates incorporating life cycle complexity.}, journal = {Evolutionary applications}, volume = {13}, number = {3}, pages = {486-499}, pmid = {32431731}, issn = {1752-4571}, abstract = {Biological invasions represent grave threats to terrestrial, aquatic, and marine ecosystems, but our understanding of the role of evolution during invasions remains rudimentary. In marine environments, macroalgae account for a large percentage of invaders, but their complicated life cycles render it difficult to move methodologies and predictions wholesale from species with a single, free-living ploidy stage, such as plants or animals. In haplodiplontic macroalgae, meiosis and fertilization are spatiotemporally separated by long-lived, multicellular haploid and diploid stages, and gametes are produced by mitosis, not meiosis. As a consequence, there are unique eco-evolutionary constraints that are not typically considered in invasions. First, selfing can occur in both monoicious (i.e., hermaphroditic) and dioicious (i.e., separate sexes) haplodiplontic macroalgae. In the former, fertilization between gametes produced by the same haploid thallus results in instantaneous, genome-wide homozygosity. In the latter, cross-fertilization between separate male and female haploids that share the same diploid parent is analogous to selfing in plants or animals. Separate sexes, therefore, cannot be used as a proxy for outcrossing. Second, selfing likely facilitates invasions (i.e., Baker's law) and the long-lived haploid stage may enable purging of deleterious mutations, further contributing to invasion success. Third, asexual reproduction will result in the dominance of one ploidy and/or sex and the loss of the other(s). Whether or not sexual reproduction can be recovered depends on which stage is maintained. Finally, fourth, haplodiplontic life cycles are predicted to be maintained through niche differentiation in the haploid and diploid stages. Empirical tests are rare, but fundamental to our understanding of macroalgal invasion dynamics. By highlighting these four phenomena, we can build a framework with which to empirically and theoretically address important gaps in the literature on marine evolutionary ecology, of which biological invasions can serve as unnatural laboratories.}, } @article {pmid32428501, year = {2020}, author = {Arendt, D}, title = {The Evolutionary Assembly of Neuronal Machinery.}, journal = {Current biology : CB}, volume = {30}, number = {10}, pages = {R603-R616}, doi = {10.1016/j.cub.2020.04.008}, pmid = {32428501}, issn = {1879-0445}, mesh = {Animals ; *Biological Evolution ; Neurons/*physiology ; Synapses/physiology ; Synaptic Transmission/*physiology ; }, abstract = {Neurons are highly specialized cells equipped with a sophisticated molecular machinery for the reception, integration, conduction and distribution of information. The evolutionary origin of neurons remains unsolved. How did novel and pre-existing proteins assemble into the complex machinery of the synapse and of the apparatus conducting current along the neuron? In this review, the step-wise assembly of functional modules in neuron evolution serves as a paradigm for the emergence and modification of molecular machinery in the evolution of cell types in multicellular organisms. The pre-synaptic machinery emerged through modification of calcium-regulated large vesicle release, while the postsynaptic machinery has different origins: the glutamatergic postsynapse originated through the fusion of a sensory signaling module and a module for filopodial outgrowth, while the GABAergic postsynapse incorporated an ancient actin regulatory module. The synaptic junction, in turn, is built around two adhesion modules controlled by phosphorylation, which resemble septate and adherens junctions. Finally, neuronal action potentials emerged via a series of duplications and modifications of voltage-gated ion channels. Based on these origins, key molecular innovations are identified that led to the birth of the first neuron in animal evolution.}, } @article {pmid32421773, year = {2020}, author = {Tollis, M and Schneider-Utaka, AK and Maley, CC}, title = {The Evolution of Human Cancer Gene Duplications across Mammals.}, journal = {Molecular biology and evolution}, volume = {37}, number = {10}, pages = {2875-2886}, pmid = {32421773}, issn = {1537-1719}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA149566/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Dosage ; *Gene Duplication ; *Genes, Neoplasm ; Humans ; *Life History Traits ; Longevity ; Mammals/*genetics ; Mole Rats/genetics ; }, abstract = {Cancer is caused by genetic alterations that affect cellular fitness, and multicellular organisms have evolved mechanisms to suppress cancer such as cell cycle checkpoints and apoptosis. These pathways may be enhanced by the addition of tumor suppressor gene paralogs or deletion of oncogenes. To provide insights to the evolution of cancer suppression across the mammalian radiation, we estimated copy numbers for 548 human tumor suppressor gene and oncogene homologs in 63 mammalian genome assemblies. The naked mole rat contained the most cancer gene copies, consistent with the extremely low rates of cancer found in this species. We found a positive correlation between a species' cancer gene copy number and its longevity, but not body size, contrary to predictions from Peto's Paradox. Extremely long-lived mammals also contained more copies of caretaker genes in their genomes, suggesting that the maintenance of genome integrity is an essential form of cancer prevention in long-lived species. We found the strongest association between longevity and copy numbers of genes that are both germline and somatic tumor suppressor genes, suggesting that selection has acted to suppress both hereditary and sporadic cancers. We also found a strong relationship between the number of tumor suppressor genes and the number of oncogenes in mammalian genomes, suggesting that complex regulatory networks mediate the balance between cell proliferation and checks on tumor progression. This study is the first to investigate cancer gene expansions across the mammalian radiation and provides a springboard for potential human therapies based on evolutionary medicine.}, } @article {pmid32419346, year = {2021}, author = {Guzmán-Herrera, A and Arias Del Angel, JA and Rivera-Yoshida, N and Benítez, M and Franci, A}, title = {Dynamical patterning modules and network motifs as joint determinants of development: Lessons from an aggregative bacterium.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {336}, number = {3}, pages = {300-314}, doi = {10.1002/jez.b.22946}, pmid = {32419346}, issn = {1552-5015}, mesh = {*Biological Evolution ; Body Patterning ; Morphogenesis ; Myxococcus xanthus/*growth & development ; }, abstract = {Development and evolution are dynamical processes under the continuous control of organismic and environmental factors. Generic physical processes, associated with biological materials and certain genes or molecules, provide a morphological template for the evolution and development of organism forms. Generic dynamical behaviors, associated with recurring network motifs, provide a temporal template for the regulation and coordination of biological processes. The role of generic physical processes and their associated molecules in development is the topic of the dynamical patterning module (DPM) framework. The role of generic dynamical behaviors in biological regulation is studied via the identification of the associated network motifs (NMs). We propose a joint DPM-NM perspective on the emergence and regulation of multicellularity focusing on a multicellular aggregative bacterium, Myxococcus xanthus. Understanding M. xanthus development as a dynamical process embedded in a physical substrate provides novel insights into the interaction between developmental regulatory networks and generic physical processes in the evolutionary transition to multicellularity.}, } @article {pmid32415185, year = {2020}, author = {Hörandl, E and Hadacek, F}, title = {Oxygen, life forms, and the evolution of sexes in multicellular eukaryotes.}, journal = {Heredity}, volume = {125}, number = {1-2}, pages = {1-14}, pmid = {32415185}, issn = {1365-2540}, mesh = {Animals ; *Biological Evolution ; *Eukaryota ; Female ; Fungi/genetics ; Male ; Oxidative Stress ; *Oxygen ; Reproduction ; Sex Chromosomes ; Sexual Behavior, Animal ; }, abstract = {The evolutionary advantage of different sexual systems in multicellular eukaryotes is still not well understood, because the differentiation into male and female individuals halves offspring production compared with asexuality. Here we propose that various physiological adaptations to oxidative stress could have forged sessility versus motility, and consequently the evolution of sexual systems in multicellular animals, plants, and fungi. Photosynthesis causes substantial amounts of oxidative stress in photoautotrophic plants and, likewise, oxidative chemistry of polymer breakdown, cellulose and lignin, for saprotrophic fungi. In both cases, its extent precludes motility, an additional source of oxidative stress. Sessile life form and the lack of neuronal systems, however, limit options for mate recognition and adult sexual selection, resulting in inefficient mate-searching systems. Hence, sessility requires that all individuals can produce offspring, which is achieved by hermaphroditism in plants and/or by multiple mating types in fungi. In animals, motility requires neuronal systems, and muscle activity, both of which are highly sensitive to oxidative damage. As a consequence, motility has evolved in animals as heterotrophic organisms that (1) are not photosynthetically active, and (2) are not primary decomposers. Adaptations to motility provide prerequisites for an active mating behavior and efficient mate-searching systems. These benefits compensate for the "cost of males", and may explain the early evolution of sex chromosomes in metazoans. We conclude that different sexual systems evolved under the indirect physiological constraints of lifestyles.}, } @article {pmid32413288, year = {2020}, author = {Okamoto, K and Ferreira, RJ and Larsson, DSD and Maia, FRNC and Isawa, H and Sawabe, K and Murata, K and Hajdu, J and Iwasaki, K and Kasson, PM and Miyazaki, N}, title = {Acquired Functional Capsid Structures in Metazoan Totivirus-like dsRNA Virus.}, journal = {Structure (London, England : 1993)}, volume = {28}, number = {8}, pages = {888-896.e3}, doi = {10.1016/j.str.2020.04.016}, pmid = {32413288}, issn = {1878-4186}, mesh = {Capsid/*chemistry/metabolism ; Cryoelectron Microscopy ; Molecular Dynamics Simulation ; RNA, Double-Stranded/*chemistry/genetics ; RNA, Viral/*chemistry/genetics ; Totivirus/*chemistry/physiology ; Virus Internalization ; Virus Replication ; }, abstract = {Non-enveloped icosahedral double-stranded RNA (dsRNA) viruses possess multifunctional capsids required for their proliferation. Whereas protozoan/fungal dsRNA viruses have a relatively simple capsid structure, which suffices for the intracellular phase in their life cycle, metazoan dsRNA viruses have acquired additional structural features as an adaptation for extracellular cell-to-cell transmission in multicellular hosts. Here, we present the first atomic model of a metazoan dsRNA totivirus-like virus and the structure reveals three unique structural traits: a C-terminal interlocking arm, surface projecting loops, and an obstruction at the pore on the 5-fold symmetry axis. These traits are keys to understanding the capsid functions of metazoan dsRNA viruses, such as particle stability and formation, cell entry, and endogenous intraparticle transcription of mRNA. On the basis of molecular dynamics simulations of the obstructed pore, we propose a possible mechanism of intraparticle transcription in totivirus-like viruses, which dynamically switches between open and closed states of the pore(s).}, } @article {pmid32411685, year = {2020}, author = {Yuan, F and Pan, X and Zeng, T and Zhang, YH and Chen, L and Gan, Z and Huang, T and Cai, YD}, title = {Identifying Cell-Type Specific Genes and Expression Rules Based on Single-Cell Transcriptomic Atlas Data.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {8}, number = {}, pages = {350}, pmid = {32411685}, issn = {2296-4185}, abstract = {Single-cell sequencing technologies have emerged to address new and longstanding biological and biomedical questions. Previous studies focused on the analysis of bulk tissue samples composed of millions of cells. However, the genomes within the cells of an individual multicellular organism are not always the same. In this study, we aimed to identify the crucial and characteristically expressed genes that may play functional roles in tissue development and organogenesis, by analyzing a single-cell transcriptomic atlas of mice. We identified the most relevant gene features and decision rules classifying 18 cell categories, providing a list of genes that may perform important functions in the process of tissue development because of their tissue-specific expression patterns. These genes may serve as biomarkers to identify the origin of unknown cell subgroups so as to recognize specific cell stages/states during the dynamic process, and also be applied as potential therapy targets for developmental disorders.}, } @article {pmid32399193, year = {2020}, author = {Zardoya, R}, title = {Recent advances in understanding mitochondrial genome diversity.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {}, pmid = {32399193}, issn = {2046-1402}, mesh = {Animals ; *Evolution, Molecular ; Fungi/genetics ; *Genome, Mitochondrial ; Introns ; Mitochondria ; Plants/genetics ; RNA Editing ; }, abstract = {Ever since its discovery, the double-stranded DNA contained in the mitochondria of eukaryotes has fascinated researchers because of its bacterial endosymbiotic origin, crucial role in encoding subunits of the respiratory complexes, compact nature, and specific inheritance mechanisms. In the last few years, high-throughput sequencing techniques have accelerated the sequencing of mitochondrial genomes (mitogenomes) and uncovered the great diversity of organizations, gene contents, and modes of replication and transcription found in living eukaryotes. Some early divergent lineages of unicellular eukaryotes retain certain synteny and gene content resembling those observed in the genomes of alphaproteobacteria (the inferred closest living group of mitochondria), whereas others adapted to anaerobic environments have drastically reduced or even lost the mitogenome. In the three main multicellular lineages of eukaryotes, mitogenomes have pursued diverse evolutionary trajectories in which different types of molecules (circular versus linear and single versus multipartite), gene structures (with or without self-splicing introns), gene contents, gene orders, genetic codes, and transfer RNA editing mechanisms have been selected. Whereas animals have evolved a rather compact mitochondrial genome between 11 and 50 Kb in length with a highly conserved gene content in bilaterians, plants exhibit large mitochondrial genomes of 66 Kb to 11.3 Mb with large intergenic repetitions prone to recombination, and fungal mitogenomes have intermediate sizes of 12 to 236 Kb.}, } @article {pmid32393866, year = {2020}, author = {Yu, L and Boström, C and Franzenburg, S and Bayer, T and Dagan, T and Reusch, TBH}, title = {Somatic genetic drift and multilevel selection in a clonal seagrass.}, journal = {Nature ecology & evolution}, volume = {4}, number = {7}, pages = {952-962}, pmid = {32393866}, issn = {2397-334X}, mesh = {*Genetic Drift ; *Genetics, Population ; Reproduction ; }, abstract = {All multicellular organisms are genetic mosaics owing to somatic mutations. The accumulation of somatic genetic variation in clonal species undergoing asexual (or clonal) reproduction may lead to phenotypic heterogeneity among autonomous modules (termed ramets). However, the abundance and dynamics of somatic genetic variation under clonal reproduction remain poorly understood. Here we show that branching events in a seagrass (Zostera marina) clone or genet lead to population bottlenecks of tissue that result in the evolution of genetically differentiated ramets in a process of somatic genetic drift. By studying inter-ramet somatic genetic variation, we uncovered thousands of single nucleotide polymorphisms that segregated among ramets. Ultra-deep resequencing of single ramets revealed that the strength of purifying selection on mosaic genetic variation was greater within than among ramets. Our study provides evidence for multiple levels of selection during the evolution of seagrass genets. Somatic genetic drift during clonal propagation leads to the emergence of genetically unique modules that constitute an elementary level of selection and individuality in long-lived clonal species.}, } @article {pmid32383482, year = {2020}, author = {Kimata, Y and Leturcq, M and Aradhya, R}, title = {Emerging roles of metazoan cell cycle regulators as coordinators of the cell cycle and differentiation.}, journal = {FEBS letters}, volume = {}, number = {}, pages = {}, doi = {10.1002/1873-3468.13805}, pmid = {32383482}, issn = {1873-3468}, support = {2018F0202-000-06//ShanghaiTech University startup grant/ ; }, abstract = {In multicellular organisms, cell proliferation must be tightly coordinated with other developmental processes to form functional tissues and organs. Despite significant advances in our understanding of how the cell cycle is controlled by conserved cell-cycle regulators (CCRs), how the cell cycle is coordinated with cell differentiation in metazoan organisms and how CCRs contribute to this process remain poorly understood. Here, we review the emerging roles of metazoan CCRs as intracellular proliferation-differentiation coordinators in multicellular organisms. We illustrate how major CCRs regulate cellular events that are required for cell fate acquisition and subsequent differentiation. To this end, CCRs employ diverse mechanisms, some of which are separable from those underpinning the conventional cell-cycle-regulatory functions of CCRs. By controlling cell-type-specific specification/differentiation processes alongside the progression of the cell cycle, CCRs enable spatiotemporal coupling between differentiation and cell proliferation in various developmental contexts in vivo. We discuss the significance and implications of this underappreciated role of metazoan CCRs for development, disease and evolution.}, } @article {pmid32355003, year = {2020}, author = {Lazzaro, BP and Zasloff, M and Rolff, J}, title = {Antimicrobial peptides: Application informed by evolution.}, journal = {Science (New York, N.Y.)}, volume = {368}, number = {6490}, pages = {}, pmid = {32355003}, issn = {1095-9203}, support = {R01 AI141385/AI/NIAID NIH HHS/United States ; /ERC_/European Research Council/International ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Antimicrobial Cationic Peptides/chemistry/*genetics/*pharmacology ; Drosophila Proteins/genetics/pharmacology ; *Drug Resistance, Bacterial ; Drug Synergism ; *Evolution, Molecular ; Humans ; Polymorphism, Genetic ; Translational Research, Biomedical ; }, abstract = {Antimicrobial peptides (AMPs) are essential components of immune defenses of multicellular organisms and are currently in development as anti-infective drugs. AMPs have been classically assumed to have broad-spectrum activity and simple kinetics, but recent evidence suggests an unexpected degree of specificity and a high capacity for synergies. Deeper evaluation of the molecular evolution and population genetics of AMP genes reveals more evidence for adaptive maintenance of polymorphism in AMP genes than has previously been appreciated, as well as adaptive loss of AMP activity. AMPs exhibit pharmacodynamic properties that reduce the evolution of resistance in target microbes, and AMPs may synergize with one another and with conventional antibiotics. Both of these properties make AMPs attractive for translational applications. However, if AMPs are to be used clinically, it is crucial to understand their natural biology in order to lessen the risk of collateral harm and avoid the crisis of resistance now facing conventional antibiotics.}, } @article {pmid32353148, year = {2020}, author = {Hoffman, SK and Seitz, KW and Havird, JC and Weese, DA and Santos, SR}, title = {Phenotypic Comparability from Genotypic Variability among Physically Structured Microbial Consortia.}, journal = {Integrative and comparative biology}, volume = {60}, number = {2}, pages = {288-303}, doi = {10.1093/icb/icaa022}, pmid = {32353148}, issn = {1557-7023}, mesh = {Bacteria/*genetics ; Cyanobacteria/genetics ; *Genotype ; Hawaii ; Microbial Consortia/*genetics ; *Phenotype ; }, abstract = {Microbiomes represent the collective bacteria, archaea, protist, fungi, and virus communities living in or on individual organisms that are typically multicellular eukaryotes. Such consortia have become recognized as having significant impacts on the development, health, and disease status of their hosts. Since understanding the mechanistic connections between an individual's genetic makeup and their complete set of traits (i.e., genome to phenome) requires consideration at different levels of biological organization, this should include interactions with, and the organization of, microbial consortia. To understand microbial consortia organization, we elucidated the genetic constituents among phenotypically similar (and hypothesized functionally-analogous) layers (i.e., top orange, second orange, pink, and green layers) in the unique laminated orange cyanobacterial-bacterial crusts endemic to Hawaii's anchialine ecosystem. High-throughput amplicon sequencing of ribosomal RNA hypervariable regions (i.e., Bacteria-specific V6 and Eukarya-biased V9) revealed microbial richness increasing by crust layer depth, with samples of a given layer more similar to different layers from the same geographic site than to their phenotypically-analogous layer from different sites. Furthermore, samples from sites on the same island were more similar to each other, regardless of which layer they originated from, than to analogous layers from another island. However, cyanobacterial and algal taxa were abundant in all surface and bottom layers, with anaerobic and chemoautotrophic taxa concentrated in the middle two layers, suggesting crust oxygenation from both above and below. Thus, the arrangement of oxygenated vs. anoxygenated niches in these orange crusts is functionally distinct relative to other laminated cyanobacterial-bacterial communities examined to date, with convergent evolution due to similar environmental conditions a likely driver for these phenotypically comparable but genetically distinct microbial consortia.}, } @article {pmid32330159, year = {2020}, author = {Safdari, H and Kalirad, A and Picioreanu, C and Tusserkani, R and Goliaei, B and Sadeghi, M}, title = {Noise-driven cell differentiation and the emergence of spatiotemporal patterns.}, journal = {PloS one}, volume = {15}, number = {4}, pages = {e0232060}, pmid = {32330159}, issn = {1932-6203}, mesh = {Adaptation, Biological/*physiology ; Animals ; Artifacts ; *Biodiversity ; *Biological Evolution ; Cell Differentiation/physiology ; Cell Lineage/physiology ; Humans ; Models, Biological ; Models, Theoretical ; Phenotype ; Spatio-Temporal Analysis ; }, abstract = {The emergence of phenotypic diversity in a population of cells and their arrangement in space and time is one of the most fascinating features of living systems. In fact, understanding multicellularity is unthinkable without explaining the proximate and the ultimate causes of cell differentiation in time and space. Simpler forms of cell differentiation can be found in unicellular organisms, such as bacterial biofilm, where reversible cell differentiation results in phenotypically diverse populations. In this manuscript, we attempt to start with the simple case of reversible nongenetic phenotypic to construct a model of differentiation and pattern formation. Our model, which we refer to as noise-driven differentiation (NDD) model, is an attempt to consider the prevalence of noise in biological systems, alongside what is known about genetic switches and signaling, to create a simple model which generates spatiotemporal patterns from bottom-up. Our simulations indicate that the presence of noise in cells can lead to reversible differentiation and the addition of signaling can create spatiotemporal pattern.}, } @article {pmid32315081, year = {2020}, author = {Rainey, L and Deevi, RK and McClements, J and Khawaja, H and Watson, CJ and Roudier, M and Van Schaeybroeck, S and Campbell, FC}, title = {Fundamental control of grade-specific colorectal cancer morphology by Src regulation of ezrin-centrosome engagement.}, journal = {The Journal of pathology}, volume = {251}, number = {3}, pages = {310-322}, doi = {10.1002/path.5452}, pmid = {32315081}, issn = {1096-9896}, support = {MR/L015110/1/MRC_/Medical Research Council/United Kingdom ; L015110/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Caco-2 Cells ; Centrosome/*enzymology/pathology ; Colorectal Neoplasms/*enzymology/genetics/pathology ; Cytoskeletal Proteins/genetics/*metabolism ; Focal Adhesion Kinase 1/genetics/metabolism ; HCT116 Cells ; Humans ; *Mitosis ; Neoplasm Grading ; PTEN Phosphohydrolase/genetics/metabolism ; Signal Transduction ; src-Family Kinases/genetics/*metabolism ; }, abstract = {The phenotypic spectrum of colorectal cancer (CRC) is remarkably diverse, with seemingly endless variations in cell shape, mitotic figures and multicellular configurations. Despite this morphological complexity, histological grading of collective phenotype patterns provides robust prognostic stratification in CRC. Although mechanistic understanding is incomplete, previous studies have shown that the cortical protein ezrin controls diversification of cell shape, mitotic figure geometry and multicellular architecture, in 3D organotypic CRC cultures. Because ezrin is a substrate of Src tyrosine kinase that is frequently overexpressed in CRC, we investigated Src regulation of ezrin and morphogenic growth in 3D CRC cultures. Here we show that Src perturbations disrupt CRC epithelial spatial organisation. Aberrant Src activity suppresses formation of the cortical ezrin cap that anchors interphase centrosomes. In CRC cells with a normal centrosome number, these events lead to mitotic spindle misorientation, perturbation of cell cleavage, abnormal epithelial stratification, apical membrane misalignment, multilumen formation and evolution of cribriform multicellular morphology, a feature of low-grade cancer. In isogenic CRC cells with centrosome amplification, aberrant Src signalling promotes multipolar mitotic spindle formation, pleomorphism and morphological features of high-grade cancer. Translational studies in archival human CRC revealed associations between Src intensity, multipolar mitotic spindle frequency and high-grade cancer morphology. Collectively, our study reveals Src regulation of CRC morphogenic growth via ezrin-centrosome engagement and uncovers combined perturbations underlying transition to high-grade CRC morphology. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.}, } @article {pmid32305342, year = {2020}, author = {Friedman, DA and Johnson, BR and Linksvayer, TA}, title = {Distributed physiology and the molecular basis of social life in eusocial insects.}, journal = {Hormones and behavior}, volume = {122}, number = {}, pages = {104757}, doi = {10.1016/j.yhbeh.2020.104757}, pmid = {32305342}, issn = {1095-6867}, mesh = {Animals ; Ants/genetics/physiology ; Bees/genetics/physiology ; Behavior, Animal/*physiology ; Biological Evolution ; Cooperative Behavior ; Genome, Insect/*physiology ; Insecta/*genetics/*physiology ; Isoptera/genetics/physiology ; Nesting Behavior/physiology ; Phenotype ; *Social Behavior ; }, abstract = {The traditional focus of physiological and functional genomic research is on molecular processes that play out within a single multicellular organism. In the colonial (eusocial) insects such as ants, bees, and termites, molecular and behavioral responses of interacting nestmates are tightly linked, and key physiological processes are regulated at the scale of the colony. Such colony-level physiological processes regulate nestmate physiology in a distributed fashion, through various social communication mechanisms. As a result of physiological decentralization over evolutionary time, organismal mechanisms, for example related to pheromone detection, hormone signaling, and neural signaling pathways, are deployed in novel contexts to influence nestmate and colony traits. Here we explore how functional genomic, physiological, and behavioral studies can benefit from considering the traits of eusocial insects in this light. We highlight functional genomic work exploring how nestmate-level and colony-level traits arise and are influenced by interactions among physiologically-specialized nestmates of various developmental stages. We also consider similarities and differences between nestmate-level (organismal) and colony-level (superorganismal) physiological processes, and make specific hypotheses regarding the physiology of eusocial taxa. Integrating theoretical models of distributed systems with empirical functional genomics approaches will be useful in addressing fundamental questions related to the evolution of eusociality and collective behavior in natural systems.}, } @article {pmid32301582, year = {2020}, author = {Naranjo-Ortiz, MA and Gabaldón, T}, title = {Fungal evolution: cellular, genomic and metabolic complexity.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {95}, number = {5}, pages = {1198-1232}, pmid = {32301582}, issn = {1469-185X}, support = {PT17/0009/0023 - ISCIII-SGEFI/ERDF//INB Grant/International ; H2020-MSCA-IF-2017-793699//Marie Sklodowska-Curie/International ; ERC-2016-724173//European Union's Horizon 2020/International ; SGR423//Catalan Research Agency (AGAUR)/International ; //CERCA Programme/Generalitat de Catalunya/International ; //European Regional Development Fund/International ; //Spanish Ministry of Science and Innovation/International ; }, mesh = {Adaptation, Physiological ; Animals ; *Fungi/genetics ; *Genome, Fungal ; Genomics ; Plants/genetics ; }, abstract = {The question of how phenotypic and genomic complexity are inter-related and how they are shaped through evolution is a central question in biology that historically has been approached from the perspective of animals and plants. In recent years, however, fungi have emerged as a promising alternative system to address such questions. Key to their ecological success, fungi present a broad and diverse range of phenotypic traits. Fungal cells can adopt many different shapes, often within a single species, providing them with great adaptive potential. Fungal cellular organizations span from unicellular forms to complex, macroscopic multicellularity, with multiple transitions to higher or lower levels of cellular complexity occurring throughout the evolutionary history of fungi. Similarly, fungal genomes are very diverse in their architecture. Deep changes in genome organization can occur very quickly, and these phenomena are known to mediate rapid adaptations to environmental changes. Finally, the biochemical complexity of fungi is huge, particularly with regard to their secondary metabolites, chemical products that mediate many aspects of fungal biology, including ecological interactions. Herein, we explore how the interplay of these cellular, genomic and metabolic traits mediates the emergence of complex phenotypes, and how this complexity is shaped throughout the evolutionary history of Fungi.}, } @article {pmid32290841, year = {2020}, author = {Gao, F and Cai, Y and Kapranov, P and Xu, D}, title = {Reverse-genetics studies of lncRNAs-what we have learnt and paths forward.}, journal = {Genome biology}, volume = {21}, number = {1}, pages = {93}, pmid = {32290841}, issn = {1474-760X}, mesh = {Animals ; Evolution, Molecular ; Phenotype ; RNA, Long Noncoding/*physiology ; Reverse Genetics ; Vertebrates/genetics ; }, abstract = {Long non-coding RNAs (lncRNAs) represent a major fraction of the transcriptome in multicellular organisms. Although a handful of well-studied lncRNAs are broadly recognized as biologically meaningful, the fraction of such transcripts out of the entire collection of lncRNAs remains a subject of vigorous debate. Here we review the evidence for and against biological functionalities of lncRNAs and attempt to arrive at potential modes of lncRNA functionality that would reconcile the contradictory conclusions. Finally, we discuss different strategies of phenotypic analyses that could be used to investigate such modes of lncRNA functionality.}, } @article {pmid32286494, year = {2020}, author = {Masuda, T and Inomura, K and Takahata, N and Shiozaki, T and Sano, Y and Deutsch, C and Prášil, O and Furuya, K}, title = {Heterogeneous nitrogen fixation rates confer energetic advantage and expanded ecological niche of unicellular diazotroph populations.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {172}, pmid = {32286494}, issn = {2399-3642}, mesh = {Adaptation, Physiological ; *Biological Evolution ; Computer Simulation ; Cyanobacteria/growth & development/*metabolism ; Cyanothece/growth & development/*metabolism ; Ecosystem ; *Energy Metabolism ; Models, Biological ; Nitrogen/*metabolism ; *Nitrogen Fixation ; }, abstract = {Nitrogen fixing plankton provide nitrogen to fuel marine ecosystems and biogeochemical cycles but the factors that constrain their growth and habitat remain poorly understood. Here we investigate the importance of metabolic specialization in unicellular diazotroph populations, using laboratory experiments and model simulations. In clonal cultures of Crocosphaera watsonii and Cyanothece sp. spiked with [15]N2, cellular [15]N enrichment developed a bimodal distribution within colonies, indicating that N2 fixation was confined to a subpopulation. In a model of population metabolism, heterogeneous nitrogen (N2) fixation rates substantially reduce the respiration rate required to protect nitrogenase from O2. The energy savings from metabolic specialization is highest at slow growth rates, allowing populations to survive in deeper waters where light is low but nutrients are high. Our results suggest that heterogeneous N2 fixation in colonies of unicellular diazotrophs confers an energetic advantage that expands the ecological niche and may have facilitated the evolution of multicellular diazotrophs.}, } @article {pmid32285363, year = {2020}, author = {Low, LA and Sutherland, M and Lumelsky, N and Selimovic, S and Lundberg, MS and Tagle, DA}, title = {Organs-on-a-Chip.}, journal = {Advances in experimental medicine and biology}, volume = {1230}, number = {}, pages = {27-42}, doi = {10.1007/978-3-030-36588-2_3}, pmid = {32285363}, issn = {0065-2598}, mesh = {Animals ; Drug Development ; Drug Discovery ; Humans ; *Lab-On-A-Chip Devices ; *Tissue Array Analysis ; }, abstract = {Organs-on-chips, also known as "tissue chips" or microphysiological systems (MPS), are bioengineered microsystems capable of recreating aspects of human organ physiology and function and are in vitro tools with multiple applications in drug discovery and development. The ability to recapitulate human and animal tissues in physiologically relevant three-dimensional, multi-cellular environments allows applications in the drug development field, including; (1) use in assessing the safety and toxicity testing of potential therapeutics during early-stage preclinical drug development; (2) confirmation of drug/therapeutic efficacy in vitro; and (3) disease modeling of human tissues to recapitulate pathophysiology within specific subpopulations and even individuals, thereby advancing precision medicine efforts. This chapter will discuss the development and evolution of three-dimensional organ models over the past decade, and some of the opportunities offered by MPS technology that are not available through current standard two-dimensional cell cultures, or three-dimensional organoid systems. This chapter will outline future avenues of research in the MPS field, how cutting-edge biotechnology advances are expanding the applications for these systems, and discuss the current and future potential and challenges remaining for the field to address.}, } @article {pmid32284424, year = {2020}, author = {Fouchard, J and Wyatt, TPJ and Proag, A and Lisica, A and Khalilgharibi, N and Recho, P and Suzanne, M and Kabla, A and Charras, G}, title = {Curling of epithelial monolayers reveals coupling between active bending and tissue tension.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {17}, pages = {9377-9383}, pmid = {32284424}, issn = {1091-6490}, support = {BB/M003280/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M002578/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Biomechanical Phenomena ; Cell Adhesion ; Cell Line ; Dogs ; Elasticity ; Epithelium/*physiology ; Stress, Mechanical ; }, abstract = {Epithelial monolayers are two-dimensional cell sheets which compartmentalize the body and organs of multicellular organisms. Their morphogenesis during development or pathology results from patterned endogenous and exogenous forces and their interplay with tissue mechanical properties. In particular, bending of epithelia is thought to result from active torques generated by the polarization of myosin motors along their apicobasal axis. However, the contribution of these out-of-plane forces to morphogenesis remains challenging to evaluate because of the lack of direct mechanical measurement. Here we use epithelial curling to characterize the out-of-plane mechanics of epithelial monolayers. We find that curls of high curvature form spontaneously at the free edge of epithelial monolayers devoid of substrate in vivo and in vitro. Curling originates from an enrichment of myosin in the basal domain that generates an active spontaneous curvature. By measuring the force necessary to flatten curls, we can then estimate the active torques and the bending modulus of the tissue. Finally, we show that the extent of curling is controlled by the interplay between in-plane and out-of-plane stresses in the monolayer. Such mechanical coupling emphasizes a possible role for in-plane stresses in shaping epithelia during morphogenesis.}, } @article {pmid32283732, year = {2020}, author = {Annenkova, NV and Giner, CR and Logares, R}, title = {Tracing the Origin of Planktonic Protists in an Ancient Lake.}, journal = {Microorganisms}, volume = {8}, number = {4}, pages = {}, pmid = {32283732}, issn = {2076-2607}, support = {18-74-00054//Russian Science Foundation/ ; 0345-2016-0009//Russian state assignment/ ; RYC-2013-12554//Ministerio de Economía y Competitividad/ ; }, abstract = {Ancient lakes are among the most interesting models for evolution studies because their biodiversity is the result of a complex combination of migration and speciation. Here, we investigate the origin of single celled planktonic eukaryotes from the oldest lake in the world-Lake Baikal (Russia). By using 18S rDNA metabarcoding, we recovered 1414 Operational Taxonomic Units (OTUs) belonging to protists populating surface waters (1-50 m) and representing pico/nano-sized cells. The recovered communities resembled other lacustrine freshwater assemblages found elsewhere, especially the taxonomically unclassified protists. However, our results suggest that a fraction of Baikal protists could belong to glacial relicts and have close relationships with marine/brackish species. Moreover, our results suggest that rapid radiation may have occurred among some protist taxa, partially mirroring what was already shown for multicellular organisms in Lake Baikal. We found 16% of the OTUs belonging to potential species flocks in Stramenopiles, Alveolata, Opisthokonta, Archaeplastida, Rhizaria, and Hacrobia. Putative flocks predominated in Chrysophytes, which are highly diverse in Lake Baikal. Also, the 18S rDNA of a number of species (7% of the total) differed >10% from other known sequences. These taxa as well as those belonging to the flocks may be endemic to Lake Baikal. Overall, our study points to novel diversity of planktonic protists in Lake Baikal, some of which may have emerged in situ after evolutionary diversification.}, } @article {pmid32282832, year = {2020}, author = {Brun-Usan, M and Thies, C and Watson, RA}, title = {How to fit in: The learning principles of cell differentiation.}, journal = {PLoS computational biology}, volume = {16}, number = {4}, pages = {e1006811}, pmid = {32282832}, issn = {1553-7358}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Biological Evolution ; *Cell Differentiation ; Computer Simulation ; Developmental Biology/*methods ; Environment ; Gene Regulatory Networks ; Genetic Variation ; Learning ; Models, Biological ; Phenotype ; Selection, Genetic ; }, abstract = {Cell differentiation in multicellular organisms requires cells to respond to complex combinations of extracellular cues, such as morphogen concentrations. Some models of phenotypic plasticity conceptualise the response as a relatively simple function of a single environmental cues (e.g. a linear function of one cue), which facilitates rigorous analysis. Conversely, more mechanistic models such those implementing GRNs allows for a more general class of response functions but makes analysis more difficult. Therefore, a general theory describing how cells integrate multi-dimensional signals is lacking. In this work, we propose a theoretical framework for understanding the relationships between environmental cues (inputs) and phenotypic responses (outputs) underlying cell plasticity. We describe the relationship between environment and cell phenotype using logical functions, making the evolution of cell plasticity equivalent to a simple categorisation learning task. This abstraction allows us to apply principles derived from learning theory to understand the evolution of multi-dimensional plasticity. Our results show that natural selection is capable of discovering adaptive forms of cell plasticity associated with complex logical functions. However, developmental dynamics cause simpler functions to evolve more readily than complex ones. By using conceptual tools derived from learning theory we show that this developmental bias can be interpreted as a learning bias in the acquisition of plasticity functions. Because of that bias, the evolution of plasticity enables cells, under some circumstances, to display appropriate plastic responses to environmental conditions that they have not experienced in their evolutionary past. This is possible when the selective environment mirrors the bias of the developmental dynamics favouring the acquisition of simple plasticity functions-an example of the necessary conditions for generalisation in learning systems. These results illustrate the functional parallelisms between learning in neural networks and the action of natural selection on environmentally sensitive gene regulatory networks. This offers a theoretical framework for the evolution of plastic responses that integrate information from multiple cues, a phenomenon that underpins the evolution of multicellularity and developmental robustness.}, } @article {pmid32278076, year = {2020}, author = {Hehenberger, E and Eitel, M and Fortunato, SAV and Miller, DJ and Keeling, PJ and Cahill, MA}, title = {Early eukaryotic origins and metazoan elaboration of MAPR family proteins.}, journal = {Molecular phylogenetics and evolution}, volume = {148}, number = {}, pages = {106814}, doi = {10.1016/j.ympev.2020.106814}, pmid = {32278076}, issn = {1095-9513}, mesh = {Amino Acid Sequence ; Animals ; Eukaryota/*metabolism ; Evolution, Molecular ; Membrane Proteins/chemistry/*metabolism ; Phylogeny ; Protein Binding ; Protein Domains ; Receptors, Progesterone/chemistry/genetics/*metabolism ; }, abstract = {The membrane-associated progesterone receptor (MAPR) family consists of heme-binding proteins containing a cytochrome b5 (cytb5) domain characterized by the presence of a MAPR-specific interhelical insert region (MIHIR) between helices 3 and 4 of the canonical cytb5-domain fold. Animals possess three MAPR genes (PGRMC-like, Neuferricin and Neudesin). Here we show that all three animal MAPR genes were already present in the common ancestor of the opisthokonts (comprising animals and fungi as well as related single-celled taxa). All three MAPR genes acquired extensions C-terminal to the cytb5 domain, either before or with the evolution of animals. The archetypical MAPR protein, progesterone receptor membrane component 1 (PGRMC1), contains phosphorylated tyrosines Y139 and Y180. The combination of Y139/Y180 appeared in the common ancestor of cnidarians and bilaterians, along with an early embryological organizer and synapsed neurons, and is strongly conserved in all bilaterian animals. A predicted protein interaction motif in the PGRMC1 MIHIR is potentially regulated by Y139 phosphorylation. A multilayered model of animal MAPR function acquisition includes some pre-metazoan functions (e.g., heme binding and cytochrome P450 interactions) and some acquired animal-specific functions that involve regulation of strongly conserved protein interaction motifs acquired by animals (Metazoa). This study provides a conceptual framework for future studies, against which especially PGRMC1's multiple functions can perhaps be stratified and functionally dissected.}, } @article {pmid32272915, year = {2020}, author = {Tikhonenkov, DV and Hehenberger, E and Esaulov, AS and Belyakova, OI and Mazei, YA and Mylnikov, AP and Keeling, PJ}, title = {Insights into the origin of metazoan multicellularity from predatory unicellular relatives of animals.}, journal = {BMC biology}, volume = {18}, number = {1}, pages = {39}, pmid = {32272915}, issn = {1741-7007}, support = {18-14-00239//Russian Science Foundation/International ; 227301//Natural Sciences and Engineering Research Council of Canada (CA)/International ; }, mesh = {Animals ; *Biological Evolution ; Eukaryota/*physiology ; Evolution, Molecular ; Invertebrates/*physiology ; Phylogeny ; Predatory Behavior ; }, abstract = {BACKGROUND: The origin of animals from their unicellular ancestor was one of the most important events in evolutionary history, but the nature and the order of events leading up to the emergence of multicellular animals are still highly uncertain. The diversity and biology of unicellular relatives of animals have strongly informed our understanding of the transition from single-celled organisms to the multicellular Metazoa. Here, we analyze the cellular structures and complex life cycles of the novel unicellular holozoans Pigoraptor and Syssomonas (Opisthokonta), and their implications for the origin of animals.

RESULTS: Syssomonas and Pigoraptor are characterized by complex life cycles with a variety of cell types including flagellates, amoeboflagellates, amoeboid non-flagellar cells, and spherical cysts. The life cycles also include the formation of multicellular aggregations and syncytium-like structures, and an unusual diet for single-celled opisthokonts (partial cell fusion and joint sucking of a large eukaryotic prey), all of which provide new insights into the origin of multicellularity in Metazoa. Several existing models explaining the origin of multicellular animals have been put forward, but these data are interestingly consistent with one, the "synzoospore hypothesis."

CONCLUSIONS: The feeding modes of the ancestral metazoan may have been more complex than previously thought, including not only bacterial prey, but also larger eukaryotic cells and organic structures. The ability to feed on large eukaryotic prey could have been a powerful trigger in the formation and development of both aggregative (e.g., joint feeding, which also implies signaling) and clonal (e.g., hypertrophic growth followed by palintomy) multicellular stages that played important roles in the emergence of multicellular animals.}, } @article {pmid32260425, year = {2020}, author = {Simeone, P and Bologna, G and Lanuti, P and Pierdomenico, L and Guagnano, MT and Pieragostino, D and Del Boccio, P and Vergara, D and Marchisio, M and Miscia, S and Mariani-Costantini, R}, title = {Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers.}, journal = {International journal of molecular sciences}, volume = {21}, number = {7}, pages = {}, pmid = {32260425}, issn = {1422-0067}, mesh = {Biomarkers/*metabolism ; Cell Communication ; Disease/*genetics ; Extracellular Vesicles/genetics/*metabolism ; Genetic Predisposition to Disease ; Humans ; Immunity ; Signal Transduction ; }, abstract = {Extracellular vesicles act as shuttle vectors or signal transducers that can deliver specific biological information and have progressively emerged as key regulators of organized communities of cells within multicellular organisms in health and disease. Here, we survey the evolutionary origin, general characteristics, and biological significance of extracellular vesicles as mediators of intercellular signaling, discuss the various subtypes of extracellular vesicles thus far described and the principal methodological approaches to their study, and review the role of extracellular vesicles in tumorigenesis, immunity, non-synaptic neural communication, vascular-neural communication through the blood-brain barrier, renal pathophysiology, and embryo-fetal/maternal communication through the placenta.}, } @article {pmid32253342, year = {2020}, author = {Urrejola, C and von Dassow, P and van den Engh, G and Salas, L and Mullineaux, CW and Vicuña, R and Sánchez-Baracaldo, P}, title = {Loss of Filamentous Multicellularity in Cyanobacteria: the Extremophile Gloeocapsopsis sp. Strain UTEX B3054 Retained Multicellular Features at the Genomic and Behavioral Levels.}, journal = {Journal of bacteriology}, volume = {202}, number = {12}, pages = {}, pmid = {32253342}, issn = {1098-5530}, mesh = {*Biological Evolution ; Cyanobacteria/classification/*genetics/physiology ; Ecosystem ; Extremophiles/classification/*genetics/physiology ; Genome, Bacterial ; Genomics ; Phylogeny ; }, abstract = {Multicellularity in Cyanobacteria played a key role in their habitat expansion, contributing to the Great Oxidation Event around 2.45 billion to 2.32 billion years ago. Evolutionary studies have indicated that some unicellular cyanobacteria emerged from multicellular ancestors, yet little is known about how the emergence of new unicellular morphotypes from multicellular ancestors occurred. Our results give new insights into the evolutionary reversion from which the Gloeocapsopsis lineage emerged. Flow cytometry and microscopy results revealed morphological plasticity involving the patterned formation of multicellular morphotypes sensitive to environmental stimuli. Genomic analyses unveiled the presence of multicellularity-associated genes in its genome. Calcein-fluorescence recovery after photobleaching (FRAP) experiments confirmed that Gloeocapsopsis sp. strain UTEX B3054 carries out cell-to-cell communication in multicellular morphotypes but at slower time scales than filamentous cyanobacteria. Although traditionally classified as unicellular, our results suggest that Gloeocapsopsis displays facultative multicellularity, a condition that may have conferred ecological advantages for thriving as an extremophile for more than 1.6 billion years.IMPORTANCECyanobacteria are among the few prokaryotes that evolved multicellularity. The early emergence of multicellularity in Cyanobacteria (2.5 billion years ago) entails that some unicellular cyanobacteria reverted from multicellular ancestors. We tested this evolutionary hypothesis by studying the unicellular strain Gloeocapsopsis sp. UTEX B3054 using flow cytometry, genomics, and cell-to-cell communication experiments. We demonstrate the existence of a well-defined patterned organization of cells in clusters during growth, which might change triggered by environmental stimuli. Moreover, we found genomic signatures of multicellularity in the Gloeocapsopsis genome, giving new insights into the evolutionary history of a cyanobacterial lineage that has thrived in extreme environments since the early Earth. The potential benefits in terms of resource acquisition and the ecological relevance of this transient behavior are discussed.}, } @article {pmid32253306, year = {2020}, author = {Shao, S and Koh, M and Schultz, PG}, title = {Expanding the genetic code of the human hematopoietic system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {16}, pages = {8845-8849}, pmid = {32253306}, issn = {1091-6490}, support = {R01 GM132071/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acids/*genetics ; Animals ; Cell Differentiation/*genetics ; Fetal Blood/cytology ; Gene Transfer Techniques ; Genetic Code ; Genetic Vectors/*genetics ; HEK293 Cells ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*physiology ; Herpesvirus 4, Human/genetics ; Humans ; Mice ; Mice, Inbred NOD ; Plasmids/genetics ; Primary Cell Culture/methods ; Protein Engineering/*methods ; Transfection/methods ; Transplantation Chimera ; Transplantation, Heterologous/methods ; }, abstract = {The genetic incorporation of noncanonical amino acids (ncAAs) into proteins has been realized in bacteria, yeast, and mammalian cells, and recently, in multicellular organisms including plants and animals. However, the addition of new building blocks to the genetic code of tissues from human origin has not yet been achieved. To this end, we report a self-replicating Epstein-Barr virus-based episomal vector for the long-term encoding of ncAAs in human hematopoietic stem cells and reconstitution of this genetically engineered hematopoietic system in mice.}, } @article {pmid32251406, year = {2020}, author = {Kazer, SW and Aicher, TP and Muema, DM and Carroll, SL and Ordovas-Montanes, J and Miao, VN and Tu, AA and Ziegler, CGK and Nyquist, SK and Wong, EB and Ismail, N and Dong, M and Moodley, A and Berger, B and Love, JC and Dong, KL and Leslie, A and Ndhlovu, ZM and Ndung'u, T and Walker, BD and Shalek, AK}, title = {Integrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection.}, journal = {Nature medicine}, volume = {26}, number = {4}, pages = {511-518}, pmid = {32251406}, issn = {1546-170X}, support = {UM1 AI100663/AI/NIAID NIH HHS/United States ; 107752/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; R01 AI138546/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; T32 GM087237/GM/NIGMS NIH HHS/United States ; P01 AI039671/AI/NIAID NIH HHS/United States ; R01 AI145305/AI/NIAID NIH HHS/United States ; T32 GM008313/GM/NIGMS NIH HHS/United States ; U19 AI089992/AI/NIAID NIH HHS/United States ; P30 AI060354/AI/NIAID NIH HHS/United States ; RM1 HG006193/HG/NHGRI NIH HHS/United States ; R01 HL095791/HL/NHLBI NIH HHS/United States ; 210662/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; UM1 AI144462/AI/NIAID NIH HHS/United States ; R01 AI118544/AI/NIAID NIH HHS/United States ; R01 HL134539/HL/NHLBI NIH HHS/United States ; K08 AI118538/AI/NIAID NIH HHS/United States ; R37 AI067073/AI/NIAID NIH HHS/United States ; U24 AI118672/AI/NIAID NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; U54 CA217377/CA/NCI NIH HHS/United States ; R01 DA046277/DA/NIDA NIH HHS/United States ; }, mesh = {Acute Disease ; Acute-Phase Reaction/genetics/immunology/pathology ; Adolescent ; Adult ; *Cell Communication/genetics/immunology ; Female ; Gene Expression Profiling ; Gene Regulatory Networks/immunology ; HIV Infections/*genetics/*immunology/pathology ; HIV-1/genetics/pathogenicity ; Humans ; Immunity, Cellular/*physiology ; Killer Cells, Natural/immunology/metabolism ; Leukocytes, Mononuclear/metabolism/pathology ; Longitudinal Studies ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/*methods ; Systems Integration ; T-Lymphocytes, Cytotoxic/immunology/metabolism ; Viral Load/genetics/immunology ; Young Adult ; }, abstract = {Cellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell-cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease[1,2] and nominating testable therapeutic targets[3]. Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability[4]. Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection[5], we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination.}, } @article {pmid32246828, year = {2020}, author = {Zheng, W and Chen, J and Doak, TG and Song, W and Yan, Y}, title = {ADFinder: accurate detection of programmed DNA elimination using NGS high-throughput sequencing data.}, journal = {Bioinformatics (Oxford, England)}, volume = {36}, number = {12}, pages = {3632-3636}, doi = {10.1093/bioinformatics/btaa226}, pmid = {32246828}, issn = {1367-4811}, mesh = {Genome ; *Genomics ; High-Throughput Nucleotide Sequencing ; RNA Splicing ; Sequence Analysis, DNA ; *Software ; }, abstract = {MOTIVATION: Programmed DNA elimination (PDE) plays a crucial role in the transitions between germline and somatic genomes in diverse organisms ranging from unicellular ciliates to multicellular nematodes. However, software specific for the detection of DNA splicing events is scarce. In this paper, we describe Accurate Deletion Finder (ADFinder), an efficient detector of PDEs using high-throughput sequencing data. ADFinder can predict PDEs with relatively low sequencing coverage, detect multiple alternative splicing forms in the same genomic location and calculate the frequency for each splicing event. This software will facilitate research of PDEs and all down-stream analyses.

RESULTS: By analyzing genome-wide DNA splicing events in two micronuclear genomes of Oxytricha trifallax and Tetrahymena thermophila, we prove that ADFinder is effective in predicting large scale PDEs.

The source codes and manual of ADFinder are available in our GitHub website: https://github.com/weibozheng/ADFinder.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid32246068, year = {2020}, author = {Buddingh', BC and Elzinga, J and van Hest, JCM}, title = {Intercellular communication between artificial cells by allosteric amplification of a molecular signal.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {1652}, pmid = {32246068}, issn = {2041-1723}, mesh = {Allosteric Regulation ; *Artificial Cells/chemistry/metabolism ; *Cell Communication ; Synthetic Biology/methods ; }, abstract = {Multicellular organisms rely on intercellular communication to coordinate the behaviour of individual cells, which enables their differentiation and hierarchical organization. Various cell mimics have been developed to establish fundamental engineering principles for the construction of artificial cells displaying cell-like organization, behaviour and complexity. However, collective phenomena, although of great importance for a better understanding of life-like behaviour, are underexplored. Here, we construct collectives of giant vesicles that can communicate with each other through diffusing chemical signals that are recognized and processed by synthetic enzymatic cascades. Similar to biological cells, the Receiver vesicles can transduce a weak signal originating from Sender vesicles into a strong response by virtue of a signal amplification step, which facilitates the propagation of signals over long distances within the artificial cell consortia. This design advances the development of interconnected artificial cells that can exchange metabolic and positional information to coordinate their higher-order organization.}, } @article {pmid32244231, year = {2020}, author = {Copley, SD}, title = {The physical basis and practical consequences of biological promiscuity.}, journal = {Physical biology}, volume = {}, number = {}, pages = {}, pmid = {32244231}, issn = {1478-3975}, support = {R01 GM124365/GM/NIGMS NIH HHS/United States ; R01 GM134044/GM/NIGMS NIH HHS/United States ; }, abstract = {Proteins interact with metabolites, nucleic acids, and other proteins to orchestrate the myriad catalytic, structural and regulatory functions that support life from the simplest microbes to the most complex multicellular organisms. These molecular interactions are often exquisitely specific, but never perfectly so. Adventitious "promiscuous" interactions are ubiquitous due to the thousands of macromolecules and small molecules crowded together in cells. Such interactions may perturb protein function at the molecular level, but as long as they do not compromise organismal fitness, they will not be removed by natural selection. Although promiscuous interactions are physiologically irrelevant, they are important because they can provide a vast reservoir of potential functions that can provide the starting point for evolution of new functions, both in nature and in the laboratory.}, } @article {pmid32234827, year = {2020}, author = {Pienta, KJ and Hammarlund, EU and Axelrod, R and Amend, SR and Brown, JS}, title = {Convergent Evolution, Evolving Evolvability, and the Origins of Lethal Cancer.}, journal = {Molecular cancer research : MCR}, volume = {18}, number = {6}, pages = {801-810}, pmid = {32234827}, issn = {1557-3125}, support = {U01 CA196390/CA/NCI NIH HHS/United States ; U54 CA143803/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; U54 CA143970/CA/NCI NIH HHS/United States ; U54 CA163124/CA/NCI NIH HHS/United States ; P01 CA093900/CA/NCI NIH HHS/United States ; U01 CA143055/CA/NCI NIH HHS/United States ; U54 CA210173/CA/NCI NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; *Genetic Variation ; Humans ; *Mutation ; Neoplasms/*genetics/*pathology ; *Selection, Genetic ; }, abstract = {Advances in curative treatment to remove the primary tumor have increased survival of localized cancers for most solid tumor types, yet cancers that have spread are typically incurable and account for >90% of cancer-related deaths. Metastatic disease remains incurable because, somehow, tumors evolve resistance to all known compounds, including therapies. In all of these incurable patients, de novo lethal cancer evolves capacities for both metastasis and resistance. Therefore, cancers in different patients appear to follow the same eco-evolutionary path that independently manifests in affected patients. This convergent outcome, that always includes the ability to metastasize and exhibit resistance, demands an explanation beyond the slow and steady accrual of stochastic mutations. The common denominator may be that cancer starts as a speciation event when a unicellular protist breaks away from its multicellular host and initiates a cancer clade within the patient. As the cancer cells speciate and diversify further, some evolve the capacity to evolve: evolvability. Evolvability becomes a heritable trait that influences the available variation of other phenotypes that can then be acted upon by natural selection. Evolving evolvability may be an adaptation for cancer cells. By generating and maintaining considerable heritable variation, the cancer clade can, with high certainty, serendipitously produce cells resistant to therapy and cells capable of metastasizing. Understanding that cancer cells can swiftly evolve responses to novel and varied stressors create opportunities for adaptive therapy, double-bind therapies, and extinction therapies; all involving strategic decision making that steers and anticipates the convergent coevolutionary responses of the cancers.}, } @article {pmid32234519, year = {2020}, author = {Nelson, WJ}, title = {The Glue that Binds Us: The Hunt for the Molecular Basis for Multicellularity.}, journal = {Cell}, volume = {181}, number = {3}, pages = {495-497}, doi = {10.1016/j.cell.2020.03.017}, pmid = {32234519}, issn = {1097-4172}, mesh = {Animals ; Awards and Prizes ; Biophysical Phenomena ; Cadherins/*metabolism/*physiology ; Canada ; Cell Adhesion/physiology ; Cell Communication/*physiology ; History, 20th Century ; History, 21st Century ; Homeostasis/physiology ; Humans ; Male ; }, abstract = {This year's Canada Gairdner International Prize is shared by Rolf Kemler and Masatoshi Takeichi for the discovery of the cadherin family of Ca[2+]-dependent cell-cell adhesion proteins, which play essential roles in animal evolution, tissue development, and homeostasis, and are disrupted in human cancers.}, } @article {pmid32226593, year = {2020}, author = {Xu, H and Zhang, S and Yi, X and Plewczynski, D and Li, MJ}, title = {Exploring 3D chromatin contacts in gene regulation: The evolution of approaches for the identification of functional enhancer-promoter interaction.}, journal = {Computational and structural biotechnology journal}, volume = {18}, number = {}, pages = {558-570}, pmid = {32226593}, issn = {2001-0370}, abstract = {Mechanisms underlying gene regulation are key to understand how multicellular organisms with various cell types develop from the same genetic blueprint. Dynamic interactions between enhancers and genes are revealed to play central roles in controlling gene transcription, but the determinants to link functional enhancer-promoter pairs remain elusive. A major challenge is the lack of reliable approach to detect and verify functional enhancer-promoter interactions (EPIs). In this review, we summarized the current methods for detecting EPIs and described how developing techniques facilitate the identification of EPI through assessing the merits and drawbacks of these methods. We also reviewed recent state-of-art EPI prediction methods in terms of their rationale, data usage and characterization. Furthermore, we briefly discussed the evolved strategies for validating functional EPIs.}, } @article {pmid32224105, year = {2020}, author = {Mikhailovsky, G and Gordon, R}, title = {Shuffling type of biological evolution based on horizontal gene transfer and the biosphere gene pool hypothesis.}, journal = {Bio Systems}, volume = {193-194}, number = {}, pages = {104131}, doi = {10.1016/j.biosystems.2020.104131}, pmid = {32224105}, issn = {1872-8324}, mesh = {*Biological Evolution ; DNA Shuffling/*methods ; Eukaryota/genetics ; *Evolution, Molecular ; *Gene Pool ; Gene Transfer, Horizontal/*genetics ; Prokaryotic Cells/physiology ; }, abstract = {Widespread horizontal gene transfer (HGT) may appear a significant factor that accelerates biological evolution. Here we look at HGT primarily from the point of view of prokaryote clones, which we take as the descendants of a single cell, all of whom have exactly the same nucleotide sequence. Any novelty that emerges as a random mutation, creating a new clone, could either disappear before its first HGT, or survive for a period and be transferred to another clone. Due to the chain character of HGT, each gene with an adaptive mutation is thus spread among numerous existing clones, creating further new clones in the process. This makes propagation far faster than elimination, and such genes become practically immortal and form a kind of "biosphere gene pool" (BGP). Not all of these genes exist in every clone, and moreover not all of them are expressed. A significant fraction of the BGP includes of genes repressed by regulatory genes. However, these genes express often enough to be subject to natural selection. In a changing environment, both repressed and expressed genes, after transferring to another clone, may prove useful in an alternative environment, and this will give rise to new clones. This mechanism for testing repressed genes for adaptability can be thought as a "shuffle of a deck of genes" by analogy with shuffling a deck of cards. In the Archean and Proterozoic eons, both BGP and the operational part of each genome were rather poor, and the probability of incorporation of randomly expressed genes into the operational part of each genome was very small. Accordingly, biological evolution during these eons was slow due to rare adaptive mutations. This explains why the realm of prokaryotes as the sole organisms on Earth lasted so long. However, over about 3.5 billion years before the Phanerozoic eon, the BGP gradually accumulated a huge number of genes. Each of them was useful in a certain environment of past eras. We suggest that multicellular eukaryotes that appeared at the end of the Proterozoic eon could shuffle these genes accumulated in BGP via HGT from prokaryotes that live in these multicellular organisms. Perhaps this was the cause of the "Cambrian explosion" and the high (and increasing) rate of evolution in the Phanerozoic eon compared with the Archean and Proterozoic.}, } @article {pmid32220299, year = {2020}, author = {Aich, M and Chakraborty, D}, title = {Role of lncRNAs in stem cell maintenance and differentiation.}, journal = {Current topics in developmental biology}, volume = {138}, number = {}, pages = {73-112}, doi = {10.1016/bs.ctdb.2019.11.003}, pmid = {32220299}, issn = {1557-8933}, mesh = {Animals ; Cell Differentiation ; Cell Proliferation ; Embryonic Stem Cells/cytology/*physiology ; *Gene Expression Regulation, Developmental ; Humans ; Pluripotent Stem Cells/cytology/*physiology ; Promoter Regions, Genetic ; RNA, Long Noncoding/genetics/*metabolism ; Regulatory Sequences, Nucleic Acid ; }, abstract = {Embryonic Stem cells are widely studied to elucidate the disease and developmental processes because of their capability to differentiate into cells of any lineage, Pervasive transcription is a distinct feature of all multicellular organisms and genomic elements such as enhancers and bidirectional or unidirectional promoters regulate these processes. Thousands of loci in each species produce a class of transcripts called noncoding RNAs (ncRNAs), that are well known for their influential regulatory roles in multiple biological processes including stem cell pluripotency and differentiation. The number of lncRNA species increases in more complex organisms highlighting the importance of RNA-based control in the evolution of multicellular organisms. Over the past decade, numerous studies have shed light on lncRNA biogenesis and functional significance in the cell and the organism. In this review, we focus primarily on lncRNAs affecting the stem cell state and developmental pathways.}, } @article {pmid32206719, year = {2020}, author = {Guo, Z and Richardson, JJ and Kong, B and Liang, K}, title = {Nanobiohybrids: Materials approaches for bioaugmentation.}, journal = {Science advances}, volume = {6}, number = {12}, pages = {eaaz0330}, pmid = {32206719}, issn = {2375-2548}, mesh = {Biocatalysis ; Biocompatible Materials/chemical synthesis/*chemistry ; *Bioengineering/methods ; Cell Survival ; Chemistry Techniques, Synthetic ; Nanostructures/*chemistry ; Nanotechnology ; Tissue Scaffolds ; }, abstract = {Nanobiohybrids, synthesized by integrating functional nanomaterials with living systems, have emerged as an exciting branch of research at the interface of materials engineering and biological science. Nanobiohybrids use synthetic nanomaterials to impart organisms with emergent properties outside their scope of evolution. Consequently, they endow new or augmented properties that are either innate or exogenous, such as enhanced tolerance against stress, programmed metabolism and proliferation, artificial photosynthesis, or conductivity. Advances in new materials design and processing technologies made it possible to tailor the physicochemical properties of the nanomaterials coupled with the biological systems. To date, many different types of nanomaterials have been integrated with various biological systems from simple biomolecules to complex multicellular organisms. Here, we provide a critical overview of recent developments of nanobiohybrids that enable new or augmented biological functions that show promise in high-tech applications across many disciplines, including energy harvesting, biocatalysis, biosensing, medicine, and robotics.}, } @article {pmid32198827, year = {2021}, author = {Koehl, MAR}, title = {Selective factors in the evolution of multicellularity in choanoflagellates.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {336}, number = {3}, pages = {315-326}, doi = {10.1002/jez.b.22941}, pmid = {32198827}, issn = {1552-5015}, mesh = {Animals ; Bacteria ; Behavior, Animal ; *Biological Evolution ; Choanoflagellata/*growth & development/*physiology ; Predatory Behavior ; }, abstract = {Choanoflagellates, unicellular eukaryotes that can form multicellular colonies by cell division and that share a common ancestor with animals, are used as a model system to study functional consequences of being unicellular versus colonial. This review examines performance differences between unicellular and multicellular choanoflagellates in swimming, feeding, and avoiding predation, to provide insights about possible selective advantages of being multicellular for the protozoan ancestors of animals. Each choanoflagellate cell propels water by beating a single flagellum and captures bacterial prey on a collar of microvilli around the flagellum. Formation of multicellular colonies does not improve the swimming performance, but the flux of prey-bearing water to the collars of some of the cells in colonies of certain configurations can be greater than for single cells. Colony geometry appears to affect whether cells in colonies catch more prey per cell per time than do unicellular choanoflagellates. Although multicellular choanoflagellates show chemokinetic behavior in response to oxygen, only the unicellular dispersal stage (fast swimmers without collars) use pH signals to aggregate in locations where bacterial prey might be abundant. Colonies produce larger hydrodynamic signals than do single cells, and raptorial protozoan predators capture colonies while ignoring single cells. In contrast, ciliate predators entrain both single cells and colonies in their feeding currents, but reject larger colonies, whereas passive heliozoan predators show no preference. Thus, the ability of choanoflagellate cells to differentiate into different morphotypes, including multicellular forms, in response to variable aquatic environments might have provided a selective advantage to the ancestors of animals.}, } @article {pmid32191693, year = {2020}, author = {Rossine, FW and Martinez-Garcia, R and Sgro, AE and Gregor, T and Tarnita, CE}, title = {Eco-evolutionary significance of "loners".}, journal = {PLoS biology}, volume = {18}, number = {3}, pages = {e3000642}, pmid = {32191693}, issn = {1545-7885}, support = {F32 GM103062/GM/NIGMS NIH HHS/United States ; K25 GM098875/GM/NIGMS NIH HHS/United States ; P50 GM071508/GM/NIGMS NIH HHS/United States ; R01 GM098407/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Dictyostelium/growth & development/*physiology ; Models, Biological ; Quorum Sensing ; Spatio-Temporal Analysis ; Stochastic Processes ; }, abstract = {Loners-individuals out of sync with a coordinated majority-occur frequently in nature. Are loners incidental byproducts of large-scale coordination attempts, or are they part of a mosaic of life-history strategies? Here, we provide empirical evidence of naturally occurring heritable variation in loner behavior in the model social amoeba Dictyostelium discoideum. We propose that Dictyostelium loners-cells that do not join the multicellular life stage-arise from a dynamic population-partitioning process, the result of each cell making a stochastic, signal-based decision. We find evidence that this imperfectly synchronized multicellular development is affected by both abiotic (environmental porosity) and biotic (signaling) factors. Finally, we predict theoretically that when a pair of strains differing in their partitioning behavior coaggregate, cross-signaling impacts slime-mold diversity across spatiotemporal scales. Our findings suggest that loners could be critical to understanding collective and social behaviors, multicellular development, and ecological dynamics in D. discoideum. More broadly, across taxa, imperfect coordination of collective behaviors might be adaptive by enabling diversification of life-history strategies.}, } @article {pmid32191325, year = {2020}, author = {Merényi, Z and Prasanna, AN and Wang, Z and Kovács, K and Hegedüs, B and Bálint, B and Papp, B and Townsend, JP and Nagy, LG}, title = {Unmatched Level of Molecular Convergence among Deeply Divergent Complex Multicellular Fungi.}, journal = {Molecular biology and evolution}, volume = {37}, number = {8}, pages = {2228-2240}, pmid = {32191325}, issn = {1537-1719}, support = {758161/ERC_/European Research Council/International ; }, mesh = {Ascomycota/*genetics ; Basidiomycota/*genetics ; *Biological Evolution ; Fruiting Bodies, Fungal/*genetics ; Gene Expression Regulation, Developmental ; Multigene Family ; }, abstract = {Convergent evolution is pervasive in nature, but it is poorly understood how various constraints and natural selection limit the diversity of evolvable phenotypes. Here, we analyze the transcriptome across fruiting body development to understand the independent evolution of complex multicellularity in the two largest clades of fungi-the Agarico- and Pezizomycotina. Despite >650 My of divergence between these clades, we find that very similar sets of genes have convergently been co-opted for complex multicellularity, followed by expansions of their gene families by duplications. Over 82% of shared multicellularity-related gene families were expanding in both clades, indicating a high prevalence of convergence also at the gene family level. This convergence is coupled with a rich inferred repertoire of multicellularity-related genes in the most recent common ancestor of the Agarico- and Pezizomycotina, consistent with the hypothesis that the coding capacity of ancestral fungal genomes might have promoted the repeated evolution of complex multicellularity. We interpret this repertoire as an indication of evolutionary predisposition of fungal ancestors for evolving complex multicellular fruiting bodies. Our work suggests that evolutionary convergence may happen not only when organisms are closely related or are under similar selection pressures, but also when ancestral genomic repertoires render certain evolutionary trajectories more likely than others, even across large phylogenetic distances.}, } @article {pmid32188162, year = {2020}, author = {Zhang, WJ and Wu, LF}, title = {Flagella and Swimming Behavior of Marine Magnetotactic Bacteria.}, journal = {Biomolecules}, volume = {10}, number = {3}, pages = {}, pmid = {32188162}, issn = {2218-273X}, support = {A-M-AAP-EI-17-07-170301-07.50-WU-ENV//Fondation Aix-Marseille Universite/International ; LIA-MagMC//Centre National de la Recherche Scientifique/International ; 91751202//National Natural Science Foundation of China/International ; 91751108//National Natural Science Foundation of China/International ; }, mesh = {*Aquatic Organisms/metabolism/ultrastructure ; *Bacteria/metabolism/ultrastructure ; *Flagella/metabolism/ultrastructure ; *Magnetic Fields ; }, abstract = {Marine environments are generally characterized by low bulk concentrations of nutrients that are susceptible to steady or intermittent motion driven by currents and local turbulence. Marine bacteria have therefore developed strategies, such as very fast-swimming and the exploitation of multiple directional sensing-response systems in order to efficiently migrate towards favorable places in nutrient gradients. The magnetotactic bacteria (MTB) even utilize Earth's magnetic field to facilitate downward swimming into the oxic-anoxic interface, which is the most favorable place for their persistence and proliferation, in chemically stratified sediments or water columns. To ensure the desired flagella-propelled motility, marine MTBs have evolved an exquisite flagellar apparatus, and an extremely high number (tens of thousands) of flagella can be found on a single entity, displaying a complex polar, axial, bounce, and photosensitive magnetotactic behavior. In this review, we describe gene clusters, the flagellar apparatus architecture, and the swimming behavior of marine unicellular and multicellular magnetotactic bacteria. The physiological significance and mechanisms that govern these motions are discussed.}, } @article {pmid32188079, year = {2020}, author = {Gura, C and Rogers, SO}, title = {Metatranscriptomic and Metagenomic Analysis of Biological Diversity in Subglacial Lake Vostok (Antarctica).}, journal = {Biology}, volume = {9}, number = {3}, pages = {}, pmid = {32188079}, issn = {2079-7737}, support = {ANT-0536870//National Science Foundation/ ; }, abstract = {A combined metatranscriptomic and metagenomic study of Vostok (Antarctica) ice core sections from glacial, basal, and lake water accretion ice yielded sequences that indicated a wide variety of species and possible conditions at the base of the glacier and in subglacial Lake Vostok. Few organisms were in common among the basal ice and accretion ice samples, suggesting little transmission of viable organisms from the basal ice meltwater into the lake water. Additionally, samples of accretion ice, each of which originated from water in several locations of the shallow embayment, exhibit only small amounts of mixing of species. The western-most portion of the embayment had very low numbers of organisms, likely due to biologically challenging conditions. Increasing numbers of organisms were found progressing from west to east, up to approximately 7 km into the embayment. At that point, the numbers of unique sequences and sequence reads from thermophilic, thermotolerant, psychrophilic, and psychrotolerant organisms increased dramatically, as did sequences from alkaliphilic, alkalitolerant, acidophilic, and acidotolerant sequences. The number of unique and total sequences were positively associated with increases in concentrations of Na[+], Ca[2+], Mg[2+], SO4[2-], Cl[-], total amino acids, and non-purgeable organic carbon. The numbers of unique sequences from organisms reported from soil, sediment, ice, aquatic, marine, animal, and plant (probably pollen) sources also peaked in this region, suggesting that this was the most biologically active region. The confluence of the high numbers of organisms, physiologies, and metabolic capabilities suggests the presence of energy and nutrient sources in the eastern half of the embayment. Data from the main basin suggested a cold oligotrophic environment containing fewer organisms. In addition to bacteria, both the basal ice and accretion ice contained sequences from a diverse assemblage of eukaryotes, as well as from bacteria that are known to be associated with multicellular eukaryotes.}, } @article {pmid32188032, year = {2020}, author = {Goyeneche, A and Lisio, MA and Fu, L and Srinivasan, R and Valdez Capuccino, J and Gao, ZH and Telleria, C}, title = {The Capacity of High-Grade Serous Ovarian Cancer Cells to Form Multicellular Structures Spontaneously along Disease Progression Correlates with Their Orthotopic Tumorigenicity in Immunosuppressed Mice.}, journal = {Cancers}, volume = {12}, number = {3}, pages = {}, pmid = {32188032}, issn = {2072-6694}, support = {35635//Canada Foundation for Innovation/ ; 164222/CA/NCI NIH HHS/United States ; }, abstract = {Many studies have examined the biology, genetics, and chemotherapeutic response of ovarian cancer's solid component; its liquid facet, however, remains critically underinvestigated. Floating within peritoneal effusions known as ascites, ovarian cancer cells form multicellular structures, creating a cancer niche in suspension. This study explores the pathobiology of spontaneously formed, multicellular, ovarian cancer structures derived from serous ovarian cancer cells isolated along disease evolution. It also tests their capacity to cause peritoneal disease in immunosuppressed mice. Results stem from an analysis of cell lines representing the most frequently diagnosed ovarian cancer histotype (high-grade serous ovarian cancer), derived from ascites of the same patient at distinct stages of disease progression. When cultured under adherent conditions, in addition to forming cellular monolayers, the cultures developed areas in which the cells grew upwards, forming densely packed multilayers that ultimately detached from the bottom of the plates and lived as free-floating, multicellular structures. The capacity to form foci and to develop multicellular structures was proportional to disease progression at the time of ascites extraction. Self-assembled in culture, these structures varied in size, were either compact or hollow, irregular, or spheroidal, and exhibited replicative capacity and an epithelial nature. Furthermore, they fully recreated ovarian cancer disease in immunosuppressed mice: accumulation of malignant ascites and pleural effusions; formation of discrete, solid, macroscopic, peritoneal tumors; and microscopic growths in abdominal organs. They also reproduced the histopathological features characteristic of high-grade serous ovarian cancer when diagnosed in patients. The following results encourage the development of therapeutic interventions to interrupt the formation and/or survival of multicellular structures that constitute a floating niche in the peritoneal fluid, which in turn halts disease progression and prevents recurrence.}, } @article {pmid32182341, year = {2020}, author = {Mageeney, CM and Lau, BY and Wagner, JM and Hudson, CM and Schoeniger, JS and Krishnakumar, R and Williams, KP}, title = {New candidates for regulated gene integrity revealed through precise mapping of integrative genetic elements.}, journal = {Nucleic acids research}, volume = {48}, number = {8}, pages = {4052-4065}, pmid = {32182341}, issn = {1362-4962}, mesh = {Algorithms ; Attachment Sites, Microbiological ; *DNA Transposable Elements ; *Genes, Bacterial ; Genome, Archaeal ; Genome, Bacterial ; Genomics/methods ; Integrases/classification/genetics ; Phylogeny ; Recombination, Genetic ; *Software ; }, abstract = {Integrative genetic elements (IGEs) are mobile multigene DNA units that integrate into and excise from host bacterial genomes. Each IGE usually targets a specific site within a conserved host gene, integrating in a manner that preserves target gene function. However, a small number of bacterial genes are known to be inactivated upon IGE integration and reactivated upon excision, regulating phenotypes of virulence, mutation rate, and terminal differentiation in multicellular bacteria. The list of regulated gene integrity (RGI) cases has been slow-growing because IGEs have been challenging to precisely and comprehensively locate in genomes. We present software (TIGER) that maps IGEs with unprecedented precision and without attB site bias. TIGER uses a comparative genomic, ping-pong BLAST approach, based on the principle that the IGE integration module (i.e. its int-attP region) is cohesive. The resultant IGEs from 2168 genomes, along with integrase phylogenetic analysis and gene inactivation tests, revealed 19 new cases of genes whose integrity is regulated by IGEs (including dut, eccCa1, gntT, hrpB, merA, ompN, prkA, tqsA, traG, yifB, yfaT and ynfE), as well as recovering previously known cases (in sigK, spsM, comK, mlrA and hlb genes). It also recovered known clades of site-promiscuous integrases and identified possible new ones.}, } @article {pmid32168596, year = {2020}, author = {de Maleprade, H and Moisy, F and Ishikawa, T and Goldstein, RE}, title = {Motility and phototaxis of Gonium, the simplest differentiated colonial alga.}, journal = {Physical review. E}, volume = {101}, number = {2-1}, pages = {022416}, doi = {10.1103/PhysRevE.101.022416}, pmid = {32168596}, issn = {2470-0053}, support = {207510/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Comamonadaceae/*physiology/*radiation effects ; Hydrodynamics ; Models, Biological ; *Phototaxis ; Rotation ; }, abstract = {Green algae of the Volvocine lineage, spanning from unicellular Chlamydomonas to vastly larger Volvox, are models for the study of the evolution of multicellularity, flagellar dynamics, and developmental processes. Phototactic steering in these organisms occurs without a central nervous system, driven solely by the response of individual cells. All such algae spin about a body-fixed axis as they swim; directional photosensors on each cell thus receive periodic signals when that axis is not aligned with the light. The flagella of Chlamydomonas and Volvox both exhibit an adaptive response to such signals in a manner that allows for accurate phototaxis, but in the former the two flagella have distinct responses, while the thousands of flagella on the surface of spherical Volvox colonies have essentially identical behavior. The planar 16-cell species Gonium pectorale thus presents a conundrum, for its central 4 cells have a Chlamydomonas-like beat that provide propulsion normal to the plane, while its 12 peripheral cells generate rotation around the normal through a Volvox-like beat. Here we combine experiment, theory, and computations to reveal how Gonium, perhaps the simplest differentiated colonial organism, achieves phototaxis. High-resolution cell tracking, particle image velocimetry of flagellar driven flows, and high-speed imaging of flagella on micropipette-held colonies show how, in the context of a recently introduced model for Chlamydomonas phototaxis, an adaptive response of the peripheral cells alone leads to photoreorientation of the entire colony. The analysis also highlights the importance of local variations in flagellar beat dynamics within a given colony, which can lead to enhanced reorientation dynamics.}, } @article {pmid32168362, year = {2020}, author = {Morgan, MD and Patin, E and Jagla, B and Hasan, M and Quintana-Murci, L and Marioni, JC}, title = {Quantitative genetic analysis deciphers the impact of cis and trans regulation on cell-to-cell variability in protein expression levels.}, journal = {PLoS genetics}, volume = {16}, number = {3}, pages = {e1008686}, pmid = {32168362}, issn = {1553-7404}, support = {MR/M008975/1/MRC_/Medical Research Council/United Kingdom ; 105045/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; 17197/CRUK_/Cancer Research UK/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Alleles ; Databases, Genetic ; Female ; Gene Expression/*genetics ; Gene Expression Profiling/methods ; Gene Expression Regulation/*genetics ; Genetic Testing/methods ; Genome-Wide Association Study/methods ; Humans ; Immune System/metabolism ; Immunity/genetics ; Male ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci/genetics ; Selection, Genetic/genetics ; }, abstract = {Identifying the factors that shape protein expression variability in complex multi-cellular organisms has primarily focused on promoter architecture and regulation of single-cell expression in cis. However, this targeted approach has to date been unable to identify major regulators of cell-to-cell gene expression variability in humans. To address this, we have combined single-cell protein expression measurements in the human immune system using flow cytometry with a quantitative genetics analysis. For the majority of proteins whose variability in expression has a heritable component, we find that genetic variants act in trans, with notably fewer variants acting in cis. Furthermore, we highlight using Mendelian Randomization that these variability-Quantitative Trait Loci might be driven by the cis regulation of upstream genes. This indicates that natural selection may balance the impact of gene regulation in cis with downstream impacts on expression variability in trans.}, } @article {pmid32163611, year = {2020}, author = {Nedelcu, AM and Michod, RE}, title = {Stress Responses Co-Opted for Specialized Cell Types During the Early Evolution of Multicellularity: The Role of Stress in the Evolution of Cell Types Can Be Traced Back to the Early Evolution of Multicellularity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {42}, number = {5}, pages = {e2000029}, doi = {10.1002/bies.202000029}, pmid = {32163611}, issn = {1521-1878}, support = {//Natural Sciences and Engineering Research Council (NSERC) of Canada and Harrison McCain Foundation/International ; NNX13AH41G/NASA/NASA/United States ; MCB-1412395//National Science Foundation/International ; //Natural Sciences and Engineering Research Council of Canada/International ; NNX13AH41G/NASA/NASA/United States ; }, mesh = {*Biological Evolution ; Humans ; Phylogeny ; }, } @article {pmid32163413, year = {2020}, author = {Rodríguez-Rojas, A and Kim, JJ and Johnston, PR and Makarova, O and Eravci, M and Weise, C and Hengge, R and Rolff, J}, title = {Non-lethal exposure to H2O2 boosts bacterial survival and evolvability against oxidative stress.}, journal = {PLoS genetics}, volume = {16}, number = {3}, pages = {e1008649}, pmid = {32163413}, issn = {1553-7404}, mesh = {Drug Resistance ; Escherichia coli/*drug effects/metabolism ; Escherichia coli Proteins/metabolism ; Evolution, Molecular ; Hydrogen Peroxide/*pharmacology ; Oxidative Stress/*drug effects/physiology ; Reactive Oxygen Species/metabolism ; }, abstract = {Unicellular organisms have the prevalent challenge to survive under oxidative stress of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2). ROS are present as by-products of photosynthesis and aerobic respiration. These reactive species are even employed by multicellular organisms as potent weapons against microbes. Although bacterial defences against lethal and sub-lethal oxidative stress have been studied in model bacteria, the role of fluctuating H2O2 concentrations remains unexplored. It is known that sub-lethal exposure of Escherichia coli to H2O2 results in enhanced survival upon subsequent exposure. Here we investigate the priming response to H2O2 at physiological concentrations. The basis and the duration of the response (memory) were also determined by time-lapse quantitative proteomics. We found that a low level of H2O2 induced several scavenging enzymes showing a long half-life, subsequently protecting cells from future exposure. We then asked if the phenotypic resistance against H2O2 alters the evolution of resistance against oxygen stress. Experimental evolution of H2O2 resistance revealed faster evolution and higher levels of resistance in primed cells. Several mutations were found to be associated with resistance in evolved populations affecting different loci but, counterintuitively, none of them was directly associated with scavenging systems. Our results have important implications for host colonisation and infections where microbes often encounter reactive oxygen species in gradients.}, } @article {pmid32146616, year = {2020}, author = {Fuchs, M and Lohmann, JU}, title = {Aiming for the top: non-cell autonomous control of shoot stem cells in Arabidopsis.}, journal = {Journal of plant research}, volume = {133}, number = {3}, pages = {297-309}, pmid = {32146616}, issn = {1618-0860}, support = {SFB873//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Arabidopsis/*growth & development ; Arabidopsis Proteins ; Gene Expression Regulation, Plant ; Homeodomain Proteins ; Meristem/*cytology ; Plant Shoots/*cytology ; Stem Cells/*cytology ; }, abstract = {In multicellular organisms, not all cells are created equal. Instead, organismal complexity is achieved by specialisation and division of labour between distinct cell types. Therefore, the organism depends on the presence, correct proportion and function of all cell types. It follows that early development is geared towards setting up the basic body plan and to specify cell lineages. Since plants employ a post-embryonic mode of development, the continuous growth and addition of new organs require a source of new cells, as well as a strict regulation of cellular composition throughout the entire life-cycle. To meet these demands, evolution has brought about complex regulatory systems to maintain and control continuously active stem cell systems. Here, we review recent work on the mechanisms of non cell-autonomous control of shoot stem cells in the model plant Arabidopsis thaliana with a strong focus on the cell-to-cell mobility and function of the WUSCHEL homeodomain transcription factor.}, } @article {pmid32143753, year = {2020}, author = {Klesen, S and Hill, K and Timmermans, MCP}, title = {Small RNAs as plant morphogens.}, journal = {Current topics in developmental biology}, volume = {137}, number = {}, pages = {455-480}, doi = {10.1016/bs.ctdb.2019.11.001}, pmid = {32143753}, issn = {1557-8933}, mesh = {Cell Communication ; *Gene Expression Regulation, Developmental ; MicroRNAs/genetics ; *Plant Development ; *Plant Physiological Phenomena ; Plant Proteins/genetics/*metabolism ; Plants/*genetics ; RNA/*genetics ; RNA, Small Interfering/genetics ; Signal Transduction ; }, abstract = {The coordination of cell fate decisions within complex multicellular structures rests on intercellular communication. To generate ordered patterns, cells need to know their relative positions within the growing structure. This is commonly achieved via the production and perception of mobile signaling molecules. In animal systems, such positional signals often act as morphogens and subdivide a field of cells into domains of discrete cell identities using a threshold-based readout of their mobility gradient. Reflecting the independent origin of multicellularity, plants evolved distinct signaling mechanisms to drive cell fate decisions. Many of the basic principles underlying developmental patterning are, however, shared between animals and plants, including the use of signaling gradients to provide positional information. In plant development, small RNAs can act as mobile instructive signals, and similar to classical morphogens in animals, employ a threshold-based readout of their mobility gradient to generate precisely defined cell fate boundaries. Given the distinctive nature of peptide morphogens and small RNAs, how might mechanisms underlying the function of traditionally morphogens be adapted to create morphogen-like behavior using small RNAs? In this review, we highlight the contributions of mobile small RNAs to pattern formation in plants and summarize recent studies that have advanced our understanding regarding the formation, stability, and interpretation of small RNA gradients.}, } @article {pmid32139673, year = {2020}, author = {Han, H and Yan, A and Li, L and Zhu, Y and Feng, B and Liu, X and Zhou, Y}, title = {A signal cascade originated from epidermis defines apical-basal patterning of Arabidopsis shoot apical meristems.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {1214}, pmid = {32139673}, issn = {2041-1723}, mesh = {Arabidopsis/*embryology/genetics/*metabolism ; Arabidopsis Proteins/metabolism ; Base Sequence ; *Body Patterning ; Gene Expression Regulation, Plant ; Green Fluorescent Proteins/metabolism ; Homeodomain Proteins/metabolism ; Meristem/*embryology/*metabolism ; MicroRNAs/genetics/metabolism ; Plant Epidermis/*metabolism ; Promoter Regions, Genetic/genetics ; Protein Binding ; *Signal Transduction ; Stem Cell Niche ; Up-Regulation/genetics ; }, abstract = {In multicellular organisms, a long-standing question is how spatial patterns of distinct cell types are initiated and maintained during continuous cell division and proliferation. Along the vertical axis of plant shoot apical meristems (SAMs), stem cells are located at the top while cells specifying the stem cells are located more basally, forming a robust apical-basal pattern. We previously found that in Arabidopsis SAMs, the HAIRY MERISTEM (HAM) family transcription factors form a concentration gradient from the epidermis to the interior cell layers, and this gradient is essential for the stem cell specification and the apical-basal patterning of the SAMs. Here, we uncover that epidermis specific transcription factors, ARABIDOPSIS THALIANA MERISTEM LAYER 1 (ATML1) and its close homolog, define the concentration gradient of HAM in the SAM through activating a group of microRNAs. This study provides a molecular framework linking the epidermis-derived signal to the stem cell homeostasis in plants.}, } @article {pmid32133683, year = {2020}, author = {Horton, MB and Hawkins, ED and Heinzel, S and Hodgkin, PD}, title = {Speculations on the evolution of humoral adaptive immunity.}, journal = {Immunology and cell biology}, volume = {98}, number = {6}, pages = {439-448}, pmid = {32133683}, issn = {1440-1711}, mesh = {*Adaptive Immunity ; *Biological Evolution ; Cell Differentiation ; Humans ; *Immunity, Humoral ; }, abstract = {The protection of a multicellular organism from infection, at both cell and humoral levels, has been a tremendous driver of gene selection and cellular response strategies. Here we focus on a critical event in the development of humoral immunity: The transition from principally innate responses to a system of adaptive cell selection, with all the attendant mechanical problems that must be solved in order for it to work effectively. Here we review recent advances, but our major goal is to highlight that the development of adaptive immunity resulted from the adoption, reuse and repurposing of an ancient, autonomous cellular program that combines and exploits three titratable cellular fate timers. We illustrate how this common cell machinery recurs and appears throughout biology, and has been essential for the evolution of complex organisms, at many levels of scale.}, } @article {pmid32130880, year = {2020}, author = {González, A and Hall, MN and Lin, SC and Hardie, DG}, title = {AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control.}, journal = {Cell metabolism}, volume = {31}, number = {3}, pages = {472-492}, doi = {10.1016/j.cmet.2020.01.015}, pmid = {32130880}, issn = {1932-7420}, support = {204766/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204766/WT_/Wellcome Trust/United Kingdom ; }, mesh = {AMP-Activated Protein Kinases/chemistry/genetics/*metabolism ; Animals ; Cell Proliferation ; Cells/*metabolism ; DNA Damage ; Humans ; Nutrients/*metabolism ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {The AMPK (AMP-activated protein kinase) and TOR (target-of-rapamycin) pathways are interlinked, opposing signaling pathways involved in sensing availability of nutrients and energy and regulation of cell growth. AMPK (Yin, or the "dark side") is switched on by lack of energy or nutrients and inhibits cell growth, while TOR (Yang, or the "bright side") is switched on by nutrient availability and promotes cell growth. Genes encoding the AMPK and TOR complexes are found in almost all eukaryotes, suggesting that these pathways arose very early during eukaryotic evolution. During the development of multicellularity, an additional tier of cell-extrinsic growth control arose that is mediated by growth factors, but these often act by modulating nutrient uptake so that AMPK and TOR remain the underlying regulators of cellular growth control. In this review, we discuss the evolution, structure, and regulation of the AMPK and TOR pathways and the complex mechanisms by which they interact.}, } @article {pmid32130562, year = {2020}, author = {Lashkarinia, SS and Çoban, G and Ermek, E and Çelik, M and Pekkan, K}, title = {Spatiotemporal remodeling of embryonic aortic arch: stress distribution, microstructure, and vascular growth in silico.}, journal = {Biomechanics and modeling in mechanobiology}, volume = {19}, number = {5}, pages = {1897-1915}, doi = {10.1007/s10237-020-01315-6}, pmid = {32130562}, issn = {1617-7940}, support = {307460/ERC_/European Research Council/International ; }, mesh = {Animals ; Aorta, Thoracic/*anatomy & histology/*embryology ; Chickens ; Collagen Type I/metabolism ; *Computer Simulation ; Finite Element Analysis ; Imaging, Three-Dimensional ; *Models, Anatomic ; Pressure ; Reproducibility of Results ; Stress, Mechanical ; }, abstract = {The microstructure for mature vessels has been investigated in detail, while there is limited information about the embryonic stages, in spite of their importance in the prognosis of congenital heart defects. It is hypothesized that the embryonic vasculature represents a disorganized but dynamic soft tissue, which rapidly evolves toward a specialized multi-cellular vascular structure under mechanical loading. Here the microstructural evolution process of the embryonic pharyngeal aortic arch structure was simulated using an in ovo validated long-term growth and remodeling computational model, implemented as an in-house FEBio plug-in. Optical coherence tomography-guided servo-null pressure measurements are assigned as boundary conditions through the critical embryonic stages. The accumulation of key microstructural constituents was recorded through zoom confocal microscopy for all six embryonic arch arteries simultaneously. The total amount and the radial variation slope of the collagen along the arch wall thickness in different arch types and for different embryonic times, with different dimension scales, were normalized and compared statistically. The arch growth model shows that the stress levels around the lumen boundary increase from [Formula: see text] (Stage 18) to a level higher than [Formula: see text] (Stage 24), depending on matrix constituent production rates, while the homeostatic strain level is kept constant. The statistical tests show that although the total collagen levels differentiate among bilateral positions of the same arch, the shape coefficient of the matrix microstructural gradient changes with embryonic time, proving radial localization, in accordance with numerical model results. In vivo cell number (DAPI) and vascular endothelial growth factor distributions followed similar trends.}, } @article {pmid32130216, year = {2020}, author = {Ronquist, F and Forshage, M and Häggqvist, S and Karlsson, D and Hovmöller, R and Bergsten, J and Holston, K and Britton, T and Abenius, J and Andersson, B and Buhl, PN and Coulianos, CC and Fjellberg, A and Gertsson, CA and Hellqvist, S and Jaschhof, M and Kjærandsen, J and Klopfstein, S and Kobro, S and Liston, A and Meier, R and Pollet, M and Riedel, M and Roháček, J and Schuppenhauer, M and Stigenberg, J and Struwe, I and Taeger, A and Ulefors, SO and Varga, O and Withers, P and Gärdenfors, U}, title = {Completing Linnaeus's inventory of the Swedish insect fauna: Only 5,000 species left?.}, journal = {PloS one}, volume = {15}, number = {3}, pages = {e0228561}, pmid = {32130216}, issn = {1932-6203}, mesh = {Animals ; *Biodiversity ; *Censuses ; Diptera/classification ; Ecosystem ; Europe ; *Extinction, Biological ; Insecta/*classification ; Phylogeny ; Records ; Sweden ; }, abstract = {Despite more than 250 years of taxonomic research, we still have only a vague idea about the true size and composition of the faunas and floras of the planet. Many biodiversity inventories provide limited insight because they focus on a small taxonomic subsample or a tiny geographic area. Here, we report on the size and composition of the Swedish insect fauna, thought to represent roughly half of the diversity of multicellular life in one of the largest European countries. Our results are based on more than a decade of data from the Swedish Taxonomy Initiative and its massive inventory of the country's insect fauna, the Swedish Malaise Trap Project The fauna is considered one of the best known in the world, but the initiative has nevertheless revealed a surprising amount of hidden diversity: more than 3,000 new species (301 new to science) have been documented so far. Here, we use three independent methods to analyze the true size and composition of the fauna at the family or subfamily level: (1) assessments by experts who have been working on the most poorly known groups in the fauna; (2) estimates based on the proportion of new species discovered in the Malaise trap inventory; and (3) extrapolations based on species abundance and incidence data from the inventory. For the last method, we develop a new estimator, the combined non-parametric estimator, which we show is less sensitive to poor coverage of the species pool than other popular estimators. The three methods converge on similar estimates of the size and composition of the fauna, suggesting that it comprises around 33,000 species. Of those, 8,600 (26%) were unknown at the start of the inventory and 5,000 (15%) still await discovery. We analyze the taxonomic and ecological composition of the estimated fauna, and show that most of the new species belong to Hymenoptera and Diptera groups that are decomposers or parasitoids. Thus, current knowledge of the Swedish insect fauna is strongly biased taxonomically and ecologically, and we show that similar but even stronger biases have distorted our understanding of the fauna in the past. We analyze latitudinal gradients in the size and composition of known European insect faunas and show that several of the patterns contradict the Swedish data, presumably due to similar knowledge biases. Addressing these biases is critical in understanding insect biomes and the ecosystem services they provide. Our results emphasize the need to broaden the taxonomic scope of current insect monitoring efforts, a task that is all the more urgent as recent studies indicate a possible worldwide decline in insect faunas.}, } @article {pmid32129607, year = {2020}, author = {Han, X and Tomaszewski, EJ and Sorwat, J and Pan, Y and Kappler, A and Byrne, JM}, title = {Effect of Microbial Biomass and Humic Acids on Abiotic and Biotic Magnetite Formation.}, journal = {Environmental science & technology}, volume = {54}, number = {7}, pages = {4121-4130}, doi = {10.1021/acs.est.9b07095}, pmid = {32129607}, issn = {1520-5851}, mesh = {Biomass ; *Ferric Compounds ; Ferrosoferric Oxide ; *Humic Substances ; Minerals ; Oxidation-Reduction ; }, abstract = {Magnetite (Fe3O4) is an environmentally ubiquitous mixed-valent iron (Fe) mineral, which can form via biotic or abiotic transformation of Fe(III) (oxyhydr)oxides such as ferrihydrite (Fh). It is currently unclear whether environmentally relevant biogenic Fh from Fe(II)-oxidizing bacteria, containing cell-derived organic matter, can transform to magnetite. We compared abiotic and biotic transformation: (1) abiogenic Fh (aFh); (2) abiogenic Fh coprecipitated with humic acids (aFh-HA); (3) biogenic Fh produced by phototrophic Fe(II)-oxidizer Rhodobacter ferrooxidans SW2 (bFh); and (4) biogenic Fh treated with bleach to remove biogenic organic matter (bFh-bleach). Abiotic or biotic transformation of Fh was promoted by Feaq[2+] or Fe(III)-reducing bacteria. Feaq[2+]-catalyzed abiotic reaction with aFh and bFh-bleach led to complete transformation to magnetite. In contrast, aFh-HA only partially (68%) transformed to magnetite, and bFh (17%) transformed to goethite. We hypothesize that microbial biomass stabilized bFh against reaction with Feaq[2+]. All four Fh substrates were transformed into magnetite during biotic reduction, suggesting that Fh remains bioavailable even when associated with microbial biomass. Additionally, there were poorly ordered magnetic components detected in the biogenic end products for aFh and aFh-HA. Nevertheless, abiotic transformation was much faster than biotic transformation, implying that initial Feaq[2+] concentration, passivation of Fh, and/or sequestration of Fe(II) by bacterial cells and associated biomass play major roles in the rate of magnetite formation from Fh. These results improve our understanding of factors influencing secondary mineralization of Fh in the environment.}, } @article {pmid32122349, year = {2020}, author = {Gray, MW and Burger, G and Derelle, R and Klimeš, V and Leger, MM and Sarrasin, M and Vlček, Č and Roger, AJ and Eliáš, M and Lang, BF}, title = {The draft nuclear genome sequence and predicted mitochondrial proteome of Andalucia godoyi, a protist with the most gene-rich and bacteria-like mitochondrial genome.}, journal = {BMC biology}, volume = {18}, number = {1}, pages = {22}, pmid = {32122349}, issn = {1741-7007}, support = {MOP-4124//CIHR/Canada ; MOP-11212//CIHR/Canada ; }, mesh = {Cell Nucleus/genetics ; Eukaryota/*genetics ; *Genome, Mitochondrial ; Mitochondrial Proteins/*genetics/metabolism ; *Proteome ; }, abstract = {BACKGROUND: Comparative analyses have indicated that the mitochondrion of the last eukaryotic common ancestor likely possessed all the key core structures and functions that are widely conserved throughout the domain Eucarya. To date, such studies have largely focused on animals, fungi, and land plants (primarily multicellular eukaryotes); relatively few mitochondrial proteomes from protists (primarily unicellular eukaryotic microbes) have been examined. To gauge the full extent of mitochondrial structural and functional complexity and to identify potential evolutionary trends in mitochondrial proteomes, more comprehensive explorations of phylogenetically diverse mitochondrial proteomes are required. In this regard, a key group is the jakobids, a clade of protists belonging to the eukaryotic supergroup Discoba, distinguished by having the most gene-rich and most bacteria-like mitochondrial genomes discovered to date.

RESULTS: In this study, we assembled the draft nuclear genome sequence for the jakobid Andalucia godoyi and used a comprehensive in silico approach to infer the nucleus-encoded portion of the mitochondrial proteome of this protist, identifying 864 candidate mitochondrial proteins. The A. godoyi mitochondrial proteome has a complexity that parallels that of other eukaryotes, while exhibiting an unusually large number of ancestral features that have been lost particularly in opisthokont (animal and fungal) mitochondria. Notably, we find no evidence that the A. godoyi nuclear genome has or had a gene encoding a single-subunit, T3/T7 bacteriophage-like RNA polymerase, which functions as the mitochondrial transcriptase in all eukaryotes except the jakobids.

CONCLUSIONS: As genome and mitochondrial proteome data have become more widely available, a strikingly punctuate phylogenetic distribution of different mitochondrial components has been revealed, emphasizing that the pathways of mitochondrial proteome evolution are likely complex and lineage-specific. Unraveling this complexity will require comprehensive comparative analyses of mitochondrial proteomes from a phylogenetically broad range of eukaryotes, especially protists. The systematic in silico approach described here offers a valuable adjunct to direct proteomic analysis (e.g., via mass spectrometry), particularly in cases where the latter approach is constrained by sample limitation or other practical considerations.}, } @article {pmid32118486, year = {2020}, author = {Chen, CY and Nguyen, LT and Paoli, GC and Irwin, PL}, title = {The complex multicellular morphology of the food spoilage bacteria Brochothrix thermosphacta strains isolated from ground chicken.}, journal = {Canadian journal of microbiology}, volume = {66}, number = {4}, pages = {303-312}, doi = {10.1139/cjm-2019-0502}, pmid = {32118486}, issn = {1480-3275}, mesh = {Animals ; Brochothrix/classification/*growth & development/isolation & purification/metabolism ; Chickens/*microbiology ; Culture Media/chemistry/metabolism ; Food Contamination/analysis ; Meat/microbiology ; Temperature ; }, abstract = {Herein we describe a highly structured, filamentous growth phenotype displayed by an isolate of the food spoilage microorganism Brochothrix thermosphacta. The growth morphology of this B. thermosphacta strain (strain BII) was dependent on environmental factors such as the growth media, incubation temperatures, and the inoculum concentration. Inoculation of cultures in highly dilute suspensions resulted in the formation of isolated, tight aggregates resembling fungal growth in liquid media. This same strain also formed stable, mesh-like structures in 6-well tissue culture plates under specific growth conditions. The complex growth phenotype does not appear to be unique to strain BII but was common among B. thermosphacta strains isolated from chicken. Light and electron micrographs showed that the filaments of multiple BII cells can organize into complex, tertiary structures resembling multistranded cables. Time-lapse microscopy was employed to monitor the development of such aggregates over 18 h and revealed growth originating from short filaments into compact ball-like clusters that appeared fuzzy due to protruding filaments or cables. This report is the first to document this complex filamentous growth phenotype in a wild-type bacterial isolate of B. thermosphacta.}, } @article {pmid32118436, year = {2020}, author = {Xu, L and Wang, J}, title = {Curl Flux as a Dynamical Origin of the Bifurcations/Phase Transitions of Nonequilibrium Systems: Cell Fate Decision Making.}, journal = {The journal of physical chemistry. B}, volume = {124}, number = {13}, pages = {2549-2559}, doi = {10.1021/acs.jpcb.9b11998}, pmid = {32118436}, issn = {1520-5207}, mesh = {Cell Differentiation ; *Decision Making ; Entropy ; Thermodynamics ; }, abstract = {The underlying interactions in physical and biological systems often lead to a variety of behaviors and emergent states or phases. Under certain conditions, these phases can be transformed from one to another. The phase transition behaviors can be described by the bifurcation or catastrophe where different stable/unstable states can branch out or meet together with the birth of the new and death of the old states. Despite significant efforts, how the bifurcation and catastrophe actually occur dynamically and the associated mechanisms for nonequilibrium systems are still not very clear. As an example, we study the underlying mechanism of cell differentiation through bifurcations. Cell differentiation is one of the key fate decision-making processes that a cell faces. It is crucial for the development of multicellular organisms. Under induction, gene regulation changes, or stochastic fluctuations, the cell fate decision-making processes can exhibit different types of bifurcations or phase transitions. In order to understand the underlying mechanism, it is crucial to find out where and how the bifurcation occurs. However, this is still largely unknown. In this study, we found that the average of the curl flux as a major component of the driving force for the dynamics in addition to the landscape gradient and the associated entropy production rate both reach maximum near the bifurcation. This indicates that the curl flux and entropy production rate may provide the dynamical and thermodynamic origins of the bifurcation/catastrophe or phase transitions for cell differentiation and this possibly applies to many other nonequilibrium active systems.}, } @article {pmid32117212, year = {2019}, author = {Bonsignore, P and Kuiper, JWP and Adrian, J and Goob, G and Hauck, CR}, title = {CEACAM3-A Prim(at)e Invention for Opsonin-Independent Phagocytosis of Bacteria.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {3160}, pmid = {32117212}, issn = {1664-3224}, mesh = {Animals ; Bacteria/*immunology ; Biological Evolution ; Carcinoembryonic Antigen/*genetics/*immunology ; Humans ; Immunity, Innate/genetics/immunology ; Phagocytosis/*genetics/*immunology ; Primates ; }, abstract = {Phagocytosis is one of the key innate defense mechanisms executed by specialized cells in multicellular animals. Recent evidence suggests that a particular phagocytic receptor expressed by human polymorphonuclear granulocytes, the carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3), is one of the fastest-evolving human proteins. In this focused review, we will try to resolve the conundrum why a conserved process such as phagocytosis is conducted by a rapidly changing receptor. Therefore, we will first summarize the biochemical and structural details of this immunoglobulin-related glycoprotein in the context of the human CEACAM family. The function of CEACAM3 for the efficient, opsonin-independent detection and phagocytosis of highly specialized, host-restricted bacteria will be further elaborated. Taking into account the decisive role of CEACAM3 in the interaction with pathogenic bacteria, we will discuss the evolutionary trajectory of the CEACAM3 gene within the primate lineage and highlight the consequences of CEACAM3 polymorphisms in human populations. From a synopsis of these studies, CEACAM3 emerges as an important component of human innate immunity and a prominent example of a dedicated receptor for professional phagocytosis.}, } @article {pmid32115438, year = {2020}, author = {Urayama, SI and Takaki, Y and Hagiwara, D and Nunoura, T}, title = {dsRNA-seq Reveals Novel RNA Virus and Virus-Like Putative Complete Genome Sequences from Hymeniacidon sp. Sponge.}, journal = {Microbes and environments}, volume = {35}, number = {2}, pages = {}, pmid = {32115438}, issn = {1347-4405}, mesh = {Animals ; Aquatic Organisms/virology ; *Genome, Viral ; Phylogeny ; Porifera/*virology ; RNA Viruses/*classification/isolation & purification ; RNA, Double-Stranded/*genetics ; RNA, Viral/genetics ; RNA-Seq ; Sequence Analysis, DNA ; }, abstract = {Invertebrates are a source of previously unknown RNA viruses that fill gaps in the viral phylogenetic tree. Although limited information is currently available on RNA viral diversity in the marine sponge, a primordial multicellular animal that belongs to the phylum Porifera, the marine sponge is one of the well-studied holobiont systems. In the present study, we elucidated the putative complete genome sequences of five novel RNA viruses from Hymeniacidon sponge using a combination of double-stranded RNA sequencing, called fragmented and primer ligated dsRNA sequencing, and a conventional transcriptome method targeting single-stranded RNA. We identified highly diverged RNA-dependent RNA polymerase sequences, including a potential novel RNA viral lineage, in the sponge and three viruses presumed to infect sponge cells.}, } @article {pmid32109395, year = {2020}, author = {Tan, Y and Barnbrook, M and Wilson, Y and Molnár, A and Bukys, A and Hudson, A}, title = {Shared Mutations in a Novel Glutaredoxin Repressor of Multicellular Trichome Fate Underlie Parallel Evolution of Antirrhinum Species.}, journal = {Current biology : CB}, volume = {30}, number = {8}, pages = {1357-1366.e4}, doi = {10.1016/j.cub.2020.01.060}, pmid = {32109395}, issn = {1879-0445}, support = {BB/J01446X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Antirrhinum/*genetics/growth & development ; *Biological Evolution ; Glutaredoxins/antagonists & inhibitors/*genetics ; Mutation ; Plant Proteins/antagonists & inhibitors/*genetics ; Trichomes/genetics/*growth & development ; }, abstract = {Most angiosperms produce trichomes-epidermal hairs that have protective or more specialized roles. Trichomes are multicellular in almost all species and, in the majority, secretory. Despite the importance of multicellular trichomes for plant protection and as a source of high-value products, the mechanisms that control their development are only poorly understood. Here, we investigate the control of multicellular trichome patterns using natural variation within the genus Antirrhinum (snapdragons), which has evolved hairy alpine-adapted species or lowland species with a restricted trichome pattern multiple times in parallel. We find that a single gene, Hairy (H), which is needed to repress trichome fate, underlies variation in trichome patterns between all Antirrhinum species except one. We show that H encodes a novel epidermis-specific glutaredoxin and that the pattern of trichome distribution within individuals reflects the location of H expression. Phylogenetic and functional tests suggest that H gained its trichome-repressing role late in the history of eudicots and that the ancestral Antirrhinum had an active H gene and restricted trichome distribution. Loss of H function was involved in an early divergence of alpine and lowland Antirrhinum lineages, and the alleles underlying this split were later reused in parallel evolution of alpines from lowland ancestors, and vice versa. We also find evidence for an evolutionary reversal from a widespread to restricted trichome distribution involving a suppressor mutation and for a pleiotropic effect of H on plant growth that might constrain the evolution of trichome pattern.}, } @article {pmid32102937, year = {2020}, author = {Elliott, L and Moore, I and Kirchhelle, C}, title = {Spatio-temporal control of post-Golgi exocytic trafficking in plants.}, journal = {Journal of cell science}, volume = {133}, number = {4}, pages = {}, doi = {10.1242/jcs.237065}, pmid = {32102937}, issn = {1477-9137}, support = {BB/P01979X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Eukaryotic Cells/metabolism ; *Golgi Apparatus/metabolism ; *Plants/metabolism ; Protein Transport ; rab GTP-Binding Proteins/metabolism ; }, abstract = {A complex and dynamic endomembrane system is a hallmark of eukaryotic cells and underpins the evolution of specialised cell types in multicellular organisms. Endomembrane system function critically depends on the ability of the cell to (1) define compartment and pathway identity, and (2) organise compartments and pathways dynamically in space and time. Eukaryotes possess a complex molecular machinery to control these processes, including small GTPases and their regulators, SNAREs, tethering factors, motor proteins, and cytoskeletal elements. Whereas many of the core components of the eukaryotic endomembrane system are broadly conserved, there have been substantial diversifications within different lineages, possibly reflecting lineage-specific requirements of endomembrane trafficking. This Review focusses on the spatio-temporal regulation of post-Golgi exocytic transport in plants. It highlights recent advances in our understanding of the elaborate network of pathways transporting different cargoes to different domains of the cell surface, and the molecular machinery underpinning them (with a focus on Rab GTPases, their interactors and the cytoskeleton). We primarily focus on transport in the context of growth, but also highlight how these pathways are co-opted during plant immunity responses and at the plant-pathogen interface.}, } @article {pmid32101166, year = {2020}, author = {Kaur, G and Burroughs, AM and Iyer, LM and Aravind, L}, title = {Highly regulated, diversifying NTP-dependent biological conflict systems with implications for the emergence of multicellularity.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32101166}, issn = {2050-084X}, mesh = {ATPases Associated with Diverse Cellular Activities/metabolism ; Archaea/*cytology/genetics/metabolism ; Bacteria/*cytology/genetics/metabolism ; Biological Evolution ; CRISPR-Cas Systems ; Nucleotides/*metabolism ; Prokaryotic Cells ; }, abstract = {Social cellular aggregation or multicellular organization pose increased risk of transmission of infections through the system upon infection of a single cell. The generality of the evolutionary responses to this outside of Metazoa remains unclear. We report the discovery of several thematically unified, remarkable biological conflict systems preponderantly present in multicellular prokaryotes. These combine thresholding mechanisms utilizing NTPase chaperones (the MoxR-vWA couple), GTPases and proteolytic cascades with hypervariable effectors, which vary either by using a reverse transcriptase-dependent diversity-generating system or through a system of acquisition of diverse protein modules, typically in inactive form, from various cellular subsystems. Conciliant lines of evidence indicate their deployment against invasive entities, like viruses, to limit their spread in multicellular/social contexts via physical containment, dominant-negative interactions or apoptosis. These findings argue for both a similar operational 'grammar' and shared protein domains in the sensing and limiting of infections during the multiple emergences of multicellularity.}, } @article {pmid32097591, year = {2020}, author = {Greyson-Gaito, CJ and Bartley, TJ and Cottenie, K and Jarvis, WMC and Newman, AEM and Stothart, MR}, title = {Into the wild: microbiome transplant studies need broader ecological reality.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1921}, pages = {20192834}, pmid = {32097591}, issn = {1471-2954}, mesh = {Ecology ; Gastrointestinal Microbiome ; *Microbiota ; *Symbiosis ; }, abstract = {Gut microbial communities (microbiomes) profoundly shape the ecology and evolution of multicellular life. Interactions between host and microbiome appear to be reciprocal, and ecological theory is now being applied to better understand how hosts and their microbiome influence each other. However, some ecological processes that underlie reciprocal host-microbiome interactions may be obscured by the current convention of highly controlled transplantation experiments. Although these approaches have yielded invaluable insights, there is a need for a broader array of approaches to fully understand host-microbiome reciprocity. Using a directed review, we surveyed the breadth of ecological reality in the current literature on gut microbiome transplants with non-human recipients. For 55 studies, we categorized nine key experimental conditions that impact the ecological reality (EcoReality) of the transplant, including host taxon match and donor environment. Using these categories, we rated the EcoReality of each transplant. Encouragingly, the breadth of EcoReality has increased over time, but some components of EcoReality are still relatively unexplored, including recipient host environment and microbiome state. The conceptual framework we develop here maps the landscape of possible EcoReality to highlight where fundamental ecological processes can be considered in future transplant experiments.}, } @article {pmid32095969, year = {2020}, author = {Moody, LA}, title = {Three-dimensional growth: a developmental innovation that facilitated plant terrestrialization.}, journal = {Journal of plant research}, volume = {133}, number = {3}, pages = {283-290}, pmid = {32095969}, issn = {1618-0860}, support = {University Research Fellowship//Royal Society/ ; BB/M020517/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Chlorophyta/classification/*growth & development ; Embryophyta/classification/*growth & development ; Flowers ; Phaeophyta/classification/growth & development ; *Phylogeny ; Plant Roots ; }, abstract = {One of the most transformative events in the history of life on earth was the transition of plants from water to land approximately 470 million years ago. Within the Charophyte green algae, the closest living relatives of land plants, body plans have evolved from those that comprise simple unicells to those that are morphologically complex, large and multicellular. The Charophytes developed these broad ranging body plans by exploiting a range of one-dimensional and two-dimensional growth strategies to produce filaments, mats and branches. When plants were confronted with harsh conditions on land, they were required to make significant changes to the way they shaped their body plans. One of the fundamental developmental transitions that occurred was the evolution of three-dimensional growth and the acquisition of apical cells with three or more cutting faces. Plants subsequently developed a range of morphological adaptations (e.g. vasculature, roots, flowers, seeds) that enabled them to colonise progressively drier environments. 3D apical growth also evolved convergently in the brown algae, completely independently of the green lineage. This review summarises the evolving developmental complexities observed in the early divergent Charophytes all the way through to the earliest conquerors of land, and investigates 3D apical growth in the brown algae.}, } @article {pmid32094536, year = {2020}, author = {Tang, Q and Pang, K and Yuan, X and Xiao, S}, title = {A one-billion-year-old multicellular chlorophyte.}, journal = {Nature ecology & evolution}, volume = {4}, number = {4}, pages = {543-549}, pmid = {32094536}, issn = {2397-334X}, support = {80NSSC18K1086/ImNASA/Intramural NASA/United States ; }, mesh = {*Diatoms ; *Ecosystem ; Fossils ; Phylogeny ; }, abstract = {Chlorophytes (representing a clade within the Viridiplantae and a sister group of the Streptophyta) probably dominated marine export bioproductivity and played a key role in facilitating ecosystem complexity before the Mesozoic diversification of phototrophic eukaryotes such as diatoms, coccolithophorans and dinoflagellates. Molecular clock and biomarker data indicate that chlorophytes diverged in the Mesoproterozoic or early Neoproterozoic, followed by their subsequent phylogenetic diversification, multicellular evolution and ecological expansion in the late Neoproterozoic and Palaeozoic. This model, however, has not been rigorously tested with palaeontological data because of the scarcity of Proterozoic chlorophyte fossils. Here we report abundant millimetre-sized, multicellular and morphologically differentiated macrofossils from rocks approximately 1,000 million years ago. These fossils are described as Proterocladus antiquus new species and are interpreted as benthic siphonocladalean chlorophytes, suggesting that chlorophytes acquired macroscopic size, multicellularity and cellular differentiation nearly a billion years ago, much earlier than previously thought.}, } @article {pmid32094163, year = {2020}, author = {Yahalomi, D and Atkinson, SD and Neuhof, M and Chang, ES and Philippe, H and Cartwright, P and Bartholomew, JL and Huchon, D}, title = {A cnidarian parasite of salmon (Myxozoa: Henneguya) lacks a mitochondrial genome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {10}, pages = {5358-5363}, pmid = {32094163}, issn = {1091-6490}, mesh = {Animals ; *Genome, Mitochondrial ; *Host-Parasite Interactions ; Myxozoa/*classification/*genetics ; Phylogeny ; Salmon/*parasitology ; }, abstract = {Although aerobic respiration is a hallmark of eukaryotes, a few unicellular lineages, growing in hypoxic environments, have secondarily lost this ability. In the absence of oxygen, the mitochondria of these organisms have lost all or parts of their genomes and evolved into mitochondria-related organelles (MROs). There has been debate regarding the presence of MROs in animals. Using deep sequencing approaches, we discovered that a member of the Cnidaria, the myxozoan Henneguya salminicola, has no mitochondrial genome, and thus has lost the ability to perform aerobic cellular respiration. This indicates that these core eukaryotic features are not ubiquitous among animals. Our analyses suggest that H. salminicola lost not only its mitochondrial genome but also nearly all nuclear genes involved in transcription and replication of the mitochondrial genome. In contrast, we identified many genes that encode proteins involved in other mitochondrial pathways and determined that genes involved in aerobic respiration or mitochondrial DNA replication were either absent or present only as pseudogenes. As a control, we used the same sequencing and annotation methods to show that a closely related myxozoan, Myxobolus squamalis, has a mitochondrial genome. The molecular results are supported by fluorescence micrographs, which show the presence of mitochondrial DNA in M. squamalis, but not in H. salminicola. Our discovery confirms that adaptation to an anaerobic environment is not unique to single-celled eukaryotes, but has also evolved in a multicellular, parasitic animal. Hence, H. salminicola provides an opportunity for understanding the evolutionary transition from an aerobic to an exclusive anaerobic metabolism.}, } @article {pmid32084159, year = {2020}, author = {Finoshin, AD and Adameyko, KI and Mikhailov, KV and Kravchuk, OI and Georgiev, AA and Gornostaev, NG and Kosevich, IA and Mikhailov, VS and Gazizova, GR and Shagimardanova, EI and Gusev, OA and Lyupina, YV}, title = {Iron metabolic pathways in the processes of sponge plasticity.}, journal = {PloS one}, volume = {15}, number = {2}, pages = {e0228722}, pmid = {32084159}, issn = {1932-6203}, mesh = {Animals ; Computational Biology ; Gene Expression Profiling ; Iron/*metabolism ; Iron-Regulatory Proteins/genetics/metabolism ; Molecular Sequence Annotation ; Phylogeny ; Porifera/genetics/*metabolism ; RNA-Seq ; }, abstract = {The ability to regulate oxygen consumption evolved in ancestral animals and is intrinsically linked to iron metabolism. The iron pathways have been intensively studied in mammals, whereas data on distant invertebrates are limited. Sea sponges represent the oldest animal phylum and have unique structural plasticity and capacity to reaggregate after complete dissociation. We studied iron metabolic factors and their expression during reaggregation in the White Sea cold-water sponges Halichondria panicea and Halisarca dujardini. De novo transcriptomes were assembled using RNA-Seq data, and evolutionary trends were analyzed with bioinformatic tools. Differential expression during reaggregation was studied for H. dujardini. Enzymes of the heme biosynthesis pathway and transport globins, neuroglobin (NGB) and androglobin (ADGB), were identified in sponges. The globins mutate at higher evolutionary rates than the heme synthesis enzymes. Highly conserved iron-regulatory protein 1 (IRP1) presumably interacts with the iron-responsive elements (IREs) found in mRNAs of ferritin (FTH1) and a putative transferrin receptor NAALAD2. The reaggregation process is accompanied by increased expression of IRP1, the antiapoptotic factor BCL2, the inflammation factor NFκB (p65), FTH1 and NGB, as well as by an increase in mitochondrial density. Our data indicate a complex mechanism of iron regulation in sponge structural plasticity and help to better understand general mechanisms of morphogenetic processes in multicellular species.}, } @article {pmid32079678, year = {2020}, author = {Erwin, DH}, title = {The origin of animal body plans: a view from fossil evidence and the regulatory genome.}, journal = {Development (Cambridge, England)}, volume = {147}, number = {4}, pages = {}, doi = {10.1242/dev.182899}, pmid = {32079678}, issn = {1477-9129}, mesh = {Animals ; Biological Evolution ; *Body Patterning ; Cell Differentiation ; Embryo, Nonmammalian ; *Fossils ; Gene Regulatory Networks ; *Genome ; Genomics ; Invertebrates/classification ; Paleontology ; Phylogeny ; *Regulatory Sequences, Nucleic Acid ; Sequence Analysis, RNA ; }, abstract = {The origins and the early evolution of multicellular animals required the exploitation of holozoan genomic regulatory elements and the acquisition of new regulatory tools. Comparative studies of metazoans and their relatives now allow reconstruction of the evolution of the metazoan regulatory genome, but the deep conservation of many genes has led to varied hypotheses about the morphology of early animals and the extent of developmental co-option. In this Review, I assess the emerging view that the early diversification of animals involved small organisms with diverse cell types, but largely lacking complex developmental patterning, which evolved independently in different bilaterian clades during the Cambrian Explosion.}, } @article {pmid32078984, year = {2020}, author = {Moreau, CS}, title = {Symbioses among ants and microbes.}, journal = {Current opinion in insect science}, volume = {39}, number = {}, pages = {1-5}, doi = {10.1016/j.cois.2020.01.002}, pmid = {32078984}, issn = {2214-5753}, mesh = {Animals ; *Ants/microbiology/parasitology ; Bacteria ; Behavior ; Diet ; Fungi ; Gastrointestinal Microbiome ; Host-Parasite Interactions ; Microbiota ; Nematoda ; *Symbiosis ; Trematoda ; Viruses ; }, abstract = {Ants have been shown to engage in symbiosis across the tree of life, although our knowledge is far from complete. These interactions range from mutualistic to parasitic with several instances of manipulation of host behavior. Nutrient contributions in these symbioses include both farming for food and nitrogen recycling by gut-associated microbes. Interestingly, the ants that are mostly likely to host diverse and likely functional gut microbial communities are those that feed on extreme diets. Although we do see many instances of symbiosis between ants and microbes, there are also examples of species without a functional gut microbiome. Symbiosis among microbes and eukaryotic hosts is common and often considered a hallmark of multicellular evolution [1]. This is true among many of the over 13000 species of ants, although symbiosis between ants and microbes are not ubiquitous. These microbial-ant symbiotic interactions span the tree of life and include microbial eukaryotes, fungi, viruses, and bacteria. These interactions range from pathogenic to mutualistic, with many relationships still not well understood. Although our knowledge of the diversity of these microbes in ants is growing rapidly, and in some cases we know the function and interaction with the host, we still have much to learn about - the little things that run the little things that run the world!}, } @article {pmid32076502, year = {2020}, author = {Noh, S and Christopher, L and Strassmann, JE and Queller, DC}, title = {Wild Dictyostelium discoideum social amoebae show plastic responses to the presence of nonrelatives during multicellular development.}, journal = {Ecology and evolution}, volume = {10}, number = {3}, pages = {1119-1134}, pmid = {32076502}, issn = {2045-7758}, abstract = {When multiple strains of microbes form social groups, such as the multicellular fruiting bodies of Dictyostelium discoideum, conflict can arise regarding cell fate. Both fixed and plastic differences among strains can contribute to cell fate, and plastic responses may be particularly important if social environments frequently change. We used RNA-sequencing and photographic time series analysis to detect possible conflict-induced plastic differences between wild D. discoideum aggregates formed by single strains compared with mixed pairs of strains (chimeras). We found one hundred and two differentially expressed genes that were enriched for biological processes including cytoskeleton organization and cyclic AMP response (up-regulated in chimeras), and DNA replication and cell cycle (down-regulated in chimeras). In addition, our data indicate that in reference to a time series of multicellular development in the laboratory strain AX4, chimeras may be slightly behind clonal aggregates in their development. Finally, phenotypic analysis supported slower splitting of aggregates and a nonsignificant trend for larger group sizes in chimeras. The transcriptomic comparison and phenotypic analyses support discoordination among aggregate group members due to social conflict. These results are consistent with previously observed factors that affect cell fate decision in D. discoideum and provide evidence for plasticity in cAMP signaling and phenotypic coordination during development in response to social conflict in D. discoideum and similar microbial social groups.}, } @article {pmid32075388, year = {2020}, author = {Raudenská, M and Svobodová, M and Gumulec, J and Falk, M and Masařík, M}, title = {The Importance of Cancer-Associated Fibroblasts in the Pathogenesis of Head and Neck Cancers.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {33}, number = {1}, pages = {39-48}, doi = {10.14735/amko202039}, pmid = {32075388}, issn = {1802-5307}, mesh = {*Cancer-Associated Fibroblasts ; Head and Neck Neoplasms/*pathology ; Humans ; Phenotype ; }, abstract = {BACKGROUND: Despite progress in anticancer therapies, head and neck squamous cell carcinoma (HNSCC) has still a low survival rate. Recent studies have shown that tumour stroma may play an important role in the pathogenesis of this malignant disease. Fibroblasts are a major component of the tumour microenvironment and may significantly influence HNSCC progression as indicated by the contribution they make to important hallmarks of cancer, such as inflammation, non-restricted growth, angiogenesis, invasion, metastasis, and therapy resistance. It is well known that tumour cells can confer a cancer-associated fibroblast (CAF) phenotype that supports the growth and dissemination of cancer cells. CAFs can stimulate cancer progression through cell-cell contacts and communication, remodelling of extracellular matrix, and production of many signal molecules and matrix metalloproteinases. Consequently, genetic changes in epithelial cells are probably not the only factor that drives HNSCC carcinogenesis. Non-genetic changes in the tumour stroma can also be significantly involved. Stress-induced signals can induce a multicellular program, creating a field of tissue that is predisposed to malignant transformation. The “field cancerization” concept represents a process of active evolution of intercellular interactions and feedback loops between tumour and stromal cells. This model paves the way to study cancer from a new perspective and identify new therapeutic targets.

PURPOSE: In this review, we discuss current knowledge about CAFs, such as their cellular origin, phenotypical plasticity and functional heterogeneity, and stress their contribution to HNSCC progression. This article was supported by the project AZV 16-29835A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 18. 6. 2019 Accepted: 9. 9. 2019.}, } @article {pmid32072723, year = {2020}, author = {Kulanthaivelu, K and Bhat, MD and Prasad, C and Srinivas, D and Mhatre, R and Nandeesh, BN}, title = {Brain MRI Findings in Coenurosis: A Helminth Infection.}, journal = {Journal of neuroimaging : official journal of the American Society of Neuroimaging}, volume = {30}, number = {3}, pages = {359-369}, doi = {10.1111/jon.12696}, pmid = {32072723}, issn = {1552-6569}, mesh = {Adult ; Aged ; Brain/*diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Magnetic Resonance Spectroscopy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neurocysticercosis/complications/*diagnostic imaging ; Neuroimaging ; Retrospective Studies ; Seizures/*diagnostic imaging/etiology ; }, abstract = {BACKGROUND AND PURPOSE: Parasitic neuroinfections in humans have etiological agents spanning a broad spectrum from unicellular (protozoan) to multicellular helminthic (metazoan) organisms. Cerebral coenurosis is a rare cestodal helminthic infection caused by Taenia multiceps. The neuroimaging features of this entity were reviewed to discern an imaging phenotype.

METHODS: Retrospective analysis was performed on 6 cases of cerebral coenurosis, whose diagnoses were confirmed by histopathology. The clinical, imaging, and histopathological features were recorded for analysis.

RESULTS: Clinical expressions included focal neurological deficit due to mass effect (n = 4), intraventricular obstruction with features of raised intracranial tension (n = 1), headache (n = 3), seizures (n = 3), and incidental lesions (n = 1). One patient presented with recurrence 1 year after surgical excision. Neuroimaging revealed cystic thin-walled lesions with clustered eccentric internal nodules corresponding to the plenitude of protoscolices of the tapeworm. Three of the lesions showed a multilocular cystic morphology. Spectroscopic metabolite signature of alanine and succinate commensurate with the parasitic etiology was remarkable in the lesions. Enhancement and edema inversely correlated with the signal suppression on fluid-attenuated inversion recovery (FLAIR) imaging. The lesions had a predominantly juxtacortical distribution.

CONCLUSIONS: In an appropriate clinical setting, a cystic lesion with clustered eccentric internal nodular foci ought to raise the suspicion of this rare infection. Magnetic resonance spectroscopic signature of succinate and alanine, if present, further strengthens the likelihood of coenurosis. Signal characteristics, wall enhancement, and perilesional edema may vary, possibly determined by the stage in the evolution of the parasite.}, } @article {pmid32067938, year = {2020}, author = {Agosti, A and Marchesi, S and Scita, G and Ciarletta, P}, title = {Modelling cancer cell budding in-vitro as a self-organised, non-equilibrium growth process.}, journal = {Journal of theoretical biology}, volume = {492}, number = {}, pages = {110203}, doi = {10.1016/j.jtbi.2020.110203}, pmid = {32067938}, issn = {1095-8541}, mesh = {Cell Adhesion ; Cell Division ; Humans ; Mechanical Phenomena ; Models, Theoretical ; *Neoplasms ; }, abstract = {Tissue self-organization into defined and well-controlled three-dimensional structures is essential during development for the generation of organs. A similar, but highly deranged process might also occur during the aberrant growth of cancers, which frequently display a loss of the orderly structures of the tissue of origin, but retain a multicellular organization in the form of spheroids, strands, and buds. The latter structures are often seen when tumors masses switch to an invasive behavior into surrounding tissues. However, the general physical principles governing the self-organized architectures of tumor cell populations remain by and large unclear. In this work, we perform in-vitro experiments to characterize the growth properties of glioblastoma budding emerging from monolayers. We further propose a theoretical model and its finite element implementation to characterize such a topological transition, that is modelled as a self-organised, non-equilibrium phenomenon driven by the trade-off of mechanical forces and physical interactions exerted at cell-cell and cell-substrate adhesions. Notably, the unstable disorder states of uncontrolled cellular proliferation macroscopically emerge as complex spatio-temporal patterns that evolve statistically correlated by a universal law.}, } @article {pmid32061941, year = {2020}, author = {Lamrabet, O and Jauslin, T and Lima, WC and Leippe, M and Cosson, P}, title = {The multifarious lysozyme arsenal of Dictyostelium discoideum.}, journal = {Developmental and comparative immunology}, volume = {107}, number = {}, pages = {103645}, doi = {10.1016/j.dci.2020.103645}, pmid = {32061941}, issn = {1879-0089}, mesh = {Animals ; Bacteria ; Dictyostelium/*physiology ; Ion Channels/genetics/metabolism ; Muramidase/genetics/*metabolism ; Phagocytes/*immunology ; Phylogeny ; Pore Forming Cytotoxic Proteins/genetics/metabolism ; Protozoan Proteins/genetics/metabolism ; }, abstract = {Dictyostelium discoideum is a free-living soil amoeba which feeds upon bacteria. To bind, ingest, and kill bacteria, D. discoideum uses molecular mechanisms analogous to those found in professional phagocytic cells of multicellular organisms. D. discoideum is equipped with a large arsenal of antimicrobial peptides and proteins including amoebapore-like peptides and lysozymes. This review describes the family of lysozymes in D. discoideum. We identified 22 genes potentially encoding four different types of lysozymes in the D. discoideum genome. Although most of these genes are also present in the genomes of other amoebal species, no other organism is as well-equipped with lysozyme genes as D. discoideum.}, } @article {pmid32061337, year = {2020}, author = {Ishibashi, K and Tanaka, Y and Morishita, Y}, title = {Perspectives on the evolution of aquaporin superfamily.}, journal = {Vitamins and hormones}, volume = {112}, number = {}, pages = {1-27}, doi = {10.1016/bs.vh.2019.08.001}, pmid = {32061337}, issn = {0083-6729}, mesh = {Amino Acid Sequence ; *Aquaporins/genetics/metabolism ; *Phylogeny ; Water ; }, abstract = {Aquaporins (AQPs) belong to a transmembrane protein superfamily composed of an internal repeat of a three membrane-spanning domain and each has a highly conserved NPA box. Based on the more variable carboxyl-terminal NPA box, AQPs can be divided into three subfamilies: (1) glycerol-channel aquaglyceroporin (gAQP) (2) water-selective AQP (wAQP), and (3) deviated superaquaporin (sAQP) in the order of passible evolution. This classification has functional and localization relevance: most wAQPs transports water selectively whereas gAQPs and sAQPs also transport small molecules with sAQPs mostly localized inside the cell. As this classification is not based on the function, some wAQPs functioning as glycerol channels will not be included in gAQPs. AQP ancestors may have first originated in eubacteria as gAQPs to transport small molecules such as glycerol. Later some of them may have acquired a water-selective filter to become wAQPs. Although AQPs are absent in many bacteria, especially in archaea, both gAQPs and wAQPs may have been carried over to eukaryotes or horizontally transferred. Finally, multicellular organisms have obtained new sAQPs, which are curiously absent in fungi and plants. Interestingly, both plants and higher insects independently have lost gAQPs, whose functions, however, have been taken over by functionally modified wAQPs partly obtained by horizontal gene transfers from bacteria. This evolutionary viewpoints on AQPs will facilitate further functional analysis of AQP-like sequences and expand our viewpoints on AQP superfamily.}, } @article {pmid32053788, year = {2020}, author = {Prior, KF and Rijo-Ferreira, F and Assis, PA and Hirako, IC and Weaver, DR and Gazzinelli, RT and Reece, SE}, title = {Periodic Parasites and Daily Host Rhythms.}, journal = {Cell host & microbe}, volume = {27}, number = {2}, pages = {176-187}, pmid = {32053788}, issn = {1934-6069}, support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; R21 AI131632/AI/NIAID NIH HHS/United States ; U19 AI089681/AI/NIAID NIH HHS/United States ; R21 AI150546/AI/NIAID NIH HHS/United States ; R21 NS103180/NS/NINDS NIH HHS/United States ; R01 AI079293/AI/NIAID NIH HHS/United States ; R01 NS098747/NS/NINDS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Biological Evolution ; Circadian Clocks/physiology ; Circadian Rhythm/*physiology ; Erythrocytes/parasitology ; Host-Parasite Interactions/*physiology ; Humans ; Immunity/physiology ; Inflammation/parasitology ; Malaria ; Mice ; Mosquito Vectors/parasitology/physiology ; Parasites/physiology ; Plasmodium/*physiology ; }, abstract = {Biological rhythms appear to be an elegant solution to the challenge of coordinating activities with the consequences of the Earth's daily and seasonal rotation. The genes and molecular mechanisms underpinning circadian clocks in multicellular organisms are well understood. In contrast, the regulatory mechanisms and fitness consequences of biological rhythms exhibited by parasites remain mysterious. Here, we explore how periodicity in parasite traits is generated and why daily rhythms matter for parasite fitness. We focus on malaria (Plasmodium) parasites which exhibit developmental rhythms during replication in the mammalian host's blood and in transmission to vectors. Rhythmic in-host parasite replication is responsible for eliciting inflammatory responses, the severity of disease symptoms, and fueling transmission, as well as conferring tolerance to anti-parasite drugs. Thus, understanding both how and why the timing and synchrony of parasites are connected to the daily rhythms of hosts and vectors may make treatment more effective and less toxic to hosts.}, } @article {pmid32045589, year = {2020}, author = {Duan, H and Ni, S and Yang, S and Zhou, Y and Zhang, Y and Zhang, S}, title = {Conservation of eATP perception throughout multicellular animal evolution: Identification and functional characterization of coral and amphioxus P2X7-like receptors and flounder P2X7 receptor.}, journal = {Developmental and comparative immunology}, volume = {106}, number = {}, pages = {103641}, doi = {10.1016/j.dci.2020.103641}, pmid = {32045589}, issn = {1879-0089}, mesh = {Adenosine Triphosphate/*metabolism ; Alarmins/immunology ; Animals ; Anthozoa/*physiology ; Biological Evolution ; Conserved Sequence/*genetics ; Cytokines/metabolism ; Extracellular Space/*metabolism ; Flounder/*physiology ; Humans ; Inflammation Mediators/metabolism ; Lancelets/*physiology ; Mammals ; Phagocytosis ; Receptors, Purinergic P2X7/*genetics/metabolism ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Signal Transduction ; }, abstract = {Perception of extracellular ATP (eATP), a common endogenous damage-associated molecular pattern, is through its receptor P2X7R. If eATP/P2X7R signaling is conserved throughout animal evolution is unknown. Moreover, little information is currently available regarding P2X7R in invertebrates. Here we demonstrated that the coral P2X7-like receptor, AdP2X7RL, the amphioxus P2X7-like receptor, BjP2X7RL and the flounder P2X7 receptor, PoP2X7R, shared common features characteristic of mammalian P2X7R, and their 3D structures displayed high resemblance to that of human P2X7R. Expression of Adp2x7rl, Bjp2x7rl and Pop2x7r was all subjected to the regulation by LPS and ATP. We also showed that AdP2X7RL, BjP2X7RL and PoP2X7R were distributed on the plasma membrane in AdP2X7RL-, BjP2X7RL- and PoP2X7R-expressing HEK cells, and had strong affinity to eATP. Importantly, the binding of AdP2X7RL, BjP2X7RL and PoP2X7R to eATP all induced similar downstream responses, including induction of cytokines (IL-1β, IL-6, IL-8 and CCL-2), enhancement of phagocytosis and activation of AKT/ERK-associated signaling pathway observed for mammalian P2X7R. Collectively, our results indicate for the first time that both coral and amphioxus P2X7RL as well as flounder P2X7R can interact with eATP, and induce events that trigger mammalian mechanisms, suggesting the high conservation of eATP perception throughout multicellular animal evolution.}, } @article {pmid32044287, year = {2020}, author = {Kuwabara, T and Igarashi, K}, title = {Thermotogales origin scenario of eukaryogenesis.}, journal = {Journal of theoretical biology}, volume = {492}, number = {}, pages = {110192}, doi = {10.1016/j.jtbi.2020.110192}, pmid = {32044287}, issn = {1095-8541}, mesh = {*Archaea/genetics ; Bacteria/genetics ; Biological Evolution ; *Eukaryota/genetics ; Eukaryotic Cells ; Evolution, Molecular ; Phylogeny ; }, abstract = {How eukaryotes were generated is an enigma of evolutionary biology. Widely accepted archaeal-origin eukaryogenesis scenarios, based on similarities of genes and related characteristics between archaea and eukaryotes, cannot explain several eukaryote-specific features of the last eukaryotic common ancestor, such as glycerol-3-phosphate-type membrane lipids, large cells and genomes, and endomembrane formation. Thermotogales spheroids, having multicopy-integrated large nucleoids and producing progeny in periplasm, may explain all of these features as well as endoplasmic reticulum-type signal cleavage sites, although they cannot divide. We hypothesize that the progeny chromosome is formed by random joining small DNAs in immature progeny, followed by reorganization by mechanisms including homologous recombination enabled with multicopy-integrated large genome (MILG). We propose that Thermotogales ancestor spheroids came to divide owing to the archaeal cell division genes horizontally transferred via virus-related particles, forming the first eukaryotic common ancestor (FECA). Referring to the hypothesis, the archaeal information-processing system would have been established in FECA by random joining DNAs excised from the MILG, which contained horizontally transferred archaeal and bacterial DNAs, followed by reorganization by the MILG-enabled homologous recombination. Thus, the large genome may have been a prerequisite, but not a consequence, of eukaryogenesis. The random joining of DNAs likely provided the basic mechanisms for eukaryotic evolution: producing the diversity by the formations of supergroups, novel genes, and introns that are involved in exon shuffling.}, } @article {pmid32042121, year = {2020}, author = {Black, AJ and Bourrat, P and Rainey, PB}, title = {Ecological scaffolding and the evolution of individuality.}, journal = {Nature ecology & evolution}, volume = {4}, number = {3}, pages = {426-436}, pmid = {32042121}, issn = {2397-334X}, mesh = {*Biological Evolution ; Ecology ; Reproduction ; *Selection, Genetic ; }, abstract = {Evolutionary transitions in individuality are central to the emergence of biological complexity. Recent experiments provide glimpses of processes underpinning the transition from single cells to multicellular life and draw attention to the critical role of ecology. Here, we emphasize this ecological dimension and argue that its current absence from theoretical frameworks hampers development of general explanatory solutions. Using mechanistic mathematical models, we show how a minimal ecological structure comprising patchily distributed resources and between-patch dispersal can scaffold Darwinian-like properties on collectives of cells. This scaffolding causes cells to participate directly in the process of evolution by natural selection as if they were members of multicellular collectives, with collectives participating in a death-birth process arising from the interplay between the timing of dispersal events and the rate of resource use by cells. When this timescale is sufficiently long and new collectives are founded by single cells, collectives experience conditions that favour evolution of a reproductive division of labour. Together our simple model makes explicit key events in the major evolutionary transition to multicellularity. It also makes predictions concerning the life history of certain pathogens and serves as an ecological recipe for experimental realization of evolutionary transitions.}, } @article {pmid32039188, year = {2020}, author = {Li, R and Hornberger, K and Dutton, JR and Hubel, A}, title = {Cryopreservation of Human iPS Cell Aggregates in a DMSO-Free Solution-An Optimization and Comparative Study.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {8}, number = {}, pages = {1}, pmid = {32039188}, issn = {2296-4185}, support = {R01 EB023880/EB/NIBIB NIH HHS/United States ; }, abstract = {Human induced pluripotent stem cells (hiPSCs) are an important cell source for regenerative medicine products. Effective methods of preservation are critical to their clinical and commercial applications. The use of a dimethyl sulfoxide (DMSO)-free solution containing all non-toxic molecules offers an effective alternative to the conventional DMSO and alleviates pain points associated with the use of DMSO in the cryopreservation of hiPSCs. Both hiPSCs and cells differentiated from them are commonly multicellular systems, which are more sensitive to stresses of freezing and thawing than single cells. In this investigation, low-temperature Raman spectroscopy visualized freezing behaviors of hiPSC aggregates in different solutions. These aggregates exhibited sensitivity to undercooling in DMSO-containing solutions. We demonstrated the ability to replace DMSO with non-toxic molecules, improve post-thaw cell survival, and reduce sensitivity to undercooling. An accelerated optimization process capitalized on the positive synergy among multiple DMSO-free molecules, which acted in concert to influence ice formation and protect cells during freezing and thawing. A differential evolution algorithm was used to optimize the multi-variable, DMSO-free preservation protocol in 8 experiments. hiPSC aggregates frozen in the optimized solution did not exhibit the same sensitivity to undercooling as those frozen in non-optimized solutions or DMSO, indicating superior adaptability of the optimized solution to different freezing modalities and unplanned deviations. This investigation shows the importance of optimization, explains the mechanisms and advantages of a DMSO-free solution, and enables not only improved cryopreservation of hiPSCs but potentially other cell types for translational regenerative medicine.}, } @article {pmid32032743, year = {2020}, author = {Dokanehiifard, S and Soltani, BM and Ghiasi, P and Baharvand, H and Reza Ganjali, M and Hosseinkhani, S}, title = {hsa-miR-766-5p as a new regulator of mitochondrial apoptosis pathway for discriminating of cell death from cardiac differentiation.}, journal = {Gene}, volume = {736}, number = {}, pages = {144448}, doi = {10.1016/j.gene.2020.144448}, pmid = {32032743}, issn = {1879-0038}, mesh = {Apoptosis/*genetics ; Cell Death/*genetics ; Cell Differentiation/*genetics ; Cell Line ; Computational Biology/methods ; Down-Regulation/genetics ; HEK293 Cells ; Human Embryonic Stem Cells/physiology ; Humans ; MicroRNAs/*genetics ; Mitochondria/*genetics ; Myocytes, Cardiac/*physiology ; }, abstract = {Dispose of unnecessary cells in multicellular organism take place through apoptosis as a mode of programmed cell death (PCD). This process is triggered through two main pathway including extrinsic pathway or death receptor pathway and intrinsic or mitochondrial pathway. An alternative role for mitochondrial pathway of cell death is its involvement in cell differentiation. Biochemistry of cell differentiation indicates a common origin for differentiation and apoptosis. miRNAs are a group of small non coding mediator RNAs in regulation of many routes such as apoptosis and differentiation. By using bioinformatics tools hsa-miR-766-5p was predicted to target the BAX, BAK and BOK genes involved in mitochondrial apoptosis pathway. RT-qPCR and dual luciferase assay showed targeting of BAX, BAK and BOK 3'UTRs via hsa-miR-766, detected in SW480 and HEK293T cell lines. Caspases 3/7 and 9 activity assay revealed the involvement of hsa-miR-766-5p in mitochondrial apoptosis pathway regulation detected following overexpression and downregulation of this miRNA, detected in SW480 cells treated with 1 μM doxorubicin. Flow cytometry and MTT assay indicated cell death reduction and viability elevation effect of hsa-miR-766 in SW480 cells after its overexpression. Endogenous expression of hsa-miR-766 during the course of human embryonic stem cells (hESCs) differentiation into cardiomyocytes revealed an inverse expression status of this miRNA with BOK. However, the expression of this miRNA was inversely related to BAX and BAK for some time points of differentiation. Overall this results show the involvement of hsa-miR-766 in regulation of mitochondrial apoptosis pathway.}, } @article {pmid32027371, year = {2020}, author = {Posada, D}, title = {CellCoal: Coalescent Simulation of Single-Cell Sequencing Samples.}, journal = {Molecular biology and evolution}, volume = {37}, number = {5}, pages = {1535-1542}, pmid = {32027371}, issn = {1537-1719}, support = {617457/ERC_/European Research Council/International ; }, mesh = {Evolution, Molecular ; *Genetic Techniques ; *Genotype ; Sequence Analysis, DNA ; *Single-Cell Analysis ; *Software ; }, abstract = {Our capacity to study individual cells has enabled a new level of resolution for understanding complex biological systems such as multicellular organisms or microbial communities. Not surprisingly, several methods have been developed in recent years with a formidable potential to investigate the somatic evolution of single cells in both healthy and pathological tissues. However, single-cell sequencing data can be quite noisy due to different technical biases, so inferences resulting from these new methods need to be carefully contrasted. Here, I introduce CellCoal, a software tool for the coalescent simulation of single-cell sequencing genotypes. CellCoal simulates the history of single-cell samples obtained from somatic cell populations with different demographic histories and produces single-nucleotide variants under a variety of mutation models, sequencing read counts, and genotype likelihoods, considering allelic imbalance, allelic dropout, amplification, and sequencing errors, typical of this type of data. CellCoal is a flexible tool that can be used to understand the implications of different somatic evolutionary processes at the single-cell level, and to benchmark dedicated bioinformatic tools for the analysis of single-cell sequencing data. CellCoal is available at https://github.com/dapogon/cellcoal.}, } @article {pmid32024776, year = {2020}, author = {Munke, A and Kimura, K and Tomaru, Y and Okamoto, K}, title = {Capsid Structure of a Marine Algal Virus of the Order Picornavirales.}, journal = {Journal of virology}, volume = {94}, number = {9}, pages = {}, pmid = {32024776}, issn = {1098-5514}, mesh = {Capsid/chemistry ; Capsid Proteins/*genetics/metabolism/*ultrastructure ; Cryoelectron Microscopy/methods ; Diatoms/metabolism/*virology ; Genome, Viral/genetics ; Phycodnaviridae/genetics ; Picornaviridae/metabolism/ultrastructure ; RNA Viruses/genetics ; Virion/genetics ; }, abstract = {The order Picornavirales includes viruses that infect different kinds of eukaryotes and that share similar properties. The capsid proteins (CPs) of viruses in the order that infect unicellular organisms, such as algae, presumably possess certain characteristics that have changed little over the course of evolution, and thus these viruses may resemble the Picornavirales ancestor in some respects. Herein, we present the capsid structure of Chaetoceros tenuissimus RNA virus type II (CtenRNAV-II) determined using cryo-electron microscopy at a resolution of 3.1 Å, the first alga virus belonging to the family Marnaviridae of the order Picornavirales A structural comparison to related invertebrate and vertebrate viruses revealed a unique surface loop of the major CP VP1 that had not been observed previously, and further, revealed that another VP1 loop obscures the so-called canyon, which is a host-receptor binding site for many of the mammalian Picornavirales viruses. VP2 has an N-terminal tail, which has previously been reported as a primordial feature of Picornavirales viruses. The above-mentioned and other critical structural features provide new insights on three long-standing theories about Picornavirales: (i) the canyon hypothesis, (ii) the primordial VP2 domain swap, and (iii) the hypothesis that alga Picornavirales viruses could share characteristics with the Picornavirales ancestor.IMPORTANCE Identifying the acquired structural traits in virus capsids is important for elucidating what functions are essential among viruses that infect different hosts. The Picornavirales viruses infect a broad spectrum of hosts, ranging from unicellular algae to insects and mammals and include many human pathogens. Those viruses that infect unicellular protists, such as algae, are likely to have undergone fewer structural changes during the course of evolution compared to those viruses that infect multicellular eukaryotes and thus still share some characteristics with the Picornavirales ancestor. This article describes the first atomic capsid structure of an alga Marnavirus, CtenRNAV-II. A comparison to capsid structures of the related invertebrate and vertebrate viruses identified a number of structural traits that have been functionally acquired or lost during the course of evolution. These observations provide new insights on past theories on the viability and evolution of Picornavirales viruses.}, } @article {pmid32020592, year = {2020}, author = {Nishino, J and Watanabe, S and Miya, F and Kamatani, T and Sugawara, T and Boroevich, KA and Tsunoda, T}, title = {Quantification of multicellular colonization in tumor metastasis using exome-sequencing data.}, journal = {International journal of cancer}, volume = {146}, number = {9}, pages = {2488-2497}, pmid = {32020592}, issn = {1097-0215}, mesh = {Biomarkers, Tumor/*genetics ; Cohort Studies ; Colorectal Neoplasms/*genetics/*pathology ; *DNA Copy Number Variations ; Exome/*genetics ; Gene Expression Regulation, Neoplastic ; Humans ; *Mutation ; Neoplasm Metastasis ; Prognosis ; Exome Sequencing/*methods ; }, abstract = {Metastasis is a major cause of cancer-related mortality, and it is essential to understand how metastasis occurs in order to overcome it. One relevant question is the origin of a metastatic tumor cell population. Although the hypothesis of a single-cell origin for metastasis from a primary tumor has long been prevalent, several recent studies using mouse models have supported a multicellular origin of metastasis. Human bulk whole-exome sequencing (WES) studies also have demonstrated a multiple "clonal" origin of metastasis, with different mutational compositions. Specifically, there has not yet been strong research to determine how many founder cells colonize a metastatic tumor. To address this question, under the metastatic model of "single bottleneck followed by rapid growth," we developed a method to quantify the "founder cell population size" in a metastasis using paired WES data from primary and metachronous metastatic tumors. Simulation studies demonstrated the proposed method gives unbiased results with sufficient accuracy in the range of realistic settings. Applying the proposed method to real WES data from four colorectal cancer patients, all samples supported a multicellular origin of metastasis and the founder size was quantified, ranging from 3 to 17 cells. Such a wide-range of founder sizes estimated by the proposed method suggests that there are large variations in genetic similarity between primary and metastatic tumors in the same subjects, which may explain the observed (dis)similarity of drug responses between tumors.}, } @article {pmid32019441, year = {2020}, author = {Carmel, Y and Shavit, A}, title = {Operationalizing evolutionary transitions in individuality.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1920}, pages = {20192805}, pmid = {32019441}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; *Individuality ; Reproduction ; }, abstract = {Evolutionary transitions in individuality (hereafter, ETIs), such as the transition to multi-cellularity and the transition to social colonies, have been at the centre of evolutionary research, but only few attempts were made to systematically operationalize this concept. Here, we devise a set of four indicators intended to assess the change in complexity during ETIs: system size, inseparability, reproductive specialization and non-reproductive specialization. We then conduct a quantitative comparison across multiple taxa and ETIs. Our analysis reveals that inseparability has a crucial role in the process; it seems irreversible and may mark the point where a group of individuals becomes a new individual at a higher hierarchical level. Interestingly, we find that disparate groups demonstrate a similar pattern of progression along ETIs.}, } @article {pmid32016363, year = {2020}, author = {Alsufyani, T and Califano, G and Deicke, M and Grueneberg, J and Weiss, A and Engelen, AH and Kwantes, M and Mohr, JF and Ulrich, JF and Wichard, T}, title = {Macroalgal-bacterial interactions: identification and role of thallusin in morphogenesis of the seaweed Ulva (Chlorophyta).}, journal = {Journal of experimental botany}, volume = {71}, number = {11}, pages = {3340-3349}, pmid = {32016363}, issn = {1460-2431}, mesh = {Bacteria ; *Chlorophyta ; Morphogenesis ; Pyridines ; *Seaweed ; *Ulva ; }, abstract = {Macroalgal microbiomes have core functions related to biofilm formation, growth, and morphogenesis of seaweeds. In particular, the growth and development of the sea lettuce Ulva spp. (Chlorophyta) depend on bacteria releasing morphogenetic compounds. Under axenic conditions, the macroalga Ulva mutabilis develops a callus-like phenotype with cell wall protrusions. However, co-culturing with Roseovarius sp. (MS2) and Maribacter sp. (MS6), which produce various stimulatory chemical mediators, completely recovers morphogenesis. This ecological reconstruction forms a tripartite community which can be further studied for its role in cross-kingdom interactions. Hence, our study sought to identify algal growth- and morphogenesis-promoting factors (AGMPFs) capable of phenocopying the activity of Maribacter spp. We performed bioassay-guided solid-phase extraction in water samples collected from U. mutabilis aquaculture systems. We uncovered novel ecophysiological functions of thallusin, a sesquiterpenoid morphogen, identified for the first time in algal aquaculture. Thallusin, released by Maribacter sp., induced rhizoid and cell wall formation at a concentration of 11 pmol l-1. We demonstrated that gametes acquired the iron complex of thallusin, thereby linking morphogenetic processes with intracellular iron homeostasis. Understanding macroalgae-bacteria interactions permits further elucidation of the evolution of multicellularity and cellular differentiation, and development of new applications in microbiome-mediated aquaculture systems.}, } @article {pmid34692062, year = {2020}, author = {Lin, W and Kirschvink, JL and Paterson, GA and Bazylinski, DA and Pan, Y}, title = {On the origin of microbial magnetoreception.}, journal = {National science review}, volume = {7}, number = {2}, pages = {472-479}, pmid = {34692062}, issn = {2053-714X}, abstract = {A broad range of organisms, from prokaryotes to higher animals, have the ability to sense and utilize Earth's geomagnetic field-a behavior known as magnetoreception. Although our knowledge of the physiological mechanisms of magnetoreception has increased substantially over recent decades, the origin of this behavior remains a fundamental question in evolutionary biology. Despite this, there is growing evidence that magnetic iron mineral biosynthesis by prokaryotes may represent the earliest form of biogenic magnetic sensors on Earth. Here, we integrate new data from microbiology, geology and nanotechnology, and propose that initial biomineralization of intracellular iron nanoparticles in early life evolved as a mechanism for mitigating the toxicity of reactive oxygen species (ROS), as ultraviolet radiation and free-iron-generated ROS would have been a major environmental challenge for life on early Earth. This iron-based system could have later been co-opted as a magnetic sensor for magnetoreception in microorganisms, suggesting an origin of microbial magnetoreception as the result of the evolutionary process of exaptation.}, } @article {pmid32003151, year = {2020}, author = {Rimskaya-Korsakova, N and Dyachuk, V and Temereva, E}, title = {Parapodial glandular organs in Owenia borealis (Annelida: Oweniidae) and their possible relationship with nephridia.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {334}, number = {2}, pages = {88-99}, doi = {10.1002/jez.b.22928}, pmid = {32003151}, issn = {1552-5015}, mesh = {Animals ; Annelida/*anatomy & histology/physiology ; Microscopy, Electron, Transmission ; Urinary Tract/anatomy & histology/ultrastructure ; }, abstract = {Oweniidae is a basal group of recent annelids and nowadays it attracts the attention of researchers of many biological fields. Surprisingly, details of their anatomy, like the adult excretory system, remain obscure. Researchers recently suggested that the paired organs of tubeworms in the family Oweniidae are related to nephridia. In the current study of Owenia borealis adults, we determined that these structures are parapodial glandular organs (PGOs) and are located in the first two segments of adults. The PGOs are complex subepidermal multicellular glands that contain secretory cells, that is, goblet cells, which are differentiated by the type of the producing tube matter. The goblet cells are surrounded by muscles that are used to extrude material stored in the PGO's lumen into the external environment. The anterior pair of PGOs have very well-developed rough endoplasmatic reticulum in the proximal cells, spacious Golgi complexes, numerous nail-shaped microvilli, and apocrine secretory processes in the goblet cells of the distal parts. The posterior pair of PGOs only consists of cells, which probably produce proteinaceous fibrils. We discuss the homology of goblet cells with specific nail-shaped microvilli that produce β-chitin within annelids. We also discuss the possibility that PGOs and nephridia have a common origin. This study provides new information on the ultrastructure of cells that secrete the organic material used to form the tubes inhabited by tube-dwelling annelids.}, } @article {pmid31983537, year = {2020}, author = {Yao, M and Ventura, PB and Jiang, Y and Rodriguez, FJ and Wang, L and Perry, JSA and Yang, Y and Wahl, K and Crittenden, RB and Bennett, ML and Qi, L and Gong, CC and Li, XN and Barres, BA and Bender, TP and Ravichandran, KS and Janes, KA and Eberhart, CG and Zong, H}, title = {Astrocytic trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth.}, journal = {Cell}, volume = {180}, number = {3}, pages = {502-520.e19}, pmid = {31983537}, issn = {1097-4172}, support = {R00 CA237728/CA/NCI NIH HHS/United States ; R01 NS055089/NS/NINDS NIH HHS/United States ; P30 CA044579/CA/NCI NIH HHS/United States ; U01 CA215794/CA/NCI NIH HHS/United States ; K99 CA237728/CA/NCI NIH HHS/United States ; T32 HD007348/HD/NICHD NIH HHS/United States ; R21 HL143025/HL/NHLBI NIH HHS/United States ; F31 NS076313/NS/NINDS NIH HHS/United States ; R01 NS097271/NS/NINDS NIH HHS/United States ; T32 CA009109/CA/NCI NIH HHS/United States ; R01 CA194470/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Astrocytes/*metabolism ; Carcinogenesis/*metabolism ; Cell Lineage ; *Cell Transdifferentiation ; Cerebellar Neoplasms/*metabolism/pathology ; Disease Models, Animal ; Female ; Hedgehog Proteins/metabolism ; Heterografts ; Humans ; Insulin-Like Growth Factor I/genetics/metabolism ; Interleukin-4/genetics/metabolism ; Male ; Medulloblastoma/*metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/metabolism ; *Paracrine Communication ; Tumor Microenvironment ; }, abstract = {The tumor microenvironment (TME) is critical for tumor progression. However, the establishment and function of the TME remain obscure because of its complex cellular composition. Using a mouse genetic system called mosaic analysis with double markers (MADMs), we delineated TME evolution at single-cell resolution in sonic hedgehog (SHH)-activated medulloblastomas that originate from unipotent granule neuron progenitors in the brain. First, we found that astrocytes within the TME (TuAstrocytes) were trans-differentiated from tumor granule neuron precursors (GNPs), which normally never differentiate into astrocytes. Second, we identified that TME-derived IGF1 promotes tumor progression. Third, we uncovered that insulin-like growth factor 1 (IGF1) is produced by tumor-associated microglia in response to interleukin-4 (IL-4) stimulation. Finally, we found that IL-4 is secreted by TuAstrocytes. Collectively, our studies reveal an evolutionary process that produces a multi-lateral network within the TME of medulloblastoma: a fraction of tumor cells trans-differentiate into TuAstrocytes, which, in turn, produce IL-4 that stimulates microglia to produce IGF1 to promote tumor progression.}, } @article {pmid31982725, year = {2020}, author = {Bissoli, I and Muscari, C}, title = {Doxorubicin and α-Mangostin oppositely affect luminal breast cancer cell stemness evaluated by a new retinaldehyde-dependent ALDH assay in MCF-7 tumor spheroids.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {124}, number = {}, pages = {109927}, doi = {10.1016/j.biopha.2020.109927}, pmid = {31982725}, issn = {1950-6007}, mesh = {Aldehyde Dehydrogenase/metabolism ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/pharmacology ; Breast Neoplasms/*drug therapy/pathology ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Doxorubicin/administration & dosage/*pharmacology ; Female ; Humans ; Inhibitory Concentration 50 ; MCF-7 Cells ; Neoplastic Stem Cells/*drug effects ; Retinaldehyde/metabolism ; Spheroids, Cellular/drug effects/metabolism ; Xanthones/administration & dosage/*pharmacology ; }, abstract = {According to cancer stem cell theory, only a limited number of self-renewing and cloning cells are responsible for tumor relapse after a period of remittance. The aim of the present study was to investigate the effects of Doxorubicin and α-Mangostin, two antiproliferative drugs, on both tumor bulk and stem cells in multicellular tumor spheroids originated from the luminal MCF-7 breast cancer cell line. A new and original fluorimetric assay was used to selectively measure the activity of the retinaldehyde-dependent isoenzymes of aldehyde dehydrogenase (RALDH), which are markers of a subpopulation of breast cancer stem cells. The administration of 5 μg/ml (12.2 μM) α-Mangostin for 48 h provoked: i) a marked disaggregation of the spheroids, leading to a doubling of their volume (p < 0.01), ii) a 40 % decrease in cell viability (p < 0.01), evaluated by the acid phosphatase assay, and iii) a reduction by more than 90 % of RALDH activity. By contrast, Doxorubicin given for 48 h in the range of 0.1-40 μM did not significantly reduce cell viability and caused only a modest modification of the spheroid morphology. Moreover, 40 μM Doxorubicin increased RALDH activity 2.5-fold compared to the untreated sample. When the two drugs were administered together using 5 μg/ml α-Mangostin, the IC50 of Doxorubicin referred to cell viability decreased six-fold and the RALDH activity was further reduced. In conclusion, the combined administration of Doxorubicin and α-Mangostin provoked a significant cytotoxicity and a remarkable inhibition of RALDH activity in MCF-7 tumor spheroids, suggesting that these drugs could be effective in reducing cell stemness in luminal breast cancer.}, } @article {pmid31975241, year = {2020}, author = {Puzakov, MV and Puzakova, LV and Cheresiz, SV}, title = {The Tc1-like elements with the spliceosomal introns in mollusk genomes.}, journal = {Molecular genetics and genomics : MGG}, volume = {295}, number = {3}, pages = {621-633}, doi = {10.1007/s00438-020-01645-1}, pmid = {31975241}, issn = {1617-4623}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; *DNA Transposable Elements ; Evolution, Molecular ; *Genome ; *Introns ; Mollusca/*genetics ; *Phylogeny ; RNA Splicing/*genetics ; Sequence Homology ; Transposases/*genetics ; }, abstract = {Transposable elements (TEs) are DNA sequences capable of transpositions within the genome and thus exerting a considerable influence on the genome functioning and structure and serving as a source of new genes. TE biodiversity studies in previously unexplored species are important for the fundamental understanding of the TE influence on eukaryotic genomes. TEs are classified into retrotransposons and DNA transposons. IS630/Tc1/mariner (ITm) superfamily of DNA transposons is one of the most diverse groups broadly represented among the eukaryotes. The study of 19 mollusk genomes revealed a new group of ITm superfamily elements, which we henceforth refer to as TLEWI. These TEs are characterized by the low copy number, the lack of terminal inverted repeats, the catalytic domain with DD36E signature and the presence of spliceosomal introns in transposase coding sequence. Their prevalence among the mollusks is limited to the class Bivalvia. Since TLEWI possess the features of domesticated TE and structures similar to the eukaryotic genes which are not typical for the DNA transposons, we consider the hypothesis of co-optation of TLEWI gene by the bivalves. The results of our study will fill the gap of knowledge about the prevalence, activity, and evolution of the ITm DNA transposons in multicellular genomes and will facilitate our understanding of the mechanisms of TE domestication by the host genome.}, } @article {pmid31973071, year = {2020}, author = {Auboeuf, D}, title = {Physicochemical Foundations of Life that Direct Evolution: Chance and Natural Selection are not Evolutionary Driving Forces.}, journal = {Life (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {31973071}, issn = {2075-1729}, support = {Salary//Institut National de la Santé et de la Recherche Médicale/ ; }, abstract = {The current framework of evolutionary theory postulates that evolution relies on random mutations generating a diversity of phenotypes on which natural selection acts. This framework was established using a top-down approach as it originated from Darwinism, which is based on observations made of complex multicellular organisms and, then, modified to fit a DNA-centric view. In this article, it is argued that based on a bottom-up approach starting from the physicochemical properties of nucleic and amino acid polymers, we should reject the facts that (i) natural selection plays a dominant role in evolution and (ii) the probability of mutations is independent of the generated phenotype. It is shown that the adaptation of a phenotype to an environment does not correspond to organism fitness, but rather corresponds to maintaining the genome stability and integrity. In a stable environment, the phenotype maintains the stability of its originating genome and both (genome and phenotype) are reproduced identically. In an unstable environment (i.e., corresponding to variations in physicochemical parameters above a physiological range), the phenotype no longer maintains the stability of its originating genome, but instead influences its variations. Indeed, environment- and cellular-dependent physicochemical parameters define the probability of mutations in terms of frequency, nature, and location in a genome. Evolution is non-deterministic because it relies on probabilistic physicochemical rules, and evolution is driven by a bidirectional interplay between genome and phenotype in which the phenotype ensures the stability of its originating genome in a cellular and environmental physicochemical parameter-depending manner.}, } @article {pmid31971511, year = {2020}, author = {Narasimhan, M and Johnson, A and Prizak, R and Kaufmann, WA and Tan, S and Casillas-Pérez, B and Friml, J}, title = {Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {31971511}, issn = {2050-084X}, support = {I 3630/FWF_/Austrian Science Fund FWF/Austria ; ALTF 723-2015//European Molecular Biology Organization/ ; 742985//H2020 European Research Council/ ; I3630B25//Austrian Science Fund/ ; }, mesh = {*Arabidopsis/genetics/metabolism/physiology ; Biological Evolution ; *Clathrin/chemistry/metabolism/ultrastructure ; Clathrin-Coated Vesicles/chemistry/metabolism/ultrastructure ; *Coated Pits, Cell-Membrane/chemistry/metabolism/ultrastructure ; Endocytosis/*physiology ; Microscopy, Electron ; Models, Biological ; }, abstract = {In plants, clathrin mediated endocytosis (CME) represents the major route for cargo internalisation from the cell surface. It has been assumed to operate in an evolutionary conserved manner as in yeast and animals. Here we report characterisation of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement in electron microscopy and quantitative live imaging techniques. Arabidopsis CME appears to follow the constant curvature model and the bona fide CME population generates vesicles of a predominantly hexagonal-basket type; larger and with faster kinetics than in other models. Contrary to the existing paradigm, actin is dispensable for CME events at the plasma membrane but plays a unique role in collecting endocytic vesicles, sorting of internalised cargos and directional endosome movement that itself actively promote CME events. Internalized vesicles display a strongly delayed and sequential uncoating. These unique features highlight the independent evolution of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes.}, } @article {pmid31967577, year = {2020}, author = {Cockell, CS and Osinski, G and Sapers, H and Pontefract, A and Parnell, J}, title = {Microbial Life in Impact Craters.}, journal = {Current issues in molecular biology}, volume = {38}, number = {}, pages = {75-102}, doi = {10.21775/cimb.038.075}, pmid = {31967577}, issn = {1467-3045}, mesh = {Bacteria/*isolation & purification/radiation effects/ultrastructure ; Caves/*microbiology ; *Earth, Planet ; Environment ; *Environmental Microbiology ; Evolution, Planetary ; Geologic Sediments/*microbiology ; Geological Phenomena ; Geology/*history ; History, Ancient ; Meteoroids ; Microbiota/*radiation effects ; Minor Planets ; Temperature ; }, abstract = {Asteroid and comet impacts are known to have caused profound disruption to multicellular life, yet their influence on habitats for microorganisms, which comprise the majority of Earth's biomass, is less well understood. Of particular interest are geological changes in the target lithology at and near the point of impact that can persist for billions of years. Deep subsurface and surface-dwelling microorganisms are shown to gain advantages from impact-induced fracturing of rocks. Deleterious changes are associated with impact-induced closure of pore spaces in rocks. Superimposed on these long-term geological changes are post-impact alterations such as changes in the hydrological system in and around a crater. The close coupling between geological changes and the conditions for microorganisms yields a synthesis of the fields of microbiology and impact cratering. We use these data to discuss how craters can be used in the search for life beyond Earth.}, } @article {pmid31965986, year = {2020}, author = {Reddy, PC and Pradhan, SJ and Karmodiya, K and Galande, S}, title = {Origin of RNA Polymerase II pause in eumetazoans: Insights from Hydra.}, journal = {Journal of biosciences}, volume = {45}, number = {}, pages = {}, pmid = {31965986}, issn = {0973-7138}, support = {//Wellcome Trust/United Kingdom ; IA/E/16/1/503057/WTDBT_/DBT-Wellcome Trust India Alliance/India ; }, mesh = {Animals ; Chromatin/*genetics/ultrastructure ; *Evolution, Molecular ; Gene Expression Regulation/genetics ; High-Throughput Nucleotide Sequencing ; Histones/genetics ; Humans ; Hydra/*genetics ; Mice ; Promoter Regions, Genetic ; RNA Polymerase II/*genetics ; Transcriptome/genetics ; }, abstract = {Multicellular organisms have evolved sophisticated mechanisms for responding to various developmental, environmental and physical stimuli by regulating transcription. The correlation of distribution of RNA Polymerase II (RNA Pol II) with transcription is well established in higher metazoans, however genome-wide information about its distribution in early metazoans, such as Hydra, is virtually absent. To gain insights into RNA Pol II-mediated transcription and chromatin organization in Hydra, we performed chromatin immunoprecipitation (ChIP)-coupled high-throughput sequencing (ChIP-seq) for RNA Pol II and Histone H3. Strikingly, we found that Hydra RNA Pol II is uniformly distributed across the entire gene body, as opposed to its counterparts in bilaterians such as human and mouse. Furthermore, correlation with transcriptome data revealed that the levels of RNA Pol II correlate with the magnitude of gene expression. Strikingly, the characteristic peak of RNA Pol II pause typically observed in bilaterians at the transcription start sites (TSSs) was not observed in Hydra. The RNA Pol II traversing ratio in Hydra was found to be intermediate to yeast and bilaterians. The search for factors involved in RNA Pol II pause revealed that RNA Pol II pausing machinery was most likely acquired first in Cnidaria. However, only a small subset of genes exhibited the promoter proximal RNP Pol II pause. Interestingly, the nucleosome occupancy is highest over the subset of paused genes as compared to total Hydra genes, which is another indication of paused RNA Pol II at these genes. Thus, this study provides evidence for the molecular basis of RNA Pol II pause early during the evolution of multicellular organisms.}, } @article {pmid31959809, year = {2020}, author = {Oña, L and Lachmann, M}, title = {Signalling architectures can prevent cancer evolution.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {674}, pmid = {31959809}, issn = {2045-2322}, mesh = {Animals ; *Biological Evolution ; Cell Division ; Humans ; Models, Theoretical ; Mutation ; Neoplasms/*genetics/*pathology ; Signal Transduction/*physiology ; }, abstract = {Cooperation between cells in multicellular organisms is preserved by an active regulation of growth through the control of cell division. Molecular signals used by cells for tissue growth are usually present during developmental stages, angiogenesis, wound healing and other processes. In this context, the use of molecular signals triggering cell division is a puzzle, because any molecule inducing and aiding growth can be exploited by a cancer cell, disrupting cellular cooperation. A significant difference is that normal cells in a multicellular organism have evolved in competition between high-level organisms to be altruistic, being able to send signals even if it is to their detriment. Conversely, cancer cells evolve their abuse over the cancer's lifespan by out-competing their neighbours. A successful mutation leading to cancer must evolve to be adaptive, enabling a cancer cell to send a signal that results in higher chances to be selected. Using a mathematical model of such molecular signalling mechanism, this paper argues that a signal mechanism would be effective against abuse by cancer if it affects the cell that generates the signal as well as neighbouring cells that would receive a benefit without any cost, resulting in a selective disadvantage for a cancer signalling cell. We find that such molecular signalling mechanisms normally operate in cells as exemplified by growth factors. In scenarios of global and local competition between cells, we calculate how this process affects the fixation probability of a mutant cell generating such a signal, and find that this process can play a key role in limiting the emergence of cancer.}, } @article {pmid31956023, year = {2020}, author = {Bowles, AMC and Bechtold, U and Paps, J}, title = {The Origin of Land Plants Is Rooted in Two Bursts of Genomic Novelty.}, journal = {Current biology : CB}, volume = {30}, number = {3}, pages = {530-536.e2}, doi = {10.1016/j.cub.2019.11.090}, pmid = {31956023}, issn = {1879-0445}, support = {BB/N016831/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Biological Evolution ; Embryophyta/*genetics ; *Evolution, Molecular ; *Genome, Plant ; Phylogeny ; }, abstract = {Over the last 470 Ma, plant evolution has seen major evolutionary transitions, such as the move from water to land and the origins of vascular tissues, seeds, and flowers [1]. These have resulted in the evolution of terrestrial flora that has shaped modern ecosystems and the diversification of the Plant Kingdom, Viridiplantae, into over 374,000 described species [2]. Each of these transitions was accompanied by the gain and loss of genes in plant genomes. For example, whole-genome duplications are known to be fundamental to the origins of both seed and flowering plants [3, 4]. With the ever-increasing quality and quantity of whole-genome data, evolutionary insight into origins of distinct plant groups using comparative genomic techniques is now feasible. Here, using an evolutionary genomics pipeline to compare 208 complete genomes, we analyze the gene content of the ancestral genomes of the last common ancestor of land plants and all other major groups of plant. This approach reveals an unprecedented level of fundamental genomic novelties in two nodes related to the origin of land plants: the first in the origin of streptophytes during the Ediacaran and another in the ancestor of land plants in the Ordovician. Our findings highlight the biological processes that evolved with the origin of land plants and emphasize the importance of conserved gene novelties in plant diversification. Comparisons to other eukaryotic studies suggest a separation of the genomic origins of multicellularity and terrestrialization in plants.}, } @article {pmid31952837, year = {2020}, author = {Rowe, M and Veerus, L and Trosvik, P and Buckling, A and Pizzari, T}, title = {The Reproductive Microbiome: An Emerging Driver of Sexual Selection, Sexual Conflict, Mating Systems, and Reproductive Isolation.}, journal = {Trends in ecology & evolution}, volume = {35}, number = {3}, pages = {220-234}, doi = {10.1016/j.tree.2019.11.004}, pmid = {31952837}, issn = {1872-8383}, mesh = {Animals ; Biological Evolution ; Female ; Male ; *Microbiota ; Reproduction ; *Reproductive Isolation ; Sexual Behavior, Animal ; }, abstract = {All multicellular organisms host microbial communities in and on their bodies, and these microbiomes can have major influences on host biology. Most research has focussed on the oral, skin, and gut microbiomes, whereas relatively little is known about the reproductive microbiome. Here, we review empirical evidence to show that reproductive microbiomes can have significant effects on the reproductive function and performance of males and females. We then discuss the likely repercussions of these effects for evolutionary processes related to sexual selection and sexual conflict, as well as mating systems and reproductive isolation. We argue that knowledge of the reproductive microbiome is fundamental to our understanding of the evolutionary ecology of reproductive strategies and sexual dynamics of host organisms.}, } @article {pmid31943343, year = {2020}, author = {Wang, Y and Wang, F and Hong, DK and Gao, SJ and Wang, R and Wang, JD}, title = {Molecular characterization of DNA methyltransferase 1 and its role in temperature change of armyworm Mythimna separata Walker.}, journal = {Archives of insect biochemistry and physiology}, volume = {103}, number = {4}, pages = {e21651}, doi = {10.1002/arch.21651}, pmid = {31943343}, issn = {1520-6327}, support = {2017J01422//National Key R&D Program of China/ ; CARS-17//Sugar Crop Research System/ ; 31601363//National Natural Science Foundation of China/ ; 2017J01422//Nature Science Foundation of Fujian/ ; }, mesh = {Amino Acid Sequence ; Animals ; Body Temperature ; DNA (Cytosine-5-)-Methyltransferase 1/chemistry/*genetics/metabolism ; Insect Proteins/chemistry/*genetics/metabolism ; Larva/genetics/growth & development/physiology ; Moths/genetics/growth & development/*physiology ; Ovum/growth & development/physiology ; Phylogeny ; Pupa/genetics/growth & development/physiology ; Sequence Alignment ; }, abstract = {DNA methylation refers to the addition of cytosine residues in a CpG context (5'-cytosine-phosphate-guanine-3'). As one of the most common mechanisms of epigenetic modification, it plays a crucial role in regulating gene expression and in a diverse range of biological processes across all multicellular organisms. The relationship between temperature and DNA methylation and how it acts on the adaptability of migratory insects remain unknown. In the present work, a 5,496 bp full-length complementary DNA encoding 1,436 amino acids (named MsDnmt1) was cloned from the devastating migratory pest oriental armyworm, Mythimna separata Walker. The protein shares 36.8-84.4% identity with other insect Dnmt1 isoforms. Spatial and temporal expression analysis revealed that MsDnmt1 was highly expressed in adult stages and head tissue. The changing temperature decreased the expression of MsDnmt1 in both high and low temperature condition. Besides, we found that M. separata exhibited the shortest duration time from the last instar to pupae under 36°C environment when injected with DNA methylation inhibitor. Therefore, our data highlight a potential role for DNA methylation in thermal resistance, which help us to understand the biological role adaptability and colonization of migratory pest in various environments.}, } @article {pmid31942240, year = {2019}, author = {Green, KJ and Jaiganesh, A and Broussard, JA}, title = {Desmosomes: Essential contributors to an integrated intercellular junction network.}, journal = {F1000Research}, volume = {8}, number = {}, pages = {}, pmid = {31942240}, issn = {2046-1402}, support = {K01 AR075087/AR/NIAMS NIH HHS/United States ; R01 AR041836/AR/NIAMS NIH HHS/United States ; R01 CA228196/CA/NCI NIH HHS/United States ; R37 AR043380/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Cytoskeleton/*physiology ; Desmosomes/*physiology ; Intercellular Junctions/*physiology ; Signal Transduction ; }, abstract = {The development of adhesive connections between cells was critical for the evolution of multicellularity and for organizing cells into complex organs with discrete compartments. Four types of intercellular junction are present in vertebrates: desmosomes, adherens junctions, tight junctions, and gap junctions. All are essential for the development of the embryonic layers and organs as well as adult tissue homeostasis. While each junction type is defined as a distinct entity, it is now clear that they cooperate physically and functionally to create a robust and functionally diverse system. During evolution, desmosomes first appeared in vertebrates as highly specialized regions at the plasma membrane that couple the intermediate filament cytoskeleton at points of strong cell-cell adhesion. Here, we review how desmosomes conferred new mechanical and signaling properties to vertebrate cells and tissues through their interactions with the existing junctional and cytoskeletal network.}, } @article {pmid31935413, year = {2020}, author = {Bodmer, WF and Crouch, DJM}, title = {Somatic selection of poorly differentiating variant stem cell clones could be a key to human ageing.}, journal = {Journal of theoretical biology}, volume = {489}, number = {}, pages = {110153}, doi = {10.1016/j.jtbi.2020.110153}, pmid = {31935413}, issn = {1095-8541}, support = {107212/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; 203131/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Aging/genetics ; Biological Evolution ; Cell Differentiation ; Clone Cells ; Humans ; *Stem Cells ; }, abstract = {Any replicating system in which heritable variants with differing replicative potentials can arise is subject to a Darwinian evolutionary process. The continually replicating adult tissue stem cells that control the integrity of many tissues of long-lived, multicellular, complex vertebrate organisms, including humans, constitute such a replicating system. Our suggestion is that somatic selection for mutations (or stable epigenetic changes) that cause an increased rate of adult tissue stem cell proliferation, and their long-term persistence, at the expense of normal differentiation, is a major key to the ageing process. Once an organism has passed the reproductive age, there is no longer any significant counterselection at the organismal level to this inevitable cellular level Darwinian process.}, } @article {pmid31934876, year = {2020}, author = {Tetz, VV and Tetz, GV}, title = {A new biological definition of life.}, journal = {Biomolecular concepts}, volume = {11}, number = {1}, pages = {1-6}, doi = {10.1515/bmc-2020-0001}, pmid = {31934876}, issn = {1868-503X}, mesh = {Biological Evolution ; Genes/*physiology ; Heredity/*genetics ; *Life ; Models, Biological ; Models, Theoretical ; }, abstract = {Here we have proposed a new biological definition of life based on the function and reproduction of existing genes and creation of new ones, which is applicable to both unicellular and multicellular organisms. First, we coined a new term "genetic information metabolism" comprising functioning, reproduction, and creation of genes and their distribution among living and non-living carriers of genetic information. Encompassing this concept, life is defined as organized matter that provides genetic information metabolism. Additionally, we have articulated the general biological function of life as Tetz biological law: "General biological function of life is to provide genetic information metabolism" and formulated novel definition of life: "Life is an organized matter that provides genetic information metabolism". New definition of life and Tetz biological law allow to distinguish in a new way living and non-living objects on Earth and other planets based on providing genetic information metabolism.}, } @article {pmid31932592, year = {2020}, author = {Li, Q and Li, S and Zhang, X and Xu, W and Han, X}, title = {Programmed magnetic manipulation of vesicles into spatially coded prototissue architectures arrays.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {232}, pmid = {31932592}, issn = {2041-1723}, mesh = {Artificial Cells/*chemistry/cytology ; Cell Physiological Phenomena ; *Magnetic Fields ; Osmotic Pressure ; Stainless Steel/chemistry ; Synthetic Biology ; Tissue Engineering/*methods ; Unilamellar Liposomes/*chemistry ; }, abstract = {In nature, cells self-assemble into spatially coded tissular configurations to execute higher-order biological functions as a collective. This mechanism has stimulated the recent trend in synthetic biology to construct tissue-like assemblies from protocell entities, with the aim to understand the evolution mechanism of multicellular mechanisms, create smart materials or devices, and engineer tissue-like biomedical implant. However, the formation of spatially coded and communicating micro-architectures from large quantity of protocell entities, especially for lipid vesicle-based systems that mostly resemble cells, is still challenging. Herein, we magnetically assemble giant unilamellar vesicles (GUVs) or cells into various microstructures with spatially coded configurations and spatialized cascade biochemical reactions using a stainless steel mesh. GUVs in these tissue-like aggregates exhibit uncustomary osmotic stability that cannot be achieved by individual GUVs suspensions. This work provides a versatile and cost-effective strategy to form robust tissue-mimics and indicates a possible superiority of protocell colonies to individual protocells.}, } @article {pmid31928871, year = {2020}, author = {Miller, SR and Longley, R and Hutchins, PR and Bauersachs, T}, title = {Cellular Innovation of the Cyanobacterial Heterocyst by the Adaptive Loss of Plasticity.}, journal = {Current biology : CB}, volume = {30}, number = {2}, pages = {344-350.e4}, doi = {10.1016/j.cub.2019.11.056}, pmid = {31928871}, issn = {1879-0445}, mesh = {*Adaptation, Physiological ; *Biological Evolution ; Cyanobacteria/genetics/*physiology ; Hot Temperature ; Nitrogen Fixation/*physiology ; *Selection, Genetic ; }, abstract = {Cellular innovation is central to biological diversification, yet its underlying mechanisms remain poorly understood [1]. One potential source of new cellular traits is environmentally induced phenotypic variation, or phenotypic plasticity. The plasticity-first hypothesis [2-4] proposes that natural selection can improve upon an ancestrally plastic phenotype to produce a locally adaptive trait, but the role of plasticity for adaptive evolution is still unclear [5-10]. Here, we show that a structurally novel form of the heterocyst, the specialized nitrogen-fixing cell of the multicellular cyanobacterium Fischerella thermalis, has evolved multiple times from ancestrally plastic developmental variation during adaptation to high temperature. Heterocyst glycolipids (HGs) provide an extracellular gas diffusion barrier that protects oxygen-sensitive nitrogenase [11, 12], and cyanobacteria typically exhibit temperature-induced plasticity in HG composition that modulates heterocyst permeability [13, 14]. By contrast, high-temperature specialists of F. thermalis constitutively overproduce glycolipid isomers associated with high temperature to levels unattained by plastic strains. This results in a less-permeable heterocyst, which is advantageous at high temperature but deleterious at low temperature for both nitrogen fixation activity and fitness. Our study illustrates how the origin of a novel cellular phenotype by the genetic assimilation and adaptive refinement of a plastic trait can be a source of biological diversity and contribute to ecological specialization.}, } @article {pmid31921561, year = {2020}, author = {Liang, Z and Geng, Y and Ji, C and Du, H and Wong, CE and Zhang, Q and Zhang, Y and Zhang, P and Riaz, A and Chachar, S and Ding, Y and Wen, J and Wu, Y and Wang, M and Zheng, H and Wu, Y and Demko, V and Shen, L and Han, X and Zhang, P and Gu, X and Yu, H}, title = {Mesostigma viride Genome and Transcriptome Provide Insights into the Origin and Evolution of Streptophyta.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {7}, number = {1}, pages = {1901850}, pmid = {31921561}, issn = {2198-3844}, abstract = {The Streptophyta include unicellular and multicellular charophyte green algae and land plants. Colonization of the terrestrial habitat by land plants is a major evolutionary event that has transformed the planet. So far, lack of genome information on unicellular charophyte algae hinders the understanding of the origin and the evolution from unicellular to multicellular life in Streptophyta. This work reports the high-quality reference genome and transcriptome of Mesostigma viride, a single-celled charophyte alga with a position at the base of Streptophyta. There are abundant segmental duplications and transposable elements in M. viride, which contribute to a relatively large genome with high gene content compared to other algae and early diverging land plants. This work identifies the origin of genetic tools that multicellular Streptophyta have inherited and key genetic innovations required for the evolution of land plants from unicellular aquatic ancestors. The findings shed light on the age-old questions of the evolution of multicellularity and the origin of land plants.}, } @article {pmid31920779, year = {2019}, author = {Levin, M}, title = {The Computational Boundary of a "Self": Developmental Bioelectricity Drives Multicellularity and Scale-Free Cognition.}, journal = {Frontiers in psychology}, volume = {10}, number = {}, pages = {2688}, pmid = {31920779}, issn = {1664-1078}, abstract = {All epistemic agents physically consist of parts that must somehow comprise an integrated cognitive self. Biological individuals consist of subunits (organs, cells, and molecular networks) that are themselves complex and competent in their own native contexts. How do coherent biological Individuals result from the activity of smaller sub-agents? To understand the evolution and function of metazoan creatures' bodies and minds, it is essential to conceptually explore the origin of multicellularity and the scaling of the basal cognition of individual cells into a coherent larger organism. In this article, I synthesize ideas in cognitive science, evolutionary biology, and developmental physiology toward a hypothesis about the origin of Individuality: "Scale-Free Cognition." I propose a fundamental definition of an Individual based on the ability to pursue goals at an appropriate level of scale and organization and suggest a formalism for defining and comparing the cognitive capacities of highly diverse types of agents. Any Self is demarcated by a computational surface - the spatio-temporal boundary of events that it can measure, model, and try to affect. This surface sets a functional boundary - a cognitive "light cone" which defines the scale and limits of its cognition. I hypothesize that higher level goal-directed activity and agency, resulting in larger cognitive boundaries, evolve from the primal homeostatic drive of living things to reduce stress - the difference between current conditions and life-optimal conditions. The mechanisms of developmental bioelectricity - the ability of all cells to form electrical networks that process information - suggest a plausible set of gradual evolutionary steps that naturally lead from physiological homeostasis in single cells to memory, prediction, and ultimately complex cognitive agents, via scale-up of the basic drive of infotaxis. Recent data on the molecular mechanisms of pre-neural bioelectricity suggest a model of how increasingly sophisticated cognitive functions emerge smoothly from cell-cell communication used to guide embryogenesis and regeneration. This set of hypotheses provides a novel perspective on numerous phenomena, such as cancer, and makes several unique, testable predictions for interdisciplinary research that have implications not only for evolutionary developmental biology but also for biomedicine and perhaps artificial intelligence and exobiology.}, } @article {pmid31911467, year = {2020}, author = {Del Cortona, A and Jackson, CJ and Bucchini, F and Van Bel, M and D'hondt, S and Škaloud, P and Delwiche, CF and Knoll, AH and Raven, JA and Verbruggen, H and Vandepoele, K and De Clerck, O and Leliaert, F}, title = {Neoproterozoic origin and multiple transitions to macroscopic growth in green seaweeds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {5}, pages = {2551-2559}, pmid = {31911467}, issn = {1091-6490}, mesh = {Chlorophyta/classification/*growth & development ; Ecosystem ; *Evolution, Molecular ; Phylogeny ; Seaweed/classification/*growth & development ; }, abstract = {The Neoproterozoic Era records the transition from a largely bacterial to a predominantly eukaryotic phototrophic world, creating the foundation for the complex benthic ecosystems that have sustained Metazoa from the Ediacaran Period onward. This study focuses on the evolutionary origins of green seaweeds, which play an important ecological role in the benthos of modern sunlit oceans and likely played a crucial part in the evolution of early animals by structuring benthic habitats and providing novel niches. By applying a phylogenomic approach, we resolve deep relationships of the core Chlorophyta (Ulvophyceae or green seaweeds, and freshwater or terrestrial Chlorophyceae and Trebouxiophyceae) and unveil a rapid radiation of Chlorophyceae and the principal lineages of the Ulvophyceae late in the Neoproterozoic Era. Our time-calibrated tree points to an origin and early diversification of green seaweeds in the late Tonian and Cryogenian periods, an interval marked by two global glaciations with strong consequent changes in the amount of available marine benthic habitat. We hypothesize that unicellular and simple multicellular ancestors of green seaweeds survived these extreme climate events in isolated refugia, and diversified in benthic environments that became increasingly available as ice retreated. An increased supply of nutrients and biotic interactions, such as grazing pressure, likely triggered the independent evolution of macroscopic growth via different strategies, including true multicellularity, and multiple types of giant-celled forms.}, } @article {pmid31883344, year = {2020}, author = {Milocco, L and Salazar-Ciudad, I}, title = {Is evolution predictable? Quantitative genetics under complex genotype-phenotype maps.}, journal = {Evolution; international journal of organic evolution}, volume = {74}, number = {2}, pages = {230-244}, doi = {10.1111/evo.13907}, pmid = {31883344}, issn = {1558-5646}, support = {PGC2018-096802-B-I00//Ministerio de Ciencia, Innovación y Universidades/International ; //Suomalainen Tiedeakatemia/International ; }, mesh = {*Biological Evolution ; *Genetic Variation ; Genetics, Population ; *Genotype ; *Phenotype ; }, abstract = {A fundamental aim of post-genomic 21st century biology is to understand the genotype-phenotype map (GPM) or how specific genetic variation relates to specific phenotypic variation. Quantitative genetics approximates such maps using linear models, and has developed methods to predict the response to selection in a population. The other major field of research concerned with the GPM, developmental evolutionary biology, or evo-devo, has found the GPM to be highly nonlinear and complex. Here, we quantify how the predictions of quantitative genetics are affected by a complex, nonlinear map based on the development of a multicellular organ. We compared the predicted change in mean phenotype for a single generation using the multivariate breeder's equation, with the change observed from the model of development. We found that there are frequent disagreements between predicted and observed responses to selection due to the nonlinear nature of the genotype-phenotype map. Our results are a step toward integrating the fields studying the GPM.}, } @article {pmid31880593, year = {2020}, author = {Wang, DG and Huang, FR and Chen, W and Zhou, Y and Wang, CY and Zhu, F and Shao, BJ and Luo, D}, title = {Clinicopathological Analysis of Acquired Melanocytic Nevi and a Preliminary Study on the Possible Origin of Nevus Cells.}, journal = {The American Journal of dermatopathology}, volume = {42}, number = {6}, pages = {414-422}, doi = {10.1097/DAD.0000000000001599}, pmid = {31880593}, issn = {1533-0311}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers/analysis ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Nevus, Pigmented/*pathology ; Retrospective Studies ; Skin Neoplasms/*pathology ; Stem Cells/*pathology ; Young Adult ; }, abstract = {BACKGROUND: The pathogenesis of acquired melanocytic nevi (AMN) is still unclear, and the origin of nevus cells has not been clarified.

OBJECTIVE: To analyze the clinical features and pathological types of AMN and identify the possible origin of nevus cells.

METHODS: A retrospective study of 2929 cases of AMN was conducted, and 96 specimens of intradermal and junctional nevi were selected. Immunohistochemical assays were performed to detect the expression of basement membrane component receptor DDR-1 and the molecular markers on epidermal melanocytes, dermal stem cells (DSCs), and hair follicle stem cells.

RESULTS: Junctional nevi and compound nevi were prone to occur on glabrous skin, such as the palms, soles, and vulva, and on the extremities in children, whereas intradermal nevi tended to develop on the trunk, head, and face of adults. The immunohistochemical data revealed that both junctional nevi and intradermal nevi expressed the epidermal melanocyte surface markers E-cadherin, DDR-1, and integrin α6 and the DSC molecular markers NGFRp-75 and nestin. CD34 was expressed only in junctional nevi, whereas K19 was not expressed in any type of melanocytic nevi. There was no significant difference in molecular expression at different sites or in different ages of onset. Nestin expression was markedly stronger in the intradermal nevi than in the junctional nevi, but there was no difference between the superficial and deep nevus cell nests of intradermal nevi.

CONCLUSION: AMN may have a multicellular origin that commonly follows the mode of Abtropfung. Furthermore, DSCs may partly or independently participate in the formation of nevus cells.}, } @article {pmid31879283, year = {2020}, author = {Erives, A and Fritzsch, B}, title = {A Screen for Gene Paralogies Delineating Evolutionary Branching Order of Early Metazoa.}, journal = {G3 (Bethesda, Md.)}, volume = {10}, number = {2}, pages = {811-826}, pmid = {31879283}, issn = {2160-1836}, support = {R01 AG060504/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Duplication/radiation effects ; *Genes ; *Genetic Testing/methods ; *Genomics/methods ; Genotype ; Phylogeny ; Plant Proteins ; }, abstract = {The evolutionary diversification of animals is one of Earth's greatest marvels, yet its earliest steps are shrouded in mystery. Animals, the monophyletic clade known as Metazoa, evolved wildly divergent multicellular life strategies featuring ciliated sensory epithelia. In many lineages epithelial sensoria became coupled to increasingly complex nervous systems. Currently, different phylogenetic analyses of single-copy genes support mutually-exclusive possibilities that either Porifera or Ctenophora is sister to all other animals. Resolving this dilemma would advance the ecological and evolutionary understanding of the first animals and the evolution of nervous systems. Here we describe a comparative phylogenetic approach based on gene duplications. We computationally identify and analyze gene families with early metazoan duplications using an approach that mitigates apparent gene loss resulting from the miscalling of paralogs. In the transmembrane channel-like (TMC) family of mechano-transducing channels, we find ancient duplications that define separate clades for Eumetazoa (Placozoa + Cnidaria + Bilateria) vs. Ctenophora, and one duplication that is shared only by Eumetazoa and Porifera. In the Max-like protein X (MLX and MLXIP) family of bHLH-ZIP regulators of metabolism, we find that all major lineages from Eumetazoa and Porifera (sponges) share a duplicated gene pair that is sister to the single-copy gene maintained in Ctenophora. These results suggest a new avenue for deducing deep phylogeny by choosing rather than avoiding ancient gene paralogies.}, } @article {pmid31866780, year = {2019}, author = {Durand, PM and Barreto Filho, MM and Michod, RE}, title = {Cell Death in Evolutionary Transitions in Individuality.}, journal = {The Yale journal of biology and medicine}, volume = {92}, number = {4}, pages = {651-662}, pmid = {31866780}, issn = {1551-4056}, mesh = {Animals ; *Apoptosis ; *Biological Evolution ; Ecological and Environmental Phenomena ; Eukaryotic Cells/cytology/metabolism ; Humans ; Insecta/physiology ; Signal Transduction ; }, abstract = {Programmed cell death (PCD) in cell groups and microbial communities affects population structures, nutrient recycling, and sociobiological interactions. A less explored area is the role played by PCD in the emergence of higher-level individuals. Here, we examine how cell death impacted evolutionary transitions in individuality (ETIs). The focus is on three specific ETIs - the emergence of the eukaryote cell, multicellularity, and social insects - and we review the theoretical and empirical evidence for the role of PCD in these three transitions. We find that PCD likely contributed to many of the processes involved in eukaryogenesis and the transition to multicellularity. PCD is important for the formation of cooperative groups and is a mechanism by which mutual dependencies between individuals evolve. PCD is also a conflict mediator and involved in division of labor in social groups and in the origin of new cell types. In multicellularity, PCD facilitates the transfer of fitness to the higher-level individual. In eusocial insects, PCD of the gonadal cells in workers is the basis for conflict mediation and the division of labor in the colony. In the three ETIs discussed here, PCD likely played an essential role, without which alternate mechanisms would have been necessary for these increases in complexity to occur.}, } @article {pmid31855240, year = {2019}, author = {Pan, H and Dong, Y and Teng, Z and Li, J and Zhang, W and Xiao, T and Wu, LF}, title = {A species of magnetotactic deltaproteobacterium was detected at the highest abundance during an algal bloom.}, journal = {FEMS microbiology letters}, volume = {366}, number = {22}, pages = {}, doi = {10.1093/femsle/fnz253}, pmid = {31855240}, issn = {1574-6968}, mesh = {Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Deltaproteobacteria/*classification/genetics/*isolation & purification/ultrastructure ; *Eutrophication ; Flagella/ultrastructure ; Geologic Sediments/*microbiology ; *Magnetics ; Magnetosomes/ultrastructure ; Microscopy, Electron ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Taxis Response ; }, abstract = {Magnetotactic bacteria (MTB) are a group of microorganisms that have the ability to synthesize intracellular magnetic crystals (magnetosomes). They prefer microaerobic or anaerobic aquatic sediments. Thus, there is growing interest in their ecological roles in various habitats. In this study we found co-occurrence of a large rod-shaped deltaproteobacterial magnetotactic bacterium (tentatively named LR-1) in the sediment of a brackish lagoon with algal bloom. Electron microscopy observations showed that they were ovoid to slightly curved rods having a mean length of 6.3 ± 1.1 μm and a mean width of 4.1 ± 0.4 μm. Each cell had a single polar flagellum. They contained hundreds of bullet-shaped intracellular magnetite magnetosomes. Phylogenetic analysis revealed that they were most closely related to Desulfamplus magnetovallimortis strain BW-1, and belonged to the Deltaproteobacteria. Our findings indicate that LR-1 may be a new species of MTB. We propose that deltaproteobacterial MTB may play an important role in iron cycling and so may represent a reservoir of iron, and be an indicator species for monitoring algal blooms in such eutrophic ecosystems. These observations provide new clues to the cultivation of magnetotactic Deltaproteobacteria and the control of algal blooms, although further studies are needed.}, } @article {pmid31854473, year = {2020}, author = {Costa, ML and de Andrade Rosa, I and Andrade, L and Mermelstein, C and C Coutinho, C}, title = {Distinct interactions between epithelial and mesenchymal cells control cell morphology and collective migration during sponge epithelial to mesenchymal transition.}, journal = {Journal of morphology}, volume = {281}, number = {2}, pages = {183-195}, doi = {10.1002/jmor.21090}, pmid = {31854473}, issn = {1097-4687}, mesh = {Animals ; Cell Aggregation ; *Cell Movement ; *Cell Shape ; Epithelial Cells/*cytology/ultrastructure ; *Epithelial-Mesenchymal Transition ; Mesoderm/*cytology/ultrastructure ; Porifera/*cytology/ultrastructure ; }, abstract = {Epithelial and mesenchymal cell types are basic for animal multicellularity and they have complementary functions coordinated by cellular interactions. Sponges are especially important model organisms to address the evolutionary basis of morphogenetic programs for epithelial and mesenchymal organization in animals. Evolutionary studies in sponges can contribute to the understanding of the mechanisms that control tissue maintenance and tumor progression in humans. In the present study, sponge mesenchymal and epithelial cells were isolated from the demosponge Hymeniacidon heliophila, and aggregate formation was observed by video microscopy. Epithelial-mesenchymal interaction, epithelial transition, and cell migration led to sponge cell aggregation after drastic stress. Based on their different morphologies, adhesion specificities, and motilities, we suggest a role for different sponge cell types as well as complementary functions in cell aggregation. Micromanipulation under the microscope and cell tracking were also used to promote specific grafting-host interaction, to further test the effects of cell type interaction. The loss of cell polarity and flattened shape during the epithelial to mesenchymal cell transition generated small immobile aggregates of round/amoeboid cells. The motility of these transited epithelial-cell aggregates was observed by cell tracking using fluorescent dye, but only after interaction with streams of migratory mesenchymal cells. Cell motility occurred independently of morphological changes, indicating a progressive step in the transition toward a migratory mesenchymal state. Our data suggest a two-step signaling process: (a) the lack of interaction between mesenchymal and epithelial cells triggers morphological changes; and (b) migratory mesenchymal cells instruct epithelial cells for directional cell motility. These results could have an impact on the understanding of evolutionary aspects of metastatic cancer cells. HIGHLIGHTS: Morphogenetic movements observed in modern sponges could have a common evolutionary origin with collective cell migration of human metastatic cells. A sponge regenerative model was used here to characterize epithelial and mesenchymal cells, and for the promotion of grafting/host interactions with subsequent cell tracking. The transition from epithelial to mesenchymal cell type can be observed in sponges in two steps: (a) withdrawal of epithelial/mesenchymal cell interactions to trigger morphological changes; (b) migratory mesenchymal cells to induce epithelial cells to a collective migratory state.}, } @article {pmid31847093, year = {2019}, author = {Nakamura, T and Fahmi, M and Tanaka, J and Seki, K and Kubota, Y and Ito, M}, title = {Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.}, journal = {International journal of molecular sciences}, volume = {20}, number = {24}, pages = {}, pmid = {31847093}, issn = {1422-0067}, support = {NA//MEXT-Supported Program for the Strategic Research Foundation at Private Universities (2015-2019)/ ; NA//Takeda Science Foundation/ ; }, mesh = {*Computer Simulation ; *Databases, Genetic ; Genome-Wide Association Study ; Glycoside Hydrolases/classification/*genetics ; Humans ; }, abstract = {Glycans are involved in various metabolic processes via the functions of glycosyltransferases and glycoside hydrolases. Analysing the evolution of these enzymes is essential for improving the understanding of glycan metabolism and function. Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases. Using cluster analysis, 319 human glycoside hydrolases were classified into four clusters based on their similarity to enzymes conserved in chordates or metazoans (Class 1), metazoans (Class 2), metazoans and plants (Class 3) and eukaryotes (Class 4). The eukaryote and metazoan clusters included N- and O-glycoside hydrolases, respectively. The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases. These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.}, } @article {pmid31845961, year = {2020}, author = {Majic, P and Payne, JL}, title = {Enhancers Facilitate the Birth of De Novo Genes and Gene Integration into Regulatory Networks.}, journal = {Molecular biology and evolution}, volume = {37}, number = {4}, pages = {1165-1178}, pmid = {31845961}, issn = {1537-1719}, mesh = {Animals ; DNA, Intergenic ; *Enhancer Elements, Genetic ; *Evolution, Molecular ; *Gene Regulatory Networks ; Mice ; Open Reading Frames ; Promoter Regions, Genetic ; Transcription, Genetic ; }, abstract = {Regulatory networks control the spatiotemporal gene expression patterns that give rise to and define the individual cell types of multicellular organisms. In eumetazoa, distal regulatory elements called enhancers play a key role in determining the structure of such networks, particularly the wiring diagram of "who regulates whom." Mutations that affect enhancer activity can therefore rewire regulatory networks, potentially causing adaptive changes in gene expression. Here, we use whole-tissue and single-cell transcriptomic and chromatin accessibility data from mouse to show that enhancers play an additional role in the evolution of regulatory networks: They facilitate network growth by creating transcriptionally active regions of open chromatin that are conducive to de novo gene evolution. Specifically, our comparative transcriptomic analysis with three other mammalian species shows that young, mouse-specific intergenic open reading frames are preferentially located near enhancers, whereas older open reading frames are not. Mouse-specific intergenic open reading frames that are proximal to enhancers are more highly and stably transcribed than those that are not proximal to enhancers or promoters, and they are transcribed in a limited diversity of cellular contexts. Furthermore, we report several instances of mouse-specific intergenic open reading frames proximal to promoters showing evidence of being repurposed enhancers. We also show that open reading frames gradually acquire interactions with enhancers over macroevolutionary timescales, helping integrate genes-those that have arisen de novo or by other means-into existing regulatory networks. Taken together, our results highlight a dual role of enhancers in expanding and rewiring gene regulatory networks.}, } @article {pmid31841515, year = {2019}, author = {Lamelza, P and Young, JM and Noble, LM and Caro, L and Isakharov, A and Palanisamy, M and Rockman, MV and Malik, HS and Ailion, M}, title = {Hybridization promotes asexual reproduction in Caenorhabditis nematodes.}, journal = {PLoS genetics}, volume = {15}, number = {12}, pages = {e1008520}, pmid = {31841515}, issn = {1553-7404}, support = {R01 GM074108/GM/NIGMS NIH HHS/United States ; R01 GM121828/GM/NIGMS NIH HHS/United States ; T32 GM007270/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis/genetics/*physiology ; Female ; Fertility ; *Hybridization, Genetic ; Male ; Maternal Inheritance ; Parthenogenesis ; Paternal Inheritance ; *Reproduction, Asexual ; Whole Genome Sequencing ; }, abstract = {Although most unicellular organisms reproduce asexually, most multicellular eukaryotes are obligately sexual. This implies that there are strong barriers that prevent the origin or maintenance of asexuality arising from an obligately sexual ancestor. By studying rare asexual animal species we can gain a better understanding of the circumstances that facilitate their evolution from a sexual ancestor. Of the known asexual animal species, many originated by hybridization between two ancestral sexual species. The balance hypothesis predicts that genetic incompatibilities between the divergent genomes in hybrids can modify meiosis and facilitate asexual reproduction, but there are few instances where this has been shown. Here we report that hybridizing two sexual Caenorhabditis nematode species (C. nouraguensis females and C. becei males) alters the normal inheritance of the maternal and paternal genomes during the formation of hybrid zygotes. Most offspring of this interspecies cross die during embryogenesis, exhibiting inheritance of a diploid C. nouraguensis maternal genome and incomplete inheritance of C. becei paternal DNA. However, a small fraction of offspring develop into viable adults that can be either fertile or sterile. Fertile offspring are produced asexually by sperm-dependent parthenogenesis (also called gynogenesis or pseudogamy); these progeny inherit a diploid maternal genome but fail to inherit a paternal genome. Sterile offspring are hybrids that inherit both a diploid maternal genome and a haploid paternal genome. Whole-genome sequencing of individual viable worms shows that diploid maternal inheritance in both fertile and sterile offspring results from an altered meiosis in C. nouraguensis oocytes and the inheritance of two randomly selected homologous chromatids. We hypothesize that hybrid incompatibility between C. nouraguensis and C. becei modifies maternal and paternal genome inheritance and indirectly induces gynogenetic reproduction. This system can be used to dissect the molecular mechanisms by which hybrid incompatibilities can facilitate the emergence of asexual reproduction.}, } @article {pmid31841362, year = {2020}, author = {Damer, B and Deamer, D}, title = {The Hot Spring Hypothesis for an Origin of Life.}, journal = {Astrobiology}, volume = {20}, number = {4}, pages = {429-452}, pmid = {31841362}, issn = {1557-8070}, mesh = {Artificial Cells ; Biological Evolution ; Desiccation ; Earth, Planet ; Evolution, Chemical ; *Hot Springs ; Hydrogels ; Lipids ; *Models, Theoretical ; *Origin of Life ; Polymers/*chemistry ; Water/*chemistry ; }, abstract = {We present a testable hypothesis related to an origin of life on land in which fluctuating volcanic hot spring pools play a central role. The hypothesis is based on experimental evidence that lipid-encapsulated polymers can be synthesized by cycles of hydration and dehydration to form protocells. Drawing on metaphors from the bootstrapping of a simple computer operating system, we show how protocells cycling through wet, dry, and moist phases will subject polymers to combinatorial selection and draw structural and catalytic functions out of initially random sequences, including structural stabilization, pore formation, and primitive metabolic activity. We propose that protocells aggregating into a hydrogel in the intermediate moist phase of wet-dry cycles represent a primitive progenote system. Progenote populations can undergo selection and distribution, construct niches in new environments, and enable a sharing network effect that can collectively evolve them into the first microbial communities. Laboratory and field experiments testing the first steps of the scenario are summarized. The scenario is then placed in a geological setting on the early Earth to suggest a plausible pathway from life's origin in chemically optimal freshwater hot spring pools to the emergence of microbial communities tolerant to more extreme conditions in dilute lakes and salty conditions in marine environments. A continuity is observed for biogenesis beginning with simple protocell aggregates, through the transitional form of the progenote, to robust microbial mats that leave the fossil imprints of stromatolites so representative in the rock record. A roadmap to future testing of the hypothesis is presented. We compare the oceanic vent with land-based pool scenarios for an origin of life and explore their implications for subsequent evolution to multicellular life such as plants. We conclude by utilizing the hypothesis to posit where life might also have emerged in habitats such as Mars or Saturn's icy moon Enceladus. "To postulate one fortuitously catalyzed reaction, perhaps catalyzed by a metal ion, might be reasonable, but to postulate a suite of them is to appeal to magic." -Leslie Orgel.}, } @article {pmid31841132, year = {2020}, author = {Karimi, E and Geslain, E and KleinJan, H and Tanguy, G and Legeay, E and Corre, E and Dittami, SM}, title = {Genome Sequences of 72 Bacterial Strains Isolated from Ectocarpus subulatus: A Resource for Algal Microbiology.}, journal = {Genome biology and evolution}, volume = {12}, number = {1}, pages = {3647-3655}, pmid = {31841132}, issn = {1759-6653}, mesh = {Bacteria/genetics/isolation & purification/metabolism ; *Genome, Bacterial ; Phaeophyta/*microbiology ; Phylogeny ; Secondary Metabolism/genetics ; Symbiosis ; Vitamins/biosynthesis ; }, abstract = {Brown algae are important primary producers and ecosystem engineers in the ocean, and Ectocarpus has been established as a laboratory model for this lineage. Like most multicellular organisms, Ectocarpus is associated with a community of microorganisms, a partnership frequently referred to as holobiont due to the tight interconnections between the components. Although genomic resources for the algal host are well established, its associated microbiome is poorly characterized from a genomic point of view, limiting the possibilities of using these types of data to study host-microbe interactions. To address this gap in knowledge, we present the annotated draft genome sequences of seventy-two cultivable Ectocarpus-associated bacteria. A screening of gene clusters related to the production of secondary metabolites revealed terpene, bacteriocin, NRPS, PKS-t3, siderophore, PKS-t1, and homoserine lactone clusters to be abundant among the sequenced genomes. These compounds may be used by the bacteria to communicate with the host and other microbes. Moreover, detoxification and provision of vitamin B pathways have been observed in most sequenced genomes, highlighting potential contributions of the bacterial metabolism toward host fitness and survival. The genomes sequenced in this study form a valuable resource for comparative genomic analyses and evolutionary surveys of alga-associated bacteria. They help establish Ectocarpus as a model for brown algal holobionts and will enable the research community to produce testable hypotheses about the molecular interactions within this complex system.}, } @article {pmid31840777, year = {2019}, author = {Kundert, P and Shaulsky, G}, title = {Cellular allorecognition and its roles in Dictyostelium development and social evolution.}, journal = {The International journal of developmental biology}, volume = {63}, number = {8-9-10}, pages = {383-393}, pmid = {31840777}, issn = {1696-3547}, support = {R35 GM118016/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Cell Adhesion ; Chemotaxis ; Dictyostelium/genetics/*immunology/*physiology ; Glycoproteins/genetics ; Glycosylation ; Ligands ; Models, Biological ; Phenotype ; Protozoan Proteins/genetics ; }, abstract = {The social amoeba Dictyostelium discoideum is a tractable model organism to study cellular allorecognition, which is the ability of a cell to distinguish itself and its genetically similar relatives from more distantly related organisms. Cellular allorecognition is ubiquitous across the tree of life and affects many biological processes. Depending on the biological context, these versatile systems operate both within and between individual organisms, and both promote and constrain functional heterogeneity. Some of the most notable allorecognition systems mediate neural self-avoidance in flies and adaptive immunity in vertebrates. D. discoideum's allorecognition system shares several structures and functions with other allorecognition systems. Structurally, its key regulators reside at a single genomic locus that encodes two highly polymorphic proteins, a transmembrane ligand called TgrC1 and its receptor TgrB1. These proteins exhibit isoform-specific, heterophilic binding across cells. Functionally, this interaction determines the extent to which co-developing D. discoideum strains co-aggregate or segregate during the aggregation phase of multicellular development. The allorecognition system thus affects both development and social evolution, as available evidence suggests that the threat of developmental cheating represents a primary selective force acting on it. Other significant characteristics that may inform the study of allorecognition in general include that D. discoideum's allorecognition system is a continuous and inclusive trait, it is pleiotropic, and it is temporally regulated.}, } @article {pmid31840776, year = {2019}, author = {Medina, JM and Shreenidhi, PM and Larsen, TJ and Queller, DC and Strassmann, JE}, title = {Cooperation and conflict in the social amoeba Dictyostelium discoideum.}, journal = {The International journal of developmental biology}, volume = {63}, number = {8-9-10}, pages = {371-382}, doi = {10.1387/ijdb.190158jm}, pmid = {31840776}, issn = {1696-3547}, mesh = {Altruism ; Biological Evolution ; Dictyostelium/genetics/*physiology ; Genetic Variation ; Genetics, Population ; Genotype ; Models, Biological ; Reproduction ; Selection, Genetic ; Spores, Protozoan/*physiology ; }, abstract = {The social amoeba Dictyostelium discoideum has provided considerable insight into the evolution of cooperation and conflict. Under starvation, D. discoideum amoebas cooperate to form a fruiting body comprised of hardy spores atop a stalk. The stalk development is altruistic because stalk cells die to aid spore dispersal. The high relatedness of cells in fruiting bodies in nature implies that this altruism often benefits relatives. However, since the fruiting body forms through aggregation there is potential for non-relatives to join the aggregate and create conflict over spore and stalk fates. Cheating is common in chimeras of social amoebas, where one genotype often takes advantage of the other and makes more spores. This social conflict is a significant force in nature as indicated by rapid rates of adaptive evolution in genes involved in cheating and its resistance. However, cheating can be prevented by high relatedness, allorecognition via tgr genes, pleiotropy and evolved resistance. Future avenues for the study of cooperation and conflict in D. discoideum include the sexual cycle as well as the relationship between D. discoideum and its bacterial symbionts. D. discoideum's tractability in the laboratory as well as its uncommon mode of aggregative multicellularity have established it as a promising model for future studies of cooperation and conflict.}, } @article {pmid31840775, year = {2019}, author = {Kawabe, Y and Du, Q and Schilde, C and Schaap, P}, title = {Evolution of multicellularity in Dictyostelia.}, journal = {The International journal of developmental biology}, volume = {63}, number = {8-9-10}, pages = {359-369}, pmid = {31840775}, issn = {1696-3547}, mesh = {*Biological Evolution ; Cell Differentiation ; Cyclic AMP/metabolism ; Dictyostelium/*genetics/*physiology ; Gene Expression Regulation ; Genome ; Genomics ; Phenotype ; Phylogeny ; Protein Domains ; Signal Transduction ; }, abstract = {The well-orchestrated multicellular life cycle of Dictyostelium discoideum has fascinated biologists for over a century. Self-organisation of its amoebas into aggregates, migrating slugs and fruiting structures by pulsatile cAMP signalling and their ability to follow separate differentiation pathways in well-regulated proportions continue to be topics under investigation. A striking aspect of D. discoideum development is the recurrent use of cAMP as chemoattractant, differentiation inducing signal and second messenger for other signals that control the developmental programme. D. discoideum is one of >150 species of Dictyostelia and aggregative life styles similar to those of Dictyostelia evolved many times in eukaryotes. Here we review experimental studies investigating how phenotypic complexity and cAMP signalling co-evolved in Dictyostelia. In addition, we summarize comparative genomic studies of multicellular Dictyostelia and unicellular Amoebozoa aimed to identify evolutionary conservation and change in all genes known to be essential for D. discoideum development.}, } @article {pmid31840773, year = {2019}, author = {Nanjundiah, V}, title = {Individual and collective behaviour in cellular slime mould development: contributions of John Bonner (1920-2019).}, journal = {The International journal of developmental biology}, volume = {63}, number = {8-9-10}, pages = {333-342}, doi = {10.1387/ijdb.190272vn}, pmid = {31840773}, issn = {1696-3547}, mesh = {Animals ; Biological Evolution ; Body Patterning ; Cell Biology/history ; Chemotaxis ; Developmental Biology/history ; Dictyostelium/*genetics/*physiology ; History, 20th Century ; History, 21st Century ; Humans ; Models, Biological ; Selection, Genetic ; }, abstract = {John Bonner used the cellular slime moulds to address issues that lie at the heart of evolutionary and developmental biology. He did so mostly by combining acute observation and a knack for asking the right questions with the methods of classical embryology. The present paper focusses on his contributions to understanding two phenomena that are characteristic of development in general: chemotaxis of single cells to an external attractant, and spatial patterning and proportioning of cell types in the multicellular aggregate. Brief mention is also made of other areas of slime mould biology where he made significant inputs. He saw cellular slime moulds as exemplars of development and worthy of study in their own right. His ideas continue to inspire researchers.}, } @article {pmid31830880, year = {2020}, author = {Heredia-Soto, V and Redondo, A and Kreilinger, JJP and Martínez-Marín, V and Berjón, A and Mendiola, M}, title = {3D Culture Modelling: An Emerging Approach for Translational Cancer Research in Sarcomas.}, journal = {Current medicinal chemistry}, volume = {27}, number = {29}, pages = {4778-4788}, doi = {10.2174/0929867326666191212162102}, pmid = {31830880}, issn = {1875-533X}, mesh = {Humans ; *Neoplasm Recurrence, Local ; *Sarcoma/therapy ; Spheroids, Cellular ; *Translational Research, Biomedical ; }, abstract = {Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.}, } @article {pmid31829529, year = {2020}, author = {Rivera-Yoshida, N and Hernández-Terán, A and Escalante, AE and Benítez, M}, title = {Laboratory biases hinder Eco-Evo-Devo integration: Hints from the microbial world.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {334}, number = {1}, pages = {14-24}, doi = {10.1002/jez.b.22917}, pmid = {31829529}, issn = {1552-5015}, mesh = {Bias ; *Biological Evolution ; *Ecosystem ; *Models, Biological ; Myxococcus xanthus/*genetics/*growth & development ; Research Design ; }, abstract = {How specific environmental contexts contribute to the robustness and variation of developmental trajectories and evolutionary transitions is a central point in Ecological Evolutionary Developmental Biology ("Eco-Evo-Devo"). However, the articulation of ecological, evolutionary and developmental processes into integrative frameworks has been elusive, partly because standard experimental designs neglect or oversimplify ecologically meaningful contexts. Microbial models are useful to expose and discuss two possible sources of bias associated with conventional gene-centered experimental designs: the use of laboratory strains and standard laboratory environmental conditions. We illustrate our point by showing how contrasting developmental phenotypes in Myxococcus xanthus depend on the joint variation of temperature and substrate stiffness. Microorganismal development can provide key information for better understanding the role of environmental conditions in the evolution of developmental variation, and to overcome some of the limitations associated with current experimental approaches.}, } @article {pmid31820036, year = {2020}, author = {Arasu, UT and Deen, AJ and Pasonen-Seppänen, S and Heikkinen, S and Lalowski, M and Kärnä, R and Härkönen, K and Mäkinen, P and Lázaro-Ibáñez, E and Siljander, PR and Oikari, S and Levonen, AL and Rilla, K}, title = {HAS3-induced extracellular vesicles from melanoma cells stimulate IHH mediated c-Myc upregulation via the hedgehog signaling pathway in target cells.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {77}, number = {20}, pages = {4093-4115}, pmid = {31820036}, issn = {1420-9071}, support = {276426, 284520//Academy of Finland/ ; 312519//Academy of Finland/ ; }, mesh = {Cell Line ; Cell Line, Tumor ; Cell Proliferation/genetics ; Epithelial-Mesenchymal Transition/genetics ; Extracellular Vesicles/*genetics ; Hedgehog Proteins/*genetics ; Humans ; Hyaluronan Receptors/genetics ; Hyaluronan Synthases/*genetics ; Melanoma/*genetics ; Proto-Oncogene Proteins c-myc/*genetics ; Signal Transduction/genetics ; Up-Regulation/*genetics ; }, abstract = {Intercellular communication is fundamental to the survival and maintenance of all multicellular systems, whereas dysregulation of communication pathways can drive cancer progression. Extracellular vesicles (EVs) are mediators of cell-to-cell communication that regulate a variety of cellular processes involved in tumor progression. Overexpression of a specific plasma membrane enzyme, hyaluronan synthase 3 (HAS3), is one of the factors that can induce EV shedding. HAS3, and particularly its product hyaluronan (HA), are carried by EVs and are known to be associated with the tumorigenic properties of cancer cells. To elucidate the specific effects of cancerous, HAS3-induced EVs on target cells, normal human keratinocytes and melanoma cells were treated with EVs derived from GFP-HAS3 expressing metastatic melanoma cells. We found that the HA receptor CD44 participated in the regulation of EV binding to target cells. Furthermore, GFP-HAS3-positive EVs induced HA secretion, proliferation and invasion of target cells. Our results suggest that HAS3-EVs contains increased quantities of IHH, which activates the target cell hedgehog signaling cascade and leads to the activation of c-Myc and regulation of claspin expression. This signaling of IHH in HAS3-EVs resulted in increased cell proliferation. Claspin immunostaining correlated with HA content in human cutaneous melanocytic lesions, supporting our in vitro findings and suggesting a reciprocal regulation between claspin expression and HA synthesis. This study shows for the first time that EVs originating from HAS3 overexpressing cells carry mitogenic signals that induce proliferation and epithelial-to-mesenchymal transition in target cells. The study also identifies a novel feedback regulation between the hedgehog signaling pathway and HA metabolism in melanoma, mediated by EVs carrying HA and IHH.}, } @article {pmid31819969, year = {2020}, author = {Niklas, KJ and Newman, SA}, title = {The many roads to and from multicellularity.}, journal = {Journal of experimental botany}, volume = {71}, number = {11}, pages = {3247-3253}, pmid = {31819969}, issn = {1460-2431}, mesh = {Animals ; *Biological Evolution ; *Ecosystem ; Fungi/genetics ; Genome ; Plants ; }, abstract = {The multiple origins of multicellularity had far-reaching consequences ranging from the appearance of phenotypically complex life-forms to their effects on Earth's aquatic and terrestrial ecosystems. Yet, many important questions remain. For example, do all lineages and clades share an ancestral developmental predisposition for multicellularity emerging from genomic and biophysical motifs shared from a last common ancestor, or are the multiple origins of multicellularity truly independent evolutionary events? In this review, we highlight recent developments and pitfalls in understanding the evolution of multicellularity with an emphasis on plants (here defined broadly to include the polyphyletic algae), but also draw upon insights from animals and their holozoan relatives, fungi and amoebozoans. Based on our review, we conclude that the evolution of multicellular organisms requires three phases (origination by disparate cell-cell attachment modalities, followed by integration by lineage-specific physiological mechanisms, and autonomization by natural selection) that have been achieved differently in different lineages.}, } @article {pmid31818855, year = {2020}, author = {Hofmann, K}, title = {The Evolutionary Origins of Programmed Cell Death Signaling.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {12}, number = {9}, pages = {}, pmid = {31818855}, issn = {1943-0264}, mesh = {Animals ; *Apoptosis ; Apoptosis Regulatory Proteins/*metabolism ; *Biological Evolution ; Humans ; *Signal Transduction ; }, abstract = {Programmed cell death (PCD) pathways are found in many phyla, ranging from developmentally programmed apoptosis in animals to cell-autonomous programmed necrosis pathways that limit the spread of biotrophic pathogens in multicellular assemblies. Prominent examples for the latter include animal necroptosis and pyroptosis, plant hypersensitive response (HR), and fungal heterokaryon incompatibility (HI) pathways. PCD pathways in the different kingdoms show fundamental differences in execution mechanism, morphology of the dying cells, and in the biological sequelae. Nevertheless, recent studies have revealed remarkable evolutionary parallels, including a striking sequence relationship between the "HeLo" domains found in the pore-forming components of necroptosis and some types of plant HR and fungal HI pathways. Other PCD execution components show cross-kingdom conservation as well, or are derived from prokaryotic ancestors. The currently available data suggest a model, wherein the primordial eukaryotic PCD pathway used proteins similar to present-day plant R-proteins and caused necrotic cell death by direct action of Toll and IL-1 receptor (TIR) and HeLo-like domains.}, } @article {pmid31818848, year = {2020}, author = {Lee, MF and Trotman, LC}, title = {PTEN: Bridging Endocytosis and Signaling.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {10}, number = {10}, pages = {}, pmid = {31818848}, issn = {2157-1422}, support = {P30 CA045508/CA/NCI NIH HHS/United States ; R01 CA137050/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Endocytosis ; Humans ; PTEN Phosphohydrolase/*metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Proto-Oncogene Proteins c-akt/*metabolism ; *Signal Transduction ; }, abstract = {The transduction of signals in the PTEN/PI3-kinase (PI3K) pathway is built around a phosphoinositide (PIP) lipid messenger, phosphatidylinositol trisphosphate, PI(3,4,5)P3 or PIP3 Another, more ancient role of this family of messengers is the control of endocytosis, where a handful of separate PIPs act like postal codes. Prominent among them is PI(3)P, which helps to ensure that endocytic vesicles, their cargo, and membranes themselves reach their correct destinations. Traditionally, the cancer and the endocytic functions of the PI3K signaling pathway have been studied by cancer and membrane biologists, respectively, with some notable but overall minimal overlap. Modern microscopy has enabled monitoring of the PTEN/PI3K pathway in action. Here, we explore the flurry of groundbreaking concepts emerging from those efforts. The discovery that PTEN contains an autonomous PI(3)P reader domain, fused to the catalytic PIP3 eraser domain has prompted us to explore the relationship between PI3K signaling and endocytosis. This revealed how PTEN can achieve signal termination in a precisely controlled fashion, because endocytosis can package the PIP3 signal into discrete units that PTEN will erase. We explore how PTEN can bridge the worlds of endocytosis and PI3K signaling and discuss progress on how PI3K/AKT signaling can be acting from internal membranes. We discuss how the PTEN/PI3K system for growth control may have emerged from principles of endocytosis, and how this development could have affected the evolution of multicellular organisms.}, } @article {pmid31818732, year = {2020}, author = {Shuryak, I}, title = {Review of resistance to chronic ionizing radiation exposure under environmental conditions in multicellular organisms.}, journal = {Journal of environmental radioactivity}, volume = {212}, number = {}, pages = {106128}, doi = {10.1016/j.jenvrad.2019.106128}, pmid = {31818732}, issn = {1879-1700}, mesh = {Animals ; Humans ; Phylogeny ; *Radiation Exposure ; *Radiation Monitoring ; Radiation, Ionizing ; Radioisotopes ; }, abstract = {Ionizing radiation resistance occurs among many phylogenetic groups and its mechanisms remain incompletely understood. Tolerances to acute and chronic irradiation do not always correlate because different mechanisms may be involved. The radioresistance phenomenon becomes even more complex in the field than in the laboratory because the effects of radioactive contamination on natural populations are intertwined with those of other factors, such as bioaccumulation of radionuclides, interspecific competition, seasonal variations in environmental conditions, and land use changes due to evacuation of humans from contaminated areas. Previous reviews of studies performed in radioactive sites like the Kyshtym, Chernobyl, and Fukushima accident regions, and of protracted irradiation experiments, often focused on detecting radiation effects at low doses in radiosensitive organisms. Here we review the literature with a different purpose: to identify organisms with high tolerance to chronic irradiation under environmental conditions, which maintained abundant populations and/or outcompeted more radiosensitive species at high dose rates. Taxa for which consistent evidence for radioresistance came from multiple studies conducted in different locations and at different times were found among plants (e.g. willow and birch trees, sedges), invertebrate and vertebrate animals (e.g. rotifers, some insects, crustaceans and freshwater fish). These organisms are not specialized "extremophiles", but tend to tolerate broad ranges of environmental conditions and stresses, have small genomes, reproduce quickly and/or disperse effectively over long distances. Based on these findings, resistance to radioactive contamination can be examined in a more broad context of chronic stress responses.}, } @article {pmid31814500, year = {2020}, author = {Nguyen, H and Das, U and Xie, J}, title = {Genome-wide evolution of wobble base-pairing nucleotides of branchpoint motifs with increasing organismal complexity.}, journal = {RNA biology}, volume = {17}, number = {3}, pages = {311-324}, pmid = {31814500}, issn = {1555-8584}, mesh = {Alternative Splicing ; Ascomycota/cytology/*genetics ; *Base Pairing ; Basidiomycota/genetics ; Cytidine/genetics ; Evolution, Molecular ; Fungal Proteins/genetics ; *Genome, Fungal ; *Nucleotide Motifs ; *RNA Splice Sites ; RNA, Small Nuclear ; }, abstract = {How have the branchpoint motifs evolved in organisms of different complexity? Here we identified and examined the consensus motifs (R1C2T3R4A5Y6, R: A or G, Y: C or T) of 898 fungal genomes. In Ascomycota unicellular yeasts, the G4/A4 ratio is mostly (98%) below 0.125 but increases sharply in multicellular species by about 40 times on average, and in the more complex Basidiomycota, it increases further by about 7 times. The global G4 increase is consistent with A4 to G4 transitions in evolution. Of the G4/A4-interacting amino acids of the branchpoint binding protein MSL5 (SF1) and the HSH155 (SF3B1), as well as the 5' splice sites (SS) and U2 snRNA genes, the 5' SS G[3]/A[3] co-vary with the G4 to some extent. However, corresponding increase of the G4-complementary GCAGTA-U2 gene is rare, suggesting wobble-base pairing between the G4-containing branchpoint motif and GTAGTA-U2 in most of these species. Interestingly, the G4/A4 ratio correlates well with the abundance of alternative splicing in the two phyla, and G4 enriched significantly at the alternative 3' SS of genes in RNA metabolism, kinases and membrane proteins. Similar wobble nucleotides also enriched at the 3' SS of multicellular fungi with only thousands of protein-coding genes. Thus, branchpoint motifs have evolved U2-complementarity in unicellular Ascomycota yeasts, but have gradually gained more wobble base-pairing nucleotides in fungi of higher complexity, likely to destabilize branchpoint motif-U2 interaction and/or branchpoint A protrusion for alternative splicing. This implies an important role of relaxing the branchpoint signals in the multicellularity and further complexity of fungi.}, } @article {pmid31805037, year = {2019}, author = {Thomas, F and Giraudeau, M and Renaud, F and Ujvari, B and Roche, B and Pujol, P and Raymond, M and Lemaitre, JF and Alvergne, A}, title = {Can postfertile life stages evolve as an anticancer mechanism?.}, journal = {PLoS biology}, volume = {17}, number = {12}, pages = {e3000565}, pmid = {31805037}, issn = {1545-7885}, mesh = {Adaptation, Physiological/*physiology ; Animals ; Biological Evolution ; Female ; Humans ; Menopause/metabolism/*physiology ; Neoplasms/physiopathology/*prevention & control ; Reproduction/physiology ; }, abstract = {Why a postfertile stage has evolved in females of some species has puzzled evolutionary biologists for over 50 years. We propose that existing adaptive explanations have underestimated in their formulation an important parameter operating both at the specific and the individual levels: the balance between cancer risks and cancer defenses. During their life, most multicellular organisms naturally accumulate oncogenic processes in their body. In parallel, reproduction, notably the pregnancy process in mammals, exacerbates the progression of existing tumors in females. When, for various ecological or evolutionary reasons, anticancer defenses are too weak, given cancer risk, older females could not pursue their reproduction without triggering fatal metastatic cancers, nor even maintain a normal reproductive physiology if the latter also promotes the growth of existing oncogenic processes, e.g., hormone-dependent malignancies. At least until stronger anticancer defenses are selected for in these species, females could achieve higher inclusive fitness by ceasing their reproduction and/or going through menopause (assuming that these traits are easier to select than anticancer defenses), thereby limiting the risk of premature death due to metastatic cancers. Because relatively few species experience such an evolutionary mismatch between anticancer defenses and cancer risks, the evolution of prolonged life after reproduction could also be a rare, potentially transient, anticancer adaptation in the animal kingdom.}, } @article {pmid31802185, year = {2020}, author = {Walker, DM and Hill, AJ and Albecker, MA and McCoy, MW and Grisnik, M and Romer, A and Grajal-Puche, A and Camp, C and Kelehear, C and Wooten, J and Rheubert, J and Graham, SP}, title = {Variation in the Slimy Salamander (Plethodon spp.) Skin and Gut-Microbial Assemblages Is Explained by Geographic Distance and Host Affinity.}, journal = {Microbial ecology}, volume = {79}, number = {4}, pages = {985-997}, doi = {10.1007/s00248-019-01456-x}, pmid = {31802185}, issn = {1432-184X}, mesh = {Animal Distribution ; Animals ; Bacteria/isolation & purification ; *Bacterial Physiological Phenomena ; Fungi/isolation & purification/*physiology ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; *Microbiota ; Mycobiome ; Skin/*microbiology ; Southeastern United States ; Spatial Analysis ; Tennessee ; Urodela/*microbiology ; }, abstract = {A multicellular host and its microbial communities are recognized as a metaorganism-a composite unit of evolution. Microbial communities have a variety of positive and negative effects on the host life history, ecology, and evolution. This study used high-throughput amplicon sequencing to characterize the complete skin and gut microbial communities, including both bacteria and fungi, of a terrestrial salamander, Plethodon glutinosus (Family Plethodontidae). We assessed salamander populations, representing nine mitochondrial haplotypes ('clades'), for differences in microbial assemblages across 13 geographic locations in the Southeastern United States. We hypothesized that microbial assemblages were structured by both host factors and geographic distance. We found a strong correlation between all microbial assemblages at close geographic distances, whereas, as spatial distance increases, the patterns became increasingly discriminate. Network analyses revealed that gut-bacterial communities have the highest degree of connectedness across geographic space. Host salamander clade was explanatory of skin-bacterial and gut-fungal assemblages but not gut-bacterial assemblages, unless the latter were analyzed within a phylogenetic context. We also inferred the function of gut-fungal assemblages to understand how an understudied component of the gut microbiome may influence salamander life history. We concluded that dispersal limitation may in part describe patterns in microbial assemblages across space and also that the salamander host may select for skin and gut communities that are maintained over time in closely related salamander populations.}, } @article {pmid31799909, year = {2020}, author = {Fields, C and Bischof, J and Levin, M}, title = {Morphological Coordination: A Common Ancestral Function Unifying Neural and Non-Neural Signaling.}, journal = {Physiology (Bethesda, Md.)}, volume = {35}, number = {1}, pages = {16-30}, doi = {10.1152/physiol.00027.2019}, pmid = {31799909}, issn = {1548-9221}, mesh = {Animals ; *Biological Evolution ; Humans ; Models, Biological ; Nervous System/*pathology ; Neurons/*physiology ; Regenerative Medicine/methods ; Signal Transduction/*physiology ; }, abstract = {Nervous systems are traditionally thought of as providing sensing and behavioral coordination functions at the level of the whole organism. What is the evolutionary origin of the mechanisms enabling the nervous systems' information processing ability? Here, we review evidence from evolutionary, developmental, and regenerative biology suggesting a deeper, ancestral function of both pre-neural and neural cell-cell communication systems: the long-distance coordination of cell division and differentiation required to create and maintain body-axis symmetries. This conceptualization of the function of nervous system activity sheds new light on the evolutionary transition from the morphologically rudimentary, non-neural Porifera and Placazoa to the complex morphologies of Ctenophores, Cnidarians, and Bilaterians. It further allows a sharp formulation of the distinction between long-distance axis-symmetry coordination based on external coordinates, e.g., by whole-organism scale trophisms as employed by plants and sessile animals, and coordination based on body-centered coordinates as employed by motile animals. Thus we suggest that the systems that control animal behavior evolved from ancient mechanisms adapting preexisting ionic and neurotransmitter mechanisms to regulate individual cell behaviors during morphogenesis. An appreciation of the ancient, non-neural origins of bioelectrically mediated computation suggests new approaches to the study of embryological development, including embryological dysregulation, cancer, regenerative medicine, and synthetic bioengineering.}, } @article {pmid31798628, year = {2019}, author = {Baumgartner, M and Drake, K and Kanadia, RN}, title = {An Integrated Model of Minor Intron Emergence and Conservation.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {1113}, pmid = {31798628}, issn = {1664-8021}, support = {R01 NS102538/NS/NINDS NIH HHS/United States ; }, abstract = {Minor introns constitute <0.5% of the introns in the human genome and have remained an enigma since their discovery. These introns are removed by a distinct splicing complex, the minor spliceosome. Both are ancient, tracing back to the last eukaryotic common ancestor (LECA), which is reflected by minor intron enrichment in specific gene families, such as the mitogen activated-protein kinase kinases, voltage-gated sodium and calcium ion channels, and E2F transcription factors. Most minor introns occur as single introns in genes with predominantly major introns. Due to this organization, minor intron-containing gene (MIG) expression requires the coordinated action of two spliceosomes, which increases the probability of missplicing. Thus, one would expect loss of minor introns via purifying selection. This has resulted in complete minor intron loss in at least nine eukaryotic lineages. However, minor introns are highly conserved in land plants and metazoans, where their importance is underscored by embryonic lethality when the minor spliceosome is inactivated. Conditional inactivation of the minor spliceosome has shown that rapidly dividing progenitor cells are highly sensitive to minor spliceosome loss. Indeed, we found that MIGs were significantly enriched in a screen for genes essential for survival in 341 cycling cell lines. Here, we propose that minor introns inserted randomly into genes in LECA or earlier and were subsequently conserved in genes crucial for cycling cell survival. We hypothesize that the essentiality of MIGs allowed minor introns to endure through the unicellularity of early eukaryotic evolution. Moreover, we identified 59 MIGs that emerged after LECA, and that many of these are essential for cycling cell survival, reinforcing our essentiality model for MIG conservation. This suggests that minor intron emergence is dynamic across eukaryotic evolution, and that minor introns should not be viewed as molecular fossils. We also posit that minor intron splicing was co-opted in multicellular evolution as a regulatory switch for en masse control of MIG expression and the biological processes they regulate. Specifically, this mode of regulation could control cell proliferation and thus body size, an idea supported by domestication syndrome, wherein MIGs are enriched in common candidate animal domestication genes.}, } @article {pmid31798620, year = {2019}, author = {Rockwell, AL and Hongay, CF}, title = {The m[6]A Dynamics of Profilin in Neurogenesis.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {987}, pmid = {31798620}, issn = {1664-8021}, abstract = {Our understanding of the biological role of N [6]-methyladenosine (m[6]A), a ubiquitous non-editing RNA modification, has increased greatly since 2011. More recently, work from several labs revealed that m[6]A methylation regulates several aspects of mRNA metabolism. The "writer" protein METTL3, known as MT-A70 in humans, DmIme4 in flies, and MTA in plants, has the catalytic site of the METTL3/14/16 subunit of the methyltransferase complex that includes many other proteins. METTL3 is evolutionarily conserved and essential for development in multicellular organisms. However, until recently, no study has been able to provide a mechanism that explains the essentiality of METTL3. The addition of m[6]A to gene transcripts has been compared with the epigenetic code of histone modifications because of its effects on gene expression and its reversibility, giving birth to the field of epitranscriptomics, the study of the biological role of this and similar RNA modifications. Here, we focus on METTL3 and its likely conserved role in profilin regulation in neurogenesis. However, this and many other subunits of the methyltransferase complex are starting to be identified in several developmental processes and diseases. A recent plethora of studies about the biological role of METTL3 and other components of the methyltransferase complex that erase (FTO) or recognize (YTH proteins) this modification on transcripts revealed that this RNA modification plays a variety of roles in many biological processes like neurogenesis. Our work in Drosophila shows that the ancient and evolutionarily conserved gene profilin (chic in Drosophila) is a target of the m[6]A writer. Here, we discuss the implications of our study in Drosophila and how it unveils a conserved mechanism in support of the essential function of METTL3 in metazoan development. Profilin (chic) is an essential gene of ancient evolutionary origins, present in sponges (Porifera), the oldest still extant metazoan phylum of the common metazoan ancestor Urmetazoa. We propose that the relationship between profilin and METTL3 is conserved in metazoans and it provides insights into possible regulatory roles of m[6]A modification of profilin transcripts in processes such as neurogenesis.}, } @article {pmid31794757, year = {2019}, author = {Jékely, G}, title = {Evolution: How Not to Become an Animal.}, journal = {Current biology : CB}, volume = {29}, number = {23}, pages = {R1240-R1242}, doi = {10.1016/j.cub.2019.10.014}, pmid = {31794757}, issn = {1879-0445}, mesh = {Animals ; *Choanoflagellata ; }, abstract = {The origin of animals has always fascinated biologists. Studies on choanoflagellates, the closest living relatives of animals, have contributed major insights. The discovery of a multicellular choanoflagellate with light-regulated collective behaviour now provides a new perspective.}, } @article {pmid31792014, year = {2020}, author = {Zuniga, EG and Figueroa, NM and Gonzalez, A and Pantoja, AP and Risser, DD}, title = {The Hybrid Histidine Kinase HrmK Is an Early-Acting Factor in the Hormogonium Gene Regulatory Network.}, journal = {Journal of bacteriology}, volume = {202}, number = {5}, pages = {}, pmid = {31792014}, issn = {1098-5530}, mesh = {Bacterial Proteins/genetics/metabolism ; Evolution, Molecular ; *Gene Expression Regulation, Bacterial ; *Gene Regulatory Networks ; Genetic Loci ; Histidine Kinase/*genetics/metabolism ; Models, Biological ; Nostoc/classification/*genetics/metabolism ; Polysaccharides, Bacterial/metabolism ; }, abstract = {Filamentous, heterocyst-forming cyanobacteria belonging to taxonomic subsections IV and V are developmentally complex multicellular organisms capable of differentiating an array of cell and filament types, including motile hormogonia. Hormogonia exhibit gliding motility that facilitates dispersal, phototaxis, and the establishment of nitrogen-fixing symbioses. The gene regulatory network (GRN) governing hormogonium development involves a hierarchical sigma factor cascade, but the factors governing the activation of this cascade are currently undefined. Here, using a forward genetic approach, we identified hrmK, a gene encoding a putative hybrid histidine kinase that functions upstream of the sigma factor cascade. The deletion of hrmK produced nonmotile filaments that failed to display hormogonium morphology or accumulate hormogonium-specific proteins or polysaccharide. Targeted transcriptional analyses using reverse transcription-quantitative PCR (RT-qPCR) demonstrated that hormogonium-specific genes both within and outside the sigma factor cascade are drastically downregulated in the absence of hrmK and that hrmK may be subject to indirect, positive autoregulation via sigJ and sigC Orthologs of HrmK are ubiquitous among, and exclusive to, heterocyst-forming cyanobacteria. Collectively, these results indicate that hrmK functions upstream of the sigma factor cascade to initiate hormogonium development, likely by modulating the phosphorylation state of an unknown protein that may serve as the master regulator of hormogonium development in heterocyst-forming cyanobacteria.IMPORTANCE Filamentous cyanobacteria are morphologically complex, with several representative species amenable to routine genetic manipulation, making them excellent model organisms for the study of development. Furthermore, two of the developmental alternatives, nitrogen-fixing heterocysts and motile hormogonia, are essential to establish nitrogen-fixing symbioses with plant partners. These symbioses are integral to global nitrogen cycles and could be artificially recreated with crop plants to serve as biofertilizers, but to achieve this goal, detailed understanding and manipulation of the hormogonium and heterocyst gene regulatory networks may be necessary. Here, using the model organism Nostoc punctiforme, we identify a previously uncharacterized hybrid histidine kinase that is confined to heterocyst-forming cyanobacteria as the earliest known participant in hormogonium development.}, } @article {pmid31788034, year = {2019}, author = {Southworth, J and Grace, CA and Marron, AO and Fatima, N and Carr, M}, title = {A genomic survey of transposable elements in the choanoflagellate Salpingoeca rosetta reveals selection on codon usage.}, journal = {Mobile DNA}, volume = {10}, number = {}, pages = {44}, pmid = {31788034}, issn = {1759-8753}, abstract = {BACKGROUND: Unicellular species make up the majority of eukaryotic diversity, however most studies on transposable elements (TEs) have centred on multicellular host species. Such studies may have therefore provided a limited picture of how transposable elements evolve across eukaryotes. The choanoflagellates, as the sister group to Metazoa, are an important study group for investigating unicellular to multicellular transitions. A previous survey of the choanoflagellate Monosiga brevicollis revealed the presence of only three families of LTR retrotransposons, all of which appeared to be active. Salpingoeca rosetta is the second choanoflagellate to have its whole genome sequenced and provides further insight into the evolution and population biology of transposable elements in the closest relative of metazoans.

RESULTS: Screening the genome revealed the presence of a minimum of 20 TE families. Seven of the annotated families are DNA transposons and the remaining 13 families are LTR retrotransposons. Evidence for two putative non-LTR retrotransposons was also uncovered, but full-length sequences could not be determined. Superfamily phylogenetic trees indicate that vertical inheritance and, in the case of one family, horizontal transfer have been involved in the evolution of the choanoflagellates TEs. Phylogenetic analyses of individual families highlight recent element activity in the genome, however six families did not show evidence of current transposition. The majority of families possess young insertions and the expression levels of TE genes vary by four orders of magnitude across families. In contrast to previous studies on TEs, the families present in S. rosetta show the signature of selection on codon usage, with families favouring codons that are adapted to the host translational machinery. Selection is stronger in LTR retrotransposons than DNA transposons, with highly expressed families showing stronger codon usage bias. Mutation pressure towards guanosine and cytosine also appears to contribute to TE codon usage.

CONCLUSIONS: S. rosetta increases the known diversity of choanoflagellate TEs and the complement further highlights the role of horizontal gene transfer from prey species in choanoflagellate genome evolution. Unlike previously studied TEs, the S. rosetta families show evidence for selection on their codon usage, which is shown to act via translational efficiency and translational accuracy.}, } @article {pmid31766724, year = {2019}, author = {Kar, R and Jha, NK and Jha, SK and Sharma, A and Dholpuria, S and Asthana, N and Chaurasiya, K and Singh, VK and Burgee, S and Nand, P}, title = {A "NOTCH" Deeper into the Epithelial-To-Mesenchymal Transition (EMT) Program in Breast Cancer.}, journal = {Genes}, volume = {10}, number = {12}, pages = {}, pmid = {31766724}, issn = {2073-4425}, mesh = {Animals ; Breast Neoplasms/*genetics ; *Epithelial-Mesenchymal Transition ; Female ; Humans ; Receptors, Notch/*genetics ; Signal Transduction ; }, abstract = {Notch signaling is a primitive signaling pathway having various roles in the normal origin and development of each multicellular organisms. Therefore, any aberration in the pathway will inevitably lead to deadly outcomes such as cancer. It has now been more than two decades since Notch was acknowledged as an oncogene in mouse mammary tumor virus-infected mice. Since that discovery, activated Notch signaling and consequent up-regulation of tumor-promoting Notch target genes have been observed in human breast cancer. Moreover, consistent over-expression of Notch ligands and receptors has been shown to correlate with poor prognosis in human breast cancer. Notch regulates a number of key processes during breast carcinogenesis, of which, one key phenomenon is epithelial-mesenchymal transition (EMT). EMT is a key process for large-scale cell movement during morphogenesis at the time of embryonic development. Cancer cells aided by transcription factors usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis. In this review, we recapitulate recent progress in breast cancer research that has provided new perceptions into the molecular mechanisms behind Notch-mediated EMT regulation during breast tumorigenesis.}, } @article {pmid31752673, year = {2019}, author = {Forbes, G and Chen, ZH and Kin, K and Lawal, HM and Schilde, C and Yamada, Y and Schaap, P}, title = {Phylogeny-wide conservation and change in developmental expression, cell-type specificity and functional domains of the transcriptional regulators of social amoebas.}, journal = {BMC genomics}, volume = {20}, number = {1}, pages = {890}, pmid = {31752673}, issn = {1471-2164}, support = {100293/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; 742288//H2020 European Research Council/ ; RPG-2016-220//Leverhulme Trust/ ; ALTF 295-2015//European Molecular Biology Organization/ ; H28-1002//Japan Society for the Promotion of Science/ ; }, mesh = {Amoebozoa/classification/*genetics/growth & development/metabolism ; Dictyostelium/genetics ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Phenotype ; Phylogeny ; Protein Domains ; Transcription Factors/chemistry/*genetics/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: Dictyostelid social amoebas self-organize into fruiting bodies, consisting of spores and up to four supporting cell types in the phenotypically most complex taxon group 4. High quality genomes and stage- and cell-type specific transcriptomes are available for representative species of each of the four taxon groups. To understand how evolution of gene regulation in Dictyostelia contributed to evolution of phenotypic complexity, we analysed conservation and change in abundance, functional domain architecture and developmental regulation of their transcription factors (TFs).

RESULTS: We detected 440 sequence-specific TFs across 33 families, of which 68% were upregulated in multicellular development and about half conserved throughout Dictyostelia. Prespore cells expressed two times more TFs than prestalk cells, but stalk cells expressed more TFs than spores, suggesting that gene expression events that define spores occur earlier than those that define stalk cells. Changes in TF developmental expression, but not in TF abundance or functional domains occurred more frequently between group 4 and groups 1-3, than between the more distant branches formed by groups 1 + 2 and 3 + 4.

CONCLUSIONS: Phenotypic innovation is correlated with changes in TF regulation, rather than functional domain- or TF acquisition. The function of only 34 TFs is known. Of 12 TFs essential for cell differentiation, 9 are expressed in the cell type for which they are required. The information acquired here on conserved cell type specifity of 120 additional TFs can effectively guide further functional analysis, while observed evolutionary change in TF developmental expression may highlight how genotypic change caused phenotypic innovation.}, } @article {pmid31751628, year = {2020}, author = {Williams, LM and Inge, MM and Mansfield, KM and Rasmussen, A and Afghani, J and Agrba, M and Albert, C and Andersson, C and Babaei, M and Babaei, M and Bagdasaryants, A and Bonilla, A and Browne, A and Carpenter, S and Chen, T and Christie, B and Cyr, A and Dam, K and Dulock, N and Erdene, G and Esau, L and Esonwune, S and Hanchate, A and Huang, X and Jennings, T and Kasabwala, A and Kehoe, L and Kobayashi, R and Lee, M and LeVan, A and Liu, Y and Murphy, E and Nambiar, A and Olive, M and Patel, D and Pavesi, F and Petty, CA and Samofalova, Y and Sanchez, S and Stejskal, C and Tang, Y and Yapo, A and Cleary, JP and Yunes, SA and Siggers, T and Gilmore, TD}, title = {Transcription factor NF-κB in a basal metazoan, the sponge, has conserved and unique sequences, activities, and regulation.}, journal = {Developmental and comparative immunology}, volume = {104}, number = {}, pages = {103559}, doi = {10.1016/j.dci.2019.103559}, pmid = {31751628}, issn = {1879-0089}, support = {R01 AI116829/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Conserved Sequence/*genetics ; DNA-Binding Proteins/*genetics/metabolism ; Evolution, Molecular ; Gene Expression Regulation ; NF-kappa B/*genetics/metabolism ; Porifera/*immunology ; Protein Domains/*genetics ; Signal Transduction ; Transcription, Genetic ; }, abstract = {Herein, we characterize transcription factor NF-κB from the demosponge Amphimedon queenslandica (Aq). Aq-NF-κB is most similar to NF-κB p100/p105 among vertebrate proteins, with an N-terminal DNA-binding domain, a C-terminal Ankyrin (ANK) repeat domain, and a DNA binding-site profile akin to human NF-κB proteins. Like mammalian NF-κB p100, C-terminal truncation allows nuclear translocation of Aq-NF-κB and increases its transcriptional activation activity. Expression of IκB kinases (IKKs) induces proteasome-dependent C-terminal processing of Aq-NF-κB in human cells, and processing requires C-terminal serines in Aq-NF-κB. Unlike NF-κB p100, C-terminal sequences of Aq-NF-κB do not inhibit its DNA-binding activity. Tissue of a black encrusting demosponge contains NF-κB site DNA-binding activity, as well as nuclear and processed NF-κB. Treatment of sponge tissue with LPS increases both DNA-binding activity and processing of NF-κB. A. queenslandica transcriptomes contain homologs to upstream NF-κB pathway components. This is first functional characterization of NF-κB in sponge, the most basal multicellular animal.}, } @article {pmid31744876, year = {2019}, author = {Vassallo, CN and Wall, D}, title = {Self-identity barcodes encoded by six expansive polymorphic toxin families discriminate kin in myxobacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {49}, pages = {24808-24818}, pmid = {31744876}, issn = {1091-6490}, support = {R01 GM101449/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Bacterial Outer Membrane Proteins/genetics/metabolism ; Bacterial Toxins/classification/*genetics/immunology/*isolation & purification ; Cation Transport Proteins/genetics/metabolism ; Lipoproteins ; Myxococcales/*genetics/*metabolism ; Myxococcus xanthus/genetics/metabolism ; Phylogeny ; Receptors, Cell Surface/*metabolism ; Sequence Analysis ; }, abstract = {Myxobacteria are an example of how single-cell individuals can transition into multicellular life by an aggregation strategy. For these and all organisms that consist of social groups of cells, discrimination against, and exclusion of, nonself is critical. In myxobacteria, TraA is a polymorphic cell surface receptor that identifies kin by homotypic binding, and in so doing exchanges outer membrane (OM) proteins and lipids between cells with compatible receptors. However, TraA variability alone is not sufficient to discriminate against all cells, as traA allele diversity is not necessarily high among local strains. To increase discrimination ability, myxobacteria include polymorphic OM lipoprotein toxins called SitA in their delivered cargo, which poison recipient cells that lack the cognate, allele-specific SitI immunity protein. We previously characterized 3 SitAI toxin/immunity pairs that belong to 2 families. Here, we discover 4 additional SitA families. Each family is unique in sequence, but share the characteristic features of SitA: OM-associated toxins delivered by TraA. We demonstrate that, within a SitA family, C-terminal nuclease domains are polymorphic and often modular. Remarkably, sitA loci are strikingly numerous and diverse, with most genomes possessing >30 and up to 83 distinct sitAI loci. Interestingly, all SitA protein families are serially transferred between cells, allowing a SitA inhibitor cell to poison multiple targets, including cells that never made direct contact. The expansive suites of sitAI loci thus serve as identify barcodes to exquisitely discriminate against nonself to ensure populations are genetically homogenous to conduct cooperative behaviors.}, } @article {pmid31743442, year = {2020}, author = {Brenneis, G and Beltz, BS}, title = {Adult neurogenesis in crayfish: Origin, expansion, and migration of neural progenitor lineages in a pseudostratified neuroepithelium.}, journal = {The Journal of comparative neurology}, volume = {528}, number = {9}, pages = {1459-1485}, doi = {10.1002/cne.24820}, pmid = {31743442}, issn = {1096-9861}, mesh = {Animals ; Astacoidea/*cytology/physiology ; Brain/*cytology ; Cell Differentiation/physiology ; Cell Lineage/physiology ; Cell Movement/physiology ; Hemocytes/cytology ; Neural Stem Cells/*cytology ; Neurogenesis/*physiology ; }, abstract = {Two decades after the discovery of adult-born neurons in the brains of decapod crustaceans, the deutocerebral proliferative system (DPS) producing these neural lineages has become a model of adult neurogenesis in invertebrates. Studies on crayfish have provided substantial insights into the anatomy, cellular dynamics, and regulation of the DPS. Contrary to traditional thinking, recent evidence suggests that the neurogenic niche in the crayfish DPS lacks self-renewing stem cells, its cell pool being instead sustained via integration of hemocytes generated by the innate immune system. Here, we investigated the origin, division and migration patterns of the adult-born neural progenitor (NP) lineages in detail. We show that the niche cell pool is not only replenished by hemocyte integration but also by limited numbers of symmetric cell divisions with some characteristics reminiscent of interkinetic nuclear migration. Once specified in the niche, first generation NPs act as transit-amplifying intermediate NPs that eventually exit and produce multicellular clones as they move along migratory streams toward target brain areas. Different clones may migrate simultaneously in the streams but occupy separate tracks and show spatio-temporally flexible division patterns. Based on this, we propose an extended DPS model that emphasizes structural similarities to pseudostratified neuroepithelia in other arthropods and vertebrates. This model includes hemocyte integration and intrinsic cell proliferation to synergistically counteract niche cell pool depletion during the animal's lifespan. Further, we discuss parallels to recent findings on mammalian adult neurogenesis, as both systems seem to exhibit a similar decoupling of proliferative replenishment divisions and consuming neurogenic divisions.}, } @article {pmid31736534, year = {2019}, author = {Chen, J and Wang, N}, title = {Tissue cell differentiation and multicellular evolution via cytoskeletal stiffening in mechanically stressed microenvironments.}, journal = {Acta mechanica Sinica = Li xue xue bao}, volume = {35}, number = {2}, pages = {270-274}, pmid = {31736534}, issn = {0567-7718}, support = {R01 GM072744/GM/NIGMS NIH HHS/United States ; }, abstract = {Evolution of eukaryotes from simple cells to complex multicellular organisms remains a mystery. Our postulate is that cytoskeletal stiffening is a necessary condition for evolution of complex multicellular organisms from early simple eukaryotes. Recent findings show that embryonic stem cells are as soft as primitive eukaryotes-amoebae and that differentiated tissue cells can be two orders of magnitude stiffer than embryonic stem cells. Soft embryonic stem cells become stiff as they differentiate into tissue cells of the complex multicellular organisms to match their microenvironment stiffness. We perhaps see in differentiation of embryonic stem cells (derived from inner cell mass cells) the echo of those early evolutionary events. Early soft unicellular organisms might have evolved to stiffen their cytoskeleton to protect their structural integrity from external mechanical stresses while being able to maintain form, to change shape, and to move.}, } @article {pmid31724951, year = {2019}, author = {Thattai, M}, title = {How contraction has shaped evolution.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {31724951}, issn = {2050-084X}, mesh = {*Actin Cytoskeleton ; *Actomyosin ; Animals ; }, abstract = {Two unicellular relatives of animals reveal that coordinated contractions of groups of cells using actomyosin predated animal multicellularity during evolution.}, } @article {pmid31722397, year = {2020}, author = {López, EH and Palumbi, SR}, title = {Somatic Mutations and Genome Stability Maintenance in Clonal Coral Colonies.}, journal = {Molecular biology and evolution}, volume = {37}, number = {3}, pages = {828-838}, doi = {10.1093/molbev/msz270}, pmid = {31722397}, issn = {1537-1719}, mesh = {Animals ; Anthozoa/*genetics ; Clonal Evolution ; Coral Reefs ; Gene Expression Profiling/*methods ; Genomic Instability ; Loss of Heterozygosity ; *Mutation ; Mutation Rate ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/*methods ; }, abstract = {One challenge for multicellular organisms is maintaining genome stability in the face of mutagens across long life spans. Imperfect genome maintenance leads to mutation accumulation in somatic cells, which is associated with tumors and senescence in vertebrates. Colonial reef-building corals are often large, can live for hundreds of years, rarely develop recognizable tumors, and are thought to convert somatic cells into gamete producers, so they are a pivotal group in which to understand long-term genome maintenance. To measure rates and patterns of somatic mutations, we analyzed transcriptomes from 17 to 22 branches from each of four Acropora hyacinthus colonies, determined putative single nucleotide variants, and verified them with Sanger resequencing. Unlike for human skin carcinomas, there is no signature of mutations caused by UV damage, indicating either higher efficiency of repair than in vertebrates, or strong sunscreen protection in these shallow water tropical animals. The somatic mutation frequency per nucleotide in A. hyacinthus is on the same order of magnitude (10-7) as noncancerous human somatic cells, and accumulation of mutations with age is similar. Loss of heterozygosity variants outnumber gain of heterozygosity mutations ∼2:1. Although the mutation frequency is similar in mammals and corals, the preponderance of loss of heterozygosity changes and potential selection may reduce the frequency of deleterious mutations in colonial animals like corals. This may limit the deleterious effects of somatic mutations on the coral organism as well as potential offspring.}, } @article {pmid31721091, year = {2020}, author = {Martínez-Soto, D and Velez-Haro, JM and León-Ramírez, CG and Galán-Vásquez, E and Chávez-Munguía, B and Ruiz-Herrera, J}, title = {Multicellular growth of the Basidiomycota phytopathogen fungus Sporisorium reilianum induced by acid conditions.}, journal = {Folia microbiologica}, volume = {65}, number = {3}, pages = {511-521}, doi = {10.1007/s12223-019-00755-7}, pmid = {31721091}, issn = {1874-9356}, mesh = {Acids/*pharmacology ; Basidiomycota/drug effects/*genetics/*growth & development ; Cell Cycle/drug effects ; Cell Division/drug effects ; Fungal Proteins/*genetics ; Hydrogen-Ion Concentration ; Phylogeny ; Signal Transduction/drug effects ; }, abstract = {Fungi are considered model organisms for the analysis of important phenomena of eukaryotes. For example, some of them have been described as models to understand the phenomenon of multicellularity acquisition by different unicellular organisms phylogenetically distant. Interestingly, in this work, we describe the multicellular development in the model fungus S. reilianum. We observed that Sporisorium reilianum, a Basidiomycota cereal pathogen that at neutral pH grows with a yeast-like morphology during its saprophytic haploid stage, when incubated at acid pH grew in the form of multicellular clusters. The multicellularity observed in S. reilianum was of clonal type, where buds of "stem" cells growing as yeasts remain joined by their cell wall septa, after cytokinesis. The elaboration and analysis of a regulatory network of S. reilianum showed that the putative zinc finger transcription factor CBQ73544.1 regulates a number of genes involved in cell cycle, cellular division, signal transduction pathways, and biogenesis of cell wall. Interestingly, homologous of these genes have been found to be regulated during Saccharomyces cerevisiae multicellular growth. In adddition, some of these genes were found to be negatively regulated during multicellularity of S. reilianum. With these data, we suggest that S. reilianum is an interesting model for the study of multicellular development.}, } @article {pmid31714927, year = {2019}, author = {Hammond, MJ and Wang, T and Cummins, SF}, title = {Characterisation of early metazoan secretion through associated signal peptidase complex subunits, prohormone convertases and carboxypeptidases of the marine sponge (Amphimedon queenslandica).}, journal = {PloS one}, volume = {14}, number = {11}, pages = {e0225227}, pmid = {31714927}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Carboxypeptidases/chemistry/genetics/*metabolism ; Phylogeny ; Porifera/classification/genetics/*metabolism ; Proprotein Convertases/chemistry/genetics/*metabolism ; Protein Subunits/chemistry/*metabolism ; *Signal Transduction ; }, abstract = {Efficient communication between cells requires the ability to process precursor proteins into their mature and biologically active forms, prior to secretion into the extracellular space. Eukaryotic cells achieve this via a suite of enzymes that involve a signal peptidase complex, prohormone convertases and carboxypeptidases. Using genome and transcriptome data of the demosponge Amphimedon queenslandica, a universal ancestor to metazoan multicellularity, we endeavour to bridge the evolution of precursor processing machinery from single-celled eukaryotic ancestors through to the complex multicellular organisms that compromise Metazoa. The precursor processing repertoire as defined in this study of A. queenslandica consists of 3 defined signal peptidase subunits, 6 prohormone convertases and 1 carboxypeptidase, with 2 putative duplicates identified for signal peptidase complex subunits. Analysis of their gene expression levels throughout the sponge development enabled us to predict levels of activity. Some A. queenslandica precursor processing components belong to established functional clades while others were identified as having novel, yet to be discovered roles. These findings have clarified the presence of precursor processing machinery in the poriferans, showing the necessary machinery for the removal of precursor sequences, a critical post-translational modification required by multicellular organisms, and further sets a foundation towards understanding the molecular mechanism for ancient protein processing.}, } @article {pmid31709760, year = {2019}, author = {Collens, A and Kelley, E and Katz, LA}, title = {The concept of the hologenome, an epigenetic phenomenon, challenges aspects of the modern evolutionary synthesis.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {8}, pages = {349-355}, pmid = {31709760}, issn = {1552-5015}, support = {R15 GM113177/GM/NIGMS NIH HHS/United States ; R15 HG010409/HG/NHGRI NIH HHS/United States ; }, mesh = {Adaptation, Biological ; *Biological Evolution ; *Epigenesis, Genetic ; Genome ; Microbiota ; Symbiosis/*genetics ; }, abstract = {John Tyler Bonner's call to re-evaluate evolutionary theory in light of major transitions in life on Earth (e.g., from the first origins of microbial life to the evolution of sex, and the origins of multicellularity) resonate with recent discoveries on epigenetics and the concept of the hologenome. Current studies of genome evolution often mistakenly focus only on the inheritance of DNA between parent and offspring. These are in line with the widely accepted Neo-Darwinian framework that pairs Mendelian genetics with an emphasis on natural selection as explanations for the evolution of biodiversity on Earth. Increasing evidence for widespread symbioses complicates this narrative, as is seen in Scott Gilbert's discussion of the concept of the holobiont in this series: Organisms across the tree of life coexist with substantial influence on one another through endosymbiosis, symbioses, and host-associated microbiomes. The holobiont theory, coupled with observations from molecular studies, also requires us to understand genomes in a new way-by considering the interactions underlain by the genome of a host plus its associated microbes, a conglomerate entity referred to as the hologenome. We argue that the complex patterns of inheritance of these genomes coupled with the influence of symbionts on host gene expression make the concept of the hologenome an epigenetic phenomenon. We further argue that the aspects of the hologenome challenge of the modern evolutionary synthesis, which requires updating to remain consistent with Darwin's intent of providing natural laws that underlie the evolution of life on Earth.}, } @article {pmid31707219, year = {2019}, author = {Stubbendieck, RM and Li, H and Currie, CR}, title = {Convergent evolution of signal-structure interfaces for maintaining symbioses.}, journal = {Current opinion in microbiology}, volume = {50}, number = {}, pages = {71-78}, pmid = {31707219}, issn = {1879-0364}, support = {T15 LM007359/LM/NLM NIH HHS/United States ; U19 AI109673/AI/NIAID NIH HHS/United States ; U19 TW009872/TW/FIC NIH HHS/United States ; }, mesh = {Animals ; Ants/microbiology ; Decapodiformes/microbiology ; *Evolution, Molecular ; Fabaceae/microbiology ; *Host Microbial Interactions ; Humans ; *Microbiota ; *Symbiosis ; }, abstract = {Symbiotic microbes are essential to the ecological success and evolutionary diversification of multicellular organisms. The establishment and stability of bipartite symbioses are shaped by mechanisms ensuring partner fidelity between host and symbiont. In this minireview, we demonstrate how the interface of chemical signals and host structures influences fidelity between legume root nodules and rhizobia, Hawaiian bobtail squid light organs and Allivibrio fischeri, and fungus-growing ant crypts and Pseudonocardia. Subsequently, we illustrate the morphological diversity and widespread phylogenetic distribution of specialized structures used by hosts to house microbial symbionts, indicating the importance of signal-structure interfaces across the history of multicellular life. These observations, and the insights garnered from well-studied bipartite associations, demonstrate the need to concentrate on the signal-structure interface in complex and multipartite systems, including the human microbiome.}, } @article {pmid31702845, year = {2020}, author = {Grall, E and Tschopp, P}, title = {A sense of place, many times over - pattern formation and evolution of repetitive morphological structures.}, journal = {Developmental dynamics : an official publication of the American Association of Anatomists}, volume = {249}, number = {3}, pages = {313-327}, doi = {10.1002/dvdy.131}, pmid = {31702845}, issn = {1097-0177}, mesh = {Animals ; Body Patterning/genetics/*physiology ; Gene Expression Regulation, Developmental/genetics/*physiology ; Humans ; Morphogenesis/genetics/*physiology ; Signal Transduction/genetics/*physiology ; }, abstract = {Fifty years ago, Lewis Wolpert introduced the concept of "positional information" to explain how patterns form in a multicellular embryonic field. Using morphogen gradients, whose continuous distributions of positional values are discretized via thresholds into distinct cellular states, he provided, at the theoretical level, an elegant solution to the "French Flag problem." In the intervening years, many experimental studies have lent support to Wolpert's ideas. However, the embryonic patterning of highly repetitive morphological structures, as often occurring in nature, can reveal limitations in the strict implementation of his initial theory, given the number of distinct threshold values that would have to be specified. Here, we review how positional information is complemented to circumvent these inadequacies, to accommodate tissue growth and pattern periodicity. In particular, we focus on functional anatomical assemblies composed of such structures, like the vertebrate spine or tetrapod digits, where the resulting segmented architecture is intrinsically linked to periodic pattern formation and unidirectional growth. These systems integrate positional information and growth with additional patterning cues that, we suggest, increase robustness and evolvability. We discuss different experimental and theoretical models to study such patterning systems, and how the underlying processes are modulated over evolutionary timescales to enable morphological diversification.}, } @article {pmid31700531, year = {2019}, author = {Raven, N and Bramwell, G and Hamede, R and Thomas, F and Ujvari, B}, title = {Fifth International Biannual Evolution and Ecology of Cancer Conference (Cooperation, Conflict and Parasitism) meeting report-Wellcome Genome Campus, Hinxton, UK.}, journal = {Evolutionary applications}, volume = {12}, number = {10}, pages = {1863-1867}, doi = {10.1111/eva.12862}, pmid = {31700531}, issn = {1752-4571}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {The fifth biannual conference of the International Society of Evolution and Ecology of Cancer (ISEEC) was held between the 17th and 19th of July 2019 in Hinxton (UK) at the Wellcome Genome Campus. The main theme of the conference: cooperation, conflict and parasitism reflected our growing understanding of the role cancer has played in the evolution of multicellular organisms, as well as the urgent need of translating these Darwinian processes to treatment strategies. Below we provide a brief summary of each plenary sessions and other oral presentations, to bring the conference to the broader audience of evolutionary biology and applications.}, } @article {pmid31689405, year = {2019}, author = {Coudert, Y and Harris, S and Charrier, B}, title = {Design Principles of Branching Morphogenesis in Filamentous Organisms.}, journal = {Current biology : CB}, volume = {29}, number = {21}, pages = {R1149-R1162}, doi = {10.1016/j.cub.2019.09.021}, pmid = {31689405}, issn = {1879-0445}, mesh = {Ascomycota/*growth & development ; *Body Patterning ; Bryopsida/*growth & development ; Phaeophyta/*growth & development ; }, abstract = {The radiation of life on Earth was accompanied by the diversification of multicellular body plans in the eukaryotic kingdoms Animalia, Plantae, Fungi and Chromista. Branching forms are ubiquitous in nature and evolved repeatedly in the above lineages. The developmental and genetic basis of branch formation is well studied in the three-dimensional shoot and root systems of land plants, and in animal organs such as the lung, kidney, mammary gland, vasculature, etc. Notably, recent thought-provoking studies combining experimental analysis and computational modeling of branching patterns in whole animal organs have identified global patterning rules and proposed unifying principles of branching morphogenesis. Filamentous branching forms represent one of the simplest expressions of the multicellular body plan and constitute a key step in the evolution of morphological complexity. Similarities between simple and complex branching forms distantly related in evolution are compelling, raising the question whether shared mechanisms underlie their development. Here, we focus on filamentous branching organisms that represent major study models from three distinct eukaryotic kingdoms, including the moss Physcomitrella patens (Plantae), the brown alga Ectocarpus sp. (Chromista), and the ascomycetes Neurospora crassa and Aspergillus nidulans (Fungi), and bring to light developmental regulatory mechanisms and design principles common to these lineages. Throughout the review we explore how the regulatory mechanisms of branching morphogenesis identified in other models, and in particular animal organs, may inform our thinking on filamentous systems and thereby advance our understanding of the diverse strategies deployed across the eukaryotic tree of life to evolve similar forms.}, } @article {pmid31687086, year = {2019}, author = {Poljsak, B and Kovac, V and Dahmane, R and Levec, T and Starc, A}, title = {Cancer Etiology: A Metabolic Disease Originating from Life's Major Evolutionary Transition?.}, journal = {Oxidative medicine and cellular longevity}, volume = {2019}, number = {}, pages = {7831952}, pmid = {31687086}, issn = {1942-0994}, mesh = {Animals ; *Biological Evolution ; Drug Resistance, Neoplasm ; Energy Metabolism ; Humans ; Metabolic Diseases/*etiology ; Mitochondria/metabolism ; Neoplasms/*etiology ; }, abstract = {A clear understanding of the origins of cancer is the basis of successful strategies for effective cancer prevention and management. The origin of cancer at the molecular and cellular levels is not well understood. Is the primary cause of the origin of cancer the genomic instability or impaired energy metabolism? An attempt was made to present cancer etiology originating from life's major evolutionary transition. The first evolutionary transition went from simple to complex cells when eukaryotic cells with glycolytic energy production merged with the oxidative mitochondrion (The Endosymbiosis Theory first proposed by Lynn Margulis in the 1960s). The second transition went from single-celled to multicellular organisms once the cells obtained mitochondria, which enabled them to obtain a higher amount of energy. Evidence will be presented that these two transitions, as well as the decline of NAD+ and ATP levels, are the root of cancer diseases. Restoring redox homeostasis and reactivation of mitochondrial oxidative metabolism are important factors in cancer prevention.}, } @article {pmid31681764, year = {2019}, author = {Naumann, B and Burkhardt, P}, title = {Spatial Cell Disparity in the Colonial Choanoflagellate Salpingoeca rosetta.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {231}, pmid = {31681764}, issn = {2296-634X}, abstract = {Choanoflagellates are the closest unicellular relatives of animals (Metazoa). These tiny protists display complex life histories that include sessile as well as different pelagic stages. Some choanoflagellates have the ability to form colonies as well. Up until recently, these colonies have been described to consist of mostly identical cells showing no spatial cell differentiation, which supported the traditional view that spatial cell differentiation, leading to the co-existence of specific cell types in animals, evolved after the split of the last common ancestor of the Choanoflagellata and Metazoa. The recent discovery of single cells in colonies of the choanoflagellate Salpingoeca rosetta that exhibit unique cell morphologies challenges this traditional view. We have now reanalyzed TEM serial sections, aiming to determine the degree of similarity of S. rosetta cells within a rosette colony. We investigated cell morphologies and nuclear, mitochondrial, and food vacuole volumes of 40 individual cells from four different S. rosetta rosette colonies and compared our findings to sponge choanocytes. Our analysis shows that cells in a choanoflagellate colony differ from each other in respect to cell morphology and content ratios of nuclei, mitochondria, and food vacuoles. Furthermore, cell disparity within S. rosetta colonies is slightly higher compared to cell disparity within sponge choanocytes. Moreover, we discovered the presence of plasma membrane contacts between colonial cells in addition to already described intercellular bridges and filo-/pseudopodial contacts. Our findings indicate that the last common ancestor of Choanoflagellata and Metazoa might have possessed plasma membrane contacts and spatial cell disparity during colonial life history stages.}, } @article {pmid31680996, year = {2019}, author = {Arnellos, A and Keijzer, F}, title = {Bodily Complexity: Integrated Multicellular Organizations for Contraction-Based Motility.}, journal = {Frontiers in physiology}, volume = {10}, number = {}, pages = {1268}, pmid = {31680996}, issn = {1664-042X}, abstract = {Compared to other forms of multicellularity, the animal case is unique. Animals-barring some exceptions-consist of collections of cells that are connected and integrated to such an extent that these collectives act as unitary, large free-moving entities capable of sensing macroscopic properties and events. This animal configuration is so well-known that it is often taken as a natural one that 'must' have evolved, given environmental conditions that make large free-moving units 'obviously' adaptive. Here we question the seemingly evolutionary inevitableness of animals and introduce a thesis of bodily complexity: The multicellular organization characteristic for typical animals requires the integration of a multitude of intrinsic bodily features between its sensorimotor, physiological, and developmental aspects, and the related contraction-based tissue- and cellular-level events and processes. The evolutionary road toward this bodily complexity involves, we argue, various intermediate organizational steps that accompany and support the wider transition from cilia-based to contraction/muscle-based motility, and which remain insufficiently acknowledged. Here, we stress the crucial and specific role played by muscle-based and myoepithelial tissue contraction-acting as a physical platform for organizing both the multicellular transmission of mechanical forces and multicellular signaling-as key foundation of animal motility, sensing and maintenance, and development. We illustrate and discuss these bodily features in the context of the four basal animal phyla-Porifera, Ctenophores, Placozoans, and Cnidarians-that split off before the bilaterians, a supergroup that incorporates all complex animals.}, } @article {pmid31673005, year = {2019}, author = {Brown, JL and Johnston, W and Delaney, C and Rajendran, R and Butcher, J and Khan, S and Bradshaw, D and Ramage, G and Culshaw, S}, title = {Biofilm-stimulated epithelium modulates the inflammatory responses in co-cultured immune cells.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {15779}, pmid = {31673005}, issn = {2045-2322}, support = {BB/P504567/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Bacteria/*immunology ; *Bacterial Physiological Phenomena ; Biofilms/*growth & development ; Coculture Techniques ; *Gingiva/immunology/microbiology/pathology ; Humans ; Inflammation/immunology/microbiology/pathology ; Inflammation Mediators/*immunology ; *Monocytes/immunology/microbiology/pathology ; *Mouth Mucosa/immunology/microbiology/pathology ; }, abstract = {The gingival epithelium is a physical and immunological barrier to the microbiota of the oral cavity, which interact through soluble mediators with the immune cells that patrol the tissue at the gingival epithelium. We sought to develop a three-dimensional gingivae-biofilm interface model using a commercially available gingival epithelium to study the tissue inflammatory response to oral biofilms associated with "health", "gingivitis" and "periodontitis". These biofilms were developed by sequential addition of microorganisms to mimic the formation of supra- and sub-gingival plaque in vivo. Secondly, to mimic the interactions between gingival epithelium and immune cells in vivo, we integrated peripheral blood mononuclear cells and CD14[+] monocytes into our three-dimensional model and were able to assess the inflammatory response in the immune cells cultured with and without gingival epithelium. We describe a differential inflammatory response in immune cells cultured with epithelial tissue, and more so following incubation with epithelium stimulated by "gingivitis-associated" biofilm. These results suggest that gingival epithelium-derived soluble mediators may control the inflammatory status of immune cells in vitro, and therefore targeting of the epithelial response may offer novel therapies. This multi-cellular interface model, both of microbial and host origin, offers a robust in vitro platform to investigate host-pathogens at the epithelial surface.}, } @article {pmid31667165, year = {2019}, author = {Fortunato, A and Aktipis, A}, title = {Social feeding behavior of Trichoplax adhaerens.}, journal = {Frontiers in ecology and evolution}, volume = {7}, number = {}, pages = {}, pmid = {31667165}, issn = {2296-701X}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; }, abstract = {Animals have evolved different foraging strategies in which some animals forage independently and others forage in groups. The evolution of social feeding does not necessarily require cooperation; social feeding can be a beneficial individual-level strategy if it provides mutualistic benefits, for example though increasing the efficiency of resource extraction or processing. We found that Trichoplax adhaerens, the simplest multicellular animal ever described, engages in social feeding behavior. T. adhaerens lacks muscle tissue, nervous and digestive systems - yet is capable of aggregating and forming groups of closely connected individuals who collectively feed. The tight physical interactions between the animals are transitory and appear to serve the goal of staying connected to neighbors during the external digestion of algae when enzymes are released on the biofilm and nutrients are absorbed through the ventral epithelium. We found that T. adhaerens are more likely to engage in social feeding when the concentrations of algae are high - both in a semi-natural conditions and in vitro. It is surprising that T. adhaerens - an organism without a nervous system - is able to engage in this social feeding behavior. Whether this behavior is cooperative is still an open question. Nevertheless, the social feeding behavior of T. adhaerens, an early multicellular animal, suggests that sociality may have played an important role in the early evolution of animals. It also suggests that T. adhaerens could be used as a simple model organism for exploring questions regarding ecology and sociobiology.}, } @article {pmid31662428, year = {2019}, author = {Du, H and Zhang, W and Zhang, W and Zhang, W and Pan, H and Pan, Y and Bazylinski, DA and Wu, LF and Xiao, T and Lin, W}, title = {Magnetosome Gene Duplication as an Important Driver in the Evolution of Magnetotaxis in the Alphaproteobacteria.}, journal = {mSystems}, volume = {4}, number = {5}, pages = {}, pmid = {31662428}, issn = {2379-5077}, abstract = {The evolution of microbial magnetoreception (or magnetotaxis) is of great interest in the fields of microbiology, evolutionary biology, biophysics, geomicrobiology, and geochemistry. Current genomic data from magnetotactic bacteria (MTB), the only prokaryotes known to be capable of sensing the Earth's geomagnetic field, suggests an ancient origin of magnetotaxis in the domain Bacteria Vertical inheritance, followed by multiple independent magnetosome gene cluster loss, is considered to be one of the major forces that drove the evolution of magnetotaxis at or above the class or phylum level, although the evolutionary trajectories at lower taxonomic ranks (e.g., within the class level) remain largely unstudied. Here we report the isolation, cultivation, and sequencing of a novel magnetotactic spirillum belonging to the genus Terasakiella (Terasakiella sp. strain SH-1) within the class Alphaproteobacteria The complete genome sequence of Terasakiella sp. strain SH-1 revealed an unexpected duplication event of magnetosome genes within the mamAB operon, a group of genes essential for magnetosome biomineralization and magnetotaxis. Intriguingly, further comparative genomic analysis suggests that the duplication of mamAB genes is a common feature in the genomes of alphaproteobacterial MTB. Taken together, with the additional finding that gene duplication appears to have also occurred in some magnetotactic members of the Deltaproteobacteria, our results indicate that gene duplication plays an important role in the evolution of magnetotaxis in the Alphaproteobacteria and perhaps the domain Bacteria IMPORTANCE A diversity of organisms can sense the geomagnetic field for the purpose of navigation. Magnetotactic bacteria are the most primitive magnetism-sensing organisms known thus far and represent an excellent model system for the study of the origin, evolution, and mechanism of microbial magnetoreception (or magnetotaxis). The present study is the first report focused on magnetosome gene cluster duplication in the Alphaproteobacteria, which suggests the important role of gene duplication in the evolution of magnetotaxis in the Alphaproteobacteria and perhaps the domain Bacteria A novel scenario for the evolution of magnetotaxis in the Alphaproteobacteria is proposed and may provide new insights into evolution of magnetoreception of higher species.}, } @article {pmid31649660, year = {2019}, author = {Smith, NC and Rise, ML and Christian, SL}, title = {A Comparison of the Innate and Adaptive Immune Systems in Cartilaginous Fish, Ray-Finned Fish, and Lobe-Finned Fish.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {2292}, pmid = {31649660}, issn = {1664-3224}, mesh = {*Adaptive Immunity ; Animals ; *Evolution, Molecular ; Fish Proteins/genetics/immunology ; *Immunity, Innate ; Immunoglobulins/genetics/immunology ; Leukocytes/*immunology ; Major Histocompatibility Complex/genetics/immunology ; Skates, Fish/genetics/*immunology ; Species Specificity ; }, abstract = {The immune system is composed of two subsystems-the innate immune system and the adaptive immune system. The innate immune system is the first to respond to pathogens and does not retain memory of previous responses. Innate immune responses are evolutionarily older than adaptive responses and elements of innate immunity can be found in all multicellular organisms. If a pathogen persists, the adaptive immune system will engage the pathogen with specificity and memory. Several components of the adaptive system including immunoglobulins (Igs), T cell receptors (TCR), and major histocompatibility complex (MHC), are assumed to have arisen in the first jawed vertebrates-the Gnathostomata. This review will discuss and compare components of both the innate and adaptive immune systems in Gnathostomes, particularly in Chondrichthyes (cartilaginous fish) and in Osteichthyes [bony fish: the Actinopterygii (ray-finned fish) and the Sarcopterygii (lobe-finned fish)]. While many elements of both the innate and adaptive immune systems are conserved within these species and with higher level vertebrates, some elements have marked differences. Components of the innate immune system covered here include physical barriers, such as the skin and gastrointestinal tract, cellular components, such as pattern recognition receptors and immune cells including macrophages and neutrophils, and humoral components, such as the complement system. Components of the adaptive system covered include the fundamental cells and molecules of adaptive immunity: B lymphocytes (B cells), T lymphocytes (T cells), immunoglobulins (Igs), and major histocompatibility complex (MHC). Comparative studies in fish such as those discussed here are essential for developing a comprehensive understanding of the evolution of the immune system.}, } @article {pmid31649059, year = {2019}, author = {Duttke, SH and Chang, MW and Heinz, S and Benner, C}, title = {Identification and dynamic quantification of regulatory elements using total RNA.}, journal = {Genome research}, volume = {29}, number = {11}, pages = {1836-1846}, pmid = {31649059}, issn = {1549-5469}, support = {U19 AI106754/AI/NIAID NIH HHS/United States ; U19 AI135972/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Gene Regulatory Networks ; Histones/metabolism ; Mice ; Mice, Inbred C57BL ; RNA/*genetics ; RNA Caps ; Transcription Factors/metabolism ; Transcription, Genetic ; }, abstract = {The spatial and temporal regulation of transcription initiation is pivotal for controlling gene expression. Here, we introduce capped-small RNA-seq (csRNA-seq), which uses total RNA as starting material to detect transcription start sites (TSSs) of both stable and unstable RNAs at single-nucleotide resolution. csRNA-seq is highly sensitive to acute changes in transcription and identifies an order of magnitude more regulated transcripts than does RNA-seq. Interrogating tissues from species across the eukaryotic kingdoms identified unstable transcripts resembling enhancer RNAs, pri-miRNAs, antisense transcripts, and promoter upstream transcripts in multicellular animals, plants, and fungi spanning 1.6 billion years of evolution. Integration of epigenomic data from these organisms revealed that histone H3 trimethylation (H3K4me3) was largely confined to TSSs of stable transcripts, whereas H3K27ac marked nucleosomes downstream from all active TSSs, suggesting an ancient role for posttranslational histone modifications in transcription. Our findings show that total RNA is sufficient to identify transcribed regulatory elements and capture the dynamics of initiated stable and unstable transcripts at single-nucleotide resolution in eukaryotes.}, } @article {pmid31647412, year = {2019}, author = {Dudin, O and Ondracka, A and Grau-Bové, X and Haraldsen, AA and Toyoda, A and Suga, H and Bråte, J and Ruiz-Trillo, I}, title = {A unicellular relative of animals generates a layer of polarized cells by actomyosin-dependent cellularization.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {31647412}, issn = {2050-084X}, support = {Consolidator Grant ERC-2012-Co-616960/ERC_/European Research Council/International ; MEXT KAKENHI 221S0002//Ministry of Education, Culture, Sports, Science and Technology/International ; MEXT KAKENHI 26891021//Ministry of Education, Culture, Sports, Science and Technology/International ; Young Research Talents grant 240284//Research Council of Norway/International ; P2LAP3_171815/SNSF_/Swiss National Science Foundation/Switzerland ; Individual fellowship MSCA-IF 746044//H2020 Marie Skłodowska-Curie Actions/International ; Individual fellowship MSCA-IF 747086//H2020 Marie Skłodowska-Curie Actions/International ; ERC-2012-Co -616960//European Research Council Consolidator Grant/International ; 221S0002//MEXT KAKENHI/International ; 26891021//MEXT KAKENHI/International ; 240284//Young Research Talents grant from the Research Council of Norway/International ; MSCA-IF 746044//Marie Sklodowska-Curie individual fellowship/International ; MSCA-IF 747086//Marie Sklodowska-Curie individual fellowship/International ; }, mesh = {Actomyosin/*metabolism ; Animals ; Cell Membrane/*metabolism ; *Cell Polarity ; Gene Expression Regulation ; Mesomycetozoea/*physiology ; }, abstract = {In animals, cellularization of a coenocyte is a specialized form of cytokinesis that results in the formation of a polarized epithelium during early embryonic development. It is characterized by coordinated assembly of an actomyosin network, which drives inward membrane invaginations. However, whether coordinated cellularization driven by membrane invagination exists outside animals is not known. To that end, we investigate cellularization in the ichthyosporean Sphaeroforma arctica, a close unicellular relative of animals. We show that the process of cellularization involves coordinated inward plasma membrane invaginations dependent on an actomyosin network and reveal the temporal order of its assembly. This leads to the formation of a polarized layer of cells resembling an epithelium. We show that this stage is associated with tightly regulated transcriptional activation of genes involved in cell adhesion. Hereby we demonstrate the presence of a self-organized, clonally-generated, polarized layer of cells in a unicellular relative of animals.}, } @article {pmid31633482, year = {2019}, author = {Murphy, DP and Hughes, AE and Lawrence, KA and Myers, CA and Corbo, JC}, title = {Cis-regulatory basis of sister cell type divergence in the vertebrate retina.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {31633482}, issn = {2050-084X}, support = {T32 EY013360/EY/NEI NIH HHS/United States ; T32EY013360/EY/NEI NIH HHS/United States ; R01EY024958/EY/NEI NIH HHS/United States ; R01EY026672/EY/NEI NIH HHS/United States ; R01 EY024958/EY/NEI NIH HHS/United States ; F32EY029571/EY/NEI NIH HHS/United States ; F32 EY029571/EY/NEI NIH HHS/United States ; R01EY025196/EY/NEI NIH HHS/United States ; R01 EY025196/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; Chromatin/metabolism ; *Evolution, Molecular ; Gene Expression Profiling ; *Gene Regulatory Networks ; Mice ; Photoreceptor Cells/*physiology ; Regulatory Sequences, Nucleic Acid/*genetics ; Retinal Bipolar Cells/*physiology ; }, abstract = {Multicellular organisms evolved via repeated functional divergence of transcriptionally related sister cell types, but the mechanisms underlying sister cell type divergence are not well understood. Here, we study a canonical pair of sister cell types, retinal photoreceptors and bipolar cells, to identify the key cis-regulatory features that distinguish them. By comparing open chromatin maps and transcriptomic profiles, we found that while photoreceptor and bipolar cells have divergent transcriptomes, they share remarkably similar cis-regulatory grammars, marked by enrichment of K50 homeodomain binding sites. However, cell class-specific enhancers are distinguished by enrichment of E-box motifs in bipolar cells, and Q50 homeodomain motifs in photoreceptors. We show that converting K50 motifs to Q50 motifs represses reporter expression in bipolar cells, while photoreceptor expression is maintained. These findings suggest that partitioning of Q50 motifs within cell type-specific cis-regulatory elements was a critical step in the evolutionary divergence of the bipolar transcriptome from that of photoreceptors.}, } @article {pmid31624206, year = {2019}, author = {Brunet, T and Larson, BT and Linden, TA and Vermeij, MJA and McDonald, K and King, N}, title = {Light-regulated collective contractility in a multicellular choanoflagellate.}, journal = {Science (New York, N.Y.)}, volume = {366}, number = {6463}, pages = {326-334}, doi = {10.1126/science.aay2346}, pmid = {31624206}, issn = {1095-9203}, mesh = {Actomyosin/metabolism ; Animals ; Biological Evolution ; Choanoflagellata/cytology/*physiology ; Cyclic GMP/metabolism ; *Light ; Microvilli/physiology ; Movement ; Phosphoric Diester Hydrolases/metabolism ; Protozoan Proteins/metabolism ; Sensory Rhodopsins/metabolism ; }, abstract = {Collective cell contractions that generate global tissue deformations are a signature feature of animal movement and morphogenesis. However, the origin of collective contractility in animals remains unclear. While surveying the Caribbean island of Curaçao for choanoflagellates, the closest living relatives of animals, we isolated a previously undescribed species (here named Choanoeca flexa sp. nov.) that forms multicellular cup-shaped colonies. The colonies rapidly invert their curvature in response to changing light levels, which they detect through a rhodopsin-cyclic guanosine monophosphate pathway. Inversion requires actomyosin-mediated apical contractility and allows alternation between feeding and swimming behavior. C. flexa thus rapidly converts sensory inputs directly into multicellular contractions. These findings may inform reconstructions of hypothesized animal ancestors that existed before the evolution of specialized sensory and contractile cells.}, } @article {pmid31617664, year = {2019}, author = {Nanjundiah, V}, title = {Many roads lead to Rome: Neutral phenotypes in microorganisms.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {8}, pages = {339-348}, doi = {10.1002/jez.b.22909}, pmid = {31617664}, issn = {1552-5015}, mesh = {3',5'-Cyclic-AMP Phosphodiesterases ; Adaptation, Biological ; *Biological Evolution ; Dictyostelium/enzymology/*physiology ; *Phenotype ; }, abstract = {John Bonner pointed out that microorganisms differ in several ways, some of which may reflect neutral phenotypic evolution. For making his case, Bonner referred to interspecies differences and morphological traits. Here we consider intraspecies differences and physiological traits. As a case-study, we examine the production of an extracellular cyclic 3 ' ,5 ' monophosphate phosphodiesterase in the cellular slime mold Dictyostelium discoideum. Temporal profiles of phosphodiesterase activity differ significantly between wild-type strains. From that we argue that the inference drawn initially from studies on a single wild-type, namely that the profile displayed by it pointed to an adaptive role, was mistaken. We generalize the conclusion to suggest that physiological differences exhibited by microorganisms of the same species may, but need not, reflect adaptations to different environments. Rather, the differences could be related to the fact that microorganisms live in groups whose composition can vary between homogeneous (clonal) and heterogeneous (polyclonal). More than one physiological profile is consistent with the normal development of the group in a given environment; the alternatives are neutral. When studying microbial physiology and behavior, it is expected that the observations are made on a clonal population; genetic (and so phenotypic) heterogeneity is carefully guarded against. As the example from D. discoideum shows, an unintended consequence of overlooking phenotypic heterogeneity is that one can fall into the trap of accepting a seemingly plausible, but possibly erroneous, adaptive explanation for a "normal" wild-type phenotype.}, } @article {pmid31615963, year = {2019}, author = {Blank-Landeshammer, B and Teichert, I and Märker, R and Nowrousian, M and Kück, U and Sickmann, A}, title = {Combination of Proteogenomics with Peptide De Novo Sequencing Identifies New Genes and Hidden Posttranscriptional Modifications.}, journal = {mBio}, volume = {10}, number = {5}, pages = {}, pmid = {31615963}, issn = {2150-7511}, mesh = {Alternative Splicing/*genetics ; Genome, Fungal/*genetics ; Molecular Sequence Annotation ; Peptides/*metabolism ; Phylogeny ; Proteogenomics/*methods ; }, abstract = {Proteogenomics combines proteomics, genomics, and transcriptomics and has considerably improved genome annotation in poorly investigated phylogenetic groups for which homology information is lacking. Furthermore, it can be advantageous when reinvestigating well-annotated genomes. Here, we applied an advanced proteogenomics approach, combining standard proteogenomics with peptide de novo sequencing, to refine annotation of the well-studied model fungus Sordaria macrospora We investigated samples from different developmental and physiological conditions, resulting in the detection of 104 so-far hidden proteins and annotation changes in 575 genes, including 389 splice site refinements. Significantly, our approach provides peptide-level evidence for 113 single-amino-acid variations and 15 C-terminal protein elongations originating from A-to-I RNA editing, a phenomenon recently detected in fungi. Coexpression and phylostratigraphic analysis of the refined proteome suggest that new functions in evolutionarily young genes correlate with distinct developmental stages. In conclusion, our advanced proteogenomics approach supports and promotes functional studies of fungal model systems.IMPORTANCE Next-generation sequencing techniques have considerably increased the number of completely sequenced eukaryotic genomes. These genomes are mostly automatically annotated, and ab initio gene prediction is commonly combined with homology-based search approaches and often supported by transcriptomic data. The latter in particular improve the prediction of intron splice sites and untranslated regions. However, correct prediction of translation initiation sites (TIS), alternative splice junctions, and protein-coding potential remains challenging. Here, we present an advanced proteogenomics approach, namely, the combination of proteogenomics and de novo peptide sequencing analysis, in conjunction with Blast2GO and phylostratigraphy. Using the model fungus Sordaria macrospora as an example, we provide a comprehensive view of the proteome that not only increases the functional understanding of this multicellular organism at different developmental stages but also immensely enhances the genome annotation quality.}, } @article {pmid31613422, year = {2019}, author = {Love, AC}, title = {Evolution evolving? Reflections on big questions.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {8}, pages = {315-320}, doi = {10.1002/jez.b.22907}, pmid = {31613422}, issn = {1552-5015}, mesh = {*Biological Evolution ; Developmental Biology ; Selection, Genetic ; }, abstract = {John Bonner managed a long and productive career that balanced specialized inquiry into cellular slime molds with general investigations of big questions in evolutionary biology, such as the origins of multicellular development and the evolution of complexity. This commentary engages with his final paper ("The evolution of evolution"), which argues that the evolutionary process has changed through the history of life. In particular, Bonner emphasizes the possibility that natural selection plays different roles at different size scales. I identify some underlying assumptions in his argument and evaluate its cogency to both foster future discussion and emulate the intellectual example set by Bonner over a lifetime. This endeavor is important beyond Bonner's own theoretical disposition because similar issues are visible in controversies about the possibility of an extended evolutionary synthesis.}, } @article {pmid31610128, year = {2020}, author = {Jasper, H}, title = {Intestinal Stem Cell Aging: Origins and Interventions.}, journal = {Annual review of physiology}, volume = {82}, number = {}, pages = {203-226}, doi = {10.1146/annurev-physiol-021119-034359}, pmid = {31610128}, issn = {1545-1585}, mesh = {Aging/*physiology ; Animals ; Cellular Senescence/*physiology ; Epithelial Cells/physiology ; Humans ; Intestinal Mucosa/chemistry/physiology ; Intestines/*cytology/*physiology ; Regeneration/physiology ; Stem Cells/*physiology ; }, abstract = {Regenerative processes that maintain the function of the gastrointestinal (GI) epithelium are critical for health and survival of multicellular organisms. In insects and vertebrates, intestinal stem cells (ISCs) regenerate the GI epithelium. ISC function is regulated by intrinsic, local, and systemic stimuli to adjust regeneration to tissue demands. These control mechanisms decline with age, resulting in significant perturbation of intestinal homeostasis. Processes that lead to this decline have been explored intensively in Drosophila melanogaster in recent years and are now starting to be characterized in mammalian models. This review presents a model for age-related regenerative decline in the fly intestine and discusses recent findings that start to establish molecular mechanisms of age-related decline of mammalian ISC function.}, } @article {pmid31604443, year = {2019}, author = {Ramon-Mateu, J and Ellison, ST and Angelini, TE and Martindale, MQ}, title = {Regeneration in the ctenophore Mnemiopsis leidyi occurs in the absence of a blastema, requires cell division, and is temporally separable from wound healing.}, journal = {BMC biology}, volume = {17}, number = {1}, pages = {80}, pmid = {31604443}, issn = {1741-7007}, mesh = {Animals ; Body Patterning ; Cell Proliferation ; Ctenophora/*physiology ; Models, Biological ; *Regeneration ; *Wound Healing ; }, abstract = {BACKGROUND: The ability to regenerate is a widely distributed but highly variable trait among metazoans. A variety of modes of regeneration has been described for different organisms; however, many questions regarding the origin and evolution of these strategies remain unanswered. Most species of ctenophore (or "comb jellies"), a clade of marine animals that branch off at the base of the animal tree of life, possess an outstanding capacity to regenerate. However, the cellular and molecular mechanisms underlying this ability are unknown. We have used the ctenophore Mnemiopsis leidyi as a system to study wound healing and adult regeneration and provide some first-time insights of the cellular mechanisms involved in the regeneration of one of the most ancient extant group of multicellular animals.

RESULTS: We show that cell proliferation is activated at the wound site and is indispensable for whole-body regeneration. Wound healing occurs normally in the absence of cell proliferation forming a scar-less wound epithelium. No blastema-like structure is generated at the cut site, and pulse-chase experiments and surgical intervention show that cells originating in the main regions of cell proliferation (the tentacle bulbs) do not seem to contribute to the formation of new structures after surgical challenge, suggesting a local source of cells during regeneration. While exposure to cell-proliferation blocking treatment inhibits regeneration, the ability to regenerate is recovered when the treatment ends (days after the original cut), suggesting that ctenophore regenerative capabilities are constantly ready to be triggered and they are somehow separable of the wound healing process.

CONCLUSIONS: Ctenophore regeneration takes place through a process of cell proliferation-dependent non-blastemal-like regeneration and is temporally separable of the wound healing process. We propose that undifferentiated cells assume the correct location of missing structures and differentiate in place. The remarkable ability to replace missing tissue, the many favorable experimental features (e.g., optical clarity, high fecundity, rapid regenerative performance, stereotyped cell lineage, sequenced genome), and the early branching phylogenetic position in the animal tree, all point to the emergence of ctenophores as a new model system to study the evolution of animal regeneration.}, } @article {pmid36658830, year = {2018}, author = {Sui, Y and Huang, C and Zhang, R and Wang, Z and Ogg, J and Kemp, DB}, title = {Astronomical time scale for the lower Doushantuo Formation of early Ediacaran, South China.}, journal = {Science bulletin}, volume = {63}, number = {22}, pages = {1485-1494}, doi = {10.1016/j.scib.2018.10.010}, pmid = {36658830}, issn = {2095-9281}, abstract = {Nearly 90% of the Ediacaran Period (635-541 Ma) of the Neoproterozoic is represented by the Doushantuo Formation (DST Fm) in South China. Its lowest Member I is a 3.7 m-thick cap carbonate deposited at the termination of the Cryogenian Marinoan glaciation. The DST Fm consists of alternating organic-rich black shale and thinly bedded dolostone, and it contains some of the oldest records of multi-cellular life and three pronounced negative carbon isotope excursions. The Jiulongwan (JLW) section is a well-studied reference section for these Ediacaran events. Spectral analysis of geochemical data through the lower DST Fm (22.3 m) shows 27 predominant ∼90 cm sedimentary cycles that correspond to 405-ka long eccentricity cycles. The power spectra of the 405-ka tuned Ca and Fe/Ti series show significant peaks at ∼1.2-Ma, 405-ka, 133-ka, 128-ka, 100-ka, 82-ka, ∼31-ka and 29-ka periods, respectively. A 11.16 Ma-long astronomical time scale has been constructed for the lower DST Fm and provide a duration of 1.6 Ma for the cap carbonate (Member I) based on the 405-ka long eccentricity cycle tuning. Using the U-Pb age of 635.2 ± 0.6 Ma for the volcanic ash bed at the Member I/II boundary, we proposed a 636.8 Ma age for the base of the DST Fm. These ages and astronomical timescale provide important new constraints on the subdivision of Ediacaran strata, and have implications for understanding the character of the first negative δ[13]C excursion (EN1). Orbital forcing may have been played an important role for the climate changes and the evolution of Ediacaran multi-cellular life and the carbon cycle variations.}, } @article {pmid32412616, year = {2018}, author = {Xiao, S and Tang, Q}, title = {After the boring billion and before the freezing millions: evolutionary patterns and innovations in the Tonian Period.}, journal = {Emerging topics in life sciences}, volume = {2}, number = {2}, pages = {161-171}, doi = {10.1042/ETLS20170165}, pmid = {32412616}, issn = {2397-8554}, abstract = {The Tonian Period (ca. 1000-720 Ma) follows the 'boring billion' in the Mesoproterozoic Era and precedes 'snowball Earth' glaciations in the Cryogenian Period. It represents a critical transition in Earth history. Geochemical data indicate that the Tonian Period may have witnessed a significant increase in atmospheric pO2 levels and a major transition from predominantly sulfidic to ferruginous mid-depth seawaters. Molecular clock estimates suggest that early animals may have diverged in the Tonian Period, raising the intriguing possibility of coupled environmental changes and evolutionary innovations. The co-evolution of life and its environment during the Tonian Period can be tested against the fossil record by examining diversity trends in the Proterozoic and evolutionary innovations in the Tonian. Compilations of Proterozoic microfossils and macrofossils apparently support a Tonian increase in global taxonomic diversity and morphological range relative to the Mesoproterozoic Era, although this is not reflected in assemblage-level diversity patterns. The fossil record suggests that major eukaryote groups (including Opisthokonta, Amoebozoa, Plantae, and SAR) may have diverged and important evolutionary innovations (e.g. multicellularity and cell differentiation in several groups, eukaryovory, eukaryote biomineralization, and heterocystous cyanobacteria) may have arisen by the Tonian Period, but thus far no convincing animal fossils have been found in the Tonian. Tonian paleontology is still in its nascent stage, and it offers many opportunities to explore Earth-life evolution in this critical geological period.}, } @article {pmid32412615, year = {2018}, author = {Mills, DB and Francis, WR and Canfield, DE}, title = {Animal origins and the Tonian Earth system.}, journal = {Emerging topics in life sciences}, volume = {2}, number = {2}, pages = {289-298}, doi = {10.1042/ETLS20170160}, pmid = {32412615}, issn = {2397-8554}, abstract = {The Neoproterozoic Era (1000-541 million years ago, Ma) was characterized by dramatic environmental and evolutionary change, including at least two episodes of extensive, low-latitude glaciation, potential changes in the redox structure of the global ocean, and the origin and diversification of animal life. How these different events related to one another remains an active area of research, particularly how these environmental changes influenced, and were influenced by, the earliest evolution of animals. Animal multicellularity is estimated to have evolved in the Tonian Period (1000-720 Ma) and represents one of at least six independent acquisitions of complex multicellularity, characterized by cellular differentiation, three-dimensional body plans, and active nutrient transport. Compared with the other instances of complex multicellularity, animals represent the only clade to have evolved from wall-less, phagotrophic flagellates, which likely placed unique cytological and trophic constraints on the evolution of animal multicellularity. Here, we compare recent molecular clock estimates with compilations of the chromium isotope, micropaleontological, and organic biomarker records, suggesting that, as of now, the origin of animals was not obviously correlated to any environmental-ecological change in the Tonian Period. This lack of correlation is consistent with the idea that the evolution of animal multicellularity was primarily dictated by internal, developmental constraints and occurred independently of the known environmental-ecological changes that characterized the Neoproterozoic Era.}, } @article {pmid31723354, year = {2018}, author = {Jacobeen, S and Pentz, JT and Graba, EC and Brandys, CG and Ratcliff, WC and Yunker, PJ}, title = {Cellular packing, mechanical stress and the evolution of multicellularity.}, journal = {Nature physics}, volume = {14}, number = {}, pages = {286-290}, pmid = {31723354}, issn = {1745-2473}, support = {NNX15AR33G/NASA/NASA/United States ; }, abstract = {The evolution of multicellularity set the stage for sustained increases in organismal complexity[1-5]. However, a fundamental aspect of this transition remains largely unknown: how do simple clusters of cells evolve increased size when confronted by forces capable of breaking intracellular bonds? Here we show that multicellular snowflake yeast clusters[6-8] fracture due to crowding-induced mechanical stress. Over seven weeks (~291 generations) of daily selection for large size, snowflake clusters evolve to increase their radius 1.7-fold by reducing the accumulation of internal stress. During this period, cells within the clusters evolve to be more elongated, concomitant with a decrease in the cellular volume fraction of the clusters. The associated increase in free space reduces the internal stress caused by cellular growth, thus delaying fracture and increasing cluster size. This work demonstrates how readily natural selection finds simple, physical solutions to spatial constraints that limit the evolution of group size-a fundamental step in the evolution of multicellularity.}, } @article {pmid35539534, year = {2018}, author = {Lee, DW and Kang, J and Hwang, HJ and Oh, MS and Shin, BC and Lee, MY and Kuh, HJ}, title = {Pitch-tunable pillar arrays for high-throughput culture and immunohistological analysis of tumor spheroids.}, journal = {RSC advances}, volume = {8}, number = {9}, pages = {4494-4502}, pmid = {35539534}, issn = {2046-2069}, abstract = {Tumor spheroids are multicellular, three-dimensional (3D) cell culture models closely mimicking the microenvironments of human tumors in vivo, thereby providing enhanced predictability, clinical relevancy of drug efficacy and the mechanism of action. Conventional confocal microscopic imaging remains inappropriate for immunohistological analysis due to current technical limits in immunostaining using antibodies and imaging cells grown in 3D multicellular contexts. Preparation of microsections of these spheroids represents a best alternative, yet their sub-millimeter size and fragility make it less practical for high-throughput screening. To address these problems, we developed a pitch-tunable 5 × 5 mini-pillar array chip for culturing and sectioning tumor spheroids in a high throughput manner. Tumor spheroids were 3D cultured in an alginate matrix using a twenty-five mini-pillar array which aligns to a 96-well. At least a few tens of spheroids per pillar were cultured and as many as 25 different treatment conditions per chip were evaluated, which indicated the high throughput manner of the 5 × 5 pillar array chip. The twenty-five mini-pillars were then rearranged to a transferring pitch so that spheroid-containing gel caps from all pillars can be embedded into a specimen block. Tissue array sections were then prepared and stained for immunohistological examination. The utility of this pitch-tunable pillar array was demonstrated by evaluating drug distribution and expression levels of several proteins following drug treatment in 3D tumor spheroids. Overall, our mini-pillar array provides a novel platform that can be useful for culturing tumor spheroids as well as for immunohistological analysis in a multiplexed and high throughput manner.}, } @article {pmid33365125, year = {2015}, author = {Coventry, BJ and Henneberg, M}, title = {The Immune System and Responses to Cancer: Coordinated Evolution.}, journal = {F1000Research}, volume = {4}, number = {}, pages = {552}, pmid = {33365125}, issn = {2046-1402}, abstract = {This review explores the incessant evolutionary interaction and co-development between immune system evolution and somatic evolution, to put it into context with the short, over 60-year, detailed human study of this extraordinary protective system. Over millions of years, the evolutionary development of the immune system in most species has been continuously shaped by environmental interactions between microbes, and aberrant somatic cells, including malignant cells. Not only has evolution occurred in somatic cells to adapt to environmental pressures for survival purposes, but the immune system and its function has been successively shaped by those same evolving somatic cells and microorganisms through continuous adaptive symbiotic processes of progressive simultaneous immunological and somatic change to provide what we observe today. Indeed, the immune system as an environmental influence has also shaped somatic and microbial evolution. Although the immune system is tuned to primarily controlling microbiological challenges for combatting infection, it can also remove damaged and aberrant cells, including cancer cells to induce long-term cures. Our knowledge of how this occurs is just emerging. Here we consider the connections between immunity, infection and cancer, by searching back in time hundreds of millions of years to when multi-cellular organisms first began. We are gradually appreciating that the immune system has evolved into a truly brilliant and efficient protective mechanism, the importance of which we are just beginning to now comprehend. Understanding these aspects will likely lead to more effective cancer and other therapies.}, } @article {pmid32262456, year = {2015}, author = {Rocha, PRF and Schlett, P and Schneider, L and Dröge, M and Mailänder, V and Gomes, HL and Blom, PWM and de Leeuw, DM}, title = {Low frequency electric current noise in glioma cell populations.}, journal = {Journal of materials chemistry. B}, volume = {3}, number = {25}, pages = {5035-5039}, doi = {10.1039/c5tb00144g}, pmid = {32262456}, issn = {2050-7518}, abstract = {Measuring the electrical activity of large and defined populations of cells is currently a major technical challenge to electrophysiology, especially in the picoampere-range. For this purpose, we developed and applied a bidirectional transducer based on a chip with interdigitated gold electrodes to record the electrical response of cultured glioma cells. Recent research determined that also non-neural brain glia cells are electrically active and excitable. Their transformed counterparts, e.g. glioma cells, were suggested to partially retain these electric features. Such electrophysiological studies however are usually performed on individual cells and are limited in their predictive power for the overall electrical activity of the multicellular tumour bulk. Our extremely low-noise measuring system allowed us to detect not only prominent electrical bursts of neuronal cells but also minute, yet constantly occurring and functional, membrane capacitive current oscillations across large populations of C6 glioma cells, which we termed electric current noise. At the same time, tumour cells of non-brain origin (HeLa) proved to be electrically quiescent in comparison. Finally, we determined that the glioma cell activity is primarily caused by the opening of voltage-gated Na[+] and K[+] ion channels and can be efficiently abolished using specific pharmacological inhibitors. Thus, we offer here a unique approach for studying electrophysiological properties of large cancer cell populations as an in vitro reference for tumour bulks in vivo.}, } @article {pmid32688947, year = {2004}, author = {Boyer, JS and Silk, WK}, title = {Hydraulics of plant growth.}, journal = {Functional plant biology : FPB}, volume = {31}, number = {8}, pages = {761-773}, doi = {10.1071/FP04062}, pmid = {32688947}, issn = {1445-4416}, abstract = {Multicellular plants rely on growth in localised regions that contain small, undifferentiated cells and may be many millimetres from the nearest differentiated xylem and phloem. Water and solutes must move to these small cells for their growth. Increasing evidence indicates that after exiting the xylem and phloem, water and solutes are driven to the growing cells by gradients in water potential and solute potential or concentration. The gradients are much steeper than in the vascular transport system and can change in magnitude or suffer local disruption with immediate consequences for growth. Their dynamics often obscure how turgor drives wall extension for growth, and different flow paths for roots and shoots have different dynamics. In this review, the origins of the gradients, their mode of action and their consequences are discussed, with emphasis on how their dynamics affect growth processes.}, } @article {pmid32050735, year = {2001}, author = {Puigderrajols, P and Mir, G and Molinas, M}, title = {Ultrastructure of Early Secondary Embryogenesis by Multicellular and Unicellular Pathways in Cork Oak (Quercus suber L.).}, journal = {Annals of botany}, volume = {87}, number = {2}, pages = {179-189}, doi = {10.1006/anbo.2000.1317}, pmid = {32050735}, issn = {1095-8290}, abstract = {Early cellular events during secondary embryogenesis were studied in a cork oak recurrent embryogenic system in which embryos arise either in a multicellular budding pathway from a compact mass of proliferation or from isolated single cells in friable callus. The compact mass of proliferation originated from the epidermal cells at the hypocotyl whose growth and convolution was characterized by a decrease in the nucleus/cytoplasm ratio and a marked increase in storage products. The transition from the compact mass to meristematic primordia occurred at the periphery and was accompanied by cell dedifferentiation and a drastic reduction of storage products. Meristematic primordia evolved to globular embryos by the organization of a protodermis and two internal centres. Microscope analysis of friable callus showed an hypothetical sequence from single cells to aggregates of a few cells, meristematic cell clusters and globular embryos. Single cells showed typical features of embryogenic cells such as rich cytoplasm and a large number of starch grains and lipid bodies. A progressive cell dedifferentiation and a drastic reduction of storage products was observed when aggregates of a few cells and meristematic cell clusters were compared. Progressive bipolarization in large meristematic cell clusters initiated globular embryo formation. The comparison of both embryogenic pathways at the ultrastructural level showed that subcellular changes follow a similar sequential pattern, especially with regard to the storage products. The possible role of plastid extrusions and multivesicular bodies in the changing pattern of starch metabolism during embryogenesis is discussed.}, } @article {pmid33874589, year = {1993}, author = {Lucas, WJ and Ding, B and VAN DER Schoot, C}, title = {Plasmodesmata and the supracellular nature of plants.}, journal = {The New phytologist}, volume = {125}, number = {3}, pages = {435-476}, doi = {10.1111/j.1469-8137.1993.tb03897.x}, pmid = {33874589}, issn = {1469-8137}, abstract = {In the classical formulation of Münch (1930), plasmodesmata are considered to form simple cytoplasmic bridges between neighbouring plant cells to create the symplasm. This concept has dominated, if not monopolized, the thinking of plant biologists and in particular plant physiologists over the last few decades. Recent advances in ultrastructural, physiological and molecular studies on plasmodesmata indicate that this simple view is in need of revision. Structurally, the higher plant plasmodesma has been revealed to be a supramolecular complex consisting of membranes and proteins. Functionally, evidence is at hand that this complex structure appears to have evolved not only to control the size exclusion limit for intercellular diffusion of metabolites and small molecules, but also to potentiate and regulate intercellular trafficking of macromolecules, including proteins and nucleic acids. In this regard, plasmodesmal transport may share parallel regulatory mechanisms with nucleocytoplasmic transport. Based on these findings, we advance the hypothesis that plants function as supracellular, rather than multicellular, organisms. As such, the dynamics of the plant body, including cell differentiation, tissue formation, organogenesis and specialized physiological function(s), is subject to plasmodesmal regulation. Plasmodesmata presumably accomplish such regulatory roles by trafficking informational molecules which orchestrate both metabolic activity and gene expression. Current and future studies on the evolutionary origin(s) of plasmodesmata are likely to provide valuable information in terms of the genetic and molecular basis for the supracellular nature of plants. Contents Summary 435 I. Introduction 436 II. Plasmodesmal formation, structure and biochemistry 436 III. Evolution of plasmodesmata 445 IV. Symplasmic dynamics 452 V. Plasniodesmal trafficking of macromolecules: parallels with nucleocytoplasmic transport 457 VI. Role of plasmodesmata in plant development 464 VII. Concluding remarks 469 Acknowledgements 470 References 470.}, } @article {pmid31601898, year = {2019}, author = {Agić, H and Högström, AES and Moczydłowska, M and Jensen, S and Palacios, T and Meinhold, G and Ebbestad, JOR and Taylor, WL and Høyberget, M}, title = {Organically-preserved multicellular eukaryote from the early Ediacaran Nyborg Formation, Arctic Norway.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {14659}, pmid = {31601898}, issn = {2045-2322}, mesh = {Aquatic Organisms/cytology/*ultrastructure ; Arctic Regions ; *Biological Evolution ; Eukaryota/cytology/*ultrastructure ; Fossils/*ultrastructure ; Microscopy, Electrochemical, Scanning ; Norway ; }, abstract = {Eukaryotic multicellularity originated in the Mesoproterozoic Era and evolved multiple times since, yet early multicellular fossils are scarce until the terminal Neoproterozoic and often restricted to cases of exceptional preservation. Here we describe unusual organically-preserved fossils from mudrocks, that provide support for the presence of organisms with differentiated cells (potentially an epithelial layer) in the late Neoproterozoic. Cyathinema digermulense gen. et sp. nov. from the Nyborg Formation, Vestertana Group, Digermulen Peninsula in Arctic Norway, is a new carbonaceous organ-taxon which consists of stacked tubes with cup-shaped ends. It represents parts of a larger organism (multicellular eukaryote or a colony), likely with greater preservation potential than its other elements. Arrangement of open-ended tubes invites comparison with cells of an epithelial layer present in a variety of eukaryotic clades. This tissue may have benefitted the organism in: avoiding overgrowth, limiting fouling, reproduction, or water filtration. C. digermulense shares characteristics with extant and fossil groups including red algae and their fossils, demosponge larvae and putative sponge fossils, colonial protists, and nematophytes. Regardless of its precise affinity, C. digermulense was a complex and likely benthic marine eukaryote exhibiting cellular differentiation, and a rare occurrence of early multicellularity outside of Konservat-Lagerstätten.}, } @article {pmid31597590, year = {2020}, author = {Diggle, SP and Whiteley, M}, title = {Microbe Profile: Pseudomonas aeruginosa: opportunistic pathogen and lab rat.}, journal = {Microbiology (Reading, England)}, volume = {166}, number = {1}, pages = {30-33}, pmid = {31597590}, issn = {1465-2080}, support = {R01 GM116547/GM/NIGMS NIH HHS/United States ; R56 HL142857/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Biofilms/growth & development ; Biological Evolution ; Drug Resistance, Bacterial ; Genome, Bacterial/genetics ; Humans ; Phylogeny ; Pseudomonas Infections/*microbiology ; Pseudomonas aeruginosa/classification/genetics/*pathogenicity/*physiology ; Virulence ; }, abstract = {Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen and a model bacterium for studying virulence and bacterial social traits. While it can be isolated in low numbers from a wide variety of environments including soil and water, it can readily be found in almost any human/animal-impacted environment. It is a major cause of illness and death in humans with immunosuppressive and chronic conditions, and infections in these patients are difficult to treat due to a number of antibiotic resistance mechanisms and the organism's propensity to form multicellular biofilms.}, } @article {pmid31589468, year = {2019}, author = {Blutt, SE and Klein, OD and Donowitz, M and Shroyer, N and Guha, C and Estes, MK}, title = {Use of organoids to study regenerative responses to intestinal damage.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {317}, number = {6}, pages = {G845-G852}, pmid = {31589468}, issn = {1522-1547}, support = {R24 DK099803/DK/NIDDK NIH HHS/United States ; U01 DK103117/DK/NIDDK NIH HHS/United States ; P30 DK089502/DK/NIDDK NIH HHS/United States ; U24 DK085532/DK/NIDDK NIH HHS/United States ; R01 DK118904/DK/NIDDK NIH HHS/United States ; U19 AI116497/AI/NIAID NIH HHS/United States ; U01 DK085532/DK/NIDDK NIH HHS/United States ; U01 DK103168/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; }, mesh = {*Adult Stem Cells ; Animals ; Cells, Cultured/physiology/transplantation ; Humans ; *Intestinal Diseases/etiology/metabolism/therapy ; *Intestines/drug effects/radiation effects ; Models, Biological ; *Organoids/physiology/transplantation ; Regeneration/*physiology ; Tissue Engineering/methods ; }, abstract = {Intestinal organoid cultures provide an in vitro model system for studying pathways and mechanisms involved in epithelial damage and repair. Derived from either embryonic or induced pluripotent stem cells or adult intestinal stem cells or tissues, these self-organizing, multicellular structures contain polarized mature cells that recapitulate both the physiology and heterogeneity of the intestinal epithelium. These cultures provide a cutting-edge technology for defining regenerative pathways that are induced following radiation or chemical damage, which directly target the cycling intestinal stem cell, or damage resulting from viral, bacterial, or parasitic infection of the epithelium. Novel signaling pathways or biological mechanisms identified from organoid studies that mediate regeneration of the epithelium following damage are likely to be important targets of preventive or therapeutic modalities to mitigate intestinal injury. The evolution of these cultures to include more components of the intestinal wall and the ability to genetically modify them are key components for defining the mechanisms that modulate epithelial regeneration.}, } @article {pmid31589243, year = {2020}, author = {Arcas, A and Wilkinson, DG and Nieto, MÁ}, title = {The Evolutionary History of Ephs and Ephrins: Toward Multicellular Organisms.}, journal = {Molecular biology and evolution}, volume = {37}, number = {2}, pages = {379-394}, pmid = {31589243}, issn = {1537-1719}, support = {/WT_/Wellcome Trust/United Kingdom ; FC001217/CRUK_/Cancer Research UK/United Kingdom ; FC001217/MRC_/Medical Research Council/United Kingdom ; FC001217/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Communication ; Choanoflagellata/genetics/metabolism ; Ephrins/*genetics/*metabolism ; Evolution, Molecular ; Humans ; Phylogeny ; Porifera/genetics/metabolism ; Receptors, Eph Family/*genetics/*metabolism ; Signal Transduction ; Vertebrates/genetics/metabolism ; }, abstract = {Eph receptor (Eph) and ephrin signaling regulate fundamental developmental processes through both forward and reverse signaling triggered upon cell-cell contact. In vertebrates, they are both classified into classes A and B, and some representatives have been identified in many metazoan groups, where their expression and functions have been well studied. We have extended previous phylogenetic analyses and examined the presence of Eph and ephrins in the tree of life to determine their origin and evolution. We have found that 1) premetazoan choanoflagellates may already have rudimental Eph/ephrin signaling as they have an Eph-/ephrin-like pair and homologs of downstream-signaling genes; 2) both forward- and reverse-downstream signaling might already occur in Porifera since sponges have most genes involved in these types of signaling; 3) the nonvertebrate metazoan Eph is a type-B receptor that can bind ephrins regardless of their membrane-anchoring structure, glycosylphosphatidylinositol, or transmembrane; 4) Eph/ephrin cross-class binding is specific to Gnathostomata; and 5) kinase-dead Eph receptors can be traced back to Gnathostomata. We conclude that Eph/ephrin signaling is of older origin than previously believed. We also examined the presence of protein domains associated with functional characteristics and the appearance and conservation of downstream-signaling pathways to understand the original and derived functions of Ephs and ephrins. We find that the evolutionary history of these gene families points to an ancestral function in cell-cell interactions that could contribute to the emergence of multicellularity and, in particular, to the required segregation of cell populations.}, } @article {pmid31587642, year = {2019}, author = {López-Escardó, D and Grau-Bové, X and Guillaumet-Adkins, A and Gut, M and Sieracki, ME and Ruiz-Trillo, I}, title = {Reconstruction of protein domain evolution using single-cell amplified genomes of uncultured choanoflagellates sheds light on the origin of animals.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1786}, pages = {20190088}, pmid = {31587642}, issn = {1471-2970}, mesh = {Choanoflagellata/*genetics ; *Evolution, Molecular ; *Genome, Protozoan ; Protein Domains/*genetics ; }, abstract = {Understanding the origins of animal multicellularity is a fundamental biological question. Recent genome data have unravelled the role that co-option of pre-existing genes played in the origin of animals. However, there were also some important genetic novelties at the onset of Metazoa. To have a clear understanding of the specific genetic innovations and how they appeared, we need the broadest taxon sampling possible, especially among early-branching animals and their unicellular relatives. Here, we take advantage of single-cell genomics to expand our understanding of the genomic diversity of choanoflagellates, the sister-group to animals. With these genomes, we have performed an updated and taxon-rich reconstruction of protein evolution from the Last Eukaryotic Common Ancestor (LECA) to animals. Our novel data re-defines the origin of some genes previously thought to be metazoan-specific, like the POU transcription factor, which we show appeared earlier in evolution. Moreover, our data indicate that the acquisition of new genes at the stem of Metazoa was mainly driven by duplications and protein domain rearrangement processes at the stem of Metazoa. Furthermore, our analysis allowed us to reveal protein domains that are essential to the maintenance of animal multicellularity. Our analyses also demonstrate the utility of single-cell genomics from uncultured taxa to address evolutionary questions. This article is part of a discussion meeting issue 'Single cell ecology'.}, } @article {pmid31584936, year = {2019}, author = {Chang, J and Xu, Z and Li, M and Yang, M and Qin, H and Yang, J and Wu, S}, title = {Spatiotemporal cytoskeleton organizations determine morphogenesis of multicellular trichomes in tomato.}, journal = {PLoS genetics}, volume = {15}, number = {10}, pages = {e1008438}, pmid = {31584936}, issn = {1553-7404}, mesh = {Actin Cytoskeleton/genetics/metabolism ; Actin-Related Protein 2-3 Complex/genetics/metabolism ; Solanum lycopersicum/genetics/*growth & development/metabolism ; Microfilament Proteins/*genetics/metabolism ; Microtubules/genetics/metabolism ; *Morphogenesis ; Mutation ; Plant Proteins/*genetics/metabolism ; Spatio-Temporal Analysis ; Trichomes/genetics/*growth & development ; }, abstract = {Plant trichomes originate from epidermal cell, forming protective structure from abiotic and biotic stresses. Different from the unicellular trichome in Arabidopsis, tomato trichomes are multicellular structure and can be classified into seven different types based on cell number, shape and the presence of glandular cells. Despite the importance of tomato trichomes in insect resistance, our understanding of the tomato trichome morphogenesis remains elusive. In this study, we quantitatively analyzed morphological traits of trichomes in tomato and further performed live imaging of cytoskeletons in stably transformed lines with actin and microtubule markers. At different developmental stages, two types of cytoskeletons exhibited distinct patterns in different trichome cells, ranging from transverse, spiral to longitudinal. This gradual transition of actin filament angle from basal to top cells could correlate with the spatial expansion mode in different cells. Further genetic screen for aberrant trichome morphology led to the discovery of a number of independent mutations in SCAR/WAVE and ARP2/3 complex, which resulted in actin bundling and distorted trichomes. Disruption of microtubules caused isotropic expansion while abolished actin filaments entirely inhibited axial extension of trichomes, indicating that microtubules and actin filaments may control distinct aspects of trichome cell expansion. Our results shed light on the roles of cytoskeletons in the formation of multicellular structure of tomato trichomes.}, } @article {pmid31581262, year = {2019}, author = {Garud, A and Carrillo, AJ and Collier, LA and Ghosh, A and Kim, JD and Lopez-Lopez, B and Ouyang, S and Borkovich, KA}, title = {Genetic relationships between the RACK1 homolog cpc-2 and heterotrimeric G protein subunit genes in Neurospora crassa.}, journal = {PloS one}, volume = {14}, number = {10}, pages = {e0223334}, pmid = {31581262}, issn = {1932-6203}, support = {P01 GM068087/GM/NIGMS NIH HHS/United States ; R01 GM086565/GM/NIGMS NIH HHS/United States ; T34 GM062756/GM/NIGMS NIH HHS/United States ; }, mesh = {Genes, Fungal ; Heterotrimeric GTP-Binding Proteins/chemistry/*genetics/metabolism ; Models, Biological ; Mutation ; Neurospora crassa/classification/*genetics/immunology ; Phenotype ; Phylogeny ; Protein Binding ; Recombinant Proteins ; rho-Associated Kinases/chemistry/*genetics/metabolism ; }, abstract = {Receptor for Activated C Kinase-1 (RACK1) is a multifunctional eukaryotic scaffolding protein with a seven WD repeat structure. Among their many cellular roles, RACK1 homologs have been shown to serve as alternative Gβ subunits during heterotrimeric G protein signaling in many systems. We investigated genetic interactions between the RACK1 homolog cpc-2, the previously characterized Gβ subunit gnb-1 and other G protein signaling components in the multicellular filamentous fungus Neurospora crassa. Results from cell fractionation studies and from fluorescent microscopy of a strain expressing a CPC-2-GFP fusion protein revealed that CPC-2 is a cytoplasmic protein. Genetic epistasis experiments between cpc-2, the three Gα genes (gna-1, gna-2 and gna-3) and gnb-1 demonstrated that cpc-2 is epistatic to gna-2 with regards to basal hyphae growth rate and aerial hyphae height, while deletion of cpc-2 mitigates the increased macroconidiation on solid medium observed in Δgnb-1 mutants. Δcpc-2 mutants inappropriately produce conidiophores during growth in submerged culture and mutational activation of gna-3 alleviates this defect. Δcpc-2 mutants are female-sterile and fertility could not be restored by mutational activation of any of the three Gα genes. With the exception of macroconidiation on solid medium, double mutants lacking cpc-2 and gnb-1 exhibited more severe defects for all phenotypic traits, supporting a largely synergistic relationship between GNB-1 and CPC-2 in N. crassa.}, } @article {pmid31569378, year = {2019}, author = {Zárybnický, T and Matoušková, P and Ambrož, M and Šubrt, Z and Skálová, L and Boušová, I}, title = {The Selection and Validation of Reference Genes for mRNA and microRNA Expression Studies in Human Liver Slices Using RT-qPCR.}, journal = {Genes}, volume = {10}, number = {10}, pages = {}, pmid = {31569378}, issn = {2073-4425}, mesh = {14-3-3 Proteins/genetics/metabolism ; Adult ; Aged ; Cytochrome P-450 CYP1A2/genetics/metabolism ; Cytochrome P-450 CYP3A/genetics/metabolism ; Cytochrome P-450 Enzyme System/pharmacology ; Dimethyl Sulfoxide/pharmacology ; Female ; Gene Expression Profiling/*standards ; Humans ; Liver/drug effects/*metabolism ; Male ; MicroRNAs/*genetics/metabolism ; Middle Aged ; RNA, Messenger/*genetics/metabolism ; Real-Time Polymerase Chain Reaction/*standards ; Reference Standards ; Rifampin/pharmacology ; Transcriptome ; beta 2-Microglobulin/genetics/metabolism ; beta-Naphthoflavone/pharmacology ; }, abstract = {The selection of a suitable combination of reference genes (RGs) for data normalization is a crucial step for obtaining reliable and reproducible results from transcriptional response analysis using a reverse transcription-quantitative polymerase chain reaction. This is especially so if a three-dimensional multicellular model prepared from liver tissues originating from biologically diverse human individuals is used. The mRNA and miRNA RGs stability were studied in thirty-five human liver tissue samples and twelve precision-cut human liver slices (PCLS) treated for 24 h with dimethyl sulfoxide (controls) and PCLS treated with β-naphthoflavone (10 µM) or rifampicin (10 µM) as cytochrome P450 (CYP) inducers. Validation of RGs was performed by an expression analysis of CYP3A4 and CYP1A2 on rifampicin and β-naphthoflavone induction, respectively. Regarding mRNA, the best combination of RGs for the controls was YWHAZ and B2M, while YWHAZ and ACTB were selected for the liver samples and treated PCLS. Stability of all candidate miRNA RGs was comparable or better than that of generally used short non-coding RNA U6. The best combination for the control PCLS was miR-16-5p and miR-152-3p, in contrast to the miR-16-5b and miR-23b-3p selected for the treated PCLS. Our results showed that the candidate RGs were rather stable, especially for miRNA in human PCLS.}, } @article {pmid31568885, year = {2019}, author = {Thakur, R and Shiratori, T and Ishida, KI}, title = {Taxon-rich Multigene Phylogenetic Analyses Resolve the Phylogenetic Relationship Among Deep-branching Stramenopiles.}, journal = {Protist}, volume = {170}, number = {5}, pages = {125682}, doi = {10.1016/j.protis.2019.125682}, pmid = {31568885}, issn = {1618-0941}, mesh = {*Phylogeny ; Stramenopiles/*classification/*genetics ; Transcriptome ; }, abstract = {Stramenopiles are one of the major eukaryotic assemblages. This group comprises a wide range of species including photosynthetic unicellular and multicellular algae, fungus-like osmotrophic organisms and many free-living phagotrophic flagellates. However, the phylogeny of the Stramenopiles, especially relationships among deep-branching heterotrophs, has not yet been resolved because of a lack of adequate transcriptomic data for representative lineages. In this study, we performed multigene phylogenetic analyses of deep-branching Stramenopiles with improved taxon sampling. We sequenced transcriptomes of three deep-branching Stramenopiles: Incisomonas marina, Pseudophyllomitus vesiculosus and Platysulcus tardus. Phylogenetic analyses using 120 protein-coding genes and 56 taxa indicated that Pl. tardus is sister to all other Stramenopiles while Ps. vesiculosus is sister to MAST-4 and form a robust clade with the Labyrinthulea. The resolved phylogenetic relationships of deep-branching Stramenopiles provide insights into the ancestral traits of the Stramenopiles.}, } @article {pmid31568790, year = {2020}, author = {Newman, SA}, title = {Cell differentiation: What have we learned in 50 years?.}, journal = {Journal of theoretical biology}, volume = {485}, number = {}, pages = {110031}, doi = {10.1016/j.jtbi.2019.110031}, pmid = {31568790}, issn = {1095-8541}, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation/genetics ; Eukaryota/genetics ; Evolution, Molecular ; Gene Expression Regulation ; *Gene Regulatory Networks ; }, abstract = {I revisit two theories of cell differentiation in multicellular organisms published a half-century ago, Stuart Kauffman's global genome regulatory dynamics (GGRD) model and Roy Britten's and Eric Davidson's modular gene regulatory network (MGRN) model, in light of newer knowledge of mechanisms of gene regulation in the metazoans (animals). The two models continue to inform hypotheses and computational studies of differentiation of lineage-adjacent cell types. However, their shared notion (based on bacterial regulatory systems) of gene switches and networks built from them have constrained progress in understanding the dynamics and evolution of differentiation. Recent work has described unique write-read-rewrite chromatin-based expression encoding in eukaryotes, as well metazoan-specific processes of gene activation and silencing in condensed-phase, enhancer-recruiting regulatory hubs, employing disordered proteins, including transcription factors, with context-dependent identities. These findings suggest an evolutionary scenario in which the origination of differentiation in animals, rather than depending exclusively on adaptive natural selection, emerged as a consequence of a type of multicellularity in which the novel metazoan gene regulatory apparatus was readily mobilized to amplify and exaggerate inherent cell functions of unicellular ancestors. The plausibility of this hypothesis is illustrated by the evolution of the developmental role of Grainyhead-like in the formation of epithelium.}, } @article {pmid31565856, year = {2019}, author = {Gilbert, SF}, title = {Evolutionary transitions revisited: Holobiont evo-devo.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {8}, pages = {307-314}, doi = {10.1002/jez.b.22903}, pmid = {31565856}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; *Developmental Biology ; Host Microbial Interactions ; Life Cycle Stages ; Microbiota ; *Symbiosis ; }, abstract = {John T. Bonner lists four essential transformations in the evolution of life: the emergence of the eukaryotic cell, meiosis, multicellularity, and the nervous system. This paper analyses the mechanisms for those transitions in light of three of Dr. Bonner's earlier hypotheses: (a) that the organism is its life cycle, (b) that evolution consists of alterations of the life cycle, and (c) that development extends beyond the body and into interactions with other organisms. Using the notion of the holobiont life cycle, this paper attempts to show that these evolutionary transitions can be accomplished through various means of symbiosis. Perceiving the organism both as an interspecies consortium and as a life cycle supports a twofold redefinition of the organism as a holobiont constructed by integrating together the life cycles of several species. These findings highlight the importance of symbiosis and the holobiont development in analyses of evolution.}, } @article {pmid31563945, year = {2020}, author = {Hernández-Hernández, V and Benítez, M and Boudaoud, A}, title = {Interplay between turgor pressure and plasmodesmata during plant development.}, journal = {Journal of experimental botany}, volume = {71}, number = {3}, pages = {768-777}, doi = {10.1093/jxb/erz434}, pmid = {31563945}, issn = {1460-2431}, mesh = {Hydrostatic Pressure ; *Osmotic Pressure ; Permeability ; *Plant Development ; Plasmodesmata/*physiology ; }, abstract = {Plasmodesmata traverse cell walls, generating connections between neighboring cells. They allow intercellular movement of molecules such as transcription factors, hormones, and sugars, and thus create a symplasmic continuity within a tissue. One important factor that determines plasmodesmal permeability is their aperture, which is regulated during developmental and physiological processes. Regulation of aperture has been shown to affect developmental events such as vascular differentiation in the root, initiation of lateral roots, or transition to flowering. Extensive research has unraveled molecular factors involved in the regulation of plasmodesmal permeability. Nevertheless, many plant developmental processes appear to involve feedbacks mediated by mechanical forces, raising the question of whether mechanical forces and plasmodesmal permeability affect each other. Here, we review experimental data on how one of these forces, turgor pressure, and plasmodesmal permeability may mutually influence each other during plant development, and we discuss the questions raised by these data. Addressing such questions will improve our knowledge of how cellular patterns emerge during development, shedding light on the evolution of complex multicellular plants.}, } @article {pmid31552662, year = {2020}, author = {Wanninger, A and Wollesen, T}, title = {Methods in Brain Development of Molluscs.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2047}, number = {}, pages = {311-324}, doi = {10.1007/978-1-4939-9732-9_17}, pmid = {31552662}, issn = {1940-6029}, mesh = {Animals ; Brain/growth & development/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Immunohistochemistry/*methods ; In Situ Hybridization/*methods ; Microscopy, Confocal ; Mollusca/*growth & development/metabolism ; }, abstract = {Representatives of the phylum Mollusca have long been important models in neurobiological research. Recently, the routine application of immunocytochemistry and gene expression analyses in combination with confocal laserscanning microscopy has allowed fast generation of highly detailed reconstructions of neural structures of even the smallest multicellular animals, including early developmental stages. As a consequence, large-scale comparative analyses of neurogenesis-an important prerequisite for inferences concerning the evolution of animal nervous systems-are now possible in a reasonable amount of time. Herein, we describe immunocytochemical staining and in situ hybridization protocols for both, whole-mount preparations of developmental stages-usually 70-300 μm in size-as well as for vibratome and cryostat sections of complex brains. Although our procedures have been optimized for marine molluscs, they may easily be adapted to other (marine) organisms by the creative neurobiologist.}, } @article {pmid31542284, year = {2019}, author = {Barger, SR and James, ML and Pellenz, CD and Krendel, M and Sirotkin, V}, title = {Human myosin 1e tail but not motor domain replaces fission yeast Myo1 domains to support myosin-I function during endocytosis.}, journal = {Experimental cell research}, volume = {384}, number = {2}, pages = {111625}, pmid = {31542284}, issn = {1090-2422}, support = {R01 DK083345/DK/NIDDK NIH HHS/United States ; }, mesh = {Actins/metabolism ; Endocytosis/*physiology ; Humans ; Myosin Heavy Chains/*metabolism ; Myosin Type I/*metabolism ; Protein Domains/physiology ; Schizosaccharomyces/*metabolism ; Schizosaccharomyces pombe Proteins/*metabolism ; }, abstract = {In both unicellular and multicellular organisms, long-tailed class I myosins function in clathrin-mediated endocytosis. Myosin 1e (Myo1e) in vertebrates and Myo1 in fission yeast have similar domain organization, yet whether these proteins or their individual protein domains are functionally interchangeable remains unknown. In an effort to assess functional conservation of class I myosins, we tested whether human Myo1e could replace Myo1 in fission yeast Schizosaccharomyces pombe and found that it was unable to substitute for yeast Myo1. To determine if any individual protein domain is responsible for the inability of Myo1e to function in yeast, we created human-yeast myosin-I chimeras. By functionally testing these chimeric myosins in vivo, we concluded that the Myo1e motor domain is unable to function in yeast, even when combined with the yeast Myo1 tail and a full complement of yeast regulatory light chains. Conversely, the Myo1e tail, when attached to the yeast Myo1 motor domain, supports localization to endocytic actin patches and partially rescues the endocytosis defect in myo1Δ cells. Further dissection showed that both the TH1 and TH2-SH3 domains in the human Myo1e tail are required for localization and function of chimeric myosin-I at endocytic sites. Overall, this study provides insights into the role of individual myosin-I domains, expands the utility of fission yeast as a simple model system to study the effects of disease-associated MYO1E mutations, and supports a model of co-evolution between a myosin motor and its actin track.}, } @article {pmid31540916, year = {2019}, author = {Pukhlyakova, EA and Kirillova, AO and Kraus, YA and Zimmermann, B and Technau, U}, title = {A cadherin switch marks germ layer formation in the diploblastic sea anemone Nematostella vectensis.}, journal = {Development (Cambridge, England)}, volume = {146}, number = {20}, pages = {}, doi = {10.1242/dev.174623}, pmid = {31540916}, issn = {1477-9129}, mesh = {Animals ; Cadherins/*metabolism ; Ectoderm/cytology/metabolism ; Embryo, Nonmammalian/*cytology/*metabolism ; Endoderm/cytology/metabolism ; Germ Layers/*cytology/*metabolism ; Sea Anemones/*embryology/*metabolism ; }, abstract = {Morphogenesis is a shape-building process during development of multicellular organisms. During this process, the establishment and modulation of cell-cell contacts play an important role. Cadherins, the major cell adhesion molecules, form adherens junctions connecting epithelial cells. Numerous studies of Bilateria have shown that cadherins are associated with the regulation of cell differentiation, cell shape changes, cell migration and tissue morphogenesis. To date, the role of cadherins in non-bilaterians is unknown. Here, we study the expression and function of two paralogous classical cadherins, Cadherin 1 and Cadherin 3, in a diploblastic animal, the sea anemone Nematostella vectensis We show that a cadherin switch accompanies the formation of germ layers. Using specific antibodies, we show that both cadherins are localized to adherens junctions at apical and basal positions in ectoderm and endoderm. During gastrulation, partial epithelial-to-mesenchymal transition of endodermal cells is marked by stepwise downregulation of Cadherin 3 and upregulation of Cadherin 1. Knockdown experiments show that both cadherins are required for maintenance of tissue integrity and tissue morphogenesis. Thus, both sea anemones and bilaterians use independently duplicated cadherins combinatorially for tissue morphogenesis and germ layer differentiation.}, } @article {pmid31540472, year = {2019}, author = {Denes, V and Geck, P and Mester, A and Gabriel, R}, title = {Pituitary Adenylate Cyclase-Activating Polypeptide: 30 Years in Research Spotlight and 600 Million Years in Service.}, journal = {Journal of clinical medicine}, volume = {8}, number = {9}, pages = {}, pmid = {31540472}, issn = {2077-0383}, abstract = {Emerging from the depths of evolution, pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors (i.e., PAC1, VPAC1, VPAC2) are present in multicellular organisms from Tunicates to humans and govern a remarkable number of physiological processes. Consequently, the clinical relevance of PACAP systems spans a multifaceted palette that includes more than 40 disorders. We aimed to present the versatility of PACAP1-38 actions with a focus on three aspects: (1) when PACAP1-38 could be a cause of a malfunction, (2) when PACAP1-38 could be the cure for a malfunction, and (3) when PACAP1-38 could either improve or impair biology. PACAP1-38 is implicated in the pathophysiology of migraine and post-traumatic stress disorder whereas an outstanding protective potential has been established in ischemia and in Alzheimer's disease. Lastly, PACAP receptors could mediate opposing effects both in cancers and in inflammation. In the light of the above, the duration and concentrations of PACAP agents must be carefully set at any application to avoid unwanted consequences. An enormous amount of data accumulated since its discovery (1989) and the first clinical trials are dated in 2017. Thus in the field of PACAP research: "this is not the end, not even the beginning of the end, but maybe the end of the beginning."}, } @article {pmid31534207, year = {2019}, author = {Moger-Reischer, RZ and Lennon, JT}, title = {Microbial ageing and longevity.}, journal = {Nature reviews. Microbiology}, volume = {17}, number = {11}, pages = {679-690}, doi = {10.1038/s41579-019-0253-y}, pmid = {31534207}, issn = {1740-1534}, mesh = {Adaptation, Physiological ; Environmental Exposure ; *Homeostasis ; *Metabolism ; *Microbial Viability ; Models, Biological ; }, abstract = {Longevity reflects the ability to maintain homeostatic conditions necessary for life as an organism ages. A long-lived organism must contend not only with environmental hazards but also with internal entropy and macromolecular damage that result in the loss of fitness during ageing, a phenomenon known as senescence. Although central to many of the core concepts in biology, ageing and longevity have primarily been investigated in sexually reproducing, multicellular organisms. However, growing evidence suggests that microorganisms undergo senescence, and can also exhibit extreme longevity. In this Review, we integrate theoretical and empirical insights to establish a unified perspective on senescence and longevity. We discuss the evolutionary origins, genetic mechanisms and functional consequences of microbial ageing. In addition to having biomedical implications, insights into microbial ageing shed light on the role of ageing in the origin of life and the upper limits to longevity.}, } @article {pmid31532063, year = {2019}, author = {Powell, R and O'Malley, MA}, title = {Metabolic and microbial perspectives on the "evolution of evolution".}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {8}, pages = {321-330}, doi = {10.1002/jez.b.22898}, pmid = {31532063}, issn = {1552-5015}, mesh = {*Biological Evolution ; *Metabolism ; *Microbiological Phenomena ; }, abstract = {Identifying and theorizing major turning points in the history of life generates insights into not only world-changing evolutionary events but also the processes that bring these events about. In his treatment of these issues, Bonner identifies the evolution of sex, multicellularity, and nervous systems as enabling the "evolution of evolution," which involves fundamental transformations in how evolution occurs. By contextualizing his framework within two decades of theorizing about major transitions in evolution, we identify some basic problems that Bonner's theory shares with much of the prevailing literature. These problems include implicit progressivism, theoretical disunity, and a limited ability to explain major evolutionary transformations. We go on to identify events and processes that are neglected by existing views. In contrast with the "vertical" focus on replication, hierarchy, and morphology that preoccupies most of the literature on major transitions, we propose a "horizontal" dimension in which metabolism and microbial innovations play a central explanatory role in understanding the broad-scale organization of life.}, } @article {pmid31529373, year = {2021}, author = {Erwin, DH}, title = {Tempos and modes of collectivity in the history of life.}, journal = {Theory in biosciences = Theorie in den Biowissenschaften}, volume = {140}, number = {4}, pages = {343-351}, pmid = {31529373}, issn = {1611-7530}, support = {NNA13AA90A//NASA Astrobiology Institute/ ; }, mesh = {Animals ; *Biological Evolution ; *Insecta ; Phylogeny ; }, abstract = {Collective integration and processing of information have increased through the history of life, through both the formation of aggregates in which the entities may have very different properties and which jointly coarse-grained environmental variables (ranging from widely varying metabolism in microbial consortia to the ecological diversity of species on reefs) and through collectives of similar entities (such as cells within an organism or social groups). Such increases have been implicated in significant transitions in the history of life, including aspects of the origin of life, the generation of pangenomes among microbes and microbial communities such as stromatolites, multicellularity and social insects. This contribution provides a preliminary overview of the dominant modes of collective information processing in the history of life, their phylogenetic distribution and extent of convergence, and the effects of new modes for integrating and acting upon information on the tempo of evolutionary change.}, } @article {pmid31521503, year = {2019}, author = {Kieninger, AK and Forchhammer, K and Maldener, I}, title = {A nanopore array in the septal peptidoglycan hosts gated septal junctions for cell-cell communication in multicellular cyanobacteria.}, journal = {International journal of medical microbiology : IJMM}, volume = {309}, number = {8}, pages = {151303}, doi = {10.1016/j.ijmm.2019.03.007}, pmid = {31521503}, issn = {1618-0607}, mesh = {Amidohydrolases/metabolism ; Anabaena/*cytology/enzymology ; *Cell Communication ; Gene Expression Regulation, Bacterial ; *Nanopores ; Nostoc/*cytology/enzymology ; Peptidoglycan/*metabolism ; Tight Junctions/metabolism ; }, abstract = {Some filamentous cyanobacteria are phototrophic bacteria with a true multicellular life style. They show patterned cell differentiation with the distribution of metabolic tasks between different cell types. This life style requires a system of cell-cell communication and metabolite exchange along the filament. During our study of the cell wall of species Nostoc punctiforme and Anabaena sp. PCC 7120 we discovered regular perforations in the septum between neighboring cells, which we called nanopore array. AmiC-like amidases are drilling the nanopores with a diameter of 20 nm, and are essential for communication and cell differentiation. NlpD-like regulators of AmiC activity and septum localized proteins SepJ, FraC and FraD are also involved in correct nanopore formation. By focused ion beam (FIB) milling and electron cryotomography we could visualize the septal junctions, which connect adjacent cells and pass thru the nanopores. They consist of cytoplasmic caps, which are missing in the fraD mutant, a plug inside the cytoplasmic membrane and a tube like conduit. A destroyed membrane potential and other stress factors lead to a conformational change in the cap structure and loss of cell-cell communication. These gated septal junctions of cyanobacteria are ancient structures that represent an example of convergent evolution, predating metazoan gap junctions.}, } @article {pmid31521200, year = {2019}, author = {Rausch, P and Rühlemann, M and Hermes, BM and Doms, S and Dagan, T and Dierking, K and Domin, H and Fraune, S and von Frieling, J and Hentschel, U and Heinsen, FA and Höppner, M and Jahn, MT and Jaspers, C and Kissoyan, KAB and Langfeldt, D and Rehman, A and Reusch, TBH and Roeder, T and Schmitz, RA and Schulenburg, H and Soluch, R and Sommer, F and Stukenbrock, E and Weiland-Bräuer, N and Rosenstiel, P and Franke, A and Bosch, T and Baines, JF}, title = {Comparative analysis of amplicon and metagenomic sequencing methods reveals key features in the evolution of animal metaorganisms.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {133}, pmid = {31521200}, issn = {2049-2618}, mesh = {Animals ; Bacteria/classification/genetics ; Databases, Genetic ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenome/genetics/*physiology ; Microbiota/genetics/*physiology ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {BACKGROUND: The interplay between hosts and their associated microbiome is now recognized as a fundamental basis of the ecology, evolution, and development of both players. These interdependencies inspired a new view of multicellular organisms as "metaorganisms." The goal of the Collaborative Research Center "Origin and Function of Metaorganisms" is to understand why and how microbial communities form long-term associations with hosts from diverse taxonomic groups, ranging from sponges to humans in addition to plants.

METHODS: In order to optimize the choice of analysis procedures, which may differ according to the host organism and question at hand, we systematically compared the two main technical approaches for profiling microbial communities, 16S rRNA gene amplicon and metagenomic shotgun sequencing across our panel of ten host taxa. This includes two commonly used 16S rRNA gene regions and two amplification procedures, thus totaling five different microbial profiles per host sample.

CONCLUSION: While 16S rRNA gene-based analyses are subject to much skepticism, we demonstrate that many aspects of bacterial community characterization are consistent across methods. The resulting insight facilitates the selection of appropriate methods across a wide range of host taxa. Overall, we recommend single- over multi-step amplification procedures, and although exceptions and trade-offs exist, the V3 V4 over the V1 V2 region of the 16S rRNA gene. Finally, by contrasting taxonomic and functional profiles and performing phylogenetic analysis, we provide important and novel insight into broad evolutionary patterns among metaorganisms, whereby the transition of animals from an aquatic to a terrestrial habitat marks a major event in the evolution of host-associated microbial composition.}, } @article {pmid31517991, year = {2020}, author = {de Araújo Silva-Cardoso, IM and Meira, FS and Gomes, ACMM and Scherwinski-Pereira, JE}, title = {Histology, histochemistry and ultrastructure of pre-embryogenic cells determined for direct somatic embryogenesis in the palm tree Syagrus oleracea.}, journal = {Physiologia plantarum}, volume = {168}, number = {4}, pages = {845-875}, doi = {10.1111/ppl.13026}, pmid = {31517991}, issn = {1399-3054}, support = {426637/2016-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 001-2011/Grant 39//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 01.08.0597.01//Financiadora de Estudos e Projetos/ ; 01.13.0315.00//Financiadora de Estudos e Projetos/ ; }, mesh = {2,4-Dichlorophenoxyacetic Acid ; Arecaceae/*cytology ; Culture Media ; Indoleacetic Acids ; Plant Cells/*ultrastructure ; *Plant Somatic Embryogenesis Techniques ; Trees ; }, abstract = {Somatic embryogenesis in palm trees is, in general, a slow and highly complex process, with a predominance of the indirect route and, consequently, a lack of knowledge about the direct route. We present new knowledge related to the morphological, histochemical and ultrastructural aspects of the transition from somatic to embryogenic cells and direct formation of somatic embryos from mature zygotic embryos of Syagrus oleracea, a palm tree. The results support the general concept that 2,4-dichlorophenoxyacetic acid plays a critical role for the formation of somatic embryos of direct and multicellular origin. Seven days in medium with auxin were enough for the identification of embryogenic cells. These cells had a set of characteristics corresponding to totipotent stem cells. At 14 days on induction medium, nodular formations were observed in the distal region of inoculated embryos, which evolved into globular somatic embryos. At 120 days on induction medium, the quality of the somatic embryos was compromised. The dynamics of the mobilization of reserve compounds was also demonstrated, with emphasis on starch and protein as energy sources required for the embryogenic process. This study shows for the first time the anatomical and ultrastructural events involved in direct somatic embryogenesis in a palm tree and incites the scientific community to return to the discussion of classical concepts related to direct somatic embryogenesis, especially regarding the characteristics and location of determined pre-embryogenic cells.}, } @article {pmid31512055, year = {2019}, author = {Alcorta, J and Vergara-Barros, P and Antonaru, LA and Alcamán-Arias, ME and Nürnberg, DJ and Díez, B}, title = {Fischerella thermalis: a model organism to study thermophilic diazotrophy, photosynthesis and multicellularity in cyanobacteria.}, journal = {Extremophiles : life under extreme conditions}, volume = {23}, number = {6}, pages = {635-647}, pmid = {31512055}, issn = {1433-4909}, support = {1150171//Fondo de Fomento al Desarrollo Científico y Tecnológico/ ; 1190998//Fondo de Fomento al Desarrollo Científico y Tecnológico/ ; }, mesh = {Acclimatization/*physiology ; *Biological Evolution ; Cyanobacteria/*physiology ; Hot Springs/*microbiology ; *Hot Temperature ; *Models, Biological ; Trichomes/physiology ; }, abstract = {The true-branching cyanobacterium Fischerella thermalis (also known as Mastigocladus laminosus) is widely distributed in hot springs around the world. Morphologically, it has been described as early as 1837. However, its taxonomic placement remains controversial. F. thermalis belongs to the same genus as mesophilic Fischerella species but forms a monophyletic clade of thermophilic Fischerella strains and sequences from hot springs. Their recent divergence from freshwater or soil true-branching species and the ongoing process of specialization inside the thermal gradient make them an interesting evolutionary model to study. F. thermalis is one of the most complex prokaryotes. It forms a cellular network in which the main trichome and branches exchange metabolites and regulators via septal junctions. This species can adapt to a variety of environmental conditions, with its photosynthetic apparatus remaining active in a temperature range from 15 to 58 °C. Together with its nitrogen-fixing ability, this allows it to dominate in hot spring microbial mats and contribute significantly to the de novo carbon and nitrogen input. Here, we review the current knowledge on the taxonomy and distribution of F. thermalis, its morphological complexity, and its physiological adaptations to an extreme environment.}, } @article {pmid31501435, year = {2019}, author = {Kiss, E and Hegedüs, B and Virágh, M and Varga, T and Merényi, Z and Kószó, T and Bálint, B and Prasanna, AN and Krizsán, K and Kocsubé, S and Riquelme, M and Takeshita, N and Nagy, LG}, title = {Comparative genomics reveals the origin of fungal hyphae and multicellularity.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {4080}, pmid = {31501435}, issn = {2041-1723}, mesh = {Evolution, Molecular ; Fungal Proteins/genetics/metabolism ; Fungi/*cytology/*genetics ; Genes, Fungal ; *Genomics ; Hyphae/*cytology/*genetics ; Morphogenesis/genetics ; Multigene Family ; Phagocytosis/genetics ; Phylogeny ; Yeasts/genetics ; }, abstract = {Hyphae represent a hallmark structure of multicellular fungi. The evolutionary origins of hyphae and of the underlying genes are, however, hardly known. By systematically analyzing 72 complete genomes, we here show that hyphae evolved early in fungal evolution probably via diverse genetic changes, including co-option and exaptation of ancient eukaryotic (e.g. phagocytosis-related) genes, the origin of new gene families, gene duplications and alterations of gene structure, among others. Contrary to most multicellular lineages, the origin of filamentous fungi did not correlate with expansions of kinases, receptors or adhesive proteins. Co-option was probably the dominant mechanism for recruiting genes for hypha morphogenesis, while gene duplication was apparently less prevalent, except in transcriptional regulators and cell wall - related genes. We identified 414 novel gene families that show correlated evolution with hyphae and that may have contributed to its evolution. Our results suggest that hyphae represent a unique multicellular organization that evolved by limited fungal-specific innovations and gene duplication but pervasive co-option and modification of ancient eukaryotic functions.}, } @article {pmid31480977, year = {2019}, author = {Fisher, RM and Regenberg, B}, title = {Multicellular group formation in Saccharomyces cerevisiae.}, journal = {Proceedings. Biological sciences}, volume = {286}, number = {1910}, pages = {20191098}, pmid = {31480977}, issn = {1471-2954}, mesh = {Biological Evolution ; Phenotype ; Saccharomyces cerevisiae/*physiology ; }, abstract = {Understanding how and why cells cooperate to form multicellular organisms is a central aim of evolutionary biology. Multicellular groups can form through clonal development (where daughter cells stick to mother cells after division) or by aggregation (where cells aggregate to form groups). These different ways of forming groups directly affect relatedness between individual cells, which in turn can influence the degree of cooperation and conflict within the multicellular group. It is hard to study the evolution of multicellularity by focusing only on obligately multicellular organisms, like complex animals and plants, because the factors that favour multicellular cooperation cannot be disentangled, as cells cannot survive and reproduce independently. We support the use of Saccharomyces cerevisiae as an ideal model for studying the very first stages of the evolution of multicellularity. This is because it can form multicellular groups both clonally and through aggregation and uses a family of proteins called 'flocculins' that determine the way in which groups form, making it particularly amenable to laboratory experiments. We briefly review current knowledge about multicellularity in S. cerevisiae and then propose a framework for making predictions about the evolution of multicellular phenotypes in yeast based on social evolution theory. We finish by explaining how S. cerevisiae is a particularly useful experimental model for the analysis of open questions concerning multicellularity.}, } @article {pmid31478136, year = {2019}, author = {Hartenstein, V and Martinez, P}, title = {Structure, development and evolution of the digestive system.}, journal = {Cell and tissue research}, volume = {377}, number = {3}, pages = {289-292}, pmid = {31478136}, issn = {1432-0878}, support = {R01 NS054814/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Digestion ; Digestive System/*cytology ; Immune System/physiology ; Phagocytosis/physiology ; }, abstract = {Living cells depend on a constant supply of energy-rich organic molecules from the environment. Small molecules pass into the interior of the cell via simple diffusion or active transport carried out by membrane bound transporters; macromolecules, or entire cells, are taken up by endocytosis/phagocytosis, and are degraded intracellularly in specialized membrane bound compartments (lysosomes). Whereas all cells are capable of transporting molecules through the membrane, the efficient procurement, digestion and uptake of nutrients have become the function of specialized cell types and organs, forming the digestive system in multicellular animals. In mammals, for example, the digestive system is comprised of glandular organs with classes of cells specialized in the secretion of enzymes for the extracellular digestion of food particles (e.g., exocrine cells of the salivary gland, pancreas), as well as other organs with absorptive function (e.g., small intestine). Numerous other cell types, such as smooth muscle cells, neurons and enteroendocrine cells, are associated with glandular cells and intestinal cells to promote the digestive process.}, } @article {pmid31474536, year = {2019}, author = {Gonçalves, AP and Heller, J and Span, EA and Rosenfield, G and Do, HP and Palma-Guerrero, J and Requena, N and Marletta, MA and Glass, NL}, title = {Allorecognition upon Fungal Cell-Cell Contact Determines Social Cooperation and Impacts the Acquisition of Multicellularity.}, journal = {Current biology : CB}, volume = {29}, number = {18}, pages = {3006-3017.e3}, doi = {10.1016/j.cub.2019.07.060}, pmid = {31474536}, issn = {1879-0445}, support = {S10 RR029668/RR/NCRR NIH HHS/United States ; S10 RR027303/RR/NCRR NIH HHS/United States ; }, mesh = {Alleles ; Amino Acid Sequence/genetics ; Cell Communication/*genetics/physiology ; Cell Fusion ; Cell Wall/*genetics/*metabolism ; Evolution, Molecular ; Fungal Proteins/genetics/metabolism ; Genes, Fungal/genetics ; Neurospora crassa/genetics/growth & development ; Phylogeny ; Polymorphism, Genetic/genetics ; }, abstract = {Somatic cell fusion and conspecific cooperation are crucial social traits for microbial unicellular-to-multicellular transitions, colony expansion, and substrate foraging but are also associated with risks of parasitism. We identified a cell wall remodeling (cwr) checkpoint that acts upon cell contact to assess genetic compatibility and regulate cell wall dissolution during somatic cell fusion in a wild population of the filamentous fungus Neurospora crassa. Non-allelic interactions between two linked loci, cwr-1 and cwr-2, were necessary and sufficient to block cell fusion: cwr-1 encodes a polysaccharide monooxygenase (PMO), a class of enzymes associated with extracellular degradative capacities, and cwr-2 encodes a predicted transmembrane protein. Mutations of sites in CWR-1 essential for PMO catalytic activity abolished the block in cell fusion between formerly incompatible strains. In Neurospora, alleles cwr-1 and cwr-2 were highly polymorphic, fell into distinct haplogroups, and showed trans-species polymorphisms. Distinct haplogroups and trans-species polymorphisms at cwr-1 and cwr-2 were also identified in the distantly related genus Fusarium, suggesting convergent evolution. Proteins involved in chemotropic processes showed extended localization at contact sites, suggesting that cwr regulates the transition between chemotropic growth and cell wall dissolution. Our work revealed an allorecognition surveillance system based on kind discrimination that inhibits cooperative behavior in fungi by blocking cell fusion upon contact, contributing to fungal immunity by preventing formation of chimeras between genetically non-identical colonies.}, } @article {pmid31463010, year = {2019}, author = {Vostinar, AE and Goldsby, HJ and Ofria, C}, title = {Suicidal selection: Programmed cell death can evolve in unicellular organisms due solely to kin selection.}, journal = {Ecology and evolution}, volume = {9}, number = {16}, pages = {9129-9136}, pmid = {31463010}, issn = {2045-7758}, abstract = {ABSTRACT: Unicellular organisms can engage in a process by which a cell purposefully destroys itself, termed programmed cell death (PCD). While it is clear that the death of specific cells within a multicellular organism could increase inclusive fitness (e.g., during development), the origin of PCD in unicellular organisms is less obvious. Kin selection has been shown to help maintain instances of PCD in existing populations of unicellular organisms; however, competing hypotheses exist about whether additional factors are necessary to explain its origin. Those factors could include an environmental shift that causes latent PCD to be expressed, PCD hitchhiking on a large beneficial mutation, and PCD being simply a common pathology. Here, we present results using an artificial life model to demonstrate that kin selection can, in fact, be sufficient to give rise to PCD in unicellular organisms. Furthermore, when benefits to kin are direct-that is, resources provided to nearby kin-PCD is more beneficial than when benefits are indirect-that is, nonkin are injured, thus increasing the relative amount of resources for kin. Finally, when considering how strict organisms are in determining kin or nonkin (in terms of mutations), direct benefits are viable in a narrower range than indirect benefits.

OPEN RESEARCH BADGES: This article has been awarded Open Data and Open Materials Badges. All materials and data are publicly accessible via the Open Science Framework at https://github.com/anyaevostinar/SuicidalAltruismDissertation/tree/master/LongTerm.}, } @article {pmid31462290, year = {2019}, author = {Romero-Mujalli, D and Jeltsch, F and Tiedemann, R}, title = {Elevated mutation rates are unlikely to evolve in sexual species, not even under rapid environmental change.}, journal = {BMC evolutionary biology}, volume = {19}, number = {1}, pages = {175}, pmid = {31462290}, issn = {1471-2148}, mesh = {Adaptation, Physiological ; Biological Evolution ; *Climate Change ; Computer Simulation ; Ecosystem ; Extinction, Biological ; Mutation ; *Mutation Rate ; Population Density ; Reproduction ; }, abstract = {BACKGROUND: Organisms are expected to respond to changing environmental conditions through local adaptation, range shift or local extinction. The process of local adaptation can occur by genetic changes or phenotypic plasticity, and becomes especially relevant when dispersal abilities or possibilities are somehow constrained. For genetic changes to occur, mutations are the ultimate source of variation and the mutation rate in terms of a mutator locus can be subject to evolutionary change. Recent findings suggest that the evolution of the mutation rate in a sexual species can advance invasion speed and promote adaptation to novel environmental conditions. Following this idea, this work uses an individual-based model approach to investigate if the mutation rate can also evolve in a sexual species experiencing different conditions of directional climate change, under different scenarios of colored stochastic environmental noise, probability of recombination and of beneficial mutations. The color of the noise mimicked investigating the evolutionary dynamics of the mutation rate in different habitats.

RESULTS: The results suggest that the mutation rate in a sexual species experiencing directional climate change scenarios can evolve and reach relatively high values mainly under conditions of complete linkage of the mutator locus and the adaptation locus. In contrast, when they are unlinked, the mutation rate can slightly increase only under scenarios where at least 50% of arising mutations are beneficial and the rate of environmental change is relatively fast. This result is robust under different scenarios of stochastic environmental noise, which supports the observation of no systematic variation in the mutation rate among organisms experiencing different habitats.

CONCLUSIONS: Given that 50% beneficial mutations may be an unrealistic assumption, and that recombination is ubiquitous in sexual species, the evolution of an elevated mutation rate in a sexual species experiencing directional climate change might be rather unlikely. Furthermore, when the percentage of beneficial mutations and the population size are small, sexual species (especially multicellular ones) producing few offspring may be expected to react to changing environments not by adaptive genetic change, but mainly through plasticity. Without the ability for a plastic response, such species may become - at least locally - extinct.}, } @article {pmid31456065, year = {2019}, author = {Cleri, F}, title = {Agent-based model of multicellular tumor spheroid evolution including cell metabolism.}, journal = {The European physical journal. E, Soft matter}, volume = {42}, number = {8}, pages = {112}, pmid = {31456065}, issn = {1292-895X}, mesh = {Adenosine Triphosphate/metabolism ; Animals ; Carcinogenesis/genetics/*metabolism/pathology ; *Clonal Evolution ; DNA Damage ; Glucose/metabolism ; Humans ; Markov Chains ; *Models, Theoretical ; Oxygen/metabolism ; Spheroids, Cellular/*metabolism/pathology ; Tumor Cells, Cultured ; }, abstract = {Computational models aiming at the spatio-temporal description of cancer evolution are a suitable framework for testing biological hypotheses from experimental data, and generating new ones. Building on our recent work (J. Theor. Biol. 389, 146 (2016)) we develop a 3D agent-based model, capable of tracking hundreds of thousands of interacting cells, over time scales ranging from seconds to years. Cell dynamics is driven by a Monte Carlo solver, incorporating partial differential equations to describe chemical pathways and the activation/repression of "genes", leading to the up- or down-regulation of specific cell markers. Each cell-agent of different kind (stem, cancer, stromal etc.) runs through its cycle, undergoes division, can exit to a dormant, senescent, necrotic state, or apoptosis, according to the inputs from its systemic network. The basic network at this stage describes glucose/oxygen/ATP cycling, and can be readily extended to cancer-cell specific markers. Eventual accumulation of chemical/radiation damage to each cell's DNA is described by a Markov chain of internal states, and by a damage-repair network, whose evolution is linked to the cell systemic network. Aimed at a direct comparison with experiments of tumorsphere growth from stem cells, the present model will allow to quantitatively study the role of transcription factors involved in the reprogramming and variable radio-resistance of simulated cancer-stem cells, evolving in a realistic computer simulation of a growing multicellular tumorsphere.}, } @article {pmid31451789, year = {2019}, author = {Bruno, L and Ramlall, V and Studer, RA and Sauer, S and Bradley, D and Dharmalingam, G and Carroll, T and Ghoneim, M and Chopin, M and Nutt, SL and Elderkin, S and Rueda, DS and Fisher, AG and Siggers, T and Beltrao, P and Merkenschlager, M}, title = {Selective deployment of transcription factor paralogs with submaximal strength facilitates gene regulation in the immune system.}, journal = {Nature immunology}, volume = {20}, number = {10}, pages = {1372-1380}, pmid = {31451789}, issn = {1529-2916}, support = {MC_U120027516/MRC_/Medical Research Council/United Kingdom ; 099276/WT_/Wellcome Trust/United Kingdom ; MC_UP_1102/5/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; R01 AI116829/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Cell Lineage ; Conserved Sequence ; Core Binding Factor alpha Subunits/*genetics ; Evolution, Molecular ; Gene Duplication ; Humans ; Immune System/*physiology ; Langerhans Cells/*physiology ; Mammals ; Organ Specificity/*genetics ; Signal Transduction ; T-Lymphocytes, Regulatory/*physiology ; Transcriptome ; }, abstract = {In multicellular organisms, duplicated genes can diverge through tissue-specific gene expression patterns, as exemplified by highly regulated expression of RUNX transcription factor paralogs with apparent functional redundancy. Here we asked what cell-type-specific biologies might be supported by the selective expression of RUNX paralogs during Langerhans cell and inducible regulatory T cell differentiation. We uncovered functional nonequivalence between RUNX paralogs. Selective expression of native paralogs allowed integration of transcription factor activity with extrinsic signals, while non-native paralogs enforced differentiation even in the absence of exogenous inducers. DNA binding affinity was controlled by divergent amino acids within the otherwise highly conserved RUNT domain and evolutionary reconstruction suggested convergence of RUNT domain residues toward submaximal strength. Hence, the selective expression of gene duplicates in specialized cell types can synergize with the acquisition of functional differences to enable appropriate gene expression, lineage choice and differentiation in the mammalian immune system.}, } @article {pmid31446445, year = {2019}, author = {Annunziata, R and Andrikou, C and Perillo, M and Cuomo, C and Arnone, MI}, title = {Development and evolution of gut structures: from molecules to function.}, journal = {Cell and tissue research}, volume = {377}, number = {3}, pages = {445-458}, doi = {10.1007/s00441-019-03093-9}, pmid = {31446445}, issn = {1432-0878}, support = {215781//Marie Curie ITN EVONET/ ; }, mesh = {Animals ; Biological Evolution ; *Gastrointestinal Tract/cytology/physiology ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Larva/physiology ; Sea Urchins/genetics/*physiology ; Starfish/genetics/*physiology ; Vertebrates/genetics/*physiology ; }, abstract = {The emergence of a specialized system for food digestion and nutrient absorption was a crucial innovation for multicellular organisms. Digestive systems with different levels of complexity evolved in different animals, with the endoderm-derived one-way gut of most bilaterians to be the prevailing and more specialized form. While the molecular events regulating the early phases of embryonic tissue specification have been deeply investigated in animals occupying different phylogenetic positions, the mechanisms underlying gut patterning and gut-associated structures differentiation are still mostly obscure. In this review, we describe the main discoveries in gut and gut-associated structures development in echinoderm larvae (mainly for sea urchin and, when available, for sea star) and compare them with existing information in vertebrates. An impressive degree of conservation emerges when comparing the transcription factor toolkits recruited for gut cells and tissue differentiation in animals as diverse as echinoderms and vertebrates, thus suggesting that their function emerged in the deuterostome ancestor.}, } @article {pmid31444931, year = {2019}, author = {Wu, F and Ma, C and Han, B and Meng, L and Hu, H and Fang, Y and Feng, M and Zhang, X and Rueppell, O and Li, J}, title = {Behavioural, physiological and molecular changes in alloparental caregivers may be responsible for selection response for female reproductive investment in honey bees.}, journal = {Molecular ecology}, volume = {28}, number = {18}, pages = {4212-4227}, doi = {10.1111/mec.15207}, pmid = {31444931}, issn = {1365-294X}, mesh = {Amino Acid Sequence ; Animals ; Arthropod Antennae/physiology ; Bees/*genetics/*physiology ; Behavior, Animal/*physiology ; Fatty Acids ; Female ; Genetic Association Studies ; Honey ; Insect Proteins/chemistry/metabolism ; Larva/physiology ; Pheromones/chemistry/metabolism ; Proteome/metabolism ; Proteomics ; Reproduction ; Volatile Organic Compounds/analysis ; }, abstract = {Reproductive investment is a central life history variable that influences all aspects of life. Hormones coordinate reproduction in multicellular organisms, but the mechanisms controlling the collective reproductive investment of social insects are largely unexplored. One important aspect of honey bee (Apis mellifera) reproductive investment consists of raising female-destined larvae into new queens by alloparental care of nurse bees in form of royal jelly provisioning. Artificial selection for commercial royal jelly production over 40 years has increased this reproductive investment by an order of magnitude. In a cross-fostering experiment, we establish that this shift in social phenotype is caused by nurse bees. We find no evidence for changes in larval signalling. Instead, the antennae of the nurse bees of the selected stock are more responsive to brood pheromones than control bees. Correspondingly, the selected royal jelly bee nurses are more attracted to brood pheromones than unselected control nurses. Comparative proteomics of the antennae from the selected and unselected stocks indicate putative molecular mechanisms, primarily changes in chemosensation and energy metabolism. We report expression differences of several candidate genes that correlate with the differences in reproductive investment. The functional relevance of these genes is supported by demonstrating that the corresponding proteins can competitively bind one previously described and one newly discovered brood pheromone. Thus, we suggest several chemosensory genes, most prominently OBP16 and CSP4, as candidate mechanisms controlling queen rearing, a key reproductive investment, in honey bees. These findings reveal novel aspects of pheromonal communication in honey bees and explain how sensory changes affect communication and lead to a drastic shift in colony-level resource allocation to sexual reproduction. Thus, pheromonal and hormonal communication may play similar roles for reproductive investment in superorganisms and multicellular organisms, respectively.}, } @article {pmid31444229, year = {2019}, author = {Draper, GW and Shoemark, DK and Adams, JC}, title = {Modelling the early evolution of extracellular matrix from modern Ctenophores and Sponges.}, journal = {Essays in biochemistry}, volume = {63}, number = {3}, pages = {389-405}, doi = {10.1042/EBC20180048}, pmid = {31444229}, issn = {1744-1358}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Ctenophora/*chemistry/genetics ; Extracellular Matrix/*genetics ; Extracellular Matrix Proteins/*analysis/chemistry/genetics ; Genomics ; Porifera/*chemistry/genetics ; Protein Domains ; Proteome/analysis ; Transcriptome ; }, abstract = {Animals (metazoans) include some of the most complex living organisms on Earth, with regard to their multicellularity, numbers of differentiated cell types, and lifecycles. The metazoan extracellular matrix (ECM) is well-known to have major roles in the development of tissues during embryogenesis and in maintaining homoeostasis throughout life, yet insight into the ECM proteins which may have contributed to the transition from unicellular eukaryotes to multicellular animals remains sparse. Recent phylogenetic studies place either ctenophores or poriferans as the closest modern relatives of the earliest emerging metazoans. Here, we review the literature and representative genomic and transcriptomic databases for evidence of ECM and ECM-affiliated components known to be conserved in bilaterians, that are also present in ctenophores and/or poriferans. Whereas an extensive set of related proteins are identifiable in poriferans, there is a strikingly lack of conservation in ctenophores. From this perspective, much remains to be learnt about the composition of ctenophore mesoglea. The principal ECM-related proteins conserved between ctenophores, poriferans, and bilaterians include collagen IV, laminin-like proteins, thrombospondin superfamily members, integrins, membrane-associated proteoglycans, and tissue transglutaminase. These are candidates for a putative ancestral ECM that may have contributed to the emergence of the metazoans.}, } @article {pmid31443631, year = {2019}, author = {Rozhok, A and DeGregori, J}, title = {Somatic maintenance impacts the evolution of mutation rate.}, journal = {BMC evolutionary biology}, volume = {19}, number = {1}, pages = {172}, pmid = {31443631}, issn = {1471-2148}, support = {R01 CA180175/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Body Size ; Computer Simulation ; Longevity ; *Models, Genetic ; Monte Carlo Method ; Mutation ; *Mutation Rate ; Neoplasms/genetics ; Phenotype ; Population Density ; Selection, Genetic ; }, abstract = {BACKGROUND: The evolution of multi-cellular animals has produced a conspicuous trend toward increased body size. This trend has introduced at least two novel problems: an expected elevated risk of somatic disorders, such as cancer, and declining evolvability due to generally reduced population size, lower reproduction rate and extended generation time. Low population size is widely recognized to explain the high mutation rates in animals by limiting the presumed universally negative selection acting on mutation rates.

RESULTS: Here, we present evidence from stochastic modeling that the direction and strength of selection acting on mutation rates is highly dependent on the evolution of somatic maintenance, and thus longevity, which modulates the cost of somatic mutations.

CONCLUSIONS: We argue that the impact of the evolution of longevity on mutation rates may have been critical in facilitating animal evolution.}, } @article {pmid31430180, year = {2019}, author = {D'Ario, M and Sablowski, R}, title = {Cell Size Control in Plants.}, journal = {Annual review of genetics}, volume = {53}, number = {}, pages = {45-65}, doi = {10.1146/annurev-genet-112618-043602}, pmid = {31430180}, issn = {1545-2948}, support = {BBS/E/J/00000594/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P013511/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M003825/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Cell Size ; DNA Replication ; Eukaryotic Cells/cytology ; Meristem/*cytology/growth & development ; Mitosis ; Models, Biological ; Plant Cells/*physiology ; Plant Development/genetics ; *Ploidies ; Yeasts/cytology/genetics ; }, abstract = {The genetic control of the characteristic cell sizes of different species and tissues is a long-standing enigma. Plants are convenient for studying this question in a multicellular context, as their cells do not move and are easily tracked and measured from organ initiation in the meristems to subsequent morphogenesis and differentiation. In this article, we discuss cell size control in plants compared with other organisms. As seen from yeast cells to mammalian cells, size homeostasis is maintained cell autonomously in the shoot meristem. In developing organs, vacuolization contributes to cell size heterogeneity and may resolve conflicts between growth control at the cellular and organ levels. Molecular mechanisms for cell size control have implications for how cell size responds to changes in ploidy, which are particularly important in plant development and evolution. We also discuss comparatively the functional consequences of cell size and their potential repercussions at higher scales, including genome evolution.}, } @article {pmid31427514, year = {2019}, author = {Kjeldsen, KU and Schreiber, L and Thorup, CA and Boesen, T and Bjerg, JT and Yang, T and Dueholm, MS and Larsen, S and Risgaard-Petersen, N and Nierychlo, M and Schmid, M and Bøggild, A and van de Vossenberg, J and Geelhoed, JS and Meysman, FJR and Wagner, M and Nielsen, PH and Nielsen, LP and Schramm, A}, title = {On the evolution and physiology of cable bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {38}, pages = {19116-19125}, pmid = {31427514}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Bacterial Proteins/genetics/*metabolism ; *Biological Evolution ; Carbon Cycle ; Cell Movement ; Chemotaxis ; Cytochromes/metabolism ; Deltaproteobacteria/classification/*genetics/*physiology ; Electron Transport ; *Genome, Bacterial ; Geologic Sediments/microbiology ; Nitrates/metabolism ; Oxidation-Reduction ; Oxygen/metabolism ; Phylogeny ; Proteome/*analysis ; Sequence Homology ; Sulfides/metabolism ; }, abstract = {Cable bacteria of the family Desulfobulbaceae form centimeter-long filaments comprising thousands of cells. They occur worldwide in the surface of aquatic sediments, where they connect sulfide oxidation with oxygen or nitrate reduction via long-distance electron transport. In the absence of pure cultures, we used single-filament genomics and metagenomics to retrieve draft genomes of 3 marine Candidatus Electrothrix and 1 freshwater Ca. Electronema species. These genomes contain >50% unknown genes but still share their core genomic makeup with sulfate-reducing and sulfur-disproportionating Desulfobulbaceae, with few core genes lost and 212 unique genes (from 197 gene families) conserved among cable bacteria. Last common ancestor analysis indicates gene divergence and lateral gene transfer as equally important origins of these unique genes. With support from metaproteomics of a Ca. Electronema enrichment, the genomes suggest that cable bacteria oxidize sulfide by reversing the canonical sulfate reduction pathway and fix CO2 using the Wood-Ljungdahl pathway. Cable bacteria show limited organotrophic potential, may assimilate smaller organic acids and alcohols, fix N2, and synthesize polyphosphates and polyglucose as storage compounds; several of these traits were confirmed by cell-level experimental analyses. We propose a model for electron flow from sulfide to oxygen that involves periplasmic cytochromes, yet-unidentified conductive periplasmic fibers, and periplasmic oxygen reduction. This model proposes that an active cable bacterium gains energy in the anodic, sulfide-oxidizing cells, whereas cells in the oxic zone flare off electrons through intense cathodic oxygen respiration without energy conservation; this peculiar form of multicellularity seems unparalleled in the microbial world.}, } @article {pmid31419316, year = {2020}, author = {Fan, X and Han, W and Teng, L and Jiang, P and Zhang, X and Xu, D and Li, C and Pellegrini, M and Wu, C and Wang, Y and Kaczurowski, MJS and Lin, X and Tirichine, L and Mock, T and Ye, N}, title = {Single-base methylome profiling of the giant kelp Saccharina japonica reveals significant differences in DNA methylation to microalgae and plants.}, journal = {The New phytologist}, volume = {225}, number = {1}, pages = {234-249}, pmid = {31419316}, issn = {1469-8137}, mesh = {Chromosomes, Plant/genetics ; Cytosine/metabolism ; DNA Methylation/*genetics ; Evolution, Molecular ; Gene Expression Regulation, Plant ; Genome, Plant ; Heterozygote ; Kelp/*genetics ; Methyltransferases/genetics/metabolism ; Microalgae/*genetics ; Oxidoreductases, O-Demethylating/metabolism ; Plants/*genetics ; Promoter Regions, Genetic/genetics ; Transcriptome/genetics ; }, abstract = {Brown algae have convergently evolved plant-like body plans and reproductive cycles, which in plants are controlled by differential DNA methylation. This contribution provides the first single-base methylome profiles of haploid gametophytes and diploid sporophytes of a multicellular alga. Although only c. 1.4% of cytosines in Saccharina japonica were methylated mainly at CHH sites and characterized by 5-methylcytosine (5mC), there were significant differences between life-cycle stages. DNA methyltransferase 2 (DNMT2), known to efficiently catalyze tRNA methylation, is assumed to methylate the genome of S. japonica in the structural context of tRNAs as the genome does not encode any other DNA methyltransferases. Circular and long noncoding RNA genes were the most strongly methylated regulatory elements in S. japonica. Differential expression of genes was negatively correlated with DNA methylation with the highest methylation levels measured in both haploid gametophytes. Hypomethylated and highly expressed genes in diploid sporophytes included genes involved in morphogenesis and halogen metabolism. The data herein provide evidence that cytosine methylation, although occurring at a low level, is significantly contributing to the formation of different life-cycle stages, tissue differentiation and metabolism in brown algae.}, } @article {pmid31417709, year = {2019}, author = {Lou, Y and Chen, A and Yoshida, E and Chen, Y}, title = {Homeostasis and systematic ageing as non-equilibrium phase transitions in computational multicellular organizations.}, journal = {Royal Society open science}, volume = {6}, number = {7}, pages = {190012}, pmid = {31417709}, issn = {2054-5703}, abstract = {Being a fatal threat to life, the breakdown of homeostasis in tissues is believed to involve multiscale factors ranging from the accumulation of genetic damages to the deregulation of metabolic processes. Here, we present a prototypical multicellular homeostasis model in the form of a two-dimensional stochastic cellular automaton with three cellular states, cell division, cell death and cell cycle arrest, of which the state-updating rules are based on fundamental cell biology. Despite the simplicity, this model illustrates how multicellular organizations can develop into diverse homeostatic patterns with distinct morphologies, turnover rates and lifespans without considering genetic, metabolic or other exogenous variations. Through mean-field analysis and Monte-Carlo simulations, those homeostatic states are found to be classified into extinctive, proliferative and degenerative phases, whereas healthy multicellular organizations evolve from proliferative to degenerative phases over a long time, undergoing a systematic ageing akin to a transition into an absorbing state in non-equilibrium physical systems. It is suggested that the collapse of homeostasis at the multicellular level may originate from the fundamental nature of cell biology regarding the physics of some non-equilibrium processes instead of subcellular details.}, } @article {pmid31417549, year = {2019}, author = {Kim, HR and Jun, CD}, title = {T Cell Microvilli: Sensors or Senders?.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {1753}, pmid = {31417549}, issn = {1664-3224}, mesh = {Animals ; Antigen-Presenting Cells/cytology/*immunology ; Cell Communication/*immunology ; Cell-Derived Microparticles/*immunology ; Exosomes/*immunology ; Humans ; Microvilli/*immunology ; T-Lymphocytes/cytology/*immunology ; }, abstract = {Communication between cells is essential for multicellular life. During cognate immune interactions, T cells communicate with antigen-presenting cells (APC) via direct cell-cell contact or the release of molecules and vesicles containing T cell messages. A wide variety of mechanisms have been reported and among them a process called "trogocytosis" has traditionally been thought to be the fastest way to directly transfer membrane portions containing intact proteins from one cell to another; however, the mechanism is unverified. Trogocytosis has been distinguished from the generation of extracellular vesicles (EVs), a term that encompasses exosomes and microvesicles, as EVs are released via a contact-independent manner and are suggested to potentially send molecular messages over a distance. However, some previous reports regarding EVs in T cells may be misleading in terms of explaining their cellular origins. In addition, there is little evidence on how EVs are generated from T cells in vivo and function to regulate complex immune responses. A recent work demonstrated that T cell microvilli-thin and finger-like membrane protrusions-are highly fragile and easily separated as membrane particles by trogocytosis, forming a new class of EVs. Surprisingly, released T cell microvilli-derived particles act as vectors, transmitting T cell messages to cognate APCs. This review focuses on how T cell microvilli vesicles are connected with immune regulation mechanisms discovered previously.}, } @article {pmid31415772, year = {2020}, author = {Miller, WB and Torday, JS and Baluška, F}, title = {The N-space Episenome unifies cellular information space-time within cognition-based evolution.}, journal = {Progress in biophysics and molecular biology}, volume = {150}, number = {}, pages = {112-139}, doi = {10.1016/j.pbiomolbio.2019.08.006}, pmid = {31415772}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Cell Communication ; Cell Physiological Phenomena ; Cells ; Cognition/*physiology ; Genome ; *Homeostasis ; Humans ; Morphogenesis/*genetics ; Time Factors ; }, abstract = {Self-referential cellular homeostasis is maintained by the measured assessment of both internal status and external conditions based within an integrated cellular information field. This cellular field attachment to biologic information space-time coordinates environmental inputs by connecting the cellular senome, as the sum of the sensory experiences of the cell, with its genome and epigenome. In multicellular organisms, individual cellular information fields aggregate into a collective information architectural matrix, termed a N-space Episenome, that enables mutualized organism-wide information management. It is hypothesized that biological organization represents a dual heritable system constituted by both its biological materiality and a conjoining N-space Episenome. It is further proposed that morphogenesis derives from reciprocations between these inter-related facets to yield coordinated multicellular growth and development. The N-space Episenome is conceived as a whole cell informational projection that is heritable, transferable via cell division and essential for the synchronous integration of the diverse self-referential cells that constitute holobionts.}, } @article {pmid31413788, year = {2019}, author = {Fields, C and Levin, M}, title = {Somatic multicellularity as a satisficing solution to the prediction-error minimization problem.}, journal = {Communicative & integrative biology}, volume = {12}, number = {1}, pages = {119-132}, pmid = {31413788}, issn = {1942-0889}, abstract = {Adaptive success in the biosphere requires the dynamic ability to adjust physiological, transcriptional, and behavioral responses to environmental conditions. From chemical networks to organisms to whole communities, biological entities at all levels of organization seek to optimize their predictive power. Here, we argue that this fundamental drive provides a novel perspective on the origin of multicellularity. One way for unicellular organisms to minimize surprise with respect to external inputs is to be surrounded by reproductively-disabled, i.e. somatic copies of themselves - highly predictable agents which in effect reduce uncertainty in their microenvironments. We show that the transition to multicellularity can be modeled as a phase transition driven by environmental threats. We present modeling results showing how multicellular bodies can arise if non-reproductive somatic cells protect their reproductive parents from environmental lethality. We discuss how a somatic body can be interpreted as a Markov blanket around one or more reproductive cells, and how the transition to somatic multicellularity can be represented as a transition from exposure of reproductive cells to a high-uncertainty environment to their protection from environmental uncertainty by this Markov blanket. This is, effectively, a transition by the Markov blanket from transparency to opacity for the variational free energy of the environment. We suggest that the ability to arrest the cell cycle of daughter cells and redirect their resource utilization from division to environmental threat amelioration is the key innovation of obligate multicellular eukaryotes, that the nervous system evolved to exercise this control over long distances, and that cancer is an escape by somatic cells from the control of reproductive cells. Our quantitative model illustrates the evolutionary dynamics of this system, provides a novel hypothesis for the origin of multicellular animal bodies, and suggests a fundamental link between the architectures of complex organisms and information processing in proto-cognitive cellular agents.}, } @article {pmid31410258, year = {2019}, author = {Kuzdzal-Fick, JJ and Chen, L and Balázsi, G}, title = {Disadvantages and benefits of evolved unicellularity versus multicellularity in budding yeast.}, journal = {Ecology and evolution}, volume = {9}, number = {15}, pages = {8509-8523}, pmid = {31410258}, issn = {2045-7758}, support = {DP2 OD006481/OD/NIH HHS/United States ; R01 AI127704/AI/NIAID NIH HHS/United States ; R35 GM122561/GM/NIGMS NIH HHS/United States ; }, abstract = {Multicellular organisms appeared on Earth through several independent major evolutionary transitions. Are such transitions reversible? Addressing this fundamental question entails understanding the benefits and costs of multicellularity versus unicellularity. For example, some wild yeast strains form multicellular clumps, which might be beneficial in stressful conditions, but this has been untested. Here, we show that unicellular yeast evolve from clump-forming ancestors by propagating samples from suspension after larger clumps have settled. Unicellular yeast strains differed from their clumping ancestors mainly by mutations in the AMN1 (Antagonist of Mitotic exit Network) gene. Ancestral yeast clumps were more resistant to freeze/thaw, hydrogen peroxide, and ethanol stressors than their unicellular counterparts, but they grew slower without stress. These findings suggest disadvantages and benefits to multicellularity and unicellularity that may have impacted the emergence of multicellular life forms.}, } @article {pmid31409661, year = {2019}, author = {Small, CM and Currey, M and Beck, EA and Bassham, S and Cresko, WA}, title = {Highly Reproducible 16S Sequencing Facilitates Measurement of Host Genetic Influences on the Stickleback Gut Microbiome.}, journal = {mSystems}, volume = {4}, number = {4}, pages = {}, pmid = {31409661}, issn = {2379-5077}, abstract = {Multicellular organisms interact with resident microbes in important ways, and a better understanding of host-microbe interactions is aided by tools such as high-throughput 16S sequencing. However, rigorous evaluation of the veracity of these tools in a different context from which they were developed has often lagged behind. Our goal was to perform one such critical test by examining how variation in tissue preparation and DNA isolation could affect inferences about gut microbiome variation between two genetically divergent lines of threespine stickleback fish maintained in the same laboratory environment. Using careful experimental design and intensive sampling of individuals, we addressed technical and biological sources of variation in 16S-based estimates of microbial diversity. After employing a two-tiered bead beating approach that comprised tissue homogenization followed by microbial lysis in subsamples, we found an extremely minor effect of DNA isolation protocol relative to among-host microbial diversity differences. Abundance estimates for rare operational taxonomic units (OTUs), however, showed much lower reproducibility. Gut microbiome composition was highly variable across fish-even among cohoused siblings-relative to technical replicates, but a subtle effect of host genotype (stickleback line) was nevertheless detected for some microbial taxa.IMPORTANCE Our findings demonstrate the importance of appropriately quantifying biological and technical variance components when attempting to understand major influences on high-throughput microbiome data. Our focus was on understanding among-host (biological) variance in community metrics and its magnitude in relation to within-host (technical) variance, because meaningful comparisons among individuals are necessary in addressing major questions in host-microbe ecology and evolution, such as heritability of the microbiome. Our study design and insights should provide a useful example for others desiring to quantify microbiome variation at biological levels in the face of various technical factors in a variety of systems.}, } @article {pmid31384725, year = {2019}, author = {Blum, P and Payne, S}, title = {Evidence of an Epigenetics System in Archaea.}, journal = {Epigenetics insights}, volume = {12}, number = {}, pages = {2516865719865280}, pmid = {31384725}, issn = {2516-8657}, abstract = {Changes in the phenotype of a cell or organism that are heritable but do not involve changes in DNA sequence are referred to as epigenetic. They occur primarily through the gain or loss of chemical modification of chromatin protein or DNA. Epigenetics is therefore a non-Mendelian process. The study of epigenetics in eukaryotes is expanding with advances in knowledge about the relationship between mechanism and phenotype and as a requirement for multicellularity and cancer. However, life also includes other groups or domains, notably the bacteria and archaea. The occurrence of epigenetics in these deep lineages is an emerging topic accompanied by controversy. In these non-eukaryotic organisms, epigenetics is critically important because it stimulates new evolutionary theory and refines perspective about biological action.}, } @article {pmid31380606, year = {2019}, author = {Newman, SA}, title = {Inherent forms and the evolution of evolution.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {8}, pages = {331-338}, doi = {10.1002/jez.b.22895}, pmid = {31380606}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; Chlorophyta ; Developmental Biology ; Dictyosteliida ; Morphogenesis ; }, abstract = {John Bonner presented a provocative conjecture that the means by which organisms evolve has itself evolved. The elements of his postulated nonuniformitarianism in the essay under discussion-the emergence of sex, the enhanced selection pressures on larger multicellular forms-center on a presumed close mapping of genotypic to phenotypic change. A different view emerges from delving into earlier work of Bonner's in which he proposed the concept of "neutral phenotypes" and "neutral morphologies" allied to D'Arcy Thompson's analysis of physical determinants of form and studied the conditional elicitation of intrinsic organizational properties of cell aggregates in social amoebae. By comparing the shared and disparate mechanistic bases of morphogenesis and developmental outcomes in the embryos of metazoans (animals), closely related nonmetazoan holozoans, more distantly related dictyostelids, and very distantly related volvocine algae, I conclude, in agreement with Bonner's earlier proposals, that understanding the evolution of multicellular evolution requires knowledge of the inherent forms of diversifying lineages, and that the relevant causative factors extend beyond genes and adaptation to the physics of materials.}, } @article {pmid31370870, year = {2019}, author = {Yeoh, LM and Goodman, CD and Mollard, V and McHugh, E and Lee, VV and Sturm, A and Cozijnsen, A and McFadden, GI and Ralph, SA}, title = {Alternative splicing is required for stage differentiation in malaria parasites.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {151}, pmid = {31370870}, issn = {1474-760X}, mesh = {*Alternative Splicing ; Animals ; Germ Cells/metabolism ; Life Cycle Stages/genetics ; Mice ; Plasmodium berghei/*genetics/growth & development/metabolism ; Transcription, Genetic ; }, abstract = {BACKGROUND: In multicellular organisms, alternative splicing is central to tissue differentiation and identity. Unicellular protists lack multicellular tissue but differentiate into variable cell types during their life cycles. The role of alternative splicing in transitions between cell types and establishing cellular identity is currently unknown in any unicellular organism.

RESULTS: To test whether alternative splicing in unicellular protists plays a role in cellular differentiation, we conduct RNA-seq to compare splicing in female and male sexual stages to asexual intraerythrocytic stages in the rodent malaria parasite Plasmodium berghei. We find extensive changes in alternative splicing between stages and a role for alternative splicing in sexual differentiation. Previously, general gametocyte differentiation was shown to be modulated by specific transcription factors. Here, we show that alternative splicing establishes a subsequent layer of regulation, controlling genes relating to consequent sex-specific differentiation of gametocytes.

CONCLUSIONS: We demonstrate that alternative splicing is reprogrammed during cellular differentiation of a unicellular protist. Disruption of an alternative splicing factor, PbSR-MG, perturbs sex-specific alternative splicing and decreases the ability of the parasites to differentiate into male gametes and oocysts, thereby reducing transmission between vertebrate and insect hosts. Our results reveal alternative splicing as an integral, stage-specific phenomenon in these protists and as a regulator of cellular differentiation that arose early in eukaryotic evolution.}, } @article {pmid31367038, year = {2019}, author = {Olin-Sandoval, V and Yu, JSL and Miller-Fleming, L and Alam, MT and Kamrad, S and Correia-Melo, C and Haas, R and Segal, J and Peña Navarro, DA and Herrera-Dominguez, L and Méndez-Lucio, O and Vowinckel, J and Mülleder, M and Ralser, M}, title = {Lysine harvesting is an antioxidant strategy and triggers underground polyamine metabolism.}, journal = {Nature}, volume = {572}, number = {7768}, pages = {249-253}, pmid = {31367038}, issn = {1476-4687}, support = {200829/WT_/Wellcome Trust/United Kingdom ; FC001134/MRC_/Medical Research Council/United Kingdom ; FC001134/CRUK_/Cancer Research UK/United Kingdom ; W 1224/FWF_/Austrian Science Fund FWF/Austria ; 260809/ERC_/European Research Council/International ; FC001134/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Antioxidants/*metabolism ; Antiporters/metabolism ; Cadaverine/metabolism ; Glutamine/metabolism ; Glutathione/metabolism ; Lysine/*metabolism ; NADP/metabolism ; Organic Cation Transport Proteins/metabolism ; Ornithine Decarboxylase/metabolism ; Oxidants/metabolism ; Polyamines/*metabolism ; Reactive Oxygen Species/metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; }, abstract = {Both single and multicellular organisms depend on anti-stress mechanisms that enable them to deal with sudden changes in the environment, including exposure to heat and oxidants. Central to the stress response are dynamic changes in metabolism, such as the transition from the glycolysis to the pentose phosphate pathway-a conserved first-line response to oxidative insults[1,2]. Here we report a second metabolic adaptation that protects microbial cells in stress situations. The role of the yeast polyamine transporter Tpo1p[3-5] in maintaining oxidant resistance is unknown[6]. However, a proteomic time-course experiment suggests a link to lysine metabolism. We reveal a connection between polyamine and lysine metabolism during stress situations, in the form of a promiscuous enzymatic reaction in which the first enzyme of the polyamine pathway, Spe1p, decarboxylates lysine and forms an alternative polyamine, cadaverine. The reaction proceeds in the presence of extracellular lysine, which is taken up by cells to reach concentrations up to one hundred times higher than those required for growth. Such extensive harvest is not observed for the other amino acids, is dependent on the polyamine pathway and triggers a reprogramming of redox metabolism. As a result, NADPH-which would otherwise be required for lysine biosynthesis-is channelled into glutathione metabolism, leading to a large increase in glutathione concentrations, lower levels of reactive oxygen species and increased oxidant tolerance. Our results show that nutrient uptake occurs not only to enable cell growth, but when the nutrient availability is favourable it also enables cells to reconfigure their metabolism to preventatively mount stress protection.}, } @article {pmid31366234, year = {2019}, author = {Wessely, A and Waltera, A and Reichert, TE and Stöckl, S and Grässel, S and Bauer, RJ}, title = {Induction of ALP and MMP9 activity facilitates invasive behavior in heterogeneous human BMSC and HNSCC 3D spheroids.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {11}, pages = {11884-11893}, pmid = {31366234}, issn = {1530-6860}, mesh = {Adipose Tissue/cytology/metabolism ; Alkaline Phosphatase/*metabolism ; Bone Marrow Cells/cytology/*metabolism ; Carcinoma, Squamous Cell/*metabolism/pathology ; Cell Culture Techniques/methods ; Cell Differentiation ; Cell Movement ; Cells, Cultured ; Enzyme Induction ; Head and Neck Neoplasms/*metabolism/pathology ; Humans ; Matrix Metalloproteinase 9/*metabolism ; Mesenchymal Stem Cells/cytology/*metabolism ; Spheroids, Cellular/*metabolism/pathology ; }, abstract = {Mesenchymal stem cells (MSCs) are multipotent progenitor cells capable of differentiating into adipocytic, osteogenic, chondrogenic, and myogenic lineages. There is growing evidence that MSCs home into the tumor microenvironment attracted by a variety of signals such as chemokines, growth factors, and cytokines. Tumor-homing stem cells may originate from bone marrow-derived MSCs (BMSCs) or adipose tissue-derived MSCs. Recent scientific data suggest that MSCs in combination with tumor cells can either promote or inhibit tumorigenic behavior. In head and neck squamous cell carcinoma (HNSCC), BMSCs are reported to be enriched with a potential negative role. Here, we evaluated the effect of BMSCs from 4 different donors in combination with 4 HNSCC cell lines in a 3-dimensional multicellular spheroid model. Heterogeneous combinations revealed an up-regulation of gene and protein expression of osteogenic markers runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP) together with a substantial secretion of matrix metalloproteinase 9. Moreover, heterogenous BMSC/tumor spheroids showed increased invasion compared with homogenous spheroids in a Boyden chamber invasion assay. Furthermore, inhibition of ALP resulted in a substantially decreased spreading of heterogeneous spheroids on laminin-rich matrix. In summary, our data suggest a prometastatic effect of BMSCs combined with HNSCC.-Wessely, A., Waltera, A., Reichert, T. E., Stöckl, S., Grässel, S., Bauer, R. J. Induction of ALP and MMP9 activity facilitates invasive behavior in heterogeneous human BMSC and HNSCC 3D-spheroids.}, } @article {pmid31347665, year = {2019}, author = {Lu, TM and Kanda, M and Furuya, H and Satoh, N}, title = {Dicyemid Mesozoans: A Unique Parasitic Lifestyle and a Reduced Genome.}, journal = {Genome biology and evolution}, volume = {11}, number = {8}, pages = {2232-2243}, pmid = {31347665}, issn = {1759-6653}, mesh = {Animals ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; *Genome ; Invertebrates/classification/*genetics/growth & development ; Parasites/*genetics ; Phylogeny ; Proteins/*genetics ; Transcriptome ; }, abstract = {Dicyemids, previously called "mesozoans" (intermediates between unicellular protozoans and multicellular metazoans), are an enigmatic animal group. They have a highly simplified adult body, comprising only ∼30 cells, and they have a unique parasitic lifestyle. Recently, dicyemids were shown to be spiralians, with affinities to the Platyhelminthes. In order to understand molecular mechanisms involved in evolution of this odd animal, we sequenced the genome of Dicyema japonicum and a reference transcriptome assembly using mixed-stage samples. The D. japonicum genome features a high proportion of repetitive sequences that account for 49% of the genome. The dicyemid genome is reduced to ∼67.5 Mb with 5,012 protein-coding genes. Only four Hox genes exist in the genome, with no clustering. Gene distribution in KEGG pathways shows that D. japonicum has fewer genes in most pathways. Instead of eliminating entire critical metabolic pathways, parasitic lineages likely simplify pathways by eliminating pathway-specific genes, while genes with fundamental functions may be retained in multiple pathways. In principle, parasites can stand to lose genes that are unnecessary, in order to conserve energy. However, whether retained genes in incomplete pathways serve intermediate functions and how parasites overcome the physiological needs served by lost genes, remain to be investigated in future studies.}, } @article {pmid31339482, year = {2019}, author = {Guo, JS and Zhang, Z and Qiao, M and Yu, ZF}, title = {Phalangispora sinensis sp. nov. from Yunnan, China and two new members of Wiesneriomycetaceae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {10}, pages = {3217-3223}, doi = {10.1099/ijsem.0.003612}, pmid = {31339482}, issn = {1466-5034}, mesh = {Ascomycota/*classification/isolation & purification ; China ; DNA, Fungal/genetics ; Mycological Typing Techniques ; *Phylogeny ; Sequence Analysis, DNA ; Spores, Fungal ; *Water Microbiology ; }, abstract = {Phalangispora sinensis, an aquatic hyphomycete collected from south-western PR China, is described as a new species. This new species is characterized by having multicellular branched conidia composed of a curved main axis and one or two laterals, with the laterals arising from the third or fourth cell of the base of the main axis. Combined analyses of the LSU, SSU, RPB2 and TEF1 gene sequence data revealed that Phalangispora and another aquatic hyphomycete genus, Setosynnema, belonged to Wiesneriomycetaceae, Tubeufiales, Dothideomycetes, Ascomycota.}, } @article {pmid31325911, year = {2019}, author = {Perez-Lamarque, B and Morlon, H}, title = {Characterizing symbiont inheritance during host-microbiota evolution: Application to the great apes gut microbiota.}, journal = {Molecular ecology resources}, volume = {19}, number = {6}, pages = {1659-1671}, doi = {10.1111/1755-0998.13063}, pmid = {31325911}, issn = {1755-0998}, support = {Programme Bettencourt//Ecole Doctorale FIRE/ ; //Ecole normale supérieure/ ; //Centre National de la Recherche Scientifique/ ; PANDA/ERC_/European Research Council/International ; /ERC_/European Research Council/International ; //École Normale Supérieure/ ; }, mesh = {Animals ; Bacteria/genetics ; DNA Barcoding, Taxonomic/methods ; Disease Transmission, Infectious ; Evolution, Molecular ; Gastrointestinal Microbiome/*genetics ; Hominidae/*microbiology ; Infectious Disease Transmission, Vertical ; Microbiota/*genetics ; Phylogeny ; Symbiosis/*genetics ; }, abstract = {Microbiota play a central role in the functioning of multicellular life, yet understanding their inheritance during host evolutionary history remains an important challenge. Symbiotic microorganisms are either acquired from the environment during the life of the host (i.e. environmental acquisition), transmitted across generations with a faithful association with their hosts (i.e. strict vertical transmission), or transmitted with occasional host switches (i.e. vertical transmission with horizontal switches). These different modes of inheritance affect microbes' diversification, which at the two extremes can be independent from that of their associated host or follow host diversification. The few existing quantitative tools for investigating the inheritance of symbiotic organisms rely on cophylogenetic approaches, which require knowledge of both host and symbiont phylogenies, and are therefore often not well adapted to DNA metabarcoding microbial data. Here, we develop a model-based framework for identifying vertically transmitted microbial taxa. We consider a model for the evolution of microbial sequences on a fixed host phylogeny that includes vertical transmission and horizontal host switches. This model allows estimating the number of host switches and testing for strict vertical transmission and independent evolution. We test our approach using simulations. Finally, we illustrate our framework on gut microbiota high-throughput sequencing data of the family Hominidae and identify several microbial taxonomic units, including fibrolytic bacteria involved in carbohydrate digestion, that tend to be vertically transmitted.}, } @article {pmid31311656, year = {2019}, author = {Smith, EA and Hodges, HC}, title = {The Spatial and Genomic Hierarchy of Tumor Ecosystems Revealed by Single-Cell Technologies.}, journal = {Trends in cancer}, volume = {5}, number = {7}, pages = {411-425}, pmid = {31311656}, issn = {2405-8025}, support = {R00 CA187565/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics ; Genetic Predisposition to Disease ; *Genome-Wide Association Study/methods ; *Genomics/methods ; Humans ; Immunomodulation ; Lymphocytes, Tumor-Infiltrating/immunology/metabolism/pathology ; Mutation ; Neoplasms/*genetics/*metabolism/pathology ; Single-Cell Analysis/methods ; *Tumor Microenvironment ; }, abstract = {Many malignancies display heterogeneous features that support cancer progression. Emerging high-resolution methods provide a view of heterogeneity that recognizes the influence of diverse cell types and cell states of the tumor microenvironment. Here we outline a hierarchical organization of tumor heterogeneity from a genomic perspective, summarize the origins of spatially patterned metabolic features, and review recent developments in single-cell and spatially resolved techniques for genome-wide study of multicellular tissues. We also discuss how integrating these approaches can yield new insights into human cancer and emerging immune therapies. Applying these technologies for the analysis of primary tumors, patient-derived xenografts, and in vitro systems holds great promise for understanding the hierarchical structure and environmental influences that underlie tumor ecosystems.}, } @article {pmid31311477, year = {2019}, author = {Boscaro, V and Husnik, F and Vannini, C and Keeling, PJ}, title = {Symbionts of the ciliate Euplotes: diversity, patterns and potential as models for bacteria-eukaryote endosymbioses.}, journal = {Proceedings. Biological sciences}, volume = {286}, number = {1907}, pages = {20190693}, pmid = {31311477}, issn = {1471-2954}, mesh = {Burkholderiaceae/classification/genetics/*physiology ; Euplotes/*microbiology ; Microbiota ; Phylogeny ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/analysis ; *Symbiosis ; }, abstract = {Endosymbioses between bacteria and eukaryotes are enormously important in ecology and evolution, and as such are intensely studied. Despite this, the range of investigated hosts is narrow in the context of the whole eukaryotic tree of life: most of the information pertains to animal hosts, while most of the diversity is found in unicellular protists. A prominent case study is the ciliate Euplotes, which has repeatedly taken up the bacterium Polynucleobacter from the environment, triggering its transformation into obligate endosymbiont. This multiple origin makes the relationship an excellent model to understand recent symbioses, but Euplotes may host bacteria other than Polynucleobacter, and a more detailed knowledge of these additional interactions is needed in order to correctly interpret the system. Here, we present the first systematic survey of Euplotes endosymbionts, adopting a classical as well as a metagenomic approach, and review the state of knowledge. The emerging picture is indeed quite complex, with some Euplotes harbouring rich, stable prokaryotic communities not unlike those of multicellular animals. We provide insights into the distribution, evolution and diversity of these symbionts (including the establishment of six novel bacterial taxa), and outline differences and similarities with the most well-understood group of eukaryotic hosts: insects.}, } @article {pmid31310602, year = {2019}, author = {Karolak, A and Poonja, S and Rejniak, KA}, title = {Morphophenotypic classification of tumor organoids as an indicator of drug exposure and penetration potential.}, journal = {PLoS computational biology}, volume = {15}, number = {7}, pages = {e1007214}, pmid = {31310602}, issn = {1553-7358}, support = {U01 CA202229/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents/administration & dosage/pharmacokinetics ; Computational Biology ; Computer Simulation ; Disease Progression ; Drug Screening Assays, Antitumor ; Humans ; Imaging, Three-Dimensional ; Models, Biological ; Neoplasms/*drug therapy/metabolism/*pathology ; Organoids/*drug effects/metabolism/*pathology ; Phenotype ; Surface Properties ; Tumor Cells, Cultured ; Tumor Microenvironment/drug effects/physiology ; }, abstract = {The dynamics of tumor progression is driven by multiple factors, which can be exogenous to the tumor (microenvironment) or intrinsic (genetic, epigenetic or due to intercellular interactions). While tumor heterogeneity has been extensively studied on the level of cell genetic profiles or cellular composition, tumor morphological diversity has not been given as much attention. The limited analysis of tumor morphophenotypes may be attributed to the lack of accurate models, both experimental and computational, capable of capturing changes in tumor morphology with fine levels of spatial detail. Using a three-dimensional, agent-based, lattice-free computational model, we generated a library of multicellular tumor organoids, the experimental analogues of in vivo tumors. By varying three biologically relevant parameters-cell radius, cell division age and cell sensitivity to contact inhibition, we showed that tumor organoids with similar growth dynamics can express distinct morphologies and possess diverse cellular compositions. Taking advantage of the high-resolution of computational modeling, we applied the quantitative measures of compactness and accessible surface area, concepts that originated from the structural biology of proteins. Based on these analyses, we demonstrated that tumor organoids with similar sizes may differ in features associated with drug effectiveness, such as potential exposure to the drug or the extent of drug penetration. Both these characteristics might lead to major differences in tumor organoid's response to therapy. This indicates that therapeutic protocols should not be based solely on tumor size, but take into account additional tumor features, such as their morphology or cellular packing density.}, } @article {pmid31302471, year = {2019}, author = {Newman, SA}, title = {Inherency and homomorphy in the evolution of development.}, journal = {Current opinion in genetics & development}, volume = {57}, number = {}, pages = {1-8}, doi = {10.1016/j.gde.2019.05.006}, pmid = {31302471}, issn = {1879-0380}, mesh = {Animals ; *Biological Evolution ; Body Patterning/*genetics/physiology ; Embryonic Development/*genetics/physiology ; Gene Expression Regulation, Developmental/genetics ; Physical Phenomena ; }, abstract = {Organismal development occurs when expression of certain genes leads to the mobilization of physical forces and effects that shape and pattern multicellular clusters. All materials exhibit preferred forms, but the inherent morphological motifs of some, such as liquids and crystalline solids are well-characterized. Recent work has shown that the origin of the animals (Metazoa) was accompanied by the acquisition by their developing tissues of liquid-like and liquid-crystalline properties. This and the novel capacity to produce stiff internal substrata (basal laminae) set these organisms apart from their closest relatives by the propensity (predictable from their material nature) to form complex bodies and organs. Once functional forms became established, however, they were susceptible to further genetic change as well as partial or full supplanting of original physical determinants by different ones. This results in the increasingly recognized phenomenon of homomorphy, the presence of the same structure in descendent organisms, brought about by transformed developmental mechanisms.}, } @article {pmid31295970, year = {2019}, author = {Joukov, V and De Nicolo, A}, title = {The Centrosome and the Primary Cilium: The Yin and Yang of a Hybrid Organelle.}, journal = {Cells}, volume = {8}, number = {7}, pages = {}, pmid = {31295970}, issn = {2073-4409}, mesh = {Animals ; Cell Cycle ; Cell Differentiation ; Centrioles/metabolism/physiology ; Centrosome/*metabolism/*physiology ; Cilia/genetics/*metabolism ; Humans ; Microtubule-Organizing Center/physiology ; Microtubules/physiology ; Mitosis/genetics ; Organelles/metabolism/physiology ; }, abstract = {Centrosomes and primary cilia are usually considered as distinct organelles, although both are assembled with the same evolutionary conserved, microtubule-based templates, the centrioles. Centrosomes serve as major microtubule- and actin cytoskeleton-organizing centers and are involved in a variety of intracellular processes, whereas primary cilia receive and transduce environmental signals to elicit cellular and organismal responses. Understanding the functional relationship between centrosomes and primary cilia is important because defects in both structures have been implicated in various diseases, including cancer. Here, we discuss evidence that the animal centrosome evolved, with the transition to complex multicellularity, as a hybrid organelle comprised of the two distinct, but intertwined, structural-functional modules: the centriole/primary cilium module and the pericentriolar material/centrosome module. The evolution of the former module may have been caused by the expanding cellular diversification and intercommunication, whereas that of the latter module may have been driven by the increasing complexity of mitosis and the requirement for maintaining cell polarity, individuation, and adhesion. Through its unique ability to serve both as a plasma membrane-associated primary cilium organizer and a juxtanuclear microtubule-organizing center, the animal centrosome has become an ideal integrator of extracellular and intracellular signals with the cytoskeleton and a switch between the non-cell autonomous and the cell-autonomous signaling modes. In light of this hypothesis, we discuss centrosome dynamics during cell proliferation, migration, and differentiation and propose a model of centrosome-driven microtubule assembly in mitotic and interphase cells. In addition, we outline the evolutionary benefits of the animal centrosome and highlight the hierarchy and modularity of the centrosome biogenesis networks.}, } @article {pmid31294230, year = {2018}, author = {Grishkan, I}, title = {Spatiotemporal variations in soil cultivable mycobiota at the Arava desert (Israel) along latitudinal and elevational gradients.}, journal = {AIMS microbiology}, volume = {4}, number = {3}, pages = {502-521}, pmid = {31294230}, issn = {2471-1888}, abstract = {Regional, local, and seasonal distribution of soil culturable microfungi in the Arava Valley, Israel, was examined along altitudinal and latitudinal gradients. A total of 198 species from 86 genera were isolated using the soil dilution plate method. Melanin-containing species with large multi-cellular spores dominated the majority of microfungal communities, while species with picnidial fruit bodies mostly prevailed in the northern part of the Arava Valley located at 190 m below sea level. Aspergilli (mainly Aspergillus fumigatus) and teleomorphic ascomycetes comprised the basic part of thermotolerant mycobiota obtained at 37 °C. The soil at the northern part of the desert held the highest number of microfungal isolates and, at the same time, was characterized by significantly lower species richness. The open sun-exposed localities harbored a significantly higher number of species than the localities under shrub canopies. Isolate density displayed the opposite trend and was significantly lower in the open than in shrub localities. The mycobiota characteristics such as species composition, contribution of major groupings to mycobiota structure, diversity level, and isolate density showed significant correlations with measured edaphic parameters-organic matter content, water content, pH, and especially, with electrical conductivity. Among the environmental aspects, locality position along altitudinal and latitudinal gradients accompanied by locality type (open sun-exposed or under shrubs), strongly influenced the community's characteristics, thus demonstrating the effect of the unique altitudinal position of the northern part of the Arava Valley as well as the ability of microfungal communities to be sensitive to the microscale environmental variability.}, } @article {pmid31291955, year = {2019}, author = {Yang, YJ and Singh, RP and Lan, X and Zhang, CS and Sheng, DH and Li, YQ}, title = {Whole transcriptome analysis and gene deletion to understand the chloramphenicol resistance mechanism and develop a screening method for homologous recombination in Myxococcus xanthus.}, journal = {Microbial cell factories}, volume = {18}, number = {1}, pages = {123}, pmid = {31291955}, issn = {1475-2859}, support = {ASTIP-TRIC07//Agricultural Science and Technology Innovation Program of China/ ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Chloramphenicol Resistance/*genetics ; *Gene Deletion ; Gene Editing ; *Gene Expression Profiling ; *Homologous Recombination ; Multigene Family ; Myxococcus xanthus/drug effects/*genetics ; Transcriptome ; }, abstract = {BACKGROUND: Myxococcus xanthus DK1622 is a model system for studying multicellular development, predation, cellular differentiation, and evolution. Furthermore, it is a rich source of novel secondary metabolites and is widely used as heterologous expression host of exogenous biosynthetic gene clusters. For decades, genetic modification of M. xanthus DK1622 has mainly relied on kanamycin and tetracycline selection systems.

RESULTS: Here, we introduce an alternative selection system based on chloramphenicol (Cm) to broaden the spectrum of available molecular tools. A chloramphenicol-resistant growth phase and a chloramphenicol-susceptible growth phase before and after chloramphenicol-induction were prepared, and later sequenced to identify specific genes related to chloramphenicol-repercussion and drug-resistance. A total of 481 differentially expressed genes were revealed in chloramphenicol-resistant Cm5_36h and 1920 differentially expressed genes in chloramphenicol-dormant Cm_8h. Moreover, the gene expression profile in the chloramphenicol-dormant strain Cm_8h was quite different from that of Cm5_36 which had completely adapted to Cm, and 1513 differentially expression genes were identified between these two phenotypes. Besides upregulated acetyltransferases, several transporter encoding genes, including ABC transporters, major facilitator superfamily transporters (MFS), resistance-nodulation-cell division (RND) super family transporters and multidrug and toxic compound extrusion family transporters (MATE) were found to be involved in Cm resistance. After the knockout of the most highly upregulated MXAN_2566 MFS family gene, mutant strain DK-2566 was proved to be sensitive to Cm by measuring the growth curve in the Cm-added condition. A plasmid with a Cm resistance marker was constructed and integrated into chromosomes via homologous recombination and Cm screening. The integration efficiency was about 20% at different concentrations of Cm.

CONCLUSIONS: This study provides a new antibiotic-based selection system, and will help to understand antibiotic resistance mechanisms in M. xanthus DK1622.}, } @article {pmid31286803, year = {2019}, author = {Rezaei-Lotfi, S and Hunter, N and Farahani, RM}, title = {Coupled cycling programs multicellular self-organization of neural progenitors.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {18}, number = {17}, pages = {2040-2054}, pmid = {31286803}, issn = {1551-4005}, support = {R01 DE015272/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Humans ; Models, Theoretical ; Morphogenesis/*genetics ; Neural Stem Cells/*metabolism/pathology ; Neurogenesis/genetics ; Neurons/*metabolism/pathology ; beta Catenin/*genetics ; }, abstract = {Self-organization is central to the morphogenesis of multicellular organisms. However, the molecular platform that coordinates the robust emergence of complex morphological patterns from local interactions between cells remains unresolved. Here we demonstrate that neural self- organization is driven by coupled cycling of progenitor cells. In a coupled cycling mode, intercellular contacts relay extrinsic cues to override the intrinsic cycling rhythm of an individual cell and synchronize the population. The stringency of coupling and hence the synchronicity of the population is programmed by recruitment of a key coupler, β-catenin, into junctional complexes. As such, multicellular self-organization is driven by the same basic mathematical principle that governs synchronized behavior of macro-scale biological systems as diverse as the synchronized chirping of crickets, flashing of fireflies and schooling of fish; that is synchronization by coupling. It is proposed that coupled cycling foreshadows a fundamental adaptive change that facilitated evolution and diversification of multicellular life forms.}, } @article {pmid31285576, year = {2019}, author = {Staps, M and van Gestel, J and Tarnita, CE}, title = {Emergence of diverse life cycles and life histories at the origin of multicellularity.}, journal = {Nature ecology & evolution}, volume = {3}, number = {8}, pages = {1197-1205}, pmid = {31285576}, issn = {2397-334X}, mesh = {Animals ; *Biological Evolution ; }, abstract = {The evolution of multicellularity has given rise to a remarkable diversity of multicellular life cycles and life histories. Whereas some multicellular organisms are long-lived, grow through cell division, and repeatedly release single-celled propagules (for example, animals), others are short-lived, form by aggregation, and propagate only once, by generating large numbers of solitary cells (for example, cellular slime moulds). There are no systematic studies that explore how diverse multicellular life cycles can come about. Here, we focus on the origin of multicellularity and develop a mechanistic model to examine the primitive life cycles that emerge from a unicellular ancestor when an ancestral gene is co-opted for cell adhesion. Diverse life cycles readily emerge, depending on ecological conditions, group-forming mechanism, and ancestral constraints. Among these life cycles, we recapitulate both extremes of long-lived groups that propagate continuously and short-lived groups that propagate only once, with the latter type of life cycle being particularly favoured when groups can form by aggregation. Our results show how diverse life cycles and life histories can easily emerge at the origin of multicellularity, shaped by ancestral constraints and ecological conditions. Beyond multicellularity, this finding has similar implications for other major transitions, such as the evolution of sociality.}, } @article {pmid31278352, year = {2019}, author = {Gründger, F and Carrier, V and Svenning, MM and Panieri, G and Vonnahme, TR and Klasek, S and Niemann, H}, title = {Methane-fuelled biofilms predominantly composed of methanotrophic ANME-1 in Arctic gas hydrate-related sediments.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {9725}, pmid = {31278352}, issn = {2045-2322}, mesh = {Biofilms ; DNA, Ribosomal/genetics ; Deltaproteobacteria/*classification/genetics/physiology ; Geologic Sediments/*microbiology ; High-Throughput Nucleotide Sequencing ; Methane/*metabolism ; Microscopy, Confocal ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA ; }, abstract = {Sedimentary biofilms comprising microbial communities mediating the anaerobic oxidation of methane are rare. Here, we describe two biofilm communities discovered in sediment cores recovered from Arctic cold seep sites (gas hydrate pingos) in the north-western Barents Sea, characterized by steady methane fluxes. We found macroscopically visible biofilms in pockets in the sediment matrix at the depth of the sulphate-methane-transition zone. 16S rRNA gene surveys revealed that the microbial community in one of the two biofilms comprised exclusively of putative anaerobic methanotrophic archaea of which ANME-1 was the sole archaeal taxon. The bacterial community consisted of relatives of sulphate-reducing bacteria (SRB) belonging to uncultured Desulfobacteraceae clustering into SEEP-SRB1 (i.e. the typical SRB associated to ANME-1), and members of the atribacterial JS1 clade. Confocal laser scanning microscopy demonstrates that this biofilm is composed of multicellular strands and patches of ANME-1 that are loosely associated with SRB cells, but not tightly connected in aggregates. Our discovery of methanotrophic biofilms in sediment pockets closely associated with methane seeps constitutes a hitherto overlooked and potentially widespread sink for methane and sulphate in marine sediments.}, } @article {pmid31267819, year = {2019}, author = {Etxebeste, O and Otamendi, A and Garzia, A and Espeso, EA and Cortese, MS}, title = {Rewiring of transcriptional networks as a major event leading to the diversity of asexual multicellularity in fungi.}, journal = {Critical reviews in microbiology}, volume = {45}, number = {5-6}, pages = {548-563}, doi = {10.1080/1040841X.2019.1630359}, pmid = {31267819}, issn = {1549-7828}, mesh = {Fungal Proteins/genetics/*metabolism ; Fungi/genetics/*growth & development/physiology ; *Gene Expression Regulation, Fungal ; Gene Regulatory Networks ; Reproduction, Asexual ; Spores, Fungal/genetics/growth & development/metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Complex multicellularity (CM) is characterized by the generation of three-dimensional structures that follow a genetically controlled program. CM emerged at least five times in evolution, one of them in fungi. There are two types of CM programs in fungi, leading, respectively, to the formation of sexual or asexual spores. Asexual spores foment the spread of mycoses, as they are the main vehicle for dispersion. In spite of this key dependence, there is great morphological diversity of asexual multicellular structures in fungi. To advance the understanding of the mechanisms that control initiation and progression of asexual CM and how they can lead to such a remarkable morphological diversification, we studied 503 fungal proteomes, representing all phyla and subphyla, and most known classes. Conservation analyses of 33 regulators of asexual development suggest stepwise emergence of transcription factors. While velvet proteins constitute one of the most ancient systems, the central regulator BrlA emerged late in evolution (with the class Eurotiomycetes). Some factors, such as MoConX4, seem to be species-specific. These observations suggest that the emergence and evolution of transcriptional regulators rewire transcriptional networks. This process could reach the species level, resulting in a vast diversity of morphologies.}, } @article {pmid31254720, year = {2019}, author = {Falz, AL and Müller-Schüssele, SJ}, title = {Physcomitrella as a model system for plant cell biology and organelle-organelle communication.}, journal = {Current opinion in plant biology}, volume = {52}, number = {}, pages = {7-13}, doi = {10.1016/j.pbi.2019.05.007}, pmid = {31254720}, issn = {1879-0356}, mesh = {*Bryopsida ; Genomics ; Models, Biological ; Organelles ; Plant Cells ; }, abstract = {In multicellular eukaryotic cells, metabolism and growth are sustained by the cooperative functioning of organelles in combination with cell-to-cell communication at the organism level. In land plants, multiple strategies have evolved to adapt to life outside water. As basal land plant, the moss Physcomitrella patens is used for comparative genomics, allowing to study lineage-specific features, as well as to track the evolution of fundamental parameters of plant cell organisation and physiology. P. patens is a versatile model for cell biology research, especially to investigate adaptive growth, stress biology as well as organelle dynamics and interactions. Recent advances include the use of genetically encoded biosensors for in vivo imaging of physiological parameters.}, } @article {pmid31246972, year = {2019}, author = {Aufrecht, JA and Fowlkes, JD and Bible, AN and Morrell-Falvey, J and Doktycz, MJ and Retterer, ST}, title = {Pore-scale hydrodynamics influence the spatial evolution of bacterial biofilms in a microfluidic porous network.}, journal = {PloS one}, volume = {14}, number = {6}, pages = {e0218316}, pmid = {31246972}, issn = {1932-6203}, mesh = {*Biofilms ; Biopolymers/metabolism ; Fluorescence ; *Hydrodynamics ; *Microfluidics/instrumentation ; Mutation/genetics ; Pantoea/growth & development/*physiology ; Porosity ; Pressure ; Time Factors ; }, abstract = {Bacteria occupy heterogeneous environments, attaching and growing within pores in materials, living hosts, and matrices like soil. Systems that permit high-resolution visualization of dynamic bacterial processes within the physical confines of a realistic and tractable porous media environment are rare. Here we use microfluidics to replicate the grain shape and packing density of natural sands in a 2D platform to study the flow-induced spatial evolution of bacterial biofilms underground. We discover that initial bacterial dispersal and grain attachment is influenced by bacterial transport across pore space velocity gradients, a phenomenon otherwise known as rheotaxis. We find that gravity-driven flow conditions activate different bacterial cell-clustering phenotypes depending on the strain's ability to product extracellular polymeric substances (EPS). A wildtype, biofilm-producing bacteria formed compact, multicellular patches while an EPS-defective mutant displayed a linked-cell phenotype in the presence of flow. These phenotypes subsequently influenced the overall spatial distribution of cells across the porous media network as colonies grew and altered the fluid dynamics of their microenvironment.}, } @article {pmid31242614, year = {2019}, author = {Dean, M and Jin, V and Bergsten, TM and Austin, JR and Lantvit, DD and Russo, A and Burdette, JE}, title = {Loss of PTEN in Fallopian Tube Epithelium Results in Multicellular Tumor Spheroid Formation and Metastasis to the Ovary.}, journal = {Cancers}, volume = {11}, number = {6}, pages = {}, pmid = {31242614}, issn = {2072-6694}, support = {R01 CA240301/CA/NCI NIH HHS/United States ; UH3 ES029073/ES/NIEHS NIH HHS/United States ; 543296//Ovarian Cancer Research Alliance/ ; OC130046//U.S. Department of Defense/ ; }, abstract = {High-grade serous ovarian cancer (HGSOC) can originate in the fallopian tube and then spread to the ovary. Our objective was to evaluate the role of multicellular tumor spheroids (MTS) in ovarian metastasis. By testing a panel of murine oviductal epithelial (MOE) cells with genetic alterations mimicking those seen in HGSOC, we found that loss of PTEN allowed MTS formation under ultra-low adhesion conditions. Confirming these results in vivo, MTS-like structures were observed in the oviducts of PAX8[Cre/+] PTEN[flox/flox] mice. MOE PTEN[shRNA] cells could incorporate up to 25% wild type cells into MTS, while higher percentages of wild type cells resulted in a loss of MTS formation. MTS formation allowed MOE PTEN[shRNA] cells to survive better under ultra-low adhesion conditions than control cells. MTS also attached to the ovarian stroma, as would be exposed during ovulation. Interestingly, MTS more robustly cleared monolayers of murine ovarian surface epithelia than murine ovarian fibroblasts. When xenografted into the ovarian bursa, OVCAR8 MTS were able to form tumors in the ovary at a similar rate as an equal number of OVCAR8 cells grown on traditional cell culture plastic. In conclusion, loss of a single gene (PTEN) allows the fallopian tube epithelia to form MTS, which survive better under ultra-low adhesion conditions, attach to the extracellular matrix exposed during ovulation, and colonize the ovary. These results suggest that MTS may contribute to seeding of the ovary in HGSOC patients.}, } @article {pmid31239554, year = {2019}, author = {Ågren, JA and Davies, NG and Foster, KR}, title = {Enforcement is central to the evolution of cooperation.}, journal = {Nature ecology & evolution}, volume = {3}, number = {7}, pages = {1018-1029}, doi = {10.1038/s41559-019-0907-1}, pmid = {31239554}, issn = {2397-334X}, support = {209397/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; *Cooperative Behavior ; Humans ; Symbiosis ; }, abstract = {Cooperation occurs at all levels of life, from genomes, complex cells and multicellular organisms to societies and mutualisms between species. A major question for evolutionary biology is what these diverse systems have in common. Here, we review the full breadth of cooperative systems and find that they frequently rely on enforcement mechanisms that suppress selfish behaviour. We discuss many examples, including the suppression of transposable elements, uniparental inheritance of mitochondria and plastids, anti-cancer mechanisms, reciprocation and punishment in humans and other vertebrates, policing in eusocial insects and partner choice in mutualisms between species. To address a lack of accompanying theory, we develop a series of evolutionary models that show that the enforcement of cooperation is widely predicted. We argue that enforcement is an underappreciated, and often critical, ingredient for cooperation across all scales of biological organization.}, } @article {pmid31236128, year = {2019}, author = {Robu, A and Mironov, V and Neagu, A}, title = {Using Sacrificial Cell Spheroids for the Bioprinting of Perfusable 3D Tissue and Organ Constructs: A Computational Study.}, journal = {Computational and mathematical methods in medicine}, volume = {2019}, number = {}, pages = {7853586}, pmid = {31236128}, issn = {1748-6718}, mesh = {3T3 Cells ; Algorithms ; Animals ; Bioprinting/*methods ; Carcinoma, Lewis Lung/metabolism ; Computer Simulation ; Humans ; Hydrogels/*chemistry ; Metal Nanoparticles/chemistry ; Mice ; Monte Carlo Method ; Perfusion ; *Printing, Three-Dimensional ; Silicon/chemistry ; Spheroids, Cellular/*cytology ; Tissue Engineering/*methods ; Tissue Scaffolds ; }, abstract = {A long-standing problem in tissue engineering is the biofabrication of perfusable tissue constructs that can be readily connected to the patient's vasculature. It was partially solved by three-dimensional (3D) printing of sacrificial material (e.g., hydrogel) strands: upon incorporation in another cell-laden hydrogel, the strands were removed, leaving behind perfusable channels. Their complexity, however, did not match that of the native vasculature. Here, we propose to use multicellular spheroids as a sacrificial material and investigate their potential benefits in the context of 3D bioprinting of cell aggregates and/or cell-laden hydrogels. Our study is based on computer simulations of postprinting cellular rearrangements. The computational model of the biological system is built on a cubic lattice, whereas its evolution is simulated using the Metropolis Monte Carlo algorithm. The simulations describe structural changes in three types of tissue constructs: a tube made of a single cell type, a tube made of two cell types, and a cell-laden hydrogel slab that incorporates a branching tube. In all three constructs, the lumen is obtained after the elimination of the sacrificial cell population. Our study suggests that sacrificial cell spheroids (sacrospheres) enable one to print tissue constructs outfitted with a finer and more complex network of channels than the ones obtained so far. Moreover, cellular interactions might give rise to a tissue microarchitecture that lies beyond the bioprinter's resolution. Although more expensive than inert materials, sacrificial cells have the potential to bring further progress towards the biofabrication of fully vascularized tissue substitutes.}, } @article {pmid31227860, year = {2019}, author = {Tian, L and Zhang, B and Zhang, J and Zhang, T and Cai, Y and Qin, H and Metzner, W and Pan, Y}, title = {A magnetic compass guides the direction of foraging in a bat.}, journal = {Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology}, volume = {205}, number = {4}, pages = {619-627}, pmid = {31227860}, issn = {1432-1351}, mesh = {Animals ; Behavior, Animal/*physiology ; Chiroptera/*physiology ; Cues ; *Magnetic Fields ; Orientation, Spatial/*physiology ; }, abstract = {Previously, two studies have provided evidence that bats can use magnetic field cues for homing or roosting. For insectivorous bats, it is well established that foraging represents one of the most fundamental behaviors in animals relies on their ability to echolocate. Whether echolocating bats can also use magnetic cues during foraging remains unknown, however. Here, we tested the orientation behavior of Chinese noctules (Nyctalus plancyi) during foraging in a plus-shaped, 4-channel apparatus under different magnetic field conditions. To minimize the effects of spatial memory on orientation from repeated experiments, naïve bats were tested only once in each experimental condition. As expected, under geomagnetic field and a food resource offered conditions, the bats significantly preferred to enter the channel containing food, indicating that they primarily relied on direct sensory signals unrelated to magnetic cues. In contrast, when we offered food simultaneously in all four channels and minimized any differences in all other sensory signals available, the bats exhibited a clear directional preference to forage along the magnetic field direction under either geomagnetic field or a magnetic field in which the horizontal component was rotated by 90°. Our study offers a novel evidence for the importance of a geomagnetic field during foraging.}, } @article {pmid31217565, year = {2019}, author = {Patel, DS and Xu, N and Lu, H}, title = {Digging deeper: methodologies for high-content phenotyping in Caenorhabditis elegans.}, journal = {Lab animal}, volume = {48}, number = {7}, pages = {207-216}, pmid = {31217565}, issn = {1548-4475}, support = {R21 EB021676/EB/NIBIB NIH HHS/United States ; R21 EB020424/EB/NIBIB NIH HHS/United States ; R01 NS096581/NS/NINDS NIH HHS/United States ; R01 AG056436/AG/NIA NIH HHS/United States ; R21 DC015652/DC/NIDCD NIH HHS/United States ; R01 GM088333/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*genetics ; *Genetic Techniques/instrumentation ; Laboratory Animal Science/instrumentation/*methods ; *Phenotype ; }, abstract = {Deep phenotyping is an emerging conceptual paradigm and experimental approach aimed at measuring and linking many aspects of a phenotype to understand its underlying biology. To date, deep phenotyping has been applied mostly in cultured cells and used less in multicellular organisms. However, in the past decade, it has increasingly been recognized that deep phenotyping could lead to a better understanding of how genetics, environment and stochasticity affect the development, physiology and behavior of an organism. The nematode Caenorhabditis elegans is an invaluable model system for studying how genes affect a phenotypic trait, and new technologies have taken advantage of the worm's physical attributes to increase the throughput and informational content of experiments. Coupling of these technical advancements with computational and analytical tools has enabled a boom in deep-phenotyping studies of C. elegans. In this Review, we highlight how these new technologies and tools are digging into the biological origins of complex, multidimensional phenotypes.}, } @article {pmid31214991, year = {2019}, author = {Muras, V and Toulouse, C and Fritz, G and Steuber, J}, title = {Respiratory Membrane Protein Complexes Convert Chemical Energy.}, journal = {Sub-cellular biochemistry}, volume = {92}, number = {}, pages = {301-335}, doi = {10.1007/978-3-030-18768-2_10}, pmid = {31214991}, issn = {0306-0225}, mesh = {Archaea/cytology/enzymology/*metabolism ; Bacteria/cytology/enzymology/*metabolism ; Cell Membrane/*metabolism ; *Electron Transport ; *Energy Metabolism ; Membrane Proteins/*chemistry/*metabolism ; }, abstract = {The invention of a biological membrane which is used as energy storage system to drive the metabolism of a primordial, unicellular organism represents a key event in the evolution of life. The innovative, underlying principle of this key event is respiration. In respiration, a lipid bilayer with insulating properties is chosen as the site for catalysis of an exergonic redox reaction converting substrates offered from the environment, using the liberated Gibbs free energy (ΔG) for the build-up of an electrochemical H[+] (proton motive force, PMF) or Na[+] gradient (sodium motive force, SMF) across the lipid bilayer. Very frequently , several redox reactions are performed in a consecutive manner, with the first reaction delivering a product which is used as substrate for the second redox reaction, resulting in a respiratory chain. From today's perspective, the (mostly) unicellular bacteria and archaea seem to be much simpler and less evolved when compared to multicellular eukaryotes. However, they are overwhelmingly complex with regard to the various respiratory chains which permit survival in very different habitats of our planet, utilizing a plethora of substances to drive metabolism. This includes nitrogen, sulfur and carbon compounds which are oxidized or reduced by specialized, respiratory enzymes of bacteria and archaea which lie at the heart of the geochemical N, S and C-cycles. This chapter gives an overview of general principles of microbial respiration considering thermodynamic aspects, chemical reactions and kinetic restraints. The respiratory chains of Escherichia coli and Vibrio cholerae are discussed as models for PMF- versus SMF-generating processes, respectively. We introduce main redox cofactors of microbial respiratory enzymes, and the concept of intra-and interelectron transfer. Since oxygen is an electron acceptor used by many respiratory chains, the formation and removal of toxic oxygen radicals is described. Promising directions of future research are respiratory enzymes as novel bacterial targets, and biotechnological applications relying on respiratory complexes.}, } @article {pmid31212208, year = {2019}, author = {Masuyama, N and Mori, H and Yachie, N}, title = {DNA barcodes evolve for high-resolution cell lineage tracing.}, journal = {Current opinion in chemical biology}, volume = {52}, number = {}, pages = {63-71}, doi = {10.1016/j.cbpa.2019.05.014}, pmid = {31212208}, issn = {1879-0402}, mesh = {Animals ; Biomarkers ; *Cell Lineage ; Clustered Regularly Interspaced Short Palindromic Repeats ; *DNA Barcoding, Taxonomic ; Evolution, Molecular ; Humans ; Mutation ; Single-Cell Analysis ; }, abstract = {Mammalian development involves continuous dynamic processes in which cells propagate, differentiate, orchestrate, and decease to produce high-order functions. Although accurate cell lineage information can provide a strong foundation to understand such complex processes, the cell lineages involved in development of the whole mammalian body remain largely unclear, except for in early embryogenesis, which is observable under a microscope. With CRISPR genome editing, the concept of 'evolving DNA barcodes' has rapidly emerged for large-scale, high-resolution cell lineage tracing, where cell-embedded DNA barcodes continuously accumulate random mutations that are inherited from mother to daughter cells. Similar to evolutionary tree reconstruction using species' DNA sequences, cell lineages can be reconstructed using shared mutation patterns in the DNA barcodes identified using massively parallel sequencing. The dramatic developments of single-cell and imaging technologies have enabled analyses of the molecular and spatial architecture of heterogeneous cells. The evolving DNA barcodes can also consolidate this information on a reconstructed cell lineage tree and accelerate our understanding of multicellular organisms.}, } @article {pmid31209997, year = {2019}, author = {Bonner, JT}, title = {The evolution of evolution.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {8}, pages = {301-306}, doi = {10.1002/jez.b.22859}, pmid = {31209997}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; Evolution, Molecular ; Nervous System ; Origin of Life ; Reproduction ; Selection, Genetic ; }, abstract = {In the past, most biologists, myself included, did not think of evolution as changing over time. The wonders of natural selection were always at hand and went into operation once there was life. However, with a little reflection it becomes obvious that evolution has changed-there has been an evolution of evolution. Evolution can be separated into four phases, or eras, that may or may not overlap. The first era starts with the evolution of life on earth, which led to single cells that multiply asexually. The second era takes advantage of the invention of sexual reproduction as evolution could now gallop forward because of a richer fare of diverse offspring for natural selection. The third era begins with the introduction of multicellularity. In the fourth era there is a radical innovation: the nervous system that arises animals by standard Darwinian selection. This has allowed major rapid changes to proceed, such as language that led to all the rapid progress we call civilization; a true revolution, and one that does not depend on the slow genetic changes of all other standard gene-controlled evolutionary steps.}, } @article {pmid31209289, year = {2019}, author = {Morrissey, EM and Mau, RL and Hayer, M and Liu, XA and Schwartz, E and Dijkstra, P and Koch, BJ and Allen, K and Blazewicz, SJ and Hofmockel, K and Pett-Ridge, J and Hungate, BA}, title = {Evolutionary history constrains microbial traits across environmental variation.}, journal = {Nature ecology & evolution}, volume = {3}, number = {7}, pages = {1064-1069}, doi = {10.1038/s41559-019-0918-y}, pmid = {31209289}, issn = {2397-334X}, mesh = {Biological Evolution ; Carbon ; *Ecosystem ; Nitrogen ; *Soil ; }, abstract = {Organisms influence ecosystems, from element cycling to disturbance regimes, to trophic interactions and to energy partitioning. Microorganisms are part of this influence, and understanding their ecology in nature requires studying the traits of these organisms quantitatively in their natural habitats-a challenging task, but one which new approaches now make possible. Here, we show that growth rate and carbon assimilation rate of soil microorganisms are influenced more by evolutionary history than by climate, even across a broad climatic gradient spanning major temperate life zones, from mixed conifer forest to high-desert grassland. Most of the explained variation (~50% to ~90%) in growth rate and carbon assimilation rate was attributable to differences among taxonomic groups, indicating a strong influence of evolutionary history, and taxonomic groupings were more predictive for organisms responding to resource addition. With added carbon and nitrogen substrates, differences among taxonomic groups explained approximately eightfold more variance in growth rate than did differences in ecosystem type. Taxon-specific growth and carbon assimilation rates were highly intercorrelated across the four ecosystems, constrained by the taxonomic identity of the organisms, such that plasticity driven by environment was limited across ecosystems varying in temperature, precipitation and dominant vegetation. Taken together, our results suggest that, similar to multicellular life, the traits of prokaryotes in their natural habitats are constrained by evolutionary history to a greater degree than environmental variation.}, } @article {pmid31196608, year = {2019}, author = {Pirkmajer, S and Chibalin, AV}, title = {Hormonal regulation of Na[+]-K[+]-ATPase from the evolutionary perspective.}, journal = {Current topics in membranes}, volume = {83}, number = {}, pages = {315-351}, doi = {10.1016/bs.ctm.2019.01.009}, pmid = {31196608}, issn = {1063-5823}, mesh = {Animals ; *Biological Evolution ; Hormones/*metabolism ; Humans ; Sodium-Potassium-Exchanging ATPase/chemistry/*metabolism ; }, abstract = {Na[+]-K[+]-ATPase, an α/β heterodimer, is an ancient enzyme that maintains Na[+] and K[+] gradients, thus preserving cellular ion homeostasis. In multicellular organisms, this basic housekeeping function is integrated to fulfill the needs of specialized organs and preserve whole-body homeostasis. In vertebrates, Na[+]-K[+]-ATPase is essential for many fundamental physiological processes, such as nerve conduction, muscle contraction, nutrient absorption, and urine excretion. During vertebrate evolution, three key developments contributed to diversification and integration of Na[+]-K[+]-ATPase functions. Generation of novel α- and β-subunits led to formation of multiple Na[+]-K[+]-ATPase isoenyzmes with distinct functional characteristics. Development of a complex endocrine system enabled efficient coordination of diverse Na[+]-K[+]-ATPase functions. Emergence of FXYDs, small transmembrane proteins that regulate Na[+]-K[+]-ATPase, opened new ways to modulate its function. FXYDs are a vertebrate innovation and an important site of hormonal action, suggesting they played an especially prominent role in evolving interaction between Na[+]-K[+]-ATPase and the endocrine system in vertebrates.}, } @article {pmid31189954, year = {2019}, author = {Sogabe, S and Hatleberg, WL and Kocot, KM and Say, TE and Stoupin, D and Roper, KE and Fernandez-Valverde, SL and Degnan, SM and Degnan, BM}, title = {Pluripotency and the origin of animal multicellularity.}, journal = {Nature}, volume = {570}, number = {7762}, pages = {519-522}, doi = {10.1038/s41586-019-1290-4}, pmid = {31189954}, issn = {1476-4687}, mesh = {Animals ; Cell Proliferation ; *Cell Transdifferentiation ; Epithelial Cells/cytology/metabolism ; Evolution, Molecular ; *Models, Biological ; *Phylogeny ; Pluripotent Stem Cells/*cytology/metabolism ; Porifera/*cytology/metabolism ; Reproducibility of Results ; Transcriptome ; }, abstract = {A widely held-but rarely tested-hypothesis for the origin of animals is that they evolved from a unicellular ancestor, with an apical cilium surrounded by a microvillar collar, that structurally resembled modern sponge choanocytes and choanoflagellates[1-4]. Here we test this view of animal origins by comparing the transcriptomes, fates and behaviours of the three primary sponge cell types-choanocytes, pluripotent mesenchymal archaeocytes and epithelial pinacocytes-with choanoflagellates and other unicellular holozoans. Unexpectedly, we find that the transcriptome of sponge choanocytes is the least similar to the transcriptomes of choanoflagellates and is significantly enriched in genes unique to either animals or sponges alone. By contrast, pluripotent archaeocytes upregulate genes that control cell proliferation and gene expression, as in other metazoan stem cells and in the proliferating stages of two unicellular holozoans, including a colonial choanoflagellate. Choanocytes in the sponge Amphimedon queenslandica exist in a transient metastable state and readily transdifferentiate into archaeocytes, which can differentiate into a range of other cell types. These sponge cell-type conversions are similar to the temporal cell-state changes that occur in unicellular holozoans[5]. Together, these analyses argue against homology of sponge choanocytes and choanoflagellates, and the view that the first multicellular animals were simple balls of cells with limited capacity to differentiate. Instead, our results are consistent with the first animal cell being able to transition between multiple states in a manner similar to modern transdifferentiating and stem cells.}, } @article {pmid31188035, year = {2019}, author = {Ward, LM and Stamenković, V and Hand, K and Fischer, WW}, title = {Follow the Oxygen: Comparative Histories of Planetary Oxygenation and Opportunities for Aerobic Life.}, journal = {Astrobiology}, volume = {19}, number = {6}, pages = {811-824}, doi = {10.1089/ast.2017.1779}, pmid = {31188035}, issn = {1557-8070}, mesh = {Atmosphere/*analysis/chemistry ; *Cell Respiration ; *Evolution, Planetary ; Exobiology ; Extraterrestrial Environment/*chemistry ; Ice Cover/chemistry ; Jupiter ; Mars ; Oxidation-Reduction ; Oxygen/*chemistry ; Photochemical Processes ; Temperature ; Water/chemistry ; }, abstract = {Aerobic respiration-the reduction of molecular oxygen (O2) coupled to the oxidation of reduced compounds such as organic carbon, ferrous iron, reduced sulfur compounds, or molecular hydrogen while conserving energy to drive cellular processes-is the most widespread and bioenergetically favorable metabolism on Earth today. Aerobic respiration is essential for the development of complex multicellular life; thus the presence of abundant O2 is an important metric for planetary habitability. O2 on Earth is supplied by oxygenic photosynthesis, but it is becoming more widely understood that abiotic processes may supply meaningful amounts of O2 on other worlds. The modern atmosphere and rock record of Mars suggest a history of relatively high O2 as a result of photochemical processes, potentially overlapping with the range of O2 concentrations used by biology. Europa may have accumulated high O2 concentrations in its subsurface ocean due to the radiolysis of water ice at its surface. Recent modeling efforts suggest that coexisting water and O2 may be common on exoplanets, with confirmation from measurements of exoplanet atmospheres potentially coming soon. In all these cases, O2 accumulates through abiotic processes-independent of water-oxidizing photosynthesis. We hypothesize that abiogenic O2 may enhance the habitability of some planetary environments, allowing highly energetic aerobic respiration and potentially even the development of complex multicellular life which depends on it, without the need to first evolve oxygenic photosynthesis. This hypothesis is testable with further exploration and life-detection efforts on O2-rich worlds such as Mars and Europa, and comparison to O2-poor worlds such as Enceladus. This hypothesis further suggests a new dimension to planetary habitability: "Follow the Oxygen," in which environments with opportunities for energy-rich metabolisms such as aerobic respiration are preferentially targeted for investigation and life detection.}, } @article {pmid31187926, year = {2020}, author = {Qian, XX and Santini, CL and Kosta, A and Menguy, N and Le Guenno, H and Zhang, W and Li, J and Chen, YR and Liu, J and Alberto, F and Espinosa, L and Xiao, T and Wu, LF}, title = {Juxtaposed membranes underpin cellular adhesion and display unilateral cell division of multicellular magnetotactic prokaryotes.}, journal = {Environmental microbiology}, volume = {22}, number = {4}, pages = {1481-1494}, doi = {10.1111/1462-2920.14710}, pmid = {31187926}, issn = {1462-2920}, mesh = {Cell Adhesion ; Cell Division ; Cell Membrane ; In Situ Hybridization, Fluorescence ; *Magnetic Phenomena ; Microscopy, Electron, Scanning ; Prokaryotic Cells/*physiology/ultrastructure ; }, abstract = {Multicellular magnetotactic prokaryotes (MMPs) exhibit peculiar coordination of swimming along geomagnetic field lines. Approximately 40-80 cells assemble, with a helical geometry or axisymmetry, into spherical or ellipsoidal MMPs respectively. To contribute to a comprehensive understanding of bacterial multicellularity here we took multiple microscopic approaches to study the diversity, assembly, reproduction and motility of ellipsoidal MMPs. Using correlative fluorescence in situ hybridization and scanning electron microscopy analysis, we found an unexpected diversity in populations of ellipsoidal MMPs in the Mediterranean Sea. The high-pressure freezing/freeze substitution fixation technique allowed us to show, for the first time, that cells adhere via juxtaposed membranes and are held together by a rimming lattice. Fluorescence confocal microscopy and ultrathin section images revealed not only the one-layer hollow three-dimensional architecture, but also periphery-core unilateral constriction of constituent cells and unidirectional binary fission of the ellipsoidal MMPs. This finding suggests the evolution toward MMPs multicellularity via the mechanism of incomplete separation of offspring. Remarkably, thousands of flagellar at the periphery surface of cells underpin the coordinated swimming of MMPs in response to mechanical, chemical, magnetic and optical stimuli, including a magnetotactic photokinesis behaviour. Together these results unveil the unique structure and function property of ellipsoidal MMPs.}, } @article {pmid31185890, year = {2019}, author = {Yamashita, S and Nozaki, H}, title = {Embryogenesis of flattened colonies implies the innovation required for the evolution of spheroidal colonies in volvocine green algae.}, journal = {BMC evolutionary biology}, volume = {19}, number = {1}, pages = {120}, pmid = {31185890}, issn = {1471-2148}, mesh = {Basal Bodies/metabolism ; *Biological Evolution ; Cell Division ; Cell Nucleus/metabolism ; Chlorophyta/classification/cytology/*embryology ; Microtubules/metabolism ; Phylogeny ; Time-Lapse Imaging ; }, abstract = {BACKGROUND: Volvocine algae provide a suitable model for investigation of the evolution of multicellular organisms. Within this group, evolution of the body plan from flattened to spheroidal colonies is thought to have occurred independently in two different lineages, Volvocaceae and Astrephomene. Volvocacean species undergo inversion to form a spheroidal cell layer following successive cell divisions during embryogenesis. During inversion, the daughter protoplasts change their shape and develop acute chloroplast ends (opposite to basal bodies). By contrast, Astrephomene does not undergo inversion; rather, its daughter protoplasts rotate during successive cell divisions to form a spheroidal colony. However, the evolutionary pathways of these cellular events involved in the two tactics for formation of spheroidal colony are unclear, since the embryogenesis of extant volvocine genera with ancestral flattened colonies, such as Gonium and Tetrabaena, has not previously been investigated in detail.

RESULTS: We conducted time-lapse imaging by light microscopy and indirect immunofluorescence microscopy with staining of basal bodies, nuclei, and microtubules to observe embryogenesis in G. pectorale and T. socialis, which form 16-celled or 4-celled flattened colonies, respectively. In G. pectorale, a cup-shaped cell layer of the 16-celled embryo underwent gradual expansion after successive cell divisions, with the apical ends (position of basal bodies) of the square embryo's peripheral protoplasts separated from each other. In T. socialis, on the other hand, there was no apparent expansion of the daughter protoplasts in 4-celled embryos after successive cell divisions, however the two pairs of diagonally opposed daughter protoplasts shifted slightly and flattened after hatching. Neither of these two species exhibited rotation of daughter protoplasts during successive cell divisions as in Astrephomene or the formation of acute chloroplast ends of daughter protoplasts as in volvocacean inversion.

CONCLUSIONS: The present results indicate that the ancestor of Astrephomene might have newly acquired the rotation of daughter protoplasts after it diverged from the ancestor of Gonium, while the ancestor of Volvocaceae might have newly acquired the formation of acute chloroplast ends to complete inversion after divergence from the ancestor of Goniaceae (Gonium and Astrephomene).}, } @article {pmid31185009, year = {2019}, author = {Roy, M and Finley, SD}, title = {Metabolic reprogramming dynamics in tumor spheroids: Insights from a multicellular, multiscale model.}, journal = {PLoS computational biology}, volume = {15}, number = {6}, pages = {e1007053}, pmid = {31185009}, issn = {1553-7358}, mesh = {Cell Line, Tumor ; Cell Proliferation/physiology ; Computational Biology/*methods ; Humans ; Kinetics ; *Models, Biological ; Neoplasms/*metabolism ; Spheroids, Cellular/*metabolism ; }, abstract = {Mathematical modeling provides the predictive ability to understand the metabolic reprogramming and complex pathways that mediate cancer cells' proliferation. We present a mathematical model using a multiscale, multicellular approach to simulate avascular tumor growth, applied to pancreatic cancer. The model spans three distinct spatial and temporal scales. At the extracellular level, reaction diffusion equations describe nutrient concentrations over a span of seconds. At the cellular level, a lattice-based energy driven stochastic approach describes cellular phenomena including adhesion, proliferation, viability and cell state transitions, occurring on the timescale of hours. At the sub-cellular level, we incorporate a detailed kinetic model of intracellular metabolite dynamics on the timescale of minutes, which enables the cells to uptake and excrete metabolites and use the metabolites to generate energy and building blocks for cell growth. This is a particularly novel aspect of the model. Certain defined criteria for the concentrations of intracellular metabolites lead to cancer cell growth, proliferation or death. Overall, we model the evolution of the tumor in both time and space. Starting with a cluster of tumor cells, the model produces an avascular tumor that quantitatively and qualitatively mimics experimental measurements of multicellular tumor spheroids. Through our model simulations, we can investigate the response of individual intracellular species under a metabolic perturbation and investigate how that response contributes to the response of the tumor as a whole. The predicted response of intracellular metabolites under various targeted strategies are difficult to resolve with experimental techniques. Thus, the model can give novel predictions as to the response of the tumor as a whole, identifies potential therapies to impede tumor growth, and predicts the effects of those therapeutic strategies. In particular, the model provides quantitative insight into the dynamic reprogramming of tumor cells at the intracellular level in response to specific metabolic perturbations. Overall, the model is a useful framework to study targeted metabolic strategies for inhibiting tumor growth.}, } @article {pmid31183520, year = {2020}, author = {Chaplain, MAJ and Lorenzi, T and Macfarlane, FR}, title = {Bridging the gap between individual-based and continuum models of growing cell populations.}, journal = {Journal of mathematical biology}, volume = {80}, number = {1-2}, pages = {343-371}, pmid = {31183520}, issn = {1432-1416}, mesh = {Cell Cycle/physiology ; Cell Movement/*physiology ; Cell Proliferation/physiology ; Computer Simulation ; *Models, Biological ; Spatial Analysis ; }, abstract = {Continuum models for the spatial dynamics of growing cell populations have been widely used to investigate the mechanisms underpinning tissue development and tumour invasion. These models consist of nonlinear partial differential equations that describe the evolution of cellular densities in response to pressure gradients generated by population growth. Little prior work has explored the relation between such continuum models and related single-cell-based models. We present here a simple stochastic individual-based model for the spatial dynamics of multicellular systems whereby cells undergo pressure-driven movement and pressure-dependent proliferation. We show that nonlinear partial differential equations commonly used to model the spatial dynamics of growing cell populations can be formally derived from the branching random walk that underlies our discrete model. Moreover, we carry out a systematic comparison between the individual-based model and its continuum counterparts, both in the case of one single cell population and in the case of multiple cell populations with different biophysical properties. The outcomes of our comparative study demonstrate that the results of computational simulations of the individual-based model faithfully mirror the qualitative and quantitative properties of the solutions to the corresponding nonlinear partial differential equations. Ultimately, these results illustrate how the simple rules governing the dynamics of single cells in our individual-based model can lead to the emergence of complex spatial patterns of population growth observed in continuum models.}, } @article {pmid31175621, year = {2020}, author = {Root, A}, title = {Do cells use passwords in cell-state transitions? Is cell signaling sometimes encrypted?.}, journal = {Theory in biosciences = Theorie in den Biowissenschaften}, volume = {139}, number = {1}, pages = {87-93}, pmid = {31175621}, issn = {1611-7530}, mesh = {Algorithms ; Animals ; Autoimmune Diseases/*metabolism ; Biological Evolution ; Biological Phenomena ; Chromatin/metabolism ; Computational Biology ; Entropy ; Environment ; Genome ; Humans ; Immune System ; *Models, Biological ; Neoplasms/*metabolism ; Neurons/metabolism ; Semantics ; *Signal Transduction ; }, abstract = {Organisms must maintain proper regulation including defense and healing. Life-threatening problems may be caused by pathogens or by a multicellular organism's own cells through cancer or autoimmune disorders. Life evolved solutions to these problems that can be conceptualized through the lens of information security, which is a well-developed field in computer science. Here I argue that taking an information security view of cells is not merely semantics, but useful to explain features of signaling, regulation, and defense. An information security perspective also offers a conduit for cross-fertilization of advanced ideas from computer science and the potential for biology to inform computer science. First, I consider whether cells use passwords, i.e., initiation sequences that are required for subsequent signals to have effects, by analyzing the concept of pioneer transcription factors in chromatin regulation and cellular reprogramming. Second, I consider whether cells may encrypt signal transduction cascades. Encryption could benefit cells by making it more difficult for pathogens or oncogenes to hijack cell networks. By using numerous molecules, cells may gain a security advantage in particular against viruses, whose genome sizes are typically under selection pressure. I provide a simple conceptual argument for how cells may perform encryption through posttranslational modifications, complex formation, and chromatin accessibility. I invoke information theory to provide a criterion of an entropy spike to assess whether a signaling cascade has encryption-like features. I discuss how the frequently invoked concept of context dependency may oversimplify more advanced features of cell signaling networks, such as encryption. Therefore, by considering that biochemical networks may be even more complex than commonly realized we may be better able to understand defenses against pathogens and pathologies.}, } @article {pmid31175188, year = {2019}, author = {Kees, ED and Pendleton, AR and Paquete, CM and Arriola, MB and Kane, AL and Kotloski, NJ and Intile, PJ and Gralnick, JA}, title = {Secreted Flavin Cofactors for Anaerobic Respiration of Fumarate and Urocanate by Shewanella oneidensis: Cost and Role.}, journal = {Applied and environmental microbiology}, volume = {85}, number = {16}, pages = {}, pmid = {31175188}, issn = {1098-5336}, mesh = {Anaerobiosis ; Bacterial Proteins/genetics/metabolism ; Electron Transport ; Flavin-Adenine Dinucleotide/metabolism ; Flavins/*metabolism ; Fumarates/*metabolism ; Periplasm ; Shewanella/genetics/growth & development/*metabolism ; Succinate Dehydrogenase/genetics/metabolism ; }, abstract = {Shewanella oneidensis strain MR-1, a facultative anaerobe and model organism for dissimilatory metal reduction, uses a periplasmic flavocytochrome, FccA, both as a terminal fumarate reductase and as a periplasmic electron transfer hub for extracellular respiration of a variety of substrates. It is currently unclear how maturation of FccA and other periplasmic flavoproteins is achieved, specifically in the context of flavin cofactor loading, and the fitness cost of flavin secretion has not been quantified. We demonstrate that deletion of the inner membrane flavin adenine dinucleotide (FAD) exporter Bfe results in a 23% slower growth rate than that of the wild type during fumarate respiration and an 80 to 90% loss in fumarate reductase activity. Exogenous flavin supplementation does not restore FccA activity in a Δbfe mutant unless the gene encoding the periplasmic FAD hydrolase UshA is also deleted. We demonstrate that the small Bfe-independent pool of FccA is sufficient for anaerobic growth with fumarate. Strains lacking Bfe were unable to grow using urocanate as the sole electron acceptor, which relies on the periplasmic flavoprotein UrdA. We show that periplasmic flavoprotein maturation occurs in careful balance with periplasmic FAD hydrolysis, and that the current model for periplasmic flavin cofactor loading must account for a Bfe-independent mechanism for flavin transport. Finally, we determine that the metabolic burden of flavin secretion is not significant during growth with flavin-independent anaerobic electron acceptors. Our work helps frame the physiological motivations that drove evolution of flavin secretion by ShewanellaIMPORTANCEShewanella species are prevalent in marine and aquatic environments, throughout stratified water columns, in mineral-rich sediments, and in association with multicellular marine and aquatic organisms. The diversity of niches shewanellae can occupy are due largely to their respiratory versatility. Shewanella oneidensis is a model organism for dissimilatory metal reduction and can respire a diverse array of organic and inorganic compounds, including dissolved and solid metal oxides. The fumarate reductase FccA is a highly abundant multifunctional periplasmic protein that acts to bridge the periplasm and temporarily store electrons in a variety of respiratory nodes, including metal, nitrate, and dimethyl sulfoxide respiration. However, maturation of this central protein, particularly flavin cofactor acquisition, is poorly understood. Here, we quantify the fitness cost of flavin secretion and describe how free flavins are acquired by FccA and a homologous periplasmic flavoprotein, UrdA.}, } @article {pmid31172192, year = {2019}, author = {St-Georges-Robillard, A and Cahuzac, M and Péant, B and Fleury, H and Lateef, MA and Ricard, A and Sauriol, A and Leblond, F and Mes-Masson, AM and Gervais, T}, title = {Long-term fluorescence hyperspectral imaging of on-chip treated co-culture tumour spheroids to follow clonal evolution.}, journal = {Integrative biology : quantitative biosciences from nano to macro}, volume = {11}, number = {4}, pages = {130-141}, doi = {10.1093/intbio/zyz012}, pmid = {31172192}, issn = {1757-9708}, mesh = {*Cell Culture Techniques ; Cell Line, Tumor ; Cell Proliferation/drug effects ; *Clonal Evolution ; *Coculture Techniques ; Drug Screening Assays, Antitumor ; Female ; Humans ; *Lab-On-A-Chip Devices ; Microfluidics ; Microscopy, Fluorescence/*methods ; Ovarian Neoplasms/drug therapy/pathology ; Spheroids, Cellular/*drug effects ; }, abstract = {Multicellular tumour spheroids are an ideal in vitro tumour model to study clonal heterogeneity and drug resistance in cancer research because different cell types can be mixed at will. However, measuring the individual response of each cell population over time is challenging: current methods are either destructive, such as flow cytometry, or cannot image throughout a spheroid, such as confocal microscopy. Our group previously developed a wide-field fluorescence hyperspectral imaging system to study spheroids formed and cultured in microfluidic chips. In the present study, two subclones of a single parental ovarian cancer cell line transfected to express different fluorophores were produced and co-culture spheroids were formed on-chip using ratios forming highly asymmetric subpopulations. We performed a 3D proliferation assay on each cell population forming the spheroids that matched the 2D growth behaviour. Response assays to PARP inhibitors and platinum-based drugs were also performed to follow the clonal evolution of mixed populations. Our experiments show that hyperspectral imaging can detect spheroid response before observing a decrease in spheroid diameter. Hyperspectral imaging and microfluidic-based spheroid assays provide a versatile solution to study clonal heterogeneity, able to measure response in subpopulations presenting as little as 10% of the initial spheroid.}, } @article {pmid31171786, year = {2019}, author = {Rossy, T and Nadell, CD and Persat, A}, title = {Cellular advective-diffusion drives the emergence of bacterial surface colonization patterns and heterogeneity.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {2471}, pmid = {31171786}, issn = {2041-1723}, support = {P20 GM113132/GM/NIGMS NIH HHS/United States ; MCB 1817342//National Science Foundation (NSF)/International ; P20-GM113132//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/International ; 31003A_169377//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/International ; STANTO15RO//Cystic Fibrosis Foundation (CF Foundation)/International ; }, mesh = {*Bacterial Adhesion ; *Biofilms ; Caulobacter crescentus/*physiology ; *Hydrodynamics ; }, abstract = {Microorganisms navigate and divide on surfaces to form multicellular structures called biofilms, the most widespread survival strategy found in the bacterial world. One common assumption is that cellular components guide the spatial architecture and arrangement of multiple species in a biofilm. However, bacteria must contend with mechanical forces generated through contact with surfaces and under fluid flow, whose contributions to colonization patterns are poorly understood. Here, we show how the balance between motility and flow promotes the emergence of morphological patterns in Caulobacter crescentus biofilms. By modeling transport of single cells by flow and Brownian-like swimming, we show that the emergence of these patterns is guided by an effective Péclet number. By analogy with transport phenomena we show that, counter-intuitively, fluid flow represses mixing of distinct clonal lineages, thereby affecting the interaction landscapes between biofilm-dwelling bacteria. This demonstrates that hydrodynamics influence species interaction and evolution within surface-associated communities.}, } @article {pmid31170405, year = {2019}, author = {Edgar, JA}, title = {L-ascorbic acid and the evolution of multicellular eukaryotes.}, journal = {Journal of theoretical biology}, volume = {476}, number = {}, pages = {62-73}, doi = {10.1016/j.jtbi.2019.06.001}, pmid = {31170405}, issn = {1095-8541}, mesh = {Aerobiosis/physiology ; Ascorbic Acid/*metabolism ; Eukaryotic Cells/cytology/*metabolism ; *Evolution, Molecular ; Photosynthesis/*physiology ; Plants/*metabolism ; }, abstract = {The lifeless earth was formed around 4.5 billion years ago and the first anaerobic unicellular "organisms" may have appeared half a billion years later. Despite subsequent prokaryotes (bacteria and archaea) evolving quite complex biochemistry and some eukaryote characteristics, the transition from unicellular prokaryotes to multicellular, aerobic eukaryotes took a further 2.5 billion years to begin. The key factor or factors that eventually caused this long-delayed transition is a question that has been a focus of considerable research and a topic of discussion over many years. On the basis of the extensive literature available and consideration of some of the characteristics that distinguish multicellular eukaryotes from prokaryotes, it is proposed that, as well as the development of oxygenic photosynthesis producing high levels of environmental oxygen and the formation of vital organelles such as aerobic adenosine triphosphate-generating mitochondria, the concurrent evolution of the L-ascorbic acid redox system should be considered as a key factor that led to the evolution of multicellular eukaryotes and it remains vitally involved in the maintenance of multicellularity and many other eukaryote characteristics.}, } @article {pmid31170137, year = {2019}, author = {Thomas, F and Madsen, T and Giraudeau, M and Misse, D and Hamede, R and Vincze, O and Renaud, F and Roche, B and Ujvari, B}, title = {Transmissible cancer and the evolution of sex.}, journal = {PLoS biology}, volume = {17}, number = {6}, pages = {e3000275}, pmid = {31170137}, issn = {1545-7885}, mesh = {Animals ; Biological Evolution ; Cell Transformation, Neoplastic/genetics ; Eukaryota ; Genotype ; Humans ; Recombination, Genetic/genetics/*physiology ; Reproduction/*genetics/*physiology ; Selection, Genetic/genetics ; Sexual Behavior/physiology ; }, abstract = {The origin and subsequent maintenance of sex and recombination are among the most elusive and controversial problems in evolutionary biology. Here, we propose a novel hypothesis, suggesting that sexual reproduction not only evolved to reduce the negative effects of the accumulation of deleterious mutations and processes associated with pathogen and/or parasite resistance but also to prevent invasion by transmissible selfish neoplastic cheater cells, henceforth referred to as transmissible cancer cells. Sexual reproduction permits systematic change of the multicellular organism's genotype and hence an enhanced detection of transmissible cancer cells by immune system. Given the omnipresence of oncogenic processes in multicellular organisms, together with the fact that transmissible cancer cells can have dramatic effects on their host fitness, our scenario suggests that the benefits of sex and concomitant recombination will be large and permanent, explaining why sexual reproduction is, despite its costs, the dominant mode of reproduction among eukaryotes.}, } @article {pmid31169232, year = {2019}, author = {Siddiqui, S and Singh, A and Faizi, N and Khalid, A}, title = {Cell cannibalism in oral cancer: A sign of aggressiveness, de-evolution, and retroversion of multicellularity.}, journal = {Journal of cancer research and therapeutics}, volume = {15}, number = {3}, pages = {631-637}, doi = {10.4103/jcrt.JCRT_504_17}, pmid = {31169232}, issn = {1998-4138}, mesh = {Aged ; Aged, 80 and over ; Analysis of Variance ; Biomarkers, Tumor ; *Cytophagocytosis ; Disease Progression ; Energy Metabolism ; Female ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/immunology/metabolism/pathology ; Male ; Middle Aged ; Mouth Neoplasms/etiology/metabolism/*pathology ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Neutrophil Infiltration/immunology ; }, abstract = {BACKGROUND: According to Darwin's theory of evolution, complex creatures evolve from more simplistic ancestors. Dollo's law of irreversibility states that evolution is irreversible. However, cancer cells tend to follow anti-Dollo's law. Unfavorable conditions such as hypoxia, acidic pH and low nutrients cause the cancer cells to switch their lifestyle atavistically in order to survive. They start behaving like a unicellular organism. There is a switch from normal metabolism to Warburg effect and finally cannibalism. Cannibalism is a cell eating cell phenomenon. It is defined as a large cell enclosing a smaller one within its cytoplasm and is known by odd names such as "bird's eye cells" or "signet ring cells." Smaller tumor cells are found in the cytoplasm of larger tumor cells with crescent-shaped nucleus. Cannibalistic cells (CCs) are a feature of aggressive tumors. These cell types are vulnerable to metastasis.

AIM: The aim of this study is to identify CCs in various histological grades of oral squamous cell carcinoma (OSCC) and to relate them with the pattern of invasion, lymphocytic response (LR), and mitotic figures (Mfs). The purpose of the article is to establish it as a marker of aggressiveness and metastasis and as an evidence of de-evolution and retroversion of multicellularity.

MATERIALS AND METHODS: Sixty-five histologically confirmed cases of OSCC were studied. Pattern of invasion, LR, number of CCs, and Mfs were recorded on 5 μ hematoxylin and eosin-stained tissue sections. ANOVA and t-test were applied; P < 0.05 was considered statistically significant.

RESULTS: CCs were more in sections with patchy LR, increased Mfs, and grade IV pattern of invasion.

CONCLUSION: With increase in dedifferentiation, tumor cells start behaving like unicellular organisms with cell eating cell characteristics.}, } @article {pmid31163162, year = {2019}, author = {Ostrowski, EA}, title = {Enforcing Cooperation in the Social Amoebae.}, journal = {Current biology : CB}, volume = {29}, number = {11}, pages = {R474-R484}, doi = {10.1016/j.cub.2019.04.022}, pmid = {31163162}, issn = {1879-0445}, mesh = {*Biological Evolution ; Dictyostelium/*physiology ; *Microbial Interactions ; }, abstract = {Cooperation has been essential to the evolution of biological complexity, but many societies struggle to overcome internal conflicts and divisions. Dictyostelium discoideum, or the social amoeba, has been a useful model system for exploring these conflicts and how they can be resolved. When starved, these cells communicate, gather into groups, and build themselves into a multicellular fruiting body. Some cells altruistically die to form the rigid stalk, while the remainder sit atop the stalk, become spores, and disperse. Evolutionary theory predicts that conflict will arise over which cells die to form the stalk and which cells become spores and survive. The power of the social amoeba lies in the ability to explore how cooperation and conflict work across multiple levels, ranging from proximate mechanisms (how does it work?) to ultimate evolutionary answers (why does it work?). Recent studies point to solutions to the problem of ensuring fairness, such as the ability to suppress selfishness and to recognize and avoid unrelated individuals. This work confirms a central role for kin selection, but also suggests new explanations for how social amoebae might enforce cooperation. New approaches based on genomics are also enabling researchers to decipher for the first time the evolutionary history of cooperation and conflict and to determine its role in shaping the biology of multicellular organisms.}, } @article {pmid31163154, year = {2019}, author = {Smith, P and Schuster, M}, title = {Public goods and cheating in microbes.}, journal = {Current biology : CB}, volume = {29}, number = {11}, pages = {R442-R447}, doi = {10.1016/j.cub.2019.03.001}, pmid = {31163154}, issn = {1879-0445}, mesh = {*Biological Evolution ; *Microbial Interactions ; Models, Biological ; }, abstract = {Communication and cooperation are not restricted to complex, higher organisms. Microbes, too, perform a variety of collective, multicellular behaviors, including biofilm formation, quorum sensing, nutrient acquisition, and dispersal. The products of these microbial cooperative behaviors are generally referred to as public goods. Here we describe the nature of microbial public goods, the associated problem of cheating, and ways in which microbes maintain public goods in the face of cheating. We highlight work in a growing field at the interface of microbiology, evolution, and ecology that combines multiple approaches in experimental evolution, genetics, and mathematical modeling.}, } @article {pmid31158828, year = {2019}, author = {Sample, M and Boulicault, M and Allen, C and Bashir, R and Hyun, I and Levis, M and Lowenthal, C and Mertz, D and Montserrat, N and Palmer, MJ and Saha, K and Zartman, J}, title = {Multi-cellular engineered living systems: building a community around responsible research on emergence.}, journal = {Biofabrication}, volume = {11}, number = {4}, pages = {043001}, pmid = {31158828}, issn = {1758-5090}, support = {R35 GM119644/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biomedical Research ; Cell Engineering/ethics/*methods ; }, abstract = {Ranging from miniaturized biological robots to organoids, multi-cellular engineered living systems (M-CELS) pose complex ethical and societal challenges. Some of these challenges, such as how to best distribute risks and benefits, are likely to arise in the development of any new technology. Other challenges arise specifically because of the particular characteristics of M-CELS. For example, as an engineered living system becomes increasingly complex, it may provoke societal debate about its moral considerability, perhaps necessitating protection from harm or recognition of positive moral and legal rights, particularly if derived from cells of human origin. The use of emergence-based principles in M-CELS development may also create unique challenges, making the technology difficult to fully control or predict in the laboratory as well as in applied medical or environmental settings. In response to these challenges, we argue that the M-CELS community has an obligation to systematically address the ethical and societal aspects of research and to seek input from and accountability to a broad range of stakeholders and publics. As a newly developing field, M-CELS has a significant opportunity to integrate ethically responsible norms and standards into its research and development practices from the start. With the aim of seizing this opportunity, we identify two general kinds of salient ethical issues arising from M-CELS research, and then present a set of commitments to and strategies for addressing these issues. If adopted, these commitments and strategies would help define M-CELS as not only an innovative field, but also as a model for responsible research and engineering.}, } @article {pmid31155362, year = {2019}, author = {Russell, SL and Chappell, L and Sullivan, W}, title = {A symbiont's guide to the germline.}, journal = {Current topics in developmental biology}, volume = {135}, number = {}, pages = {315-351}, doi = {10.1016/bs.ctdb.2019.04.007}, pmid = {31155362}, issn = {1557-8933}, mesh = {Animals ; Cell Movement ; Embryo, Nonmammalian/microbiology ; Germ Cells/*physiology ; Stem Cells/cytology ; *Symbiosis ; }, abstract = {Microbial symbioses exhibit astounding adaptations, yet all symbionts face the problem of how to reliably associate with host offspring every generation. A common strategy is vertical transmission, in which symbionts are directly transmitted from the female to her offspring. The diversity of symbionts and vertical transmission mechanisms is as expansive as the diversity of eukaryotic host taxa that house them. However, there are several common themes among these mechanisms based on the degree to which symbionts associate with the host germline during transmission. In this review, we detail three distinct vertical transmission strategies, starting with associations that are transmitted from host somatic cells to offspring somatic cells, either due to lacking a germline or avoiding it. A second strategy involves somatically-localized symbionts that migrate into the germline during host development. The third strategy we discuss is one in which the symbiont maintains continuous association with the germline throughout development. Unexpectedly, the vast majority of documented vertically inherited symbionts rely on the second strategy: soma-to-germline migration. Given that not all eukaryotes contain a sequestered germline and instead produce offspring from somatic stem cell lineages, this soma-to-germline migration is discussed in the context of multicellular evolution. Lastly, as recent genomics data have revealed an abundance of horizontal gene transfer events from symbiotic and non-symbiotic bacteria to host genomes, we discuss their impact on eukaryotic host evolution.}, } @article {pmid31152521, year = {2019}, author = {Odendall, C and Kagan, JC}, title = {Host-Encoded Sensors of Bacteria: Our Windows into the Microbial World.}, journal = {Microbiology spectrum}, volume = {7}, number = {3}, pages = {}, pmid = {31152521}, issn = {2165-0497}, support = {R01 AI093589/AI/NIAID NIH HHS/United States ; R37 AI116550/AI/NIAID NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; U19 AI133524/AI/NIAID NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R01 AI116550/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*immunology/pathogenicity ; Bacterial Infections/*immunology/microbiology ; Evolution, Molecular ; Germ-Free Life ; Host-Pathogen Interactions/*immunology/*physiology ; Humans ; Neutrophil Infiltration ; Receptors, Pattern Recognition/immunology/*physiology ; Virulence Factors ; }, abstract = {Bacterial pathogens can be very efficient at causing disease and are the cause of some of the worst epidemics that have affected humanity. However, most infections are prevented by the actions of our immune system. Immune activation depends on the rapid detection of bacteria by a diverse family of sensory proteins known as pattern recognition receptors. These receptors detect conserved features of bacteria that are not found in humans but are often necessary for survival within the host or environment. In this review, we discuss the strategies used by pattern recognition receptors to detect bacteria and their products. We also discuss emerging evidence that some pattern recognition receptors can be activated by bacterial pathogens specifically, through the surveillance of host activities that are commonly targeted by virulence factors. This collection of surveillance mechanisms provides an interconnected network of defense, which is important to maintain the germ-free environment of the inner organs of humans and other multicellular organisms.}, } @article {pmid31150287, year = {2019}, author = {Moreno, MA and Ofria, C}, title = {Toward Open-Ended Fraternal Transitions in Individuality.}, journal = {Artificial life}, volume = {25}, number = {2}, pages = {117-133}, doi = {10.1162/artl_a_00284}, pmid = {31150287}, issn = {1530-9185}, mesh = {*Biological Evolution ; *Individuality ; Models, Biological ; *Reproduction ; }, abstract = {The emergence of new replicating entities from the union of simpler entities characterizes some of the most profound events in natural evolutionary history. Such transitions in individuality are essential to the evolution of the most complex forms of life. Thus, understanding these transitions is critical to building artificial systems capable of open-ended evolution. Alas, these transitions are challenging to induce or detect, even with computational organisms. Here, we introduce the DISHTINY (Distributed Hierarchical Transitions in Individuality) platform, which provides simple cell-like organisms with the ability and incentive to unite into new individuals in a manner that can continue to scale to subsequent transitions. The system is designed to encourage these transitions so that they can be studied: Organisms that coordinate spatiotemporally can maximize the rate of resource harvest, which is closely linked to their reproductive ability. We demonstrate the hierarchical emergence of multiple levels of individuality among simple cell-like organisms that evolve parameters for manually designed strategies. During evolution, we observe reproductive division of labor and close cooperation among cells, including resource-sharing, aggregation of resource endowments for propagules, and emergence of an apoptosis response to somatic mutation. Many replicate populations evolved to direct their resources toward low-level groups (behaving like multicellular individuals), and many others evolved to direct their resources toward high-level groups (acting as larger-scale multicellular individuals).}, } @article {pmid31142622, year = {2019}, author = {Sweeney, EG and Nishida, A and Weston, A and Bañuelos, MS and Potter, K and Conery, J and Guillemin, K}, title = {Agent-Based Modeling Demonstrates How Local Chemotactic Behavior Can Shape Biofilm Architecture.}, journal = {mSphere}, volume = {4}, number = {3}, pages = {}, pmid = {31142622}, issn = {2379-5042}, support = {P01 GM125576/GM/NIGMS NIH HHS/United States ; R01 DK101314/DK/NIDDK NIH HHS/United States ; T32 GM007759/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Physiological Phenomena ; Biofilms/*growth & development ; *Chemotaxis ; *Computer Simulation ; Helicobacter pylori/*physiology ; Homoserine/analogs & derivatives/metabolism ; Lactones/metabolism ; Quorum Sensing ; }, abstract = {Bacteria are often found living in aggregated multicellular communities known as biofilms. Biofilms are three-dimensional structures that confer distinct physical and biological properties to the collective of cells living within them. We used agent-based modeling to explore whether local cellular interactions were sufficient to give rise to global structural features of biofilms. Specifically, we asked whether chemorepulsion from a self-produced quorum-sensing molecule, autoinducer-2 (AI-2), was sufficient to recapitulate biofilm growth and cellular organization observed for biofilms of Helicobacter pylori, a common bacterial resident of human stomachs. To carry out this modeling, we modified an existing platform, Individual-based Dynamics of Microbial Communities Simulator (iDynoMiCS), to incorporate three-dimensional chemotaxis, planktonic cells that could join or leave the biofilm structure, and cellular production of AI-2. We simulated biofilm growth of previously characterized H. pylori strains with various AI-2 production and sensing capacities. Using biologically plausible parameters, we were able to recapitulate both the variation in biofilm mass and cellular distributions observed with these strains. Specifically, the strains that were competent to chemotax away from AI-2 produced smaller and more heterogeneously spaced biofilms, whereas the AI-2 chemotaxis-defective strains produced larger and more homogeneously spaced biofilms. The model also provided new insights into the cellular demographics contributing to the biofilm patterning of each strain. Our analysis supports the idea that cellular interactions at small spatial and temporal scales are sufficient to give rise to larger-scale emergent properties of biofilms.IMPORTANCE Most bacteria exist in aggregated, three-dimensional structures called biofilms. Although biofilms play important ecological roles in natural and engineered settings, they can also pose societal problems, for example, when they grow in plumbing systems or on medical implants. Understanding the processes that promote the growth and disassembly of biofilms could lead to better strategies to manage these structures. We had previously shown that Helicobacter pylori bacteria are repulsed by high concentrations of a self-produced molecule, AI-2, and that H. pylori mutants deficient in AI-2 sensing form larger and more homogeneously spaced biofilms. Here, we used computer simulations of biofilm formation to show that local H. pylori behavior of repulsion from high AI-2 could explain the overall architecture of H. pylori biofilms. Our findings demonstrate that it is possible to change global biofilm organization by manipulating local cell behaviors, which suggests that simple strategies targeting cells at local scales could be useful for controlling biofilms in industrial and medical settings.}, } @article {pmid31118944, year = {2019}, author = {Liu, T and Wang, X and Wang, G and Jia, S and Liu, G and Shan, G and Chi, S and Zhang, J and Yu, Y and Xue, T and Yu, J}, title = {Evolution of Complex Thallus Alga: Genome Sequencing of Saccharina japonica.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {378}, pmid = {31118944}, issn = {1664-8021}, abstract = {Saccharina, as one of the most important brown algae (Phaeophyceae) with multicellular thallus, has a very remarkable evolutionary history, and globally accounts for most of the economic marine aquaculture production worldwide. Here, we present the 580.5 million base pairs of genome sequence of Saccharina japonica, whose current assembly contains 35,725 protein-coding genes. In a comparative analysis with Ectocarpus siliculosus, the integrated virus sequence suggested the genome evolutionary footprints, which derived from their co-ancestry and experienced genomic arrangements. Furthermore, the gene expansion was found to be an important strategy for functional evolution, especially with regard to extracelluar components, stress-related genes, and vanadium-dependent haloperoxidases, and we proposed a hypothesis that gene duplication events were the main driving force for the evolution history from multicellular filamentous algae to thallus algae. The sequenced Saccharina genome paves the way for further molecular studies and is useful for genome-assisted breeding of S. japonica and other related algae species.}, } @article {pmid31118507, year = {2019}, author = {Loron, CC and François, C and Rainbird, RH and Turner, EC and Borensztajn, S and Javaux, EJ}, title = {Early fungi from the Proterozoic era in Arctic Canada.}, journal = {Nature}, volume = {570}, number = {7760}, pages = {232-235}, doi = {10.1038/s41586-019-1217-0}, pmid = {31118507}, issn = {1476-4687}, mesh = {Arctic Regions ; Canada ; *Fossils ; Fungi/*classification/*isolation & purification/ultrastructure ; History, Ancient ; Phylogeny ; Spectroscopy, Fourier Transform Infrared ; Time Factors ; }, abstract = {Fungi are crucial components of modern ecosystems. They may have had an important role in the colonization of land by eukaryotes, and in the appearance and success of land plants and metazoans[1-3]. Nevertheless, fossils that can unambiguously be identified as fungi are absent from the fossil record until the middle of the Palaeozoic era[4,5]. Here we show, using morphological, ultrastructural and spectroscopic analyses, that multicellular organic-walled microfossils preserved in shale of the Grassy Bay Formation (Shaler Supergroup, Arctic Canada), which dates to approximately 1,010-890 million years ago, have a fungal affinity. These microfossils are more than half a billion years older than previously reported unambiguous occurrences of fungi, a date which is consistent with data from molecular clocks for the emergence of this clade[6,7]. In extending the fossil record of the fungi, this finding also pushes back the minimum date for the appearance of eukaryotic crown group Opisthokonta, which comprises metazoans, fungi and their protist relatives[8,9].}, } @article {pmid31115328, year = {2019}, author = {Bornens, M}, title = {[Cell polarity and the innovation of the primary cilium/centrosome organ in Metazoa].}, journal = {Medecine sciences : M/S}, volume = {35}, number = {5}, pages = {452-461}, doi = {10.1051/medsci/2019092}, pmid = {31115328}, issn = {1958-5381}, mesh = {Animals ; Biological Evolution ; Brain/growth & development ; Cell Movement ; Cell Polarity ; Centrosome/*physiology ; Cilia/*physiology ; Embryonic Development ; Flagella ; Humans ; Sensation ; }, abstract = {Cell-autonomous polarity in Metazoans is inherited from ancestral unicellular organisms. We assume that permanent polarity in unicellular eukaryotes is required for cell motion and sensory reception and that the integration of these two activities corresponds to an evolutionary constrained cell function. While conserving the ancestral flagellum, Metazoans have co-opted a primary cilium/centrosome organ from it, ensuring similar functions, but in different cells, or in the same cell at different moments. We propose that the remodeling necessary to reach a new higher-level unit of selection in multi-cellular organisms, has been triggered by conflicts among individual cell polarities to reach an organismic polarity. We shall provisionally conclude that beyond critical consequences for embryo development, the conservation of cell-autonomous polarity in Metazoans has far reaching implications for the evolution of individuality.}, } @article {pmid31113629, year = {2019}, author = {Ballinger, MJ and Perlman, SJ}, title = {The defensive Spiroplasma.}, journal = {Current opinion in insect science}, volume = {32}, number = {}, pages = {36-41}, doi = {10.1016/j.cois.2018.10.004}, pmid = {31113629}, issn = {2214-5753}, mesh = {Animals ; Arthropods/*microbiology/*parasitology ; Fungi ; Nematoda ; Saporins ; Spiroplasma/*physiology ; Symbiosis ; Wasps ; }, abstract = {Defensive microbes are of great interest for their roles in arthropod health, disease transmission, and biocontrol efforts. Obligate bacterial passengers of arthropods, such as Spiroplasma, confer protection against the natural enemies of their hosts to improve their own fitness. Although known for less than a decade, Spiroplasma's defensive reach extends to diverse parasites, both microbial and multicellular. We provide an overview of known defensive phenotypes against nematodes, parasitoid wasps, and fungi, and highlight recent studies supporting the role of Spiroplasma-encoded ribosome-inactivating proteins in protection. With cellular features well-suited for life in the hemolymph, broad distribution among invertebrate hosts, and the capacity to repeatedly evolve vertical transmission, Spiroplasma may be uniquely equipped to form intimate, defensive associations to combat extracellular parasites. Along with insights into defensive mechanisms, recent significant advances have been made in male-killing - a phenotype with interesting evolutionary ties to defense. Finally, we look forward to an exciting decade using the genetic tools of Drosophila, and the rapidly-advancing tractability of Spiroplasma itself, to better understand mechanisms and evolution in defensive symbiosis.}, } @article {pmid31102790, year = {2019}, author = {Ebrahimkhani, MR and Ebisuya, M}, title = {Synthetic developmental biology: build and control multicellular systems.}, journal = {Current opinion in chemical biology}, volume = {52}, number = {}, pages = {9-15}, doi = {10.1016/j.cbpa.2019.04.006}, pmid = {31102790}, issn = {1879-0402}, mesh = {Cell Communication ; *Developmental Biology ; *Embryonic Development ; Gene Regulatory Networks ; Morphogenesis ; Organoids ; Stem Cells/cytology ; *Synthetic Biology ; }, abstract = {Synthetic biology offers a bottom-up engineering approach that intends to understand complex systems via design-build-test cycles. Embryonic development comprises complex processes that originate at the level of gene regulatory networks in a cell and emerge into collective cellular behaviors with multicellular forms and functions. Here, we review synthetic biology approaches to development that involve building de novo developmental trajectories or engineering control in stem cell-derived multicellular systems. The field of synthetic developmental biology is rapidly growing with the help of recent advances in artificial gene circuits, self-organizing organoids, and controllable tissue microenvironments. The outcome will be a blueprint to decode principles of morphogenesis and to create programmable organoids with novel designs or improved functions.}, } @article {pmid31095603, year = {2019}, author = {Khan, MAW and Stephens, WZ and Mohammed, AD and Round, JL and Kubinak, JL}, title = {Does MHC heterozygosity influence microbiota form and function?.}, journal = {PloS one}, volume = {14}, number = {5}, pages = {e0215946}, pmid = {31095603}, issn = {1932-6203}, support = {DP2 AT008746/AT/NCCIH NIH HHS/United States ; N01AI95375/AI/NIAID NIH HHS/United States ; T32 AI055434/AI/NIAID NIH HHS/United States ; K22 AI123481/AI/NIAID NIH HHS/United States ; R56 AI107090/AI/NIAID NIH HHS/United States ; K22 AI095375/AI/NIAID NIH HHS/United States ; R21 AI109122/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Feces/microbiology ; Female ; Genetic Variation ; Genotype ; *Heterozygote ; Homozygote ; Major Histocompatibility Complex/*genetics ; Mice ; Microbiota/*genetics ; }, abstract = {MHC molecules are essential for the adaptive immune response, and they are the most polymorphic genetic loci in vertebrates. Extreme genetic variation at these loci is paradoxical given their central importance to host health. Classic models of MHC gene evolution center on antagonistic host-pathogen interactions to promote gene diversification and allelic diversity in host populations. However, all multicellular organisms are persistently colonized by their microbiota that perform essential metabolic functions for their host and protect from infection. Here, we provide data to support the hypothesis that MHC heterozygote advantage (a main force of selection thought to drive MHC gene evolution), may operate by enhancing fitness advantages conferred by the host's microbiome. We utilized fecal 16S rRNA gene sequences and their predicted metagenome datasets collected from multiple MHC congenic homozygote and heterozygote mouse strains to describe the influence of MHC heterozygosity on microbiome form and function. We find that in contrast to homozygosity at MHC loci, MHC heterozygosity promotes functional diversification of the microbiome, enhances microbial network connectivity, and results in enrichment for a variety of microbial functions that are positively associated with host fitness. We demonstrate that taxonomic and functional diversity of the microbiome is positively correlated in MHC heterozygote but not homozygote animals, suggesting that heterozygote microbiomes are more functionally adaptive under similar environmental conditions than homozygote microbiomes. Our data complement previous observations on the role of MHC polymorphism in sculpting microbiota composition, but also provide functional insights into how MHC heterozygosity may enhance host health by modulating microbiome form and function. We also provide evidence to support that MHC heterozygosity limits functional redundancy among commensal microbes and may enhance the metabolic versatility of their microbiome. Results from our analyses yield multiple testable predictions regarding the role of MHC heterozygosity on the microbiome that will help guide future research in the area of MHC-microbiome interactions.}, } @article {pmid31088261, year = {2019}, author = {Pichugin, Y and Park, HJ and Traulsen, A}, title = {Evolution of simple multicellular life cycles in dynamic environments.}, journal = {Journal of the Royal Society, Interface}, volume = {16}, number = {154}, pages = {20190054}, pmid = {31088261}, issn = {1742-5662}, mesh = {Animals ; *Biological Evolution ; *Environment ; *Life Cycle Stages ; *Models, Biological ; Reproduction ; *Selection, Genetic ; }, abstract = {The mode of reproduction is a critical characteristic of any species, as it has a strong effect on its evolution. As any other trait, the reproduction mode is subject to natural selection and may adapt to the environment. When the environment varies over time, different reproduction modes could be optimal at different times. The natural response to a dynamic environment seems to be bet hedging, where multiple reproductive strategies are stochastically executed. Here, we develop a framework for the evolution of simple multicellular life cycles in a dynamic environment. We use a matrix population model of undifferentiated multicellular groups undergoing fragmentation and ask which mode maximizes the population growth rate. Counterintuitively, we find that natural selection in dynamic environments generally tends to promote deterministic, not stochastic, reproduction modes.}, } @article {pmid31086369, year = {2019}, author = {Gao, Y and Traulsen, A and Pichugin, Y}, title = {Interacting cells driving the evolution of multicellular life cycles.}, journal = {PLoS computational biology}, volume = {15}, number = {5}, pages = {e1006987}, pmid = {31086369}, issn = {1553-7358}, mesh = {Animals ; Biological Evolution ; Cell Communication/*physiology ; Cell Division ; Computer Simulation ; Game Theory ; Humans ; Life Cycle Stages/genetics/*physiology ; Models, Biological ; Phenotype ; Reproduction ; }, abstract = {Evolution of complex multicellular life began from the emergence of a life cycle involving the formation of cell clusters. The opportunity for cells to interact within clusters provided them with an advantage over unicellular life forms. However, what kind of interactions may lead to the evolution of multicellular life cycles? Here, we combine evolutionary game theory with a model for the emergence of multicellular groups to investigate how cell interactions can influence reproduction modes during the early stages of the evolution of multicellularity. In our model, the presence of both cell types is maintained by stochastic phenotype switching during cell division. We identify evolutionary optimal life cycles as those which maximize the population growth rate. Among all interactions captured by two-player games, the vast majority promotes two classes of life cycles: (i) splitting into unicellular propagules or (ii) fragmentation into two offspring clusters of equal (or almost equal) size. Our findings indicate that the three most important characteristics, determining whether multicellular life cycles will evolve, are the average performance of homogeneous groups, heterogeneous groups, and solitary cells.}, } @article {pmid31086336, year = {2019}, author = {Chan, MM and Smith, ZD and Grosswendt, S and Kretzmer, H and Norman, TM and Adamson, B and Jost, M and Quinn, JJ and Yang, D and Jones, MG and Khodaverdian, A and Yosef, N and Meissner, A and Weissman, JS}, title = {Molecular recording of mammalian embryogenesis.}, journal = {Nature}, volume = {570}, number = {7759}, pages = {77-82}, pmid = {31086336}, issn = {1476-4687}, support = {T32 HG000047/HG/NHGRI NIH HHS/United States ; F32 GM116331/GM/NIGMS NIH HHS/United States ; RM1 HG009490/HG/NHGRI NIH HHS/United States ; R01 DA036858/DA/NIDA NIH HHS/United States ; R01 HD078679/HD/NICHD NIH HHS/United States ; P50 HG006193/HG/NHGRI NIH HHS/United States ; F32 GM125247/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/genetics ; Cell Lineage/genetics ; Embryo, Mammalian/cytology/*embryology/*metabolism ; Embryonic Development/*genetics ; Embryonic Stem Cells/cytology/metabolism ; Endoderm/embryology/metabolism ; Female ; Fertilization ; Gastrulation ; Gene Expression Regulation, Developmental/genetics ; Male ; Mice ; Organ Specificity/genetics ; Phenotype ; Sequence Analysis, RNA ; Single-Cell Analysis ; }, abstract = {Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. This field is particularly challenging in mammals, owing to the indeterminate relationship between self-renewal and differentiation, variation in progenitor field sizes, and internal gestation in these animals. Here we present a flexible, high-information, multi-channel molecular recorder with a single-cell readout and apply it as an evolving lineage tracer to assemble mouse cell-fate maps from fertilization through gastrulation. By combining lineage information with single-cell RNA sequencing profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells of extra-embryonic and embryonic origins. Finally, we apply our cell-fate maps to estimate the number of embryonic progenitor cells and their degree of asymmetric partitioning during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems, which will facilitate the construction of a quantitative framework for understanding developmental processes.}, } @article {pmid31077747, year = {2019}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Evolutionary framework of the human interactome: Unicellular and multicellular giant clusters.}, journal = {Bio Systems}, volume = {181}, number = {}, pages = {82-87}, doi = {10.1016/j.biosystems.2019.05.004}, pmid = {31077747}, issn = {1872-8324}, mesh = {*Biological Evolution ; Cluster Analysis ; *Databases, Genetic ; Evolution, Molecular ; Humans ; Protein Interaction Domains and Motifs ; Protein Interaction Mapping/*methods ; Protein Interaction Maps/*genetics ; }, abstract = {The main contradiction of multicellularity (MCM) is between the unicellular (UC) and multicellular (MC) levels. In human interactome we revealed two giant clusters with MC and UC medians (and several smaller ones with MC medians). The enrichment of these clusters by phylostrata and by functions support the MC versus UC division. The total interactome and the giant clusters show a core-periphery evolutionary growth. From viewpoint of the MCM, the most important is the placement of genes, appearing at UC evolutionary stage, in the MC clusters. Thus, genes involved in vesicle-mediated transport, cell cycle, cellular responses to stress, post-translational modifications and many diseases appeared at UC evolutionary stage but are placed mostly in MC clusters. Genes downregulated with age are enriched in UC cluster, whereas the upregulated genes are preferentially placed in MC giant cluster. The tumor suppressor and pluripotency regulating pathways are also enriched in MC giant cluster. Therefore, this cluster probably operates as 'internal manager' constraining runaway unicellularity. The clusters have denser interactions within than between them, therefore they can serve as attractors (stable states of dynamic systems) of cellular programs. Importantly, the UC cluster have a higher inside/outside connection ratio compared with MC clusters, which suggests a stronger attractor effect and may explain why cells of MC organisms are prone to oncogenesis. The evolutionary clustering of human interactome elucidates the MC control over functions appearing at UC evolutionary stage and can build a framework for biosystems studies focusing on the interplay between UC and MC levels.}, } @article {pmid31069269, year = {2019}, author = {Erkenbrack, EM and Thompson, JR}, title = {Cell type phylogenetics informs the evolutionary origin of echinoderm larval skeletogenic cell identity.}, journal = {Communications biology}, volume = {2}, number = {}, pages = {160}, pmid = {31069269}, issn = {2399-3642}, mesh = {Animal Shells/anatomy & histology/cytology/growth & development/*metabolism ; Animals ; Bayes Theorem ; Biological Evolution ; Echinodermata/classification/*genetics ; Embryo, Nonmammalian ; Extinction, Biological ; Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Larva/cytology/growth & development/*metabolism ; Mesoderm/cytology/growth & development/metabolism ; *Phylogeny ; Stem Cells/cytology/metabolism ; }, abstract = {The multiplicity of cell types comprising multicellular organisms begs the question as to how cell type identities evolve over time. Cell type phylogenetics informs this question by comparing gene expression of homologous cell types in distantly related taxa. We employ this approach to inform the identity of larval skeletogenic cells of echinoderms, a clade for which there are phylogenetically diverse datasets of spatial gene expression patterns. We determined ancestral spatial expression patterns of alx1, ets1, tbr, erg, and vegfr, key components of the skeletogenic gene regulatory network driving identity of the larval skeletogenic cell. Here we show ancestral state reconstructions of spatial gene expression of extant eleutherozoan echinoderms support homology and common ancestry of echinoderm larval skeletogenic cells. We propose larval skeletogenic cells arose in the stem lineage of eleutherozoans during a cell type duplication event that heterochronically activated adult skeletogenic cells in a topographically distinct tissue in early development.}, } @article {pmid31069245, year = {2018}, author = {Wang, P and Liang, J and Shi, LZ and Wang, Y and Zhang, P and Ouyang, M and Preece, D and Peng, Q and Shao, L and Fan, J and Sun, J and Li, SS and Berns, MW and Zhao, H and Wang, Y}, title = {Visualizing Spatiotemporal Dynamics of Intercellular Mechanotransmission upon Wounding.}, journal = {ACS photonics}, volume = {5}, number = {9}, pages = {3565-3574}, pmid = {31069245}, issn = {2330-4022}, support = {R01 GM126016/GM/NIGMS NIH HHS/United States ; R01 GM125379/GM/NIGMS NIH HHS/United States ; R33 CA204704/CA/NCI NIH HHS/United States ; R01 HL121365/HL/NHLBI NIH HHS/United States ; R21 CA209629/CA/NCI NIH HHS/United States ; }, abstract = {During cell-to-cell communications, the interplay between physical and biochemical cues is essential for informational exchange and functional coordination, especially in multicellular organisms. However, it remains a challenge to visualize intercellular signaling dynamics in single live cells. Here, we report a photonic approach, based on laser microscissors and Förster resonance energy transfer (FRET) microscopy, to study intercellular signaling transmission. First, using our high-throughput screening platform, we developed a highly sensitive FRET-based biosensor (SCAGE) for Src kinase, a key regulator of intercellular interactions and signaling cascades. Notably, SCAGE showed a more than 40-fold sensitivity enhancement than the original biosensor in live mammalian cells. Next, upon local severance of physical intercellular connections by femtosecond laser pulses, SCAGE enabled the visualization of a transient Src activation across neighboring cells. Lastly, we found that this observed transient Src activation following the loss of cell-cell contacts depends on the passive structural support of cytoskeleton but not on the active actomyosin contractility. Hence, by precisely introducing local physical perturbations and directly visualizing spatiotemporal transmission of ensuing signaling events, our integrated approach could be broadly applied to mimic and investigate the wounding process at single-cell resolutions. This integrated approach with highly sensitive FRET-based biosensors provides a unique system to advance our in-depth understanding of molecular mechanisms underlying the physical-biochemical basis of intercellular coupling and wounding processes.}, } @article {pmid31062469, year = {2019}, author = {Turan, ZG and Parvizi, P and Dönertaş, HM and Tung, J and Khaitovich, P and Somel, M}, title = {Molecular footprint of Medawar's mutation accumulation process in mammalian aging.}, journal = {Aging cell}, volume = {18}, number = {4}, pages = {e12965}, pmid = {31062469}, issn = {1474-9726}, support = {//Science Academy/International ; 114C040//Scientific and Technological Research Council of Turkey/International ; 215Z495//Scientific and Technological Research Council of Turkey/International ; //Middle East Technical University (METU)/International ; }, mesh = {Aging/*genetics ; Alleles ; Animals ; Databases, Genetic ; *Evolution, Molecular ; Genetic Drift ; Humans ; Macaca/genetics ; Mice ; *Mutation Accumulation ; Phenotype ; Rats ; *Selection, Genetic ; *Transcriptome ; Up-Regulation/genetics ; }, abstract = {Medawar's mutation accumulation hypothesis explains aging by the declining force of natural selection with age: Slightly deleterious germline mutations expressed in old age can drift to fixation and thereby lead to aging-related phenotypes. Although widely cited, empirical evidence for this hypothesis has remained limited. Here, we test one of its predictions that genes relatively highly expressed in old adults should be under weaker purifying selection than genes relatively highly expressed in young adults. Combining 66 transcriptome datasets (including 16 tissues from five mammalian species) with sequence conservation estimates across mammals, here we report that the overall conservation level of expressed genes is lower at old age compared to young adulthood. This age-related decrease in transcriptome conservation (ADICT) is systematically observed in diverse mammalian tissues, including the brain, liver, lung, and artery, but not in others, most notably in the muscle and heart. Where observed, ADICT is driven partly by poorly conserved genes being up-regulated during aging. In general, the more often a gene is found up-regulated with age among tissues and species, the lower its evolutionary conservation. Poorly conserved and up-regulated genes have overlapping functional properties that include responses to age-associated tissue damage, such as apoptosis and inflammation. Meanwhile, these genes do not appear to be under positive selection. Hence, genes contributing to old age phenotypes are found to harbor an excess of slightly deleterious alleles, at least in certain tissues. This supports the notion that genetic drift shapes aging in multicellular organisms, consistent with Medawar's mutation accumulation hypothesis.}, } @article {pmid31055860, year = {2019}, author = {Singer, D and Mitchell, EAD and Payne, RJ and Blandenier, Q and Duckert, C and Fernández, LD and Fournier, B and Hernández, CE and Granath, G and Rydin, H and Bragazza, L and Koronatova, NG and Goia, I and Harris, LI and Kajukało, K and Kosakyan, A and Lamentowicz, M and Kosykh, NP and Vellak, K and Lara, E}, title = {Dispersal limitations and historical factors determine the biogeography of specialized terrestrial protists.}, journal = {Molecular ecology}, volume = {28}, number = {12}, pages = {3089-3100}, doi = {10.1111/mec.15117}, pmid = {31055860}, issn = {1365-294X}, mesh = {Amoeba/*genetics ; Animals ; Butterflies/genetics ; Ecosystem ; Eukaryota/genetics ; Genetic Speciation ; Genetic Variation/*genetics ; North America ; *Phylogeny ; Plants/genetics ; Sphagnopsida/growth & development ; }, abstract = {Recent studies show that soil eukaryotic diversity is immense and dominated by micro-organisms. However, it is unclear to what extent the processes that shape the distribution of diversity in plants and animals also apply to micro-organisms. Major diversification events in multicellular organisms have often been attributed to long-term climatic and geological processes, but the impact of such processes on protist diversity has received much less attention as their distribution has often been believed to be largely cosmopolitan. Here, we quantified phylogeographical patterns in Hyalosphenia papilio, a large testate amoeba restricted to Holarctic Sphagnum-dominated peatlands, to test if the current distribution of its genetic diversity can be explained by historical factors or by the current distribution of suitable habitats. Phylogenetic diversity was higher in Western North America, corresponding to the inferred geographical origin of the H. papilio complex, and was lower in Eurasia despite extensive suitable habitats. These results suggest that patterns of phylogenetic diversity and distribution can be explained by the history of Holarctic Sphagnum peatland range expansions and contractions in response to Quaternary glaciations that promoted cladogenetic range evolution, rather than the contemporary distribution of suitable habitats. Species distributions were positively correlated with climatic niche breadth, suggesting that climatic tolerance is key to dispersal ability in H. papilio. This implies that, at least for large and specialized terrestrial micro-organisms, propagule dispersal is slow enough that historical processes may contribute to their diversification and phylogeographical patterns and may partly explain their very high overall diversity.}, } @article {pmid31053584, year = {2019}, author = {Li, J and Zhang, H and Liu, P and Menguy, N and Roberts, AP and Chen, H and Wang, Y and Pan, Y}, title = {Phylogenetic and Structural Identification of a Novel Magnetotactic Deltaproteobacteria Strain, WYHR-1, from a Freshwater Lake.}, journal = {Applied and environmental microbiology}, volume = {85}, number = {14}, pages = {}, pmid = {31053584}, issn = {1098-5336}, mesh = {China ; Deltaproteobacteria/*classification/genetics/ultrastructure ; Ferrosoferric Oxide ; Geologic Sediments/*microbiology ; Lakes/*microbiology ; Magnetosomes/*ultrastructure ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Microscopy, Fluorescence ; *Phylogeny ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/analysis ; }, abstract = {Magnetotactic bacteria (MTB) are phylogenetically diverse prokaryotes that are able to biomineralize intracellular, magnetic chains of magnetite or greigite nanocrystals called magnetosomes. Simultaneous characterization of MTB phylogeny and biomineralization is crucial but challenging because most MTB are extremely difficult to culture. We identify a large rod, bean-like MTB (tentatively named WYHR-1) from freshwater sediments of Weiyang Lake, Xi'an, China, using a coupled fluorescence and scanning electron microscopy approach at the single-cell scale. Phylogenetic analysis of 16S rRNA gene sequences indicates that WYHR-1 is a novel genus from the Deltaproteobacteria class. Transmission electron microscope observations reveal that WYHR-1 cells contain tens of magnetite magnetosomes that are organized into a single chain bundle along the cell long axis. Mature WYHR-1 magnetosomes are bullet-shaped, straight, and elongated along the [001] direction, with a large flat end terminated by a {100} face at the base and a conical top. This crystal morphology is distinctively different from bullet-shaped magnetosomes produced by other MTB in the Deltaproteobacteria class and the Nitrospirae phylum. This indicates that WYHR-1 may have a different crystal growth process and mechanism from other species, which results from species-specific magnetosome biomineralization in MTB.IMPORTANCE Magnetotactic bacteria (MTB) represent a model system for understanding biomineralization and are also studied intensively in biogeomagnetic and paleomagnetic research. However, many uncultured MTB strains have not been identified phylogenetically or investigated structurally at the single-cell level, which limits comprehensive understanding of MTB diversity and their role in biomineralization. We have identified a novel MTB strain, WYHR-1, from a freshwater lake using a coupled fluorescence and scanning electron microscopy approach at the single-cell scale. Our analyses further indicate that strain WYHR-1 represents a novel genus from the Deltaproteobacteria class. In contrast to bullet-shaped magnetosomes produced by other MTB in the Deltaproteobacteria class and the Nitrospirae phylum, WYHR-1 magnetosomes are bullet-shaped, straight, and highly elongated along the [001] direction, are terminated by a large {100} face at their base, and have a conical top. Our findings imply that, consistent with phylogenetic diversity of MTB, bullet-shaped magnetosomes have diverse crystal habits and growth patterns.}, } @article {pmid31046194, year = {2019}, author = {Biscotti, MA and Barucca, M and Carducci, F and Forconi, M and Canapa, A}, title = {The p53 gene family in vertebrates: Evolutionary considerations.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {6}, pages = {171-178}, doi = {10.1002/jez.b.22856}, pmid = {31046194}, issn = {1552-5015}, mesh = {Animals ; *Evolution, Molecular ; *Genes, p53 ; Phylogeny ; Protein Domains ; Vertebrates/classification/*genetics ; }, abstract = {The origin of the p53 gene family predates multicellular life since TP53 members of this gene family have been found in unicellular eukaryotes. In invertebrates one or two genes attributable to a TP53-like or TP63/73-like gene are present. The radiation into three genes, TP53, TP63, and TP73, has been reported as a vertebrate invention. TP53 is considered the "guardian of the genome" given its role in protecting cells against the DNA damage and cellular stressors. TP63 and TP73 play a role in epithelial development and neurogenesis, respectively. The evolution of the p53 gene family has been the subject of considerable analyses even if several questions remain still open. In this study we addressed the evolutionary history of the p53 gene family in vertebrates performing an extended microsyntenic investigation coupled with a phylogenetic analysis, together with protein domain organization and structure assessment. On the basis of our results we discussed a possible evolutionary scenario according to which a TP53/63/73 ancestor form gave rise to the current TP53 and a TP63/73 form, which in turn independently duplicated into two genes in agnathe and gnathostome lineages.}, } @article {pmid31040327, year = {2019}, author = {Salvi, M and Morbiducci, U and Amadeo, F and Santoro, R and Angelini, F and Chimenti, I and Massai, D and Messina, E and Giacomello, A and Pesce, M and Molinari, F}, title = {Automated Segmentation of Fluorescence Microscopy Images for 3D Cell Detection in human-derived Cardiospheres.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {6644}, pmid = {31040327}, issn = {2045-2322}, mesh = {Cell Culture Techniques ; Humans ; *Image Processing, Computer-Assisted/methods ; *Imaging, Three-Dimensional ; *Microscopy, Fluorescence ; Myoblasts, Cardiac/*cytology/*metabolism ; Reproducibility of Results ; Software ; Spheroids, Cellular ; }, abstract = {The 'cardiosphere' is a 3D cluster of cardiac progenitor cells recapitulating a stem cell niche-like microenvironment with a potential for disease and regeneration modelling of the failing human myocardium. In this multicellular 3D context, it is extremely important to decrypt the spatial distribution of cell markers for dissecting the evolution of cellular phenotypes by direct quantification of fluorescent signals in confocal microscopy. In this study, we present a fully automated method, named CARE ('CARdiosphere Evaluation'), for the segmentation of membranes and cell nuclei in human-derived cardiospheres. The proposed method is tested on twenty 3D-stacks of cardiospheres, for a total of 1160 images. Automatic results are compared with manual annotations and two open-source software designed for fluorescence microscopy. CARE performance was excellent in cardiospheres membrane segmentation and, in cell nuclei detection, the algorithm achieved the same performance as two expert operators. To the best of our knowledge, CARE is the first fully automated algorithm for segmentation inside in vitro 3D cell spheroids, including cardiospheres. The proposed approach will provide, in the future, automated quantitative analysis of markers distribution within the cardiac niche-like environment, enabling predictive associations between cell mechanical stresses and dynamic phenotypic changes.}, } @article {pmid31036299, year = {2019}, author = {Borisenko, I and Podgornaya, OI and Ereskovsky, AV}, title = {From traveler to homebody: Which signaling mechanisms sponge larvae use to become adult sponges?.}, journal = {Advances in protein chemistry and structural biology}, volume = {116}, number = {}, pages = {421-449}, doi = {10.1016/bs.apcsb.2019.02.002}, pmid = {31036299}, issn = {1876-1631}, mesh = {Animals ; Epithelial-Mesenchymal Transition ; Larva/cytology/growth & development ; Metamorphosis, Biological ; Porifera/*cytology/embryology/*growth & development ; *Signal Transduction ; }, abstract = {Cell-to-cell signaling is responsible for regulation of many developmental processes such as proliferation, cell migration, survival, cell fate specification and axis patterning. In this article we discussed the role of signaling in the metamorphosis of sponges with a focus on epithelial-mesenchymal transition (EMT) accompanying this event. Sponges (Porifera) are an ancient lineage of morphologically simple animals occupying a basal position on the tree of life. The study of these animals is necessary for understanding the origin of multicellularity and the evolution of developmental processes. Development of sponges is quite diverse. It finishes with the metamorphosis of a free-swimming larva into a young settled sponge. The outer surface of sponge larvae consists of a ciliated epithelial sheath, which ensures locomotion, while their internal structure varies from genus to genus. The fate of larval ciliated cells is the most intriguing aspect of metamorphosis. In this review we discuss the fate of larval ciliated cells, the processes going on in cells during metamorphosis at the molecular level and the regulation of this process. The review is based on information about several sponge species with a focus on Halisarca dujardini, Sycon ciliatum and Amphimedon queenslandica. In our model sponge, H. dujardini, ciliated cells leave the larval epithelium during metamorphosis and migrate to the internal cell mass as amoeboid cells to be differentiated into choanocytes of the juvenile sponge. Ciliated cells undergo EMT and internalize within minutes. As EMT involves the disappearance of adherens junctions and as cadherin, the main adherens junction protein, was identified in the transcriptome of several sponges, we suppose that EMT is regulated through cadherin-containing adherens junctions between ciliated cells. We failed to identify the master genes of EMT in the H. dujardini transcriptome, possibly because transcription was absent in the sequenced stages. They may be revealed by a search in the genome. The master genes themselves are controlled by various signaling pathways. Sponges have all the six signaling pathways conserved in Metazoa: Wnt, TGF-beta, Hedgehog, Notch, FGF and NO-dependent pathways. Summarizing the new data about intercellular communication in sponges, we can put forward two main questions regarding metamorphosis: (1) Which of the signaling pathways and in what hierarchical order are involved in metamorphosis? (2) How is the organization of a young sponge related to that of the larva or, in other words, is there a heredity of axes between the larva and the adult sponge?}, } @article {pmid31032028, year = {2019}, author = {Rivera-Yoshida, N and Arzola, AV and Arias Del Angel, JA and Franci, A and Travisano, M and Escalante, AE and Benítez, M}, title = {Plastic multicellular development of Myxococcus xanthus: genotype-environment interactions in a physical gradient.}, journal = {Royal Society open science}, volume = {6}, number = {3}, pages = {181730}, pmid = {31032028}, issn = {2054-5703}, abstract = {In order to investigate the contribution of the physical environment to variation in multicellular development of Myxococcus xanthus, phenotypes developed by different genotypes in a gradient of substrate stiffness conditions were quantitatively characterized. Statistical analysis showed that plastic phenotypes result from the genotype, the substrate conditions and the interaction between them. Also, phenotypes were expressed in two distinguishable scales, the individual and the population levels, and the interaction with the environment showed scale and trait specificity. Overall, our results highlight the constructive role of the physical context in the development of microbial multicellularity, with both ecological and evolutionary implications.}, } @article {pmid31031789, year = {2019}, author = {Hajheidari, M and Koncz, C and Bucher, M}, title = {Chromatin Evolution-Key Innovations Underpinning Morphological Complexity.}, journal = {Frontiers in plant science}, volume = {10}, number = {}, pages = {454}, pmid = {31031789}, issn = {1664-462X}, abstract = {The history of life consists of a series of major evolutionary transitions, including emergence and radiation of complex multicellular eukaryotes from unicellular ancestors. The cells of multicellular organisms, with few exceptions, contain the same genome, however, their organs are composed of a variety of cell types that differ in both structure and function. This variation is largely due to the transcriptional activity of different sets of genes in different cell types. This indicates that complex transcriptional regulation played a key role in the evolution of complexity in eukaryotes. In this review, we summarize how gene duplication and subsequent evolutionary innovations, including the structural evolution of nucleosomes and chromatin-related factors, contributed to the complexity of the transcriptional system and provided a basis for morphological diversity.}, } @article {pmid31029570, year = {2020}, author = {Turner, P and Nottale, L and Zhao, J and Pesquet, E}, title = {New insights into the physical processes that underpin cell division and the emergence of different cellular and multicellular structures.}, journal = {Progress in biophysics and molecular biology}, volume = {150}, number = {}, pages = {13-42}, doi = {10.1016/j.pbiomolbio.2019.04.006}, pmid = {31029570}, issn = {1873-1732}, mesh = {Barium/chemistry ; Benzyl Compounds/chemistry ; Biomimetic Materials/*chemistry ; Carbonates/chemistry ; Cell Division ; Cells/*chemistry/*ultrastructure ; Computer Simulation ; Diffusion ; Gibberellins/chemistry ; Models, Biological ; Purines/chemistry ; Quantum Theory ; Silicon Dioxide/chemistry ; Solvents/chemistry ; }, abstract = {Despite decades of focused research, a detailed understanding of the fundamental physical processes that underpin biological systems (structures and processes) remains an open challenge. Within the present paper we report on biomimetic studies, which offer new insights into the process of cell division and the emergence of different cellular and multicellular structures. Experimental studies specifically investigated the impact of including different concentrations of charged bio-molecules (cytokinin and gibberellic acid) on the growth of BaCO3-SiO2 based structures. Results highlighted the role of charge density on the emergence of long-range order, underpinned by a negentropic process. This included the growth of synthetic cell-like structures, with the intrinsic capacity to divide and change morphology at cellular and multicellular scales. Detailed study of dividing structures supports a hypothesis that cell division is dependent on the establishment of a charge-induced macroscopic quantum potential and cell-scale quantum coherence, which allows a description in terms of a macroscopic Schrödinger-like equation, based on a constant different from the Planck constant. Whilst the system does not reflect full correspondence with standard quantum mechanics, many of the phenomena that we typically associate with such a system are recovered. In addition to phenomena normally associated with the Schrödinger equation, we also unexpectedly report on the emergence of intrinsic spin as a macroscopic quantum phenomena, whose origins we account for within a four-dimensional fractal space-time and a macroscopic Pauli equation, which represents the non-relativistic limit of the Dirac equation.}, } @article {pmid31023220, year = {2019}, author = {Krishnan, A and Degnan, BM and Degnan, SM}, title = {The first identification of complete Eph-ephrin signalling in ctenophores and sponges reveals a role for neofunctionalization in the emergence of signalling domains.}, journal = {BMC evolutionary biology}, volume = {19}, number = {1}, pages = {96}, pmid = {31023220}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; Ctenophora/*metabolism ; Ephrins/*metabolism ; Evolution, Molecular ; Humans ; Ligands ; Phylogeny ; Porifera/*metabolism ; Protein Binding ; Protein Domains ; Receptors, Eph Family/chemistry/*metabolism ; *Signal Transduction ; }, abstract = {BACKGROUND: Animals have a greater diversity of signalling pathways than their unicellular relatives, consistent with the evolution and expansion of these pathways occurring in parallel with the origin of animal multicellularity. However, the genomes of sponges and ctenophores - non-bilaterian basal animals - typically encode no, or far fewer, recognisable signalling ligands compared to bilaterians and cnidarians. For instance, the largest subclass of receptor tyrosine kinases (RTKs) in bilaterians, the Eph receptors (Ephs), are present in sponges and ctenophores, but their cognate ligands, the ephrins, have not yet been detected.

RESULTS: Here, we use an iterative HMM analysis to identify for the first time membrane-bound ephrins in sponges and ctenophores. We also expand the number of Eph-receptor subtypes identified in these animals and in cnidarians. Both sequence and structural analyses are consistent with the Eph ligand binding domain (LBD) and the ephrin receptor binding domain (RBD) having evolved via the co-option of ancient galactose-binding (discoidin-domain)-like and monodomain cupredoxin domains, respectively. Although we did not detect a complete Eph-ephrin signalling pathway in closely-related unicellular holozoans or in other non-metazoan eukaryotes, truncated proteins with Eph receptor LBDs and ephrin RBDs are present in some choanoflagellates. Together, these results indicate that Eph-ephrin signalling was present in the last common ancestor of extant metazoans, and perhaps even in the last common ancestor of animals and choanoflagellates. Either scenario pushes the origin of Eph-ephrin signalling back much earlier than previously reported.

CONCLUSIONS: We propose that the Eph-LBD and ephrin-RBD, which were ancestrally localised in the cytosol, became linked to the extracellular parts of two cell surface proteins before the divergence of sponges and ctenophores from the rest of the animal kingdom. The ephrin-RBD lost the ancestral capacity to bind copper, and the Eph-LBD became linked to an ancient RTK. The identification of divergent ephrin ligands in sponges and ctenophores suggests that these ligands evolve faster than their cognate receptors. As this may be a general phenomena, we propose that the sequence-structure approach used in this study may be usefully applied to other signalling systems where no, or a small number of, ligands have been identified.}, } @article {pmid31012964, year = {2019}, author = {Gunaratne, PH and Pan, Y and Rao, AK and Lin, C and Hernandez-Herrera, A and Liang, K and Rait, AS and Venkatanarayan, A and Benham, AL and Rubab, F and Kim, SS and Rajapakshe, K and Chan, CK and Mangala, LS and Lopez-Berestein, G and Sood, AK and Rowat, AC and Coarfa, C and Pirollo, KF and Flores, ER and Chang, EH}, title = {Activating p53 family member TAp63: A novel therapeutic strategy for targeting p53-altered tumors.}, journal = {Cancer}, volume = {125}, number = {14}, pages = {2409-2422}, pmid = {31012964}, issn = {1097-0142}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA160394/CA/NCI NIH HHS/United States ; T32 CA009686/CA/NCI NIH HHS/United States ; R01 CA218025/CA/NCI NIH HHS/United States ; R35 CA197452/CA/NCI NIH HHS/United States ; R01 CA132012/CA/NCI NIH HHS/United States ; R00 DK094981/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; Binding Sites ; Cell Line, Tumor ; Cell Movement/drug effects ; Cisplatin/pharmacology/therapeutic use ; Drug Resistance, Neoplasm/drug effects ; Female ; Humans ; Liposomes ; Mice ; Mice, Nude ; MicroRNAs/administration & dosage/genetics/metabolism/*therapeutic use ; *Mutation, Missense ; Neoplasm Invasiveness/prevention & control ; Ovarian Neoplasms/*drug therapy/*genetics ; Protein Isoforms/genetics ; Signal Transduction/drug effects ; Transcription Factors/*genetics/metabolism ; Transcriptional Activation/*genetics ; Transfection ; Tumor Suppressor Protein p53/*genetics/metabolism ; Tumor Suppressor Proteins/*genetics/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Over 96% of high-grade ovarian carcinomas and 50% of all cancers are characterized by alterations in the p53 gene. Therapeutic strategies to restore and/or reactivate the p53 pathway have been challenging. By contrast, p63, which shares many of the downstream targets and functions of p53, is rarely mutated in cancer.

METHODS: A novel strategy is presented for circumventing alterations in p53 by inducing the tumor-suppressor isoform TAp63 (transactivation domain of tumor protein p63) through its direct downstream target, microRNA-130b (miR-130b), which is epigenetically silenced and/or downregulated in chemoresistant ovarian cancer.

RESULTS: Treatment with miR-130b resulted in: 1) decreased migration/invasion in HEYA8 cells (p53 wild-type) and disruption of multicellular spheroids in OVCAR8 cells (p53-mutant) in vitro, 2) sensitization of HEYA8 and OVCAR8 cells to cisplatin (CDDP) in vitro and in vivo, and 3) transcriptional activation of TAp63 and the B-cell lymphoma (Bcl)-inhibitor B-cell lymphoma 2-like protein 11 (BIM). Overexpression of TAp63 was sufficient to decrease cell viability, suggesting that it is a critical downstream effector of miR-130b. In vivo, combined miR-130b plus CDDP exhibited greater therapeutic efficacy than miR-130b or CDDP alone. Mice that carried OVCAR8 xenograft tumors and were injected with miR-130b in 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) liposomes had a significant decrease in tumor burden at rates similar to those observed in CDDP-treated mice, and 20% of DOPC-miR-130b plus CDDP-treated mice were living tumor free. Systemic injections of scL-miR-130b plus CDDP in a clinically tested, tumor-targeted nanocomplex (scL) improved survival in 60% and complete remissions in 40% of mice that carried HEYA8 xenografts.

CONCLUSIONS: The miR-130b/TAp63 axis is proposed as a new druggable pathway that has the potential to uncover broad-spectrum therapeutic options for the majority of p53-altered cancers.}, } @article {pmid31006855, year = {2019}, author = {Sudianto, E}, title = {Digest: Banding together to battle adversaries has its consequences.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {6}, pages = {1320-1321}, doi = {10.1111/evo.13750}, pmid = {31006855}, issn = {1558-5646}, mesh = {Animals ; *Biological Evolution ; *Chlorella ; Cost-Benefit Analysis ; Predatory Behavior ; }, abstract = {Why did life evolve from single-celled to multicellular organisms? Could there be advantages to this transition? What about associated fitness costs? Kapsetaki and West found that although multicellularity allows Chlorella sorokiniana to avoid predation from similarly-sized predators, it also reduces their competitiveness when resources are limited.}, } @article {pmid31002575, year = {2019}, author = {Lehtonen, J and Parker, GA}, title = {Evolution of the Two Sexes under Internal Fertilization and Alternative Evolutionary Pathways.}, journal = {The American naturalist}, volume = {193}, number = {5}, pages = {702-716}, doi = {10.1086/702588}, pmid = {31002575}, issn = {1537-5323}, mesh = {*Biological Evolution ; *Fertilization ; Germ Cells/*physiology ; *Models, Biological ; *Sex ; Sex Characteristics ; }, abstract = {Transition from isogamy to anisogamy, hence males and females, leads to sexual selection, sexual conflict, sexual dimorphism, and sex roles. Gamete dynamics theory links biophysics of gamete limitation, gamete competition, and resource requirements for zygote survival and assumes broadcast spawning. It makes testable predictions, but most comparative tests use volvocine algae, which feature internal fertilization. We broaden this theory by comparing broadcast-spawning predictions with two plausible internal-fertilization scenarios: gamete casting/brooding (one mating type retains gametes internally, the other broadcasts them) and packet casting/brooding (one type retains gametes internally, the other broadcasts packets containing gametes, which are released for fertilization). Models show that predictions are remarkably robust to these radical changes, yielding (1) isogamy under low gamete limitation, low gamete competition, and similar required resources for gametes and zygotes, (2) anisogamy when gamete competition and/or limitation are higher and when zygotes require more resources than gametes, as is likely as multicellularity develops, (3) a positive correlation between multicellular complexity and anisogamy ratio, and (4) under gamete competition, only brooders becoming female. Thus, gamete dynamics theory represents a potent rationale for isogamy/anisogamy and makes similar testable predictions for broadcast spawners and internal fertilizers, regardless of whether anisogamy or internal fertilization evolved first.}, } @article {pmid31002570, year = {2019}, author = {Olito, C and Connallon, T}, title = {Sexually Antagonistic Variation and the Evolution of Dimorphic Sexual Systems.}, journal = {The American naturalist}, volume = {193}, number = {5}, pages = {688-701}, doi = {10.1086/702847}, pmid = {31002570}, issn = {1537-5323}, mesh = {Alleles ; *Biological Evolution ; Infertility/genetics ; *Models, Biological ; *Sex ; *Sex Characteristics ; }, abstract = {Multicellular Eukaryotes use a broad spectrum of sexual reproduction strategies, ranging from simultaneous hermaphroditism to complete dioecy (separate sexes). The evolutionary pathway from hermaphroditism to dioecy involves the spread of sterility alleles that eliminate female or male reproductive functions, producing unisexual individuals. Classical theory predicts that evolutionary transitions to dioecy are feasible when female and male sex functions genetically trade off with one another (allocation to sex functions is sexually antagonistic) and rates of self-fertilization and inbreeding depression are high within the ancestral hermaphrodite population. We show that genetic linkage between sterility alleles and loci under sexually antagonistic selection significantly alters these classical predictions. We identify three specific consequences of linkage for the evolution of dimorphic sexual systems. First, linkage broadens conditions for the invasion of unisexual sterility alleles, facilitating transitions to sexual systems that are intermediate between hermaphroditism and dioecy (androdioecy and gynodioecy). Second, linkage elevates the equilibrium frequencies of unisexual individuals within androdioecious and gynodioecious populations, which promotes subsequent transitions to full dioecy. Third, linkage dampens the role of inbreeding during transitions to androdioecy and gynodioecy, making these transitions feasible in outbred populations. We discuss implications of these results for the evolution of dimorphic reproductive systems and sex chromosomes.}, } @article {pmid30989827, year = {2019}, author = {Hehmeyer, J}, title = {Two potential evolutionary origins of the fruiting bodies of the dictyostelid slime moulds.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {94}, number = {5}, pages = {1591-1604}, doi = {10.1111/brv.12516}, pmid = {30989827}, issn = {1469-185X}, mesh = {*Biological Evolution ; Dictyostelium/classification/genetics/*physiology ; Fruiting Bodies, Fungal/genetics/*physiology ; Phylogeny ; Spores, Fungal/genetics/physiology ; }, abstract = {Dictyostelium discoideum and the other dictyostelid slime moulds ('social amoebae') are popular model organisms best known for their demonstration of sorocarpic development. In this process, many cells aggregate to form a multicellular unit that ultimately becomes a fruiting body bearing asexual spores. Several other unrelated microorganisms undergo comparable processes, and in some it is evident that their multicellular development evolved from the differentiation process of encystation. While it has been argued that the dictyostelid fruiting body had similar origins, it has also been proposed that dictyostelid sorocarpy evolved from the unicellular fruiting process found in other amoebozoan slime moulds. This paper reviews the developmental biology of the dictyostelids and other relevant organisms and reassesses the two hypotheses on the evolutionary origins of dictyostelid development. Recent advances in phylogeny, genetics, and genomics and transcriptomics indicate that further research is necessary to determine whether or not the fruiting bodies of the dictyostelids and their closest relatives, the myxomycetes and protosporangids, are homologous.}, } @article {pmid30989676, year = {2019}, author = {Ranjbaran, A and Latifi, Z and Nejabati, HR and Abroon, S and Mihanfar, A and Sadigh, AR and Fattahi, A and Nouri, M and Raffel, N}, title = {Exosome-based intercellular communication in female reproductive microenvironments.}, journal = {Journal of cellular physiology}, volume = {234}, number = {11}, pages = {19212-19222}, doi = {10.1002/jcp.28668}, pmid = {30989676}, issn = {1097-4652}, mesh = {Cell Communication/*genetics ; Cellular Microenvironment/genetics ; Drug Delivery Systems ; Exosomes/*genetics ; Female ; *Gene Transfer Techniques ; Genitalia, Female/*metabolism/pathology ; Humans ; Nanoparticles/therapeutic use ; }, abstract = {Different strategies are applied for cellular cross-talk and organization in multicellular organisms. Exosomes are a homogenous population of biological nanoparticles (30-100 nm), originated from multivesicular bodies. The exosomes (Exos) could regulate and affect both cellular physiology and pathophysiology in various organs, such as the female reproductive tract, by altering gene pathways and/or epigenetic programming. Besides, engineered Exos have the potential to be used as a novel drug and gene delivery tools. Here in this review, we discussed various aspects of exosome-based intercellular communication in female reproductive microenvironments. Furthermore, we addressed the findings and issues related to Exos in reproductive biology to give a better view of the involved molecular mechanisms. Moreover, clinical applications of the Exos and their isolation source/methods have been considered to throw some light on the progression of new biological, diagnostic, and therapeutic approaches in clinical embryology.}, } @article {pmid30989357, year = {2020}, author = {Pérez, P and Soto, T and Gómez-Gil, E and Cansado, J}, title = {Functional interaction between Cdc42 and the stress MAPK signaling pathway during the regulation of fission yeast polarized growth.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {23}, number = {1}, pages = {31-41}, doi = {10.1007/s10123-019-00072-6}, pmid = {30989357}, issn = {1618-1905}, support = {BIO2015-69958-P//Ministerio de Economía, Industria y Competitividad, Gobierno de España/ ; BFU2017-82423-P//Ministerio de Economía, Industria y Competitividad, Gobierno de España/ ; CSI068P17//Consejería de Educación, Junta de Castilla y León/ ; CLU-2017-03//Consejería de Educación, Junta de Castilla y León/ ; }, mesh = {Cell Polarity ; *Fungal Proteins ; *MAP Kinase Signaling System ; Phosphorylation ; Protein Binding ; Protein Transport ; Schizosaccharomyces/cytology/*physiology ; *Stress, Physiological ; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae/*metabolism ; }, abstract = {Cell polarization can be defined as the generation and maintenance of directional cellular organization. The spatial distribution and protein or lipid composition of the cell are not symmetric but organized in specialized domains which allow cells to grow and acquire a certain shape that is closely linked to their physiological function. The establishment and maintenance of polarized growth requires the coordination of diverse processes including cytoskeletal dynamics, membrane trafficking, and signaling cascade regulation. Some of the major players involved in the selection and maintenance of sites for polarized growth are Rho GTPases, which recognize the polarization site and transmit the signal to regulatory proteins of the cytoskeleton. Additionally, cytoskeletal organization, polarized secretion, and endocytosis are controlled by signaling pathways including those mediated by mitogen-activated protein kinases (MAPKs). Rho GTPases and the MAPK signaling pathways are strongly conserved from yeast to mammals, suggesting that the basic mechanisms of polarized growth have been maintained throughout evolution. For this reason, the study of how polarized growth is established and regulated in simple organisms such as the fission yeast Schizosaccharomyces pombe has contributed to broaden our knowledge about these processes in multicellular organisms. We review here the function of the Cdc42 GTPase and the stress activated MAPK (SAPK) signaling pathways during fission yeast polarized growth, and discuss the relevance of the crosstalk between both pathways.}, } @article {pmid30980502, year = {2019}, author = {Qian, XX and Liu, J and Menguy, N and Li, J and Alberto, F and Teng, Z and Xiao, T and Zhang, W and Wu, LF}, title = {Identification of novel species of marine magnetotactic bacteria affiliated with Nitrospirae phylum.}, journal = {Environmental microbiology reports}, volume = {11}, number = {3}, pages = {330-337}, doi = {10.1111/1758-2229.12755}, pmid = {30980502}, issn = {1758-2229}, support = {//CNRS/International ; 41522402//NSFC/International ; U1706208//NSFC/International ; 41776131//NSFC/International ; }, mesh = {Bacteria/*classification/cytology/genetics/*metabolism ; Cytoplasm/metabolism ; Locomotion ; Magnetosomes/*metabolism ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sulfur/metabolism ; Water Microbiology ; }, abstract = {Magnetotactic bacteria (MTB) are a group of Gram-negative bacteria characterized by synthesizing magnetosomes and swimming along geomagnetic field lines. Phylogenetically, they belong to different taxonomic lineages including Proteobacteria, Nitrospirae, Omnitrophica, Latescibacteria and Planctomycetes phyla on the phylogenetic tree. To date, six Nitrospirae MTB phylotypes have been identified from freshwater or low-salinity environments and described in the literature. Here, we report the identification of two Nitrospirae MTB phylotypes collected, for the first time, from the marine environment. Both have a spherical morphology with a cell size of ~ 5 μM and similar motility but are different colours (black-brown and ivory-white) under the optic microscope. They synthesized bullet-shaped iron-oxide magnetosomes that were arranged in multiple bundles of chains. Moreover, the cytoplasm of the black-brown Nitrospirae MTB contained sulphur inclusions that conferred on cells a rough, granular appearance. Phylogenetic analysis based on their 16S rRNA gene sequences revealed that they are two novel species and cluster with the previously reported MTB affiliated with the phylum Nitrospirae, thus extending the distribution of Nitrospirae MTB from freshwater to the marine environment.}, } @article {pmid30978201, year = {2019}, author = {Laundon, D and Larson, BT and McDonald, K and King, N and Burkhardt, P}, title = {The architecture of cell differentiation in choanoflagellates and sponge choanocytes.}, journal = {PLoS biology}, volume = {17}, number = {4}, pages = {e3000226}, pmid = {30978201}, issn = {1545-7885}, mesh = {Animals ; Cell Differentiation/genetics ; Choanoflagellata/genetics/metabolism/*physiology ; Microscopy, Electron, Transmission ; Morphogenesis/*physiology ; Phylogeny ; Porifera/genetics/*physiology ; }, abstract = {Although collar cells are conserved across animals and their closest relatives, the choanoflagellates, little is known about their ancestry, their subcellular architecture, or how they differentiate. The choanoflagellate Salpingoeca rosetta expresses genes necessary for animal development and can alternate between unicellular and multicellular states, making it a powerful model for investigating the origin of animal multicellularity and mechanisms underlying cell differentiation. To compare the subcellular architecture of solitary collar cells in S. rosetta with that of multicellular 'rosette' colonies and collar cells in sponges, we reconstructed entire cells in 3D through transmission electron microscopy on serial ultrathin sections. Structural analysis of our 3D reconstructions revealed important differences between single and colonial choanoflagellate cells, with colonial cells exhibiting a more amoeboid morphology consistent with higher levels of macropinocytotic activity. Comparison of multiple reconstructed rosette colonies highlighted the variable nature of cell sizes, cell-cell contact networks, and colony arrangement. Importantly, we uncovered the presence of elongated cells in some rosette colonies that likely represent a distinct and differentiated cell type, pointing toward spatial cell differentiation. Intercellular bridges within choanoflagellate colonies displayed a variety of morphologies and connected some but not all neighbouring cells. Reconstruction of sponge choanocytes revealed ultrastructural commonalities but also differences in major organelle composition in comparison to choanoflagellates. Together, our comparative reconstructions uncover the architecture of cell differentiation in choanoflagellates and sponge choanocytes and constitute an important step in reconstructing the cell biology of the last common ancestor of animals.}, } @article {pmid30967090, year = {2019}, author = {Cotter, SC and Pincheira-Donoso, D and Thorogood, R}, title = {Defences against brood parasites from a social immunity perspective.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1769}, pages = {20180207}, pmid = {30967090}, issn = {1471-2970}, mesh = {Animals ; Biological Evolution ; *Birds/parasitology/physiology ; *Cues ; *Host-Parasite Interactions ; *Insecta/parasitology/physiology ; *Recognition, Psychology ; *Social Behavior ; }, abstract = {Parasitic interactions are so ubiquitous that all multicellular organisms have evolved a system of defences to reduce their costs, whether the parasites they encounter are the classic parasites which feed on the individual, or brood parasites which usurp parental care. Many parallels have been drawn between defences deployed against both types of parasite, but typically, while defences against classic parasites have been selected to protect survival, those against brood parasites have been selected to protect the parent's inclusive fitness, suggesting that the selection pressures they impose are fundamentally different. However, there is another class of defences against classic parasites that have specifically been selected to protect an individual's inclusive fitness, known as social immunity. Social immune responses include the anti-parasite defences typically provided for others in kin-structured groups, such as the antifungal secretions produced by termite workers to protect the brood. Defences against brood parasites, therefore, are more closely aligned with social immune responses. Much like social immunity, host defences against brood parasitism are employed by a donor (a parent) for the benefit of one or more recipients (typically kin), and as with social defences against classic parasites, defences have therefore evolved to protect the donor's inclusive fitness, not the survival or ultimately the fitness of individual recipients This can lead to severe conflicts between the different parties, whose interests are not always aligned. Here, we consider defences against brood parasitism in the light of social immunity, at different stages of parasite encounter, addressing where conflicts occur and how they might be resolved. We finish with considering how this approach could help us to address longstanding questions in our understanding of brood parasitism. This article is part of the theme issue 'The coevolutionary biology of brood parasitism: from mechanism to pattern'.}, } @article {pmid30963641, year = {2019}, author = {Rêgo, A and Messina, FJ and Gompert, Z}, title = {Dynamics of genomic change during evolutionary rescue in the seed beetle Callosobruchus maculatus.}, journal = {Molecular ecology}, volume = {28}, number = {9}, pages = {2136-2154}, doi = {10.1111/mec.15085}, pmid = {30963641}, issn = {1365-294X}, mesh = {Adaptation, Physiological/genetics ; Animals ; Bayes Theorem ; Biological Evolution ; Coleoptera/*genetics ; Gene Frequency ; Genetic Drift ; Genetic Fitness ; Lens Plant ; Linkage Disequilibrium ; Models, Genetic ; Polymorphism, Single Nucleotide ; Seeds ; *Selection, Genetic ; }, abstract = {Rapid adaptation can prevent extinction when populations are exposed to extremely marginal or stressful environments. Factors that affect the likelihood of evolutionary rescue from extinction have been identified, but much less is known about the evolutionary dynamics (e.g., rates and patterns of allele frequency change) and genomic basis of successful rescue, particularly in multicellular organisms. We conducted an evolve-and-resequence experiment to investigate the dynamics of evolutionary rescue at the genetic level in the cowpea seed beetle, Callosobruchus maculatus, when it is experimentally shifted to a stressful host plant, lentil. Low survival (~1%) at the onset of the experiment caused population decline. But adaptive evolution quickly rescued the population, with survival rates climbing to 69% by the F5 generation and 90% by the F10 generation. Population genomic data showed that rescue likely was caused by rapid evolutionary change at multiple loci, with many alleles fixing or nearly fixing within five generations of selection on lentil. Selection on these loci was only moderately consistent in time, but parallel evolutionary changes were evident in sublines formed after the lentil line had passed through a bottleneck. By comparing estimates of selection and genomic change on lentil across five independent C. maculatus lines (the new lentil-adapted line, three long-established lines and one case of failed evolutionary rescue), we found that adaptation on lentil occurred via somewhat idiosyncratic evolutionary changes. Overall, our results suggest that evolutionary rescue in this system can be caused by very strong selection on multiple loci driving rapid and pronounced genomic change.}, } @article {pmid30958167, year = {2019}, author = {Nguyen, H and Koehl, MAR and Oakes, C and Bustamante, G and Fauci, L}, title = {Effects of cell morphology and attachment to a surface on the hydrodynamic performance of unicellular choanoflagellates.}, journal = {Journal of the Royal Society, Interface}, volume = {16}, number = {150}, pages = {20180736}, pmid = {30958167}, issn = {1742-5662}, mesh = {Cell Adhesion/*physiology ; Choanoflagellata/cytology/*physiology ; *Hydrodynamics ; *Models, Biological ; Surface Properties ; Swimming/*physiology ; }, abstract = {Choanoflagellates, eukaryotes that are important predators on bacteria in aquatic ecosystems, are closely related to animals and are used as a model system to study the evolution of animals from protozoan ancestors. The choanoflagellate Salpingoeca rosetta has a complex life cycle with different morphotypes, some unicellular and some multicellular. Here we use computational fluid dynamics to study the hydrodynamics of swimming and feeding by different unicellular stages of S. rosetta: a swimming cell with a collar of prey-capturing microvilli surrounding a single flagellum, a thecate cell attached to a surface and a dispersal-stage cell with a slender body, long flagellum and short collar. We show that a longer flagellum increases swimming speed, longer microvilli reduce speed and cell shape only affects speed when the collar is very short. The flux of prey-carrying water into the collar capture zone is greater for swimming than sessile cells, but this advantage decreases with collar size. Stalk length has little effect on flux for sessile cells. We show that ignoring the collar, as earlier models have done, overestimates flux and greatly overestimates the benefit to feeding performance of swimming versus being attached, and of a longer stalk for attached cells.}, } @article {pmid30952878, year = {2019}, author = {Baade, T and Paone, C and Baldrich, A and Hauck, CR}, title = {Clustering of integrin β cytoplasmic domains triggers nascent adhesion formation and reveals a protozoan origin of the integrin-talin interaction.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {5728}, pmid = {30952878}, issn = {2045-2322}, mesh = {Cytoplasm/*metabolism ; HEK293 Cells ; Humans ; Integrin beta Chains/*metabolism ; Protein Binding ; Talin/*metabolism ; }, abstract = {Integrins and integrin-dependent cell-matrix adhesions are essential for a number of physiological processes. Integrin function is tightly regulated via binding of cytoplasmic proteins to integrin intracellular domains. Yet, the complexity of cell-matrix adhesions in mammals, with more than 150 core adhesome proteins, complicates the analysis of integrin-associated protein complexes. Interestingly, the evolutionary origin of integrins dates back before the transition from unicellular life to complex multicellular animals. Though unicellular relatives of metazoa have a less complex adhesome, nothing is known about the initial steps of integrin activation and adhesion complex assembly in protozoa. Therefore, we developed a minimal, microscope-based system using chimeric integrins to investigate receptor-proximal events during focal adhesion assembly. Clustering of the human integrin β1 tail led to recruitment of talin, kindlin, and paxillin and mutation of the known talin binding site abolished recruitment of this protein. Proteins indirectly linked to integrins, such as vinculin, migfilin, p130[CAS], or zyxin were not enriched around the integrin β1 tail. With the exception of integrin β4 and integrin β8, the cytoplasmic domains of all human integrin β subunits supported talin binding. Likewise, the cytoplasmic domains of integrin β subunits expressed by the protozoan Capsaspora owczarzaki readily recruited talin and this interaction was based on an evolutionary conserved NPXY/F amino acid motif. The results we present here validate the use of our novel microscopic assay to uncover details of integrin-based protein-protein interactions in a cellular context and suggest that talin binding to integrin β cytoplasmic tails is an ancient feature of integrin regulation.}, } @article {pmid30949307, year = {2019}, author = {Bohlin, J and Pettersson, JH}, title = {Evolution of Genomic Base Composition: From Single Cell Microbes to Multicellular Animals.}, journal = {Computational and structural biotechnology journal}, volume = {17}, number = {}, pages = {362-370}, pmid = {30949307}, issn = {2001-0370}, abstract = {Whole genome sequencing (WGS) of thousands of microbial genomes has provided considerable insight into evolutionary mechanisms in the microbial world. While substantially fewer eukaryotic genomes are available for analyses the number is rapidly increasing. This mini-review summarizes broadly evolutionary dynamics of base composition in the different domains of life from the perspective of prokaryotes. Common and different evolutionary mechanisms influencing genomic base composition in eukaryotes and prokaryotes are discussed. The conclusion from the data currently available suggests that while there are similarities there are also striking differences in how genomic base composition has evolved within prokaryotes and eukaryotes. For instance, homologous recombination appears to increase GC content locally in eukaryotes due to a non-selective process termed GC-biased gene conversion (gBGC). For prokaryotes on the other hand, increase in genomic GC content seems to be driven by the environment and selection. We find that similar phenomena observed for some organisms in each respective domain may be caused by very different mechanisms: while gBGC and recombination rates appear to explain the negative correlation between GC3 (GC content based on the third codon nucleotides) and genome size in some eukaryotes uptake of AT rich DNA sequences is the main reason for a similar negative correlation observed in prokaryotes. We provide further examples that indicate that base composition in prokaryotes and eukaryotes have evolved under very different constraints.}, } @article {pmid30941746, year = {2019}, author = {Gulli, JG and Herron, MD and Ratcliff, WC}, title = {Evolution of altruistic cooperation among nascent multicellular organisms.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {5}, pages = {1012-1024}, pmid = {30941746}, issn = {1558-5646}, support = {NNA17BB05A/NASA/NASA/United States ; DGE-1148903//Division of Graduate Education/International ; NNX15AR33G/NASA/NASA/United States ; DEB-1723293//National Science Foundation/International ; NNA17BB05A/ImNASA/Intramural NASA/United States ; }, mesh = {*Biological Evolution ; Cell Death ; Cluster Analysis ; DNA, Fungal/analysis ; Genotype ; Models, Biological ; Yeasts/*genetics/*physiology ; }, abstract = {Cooperation is a classic solution to hostile environments that limit individual survival. In extreme cases this may lead to the evolution of new types of biological individuals (e.g., eusocial super-organisms). We examined the potential for interindividual cooperation to evolve via experimental evolution, challenging nascent multicellular "snowflake yeast" with an environment in which solitary multicellular clusters experienced low survival. In response, snowflake yeast evolved to form cooperative groups composed of thousands of multicellular clusters that typically survive selection. Group formation occurred through the creation of protein aggregates, only arising in strains with high (>2%) rates of cell death. Nonetheless, it was adaptive and repeatable, although ultimately evolutionarily unstable. Extracellular protein aggregates act as a common good, as they can be exploited by cheats that do not contribute to aggregate production. These results highlight the importance of group formation as a mechanism for surviving environmental stress, and underscore the remarkable ease with which even simple multicellular entities may evolve-and lose-novel social traits.}, } @article {pmid30925871, year = {2019}, author = {Kim, HM and Weber, JA and Lee, N and Park, SG and Cho, YS and Bhak, Y and Lee, N and Jeon, Y and Jeon, S and Luria, V and Karger, A and Kirschner, MW and Jo, YJ and Woo, S and Shin, K and Chung, O and Ryu, JC and Yim, HS and Lee, JH and Edwards, JS and Manica, A and Bhak, J and Yum, S}, title = {The genome of the giant Nomura's jellyfish sheds light on the early evolution of active predation.}, journal = {BMC biology}, volume = {17}, number = {1}, pages = {28}, pmid = {30925871}, issn = {1741-7007}, support = {R01 HD073104/HD/NICHD NIH HHS/United States ; R01 HD091846/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; *Evolution, Molecular ; Genome/*physiology ; Phylogeny ; *Predatory Behavior ; Scyphozoa/genetics/*physiology ; }, abstract = {BACKGROUND: Unique among cnidarians, jellyfish have remarkable morphological and biochemical innovations that allow them to actively hunt in the water column and were some of the first animals to become free-swimming. The class Scyphozoa, or true jellyfish, are characterized by a predominant medusa life-stage consisting of a bell and venomous tentacles used for hunting and defense, as well as using pulsed jet propulsion for mobility. Here, we present the genome of the giant Nomura's jellyfish (Nemopilema nomurai) to understand the genetic basis of these key innovations.

RESULTS: We sequenced the genome and transcriptomes of the bell and tentacles of the giant Nomura's jellyfish as well as transcriptomes across tissues and developmental stages of the Sanderia malayensis jellyfish. Analyses of the Nemopilema and other cnidarian genomes revealed adaptations associated with swimming, marked by codon bias in muscle contraction and expansion of neurotransmitter genes, along with expanded Myosin type II family and venom domains, possibly contributing to jellyfish mobility and active predation. We also identified gene family expansions of Wnt and posterior Hox genes and discovered the important role of retinoic acid signaling in this ancient lineage of metazoans, which together may be related to the unique jellyfish body plan (medusa formation).

CONCLUSIONS: Taken together, the Nemopilema jellyfish genome and transcriptomes genetically confirm their unique morphological and physiological traits, which may have contributed to the success of jellyfish as early multi-cellular predators.}, } @article {pmid30923125, year = {2019}, author = {Pedchenko, V and Bauer, R and Pokidysheva, EN and Al-Shaer, A and Forde, NR and Fidler, AL and Hudson, BG and Boudko, SP}, title = {A chloride ring is an ancient evolutionary innovation mediating the assembly of the collagen IV scaffold of basement membranes.}, journal = {The Journal of biological chemistry}, volume = {294}, number = {20}, pages = {7968-7981}, pmid = {30923125}, issn = {1083-351X}, support = {R01 DK018381/DK/NIDDK NIH HHS/United States ; R25 DK096999/DK/NIDDK NIH HHS/United States ; T32 DK007569/DK/NIDDK NIH HHS/United States ; }, mesh = {Collagen Type IV/*chemistry ; Crystallography, X-Ray ; Humans ; *Models, Molecular ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; }, abstract = {Collagen IV scaffold is a principal component of the basement membrane (BM), a specialized extracellular matrix that is essential for animal multicellularity and tissue evolution. Scaffold assembly begins with the trimerization of α-chains into protomers inside the cell, which then are secreted and undergo oligomerization outside the cell. For the ubiquitous scaffold composed of α1- and α2-chains, both intracellular and extracellular stages are mediated by the noncollagenous domain (NC1). The association of protomers is chloride-dependent, whereby chloride ions induce interactions of the protomers' trimeric NC1 domains leading to NC1 hexamer formation. Here, we investigated the mechanisms, kinetics, and functionality of the chloride ion-mediated protomer assembly by using a single-chain technology to produce a stable NC1 trimer comprising α1, α2, and α1 NC1 monomers. We observed that in the presence of chloride, the single-chain NC1-trimer self-assembles into a hexamer, for which the crystal structure was determined. We discovered that a chloride ring, comprising 12 ions, induces the assembly of and stabilizes the NC1 hexamer. Furthermore, we found that the chloride ring is evolutionarily conserved across all animals, first appearing in cnidarians. These findings reveal a fundamental role for the chloride ring in the assembly of collagen IV scaffolds of BMs, a critical event enabling tissue evolution and development. Moreover, the single-chain technology is foundational for generating trimeric NC1 domains of other α-chain compositions to investigate the α121, α345, and α565 collagen IV scaffolds and to develop therapies for managing Alport syndrome, Goodpasture's disease, and cancerous tumor growth.}, } @article {pmid30919568, year = {2020}, author = {Zhu, SQ and Zhang, YJ and Abbas, MN and Hao, XW and Zhao, YZ and Liang, HH and Cui, HJ and Yang, LQ}, title = {Hedgehog promotes cell proliferation in the midgut of silkworm, Bombyx mori.}, journal = {Insect science}, volume = {27}, number = {4}, pages = {697-707}, doi = {10.1111/1744-7917.12672}, pmid = {30919568}, issn = {1744-7917}, support = {No. XDJK2015C129//Fundamental Research Funds for the Central Universities/ ; No. 2362015XK09//Fundamental Research Funds for the Central Universities/ ; No. XDJK2013B020//Fundamental Research Funds for the Central Universities/ ; No. 20120524//Fundamental Research Funds for the Central Universities/ ; CXTDX201601010//Chongqing University Innovation Team Building Program funded projects/ ; 2017ZBX10//Scientific Research Foundation of the Chongqing University of Arts and Sciences/ ; No. 31672496//National Natural Science Foundation of China/ ; cstc2016jcyjA0425//Natural Science Foundation of Chongqing/ ; XDJK2015C129//Fundamental Research Funds for the Central Universities/ ; 2362015XK09//Fundamental Research Funds for the Central Universities/ ; XDJK2013B020//Fundamental Research Funds for the Central Universities/ ; 20120524//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; Bombyx/genetics/growth & development/*physiology ; Cell Proliferation/*genetics ; Digestive System/metabolism ; Hedgehog Proteins/*genetics/metabolism ; Larva/genetics/growth & development/metabolism ; }, abstract = {The Hedgehog (Hh) signaling pathway is one of the major regulators of embryonic development and tissue homeostasis in multicellular organisms. However, the role of this pathway in the silkworm, especially in the silkworm midgut, remains poorly understood. Here, we report that Bombyx mori Hedgehog (BmHh) is expressed in most tissues of silkworm larvae and that its functions are well-conserved throughout evolution. We further demonstrate that the messenger RNA of four Hh signaling components, BmHh ligand, BmPtch receptor, signal transducer BmSmo and transcription factor BmCi, are all upregulated following Escherichia coli or Bacillus thuringiensis infection, indicating the activation of the Hh pathway. Simultaneously, midgut cell proliferation is strongly promoted. Conversely, the repression of Hh signal transduction with double-stranded RNA or cyclopamine inhibits the expression of BmHh and BmCi and reduces cell proliferation. Overall, these findings provide new insights into the Hh signaling pathway in the silkworm, B. mori.}, } @article {pmid30919490, year = {2019}, author = {Marshall, RC and Whitworth, DE}, title = {Is "Wolf-Pack" Predation by Antimicrobial Bacteria Cooperative? Cell Behaviour and Predatory Mechanisms Indicate Profound Selfishness, Even when Working Alongside Kin.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {41}, number = {4}, pages = {e1800247}, doi = {10.1002/bies.201800247}, pmid = {30919490}, issn = {1521-1878}, mesh = {Anti-Bacterial Agents/*metabolism ; Biological Evolution ; Models, Biological ; Myxococcales/*cytology ; Time Factors ; }, abstract = {For decades, myxobacteria have been spotlighted as exemplars of social "wolf-pack" predation, communally secreting antimicrobial substances into the shared public milieu. This behavior has been described as cooperative, becoming more efficient if performed by more cells. However, laboratory evidence for cooperativity is limited and of little relevance to predation in a natural setting. In contrast, there is accumulating evidence for predatory mechanisms promoting "selfish" behavior during predation, which together with conflicting definitions of cooperativity, casts doubt on whether microbial "wolf-pack" predation really is cooperative. Here, it is hypothesized that public-goods-mediated predation is not cooperative, and it is argued that a holistic model of microbial predation is needed, accounting for predator and prey relatedness, social phenotypes, spatial organization, activity/specificity/transport of secreted toxins, and prey resistance mechanisms. Filling such gaps in our knowledge is vital if the evolutionary benefits of potentially costly microbial behaviors mediated by public goods are to be properly understood.}, } @article {pmid30918953, year = {2019}, author = {Arimoto, A and Nishitsuji, K and Higa, Y and Arakaki, N and Hisata, K and Shinzato, C and Satoh, N and Shoguchi, E}, title = {A siphonous macroalgal genome suggests convergent functions of homeobox genes in algae and land plants.}, journal = {DNA research : an international journal for rapid publication of reports on genes and genomes}, volume = {26}, number = {2}, pages = {183-192}, pmid = {30918953}, issn = {1756-1663}, mesh = {Caulerpa/*genetics ; Chlorophyta/genetics ; Embryophyta/genetics ; *Evolution, Molecular ; Gene Expression Profiling ; Genes, Homeobox/*genetics ; *Genome, Plant ; Genomics ; *Phylogeny ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; }, abstract = {Genome evolution and development of unicellular, multinucleate macroalgae (siphonous algae) are poorly known, although various multicellular organisms have been studied extensively. To understand macroalgal developmental evolution, we assembled the ∼26 Mb genome of a siphonous green alga, Caulerpa lentillifera, with high contiguity, containing 9,311 protein-coding genes. Molecular phylogeny using 107 nuclear genes indicates that the diversification of the class Ulvophyceae, including C. lentillifera, occurred before the split of the Chlorophyceae and Trebouxiophyceae. Compared with other green algae, the TALE superclass of homeobox genes, which expanded in land plants, shows a series of lineage-specific duplications in this siphonous macroalga. Plant hormone signalling components were also expanded in a lineage-specific manner. Expanded transport regulators, which show spatially different expression, suggest that the structural patterning strategy of a multinucleate cell depends on diversification of nuclear pore proteins. These results not only imply functional convergence of duplicated genes among green plants, but also provide insight into evolutionary roots of green plants. Based on the present results, we propose cellular and molecular mechanisms involved in the structural differentiation in the siphonous alga.}, } @article {pmid30918448, year = {2019}, author = {Stucky, BJ and Balhoff, JP and Barve, N and Barve, V and Brenskelle, L and Brush, MH and Dahlem, GA and Gilbert, JDJ and Kawahara, AY and Keller, O and Lucky, A and Mayhew, PJ and Plotkin, D and Seltmann, KC and Talamas, E and Vaidya, G and Walls, R and Yoder, M and Zhang, G and Guralnick, R}, title = {Developing a vocabulary and ontology for modeling insect natural history data: example data, use cases, and competency questions.}, journal = {Biodiversity data journal}, volume = {7}, number = {}, pages = {e33303}, pmid = {30918448}, issn = {1314-2828}, abstract = {Insects are possibly the most taxonomically and ecologically diverse class of multicellular organisms on Earth. Consequently, they provide nearly unlimited opportunities to develop and test ecological and evolutionary hypotheses. Currently, however, large-scale studies of insect ecology, behavior, and trait evolution are impeded by the difficulty in obtaining and analyzing data derived from natural history observations of insects. These data are typically highly heterogeneous and widely scattered among many sources, which makes developing robust information systems to aggregate and disseminate them a significant challenge. As a step towards this goal, we report initial results of a new effort to develop a standardized vocabulary and ontology for insect natural history data. In particular, we describe a new database of representative insect natural history data derived from multiple sources (but focused on data from specimens in biological collections), an analysis of the abstract conceptual areas required for a comprehensive ontology of insect natural history data, and a database of use cases and competency questions to guide the development of data systems for insect natural history data. We also discuss data modeling and technology-related challenges that must be overcome to implement robust integration of insect natural history data.}, } @article {pmid30915518, year = {2019}, author = {Kolasa, M and Ścibior, R and Mazur, MA and Kubisz, D and Dudek, K and Kajtoch, Ł}, title = {How Hosts Taxonomy, Trophy, and Endosymbionts Shape Microbiome Diversity in Beetles.}, journal = {Microbial ecology}, volume = {78}, number = {4}, pages = {995-1013}, pmid = {30915518}, issn = {1432-184X}, support = {DEC-2013/11/D/NZ8/00583//National Science Centre, Poland/ ; small grants for young researchers//Polish Ministry of Science and Higher Education/ ; }, mesh = {Animals ; Bacteria/*classification ; Bacterial Physiological Phenomena ; Coleoptera/classification/*microbiology/*physiology ; Feeding Behavior ; Microbiota/*physiology ; Phylogeny ; *Symbiosis ; }, abstract = {Bacterial communities play a crucial role in the biology, ecology, and evolution of multicellular organisms. In this research, the microbiome of 24 selected beetle species representing five families (Carabidae, Staphylinidae, Curculionidae, Chrysomelidae, Scarabaeidae) and three trophic guilds (carnivorous, herbivorous, detrivorous) was examined using 16S rDNA sequencing on the Illumina platform. The aim of the study was to compare diversity within and among species on various levels of organization, including evaluation of the impact of endosymbiotic bacteria. Collected data showed that beetles possess various bacterial communities and that microbiota of individuals of particular species hosts are intermixed. The most diverse microbiota were found in Carabidae and Scarabaeidae; the least diverse, in Staphylinidae. On higher organization levels, the diversity of bacteria was more dissimilar between families, while the most distinct with respect to their microbiomes were trophic guilds. Moreover, eight taxa of endosymbiotic bacteria were detected including common genera such as Wolbachia, Rickettsia, and Spiroplasma, as well as the rarely detected Cardinium, Arsenophonus, Buchnera, Sulcia, Regiella, and Serratia. There were no correlations among the abundance of the most common Wolbachia and Rickettsia; a finding that does not support the hypothesis that these bacteria occur interchangeably. The abundance of endosymbionts only weakly and negatively correlates with diversity of the whole microbiome in beetles. Overall, microbiome diversity was found to be more dependent on host phylogeny than on the abundance of endosymbionts. This is the first study in which bacteria diversity is compared between numerous species of beetles in a standardized manner.}, } @article {pmid30915345, year = {2019}, author = {Zannier, F and Portero, LR and Ordoñez, OF and Martinez, LJ and Farías, ME and Albarracin, VH}, title = {Polyextremophilic Bacteria from High Altitude Andean Lakes: Arsenic Resistance Profiles and Biofilm Production.}, journal = {BioMed research international}, volume = {2019}, number = {}, pages = {1231975}, pmid = {30915345}, issn = {2314-6141}, mesh = {Acinetobacter/drug effects/genetics/*growth & development ; Adaptation, Physiological/*genetics ; Altitude ; Arsenic/toxicity ; Biodegradation, Environmental ; Biofilms/drug effects/growth & development ; *Ecosystem ; Lakes/microbiology ; *Phylogeny ; Ultraviolet Rays ; }, abstract = {High levels of arsenic present in the High Altitude Andean Lakes (HAALs) ecosystems selected arsenic-resistant microbial communities which are of novel interest to study adaptations mechanisms potentially useful in bioremediation processes. We herein performed a detailed characterization of the arsenic tolerance profiles and the biofilm production of two HAAL polyextremophiles, Acinetobacter sp. Ver3 (Ver3) and Exiguobacterium sp. S17 (S17). Cellular adherence over glass and polypropylene surfaces were evaluated together with the effect of increasing doses and oxidative states of arsenic over the quality and quantity of their biofilm production. The arsenic tolerance outcomes showed that HAAL strains could tolerate higher arsenic concentrations than phylogenetic related strains belonging to the German collection of microorganisms and cell cultures (Deutsche Sammlung von Mikroorganismen und Zellkulturen, DSMZ), which suggest adaptations of HAAL strains to their original environment. On the other hand, the crystal violet method (CV) and SEM analysis showed that Ver3 and S17 were able to attach to solid surfaces and to form the biofilm. The quantification of biofilms production in 48 hours' cultures through CV shows that Ver3 yielded higher production in the treatment without arsenic cultured on a glass support, while S17 yield higher biofilm production under intermediate arsenic concentration on glass supports. Polypropylene supports had negative effects on the biofilm production of Ver3 and S17. SEM analysis shows that the highest biofilm yields could be associated with a larger number of attached cells as well as the development of more complex 3D multicellular structures.}, } @article {pmid30912879, year = {2019}, author = {Aripovsky, AV and Titov, VN}, title = {[Biologocally active peptides in metabolism regulation. Peptons, peptides, amino acids, fatty acids, lipoproteins, lipids, and the effect of nutriceuticals.].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {64}, number = {1}, pages = {14-23}, doi = {10.18821/0869-2084-2019-64-1-14-23}, pmid = {30912879}, issn = {0869-2084}, mesh = {Amino Acids ; Animals ; Dietary Proteins/metabolism ; *Dietary Supplements ; Fatty Acids ; Humans ; Lipids ; Lipoproteins ; Lysosomes ; Peptides/*metabolism ; Phylogeny ; Proteolysis ; }, abstract = {According to phylogenetic theory of general pathology, formation of multicellular organisms started when each cell (a unicellular organism) reached the first level of relative biological perfection. By that time the stimuli for perfection of the unicellular exhausted, and formation of the multicellular became a biological necessity. All cells, being associated, formed the second level of relative biological perfection within the principle of biological succession. The association included highly organized unicellular organisms with their specific autocrine biological functions and reactions. At the second level of relative biological perfection all humoral mediators in paracrine regulated cell communities (PC) and organs were predominantly hydrophilic and short living. They had a small molecular weight and were probably biologically active peptides (BAP). We believe that functional difference of PC and later of organs is based on differentiation of lysosomal function and production of various enzymes involved in proteolysis of dietary proteins. This allowed various PC and organs to form chemically and functionally different BAP pools from one protein upon proteolysis. Individual peptide pools in PC created the basis for morphologically and functionally different cells and organs. Cell that produces peptides can modify their concentration, chemical parameters and ratios by varying the selectivity of its proteases. In vivo regulation of metabolism by BAP has a common root in bacteria, plants and vertebrates, including Homo sapiens. The third level of relative biological perfection in the organism has formed in close association with cognitive biological function.}, } @article {pmid30912270, year = {2019}, author = {Hamant, O and Bhat, R and Nanjundiah, V and Newman, SA}, title = {Does resource availability help determine the evolutionary route to multicellularity?.}, journal = {Evolution & development}, volume = {21}, number = {3}, pages = {115-119}, pmid = {30912270}, issn = {1525-142X}, support = {ICTS/Prog-LivingMatter2018/04//International Centre for Theoretical Sciences (ICTS)/International ; ERC-2013-CoG-615739 "MechanoDevo"/ERC_/European Research Council/International ; 0412//CSIR/International ; 1586//SERB DST Early Career Grant/International ; }, mesh = {Animals ; *Biological Evolution ; *Gene Expression Regulation, Developmental ; *Genetic Variation ; }, abstract = {Genetic heterogeneity and homogeneity are associated with distinct sets of adaptive advantages and bottlenecks, both in developmental biology and population genetics. Whereas populations of individuals are usually genetically heterogeneous, most multicellular metazoans are genetically homogeneous. Observing that resource scarcity fuels genetic heterogeneity in populations, we propose that monoclonal development is compatible with the resource-rich and stable internal environments that complex multicellular bodies offer. In turn, polyclonal development persists in tumors and in certain metazoans, both exhibiting a closer dependence on external resources. This eco-evo-devo approach also suggests that multicellularity may originally have emerged through polyclonal development in early metazoans, because of their reduced shielding from environmental fluctuations.}, } @article {pmid30911363, year = {2019}, author = {Bielska, E and Birch, PRJ and Buck, AH and Abreu-Goodger, C and Innes, RW and Jin, H and Pfaffl, MW and Robatzek, S and Regev-Rudzki, N and Tisserant, C and Wang, S and Weiberg, A}, title = {Highlights of the mini-symposium on extracellular vesicles in inter-organismal communication, held in Munich, Germany, August 2018.}, journal = {Journal of extracellular vesicles}, volume = {8}, number = {1}, pages = {1590116}, pmid = {30911363}, issn = {2001-3078}, abstract = {All living organisms secrete molecules for intercellular communication. Recent research has revealed that extracellular vesicles (EVs) play an important role in inter-organismal cell-to-cell communication by transporting diverse messenger molecules, including RNA, DNA, lipids and proteins. These discoveries have raised fundamental questions regarding EV biology. How are EVs biosynthesized and loaded with messenger/cargo molecules? How are EVs secreted into the extracellular matrix? What are the EV uptake mechanisms of recipient cells? As EVs are produced by all kind of organisms, from unicellular bacteria and protists, filamentous fungi and oomycetes, to complex multicellular life forms such as plants and animals, basic research in diverse model systems is urgently needed to shed light on the multifaceted biology of EVs and their role in inter-organismal communications. To help catalyse progress in this emerging field, a mini-symposium was held in Munich, Germany in August 2018. This report highlights recent progress and major questions being pursued across a very diverse group of model systems, all united by the question of how EVs contribute to inter-organismal communication.}, } @article {pmid30909510, year = {2019}, author = {Moffitt, L and Karimnia, N and Stephens, A and Bilandzic, M}, title = {Therapeutic Targeting of Collective Invasion in Ovarian Cancer.}, journal = {International journal of molecular sciences}, volume = {20}, number = {6}, pages = {}, pmid = {30909510}, issn = {1422-0067}, mesh = {Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; *Biomarkers, Tumor ; Clinical Studies as Topic ; Disease Management ; Drug Evaluation, Preclinical ; Female ; Humans ; *Molecular Targeted Therapy/methods ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Neoplastic Stem Cells/drug effects/metabolism/pathology ; Ovarian Neoplasms/*etiology/pathology/*therapy ; Standard of Care ; Treatment Outcome ; }, abstract = {Ovarian cancer is the seventh most commonly diagnosed cancer amongst women and has the highest mortality rate of all gynaecological malignancies. It is a heterogeneous disease attributed to one of three cell types found within the reproductive milieu: epithelial, stromal, and germ cell. Each histotype differs in etiology, pathogenesis, molecular biology, risk factors, and prognosis. Furthermore, the origin of ovarian cancer remains unclear, with ovarian involvement secondary to the contribution of other gynaecological tissues. Despite these complexities, the disease is often treated as a single entity, resulting in minimal improvement to survival rates since the introduction of platinum-based chemotherapy over 30 years ago. Despite concerted research efforts, ovarian cancer remains one of the most difficult cancers to detect and treat, which is in part due to the unique mode of its dissemination. Ovarian cancers tend to invade locally to neighbouring tissues by direct extension from the primary tumour, and passively to pelvic and distal organs within the peritoneal fluid or ascites as multicellular spheroids. Once at their target tissue, ovarian cancers, like most epithelial cancers including colorectal, melanoma, and breast, tend to invade as a cohesive unit in a process termed collective invasion, driven by specialized cells termed "leader cells". Emerging evidence implicates leader cells as essential drivers of collective invasion and metastasis, identifying collective invasion and leader cells as a viable target for the management of metastatic disease. However, the development of targeted therapies specifically against this process and this subset of cells is lacking. Here, we review our understanding of metastasis, collective invasion, and the role of leader cells in ovarian cancer. We will discuss emerging research into the development of novel therapies targeting collective invasion and the leader cell population.}, } @article {pmid30904636, year = {2019}, author = {Setia, H and Muotri, AR}, title = {Brain organoids as a model system for human neurodevelopment and disease.}, journal = {Seminars in cell & developmental biology}, volume = {95}, number = {}, pages = {93-97}, pmid = {30904636}, issn = {1096-3634}, support = {R01 MH108528/MH/NIMH NIH HHS/United States ; R01 MH100175/MH/NIMH NIH HHS/United States ; R01 MH094753/MH/NIMH NIH HHS/United States ; R01 MH109885/MH/NIMH NIH HHS/United States ; R56 MH109587/MH/NIMH NIH HHS/United States ; }, mesh = {Brain/drug effects/*embryology/virology ; Environmental Pollutants/toxicity ; Humans ; *Models, Biological ; Nervous System Diseases/genetics/*pathology ; Organoids/drug effects/*embryology ; Viruses/metabolism ; }, abstract = {The ability to reproduce early stages of human neurodevelopment in the laboratory is one of the most exciting fields in modern neuroscience. The inaccessibility of the healthy human brain developing in utero has delayed our understanding of the initial steps in the formation of one of the most complex tissues in the body. Animal models, postmortem human tissues and cellular systems have been instrumental in contributing to our understanding of the human brain. However, all model systems have intrinsic limitations. The emerging field of brain organoids, which are three-dimensional self-assembled multicellular structures derived from human pluripotent stem cells, offers a promising complementary cellular model for the study of the human brain. Here, we will discuss the initial experiments that were the foundation for this emerging field, highlight recent uses of the technology and offer our perspective on future directions that might guide further exploratory experimentation to improve the human brain organoid model system.}, } @article {pmid30902897, year = {2019}, author = {Krizsán, K and Almási, É and Merényi, Z and Sahu, N and Virágh, M and Kószó, T and Mondo, S and Kiss, B and Bálint, B and Kües, U and Barry, K and Cseklye, J and Hegedüs, B and Henrissat, B and Johnson, J and Lipzen, A and Ohm, RA and Nagy, I and Pangilinan, J and Yan, J and Xiong, Y and Grigoriev, IV and Hibbett, DS and Nagy, LG}, title = {Transcriptomic atlas of mushroom development reveals conserved genes behind complex multicellularity in fungi.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {15}, pages = {7409-7418}, pmid = {30902897}, issn = {1091-6490}, mesh = {*Agaricales/genetics/growth & development ; *Databases, Nucleic Acid ; *Fruiting Bodies, Fungal/genetics/growth & development ; *Fungal Proteins/biosynthesis/genetics ; Gene Expression Regulation, Fungal/physiology ; *Genes, Fungal ; Transcriptome/*physiology ; }, abstract = {The evolution of complex multicellularity has been one of the major transitions in the history of life. In contrast to simple multicellular aggregates of cells, it has evolved only in a handful of lineages, including animals, embryophytes, red and brown algae, and fungi. Despite being a key step toward the evolution of complex organisms, the evolutionary origins and the genetic underpinnings of complex multicellularity are incompletely known. The development of fungal fruiting bodies from a hyphal thallus represents a transition from simple to complex multicellularity that is inducible under laboratory conditions. We constructed a reference atlas of mushroom formation based on developmental transcriptome data of six species and comparisons of >200 whole genomes, to elucidate the core genetic program of complex multicellularity and fruiting body development in mushroom-forming fungi (Agaricomycetes). Nearly 300 conserved gene families and >70 functional groups contained developmentally regulated genes from five to six species, covering functions related to fungal cell wall remodeling, targeted protein degradation, signal transduction, adhesion, and small secreted proteins (including effector-like orphan genes). Several of these families, including F-box proteins, expansin-like proteins, protein kinases, and transcription factors, showed expansions in Agaricomycetes, many of which convergently expanded in multicellular plants and/or animals too, reflecting convergent solutions to genetic hurdles imposed by complex multicellularity among independently evolved lineages. This study provides an entry point to studying mushroom development and complex multicellularity in one of the largest clades of complex eukaryotic organisms.}, } @article {pmid30898932, year = {2019}, author = {Wielgoss, S and Wolfensberger, R and Sun, L and Fiegna, F and Velicer, GJ}, title = {Social genes are selection hotspots in kin groups of a soil microbe.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6433}, pages = {1342-1345}, doi = {10.1126/science.aar4416}, pmid = {30898932}, issn = {1095-9203}, mesh = {Alleles ; *Evolution, Molecular ; *Genes, Bacterial ; Microbial Interactions/*genetics ; Myxococcus xanthus/*genetics ; Nucleotidyltransferases/genetics ; Phenotype ; *Selection, Genetic ; *Soil Microbiology ; }, abstract = {The composition of cooperative systems, including animal societies, organismal bodies, and microbial groups, reflects their past and shapes their future evolution. However, genomic diversity within many multiunit systems remains uncharacterized, limiting our ability to understand and compare their evolutionary character. We have analyzed genomic and social-phenotype variation among 120 natural isolates of the cooperative bacterium Myxococcus xanthus derived from six multicellular fruiting bodies. Each fruiting body was composed of multiple lineages radiating from a unique recent ancestor. Genomic evolution was concentrated in selection hotspots associated with evolutionary change in social phenotypes. Synonymous mutations indicated that kin lineages within the same fruiting body often first diverged from a common ancestor more than 100 generations ago. Thus, selection appears to promote endemic diversification of kin lineages that remain together over long histories of local interaction, thereby potentiating social coevolution.}, } @article {pmid30890741, year = {2019}, author = {Eilenberger, C and Rothbauer, M and Ehmoser, EK and Ertl, P and Küpcü, S}, title = {Effect of Spheroidal Age on Sorafenib Diffusivity and Toxicity in a 3D HepG2 Spheroid Model.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {4863}, pmid = {30890741}, issn = {2045-2322}, mesh = {*Cell Culture Techniques ; Cell Survival/*drug effects ; Hep G2 Cells ; Humans ; Sorafenib/*chemistry/toxicity ; Spheroids, Cellular/*drug effects ; }, abstract = {The enhanced predictive power of 3D multi-cellular spheroids in comparison to conventional monolayer cultures makes them a promising drug screening tool. However, clinical translation for pharmacology and toxicology is lagging its technological progression. Even though spheroids show a biological complexity resembling native tissue, standardization and validation of drug screening protocols are influenced by continuously changing physiological parameters during spheroid formation. Such cellular heterogeneities impede the comparability of drug efficacy studies and toxicological screenings. In this paper, we demonstrated that aside from already well-established physiological parameters, spheroidal age is an additional critical parameter that impacts drug diffusivity and toxicity in 3D cell culture models. HepG2 spheroids were generated and maintained on a self-assembled ultra-low attachment nanobiointerface and characterized regarding time-dependent changes in morphology, functionality as well as anti-cancer drug resistance. We demonstrated that spheroidal aging directly influences drug response due to the evolution of spheroid micro-structure and organo-typic functions, that alter inward diffusion, thus drug uptake.}, } @article {pmid30886348, year = {2019}, author = {Talbert, PB and Meers, MP and Henikoff, S}, title = {Old cogs, new tricks: the evolution of gene expression in a chromatin context.}, journal = {Nature reviews. Genetics}, volume = {20}, number = {5}, pages = {283-297}, pmid = {30886348}, issn = {1471-0064}, mesh = {Animals ; Biological Evolution ; *Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone/genetics/history/metabolism ; DNA/*genetics/history/metabolism ; Eukaryotic Cells/cytology/metabolism ; *Genome ; Genomics/methods ; Histones/genetics/history/metabolism ; History, 21st Century ; History, Ancient ; Humans ; Nucleosomes/chemistry/*genetics/metabolism ; Prokaryotic Cells/cytology/metabolism ; Transcription Factors/genetics/history/metabolism ; *Transcription, Genetic ; }, abstract = {Sophisticated gene-regulatory mechanisms probably evolved in prokaryotes billions of years before the emergence of modern eukaryotes, which inherited the same basic enzymatic machineries. However, the epigenomic landscapes of eukaryotes are dominated by nucleosomes, which have acquired roles in genome packaging, mitotic condensation and silencing parasitic genomic elements. Although the molecular mechanisms by which nucleosomes are displaced and modified have been described, just how transcription factors, histone variants and modifications and chromatin regulators act on nucleosomes to regulate transcription is the subject of considerable ongoing study. We explore the extent to which these transcriptional regulatory components function in the context of the evolutionarily ancient role of chromatin as a barrier to processes acting on DNA and how chromatin proteins have diversified to carry out evolutionarily recent functions that accompanied the emergence of differentiation and development in multicellular eukaryotes.}, } @article {pmid30886148, year = {2019}, author = {Xu, S and Stapley, J and Gablenz, S and Boyer, J and Appenroth, KJ and Sree, KS and Gershenzon, J and Widmer, A and Huber, M}, title = {Low genetic variation is associated with low mutation rate in the giant duckweed.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {1243}, pmid = {30886148}, issn = {2041-1723}, mesh = {Africa ; Americas ; Araceae/classification/*genetics ; Asia ; DNA Mutational Analysis ; Europe ; *Genetic Variation ; *Genome, Plant ; *Mutation Rate ; Phylogeography ; Plant Dispersal/*genetics ; }, abstract = {Mutation rate and effective population size (Ne) jointly determine intraspecific genetic diversity, but the role of mutation rate is often ignored. Here we investigate genetic diversity, spontaneous mutation rate and Ne in the giant duckweed (Spirodela polyrhiza). Despite its large census population size, whole-genome sequencing of 68 globally sampled individuals reveals extremely low intraspecific genetic diversity. Assessed under natural conditions, the genome-wide spontaneous mutation rate is at least seven times lower than estimates made for other multicellular eukaryotes, whereas Ne is large. These results demonstrate that low genetic diversity can be associated with large-Ne species, where selection can reduce mutation rates to very low levels. This study also highlights that accurate estimates of mutation rate can help to explain seemingly unexpected patterns of genome-wide variation.}, } @article {pmid30883720, year = {2019}, author = {Kapsetaki, SE and West, SA}, title = {The costs and benefits of multicellular group formation in algae.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {6}, pages = {1296-1308}, doi = {10.1111/evo.13712}, pmid = {30883720}, issn = {1558-5646}, support = {//Alexander S. Onassis Public Benefit Foundation/International ; /ERC_/European Research Council/International ; //A.G. Leventis Foundation/International ; }, mesh = {Animals ; Biological Evolution ; Chlorella/*physiology ; Cost-Benefit Analysis ; Daphnia/*physiology ; *Food Chain ; *Life History Traits ; Microbial Interactions ; Ochromonas/*physiology ; *Predatory Behavior ; }, abstract = {The first step in the evolution of complex multicellular organisms involves single cells forming a cooperative group. Consequently, to understand multicellularity, we need to understand the costs and benefits associated with multicellular group formation. We found that in the facultatively multicellular algae Chlorella sorokiniana: (1) the presence of the flagellate Ochromonas danica or the crustacean Daphnia magna leads to the formation of multicellular groups; (2) the formation of multicellular groups reduces predation by O. danica, but not by the larger predator D. magna; (3) under conditions of relatively low light intensity, where competition for light is greater, multicellular groups grow slower than single cells; (4) in the absence of live predators, the proportion of cells in multicellular groups decreases at a rate that does not vary with light intensity. These results can explain why, in cases such as this algae species, multicellular group formation is facultative, in response to the presence of predators.}, } @article {pmid30875767, year = {2019}, author = {Goh, GH and Maloney, SK and Mark, PJ and Blache, D}, title = {Episodic Ultradian Events-Ultradian Rhythms.}, journal = {Biology}, volume = {8}, number = {1}, pages = {}, pmid = {30875767}, issn = {2079-7737}, abstract = {In the fast lane of chronobiology, ultradian events are short-term rhythms that have been observed since the beginning of modern biology and were quantified about a century ago. They are ubiquitous in all biological systems and found in all organisms, from unicellular organisms to mammals, and from single cells to complex biological functions in multicellular animals. Since these events are aperiodic and last for a few minutes to a few hours, they are better classified as episodic ultradian events (EUEs). Their origin is unclear. However, they could have a molecular basis and could be controlled by hormonal inputs-in vertebrates, they originate from the activity of the central nervous system. EUEs are receiving increasing attention but their aperiodic nature requires specific sampling and analytic tools. While longer scale rhythms are adaptations to predictable changes in the environment, in theory, EUEs could contribute to adaptation by preparing organisms and biological functions for unpredictability.}, } @article {pmid30863851, year = {2019}, author = {Shoemark, DK and Ziegler, B and Watanabe, H and Strompen, J and Tucker, RP and Özbek, S and Adams, JC}, title = {Emergence of a Thrombospondin Superfamily at the Origin of Metazoans.}, journal = {Molecular biology and evolution}, volume = {36}, number = {6}, pages = {1220-1238}, pmid = {30863851}, issn = {1537-1719}, support = {MR/K018043/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Anthozoa/genetics/metabolism ; *Biological Evolution ; Hydra/physiology ; Invertebrates/*genetics ; Multigene Family ; Thrombospondins/*genetics/metabolism ; }, abstract = {Extracellular matrix (ECM) is considered central to the evolution of metazoan multicellularity; however, the repertoire of ECM proteins in nonbilaterians remains unclear. Thrombospondins (TSPs) are known to be well conserved from cnidarians to vertebrates, yet to date have been considered a unique family, principally studied for matricellular functions in vertebrates. Through searches utilizing the highly conserved C-terminal region of TSPs, we identify undisclosed new families of TSP-related proteins in metazoans, designated mega-TSP, sushi-TSP, and poriferan-TSP, each with a distinctive phylogenetic distribution. These proteins share the TSP C-terminal region domain architecture, as determined by domain composition and analysis of molecular models against known structures. Mega-TSPs, the only form identified in ctenophores, are typically >2,700 aa and are also characterized by N-terminal leucine-rich repeats and central cadherin/immunoglobulin domains. In cnidarians, which have a well-defined ECM, Mega-TSP was expressed throughout embryogenesis in Nematostella vectensis, with dynamic endodermal expression in larvae and primary polyps and widespread ectodermal expression in adult Nematostella vectensis and Hydra magnipapillata polyps. Hydra Mega-TSP was also expressed during regeneration and siRNA-silencing of Mega-TSP in Hydra caused specific blockade of head regeneration. Molecular phylogenetic analyses based on the conserved TSP C-terminal region identified each of the TSP-related groups to form clades distinct from the canonical TSPs. We discuss models for the evolution of the newly defined TSP superfamily by gene duplications, radiation, and gene losses from a debut in the last metazoan common ancestor. Together, the data provide new insight into the evolution of ECM and tissue organization in metazoans.}, } @article {pmid30862622, year = {2019}, author = {Lenhart, BA and Meeks, B and Murphy, HA}, title = {Variation in Filamentous Growth and Response to Quorum-Sensing Compounds in Environmental Isolates of Saccharomyces cerevisiae.}, journal = {G3 (Bethesda, Md.)}, volume = {9}, number = {5}, pages = {1533-1544}, pmid = {30862622}, issn = {2160-1836}, support = {R15 GM122032/GM/NIGMS NIH HHS/United States ; }, mesh = {*Environmental Microbiology ; *Gene-Environment Interaction ; *Genetic Variation ; Genome, Fungal ; Genomics/methods ; Hyphae ; Polymorphism, Single Nucleotide ; *Quorum Sensing/drug effects ; Saccharomyces cerevisiae/drug effects/isolation & purification/*physiology ; }, abstract = {In fungi, filamentous growth is a major developmental transition that occurs in response to environmental cues. In diploid Saccharomyces cerevisiae, it is known as pseudohyphal growth and presumed to be a foraging mechanism. Rather than unicellular growth, multicellular filaments composed of elongated, attached cells spread over and into surfaces. This morphogenetic switch can be induced through quorum sensing with the aromatic alcohols phenylethanol and tryptophol. Most research investigating pseudohyphal growth has been conducted in a single lab background, Σ1278b. To investigate the natural variation in this phenotype and its induction, we assayed the diverse 100-genomes collection of environmental isolates. Using computational image analysis, we quantified the production of pseudohyphae and observed a large amount of variation. Population origin was significantly associated with pseudohyphal growth, with the West African population having the most. Surprisingly, most strains showed little or no response to exogenous phenylethanol or tryptophol. We also investigated the amount of natural genetic variation in pseudohyphal growth using a mapping population derived from a highly-heterozygous clinical isolate that contained as much phenotypic variation as the environmental panel. A bulk-segregant analysis uncovered five major peaks with candidate loci that have been implicated in the Σ1278b background. Our results indicate that the filamentous growth response is a generalized, highly variable phenotype in natural populations, while response to quorum sensing molecules is surprisingly rare. These findings highlight the importance of coupling studies in tractable lab strains with natural isolates in order to understand the relevance and distribution of well-studied traits.}, } @article {pmid30860988, year = {2019}, author = {Riahi, H and Brekelmans, C and Foriel, S and Merkling, SH and Lyons, TA and Itskov, PM and Kleefstra, T and Ribeiro, C and van Rij, RP and Kramer, JM and Schenck, A}, title = {The histone methyltransferase G9a regulates tolerance to oxidative stress-induced energy consumption.}, journal = {PLoS biology}, volume = {17}, number = {3}, pages = {e2006146}, pmid = {30860988}, issn = {1545-7885}, mesh = {Animals ; Antioxidants/metabolism ; Energy Metabolism/genetics/physiology ; Epigenesis, Genetic/genetics ; Glycogen Phosphorylase/genetics/metabolism ; Histone Methyltransferases/genetics/*metabolism ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Humans ; Male ; Oxidative Stress/genetics/physiology ; Phylogeny ; Sequence Analysis, RNA ; }, abstract = {Stress responses are crucial processes that require activation of genetic programs that protect from the stressor. Stress responses are also energy consuming and can thus be deleterious to the organism. The mechanisms coordinating energy consumption during stress response in multicellular organisms are not well understood. Here, we show that loss of the epigenetic regulator G9a in Drosophila causes a shift in the transcriptional and metabolic responses to oxidative stress (OS) that leads to decreased survival time upon feeding the xenobiotic paraquat. During OS exposure, G9a mutants show overactivation of stress response genes, rapid depletion of glycogen, and inability to access lipid energy stores. The OS survival deficiency of G9a mutants can be rescued by a high-sugar diet. Control flies also show improved OS survival when fed a high-sugar diet, suggesting that energy availability is generally a limiting factor for OS tolerance. Directly limiting access to glycogen stores by knocking down glycogen phosphorylase recapitulates the OS-induced survival defects of G9a mutants. We propose that G9a mutants are sensitive to stress because they experience a net reduction in available energy due to (1) rapid glycogen use, (2) an inability to access lipid energy stores, and (3) an overinduced transcriptional response to stress that further exacerbates energy demands. This suggests that G9a acts as a critical regulatory hub between the transcriptional and metabolic responses to OS. Our findings, together with recent studies that established a role for G9a in hypoxia resistance in cancer cell lines, suggest that G9a is of wide importance in controlling the cellular and organismal response to multiple types of stress.}, } @article {pmid30857590, year = {2019}, author = {Sicard, A and Pirolles, E and Gallet, R and Vernerey, MS and Yvon, M and Urbino, C and Peterschmitt, M and Gutierrez, S and Michalakis, Y and Blanc, S}, title = {A multicellular way of life for a multipartite virus.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {30857590}, issn = {2050-084X}, support = {ANR-14-CE02-0014//Agence Nationale de la Recherche/International ; }, mesh = {DNA Viruses ; DNA, Viral/*genetics ; *Genome, Viral ; In Situ Hybridization, Fluorescence ; Microscopy, Confocal ; Nanovirus/*genetics/physiology ; Plant Diseases/*virology ; Regression Analysis ; Vicia faba/*virology ; Virion/*genetics ; Virus Replication ; }, abstract = {A founding paradigm in virology is that the spatial unit of the viral replication cycle is an individual cell. Multipartite viruses have a segmented genome where each segment is encapsidated separately. In this situation the viral genome is not recapitulated in a single virus particle but in the viral population. How multipartite viruses manage to efficiently infect individual cells with all segments, thus with the whole genome information, is a long-standing but perhaps deceptive mystery. By localizing and quantifying the genome segments of a nanovirus in host plant tissues we show that they rarely co-occur within individual cells. We further demonstrate that distinct segments accumulate independently in different cells and that the viral system is functional through complementation across cells. Our observation deviates from the classical conceptual framework in virology and opens an alternative possibility (at least for nanoviruses) where the infection can operate at a level above the individual cell level, defining a viral multicellular way of life.}, } @article {pmid30851154, year = {2019}, author = {Kalsoom, N and Zafar, M and Ahmad, M and Sultana, S and Usma, A and Jabeen, A}, title = {Investigating Schizocarp morphology as a taxonomic tool in study of Apiaceae family by utilizing LM and SEM techniques.}, journal = {Microscopy research and technique}, volume = {82}, number = {7}, pages = {1012-1020}, doi = {10.1002/jemt.23248}, pmid = {30851154}, issn = {1097-0029}, mesh = {Apiaceae/*anatomy & histology/*classification ; Fruit/*anatomy & histology/ultrastructure ; *Microscopy ; *Microscopy, Electron, Scanning ; Phylogeny ; Pollen ; }, abstract = {In present study, the schizocarp morphology of 14 species belonging to Apiaceae family has been investigated. Light microscopy (LM) and scanning electron microscopy (SEM) have been utilized to highlight qualitative and quantitative features of studied species. Variations have been observed in macro- and micro-morphological features such as color, shape, symmetry, length, width, apex, epicuticular projections, surface patterns, anticlinal, and periclinal wall patterns. Schizocarp shapes observed were oval, round, triangular, linear, elliptic, and globose. Fruit was either homomorphic or heteromorphic. Crystalloids, stellate hair, multicellular spines, and platelets were mostly observed epicuticular projections. Surface patterns on the fruit surface were striate, rugulate-striate, reticulate, and striato-knotted. Both macro- and micro-morphological characters can serve as an important tool in classifying Apiaceae family at various taxonomic ranks. Substantial variations observed can assist as useful constraints at various taxonomic levels as they provide reliable and constant details. Disparities observed in schizocarp features can pave a path for Apiaceae family classification based on phylogenetic and molecular studies.}, } @article {pmid30848356, year = {2019}, author = {Bondarenko, N and Bondarenko, A and Starunov, V and Slyusarev, G}, title = {Comparative analysis of the mitochondrial genomes of Orthonectida: insights into the evolution of an invertebrate parasite species.}, journal = {Molecular genetics and genomics : MGG}, volume = {294}, number = {3}, pages = {715-727}, pmid = {30848356}, issn = {1617-4623}, support = {19-04-0021//Russian Foundation for Basic Research/ ; 17-74-10103//Russian Science Foundation/ ; 1.40.496.2017//Saint Petersburg State University/ ; }, mesh = {Animals ; Base Composition/genetics ; DNA, Mitochondrial/chemistry/genetics ; *Evolution, Molecular ; Gastropoda/parasitology ; *Gene Order ; Genes, Mitochondrial/*genetics ; Genome, Mitochondrial/*genetics ; Helminths/parasitology ; Host-Parasite Interactions ; Invertebrates/classification/*genetics/physiology ; Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Among invertebrates, only a few groups still have uncertain phylogenetic position, Orthonectida, a small group of rare multi-cellular parasites of marine invertebrates, being one of them. Recent molecular and morphological findings suggest that orthonectids belong to Lophotrochozoa and are close to Annelida. Nevertheless, phylogenetic relationships between orthonectids and annelids are unclear, and the phylogeny within the group itself has never been studied. Sequencing of mitochondrial genomes is used here to clarify this issue. Complete mt genomes of the orthonectids Intoshia variabili and Rhopalura litoralis were characterized and compared with Intoshia linei mt genome. Our results show that Orthonectida mt genomes have undergone reduction and gene loss, and that they have complicated organization revealed in strand asymmetry in nucleotide composition, in some features of intergenic non-coding regions, tRNA duplication and folding. Moreover, all species of Orthonectida have a unique gene order with complicated rearrangement landscape. Significant differences in mitochondrial genomes in the three orthonectid species could be explained by the fact that their host species belong to different taxa (flat worms, nemertines and gastropods). Among the analyzed mt genomes of Orthonectida, I. linei possesses the closest gene order to the ancestral genome. All Orthonectida species are monophyletic, and in the phylogenetic tree are close to Pleistoannelida, and specifically, to Clitellata.}, } @article {pmid30846531, year = {2019}, author = {Sequeira-Mendes, J and Vergara, Z and Peiró, R and Morata, J and Aragüez, I and Costas, C and Mendez-Giraldez, R and Casacuberta, JM and Bastolla, U and Gutierrez, C}, title = {Differences in firing efficiency, chromatin, and transcription underlie the developmental plasticity of the Arabidopsis DNA replication origins.}, journal = {Genome research}, volume = {29}, number = {5}, pages = {784-797}, pmid = {30846531}, issn = {1549-5469}, mesh = {Arabidopsis/*genetics/growth & development ; Base Composition/genetics ; Cells, Cultured ; Chromatin/metabolism ; *DNA Replication ; Heterochromatin/*genetics ; Replication Origin/*genetics ; Retroelements/genetics ; Transcription Initiation Site ; Transcription, Genetic ; }, abstract = {Eukaryotic genome replication depends on thousands of DNA replication origins (ORIs). A major challenge is to learn ORI biology in multicellular organisms in the context of growing organs to understand their developmental plasticity. We have identified a set of ORIs of Arabidopsis thaliana and their chromatin landscape at two stages of post-embryonic development. ORIs associate with multiple chromatin signatures including transcription start sites (TSS) but also proximal and distal regulatory regions and heterochromatin, where ORIs colocalize with retrotransposons. In addition, quantitative analysis of ORI activity led us to conclude that strong ORIs have high GC content and clusters of GGN trinucleotides. Development primarily influences ORI firing strength rather than ORI location. ORIs that preferentially fire at early developmental stages colocalize with GC-rich heterochromatin, but at later stages with transcribed genes, perhaps as a consequence of changes in chromatin features associated with developmental processes. Our study provides the set of ORIs active in an organism at the post-embryo stage that should allow us to study ORI biology in response to development, environment, and mutations with a quantitative approach. In a wider scope, the computational strategies developed here can be transferred to other eukaryotic systems.}, } @article {pmid30839008, year = {2019}, author = {Ruiz, MC and Kljun, J and Turel, I and Di Virgilio, AL and León, IE}, title = {Comparative antitumor studies of organoruthenium complexes with 8-hydroxyquinolines on 2D and 3D cell models of bone, lung and breast cancer.}, journal = {Metallomics : integrated biometal science}, volume = {11}, number = {3}, pages = {666-675}, doi = {10.1039/c8mt00369f}, pmid = {30839008}, issn = {1756-591X}, mesh = {Antineoplastic Agents/chemistry/*pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cisplatin/chemistry/pharmacology ; Humans ; Models, Biological ; Neoplasms/*metabolism ; Organometallic Compounds/chemistry/*pharmacology ; Oxyquinoline/chemistry/*pharmacology ; Ruthenium/pharmacology ; Ruthenium Compounds/chemistry/*pharmacology ; }, abstract = {The purpose of this work was to screen the antitumor actions of two metal organoruthenium-8-hydroxyquinolinato (Ru-hq) complexes to find a potential novel agent for bone, lung and breast chemotherapies. We showed that ruthenium compounds (1 and 2) impaired the cell viability of human bone (MG-63), lung (A549) and breast (MCF7) cancer cells with greater selectivity and specificity than cisplatin. Besides, complexes 1 and 2 decreased proliferation, migration and invasion on cell monolayers at lower concentrations (2.5-10 μM). In addition, both compounds induced genotoxicity revealed by the micronucleus test, which led to G2/M cell cycle arrest and induced the tumor cells to undergo apoptosis. On the other hand, in multicellular 3D models (multicellular spheroids; MCS), 1 and 2 overcame CDDP presenting lower IC50 values only in MCS of lung origin. Moreover, 1 outperformed 2 in MCS of bone and breast origin. Finally, our findings revealed that both compounds inhibited the cell invasion of multicellular spheroids, showing that complex 1 exhibited the most important antimetastatic action. Taken together, these results indicate that compound 1 is an interesting candidate to be tested on in vivo models as a novel strategy for anticancer therapy.}, } @article {pmid30826447, year = {2019}, author = {Fillinger, RJ and Anderson, MZ}, title = {Seasons of change: Mechanisms of genome evolution in human fungal pathogens.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {70}, number = {}, pages = {165-174}, doi = {10.1016/j.meegid.2019.02.031}, pmid = {30826447}, issn = {1567-7257}, mesh = {Evolution, Molecular ; Fungi/*genetics/*pathogenicity ; Genome, Fungal/*genetics ; Genomics ; Humans ; Mycoses/etiology/*genetics ; }, abstract = {Fungi are a diverse kingdom of organisms capable of thriving in various niches across the world including those in close association with multicellular eukaryotes. Fungal pathogens that contribute to human disease reside both within the host as commensal organisms of the microbiota and the environment. Their niche of origin dictates how infection initiates but also places specific selective pressures on the fungal pathogen that contributes to its genome organization and genetic repertoire. Recent efforts to catalogue genomic variation among major human fungal pathogens have unveiled evolutionary themes that shape the fungal genome. Mechanisms ranging from large scale changes such as aneuploidy and ploidy cycling as well as more targeted mutations like base substitutions and gene copy number variations contribute to the evolution of these species, which are often under multiple competing selective pressures with their host, environment, and other microbes. Here, we provide an overview of the major selective pressures and mechanisms acting to evolve the genome of clinically important fungal pathogens of humans.}, } @article {pmid30824779, year = {2019}, author = {Kabir, M and Wenlock, S and Doig, AJ and Hentges, KE}, title = {The Essentiality Status of Mouse Duplicate Gene Pairs Correlates with Developmental Co-Expression Patterns.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {3224}, pmid = {30824779}, issn = {2045-2322}, support = {BB/L018276/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Algorithms ; Animals ; Animals, Newborn ; Embryonic Development/*genetics ; Evolution, Molecular ; *Gene Duplication ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Developmental ; Genes, Duplicate/*genetics ; Genes, Essential/*genetics ; Humans ; Mice ; Models, Genetic ; Organogenesis/genetics ; }, abstract = {During the evolution of multicellular eukaryotes, gene duplication occurs frequently to generate new genes and/or functions. A duplicated gene may have a similar function to its ancestral gene. Therefore, it may be expected that duplicated genes are less likely to be critical for the survival of an organism, since there are multiple copies of the gene rendering each individual copy redundant. In this study, we explored the developmental expression patterns of duplicate gene pairs and the relationship between development co-expression and phenotypes resulting from the knockout of duplicate genes in the mouse. We define genes that generate lethal phenotypes in single gene knockout experiments as essential genes. We found that duplicate gene pairs comprised of two essential genes tend to be expressed at different stages of development, compared to duplicate gene pairs with at least one non-essential member, showing that the timing of developmental expression affects the ability of one paralogue to compensate for the loss of the other. Gene essentiality, developmental expression and gene duplication are thus closely linked.}, } @article {pmid30824706, year = {2019}, author = {Lurgi, M and Thomas, T and Wemheuer, B and Webster, NS and Montoya, JM}, title = {Modularity and predicted functions of the global sponge-microbiome network.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {992}, pmid = {30824706}, issn = {2041-1723}, mesh = {Animals ; Bacteria/classification/genetics ; Biodiversity ; Biological Evolution ; Ecology ; Host Microbial Interactions/*physiology ; Microbiota/genetics/*physiology ; Phylogeny ; Porifera/classification/*microbiology ; RNA, Ribosomal, 16S/genetics ; Species Specificity ; Symbiosis ; }, abstract = {Defining the organisation of species interaction networks and unveiling the processes behind their assembly is fundamental to understanding patterns of biodiversity, community stability and ecosystem functioning. Marine sponges host complex communities of microorganisms that contribute to their health and survival, yet the mechanisms behind microbiome assembly are largely unknown. We present the global marine sponge-microbiome network and reveal a modular organisation in both community structure and function. Modules are linked by a few sponge species that share microbes with other species around the world. Further, we provide evidence that abiotic factors influence the structuring of the sponge microbiome when considering all microbes present, but biotic interactions drive the assembly of more intimately associated 'core' microorganisms. These findings suggest that both ecological and evolutionary processes are at play in host-microbe network assembly. We expect mechanisms behind microbiome assembly to be consistent across multicellular hosts throughout the tree of life.}, } @article {pmid30810962, year = {2019}, author = {Bai, SN}, title = {Plant Morphogenesis 123: a renaissance in modern botany?.}, journal = {Science China. Life sciences}, volume = {62}, number = {4}, pages = {453-466}, doi = {10.1007/s11427-018-9457-1}, pmid = {30810962}, issn = {1869-1889}, mesh = {Biological Evolution ; Botany/*trends ; Life Cycle Stages ; Meristem/cytology/growth & development ; Models, Biological ; Morphogenesis ; *Plant Development ; Plant Structures/growth & development ; Reproduction ; }, abstract = {Plants are a group of multicellular organisms crucial for the biosphere on the Earth. In the 17th century, the founding fathers of modern botany viewed the bud as the basic unit undergoing the plant life cycle. However, for many understandable reasons, the dominant conceptual framework evolved away from the "bud-centered" viewpoint to a "plant-centered" viewpoint that treated the whole plant, consisting of numerous buds, as a unit and considered the entire plant to be the functional equivalent of an animal individual. While this "plant-centered" viewpoint is convenient and great progress has been made using this conceptual framework, some fundamental problems remain logically unsolvable. Previously, I have proposed a new conceptual framework for interpretation of plant morphogenesis, called Plant Morphogenesis 123, which revives a "bud-centered" viewpoint. The perspective of Plant Morphogenesis 123 allows us to address new questions regarding to the mechanisms of plant morphogenesis that are important, and technically accessible, but previously neglected under the "plant-centered" conceptual framework. In addition to describing these questions, I address a more fundamental question for further discussion: why do people study plants?}, } @article {pmid30808737, year = {2019}, author = {El Albani, A and Mangano, MG and Buatois, LA and Bengtson, S and Riboulleau, A and Bekker, A and Konhauser, K and Lyons, T and Rollion-Bard, C and Bankole, O and Lekele Baghekema, SG and Meunier, A and Trentesaux, A and Mazurier, A and Aubineau, J and Laforest, C and Fontaine, C and Recourt, P and Chi Fru, E and Macchiarelli, R and Reynaud, JY and Gauthier-Lafaye, F and Canfield, DE}, title = {Organism motility in an oxygenated shallow-marine environment 2.1 billion years ago.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {9}, pages = {3431-3436}, pmid = {30808737}, issn = {1091-6490}, mesh = {Atmosphere ; *Biological Evolution ; Biota/physiology ; *Fossils ; Gabon ; Geologic Sediments/*chemistry ; Oxidation-Reduction ; Oxygen/*chemistry ; }, abstract = {Evidence for macroscopic life in the Paleoproterozoic Era comes from 1.8 billion-year-old (Ga) compression fossils [Han TM, Runnegar B (1992) Science 257:232-235; Knoll et al. (2006) Philos Trans R Soc Lond B 361:1023-1038], Stirling biota [Bengtson S et al. (2007) Paleobiology 33:351-381], and large colonial organisms exhibiting signs of coordinated growth from the 2.1-Ga Francevillian series, Gabon. Here we report on pyritized string-shaped structures from the Francevillian Basin. Combined microscopic, microtomographic, geochemical, and sedimentologic analyses provide evidence for biogenicity, and syngenicity and suggest that the structures underwent fossilization during early diagenesis close to the sediment-water interface. The string-shaped structures are up to 6 mm across and extend up to 170 mm through the strata. Morphological and 3D tomographic reconstructions suggest that the producer may have been a multicellular or syncytial organism able to migrate laterally and vertically to reach food resources. A possible modern analog is the aggregation of amoeboid cells into a migratory slug phase in cellular slime molds at times of starvation. This unique ecologic window established in an oxygenated, shallow-marine environment represents an exceptional record of the biosphere following the crucial changes that occurred in the atmosphere and ocean in the aftermath of the great oxidation event (GOE).}, } @article {pmid30803482, year = {2019}, author = {Trigos, AS and Pearson, RB and Papenfuss, AT and Goode, DL}, title = {Somatic mutations in early metazoan genes disrupt regulatory links between unicellular and multicellular genes in cancer.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {30803482}, issn = {2050-084X}, mesh = {Carcinogenesis ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; *Cell Transformation, Neoplastic ; Gene Dosage ; *Gene Regulatory Networks ; *Genes, Regulator ; Humans ; Neoplasms/*pathology ; *Point Mutation ; Transcription, Genetic ; }, abstract = {Extensive transcriptional alterations are observed in cancer, many of which activate core biological processes established in unicellular organisms or suppress differentiation pathways formed in metazoans. Through rigorous, integrative analysis of genomics data from a range of solid tumors, we show many transcriptional changes in tumors are tied to mutations disrupting regulatory interactions between unicellular and multicellular genes within human gene regulatory networks (GRNs). Recurrent point mutations were enriched in regulator genes linking unicellular and multicellular subnetworks, while copy-number alterations affected downstream target genes in distinctly unicellular and multicellular regions of the GRN. Our results depict drivers of tumourigenesis as genes that created key regulatory links during the evolution of early multicellular life, whose dysfunction creates widespread dysregulation of primitive elements of the GRN. Several genes we identified as important in this process were associated with drug response, demonstrating the potential clinical value of our approach.}, } @article {pmid30799483, year = {2019}, author = {Xie, P and Gao, M and Wang, C and Zhang, J and Noel, P and Yang, C and Von Hoff, D and Han, H and Zhang, MQ and Lin, W}, title = {SuperCT: a supervised-learning framework for enhanced characterization of single-cell transcriptomic profiles.}, journal = {Nucleic acids research}, volume = {47}, number = {8}, pages = {e48}, pmid = {30799483}, issn = {1362-4962}, support = {R01 MH109665/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Cell Lineage/genetics ; Cluster Analysis ; Datasets as Topic ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; High-Throughput Nucleotide Sequencing ; Humans ; Mice ; Pancreatic Neoplasms/*genetics ; RNA, Small Cytoplasmic/genetics ; Sequence Analysis, RNA ; Single-Cell Analysis/*statistics & numerical data ; *Software ; *Supervised Machine Learning ; *Transcriptome ; }, abstract = {Characterization of individual cell types is fundamental to the study of multicellular samples. Single-cell RNAseq techniques, which allow high-throughput expression profiling of individual cells, have significantly advanced our ability of this task. Currently, most of the scRNA-seq data analyses are commenced with unsupervised clustering. Clusters are often assigned to different cell types based on the enriched canonical markers. However, this process is inefficient and arbitrary. In this study, we present a technical framework of training the expandable supervised-classifier in order to reveal the single-cell identities as soon as the single-cell expression profile is input. Using multiple scRNA-seq datasets we demonstrate the superior accuracy, robustness, compatibility and expandability of this new solution compared to the traditional methods. We use two examples of the model upgrade to demonstrate how the projected evolution of the cell-type classifier is realized.}, } @article {pmid30796309, year = {2019}, author = {Zhang, L and Tan, Y and Fan, S and Zhang, X and Zhang, Z}, title = {Phylostratigraphic analysis of gene co-expression network reveals the evolution of functional modules for ovarian cancer.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {2623}, pmid = {30796309}, issn = {2045-2322}, support = {31800185//National Natural Science Foundation of China (National Science Foundation of China)/International ; 31800185//National Natural Science Foundation of China (National Science Foundation of China)/International ; }, mesh = {Biomarkers, Tumor/genetics ; Databases, Genetic ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Genome, Human ; Humans ; Ovarian Neoplasms/*genetics ; *Phylogeny ; }, abstract = {Ovarian cancer (OV) is an extremely lethal disease. However, the evolutionary machineries of OV are still largely unknown. Here, we used a method that combines phylostratigraphy information with gene co-expression networks to extensively study the evolutionary compositions of OV. The present co-expression network construction yielded 18,549 nodes and 114,985 edges based on 307 OV expression samples obtained from the Genome Data Analysis Centers database. A total of 20 modules were identified as OV related clusters. The human genome sequences were divided into 19 phylostrata (PS), the majority (67.45%) of OV genes was already present in the eukaryotic ancestor. There were two strong peaks of the emergence of OV genes screened by hypergeometric test: the evolution of the multicellular metazoan organisms (PS5 and PS6, P value = 0.002) and the emergence of bony fish (PS11 and PS12, P value = 0.009). Hence, the origin of OV is far earlier than its emergence. The integrated analysis of the topology of OV modules and the phylogenetic data revealed an evolutionary pattern of OV in human, namely, OV modules have arisen step by step during the evolution of the respective lineages. New genes have evolved and become locked into a pathway, where more and more biological pathways are fixed into OV modules by recruiting new genes during human evolution.}, } @article {pmid30794780, year = {2019}, author = {Tucci, V and Isles, AR and Kelsey, G and Ferguson-Smith, AC and , }, title = {Genomic Imprinting and Physiological Processes in Mammals.}, journal = {Cell}, volume = {176}, number = {5}, pages = {952-965}, doi = {10.1016/j.cell.2019.01.043}, pmid = {30794780}, issn = {1097-4172}, support = {210757/Z/18/Z//Wellcome Trust/United Kingdom ; 210757/Z/18/WT_/Wellcome Trust/United Kingdom ; MR/L010305/1/MRC_/Medical Research Council/United Kingdom ; MR/K011332/1/MRC_/Medical Research Council/United Kingdom ; BB/P002307/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/S000437/1/MRC_/Medical Research Council/United Kingdom ; BBS/E/B/000C0426/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/R009791/1/MRC_/Medical Research Council/United Kingdom ; BB/P008623/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Alleles ; Animals ; Biological Evolution ; Chromosomes ; DNA Methylation ; Epigenesis, Genetic/genetics/physiology ; Genomic Imprinting/*genetics/*physiology ; Mammals/*genetics/metabolism ; Physiological Phenomena ; }, abstract = {Complex multicellular organisms, such as mammals, express two complete sets of chromosomes per nucleus, combining the genetic material of both parents. However, epigenetic studies have demonstrated violations to this rule that are necessary for mammalian physiology; the most notable parental allele expression phenomenon is genomic imprinting. With the identification of endogenous imprinted genes, genomic imprinting became well-established as an epigenetic mechanism in which the expression pattern of a parental allele influences phenotypic expression. The expanding study of genomic imprinting is revealing a significant impact on brain functions and associated diseases. Here, we review key milestones in the field of imprinting and discuss mechanisms and systems in which imprinted genes exert a significant role.}, } @article {pmid30787483, year = {2019}, author = {Herron, MD and Borin, JM and Boswell, JC and Walker, J and Chen, IK and Knox, CA and Boyd, M and Rosenzweig, F and Ratcliff, WC}, title = {De novo origins of multicellularity in response to predation.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {2328}, pmid = {30787483}, issn = {2045-2322}, mesh = {Animals ; Cell Count ; Chlamydomonas reinhardtii/*cytology/ultrastructure ; Predatory Behavior/*physiology ; Rotifera/physiology ; }, abstract = {The transition from unicellular to multicellular life was one of a few major events in the history of life that created new opportunities for more complex biological systems to evolve. Predation is hypothesized as one selective pressure that may have driven the evolution of multicellularity. Here we show that de novo origins of simple multicellularity can evolve in response to predation. We subjected outcrossed populations of the unicellular green alga Chlamydomonas reinhardtii to selection by the filter-feeding predator Paramecium tetraurelia. Two of five experimental populations evolved multicellular structures not observed in unselected control populations within ~750 asexual generations. Considerable variation exists in the evolved multicellular life cycles, with both cell number and propagule size varying among isolates. Survival assays show that evolved multicellular traits provide effective protection against predation. These results support the hypothesis that selection imposed by predators may have played a role in some origins of multicellularity.}, } @article {pmid30787193, year = {2019}, author = {Dunning, LT and Olofsson, JK and Parisod, C and Choudhury, RR and Moreno-Villena, JJ and Yang, Y and Dionora, J and Quick, WP and Park, M and Bennetzen, JL and Besnard, G and Nosil, P and Osborne, CP and Christin, PA}, title = {Lateral transfers of large DNA fragments spread functional genes among grasses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {10}, pages = {4416-4425}, pmid = {30787193}, issn = {1091-6490}, support = {638333/ERC_/European Research Council/International ; MR/K001744/1/MRC_/Medical Research Council/United Kingdom ; BB/J004243/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Chromosomes, Plant ; DNA, Plant/*genetics ; *Gene Transfer, Horizontal ; *Genes, Plant ; Phylogeny ; Poaceae/classification/*genetics ; }, abstract = {A fundamental tenet of multicellular eukaryotic evolution is that vertical inheritance is paramount, with natural selection acting on genetic variants transferred from parents to offspring. This lineal process means that an organism's adaptive potential can be restricted by its evolutionary history, the amount of standing genetic variation, and its mutation rate. Lateral gene transfer (LGT) theoretically provides a mechanism to bypass many of these limitations, but the evolutionary importance and frequency of this process in multicellular eukaryotes, such as plants, remains debated. We address this issue by assembling a chromosome-level genome for the grass Alloteropsis semialata, a species surmised to exhibit two LGTs, and screen it for other grass-to-grass LGTs using genomic data from 146 other grass species. Through stringent phylogenomic analyses, we discovered 57 additional LGTs in the A. semialata nuclear genome, involving at least nine different donor species. The LGTs are clustered in 23 laterally acquired genomic fragments that are up to 170 kb long and have accumulated during the diversification of Alloteropsis. The majority of the 59 LGTs in A. semialata are expressed, and we show that they have added functions to the recipient genome. Functional LGTs were further detected in the genomes of five other grass species, demonstrating that this process is likely widespread in this globally important group of plants. LGT therefore appears to represent a potent evolutionary force capable of spreading functional genes among distantly related grass species.}, } @article {pmid30775966, year = {2019}, author = {Nakahara, N and Nobu, MK and Takaki, Y and Miyazaki, M and Tasumi, E and Sakai, S and Ogawara, M and Yoshida, N and Tamaki, H and Yamanaka, Y and Katayama, A and Yamaguchi, T and Takai, K and Imachi, H}, title = {Aggregatilinea lenta gen. nov., sp. nov., a slow-growing, facultatively anaerobic bacterium isolated from subseafloor sediment, and proposal of the new order Aggregatilineales ord. nov. within the class Anaerolineae of the phylum Chloroflexi.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {4}, pages = {1185-1194}, doi = {10.1099/ijsem.0.003291}, pmid = {30775966}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Bioreactors/*microbiology ; Chloroflexi/*classification/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Japan ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; }, abstract = {A novel slow-growing, facultatively anaerobic, filamentous bacterium, strain MO-CFX2[T], was isolated from a methanogenic microbial community in a continuous-flow bioreactor that was established from subseafloor sediment collected off the Shimokita Peninsula of Japan. Cells were multicellular filamentous, non-motile and Gram-stain-negative. The filaments were generally more than 20 µm (up to approximately 200 µm) long and 0.5-0.6 µm wide. Cells possessed pili-like structures on the cell surface and a multilayer structure in the cytoplasm. Growth of the strain was observed at 20-37 °C (optimum, 30 °C), pH 5.5-8.0 (pH 6.5-7.0), and 0-30 g l[-1] NaCl (5 g l[-1] NaCl). Under optimum growth conditions, doubling time and maximum cell density were estimated to be approximately 19 days and ~10[5] cells ml[-1], respectively. Strain MO-CFX2[T] grew chemoorganotrophically on a limited range of organic substrates in anaerobic conditions. The major cellular fatty acids were saturated C16 : 0 (47.9 %) and C18 : 0 (36.9 %), and unsaturated C18 : 1ω9c (6.0 %) and C16 : 1ω7 (5.1 %). The G+C content of genomic DNA was 63.2 mol%. 16S rRNA gene-based phylogenetic analysis showed that strain MO-CFX2[T] shares a notably low sequence identity with its closest relatives, which were Thermanaerothrix daxensis GNS-1[T] and Thermomarinilinea lacunifontana SW7[T] (both 85.8 % sequence identity). Based on these phenotypic and genomic properties, we propose the name Aggregatilinea lenta gen. nov., sp. nov. for strain MO-CFX2[T] (=KCTC 15625[T], =JCM 32065[T]). In addition, we also propose the associated family and order as Aggregatilineaceae fam. nov. and Aggregatilineales ord. nov., respectively.}, } @article {pmid30764885, year = {2019}, author = {Lipinska, AP and Serrano-Serrano, ML and Cormier, A and Peters, AF and Kogame, K and Cock, JM and Coelho, SM}, title = {Rapid turnover of life-cycle-related genes in the brown algae.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {35}, pmid = {30764885}, issn = {1474-760X}, support = {638240//European Research Council/International ; }, mesh = {*Evolution, Molecular ; Gene Duplication ; *Gene Expression ; Germ Cells, Plant ; Life Cycle Stages/*genetics ; Phaeophyta/*genetics/growth & development/metabolism ; Phenotype ; *Selection, Genetic ; }, abstract = {BACKGROUND: Sexual life cycles in eukaryotes involve a cyclic alternation between haploid and diploid phases. While most animals possess a diploid life cycle, many plants and algae alternate between multicellular haploid (gametophyte) and diploid (sporophyte) generations. In many algae, gametophytes and sporophytes are independent and free-living and may present dramatic phenotypic differences. The same shared genome can therefore be subject to different, even conflicting, selection pressures during each of the life cycle generations. Here, we analyze the nature and extent of genome-wide, generation-biased gene expression in four species of brown algae with contrasting levels of dimorphism between life cycle generations.

RESULTS: We show that the proportion of the transcriptome that is generation-specific is broadly associated with the level of phenotypic dimorphism between the life cycle stages. Importantly, our data reveals a remarkably high turnover rate for life-cycle-related gene sets across the brown algae and highlights the importance not only of co-option of regulatory programs from one generation to the other but also of a role for newly emerged, lineage-specific gene expression patterns in the evolution of the gametophyte and sporophyte developmental programs in this major eukaryotic group. Moreover, we show that generation-biased genes display distinct evolutionary modes, with gametophyte-biased genes evolving rapidly at the coding sequence level whereas sporophyte-biased genes tend to exhibit changes in their patterns of expression.

CONCLUSION: Our analysis uncovers the characteristics, expression patterns, and evolution of generation-biased genes and underlines the selective forces that shape this previously underappreciated source of phenotypic diversity.}, } @article {pmid30763317, year = {2019}, author = {Raza, Q and Choi, JY and Li, Y and O'Dowd, RM and Watkins, SC and Chikina, M and Hong, Y and Clark, NL and Kwiatkowski, AV}, title = {Evolutionary rate covariation analysis of E-cadherin identifies Raskol as a regulator of cell adhesion and actin dynamics in Drosophila.}, journal = {PLoS genetics}, volume = {15}, number = {2}, pages = {e1007720}, pmid = {30763317}, issn = {1553-7404}, support = {R01 GM121534/GM/NIGMS NIH HHS/United States ; R01 HG009299/HG/NHGRI NIH HHS/United States ; R01 HL127711/HL/NHLBI NIH HHS/United States ; R01 GM086423/GM/NIGMS NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/metabolism ; Actins/*metabolism ; Adherens Junctions/metabolism ; Animals ; Cadherins/*metabolism ; Cell Adhesion/*physiology ; Cell Membrane/metabolism ; Cell Movement/physiology ; Circadian Rhythm Signaling Peptides and Proteins/*metabolism ; Drosophila/*metabolism ; Drosophila Proteins/*metabolism ; Signal Transduction/physiology ; }, abstract = {The adherens junction couples the actin cytoskeletons of neighboring cells to provide the foundation for multicellular organization. The core of the adherens junction is the cadherin-catenin complex that arose early in the evolution of multicellularity to link actin to intercellular adhesions. Over time, evolutionary pressures have shaped the signaling and mechanical functions of the adherens junction to meet specific developmental and physiological demands. Evolutionary rate covariation (ERC) identifies proteins with correlated fluctuations in evolutionary rate that can reflect shared selective pressures and functions. Here we use ERC to identify proteins with evolutionary histories similar to the Drosophila E-cadherin (DE-cad) ortholog. Core adherens junction components α-catenin and p120-catenin displayed positive ERC correlations with DE-cad, indicating that they evolved under similar selective pressures during evolution between Drosophila species. Further analysis of the DE-cad ERC profile revealed a collection of proteins not previously associated with DE-cad function or cadherin-mediated adhesion. We then analyzed the function of a subset of ERC-identified candidates by RNAi during border cell (BC) migration and identified novel genes that function to regulate DE-cad. Among these, we found that the gene CG42684, which encodes a putative GTPase activating protein (GAP), regulates BC migration and adhesion. We named CG42684 raskol ("to split" in Russian) and show that it regulates DE-cad levels and actin protrusions in BCs. We propose that Raskol functions with DE-cad to restrict Ras/Rho signaling and help guide BC migration. Our results demonstrate that a coordinated selective pressure has shaped the adherens junction and this can be leveraged to identify novel components of the complexes and signaling pathways that regulate cadherin-mediated adhesion.}, } @article {pmid30762281, year = {2019}, author = {Chen, IK and Satinsky, BM and Velicer, GJ and Yu, YN}, title = {sRNA-pathway genes regulating myxobacterial development exhibit clade-specific evolution.}, journal = {Evolution & development}, volume = {21}, number = {2}, pages = {82-95}, doi = {10.1111/ede.12281}, pmid = {30762281}, issn = {1525-142X}, support = {GM079690/NH/NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; Genome, Bacterial ; Mutagenesis, Insertional ; Myxococcus xanthus/*genetics/growth & development ; Phenotype ; Phylogeny ; RNA, Small Untranslated/*genetics ; }, abstract = {Small non-coding RNAs (sRNAs) control bacterial gene expression involved in a wide range of important cellular processes. In the highly social bacterium Myxococcus xanthus, the sRNA Pxr prevents multicellular fruiting-body development when nutrients are abundant. Pxr was discovered from the evolution of a developmentally defective strain (OC) into a developmentally proficient strain (PX). In OC, Pxr is constitutively expressed and blocks development even during starvation. In PX, one mutation deactivates Pxr allowing development to proceed. We screened for transposon mutants that suppress the OC defect and thus potentially reveal new Pxr-pathway components. Insertions significantly restoring development were found in four genes-rnd, rnhA, stkA and Mxan_5793-not previously associated with an sRNA activity. Phylogenetic analysis suggests that the Pxr pathway was constructed within the Cystobacterineae suborder both by co-option of genes predating the Myxococcales order and incorporation of a novel gene (Mxan_5793). Further, the sequence similarity of rnd, rnhA and stkA homologs relative to M. xanthus alleles was found to decrease greatly among species beyond the Cystobacterineae suborder compared to the housekeeping genes examined. Finally, ecological context differentially affected the developmental phenotypes of distinct mutants, with implications for the evolution of development in variable environments.}, } @article {pmid30761165, year = {2019}, author = {Dipp-Álvarez, M and Cruz-Ramírez, A}, title = {A Phylogenetic Study of the ANT Family Points to a preANT Gene as the Ancestor of Basal and euANT Transcription Factors in Land Plants.}, journal = {Frontiers in plant science}, volume = {10}, number = {}, pages = {17}, pmid = {30761165}, issn = {1664-462X}, abstract = {Comparative genomics has revealed that members of early divergent lineages of land plants share a set of highly conserved transcription factors (TFs) with flowering plants. While gene copy numbers have expanded through time, it has been predicted that diversification, co-option, and reassembly of gene regulatory networks implicated in development are directly related to morphological innovations that led to more complex land plant bodies. Examples of key networks have been deeply studied in Arabidopsis thaliana, such as those involving the AINTEGUMENTA (ANT) gene family that encodes AP2-type TFs. These TFs play significant roles in plant development such as the maintenance of stem cell niches, the correct development of the embryo and the formation of lateral organs, as well as fatty acid metabolism. Previously, it has been hypothesized that the common ancestor of mosses and vascular plants encoded two ANT genes that later diversified in seed plants. However, algae and bryophyte sequences have been underrepresented from such phylogenetic analyses. To understand the evolution of ANT in a complete manner, we performed phylogenetic analyses of ANT protein sequences of representative species from across the Streptophyta clade, including algae, liverworts, and hornworts, previously unrepresented. Moreover, protein domain architecture, selection analyses, and regulatory cis elements prediction, allowed us to propose a scenario of how the evolution of ANT genes occurred. In this study we show that a duplication of a preANT-like gene in the ancestor of embryophytes may have given rise to the land plant-exclusive basalANT and euANT lineages. We hypothesize that the absence of euANT-type and basalANT-type sequences in algae, and its presence in extant land plant species, suggests that the divergence of pre-ANT into basal and eu-ANT clades in embryophytes may have influenced the conquest of land by plants, as ANT TFs play important roles in tolerance to desiccation and the establishment, maintenance, and development of complex multicellular structures which either became more complex or appeared in land plants.}, } @article {pmid30760850, year = {2019}, author = {Junqueira Alves, C and Yotoko, K and Zou, H and Friedel, RH}, title = {Origin and evolution of plexins, semaphorins, and Met receptor tyrosine kinases.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {1970}, pmid = {30760850}, issn = {2045-2322}, support = {R01 NS092735/NS/NINDS NIH HHS/United States ; }, mesh = {Amino Acid Sequence/genetics ; Animals ; Biological Evolution ; Cell Adhesion Molecules/*genetics ; Choanoflagellata/*genetics ; Databases, Genetic ; Echinodermata/*genetics ; Humans ; Nerve Tissue Proteins/*genetics ; Protein Domains/genetics ; Proto-Oncogene Proteins c-met/*genetics ; Receptors, Cell Surface/genetics ; Semaphorins/*genetics ; }, abstract = {The transition from unicellular to multicellular organisms poses the question as to when genes that regulate cell-cell interactions emerged during evolution. The receptor and ligand pairing of plexins and semaphorins regulates cellular interactions in a wide range of developmental and physiological contexts. We surveyed here genomes of unicellular eukaryotes and of non-bilaterian and bilaterian Metazoa and performed phylogenetic analyses to gain insight into the evolution of plexin and semaphorin families. Remarkably, we detected plexins and semaphorins in unicellular choanoflagellates, indicating their evolutionary origin in a common ancestor of Choanoflagellida and Metazoa. The plexin domain structure is conserved throughout all clades; in contrast, semaphorins are structurally diverse. Choanoflagellate semaphorins are transmembrane proteins with multiple fibronectin type III domains following the N-terminal Sema domain (termed Sema-FN). Other previously not yet described semaphorin classes include semaphorins of Ctenophora with tandem immunoglobulin domains (Sema-IG) and secreted semaphorins of Echinoderamata (Sema-SP, Sema-SI). Our study also identified Met receptor tyrosine kinases (RTKs), which carry a truncated plexin extracellular domain, in several bilaterian clades, indicating evolutionary origin in a common ancestor of Bilateria. In addition, a novel type of Met-like RTK with a complete plexin extracellular domain was detected in Lophotrochozoa and Echinodermata (termed Met-LP RTK). Our findings are consistent with an ancient function of plexins and semaphorins in regulating cytoskeletal dynamics and cell adhesion that predates their role as axon guidance molecules.}, } @article {pmid30760717, year = {2019}, author = {Ferrari, C and Proost, S and Janowski, M and Becker, J and Nikoloski, Z and Bhattacharya, D and Price, D and Tohge, T and Bar-Even, A and Fernie, A and Stitt, M and Mutwil, M}, title = {Kingdom-wide comparison reveals the evolution of diurnal gene expression in Archaeplastida.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {737}, pmid = {30760717}, issn = {2041-1723}, mesh = {Chlorophyta/genetics ; *Circadian Rhythm ; Embryophyta/genetics ; Eukaryota/classification/*genetics ; *Evolution, Molecular ; Gene Expression Profiling/*methods ; Photosynthesis/genetics ; Phylogeny ; Rhodophyta/genetics ; Transcriptome/*genetics ; }, abstract = {Plants have adapted to the diurnal light-dark cycle by establishing elaborate transcriptional programs that coordinate many metabolic, physiological, and developmental responses to the external environment. These transcriptional programs have been studied in only a few species, and their function and conservation across algae and plants is currently unknown. We performed a comparative transcriptome analysis of the diurnal cycle of nine members of Archaeplastida, and we observed that, despite large phylogenetic distances and dramatic differences in morphology and lifestyle, diurnal transcriptional programs of these organisms are similar. Expression of genes related to cell division and the majority of biological pathways depends on the time of day in unicellular algae but we did not observe such patterns at the tissue level in multicellular land plants. Hence, our study provides evidence for the universality of diurnal gene expression and elucidates its evolutionary history among different photosynthetic eukaryotes.}, } @article {pmid30740458, year = {2019}, author = {Oborník, M}, title = {In the beginning was the word: How terminology drives our understanding of endosymbiotic organelles.}, journal = {Microbial cell (Graz, Austria)}, volume = {6}, number = {2}, pages = {134-141}, pmid = {30740458}, issn = {2311-2638}, abstract = {The names we give objects of research, to some extent, predispose our ways of thinking about them. Misclassifications of Oomycota, Microsporidia, Myxosporidia, and Helicosporidia have obviously affected not only their formal taxonomic names, but also the methods and approaches with which they have been investigated. Therefore, it is important to name biological entities with accurate terms in order to avoid discrepancies in researching them. The endosymbiotic origin of mitochondria and plastids is now the most accepted scenario for their evolution. Since it is apparent that there is no natural definitive border between bacteria and semiautonomous organelles, I propose that mitochondria and plastids should be called bacteria and classified accordingly, in the bacterial classification system. I discuss some consequences of this approach, including: i) the resulting "changes" in the abundances of bacteria, ii) the definitions of terms like microbiome or multicellularity, and iii) the concept of endosymbiotic domestication.}, } @article {pmid30729842, year = {2019}, author = {Tan, J and He, Q and Pentz, JT and Peng, C and Yang, X and Tsai, MH and Chen, Y and Ratcliff, WC and Jiang, L}, title = {Copper oxide nanoparticles promote the evolution of multicellularity in yeast.}, journal = {Nanotoxicology}, volume = {13}, number = {5}, pages = {597-605}, doi = {10.1080/17435390.2018.1553253}, pmid = {30729842}, issn = {1743-5404}, mesh = {*Biological Evolution ; Copper/*toxicity ; Gene Expression Regulation, Fungal/drug effects ; Nanoparticles/*toxicity ; Saccharomyces cerevisiae/cytology/*drug effects/genetics ; Transcriptome/drug effects ; }, abstract = {Engineered nanomaterials are rapidly becoming an essential component of modern technology. Thousands of tons of nanomaterials are manufactured, used, and subsequently released into the environment annually. While the presence of these engineered nanomaterials in the environment has profound effects on various biological systems in the short term, little work has been done to understand their consequences over long, evolutionary timescales. The evolution of multicellularity is a critical step in the origin of complex life on Earth and a unique strategy for microorganisms to alleviate adverse environmental impacts, yet the selective pressures that favor the evolution of multicellular groups remain poorly understood. Here, we show that engineered nanomaterials, specifically copper oxide nanoparticles (CuO NPs), promote the evolution of undifferentiated multicellularity in Baker's yeast (Saccharomyces cerevisiae strain Y55). Transcriptomic analysis suggests that multicellularity mitigates the negative effects of CuO NPs in yeast cells and shifts their metabolism from alcoholic fermentation towards aerobic respiration, potentially increasing resource efficiency and providing a fitness benefit during CuO NP exposure. Competition assays also confirm that the multicellular yeast possesses a fitness advantage when exposed to CuO NPs. Our results, therefore, demonstrate that nanoparticles can have profound and unexpected evolutionary consequences, underscoring the need for a more comprehensive understanding of the long-term biological impacts of nanomaterial pollution.}, } @article {pmid30728304, year = {2019}, author = {Peyraud, R and Mbengue, M and Barbacci, A and Raffaele, S}, title = {Intercellular cooperation in a fungal plant pathogen facilitates host colonization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {8}, pages = {3193-3201}, pmid = {30728304}, issn = {1091-6490}, support = {336808/ERC_/European Research Council/International ; }, mesh = {Arabidopsis/genetics/growth & development/*microbiology ; Ascomycota/genetics/*pathogenicity ; Genome, Plant/genetics ; Host-Pathogen Interactions/*genetics ; Hyphae/genetics/pathogenicity ; Plant Diseases/*genetics/microbiology ; }, abstract = {Cooperation is associated with major transitions in evolution such as the emergence of multicellularity. It is central to the evolution of many complex traits in nature, including growth and virulence in pathogenic bacteria. Whether cells of multicellular parasites function cooperatively during infection remains, however, largely unknown. Here, we show that hyphal cells of the fungal pathogen Sclerotinia sclerotiorum reprogram toward division of labor to facilitate the colonization of host plants. Using global transcriptome sequencing, we reveal that gene expression patterns diverge markedly in cells at the center and apex of hyphae during Arabidopsis thaliana colonization compared with in vitro growth. We reconstructed a genome-scale metabolic model for S. sclerotiorum and used flux balance analysis to demonstrate metabolic heterogeneity supporting division of labor between hyphal cells. Accordingly, continuity between the central and apical compartments of invasive hyphae was required for optimal growth in planta Using a multicell model of fungal hyphae, we show that this cooperative functioning enhances fungal growth predominantly during host colonization. Our work identifies cooperation in fungal hyphae as a mechanism emerging at the multicellular level to support host colonization and virulence.}, } @article {pmid30720904, year = {2019}, author = {Xiong, F and Ren, JJ and Yu, Q and Wang, YY and Kong, LJ and Otegui, MS and Wang, XL}, title = {AtBUD13 affects pre-mRNA splicing and is essential for embryo development in Arabidopsis.}, journal = {The Plant journal : for cell and molecular biology}, volume = {98}, number = {4}, pages = {714-726}, doi = {10.1111/tpj.14268}, pmid = {30720904}, issn = {1365-313X}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/classification/genetics/*metabolism ; Embryonic Development/genetics/*physiology ; Gene Expression Regulation, Developmental/genetics ; Gene Expression Regulation, Plant/genetics ; Genes, Plant/genetics ; Introns ; Mutation ; Nuclear Proteins/classification/genetics/*metabolism ; Phylogeny ; Plants, Genetically Modified ; Protein Domains ; RNA Precursors/genetics ; RNA Splicing ; RNA Splicing Factors/classification/genetics/*metabolism ; Sequence Alignment ; Sequence Analysis ; }, abstract = {Pre-mRNA splicing is an important step for gene expression regulation. Yeast Bud13p (bud-site selection protein 13) regulates the budding pattern and pre-mRNA splicing in yeast cells; however, no Bud13p homologs have been identified in plants. Here, we isolated two mutants that carry T-DNA insertions at the At1g31870 locus and shows early embryo lethality and seed abortion. At1g31870 encodes an Arabidopsis homolog of yeast Bud13p, AtBUD13. Although AtBUD13 homologs are widely distributed in eukaryotic organisms, phylogenetic analysis revealed that their protein domain organization is more complex in multicellular species. AtBUD13 is expressed throughout plant development including embryogenesis and AtBUD13 proteins is localized in the nucleus in Arabidopsis. RNA-seq analysis revealed that AtBUD13 mutation predominantly results in the intron retention, especially for shorter introns (≤100 bases). Within this group of genes, we identified 52 genes involved in embryogenesis, out of which 22 are involved in nucleic acid metabolism. Our results demonstrate that AtBUD13 plays critical roles in early embryo development by effecting pre-mRNA splicing.}, } @article {pmid30718271, year = {2019}, author = {Fischer, MS and Jonkers, W and Glass, NL}, title = {Integration of Self and Non-self Recognition Modulates Asexual Cell-to-Cell Communication in Neurospora crassa.}, journal = {Genetics}, volume = {211}, number = {4}, pages = {1255-1267}, pmid = {30718271}, issn = {1943-2631}, support = {P01 GM068087/GM/NIGMS NIH HHS/United States ; S10 OD021828/OD/NIH HHS/United States ; T32 GM007127/GM/NIGMS NIH HHS/United States ; }, mesh = {*Chemotaxis ; Fungal Proteins/genetics/metabolism ; MAP Kinase Signaling System ; Neurospora crassa/genetics/*physiology ; *Quorum Sensing ; }, abstract = {Cells rarely exist alone, which drives the evolution of diverse mechanisms for identifying and responding appropriately to the presence of other nearby cells. Filamentous fungi depend on somatic cell-to-cell communication and fusion for the development and maintenance of a multicellular, interconnected colony that is characteristic of this group of organisms. The filamentous fungus Neurospora crassa is a model for investigating the mechanisms of somatic cell-to-cell communication and fusion. N. crassa cells chemotropically grow toward genetically similar cells, which ultimately make physical contact and undergo cell fusion. Here, we describe the development of a Pprm1-luciferase reporter system that differentiates whether genes function upstream or downstream of a conserved MAP kinase (MAPK) signaling complex, by using a set of mutants required for communication and cell fusion. The vast majority of these mutants are deficient for self-fusion and for fusion when paired with wild-type cells. However, the Δham-11 mutant is unique in that it fails to undergo self-fusion, but chemotropic interactions and cell fusion are restored in Δham-11 + wild-type interactions. In genetically dissimilar cells, chemotropic interactions are regulated by genetic differences at doc-1 and doc-2, which regulate prefusion non-self recognition; cells with dissimilar doc-1 and doc-2 alleles show greatly reduced cell-fusion frequencies. Here, we show that HAM-11 functions in parallel with the DOC-1 and DOC-2 proteins to regulate the activity of the MAPK signaling complex. Together, our data support a model of integrated self and non-self recognition processes that modulate somatic cell-to-cell communication in N. crassa.}, } @article {pmid30717103, year = {2019}, author = {Gonçalves, DS and Ferreira, MDS and Guimarães, AJ}, title = {Extracellular Vesicles from the Protozoa Acanthamoeba castellanii: Their Role in Pathogenesis, Environmental Adaptation and Potential Applications.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {6}, number = {1}, pages = {}, pmid = {30717103}, issn = {2306-5354}, support = {JCNE 2018//Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro - FAPERJ./ ; }, abstract = {Extracellular vesicles (EVs) are membranous compartments of distinct cellular origin and biogenesis, displaying different sizes and include exosomes, microvesicles, and apoptotic bodies. The EVs have been described in almost every living organism, from simple unicellular to higher evolutionary scale multicellular organisms, such as mammals. Several functions have been attributed to these structures, including roles in energy acquisition, cell-to-cell communication, gene expression modulation and pathogenesis. In this review, we described several aspects of the recently characterized EVs of the protozoa Acanthamoeba castellanii, a free-living amoeba (FLA) of emerging epidemiological importance, and compare their features to other parasites' EVs. These A. castellanii EVs are comprised of small microvesicles and exosomes and carry a wide range of molecules involved in many biological processes like cell signaling, carbohydrate metabolism and proteolytic activity, such as kinases, glucanases, and proteases, respectively. Several biomedical applications of these EVs have been proposed lately, including their use in vaccination, biofuel production, and the pharmaceutical industry, such as platforms for drug delivery.}, } @article {pmid30715320, year = {2019}, author = {Voukantsis, D and Kahn, K and Hadley, M and Wilson, R and Buffa, FM}, title = {Modeling genotypes in their microenvironment to predict single- and multi-cellular behavior.}, journal = {GigaScience}, volume = {8}, number = {3}, pages = {}, pmid = {30715320}, issn = {2047-217X}, support = {CBIG:23969//Cancer Research UK/United Kingdom ; }, mesh = {Cell Hypoxia ; Cell Lineage ; Cell Proliferation ; *Cellular Microenvironment ; Clonal Evolution ; Computer Simulation ; Gene Regulatory Networks ; Genotype ; Humans ; Mutation/genetics ; Signal Transduction ; Spheroids, Cellular/cytology ; }, abstract = {A cell's phenotype is the set of observable characteristics resulting from the interaction of the genotype with the surrounding environment, determining cell behavior. Deciphering genotype-phenotype relationships has been crucial to understanding normal and disease biology. Analysis of molecular pathways has provided an invaluable tool to such understanding; however, typically it does not consider the physical microenvironment, which is a key determinant of phenotype. In this study, we present a novel modeling framework that enables the study of the link between genotype, signaling networks, and cell behavior in a three-dimensional microenvironment. To achieve this, we bring together Agent-Based Modeling, a powerful computational modeling technique, and gene networks. This combination allows biological hypotheses to be tested in a controlled stepwise fashion, and it lends itself naturally to model a heterogeneous population of cells acting and evolving in a dynamic microenvironment, which is needed to predict the evolution of complex multi-cellular dynamics. Importantly, this enables modeling co-occurring intrinsic perturbations, such as mutations, and extrinsic perturbations, such as nutrient availability, and their interactions. Using cancer as a model system, we illustrate how this framework delivers a unique opportunity to identify determinants of single-cell behavior, while uncovering emerging properties of multi-cellular growth. This framework is freely available at http://www.microc.org.}, } @article {pmid30714631, year = {2019}, author = {Baluška, F and Reber, A}, title = {Sentience and Consciousness in Single Cells: How the First Minds Emerged in Unicellular Species.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {41}, number = {3}, pages = {e1800229}, doi = {10.1002/bies.201800229}, pmid = {30714631}, issn = {1521-1878}, mesh = {Animals ; Awareness/physiology ; Biological Evolution ; Cell Membrane/*physiology ; Consciousness/*physiology ; Cytoskeleton/*physiology ; Escherichia coli/physiology ; Humans ; Lipid Bilayers/chemistry ; Membrane Potential, Mitochondrial/physiology ; Plant Cells/physiology ; Polymers/chemistry ; Synaptic Potentials/physiology ; }, abstract = {A reductionistic, bottom-up, cellular-based concept of the origins of sentience and consciousness has been put forward. Because all life is based on cells, any evolutionary theory of the emergence of sentience and consciousness must be grounded in mechanisms that take place in prokaryotes, the simplest unicellular species. It has been posited that subjective awareness is a fundamental property of cellular life. It emerges as an inherent feature of, and contemporaneously with, the very first life-forms. All other varieties of mentation are the result of evolutionary mechanisms based on this singular event. Therefore, all forms of sentience and consciousness evolve from this original instantiation in prokaryotes. It has also been identified that three cellular structures and mechanisms that likely play critical roles here are excitable membranes, oscillating cytoskeletal polymers, and structurally flexible proteins. Finally, basic biophysical principles are proposed to guide those processes that underly the emergence of supracellular sentience from cellular sentience in multicellular organisms.}, } @article {pmid30705751, year = {2018}, author = {Kosach, V and Shkarina, K and Kravchenko, A and Tereshchenko, Y and Kovalchuk, E and Skoroda, L and Krotevych, M and Khoruzhenko, A}, title = {Nucleocytoplasmic distribution of S6K1 depends on the density and motility of MCF-7 cells in vitro.}, journal = {F1000Research}, volume = {7}, number = {}, pages = {1332}, pmid = {30705751}, issn = {2046-1402}, mesh = {*Breast Neoplasms ; Cell Movement ; Humans ; MCF-7 Cells ; Ribosomal Protein S6 Kinases, 70-kDa ; Signal Transduction ; }, abstract = {Background: The ribosomal protein S6 kinase 1 (S6K1) is one of the main components of the mTOR/S6K signal transduction pathway, which controls cellular metabolism, autophagy, growth, and proliferation. Overexpression of S6K1 was detected in tumors of different origin including breast cancer, and correlated with the worse disease outcome. In addition, significant accumulation of S6K1 was found in the nuclei of breast carcinoma cells suggesting the implication of kinase nuclear substrates in tumor progression. However, this aspect of S6K1 functioning is still poorly understood. The main aim of the present work was to study the subcellular localization of S6K1 in breast cancer cells with the focus on cell migration. Methods: Multicellular spheroids of MCF-7 cells were generated using agarose-coated Petri dishes. Cell migration was induced by spheroids seeding onto adhesive growth surface and subsequent cultivation for 24 to 72 hours. The subcellular localization of S6K1 was studied in human normal breast and cancer tissue samples, 2D and 3D MCF-7 cell cultures using immunofluorescence analysis and confocal microscopy. Results: Analysis of histological sections of human breast tissue samples revealed predominantly nuclear localization of S6K1 in breast malignant cells and its mainly cytoplasmic localization in conditionally normal cells. In vitro studies of MCF-7 cells demonstrated that the subcellular localization of S6K1 depends on the cell density in the monolayer culture. S6K1 relocalization from the cytoplasm into the nucleus was detected in MCF-7 cells migrating from multicellular spheroids onto growth surface. Immunofluorescence analysis of S6K1 and immunocoprecipitation assay revealed the colocalization and interaction between S6K1 and transcription factor TBR2 (T-box brain protein 2) in MCF-7 cells. Conclusions: Subcellular localization of S6K1 depends on the density and locomotor activity of the MCF-7 cells.}, } @article {pmid30699103, year = {2019}, author = {Helsen, J and Frickel, J and Jelier, R and Verstrepen, KJ}, title = {Network hubs affect evolvability.}, journal = {PLoS biology}, volume = {17}, number = {1}, pages = {e3000111}, pmid = {30699103}, issn = {1545-7885}, mesh = {*Gene Regulatory Networks ; }, abstract = {The regulatory processes in cells are typically organized into complex genetic networks. However, it is still unclear how this network structure modulates the evolution of cellular regulation. One would expect that mutations in central and highly connected modules of a network (so-called hubs) would often result in a breakdown and therefore be an evolutionary dead end. However, a new study by Koubkova-Yu and colleagues finds that in some circumstances, altering a hub can offer a quick evolutionary advantage. Specifically, changes in a hub can induce significant phenotypic changes that allow organisms to move away from a local fitness peak, whereas the fitness defects caused by the perturbed hub can be mitigated by mutations in its interaction partners. Together, the results demonstrate how network architecture shapes and facilitates evolutionary adaptation.}, } @article {pmid30698789, year = {2019}, author = {Muley, VY and Akhter, Y and Galande, S}, title = {PDZ Domains Across the Microbial World: Molecular Link to the Proteases, Stress Response, and Protein Synthesis.}, journal = {Genome biology and evolution}, volume = {11}, number = {3}, pages = {644-659}, pmid = {30698789}, issn = {1759-6653}, mesh = {*Biological Evolution ; Genes, Microbial ; *Genome, Bacterial ; *Genome, Fungal ; *Multigene Family ; Oxidoreductases/genetics ; *PDZ Domains ; Peptide Hydrolases/genetics ; Protein Biosynthesis ; Stress, Physiological ; }, abstract = {The PSD-95/Dlg-A/ZO-1 (PDZ) domain is highly expanded, diversified, and well distributed across metazoa where it assembles diverse signaling components by virtue of interactions with other proteins in a sequence-specific manner. In contrast, in the microbial world they are reported to be involved in protein quality control during stress response. The distribution, functions, and origins of PDZ domain-containing proteins in the prokaryotic organisms remain largely unexplored. We analyzed 7,852 PDZ domain-containing proteins in 1,474 microbial genomes in this context. PDZ domain-containing proteins from planctomycetes, myxobacteria, and other eubacteria occupying terrestrial and aquatic niches are found to be in multiple copies within their genomes. Over 93% of the 7,852 PDZ domain-containing proteins were classified into 12 families including six novel families based on additional structural and functional domains present in these proteins. The higher PDZ domain encoding capacity of the investigated organisms was observed to be associated with adaptation to the ecological niche where multicellular life might have originated and flourished. Predicted subcellular localization of PDZ domain-containing proteins and their genomic context argue in favor of crucial roles in translation and membrane remodeling during stress response. Based on rigorous sequence, structure, and phylogenetic analyses, we propose that the highly diverse PDZ domain of the uncharacterized Fe-S oxidoreductase superfamily, exclusively found in gladobacteria and several anaerobes and acetogens, might represent the most ancient form among all the existing PDZ domains.}, } @article {pmid30691027, year = {2019}, author = {Salmina, K and Huna, A and Kalejs, M and Pjanova, D and Scherthan, H and Cragg, MS and Erenpreisa, J}, title = {The Cancer Aneuploidy Paradox: In the Light of Evolution.}, journal = {Genes}, volume = {10}, number = {2}, pages = {}, pmid = {30691027}, issn = {2073-4425}, mesh = {*Aneuploidy ; *Evolution, Molecular ; Genomic Instability ; HeLa Cells ; Humans ; Kinetochores/metabolism ; Mitosis ; Neoplasms/*genetics ; Recombination, Genetic ; Spindle Apparatus/genetics/metabolism ; }, abstract = {Aneuploidy should compromise cellular proliferation but paradoxically favours tumour progression and poor prognosis. Here, we consider this paradox in terms of our most recent observations of chemo/radio-resistant cells undergoing reversible polyploidy. The latter perform the segregation of two parental groups of end-to-end linked dyads by pseudo-mitosis creating tetraploid cells through a dysfunctional spindle. This is followed by autokaryogamy and a homologous pairing preceding a bi-looped endo-prophase. The associated RAD51 and DMC1/γ-H2AX double-strand break repair foci are tandemly situated on the AURKB/REC8/kinetochore doublets along replicated chromosome loops, indicative of recombination events. MOS-associated REC8-positive peri-nucleolar centromere cluster organises a monopolar spindle. The process is completed by reduction divisions (bi-polar or by radial cytotomy including pedogamic exchanges) and by the release of secondary cells and/or the formation of an embryoid. Together this process preserves genomic integrity and chromosome pairing, while tolerating aneuploidy by by-passing the mitotic spindle checkpoint. Concurrently, it reduces the chromosome number and facilitates recombination that decreases the mutation load of aneuploidy and lethality in the chemo-resistant tumour cells. This cancer life-cycle has parallels both within the cycling polyploidy of the asexual life cycles of ancient unicellular protists and cleavage embryos of early multicellulars, supporting the atavistic theory of cancer.}, } @article {pmid30689829, year = {2019}, author = {Parey, E and Crombach, A}, title = {Evolution of the Drosophila melanogaster Chromatin Landscape and Its Associated Proteins.}, journal = {Genome biology and evolution}, volume = {11}, number = {3}, pages = {660-677}, pmid = {30689829}, issn = {1759-6653}, mesh = {Animals ; Chromatin/classification/*genetics ; DNA-Binding Proteins/genetics ; Drosophila Proteins/genetics ; Drosophila melanogaster/*genetics ; *Evolution, Molecular ; Histone Code ; }, abstract = {In the nucleus of eukaryotic cells, genomic DNA associates with numerous protein complexes and RNAs, forming the chromatin landscape. Through a genome-wide study of chromatin-associated proteins in Drosophila cells, five major chromatin types were identified as a refinement of the traditional binary division into hetero- and euchromatin. These five types were given color names in reference to the Greek word chroma. They are defined by distinct but overlapping combinations of proteins and differ in biological and biochemical properties, including transcriptional activity, replication timing, and histone modifications. In this work, we assess the evolutionary relationships of chromatin-associated proteins and present an integrated view of the evolution and conservation of the fruit fly Drosophila melanogaster chromatin landscape. We combine homology prediction across a wide range of species with gene age inference methods to determine the origin of each chromatin-associated protein. This provides insight into the evolution of the different chromatin types. Our results indicate that for the euchromatic types, YELLOW and RED, young associated proteins are more specialized than old ones; and for genes found in either chromatin type, intron/exon structure is lineage-specific. Next, we provide evidence that a subset of GREEN-associated proteins is involved in a centromere drive in D. melanogaster. Our results on BLUE chromatin support the hypothesis that the emergence of Polycomb Group proteins is linked to eukaryotic multicellularity. In light of these results, we discuss how the regulatory complexification of chromatin links to the origins of eukaryotic multicellularity.}, } @article {pmid30686614, year = {2019}, author = {Perner, J and Gasser, RB and Oliveira, PL and Kopáček, P}, title = {Haem Biology in Metazoan Parasites - 'The Bright Side of Haem'.}, journal = {Trends in parasitology}, volume = {35}, number = {3}, pages = {213-225}, doi = {10.1016/j.pt.2019.01.001}, pmid = {30686614}, issn = {1471-5007}, mesh = {Adaptation, Physiological ; Animals ; Heme/biosynthesis/genetics/*metabolism ; Host-Parasite Interactions/*physiology ; }, abstract = {Traditionally, host haem has been recognized as a cytotoxic molecule that parasites need to eliminate or detoxify in order to survive. However, recent evidence indicates that some lineages of parasites have lost genes that encode enzymes involved specifically in endogenous haem biosynthesis. Such lineages thus need to acquire and utilize haem originating from their host animal, making it an indispensable molecule for their survival and reproduction. In multicellular parasites, host haem needs to be systemically distributed throughout their bodies to meet the haem demands in all cell and tissue types. Host haem also gets deposited in parasite eggs, enabling embryogenesis and reproduction. Clearly, a better understanding of haem biology in multicellular parasites should elucidate organismal adaptations to obligatory blood-feeding.}, } @article {pmid30685797, year = {2019}, author = {Nedelcu, AM}, title = {Independent evolution of complex development in animals and plants: deep homology and lateral gene transfer.}, journal = {Development genes and evolution}, volume = {229}, number = {1}, pages = {25-34}, pmid = {30685797}, issn = {1432-041X}, mesh = {Animals ; Conserved Sequence ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; Plant Proteins/chemistry/genetics ; Plants/genetics ; Protein Domains ; *Sequence Homology ; Transcription Factors/chemistry/genetics ; }, abstract = {The evolution of multicellularity is a premier example of phenotypic convergence: simple multicellularity evolved independently many times, and complex multicellular phenotypes are found in several distant groups. Furthermore, both animal and plant lineages have independently reached extreme levels of morphological, functional, and developmental complexity. This study explores the genetic basis for the parallel evolution of complex multicellularity and development in the animal and green plant (i.e., green algae and land plants) lineages. Specifically, the study (i) identifies the SAND domain-a DNA-binding domain with important roles in the regulation of cell proliferation and differentiation, as unique to animals, green algae, and land plants; and (ii) suggests that the parallel deployment of this ancestral domain in similar regulatory roles could have contributed to the independent evolution of complex development in these distant groups. Given the deep animal-green plant divergence, the limited distribution of the SAND domain is best explained by invoking a lateral gene transfer (LGT) event from a green alga to an early metazoan. The presence of a sequence motif specifically shared by a family of SAND-containing transcription factors involved in the evolution of complex multicellularity in volvocine algae and two types of SAND proteins that emerged early in the evolution of animals is consistent with this scenario. Overall, these findings imply that (i) in addition to be involved in the evolution of similar phenotypes, deep homologous sequences can also contribute to shaping parallel evolutionary trajectories in distant lineages, and (ii) LGT could provide an additional source of latent homologous sequences that can be deployed in analogous roles and affect the evolutionary potentials of distantly related groups.}, } @article {pmid30668717, year = {2019}, author = {Belato, FA and Schrago, CG and Coates, CJ and Halanych, KM and Costa-Paiva, EM}, title = {Newly Discovered Occurrences and Gene Tree of the Extracellular Globins and Linker Chains from the Giant Hexagonal Bilayer Hemoglobin in Metazoans.}, journal = {Genome biology and evolution}, volume = {11}, number = {3}, pages = {597-612}, pmid = {30668717}, issn = {1759-6653}, mesh = {Animals ; Globins/*genetics ; Invertebrates/*genetics ; *Phylogeny ; }, abstract = {Multicellular organisms depend on oxygen-carrying proteins to transport oxygen throughout the body; therefore, proteins such as hemoglobins (Hbs), hemocyanins, and hemerythrins are essential for maintenance of tissues and cellular respiration. Vertebrate Hbs are among the most extensively studied proteins; however, much less is known about invertebrate Hbs. Recent studies of hemocyanins and hemerythrins have demonstrated that they have much wider distributions than previously thought, suggesting that oxygen-binding protein diversity is underestimated across metazoans. Hexagonal bilayer hemoglobin (HBL-Hb), a blood pigment found exclusively in annelids, is a polymer comprised up to 144 extracellular globins and 36 linker chains. To further understand the evolutionary history of this protein complex, we explored the diversity of linkers and extracellular globins from HBL-Hbs using in silico approaches on 319 metazoan and one choanoflagellate transcriptomes. We found 559 extracellular globin and 414 linker genes transcribed in 171 species from ten animal phyla with new records in Echinodermata, Hemichordata, Brachiopoda, Mollusca, Nemertea, Bryozoa, Phoronida, Platyhelminthes, and Priapulida. Contrary to previous suggestions that linkers and extracellular globins emerged in the annelid ancestor, our findings indicate that they have putatively emerged before the protostome-deuterostome split. For the first time, we unveiled the comprehensive evolutionary history of metazoan HBL-Hb components, which consists of multiple episodes of gene gains and losses. Moreover, because our study design surveyed linkers and extracellular globins independently, we were able to cross-validate our results, significantly reducing the rate of false positives. We confirmed that the distribution of HBL-Hb components has until now been underestimated among animals.}, } @article {pmid30668691, year = {2019}, author = {Passow, CN and Bronikowski, AM and Blackmon, H and Parsai, S and Schwartz, TS and McGaugh, SE}, title = {Contrasting Patterns of Rapid Molecular Evolution within the p53 Network across Mammal and Sauropsid Lineages.}, journal = {Genome biology and evolution}, volume = {11}, number = {3}, pages = {629-643}, pmid = {30668691}, issn = {1759-6653}, support = {R01 AG049416/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; *Genes, p53 ; Phylogeny ; *Selection, Genetic ; Vertebrates/*genetics ; }, abstract = {Cancer is a threat to multicellular organisms, yet the molecular evolution of pathways that prevent the accumulation of genetic damage has been largely unexplored. The p53 network regulates how cells respond to DNA-damaging stressors. We know little about p53 network molecular evolution as a whole. In this study, we performed comparative genetic analyses of the p53 network to quantify the number of genes within the network that are rapidly evolving and constrained, and the association between lifespan and the patterns of evolution. Based on our previous published data set, we used genomes and transcriptomes of 34 sauropsids and 32 mammals to analyze the molecular evolution of 45 genes within the p53 network. We found that genes in the network exhibited evidence of positive selection and divergent molecular evolution in mammals and sauropsids. Specifically, we found more evidence of positive selection in sauropsids than mammals, indicating that sauropsids have different targets of selection. In sauropsids, more genes upstream in the network exhibited positive selection, and this observation is driven by positive selection in squamates, which is consistent with previous work showing rapid divergence and adaptation of metabolic and stress pathways in this group. Finally, we identified a negative correlation between maximum lifespan and the number of genes with evidence of divergent molecular evolution, indicating that species with longer lifespans likely experienced less variation in selection across the network. In summary, our study offers evidence that comparative genomic approaches can provide insights into how molecular networks have evolved across diverse species.}, } @article {pmid30667071, year = {2019}, author = {Coelho, SM and Mignerot, L and Cock, JM}, title = {Origin and evolution of sex-determination systems in the brown algae.}, journal = {The New phytologist}, volume = {222}, number = {4}, pages = {1751-1756}, doi = {10.1111/nph.15694}, pmid = {30667071}, issn = {1469-8137}, support = {638240/ERC_/European Research Council/International ; }, mesh = {*Biological Evolution ; Gene Regulatory Networks ; Genetic Loci ; Phaeophyta/*genetics ; Sex Chromosomes ; }, abstract = {Sexual reproduction is a nearly universal feature of eukaryotic organisms. Meiosis appears to have had a single ancient origin, but the mechanisms underlying male or female sex determination are diverse and have emerged repeatedly and independently in the different eukaryotic groups. The brown algae are a group of multicellular photosynthetic eukaryotes that have a distinct evolutionary history compared with animals and plants, as they have been evolving independently for over 1 billion yr. Here, we review recent work using the brown alga Ectocarpus as a model organism to study haploid sex chromosomes, and highlight how the diversity of reproductive and life cycle features of the brown algae offer unique opportunities to characterize the evolutionary forces and the mechanisms underlying the evolution of sex determination.}, } @article {pmid30663729, year = {2019}, author = {Peel, S and Corrigan, AM and Ehrhardt, B and Jang, KJ and Caetano-Pinto, P and Boeckeler, M and Rubins, JE and Kodella, K and Petropolis, DB and Ronxhi, J and Kulkarni, G and Foster, AJ and Williams, D and Hamilton, GA and Ewart, L}, title = {Introducing an automated high content confocal imaging approach for Organs-on-Chips.}, journal = {Lab on a chip}, volume = {19}, number = {3}, pages = {410-421}, doi = {10.1039/c8lc00829a}, pmid = {30663729}, issn = {1473-0189}, mesh = {Animals ; Automation ; Drug Evaluation, Preclinical ; Humans ; Kidney/diagnostic imaging/drug effects ; *Lab-On-A-Chip Devices ; Liver/diagnostic imaging/drug effects ; Optical Imaging/*instrumentation ; Rats ; }, abstract = {Organ-Chips are micro-engineered systems that aim to recapitulate the organ microenvironment. Implementation of Organ-Chips within the pharmaceutical industry aims to improve the probability of success of drugs reaching late stage clinical trial by generating models for drug discovery that are of human origin and have disease relevance. We are adopting the use of Organ-Chips for enhancing pre-clinical efficacy and toxicity evaluation and prediction. Whilst capturing cellular phenotype via imaging in response to drug exposure is a useful readout in these models, application has been limited due to difficulties in imaging the chips at scale. Here we created an end-to-end, automated workflow to capture and analyse confocal images of multicellular Organ-Chips to assess detailed cellular phenotype across large batches of chips. By automating this process, we not only reduced acquisition time, but we also minimised process variability and user bias. This enabled us to establish, for the first time, a framework of statistical best practice for Organ-Chip imaging, creating the capability of using Organ-Chips and imaging for routine testing in drug discovery applications that rely on quantitative image data for decision making. We tested our approach using benzbromarone, whose mechanism of toxicity has been linked to mitochondrial damage with subsequent induction of apoptosis and necrosis, and staurosporine, a tool inducer of apoptosis. We also applied this workflow to assess the hepatotoxic effect of an active AstraZeneca drug candidate illustrating its applicability in drug safety assessment beyond testing tool compounds. Finally, we have demonstrated that this approach could be adapted to Organ-Chips of different shapes and sizes through application to a Kidney-Chip.}, } @article {pmid30662758, year = {2018}, author = {Bogdan, MJ and Savin, T}, title = {Fingering instabilities in tissue invasion: an active fluid model.}, journal = {Royal Society open science}, volume = {5}, number = {12}, pages = {181579}, pmid = {30662758}, issn = {2054-5703}, abstract = {Metastatic tumours often invade healthy neighbouring tissues by forming multicellular finger-like protrusions emerging from the cancer mass. To understand the mechanical context behind this phenomenon, we here develop a minimalist fluid model of a self-propelled, growing biological tissue. The theory involves only four mechanical parameters and remains analytically trackable in various settings. As an application of the model, we study the evolution of a two-dimensional circular droplet made of our active and expanding fluid, and embedded in a passive non-growing tissue. This system could be used to model the evolution of a carcinoma in an epithelial layer. We find that our description can explain the propensity of tumour tissues to fingering instabilities, as conditioned by the magnitude of active traction and the growth kinetics. We are also able to derive predictions for the tumour size at the onset of metastasis, and for the number of subsequent invasive fingers. Our active fluid model may help describe a wider range of biological processes, including wound healing and developmental patterning.}, } @article {pmid30659161, year = {2019}, author = {Rodríguez-Pascual, F}, title = {How evolution made the matrix punch at the multicellularity party.}, journal = {The Journal of biological chemistry}, volume = {294}, number = {3}, pages = {770-771}, pmid = {30659161}, issn = {1083-351X}, mesh = {Animals ; Basement Membrane/*metabolism ; *Evolution, Molecular ; Humans ; Protein Serine-Threonine Kinases/*genetics/*metabolism ; }, abstract = {The basement membrane is a specialized sheet-like form of the extracellular matrix that provides structural support to epithelial cells and tissues, while influencing multiple biological functions, and was essential in the transition to multicellularity. By exploring a variety of genomes, Darris et al. provide evidence that the emergence and divergence of a multifunctional Goodpasture antigen-binding protein (GPBP), a basement membrane constituent, played a role in this transition. These findings help to explain how GPBP contributed to the formation of these extracellular matrices and to more precisely define the transition to multicellular organisms.}, } @article {pmid30653459, year = {2019}, author = {Yoshida, T and Prudent, M and D'alessandro, A}, title = {Red blood cell storage lesion: causes and potential clinical consequences.}, journal = {Blood transfusion = Trasfusione del sangue}, volume = {17}, number = {1}, pages = {27-52}, pmid = {30653459}, issn = {2385-2070}, support = {R44 HL132172/HL/NHLBI NIH HHS/United States ; }, mesh = {*Blood Preservation ; Erythrocyte Transfusion/adverse effects/methods ; Erythrocytes/cytology/*metabolism ; Humans ; Oxygen/metabolism ; Pharmaceutical Solutions/pharmacology ; Time Factors ; }, abstract = {Red blood cells (RBCs) are a specialised organ that enabled the evolution of multicellular organisms by supplying a sufficient quantity of oxygen to cells that cannot obtain oxygen directly from ambient air via diffusion, thereby fueling oxidative phosphorylation for highly efficient energy production. RBCs have evolved to optimally serve this purpose by packing high concentrations of haemoglobin in their cytosol and shedding nuclei and other organelles. During their circulatory lifetimes in humans of approximately 120 days, RBCs are poised to transport oxygen by metabolic/redox enzymes until they accumulate damage and are promptly removed by the reticuloendothelial system. These elaborate evolutionary adaptions, however, are no longer effective when RBCs are removed from the circulation and stored hypothermically in blood banks, where they develop storage-induced damages ("storage lesions") that accumulate over the shelf life of stored RBCs. This review attempts to provide a comprehensive view of the literature on the subject of RBC storage lesions and their purported clinical consequences by incorporating the recent exponential growth in available data obtained from "omics" technologies in addition to that published in more traditional literature. To summarise this vast amount of information, the subject is organised in figures with four panels: i) root causes; ii) RBC storage lesions; iii) physiological effects; and iv) reported outcomes. The driving forces for the development of the storage lesions can be roughly classified into two root causes: i) metabolite accumulation/depletion, the target of various interventions (additive solutions) developed since the inception of blood banking; and ii) oxidative damages, which have been reported for decades but not addressed systemically until recently. Downstream physiological consequences of these storage lesions, derived mainly by in vitro studies, are described, and further potential links to clinical consequences are discussed. Interventions to postpone the onset and mitigate the extent of the storage lesion development are briefly reviewed. In addition, we briefly discuss the results from recent randomised controlled trials on the age of stored blood and clinical outcomes of transfusion.}, } @article {pmid30651122, year = {2019}, author = {Patthy, L}, title = {Exon skipping-rich transcriptomes of animals reflect the significance of exon-shuffling in metazoan proteome evolution.}, journal = {Biology direct}, volume = {14}, number = {1}, pages = {2}, pmid = {30651122}, issn = {1745-6150}, mesh = {Alternative Splicing ; Animals ; *Evolution, Molecular ; *Exons ; *Genome ; *Introns ; *Transcriptome ; }, abstract = {ᅟ: Animals are known to have higher rates of exon skipping than other eukaryotes. In a recent study, Grau-Bové et al. (Genome Biology 19:135, 2018) have used RNA-seq data across 65 eukaryotic species to investigate when and how this high prevalence of exon skipping evolved. They have found that bilaterian Metazoa have significantly increased exon skipping frequencies compared to all other eukaryotic groups and that exon skipping in nearly all animals, including non-bilaterians, is strongly enriched for frame-preserving events. The authors have hypothesized that "the increase of exon skipping rates in animals followed a two-step process. First, exon skipping in early animals became enriched for frame-preserving events. Second, bilaterian ancestors dramatically increased their exon skipping frequencies, likely driven by the interplay between a shift in their genome architectures towards more exon definition and recruitment of frame-preserving exon skipping events to functionally diversify their cell-specific proteomes." Here we offer a different explanation for the higher frequency of frame-preserving exon skipping in Metzoa than in all other eukaryotes. In our view these observations reflect the fact that the majority of multidomain proteins unique to metazoa and indispensable for metazoan type multicellularity were assembled by exon-shuffling from 'symmetrical' modules (i.e. modules flanked by introns of the same phase), whereas this type of protein evolution played a minor role in other groups of eukaryotes, including plants. The higher frequency of 'symmetrical' exons in Metazoan genomes provides an explanation for the enrichment for frame-preserving events since skipping or inclusion of 'symmetrical' modules during alternative splicing does not result in a reading-frame shift. REVIEWERS: This article was reviewed by Manuel Irimia, Ashish Lal and Erez Levanon. The reviewers were nominated by the Editorial Board.}, } @article {pmid30649338, year = {2019}, author = {Russell, SL}, title = {Transmission mode is associated with environment type and taxa across bacteria-eukaryote symbioses: a systematic review and meta-analysis.}, journal = {FEMS microbiology letters}, volume = {366}, number = {3}, pages = {}, doi = {10.1093/femsle/fnz013}, pmid = {30649338}, issn = {1574-6968}, mesh = {Bacteria/classification ; *Bacterial Physiological Phenomena ; *Biological Evolution ; *Environment ; Eukaryota/*physiology ; Host-Pathogen Interactions/*physiology ; Phylogeny ; Symbiosis/*physiology ; }, abstract = {Symbiotic associations between bacteria and eukaryotes exhibit a range of transmission strategies. The rates and distributions of transmission modes have not been thoroughly investigated across associations, despite their consequences on symbiont and host evolution. To address this empirically, I compiled data from the literature on bacteria-multicellular eukaryote associations for which transmission mode data was available. Of the total 528 analyzed symbioses, 21.2% were strictly horizontally transmitted, 36.0% exhibited some form of mixed mode transmission and 42.8% were strictly vertically transmitted. Controlling for phylogenetically independent symbiosis events revealed modes were approximately equally distributed among the 113 independent associations, at 32.1%+/-0.57% horizontal, 37.8%+/-1.4% mixed mode and 31.1%+/-1.3% vertical transmission. Binning symbioses by environment revealed an abundance of vertical transmission on land and a lack of it in aquatic environments. The naturally occurring uneven distribution of taxa among environments prevented controlling for host/symbiont phylogeny. However, the results were robust over a large number of independently evolved associations, suggesting that many vertically transmitted bacteria are capable of mixed mode transmission and barriers exist that reduce the rate of horizontal transmission events. Thus, both the environment type and host/symbiont taxa influence symbiont transmission mode evolution.}, } @article {pmid30644818, year = {2019}, author = {Arun, A and Coelho, SM and Peters, AF and Bourdareau, S and Pérès, L and Scornet, D and Strittmatter, M and Lipinska, AP and Yao, H and Godfroy, O and Montecinos, GJ and Avia, K and Macaisne, N and Troadec, C and Bendahmane, A and Cock, JM}, title = {Convergent recruitment of TALE homeodomain life cycle regulators to direct sporophyte development in land plants and brown algae.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {30644818}, issn = {2050-084X}, support = {ERC-SEXYPARTH/ERC_/European Research Council/International ; ANR-10-BLAN-1727//Agence Nationale de la Recherche/International ; Marinexus//Interreg Program France -England/International ; European Erasmus Mundus program//European Commission/International ; Marinexus//Interreg Program France (Channel)-England/International ; ANR-10-LABX-40//Agence Nationale de la Recherche/International ; 638240/ERC_/European Research Council/International ; ANR-10-BTBR-04-01//Agence Nationale de la Recherche/International ; }, mesh = {Amino Acid Sequence ; Embryophyta/genetics/*growth & development/*metabolism ; Evolution, Molecular ; Gene Expression Regulation, Plant ; Homeodomain Proteins/chemistry/genetics/*metabolism ; Mutation/genetics ; Phaeophyta/genetics/*growth & development/*metabolism ; Phenotype ; Plant Proteins/*metabolism ; Protein Binding ; Protein Domains ; RNA, Messenger/genetics/metabolism ; Transcription Factors/chemistry/genetics ; }, abstract = {Three amino acid loop extension homeodomain transcription factors (TALE HD TFs) act as life cycle regulators in green algae and land plants. In mosses these regulators are required for the deployment of the sporophyte developmental program. We demonstrate that mutations in either of two TALE HD TF genes, OUROBOROS or SAMSARA, in the brown alga Ectocarpus result in conversion of the sporophyte generation into a gametophyte. The OUROBOROS and SAMSARA proteins heterodimerise in a similar manner to TALE HD TF life cycle regulators in the green lineage. These observations demonstrate that TALE-HD-TF-based life cycle regulation systems have an extremely ancient origin, and that these systems have been independently recruited to regulate sporophyte developmental programs in at least two different complex multicellular eukaryotic supergroups, Archaeplastida and Chromalveolata.}, } @article {pmid30633881, year = {2019}, author = {Khalil, AA and de Rooij, J}, title = {Cadherin mechanotransduction in leader-follower cell specification during collective migration.}, journal = {Experimental cell research}, volume = {376}, number = {1}, pages = {86-91}, doi = {10.1016/j.yexcr.2019.01.006}, pmid = {30633881}, issn = {1090-2422}, mesh = {Actomyosin/genetics ; Animals ; Cadherins/chemistry/*genetics ; Cell Movement/*genetics ; Cell Polarity/*genetics ; Humans ; Intercellular Junctions/genetics ; Mechanotransduction, Cellular/*genetics ; Microtubules/genetics ; }, abstract = {Collective invasion drives the spread of multicellular cancer groups, into the normal tissue surrounding several epithelial tumors. Collective invasion recapitulates various aspects of the multicellular organization and collective migration that take place during normal development and repair. Collective migration starts with the specification of leader cells in which a polarized, migratory phenotype is established. Leader cells initiate and organize the migration of follower cells, to allow the group of cells to move as a cohesive and polarized unit. Leader-follower specification is essential for coordinated and directional collective movement. Forces exerted by cohesive cells represent key signals that dictate multicellular coordination and directionality. Physical forces originate from the contraction of the actomyosin cytoskeleton, which is linked between cells via cadherin-based cell-cell junctions. The cadherin complex senses and transduces fluctuations in forces into biochemical signals that regulate processes like cell proliferation, motility and polarity. With cadherin junctions being maintained in most collective movements the cadherin complex is ideally positioned to integrate mechanical information into the organization of collective cell migration. Here we discuss the potential roles of cadherin mechanotransduction in the diverse aspects of leader versus follower cell specification during collective migration and neoplastic invasion.}, } @article {pmid30633408, year = {2019}, author = {Škaloud, P and Škaloudová, M and Doskočilová, P and Kim, JI and Shin, W and Dvořák, P}, title = {Speciation in protists: Spatial and ecological divergence processes cause rapid species diversification in a freshwater chrysophyte.}, journal = {Molecular ecology}, volume = {28}, number = {5}, pages = {1084-1095}, doi = {10.1111/mec.15011}, pmid = {30633408}, issn = {1365-294X}, support = {17-13254S//Czech Science Foundation/International ; NRF-2015R1A2A2A01003192//National Research Foundation of Korea/International ; }, mesh = {Biodiversity ; *Biological Evolution ; Chrysophyta/*genetics/growth & development ; DNA, Mitochondrial/genetics ; *Ecosystem ; Fresh Water ; *Genetic Speciation ; Haplotypes/genetics ; Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Although eukaryotic microorganisms are extremely numerous, diverse and essential to global ecosystem functioning, they are largely understudied by evolutionary biologists compared to multicellular macroscopic organisms. In particular, very little is known about the speciation mechanisms which may give rise to the diversity of microscopic eukaryotes. It was postulated that the enormous population sizes and ubiquitous distribution of these organisms could lead to a lack of population differentiation and therefore very low speciation rates. However, such assumptions have traditionally been based on morphospecies, which may not accurately reflect the true diversity, missing cryptic taxa. In this study, we aim to articulate the major diversification mechanisms leading to the contemporary molecular diversity by using a colonial freshwater flagellate, Synura sphagnicola, as an example. Phylogenetic analysis of five sequenced loci showed that S. sphagnicola differentiated into two morphologically distinct lineages approximately 15.4 million years ago, which further diverged into several evolutionarily recent haplotypes during the late Pleistocene. The most recent haplotypes are ecologically and biogeographically much more differentiated than the old lineages, presumably because of their persistent differentiation after the allopatric speciation events. Our study shows that in microbial eukaryotes, species diversification via the colonization of new geographical regions or ecological resources occurs much more readily than was previously thought. Consequently, divergence times of microorganisms in some lineages may be equivalent to the estimated times of speciation in plants and animals.}, } @article {pmid30626024, year = {2019}, author = {Oxford, JT and Reeck, JC and Hardy, MJ}, title = {Extracellular Matrix in Development and Disease.}, journal = {International journal of molecular sciences}, volume = {20}, number = {1}, pages = {}, pmid = {30626024}, issn = {1422-0067}, support = {P20 GM103408/GM/NIGMS NIH HHS/United States ; P20 GM109095/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Disease ; Extracellular Matrix/*metabolism ; *Growth and Development ; Humans ; Integrins/metabolism ; Muscles/metabolism ; Reproduction ; Tissue Engineering ; }, abstract = {The evolution of multicellular metazoan organisms was marked by the inclusion of an extracellular matrix (ECM), a multicomponent, proteinaceous network between cells that contributes to the spatial arrangement of cells and the resulting tissue organization. [...].}, } @article {pmid30622924, year = {2018}, author = {Piché, A}, title = {Malignant peritoneal effusion acting as a tumor environment in ovarian cancer progression: Impact and significance.}, journal = {World journal of clinical oncology}, volume = {9}, number = {8}, pages = {167-171}, pmid = {30622924}, issn = {2218-4333}, abstract = {Until recently, ovarian cancer research has mainly focused on the tumor cells themselves ignoring for the most part the surrounding tumor environment which includes malignant peritoneal effusions. However, one of the major conceptual advances in oncology over the last few years has been the appreciation that cancer progression cannot be explained by aberrations in cancer cells themselves and is strongly influenced by the surrounding tumor environment. The mechanisms of ovarian cancer progression differ from that of other solid tumors because ovarian cancer cells primarily disseminate within the peritoneal cavity. Malignant peritoneal effusion accumulates in the peritoneal cavity during ovarian cancer progression. These exudative fluids act as a unique tumor environment providing a framework that orchestrates cellular and molecular changes contributing to aggressiveness and disease progression. The composition of ascites, which includes cellular and acellular components, constantly adapts during the course of the disease in response to various cellular cues originating from both tumor and stromal cells. The tumor environment that represents peritoneal effusions closely constitute an ecosystem, with specific cell types and signaling molecules increasing and decreasing during the course of the disease progression creating a single complex network. Although recent advances aiming to understand the ovarian tumor environment have focused one at a time on components, the net impact of the whole environment cannot be understood simply from its parts or outside is environmental context.}, } @article {pmid30622525, year = {2018}, author = {Li, XG and Zhang, WJ and Xiao, X and Jian, HH and Jiang, T and Tang, HZ and Qi, XQ and Wu, LF}, title = {Pressure-Regulated Gene Expression and Enzymatic Activity of the Two Periplasmic Nitrate Reductases in the Deep-Sea Bacterium Shewanella piezotolerans WP3.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3173}, pmid = {30622525}, issn = {1664-302X}, abstract = {Shewanella species are widely distributed in marine environments, from the shallow coasts to the deepest sea bottom. Most Shewanella species possess two isoforms of periplasmic nitrate reductases (NAP-α and NAP-β) and are able to generate energy through nitrate reduction. However, the contributions of the two NAP systems to bacterial deep-sea adaptation remain unclear. In this study, we found that the deep-sea denitrifier Shewanella piezotolerans WP3 was capable of performing nitrate respiration under high hydrostatic pressure (HHP) conditions. In the wild-type strain, NAP-β played a dominant role and was induced by both the substrate and an elevated pressure, whereas NAP-α was constitutively expressed at a relatively lower level. Genetic studies showed that each NAP system alone was sufficient to fully sustain nitrate-dependent growth and that both NAP systems exhibited substrate and pressure inducible expression patterns when the other set was absent. Biochemical assays further demonstrated that NAP-α had a higher tolerance to elevated pressure. Collectively, we report for the first time the distinct properties and contributions of the two NAP systems to nitrate reduction under different pressure conditions. The results will shed light on the mechanisms of bacterial HHP adaptation and nitrogen cycling in the deep-sea environment.}, } @article {pmid30618841, year = {2018}, author = {Huitzil, S and Sandoval-Motta, S and Frank, A and Aldana, M}, title = {Modeling the Role of the Microbiome in Evolution.}, journal = {Frontiers in physiology}, volume = {9}, number = {}, pages = {1836}, pmid = {30618841}, issn = {1664-042X}, abstract = {There is undeniable evidence showing that bacteria have strongly influenced the evolution and biological functions of multicellular organisms. It has been hypothesized that many host-microbial interactions have emerged so as to increase the adaptive fitness of the holobiont (the host plus its microbiota). Although this association has been corroborated for many specific cases, general mechanisms explaining the role of the microbiota in the evolution of the host are yet to be understood. Here we present an evolutionary model in which a network representing the host adapts in order to perform a predefined function. During its adaptation, the host network (HN) can interact with other networks representing its microbiota. We show that this interaction greatly accelerates and improves the adaptability of the HN without decreasing the adaptation of the microbial networks. Furthermore, the adaptation of the HN to perform several functions is possible only when it interacts with many different bacterial networks in a specialized way (each bacterial network participating in the adaptation of one function). Disrupting these interactions often leads to non-adaptive states, reminiscent of dysbiosis, where none of the networks the holobiont consists of can perform their respective functions. By considering the holobiont as a unit of selection and focusing on the adaptation of the host to predefined but arbitrary functions, our model predicts the need for specialized diversity in the microbiota. This structural and dynamical complexity in the holobiont facilitates its adaptation, whereas a homogeneous (non-specialized) microbiota is inconsequential or even detrimental to the holobiont's evolution. To our knowledge, this is the first model in which symbiotic interactions, diversity, specialization and dysbiosis in an ecosystem emerge as a result of coevolution. It also helps us understand the emergence of complex organisms, as they adapt more easily to perform multiple tasks than non-complex ones.}, } @article {pmid30612623, year = {2019}, author = {Bowman, JL and Briginshaw, LN and Florent, SN}, title = {Evolution and co-option of developmental regulatory networks in early land plants.}, journal = {Current topics in developmental biology}, volume = {131}, number = {}, pages = {35-53}, doi = {10.1016/bs.ctdb.2018.10.001}, pmid = {30612623}, issn = {1557-8933}, mesh = {*Biological Evolution ; Embryophyta/*genetics/*growth & development ; *Gene Expression Regulation, Plant ; *Gene Regulatory Networks ; Plant Proteins/*genetics ; }, abstract = {Land plants evolved from an ancestral alga from which they inherited developmental and physiological characters. A key innovation of land plants is a life cycle with an alternation of generations, with both haploid gametophyte and diploid sporophyte generations having complex multicellular bodies. The origins of the developmental genetic programs patterning these bodies, whether inherited from an algal ancestor or evolved de novo, and whether programs were co-opted between generations, are largely open questions. We first provide a framework for land plant evolution and co-option of developmental regulatory pathways and then examine two cases in more detail.}, } @article {pmid30612620, year = {2019}, author = {Hackenberg, D and Twell, D}, title = {The evolution and patterning of male gametophyte development.}, journal = {Current topics in developmental biology}, volume = {131}, number = {}, pages = {257-298}, doi = {10.1016/bs.ctdb.2018.10.008}, pmid = {30612620}, issn = {1557-8933}, support = {BB/N005090/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; *Gametogenesis, Plant ; *Plant Physiological Phenomena ; *Plants ; Pollen/*cytology/*physiology ; }, abstract = {The reproductive adaptations of land plants have played a key role in their terrestrial colonization and radiation. This encompasses mechanisms used for the production, dispersal and union of gametes to support sexual reproduction. The production of small motile male gametes and larger immotile female gametes (oogamy) in specialized multicellular gametangia evolved in the charophyte algae, the closest extant relatives of land plants. Reliance on water and motile male gametes for sexual reproduction was retained by bryophytes and basal vascular plants, but was overcome in seed plants by the dispersal of pollen and the guided delivery of non-motile sperm to the female gametes. Here we discuss the evolutionary history of male gametogenesis in streptophytes (green plants) and the underlying developmental biology, including recent advances in bryophyte and angiosperm models. We conclude with a perspective on research trends that promise to deliver a deeper understanding of the evolutionary and developmental mechanisms of male gametogenesis in plants.}, } @article {pmid30612613, year = {2019}, author = {Szövényi, P and Waller, M and Kirbis, A}, title = {Evolution of the plant body plan.}, journal = {Current topics in developmental biology}, volume = {131}, number = {}, pages = {1-34}, doi = {10.1016/bs.ctdb.2018.11.005}, pmid = {30612613}, issn = {1557-8933}, mesh = {*Biological Evolution ; Embryophyta/genetics/*growth & development ; Phylogeny ; Plant Leaves/genetics/*growth & development ; Plant Roots/genetics/*growth & development ; }, abstract = {Land plants evolved about 470 million years ago or even earlier, in a biological crust-dominated terrestrial flora. The origin of land plants was probably one of the most significant events in Earth's history, which ultimately contributed to the greening of the terrestrial environment and opened up the way for the diversification of both plant and non-plant lineages. Fossil and phylogenetic evidence suggest that land plants have evolved from fresh-water charophycean algae, which were physiologically, genetically, and developmentally potentiated to make the transition to land. Since all land plants have biphasic life cycles, in contrast to the haplontic life cycle of Charophytes, the evolution of land plants was linked to the origin of a multicellular sporophytic phase. Land plants have evolved complex body plans in a way that overall complexity increased toward the tip of the land plant tree of life. Early forms were unbranched, with terminal sporangia and simple rhizoid rooting structures but without vasculature and leaves. Later on, branched forms with lateral sporangia appeared and paved the route for the evolution for indeterminacy. Finally, leaves and roots evolved to enable efficient nutrient transport to support a large plant body. The fossil record also suggests that almost all plant organs, such as leaves and roots, evolved multiple times independently over the course of land plant evolution. In this review, we summarize the current knowledge on the evolution of the land plant body plan by combining evidence of the fossil record, phylogenetics, and developmental biology.}, } @article {pmid30602438, year = {2019}, author = {Murre, C}, title = {Helix-loop-helix proteins and the advent of cellular diversity: 30 years of discovery.}, journal = {Genes & development}, volume = {33}, number = {1-2}, pages = {6-25}, pmid = {30602438}, issn = {1549-5477}, support = {P01 AI102853/AI/NIAID NIH HHS/United States ; R01 AI082850/AI/NIAID NIH HHS/United States ; Z01 AI000880/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cell Lineage/genetics ; Enhancer Elements, Genetic/physiology ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Helix-Loop-Helix Motifs/physiology ; Promoter Regions, Genetic/physiology ; }, abstract = {Helix-loop-helix (HLH) proteins are dimeric transcription factors that control lineage- and developmental-specific gene programs. Genes encoding for HLH proteins arose in unicellular organisms >600 million years ago and then duplicated and diversified from ancestral genes across the metazoan and plant kingdoms to establish multicellularity. Hundreds of HLH proteins have been identified with diverse functions in a wide variety of cell types. HLH proteins orchestrate lineage specification, commitment, self-renewal, proliferation, differentiation, and homing. HLH proteins also regulate circadian clocks, protect against hypoxic stress, promote antigen receptor locus assembly, and program transdifferentiation. HLH proteins deposit or erase epigenetic marks, activate noncoding transcription, and sequester chromatin remodelers across the chromatin landscape to dictate enhancer-promoter communication and somatic recombination. Here the evolution of HLH genes, the structures of HLH domains, and the elaborate activities of HLH proteins in multicellular life are discussed.}, } @article {pmid30590727, year = {2019}, author = {Tsitsekian, D and Daras, G and Alatzas, A and Templalexis, D and Hatzopoulos, P and Rigas, S}, title = {Comprehensive analysis of Lon proteases in plants highlights independent gene duplication events.}, journal = {Journal of experimental botany}, volume = {70}, number = {7}, pages = {2185-2197}, pmid = {30590727}, issn = {1460-2431}, mesh = {Base Sequence ; *Evolution, Molecular ; *Gene Duplication ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Plants/*genetics/metabolism ; Protease La/*genetics/metabolism ; Sequence Alignment ; }, abstract = {The degradation of damaged proteins is essential for cell viability. Lon is a highly conserved ATP-dependent serine-lysine protease that maintains proteostasis. We performed a comparative genome-wide analysis to determine the evolutionary history of Lon proteases. Prokaryotes and unicellular eukaryotes retained a single Lon copy, whereas multicellular eukaryotes acquired a peroxisomal copy, in addition to the mitochondrial gene, to sustain the evolution of higher order organ structures. Land plants developed small Lon gene families. Despite the Lon2 peroxisomal paralog, Lon genes triplicated in the Arabidopsis lineage through sequential evolutionary events including whole-genome and tandem duplications. The retention of Lon1, Lon4, and Lon3 triplicates relied on their differential and even contrasting expression patterns, distinct subcellular targeting mechanisms, and functional divergence. Lon1 seems similar to the pre-duplication ancestral gene unit, whereas the duplication of Lon3 and Lon4 is evolutionarily recent. In the wider context of plant evolution, papaya is the only genome with a single ancestral Lon1-type gene. The evolutionary trend among plants is to acquire Lon copies with ambiguous pre-sequences for dual-targeting to mitochondria and chloroplasts, and a substrate recognition domain that deviates from the ancestral Lon1 type. Lon genes constitute a paradigm of dynamic evolution contributing to understanding the functional fate of gene duplicates.}, } @article {pmid30590062, year = {2019}, author = {Måløy, M and Måløy, F and Lahoz-Beltrá, R and Carlos Nuño, J and Bru, A}, title = {An extended Moran process that captures the struggle for fitness.}, journal = {Mathematical biosciences}, volume = {308}, number = {}, pages = {81-104}, doi = {10.1016/j.mbs.2018.12.014}, pmid = {30590062}, issn = {1879-3134}, mesh = {Animals ; *Biological Evolution ; *Environment ; *Game Theory ; Humans ; *Models, Biological ; *Population Dynamics ; Stochastic Processes ; }, abstract = {When a new type of individual appears in a stable population, the newcomer is typically not advantageous. Due to stochasticity, the new type can grow in numbers, but the newcomers can only become advantageous if they manage to change the environment in such a way that they increase their fitness. This dynamics is observed in several situations in which a relatively stable population is invaded by an alternative strategy, for instance the evolution of cooperation among bacteria, the invasion of cancer in a multicellular organism and the evolution of ideas that contradict social norms. These examples also show that, by generating different versions of itself, the new type increases the probability of winning the struggle for fitness. Our model captures the imposed cooperation whereby the first generation of newcomers dies while changing the environment such that the next generations become more advantageous.}, } @article {pmid30585312, year = {2019}, author = {Denbo, S and Aono, K and Kai, T and Yagasaki, R and Ruiz-Trillo, I and Suga, H}, title = {Revision of the Capsaspora genome using read mating information adjusts the view on premetazoan genome.}, journal = {Development, growth & differentiation}, volume = {61}, number = {1}, pages = {34-42}, doi = {10.1111/dgd.12587}, pmid = {30585312}, issn = {1440-169X}, support = {16K07468//JSPS KAKENHI/ ; //NOVARTIS Foundation/ ; //ITOH Science Foundation/ ; //Naito Foundation/ ; //Prefectural University of Hiroshima JUTEN Grant/ ; ERC-2012-Co-616960//European Research Council Consolidator Grant/ ; BFU2014-57779-P//European Research Council Consolidator Grant/ ; BFU2017-90114-P//European Research Council Consolidator Grant/ ; //Ministerio de Economía y Competitividad (MINECO)/ ; //Agencia Estatal de Investigación (AEI)/ ; //Fondo Europeo de Desarrollo Regional (FEDER)/ ; }, mesh = {Animals ; Chromosomes/genetics ; Eukaryota/enzymology/*genetics/metabolism ; Genome/*genetics ; Phylogeny ; Protein-Tyrosine Kinases/genetics ; }, abstract = {The genome sequences of unicellular holozoans, the closest relatives to animals, are shedding light on the evolution of animal multicellularity, shaping the genetic contents of the putative premetazoans. However, the assembly quality of the genomes remains poor compared to the major model organisms such as human and fly. Improving the assembly is critical for precise comparative genomics studies and further molecular biological studies requiring accurate sequence information such as enhancer analysis and genome editing. In this report, we present a new strategy to improve the assembly by fully exploiting the information of Illumina mate-pair reads. By visualizing the distance and orientation of the mapped read pairs, we could highlight the regions where possible assembly errors exist in the genome sequence of Capsaspora, a lineage of unicellular holozoans. Manual modification of these errors repaired 590 assembly problems in total and reassembled 84 supercontigs into 55. Our telomere prediction analysis using the read pairs containing the pan-eukaryotic telomere-like sequence identified at least 13 chromosomes. The resulting new assembly posed us a re-annotation of 112 genes, including 15 putative receptor protein tyrosine kinases. Our strategy thus provides a useful approach for improving assemblies of draft genomes, and the new Capsaspora genome offers us an opportunity to adjust the view on the genome of the unicellular animal ancestor.}, } @article {pmid30578282, year = {2019}, author = {Zhao, YG and Zhang, H}, title = {Autophagosome maturation: An epic journey from the ER to lysosomes.}, journal = {The Journal of cell biology}, volume = {218}, number = {3}, pages = {757-770}, pmid = {30578282}, issn = {1540-8140}, mesh = {Animals ; *Autophagic Cell Death ; Autophagosomes/*metabolism/pathology ; Biological Transport, Active ; Endoplasmic Reticulum/*metabolism/pathology ; Humans ; Lysosomes/*metabolism/pathology ; Neurodegenerative Diseases/*metabolism/pathology ; }, abstract = {Macroautophagy involves the sequestration of cytoplasmic contents in a double-membrane autophagosome and their delivery to lysosomes for degradation. In multicellular organisms, nascent autophagosomes fuse with vesicles originating from endolysosomal compartments before forming degradative autolysosomes, a process known as autophagosome maturation. ATG8 family members, tethering factors, Rab GTPases, and SNARE proteins act coordinately to mediate fusion of autophagosomes with endolysosomal vesicles. The machinery mediating autophagosome maturation is under spatiotemporal control and provides regulatory nodes to integrate nutrient availability with autophagy activity. Dysfunction of autophagosome maturation is associated with various human diseases, including neurodegenerative diseases, Vici syndrome, cancer, and lysosomal storage disorders. Understanding the molecular mechanisms underlying autophagosome maturation will provide new insights into the pathogenesis and treatment of these diseases.}, } @article {pmid30576875, year = {2019}, author = {Ortega-Escalante, JA and Kwok, O and Miller, SM}, title = {New Selectable Markers for Volvox carteri Transformation.}, journal = {Protist}, volume = {170}, number = {1}, pages = {52-63}, doi = {10.1016/j.protis.2018.11.002}, pmid = {30576875}, issn = {1618-0941}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacillus cereus/genetics ; Cinnamates/*pharmacology ; Coccidioides/genetics ; Drug Resistance, Microbial/*genetics ; Genes, Bacterial/genetics ; Genes, Fungal/genetics ; Genetic Markers/genetics ; Hygromycin B/*analogs & derivatives/pharmacology ; Microorganisms, Genetically-Modified/genetics ; Nucleosides/pharmacology ; Transformation, Genetic/drug effects/*genetics ; Volvox/drug effects/*genetics ; }, abstract = {Volvox carteri is an excellent model for investigating the evolution of multicellularity and cell differentiation, and the rate of future progress with this system will depend on improved molecular genetic tools. Several selectable markers for nuclear transformation of V. carteri have been developed, including the nitrate reductase (nitA) gene, but it would be useful to have additional markers to multiplex transgenes in this species. To further facilitate molecular genetic analyses of V. carteri, we developed two new selectable markers that provide rapid, easily selected, and stable resistance to the antibiotics hygromycin and blasticidin. We generated constructs with Volvox-specific regulatory sequences and codon-optimized hygromycin (VcHyg) and blasticidin (VcBlast) resistance genes from Coccidioides posadasii and Bacillus cereus, respectively. With these constructs, transformants were obtained via biolistic bombardment at rates of 0.5-13 per million target cells bombarded. Antibiotic-resistant survivors were readily isolated 7days post bombardment. VcHyg and VcBlast transgenes and transcripts were detected in transformants. Co-transformation rates using the VcHyg or VcBlast markers with unselected genes were comparable to those obtained with nitA. These results indicate that the pVcHyg and pVcBlast plasmids are highly efficient and convenient for transforming and co-transforming a broad range of V. carteri strains.}, } @article {pmid30568302, year = {2019}, author = {Chen, Y and Ikeda, K and Yoneshiro, T and Scaramozza, A and Tajima, K and Wang, Q and Kim, K and Shinoda, K and Sponton, CH and Brown, Z and Brack, A and Kajimura, S}, title = {Thermal stress induces glycolytic beige fat formation via a myogenic state.}, journal = {Nature}, volume = {565}, number = {7738}, pages = {180-185}, pmid = {30568302}, issn = {1476-4687}, support = {P30 DK063720/DK/NIDDK NIH HHS/United States ; R01 DK097441/DK/NIDDK NIH HHS/United States ; R01 DK108822/DK/NIDDK NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; P30 DK026687/DK/NIDDK NIH HHS/United States ; R01 DK112268/DK/NIDDK NIH HHS/United States ; }, mesh = {Acclimatization ; Adipose Tissue, Beige/*cytology/*metabolism ; Adipose Tissue, White/cytology/metabolism ; Animals ; Cell Differentiation ; Cell Survival ; *Cold Temperature ; *Cold-Shock Response ; Energy Metabolism ; GA-Binding Protein Transcription Factor/metabolism ; *Glycolysis ; Homeostasis ; Male ; Mice ; *Muscle Development ; MyoD Protein/metabolism ; Myoblasts/cytology ; Receptors, Adrenergic, beta/metabolism ; }, abstract = {Environmental cues profoundly affect cellular plasticity in multicellular organisms. For instance, exercise promotes a glycolytic-to-oxidative fibre-type switch in skeletal muscle, and cold acclimation induces beige adipocyte biogenesis in adipose tissue. However, the molecular mechanisms by which physiological or pathological cues evoke developmental plasticity remain incompletely understood. Here we report a type of beige adipocyte that has a critical role in chronic cold adaptation in the absence of β-adrenergic receptor signalling. This beige fat is distinct from conventional beige fat with respect to developmental origin and regulation, and displays enhanced glucose oxidation. We therefore refer to it as glycolytic beige fat. Mechanistically, we identify GA-binding protein α as a regulator of glycolytic beige adipocyte differentiation through a myogenic intermediate. Our study reveals a non-canonical adaptive mechanism by which thermal stress induces progenitor cell plasticity and recruits a distinct form of thermogenic cell that is required for energy homeostasis and survival.}, } @article {pmid30564256, year = {2018}, author = {Solórzano-Cascante, P and Sánchez-Chiang, N and Jiménez, VM}, title = {Explant Type, Culture System, 6-Benzyladenine, Meta-Topolin and Encapsulation Affect Indirect Somatic Embryogenesis and Regeneration in Carica papaya L.}, journal = {Frontiers in plant science}, volume = {9}, number = {}, pages = {1769}, pmid = {30564256}, issn = {1664-462X}, abstract = {A protocol to propagate papaya hybrid plants through indirect somatic embryogenesis was developed considering the effect of explant type, culture system, particular cytokinins and encapsulation, in different stages of the process. Optimal 2,4-dichlorophenoxyacetic acid (2,4-D) concentrations for non-embryogenic callus formation ranged between 9.0 and 27.1 μM in half-cut seeds, while higher concentrations were harmful. Non-embryogenic callus was also obtained with 22-158 μM 2,4-D from hypocotyl segments. Callus with embryogenic structures was only obtained in half-cut seeds cultured in the darkness on half-strength Murashige and Skoog culture medium supplemented with 2,4-D, while hypocotyl segments and isolated zygotic embryos failed to produce this type of callus regardless of the 2,4-D and sucrose (30 and 70 g l[-1]) concentrations tested in this study. Both, embryogenic callus development and quantity of somatic embryos formed per embryogenic callus, which ranged between 11 and 31 units after 14 months, required 2,4-D, but without any effect of the concentration. Histological studies confirmed the multicellular origin of the somatic embryos. In further steps, liquid medium induced over four times more somatic embryos than agar-gelled medium and showed significantly higher production of globular somatic embryos (85 vs. 57%). Both, 6-benzyladenine (BA) and meta-topolin (Mtop) stimulated sprouting (40-45%) of the somatic embryos (development of shoots only) in concentrations of up to 2.7 and 10 μM, respectively. Sprouting probability showed a 2nd order polynomial trend despite the range of concentration used for each cytokinin. This is the first report about the positive effect of Mtop on the apical shoot development of Carica papaya somatic embryos known to the authors. Radicle growth was observed in 5% or less of the cultivated embryos, regardless of the BA concentration. Finally, all encapsulation conditions tested (2.5, 3.5, and 4.5% sodium alginate, combined with 50 and 100 mM CaCl2) reduced sprouting of somatic embryos when compared to the non-encapsulated ones, whereas capsule hardness showed low correlation with embryo sprouting. Embryos were further cultivated until they became plantlets approximately 5 cm long. They were acclimatized and afterward planted in the field, where they flowered and produced fruit.}, } @article {pmid30563248, year = {2018}, author = {Wang, Z and Zhou, W and Hameed, MS and Liu, J and Zeng, X}, title = {Characterization and Expression Profiling of Neuropeptides and G-Protein-Coupled Receptors (GPCRs) for Neuropeptides in the Asian Citrus Psyllid, Diaphorina citri (Hemiptera: Psyllidae).}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, pmid = {30563248}, issn = {1422-0067}, support = {31572314//National Natural Science Foundation of China/ ; 2017YFD0202005//National Key Research and Development Program of China/ ; 2015B090903076//Department of Science and Technology of Guangdong Province/ ; }, mesh = {Animals ; Citrus/*parasitology ; Evolution, Molecular ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Developmental ; Hemiptera/genetics/*growth & development ; Insect Proteins/genetics ; Neuropeptides/*genetics ; Organ Specificity ; Phylogeny ; Real-Time Polymerase Chain Reaction ; Receptors, G-Protein-Coupled/*genetics ; Sequence Analysis, RNA ; }, abstract = {Neuropeptides are endogenous active substances that widely exist in multicellular biological nerve tissue and participate in the function of the nervous system, and most of them act on neuropeptide receptors. In insects, neuropeptides and their receptors play important roles in controlling a multitude of physiological processes. In this project, we sequenced the transcriptome from twelve tissues of the Asian citrus psyllid, Diaphorina citri Kuwayama. A total of 40 candidate neuropeptide genes and 42 neuropeptide receptor genes were identified. Among the neuropeptide receptor genes, 35 of them belong to the A-family (or rhodopsin-like), four of them belong to the B-family (or secretin-like), and three of them are leucine-rich repeat-containing G-protein-coupled receptors. The expression profile of the 82 genes across developmental stages was determined by qRT-PCR. Our study provides the first investigation on the genes of neuropeptides and their receptors in D. citri, which may play key roles in regulating the physiology and behaviors of D. citri.}, } @article {pmid30560372, year = {2019}, author = {Dadar, M and Shahali, Y and Chakraborty, S and Prasad, M and Tahoori, F and Tiwari, R and Dhama, K}, title = {Antiinflammatory peptides: current knowledge and promising prospects.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {68}, number = {2}, pages = {125-145}, pmid = {30560372}, issn = {1420-908X}, mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Humans ; Immune System/physiology ; Inflammation/complications/*drug therapy/*physiopathology ; Peptides/*pharmacology/*physiology ; }, abstract = {BACKGROUND: Inflammation is part of the regular host reaction to injury or infection caused by toxic factors, pathogens, damaged cells, irritants, and allergens. Antiinflammatory peptides (AIPs) are present in all living organisms, and many peptides from herbal, mammalian, bacterial, and marine origins have been shown to have antimicrobial and/or antiinflammatory properties.

METHODS: In this study, we investigated the effects of antiinflammatory peptides on inflammation, and highlighted the underlying mechanisms responsible for these effects.

RESULTS: In multicellular organisms, including humans, AIPs constitute an essential part of their immune system. In addition, numerous natural and synthetic AIPs are effective immunomodulators and can interfere with signal transduction pathways involved in inflammatory cytokine expression. Among them, some peptides such as antiflammin, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), and those derived from velvet antler proteins, bee venom, horse fly salivary gland, and bovine β-casein have received considerable attention over the past few years.

CONCLUSION: This article presents an overview on the major properties and mechanisms of action associated with AIPs as immunomodulatory, chemotactic, antioxidant, and antimicrobial agents. In addition, the results of various studies dealing with effects of AIPs on numerous classical models of inflammation are reviewed and discussed.}, } @article {pmid30558164, year = {2018}, author = {Millán, I and Piñero-Ramos, JD and Lara, I and Parra-Llorca, A and Torres-Cuevas, I and Vento, M}, title = {Oxidative Stress in the Newborn Period: Useful Biomarkers in the Clinical Setting.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {7}, number = {12}, pages = {}, pmid = {30558164}, issn = {2076-3921}, support = {PI17/0131//Instituto de Investigación en Salud Carlos III/ ; APOSTD/2018/A/172//CONSELLERIA EDUCAÇIÓ, INVESTIGAÇIÓ, CULTURA I ESPORT/ ; }, abstract = {Aerobic metabolism is highly efficient in providing energy for multicellular organisms. However, even under physiological conditions, an incomplete reduction of oxygen produces reactive oxygen species and, subsequently, oxidative stress. Some of these chemical species are highly reactive free radicals capable of causing functional and structural damage to cell components (protein, lipids, or nucleotides). Oxygen is the most used drug in ill-adapted patients during the newborn period. The use of oxygen may cause oxidative stress-related diseases that increase mortality and cause morbidity with adverse long-term outcomes. Conditions such as prematurity or birth asphyxia are frequently treated with oxygen supplementation. Both pathophysiological situations of hypoxia[-]reoxygenation in asphyxia and hyperoxia in premature infants cause a burst of reactive oxygen species and oxidative stress. Recently developed analytical assays using mass spectrometry have allowed us to determine highly specific biomarkers with minimal samples. The detection of these metabolites will help improve the diagnosis, evolution, and response to therapy in oxidative stress-related conditions during the newborn period.}, } @article {pmid30554805, year = {2019}, author = {Stein, WD}, title = {The ages of the cancer-associated genes.}, journal = {Seminars in oncology}, volume = {46}, number = {1}, pages = {10-18}, doi = {10.1053/j.seminoncol.2018.11.001}, pmid = {30554805}, issn = {1532-8708}, mesh = {Carcinoma/genetics ; *Evolution, Molecular ; Genome, Human/*genetics ; Humans ; Lymphoma/genetics ; Mutation/genetics ; Neoplasms/*genetics/pathology ; Open Reading Frames/*genetics ; Sarcoma/genetics ; }, abstract = {In the accompanying manuscript (Litman and Stein, 2018) we list the ages of all the protein-coding genes and of many of the noncoding genes of the human genome. The present manuscript uses those results to derive the ages of the genes on the COSMIC list of somatic mutations in cancer. The lymphoma-associated genes in the COSMIC list are younger than the sarcoma-associated or the carcinoma-associated genes, or the genes shared by lymphomas and carcinomas. Genes that accreted to the evolving genome with the appearance of the fish are major contributors to the sarcoma-, lymphoma-, or carcinoma-associated gene sets, but it is genes accreted during the development of multicellularity that contribute most to the genes common to the classes. Genes arising with the evolution of the fish are also dominant in a list of noncoding genes associated with cancer. A list is provided of the COSMIC genes which have not yet been reported as drug targets.}, } @article {pmid30553725, year = {2018}, author = {Taggart, JC and Li, GW}, title = {Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes.}, journal = {Cell systems}, volume = {7}, number = {6}, pages = {580-589.e4}, pmid = {30553725}, issn = {2405-4712}, support = {R35 GM124732/GM/NIGMS NIH HHS/United States ; T32 GM007287/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Multiprotein Complexes/genetics/*metabolism ; *Protein Biosynthesis ; Protein Subunits/genetics/metabolism ; Ribosomes/genetics/*metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Zebrafish ; }, abstract = {Constituents of multiprotein complexes are required at well-defined levels relative to each other. However, it remains unknown whether eukaryotic cells typically produce precise amounts of subunits, or instead rely on degradation to mitigate imprecise production. Here, we quantified the production rates of multiprotein complexes in unicellular and multicellular eukaryotes using ribosome profiling. By resolving read-mapping ambiguities, which occur for a large fraction of ribosome footprints and distort quantitation accuracy in eukaryotes, we found that obligate components of multiprotein complexes are produced in proportion to their stoichiometry, indicating that their abundances are already precisely tuned at the synthesis level. By systematically interrogating the impact of gene dosage variations in budding yeast, we found a general lack of negative feedback regulation protecting the normally precise rates of subunit synthesis. These results reveal a core principle of proteome homeostasis and highlight the evolution toward quantitative control at every step in the central dogma.}, } @article {pmid30545356, year = {2018}, author = {Herron, MD and Zamani-Dahaj, SA and Ratcliff, WC}, title = {Trait heritability in major transitions.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {145}, pmid = {30545356}, issn = {1741-7007}, mesh = {*Biological Evolution ; *Heredity ; Models, Genetic ; *Phenotype ; Selection, Genetic ; }, abstract = {BACKGROUND: Increases in biological complexity and the origins of life's hierarchical organization are described by the "major transitions" framework. A crucial component of this paradigm is that after the transition in complexity or organization, adaptation occurs primarily at the level of the new, higher-level unit. For collective-level adaptations to occur, though, collective-level traits-properties of the group, such as collective size-must be heritable. Since collective-level trait values are functions of lower-level trait values, collective-level heritability is related to particle-level heritability. However, the nature of this relationship has rarely been explored in the context of major transitions.

RESULTS: We examine relationships between particle-level heritability and collective-level heritability for several functions that express collective-level trait values in terms of particle-level trait values. For clonal populations, when a collective-level trait value is a linear function of particle-level trait values and the number of particles per collective is fixed, the heritability of a collective-level trait is never less than that of the corresponding particle-level trait and is higher under most conditions. For more complicated functions, collective-level heritability is higher under most conditions, but can be lower when the environment experienced by collectives is heterogeneous. Within-genotype variation in collective size reduces collective-level heritability, but it can still exceed particle-level heritability when phenotypic variance among particles within collectives is large. These results hold for a diverse sample of biologically relevant traits.

CONCLUSIONS: Rather than being an impediment to major transitions, we show that, under a wide range of conditions, the heritability of collective-level traits is actually higher than that of the corresponding particle-level traits. High levels of collective-level trait heritability thus arise "for free," with important implications not only for major transitions but for multilevel selection in general.}, } @article {pmid30541961, year = {2018}, author = {Hayakawa, IS and Inouye, K}, title = {Species recognition in social amoebae.}, journal = {Journal of biosciences}, volume = {43}, number = {5}, pages = {1025-1036}, pmid = {30541961}, issn = {0973-7138}, mesh = {Biological Evolution ; Dictyostelium/classification/*genetics ; *Genes, Protozoan ; *Genome, Protozoan ; Phylogeny ; Reproduction ; Species Specificity ; }, abstract = {Aggregative multicellularity requires the ability of cells to recognise conspecifics. Social amoebae are among the best studied of such organisms, but the mechanism and evolutionary background of species recognition remained to be investigated. Here we show that heterologous expression of a single Dictyostelium purpureum gene is sufficient for D. discoideum cells to efficiently make chimaeric fruiting bodies with D. purpureum cells. This gene forms a bidirectional pair with another gene on the D. purpureum genome, and they are both highly polymorphic among independent wild isolates of the same mating group that do not form chimaeric fruiting bodies with each other. These paired genes are both structurally similar to D. discoideum tgrB1/C1 pair, which is responsible for clonal discrimination within that species, suggesting that these tgr genes constitute the species recognition system that has attained a level of precision capable of discriminating between clones within a species. Analysis of the available genome sequences of social amoebae revealed that such gene pairs exist only within the clade composed of species that produce precursors of sterile stalk cells (prestalk cells), suggesting concurrent evolution of a precise allorecognition system and a new 'worker' cell-type dedicated to transporting and supporting the reproductive cells.}, } @article {pmid30538242, year = {2018}, author = {Higo, A and Kawashima, T and Borg, M and Zhao, M and López-Vidriero, I and Sakayama, H and Montgomery, SA and Sekimoto, H and Hackenberg, D and Shimamura, M and Nishiyama, T and Sakakibara, K and Tomita, Y and Togawa, T and Kunimoto, K and Osakabe, A and Suzuki, Y and Yamato, KT and Ishizaki, K and Nishihama, R and Kohchi, T and Franco-Zorrilla, JM and Twell, D and Berger, F and Araki, T}, title = {Transcription factor DUO1 generated by neo-functionalization is associated with evolution of sperm differentiation in plants.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {5283}, pmid = {30538242}, issn = {2041-1723}, support = {M 2539/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Cell Differentiation ; Chlorophyta/classification/genetics/growth & development/metabolism ; *Evolution, Molecular ; Germ Cells, Plant/*cytology/metabolism ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Plants/classification/genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Evolutionary mechanisms underlying innovation of cell types have remained largely unclear. In multicellular eukaryotes, the evolutionary molecular origin of sperm differentiation is unknown in most lineages. Here, we report that in algal ancestors of land plants, changes in the DNA-binding domain of the ancestor of the MYB transcription factor DUO1 enabled the recognition of a new cis-regulatory element. This event led to the differentiation of motile sperm. After neo-functionalization, DUO1 acquired sperm lineage-specific expression in the common ancestor of land plants. Subsequently the downstream network of DUO1 was rewired leading to sperm with distinct morphologies. Conjugating green algae, a sister group of land plants, accumulated mutations in the DNA-binding domain of DUO1 and lost sperm differentiation. Our findings suggest that the emergence of DUO1 was the defining event in the evolution of sperm differentiation and the varied modes of sexual reproduction in the land plant lineage.}, } @article {pmid30533723, year = {2018}, author = {Ducluzeau, AL and Tyson, JR and Collins, RE and Snutch, TP and Hassett, BT}, title = {Genome Sequencing of Sub-Arctic Mesomycetozoean Sphaeroforma sirkka Strain B5, Performed with the Oxford Nanopore minION and Illumina HiSeq Systems.}, journal = {Microbiology resource announcements}, volume = {7}, number = {15}, pages = {}, pmid = {30533723}, issn = {2576-098X}, abstract = {The Mesomycetozoea branch near the animal-fungal divergence and are believed to be important to understanding the origins of multicellularity. In 2012, a free-living saprotrophic mesomycetozoean was isolated from the sub-Arctic Bering Sea. A hybrid assembly using Illumina and Nanopore sequences yielded 2,688 contigs with a total length of 125,635,304 bases.}, } @article {pmid30532226, year = {2018}, author = {Shan, M and Dai, D and Vudem, A and Varner, JD and Stroock, AD}, title = {Multi-scale computational study of the Warburg effect, reverse Warburg effect and glutamine addiction in solid tumors.}, journal = {PLoS computational biology}, volume = {14}, number = {12}, pages = {e1006584}, pmid = {30532226}, issn = {1553-7358}, mesh = {Cell Line, Tumor ; Cell Proliferation ; Citric Acid Cycle/physiology ; Glucose/metabolism ; Glutamine/*metabolism ; Glycolysis/*physiology ; Humans ; Kinetics ; Lactic Acid/metabolism ; Metabolic Networks and Pathways/physiology ; Metabolome ; Neoplasms/metabolism ; Oxygen/metabolism ; Tumor Microenvironment/*physiology ; }, abstract = {Cancer metabolism has received renewed interest as a potential target for cancer therapy. In this study, we use a multi-scale modeling approach to interrogate the implications of three metabolic scenarios of potential clinical relevance: the Warburg effect, the reverse Warburg effect and glutamine addiction. At the intracellular level, we construct a network of central metabolism and perform flux balance analysis (FBA) to estimate metabolic fluxes; at the cellular level, we exploit this metabolic network to calculate parameters for a coarse-grained description of cellular growth kinetics; and at the multicellular level, we incorporate these kinetic schemes into the cellular automata of an agent-based model (ABM), iDynoMiCS. This ABM evaluates the reaction-diffusion of the metabolites, cellular division and motion over a simulation domain. Our multi-scale simulations suggest that the Warburg effect provides a growth advantage to the tumor cells under resource limitation. However, we identify a non-monotonic dependence of growth rate on the strength of glycolytic pathway. On the other hand, the reverse Warburg scenario provides an initial growth advantage in tumors that originate deeper in the tissue. The metabolic profile of stromal cells considered in this scenario allows more oxygen to reach the tumor cells in the deeper tissue and thus promotes tumor growth at earlier stages. Lastly, we suggest that glutamine addiction does not confer a selective advantage to tumor growth with glutamine acting as a carbon source in the tricarboxylic acid (TCA) cycle, any advantage of glutamine uptake must come through other pathways not included in our model (e.g., as a nitrogen donor). Our analysis illustrates the importance of accounting explicitly for spatial and temporal evolution of tumor microenvironment in the interpretation of metabolic scenarios and hence provides a basis for further studies, including evaluation of specific therapeutic strategies that target metabolism.}, } @article {pmid30532131, year = {2018}, author = {Khasin, M and Cahoon, RR and Nickerson, KW and Riekhof, WR}, title = {Molecular machinery of auxin synthesis, secretion, and perception in the unicellular chlorophyte alga Chlorella sorokiniana UTEX 1230.}, journal = {PloS one}, volume = {13}, number = {12}, pages = {e0205227}, pmid = {30532131}, issn = {1932-6203}, mesh = {Biological Transport, Active/physiology ; Chlorella/genetics/*metabolism ; *Evolution, Molecular ; Indoleacetic Acids/*metabolism ; Plant Proteins/genetics/*metabolism ; Receptors, Cell Surface/genetics/*metabolism ; Signal Transduction/*physiology ; }, abstract = {Indole-3-acetic acid is a ubiquitous small molecule found in all domains of life. It is the predominant and most active auxin in seed plants, where it coordinates a variety of complex growth and development processes. The potential origin of auxin signaling in algae remains a matter of some controversy. In order to clarify the evolutionary context of algal auxin signaling, we undertook a genomic survey to assess whether auxin acts as a signaling molecule in the emerging model chlorophyte Chlorella sorokiniana UTEX 1230. C. sorokiniana produces the auxin indole-3-acetic acid (IAA), which was present in both the cell pellet and in the supernatant at a concentration of ~ 1 nM, and its genome encodes orthologs of genes related to auxin synthesis, transport, and signaling in higher plants. Candidate orthologs for the canonical AUX/IAA signaling pathway were not found; however, auxin-binding protein 1 (ABP1), an alternate auxin receptor, is present and highly conserved at essential auxin binding and zinc coordinating residues. Additionally, candidate orthologs for PIN proteins, responsible for intercellular, vectorial auxin transport in higher plants, were not found, but PILs (PIN-Like) proteins, a recently discovered family that mediates intracellular auxin transport, were identified. The distribution of auxin related gene in this unicellular chlorophyte demonstrates that a core suite of auxin signaling components was present early in the evolution of plants. Understanding the simplified auxin signaling pathways in chlorophytes will aid in understanding phytohormone signaling and crosstalk in seed plants, and in understanding the diversification and integration of developmental signals during the evolution of multicellular plants.}, } @article {pmid30520011, year = {2019}, author = {Rebolleda-Gómez, M and Travisano, M}, title = {Adaptation, chance, and history in experimental evolution reversals to unicellularity.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {73-83}, pmid = {30520011}, issn = {1558-5646}, support = {//John Templeton Foundation/International ; 1051115//Division of Environmental Biology/International ; }, mesh = {*Adaptation, Biological ; *Biological Evolution ; Saccharomyces cerevisiae/*physiology ; }, abstract = {Evolution is often deemed irreversible. The evolution of complex traits that require many mutations makes their reversal unlikely. Even in simpler traits, reversals might become less likely as neutral or beneficial mutations, with deleterious effects in the ancestral context, become fixed in the novel background. This is especially true in changes that involve large reorganizations of the organism and its interactions with the environment. The evolution of multicellularity involves the reorganization of previously autonomous cells into a more complex organism; despite the complexity of this change, single cells have repeatedly evolved from multicellular ancestors. These repeated reversals to unicellularity undermine the generality of Dollo's law. In this article, we evaluated the dynamics of reversals to unicellularity from recently evolved multicellular phenotypes of the brewers yeast Saccharomyces cerevisae. Even though multicellularity in this system evolved recently, it involves the evolution of new levels of selection. Strong selective pressures against multicellularity lead to rapid reversibility to single cells in all of our replicate lines, whereas counterselection favoring multicellularity led to minimal reductions to the rates of reversal. History and chance played an important role in the tempo and mode of reversibility, highlighting the interplay of deterministic and stochastic events in evolutionary reversals.}, } @article {pmid30519187, year = {2018}, author = {Fux, JE and Mehta, A and Moffat, J and Spafford, JD}, title = {Eukaryotic Voltage-Gated Sodium Channels: On Their Origins, Asymmetries, Losses, Diversification and Adaptations.}, journal = {Frontiers in physiology}, volume = {9}, number = {}, pages = {1406}, pmid = {30519187}, issn = {1664-042X}, abstract = {The appearance of voltage-gated, sodium-selective channels with rapid gating kinetics was a limiting factor in the evolution of nervous systems. Two rounds of domain duplications generated a common 24 transmembrane segment (4 × 6 TM) template that is shared amongst voltage-gated sodium (Nav1 and Nav2) and calcium channels (Cav1, Cav2, and Cav3) and leak channel (NALCN) plus homologs from yeast, different single-cell protists (heterokont and unikont) and algae (green and brown). A shared architecture in 4 × 6 TM channels include an asymmetrical arrangement of extended extracellular L5/L6 turrets containing a 4-0-2-2 pattern of cysteines, glycosylated residues, a universally short III-IV cytoplasmic linker and often a recognizable, C-terminal PDZ binding motif. Six intron splice junctions are conserved in the first domain, including a rare U12-type of the minor spliceosome provides support for a shared heritage for sodium and calcium channels, and a separate lineage for NALCN. The asymmetrically arranged pores of 4x6 TM channels allows for a changeable ion selectivity by means of a single lysine residue change in the high field strength site of the ion selectivity filter in Domains II or III. Multicellularity and the appearance of systems was an impetus for Nav1 channels to adapt to sodium ion selectivity and fast ion gating. A non-selective, and slowly gating Nav2 channel homolog in single cell eukaryotes, predate the diversification of Nav1 channels from a basal homolog in a common ancestor to extant cnidarians to the nine vertebrate Nav1.x channel genes plus Nax. A close kinship between Nav2 and Nav1 homologs is evident in the sharing of most (twenty) intron splice junctions. Different metazoan groups have lost their Nav1 channel genes altogether, while vertebrates rapidly expanded their gene numbers. The expansion in vertebrate Nav1 channel genes fills unique functional niches and generates overlapping properties contributing to redundancies. Specific nervous system adaptations include cytoplasmic linkers with phosphorylation sites and tethered elements to protein assemblies in First Initial Segments and nodes of Ranvier. Analogous accessory beta subunit appeared alongside Nav1 channels within different animal sub-phyla. Nav1 channels contribute to pace-making as persistent or resurgent currents, the former which is widespread across animals, while the latter is a likely vertebrate adaptation.}, } @article {pmid30518860, year = {2018}, author = {Rosental, B and Kowarsky, M and Seita, J and Corey, DM and Ishizuka, KJ and Palmeri, KJ and Chen, SY and Sinha, R and Okamoto, J and Mantalas, G and Manni, L and Raveh, T and Clarke, DN and Tsai, JM and Newman, AM and Neff, NF and Nolan, GP and Quake, SR and Weissman, IL and Voskoboynik, A}, title = {Complex mammalian-like haematopoietic system found in a colonial chordate.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {425-429}, pmid = {30518860}, issn = {1476-4687}, support = {T32 AI007290/AI/NIAID NIH HHS/United States ; R01 AG037968/AG/NIA NIH HHS/United States ; T32 AR050942/AR/NIAMS NIH HHS/United States ; T32HL120824-03/HL/NHLBI NIH HHS/United States ; R01 GM100315/GM/NIGMS NIH HHS/United States ; R56 AI089968/AI/NIAID NIH HHS/United States ; T32 HL120824/HL/NHLBI NIH HHS/United States ; 5T32AI07290-28/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Cell Lineage ; Cytotoxicity, Immunologic ; Female ; Flow Cytometry ; *Hematopoiesis ; Hematopoietic Stem Cells/cytology/immunology ; Hematopoietic System/*cytology ; Immunity, Cellular ; Isoantigens/immunology ; Male ; Mammals/anatomy & histology/*blood ; Myeloid Cells/cytology/immunology ; Phagocytosis/immunology ; *Phylogeny ; Stem Cell Niche ; Transcriptome/genetics ; Urochordata/anatomy & histology/*cytology/genetics/immunology ; }, abstract = {Haematopoiesis is an essential process that evolved in multicellular animals. At the heart of this process are haematopoietic stem cells (HSCs), which are multipotent and self-renewing, and generate the entire repertoire of blood and immune cells throughout an animal's life[1]. Although there have been comprehensive studies on self-renewal, differentiation, physiological regulation and niche occupation in vertebrate HSCs, relatively little is known about the evolutionary origin and niches of these cells. Here we describe the haematopoietic system of Botryllus schlosseri, a colonial tunicate that has a vasculature and circulating blood cells, and interesting stem-cell biology and immunity characteristics[2-8]. Self-recognition between genetically compatible B. schlosseri colonies leads to the formation of natural parabionts with shared circulation, whereas incompatible colonies reject each other[3,4,7]. Using flow cytometry, whole-transcriptome sequencing of defined cell populations and diverse functional assays, we identify HSCs, progenitors, immune effector cells and an HSC niche, and demonstrate that self-recognition inhibits allospecific cytotoxic reactions. Our results show that HSC and myeloid lineage immune cells emerged in a common ancestor of tunicates and vertebrates, and also suggest that haematopoietic bone marrow and the B. schlosseri endostyle niche evolved from a common origin.}, } @article {pmid30510177, year = {2018}, author = {Kayser, J and Schreck, CF and Gralka, M and Fusco, D and Hallatschek, O}, title = {Collective motion conceals fitness differences in crowded cellular populations.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {125-134}, pmid = {30510177}, issn = {2397-334X}, support = {R01 GM115851/GM/NIGMS NIH HHS/United States ; }, mesh = {Biofilms/*growth & development ; *Biological Evolution ; Biomechanical Phenomena ; Humans ; *Microbiota/genetics ; *Models, Biological ; Mutation ; Saccharomyces cerevisiae/genetics/*growth & development ; }, abstract = {Many cellular populations are tightly packed, such as microbial colonies and biofilms, or tissues and tumours in multicellular organisms. The movement of one cell in these crowded assemblages requires motion of others, so that cell displacements are correlated over many cell diameters. Whenever movement is important for survival or growth, these correlated rearrangements could couple the evolutionary fate of different lineages. However, little is known about the interplay between mechanical forces and evolution in dense cellular populations. Here, by tracking slower-growing clones at the expanding edge of yeast colonies, we show that the collective motion of cells prevents costly mutations from being weeded out rapidly. Joint pushing by neighbouring cells generates correlated movements that suppress the differential displacements required for selection to act. This mechanical screening of fitness differences allows slower-growing mutants to leave more descendants than expected under non-mechanical models, thereby increasing their chance for evolutionary rescue. Our work suggests that, in crowded populations, cells cooperate with surrounding neighbours through inevitable mechanical interactions. This effect has to be considered when predicting evolutionary outcomes, such as the emergence of drug resistance or cancer evolution.}, } @article {pmid30500812, year = {2018}, author = {Medina-Castellanos, E and Villalobos-Escobedo, JM and Riquelme, M and Read, ND and Abreu-Goodger, C and Herrera-Estrella, A}, title = {Danger signals activate a putative innate immune system during regeneration in a filamentous fungus.}, journal = {PLoS genetics}, volume = {14}, number = {11}, pages = {e1007390}, pmid = {30500812}, issn = {1553-7404}, mesh = {Adenosine Triphosphate/metabolism ; Animals ; Biomarkers ; Calcium/metabolism ; Gene Expression Regulation, Fungal ; *Host-Pathogen Interactions ; Hyphae ; *Immunity, Innate ; Mycoses/immunology/*microbiology ; *Regeneration ; *Signal Transduction ; Trichoderma/*physiology ; }, abstract = {The ability to respond to injury is a biological process shared by organisms of different kingdoms that can even result in complete regeneration of a part or structure that was lost. Due to their immobility, multicellular fungi are prey to various predators and are therefore constantly exposed to mechanical damage. Nevertheless, our current knowledge of how fungi respond to injury is scarce. Here we show that activation of injury responses and hyphal regeneration in the filamentous fungus Trichoderma atroviride relies on the detection of two danger or alarm signals. As an early response to injury, we detected a transient increase in cytosolic free calcium ([Ca2+]c) that was promoted by extracellular ATP, and which is likely regulated by a mechanism of calcium-induced calcium-release. In addition, we demonstrate that the mitogen activated protein kinase Tmk1 plays a key role in hyphal regeneration. Calcium- and Tmk1-mediated signaling cascades activated major transcriptional changes early following injury, including induction of a set of regeneration associated genes related to cell signaling, stress responses, transcription regulation, ribosome biogenesis/translation, replication and DNA repair. Interestingly, we uncovered the activation of a putative fungal innate immune response, including the involvement of HET domain genes, known to participate in programmed cell death. Our work shows that fungi and animals share danger-signals, signaling cascades, and the activation of the expression of genes related to immunity after injury, which are likely the result of convergent evolution.}, } @article {pmid30498215, year = {2018}, author = {Billerbeck, S and Brisbois, J and Agmon, N and Jimenez, M and Temple, J and Shen, M and Boeke, JD and Cornish, VW}, title = {A scalable peptide-GPCR language for engineering multicellular communication.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {5057}, pmid = {30498215}, issn = {2041-1723}, support = {R01 AI110794/AI/NIAID NIH HHS/United States ; S10 RR027050/RR/NCRR NIH HHS/United States ; T32 GM007308/GM/NIGMS NIH HHS/United States ; T32 GM066704/GM/NIGMS NIH HHS/United States ; }, mesh = {Computational Biology/methods ; Peptides/genetics/*metabolism ; Protein Binding ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Signal Transduction ; Synthetic Biology/methods ; }, abstract = {Engineering multicellularity is one of the next breakthroughs for Synthetic Biology. A key bottleneck to building multicellular systems is the lack of a scalable signaling language with a large number of interfaces that can be used simultaneously. Here, we present a modular, scalable, intercellular signaling language in yeast based on fungal mating peptide/G-protein-coupled receptor (GPCR) pairs harnessed from nature. First, through genome-mining, we assemble 32 functional peptide-GPCR signaling interfaces with a range of dose-response characteristics. Next, we demonstrate that these interfaces can be combined into two-cell communication links, which serve as assembly units for higher-order communication topologies. Finally, we show 56 functional, two-cell links, which we use to assemble three- to six-member communication topologies and a three-member interdependent community. Importantly, our peptide-GPCR language is scalable and tunable by genetic encoding, requires minimal component engineering, and should be massively scalable by further application of our genome mining pipeline or directed evolution.}, } @article {pmid30484227, year = {2018}, author = {Trosko, JE}, title = {The Role of the Mitochondria in the Evolution of Stem Cells, Including MUSE Stem Cells and Their Biology.}, journal = {Advances in experimental medicine and biology}, volume = {1103}, number = {}, pages = {131-152}, doi = {10.1007/978-4-431-56847-6_7}, pmid = {30484227}, issn = {0065-2598}, mesh = {Adult Stem Cells/cytology ; *Biological Evolution ; Cell Differentiation ; Humans ; Induced Pluripotent Stem Cells/cytology ; Mitochondria/*physiology ; Pluripotent Stem Cells/*cytology ; }, abstract = {From the transition of single-cell organisms to multicellularity of metazoans, evolutionary pressures selected new genes and phenotypes to cope with the oxygenation of the Earth's environment, especially via the symbiotic acquisition of the mitochondrial organelle. There were many new genes and phenotypes that appeared, namely, stem cells, low-oxygen-micro-environments to house these genes ("niches"), new epigenetic mechanisms to regulate , selectively, the gene repertoire to control proliferation, differentiation, apoptosis, senescence and DNA protection mechanisms, including antioxidant genes and DNA repair. This transition required a critical regulation of the metabolism of glucose to produce energy for both the stem cell quiescent state and the energy-requiring differentiated state. While the totipotent-, embryonic-, pluripotent-, and a few adult organ-specific stem cells were recognized, only relatively recently, because of the isolation of somatic cell nuclear transfer (SCNT) stem cells and "induced pluripotent stem" cells, challenges to the origin of these "iPS" cells have been made. The isolation and characterization of human MUSE stem cells and more adult organ-specific adult stem cells have indicated that these MUSE cells have many shared characteristics of the "iPS" cells, yet they do not form teratomas but can give rise to the trigeminal cell layers. While the MUSE cells are a subset of human fibroblastic cells, they have not been characterized, yet, for the mitochondrial metabolic genes, either in the stem cell state or during their differentiation processes. A description of other human adult stem cells will be made to set future studies of how the MUSE stem cells compare to all other stem cells.}, } @article {pmid30478288, year = {2019}, author = {Pollier, J and Vancaester, E and Kuzhiumparambil, U and Vickers, CE and Vandepoele, K and Goossens, A and Fabris, M}, title = {A widespread alternative squalene epoxidase participates in eukaryote steroid biosynthesis.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {226-233}, doi = {10.1038/s41564-018-0305-5}, pmid = {30478288}, issn = {2058-5276}, mesh = {Biosynthetic Pathways ; Coenzymes ; Diatoms/enzymology/genetics/metabolism ; Eukaryota/classification/*enzymology/genetics/metabolism ; Gene Expression ; Genetic Complementation Test ; Membrane Proteins/chemistry/genetics/metabolism ; Mixed Function Oxygenases/chemistry/*genetics/*metabolism ; Phylogeny ; Protein Conformation ; Saccharomyces cerevisiae/drug effects/enzymology/genetics/metabolism ; Squalene/analogs & derivatives/metabolism ; Squalene Monooxygenase/chemistry/genetics/metabolism ; Steroids/*biosynthesis ; Terbinafine/pharmacology ; }, abstract = {Steroids are essential triterpenoid molecules that are present in all eukaryotes and modulate the fluidity and flexibility of cell membranes. Steroids also serve as signalling molecules that are crucial for growth, development and differentiation of multicellular organisms[1-3]. The steroid biosynthetic pathway is highly conserved and is key in eukaryote evolution[4-7]. The flavoprotein squalene epoxidase (SQE) catalyses the first oxygenation reaction in this pathway and is rate limiting. However, despite its conservation in animals, plants and fungi, several phylogenetically widely distributed eukaryote genomes lack an SQE-encoding gene[7,8]. Here, we discovered and characterized an alternative SQE (AltSQE) belonging to the fatty acid hydroxylase superfamily. AltSQE was identified through screening of a gene library of the diatom Phaeodactylum tricornutum in a SQE-deficient yeast. In accordance with its divergent protein structure and need for cofactors, we found that AltSQE is insensitive to the conventional SQE inhibitor terbinafine. AltSQE is present in many eukaryotic lineages but is mutually exclusive with SQE and shows a patchy distribution within monophyletic clades. Our discovery provides an alternative element for the conserved steroid biosynthesis pathway, raises questions about eukaryote metabolic evolution and opens routes to develop selective SQE inhibitors to control hazardous organisms.}, } @article {pmid30477635, year = {2018}, author = {Nissen, SB and Rønhild, S and Trusina, A and Sneppen, K}, title = {Theoretical tool bridging cell polarities with development of robust morphologies.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {30477635}, issn = {2050-084X}, mesh = {Animals ; Biomechanical Phenomena ; Cell Adhesion ; Cell Polarity ; Cell Proliferation ; Collagen/chemistry ; Computer Simulation ; Drug Combinations ; Eukaryotic Cells/*cytology/physiology ; Gastrulation/*physiology ; Laminin/chemistry ; Machine Learning ; *Models, Biological ; Organoids/cytology/physiology ; Proteoglycans/chemistry ; Sea Urchins/*cytology/physiology ; }, abstract = {Despite continual renewal and damages, a multicellular organism is able to maintain its complex morphology. How is this stability compatible with the complexity and diversity of living forms? Looking for answers at protein level may be limiting as diverging protein sequences can result in similar morphologies. Inspired by the progressive role of apical-basal and planar cell polarity in development, we propose that stability, complexity, and diversity are emergent properties in populations of proliferating polarized cells. We support our hypothesis by a theoretical approach, developed to effectively capture both types of polar cell adhesions. When applied to specific cases of development - gastrulation and the origins of folds and tubes - our theoretical tool suggests experimentally testable predictions pointing to the strength of polar adhesion, restricted directions of cell polarities, and the rate of cell proliferation to be major determinants of morphological diversity and stability.}, } @article {pmid30473004, year = {2018}, author = {Gruenheit, N and Parkinson, K and Brimson, CA and Kuwana, S and Johnson, EJ and Nagayama, K and Llewellyn, J and Salvidge, WM and Stewart, B and Keller, T and van Zon, W and Cotter, SL and Thompson, CRL}, title = {Cell Cycle Heterogeneity Can Generate Robust Cell Type Proportioning.}, journal = {Developmental cell}, volume = {47}, number = {4}, pages = {494-508.e4}, pmid = {30473004}, issn = {1878-1551}, support = {/WT_/Wellcome Trust/United Kingdom ; BB/M007146/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 105610/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; 095643/A/11/Z/WT_/Wellcome Trust/United Kingdom ; 101582/Z/13/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Cycle/*physiology ; Cell Differentiation/*physiology ; Cell Division/*physiology ; Cell Lineage/physiology ; Dictyostelium/*metabolism ; Spores, Fungal/metabolism ; }, abstract = {Cell-cell heterogeneity can facilitate lineage choice during embryonic development because it primes cells to respond to differentiation cues. However, remarkably little is known about the origin of heterogeneity or whether intrinsic and extrinsic variation can be controlled to generate reproducible cell type proportioning seen in vivo. Here, we use experimentation and modeling in D. discoideum to demonstrate that population-level cell cycle heterogeneity can be optimized to generate robust cell fate proportioning. First, cell cycle position is quantitatively linked to responsiveness to differentiation-inducing signals. Second, intrinsic variation in cell cycle length ensures cells are randomly distributed throughout the cell cycle at the onset of multicellular development. Finally, extrinsic perturbation of optimal cell cycle heterogeneity is buffered by compensatory changes in global signal responsiveness. These studies thus illustrate key regulatory principles underlying cell-cell heterogeneity optimization and the generation of robust and reproducible fate choice in development.}, } @article {pmid30465731, year = {2020}, author = {Beji, O and Adouani, N and Poncin, S and Hamdi, M and Li, HZ}, title = {Mineral pollutants removal through immobilized microalgae-bacterial flocs in a multitrophic microreactor.}, journal = {Environmental technology}, volume = {41}, number = {15}, pages = {1912-1922}, doi = {10.1080/09593330.2018.1551939}, pmid = {30465731}, issn = {1479-487X}, mesh = {Bacteria ; *Environmental Pollutants ; *Microalgae ; Minerals ; Wastewater ; }, abstract = {Microalgae-bacterial flocs (MaB-flocs) immobilization technique using polyvinyl alcohol (PVA) crosslinked with sodium alginate represent a novel approach for sustainable pollutants removal. The present work was performed to evaluate the performance of a multitrophic batch reactor at microscale for treating two synthetic wastewater solutions prepared with two different initial Chemical Oxygen Demand (COD): 200 mg.L[-1] and 450 mg.L[-1], respectively. Three MaB-flocs concentrations were entrapped into PVA-alginate beads: C1 (2%, v/v), C2 (5%, v/v) and C3 (10%, v/v), without O2 supply, during three periods 2, 4 and 6 days of batch incubation. PVA-alginate beads containing the highest concentration C3 of MaB-flocs improved the performance of the microreactor to remove significantly NH4[+] and PO4[3-] of about 61% and 82%, respectively, from wastewater more than two other concentrations used. This result confirms that C3 of MaB-flocs displays not only a good potential for nutrients removals but also the highest MaB-flocs morphological progression after 6 days of treatment with the highest COD of 450 mg.L[-1]. The feasibility of the PVA-alginate for cells immobilization, investigated through microscopy analysis, reveals that the evolution of multicellularity in MaB-flocs, for all experiments.}, } @article {pmid30458131, year = {2018}, author = {Titus, MA and Goodson, HV}, title = {Developing Evolutionary Cell Biology.}, journal = {Developmental cell}, volume = {47}, number = {4}, pages = {395-396}, doi = {10.1016/j.devcel.2018.11.006}, pmid = {30458131}, issn = {1878-1551}, mesh = {Animals ; Biological Evolution ; *Choanoflagellata ; *Phylogeny ; Septins ; Transfection ; }, abstract = {Recent advances in both phylogenetic comparisons and the development of experimentally tractable organisms, in the growing field of evolutionary cell biology, pave the way for gaining a molecular understanding of the development of multicellularity in the animal lineage.}, } @article {pmid30445510, year = {2019}, author = {Saxena, AS and Salomon, MP and Matsuba, C and Yeh, SD and Baer, CF}, title = {Evolution of the Mutational Process under Relaxed Selection in Caenorhabditis elegans.}, journal = {Molecular biology and evolution}, volume = {36}, number = {2}, pages = {239-251}, pmid = {30445510}, issn = {1537-1719}, support = {R01 GM072639/GM/NIGMS NIH HHS/United States ; R01 GM107227/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Caenorhabditis elegans/*genetics ; DNA Copy Number Variations ; Genetic Fitness ; *Genetic Load ; Microsatellite Repeats ; *Mutation ; Recombination, Genetic ; Selection, Genetic ; }, abstract = {The mutational process varies at many levels, from within genomes to among taxa. Many mechanisms have been linked to variation in mutation, but understanding of the evolution of the mutational process is rudimentary. Physiological condition is often implicated as a source of variation in microbial mutation rate and may contribute to mutation rate variation in multicellular organisms.Deleterious mutations are an ubiquitous source of variation in condition. We test the hypothesis that the mutational process depends on the underlying mutation load in two groups of Caenorhabditis elegans mutation accumulation (MA) lines that differ in their starting mutation loads. "First-order MA" (O1MA) lines maintained under minimal selection for ∼250 generations were divided into high-fitness and low-fitness groups and sets of "second-order MA" (O2MA) lines derived from each O1MA line were maintained for ∼150 additional generations. Genomes of 48 O2MA lines and their progenitors were sequenced. There is significant variation among O2MA lines in base-substitution rate (µbs), but no effect of initial fitness; the indel rate is greater in high-fitness O2MA lines. Overall, µbs is positively correlated with recombination and proximity to short tandem repeats and negatively correlated with 10 bp and 1 kb GC content. However, probability of mutation is sufficiently predicted by the three-nucleotide motif alone. Approximately 90% of the variance in standing nucleotide variation is explained by mutability. Total mutation rate increased in the O2MA lines, as predicted by the "drift barrier" model of mutation rate evolution. These data, combined with experimental estimates of fitness, suggest that epistasis is synergistic.}, } @article {pmid30444659, year = {2018}, author = {Rebolleda-Gómez, M and Travisano, M}, title = {The Cost of Being Big: Local Competition, Importance of Dispersal, and Experimental Evolution of Reversal to Unicellularity.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {731-744}, doi = {10.1086/700095}, pmid = {30444659}, issn = {1537-5323}, mesh = {*Biological Evolution ; Computer Simulation ; Saccharomyces cerevisiae/cytology/genetics/*growth & development ; }, abstract = {Multicellularity provides multiple benefits. Nonetheless, unicellularity is ubiquitous, and there have been multiple cases of evolutionary reversal to a unicellular organization. In this article, we explore some of the costs of multicellularity as well as the possibility and dynamics of evolutionary reversals to unicellularity. We hypothesize that recently evolved multicellular organisms would face a high cost of increased competition for local resources in spatially structured environments because of larger size and increased cell densities. To test this hypothesis we conducted competition assays, computer simulations, and selection experiments using isolates of Saccharomyces cerevisiae that recently evolved multicellularity. In well-mixed environments, multicellular isolates had lower growth rates relative to their unicellular ancestor because of limitations of space and resource acquisition. In structured environments with localized resources, cells in both multicellular and unicellular isolates grew at a similar rate. Despite similar growth, higher local density of cells in multicellular groups led to increased competition and higher fitness costs in spatially structured environments. In structured environments all of the multicellular isolates rapidly evolved a predominantly unicellular life cycle, while in well-mixed environments reversal was more gradual. Taken together, these results suggest that a lack of dispersal, leading to higher local competition, might have been one of the main constraints in the evolution of early multicellular forms.}, } @article {pmid30429351, year = {2019}, author = {Ayoubian, H and Ludwig, N and Fehlmann, T and Menegatti, J and Gröger, L and Anastasiadou, E and Trivedi, P and Keller, A and Meese, E and Grässer, FA}, title = {Epstein-Barr Virus Infection of Cell Lines Derived from Diffuse Large B-Cell Lymphomas Alters MicroRNA Loading of the Ago2 Complex.}, journal = {Journal of virology}, volume = {93}, number = {3}, pages = {}, pmid = {30429351}, issn = {1098-5514}, mesh = {Argonaute Proteins/genetics/*metabolism ; Epstein-Barr Virus Infections/*genetics/metabolism/virology ; *Gene Expression Regulation, Neoplastic ; Herpesvirus 4, Human/*isolation & purification ; High-Throughput Nucleotide Sequencing ; Humans ; Lymphoma, Large B-Cell, Diffuse/*genetics/metabolism/virology ; MicroRNAs/*genetics ; Tumor Cells, Cultured ; }, abstract = {Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoid tumor which is occasionally Epstein-Barr virus (EBV) positive and is further subtyped as activated B-cell DLBCL (ABC-DLBCL) and germinal center B-cell DLBCL (GCB-DLBCL), which has implications for prognosis and treatment. We performed Ago2 RNA immunoprecipitation followed by high-throughput RNA sequencing (Ago2-RIP-seq) to capture functionally active microRNAs (miRNAs) in EBV-negative ABC-DLBCL and GCB-DLBCL cell lines and their EBV-infected counterparts. In parallel, total miRNA profiles of these cells were determined to capture the cellular miRNA profile for comparison with the functionally active profile. Selected miRNAs with differential abundances were validated using real-time quantitative PCR (RT-qPCR) and Northern blotting. We found 6 miRNAs with differential abundances (2 upregulated and 4 downregulated miRNAs) between EBV-negative and -positive ABC-DLBCL cells and 12 miRNAs with differential abundances (3 upregulated and 9 downregulated miRNAs) between EBV-negative and -positive GCB-DLBCL cells. Eight and twelve miRNAs were confirmed using RT-qPCR in ABC-DLBCL and GCB-DLBCL cells, respectively. Selected miRNAs were analyzed in additional type I/II versus type III EBV latency DLBCL cell lines. Furthermore, upregulation of miR-221-3p and downregulation of let7c-5p in ABC-DLBCL cells and upregulation of miR-363-3p and downregulation of miR-423-5p in GCB-DLBCL cells were verified using RIP-Northern blotting. Our comprehensive sequence analysis of the DLBCL miRNA profiles identified sets of deregulated miRNAs by Ago2-RIP-seq. Our Ago2-IP-seq miRNA profile could be considered an important data set for the detection of deregulated functionally active miRNAs in DLBCLs and could possibly lead to the identification of miRNAs as biomarkers for the classification of DLBCLs or even as targets for personalized targeted treatment.IMPORTANCE Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive tumor of lymphoid origin which is occasionally Epstein-Barr virus (EBV) positive. MicroRNAs are found in most multicellular organisms and even in viruses such as EBV. They regulate the synthesis of proteins by binding to their cognate mRNA. MicroRNAs are tethered to their target mRNAs by "Argonaute" proteins. Here we compared the overall miRNA content of the Ago2 complex by differential loading to the overall content of miRNAs in two DLBCL cell lines and their EBV-converted counterparts. In all cell lines, the Ago2 load was different from the overall expression of miRNAs. In addition, the loading of the Ago2 complex was changed upon infection with EBV. This indicates that the virus not only changes the overall content of miRNAs but also influences the expression of proteins by affecting the Ago complexes.}, } @article {pmid30427935, year = {2018}, author = {Schneider, P and Greischar, MA and Birget, PLG and Repton, C and Mideo, N and Reece, SE}, title = {Adaptive plasticity in the gametocyte conversion rate of malaria parasites.}, journal = {PLoS pathogens}, volume = {14}, number = {11}, pages = {e1007371}, pmid = {30427935}, issn = {1553-7374}, support = {NE/K006029/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 202769/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {Adaptation, Biological/physiology ; Adaptation, Physiological/*physiology ; Animals ; Biological Evolution ; Computer Simulation ; Erythrocytes/parasitology ; Host-Parasite Interactions ; Malaria/*parasitology ; Models, Theoretical ; Parasites ; Plasmodium/*physiology ; Plasmodium chabaudi/physiology ; Reproduction/physiology ; Reproduction, Asexual/physiology ; }, abstract = {Sexually reproducing parasites, such as malaria parasites, experience a trade-off between the allocation of resources to asexual replication and the production of sexual forms. Allocation by malaria parasites to sexual forms (the conversion rate) is variable but the evolutionary drivers of this plasticity are poorly understood. We use evolutionary theory for life histories to combine a mathematical model and experiments to reveal that parasites adjust conversion rate according to the dynamics of asexual densities in the blood of the host. Our model predicts the direction of change in conversion rates that returns the greatest fitness after perturbation of asexual densities by different doses of antimalarial drugs. The loss of a high proportion of asexuals is predicted to elicit increased conversion (terminal investment), while smaller losses are managed by reducing conversion (reproductive restraint) to facilitate within-host survival and future transmission. This non-linear pattern of allocation is consistent with adaptive reproductive strategies observed in multicellular organisms. We then empirically estimate conversion rates of the rodent malaria parasite Plasmodium chabaudi in response to the killing of asexual stages by different doses of antimalarial drugs and forecast the short-term fitness consequences of these responses. Our data reveal the predicted non-linear pattern, and this is further supported by analyses of previous experiments that perturb asexual stage densities using drugs or within-host competition, across multiple parasite genotypes. Whilst conversion rates, across all datasets, are most strongly influenced by changes in asexual density, parasites also modulate conversion according to the availability of red blood cell resources. In summary, increasing conversion maximises short-term transmission and reducing conversion facilitates in-host survival and thus, future transmission. Understanding patterns of parasite allocation to reproduction matters because within-host replication is responsible for disease symptoms and between-host transmission determines disease spread.}, } @article {pmid30423096, year = {2018}, author = {García-Jiménez, B and García, JL and Nogales, J}, title = {FLYCOP: metabolic modeling-based analysis and engineering microbial communities.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {17}, pages = {i954-i963}, pmid = {30423096}, issn = {1367-4811}, mesh = {Escherichia coli/metabolism ; Metabolic Engineering ; Microbial Consortia ; *Microbiota ; Software ; }, abstract = {MOTIVATION: Synthetic microbial communities begin to be considered as promising multicellular biocatalysts having a large potential to replace engineered single strains in biotechnology applications, in pharmaceutical, chemical and living architecture sectors. In contrast to single strain engineering, the effective and high-throughput analysis and engineering of microbial consortia face the lack of knowledge, tools and well-defined workflows. This manuscript contributes to fill this important gap with a framework, called FLYCOP (FLexible sYnthetic Consortium OPtimization), which contributes to microbial consortia modeling and engineering, while improving the knowledge about how these communities work. FLYCOP selects the best consortium configuration to optimize a given goal, among multiple and diverse configurations, in a flexible way, taking temporal changes in metabolite concentrations into account.

RESULTS: In contrast to previous systems optimizing microbial consortia, FLYCOP has novel characteristics to face up to new problems, to represent additional features and to analyze events influencing the consortia behavior. In this manuscript, FLYCOP optimizes a Synechococcus elongatus-Pseudomonas putida consortium to produce the maximum amount of bio-plastic (PHA, polyhydroxyalkanoate), and highlights the influence of metabolites exchange dynamics in a four auxotrophic Escherichia coli consortium with parallel growth. FLYCOP can also provide an explanation about biological evolution driving evolutionary engineering endeavors by describing why and how heterogeneous populations emerge from monoclonal ones.

Code reproducing the study cases described in this manuscript are available on-line: https://github.com/beatrizgj/FLYCOP.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid30415103, year = {2018}, author = {Schuler, GA and Tice, AK and Pearce, RA and Foreman, E and Stone, J and Gammill, S and Willson, JD and Reading, C and Silberman, JD and Brown, MW}, title = {Phylogeny and Classification of Novel Diversity in Sainouroidea (Cercozoa, Rhizaria) Sheds Light on a Highly Diverse and Divergent Clade.}, journal = {Protist}, volume = {169}, number = {6}, pages = {853-874}, doi = {10.1016/j.protis.2018.08.002}, pmid = {30415103}, issn = {1618-0941}, mesh = {Cercozoa/*classification/cytology/genetics/*isolation & purification ; Cluster Analysis ; DNA, Protozoan/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Environmental Microbiology ; Microscopy ; Microscopy, Electron, Transmission ; *Phylogeny ; RNA, Ribosomal, 18S/genetics ; Sequence Analysis, DNA ; }, abstract = {Sainouroidea is a molecularly diverse clade of cercozoan flagellates and amoebae in the eukaryotic supergroup Rhizaria. Previous 18S rDNA environmental sequencing of globally collected fecal and soil samples revealed great diversity and high sequence divergence in the Sainouroidea. However, a very limited amount of this diversity has been observed or described. The two described genera of amoebae in this clade are Guttulinopsis, which displays aggregative multicellularity, and Rosculus, which does not. Although the identity of Guttulinopsis is straightforward due to the multicellular fruiting bodies they form, the same is not true for Rosculus, and the actual identity of the original isolate is unclear. Here we isolated amoebae with morphologies like that of Guttulinopsis and Rosculus from many environments and analyzed them using 18S rDNA sequencing, light microscopy, and transmission electron microscopy. We define a molecular species concept for Sainouroidea that resulted in the description of 4 novel genera and 12 novel species of naked amoebae. Aggregative fruiting is restricted to the genus Guttulinopsis, but other than this there is little morphological variation amongst these taxa. Taken together, simple identification of these amoebae is problematic and potentially unresolvable without the 18S rDNA sequence.}, } @article {pmid30410727, year = {2018}, author = {Morris, JJ}, title = {What is the hologenome concept of evolution?.}, journal = {F1000Research}, volume = {7}, number = {}, pages = {}, pmid = {30410727}, issn = {2046-1402}, mesh = {Animals ; *Biological Evolution ; Biota ; Genome ; Humans ; Microbiota/*genetics ; Phenotype ; Selection, Genetic ; }, abstract = {All multicellular organisms are colonized by microbes, but a gestalt study of the composition of microbiome communities and their influence on the ecology and evolution of their macroscopic hosts has only recently become possible. One approach to thinking about the topic is to view the host-microbiome ecosystem as a "holobiont". Because natural selection acts on an organism's realized phenotype, and the phenotype of a holobiont is the result of the integrated activities of both the host and all of its microbiome inhabitants, it is reasonable to think that evolution can act at the level of the holobiont and cause changes in the "hologenome", or the collective genomic content of all the individual bionts within the holobiont. This relatively simple assertion has nevertheless been controversial within the microbiome community. Here, I provide a review of recent work on the hologenome concept of evolution. I attempt to provide a clear definition of the concept and its implications and to clarify common points of disagreement.}, } @article {pmid30410109, year = {2018}, author = {Pönisch, W and Eckenrode, KB and Alzurqa, K and Nasrollahi, H and Weber, C and Zaburdaev, V and Biais, N}, title = {Pili mediated intercellular forces shape heterogeneous bacterial microcolonies prior to multicellular differentiation.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {16567}, pmid = {30410109}, issn = {2045-2322}, support = {SC2 AI116566/AI/NIAID NIH HHS/United States ; }, mesh = {Cell Tracking/methods ; Fimbriae, Bacterial/*metabolism ; Microscopy, Electron, Scanning ; Neisseria gonorrhoeae/metabolism/*physiology ; Physical Phenomena ; Single-Cell Analysis ; }, abstract = {Microcolonies are aggregates of a few dozen to a few thousand cells exhibited by many bacteria. The formation of microcolonies is a crucial step towards the formation of more mature bacterial communities known as biofilms, but also marks a significant change in bacterial physiology. Within a microcolony, bacteria forgo a single cell lifestyle for a communal lifestyle hallmarked by high cell density and physical interactions between cells potentially altering their behaviour. It is thus crucial to understand how initially identical single cells start to behave differently while assembling in these tight communities. Here we show that cells in the microcolonies formed by the human pathogen Neisseria gonorrhoeae (Ng) present differential motility behaviors within an hour upon colony formation. Observation of merging microcolonies and tracking of single cells within microcolonies reveal a heterogeneous motility behavior: cells close to the surface of the microcolony exhibit a much higher motility compared to cells towards the center. Numerical simulations of a biophysical model for the microcolonies at the single cell level suggest that the emergence of differential behavior within a multicellular microcolony of otherwise identical cells is of mechanical origin. It could suggest a route toward further bacterial differentiation and ultimately mature biofilms.}, } @article {pmid30404915, year = {2018}, author = {Gao, A and Shrinivas, K and Lepeudry, P and Suzuki, HI and Sharp, PA and Chakraborty, AK}, title = {Evolution of weak cooperative interactions for biological specificity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11053-E11060}, pmid = {30404915}, issn = {1091-6490}, support = {P01 CA042063/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Cell Physiological Phenomena ; *Computer Simulation ; Humans ; *Models, Biological ; Protein Domains/physiology ; Proteins/metabolism ; }, abstract = {A hallmark of biological systems is that particular functions and outcomes are realized in specific contexts, such as when particular signals are received. One mechanism for mediating specificity is described by Fisher's "lock and key" metaphor, exemplified by enzymes that bind selectively to a particular substrate via specific finely tuned interactions. Another mechanism, more prevalent in multicellular organisms, relies on multivalent weak cooperative interactions. Its importance has recently been illustrated by the recognition that liquid-liquid phase transitions underlie the formation of membraneless condensates that perform specific cellular functions. Based on computer simulations of an evolutionary model, we report that the latter mechanism likely became evolutionarily prominent when a large number of tasks had to be performed specifically for organisms to function properly. We find that the emergence of weak cooperative interactions for mediating specificity results in organisms that can evolve to accomplish new tasks with fewer, and likely less lethal, mutations. We argue that this makes the system more capable of undergoing evolutionary changes robustly, and thus this mechanism has been repeatedly positively selected in increasingly complex organisms. Specificity mediated by weak cooperative interactions results in some useful cross-reactivity for related tasks, but at the same time increases susceptibility to misregulation that might lead to pathologies.}, } @article {pmid30404807, year = {2019}, author = {Palmer, WH and Joosten, J and Overheul, GJ and Jansen, PW and Vermeulen, M and Obbard, DJ and Van Rij, RP}, title = {Induction and Suppression of NF-κB Signalling by a DNA Virus of Drosophila.}, journal = {Journal of virology}, volume = {93}, number = {3}, pages = {}, pmid = {30404807}, issn = {1098-5514}, mesh = {Animals ; DNA Viruses/*immunology ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/growth & development/*metabolism/virology ; Female ; Immunity, Innate/*immunology ; NF-kappa B/antagonists & inhibitors/genetics/*metabolism ; RNA Interference ; Signal Transduction ; Toll-Like Receptors/genetics/metabolism ; Viral Proteins/genetics/*metabolism ; Virus Replication/*immunology ; }, abstract = {Interactions between the insect immune system and RNA viruses have been extensively studied in Drosophila, in which RNA interference, NF-κB, and JAK-STAT pathways underlie antiviral immunity. In response to RNA interference, insect viruses have convergently evolved suppressors of this pathway that act by diverse mechanisms to permit viral replication. However, interactions between the insect immune system and DNA viruses have received less attention, primarily because few Drosophila-infecting DNA virus isolates are available. In this study, we used a recently isolated DNA virus of Drosophila melanogaster, Kallithea virus (KV; family Nudiviridae), to probe known antiviral immune responses and virus evasion tactics in the context of DNA virus infection. We found that fly mutants for RNA interference and immune deficiency (Imd), but not Toll, pathways are more susceptible to Kallithea virus infection. We identified the Kallithea virus-encoded protein gp83 as a potent inhibitor of Toll signalling, suggesting that Toll mediates antiviral defense against Kallithea virus infection but that it is suppressed by the virus. We found that Kallithea virus gp83 inhibits Toll signalling through the regulation of NF-κB transcription factors. Furthermore, we found that gp83 of the closely related Drosophila innubila nudivirus (DiNV) suppresses D. melanogaster Toll signalling, suggesting an evolutionarily conserved function of Toll in defense against DNA viruses. Together, these results provide a broad description of known antiviral pathways in the context of DNA virus infection and identify the first Toll pathway inhibitor in a Drosophila virus, extending the known diversity of insect virus-encoded immune inhibitors.IMPORTANCE Coevolution of multicellular organisms and their natural viruses may lead to an intricate relationship in which host survival requires effective immunity and virus survival depends on evasion of such responses. Insect antiviral immunity and reciprocal virus immunosuppression tactics have been well studied in Drosophila melanogaster, primarily during RNA, but not DNA, virus infection. Therefore, we describe interactions between a recently isolated Drosophila DNA virus (Kallithea virus [KV]) and immune processes known to control RNA viruses, such as RNA interference (RNAi) and Imd pathways. We found that KV suppresses the Toll pathway and identified gp83 as a KV-encoded protein that underlies this suppression. This immunosuppressive ability is conserved in another nudivirus, suggesting that the Toll pathway has conserved antiviral activity against DNA nudiviruses, which have evolved suppressors in response. Together, these results indicate that DNA viruses induce and suppress NF-κB responses, and they advance the application of KV as a model to study insect immunity.}, } @article {pmid30396330, year = {2018}, author = {Joo, S and Wang, MH and Lui, G and Lee, J and Barnas, A and Kim, E and Sudek, S and Worden, AZ and Lee, JH}, title = {Common ancestry of heterodimerizing TALE homeobox transcription factors across Metazoa and Archaeplastida.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {136}, pmid = {30396330}, issn = {1741-7007}, mesh = {Animals ; Computational Biology ; *Dimerization ; *Evolution, Molecular ; *Genes, Homeobox ; Phylogeny ; Plants/*genetics ; Transcription Factors/chemistry/*genetics ; }, abstract = {BACKGROUND: Complex multicellularity requires elaborate developmental mechanisms, often based on the versatility of heterodimeric transcription factor (TF) interactions. Homeobox TFs in the TALE superclass are deeply embedded in the gene regulatory networks that orchestrate embryogenesis. Knotted-like homeobox (KNOX) TFs, homologous to animal MEIS, have been found to drive the haploid-to-diploid transition in both unicellular green algae and land plants via heterodimerization with other TALE superclass TFs, demonstrating remarkable functional conservation of a developmental TF across lineages that diverged one billion years ago. Here, we sought to delineate whether TALE-TALE heterodimerization is ancestral to eukaryotes.

RESULTS: We analyzed TALE endowment in the algal radiations of Archaeplastida, ancestral to land plants. Homeodomain phylogeny and bioinformatics analysis partitioned TALEs into two broad groups, KNOX and non-KNOX. Each group shares previously defined heterodimerization domains, plant KNOX-homology in the KNOX group and animal PBC-homology in the non-KNOX group, indicating their deep ancestry. Protein-protein interaction experiments showed that the TALEs in the two groups all participated in heterodimerization.

CONCLUSIONS: Our study indicates that the TF dyads consisting of KNOX/MEIS and PBC-containing TALEs must have evolved early in eukaryotic evolution. Based on our results, we hypothesize that in early eukaryotes, the TALE heterodimeric configuration provided transcription-on switches via dimerization-dependent subcellular localization, ensuring execution of the haploid-to-diploid transition only when the gamete fusion is correctly executed between appropriate partner gametes. The TALE switch then diversified in the several lineages that engage in a complex multicellular organization.}, } @article {pmid30395805, year = {2020}, author = {Ten Tusscher, K}, title = {Of mice and plants: Comparative developmental systems biology.}, journal = {Developmental biology}, volume = {460}, number = {1}, pages = {32-39}, doi = {10.1016/j.ydbio.2018.10.024}, pmid = {30395805}, issn = {1095-564X}, mesh = {Animals ; Body Patterning/*physiology ; Developmental Biology ; Embryonic Development/*physiology ; Gene Expression Regulation, Developmental/*genetics ; Mice ; Models, Biological ; Plant Shoots/*embryology ; Plants ; Signal Transduction/*physiology ; Systems Biology ; }, abstract = {Multicellular animals and plants represent independent evolutionary experiments with complex multicellular bodyplans. Differences in their life history, a mobile versus sessile lifestyle, and predominant embryonic versus postembryonic development, have led to the evolution of highly different body plans. However, also many intriguing parallels exist. Extension of the vertebrate body axis and its segmentation into somites bears striking resemblance to plant root growth and the concomittant prepatterning of lateral root competent sites. Likewise, plant shoot phyllotaxis displays similarities with vertebrate limb and digit patterning. Additionally, both plants and animals use complex signalling systems combining systemic and local signals to fine tune and coordinate organ growth across their body. Identification of these striking examples of convergent evolution provides support for the existence of general design principles: the idea that for particular patterning demands, evolution is likely to arrive at highly similar developmental patterning mechanisms. Furthermore, focussing on these parallels may aid in identifying core mechanistic principles, often obscured by the highly complex nature of multiscale patterning processes.}, } @article {pmid30389796, year = {2019}, author = {Bull, JK and Flynn, JM and Chain, FJJ and Cristescu, ME}, title = {Fitness and Genomic Consequences of Chronic Exposure to Low Levels of Copper and Nickel in Daphnia pulex Mutation Accumulation Lines.}, journal = {G3 (Bethesda, Md.)}, volume = {9}, number = {1}, pages = {61-71}, pmid = {30389796}, issn = {2160-1836}, mesh = {Animals ; Copper/toxicity ; Daphnia/drug effects/*genetics ; Genetic Fitness/drug effects/*genetics ; Genome/*drug effects ; Mutation/drug effects ; Mutation Accumulation ; Mutation Rate ; Nickel/toxicity ; Reproduction/*drug effects/genetics ; Sequence Deletion/drug effects ; }, abstract = {In at least some unicellular organisms, mutation rates are temporarily raised upon exposure to environmental stress, potentially contributing to the evolutionary response to stress. Whether this is true for multicellular organisms, however, has received little attention. This study investigated the effects of chronic mild stress, in the form of low-level copper and nickel exposure, on mutational processes in Daphnia pulex using a combination of mutation accumulation, whole genome sequencing and life-history assays. After over 100 generations of mutation accumulation, we found no effects of metal exposure on the rates of single nucleotide mutations and of loss of heterozygosity events, the two mutation classes that occurred in sufficient numbers to allow statistical analysis. Similarly, rates of decline in fitness, as measured by intrinsic rate of population increase and of body size at first reproduction, were negligibly affected by metal exposure. We can reject the possibility that Daphnia were insufficiently stressed to invoke genetic responses as we have previously shown rates of large-scale deletions and duplications are elevated under metal exposure in this experiment. Overall, the mutation accumulation lines did not significantly depart from initial values for phenotypic traits measured, indicating the lineage used was broadly mutationally robust. Taken together, these results indicate that the mutagenic effects of chronic low-level exposure to these metals are restricted to certain mutation classes and that fitness consequences are likely minor and therefore unlikely to be relevant in determining the evolutionary responses of populations exposed to these stressors.}, } @article {pmid30386324, year = {2018}, author = {Yap, GS and Gause, WC}, title = {Helminth Infections Induce Tissue Tolerance Mitigating Immunopathology but Enhancing Microbial Pathogen Susceptibility.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2135}, pmid = {30386324}, issn = {1664-3224}, support = {R01 AI131634/AI/NIAID NIH HHS/United States ; R01 AI134040/AI/NIAID NIH HHS/United States ; R01 DK113790/DK/NIDDK NIH HHS/United States ; R56 AI124691/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacterial Infections/*immunology/pathology ; Disease Susceptibility ; Helminthiasis/*immunology/pathology ; Host-Parasite Interactions/*immunology ; Humans ; *Lymphocyte Activation ; Protozoan Infections/*immunology/pathology ; T-Lymphocytes/*immunology/pathology ; Virus Diseases/*immunology/pathology ; }, abstract = {Helminths are ubiquitous and have chronically infected vertebrates throughout their evolution. As such helminths have likely exerted considerable selection pressure on our immune systems. The large size of multicellular helminths and their limited replicative capacity in the host necessarily elicits different host protective mechanisms than the immune response evoked by microbial pathogens such as bacteria, viruses and intracellular parasites. The cellular damage resulting from helminth migration through tissues is a major trigger of the type 2 and regulatory immune responses, which activates wound repair mechanisms that increases tissue tolerance to injury and resistance mechanisms that enhance resistance to further colonization with larval stages. While these wound healing and anti-inflammatory responses may be beneficial to the helminth infected host, they may also compromise the host's ability to mount protective immune responses to microbial pathogens. In this review we will first describe helminth-induced tolerance mechanisms that develop in specific organs including the lung and the intestine, and how adaptive immunity may contribute to these responses through differential activation of T cells in the secondary lymphoid organs. We will then integrate studies that have examined how the immune response is modulated in these specific tissues during coinfection of helminths with viruses, protozoa, and bacteria.}, } @article {pmid30377252, year = {2019}, author = {Darris, C and Revert, F and Revert-Ros, F and Gozalbo-Rovira, R and Feigley, A and Fidler, A and Lopez-Pascual, E and Saus, J and Hudson, BG}, title = {Unicellular ancestry and mechanisms of diversification of Goodpasture antigen-binding protein.}, journal = {The Journal of biological chemistry}, volume = {294}, number = {3}, pages = {759-769}, pmid = {30377252}, issn = {1083-351X}, support = {R01 DK018381/DK/NIDDK NIH HHS/United States ; R25 DK096999/DK/NIDDK NIH HHS/United States ; }, mesh = {Basement Membrane/metabolism ; *Evolution, Molecular ; Humans ; Isoenzymes/genetics/metabolism ; Protein Serine-Threonine Kinases/genetics/*metabolism ; }, abstract = {The emergence of the basement membrane (BM), a specialized form of extracellular matrix, was essential in the unicellular transition to multicellularity. However, the mechanism is unknown. Goodpasture antigen-binding protein (GPBP), a BM protein, was uniquely poised to play diverse roles in this transition owing to its multiple isoforms (GPBP-1, -2, and -3) with varied intracellular and extracellular functions (ceramide trafficker and protein kinase). We sought to determine the evolutionary origin of GPBP isoforms. Our findings reveal the presence of GPBP in unicellular protists, with GPBP-2 as the most ancient isoform. In vertebrates, GPBP-1 assumed extracellular function that is further enhanced by membrane-bound GPBP-3 in mammalians, whereas GPBP-2 retained intracellular function. Moreover, GPBP-2 possesses a dual intracellular/extracellular function in cnidarians, an early nonbilaterian group. We conclude that GPBP functioning both inside and outside the cell was of fundamental importance for the evolutionary transition to animal multicellularity and tissue evolution.}, } @article {pmid30368592, year = {2019}, author = {Niklas, KJ and Wayne, R and Benítez, M and Newman, SA}, title = {Polarity, planes of cell division, and the evolution of plant multicellularity.}, journal = {Protoplasma}, volume = {256}, number = {3}, pages = {585-599}, pmid = {30368592}, issn = {1615-6102}, mesh = {*Biological Evolution ; *Cell Division ; *Cell Polarity ; Meristem/cytology ; Phylogeny ; Plant Cells/*metabolism ; }, abstract = {Organisms as diverse as bacteria, fungi, plants, and animals manifest a property called "polarity." The literature shows that polarity emerges as a consequence of different mechanisms in different lineages. However, across all unicellular and multicellular organisms, polarity is evident when cells, organs, or organisms manifest one or more of the following: orientation, axiation, and asymmetry. Here, we review the relationships among these three features in the context of cell division and the evolution of multicellular polarity primarily in plants (defined here to include the algae). Data from unicellular and unbranched filamentous organisms (e.g., Chlamydomonas and Ulothrix) show that cell orientation and axiation are marked by cytoplasmic asymmetries. Branched filamentous organisms (e.g., Cladophora and moss protonema) require an orthogonal reorientation of axiation, or a localized cell asymmetry (e.g., "tip" growth in pollen tubes and fungal hyphae). The evolution of complex multicellular meristematic polarity required a third reorientation of axiation. These transitions show that polarity and the orientation of the future plane(s) of cell division are dyadic dynamical patterning modules that were critical for multicellular eukaryotic organisms.}, } @article {pmid30362942, year = {2018}, author = {Castiglione, GM and Chang, BS}, title = {Functional trade-offs and environmental variation shaped ancient trajectories in the evolution of dim-light vision.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {30362942}, issn = {2050-084X}, support = {Discovery grant//Natural Sciences and Engineering Research Council of Canada/International ; }, mesh = {*Adaptation, Biological ; Animals ; *Biological Evolution ; Epistasis, Genetic ; Light ; Rhodopsin/genetics ; Selection, Genetic ; *Vertebrates ; Vision, Ocular/*physiology ; }, abstract = {Trade-offs between protein stability and activity can restrict access to evolutionary trajectories, but widespread epistasis may facilitate indirect routes to adaptation. This may be enhanced by natural environmental variation, but in multicellular organisms this process is poorly understood. We investigated a paradoxical trajectory taken during the evolution of tetrapod dim-light vision, where in the rod visual pigment rhodopsin, E122 was fixed 350 million years ago, a residue associated with increased active-state (MII) stability but greatly diminished rod photosensitivity. Here, we demonstrate that high MII stability could have likely evolved without E122, but instead, selection appears to have entrenched E122 in tetrapods via epistatic interactions with nearby coevolving sites. In fishes by contrast, selection may have exploited these epistatic effects to explore alternative trajectories, but via indirect routes with low MII stability. Our results suggest that within tetrapods, E122 and high MII stability cannot be sacrificed-not even for improvements to rod photosensitivity.}, } @article {pmid30357728, year = {2018}, author = {Fitzgerald, RS}, title = {O2/CO2: Biological Detection to Homeostatic Control.}, journal = {Advances in experimental medicine and biology}, volume = {1071}, number = {}, pages = {1-12}, doi = {10.1007/978-3-319-91137-3_1}, pmid = {30357728}, issn = {0065-2598}, mesh = {Animals ; Atmosphere ; Carbon Dioxide/*analysis/physiology ; *Homeostasis ; Oxygen/*analysis/physiology ; Photosynthesis ; }, abstract = {Oxygen (O2) and Carbon Dioxide (CO2) are the two gases to be detected and controlled. Of interest might be a query of the evolutionary origin of each. From the cooling of the Big Bang (~13.8 Billion Years Ago [BYA]) came a quark-gluon plasma from which protons and neutrons emerged, producing H, He, Li. As H and He collapsed into the first stars at ~13.3 BYA carbon and monatomic oxygen were generated. Some 3 billion years ago greater amounts of diatomic oxygen (O2) were provided by earth's photosynthesizing bacteria until earth's atmosphere had sufficient amounts to sustain the life processes of multicellular animals, and finally higher vertebrates. Origin of CO2 is somewhat unclear, though it probably came from the erupting early volcanoes. Photosynthesis produced sugars with O2 a waste product. Animal life took sugars and O2 needed for life. Clearly, animal detection and control of each was critical. Many chapters involving great heroes describe phases involved in detecting each, both in the CNS and in peripheral detectors. The carotid body (CB) has played a crucial role in the detection of each. What reflex responses the stimulated CB generates, and the mechanisms as to how it does so have been a fascinating story over the last 1.5 centuries, but principally over the last 50 years. Explorations to detect these gases have proceeded from the organismal/system/ organ levels down to the sub-cell and genetic levels.}, } @article {pmid30350947, year = {2019}, author = {Budin, I and Keasling, JD}, title = {Synthetic Biology for Fundamental Biochemical Discovery.}, journal = {Biochemistry}, volume = {58}, number = {11}, pages = {1464-1469}, doi = {10.1021/acs.biochem.8b00915}, pmid = {30350947}, issn = {1520-4995}, mesh = {Biological Evolution ; Gene Regulatory Networks ; Protein Engineering/methods/*trends ; Research/trends ; Research Design/trends ; Synthetic Biology/*methods/*trends ; }, abstract = {Synthetic biologists have developed sophisticated molecular and genetic tools to engineer new biochemical functions in cells. Applications for these tools have focused on important problems in energy and medicine, but they can also be applied to address basic science topics that cannot be easily accessed by classical approaches. We focus on recent work that has utilized synthetic biology approaches, ranging from promoter engineering to the de novo synthesis of cellular parts, to investigate a wide range of biochemical and cellular questions. Insights obtained by these efforts include how fatty acid composition mediates cellular metabolism, how transcriptional circuits act to stabilize multicellular networks, and fitness trade-offs involved in the selection of genetic regulatory elements. We also highlight common themes about how "discovery by synthesis" approaches can aid fundamental research. For example, rewiring of native metabolism through metabolic engineering is a powerful tool for investigating biological molecules whose exact composition and abundance are key for function. Meanwhile, endeavors to synthesize cells and their components allow scientists to address evolutionary questions that are otherwise constrained by extant laboratory models.}, } @article {pmid30348074, year = {2018}, author = {Kin, K and Forbes, G and Cassidy, A and Schaap, P}, title = {Cell-type specific RNA-Seq reveals novel roles and regulatory programs for terminally differentiated Dictyostelium cells.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {764}, pmid = {30348074}, issn = {1471-2164}, support = {742288//H2020 European Research Council/ ; ALTF 295-2015//European Molecular Biology Organization/ ; H28-1002//Japan Society for the Promotion of Science/ ; }, mesh = {Dictyostelium/*cytology/*genetics/metabolism ; Gene Expression Regulation ; Gene Ontology ; Metabolic Networks and Pathways/genetics ; RNA, Protozoan/*genetics ; *Sequence Analysis, RNA ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: A major hallmark of multicellular evolution is increasing complexity by the evolution of new specialized cell types. During Dictyostelid evolution novel specialization occurred within taxon group 4. We here aim to retrace the nature and ancestry of the novel "cup" cells by comparing their transcriptome to that of other cell types.

RESULTS: RNA-Seq was performed on purified mature spore, stalk and cup cells and on vegetative amoebas. Clustering and phylogenetic analyses showed that cup cells were most similar to stalk cells, suggesting that they share a common ancestor. The affinity between cup and stalk cells was also evident from promoter-reporter studies of newly identified cell-type genes, which revealed late expression in cups of many stalk genes. However, GO enrichment analysis reveal the unexpected prominence of GTPase mediated signalling in cup cells, in contrast to enrichment of autophagy and cell wall synthesis related transcripts in stalk cells. Combining the cell type RNA-Seq data with developmental expression profiles revealed complex expression dynamics in each cell type as well as genes exclusively expressed during terminal differentiation. Most notable were nine related hssA-like genes that were highly and exclusively expressed in cup cells.

CONCLUSIONS: This study reveals the unique transcriptomes of the mature cup, stalk and spore cells of D. discoideum and provides insight into the ancestry of cup cells and roles in signalling that were not previously realized. The data presented in this study will serve as an important resource for future studies into the regulation and evolution of cell type specialization.}, } @article {pmid30339672, year = {2018}, author = {Crombie, TA and Saber, S and Saxena, AS and Egan, R and Baer, CF}, title = {Head-to-head comparison of three experimental methods of quantifying competitive fitness in C. elegans.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0201507}, pmid = {30339672}, issn = {1932-6203}, support = {R01 GM107227/GM/NIGMS NIH HHS/United States ; S10 OD012006/OD/NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Automation ; Biological Evolution ; Caenorhabditis elegans/*genetics/*physiology ; *Genetic Fitness ; Genotype ; Green Fluorescent Proteins/metabolism ; Models, Biological ; Models, Statistical ; Reproducibility of Results ; Software ; }, abstract = {Organismal fitness is relevant in many contexts in biology. The most meaningful experimental measure of fitness is competitive fitness, when two or more entities (e.g., genotypes) are allowed to compete directly. In theory, competitive fitness is simple to measure: an experimental population is initiated with the different types in known proportions and allowed to evolve under experimental conditions to a predefined endpoint. In practice, there are several obstacles to obtaining robust estimates of competitive fitness in multicellular organisms, the most pervasive of which is simply the time it takes to count many individuals of different types from many replicate populations. Methods by which counting can be automated in high throughput are desirable, but for automated methods to be useful, the bias and technical variance associated with the method must be (a) known, and (b) sufficiently small relative to other sources of bias and variance to make the effort worthwhile. The nematode Caenorhabditis elegans is an important model organism, and the fitness effects of genotype and environmental conditions are often of interest. We report a comparison of three experimental methods of quantifying competitive fitness, in which wild-type strains are competed against GFP-marked competitors under standard laboratory conditions. Population samples were split into three replicates and counted (1) "by eye" from a saved image, (2) from the same image using CellProfiler image analysis software, and (3) with a large particle flow cytometer (a "worm sorter"). From 720 replicate samples, neither the frequency of wild-type worms nor the among-sample variance differed significantly between the three methods. CellProfiler and the worm sorter provide at least a tenfold increase in sample handling speed with little (if any) bias or increase in variance.}, } @article {pmid30336184, year = {2019}, author = {Miller, WB and Torday, JS and Baluška, F}, title = {Biological evolution as defense of 'self'.}, journal = {Progress in biophysics and molecular biology}, volume = {142}, number = {}, pages = {54-74}, doi = {10.1016/j.pbiomolbio.2018.10.002}, pmid = {30336184}, issn = {1873-1732}, mesh = {*Biological Evolution ; Cell Physiological Phenomena ; Cells/metabolism ; Cognition/physiology ; Consciousness/*physiology ; Emotions/physiology ; Homeostasis/physiology ; Humans ; Intelligence/physiology ; Signal Transduction ; }, abstract = {Although the origin of self-referential consciousness is unknown, it can be argued that the instantiation of self-reference was the commencement of the living state as phenomenal experientiality. As self-referential cognition is demonstrated by all living organisms, life can be equated with the sustenance of cellular homeostasis in the continuous defense of 'self'. It is proposed that the epicenter of 'self' is perpetually embodied within the basic cellular form in which it was instantiated. Cognition-Based Evolution argues that all of biological and evolutionary development represents the perpetual autopoietic defense of self-referential basal cellular states of homeostatic preference. The means by which these states are attained and maintained is through self-referential measurement of information and its communication. The multicellular forms, either as biofilms or holobionts, represent the cellular attempt to achieve maximum states of informational distinction and energy efficiency through individual and collective means. In this frame, consciousness, self-consciousness and intelligence can be identified as forms of collective cellular phenotype directed towards the defense of fundamental cellular self-reference.}, } @article {pmid30325443, year = {2018}, author = {Skaldin, M and Tuittila, M and Zavialov, AV and Zavialov, AV}, title = {Secreted Bacterial Adenosine Deaminase Is an Evolutionary Precursor of Adenosine Deaminase Growth Factor.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2851-2861}, doi = {10.1093/molbev/msy193}, pmid = {30325443}, issn = {1537-1719}, mesh = {Adenosine Deaminase/*genetics ; Amino Acid Sequence ; Bacterial Proteins/*genetics ; Drosophila Proteins/genetics ; *Evolution, Molecular ; Intercellular Signaling Peptides and Proteins/genetics ; Multigene Family ; Phylogeny ; }, abstract = {Adenosine deaminases (ADAs) play a pivotal role in regulating the level of adenosine, an important signaling molecule that controls a variety of cellular responses. Two distinct ADAs, ADA1 and adenosine deaminase growth factor (ADGF aka ADA2), are known. Cytoplasmic ADA1 plays a key role in purine metabolism and is widely distributed from prokaryotes to mammals. On the other hand, secreted ADGF/ADA2 is a cell-signaling protein that was thought to be present only in multicellular organisms. Here, we discovered a bacterial homologue of ADGF/ADA2. Bacterial and eukaryotic ADGF/ADA2 possess the dimerization and PRB domains characteristic for the family, have nearly identical catalytic sites, and show similar catalytic characteristics. Most surprisingly, the bacterial enzyme has a signal sequence similar to that of eukaryotic ADGF/ADA2 and is specifically secreted into the extracellular space, where it may potentially control the level of extracellular adenosine. This finding provides the first example of evolution of an extracellular eukaryotic signaling protein from a secreted bacterial analogue with identical activity and suggests a potential role of ADGF/ADA2 in bacterial communication.}, } @article {pmid30323207, year = {2018}, author = {Zumberge, JA and Love, GD and Cárdenas, P and Sperling, EA and Gunasekera, S and Rohrssen, M and Grosjean, E and Grotzinger, JP and Summons, RE}, title = {Demosponge steroid biomarker 26-methylstigmastane provides evidence for Neoproterozoic animals.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1709-1714}, pmid = {30323207}, issn = {2397-334X}, support = {80NSSC18K1085//Intramural NASA/United States ; }, mesh = {Animals ; *Biological Evolution ; Biomarkers/*analysis ; *Fossils ; Phylogeny ; Porifera/*chemistry ; Steroids/*analysis ; }, abstract = {Sterane biomarkers preserved in ancient sedimentary rocks hold promise for tracking the diversification and ecological expansion of eukaryotes. The earliest proposed animal biomarkers from demosponges (Demospongiae) are recorded in a sequence around 100 Myr long of Neoproterozoic-Cambrian marine sedimentary strata from the Huqf Supergroup, South Oman Salt Basin. This C30 sterane biomarker, informally known as 24-isopropylcholestane (24-ipc), possesses the same carbon skeleton as sterols found in some modern-day demosponges. However, this evidence is controversial because 24-ipc is not exclusive to demosponges since 24-ipc sterols are found in trace amounts in some pelagophyte algae. Here, we report a new fossil sterane biomarker that co-occurs with 24-ipc in a suite of late Neoproterozoic-Cambrian sedimentary rocks and oils, which possesses a rare hydrocarbon skeleton that is uniquely found within extant demosponge taxa. This sterane is informally designated as 26-methylstigmastane (26-mes), reflecting the very unusual methylation at the terminus of the steroid side chain. It is the first animal-specific sterane marker detected in the geological record that can be unambiguously linked to precursor sterols only reported from extant demosponges. These new findings strongly suggest that demosponges, and hence multicellular animals, were prominent in some late Neoproterozoic marine environments at least extending back to the Cryogenian period.}, } @article {pmid30320194, year = {2018}, author = {Yang, R and Broussard, JA and Green, KJ and Espinosa, HD}, title = {Techniques to stimulate and interrogate cell-cell adhesion mechanics.}, journal = {Extreme Mechanics Letters}, volume = {20}, number = {}, pages = {125-139}, pmid = {30320194}, issn = {2352-4316}, support = {R01 AR041836/AR/NIAMS NIH HHS/United States ; R01 CA122151/CA/NCI NIH HHS/United States ; R37 AR043380/AR/NIAMS NIH HHS/United States ; }, abstract = {Cell-cell adhesions maintain the mechanical integrity of multicellular tissues and have recently been found to act as mechanotransducers, translating mechanical cues into biochemical signals. Mechanotransduction studies have primarily focused on focal adhesions, sites of cell-substrate attachment. These studies leverage technical advances in devices and systems interfacing with living cells through cell-extracellular matrix adhesions. As reports of aberrant signal transduction originating from mutations in cell-cell adhesion molecules are being increasingly associated with disease states, growing attention is being paid to this intercellular signaling hub. Along with this renewed focus, new requirements arise for the interrogation and stimulation of cell-cell adhesive junctions. This review covers established experimental techniques for stimulation and interrogation of cell-cell adhesion from cell pairs to monolayers.}, } @article {pmid30318349, year = {2018}, author = {Bråte, J and Neumann, RS and Fromm, B and Haraldsen, AAB and Tarver, JE and Suga, H and Donoghue, PCJ and Peterson, KJ and Ruiz-Trillo, I and Grini, PE and Shalchian-Tabrizi, K}, title = {Unicellular Origin of the Animal MicroRNA Machinery.}, journal = {Current biology : CB}, volume = {28}, number = {20}, pages = {3288-3295.e5}, pmid = {30318349}, issn = {1879-0445}, mesh = {Animals ; Base Sequence ; *Evolution, Molecular ; Mesomycetozoea/*genetics/metabolism ; MicroRNAs/*genetics/metabolism ; Phylogeny ; }, abstract = {The emergence of multicellular animals was associated with an increase in phenotypic complexity and with the acquisition of spatial cell differentiation and embryonic development. Paradoxically, this phenotypic transition was not paralleled by major changes in the underlying developmental toolkit and regulatory networks. In fact, most of these systems are ancient, established already in the unicellular ancestors of animals [1-5]. In contrast, the Microprocessor protein machinery, which is essential for microRNA (miRNA) biogenesis in animals, as well as the miRNA genes themselves produced by this Microprocessor, have not been identified outside of the animal kingdom [6]. Hence, the Microprocessor, with the key proteins Pasha and Drosha, is regarded as an animal innovation [7-9]. Here, we challenge this evolutionary scenario by investigating unicellular sister lineages of animals through genomic and transcriptomic analyses. We identify in Ichthyosporea both Drosha and Pasha (DGCR8 in vertebrates), indicating that the Microprocessor complex evolved long before the last common ancestor of animals, consistent with a pre-metazoan origin of most of the animal developmental gene elements. Through small RNA sequencing, we also discovered expressed bona fide miRNA genes in several species of the ichthyosporeans harboring the Microprocessor. A deep, pre-metazoan origin of the Microprocessor and miRNAs comply with a view that the origin of multicellular animals was not directly linked to the innovation of these key regulatory components.}, } @article {pmid30309963, year = {2018}, author = {Armon, S and Bull, MS and Aranda-Diaz, A and Prakash, M}, title = {Ultrafast epithelial contractions provide insights into contraction speed limits and tissue integrity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10333-E10341}, pmid = {30309963}, issn = {1091-6490}, mesh = {Actins/metabolism ; Animals ; Aquatic Organisms/metabolism/*physiology ; Cells, Cultured ; Epithelial Cells/metabolism/*physiology ; Epithelium/metabolism/*physiology ; Myosins/metabolism ; Placozoa/metabolism/*physiology ; }, abstract = {By definition of multicellularity, all animals need to keep their cells attached and intact, despite internal and external forces. Cohesion between epithelial cells provides this key feature. To better understand fundamental limits of this cohesion, we study the epithelium mechanics of an ultrathin (∼25 μm) primitive marine animal Trichoplax adhaerens, composed essentially of two flat epithelial layers. With no known extracellular matrix and no nerves or muscles, T. adhaerens has been claimed to be the "simplest known living animal," yet is still capable of coordinated locomotion and behavior. Here we report the discovery of the fastest epithelial cellular contractions known in any metazoan, to be found in T. adhaerens dorsal epithelium (50% shrinkage of apical cell area within one second, at least an order of magnitude faster than other known examples). Live imaging reveals emergent contractile patterns that are mostly sporadic single-cell events, but also include propagating contraction waves across the tissue. We show that cell contraction speed can be explained by current models of nonmuscle actin-myosin bundles without load, while the tissue architecture and unique mechanical properties are softening the tissue, minimizing the load on a contracting cell. We propose a hypothesis, in which the physiological role of the contraction dynamics is to resist external stresses while avoiding tissue rupture ("active cohesion"), a concept that can be further applied to engineering of active materials.}, } @article {pmid30295813, year = {2018}, author = {Sperling, EA and Stockey, RG}, title = {The Temporal and Environmental Context of Early Animal Evolution: Considering All the Ingredients of an "Explosion".}, journal = {Integrative and comparative biology}, volume = {58}, number = {4}, pages = {605-622}, doi = {10.1093/icb/icy088}, pmid = {30295813}, issn = {1557-7023}, mesh = {Animals ; *Biological Evolution ; Fossils/*anatomy & histology ; Invertebrates/*anatomy & histology/classification ; Phylogeny ; }, abstract = {Animals originated and evolved during a unique time in Earth history-the Neoproterozoic Era. This paper aims to discuss (1) when landmark events in early animal evolution occurred, and (2) the environmental context of these evolutionary milestones, and how such factors may have affected ecosystems and body plans. With respect to timing, molecular clock studies-utilizing a diversity of methodologies-agree that animal multicellularity had arisen by ∼800 million years ago (Ma) (Tonian period), the bilaterian body plan by ∼650 Ma (Cryogenian), and divergences between sister phyla occurred ∼560-540 Ma (late Ediacaran). Most purported Tonian and Cryogenian animal body fossils are unlikely to be correctly identified, but independent support for the presence of pre-Ediacaran animals is recorded by organic geochemical biomarkers produced by demosponges. This view of animal origins contrasts with data from the fossil record, and the taphonomic question of why animals were not preserved (if present) remains unresolved. Neoproterozoic environments demanding small, thin, body plans, and lower abundance/rarity in populations may have played a role. Considering environmental conditions, geochemical data suggest that animals evolved in a relatively low-oxygen ocean. Here, we present new analyses of sedimentary total organic carbon contents in shales suggesting that the Neoproterozoic ocean may also have had lower primary productivity-or at least lower quantities of organic carbon reaching the seafloor-compared with the Phanerozoic. Indeed, recent modeling efforts suggest that low primary productivity is an expected corollary of a low-O2 world. Combined with an inability to inhabit productive regions in a low-O2 ocean, earliest animal communities would likely have been more food limited than generally appreciated, impacting both ecosystem structure and organismal behavior. In light of this, we propose the "fire triangle" metaphor for environmental influences on early animal evolution. Moving toward consideration of all environmental aspects of the Cambrian radiation (fuel, heat, and oxidant) will ultimately lead to a more holistic view of the event.}, } @article {pmid30288746, year = {2018}, author = {Stiller, JW and Yang, C and Collén, J and Kowalczyk, N and Thompson, BE}, title = {Evolution and expression of core SWI/SNF genes in red algae.}, journal = {Journal of phycology}, volume = {54}, number = {6}, pages = {879-887}, doi = {10.1111/jpy.12795}, pmid = {30288746}, issn = {1529-8817}, support = {0741907//NSF Research Collaboration Network/International ; DE-AC02-05CH11231//U.S. Department of Energy Joint Genome Institute/International ; }, mesh = {Algal Proteins/*genetics/metabolism ; *Chromatin Assembly and Disassembly ; Genome ; Reverse Transcriptase Polymerase Chain Reaction ; Rhodophyta/*genetics/metabolism ; *Transcription, Genetic ; Transcriptome ; }, abstract = {Red algae are the oldest identifiable multicellular eukaryotes, with a fossil record dating back more than a billion years. During that time two major rhodophyte lineages, bangiophytes and florideophytes, have evolved varied levels of morphological complexity. These two groups are distinguished, in part, by different patterns of multicellular development, with florideophytes exhibiting a far greater diversity of morphologies. Interestingly, during their long evolutionary history, there is no record of a rhodophyte achieving the kinds of cellular and tissue-specific differentiation present in other multicellular algal lineages. To date, the genetic underpinnings of unique aspects of red algal development are largely unexplored; however, they must reflect the complements and patterns of expression of key regulatory genes. Here we report comparative evolutionary and gene expression analyses of core subunits of the SWI/SNF chromatin-remodeling complex, which is implicated in cell differentiation and developmental regulation in more well studied multicellular groups. Our results suggest that a single, canonical SWI/SNF complex was present in the rhodophyte ancestor, with gene duplications and evolutionary diversification of SWI/SNF subunits accompanying the evolution of multicellularity in the common ancestor of bangiophytes and florideophytes. Differences in how SWI/SNF chromatin remodeling evolved subsequently, in particular gene losses and more rapid divergence of SWI3 and SNF5 in bangiophytes, could help to explain why they exhibit a more limited range of morphological complexity than their florideophyte cousins.}, } @article {pmid30283698, year = {2018}, author = {Godwin, JL and Spurgin, LG and Michalczyk, Ł and Martin, OY and Lumley, AJ and Chapman, T and Gage, MJG}, title = {Lineages evolved under stronger sexual selection show superior ability to invade conspecific competitor populations.}, journal = {Evolution letters}, volume = {2}, number = {5}, pages = {511-523}, pmid = {30283698}, issn = {2056-3744}, abstract = {Despite limitations on offspring production, almost all multicellular species use sex to reproduce. Sex gives rise to sexual selection, a widespread force operating through competition and choice within reproduction, however, it remains unclear whether sexual selection is beneficial for total lineage fitness, or if it acts as a constraint. Sexual selection could be a positive force because of selection on improved individual condition and purging of mutation load, summing into lineages with superior fitness. On the other hand, sexual selection could negate potential net fitness through the actions of sexual conflict, or because of tensions between investment in sexually selected and naturally selected traits. Here, we explore these ideas using a multigenerational invasion challenge to measure consequences of sexual selection for the overall net fitness of a lineage. After applying experimental evolution under strong versus weak regimes of sexual selection for 77 generations with the flour beetle Tribolium castaneum, we measured the overall ability of introductions from either regime to invade into conspecific competitor populations across eight generations. Results showed that populations from stronger sexual selection backgrounds had superior net fitness, invading more rapidly and completely than counterparts from weak sexual selection backgrounds. Despite comprising only 10% of each population at the start of the invasion experiment, colonizations from strong sexual selection histories eventually achieved near-total introgression, almost completely eliminating the original competitor genotype. Population genetic simulations using the design and parameters of our experiment indicate that this invasion superiority could be explained if strong sexual selection had improved both juvenile and adult fitness, in both sexes. Using a combination of empirical and modeling approaches, our findings therefore reveal positive and wide-reaching impacts of sexual selection for net population fitness when facing the broad challenge of invading competitor populations across multiple generations.}, } @article {pmid30281390, year = {2018}, author = {Booth, DS and Szmidt-Middleton, H and King, N}, title = {Transfection of choanoflagellates illuminates their cell biology and the ancestry of animal septins.}, journal = {Molecular biology of the cell}, volume = {29}, number = {25}, pages = {3026-3038}, pmid = {30281390}, issn = {1939-4586}, mesh = {Choanoflagellata/*genetics/physiology ; Evolution, Molecular ; Fluorescent Dyes ; Genetic Markers ; Plasmids ; Septins/genetics/*physiology ; Transfection/*methods ; }, abstract = {As the closest living relatives of animals, choanoflagellates offer unique insights into animal origins and core mechanisms underlying animal cell biology. However, unlike traditional model organisms, such as yeast, flies, and worms, choanoflagellates have been refractory to DNA delivery methods for expressing foreign genes. Here we report a robust method for expressing transgenes in the choanoflagellate Salpingoeca rosetta, overcoming barriers that have previously hampered DNA delivery and expression. To demonstrate how this method accelerates the study of S. rosetta cell biology, we engineered a panel of fluorescent protein markers that illuminate key features of choanoflagellate cells. We then investigated the localization of choanoflagellate septins, a family of GTP-binding cytoskeletal proteins that are hypothesized to regulate multicellular rosette development in S. rosetta. Fluorescently tagged septins localized to the basal poles of S. rosetta single cells and rosettes in a pattern resembling septin localization in animal epithelia. The establishment of transfection in S. rosetta and its application to the study of septins represent critical advances in the use of S. rosetta as an experimental model for investigating choanoflagellate cell biology, core mechanisms underlying animal cell biology, and the origin of animals.}, } @article {pmid30280251, year = {2019}, author = {Zhou, W and Gao, B and Zhu, S}, title = {Did cis- and trans-defensins derive from a common ancestor?.}, journal = {Immunogenetics}, volume = {71}, number = {1}, pages = {61-69}, pmid = {30280251}, issn = {1432-1211}, mesh = {Defensins/*chemistry/genetics ; Evolution, Molecular ; Phylogeny ; Protein Folding ; Protein Structure, Secondary ; }, abstract = {Defensins are small, cysteine-rich, cationic antimicrobial peptides, serving as effectors of the innate immune system and modulators of the adaptive immune system. They extensively exist in multicellular organisms and are divided into cis and trans according to their disulfide bridge connectivity patterns. It has been proposed that these two types of defensins convergently originated from different ancestors. Here, we report the discovery of a structural signature involved in the formation of the cysteine-stabilized α-helix/β-sheet (CSαβ) fold of the cis-defensins in some trans-β-defensins, with only one amino acid indel (CXC vs. CC. C, cysteine; X, any amino acid). The indel of the X residue in the structural signature provides a possible explanation as to why cis- and trans-defensins possess different folds and connectivity patterns of disulfide bridges formed in evolution. Although our attempt to convert the structure type of a present-day trans-defensin with the X residue deleted was unsuccessful due to the low solubility of the synthetic peptide, a combination of data from structural signature, function, and phylogenetic distribution suggests that these defensins may have descended from a common ancestor. In this evolutionary scenario, we propose that a progenitor cis-scaffold might gradually evolve into a trans-defensin after deleting the X residue in specific lineages. This proposal adds a new dimension to more deeply studying the evolutionary relationship of defensins with different folds and of other distantly related proteins.}, } @article {pmid30271390, year = {2018}, author = {Teng, Z and Zhang, Y and Zhang, W and Pan, H and Xu, J and Huang, H and Xiao, T and Wu, LF}, title = {Diversity and Characterization of Multicellular Magnetotactic Prokaryotes From Coral Reef Habitats of the Paracel Islands, South China Sea.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2135}, pmid = {30271390}, issn = {1664-302X}, abstract = {While multicellular magnetotactic prokaryotes (MMPs) are ubiquitous in marine environments, the diversity of MMPs in sediments of coral reef ecosystems has rarely been reported. In this study, we made an investigation on the diversity and characteristics of MMPs in sediments at 11 stations in coral reef habitats of the Paracel Islands. The results showed that MMPs were present at nine stations, with spherical mulberry-like MMPs (s-MMPs) found at all stations and ellipsoidal pineapple-like MMPs (e-MMPs) found at seven stations. The maximum abundance of MMPs was 6 ind./cm[3]. Phylogenetic analysis revealed the presence of one e-MMP species and five s-MMP species including two species of a new genus. The results indicate that coral reef habitats of the Paracel Islands have a high diversity of MMPs that bio-mineralize multiple intracellular chains of iron crystals and play important role in iron cycling in such oligotrophic environment. These observations provide new perspective of the diversity of MMPs in general and expand knowledge of the occurrence of MMPs in coral reef habitats.}, } @article {pmid30270425, year = {2018}, author = {Joshi, J and Guttal, V}, title = {Demographic noise and cost of greenbeard can facilitate greenbeard cooperation.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2595-2607}, doi = {10.1111/evo.13615}, pmid = {30270425}, issn = {1558-5646}, support = {DBT-IISc partnership program//Department of Biotechnology , Ministry of Science and Technology/International ; DST-FIST//Department of Science and Technology, Ministry of Science and Technology/International ; Mathematical Biology Phase II (SR/S4/MS:799/12)//Department of Science and Technology, Ministry of Science and Technology/International ; ICTS/Prog-PGE2018/03//International Centre for Theoretical Sciences/International ; }, mesh = {Adaptation, Physiological/*genetics ; Animals ; *Biological Evolution ; Game Theory ; *Models, Genetic ; Mutation ; Selection, Genetic ; }, abstract = {Cooperation among organisms, where cooperators suffer a personal cost to benefit others, is ubiquitous in nature. Greenbeard is a key mechanism for the evolution of cooperation, where a single gene or a set of linked genes codes for both cooperation and a phenotypic tag (metaphorically called "green beard"). Greenbeard cooperation is typically thought to decline over time since defectors can also evolve the tag. However, models of tag-based cooperation typically ignore two key realistic features: populations are finite, and that phenotypic tags can be costly. We develop an analytical model for coevolutionary dynamics of two evolvable traits in finite populations with mutations: costly cooperation and a costly tag. We show that an interplay of demographic noise and cost of the tag can induce coevolutionary cycling, where the evolving population does not reach a steady state but spontaneously switches between cooperative tag-carrying and noncooperative tagless states. Such dynamics allows the tag to repeatedly reappear even after it is invaded by defectors. Thus, we highlight the surprising possibility that the cost of the tag, together with demographic noise, can facilitate the evolution of greenbeard cooperation. We discuss implications of these findings in the context of the evolution of quorum sensing and multicellularity.}, } @article {pmid30270182, year = {2018}, author = {Thomas, GWC and Wang, RJ and Puri, A and Harris, RA and Raveendran, M and Hughes, DST and Murali, SC and Williams, LE and Doddapaneni, H and Muzny, DM and Gibbs, RA and Abee, CR and Galinski, MR and Worley, KC and Rogers, J and Radivojac, P and Hahn, MW}, title = {Reproductive Longevity Predicts Mutation Rates in Primates.}, journal = {Current biology : CB}, volume = {28}, number = {19}, pages = {3193-3197.e5}, pmid = {30270182}, issn = {1879-0445}, support = {HHSN272201200031C/AI/NIAID NIH HHS/United States ; P40 OD010938/OD/NIH HHS/United States ; }, mesh = {Animals ; Aotidae/genetics ; Genetic Fitness/*genetics ; Genetics, Population/methods ; Genome/genetics ; Humans ; Longevity/*genetics ; Mutation ; *Mutation Rate ; Pedigree ; Population Density ; Primates/genetics ; Reproduction ; }, abstract = {Mutation rates vary between species across several orders of magnitude, with larger organisms having the highest per-generation mutation rates. Hypotheses for this pattern typically invoke physiological or population-genetic constraints imposed on the molecular machinery preventing mutations [1]. However, continuing germline cell division in multicellular eukaryotes means that organisms with longer generation times and of larger size will leave more mutations to their offspring simply as a byproduct of their increased lifespan [2, 3]. Here, we deeply sequence the genomes of 30 owl monkeys (Aotus nancymaae) from six multi-generation pedigrees to demonstrate that paternal age is the major factor determining the number of de novo mutations in this species. We find that owl monkeys have an average mutation rate of 0.81 × 10[-8] per site per generation, roughly 32% lower than the estimate in humans. Based on a simple model of reproductive longevity that does not require any changes to the mutational machinery, we show that this is the expected mutation rate in owl monkeys. We further demonstrate that our model predicts species-specific mutation rates in other primates, including study-specific mutation rates in humans based on the average paternal age. Our results suggest that variation in life history traits alone can explain variation in the per-generation mutation rate among primates, and perhaps among a wide range of multicellular organisms.}, } @article {pmid30262973, year = {2018}, author = {Khurana, GK and Vishwakarma, P and Puri, N and Lynn, AM}, title = {Phylogenetic Analysis of the vesicular fusion SNARE machinery revealing its functional divergence across Eukaryotes.}, journal = {Bioinformation}, volume = {14}, number = {7}, pages = {361-368}, pmid = {30262973}, issn = {0973-2063}, abstract = {Proteins of the SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptors) family play a significant role in all vesicular fusion events involved in endocytic and exocytic pathways. These proteins act as molecular machines that assemble into tight four-helix bundle complex, bridging the opposing membranes into close proximity forming membrane fusion. Almost all SNARE proteins share a 53 amino acid coiled-coil domain, which is mostly linked to the transmembrane domain at the C-terminal end. Despite significant variations between SNARE sequences across species, the SNARE mediated membrane fusion is evolutionary conserved in all eukaryotes. It is of interest to compare the functional divergence of SNARE proteins across various eukaryotic groups during evolution. Here, we report an exhaustive phylogeny of the SNARE proteins retrieved from SNARE database including plants, animals, fungi and protists. The Initial phylogeny segregated SNARE protein sequences into five well-supported clades Qa, Qb, Qc, Qbc and R reflective of their positions in the four-helix SNARE complex. Further to improve resolution the Qa, Qb, Qc and R family specific trees were reconstructed, each of these were further segregated into organelle specific clades at first and later diverged into lineage specific subgroups. This revealed that most of the SNARE orthologs are conserved at subcellular locations or at trafficking pathways across various species during eukaryotic evolution. The paralogous expansion in SNARE repertoire was observed at metazoans (animals) and plants independently during eukaryotic evolution. However, results also show that the multi-cellular and saprophytic fungi have limited SNAREs.}, } @article {pmid30256189, year = {2018}, author = {Almeida, LV and Coqueiro-Dos-Santos, A and Rodriguez-Luiz, GF and McCulloch, R and Bartholomeu, DC and Reis-Cunha, JL}, title = {Chromosomal copy number variation analysis by next generation sequencing confirms ploidy stability in Trypanosoma brucei subspecies.}, journal = {Microbial genomics}, volume = {4}, number = {10}, pages = {}, pmid = {30256189}, issn = {2057-5858}, support = {BB/M028909/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 206815/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; BB/K006495/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; BB/N016165/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; G0401553/MRC_/Medical Research Council/United Kingdom ; 104111/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Chromosomes/*genetics/metabolism ; *DNA Copy Number Variations ; DNA Replication/physiology ; DNA, Protozoan/biosynthesis/genetics ; High-Throughput Nucleotide Sequencing ; In Situ Hybridization, Fluorescence ; Leishmania/genetics/metabolism ; *Phylogeny ; *Ploidies ; Species Specificity ; Trypanosoma brucei brucei/*genetics/metabolism ; Trypanosoma cruzi/*genetics/metabolism ; }, abstract = {Although aneuploidy usually results in severe abnormalities in multicellular eukaryotes, recent data suggest that it could be beneficial for unicellular eukaryotes, such as yeast and trypanosomatid parasites, providing increased survival under stressful conditions. Among characterized trypanosomatids, Trypanosoma cruzi, Trypanosoma brucei and species from the genus Leishmania stand out due to their importance in public health, infecting around 20 million people worldwide. The presence of aneuploidies in T. cruzi and Leishmania was recently confirmed by analysis based on next generation sequencing (NGS) and fluorescence in situ hybridization, where they have been associated with adaptation during transmission between their insect vectors and mammalian hosts and in promoting drug resistance. Although chromosomal copy number variations (CCNVs) are present in the aforementioned species, PFGE and fluorescence cytophotometry analyses suggest that aneuploidies are absent from T. brucei. A re-evaluation of CCNV in T. b gambiense based on NGS reads confirmed the absence of aneuploidies in this subspecies. However, the presence of aneuploidies in the other two T. brucei subspecies, T. b. brucei and T. b. rhodesiense, has not been evaluated using NGS approaches. In the present work, we tested for aneuploidies in 26 T. brucei isolates, including samples from the three T. brucei subspecies, by both allele frequency and read depth coverage analyses. These analyses showed that none of the T. brucei subspecies presents aneuploidies, which could be related to differences in the mechanisms of DNA replication and recombination in these parasites when compared with Leishmania.}, } @article {pmid30254228, year = {2018}, author = {Chen, X and Köllner, TG and Shaulsky, G and Jia, Q and Dickschat, JS and Gershenzon, J and Chen, F}, title = {Diversity and Functional Evolution of Terpene Synthases in Dictyostelid Social Amoebae.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {14361}, pmid = {30254228}, issn = {2045-2322}, support = {R35 GM118016/GM/NIGMS NIH HHS/United States ; }, mesh = {Alkyl and Aryl Transferases/*genetics/*metabolism ; Biocatalysis ; Dictyostelium/*enzymology/*genetics/growth & development/metabolism ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Phylogeny ; Species Specificity ; Terpenes/chemistry/metabolism ; Volatilization ; }, abstract = {Dictyostelids, or social amoebae, have a unique life style in forming multicellular fruiting bodies from unicellular amoeboids upon starvation. Recently, dictyostelids were found to contain terpene synthase (TPS) genes, a gene type of secondary metabolism previously known to occur only in plants, fungi and bacteria. Here we report an evolutionary functional study of dictyostelid TPS genes. The number of TPS genes in six species of dictyostelids examined ranges from 1 to 19; and the model species Dictyostelium purpureum contains 12 genes. Using in vitro enzyme assays, the 12 TPS genes from D. purpureum were shown to encode functional enzymes with distinct product profiles. The expression of the 12 TPS genes in D. purpureum is developmentally regulated. During multicellular development, D. purpureum releases a mixture of volatile terpenes dominated by sesquiterpenes that are the in vitro products of a subset of the 12 TPS genes. The quality and quantity of the terpenes released from D. purpureum, however, bear little resemblance to those of D. discoideum, a closely related dictyostelid. Despite these variations, the conserved clade of dictyostelid TPSs, which have an evolutionary distance of more than 600 million years, has the same biochemical function, catalyzing the formation of a sesquiterpene protoillud-7-ene. Taken together, our results indicate that the dynamic evolution of dictyostelid TPS genes includes both purifying selection of an orthologous group and species-specific expansion with functional divergence. Consequently, the terpenes produced by these TPSs most likely have conserved as well as species-adaptive biological functions as chemical languages in dictyostelids.}, } @article {pmid30231028, year = {2018}, author = {Lau, AYT and Cheng, X and Cheng, CK and Nong, W and Cheung, MK and Chan, RH and Hui, JHL and Kwan, HS}, title = {Discovery of microRNA-like RNAs during early fruiting body development in the model mushroom Coprinopsis cinerea.}, journal = {PloS one}, volume = {13}, number = {9}, pages = {e0198234}, pmid = {30231028}, issn = {1932-6203}, mesh = {Base Sequence ; Coprinus/*genetics ; Fruiting Bodies, Fungal/*genetics ; Fungal Proteins/genetics ; Gene Expression Regulation, Fungal ; Genome, Fungal ; Genomics ; High-Throughput Nucleotide Sequencing ; MicroRNAs/*genetics ; Phylogeny ; RNA, Fungal/*genetics ; Transcriptome ; }, abstract = {Coprinopsis cinerea is a model mushroom particularly suited for the study of fungal fruiting body development and the evolution of multicellularity in fungi. While microRNAs (miRNAs) have been extensively studied in animals and plants for their essential roles in post-transcriptional regulation of gene expression, miRNAs in fungi are less well characterized and their potential roles in controlling mushroom development remain unknown. To identify miRNA-like RNAs (milRNAs) in C. cinerea and explore their expression patterns during the early developmental transition of mushroom development, small RNA libraries of vegetative mycelium and primordium were generated and putative milRNA candidates were identified following the standards of miRNA prediction in animals and plants. Two out of 22 novel predicted milRNAs, cci-milR-12c and cci-milR-13e-5p, were validated by northern blot and stem-loop reverse transcription real-time PCR. Cci-milR-12c was differentially expressed whereas the expression levels of cci-milR-13e-5p were similar in the two developmental stages. Target prediction of the validated milRNAs resulted in genes associated with fruiting body development, including pheromone, hydrophobin, cytochrome P450, and protein kinase. Essential genes for miRNA biogenesis, including three coding for Dicer-like (DCL), one for Argonaute (AGO), one for AGO-like and one for quelling deficient-2 (QDE-2) proteins, were also identified in the C. cinerea genome. Phylogenetic analysis showed that the DCL and AGO proteins of C. cinerea were more closely related to those in other basidiomycetes and ascomycetes than to those in animals and plants. Taken together, our findings provided the first evidence for milRNAs in the model mushroom and their potential roles in regulating fruiting body development. New information on the evolutionary relationship of milRNA biogenesis proteins across kingdoms has also provided new insights for guiding further functional and evolutionary studies of miRNAs.}, } @article {pmid30225671, year = {2019}, author = {Xue, S and Dong, M and Liu, X and Xu, S and Pang, J and Zhang, W and Weng, Y and Ren, H}, title = {Classification of fruit trichomes in cucumber and effects of plant hormones on type II fruit trichome development.}, journal = {Planta}, volume = {249}, number = {2}, pages = {407-416}, pmid = {30225671}, issn = {1432-2048}, support = {31672159//National Natural Science Foundation of China/ ; 2016YFD0101705//National Key Research and Development Program of China/ ; BAIC01-2017//Project of Beijing Agricultural Innovation Consortium/ ; }, mesh = {Benzyl Compounds/pharmacology ; Cucumis sativus/*anatomy & histology/growth & development/ultrastructure ; Fruit/*anatomy & histology/growth & development/ultrastructure ; Gibberellins/pharmacology ; Microscopy, Electron, Scanning ; Plant Growth Regulators/*pharmacology ; Purines/pharmacology ; Trichomes/*classification/drug effects/growth & development/ultrastructure ; }, abstract = {Cucumber fruit trichomes could be classified into eight types; all of them are multicellular with complex and different developmental processes as compared with unicellular trichomes in other plants. The fruit trichomes or fruit spines of cucumber, Cucumis sativus L., are highly specialized structures originating from epidermal cells with diverse morphology, which grow perpendicular to the fruit surface. To understand the underlying molecular mechanisms of fruit trichome development, in this study, we conducted morphological characterization and classification of cucumber fruit trichomes and their developmental processes. We examined the fruit trichomes among 200 cucumber varieties, which could be classified into eight morphologically distinct types (I-VIII). Investigation of the organogenesis of the eight types of trichomes revealed two main developmental patterns. The development of glandular trichomes had multiple stages including initiation and expansion of the trichome precursor cell protuberating out of the epidermal surface, followed by periclinal bipartition to two cells (top and bottom) which later formed the head region and the stalk, respectively, through subsequent cell divisions. The non-glandular trichome development started with the expansion of the precursor cell perpendicularly to the epidermal plane followed by cell periclinal division to form a stalk comprising of some rectangle cells and a pointed apex cell. The base cell then started anticlinal bipartition to two cells, which then underwent many cell divisions to form a multicellular spherical structure. In addition, phytohormones as environmental cues were closely related to trichome development. We found that GA and BAP were capable of increasing trichome number per fruit with distinct effects under different concentrations.}, } @article {pmid30225080, year = {2018}, author = {Herron, MD and Ratcliff, WC and Boswell, J and Rosenzweig, F}, title = {Genetics of a de novo origin of undifferentiated multicellularity.}, journal = {Royal Society open science}, volume = {5}, number = {8}, pages = {180912}, pmid = {30225080}, issn = {2054-5703}, abstract = {The evolution of multicellularity was a major transition in evolution and set the stage for unprecedented increases in complexity, especially in land plants and animals. Here, we explore the genetics underlying a de novo origin of multicellularity in a microbial evolution experiment carried out on the green alga Chlamydomonas reinhardtii. We show that large-scale changes in gene expression underlie the transition to a multicellular life cycle. Among these, changes to genes involved in cell cycle and reproductive processes were overrepresented, as were changes to C. reinhardtii-specific and volvocine-specific genes. These results suggest that the genetic basis for the experimental evolution of multicellularity in C. reinhardtii has both lineage-specific and shared features, and that the shared features have more in common with C. reinhardtii's relatives among the volvocine algae than with other multicellular green algae or land plants.}, } @article {pmid30220504, year = {2018}, author = {De Clerck, O and Kao, SM and Bogaert, KA and Blomme, J and Foflonker, F and Kwantes, M and Vancaester, E and Vanderstraeten, L and Aydogdu, E and Boesger, J and Califano, G and Charrier, B and Clewes, R and Del Cortona, A and D'Hondt, S and Fernandez-Pozo, N and Gachon, CM and Hanikenne, M and Lattermann, L and Leliaert, F and Liu, X and Maggs, CA and Popper, ZA and Raven, JA and Van Bel, M and Wilhelmsson, PKI and Bhattacharya, D and Coates, JC and Rensing, SA and Van Der Straeten, D and Vardi, A and Sterck, L and Vandepoele, K and Van de Peer, Y and Wichard, T and Bothwell, JH}, title = {Insights into the Evolution of Multicellularity from the Sea Lettuce Genome.}, journal = {Current biology : CB}, volume = {28}, number = {18}, pages = {2921-2933.e5}, doi = {10.1016/j.cub.2018.08.015}, pmid = {30220504}, issn = {1879-0445}, mesh = {*Biological Evolution ; Chromosome Mapping ; *Genome ; *Life History Traits ; Multigene Family ; Ulva/*genetics/growth & development ; }, abstract = {We report here the 98.5 Mbp haploid genome (12,924 protein coding genes) of Ulva mutabilis, a ubiquitous and iconic representative of the Ulvophyceae or green seaweeds. Ulva's rapid and abundant growth makes it a key contributor to coastal biogeochemical cycles; its role in marine sulfur cycles is particularly important because it produces high levels of dimethylsulfoniopropionate (DMSP), the main precursor of volatile dimethyl sulfide (DMS). Rapid growth makes Ulva attractive biomass feedstock but also increasingly a driver of nuisance "green tides." Ulvophytes are key to understanding the evolution of multicellularity in the green lineage, and Ulva morphogenesis is dependent on bacterial signals, making it an important species with which to study cross-kingdom communication. Our sequenced genome informs these aspects of ulvophyte cell biology, physiology, and ecology. Gene family expansions associated with multicellularity are distinct from those of freshwater algae. Candidate genes, including some that arose following horizontal gene transfer from chromalveolates, are present for the transport and metabolism of DMSP. The Ulva genome offers, therefore, new opportunities to understand coastal and marine ecosystems and the fundamental evolution of the green lineage.}, } @article {pmid30218496, year = {2018}, author = {Kulkarni, P and Uversky, VN}, title = {Intrinsically Disordered Proteins: The Dark Horse of the Dark Proteome.}, journal = {Proteomics}, volume = {18}, number = {21-22}, pages = {e1800061}, doi = {10.1002/pmic.201800061}, pmid = {30218496}, issn = {1615-9861}, mesh = {Animals ; Humans ; Intrinsically Disordered Proteins/*chemistry/*metabolism ; Protein Conformation ; Proteome/chemistry/metabolism ; }, abstract = {A good portion of the 'protein universe' embodies the 'dark proteome'. The latter comprises proteins not amenable to experimental structure determination by existing means and inaccessible to homology modeling. Hence, the dark proteome has remained largely unappreciated. Intrinsically disordered proteins (IDPs) that lack rigid 3D structure are a major component of this dark proteome across all three kingdoms of life. Despite lack of structure, IDPs play critical roles in numerous important biological processes. Furthermore, IDPs serve as crucial constituents of proteinaceous membrane-less organelles (PMLOs), where they often serve as drivers and controllers of biological liquid-liquid phase transitions responsible for the PMLO biogenesis. In this perspective, the role of IDPs is discussed in i) the origin of prebiotic life and the evolution of the first independent primordial living unit akin to Tibor Gánti's chemoton, which preceded the Last Universal Common Ancestor (LUCA), ii) role in multicellularity and hence, in major evolutionary transitions, and iii), their role in phenotypic switching, and the emergence of new traits and adaptive opportunities via non-genetic, protein-based mechanisms. The emerging picture suggests that despite being major constituents of the dark matter, IDPs may be the dark horse in the protein universe.}, } @article {pmid30214674, year = {2018}, author = {Baluška, F and Miller, WB}, title = {Senomic view of the cell: Senome versus Genome.}, journal = {Communicative & integrative biology}, volume = {11}, number = {3}, pages = {1-9}, pmid = {30214674}, issn = {1942-0889}, abstract = {In the legacy of Thomas Henry Huxley, and his 'epigenetic' philosophy of biology, cells are proposed to represent a trinity of three memory-storing media: Senome, Epigenome, and Genome that together comprise a cell-wide informational architecture. Our current preferential focus on the Genome needs to be complemented by a similar focus on the Epigenome and a here proposed Senome, representing the sum of all the sensory experiences of the cognitive cell and its sensing apparatus. Only then will biology be in a position to embrace the whole complexity of the eukaryotic cell, understanding its true nature which allows the communicative assembly of cells in the form of sentient multicellular organisms.}, } @article {pmid30212236, year = {2018}, author = {Zhang, L and Vijg, J}, title = {Somatic Mutagenesis in Mammals and Its Implications for Human Disease and Aging.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {397-419}, pmid = {30212236}, issn = {1545-2948}, support = {U01 HL145560/HL/NHLBI NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; R01 CA180126/CA/NCI NIH HHS/United States ; P30 AG038072/AG/NIA NIH HHS/United States ; P01 AG017242/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*genetics/pathology ; Clonal Evolution/genetics ; Genetic Diseases, Inborn/*genetics/pathology ; Genome, Human/*genetics ; Germ-Line Mutation/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Mutagenesis/*genetics ; Mutation/genetics ; }, abstract = {DNA mutations as a consequence of errors during DNA damage repair, replication, or mitosis are the substrate for evolution. In multicellular organisms, mutations can occur in the germline and also in somatic tissues, where they are associated with cancer and other chronic diseases and possibly with aging. Recent advances in high-throughput sequencing have made it relatively easy to study germline de novo mutations, but in somatic cells, the vast majority of mutations are low-abundant and can be detected only in clonal lineages, such as tumors, or single cells. Here we review recent results on somatic mutations in normal human and animal tissues with a focus on their possible functional consequences.}, } @article {pmid30199707, year = {2018}, author = {Niazi, S and Purohit, M and Niazi, JH}, title = {Role of p53 circuitry in tumorigenesis: A brief review.}, journal = {European journal of medicinal chemistry}, volume = {158}, number = {}, pages = {7-24}, doi = {10.1016/j.ejmech.2018.08.099}, pmid = {30199707}, issn = {1768-3254}, mesh = {Animals ; Carcinogenesis/drug effects/*metabolism/pathology ; Drug Discovery ; Humans ; Models, Molecular ; Proteasome Endopeptidase Complex/metabolism ; Protein Isoforms/metabolism ; Proto-Oncogene Proteins c-mdm2/metabolism ; Tumor Suppressor Protein p53/*metabolism ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism ; }, abstract = {Maintenance of genome integrity under the stressed condition is paramount for normal functioning of cells in the multicellular organisms. Cells are programmed to protect their genome through specialized adaptive mechanisms which will help decide their fate under stressed conditions. These mechanisms are the outcome of activation of the intricate circuitries that are regulated by the p53 master protein. In this paper, we provided a comprehensive review on p53, p53 homologues and their isoforms, including a description about the ubiquitin-proteasome system emphasizing its role in p53 regulation. p53 induced E3(Ub)-ligases are an integral part of the ubiquitin-proteasome system. This review outlines the roles of important E3(Ub)-ligases and their splice variants in maintaining cellular p53 protein homeostasis. It also covers up-to-date and relevant information on small molecule Mdm2 inhibitors originated from different organizations. The review ends with a discussion on future prospects and investigation directives for the development of next-generation modulators as p53 therapeutics.}, } @article {pmid30191307, year = {2019}, author = {Váchová, L and Palková, Z}, title = {Diverse roles of Tup1p and Cyc8p transcription regulators in the development of distinct types of yeast populations.}, journal = {Current genetics}, volume = {65}, number = {1}, pages = {147-151}, pmid = {30191307}, issn = {1432-0983}, support = {LQ1604 NPU II//Ministry of Education, Youth and Sports/ ; RVO61388971//Czech Academy of Sciences/ ; CZ.1.05/1.1.00/02.0109 BIOCEV//European Regional Development Fund and Ministry of Education, Youth and Sports/ ; }, mesh = {Biofilms ; Cell Wall/genetics/metabolism ; *Gene Expression Regulation, Fungal ; Nuclear Proteins/*genetics/metabolism ; Repressor Proteins/*genetics/metabolism ; Saccharomyces cerevisiae/classification/*genetics/physiology ; Saccharomyces cerevisiae Proteins/*genetics/metabolism ; Species Specificity ; }, abstract = {Yeasts create multicellular structures of varying complexity, such as more complex colonies and biofilms and less complex flocs, each of which develops via different mechanisms. Colony biofilms originate from one or more cells that, through growth and division, develop a complicated three-dimensional structure consisting of aerial parts, agar-embedded invasive parts and a central cavity, filled with extracellular matrix. In contrast, flocs arise relatively quickly by aggregation of planktonic cells growing in liquid cultures after they reach the appropriate growth phase and/or exhaust nutrients such as glucose. Creation of both types of structures is dependent on the presence of flocculins: Flo11p in the former case and Flo1p in the latter. We recently showed that formation of both types of structures by wild Saccharomyces cerevisiae strain BR-F is regulated via transcription regulators Tup1p and Cyc8p, but in a divergent manner. Biofilm formation is regulated by Cyc8p and Tup1p antagonistically: Cyc8p functions as a repressor of FLO11 gene expression and biofilm formation, whereas Tup1p counteracts the Cyc8p repressor function and positively regulates biofilm formation and Flo11p expression. In addition, Tup1p stabilizes Flo11p probably by repressing a gene coding for a cell wall or extracellular protease that is involved in Flo11p degradation. In contrast, formation of BR-F flocs is co-repressed by the Cyc8p-Tup1p complex. These findings point to different mechanisms involved in yeast multicellularity.}, } @article {pmid30180336, year = {2019}, author = {Norouzitallab, P and Baruah, K and Vanrompay, D and Bossier, P}, title = {Can epigenetics translate environmental cues into phenotypes?.}, journal = {The Science of the total environment}, volume = {647}, number = {}, pages = {1281-1293}, doi = {10.1016/j.scitotenv.2018.08.063}, pmid = {30180336}, issn = {1879-1026}, mesh = {*Cues ; *Epigenesis, Genetic ; *Phenotype ; }, abstract = {Living organisms are constantly exposed to wide ranges of environmental cues. They react to these cues by undergoing a battery of phenotypic responses, such as by altering their physiological and behavioral traits, in order to adapt and survive in the changed environments. The adaptive response of a species induced by environmental cues is typically thought to be associated with its genetic diversity such that higher genetic diversity provides increased adaptive potential. This originates from the general consensus that phenotypic traits have a genetic basis and are subject to Darwinian natural selection and Mendelian inheritance. There is no doubt about the validity of these principles, supported by the successful introgression of specific traits during (selective) breeding. However, a range of recent studies provided fascinating evidences suggesting that environmental effects experienced by an organism during its lifetime can have marked influences on its phenotype, and additionally the organism can pass on the acquired phenotypes to its subsequent generations through non-genetic mechanisms (also termed as epigenetic mechanism) - a notion that dates back to Lamarck and has been controversial ever since. In this review, we describe how the epigenetics has reshaped our long perception about the inheritance/development of phenotypes within organisms, contrasting with the classical gene-based view of inheritance. We particularly highlighted recent developments in our understanding of inheritance of parental environmental induced phenotypic traits in multicellular organisms under different environmental conditions, and discuss how modifications of the epigenome contribute to the determination of the adult phenotype of future generations.}, } @article {pmid30177944, year = {2018}, author = {Yruela, I and Contreras-Moreira, B and Dunker, AK and Niklas, KJ}, title = {Evolution of Protein Ductility in Duplicated Genes of Plants.}, journal = {Frontiers in plant science}, volume = {9}, number = {}, pages = {1216}, pmid = {30177944}, issn = {1664-462X}, abstract = {Previous work has shown that ductile/intrinsically disordered proteins (IDPs) and residues (IDRs) are found in all unicellular and multicellular organisms, wherein they are essential for basic cellular functions and complement the function of rigid proteins. In addition, computational studies of diverse phylogenetic lineages have revealed: (1) that protein ductility increases in concert with organismic complexity, and (2) that distributions of IDPs and IDRs along the chromosomes of plant species are non-random and correlate with variations in the rates of the genetic recombination and chromosomal rearrangement. Here, we show that approximately 50% of aligned residues in paralogs across a spectrum of algae, bryophytes, monocots, and eudicots are IDRs and that a high proportion (ca. 60%) are in disordered segments greater than 30 residues. When three types of IDRs are distinguished (i.e., identical, similar and variable IDRs) we find that species with large numbers of chromosome and endoduplicated genes exhibit paralogous sequences with a higher frequency of identical IDRs, whereas species with small chromosomes numbers exhibit paralogous sequences with a higher frequency of similar and variable IDRs. These results are interpreted to indicate that genome duplication events influence the distribution of IDRs along protein sequences and likely favor the presence of identical IDRs (compared to similar IDRs or variable IDRs). We discuss the evolutionary implications of gene duplication events in the context of ductile/disordered residues and segments, their conservation, and their effects on functionality.}, } @article {pmid30177778, year = {2018}, author = {Waters, AJ and Capriotti, P and Gaboriau, DCA and Papathanos, PA and Windbichler, N}, title = {Rationally-engineered reproductive barriers using CRISPR & CRISPRa: an evaluation of the synthetic species concept in Drosophila melanogaster.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {13125}, pmid = {30177778}, issn = {2045-2322}, support = {335724/ERC_/European Research Council/International ; }, mesh = {Animals ; Base Sequence ; CRISPR-Associated Protein 9/genetics/metabolism ; *CRISPR-Cas Systems ; Drosophila Proteins/*genetics ; Drosophila melanogaster/*genetics ; Female ; Gene Editing/*methods ; *Genes, Insect ; Genes, Lethal ; Genetic Fitness ; Genetic Loci ; *Genome, Insect ; Homeodomain Proteins/*genetics ; INDEL Mutation ; Male ; Population Control/methods ; Promoter Regions, Genetic ; RNA, Guide, Kinetoplastida/genetics/metabolism ; Reproductive Isolation ; Sequence Alignment ; Transcription Factors/*genetics ; Transcriptional Activation ; }, abstract = {The ability to erect rationally-engineered reproductive barriers in animal or plant species promises to enable a number of biotechnological applications such as the creation of genetic firewalls, the containment of gene drives or novel population replacement and suppression strategies for genetic control. However, to date no experimental data exist that explores this concept in a multicellular organism. Here we examine the requirements for building artificial reproductive barriers in the metazoan model Drosophila melanogaster by combining CRISPR-based genome editing and transcriptional transactivation (CRISPRa) of the same loci. We directed 13 single guide RNAs (sgRNAs) to the promoters of 7 evolutionary conserved genes and used 11 drivers to conduct a misactivation screen. We identify dominant-lethal activators of the eve locus and find that they disrupt development by strongly activating eve outside its native spatio-temporal context. We employ the same set of sgRNAs to isolate, by genome editing, protective INDELs that render these loci resistant to transactivation without interfering with target gene function. When these sets of genetic components are combined we find that complete synthetic lethality, a prerequisite for most applications, is achievable using this approach. However, our results suggest a steep trade-off between the level and scope of dCas9 expression, the degree of genetic isolation achievable and the resulting impact on fly fitness. The genetic engineering strategy we present here allows the creation of single or multiple reproductive barriers and could be applied to other multicellular organisms such as disease vectors or transgenic organisms of economic importance.}, } @article {pmid30172691, year = {2018}, author = {Olejarz, J and Kaveh, K and Veller, C and Nowak, MA}, title = {Selection for synchronized cell division in simple multicellular organisms.}, journal = {Journal of theoretical biology}, volume = {457}, number = {}, pages = {170-179}, pmid = {30172691}, issn = {1095-8541}, mesh = {Cell Cycle/*physiology ; *Evolution, Molecular ; *Models, Biological ; *Selection, Genetic ; }, abstract = {The evolution of multicellularity was a major transition in the history of life on earth. Conditions under which multicellularity is favored have been studied theoretically and experimentally. But since the construction of a multicellular organism requires multiple rounds of cell division, a natural question is whether these cell divisions should be synchronous or not. We study a population model in which there compete simple multicellular organisms that grow by either synchronous or asynchronous cell divisions. We demonstrate that natural selection can act differently on synchronous and asynchronous cell division, and we offer intuition for why these phenotypes are generally not neutral variants of each other.}, } @article {pmid30171399, year = {2018}, author = {Liu, Y and Liu, D and Khan, AR and Liu, B and Wu, M and Huang, L and Wu, J and Song, G and Ni, H and Ying, H and Yu, H and Gan, Y}, title = {NbGIS regulates glandular trichome initiation through GA signaling in tobacco.}, journal = {Plant molecular biology}, volume = {98}, number = {1-2}, pages = {153-167}, pmid = {30171399}, issn = {1573-5028}, support = {31570183; 31529001; 31661143004//National Natural Science Foundation of China/ ; LZ15C020001//Zhejiang Provincial Natural Science Foundation of China/ ; 2015CB150200//Major State Basic Research Development Program/ ; 2016YFD0100701//the National Key R & D Program of China/ ; }, mesh = {Amino Acid Sequence ; Biosynthetic Pathways/genetics ; Gene Expression Regulation, Plant ; Genes, Plant ; Gibberellins/biosynthesis/*metabolism ; Phenotype ; Phylogeny ; Plant Development/genetics ; Plant Proteins/chemistry/*metabolism ; Plant Shoots/physiology ; Plants, Genetically Modified ; *Signal Transduction ; Tobacco/genetics/growth & development/*metabolism ; Trichomes/*growth & development/*metabolism/ultrastructure ; }, abstract = {A novel gene NbGIS positively regulates glandular trichome initiation through GA Signaling in tobacco. NbMYB123-like regulates glandular trichome initiation by acting downstream of NbGIS in tobacco. Glandular trichome is a specialized multicellular structure which has capability to synthesize and secrete secondary metabolites and protects plants from biotic and abiotic stresses. Our previous results revealed that a C2H2 zinc-finger transcription factor GIS and its sub-family genes act upstream of GL3/EGL3-GL1-TTG1 transcriptional activator complex to regulate trichome initiation in Arabidopsis. In this present study, we found that NbGIS could positively regulate glandular trichome development in Nicotiana benthamiana (tobacco). Our result demonstrated that 35S:NbGIS lines exhibited much higher densities of trichome on leaves, main stems, lateral branches and sepals than WT plants, while NbGIS:RNAi lines had the opposite phenotypes. Furthermore, our results also showed that NbGIS was required in response to GA signal to control glandular trichome initiation in Nicotiana benthamiana. In addition, our results also showed that NbGIS significantly influenced GA accumulation and expressions of marker genes of the GA biosynthesis, might result in the changes of growth and maturation in tobacco. Lastly, our results also showed that NbMYB123-like regulated glandular trichome initiation in tobacco by acting downstream of NbGIS. These findings provide new insights to discover the molecular mechanism by which C2H2 transcriptional factors regulates glandular trichome initiation through GA signaling pathway in tobacco.}, } @article {pmid30170750, year = {2018}, author = {Atkinson, SD and Bartholomew, JL and Lotan, T}, title = {Myxozoans: Ancient metazoan parasites find a home in phylum Cnidaria.}, journal = {Zoology (Jena, Germany)}, volume = {129}, number = {}, pages = {66-68}, doi = {10.1016/j.zool.2018.06.005}, pmid = {30170750}, issn = {1873-2720}, mesh = {Animals ; Biological Evolution ; Cnidaria/*parasitology ; Host-Parasite Interactions ; Myxozoa/genetics/*physiology ; Parasites ; }, abstract = {Myxozoans are endoparasites with complex life cycles that alternate between invertebrate and vertebrate hosts. Though considered protozoans for over 150 years, they are now recognized as metazoans, given their multicellularity and ultrastructural features. In recognition of synapomorphies and cnidarian-specific genes, myxozoans were placed recently within the phylum Cnidaria. Although they have lost genetic and structural complexity on the path to parasitism, myxozoans have retained characteristic cnidarian cnidocysts, but use them for initiating host infection. Myxozoans represent at least 20% of phylum Cnidaria, but as a result of rapid evolution, extensive diversification and host specialization, they are probably at least as diverse as their free-living relatives. The ability of myxozoans to infect freshwater, marine and terrestrial hosts implies that Cnidaria are no longer constrained to the aquatic environment.}, } @article {pmid30159848, year = {2018}, author = {Chi, C and Wang, L and Lan, W and Zhao, L and Su, Y}, title = {PpV, acting via the JNK pathway, represses apoptosis during normal development of Drosophila wing.}, journal = {Apoptosis : an international journal on programmed cell death}, volume = {23}, number = {9-10}, pages = {554-562}, doi = {10.1007/s10495-018-1479-2}, pmid = {30159848}, issn = {1573-675X}, mesh = {Animals ; Apoptosis/*genetics ; Drosophila melanogaster/genetics/growth & development ; Embryonic Development/genetics ; Gene Expression Regulation, Developmental ; Imaginal Discs/growth & development/metabolism ; JNK Mitogen-Activated Protein Kinases/*genetics ; MAP Kinase Signaling System/genetics ; Phosphoprotein Phosphatases/*genetics ; Wings, Animal/*growth & development/metabolism ; }, abstract = {Apoptosis is one of the main fundamental biological processes required for development of multicellular organisms. Inappropriate regulation of apoptosis can lead to severe developmental abnormalities and diseases. Therefore, the control of apoptosis, not only for its activation but also for its inhibition, is critically important during development. In contrast to the extensive studies of apoptosis induction, its inhibitory mechanisms that are even more vital in certain populations of cells actually are very far from being well understood. Here we report an inhibitory role of protein phosphatase V (PpV), a serine/threonine protein phosphatase, in controlling the apoptosis during Drosophila wing development. We observed that inhibition of ppv by RNAi in wing imaginal discs induced ectopic cell death and caspase activation, thus, resulted in a defective adult wing. Moreover, knocking-down ppv triggered the activation of c-Jun N-terminal kinase (JNK) signal, an evolutionarily conserved intracellular signaling that has been implicated to modulate the apoptotic machinery in many biological and experimental systems. Disrupting the JNK signal transduction was adequate to suppress the ppv effects for wing development. Together, we provided the evidence to demonstrate that ppv is required for normal wing development in maintaining the silence of apoptotic signal possibly through JNK pathway.}, } @article {pmid30158313, year = {2018}, author = {Bernadou, A and Schrader, L and Pable, J and Hoffacker, E and Meusemann, K and Heinze, J}, title = {Stress and early experience underlie dominance status and division of labour in a clonal insect.}, journal = {Proceedings. Biological sciences}, volume = {285}, number = {1885}, pages = {}, pmid = {30158313}, issn = {1471-2954}, mesh = {Animals ; Ants/growth & development/*physiology ; Larva/growth & development/physiology ; Life Change Events ; Population Dynamics ; Social Dominance ; *Stress, Physiological ; }, abstract = {Cooperation and division of labour are fundamental in the 'major transitions' in evolution. While the factors regulating cell differentiation in multi-cellular organisms are quite well understood, we are just beginning to unveil the mechanisms underlying individual specialization in cooperative groups of animals. Clonal ants allow the study of which factors influence task allocation without confounding variation in genotype and morphology. Here, we subjected larvae and freshly hatched workers of the clonal ant Platythyrea punctata to different rearing conditions and investigated how these manipulations affected division of labour among pairs of oppositely treated, same-aged clonemates. High rearing temperature, physical stress, injury and malnutrition increased the propensity of individuals to become subordinate foragers rather than dominant reproductives. This is reflected in changed gene regulation: early stages of division of labour were associated with different expression of genes involved in nutrient signalling pathways, metabolism and the phenotypic response to environmental stimuli. Many of these genes appear to be capable of responding to a broad range of stressors. They might link environmental stimuli to behavioural and phenotypic changes and could therefore be more broadly involved in caste differentiation in social insects. Our experiments also shed light on the causes of behavioural variation among genetically identical individuals.}, } @article {pmid30149856, year = {2018}, author = {Strauss, J and Wilkinson, C and Vidilaseris, K and Harborne, SPD and Goldman, A}, title = {A Simple Strategy to Determine the Dependence of Membrane-Bound Pyrophosphatases on K[+] as a Cofactor.}, journal = {Methods in enzymology}, volume = {607}, number = {}, pages = {131-156}, doi = {10.1016/bs.mie.2018.04.018}, pmid = {30149856}, issn = {1557-7988}, support = {BB/M021610/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Catalysis ; Cations, Monovalent/metabolism ; Cell Membrane/*metabolism ; Coenzymes/*metabolism ; Diphosphates/metabolism ; Enzyme Assays/instrumentation/*methods ; Hydrolysis ; Models, Molecular ; Mutagenesis, Site-Directed ; Potassium/*metabolism ; Pyrophosphatases/chemistry/genetics/isolation & purification/*metabolism ; Recombinant Proteins/chemistry/genetics/isolation & purification/metabolism ; Saccharomyces cerevisiae ; }, abstract = {Membrane-bound pyrophosphatases (mPPases) couple pyrophosphate hydrolysis to H[+] and/or Na[+] pumping across membranes and are found in all domains of life except for multicellular animals including humans. They are important for development and stress resistance in plants. Furthermore, mPPases play a role in virulence of human pathogens that cause severe diseases such as malaria and African sleeping sickness. Sequence analysis, functional studies, and recently solved crystal structures have contributed to the understanding of the mPPase catalytic cycle. However, several key mechanistic features remain unknown. During evolution, several subgroups of mPPases differing in their pumping specificity and cofactor dependency arose. mPPases are classified into one of five subgroups, usually by sequence analysis. However, classification based solely on sequence has been inaccurate in several instances due to our limited understanding of the molecular mechanism of mPPases. Thus, pumping specificity and cofactor dependency of mPPases require experimental confirmation. Here, we describe a simple method for the determination of K[+] dependency in mPPases using a hydrolytic activity assay. By coupling these dependency studies with site-directed mutagenesis, we have begun to build a better understanding of the molecular mechanisms of mPPases. We optimized the assay for thermostable mPPases that are commonly used as model systems in our lab, but the method is equally applicable to mesophilic mPPases with minor modifications.}, } @article {pmid30134151, year = {2018}, author = {Stone, R and Portegys, T and Mikhailovsky, G and Alicea, B}, title = {Origins of the Embryo: Self-organization through cybernetic regulation.}, journal = {Bio Systems}, volume = {173}, number = {}, pages = {73-82}, doi = {10.1016/j.biosystems.2018.08.005}, pmid = {30134151}, issn = {1872-8324}, mesh = {Algorithms ; Animals ; Biological Evolution ; *Cybernetics ; Developmental Biology/history ; Ecosystem ; *Embryonic Development ; Entropy ; History, 19th Century ; History, 20th Century ; Humans ; *Models, Biological ; Phenotype ; Thermodynamics ; }, abstract = {The construction of an embryo from a single cell precursor is a highly complex process. Evolutionary emergence of the first embryos is even more complex, and involves both a transition to multicellularity along with the establishment of developmental mechanisms. We propose that embryogenesis relies on a community of cells conforming to a regulatory model of emergent multicellularity. This model draws together multiple threads in the scientific literature, from complexity theory to cybernetics, and from thermodynamic entropy to artificial life. All of these strands come together to inform a model of goal-oriented regulation for emergent structures in early life. This is an important step in the evolution of early life, as well as the emergence of complex life in the earliest habitats. Our model, called the cybernetic embryo, allows for a systems-level view of the embryogenetic process.}, } @article {pmid30125231, year = {2018}, author = {Hanschen, ER and Herron, MD and Wiens, JJ and Nozaki, H and Michod, RE}, title = {Multicellularity Drives the Evolution of Sexual Traits.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {E93-E105}, pmid = {30125231}, issn = {1537-5323}, support = {NNA17BB05A//Intramural NASA/United States ; }, mesh = {*Biological Evolution ; Chlamydomonas reinhardtii/*genetics ; Meiosis ; *Sex Characteristics ; Volvox/*genetics ; }, abstract = {From the male peacock's tail plumage to the floral displays of flowering plants, traits related to sexual reproduction are often complex and exaggerated. Why has sexual reproduction become so complicated? Why have such exaggerated sexual traits evolved? Early work posited a connection between multicellularity and sexual traits such as anisogamy (i.e., the evolution of small sperm and large eggs). Anisogamy then drives the evolution of other forms of sexual dimorphism. Yet the relationship between multicellularity and the evolution of sexual traits has not been empirically tested. Given their extensive variation in both multicellular complexity and sexual systems, the volvocine green algae offer a tractable system for understanding the interrelationship of multicellular complexity and sex. Here we show that species with greater multicellular complexity have a significantly larger number of derived sexual traits, including anisogamy, internal fertilization, and secondary sexual dimorphism. Our results demonstrate that anisogamy repeatedly evolved from isogamous multicellular ancestors and that anisogamous species are larger and produce larger zygotes than isogamous species. In the volvocine algae, the evolution of multicellularity likely drives the evolution of anisogamy, and anisogamy subsequently drives secondary sexual dimorphism. Multicellularity may set the stage for the overall diversity of sexual complexity throughout the Tree of Life.}, } @article {pmid30113099, year = {2018}, author = {Stelbrink, B and Jovanovska, E and Levkov, Z and Ognjanova-Rumenova, N and Wilke, T and Albrecht, C}, title = {Diatoms do radiate: evidence for a freshwater species flock.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1969-1975}, doi = {10.1111/jeb.13368}, pmid = {30113099}, issn = {1420-9101}, mesh = {Diatoms/*genetics/*physiology ; *Evolution, Molecular ; Fossils ; *Fresh Water ; *Genetic Variation ; *Phylogeny ; Time Factors ; }, abstract = {Due to the ubiquity and high dispersal capacity of unicellular eukaryotes, their often extraordinary diversity found in isolated and long-lived ecosystems such as ancient lakes is typically attributed to multiple colonization events rather than to in situ speciation. However, respective evolutionary studies are very scarce and the often high number of species flocks in ancient lakes across multicellular taxa raises the question whether unicellular species, such as diatoms, may radiate as well. Here, we use an integrative approach that includes molecular data from benthic diatom species of the genus Aneumastus endemic to ancient Lake Ohrid, fossil data obtained from the sediment record of a recent deep-drilling project and biogeographical information to test if this group, indeed, constitutes a species flock. Molecular-clock and phylogenetic analyses indicate a young monophyletic group of several endemic species. Molecular, fossil and biogeographical data strongly suggest a rapid intralacustrine diversification, which was possibly triggered by the emergence of novel habitats. This finding is the first evidence for a species flock in diatoms and suggests that in situ speciation is also a relevant evolutionary process for unicellular eukaryotes in isolated ecosystems.}, } @article {pmid30111663, year = {2018}, author = {Grimes, DR and Currell, FJ}, title = {Oxygen diffusion in ellipsoidal tumour spheroids.}, journal = {Journal of the Royal Society, Interface}, volume = {15}, number = {145}, pages = {}, pmid = {30111663}, issn = {1742-5662}, support = {A19834/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Cell Line, Tumor ; Humans ; *Models, Biological ; Neoplasms/*metabolism/pathology ; Oxygen/*metabolism ; *Oxygen Consumption ; Spheroids, Cellular/*metabolism/pathology ; }, abstract = {Oxygen plays a central role in cellular metabolism, in both healthy and tumour tissue. The presence and concentration of molecular oxygen in tumours has a substantial effect on both radiotherapy response and tumour evolution, and as a result the oxygen micro-environment is an area of intense research interest. Multi-cellular tumour spheroids closely mimic real avascular tumours, and in particular they exhibit physiologically relevant heterogeneous oxygen distribution. This property has made them a vital part of in vitro experimentation. For ideal spheroids, their heterogeneous oxygen distributions can be predicted from theory, allowing determination of cellular oxygen consumption rate (OCR) and anoxic extent. However, experimental tumour spheroids often depart markedly from perfect sphericity. There has been little consideration of this reality. To date, the question of how far an ellipsoid can diverge from perfect sphericity before spherical assumptions break down remains unanswered. In this work, we derive equations governing oxygen distribution (and, more generally, nutrient and drug distribution) in both prolate and oblate tumour ellipsoids, and quantify the theoretical limits of the assumption that the spheroid is a perfect sphere. Results of this analysis yield new methods for quantifying OCR in ellipsoidal spheroids, and how this can be applied to markedly increase experimental throughput and quality.}, } @article {pmid30109121, year = {2018}, author = {Wang, X and Zhu, W and Chang, P and Wu, H and Liu, H and Chen, J}, title = {Merge and separation of NuA4 and SWR1 complexes control cell fate plasticity in Candida albicans.}, journal = {Cell discovery}, volume = {4}, number = {}, pages = {45}, pmid = {30109121}, issn = {2056-5968}, support = {R01 AI099190/AI/NIAID NIH HHS/United States ; R01 GM117111/GM/NIGMS NIH HHS/United States ; }, abstract = {Phenotypic plasticity is common in development. Candida albicans, a polymorphic fungal pathogen of humans, possesses the unique ability to achieve rapid and reversible cell fate between unicellular form (yeast) and multicellular form (hypha) in response to environmental cues. The NuA4 histone acetyltransferase activity and Hda1 histone deacetylase activity have been reported to be required for hyphal initiation and maintenance. However, how Hda1 and NuA4 regulate hyphal elongation is not clear. NuA4 histone acetyltransferase and SWR1 chromatin remodeling complexes are conserved from yeast to human, which may have merged together to form a larger TIP60 complex since the origin of metazoan. In this study, we show a dynamic merge and separation of NuA4 and SWR1 complexes in C. albicans. NuA4 and SWR1 merge together in yeast state and separate into two distinct complexes in hyphal state. We demonstrate that acetylation of Eaf1 K173 controls the interaction between the two complexes. The YEATS domain of Yaf9 in C. albicans can recognize an acetyl-lysine of the Eaf1 and mediate the Yaf9-Eaf1 interaction. The reversible acetylation and deacetylation of Eaf1 by Esa1 and Hda1 control the merge and separation of NuA4 and SWR1, and this regulation is triggered by Brg1 recruitment of Hda1 to chromatin in response nutritional signals that sustain hyphal elongation. We have also observed an orchestrated promoter association of Esa1, Hda1, Swr1, and H2A.Z during the reversible yeast-hyphae transitions. This is the first discovery of a regulated merge of the NuA4 and SWR1 complexes that controls cell fate determination and this regulation may be conserved in polymorphic fungi.}, } @article {pmid30103474, year = {2018}, author = {Mattick, JS}, title = {The State of Long Non-Coding RNA Biology.}, journal = {Non-coding RNA}, volume = {4}, number = {3}, pages = {}, pmid = {30103474}, issn = {2311-553X}, abstract = {Transcriptomic studies have demonstrated that the vast majority of the genomes of mammals and other complex organisms is expressed in highly dynamic and cell-specific patterns to produce large numbers of intergenic, antisense and intronic long non-protein-coding RNAs (lncRNAs). Despite well characterized examples, their scaling with developmental complexity, and many demonstrations of their association with cellular processes, development and diseases, lncRNAs are still to be widely accepted as major players in gene regulation. This may reflect an underappreciation of the extent and precision of the epigenetic control of differentiation and development, where lncRNAs appear to have a central role, likely as organizational and guide molecules: most lncRNAs are nuclear-localized and chromatin-associated, with some involved in the formation of specialized subcellular domains. I suggest that a reassessment of the conceptual framework of genetic information and gene expression in the 4-dimensional ontogeny of spatially organized multicellular organisms is required. Together with this and further studies on their biology, the key challenges now are to determine the structure[-]function relationships of lncRNAs, which may be aided by emerging evidence of their modular structure, the role of RNA editing and modification in enabling epigenetic plasticity, and the role of RNA signaling in transgenerational inheritance of experience.}, } @article {pmid30102347, year = {2018}, author = {Gaouda, H and Hamaji, T and Yamamoto, K and Kawai-Toyooka, H and Suzuki, M and Noguchi, H and Minakuchi, Y and Toyoda, A and Fujiyama, A and Nozaki, H and Smith, DR}, title = {Exploring the Limits and Causes of Plastid Genome Expansion in Volvocine Green Algae.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2248-2254}, pmid = {30102347}, issn = {1759-6653}, mesh = {Chlorophyta/genetics ; DNA, Algal/*genetics ; Evolution, Molecular ; *Genome, Plastid ; Plastids/genetics ; Sequence Analysis, DNA ; Volvox/*genetics ; }, abstract = {Plastid genomes are not normally celebrated for being large. But researchers are steadily uncovering algal lineages with big and, in rare cases, enormous plastid DNAs (ptDNAs), such as volvocine green algae. Plastome sequencing of five different volvocine species has revealed some of the largest, most repeat-dense plastomes on record, including that of Volvox carteri (∼525 kb). Volvocine algae have also been used as models for testing leading hypotheses on organelle genome evolution (e.g., the mutational hazard hypothesis), and it has been suggested that ptDNA inflation within this group might be a consequence of low mutation rates and/or the transition from a unicellular to multicellular existence. Here, we further our understanding of plastome size variation in the volvocine line by examining the ptDNA sequences of the colonial species Yamagishiella unicocca and Eudorina sp. NIES-3984 and the multicellular Volvox africanus, which are phylogenetically situated between species with known ptDNA sizes. Although V. africanus is closely related and similar in multicellular organization to V. carteri, its ptDNA was much less inflated than that of V. carteri. Synonymous- and noncoding-site nucleotide substitution rate analyses of these two Volvox ptDNAs suggest that there are drastically different plastid mutation rates operating in the coding versus intergenic regions, supporting the idea that error-prone DNA repair in repeat-rich intergenic spacers is contributing to genome expansion. Our results reinforce the idea that the volvocine line harbors extremes in plastome size but ultimately shed doubt on some of the previously proposed hypotheses for ptDNA inflation within the lineage.}, } @article {pmid30099198, year = {2018}, author = {Lazzari, G and Nicolas, V and Matsusaki, M and Akashi, M and Couvreur, P and Mura, S}, title = {Multicellular spheroid based on a triple co-culture: A novel 3D model to mimic pancreatic tumor complexity.}, journal = {Acta biomaterialia}, volume = {78}, number = {}, pages = {296-307}, doi = {10.1016/j.actbio.2018.08.008}, pmid = {30099198}, issn = {1878-7568}, mesh = {Cell Death ; Cell Line, Tumor ; Cell Survival ; Coculture Techniques ; Fibroblasts/cytology/metabolism ; Human Umbilical Vein Endothelial Cells/cytology/metabolism ; Humans ; *Models, Biological ; Pancreatic Neoplasms/*pathology ; Spheroids, Cellular/*pathology ; Tumor Microenvironment ; }, abstract = {UNLABELLED: The preclinical drug screening of pancreatic cancer treatments suffers from the absence of appropriate models capable to reproduce in vitro the heterogeneous tumor microenvironment and its stiff desmoplasia. Driven by this pressing need, we describe in this paper the conception and the characterization of a novel 3D tumor model consisting of a triple co-culture of pancreatic cancer cells (PANC-1), fibroblasts (MRC-5) and endothelial cells (HUVEC), which assembled to form a hetero-type multicellular tumor spheroid (MCTS). By histological analyses and Selective Plain Illumination Microscopy (SPIM) we have monitored the spatial distribution of each cell type and the evolution of the spheroid composition. Results revealed the presence of a core rich in fibroblasts and fibronectin in which endothelial cells were homogeneously distributed. The integration of the three cell types enabled to reproduce in vitro with fidelity the influence of the surrounding environment on the sensitivity of cancer cells to chemotherapy. To our knowledge, this is the first time that a scaffold-free pancreatic cancer spheroid model combining both tumor and multiple stromal components has been designed. It holds the possibility to become an advantageous tool for a pertinent assessment of the efficacy of various therapeutic strategies.

STATEMENT OF SIGNIFICANCE: Pancreatic tumor microenvironment is characterized by abundant fibrosis and aberrant vasculature. Aiming to reproduce in vitro these features, cancer cells have been already co-cultured with fibroblasts or endothelial cells separately but the integration of both these essential components of the pancreatic tumor microenvironment in a unique system, although urgently needed, was still missing. In this study, we successfully integrated cellular and acellular microenvironment components (i.e., fibroblasts, endothelial cells, fibronectin) in a hetero-type scaffold-free multicellular tumor spheroid. This new 3D triple co-culture model closely mimicked the resistance to treatments observed in vivo, resulting in a reduction of cancer cell sensitivity to the anticancer treatment.}, } @article {pmid30089142, year = {2018}, author = {Tverskoi, D and Makarenkov, V and Aleskerov, F}, title = {Modeling functional specialization of a cell colony under different fecundity and viability rates and resource constraint.}, journal = {PloS one}, volume = {13}, number = {8}, pages = {e0201446}, pmid = {30089142}, issn = {1932-6203}, mesh = {Biological Evolution ; Cell Communication/*physiology ; Cell Differentiation/*physiology ; Cell Survival/physiology ; Chlorophyta/cytology/*physiology ; Fertility/*physiology ; Germ Cells, Plant/physiology ; *Models, Biological ; }, abstract = {The emergence of functional specialization is a core problem in biology. In this work we focus on the emergence of reproductive (germ) and vegetative viability-enhancing (soma) cell functions (or germ-soma specialization). We consider a group of cells and assume that they contribute to two different evolutionary tasks, fecundity and viability. The potential of cells to contribute to fitness components is traded off. As embodied in current models, the curvature of the trade-off between fecundity and viability is concave in small-sized organisms and convex in large-sized multicellular organisms. We present a general mathematical model that explores how the division of labor in a cell colony depends on the trade-off curvatures, a resource constraint and different fecundity and viability rates. Moreover, we consider the case of different trade-off functions for different cells. We describe the set of all possible solutions of the formulated mathematical programming problem and show some interesting examples of optimal specialization strategies found for our objective fitness function. Our results suggest that the transition to specialized organisms can be achieved in several ways. The evolution of Volvocalean green algae is considered to illustrate the application of our model. The proposed model can be generalized to address a number of important biological issues, including the evolution of specialized enzymes and the emergence of complex organs.}, } @article {pmid30086318, year = {2018}, author = {Furumizu, C and Hirakawa, Y and Bowman, JL and Sawa, S}, title = {3D Body Evolution: Adding a New Dimension to Colonize the Land.}, journal = {Current biology : CB}, volume = {28}, number = {15}, pages = {R838-R840}, doi = {10.1016/j.cub.2018.06.040}, pmid = {30086318}, issn = {1879-0445}, mesh = {*Bryopsida ; }, abstract = {Complex multicellular plant bodies evolved in both generations of land plants. A new study demonstrates that CLAVATA3-like peptides function via conserved receptors in Physcomitrella patens as key molecules for morphological innovation of 3D growth in land plants.}, } @article {pmid30082786, year = {2018}, author = {Li, Z and Fu, X and Wang, Y and Liu, R and He, Y}, title = {Polycomb-mediated gene silencing by the BAH-EMF1 complex in plants.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1254-1261}, doi = {10.1038/s41588-018-0190-0}, pmid = {30082786}, issn = {1546-1718}, mesh = {Arabidopsis/genetics ; Arabidopsis Proteins/*genetics ; Chromatin/genetics ; Epigenesis, Genetic/genetics ; Flowers/genetics ; Gene Expression Regulation, Plant/genetics ; Gene Silencing/*physiology ; Genes, Plant/*genetics ; Histones/genetics ; Polycomb Repressive Complex 1/genetics ; Polycomb Repressive Complex 2/genetics ; Polycomb-Group Proteins/*genetics ; }, abstract = {Polycomb proteins implement genome-wide transcriptional repression in multicellular organisms. The evolutionarily conserved Polycomb repressive complex 2 (PRC2) catalyzes histone H3 Lys27 trimethylation (H3K27me3) that is read and effected by Polycomb repressive complex 1 (PRC1) in animals, but the interpretation of this mark remains unclear in plants. Here we report that in the eudicot Arabidopsis thaliana two homologous BAH (Bromo adjacent homology) domain-containing proteins form a plant-specific complex with EMBRYONIC FLOWER 1 (EMF1), and that the BAH-EMF1 complex (BAH-EMF1c) reads and effects the H3K27me3 mark and mediates genome-wide transcriptional repression. Furthermore, in the monocot rice a homolog of the Arabidopsis BAH-domain proteins also binds methylated H3K27 and forms a complex with the rice homolog of EMF1, suggesting that BAH-EMF1c is conserved in flowering plants. Therefore, our results show that the plant-specific BAH-EMF1c fulfills PRC1-like functions in higher plants, suggesting a convergent evolution of PRC1 activity in plants and animals.}, } @article {pmid30082277, year = {2018}, author = {Usui, H and Nishiwaki, A and Landiev, L and Kacza, J and Eichler, W and Wako, R and Kato, A and Takase, N and Kuwayama, S and Ohashi, K and Yafai, Y and Bringmann, A and Kubota, A and Ogura, Y and Seeger, J and Wiedemann, P and Yasukawa, T}, title = {In vitro drusen model - three-dimensional spheroid culture of retinal pigment epithelial cells.}, journal = {Journal of cell science}, volume = {132}, number = {4}, pages = {}, doi = {10.1242/jcs.215798}, pmid = {30082277}, issn = {1477-9137}, mesh = {Amyloid beta-Peptides/metabolism ; Biomarkers/metabolism ; Bruch Membrane/*metabolism ; Epithelial Cells/metabolism ; Humans ; Imaging, Three-Dimensional/methods ; Macular Degeneration/metabolism/pathology ; Retina/*metabolism/pathology ; Retinal Pigment Epithelium/*metabolism/pathology ; Retinal Pigments/*metabolism ; Spheroids, Cellular/metabolism ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in people over 50 years of age in many developed countries. Drusen are yellowish extracellular deposits beneath retinal pigment epithelium (RPE) found in aging eyes and considered as a biomarker of AMD. However, the biogenesis of drusen has not been elucidated. We reported previously that multicellular spheroids of human RPE cells constructed a well-differentiated monolayer of RPE with a Bruch's membrane. We determined that RPE spheroids exhibited drusen formation between the RPE and Bruch's membrane with expression of many drusen-associated proteins, such as amyloid β and complement components, the expression of which was altered by a challenge with oxidative stress. Artificial lipofuscin-loaded RPE spheroids yielded drusen more frequently. In the current study, we showed that drusen originates from the RPE. This culture system is an attractive tool for use as an in vitro drusen model, which might help elucidate the biogenesis of drusen and the pathogenesis of related diseases, such as AMD.}, } @article {pmid30078827, year = {2018}, author = {Oka, M and Yoneda, Y}, title = {Importin α: functions as a nuclear transport factor and beyond.}, journal = {Proceedings of the Japan Academy. Series B, Physical and biological sciences}, volume = {94}, number = {7}, pages = {259-274}, pmid = {30078827}, issn = {1349-2896}, mesh = {Active Transport, Cell Nucleus ; Animals ; Cell Nucleus/*metabolism ; Humans ; Neurons/cytology/metabolism ; Nuclear Pore/metabolism ; alpha Karyopherins/*metabolism ; }, abstract = {Nucleocytoplasmic transport is an essential process in eukaryotes. The molecular mechanisms underlying nuclear transport that involve the nuclear transport receptor, small GTPase Ran, and the nuclear pore complex are highly conserved from yeast to humans. On the other hand, it has become clear that the nuclear transport system diverged during evolution to achieve various physiological functions in multicellular eukaryotes. In this review, we first summarize the molecular mechanisms of nuclear transport and how these were elucidated. Then, we focus on the diverse functions of importin α, which acts not merely an import factor but also as a multi-functional protein contributing to a variety of cellular functions in higher eukaryotes.}, } @article {pmid30072980, year = {2018}, author = {Sharma, G and Burrows, LL and Singer, M}, title = {Diversity and Evolution of Myxobacterial Type IV Pilus Systems.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1630}, pmid = {30072980}, issn = {1664-302X}, abstract = {Type IV pili (T4P) are surface-exposed protein fibers that play key roles in the bacterial life cycle via surface attachment/adhesion, biofilm formation, motility, and development. The order Myxococcales (myxobacteria) are members of the class Deltaproteobacteria and known for their large genome size and complex social behaviors, including gliding motility, fruiting body formation, biofilm production, and prey hunting. Myxococcus xanthus, the best-characterized member of the order, relies on the appropriate expression of 17 type IVa (T4aP) genes organized in a single cluster plus additional genes (distributed throughout the genome) for social motility and development. Here, we compared T4aP genes organization within the myxobacteria to understand their evolutionary origins and diversity. We found that T4aP genes are organized as large clusters in suborder Cystobacterineae, whereas in other two suborders Sorangiineae and Nannocystineae, these genes are dispersed throughout the genome. Based on the genomic organization, the phylogeny of conserved proteins, and synteny studies among 28 myxobacterial and 66 Proteobacterial genomes, we propose an evolutionary model for the origin of myxobacterial T4aP genes independently from other orders in class Deltaproteobacteria. Considering a major role for T4P, this study further proposes the origins and evolution of social motility in myxobacteria and provides a foundation for understanding how complex-behavioral traits, such as gliding motility, multicellular development, etc., might have evolved in this diverse group of complex organisms.}, } @article {pmid30068565, year = {2018}, author = {Bornens, M}, title = {Cell polarity: having and making sense of direction-on the evolutionary significance of the primary cilium/centrosome organ in Metazoa.}, journal = {Open biology}, volume = {8}, number = {8}, pages = {}, pmid = {30068565}, issn = {2046-2441}, mesh = {Animals ; Biological Evolution ; Cell Movement ; Cell Polarity ; Centrosome/*metabolism ; Cilia/*metabolism ; Planarians/*physiology ; }, abstract = {Cell-autonomous polarity in Metazoans is evolutionarily conserved. I assume that permanent polarity in unicellular eukaryotes is required for cell motion and sensory reception, integration of these two activities being an evolutionarily constrained function. Metazoans are unique in making cohesive multicellular organisms through complete cell divisions. They evolved a primary cilium/centrosome (PC/C) organ, ensuring similar functions to the basal body/flagellum of unicellular eukaryotes, but in different cells, or in the same cell at different moments. The possibility that this innovation contributed to the evolution of individuality, in being instrumental in the early specification of the germ line during development, is further discussed. Then, using the example of highly regenerative organisms like planarians, which have lost PC/C organ in dividing cells, I discuss the possibility that part of the remodelling necessary to reach a new higher-level unit of selection in multi-cellular organisms has been triggered by conflicts among individual cell polarities to reach an organismic polarity. Finally, I briefly consider organisms with a sensorimotor organ like the brain that requires exceedingly elongated polarized cells for its activity. I conclude that beyond critical consequences for embryo development, the conservation of cell-autonomous polarity in Metazoans had far-reaching implications for the evolution of individuality.}, } @article {pmid30066215, year = {2018}, author = {Stencel, A and Wloch-Salamon, DM}, title = {Some theoretical insights into the hologenome theory of evolution and the role of microbes in speciation.}, journal = {Theory in biosciences = Theorie in den Biowissenschaften}, volume = {137}, number = {2}, pages = {197-206}, pmid = {30066215}, issn = {1611-7530}, support = {2018/28/T/HS1/00201//Narodowe Centrum Nauki/ ; Opus 2017/25/B/NZ8/01035//Narodowe Centrum Nauki/ ; DS/762 - K/ZDS/007338//Uniwersytet Jagielloński w Krakowie/ ; }, mesh = {*Adaptation, Biological ; Adaptation, Physiological/genetics ; Animals ; *Genetic Speciation ; Host-Parasite Interactions/genetics ; Microbiota ; Philosophy ; Plants ; Species Specificity ; *Symbiosis ; }, abstract = {Research on symbiotic communities (microbiomes) of multicellular organisms seems to be changing our understanding of how species of plants and animals have evolved over millions of years. The quintessence of these discoveries is the emergence of the hologenome theory of evolution, founded on the concept that a holobiont (a host along with all of its associated symbiotic microorganisms) acts a single unit of selection in the process of evolution. Although the hologenome theory has become very popular among certain scientific circles, its principles are still being debated. In this paper, we argue, firstly, that only a very small number of symbiotic microorganisms are sufficiently integrated into multicellular organisms to act in concert with them as units of selection, thus rendering claims that holobionts are units of selection invalid. Secondly, even though holobionts are not units of selection, they can still constitute genuine units from an evolutionary perspective, provided we accept certain constraints: mainly, they should be considered units of co-operation. Thirdly, we propose a reconciliation of the role of symbiotic microorganisms with the theory of speciation through the use of a developed framework. Mainly, we will argue that, in order to understand the role of microorganisms in the speciation of multicellular organisms, it is not necessary to consider holobionts units of selection; it is sufficient to consider them units of co-operation.}, } @article {pmid30065707, year = {2018}, author = {Chen, H and Zhang, SD and Chen, L and Cai, Y and Zhang, WJ and Song, T and Wu, LF}, title = {Efficient Genome Editing of Magnetospirillum magneticum AMB-1 by CRISPR-Cas9 System for Analyzing Magnetotactic Behavior.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1569}, pmid = {30065707}, issn = {1664-302X}, abstract = {Magnetotactic bacteria (MTB) are a diverse group of microorganisms capable of using geomagnetic fields for navigation. This magnetotactic behavior can help microorganisms move toward favorable habitats for optimal growth and reproduction. A comprehensive understanding of the magnetotactic mechanism at molecular levels requires highly efficient genomic editing tools, which remain underdeveloped in MTB. Here, we adapted an engineered CRISPR-Cas9 system for efficient inactivation of genes in a widely used MTB model strain, Magnetospirillum magneticum AMB-1. By combining a nuclease-deficient Cas9 (dCas9) and single-guide RNA (sgRNA), a CRISPR interference system was successfully developed to repress amb0994 expression. Furthermore, we constructed an in-frame deletion mutant of amb0994 by developing a CRISPR-Cas9 system. This mutant produces normal magnetosomes; however, its response to abrupt magnetic field reversals is faster than wild-type strain. This behavioral difference is probably a consequence of altered flagella function, as suggested with our dynamics simulation study by modeling M. magneticum AMB-1 cell as an ellipsoid. These data indicate that, Amb0994 is involved in the cellular response to magnetic torque changes via controlling flagella. In summary, this study, besides contributing to a better understanding of magnetotaxis mechanism, demonstrated the CRISPR-(d)Cas9 system as a useful genetic tool for efficient genome editing in MTB.}, } @article {pmid30061903, year = {2018}, author = {Benítez, M and Hernández-Hernández, V and Newman, SA and Niklas, KJ}, title = {Dynamical Patterning Modules, Biogeneric Materials, and the Evolution of Multicellular Plants.}, journal = {Frontiers in plant science}, volume = {9}, number = {}, pages = {871}, pmid = {30061903}, issn = {1664-462X}, abstract = {Comparative analyses of developmental processes across a broad spectrum of organisms are required to fully understand the mechanisms responsible for the major evolutionary transitions among eukaryotic photosynthetic lineages (defined here as the polyphyletic algae and the monophyletic land plants). The concepts of dynamical patterning modules (DPMs) and biogeneric materials provide a framework for studying developmental processes in the context of such comparative analyses. In the context of multicellularity, DPMs are defined as sets of conserved gene products and molecular networks, in conjunction with the physical morphogenetic and patterning processes they mobilize. A biogeneric material is defined as mesoscale matter with predictable morphogenetic capabilities that arise from complex cellular conglomerates. Using these concepts, we outline some of the main events and transitions in plant evolution, and describe the DPMs and biogeneric properties associated with and responsible for these transitions. We identify four primary DPMs that played critical roles in the evolution of multicellularity (i.e., the DPMs responsible for cell-to-cell adhesion, identifying the future cell wall, cell differentiation, and cell polarity). Three important conclusions emerge from a broad phyletic comparison: (1) DPMs have been achieved in different ways, even within the same clade (e.g., phycoplastic cell division in the Chlorophyta and phragmoplastic cell division in the Streptophyta), (2) DPMs had their origins in the co-option of molecular species present in the unicellular ancestors of multicellular plants, and (3) symplastic transport mediated by intercellular connections, particularly plasmodesmata, was critical for the evolution of complex multicellularity in plants.}, } @article {pmid30061561, year = {2018}, author = {Stewart, AD and Rice, WR}, title = {Arrest of sex-specific adaptation during the evolution of sexual dimorphism in Drosophila.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1507-1513}, doi = {10.1038/s41559-018-0613-4}, pmid = {30061561}, issn = {2397-334X}, support = {1R01HD057974-01/NH/NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; *Body Size ; Drosophila melanogaster/*anatomy & histology ; Female ; Male ; *Sex Characteristics ; }, abstract = {Sexually antagonistic selection arises when a trait expressed in both sexes (a shared trait) is selected towards different, sex-specific optima. Sex-discordant selection causes different alleles to be favoured in each sex (intralocus sexual conflict). A key parameter responsible for generating this conflict is the intersexual genetic correlation (rMF), which determines the degree to which heritable genetic variation for the shared trait produces a similar phenotype in both sexes. A strong, positive rMF interferes with adaptation when there is sex-discordant selection. In principle, the rMF can evolve in response to sex-discordant selection: the faster it declines, the faster the resolution of intralocus sexual conflict. Here, we use Drosophila melanogaster to quantify the time scale over which a strong, positive rMF impedes a response to sex-discordant selection for a canonical quantitative trait (body size) with an exceptionally long (250 generations) selection experiment for a complex multicellular organism. We found that, compared with rapid and substantial evolution under sex-concordant selection, a high rMF arrested sex-specific adaptation for 100 generations in females and a minimum of 250 generations in males. Our study demonstrates that a high rMF can lead to a protracted period of adaptive stalemate during the evolution of sexual dimorphism.}, } @article {pmid30061406, year = {2018}, author = {Dunn, BS and Rush, L and Lu, JY and Xu, T}, title = {Mutations in the Drosophila tricellular junction protein M6 synergize with Ras[V12] to induce apical cell delamination and invasion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8358-8363}, pmid = {30061406}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Cell Movement ; Drosophila Proteins/genetics/*physiology ; Drosophila melanogaster/genetics ; Intercellular Junctions/*physiology ; *Mutation ; Myosin Type II/physiology ; *Neoplasm Invasiveness ; Neoplasm Metastasis ; ras Proteins/*physiology ; rhoA GTP-Binding Protein/physiology ; }, abstract = {Complications from metastasis are responsible for the majority of cancer-related deaths. Despite the outsized medical impact of metastasis, remarkably little is known about one of the key early steps of metastasis: departure of a tumor cell from its originating tissue. It is well documented that cellular delamination in the basal direction can induce invasive behaviors, but it remains unknown if apical cell delamination can induce migration and invasion in a cancer context. To explore this feature of cancer progression, we performed a genetic screen in Drosophila and discovered that mutations in the protein M6 synergize with oncogenic Ras to drive invasion following apical delamination without crossing a basement membrane. Mechanistically, we observed that M6-deficient Ras[V12] clones delaminate as a result of alterations in a Canoe-RhoA-myosin II axis that is necessary for both the delamination and invasion phenotypes. To uncover the cellular roles of M6, we show that it localizes to tricellular junctions in epithelial tissues where it is necessary for the structural integrity of multicellular contacts. This work provides evidence that apical delamination can precede invasion and highlights the important role that tricellular junction integrity can play in this process.}, } @article {pmid30059538, year = {2018}, author = {Waldron, FM and Stone, GN and Obbard, DJ}, title = {Metagenomic sequencing suggests a diversity of RNA interference-like responses to viruses across multicellular eukaryotes.}, journal = {PLoS genetics}, volume = {14}, number = {7}, pages = {e1007533}, pmid = {30059538}, issn = {1553-7404}, support = {WT095831//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Annelida/genetics/immunology/microbiology ; Argonaute Proteins/genetics ; Cnidaria/genetics/immunology/microbiology ; DNA Transposable Elements/genetics ; Echinodermata/genetics/immunology/microbiology ; Host Microbial Interactions/*genetics/immunology ; *Metagenomics ; Mollusca/genetics/immunology/microbiology ; Phaeophyta/genetics/immunology/microbiology ; Phylogeny ; Porifera/genetics/immunology/microbiology ; RNA Interference/*immunology ; RNA Viruses/genetics/*immunology ; RNA, Small Interfering/genetics/metabolism ; RNA, Viral/*genetics/immunology ; Ribonuclease III/genetics ; Sequence Analysis, RNA ; }, abstract = {RNA interference (RNAi)-related pathways target viruses and transposable element (TE) transcripts in plants, fungi, and ecdysozoans (nematodes and arthropods), giving protection against infection and transmission. In each case, this produces abundant TE and virus-derived 20-30nt small RNAs, which provide a characteristic signature of RNAi-mediated defence. The broad phylogenetic distribution of the Argonaute and Dicer-family genes that mediate these pathways suggests that defensive RNAi is ancient, and probably shared by most animal (metazoan) phyla. Indeed, while vertebrates had been thought an exception, it has recently been argued that mammals also possess an antiviral RNAi pathway, although its immunological relevance is currently uncertain and the viral small RNAs (viRNAs) are not easily detectable. Here we use a metagenomic approach to test for the presence of viRNAs in five species from divergent animal phyla (Porifera, Cnidaria, Echinodermata, Mollusca, and Annelida), and in a brown alga-which represents an independent origin of multicellularity from plants, fungi, and animals. We use metagenomic RNA sequencing to identify around 80 virus-like contigs in these lineages, and small RNA sequencing to identify viRNAs derived from those viruses. We identified 21U small RNAs derived from an RNA virus in the brown alga, reminiscent of plant and fungal viRNAs, despite the deep divergence between these lineages. However, contrary to our expectations, we were unable to identify canonical (i.e. Drosophila- or nematode-like) viRNAs in any of the animals, despite the widespread presence of abundant micro-RNAs, and somatic transposon-derived piwi-interacting RNAs. We did identify a distinctive group of small RNAs derived from RNA viruses in the mollusc. However, unlike ecdysozoan viRNAs, these had a piRNA-like length distribution but lacked key signatures of piRNA biogenesis. We also identified primary piRNAs derived from putatively endogenous copies of DNA viruses in the cnidarian and the echinoderm, and an endogenous RNA virus in the mollusc. The absence of canonical virus-derived small RNAs from our samples may suggest that the majority of animal phyla lack an antiviral RNAi response. Alternatively, these phyla could possess an antiviral RNAi response resembling that reported for vertebrates, with cryptic viRNAs not detectable through simple metagenomic sequencing of wild-type individuals. In either case, our findings show that the antiviral RNAi responses of arthropods and nematodes, which are highly divergent from each other and from that of plants and fungi, are also highly diverged from the most likely ancestral metazoan state.}, } @article {pmid30033369, year = {2018}, author = {Glass, DS and Riedel-Kruse, IH}, title = {A Synthetic Bacterial Cell-Cell Adhesion Toolbox for Programming Multicellular Morphologies and Patterns.}, journal = {Cell}, volume = {174}, number = {3}, pages = {649-658.e16}, doi = {10.1016/j.cell.2018.06.041}, pmid = {30033369}, issn = {1097-4172}, mesh = {Bacterial Physiological Phenomena ; Biological Evolution ; Cell Adhesion/genetics/*physiology ; Cell Differentiation/genetics/physiology ; Escherichia coli/genetics ; Gene Library ; Metabolic Engineering/*methods ; Metabolic Networks and Pathways ; Single-Domain Antibodies/genetics/immunology/physiology ; Synthetic Biology/*methods ; }, abstract = {Synthetic multicellular systems hold promise as models for understanding natural development of biofilms and higher organisms and as tools for engineering complex multi-component metabolic pathways and materials. However, such efforts require tools to adhere cells into defined morphologies and patterns, and these tools are currently lacking. Here, we report a 100% genetically encoded synthetic platform for modular cell-cell adhesion in Escherichia coli, which provides control over multicellular self-assembly. Adhesive selectivity is provided by a library of outer membrane-displayed nanobodies and antigens with orthogonal intra-library specificities, while affinity is controlled by intrinsic adhesin affinity, competitive inhibition, and inducible expression. We demonstrate the resulting capabilities for quantitative rational design of well-defined morphologies and patterns through homophilic and heterophilic interactions, lattice-like self-assembly, phase separation, differential adhesion, and sequential layering. Compatible with synthetic biology standards, this adhesion toolbox will enable construction of high-level multicellular designs and shed light on the evolutionary transition to multicellularity.}, } @article {pmid30028958, year = {2018}, author = {Campbell, FC and Loughrey, MB and McClements, J and Deevi, RK and Javadi, A and Rainey, L}, title = {Mechanistic Insights into Colorectal Cancer Phenomics from Fundamental and Organotypic Model Studies.}, journal = {The American journal of pathology}, volume = {188}, number = {9}, pages = {1936-1948}, pmid = {30028958}, issn = {1525-2191}, support = {C9136/A15342//Cancer Research UK/United Kingdom ; MR/L015110/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Colorectal Neoplasms/*pathology ; *Disease Models, Animal ; Humans ; Organ Culture Techniques/*methods ; }, abstract = {Colorectal cancer (CRC) diagnosis and prognostic stratification are based on histopathologic assessment of cell or nuclear pleomorphism, aberrant mitotic figures, altered glandular architecture, and other phenomic abnormalities. This complexity is driven by oncogenic perturbation of tightly coordinated spatiotemporal signaling to disrupt multiple scales of tissue organization. This review clarifies molecular and cellular mechanisms underlying common CRC histologic features and helps understand how the CRC genome controls core aspects of tumor aggressiveness. It further explores a spatiotemporal framework for CRC phenomics based on regulation of living cells in fundamental and organotypic model systems. The review also discusses tissue homeostasis, considers distinct classes of oncogenic perturbations, and evolution of cellular or multicellular cancer phenotypes. It further explores the molecular controls of cribriform, micropapillary, and high-grade CRC morphology in organotypic culture models and assesses relevant translational studies. In addition, the review delves into complexities of morphologic plasticity whereby a single molecular signature generates heterogeneous cancer phenotypes, and, conversely, morphologically homogeneous tumors show substantive molecular diversity. Principles outlined may aid mechanistic interpretation of omics data in a setting of cancer pathology, provide insight into CRC consensus molecular subtypes, and better define principles for CRC prognostic stratification.}, } @article {pmid29995583, year = {2019}, author = {Hou, S and Brenes-Álvarez, M and Reimann, V and Alkhnbashi, OS and Backofen, R and Muro-Pastor, AM and Hess, WR}, title = {CRISPR-Cas systems in multicellular cyanobacteria.}, journal = {RNA biology}, volume = {16}, number = {4}, pages = {518-529}, pmid = {29995583}, issn = {1555-8584}, mesh = {Base Sequence ; CRISPR-Cas Systems/*genetics ; Cell Differentiation/genetics ; Cyanobacteria/*cytology/*genetics ; Gene Expression Regulation, Bacterial ; Homologous Recombination/genetics ; Phylogeny ; Synteny/genetics ; }, abstract = {Novel CRISPR-Cas systems possess substantial potential for genome editing and manipulation of gene expression. The types and numbers of CRISPR-Cas systems vary substantially between different organisms. Some filamentous cyanobacteria harbor > 40 different putative CRISPR repeat-spacer cassettes, while the number of cas gene instances is much lower. Here we addressed the types and diversity of CRISPR-Cas systems and of CRISPR-like repeat-spacer arrays in 171 publicly available genomes of multicellular cyanobacteria. The number of 1328 repeat-spacer arrays exceeded the total of 391 encoded Cas1 proteins suggesting a tendency for fragmentation or the involvement of alternative adaptation factors. The model cyanobacterium Anabaena sp. PCC 7120 contains only three cas1 genes but hosts three Class 1, possibly one Class 2 and five orphan repeat-spacer arrays, all of which exhibit crRNA-typical expression patterns suggesting active transcription, maturation and incorporation into CRISPR complexes. The CRISPR-Cas system within the element interrupting the Anabaena sp. PCC 7120 fdxN gene, as well as analogous arrangements in other strains, occupy the genetic elements that become excised during the differentiation-related programmed site-specific recombination. This fact indicates the propensity of these elements for the integration of CRISPR-cas systems and points to a previously not recognized connection. The gene all3613 resembling a possible Class 2 effector protein is linked to a short repeat-spacer array and a single tRNA gene, similar to its homologs in other cyanobacteria. The diversity and presence of numerous CRISPR-Cas systems in DNA elements that are programmed for homologous recombination make filamentous cyanobacteria a prolific resource for their study. Abbreviations: Cas: CRISPR associated sequences; CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats; C2c: Class 2 candidate; SDR: small dispersed repeat; TSS: transcriptional start site; UTR: untranslated region.}, } @article {pmid29992410, year = {2018}, author = {Leong, SP and Aktipis, A and Maley, C}, title = {Cancer initiation and progression within the cancer microenvironment.}, journal = {Clinical & experimental metastasis}, volume = {35}, number = {5-6}, pages = {361-367}, pmid = {29992410}, issn = {1573-7276}, mesh = {Carcinogenesis/*genetics ; Cell Proliferation/*genetics ; Disease Progression ; Humans ; Melanoma/*genetics/pathology ; Neoplasm Metastasis ; Tumor Microenvironment/*genetics ; }, abstract = {Within the cancer microenvironment, the growth and proliferation of cancer cells in the primary site as well as in the metastatic site represent a global biological phenomenon. To understand the growth, proliferation and progression of cancer either by local expansion and/or metastasis, it is important to understand the cancer microenvironment and host response to cancer growth. Melanoma is an excellent model to study the interaction of cancer initiation and growth in relationship to its microenvironment. Social evolution with cooperative cellular groups within an organism is what gives rise to multicellularity in the first place. Cancer cells evolve to exploit their cellular environment. The foundations of multicellular cooperation break down in cancer because those cells that misbehave have an evolutionary advantage over their normally behaving neighbors. It is important to classify evolutionary and ecological aspects of cancer growth, thus, data for cancer growth and outcomes need to be collected to define these parameters so that accurate predictions of how cancer cells may proliferate and metastasize can be developed.}, } @article {pmid29981215, year = {2018}, author = {Chang, J and Yu, T and Yang, Q and Li, C and Xiong, C and Gao, S and Xie, Q and Zheng, F and Li, H and Tian, Z and Yang, C and Ye, Z}, title = {Hair, encoding a single C2H2 zinc-finger protein, regulates multicellular trichome formation in tomato.}, journal = {The Plant journal : for cell and molecular biology}, volume = {96}, number = {1}, pages = {90-102}, doi = {10.1111/tpj.14018}, pmid = {29981215}, issn = {1365-313X}, mesh = {Alleles ; CYS2-HIS2 Zinc Fingers/*physiology ; Capsicum ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Genome-Wide Association Study ; Solanum lycopersicum/genetics/growth & development/*metabolism ; Plant Proteins/genetics/*physiology ; Plants, Genetically Modified ; Tobacco ; Trichomes/*growth & development ; Two-Hybrid System Techniques ; }, abstract = {Trichomes originate from the epidermal cells of nearly all terrestrial plants, which are specialized unicellular or multicellular structures. Although the molecular mechanism regulating unicellular trichome formation has been extensively characterized, most of the genes essential for multicellular trichome formation remain unknown. In this study, we identified an associated locus on the long arm of chromosome 10 using a genome-wide association study (GWAS) on type-I trichomes of 180 diverse Solanum lycopersicum (tomato) accessions. Using map-based cloning we then cloned the key gene controlling the initiation of this type of trichome, named Hair (H), which encodes a single C2H2 zinc-finger protein. Transgenic experiments showed that hair-absent phenotype is caused by the deletion of the entire coding region of H. We identified three alleles of H containing several missense mutations and a nucleotide deletion, which result in amino acid substitutions and a reading frame shift, respectively. In addition, knockdown of H or Woolly (Wo) represses the formation of type-I trichomes, suggesting that both regulators may function as a heterodimer. Direct protein-protein interaction between them was further detected through pull-down and yeast two-hybrid assays. In addition, ectopic expression of H in Nicotiana tabacum (tobacco) and expression of its homologs from Capsicum annuum (pepper) and tobacco in tomato can trigger trichome formation. Taken together, these findings suggest that the H gene may be functionally conserved in multicellular trichome formation in Solanaceae species.}, } @article {pmid29966484, year = {2018}, author = {Liao, Z and Kjellin, J and Hoeppner, MP and Grabherr, M and Söderbom, F}, title = {Global characterization of the Dicer-like protein DrnB roles in miRNA biogenesis in the social amoeba Dictyostelium discoideum.}, journal = {RNA biology}, volume = {15}, number = {7}, pages = {937-954}, pmid = {29966484}, issn = {1555-8584}, mesh = {Adaptation, Biological ; Biological Evolution ; Dictyostelium/genetics/*metabolism ; Gene Knockout Techniques ; Genome, Protozoan/genetics ; High-Throughput Nucleotide Sequencing ; MicroRNAs/analysis/*biosynthesis/genetics ; Oligonucleotide Probes/analysis/genetics/metabolism ; Promoter Regions, Genetic/genetics ; Protozoan Proteins/genetics/*metabolism ; RNA, Protozoan/analysis/*biosynthesis/genetics ; Ribonuclease III/genetics/*metabolism ; Transcription, Genetic ; }, abstract = {Micro (mi)RNAs regulate gene expression in many eukaryotic organisms where they control diverse biological processes. Their biogenesis, from primary transcripts to mature miRNAs, have been extensively characterized in animals and plants, showing distinct differences between these phylogenetically distant groups of organisms. However, comparably little is known about miRNA biogenesis in organisms whose evolutionary position is placed in between plants and animals and/or in unicellular organisms. Here, we investigate miRNA maturation in the unicellular amoeba Dictyostelium discoideum, belonging to Amoebozoa, which branched out after plants but before animals. High-throughput sequencing of small RNAs and poly(A)-selected RNAs demonstrated that the Dicer-like protein DrnB is required, and essentially specific, for global miRNA maturation in D. discoideum. Our RNA-seq data also showed that longer miRNA transcripts, generally preceded by a T-rich putative promoter motif, accumulate in a drnB knock-out strain. For two model miRNAs we defined the transcriptional start sites (TSSs) of primary (pri)-miRNAs and showed that they carry the RNA polymerase II specific m[7]G-cap. The generation of the 3'-ends of these pri-miRNAs differs, with pri-mir-1177 reading into the downstream gene, and pri-mir-1176 displaying a distinct end. This 3´-end is processed to shorter intermediates, stabilized in DrnB-depleted cells, of which some carry a short oligo(A)-tail. Furthermore, we identified 10 new miRNAs, all DrnB dependent and developmentally regulated. Thus, the miRNA machinery in D. discoideum shares features with both plants and animals, which is in agreement with its evolutionary position and perhaps also an adaptation to its complex lifestyle: unicellular growth and multicellular development.}, } @article {pmid29961831, year = {2018}, author = {Zhao, J and Yuan, S and Gao, B and Zhu, S}, title = {Molecular diversity of fungal inhibitor cystine knot peptides evolved by domain repeat and fusion.}, journal = {FEMS microbiology letters}, volume = {365}, number = {15}, pages = {}, doi = {10.1093/femsle/fny158}, pmid = {29961831}, issn = {1574-6968}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Evolution, Molecular ; Exons ; Fungal Proteins/chemistry/genetics/metabolism ; Fungi/chemistry/classification/*genetics/metabolism ; Genetic Variation ; Genome, Fungal ; Introns ; Peptides/*chemistry/*genetics/metabolism ; Phylogeny ; Protein Domains ; Sequence Alignment ; }, abstract = {Peptides with the inhibitor cystine knot (ICK) motif are extensively present in animals and plants where they exert a diversity of biological functions. However, few studies have been undertaken on this class of peptides in fungi. In this work, we identify a total of 386 fungal ICK peptides and proteins containing this motif by computational data mining of fungal genome databases, which exhibit 14 different exon-intron structures. According to their domain architectures, these proteins are classified into three distinct structural types, including single domains, tandem repeat domains and fusion domains, in which six families belonging to single or tandem repeat domains show remarkable sequence similarity to those from animals and plants, suggesting their orthologous relationship. Extremely high molecular diversity in fungal ICKs might be attributable to different genetic mechanisms, such as gene/domain duplication and fusion. This work not only enlarges the number of ICK peptides in multicellular organisms, but also uncovers their complex evolutionary history in a specific lineage.}, } @article {pmid29954963, year = {2018}, author = {Pennisi, E}, title = {Is cancer a breakdown of multicellularity?.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1391}, doi = {10.1126/science.360.6396.1391}, pmid = {29954963}, issn = {1095-9203}, mesh = {*Biological Evolution ; Carcinogenesis/genetics/*pathology ; Gene Regulatory Networks ; Humans ; Neoplasms/genetics/*pathology ; }, } @article {pmid29942020, year = {2018}, author = {Sebé-Pedrós, A and Chomsky, E and Pang, K and Lara-Astiaso, D and Gaiti, F and Mukamel, Z and Amit, I and Hejnol, A and Degnan, BM and Tanay, A}, title = {Early metazoan cell type diversity and the evolution of multicellular gene regulation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1176-1188}, pmid = {29942020}, issn = {2397-334X}, support = {309706/ERC_/European Research Council/International ; }, mesh = {Animals ; *Biological Evolution ; Ctenophora/*cytology/genetics ; Placozoa/*cytology/genetics ; Porifera/*cytology/genetics ; Sequence Analysis, RNA ; Transcription, Genetic/*physiology ; }, abstract = {A hallmark of metazoan evolution is the emergence of genomic mechanisms that implement cell-type-specific functions. However, the evolution of metazoan cell types and their underlying gene regulatory programmes remains largely uncharacterized. Here, we use whole-organism single-cell RNA sequencing to map cell-type-specific transcription in Porifera (sponges), Ctenophora (comb jellies) and Placozoa species. We describe the repertoires of cell types in these non-bilaterian animals, uncovering diverse instances of previously unknown molecular signatures, such as multiple types of peptidergic cells in Placozoa. Analysis of the regulatory programmes of these cell types reveals variable levels of complexity. In placozoans and poriferans, sequence motifs in the promoters are predictive of cell-type-specific programmes. By contrast, the generation of a higher diversity of cell types in ctenophores is associated with lower specificity of promoter sequences and the existence of distal regulatory elements. Our findings demonstrate that metazoan cell types can be defined by networks of transcription factors and proximal promoters, and indicate that further genome regulatory complexity may be required for more diverse cell type repertoires.}, } @article {pmid29939836, year = {2018}, author = {Pashov, A and Hernandez Puente, CV and Ibrahim, SM and Monzavi-Karbassi, B and Makhoul, I and Kieber-Emmons, T}, title = {Thinking Cancer.}, journal = {Monoclonal antibodies in immunodiagnosis and immunotherapy}, volume = {37}, number = {3}, pages = {117-125}, doi = {10.1089/mab.2018.0014}, pmid = {29939836}, issn = {2167-9436}, mesh = {Animals ; Anthroposophy ; Autoantibodies/biosynthesis/genetics ; B7-H1 Antigen/*genetics/immunology ; Cell Transformation, Neoplastic/*genetics/immunology/pathology ; *Epigenesis, Genetic ; *Gene Expression Regulation, Neoplastic ; Gene-Environment Interaction ; Homeostasis/genetics/immunology ; Humans ; Immunity, Innate ; Interferon-gamma/genetics/immunology ; Mutation ; Neoplasm Proteins/*genetics/immunology ; Neoplasms/*genetics/immunology/pathology ; }, abstract = {Evolutionary theories are necessarily invoked for understanding cancer development at the level of species, at the level of cells and tissues, and for developing effective therapies. It is crucial to view cancer in a Darwinian light, where the differential survival of individual cells is based on heritable variations. In the process of this somatic evolution, multicellularity controls are overridden by cancer cells, which become increasingly autonomous. Ecological epigenetics also helps understand how rogue cells that have basically the same DNA as their normal cell counterpart overcome the tissue homeostasis. As we struggle to wrap our minds around the complexity of these phenomena, we apply often times anthropomorphic terms, such as subversion, hijacking, or hacking, to describe especially the most complex among them-the interaction of tumors with the immune system. In this commentary we highlight examples of the anthropomorphic thinking of cancer and try to put into context the relative meaning of terms and the mechanisms that are oftentimes invoked to justify those terms.}, } @article {pmid29938763, year = {2018}, author = {Funayama, N}, title = {The cellular and molecular bases of the sponge stem cell systems underlying reproduction, homeostasis and regeneration.}, journal = {The International journal of developmental biology}, volume = {62}, number = {6-7-8}, pages = {513-525}, doi = {10.1387/ijdb.180016nf}, pmid = {29938763}, issn = {1696-3547}, mesh = {Animals ; Cell Differentiation/genetics/physiology ; Cell Plasticity/genetics/physiology ; Cell Transdifferentiation/genetics/physiology ; Gene Expression Profiling ; Homeostasis/genetics/*physiology ; Porifera/cytology/genetics/*physiology ; Regeneration/genetics/*physiology ; Reproduction/genetics/physiology ; Stem Cells/cytology/metabolism/*physiology ; }, abstract = {The evolution of multicellular organisms is generally thought (and seems likely) to have been accompanied by the evolution of a stem cell system. Sponges, some of the early-evolved metazoans, have totipotent/pluripotent stem cells. Thus, uncovering the cellular and molecular bases of the sponge stem cells will not only be crucial for understanding the ancestral gene repertoire of animal stem cells, but will also give us clues to understanding the evolution of molecular mechanisms for maintaining multipotency (pluripotency) and differentiation ability during animal evolution. Sponges (Porifera) are a large phylum that includes an enormous number of species, whose cellular compositions and life cycles show striking variations. In the last decade, methodologies for molecular studies and sequencing resources have dramatically advanced and made it possible to clearly define stem cells in sponges in cellular and molecular terms. In this review, together with recent studies of sponges in various classes, the following issues will be discussed: i) recent findings that revealed that the previously proposed model that "archeocytes and choanocytes are the two types of stem cells" originally based on work in demosponges can be applied as a unified view of the stem cell system in sponges that have various cellular organizations, ii) the fact that sponge cells are more plastic than previously thought, as shown by recent studies of sponge regeneration both from dissociated cells and upon injury, and iii) the importance of transdifferentiation in sponge stem cell systems and regeneration.}, } @article {pmid29930939, year = {2018}, author = {Fiore, APZP and Ribeiro, PF and Bruni-Cardoso, A}, title = {Sleeping Beauty and the Microenvironment Enchantment: Microenvironmental Regulation of the Proliferation-Quiescence Decision in Normal Tissues and in Cancer Development.}, journal = {Frontiers in cell and developmental biology}, volume = {6}, number = {}, pages = {59}, pmid = {29930939}, issn = {2296-634X}, abstract = {Cells from prokaryota to the more complex metazoans cease proliferating at some point in their lives and enter a reversible, proliferative-dormant state termed quiescence. The appearance of quiescence in the course of evolution was essential to the acquisition of multicellular specialization and compartmentalization and is also a central aspect of tissue function and homeostasis. But what makes a cell cease proliferating even in the presence of nutrients, growth factors, and mitogens? And what makes some cells "wake up" when they should not, as is the case in cancer? Here, we summarize and discuss evidence showing how microenvironmental cues such as those originating from metabolism, extracellular matrix (ECM) composition and arrangement, neighboring cells and tissue architecture control the cellular proliferation-quiescence decision, and how this complex regulation is corrupted in cancer.}, } @article {pmid29914363, year = {2018}, author = {Dunning Hotopp, JC}, title = {Grafting or pruning in the animal tree: lateral gene transfer and gene loss?.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {470}, pmid = {29914363}, issn = {1471-2164}, support = {R01 CA206188/CA/NCI NIH HHS/United States ; ABI-1457957//National Science Foundation/ ; 1-R01-CA206188//National Cancer Institute/ ; }, mesh = {Animals ; Bacteria/*genetics ; Eukaryota/*genetics ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genome ; Humans ; Phylogeny ; Prokaryotic Cells/*metabolism ; }, abstract = {BACKGROUND: Lateral gene transfer (LGT), also known as horizontal gene transfer, into multicellular eukaryotes with differentiated tissues, particularly gonads, continues to be met with skepticism by many prominent evolutionary and genomic biologists. A detailed examination of 26 animal genomes identified putative LGTs in invertebrate and vertebrate genomes, concluding that there are fewer predicted LGTs in vertebrates/chordates than invertebrates, but there is still evidence of LGT into chordates, including humans. More recently, a reanalysis of a subset of these putative LGTs into vertebrates concluded that there is not horizontal gene transfer in the human genome. One of the genes in dispute is an N-acyl-aromatic-L-amino acid amidohydrolase (ENSG00000132744), which encodes ACY3. This gene was initially identified as a putative bacteria-chordate LGT but was later debunked as it has a significant BLAST match to a more recently deposited genome of Saccoglossus kowalevskii, a flatworm, Metazoan, and hemichordate.

RESULTS: Using BLAST searches, HMM searches, and phylogenetics to assess the evidence for LGT, gene loss, and rate variation in ACY3/ASPA homologues, the most parsimonious explanation for the distribution of ACY3/ASPA genes in eukaryotes involves both gene loss and bacteria-animal LGT, albeit LGT that occurred hundreds of millions of years ago prior to the divergence of gnathostomes.

CONCLUSIONS: ACY3/ASPA is most likely a bacteria-animal LGT. LGTs at these time scales in the ancestors of humans are not unexpected given the many known, well-characterized, and adaptive LGTs from bacteria to insects and nematodes.}, } @article {pmid29906914, year = {2018}, author = {Kang, C and Aguilar, B and Shmulevich, I}, title = {Emergence of diversity in homogeneous coupled Boolean networks.}, journal = {Physical review. E}, volume = {97}, number = {5-1}, pages = {052415}, doi = {10.1103/PhysRevE.97.052415}, pmid = {29906914}, issn = {2470-0053}, mesh = {Evolution, Molecular ; *Gene Regulatory Networks ; *Models, Genetic ; }, abstract = {The origin of multicellularity in metazoa is one of the fundamental questions of evolutionary biology. We have modeled the generic behaviors of gene regulatory networks in isogenic cells as stochastic nonlinear dynamical systems-coupled Boolean networks with perturbation. Model simulations under a variety of dynamical regimes suggest that the central characteristic of multicellularity, permanent spatial differentiation (diversification), indeed can arise. Additionally, we observe that diversification is more likely to occur near the critical regime of Lyapunov stability.}, } @article {pmid29906891, year = {2018}, author = {Jacobeen, S and Graba, EC and Brandys, CG and Day, TC and Ratcliff, WC and Yunker, PJ}, title = {Geometry, packing, and evolutionary paths to increased multicellular size.}, journal = {Physical review. E}, volume = {97}, number = {5-1}, pages = {050401}, doi = {10.1103/PhysRevE.97.050401}, pmid = {29906891}, issn = {2470-0053}, abstract = {The evolutionary transition to multicellularity transformed life on earth, heralding the evolution of large, complex organisms. Recent experiments demonstrated that laboratory-evolved multicellular "snowflake yeast" readily overcome the physical barriers that limit cluster size by modifying cellular geometry [Jacobeen et al., Nat. Phys. 14, 286 (2018)10.1038/s41567-017-0002-y]. However, it is unclear why this route to large size is observed, rather than an evolved increase in intercellular bond strength. Here, we use a geometric model of the snowflake yeast growth form to examine the geometric efficiency of increasing size by modifying geometry and bond strength. We find that changing geometry is a far more efficient route to large size than evolving increased intercellular adhesion. In fact, increasing cellular aspect ratio is on average ∼13 times more effective than increasing bond strength at increasing the number of cells in a cluster. Modifying other geometric parameters, such as the geometric arrangement of mother and daughter cells, also had larger effects on cluster size than increasing bond strength. Simulations reveal that as cells reproduce, internal stress in the cluster increases rapidly; thus, increasing bond strength provides diminishing returns in cluster size. Conversely, as cells become more elongated, cellular packing density within the cluster decreases, which substantially decreases the rate of internal stress accumulation. This suggests that geometrically imposed physical constraints may have been a key early selective force guiding the emergence of multicellular complexity.}, } @article {pmid29899159, year = {2018}, author = {Zarkoob, H and Chinnathambi, S and Selby, JC and Sander, EA}, title = {Substrate deformations induce directed keratinocyte migration.}, journal = {Journal of the Royal Society, Interface}, volume = {15}, number = {143}, pages = {}, pmid = {29899159}, issn = {1742-5662}, mesh = {Amides/pharmacology ; Cell Line ; *Cell Movement ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; Humans ; Keratinocytes/*metabolism/pathology ; Pyridines/pharmacology ; *Signal Transduction ; *Wound Healing ; rho GTP-Binding Proteins/antagonists & inhibitors/metabolism ; rho-Associated Kinases/antagonists & inhibitors/metabolism ; }, abstract = {Cell migration is an essential part of many (patho)physiological processes, including keratinocyte re-epithelialization of healing wounds. Physical forces and mechanical cues from the wound bed (in addition to biochemical signals) may also play an important role in the healing process. Previously, we explored this possibility and found that polyacrylamide (PA) gel stiffness affected human keratinocyte behaviour and that mechanical deformations in soft (approx. 1.2 kPa) PA gels produced by neighbouring cells appeared to influence the process of de novo epithelial sheet formation. To clearly demonstrate that keratinocytes do respond to such deformations, we conducted a series of experiments where we observed the response of single keratinocytes to a prescribed local substrate deformation that mimicked a neighbouring cell or evolving multicellular aggregate via a servo-controlled microneedle. We also examined the effect of adding either Y27632 or blebbistatin on cell response. Our results indicate that keratinocytes do sense and respond to mechanical signals comparable to those that originate from substrate deformations imposed by neighbouring cells, a finding that could have important implications for the process of keratinocyte re-epithelialization that takes place during wound healing. Furthermore, the Rho/ROCK pathway and the engagement of NM II are both essential to substrate deformation-directed keratinocyte migration.}, } @article {pmid29892951, year = {2018}, author = {Gao, Q and Xu, S and Zhu, X and Wang, L and Yang, Z and Zhao, X}, title = {Genome-wide identification and characterization of the RIO atypical kinase family in plants.}, journal = {Genes & genomics}, volume = {40}, number = {6}, pages = {669-683}, pmid = {29892951}, issn = {2092-9293}, support = {31601385//National Natural Science Foundation of China/International ; 2016ZX08012-002//National Science and Technology Major Project/International ; 2014AA10A601-5//National High-tech R&D Program/International ; BK20160429//Natural Science Foundation of Jiangsu Province/International ; 16KJB210001//Natural Science Research Project in Universities of Jiangsu Province/International ; PPZY2015A018//Top-notch Academic Programs Project of Jiangsu Higher Education Institutions/International ; }, mesh = {Amino Acid Sequence/genetics ; Arabidopsis/genetics ; Gene Expression Regulation, Plant/genetics ; Genes, Plant/genetics ; Multigene Family ; Oryza/genetics ; Phylogeny ; Plant Proteins/genetics ; Plants/genetics ; Protein Serine-Threonine Kinases/*genetics/metabolism ; Sequence Alignment/methods ; Transcriptome/genetics ; Viridiplantae/*genetics ; Zea mays/genetics ; }, abstract = {Members of the right open reading frame (RIO) atypical kinase family are present in all three domains of life. In eukaryotes, three subfamilies have been identified: RIO1, RIO2, and RIO3. Studies have shown that the yeast and human RIO1 and RIO2 kinases are essential for the biogenesis of small ribosomal subunits. Thus far, RIO3 has been found only in multicellular eukaryotes. In this study, we systematically identified members of the RIO gene family in 37 species representing the major evolutionary lineages in Viridiplantae. A total of 84 RIO genes were identified; among them, 41 were classified as RIO1 and 43 as RIO2. However, no RIO3 gene was found in any of the species examined. Phylogenetic trees constructed for plant RIO1 and RIO2 proteins were generally congruent with the species phylogeny. Subcellular localization analyses showed that the plant RIO proteins were localized mainly in the nucleus and/or cytoplasm. Expression profile analysis of rice, maize, and Arabidopsis RIO genes in different tissues revealed similar expression patterns between RIO1 and RIO2 genes, and their expression levels were high in certain tissues. In addition, the expressions of plant RIO genes were regulated by two drugs: mycophenolic acid and actinomycin D. Function prediction using genome-wide coexpression analysis revealed that most plant RIO genes may be involved in ribosome biogenesis. Our results will be useful for the evolutionary analysis of the ancient RIO kinase family and provide a basis for further functional characterization of RIO genes in plants.}, } @article {pmid29891718, year = {2018}, author = {Smith, CCR and Tittes, S and Mendieta, JP and Collier-Zans, E and Rowe, HC and Rieseberg, LH and Kane, NC}, title = {Genetics of alternative splicing evolution during sunflower domestication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6768-6773}, pmid = {29891718}, issn = {1091-6490}, mesh = {*Alternative Splicing ; Domestication ; *Evolution, Molecular ; Helianthus/*genetics ; Plant Breeding ; Plant Proteins/genetics/metabolism ; Protein Isoforms/genetics/metabolism ; Quantitative Trait Loci ; RNA, Plant/*genetics ; Spliceosomes ; Transcriptome ; }, abstract = {Alternative splicing enables organisms to produce the diversity of proteins necessary for multicellular life by using relatively few protein-coding genes. Although differences in splicing have been identified among divergent taxa, the shorter-term evolution of splicing is understudied. The origins of novel splice forms, and the contributions of alternative splicing to major evolutionary transitions, are largely unknown. This study used transcriptomes of wild and domesticated sunflowers to examine splice differentiation and regulation during domestication. We identified substantial splicing divergence between wild and domesticated sunflowers, mainly in the form of intron retention. Transcripts with divergent splicing were enriched for seed-development functions, suggesting that artificial selection impacted splicing patterns. Mapping of quantitative trait loci (QTLs) associated with 144 differential splicing cases revealed primarily trans-acting variation affecting splicing patterns. A large proportion of identified QTLs contain known spliceosome proteins and are associated with splicing variation in multiple genes. Examining a broader set of wild and domesticated sunflower genotypes revealed that most differential splicing patterns in domesticated sunflowers likely arose from standing variation in wild Helianthus annuus and gained frequency during the domestication process. However, several domesticate-associated splicing patterns appear to be introgressed from other Helianthus species. These results suggest that sunflower domestication involved selection on pleiotropic regulatory alleles. More generally, our findings indicate that substantial differences in isoform abundances arose rapidly during a recent evolutionary transition and appear to contribute to adaptation and population divergence.}, } @article {pmid29889237, year = {2018}, author = {Leys, SP and Kahn, AS}, title = {Oxygen and the Energetic Requirements of the First Multicellular Animals.}, journal = {Integrative and comparative biology}, volume = {58}, number = {4}, pages = {666-676}, doi = {10.1093/icb/icy051}, pmid = {29889237}, issn = {1557-7023}, mesh = {Animals ; *Biological Evolution ; Ctenophora/*physiology ; *Ecosystem ; *Life History Traits ; Porifera/*physiology ; }, abstract = {The appearance of multicellular animals during the Neoproterozoic Era is thought to have coincided with oxygenation of the oceans; however, we know little about the physiological needs of early animals or about the environment they lived in. Approaches using biomarkers, fossils, and phylogenomics have provided some hints of the types of animals that may have been present during the Neoproterozoic, but extant animals are our best modern links to the theoretical ancestors of animals. Neoproterozoic oceans were low energy habitats, with low oxygen concentrations and sparse food availability for the first animals. We examined tolerance of extant ctenophores and sponges-as representatives of extant lineages of the earliest known metazoan groups-to feeding and oxygen use. A review of respiration rates in species across several phyla suggests that suspension feeders in general have a wide range of metabolic rates, but sponges have some of the highest of invertebrates and ctenophores some of the lowest. Our own studies on the metabolism of two groups of deep water sponges show that sponges have different approaches to deal with the cost of filtration and low food availability. We also confirmed that deep water sponges tolerate periods of hypoxia, but at the cost of filtration, indicating that normal feeding is energetically expensive. Predictions of oxygen levels in the Neoproterozoic suggest the last common ancestor of multicellular animals was unlikely to have filtered like modern sponges. Getting enough food at low oxygen would have been a more important driver of the evolution of early body plans.}, } @article {pmid29885639, year = {2018}, author = {Rivera-Yoshida, N and Arias Del Angel, JA and Benítez, M}, title = {Microbial multicellular development: mechanical forces in action.}, journal = {Current opinion in genetics & development}, volume = {51}, number = {}, pages = {37-45}, doi = {10.1016/j.gde.2018.05.006}, pmid = {29885639}, issn = {1879-0380}, mesh = {Bacteria/genetics/*growth & development ; *Biological Evolution ; Cell Lineage/*genetics ; *Mechanical Phenomena ; Models, Biological ; }, abstract = {Multicellular development occurs in diverse microbial lineages and involves the complex interaction among biochemical, physical and ecological factors. We focus on the mechanical forces that appear to be relevant for the scale and material qualities of individual cells and small cellular conglomerates. We review the effects of such forces on the development of some paradigmatic microorganisms, as well as their overall consequences in multicellular structures. Microbes exhibiting multicellular development have been considered models for the evolutionary transition to multicellularity. Therefore, we discuss how comparative, integrative and dynamic approaches to the mechanical effects involved in microbial development can provide valuable insights into some of the principles behind the evolutionary transition to multicellularity.}, } @article {pmid29880641, year = {2018}, author = {Miller, PW and Pokutta, S and Mitchell, JM and Chodaparambil, JV and Clarke, DN and Nelson, WJ and Weis, WI and Nichols, SA}, title = {Analysis of a vinculin homolog in a sponge (phylum Porifera) reveals that vertebrate-like cell adhesions emerged early in animal evolution.}, journal = {The Journal of biological chemistry}, volume = {293}, number = {30}, pages = {11674-11686}, pmid = {29880641}, issn = {1083-351X}, support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; R01 GM056169/GM/NIGMS NIH HHS/United States ; R01 GM114462/GM/NIGMS NIH HHS/United States ; R35 GM118064/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/analysis/metabolism ; Animals ; Cell Adhesion ; Focal Adhesions/metabolism ; Models, Molecular ; Porifera/*cytology/metabolism/ultrastructure ; Protein Binding ; Protein Conformation ; Pseudopodia/metabolism/ultrastructure ; Talin/analysis/metabolism ; Vinculin/analysis/*metabolism ; }, abstract = {The evolution of cell-adhesion mechanisms in animals facilitated the assembly of organized multicellular tissues. Studies in traditional animal models have revealed two predominant adhesion structures, the adherens junction (AJ) and focal adhesions (FAs), which are involved in the attachment of neighboring cells to each other and to the secreted extracellular matrix (ECM), respectively. The AJ (containing cadherins and catenins) and FAs (comprising integrins, talin, and paxillin) differ in protein composition, but both junctions contain the actin-binding protein vinculin. The near ubiquity of these structures in animals suggests that AJ and FAs evolved early, possibly coincident with multicellularity. However, a challenge to this perspective is that previous studies of sponges-a divergent animal lineage-indicate that their tissues are organized primarily by an alternative, sponge-specific cell-adhesion mechanism called "aggregation factor." In this study, we examined the structure, biochemical properties, and tissue localization of a vinculin ortholog in the sponge Oscarella pearsei (Op). Our results indicate that Op vinculin localizes to both cell-cell and cell-ECM contacts and has biochemical and structural properties similar to those of vertebrate vinculin. We propose that Op vinculin played a role in cell adhesion and tissue organization in the last common ancestor of sponges and other animals. These findings provide compelling evidence that sponge tissues are indeed organized like epithelia in other animals and support the notion that AJ- and FA-like structures extend to the earliest periods of animal evolution.}, } @article {pmid29875290, year = {2018}, author = {Ye, AY and Dou, Y and Yang, X and Wang, S and Huang, AY and Wei, L}, title = {A model for postzygotic mosaicisms quantifies the allele fraction drift, mutation rate, and contribution to de novo mutations.}, journal = {Genome research}, volume = {28}, number = {7}, pages = {943-951}, pmid = {29875290}, issn = {1549-5469}, mesh = {Alleles ; Child ; Female ; Genome, Human/genetics ; Humans ; Male ; Mosaicism ; Mutation/*genetics ; Mutation Rate ; Pedigree ; Polymorphism, Single Nucleotide/*genetics ; }, abstract = {The allele fraction (AF) distribution, occurrence rate, and evolutionary contribution of postzygotic single-nucleotide mosaicisms (pSNMs) remain largely unknown. In this study, we developed a mathematical model to describe the accumulation and AF drift of pSNMs during the development of multicellular organisms. By applying the model, we quantitatively analyzed two large-scale data sets of pSNMs identified from human genomes. We found that the postzygotic mutation rate per cell division during early embryogenesis, especially during the first cell division, was higher than the average mutation rate in either male or female gametes. We estimated that the stochastic cell death rate per cell cleavage during human embryogenesis was ∼5%, and parental pSNMs occurring during the first three cell divisions contributed to ∼10% of the de novo mutations observed in children. We further demonstrated that the genomic profiles of pSNMs could be used to measure the divergence distance between tissues. Our results highlight the importance of pSNMs in estimating recurrence risk and clarified the quantitative relationship between postzygotic and de novo mutations.}, } @article {pmid29866913, year = {2018}, author = {Grüter, C and Jongepier, E and Foitzik, S}, title = {Insect societies fight back: the evolution of defensive traits against social parasites.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866913}, issn = {1471-2970}, mesh = {Aggression ; Animals ; *Biological Evolution ; *Host-Parasite Interactions ; Insecta/*parasitology/*physiology ; Reproduction ; Social Behavior ; }, abstract = {Insect societies face many social parasites that exploit their altruistic behaviours or their resources. Due to the fitness costs these social parasites incur, hosts have evolved various behavioural, chemical, architectural and morphological defence traits. Similar to bacteria infecting multicellular hosts, social parasites have to successfully go through several steps to exploit their hosts. Here, we review how social insects try to interrupt this sequence of events. They can avoid parasite contact by choosing to nest in parasite-free locales or evade attacks by adapting their colony structure. Once social parasites attack, hosts attempt to detect them, which can be facilitated by adjustments in colony odour. If social parasites enter the nest, hosts can either aggressively defend their colony or take their young and flee. Nest structures are often shaped to prevent social parasite invasion or to safeguard host resources. Finally, if social parasites successfully establish themselves in host nests, hosts can rebel by killing the parasite brood or by reproducing in the parasites' presence. Hosts of social parasites can therefore develop multiple traits, leading to the evolution of complex defence portfolios of co-dependent traits. Social parasites can respond to these multi-level defences with counter-adaptations, potentially leading to geographical mosaics of coevolution.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29860723, year = {2018}, author = {Mustafin, RN and Khusnutdinova, EK}, title = {[Epigenetic hypothesis of the role of peptides in aging.].}, journal = {Advances in gerontology = Uspekhi gerontologii}, volume = {31}, number = {1}, pages = {10-20}, pmid = {29860723}, issn = {1561-9125}, mesh = {Aging/*genetics ; *Epigenesis, Genetic ; Humans ; Peptides/*genetics ; RNA, Long Noncoding ; }, abstract = {In regulation of gene expression in the ontogenesis of multicellular eukaryotes, in addition to transcription factors, an important role is played by epigenetic factors that control the release of genetic information in each cell division. Many binding sites for the transcription factors were derived from transposons sequences. Mobile elements are also important sources of non-coding RNA. Due to this, transposons have an indirect effect on gene expression and genome methylation. In evolution, transposons serve as important sources for the origin of new protein and proteins domains. A number of studies have identified that long non-coding RNAs and microRNAs can be translated into functional peptides. At the same time, transposons remain active in the hypothalamus of adult humans, which is consistent with the transcription of non-coding RNAs in these structures, which may be key in aging.}, } @article {pmid29856957, year = {2018}, author = {Sebé-Pedrós, A and Saudemont, B and Chomsky, E and Plessier, F and Mailhé, MP and Renno, J and Loe-Mie, Y and Lifshitz, A and Mukamel, Z and Schmutz, S and Novault, S and Steinmetz, PRH and Spitz, F and Tanay, A and Marlow, H}, title = {Cnidarian Cell Type Diversity and Regulation Revealed by Whole-Organism Single-Cell RNA-Seq.}, journal = {Cell}, volume = {173}, number = {6}, pages = {1520-1534.e20}, doi = {10.1016/j.cell.2018.05.019}, pmid = {29856957}, issn = {1097-4172}, support = {724824/ERC_/European Research Council/International ; }, mesh = {Actins/chemistry ; Amino Acid Motifs ; Animals ; Chromatin/metabolism ; Cluster Analysis ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Genome ; Genomics ; Neurons/*physiology ; Phylogeny ; *RNA ; Sea Anemones/genetics/*physiology ; Sequence Analysis, RNA ; Transcriptome ; Tubulin/chemistry ; }, abstract = {The emergence and diversification of cell types is a leading factor in animal evolution. So far, systematic characterization of the gene regulatory programs associated with cell type specificity was limited to few cell types and few species. Here, we perform whole-organism single-cell transcriptomics to map adult and larval cell types in the cnidarian Nematostella vectensis, a non-bilaterian animal with complex tissue-level body-plan organization. We uncover eight broad cell classes in Nematostella, including neurons, cnidocytes, and digestive cells. Each class comprises different subtypes defined by the expression of multiple specific markers. In particular, we characterize a surprisingly diverse repertoire of neurons, which comparative analysis suggests are the result of lineage-specific diversification. By integrating transcription factor expression, chromatin profiling, and sequence motif analysis, we identify the regulatory codes that underlie Nematostella cell-specific expression. Our study reveals cnidarian cell type complexity and provides insights into the evolution of animal cell-specific genomic regulation.}, } @article {pmid29853554, year = {2018}, author = {Toda, S and Blauch, LR and Tang, SKY and Morsut, L and Lim, WA}, title = {Programming self-organizing multicellular structures with synthetic cell-cell signaling.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {156-162}, pmid = {29853554}, issn = {1095-9203}, support = {K99 EB021030/EB/NIBIB NIH HHS/United States ; P50 GM081879/GM/NIGMS NIH HHS/United States ; R00 EB021030/EB/NIBIB NIH HHS/United States ; T32 GM008412/GM/NIGMS NIH HHS/United States ; /HHMI_/Howard Hughes Medical Institute/United States ; }, mesh = {*Artificial Cells ; Cell Adhesion ; *Cell Communication ; Cell Engineering/*methods ; *Cells ; *Morphogenesis ; Signal Transduction ; Spheroids, Cellular/cytology/physiology ; }, abstract = {A common theme in the self-organization of multicellular tissues is the use of cell-cell signaling networks to induce morphological changes. We used the modular synNotch juxtacrine signaling platform to engineer artificial genetic programs in which specific cell-cell contacts induced changes in cadherin cell adhesion. Despite their simplicity, these minimal intercellular programs were sufficient to yield assemblies with hallmarks of natural developmental systems: robust self-organization into multidomain structures, well-choreographed sequential assembly, cell type divergence, symmetry breaking, and the capacity for regeneration upon injury. The ability of these networks to drive complex structure formation illustrates the power of interlinking cell signaling with cell sorting: Signal-induced spatial reorganization alters the local signals received by each cell, resulting in iterative cycles of cell fate branching. These results provide insights into the evolution of multicellularity and demonstrate the potential to engineer customized self-organizing tissues or materials.}, } @article {pmid29851258, year = {2018}, author = {Schaefke, B and Sun, W and Li, YS and Fang, L and Chen, W}, title = {The evolution of posttranscriptional regulation.}, journal = {Wiley interdisciplinary reviews. RNA}, volume = {9}, number = {5}, pages = {e1485}, doi = {10.1002/wrna.1485}, pmid = {29851258}, issn = {1757-7012}, abstract = {"DNA makes RNA makes protein." After transcription, mRNAs undergo a series of intertwining processes to be finally translated into functional proteins. The "posttranscriptional" regulation (PTR) provides cells an extended option to fine-tune their proteomes. To meet the demands of complex organism development and the appropriate response to environmental stimuli, every step in these processes needs to be finely regulated. Moreover, changes in these regulatory processes are important driving forces underlying the evolution of phenotypic differences across different species. The major PTR mechanisms discussed in this review include the regulation of splicing, polyadenylation, decay, and translation. For alternative splicing and polyadenylation, we mainly discuss their evolutionary dynamics and the genetic changes underlying the regulatory differences in cis-elements versus trans-factors. For mRNA decay and translation, which, together with transcription, determine the cellular RNA or protein abundance, we focus our discussion on how their divergence coordinates with transcriptional changes to shape the evolution of gene expression. Then to highlight the importance of PTR in the evolution of higher complexity, we focus on their roles in two major phenomena during eukaryotic evolution: the evolution of multicellularity and the division of labor between different cell types and tissues; and the emergence of diverse, often highly specialized individual phenotypes, especially those concerning behavior in eusocial insects. This article is categorized under: RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution Translation > Translation Regulation RNA Processing > Splicing Regulation/Alternative Splicing.}, } @article {pmid29850801, year = {2018}, author = {Nishiyama, E and Ohshima, K}, title = {Cross-Kingdom Commonality of a Novel Insertion Signature of RTE-Related Short Retroposons.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1471-1483}, pmid = {29850801}, issn = {1759-6653}, mesh = {Animals ; DNA Transposable Elements/*genetics ; Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Genome, Plant/genetics ; Lizards/genetics ; Long Interspersed Nucleotide Elements/genetics ; Magnoliopsida/genetics ; Mammals/genetics ; Microsatellite Repeats/genetics ; Mutagenesis, Insertional/methods ; Phylogeny ; Retroelements/*genetics ; Reverse Transcription/genetics ; Short Interspersed Nucleotide Elements/genetics ; }, abstract = {In multicellular organisms, such as vertebrates and flowering plants, horizontal transfer (HT) of genetic information is thought to be a rare event. However, recent findings unveiled unexpectedly frequent HT of RTE-clade LINEs. To elucidate the molecular footprints of the genomic integration machinery of RTE-related retroposons, the sequence patterns surrounding the insertion sites of plant Au-like SINE families were analyzed in the genomes of a wide variety of flowering plants. A novel and remarkable finding regarding target site duplications (TSDs) for SINEs was they start with thymine approximately one helical pitch (ten nucleotides) downstream of a thymine stretch. This TSD pattern was found in RTE-clade LINEs, which share the 3'-end sequence of these SINEs, in the genome of leguminous plants. These results demonstrably show that Au-like SINEs were mobilized by the enzymatic machinery of RTE-clade LINEs. Further, we discovered the same TSD pattern in animal SINEs from lizard and mammals, in which the RTE-clade LINEs sharing the 3'-end sequence with these animal SINEs showed a distinct TSD pattern. Moreover, a significant correlation was observed between the first nucleotide of TSDs and microsatellite-like sequences found at the 3'-ends of SINEs and LINEs. We propose that RTE-encoded protein could preferentially bind to a DNA region that contains a thymine stretch to cleave a phosphodiester bond downstream of the stretch. Further, determination of cleavage sites and/or efficiency of primer sites for reverse transcription may depend on microsatellite-like repeats in the RNA template. Such a unique mechanism may have enabled retroposons to successfully expand in frontier genomes after HT.}, } @article {pmid29849168, year = {2018}, author = {Woo, C and An, C and Xu, S and Yi, SM and Yamamoto, N}, title = {Taxonomic diversity of fungi deposited from the atmosphere.}, journal = {The ISME journal}, volume = {12}, number = {8}, pages = {2051-2060}, pmid = {29849168}, issn = {1751-7370}, mesh = {*Air Microbiology ; Atmosphere ; Environmental Monitoring ; Fungi/*classification/genetics/*isolation & purification ; Phylogeny ; Spores, Fungal/classification/genetics/isolation & purification ; }, abstract = {Fungi release spores into the global atmosphere. The emitted spores are deposited to the surface of the Earth by sedimentation (dry deposition) and precipitation (wet deposition), and therefore contribute to the global cycling of substances. However, knowledge is scarce regarding the diversities of fungi deposited from the atmosphere. Here, an automatic dry and wet deposition sampler and high-throughput sequencing plus quantitative PCR were used to observe taxonomic diversities and flux densities of atmospheric fungal deposition. Taxon-specific fungal deposition velocities and aerodynamic diameters (da) were determined using a collocated cascade impactor for volumetric, particle-size-resolved air sampling. Large multicellular spore-producing dothideomycetes (da ≥ 10.0 μm) were predominant in dry deposition, with a mean velocity of 0.80 cm s[-1] for all fungal taxa combined. Higher taxonomic richness was observed in fungal assemblages in wet deposition than in dry deposition, suggesting the presence of fungal taxa that are deposited only in wet form. In wet deposition, agaricomycetes, including mushroom-forming fungi, and sordariomycetes, including plant pathogenic species, were enriched, indicating that such fungal spores serve as nuclei in clouds, and/or are discharged preferentially during precipitation. Moreover, this study confirmed that fungal assemblage memberships and structures were significantly different between dry and wet deposition (P-test, p < 0.001). Overall, these findings suggest taxon-specific involvement of fungi in precipitation, and provide important insights into potential links between environmental changes that can disturb regional microbial communities (e.g., deforestation) and changes in precipitation patterns that might be mediated by changes in microbial communities in the atmosphere.}, } @article {pmid29848439, year = {2018}, author = {Hamada, M and Schröder, K and Bathia, J and Kürn, U and Fraune, S and Khalturina, M and Khalturin, K and Shinzato, C and Satoh, N and Bosch, TC}, title = {Metabolic co-dependence drives the evolutionarily ancient Hydra-Chlorella symbiosis.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {29848439}, issn = {2050-084X}, mesh = {Animals ; *Biological Evolution ; Chlorella/drug effects/genetics/*metabolism ; Conserved Sequence ; Darkness ; Epithelial Cells/drug effects/metabolism ; Gene Expression Regulation ; Genome ; Hydra/drug effects/genetics/growth & development/*metabolism ; Molecular Sequence Annotation ; Nitrates/metabolism ; Nitrogen/metabolism ; Photosynthesis/genetics ; RNA, Ribosomal, 18S/genetics/metabolism ; Species Specificity ; Sugars/pharmacology ; *Symbiosis/drug effects/genetics ; }, abstract = {Many multicellular organisms rely on symbiotic associations for support of metabolic activity, protection, or energy. Understanding the mechanisms involved in controlling such interactions remains a major challenge. In an unbiased approach we identified key players that control the symbiosis between Hydra viridissima and its photosynthetic symbiont Chlorella sp. A99. We discovered significant up-regulation of Hydra genes encoding a phosphate transporter and glutamine synthetase suggesting regulated nutrition supply between host and symbionts. Interestingly, supplementing the medium with glutamine temporarily supports in vitro growth of the otherwise obligate symbiotic Chlorella, indicating loss of autonomy and dependence on the host. Genome sequencing of Chlorella sp. A99 revealed a large number of amino acid transporters and a degenerated nitrate assimilation pathway, presumably as consequence of the adaptation to the host environment. Our observations portray ancient symbiotic interactions as a codependent partnership in which exchange of nutrients appears to be the primary driving force.}, } @article {pmid29846592, year = {2018}, author = {Paps, J}, title = {What Makes an Animal? The Molecular Quest for the Origin of the Animal Kingdom.}, journal = {Integrative and comparative biology}, volume = {58}, number = {4}, pages = {654-665}, doi = {10.1093/icb/icy036}, pmid = {29846592}, issn = {1557-7023}, mesh = {Animals ; *Biological Evolution ; Evolution, Molecular ; Genome ; Genomics/*methods ; Invertebrates/classification/*genetics ; Molecular Biology/*methods ; *Phylogeny ; Vertebrates/classification/genetics ; }, abstract = {What makes an animal? To find the answer we need to integrate data from disciplines such as phylogenetics, paleontology, ecology, development, anatomy, and physiology, as well as molecular biology and genomics. Knowledge of which groups branched before and after the origin of animals is essential. Recent advances in molecular phylogenetics, together with the discovery of new eukaryotic lineages, have drawn a new picture of the ancestry of animals. The nature of the early diverging animal lineages and the timing of the transition are in a state of flux. Various factors have been linked to this striking transition to multicellularity, including changes in environmental conditions and the ecological interactions between unicellular eukaryotes. The current wealth of genomic data has also shed new light on this question. The analysis of the genome of various close relatives of animals has revealed the importance that recycling of ancient genes into metazoan biological functions played into animal origins. A recent study reconstructing the genome of the last common ancestor of extant animals has unveiled an unprecedented emergence of new genes, highlighting the role of genomic novelty in the origin of metazoans.}, } @article {pmid29844338, year = {2018}, author = {Pinhal, D and Bovolenta, LA and Moxon, S and Oliveira, AC and Nachtigall, PG and Acencio, ML and Patton, JG and Hilsdorf, AWS and Lemke, N and Martins, C}, title = {Genome-wide microRNA screening in Nile tilapia reveals pervasive isomiRs' transcription, sex-biased arm switching and increasing complexity of expression throughout development.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {8248}, pmid = {29844338}, issn = {2045-2322}, mesh = {Animals ; Cichlids/*genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genetic Testing ; Genome-Wide Association Study ; Genomics/*methods ; Life Cycle Stages ; Male ; MicroRNAs/*genetics ; Protein Isoforms/*genetics ; Sequence Analysis, RNA ; Sex Characteristics ; Transcription, Genetic ; }, abstract = {MicroRNAs (miRNAs) are key regulators of gene expression in multicellular organisms. The elucidation of miRNA function and evolution depends on the identification and characterization of miRNA repertoire of strategic organisms, as the fast-evolving cichlid fishes. Using RNA-seq and comparative genomics we carried out an in-depth report of miRNAs in Nile tilapia (Oreochromis niloticus), an emergent model organism to investigate evo-devo mechanisms. Five hundred known miRNAs and almost one hundred putative novel vertebrate miRNAs have been identified, many of which seem to be teleost-specific, cichlid-specific or tilapia-specific. Abundant miRNA isoforms (isomiRs) were identified with modifications in both 5p and 3p miRNA transcripts. Changes in arm usage (arm switching) of nine miRNAs were detected in early development, adult stage and even between male and female samples. We found an increasing complexity of miRNA expression during ontogenetic development, revealing a remarkable synchronism between the rate of new miRNAs recruitment and morphological changes. Overall, our results enlarge vertebrate miRNA collection and reveal a notable differential ratio of miRNA arms and isoforms influenced by sex and developmental life stage, providing a better picture of the evolutionary and spatiotemporal dynamics of miRNAs.}, } @article {pmid29807994, year = {2018}, author = {Cooper, GA and West, SA}, title = {Division of labour and the evolution of extreme specialization.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1161-1167}, doi = {10.1038/s41559-018-0564-9}, pmid = {29807994}, issn = {2397-334X}, mesh = {Animals ; *Biological Evolution ; *Cooperative Behavior ; Models, Biological ; *Selection, Genetic ; Social Behavior ; }, abstract = {Division of labour is a common feature of social groups, from biofilms to complex animal societies. However, we lack a theoretical framework that can explain why division of labour has evolved on certain branches of the tree of life but not others. Here, we model the division of labour over a cooperative behaviour, considering both when it should evolve and the extent to which the different types should become specialized. We found that: (1) division of labour is usually-but not always-favoured by high efficiency benefits to specialization and low within-group conflict; and (2) natural selection favours extreme specialization, where some individuals are completely dependent on the helping behaviour of others. We make a number of predictions, several of which are supported by the existing empirical data, from microbes and animals, while others suggest novel directions for empirical work. More generally, we show how division of labour can lead to mutual dependence between different individuals and hence drive major evolutionary transitions, such as those to multicellularity and eusociality.}, } @article {pmid29802408, year = {2018}, author = {Reeves, MQ and Kandyba, E and Harris, S and Del Rosario, R and Balmain, A}, title = {Multicolour lineage tracing reveals clonal dynamics of squamous carcinoma evolution from initiation to metastasis.}, journal = {Nature cell biology}, volume = {20}, number = {6}, pages = {699-709}, pmid = {29802408}, issn = {1476-4679}, support = {U01 CA176287/CA/NCI NIH HHS/United States ; U01 CA217864/CA/NCI NIH HHS/United States ; R35 CA210018/CA/NCI NIH HHS/United States ; F31 CA206459/CA/NCI NIH HHS/United States ; T32 GM008568/GM/NIGMS NIH HHS/United States ; R01 CA184510/CA/NCI NIH HHS/United States ; }, mesh = {9,10-Dimethyl-1,2-benzanthracene ; Animals ; Carcinoma, Squamous Cell/chemically induced/*genetics/metabolism/secondary ; *Cell Lineage ; Cell Movement/*genetics ; Cell Proliferation/genetics ; Cell Transformation, Neoplastic/chemically induced/*genetics/metabolism/pathology ; *Clonal Evolution ; Epithelial Cells/metabolism/*pathology ; Female ; Gene Expression Regulation, Neoplastic ; Genes, ras ; Genetic Predisposition to Disease ; Male ; Mice, Transgenic ; Mutation ; Neoplasms, Experimental/chemically induced/*genetics/metabolism/pathology ; Phenotype ; Skin Neoplasms/chemically induced/*genetics/metabolism/pathology ; Tetradecanoylphorbol Acetate ; Time Factors ; Tumor Burden/genetics ; }, abstract = {Tumour cells are subjected to evolutionary selection pressures during progression from initiation to metastasis. We analysed the clonal evolution of squamous skin carcinomas induced by DMBA/TPA treatment using the K5CreER-Confetti mouse and stage-specific lineage tracing. We show that benign tumours are polyclonal, but only one population contains the Hras driver mutation. Thus, benign papillomas are monoclonal in origin but recruit neighbouring epithelial cells during growth. Papillomas that never progress to malignancy retain several distinct clones, whereas progression to carcinoma is associated with a clonal sweep. Newly generated clones within carcinomas demonstrate intratumoural invasion and clonal intermixing, often giving rise to metastases containing two or more distinct clones derived from the matched primary tumour. These data demonstrate that late-stage tumour progression and dissemination are governed by evolutionary selection pressures that operate at a multicellular level and, therefore, differ from the clonal events that drive initiation and the benign-malignant transition.}, } @article {pmid29797026, year = {2018}, author = {Hauser, CJ and Otterbein, LE}, title = {Danger signals from mitochondrial DAMPS in trauma and post-injury sepsis.}, journal = {European journal of trauma and emergency surgery : official publication of the European Trauma Society}, volume = {44}, number = {3}, pages = {317-324}, pmid = {29797026}, issn = {1863-9941}, support = {W81XWH-16-1-0464//U.S. Department of Defense/ ; }, mesh = {Alarmins/*immunology ; Animals ; Humans ; Immunity, Innate ; Inflammation/*immunology ; Mitochondria/*immunology ; Signal Transduction/immunology ; Wounds and Injuries/*immunology ; }, abstract = {In all multicellular organisms, immediate host responses to both sterile and infective threat are initiated by very primitive systems now grouped together under the general term 'danger responses'. Danger signals are generated when primitive 'pattern recognition receptors' (PRR) encounter activating 'alarmins'. These molecular species may be of pathogenic infective origin (pathogen-associated molecular patterns) or of sterile endogenous origin (danger-associated molecular patterns). There are many sterile and infective alarmins and there is considerable overlap in their ability to activate PRR, but in all cases the end result is inflammation. It is the overlap between sterile and infective signals acting via a relatively limited number of PRR that generally underlies the great clinical similarity we see between sterile and infective systemic inflammatory responses. Mitochondria (MT) are evolutionarily derived from bacteria, and thus they sit at the crossroads between sterile and infective danger signal pathways. Many of the molecular species in mitochondria are alarmins, and so the release of MT from injured cells results in a wide variety of inflammatory events. This paper discusses the known participation of MT in inflammation and reviews what is known about how the major.}, } @article {pmid29789717, year = {2018}, author = {Al Habyan, S and Kalos, C and Szymborski, J and McCaffrey, L}, title = {Multicellular detachment generates metastatic spheroids during intra-abdominal dissemination in epithelial ovarian cancer.}, journal = {Oncogene}, volume = {37}, number = {37}, pages = {5127-5135}, pmid = {29789717}, issn = {1476-5594}, mesh = {Abdomen/*pathology ; Anoikis/physiology ; Ascites/pathology ; Carcinoma, Ovarian Epithelial/*pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm/physiology ; Female ; Humans ; Neoplasm Recurrence, Local/pathology ; Ovarian Neoplasms/*pathology ; Spheroids, Cellular/*pathology ; }, abstract = {Ovarian cancer is the most lethal gynecological cancer, where survival rates have had modest improvement over the last 30 years. Metastasis of cancer cells is a major clinical problem, and patient mortality occurs when ovarian cancer cells spread beyond the confinement of ovaries. Disseminated ovarian cancer cells typically spread within the abdomen, where ascites accumulation aids in their transit. Metastatic ascites contain multicellular spheroids, which promote chemo-resistance and recurrence. However, little is known about the origin and mechanisms through which spheroids arise. Using live-imaging of 3D culture models and animal models, we report that epithelial ovarian cancer (EOC) cells, the most common type of ovarian cancer, can spontaneously detach as either single cells or clusters. We report that clusters are more resistant to anoikis and have a potent survival advantage over single cells. Using in vivo lineage tracing, we found that multicellular spheroids arise preferentially from collective detachment, rather than aggregation in the abdomen. Finally, we report that multicellular spheroids from collective detachment are capable of seeding intra-abdominal metastases that retain intra-tumoral heterogeneity from the primary tumor.}, } @article {pmid29788279, year = {2018}, author = {Tarver, JE and Taylor, RS and Puttick, MN and Lloyd, GT and Pett, W and Fromm, B and Schirrmeister, BE and Pisani, D and Peterson, KJ and Donoghue, PCJ}, title = {Well-Annotated microRNAomes Do Not Evidence Pervasive miRNA Loss.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1457-1470}, pmid = {29788279}, issn = {1759-6653}, mesh = {Animals ; Conserved Sequence/genetics ; Evolution, Molecular ; MicroRNAs/*genetics ; Molecular Sequence Annotation/methods ; Phenotype ; Phylogeny ; }, abstract = {microRNAs are conserved noncoding regulatory factors implicated in diverse physiological and developmental processes in multicellular organisms, as causal macroevolutionary agents and for phylogeny inference. However, the conservation and phylogenetic utility of microRNAs has been questioned on evidence of pervasive loss. Here, we show that apparent widespread losses are, largely, an artefact of poorly sampled and annotated microRNAomes. Using a curated data set of animal microRNAomes, we reject the view that miRNA families are never lost, but they are rarely lost (92% are never lost). A small number of families account for a majority of losses (1.7% of families account for >45% losses), and losses are associated with lineages exhibiting phenotypic simplification. Phylogenetic analyses based on the presence/absence of microRNA families among animal lineages, and based on microRNA sequences among Osteichthyes, demonstrate the power of these small data sets in phylogenetic inference. Perceptions of widespread evolutionary loss of microRNA families are due to the uncritical use of public archives corrupted by spurious microRNA annotations, and failure to discriminate false absences that occur because of incomplete microRNAome annotation.}, } @article {pmid29775683, year = {2018}, author = {Dechristé, G and Fehrenbach, J and Griseti, E and Lobjois, V and Poignard, C}, title = {Viscoelastic modeling of the fusion of multicellular tumor spheroids in growth phase.}, journal = {Journal of theoretical biology}, volume = {454}, number = {}, pages = {102-109}, doi = {10.1016/j.jtbi.2018.05.005}, pmid = {29775683}, issn = {1095-8541}, mesh = {Cell Fusion ; *Cell Proliferation ; HCT116 Cells ; Humans ; Kinetics ; *Models, Theoretical ; Neoplasms/*pathology/physiopathology ; Rheology ; Spheroids, Cellular/*pathology/*physiology ; Surface Tension ; Viscoelastic Substances/metabolism ; }, abstract = {BACKGROUND: Since several decades, the experiments have highlighted the analogy of fusing cell aggregates with liquid droplets. The physical macroscopic models have been derived under incompressible assumptions. The aim of this paper is to provide a 3D model of growing spheroids, which is more relevant regarding embryo cell aggregates or tumor cell spheroids.

METHODS: We extend the past approach to a compressible 3D framework in order to account for the tumor spheroid growth. We exhibit the crucial importance of the effective surface tension, and of the inner pressure of the spheroid to describe precisely the fusion. The experimental data were obtained on spheroids of colon carcinoma human cells (HCT116 cell line). After 3 or 6 days of culture, two identical spheroids were transferred in one well and their fusion was monitored by live videomicroscopy acquisition each 2 h during 72 h. From these images the neck radius and the diameter of the assembly of the fusing spheroids are extracted.

RESULTS: The numerical model is fitted with the experiments. It is worth noting that the time evolution of both neck radius and spheroid diameter are quantitatively obtained. The interesting feature lies in the fact that such measurements characterise the macroscopic rheological properties of the tumor spheroids.

CONCLUSIONS: The experimental determination of the kinetics of neck radius and overall diameter during spheroids fusion characterises the rheological properties of the spheroids. The consistency of the model is shown by fitting the model with two different experiments, enhancing the importance of both surface tension and cell proliferation.

GENERAL SIGNIFICANCE: The paper sheds new light on the macroscopic rheological properties of tumor spheroids. It emphasizes the role of the surface tension and the inner pressure in the fusion of growing spheroid. Under geometrical assumptions, the model reduces to a 2-parameter differential equation fit with experimental measurements. The 3-D partial differential system makes it possible to study the fusion of spheroids in non-symmetrical or more general frameworks.}, } @article {pmid29760902, year = {2018}, author = {Quintero-Galvis, JF and Paleo-López, R and Solano-Iguaran, JJ and Poupin, MJ and Ledger, T and Gaitan-Espitia, JD and Antoł, A and Travisano, M and Nespolo, RF}, title = {Exploring the evolution of multicellularity in Saccharomyces cerevisiae under bacteria environment: An experimental phylogenetics approach.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4619-4630}, pmid = {29760902}, issn = {2045-7758}, abstract = {There have been over 25 independent unicellular to multicellular evolutionary transitions, which have been transformational in the complexity of life. All of these transitions likely occurred in communities numerically dominated by unicellular organisms, mostly bacteria. Hence, it is reasonable to expect that bacteria were involved in generating the ecological conditions that promoted the stability and proliferation of the first multicellular forms as protective units. In this study, we addressed this problem by analyzing the occurrence of multicellularity in an experimental phylogeny of yeasts (Sacharomyces cerevisiae) a model organism that is unicellular but can generate multicellular clusters under some conditions. We exposed a single ancestral population to periodic divergences, coevolving with a cocktail of environmental bacteria that were inoculated to the environment of the ancestor, and compared to a control (no bacteria). We quantified culturable microorganisms to the level of genera, finding up to 20 taxa (all bacteria) that competed with the yeasts during diversification. After 600 generations of coevolution, the yeasts produced two types of multicellular clusters: clonal and aggregative. Whereas clonal clusters were present in both treatments, aggregative clusters were only present under the bacteria treatment and showed significant phylogenetic signal. However, clonal clusters showed different properties if bacteria were present as follows: They were more abundant and significantly smaller than in the control. These results indicate that bacteria are important modulators of the occurrence of multicellularity, providing support to the idea that they generated the ecological conditions-promoting multicellularity.}, } @article {pmid29755113, year = {2018}, author = {Jézéquel, P and Campone, M}, title = {Comment on "How the evolution of multicellularity set the stage for cancer".}, journal = {British journal of cancer}, volume = {119}, number = {1}, pages = {133-134}, pmid = {29755113}, issn = {1532-1827}, mesh = {Humans ; *Neoplasms ; }, } @article {pmid29752387, year = {2018}, author = {Parra-Acero, H and Ros-Rocher, N and Perez-Posada, A and Kożyczkowska, A and Sánchez-Pons, N and Nakata, A and Suga, H and Najle, SR and Ruiz-Trillo, I}, title = {Transfection of Capsaspora owczarzaki, a close unicellular relative of animals.}, journal = {Development (Cambridge, England)}, volume = {145}, number = {10}, pages = {}, pmid = {29752387}, issn = {1477-9129}, mesh = {Animals ; Biological Evolution ; DNA/*genetics ; Evolution, Molecular ; Gene Expression Regulation/genetics ; Genome, Protozoan/*genetics ; Mesomycetozoea/*genetics ; Plasmids/*genetics ; Transfection/*methods ; }, abstract = {How animals emerged from their unicellular ancestor remains a major evolutionary question. New genome data from the closest unicellular relatives of animals have provided important insights into the evolution of animal multicellularity. We know that the unicellular ancestor of animals had an unexpectedly complex genetic repertoire, including many genes that are key to animal development and multicellularity. Thus, assessing the function of these genes among unicellular relatives of animals is key to understanding how they were co-opted at the onset of the Metazoa. However, such analyses have been hampered by the lack of genetic tools. Progress has been made in choanoflagellates and teretosporeans, two of the three lineages closely related to animals, whereas no tools are yet available for functional analysis in the third lineage: the filastereans. Importantly, filastereans have a striking repertoire of genes involved in transcriptional regulation and other developmental processes. Here, we describe a reliable transfection method for the filasterean Capsaspora owczarzaki We also provide a set of constructs for visualising subcellular structures in live cells. These tools convert Capsaspora into a unique experimentally tractable organism to use to investigate the origin and evolution of animal multicellularity.}, } @article {pmid29738987, year = {2018}, author = {Tasic, B}, title = {Single cell transcriptomics in neuroscience: cell classification and beyond.}, journal = {Current opinion in neurobiology}, volume = {50}, number = {}, pages = {242-249}, doi = {10.1016/j.conb.2018.04.021}, pmid = {29738987}, issn = {1873-6882}, mesh = {Animals ; Biological Evolution ; Humans ; Neurons/classification/*metabolism ; *Neurosciences ; Single-Cell Analysis/methods ; Transcriptome/*physiology ; }, abstract = {Biology has been facing a daunting problem since the cell was understood to be the building block of metazoans: how do we study multicellular systems, when a universal approach to characterize their building blocks and classify them does not exist? Metazoan diversity has not helped: there are many model and non-model organisms, developmental and adult stages, healthy and diseased states. Here, I review the application of single cell transcriptomics to cell classification in neuroscience and its corollaries: the differentially expressed genes discovered in this process are a treasure trove for understanding cell type function and enabling specific access to those types. The advancements and widespread adoption of single-cell transcriptomics are bound to transform our understanding of neural system development, function, pathology and evolution.}, } @article {pmid29735660, year = {2018}, author = {Elsner, D and Meusemann, K and Korb, J}, title = {Longevity and transposon defense, the case of termite reproductives.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5504-5509}, pmid = {29735660}, issn = {1091-6490}, mesh = {Animals ; *DNA Transposable Elements ; *Gene Expression Regulation ; High-Throughput Nucleotide Sequencing ; Isoptera/*genetics ; *Longevity ; RNA, Small Interfering/*genetics ; *Reproduction ; }, abstract = {Social insects are promising new models in aging research. Within single colonies, longevity differences of several magnitudes exist that can be found elsewhere only between different species. Reproducing queens (and, in termites, also kings) can live for several decades, whereas sterile workers often have a lifespan of a few weeks only. We studied aging in the wild in a highly social insect, the termite Macrotermes bellicosus, which has one of the most pronounced longevity differences between reproductives and workers. We show that gene-expression patterns differed little between young and old reproductives, implying negligible aging. By contrast, old major workers had many genes up-regulated that are related to transposable elements (TEs), which can cause aging. Strikingly, genes from the PIWI-interacting RNA (piRNA) pathway, which are generally known to silence TEs in the germline of multicellular animals, were down-regulated only in old major workers but not in reproductives. Continued up-regulation of the piRNA defense commonly found in the germline of animals can explain the long life of termite reproductives, implying somatic cooption of germline defense during social evolution. This presents a striking germline/soma analogy as envisioned by the superorganism concept: the reproductives and workers of a colony reflect the germline and soma of multicellular animals, respectively. Our results provide support for the disposable soma theory of aging.}, } @article {pmid29731304, year = {2018}, author = {Maclean, AE and Hertle, AP and Ligas, J and Bock, R and Balk, J and Meyer, EH}, title = {Absence of Complex I Is Associated with Diminished Respiratory Chain Function in European Mistletoe.}, journal = {Current biology : CB}, volume = {28}, number = {10}, pages = {1614-1619.e3}, doi = {10.1016/j.cub.2018.03.036}, pmid = {29731304}, issn = {1879-0445}, mesh = {Electron Transport/*physiology ; Electron Transport Complex I/*genetics/metabolism ; Mitochondria/*metabolism ; Oxidative Phosphorylation ; Viscum album/*genetics/metabolism ; }, abstract = {Parasitism is a life history strategy found across all domains of life whereby nutrition is obtained from a host. It is often associated with reductive evolution of the genome, including loss of genes from the organellar genomes [1, 2]. In some unicellular parasites, the mitochondrial genome (mitogenome) has been lost entirely, with far-reaching consequences for the physiology of the organism [3, 4]. Recently, mitogenome sequences of several species of the hemiparasitic plant mistletoe (Viscum sp.) have been reported [5, 6], revealing a striking loss of genes not seen in any other multicellular eukaryotes. In particular, the nad genes encoding subunits of respiratory complex I are all absent and other protein-coding genes are also lost or highly diverged in sequence, raising the question what remains of the respiratory complexes and mitochondrial functions. Here we show that oxidative phosphorylation (OXPHOS) in European mistletoe, Viscum album, is highly diminished. Complex I activity and protein subunits of complex I could not be detected. The levels of complex IV and ATP synthase were at least 5-fold lower than in the non-parasitic model plant Arabidopsis thaliana, whereas alternative dehydrogenases and oxidases were higher in abundance. Carbon flux analysis indicates that cytosolic reactions including glycolysis are greater contributors to ATP synthesis than the mitochondrial tricarboxylic acid (TCA) cycle. Our results describe the extreme adjustments in mitochondrial functions of the first reported multicellular eukaryote without complex I.}, } @article {pmid29730580, year = {2018}, author = {Vijay, K}, title = {Toll-like receptors in immunity and inflammatory diseases: Past, present, and future.}, journal = {International immunopharmacology}, volume = {59}, number = {}, pages = {391-412}, pmid = {29730580}, issn = {1878-1705}, mesh = {Animals ; Genetic Predisposition to Disease ; Humans ; *Immunity, Innate ; Infections/genetics/immunology ; Inflammation/genetics/*immunology ; Polymorphism, Genetic ; Toll-Like Receptors/genetics/*immunology ; }, abstract = {The immune system is a very diverse system of the host that evolved during evolution to cope with various pathogens present in the vicinity of environmental surroundings inhabited by multicellular organisms ranging from achordates to chordates (including humans). For example, cells of immune system express various pattern recognition receptors (PRRs) that detect danger via recognizing specific pathogen-associated molecular patterns (PAMPs) and mount a specific immune response. Toll-like receptors (TLRs) are one of these PRRs expressed by various immune cells. However, they were first discovered in the Drosophila melanogaster (common fruit fly) as genes/proteins important in embryonic development and dorso-ventral body patterning/polarity. Till date, 13 different types of TLRs (TLR1-TLR13) have been discovered and described in mammals since the first discovery of TLR4 in humans in late 1997. This discovery of TLR4 in humans revolutionized the field of innate immunity and thus the immunology and host-pathogen interaction. Since then TLRs are found to be expressed on various immune cells and have been targeted for therapeutic drug development for various infectious and inflammatory diseases including cancer. Even, Single nucleotide polymorphisms (SNPs) among various TLR genes have been identified among the different human population and their association with susceptibility/resistance to certain infections and other inflammatory diseases. Thus, in the present review the current and future importance of TLRs in immunity, their pattern of expression among various immune cells along with TLR based therapeutic approach is reviewed.}, } @article {pmid29728614, year = {2018}, author = {Pehr, K and Love, GD and Kuznetsov, A and Podkovyrov, V and Junium, CK and Shumlyanskyy, L and Sokur, T and Bekker, A}, title = {Ediacara biota flourished in oligotrophic and bacterially dominated marine environments across Baltica.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {1807}, pmid = {29728614}, issn = {2041-1723}, mesh = {Asia ; Bacteria/growth & development ; Biological Evolution ; Biomarkers/analysis ; *Biota ; Ecosystem ; Europe ; *Fossils ; Geography ; Geologic Sediments/*chemistry/*microbiology ; Hydrocarbons/analysis ; Lipids/analysis ; Prochlorococcus/growth & development ; Synechococcus/growth & development ; }, abstract = {Middle-to-late Ediacaran (575-541 Ma) marine sedimentary rocks record the first appearance of macroscopic, multicellular body fossils, yet little is known about the environments and food sources that sustained this enigmatic fauna. Here, we perform a lipid biomarker and stable isotope (δ[15]Ntotal and δ[13]CTOC) investigation of exceptionally immature late Ediacaran strata (<560 Ma) from multiple locations across Baltica. Our results show that the biomarker assemblages encompass an exceptionally wide range of hopane/sterane ratios (1.6-119), which is a broad measure of bacterial/eukaryotic source organism inputs. These include some unusually high hopane/sterane ratios (22-119), particularly during the peak in diversity and abundance of the Ediacara biota. A high contribution of bacteria to the overall low productivity may have bolstered a microbial loop, locally sustaining dissolved organic matter as an important organic nutrient. These oligotrophic, shallow-marine conditions extended over hundreds of kilometers across Baltica and persisted for more than 10 million years.}, } @article {pmid29725082, year = {2018}, author = {Nie, H and Jin, Z and Zhang, J}, title = {Characteristics of three organic matter pore types in the Wufeng-Longmaxi Shale of the Sichuan Basin, Southwest China.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {7014}, pmid = {29725082}, issn = {2045-2322}, mesh = {China ; Fossils/*ultrastructure ; Hydrocarbons/*analysis/chemistry ; Microalgae/chemistry ; }, abstract = {A consensus has been reached through previous studies that organic matter (OM) pores are crucial to porosity in many shale gas reservoirs; however, their origins and types remain controversial. Here, we report the OM pore types hosted in algae, bitumen, graptolite and other fossil fragments in the Wufeng-Longmaxi Formations of the Sichuan Basin, Southwest China. Algae types mainly include multicellular algae, unicellular algae, etc. The OM pores in multicellular algae usually exhibit irregular, bubble-like, spherical and/or elliptical profiles, and their diameters vary between 300 and 800 nm. The shapes of the OM pores in unicellular algae are either irregular or oval, and the pores are hundreds of nanometres in size. The pores associated with solid bitumen are sporadic, isolated and variable in size, ranging from 500 nm to 3 μm. The pores in the graptolite, sponge spicule, radiolarian and other fossil fragments are much smaller and fewer. The pores may only have developed in the surface of the graptolite and bitumen by filling in the biological cavity of the sponge spicule. These new findings provide stronger evidence that multicellular algae are the main hydrocarbon generating organisms of OM pores development.}, } @article {pmid29718307, year = {2018}, author = {Tarhan, LG and Droser, ML and Cole, DB and Gehling, JG}, title = {Ecological Expansion and Extinction in the Late Ediacaran: Weighing the Evidence for Environmental and Biotic Drivers.}, journal = {Integrative and comparative biology}, volume = {58}, number = {4}, pages = {688-702}, doi = {10.1093/icb/icy020}, pmid = {29718307}, issn = {1557-7023}, mesh = {Animals ; *Biological Evolution ; Biota ; Fossils/*anatomy & histology ; Invertebrates/*anatomy & histology/*physiology ; }, abstract = {The Ediacara Biota, Earth's earliest communities of complex, macroscopic, multicellular organisms, appeared during the late Ediacaran Period, just prior to the Cambrian Explosion. Ediacara fossil assemblages consist of exceptionally preserved soft-bodied forms of enigmatic morphology and affinity which nonetheless represent a critical stepping-stone in the evolution of complex animal ecosystems. The Ediacara Biota has historically been divided into three successive Assemblages-the Avalon, the White Sea, and the Nama. Although the oldest (Avalon) Assemblage documents the initial appearance of several groups of Ediacara taxa, the two younger (White Sea and Nama) Assemblages record a particularly striking suite of ecological innovations, including the appearance of diverse Ediacara body plans-in tandem with the rise of bilaterian animals-as well as the emergence of novel ecological strategies such as movement, sexual reproduction, biomineralization, and the development of dense, heterogeneous benthic communities. Many of these ecological innovations appear to be linked to adaptations to heterogeneous substrates and shallow and energetic marine settings. In spite of these innovations, the majority of Ediacara taxa disappear by the end of the Ediacaran, with interpretations for this disappearance historically ranging from the closing of preservational windows to environmentally or biotically mediated extinction. However, in spite of the unresolved affinity and eventual extinction of individual Ediacara taxa, these distinctive ecological strategies persist across the Ediacaran-Cambrian boundary and are characteristic of younger animal-dominated communities of the Phanerozoic. The late Ediacaran emergence of these strategies may, therefore, have facilitated subsequent radiations of the Cambrian. In this light, the Ediacaran and Cambrian Periods, although traditionally envisioned as separate worlds, are likely to have been part of an ecological and evolutionary continuum.}, } @article {pmid29717623, year = {2018}, author = {Steinbach, SK and Wang, T and Carruthers, MH and Li, A and Besla, R and Johnston, AP and Robbins, CS and Husain, M}, title = {Aortic Sca-1[+] Progenitor Cells Arise from the Somitic Mesoderm Lineage in Mice.}, journal = {Stem cells and development}, volume = {27}, number = {13}, pages = {888-897}, doi = {10.1089/scd.2018.0038}, pmid = {29717623}, issn = {1557-8534}, support = {MOP136850//CIHR/Canada ; MOP14648//CIHR/Canada ; }, mesh = {Animals ; Antigens, Ly/*metabolism ; Aorta/*metabolism ; Cell Differentiation/physiology ; Cell Lineage/*physiology ; Membrane Proteins/*metabolism ; Mesoderm/*metabolism ; Mice ; Myocytes, Smooth Muscle/metabolism ; Myogenic Regulatory Factor 5/metabolism ; SOXB1 Transcription Factors/metabolism ; Somites/*metabolism ; Stem Cells/*metabolism ; Transforming Growth Factor beta3/metabolism ; }, abstract = {Sca-1[+] progenitor cells in the adult mouse aorta are known to generate vascular smooth muscle cells (VSMCs), but their embryological origins and temporal abundance are not known. Using tamoxifen-inducible Myf5-Cre[ER] mice, we demonstrate that Sca-1[+] adult aortic cells arise from the somitic mesoderm beginning at E8.5 and continue throughout somitogenesis. Myf5 lineage-derived Sca-1[+] cells greatly expand in situ, starting at 4 weeks of age, and become a major source of aortic Sca-1[+] cells by 6 weeks of age. Myf5-derived adult aortic cells are capable of forming multicellular sphere-like structures in vitro and express the pluripotency marker Sox2. Exposure to transforming growth factor-β3 induces these spheres to differentiate into calponin-expressing VSMCs. Pulse-chase experiments using tamoxifen-inducible Sox2-Cre[ERT2] mice at 8 weeks of age demonstrate that ∼35% of all adult aortic Sca-1[+] cells are derived from Sox2[+] cells. The present study demonstrates that aortic Sca-1[+] progenitor cells are derived from the somitic mesoderm formed at the earliest stages of somitogenesis and from Sox2-expressing progenitors in adult mice.}, } @article {pmid29709110, year = {2018}, author = {Simon, CS and Hadjantonakis, AK and Schröter, C}, title = {Making lineage decisions with biological noise: Lessons from the early mouse embryo.}, journal = {Wiley interdisciplinary reviews. Developmental biology}, volume = {7}, number = {4}, pages = {e319}, pmid = {29709110}, issn = {1759-7692}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 DK084391/DK/NIDDK NIH HHS/United States ; R01 HD094868/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Blastocyst/cytology/metabolism/*physiology ; Cell Differentiation/genetics/*physiology ; Cell Lineage/genetics/physiology ; Embryo, Mammalian/cytology/embryology/metabolism ; Gene Expression Regulation, Developmental ; Mice ; *Models, Biological ; }, abstract = {Understanding how individual cells make fate decisions that lead to the faithful formation and homeostatic maintenance of tissues is a fundamental goal of contemporary developmental and stem cell biology. Seemingly uniform populations of stem cells and multipotent progenitors display a surprising degree of heterogeneity, primarily originating from the inherent stochastic nature of molecular processes underlying gene expression. Despite this heterogeneity, lineage decisions result in tissues of a defined size and with consistent proportions of differentiated cell types. Using the early mouse embryo as a model we review recent developments that have allowed the quantification of molecular intercellular heterogeneity during cell differentiation. We first discuss the relationship between these heterogeneities and developmental cellular potential. We then review recent theoretical approaches that formalize the mechanisms underlying fate decisions in the inner cell mass of the blastocyst stage embryo. These models build on our extensive knowledge of the genetic control of fate decisions in this system and will become essential tools for a rigorous understanding of the connection between noisy molecular processes and reproducible outcomes at the multicellular level. We conclude by suggesting that cell-to-cell communication provides a mechanism to exploit and buffer intercellular variability in a self-organized process that culminates in the reproducible formation of the mature mammalian blastocyst stage embryo that is ready for implantation into the maternal uterus. This article is categorized under: Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Gene Expression and Transcriptional Hierarchies > Quantitative Methods and Models.}, } @article {pmid29688518, year = {2018}, author = {Lee, J and Yang, EC and Graf, L and Yang, JH and Qiu, H and Zelzion, U and Chan, CX and Stephens, TG and Weber, APM and Boo, GH and Boo, SM and Kim, KM and Shin, Y and Jung, M and Lee, SJ and Yim, HS and Lee, JH and Bhattacharya, D and Yoon, HS}, title = {Analysis of the Draft Genome of the Red Seaweed Gracilariopsis chorda Provides Insights into Genome Size Evolution in Rhodophyta.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1869-1886}, doi = {10.1093/molbev/msy081}, pmid = {29688518}, issn = {1537-1719}, mesh = {*Biological Evolution ; DNA Methylation ; *DNA Transposable Elements ; Epigenesis, Genetic ; Gene Duplication ; Gene Expression Regulation ; *Genome Size ; Rhodophyta/*genetics ; }, abstract = {Red algae (Rhodophyta) underwent two phases of large-scale genome reduction during their early evolution. The red seaweeds did not attain genome sizes or gene inventories typical of other multicellular eukaryotes. We generated a high-quality 92.1 Mb draft genome assembly from the red seaweed Gracilariopsis chorda, including methylation and small (s)RNA data. We analyzed these and other Archaeplastida genomes to address three questions: 1) What is the role of repeats and transposable elements (TEs) in explaining Rhodophyta genome size variation, 2) what is the history of genome duplication and gene family expansion/reduction in these taxa, and 3) is there evidence for TE suppression in red algae? We find that the number of predicted genes in red algae is relatively small (4,803-13,125 genes), particularly when compared with land plants, with no evidence of polyploidization. Genome size variation is primarily explained by TE expansion with the red seaweeds having the largest genomes. Long terminal repeat elements and DNA repeats are the major contributors to genome size growth. About 8.3% of the G. chorda genome undergoes cytosine methylation among gene bodies, promoters, and TEs, and 71.5% of TEs contain methylated-DNA with 57% of these regions associated with sRNAs. These latter results suggest a role for TE-associated sRNAs in RNA-dependent DNA methylation to facilitate silencing. We postulate that the evolution of genome size in red algae is the result of the combined action of TE spread and the concomitant emergence of its epigenetic suppression, together with other important factors such as changes in population size.}, } @article {pmid29687636, year = {2018}, author = {Liu, J and Zhang, W and Du, H and Leng, X and Li, JH and Pan, H and Xu, J and Wu, LF and Xiao, T}, title = {Seasonal changes in the vertical distribution of two types of multicellular magnetotactic prokaryotes in the sediment of Lake Yuehu, China.}, journal = {Environmental microbiology reports}, volume = {10}, number = {4}, pages = {475-484}, doi = {10.1111/1758-2229.12652}, pmid = {29687636}, issn = {1758-2229}, mesh = {Ammonium Compounds/chemistry ; China ; Deltaproteobacteria/classification/cytology/genetics/*physiology ; Ferrosoferric Oxide ; Geologic Sediments/chemistry/*microbiology ; Lakes/chemistry/*microbiology ; Locomotion ; Magnetosomes/physiology ; Oxidation-Reduction ; *Seasons ; Silicates/chemistry ; }, abstract = {There are two genetically distinct morphological types of multicellular magnetotactic prokaryotes (MMPs) in the intertidal zone of Lake Yuehu (China): ellipsoidal MMPs (eMMPs) and spherical MMPs (sMMPs). We studied the vertical distribution of both types of MMPs in the sediment at Lake Yuehu during 1 year. Both types of MMPs were observed at sediment depths ranging from 1 to 34 cm, depending on the seasons. The eMMPs distributed at depths of 2-34 cm during spring, 1-11 cm during summer, 2-21 cm during autumn and 9-32 cm during winter. The eMMP species Candidatus Magnetananas rongchenensis, with magnetite magnetosomes, dominated at all distribution depths. These results suggested that Ca. M. rongchenensis migrated vertically during four seasons. The vertical profiles of oxidation-reduction potential (ORP) in Lake Yuehu changed seasonally, and these changes coincided with the seasonal distribution of MMPs, suggesting that the ORP affected the vertical distribution of MMPs. In addition, high concentrations of ammonium and silicate were associated with low abundances of MMPs.}, } @article {pmid29686411, year = {2018}, author = {Marín, I}, title = {Origin and evolution of fungal HECT ubiquitin ligases.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {6419}, pmid = {29686411}, issn = {2045-2322}, mesh = {Animals ; *Evolution, Molecular ; Genes, Fungal ; Genetic Variation ; Humans ; Saccharomyces cerevisiae/*enzymology ; Ubiquitin-Protein Ligases/genetics/*metabolism ; }, abstract = {Ubiquitin ligases (E3s) are basic components of the eukaryotic ubiquitination system. In this work, the emergence and diversification of fungal HECT ubiquitin ligases is described. Phylogenetic and structural data indicate that six HECT subfamilies (RSP5, TOM1, UFD4, HUL4, HUL4A and HUL5) existed in the common ancestor of all fungi. These six subfamilies have evolved very conservatively, with only occasional losses and duplications in particular fungal lineages. However, an early, drastic reduction in the number of HECT genes occurred in microsporidians, in parallel to the reduction of their genomes. A significant correlation between the total number of genes and the number of HECT-encoding genes present in fungi has been observed. However, transitions from unicellularity to multicellularity or vice versa apparently had no effect on the evolution of this family. Likely orthologs or co-orthologs of all fungal HECT genes have been detected in animals. Four genes are deduced to be present in the common ancestor of fungi, animals and plants. Protein-protein interactions detected in both the yeast Saccharomyces cerevisiae and humans suggest that some ancient functions of HECT proteins have been conserved since the animals/fungi split.}, } @article {pmid29686139, year = {2018}, author = {Wang, Y and Gao, Y and Li, C and Gao, H and Zhang, CC and Xu, X}, title = {Three Substrains of the Cyanobacterium Anabaena sp. Strain PCC 7120 Display Divergence in Genomic Sequences and hetC Function.}, journal = {Journal of bacteriology}, volume = {200}, number = {13}, pages = {}, pmid = {29686139}, issn = {1098-5530}, mesh = {ATP-Binding Cassette Transporters/*genetics/*metabolism ; Anabaena/*genetics/growth & development/metabolism ; Bacterial Proteins/*genetics/*metabolism ; Base Sequence ; Evolution, Molecular ; Gene Expression Regulation, Bacterial ; Genetic Variation ; Genome, Bacterial ; Genomics ; Mutation ; Polymorphism, Single Nucleotide ; Sequence Deletion ; }, abstract = {Anabaena sp. strain PCC 7120 is a model strain for molecular studies of cell differentiation and patterning in heterocyst-forming cyanobacteria. Subtle differences in heterocyst development have been noticed in different laboratories working on the same organism. In this study, 360 mutations, including single nucleotide polymorphisms (SNPs), small insertion/deletions (indels; 1 to 3 bp), fragment deletions, and transpositions, were identified in the genomes of three substrains. Heterogeneous/heterozygous bases were also identified due to the polyploidy nature of the genome and the multicellular morphology but could be completely segregated when plated after filament fragmentation by sonication. hetC is a gene upregulated in developing cells during heterocyst formation in Anabaena sp. strain PCC 7120 and found in approximately half of other heterocyst-forming cyanobacteria. Inactivation of hetC in 3 substrains of Anabaena sp. PCC 7120 led to different phenotypes: the formation of heterocysts, differentiating cells that keep dividing, or the presence of both heterocysts and dividing differentiating cells. The expression of P hetZ -gfp in these hetC mutants also showed different patterns of green fluorescent protein (GFP) fluorescence. Thus, the function of hetC is influenced by the genomic background and epistasis and constitutes an example of evolution under way.IMPORTANCE Our knowledge about the molecular genetics of heterocyst formation, an important cell differentiation process for global N2 fixation, is mostly based on studies with Anabaena sp. strain PCC 7120. Here, we show that rapid microevolution is under way in this strain, leading to phenotypic variations for certain genes related to heterocyst development, such as hetC This study provides an example for ongoing microevolution, marked by multiple heterogeneous/heterozygous single nucleotide polymorphisms (SNPs), in a multicellular multicopy-genome microorganism.}, } @article {pmid29685747, year = {2018}, author = {Miller, WB and Torday, JS}, title = {Four domains: The fundamental unicell and Post-Darwinian Cognition-Based Evolution.}, journal = {Progress in biophysics and molecular biology}, volume = {140}, number = {}, pages = {49-73}, doi = {10.1016/j.pbiomolbio.2018.04.006}, pmid = {29685747}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Cells/*cytology ; *Cognition ; Humans ; Signal Transduction ; }, abstract = {Contemporary research supports the viewpoint that self-referential cognition is the proper definition of life. From that initiating platform, a cohesive alternative evolutionary narrative distinct from standard Neodarwinism can be presented. Cognition-Based Evolution contends that biological variation is a product of a self-reinforcing information cycle that derives from self-referential attachment to biological information space-time with its attendant ambiguities. That information cycle is embodied through obligatory linkages among energy, biological information, and communication. Successive reiterations of the information cycle enact the informational architectures of the basic unicellular forms. From that base, inter-domain and cell-cell communications enable genetic and cellular variations through self-referential natural informational engineering and cellular niche construction. Holobionts are the exclusive endpoints of that self-referential cellular engineering as obligatory multicellular combinations of the essential Four Domains: Prokaryota, Archaea, Eukaryota and the Virome. Therefore, it is advocated that these Four Domains represent the perpetual object of the living circumstance rather than the visible macroorganic forms. In consequence, biology and its evolutionary development can be appraised as the continual defense of instantiated cellular self-reference. As the survival of cells is as dependent upon limitations and boundaries as upon any freedom of action, it is proposed that selection represents only one of many forms of cellular constraint that sustain self-referential integrity.}, } @article {pmid29675836, year = {2018}, author = {Nagy, LG and Kovács, GM and Krizsán, K}, title = {Complex multicellularity in fungi: evolutionary convergence, single origin, or both?.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1778-1794}, doi = {10.1111/brv.12418}, pmid = {29675836}, issn = {1469-185X}, support = {P2014/12//Hungarian Academy of Sciences/International ; ERC_HU Grant #118722//NRDI Office/International ; }, mesh = {*Biological Evolution ; Ecosystem ; Fungi/*cytology/*genetics ; Gene Expression Regulation, Fungal ; Genome, Fungal ; Genomics ; }, abstract = {Complex multicellularity represents the most advanced level of biological organization and it has evolved only a few times: in metazoans, green plants, brown and red algae and fungi. Compared to other lineages, the evolution of multicellularity in fungi follows different principles; both simple and complex multicellularity evolved via unique mechanisms not found in other lineages. Herein we review ecological, palaeontological, developmental and genomic aspects of complex multicellularity in fungi and discuss general principles of the evolution of complex multicellularity in light of its fungal manifestations. Fungi represent the only lineage in which complex multicellularity shows signatures of convergent evolution: it appears 8-11 times in distinct fungal lineages, which show a patchy phylogenetic distribution yet share some of the genetic mechanisms underlying complex multicellular development. To explain the patchy distribution of complex multicellularity across the fungal phylogeny we identify four key observations: the large number of apparently independent complex multicellular clades; the lack of documented phenotypic homology between these clades; the conservation of gene circuits regulating the onset of complex multicellular development; and the existence of clades in which the evolution of complex multicellularity is coupled with limited gene family diversification. We discuss how these patterns and known genetic aspects of fungal development can be reconciled with the genetic theory of convergent evolution to explain the pervasive occurrence of complex multicellularity across the fungal tree of life.}, } @article {pmid29675831, year = {2018}, author = {Kauko, A and Lehto, K}, title = {Eukaryote specific folds: Part of the whole.}, journal = {Proteins}, volume = {86}, number = {8}, pages = {868-881}, doi = {10.1002/prot.25517}, pmid = {29675831}, issn = {1097-0134}, mesh = {Archaea/genetics ; Bacteria/classification ; Biological Evolution ; Databases, Protein ; Eukaryota/*classification ; Eukaryotic Cells/classification ; Evolution, Molecular ; Genes, Bacterial ; Genes, Mitochondrial ; Mitochondria/genetics ; Phylogeny ; Proteins/genetics ; Symbiosis/*genetics ; }, abstract = {The origin of eukaryotes is one of the central transitions in the history of life; without eukaryotes there would be no complex multicellular life. The most accepted scenarios suggest the endosymbiosis of a mitochondrial ancestor with a complex archaeon, even though the details regarding the host and the triggering factors are still being discussed. Accordingly, phylogenetic analyses have demonstrated archaeal affiliations with key informational systems, while metabolic genes are often related to bacteria, mostly to the mitochondrial ancestor. Despite of this, there exists a large number of protein families and folds found only in eukaryotes. In this study, we have analyzed structural superfamilies and folds that probably appeared during eukaryogenesis. These folds typically represent relatively small binding domains of larger multidomain proteins. They are commonly involved in biological processes that are particularly complex in eukaryotes, such as signaling, trafficking/cytoskeleton, ubiquitination, transcription and RNA processing, but according to recent studies, these processes also have prokaryotic roots. Thus the folds originating from an eukaryotic stem seem to represent accessory parts that have contributed in the expansion of several prokaryotic processes to a new level of complexity. This might have taken place as a co-evolutionary process where increasing complexity and fold innovations have supported each other.}, } @article {pmid29663630, year = {2018}, author = {Albuquerque, TAF and Drummond do Val, L and Doherty, A and de Magalhães, JP}, title = {From humans to hydra: patterns of cancer across the tree of life.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1715-1734}, pmid = {29663630}, issn = {1469-185X}, support = {//Wellcome Trust/United Kingdom ; 104978/Z/14/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Genetic Predisposition to Disease ; Humans ; *Hydra ; *Neoplasms ; Species Specificity ; }, abstract = {Cancer is a disease of multicellularity; it originates when cells become dysregulated due to mutations and grow out of control, invading other tissues and provoking discomfort, disability, and eventually death. Human life expectancy has greatly increased in the last two centuries, and consequently so has the incidence of cancer. However, how cancer patterns in humans compare to those of other species remains largely unknown. In this review, we search for clues about cancer and its evolutionary underpinnings across the tree of life. We discuss data from a wide range of species, drawing comparisons with humans when adequate, and interpret our findings from an evolutionary perspective. We conclude that certain cancers are uniquely common in humans, such as lung, prostate, and testicular cancer; while others are common across many species. Lymphomas appear in almost every animal analysed, including in young animals, which may be related to pathogens imposing selection on the immune system. Cancers unique to humans may be due to our modern environment or may be evolutionary accidents: random events in the evolution of our species. Finally, we find that cancer-resistant animals such as whales and mole-rats have evolved cellular mechanisms that help them avoid neoplasia, and we argue that there are multiple natural routes to cancer resistance.}, } @article {pmid29662839, year = {2018}, author = {Dhakshinamoorthy, R and Bitzhenner, M and Cosson, P and Soldati, T and Leippe, M}, title = {The Saposin-Like Protein AplD Displays Pore-Forming Activity and Participates in Defense Against Bacterial Infection During a Multicellular Stage of Dictyostelium discoideum.}, journal = {Frontiers in cellular and infection microbiology}, volume = {8}, number = {}, pages = {73}, pmid = {29662839}, issn = {2235-2988}, mesh = {Animals ; Anti-Infective Agents/metabolism/pharmacology ; Bacillus megaterium/drug effects ; Bacterial Infections/*immunology ; Dictyostelium/genetics/*immunology/metabolism/*microbiology ; Gastropoda/immunology/metabolism/microbiology ; Gene Expression Profiling ; Host-Pathogen Interactions/*immunology ; *Immunity, Innate ; Ion Channels/metabolism/pharmacology ; Klebsiella pneumoniae/drug effects/pathogenicity ; Liposomes/metabolism ; Peptides/genetics/metabolism/pharmacology ; Protozoan Proteins/metabolism/pharmacology ; Recombinant Proteins ; Saposins/genetics/immunology/*metabolism/*pharmacology ; }, abstract = {Due to their archaic life style and microbivor behavior, amoebae may represent a source of antimicrobial peptides and proteins. The amoebic protozoon Dictyostelium discoideum has been a model organism in cell biology for decades and has recently also been used for research on host-pathogen interactions and the evolution of innate immunity. In the genome of D. discoideum, genes can be identified that potentially allow the synthesis of a variety of antimicrobial proteins. However, at the protein level only very few antimicrobial proteins have been characterized that may interact directly with bacteria and help in fighting infection of D. discoideum with potential pathogens. Here, we focus on a large group of gene products that structurally belong to the saposin-like protein (SAPLIP) family and which members we named provisionally Apls (amoebapore-like peptides) according to their similarity to a comprehensively studied antimicrobial and cytotoxic pore-forming protein of the protozoan parasite Entamoeba histolytica. We focused on AplD because it is the only Apl gene that is reported to be primarily transcribed further during the multicellular stages such as the mobile slug stage. Upon knock-out (KO) of the gene, aplD[-] slugs became highly vulnerable to virulent Klebsiella pneumoniae. AplD[-] slugs harbored bacterial clumps in their interior and were unable to slough off the pathogen in their slime sheath. Re-expression of AplD in aplD[-] slugs rescued the susceptibility toward K. pneumoniae. The purified recombinant protein rAplD formed pores in liposomes and was also capable of permeabilizing the membrane of live Bacillus megaterium. We propose that the multifarious Apl family of D. discoideum comprises antimicrobial effector polypeptides that are instrumental to interact with bacteria and their phospholipid membranes. The variety of its members would allow a complementary and synergistic action against a variety of microbes, which the amoeba encounters in its environment.}, } @article {pmid29644800, year = {2018}, author = {Mincarelli, L and Lister, A and Lipscombe, J and Macaulay, IC}, title = {Defining Cell Identity with Single-Cell Omics.}, journal = {Proteomics}, volume = {18}, number = {18}, pages = {e1700312}, pmid = {29644800}, issn = {1615-9861}, mesh = {Animals ; Biomarkers/*analysis ; *Cell Lineage ; Epigenomics/*methods ; Genomics/*methods ; Humans ; Metabolomics/*methods ; Phenotype ; Proteomics/*methods ; Single-Cell Analysis/*methods ; }, abstract = {Cells are a fundamental unit of life, and the ability to study the phenotypes and behaviors of individual cells is crucial to understanding the workings of complex biological systems. Cell phenotypes (epigenomic, transcriptomic, proteomic, and metabolomic) exhibit dramatic heterogeneity between and within the different cell types and states underlying cellular functional diversity. Cell genotypes can also display heterogeneity throughout an organism, in the form of somatic genetic variation-most notably in the emergence and evolution of tumors. Recent technical advances in single-cell isolation and the development of omics approaches sensitive enough to reveal these aspects of cell identity have enabled a revolution in the study of multicellular systems. In this review, we discuss the technologies available to resolve the genomes, epigenomes, transcriptomes, proteomes, and metabolomes of single cells from a wide variety of living systems.}, } @article {pmid29643333, year = {2018}, author = {Ikeda, T and Hikichi, T and Miura, H and Shibata, H and Mitsunaga, K and Yamada, Y and Woltjen, K and Miyamoto, K and Hiratani, I and Yamada, Y and Hotta, A and Yamamoto, T and Okita, K and Masui, S}, title = {Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {1387}, pmid = {29643333}, issn = {2041-1723}, mesh = {Actins/genetics/metabolism ; Animals ; Cell Differentiation ; Cellular Reprogramming/genetics ; Chromatin/*chemistry/metabolism ; Colitis, Ulcerative/*genetics/metabolism/pathology ; Disease Models, Animal ; Female ; Gene Expression Regulation ; Induced Pluripotent Stem Cells/cytology/*metabolism ; Male ; Metaplasia/*genetics/metabolism/pathology ; Mice ; Mice, Transgenic ; Neural Stem Cells/cytology/*metabolism ; Pancreas/*metabolism/pathology ; Serum Response Factor/*genetics/metabolism ; Signal Transduction ; Trans-Activators/genetics/metabolism ; }, abstract = {Multicellular organisms consist of multiple cell types. The identity of these cells is primarily maintained by cell-type-specific gene expression programs; however, mechanisms that suppress these programs are poorly defined. Here we show that serum response factor (Srf), a transcription factor that is activated by various extracellular stimuli, can repress cell-type-specific genes and promote cellular reprogramming to pluripotency. Manipulations that decrease β-actin monomer quantity result in the nuclear accumulation of Mkl1 and the activation of Srf, which downregulate cell-type-specific genes and alter the epigenetics of regulatory regions and chromatin organization. Mice overexpressing Srf exhibit various pathologies including an ulcerative colitis-like symptom and a metaplasia-like phenotype in the pancreas. Our results demonstrate an unexpected function of Srf via a mechanism by which extracellular stimuli actively destabilize cell identity and suggest Srf involvement in a wide range of diseases.}, } @article {pmid29641448, year = {2018}, author = {Zheng, S and Long, J and Liu, Z and Tao, W and Wang, D}, title = {Identification and Evolution of TGF-β Signaling Pathway Members in Twenty-Four Animal Species and Expression in Tilapia.}, journal = {International journal of molecular sciences}, volume = {19}, number = {4}, pages = {}, pmid = {29641448}, issn = {1422-0067}, mesh = {Activin Receptors, Type I/genetics/metabolism ; Animals ; *Evolution, Molecular ; Fish Proteins/*genetics/metabolism ; Phylogeny ; Receptors, Transforming Growth Factor beta/genetics/metabolism ; *Signal Transduction ; Smad4 Protein/genetics/metabolism ; Tilapia/classification/*genetics/metabolism ; Transforming Growth Factor beta/*genetics/metabolism ; }, abstract = {Transforming growth factor β (TGF-β) signaling controls diverse cellular processes during embryogenesis as well as in mature tissues of multicellular animals. Here we carried out a comprehensive analysis of TGF-β pathway members in 24 representative animal species. The appearance of the TGF-β pathway was intrinsically linked to the emergence of metazoan. The total number of TGF-β ligands, receptors, and smads changed slightly in all invertebrates and jawless vertebrates analyzed. In contrast, expansion of the pathway members, especially ligands, was observed in jawed vertebrates most likely due to the second round of whole genome duplication (2R) and additional rounds in teleosts. Duplications of TGFB2, TGFBR2, ACVR1, SMAD4 and SMAD6, which were resulted from 2R, were first isolated. Type II receptors may be originated from the ACVR2-like ancestor. Interestingly, AMHR2 was not identified in Chimaeriformes and Cypriniformes even though they had the ligand AMH. Based on transcriptome data, TGF-β ligands exhibited a tissue-specific expression especially in the heart and gonads. However, most receptors and smads were expressed in multiple tissues indicating they were shared by different ligands. Spatial and temporal expression profiles of 8 genes in gonads of different developmental stages provided a fundamental clue for understanding their important roles in sex determination and reproduction. Taken together, our findings provided a global insight into the phylogeny and expression patterns of the TGF-β pathway genes, and hence contribute to the greater understanding of their biological roles in the organism especially in teleosts.}, } @article {pmid29632261, year = {2018}, author = {Halatek, J and Brauns, F and Frey, E}, title = {Self-organization principles of intracellular pattern formation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632261}, issn = {1471-2970}, mesh = {Animals ; Caenorhabditis elegans/*genetics ; Caenorhabditis elegans Proteins/genetics ; Escherichia coli/*genetics ; Escherichia coli Proteins/genetics ; *Evolution, Molecular ; Models, Genetic ; Saccharomyces cerevisiae/*genetics ; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae/genetics ; }, abstract = {Dynamic patterning of specific proteins is essential for the spatio-temporal regulation of many important intracellular processes in prokaryotes, eukaryotes and multicellular organisms. The emergence of patterns generated by interactions of diffusing proteins is a paradigmatic example for self-organization. In this article, we review quantitative models for intracellular Min protein patterns in Escherichia coli, Cdc42 polarization in Saccharomyces cerevisiae and the bipolar PAR protein patterns found in Caenorhabditis elegans By analysing the molecular processes driving these systems we derive a theoretical perspective on general principles underlying self-organized pattern formation. We argue that intracellular pattern formation is not captured by concepts such as 'activators', 'inhibitors' or 'substrate depletion'. Instead, intracellular pattern formation is based on the redistribution of proteins by cytosolic diffusion, and the cycling of proteins between distinct conformational states. Therefore, mass-conserving reaction-diffusion equations provide the most appropriate framework to study intracellular pattern formation. We conclude that directed transport, e.g. cytosolic diffusion along an actively maintained cytosolic gradient, is the key process underlying pattern formation. Thus the basic principle of self-organization is the establishment and maintenance of directed transport by intracellular protein dynamics.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632050, year = {2018}, author = {Fidler, AL and Boudko, SP and Rokas, A and Hudson, BG}, title = {The triple helix of collagens - an ancient protein structure that enabled animal multicellularity and tissue evolution.}, journal = {Journal of cell science}, volume = {131}, number = {7}, pages = {}, pmid = {29632050}, issn = {1477-9137}, support = {R01 DK018381/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cellular Microenvironment/genetics ; Collagen Type IV/chemistry/*genetics ; *Evolution, Molecular ; Extracellular Matrix ; Protein Conformation, alpha-Helical/*genetics ; }, abstract = {The cellular microenvironment, characterized by an extracellular matrix (ECM), played an essential role in the transition from unicellularity to multicellularity in animals (metazoans), and in the subsequent evolution of diverse animal tissues and organs. A major ECM component are members of the collagen superfamily -comprising 28 types in vertebrates - that exist in diverse supramolecular assemblies ranging from networks to fibrils. Each assembly is characterized by a hallmark feature, a protein structure called a triple helix. A current gap in knowledge is understanding the mechanisms of how the triple helix encodes and utilizes information in building scaffolds on the outside of cells. Type IV collagen, recently revealed as the evolutionarily most ancient member of the collagen superfamily, serves as an archetype for a fresh view of fundamental structural features of a triple helix that underlie the diversity of biological activities of collagens. In this Opinion, we argue that the triple helix is a protein structure of fundamental importance in building the extracellular matrix, which enabled animal multicellularity and tissue evolution.}, } @article {pmid29625658, year = {2018}, author = {Padder, SA and Prasad, R and Shah, AH}, title = {Quorum sensing: A less known mode of communication among fungi.}, journal = {Microbiological research}, volume = {210}, number = {}, pages = {51-58}, doi = {10.1016/j.micres.2018.03.007}, pmid = {29625658}, issn = {1618-0623}, mesh = {Anti-Infective Agents/pharmacology ; Bacteria/drug effects/genetics ; Bacterial Physiological Phenomena ; Candida albicans/physiology ; Drug Resistance, Multiple/genetics ; Farnesol/metabolism ; Fungi/*drug effects/*physiology ; Gene Expression Regulation, Bacterial ; Gene Expression Regulation, Fungal ; Phenylethyl Alcohol/analogs & derivatives/metabolism ; Pheromones/metabolism ; Quorum Sensing/*drug effects/genetics/*physiology ; Virulence/genetics ; Volatile Organic Compounds/metabolism ; }, abstract = {Quorum sensing (QS), a density-dependent signaling mechanism of microbial cells, involves an exchange and sense of low molecular weight signaling compounds called autoinducers. With the increase in population density, the autoinducers accumulate in the extracellular environment and once their concentration reaches a threshold, many genes are either expressed or repressed. This cell density-dependent signaling mechanism enables single cells to behave as multicellular organisms and regulates different microbial behaviors like morphogenesis, pathogenesis, competence, biofilm formation, bioluminescence, etc guided by environmental cues. Initially, QS was regarded to be a specialized system of certain bacteria. The discovery of filamentation control in pathogenic polymorphic fungus Candida albicans by farnesol revealed the phenomenon of QS in fungi as well. Pathogenic microorganisms primarily regulate the expression of virulence genes using QS systems. The indirect role of QS in the emergence of multiple drug resistance (MDR) in microbial pathogens necessitates the finding of alternative antimicrobial therapies that target QS and inhibit the same. A related phenomenon of quorum sensing inhibition (QSI) performed by small inhibitor molecules called quorum sensing inhibitors (QSIs) has an ability for efficient reduction of gene expression regulated by quorum sensing. In the present review, recent advancements in the study of different fungal quorum sensing molecules (QSMs) and quorum sensing inhibitors (QSIs) of fungal origin along with their mechanism of action and/or role/s are discussed.}, } @article {pmid29619014, year = {2018}, author = {Jani, AJ and Briggs, CJ}, title = {Host and Aquatic Environment Shape the Amphibian Skin Microbiome but Effects on Downstream Resistance to the Pathogen Batrachochytrium dendrobatidis Are Variable.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {487}, pmid = {29619014}, issn = {1664-302X}, abstract = {Symbiotic microbial communities play key roles in the health and development of their multicellular hosts. Understanding why microbial communities vary among different host species or individuals is an important step toward understanding the diversity and function of the microbiome. The amphibian skin microbiome may affect resistance to the fungal pathogen Batrachochytrium dendrobatidis (Bd). Still, the factors that determine the diversity and composition of the amphibian skin microbiome, and therefore may ultimately contribute to disease resistance, are not well understood. We conducted a two-phase experiment to first test how host and environment shape the amphibian skin microbiome, and then test if the microbiome affects or is affected by Bd infection. Most lab experiments testing assembly of the amphibian skin microbiome so far have compared sterile to non-sterile environments or heavily augmented to non-augmented frogs. A goal of this study was to evaluate, in an experimental setting, realistic potential drivers of microbiome assembly that would be relevant to patterns observed in nature. We tested effects of frog genetic background (2 source populations) and 6 natural lake water sources in shaping the microbiome of the frog Rana sierrae. Water in which frogs were housed affected the microbiome in a manner that partially mimicked patterns observed in natural populations. In particular, frogs housed in water from disease-resistant populations had greater bacterial richness than frogs housed in water from populations that died out due to Bd. However, in the experiment this difference in microbiomes did not lead to differences in host mortality or rates of pathogen load increase. Frog source population also affected the microbiome and, although none of the frogs in this study showed true resistance to infection, host source population had a small effect on the rate of pathogen load increase. This difference in infection trajectories could be due to the observed differences in the microbiome, but could also be due to other traits that differ between frogs from the two populations. In addition to examining effects of the microbiome on Bd, we tested the effect of Bd infection severity on the microbiome. Specifically, we studied a time series of the microbiome over the course of infection to test if the effects of Bd on the microbiome are dependent on Bd infection severity. Although limited to a small subset of frogs, time series analysis suggested that relative abundances of several bacterial phylotypes changed as Bd loads increased through time, indicating that Bd-induced disturbance of the R. sierrae microbiome is not a binary effect but instead is dependent on infection severity. We conclude that both host and aquatic environment help shape the R. sierrae skin microbiome, with links to small changes in disease resistance in some cases, but in this study the effect of Bd on the microbiome was greater than the effect of the microbiome on Bd. Assessment of the microbiome differences between more distantly related populations than those studied here is needed to fully understand the role of the microbiome in resistance to Bd.}, } @article {pmid29616867, year = {2018}, author = {Gaiti, F and Degnan, BM and Tanurdžić, M}, title = {Long non-coding regulatory RNAs in sponges and insights into the origin of animal multicellularity.}, journal = {RNA biology}, volume = {15}, number = {6}, pages = {696-702}, pmid = {29616867}, issn = {1555-8584}, mesh = {Animals ; *Evolution, Molecular ; *Genome ; Porifera/cytology/genetics/*metabolism ; RNA, Long Noncoding/genetics/*metabolism ; }, abstract = {How animals evolved from a single-celled ancestor over 700 million years ago is poorly understood. Recent transcriptomic and chromatin analyses in the sponge Amphimedon queenslandica, a morphologically-simple representative of one of the oldest animal phyletic lineages, have shed light on what innovations in the genome and its regulation underlie the emergence of animal multicellularity. Comparisons of the regulatory genome of this sponge with those of more complex bilaterian model species and even simpler unicellular relatives have revealed that fundamental changes in genome regulatory complexity accompanied the evolution of animal multicellularity. Here, we review and discuss the results of these recent investigations by specifically focusing on the contribution of long non-coding RNAs to the evolution of the animal regulatory genome.}, } @article {pmid29614268, year = {2018}, author = {Park, B and Kim, H and Jeon, TJ}, title = {Loss of RapC causes defects in cytokinesis, cell migration, and multicellular development of Dictyostelium.}, journal = {Biochemical and biophysical research communications}, volume = {499}, number = {4}, pages = {783-789}, doi = {10.1016/j.bbrc.2018.03.223}, pmid = {29614268}, issn = {1090-2104}, mesh = {Cell Adhesion ; *Cell Movement ; Cell Shape ; *Cytokinesis ; Dictyostelium/*cytology/*growth & development/metabolism ; Phenotype ; Phylogeny ; Protozoan Proteins/chemistry/*metabolism ; Sequence Homology, Amino Acid ; rap1 GTP-Binding Proteins/chemistry ; }, abstract = {The small GTPase Ras proteins are involved in diverse cellular processes. We investigated the functions of RapC, one of 15 Ras subfamily GTPases in Dictyostelium. Loss of RapC resulted in a spread shape of cells; severe defects in cytokinesis leading to multinucleation; decrease of migration speed in chemoattractant-mediated cell migration, likely through increased cell adhesion; and aberrations in multicellular development producing abnormal multiple tips from one mound and multi-branched developmental structures. Defects in cells lacking RapC were rescued by expressing GFP-RapC in rapC null cells. Our results demonstrate that RapC, despite its high sequence homology with Rap1, plays a negative role in cell spreading and cell adhesion, in contrast to Rap1, which is a key regulator of cell adhesion and cytoskeleton rearrangement. In addition, RapC appears to have a unique function in multicellular development and is involved in tip formation from mounds. This study contributes to the understanding of Ras-mediated cellular processes.}, } @article {pmid29610072, year = {2018}, author = {Loewke, NO and Pai, S and Cordeiro, C and Black, D and King, BL and Contag, CH and Chen, B and Baer, TM and Solgaard, O}, title = {Automated Cell Segmentation for Quantitative Phase Microscopy.}, journal = {IEEE transactions on medical imaging}, volume = {37}, number = {4}, pages = {929-940}, pmid = {29610072}, issn = {1558-254X}, support = {R01 CA172895/CA/NCI NIH HHS/United States ; R01 CA182043/CA/NCI NIH HHS/United States ; T32 EB009653/EB/NIBIB NIH HHS/United States ; }, mesh = {*Algorithms ; Cell Line ; Cells, Cultured ; Cytological Techniques/*methods ; Humans ; Image Processing, Computer-Assisted/*methods ; Microscopy/*methods ; }, abstract = {Automated cell segmentation and tracking is essential for dynamic studies of cellular morphology, movement, and interactions as well as other cellular behaviors. However, accurate, automated, and easy-to-use cell segmentation remains a challenge, especially in cases of high cell densities, where discrete boundaries are not easily discernable. Here, we present a fully automated segmentation algorithm that iteratively segments cells based on the observed distribution of optical cell volumes measured by quantitative phase microscopy. By fitting these distributions to known probability density functions, we are able to converge on volumetric thresholds that enable valid segmentation cuts. Since each threshold is determined from the observed data itself, virtually no input is needed from the user. We demonstrate the effectiveness of this approach over time using six cell types that display a range of morphologies, and evaluate these cultures over a range of confluencies. Facile dynamic measures of cell mobility and function revealed unique cellular behaviors that relate to tissue origins, state of differentiation, and real-time signaling. These will improve our understanding of multicellular communication and organization.}, } @article {pmid29608173, year = {2018}, author = {Clarke, EK and Rivera Gomez, KA and Mustachi, Z and Murph, MC and Schvarzstein, M}, title = {Manipulation of Ploidy in Caenorhabditis elegans.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {133}, pages = {}, pmid = {29608173}, issn = {1940-087X}, support = {SC2 GM118275/GM/NIGMS NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; //CIHR/Canada ; }, mesh = {Animals ; Caenorhabditis elegans/*genetics ; Male ; *Ploidies ; }, abstract = {Mechanisms that involve whole genome polyploidy play important roles in development and evolution; also, an abnormal generation of tetraploid cells has been associated with both the progression of cancer and the development of drug resistance. Until now, it has not been feasible to easily manipulate the ploidy of a multicellular animal without generating mostly sterile progeny. Presented here is a simple and rapid protocol for generating tetraploid Caenorhabditis elegans animals from any diploid strain. This method allows the user to create a bias in chromosome segregation during meiosis, ultimately increasing ploidy in C. elegans. This strategy relies on the transient reduction of expression of the rec-8 gene to generate diploid gametes. A rec-8 mutant produces diploid gametes that can potentially produce tetraploids upon fertilization. This tractable scheme has been used to generate tetraploid strains carrying mutations and chromosome rearrangements to gain insight into chromosomal dynamics and interactions during pairing and synapsis in meiosis. This method is efficient for generating stable tetraploid strains without genetic markers, can be applied to any diploid strain, and can be used to derive triploid C. elegans. This straightforward method is useful for investigating other fundamental biological questions relevant to genome instability, gene dosage, biological scaling, extracellular signaling, adaptation to stress, development of resistance to drugs, and mechanisms of speciation.}, } @article {pmid29606595, year = {2018}, author = {Lherminier, P}, title = {[Informative predation: Towards a new species concept].}, journal = {Comptes rendus biologies}, volume = {341}, number = {4}, pages = {209-218}, doi = {10.1016/j.crvi.2018.02.004}, pmid = {29606595}, issn = {1768-3238}, mesh = {*Adaptation, Physiological ; Animals ; Biological Evolution ; Child ; Courtship ; Diploidy ; Female ; Fertility ; Genome ; Humans ; Male ; *Predatory Behavior ; Pregnancy ; Reproduction/genetics ; *Selection, Genetic ; }, abstract = {We distinguish two types of predations: the predation of matter-energy equals the food chain, and the informative predation is the capture of the information brought by the sexual partners. The cell or parent consumes energy and matter to grow, multiply and produce offspring. A fixed amount of resources is divided by the number of organisms, so individual growth and numerical multiplication are limited by depletion resources of the environment. Inversely, fertilization does not destroy information, but instead produces news. The information is multiplied by the number of partners and children, since each fertilization gives rise to a new genome following a combinatorial process that continues without exhaustion. The egg does not swallow the sperm to feed, but exchange good food for quality information. With the discovery of sex, that is, 1.5 Ga ago, life added soft predation to hard predation, i.e. information production within each species to matter-energy flow between species. Replicative and informative structures are subject to two competing biological constraints: replicative fidelity promotes proliferation, but limits adaptive evolution. On the contrary, the offspring of a couple obviously cannot be a copy of both partners, they are a new production, a re-production. Sexual recombination allows the exponential enrichment of the genetic diversity, thus promoting indefinite adaptive and evolutionary capacities. Evolutionary history illustrates this: the bacteria proliferate but have remained at the first purely nutritive stage in which most of the sensory functions, mobility, defense, and feeding have experienced almost no significant novelty in three billion years. Another world appeared with the sexual management of information. Sexual reproduction actually combines two functions: multiplicative by "vertical transfer" and informative by "horizontal transfer". This distinction is very common: polypus - medusa alternations, parasite multiplication cycles, the lytochal and deuterotochal parthenogenesis of aphids, and the innumerable para- and pseudo-sexual strategies of plants opportunistically combine the two modes of asexual replication and sexual combination. However, for the majority of animals and multicellular plants that produce many gametes, numerical proliferation by descendants and informative diversity by sexuality are mutually implicated, for example in the seed. The true discovery of eukaryotes may not be the "true nucleus", as their name implies, but an orderly informative function. The field of recombinations circumscribes a class of partners genetically compatible with each other, each simultaneously prey and predator of the DNA of the other. The mythical Maxwell demon capable of tracing entropy by sorting molecules according to their state does exist: each mate is the other's Maxwell's demon. While a sexless bacterium is simply divided into two cells, two sexual parents work together to produce a single offspring a time. Added to this are the burdens involved in meiosis and crossing-over, cellular diploidy, and mating. Sex produces an information gain that is paid for by a cost of energy-material, and this barter must be fair to survive. The domains of sexual intercourse are very diverse: uniparental reproduction, alternation of asexual proliferation and sexual information, self-fertilization, endogamy, exogamy, panmixis, diffuse or structured polymorphism, fertile or sterile hybridization, horizontal transfers. Each species is a recombination field between two domains, cloning and hybridization. Multiplicative descent and informative fertilization are organically distinct, but selectively associated: the information produced by the parents' sexuality favors the predation of matter-energy and therefore the proliferation of offspring, and this proliferation in turn favors the sexed producers of information. The equation specific to each species is: enough energy to proliferate, enough information to diversify. Alternatively, two other reproductive modes obtain or transmit less information at lower cost: not enough recombinations=repetitive clonal proliferation, and too many recombinations=disordered hybridization. But these marginal modes have poor prospects, as the model of the species is successfully attractive. Better discriminate to better inform. In bacteria, the exchanged and incorporated DNA segments are directly identified by the parity of the complementary strands, which determines simultaneously the similarity, the offspring, and the pairing. In eukaryotes, on the contrary, somatic growth and germinal information are segregated. During speciation, adaptive information is compacted, delocalized, codified and published to inform the species about its own state: the prezygotic relationship governs viable mating. Under the effect of sexual selection, the runaway and the reinforcement of the characters related to courtship testifies to their identifying function, which explains the paradox of the singularity and luxuriance of the sexual hypertrophies. The speciation discretizes a balanced recombination field and validates the informative relations. The species is without degree. Mates of a species recognize each other quickly and well because the logic of coding disengages from the ecological game of adaptations. The system of mate recognition has a function of cohesion and its regularity allows the adaptations of the less regular being, it is neither elitist nor normative, it is subjected neither to a level of aptitudes, nor to sexual performances, but permissive; it protects the variability and polymorphism. Two mutually irreducible relationships triggered the debate between the taxonomists who support the phyletic definition of the species by the descendance, and the proponents of the definition by interfertility. Such a taxonomic disagreement is not insurmountable, but the issue is deeper than taxonomic concepts, because these concepts relate to two different modes of evolution. According to the phyletic model, each species is a lineage passively isolated by external circumstances; on the contrary, in the sexual model each species is actively produced by an internal process of adjustment between replicative costs and informative gains. Each species develops a solution of the equation that matches material-energy expenditures with informative gains. A species concept based on a lasting relationship between these two quantities or on the limits of certain values or their equilibrium is therefore legitimate. It is this equilibrium that all couples resolve, without our formulation being as clearly as biology desires and as physics demands. Energy expenditures and informative gains in sexuality are almost impossible to measure, yet observation and experience allow an approximate ranking of the energy/information ratio. For example, endogamy is more economical, but less diversifying than exogamy, polymorphism increases information, the reinforcement of sexual isolation limits the rate of unproductive fertilization, between neighboring species hybridization allows certain genetic contributions, etc. A closed species evolves naturally towards another just as closed. On the contrary, the artificial transfer of DNA opens the species. The natural boundaries that isolate the species are easily trespassed as energy costs and constraints of sexual recognition are easily controlled; and the perspectives of manipulations are visible, whereas natural selection never anticipates and thus works blindly. Informative, artificially directed predation stimulates the evolution of species.}, } @article {pmid29602367, year = {2018}, author = {Shingleton, AW and Frankino, WA}, title = {The (ongoing) problem of relative growth.}, journal = {Current opinion in insect science}, volume = {25}, number = {}, pages = {9-19}, doi = {10.1016/j.cois.2017.10.001}, pmid = {29602367}, issn = {2214-5753}, mesh = {Animals ; Biological Evolution ; Endocrine System/physiology ; Imaginal Discs/growth & development ; Insecta/anatomy & histology/*growth & development/physiology ; Morphogenesis/*physiology ; Phenotype ; Signal Transduction ; }, abstract = {Differential growth, the phenomenon where parts of the body grow at different rates, is necessary to generate the complex morphologies of most multicellular organisms. Despite this central importance, how differential growth is regulated remains largely unknown. Recent discoveries, particularly in insects, have started to uncover the molecular-genetic and physiological mechanisms that coordinate growth among different tissues throughout the body and regulate relative growth. These discoveries suggest that growth is coordinated by a network of signals that emanate from growing tissues and central endocrine organs. Here we review these findings and discuss their implications for understanding the regulation of relative growth and the evolution of morphology.}, } @article {pmid29599012, year = {2018}, author = {Bang, C and Dagan, T and Deines, P and Dubilier, N and Duschl, WJ and Fraune, S and Hentschel, U and Hirt, H and Hülter, N and Lachnit, T and Picazo, D and Pita, L and Pogoreutz, C and Rädecker, N and Saad, MM and Schmitz, RA and Schulenburg, H and Voolstra, CR and Weiland-Bräuer, N and Ziegler, M and Bosch, TCG}, title = {Metaorganisms in extreme environments: do microbes play a role in organismal adaptation?.}, journal = {Zoology (Jena, Germany)}, volume = {127}, number = {}, pages = {1-19}, doi = {10.1016/j.zool.2018.02.004}, pmid = {29599012}, issn = {1873-2720}, mesh = {*Adaptation, Physiological/physiology ; Animals ; Ecosystem ; *Extreme Environments ; Microbiota/genetics/*physiology ; Phylogeny ; Symbiosis/physiology ; }, abstract = {From protists to humans, all animals and plants are inhabited by microbial organisms. There is an increasing appreciation that these resident microbes influence the fitness of their plant and animal hosts, ultimately forming a metaorganism consisting of a uni- or multicellular host and a community of associated microorganisms. Research on host-microbe interactions has become an emerging cross-disciplinary field. In both vertebrates and invertebrates a complex microbiome confers immunological, metabolic and behavioural benefits; conversely, its disturbance can contribute to the development of disease states. However, the molecular and cellular mechanisms controlling the interactions within a metaorganism are poorly understood and many key interactions between the associated organisms remain unknown. In this perspective article, we outline some of the issues in interspecies interactions and in particular address the question of how metaorganisms react and adapt to inputs from extreme environments such as deserts, the intertidal zone, oligothrophic seas, and hydrothermal vents.}, } @article {pmid29597064, year = {2018}, author = {Presting, GG}, title = {Centromeric retrotransposons and centromere function.}, journal = {Current opinion in genetics & development}, volume = {49}, number = {}, pages = {79-84}, doi = {10.1016/j.gde.2018.03.004}, pmid = {29597064}, issn = {1879-0380}, mesh = {Centromere/*genetics ; DNA Breaks, Double-Stranded ; Eukaryota/genetics ; *Evolution, Molecular ; Retroelements/*genetics ; Tandem Repeat Sequences/*genetics ; }, abstract = {The centromeric DNA of most multicellular eukaryotes consists of tandem repeats (TR) that bind centromere-specific proteins and act as a substrate for the efficient repair of frequent double-stranded DNA breaks. Some retrotransposons target active centromeres during integration with such specificity that they can be used to deduce current and historic centromere positions. The roles of transposons in centromere function remain incompletely understood but appear to include maintaining centromere size and increasing the repeat content of neocentromeres that lack TR. Retrotransposons are known to give rise to TR. Centromere-targeting elements thus have the potential to replace centromeric TR essentially in situ, providing a mechanism to explain the centromere paradox, that is, the presence of unrelated centromeric TRs in closely related species.}, } @article {pmid29593113, year = {2018}, author = {Nair, RR and Fiegna, F and Velicer, GJ}, title = {Indirect evolution of social fitness inequalities and facultative social exploitation.}, journal = {Proceedings. Biological sciences}, volume = {285}, number = {1875}, pages = {}, pmid = {29593113}, issn = {1471-2954}, mesh = {*Adaptation, Physiological ; *Biological Evolution ; Confidence Intervals ; Drug Resistance, Bacterial/genetics/physiology ; Gene Deletion ; Genetic Fitness/genetics/*physiology ; Genotype ; Myxococcus xanthus/genetics/*physiology ; Rifampin/metabolism ; Spores, Bacterial ; }, abstract = {Microbial genotypes with similarly high proficiency at a cooperative behaviour in genetically pure groups often exhibit fitness inequalities caused by social interaction in mixed groups. Winning competitors in this scenario have been referred to as 'cheaters' in some studies. Such interaction-specific fitness inequalities, as well as social exploitation (in which interaction between genotypes increases absolute fitness), might evolve due to selection for competitiveness at the focal behaviour or might arise non-adaptively due to pleiotropy, hitchhiking or genetic drift. The bacterium Myxococcus xanthus sporulates during cooperative development of multicellular fruiting bodies. Using M. xanthus lineages that underwent experimental evolution in allopatry without selection on sporulation, we demonstrate that interaction-specific fitness inequalities and facultative social exploitation during development readily evolved indirectly among descendant lineages. Fitness inequalities between evolved genotypes were not caused by divergence in developmental speed, as faster-developing strains were not over-represented among competition winners. In competitions between ancestors and several evolved strains, all evolved genotypes produced more spores than the ancestors, including losers of evolved-versus-evolved competitions, indicating that adaptation in non-developmental contexts pleiotropically increased competitiveness for spore production. Overall, our results suggest that fitness inequalities caused by social interaction during cooperative processes may often evolve non-adaptively in natural populations.}, } @article {pmid29590089, year = {2018}, author = {Alemany, A and Florescu, M and Baron, CS and Peterson-Maduro, J and van Oudenaarden, A}, title = {Whole-organism clone tracing using single-cell sequencing.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {108-112}, pmid = {29590089}, issn = {1476-4687}, mesh = {Animal Fins/cytology ; Animals ; Brain/cytology ; CRISPR-Cas Systems/genetics ; *Cell Lineage/genetics ; Cell Tracking/*methods ; Clone Cells/*cytology/*metabolism ; Embryonic Stem Cells/cytology/metabolism ; Eye/cytology ; Female ; Genes, Reporter/genetics ; Hematopoietic Stem Cells/cytology/metabolism ; Male ; Multipotent Stem Cells/cytology/metabolism ; Organ Specificity ; Regeneration ; Sequence Analysis/*methods ; *Single-Cell Analysis ; Transcriptome ; Whole Body Imaging ; Zebrafish/*anatomy & histology/embryology/genetics ; }, abstract = {Embryonic development is a crucial period in the life of a multicellular organism, during which limited sets of embryonic progenitors produce all cells in the adult body. Determining which fate these progenitors acquire in adult tissues requires the simultaneous measurement of clonal history and cell identity at single-cell resolution, which has been a major challenge. Clonal history has traditionally been investigated by microscopically tracking cells during development, monitoring the heritable expression of genetically encoded fluorescent proteins and, more recently, using next-generation sequencing technologies that exploit somatic mutations, microsatellite instability, transposon tagging, viral barcoding, CRISPR-Cas9 genome editing and Cre-loxP recombination. Single-cell transcriptomics provides a powerful platform for unbiased cell-type classification. Here we present ScarTrace, a single-cell sequencing strategy that enables the simultaneous quantification of clonal history and cell type for thousands of cells obtained from different organs of the adult zebrafish. Using ScarTrace, we show that a small set of multipotent embryonic progenitors generate all haematopoietic cells in the kidney marrow, and that many progenitors produce specific cell types in the eyes and brain. In addition, we study when embryonic progenitors commit to the left or right eye. ScarTrace reveals that epidermal and mesenchymal cells in the caudal fin arise from the same progenitors, and that osteoblast-restricted precursors can produce mesenchymal cells during regeneration. Furthermore, we identify resident immune cells in the fin with a distinct clonal origin from other blood cell types. We envision that similar approaches will have major applications in other experimental systems, in which the matching of embryonic clonal origin to adult cell type will ultimately allow reconstruction of how the adult body is built from a single cell.}, } @article {pmid29589089, year = {2018}, author = {Huang, C and Fu, C and Wren, JD and Wang, X and Zhang, F and Zhang, YH and Connel, SA and Chen, T and Zhang, XA}, title = {Tetraspanin-enriched microdomains regulate digitation junctions.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {75}, number = {18}, pages = {3423-3439}, pmid = {29589089}, issn = {1420-9071}, support = {CA096991/NH/NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; 13GRNT17040028//American Heart Association/International ; R01 HL137819/HL/NHLBI NIH HHS/United States ; R01 CA096991/CA/NCI NIH HHS/United States ; R01 HL132553/HL/NHLBI NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/drug effects ; Actins/metabolism ; Animals ; Antigens, CD/genetics/metabolism ; Cell Adhesion Molecules/metabolism ; Cell Line ; Cytochalasin D/pharmacology ; Dogs ; Humans ; Intercellular Junctions/*metabolism ; Madin Darby Canine Kidney Cells ; Membrane Microdomains/metabolism ; Membrane Proteins/antagonists & inhibitors/genetics/metabolism ; Microscopy, Confocal ; Tetraspanins/chemistry/*metabolism ; }, abstract = {Tetraspanins co-emerged with multi-cellular organisms during evolution and are typically localized at the cell–cell interface, [corrected] and form tetraspanin-enriched microdomains (TEMs) by associating with each other and other membrane molecules. Tetraspanins affect various biological functions, but how tetraspanins engage in multi-faceted functions at the cellular level is largely unknown. When cells interact, the membrane microextrusions at the cell-cell interfaces form dynamic, digit-like structures between cells, which we term digitation junctions (DJs). We found that (1) tetraspanins CD9, CD81, and CD82 and (2) TEM-associated molecules integrin α3β1, CD44, EWI2/PGRL, and PI-4P are present in DJs of epithelial, endothelial, and cancer cells. Tetraspanins and their associated molecules also regulate the formation and development of DJs. Moreover, (1) actin cytoskeleton, RhoA, and actomyosin activities and (2) growth factor receptor-Src-MAP kinase signaling, but not PI-3 kinase, regulate DJs. Finally, we showed that DJs consist of various forms in different cells. Thus, DJs are common, interactive structures between cells, and likely affect cell adhesion, migration, and communication. TEMs probably modulate various cell functions through DJs. Our findings highlight that DJ morphogenesis reflects the transition between cell-matrix adhesion and cell-cell adhesion and involves both cell-cell and cell-matrix adhesion molecules.}, } @article {pmid29587819, year = {2018}, author = {Dickson, LB and Ghozlane, A and Volant, S and Bouchier, C and Ma, L and Vega-Rúa, A and Dusfour, I and Jiolle, D and Paupy, C and Mayanja, MN and Kohl, A and Lutwama, JJ and Duong, V and Lambrechts, L}, title = {Diverse laboratory colonies of Aedes aegypti harbor the same adult midgut bacterial microbiome.}, journal = {Parasites & vectors}, volume = {11}, number = {1}, pages = {207}, pmid = {29587819}, issn = {1756-3305}, support = {ANR-10-LABX-62-IBEID//Investissement d'Avenir program Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases/International ; ANR-16-CE35-0004-01//Agence Nationale de la Recherche/International ; ANR-17-ERC2-0016-01//Agence Nationale de la Recherche/International ; 734584//European Union's Horizon 2020 research and innovation programme under ZikaPLAN/International ; MC_UU_12014/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_12014/8/MRC_/Medical Research Council/United Kingdom ; MC_UU_12014/MRC_/Medical Research Council/United Kingdom ; ANR10-INBS-09-08//France Génomique consortium/International ; 2015-FED-192//Programme Opérationnel FEDER-Guadeloupe-Conseil Régional/International ; }, mesh = {Aedes/*microbiology ; Animals ; Bacteria/*classification/*genetics ; Cluster Analysis ; DNA, Ribosomal/chemistry/genetics ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Metagenomics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Host-associated microbes, collectively known as the microbiota, play an important role in the biology of multicellular organisms. In mosquito vectors of human pathogens, the gut bacterial microbiota influences vectorial capacity and has become the subject of intense study. In laboratory studies of vector biology, genetic effects are often inferred from differences between geographically and genetically diverse colonies of mosquitoes that are reared in the same insectary. It is unclear, however, to what extent genetic effects can be confounded by uncontrolled differences in the microbiota composition among mosquito colonies. To address this question, we used 16S metagenomics to compare the midgut bacterial microbiome of six laboratory colonies of Aedes aegypti recently derived from wild populations representing the geographical range and genetic diversity of the species.

RESULTS: We found that the diversity, abundance, and community structure of the midgut bacterial microbiome was remarkably similar among the six different colonies of Ae. aegypti, regardless of their geographical origin. We also confirmed the relatively low complexity of bacterial communities inhabiting the mosquito midgut.

CONCLUSIONS: Our finding that geographically diverse colonies of Ae. aegypti reared in the same insectary harbor a similar gut bacterial microbiome supports the conclusion that the gut microbiota of adult mosquitoes is environmentally determined regardless of the host genotype. Thus, uncontrolled differences in microbiota composition are unlikely to represent a significant confounding factor in genetic studies of vector biology.}, } @article {pmid29581530, year = {2018}, author = {Lin, W and Zhang, W and Zhao, X and Roberts, AP and Paterson, GA and Bazylinski, DA and Pan, Y}, title = {Genomic expansion of magnetotactic bacteria reveals an early common origin of magnetotaxis with lineage-specific evolution.}, journal = {The ISME journal}, volume = {12}, number = {6}, pages = {1508-1519}, pmid = {29581530}, issn = {1751-7370}, mesh = {Bacteria/*genetics ; Ferrosoferric Oxide/*metabolism ; Genome, Bacterial ; Iron ; Likelihood Functions ; Magnetics ; Magnetosomes/*chemistry ; Metagenome ; *Metagenomics ; Multigene Family ; *Phylogeny ; Proteobacteria/genetics ; Sulfides ; }, abstract = {The origin and evolution of magnetoreception, which in diverse prokaryotes and protozoa is known as magnetotaxis and enables these microorganisms to detect Earth's magnetic field for orientation and navigation, is not well understood in evolutionary biology. The only known prokaryotes capable of sensing the geomagnetic field are magnetotactic bacteria (MTB), motile microorganisms that biomineralize intracellular, membrane-bounded magnetic single-domain crystals of either magnetite (Fe3O4) or greigite (Fe3S4) called magnetosomes. Magnetosomes are responsible for magnetotaxis in MTB. Here we report the first large-scale metagenomic survey of MTB from both northern and southern hemispheres combined with 28 genomes from uncultivated MTB. These genomes expand greatly the coverage of MTB in the Proteobacteria, Nitrospirae, and Omnitrophica phyla, and provide the first genomic evidence of MTB belonging to the Zetaproteobacteria and "Candidatus Lambdaproteobacteria" classes. The gene content and organization of magnetosome gene clusters, which are physically grouped genes that encode proteins for magnetosome biosynthesis and organization, are more conserved within phylogenetically similar groups than between different taxonomic lineages. Moreover, the phylogenies of core magnetosome proteins form monophyletic clades. Together, these results suggest a common ancient origin of iron-based (Fe3O4 and Fe3S4) magnetotaxis in the domain Bacteria that underwent lineage-specific evolution, shedding new light on the origin and evolution of biomineralization and magnetotaxis, and expanding significantly the phylogenomic representation of MTB.}, } @article {pmid29579574, year = {2018}, author = {Lower, SS and McGurk, MP and Clark, AG and Barbash, DA}, title = {Satellite DNA evolution: old ideas, new approaches.}, journal = {Current opinion in genetics & development}, volume = {49}, number = {}, pages = {70-78}, pmid = {29579574}, issn = {1879-0380}, support = {F32 GM126736/GM/NIGMS NIH HHS/United States ; R01 GM119125/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Sequence/*genetics ; Chromosome Segregation/genetics ; DNA, Satellite/*genetics ; Eukaryota/*genetics ; *Evolution, Molecular ; Genome/genetics ; Reproductive Isolation ; }, abstract = {A substantial portion of the genomes of most multicellular eukaryotes consists of large arrays of tandemly repeated sequence, collectively called satellite DNA. The processes generating and maintaining different satellite DNA abundances across lineages are important to understand as satellites have been linked to chromosome mis-segregation, disease phenotypes, and reproductive isolation between species. While much theory has been developed to describe satellite evolution, empirical tests of these models have fallen short because of the challenges in assessing satellite repeat regions of the genome. Advances in computational tools and sequencing technologies now enable identification and quantification of satellite sequences genome-wide. Here, we describe some of these tools and how their applications are furthering our knowledge of satellite evolution and function.}, } @article {pmid29575407, year = {2018}, author = {Radzvilavicius, AL and Blackstone, NW}, title = {The evolution of individuality revisited.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1620-1633}, doi = {10.1111/brv.12412}, pmid = {29575407}, issn = {1469-185X}, mesh = {Animals ; *Biological Evolution ; Eukaryota ; Genetic Variation ; *Individuality ; *Models, Biological ; }, abstract = {Evolutionary theory is formulated in terms of individuals that carry heritable information and are subject to selective pressures. However, individuality itself is a trait that had to evolve - an individual is not an indivisible entity, but a result of evolutionary processes that necessarily begin at the lower level of hierarchical organisation. Traditional approaches to biological individuality focus on cooperation and relatedness within a group, division of labour, policing mechanisms and strong selection at the higher level. Nevertheless, despite considerable theoretical progress in these areas, a full dynamical first-principles account of how new types of individuals arise is missing. To the extent that individuality is an emergent trait, the problem can be approached by recognising the importance of individuating mechanisms that are present from the very beginning of the transition, when only lower-level selection is acting. Here we review some of the most influential theoretical work on the role of individuating mechanisms in these transitions, and demonstrate how a lower-level, bottom-up evolutionary framework can be used to understand biological complexity involved in the origin of cellular life, early eukaryotic evolution, sexual life cycles and multicellular development. Some of these mechanisms inevitably stem from environmental constraints, population structure and ancestral life cycles. Others are unique to specific transitions - features of the natural history and biochemistry that are co-opted into conflict mediation. Identifying mechanisms of individuation that provide a coarse-grained description of the system's evolutionary dynamics is an important step towards understanding how biological complexity and hierarchical organisation evolves. In this way, individuality can be reconceptualised as an approximate model that with varying degrees of precision applies to a wide range of biological systems.}, } @article {pmid29575018, year = {2018}, author = {Revilla-I-Domingo, R and Simakov, O}, title = {The Diversification of Early Emerging Metazoans: A Window into the Evolution of Animal Multicellularity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {40}, number = {5}, pages = {e1800029}, doi = {10.1002/bies.201800029}, pmid = {29575018}, issn = {1521-1878}, mesh = {Animals ; *Biological Evolution ; Cnidaria/classification ; Ctenophora/classification ; Evolution, Molecular ; Germany ; Phylogeny ; Placozoa/classification ; Porifera/classification ; }, abstract = {The biannual international workshop entitled "The diversification of early emerging metazoans: A window into animal evolution?" took place at the Evangelische Akademie Tutzing, Germany, 11-14. September 2017. It was organized by Thomas Bosch (Kiel), Thomas Holstein (Heidelberg), and Ulrich Technau (Vienna), and it was sponsored by the Deutsche Forschungsgemeinschaft (DFG). The meeting gathered over 140 researchers to discuss the contribution of non-bilaterian metazoan models (Porifera, Ctenophora, Placozoa, and Cnidaria) to our understanding of: a. The evolution of metazoan developmental processes; b. Fundamental molecular mechanisms underlying metazoan features; and c. The complex interactions that animals establish with their environment.}, } @article {pmid29573204, year = {2018}, author = {Preisner, H and Habicht, J and Garg, SG and Gould, SB}, title = {Intermediate filament protein evolution and protists.}, journal = {Cytoskeleton (Hoboken, N.J.)}, volume = {75}, number = {6}, pages = {231-243}, doi = {10.1002/cm.21443}, pmid = {29573204}, issn = {1949-3592}, mesh = {Animals ; *Biological Evolution ; Eukaryotic Cells/*cytology ; *Intermediate Filaments ; Prokaryotic Cells/*cytology ; }, abstract = {Metazoans evolved from a single protist lineage. While all eukaryotes share a conserved actin and tubulin-based cytoskeleton, it is commonly perceived that intermediate filaments (IFs), including lamin, vimentin or keratin among many others, are restricted to metazoans. Actin and tubulin proteins are conserved enough to be detectable across all eukaryotic genomes using standard phylogenetic methods, but IF proteins, in contrast, are notoriously difficult to identify by such means. Since the 1950s, dozens of cytoskeletal proteins in protists have been identified that seemingly do not belong to any of the IF families described for metazoans, yet, from a structural and functional perspective fit criteria that define metazoan IF proteins. Here, we briefly review IF protein discovery in metazoans and the implications this had for the definition of this protein family. We argue that the many cytoskeletal and filament-forming proteins of protists should be incorporated into a more comprehensive picture of IF evolution by aligning it with the recent identification of lamins across the phylogenetic diversity of eukaryotic supergroups. This then brings forth the question of how the diversity of IF proteins has unfolded. The evolution of IF proteins likely represents an example of convergent evolution, which, in combination with the speed with which these cytoskeletal proteins are evolving, generated their current diversity. IF proteins did not first emerge in metazoa, but in protists. Only the emergence of cytosolic IF proteins that appear to stem from a nuclear lamin is unique to animals and coincided with the emergence of true animal multicellularity.}, } @article {pmid29564400, year = {2018}, author = {Qin, X and Zhou, C and Zerr, DM and Adler, A and Addetia, A and Yuan, S and Greninger, AL}, title = {Heterogeneous Antimicrobial Susceptibility Characteristics in Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients.}, journal = {mSphere}, volume = {3}, number = {2}, pages = {}, pmid = {29564400}, issn = {2379-5042}, abstract = {Clinical isolates of Pseudomonas aeruginosa from patients with cystic fibrosis (CF) are known to differ from those associated with non-CF hosts by colony morphology, drug susceptibility patterns, and genomic hypermutability. Pseudomonas aeruginosa isolates from CF patients have long been recognized for their overall reduced rate of antimicrobial susceptibility, but their intraclonal MIC heterogeneity has long been overlooked. Using two distinct cohorts of clinical strains (n = 224 from 56 CF patients, n = 130 from 68 non-CF patients) isolated in 2013, we demonstrated profound Etest MIC heterogeneity in CF P. aeruginosa isolates in comparison to non-CF P. aeruginosa isolates. On the basis of whole-genome sequencing of 19 CF P. aeruginosa isolates from 9 patients with heterogeneous MICs, the core genome phylogenetic tree confirmed the within-patient CF P. aeruginosa clonal lineage along with considerable coding sequence variability. No extrachromosomal DNA elements or previously characterized antibiotic resistance mutations could account for the wide divergence in antimicrobial MICs between P. aeruginosa coisolates, though many heterogeneous mutations in efflux and porin genes and their regulators were present. A unique OprD sequence was conserved among the majority of isolates of CF P. aeruginosa analyzed, suggesting a pseudomonal response to selective pressure that is common to the isolates. Genomic sequence data also suggested that CF pseudomonal hypermutability was not entirely due to mutations in mutL, mutS, and uvr. We conclude that the net effect of hundreds of adaptive mutations, both shared between clonally related isolate pairs and unshared, accounts for their highly heterogeneous MIC variances. We hypothesize that this heterogeneity is indicative of the pseudomonal syntrophic-like lifestyle under conditions of being "locked" inside a host focal airway environment for prolonged periods. IMPORTANCE Patients with cystic fibrosis endure "chronic focal infections" with a variety of microorganisms. One microorganism, Pseudomonas aeruginosa, adapts to the host and develops resistance to a wide range of antimicrobials. Interestingly, as the infection progresses, multiple isogenic strains of P. aeruginosa emerge and coexist within the airways of these patients. Despite a common parental origin, the multiple strains of P. aeruginosa develop vastly different susceptibility patterns to actively used antimicrobial agents-a phenomenon we define as "heterogeneous MICs." By sequencing pairs of P. aeruginosa isolates displaying heterogeneous MICs, we observed widespread isogenic gene lesions in drug transporters, DNA mismatch repair machinery, and many other structural or cellular functions. Coupled with the heterogeneous MICs, these genetic lesions demonstrated a symbiotic response to host selection and suggested evolution of a multicellular syntrophic bacterial lifestyle. Current laboratory standard interpretive criteria do not address the emergence of heterogeneous growth and susceptibilities in vitro with treatment implications.}, } @article {pmid29563281, year = {2018}, author = {Rodríguez-Rojas, A and Moreno-Morales, J and Mason, AJ and Rolff, J}, title = {Cationic antimicrobial peptides do not change recombination frequency in Escherichia coli.}, journal = {Biology letters}, volume = {14}, number = {3}, pages = {}, pmid = {29563281}, issn = {1744-957X}, mesh = {Antimicrobial Cationic Peptides/administration & dosage/*pharmacology ; Escherichia coli/drug effects/*genetics ; *Recombination, Genetic/drug effects ; }, abstract = {Cationic antimicrobial peptides are ubiquitous immune effectors of multicellular organisms. We previously reported, that in contrast to most of the classic antibiotics, cationic antimicrobial peptides (AMPs) do not increase mutation rates in E. coli Here, we provide new evidence showing that AMPs do not stimulate or enhance bacterial DNA recombination in the surviving fractions. Recombination accelerates evolution of antibiotic resistance. Our findings have implications for our understanding of host-microbe interactions, the evolution of innate immune defences, and shed new light on the dynamic of antimicrobial-resistance evolution.}, } @article {pmid29559848, year = {2018}, author = {Shabardina, V and Kischka, T and Kmita, H and Suzuki, Y and Makałowski, W}, title = {Environmental adaptation of Acanthamoeba castellanii and Entamoeba histolytica at genome level as seen by comparative genomic analysis.}, journal = {International journal of biological sciences}, volume = {14}, number = {3}, pages = {306-320}, pmid = {29559848}, issn = {1449-2288}, mesh = {Acanthamoeba castellanii/*genetics/*physiology ; Actins/genetics ; *Adaptation, Physiological ; *Comparative Genomic Hybridization ; Entamoeba histolytica/*genetics/*physiology ; Gene Expression ; Genes, Protozoan ; Sequence Analysis, RNA ; Transcriptome ; }, abstract = {Amoebozoans are in many aspects interesting research objects, as they combine features of single-cell organisms with complex signaling and defense systems, comparable to multicellular organisms. Acanthamoeba castellanii is a cosmopolitan species and developed diverged feeding abilities and strong anti-bacterial resistance; Entamoeba histolytica is a parasitic amoeba, who underwent massive gene loss and its genome is almost twice smaller than that of A. castellanii. Nevertheless, both species prosper, demonstrating fitness to their specific environments. Here we compare transcriptomes of A. castellanii and E. histolytica with application of orthologs' search and gene ontology to learn how different life strategies influence genome evolution and restructuring of physiology. A. castellanii demonstrates great metabolic activity and plasticity, while E. histolytica reveals several interesting features in its translational machinery, cytoskeleton, antioxidant protection, and nutritional behavior. In addition, we suggest new features in E. histolytica physiology that may explain its successful colonization of human colon and may facilitate medical research.}, } @article {pmid29557480, year = {2018}, author = {Gonçalves, DPN and Park, DM and Schmidt, TL and Werner, C}, title = {Modular peptide-functionalized gold nanorods for effective glioblastoma multicellular tumor spheroid targeting.}, journal = {Biomaterials science}, volume = {6}, number = {5}, pages = {1140-1146}, doi = {10.1039/C7BM01107E}, pmid = {29557480}, issn = {2047-4849}, mesh = {Antineoplastic Agents/*chemistry/pharmacology ; Apoptosis ; Endocytosis ; Glioblastoma/metabolism ; Gold/*chemistry ; Humans ; Metal Nanoparticles/*chemistry ; Nanotubes/*chemistry ; Neoplastic Stem Cells/*drug effects ; Nestin/chemistry ; Polyethylene Glycols/chemistry ; Spheroids, Cellular/drug effects ; Tumor Cells, Cultured ; }, abstract = {Glioblastoma multiforme (GBM) contains a population of tumor initiating stem-like cells, termed cancer stem cells (CSCs). These CSCs, which are resistant to chemo- and radiotherapy, are thought to persist after treatment and drive tumor recurrence. Thus, it is believed that the elimination of CSCs can lead to GBM remission. GBM CSCs express Nestin on their surface, and can be therefore targeted via this protein. Gold nanorods (AuNRs) functionalized with an engineered, modular peptide that recognizes Nestin (NesPEG-AuNRs) were used to target the models of solid tumors originated from human GBM CSC multicellular tumor spheroids (MCTS). In our study, we show that NesPEG-AuNRs have low cytotoxicity, are efficiently taken up by MCTS, and distribute uniformly throughout our tumor models, not only at the periphery as often seen in other nanoparticle systems. NesPEG-AuNR uptake by MCTS appears to be mediated by an energy/caveolae endocytic mechanism. Moreover, plasmon excitation of AuNRs in the near-infrared (NIR) region results in the production of localized heat. Consequently, NesPEG-AuNR cytotoxicity is only observed during NIR-irradiation in MCTS with a high intracellular AuNR content. The intracellular accumulation/diffusion of NesPEG-AuNRs and NIR-irradiation result in photothermally induced GBM CSC apoptosis and MCTS growth inhibition. In summary, these data suggest that the combination of the Nestin recognizing peptide with AuNRs contributes to better tumor accumulation/penetration, and thus in GBM CSC elimination. Moreover, due to the modularity of our peptide design, the Nestin-binding peptide sequence can be exchanged for peptides targeting other surface markers for the treatment of various types of tumors.}, } @article {pmid29556540, year = {2018}, author = {Hynson, NA and Frank, KL and Alegado, RA and Amend, AS and Arif, M and Bennett, GM and Jani, AJ and Medeiros, MCI and Mileyko, Y and Nelson, CE and Nguyen, NH and Nigro, OD and Prisic, S and Shin, S and Takagi, D and Wilson, ST and Yew, JY}, title = {Synergy among Microbiota and Their Hosts: Leveraging the Hawaiian Archipelago and Local Collaborative Networks To Address Pressing Questions in Microbiome Research.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, pmid = {29556540}, issn = {2379-5077}, support = {P30 GM114737/GM/NIGMS NIH HHS/United States ; R21 AI109293/AI/NIAID NIH HHS/United States ; }, abstract = {Despite increasing acknowledgment that microorganisms underpin the healthy functioning of basically all multicellular life, few cross-disciplinary teams address the diversity and function of microbiota across organisms and ecosystems. Our newly formed consortium of junior faculty spanning fields such as ecology and geoscience to mathematics and molecular biology from the University of Hawai'i at Mānoa aims to fill this gap. We are united in our mutual interest in advancing a new paradigm for biology that incorporates our modern understanding of the importance of microorganisms. As our first concerted research effort, we will assess the diversity and function of microbes across an entire watershed on the island of Oahu, Hawai'i. Due to its high ecological diversity across tractable areas of land and sea, Hawai'i provides a model system for the study of complex microbial communities and the processes they mediate. Owing to our diverse expertise, we will leverage this study system to advance the field of biology.}, } @article {pmid29547664, year = {2018}, author = {Zielich, J and Tzima, E and Schröder, EA and Jemel, F and Conradt, B and Lambie, EJ}, title = {Overlapping expression patterns and functions of three paralogous P5B ATPases in Caenorhabditis elegans.}, journal = {PloS one}, volume = {13}, number = {3}, pages = {e0194451}, pmid = {29547664}, issn = {1932-6203}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/classification/*genetics/metabolism ; Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/cytology/enzymology/*genetics ; Caenorhabditis elegans Proteins/*genetics/metabolism ; Cell Movement/genetics ; *Gene Expression Profiling ; *Gene Expression Regulation, Enzymologic ; Luminescent Proteins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; Mutation ; Organelles/enzymology ; Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {P5B ATPases are present in the genomes of diverse unicellular and multicellular eukaryotes, indicating that they have an ancient origin, and that they are important for cellular fitness. Inactivation of ATP13A2, one of the four human P5B ATPases, leads to early-onset Parkinson's disease (Kufor-Rakeb Syndrome). The presence of an invariant PPALP motif within the putative substrate interaction pocket of transmembrane segment M4 suggests that all P5B ATPases might have similar transport specificity; however, the identity of the transport substrate(s) remains unknown. Nematodes of the genus Caenorhabditis possess three paralogous P5B ATPase genes, catp-5, catp-6 and catp-7, which probably originated from a single ancestral gene around the time of origin of the Caenorhabditid clade. By using CRISPR/Cas9, we have systematically investigated the expression patterns, subcellular localization and biological functions of each of the P5B ATPases of C. elegans. We find that each gene has a unique expression pattern, and that some tissues express more than one P5B. In some tissues where their expression patterns overlap, different P5Bs are targeted to different subcellular compartments (e.g., early endosomes vs. plasma membrane), whereas in other tissues they localize to the same compartment (plasma membrane). We observed lysosomal co-localization between CATP-6::GFP and LMP-1::RFP in transgenic animals; however, this was an artifact of the tagged LMP-1 protein, since anti-LMP-1 antibody staining of native protein revealed that LMP-1 and CATP-6::GFP occupy different compartments. The nematode P5Bs are at least partially redundant, since we observed synthetic sterility in catp-5(0); catp-6(0) and catp-6(0) catp-7(0) double mutants. The double mutants exhibit defects in distal tip cell migration that resemble those of ina-1 (alpha integrin ortholog) and vab-3 (Pax6 ortholog) mutants, suggesting that the nematode P5Bs are required for ina-1and/or vab-3 function. This is potentially a conserved regulatory interaction, since mammalian ATP13A2, alpha integrin and Pax6 are all required for proper dopaminergic neuron function.}, } @article {pmid29546464, year = {2018}, author = {Zhang, H and Yang, X and Feng, X and Xu, H and Yang, Q and Zou, L and Yan, M and Liu, D and Su, X and Jiao, B}, title = {Chromosome-wide gene dosage rebalance may benefit tumor progression.}, journal = {Molecular genetics and genomics : MGG}, volume = {293}, number = {4}, pages = {895-906}, pmid = {29546464}, issn = {1617-4623}, support = {XDB13030400//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; No.2016FB038//Applied Basic Research Foundation of Yunnan Province/ ; No.31371502//National Natural Science Foundation of China/ ; No. GREKF15-11//Open Project from state Key Laboratory of Genetic Resources and Evolution/ ; No.GREKF14-05//Open Project from State Key Laboratory of Genetic Resources and Evolution/ ; }, mesh = {Breast Neoplasms/*genetics ; Chromosomes, Human, X/*genetics ; Female ; *Gene Dosage ; *Gene Expression Regulation, Neoplastic ; *Gene Ontology ; Humans ; MCF-7 Cells ; }, abstract = {The high-risk of tumor initiation in patients with Turner syndrome (TS) characterized by X chromosome monosomy in women has been well established and aneuploidy, defined as an abnormal number of chromosomes, is a common feature in human cancer. However, the underlying mechanisms of X chromosome aneuploidy promoting tumorigenesis remain obscure. We propose that chromosome-wide gene dosage imbalance (CDI) may serve as an important mechanism. Here, we assess the relative expression ratios of X chromosome and autosomes (expression ratios of X:AA) between tumor samples and adjacent normal samples across 16 tumor types using expression datasets from The Cancer Genome Atlas (TCGA) project. Our results show that the expression ratios of X:AA in tumor samples are frequently rebalanced to a lower level compared to those in adjacent normal samples, which is termed chromosome-wide gene dosage rebalance (CDR) thereafter. Gene ontology (GO) analysis of differentially expression genes from X chromosome reveals that downregulation of multicellularity-related genes and upregulation of unicellularity-related genes in tumors form a distinctive feature and enrichment analysis shows that downregulated genes are enriched in tumor suppressor genes, which indicate that CDR benefits tumor progression. Further experimental results prove that disturbance of X chromosome expression by knocking down of XIST in breast cancer cells, which functions in initiation phase of X chromosome inactivation (XCI), inhibits tumor progression. Our results demonstrate that the prevalent CDRs across tumor types serve as an important mechanism in promoting tumor progression, which partially explains the high risk of tumor in patients with TS and also provides a new cancer therapy from the CDR perspective.}, } @article {pmid29546391, year = {2018}, author = {Kritzer, JA and Freyzon, Y and Lindquist, S}, title = {Yeast can accommodate phosphotyrosine: v-Src toxicity in yeast arises from a single disrupted pathway.}, journal = {FEMS yeast research}, volume = {18}, number = {3}, pages = {}, pmid = {29546391}, issn = {1567-1364}, support = {F32 NS055492/NS/NINDS NIH HHS/United States ; }, mesh = {*Genes, src ; Mitogen-Activated Protein Kinases/genetics ; Peptides, Cyclic/genetics ; Phosphorylation ; Phosphotyrosine/*metabolism ; Protein-Tyrosine Kinases/genetics ; Saccharomyces cerevisiae/*genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Signal Transduction ; Tyrosine/metabolism ; }, abstract = {Tyrosine phosphorylation is a key biochemical signal that controls growth and differentiation in multicellular organisms. Saccharomyces cerevisiae and nearly all other unicellular eukaryotes lack intact phosphotyrosine signaling pathways. However, many of these organisms have primitive phosphotyrosine-binding proteins and tyrosine phosphatases, leading to the assumption that the major barrier for emergence of phosphotyrosine signaling was the negative consequences of promiscuous tyrosine kinase activity. In this work, we reveal that the classic oncogene v-Src, which phosphorylates many dozens of proteins in yeast, is toxic because it disrupts a specific spore wall remodeling pathway. Using genetic selections, we find that expression of a specific cyclic peptide, or overexpression of SMK1, a MAP kinase that controls spore wall assembly, both lead to robust growth despite a continuous high level of phosphotyrosine in the yeast proteome. Thus, minimal genetic manipulations allow yeast to tolerate high levels of phosphotyrosine. These results indicate that the introduction of tyrosine kinases within single-celled organisms may not have been a major obstacle to the evolution of phosphotyrosine signaling.}, } @article {pmid29545531, year = {2018}, author = {Moroni, M and Servin-Vences, MR and Fleischer, R and Sánchez-Carranza, O and Lewin, GR}, title = {Voltage gating of mechanosensitive PIEZO channels.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {1096}, pmid = {29545531}, issn = {2041-1723}, mesh = {Animals ; Cell Line ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; Evolution, Molecular ; Humans ; Ion Channels/genetics/*metabolism ; *Mechanotransduction, Cellular ; Mice ; Mutation, Missense ; Patch-Clamp Techniques ; Zebrafish ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage-gated mode. Mutations that cause human diseases, such as xerocytosis, profoundly shift voltage sensitivity of PIEZO1 channels toward the resting membrane potential and strongly promote voltage gating. Voltage modulation may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Older invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive, but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts.}, } @article {pmid29545511, year = {2018}, author = {Rosenberg, AB and Roco, CM and Muscat, RA and Kuchina, A and Sample, P and Yao, Z and Graybuck, LT and Peeler, DJ and Mukherjee, S and Chen, W and Pun, SH and Sellers, DL and Tasic, B and Seelig, G}, title = {Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {176-182}, pmid = {29545511}, issn = {1095-9203}, support = {R01 CA207029/CA/NCI NIH HHS/United States ; R01 NS064404/NS/NINDS NIH HHS/United States ; R21 NS086500/NS/NINDS NIH HHS/United States ; TL1 TR002318/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Brain/*growth & development ; Cell Nucleus/genetics ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Developmental ; HEK293 Cells ; Humans ; Mice ; NIH 3T3 Cells ; Neurons/metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis/*methods ; Spinal Cord/*growth & development ; *Transcriptome ; }, abstract = {To facilitate scalable profiling of single cells, we developed split-pool ligation-based transcriptome sequencing (SPLiT-seq), a single-cell RNA-seq (scRNA-seq) method that labels the cellular origin of RNA through combinatorial barcoding. SPLiT-seq is compatible with fixed cells or nuclei, allows efficient sample multiplexing, and requires no customized equipment. We used SPLiT-seq to analyze 156,049 single-nucleus transcriptomes from postnatal day 2 and 11 mouse brains and spinal cords. More than 100 cell types were identified, with gene expression patterns corresponding to cellular function, regional specificity, and stage of differentiation. Pseudotime analysis revealed transcriptional programs driving four developmental lineages, providing a snapshot of early postnatal development in the murine central nervous system. SPLiT-seq provides a path toward comprehensive single-cell transcriptomic analysis of other similarly complex multicellular systems.}, } @article {pmid29540517, year = {2018}, author = {Yu, G and Baeder, DY and Regoes, RR and Rolff, J}, title = {Predicting drug resistance evolution: insights from antimicrobial peptides and antibiotics.}, journal = {Proceedings. Biological sciences}, volume = {285}, number = {1874}, pages = {}, pmid = {29540517}, issn = {1471-2954}, support = {260986/ERC_/European Research Council/International ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Antimicrobial Cationic Peptides/*pharmacology ; Computer Simulation ; Drug Resistance, Microbial/*genetics ; *Evolution, Molecular ; Microbial Sensitivity Tests ; Models, Genetic ; }, abstract = {Antibiotic resistance constitutes one of the most pressing public health concerns. Antimicrobial peptides (AMPs) of multicellular organisms are considered part of a solution to this problem, and AMPs produced by bacteria such as colistin are last-resort drugs. Importantly, AMPs differ from many antibiotics in their pharmacodynamic characteristics. Here we implement these differences within a theoretical framework to predict the evolution of resistance against AMPs and compare it to antibiotic resistance. Our analysis of resistance evolution finds that pharmacodynamic differences all combine to produce a much lower probability that resistance will evolve against AMPs. The finding can be generalized to all drugs with pharmacodynamics similar to AMPs. Pharmacodynamic concepts are familiar to most practitioners of medical microbiology, and data can be easily obtained for any drug or drug combination. Our theoretical and conceptual framework is, therefore, widely applicable and can help avoid resistance evolution if implemented in antibiotic stewardship schemes or the rational choice of new drug candidates.}, } @article {pmid29535324, year = {2018}, author = {Mukherjee, I and Large, RR and Corkrey, R and Danyushevsky, LV}, title = {The Boring Billion, a slingshot for Complex Life on Earth.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {4432}, pmid = {29535324}, issn = {2045-2322}, mesh = {Animals ; Biological Evolution ; Geologic Sediments/*chemistry ; Oceans and Seas ; Oxygen/metabolism ; Seawater/*chemistry ; Trace Elements/*analysis ; }, abstract = {The period 1800 to 800 Ma ("Boring Billion") is believed to mark a delay in the evolution of complex life, primarily due to low levels of oxygen in the atmosphere. Earlier studies highlight the remarkably flat C, Cr isotopes and low trace element trends during the so-called stasis, caused by prolonged nutrient, climatic, atmospheric and tectonic stability. In contrast, we suggest a first-order variability of bio-essential trace element availability in the oceans by combining systematic sampling of the Proterozoic rock record with sensitive geochemical analyses of marine pyrite by LA-ICP-MS technique. We also recall that several critical biological evolutionary events, such as the appearance of eukaryotes, origin of multicellularity & sexual reproduction, and the first major diversification of eukaryotes (crown group) occurred during this period. Therefore, it appears possible that the period of low nutrient trace elements (1800-1400 Ma) caused evolutionary pressures which became an essential trigger for promoting biological innovations in the eukaryotic domain. Later periods of stress-free conditions, with relatively high nutrient trace element concentration, facilitated diversification. We propose that the "Boring Billion" was a period of sequential stepwise evolution and diversification of complex eukaryotes, triggering evolutionary pathways that made possible the later rise of micro-metazoans and their macroscopic counterparts.}, } @article {pmid29533392, year = {2018}, author = {Bennett, JM and Calosi, P and Clusella-Trullas, S and Martínez, B and Sunday, J and Algar, AC and Araújo, MB and Hawkins, BA and Keith, S and Kühn, I and Rahbek, C and Rodríguez, L and Singer, A and Villalobos, F and Ángel Olalla-Tárraga, M and Morales-Castilla, I}, title = {GlobTherm, a global database on thermal tolerances for aquatic and terrestrial organisms.}, journal = {Scientific data}, volume = {5}, number = {}, pages = {180022}, pmid = {29533392}, issn = {2052-4463}, abstract = {How climate affects species distributions is a longstanding question receiving renewed interest owing to the need to predict the impacts of global warming on biodiversity. Is climate change forcing species to live near their critical thermal limits? Are these limits likely to change through natural selection? These and other important questions can be addressed with models relating geographical distributions of species with climate data, but inferences made with these models are highly contingent on non-climatic factors such as biotic interactions. Improved understanding of climate change effects on species will require extensive analysis of thermal physiological traits, but such data are both scarce and scattered. To overcome current limitations, we created the GlobTherm database. The database contains experimentally derived species' thermal tolerance data currently comprising over 2,000 species of terrestrial, freshwater, intertidal and marine multicellular algae, plants, fungi, and animals. The GlobTherm database will be maintained and curated by iDiv with the aim to keep expanding it, and enable further investigations on the effects of climate on the distribution of life on Earth.}, } @article {pmid29524586, year = {2018}, author = {Heber-Katz, E and Messersmith, P}, title = {Drug delivery and epimorphic salamander-type mouse regeneration: A full parts and labor plan.}, journal = {Advanced drug delivery reviews}, volume = {129}, number = {}, pages = {254-261}, pmid = {29524586}, issn = {1872-8294}, support = {R01 CA180070/CA/NCI NIH HHS/United States ; R01 DE021104/DE/NIDCR NIH HHS/United States ; R01 DE021215/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; *Drug Delivery Systems ; Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & inhibitors/metabolism ; Mice ; Mice, Inbred MRL lpr ; Prolyl-Hydroxylase Inhibitors/chemistry/*pharmacology ; Regeneration/*drug effects ; Urodela/*metabolism ; }, abstract = {The capacity to regenerate entire body parts, tissues, and organs had generally been thought to be lost in evolution with very few exceptions (e.g. the liver) surviving in mammals. The discovery of the MRL mouse and the elucidation of the underlying molecular pathway centering around hypoxia inducible factor, HIF-1α, has allowed a drug and materials approach to regeneration in mice and hopefully humans. The HIF-1α pathway is ancient and permitted the transition from unicellular to multicellular organisms. Furthermore, HIF-1α and its regulation by PHDs, important oxygen sensors in the cell, provides a perfect drug target. We review the historical background of regeneration biology, the discovery of the MRL mouse, and its underlying biology, and novel approaches to drugs, targets, and delivery systems (see Fig. 1).}, } @article {pmid29520890, year = {2018}, author = {Deevi, RK and Javadi, A and McClements, J and Vohhodina, J and Savage, K and Loughrey, MB and Evergren, E and Campbell, FC}, title = {Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.}, journal = {The Journal of pathology}, volume = {244}, number = {4}, pages = {445-459}, pmid = {29520890}, issn = {1096-9896}, mesh = {Caco-2 Cells ; Cell Proliferation ; Cell Shape ; Centrosome/*enzymology ; Chromosomal Instability ; Colorectal Neoplasms/*enzymology/genetics/pathology ; Cytoskeletal Proteins/genetics/metabolism ; Humans ; *Interphase ; Neoplasm Grading ; Phenotype ; Phosphoproteins/genetics/metabolism ; Protein Kinase C/genetics/*metabolism ; Signal Transduction ; Sodium-Hydrogen Exchangers/genetics/metabolism ; }, abstract = {Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring. PKCz regulates interdependent processes that control centrosome positioning. Among these, interaction between the cytoskeletal linker protein ezrin and its binding partner NHERF1 promotes the formation of a localized cue for anchoring interphase centrosomes to the cell cortex. Perturbation of these phenomena induced different outcomes in cells with single or extra centrosomes. Defective anchoring of a single centrosome promoted bipolar spindle misorientation, multi-lumen formation, and aberrant epithelial stratification. Collectively, these disturbances induce cribriform multicellular morphology that is typical of some categories of low-grade CRC. By contrast, defective anchoring of extra centrosomes promoted multipolar spindle formation, chromosomal instability (CIN), disruption of glandular morphology, and cell outgrowth across the extracellular matrix interface characteristic of aggressive, high-grade CRC. Because PKCz enhances apical NHERF1 intensity in 3D epithelial cultures, we used an immunohistochemical (IHC) assay of apical NHERF1 intensity as an indirect readout of PKCz activity in translational studies. We show that apical NHERF1 IHC intensity is inversely associated with multipolar spindle frequency and high-grade morphology in formalin-fixed human CRC samples. To conclude, defective PKCz control of interphase centrosome anchoring may underlie distinct categories of mitotic slippage that shape the development of low- or high-grade CRC phenotypes. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.}, } @article {pmid29518979, year = {2018}, author = {Wrzesinski, K and Fey, SJ}, title = {Metabolic Reprogramming and the Recovery of Physiological Functionality in 3D Cultures in Micro-Bioreactors.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {5}, number = {1}, pages = {}, pmid = {29518979}, issn = {2306-5354}, abstract = {The recovery of physiological functionality, which is commonly seen in tissue mimetic three-dimensional (3D) cellular aggregates (organoids, spheroids, acini, etc.), has been observed in cells of many origins (primary tissues, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and immortal cell lines). This plurality and plasticity suggest that probably several basic principles promote this recovery process. The aim of this study was to identify these basic principles and describe how they are regulated so that they can be taken in consideration when micro-bioreactors are designed. Here, we provide evidence that one of these basic principles is hypoxia, which is a natural consequence of multicellular structures grown in microgravity cultures. Hypoxia drives a partial metabolic reprogramming to aerobic glycolysis and an increased anabolic synthesis. A second principle is the activation of cytoplasmic glutaminolysis for lipogenesis. Glutaminolysis is activated in the presence of hypo- or normo-glycaemic conditions and in turn is geared to the hexosamine pathway. The reducing power needed is produced in the pentose phosphate pathway, a prime function of glucose metabolism. Cytoskeletal reconstruction, histone modification, and the recovery of the physiological phenotype can all be traced to adaptive changes in the underlying cellular metabolism. These changes are coordinated by mTOR/Akt, p53 and non-canonical Wnt signaling pathways, while myc and NF-kB appear to be relatively inactive. Partial metabolic reprogramming to aerobic glycolysis, originally described by Warburg, is independent of the cell's rate of proliferation, but is interwoven with the cells abilities to execute advanced functionality needed for replicating the tissues physiological performance.}, } @article {pmid29512128, year = {2018}, author = {Flamier, A and Singh, S and Rasmussen, TP}, title = {Use of Human Embryoid Bodies for Teratology.}, journal = {Current protocols in toxicology}, volume = {75}, number = {}, pages = {13.13.1-13.13.14}, doi = {10.1002/cptx.38}, pmid = {29512128}, issn = {1934-9262}, mesh = {Embryoid Bodies/*drug effects ; Embryonic Stem Cells/drug effects ; Humans ; Pluripotent Stem Cells/drug effects ; Teratology/*methods ; Toxicity Tests/methods ; }, abstract = {Human birth defects are relatively common and can be caused by exposure to environmental teratogens or to pharmaceuticals with teratogenic activities. Human embryonic stem cells (hESCs), by virtue of their pluripotent nature, provide an excellent cellular platform for teratogen detection and risk assessment. This unit describes detailed protocols for the preparation and validation of highly pluripotent hESCs, the production of large quantities of aggregated multicellular spheroids composed of hESCs, and these spheroids' differentiation into embryoid bodies (EBs). EBs contain a variety of cells of endodermal, ectodermal, and mesodermal origin and can be subjected to compound exposure in vitro. Hence, they are useful for the detection of chemicals with teratogenic activities. Beyond describing protocols to assemble and culture EBs, this unit details methods to exploit the EB system for teratological assessment. In addition, strategies to distinguish compounds with bona fide teratogenic activity versus simple toxicity are discussed. © 2018 by John Wiley & Sons, Inc.}, } @article {pmid29507840, year = {2018}, author = {Brüwer, JD and Voolstra, CR}, title = {First insight into the viral community of the cnidarian model metaorganism Aiptasia using RNA-Seq data.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e4449}, pmid = {29507840}, issn = {2167-8359}, abstract = {Current research posits that all multicellular organisms live in symbioses with associated microorganisms and form so-called metaorganisms or holobionts. Cnidarian metaorganisms are of specific interest given that stony corals provide the foundation of the globally threatened coral reef ecosystems. To gain first insight into viruses associated with the coral model system Aiptasia (sensu Exaiptasia pallida), we analyzed an existing RNA-Seq dataset of aposymbiotic, partially populated, and fully symbiotic Aiptasia CC7 anemones with Symbiodinium. Our approach included the selective removal of anemone host and algal endosymbiont sequences and subsequent microbial sequence annotation. Of a total of 297 million raw sequence reads, 8.6 million (∼3%) remained after host and endosymbiont sequence removal. Of these, 3,293 sequences could be assigned as of viral origin. Taxonomic annotation of these sequences suggests that Aiptasia is associated with a diverse viral community, comprising 116 viral taxa covering 40 families. The viral assemblage was dominated by viruses from the families Herpesviridae (12.00%), Partitiviridae (9.93%), and Picornaviridae (9.87%). Despite an overall stable viral assemblage, we found that some viral taxa exhibited significant changes in their relative abundance when Aiptasia engaged in a symbiotic relationship with Symbiodinium. Elucidation of viral taxa consistently present across all conditions revealed a core virome of 15 viral taxa from 11 viral families, encompassing many viruses previously reported as members of coral viromes. Despite the non-random selection of viral genetic material due to the nature of the sequencing data analyzed, our study provides a first insight into the viral community associated with Aiptasia. Similarities of the Aiptasia viral community with those of corals corroborate the application of Aiptasia as a model system to study coral holobionts. Further, the change in abundance of certain viral taxa across different symbiotic states suggests a role of viruses in the algal endosymbiosis, but the functional significance of this remains to be determined.}, } @article {pmid29500366, year = {2018}, author = {Langford, MB and Outhwaite, JE and Hughes, M and Natale, DRC and Simmons, DG}, title = {Deletion of the Syncytin A receptor Ly6e impairs syncytiotrophoblast fusion and placental morphogenesis causing embryonic lethality in mice.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {3961}, pmid = {29500366}, issn = {2045-2322}, mesh = {Animals ; Antigens, Surface/*genetics ; *Cell Fusion ; Cell Proliferation/genetics ; Cells, Cultured ; Female ; GPI-Linked Proteins/*genetics ; *Genes, Lethal ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Morphogenesis ; Neovascularization, Physiologic ; Placenta/blood supply/*cytology ; Pregnancy ; Trophoblasts/*cytology ; }, abstract = {Fetal growth and survival is dependent on the elaboration and propinquity of the fetal and maternal circulations within the placenta. Central to this is the formation of the interhaemal membrane, a multi-cellular lamina facilitating exchange of oxygen, nutrients and metabolic waste products between the mother and fetus. In rodents, this cellular barrier contains two transporting layers of syncytiotrophoblast, which are multinucleated cells that form by cell-cell fusion. Previously, we reported the expression of the GPI-linked cell surface protein LY6E by the syncytial layer closest to the maternal sinusoids of the mouse placenta (syncytiotrophoblast layer I). LY6E has since been shown to be a putative receptor for the fusogenic protein responsible for fusion of syncytiotrophoblast layer I, Syncytin A. In this report, we demonstrate that LY6E is essential for the normal fusion of syncytiotrophoblast layer I, and for the proper morphogenesis of both fetal and maternal vasculatures within the placenta. Furthermore, specific inactivation of Ly6e in the epiblast, but not in placenta, is compatible with embryonic development, indicating the embryonic lethality reported for Ly6e[-/-] embryos is most likely placental in origin.}, } @article {pmid29499253, year = {2018}, author = {Wood, KE and Komarova, NL}, title = {Cooperation-based branching as a mechanism of evolutionary speciation.}, journal = {Journal of theoretical biology}, volume = {445}, number = {}, pages = {166-186}, doi = {10.1016/j.jtbi.2018.02.033}, pmid = {29499253}, issn = {1095-8541}, support = {U01 CA187956/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/*physiology ; *Biological Evolution ; Insecta/*physiology ; *Models, Biological ; *Social Behavior ; }, abstract = {When performing complex tasks, coexistence of organisms in a shared environment can be achieved by means of different strategies. For example, individuals can evolve to complete all parts of the complex task, choosing self-sufficiency over cooperation. On the other hand, they may choose to split parts of the task and share the products for mutual benefit, such that distinct groups of the organisms specialize on a subset of elementary tasks. In contrast to the existing theory of specialization and task sharing for cells in multicellular organisms (or colonies of social insects), here we describe a mechanism of evolutionary branching which is based on cooperation and division of labor, and where selection happens at the individual level. Using a class of mathematical models and the methodology of adaptive dynamics, we investigate the conditions for such branching into distinct cooperating subgroups to occur. We show that, as long as performing multiple tasks is associated with additional cost, branching occurs for a wide parameter range, and this scenario is stable against the invasion of cheaters. We hypothesize that over time, this can lead to evolutionary speciation. Examples from bacterial evolution and the connection with the Black Queen Hypothesis are discussed. It is our hope that the theory of diversification rooted in cooperation may inspire further ecological research to identify more evolutionary examples consistent with this speciation mechanism.}, } @article {pmid29487592, year = {2018}, author = {Muraille, E}, title = {Diversity Generator Mechanisms Are Essential Components of Biological Systems: The Two Queen Hypothesis.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {223}, pmid = {29487592}, issn = {1664-302X}, abstract = {Diversity is widely known to fuel adaptation and evolutionary processes and increase robustness at the population, species and ecosystem levels. The Neo-Darwinian paradigm proposes that the diversity of biological entities is the consequence of genetic changes arising spontaneously and randomly, without regard for their usefulness. However, a growing body of evidence demonstrates that the evolutionary process has shaped mechanisms, such as horizontal gene transfer mechanisms, meiosis and the adaptive immune system, which has resulted in the regulated generation of diversity among populations. Though their origins are unrelated, these diversity generator (DG) mechanisms share common functional properties. They (i) contribute to the great unpredictability of the composition and/or behavior of biological systems, (ii) favor robustness and collectivism among populations and (iii) operate mainly by manipulating the systems that control the interaction of living beings with their environment. The definition proposed here for DGs is based on these properties and can be used to identify them according to function. Interestingly, prokaryotic DGs appear to be mainly reactive, as they generate diversity in response to environmental stress. They are involved in the widely described Red Queen/arms race/Cairnsian dynamic. The emergence of multicellular organisms harboring K selection traits (longer reproductive life cycle and smaller population size) has led to the acquisition of a new class of DGs that act anticipatively to stress pressures and generate a distinct dynamic called the "White Queen" here. The existence of DGs leads to the view of evolution as a more "intelligent" and Lamarckian-like process. Their repeated selection during evolution could be a neglected example of convergent evolution and suggests that some parts of the evolutionary process are tightly constrained by ecological factors, such as the population size, the generation time and the intensity of selective pressure. The ubiquity of DGs also suggests that regulated auto-generation of diversity is a fundamental property of life.}, } @article {pmid29487180, year = {2018}, author = {Cardon, ZG and Peredo, EL and Dohnalkova, AC and Gershone, HL and Bezanilla, M}, title = {A model suite of green algae within the Scenedesmaceae for investigating contrasting desiccation tolerance and morphology.}, journal = {Journal of cell science}, volume = {131}, number = {7}, pages = {}, doi = {10.1242/jcs.212233}, pmid = {29487180}, issn = {1477-9137}, mesh = {Cell Nucleus/chemistry/genetics/ultrastructure ; Chlorophyceae/classification/*genetics/growth & development ; Chlorophyta/*genetics/growth & development/ultrastructure ; Cytokinesis/genetics ; Ecosystem ; Golgi Apparatus/chemistry/ultrastructure ; Light ; Photosynthesis/*genetics ; *Phylogeny ; Reactive Oxygen Species/metabolism ; Time-Lapse Imaging ; }, abstract = {Microscopic green algae inhabiting desert microbiotic crusts are remarkably diverse phylogenetically, and many desert lineages have independently evolved from aquatic ancestors. Here we worked with five desert and aquatic species within the family Scenedesmaceae to examine mechanisms that underlie desiccation tolerance and release of unicellular versus multicellular progeny. Live cell staining and time-lapse confocal imaging coupled with transmission electron microscopy established that the desert and aquatic species all divide by multiple (rather than binary) fission, although progeny were unicellular in three species and multicellular (joined in a sheet-like coenobium) in two. During division, Golgi complexes were localized near nuclei, and all species exhibited dynamic rotation of the daughter cell mass within the mother cell wall at cytokinesis. Differential desiccation tolerance across the five species, assessed from photosynthetic efficiency during desiccation/rehydration cycles, was accompanied by differential accumulation of intracellular reactive oxygen species (ROS) detected using a dye sensitive to intracellular ROS. Further comparative investigation will aim to understand the genetic, ultrastructural and physiological characteristics supporting unicellular versus multicellular coenobial morphology, and the ability of representatives in the Scenedesmaceae to colonize ecologically diverse, even extreme, habitats.}, } @article {pmid29475741, year = {2018}, author = {Thomas, F and Kareva, I and Raven, N and Hamede, R and Pujol, P and Roche, B and Ujvari, B}, title = {Evolved Dependence in Response to Cancer.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {269-276}, doi = {10.1016/j.tree.2018.01.012}, pmid = {29475741}, issn = {1872-8383}, mesh = {*Biological Evolution ; Eukaryota/*genetics ; Evolution, Molecular ; Neoplasms/*genetics/prevention & control/therapy ; *Selection, Genetic ; }, abstract = {Evolved dependence is a process through which one species becomes 'dependent' on another following a long evolutionary history of interaction. This happens when adaptations selected in the first species for interacting lead to fitness costs when the second species is not encountered. Evolved dependence is frequent in host-parasite interactions, where hosts may achieve a higher fitness in the presence of the parasite than in its absence. Since oncogenic manifestations are (i) ubiquitous across multicellular life, (ii) involved in parasitic-like interactions with their hosts, and (iii) have effectively driven the selection of numerous adaptations, it is possible that multicellular organisms display evolved dependence in response to oncogenic processes. We provide a comprehensive overview of the topic, including the implications for cancer prevention and treatment.}, } @article {pmid29473286, year = {2018}, author = {Xiao, M and Li, M and Reynolds, CS}, title = {Colony formation in the cyanobacterium Microcystis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1399-1420}, doi = {10.1111/brv.12401}, pmid = {29473286}, issn = {1469-185X}, mesh = {Biomass ; Cell Adhesion ; Cell Division ; Eutrophication/physiology ; Microcystis/*physiology ; }, abstract = {Morphological evolution from a unicellular to multicellular state provides greater opportunities for organisms to attain larger and more complex living forms. As the most common freshwater cyanobacterial genus, Microcystis is a unicellular microorganism, with high phenotypic plasticity, which forms colonies and blooms in lakes and reservoirs worldwide. We conducted a systematic review of field studies from the 1990s to 2017 where Microcystis was dominant. Microcystis was detected as the dominant genus in waterbodies from temperate to subtropical and tropical zones. Unicellular Microcystis spp. can be induced to form colonies by adjusting biotic and abiotic factors in laboratory. Colony formation by cell division has been induced by zooplankton filtrate, high Pb[2+] concentration, the presence of another cyanobacterium (Cylindrospermopsis raciborskii), heterotrophic bacteria, and by low temperature and light intensity. Colony formation by cell adhesion can be induced by zooplankton grazing, high Ca[2+] concentration, and microcystins. We hypothesise that single cells of all Microcystis morphospecies initially form colonies with a similar morphology to those found in the early spring. These colonies gradually change their morphology to that of M. ichthyoblabe, M. wesenbergii and M. aeruginosa with changing environmental conditions. Colony formation provides Microcystis with many ecological advantages, including adaption to varying light, sustained growth under poor nutrient supply, protection from chemical stressors and protection from grazing. These benefits represent passive tactics responding to environmental stress. Microcystis colonies form at the cost of decreased specific growth rates compared with a unicellular habit. Large colony size allows Microcystis to attain rapid floating velocities (maximum recorded for a single colony, ∼ 10.08 m h[-1]) that enable them to develop and maintain a large biomass near the surface of eutrophic lakes, where they may shade and inhibit the growth of less-buoyant species in deeper layers. Over time, accompanying species may fail to maintain viable populations, allowing Microcystis to dominate. Microcystis blooms can be controlled by artificial mixing. Microcystis colonies and non-buoyant phytoplankton will be exposed to identical light conditions if they are evenly distributed over the water column. In that case, green algae and diatoms, which generally have a higher growth rate than Microcystis, will be more successful. Under such mixing conditions, other phytoplankton taxa could recover and the dominance of Microcystis would be reduced. This review advances our understanding of the factors and mechanisms affecting Microcystis colony formation and size in the field and laboratory through synthesis of current knowledge. The main transition pathways of morphological changes in Microcystis provide an example of the phenotypic plasticity of organisms during morphological evolution from a unicellular to multicellular state. We emphasise that the mechanisms and factors influencing competition among various close morphospecies are sometimes paradoxical because these morphospecies are potentially a single species. Further work is required to clarify the colony-forming process in different Microcystis morphospecies and the seasonal variation in this process. This will allow researchers to grow laboratory cultures that more closely reflect field morphologies and to optimise artificial mixing to manage blooms more effectively.}, } @article {pmid29472284, year = {2018}, author = {Raina, JB and Eme, L and Pollock, FJ and Spang, A and Archibald, JM and Williams, TA}, title = {Symbiosis in the microbial world: from ecology to genome evolution.}, journal = {Biology open}, volume = {7}, number = {2}, pages = {}, pmid = {29472284}, issn = {2046-6390}, abstract = {The concept of symbiosis - defined in 1879 by de Bary as 'the living together of unlike organisms' - has a rich and convoluted history in biology. In part, because it questioned the concept of the individual, symbiosis fell largely outside mainstream science and has traditionally received less attention than other research disciplines. This is gradually changing. In nature organisms do not live in isolation but rather interact with, and are impacted by, diverse beings throughout their life histories. Symbiosis is now recognized as a central driver of evolution across the entire tree of life, including, for example, bacterial endosymbionts that provide insects with vital nutrients and the mitochondria that power our own cells. Symbioses between microbes and their multicellular hosts also underpin the ecological success of some of the most productive ecosystems on the planet, including hydrothermal vents and coral reefs. In November 2017, scientists working in fields spanning the life sciences came together at a Company of Biologists' workshop to discuss the origin, maintenance, and long-term implications of symbiosis from the complementary perspectives of cell biology, ecology, evolution and genomics, taking into account both model and non-model organisms. Here, we provide a brief synthesis of the fruitful discussions that transpired.}, } @article {pmid29461501, year = {2018}, author = {Żółtowska-Aksamitowska, S and Shaala, LA and Youssef, DTA and Elhady, SS and Tsurkan, MV and Petrenko, I and Wysokowski, M and Tabachnick, K and Meissner, H and Ivanenko, VN and Bechmann, N and Joseph, Y and Jesionowski, T and Ehrlich, H}, title = {First Report on Chitin in a Non-Verongiid Marine Demosponge: The Mycale euplectellioides Case.}, journal = {Marine drugs}, volume = {16}, number = {2}, pages = {}, pmid = {29461501}, issn = {1660-3397}, mesh = {Animals ; Aquatic Organisms/chemistry/*metabolism ; Biocompatible Materials/chemistry ; Biomimetics/methods ; Chitin/*chemistry/*metabolism ; Chitinases/metabolism ; Microscopy, Electron, Scanning/methods ; Porifera/*chemistry/*metabolism ; Skeleton/chemistry/metabolism ; Spectroscopy, Fourier Transform Infrared/methods ; Spectrum Analysis, Raman/methods ; Tissue Engineering/methods ; }, abstract = {Sponges (Porifera) are recognized as aquatic multicellular organisms which developed an effective biochemical pathway over millions of years of evolution to produce both biologically active secondary metabolites and biopolymer-based skeletal structures. Among marine demosponges, only representatives of the Verongiida order are known to synthetize biologically active substances as well as skeletons made of structural polysaccharide chitin. The unique three-dimensional (3D) architecture of such chitinous skeletons opens the widow for their recent applications as adsorbents, as well as scaffolds for tissue engineering and biomimetics. This study has the ambitious goal of monitoring other orders beyond Verongiida demosponges and finding alternative sources of naturally prestructured chitinous scaffolds; especially in those demosponge species which can be cultivated at large scales using marine farming conditions. Special attention has been paid to the demosponge Mycale euplectellioides(Heteroscleromorpha: Poecilosclerida: Mycalidae) collected in the Red Sea. For the first time, we present here a detailed study of the isolation of chitin from the skeleton of this sponge, as well as its identification using diverse bioanalytical tools. Calcofluor white staining, Fourier-transform Infrared Spcetcroscopy (FTIR), electrospray ionization mass spectrometry (ESI-MS), scanning electron microscopy (SEM), and fluorescence microscopy, as well as a chitinase digestion assay were applied in order to confirm with strong evidence the finding of a-chitin in the skeleton of M. euplectellioides. We suggest that the discovery of chitin within representatives of the Mycale genus is a promising step in their evaluation of these globally distributed sponges as new renewable sources for both biologically active metabolites and chitin, which are of prospective use for pharmacology and biomaterials oriented biomedicine, respectively.}, } @article {pmid29442314, year = {2018}, author = {Aruga, J and Hatayama, M}, title = {Comparative Genomics of the Zic Family Genes.}, journal = {Advances in experimental medicine and biology}, volume = {1046}, number = {}, pages = {3-26}, doi = {10.1007/978-981-10-7311-3_1}, pmid = {29442314}, issn = {0065-2598}, mesh = {Animals ; *Evolution, Molecular ; Humans ; Multigene Family/*physiology ; *Phylogeny ; Protein Domains ; Species Specificity ; *Transcription Factors/genetics/metabolism ; Zinc Fingers/*physiology ; }, abstract = {Zic family genes encode five C2H2-type zinc finger domain-containing proteins that have many roles in animal development and maintenance. Recent phylogenetic analyses showed that Zic family genes are distributed in metazoans (multicellular animals), except Porifera (sponges) and Ctenophora (comb jellies). The sequence comparisons revealed that the zinc finger domains were absolutely conserved among the Zic family genes. Zic zinc finger domains are similar to, but distinct from those of the Gli, Glis, and Nkl gene family, and these zinc finger protein families are proposed to have been derived from a common ancestor gene. The Gli-Glis-Nkl-Zic superfamily and some other eukaryotic zinc finger proteins share a tandem CWCH2 (tCWCH2) motif, a hallmark for inter-zinc finger interaction between two adjacent C2H2 zinc fingers. In Zic family proteins, there exist additional evolutionally conserved domains known as ZOC and ZFNC, both of which may have appeared before cnidarian-bilaterian divergence. Comparison of the exon-intron boundaries in the Zic zinc finger domains revealed an intron (A-intron) that was absolutely conserved in bilaterians (metazoans with bilateral symmetry) and a placozoan (a simple nonparasitic metazoan). In vertebrates, there are five to seven Zic paralogs among which Zic1, Zic2, and Zic3 are generated through a tandem gene duplication and carboxy-terminal truncation in a vertebrate common ancestor, sharing a conserved carboxy-terminal sequence. Several hypotheses have been proposed to explain the Zic family phylogeny, including their origin, unique features in the first and second zinc finger motif, evolution of the nuclear localization signal, significance of the animal taxa-selective degeneration, gene multiplication in the vertebrate lineage, and involvement in the evolutionary alteration of the animal body plan.}, } @article {pmid29440299, year = {2018}, author = {Simonini, S and Stephenson, P and Østergaard, L}, title = {A molecular framework controlling style morphology in Brassicaceae.}, journal = {Development (Cambridge, England)}, volume = {145}, number = {5}, pages = {}, pmid = {29440299}, issn = {1477-9129}, support = {BBS/E/J/000PR9788/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M004112/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/J/000PR9773/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/J/00000613/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J004588/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P013511/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Brassicaceae/*genetics/*growth & development ; Flowers/anatomy & histology/*genetics/*growth & development ; Gene Expression Regulation, Developmental/drug effects ; Gene Expression Regulation, Plant/drug effects ; Indoleacetic Acids/pharmacology ; Phenotype ; Plant Development/drug effects/*genetics ; Plant Growth Regulators/pharmacology ; Plants, Genetically Modified ; Transcription Factors/physiology ; }, abstract = {Organ formation in multicellular organisms depends on the coordinated activities of regulatory components that integrate developmental and hormonal cues to control gene expression and mediate cell-type specification. For example, development of the Arabidopsis gynoecium is tightly controlled by distribution and synthesis of the plant hormone auxin. The functions of several transcription factors (TFs) have been linked with auxin dynamics during gynoecium development; yet how their activities are coordinated is not known. Here, we show that five such TFs function together to ensure polarity establishment at the gynoecium apex. The auxin response factor ETTIN (ARF3; herein, ETT) is a central component of this framework. Interaction of ETT with TF partners is sensitive to the presence of auxin and our results suggest that ETT forms part of a repressive gene-regulatory complex. We show that this function is conserved between members of the Brassicaceae family and that variation in an ETT subdomain affects interaction strengths and gynoecium morphology. These results suggest that variation in affinities between conserved TFs can lead to morphological differences and thus contribute to the evolution of diverse organ shapes.}, } @article {pmid29439555, year = {2018}, author = {Kapellos, GE and Paraskeva, CA and Kalogerakis, N and Doyle, PS}, title = {Theoretical Insight into the Biodegradation of Solitary Oil Microdroplets Moving through a Water Column.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {5}, number = {1}, pages = {}, pmid = {29439555}, issn = {2306-5354}, abstract = {In the aftermath of oil spills in the sea, clouds of droplets drift into the seawater column and are carried away by sea currents. The fate of the drifting droplets is determined by natural attenuation processes, mainly dissolution into the seawater and biodegradation by oil-degrading microbial communities. Specifically, microbes have developed three fundamental strategies for accessing and assimilating oily substrates. Depending on their affinity for the oily phase and ability to proliferate in multicellular structures, microbes might either attach to the oil surface and directly uptake compounds from the oily phase, or grow suspended in the aqueous phase consuming solubilized oil, or form three-dimensional biofilms over the oil-water interface. In this work, a compound particle model that accounts for all three microbial strategies is developed for the biodegradation of solitary oil microdroplets moving through a water column. Under a set of educated hypotheses, the hydrodynamics and solute transport problems are amenable to analytical solutions and a closed-form correlation is established for the overall dissolution rate as a function of the Thiele modulus, the Biot number and other key parameters. Moreover, two coupled ordinary differential equations are formulated for the evolution of the particle size and used to investigate the impact of the dissolution and biodegradation processes on the droplet shrinking rate.}, } @article {pmid29439203, year = {2018}, author = {Mori, T and Cahn, JKB and Wilson, MC and Meoded, RA and Wiebach, V and Martinez, AFC and Helfrich, EJN and Albersmeier, A and Wibberg, D and Dätwyler, S and Keren, R and Lavy, A and Rückert, C and Ilan, M and Kalinowski, J and Matsunaga, S and Takeyama, H and Piel, J}, title = {Single-bacterial genomics validates rich and varied specialized metabolism of uncultivated Entotheonella sponge symbionts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1718-1723}, pmid = {29439203}, issn = {1091-6490}, mesh = {Animals ; Bacteria/chemistry/genetics/isolation & purification ; *Bacterial Physiological Phenomena ; Bacterial Proteins/genetics/metabolism ; Genome, Bacterial ; Genomics ; Polyketides/metabolism ; *Symbiosis ; Theonella/chemistry/*microbiology/physiology ; }, abstract = {Marine sponges are prolific sources of unique bioactive natural products. The sponge Theonella swinhoei is represented by several distinct variants with largely nonoverlapping chemistry. For the Japanese chemotype Y harboring diverse complex polyketides and peptides, we previously provided genomic and functional evidence that a single symbiont, the filamentous, multicellular organism "Candidatus Entotheonella factor," produces almost all of these compounds. To obtain further insights into the chemistry of "Entotheonella," we investigated another phylotype, "Candidatus Entotheonella serta," present in the T. swinhoei WA sponge chemotype, a source of theonellamide- and misakinolide-type compounds. Unexpectedly, considering the lower chemical diversity, sequencing of individual bacterial filaments revealed an even larger number of biosynthetic gene regions than for Ca E. factor, with virtually no overlap. These included genes for misakinolide and theonellamide biosynthesis, the latter assigned by comparative genomic and metabolic analysis of a T. swinhoei chemotype from Israel, and by biochemical studies. The data suggest that both compound families, which were among the earliest model substances to study bacterial producers in sponges, originate from the same bacterium in T. swinhoei WA. They also add evidence that metabolic richness and variability could be a more general feature of Entotheonella symbionts.}, } @article {pmid29436502, year = {2018}, author = {Hörandl, E and Speijer, D}, title = {How oxygen gave rise to eukaryotic sex.}, journal = {Proceedings. Biological sciences}, volume = {285}, number = {1872}, pages = {}, pmid = {29436502}, issn = {1471-2954}, mesh = {*Biological Evolution ; Eukaryota/*physiology ; Oxygen/*metabolism ; Reactive Oxygen Species/metabolism ; *Sex ; Symbiosis/physiology ; }, abstract = {How did full meiotic eukaryotic sex evolve and what was the immediate advantage allowing it to develop? We propose that the crucial determinant can be found in internal reactive oxygen species (ROS) formation at the start of eukaryotic evolution approximately 2 × 10[9] years ago. The large amount of ROS coming from a bacterial endosymbiont gave rise to DNA damage and vast increases in host genome mutation rates. Eukaryogenesis and chromosome evolution represent adaptations to oxidative stress. The host, an archaeon, most probably already had repair mechanisms based on DNA pairing and recombination, and possibly some kind of primitive cell fusion mechanism. The detrimental effects of internal ROS formation on host genome integrity set the stage allowing evolution of meiotic sex from these humble beginnings. Basic meiotic mechanisms thus probably evolved in response to endogenous ROS production by the 'pre-mitochondrion'. This alternative to mitosis is crucial under novel, ROS-producing stress situations, like extensive motility or phagotrophy in heterotrophs and endosymbiontic photosynthesis in autotrophs. In multicellular eukaryotes with a germline-soma differentiation, meiotic sex with diploid-haploid cycles improved efficient purging of deleterious mutations. Constant pressure of endogenous ROS explains the ubiquitous maintenance of meiotic sex in practically all eukaryotic kingdoms. Here, we discuss the relevant observations underpinning this model.}, } @article {pmid29435031, year = {2018}, author = {Al-Ramadan, A and Mortensen, AC and Carlsson, J and Nestor, MV}, title = {Analysis of radiation effects in two irradiated tumor spheroid models.}, journal = {Oncology letters}, volume = {15}, number = {3}, pages = {3008-3016}, pmid = {29435031}, issn = {1792-1074}, abstract = {Multicellular spheroids have proven suitable as three-dimensional in vivo-like models of non-vascularized micrometastases. Unlike monolayer-based models, spheroids mirror the cellular milieu and the pathophysiological gradients inside tumor nodules. However, there is limited knowledge of the radiation effects at the molecular level in spheroids of human origin. The present study is a presentation of selected cell biological processes that may easily be analyzed with methods available at routine pathology laboratories. Using gamma irradiated pancreatic neuroendocrine BON1 and colonic adenocarcinoma HCT116 spheroids as model systems, the present study assessed the radiobiological response in these models. Spheroid growth after irradiation was followed over time and molecular responses were subsequently assessed with immunohistochemistry (IHC) staining for descriptive analyses and semi-automatic grading of apoptosis, G2-phase and senescence in thin sections of the spheroids. Growth studies demonstrated the BON1 spheroids were slower growing and less sensitive to radiation compared with the HCT116 spheroids. IHC staining for G2-phase was primarily observed in the outer viable P-cell layers of the spheroids, with the 6 Gy irradiated HCT116 spheroids demonstrating a very clear increase in staining intensity compared with unirradiated spheroids. Apoptosis staining results indicated increased apoptosis with increasing radiation doses. No clear association between senescence and radiation exposure in the spheroids were observed. The present results demonstrate the feasibility of the use of multicellular spheroids of human origin in combination with IHC analyses to unravel radiobiological responses at a molecular level. The present findings inspire further investigations, including other relevant IHC-detectable molecular processes in time- and radiation dose-dependent settings.}, } @article {pmid29432421, year = {2018}, author = {Exposito-Alonso, M and Becker, C and Schuenemann, VJ and Reiter, E and Setzer, C and Slovak, R and Brachi, B and Hagmann, J and Grimm, DG and Chen, J and Busch, W and Bergelson, J and Ness, RW and Krause, J and Burbano, HA and Weigel, D}, title = {The rate and potential relevance of new mutations in a colonizing plant lineage.}, journal = {PLoS genetics}, volume = {14}, number = {2}, pages = {e1007155}, pmid = {29432421}, issn = {1553-7404}, mesh = {Arabidopsis/genetics/growth & development ; Crosses, Genetic ; Directed Molecular Evolution ; Evolution, Molecular ; Gene Flow/physiology ; *Genome, Plant ; Introduced Species ; Mutation/*physiology ; *Mutation Rate ; Phenotype ; Phylogeny ; Plant Development/*genetics ; Plant Weeds/genetics/growth & development ; Selection, Genetic ; Sequence Analysis, DNA ; }, abstract = {By following the evolution of populations that are initially genetically homogeneous, much can be learned about core biological principles. For example, it allows for detailed studies of the rate of emergence of de novo mutations and their change in frequency due to drift and selection. Unfortunately, in multicellular organisms with generation times of months or years, it is difficult to set up and carry out such experiments over many generations. An alternative is provided by "natural evolution experiments" that started from colonizations or invasions of new habitats by selfing lineages. With limited or missing gene flow from other lineages, new mutations and their effects can be easily detected. North America has been colonized in historic times by the plant Arabidopsis thaliana, and although multiple intercrossing lineages are found today, many of the individuals belong to a single lineage, HPG1. To determine in this lineage the rate of substitutions-the subset of mutations that survived natural selection and drift-, we have sequenced genomes from plants collected between 1863 and 2006. We identified 73 modern and 27 herbarium specimens that belonged to HPG1. Using the estimated substitution rate, we infer that the last common HPG1 ancestor lived in the early 17th century, when it was most likely introduced by chance from Europe. Mutations in coding regions are depleted in frequency compared to those in other portions of the genome, consistent with purifying selection. Nevertheless, a handful of mutations is found at high frequency in present-day populations. We link these to detectable phenotypic variance in traits of known ecological importance, life history and growth, which could reflect their adaptive value. Our work showcases how, by applying genomics methods to a combination of modern and historic samples from colonizing lineages, we can directly study new mutations and their potential evolutionary relevance.}, } @article {pmid29432146, year = {2018}, author = {Simonet, P and Gaget, K and Balmand, S and Ribeiro Lopes, M and Parisot, N and Buhler, K and Duport, G and Vulsteke, V and Febvay, G and Heddi, A and Charles, H and Callaerts, P and Calevro, F}, title = {Bacteriocyte cell death in the pea aphid/Buchnera symbiotic system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1819-E1828}, pmid = {29432146}, issn = {1091-6490}, mesh = {Animals ; Aphids/*microbiology ; Buchnera/*physiology ; Cell Death ; Lysosomes ; Symbiosis/*physiology ; }, abstract = {Symbiotic associations play a pivotal role in multicellular life by facilitating acquisition of new traits and expanding the ecological capabilities of organisms. In insects that are obligatorily dependent on intracellular bacterial symbionts, novel host cells (bacteriocytes) or organs (bacteriomes) have evolved for harboring beneficial microbial partners. The processes regulating the cellular life cycle of these endosymbiont-bearing cells, such as the cell-death mechanisms controlling their fate and elimination in response to host physiology, are fundamental questions in the biology of symbiosis. Here we report the discovery of a cell-death process involved in the degeneration of bacteriocytes in the hemipteran insect Acyrthosiphon pisum This process is activated progressively throughout aphid adulthood and exhibits morphological features distinct from known cell-death pathways. By combining electron microscopy, immunohistochemistry, and molecular analyses, we demonstrated that the initial event of bacteriocyte cell death is the cytoplasmic accumulation of nonautophagic vacuoles, followed by a sequence of cellular stress responses including the formation of autophagosomes in intervacuolar spaces, activation of reactive oxygen species, and Buchnera endosymbiont degradation by the lysosomal system. We showed that this multistep cell-death process originates from the endoplasmic reticulum, an organelle exhibiting a unique reticular network organization spread throughout the entire cytoplasm and surrounding Buchnera aphidicola endosymbionts. Our findings provide insights into the cellular and molecular processes that coordinate eukaryotic host and endosymbiont homeostasis and death in a symbiotic system and shed light on previously unknown aspects of bacteriocyte biological functioning.}, } @article {pmid29427837, year = {2018}, author = {Baldauf, SL and Romeralo, M and Fiz-Palacios, O and Heidari, N}, title = {A Deep Hidden Diversity of Dictyostelia.}, journal = {Protist}, volume = {169}, number = {1}, pages = {64-78}, doi = {10.1016/j.protis.2017.12.005}, pmid = {29427837}, issn = {1618-0941}, mesh = {*Biodiversity ; DNA Primers/genetics ; DNA, Protozoan/genetics ; DNA, Ribosomal/genetics ; Dictyostelium/classification/*genetics/isolation & purification ; Phylogeny ; Polymerase Chain Reaction ; }, abstract = {Dictyostelia is a monophyletic group of transiently multicellular (sorocarpic) amoebae, whose study is currently limited to laboratory culture. This tends to favour faster growing species with robust sorocarps, while species with smaller more delicate sorocarps constitute most of the group's taxonomic breadth. The number of known species is also small (∼150) given Dictyostelia's molecular depth and apparent antiquity (>600 myr). Nonetheless, dictyostelid sequences are rarely recovered in culture independent sampling (ciPCR) surveys. We developed ciPCR primers to specifically target dictyostelid small subunit (SSU or 18S) rDNA and tested them on total DNAs extracted from a wide range of soils from five continents. The resulting clone libraries show mostly dictyostelid sequences (∼90%), and phylogenetic analyses of these sequences indicate novel lineages in all four dictyostelid families and most genera. This is especially true for the species-rich Heterostelium and Dictyosteliaceae but also the less species-rich Raperosteliaceae. However, the most novel deep branches are found in two very species-poor taxa, including the deepest branch yet seen in the highly divergent Cavenderiaceae. These results confirm a deep hidden diversity of Dictyostelia, potentially including novel morphologies and developmental schemes. The primers and protocols presented here should also enable more comprehensive studies of dictyostelid ecology.}, } @article {pmid29425731, year = {2018}, author = {Israel, MR and Morgan, M and Tay, B and Deuis, JR}, title = {Toxins as tools: Fingerprinting neuronal pharmacology.}, journal = {Neuroscience letters}, volume = {679}, number = {}, pages = {4-14}, doi = {10.1016/j.neulet.2018.02.001}, pmid = {29425731}, issn = {1872-7972}, mesh = {Animals ; Behavior Rating Scale ; Electrophysiology/methods ; Humans ; Ion Channel Gating/drug effects ; Ion Channels/chemistry/metabolism/pharmacology ; Models, Animal ; Neurons/*drug effects/physiology ; Neuropharmacology/*methods ; Neurotoxins/*pharmacology/*therapeutic use ; Sensory Receptor Cells/chemistry/*metabolism ; }, abstract = {Toxins have been used as tools for decades to study the structure and function of neuronal ion channels and receptors. The biological origin of these toxins varies from single cell organisms, including bacteria and algae, to complex multicellular organisms, including a wide variety of plants and venomous animals. Toxins are a structurally and functionally diverse group of compounds that often modulate neuronal function by interacting with an ion channel or receptor. Many of these toxins display high affinity and exquisite selectivity, making them valuable tools to probe the structure and function of neuronal ion channels and receptors. This review article provides an overview of the experimental techniques used to assess the effects that toxins have on neuronal function, as well as discussion on toxins that have been used as tools, with a focus on toxins that target voltage-gated and ligand-gated ion channels.}, } @article {pmid29424391, year = {2018}, author = {Cipriano, JLD and Cruz, ACF and Mancini, KC and Schmildt, ER and Lopes, JC and Otoni, WC and Alexandre, RS}, title = {Somatic embryogenesis in Carica papaya as affected by auxins and explants, and morphoanatomical-related aspects.}, journal = {Anais da Academia Brasileira de Ciencias}, volume = {90}, number = {1}, pages = {385-400}, doi = {10.1590/0001-3765201820160252}, pmid = {29424391}, issn = {1678-2690}, mesh = {Abscisic Acid/pharmacology ; Carica/anatomy & histology/drug effects/*embryology/*physiology ; Culture Media ; Germination/drug effects/physiology ; Indoleacetic Acids/*analysis ; Microscopy, Electron, Scanning ; Plant Growth Regulators/pharmacology ; Plant Leaves/drug effects/physiology ; Plant Shoots/drug effects/*physiology ; Plant Somatic Embryogenesis Techniques/*methods ; Reference Values ; Reproducibility of Results ; Time Factors ; }, abstract = {The aim of this study was to evaluate somatic embryogenesis in juvenile explants of the THB papaya cultivar. Apical shoots and cotyledonary leaves were inoculated in an induction medium composed of different concentrations of 2,4-D (6, 9, 12, 15 and 18 µM) or 4-CPA (19, 22, 25, 28 and 31 µM). The embryogenic calluses were transferred to a maturation medium for 30 days. Histological analysis were done during the induction and scanning electron microscopy after maturing. For both types of auxin, embryogenesis was achieved at higher frequencies with cotyledonary leaves incubated in induction medium than with apical shoots; except for callogenesis. The early-stage embryos (e.g., globular or heart-shape) predominated. Among the auxins, best results were observed in cotyledonary leaves induced with 4-CPA (25 µM). Histological analyses of the cotyledonary leaf-derived calluses confirmed that the somatic embryos (SEs) formed from parenchyma cells, predominantly differentiated via indirect and multicellular origin and infrequently via synchronized embryogenesis. The secondary embryogenesis was observed during induction and maturation phases in papaya THB cultivar. The combination of ABA (0.5 µM) and AC (15 g L-1) in maturation medium resulted in the highest somatic embryogenesis induction frequency (70 SEs callus-1) and the lowest percentage of early germination (4%).}, } @article {pmid29422410, year = {2018}, author = {Potjewyd, G and Moxon, S and Wang, T and Domingos, M and Hooper, NM}, title = {Tissue Engineering 3D Neurovascular Units: A Biomaterials and Bioprinting Perspective.}, journal = {Trends in biotechnology}, volume = {36}, number = {4}, pages = {457-472}, doi = {10.1016/j.tibtech.2018.01.003}, pmid = {29422410}, issn = {1879-3096}, support = {MR/L023784/1/MRC_/Medical Research Council/United Kingdom ; NC/K001744/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; PG/12/31/29527/BHF_/British Heart Foundation/United Kingdom ; MR/L023784/2/MRC_/Medical Research Council/United Kingdom ; MC_PC_16033/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Biocompatible Materials/*chemistry ; *Bioprinting ; Brain Diseases/therapy ; Extracellular Matrix/chemistry ; Humans ; Hydrogels/chemistry ; Models, Animal ; Neuroglia/chemistry ; Neurons/chemistry ; *Printing, Three-Dimensional ; *Tissue Engineering ; }, abstract = {Neurovascular dysfunction is a central process in the pathogenesis of stroke and most neurodegenerative diseases, including Alzheimer's disease. The multicellular neurovascular unit (NVU) combines the neural, vascular and extracellular matrix (ECM) components in an important interface whose correct functioning is critical to maintain brain health. Tissue engineering is now offering new tools and insights to advance our understanding of NVU function. Here, we review how the use of novel biomaterials to mimic the mechanical and functional cues of the ECM, coupled with precisely layered deposition of the different cells of the NVU through 3D bioprinting, is revolutionising the study of neurovascular function and dysfunction.}, } @article {pmid29415511, year = {2018}, author = {Henderson, SW and Wege, S and Gilliham, M}, title = {Plant Cation-Chloride Cotransporters (CCC): Evolutionary Origins and Functional Insights.}, journal = {International journal of molecular sciences}, volume = {19}, number = {2}, pages = {}, pmid = {29415511}, issn = {1422-0067}, mesh = {Biological Evolution ; Gene Expression ; Homeostasis ; Ions/metabolism ; Phenotype ; Plant Development/genetics ; Plant Proteins/genetics/*metabolism ; Plants/classification/drug effects/genetics/*metabolism ; Sodium-Potassium-Chloride Symporters/genetics/*metabolism ; Water/metabolism ; }, abstract = {Genomes of unicellular and multicellular green algae, mosses, grasses and dicots harbor genes encoding cation-chloride cotransporters (CCC). CCC proteins from the plant kingdom have been comparatively less well investigated than their animal counterparts, but proteins from both plants and animals have been shown to mediate ion fluxes, and are involved in regulation of osmotic processes. In this review, we show that CCC proteins from plants form two distinct phylogenetic clades (CCC1 and CCC2). Some lycophytes and bryophytes possess members from each clade, most land plants only have members of the CCC1 clade, and green algae possess only the CCC2 clade. It is currently unknown whether CCC1 and CCC2 proteins have similar or distinct functions, however they are both more closely related to animal KCC proteins compared to NKCCs. Existing heterologous expression systems that have been used to functionally characterize plant CCC proteins, namely yeast and Xenopus laevis oocytes, have limitations that are discussed. Studies from plants exposed to chemical inhibitors of animal CCC protein function are reviewed for their potential to discern CCC function in planta. Thus far, mutations in plant CCC genes have been evaluated only in two species of angiosperms, and such mutations cause a diverse array of phenotypes-seemingly more than could simply be explained by localized disruption of ion transport alone. We evaluate the putative roles of plant CCC proteins and suggest areas for future investigation.}, } @article {pmid29413517, year = {2018}, author = {Gavish, M and Veenman, L}, title = {Regulation of Mitochondrial, Cellular, and Organismal Functions by TSPO.}, journal = {Advances in pharmacology (San Diego, Calif.)}, volume = {82}, number = {}, pages = {103-136}, doi = {10.1016/bs.apha.2017.09.004}, pmid = {29413517}, issn = {1557-8925}, mesh = {Animals ; Evolution, Molecular ; Genes, Essential ; Homeostasis ; Humans ; Mitochondria/*metabolism ; Reactive Oxygen Species/metabolism ; Receptors, GABA/*metabolism ; }, abstract = {In 1999, the enigma of the 18kDa mitochondrial translocator protein (TSPO), also known as the peripheral-type benzodiazepine receptor, was the seeming disparity of the many functions attributed to TSPO, ranging from the potential of TSPO acting as a housekeeping gene at molecular biological levels to adaptations to stress, and even involvement in higher emotional and cognitive functioning, such as anxiety and depression. In the years since then, knowledge regarding the many functions modulated by TSPO has expanded, and understanding has deepened. In addition, new functions could be firmly associated with TSPO, such as regulation of programmed cell death and modulation of gene expression. Interestingly, control by the mitochondrial TSPO over both of these life and death functions appears to include Ca[++] homeostasis, generation of reactive oxygen species (ROS), and ATP production. Other mitochondrial functions under TSPO control are considered to be steroidogenesis and tetrapyrrole metabolism. As TSPO effects on gene expression and on programmed cell death can be related to the wide range of functions that can be associated with TSPO, several of these five elements of Ca[++], ROS, ATP, steroids, and tetrapyrroles may indeed form the basis of TSPO's capability to operate as a multifunctional housekeeping gene to maintain homeostasis of the cell and of the whole multicellular organism.}, } @article {pmid29411901, year = {2018}, author = {Taverne, YJ and Merkus, D and Bogers, AJ and Halliwell, B and Duncker, DJ and Lyons, TW}, title = {Reactive Oxygen Species: Radical Factors in the Evolution of Animal Life: A molecular timescale from Earth's earliest history to the rise of complex life.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {40}, number = {3}, pages = {}, doi = {10.1002/bies.201700158}, pmid = {29411901}, issn = {1521-1878}, mesh = {Animals ; Atmosphere/analysis ; Bacteria/chemistry/metabolism ; *Biological Evolution ; Earth, Planet ; Electron Transport ; Energy Metabolism ; *Origin of Life ; Oxidation-Reduction ; Oxygen/chemistry/*metabolism ; Photosynthesis/*physiology ; Plants/chemistry/*metabolism ; Reactive Oxygen Species/chemistry/*metabolism ; Time Factors ; }, abstract = {Introduction of O2 to Earth's early biosphere stimulated remarkable evolutionary adaptations, and a wide range of electron acceptors allowed diverse, energy-yielding metabolic pathways. Enzymatic reduction of O2 yielded a several-fold increase in energy production, enabling evolution of multi-cellular animal life. However, utilization of O2 also presented major challenges as O2 and many of its derived reactive oxygen species (ROS) are highly toxic, possibly impeding multicellular evolution after the Great Oxidation Event. Remarkably, ROS, and especially hydrogen peroxide, seem to play a major part in early diversification and further development of cellular respiration and other oxygenic pathways, thus becoming an intricate part of evolution of complex life. Hence, although harnessing of chemical and thermo-dynamic properties of O2 for aerobic metabolism is generally considered to be an evolutionary milestone, the ability to use ROS for cell signaling and regulation may have been the first true breakthrough in development of complex life.}, } @article {pmid29405978, year = {2018}, author = {Wechman, SL and Pradhan, AK and DeSalle, R and Das, SK and Emdad, L and Sarkar, D and Fisher, PB}, title = {New Insights Into Beclin-1: Evolution and Pan-Malignancy Inhibitor Activity.}, journal = {Advances in cancer research}, volume = {137}, number = {}, pages = {77-114}, pmid = {29405978}, issn = {2162-5557}, support = {K12 GM093857/GM/NIGMS NIH HHS/United States ; P30 CA016059/CA/NCI NIH HHS/United States ; R01 CA097318/CA/NCI NIH HHS/United States ; R01 CA168517/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*therapeutic use ; Beclin-1/*metabolism ; *Evolution, Molecular ; Genes, Tumor Suppressor ; Humans ; *Molecular Targeted Therapy ; Neoplasms/*drug therapy/*metabolism/pathology ; }, abstract = {Autophagy is a functionally conserved self-degradation process that facilitates the survival of eukaryotic life via the management of cellular bioenergetics and maintenance of the fidelity of genomic DNA. The first known autophagy inducer was Beclin-1. Beclin-1 is expressed in multicellular eukaryotes ranging throughout plants to animals, comprising a nonmonophyllic group, as shown in this report via aggressive BLAST searches. In humans, Beclin-1 is a haploinsuffient tumor suppressor as biallelic deletions have not been observed in patient tumors clinically. Therefore, Beclin-1 fails the Knudson hypothesis, implicating expression of at least one Beclin-1 allele is essential for cancer cell survival. However, Beclin-1 is frequently monoallelically deleted in advanced human cancers and the expression of two Beclin-1 allelles is associated with greater anticancer effects. Overall, experimental evidence suggests that Beclin-1 inhibits tumor formation, angiogenesis, and metastasis alone and in cooperation with the tumor suppressive molecules UVRAG, Bif-1, Ambra1, and MDA-7/IL-24 via diverse mechanisms of action. Conversely, Beclin-1 is upregulated in cancer stem cells (CSCs), portending a role in cancer recurrence, and highlighting this molecule as an intriguing molecular target for the treatment of CSCs. Many aspects of Beclin-1's biological effects remain to be studied. The consequences of these BLAST searches on the molecular evolution of Beclin-1, and the eukaryotic branches of the tree of life, are discussed here in greater detail with future inquiry focused upon protist taxa. Also in this review, the effects of Beclin-1 on tumor suppression and cancer malignancy are discussed. Beclin-1 holds significant promise for the development of novel targeted cancer therapeutics and is anticipated to lead to a many advances in our understanding of eukaryotic evolution, multicellularity, and even the treatment of CSCs in the coming decades.}, } @article {pmid29400699, year = {2018}, author = {Ćetković, H and Bosnar, MH and Perina, D and Mikoč, A and Deželjin, M and Belužić, R and Bilandžija, H and Ruiz-Trillo, I and Harcet, M}, title = {Characterization of a group I Nme protein of Capsaspora owczarzaki-a close unicellular relative of animals.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {98}, number = {3}, pages = {304-314}, pmid = {29400699}, issn = {1530-0307}, mesh = {Amino Acid Sequence ; Cell Migration Assays ; *Cell Movement ; Eukaryota/*enzymology/genetics ; Evolution, Molecular ; HeLa Cells ; Humans ; NM23 Nucleoside Diphosphate Kinases/chemistry/genetics/*metabolism ; }, abstract = {Nucleoside diphosphate kinases are enzymes present in all domains of life. In animals, they are called Nme or Nm23 proteins, and are divided into group I and II. Human Nme1 was the first protein identified as a metastasis suppressor. Because of its medical importance, it has been extensively studied. In spite of the large research effort, the exact mechanism of metastasis suppression remains unclear. It is unknown which of the biochemical properties or biological functions are responsible for the antimetastatic role of the mammalian Nme1. Furthermore, it is not clear at which point in the evolution of life group I Nme proteins acquired the potential to suppress metastasis, a process that is usually associated with complex animals. In this study we performed a series of tests and assays on a group I Nme protein from filasterean Capsaspora owczarzaki, a close unicellular relative of animals. The aim was to compare the protein to the well-known human Nme1 and Nme2 homologs, as well as with the homolog from a simple animal-sponge (Porifera), in order to see how the proteins changed with the transition to multicellularity, and subsequently in the evolution of complex animals. We found that premetazoan-type protein is highly similar to the homologs from sponge and human, in terms of biochemical characteristics and potential biological functions. Like the human Nme1 and Nme2, it is able to diminish the migratory potential of human cancer cells in culture.}, } @article {pmid29398221, year = {2018}, author = {Pang, K and Tang, Q and Chen, L and Wan, B and Niu, C and Yuan, X and Xiao, S}, title = {Nitrogen-Fixing Heterocystous Cyanobacteria in the Tonian Period.}, journal = {Current biology : CB}, volume = {28}, number = {4}, pages = {616-622.e1}, doi = {10.1016/j.cub.2018.01.008}, pmid = {29398221}, issn = {1879-0445}, mesh = {China ; Cyanobacteria/*classification/cytology/physiology ; *Fossils ; *Nitrogen Fixation ; }, abstract = {Cyanobacteria were the ultimate ancestor of all plastids and, for much of Earth's history, the only source of biogenic oxygen and a major source of fixed carbon and nitrogen. One cyanobacterial clade, subsections IV+V, is characterized by multicellularity and cell differentiation, with many members bearing specialized nitrogen-fixing (or diazotrophic) heterocysts and encysting akinetes [1-3]. Molecular clock estimates of the divergence time of this clade are highly variable, ranging from ∼2,000 Ma (mega-annum) [4-9] to ∼500 Ma [10]. The older estimates are invariably calibrated by putative akinete fossils from Paleoproterozoic-Mesoproterozoic rocks around 2,100-1,400 Ma [3, 11, 12]. However, the interpretation of these fossils as akinetes has been questioned [13], and the next oldest akinete and heterocyst fossils are ∼410 Ma [14]. Thus, the scarcity of reliable heterocystous cyanobacterial fossils significantly hampers our understanding of the evolution of complex multicellularity among cyanobacteria, their role in regulating geochemical cycles in the geological past, and our ability to calibrate cyanobacterial molecular clocks. Here, we report Tonian (∼1,000-720 Ma) filamentous cyanobacteria that are characterized by large cells, binary fission (for filament elongation), hormogonia (for asexual reproduction and dispersal), probable akinetes (for survival in adverse conditions), and by implication, diazotrophic heterocysts. The new fossils provide a minimum age calibration on the divergence of subsections IV+V and place a firm constraint on the evolution of akinetes and heterocysts.}, } @article {pmid29395928, year = {2018}, author = {Yamaoka, S and Nishihama, R and Yoshitake, Y and Ishida, S and Inoue, K and Saito, M and Okahashi, K and Bao, H and Nishida, H and Yamaguchi, K and Shigenobu, S and Ishizaki, K and Yamato, KT and Kohchi, T}, title = {Generative Cell Specification Requires Transcription Factors Evolutionarily Conserved in Land Plants.}, journal = {Current biology : CB}, volume = {28}, number = {3}, pages = {479-486.e5}, doi = {10.1016/j.cub.2017.12.053}, pmid = {29395928}, issn = {1879-0445}, mesh = {Basic Helix-Loop-Helix Transcription Factors/*genetics/metabolism ; *Cell Differentiation ; *Evolution, Molecular ; Germ Cells, Plant/*growth & development/metabolism ; Marchantia/genetics/*physiology ; Phylogeny ; Plant Proteins/*genetics/metabolism ; }, abstract = {Land plants differentiate germ cells in the haploid gametophyte. In flowering plants, a generative cell is specified as a precursor that subsequently divides into two sperm cells in the developing male gametophyte, pollen. Generative cell specification requires cell-cycle control and microtubule-dependent nuclear relocation (reviewed in [1-3]). However, the generative cell fate determinant and its evolutionary origin are still unknown. In bryophytes, gametophytes produce eggs and sperm in multicellular reproductive organs called archegonia and antheridia, respectively, or collectively called gametangia. Given the monophyletic origin of land plants [4-6], evolutionarily conserved mechanisms may play key roles in these diverse reproductive processes. Here, we showed that a single member of the subfamily VIIIa of basic helix-loop-helix (bHLH) transcription factors in the liverwort Marchantia polymorpha primarily accumulated in the initial cells and controlled their development into gametangia. We then demonstrated that an Arabidopsis thaliana VIIIa bHLH transiently accumulated in the smaller daughter cell after an asymmetric division of the meiosis-derived microspore and was required for generative cell specification redundantly with its paralog. Furthermore, these A. thaliana VIIIa bHLHs were functionally replaceable by the M. polymorpha VIIIa bHLH. These findings suggest the VIIIa bHLH proteins as core regulators for reproductive development, including germ cell differentiation, since an early stage of land plant evolution.}, } @article {pmid29394379, year = {2018}, author = {Niklas, KJ and Dunker, AK and Yruela, I}, title = {The evolutionary origins of cell type diversification and the role of intrinsically disordered proteins.}, journal = {Journal of experimental botany}, volume = {69}, number = {7}, pages = {1437-1446}, doi = {10.1093/jxb/erx493}, pmid = {29394379}, issn = {1460-2431}, mesh = {*Alternative Splicing ; Cell Proliferation ; Eukaryotic Cells/*cytology/metabolism ; *Evolution, Molecular ; Gene Regulatory Networks/*physiology ; Genes, Plant ; Intrinsically Disordered Proteins/genetics/*metabolism ; Plant Proteins/genetics/*metabolism ; *Protein Processing, Post-Translational ; RNA, Messenger/genetics/metabolism ; }, abstract = {The evolution of complex multicellular life forms occurred multiple times and was attended by cell type specialization. We review seven lines of evidence indicating that intrinsically disordered/ductile proteins (IDPs) played a significant role in the evolution of multicellularity and cell type specification: (i) most eukaryotic transcription factors (TFs) and multifunctional enzymes contain disproportionately long IDP sequences (≥30 residues in length), whereas highly conserved enzymes are normally IDP region poor; (ii) ~80% of the proteome involved in development are IDPs; (iii) the majority of proteins undergoing alternative splicing (AS) of pre-mRNA contain significant IDP regions; (iv) proteins encoded by DNA regions flanking crossing-over 'hot spots' are significantly enriched in IDP regions; (v) IDP regions are disproportionately subject to combinatorial post-translational modifications (PTMs) as well as AS; (vi) proteins involved in transcription and RNA processing are enriched in IDP regions; and (vii) a strong positive correlation exists between the number of different cell types and the IDP proteome fraction across a broad spectrum of uni- and multicellular algae, plants, and animals. We argue that the multifunctionalities conferred by IDPs and the disproportionate involvement of IDPs with AS and PTMs provided a IDP-AS-PTM 'motif' that significantly contributed to the evolution of multicellularity in all major eukaryotic lineages.}, } @article {pmid29385672, year = {2018}, author = {Park, B and Shin, DY and Jeon, TJ}, title = {CBP7 Interferes with the Multicellular Development of Dictyostelium Cells by Inhibiting Chemoattractant-Mediated Cell Aggregation.}, journal = {Molecules and cells}, volume = {41}, number = {2}, pages = {103-109}, pmid = {29385672}, issn = {0219-1032}, mesh = {Calcium/metabolism ; Calcium-Binding Proteins/classification/genetics/*metabolism ; Chemotactic Factors/genetics/metabolism ; *Chemotaxis ; Cyclic AMP/metabolism ; Dictyostelium/cytology/genetics/*metabolism ; Movement ; Phylogeny ; *Signal Transduction ; }, abstract = {Calcium ions are involved in the regulation of diverse cellular processes. Fourteen genes encoding calcium binding proteins have been identified in Dictyostelium. CBP7, one of the 14 CBPs, is composed of 169 amino acids and contains four EF-hand motifs. Here, we investigated the roles of CBP7 in the development and cell migration of Dictyostelium cells and found that high levels of CBP7 exerted a negative effect on cells aggregation during development, possibly by inhibiting chemoattractant-directed cell migration. While cells lacking CBP7 exhibited normal development and chemotaxis similar that of wild-type cells, CBP7 overexpressing cells completely lost their chemotactic abilities to move toward increasing cAMP concentrations. This resulted in inhibition of cellular aggregation, a process required for forming multicellular organisms during development. Low levels of cytosolic free calcium were observed in CBP7 overexpressing cells, which was likely the underlying cause of their lack of chemotaxis. Our results demonstrate that CBP7 plays an important role in cell spreading and cell-substrate adhesion. cbp7 null cells showed decreased cell size and cell-substrate adhesion. The present study contributes to further understanding the role of calcium signaling in regulation of cell migration and development.}, } @article {pmid31162574, year = {2018}, author = {McGrath, C}, title = {Highlight: Origins of Multicellularity Revealed by Single-Celled Amoebae.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {705-706}, pmid = {31162574}, issn = {1759-6653}, mesh = {*Amoeba ; Biological Evolution ; Phylogeny ; }, } @article {pmid29381766, year = {2018}, author = {Boyd, M and Rosenzweig, F and Herron, MD}, title = {Analysis of motility in multicellular Chlamydomonas reinhardtii evolved under predation.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0192184}, pmid = {29381766}, issn = {1932-6203}, mesh = {Animals ; *Biological Evolution ; Chlamydomonas reinhardtii/*physiology ; *Predatory Behavior ; }, abstract = {The advent of multicellularity was a watershed event in the history of life, yet the transition from unicellularity to multicellularity is not well understood. Multicellularity opens up opportunities for innovations in intercellular communication, cooperation, and specialization, which can provide selective advantages under certain ecological conditions. The unicellular alga Chlamydomonas reinhardtii has never had a multicellular ancestor yet it is closely related to the volvocine algae, a clade containing taxa that range from simple unicells to large, specialized multicellular colonies. Simple multicellular structures have been observed to evolve in C. reinhardtii in response to predation or to settling rate-based selection. Structures formed in response to predation consist of individual cells confined within a shared transparent extracellular matrix. Evolved isolates form such structures obligately under culture conditions in which their wild type ancestors do not, indicating that newly-evolved multicellularity is heritable. C. reinhardtii is capable of photosynthesis, and possesses an eyespot and two flagella with which it moves towards or away from light in order to optimize input of radiant energy. Motility contributes to C. reinhardtii fitness because it allows cells or colonies to achieve this optimum. Utilizing phototaxis to assay motility, we determined that newly evolved multicellular strains do not exhibit significant directional movement, even though the flagellae of their constituent unicells are present and active. In C. reinhardtii the first steps towards multicellularity in response to predation appear to result in a trade-off between motility and differential survivorship, a trade-off that must be overcome by further genetic change to ensure long-term success of the new multicellular organism.}, } @article {pmid29381236, year = {2018}, author = {Li, Y and Zuo, S and Zhang, Z and Li, Z and Han, J and Chu, Z and Hasterok, R and Wang, K}, title = {Centromeric DNA characterization in the model grass Brachypodium distachyon provides insights on the evolution of the genus.}, journal = {The Plant journal : for cell and molecular biology}, volume = {93}, number = {6}, pages = {1088-1101}, doi = {10.1111/tpj.13832}, pmid = {29381236}, issn = {1365-313X}, mesh = {Amino Acid Sequence ; Brachypodium/classification/*genetics/metabolism ; Centromere/*genetics/metabolism ; Chromosomes, Plant/genetics/metabolism ; DNA, Plant/*genetics/metabolism ; Evolution, Molecular ; Genome, Plant/*genetics ; Histones/genetics/metabolism ; In Situ Hybridization, Fluorescence ; Nucleosomes/genetics/metabolism ; Phylogeny ; Plant Proteins/genetics/metabolism ; Polyploidy ; Protein Binding ; Sequence Homology, Amino Acid ; }, abstract = {Brachypodium distachyon is a well-established model monocot plant, and its small and compact genome has been used as an accurate reference for the much larger and often polyploid genomes of cereals such as Avena sativa (oats), Hordeum vulgare (barley) and Triticum aestivum (wheat). Centromeres are indispensable functional units of chromosomes and they play a core role in genome polyploidization events during evolution. As the Brachypodium genus contains about 20 species that differ significantly in terms of their basic chromosome numbers, genome size, ploidy levels and life strategies, studying their centromeres may provide important insight into the structure and evolution of the genome in this interesting and important genus. In this study, we isolated the centromeric DNA of the B. distachyon reference line Bd21 and characterized its composition via the chromatin immunoprecipitation of the nucleosomes that contain the centromere-specific histone CENH3. We revealed that the centromeres of Bd21 have the features of typical multicellular eukaryotic centromeres. Strikingly, these centromeres contain relatively few centromeric satellite DNAs; in particular, the centromere of chromosome 5 (Bd5) consists of only ~40 kb. Moreover, the centromeric retrotransposons in B. distachyon (CRBds) are evolutionarily young. These transposable elements are located both within and adjacent to the CENH3 binding domains, and have similar compositions. Moreover, based on the presence of CRBds in the centromeres, the species in this study can be grouped into two distinct lineages. This may provide new evidence regarding the phylogenetic relationships within the Brachypodium genus.}, } @article {pmid29378020, year = {2018}, author = {Hillmann, F and Forbes, G and Novohradská, S and Ferling, I and Riege, K and Groth, M and Westermann, M and Marz, M and Spaller, T and Winckler, T and Schaap, P and Glöckner, G}, title = {Multiple Roots of Fruiting Body Formation in Amoebozoa.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {591-606}, pmid = {29378020}, issn = {1759-6653}, mesh = {Amoebozoa/cytology/*genetics/*growth & development ; Cell Communication ; Dictyostelium/cytology/genetics/growth & development ; Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Phylogeny ; Protozoan Proteins/genetics ; Transcriptome ; }, abstract = {Establishment of multicellularity represents a major transition in eukaryote evolution. A subgroup of Amoebozoa, the dictyosteliids, has evolved a relatively simple aggregative multicellular stage resulting in a fruiting body supported by a stalk. Protosteloid amoeba, which are scattered throughout the amoebozoan tree, differ by producing only one or few single stalked spores. Thus, one obvious difference in the developmental cycle of protosteliids and dictyosteliids seems to be the establishment of multicellularity. To separate spore development from multicellular interactions, we compared the genome and transcriptome of a Protostelium species (Protostelium aurantium var. fungivorum) with those of social and solitary members of the Amoebozoa. During fruiting body formation nearly 4,000 genes, corresponding to specific pathways required for differentiation processes, are upregulated. A comparison with genes involved in the development of dictyosteliids revealed conservation of >500 genes, but most of them are also present in Acanthamoeba castellanii for which fruiting bodies have not been documented. Moreover, expression regulation of those genes differs between P. aurantium and Dictyostelium discoideum. Within Amoebozoa differentiation to fruiting bodies is common, but our current genome analysis suggests that protosteliids and dictyosteliids used different routes to achieve this. Most remarkable is both the large repertoire and diversity between species in genes that mediate environmental sensing and signal processing. This likely reflects an immense adaptability of the single cell stage to varying environmental conditions. We surmise that this signaling repertoire provided sufficient building blocks to accommodate the relatively simple demands for cell-cell communication in the early multicellular forms.}, } @article {pmid29375513, year = {2017}, author = {Yin, QJ and Zhang, WJ and Qi, XQ and Zhang, SD and Jiang, T and Li, XG and Chen, Y and Santini, CL and Zhou, H and Chou, IM and Wu, LF}, title = {High Hydrostatic Pressure Inducible Trimethylamine N-Oxide Reductase Improves the Pressure Tolerance of Piezosensitive Bacteria Vibrio fluvialis.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {2646}, pmid = {29375513}, issn = {1664-302X}, abstract = {High hydrostatic pressure (HHP) exerts severe effects on cellular processes including impaired cell division, abolished motility and affected enzymatic activities. Transcriptomic and proteomic analyses showed that bacteria switch the expression of genes involved in multiple energy metabolism pathways to cope with HHP. We sought evidence of a changing bacterial metabolism by supplying appropriate substrates that might have beneficial effects on the bacterial lifestyle at elevated pressure. We isolated a piezosensitive marine bacterium Vibrio fluvialis strain QY27 from the South China Sea. When trimethylamine N-oxide (TMAO) was used as an electron acceptor for energy metabolism, QY27 exhibited a piezophilic-like phenotype with an optimal growth at 30 MPa. Raman spectrometry and biochemistry analyses revealed that both the efficiency of the TMAO metabolism and the activity of the TMAO reductase increased under high pressure conditions. Among the two genes coding for TMAO reductase catalytic subunits, the expression level and enzymatic activity of TorA was up-regulated by elevated pressure. Furthermore, a genetic interference assay with the CRISPR-dCas9 system demonstrated that TorA is essential for underpinning the improved pressure tolerance of QY27. We extended the study to Vibrio fluvialis type strain ATCC33809 and observed the same phenotype of TMAO-metabolism improved the pressure tolerance. These results provide compelling evidence for the determinant role of metabolism in the adaption of bacteria to the deep-sea ecosystems with HHP.}, } @article {pmid29373067, year = {2017}, author = {Lindström, JB and Pierce, NT and Latz, MI}, title = {Role of TRP Channels in Dinoflagellate Mechanotransduction.}, journal = {The Biological bulletin}, volume = {233}, number = {2}, pages = {151-167}, doi = {10.1086/695421}, pmid = {29373067}, issn = {1939-8697}, mesh = {Biological Evolution ; Dinoflagellida/classification/genetics/*physiology ; Signal Transduction/genetics ; Transient Receptor Potential Channels/genetics/*metabolism ; }, abstract = {Transient receptor potential (TRP) ion channels are common components of mechanosensing pathways, mainly described in mammals and other multicellular organisms. To gain insight into the evolutionary origins of eukaryotic mechanosensory proteins, we investigated the involvement of TRP channels in mechanosensing in a unicellular eukaryotic protist, the dinoflagellate Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from the L. polyedra transcriptome revealed six sequences with high similarity to human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were identified in all sequences. In a phylogenetic tree including all mammalian TRP subfamilies and TRP channel sequences from unicellular and multicellular organisms, the L. polyedra sequences grouped with the TRPM, TPPML, and TRPP clades. In pharmacological experiments, we used the intrinsic bioluminescence of L. polyedra as a reporter of mechanoresponsivity. Capsaicin and RN1734, agonists of mammalian TRPV, and arachidonic acid, an agonist of mammalian TRPV, TRPA, TRPM, and Drosophila TRP, all stimulated bioluminescence in L. polyedra. Mechanical stimulation of bioluminescence, but not capsaicin-stimulated bioluminescence, was inhibited by gadolinium (Gd[3+]), a general inhibitor of mechanosensitive ion channels, and the phospholipase C (PLC) inhibitor U73122. These pharmacological results are consistent with the involvement of TRP-like channels in mechanosensing by L. polyedra. The TRP channels do not appear to be mechanoreceptors but rather are components of the mechanotransduction signaling pathway and may be activated via a PLC-dependent mechanism. The presence and function of TRP channels in a dinoflagellate emphasize the evolutionary conservation of both the channel structures and their functions.}, } @article {pmid29361519, year = {2018}, author = {Cocorocchio, M and Baldwin, AJ and Stewart, B and Kim, L and Harwood, AJ and Thompson, CRL and Andrews, PLR and Williams, RSB}, title = {Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues in Dictyostelium discoideum.}, journal = {Disease models & mechanisms}, volume = {11}, number = {1}, pages = {}, pmid = {29361519}, issn = {1754-8411}, support = {BB/M007146/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; NC/M001504/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; 101582Z/13/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Antioxidants/pharmacology ; Curcumin/analogs & derivatives/chemistry/*pharmacology ; Dictyostelium/drug effects/growth & development/*metabolism ; Ligands ; Molecular Docking Simulation ; Presenilin-1/*metabolism ; Protein Phosphatase 2/*metabolism ; *Sequence Homology, Amino Acid ; }, abstract = {Natural compounds often have complex molecular structures and unknown molecular targets. These characteristics make them difficult to analyse using a classical pharmacological approach. Curcumin, the main curcuminoid of turmeric, is a complex molecule possessing wide-ranging biological activities, cellular mechanisms and roles in potential therapeutic treatment, including Alzheimer's disease and cancer. Here, we investigate the physiological effects and molecular targets of curcumin in Dictyostelium discoideum We show that curcumin exerts acute effects on cell behaviour, reduces cell growth and slows multicellular development. We employed a range of structurally related compounds to show the distinct role of different structural groups in curcumin's effects on cell behaviour, growth and development, highlighting active moieties in cell function, and showing that these cellular effects are unrelated to the well-known antioxidant activity of curcumin. Molecular mechanisms underlying the effect of curcumin and one synthetic analogue (EF24) were then investigated to identify a curcumin-resistant mutant lacking the protein phosphatase 2A regulatory subunit (PsrA) and an EF24-resistant mutant lacking the presenilin 1 orthologue (PsenB). Using in silico docking analysis, we then showed that curcumin might function through direct binding to a key regulatory region of PsrA. These findings reveal novel cellular and molecular mechanisms for the function of curcumin and related compounds.}, } @article {pmid29348641, year = {2018}, author = {Hammarlund, EU and von Stedingk, K and Påhlman, S}, title = {Refined control of cell stemness allowed animal evolution in the oxic realm.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {220-228}, doi = {10.1038/s41559-017-0410-5}, pmid = {29348641}, issn = {2397-334X}, mesh = {Anaerobiosis ; Animals ; *Biological Evolution ; Cell Hypoxia/*physiology ; Oxygen/*physiology ; Stem Cells/*physiology ; }, abstract = {Animal diversification on Earth has long been presumed to be associated with the increasing extent of oxic niches. Here, we challenge that view. We start with the fact that hypoxia (<1-3% O2) maintains cellular immaturity (stemness), whereas adult stem cells continuously-and paradoxically-regenerate animal tissue in oxygenated settings. Novel insights from tumour biology illuminate how cell stemness nevertheless can be achieved through the action of oxygen-sensing transcription factors in oxygenated, regenerating tissue. We suggest that these hypoxia-inducible transcription factors provided animals with unprecedented control over cell stemness that allowed them to cope with fluctuating oxygen concentrations. Thus, a refinement of the cellular hypoxia-response machinery enabled cell stemness at oxic conditions and, then, animals to evolve into the oxic realm. This view on the onset of animal diversification is consistent with geological evidence and provides a new perspective on the challenges and evolution of multicellular life.}, } @article {pmid29348455, year = {2018}, author = {Libby, E and Driscoll, WW and Ratcliff, WC}, title = {Programmed cell death can increase the efficacy of microbial bet -hedging.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {1120}, pmid = {29348455}, issn = {2045-2322}, abstract = {Programmed cell death (PCD) occurs in both unicellular and multicellular organisms. While PCD plays a key role in the development and maintenance of multicellular organisms, explaining why single-celled organisms would evolve to actively commit suicide has been far more challenging. Here, we explore the potential for PCD to act as an accessory to microbial bet-hedging strategies that utilize stochastic phenotype switching. We consider organisms that face unpredictable and recurring disasters, in which fitness depends on effective phenotypic diversification. We show that when reproductive opportunities are limited by carrying capacity, PCD drives population turnover, providing increased opportunities for phenotypic diversification through stochastic phenotype switching. The main cost of PCD, providing resources for growth to a PCD(-) competitor, is ameliorated by genetic assortment in spatially structured populations. Using agent -based simulations, we explore how basic demographic factors, namely bottlenecks and local dispersal, can generate sufficient spatial structure to favor the evolution of high PCD rates.}, } @article {pmid29340409, year = {2018}, author = {Ray, A and Morford, RK and Ghaderi, N and Odde, DJ and Provenzano, PP}, title = {Dynamics of 3D carcinoma cell invasion into aligned collagen.}, journal = {Integrative biology : quantitative biosciences from nano to macro}, volume = {10}, number = {2}, pages = {100-112}, pmid = {29340409}, issn = {1757-9708}, support = {R01 CA172986/CA/NCI NIH HHS/United States ; R01 CA181385/CA/NCI NIH HHS/United States ; U54 CA210190/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/metabolism/pathology ; Carcinoma/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/physiology ; Collagen/metabolism ; Extracellular Matrix/metabolism/pathology ; Female ; Humans ; Imaging, Three-Dimensional ; Microscopy, Fluorescence, Multiphoton ; Models, Biological ; Neoplasm Invasiveness/*pathology/physiopathology ; Systems Biology ; }, abstract = {Carcinoma cells frequently expand and invade from a confined lesion, or multicellular clusters, into and through the stroma on the path to metastasis, often with an efficiency dictated by the architecture and composition of the microenvironment. Specifically, in desmoplastic carcinomas such as those of the breast, aligned collagen tracks provide contact guidance cues for directed cancer cell invasion. Yet, the evolving dynamics of this process of invasion remains poorly understood, in part due to difficulties in continuously capturing both spatial and temporal heterogeneity and progression to invasion in experimental systems. Therefore, to study the local invasion process from cell dense clusters into aligned collagen architectures found in solid tumors, we developed a novel engineered 3D invasion platform that integrates an aligned collagen matrix with a cell dense tumor-like plug. Using multiphoton microscopy and quantitative analysis of cell motility, we track the invasion of cancer cells from cell-dense bulk clusters into the pre-aligned 3D matrix, and define the temporal evolution of the advancing invasion fronts over several days. This enables us to identify and probe cell dynamics in key regions of interest: behind, at, and beyond the edge of the invading lesion at distinct time points. Analysis of single cell migration identifies significant spatial heterogeneity in migration behavior between cells in the highly cell-dense region behind the leading edge of the invasion front and cells at and beyond the leading edge. Moreover, temporal variations in motility and directionality are also observed between cells within the cell-dense tumor-like plug and the leading invasive edge as its boundary extends into the anisotropic collagen over time. Furthermore, experimental results combined with mathematical modeling demonstrate that in addition to contact guidance, physical crowding of cells is a key regulating factor orchestrating variability in single cell migration during invasion into anisotropic ECM. Thus, our novel platform enables us to capture spatio-temporal dynamics of cell behavior behind, at, and beyond the invasive front and reveals heterogeneous, local interactions that lead to the emergence and maintenance of the advancing front.}, } @article {pmid29337961, year = {2018}, author = {Trigos, AS and Pearson, RB and Papenfuss, AT and Goode, DL}, title = {How the evolution of multicellularity set the stage for cancer.}, journal = {British journal of cancer}, volume = {118}, number = {2}, pages = {145-152}, pmid = {29337961}, issn = {1532-1827}, mesh = {Animals ; Biological Evolution ; Gene Regulatory Networks ; Humans ; Neoplasms/*genetics/*pathology ; }, abstract = {Neoplastic growth and many of the hallmark properties of cancer are driven by the disruption of molecular networks established during the emergence of multicellularity. Regulatory pathways and molecules that evolved to impose regulatory constraints upon networks established in earlier unicellular organisms enabled greater communication and coordination between the diverse cell types required for multicellularity, but also created liabilities in the form of points of vulnerability in the network that when mutated or dysregulated facilitate the development of cancer. These factors are usually overlooked in genomic analyses of cancer, but understanding where vulnerabilities to cancer lie in the networks of multicellular species would provide important new insights into how core molecular processes and gene regulation change during tumourigenesis. We describe how the evolutionary origins of genes influence their roles in cancer, and how connections formed between unicellular and multicellular genes that act as key regulatory hubs for normal tissue homeostasis can also contribute to malignant transformation when disrupted. Tumours in general are characterised by increased dependence on unicellular processes for survival, and major dysregulation of the control structures imposed on these processes during the evolution of multicellularity. Mounting molecular evidence suggests altered interactions at the interface between unicellular and multicellular genes play key roles in the initiation and progression of cancer. Furthermore, unicellular network regions activated in cancer show high degrees of robustness and plasticity, conferring increased adaptability to tumour cells by supporting effective responses to environmental pressures such as drug exposure. Examining how the links between multicellular and unicellular regions get disrupted in tumours has great potential to identify novel drivers of cancer, and to guide improvements to cancer treatment by identifying more effective therapeutic strategies. Recent successes in targeting unicellular processes by novel compounds underscore the logic of such approaches. Further gains could come from identifying genes at the interface between unicellular and multicellular processes and manipulating the communication between network regions of different evolutionary ages.}, } @article {pmid29326726, year = {2017}, author = {Zheng, Q and Ma, A and Yuan, L and Gao, N and Feng, Q and Franc, NC and Xiao, H}, title = {Apoptotic Cell Clearance in Drosophila melanogaster.}, journal = {Frontiers in immunology}, volume = {8}, number = {}, pages = {1881}, pmid = {29326726}, issn = {1664-3224}, abstract = {The swift clearance of apoptotic cells (ACs) (efferocytosis) by phagocytes is a critical event during development of all multicellular organisms. It is achieved through phagocytosis by professional or amateur phagocytes. Failure in this process can lead to the development of inflammatory autoimmune or neurodegenerative diseases. AC clearance has been conserved throughout evolution, although many details in its mechanisms remain to be explored. It has been studied in the context of mammalian macrophages, and in the nematode Caenorhabditis elegans, which lacks "professional" phagocytes such as macrophages, but in which other cell types can engulf apoptotic corpses. In Drosophila melanogaster, ACs are engulfed by macrophages, glial, and epithelial cells. Drosophila macrophages perform similar functions to those of mammalian macrophages. They are professional phagocytes that participate in phagocytosis of ACs and pathogens. Study of AC clearance in Drosophila has identified some key elements, like the receptors Croquemort and Draper, promoting Drosophila as a suitable model to genetically dissect this process. In this review, we survey recent works of AC clearance pathways in Drosophila, and discuss the physiological outcomes and consequences of this process.}, } @article {pmid29322818, year = {2018}, author = {Baig, AM and Zohaib, R and Tariq, S and Ahmad, HR}, title = {Evolution of pH buffers and water homeostasis in eukaryotes: homology between humans and Acanthamoeba proteins.}, journal = {Future microbiology}, volume = {13}, number = {}, pages = {195-207}, doi = {10.2217/fmb-2017-0116}, pmid = {29322818}, issn = {1746-0921}, mesh = {Acanthamoeba castellanii/*genetics/*physiology ; Amino Acid Sequence ; Carbonic Anhydrases/chemistry/genetics ; Computational Biology ; *Evolution, Molecular ; Homeostasis/*genetics ; Humans ; Hydrogen-Ion Concentration ; Membrane Transport Proteins/chemistry/genetics ; Models, Molecular ; Molecular Sequence Data ; Protozoan Proteins/chemistry/*genetics ; Sequence Homology, Amino Acid ; Water ; }, abstract = {AIM: This study intended to trace the evolution of acid-base buffers and water homeostasis in eukaryotes. Acanthamoeba castellanii was selected as a model unicellular eukaryote for this purpose. Homologies of proteins involved in pH and water regulatory mechanisms at cellular levels were compared between humans and A. castellanii.

MATERIALS & METHODS: Amino acid sequence homology, structural homology, 3D modeling and docking prediction were done to show the extent of similarities between carbonic anhydrase 1 (CA1), aquaporin (AQP), band-3 protein and H[+] pump. Experimental assays were done with acetazolamide (AZM), brinzolamide and mannitol to observe their effects on the trophozoites of  A. castellanii.

RESULTS: The human CA1, AQP, band-3 protein and H[+]-transport proteins revealed similar proteins in Acanthamoeba. Docking showed the binding of AZM on amoebal AQP-like proteins.  Acanthamoeba showed transient shape changes and encystation at differential doses of brinzolamide, mannitol and AZM.  Conclusion: Water and pH regulating adapter proteins in Acanthamoeba and humans show significant homology, these mechanisms evolved early in the primitive unicellular eukaryotes and have remained conserved in multicellular eukaryotes.}, } @article {pmid29322437, year = {2018}, author = {Jakobi, T and Dieterich, C}, title = {Deep Computational Circular RNA Analytics from RNA-seq Data.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1724}, number = {}, pages = {9-25}, doi = {10.1007/978-1-4939-7562-4_2}, pmid = {29322437}, issn = {1940-6029}, mesh = {Computational Biology/*methods ; *Gene Expression Regulation ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; RNA/*genetics ; RNA, Circular ; Sequence Analysis, RNA/*methods ; *Transcriptome ; }, abstract = {Circular RNAs (circRNAs) have been first described as "scrambled exons" in the 1990s. CircRNAs originate from back splicing or exon skipping of linear RNA templates and have continuously gained attention in recent years due to the availability of high-throughput whole-transcriptome sequencing methods. Numerous manuscripts describe thousands of circRNAs throughout uni- and multicellular eukaryote species and demonstrated that they are conserved, stable, and abundant in specific tissues or conditions. This manuscript provides a walk-through of our bioinformatics toolbox, which covers all aspects of in silico circRNA analysis, starting from raw sequencing data and back-splicing junction discovery to circRNA quantitation and reconstruction of internal the circRNA structure.}, } @article {pmid29320478, year = {2018}, author = {Smakowska-Luzan, E and Mott, GA and Parys, K and Stegmann, M and Howton, TC and Layeghifard, M and Neuhold, J and Lehner, A and Kong, J and Grünwald, K and Weinberger, N and Satbhai, SB and Mayer, D and Busch, W and Madalinski, M and Stolt-Bergner, P and Provart, NJ and Mukhtar, MS and Zipfel, C and Desveaux, D and Guttman, DS and Belkhadir, Y}, title = {An extracellular network of Arabidopsis leucine-rich repeat receptor kinases.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {342-346}, pmid = {29320478}, issn = {1476-4687}, support = {T 947/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Arabidopsis/cytology/*enzymology/immunology/microbiology ; Arabidopsis Proteins/*chemistry/*metabolism ; Leucine/*metabolism ; Protein Binding ; Protein Domains ; Protein Kinases/*chemistry/*metabolism ; Protein Serine-Threonine Kinases/chemistry/metabolism ; Receptors, Cell Surface/chemistry/metabolism ; Reproducibility of Results ; Signal Transduction ; }, abstract = {The cells of multicellular organisms receive extracellular signals using surface receptors. The extracellular domains (ECDs) of cell surface receptors function as interaction platforms, and as regulatory modules of receptor activation. Understanding how interactions between ECDs produce signal-competent receptor complexes is challenging because of their low biochemical tractability. In plants, the discovery of ECD interactions is complicated by the massive expansion of receptor families, which creates tremendous potential for changeover in receptor interactions. The largest of these families in Arabidopsis thaliana consists of 225 evolutionarily related leucine-rich repeat receptor kinases (LRR-RKs), which function in the sensing of microorganisms, cell expansion, stomata development and stem-cell maintenance. Although the principles that govern LRR-RK signalling activation are emerging, the systems-level organization of this family of proteins is unknown. Here, to address this, we investigated 40,000 potential ECD interactions using a sensitized high-throughput interaction assay, and produced an LRR-based cell surface interaction network (CSI[LRR]) that consists of 567 interactions. To demonstrate the power of CSI[LRR] for detecting biologically relevant interactions, we predicted and validated the functions of uncharacterized LRR-RKs in plant growth and immunity. In addition, we show that CSI[LRR] operates as a unified regulatory network in which the LRR-RKs most crucial for its overall structure are required to prevent the aberrant signalling of receptors that are several network-steps away. Thus, plants have evolved LRR-RK networks to process extracellular signals into carefully balanced responses.}, } @article {pmid29320389, year = {2018}, author = {Ćetković, H and Halasz, M and Herak Bosnar, M}, title = {Sponges: A Reservoir of Genes Implicated in Human Cancer.}, journal = {Marine drugs}, volume = {16}, number = {1}, pages = {}, pmid = {29320389}, issn = {1660-3397}, mesh = {Animals ; Evolution, Molecular ; Genome/genetics ; Humans ; Neoplasms/*genetics ; Porifera/*genetics ; Proteome/genetics ; Signal Transduction/genetics ; }, abstract = {Recently, it was shown that the majority of genes linked to human diseases, such as cancer genes, evolved in two major evolutionary transitions-the emergence of unicellular organisms and the transition to multicellularity. Therefore, it has been widely accepted that the majority of disease-related genes has already been present in species distantly related to humans. An original way of studying human diseases relies on analyzing genes and proteins that cause a certain disease using model organisms that belong to the evolutionary level at which these genes have emerged. This kind of approach is supported by the simplicity of the genome/proteome, body plan, and physiology of such model organisms. It has been established for quite some time that sponges are an ideal model system for such studies, having a vast variety of genes known to be engaged in sophisticated processes and signalling pathways associated with higher animals. Sponges are considered to be the simplest multicellular animals and have changed little during evolution. Therefore, they provide an insight into the metazoan ancestor genome/proteome features. This review compiles current knowledge of cancer-related genes/proteins in marine sponges.}, } @article {pmid29301490, year = {2018}, author = {Strader, ME and Aglyamova, GV and Matz, MV}, title = {Molecular characterization of larval development from fertilization to metamorphosis in a reef-building coral.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {17}, pmid = {29301490}, issn = {1471-2164}, support = {DEB-1501463//National Science Foundation/International ; }, mesh = {Animals ; Anthozoa/anatomy & histology/embryology/*genetics/*growth & development ; Behavior, Animal/drug effects ; Fertilization ; Larva/genetics/growth & development/metabolism ; Luminescent Proteins/metabolism ; Metamorphosis, Biological/genetics ; Transcriptome ; }, abstract = {BACKGROUND: Molecular mechanisms underlying coral larval competence, the ability of larvae to respond to settlement cues, determine their dispersal potential and are potential targets of natural selection. Here, we profiled competence, fluorescence and genome-wide gene expression in embryos and larvae of the reef-building coral Acropora millepora daily throughout 12 days post-fertilization.

RESULTS: Gene expression associated with competence was positively correlated with transcriptomic response to the natural settlement cue, confirming that mature coral larvae are "primed" for settlement. Rise of competence through development was accompanied by up-regulation of sensory and signal transduction genes such as ion channels, genes involved in neuropeptide signaling, and G-protein coupled receptor (GPCRs). A drug screen targeting components of GPCR signaling pathways confirmed a role in larval settlement behavior and metamorphosis.

CONCLUSIONS: These results gives insight into the molecular complexity underlying these transitions and reveals receptors and pathways that, if altered by changing environments, could affect dispersal capabilities of reef-building corals. In addition, this dataset provides a toolkit for asking broad questions about sensory capacity in multicellular animals and the evolution of development.}, } @article {pmid29294063, year = {2018}, author = {Featherston, J and Arakaki, Y and Hanschen, ER and Ferris, PJ and Michod, RE and Olson, BJSC and Nozaki, H and Durand, PM}, title = {The 4-Celled Tetrabaena socialis Nuclear Genome Reveals the Essential Components for Genetic Control of Cell Number at the Origin of Multicellularity in the Volvocine Lineage.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {855-870}, doi = {10.1093/molbev/msx332}, pmid = {29294063}, issn = {1537-1719}, mesh = {*Biological Evolution ; Chlorophyta/*genetics ; Cyclins/genetics ; Genes, Retinoblastoma ; *Genes, cdc ; *Genome Components ; Multigene Family ; Proteasome Endopeptidase Complex/genetics ; Selection, Genetic ; Transcriptome ; Ubiquitin/genetics ; }, abstract = {Multicellularity is the premier example of a major evolutionary transition in individuality and was a foundational event in the evolution of macroscopic biodiversity. The volvocine chlorophyte lineage is well suited for studying this process. Extant members span unicellular, simple colonial, and obligate multicellular taxa with germ-soma differentiation. Here, we report the nuclear genome sequence of one of the most morphologically simple organisms in this lineage-the 4-celled colonial Tetrabaena socialis and compare this to the three other complete volvocine nuclear genomes. Using conservative estimates of gene family expansions a minimal set of expanded gene families was identified that associate with the origin of multicellularity. These families are rich in genes related to developmental processes. A subset of these families is lineage specific, which suggests that at a genomic level the evolution of multicellularity also includes lineage-specific molecular developments. Multiple points of evidence associate modifications to the ubiquitin proteasomal pathway (UPP) with the beginning of coloniality. Genes undergoing positive or accelerating selection in the multicellular volvocines were found to be enriched in components of the UPP and gene families gained at the origin of multicellularity include components of the UPP. A defining feature of colonial/multicellular life cycles is the genetic control of cell number. The genomic data presented here, which includes diversification of cell cycle genes and modifications to the UPP, align the genetic components with the evolution of this trait.}, } @article {pmid29293210, year = {2017}, author = {Wade, J and Dyck, B and Palin, RM and Moore, JDP and Smye, AJ}, title = {The divergent fates of primitive hydrospheric water on Earth and Mars.}, journal = {Nature}, volume = {552}, number = {7685}, pages = {391-394}, pmid = {29293210}, issn = {1476-4687}, mesh = {Convection ; *Earth, Planet ; Extraterrestrial Environment/*chemistry ; Ferrous Compounds/analysis/chemistry ; Geologic Sediments/*chemistry ; Hot Temperature ; Magnetic Fields ; *Mars ; Origin of Life ; Photolysis ; Pressure ; Silicates/analysis/chemistry ; Water/*analysis/*chemistry ; }, abstract = {Despite active transport into Earth's mantle, water has been present on our planet's surface for most of geological time. Yet water disappeared from the Martian surface soon after its formation. Although some of the water on Mars was lost to space via photolysis following the collapse of the planet's magnetic field, the widespread serpentinization of Martian crust suggests that metamorphic hydration reactions played a critical part in the sequestration of the crust. Here we quantify the relative volumes of water that could be removed from each planet's surface via the burial and metamorphism of hydrated mafic crusts, and calculate mineral transition-induced bulk-density changes at conditions of elevated pressure and temperature for each. The metamorphic mineral assemblages in relatively FeO-rich Martian lavas can hold about 25 per cent more structurally bound water than those in metamorphosed terrestrial basalts, and can retain it at greater depths within Mars. Our calculations suggest that in excess of 9 per cent by volume of the Martian mantle may contain hydrous mineral species as a consequence of surface reactions, compared to about 4 per cent by volume of Earth's mantle. Furthermore, neither primitive nor evolved hydrated Martian crust show noticeably different bulk densities compared to their anhydrous equivalents, in contrast to hydrous mafic terrestrial crust, which transforms to denser eclogite upon dehydration. This would have allowed efficient overplating and burial of early Martian crust in a stagnant-lid tectonic regime, in which the lithosphere comprised a single tectonic plate, with only the warmer, lower crust involved in mantle convection. This provided an important sink for hydrospheric water and a mechanism for oxidizing the Martian mantle. Conversely, relatively buoyant mafic crust and hotter geothermal gradients on Earth reduced the potential for upper-mantle hydration early in its geological history, leading to water being retained close to its surface, and thus creating conditions conducive for the evolution of complex multicellular life.}, } @article {pmid29292130, year = {2018}, author = {López, JL and Alvarez, F and Príncipe, A and Salas, ME and Lozano, MJ and Draghi, WO and Jofré, E and Lagares, A}, title = {Isolation, taxonomic analysis, and phenotypic characterization of bacterial endophytes present in alfalfa (Medicago sativa) seeds.}, journal = {Journal of biotechnology}, volume = {267}, number = {}, pages = {55-62}, doi = {10.1016/j.jbiotec.2017.12.020}, pmid = {29292130}, issn = {1873-4863}, mesh = {Actinobacteria/genetics/isolation & purification ; Bacteroidetes/genetics/isolation & purification ; Endophytes/classification/*genetics ; Firmicutes/genetics/isolation & purification ; Medicago sativa/genetics/*microbiology ; Microbiota/*genetics ; *Phylogeny ; Proteobacteria/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Seedlings/microbiology ; Seeds/microbiology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {A growing body of evidence has reinforced the central role of microbiomes in the life of sound multicellular eukaryotes, thus more properly described as true holobionts. Though soil was considered a main source of plant microbiomes, seeds have been shown to be endophytically colonized by microorganisms thus representing natural carriers of a selected microbial inoculum to the young seedlings. In this work we have investigated the type of culturable endophytic bacteria that are carried within surface-sterilized alfalfa seeds. MALDI-TOF analysis revealed the presence of bacteria that belonged to 40 separate genera, distributed within four taxa (Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes). Nonsymbiotic members of the Rhizobiaceae family were also found. The evaluation of nine different in-vitro biochemical activities demonstrated isolates with complex combinations of traits that, upon a Principal-Component-Analysis, could be classified into four phenotypic groups. That isolates from nearly half of the genera identified had been able to colonize alfalfa plants grown under axenic conditions was remarkable. Further analyses should be addressed to investigating the colonization mechanisms of the alfalfa seeds, the evolutionary significance of the alfalfa-seed endophytes, and also how after germination the seed microbiome competes with spermospheric and rhizospheric soil bacteria to colonize newly emerging seedlings.}, } @article {pmid29288005, year = {2018}, author = {Yoshida, T and Kates, M and Sopko, NA and Liu, X and Singh, AK and Bishai, WR and Joice, G and McConkey, DJ and Bivalacqua, TJ}, title = {Ex vivo culture of tumor cells from N-methyl-N-nitrosourea-induced bladder cancer in rats: Development of organoids and an immortalized cell line.}, journal = {Urologic oncology}, volume = {36}, number = {4}, pages = {160.e23-160.e32}, doi = {10.1016/j.urolonc.2017.11.024}, pmid = {29288005}, issn = {1873-2496}, mesh = {Animals ; Carcinoma, Transitional Cell/chemically induced/*pathology ; Cell Differentiation ; Cell Line, Tumor ; Coculture Techniques ; Female ; Fibroblasts ; Humans ; Methylnitrosourea/toxicity ; Mice ; Organoids/*pathology ; Primary Cell Culture ; Rats ; Rats, Inbred F344 ; Spheroids, Cellular ; Urinary Bladder/*cytology ; Urinary Bladder Neoplasms/chemically induced/*pathology ; }, abstract = {OBJECTIVE: We ex vivo cultured primary tumor cells from N-methyl-N-nitrosourea (MNU)-induced bladder tumors in rats and established an immortalized cell line from them.

MATERIALS AND METHODS: Bladder tumors in rats were induced by instillation of MNU into the murine bladder. Primary tumor cells were prepared by the cancer-tissue originated spheroid method. An immortalized cell line was established by co-culture with fibroblasts. The cultured tumor cells were molecularly and functionally characterized by quantitative real-time polymerase chain reaction, Western blot, growth assay, and transwell migration assay.

RESULTS: Primary tumor cells were successfully prepared as multicellular spheroids from MNU-induced bladder tumors. The differentiation marker expression patterns observed in the original tumors were largely retained in the spheroids. We succeeded in establishing a cell line from the spheroids and named it T-MNU-1. Although basal markers (CK14 and CK5) were enriched in T-MNU-1 compared to the spheroids, T-MNU-1 expressed both luminal and basal markers. T-MNU-1 was able to migrate through a transwell.

CONCLUSIONS: Tumor cells in MNU-induced bladder tumors were successfully cultured ex vivo as organoids, and an immortalized cell line was also established from them. The ex vivo models offer a platform that enables analysis of intrinsic characteristics of tumor cells excluding influence of microenvironment in MNU-induced bladder tumors.}, } @article {pmid29283188, year = {2018}, author = {Peccoud, J and Cordaux, R and Gilbert, C}, title = {Analyzing Horizontal Transfer of Transposable Elements on a Large Scale: Challenges and Prospects.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {40}, number = {2}, pages = {}, doi = {10.1002/bies.201700177}, pmid = {29283188}, issn = {1521-1878}, mesh = {Animals ; DNA Transposable Elements/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Genome ; Sequence Analysis/methods ; }, abstract = {Whoever compares the genomes of distantly related species might find aberrantly high sequence similarity at certain loci. Such anomaly can only be explained by genetic material being transferred through other means than reproduction, that is, a horizontal transfer (HT). Between multicellular organisms, the transferred material will likely turn out to be a transposable element (TE). Because TEs can move between loci and invade chromosomes by replicating themselves, HT of TEs (HTT) profoundly impacts genome evolution. Yet, very few studies have quantified HTT at large taxonomic scales. Indeed, this task currently faces difficulties that range from the variable quality of available genome sequences to limitations of analytical procedures, some of which have been overlooked. Here we review the many challenges that an extensive analysis of HTT must overcome, we expose biases and limits of current methods, suggest solutions or workarounds, and reflect upon approaches that could be developed to better quantify this phenomenon.}, } @article {pmid29279310, year = {2018}, author = {Hesp, ZC and Yoseph, RY and Suzuki, R and Jukkola, P and Wilson, C and Nishiyama, A and McTigue, DM}, title = {Proliferating NG2-Cell-Dependent Angiogenesis and Scar Formation Alter Axon Growth and Functional Recovery After Spinal Cord Injury in Mice.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {38}, number = {6}, pages = {1366-1382}, pmid = {29279310}, issn = {1529-2401}, support = {R01 NS074870/NS/NINDS NIH HHS/United States ; P30 NS045758/NS/NINDS NIH HHS/United States ; F31 NS095606/NS/NINDS NIH HHS/United States ; P30 NS104177/NS/NINDS NIH HHS/United States ; R01 NS073425/NS/NINDS NIH HHS/United States ; R01 NS049267/NS/NINDS NIH HHS/United States ; R01 NS043246/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Antigens/*genetics ; Astrocytes/pathology ; Axons/*pathology ; Cell Proliferation/drug effects ; Cicatrix/*genetics/pathology ; Fibrosis/pathology ; Glial Fibrillary Acidic Protein/biosynthesis/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neovascularization, Pathologic/*genetics/pathology ; Neuroglia/metabolism/pathology ; Pericytes/metabolism/pathology ; Proteoglycans/*genetics ; Recovery of Function/genetics ; Spinal Cord Injuries/*genetics/*pathology ; }, abstract = {Spinal cord injury (SCI) induces a centralized fibrotic scar surrounded by a reactive glial scar at the lesion site. The origin of these scars is thought to be perivascular cells entering lesions on ingrowing blood vessels and reactive astrocytes, respectively. However, two NG2-expressing cell populations, pericytes and glia, may also influence scar formation. In the periphery, new blood vessel growth requires proliferating NG2[+] pericytes; if this were also true in the CNS, then the fibrotic scar would depend on dividing NG2[+] pericytes. NG2[+] glial cells (also called oligodendrocyte progenitors or polydendrocytes) also proliferate after SCI and accumulate in large numbers among astrocytes in the glial scar. Their effect there, if any, is unknown. We show that proliferating NG2[+] pericytes and glia largely segregate into the fibrotic and glial scars, respectively; therefore, we used a thymidine kinase/ganciclovir paradigm to ablate both dividing NG2[+] cell populations to determine whether either scar was altered. Results reveal that loss of proliferating NG2[+] pericytes in the lesion prevented intralesion angiogenesis and completely abolished the fibrotic scar. The glial scar was also altered in the absence of acutely dividing NG2[+] cells, displaying discontinuous borders and significantly reduced GFAP density. Collectively, these changes enhanced edema, prolonged hemorrhage, and impaired forelimb functional recovery. Interestingly, after halting GCV at 14 d postinjury, scar elements and vessels entered the lesions over the next 7 d, as did large numbers of axons that were not present in controls. Collectively, these data reveal that acutely dividing NG2[+] pericytes and glia play fundamental roles in post-SCI tissue remodeling.SIGNIFICANCE STATEMENT Spinal cord injury (SCI) is characterized by formation of astrocytic and fibrotic scars, both of which are necessary for lesion repair. NG2[+] cells may influence both scar-forming processes. This study used a novel transgenic mouse paradigm to ablate proliferating NG2[+] cells after SCI to better understand their role in repair. For the first time, our data show that dividing NG2[+] pericytes are required for post-SCI angiogenesis, which in turn is needed for fibrotic scar formation. Moreover, loss of cycling NG2[+] glia and pericytes caused significant multicellular tissue changes, including altered astrocyte responses and impaired functional recovery. This work reveals previously unknown ways in which proliferating NG2[+] cells contribute to endogenous repair after SCI.}, } @article {pmid29276774, year = {2017}, author = {Vasemägi, A and Visse, M and Kisand, V}, title = {Effect of Environmental Factors and an Emerging Parasitic Disease on Gut Microbiome of Wild Salmonid Fish.}, journal = {mSphere}, volume = {2}, number = {6}, pages = {}, pmid = {29276774}, issn = {2379-5042}, abstract = {The gastrointestinal tract (GIT) of fish supports a dynamic microbial ecosystem that is intimately linked to host nutrient acquisition, epithelial development, immune system priming, and disease prevention, and we are far from understanding the complex interactions among parasites, symbiotic gut bacteria, and host fitness. Here, we analyzed the effects of environmental factors and parasitic burdens on the microbial composition and diversity within the GIT of the brown trout (Salmo trutta). We focused on the emerging dangerous salmonid myxozoan parasite Tetracapsuloides bryosalmonae, which causes proliferative kidney disease in salmonid fish, to demonstrate the potential role of GIT micobiomes in the modulation of host-parasite relationships. The microbial diversity in the GIT displayed clear clustering according to the river of origin, while considerable variation was also found among fish from the same river. Environmental variables such as oxygen concentration, water temperature, and river morphometry strongly associated with both the river microbial community and the GIT microbiome, supporting the role of the environment in microbial assemblage and the relative insignificance of the host genotype and gender. Contrary to expectations, the parasite load exhibited a significant positive relationship with the richness of the GIT microbiome. Many operational taxonomic units (OTUs; n = 202) are more abundant in T. bryosalmonae-infected fish, suggesting that brown trout with large parasite burdens are prone to lose their GIT microbiome homeostasis. The OTUs with the strongest increase in infected trout are mostly nonpathogenic aquatic, anaerobic sediment/sludge, or ruminant bacteria. Our results underscore the significance of the interactions among parasitic disease, abiotic factors, and the GIT microbiome in disease etiology. IMPORTANCE Cohabiting microorganisms play diverse and important roles in the biology of multicellular hosts, but their diversity and interactions with abiotic and biotic factors remain largely unsurveyed. Nevertheless, it is becoming increasingly clear that many properties of host phenotypes reflect contributions from the associated microbiome. We focus on a question of how parasites, the host genetic background, and abiotic factors influence the microbiome in salmonid hosts by using a host-parasite model consisting of wild brown trout (Salmo trutta) and the myxozoan Tetracapsuloides bryosalmonae, which causes widely distributed proliferative kidney disease. We show that parasite infection increases the frequency of bacteria from the surrounding river water community, reflecting impaired homeostasis in the fish gut. Our results also demonstrate the importance of abiotic environmental factors and host size in the assemblage of the gut microbiome of fish and the relative insignificance of the host genotype and gender.}, } @article {pmid29269894, year = {2017}, author = {Liu, J and Zhang, W and Li, X and Li, X and Chen, X and Li, JH and Teng, Z and Xu, C and Santini, CL and Zhao, L and Zhao, Y and Zhang, H and Zhang, WJ and Xu, K and Li, C and Pan, Y and Xiao, T and Pan, H and Wu, LF}, title = {Bacterial community structure and novel species of magnetotactic bacteria in sediments from a seamount in the Mariana volcanic arc.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {17964}, pmid = {29269894}, issn = {2045-2322}, mesh = {Bacteria/genetics/metabolism ; Geologic Sediments/*microbiology ; Magnetosomes ; Magnetospirillum/genetics/*metabolism ; Microbiota/genetics ; Micronesia ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Seamounts are undersea mountains rising abruptly from the sea floor and interacting dynamically with underwater currents. They represent unique biological habitats with various microbial community structures. Certain seamount bacteria form conspicuous extracellular iron oxide structures, including encrusted stalks, flattened bifurcating tubes, and filamentous sheaths. To extend our knowledge of seamount ecosystems, we performed an integrated study on population structure and the occurrence of magnetotactic bacteria (MTB) that synthesize intracellular iron oxide nanocrystals in sediments of a seamount in the Mariana volcanic arc. We found Proteobacteria dominant at 13 of 14 stations, but ranked second in abundance to members of the phylum Firmicutes at the deep-water station located on a steep slope facing the Mariana-Yap Trench. Live MTB dwell in biogenic sediments from all 14 stations ranging in depth from 238 to 2,023 m. Some magnetotactic cocci possess the most complex flagellar apparatus yet reported; 19 flagella are arranged in a 3:4:5:4:3 array within a flagellar bundle. Phylogenetic analysis of 16S rRNA gene sequences identified 16 novel species of MTB specific to this seamount. Together the results obtained indicate that geographic properties of the seamount stations are important in shaping the bacterial community structure and the MTB composition.}, } @article {pmid29260254, year = {2018}, author = {Böttcher, T}, title = {From Molecules to Life: Quantifying the Complexity of Chemical and Biological Systems in the Universe.}, journal = {Journal of molecular evolution}, volume = {86}, number = {1}, pages = {1-10}, pmid = {29260254}, issn = {1432-1432}, support = {Emmy Noether//DFG/International ; Marie Curie Zukunftskolleg Incoming Fellowship//EU FP7/International ; }, mesh = {*Biological Evolution ; Earth, Planet ; Eukaryotic Cells ; *Evolution, Chemical ; Evolution, Molecular ; Life ; Models, Biological ; Models, Statistical ; *Origin of Life ; Prokaryotic Cells ; }, abstract = {Life is a complex phenomenon and much research has been devoted to both understanding its origins from prebiotic chemistry and discovering life beyond Earth. Yet, it has remained elusive how to quantify this complexity and how to compare chemical and biological units on one common scale. Here, a mathematical description of molecular complexity was applied allowing to quantitatively assess complexity of chemical structures. This in combination with the orthogonal measure of information complexity resulted in a two-dimensional complexity space ranging over the entire spectrum from molecules to organisms. Entities with a certain level of information complexity directly require a functionally complex mechanism for their production or replication and are hence indicative for life-like systems. In order to describe entities combining molecular and information complexity, the term biogenic unit was introduced. Exemplified biogenic unit complexities were calculated for ribozymes, protein enzymes, multimeric protein complexes, and even an entire virus particle. Complexities of prokaryotic and eukaryotic cells, as well as multicellular organisms, were estimated. Thereby distinct evolutionary stages in complexity space were identified. The here developed approach to compare the complexity of biogenic units allows for the first time to address the gradual characteristics of prebiotic and life-like systems without the need for a definition of life. This operational concept may guide our search for life in the Universe, and it may direct the investigations of prebiotic trajectories that lead towards the evolution of complexity at the origins of life.}, } @article {pmid29259597, year = {2017}, author = {Iakobachvili, N and Peters, PJ}, title = {Humans in a Dish: The Potential of Organoids in Modeling Immunity and Infectious Diseases.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {2402}, pmid = {29259597}, issn = {1664-302X}, abstract = {For many decades, human infectious diseases have been studied in immortalized cell lines, isolated primary cells from blood and a range of animal hosts. This research has been of fundamental importance in advancing our understanding of host and pathogen responses but remains limited by the absence of multicellular context and inherent differences in animal immune systems that result in altered immune responses. Recent developments in stem cell biology have led to the in vitro growth of organoids that faithfully recapitulate a variety of human tissues including lung, intestine and brain amongst many others. Organoids are derived from human stem cells and retain the genomic background, cellular organization and functionality of their tissue of origin. Thus they have been widely used to characterize stem cell development, numerous cancers and genetic diseases. We believe organoid technology can be harnessed to study host-pathogen interactions resulting in a more physiologically relevant model that yields more predictive data of human infectious diseases than current systems. Here, we highlight recent work and discuss the potential of human stem cell-derived organoids in studying infectious diseases and immunity.}, } @article {pmid29251593, year = {2017}, author = {Molaro, A and Malik, HS}, title = {Culture shock.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {29251593}, issn = {2050-084X}, mesh = {Cell Line ; *Dosage Compensation, Genetic ; Humans ; *Sex Chromosomes ; }, abstract = {Many different human cell lines, including both normal and cancer cells, appear to converge to a state that contains an unusual number of chromosomes when they are grown in culture.}, } @article {pmid29251591, year = {2017}, author = {Xu, J and Peng, X and Chen, Y and Zhang, Y and Ma, Q and Liang, L and Carter, AC and Lu, X and Wu, CI}, title = {Free-living human cells reconfigure their chromosomes in the evolution back to uni-cellularity.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {29251591}, issn = {2050-084X}, mesh = {*Adaptation, Biological ; Cell Line, Tumor ; *Cell Proliferation ; *Chromosomes, Human ; Evolution, Molecular ; Humans ; Karyotype ; *Sex Chromosomes ; }, abstract = {Cells of multi-cellular organisms evolve toward uni-cellularity in the form of cancer and, if humans intervene, continue to evolve in cell culture. During this process, gene dosage relationships may evolve in novel ways to cope with the new environment and may regress back to the ancestral uni-cellular state. In this context, the evolution of sex chromosomes vis-a-vis autosomes is of particular interest. Here, we report the chromosomal evolution in ~ 600 cancer cell lines. Many of them jettisoned either Y or the inactive X; thus, free-living male and female cells converge by becoming 'de-sexualized'. Surprisingly, the active X often doubled, accompanied by the addition of one haploid complement of autosomes, leading to an X:A ratio of 2:3 from the extant ratio of 1:2. Theoretical modeling of the frequency distribution of X:A karyotypes suggests that the 2:3 ratio confers a higher fitness and may reflect aspects of sex chromosome evolution.}, } @article {pmid29245010, year = {2017}, author = {Kundu, P and Blacher, E and Elinav, E and Pettersson, S}, title = {Our Gut Microbiome: The Evolving Inner Self.}, journal = {Cell}, volume = {171}, number = {7}, pages = {1481-1493}, doi = {10.1016/j.cell.2017.11.024}, pmid = {29245010}, issn = {1097-4172}, mesh = {Aging ; Animals ; Bacteria/classification/*growth & development/metabolism ; Biological Evolution ; *Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; Organ Specificity ; Puberty ; Symbiosis ; }, abstract = {The "holobiont" concept, defined as the collective contribution of the eukaryotic and prokaryotic counterparts to the multicellular organism, introduces a complex definition of individuality enabling a new comprehensive view of human evolution and personalized characteristics. Here, we provide snapshots of the evolving microbial-host associations and relations during distinct milestones across the lifespan of a human being. We discuss the current knowledge of biological symbiosis between the microbiome and its host and portray the challenges in understanding these interactions and their potential effects on human physiology, including microbiome-nervous system inter-relationship and its relevance to human variation and individuality.}, } @article {pmid29225309, year = {2017}, author = {Jong, LW and Fujiwara, T and Nozaki, H and Miyagishima, SY}, title = {Cell size for commitment to cell division and number of successive cell divisions in multicellular volvocine green algae Tetrabaena socialis and Gonium pectorale.}, journal = {Proceedings of the Japan Academy. Series B, Physical and biological sciences}, volume = {93}, number = {10}, pages = {832-840}, pmid = {29225309}, issn = {1349-2896}, mesh = {Cell Count/methods ; Cell Culture Techniques/methods ; Cell Division ; Cell Size ; Chlorophyta/*cytology ; Electrophoresis, Polyacrylamide Gel/methods ; }, abstract = {Volvocine algae constitute a green algal lineage comprising unicellular Chlamydomonas, four-celled Tetrabaena, eight to 32-celled Gonium, and others up to Volvox spp., which consist of up to 50,000 cells. These algae proliferate by multiple fissions with cellular growth up to several fold in size and subsequent successive cell divisions. Chlamydomonas reinhardtii cells produce two to 32 daughter cells by one to five divisions, depending on cellular growth in the G1 phase. By contrast, in this study, we found that Tetrabaena socialis and Gonium pectorale cells mostly produced four and eight daughter cells by two and three successive divisions, respectively. In contrast to C. reinhardtii, which is committed to cell division when the cell has grown two-fold, T. socialis and G. pectorale are committed only when the cells have grown four- and eight-fold, respectively. Thus, our results suggest that evolutionary changes in cellular size for commitment largely contributes to the emergence and evolution of multicellularity in volvocine algae.}, } @article {pmid29219578, year = {2017}, author = {Varennes, J and Fancher, S and Han, B and Mugler, A}, title = {Emergent versus Individual-Based Multicellular Chemotaxis.}, journal = {Physical review letters}, volume = {119}, number = {18}, pages = {188101}, doi = {10.1103/PhysRevLett.119.188101}, pmid = {29219578}, issn = {1079-7114}, mesh = {*Cell Movement ; *Chemotaxis ; *Models, Biological ; }, abstract = {Multicellular chemotaxis can occur via individually chemotaxing cells that are mechanically coupled. Alternatively, it can emerge collectively, from cells chemotaxing differently in a group than they would individually. Here we consider collective movement that emerges from cells on the exterior of the collective responding to chemotactic signals, whereas bulk cells remain uninvolved in sensing and directing the collective. We find that the precision of this type of emergent chemotaxis is higher than that of individual-based chemotaxis for one-dimensional cell chains and two-dimensional cell sheets, but not three-dimensional cell clusters. We describe the physical origins of these results, discuss their biological implications, and show how they can be tested using common experimental measures such as the chemotactic index.}, } @article {pmid29212441, year = {2017}, author = {Arakaki, Y and Fujiwara, T and Kawai-Toyooka, H and Kawafune, K and Featherston, J and Durand, PM and Miyagishima, SY and Nozaki, H}, title = {Evolution of cytokinesis-related protein localization during the emergence of multicellularity in volvocine green algae.}, journal = {BMC evolutionary biology}, volume = {17}, number = {1}, pages = {243}, pmid = {29212441}, issn = {1471-2148}, support = {2016-B//NIG-JOINT/International ; 25-9234//Japan Society for the Promotion of Science/International ; 16H02518//Japan Society for the Promotion of Science/International ; RA151217156515//National Research Foundation/International ; }, mesh = {Algal Proteins/*genetics ; Cytokinesis/*genetics ; *Evolution, Molecular ; Likelihood Functions ; Models, Biological ; Phylogeny ; Protein Transport ; Species Specificity ; Subcellular Fractions/metabolism ; Volvox/*cytology/*genetics ; }, abstract = {BACKGROUND: The volvocine lineage, containing unicellular Chlamydomonas reinhardtii and differentiated multicellular Volvox carteri, is a powerful model for comparative studies aiming at understanding emergence of multicellularity. Tetrabaena socialis is the simplest multicellular volvocine alga and belongs to the family Tetrabaenaceae that is sister to more complex multicellular volvocine families, Goniaceae and Volvocaceae. Thus, T. socialis is a key species to elucidate the initial steps in the evolution of multicellularity. In the asexual life cycle of C. reinhardtii and multicellular volvocine species, reproductive cells form daughter cells/colonies by multiple fission. In embryogenesis of the multicellular species, daughter protoplasts are connected to one another by cytoplasmic bridges formed by incomplete cytokinesis during multiple fission. These bridges are important for arranging the daughter protoplasts in appropriate positions such that species-specific integrated multicellular individuals are shaped. Detailed comparative studies of cytokinesis between unicellular and simple multicellular volvocine species will help to elucidate the emergence of multicellularity from the unicellular ancestor. However, the cytokinesis-related genes between closely related unicellular and multicellular species have not been subjected to a comparative analysis.

RESULTS: Here we focused on dynamin-related protein 1 (DRP1), which is known for its role in cytokinesis in land plants. Immunofluorescence microscopy using an antibody against T. socialis DRP1 revealed that volvocine DRP1 was localized to division planes during cytokinesis in unicellular C. reinhardtii and two simple multicellular volvocine species T. socialis and Gonium pectorale. DRP1 signals were mainly observed in the newly formed division planes of unicellular C. reinhardtii during multiple fission, whereas in multicellular T. socialis and G. pectorale, DRP1 signals were observed in all division planes during embryogenesis.

CONCLUSIONS: These results indicate that the molecular mechanisms of cytokinesis may be different in unicellular and multicellular volvocine algae. The localization of DRP1 during multiple fission might have been modified in the common ancestor of multicellular volvocine algae. This modification may have been essential for the re-orientation of cells and shaping colonies during the emergence of multicellularity in this lineage.}, } @article {pmid29208647, year = {2018}, author = {Matt, GY and Umen, JG}, title = {Cell-Type Transcriptomes of the Multicellular Green Alga Volvox carteri Yield Insights into the Evolutionary Origins of Germ and Somatic Differentiation Programs.}, journal = {G3 (Bethesda, Md.)}, volume = {8}, number = {2}, pages = {531-550}, pmid = {29208647}, issn = {2160-1836}, support = {P30 CA091842/CA/NCI NIH HHS/United States ; R01 GM078376/GM/NIGMS NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {Algal Proteins/classification/genetics ; Cell Differentiation/*genetics ; Energy Metabolism/genetics ; *Evolution, Molecular ; *Gene Expression Profiling ; Gene Ontology ; Light-Harvesting Protein Complexes/classification/genetics ; Phylogeny ; Volvox/cytology/*genetics/metabolism ; }, abstract = {Germ-soma differentiation is a hallmark of complex multicellular organisms, yet its origins are not well understood. Volvox carteri is a simple multicellular green alga that has recently evolved a simple germ-soma dichotomy with only two cell-types: large germ cells called gonidia and small terminally differentiated somatic cells. Here, we provide a comprehensive characterization of the gonidial and somatic transcriptomes of V. carteri to uncover fundamental differences between the molecular and metabolic programming of these cell-types. We found extensive transcriptome differentiation between cell-types, with somatic cells expressing a more specialized program overrepresented in younger, lineage-specific genes, and gonidial cells expressing a more generalist program overrepresented in more ancient genes that shared striking overlap with stem cell-specific genes from animals and land plants. Directed analyses of different pathways revealed a strong dichotomy between cell-types with gonidial cells expressing growth-related genes and somatic cells expressing an altruistic metabolic program geared toward the assembly of flagella, which support organismal motility, and the conversion of storage carbon to sugars, which act as donors for production of extracellular matrix (ECM) glycoproteins whose secretion enables massive organismal expansion. V. carteri orthologs of diurnally controlled genes from C. reinhardtii, a single-celled relative, were analyzed for cell-type distribution and found to be strongly partitioned, with expression of dark-phase genes overrepresented in somatic cells and light-phase genes overrepresented in gonidial cells- a result that is consistent with cell-type programs in V. carteri arising by cooption of temporal regulons in a unicellular ancestor. Together, our findings reveal fundamental molecular, metabolic, and evolutionary mechanisms that underlie the origins of germ-soma differentiation in V. carteri and provide a template for understanding the acquisition of germ-soma differentiation in other multicellular lineages.}, } @article {pmid29198427, year = {2018}, author = {Kenny, NJ and de Goeij, JM and de Bakker, DM and Whalen, CG and Berezikov, E and Riesgo, A}, title = {Towards the identification of ancestrally shared regenerative mechanisms across the Metazoa: A Transcriptomic case study in the Demosponge Halisarca caerulea.}, journal = {Marine genomics}, volume = {37}, number = {}, pages = {135-147}, doi = {10.1016/j.margen.2017.11.001}, pmid = {29198427}, issn = {1876-7478}, mesh = {Animals ; *Evolution, Molecular ; Porifera/genetics/*physiology ; Regeneration/*genetics ; Time Factors ; *Transcriptome ; }, abstract = {Regeneration is an essential process for all multicellular organisms, allowing them to recover effectively from internal and external injury. This process has been studied extensively in a medical context in vertebrates, with pathways often investigated mechanistically, both to derive increased understanding and as potential drug targets for therapy. Several species from other parts of the metazoan tree of life, including Hydra, planarians and echinoderms, noted for their regenerative capabilities, have previously been targeted for study. Less well-documented for their regenerative abilities are sponges. This is surprising, as they are both one of the earliest-branching extant metazoan phyla on Earth, and are rapidly able to respond to injury. Their sessile lifestyle, lack of an external protective layer, inability to respond to predation and filter-feeding strategy all mean that regeneration is often required. In particular the demosponge genus Halisarca has been noted for its fast cell turnover and ability to quickly adjust its cell kinetic properties to repair damage through regeneration. However, while the rate and structure of regeneration in sponges has begun to be investigated, the molecular mechanisms behind this ability are yet to be catalogued. Here we describe the assembly of a reference transcriptome for Halisarca caerulea, along with additional transcriptomes noting response to injury before, shortly following (2h post-), and 12h after trauma. RNAseq reads were assembled using Trinity, annotated, and samples compared, to allow initial insight into the transcriptomic basis of sponge regenerative processes. These resources are deep, with our reference assembly containing >92.6% of the BUSCO Metazoa set of genes, and well-assembled (N50s of 836, 957, 1688 and 2032 for untreated, 2h, 12h and reference transcriptomes respectively), and therefore represent excellent qualitative resources as a bedrock for future study. The generation of transcriptomic resources from sponges before and following deliberate damage has allowed us to study particular pathways within this species responsible for repairing damage. We note particularly the involvement of the Wnt cascades in this process in this species, and detail the contents of this cascade, along with cell cycle, extracellular matrix and apoptosis-linked genes in this work. This resource represents an initial starting point for the continued development of this knowledge, given H. caerulea's ability to regenerate and position as an outgroup for comparing the process of regeneration across metazoan lineages. With this resource in place, we can begin to infer the regenerative capacity of the common ancestor of all extant animal life, and unravel the elements of regeneration in an often-overlooked clade.}, } @article {pmid29191225, year = {2017}, author = {Sanfilippo, P and Wen, J and Lai, EC}, title = {Landscape and evolution of tissue-specific alternative polyadenylation across Drosophila species.}, journal = {Genome biology}, volume = {18}, number = {1}, pages = {229}, pmid = {29191225}, issn = {1474-760X}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30-CA008748//National Cancer Institute/ ; R01 NS083833/NS/NINDS NIH HHS/United States ; R01-GM083300//National Institute of General Medical Sciences/ ; R01-NS083833//National Institute of Neurological Disorders and Stroke/ ; R01 GM083300/GM/NIGMS NIH HHS/United States ; }, mesh = {*3' Untranslated Regions ; Animals ; Cell Line ; Computational Biology/methods ; Drosophila/embryology/*genetics ; Drosophila melanogaster/genetics ; *Evolution, Molecular ; Molecular Sequence Annotation ; Organ Specificity/genetics ; *Poly A ; Polyadenylation ; RNA Isoforms ; RNA-Binding Proteins/metabolism ; Species Specificity ; *Transcription, Genetic ; }, abstract = {BACKGROUND: Drosophila melanogaster has one of best-described transcriptomes of any multicellular organism. Nevertheless, the paucity of 3'-sequencing data in this species precludes comprehensive assessment of alternative polyadenylation (APA), which is subject to broad tissue-specific control.

RESULTS: Here, we generate deep 3'-sequencing data from 23 developmental stages, tissues, and cell lines of D. melanogaster, yielding a comprehensive atlas of ~ 62,000 polyadenylated ends. These data broadly extend the annotated transcriptome, identify ~ 40,000 novel 3' termini, and reveal that two-thirds of Drosophila genes are subject to APA. Furthermore, we dramatically expand the numbers of genes known to be subject to tissue-specific APA, such as 3' untranslated region (UTR) lengthening in head and 3' UTR shortening in testis, and characterize new tissue and developmental 3' UTR patterns. Our thorough 3' UTR annotations permit reassessment of post-transcriptional regulatory networks, via conserved miRNA and RNA binding protein sites. To evaluate the evolutionary conservation and divergence of APA patterns, we generate developmental and tissue-specific 3'-seq libraries from Drosophila yakuba and Drosophila virilis. We document broadly analogous tissue-specific APA trends in these species, but also observe significant alterations in 3' end usage across orthologs. We exploit the population of functionally evolving poly(A) sites to gain clear evidence that evolutionary divergence in core polyadenylation signal (PAS) and downstream sequence element (DSE) motifs drive broad alterations in 3' UTR isoform expression across the Drosophila phylogeny.

CONCLUSIONS: These data provide a critical resource for the Drosophila community and offer many insights into the complex control of alternative tissue-specific 3' UTR formation and its consequences for post-transcriptional regulatory networks.}, } @article {pmid29179763, year = {2017}, author = {Klein, B and Wibberg, D and Hallmann, A}, title = {Whole transcriptome RNA-Seq analysis reveals extensive cell type-specific compartmentalization in Volvox carteri.}, journal = {BMC biology}, volume = {15}, number = {1}, pages = {111}, pmid = {29179763}, issn = {1741-7007}, mesh = {*Biological Evolution ; Computational Biology ; Gene Expression Profiling ; *Genome ; Sequence Analysis, RNA ; *Transcriptome ; Volvox/*genetics ; }, abstract = {BACKGROUND: One of evolution's most important achievements is the development and radiation of multicellular organisms with different types of cells. Complex multicellularity has evolved several times in eukaryotes; yet, in most lineages, an investigation of its molecular background is considerably challenging since the transition occurred too far in the past and, in addition, these lineages evolved a large number of cell types. However, for volvocine green algae, such as Volvox carteri, multicellularity is a relatively recent innovation. Furthermore, V. carteri shows a complete division of labor between only two cell types - small, flagellated somatic cells and large, immotile reproductive cells. Thus, V. carteri provides a unique opportunity to study multicellularity and cellular differentiation at the molecular level.

RESULTS: This study provides a whole transcriptome RNA-Seq analysis of separated cell types of the multicellular green alga V. carteri f. nagariensis to reveal cell type-specific components and functions. To this end, 246 million quality filtered reads were mapped to the genome and valid expression data were obtained for 93% of the 14,247 gene loci. In the subsequent search for protein domains with assigned molecular function, we identified 9435 previously classified domains in 44% of all gene loci. Furthermore, in 43% of all gene loci we identified 15,254 domains that are involved in biological processes. All identified domains were investigated regarding cell type-specific expression. Moreover, we provide further insight into the expression pattern of previously described gene families (e.g., pherophorin, extracellular matrix metalloprotease, and VARL families). Our results demonstrate an extensive compartmentalization of the transcriptome between cell types: More than half of all genes show a clear difference in expression between somatic and reproductive cells.

CONCLUSIONS: This study constitutes the first transcriptome-wide RNA-Seq analysis of separated cell types of V. carteri focusing on gene expression. The high degree of differential expression indicates a strong differentiation of cell types despite the fact that V. carteri diverged relatively recently from its unicellular relatives. Our expression dataset and the bioinformatic analyses provide the opportunity to further investigate and understand the mechanisms of cell type-specific expression and its transcriptional regulation.}, } @article {pmid29175233, year = {2018}, author = {Miller, WB}, title = {Biological information systems: Evolution as cognition-based information management.}, journal = {Progress in biophysics and molecular biology}, volume = {134}, number = {}, pages = {1-26}, doi = {10.1016/j.pbiomolbio.2017.11.005}, pmid = {29175233}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Cells/cytology/metabolism ; Cognition ; Humans ; }, abstract = {An alternative biological synthesis is presented that conceptualizes evolutionary biology as an epiphenomenon of integrated self-referential information management. Since all biological information has inherent ambiguity, the systematic assessment of information is required by living organisms to maintain self-identity and homeostatic equipoise in confrontation with environmental challenges. Through their self-referential attachment to information space, cells are the cornerstone of biological action. That individualized assessment of information space permits self-referential, self-organizing niche construction. That deployment of information and its subsequent selection enacted the dominant stable unicellular informational architectures whose biological expressions are the prokaryotic, archaeal, and eukaryotic unicellular forms. Multicellularity represents the collective appraisal of equivocal environmental information through a shared information space. This concerted action can be viewed as systematized information management to improve information quality for the maintenance of preferred homeostatic boundaries among the varied participants. When reiterated in successive scales, this same collaborative exchange of information yields macroscopic organisms as obligatory multicellular holobionts. Cognition-Based Evolution (CBE) upholds that assessment of information precedes biological action, and the deployment of information through integrative self-referential niche construction and natural cellular engineering antecedes selection. Therefore, evolutionary biology can be framed as a complex reciprocating interactome that consists of the assessment, communication, deployment and management of information by self-referential organisms at multiple scales in continuous confrontation with environmental stresses.}, } @article {pmid29170260, year = {2018}, author = {Swafford, AJM and Oakley, TH}, title = {Multimodal sensorimotor system in unicellular zoospores of a fungus.}, journal = {The Journal of experimental biology}, volume = {221}, number = {Pt 2}, pages = {}, doi = {10.1242/jeb.163196}, pmid = {29170260}, issn = {1477-9145}, mesh = {Allomyces/*physiology ; *Chemotaxis ; *Phototaxis ; Sensation ; Spores, Fungal/*physiology ; }, abstract = {Complex sensory systems often underlie critical behaviors, including avoiding predators and locating prey, mates and shelter. Multisensory systems that control motor behavior even appear in unicellular eukaryotes, such as Chlamydomonas, which are important laboratory models for sensory biology. However, we know of no unicellular opisthokonts that control motor behavior using a multimodal sensory system. Therefore, existing single-celled models for multimodal sensorimotor integration are very distantly related to animals. Here, we describe a multisensory system that controls the motor function of unicellular fungal zoospores. We found that zoospores of Allomyces arbusculus exhibit both phototaxis and chemotaxis. Furthermore, we report that closely related Allomyces species respond to either the chemical or the light stimuli presented in this study, not both, and likely do not share this multisensory system. This diversity of sensory systems within Allomyces provides a rare example of a comparative framework that can be used to examine the evolution of sensory systems following the gain/loss of available sensory modalities. The tractability of Allomyces and related fungi as laboratory organisms will facilitate detailed mechanistic investigations into the genetic underpinnings of novel photosensory systems, and how multisensory systems may have functioned in early opisthokonts before multicellularity allowed for the evolution of specialized cell types.}, } @article {pmid29166656, year = {2017}, author = {Pichugin, Y and Peña, J and Rainey, PB and Traulsen, A}, title = {Fragmentation modes and the evolution of life cycles.}, journal = {PLoS computational biology}, volume = {13}, number = {11}, pages = {e1005860}, pmid = {29166656}, issn = {1553-7358}, mesh = {Animals ; Bacteria/cytology ; *Biological Evolution ; Cell Physiological Phenomena/*physiology ; Computational Biology ; Life Cycle Stages/*physiology ; *Models, Biological ; Reproduction/physiology ; }, abstract = {Reproduction is a defining feature of living systems. To reproduce, aggregates of biological units (e.g., multicellular organisms or colonial bacteria) must fragment into smaller parts. Fragmentation modes in nature range from binary fission in bacteria to collective-level fragmentation and the production of unicellular propagules in multicellular organisms. Despite this apparent ubiquity, the adaptive significance of fragmentation modes has received little attention. Here, we develop a model in which groups arise from the division of single cells that do not separate but stay together until the moment of group fragmentation. We allow for all possible fragmentation patterns and calculate the population growth rate of each associated life cycle. Fragmentation modes that maximise growth rate comprise a restrictive set of patterns that include production of unicellular propagules and division into two similar size groups. Life cycles marked by single-cell bottlenecks maximise population growth rate under a wide range of conditions. This surprising result offers a new evolutionary explanation for the widespread occurrence of this mode of reproduction. All in all, our model provides a framework for exploring the adaptive significance of fragmentation modes and their associated life cycles.}, } @article {pmid29162942, year = {2017}, author = {Lin, H and Kazlauskas, RJ and Travisano, M}, title = {Developmental evolution facilitates rapid adaptation.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {15891}, pmid = {29162942}, issn = {2045-2322}, abstract = {Developmental evolution has frequently been identified as a mode for rapid adaptation, but direct observations of the selective benefits and associated mechanisms of developmental evolution are necessarily challenging to obtain. Here we show rapid evolution of greatly increased rates of dispersal by developmental changes when populations experience stringent selection. Replicate populations of the filamentous fungus Trichoderma citrinoviride underwent 85 serial transfers, under conditions initially favoring growth but not dispersal. T. citrinoviride populations shifted away from multicellular growth toward increased dispersal by producing one thousand times more single-celled asexual conidial spores, three times sooner than the ancestral genotype. Conidia of selected lines also germinated fifty percent faster. Gene expression changed substantially between the ancestral and selected fungi, especially for spore production and growth, demonstrating rapid evolution of tight regulatory control for down-regulation of growth and up-regulation of conidia production between 18 and 24 hours of growth. These changes involved both developmentally fixed and plastic changes in gene expression, showing that complex developmental changes can serve as a mechanism for rapid adaptation.}, } @article {pmid29152201, year = {2017}, author = {Witting, L}, title = {The natural selection of metabolism and mass selects lifeforms from viruses to multicellular animals.}, journal = {Ecology and evolution}, volume = {7}, number = {21}, pages = {9098-9118}, pmid = {29152201}, issn = {2045-7758}, abstract = {I show that the natural selection of metabolism and mass can select for the major life-history and allometric transitions that define lifeforms from viruses, over prokaryotes and larger unicells, to multicellular animals. The proposed selection is driven by a mass-specific metabolism that is selected as the pace of the resource handling that generates net energy for self-replication. An initial selection of mass is given by a dependence of mass-specific metabolism on mass in replicators that are close to a lower size limit. A sublinear maximum dependence selects for virus-like replicators, with no intrinsic metabolism, no cell, and practically no mass. A superlinear dependence selects for prokaryote-like self-replicating cells, with asexual reproduction and incomplete metabolic pathways. These self-replicators have selection for increased net energy, and this generates a gradual unfolding of population-dynamic feed-back selection from interactive competition. The incomplete feed-back selects for larger unicells with more developed metabolic pathways, and the completely developed feed-back for multicellular animals with sexual reproduction. This model unifies the natural selection of lifeforms from viruses to multicellular animals, and it provides a parsimonious explanation where allometries and major life histories evolve from the natural selection of metabolism and mass.}, } @article {pmid29149403, year = {2017}, author = {Xoconostle-Cázares, B and Ruiz-Medrano, R}, title = {Structure-Function Relationship of TCTP.}, journal = {Results and problems in cell differentiation}, volume = {64}, number = {}, pages = {47-68}, doi = {10.1007/978-3-319-67591-6_3}, pmid = {29149403}, issn = {0080-1844}, mesh = {Agriculture ; Amino Acid Sequence ; Animals ; Arabidopsis Proteins/*chemistry/genetics/*metabolism ; Biomarkers, Tumor/*chemistry/genetics/*metabolism ; Biomedical Research ; Humans ; Microtubule-Associated Proteins/*chemistry/genetics/*metabolism ; RNA, Messenger/genetics/metabolism ; Structure-Activity Relationship ; Tumor Protein, Translationally-Controlled 1 ; }, abstract = {The translationally controlled tumor protein (TCTP) is a small, multifunctional protein found in most, if not all, eukaryotic lineages, involved in a myriad of key regulatory processes. Among these, the control of proliferation and inhibition of cell death, as well as differentiation, are the most important, and it is probable that other responses are derived from the ability of TCTP to influence them in both unicellular and multicellular organisms. In the latter, an additional function for TCTP stems from its capacity to be secreted via a nonclassical pathway and function in a non-cell autonomous (paracrine) manner, thus affecting the responses of neighboring or distant cells to developmental or environmental stimuli (as in the case of serum TCTP/histamine-releasing factor in mammals and phloem TCTP in Arabidopsis). The additional ability to traverse membranes without a requirement for transmembrane receptors adds to its functional flexibility. The long-distance transport of TCTP mRNA and protein in plants via the vascular system supports the notion that an important aspect of TCTP function is its ability to influence the response of neighboring and distant cells to endogenous and exogenous signals in a supracellular manner. The predicted tridimensional structure of TCTPs indicates a high degree of conservation, more than its amino acid sequence similarity could suggest. However, subtle differences in structure could lead to different activities, as evidenced by TCTPs secreted by Plasmodium spp. Similar structural variations in animal and plant TCTPs, likely the result of convergent evolution, could lead to deviations from the canonical function of this group of proteins, which could have an impact from a biomedical and agricultural perspectives.}, } @article {pmid29147724, year = {2018}, author = {Zhu, H and Sun, X and Zhang, Q and Song, P and Hu, Q and Zhang, X and Li, X and Hu, J and Pan, J and Sun, S and Weng, Y and Yang, L}, title = {GLABROUS (CmGL) encodes a HD-ZIP IV transcription factor playing roles in multicellular trichome initiation in melon.}, journal = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik}, volume = {131}, number = {3}, pages = {569-579}, pmid = {29147724}, issn = {1432-2242}, support = {31601776//National Natural Science Foundation of China/ ; }, mesh = {Chromosome Mapping ; Cucumis melo/*genetics/growth & development ; Genes, Plant ; Genetic Linkage ; Genetic Markers ; *Leucine Zippers ; Plant Proteins/*genetics ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Transcription Factors/*genetics ; Trichomes/*growth & development ; }, abstract = {Map-based cloning identified CmGL that encodes a HD-ZIP type IV transcription factor that controls multicellular trichome initiation in melon. Trichomes are small hairs covering the aerial parts of plants that originate from the epidermal cells, which can protect plants against the damage by insects and pathogens. The regulatory pathway of unicellular trichomes has been well studied in the model plant Arabidopsis. Little is known about the genetic control and regulation of trichome development in melon (Cucumis melo L.) which has multicellular trichomes. In this study, we identified a melon mutant, cmgl, which showed completely glabrous on all aerial organs. A bulked segregant analysis was conducted to identify polymorphic markers for linkage analysis in a population with 256 F2 plants, which allowed to locate the cmgl locus in melon chromosome VIII. Next-generation sequencing-aided marker discovery and fine mapping in a large population with 1536 F2 plants narrowed the candidate gene region to 12 kb that harbored only one candidate gene for cmgl, which encoded a class IV homeodomain-associated leucine zipper transcription factor. Four SNPs in the coding region of the CmGL gene were identified between the two parental lines; a single base substitution from C to A resulted in a premature termination codon and a truncated protein in the cmgl. The SNP was converted into a dCAPS marker, which showed co-segregation in the F2 population and 564 melon accessions. Result of this study will be helpful for better understanding of genetic control of trichome development in melon and marker-assisted selection in developing new cultivars.}, } @article {pmid29141015, year = {2017}, author = {Bozler, J and Kacsoh, BZ and Bosco, G}, title = {Nematocytes: Discovery and characterization of a novel anculeate hemocyte in Drosophila falleni and Drosophila phalerata.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0188133}, pmid = {29141015}, issn = {1932-6203}, support = {DP1 MH110234/MH/NIMH NIH HHS/United States ; P30 CA023108/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Drosophila/*classification/immunology ; *Hemocytes ; Immunity, Innate ; Microscopy, Fluorescence ; Phylogeny ; Species Specificity ; }, abstract = {Immune challenges, such as parasitism, can be so pervasive and deleterious that they constitute an existential threat to a species' survival. In response to these ecological pressures, organisms have developed a wide array of novel behavioral, cellular, and molecular adaptations. Research into these immune defenses in model systems has resulted in a revolutionary understanding of evolution and functional biology. As the field has expanded beyond the limited number of model organisms our appreciation of evolutionary innovation and unique biology has widened as well. With this in mind, we have surveyed the hemolymph of several non-model species of Drosophila. Here we identify and describe a novel hemocyte, type-II nematocytes, found in larval stages of numerous Drosophila species. Examined in detail in Drosophila falleni and Drosophila phalerata, we find that these remarkable cells are distinct from previously described hemocytes due to their anucleate state (lacking a nucleus) and unusual morphology. Type-II nematocytes are long, narrow cells with spindle-like projections extending from a cell body with high densities of mitochondria and microtubules, and exhibit the ability to synthesize proteins. These properties are unexpected for enucleated cells, and together with our additional characterization, we demonstrate that these type-II nematocytes represent a biological novelty. Surprisingly, despite the absence of a nucleus, we observe through live cell imaging that these cells remain motile with a highly dynamic cellular shape. Furthermore, these cells demonstrate the ability to form multicellular structures, which we suggest may be a component of the innate immune response to macro-parasites. In addition, live cell imaging points to a large nucleated hemocyte, type-I nematocyte, as the progenitor cell, leading to enucleation through a budding or asymmetrical division process rather than nuclear ejection: This study is the first to report such a process of enucleation. Here we describe these cells in detail for the first time and examine their evolutionary history in Drosophila.}, } @article {pmid29134064, year = {2017}, author = {Bertolaso, M and Dieli, AM}, title = {Cancer and intercellular cooperation.}, journal = {Royal Society open science}, volume = {4}, number = {10}, pages = {170470}, pmid = {29134064}, issn = {2054-5703}, abstract = {The major transitions approach in evolutionary biology has shown that the intercellular cooperation that characterizes multicellular organisms would never have emerged without some kind of multilevel selection. Relying on this view, the Evolutionary Somatic view of cancer considers cancer as a breakdown of intercellular cooperation and as a loss of the balance between selection processes that take place at different levels of organization (particularly single cell and individual organism). This seems an elegant unifying framework for healthy organism, carcinogenesis, tumour proliferation, metastasis and other phenomena such as ageing. However, the gene-centric version of Darwinian evolution, which is often adopted in cancer research, runs into empirical problems: proto-tumoural and tumoural features in precancerous cells that would undergo 'natural selection' have proved hard to demonstrate; cells are radically context-dependent, and some stages of cancer are poorly related to genetic change. Recent perspectives propose that breakdown of intercellular cooperation could depend on 'fields' and other higher-level phenomena, and could be even mutations independent. Indeed, the field would be the context, allowing (or preventing) genetic mutations to undergo an intra-organism process analogous to natural selection. The complexities surrounding somatic evolution call for integration between multiple incomplete frameworks for interpreting intercellular cooperation and its pathologies.}, } @article {pmid29133885, year = {2017}, author = {Yu, YN and Cooper, E and Velicer, GJ}, title = {A conserved stem of the Myxococcus xanthus sRNA Pxr controls sRNA accumulation and multicellular development.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {15411}, pmid = {29133885}, issn = {2045-2322}, support = {R01 GM079690/GM/NIGMS NIH HHS/United States ; }, mesh = {Enhancer Elements, Genetic/*genetics ; Evolution, Molecular ; Genes, Bacterial/genetics ; Myxococcus xanthus/*physiology ; *Nucleic Acid Conformation ; RNA, Bacterial/chemistry/*genetics/metabolism ; Transcription, Genetic/*genetics ; }, abstract = {The small RNA (sRNA) Pxr negatively controls multicellular fruiting body formation in the bacterium Myxococcus xanthus, inhibiting the transition from growth to development when nutrients are abundant. Like many other prokaryotic sRNAs, Pxr is predicted to fold into three stem loops (SL1-SL3). SL1 and SL2 are highly conserved across the myxobacteria, whereas SL3 is much more variable. SL1 is necessary for the regulatory function of Pxr but the importance of SL3 in this regard is unknown. To test for cis genetic elements required for Pxr function, we deleted the entire pxr gene from a developmentally defective strain that fails to remove Pxr-mediated blockage of development and reintroduced variably truncated fragments of the pxr region to test for their ability to block development. These truncations demonstrated that SL3 is necessary for Pxr function in the defective strain. We further show that a highly conserved eight-base-pair segment of SL3 is not only necessary for Pxr to block development in the defective strain under starvation conditions, but is also required for Pxr to prevent fruiting body development by a developmentally proficient wild-type strain under high-nutrient conditions. This conserved segment of SL3 is also necessary for detectable levels of Pxr to accumulate, suggesting that this segment either stabilizes Pxr against premature degradation during vegetative growth or positively regulates its transcription.}, } @article {pmid29133828, year = {2017}, author = {Schenkelaars, Q and Pratlong, M and Kodjabachian, L and Fierro-Constain, L and Vacelet, J and Le Bivic, A and Renard, E and Borchiellini, C}, title = {Animal multicellularity and polarity without Wnt signaling.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {15383}, pmid = {29133828}, issn = {2045-2322}, mesh = {Animals ; *Models, Biological ; Morphogenesis/*physiology ; *Porifera/cytology/physiology ; Transforming Growth Factor beta/*metabolism ; Wnt Proteins/metabolism ; *Wnt Signaling Pathway ; }, abstract = {Acquisition of multicellularity is a central event in the evolution of Eukaryota. Strikingly, animal multicellularity coincides with the emergence of three intercellular communication pathways - Notch, TGF-β and Wnt - all considered as hallmarks of metazoan development. By investigating Oopsacas minuta and Aphrocallistes vastus, we show here that the emergence of a syncytium and plugged junctions in glass sponges coincides with the loss of essential components of the Wnt signaling (i.e. Wntless, Wnt ligands and Disheveled), whereas core components of the TGF-β and Notch modules appear unaffected. This suggests that Wnt signaling is not essential for cell differentiation, polarity and morphogenesis in glass sponges. Beyond providing a comparative study of key developmental toolkits, we define here the first case of a metazoan phylum that maintained a level of complexity similar to its relatives despite molecular degeneration of Wnt pathways.}, } @article {pmid29133443, year = {2017}, author = {Kempes, CP and Wolpert, D and Cohen, Z and Pérez-Mercader, J}, title = {The thermodynamic efficiency of computations made in cells across the range of life.}, journal = {Philosophical transactions. Series A, Mathematical, physical, and engineering sciences}, volume = {375}, number = {2109}, pages = {}, pmid = {29133443}, issn = {1471-2962}, mesh = {Biological Evolution ; Cells/*metabolism ; *Life ; Protein Biosynthesis ; Thermodynamics ; }, abstract = {Biological organisms must perform computation as they grow, reproduce and evolve. Moreover, ever since Landauer's bound was proposed, it has been known that all computation has some thermodynamic cost-and that the same computation can be achieved with greater or smaller thermodynamic cost depending on how it is implemented. Accordingly an important issue concerning the evolution of life is assessing the thermodynamic efficiency of the computations performed by organisms. This issue is interesting both from the perspective of how close life has come to maximally efficient computation (presumably under the pressure of natural selection), and from the practical perspective of what efficiencies we might hope that engineered biological computers might achieve, especially in comparison with current computational systems. Here we show that the computational efficiency of translation, defined as free energy expended per amino acid operation, outperforms the best supercomputers by several orders of magnitude, and is only about an order of magnitude worse than the Landauer bound. However, this efficiency depends strongly on the size and architecture of the cell in question. In particular, we show that the useful efficiency of an amino acid operation, defined as the bulk energy per amino acid polymerization, decreases for increasing bacterial size and converges to the polymerization cost of the ribosome. This cost of the largest bacteria does not change in cells as we progress through the major evolutionary shifts to both single- and multicellular eukaryotes. However, the rates of total computation per unit mass are non-monotonic in bacteria with increasing cell size, and also change across different biological architectures, including the shift from unicellular to multicellular eukaryotes.This article is part of the themed issue 'Reconceptualizing the origins of life'.}, } @article {pmid29133442, year = {2017}, author = {Marshall, SM and Murray, ARG and Cronin, L}, title = {A probabilistic framework for identifying biosignatures using Pathway Complexity.}, journal = {Philosophical transactions. Series A, Mathematical, physical, and engineering sciences}, volume = {375}, number = {2109}, pages = {}, pmid = {29133442}, issn = {1471-2962}, mesh = {*Biology ; Life ; Probability ; }, abstract = {One thing that discriminates living things from inanimate matter is their ability to generate similarly complex or non-random structures in a large abundance. From DNA sequences to folded protein structures, living cells, microbial communities and multicellular structures, the material configurations in biology can easily be distinguished from non-living material assemblies. Many complex artefacts, from ordinary bioproducts to human tools, though they are not living things, are ultimately produced by biological processes-whether those processes occur at the scale of cells or societies, they are the consequences of living systems. While these objects are not living, they cannot randomly form, as they are the product of a biological organism and hence are either technological or cultural biosignatures. A generalized approach that aims to evaluate complex objects as possible biosignatures could be useful to explore the cosmos for new life forms. However, it is not obvious how it might be possible to create such a self-contained approach. This would require us to prove rigorously that a given artefact is too complex to have formed by chance. In this paper, we present a new type of complexity measure, which we call 'Pathway Complexity', that allows us not only to threshold the abiotic-biotic divide, but also to demonstrate a probabilistic approach based on object abundance and complexity which can be used to unambiguously assign complex objects as biosignatures. We hope that this approach will not only open up the search for biosignatures beyond the Earth, but also allow us to explore the Earth for new types of biology, and to determine when a complex chemical system discovered in the laboratory could be considered alive.This article is part of the themed issue 'Reconceptualizing the origins of life'.}, } @article {pmid29129605, year = {2018}, author = {Pogozheva, ID and Lomize, AL}, title = {Evolution and adaptation of single-pass transmembrane proteins.}, journal = {Biochimica et biophysica acta. Biomembranes}, volume = {1860}, number = {2}, pages = {364-377}, doi = {10.1016/j.bbamem.2017.11.002}, pmid = {29129605}, issn = {0005-2736}, mesh = {*Adaptation, Physiological ; Arabidopsis/genetics/metabolism ; Cell Membrane/*metabolism ; Databases, Protein ; Dictyostelium/genetics/metabolism ; Escherichia coli/genetics/metabolism ; *Evolution, Molecular ; Humans ; Membrane Proteins/chemistry/genetics/*metabolism ; Methanocaldococcus/genetics/metabolism ; Protein Conformation, alpha-Helical ; Protein Multimerization ; Proteome/chemistry/genetics/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Species Specificity ; }, abstract = {A comparative analysis of 6039 single-pass (bitopic) membrane proteins from six evolutionarily distant organisms was performed based on data from the Membranome database. The observed repertoire of bitopic proteins is significantly enlarged in eukaryotic cells and especially in multicellular organisms due to the diversification of enzymes, emergence of proteins involved in vesicular trafficking, and expansion of receptors, structural, and adhesion proteins. The majority of bitopic proteins in multicellular organisms are located in the plasma membrane (PM) and involved in cell communication. Bitopic proteins from different membranes significantly diverge in terms of their biological functions, size, topology, domain architecture, physical properties of transmembrane (TM) helices and propensity to form homodimers. Most proteins from eukaryotic PM and endoplasmic reticulum (ER) have the N-out topology. The predicted lengths of TM helices and hydrophobic thicknesses, stabilities and hydrophobicities of TM α-helices are the highest for proteins from eukaryotic PM, intermediate for proteins from prokaryotic cells, ER and Golgi apparatus, and lowest for proteins from mitochondria, chloroplasts, and peroxisomes. Tyr and Phe residues accumulate at the cytoplasmic leaflet of PM and at the outer leaflet of membranes of bacteria, Golgi apparatus, and nucleus. The propensity for dimerization increases from unicellular to multicellular eukaryotes, from enzymes to receptors, and from intracellular membrane proteins to PM proteins. More than half of PM proteins form homodimers with a 2:1 ratio of right-handed to left-handed helix packing arrangements. The inverse ratio (1:2) was observed for dimers from the ER, Golgi and vesicles.}, } @article {pmid29128405, year = {2018}, author = {Soni, B and Saha, B and Singh, S}, title = {Systems cues governing IL6 signaling in leishmaniasis.}, journal = {Cytokine}, volume = {106}, number = {}, pages = {169-175}, doi = {10.1016/j.cyto.2017.11.001}, pmid = {29128405}, issn = {1096-0023}, mesh = {Animals ; Computer Simulation ; Interleukin-6/*metabolism ; Leishmaniasis/*metabolism ; Mice ; Models, Biological ; Phylogeny ; Principal Component Analysis ; *Signal Transduction ; *Systems Biology ; Toll-Like Receptors/metabolism ; }, abstract = {IL-6 has been proposed to favor the development of Th2 responses and play an important role in the communication between cells of multicellular organisms. They are involved in the regulation of complex cellular processes such as proliferation, differentiation and act as key player during inflammation and immune response. Th2 cytokines play an immunoregulatory role in early infection. Literature says in mice infected with L. major, IL-6 may promote the development of both Th1 and Th2 responses. IL-4 is also considered to be the signature cytokine of Th-2 response. IL-10 was initially characterized as a Th2 cytokine but later on it was proved to be a pleiotropic cytokine, secreted from different cell types including the macrophages. A major challenge is to understand how these complex non-linear processes are connected and regulated. Systems biology approaches may be used to tackle this challenge in an iterative process of quantitative mathematical analysis. In this study, we created an in silico model of IL6 mediated macrophage activation which suffers from an excessive impact of the negative feedback loop involving SOCS3. The strategy adopted in this framework may help to reduce the complexity of the leishmanial IL6 model analysis and also laydown various physiological or pathological conditions of IL6 signaling in future.}, } @article {pmid29121339, year = {2017}, author = {Polychronopoulos, D and King, JWD and Nash, AJ and Tan, G and Lenhard, B}, title = {Conserved non-coding elements: developmental gene regulation meets genome organization.}, journal = {Nucleic acids research}, volume = {45}, number = {22}, pages = {12611-12624}, pmid = {29121339}, issn = {1362-4962}, support = {MC_UP_1102/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Base Sequence ; Conserved Sequence/*genetics ; Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Genes, Developmental/genetics ; Genome/*genetics ; Humans ; Regulatory Sequences, Nucleic Acid/*genetics ; Sequence Homology, Nucleic Acid ; }, abstract = {Comparative genomics has revealed a class of non-protein-coding genomic sequences that display an extraordinary degree of conservation between two or more organisms, regularly exceeding that found within protein-coding exons. These elements, collectively referred to as conserved non-coding elements (CNEs), are non-randomly distributed across chromosomes and tend to cluster in the vicinity of genes with regulatory roles in multicellular development and differentiation. CNEs are organized into functional ensembles called genomic regulatory blocks-dense clusters of elements that collectively coordinate the expression of shared target genes, and whose span in many cases coincides with topologically associated domains. CNEs display sequence properties that set them apart from other sequences under constraint, and have recently been proposed as useful markers for the reconstruction of the evolutionary history of organisms. Disruption of several of these elements is known to contribute to diseases linked with development, and cancer. The emergence, evolutionary dynamics and functions of CNEs still remain poorly understood, and new approaches are required to enable comprehensive CNE identification and characterization. Here, we review current knowledge and identify challenges that need to be tackled to resolve the impasse in understanding extreme non-coding conservation.}, } @article {pmid29120392, year = {2017}, author = {Drezen, JM and Josse, T and Bézier, A and Gauthier, J and Huguet, E and Herniou, EA}, title = {Impact of Lateral Transfers on the Genomes of Lepidoptera.}, journal = {Genes}, volume = {8}, number = {11}, pages = {}, pmid = {29120392}, issn = {2073-4425}, abstract = {Transfer of DNA sequences between species regardless of their evolutionary distance is very common in bacteria, but evidence that horizontal gene transfer (HGT) also occurs in multicellular organisms has been accumulating in the past few years. The actual extent of this phenomenon is underestimated due to frequent sequence filtering of "alien" DNA before genome assembly. However, recent studies based on genome sequencing have revealed, and experimentally verified, the presence of foreign DNA sequences in the genetic material of several species of Lepidoptera. Large DNA viruses, such as baculoviruses and the symbiotic viruses of parasitic wasps (bracoviruses), have the potential to mediate these transfers in Lepidoptera. In particular, using ultra-deep sequencing, newly integrated transposons have been identified within baculovirus genomes. Bacterial genes have also been acquired by genomes of Lepidoptera, as in other insects and nematodes. In addition, insertions of bracovirus sequences were present in the genomes of certain moth and butterfly lineages, that were likely corresponding to rearrangements of ancient integrations. The viral genes present in these sequences, sometimes of hymenopteran origin, have been co-opted by lepidopteran species to confer some protection against pathogens.}, } @article {pmid29119267, year = {2018}, author = {Li, L and Aslam, M and Rabbi, F and Vanderwel, MC and Ashton, NW and Suh, DY}, title = {PpORS, an ancient type III polyketide synthase, is required for integrity of leaf cuticle and resistance to dehydration in the moss, Physcomitrella patens.}, journal = {Planta}, volume = {247}, number = {2}, pages = {527-541}, pmid = {29119267}, issn = {1432-2048}, support = {262038-2013//Natural Sciences and Engineering Research Council of Canada/ ; 2982-2008//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Acyltransferases/genetics/*metabolism ; Biological Evolution ; Bryopsida/*enzymology/genetics/physiology ; Dehydration ; Gene Knockout Techniques ; Mutation ; Phenotype ; Phylogeny ; Plant Leaves/enzymology/genetics/physiology ; Plant Proteins/genetics/metabolism ; Water/physiology ; }, abstract = {PpORS knockout mutants produced abnormal leaves with increased dye permeability and were more susceptible to dehydration, consistent with PpORS products being constituents of a cuticular structure in the moss. Type III polyketide synthases (PKSs) have co-evolved with terrestrial plants such that each taxon can generate a characteristic collection of polyketides, fine-tuned to its needs. 2'-Oxoalkylresorcinol synthase from Physcomitrella patens (PpORS) is basal to all plant type III PKSs in phylogenetic trees and may closely resemble their most recent common ancestor. To gain insight into the roles that ancestral plant type III PKSs might have played during early land plant evolution, we constructed and phenotypically characterized targeted knockouts of PpORS. Ors gametophores, unless submerged in water while they were developing, displayed various leaf malformations that included grossly misshapen leaves, missing or abnormal midribs, multicellular protuberances and localized necrosis. Ors leaves, particularly abnormal ones, showed increased permeability to the hydrophilic dye, toluidine blue. Ors gametophores lost water faster and were more susceptible to dehydration than those of the control strain. Our findings are consistent with ors leaves possessing a partially defective cuticle and implicate PpORS in synthesis of the intact cuticle. PpORS orthologs are present in a few moss species but have not been found in other plants. However, conceivably an ancestral ORS in early land plants may have contributed to their protection from dehydration.}, } @article {pmid29118134, year = {2017}, author = {Berger, D and Stångberg, J and Grieshop, K and Martinossi-Allibert, I and Arnqvist, G}, title = {Temperature effects on life-history trade-offs, germline maintenance and mutation rate under simulated climate warming.}, journal = {Proceedings. Biological sciences}, volume = {284}, number = {1866}, pages = {}, pmid = {29118134}, issn = {1471-2954}, mesh = {Acclimatization ; Animals ; Climate Change ; Coleoptera/*physiology ; Female ; *Germ-Line Mutation ; *Life History Traits ; Longevity ; Male ; *Mutation Rate ; Reproduction ; }, abstract = {Mutation has a fundamental influence over evolutionary processes, but how evolutionary processes shape mutation rate remains less clear. In asexual unicellular organism, increased mutation rates have been observed in stressful environments and the reigning paradigm ascribes this increase to selection for evolvability. However, this explanation does not apply in sexually reproducing species, where little is known about how the environment affects mutation rate. Here we challenged experimental lines of seed beetle, evolved at ancestral temperature or under simulated climate warming, to repair induced mutations at ancestral and stressful temperature. Results show that temperature stress causes individuals to pass on a greater mutation load to their grand-offspring. This suggests that stress-induced mutation rates, in unicellular and multicellular organisms alike, can result from compromised germline DNA repair in low condition individuals. Moreover, lines adapted to simulated climate warming had evolved increased longevity at the cost of reproduction, and this allocation decision improved germline repair. These results suggest that mutation rates can be modulated by resource allocation trade-offs encompassing life-history traits and the germline and have important implications for rates of adaptation and extinction as well as our understanding of genetic diversity in multicellular organisms.}, } @article {pmid29114025, year = {2017}, author = {Hajjar, C and Cherrier, MV and Dias Mirandela, G and Petit-Hartlein, I and Stasia, MJ and Fontecilla-Camps, JC and Fieschi, F and Dupuy, J}, title = {The NOX Family of Proteins Is Also Present in Bacteria.}, journal = {mBio}, volume = {8}, number = {6}, pages = {}, pmid = {29114025}, issn = {2150-7511}, mesh = {Algorithms ; Bacterial Proteins/chemistry/*genetics/isolation & purification/*metabolism ; Databases, Genetic ; Electron Transport ; Humans ; NADPH Oxidase 2/chemistry/genetics ; NADPH Oxidases/chemistry/*genetics/isolation & purification/*metabolism ; Oxidation-Reduction ; Oxidative Stress ; Phagocytes/enzymology ; Phylogeny ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Streptococcus pneumoniae/enzymology/*genetics ; }, abstract = {Transmembrane NADPH oxidase (NOX) enzymes have been so far only characterized in eukaryotes. In most of these organisms, they reduce molecular oxygen to superoxide and, depending on the presence of additional domains, are called NOX or dual oxidases (DUOX). Reactive oxygen species (ROS), including superoxide, have been traditionally considered accidental toxic by-products of aerobic metabolism. However, during the last decade it has become evident that both O2[•-] and H2O2 are key players in complex signaling networks and defense. A well-studied example is the production of O2[•-] during the bactericidal respiratory burst of phagocytes; this production is catalyzed by NOX2. Here, we devised and applied a novel algorithm to search for additional NOX genes in genomic databases. This procedure allowed us to discover approximately 23% new sequences from bacteria (in relation to the number of NOX-related sequences identified by the authors) that we have added to the existing eukaryotic NOX family and have used to build an expanded phylogenetic tree. We cloned and overexpressed the identified nox gene from Streptococcus pneumoniae and confirmed that it codes for an NADPH oxidase. The membrane of the S. pneumoniae NOX protein (SpNOX) shares many properties with its eukaryotic counterparts, such as affinity for NADPH and flavin adenine dinucleotide, superoxide dismutase and diphenylene iodonium inhibition, cyanide resistance, oxygen consumption, and superoxide production. Traditionally, NOX enzymes in eukaryotes are related to functions linked to multicellularity. Thus, the discovery of a large family of NOX-related enzymes in the bacterial world brings up fascinating questions regarding their role in this new biological context.IMPORTANCE NADPH oxidase (NOX) enzymes have not yet been reported in bacteria. Here, we carried out computational and experimental studies to provide the first characterization of a prokaryotic NOX. Out of 996 prokaryotic proteins showing NOX signatures, we initially selected, cloned, and overexpressed four of them. Subsequently, and based on preliminary testing, we concentrated our efforts on Streptococcus SpNOX, which shares many biochemical characteristics with NOX2, the referent model of NOX enzymes. Our work makes possible, for the first time, the study of pure forms of this important family of enzymes, allowing for biophysical and molecular characterization in an unprecedented way. Similar advances regarding other membrane protein families have led to new structures, further mechanistic studies, and the improvement of inhibitors. In addition, biological functions of these newly described bacterial enzymes will be certainly discovered in the near future.}, } @article {pmid29112727, year = {2018}, author = {Higo, A and Isu, A and Fukaya, Y and Ehira, S and Hisabori, T}, title = {Application of CRISPR Interference for Metabolic Engineering of the Heterocyst-Forming Multicellular Cyanobacterium Anabaena sp. PCC 7120.}, journal = {Plant & cell physiology}, volume = {59}, number = {1}, pages = {119-127}, doi = {10.1093/pcp/pcx166}, pmid = {29112727}, issn = {1471-9053}, mesh = {Anabaena/*genetics/metabolism ; Bacterial Proteins/genetics/metabolism ; Blotting, Western ; *CRISPR-Cas Systems ; *Gene Expression Regulation, Bacterial ; Glutamate-Ammonia Ligase/genetics/metabolism ; Metabolic Engineering/*methods ; Models, Genetic ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Anabaena sp. PCC 7120 (A. 7120) is a heterocyst-forming multicellular cyanobacterium that performs nitrogen fixation. This cyanobacterium has been extensively studied as a model for multicellularity in prokaryotic cells. We have been interested in photosynthetic production of nitrogenous compounds using A. 7120. However, the lack of efficient gene repression tools has limited its usefulness. We originally developed an artificial endogenous gene repression method in this cyanobacterium using small antisense RNA. However, the narrow dynamic range of repression of this method needs to be improved. Recently, clustered regularly interspaced short palindromic repeat (CRISPR) interference (CRISPRi) technology was developed and was successfully applied in some unicellular cyanobacteria. The technology requires expression of nuclease-deficient CRISPR-associated protein 9 (dCas9) and a single guide RNA (sgRNA) that is complementary to a target sequence, to repress expression of the target gene. In this study, we employed CRISPRi technology for photosynthetic production of ammonium through repression of glnA, the only gene encoding glutamine synthetase that is essential for nitrogen assimilation in A. 7120. By strictly regulating dCas9 expression using the TetR gene induction system, we succeeded in fine-tuning the GlnA protein in addition to the level of glnA transcripts. Expression of sgRNA by the heterocyst-specific nifB promoter led to efficient repression of GlnA in heterocysts, as well as in vegetative cells. Finally, we showed that ammonium is excreted into the medium only when inducers of expression of dCas9 were added. In conclusion, CRISPRi enables temporal control of desired products and will be a useful tool for basic science.}, } @article {pmid29109290, year = {2017}, author = {Brennan, JJ and Messerschmidt, JL and Williams, LM and Matthews, BJ and Reynoso, M and Gilmore, TD}, title = {Sea anemone model has a single Toll-like receptor that can function in pathogen detection, NF-κB signal transduction, and development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {47}, pages = {E10122-E10131}, pmid = {29109290}, issn = {1091-6490}, mesh = {Animals ; Cell Line ; Chickens ; Embryo, Nonmammalian ; Fibroblasts/drug effects/immunology/microbiology ; Flagellin/pharmacology ; Gene Expression Regulation, Developmental/*immunology ; HEK293 Cells ; Hot Temperature ; Humans ; Immunity, Innate ; Morpholinos/genetics/metabolism ; Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics/immunology ; Myeloid Differentiation Factor 88/genetics/immunology ; NF-kappa B/genetics/*immunology ; Protein Binding ; Sea Anemones/genetics/growth & development/*immunology/microbiology ; Signal Transduction ; Toll-Like Receptors/antagonists & inhibitors/genetics/*immunology ; Vibrio/pathogenicity/physiology ; }, abstract = {In organisms from insects to vertebrates, Toll-like receptors (TLRs) are primary pathogen detectors that activate downstream pathways, specifically those that direct expression of innate immune effector genes. TLRs also have roles in development in many species. The sea anemone Nematostella vectensis is a useful cnidarian model to study the origins of TLR signaling because its genome encodes a single TLR and homologs of many downstream signaling components, including the NF-κB pathway. We have characterized the single N. vectensis TLR (Nv-TLR) and demonstrated that it can activate canonical NF-κB signaling in human cells. Furthermore, we show that the intracellular Toll/IL-1 receptor (TIR) domain of Nv-TLR can interact with the human TLR adapter proteins MAL and MYD88. We demonstrate that the coral pathogen Vibrio coralliilyticus causes a rapidly lethal disease in N. vectensis and that heat-inactivated V. coralliilyticus and bacterial flagellin can activate a reconstituted Nv-TLR-to-NF-κB pathway in human cells. By immunostaining of anemones, we show that Nv-TLR is expressed in a subset of cnidocytes and that many of these Nv-TLR-expressing cells also express Nv-NF-κB. Additionally, the nematosome, which is a Nematostella-specific multicellular structure, expresses Nv-TLR and many innate immune pathway homologs and can engulf V. coralliilyticus Morpholino knockdown indicates that Nv-TLR also has an essential role during early embryonic development. Our characterization of this primitive TLR and identification of a bacterial pathogen for N. vectensis reveal ancient TLR functions and provide a model for studying the molecular basis of cnidarian disease and immunity.}, } @article {pmid29109232, year = {2017}, author = {Stapley, J and Feulner, PGD and Johnston, SE and Santure, AW and Smadja, CM}, title = {Recombination: the good, the bad and the variable.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1736}, pages = {}, pmid = {29109232}, issn = {1471-2970}, mesh = {Genome ; Recombination, Genetic/genetics/*physiology ; Reproduction ; }, abstract = {Recombination, the process by which DNA strands are broken and repaired, producing new combinations of alleles, occurs in nearly all multicellular organisms and has important implications for many evolutionary processes. The effects of recombination can be good, as it can facilitate adaptation, but also bad when it breaks apart beneficial combinations of alleles, and recombination is highly variable between taxa, species, individuals and across the genome. Understanding how and why recombination rate varies is a major challenge in biology. Most theoretical and empirical work has been devoted to understanding the role of recombination in the evolution of sex-comparing between sexual and asexual species or populations. How recombination rate evolves and what impact this has on evolutionary processes within sexually reproducing organisms has received much less attention. This Theme Issue focusses on how and why recombination rate varies in sexual species, and aims to coalesce knowledge of the molecular mechanisms governing recombination with our understanding of the evolutionary processes driving variation in recombination within and between species. By integrating these fields, we can identify important knowledge gaps and areas for future research, and pave the way for a more comprehensive understanding of how and why recombination rate varies.}, } @article {pmid29109219, year = {2017}, author = {Stapley, J and Feulner, PGD and Johnston, SE and Santure, AW and Smadja, CM}, title = {Variation in recombination frequency and distribution across eukaryotes: patterns and processes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1736}, pages = {}, pmid = {29109219}, issn = {1471-2970}, mesh = {Chromosome Mapping ; Eukaryota/*genetics ; *Genetic Linkage ; *Genome ; Recombination, Genetic/*genetics ; }, abstract = {Recombination, the exchange of DNA between maternal and paternal chromosomes during meiosis, is an essential feature of sexual reproduction in nearly all multicellular organisms. While the role of recombination in the evolution of sex has received theoretical and empirical attention, less is known about how recombination rate itself evolves and what influence this has on evolutionary processes within sexually reproducing organisms. Here, we explore the patterns of, and processes governing recombination in eukaryotes. We summarize patterns of variation, integrating current knowledge with an analysis of linkage map data in 353 organisms. We then discuss proximate and ultimate processes governing recombination rate variation and consider how these influence evolutionary processes. Genome-wide recombination rates (cM/Mb) can vary more than tenfold across eukaryotes, and there is large variation in the distribution of recombination events across closely related taxa, populations and individuals. We discuss how variation in rate and distribution relates to genome architecture, genetic and epigenetic mechanisms, sex, environmental perturbations and variable selective pressures. There has been great progress in determining the molecular mechanisms governing recombination, and with the continued development of new modelling and empirical approaches, there is now also great opportunity to further our understanding of how and why recombination rate varies.This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'.}, } @article {pmid29104545, year = {2017}, author = {Dobson, GP and Arsyad, A and Letson, HL}, title = {The Adenosine Hypothesis Revisited: Modulation of Coupling between Myocardial Perfusion and Arterial Compliance.}, journal = {Frontiers in physiology}, volume = {8}, number = {}, pages = {824}, pmid = {29104545}, issn = {1664-042X}, abstract = {For over four decades the thoracic aortic ring model has become one of the most widely used methods to study vascular reactivity and electromechanical coupling. A question that is rarely asked, however, is what function does a drug-mediated relaxation (or contraction) in this model serve in the intact system? The physiological significance of adenosine relaxation in rings isolated from large elastic conduit arteries from a wide range of species remains largely unknown. We propose that adenosine relaxation increases aortic compliance in acute stress states and facilitates ventricular-arterial (VA) coupling, and thereby links compliance and coronary artery perfusion to myocardial energy metabolism. In 1963 Berne argued that adenosine acts as a local negative feedback regulator between oxygen supply and demand in the heart during hypoxic/ischemic stress. The adenosine VA coupling hypothesis extends and enhances Berne's "adenosine hypothesis" from a local regulatory scheme in the heart to include conduit arterial function. In multicellular organisms, evolution may have selected adenosine, nitric oxide, and other vascular mediators, to modulate VA coupling for optimal transfer of oxygen (and nutrients) from the lung, heart, large conduit arteries, arterioles and capillaries to respiring mitochondria. Finally, a discussion of the potential clinical significance of adenosine modulation of VA coupling is extended to vascular aging and disease, including hypertension, diabetes, obesity, coronary artery disease and heart failure.}, } @article {pmid29101312, year = {2017}, author = {Björnfot Holmström, S and Clark, R and Zwicker, S and Bureik, D and Kvedaraite, E and Bernasconi, E and Nguyen Hoang, AT and Johannsen, G and Marsland, BJ and Boström, EA and Svensson, M}, title = {Gingival Tissue Inflammation Promotes Increased Matrix Metalloproteinase-12 Production by CD200R[low] Monocyte-Derived Cells in Periodontitis.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {199}, number = {12}, pages = {4023-4035}, doi = {10.4049/jimmunol.1700672}, pmid = {29101312}, issn = {1550-6606}, mesh = {Adult ; Antigens, Surface/biosynthesis/genetics/*physiology ; Cell Division ; Cells, Cultured ; Coculture Techniques ; Cyclooxygenase Inhibitors/pharmacology ; Epithelial Cells/metabolism ; Fibroblasts/metabolism ; Flow Cytometry ; Gene Expression Regulation ; Gingiva/*enzymology/pathology ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Inflammation ; Keratinocytes/metabolism ; Matrix Metalloproteinase 12/biosynthesis/genetics/*physiology ; Monocytes/*enzymology/pathology ; Orexin Receptors ; Periodontitis/*enzymology/pathology ; Pyrazoles/pharmacology ; Real-Time Polymerase Chain Reaction ; Receptors, Cell Surface/biosynthesis/genetics/*physiology ; }, abstract = {Irreversible tissue recession in chronic inflammatory diseases is associated with dysregulated immune activation and production of tissue degradative enzymes. In this study, we identified elevated levels of matrix metalloproteinase (MMP)-12 in gingival tissue of patients with the chronic inflammatory disease periodontitis (PD). The source of MMP12 was cells of monocyte origin as determined by the expression of CD14, CD68, and CD64. These MMP12-producing cells showed reduced surface levels of the coinhibitory molecule CD200R. Similarly, establishing a multicellular three-dimensional model of human oral mucosa with induced inflammation promoted MMP12 production and reduced CD200R surface expression by monocyte-derived cells. MMP12 production by monocyte-derived cells was induced by CSF2 rather than the cyclooxygenase-2 pathway, and treatment of monocyte-derived cells with a CD200R ligand reduced CSF2-induced MMP12 production. Further, MMP12-mediated degradation of the extracellular matrix proteins tropoelastin and fibronectin in the tissue model coincided with a loss of Ki-67, a protein strictly associated with cell proliferation. Reduced amounts of tropoelastin were confirmed in gingival tissue from PD patients. Thus, this novel association of the CD200/CD200R pathway with MMP12 production by monocyte-derived cells may play a key role in PD progression and will be important to take into consideration in the development of future strategies to diagnose, treat, and prevent PD.}, } @article {pmid29099481, year = {2018}, author = {Strasser, A and Vaux, DL}, title = {Viewing BCL2 and cell death control from an evolutionary perspective.}, journal = {Cell death and differentiation}, volume = {25}, number = {1}, pages = {13-20}, pmid = {29099481}, issn = {1476-5403}, mesh = {Animals ; *Apoptosis ; Biological Evolution ; Caenorhabditis elegans/genetics ; Humans ; Inflammation ; Neoplasms/drug therapy ; Proto-Oncogene Proteins c-bcl-2/genetics/*physiology ; Stress, Physiological ; }, abstract = {The last 30 years of studying BCL2 have brought cell death research into the molecular era, and revealed its relevance to human pathophysiology. Most, if not all metazoans use an evolutionarily conserved process for cellular self destruction that is controlled and implemented by proteins related to BCL2. We propose the anti-apoptotic BCL2-like and pro-apoptotic BH3-only members of the family arose through duplication and modification of genes for the pro-apoptotic multi-BH domain family members, such as BAX and BAK1. In that way, a cell suicide process that initially evolved as a mechanism for defense against intracellular parasites was then also used in multicellular organisms for morphogenesis and to maintain the correct number of cells in adults by balancing cell production by mitosis.}, } @article {pmid29088489, year = {2018}, author = {Higo, A and Isu, A and Fukaya, Y and Hisabori, T}, title = {Spatio-Temporal Gene Induction Systems in the Heterocyst-Forming Multicellular Cyanobacterium Anabaena sp. PCC 7120.}, journal = {Plant & cell physiology}, volume = {59}, number = {1}, pages = {82-89}, doi = {10.1093/pcp/pcx163}, pmid = {29088489}, issn = {1471-9053}, mesh = {Adenine/pharmacology ; Anabaena/cytology/*genetics ; Bacterial Proteins/*genetics/metabolism ; Gene Expression Regulation, Bacterial/drug effects/*genetics ; Models, Genetic ; Nitrogen/metabolism ; Nitrogen Fixation/*genetics ; Promoter Regions, Genetic/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Riboswitch/genetics ; Theophylline/pharmacology ; }, abstract = {In the last decade, much progress has been made in the photosynthetic production of valuable products using unicellular cyanobacteria. However, production of some products requires dark, anaerobic incubation, which prevents practical applications using these organisms. Anabaena sp. PCC 7120 (A. 7120) is a heterocyst-forming multicellular cyanobacterium that is easy to manipulate genetically. Upon nitrogen step-down, this strain differentiates heterocysts that retain micro-oxic conditions for nitrogen fixation. We have developed gene regulation tools in this cyanobacterium. However, lack of a cell type-specific gene induction system has prevented A. 7120 from becoming a bona fide attractive host for photosynthetic production. We validated the usability of two transcriptional ON riboswitches that respond to theophylline or adenine. We then created a cell type-specific gene induction system by combining the riboswitches and promoters specific to either heterocysts or vegetative cells. We also created another cell type-specific gene induction system using small RNA that activates translation. Consequently, our study has expanded the toolbox for gene regulation in cyanobacteria and has enabled spatio-temporal gene induction in multicellular cyanobacteria.}, } @article {pmid29085064, year = {2017}, author = {Sipos, G and Prasanna, AN and Walter, MC and O'Connor, E and Bálint, B and Krizsán, K and Kiss, B and Hess, J and Varga, T and Slot, J and Riley, R and Bóka, B and Rigling, D and Barry, K and Lee, J and Mihaltcheva, S and LaButti, K and Lipzen, A and Waldron, R and Moloney, NM and Sperisen, C and Kredics, L and Vágvölgyi, C and Patrignani, A and Fitzpatrick, D and Nagy, I and Doyle, S and Anderson, JB and Grigoriev, IV and Güldener, U and Münsterkötter, M and Nagy, LG}, title = {Genome expansion and lineage-specific genetic innovations in the forest pathogenic fungi Armillaria.}, journal = {Nature ecology & evolution}, volume = {1}, number = {12}, pages = {1931-1941}, doi = {10.1038/s41559-017-0347-8}, pmid = {29085064}, issn = {2397-334X}, mesh = {Armillaria/*genetics ; Fungal Proteins/*genetics ; *Genome, Fungal ; Proteomics ; Sequence Analysis, RNA ; Species Specificity ; Transcriptome ; }, abstract = {Armillaria species are both devastating forest pathogens and some of the largest terrestrial organisms on Earth. They forage for hosts and achieve immense colony sizes via rhizomorphs, root-like multicellular structures of clonal dispersal. Here, we sequenced and analysed the genomes of four Armillaria species and performed RNA sequencing and quantitative proteomic analysis on the invasive and reproductive developmental stages of A. ostoyae. Comparison with 22 related fungi revealed a significant genome expansion in Armillaria, affecting several pathogenicity-related genes, lignocellulose-degrading enzymes and lineage-specific genes expressed during rhizomorph development. Rhizomorphs express an evolutionarily young transcriptome that shares features with the transcriptomes of both fruiting bodies and vegetative mycelia. Several genes show concomitant upregulation in rhizomorphs and fruiting bodies and share cis-regulatory signatures in their promoters, providing genetic and regulatory insights into complex multicellularity in fungi. Our results suggest that the evolution of the unique dispersal and pathogenicity mechanisms of Armillaria might have drawn upon ancestral genetic toolkits for wood-decay, morphogenesis and complex multicellularity.}, } @article {pmid29070590, year = {2017}, author = {de Wiljes, OO and van Elburg, RAJ and Keijzer, FA}, title = {Modelling the effects of short and random proto-neural elongations.}, journal = {Journal of the Royal Society, Interface}, volume = {14}, number = {135}, pages = {}, pmid = {29070590}, issn = {1742-5662}, mesh = {Animals ; Axons/*physiology ; *Computer Simulation ; Dendrites/*physiology ; *Models, Biological ; }, abstract = {To understand how neurons and nervous systems first evolved, we need an account of the origins of neural elongations: why did neural elongations (axons and dendrites) first originate, such that they could become the central component of both neurons and nervous systems? Two contrasting conceptual accounts provide different answers to this question. Braitenberg's vehicles provide the iconic illustration of the dominant input-output (IO) view. Here, the basic role of neural elongations is to connect sensors to effectors, both situated at different positions within the body. For this function, neural elongations are thought of as comparatively long and specific connections, which require an articulated body involving substantial developmental processes to build. Internal coordination (IC) models stress a different function for early nervous systems. Here, the coordination of activity across extended parts of a multicellular body is held central, in particular, for the contractions of (muscle) tissue. An IC perspective allows the hypothesis that the earliest proto-neural elongations could have been functional even when they were initially simple, short and random connections, as long as they enhanced the patterning of contractile activity across a multicellular surface. The present computational study provides a proof of concept that such short and random neural elongations can play this role. While an excitable epithelium can generate basic forms of patterning for small body configurations, adding elongations allows such patterning to scale up to larger bodies. This result supports a new, more gradual evolutionary route towards the origins of the very first neurons and nervous systems.}, } @article {pmid29069493, year = {2018}, author = {Gao, D and Chu, Y and Xia, H and Xu, C and Heyduk, K and Abernathy, B and Ozias-Akins, P and Leebens-Mack, JH and Jackson, SA}, title = {Horizontal Transfer of Non-LTR Retrotransposons from Arthropods to Flowering Plants.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {354-364}, pmid = {29069493}, issn = {1537-1719}, mesh = {Animals ; Arachis/*genetics ; Arthropods/*genetics ; Base Sequence ; *Gene Transfer, Horizontal ; Genome, Plant ; Phylogeny ; *Retroelements ; Sequence Homology, Nucleic Acid ; }, abstract = {Even though lateral movements of transposons across families and even phyla within multicellular eukaryotic kingdoms have been found, little is known about transposon transfer between the kingdoms Animalia and Plantae. We discovered a novel non-LTR retrotransposon, AdLINE3, in a wild peanut species. Sequence comparisons and phylogenetic analyses indicated that AdLINE3 is a member of the RTE clade, originally identified in a nematode and rarely reported in plants. We identified RTE elements in 82 plants, spanning angiosperms to algae, including recently active elements in some flowering plants. RTE elements in flowering plants were likely derived from a single family we refer to as An-RTE. Interestingly, An-RTEs show significant DNA sequence identity with non-LTR retroelements from 42 animals belonging to four phyla. Moreover, the sequence identity of RTEs between two arthropods and two plants was higher than that of homologous genes. Phylogenetic and evolutionary analyses of RTEs from both animals and plants suggest that the An-RTE family was likely transferred horizontally into angiosperms from an ancient aphid(s) or ancestral arthropod(s). Notably, some An-RTEs were recruited as coding sequences of functional genes participating in metabolic or other biochemical processes in plants. This is the first potential example of horizontal transfer of transposons between animals and flowering plants. Our findings help to understand exchanges of genetic material between the kingdom Animalia and Plantae and suggest arthropods likely impacted on plant genome evolution.}, } @article {pmid29065305, year = {2017}, author = {Brunet, T and King, N}, title = {The Origin of Animal Multicellularity and Cell Differentiation.}, journal = {Developmental cell}, volume = {43}, number = {2}, pages = {124-140}, pmid = {29065305}, issn = {1878-1551}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 GM089977/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation ; *Cell Lineage ; }, abstract = {Over 600 million years ago, animals evolved from a unicellular or colonial organism whose cell(s) captured bacteria with a collar complex, a flagellum surrounded by a microvillar collar. Using principles from evolutionary cell biology, we reason that the transition to multicellularity required modification of pre-existing mechanisms for extracellular matrix synthesis and cytokinesis. We discuss two hypotheses for the origin of animal cell types: division of labor from ancient plurifunctional cells and conversion of temporally alternating phenotypes into spatially juxtaposed cell types. Mechanistic studies in diverse animals and their relatives promise to deepen our understanding of animal origins and cell biology.}, } @article {pmid29061899, year = {2017}, author = {Dukas, R}, title = {Cognitive innovations and the evolutionary biology of expertise.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1735}, pages = {}, pmid = {29061899}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; *Cognition ; *Learning ; Social Learning ; }, abstract = {Animal life can be perceived as the selective use of information for maximizing survival and reproduction. All organisms including bacteria and protists rely on genetic networks to build and modulate sophisticated structures and biochemical mechanisms for perceiving information and responding to environmental changes. Animals, however, have gone through a series of innovations that dramatically increased their capacity to acquire, retain and act upon information. Multicellularity was associated with the evolution of the nervous system, which took over many tasks of internal communication and coordination. This paved the way for the evolution of learning, initially based on individual experience and later also via social interactions. The increased importance of social learning also led to the evolution of language in a single lineage. Individuals' ability to dramatically increase performance via learning may have led to an evolutionary cycle of increased lifespan and greater investment in cognitive abilities, as well as in the time necessary for the development and refinement of expertise. We still know little, however, about the evolutionary biology, genetics and neurobiological mechanisms that underlie such expertise and its development.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'.}, } @article {pmid29061894, year = {2017}, author = {Aktipis, A and Maley, CC}, title = {Cooperation and cheating as innovation: insights from cellular societies.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1735}, pages = {}, pmid = {29061894}, issn = {1471-2970}, support = {P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Cooperative Behavior ; *Eukaryota ; Microbial Interactions ; *Microbiota ; Models, Biological ; }, abstract = {The capacity to innovate is often considered a defining feature of human societies, but it is not a capacity that is unique to human societies: innovation occurs in cellular societies as well. Cellular societies such as multicellular bodies and microbial communities, including the human microbiome, are capable of innovation in response to novel opportunities and threats. Multicellularity represents a suite of innovations for cellular cooperation, but multicellularity also opened up novel opportunities for cells to cheat, exploiting the infrastructure and resources of the body. Multicellular bodies evolve less quickly than the cells within them, leaving them vulnerable to cellular innovations that can lead to cancer and infections. In order to counter these threats, multicellular bodies deploy additional innovations including the adaptive immune system and the development of partnerships with preferred microbial partners. What can we learn from examining these innovations in cooperation and cheating in cellular societies? First, innovation in social systems involves a constant tension between novel mechanisms that enable greater size and complexity of cooperative entities and novel ways of cheating. Second, cultivating cooperation with partners who can rapidly and effectively innovate (such as microbes) is important for large entities including multicellular bodies. And third, multicellularity enabled cells to manage risk socially, allowing organisms to survive in challenging environments where life would otherwise be impossible. Throughout, we ask how insights from cellular societies might be translated into new innovations in human health and medicine, promoting and protecting the cellular cooperation that makes us viable multicellular organisms.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'.}, } @article {pmid29061893, year = {2017}, author = {Ratcliff, WC and Herron, M and Conlin, PL and Libby, E}, title = {Nascent life cycles and the emergence of higher-level individuality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1735}, pages = {}, pmid = {29061893}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Individuality ; *Life Cycle Stages ; *Life History Traits ; Models, Genetic ; Mutation ; }, abstract = {Evolutionary transitions in individuality (ETIs) occur when formerly autonomous organisms evolve to become parts of a new, 'higher-level' organism. One of the first major hurdles that must be overcome during an ETI is the emergence of Darwinian evolvability in the higher-level entity (e.g. a multicellular group), and the loss of Darwinian autonomy in the lower-level units (e.g. individual cells). Here, we examine how simple higher-level life cycles are a key innovation during an ETI, allowing this transfer of fitness to occur 'for free'. Specifically, we show how novel life cycles can arise and lead to the origin of higher-level individuals by (i) mitigating conflicts between levels of selection, (ii) engendering the expression of heritable higher-level traits and (iii) allowing selection to efficiently act on these emergent higher-level traits. Further, we compute how canonical early life cycles vary in their ability to fix beneficial mutations via mathematical modelling. Life cycles that lack a persistent lower-level stage and develop clonally are far more likely to fix 'ratcheting' mutations that limit evolutionary reversion to the pre-ETI state. By stabilizing the fragile first steps of an evolutionary transition in individuality, nascent higher-level life cycles may play a crucial role in the origin of complex life.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'.}, } @article {pmid29050666, year = {2017}, author = {Fortier, LC}, title = {The Contribution of Bacteriophages to the Biology and Virulence of Pathogenic Clostridia.}, journal = {Advances in applied microbiology}, volume = {101}, number = {}, pages = {169-200}, doi = {10.1016/bs.aambs.2017.05.002}, pmid = {29050666}, issn = {0065-2164}, mesh = {Bacteriophages/*physiology ; Clostridioides difficile/pathogenicity/physiology/*virology ; Humans ; Prophages ; Virulence ; }, abstract = {Bacteriophages are key players in the evolution of most bacteria. Temperate phages have been associated with virulence of some of the deadliest pathogenic bacteria. Among the most notorious cases, the genes encoding the botulinum neurotoxin produced by Clostridium botulinum types C and D and the α-toxin (TcnA) produced by Clostridium novyi are both encoded within prophage genomes. Clostridium difficile is another important human pathogen and the recent identification of a complete binary toxin locus (CdtLoc) carried on a C. difficile prophage raises the potential for horizontal transfer of toxin genes by mobile genetic elements. Although the TcdA and TcdB toxins produced by C. difficile have never been found outside the pathogenicity locus (PaLoc), some prophages can still influence their production. Prophages can alter the expression of several metabolic and regulatory genes in C. difficile, as well as cell surface proteins such as CwpV, which confers phage resistance. Homologs of an Agr-like quorum sensing system have been identified in a C. difficile prophage, suggesting that it could possibly participate in cell-cell communication. Yet, other C. difficile prophages contain riboswitches predicted to recognize the secondary messenger molecule c-di-GMP involved in bacterial multicellular behaviors. Altogether, recent findings on clostridial phages underline the diversity of mechanisms and intricate relationship linking phages with their host. Here, milestone discoveries linking phages and virulence of some of the most pathogenic clostridial species will be retraced, with a focus on C. botulinum, C. novyi, C. difficile, and Clostridium perfringens phages, for which evidences are mostly available.}, } @article {pmid29046735, year = {2017}, author = {Luebeck, EG and Curtius, K and Hazelton, WD and Maden, S and Yu, M and Thota, PN and Patil, DT and Chak, A and Willis, JE and Grady, WM}, title = {Identification of a key role of widespread epigenetic drift in Barrett's esophagus and esophageal adenocarcinoma.}, journal = {Clinical epigenetics}, volume = {9}, number = {}, pages = {113}, pmid = {29046735}, issn = {1868-7083}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; P50 CA150964/CA/NCI NIH HHS/United States ; U01 CA086402/CA/NCI NIH HHS/United States ; U01 CA182940/CA/NCI NIH HHS/United States ; P30 DK097948/DK/NIDDK NIH HHS/United States ; P30 CA043703/CA/NCI NIH HHS/United States ; U01 CA152756/CA/NCI NIH HHS/United States ; U54 CA163060/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/*genetics ; Aged ; Barrett Esophagus/*genetics ; CpG Islands ; *DNA Methylation ; Databases, Genetic ; Disease Progression ; Epigenesis, Genetic ; Esophageal Neoplasms/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; *Genetic Drift ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Models, Genetic ; }, abstract = {BACKGROUND: Recent studies have identified age-related changes in DNA methylation patterns in normal and cancer tissues in a process that is called epigenetic drift. However, the evolving patterns, functional consequences, and dynamics of epigenetic drift during carcinogenesis remain largely unexplored. Here we analyze the evolution of epigenetic drift patterns during progression from normal squamous esophagus tissue to Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) using 173 tissue samples from 100 (nonfamilial) BE patients, along with publically available datasets including The Cancer Genome Atlas (TCGA).

RESULTS: Our analysis reveals extensive methylomic drift between normal squamous esophagus and BE tissues in nonprogressed BE patients, with differential drift affecting 4024 (24%) of 16,984 normally hypomethylated cytosine-guanine dinucleotides (CpGs) occurring in CpG islands. The majority (63%) of islands that include drift CpGs are associated with gene promoter regions. Island CpGs that drift have stronger pairwise correlations than static islands, reflecting collective drift consistent with processive DNA methylation maintenance. Individual BE tissues are extremely heterogeneous in their distribution of methylomic drift and encompass unimodal low-drift to bimodal high-drift patterns, reflective of differences in BE tissue age. Further analysis of longitudinally collected biopsy samples from 20 BE patients confirm the time-dependent evolution of these drift patterns. Drift patterns in EAC are similar to those in BE, but frequently exhibit enhanced bimodality and advanced mode drift. To better understand the observed drift patterns, we developed a multicellular stochastic model at the CpG island level. Importantly, we find that nonlinear feedback in the model between mean island methylation and CpG methylation rates is able to explain the widely heterogeneous collective drift patterns. Using matched gene expression and DNA methylation data in EAC from TCGA and other publically available data, we also find that advanced methylomic drift is correlated with significant transcriptional repression of ~ 200 genes in important regulatory and developmental pathways, including several checkpoint and tumor suppressor-like genes.

CONCLUSIONS: Taken together, our findings suggest that epigenetic drift evolution acts to significantly reduce the expression of developmental genes that may alter tissue characteristics and improve functional adaptation during BE to EAC progression.}, } @article {pmid29021161, year = {2017}, author = {Jackson, MDB and Duran-Nebreda, S and Bassel, GW}, title = {Network-based approaches to quantify multicellular development.}, journal = {Journal of the Royal Society, Interface}, volume = {14}, number = {135}, pages = {}, pmid = {29021161}, issn = {1742-5662}, support = {BB/M01116X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L010232/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N009754/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Humans ; *Models, Biological ; }, abstract = {Multicellularity and cellular cooperation confer novel functions on organs following a structure-function relationship. How regulated cell migration, division and differentiation events generate cellular arrangements has been investigated, providing insight into the regulation of genetically encoded patterning processes. Much less is known about the higher-order properties of cellular organization within organs, and how their functional coordination through global spatial relations shape and constrain organ function. Key questions to be addressed include: why are cells organized in the way they are? What is the significance of the patterns of cellular organization selected for by evolution? What other configurations are possible? These may be addressed through a combination of global cellular interaction mapping and network science to uncover the relationship between organ structure and function. Using this approach, global cellular organization can be discretized and analysed, providing a quantitative framework to explore developmental processes. Each of the local and global properties of integrated multicellular systems can be analysed and compared across different tissues and models in discrete terms. Advances in high-resolution microscopy and image analysis continue to make cellular interaction mapping possible in an increasing variety of biological systems and tissues, broadening the further potential application of this approach. Understanding the higher-order properties of complex cellular assemblies provides the opportunity to explore the evolution and constraints of cell organization, establishing structure-function relationships that can guide future organ design.}, } @article {pmid28988859, year = {2017}, author = {Vermeij, GJ}, title = {How the Land Became the Locus of Major Evolutionary Innovations.}, journal = {Current biology : CB}, volume = {27}, number = {20}, pages = {3178-3182.e1}, doi = {10.1016/j.cub.2017.08.076}, pmid = {28988859}, issn = {1879-0445}, mesh = {Animals ; *Biological Evolution ; *Embryophyta/anatomy & histology/physiology ; *Environment ; *Invertebrates/anatomy & histology/physiology ; *Vertebrates/anatomy & histology/physiology ; }, abstract = {Life originated in the sea and evolved its early metabolic pathways in water [1, 2]. Nevertheless, activities of organisms on land have influenced and enriched marine ecosystems with oxygen and nutrients for billions of years [3-7]. In contrast to the history of species diversity in the sea and on land [8-10] and the flows of resources within and between these two realms [11], little is known about the times and places of origin of major metabolic and ecological innovations during the Phanerozoic. Many innovations among multicellular organisms originated in the sea during or before the Cambrian, including predation and most of its variations, biomineralization, colonial or clonal growth, bioerosion, deposit feeding, bioturbation by animals, communication at a distance by vision and olfaction, photosymbiosis, chemosymbiosis, suspension feeding, osmotrophy, internal fertilization, jet propulsion, undulatory locomotion, and appendages for movement. Activity is less constrained in air than in the denser, more viscous medium of water [9, 12-14]. I therefore predict that high-performance metabolic and ecological innovations should predominantly originate on land after the Ordovician once organisms had conquered the challenges of life away from water and later appeared in the sea, either in marine-colonizing clades or by arising separately in clades that never left the sea. In support of this hypothesis, I show that 11 of 13 major post-Ordovician innovations appeared first or only on land. This terrestrial locus of innovation cannot be explained by the Cretaceous to recent expansion of diversity on land. It reveals one of several irreversible shifts in the history of life.}, } @article {pmid28985561, year = {2017}, author = {Bowman, JL and Kohchi, T and Yamato, KT and Jenkins, J and Shu, S and Ishizaki, K and Yamaoka, S and Nishihama, R and Nakamura, Y and Berger, F and Adam, C and Aki, SS and Althoff, F and Araki, T and Arteaga-Vazquez, MA and Balasubrmanian, S and Barry, K and Bauer, D and Boehm, CR and Briginshaw, L and Caballero-Perez, J and Catarino, B and Chen, F and Chiyoda, S and Chovatia, M and Davies, KM and Delmans, M and Demura, T and Dierschke, T and Dolan, L and Dorantes-Acosta, AE and Eklund, DM and Florent, SN and Flores-Sandoval, E and Fujiyama, A and Fukuzawa, H and Galik, B and Grimanelli, D and Grimwood, J and Grossniklaus, U and Hamada, T and Haseloff, J and Hetherington, AJ and Higo, A and Hirakawa, Y and Hundley, HN and Ikeda, Y and Inoue, K and Inoue, SI and Ishida, S and Jia, Q and Kakita, M and Kanazawa, T and Kawai, Y and Kawashima, T and Kennedy, M and Kinose, K and Kinoshita, T and Kohara, Y and Koide, E and Komatsu, K and Kopischke, S and Kubo, M and Kyozuka, J and Lagercrantz, U and Lin, SS and Lindquist, E and Lipzen, AM and Lu, CW and De Luna, E and Martienssen, RA and Minamino, N and Mizutani, M and Mizutani, M and Mochizuki, N and Monte, I and Mosher, R and Nagasaki, H and Nakagami, H and Naramoto, S and Nishitani, K and Ohtani, M and Okamoto, T and Okumura, M and Phillips, J and Pollak, B and Reinders, A and Rövekamp, M and Sano, R and Sawa, S and Schmid, MW and Shirakawa, M and Solano, R and Spunde, A and Suetsugu, N and Sugano, S and Sugiyama, A and Sun, R and Suzuki, Y and Takenaka, M and Takezawa, D and Tomogane, H and Tsuzuki, M and Ueda, T and Umeda, M and Ward, JM and Watanabe, Y and Yazaki, K and Yokoyama, R and Yoshitake, Y and Yotsui, I and Zachgo, S and Schmutz, J}, title = {Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome.}, journal = {Cell}, volume = {171}, number = {2}, pages = {287-304.e15}, doi = {10.1016/j.cell.2017.09.030}, pmid = {28985561}, issn = {1097-4172}, support = {BB/L014130/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adaptation, Biological ; *Biological Evolution ; Embryophyta/*genetics/physiology ; Gene Expression Regulation, Plant ; *Genome, Plant ; Marchantia/*genetics/physiology ; Molecular Sequence Annotation ; Signal Transduction ; Transcription, Genetic ; }, abstract = {The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP.}, } @article {pmid28973893, year = {2017}, author = {van Gestel, J and Tarnita, CE}, title = {On the origin of biological construction, with a focus on multicellularity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {42}, pages = {11018-11026}, pmid = {28973893}, issn = {1091-6490}, mesh = {*Biological Evolution ; Life Cycle Stages ; *Morphogenesis ; Selection, Genetic ; }, abstract = {Biology is marked by a hierarchical organization: all life consists of cells; in some cases, these cells assemble into groups, such as endosymbionts or multicellular organisms; in turn, multicellular organisms sometimes assemble into yet other groups, such as primate societies or ant colonies. The construction of new organizational layers results from hierarchical evolutionary transitions, in which biological units (e.g., cells) form groups that evolve into new units of biological organization (e.g., multicellular organisms). Despite considerable advances, there is no bottom-up, dynamical account of how, starting from the solitary ancestor, the first groups originate and subsequently evolve the organizing principles that qualify them as new units. Guided by six central questions, we propose an integrative bottom-up approach for studying the dynamics underlying hierarchical evolutionary transitions, which builds on and synthesizes existing knowledge. This approach highlights the crucial role of the ecology and development of the solitary ancestor in the emergence and subsequent evolution of groups, and it stresses the paramount importance of the life cycle: only by evaluating groups in the context of their life cycle can we unravel the evolutionary trajectory of hierarchical transitions. These insights also provide a starting point for understanding the types of subsequent organizational complexity. The central research questions outlined here naturally link existing research programs on biological construction (e.g., on cooperation, multilevel selection, self-organization, and development) and thereby help integrate knowledge stemming from diverse fields of biology.}, } @article {pmid28968519, year = {2017}, author = {Crocker, J and Ilsley, GR}, title = {Using synthetic biology to study gene regulatory evolution.}, journal = {Current opinion in genetics & development}, volume = {47}, number = {}, pages = {91-101}, doi = {10.1016/j.gde.2017.09.001}, pmid = {28968519}, issn = {1879-0380}, mesh = {Binding Sites ; Drosophila Proteins/genetics ; *Enhancer Elements, Genetic ; *Evolution, Molecular ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/*genetics ; Protein Binding ; *Synthetic Biology ; Transcription, Genetic ; }, abstract = {Transcriptional enhancers specify the precise time, level, and location of gene expression. Disentangling and characterizing the components of enhancer activity in multicellular eukaryotic development has proven challenging because enhancers contain activator and repressor binding sites for multiple factors that each exert nuanced, context-dependent control of enhancer activity. Recent advances in synthetic biology provide an almost unlimited ability to create and modify regulatory elements and networks, offering unprecedented power to study gene regulation. Here we review several studies demonstrating the utility of synthetic biology for studying enhancer function during development and evolution. These studies clearly show that synthetic biology can provide a way to reverse-engineer and reengineer transcriptional regulation in animal genomes with enormous potential for understanding evolution.}, } @article {pmid28961459, year = {2018}, author = {Deb, J and Bland, HM and Østergaard, L}, title = {Developmental cartography: coordination via hormonal and genetic interactions during gynoecium formation.}, journal = {Current opinion in plant biology}, volume = {41}, number = {}, pages = {54-60}, doi = {10.1016/j.pbi.2017.09.004}, pmid = {28961459}, issn = {1879-0356}, support = {BBS/E/J/000PR9788/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M004112/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/J/000PR9773/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/J/00000613/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J004588/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P013511/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Arabidopsis/genetics/growth & development/*physiology ; Cytokinins/metabolism ; Evolution, Molecular ; Flowers/genetics/growth & development/*physiology ; Indoleacetic Acids/metabolism ; Plant Growth Regulators/*metabolism ; Plant Leaves/genetics/growth & development/physiology ; }, abstract = {Development in multicellular organisms requires the establishment of tissue identity through polarity cues. The Arabidopsis gynoecium presents an excellent model to study this coordination, as it comprises a complex tissue structure which is established through multiple polarity systems. The gynoecium is derived from the fusion of two carpels and forms in the centre of the flower. Many regulators of carpel development also have roles in leaf development, emphasizing the evolutionary origin of carpels as modified leaves. The gynoecium can therefore be considered as having evolved from a simple setup followed by adjustment in tissue polarity to facilitate efficient reproduction. Here, we discuss concepts to understand how hormonal and genetic systems interact to pattern the gynoecium.}, } @article {pmid28959054, year = {2017}, author = {Attwood, MM and Krishnan, A and Almén, MS and Schiöth, HB}, title = {Highly diversified expansions shaped the evolution of membrane bound proteins in metazoans.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {12387}, pmid = {28959054}, issn = {2045-2322}, mesh = {Animals ; *Biodiversity ; Datasets as Topic ; Enzymes/genetics ; *Evolution, Molecular ; Membrane Proteins/*genetics ; Phylogeny ; Proteome/*genetics ; }, abstract = {The dramatic increase in membrane proteome complexity is arguably one of the most pivotal evolutionary events that underpins the origin of multicellular animals. However, the origin of a significant number of membrane families involved in metazoan development has not been clarified. In this study, we have manually curated the membrane proteomes of 22 metazoan and 2 unicellular holozoan species. We identify 123,014 membrane proteins in these 24 eukaryotic species and classify 86% of the dataset. We determine 604 functional clusters that are present from the last holozoan common ancestor (LHCA) through many metazoan species. Intriguingly, we show that more than 70% of the metazoan membrane protein families have a premetazoan origin. The data show that enzymes are more highly represented in the LHCA and expand less than threefold throughout metazoan species; in contrast to receptors that are relatively few in the LHCA but expand nearly eight fold within metazoans. Expansions related to cell adhesion, communication, immune defence, and developmental processes are shown in conjunction with emerging biological systems, such as neuronal development, cytoskeleton organization, and the adaptive immune response. This study defines the possible LHCA membrane proteome and describes the fundamental functional clusters that underlie metazoan diversity and innovation.}, } @article {pmid28943404, year = {2017}, author = {Rubin, IN and Doebeli, M}, title = {Rethinking the evolution of specialization: A model for the evolution of phenotypic heterogeneity.}, journal = {Journal of theoretical biology}, volume = {435}, number = {}, pages = {248-264}, doi = {10.1016/j.jtbi.2017.09.020}, pmid = {28943404}, issn = {1095-8541}, mesh = {Biological Evolution ; Biological Variation, Population ; *Cultural Evolution ; Environment ; *Models, Theoretical ; Mutation ; *Phenotype ; Specialization/economics/*trends ; }, abstract = {Phenotypic heterogeneity refers to genetically identical individuals that express different phenotypes, even when in the same environment. Traditionally, "bet-hedging" in fluctuating environments is offered as the explanation for the evolution of phenotypic heterogeneity. However, there are an increasing number of examples of microbial populations that display phenotypic heterogeneity in stable environments. Here we present an evolutionary model of phenotypic heterogeneity of microbial metabolism and a resultant theory for the evolution of phenotypic versus genetic specialization. We use two-dimensional adaptive dynamics to track the evolution of the population phenotype distribution of the expression of two metabolic processes with a concave trade-off. Rather than assume a Gaussian phenotype distribution, we use a Beta distribution that is capable of describing genotypes that manifest as individuals with two distinct phenotypes. Doing so, we find that environmental variation is not a necessary condition for the evolution of phenotypic heterogeneity, which can evolve as a form of specialization in a stable environment. There are two competing pressures driving the evolution of specialization: directional selection toward the evolution of phenotypic heterogeneity and disruptive selection toward genetically determined specialists. Because of the lack of a singular point in the two-dimensional adaptive dynamics and the fact that directional selection is a first order process, while disruptive selection is of second order, the evolution of phenotypic heterogeneity dominates and often precludes speciation. We find that branching, and therefore genetic specialization, occurs mainly under two conditions: the presence of a cost to maintaining a high phenotypic variance or when the effect of mutations is large. A cost to high phenotypic variance dampens the strength of selection toward phenotypic heterogeneity and, when sufficiently large, introduces a singular point into the evolutionary dynamics, effectively guaranteeing eventual branching. Large mutations allow the second order disruptive selection to dominate the first order selection toward phenotypic heterogeneity.}, } @article {pmid28938124, year = {2017}, author = {Hinshaw, SM and Makrantoni, V and Harrison, SC and Marston, AL}, title = {The Kinetochore Receptor for the Cohesin Loading Complex.}, journal = {Cell}, volume = {171}, number = {1}, pages = {72-84.e13}, pmid = {28938124}, issn = {1097-4172}, support = {/WT_/Wellcome Trust/United Kingdom ; 107827/WT_/Wellcome Trust/United Kingdom ; P41 GM103403/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Cycle Proteins/*metabolism ; Centromere/metabolism ; Chromosomal Proteins, Non-Histone/*metabolism ; Cytoskeletal Proteins/metabolism ; Kinetochores/*metabolism ; Multiprotein Complexes/metabolism ; Phosphorylation ; Phylogeny ; Saccharomyces cerevisiae/cytology/*metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; X-Ray Diffraction ; }, abstract = {The ring-shaped cohesin complex brings together distant DNA domains to maintain, express, and segregate the genome. Establishing specific chromosomal linkages depends on cohesin recruitment to defined loci. One such locus is the budding yeast centromere, which is a paradigm for targeted cohesin loading. The kinetochore, a multiprotein complex that connects centromeres to microtubules, drives the recruitment of high levels of cohesin to link sister chromatids together. We have exploited this system to determine the mechanism of specific cohesin recruitment. We show that phosphorylation of the Ctf19 kinetochore protein by a conserved kinase, DDK, provides a binding site for the Scc2/4 cohesin loading complex, thereby directing cohesin loading to centromeres. A similar mechanism targets cohesin to chromosomes in vertebrates. These findings represent a complete molecular description of targeted cohesin loading, a phenomenon with wide-ranging importance in chromosome segregation and, in multicellular organisms, transcription regulation.}, } @article {pmid28936730, year = {2017}, author = {Conigliaro, A and Fontana, S and Raimondo, S and Alessandro, R}, title = {Exosomes: Nanocarriers of Biological Messages.}, journal = {Advances in experimental medicine and biology}, volume = {998}, number = {}, pages = {23-43}, doi = {10.1007/978-981-10-4397-0_2}, pmid = {28936730}, issn = {0065-2598}, mesh = {Animals ; Exosomes/genetics/*metabolism/ultrastructure ; Humans ; Intracellular Signaling Peptides and Proteins/*metabolism ; *Lipid Metabolism ; *Nanoparticles ; Nucleic Acids/*metabolism ; Organelle Size ; Protein Transport ; *Signal Transduction ; }, abstract = {Cell-cell communication is crucial to maintain homeostasis in multicellular organism. Cells communicate each other by direct contact or by releasing factors that, soluble or packaged in membrane vesicles, can reach different regions of the organism. To date numerous studies highlighted the existence of several types of extracellular vesicles that, differing for dimension, origin and contents, play a role in physiological and/or pathological processes. Among extracellular vesicles, exosomes are emerging as efficient players to modulate target cells phenotype and as new non-invasive diagnostic and prognostic tools in multiple diseases. They, in fact, strictly reflect the type and functional status of the producing cells and are able to deliver their contents even over a long distance. The results accumulated in the last two decades and collected in this chapter, indicated that exosomes, can carry RNAs, microRNAs, long non-coding RNAs, DNA, lipids, metabolites and proteins; a deeper understanding of their contents is therefore needed to get the most from this incredible cell product.}, } @article {pmid28923586, year = {2017}, author = {Dennis, JW}, title = {Genetic code asymmetry supports diversity through experimentation with posttranslational modifications.}, journal = {Current opinion in chemical biology}, volume = {41}, number = {}, pages = {1-11}, doi = {10.1016/j.cbpa.2017.08.012}, pmid = {28923586}, issn = {1879-0402}, mesh = {Animals ; Evolution, Molecular ; *Genetic Code ; Humans ; Protein Processing, Post-Translational/*genetics ; Proteins/*genetics/*metabolism ; Selection, Genetic ; }, abstract = {Protein N-glycosylation has been identified in all three domains of life presumably conserved for its early role in glycoprotein folding. However, the N-glycans added to proteins in the secretory pathway of multicellular organisms are remodeling in the Golgi, increasing structural diversity exponentially and adding new layers of functionality in immunity, metabolism and other systems. The branching and elongation of N-glycan chains found on cell surface receptors generates a gradation of affinities for carbohydrate-binding proteins, the galectin, selectin and siglec families. These interactions adapt cellular responsiveness to environmental conditions, but their complexity presents a daunting challenge to drug design. To gain further insight, I review how N-glycans biosynthesis and biophysical properties provide a selective advantage in the form of tunable and ultrasensitive stimulus-response relationships. In addition, the N-glycosylation motif favors step-wise mutational experimentation with sites. Glycoproteins display accelerated evolution during vertebrate radiation, and the encoding asymmetry of NXS/T(X≠P) has left behind phylogenetic evidence suggesting that the genetic code may have been selected to optimize diversity in part through emerging posttranslational modifications.}, } @article {pmid28916791, year = {2017}, author = {Yamazaki, T and Ichihara, K and Suzuki, R and Oshima, K and Miyamura, S and Kuwano, K and Toyoda, A and Suzuki, Y and Sugano, S and Hattori, M and Kawano, S}, title = {Genomic structure and evolution of the mating type locus in the green seaweed Ulva partita.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {11679}, pmid = {28916791}, issn = {2045-2322}, mesh = {Chromosomes ; Computational Biology ; DNA, Algal/genetics ; *Evolution, Molecular ; *Gene Order ; *Genetic Loci ; *Genomics ; High-Throughput Nucleotide Sequencing ; Seaweed/*genetics ; Ulva/*genetics ; }, abstract = {The evolution of sex chromosomes and mating loci in organisms with UV systems of sex/mating type determination in haploid phases via genes on UV chromosomes is not well understood. We report the structure of the mating type (MT) locus and its evolutionary history in the green seaweed Ulva partita, which is a multicellular organism with an isomorphic haploid-diploid life cycle and mating type determination in the haploid phase. Comprehensive comparison of a total of 12.0 and 16.6 Gb of genomic next-generation sequencing data for mt[-] and mt[+] strains identified highly rearranged MT loci of 1.0 and 1.5 Mb in size and containing 46 and 67 genes, respectively, including 23 gametologs. Molecular evolutionary analyses suggested that the MT loci diverged over a prolonged period in the individual mating types after their establishment in an ancestor. A gene encoding an RWP-RK domain-containing protein was found in the mt[-] MT locus but was not an ortholog of the chlorophycean mating type determination gene MID. Taken together, our results suggest that the genomic structure and its evolutionary history in the U. partita MT locus are similar to those on other UV chromosomes and that the MT locus genes are quite different from those of Chlorophyceae.}, } @article {pmid28916376, year = {2017}, author = {Peng, L and Wang, L and Yang, YF and Zou, MM and He, WY and Wang, Y and Wang, Q and Vasseur, L and You, MS}, title = {Transcriptome profiling of the Plutella xylostella (Lepidoptera: Plutellidae) ovary reveals genes involved in oogenesis.}, journal = {Gene}, volume = {637}, number = {}, pages = {90-99}, doi = {10.1016/j.gene.2017.09.020}, pmid = {28916376}, issn = {1879-0038}, mesh = {Animals ; Female ; Gene Expression Profiling/*methods ; Gene Regulatory Networks ; Insect Proteins/*genetics/metabolism ; Insecticide Resistance/*genetics ; Moths/*genetics/growth & development/metabolism ; *Oogenesis ; Ovary/growth & development/*metabolism ; Phylogeny ; Reproduction ; *Transcriptome ; }, abstract = {BACKGROUND: As a specialized organ, the insect ovary performs valuable functions by ensuring fecundity and population survival. Oogenesis is the complex physiological process resulting in the production of mature eggs, which are involved in epigenetic programming, germ cell behavior, cell cycle regulation, etc. Identification of the genes involved in ovary development and oogenesis is critical to better understand the reproductive biology and screening for the potential molecular targets in Plutella xylostella, a worldwide destructive pest of economically major crops.

RESULTS: Based on transcriptome sequencing, a total of 7.88Gb clean nucleotides was obtained, with 19,934 genes and 1861 new transcripts being identified. Expression profiling indicated that 61.7% of the genes were expressed (FPKM≥1) in the P. xylostella ovary. GO annotation showed that the pathways of multicellular organism reproduction and multicellular organism reproduction process, as well as gamete generation and chorion were significantly enriched. Processes that were most likely relevant to reproduction included the spliceosome, ubiquitin mediated proteolysis, endocytosis, PI3K-Akt signaling pathway, insulin signaling pathway, cAMP signaling pathway, and focal adhesion were identified in the top 20 'highly represented' KEGG pathways. Functional genes involved in oogenesis were further analyzed and validated by qRT-PCR to show their potential predominant roles in P. xylostella reproduction.

CONCLUSIONS: Our newly developed P. xylostella ovary transcriptome provides an overview of the gene expression profiling in this specialized tissue and the functional gene network closely related to the ovary development and oogenesis. This is the first genome-wide transcriptome dataset of P. xylostella ovary that includes a subset of functionally activated genes. This global approach will be the basis for further studies on molecular mechanisms of P. xylostella reproduction aimed at screening potential molecular targets for integrated pest management.}, } @article {pmid28904210, year = {2017}, author = {Willy, NM and Ferguson, JP and Huber, SD and Heidotting, SP and Aygün, E and Wurm, SA and Johnston-Halperin, E and Poirier, MG and Kural, C}, title = {Membrane mechanics govern spatiotemporal heterogeneity of endocytic clathrin coat dynamics.}, journal = {Molecular biology of the cell}, volume = {28}, number = {24}, pages = {3480-3488}, pmid = {28904210}, issn = {1939-4586}, support = {R01 AI121124/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Biomechanical Phenomena ; Cell Line, Tumor ; Cell Membrane/metabolism/physiology ; Cells, Cultured ; Chlorocebus aethiops ; Clathrin/metabolism ; Clathrin-Coated Vesicles/metabolism/*physiology ; Coated Pits, Cell-Membrane/metabolism/physiology ; Cytoplasm/metabolism ; Drosophila ; Endocytosis/physiology ; Humans ; Spatio-Temporal Analysis ; }, abstract = {Dynamics of endocytic clathrin-coated structures can be remarkably divergent across different cell types, cells within the same culture, or even distinct surfaces of the same cell. The origin of this astounding heterogeneity remains to be elucidated. Here we show that cellular processes associated with changes in effective plasma membrane tension induce significant spatiotemporal alterations in endocytic clathrin coat dynamics. Spatiotemporal heterogeneity of clathrin coat dynamics is also observed during morphological changes taking place within developing multicellular organisms. These findings suggest that tension gradients can lead to patterning and differentiation of tissues through mechanoregulation of clathrin-mediated endocytosis.}, } @article {pmid28904062, year = {2017}, author = {Huang, Y and Wang, S and Guo, Q and Kessel, S and Rubinoff, I and Chan, LL and Li, P and Liu, Y and Qiu, J and Zhou, C}, title = {Optical Coherence Tomography Detects Necrotic Regions and Volumetrically Quantifies Multicellular Tumor Spheroids.}, journal = {Cancer research}, volume = {77}, number = {21}, pages = {6011-6020}, pmid = {28904062}, issn = {1538-7445}, support = {R15 EB019704/EB/NIBIB NIH HHS/United States ; R21 EY026380/EY/NEI NIH HHS/United States ; }, mesh = {Cell Culture Techniques/methods ; Cell Line, Tumor ; Cell Survival ; HCT116 Cells ; Humans ; Imaging, Three-Dimensional/*methods ; Necrosis ; Neoplasms/*diagnostic imaging ; Reproducibility of Results ; Spheroids, Cellular/*pathology ; Time Factors ; Tomography, Optical Coherence/*methods ; }, abstract = {Three-dimensional (3D) tumor spheroid models have gained increased recognition as important tools in cancer research and anticancer drug development. However, currently available imaging approaches used in high-throughput screening drug discovery platforms, for example, bright-field, phase contrast, and fluorescence microscopies, are unable to resolve 3D structures deep inside (>50 μm) tumor spheroids. In this study, we established a label-free, noninvasive optical coherence tomography (OCT) imaging platform to characterize 3D morphologic and physiologic information of multicellular tumor spheroids (MCTS) growing from approximately 250 to 600 μm in height over 21 days. In particular, tumor spheroids of two cell lines, glioblastoma (U-87MG) and colorectal carcinoma (HCT116), exhibited distinctive evolutions in their geometric shapes at late growth stages. Volumes of MCTS were accurately quantified using a voxel-based approach without presumptions of their geometries. In contrast, conventional diameter-based volume calculations assuming perfect spherical shape resulted in large quantification errors. Furthermore, we successfully detected necrotic regions within these tumor spheroids based on increased intrinsic optical attenuation, suggesting a promising alternative of label-free viability tests in tumor spheroids. Therefore, OCT can serve as a promising imaging modality to characterize morphologic and physiologic features of MCTS, showing great potential for high-throughput drug screening. Cancer Res; 77(21); 6011-20. ©2017 AACR.}, } @article {pmid28899581, year = {2017}, author = {Kennedy, P and Baron, G and Qiu, B and Freitak, D and Helanterä, H and Hunt, ER and Manfredini, F and O'Shea-Wheller, T and Patalano, S and Pull, CD and Sasaki, T and Taylor, D and Wyatt, CDR and Sumner, S}, title = {Deconstructing Superorganisms and Societies to Address Big Questions in Biology.}, journal = {Trends in ecology & evolution}, volume = {32}, number = {11}, pages = {861-872}, doi = {10.1016/j.tree.2017.08.004}, pmid = {28899581}, issn = {1872-8383}, mesh = {Animals ; *Behavior, Animal ; Biological Evolution ; Hymenoptera/*physiology ; Isoptera/*physiology ; *Social Behavior ; }, abstract = {Social insect societies are long-standing models for understanding social behaviour and evolution. Unlike other advanced biological societies (such as the multicellular body), the component parts of social insect societies can be easily deconstructed and manipulated. Recent methodological and theoretical innovations have exploited this trait to address an expanded range of biological questions. We illustrate the broadening range of biological insight coming from social insect biology with four examples. These new frontiers promote open-minded, interdisciplinary exploration of one of the richest and most complex of biological phenomena: sociality.}, } @article {pmid28898926, year = {2018}, author = {Mosaffa, P and Rodríguez-Ferran, A and Muñoz, JJ}, title = {Hybrid cell-centred/vertex model for multicellular systems with equilibrium-preserving remodelling.}, journal = {International journal for numerical methods in biomedical engineering}, volume = {34}, number = {3}, pages = {}, doi = {10.1002/cnm.2928}, pmid = {28898926}, issn = {2040-7947}, mesh = {*Biomechanical Phenomena ; Humans ; Models, Biological ; }, abstract = {We present a hybrid cell-centred/vertex model for mechanically simulating planar cellular monolayers undergoing cell reorganisation. Cell centres are represented by a triangular nodal network, while the cell boundaries are formed by an associated vertex network. The two networks are coupled through a kinematic constraint which we allow to relax progressively. Special attention is paid to the change of cell-cell connectivity due to cell reorganisation or remodelling events. We handle these situations by using a variable resting length and applying an Equilibrium-Preserving Mapping on the new connectivity, which computes a new set of resting lengths that preserve nodal and vertex equilibrium. We illustrate the properties of the model by simulating monolayers subjected to imposed extension and during a wound healing process. The evolution of forces and the Equilibrium-Preserving Mapping are analysed during the remodelling events. As a by-product, the proposed technique enables to recover fully vertex or fully cell-centred models in a seamless manner by modifying a numerical parameter of the model.}, } @article {pmid28898640, year = {2017}, author = {Ferrer-Bonet, M and Ruiz-Trillo, I}, title = {Capsaspora owczarzaki.}, journal = {Current biology : CB}, volume = {27}, number = {17}, pages = {R829-R830}, doi = {10.1016/j.cub.2017.05.074}, pmid = {28898640}, issn = {1879-0445}, mesh = {Animals ; *Biological Evolution ; Eukaryota/*classification/*cytology/genetics ; Genome ; Phylogeny ; }, abstract = {Capsaspora owczarzaki is a unicellular eukaryote that is becoming pivotal to understanding the origin of animal multicellularity.}, } @article {pmid28893859, year = {2018}, author = {Rübsam, M and Broussard, JA and Wickström, SA and Nekrasova, O and Green, KJ and Niessen, CM}, title = {Adherens Junctions and Desmosomes Coordinate Mechanics and Signaling to Orchestrate Tissue Morphogenesis and Function: An Evolutionary Perspective.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, pmid = {28893859}, issn = {1943-0264}, support = {R01 AR043380/AR/NIAMS NIH HHS/United States ; T32 AR007593/AR/NIAMS NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; R01 CA122151/CA/NCI NIH HHS/United States ; R01 AR041836/AR/NIAMS NIH HHS/United States ; R01 CA228196/CA/NCI NIH HHS/United States ; P30 AR057216/AR/NIAMS NIH HHS/United States ; R37 AR043380/AR/NIAMS NIH HHS/United States ; }, mesh = {Adherens Junctions/genetics/*physiology ; Animals ; *Biological Evolution ; Cell Polarity ; Desmosomes/genetics/*physiology ; Epithelial Cells/physiology ; Signal Transduction/*physiology ; }, abstract = {Cadherin-based adherens junctions (AJs) and desmosomes are crucial to couple intercellular adhesion to the actin or intermediate filament cytoskeletons, respectively. As such, these intercellular junctions are essential to provide not only integrity to epithelia and other tissues but also the mechanical machinery necessary to execute complex morphogenetic and homeostatic intercellular rearrangements. Moreover, these spatially defined junctions serve as signaling hubs that integrate mechanical and chemical pathways to coordinate tissue architecture with behavior. This review takes an evolutionary perspective on how the emergence of these two essential intercellular junctions at key points during the evolution of multicellular animals afforded metazoans with new opportunities to integrate adhesion, cytoskeletal dynamics, and signaling. We discuss known literature on cross-talk between the two junctions and, using the skin epidermis as an example, provide a model for how these two junctions function in concert to orchestrate tissue organization and function.}, } @article {pmid28889384, year = {2018}, author = {Yoshida, T and Okuyama, H and Endo, H and Inoue, M}, title = {Spheroid Cultures of Primary Urothelial Cancer Cells: Cancer Tissue-Originated Spheroid (CTOS) Method.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1655}, number = {}, pages = {145-153}, doi = {10.1007/978-1-4939-7234-0_12}, pmid = {28889384}, issn = {1940-6029}, mesh = {Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Separation/methods ; Drug Resistance, Neoplasm ; Humans ; *Primary Cell Culture/methods ; *Spheroids, Cellular ; *Tumor Cells, Cultured ; Urinary Bladder Neoplasms/*pathology ; }, abstract = {Increasingly, it has been recognized that studying cancer samples from individual patients is important for the development of effective therapeutic strategies and in endeavors to overcome therapy resistance. Primary cultures of cancer cells acutely dissected from individual patients can provide a platform that enables the study and characterization of individual tumors. To that end, we have developed a method for preparing cancer cells in the form of multi-cellular spheroids. The cells can be derived from patient tumors (primary cells), from patient-derived xenografts, or from genetically- or chemically induced animal tumors. This method of culturing spheroids composed of cells derived from cancer tissues can be applied to various types of cancer, including urothelial cancer. The method is based on the principle of retaining cell-cell contact throughout cancer cell preparation and culturing. The first step is a partial digestion of the tumor specimen into small fragments; these fragments spontaneously form spheroidal shapes within several hours. The spheroid is referred to as a cancer tissue-originated spheroid (CTOS). The advantage of the CTOS method is that it allows one to prepare pure cancer cells at high yield. CTOSs can be stably cultured in serum-free conditions. The CTOS method can be applied to drug sensitivity assays, drug screening, and analyses of intracellular signaling. Moreover, the CTOS method provides a platform for studying the nature of cancer cell clusters.}, } @article {pmid28889015, year = {2017}, author = {He, HH and Chi, YM and Yuan, K and Li, XY and Weng, SP and He, JG and Chen, YH}, title = {Functional characterization of a reactive oxygen species modulator 1 gene in Litopenaeus vannamei.}, journal = {Fish & shellfish immunology}, volume = {70}, number = {}, pages = {270-279}, doi = {10.1016/j.fsi.2017.09.024}, pmid = {28889015}, issn = {1095-9947}, mesh = {Amino Acid Sequence ; Animals ; Arthropod Proteins/*genetics/*immunology ; Base Sequence ; Cell Line ; Drosophila melanogaster ; Gene Expression Regulation ; *Immunity, Innate ; Penaeidae/*genetics/*immunology ; Phylogeny ; Reactive Oxygen Species/*metabolism ; Sequence Alignment ; Vibrio alginolyticus/physiology ; White spot syndrome virus 1/physiology ; }, abstract = {Reactive oxygen species (ROS) imparts a dual effect on multicellular organisms, wherein high levels are usually harmful, and low levels could facilitate in combating pathogenic microorganisms; therefore, the regulation of ROS production is critical. Previous studies have suggested that ROS contributes to resistance to the white spot syndrome virus (WSSV) or Vibrio alginolyticus in Litopenaeus vannamei. However, the regulation of ROS metabolism in L. vannamei remains elusive. In the present study, we proved that the overexpression of L. vannamei reactive oxygen species modulator 1 (LvROMO1) increases ROS production in Drosophila Schneider 2 (S2) cells. Real-time RT-PCR analysis indicated that LvROMO1 is induced by WSSV or V. alginolyticus infection and β-glucan or microcystin (MC-LR) injection. Further investigation showed that LvROMO1 responding to MC-LR, thereby inducing hemocytes to undergo apoptosis, and ultimately resulting in hepatopancreatic damage. And LvROMO1 downregulation induced an increase in the cumulative mortality of WSSV-infected shrimp by reducing ROS production and suppressing the expression of antimicrobial peptides genes. The findings of present study suggest that LvROMO1 plays an important role in ROS production in L. vannamei and is involved in innate immunity.}, } @article {pmid28866006, year = {2017}, author = {Witting, L}, title = {The natural selection of metabolism and mass selects allometric transitions from prokaryotes to mammals.}, journal = {Theoretical population biology}, volume = {117}, number = {}, pages = {23-42}, doi = {10.1016/j.tpb.2017.08.005}, pmid = {28866006}, issn = {1096-0325}, mesh = {Animals ; Basal Metabolism ; Biological Evolution ; Body Size ; Ecology ; Mammals/*metabolism ; Models, Biological ; Prokaryotic Cells/*metabolism ; Selection, Genetic/*physiology ; }, abstract = {The exponents of inter-specific allometries for several life history (metabolism, lifespan, reproductive rate, survival) and ecological (population density, home range) traits may evolve from the spatial dimensionality (d) of the intra-specific interactive competition that selects net assimilated energy into mass, with 1∕4 exponents being the two-dimensional (2D) case of the more general 1∕2d (Witting, 1995). While the exponents for mass-specific metabolism cluster around the predicted -1/4 and -1/6 in terrestrial and pelagic vertebrates, the allometries of mobile organisms are more diverse than the prediction. An exponent around zero has been reported for protists and protozoa (Makarieva et al., 2005, 2008), and the exponent appears to be strongly positive in prokaryotes with a value of about 5/6 (DeLong et al., 2010). I show that the natural selection of metabolism and mass is sufficient to explain exponents for mass-specific metabolism that decline from 5/6 over zero to -1∕6 in 3D, and from 3/4 over zero to -1∕4 in 2D. These results suggest that mass-specific metabolism is selected as the pace of the resource handling that generates net energy for self-replication and the selection of mass, with the decline in the metabolic exponent following from a decline in the importance of mass-specific metabolism for the selection of mass. The body mass variation in prokaryotes is found to be selected from primary variation in mass-specific metabolism, while the variation in multicellular animals is selected from primary variation in the handling and/or densities of the underlying resources, with protists and protozoa being selected as an intermediate lifeform.}, } @article {pmid28864113, year = {2017}, author = {Li, DD and Luo, Z and Chen, GH and Song, YF and Wei, CC and Pan, YX}, title = {Identification of apoptosis-related genes Bcl2 and Bax from yellow catfish Pelteobagrus fulvidraco and their transcriptional responses to waterborne and dietborne zinc exposure.}, journal = {Gene}, volume = {633}, number = {}, pages = {1-8}, doi = {10.1016/j.gene.2017.08.029}, pmid = {28864113}, issn = {1879-0038}, mesh = {Animals ; Apoptosis/*genetics/physiology ; Catfishes/*genetics/metabolism ; DNA, Complementary/genetics ; Down-Regulation ; Environmental Exposure ; Fish Proteins/classification/*genetics/physiology ; Lipid Metabolism/genetics ; Liver/metabolism ; Phylogeny ; RNA, Messenger/genetics/metabolism ; *Transcription, Genetic ; Up-Regulation ; Water/chemistry ; Zinc/analysis/*metabolism ; bcl-2-Associated X Protein/classification/*genetics/physiology ; bcl-Associated Death Protein/classification/*genetics/physiology ; }, abstract = {Apoptosis plays a key role in the physiology of multicellular organisms, and has been well studied in mammals, but not in teleosts. Zinc (Zn) has been shown to be an important regulator of apoptosis and apoptosis involves in the regulation of lipid metabolism. Moreover, our recent study indicated that waterborne and dietborne Zn exposure differently influenced lipid metabolism in Pelteobagrus fulvidraco, but further mechanism remained unknown. The hypothesis of the present study is that apoptosis mediated the Zn-induced changes of lipid metabolism of P. fulvidraco subjected to different exposure pathways. To this end, we cloned full-length cDNA sequences of Bcl2 and three Bax subtypes involved in apoptosis in P. fulvidraco, explored their mRNA expressions in responses to different Zn exposure pathways. Bcl2 and three Bax subtypes shared similar domain structure as typical pro- and anti-apoptotic Bcl2 family members. Their mRNAs were widely expressed among various tissues, but at variable levels. Waterborne Zn exposure down-regulated mRNA levels of Baxg and ratios of Baxa/Bcl2, and Baxg/Bcl2, but showed no significant effects on mRNA abundances of Bcl2, Baxa and Baxb, and the ratio of Baxb/Bcl2. In contrast, dietborne Zn exposure up-regulated mRNA levels of Bcl2, Baxa, Baxb and Baxg, but reduced the ratios of Baxa/Bcl2, Baxb/Bcl2, and Baxg/Bcl2. Considering their important roles of these genes in apoptosis induced by Zn, apoptosis may mediate the Zn-induced changes of hepatic lipid metabolism of Pelteobagrus fulvidraco under different Zn exposure pathways. For the first time, we characterized the full-length cDNA sequences of Bcl2 and three Bax subtypes, determined their expression profiles and transcriptional responses to different Zn exposure pathways, which would contribute to our understanding of the molecular basis of apoptosis, and also provide new insights into physiological responses to different Zn exposure pathways.}, } @article {pmid28862769, year = {2018}, author = {Yuan, H and Silberstein, SD}, title = {Histamine and Migraine.}, journal = {Headache}, volume = {58}, number = {1}, pages = {184-193}, doi = {10.1111/head.13164}, pmid = {28862769}, issn = {1526-4610}, mesh = {Central Nervous System/*metabolism ; Histamine/*metabolism ; Homeostasis ; Humans ; Migraine Disorders/*metabolism/*pathology ; Neurotransmitter Agents/physiology ; }, abstract = {BACKGROUND: Histamine is an ancient "tissue amine" preceding multicellular organisms. In the central nervous system (CNS), its fibers originate solely from the tuberomammillary nucleus and travel throughout the brain. It is mainly responsible for wakefulness, energy homeostasis, and memory consolidation. Recently, several studies suggest a potential role of histamine in migraine pathogenesis and management.

METHODS: Narrative review of current literature regarding histamine and migraine.

RESULTS: Histamine plays a crucial role in migraine pathogenesis: sustaining the neurogenic inflammation pathway. Interaction between mast cells (MC) and calcitonin-gene related protein (CGRP) results in sensitization of trigeminal afferents and trigeminal ganglia (TG). Histamine binds with differing affinities to four different histaminergic G-protein coupled receptors, activating protein kinases, or triggering calcium release with subsequent mode of actions. Histamine 1 receptor (H1 R) and histamine 2 receptor (H2 R) antagonists are frequently used for the treatment of allergy and gastric acid secretion, respectively, but their antagonism is probably ineffective for migraine. Histamine 3 receptor (H3 R) and histamine 4 receptor (H4 R) have a threefold higher affinity than H1 R/H2 R for histamine and are found almost exclusively on neurons and immune tissues, respectively. H3 R acts as an autoreceptor or as a heteroreceptor, lowering the release of histamine and other neurotransmitters. This is a potential target for anti-nociception and anti-neurogenic inflammation. To date, several small clinical trials using low dose histamine or N[α] -methylhistamine have demonstrated migraine prophylactic efficacy, probably via H3 R or other undetermined pathways.

CONCLUSION: The histamine system interacts with multiple regions in the CNS and may hypothetically modulate the migraine response. Low dose histamine may be a promising option for migraine prevention.}, } @article {pmid28861094, year = {2017}, author = {Rauch, C and Jahns, P and Tielens, AGM and Gould, SB and Martin, WF}, title = {On Being the Right Size as an Animal with Plastids.}, journal = {Frontiers in plant science}, volume = {8}, number = {}, pages = {1402}, pmid = {28861094}, issn = {1664-462X}, abstract = {Plastids typically reside in plant or algal cells-with one notable exception. There is one group of multicellular animals, sea slugs in the order Sacoglossa, members of which feed on siphonaceous algae. The slugs sequester the ingested plastids in the cytosol of cells in their digestive gland, giving the animals the color of leaves. In a few species of slugs, including members of the genus Elysia, the stolen plastids (kleptoplasts) can remain morphologically intact for weeks and months, surrounded by the animal cytosol, which is separated from the plastid stroma by only the inner and outer plastid membranes. The kleptoplasts of the Sacoglossa are the only case described so far in nature where plastids interface directly with the metazoan cytosol. That makes them interesting in their own right, but it has also led to the idea that it might someday be possible to engineer photosynthetic animals. Is that really possible? And if so, how big would the photosynthetic organs of such animals need to be? Here we provide two sets of calculations: one based on a best case scenario assuming that animals with kleptoplasts can be, on a per cm[2] basis, as efficient at CO2 fixation as maize leaves, and one based on [14]CO2 fixation rates measured in plastid-bearing sea slugs. We also tabulate an overview of the literature going back to 1970 reporting direct measurements or indirect estimates of the CO2 fixing capabilities of Sacoglossan slugs with plastids.}, } @article {pmid28859625, year = {2017}, author = {Koch, R and Kupczok, A and Stucken, K and Ilhan, J and Hammerschmidt, K and Dagan, T}, title = {Plasticity first: molecular signatures of a complex morphological trait in filamentous cyanobacteria.}, journal = {BMC evolutionary biology}, volume = {17}, number = {1}, pages = {209}, pmid = {28859625}, issn = {1471-2148}, support = {281357/ERC_/European Research Council/International ; }, mesh = {*Biological Evolution ; Cyanobacteria/*classification/cytology/*genetics/metabolism ; Evolution, Molecular ; Gene Expression Regulation ; Phenotype ; *Regulatory Sequences, Nucleic Acid ; Sucrose/metabolism ; Transcription Initiation Site ; }, abstract = {BACKGROUND: Filamentous cyanobacteria that differentiate multiple cell types are considered the peak of prokaryotic complexity and their evolution has been studied in the context of multicellularity origins. Species that form true-branching filaments exemplify the most complex cyanobacteria. However, the mechanisms underlying the true-branching morphology remain poorly understood despite of several investigations that focused on the identification of novel genes or pathways. An alternative route for the evolution of novel traits is based on existing phenotypic plasticity. According to that scenario - termed genetic assimilation - the fixation of a novel phenotype precedes the fixation of the genotype.

RESULTS: Here we show that the evolution of transcriptional regulatory elements constitutes a major mechanism for the evolution of new traits. We found that supplementation with sucrose reconstitutes the ancestral branchless phenotype of two true-branching Fischerella species and compared the transcription start sites (TSSs) between the two phenotypic states. Our analysis uncovers several orthologous TSSs whose transcription level is correlated with the true-branching phenotype. These TSSs are found in genes that encode components of the septosome and elongasome (e.g., fraC and mreB).

CONCLUSIONS: The concept of genetic assimilation supplies a tenable explanation for the evolution of novel traits but testing its feasibility is hindered by the inability to recreate and study the evolution of present-day traits. We present a novel approach to examine transcription data for the plasticity first route and provide evidence for its occurrence during the evolution of complex colony morphology in true-branching cyanobacteria. Our results reveal a route for evolution of the true-branching phenotype in cyanobacteria via modification of the transcription level of pre-existing genes. Our study supplies evidence for the 'plasticity-first' hypothesis and highlights the importance of transcriptional regulation in the evolution of novel traits.}, } @article {pmid28859623, year = {2017}, author = {Patel, VD and Capra, JA}, title = {Ancient human miRNAs are more likely to have broad functions and disease associations than young miRNAs.}, journal = {BMC genomics}, volume = {18}, number = {1}, pages = {672}, pmid = {28859623}, issn = {1471-2164}, mesh = {Animals ; Disease/*genetics ; *Evolution, Molecular ; Humans ; MicroRNAs/*genetics ; Phylogeny ; Transcriptome ; }, abstract = {BACKGROUND: microRNAs (miRNAs) are essential to the regulation of gene expression in eukaryotes, and improper expression of miRNAs contributes to hundreds of diseases. Despite the essential functions of miRNAs, the evolutionary dynamics of how they are integrated into existing gene regulatory and functional networks is not well understood. Knowledge of the origin and evolutionary history a gene has proven informative about its functions and disease associations; we hypothesize that incorporating the evolutionary origins of miRNAs into analyses will help resolve differences in their functional dynamics and how they influence disease.

RESULTS: We computed the phylogenetic age of miRNAs across 146 species and quantified the relationship between human miRNA age and several functional attributes. Older miRNAs are significantly more likely to be associated with disease than younger miRNAs, and the number of associated diseases increases with age. As has been observed for genes, the miRNAs associated with different diseases have different age profiles. For example, human miRNAs implicated in cancer are enriched for origins near the dawn of animal multicellularity. Consistent with the increasing contribution of miRNAs to disease with age, older miRNAs target more genes than younger miRNAs, and older miRNAs are expressed in significantly more tissues. Furthermore, miRNAs of all ages exhibit a strong preference to target older genes; 93% of validated miRNA gene targets were in existence at the origin of the targeting miRNA. Finally, we find that human miRNAs in evolutionarily related families are more similar in their targets and expression profiles than unrelated miRNAs.

CONCLUSIONS: Considering the evolutionary origin and history of a miRNA provides useful context for the analysis of its function. Consistent with recent work in Drosophila, our results support a model in which miRNAs increase their expression and functional regulatory interactions over evolutionary time, and thus older miRNAs have increased potential to cause disease. We anticipate that these patterns hold across mammalian species; however, comprehensively evaluating them will require refining miRNA annotations across species and collecting functional data in non-human systems.}, } @article {pmid28859501, year = {2017}, author = {Csaba, G}, title = {Is there a hormonal regulation of phagocytosis at unicellular and multicellular levels? A critical review.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {64}, number = {4}, pages = {357-372}, doi = {10.1556/030.64.2017.024}, pmid = {28859501}, issn = {1217-8950}, mesh = {Animals ; Hormones/*immunology ; Humans ; Macrophages/cytology/*immunology ; *Phagocytosis ; }, abstract = {Phagocytosis is an ancient cell function, which is similar at unicellular and multicellular levels. Unicells synthesize, store, and secrete multicellular (mammalian) hormones, which influence their phagocytosis. Amino acid hormones, such as histamine, serotonin, epinephrine, and melatonin stimulate phagocytosis, whereas peptide hormones, such as adrenocorticotropic hormone (ACTH), insulin, opioids, arginine vasopressin, and atrial natriuretic peptide decreased it, independently on their chemical structure or function in multicellulars. Macrophage phagocytosis of multicellulars is also stimulated by amino acid hormones, such as histamine, epinephrine, melatonin, and thyroid hormones, however, the effect of peptide hormones is not uniform: prolactin, insulin, glucagon, somatostatin, and leptin have positive effects, whereas ACTH, human chorionic gonadotropin, opioids, and ghrelin have negative ones. Steroid hormones, such as estrogen, hydrocortisone, and dexamethasone are stimulating macrophage phagocytosis, whereas progesterone, aldosterone, and testosterone are depressing it. Considering the data and observations there is not a specific phagocytosis hormone, or a hormonal regulation of phagocytosis neither unicellular, nor multicellular level, however, hormones having specific functions in multicellulars also influence phagocytosis at both levels universally (in unicellulars) or individually (in macrophages). Nevertheless, the hormonal influence cannot be neglected, as phagocytosis (as a function) is rather sensitive to minute dose of hormones and endocrine disruptors. The hormonal influence of phagocytosis by macrophages can be deduced to the events at unicellular level.}, } @article {pmid28856734, year = {2017}, author = {Deines, P and Lachnit, T and Bosch, TCG}, title = {Competing forces maintain the Hydra metaorganism.}, journal = {Immunological reviews}, volume = {279}, number = {1}, pages = {123-136}, doi = {10.1111/imr.12564}, pmid = {28856734}, issn = {1600-065X}, mesh = {Animals ; *Biological Evolution ; Homeostasis ; Host-Pathogen Interactions ; Humans ; Hydra/*physiology ; *Immunity, Innate ; Symbiosis ; }, abstract = {Our conventional view of multicellular organisms often overlooks the fact that they are metaorganisms. They consist of a host, which is comprised of both a community of self-replicating cells that can compete as well as cooperate and a community of associated microorganisms. This newly discovered complexity raises a profound challenge: How to maintain such a multicellular association that includes independently replicating units and even different genotypes? Here, we identify competing forces acting at the host tissue level, the host-microbe interface, and within the microbial community as key factors to maintain the metaorganism Hydra. Maintenance of host tissue integrity, as well as proper regulation and management of the multiorganismic interactions are fundamental to organismal survival and health. Findings derived from the in vivo context of the Hydra model may provide one of the simplest possible systems to address questions on how a metaorganism is established and remains in balance over time.}, } @article {pmid28852499, year = {2017}, author = {Buzanskas, ME and Grossi, DDA and Ventura, RV and Schenkel, FS and Chud, TCS and Stafuzza, NB and Rola, LD and Meirelles, SLC and Mokry, FB and Mudadu, MA and Higa, RH and da Silva, MVGB and de Alencar, MM and Regitano, LCA and Munari, DP}, title = {Candidate genes for male and female reproductive traits in Canchim beef cattle.}, journal = {Journal of animal science and biotechnology}, volume = {8}, number = {}, pages = {67}, pmid = {28852499}, issn = {1674-9782}, abstract = {BACKGROUND: Beef cattle breeding programs in Brazil have placed greater emphasis on the genomic study of reproductive traits of males and females due to their economic importance. In this study, genome-wide associations were assessed for scrotal circumference at 210 d of age, scrotal circumference at 420 d of age, age at first calving, and age at second calving, in Canchim beef cattle. Data quality control was conducted resulting in 672,778 SNPs and 392 animals.

RESULTS: Associated SNPs were observed for scrotal circumference at 420 d of age (435 SNPs), followed by scrotal circumference at 210 d of age (12 SNPs), age at first calving (six SNPs), and age at second calving (four SNPs). We investigated whether significant SNPs were within genic or surrounding regions. Biological processes of genes were associated with immune system, multicellular organismal process, response to stimulus, apoptotic process, cellular component organization or biogenesis, biological adhesion, and reproduction.

CONCLUSIONS: Few associations were observed for scrotal circumference at 210 d of age, age at first calving, and age at second calving, reinforcing their polygenic inheritance and the complexity of understanding the genetic architecture of reproductive traits. Finding many associations for scrotal circumference at 420 d of age in various regions of the Canchim genome also reveals the difficulty of targeting specific candidate genes that could act on fertility; nonetheless, the high linkage disequilibrium between loci herein estimated could aid to overcome this issue. Therefore, all relevant information about genomic regions influencing reproductive traits may contribute to target candidate genes for further investigation of causal mutations and aid in future genomic studies in Canchim cattle to improve the breeding program.}, } @article {pmid28846170, year = {2017}, author = {Votaw, HR and Ostrowski, EA}, title = {Stalk size and altruism investment within and among populations of the social amoeba.}, journal = {Journal of evolutionary biology}, volume = {30}, number = {11}, pages = {2017-2030}, doi = {10.1111/jeb.13172}, pmid = {28846170}, issn = {1420-9101}, mesh = {Altruism ; Dictyostelium/*cytology/genetics/*physiology ; Epistasis, Genetic ; Genotype ; Reproduction ; }, abstract = {Reproductive division of labour is common in many societies, including those of eusocial insects, cooperatively breeding vertebrates, and most forms of multicellularity. However, conflict over what is best for the individual vs. the group can prevent an optimal division of labour from being achieved. In the social amoeba Dictyostelium discoideum, cells aggregate to become multicellular and a fraction behaves altruistically, forming a dead stalk that supports the rest. Theory suggests that intra-organismal conflict over spore-stalk cell fate can drive rapid evolutionary change in allocation traits, leading to polymorphisms within populations or rapid divergence between them. Here, we assess several proxies for stalk size and spore-stalk allocation as metrics of altruism investment among strains and across geographic regions. We observe geographic divergence in stalk height that can be partly explained by differences in multicellular size, as well as variation among strains in clonal spore-stalk allocation, suggesting within-population variation in altruism investment. Analyses of chimeras comprised of strains from the same vs. different populations indicated genotype-by-genotype epistasis, where the morphology of the chimeras deviated significantly from the average morphology of the strains developed clonally. The significantly negative epistasis observed for allopatric pairings suggests that populations are diverging in their spore-stalk allocation behaviours, generating incompatibilities when they encounter one another. Our results demonstrate divergence in microbial social traits across geographically separated populations and demonstrate how quantification of genotype-by-genotype interactions can elucidate the trajectory of social trait evolution in nature.}, } @article {pmid28839913, year = {2017}, author = {Shapiro, JA}, title = {Biological action in Read-Write genome evolution.}, journal = {Interface focus}, volume = {7}, number = {5}, pages = {20160115}, pmid = {28839913}, issn = {2042-8898}, abstract = {Many of the most important evolutionary variations that generated phenotypic adaptations and originated novel taxa resulted from complex cellular activities affecting genome content and expression. These activities included (i) the symbiogenetic cell merger that produced the mitochondrion-bearing ancestor of all extant eukaryotes, (ii) symbiogenetic cell mergers that produced chloroplast-bearing ancestors of photosynthetic eukaryotes, and (iii) interspecific hybridizations and genome doublings that generated new species and adaptive radiations of higher plants and animals. Adaptive variations also involved horizontal DNA transfers and natural genetic engineering by mobile DNA elements to rewire regulatory networks, such as those essential to viviparous reproduction in mammals. In the most highly evolved multicellular organisms, biological complexity scales with 'non-coding' DNA content rather than with protein-coding capacity in the genome. Coincidentally, 'non-coding' RNAs rich in repetitive mobile DNA sequences function as key regulators of complex adaptive phenotypes, such as stem cell pluripotency. The intersections of cell fusion activities, horizontal DNA transfers and natural genetic engineering of Read-Write genomes provide a rich molecular and biological foundation for understanding how ecological disruptions can stimulate productive, often abrupt, evolutionary transformations.}, } @article {pmid28839200, year = {2017}, author = {Fickentscher, R and Weiss, M}, title = {Physical determinants of asymmetric cell divisions in the early development of Caenorhabditis elegans.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {9369}, pmid = {28839200}, issn = {2045-2322}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; *Asymmetric Cell Division ; Biomarkers ; Caenorhabditis elegans/*embryology ; Cell Size ; *Embryonic Development ; Gastrulation ; Germ Cells ; Models, Biological ; Spindle Apparatus/metabolism ; }, abstract = {Asymmetric cell divisions are of fundamental importance for the development of multicellular organisms, e.g. for the generation of founder cells. Prime examples are asymmetric cell divisions in germline precursors during the early embryogenesis of the transparent roundworm Caenorhabditis elegans, one of the major developmental model organisms. However, due to a lack of quantitative data it has remained unclear how frequent unequal daughter cell sizes emerge in the worm's early embryogenesis, and whether these originate from sterical or biochemical cues. Using quantitative light-sheet microscopy, we have found that about 40% of all cell divisions in C. elegans until gastrulation generate daughter cells with significantly different volumes. Removing the embryo's rigid eggshell revealed asymmetric divisions in somatic cells to be primarily induced by steric effects. Division asymmetries in the germline remained unaltered and were correctly reproduced by a model based on a cell-size independent, eccentric displacement of the metaphase plate. Our data suggest that asymmetric cell divisions, imposed by physical determinants, are essential for establishing important cell-cell interactions that eventually fuel a successful embryogenesis.}, } @article {pmid28830343, year = {2017}, author = {Chen, IK and Velicer, GJ and Yu, YN}, title = {Divergence of functional effects among bacterial sRNA paralogs.}, journal = {BMC evolutionary biology}, volume = {17}, number = {1}, pages = {199}, pmid = {28830343}, issn = {1471-2148}, mesh = {Alleles ; Base Sequence ; Evolution, Molecular ; Gene Expression Regulation, Bacterial ; Myxococcus xanthus/*genetics/growth & development ; Phylogeny ; RNA, Bacterial/*genetics ; *Sequence Homology, Nucleic Acid ; }, abstract = {BACKGROUND: Non-coding small RNAs (sRNAs) regulate a variety of important biological processes across all life domains, including bacteria. However, little is known about the functional evolution of sRNAs in bacteria, which might occur via changes in sRNA structure and/or stability or changes in interactions between sRNAs and their associated regulatory networks, including target mRNAs. The sRNA Pxr functions as a developmental gatekeeper in the model cooperative bacterium Myxococcus xanthus. Specifically, Pxr prevents the initiation of fruiting body development when nutrients are abundant. Previous work has shown that Pxr appears to have a recent origin within a sub-clade of the myxobacteria, which allowed us to infer the most recent common ancestor of pxr and examine the divergence of Pxr since its origin.

RESULTS: To test for inter-specific divergence in functional effects, extant pxr homologs from several species and their inferred ancestor were introduced into an M. xanthus deletion mutant lacking pxr. Both the inferred ancestral pxr and all extant alleles from species containing only one copy of pxr were found to control development in M. xanthus in a qualitatively similar manner to the native M. xanthus allele. However, multiple paralogs present in Cystobacter species exhibited divergent effects, with two paralogs controlling M. xanthus development but two others failing to do so. These differences may have occurred through changes in gene expression caused by apparent structural differences in the sRNA variants encoded by these paralogs.

CONCLUSIONS: Taken together, our results suggest that Pxr plays a common fundamental role in developmental gene regulation across diverse species of myxobacteria but also that the functional effects of some Pxr variants may be evolving in some lineages.}, } @article {pmid28827358, year = {2017}, author = {Larsen, NB and Liberti, SE and Vogel, I and Jørgensen, SW and Hickson, ID and Mankouri, HW}, title = {Stalled replication forks generate a distinct mutational signature in yeast.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {36}, pages = {9665-9670}, pmid = {28827358}, issn = {1091-6490}, mesh = {DNA Replication/*genetics ; DNA, Fungal/genetics/metabolism ; DNA, Single-Stranded/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Escherichia coli/genetics/metabolism ; Escherichia coli Proteins/genetics/metabolism ; Exodeoxyribonucleases/genetics/metabolism ; Genes, Reporter ; Genetic Engineering ; Humans ; Models, Biological ; Mutagenesis ; Mutation ; Nuclear Proteins/genetics/metabolism ; RecQ Helicases/genetics/metabolism ; Recombinant Proteins/genetics/metabolism ; Recombinational DNA Repair ; Replication Origin ; Saccharomyces cerevisiae/*genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; }, abstract = {Proliferating cells acquire genome alterations during the act of DNA replication. This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associated genome rearrangements are poorly understood, largely due to methodological difficulties in analyzing specific replication forks in vivo. To provide an insight into this process, we analyzed the mutagenic consequences of replication fork stalling at a single, site-specific replication barrier (the Escherichia coli Tus/Ter complex) engineered into the yeast genome. We demonstrate that transient stalling at this barrier induces a distinct pattern of genome rearrangements in the newly replicated region behind the stalled fork, which primarily consist of localized losses and duplications of DNA sequences. These genetic alterations arise through the aberrant repair of a single-stranded DNA gap, in a process that is dependent on Exo1- and Shu1-dependent homologous recombination repair (HRR). Furthermore, aberrant processing of HRR intermediates, and elevated HRR-associated mutagenesis, is detectable in a yeast model of the human cancer predisposition disorder, Bloom's syndrome. Our data reveal a mechanism by which cellular responses to stalled replication forks can actively generate genomic alterations and genetic diversity in normal proliferating cells.}, } @article {pmid28825126, year = {2018}, author = {Chi, S and Liu, T and Wang, X and Wang, R and Wang, S and Wang, G and Shan, G and Liu, C}, title = {Functional genomics analysis reveals the biosynthesis pathways of important cellular components (alginate and fucoidan) of Saccharina.}, journal = {Current genetics}, volume = {64}, number = {1}, pages = {259-273}, pmid = {28825126}, issn = {1432-0983}, support = {41376143//National Natural Science Foundation of China/ ; 14-2-4-104-jch//Qingdao applied basic research project/ ; }, mesh = {Alginates/*metabolism ; *Biosynthetic Pathways/genetics ; Computational Biology/methods ; Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Transfer, Horizontal ; *Genome ; *Genomics/methods ; Glucuronic Acid/metabolism ; Hexuronic Acids/metabolism ; High-Throughput Nucleotide Sequencing ; Phaeophyta/classification/*genetics/*metabolism ; Phylogeny ; Polysaccharides/*metabolism ; Symbiosis/genetics ; Transcriptome ; }, abstract = {Although alginate and fucoidan are unique cellular components and have important biological significance in brown algae, and many possible involved genes are present in brown algal genomes, their functions and regulatory mechanisms have not been fully revealed. Both polysaccharides may play important roles in the evolution of multicellular brown algae, but specific and in-depth studies are still limited. In this study, a functional genomics analysis of alginate and fucoidan biosynthesis routes was conducted in Saccharina, and the key events in these pathways in brown algae were identified. First, genes from different sources, including eukaryotic hosts via endosymbiotic gene transfer and bacteria via horizontal gene transfer, were combined to build a complete pathway framework. Then, a critical event occurred to drive these pathways to have real function: one of the mannose-6-phosphate isomerase homologs that arose by gene duplication subsequently adopted the function of the mannose-1-phosphate guanylyltransferase (MGP) gene, which was absent in algal genomes. Further, downstream pathway genes proceeded with gene expansions and complex transcriptional mechanisms, which may be conducive to the synthesis of alginate and fucoidan with diverse structures and contents depending on the developmental stage, tissue structure, and environmental conditions. This study revealed the alginate and fucoidan synthesis pathways and all included genes from separate phylogenetic sources in brown algae. Enzyme assays confirmed the function of key genes and led to the determination of a substitute for the missing MPG. All gene families had constitutively expressed member(s) to maintain the basic synthesis; and the gene function differentiation, enzyme characterization and gene expression regulation differences separated brown algae from other algae lineages and were considered to be the major driving forces for sophisticated system evolution of brown algae.}, } @article {pmid28820125, year = {2017}, author = {Stajich, JE}, title = {Fungal Genomes and Insights into the Evolution of the Kingdom.}, journal = {Microbiology spectrum}, volume = {5}, number = {4}, pages = {}, pmid = {28820125}, issn = {2165-0497}, support = {S10 OD016290/OD/NIH HHS/United States ; }, mesh = {Evolution, Molecular ; Fungi/*genetics ; Genes, Fungal/*genetics ; Genome, Fungal/*genetics ; }, abstract = {The kingdom Fungi comprises species that inhabit nearly all ecosystems. Fungi exist as both free-living and symbiotic unicellular and multicellular organisms with diverse morphologies. The genomes of fungi encode genes that enable them to thrive in diverse environments, invade plant and animal cells, and participate in nutrient cycling in terrestrial and aquatic ecosystems. The continuously expanding databases of fungal genome sequences have been generated by individual and large-scale efforts such as Génolevures, Broad Institute's Fungal Genome Initiative, and the 1000 Fungal Genomes Project (http://1000.fungalgenomes.org). These efforts have produced a catalog of fungal genes and genomic organization. The genomic datasets can be utilized to better understand how fungi have adapted to their lifestyles and ecological niches. Large datasets of fungal genomic and transcriptomic data have enabled the use of novel methodologies and improved the study of fungal evolution from a molecular sequence perspective. Combined with microscopes, petri dishes, and woodland forays, genome sequencing supports bioinformatics and comparative genomics approaches as important tools in the study of the biology and evolution of fungi.}, } @article {pmid28820115, year = {2017}, author = {Nagy, LG and Tóth, R and Kiss, E and Slot, J and Gácser, A and Kovács, GM}, title = {Six Key Traits of Fungi: Their Evolutionary Origins and Genetic Bases.}, journal = {Microbiology spectrum}, volume = {5}, number = {4}, pages = {}, doi = {10.1128/microbiolspec.FUNK-0036-2016}, pmid = {28820115}, issn = {2165-0497}, mesh = {*Biological Evolution ; Cell Lineage/genetics ; Evolution, Molecular ; Fruiting Bodies, Fungal/*growth & development ; Fungi/*genetics/*growth & development ; Hyphae/*growth & development ; Mycorrhizae/physiology ; Phylogeny ; Plants/microbiology ; }, abstract = {The fungal lineage is one of the three large eukaryotic lineages that dominate terrestrial ecosystems. They share a common ancestor with animals in the eukaryotic supergroup Opisthokonta and have a deeper common ancestry with plants, yet several phenotypes, such as morphological, physiological, or nutritional traits, make them unique among all living organisms. This article provides an overview of some of the most important fungal traits, how they evolve, and what major genes and gene families contribute to their development. The traits highlighted here represent just a sample of the characteristics that have evolved in fungi, including polarized multicellular growth, fruiting body development, dimorphism, secondary metabolism, wood decay, and mycorrhizae. However, a great number of other important traits also underlie the evolution of the taxonomically and phenotypically hyperdiverse fungal kingdom, which could fill up a volume on its own. After reviewing the evolution of these six well-studied traits in fungi, we discuss how the recurrent evolution of phenotypic similarity, that is, convergent evolution in the broad sense, has shaped their phylogenetic distribution in extant species.}, } @article {pmid28819830, year = {2017}, author = {Liu, A and He, F and Gu, X}, title = {Identification and characterization of tyrosine kinases in anole lizard indicate the conserved tyrosine kinase repertoire in vertebrates.}, journal = {Molecular genetics and genomics : MGG}, volume = {292}, number = {6}, pages = {1405-1418}, pmid = {28819830}, issn = {1617-4623}, mesh = {Amino Acid Sequence ; Animals ; Conserved Sequence ; Lizards/classification/genetics/*metabolism ; Phylogeny ; Protein-Tyrosine Kinases/chemistry/*genetics ; }, abstract = {The tyrosine kinases (TKs) play principal roles in regulation of multicellular aspects of the organism and are implicated in many cancer types and congenital disorders. The anole lizard has recently been introduced as a model organism for laboratory-based studies of organismal function and field studies of ecology and evolution. However, the TK family of anole lizard has not been systematically identified and characterized yet. In this study, we identified 82 TK-encoding genes in the anole lizard genome and classified them into 28 subfamilies through phylogenetic analysis, with no member from ROS and STYK1 subfamilies identified. Although TK domain sequences and domain organization in each subfamily were conserved, the total number of TKs in different species was much variable. In addition, extensive evolutionary analysis in metazoans indicated that TK repertoire in vertebrates tends to be remarkably stable. Phylogenetic analysis of Eph subfamily indicated that the divergence of EphA and EphB occurred prior to the whole genome duplication (WGD) but after the split of Urochordates and vertebrates. Moreover, the expression pattern analysis of lizard TK genes among 9 different tissues showed that 14 TK genes exhibited tissue-specific expression and 6 TK genes were widely expressed. Comparative analysis of TK expression suggested that the tissue specifically expressed genes showed different expression pattern but the widely expressed genes showed similar pattern between anole lizard and human. These results may provide insights into the evolutionary diversification of animal TK genes and would aid future studies on TK protein regulation of key growth and developmental processes.}, } @article {pmid28812655, year = {2017}, author = {Griffith, OW and Wagner, GP}, title = {The placenta as a model for understanding the origin and evolution of vertebrate organs.}, journal = {Nature ecology & evolution}, volume = {1}, number = {4}, pages = {72}, doi = {10.1038/s41559-017-0072}, pmid = {28812655}, issn = {2397-334X}, abstract = {How organs originate and evolve is a question fundamental to understanding the evolution of complex multicellular life forms. Vertebrates have a relatively standard body plan with more or less the same conserved set of organs. The placenta is a comparatively more recently evolved organ, derived in many lineages independently. Using placentas as a model, we discuss the genetic basis for organ origins. We show that the evolution of placentas occurs by acquiring new functional attributes to existing tissues, changes in the patterning and development of tissues, and the evolution of novel cell types. We argue that a diversity of genomic changes facilitated these physiological transformations and that these changes are likely to have occurred during the evolution of organs more broadly. Finally, we argue that a key aspect to understanding the evolutionary origin of organs is that they are likely to result from novel interactions between distinct cell populations.}, } @article {pmid28812251, year = {2017}, author = {Pavlovich, E and Volkova, N and Yakymchuk, E and Perepelitsyna, O and Sydorenko, M and Goltsev, A}, title = {In Vitro Study of Influence of Au Nanoparticles on HT29 and SPEV Cell Lines.}, journal = {Nanoscale research letters}, volume = {12}, number = {1}, pages = {494}, pmid = {28812251}, issn = {1931-7573}, abstract = {Cell culture models are excellent tools for potential toxicity of nanoparticles and fundamental investigations in cancer research. Thus, information about AuNP potential toxicity and effects on human health is necessary for the use of nanomaterials in clinical settings. The aim of our research is to examine the effects of AuNPs on the epithelial origin cell lines: continuous and oncogenic. Embryonic porcine kidney epithelial inoculated (SPEV) cell line and colorectal carcinoma cell line (HT29) were used. In the test cultures, the cell proliferation, necrosis/apoptosis, and multicellular spheroids generation were evaluated. We demonstrated that AuNP concentrations of 6-12 μg/ml reduced the proliferation of SPEV and HT29 cells and increased the cell number at early and late stages of apoptosis and necrosis. It was shown that small concentrations of AuNPs (1-3 μg/ml) stimulate multicellular spheroid formation by HT29 and SPEV cells. However, higher AuNP concentrations (6-12 μg/ml) had both cytotoxic and anti-cohesive effects on cell in suspension. The large sensitiveness to the action of AuNPs was shown by the line of HT29 (6 μg/ml) as compared to the SPEV cells (12 μg/ml). This experimental study of the effect of AuNPs on SPEV and HT29 cell lines will justify their further application in AuNP-mediated anticancer treatment.}, } @article {pmid28804953, year = {2017}, author = {Gyoja, F}, title = {Basic helix-loop-helix transcription factors in evolution: Roles in development of mesoderm and neural tissues.}, journal = {Genesis (New York, N.Y. : 2000)}, volume = {55}, number = {9}, pages = {}, doi = {10.1002/dvg.23051}, pmid = {28804953}, issn = {1526-968X}, mesh = {Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/chemistry/*genetics/metabolism ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Mesoderm/growth & development/*metabolism ; Nervous System/growth & development/*metabolism ; }, abstract = {Basic helix-loop-helix (bHLH) transcription factors have attracted the attention of developmental and evolutionary biologists for decades because of their conserved functions in mesodermal and neural tissue formation in both vertebrates and fruit flies. Their evolutionary history is of special interest because it will likely provide insights into developmental processes and refinement of metazoan-specific traits. This review briefly considers advances in developmental biological studies on bHLHs/HLHs. I also discuss recent genome-wide surveys and molecular phylogenetic analyses of these factors in a wide range of metazoans. I hypothesize that interactions between metazoan-specific Group A, D, and E bHLH/HLH factors enabled a sophisticated transition system from cell proliferation to differentiation in multicellular development. This control mechanism probably emerged initially to organize a multicellular animal body and was subsequently recruited to form evolutionarily novel tissues, which differentiated during a later ontogenetic phase.}, } @article {pmid28802203, year = {2017}, author = {Campbell, S and Aswad, A and Katzourakis, A}, title = {Disentangling the origins of virophages and polintons.}, journal = {Current opinion in virology}, volume = {25}, number = {}, pages = {59-65}, doi = {10.1016/j.coviro.2017.07.011}, pmid = {28802203}, issn = {1879-6265}, mesh = {DNA Transposable Elements/*genetics ; DNA, Viral/genetics ; Eukaryota/*virology ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Genome, Viral ; Giant Viruses/*genetics/physiology ; Phylogeny ; Virophages/*genetics ; Virus Diseases/genetics/transmission ; }, abstract = {Virophages and polintons are part of a complex system that also involves eukaryotes, giant viruses, as well as other viruses and transposable elements. Virophages are cosmopolitan, being found in environments ranging from the Amazon River to Antarctic hypersaline lakes, while polintons are found in many single celled and multicellular eukaryotes. Virophages and polintons have a shared ancestry, but their exact origins are unknown and obscured by antiquity and extensive horizontal gene transfer (HGT). Paleovirology can help disentangle the complicated gene flow between these two, as well as their giant viral and eukaryotic hosts. We outline the evidence and theoretical support for polintons being descended from viruses and not vice versa. In order to disentangle the natural history of polintons and virophages, we suggest that there is much to be gained by embracing rigorous metagenomics and evolutionary analyses. Methods from paleovirology will play a pivotal role in unravelling ancient relationships, HGT and patterns of cross-species transmission.}, } @article {pmid28798739, year = {2017}, author = {Song, H and Liu, J and Song, Q and Zhang, Q and Tian, P and Nan, Z}, title = {Comprehensive Analysis of Codon Usage Bias in Seven Epichloë Species and Their Peramine-Coding Genes.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1419}, pmid = {28798739}, issn = {1664-302X}, abstract = {Codon usage bias plays an important role in shaping genomes and genes in unicellular species and multicellular species. Here, we first analyzed codon usage bias in seven Epichloë species and their peramine-coding genes. Our results showed that both natural selection and mutation pressure played a role in forming codon usage bias in seven Epichloë species. All seven Epichloë species contained a peramine-coding gene cluster. Interestingly, codon usage bias of peramine-coding genes were not affected by natural selection or mutation pressure. There were 13 codons more frequently found in Epichloë genome sequences, peramine-coding gene clusters and orthologous peramine-coding genes, all of which had a bias to end with a C nucleotide. In the seven genomes analyzed, codon usage was biased in highly expressed coding sequences (CDSs) with shorter length and higher GC content. Genes in the peramine-coding gene cluster had higher GC content at the third nucleotide position of the codon, and highly expressed genes had higher GC content at the second position. In orthologous peramine-coding CDSs, high expression level was not significantly correlated with CDS length and GC content. Analysis of selection pressure identified that the genes orthologous to peramine genes were under purifying selection. There were no differences in codon usage bias and selection pressure between peramine product genes and non-functional peramine product genes. Our results provide insights into understanding codon evolution in Epichloë species.}, } @article {pmid28798731, year = {2017}, author = {Ibáñez de Aldecoa, AL and Zafra, O and González-Pastor, JE}, title = {Mechanisms and Regulation of Extracellular DNA Release and Its Biological Roles in Microbial Communities.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1390}, pmid = {28798731}, issn = {1664-302X}, abstract = {The capacity to release genetic material into the extracellular medium has been reported in cultures of numerous species of bacteria, archaea, and fungi, and also in the context of multicellular microbial communities such as biofilms. Moreover, extracellular DNA (eDNA) of microbial origin is widespread in natural aquatic and terrestrial environments. Different specific mechanisms are involved in eDNA release, such as autolysis and active secretion, as well as through its association with membrane vesicles. It is noteworthy that in microorganisms, in which DNA release has been studied in detail, the production of eDNA is coordinated by the population when it reaches a certain cell density, and is induced in a subpopulation in response to the accumulation of quorum sensing signals. Interestingly, in several bacteria there is also a relationship between eDNA release and the development of natural competence (the ability to take up DNA from the environment), which is also controlled by quorum sensing. Then, what is the biological function of eDNA? A common biological role has not been proposed, since different functions have been reported depending on the microorganism. However, it seems to be important in biofilm formation, can be used as a nutrient source, and could be involved in DNA damage repair and gene transfer. This review covers several aspects of eDNA research: (i) its occurrence and distribution in natural environments, (ii) the mechanisms and regulation of its release in cultured microorganisms, and (iii) its biological roles. In addition, we propose that eDNA release could be considered a social behavior, based on its quorum sensing-dependent regulation and on the described functions of eDNA in the context of microbial communities.}, } @article {pmid28786729, year = {2017}, author = {Gerlee, P and Basanta, D and Anderson, ARA}, title = {The Influence of Cellular Characteristics on the Evolution of Shape Homeostasis.}, journal = {Artificial life}, volume = {23}, number = {3}, pages = {424-448}, doi = {10.1162/ARTL_a_00240}, pmid = {28786729}, issn = {1064-5462}, mesh = {Cell Death/*physiology ; Cell Movement/*physiology ; Cell Polarity/*physiology ; *Homeostasis ; Intercellular Signaling Peptides and Proteins ; Models, Biological ; }, abstract = {The importance of individual cells in a developing multicellular organism is well known, but precisely how the individual cellular characteristics of those cells collectively drive the emergence of robust, homeostatic structures is less well understood. For example, cell communication via a diffusible factor allows for information to travel across large distances within the population, and cell polarization makes it possible to form structures with a particular orientation, but how do these processes interact to produce a more robust and regulated structure? In this study we investigate the ability of cells with different cellular characteristics to grow and maintain homeostatic structures. We do this in the context of an individual-based model where cell behavior is driven by an intracellular network that determines the cell phenotype. More precisely, we investigated evolution with 96 different permutations of our model, where cell motility, cell death, long-range growth factor (LGF), short-range growth factor (SGF), and cell polarization were either present or absent. The results show that LGF has the largest positive influence on the fitness of the evolved solutions. SGF and polarization also contribute, but all other capabilities essentially increase the search space, effectively making it more difficult to achieve a solution. By perturbing the evolved solutions, we found that they are highly robust to both mutations and wounding. In addition, we observed that by evolving solutions in more unstable environments they produce structures that were more robust and adaptive. In conclusion, our results suggest that robust collective behavior is most likely to evolve when cells are endowed with long-range communication, cell polarisation, and selection pressure from an unstable environment.}, } @article {pmid28774341, year = {2017}, author = {Riffle, S and Hegde, RS}, title = {Modeling tumor cell adaptations to hypoxia in multicellular tumor spheroids.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {36}, number = {1}, pages = {102}, pmid = {28774341}, issn = {1756-9966}, support = {R01 CA207068/CA/NCI NIH HHS/United States ; }, mesh = {Cell Line, Tumor ; Cell Proliferation/*drug effects ; Humans ; Spheroids, Cellular/*metabolism ; }, abstract = {Under hypoxic conditions, tumor cells undergo a series of adaptations that promote evolution of a more aggressive tumor phenotype including the activation of DNA damage repair proteins, altered metabolism, and decreased proliferation. Together these changes mitigate the negative impact of oxygen deprivation and allow preservation of genomic integrity and proliferative capacity, thus contributing to tumor growth and metastasis. As a result the presence of a hypoxic microenvironment is considered a negative clinical feature of many solid tumors. Hypoxic niches in tumors also represent a therapeutically privileged environment in which chemo- and radiation therapy is less effective. Although the negative impact of tumor hypoxia has been well established, the precise effect of oxygen deprivation on tumor cell behavior, and the molecular signals that allow a tumor cell to survive in vivo are poorly understood. Multicellular tumor spheroids (MCTS) have been used as an in vitro model for the avascular tumor niche, capable of more accurately recreating tumor genomic profiles and predicting therapeutic response. However, relatively few studies have used MCTS to study the molecular mechanisms driving tumor cell adaptations within the hypoxic tumor environment. Here we will review what is known about cell proliferation, DNA damage repair, and metabolic pathways as modeled in MCTS in comparison to observations made in solid tumors. A more precise definition of the cell populations present within 3D tumor models in vitro could better inform our understanding of the heterogeneity within tumors as well as provide a more representative platform for the testing of therapeutic strategies.}, } @article {pmid28768887, year = {2017}, author = {Tong, K and Wang, Y and Su, Z}, title = {Phosphotyrosine signalling and the origin of animal multicellularity.}, journal = {Proceedings. Biological sciences}, volume = {284}, number = {1860}, pages = {}, pmid = {28768887}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; *Cell Communication ; Eukaryota/enzymology/*genetics ; Phosphotyrosine/*metabolism ; Protein-Tyrosine Kinases/*metabolism ; *Signal Transduction ; }, abstract = {The evolution of multicellular animals (i.e. metazoans) from a unicellular ancestor is one of the most important yet least understood evolutionary transitions. Historically, given its indispensable functions in intercellular communication and exclusive presence in metazoans, phosphotyrosine (pTyr) signalling was considered a metazoan-specific evolutionary innovation that might have contributed to the origin of metazoan multicellularity. However, recent studies have led to a new understanding of pTyr signalling evolution and its role in the metazoan origin. Sequence analyses have unravelled a much earlier emergence of pTyr signalling in eukaryotic evolution. Even so, several distinct properties of holozoan pTyr signalling may have paved the way for a hypothesized functional transition of pTyr signalling at the multicellular origin, from environmental sensing to intercellular communication, and for it to evolve as a powerful intercellular signalling system for multicellularity. Biochemical analyses of premetazoan pTyr signalling components have further revealed the premetazoan origin of many key features of metazoan pTyr signalling, and the metazoan establishment of others, including the Csk-mediated negative regulation of the activity of Src, a conserved tyrosine kinase in the Holozoa. Finally, potential future directions are discussed, with a stress on the biological functions of premetazoan pTyr signalling via newly developed gene manipulation tools in non-animal holozoans.}, } @article {pmid28762573, year = {2017}, author = {Zanchi, C and Johnston, PR and Rolff, J}, title = {Evolution of defence cocktails: Antimicrobial peptide combinations reduce mortality and persistent infection.}, journal = {Molecular ecology}, volume = {26}, number = {19}, pages = {5334-5343}, doi = {10.1111/mec.14267}, pmid = {28762573}, issn = {1365-294X}, mesh = {Animals ; Bacterial Load ; Gene Knockdown Techniques ; Host-Pathogen Interactions ; *Immunity, Innate ; Insect Proteins/genetics/*immunology ; RNA Interference ; Staphylococcal Infections/*immunology ; Staphylococcus aureus ; Tenebrio/*immunology ; }, abstract = {The simultaneous expression of costly immune effectors such as multiple antimicrobial peptides is a hallmark of innate immunity of multicellular organisms, yet the adaptive advantage remains unresolved. Here, we test current hypotheses on the evolution of such defence cocktails. We use RNAi gene knock-down to explore, the effects of three highly expressed antimicrobial peptides, displaying different degrees of activity in vitro against Staphylococcus aureus, during an infection in the beetle Tenebrio molitor. We find that a defensin confers no survival benefit but reduces bacterial loads. A coleoptericin contributes to host survival without affecting bacterial loads. An attacin has no individual effect. Simultaneous knock-down of the defensin with the other AMPs results in increased mortality and elevated bacterial loads. Contrary to common expectations, the effects on host survival and bacterial load can be independent. The expression of multiple AMPs increases host survival and contributes to the control of persisting infections and tolerance. This is an emerging property that explains the adaptive benefit of defence cocktails.}, } @article {pmid28761011, year = {2017}, author = {Borges, RM}, title = {Co-niche construction between hosts and symbionts: ideas and evidence.}, journal = {Journal of genetics}, volume = {96}, number = {3}, pages = {483-489}, pmid = {28761011}, issn = {0973-7731}, mesh = {Animals ; Biological Evolution ; *Ecosystem ; Gene Transfer, Horizontal ; Genome/genetics ; Host Specificity/*genetics ; *Inheritance Patterns ; Phenotype ; Symbiosis/*genetics ; }, abstract = {Symbiosis is a process that can generate evolutionary novelties and can extend the phenotypic niche space of organisms. Symbionts can act together with their hosts to co-construct host organs, within which symbionts are housed. Once established within hosts, symbionts can also influence various aspects of host phenotype, such as resource acquisition, protection from predation by acquisition of toxicity, as well as behaviour. Once symbiosis is established, its fidelity between generations must be ensured. Hosts evolve various mechanisms to screen unwanted symbionts and to facilitate faithful transmission of mutualistic partners between generations. Microbes are the most important symbionts that have influenced plant and animal phenotypes; multicellular organisms engage in developmental symbioses with microbes at many stages in ontogeny. The co-construction of niches may result in composite organisms that are physically nested within each other. While it has been advocated that these composite organisms need new evolutionary theories and perspectives to describe their properties and evolutionary trajectories, it appears that standard evolutionary theories are adequate to explore selection pressures on their composite or individual traits. Recent advances in our understanding of composite organisms open up many important questions regarding the stability and transmission of these units.}, } @article {pmid28755343, year = {2017}, author = {Abdelbar, OH}, title = {Histological Analysis of the Developmental Stages of Direct Somatic Embryogenesis Induced from In Vitro Leaf Explants of Date Palm.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1637}, number = {}, pages = {145-162}, doi = {10.1007/978-1-4939-7156-5_13}, pmid = {28755343}, issn = {1940-6029}, mesh = {Culture Media/chemistry ; Germination ; In Vitro Techniques ; Inflorescence/*cytology ; Phoeniceae/cytology/*growth & development ; Plant Leaves/growth & development ; Plant Somatic Embryogenesis Techniques/*methods ; Regeneration ; Seeds/growth & development ; }, abstract = {Somatic embryogenesis is an ideal technique for the micropropagation of date palm using different explant tissue; however, histological studies describing the ontogenesis of plant regeneration are limited. This chapter provides a simple protocol for the histological analysis of the successive developmental stages of direct somatic embryogenesis induced from in vitro leaf explants. Direct somatic embryos are obtained from Murashige and Skoog (MS) medium containing 2 mg/L 6-benzylaminopurine. In order to observe the different developmental stages, histological analysis is carried out on samples at 15-day intervals for 60 days. Samples are fixed in formalin acetic alcohol and embedded in paraffin wax. Stain serial transverse and longitudinal sections, 8 μm thick, are stained with safranin-Fast Green. After 15 days on the induction medium, somatic embryos exhibit multicellular origin directly from the procambium cells, whereas the mesophyll and the epidermal cells are not involved in this process. After 2 months, several developmental stages (pre-globular, globular, early bipolar, bipolar, and cotyledonary-shaped) are observed. These embryos germinate after transferring to MS medium without plant growth regulators and rooting on 2 mg/L NAA-containing medium resulting in complete plantlets.}, } @article {pmid28749982, year = {2017}, author = {Yoshida, Y and Koutsovoulos, G and Laetsch, DR and Stevens, L and Kumar, S and Horikawa, DD and Ishino, K and Komine, S and Kunieda, T and Tomita, M and Blaxter, M and Arakawa, K}, title = {Comparative genomics of the tardigrades Hypsibius dujardini and Ramazzottius varieornatus.}, journal = {PLoS biology}, volume = {15}, number = {7}, pages = {e2002266}, pmid = {28749982}, issn = {1545-7885}, mesh = {Animals ; Base Sequence ; Chromosome Mapping/veterinary ; DNA/chemistry/metabolism ; Desiccation ; Extremophiles/*genetics/growth & development/physiology ; Gene Expression Profiling/veterinary ; *Gene Expression Regulation ; Gene Transfer, Horizontal ; Genetic Linkage ; Genome Size ; Genome-Wide Association Study/veterinary ; Genomic Library ; High-Throughput Nucleotide Sequencing/veterinary ; Multigene Family ; Phylogeny ; Proteome/genetics/*metabolism ; Reproducibility of Results ; Species Specificity ; Tardigrada/*genetics/growth & development/physiology ; }, abstract = {Tardigrada, a phylum of meiofaunal organisms, have been at the center of discussions of the evolution of Metazoa, the biology of survival in extreme environments, and the role of horizontal gene transfer in animal evolution. Tardigrada are placed as sisters to Arthropoda and Onychophora (velvet worms) in the superphylum Panarthropoda by morphological analyses, but many molecular phylogenies fail to recover this relationship. This tension between molecular and morphological understanding may be very revealing of the mode and patterns of evolution of major groups. Limnoterrestrial tardigrades display extreme cryptobiotic abilities, including anhydrobiosis and cryobiosis, as do bdelloid rotifers, nematodes, and other animals of the water film. These extremophile behaviors challenge understanding of normal, aqueous physiology: how does a multicellular organism avoid lethal cellular collapse in the absence of liquid water? Meiofaunal species have been reported to have elevated levels of horizontal gene transfer (HGT) events, but how important this is in evolution, and particularly in the evolution of extremophile physiology, is unclear. To address these questions, we resequenced and reassembled the genome of H. dujardini, a limnoterrestrial tardigrade that can undergo anhydrobiosis only after extensive pre-exposure to drying conditions, and compared it to the genome of R. varieornatus, a related species with tolerance to rapid desiccation. The 2 species had contrasting gene expression responses to anhydrobiosis, with major transcriptional change in H. dujardini but limited regulation in R. varieornatus. We identified few horizontally transferred genes, but some of these were shown to be involved in entry into anhydrobiosis. Whole-genome molecular phylogenies supported a Tardigrada+Nematoda relationship over Tardigrada+Arthropoda, but rare genomic changes tended to support Tardigrada+Arthropoda.}, } @article {pmid28745003, year = {2018}, author = {Müller, V and de Boer, RJ and Bonhoeffer, S and Szathmáry, E}, title = {An evolutionary perspective on the systems of adaptive immunity.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {505-528}, doi = {10.1111/brv.12355}, pmid = {28745003}, issn = {1469-185X}, mesh = {Adaptive Immunity/*genetics ; Animals ; *Biological Evolution ; Genetic Fitness ; Vertebrates/*genetics/*immunology ; }, abstract = {We propose an evolutionary perspective to classify and characterize the diverse systems of adaptive immunity that have been discovered across all major domains of life. We put forward a new function-based classification according to the way information is acquired by the immune systems: Darwinian immunity (currently known from, but not necessarily limited to, vertebrates) relies on the Darwinian process of clonal selection to 'learn' by cumulative trial-and-error feedback; Lamarckian immunity uses templated targeting (guided adaptation) to internalize heritable information on potential threats; finally, shotgun immunity operates through somatic mechanisms of variable targeting without feedback. We argue that the origin of Darwinian (but not Lamarckian or shotgun) immunity represents a radical innovation in the evolution of individuality and complexity, and propose to add it to the list of major evolutionary transitions. While transitions to higher-level units entail the suppression of selection at lower levels, Darwinian immunity re-opens cell-level selection within the multicellular organism, under the control of mechanisms that direct, rather than suppress, cell-level evolution for the benefit of the individual. From a conceptual point of view, the origin of Darwinian immunity can be regarded as the most radical transition in the history of life, in which evolution by natural selection has literally re-invented itself. Furthermore, the combination of clonal selection and somatic receptor diversity enabled a transition from limited to practically unlimited capacity to store information about the antigenic environment. The origin of Darwinian immunity therefore comprises both a transition in individuality and the emergence of a new information system - the two hallmarks of major evolutionary transitions. Finally, we present an evolutionary scenario for the origin of Darwinian immunity in vertebrates. We propose a revival of the concept of the 'Big Bang' of vertebrate immunity, arguing that its origin involved a 'difficult' (i.e. low-probability) evolutionary transition that might have occurred only once, in a common ancestor of all vertebrates. In contrast to the original concept, we argue that the limiting innovation was not the generation of somatic diversity, but the regulatory circuitry needed for the safe operation of amplifiable immune responses with somatically acquired targeting. Regulatory complexity increased abruptly by genomic duplications at the root of the vertebrate lineage, creating a rare opportunity to establish such circuitry. We discuss the selection forces that might have acted at the origin of the transition, and in the subsequent stepwise evolution leading to the modern immune systems of extant vertebrates.}, } @article {pmid28741966, year = {2017}, author = {Bryja, V and Červenka, I and Čajánek, L}, title = {The connections of Wnt pathway components with cell cycle and centrosome: side effects or a hidden logic?.}, journal = {Critical reviews in biochemistry and molecular biology}, volume = {52}, number = {6}, pages = {614-637}, pmid = {28741966}, issn = {1549-7798}, support = {166533/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Animals ; Cell Communication ; *Cell Cycle ; Cell Polarity ; Centrosome/*metabolism ; Humans ; *Wnt Signaling Pathway ; }, abstract = {Wnt signaling cascade has developed together with multicellularity to orchestrate the development and homeostasis of complex structures. Wnt pathway components - such as β-catenin, Dishevelled (DVL), Lrp6, and Axin-- are often dedicated proteins that emerged in evolution together with the Wnt signaling cascade and are believed to function primarily in the Wnt cascade. It is interesting to see that in recent literature many of these proteins are connected with cellular functions that are more ancient and not limited to multicellular organisms - such as cell cycle regulation, centrosome biology, or cell division. In this review, we summarize the recent literature describing this crosstalk. Specifically, we attempt to find the answers to the following questions: Is the response to Wnt ligands regulated by the cell cycle? Is the centrosome and/or cilium required to activate the Wnt pathway? How do Wnt pathway components regulate the centrosomal cycle and cilia formation and function? We critically review the evidence that describes how these connections are regulated and how they help to integrate cell-to-cell communication with the cell and the centrosomal cycle in order to achieve a fine-tuned, physiological response.}, } @article {pmid28736221, year = {2017}, author = {Paris, M and Götz, A and Hettrich, I and Bidan, CM and Dunlop, JWC and Razi, H and Zizak, I and Hutmacher, DW and Fratzl, P and Duda, GN and Wagermaier, W and Cipitria, A}, title = {Scaffold curvature-mediated novel biomineralization process originates a continuous soft tissue-to-bone interface.}, journal = {Acta biomaterialia}, volume = {60}, number = {}, pages = {64-80}, doi = {10.1016/j.actbio.2017.07.029}, pmid = {28736221}, issn = {1878-7568}, mesh = {Animals ; *Calcification, Physiologic ; Cartilage/*metabolism/pathology ; *Osteogenesis ; Sheep ; *Stress, Mechanical ; Tissue Scaffolds/*chemistry ; }, abstract = {UNLABELLED: A myriad of shapes are found in biological tissues, often naturally evolved to fulfill a particular function. In the field of tissue engineering, substrate geometry influences cell behavior and tissue formation in vitro, yet little is known how this translates to an in vivo scenario. Here we investigate scaffold curvature-induced tissue growth, without additional growth factors or cells, in an ovine animal model. We show that soft tissue formation follows a curvature-driven tissue growth model. The highly organized endogenous soft matrix, potentially under mechanical strain, leads to a non-standard form of biomineralization, whereby the pre-existing organic matrix is mineralized without collagen remodeling and without an intermediate cartilage ossification phase. Micro- and nanoscale characterization of the tissue microstructure using histology, backscattered electron (BSE) and second-harmonic generation (SHG) imaging and synchrotron small angle X-ray scattering (SAXS) revealed (i) continuous collagen fibers across the soft-hard tissue interface on the tip of mineralized cones, and (ii) bone remodeling by basic multicellular units (BMUs) in regions adjacent to the native cortical bone. Thus, features of soft tissue-to-bone interface resembling the insertion sites of ligaments and tendons into bone were created, using a scaffold that did not mimic the structural or biological gradients across such a complex interface at its mature state. This study provides fundamental knowledge for biomimetic scaffold design in the fields of bone regeneration and soft tissue-to-bone interface tissue engineering.

STATEMENT OF SIGNIFICANCE: Geometry influences cell behavior and tissue formation in vitro. However, little is known how this translates to an in vivo scenario. Here we investigate the influence of scaffold mean surface curvature on in vivo tissue growth using an ovine animal model. Based on a multiscale tissue microstructure characterization, we show a seamless integration of soft tissue into newly formed bone, resembling the insertion sites of ligaments and tendons into bone. This interface was created using a scaffold without additional growth factors or cells that did not recapitulate the structural or biological gradients across such a complex tissue interface at its mature state. These findings have important implications for biomimetic scaffold design for bone regeneration and soft tissue-to-bone interface tissue engineering.}, } @article {pmid28729688, year = {2017}, author = {Stepanauskas, R and Fergusson, EA and Brown, J and Poulton, NJ and Tupper, B and Labonté, JM and Becraft, ED and Brown, JM and Pachiadaki, MG and Povilaitis, T and Thompson, BP and Mascena, CJ and Bellows, WK and Lubys, A}, title = {Improved genome recovery and integrated cell-size analyses of individual uncultured microbial cells and viral particles.}, journal = {Nature communications}, volume = {8}, number = {1}, pages = {84}, pmid = {28729688}, issn = {2041-1723}, mesh = {Base Composition ; Cell Size ; Deinococcus/cytology/*genetics ; Escherichia coli/cytology/*genetics ; Flow Cytometry ; Genome, Bacterial/*genetics ; Genome, Viral/*genetics ; Nucleic Acid Amplification Techniques ; Prochlorococcus/cytology/*genetics ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Single-Cell Analysis ; Virion/*genetics ; }, abstract = {Microbial single-cell genomics can be used to provide insights into the metabolic potential, interactions, and evolution of uncultured microorganisms. Here we present WGA-X, a method based on multiple displacement amplification of DNA that utilizes a thermostable mutant of the phi29 polymerase. WGA-X enhances genome recovery from individual microbial cells and viral particles while maintaining ease of use and scalability. The greatest improvements are observed when amplifying high G+C content templates, such as those belonging to the predominant bacteria in agricultural soils. By integrating WGA-X with calibrated index-cell sorting and high-throughput genomic sequencing, we are able to analyze genomic sequences and cell sizes of hundreds of individual, uncultured bacteria, archaea, protists, and viral particles, obtained directly from marine and soil samples, in a single experiment. This approach may find diverse applications in microbiology and in biomedical and forensic studies of humans and other multicellular organisms.Single-cell genomics can be used to study uncultured microorganisms. Here, Stepanauskas et al. present a method combining improved multiple displacement amplification and FACS, to obtain genomic sequences and cell size information from uncultivated microbial cells and viral particles in environmental samples.}, } @article {pmid28726632, year = {2017}, author = {Grau-Bové, X and Torruella, G and Donachie, S and Suga, H and Leonard, G and Richards, TA and Ruiz-Trillo, I}, title = {Dynamics of genomic innovation in the unicellular ancestry of animals.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {28726632}, issn = {2050-084X}, support = {616960/ERC_/European Research Council/International ; }, mesh = {Eukaryota/*genetics ; *Evolution, Molecular ; *Genome, Protozoan ; Genomics ; }, abstract = {Which genomic innovations underpinned the origin of multicellular animals is still an open debate. Here, we investigate this question by reconstructing the genome architecture and gene family diversity of ancestral premetazoans, aiming to date the emergence of animal-like traits. Our comparative analysis involves genomes from animals and their closest unicellular relatives (the Holozoa), including four new genomes: three Ichthyosporea and Corallochytrium limacisporum. Here, we show that the earliest animals were shaped by dynamic changes in genome architecture before the emergence of multicellularity: an early burst of gene diversity in the ancestor of Holozoa, enriched in transcription factors and cell adhesion machinery, was followed by multiple and differently-timed episodes of synteny disruption, intron gain and genome expansions. Thus, the foundations of animal genome architecture were laid before the origin of complex multicellularity - highlighting the necessity of a unicellular perspective to understand early animal evolution.}, } @article {pmid28719054, year = {2018}, author = {Plattner, H}, title = {Evolutionary Cell Biology of Proteins from Protists to Humans and Plants.}, journal = {The Journal of eukaryotic microbiology}, volume = {65}, number = {2}, pages = {255-289}, doi = {10.1111/jeu.12449}, pmid = {28719054}, issn = {1550-7408}, mesh = {*Biological Evolution ; *Cell Biology ; Eukaryotic Cells/*metabolism ; *Genetic Variation ; Phylogeny ; Plastids/genetics ; }, abstract = {During evolution, the cell as a fine-tuned machine had to undergo permanent adjustments to match changes in its environment, while "closed for repair work" was not possible. Evolution from protists (protozoa and unicellular algae) to multicellular organisms may have occurred in basically two lineages, Unikonta and Bikonta, culminating in mammals and angiosperms (flowering plants), respectively. Unicellular models for unikont evolution are myxamoebae (Dictyostelium) and increasingly also choanoflagellates, whereas for bikonts, ciliates are preferred models. Information accumulating from combined molecular database search and experimental verification allows new insights into evolutionary diversification and maintenance of genes/proteins from protozoa on, eventually with orthologs in bacteria. However, proteins have rarely been followed up systematically for maintenance or change of function or intracellular localization, acquirement of new domains, partial deletion (e.g. of subunits), and refunctionalization, etc. These aspects are discussed in this review, envisaging "evolutionary cell biology." Protozoan heritage is found for most important cellular structures and functions up to humans and flowering plants. Examples discussed include refunctionalization of voltage-dependent Ca[2+] channels in cilia and replacement by other types during evolution. Altogether components serving Ca[2+] signaling are very flexible throughout evolution, calmodulin being a most conservative example, in contrast to calcineurin whose catalytic subunit is lost in plants, whereas both subunits are maintained up to mammals for complex functions (immune defense and learning). Domain structure of R-type SNAREs differs in mono- and bikonta, as do Ca[2+] -dependent protein kinases. Unprecedented selective expansion of the subunit a which connects multimeric base piece and head parts (V0, V1) of H[+] -ATPase/pump may well reflect the intriguing vesicle trafficking system in ciliates, specifically in Paramecium. One of the most flexible proteins is centrin when its intracellular localization and function throughout evolution is traced. There are many more examples documenting evolutionary flexibility of translation products depending on requirements and potential for implantation within the actual cellular context at different levels of evolution. From estimates of gene and protein numbers per organism, it appears that much of the basic inventory of protozoan precursors could be transmitted to highest eukaryotic levels, with some losses and also with important additional "inventions."}, } @article {pmid28716924, year = {2017}, author = {Brawley, SH and Blouin, NA and Ficko-Blean, E and Wheeler, GL and Lohr, M and Goodson, HV and Jenkins, JW and Blaby-Haas, CE and Helliwell, KE and Chan, CX and Marriage, TN and Bhattacharya, D and Klein, AS and Badis, Y and Brodie, J and Cao, Y and Collén, J and Dittami, SM and Gachon, CMM and Green, BR and Karpowicz, SJ and Kim, JW and Kudahl, UJ and Lin, S and Michel, G and Mittag, M and Olson, BJSC and Pangilinan, JL and Peng, Y and Qiu, H and Shu, S and Singer, JT and Smith, AG and Sprecher, BN and Wagner, V and Wang, W and Wang, ZY and Yan, J and Yarish, C and Zäuner-Riek, S and Zhuang, Y and Zou, Y and Lindquist, EA and Grimwood, J and Barry, KW and Rokhsar, DS and Schmutz, J and Stiller, JW and Grossman, AR and Prochnik, SE}, title = {Insights into the red algae and eukaryotic evolution from the genome of Porphyra umbilicalis (Bangiophyceae, Rhodophyta).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {31}, pages = {E6361-E6370}, pmid = {28716924}, issn = {1091-6490}, support = {P20 GM103418/GM/NIGMS NIH HHS/United States ; P20 GM103638/GM/NIGMS NIH HHS/United States ; BB/1013164/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Actins/genetics ; Calcium Signaling/genetics ; Cell Cycle/genetics ; Cell Wall/genetics/metabolism ; Chromatin/genetics ; Cytoskeleton/*genetics ; *Evolution, Molecular ; Genome, Plant/*genetics ; Kinesins/genetics ; Phylogeny ; Porphyra/*cytology/*genetics ; }, abstract = {Porphyra umbilicalis (laver) belongs to an ancient group of red algae (Bangiophyceae), is harvested for human food, and thrives in the harsh conditions of the upper intertidal zone. Here we present the 87.7-Mbp haploid Porphyra genome (65.8% G + C content, 13,125 gene loci) and elucidate traits that inform our understanding of the biology of red algae as one of the few multicellular eukaryotic lineages. Novel features of the Porphyra genome shared by other red algae relate to the cytoskeleton, calcium signaling, the cell cycle, and stress-tolerance mechanisms including photoprotection. Cytoskeletal motor proteins in Porphyra are restricted to a small set of kinesins that appear to be the only universal cytoskeletal motors within the red algae. Dynein motors are absent, and most red algae, including Porphyra, lack myosin. This surprisingly minimal cytoskeleton offers a potential explanation for why red algal cells and multicellular structures are more limited in size than in most multicellular lineages. Additional discoveries further relating to the stress tolerance of bangiophytes include ancestral enzymes for sulfation of the hydrophilic galactan-rich cell wall, evidence for mannan synthesis that originated before the divergence of green and red algae, and a high capacity for nutrient uptake. Our analyses provide a comprehensive understanding of the red algae, which are both commercially important and have played a major role in the evolution of other algal groups through secondary endosymbioses.}, } @article {pmid28714591, year = {2017}, author = {Kloesener, MH and Bose, J and Schulte, RD}, title = {Experimental evolution with a multicellular host causes diversification within and between microbial parasite populations-Differences in emerging phenotypes of two different parasite strains.}, journal = {Evolution; international journal of organic evolution}, volume = {71}, number = {9}, pages = {2194-2205}, doi = {10.1111/evo.13306}, pmid = {28714591}, issn = {1558-5646}, mesh = {Animals ; *Bacillus thuringiensis ; Biological Evolution ; Caenorhabditis elegans/parasitology ; Genotype ; *Host-Parasite Interactions ; Parasites ; Phenotype ; Selection, Genetic ; }, abstract = {Host-parasite coevolution is predicted to have complex evolutionary consequences, potentially leading to the emergence of genetic and phenotypic diversity for both antagonists. However, little is known about variation in phenotypic responses to coevolution between different parasite strains exposed to the same experimental conditions. We infected Caenorhabditis elegans with one of two strains of Bacillus thuringiensis and either allowed the host and the parasite to experimentally coevolve (coevolution treatment) or allowed only the parasite to adapt to the host (one-sided parasite adaptation). By isolating single parasite clones from evolved populations, we found phenotypic diversification of the ancestral strain into distinct clones, which varied in virulence toward ancestral hosts and competitive ability against other parasite genotypes. Parasite phenotypes differed remarkably not only between the two strains, but also between and within different replicate populations, indicating diversification of the clonal population caused by selection. This study highlights that the evolutionary selection pressure mediated by a multicellular host causes phenotypic diversification, but not necessarily with the same phenotypic outcome for different parasite strains.}, } @article {pmid28713421, year = {2017}, author = {Mohanta, TK and Bae, H}, title = {Analyses of Genomic tRNA Reveal Presence of Novel tRNAs in Oryza sativa.}, journal = {Frontiers in genetics}, volume = {8}, number = {}, pages = {90}, pmid = {28713421}, issn = {1664-8021}, abstract = {Transfer rRNAs are important molecules responsible for the translation event during protein synthesis. tRNAs are widespread found in unicellular to multi-cellular organisms. Analysis of tRNA gene family members in Oryza sativa revealed the presence of 750 tRNA genes distributed unevenly in different chromosomes. The length of O. sativa tRNAs genes were ranged from 66 to 91 nucleotides encoding 52 isoacceptor in total. tRNA[Ser] found in chromosome 8 of O. sativa encoded only 66 nucleotides which is the smallest tRNA of O. sativa and to our knowledge, this is the smallest gene of eukaryotic lineage reported so far. Analyses revealed the presence of several novel/pseudo tRNA genes in O. sativa which are reported for the first time. Multiple sequence alignment of tRNAs revealed the presence of family specific conserved consensus sequences. Functional study of these novel tRNA and family specific conserved consensus sequences will be crucial to decipher their importance in biological events. The rate of transition of O. sativa tRNA was found to be higher than the rate of transversion. Evolutionary study revealed, O. sativa tRNAs were evolved from the lineages of multiple common ancestors. Duplication and loss study of tRNAs genes revealed, majority of the O. sativa tRNA were duplicated and 17 of them were found to be undergone loss during the evolution. Orthology and paralogy study showed, the majority of O. sativa tRNA were paralogous and only a few of tRNA[Ser] were found to contain orthologous tRNAs.}, } @article {pmid28713189, year = {2017}, author = {Keijzer, F and Arnellos, A}, title = {The animal sensorimotor organization: a challenge for the environmental complexity thesis.}, journal = {Biology & philosophy}, volume = {32}, number = {3}, pages = {421-441}, pmid = {28713189}, issn = {0169-3867}, abstract = {Godfrey-Smith's environmental complexity thesis (ECT) is most often applied to multicellular animals and the complexity of their macroscopic environments to explain how cognition evolved. We think that the ECT may be less suited to explain the origins of the animal bodily organization, including this organization's potentiality for dealing with complex macroscopic environments. We argue that acquiring the fundamental sensorimotor features of the animal body may be better explained as a consequence of dealing with internal bodily-rather than environmental complexity. To press and elucidate this option, we develop the notion of an animal sensorimotor organization (ASMO) that derives from an internal coordination account for the evolution of early nervous systems. The ASMO notion is a reply to the question how a collection of single cells can become integrated such that the resulting multicellular organization becomes sensitive to and can manipulate macroscopic features of both the animal body and its environment. In this account, epithelial contractile tissues play the central role in the organization behind complex animal bodies. In this paper, we relate the ASMO concept to recent work on epithelia, which provides empirical evidence that supports central assumptions behind the ASMO notion. Second, we discuss to what extent the notion applies to basic animal architectures, exemplified by sponges and jellyfish. We conclude that the features exhibited by the ASMO are plausibly explained by internal constraints acting on and within this multicellular organization, providing a challenge for the role the ECT plays in this context.}, } @article {pmid28711427, year = {2017}, author = {Hinnant, TD and Alvarez, AA and Ables, ET}, title = {Temporal remodeling of the cell cycle accompanies differentiation in the Drosophila germline.}, journal = {Developmental biology}, volume = {429}, number = {1}, pages = {118-131}, pmid = {28711427}, issn = {1095-564X}, support = {R15 GM117502/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biomarkers/metabolism ; *Cell Cycle/genetics ; *Cell Differentiation/genetics ; Cell Proliferation/genetics ; Cell Self Renewal/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*cytology/genetics ; Female ; Fluorescence ; Genes, Reporter ; Germ Cells/*cytology ; Mitosis/genetics ; Morphogenesis/genetics ; Ovary/cytology ; Proteolysis ; Stem Cells/cytology/metabolism ; Time Factors ; Ubiquitin/metabolism ; Up-Regulation/genetics ; }, abstract = {Development of multicellular organisms relies upon the coordinated regulation of cellular differentiation and proliferation. Growing evidence suggests that some molecular regulatory pathways associated with the cell cycle machinery also dictate cell fate; however, it remains largely unclear how the cell cycle is remodeled in concert with cell differentiation. During Drosophila oogenesis, mature oocytes are created through a series of precisely controlled division and differentiation steps, originating from a single tissue-specific stem cell. Further, germline stem cells (GSCs) and their differentiating progeny remain in a predominantly linear arrangement as oogenesis proceeds. The ability to visualize the stepwise events of differentiation within the context of a single tissue make the Drosophila ovary an exceptional model for study of cell cycle remodeling. To describe how the cell cycle is remodeled in germ cells as they differentiate in situ, we used the Drosophila Fluorescence Ubiquitin-based Cell Cycle Indicator (Fly-FUCCI) system, in which degradable versions of GFP::E2f1 and RFP::CycB fluorescently label cells in each phase of the cell cycle. We found that the lengths of the G1, S, and G2 phases of the cell cycle change dramatically over the course of differentiation, and identified the 4/8-cell cyst as a key developmental transition state in which cells prepare for specialized cell cycles. Our data suggest that the transcriptional activator E2f1, which controls the transition from G1 to S phase, is a key regulator of mitotic divisions in the early germline. Our data support the model that E2f1 is necessary for proper GSC proliferation, self-renewal, and daughter cell development. In contrast, while E2f1 degradation by the Cullin 4 (Cul4)-containing ubiquitin E3 ligase (CRL4) is essential for developmental transitions in the early germline, our data do not support a role for E2f1 degradation as a mechanism to limit GSC proliferation or self-renewal. Taken together, these findings provide further insight into the regulation of cell proliferation and the acquisition of differentiated cell fate, with broad implications across developing tissues.}, } @article {pmid28709942, year = {2017}, author = {Leslie, MP and Shelton, DE and Michod, RE}, title = {Generation time and fitness tradeoffs during the evolution of multicellularity.}, journal = {Journal of theoretical biology}, volume = {430}, number = {}, pages = {92-102}, doi = {10.1016/j.jtbi.2017.07.007}, pmid = {28709942}, issn = {1095-8541}, mesh = {*Adaptation, Physiological ; *Biological Evolution ; Cell Differentiation ; Cell Survival ; Fertility ; *Genetic Fitness ; Models, Biological ; Time Factors ; }, abstract = {The evolution of multicellular organisms from their unicellular ancestors is an example of an evolutionary transition in individuality (ETI), i.e. a change in the units of selection and adaptation. The theory of ETIs poses particular challenges because, by definition, key theoretical constructs such as fitness are shifting during an ETI. Past work emphasized the importance of life history tradeoffs during ETIs in which lower level units form groups and become individuals at a higher level. In particular, it has been hypothesized that the convexity of the lower-level tradeoff between viability and fecundity changes with group size and determines the optimality of lower-level specialization in the fitness components of the group. This is important because lower-level specialization is a key indicator of higher-level individuality. Here we show that increasing generation time can increase the convexity of the lower-level viability-fecundity tradeoff. This effect is a novel hypothesis for the positive association between cell-group size and cellular specialization in a major model system for ETIs, the volvocine algae. The pattern in this clade is thought to be an example of a more general size-complexity rule. Our hypothesis is that larger groups have longer generation times and longer generation times lead to more convex lower-level viability-fecundity tradeoffs, which could account for specialization being optimal only in larger cell groups (colonies). We discuss the robustness of this effect to various changes in the assumptions of our model. Our work is important for the study of ETIs in general because viability and fecundity are fundamental components of fitness in all systems and because generation time is expected to be changing during many ETIs.}, } @article {pmid28704372, year = {2017}, author = {Trail, F and Wang, Z and Stefanko, K and Cubba, C and Townsend, JP}, title = {The ancestral levels of transcription and the evolution of sexual phenotypes in filamentous fungi.}, journal = {PLoS genetics}, volume = {13}, number = {7}, pages = {e1006867}, pmid = {28704372}, issn = {1553-7404}, mesh = {Bayes Theorem ; *Biological Evolution ; Fruiting Bodies, Fungal/genetics ; Fungi/genetics ; Gene Expression Regulation, Fungal/genetics ; Gene Knockout Techniques ; Genome, Fungal/*genetics ; Neurospora crassa/genetics ; Phenotype ; Phylogeny ; Sex Differentiation/*genetics ; Sordariales/genetics/growth & development ; Transcriptome/*genetics ; }, abstract = {Changes in gene expression have been hypothesized to play an important role in the evolution of divergent morphologies. To test this hypothesis in a model system, we examined differences in fruiting body morphology of five filamentous fungi in the Sordariomycetes, culturing them in a common garden environment and profiling genome-wide gene expression at five developmental stages. We reconstructed ancestral gene expression phenotypes, identifying genes with the largest evolved increases in gene expression across development. Conducting knockouts and performing phenotypic analysis in two divergent species typically demonstrated altered fruiting body development in the species that had evolved increased expression. Our evolutionary approach to finding relevant genes proved far more efficient than other gene deletion studies targeting whole genomes or gene families. Combining gene expression measurements with knockout phenotypes facilitated the refinement of Bayesian networks of the genes underlying fruiting body development, regulation of which is one of the least understood processes of multicellular development.}, } @article {pmid28700638, year = {2017}, author = {Ashrafi, S and Helaly, S and Schroers, HJ and Stadler, M and Richert-Poeggeler, KR and Dababat, AA and Maier, W}, title = {Ijuhya vitellina sp. nov., a novel source for chaetoglobosin A, is a destructive parasite of the cereal cyst nematode Heterodera filipjevi.}, journal = {PloS one}, volume = {12}, number = {7}, pages = {e0180032}, pmid = {28700638}, issn = {1932-6203}, mesh = {Animals ; Hyphae/growth & development ; Hypocreales/classification/genetics/metabolism/*pathogenicity ; Indole Alkaloids/*metabolism ; Oocytes/microbiology ; Phylogeny ; Tylenchoidea/growth & development/microbiology ; }, abstract = {Cyst nematodes are globally important pathogens in agriculture. Their sedentary lifestyle and long-term association with the roots of host plants render cyst nematodes especially good targets for attack by parasitic fungi. In this context fungi were specifically isolated from nematode eggs of the cereal cyst nematode Heterodera filipjevi. Here, Ijuhya vitellina (Ascomycota, Hypocreales, Bionectriaceae), encountered in wheat fields in Turkey, is newly described on the basis of phylogenetic analyses, morphological characters and life-style related inferences. The species destructively parasitises eggs inside cysts of H. filipjevi. The parasitism was reproduced in in vitro studies. Infected eggs were found to harbour microsclerotia produced by I. vitellina that resemble long-term survival structures also known from other ascomycetes. Microsclerotia were also formed by this species in pure cultures obtained from both, solitarily isolated infected eggs obtained from fields and artificially infected eggs. Hyphae penetrating the eggshell colonised the interior of eggs and became transformed into multicellular, chlamydospore-like structures that developed into microsclerotia. When isolated on artificial media, microsclerotia germinated to produce multiple emerging hyphae. The specific nature of morphological structures produced by I. vitellina inside nematode eggs is interpreted as a unique mode of interaction allowing long-term survival of the fungus inside nematode cysts that are known to survive periods of drought or other harsh environmental conditions. Generic classification of the new species is based on molecular phylogenetic inferences using five different gene regions. I. vitellina is the only species of the genus known to parasitise nematodes and produce microsclerotia. Metabolomic analyses revealed that within the Ijuhya species studied here, only I. vitellina produces chaetoglobosin A and its derivate 19-O-acetylchaetoglobosin A. Nematicidal and nematode-inhibiting activities of these compounds have been demonstrated suggesting that the production of these compounds may represent an adaptation to nematode parasitism.}, } @article {pmid28687715, year = {2017}, author = {Goelzer, A and Fromion, V}, title = {Resource allocation in living organisms.}, journal = {Biochemical Society transactions}, volume = {45}, number = {4}, pages = {945-952}, doi = {10.1042/BST20160436}, pmid = {28687715}, issn = {1470-8752}, mesh = {Animals ; Calibration ; *Energy Metabolism ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; *Genome ; Genomics/methods/trends ; Humans ; *Models, Biological ; Species Specificity ; Systems Biology/methods/trends ; Validation Studies as Topic ; }, abstract = {Quantitative prediction of resource allocation for living systems has been an intensive area of research in the field of biology. Resource allocation was initially investigated in higher organisms by using empirical mathematical models based on mass distribution. A challenge is now to go a step further by reconciling the cellular scale to the individual scale. In the present paper, we review the foundations of modelling of resource allocation, particularly at the cellular scale: from small macro-molecular models to genome-scale cellular models. We enlighten how the combination of omic measurements and computational advances together with systems biology has contributed to dramatic progresses in the current understanding and prediction of cellular resource allocation. Accurate genome-wide predictive methods of resource allocation based on the resource balance analysis (RBA) framework have been developed and ensure a good trade-off between the complexity/tractability and the prediction capability of the model. The RBA framework shows promise for a wide range of applications in metabolic engineering and synthetic biology, and for pursuing investigations of the design principles of cellular and multi-cellular organisms.}, } @article {pmid28687624, year = {2018}, author = {Tejos, R and Rodriguez-Furlán, C and Adamowski, M and Sauer, M and Norambuena, L and Friml, J}, title = {PATELLINS are regulators of auxin-mediated PIN1 relocation and plant development in Arabidopsis thaliana.}, journal = {Journal of cell science}, volume = {131}, number = {2}, pages = {}, doi = {10.1242/jcs.204198}, pmid = {28687624}, issn = {1477-9137}, mesh = {Arabidopsis/drug effects/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Body Patterning/drug effects ; Gene Expression Regulation, Plant/drug effects ; Indoleacetic Acids/pharmacology ; Membrane Transport Proteins/genetics/*metabolism ; Mutation/genetics ; Phenotype ; Phylogeny ; *Plant Development/drug effects ; Plant Epidermis/cytology ; Plant Roots/drug effects/genetics/growth & development/metabolism ; Seedlings/drug effects/metabolism ; Seeds/drug effects/genetics ; }, abstract = {Coordinated cell polarization in developing tissues is a recurrent theme in multicellular organisms. In plants, a directional distribution of the plant hormone auxin is at the core of many developmental programs. A feedback regulation of auxin on the polarized localization of PIN auxin transporters in individual cells has been proposed as a self-organizing mechanism for coordinated tissue polarization, but the molecular mechanisms linking auxin signalling to PIN-dependent auxin transport remain unknown. We used a microarray-based approach to find regulators of the auxin-induced PIN relocation in Arabidopsis thaliana root, and identified a subset of a family of phosphatidylinositol transfer proteins (PITPs), the PATELLINs (PATLs). Here, we show that PATLs are expressed in partially overlapping cell types in different tissues going through mitosis or initiating differentiation programs. PATLs are plasma membrane-associated proteins accumulated in Arabidopsis embryos, primary roots, lateral root primordia and developing stomata. Higher order patl mutants display reduced PIN1 repolarization in response to auxin, shorter root apical meristem, and drastic defects in embryo and seedling development. This suggests that PATLs play a redundant and crucial role in polarity and patterning in Arabidopsis.}, } @article {pmid28683136, year = {2017}, author = {Ballinger, MJ and Perlman, SJ}, title = {Generality of toxins in defensive symbiosis: Ribosome-inactivating proteins and defense against parasitic wasps in Drosophila.}, journal = {PLoS pathogens}, volume = {13}, number = {7}, pages = {e1006431}, pmid = {28683136}, issn = {1553-7374}, mesh = {Animals ; Bacterial Proteins/genetics/metabolism/*toxicity ; Bacterial Toxins/genetics/metabolism/*toxicity ; Biological Evolution ; Drosophila/genetics/*microbiology/*parasitology/physiology ; Larva/genetics/microbiology/parasitology/physiology ; Ribosome Inactivating Proteins/genetics/metabolism/*toxicity ; Spiroplasma/genetics/*metabolism ; *Symbiosis ; Wasps/*drug effects/physiology ; }, abstract = {While it has become increasingly clear that multicellular organisms often harbor microbial symbionts that protect their hosts against natural enemies, the mechanistic underpinnings underlying most defensive symbioses are largely unknown. Spiroplasma bacteria are widespread associates of terrestrial arthropods, and include strains that protect diverse Drosophila flies against parasitic wasps and nematodes. Recent work implicated a ribosome-inactivating protein (RIP) encoded by Spiroplasma, and related to Shiga-like toxins in enterohemorrhagic Escherichia coli, in defense against a virulent parasitic nematode in the woodland fly, Drosophila neotestacea. Here we test the generality of RIP-mediated protection by examining whether Spiroplasma RIPs also play a role in wasp protection, in D. melanogaster and D. neotestacea. We find strong evidence for a major role of RIPs, with ribosomal RNA (rRNA) from the larval endoparasitic wasps, Leptopilina heterotoma and Leptopilina boulardi, exhibiting the hallmarks of RIP activity. In Spiroplasma-containing hosts, parasitic wasp ribosomes show abundant site-specific depurination in the α-sarcin/ricin loop of the 28S rRNA, with depurination occurring soon after wasp eggs hatch inside fly larvae. Interestingly, we found that the pupal ectoparasitic wasp, Pachycrepoideus vindemmiae, escapes protection by Spiroplasma, and its ribosomes do not show high levels of depurination. We also show that fly ribosomes show little evidence of targeting by RIPs. Finally, we find that the genome of D. neotestacea's defensive Spiroplasma encodes a diverse repertoire of RIP genes, which are differ in abundance. This work suggests that specificity of defensive symbionts against different natural enemies may be driven by the evolution of toxin repertoires, and that toxin diversity may play a role in shaping host-symbiont-enemy interactions.}, } @article {pmid28682226, year = {2017}, author = {El Kafsi, H and Gorochov, G and Larsen, M}, title = {[Not Available].}, journal = {Biologie aujourd'hui}, volume = {211}, number = {1}, pages = {39-49}, doi = {10.1051/jbio/2017010}, pmid = {28682226}, issn = {2105-0686}, mesh = {Animals ; Gastrointestinal Microbiome/*genetics/*immunology ; Host-Pathogen Interactions/genetics/immunology ; Humans ; Immune System/metabolism/*physiology ; Immunity, Cellular/physiology ; Immunity, Humoral/physiology ; Immunoglobulin A, Secretory/physiology ; Inheritance Patterns ; Symbiosis/*genetics/*immunology ; }, abstract = {Genetic evolution of multicellular organisms occurred as a response to environmental challenges, in particular competition for nutrients, climatic change, physical and chemical stressors and pathogens. However organism fitness depends on both the efficiency of its defences and its capacities for benefiting from its symbiotic organisms. Indeed microbes not only engender pathogenies, but enable efficient uptake of host non-self biodegradable nutriments. Furthermore, microbes play an important role in the development of host immunity. We shall review here the associations between some specific genes of the host, microbiota and the immune system. Recent genome-wide association studies disclose that symbiosis between host and microbiota results from a stringent genetic co-evolution. On the other hand, a microbe subset isolated from murine and human microbiotes has been identified on the basis of its interaction with both the host genetics and immunity. Remarkably, microbes which have two such connections are taxonomically related. The best performing bacterial genuses in these two perspectives are Bifidobacterium, Lactobacillus and Akkermansia. We conclude that future therapies targeting microbiota within the framework of chronic inflammatory diseases must consider together host immune and genetic characters associated with microbiota homeostasis.}, } @article {pmid28681487, year = {2017}, author = {Wloch-Salamon, DM and Fisher, RM and Regenberg, B}, title = {Division of labour in the yeast: Saccharomyces cerevisiae.}, journal = {Yeast (Chichester, England)}, volume = {34}, number = {10}, pages = {399-406}, doi = {10.1002/yea.3241}, pmid = {28681487}, issn = {1097-0061}, mesh = {Adaptation, Physiological ; Apoptosis ; Biofilms/growth & development ; Biological Evolution ; Phenotype ; Resting Phase, Cell Cycle ; Saccharomyces cerevisiae/genetics/*physiology ; }, abstract = {Division of labour between different specialized cell types is a central part of how we describe complexity in multicellular organisms. However, it is increasingly being recognized that division of labour also plays an important role in the lives of predominantly unicellular organisms. Saccharomyces cerevisiae displays several phenotypes that could be considered a division of labour, including quiescence, apoptosis and biofilm formation, but they have not been explicitly treated as such. We discuss each of these examples, using a definition of division of labour that involves phenotypic variation between cells within a population, cooperation between cells performing different tasks and maximization of the inclusive fitness of all cells involved. We then propose future research directions and possible experimental tests using S. cerevisiae as a model organism for understanding the genetic mechanisms and selective pressures that can lead to the evolution of the very first stages of a division of labour. Copyright © 2017 John Wiley & Sons, Ltd.}, } @article {pmid28680959, year = {2017}, author = {Adjiri, A}, title = {DNA Mutations May Not Be the Cause of Cancer.}, journal = {Oncology and therapy}, volume = {5}, number = {1}, pages = {85-101}, pmid = {28680959}, issn = {2366-1070}, abstract = {Cancer is the most challenging disease of our time with increasing numbers of new cases each year, worldwide. Great achievements have been reached in cancer research through deep sequencing which helped define druggable targets. However, the still-evolving targeted therapy suffers resistance suggesting that DNA mutations considered as drivers may not have a role in tumor initiation. The present work discusses the role of DNA mutations as drivers and passengers in cancer initiation and development. First, it is important to discern the role of these DNA mutations as initiating events causing cancer or as contributors crucial for the development of a tumor once it has initiated. Second, breast cancer shown here illustrates how identification of DNA mutations in cancerous cells has influenced our approach for anti-cancer drug design. The cancer trilogy we have reached and described as: initial drug; resistance/recurrence; drug/treatment combinations, calls for a paradigm shift. To design more effective cancer drugs with durable and positive outcome, future cancer research needs to move beyond the sequencing era and explore changes which are taking place in cancer cells at levels other than the DNA. Evolutionary constraints may be acting as a barrier to preserve the human species from being transformed and, for that matter, all multi-cellular species which can incur cancer. Furthermore, mutations in the DNA do occur and for a multitude of reasons but without necessarily causing cancer. New directions will draw themselves when more focus is given to the event responsible for the switch of a cell from normalcy to malignancy. Until then, targeted therapy will certainly continue to improve the outcome of patients; however, it is unlikely to eradicate breast cancer depicted here.}, } @article {pmid28679746, year = {2017}, author = {Lyons, NA and Kolter, R}, title = {Bacillus subtilis Protects Public Goods by Extending Kin Discrimination to Closely Related Species.}, journal = {mBio}, volume = {8}, number = {4}, pages = {}, pmid = {28679746}, issn = {2150-7511}, support = {R01 GM058213/GM/NIGMS NIH HHS/United States ; }, mesh = {*Antibiosis ; Bacillus/physiology ; Bacillus subtilis/*genetics/*physiology ; Bacterial Proteins/metabolism ; Biofilms ; Biological Evolution ; Biota ; Gene Expression Regulation, Bacterial ; Microbial Interactions ; Phenotype ; Phylogeny ; }, abstract = {Kin discrimination systems are found in numerous communal contexts like multicellularity and are theorized to prevent exploitation of cooperative behaviors. The kin discrimination system in Bacillus subtilis differs from most other such systems because it excludes nonkin cells rather than including kin cells. Because nonkin are the target of the system, B. subtilis can potentially distinguish degrees of nonkin relatedness, not just kin versus nonkin. We examined this by testing a large strain collection of diverse Bacillus species against B. subtilis in different multicellular contexts. The effects of kin discrimination extend to nearby species, as the other subtilis clade species were treated with the same antagonism as nonkin. Species in the less-related pumilus clade started to display varied phenotypes but were mostly still discriminated against, while cereus clade members and beyond were no longer subject to kin discrimination. Seeking a reason why other species are perceived as antagonistic nonkin, we tested the ability of B. subtilis to steal communally produced surfactant from these species. We found that the species treated as nonkin were the only ones that made a surfactant that B. subtilis could utilize and that nonkin antagonism prevented such stealing when the two strains were mixed. The nonkin exclusion kin discrimination method thus allows effective protection of the cooperative behaviors prevalent in multicellularity while still permitting interactions with more distant species that are not a threat.IMPORTANCE Multicellular systems like bacterial biofilms and swarms rely on cooperative behaviors that could be undermined by exploitative invaders. Discriminating kin from nonkin is one way to help guard against such exploitation but has thus far been examined only intraspecifically, so the phylogenetic range of this important trait is unknown. We tested whether Bacillus subtilis treats other species as nonkin by testing a single strain against a diverse collection of Bacillus isolates. We found that the species in the same clade were treated as nonkin, which then lessened in more distant relatives. Further experiments showed that these nonkin species produced a cooperative good that could be stolen by B. subtilis and that treating each other as nonkin largely prevented this exploitation. These results impact our understanding of interspecies interactions, as bacterial populations can interact only after they have diverged enough to no longer be a threat to their cooperative existences.}, } @article {pmid28673540, year = {2017}, author = {Song, Y and Botvinnik, OB and Lovci, MT and Kakaradov, B and Liu, P and Xu, JL and Yeo, GW}, title = {Single-Cell Alternative Splicing Analysis with Expedition Reveals Splicing Dynamics during Neuron Differentiation.}, journal = {Molecular cell}, volume = {67}, number = {1}, pages = {148-161.e5}, pmid = {28673540}, issn = {1097-4164}, support = {R01 AI095277/AI/NIAID NIH HHS/United States ; R01 AI123202/AI/NIAID NIH HHS/United States ; P30 NS047101/NS/NINDS NIH HHS/United States ; R01 HG004659/HG/NHGRI NIH HHS/United States ; U19 MH107367/MH/NIMH NIH HHS/United States ; R01 HD085902/HD/NICHD NIH HHS/United States ; R01 NS075449/NS/NINDS NIH HHS/United States ; }, mesh = {Algorithms ; *Alternative Splicing ; Bayes Theorem ; Cell Line ; Computer Simulation ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Humans ; Kinetics ; Male ; Models, Genetic ; Nerve Tissue Proteins/*biosynthesis/genetics ; Neural Stem Cells/*metabolism ; *Neurogenesis ; Neurons/*metabolism ; Phenotype ; Pluripotent Stem Cells/*metabolism ; RNA, Messenger/genetics/*metabolism ; *Single-Cell Analysis ; }, abstract = {Alternative splicing (AS) generates isoform diversity for cellular identity and homeostasis in multicellular life. Although AS variation has been observed among single cells, little is known about the biological or evolutionary significance of such variation. We developed Expedition, a computational framework consisting of outrigger, a de novo splice graph transversal algorithm to detect AS; anchor, a Bayesian approach to assign modalities; and bonvoyage, a visualization tool using non-negative matrix factorization to display modality changes. Applying Expedition to single pluripotent stem cells undergoing neuronal differentiation, we discover that up to 20% of AS exons exhibit bimodality. Bimodal exons are flanked by more conserved intronic sequences harboring distinct cis-regulatory motifs, constitute much of cell-type-specific splicing, are highly dynamic during cellular transitions, preserve reading frame, and reveal intricacy of cell states invisible to conventional gene expression analysis. Systematic AS characterization in single cells redefines our understanding of AS complexity in cell biology.}, } @article {pmid28669817, year = {2017}, author = {Timoshevskiy, VA and Lampman, RT and Hess, JE and Porter, LL and Smith, JJ}, title = {Deep ancestry of programmed genome rearrangement in lampreys.}, journal = {Developmental biology}, volume = {429}, number = {1}, pages = {31-34}, pmid = {28669817}, issn = {1095-564X}, support = {R01 GM104123/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA/metabolism ; Gene Rearrangement/*genetics ; *Genome ; Germ Cells/metabolism ; Lampreys/*genetics ; *Phylogeny ; }, abstract = {In most multicellular organisms, the structure and content of the genome is rigorously maintained over the course of development. However some species have evolved genome biologies that permit, or require, developmentally regulated changes in the physical structure and content of the genome (programmed genome rearrangement: PGR). Relatively few vertebrates are known to undergo PGR, although all agnathans surveyed to date (several hagfish and one lamprey: Petromyzon marinus) show evidence of large scale PGR. To further resolve the ancestry of PGR within vertebrates, we developed probes that allow simultaneous tracking of nearly all sequences eliminated by PGR in P. marinus and a second lamprey species (Entosphenus tridentatus). These comparative analyses reveal conserved subcellular structures (lagging chromatin and micronuclei) associated with PGR and provide the first comparative embryological evidence in support of the idea that PGR represents an ancient and evolutionarily stable strategy for regulating inherent developmental/genetic conflicts between germline and soma.}, } @article {pmid28663071, year = {2017}, author = {Rosa-Fernandes, L and Maselli, LMF and Maeda, NY and Palmisano, G and Bydlowski, SP}, title = {Outside-in, inside-out: Proteomic analysis of endothelial stress mediated by 7-ketocholesterol.}, journal = {Chemistry and physics of lipids}, volume = {207}, number = {Pt B}, pages = {231-238}, doi = {10.1016/j.chemphyslip.2017.06.008}, pmid = {28663071}, issn = {1873-2941}, mesh = {Cell Survival/drug effects ; Cells, Cultured ; Computational Biology ; Dose-Response Relationship, Drug ; Human Umbilical Vein Endothelial Cells/*drug effects ; Humans ; Ketocholesterols/*pharmacology ; Mass Spectrometry ; Oxidative Stress/*drug effects ; Platelet Aggregation/drug effects ; *Proteomics ; Structure-Activity Relationship ; }, abstract = {Oxysterols are cholesterol oxidation products formed through enzymatic or autoxidation mechanisms. 7-ketocholeterol (7KC) is one of most abundant oxysterols found in atherosclerotic lesions. Its role in atherosclerosis pathogenesis has been broadly studied in a variety of models. The arterial microenvironment is a multicellular dynamic compartment that, among other systemic factors, is continuously stimulated by 7KC. Endothelial cells have a key role on that environment, being in intimate contact with both the blood stream and the vessel wall, the site of disease origin. 7KC has been shown to promote endothelial cell death and/or dysfunction, depending on its concentration. However, its contribution to the cell microenvironment through cell stimulation has not received much attention. Here we applied mass spectrometry-based proteomics followed by bioinformatics workflow to analyze the effect of a non-toxic 7KC concentration on endothelial cell protein expression and secretion in vitro. Trypsin digests were prepared from the secretome of the endothelial cells and from the total cell pellet after 24h exposure to 7KC. All samples were analyzed by high resolution and accurate mass nano-LC MS/MS. After database search and statistical analysis, differentially expressed proteins were selected for further studies. Our workflow identified 1805 secreted proteins and 2203 intracellular proteins, and of these, 48 and 53, respectively, were regulated. Regulated proteins upon 7KC exposure are involved in unfolded protein response, vascular homeostasis, and reduced control of angiogenesis. Moreover, blood coagulation was another main pathway regulated through Tissue Factor Pathway Inhibitor (TFPI), an antithrombotic agent associated with coronary disease that we found to be more than 2 times downregulated. Taken together, these data show differential endothelial protein regulation and secretion upon 7KC exposure for short time periods under non-toxic conditions. Herewith, these data support the role of 7KC in atherosclerosis pathophysiology and thus reinforce the deleterious effect of endothelial cells stress in the arterial microenvironment.}, } @article {pmid28648822, year = {2017}, author = {Hehenberger, E and Tikhonenkov, DV and Kolisko, M and Del Campo, J and Esaulov, AS and Mylnikov, AP and Keeling, PJ}, title = {Novel Predators Reshape Holozoan Phylogeny and Reveal the Presence of a Two-Component Signaling System in the Ancestor of Animals.}, journal = {Current biology : CB}, volume = {27}, number = {13}, pages = {2043-2050.e6}, doi = {10.1016/j.cub.2017.06.006}, pmid = {28648822}, issn = {1879-0445}, mesh = {Animals ; *Biological Evolution ; Eukaryota/*classification/genetics/*physiology ; Evolution, Molecular ; Fetal Proteins/genetics/metabolism ; *Predatory Behavior ; RNA, Ribosomal, 18S/genetics ; *Signal Transduction ; T-Box Domain Proteins/genetics/metabolism ; }, abstract = {Our understanding of the origin of animals has been transformed by characterizing their most closely related, unicellular sisters: the choanoflagellates, filastereans, and ichthyosporeans. Together with animals, these lineages make up the Holozoa [1, 2]. Many traits previously considered "animal specific" were subsequently found in other holozoans [3, 4], showing that they evolved before animals, although exactly when is currently uncertain because several key relationships remain unresolved [2, 5]. Here we report the morphology and transcriptome sequencing from three novel unicellular holozoans: Pigoraptor vietnamica and Pigoraptor chileana, which are related to filastereans, and Syssomonas multiformis, which forms a new lineage with Corallochytrium in phylogenomic analyses. All three species are predatory flagellates that feed on large eukaryotic prey, and all three also appear to exhibit complex life histories with several distinct stages, including multicellular clusters. Examination of genes associated with multicellularity in animals showed that the new filastereans contain a cell-adhesion gene repertoire similar to those of other species in this group. Syssomonas multiformis possessed a smaller complement overall but does encode genes absent from the earlier-branching ichthyosporeans. Analysis of the T-box transcription factor domain showed expansion of T-box transcription factors based on combination with a non-T-box domain (a receiver domain), which has not been described outside of vertebrates. This domain and other domains we identified in all unicellular holozoans are part of the two-component signaling system that has been lost in animals, suggesting the continued use of this system in the closest relatives of animals and emphasizing the importance of studying loss of function as well as gain in major evolutionary transitions.}, } @article {pmid28644721, year = {2019}, author = {Rivero, C and Traubenik, S and Zanetti, ME and Blanco, FA}, title = {Small GTPases in plant biotic interactions.}, journal = {Small GTPases}, volume = {10}, number = {5}, pages = {350-360}, pmid = {28644721}, issn = {2154-1256}, mesh = {Biological Transport, Active/physiology ; Cell Membrane/*enzymology ; GTP Phosphohydrolases/*metabolism ; Plant Proteins/*metabolism ; Plants/*enzymology ; Signal Transduction/*physiology ; }, abstract = {The superfamily of small monomeric GTPases originated in a common ancestor of eukaryotic multicellular organisms and, since then, it has evolved independently in each lineage to cope with the environmental challenges imposed by their different life styles. Members of the small GTPase family function in the control of vesicle trafficking, cytoskeleton rearrangements and signaling during crucial biological processes, such as cell growth and responses to environmental cues. In this review, we discuss the emerging roles of these small GTPases in the pathogenic and symbiotic interactions established by plants with microorganisms present in their nearest environment, in which membrane trafficking is crucial along the different steps of the interaction, from recognition and signal transduction to nutrient exchange.}, } @article {pmid28637850, year = {2017}, author = {Heim, NA and Payne, JL and Finnegan, S and Knope, ML and Kowalewski, M and Lyons, SK and McShea, DW and Novack-Gottshall, PM and Smith, FA and Wang, SC}, title = {Hierarchical complexity and the size limits of life.}, journal = {Proceedings. Biological sciences}, volume = {284}, number = {1857}, pages = {}, pmid = {28637850}, issn = {1471-2954}, mesh = {*Biological Evolution ; Earth, Planet ; *Eukaryota ; *Prokaryotic Cells ; }, abstract = {Over the past 3.8 billion years, the maximum size of life has increased by approximately 18 orders of magnitude. Much of this increase is associated with two major evolutionary innovations: the evolution of eukaryotes from prokaryotic cells approximately 1.9 billion years ago (Ga), and multicellular life diversifying from unicellular ancestors approximately 0.6 Ga. However, the quantitative relationship between organismal size and structural complexity remains poorly documented. We assessed this relationship using a comprehensive dataset that includes organismal size and level of biological complexity for 11 172 extant genera. We find that the distributions of sizes within complexity levels are unimodal, whereas the aggregate distribution is multimodal. Moreover, both the mean size and the range of size occupied increases with each additional level of complexity. Increases in size range are non-symmetric: the maximum organismal size increases more than the minimum. The majority of the observed increase in organismal size over the history of life on the Earth is accounted for by two discrete jumps in complexity rather than evolutionary trends within levels of complexity. Our results provide quantitative support for an evolutionary expansion away from a minimal size constraint and suggest a fundamental rescaling of the constraints on minimal and maximal size as biological complexity increases.}, } @article {pmid28637420, year = {2017}, author = {Baig, AM and Rana, Z and Tariq, SS and Ahmad, HR}, title = {Bioinformatic Insights on Target Receptors of Amiodarone in Human and Acanthamoeba castellanii.}, journal = {Infectious disorders drug targets}, volume = {17}, number = {3}, pages = {160-177}, doi = {10.2174/1871526517666170622075154}, pmid = {28637420}, issn = {2212-3989}, mesh = {Acanthamoeba castellanii/chemistry/*drug effects/metabolism ; Amiodarone/*metabolism/*pharmacology ; Calcium Channels/*chemistry/genetics ; *Computational Biology ; Cytochrome P-450 CYP3A/*chemistry/genetics ; Humans ; Intramolecular Transferases/chemistry/genetics ; Ligands ; Models, Molecular ; Protein Binding ; Protozoan Proteins/*chemistry/metabolism ; Sequence Homology, Amino Acid ; Trypanosoma cruzi/chemistry/drug effects/genetics ; }, abstract = {BACKGROUND: Amiodarone is prescribed for certain cardiac arrhythmias in current medical practice. The drug targets and inhibits voltage dependent sodium (Na+ v), calcium (Ca+2 v), potassium (K+ v) channels, enzymes like cytochrome P450 and oxidosqualene cyclase. Past studies have shown that amiodarone exerts antiparasitic effects against Trypanosoma cruzi and Acanthamoeba castellanii.

OBJECTIVES: The presence of aforementioned targets and the type of cell death induced by amiodarone in pathogenic eukaryotes like Acanthamoeba castellanii remains to be established. We inferred the presence of homologous targets of amiodarone in A. castellanii compared with humans.

METHODS: This study used bioinformatics exploration for amino acid sequence homology, ligand binding attribute predictions, 3D structural model development, and experimental assays that highlight similarity between certain target proteins in Acanthamoeba as compared to humans.

RESULTS: The sequence identity scores for amino acids and 3D models show that A. castellanii expresses similar types of targets of amiodarone like Na+ v - K+1 v channels, cytochrome P450 3A4, and lanosterol synthase (oxidosqualene cyclase). We show that even though human like L-type and two pore Ca+2 channels are present in A. castellanii, there was no evidence of the expression of T-type voltage dependent Ca+2 channels. Growth assays showed amoebicidal and amoebistatic effects at doses of 40-80μg/ml.

CONCLUSION: The existing bioinformatics tools, ligand binding attribute prediction, and model building offer a specific method to establish homology of proteins, discover drug targets, and facilitate the investigation of the evolution of several types of cardinal ion channels from unicellular eukaryotes to multicellular species as humans.}, } @article {pmid28633034, year = {2017}, author = {Nagy, LG}, title = {Evolution: Complex Multicellular Life with 5,500 Genes.}, journal = {Current biology : CB}, volume = {27}, number = {12}, pages = {R609-R612}, doi = {10.1016/j.cub.2017.04.032}, pmid = {28633034}, issn = {1879-0445}, mesh = {*Ascomycota ; Genomics ; }, abstract = {The origin of complex multicellularity was a major transition in evolution and is generally associated with higher genomic complexity. However, some complex multicellular fungi defy this principle, having small genomes that resemble those of unicellular yeasts rather than those of other complex multicellular organisms.}, } @article {pmid28631149, year = {2017}, author = {Krsmanovic, P}, title = {Vigor of survival determinism: subtle evolutionary gradualism interspersed with robust phylogenetic leaping.}, journal = {Theory in biosciences = Theorie in den Biowissenschaften}, volume = {136}, number = {3-4}, pages = {141-151}, pmid = {28631149}, issn = {1611-7530}, mesh = {Animals ; *Biological Evolution ; Caenorhabditis elegans ; Cell Lineage ; Drosophila melanogaster ; Female ; Genetic Drift ; Genetic Variation ; Genetics, Population ; Genomics ; Male ; Models, Genetic ; Mutagenesis ; Mutation ; *Phylogeny ; Saccharomyces cerevisiae ; *Selection, Genetic ; Stochastic Processes ; }, abstract = {Discussions of the survival determinism concept have previously focused on its primary role in the evolution of early unicellular organisms in the light of findings which have been reported on a number of diseases. The rationale for such parallel was in the view according to which multicellular organisms could be regarded as sophisticated colonies of semi-autonomous, single-celled entities, whereby various diseases were described as conditions arising upon the activation of the respective survival mechanisms in a milieu unsuitable for such robust stress response. The cellular mechanisms that were discussed in these contexts have been known to play various roles in other biological processes. The proposed notion could thereby be further extended to discussion on mechanisms for the implementation of the respective survival pathways in the development of metazoa, considering that they would have been propagated in their evolution for so long. This manuscript first presents a concise overview of the model previously discussed, followed by the discussion on the role of respective mechanism(s) in origins and development of metazoa. Finally, a reflection on the concept in relation to the prominent evolutionary models is put forward to illustrate a broader context of what is being discussed.}, } @article {pmid28630027, year = {2017}, author = {Sapir, L and Tzlil, S}, title = {Talking over the extracellular matrix: How do cells communicate mechanically?.}, journal = {Seminars in cell & developmental biology}, volume = {71}, number = {}, pages = {99-105}, doi = {10.1016/j.semcdb.2017.06.010}, pmid = {28630027}, issn = {1096-3634}, mesh = {Animals ; Biomechanical Phenomena ; Cell Communication ; Cell Movement ; *Extracellular Matrix ; Humans ; Myocardium/cytology ; }, abstract = {Communication between cells enables them to coordinate their activity and is crucial for the differentiation, development, and function of tissues and multicellular organisms. Cell-cell communication is discussed almost exclusively as having a chemical or electrical origin. Only recently, a new mode of cell communication was elucidated: mechanical communication through the extracellular matrix (ECM). Cells can communicate mechanically by responding either to mechanical deformations generated by their neighbors or to a change in the mechanical properties of the ECM induced by a neighboring cell. This newly resolved mode of communication possesses unique features that complement the cellular ability to receive and share information, and to consequently act in a cooperative way with surrounding cells. Herein, we review several examples of mechanical communication, discuss their unique properties, and comment on the major challenges facing the field.}, } @article {pmid28629791, year = {2017}, author = {Xie, N and Ruprich-Robert, G and Chapeland-Leclerc, F and Coppin, E and Lalucque, H and Brun, S and Debuchy, R and Silar, P}, title = {Inositol-phosphate signaling as mediator for growth and sexual reproduction in Podospora anserina.}, journal = {Developmental biology}, volume = {429}, number = {1}, pages = {285-305}, doi = {10.1016/j.ydbio.2017.06.017}, pmid = {28629791}, issn = {1095-564X}, mesh = {Amino Acid Sequence ; Cell Nucleus/metabolism ; Fertility ; Fruiting Bodies, Fungal/metabolism ; Fungal Proteins/chemistry/metabolism ; Genes, Fungal ; Green Fluorescent Proteins/metabolism ; Inositol/metabolism ; Inositol Phosphates/*metabolism ; MAP Kinase Signaling System ; Mosaicism ; Mutation/genetics ; Phenotype ; Pigments, Biological/metabolism ; Podospora/enzymology/genetics/*growth & development/*metabolism ; Protein Transport ; Reproduction ; *Signal Transduction ; Sordariales/metabolism ; Spores, Fungal/metabolism ; Temperature ; Zygote/metabolism ; }, abstract = {The molecular pathways involved in the development of multicellular fruiting bodies in fungi are still not well known. Especially, the interplay between the mycelium, the female tissues and the zygotic tissues of the fruiting bodies is poorly documented. Here, we describe PM154, a new strain of the model ascomycetes Podospora anserina able to mate with itself and that enabled the easy recovery of new mutants affected in fruiting body development. By complete genome sequencing of spod1, one of the new mutants, we identified an inositol phosphate polykinase gene as essential, especially for fruiting body development. A factor present in the wild type and diffusible in mutant hyphae was able to induce the development of the maternal tissues of the fruiting body in spod1, but failed to promote complete development of the zygotic ones. Addition of myo-inositol in the growth medium was able to increase the number of developing fruiting bodies in the wild type, but not in spod1. Overall, the data indicated that inositol and inositol polyphosphates were involved in promoting fruiting body maturation, but also in regulating the number of fruiting bodies that developed after fertilization. The same effect of inositol was seen in two other fungi, Sordaria macrospora and Chaetomium globosum. Key role of the inositol polyphosphate pathway during fruiting body maturation appears thus conserved during the evolution of Sordariales fungi.}, } @article {pmid28627239, year = {2017}, author = {Csaba, G}, title = {Complex multicellular functions at a unicellular eukaryote level: Learning, memory, and immunity.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {64}, number = {2}, pages = {105-120}, doi = {10.1556/030.64.2017.013}, pmid = {28627239}, issn = {1217-8950}, mesh = {Animals ; Eukaryota/genetics/*immunology/*physiology ; Humans ; Learning ; Memory ; }, abstract = {According to experimental data, eukaryote unicellulars are able to learn, have immunity and memory. Learning is carried out in a very primitive form, and the memory is not neural but an epigenetic one. However, this epigenetic memory, which is well justified by the presence and manifestation of hormonal imprinting, is strong and permanent in the life of cell and also in its progenies. This memory is epigenetically executed by the alteration and fixation of methylation pattern of genes without changes in base sequences. The immunity of unicellulars is based on self/non-self discrimination, which leads to the destruction of non-self invaders and utilization of them as nourishment (by phagocytosis). The tools of learning, memory, and immunity of unicellulars are uniformly found in plasma membrane receptors, which formed under the effect of dynamic receptor pattern generation, suggested by Koch et al., and this is the basis of hormonal imprinting, by which the encounter between a chemical substance and the cell is specifically memorized. The receptors and imprinting are also used in the later steps of evolution up to mammals (including man) in each mentioned functions. This means that learning, memory, and immunity can be deduced to a unicellular eukaryote level.}, } @article {pmid28610890, year = {2017}, author = {Brodie, J and Chan, CX and De Clerck, O and Cock, JM and Coelho, SM and Gachon, C and Grossman, AR and Mock, T and Raven, JA and Smith, AG and Yoon, HS and Bhattacharya, D}, title = {The Algal Revolution.}, journal = {Trends in plant science}, volume = {22}, number = {8}, pages = {726-738}, doi = {10.1016/j.tplants.2017.05.005}, pmid = {28610890}, issn = {1878-4372}, support = {BB/L014130/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Biodiversity ; Biological Evolution ; Biotechnology ; Ecology ; Gene Transfer, Horizontal ; *Photosynthesis ; Stramenopiles/*genetics/physiology ; Symbiosis ; }, abstract = {Algae are (mostly) photosynthetic eukaryotes that occupy multiple branches of the tree of life, and are vital for planet function and health. In this review, we highlight a transformative period in studies of the evolution and functioning of this extraordinary group of organisms and their potential for novel applications, wrought by high-throughput 'omic' and reverse genetic methods. We cover the origin and diversification of algal groups, explore advances in understanding the link between phenotype and genotype, consider algal sex determination, and review progress in understanding the roots of algal multicellularity. Experimental evolution studies to determine how algae evolve in changing environments are highlighted, as is their potential as production platforms for compounds of commercial interest, such as biofuel precursors, nutraceuticals, or therapeutics.}, } @article {pmid28605523, year = {2017}, author = {Vergara, Z and Sequeira-Mendes, J and Morata, J and Peiró, R and Hénaff, E and Costas, C and Casacuberta, JM and Gutierrez, C}, title = {Retrotransposons are specified as DNA replication origins in the gene-poor regions of Arabidopsis heterochromatin.}, journal = {Nucleic acids research}, volume = {45}, number = {14}, pages = {8358-8368}, pmid = {28605523}, issn = {1362-4962}, mesh = {Arabidopsis/cytology/*genetics/metabolism ; Cell Line ; Chromatin/genetics/metabolism ; Chromosome Mapping ; *DNA Replication ; DNA, Plant/genetics/metabolism ; GC Rich Sequence/genetics ; Genome, Plant/genetics ; Heterochromatin/*genetics/metabolism ; Histones/metabolism ; Lysine/metabolism ; Methylation ; Microscopy, Confocal ; Replication Origin/*genetics ; Retroelements/*genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription, Genetic ; }, abstract = {Genomic stability depends on faithful genome replication. This is achieved by the concerted activity of thousands of DNA replication origins (ORIs) scattered throughout the genome. The DNA and chromatin features determining ORI specification are not presently known. We have generated a high-resolution genome-wide map of 3230 ORIs in cultured Arabidopsis thaliana cells. Here, we focused on defining the features associated with ORIs in heterochromatin. In pericentromeric gene-poor domains ORIs associate almost exclusively with the retrotransposon class of transposable elements (TEs), in particular of the Gypsy family. ORI activity in retrotransposons occurs independently of TE expression and while maintaining high levels of H3K9me2 and H3K27me1, typical marks of repressed heterochromatin. ORI-TEs largely colocalize with chromatin signatures defining GC-rich heterochromatin. Importantly, TEs with active ORIs contain a local GC content higher than the TEs lacking them. Our results lead us to conclude that ORI colocalization with retrotransposons is determined by their transposition mechanism based on transcription, and a specific chromatin landscape. Our detailed analysis of ORIs responsible for heterochromatin replication has implications on the mechanisms of ORI specification in other multicellular organisms in which retrotransposons are major components of heterochromatin and of the entire genome.}, } @article {pmid28603898, year = {2019}, author = {Dhouailly, D and Godefroit, P and Martin, T and Nonchev, S and Caraguel, F and Oftedal, O}, title = {Getting to the root of scales, feather and hair: As deep as odontodes?.}, journal = {Experimental dermatology}, volume = {28}, number = {4}, pages = {503-508}, doi = {10.1111/exd.13391}, pmid = {28603898}, issn = {1600-0625}, mesh = {Adaptation, Physiological ; Animal Scales/*embryology ; Animals ; *Biological Evolution ; Feathers/*embryology ; *Fossils ; Hair/*embryology ; }, abstract = {While every jawed vertebrate, or its recent ancestor, possesses teeth, skin appendages are characteristic of the living clades: skin denticles (odontodes) in chondrichthyans, dermal scales in teleosts, ducted multicellular glands in amphibians, epidermal scales in squamates, feathers in birds and hair-gland complexes in mammals, all of them showing a dense periodic patterning. While the odontode origin of teleost scales is generally accepted, the origin of both feather and hair is still debated. They appear long before mammals and birds, at least in the Jurassic in mammaliaforms and in ornithodires (pterosaurs and dinosaurs), and are contemporary to scales of early squamates. Epidermal scales might have appeared several times in evolution, and basal amniotes could not have developed a scaled dry integument, as the function of hair follicle requires its association with glands. In areas such as amnion, cornea or plantar pads, the formation of feather and hair is prevented early in embryogenesis, but can be easily reverted by playing with the Wnt/BMP/Shh pathways, which both imply the plasticity and the default competence of ectoderm. Conserved ectodermal/mesenchymal signalling pathways lead to placode formation, while later the crosstalk differs, as well as the final performing tissue(s): both epidermis and dermis for teeth and odontodes, mostly dermis for teleosts scales and only epidermis for squamate scale, feather and hair. We therefore suggest that tooth, dermal scale, epidermal scale, feather and hair evolved in parallel from a shared placode/dermal cell unit, which was present in a common ancestor, an early vertebrate gnathostome with odontodes, ca. 420 million years ago.}, } @article {pmid28592899, year = {2017}, author = {Nan, F and Feng, J and Lv, J and Liu, Q and Fang, K and Gong, C and Xie, S}, title = {Origin and evolutionary history of freshwater Rhodophyta: further insights based on phylogenomic evidence.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {2934}, pmid = {28592899}, issn = {2045-2322}, mesh = {*Biological Evolution ; Evolution, Molecular ; *Fresh Water ; Genes, Plant ; Genetic Variation ; Genome, Chloroplast ; Genome, Mitochondrial ; Genomics/methods ; Phylogeny ; Rhodophyta/*classification/*genetics ; }, abstract = {Freshwater representatives of Rhodophyta were sampled and the complete chloroplast and mitochondrial genomes were determined. Characteristics of the chloroplast and mitochondrial genomes were analyzed and phylogenetic relationship of marine and freshwater Rhodophyta were reconstructed based on the organelle genomes. The freshwater member Compsopogon caeruleus was determined for the largest chloroplast genome among multicellular Rhodophyta up to now. Expansion and subsequent reduction of both the genome size and GC content were observed in the Rhodophyta except for the freshwater Compsopogon caeruleus. It was inferred that the freshwater members of Rhodophyta occurred through diverse origins based on evidence of genome size, GC-content, phylogenomic analysis and divergence time estimation. The freshwater species Compsopogon caeruleus and Hildenbrandia rivularis originated and evolved independently at the inland water, whereas the Bangia atropurpurea, Batrachospermum arcuatum and Thorea hispida are derived from the marine relatives. The typical freshwater representatives Thoreales and Batrachospermales are probably derived from the marine relative Palmaria palmata at approximately 415-484 MYA. The origin and evolutionary history of freshwater Rhodophyta needs to be testified with more organelle genome sequences and wider global sampling.}, } @article {pmid28588313, year = {2017}, author = {Salmeán, AA and Duffieux, D and Harholt, J and Qin, F and Michel, G and Czjzek, M and Willats, WGT and Hervé, C}, title = {Insoluble (1 → 3), (1 → 4)-β-D-glucan is a component of cell walls in brown algae (Phaeophyceae) and is masked by alginates in tissues.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {2880}, pmid = {28588313}, issn = {2045-2322}, mesh = {Alginates/*metabolism ; Cell Wall/*chemistry/*metabolism ; Chromatography, High Pressure Liquid ; Fluorescent Antibody Technique ; Glucans/*chemistry/*metabolism ; Immunohistochemistry ; Organ Specificity ; Phaeophyta/classification/genetics/*metabolism ; Solubility ; }, abstract = {Brown algae are photosynthetic multicellular marine organisms. They belong to the phylum of Stramenopiles, which are not closely related to land plants and green algae. Brown algae share common evolutionary features with other photosynthetic and multicellular organisms, including a carbohydrate-rich cell-wall. Brown algal cell walls are composed predominantly of the polyanionic polysaccharides alginates and fucose-containing sulfated polysaccharides. These polymers are prevalent over neutral and crystalline components, which are believed to be mostly, if not exclusively, cellulose. In an attempt to better understand brown algal cell walls, we performed an extensive glycan array analysis of a wide range of brown algal species. Here we provide the first demonstration that mixed-linkage (1 → 3), (1 → 4)-β-D-glucan (MLG) is common in brown algal cell walls. Ultra-Performance Liquid Chromatography analyses indicate that MLG in brown algae solely consists of trisaccharide units of contiguous (1 → 4)-β-linked glucose residues joined by (1 → 3)-β-linkages. This regular conformation may allow long stretches of the molecule to align and to form well-structured microfibrils. At the tissue level, immunofluorescence studies indicate that MLG epitopes in brown algae are unmasked by a pre-treatment with alginate lyases to remove alginates. These findings are further discussed in terms of the origin and evolution of MLG in the Stramenopile lineage.}, } @article {pmid28584082, year = {2017}, author = {Vergara, HM and Bertucci, PY and Hantz, P and Tosches, MA and Achim, K and Vopalensky, P and Arendt, D}, title = {Whole-organism cellular gene-expression atlas reveals conserved cell types in the ventral nerve cord of Platynereis dumerilii.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {23}, pages = {5878-5885}, pmid = {28584082}, issn = {1091-6490}, mesh = {Algorithms ; Animals ; *Biological Evolution ; Body Patterning/genetics ; Cell Differentiation ; Gene Expression Profiling/methods ; Gene Expression Regulation, Developmental ; Models, Biological ; Neurons/cytology ; Polychaeta/cytology/*genetics ; }, abstract = {The comparative study of cell types is a powerful approach toward deciphering animal evolution. To avoid selection biases, however, comparisons ideally involve all cell types present in a multicellular organism. Here, we use image registration and a newly developed "Profiling by Signal Probability Mapping" algorithm to generate a cellular resolution 3D expression atlas for an entire animal. We investigate three-segmented young worms of the marine annelid Platynereis dumerilii, with a rich diversity of differentiated cells present in relatively low number. Starting from whole-mount expression images for close to 100 neural specification and differentiation genes, our atlas identifies and molecularly characterizes 605 bilateral pairs of neurons at specific locations in the ventral nerve cord. Among these pairs, we identify sets of neurons expressing similar combinations of transcription factors, located at spatially coherent anterior-posterior, dorsal-ventral, and medial-lateral coordinates that we interpret as cell types. Comparison with motor and interneuron types in the vertebrate neural tube indicates conserved combinations, for example, of cell types cospecified by Gata1/2/3 and Tal transcription factors. These include V2b interneurons and the central spinal fluid-contacting Kolmer-Agduhr cells in the vertebrates, and several neuron types in the intermediate ventral ganglionic mass in the annelid. We propose that Kolmer-Agduhr cell-like mechanosensory neurons formed part of the mucociliary sole in protostome-deuterostome ancestors and diversified independently into several neuron types in annelid and vertebrate descendants.}, } @article {pmid28580966, year = {2017}, author = {Driscoll, WW and Travisano, M}, title = {Synergistic cooperation promotes multicellular performance and unicellular free-rider persistence.}, journal = {Nature communications}, volume = {8}, number = {}, pages = {15707}, pmid = {28580966}, issn = {2041-1723}, mesh = {Biological Evolution ; Cluster Analysis ; *Ecology ; Flocculation ; Genotype ; Green Fluorescent Proteins/metabolism ; Kluyveromyces/genetics/*physiology ; Microscopy, Confocal ; Phenotype ; Saccharomyces cerevisiae/genetics/*physiology ; Species Specificity ; Video Recording ; }, abstract = {The evolution of multicellular life requires cooperation among cells, which can be undermined by intra-group selection for selfishness. Theory predicts that selection to avoid non-cooperators limits social interactions among non-relatives, yet previous evolution experiments suggest that intra-group conflict is an outcome, rather than a driver, of incipient multicellular life cycles. Here we report the evolution of multicellularity via two distinct mechanisms of group formation in the unicellular budding yeast Kluyveromyces lactis. Cells remain permanently attached following mitosis, giving rise to clonal clusters (staying together); clusters then reversibly assemble into social groups (coming together). Coming together amplifies the benefits of multicellularity and allows social clusters to collectively outperform solitary clusters. However, cooperation among non-relatives also permits fast-growing unicellular lineages to 'free-ride' during selection for increased size. Cooperation and competition for the benefits of multicellularity promote the stable coexistence of unicellular and multicellular genotypes, underscoring the importance of social and ecological context during the transition to multicellularity.}, } @article {pmid28572690, year = {2017}, author = {Livnat, A}, title = {Simplification, Innateness, and the Absorption of Meaning from Context: How Novelty Arises from Gradual Network Evolution.}, journal = {Evolutionary biology}, volume = {44}, number = {2}, pages = {145-189}, pmid = {28572690}, issn = {0071-3260}, abstract = {How does new genetic information arise? Traditional thinking holds that mutation happens by accident and then spreads in the population by either natural selection or random genetic drift. There have been at least two fundamental conceptual problems with imagining an alternative. First, it seemed that the only alternative is a mutation that responds "smartly" to the immediate environment; but in complex multicellulars, it is hard to imagine how this could be implemented. Second, if there were mechanisms of mutation that "knew" what genetic changes would be favored in a given environment, this would have only begged the question of how they acquired that particular knowledge to begin with. This paper offers an alternative that avoids these problems. It holds that mutational mechanisms act on information that is in the genome, based on considerations of simplicity, parsimony, elegance, etc. (which are different than fitness considerations). This simplification process, under the performance pressure exerted by selection, not only leads to the improvement of adaptations but also creates elements that have the capacity to serve in new contexts they were not originally selected for. Novelty, then, arises at the system level from emergent interactions between such elements. Thus, mechanistically driven mutation neither requires Lamarckian transmission nor closes the door on novelty, because the changes it implements interact with one another globally in surprising and beneficial ways. Finally, I argue, for example, that genes used together are fused together; that simplification leads to complexity; and that evolution and learning are conceptually linked.}, } @article {pmid28571799, year = {2017}, author = {Salerian, AJ}, title = {Human body may produce bacteria.}, journal = {Medical hypotheses}, volume = {103}, number = {}, pages = {131-132}, doi = {10.1016/j.mehy.2017.05.005}, pmid = {28571799}, issn = {1532-2777}, mesh = {Animals ; *Bacteria ; *Bacterial Physiological Phenomena ; Fermentation ; *Human Body ; Humans ; Models, Theoretical ; Muscles/physiology ; Origin of Life ; }, abstract = {"Human body may produce bacteria" proposes that human body may produce bacteria and represent an independent source of infections contrary to the current paradigm of infectious disorders proposed by Louis Pasteur in 1880. The following observations are consistent with this hypothesis: A. Bidirectional transformations of both living and nonliving things have been commonly observed in nature. B. Complex multicellular organisms harbor the necessary properties to produce bacteria (water, nitrogen and oxygen). C. Physical laws suggest any previously observed phenomenon or action will occur again (life began on earth; a non living thing). D. Animal muscle cells may generate energy (fermentation). E. Sterilized food products (i.e. boiled eggs), may produce bacteria and fungus under special conditions and without any exposure to foreign living cells. "Human body may produce bacteria" may challenge the current medical paradigm that views human infectious disorders as the exclusive causative byproducts of invading foreign cells. It may also introduce new avenues to treat infectious disorders.}, } @article {pmid28560344, year = {2017}, author = {Knoll, AH and Nowak, MA}, title = {The timetable of evolution.}, journal = {Science advances}, volume = {3}, number = {5}, pages = {e1603076}, pmid = {28560344}, issn = {2375-2548}, mesh = {*Biological Evolution ; *Ecosystem ; *Models, Biological ; }, abstract = {The integration of fossils, phylogeny, and geochronology has resulted in an increasingly well-resolved timetable of evolution. Life appears to have taken root before the earliest known minimally metamorphosed sedimentary rocks were deposited, but for a billion years or more, evolution played out beneath an essentially anoxic atmosphere. Oxygen concentrations in the atmosphere and surface oceans first rose in the Great Oxygenation Event (GOE) 2.4 billion years ago, and a second increase beginning in the later Neoproterozoic Era [Neoproterozoic Oxygenation Event (NOE)] established the redox profile of modern oceans. The GOE facilitated the emergence of eukaryotes, whereas the NOE is associated with large and complex multicellular organisms. Thus, the GOE and NOE are fundamental pacemakers for evolution. On the time scale of Earth's entire 4 billion-year history, the evolutionary dynamics of the planet's biosphere appears to be fast, and the pace of evolution is largely determined by physical changes of the planet. However, in Phanerozoic ecosystems, interactions between new functions enabled by the accumulation of characters in a complex regulatory environment and changing biological components of effective environments appear to have an important influence on the timing of evolutionary innovations. On the much shorter time scale of transient environmental perturbations, such as those associated with mass extinctions, rates of genetic accommodation may have been limiting for life.}, } @article {pmid28551499, year = {2017}, author = {Shakiba, N and Zandstra, PW}, title = {Engineering cell fitness: lessons for regenerative medicine.}, journal = {Current opinion in biotechnology}, volume = {47}, number = {}, pages = {7-15}, doi = {10.1016/j.copbio.2017.05.005}, pmid = {28551499}, issn = {1879-0429}, support = {MOP 57885//CIHR/Canada ; }, mesh = {Animals ; Cell Engineering/*methods ; Humans ; Models, Biological ; Regenerative Medicine/*methods ; Tissue Engineering ; }, abstract = {Cell competition results in the loss of weaker cells and the dominance of stronger cells. So-called 'loser' cells are either removed by active elimination or by limiting their access to survival factors. Recently, competition has been shown to serve as a surveillance mechanism against emerging aberrant cells in both the developing and adult organism, contributing to overall organism fitness and survival. Here, we explore the origins and implications of cell competition in development, tissue homeostasis, and in vitro culture. We also provide a forward look on the use of cell competition to interpret multicellular dynamics while offering a perspective on harnessing competition to engineer cells with optimized and controllable fitness characteristics for regenerative medicine applications.}, } @article {pmid28550046, year = {2017}, author = {Vijg, J and Dong, X and Milholland, B and Zhang, L}, title = {Genome instability: a conserved mechanism of ageing?.}, journal = {Essays in biochemistry}, volume = {61}, number = {3}, pages = {305-315}, pmid = {28550046}, issn = {1744-1358}, support = {P01 AG017242/AG/NIA NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; P30 AG038072/AG/NIA NIH HHS/United States ; R01 CA180126/CA/NCI NIH HHS/United States ; }, mesh = {Aging/genetics/*physiology ; Animals ; DNA Repair/genetics/physiology ; Genomic Instability/genetics/*physiology ; Humans ; Mutation/genetics ; }, abstract = {DNA is the carrier of genetic information and the primary template from which all cellular information is ultimately derived. Changes in the DNA information content through mutation generate diversity for evolution through natural selection but are also a source of deleterious effects. It has since long been hypothesized that mutation accumulation in somatic cells of multicellular organisms could causally contribute to age-related cellular degeneration and death. Assays to detect different types of mutations, from base substitutions to large chromosomal aberrations, have been developed and show unequivocally that mutations accumulate in different tissues and cell types of ageing humans and animals. More recently, next-generation sequencing-based methods have been developed to accurately determine the complete landscape of base substitution mutations in single cells. The first results show that the somatic mutation rate is much higher than the germline mutation rate and that base substitution loads in somatic cells are high enough to potentially affect cellular function.}, } @article {pmid28529980, year = {2017}, author = {Moran, Y and Agron, M and Praher, D and Technau, U}, title = {The evolutionary origin of plant and animal microRNAs.}, journal = {Nature ecology & evolution}, volume = {1}, number = {3}, pages = {27}, pmid = {28529980}, issn = {2397-334X}, support = {637456/ERC_/European Research Council/International ; }, abstract = {microRNAs (miRNAs) are a unique class of short endogenous RNAs that became known in the last few decades as major players in gene regulation at the post-transcriptional level. Their regulatory roles make miRNAs crucial for normal development and physiology in several distinct groups of eukaryotes including plants and animals. The common notion in the field is that miRNAs have evolved independently in those distinct lineages, but recent evidence from non-bilaterian metazoans, plants, as well as various algae raise the possibility that already the last common ancestor of these lineages might have employed a miRNA pathway for post-transcriptional regulation. In this review we present the commonalities and differences of the miRNA pathways in various eukaryotes and discuss the contrasting scenarios of their possible evolutionary origin and their proposed link to organismal complexity and multicellularity.}, } @article {pmid28525299, year = {2017}, author = {Berbee, ML and James, TY and Strullu-Derrien, C}, title = {Early Diverging Fungi: Diversity and Impact at the Dawn of Terrestrial Life.}, journal = {Annual review of microbiology}, volume = {71}, number = {}, pages = {41-60}, doi = {10.1146/annurev-micro-030117-020324}, pmid = {28525299}, issn = {1545-3251}, mesh = {*Evolution, Molecular ; Fungi/*classification/*genetics ; *Genetic Variation ; }, abstract = {As decomposers or plant pathogens, fungi deploy invasive growth and powerful carbohydrate active enzymes to reduce multicellular plant tissues to humus and simple sugars. Fungi are perhaps also the most important mutualistic symbionts in modern ecosystems, transporting poorly soluble mineral nutrients to plants and thus enhancing the growth of vegetation. However, at their origin over a billion years ago, fungi, like plants and animals, were unicellular marine microbes. Like the other multicellular kingdoms, Fungi evolved increased size, complexity, and metabolic functioning. Interactions of fungi with plants changed terrestrial ecology and geology and modified the Earth's atmosphere. In this review, we discuss the diversification and ecological roles of the fungi over their first 600 million years, from their origin through their colonization of land, drawing on phylogenomic evidence for their relationships and metabolic capabilities and on molecular dating, fossils, and modeling of Earth's paleoclimate.}, } @article {pmid28509401, year = {2017}, author = {Dittami, SM and Heesch, S and Olsen, JL and Collén, J}, title = {Transitions between marine and freshwater environments provide new clues about the origins of multicellular plants and algae.}, journal = {Journal of phycology}, volume = {53}, number = {4}, pages = {731-745}, doi = {10.1111/jpy.12547}, pmid = {28509401}, issn = {1529-8817}, mesh = {Adaptation, Biological ; *Biological Evolution ; *Ecosystem ; Fresh Water ; *Phaeophyta ; *Plants ; Seawater ; }, abstract = {Marine-freshwater and freshwater-marine transitions have been key events in the evolution of life, and most major groups of organisms have independently undergone such events at least once in their history. Here, we first compile an inventory of bidirectional freshwater and marine transitions in multicellular photosynthetic eukaryotes. While green and red algae have mastered multiple transitions in both directions, brown algae have colonized freshwater on a maximum of six known occasions, and angiosperms have made the transition to marine environments only two or three times. Next, we review the early evolutionary events leading to the colonization of current habitats. It is commonly assumed that the conquest of land proceeded in a sequence from marine to freshwater habitats. However, recent evidence suggests that early photosynthetic eukaryotes may have arisen in subaerial or freshwater environments and only later colonized marine environments as hypersaline oceans were diluted to the contemporary level. Although this hypothesis remains speculative, it is important to keep these alternative scenarios in mind when interpreting the current habitat distribution of plants and algae. Finally, we discuss the roles of structural and functional adaptations of the cell wall, reactive oxygen species scavengers, osmoregulation, and reproduction. These are central for acclimatization to freshwater or to marine environments. We observe that successful transitions appear to have occurred more frequently in morphologically simple forms and conclude that, in addition to physiological studies of euryhaline species, comparative studies of closely related species fully adapted to one or the other environment are necessary to better understand the adaptive processes.}, } @article {pmid28508537, year = {2018}, author = {Boomsma, JJ and Gawne, R}, title = {Superorganismality and caste differentiation as points of no return: how the major evolutionary transitions were lost in translation.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {28-54}, doi = {10.1111/brv.12330}, pmid = {28508537}, issn = {1469-185X}, mesh = {Animals ; *Behavior, Animal ; *Biological Evolution ; Insecta/*genetics/*physiology ; Selection, Genetic ; *Social Behavior ; }, abstract = {More than a century ago, William Morton Wheeler proposed that social insect colonies can be regarded as superorganisms when they have morphologically differentiated reproductive and nursing castes that are analogous to the metazoan germ-line and soma. Following the rise of sociobiology in the 1970s, Wheeler's insights were largely neglected, and we were left with multiple new superorganism concepts that are mutually inconsistent and uninformative on how superorganismality originated. These difficulties can be traced to the broadened sociobiological concept of eusociality, which denies that physical queen-worker caste differentiation is a universal hallmark of superorganismal colonies. Unlike early evolutionary naturalists and geneticists such as Weismann, Huxley, Fisher and Haldane, who set out to explain the acquisition of an unmated worker caste, the goal of sociobiology was to understand the evolution of eusociality, a broad-brush convenience category that covers most forms of cooperative breeding. By lumping a diverse spectrum of social systems into a single category, and drawing attention away from the evolution of distinct quantifiable traits, the sociobiological tradition has impeded straightforward connections between inclusive fitness theory and the major evolutionary transitions paradigm for understanding irreversible shifts to higher organizational complexity. We evaluate the history by which these inconsistencies accumulated, develop a common-cause approach for understanding the origins of all major transitions in eukaryote hierarchical complexity, and use Hamilton's rule to argue that they are directly comparable. We show that only Wheeler's original definition of superorganismality can be unambiguously linked to irreversible evolutionary transitions from context-dependent reproductive altruism to unconditional differentiation of permanently unmated castes in the ants, corbiculate bees, vespine wasps and higher termites. We argue that strictly monogamous parents were a necessary, albeit not sufficient condition for all transitions to superorganismality, analogous to single-zygote bottlenecking being a necessary but not sufficient condition for the convergent origins of complex soma across multicellular eukaryotes. We infer that conflict reduction was not a necessary condition for the origin of any of these major transitions, and conclude that controversies over the status of inclusive fitness theory primarily emanate from the arbitrarily defined sociobiological concepts of superorganismality and eusociality, not from the theory itself.}, } @article {pmid28506208, year = {2017}, author = {Labocha, MK and Yuan, W and Aleman-Meza, B and Zhong, W}, title = {A strategy to apply quantitative epistasis analysis on developmental traits.}, journal = {BMC genetics}, volume = {18}, number = {1}, pages = {42}, pmid = {28506208}, issn = {1471-2156}, support = {K99 HG004724/HG/NHGRI NIH HHS/United States ; R00 HG004724/HG/NHGRI NIH HHS/United States ; R01 DA018341/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*genetics/*growth & development ; Caenorhabditis elegans Proteins/genetics ; *Epistasis, Genetic ; High-Throughput Nucleotide Sequencing/methods ; Models, Genetic ; *Quantitative Trait Loci ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Genetic interactions are keys to understand complex traits and evolution. Epistasis analysis is an effective method to map genetic interactions. Large-scale quantitative epistasis analysis has been well established for single cells. However, there is a substantial lack of such studies in multicellular organisms and their complex phenotypes such as development. Here we present a method to extend quantitative epistasis analysis to developmental traits.

METHODS: In the nematode Caenorhabditis elegans, we applied RNA interference on mutants to inactivate two genes, used an imaging system to quantitatively measure phenotypes, and developed a set of statistical methods to extract genetic interactions from phenotypic measurement.

RESULTS: Using two different C. elegans developmental phenotypes, body length and sex ratio, as examples, we showed that this method could accommodate various metazoan phenotypes with performances comparable to those methods in single cell growth studies. Comparing with qualitative observations, this method of quantitative epistasis enabled detection of new interactions involving subtle phenotypes. For example, several sex-ratio genes were found to interact with brc-1 and brd-1, the orthologs of the human breast cancer genes BRCA1 and BARD1, respectively. We confirmed the brc-1 interactions with the following genes in DNA damage response: C34F6.1, him-3 (ortholog of HORMAD1, HORMAD2), sdc-1, and set-2 (ortholog of SETD1A, SETD1B, KMT2C, KMT2D), validating the effectiveness of our method in detecting genetic interactions.

CONCLUSIONS: We developed a reliable, high-throughput method for quantitative epistasis analysis of developmental phenotypes.}, } @article {pmid28505429, year = {2017}, author = {Siu, KH and Chen, W}, title = {Control of the Yeast Mating Pathway by Reconstitution of Functional α-Factor Using Split Intein-Catalyzed Reactions.}, journal = {ACS synthetic biology}, volume = {6}, number = {8}, pages = {1453-1460}, doi = {10.1021/acssynbio.7b00078}, pmid = {28505429}, issn = {2161-5063}, mesh = {Catalysis ; Gene Expression Regulation, Fungal/*genetics ; Genes, Mating Type, Fungal/*genetics ; Inteins/*genetics ; Metabolic Engineering/*methods ; Metabolic Networks and Pathways/*genetics ; Models, Genetic ; Pheromones/*genetics ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/genetics ; Signal Transduction/genetics ; }, abstract = {Synthetic control strategies using signaling peptides to regulate and coordinate cellular behaviors in multicellular organisms and synthetic consortia remain largely underdeveloped because of the complexities necessitated by heterologous peptide expression. Using recombinant proteins that exploit split intein-mediated reactions, we presented here a new strategy for reconstituting functional signaling peptides capable of eliciting desired cellular responses in S. cerevisiae. These designs can potentially be tailored to any signaling peptides to be reconstituted, as the split inteins are promiscuous and both the peptides and the reactions are amenable to changes by directed evolution and other protein engineering tools, thereby offering a general strategy to implement synthetic control strategies in a large variety of applications.}, } @article {pmid28498101, year = {2017}, author = {Hinman, V and Cary, G}, title = {The evolution of gene regulation.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {28498101}, issn = {2050-084X}, mesh = {Animals ; *Gene Expression Regulation ; *Histone Code ; Protein Processing, Post-Translational ; }, abstract = {The gene regulation mechanisms necessary for the development of complex multicellular animals have been found in sponges.}, } @article {pmid28497122, year = {2017}, author = {Franco-Obregón, A and Gilbert, JA}, title = {The Microbiome-Mitochondrion Connection: Common Ancestries, Common Mechanisms, Common Goals.}, journal = {mSystems}, volume = {2}, number = {3}, pages = {}, pmid = {28497122}, issn = {2379-5077}, abstract = {Lynn Margulis in the 1960s elegantly proposed a shared phylogenetic history between bacteria and mitochondria; this relationship has since become a cornerstone of modern cellular biology. Yet, an interesting facet of the interaction between the microbiome and mitochondria has been mostly ignored, that of the systems biology relationship that underpins host health and longevity. The mitochondria are descendants of primordial aerobic pleomorphic bacteria (likely genus Rickettsia) that entered (literally and functionally) into a mutualistic partnership with ancient anaerobic microbes (likely Archaea). A stable symbiosis was established, given the metabolic versatility of the early mitochondria, which were capable of providing energy with or without oxygen, whereas nutrient gathering was the assumed responsibility of the host. While microbial relationships with single-cell protists must have occurred in the past, as they occur today, the evolution of multicellular organisms generated a new framework for symbiosis with the microbial world, taking the ancient partnership to an entirely new level. Cell-cell communication between microbes and single-cell protists was augmented through multicellularity to allow distant communication between the host cells and the microbiome, resulting in the development of complex metabolic relationships and an immune system to manage these interactions. Thus, the host is now the body and its resident mitochondria, and the microbiome is an essential supplier of metabolites that act at the level of mitochondria in skeletal muscle to stabilize host metabolism. We humans are caretakers of a profoundly vast and diverse microbiota, the majority of which resides in the gut. Indeed, the microbial genetic diversity of our microbiota outstrips our own by several orders of magnitude, and the cellular abundance is roughly equivalent to our somatic selves. Modern clinical science has elegantly highlighted the importance of the microbiome for metabolic health and well-being. This perspective underscores one fundamental facet of this symbiosis, the ancestral mitochondrion-microbiome axis.}, } @article {pmid28485371, year = {2017}, author = {Milholland, B and Dong, X and Zhang, L and Hao, X and Suh, Y and Vijg, J}, title = {Differences between germline and somatic mutation rates in humans and mice.}, journal = {Nature communications}, volume = {8}, number = {}, pages = {15183}, pmid = {28485371}, issn = {2041-1723}, support = {P01 AG017242/AG/NIA NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Child ; Genome ; Germ-Line Mutation/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mice, Inbred C57BL ; *Mutation Rate ; }, abstract = {The germline mutation rate has been extensively studied and has been found to vary greatly between species, but much less is known about the somatic mutation rate in multicellular organisms, which remains very difficult to determine. Here, we present data on somatic mutation rates in mice and humans, obtained by sequencing single cells and clones derived from primary fibroblasts, which allows us to make the first direct comparison with germline mutation rates in these two species. The results indicate that the somatic mutation rate is almost two orders of magnitude higher than the germline mutation rate and that both mutation rates are significantly higher in mice than in humans. Our findings demonstrate both the privileged status of germline genome integrity and species-specific differences in genome maintenance.}, } @article {pmid28484005, year = {2017}, author = {Trigos, AS and Pearson, RB and Papenfuss, AT and Goode, DL}, title = {Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {24}, pages = {6406-6411}, pmid = {28484005}, issn = {1091-6490}, mesh = {Animals ; Carcinogenesis/genetics ; Cell Transformation, Neoplastic/genetics ; *Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genome, Human ; Humans ; Models, Genetic ; Neoplasms/etiology/*genetics ; Oncogenes ; Phenotype ; Stress, Physiological/genetics ; Systems Biology ; }, abstract = {Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer.}, } @article {pmid28481398, year = {2017}, author = {Lei, Y and Anders, HJ}, title = {Evolutionary trade-offs in kidney injury and repair.}, journal = {Histology and histopathology}, volume = {32}, number = {11}, pages = {1099-1113}, doi = {10.14670/HH-11-900}, pmid = {28481398}, issn = {1699-5848}, mesh = {Animals ; *Biological Evolution ; Humans ; Kidney/*injuries ; *Regeneration ; }, abstract = {Evolutionary medicine has proven helpful to understand the origin of human disease, e.g. in identifying causal roles of recent environmental changes impacting on human physiology (environment-phenotype mismatch). In contrast, diseases affecting only a limited number of members of a species often originate from evolutionary trade-offs for usually physiologic adaptations assuring reproductive success in the context of extrinsic threats. For example, the G1 and G2 variants of the APOL1 gene supporting control of Trypanosoma infection come with the trade-off that they promote the progression of kidney disease. In this review we extend the concept of evolutionary nephrology by discussing how the physiologic adaptations (danger responses) to tissue injury create evolutionary trade-offs that drive histopathological changes underlying acute and chronic kidney diseases. The evolution of multicellular organisms positively selected a number of danger response programs for their overwhelming benefits in assuring survival such as clotting, inflammation, epithelial healing and mesenchymal healing, i.e. fibrosis and sclerosis. Upon kidney injury these danger programs often present as pathomechanisms driving persistent nephron loss and renal failure. We explore how classic kidney disease entities involve insufficient or overshooting activation of these danger response programs for which the underlying genetic basis remains largely to be defined. Dissecting the causative and hierarchical relationships between danger programs should help to identify molecular targets to control kidney injury and to improve disease outcomes.}, } @article {pmid28479986, year = {2017}, author = {van Duijn, M}, title = {Phylogenetic origins of biological cognition: convergent patterns in the early evolution of learning.}, journal = {Interface focus}, volume = {7}, number = {3}, pages = {20160158}, pmid = {28479986}, issn = {2042-8898}, abstract = {Various forms of elementary learning have recently been discovered in organisms lacking a nervous system, such as protists, fungi and plants. This finding has fundamental implications for how we view the role of convergent evolution in biological cognition. In this article, I first review the evidence for basic forms of learning in aneural organisms, focusing particularly on habituation and classical conditioning and considering the plausibility for convergent evolution of these capacities. Next, I examine the possible role of convergent evolution regarding these basic learning abilities during the early evolution of nervous systems. The evolution of nervous systems set the stage for at least two major events relevant to convergent evolution that are central to biological cognition: (i) nervous systems evolved, perhaps more than once, because of strong selection pressures for sustaining sensorimotor strategies in increasingly larger multicellular organisms and (ii) associative learning was a subsequent adaptation that evolved multiple times within the neuralia. Although convergent evolution of basic forms of learning among distantly related organisms such as protists, plants and neuralia is highly plausible, more research is needed to verify whether these forms of learning within the neuralia arose through convergent or parallel evolution.}, } @article {pmid28479598, year = {2017}, author = {Sebé-Pedrós, A and Degnan, BM and Ruiz-Trillo, I}, title = {The origin of Metazoa: a unicellular perspective.}, journal = {Nature reviews. Genetics}, volume = {18}, number = {8}, pages = {498-512}, pmid = {28479598}, issn = {1471-0064}, mesh = {Animals ; *Biological Evolution ; Eukaryota/classification/cytology/*genetics ; Humans ; Phylogeny ; }, abstract = {The first animals evolved from an unknown single-celled ancestor in the Precambrian period. Recently, the identification and characterization of the genomic and cellular traits of the protists most closely related to animals have shed light on the origin of animals. Comparisons of animals with these unicellular relatives allow us to reconstruct the first evolutionary steps towards animal multicellularity. Here, we review the results of these investigations and discuss their implications for understanding the earliest stages of animal evolution, including the origin of metazoan genes and genome function.}, } @article {pmid28459980, year = {2017}, author = {Fares, MA and Sabater-Muñoz, B and Toft, C}, title = {Genome Mutational and Transcriptional Hotspots Are Traps for Duplicated Genes and Sources of Adaptations.}, journal = {Genome biology and evolution}, volume = {9}, number = {5}, pages = {1229-1240}, pmid = {28459980}, issn = {1759-6653}, mesh = {Adaptation, Biological ; *Gene Duplication ; *Mutation ; Mutation Rate ; Promoter Regions, Genetic ; Saccharomyces cerevisiae/*genetics/*physiology ; Stress, Physiological ; *Transcription, Genetic ; }, abstract = {Gene duplication generates new genetic material, which has been shown to lead to major innovations in unicellular and multicellular organisms. A whole-genome duplication occurred in the ancestor of Saccharomyces yeast species but 92% of duplicates returned to single-copy genes shortly after duplication. The persisting duplicated genes in Saccharomyces led to the origin of major metabolic innovations, which have been the source of the unique biotechnological capabilities in the Baker's yeast Saccharomyces cerevisiae. What factors have determined the fate of duplicated genes remains unknown. Here, we report the first demonstration that the local genome mutation and transcription rates determine the fate of duplicates. We show, for the first time, a preferential location of duplicated genes in the mutational and transcriptional hotspots of S. cerevisiae genome. The mechanism of duplication matters, with whole-genome duplicates exhibiting different preservation trends compared to small-scale duplicates. Genome mutational and transcriptional hotspots are rich in duplicates with large repetitive promoter elements. Saccharomyces cerevisiae shows more tolerance to deleterious mutations in duplicates with repetitive promoter elements, which in turn exhibit higher transcriptional plasticity against environmental perturbations. Our data demonstrate that the genome traps duplicates through the accelerated regulatory and functional divergence of their gene copies providing a source of novel adaptations in yeast.}, } @article {pmid28457024, year = {2017}, author = {Golstein, P}, title = {Conserved nucleolar stress at the onset of cell death.}, journal = {The FEBS journal}, volume = {284}, number = {22}, pages = {3791-3800}, doi = {10.1111/febs.14095}, pmid = {28457024}, issn = {1742-4658}, mesh = {Animals ; *Cell Death ; Cell Nucleolus/metabolism/*pathology ; Humans ; Nuclear Proteins/*metabolism ; *Stress, Physiological ; }, abstract = {Cell death pervasiveness among multicellular eukaryotes suggested that some core steps of cell death may be conserved. This could be addressed by comparing the course of cell death in organisms belonging to distinct eukaryotic kingdoms. A search for early cell death events in a protist revealed nucleolar disorganization similar to the nucleolar stress often reported in dying animal cells. This indicated a conserved role for the nucleolus at the onset of eukaryotic cell death and leads one to consider the course of cell death as a succession of unequally conserved modules.}, } @article {pmid28453786, year = {2017}, author = {Porath, HT and Schaffer, AA and Kaniewska, P and Alon, S and Eisenberg, E and Rosenthal, J and Levanon, EY and Levy, O}, title = {A-to-I RNA Editing in the Earliest-Diverging Eumetazoan Phyla.}, journal = {Molecular biology and evolution}, volume = {34}, number = {8}, pages = {1890-1901}, pmid = {28453786}, issn = {1537-1719}, support = {311257/ERC_/European Research Council/International ; }, mesh = {Adenosine Deaminase/*genetics/metabolism ; Animals ; Anthozoa/*genetics/metabolism ; Base Sequence ; Evolution, Molecular ; Genome ; Genomics ; Humans ; Mammals/genetics ; Phylogeny ; RNA ; RNA Editing/*genetics ; RNA, Messenger/genetics ; RNA-Binding Proteins/genetics ; }, abstract = {The highly conserved ADAR enzymes, found in all multicellular metazoans, catalyze the editing of mRNA transcripts by the deamination of adenosines to inosines. This type of editing has two general outcomes: site specific editing, which frequently leads to recoding, and clustered editing, which is usually found in transcribed genomic repeats. Here, for the first time, we looked for both editing of isolated sites and clustered, non-specific sites in a basal metazoan, the coral Acropora millepora during spawning event, in order to reveal its editing pattern. We found that the coral editome resembles the mammalian one: it contains more than 500,000 sites, virtually all of which are clustered in non-coding regions that are enriched for predicted dsRNA structures. RNA editing levels were increased during spawning and increased further still in newly released gametes. This may suggest that editing plays a role in introducing variability in coral gametes.}, } @article {pmid28450045, year = {2017}, author = {Wang, X and Junior, JCB and Mishra, B and Lushnikova, T and Epand, RM and Wang, G}, title = {Arginine-lysine positional swap of the LL-37 peptides reveals evolutional advantages of the native sequence and leads to bacterial probes.}, journal = {Biochimica et biophysica acta. Biomembranes}, volume = {1859}, number = {8}, pages = {1350-1361}, pmid = {28450045}, issn = {0005-2736}, support = {R01 AI105147/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Anti-Bacterial Agents/*pharmacology ; Antimicrobial Cationic Peptides/*pharmacology ; Arginine/*chemistry ; Cardiolipins/chemistry/isolation & purification ; Cell Membrane/chemistry/*drug effects ; Cell Membrane Permeability/drug effects ; Escherichia coli/chemistry/drug effects/growth & development ; Humans ; Hydrogen-Ion Concentration ; Klebsiella pneumoniae/chemistry/drug effects/growth & development ; Lysine/*chemistry ; Microbial Sensitivity Tests ; Models, Molecular ; Peptides/pharmacology ; Phosphatidylethanolamines/chemistry/isolation & purification ; Phosphatidylglycerols/chemistry/isolation & purification ; Pseudomonas aeruginosa/chemistry/drug effects/growth & development ; Species Specificity ; Staphylococcus aureus/chemistry/drug effects/growth & development ; Structure-Activity Relationship ; Cathelicidins ; }, abstract = {Antimicrobial peptides are essential components of the innate immune system of multicellular organisms. Although cationic and hydrophobic amino acids are known determinants of these amphipathic molecules for bacterial killing, it is not clear how lysine-arginine (K-R) positional swaps influence peptide structure and activity. This study addresses this question by investigating two groups of peptides (GF-17 and 17BIPHE2) derived from human cathelicidin LL-37. K-R positional swap showed little effect on minimal inhibitory concentrations of the peptides. However, there are clear differences in bacterial killing kinetics. The membrane permeation patterns vary with peptide and bacterial types, but not changes in fluorescent dyes, salts or pH. In general, the original peptide is more efficient in bacterial killing, but less toxic to human cells, than the K-R swapped peptides, revealing the evolutionary significance of the native sequence for host defense. The characteristic membrane permeation patterns for different bacteria suggest a possible application of these K-R positional-swapped peptides as molecular probes for the type of bacteria. Such differences are related to bacterial membrane compositions: minimal for Gram-positive Staphylococcus aureus with essentially all anionic lipids (cardiolipin and phosphatidylglycerol), but evident for Gram-negative Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli with a mixture of phosphatidylethanolamine and phosphatidylglycerol. Biophysical characterization found similar structures and binding affinities for these peptides in vesicle systems mimicking E. coli and S. aureus. It seems that interfacial arginines of GF-17 are preferred over lysines in bacterial membrane permeation. Our study sheds new light on the design of cationic amphipathic peptides.}, } @article {pmid28441401, year = {2017}, author = {Cisneros, L and Bussey, KJ and Orr, AJ and Miočević, M and Lineweaver, CH and Davies, P}, title = {Ancient genes establish stress-induced mutation as a hallmark of cancer.}, journal = {PloS one}, volume = {12}, number = {4}, pages = {e0176258}, pmid = {28441401}, issn = {1932-6203}, mesh = {Animals ; Cell Cycle/genetics ; DNA Repair/genetics ; Databases, Genetic ; Humans ; *Mutation ; Neoplasms/*genetics ; *Oncogenes ; Phenotype ; Phylogeny ; }, abstract = {Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cancer and whose mutations are functionally important for the emergence of the cancer phenotype evolved within the past 1000 million years, and thus would exhibit an age distribution that is skewed to younger genes. In order to investigate these hypotheses we estimated the evolutionary ages of all human genes and then studied the probability of mutation and their biological function in relation to their age and genomic location for both normal germline and cancer contexts. We observed that under a model of uniform random mutation across the genome, controlled for gene size, genes less than 500 MY were more frequently mutated in both cases. Paradoxically, causal genes, defined in the COSMIC Cancer Gene Census, were depleted in this age group. When we used functional enrichment analysis to explain this unexpected result we discovered that COSMIC genes with recessive disease phenotypes were enriched for DNA repair and cell cycle control. The non-mutated genes in these pathways are orthologous to those underlying stress-induced mutation in bacteria, which results in the clustering of single nucleotide variations. COSMIC genes were less common in regions where the probability of observing mutational clusters is high, although they are approximately 2-fold more likely to harbor mutational clusters compared to other human genes. Our results suggest this ancient mutational response to stress that evolved among prokaryotes was co-opted to maintain diversity in the germline and immune system, while the original phenotype is restored in cancer. Reversion to a stress-induced mutational response is a hallmark of cancer that allows for effectively searching "protected" genome space where genes causally implicated in cancer are located and underlies the high adaptive potential and concomitant therapeutic resistance that is characteristic of cancer.}, } @article {pmid28427949, year = {2017}, author = {Freese, JM and Lane, CE}, title = {Parasitism finds many solutions to the same problems in red algae (Florideophyceae, Rhodophyta).}, journal = {Molecular and biochemical parasitology}, volume = {214}, number = {}, pages = {105-111}, doi = {10.1016/j.molbiopara.2017.04.006}, pmid = {28427949}, issn = {1872-9428}, mesh = {*Biological Evolution ; *Host-Parasite Interactions ; Microscopy ; Phylogeny ; Rhodophyta/classification/cytology/*genetics/*physiology ; }, abstract = {Parasitic red algae evolve from a common ancestor with their hosts, parasitizing cousins using familiar cellular mechanisms. They have independently evolved over one hundred times within the exclusively multicellular red algal class Florideophyceae. Reduced morphology, a lack of pigmentation, and direct cell-cell connections with their hosts are markers of red algal parasitism. With so many potential evolutionary pathways, red algal parasite diversity offers a unique test case to understand the earliest stages of this lifestyle transition. Molecular and morphological investigations led to the categorization of these parasites based on their relationship to their host. "Adelphoparasites" are phylogenetically close to their hosts, often infecting a sister species, whereas "alloparasites" are more distantly related to their hosts. The differentiation of these parasites, based on their phylogenetic relationship to their host, has resulted in a simplified classification of these parasites that may not reflect the many evolutionary pathways they take to arrive at a similar endpoint. Accordingly, many parasites fall into a gray area between adelphoparasite and alloparasite definitions, challenging the established features we use to classify them. Molecular phylogenetic research has been essential in identifying gaps in knowledge, but microscopy needs to be reincorporated in order to address red algal parasite developmental variation to establish a new paradigm. The joint utilization of molecular and microscopic methods will be critical in identifying the genomic and physiological traits of both nascent and well-established parasites.}, } @article {pmid28427910, year = {2017}, author = {Bury-Moné, S and Sclavi, B}, title = {Stochasticity of gene expression as a motor of epigenetics in bacteria: from individual to collective behaviors.}, journal = {Research in microbiology}, volume = {168}, number = {6}, pages = {503-514}, doi = {10.1016/j.resmic.2017.03.009}, pmid = {28427910}, issn = {1769-7123}, mesh = {Bacteria/*genetics ; Environment ; *Epigenesis, Genetic ; *Gene Expression ; *Gene Regulatory Networks ; Models, Genetic ; Phenotype ; Stochastic Processes ; }, abstract = {Measuring gene expression at the single cell and single molecule level has recently made possible the quantitative measurement of stochasticity of gene expression. This enables identification of the probable sources and roles of noise. Gene expression noise can result in bacterial population heterogeneity, offering specific advantages for fitness and survival in various environments. This trait is therefore selected during the evolution of the species, and is consequently regulated by a specific genetic network architecture. Examples exist in stress-response mechanisms, as well as in infection and pathogenicity strategies, pointing to advantages for multicellularity of bacterial populations.}, } @article {pmid28427501, year = {2017}, author = {Fonseca, NA and Cruz, AF and Moura, V and Simões, S and Moreira, JN}, title = {The cancer stem cell phenotype as a determinant factor of the heterotypic nature of breast tumors.}, journal = {Critical reviews in oncology/hematology}, volume = {113}, number = {}, pages = {111-121}, doi = {10.1016/j.critrevonc.2017.03.016}, pmid = {28427501}, issn = {1879-0461}, mesh = {Breast Neoplasms/metabolism/pathology/*physiopathology ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Neoplastic Stem Cells/*metabolism/physiology ; Neovascularization, Pathologic ; *Phosphoproteins ; *RNA-Binding Proteins ; *Signal Transduction ; *Tumor Microenvironment ; }, abstract = {Gathering evidence supports the existence of a population of cells with stem-like characteristics, named cancer stem cells (CSC), which is involved not only in tumor recurrence but also in tumorigenicity, metastization and drug resistance. Several markers have been used to identify putative CSC sub-populations in different cancers. Notwithstanding, it has been acknowledged that breast CSC may originate from non-stem cancer cells (non-SCC), interconverting through an epithelial-to-mesenchymal transition-mediated process, and presenting several deregulated canonical and developmental signaling pathways. These support the heterogeneity that, directly or indirectly, influences fundamental biological features supporting breast tumor development. Accordingly, CSC have increasingly become highly relevant cellular targets. In this review, we will address the stemness concept in cancer, setting the perspective on CSC and their origin, by exploring their relation and regulation within the tumor microenvironment, in the context of emerging therapeutic targets. Within this framework, we will discuss nucleolin, a protein that has been associated with angiogenesis and, more recently, with the stemness phenotype, becoming a common denominator between CSC and non-SCC for multicellular targeting.}, } @article {pmid28425150, year = {2017}, author = {Grochau-Wright, ZI and Hanschen, ER and Ferris, PJ and Hamaji, T and Nozaki, H and Olson, BJSC and Michod, RE}, title = {Genetic basis for soma is present in undifferentiated volvocine green algae.}, journal = {Journal of evolutionary biology}, volume = {30}, number = {6}, pages = {1205-1218}, pmid = {28425150}, issn = {1420-9101}, support = {NNX13AH41G//NASA/United States ; T32 GM084905/GM/NIGMS NIH HHS/United States ; NNX13AH41G//NASA/ ; }, mesh = {Adaptation, Physiological ; *Biological Evolution ; Chlorophyta ; *Phylogeny ; Stress, Physiological ; *Volvox ; }, abstract = {Somatic cellular differentiation plays a critical role in the transition from unicellular to multicellular life, but the evolution of its genetic basis remains poorly understood. By definition, somatic cells do not reproduce to pass on genes and so constitute an extreme form of altruistic behaviour. The volvocine green algae provide an excellent model system to study the evolution of multicellularity and somatic differentiation. In Volvox carteri, somatic cell differentiation is controlled by the regA gene, which is part of a tandem duplication of genes known as the reg cluster. Although previous work found the reg cluster in divergent Volvox species, its origin and distribution in the broader group of volvocine algae has not been known. Here, we show that the reg cluster is present in many species without somatic cells and determine that the genetic basis for soma arose before the phenotype at the origin of the family Volvocaceae approximately 200 million years ago. We hypothesize that the ancestral function was involved in regulating reproduction in response to stress and that this function was later co-opted to produce soma. Determining that the reg cluster was co-opted to control somatic cell development provides insight into how cellular differentiation, and with it greater levels of complexity and individuality, evolves.}, } @article {pmid28424311, year = {2017}, author = {Deora, T and Gundiah, N and Sane, SP}, title = {Mechanics of the thorax in flies.}, journal = {The Journal of experimental biology}, volume = {220}, number = {Pt 8}, pages = {1382-1395}, doi = {10.1242/jeb.128363}, pmid = {28424311}, issn = {1477-9145}, mesh = {Animals ; Biomechanical Phenomena ; Body Size ; Diptera/anatomy & histology/*physiology ; *Flight, Animal ; Wings, Animal/anatomy & histology/*physiology ; }, abstract = {Insects represent more than 60% of all multicellular life forms, and are easily among the most diverse and abundant organisms on earth. They evolved functional wings and the ability to fly, which enabled them to occupy diverse niches. Insects of the hyper-diverse orders show extreme miniaturization of their body size. The reduced body size, however, imposes steep constraints on flight ability, as their wings must flap faster to generate sufficient forces to stay aloft. Here, we discuss the various physiological and biomechanical adaptations of the thorax in flies which enabled them to overcome the myriad constraints of small body size, while ensuring very precise control of their wing motion. One such adaptation is the evolution of specialized myogenic or asynchronous muscles that power the high-frequency wing motion, in combination with neurogenic or synchronous steering muscles that control higher-order wing kinematic patterns. Additionally, passive cuticular linkages within the thorax coordinate fast and yet precise bilateral wing movement, in combination with an actively controlled clutch and gear system that enables flexible flight patterns. Thus, the study of thoracic biomechanics, along with the underlying sensory-motor processing, is central in understanding how the insect body form is adapted for flight.}, } @article {pmid28418331, year = {2017}, author = {Fidler, AL and Darris, CE and Chetyrkin, SV and Pedchenko, VK and Boudko, SP and Brown, KL and Gray Jerome, W and Hudson, JK and Rokas, A and Hudson, BG}, title = {Collagen IV and basement membrane at the evolutionary dawn of metazoan tissues.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {28418331}, issn = {2050-084X}, support = {T32 DK007569/DK/NIDDK NIH HHS/United States ; R24 DK103067/DK/NIDDK NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; R37 DK018381/DK/NIDDK NIH HHS/United States ; P30 DK114809/DK/NIDDK NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; R01 DK018381/DK/NIDDK NIH HHS/United States ; U2C DK059637/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Basement Membrane/*chemistry ; Collagen Type IV/*analysis/*genetics ; Ctenophora/cytology/genetics/metabolism/*physiology ; Evolution, Molecular ; Extracellular Matrix/*chemistry ; }, abstract = {The role of the cellular microenvironment in enabling metazoan tissue genesis remains obscure. Ctenophora has recently emerged as one of the earliest-branching extant animal phyla, providing a unique opportunity to explore the evolutionary role of the cellular microenvironment in tissue genesis. Here, we characterized the extracellular matrix (ECM), with a focus on collagen IV and its variant, spongin short-chain collagens, of non-bilaterian animal phyla. We identified basement membrane (BM) and collagen IV in Ctenophora, and show that the structural and genomic features of collagen IV are homologous to those of non-bilaterian animal phyla and Bilateria. Yet, ctenophore features are more diverse and distinct, expressing up to twenty genes compared to six in vertebrates. Moreover, collagen IV is absent in unicellular sister-groups. Collectively, we conclude that collagen IV and its variant, spongin, are primordial components of the extracellular microenvironment, and as a component of BM, collagen IV enabled the assembly of a fundamental architectural unit for multicellular tissue genesis.}, } @article {pmid28409312, year = {2017}, author = {Garcin, CL and Habib, SJ}, title = {A Comparative Perspective on Wnt/β-Catenin Signalling in Cell Fate Determination.}, journal = {Results and problems in cell differentiation}, volume = {61}, number = {}, pages = {323-350}, doi = {10.1007/978-3-319-53150-2_15}, pmid = {28409312}, issn = {0080-1844}, mesh = {Animals ; Body Patterning/physiology ; Cell Differentiation/*physiology ; Embryonic Development/*physiology ; Humans ; Wnt Signaling Pathway/*physiology ; }, abstract = {The Wnt/β-catenin pathway is an ancient and highly conserved signalling pathway that plays fundamental roles in the regulation of embryonic development and adult homeostasis. This pathway has been implicated in numerous cellular processes, including cell proliferation, differentiation, migration, morphological changes and apoptosis. In this chapter, we aim to illustrate with specific examples the involvement of Wnt/β-catenin signalling in cell fate determination. We discuss the roles of the Wnt/β-catenin pathway in specifying cell fate throughout evolution, how its function in patterning during development is often reactivated during regeneration and how perturbation of this pathway has negative consequences for the control of cell fate.The origin of all life was a single cell that had the capacity to respond to cues from the environment. With evolution, multicellular organisms emerged, and as a result, subsets of cells arose to form tissues able to respond to specific instructive signals and perform specialised functions. This complexity and specialisation required two types of messages to direct cell fate: intra- and intercellular. A fundamental question in developmental biology is to understand the underlying mechanisms of cell fate choice. Amongst the numerous external cues involved in the generation of cellular diversity, a prominent pathway is the Wnt signalling pathway in all its forms.}, } @article {pmid28406446, year = {2017}, author = {Breviario, D}, title = {Is There any Alternative to Canonical DNA Barcoding of Multicellular Eukaryotic Species? A Case for the Tubulin Gene Family.}, journal = {International journal of molecular sciences}, volume = {18}, number = {4}, pages = {}, pmid = {28406446}, issn = {1422-0067}, mesh = {DNA/chemistry/metabolism ; *DNA Barcoding, Taxonomic ; Eukaryota/*genetics ; Polymorphism, Genetic ; Sequence Analysis, DNA ; Tubulin/*genetics ; }, abstract = {Modern taxonomy is largely relying on DNA barcoding, a nucleotide sequence-based approach that provides automated species identification using short orthologous DNA regions, mainly of organellar origin when applied to multicellular Eukaryotic species. Target DNA loci have been selected that contain a minimal amount of nucleotide sequence variation within species while diverging among species. This strategy is quite effective for the identification of vertebrates and other animal lineages but poses a problem in plants where different combinations of two or three loci are constantly used. Even so, species discrimination in such plant categories as ornamentals and herbals remain problematic as well as the confident identification of subspecies, ecotypes, and closely related or recently evolved species. All these limitations may be successfully solved by the application of a different strategy, based on the use of a multi-locus, ubiquitous, nuclear marker, that is tubulin. In fact, the tubulin-based polymorphism method can release specific genomic profiles to any plant species independently from its taxonomic group. This offers the rare possibility of an effective yet generic genomic fingerprint. In a more general context, the issue is raised about the possibility that approaches alternative to systematic DNA sequencing may still provide useful and simple solutions.}, } @article {pmid28405374, year = {2017}, author = {Pratlong, M and Haguenauer, A and Chenesseau, S and Brener, K and Mitta, G and Toulza, E and Bonabaud, M and Rialle, S and Aurelle, D and Pontarotti, P}, title = {Evidence for a genetic sex determination in Cnidaria, the Mediterranean red coral (Corallium rubrum).}, journal = {Royal Society open science}, volume = {4}, number = {3}, pages = {160880}, pmid = {28405374}, issn = {2054-5703}, abstract = {Sexual reproduction is widespread among eukaryotes, and the sex-determining processes vary greatly among species. While genetic sex determination (GSD) has been intensively described in bilaterian species, no example has yet been recorded among non-bilaterians. However, the quasi-ubiquitous repartition of GSD among multicellular species suggests that similar evolutionary forces can promote this system, and that these forces could occur also in non-bilaterians. Studying sex determination across the range of Metazoan diversity is indeed important to understand better the evolution of this mechanism and its lability. We tested the existence of sex-linked genes in the gonochoric red coral (Corallium rubrum, Cnidaria) using restriction site-associated DNA sequencing. We analysed 27 461 single nucleotide polymorphisms (SNPs) in 354 individuals from 12 populations including 53 that were morphologically sexed. We found a strong association between the allele frequencies of 472 SNPs and the sex of individuals, suggesting an XX/XY sex-determination system. This result was confirmed by the identification of 435 male-specific loci. An independent test confirmed that the amplification of these loci enabled us to identify males with absolute certainty. This is the first demonstration of a GSD system among non-bilaterian species and a new example of its convergence in multicellular eukaryotes.}, } @article {pmid28398223, year = {2017}, author = {Cao, TJ and Huang, XQ and Qu, YY and Zhuang, Z and Deng, YY and Lu, S}, title = {Cloning and Functional Characterization of a Lycopene β-Cyclase from Macrophytic Red Alga Bangia fuscopurpurea.}, journal = {Marine drugs}, volume = {15}, number = {4}, pages = {}, pmid = {28398223}, issn = {1660-3397}, mesh = {Amino Acid Sequence ; Base Sequence ; Carotenoids/*genetics/*metabolism ; Cloning, Molecular/methods ; Escherichia coli/genetics ; Intramolecular Lyases/*genetics/*metabolism ; Lycopene ; Photosynthesis/physiology ; Phylogeny ; Rhodophyta/*genetics/*metabolism ; Zeaxanthins/genetics/metabolism ; beta Carotene/genetics/metabolism ; }, abstract = {Lycopene cyclases cyclize the open ends of acyclic lycopene (ψ,ψ-carotene) into β- or ε-ionone rings in the crucial bifurcation step of carotenoid biosynthesis. Among all carotenoid constituents, β-carotene (β,β-carotene) is found in all photosynthetic organisms, except for purple bacteria and heliobacteria, suggesting a ubiquitous distribution of lycopene β-cyclase activity in these organisms. In this work, we isolated a gene (BfLCYB) encoding a lycopene β-cyclase from Bangia fuscopurpurea, a red alga that is considered to be one of the primitive multicellular eukaryotic photosynthetic organisms and accumulates carotenoid constituents with both β- and ε-rings, including β-carotene, zeaxanthin, α-carotene (β,ε-carotene) and lutein. Functional complementation in Escherichia coli demonstrated that BfLCYB is able to catalyze cyclization of lycopene into monocyclic γ-carotene (β,ψ-carotene) and bicyclic β-carotene, and cyclization of the open end of monocyclic δ-carotene (ε,ψ-carotene) to produce α-carotene. No ε-cyclization activity was identified for BfLCYB. Sequence comparison showed that BfLCYB shares conserved domains with other functionally characterized lycopene cyclases from different organisms and belongs to a group of ancient lycopene cyclases. Although B. fuscopurpurea also synthesizes α-carotene and lutein, its enzyme-catalyzing ε-cyclization is still unknown.}, } @article {pmid28395144, year = {2017}, author = {Gaiti, F and Jindrich, K and Fernandez-Valverde, SL and Roper, KE and Degnan, BM and Tanurdžić, M}, title = {Landscape of histone modifications in a sponge reveals the origin of animal cis-regulatory complexity.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {28395144}, issn = {2050-084X}, mesh = {Animals ; *Biological Evolution ; *Gene Expression Regulation ; *Histone Code ; Porifera/*genetics ; }, abstract = {Combinatorial patterns of histone modifications regulate developmental and cell type-specific gene expression and underpin animal complexity, but it is unclear when this regulatory system evolved. By analysing histone modifications in a morphologically-simple, early branching animal, the sponge Amphimedonqueenslandica, we show that the regulatory landscape used by complex bilaterians was already in place at the dawn of animal multicellularity. This includes distal enhancers, repressive chromatin and transcriptional units marked by H3K4me3 that vary with levels of developmental regulation. Strikingly, Amphimedon enhancers are enriched in metazoan-specific microsyntenic units, suggesting that their genomic location is extremely ancient and likely to place constraints on the evolution of surrounding genes. These results suggest that the regulatory foundation for spatiotemporal gene expression evolved prior to the divergence of sponges and eumetazoans, and was necessary for the evolution of animal multicellularity.}, } @article {pmid28392224, year = {2017}, author = {Schiffmann, Y}, title = {The non-equilibrium basis of Turing Instability and localised biological work.}, journal = {Progress in biophysics and molecular biology}, volume = {127}, number = {}, pages = {12-32}, doi = {10.1016/j.pbiomolbio.2017.04.002}, pmid = {28392224}, issn = {1873-1732}, mesh = {Adenosine Triphosphate/metabolism ; Animals ; *Biological Evolution ; Humans ; Hydrolysis ; *Models, Biological ; }, abstract = {Turing's theory for biological pattern formation is based on the instability of the homogeneous state, which occurs if certain key criteria are met. The problem of how chemical energy is converted to localised biological work requires one to understand not only the basis of localised power generation, but also the age-old puzzle of how organisms decrease their entropy; these problems can only be solved by the identification of the Turing Instability. At the heart of this is how natural selection, not chemistry, has fashioned the large non-equilibrium overall affinity (ΔG is a large negative quantity) for the oxidation of the fuel molecules. Natural selection has also resulted in the homeostasis at non-equilibrium values of the hydrolysis of molecules like ATP, GTP, which are the energy links between the overall oxidation of the fuel and biological work. The conditions for such homeostasis are central requirements for the Turing Instability and are the essence of being alive. The Turing-Child (TC) patterns are the spontaneous primary spatial cause not only of localised biological work in multicellular systems (especially those in patterning and development) but also of intracellular patterns including the mitotic spindle and the contractile ring. The Turing picture comprises the nonuniform distribution of the concentrations of the Turing morphogens, cAMP and ATP, and the Child picture is the resulting nonuniform distribution of the metabolic rate and of power. The TC pattern is shaped as the dominant eigenfunction in the combination of eigenfunctions which provides the spatial pattern of the Turing morphogens. The TC patterns and the bifurcation parameter manifest quantisation and symmetry as in music and in applications of quantum mechanics. The notion of correlation diagrams is also introduced.}, } @article {pmid28386213, year = {2017}, author = {Levy, E}, title = {Exosomes in the Diseased Brain: First Insights from In vivo Studies.}, journal = {Frontiers in neuroscience}, volume = {11}, number = {}, pages = {142}, pmid = {28386213}, issn = {1662-4548}, support = {P01 AG017617/AG/NIA NIH HHS/United States ; }, abstract = {Extracellular vesicles (EVs) are nanoscale size vesicles secreted by cells and are important mediators of intercellular communication and genetic exchange. Exosomes, EVs generated in endosomal multivesicular bodies, have been the focus of numerous publications as they have emerged as clinically valuable markers of disease states. Exosomes have been mostly studied from conditioned culture media and body fluids, with the difficulty of isolating exosomes from tissues having delayed their study in vivo. The implementation of a method designed to isolate exosomes from tissues, however, has yielded the first insights into characteristics of exosomes in the brain. It has been observed that brain exosomes from murine models of neurodegenerative diseases and human postmortem brains tend to mirror the protein content of the cells of origin, and interestingly, they are enriched with toxic proteins. Whether this enrichment with neurotoxic proteins is beneficial by relieving neurons of accumulated toxic material or detrimental to the brain by propagating pathogenicity throughout the brain remains to be answered. Here is summarized the first group of studies describing exosomes isolated from brain, results that demonstrate that exosomes in vivo reflect complex multicellular pathogenic processes in neurodegenerative disorders and the brain's response to injury and damage.}, } @article {pmid28384293, year = {2017}, author = {Olariu, V and Nilsson, J and Jönsson, H and Peterson, C}, title = {Different reprogramming propensities in plants and mammals: Are small variations in the core network wirings responsible?.}, journal = {PloS one}, volume = {12}, number = {4}, pages = {e0175251}, pmid = {28384293}, issn = {1932-6203}, mesh = {Animals ; Mammals/*physiology ; Mice ; *Plant Physiological Phenomena ; }, abstract = {Although the plant and animal kingdoms were separated more than 1,6 billion years ago, multicellular development is for both guided by similar transcriptional, epigenetic and posttranscriptional machinery. One may ask to what extent there are similarities and differences in the gene regulation circuits and their dynamics when it comes to important processes like stem cell regulation. The key players in mouse embryonic stem cells governing pluripotency versus differentiation are Oct4, Sox2 and Nanog. Correspondingly, the WUSCHEL and CLAVATA3 genes represent a core in the Shoot Apical Meristem regulation for plants. In addition, both systems have designated genes that turn on differentiation. There is very little molecular homology between mammals and plants for these core regulators. Here, we focus on functional homologies by performing a comparison between the circuitry connecting these players in plants and animals and find striking similarities, suggesting that comparable regulatory logics have been evolved for stem cell regulation in both kingdoms. From in silico simulations we find similar differentiation dynamics. Further when in the differentiated state, the cells are capable of regaining the stem cell state. We find that the propensity for this is higher for plants as compared to mammalians. Our investigation suggests that, despite similarity in core regulatory networks, the dynamics of these can contribute to plant cells being more plastic than mammalian cells, i.e. capable to reorganize from single differentiated cells to whole plants-reprogramming. The presence of an incoherent feed-forward loop in the mammalian core circuitry could be the origin of the different reprogramming behaviour.}, } @article {pmid28383827, year = {2017}, author = {Palazzo, L and Mikoč, A and Ahel, I}, title = {ADP-ribosylation: new facets of an ancient modification.}, journal = {The FEBS journal}, volume = {284}, number = {18}, pages = {2932-2946}, pmid = {28383827}, issn = {1742-4658}, support = {/WT_/Wellcome Trust/United Kingdom ; 101794/WT_/Wellcome Trust/United Kingdom ; 281739/ERC_/European Research Council/International ; C35050/A22284/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {ADP Ribose Transferases/*genetics/metabolism ; Aging/genetics/*metabolism ; Animals ; Archaea/genetics/metabolism ; Bacteria/genetics/metabolism ; Biological Evolution ; DNA Damage ; *DNA Repair ; DNA Replication ; Gene Expression ; Humans ; Isoenzymes/genetics/metabolism ; Phosphoric Diester Hydrolases/genetics/metabolism ; Poly Adenosine Diphosphate Ribose/*metabolism ; *Protein Processing, Post-Translational ; Pyrophosphatases/genetics/metabolism ; Signal Transduction ; Viruses/genetics/metabolism ; }, abstract = {Rapid response to environmental changes is achieved by uni- and multicellular organisms through a series of molecular events, often involving modification of macromolecules, including proteins, nucleic acids and lipids. Amongst these, ADP-ribosylation is of emerging interest because of its ability to modify different macromolecules in the cells, and its association with many key biological processes, such as DNA-damage repair, DNA replication, transcription, cell division, signal transduction, stress and infection responses, microbial pathogenicity and aging. In this review, we provide an update on novel pathways and mechanisms regulated by ADP-ribosylation in organisms coming from all kingdoms of life.}, } @article {pmid28368386, year = {2017}, author = {Barber, J}, title = {A mechanism for water splitting and oxygen production in photosynthesis.}, journal = {Nature plants}, volume = {3}, number = {}, pages = {17041}, doi = {10.1038/nplants.2017.41}, pmid = {28368386}, issn = {2055-0278}, mesh = {Biological Evolution ; Models, Biological ; Oxidation-Reduction ; Oxygen/*metabolism ; *Photosynthesis ; Photosystem II Protein Complex/*chemistry ; Plants/*metabolism ; Water/*metabolism ; }, abstract = {Sunlight is absorbed and converted to chemical energy by photosynthetic organisms. At the heart of this process is the most fundamental reaction on Earth, the light-driven splitting of water into its elemental constituents. In this way molecular oxygen is released, maintaining an aerobic atmosphere and creating the ozone layer. The hydrogen that is released is used to convert carbon dioxide into the organic molecules that constitute life and were the origin of fossil fuels. Oxidation of these organic molecules, either by respiration or combustion, leads to the recombination of the stored hydrogen with oxygen, releasing energy and reforming water. This water splitting is achieved by the enzyme photosystem II (PSII). Its appearance at least 3 billion years ago, and linkage through an electron transfer chain to photosystem I, directly led to the emergence of eukaryotic and multicellular organisms. Before this, biological organisms had been dependent on hydrogen/electron donors, such as H2S, NH3, organic acids and Fe[2+], that were in limited supply compared with the oceans of liquid water. However, it is likely that water was also used as a hydrogen source before the emergence of PSII, as found today in anaerobic prokaryotic organisms that use carbon monoxide as an energy source to split water. The enzyme that catalyses this reaction is carbon monoxide dehydrogenase (CODH). Similarities between PSII and the iron- and nickel-containing form of this enzyme (Fe-Ni CODH) suggest a possible mechanism for the photosynthetic O-O bond formation.}, } @article {pmid28360330, year = {2017}, author = {Soo, RM and Hemp, J and Parks, DH and Fischer, WW and Hugenholtz, P}, title = {On the origins of oxygenic photosynthesis and aerobic respiration in Cyanobacteria.}, journal = {Science (New York, N.Y.)}, volume = {355}, number = {6332}, pages = {1436-1440}, doi = {10.1126/science.aal3794}, pmid = {28360330}, issn = {1095-9203}, mesh = {Aerobiosis ; Bacterial Proteins/classification/genetics/*metabolism ; Biological Evolution ; Cyanobacteria/classification/*enzymology/genetics ; Electron Transport Complex III/classification/genetics/*metabolism ; Electron Transport Complex IV/genetics/*metabolism ; Genome, Bacterial ; Oxygen/*metabolism ; Photosynthesis/genetics/*physiology ; Phylogeny ; }, abstract = {The origin of oxygenic photosynthesis in Cyanobacteria led to the rise of oxygen on Earth ~2.3 billion years ago, profoundly altering the course of evolution by facilitating the development of aerobic respiration and complex multicellular life. Here we report the genomes of 41 uncultured organisms related to the photosynthetic Cyanobacteria (class Oxyphotobacteria), including members of the class Melainabacteria and a new class of Cyanobacteria (class Sericytochromatia) that is basal to the Melainabacteria and Oxyphotobacteria All members of the Melainabacteria and Sericytochromatia lack photosynthetic machinery, indicating that phototrophy was not an ancestral feature of the Cyanobacteria and that Oxyphotobacteria acquired the genes for photosynthesis relatively late in cyanobacterial evolution. We show that all three classes independently acquired aerobic respiratory complexes, supporting the hypothesis that aerobic respiration evolved after oxygenic photosynthesis.}, } @article {pmid28359330, year = {2017}, author = {Szafranski, P}, title = {Evolutionarily recent, insertional fission of mitochondrial cox2 into complementary genes in bilaterian Metazoa.}, journal = {BMC genomics}, volume = {18}, number = {1}, pages = {269}, pmid = {28359330}, issn = {1471-2164}, mesh = {Animals ; Electron Transport Complex IV/chemistry/*genetics ; *Evolution, Molecular ; Gene Expression Regulation ; *Genes, Mitochondrial ; Genome, Mitochondrial ; Hydrophobic and Hydrophilic Interactions ; Mitochondrial Dynamics/*genetics ; *Mutagenesis, Insertional ; Phylogeny ; Polyadenylation ; }, abstract = {BACKGROUND: Mitochondrial genomes (mtDNA) of multicellular animals (Metazoa) with bilateral symmetry (Bilateria) are compact and usually carry 13 protein-coding genes for subunits of three respiratory complexes and ATP synthase. However, occasionally reported exceptions to this typical mtDNA organization prompted speculation that, as in protists and plants, some bilaterian mitogenomes may continue to lose their canonical genes, or may even acquire new genes. To shed more light on this phenomenon, a PCR-based screen was conducted to assess fast-evolving mtDNAs of apocritan Hymenoptera (Arthropoda, Insecta) for genomic rearrangements that might be associated with the modification of mitochondrial gene content.

RESULTS: Sequencing of segmental inversions, identified in the screen, revealed that the cytochrome oxidase subunit II gene (cox2) of Campsomeris (Dielis) (Scoliidae) was split into two genes coding for COXIIA and COXIIB. The COXII-derived complementary polypeptides apparently form a heterodimer, have reduced hydrophobicity compared with the majority of mitogenome-encoded COX subunits, and one of them, COXIIB, features increased content of Cys residues. Analogous cox2 fragmentation is known only in two clades of protists (chlorophycean algae and alveolates), where it has been associated with piecewise relocation of this gene into the nucleus. In Campsomeris mtDNA, cox2a and cox2b loci are separated by a 3-kb large cluster of several antiparallel overlapping ORFs, one of which, qnu, seems to encode a nuclease that may have played a role in cox2 fission.

CONCLUSIONS: Although discontinuous mitochondrial protein genes encoding fragmented, complementary polypeptides are known in protists and some plants, split cox2 of Campsomeris is the first case of such a gene arrangement found in animals. The reported data also indicate that bilaterian animal mitogenomes may be carrying lineage-specific genes more often than previously thought, and suggest a homing endonuclease-based mechanism for insertional mitochondrial gene fission.}, } @article {pmid28357395, year = {2017}, author = {Mignot, T and Nöllmann, M}, title = {New insights into the function of a versatile class of membrane molecular motors from studies of Myxococcus xanthus surface (gliding) motility.}, journal = {Microbial cell (Graz, Austria)}, volume = {4}, number = {3}, pages = {98-100}, doi = {10.15698/mic2017.03.563}, pmid = {28357395}, issn = {2311-2638}, abstract = {Cell motility is a central function of living cells, as it empowers colonization of new environmental niches, cooperation, and development of multicellular organisms. This process is achieved by complex yet precise energy-consuming machineries in both eukaryotes and bacteria. Bacteria move on surfaces using extracellular appendages such as flagella and pili but also by a less-understood process called gliding motility. During this process, rod-shaped bacteria move smoothly along their long axis without any visible morphological changes besides occasional bending. For this reason, the molecular mechanism of gliding motility and its origin have long remained a complete mystery. An important breakthrough in the understanding of gliding motility came from single cell and genetic studies in the delta-proteobacterium Myxococcus xanthus. These early studies revealed, for the first time, the existence of bacterial Focal Adhesion complexes (FA). FAs are formed at the bacterial pole and rapidly move towards the opposite cell pole. Their attachment to the underlying surface is linked to cell propulsion, in a process similar to the rearward translocation of actomyosin complexes in Apicomplexans. The protein machinery that forms at FAs was shown to contain up to seventeen proteins predicted to localize in all layers of the bacterial cell envelope, the cytosolic face, the inner membrane (IM), the periplasmic space and the outer membrane (OM). Among these proteins, a proton-gated channel at the inner membrane was identified as the molecular motor. Thus, thrust generation requires the transduction of traction forces generated at the inner membrane through the cell envelope beyond the rigid barrier of the bacterial peptidoglycan.}, } @article {pmid28355288, year = {2017}, author = {Werfel, J and Ingber, DE and Bar-Yam, Y}, title = {Theory and associated phenomenology for intrinsic mortality arising from natural selection.}, journal = {PloS one}, volume = {12}, number = {3}, pages = {e0173677}, pmid = {28355288}, issn = {1932-6203}, mesh = {Aging/*physiology ; Animals ; Biological Evolution ; Herbivory/physiology ; Host-Pathogen Interactions ; Longevity/*physiology ; *Models, Biological ; *Models, Statistical ; Plants ; Poaceae/physiology ; Predatory Behavior/physiology ; Reproduction/physiology ; Selection, Genetic/*physiology ; }, abstract = {Standard evolutionary theories of aging and mortality, implicitly based on assumptions of spatial averaging, hold that natural selection cannot favor shorter lifespan without direct compensating benefit to individual reproductive success. However, a number of empirical observations appear as exceptions to or are difficult to reconcile with this view, suggesting explicit lifespan control or programmed death mechanisms inconsistent with the classic understanding. Moreover, evolutionary models that take into account the spatial distributions of populations have been shown to exhibit a variety of self-limiting behaviors, maintained through environmental feedback. Here we extend recent work on spatial modeling of lifespan evolution, showing that both theory and phenomenology are consistent with programmed death. Spatial models show that self-limited lifespan robustly results in long-term benefit to a lineage; longer-lived variants may have a reproductive advantage for many generations, but shorter lifespan ultimately confers long-term reproductive advantage through environmental feedback acting on much longer time scales. Numerous model variations produce the same qualitative result, demonstrating insensitivity to detailed assumptions; the key conditions under which self-limited lifespan is favored are spatial extent and locally exhaustible resources. Factors including lower resource availability, higher consumption, and lower dispersal range are associated with evolution of shorter lifespan. A variety of empirical observations can parsimoniously be explained in terms of long-term selective advantage for intrinsic mortality. Classically anomalous empirical data on natural lifespans and intrinsic mortality, including observations of longer lifespan associated with increased predation, and evidence of programmed death in both unicellular and multicellular organisms, are consistent with specific model predictions. The generic nature of the spatial model conditions under which intrinsic mortality is favored suggests a firm theoretical basis for the idea that evolution can quite generally select for shorter lifespan directly.}, } @article {pmid28342854, year = {2017}, author = {Holzer, G and Roux, N and Laudet, V}, title = {Evolution of ligands, receptors and metabolizing enzymes of thyroid signaling.}, journal = {Molecular and cellular endocrinology}, volume = {459}, number = {}, pages = {5-13}, doi = {10.1016/j.mce.2017.03.021}, pmid = {28342854}, issn = {1872-8057}, mesh = {Animals ; Biological Evolution ; Cnidaria/anatomy & histology/physiology ; Gene Expression Regulation, Developmental ; Humans ; Insecta/anatomy & histology/physiology ; Iodide Peroxidase/genetics/*metabolism ; Ligands ; Phylogeny ; Receptors, Thyroid Hormone/genetics/*metabolism ; Signal Transduction/*physiology ; Species Specificity ; Thyroid Gland/*physiology ; Thyroxine/genetics/*metabolism ; Triiodothyronine/analogs & derivatives/genetics/*metabolism ; }, abstract = {Thyroid hormones (THs) play important roles in vertebrates such as the control of the metabolism, development and seasonality. Given the pleiotropic effects of thyroid disorders (developmental delay, mood disorder, tachycardia, etc), THs signaling is highly investigated, specially using mammalian models. In addition, the critical role of TH in controlling frog metamorphosis has led to the use of Xenopus as another prominent model to study THs action. Nevertheless, animals regarded as non-model species can also improve our understanding of THs signaling. For instance, studies in amphioxus highlighted the role of Triac as a bona fide thyroid hormone receptor (TR) ligand. In this review, we discuss our current understanding of the THs signaling in the different taxa forming the metazoans (multicellular animals) group. We mainly focus on three actors of the THs signaling: the ligand, the receptor and the deiodinases, enzymes playing a critical role in THs metabolism. By doing so, we also pinpoint many key questions that remain unanswered. How can THs accelerate metamorphosis in tunicates and echinoderms while their TRs have not been yet demonstrated as functional THs receptors in these species? Do THs have a biological effect in insects and cnidarians even though they do not have any TR? What is the basic function of THs in invertebrate protostomia? These questions can appear disconnected from pharmacological issues and human applications, but the investigation of THs signaling at the metazoans scale can greatly improve our understanding of this major endocrinological pathway.}, } @article {pmid28324731, year = {2017}, author = {Jayadev, R and Sherwood, DR}, title = {Basement membranes.}, journal = {Current biology : CB}, volume = {27}, number = {6}, pages = {R207-R211}, doi = {10.1016/j.cub.2017.02.006}, pmid = {28324731}, issn = {1879-0445}, support = {R01 GM079320/GM/NIGMS NIH HHS/United States ; R01 GM100083/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Basement Membrane/*physiology ; Caenorhabditis elegans/growth & development/*physiology ; Disease Susceptibility/*physiopathology ; Drosophila/growth & development/*physiology ; Growth/physiology ; Homeostasis/physiology ; Humans ; Mice ; }, abstract = {Basement membranes (BMs) are thin, dense sheets of specialized, self-assembled extracellular matrix that surround most animal tissues (Figure 1, top). The emergence of BMs coincided with the origin of multicellularity in animals, suggesting that they were essential for the formation of tissues. Their sheet-like structure derives from two independent polymeric networks - one of laminin and one of type IV collagen (Figure 1, bottom). These independent collagen and laminin networks are thought to be linked by several additional extracellular matrix proteins, including nidogen and perlecan (Figure 1, bottom). BMs are usually associated with cells and are anchored to cell surfaces through interactions with adhesion receptors and sulfated glycolipids (Figure 1, bottom). Various combinations of other proteins, glycoproteins, and proteoglycans - including fibulin, hemicentin, SPARC, agrin, and type XVIII collagen - are present in BMs, creating biochemically and biophysically distinct structures that serve a wide variety of functions. BMs have traditionally been viewed as static protein assemblies that provide structural support to tissues. However, recent studies have begun to uncover dynamic, active roles for BMs in many developmental processes. Here, we discuss established and emerging roles of BMs in development, tissue construction, and tissue homeostasis. We also explore how cells traverse BM barriers, the roles of BMs in human diseases, and future directions for the field.}, } @article {pmid28317949, year = {2017}, author = {Rudd, TR and Preston, MD and Yates, EA}, title = {The nature of the conserved basic amino acid sequences found among 437 heparin binding proteins determined by network analysis.}, journal = {Molecular bioSystems}, volume = {13}, number = {5}, pages = {852-865}, doi = {10.1039/c6mb00857g}, pmid = {28317949}, issn = {1742-2051}, mesh = {Amino Acid Sequence ; Binding Sites ; Computational Biology/methods ; Conserved Sequence ; Heparin/*metabolism ; Heparitin Sulfate/*metabolism ; Humans ; Models, Molecular ; Protein Binding ; Protein Interaction Maps ; Proteins/*chemistry/*metabolism ; }, abstract = {In multicellular organisms, a large number of proteins interact with the polyanionic polysaccharides heparan sulphate (HS) and heparin. These interactions are usually assumed to be dominated by charge-charge interactions between the anionic carboxylate and/or sulfate groups of the polysaccharide and cationic amino acids of the protein. A major question is whether there exist conserved amino acid sequences for HS/heparin binding among these diverse proteins. Potentially conserved HS/heparin binding sequences were sought amongst 437 HS/heparin binding proteins. Amino acid sequences were extracted and compared using a Levenshtein distance metric. The resultant similarity matrices were visualised as graphs, enabling extraction of strongly conserved sequences from highly variable primary sequences while excluding short, core regions. This approach did not reveal extensive, conserved HS/heparin binding sequences, rather a number of shorter, more widely spaced sequences that may work in unison to form heparin-binding sites on protein surfaces, arguing for convergent evolution. Thus, it is the three-dimensional arrangement of these conserved motifs on the protein surface, rather than the primary sequence per se, which are the evolutionary elements.}, } @article {pmid28294448, year = {2017}, author = {Inglis, RF and Ryu, E and Asikhia, O and Strassmann, JE and Queller, DC}, title = {Does high relatedness promote cheater-free multicellularity in synthetic lifecycles?.}, journal = {Journal of evolutionary biology}, volume = {30}, number = {5}, pages = {985-993}, doi = {10.1111/jeb.13067}, pmid = {28294448}, issn = {1420-9101}, mesh = {*Biological Evolution ; Dictyostelium/*growth & development ; *Life Cycle Stages ; }, abstract = {The evolution of multicellularity is one of the key transitions in evolution and requires extreme levels of cooperation between cells. However, even when cells are genetically identical, noncooperative cheating mutants can arise that cause a breakdown in cooperation. How then, do multicellular organisms maintain cooperation between cells? A number of mechanisms that increase relatedness amongst cooperative cells have been implicated in the maintenance of cooperative multicellularity including single-cell bottlenecks and kin recognition. In this study, we explore how relatively simple biological processes such as growth and dispersal can act to increase relatedness and promote multicellular cooperation. Using experimental populations of pseudo-organisms, we found that manipulating growth and dispersal of clones of a social amoeba to create high levels of relatedness was sufficient to prevent the spread of cheating mutants. By contrast, cheaters were able to spread under low-relatedness conditions. Most surprisingly, we saw the largest increase in cheating mutants under an experimental treatment that should create intermediate levels of relatedness. This is because one of the factors raising relatedness, structured growth, also causes high vulnerability to growth rate cheaters.}, } @article {pmid28291791, year = {2017}, author = {Bengtson, S and Sallstedt, T and Belivanova, V and Whitehouse, M}, title = {Three-dimensional preservation of cellular and subcellular structures suggests 1.6 billion-year-old crown-group red algae.}, journal = {PLoS biology}, volume = {15}, number = {3}, pages = {e2000735}, pmid = {28291791}, issn = {1545-7885}, mesh = {*Fossils ; Geologic Sediments ; *Geological Phenomena ; India ; Phylogeny ; Radiometry ; Rhodophyta/*cytology/ultrastructure ; Subcellular Fractions/metabolism ; Time Factors ; }, abstract = {The ~1.6 Ga Tirohan Dolomite of the Lower Vindhyan in central India contains phosphatized stromatolitic microbialites. We report from there uniquely well-preserved fossils interpreted as probable crown-group rhodophytes (red algae). The filamentous form Rafatazmia chitrakootensis n. gen, n. sp. has uniserial rows of large cells and grows through diffusely distributed septation. Each cell has a centrally suspended, conspicuous rhomboidal disk interpreted as a pyrenoid. The septa between the cells have central structures that may represent pit connections and pit plugs. Another filamentous form, Denaricion mendax n. gen., n. sp., has coin-like cells reminiscent of those in large sulfur-oxidizing bacteria but much more recalcitrant than the liquid-vacuole-filled cells of the latter. There are also resemblances with oscillatoriacean cyanobacteria, although cell volumes in the latter are much smaller. The wider affinities of Denaricion are uncertain. Ramathallus lobatus n. gen., n. sp. is a lobate sessile alga with pseudoparenchymatous thallus, "cell fountains," and apical growth, suggesting florideophycean affinity. If these inferences are correct, Rafatazmia and Ramathallus represent crown-group multicellular rhodophytes, antedating the oldest previously accepted red alga in the fossil record by about 400 million years.}, } @article {pmid28284906, year = {2017}, author = {Lochab, AK and Extavour, CG}, title = {Bone Morphogenetic Protein (BMP) signaling in animal reproductive system development and function.}, journal = {Developmental biology}, volume = {427}, number = {2}, pages = {258-269}, doi = {10.1016/j.ydbio.2017.03.002}, pmid = {28284906}, issn = {1095-564X}, mesh = {Animals ; *Biological Evolution ; Bone Morphogenetic Proteins/*metabolism ; Cell Lineage ; Genitalia/embryology/*metabolism ; *Germ Cells/metabolism ; Humans ; Reproduction ; Signal Transduction ; }, abstract = {In multicellular organisms, the specification, maintenance, and transmission of the germ cell lineage to subsequent generations are critical processes that ensure species survival. A number of studies suggest that the Bone Morphogenetic Protein (BMP) pathway plays multiple roles in this cell lineage. We wished to use a comparative framework to examine the role of BMP signaling in regulating these processes, to determine if patterns would emerge that might shed light on the evolution of molecular mechanisms that may play germ cell-specific or other reproductive roles across species. To this end, here we review evidence to date from the literature supporting a role for BMP signaling in reproductive processes across Metazoa. We focus on germ line-specific processes, and separately consider somatic reproductive processes. We find that from primordial germ cell (PGC) induction to maintenance of PGC identity and gametogenesis, BMP signaling regulates these processes throughout embryonic development and adult life in multiple deuterostome and protostome clades. In well-studied model organisms, functional genetic evidence suggests that BMP signaling is required in the germ line across all life stages, with the exception of PGC specification in species that do not use inductive signaling to induce germ cell formation. The current evidence is consistent with the hypothesis that BMP signaling is ancestral in bilaterian inductive PGC specification. While BMP4 appears to be the most broadly employed ligand for the reproductive processes considered herein, we also noted evidence for sex-specific usage of different BMP ligands. In gametogenesis, BMP6 and BMP15 seem to have roles restricted to oogenesis, while BMP8 is restricted to spermatogenesis. We hypothesize that a BMP-based mechanism may have been recruited early in metazoan evolution to specify the germ line, and was subsequently co-opted for use in other germ line-specific and somatic reproductive processes. We suggest that if future studies assessing the function of the BMP pathway across extant species were to include a reproductive focus, that we would be likely to find continued evidence in favor of an ancient association between BMP signaling and the reproductive cell lineage in animals.}, } @article {pmid28258564, year = {2017}, author = {Ishibashi, K and Morishita, Y and Tanaka, Y}, title = {The Evolutionary Aspects of Aquaporin Family.}, journal = {Advances in experimental medicine and biology}, volume = {969}, number = {}, pages = {35-50}, doi = {10.1007/978-94-024-1057-0_2}, pmid = {28258564}, issn = {0065-2598}, mesh = {Amino Acid Sequence ; Animals ; Aquaporins/chemistry/classification/*genetics/metabolism ; Biological Evolution ; Biological Transport ; Conserved Sequence ; Fungi/classification/*genetics/metabolism ; Gene Duplication ; Gene Expression ; Gene Transfer, Horizontal ; Invertebrates/classification/*genetics/metabolism ; Phylogeny ; Plants/classification/*genetics/metabolism ; Prokaryotic Cells/classification/*metabolism ; Protein Domains ; Vertebrates/classification/*genetics/metabolism ; }, abstract = {Aquaporins (AQPs) are a family of transmembrane proteins present in almost all species including virus. They are grossly divided into three subfamilies based on the sequence around a highly conserved pore-forming NPA motif: (1) classical water -selective AQP (CAQP), (2) glycerol -permeable aquaglyceroporin (AQGP) and (3) AQP super-gene channel, superaquaporin (SAQP). AQP is composed of two tandem repeats of conserved three transmembrane domains and a NPA motif. AQP ancestors probably started in prokaryotes by the duplication of half AQP genes to be diversified into CAQPs or AQGPs by evolving a subfamily-specific carboxyl-terminal NPA motif. Both AQP subfamilies may have been carried over to unicellular eukaryotic ancestors, protists and further to multicellular organisms. Although fungus lineage has kept both AQP subfamilies, the plant lineage has lost AQGP after algal ancestors with extensive diversifications of CAQPs into PIP, TIP, SIP, XIP, HIP and LIP with a possible horizontal transfer of NIP from bacteria. Interestingly, the animal lineage has obtained new SAQP subfamily with highly deviated NPA motifs, especially at the amino-terminal halves in both prostomial and deuterostomial animals. The prostomial lineage has lost AQGP after hymenoptera, while the deuterostomial lineage has kept all three subfamilies up to the vertebrate with diversified CAQPs (AQP0, 1, 2, 4, 5, 6, 8) and AQGPs (AQP3, 7, 9, 10) with limited SAQPs (AQP11, 12) in mammals. Whole-genome duplications, local gene duplications and horizontal gene transfers may have produced the AQP diversity with adaptive selections and functional alternations in response to environment changes. With the above evolutionary perspective in mind, the function of each AQP could be speculated by comparison among species to get new insights into physiological roles of AQPs . This evolutionary guidance in AQP research will lead to deeper understandings of water and solute homeostasis.}, } @article {pmid28253955, year = {2017}, author = {López-Otín, C and Mariño, G}, title = {Tagged ATG8-Coding Constructs for the In Vitro and In Vivo Assessment of ATG4 Activity.}, journal = {Methods in enzymology}, volume = {587}, number = {}, pages = {189-205}, doi = {10.1016/bs.mie.2016.11.001}, pmid = {28253955}, issn = {1557-7988}, mesh = {Animals ; Autophagy ; Autophagy-Related Protein 8 Family/*genetics/metabolism ; Autophagy-Related Proteins/genetics/metabolism ; Cells, Cultured ; Cysteine Endopeptidases/analysis/genetics/*metabolism ; Genetic Vectors ; Humans ; Mammals/genetics ; Mice ; Molecular Biology/*methods ; Recombinant Proteins/genetics/metabolism ; Transfection ; }, abstract = {Autophagy is a catabolic pathway, which mediates the degradation of cytoplasmic components and sustains many essential cellular functions. More than 30 genes have been involved in different aspects of this essential process in simple eukaryotes as yeast. Among these genes, those coding for members of the Atg4-Atg8 proteolytic system have acquired a high degree of complexity throughout evolution. Contrasting with the situation in unicellular eukaryotes, in which the system is composed by just a single protease (Atg4) and a single substrate (Atg8), evolution has led to the presence of several members for both Atg4 and Atg8 families in multicellular organisms. In human cells, there are four Atg4 proteases and six Atg8 substrates, which have probably evolved to cope with specific requirements for autophagic pathway in more complex scenarios. Despite these considerations, the reasons for the evolutionarily acquired complexity of this proteolytic system are still not completely understood. In this work, we describe two different applications of a relatively simple but useful technique to analyze protease-substrate specificity of this system in mammalian cells. By using the described technique, it is possible to determine the cellular efficiency in the initial cleavage for each of the Atg8 family members in diverse experimental settings both in cultured cells and live laboratory mice.}, } @article {pmid28250339, year = {2017}, author = {Cahill, MA}, title = {The evolutionary appearance of signaling motifs in PGRMC1.}, journal = {Bioscience trends}, volume = {11}, number = {2}, pages = {179-192}, doi = {10.5582/bst.2017.01009}, pmid = {28250339}, issn = {1881-7823}, mesh = {Animals ; Humans ; Membrane Proteins/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Signal Transduction/genetics/physiology ; }, abstract = {A complex PGRMC1-centred regulatory system controls multiple cell functions. Although PGRMC1 is phosphorylated at several positions, we do not understand the mechanisms regulating its function. PGRMC1 is the archetypal member of the membrane associated progesterone receptor (MAPR) family. Phylogentic comparison of MAPR proteins suggests that the ancestral metazoan "PGRMC-like" MAPR gene resembled PGRMC1/PGRMC2, containing the equivalents of PGRMC1 Y139 and Y180 SH2 target motifs. It later acquired a CK2 site with phosphoacceptor at S181. Separate PGRMC1 and PGRMC2 genes with this "PGRMC-like" structure diverged after the separation of vertebrates from protochordates. Terrestrial tetrapods possess a novel proline-rich PGRMC1 SH3 target motif centred on P64 which in mammals is augmented by a phosphoacceptor at PGRMC1 S54, and in primates by an additional S57 CK2 site. All of these phosphoacceptors are phosphorylated in vivo. This study suggests that an increasingly sophisticated system of PGRMC1-modulated multicellular functional regulation has characterised animal evolution since Precambrian times.}, } @article {pmid28247585, year = {2017}, author = {Frenk, S and Pizza, G and Walker, RV and Houseley, J}, title = {Aging yeast gain a competitive advantage on non-optimal carbon sources.}, journal = {Aging cell}, volume = {16}, number = {3}, pages = {602-604}, pmid = {28247585}, issn = {1474-9726}, support = {088335/WT_/Wellcome Trust/United Kingdom ; BBS/E/B/0000H247/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /MRC_/Medical Research Council/United Kingdom ; 088335/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Acetic Acid/metabolism/pharmacology ; Adaptation, Physiological/*genetics ; Carbon/*metabolism ; Cell Division ; Fermentation ; Galactose/metabolism/pharmacology ; Glucose/metabolism/pharmacology ; Metabolic Networks and Pathways/*genetics ; Raffinose/metabolism/pharmacology ; Saccharomyces cerevisiae/*drug effects/genetics/growth & development/*metabolism ; }, abstract = {Animals, plants and fungi undergo an aging process with remarkable physiological and molecular similarities, suggesting that aging has long been a fact of life for eukaryotes and one to which our unicellular ancestors were subject. Key biochemical pathways that impact longevity evolved prior to multicellularity, and the interactions between these pathways and the aging process therefore emerged in ancient single-celled eukaryotes. Nevertheless, we do not fully understand how aging impacts the fitness of unicellular organisms, and whether such cells gain a benefit from modulating rather than simply suppressing the aging process. We hypothesized that age-related loss of fitness in single-celled eukaryotes may be counterbalanced, partly or wholly, by a transition from a specialist to a generalist life-history strategy that enhances adaptability to other environments. We tested this hypothesis in budding yeast using competition assays and found that while young cells are more successful in glucose, highly aged cells outcompete young cells on other carbon sources such as galactose. This occurs because aged yeast divide faster than young cells in galactose, reversing the normal association between age and fitness. The impact of aging on single-celled organisms is therefore complex and may be regulated in ways that anticipate changing nutrient availability. We propose that pathways connecting nutrient availability with aging arose in unicellular eukaryotes to capitalize on age-linked diversity in growth strategy and that individual cells in higher eukaryotes may similarly diversify during aging to the detriment of the organism as a whole.}, } @article {pmid28242741, year = {2017}, author = {Cavalier-Smith, T}, title = {Correction to 'Origin of animal multicellularity: precursors, causes, consequences-the choanoflagellate/sponge transition, neurogenesis and the Cambrian explosion'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1718}, pages = {}, doi = {10.1098/rstb.2017.0001}, pmid = {28242741}, issn = {1471-2970}, } @article {pmid28241893, year = {2017}, author = {Zemková, M and Zahradník, D and Mokrejš, M and Flegr, J}, title = {Parasitism as the main factor shaping peptide vocabularies in current organisms.}, journal = {Parasitology}, volume = {144}, number = {7}, pages = {975-983}, doi = {10.1017/S0031182017000191}, pmid = {28241893}, issn = {1469-8161}, mesh = {Animals ; *Biological Evolution ; Helminth Proteins/*analysis ; *Host-Parasite Interactions ; Peptides/*analysis ; *Proteome ; Protozoan Proteins/*analysis ; }, abstract = {Self/non-self-discrimination by vertebrate immune systems is based on the recognition of the presence of peptides in proteins of a parasite that are not contained in the proteins of a host. Therefore, a reduction of the number of 'words' in its own peptide vocabulary could be an efficient evolutionary strategy of parasites for escaping recognition. Here, we compared peptide vocabularies of 30 endoparasitic and 17 free-living unicellular organisms and also eight multicellular parasitic and 16 multicellular free-living organisms. We found that both unicellular and multicellular parasites used a significantly lower number of different pentapeptides than free-living controls. Impoverished pentapeptide vocabularies in parasites were observed across all five clades that contain both the parasitic and free-living species. The effect of parasitism on a number of peptides used in an organism's proteins is larger than effects of all other studied factors, including the size of a proteome, the number of encoded proteins, etc. This decrease of pentapeptide diversity was partly compensated for by an increased number of hexapeptides. Our results support the hypothesis of parasitism-associated reduction of peptide vocabulary and suggest that T-cell receptors mostly recognize the five amino acids-long part of peptides that are presented in the groove of major histocompatibility complex molecules.}, } @article {pmid28230734, year = {2017}, author = {Cahoon, AB and Nauss, JA and Stanley, CD and Qureshi, A}, title = {Deep Transcriptome Sequencing of Two Green Algae, Chara vulgaris and Chlamydomonas reinhardtii, Provides No Evidence of Organellar RNA Editing.}, journal = {Genes}, volume = {8}, number = {2}, pages = {}, pmid = {28230734}, issn = {2073-4425}, abstract = {Nearly all land plants post-transcriptionally modify specific nucleotides within RNAs, a process known as RNA editing. This adaptation allows the correction of deleterious mutations within the asexually reproducing and presumably non-recombinant chloroplast and mitochondrial genomes. There are no reports of RNA editing in any of the green algae so this phenomenon is presumed to have originated in embryophytes either after the invasion of land or in the now extinct algal ancestor of all land plants. This was challenged when a recent in silico screen for RNA edit sites based on genomic sequence homology predicted edit sites in the green alga Chara vulgaris, a multicellular alga found within the Streptophyta clade and one of the closest extant algal relatives of land plants. In this study, the organelle transcriptomes of C. vulgaris and Chlamydomonas reinhardtii were deep sequenced for a comprehensive assessment of RNA editing. Initial analyses based solely on sequence comparisons suggested potential edit sites in both species, but subsequent high-resolution melt analysis, RNase H-dependent PCR (rhPCR), and Sanger sequencing of DNA and complementary DNAs (cDNAs) from each of the putative edit sites revealed them to be either single-nucleotide polymorphisms (SNPs) or spurious deep sequencing results. The lack of RNA editing in these two lineages is consistent with the current hypothesis that RNA editing evolved after embryophytes split from its ancestral algal lineage.}, } @article {pmid28222679, year = {2017}, author = {Skippington, E and Barkman, TJ and Rice, DW and Palmer, JD}, title = {Comparative mitogenomics indicates respiratory competence in parasitic Viscum despite loss of complex I and extreme sequence divergence, and reveals horizontal gene transfer and remarkable variation in genome size.}, journal = {BMC plant biology}, volume = {17}, number = {1}, pages = {49}, pmid = {28222679}, issn = {1471-2229}, mesh = {DNA, Plant ; Electron Transport Chain Complex Proteins/genetics ; Electron Transport Complex I/*genetics/metabolism ; *Evolution, Molecular ; Gene Deletion ; *Gene Transfer, Horizontal ; Genes, Plant ; *Genetic Variation ; Genome, Mitochondrial ; *Genome, Plant ; Molecular Sequence Annotation ; Plant Proteins/genetics ; RNA, Plant ; RNA, Ribosomal ; Sequence Analysis, DNA ; Species Specificity ; Viscum/*genetics/metabolism ; Viscum album/genetics/metabolism ; }, abstract = {BACKGROUND: Aerobically respiring eukaryotes usually contain four respiratory-chain complexes (complexes I-IV) and an ATP synthase (complex V). In several lineages of aerobic microbial eukaryotes, complex I has been lost, with an alternative, nuclear-encoded NADH dehydrogenase shown in certain cases to bypass complex I and oxidize NADH without proton translocation. The first loss of complex I in any multicellular eukaryote was recently reported in two studies; one sequenced the complete mitogenome of the hemiparasitic aerial mistletoe, Viscum scurruloideum, and the other sequenced the V. album mitogenome. The V. scurruloideum study reported no significant additional loss of mitochondrial genes or genetic function, but the V. album study postulated that mitochondrial genes encoding all ribosomal RNAs and proteins of all respiratory complexes are either absent or pseudogenes, thus raising questions as to whether the mitogenome and oxidative respiration are functional in this plant.

RESULTS: To determine whether these opposing conclusions about the two Viscum mitogenomes reflect a greater degree of reductive/degenerative evolution in V. album or instead result from interpretative and analytical differences, we reannotated and reanalyzed the V. album mitogenome and compared it with the V. scurruloideum mitogenome. We find that the two genomes share a complete complement of mitochondrial rRNA genes and a typical complement of genes encoding respiratory complexes II-V. Most Viscum mitochondrial protein genes exhibit very high levels of divergence yet are evolving under purifying, albeit relaxed selection. We discover two cases of horizontal gene transfer in V. album and show that the two Viscum mitogenomes differ by 8.6-fold in size (66 kb in V. scurruloideum; 565 kb in V. album).

CONCLUSIONS: Viscum mitogenomes are extraordinary compared to other plant mitogenomes in terms of their wide size range, high rates of synonymous substitutions, degree of relaxed selection, and unprecedented loss of respiratory complex I. However, contrary to the initial conclusions regarding V. album, both Viscum mitogenomes possess conventional sets of rRNA and, excepting complex I, respiratory genes. Both plants should therefore be able to carry out aerobic respiration. Moreover, with respect to size, the V. scurruloideum mitogenome has experienced a greater level of reductive evolution.}, } @article {pmid28217903, year = {2017}, author = {Arias Del Angel, JA and Escalante, AE and Martínez-Castilla, LP and Benítez, M}, title = {An Evo-Devo Perspective on Multicellular Development of Myxobacteria.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {328}, number = {1-2}, pages = {165-178}, doi = {10.1002/jez.b.22727}, pmid = {28217903}, issn = {1552-5015}, mesh = {*Biological Evolution ; *Developmental Biology ; Gene Expression Regulation, Bacterial/*physiology ; Myxococcales/*cytology/*genetics ; }, abstract = {The transition to multicellularity, recognized as one the major transitions in evolution, has occurred independently several times. While multicellular development has been extensively studied in zygotic organisms including plant and animal groups, just a few aggregative multicellular organisms have been employed as model organisms for the study of multicellularity. Studying different evolutionary origins and modes of multicellularity enables comparative analyses that can help identifying lineage-specific aspects of multicellular evolution and generic factors and mechanisms involved in the transition to multicellularity. Among aggregative multicellular organisms, myxobacteria are a valuable system to explore the particularities that aggregation confers to the evolution of multicellularity and mechanisms shared with clonal organisms. Moreover, myxobacteria species develop fruiting bodies displaying a range of morphological diversity. In this review, we aim to synthesize diverse lines of evidence regarding myxobacteria development and discuss them in the context of Evo-Devo concepts and approaches. First, we briefly describe the developmental processes in myxobacteria, present an updated comparative analysis of the genes involved in their developmental processes and discuss these and other lines of evidence in terms of co-option and developmental system drift, two concepts key to Evo-Devo studies. Next, as has been suggested from Evo-Devo approaches, we discuss how broad comparative studies and integration of diverse genetic, physicochemical, and environmental factors into experimental and theoretical models can further our understanding of myxobacterial development, phenotypic variation, and evolution.}, } @article {pmid28214944, year = {2017}, author = {Basile, A and Fambrini, M and Pugliesi, C}, title = {The vascular plants: open system of growth.}, journal = {Development genes and evolution}, volume = {227}, number = {2}, pages = {129-157}, pmid = {28214944}, issn = {1432-041X}, mesh = {*Evolution, Molecular ; Magnoliopsida/*genetics/growth & development/metabolism ; Meristem/*genetics/growth & development/metabolism ; Plant Growth Regulators/metabolism ; Plant Proteins/genetics/metabolism ; }, abstract = {What is fascinating in plants (true also in sessile animals such as corals and hydroids) is definitely their open and indeterminate growth, as a result of meristematic activity. Plants as well as animals are characterized by a multicellular organization, with which they share a common set of genes inherited from a common eukaryotic ancestor; nevertheless, circa 1.5 billion years of evolutionary history made the two kingdoms very different in their own developmental biology. Flowering plants, also known as angiosperms, arose during the Cretaceous Period (145-65 million years ago), and up to date, they count around 235,000 species, representing the largest and most diverse group within the plant kingdom. One of the foundations of their success relies on the plant-pollinator relationship, essentially unique to angiosperms that pushed large speciation in both plants and insects and on the presence of the carpel, the structure devoted to seed enclosure. A seed represents the main organ preserving the genetic information of a plant; during embryogenesis, the primary axis of development is established by two groups of pluripotent cells: the shoot apical meristem (SAM), responsible for gene rating all aboveground organs, and the root apical meristem (RAM), responsible for producing all underground organs. During postembryonic shoot development, axillary meristem (AM) initiation and outgrowth are responsible for producing all secondary axes of growth including inflorescence branches or flowers. The production of AMs is tightly linked to the production of leaves and their separation from SAM. As leaf primordia are formed on the flanks of the SAM, a region between the apex and the developing organ is established and referred to as boundary zone. Interaction between hormones and the gene network in the boundary zone is fundamental for AM initiation. AMs only develop at the adaxial base of the leaf; thus, AM initiation is also strictly associated with leaf polarity. AMs function as new SAMs: form axillary buds with a few leaves and then the buds can either stay dormant or develop into shoot branches to define a plant architecture, which in turn affects assimilate production and reproductive efficiency. Therefore, the radiation of angiosperms was accompanied by a huge diversification in growth forms that determine an enormous morphological plasticity helping plants to environmental changes. In this review, we focused on the developmental processes of AM initiation and outgrowth. In particular, we summarized the primary growth of SAM, the key role of positional signals for AM initiation, and the dissection of molecular players involved in AM initiation and outgrowth. Finally, the interaction between phytohormone signals and gene regulatory network controlling AM development was discussed.}, } @article {pmid28207760, year = {2017}, author = {Neeb, ZT and Hogan, DJ and Katzman, S and Zahler, AM}, title = {Preferential expression of scores of functionally and evolutionarily diverse DNA and RNA-binding proteins during Oxytricha trifallax macronuclear development.}, journal = {PloS one}, volume = {12}, number = {2}, pages = {e0170870}, pmid = {28207760}, issn = {1932-6203}, support = {T32 GM008646/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA, Protozoan/*genetics ; *Evolution, Molecular ; *Gene Expression Profiling ; Gene Expression Regulation ; High-Throughput Nucleotide Sequencing ; Macronucleus/genetics/*metabolism ; Oxytricha/genetics/growth & development/*metabolism ; Phylogeny ; Protozoan Proteins/genetics/*metabolism ; RNA-Binding Proteins/genetics/*metabolism ; }, abstract = {During its sexual reproduction, the stichotrichous ciliate Oxytricha trifallax orchestrates a remarkable transformation of one of the newly formed germline micronuclear genomes. Hundreds of thousands of gene pieces are stitched together, excised from chromosomes, and replicated dozens of times to yield a functional somatic macronuclear genome composed of ~16,000 distinct DNA molecules that typically encode a single gene. Little is known about the proteins that carry out this process. We profiled mRNA expression as a function of macronuclear development and identified hundreds of mRNAs preferentially expressed at specific times during the program. We find that a disproportionate number of these mRNAs encode proteins that are involved in DNA and RNA functions. Many mRNAs preferentially expressed during macronuclear development have paralogs that are either expressed constitutively or are expressed at different times during macronuclear development, including many components of the RNA polymerase II machinery and homologous recombination complexes. Hundreds of macronuclear development-specific genes encode proteins that are well-conserved among multicellular eukaryotes, including many with links to germline functions or development. Our work implicates dozens of DNA and RNA-binding proteins with diverse evolutionary trajectories in macronuclear development in O. trifallax. It suggests functional connections between the process of macronuclear development in unicellular ciliates and germline specialization and differentiation in multicellular organisms, and argues that gene duplication is a key source of evolutionary innovation in this process.}, } @article {pmid28204813, year = {2017}, author = {Agnati, LF and Marcoli, M and Leo, G and Maura, G and Guidolin, D}, title = {Homeostasis and the concept of 'interstitial fluids hierarchy': Relevance of cerebrospinal fluid sodium concentrations and brain temperature control (Review).}, journal = {International journal of molecular medicine}, volume = {39}, number = {3}, pages = {487-497}, pmid = {28204813}, issn = {1791-244X}, mesh = {Animals ; Biological Evolution ; Body Temperature Regulation ; Brain/*physiology ; Cerebrospinal Fluid/metabolism ; Extracellular Fluid/*metabolism ; Feedback, Physiological ; *Homeostasis ; Humans ; Kidney/physiology ; Sodium/metabolism ; }, abstract = {In this review, the aspects and further developments of the concept of homeostasis are discussed also in the perspective of their possible impact in the clinical practice, particularly as far as psychic homeostasis is concerned. A brief historical survey and comments on the concept of homeostasis and allostasis are presented to introduce our proposal that is based on the classical assumption of the interstitial fluid (ISF) as the internal medium for multicellular organisms. However, the new concept of a hierarchic role of ISF of the various organs is introduced. Additionally, it is suggested that particularly for some chemico‑physical parameters, oscillatory rhythms within their proper set‑ranges should be considered a fundamental component of homeostasis. Against this background, we propose that the brain ISF has the highest hierarchic role in human beings, providing the optimal environment, not simply for brain cell survival, but also for brain complex functions and the oscillatory rhythms of some parameters, such as cerebrospinal fluid sodium and brain ISF pressure waves, which may play a crucial role in brain physio‑pathological states. Thus, according to this proposal, the brain ISF represents the real internal medium since the maintenance of its dynamic intra-set-range homeostasis is the main factor for a free and independent life of higher vertebrates. Furthermore, the evolutionary links between brain and kidney and their synergistic role in H2O/Na balance and brain temperature control are discussed. Finally, it is surmised that these two interrelated parameters have deep effects on the Central Nervous System (CNS) higher integrative actions such those linked to psychic homeostasis.}, } @article {pmid28204529, year = {2016}, author = {Herrero, A and Stavans, J and Flores, E}, title = {The multicellular nature of filamentous heterocyst-forming cyanobacteria.}, journal = {FEMS microbiology reviews}, volume = {40}, number = {6}, pages = {831-854}, doi = {10.1093/femsre/fuw029}, pmid = {28204529}, issn = {1574-6976}, mesh = {Anabaena ; Cell Physiological Phenomena/*physiology ; *Cyanobacteria/cytology/physiology ; }, abstract = {Cyanobacteria carry out oxygenic photosynthesis, play a key role in the cycling of carbon and nitrogen in the biosphere, and have had a large impact on the evolution of life and the Earth itself. Many cyanobacterial strains exhibit a multicellular lifestyle, growing as filaments that can be hundreds of cells long and endowed with intercellular communication. Furthermore, under depletion of combined nitrogen, filament growth requires the activity of two interdependent cell types: vegetative cells that fix CO2 and heterocysts that fix N2. Intercellular molecular transfer is essential for signaling involved in the regulation of heterocyst differentiation and for reciprocal nutrition of heterocysts and vegetative cells. Here we review various aspects of multicellularity in cyanobacterial filaments and their differentiation, including filament architecture with emphasis on the structures used for intercellular communication; we survey theoretical models that have been put forward to understand heterocyst patterning and discuss the factors that need to be considered for these models to reflect the biological entity; and finally, since cell division in filamentous cyanobacteria has the peculiarity of producing linked instead of independent cells, we review distinct aspects of cell division in these organisms.}, } @article {pmid28194138, year = {2017}, author = {Rodríguez-Torres, MD and Islas-Robles, Á and Gómez-Lunar, Z and Delaye, L and Hernández-González, I and Souza, V and Travisano, M and Olmedo-Álvarez, G}, title = {Phenotypic Microdiversity and Phylogenetic Signal Analysis of Traits Related to Social Interaction in Bacillus spp. from Sediment Communities.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {29}, pmid = {28194138}, issn = {1664-302X}, abstract = {Understanding the relationship between phylogeny and predicted traits is important to uncover the dimension of the predictive power of a microbial composition approach. Numerous works have addressed the taxonomic composition of bacteria in communities, but little is known about trait heterogeneity in closely related bacteria that co-occur in communities. We evaluated a sample of 467 isolates from the Churince water system of the Cuatro Cienegas Basin (CCB), enriched for Bacillus spp. The 16S rRNA gene revealed a random distribution of taxonomic groups within this genus among 11 sampling sites. A subsample of 141 Bacillus spp. isolates from sediment, with seven well-represented species was chosen to evaluate the heterogeneity and the phylogenetic signal of phenotypic traits that are known to diverge within small clades, such as substrate utilization, and traits that are conserved deep in the lineage, such as prototrophy, swarming and biofilm formation. We were especially interested in evaluating social traits, such as swarming and biofilm formation, for which cooperation is needed to accomplish a multicellular behavior and for which there is little information from natural communities. The phylogenetic distribution of traits, evaluated by the Purvis and Fritz's D statistics approached a Brownian model of evolution. Analysis of the phylogenetic relatedness of the clusters of members sharing the trait using consenTRAIT algorithm, revealed more clustering and deeper phylogenetic signal for prototrophy, biofilm and swimming compared to the data obtained for substrate utilization. The explanation to the observed Brownian evolution of social traits could be either loss due to complete dispensability or to compensated trait loss due to the availability of public goods. Since many of the evaluated traits can be considered to be collective action traits, such as swarming, motility and biofilm formation, the observed microdiversity within taxonomic groups might be explained by distributed functions in structured communities.}, } @article {pmid28189637, year = {2017}, author = {Sieber, KB and Bromley, RE and Dunning Hotopp, JC}, title = {Lateral gene transfer between prokaryotes and eukaryotes.}, journal = {Experimental cell research}, volume = {358}, number = {2}, pages = {421-426}, pmid = {28189637}, issn = {1090-2422}, support = {DP2 OD007372/OD/NIH HHS/United States ; R01 CA206188/CA/NCI NIH HHS/United States ; T32 DK067872/DK/NIDDK NIH HHS/United States ; 1-R01-CA206188/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/genetics ; Eukaryota/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics/physiology ; Humans ; Mitochondria/metabolism ; Prokaryotic Cells/*cytology ; }, abstract = {Lateral gene transfer (LGT) is an all-encompassing term for the movement of DNA between diverse organisms. LGT is synonymous with horizontal gene transfer, and the terms are used interchangeably throughout the scientific literature. While LGT has been recognized within the bacteria domain of life for decades, inter-domain LGTs are being increasingly described. LGTs between bacteria and complex multicellular organisms are of interest because they challenge the long-held dogma that such transfers could only occur in closely-related, single-celled organisms. Scientists will continue to challenge our understanding of LGT as we sequence more, diverse organisms, as we sequence more endosymbiont-colonized arthropods, and as we continue to appreciate LGT events, both young and old.}, } @article {pmid28188480, year = {2017}, author = {Sekimoto, H}, title = {Sexual reproduction and sex determination in green algae.}, journal = {Journal of plant research}, volume = {130}, number = {3}, pages = {423-431}, pmid = {28188480}, issn = {1618-0860}, mesh = {Biological Evolution ; Cell Adhesion/physiology ; Cell Fusion ; Chlamydomonas reinhardtii/genetics/growth & development ; Chlorophyta/*genetics/growth & development/*physiology ; Closterium/genetics/growth & development ; Fresh Water ; Life Cycle Stages/genetics/physiology ; Membrane Fusion/physiology ; Reproduction/*genetics/*physiology ; Sex Determination Processes/*genetics/*physiology ; Volvox/genetics/growth & development ; }, abstract = {The sexual reproductive processes of some representative freshwater green algae are reviewed. Chlamydomonas reinhardtii is a unicellular volvocine alga having two mating types: mating type plus (mt[+]) and mating type minus (mt[-]), which are controlled by a single, complex mating-type locus. Sexual adhesion between the gametes is mediated by sex-specific agglutinin molecules on their flagellar membranes. Cell fusion is initiated by an adhesive interaction between the mt[+] and mt[-] mating structures, followed by localized membrane fusion. The loci of sex-limited genes and the conformation of sex-determining regions have been rearranged during the evolution of volvocine algae; however, the essential function of the sex-determining genes of the isogamous unicellular Chlamydomonas reinhardtii is conserved in the multicellular oogamous Volvox carteri. The sexual reproduction of the unicellular charophycean alga, Closterium peracerosum-strigosum-littorale complex, is also focused on here. The sexual reproductive processes of heterothallic strains are controlled by two multifunctional sex pheromones, PR-IP and PR-IP Inducer, which independently promote multiple steps in conjugation at the appropriate times through different induction mechanisms. The molecules involved in sexual reproduction and sex determination have also been characterized.}, } @article {pmid28188197, year = {2017}, author = {Drumm, BT and Baker, SA}, title = {Teaching a changing paradigm in physiology: a historical perspective on gut interstitial cells.}, journal = {Advances in physiology education}, volume = {41}, number = {1}, pages = {100-109}, doi = {10.1152/advan.00154.2016}, pmid = {28188197}, issn = {1522-1229}, mesh = {Animals ; Gastrointestinal Motility/*physiology ; Gastrointestinal Tract/*cytology/*physiology ; Humans ; Muscle, Smooth/cytology/physiology ; Physiology/*education ; Teaching/*trends ; }, abstract = {The study and teaching of gastrointestinal (GI) physiology necessitates an understanding of the cellular basis of contractile and electrical coupling behaviors in the muscle layers that comprise the gut wall. Our knowledge of the cellular origin of GI motility has drastically changed over the last 100 yr. While the pacing and coordination of GI contraction was once thought to be solely attributable to smooth muscle cells, it is now widely accepted that the motility patterns observed in the GI tract exist as a result of a multicellular system, consisting of not only smooth muscle cells but also enteric neurons and distinct populations of specialized interstitial cells that all work in concert to ensure proper GI functions. In this historical perspective, we focus on the emerging role of interstitial cells in GI motility and examine the key discoveries and experiments that led to a major shift in a paradigm of GI physiology regarding the role of interstitial cells in modulating GI contractile patterns. A review of these now classic experiments and papers will enable students and educators to fully appreciate the complex, multicellular nature of GI muscles as well as impart lessons on how shifting paradigms in physiology are fueled by new technologies that lead to new emerging discoveries.}, } @article {pmid28179656, year = {2017}, author = {Hotamisligil, GS}, title = {Inflammation, metaflammation and immunometabolic disorders.}, journal = {Nature}, volume = {542}, number = {7640}, pages = {177-185}, pmid = {28179656}, issn = {1476-4687}, support = {R01 DK052539/DK/NIDDK NIH HHS/United States ; R01 HL125753/HL/NHLBI NIH HHS/United States ; R01 AI116901/AI/NIAID NIH HHS/United States ; }, mesh = {Adaptive Immunity/genetics ; Animals ; Clinical Trials as Topic ; Cytokines/metabolism ; Evolution, Molecular ; Genome-Wide Association Study ; Hormones/metabolism ; Humans ; Inflammation/complications/genetics/*immunology/*metabolism ; Invertebrates/immunology/metabolism ; Metabolic Diseases/complications/genetics/*immunology/*metabolism ; Obesity/complications/genetics/immunology/metabolism ; Organelles/metabolism ; Signal Transduction ; }, abstract = {Proper regulation and management of energy, substrate diversity and quantity, as well as macromolecular synthesis and breakdown processes, are fundamental to cellular and organismal survival and are paramount to health. Cellular and multicellular organization are defended by the immune response, a robust and critical system through which self is distinguished from non-self, pathogenic signals are recognized and eliminated, and tissue homeostasis is safeguarded. Many layers of evolutionarily conserved interactions occur between immune response and metabolism. Proper maintenance of this delicate balance is crucial for health and has important implications for many pathological states such as obesity, diabetes, and other chronic non-communicable diseases.}, } @article {pmid28176784, year = {2017}, author = {Nguyen, TA and Cissé, OH and Yun Wong, J and Zheng, P and Hewitt, D and Nowrousian, M and Stajich, JE and Jedd, G}, title = {Innovation and constraint leading to complex multicellularity in the Ascomycota.}, journal = {Nature communications}, volume = {8}, number = {}, pages = {14444}, pmid = {28176784}, issn = {2041-1723}, support = {P01 GM068087/GM/NIGMS NIH HHS/United States ; }, mesh = {Ascomycota/*cytology/genetics ; Biodiversity ; Biological Transport/physiology ; Computational Biology ; DNA, Fungal/*genetics ; Evolution, Molecular ; Fungal Proteins/*physiology ; Genome, Fungal/*physiology ; Phylogeny ; Sequence Alignment ; Whole Genome Sequencing ; }, abstract = {The advent of complex multicellularity (CM) was a pivotal event in the evolution of animals, plants and fungi. In the fungal Ascomycota, CM is based on hyphal filaments and arose in the Pezizomycotina. The genus Neolecta defines an enigma: phylogenetically placed in a related group containing mostly yeasts, Neolecta nevertheless possesses Pezizomycotina-like CM. Here we sequence the Neolecta irregularis genome and identify CM-associated functions by searching for genes conserved in Neolecta and the Pezizomycotina, which are absent or divergent in budding or fission yeasts. This group of 1,050 genes is enriched for functions related to diverse endomembrane systems and their organization. Remarkably, most show evidence for divergence in both yeasts. Using functional genomics, we identify new genes involved in fungal complexification. Together, these data show that rudimentary multicellularity is deeply rooted in the Ascomycota. Extensive parallel gene divergence during simplification and constraint leading to CM suggest a deterministic process where shared modes of cellular organization select for similarly configured organelle- and transport-related machineries.}, } @article {pmid28174248, year = {2017}, author = {Jones, VA and Dolan, L}, title = {MpWIP regulates air pore complex development in the liverwort Marchantia polymorpha.}, journal = {Development (Cambridge, England)}, volume = {144}, number = {8}, pages = {1472-1476}, pmid = {28174248}, issn = {1477-9129}, mesh = {Marchantia/anatomy & histology/*embryology/*metabolism/ultrastructure ; Mutation/genetics ; Plant Epidermis/cytology/*embryology/ultrastructure ; Plant Proteins/genetics/*metabolism ; Promoter Regions, Genetic/genetics ; Repressor Proteins/metabolism ; Transcription, Genetic ; }, abstract = {The colonisation of the land by plants was accompanied by the evolution of complex tissues and multicellular structures comprising different cell types as morphological adaptations to the terrestrial environment. Here, we show that the single WIP protein in the early-diverging land plant Marchantia polymorpha L. is required for the development of the multicellular gas exchange structure: the air pore complex. This 16-cell barrel-shaped structure surrounds an opening between epidermal cells that facilitates the exchange of gases between the chamber containing the photosynthetic cells inside the plant and the air outside. MpWIP is expressed in cells of the developing air pore complex and the morphogenesis of the complex is defective in plants with reduced MpWIP function. The role of WIP proteins in the control of different multicellular structures in M. polymorpha and the flowering plant Arabidopsis thaliana suggests that these proteins controlled the development of multicellular structures in the common ancestor of land plants. We hypothesise that WIP genes were subsequently co-opted in the control of morphogenesis of novel multicellular structures that evolved during the diversification of land plants.}, } @article {pmid28173090, year = {2017}, author = {Gallagher, MD and Macqueen, DJ}, title = {Evolution and Expression of Tissue Globins in Ray-Finned Fishes.}, journal = {Genome biology and evolution}, volume = {9}, number = {1}, pages = {32-47}, pmid = {28173090}, issn = {1759-6653}, support = {BB/J01446X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Biological Evolution ; *Evolution, Molecular ; Fish Proteins/*genetics ; Fishes/*classification/*genetics ; Globins/*genetics ; Phylogeny ; }, abstract = {The globin gene family encodes oxygen-binding hemeproteins conserved across the major branches of multicellular life. The origins and evolutionary histories of complete globin repertoires have been established for many vertebrates, but there remain major knowledge gaps for ray-finned fish. Therefore, we used phylogenetic, comparative genomic and gene expression analyses to discover and characterize canonical “non-blood” globin family members (i.e., myoglobin, cytoglobin, neuroglobin, globin-X, and globin-Y) across multiple ray-finned fish lineages, revealing novel gene duplicates (paralogs) conserved from whole genome duplication (WGD) and small-scale duplication events. Our key findings were that: (1) globin-X paralogs in teleosts have been retained from the teleost-specific WGD, (2) functional paralogs of cytoglobin, neuroglobin, and globin-X, but not myoglobin, have been conserved from the salmonid-specific WGD, (3) triplicate lineage-specific myoglobin paralogs are conserved in arowanas (Osteoglossiformes), which arose by tandem duplication and diverged under positive selection, (4) globin-Y is retained in multiple early branching fish lineages that diverged before teleosts, and (5) marked variation in tissue-specific expression of globin gene repertoires exists across ray-finned fish evolution, including several previously uncharacterized sites of expression. In this respect, our data provide an interesting link between myoglobin expression and the evolution of air breathing in teleosts. Together, our findings demonstrate great-unrecognized diversity in the repertoire and expression of nonblood globins that has arisen during ray-finned fish evolution.}, } @article {pmid28168289, year = {2017}, author = {Paulet, D and David, A and Rivals, E}, title = {Ribo-seq enlightens codon usage bias.}, journal = {DNA research : an international journal for rapid publication of reports on genes and genomes}, volume = {24}, number = {3}, pages = {303-210}, pmid = {28168289}, issn = {1756-1663}, mesh = {Animals ; Codon/analysis/*genetics ; Eukaryota/genetics ; Evolution, Molecular ; Genomics/*methods ; High-Throughput Nucleotide Sequencing ; Humans ; *Protein Biosynthesis ; RNA, Messenger ; Ribosomes ; Sequence Analysis, RNA ; *Transcriptome ; }, abstract = {Codon usage is biased between lowly and highly expressed genes in a genome-specific manner. This universal bias has been well assessed in some unicellular species, but remains problematic to assess in more complex species. We propose a new method to compute codon usage bias based on genome wide translational data. A new technique based on sequencing of ribosome protected mRNA fragments (Ribo-seq) allowed us to rank genes and compute codon usage bias with high precision for a great variety of species, including mammals. Genes ranking using Ribo-Seq data confirms the influence of the tRNA pool on codon usage bias and shows a decreasing bias in multicellular species. Ribo-Seq analysis also makes possible to detect preferred codons without information on genes function.}, } @article {pmid28161621, year = {2017}, author = {Tollis, M and Schiffman, JD and Boddy, AM}, title = {Evolution of cancer suppression as revealed by mammalian comparative genomics.}, journal = {Current opinion in genetics & development}, volume = {42}, number = {}, pages = {40-47}, doi = {10.1016/j.gde.2016.12.004}, pmid = {28161621}, issn = {1879-0380}, mesh = {Animals ; Carcinogenesis/*genetics ; Conserved Sequence/genetics ; DNA Damage/genetics ; DNA Repair/genetics ; *Evolution, Molecular ; *Genomics ; Humans ; Mammals ; Neoplasms/*genetics/pathology ; }, abstract = {Cancer suppression is an important feature in the evolution of large and long-lived animals. While some tumor suppression pathways are conserved among all multicellular organisms, others mechanisms of cancer resistance are uniquely lineage specific. Comparative genomics has become a powerful tool to discover these unique and shared molecular adaptations in respect to cancer suppression. These findings may one day be translated to human patients through evolutionary medicine. Here, we will review theory and methods of comparative cancer genomics and highlight major findings of cancer suppression across mammals. Our current knowledge of cancer genomics suggests that more efficient DNA repair and higher sensitivity to DNA damage may be the key to tumor suppression in large or long-lived mammals.}, } @article {pmid28158973, year = {2017}, author = {Mohanta, TK and Kumar, P and Bae, H}, title = {Genomics and evolutionary aspect of calcium signaling event in calmodulin and calmodulin-like proteins in plants.}, journal = {BMC plant biology}, volume = {17}, number = {1}, pages = {38}, pmid = {28158973}, issn = {1471-2229}, mesh = {Amino Acid Sequence ; *Biological Evolution ; Calcium/metabolism ; *Calcium Signaling ; Calmodulin/chemistry/*genetics/metabolism ; Genomics ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; Plants/chemistry/classification/*genetics/metabolism ; Sequence Alignment ; }, abstract = {BACKGROUND: Ca[2+] ion is a versatile second messenger that operate in a wide ranges of cellular processes that impact nearly every aspect of life. Ca[2+] regulates gene expression and biotic and abiotic stress responses in organisms ranging from unicellular algae to multi-cellular higher plants through the cascades of calcium signaling processes.

RESULTS: In this study, we deciphered the genomics and evolutionary aspects of calcium signaling event of calmodulin (CaM) and calmodulin like- (CML) proteins. We studied the CaM and CML gene family of 41 different species across the plant lineages. Genomic analysis showed that plant encodes more calmodulin like-protein than calmodulins. Further analyses showed, the majority of CMLs were intronless, while CaMs were intron rich. Multiple sequence alignment showed, the EF-hand domain of CaM contains four conserved D-x-D motifs, one in each EF-hand while CMLs contain only one D-x-D-x-D motif in the fourth EF-hand. Phylogenetic analysis revealed that, the CMLs were evolved earlier than CaM and later diversified. Gene expression analysis demonstrated that different CaM and CMLs genes were express differentially in different tissues in a spatio-temporal manner.

CONCLUSION: In this study we provided in detailed genome-wide identifications and characterization of CaM and CML protein family, phylogenetic relationships, and domain structure. Expression study of CaM and CML genes were conducted in Glycine max and Phaseolus vulgaris. Our study provides a strong foundation for future functional research in CaM and CML gene family in plant kingdom.}, } @article {pmid28148211, year = {2017}, author = {Buonanno, F and Anesi, A and Giuseppe, GD and Guella, G and Ortenzi, C}, title = {Chemical Defense by Erythrolactones in the Euryhaline Ciliated Protist, Pseudokeronopsis erythrina.}, journal = {Zoological science}, volume = {34}, number = {1}, pages = {42-51}, doi = {10.2108/zs160123}, pmid = {28148211}, issn = {0289-0003}, mesh = {Animals ; Ciliophora/genetics/*metabolism ; Invertebrates ; Lactones/*chemistry/metabolism/*toxicity ; Molecular Structure ; Phylogeny ; Predatory Behavior ; }, abstract = {Pseudokeronopsis erythrina produces three new secondary metabolites, erythrolactones A2, B2 and C2, and their respective sulfate esters (A1, B1, C1), the structures of which have been recently elucidated on the basis of NMR spectroscopic data coupled to high resolution mass measurements (HR-MALDI-TOF). An analysis of the discharge of the protozoan pigment granules revealed that the non-sulfonated erythrolactones are exclusively stored in these cortical organelles, which are commonly used by a number of ciliates as chemical weapons in offense/defense interactions with prey and predators. We evaluated the toxic activity of pigment granule discharge on a panel of free-living ciliates and micro-invertebrates, and the activity of each single purified erythrolactone on three ciliate species. We also observed predator-prey interactions of P. erythrina with unicellular and multicellular predators. Experimental results confirm that only P. erythrina cells with discharged pigment granules were preferentially or exclusively hunted and eaten by at least some of its predators, whereas almost all intact (fully pigmented) cells remained alive. Our results indicate that erythrolactones are very effective as a chemical defense in P. erythrina.}, } @article {pmid28142193, year = {2017}, author = {Moormeier, DE and Bayles, KW}, title = {Staphylococcus aureus biofilm: a complex developmental organism.}, journal = {Molecular microbiology}, volume = {104}, number = {3}, pages = {365-376}, pmid = {28142193}, issn = {1365-2958}, support = {P01 AI083211/AI/NIAID NIH HHS/United States ; R01 AI038901/AI/NIAID NIH HHS/United States ; R01 AI125589/AI/NIAID NIH HHS/United States ; }, mesh = {Biofilms/*growth & development ; Staphylococcus aureus/*physiology ; }, abstract = {Chronic biofilm-associated infections caused by Staphylococcus aureus often lead to significant increases in morbidity and mortality, particularly when associated with indwelling medical devices. This has triggered a great deal of research attempting to understand the molecular mechanisms that control S. aureus biofilm formation and the basis for the recalcitrance of these multicellular structures to antibiotic therapy. The purpose of this review is to summarize our current understanding of S. aureus biofilm development, focusing on the description of a newly-defined, five-stage model of biofilm development and the mechanisms required for each stage. Importantly, this model includes an alternate view of the processes involved in microcolony formation in S. aureus and suggests that these structures originate as a result of stochastically regulated metabolic heterogeneity and proliferation within a maturing biofilm population, rather than a subtractive process involving the release of cell clusters from a thick, unstructured biofilm. Importantly, it is proposed that this new model of biofilm development involves the genetically programmed generation of metabolically distinct subpopulations of cells, resulting in an overall population that is better able to adapt to rapidly changing environmental conditions.}, } @article {pmid28131316, year = {2017}, author = {Tompitak, M and Vaillant, C and Schiessel, H}, title = {Genomes of Multicellular Organisms Have Evolved to Attract Nucleosomes to Promoter Regions.}, journal = {Biophysical journal}, volume = {112}, number = {3}, pages = {505-511}, pmid = {28131316}, issn = {1542-0086}, mesh = {Animals ; Base Sequence ; DNA/genetics/metabolism ; *Evolution, Molecular ; Genome, Human/*genetics ; Humans ; Nucleosomes/genetics/*metabolism ; *Promoter Regions, Genetic ; Saccharomyces cerevisiae/genetics ; }, abstract = {Sequences that influence nucleosome positioning in promoter regions, and their relation to gene regulation, have been the topic of much research over the last decade. In yeast, significant nucleosome-depleted regions are found, which facilitate transcription. With the arrival of nucleosome positioning maps for the human genome, it was discovered that in our genome, unlike in that of yeast, promoters encode for high nucleosome occupancy. In this work, we look at the genomes of a range of different organisms, to provide a catalog of nucleosome positioning signals in promoters across the tree of life. We utilize a computational model of the nucleosome, based on crystallographic analyses of the structure and elasticity of the nucleosome, to predict the nucleosome positioning signals in promoter regions. To be able to apply our model to large genomic datasets, we introduce an approximative scheme that makes use of the limited range of correlations in nucleosomal sequence preferences to create a computationally efficient approximation of the full biophysical model. Our predictions show that a clear distinction between unicellular and multicellular life is visible in the intrinsically encoded nucleosome affinity. Furthermore, the strength of the nucleosome positioning signals correlates with the complexity of the organism. We conclude that encoding for high nucleosome occupancy, as in the human genome, is in fact a universal feature of multicellular life.}, } @article {pmid28126046, year = {2017}, author = {Gaisin, VA and Kalashnikov, AM and Grouzdev, DS and Sukhacheva, MV and Kuznetsov, BB and Gorlenko, VM}, title = {Chloroflexus islandicus sp. nov., a thermophilic filamentous anoxygenic phototrophic bacterium from a geyser.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {67}, number = {5}, pages = {1381-1386}, doi = {10.1099/ijsem.0.001820}, pmid = {28126046}, issn = {1466-5034}, mesh = {Bacterial Proteins/chemistry ; Bacterial Typing Techniques ; Bacteriochlorophylls/chemistry ; Base Composition ; Carotenoids/chemistry ; Chloroflexus/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Iceland ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Water Microbiology ; }, abstract = {A novel, thermophilic filamentous anoxygenic phototrophic bacterium, strain isl-2T, was isolated from the Strokkur Geyser, Iceland. Strain isl-2T formed unbranched multicellular filaments with gliding motility. The cells formed no spores and stained Gram-negative. The existence of pili was described in a species of the genus Chloroflexus for the first time, to our knowledge. Optimal growth occurred at a pH range of 7.5-7.7 and at a temperature of 55 °C. Strain isl-2T grew photoheterotrophically under anaerobic conditions in the light and chemoheterotrophically under aerobic conditions in the dark. The major cellular fatty acids were C18 : 1ω9, C16 : 0, C18 : 0 and C18 : 0-OH. The major quinone was menaquinone-10. The photosynthetic pigments were bacteriochlorophylls c and a as well as β- and γ-carotenes. The results of phylogenetic analysis of the 16S rRNA gene sequences placed strain isl-2T into the genus Chloroflexus of the phylum Chloroflexi with Chloroflexus aggregans DSM 9485T as the closest relative (97.0 % identity). The whole-genome sequence of isl-2T was determined. Average nucleotide identity values obtained for isl-2T in comparison to available genomic sequences of other strains of members of the genus Chloroflexus were 81.4 % or less and digital DNA-DNA hybridisation values 22.8 % or less. The results of additional phylogenetic analysis of the PufLM and BchG amino acid sequences supported the separate position of the isl-2T phylotype from the phylotypes of other members of the genus Chloroflexus. On the basis of physiological and phylogenetic data as well as genomic data, it was suggested that isl-2T represents a novel species within the genus Chloroflexus, with the proposed name Chloroflexus islandicus sp. nov. The type strain of the species is isl-2T (=VKM B-2978T,=DSM 29225T,=JCM 30533T).}, } @article {pmid28116828, year = {2017}, author = {Arenas-Mena, C}, title = {The origins of developmental gene regulation.}, journal = {Evolution & development}, volume = {19}, number = {2}, pages = {96-107}, doi = {10.1111/ede.12217}, pmid = {28116828}, issn = {1525-142X}, mesh = {Animals ; *Biological Evolution ; Enhancer Elements, Genetic ; Eukaryota/cytology/genetics ; *Gene Expression Regulation, Developmental ; Prokaryotic Cells/metabolism ; Promoter Regions, Genetic ; }, abstract = {The leap from simple unicellularity to complex multicellularity remains one of life's major enigmas. The origins of metazoan developmental gene regulatory mechanisms are sought by analyzing gene regulation in extant eumetazoans, sponges, and unicellular organisms. The main hypothesis of this manuscript is that, developmental enhancers evolved from unicellular inducible promoters that diversified the expression of regulatory genes during metazoan evolution. Promoters and enhancers are functionally similar; both can regulate the transcription of distal promoters and both direct local transcription. Additionally, enhancers have experimentally characterized structural features that reveal their origin from inducible promoters. The distal co-operative regulation among promoters identified in unicellular opisthokonts possibly represents the precursor of distal regulation of promoters by enhancers. During metazoan evolution, constitutive-type promoters of regulatory genes would have acquired novel receptivity to distal regulatory inputs from promoters of inducible genes that eventually specialized as enhancers. The novel regulatory interactions would have caused constitutively expressed genes controlling differential gene expression in unicellular organisms to become themselves differentially expressed. The consequence of the novel regulatory interactions was that regulatory pathways of unicellular organisms became interlaced and ultimately evolved into the intricate developmental gene regulatory networks (GRNs) of extant metazoans.}, } @article {pmid28115992, year = {2017}, author = {Navratilova, P and Danks, GB and Long, A and Butcher, S and Manak, JR and Thompson, EM}, title = {Sex-specific chromatin landscapes in an ultra-compact chordate genome.}, journal = {Epigenetics & chromatin}, volume = {10}, number = {}, pages = {3}, pmid = {28115992}, issn = {1756-8935}, mesh = {Animals ; Chromatin/genetics/*metabolism ; Chromatin Immunoprecipitation ; DNA Methylation ; DNA Transposable Elements/genetics ; Female ; *Genome ; Histones/chemistry/genetics/metabolism ; Male ; Ovary/metabolism ; Promoter Regions, Genetic ; Protein Processing, Post-Translational ; RNA Polymerase II/genetics/metabolism ; Testis/metabolism ; Urochordata/*genetics ; }, abstract = {BACKGROUND: In multicellular organisms, epigenome dynamics are associated with transitions in the cell cycle, development, germline specification, gametogenesis and inheritance. Evolutionarily, regulatory space has increased in complex metazoans to accommodate these functions. In tunicates, the sister lineage to vertebrates, we examine epigenome adaptations to strong secondary genome compaction, sex chromosome evolution and cell cycle modes.

RESULTS: Across the 70 MB Oikopleura dioica genome, we profiled 19 histone modifications, and RNA polymerase II, CTCF and p300 occupancies, to define chromatin states within two homogeneous tissues with distinct cell cycle modes: ovarian endocycling nurse nuclei and mitotically proliferating germ nuclei in testes. Nurse nuclei had active chromatin states similar to other metazoan epigenomes, with large domains of operon-associated transcription, a general lack of heterochromatin, and a possible role of Polycomb PRC2 in dosage compensation. Testis chromatin states reflected transcriptional activity linked to spermatogenesis and epigenetic marks that have been associated with establishment of transgenerational inheritance in other organisms. We also uncovered an unusual chromatin state specific to the Y-chromosome, which combined active and heterochromatic histone modifications on specific transposable elements classes, perhaps involved in regulating their activity.

CONCLUSIONS: Compacted regulatory space in this tunicate genome is accompanied by reduced heterochromatin and chromatin state domain widths. Enhancers, promoters and protein-coding genes have conserved epigenomic features, with adaptations to the organization of a proportion of genes in operon units. We further identified features specific to sex chromosomes, cell cycle modes, germline identity and dosage compensation, and unusual combinations of histone PTMs with opposing consensus functions.}, } @article {pmid28112403, year = {2018}, author = {Torday, JS and Miller, WB}, title = {A systems approach to physiologic evolution: From micelles to consciousness.}, journal = {Journal of cellular physiology}, volume = {233}, number = {1}, pages = {162-167}, doi = {10.1002/jcp.25820}, pmid = {28112403}, issn = {1097-4652}, mesh = {Adaptation, Physiological ; Animals ; *Biological Evolution ; Body Temperature Regulation ; Homeostasis ; Humans ; Lung/physiology ; Physiology/*methods ; Pulmonary Ventilation ; *Systems Biology ; *Systems Integration ; Time Factors ; }, abstract = {A systems approach to evolutionary biology offers the promise of an improved understanding of the fundamental principles of life through the effective integration of many biologic disciplines. It is presented that any critical integrative approach to evolutionary development involves a paradigmatic shift in perspective, more than just the engagement of a large number of disciplines. Critical to this differing viewpoint is the recognition that all biological processes originate from the unicellular state and remain permanently anchored to that phase throughout evolutionary development despite their macroscopic appearances. Multicellular eukaryotic development can, therefore, be viewed as a series of connected responses to epiphenomena that proceeds from that base in continuous iterative maintenance of collective cellular homeostatic equipoise juxtaposed against an ever-changing and challenging environment. By following this trajectory of multicellular eukaryotic evolution from within unicellular First Principles of Physiology forward, the mechanistic nature of complex physiology can be identified through a step-wise analysis of a continuous arc of vertebrate evolution based upon serial exaptations.}, } @article {pmid28106309, year = {2017}, author = {Wang, D and Qu, Z and Yang, L and Zhang, Q and Liu, ZH and Do, T and Adelson, DL and Wang, ZY and Searle, I and Zhu, JK}, title = {Transposable elements (TEs) contribute to stress-related long intergenic noncoding RNAs in plants.}, journal = {The Plant journal : for cell and molecular biology}, volume = {90}, number = {1}, pages = {133-146}, pmid = {28106309}, issn = {1365-313X}, support = {R01 GM059138/GM/NIGMS NIH HHS/United States ; R01 GM070795/GM/NIGMS NIH HHS/United States ; }, mesh = {Abscisic Acid/pharmacology ; Arabidopsis/drug effects/genetics ; Cold Temperature ; DNA Transposable Elements/*genetics ; Gene Expression Profiling ; Gene Expression Regulation, Plant/drug effects/genetics ; Oryza/drug effects/genetics ; RNA, Long Noncoding/*genetics ; RNA, Plant/*genetics ; Sodium Chloride/pharmacology ; Zea mays/drug effects/genetics ; }, abstract = {Noncoding RNAs have been extensively described in plant and animal transcriptomes by using high-throughput sequencing technology. Of these noncoding RNAs, a growing number of long intergenic noncoding RNAs (lincRNAs) have been described in multicellular organisms, however the origins and functions of many lincRNAs remain to be explored. In many eukaryotic genomes, transposable elements (TEs) are widely distributed and often account for large fractions of plant and animal genomes yet the contribution of TEs to lincRNAs is largely unknown. By using strand-specific RNA-sequencing, we profiled the expression patterns of lincRNAs in Arabidopsis, rice and maize, and identified 47 611 and 398 TE-associated lincRNAs (TE-lincRNAs), respectively. TE-lincRNAs were more often derived from retrotransposons than DNA transposons and as retrotransposon copy number in both rice and maize genomes so did TE-lincRNAs. We validated the expression of these TE-lincRNAs by strand-specific RT-PCR and also demonstrated tissue-specific transcription and stress-induced TE-lincRNAs either after salt, abscisic acid (ABA) or cold treatments. For Arabidopsis TE-lincRNA11195, mutants had reduced sensitivity to ABA as demonstrated by longer roots and higher shoot biomass when compared to wild-type. Finally, by altering the chromatin state in the Arabidopsis chromatin remodelling mutant ddm1, unique lincRNAs including TE-lincRNAs were generated from the preceding untranscribed regions and interestingly inherited in a wild-type background in subsequent generations. Our findings not only demonstrate that TE-associated lincRNAs play important roles in plant abiotic stress responses but lincRNAs and TE-lincRNAs might act as an adaptive reservoir in eukaryotes.}, } @article {pmid28102347, year = {2017}, author = {Fernández, L and González, S and Campelo, AB and Martínez, B and Rodríguez, A and García, P}, title = {Low-level predation by lytic phage phiIPLA-RODI promotes biofilm formation and triggers the stringent response in Staphylococcus aureus.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {40965}, pmid = {28102347}, issn = {2045-2322}, mesh = {*Bacteriolysis ; Biofilms/*growth & development ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Host-Parasite Interactions ; Sequence Analysis, RNA ; Staphylococcus Phages/*growth & development ; Staphylococcus aureus/*physiology/*virology ; *Stress, Physiological ; }, abstract = {An important lesson from the war on pathogenic bacteria has been the need to understand the physiological responses and evolution of natural microbial communities. Bacterial populations in the environment are generally forming biofilms subject to some level of phage predation. These multicellular communities are notoriously resistant to antimicrobials and, consequently, very difficult to eradicate. This has sparked the search for new therapeutic alternatives, including phage therapy. This study demonstrates that S. aureus biofilms formed in the presence of a non-lethal dose of phage phiIPLA-RODI exhibit a unique physiological state that could potentially benefit both the host and the predator. Thus, biofilms formed under phage pressure are thicker and have a greater DNA content. Also, the virus-infected biofilm displayed major transcriptional differences compared to an untreated control. Significantly, RNA-seq data revealed activation of the stringent response, which could slow down the advance of the bacteriophage within the biofilm. The end result would be an equilibrium that would help bacterial cells to withstand environmental challenges, while maintaining a reservoir of sensitive bacterial cells available to the phage upon reactivation of the dormant carrier population.}, } @article {pmid28096354, year = {2017}, author = {Xing, S and Mehlhorn, DG and Wallmeroth, N and Asseck, LY and Kar, R and Voss, A and Denninger, P and Schmidt, VA and Schwarzländer, M and Stierhof, YD and Grossmann, G and Grefen, C}, title = {Loss of GET pathway orthologs in Arabidopsis thaliana causes root hair growth defects and affects SNARE abundance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {8}, pages = {E1544-E1553}, pmid = {28096354}, issn = {1091-6490}, mesh = {Adenosine Triphosphatases/metabolism ; Animals ; Arabidopsis/*physiology ; Arabidopsis Proteins/*metabolism ; Cell Membrane/*metabolism ; Cytosol/metabolism ; Endoplasmic Reticulum/metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; Homeostasis/physiology ; Mammals/physiology ; Membrane Fusion/physiology ; Molecular Chaperones/metabolism ; Phylogeny ; Plant Roots/*growth & development/metabolism ; Plants, Genetically Modified ; SNARE Proteins/genetics/*metabolism ; Saccharomyces cerevisiae/physiology ; Saccharomyces cerevisiae Proteins/metabolism ; Signal Transduction/*physiology ; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins ; }, abstract = {Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are key players in cellular trafficking and coordinate vital cellular processes, such as cytokinesis, pathogen defense, and ion transport regulation. With few exceptions, SNAREs are tail-anchored (TA) proteins, bearing a C-terminal hydrophobic domain that is essential for their membrane integration. Recently, the Guided Entry of Tail-anchored proteins (GET) pathway was described in mammalian and yeast cells that serve as a blueprint of TA protein insertion [Schuldiner M, et al. (2008) Cell 134(4):634-645; Stefanovic S, Hegde RS (2007) Cell 128(6):1147-1159]. This pathway consists of six proteins, with the cytosolic ATPase GET3 chaperoning the newly synthesized TA protein posttranslationally from the ribosome to the endoplasmic reticulum (ER) membrane. Structural and biochemical insights confirmed the potential of pathway components to facilitate membrane insertion, but the physiological significance in multicellular organisms remains to be resolved. Our phylogenetic analysis of 37 GET3 orthologs from 18 different species revealed the presence of two different GET3 clades. We identified and analyzed GET pathway components in Arabidopsis thaliana and found reduced root hair elongation in Atget lines, possibly as a result of reduced SNARE biogenesis. Overexpression of AtGET3a in a receptor knockout (KO) results in severe growth defects, suggesting presence of alternative insertion pathways while highlighting an intricate involvement for the GET pathway in cellular homeostasis of plants.}, } @article {pmid28094816, year = {2017}, author = {Cramer, JM and Pohlmann, D and Gomez, F and Mark, L and Kornegay, B and Hall, C and Siraliev-Perez, E and Walavalkar, NM and Sperlazza, MJ and Bilinovich, S and Prokop, JW and Hill, AL and Williams, DC}, title = {Methylation specific targeting of a chromatin remodeling complex from sponges to humans.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {40674}, pmid = {28094816}, issn = {2045-2322}, support = {K01 ES025435/ES/NIEHS NIH HHS/United States ; R01 GM098264/GM/NIGMS NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Amino Acid Sequence ; Animals ; *Chromatin Assembly and Disassembly ; DNA/chemistry/metabolism ; *DNA Methylation ; DNA-Binding Proteins/chemistry/genetics/metabolism ; Gene Knockdown Techniques ; Humans ; Models, Molecular ; Nucleic Acid Conformation ; Phenotype ; Porifera/*genetics/metabolism ; Protein Conformation ; }, abstract = {DNA cytosine methylation and methyl-cytosine binding domain (MBD) containing proteins are found throughout all vertebrate species studied to date. However, both the presence of DNA methylation and pattern of methylation varies among invertebrate species. Invertebrates generally have only a single MBD protein, MBD2/3, that does not always contain appropriate residues for selectively binding methylated DNA. Therefore, we sought to determine whether sponges, one of the most ancient extant metazoan lineages, possess an MBD2/3 capable of recognizing methylated DNA and recruiting the associated nucleosome remodeling and deacetylase (NuRD) complex. We find that Ephydatia muelleri has genes for each of the NuRD core components including an EmMBD2/3 that selectively binds methylated DNA. NMR analyses reveal a remarkably conserved binding mode, showing almost identical chemical shift changes between binding to methylated and unmethylated CpG dinucleotides. In addition, we find that EmMBD2/3 and EmGATAD2A/B proteins form a coiled-coil interaction known to be critical for the formation of NuRD. Finally, we show that knockdown of EmMBD2/3 expression disrupts normal cellular architecture and development of E. muelleri. These data support a model in which the MBD2/3 methylation-dependent functional role emerged with the earliest multicellular organisms and has been maintained to varying degrees across animal evolution.}, } @article {pmid28090383, year = {2016}, author = {Arensburger, P and Piégu, B and Bigot, Y}, title = {The future of transposable element annotation and their classification in the light of functional genomics - what we can learn from the fables of Jean de la Fontaine?.}, journal = {Mobile genetic elements}, volume = {6}, number = {6}, pages = {e1256852}, pmid = {28090383}, issn = {2159-2543}, abstract = {Transposable element (TE) science has been significantly influenced by the pioneering ideas of David Finnegan near the end of the last century, as well as by the classification systems that were subsequently developed. Today, whole genome TE annotation is mostly done using tools that were developed to aid gene annotation rather than to specifically study TEs. We argue that further progress in the TE field is impeded both by current TE classification schemes and by a failure to recognize that TE biology is fundamentally different from that of multicellular organisms. Novel genome wide TE annotation methods are helping to redefine our understanding of TE sequence origins and evolution. We briefly discuss some of these new methods as well as ideas for possible alternative classification schemes. Our hope is to encourage the formation of a society to organize a larger debate on these questions and to promote the adoption of standards for annotation and an improved TE classification.}, } @article {pmid28088333, year = {2017}, author = {Baffy, G}, title = {Mitochondrial uncoupling in cancer cells: Liabilities and opportunities.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1858}, number = {8}, pages = {655-664}, doi = {10.1016/j.bbabio.2017.01.005}, pmid = {28088333}, issn = {0005-2728}, mesh = {Animals ; Antineoplastic Agents/pharmacokinetics ; Cell Hypoxia ; Cell Line, Tumor ; Cellular Reprogramming ; Drug Resistance, Neoplasm/physiology ; Drug Synergism ; Energy Metabolism ; Humans ; Mitochondria/drug effects/*metabolism ; Mitochondrial Uncoupling Proteins/*physiology ; Models, Biological ; Neoplasm Proteins/physiology ; Neoplasms/drug therapy/*metabolism ; Oxidative Phosphorylation/drug effects ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Symbiosis ; Uncoupling Agents/pharmacology/therapeutic use ; }, abstract = {Acquisition of the endosymbiotic ancestor of mitochondria was a critical event in eukaryote evolution. Mitochondria offered an unparalleled source of metabolic energy through oxidative phosphorylation and allowed the development of multicellular life. However, as molecular oxygen had become the terminal electron acceptor in most eukaryotic cells, the electron transport chain proved to be the largest intracellular source of superoxide, contributing to macromolecular injury, aging, and cancer. Hence, the 'contract of endosymbiosis' represents a compromise between the possibilities and perils of multicellular life. Uncoupling proteins (UCPs), a group of the solute carrier family of transporters, may remove some of the physiologic constraints that link mitochondrial respiration and ATP synthesis by mediating inducible proton leak and limiting oxidative cell injury. This important property makes UCPs an ancient partner in the metabolic adaptation of cancer cells. Efforts are underway to explore the therapeutic opportunities stemming from the intriguing relationship of UCPs and cancer. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.}, } @article {pmid28078674, year = {2017}, author = {Bustamante, DE and Won, BY and Miller, KA and Cho, TO}, title = {Wilsonosiphonia gen. nov. (Rhodomelaceae, Rhodophyta) based on molecular and morpho-anatomical characters.}, journal = {Journal of phycology}, volume = {53}, number = {2}, pages = {368-380}, doi = {10.1111/jpy.12512}, pmid = {28078674}, issn = {1529-8817}, mesh = {DNA, Ribosomal ; Phylogeny ; Rhodophyta/classification/*genetics ; Sequence Analysis, DNA ; }, abstract = {Morphological, anatomical, and molecular sequence data were used to assess the establishment and phylogenetic position of the genus Wilsonosiphonia gen. nov. Phylogenies based on rbcL and concatenated rbcL and cox1 loci support recognition of Wilsonosiphonia gen. nov., sister to Herposiphonia. Diagnostic features for Wilsonosiphonia are rhizoids located at distal ends of pericentral cells and taproot-shaped multicellular tips of rhizoids. Wilsonosiphonia includes three species with diagnostic rbcL and cox1 sequences, Wilsonosiphonia fujiae sp. nov. (the generitype), W. howei comb. nov., and W. indica sp. nov. These three species resemble each other in external morphology, but W. fujiae is distinguished by having two tetrasporangia per segment rather than one, W. indica by having abundant and persistent trichoblasts, and W. howei by having few and deciduous trichoblasts.}, } @article {pmid28066387, year = {2016}, author = {Zhang, Z and Claessen, D and Rozen, DE}, title = {Understanding Microbial Divisions of Labor.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {2070}, pmid = {28066387}, issn = {1664-302X}, abstract = {Divisions of labor are ubiquitous in nature and can be found at nearly every level of biological organization, from the individuals of a shared society to the cells of a single multicellular organism. Many different types of microbes have also evolved a division of labor among its colony members. Here we review several examples of microbial divisions of labor, including cases from both multicellular and unicellular microbes. We first discuss evolutionary arguments, derived from kin selection, that allow divisions of labor to be maintained in the face of non-cooperative cheater cells. Next we examine the widespread natural variation within species in their expression of divisions of labor and compare this to the idea of optimal caste ratios in social insects. We highlight gaps in our understanding of microbial caste ratios and argue for a shift in emphasis from understanding the maintenance of divisions of labor, generally, to instead focusing on its specific ecological benefits for microbial genotypes and colonies. Thus, in addition to the canonical divisions of labor between, e.g., reproductive and vegetative tasks, we may also anticipate divisions of labor to evolve to reduce the costly production of secondary metabolites or secreted enzymes, ideas we consider in the context of streptomycetes. The study of microbial divisions of labor offers opportunities for new experimental and molecular insights across both well-studied and novel model systems.}, } @article {pmid28063828, year = {2017}, author = {Terauchi, M and Yamagishi, T and Hanyuda, T and Kawai, H}, title = {Genome-wide computational analysis of the secretome of brown algae (Phaeophyceae).}, journal = {Marine genomics}, volume = {32}, number = {}, pages = {49-59}, doi = {10.1016/j.margen.2016.12.002}, pmid = {28063828}, issn = {1876-7478}, mesh = {Amino Acid Sequence ; *Genome ; Genome-Wide Association Study ; Phaeophyta/*genetics ; Sequence Alignment ; }, abstract = {Brown algae have evolved complex multicellularity in the heterokont lineage. They are phylogenetically distant to land plants, fungi and animals. Especially, the members of Laminariales (so-called kelps) have developed highly differentiated tissues. Extracellular matrix (ECM) plays pivotal roles in a number of essential processes in multicellular organisms, such as cell adhesion, cell and tissue differentiations, cell-to-cell communication, and responses to environmental stimuli. In these processes, a set of extracellular secreted proteins called the secretome operates remodeling of the physicochemical nature of ECM and signal transduction by interacting with cell surface proteins and signaling molecules. Characterization of the secretome is a critical step to clarify the contributions of ECM to the multicellularity of brown algae. However, the identity of the brown algal secretome has been poorly understood. In order to reveal the repertory of the brown algal secretome and its involvement in the evolution of Laminariales, we conducted a genome-wide analysis of the brown algal secretome utilizing the published complete genome data of Ectocarpus siliculosus and Saccharina japonica as well as newly obtained RNA-seq data of seven laminarialean species (Agarum clathratum, Alaria crassifolia, Aureophycus aleuticus, Costaria costata, Pseudochorda nagaii, Saccharina angustata and Undaria pinnatifida) largely covering the laminarialean families. We established the in silico pipeline to systematically and accurately detect the secretome by combining multiple prediction algorithms for the N-terminal signal peptide and transmembrane domain within the protein sequence. From 16,189 proteins of E. siliculosus and 18,733 proteins of S. japonica, 552 and 964 proteins respectively were predicted to be classified as the secretome. Conserved domain analysis showed that the domain repertory were very similar to each other, and that of the brown algal secretome was partially common with that of the secretome of other multicellular organisms (land plants, fungi and animals). In the laminarialean species, it was estimated that the gene abundance and the domain architecture of putative ECM remodeling-related proteins were altered compared with those of E. siliculosus, and that the alteration started from the basal group of Laminariales. These results suggested that brown algae have developed their own secretome, and its functions became more elaborated in the more derived members in Laminariales.}, } @article {pmid28058671, year = {2017}, author = {Sommese, L and Zullo, A and Schiano, C and Mancini, FP and Napoli, C}, title = {Possible Muscle Repair in the Human Cardiovascular System.}, journal = {Stem cell reviews and reports}, volume = {13}, number = {2}, pages = {170-191}, pmid = {28058671}, issn = {2629-3277}, mesh = {Animals ; Cardiovascular Diseases/genetics/physiopathology/therapy ; Cardiovascular System/injuries/*metabolism/*physiopathology ; Cell Differentiation/genetics ; Cell Proliferation/genetics ; *Cellular Reprogramming ; Humans ; Myocardium/*metabolism/pathology ; Regeneration/genetics ; Regenerative Medicine/methods ; }, abstract = {The regenerative potential of tissues and organs could promote survival, extended lifespan and healthy life in multicellular organisms. Niches of adult stemness are widely distributed and lead to the anatomical and functional regeneration of the damaged organ. Conversely, muscular regeneration in mammals, and humans in particular, is very limited and not a single piece of muscle can fully regrow after a severe injury. Therefore, muscle repair after myocardial infarction is still a chimera. Recently, it has been recognized that epigenetics could play a role in tissue regrowth since it guarantees the maintenance of cellular identity in differentiated cells and, therefore, the stability of organs and tissues. The removal of these locks can shift a specific cell identity back to the stem-like one. Given the gradual loss of tissue renewal potential in the course of evolution, in the last few years many different attempts to retrieve such potential by means of cell therapy approaches have been performed in experimental models. Here we review pathways and mechanisms involved in the in vivo repair of cardiovascular muscle tissues in humans. Moreover, we address the ongoing research on mammalian cardiac muscle repair based on adult stem cell transplantation and pro-regenerative factor delivery. This latter issue, involving genetic manipulations of adult cells, paves the way for developing possible therapeutic strategies in the field of cardiovascular muscle repair.}, } @article {pmid28057261, year = {2017}, author = {Sebé-Pedrós, A and Ruiz-Trillo, I}, title = {Evolution and Classification of the T-Box Transcription Factor Family.}, journal = {Current topics in developmental biology}, volume = {122}, number = {}, pages = {1-26}, doi = {10.1016/bs.ctdb.2016.06.004}, pmid = {28057261}, issn = {1557-8933}, mesh = {Animals ; Base Sequence ; Conserved Sequence ; *Evolution, Molecular ; Fetal Proteins/chemistry/genetics ; Humans ; Morphogenesis ; Phylogeny ; T-Box Domain Proteins/chemistry/*classification/*genetics ; }, abstract = {T-box proteins are key developmental transcription factors in Metazoa. Until recently they were thought to be animal specific and many T-box classes were considered bilaterian specific. Recent genome data from both early-branching animals and their closest unicellular relatives have radically changed this scenario. Thus, we now know that T-box genes originated in premetazoans, being present in the genomes of some extant early-branching fungi and unicellular holozoans. Here, we update the evolutionary classification of T-box families and review the evolution of T-box function in early-branching animals (sponges, ctenophores, placozoans, and cnidarians) and nonmodel bilaterians. We show that concomitant with the origin of Metazoa, the T-box family radiated into the major known T-box classes. On the other hand, while functional studies are still missing for many T-box classes, the emerging picture is that T-box genes have key roles in multiple aspects of development and in adult terminal cell-type differentiation in different animal lineages. A paradigmatic example is that of Brachyury, the founding member of the T-box family, for which several studies indicate a widely conserved role in regulating cell motility in different animal lineages and probably even before the advent of animal multicellularity. Overall, we here review the evolutionary history of T-box genes from holozoans to animals and discuss both their functional diversity and conservation.}, } @article {pmid28049657, year = {2017}, author = {Macaisne, N and Liu, F and Scornet, D and Peters, AF and Lipinska, A and Perrineau, MM and Henry, A and Strittmatter, M and Coelho, SM and Cock, JM}, title = {The Ectocarpus IMMEDIATE UPRIGHT gene encodes a member of a novel family of cysteine-rich proteins with an unusual distribution across the eukaryotes.}, journal = {Development (Cambridge, England)}, volume = {144}, number = {3}, pages = {409-418}, doi = {10.1242/dev.141523}, pmid = {28049657}, issn = {1477-9129}, support = {638240/ERC_/European Research Council/International ; }, mesh = {Algal Proteins/antagonists & inhibitors/chemistry/*genetics ; Amino Acid Sequence ; Cloning, Molecular ; Cysteine/chemistry ; Evolution, Molecular ; Gene Expression Profiling ; Gene Transfer, Horizontal ; Models, Genetic ; Multigene Family ; Mutation ; Phaeophyta/*genetics/growth & development/virology ; Phylogeny ; RNA Interference ; Sequence Homology, Amino Acid ; Viral Proteins/chemistry/genetics ; }, abstract = {The sporophyte generation of the brown alga Ectocarpus sp. exhibits an unusual pattern of development compared with the majority of brown algae. The first cell division is symmetrical and the apical-basal axis is established late in development. In the immediate upright (imm) mutant, the initial cell undergoes an asymmetric division to immediately establish the apical-basal axis. We provide evidence which suggests that this phenotype corresponds to the ancestral state of the sporophyte. The IMM gene encodes a protein of unknown function that contains a repeated motif also found in the EsV-1-7 gene of the Ectocarpus virus EsV-1. Brown algae possess large families of EsV-1-7 domain genes but these genes are rare in other stramenopiles, suggesting that the expansion of this family might have been linked with the emergence of multicellular complexity. EsV-1-7 domain genes have a patchy distribution across eukaryotic supergroups and occur in several viral genomes, suggesting possible horizontal transfer during eukaryote evolution.}, } @article {pmid28048969, year = {2017}, author = {Veloso, FA}, title = {On the developmental self-regulatory dynamics and evolution of individuated multicellular organisms.}, journal = {Journal of theoretical biology}, volume = {417}, number = {}, pages = {84-99}, doi = {10.1016/j.jtbi.2016.12.025}, pmid = {28048969}, issn = {1095-8541}, mesh = {Animals ; *Biological Evolution ; Cell Differentiation/*genetics ; Cell Line ; Computational Biology ; Drosophila melanogaster ; *Epigenesis, Genetic ; *Gene Expression Regulation ; Histones/metabolism ; Humans ; Mice ; Protein Processing, Post-Translational ; RNA, Messenger/analysis ; Transcription Initiation Site ; }, abstract = {Changes in gene expression are thought to regulate the cell differentiation process intrinsically through complex epigenetic mechanisms. In fundamental terms, however, this assumed regulation refers only to the intricate propagation of changes in gene expression or else leads to non-explanatory regresses. The developmental self-regulatory dynamics and evolution of individuated multicellular organisms also lack a unified and falsifiable description. To fill this gap, I computationally analyzed publicly available high-throughput data of histone H3 post-translational modifications and mRNA abundance for different Homo sapiens, Mus musculus, and Drosophila melanogaster cell-type/developmental-period samples. My analysis of genomic regions adjacent to transcription start sites generated a profile from pairwise partial correlations between histone modifications controlling for the respective mRNA levels for each cell-type/developmental-period dataset. I found that these profiles, while explicitly uncorrelated with the respective transcriptional "identities" by construction, associate strongly with cell differentiation states. This association is not expected if cell differentiation is, in effect, regulated by epigenetic mechanisms. Based on these results, I propose a general, falsifiable theory of individuated multicellularity, which relies on the synergistic coupling across the extracellular space of two explicitly uncorrelated "self-organizing" systems constraining histone modification states at the same sites. This theory describes how the simplest multicellular individual-understood as an intrinsic, higher-order constraint-emerges from proliferating undifferentiated cells, and could explain the intrinsic regulation of gene transcriptional changes for cell differentiation and the evolution of individuated multicellular organisms.}, } @article {pmid30464998, year = {2017}, author = {Barthlott, W and Mail, M and Bhushan, B and Koch, K}, title = {Plant Surfaces: Structures and Functions for Biomimetic Innovations.}, journal = {Nano-micro letters}, volume = {9}, number = {2}, pages = {23}, pmid = {30464998}, issn = {2150-5551}, abstract = {An overview of plant surface structures and their evolution is presented. It combines surface chemistry and architecture with their functions and refers to possible biomimetic applications. Within some 3.5 billion years biological species evolved highly complex multifunctional surfaces for interacting with their environments: some 10 million living prototypes (i.e., estimated number of existing plants and animals) for engineers. The complexity of the hierarchical structures and their functionality in biological organisms surpasses all abiotic natural surfaces: even superhydrophobicity is restricted in nature to living organisms and was probably a key evolutionary step with the invasion of terrestrial habitats some 350-450 million years ago in plants and insects. Special attention should be paid to the fact that global environmental change implies a dramatic loss of species and with it the biological role models. Plants, the dominating group of organisms on our planet, are sessile organisms with large multifunctional surfaces and thus exhibit particular intriguing features. Superhydrophilicity and superhydrophobicity are focal points in this work. We estimate that superhydrophobic plant leaves (e.g., grasses) comprise in total an area of around 250 million km[2], which is about 50% of the total surface of our planet. A survey of structures and functions based on own examinations of almost 20,000 species is provided, for further references we refer to Barthlott et al. (Philos. Trans. R. Soc. A 374: 20160191, 1). A basic difference exists between aquatic non-vascular and land-living vascular plants; the latter exhibit a particular intriguing surface chemistry and architecture. The diversity of features is described in detail according to their hierarchical structural order. The first underlying and essential feature is the polymer cuticle superimposed by epicuticular wax and the curvature of single cells up to complex multicellular structures. A descriptive terminology for this diversity is provided. Simplified, the functions of plant surface characteristics may be grouped into six categories: (1) mechanical properties, (2) influence on reflection and absorption of spectral radiation, (3) reduction of water loss or increase of water uptake, moisture harvesting, (4) adhesion and non-adhesion (lotus effect, insect trapping), (5) drag and turbulence increase, or (6) air retention under water for drag reduction or gas exchange (Salvinia effect). This list is far from complete. A short overview of the history of bionics and the impressive spectrum of existing and anticipated biomimetic applications are provided. The major challenge for engineers and materials scientists, the durability of the fragile nanocoatings, is also discussed.}, } @article {pmid29687830, year = {2017}, author = {Cazzolla Gatti, R}, title = {Adaptation, Evolution And Reproduction Of Gaia By The Means Of Our Species.}, journal = {Theoretical biology forum}, volume = {110}, number = {1-2}, pages = {25-45}, doi = {10.19272/201711402003}, pmid = {29687830}, issn = {2282-2593}, mesh = {*Adaptation, Physiological ; Animals ; Atmosphere ; *Biological Evolution ; *Earth, Planet ; *Ecosystem ; *Evolution, Planetary ; Humans ; *Models, Biological ; *Reproduction ; Symbiosis ; }, abstract = {Nowadays, the idea that life affects the development of the planetary environment, and can, in turn, affect the future evolution of itself (in a coevolutionary way) is well-accepted. However, since the proposal of the Gaia hypothesis, there has been widespread criticism. Most of it is related to teleology, the absence of natural selection at a universal scale, and the lack of planetary reproduction. Some of the problems concerning the 'internal' logic of the idea have been resolved. Nevertheless, it is not sure whether Earth can be considered a unit of selection and (therefore) Gaia can adapt according to Darwinian evolution. After Lovelock and Margulis, Gaia has been considered a symbiotic planet composed of biotic (the biosphere) and abiotic (the geosphere-atmosphere) interacting with and coevolving elements. Here I propose why and suggest how a Gaian system should be considered alive in any evolutionary sense. I take into consideration the three principal criticisms and I analyse them following a logic-inductive reasoning. I use thought experiments and analogical arguments to analyse the rationale and the mechanisms by which Gaia evolves and may reproduce. This reasoning could allow rejecting the aforementioned criticisms as outdated and insufficient to discredit the main idea. I argue that without invoking teleology - so without any foresight or planning - a Gaian planet can be considered a coevolutionary system analogous to a multicellular body: a super-unit of selection. I describe different situations according to which Gaia is able to reproduce and transfer her planetary genome to other uninhabited or inhabited planets. Then I suggest that Gaia can face exclusion- competition-coexistence states depending on the fitness of her biota compared to those of the other reproducing biospheres. This demonstrates that Gaia can reproduce and evolve in competition-cooperation with other planets. Some deep implications arise from this evidence, also in light of the recent discovery of a new solar system with Earth-like planets by NASA.}, } @article {pmid28039083, year = {2017}, author = {Filippopoulou, K and Papaevgeniou, N and Lefaki, M and Paraskevopoulou, A and Biedermann, D and Křen, V and Chondrogianni, N}, title = {2,3-Dehydrosilybin A/B as a pro-longevity and anti-aggregation compound.}, journal = {Free radical biology & medicine}, volume = {103}, number = {}, pages = {256-267}, doi = {10.1016/j.freeradbiomed.2016.12.042}, pmid = {28039083}, issn = {1873-4596}, mesh = {Animals ; CHO Cells ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/metabolism ; Cell Line ; Cell Survival/drug effects ; Cricetinae ; Cricetulus ; Drug Evaluation, Preclinical ; Glucose Transport Proteins, Facilitative/metabolism ; Humans ; Longevity/*drug effects ; Oxidative Stress ; Protective Agents/*pharmacology ; Protein Aggregation, Pathological/*prevention & control ; Silybin ; Silymarin/*pharmacology ; }, abstract = {Aging is an unavoidable process characterized by gradual failure of homeostasis that constitutes a critical risk factor for several age-related disorders. It has been unveiled that manipulation of various key pathways may decelerate the aging progression and the triggering of age-related diseases. As a consequence, the identification of compounds, preferably natural-occurring, administered through diet, with lifespan-extending, anti-aggregation and anti-oxidation properties that in parallel exhibit negligible side-effects is the main goal in the battle against aging. Here we analyze the role of 2,3-dehydrosilybin A/B (DHS A/B), a minor component of silymarin used in a plethora of dietary supplements. This flavonolignan is well-known for its anti-oxidative and neuroprotective properties, among others. We demonstrate that DHS A/B confers oxidative stress resistance not only in human primary cells but also in the context of a multi-cellular aging model, namely Caenorhabditis elegans (C. elegans) where it also promotes lifespan extension. We reveal that these DHS A/B outcomes are FGT-1 and DAF-16 dependent. We additionally demonstrate the anti-aggregation properties of DHS A/B in human cells of nervous origin but also in nematode models of Alzheimer's disease (AD), eventually leading to decelerated progression of AD phenotype. Our results identify DHS A/B as the active component of silymarin extract and propose DHS A/B as a candidate anti-aging and anti-aggregation compound.}, } @article {pmid28036012, year = {2016}, author = {Pauzaite, T and Thacker, U and Tollitt, J and Copeland, NA}, title = {Emerging Roles for Ciz1 in Cell Cycle Regulation and as a Driver of Tumorigenesis.}, journal = {Biomolecules}, volume = {7}, number = {1}, pages = {}, pmid = {28036012}, issn = {2218-273X}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Carcinogenesis/*drug effects ; Cell Cycle ; *Cell Cycle Checkpoints ; Cell Transformation, Neoplastic ; Chromatin/metabolism ; Cyclin-Dependent Kinase 2/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; *DNA Replication ; Humans ; Mice ; Nuclear Proteins/*metabolism ; }, abstract = {Precise duplication of the genome is a prerequisite for the health and longevity of multicellular organisms. The temporal regulation of origin specification, replication licensing, and firing at replication origins is mediated by the cyclin-dependent kinases. Here the role of Cip1 interacting Zinc finger protein 1 (Ciz1) in regulation of cell cycle progression is discussed. Ciz1 contributes to regulation of the G1/S transition in mammalian cells. Ciz1 contacts the pre-replication complex (pre-RC) through cell division cycle 6 (Cdc6) interactions and aids localization of cyclin A- cyclin-dependent kinase 2 (CDK2) activity to chromatin and the nuclear matrix during initiation of DNA replication. We discuss evidence that Ciz1 serves as a kinase sensor that regulates both initiation of DNA replication and prevention of re-replication. Finally, the emerging role for Ciz1 in cancer biology is discussed. Ciz1 is overexpressed in common tumors and tumor growth is dependent on Ciz1 expression, suggesting that Ciz1 is a driver of tumor growth. We present evidence that Ciz1 may contribute to deregulation of the cell cycle due to its ability to alter the CDK activity thresholds that are permissive for initiation of DNA replication. We propose that Ciz1 may contribute to oncogenesis by induction of DNA replication stress and that Ciz1 may be a multifaceted target in cancer therapy.}, } @article {pmid28018750, year = {2016}, author = {Qiu, H and Yoon, HS and Bhattacharya, D}, title = {Red Algal Phylogenomics Provides a Robust Framework for Inferring Evolution of Key Metabolic Pathways.}, journal = {PLoS currents}, volume = {8}, number = {}, pages = {}, pmid = {28018750}, issn = {2157-3999}, abstract = {Red algae comprise an anciently diverged, species-rich phylum with morphologies that span unicells to large seaweeds. Here, leveraging a rich red algal genome and transcriptome dataset, we used 298 single-copy orthologous nuclear genes from 15 red algal species to erect a robust multi-gene phylogeny of Rhodophyta. This tree places red seaweeds (Bangiophyceae and Florideophyceae) at the base of the mesophilic red algae with the remaining non-seaweed mesophilic lineages forming a well-supported sister group. The early divergence of seaweeds contrasts with the evolution of multicellular land plants and brown algae that are nested among multiple, unicellular or filamentous sister lineages. Using this novel perspective on red algal evolution, we studied the evolution of the pathways for isoprenoid biosynthesis. This analysis revealed losses of the mevalonate pathway on at least three separate occasions in lineages that contain Cyanidioschyzon, Porphyridium, and Chondrus. Our results establish a framework for in-depth studies of the origin and evolution of genes and metabolic pathways in Rhodophyta.}, } @article {pmid28013230, year = {2017}, author = {Ohtani, M and Akiyoshi, N and Takenaka, Y and Sano, R and Demura, T}, title = {Evolution of plant conducting cells: perspectives from key regulators of vascular cell differentiation.}, journal = {Journal of experimental botany}, volume = {68}, number = {1}, pages = {17-26}, doi = {10.1093/jxb/erw473}, pmid = {28013230}, issn = {1460-2431}, mesh = {Biological Evolution ; Cell Differentiation/*physiology ; Embryophyta/cytology/growth & development/physiology ; Gene Expression Regulation, Developmental/physiology ; Gene Expression Regulation, Plant/physiology ; Phloem/*cytology/growth & development/physiology ; Xylem/*cytology/growth & development/physiology ; }, abstract = {One crucial problem that plants faced during their evolution, particularly during the transition to growth on land, was how to transport water, nutrients, metabolites, and small signaling molecules within a large, multicellular body. As a solution to this problem, land plants developed specific tissues for conducting molecules, called water-conducting cells (WCCs) and food-conducting cells (FCCs). The well-developed WCCs and FCCs in extant plants are the tracheary elements and sieve elements, respectively, which are found in vascular plants. Recent molecular genetic studies revealed that transcriptional networks regulate the differentiation of tracheary and sieve elements, and that the networks governing WCC differentiation are largely conserved among land plant species. In this review, we discuss the molecular evolution of plant conducting cells. By focusing on the evolution of the key transcription factors that regulate vascular cell differentiation, the NAC transcription factor VASCULAR-RELATED NAC-DOMAIN for WCCs and the MYB-coiled-coil (CC)-type transcription factor ALTERED PHLOEM DEVELOPMENT for sieve elements, we describe how land plants evolved molecular systems to produce the specialized cells that function as WCCs and FCCs.}, } @article {pmid28007886, year = {2017}, author = {Cleard, F and Wolle, D and Taverner, AM and Aoki, T and Deshpande, G and Andolfatto, P and Karch, F and Schedl, P}, title = {Different Evolutionary Strategies To Conserve Chromatin Boundary Function in the Bithorax Complex.}, journal = {Genetics}, volume = {205}, number = {2}, pages = {589-603}, pmid = {28007886}, issn = {1943-2631}, support = {R01 GM043432/GM/NIGMS NIH HHS/United States ; R01 GM083228/GM/NIGMS NIH HHS/United States ; R56 GM043432/GM/NIGMS NIH HHS/United States ; T32 HG003284/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Chromatin/*genetics ; Conserved Sequence ; Drosophila/*genetics ; Drosophila Proteins/genetics/metabolism ; *Evolution, Molecular ; *Insulator Elements ; Transcription Factors/genetics/metabolism ; }, abstract = {Chromatin boundary elements subdivide chromosomes in multicellular organisms into physically independent domains. In addition to this architectural function, these elements also play a critical role in gene regulation. Here we investigated the evolution of a Drosophila Bithorax complex boundary element called Fab-7, which is required for the proper parasegment specific expression of the homeotic Abd-B gene. Using a "gene" replacement strategy, we show that Fab-7 boundaries from two closely related species, D. erecta and D. yakuba, and a more distant species, D. pseudoobscura, are able to substitute for the melanogaster boundary. Consistent with this functional conservation, the two known Fab-7 boundary factors, Elba and LBC, have recognition sequences in the boundaries from all species. However, the strategies used for maintaining binding and function in the face of sequence divergence is different. The first is conventional, and depends upon conservation of the 8 bp Elba recognition sequence. The second is unconventional, and takes advantage of the unusually large and flexible sequence recognition properties of the LBC boundary factor, and the deployment of multiple LBC recognition elements in each boundary. In the former case, binding is lost when the recognition sequence is altered. In the latter case, sequence divergence is accompanied by changes in the number, relative affinity, and location of the LBC recognition elements.}, } @article {pmid27998811, year = {2016}, author = {Ramírez-Sánchez, O and Pérez-Rodríguez, P and Delaye, L and Tiessen, A}, title = {Plant Proteins Are Smaller Because They Are Encoded by Fewer Exons than Animal Proteins.}, journal = {Genomics, proteomics & bioinformatics}, volume = {14}, number = {6}, pages = {357-370}, pmid = {27998811}, issn = {2210-3244}, mesh = {Animals ; Bacteria/classification/genetics/metabolism ; Bacterial Proteins/chemistry/genetics/metabolism ; Eukaryota/classification/genetics/metabolism ; Evolution, Molecular ; Exons ; Genes, Plant ; Humans ; Linear Models ; Phylogeny ; Plant Proteins/*chemistry/genetics/metabolism ; Plants/classification/genetics/*metabolism ; Proteins/*chemistry/genetics/metabolism ; Symbiosis ; }, abstract = {Protein size is an important biochemical feature since longer proteins can harbor more domains and therefore can display more biological functionalities than shorter proteins. We found remarkable differences in protein length, exon structure, and domain count among different phylogenetic lineages. While eukaryotic proteins have an average size of 472 amino acid residues (aa), average protein sizes in plant genomes are smaller than those of animals and fungi. Proteins unique to plants are ∼81aa shorter than plant proteins conserved among other eukaryotic lineages. The smaller average size of plant proteins could neither be explained by endosymbiosis nor subcellular compartmentation nor exon size, but rather due to exon number. Metazoan proteins are encoded on average by ∼10 exons of small size [∼176 nucleotides (nt)]. Streptophyta have on average only ∼5.7 exons of medium size (∼230nt). Multicellular species code for large proteins by increasing the exon number, while most unicellular organisms employ rather larger exons (>400nt). Among subcellular compartments, membrane proteins are the largest (∼520aa), whereas the smallest proteins correspond to the gene ontology group of ribosome (∼240aa). Plant genes are encoded by half the number of exons and also contain fewer domains than animal proteins on average. Interestingly, endosymbiotic proteins that migrated to the plant nucleus became larger than their cyanobacterial orthologs. We thus conclude that plants have proteins larger than bacteria but smaller than animals or fungi. Compared to the average of eukaryotic species, plants have ∼34% more but ∼20% smaller proteins. This suggests that photosynthetic organisms are unique and deserve therefore special attention with regard to the evolutionary forces acting on their genomes and proteomes.}, } @article {pmid27996008, year = {2016}, author = {Zehr, JP and Shilova, IN and Farnelid, HM and Muñoz-Marín, MD and Turk-Kubo, KA}, title = {Unusual marine unicellular symbiosis with the nitrogen-fixing cyanobacterium UCYN-A.}, journal = {Nature microbiology}, volume = {2}, number = {}, pages = {16214}, doi = {10.1038/nmicrobiol.2016.214}, pmid = {27996008}, issn = {2058-5276}, abstract = {Nitrogen fixation - the reduction of dinitrogen (N2) gas to biologically available nitrogen (N) - is an important source of N for terrestrial and aquatic ecosystems. In terrestrial environments, N2-fixing symbioses involve multicellular plants, but in the marine environment these symbioses occur with unicellular planktonic algae. An unusual symbiosis between an uncultivated unicellular cyanobacterium (UCYN-A) and a haptophyte picoplankton alga was recently discovered in oligotrophic oceans. UCYN-A has a highly reduced genome, and exchanges fixed N for fixed carbon with its host. This symbiosis bears some resemblance to symbioses found in freshwater ecosystems. UCYN-A shares many core genes with the 'spheroid bodies' of Epithemia turgida and the endosymbionts of the amoeba Paulinella chromatophora. UCYN-A is widely distributed, and has diversified into a number of sublineages that could be ecotypes. Many questions remain regarding the physical and genetic mechanisms of the association, but UCYN-A is an intriguing model for contemplating the evolution of N2-fixing organelles.}, } @article {pmid27994131, year = {2017}, author = {Jill Harrison, C}, title = {Development and genetics in the evolution of land plant body plans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1713}, pages = {}, pmid = {27994131}, issn = {1471-2970}, support = {BB/L00224811//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Embryophyta/*genetics/*growth & development ; *Genes, Plant ; Germ Cells, Plant/growth & development ; }, abstract = {The colonization of land by plants shaped the terrestrial biosphere, the geosphere and global climates. The nature of morphological and molecular innovation driving land plant evolution has been an enigma for over 200 years. Recent phylogenetic and palaeobotanical advances jointly demonstrate that land plants evolved from freshwater algae and pinpoint key morphological innovations in plant evolution. In the haploid gametophyte phase of the plant life cycle, these include the innovation of mulitcellular forms with apical growth and multiple growth axes. In the diploid phase of the life cycle, multicellular axial sporophytes were an early innovation priming subsequent diversification of indeterminate branched forms with leaves and roots. Reverse and forward genetic approaches in newly emerging model systems are starting to identify the genetic basis of such innovations. The data place plant evo-devo research at the cusp of discovering the developmental and genetic changes driving the radiation of land plant body plans.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.}, } @article {pmid27994119, year = {2017}, author = {Cavalier-Smith, T}, title = {Origin of animal multicellularity: precursors, causes, consequences-the choanoflagellate/sponge transition, neurogenesis and the Cambrian explosion.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1713}, pages = {}, pmid = {27994119}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Choanoflagellata/growth & development/physiology ; Evolution, Molecular ; Invertebrates/growth & development/*physiology ; *Neurogenesis ; Porifera/growth & development/physiology ; }, abstract = {Evolving multicellularity is easy, especially in phototrophs and osmotrophs whose multicells feed like unicells. Evolving animals was much harder and unique; probably only one pathway via benthic 'zoophytes' with pelagic ciliated larvae allowed trophic continuity from phagocytic protozoa to gut-endowed animals. Choanoflagellate protozoa produced sponges. Converting sponge flask cells mediating larval settling to synaptically controlled nematocysts arguably made Cnidaria. I replace Haeckel's gastraea theory by a sponge/coelenterate/bilaterian pathway: Placozoa, hydrozoan diploblasty and ctenophores were secondary; stem anthozoan developmental mutations arguably independently generated coelomate bilateria and ctenophores. I emphasize animal origin's conceptual aspects (selective, developmental) related to feeding modes, cell structure, phylogeny of related protozoa, sequence evidence, ecology and palaeontology. Epithelia and connective tissue could evolve only by compensating for dramatically lower feeding efficiency that differentiation into non-choanocytes entails. Consequentially, larger bodies enabled filtering more water for bacterial food and harbouring photosynthetic bacteria, together adding more food than cell differentiation sacrificed. A hypothetical presponge of sessile triploblastic sheets (connective tissue sandwiched between two choanocyte epithelia) evolved oogamy through selection for larger dispersive ciliated larvae to accelerate benthic trophic competence and overgrowing protozoan competitors. Extinct Vendozoa might be elaborations of this organismal grade with choanocyte-bearing epithelia, before poriferan water channels and cnidarian gut/nematocysts/synapses evolved.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.}, } @article {pmid27994117, year = {2017}, author = {Bush, SJ and Chen, L and Tovar-Corona, JM and Urrutia, AO}, title = {Alternative splicing and the evolution of phenotypic novelty.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1713}, pages = {}, pmid = {27994117}, issn = {1471-2970}, mesh = {*Alternative Splicing ; Animals ; *Biological Evolution ; Evolution, Molecular ; Gene Duplication ; *Phenotype ; Transcriptome ; }, abstract = {Alternative splicing, a mechanism of post-transcriptional RNA processing whereby a single gene can encode multiple distinct transcripts, has been proposed to underlie morphological innovations in multicellular organisms. Genes with developmental functions are enriched for alternative splicing events, suggestive of a contribution of alternative splicing to developmental programmes. The role of alternative splicing as a source of transcript diversification has previously been compared to that of gene duplication, with the relationship between the two extensively explored. Alternative splicing is reduced following gene duplication with the retention of duplicate copies higher for genes which were alternatively spliced prior to duplication. Furthermore, and unlike the case for overall gene number, the proportion of alternatively spliced genes has also increased in line with the evolutionary diversification of cell types, suggesting alternative splicing may contribute to the complexity of developmental programmes. Together these observations suggest a prominent role for alternative splicing as a source of functional innovation. However, it is unknown whether the proliferation of alternative splicing events indeed reflects a functional expansion of the transcriptome or instead results from weaker selection acting on larger species, which tend to have a higher number of cell types and lower population sizes.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.}, } @article {pmid27984033, year = {2017}, author = {Malagoli, D and Ottaviani, E}, title = {Cross-talk among immune and neuroendocrine systems in molluscs and other invertebrate models.}, journal = {Hormones and behavior}, volume = {88}, number = {}, pages = {41-44}, doi = {10.1016/j.yhbeh.2016.10.015}, pmid = {27984033}, issn = {1095-6867}, mesh = {Animals ; *Biological Evolution ; Cell Transdifferentiation/physiology ; Homeostasis/physiology ; Immune System/immunology/*metabolism ; Invertebrates/immunology/*metabolism ; Mollusca/immunology/*metabolism ; Neurosecretory Systems/immunology/*metabolism ; }, abstract = {The comparison between immune and neuroendocrine systems in vertebrates and invertebrates suggest an ancient origin and a high degree of conservation for the mechanisms underlying the integration between immune and stress responses. This suggests that in both vertebrates and invertebrates the stress response involves the integrated network of soluble mediators (e.g., neurotransmitters, hormones and cytokines) and cell functions (e.g., chemotaxis and phagocytosis), that interact with a common objective, i.e., the maintenance of body homeostasis. During evolution, several changes observed in the stress response of more complex taxa could be the result of new roles of ancestral molecules, such as ancient immune mediators may have been recruited as neurotransmitters and hormones, or vice versa. We review older and recent evidence suggesting that immune and neuro-endocrine functions during the stress response were deeply intertwined already at the dawn of multicellular organisms. These observations found relevant reflections in the demonstration that immune cells can transdifferentiate in olfactory neurons in crayfish and the recently re-proposed neural transdifferentiation in humans.}, } @article {pmid27980068, year = {2017}, author = {Ihara, S and Nakayama, S and Murakami, Y and Suzuki, E and Asakawa, M and Kinoshita, T and Sawa, H}, title = {PIGN prevents protein aggregation in the endoplasmic reticulum independently of its function in the GPI synthesis.}, journal = {Journal of cell science}, volume = {130}, number = {3}, pages = {602-613}, doi = {10.1242/jcs.196717}, pmid = {27980068}, issn = {1477-9137}, mesh = {Animals ; Caenorhabditis elegans/cytology/*metabolism/ultrastructure ; Caenorhabditis elegans Proteins/*metabolism ; Conserved Sequence ; Endoplasmic Reticulum/*metabolism/ultrastructure ; Evolution, Molecular ; Glycosylphosphatidylinositols/*metabolism ; HEK293 Cells ; Humans ; Intracellular Membranes/metabolism ; Intracellular Space/metabolism ; Mutation/genetics ; Phosphotransferases/chemistry/*metabolism ; *Protein Aggregates ; Sequence Homology, Amino Acid ; }, abstract = {Quality control of proteins in the endoplasmic reticulum (ER) is essential for ensuring the integrity of secretory proteins before their release into the extracellular space. Secretory proteins that fail to pass quality control form aggregates. Here we show the PIGN-1/PIGN is required for quality control in Caenorhabditis elegans and in mammalian cells. In C. elegans pign-1 mutants, several proteins fail to be secreted and instead form abnormal aggregation. PIGN-knockout HEK293 cells also showed similar protein aggregation. Although PIGN-1/PIGN is responsible for glycosylphosphatidylinositol (GPI)-anchor biosynthesis in the ER, certain mutations in C. elegans pign-1 caused protein aggregation in the ER without affecting GPI-anchor biosynthesis. These results show that PIGN-1/PIGN has a conserved and non-canonical function to prevent deleterious protein aggregation in the ER independently of the GPI-anchor biosynthesis. PIGN is a causative gene for some human diseases including multiple congenital seizure-related syndrome (MCAHS1). Two pign-1 mutations created by CRISPR/Cas9 that correspond to MCAHS1 also cause protein aggregation in the ER, implying that the dysfunction of the PIGN non-canonical function might affect symptoms of MCAHS1 and potentially those of other diseases.}, } @article {pmid27979655, year = {2017}, author = {Lalucque, H and Malagnac, F and Green, K and Gautier, V and Grognet, P and Chan Ho Tong, L and Scott, B and Silar, P}, title = {IDC2 and IDC3, two genes involved in cell non-autonomous signaling of fruiting body development in the model fungus Podospora anserina.}, journal = {Developmental biology}, volume = {421}, number = {2}, pages = {126-138}, doi = {10.1016/j.ydbio.2016.12.016}, pmid = {27979655}, issn = {1095-564X}, mesh = {Amino Acid Sequence ; Blotting, Western ; Cellulose/pharmacology ; Conserved Sequence ; Cysteine/metabolism ; Evolution, Molecular ; Fruiting Bodies, Fungal/*genetics/*growth & development ; Fungal Proteins/chemistry/*genetics/metabolism ; Gene Deletion ; *Genes, Fungal ; Genetic Complementation Test ; Green Fluorescent Proteins/metabolism ; Mosaicism ; Mycelium/metabolism ; Phenotype ; Phosphorylation/drug effects ; Podospora/*genetics/*growth & development ; Signal Transduction/*genetics ; Subcellular Fractions/metabolism ; Vacuoles/metabolism ; }, abstract = {Filamentous ascomycetes produce complex multicellular structures during sexual reproduction. Little is known about the genetic pathways enabling the construction of such structures. Here, with a combination of classical and reverse genetic methods, as well as genetic mosaic and graft analyses, we identify and provide evidence for key roles for two genes during the formation of perithecia, the sexual fruiting bodies, of the filamentous fungus Podospora anserina. Data indicate that the proteins coded by these two genes function cell-non-autonomously and that their activity depends upon conserved cysteines, making them good candidate for being involved in the transmission of a reactive oxygen species (ROS) signal generated by the PaNox1 NADPH oxidase inside the maturing fruiting body towards the PaMpk1 MAP kinase, which is located inside the underlying mycelium, in which nutrients are stored. These data provide important new insights to our understanding of how fungi build multicellular structures.}, } @article {pmid27967109, year = {2016}, author = {Kirkegaard, JB and Goldstein, RE}, title = {Filter-feeding, near-field flows, and the morphologies of colonial choanoflagellates.}, journal = {Physical review. E}, volume = {94}, number = {5-1}, pages = {052401}, pmid = {27967109}, issn = {2470-0053}, support = {//Wellcome Trust/United Kingdom ; 097855//Wellcome Trust/United Kingdom ; }, mesh = {Choanoflagellata/*cytology/*physiology ; Feeding Behavior/*physiology ; *Water Movements ; }, abstract = {Efficient uptake of prey and nutrients from the environment is an important component in the fitness of all microorganisms, and its dependence on size may reveal clues to the origins of evolutionary transitions to multicellularity. Because potential benefits in uptake rates must be viewed in the context of other costs and benefits of size, such as varying predation rates and the increased metabolic costs associated with larger and more complex body plans, the uptake rate itself is not necessarily that which is optimized by evolution. Uptake rates can be strongly dependent on local organism geometry and its swimming speed, providing selective pressure for particular arrangements. Here we examine these issues for choanoflagellates, filter-feeding microorganisms that are the closest relatives of the animals. We explore the different morphological variations of the choanoflagellate Salpingoeca rosetta, which can exist as a swimming cell, as a sessile thecate cell, and as colonies of cells in various shapes. In the absence of other requirements and in a homogeneously nutritious environment, we find that the optimal strategy to maximize filter-feeding by the collar of microvilli is to swim fast, which favors swimming unicells. In large external flows, the sessile thecate cell becomes advantageous. Effects of prey diffusion are discussed and also found to be to the advantage of the swimming unicell.}, } @article {pmid27965457, year = {2017}, author = {Däster, S and Amatruda, N and Calabrese, D and Ivanek, R and Turrini, E and Droeser, RA and Zajac, P and Fimognari, C and Spagnoli, GC and Iezzi, G and Mele, V and Muraro, MG}, title = {Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment.}, journal = {Oncotarget}, volume = {8}, number = {1}, pages = {1725-1736}, pmid = {27965457}, issn = {1949-2553}, mesh = {Animals ; Antimetabolites, Antineoplastic/*pharmacology ; Cell Hypoxia/*physiology ; Colorectal Neoplasms/drug therapy/*pathology ; Drug Resistance, Neoplasm/*physiology ; Fluorouracil/*pharmacology ; Gene Expression Profiling ; HCT116 Cells ; HT29 Cells ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Necrosis/*pathology ; Oxygen/metabolism ; Spheroids, Cellular/*physiology ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {Culture of cancerous cells in standard monolayer conditions poorly mirrors growth in three-dimensional architectures typically observed in a wide majority of cancers of different histological origin. Multicellular tumor spheroid (MCTS) culture models were developed to mimic these features. However, in vivo tumor growth is also characterized by the presence of ischemic and necrotic areas generated by oxygenation gradients and differential access to nutrients. Hypoxia and necrosis play key roles in tumor progression and resistance to treatment. To provide in vitro models recapitulating these events in highly controlled and standardized conditions, we have generated colorectal cancer (CRC) cell spheroids of different sizes and analyzed their gene expression profiles and sensitivity to treatment with 5FU, currently used in therapeutic protocols. Here we identify three MCTS stages, corresponding to defined spheroid sizes, characterized by normoxia, hypoxia, and hypoxia plus necrosis, respectively. Importantly, we show that MCTS including both hypoxic and necrotic areas most closely mimic gene expression profiles of in vivo-developing tumors and display the highest resistance to 5FU. Taken together, our data indicate that MCTS may mimic in vitro generation of ischemic and necrotic areas in highly standardized and controlled conditions, thereby qualifying as relevant models for drug screening purposes.}, } @article {pmid27939723, year = {2017}, author = {Lu, X and Xiang, Y and Yang, G and Zhang, L and Wang, H and Zhong, S}, title = {Transcriptomic characterization of zebrafish larvae in response to mercury exposure.}, journal = {Comparative biochemistry and physiology. Toxicology & pharmacology : CBP}, volume = {192}, number = {}, pages = {40-49}, doi = {10.1016/j.cbpc.2016.12.006}, pmid = {27939723}, issn = {1532-0456}, mesh = {ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics/metabolism ; Animals ; Biological Transport ; Computational Biology ; Databases, Genetic ; Gene Expression Profiling/methods ; Gene Expression Regulation, Developmental/*drug effects ; Gene Regulatory Networks ; High-Throughput Nucleotide Sequencing ; LLC-PK1 Cells ; Larva/*drug effects/genetics ; Mercuric Chloride/metabolism/*toxicity ; Swine ; Time Factors ; Transcription, Genetic/*drug effects ; Transfection ; Water Pollutants, Chemical/metabolism/*toxicity ; Zebrafish/*genetics/metabolism ; Zebrafish Proteins/*genetics/metabolism ; }, abstract = {Mercury is a widespread toxicant in aquatic environment that can cause deleterious effects on fish. Although a number of mercury-regulated genes have been investigated in adult fish, the transcriptional responses of fish larvae to acute mercury exposure are not well understood. In this study, RNA sequencing was used to examine the transcriptional changes in developing zebrafish larvae under a low concentration of mercuric chloride exposure from 24 to 120hpf. Our initial results showed that a total of 142.59 million raw reads were obtained from sequencing libraries and about 86% of the processed reads were mapped to the reference genome of zebrafish. Differential expression analysis identified 391 up- and 87 down-regulated genes. Gene ontology enrichment analysis revealed that most of the differential expressed genes are closely related to the regulation of cellular process, metabolic process, multicellular organismal process, biological regulation, pigmentation, and response to stimulus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated that antigen processing and presentation was the most significantly enriched pathway. Moreover, we characterized a novel and sensitive mercury-induced ABCB (ATP- binding cassette B subfamily) transporter gene - abcb5. This gene is localized on zebrafish chromosome 16 and contains a 4014bp open-reading frame. The deduced polypeptide is composed of 1337 amino acids and possesses most of functional domains and critical residues defined in human and mouse ABCB5/Abcb5. Functional analysis in vitro demonstrated that overexpression of zebrafish abcb5 gene can significantly decrease the cytotoxicity of mercury in LLC-PK1 cells, implying it is a potential efflux transporter of mercury. Thus, these findings provide useful insights to help further understand the transcriptional response and detoxification ability of zebrafish larvae following acute exposure to mercury.}, } @article {pmid27936291, year = {2017}, author = {Hughes, KA and Leips, J}, title = {Pleiotropy, constraint, and modularity in the evolution of life histories: insights from genomic analyses.}, journal = {Annals of the New York Academy of Sciences}, volume = {1389}, number = {1}, pages = {76-91}, pmid = {27936291}, issn = {1749-6632}, support = {F32 GM016990/GM/NIGMS NIH HHS/United States ; R01 DK084219/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Drosophila melanogaster ; *Genetic Pleiotropy ; *Genetic Variation ; *Genetics, Population ; Genome ; Genome-Wide Association Study ; *Genomics ; Humans ; Plants ; Quantitative Trait Loci ; Selection, Genetic ; }, abstract = {Multicellular organisms display an enormous range of life history (LH) strategies and present an evolutionary conundrum; despite strong natural selection, LH traits are characterized by high levels of genetic variation. To understand the evolution of life histories and maintenance of this variation, the specific phenotypic effects of segregating alleles and the genetic networks in which they act need to be elucidated. In particular, the extent to which LH evolution is constrained by the pleiotropy of alleles contributing to LH variation is generally unknown. Here, we review recent empirical results that shed light on this question, with an emphasis on studies employing genomic analyses. While genome-scale analyses are increasingly practical and affordable, they face limitations of genetic resolution and statistical power. We describe new research approaches that we believe can produce new insights and evaluate their promise and applicability to different kinds of organisms. Two approaches seem particularly promising: experiments that manipulate selection in multiple dimensions and measure phenotypic and genomic response and analytical approaches that take into account genome-wide associations between markers and phenotypes, rather than applying a traditional marker-by-marker approach.}, } @article {pmid27934708, year = {2016}, author = {Jones, JD and Vance, RE and Dangl, JL}, title = {Intracellular innate immune surveillance devices in plants and animals.}, journal = {Science (New York, N.Y.)}, volume = {354}, number = {6316}, pages = {}, doi = {10.1126/science.aaf6395}, pmid = {27934708}, issn = {1095-9203}, support = {BB/K003550/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M003809/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M008193/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Evolution, Molecular ; Host-Pathogen Interactions ; *Immunity, Innate ; *Immunologic Surveillance ; NLR Proteins/chemistry/genetics/*immunology ; Plant Diseases/immunology/microbiology ; Plants/*immunology/*microbiology ; Protein Domains ; }, abstract = {Multicellular eukaryotes coevolve with microbial pathogens, which exert strong selective pressure on the immune systems of their hosts. Plants and animals use intracellular proteins of the nucleotide-binding domain, leucine-rich repeat (NLR) superfamily to detect many types of microbial pathogens. The NLR domain architecture likely evolved independently and convergently in each kingdom, and the molecular mechanisms of pathogen detection by plant and animal NLRs have long been considered to be distinct. However, microbial recognition mechanisms overlap, and it is now possible to discern important key trans-kingdom principles of NLR-dependent immune function. Here, we attempt to articulate these principles. We propose that the NLR architecture has evolved for pathogen-sensing in diverse organisms because of its utility as a tightly folded "hair trigger" device into which a virtually limitless number of microbial detection platforms can be integrated. Recent findings suggest means to rationally design novel recognition capabilities to counter disease.}, } @article {pmid27917322, year = {2016}, author = {Grishaeva, TM and Kulichenko, D and Bogdanov, YF}, title = {Bioinformatical analysis of eukaryotic shugoshins reveals meiosis-specific features of vertebrate shugoshins.}, journal = {PeerJ}, volume = {4}, number = {}, pages = {e2736}, pmid = {27917322}, issn = {2167-8359}, abstract = {BACKGROUND: Shugoshins (SGOs) are proteins that protect cohesins located at the centromeres of sister chromatids from their early cleavage during mitosis and meiosis in plants, fungi, and animals. Their function is to prevent premature sister-chromatid disjunction and segregation. The study focused on the structural differences among SGOs acting during mitosis and meiosis that cause differences in chromosome behavior in these two types of cell division in different organisms.

METHODS: A bioinformatical analysis of protein domains, conserved amino acid motifs, and physicochemical properties of 32 proteins from 25 species of plants, fungi, and animals was performed.

RESULTS: We identified a C-terminal amino acid motif that is highly evolutionarily conserved among the SGOs protecting centromere cohesion of sister chromatids in meiotic anaphase I, but not among mitotic SGOs. This meiotic motif is arginine-rich in vertebrates. SGOs differ in different eukaryotic kingdoms by the sets and locations of amino acid motifs and the number of α-helical regions in the protein molecule.

DISCUSSION: These structural differences between meiotic and mitotic SGOs probably could be responsible for the prolonged SGOs resistance to degradation during meiotic metaphase I and anaphase I. We suggest that the "arginine comb" in C-end meiotic motifs is capable of interaction by hydrogen bonds with guanine bases in the minor groove of DNA helix, thus protecting SGOs from hydrolysis. Our findings support independent evolution of meiosis in different lineages of multicellular organisms.}, } @article {pmid27916428, year = {2017}, author = {Kroos, L}, title = {Highly Signal-Responsive Gene Regulatory Network Governing Myxococcus Development.}, journal = {Trends in genetics : TIG}, volume = {33}, number = {1}, pages = {3-15}, pmid = {27916428}, issn = {0168-9525}, support = {R01 GM043585/GM/NIGMS NIH HHS/United States ; }, mesh = {Gene Expression Regulation, Bacterial/genetics ; Gene Regulatory Networks/*genetics ; Mutation ; Myxococcus xanthus/*genetics/growth & development ; Signal Transduction/*genetics ; Spores, Bacterial/*genetics ; Transcriptional Activation/genetics ; }, abstract = {The bacterium Myxococcus xanthus undergoes multicellular development when starved. Thousands of cells build mounds in which some differentiate into spores. This remarkable feat and the genetic tractability of Myxococcus provide a unique opportunity to understand the evolution of gene regulatory networks (GRNs). Recent work has revealed a GRN involving interconnected cascades of signal-responsive transcriptional activators. Initially, starvation-induced intracellular signals direct changes in gene expression. Subsequently, self-generated extracellular signals provide morphological cues that regulate certain transcriptional activators. However, signals for many of the activators remain to be discovered. A key insight is that activators often work combinatorially, allowing signal integration. The Myxococcus GRN differs strikingly from those governing sporulation of Bacillus and Streptomyces, suggesting that Myxococcus evolved a highly signal-responsive GRN to enable complex multicellular development.}, } @article {pmid27913751, year = {2017}, author = {Wu, Y and Gao, B and Zhu, S}, title = {New fungal defensin-like peptides provide evidence for fold change of proteins in evolution.}, journal = {Bioscience reports}, volume = {37}, number = {1}, pages = {}, pmid = {27913751}, issn = {1573-4935}, mesh = {Amino Acid Sequence ; Ascomycota/*chemistry/genetics ; Cysteine/chemistry/genetics ; Defensins/*chemistry/genetics ; Evolution, Molecular ; Fungal Proteins/*chemistry/genetics ; Genes, Fungal ; Models, Molecular ; Protein Conformation, alpha-Helical ; Protein Conformation, beta-Strand ; Protein Folding ; Sequence Alignment ; }, abstract = {Defensins containing a consensus cystine framework, Cys[1]…Cys[2]X3Cys[3]…Cys[4]… Cys[5]X1Cys[6] (X, any amino acid except Cys; …, variable residue numbers), are extensively distributed in a variety of multicellular organisms (plants, fungi and invertebrates) and essentially involved in immunity as microbicidal agents. This framework is a prerequisite for forming the cysteine-stabilized α-helix and β-sheet (CSαβ) fold, in which the two invariant motifs, Cys[2]X3Cys[3]/Cys[5]X1Cys[6], are key determinants of fold formation. By using a computational genomics approach, we identified a large superfamily of fungal defensin-like peptides (fDLPs) in the phytopathogenic fungal genus - Zymoseptoria, which includes 132 structurally typical and 63 atypical members. These atypical fDLPs exhibit an altered cystine framework and accompanying fold change associated with their secondary structure elements and disulfide bridge patterns, as identified by protein structure modelling. Despite this, they definitely are homologous with the typical fDLPs in view of their precise gene structure conservation and identical precursor organization. Sequence and structural analyses combined with functional data suggest that most of Zymoseptoria fDLPs might have lost their antimicrobial activity. The present study provides a clear example of fold change in the evolution of proteins and is valuable in establishing remote homology among peptide superfamily members with different folds.}, } @article {pmid27903631, year = {2017}, author = {Dettman, JR and Rodrigue, N and Schoustra, SE and Kassen, R}, title = {Genomics of Compensatory Adaptation in Experimental Populations of Aspergillus nidulans.}, journal = {G3 (Bethesda, Md.)}, volume = {7}, number = {2}, pages = {427-436}, pmid = {27903631}, issn = {2160-1836}, support = {//CIHR/Canada ; }, mesh = {Adaptation, Physiological/*genetics ; Aspergillus nidulans/drug effects/*genetics/growth & development ; Dioxoles/pharmacology ; Drug Resistance, Fungal ; *Evolution, Molecular ; *Genetic Fitness ; Genome, Fungal ; Genomics ; Osmotic Pressure/physiology ; Pyrroles/pharmacology ; }, abstract = {Knowledge of the number and nature of genetic changes responsible for adaptation is essential for understanding and predicting evolutionary trajectories. Here, we study the genomic basis of compensatory adaptation to the fitness cost of fungicide resistance in experimentally evolved strains of the filamentous fungus Aspergillus nidulans The original selection experiment tracked the fitness recovery of lines founded by an ancestral strain that was resistant to fludioxonil, but paid a fitness cost in the absence of the fungicide. We obtained whole-genome sequence data for the ancestral A. nidulans strain and eight experimentally evolved strains. We find that fludioxonil resistance in the ancestor was likely conferred by a mutation in histidine kinase nikA, part of the two-component signal transduction system of the high-osmolarity glycerol (HOG) stress response pathway. To compensate for the pleiotropic negative effects of the resistance mutation, the subsequent fitness gains observed in the evolved lines were likely caused by secondary modification of HOG pathway activity. Candidate genes for the compensatory fitness increases were significantly overrepresented by stress response functions, and some were specifically associated with the HOG pathway itself. Parallel evolution at the gene level was rare among evolved lines. There was a positive relationship between the predicted number of adaptive steps, estimated from fitness data, and the number of genomic mutations, determined by whole-genome sequencing. However, the number of genomic mutations was, on average, 8.45 times greater than the number of adaptive steps inferred from fitness data. This research expands our understanding of the genetic basis of adaptation in multicellular eukaryotes and lays out a framework for future work on the genomics of compensatory adaptation in A. nidulans.}, } @article {pmid27889635, year = {2017}, author = {Brunkard, JO and Zambryski, PC}, title = {Plasmodesmata enable multicellularity: new insights into their evolution, biogenesis, and functions in development and immunity.}, journal = {Current opinion in plant biology}, volume = {35}, number = {}, pages = {76-83}, doi = {10.1016/j.pbi.2016.11.007}, pmid = {27889635}, issn = {1879-0356}, mesh = {*Biological Evolution ; *Organelle Biogenesis ; Plant Development ; Plant Immunity ; *Plant Physiological Phenomena ; Plasmodesmata/*physiology ; }, abstract = {Plant cells are connected by plasmodesmata (PD), cytosolic bridges that allow molecules to freely move across the cell wall. Recently resolved relationships among land plants and their algal relatives reveal that land plants evolved PD independently from algae. Proteomic and genetic screens illuminate new dimensions of the structural and regulatory pathways that control PD biogenesis. Biochemical studies demonstrate that immunological signals induce systemic defenses by moving from diseased cells through PD; subsequently, PD transport is restricted to quarantine diseased cells. Here, we review our expanding knowledge of the roles of PD in plant development, physiology, and immunity.}, } @article {pmid27888167, year = {2017}, author = {Liao, BK and Oates, AC}, title = {Delta-Notch signalling in segmentation.}, journal = {Arthropod structure & development}, volume = {46}, number = {3}, pages = {429-447}, pmid = {27888167}, issn = {1873-5495}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Body Patterning/genetics/*physiology ; Gene Expression Regulation, Developmental ; Phylogeny ; Receptors, Notch/genetics/*metabolism ; *Signal Transduction ; }, abstract = {Modular body organization is found widely across multicellular organisms, and some of them form repetitive modular structures via the process of segmentation. It's vastly interesting to understand how these regularly repeated structures are robustly generated from the underlying noise in biomolecular interactions. Recent studies from arthropods reveal similarities in segmentation mechanisms with vertebrates, and raise the possibility that the three phylogenetic clades, annelids, arthropods and chordates, might share homology in this process from a bilaterian ancestor. Here, we discuss vertebrate segmentation with particular emphasis on the role of the Notch intercellular signalling pathway. We introduce vertebrate segmentation and Notch signalling, pointing out historical milestones, then describe existing models for the Notch pathway in the synchronization of noisy neighbouring oscillators, and a new role in the modulation of gene expression wave patterns. We ask what functions Notch signalling may have in arthropod segmentation and explore the relationship between Notch-mediated lateral inhibition and synchronization. Finally, we propose open questions and technical challenges to guide future investigations into Notch signalling in segmentation.}, } @article {pmid27886385, year = {2017}, author = {Frangedakis, E and Saint-Marcoux, D and Moody, LA and Rabbinowitsch, E and Langdale, JA}, title = {Nonreciprocal complementation of KNOX gene function in land plants.}, journal = {The New phytologist}, volume = {216}, number = {2}, pages = {591-604}, pmid = {27886385}, issn = {1469-8137}, mesh = {Bayes Theorem ; Embryophyta/*genetics ; Evolution, Molecular ; Gene Duplication ; *Genes, Plant ; *Genetic Complementation Test ; Likelihood Functions ; Loss of Function Mutation/genetics ; Phylogeny ; Plant Proteins/genetics/metabolism ; Plants, Genetically Modified ; Species Specificity ; Transgenes ; }, abstract = {Class I KNOTTED-LIKE HOMEOBOX (KNOX) proteins regulate development of the multicellular diploid sporophyte in both mosses and flowering plants; however, the morphological context in which they function differs. In order to determine how Class I KNOX function was modified as land plants evolved, phylogenetic analyses and cross-species complementation assays were performed. Our data reveal that a duplication within the charophyte sister group to land plants led to distinct Class I and Class II KNOX gene families. Subsequently, Class I sequences diverged substantially in the nonvascular bryophyte groups (liverworts, mosses and hornworts), with moss sequences being most similar to those in vascular plants. Despite this similarity, moss mutants were not complemented by vascular plant KNOX genes. Conversely, the Arabidopsis brevipedicellus (bp-9) mutant was complemented by the PpMKN2 gene from the moss Physcomitrella patens. Lycophyte KNOX genes also complemented bp-9 whereas fern genes only partially complemented the mutant. This lycophyte/fern distinction is mirrored in the phylogeny of KNOX-interacting BELL proteins, in that a gene duplication occurred after divergence of the two groups. Together, our results imply that the moss MKN2 protein can function in a broader developmental context than vascular plant KNOX proteins, the narrower scope having evolved progressively as lycophytes, ferns and flowering plants diverged.}, } @article {pmid27882869, year = {2016}, author = {Kirkegaard, JB and Bouillant, A and Marron, AO and Leptos, KC and Goldstein, RE}, title = {Aerotaxis in the closest relatives of animals.}, journal = {eLife}, volume = {5}, number = {}, pages = {}, pmid = {27882869}, issn = {2050-084X}, support = {097855/WT_/Wellcome Trust/United Kingdom ; 247333/ERC_/European Research Council/International ; 097855/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Chemotaxis ; Choanoflagellata/*drug effects/*physiology ; Lab-On-A-Chip Devices ; Oxygen/*metabolism ; }, abstract = {As the closest unicellular relatives of animals, choanoflagellates serve as useful model organisms for understanding the evolution of animal multicellularity. An important factor in animal evolution was the increasing ocean oxygen levels in the Precambrian, which are thought to have influenced the emergence of complex multicellular life. As a first step in addressing these conditions, we study here the response of the colony-forming choanoflagellate Salpingoeca rosetta to oxygen gradients. Using a microfluidic device that allows spatio-temporal variations in oxygen concentrations, we report the discovery that S. rosetta displays positive aerotaxis. Analysis of the spatial population distributions provides evidence for logarithmic sensing of oxygen, which enhances sensing in low oxygen neighborhoods. Analysis of search strategy models on the experimental colony trajectories finds that choanoflagellate aerotaxis is consistent with stochastic navigation, the statistics of which are captured using an effective continuous version based on classical run-and-tumble chemotaxis.}, } @article {pmid27880891, year = {2017}, author = {Guzman, A and Sánchez Alemany, V and Nguyen, Y and Zhang, CR and Kaufman, LJ}, title = {A novel 3D in vitro metastasis model elucidates differential invasive strategies during and after breaching basement membrane.}, journal = {Biomaterials}, volume = {115}, number = {}, pages = {19-29}, doi = {10.1016/j.biomaterials.2016.11.014}, pmid = {27880891}, issn = {1878-5905}, mesh = {Batch Cell Culture Techniques/*methods ; Cell Line, Tumor ; Cell Membrane/metabolism/*pathology ; Extracellular Matrix/metabolism/pathology ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasms, Experimental/metabolism/*pathology/*secondary ; *Printing, Three-Dimensional ; *Tissue Scaffolds ; }, abstract = {Invasive breast cancer and other tumors of epithelial origin must breach a layer of basement membrane (BM) that surrounds the primary tumor before invading into the adjacent extracellular matrix. To analyze invasive strategies of breast cancer cells during BM breaching and subsequent invasion into a collagen I-rich extracellular matrix (ECM), we developed a physiologically relevant 3D in vitro model that recreates the architecture of a solid tumor with an intact, degradable, cell-assembled BM layer embedded in a collagen I environment. Using this model we demonstrate that while the BM layer fully prevents dissemination of non-malignant cells, cancer cells are capable of breaching it and invading into the surrounding collagen, indicating that the developed system recreates a hallmark of invasive disease. We demonstrate that cancer cells exhibiting individual invasion in collagen matrices preferentially adopt a specific mode of collective invasion when transmigrating a cell-assembled BM that is not observed in any other tested fibrillar, non-fibrillar, or composite ECM. Matrix-degrading enzymes are found to be crucial during BM breaching but not during subsequent invasion in the collagen matrix. It is further shown that multicellular transmigration of the BM is less susceptible to pharmacological MMP inhibition than multicellular invasion in composite collagen/basement membrane extract matrices. The newly developed in vitro model of metastasis allows 3D cancer cell invasion to be studied not only as a function of a particular tumor's genetics but also as a function of its heterogeneous environment and the different stages of invasion. As such, this model is a valuable new tool with which to dissect basic mechanisms of invasion and metastasis and develop new therapeutic approaches in a physiologically relevant, yet inexpensive and highly tunable, in vitro setting.}, } @article {pmid27880868, year = {2017}, author = {Gaiti, F and Calcino, AD and Tanurdžić, M and Degnan, BM}, title = {Origin and evolution of the metazoan non-coding regulatory genome.}, journal = {Developmental biology}, volume = {427}, number = {2}, pages = {193-202}, doi = {10.1016/j.ydbio.2016.11.013}, pmid = {27880868}, issn = {1095-564X}, mesh = {Animals ; *Biological Evolution ; *Gene Expression Regulation ; *Genome ; Humans ; Regulatory Sequences, Nucleic Acid ; }, abstract = {Animals rely on genomic regulatory systems to direct the dynamic spatiotemporal and cell-type specific gene expression that is essential for the development and maintenance of a multicellular lifestyle. Although it is widely appreciated that these systems ultimately evolved from genomic regulatory mechanisms present in single-celled stem metazoans, it remains unclear how this occurred. Here, we focus on the contribution of the non-coding portion of the genome to the evolution of animal gene regulation, specifically on recent insights from non-bilaterian metazoan lineages, and unicellular and colonial holozoan sister taxa. High-throughput next-generation sequencing, largely in bilaterian model species, has led to the discovery of tens of thousands of non-coding RNA genes (ncRNAs), including short, long and circular forms, and uncovered the central roles they play in development. Based on the analysis of non-bilaterian metazoan, unicellular holozoan and fungal genomes, the evolution of some ncRNAs, such as Piwi-interacting RNAs, correlates with the emergence of metazoan multicellularity, while others, including microRNAs, long non-coding RNAs and circular RNAs, appear to be more ancient. Analysis of non-coding regulatory DNA and histone post-translational modifications have revealed that some cis-regulatory mechanisms, such as those associated with proximal promoters, are present in non-animal holozoans, while others appear to be metazoan innovations, most notably distal enhancers. In contrast, the cohesin-CTCF system for regulating higher-order chromatin structure and enhancer-promoter long-range interactions appears to be restricted to bilaterians. Taken together, most bilaterian non-coding regulatory mechanisms appear to have originated before the divergence of crown metazoans. However, differential expansion of non-coding RNA and cis-regulatory DNA repertoires in bilaterians may account for their increased regulatory and morphological complexity relative to non-bilaterians.}, } @article {pmid27876853, year = {2016}, author = {Rodriguez-Pascual, F and Slatter, DA}, title = {Collagen cross-linking: insights on the evolution of metazoan extracellular matrix.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {37374}, pmid = {27876853}, issn = {2045-2322}, mesh = {Amino Acid Sequence ; Animals ; Collagen/classification/genetics/*metabolism ; Evolution, Molecular ; Extracellular Matrix/*metabolism ; Fibrillar Collagens/chemistry/genetics/*metabolism ; Humans ; Invertebrates/genetics/metabolism ; Models, Molecular ; Phylogeny ; Protein Structure, Secondary ; Protein-Lysine 6-Oxidase/*metabolism ; Sequence Homology, Amino Acid ; Vertebrates/genetics/metabolism ; }, abstract = {Collagens constitute a large family of extracellular matrix (ECM) proteins that play a fundamental role in supporting the structure of various tissues in multicellular animals. The mechanical strength of fibrillar collagens is highly dependent on the formation of covalent cross-links between individual fibrils, a process initiated by the enzymatic action of members of the lysyl oxidase (LOX) family. Fibrillar collagens are present in a wide variety of animals, therefore often being associated with metazoan evolution, where the emergence of an ancestral collagen chain has been proposed to lead to the formation of different clades. While LOX-generated collagen cross-linking metabolites have been detected in different metazoan families, there is limited information about when and how collagen acquired this particular modification. By analyzing telopeptide and helical sequences, we identified highly conserved, potential cross-linking sites throughout the metazoan tree of life. Based on this analysis, we propose that they have importantly contributed to the formation and further expansion of fibrillar collagens.}, } @article {pmid27871856, year = {2017}, author = {Pianca, N and Zaglia, T and Mongillo, M}, title = {Will cardiac optogenetics find the way through the obscure angles of heart physiology?.}, journal = {Biochemical and biophysical research communications}, volume = {482}, number = {4}, pages = {515-523}, doi = {10.1016/j.bbrc.2016.11.104}, pmid = {27871856}, issn = {1090-2104}, mesh = {Animals ; Arrhythmias, Cardiac/genetics/pathology/physiopathology/therapy ; Channelrhodopsins ; Equipment Design ; Heart/*physiology/physiopathology ; Humans ; Myocardium/metabolism/pathology ; Optogenetics/instrumentation/*methods ; }, abstract = {Optogenetics is a technique exploded in the last 10 years, which revolutionized several areas of biological research. The brightest side of this technology is the use of light to modulate non-invasively, with high spatial resolution and millisecond time scale, excitable cells genetically modified to express light-sensitive microbial ion channels (opsins). Neuroscience has first benefited from such fascinating strategy, in intact organisms. By shining light to specific neuronal subpopulations, optogenetics allowed unearth the mechanisms involved in cell-to-cell communication within the context of intact organs, such as the brain, formed by complex neuronal circuits. More recently, scientists looked at optogenetics as a tool to answer some of the questions, remained in the dark, of cardiovascular physiology. In this review, we focus on the application of optogenetics in the study of the heart, a complex multicellular organ, homing different populations of excitable cells, spatially and functionally interconnected. Moving from the first proof-of-principle works, published in 2010, to the present time, we discuss the in vitro and in vivo applications of optogenetics for the study of electrophysiology of the different cardiac cell types, and for the dissection of cellular mechanisms underlying arrhythmias. We also present how molecular biology and technology foster the evolution of cardiac optogenetics, with the aim to further our understanding of fundamental questions in cardiac physiology and pathology. Finally, we confer about the therapeutic potential of such biotechnological strategy for the treatment of heart rhythm disturbances (e.g. cardiac pacing, cardioversion).}, } @article {pmid27870211, year = {2016}, author = {Cunningham, JA and Vargas, K and Marone, F and Bengtson, S and Donoghue, PC}, title = {A multicellular organism with embedded cell clusters from the Ediacaran Weng'an biota (Doushantuo Formation, South China).}, journal = {Evolution & development}, volume = {18}, number = {5-6}, pages = {308-316}, pmid = {27870211}, issn = {1525-142X}, mesh = {*Biological Evolution ; China ; Eukaryota/ultrastructure ; Fossils/*anatomy & histology/ultrastructure ; Microscopy, Electron, Scanning ; }, abstract = {Three-dimensional analyses of the early Ediacaran microfossils from the Weng'an biota (Doushantuo Formation) have focused predominantly on multicellular forms that have been interpreted as embryos, and yet they have defied phylogenetic interpretation principally because of absence of evidence from other stages in their life cycle. It is therefore unfortunate that the affinities of the various other Doushantuo microfossils have been neglected. A new conical fossil that is preserved at a cellular level is described here. The fossil contains distinct cell clusters that are characterized and analysed in three dimensions. These clusters are often exposed at the specimen surface, and the fossil preserves many hemispherical craters that are interpreted as positions where clusters have left the organism. The cell clusters may be either reproductive propagules or infesting organisms. Similar clusters are found in a variety of Doushantuo organisms including putative animal embryos and algae.}, } @article {pmid27863931, year = {2016}, author = {Filyk, HA and Osborne, LC}, title = {The Multibiome: The Intestinal Ecosystem's Influence on Immune Homeostasis, Health, and Disease.}, journal = {EBioMedicine}, volume = {13}, number = {}, pages = {46-54}, pmid = {27863931}, issn = {2352-3964}, mesh = {Animals ; Disease Susceptibility ; Ecosystem ; *Gastrointestinal Microbiome ; *Homeostasis ; Host-Parasite Interactions/genetics/immunology ; Host-Pathogen Interactions/genetics/immunology ; Humans ; Immunity, Mucosal ; Immunomodulation ; Intestinal Mucosa/immunology/metabolism/microbiology ; Intestines/*physiology ; }, abstract = {Mammalian evolution has occurred in the presence of mutualistic, commensal, and pathogenic micro- and macro-organisms for millennia. The presence of these organisms during mammalian evolution has allowed for intimate crosstalk between these colonizing species and the host immune system. In this review, we introduce the concept of the 'multibiome' to holistically refer to the biodiverse collection of bacteria, viruses, fungi and multicellular helminthic worms colonizing the mammalian intestine. Furthermore, we discuss new insights into multibiome-host interactions in the context of host-protective immunity and immune-mediated diseases, including inflammatory bowel disease and multiple sclerosis. Finally, we provide reasons to account for the multibiome in experimental design, analysis and in therapeutic applications.}, } @article {pmid27855631, year = {2016}, author = {Singh, R and Schilde, C and Schaap, P}, title = {A core phylogeny of Dictyostelia inferred from genomes representative of the eight major and minor taxonomic divisions of the group.}, journal = {BMC evolutionary biology}, volume = {16}, number = {1}, pages = {251}, pmid = {27855631}, issn = {1471-2148}, support = {BB/K000799/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 100293/Z/12/Z//Wellcome Trust/United Kingdom ; }, mesh = {Base Sequence ; Computational Biology ; Consensus Sequence ; Dictyostelium/*classification/*genetics ; *Genome, Protozoan ; *Phylogeny ; Protozoan Proteins/chemistry/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Dictyostelia are a well-studied group of organisms with colonial multicellularity, which are members of the mostly unicellular Amoebozoa. A phylogeny based on SSU rDNA data subdivided all Dictyostelia into four major groups, but left the position of the root and of six group-intermediate taxa unresolved. Recent phylogenies inferred from 30 or 213 proteins from sequenced genomes, positioned the root between two branches, each containing two major groups, but lacked data to position the group-intermediate taxa. Since the positions of these early diverging taxa are crucial for understanding the evolution of phenotypic complexity in Dictyostelia, we sequenced six representative genomes of early diverging taxa.

RESULTS: We retrieved orthologs of 47 housekeeping proteins with an average size of 890 amino acids from six newly sequenced and eight published genomes of Dictyostelia and unicellular Amoebozoa and inferred phylogenies from single and concatenated protein sequence alignments. Concatenated alignments of all 47 proteins, and four out of five subsets of nine concatenated proteins all produced the same consensus phylogeny with 100% statistical support. Trees inferred from just two out of the 47 proteins, individually reproduced the consensus phylogeny, highlighting that single gene phylogenies will rarely reflect correct species relationships. However, sets of two or three concatenated proteins again reproduced the consensus phylogeny, indicating that a small selection of genes suffices for low cost classification of as yet unincorporated or newly discovered dictyostelid and amoebozoan taxa by gene amplification.

CONCLUSIONS: The multi-locus consensus phylogeny shows that groups 1 and 2 are sister clades in branch I, with the group-intermediate taxon D. polycarpum positioned as outgroup to group 2. Branch II consists of groups 3 and 4, with the group-intermediate taxon Polysphondylium violaceum positioned as sister to group 4, and the group-intermediate taxon Dictyostelium polycephalum branching at the base of that whole clade. Given the data, the approximately unbiased test rejects all alternative topologies favoured by SSU rDNA and individual proteins with high statistical support. The test also rejects monophyletic origins for the genera Acytostelium, Polysphondylium and Dictyostelium. The current position of Acytostelium ellipticum in the consensus phylogeny indicates that somatic cells were lost twice in Dictyostelia.}, } @article {pmid27853598, year = {2016}, author = {Nee, S}, title = {The evolutionary ecology of molecular replicators.}, journal = {Royal Society open science}, volume = {3}, number = {8}, pages = {160235}, pmid = {27853598}, issn = {2054-5703}, abstract = {By reasonable criteria, life on the Earth consists mainly of molecular replicators. These include viruses, transposons, transpovirons, coviruses and many more, with continuous new discoveries like Sputnik Virophage. Their study is inherently multidisciplinary, spanning microbiology, genetics, immunology and evolutionary theory, and the current view is that taking a unified approach has great power and promise. We support this with a new, unified, model of their evolutionary ecology, using contemporary evolutionary theory coupling the Price equation with game theory, studying the consequences of the molecular replicators' promiscuous use of each others' gene products for their natural history and evolutionary ecology. Even at this simple expository level, we can make a firm prediction of a new class of replicators exploiting viruses such as lentiviruses like SIVs, a family which includes HIV: these have been explicitly stated in the primary literature to be non-existent. Closely connected to this departure is the view that multicellular organism immunology is more about the management of chronic infections rather than the elimination of acute ones and new understandings emerging are changing our view of the kind of theatre we ourselves provide for the evolutionary play of molecular replicators. This study adds molecular replicators to bacteria in the emerging field of sociomicrobiology.}, } @article {pmid27845495, year = {2016}, author = {Romero, D}, title = {Unicellular but not asocial. Life in community of a bacterium.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {19}, number = {2}, pages = {81-90}, doi = {10.2436/20.1501.01.266}, pmid = {27845495}, issn = {1139-6709}, mesh = {Bacillus/physiology ; Bacteria/*cytology ; Biological Evolution ; *Microbial Consortia ; }, abstract = {All living organisms have acquired the outstanding ability to overcome the limitations imposed by changeable environments through the gain of genetic traits over years of evolution and the tendency of individuals to associate in communities. The complementation of a singular weakness, the deployment of reinforcement for the good of the community, the better use of resources, or effective defense against external aggression are advantages gained by this communal behavior. Communication has been the cohesive element prompting the global responses that promote efficiency in two features of any community: specialization in differentiated labor and the spatio-temporal organization of the environment. These principles illustrate that what we call human ecology also applies to the cellular world and is exemplified in eukaryotic organisms, where sophisticated cell-to-cell communication networks coordinate cell differentiation and the specialization of multiple tissues consisting of numerous cells embedded in a multifunctional extracellular matrix. This sophisticated molecular machinery appears, however, to be invented by the "simple" but still fascinating bacteria. What I will try to expand in the following sections are notions of how "single prokaryotic cells" organize a multicellular community. [Int Microbiol 19(2):81-90 (2016)].}, } @article {pmid27829356, year = {2016}, author = {Yamashita, S and Arakaki, Y and Kawai-Toyooka, H and Noga, A and Hirono, M and Nozaki, H}, title = {Alternative evolution of a spheroidal colony in volvocine algae: developmental analysis of embryogenesis in Astrephomene (Volvocales, Chlorophyta).}, journal = {BMC evolutionary biology}, volume = {16}, number = {1}, pages = {243}, pmid = {27829356}, issn = {1471-2148}, mesh = {Basal Bodies/metabolism ; *Biological Evolution ; Cell Division ; Cell Lineage ; Cell Nucleus/metabolism ; Chlorophyta/*embryology/*genetics ; Fluorescent Antibody Technique, Indirect ; Phylogeny ; Protoplasts/metabolism ; Time-Lapse Imaging ; }, abstract = {BACKGROUND: Volvocine algae, which range from the unicellular Chlamydomonas to the multicellular Volvox with a germ-soma division of labor, are a model for the evolution of multicellularity. Within this group, the spheroidal colony might have evolved in two independent lineages: Volvocaceae and the goniacean Astrephomene. Astrephomene produces spheroidal colonies with posterior somatic cells. The feature that distinguishes Astrephomene from the volvocacean algae is lack of inversion during embryogenesis; the volvocacean embryo undergoes inversion after successive divisions to orient flagella toward the outside. The mechanisms of inversion at the molecular and cellular levels in volvocacean algae have been assessed in detail, particularly in Volvox carteri. However, embryogenesis in Astrephomene has not been subjected to such investigations.

RESULTS: This study relied on light microscopy time-lapse imaging using an actively growing culture of a newly established strain to conduct a developmental analysis of Astrephomene as well as to perform a comparison with the similar spheroidal volvocacean Eudorina. During the successive divisions involved in Astrephomene embryogenesis, gradual rotation of daughter protoplasts resulted in movement of their apical portions toward the embryonic posterior, forming a convex-to-spheroidal cell sheet with the apical ends of protoplasts on the outside. Differentiation of the posterior somatic cells from the embryo periphery was traced based on cell lineages during embryogenesis. In contrast, in Eudorina, the rotation of daughter protoplasts did not occur during successive cell divisions; however, inversion occurred after such divisions, and a spheroidal embryo was formed. Indirect immunofluorescence microscopy of basal bodies and nuclei verified this difference between Astrephomene and Eudorina in the movement of embryonic protoplasts.

CONCLUSIONS: These results suggest different tactics for spheroidal colony formation between the two lineages: rotation of daughter protoplasts during successive cell divisions in Astrephomene, and inversion after cell divisions in Eudorina. This study will facilitate further research into the molecular and genetic mechanisms of the parallel evolution of the spheroidal colony in volvocine algae.}, } @article {pmid27818507, year = {2016}, author = {Arendt, D and Musser, JM and Baker, CVH and Bergman, A and Cepko, C and Erwin, DH and Pavlicev, M and Schlosser, G and Widder, S and Laubichler, MD and Wagner, GP}, title = {The origin and evolution of cell types.}, journal = {Nature reviews. Genetics}, volume = {17}, number = {12}, pages = {744-757}, pmid = {27818507}, issn = {1471-0064}, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation ; *Cell Lineage ; Cells/classification/*cytology ; *Gene Regulatory Networks ; Humans ; Phylogeny ; }, abstract = {Cell types are the basic building blocks of multicellular organisms and are extensively diversified in animals. Despite recent advances in characterizing cell types, classification schemes remain ambiguous. We propose an evolutionary definition of a cell type that allows cell types to be delineated and compared within and between species. Key to cell type identity are evolutionary changes in the 'core regulatory complex' (CoRC) of transcription factors, that make emergent sister cell types distinct, enable their independent evolution and regulate cell type-specific traits termed apomeres. We discuss the distinction between developmental and evolutionary lineages, and present a roadmap for future research.}, } @article {pmid27818249, year = {2017}, author = {Currais, A}, title = {The origin of life at the origin of ageing?.}, journal = {Ageing research reviews}, volume = {35}, number = {}, pages = {297-300}, doi = {10.1016/j.arr.2016.10.007}, pmid = {27818249}, issn = {1872-9649}, mesh = {Aging/*physiology ; Animals ; Cell Survival/physiology ; Humans ; *Origin of Life ; }, abstract = {At first glance, the ageing of unicellular organisms would appear to be different from the ageing of complex, multicellular organisms. In an attempt to describe the nature of ageing in diverse organisms, the intimate links between the origins of life and ageing are examined. Departing from Leslie Orgel's initial ideas on why organisms age, it is then discussed how the potentially detrimental events characteristic of ageing are continuous, cell-autonomous and universal to all organisms. The manifestation of these alterations relies on the balance between their production and cellular renewal. Renewal is achieved not only by repair and maintenance mechanisms but, importantly, by the process of cell division such that every time cells divide ageing-associated effects are diluted.}, } @article {pmid27816674, year = {2017}, author = {Shelton, DE and Leslie, MP and Michod, RE}, title = {Models of cell division initiation in Chlamydomonas: A challenge to the consensus view.}, journal = {Journal of theoretical biology}, volume = {412}, number = {}, pages = {186-197}, doi = {10.1016/j.jtbi.2016.10.018}, pmid = {27816674}, issn = {1095-8541}, mesh = {Cell Division/*physiology ; Chlamydomonas reinhardtii/*physiology ; *Models, Biological ; }, abstract = {We develop and compare two models for division initiation in cells of the unicellular green alga Chlamydomonas reinhardtii, a topic that has remained controversial in spite of years of empirical work. Achieving a better understanding of C. reinhardtii cell cycle regulation is important because this species is used in studies of fundamental eukaryotic cell features and in studies of the evolution of multicellularity. C. reinhardtii proliferates asexually by multiple fission, interspersing rapid rounds of symmetric division with prolonged periods of growth. Our Model 1 reflects major elements of the current consensus view on C. reinhardtii division initiation, with cells first growing to a specific size, then waiting for a particular time prior to division initiation. In Model 2, our proposed alternative, growing cells divide when they have reached a growth-rate-dependent target size. The two models imply a number of different empirical patterns. We highlight these differences alongside published data, which currently fall short of unequivocally distinguishing these differences in predicted cell behavior. Nevertheless, several lines of evidence are suggestive of more Model 2-like behavior than Model 1-like behavior. Our specification of these models adds rigor to issues that have too often been worked out in relation to loose, verbal models and is directly relevant to future development of informative experiments.}, } @article {pmid27815194, year = {2017}, author = {Fletcher, E and Feizi, A and Bisschops, MMM and Hallström, BM and Khoomrung, S and Siewers, V and Nielsen, J}, title = {Evolutionary engineering reveals divergent paths when yeast is adapted to different acidic environments.}, journal = {Metabolic engineering}, volume = {39}, number = {}, pages = {19-28}, doi = {10.1016/j.ymben.2016.10.010}, pmid = {27815194}, issn = {1096-7184}, mesh = {Acids/*chemistry ; Adaptation, Physiological/*genetics ; Directed Molecular Evolution/*methods ; Gene Expression Regulation, Fungal/genetics ; Genetic Enhancement/methods ; *Hydrogen-Ion Concentration ; Saccharomyces cerevisiae/*chemistry/*genetics ; Saccharomyces cerevisiae Proteins/genetics ; Stress, Physiological/*genetics ; }, abstract = {Tolerance of yeast to acid stress is important for many industrial processes including organic acid production. Therefore, elucidating the molecular basis of long term adaptation to acidic environments will be beneficial for engineering production strains to thrive under such harsh conditions. Previous studies using gene expression analysis have suggested that both organic and inorganic acids display similar responses during short term exposure to acidic conditions. However, biological mechanisms that will lead to long term adaptation of yeast to acidic conditions remains unknown and whether these mechanisms will be similar for tolerance to both organic and inorganic acids is yet to be explored. We therefore evolved Saccharomyces cerevisiae to acquire tolerance to HCl (inorganic acid) and to 0.3M L-lactic acid (organic acid) at pH 2.8 and then isolated several low pH tolerant strains. Whole genome sequencing and RNA-seq analysis of the evolved strains revealed different sets of genome alterations suggesting a divergence in adaptation to these two acids. An altered sterol composition and impaired iron uptake contributed to HCl tolerance whereas the formation of a multicellular morphology and rapid lactate degradation was crucial for tolerance to high concentrations of lactic acid. Our findings highlight the contribution of both the selection pressure and nature of the acid as a driver for directing the evolutionary path towards tolerance to low pH. The choice of carbon source was also an important factor in the evolutionary process since cells evolved on two different carbon sources (raffinose and glucose) generated a different set of mutations in response to the presence of lactic acid. Therefore, different strategies are required for a rational design of low pH tolerant strains depending on the acid of interest.}, } @article {pmid27814692, year = {2016}, author = {Schilde, C and Lawal, HM and Noegel, AA and Eichinger, L and Schaap, P and Glöckner, G}, title = {A set of genes conserved in sequence and expression traces back the establishment of multicellularity in social amoebae.}, journal = {BMC genomics}, volume = {17}, number = {1}, pages = {871}, pmid = {27814692}, issn = {1471-2164}, mesh = {Amoeba/classification/*genetics ; Conserved Sequence ; *Evolution, Molecular ; *Gene Expression ; Gene Expression Profiling ; Gene Knockout Techniques ; Gene Ontology ; Genome ; Mutation ; Phylogeny ; }, abstract = {BACKGROUND: The developmental cycle of Dictyostelid amoebae represents an early form of multicellularity with cell type differentiation. Mutant studies in the model Dictyostelium discoideum revealed that its developmental program integrates the actions of genes involved in signal transduction, adhesion, motility, autophagy and cell wall and matrix biosynthesis. However, due to functional redundancy and fail safe options not required in the laboratory, this single organism approach cannot capture all essential genes. To understand how multicellular organisms evolved, it is essential to recognize both the conserved core features of their developmental programs and the gene modifications that instigated phenotypic innovation. For complex organisms, such as animals, this is not within easy reach, but it is feasible for less complex forms, such as the Dictyostelid social amoebas.

RESULTS: We compared global profiles of gene expression during the development of four social amoebae species that represent 600 mya of Dictyostelia evolution, and identified orthologous conserved genes with similar developmental up-regulation of expression using three different methods. For validation, we disrupted five genes of this core set and examined the phenotypic consequences.

CONCLUSION: At least 71 of the developmentally regulated genes that were identified with all methods were likely to be already present in the last ancestor of all Dictyostelia. The lack of phenotypic changes in null mutants indicates that even highly conserved genes either participate in functionally redundant pathways or are necessary for developmental progression under adverse, non-standard laboratory conditions. Both mechanisms provide robustness to the developmental program, but impose a limit on the information that can be obtained from deleting single genes.}, } @article {pmid27809783, year = {2016}, author = {Pauli, T and Vedder, L and Dowling, D and Petersen, M and Meusemann, K and Donath, A and Peters, RS and Podsiadlowski, L and Mayer, C and Liu, S and Zhou, X and Heger, P and Wiehe, T and Hering, L and Mayer, G and Misof, B and Niehuis, O}, title = {Transcriptomic data from panarthropods shed new light on the evolution of insulator binding proteins in insects : Insect insulator proteins.}, journal = {BMC genomics}, volume = {17}, number = {1}, pages = {861}, pmid = {27809783}, issn = {1471-2164}, mesh = {Animals ; Arthropods/*genetics ; DNA-Binding Proteins/*genetics ; Drosophila melanogaster/genetics ; Enhancer Elements, Genetic ; *Evolution, Molecular ; Gene Expression Profiling ; *Insulator Elements ; Phylogeny ; *Transcriptome ; }, abstract = {BACKGROUND: Body plan development in multi-cellular organisms is largely determined by homeotic genes. Expression of homeotic genes, in turn, is partially regulated by insulator binding proteins (IBPs). While only a few enhancer blocking IBPs have been identified in vertebrates, the common fruit fly Drosophila melanogaster harbors at least twelve different enhancer blocking IBPs. We screened recently compiled insect transcriptomes from the 1KITE project and genomic and transcriptomic data from public databases, aiming to trace the origin of IBPs in insects and other arthropods.

RESULTS: Our study shows that the last common ancestor of insects (Hexapoda) already possessed a substantial number of IBPs. Specifically, of the known twelve insect IBPs, at least three (i.e., CP190, Su(Hw), and CTCF) already existed prior to the evolution of insects. Furthermore we found GAF orthologs in early branching insect orders, including Zygentoma (silverfish and firebrats) and Diplura (two-pronged bristletails). Mod(mdg4) is most likely a derived feature of Neoptera, while Pita is likely an evolutionary novelty of holometabolous insects. Zw5 appears to be restricted to schizophoran flies, whereas BEAF-32, ZIPIC and the Elba complex, are probably unique to the genus Drosophila. Selection models indicate that insect IBPs evolved under neutral or purifying selection.

CONCLUSIONS: Our results suggest that a substantial number of IBPs either pre-date the evolution of insects or evolved early during insect evolution. This suggests an evolutionary history of insulator binding proteins in insects different to that previously thought. Moreover, our study demonstrates the versatility of the 1KITE transcriptomic data for comparative analyses in insects and other arthropods.}, } @article {pmid27809776, year = {2016}, author = {Liu, Z and Ji, Z and Wang, G and Chao, T and Hou, L and Wang, J}, title = {Genome-wide analysis reveals signatures of selection for important traits in domestic sheep from different ecoregions.}, journal = {BMC genomics}, volume = {17}, number = {1}, pages = {863}, pmid = {27809776}, issn = {1471-2164}, mesh = {Animals ; Breeding ; Evolution, Molecular ; Gene Ontology ; Genetics, Population ; *Genome ; *Genome-Wide Association Study ; *Genomics/methods ; High-Throughput Nucleotide Sequencing ; Mutation ; Phenotype ; Polymorphism, Single Nucleotide ; *Quantitative Trait, Heritable ; Reproduction/genetics ; *Selection, Genetic ; Sheep, Domestic/*genetics ; }, abstract = {BACKGROUND: Throughout a long period of adaptation and selection, sheep have thrived in a diverse range of ecological environments. Mongolian sheep is the common ancestor of the Chinese short fat-tailed sheep. Migration to different ecoregions leads to changes in selection pressures and results in microevolution. Mongolian sheep and its subspecies differ in a number of important traits, especially reproductive traits. Genome-wide intraspecific variation is required to dissect the genetic basis of these traits.

RESULTS: This research resequenced 3 short fat-tailed sheep breeds with a 43.2-fold coverage of the sheep genome. We report more than 17 million single nucleotide polymorphisms and 2.9 million indels and identify 143 genomic regions with reduced pooled heterozygosity or increased genetic distance to each other breed that represent likely targets for selection during the migration. These regions harbor genes related to developmental processes, cellular processes, multicellular organismal processes, biological regulation, metabolic processes, reproduction, localization, growth and various components of the stress responses. Furthermore, we examined the haplotype diversity of 3 genomic regions involved in reproduction and found significant differences in TSHR and PRL gene regions among 8 sheep breeds.

CONCLUSIONS: Our results provide useful genomic information for identifying genes or causal mutations associated with important economic traits in sheep and for understanding the genetic basis of adaptation to different ecological environments.}, } @article {pmid27807261, year = {2016}, author = {Regenberg, B and Hanghøj, KE and Andersen, KS and Boomsma, JJ}, title = {Clonal yeast biofilms can reap competitive advantages through cell differentiation without being obligatorily multicellular.}, journal = {Proceedings. Biological sciences}, volume = {283}, number = {1842}, pages = {}, pmid = {27807261}, issn = {1471-2954}, mesh = {*Biofilms ; *Cell Differentiation ; Membrane Glycoproteins/*physiology ; Saccharomyces cerevisiae/*cytology/growth & development ; Saccharomyces cerevisiae Proteins/*physiology ; }, abstract = {How differentiation between cell types evolved is a fundamental question in biology, but few studies have explored single-gene phenotypes that mediate first steps towards division of labour with selective advantage for groups of cells. Here, we show that differential expression of the FLO11 gene produces stable fractions of Flo11[+] and Flo11[-] cells in clonal Saccharomyces cerevisiae biofilm colonies on medium with intermediate viscosity. Differentiated Flo11[+/-] colonies, consisting of adhesive and non-adhesive cells, obtain a fourfold growth advantage over undifferentiated colonies by overgrowing glucose resources before depleting them, rather than depleting them while they grow as undifferentiated Flo11[-] colonies do. Flo11[+/-] colonies maintain their structure and differentiated state by switching non-adhesive cells to adhesive cells with predictable probability. Mixtures of Flo11[+] and Flo11[-] cells from mutant strains that are unable to use this epigenetic switch mechanism produced neither integrated colonies nor growth advantages, so the condition-dependent selective advantages of differentiated FLO11 expression can only be reaped by clone-mate cells. Our results show that selection for cell differentiation in clonal eukaryotes can evolve before the establishment of obligate undifferentiated multicellularity, and without necessarily leading to more advanced organizational complexity.}, } @article {pmid27806710, year = {2016}, author = {Dueck, A and Evers, M and Henz, SR and Unger, K and Eichner, N and Merkl, R and Berezikov, E and Engelmann, JC and Weigel, D and Wenzl, S and Meister, G}, title = {Gene silencing pathways found in the green alga Volvox carteri reveal insights into evolution and origins of small RNA systems in plants.}, journal = {BMC genomics}, volume = {17}, number = {1}, pages = {853}, pmid = {27806710}, issn = {1471-2164}, mesh = {Argonaute Proteins/metabolism ; Base Sequence ; Binding Sites ; Computational Biology/methods ; DNA Transposable Elements ; *Evolution, Molecular ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; *Gene Silencing ; MicroRNAs/genetics ; Molecular Sequence Annotation ; Nucleotide Motifs ; Protein Binding ; RNA, Small Untranslated/*genetics ; Reproducibility of Results ; Transcriptome ; Volvox/*genetics ; }, abstract = {BACKGROUND: Volvox carteri (V. carteri) is a multicellular green alga used as model system for the evolution of multicellularity. So far, the contribution of small RNA pathways to these phenomena is not understood. Thus, we have sequenced V. carteri Argonaute 3 (VcAGO3)-associated small RNAs from different developmental stages.

RESULTS: Using this functional approach, we define the Volvox microRNA (miRNA) repertoire and show that miRNAs are not conserved in the closely related unicellular alga Chlamydomonas reinhardtii. Furthermore, we find that miRNAs are differentially expressed during different life stages of V. carteri. In addition to miRNAs, transposon-associated small RNAs or phased siRNA loci, which are common in higher land plants, are highly abundant in Volvox as well. Transposons not only give rise to miRNAs and other small RNAs, they are also targets of small RNAs.

CONCLUSION: Our analyses reveal a surprisingly complex small RNA network in Volvox as elaborate as in higher land plants. At least the identified VcAGO3-associated miRNAs are not conserved in C. reinhardtii suggesting fast evolution of small RNA systems. Thus, distinct small RNAs may contribute to multicellularity and also division of labor in reproductive and somatic cells.}, } @article {pmid27796199, year = {2016}, author = {Trecartin, A and Danopoulos, S and Spurrier, R and Knaneh-Monem, H and Hiatt, M and Driscoll, B and Hochstim, C and Al-Alam, D and Grikscheit, TC}, title = {Establishing Proximal and Distal Regional Identities in Murine and Human Tissue-Engineered Lung and Trachea.}, journal = {Tissue engineering. Part C, Methods}, volume = {22}, number = {11}, pages = {1049-1057}, pmid = {27796199}, issn = {1937-3392}, mesh = {Animals ; *Cell Lineage ; *Cell Proliferation ; Cells, Cultured ; Humans ; Lung/*cytology/physiology ; Lung Transplantation ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; Tissue Engineering/*methods ; Trachea/cytology/*metabolism ; *Wound Healing ; }, abstract = {The cellular and molecular mechanisms that underpin regeneration of the human lung are unknown, and the study of lung repair has been impeded by the necessity for reductionist models that may exclude key components. We hypothesized that multicellular epithelial and mesenchymal cell clusters or lung organoid units (LuOU) could be transplanted to recapitulate proximal and distal cellular structures of the native lung and airways. Transplantation of LuOU resulted in the growth of tissue-engineered lung (TELu) that contained the necessary cell types consistent with native adult lung tissue and demonstrated proliferative cells at 2 and 4 weeks. This technique recapitulated important elements of both mouse and human lungs featuring key components of both the proximal and distal lung regions. When LuOU were generated from whole lung, TELu contained key epithelial and mesenchymal cell types, and the origin of the cells was traced from both Actin[GFP] and SPC[GFP] donors to indicate that the cells in TELu were derived from the transplanted LuOU. Alveolar epithelial type 2 cells (AEC2s), club cells, ciliated cells marked by beta-tubulin IV, alveolar epithelial type I cells, Sox-2-positive proximal airway progenitors, p63-positive basal cells, and CGRP-positive pulmonary neuroendocrine cells were identified in the TELu. The mesenchymal components of peribronchial smooth muscle and nerve were identified with a CD31-positive donor endothelial cell contribution to TELu vasculature. TELu successfully grew from postnatal tissues from whole murine and human lung, distal murine lung, as well as murine and human trachea. These data support a model of postnatal lung regeneration containing the diverse cell types present in the entirety of the respiratory tract.}, } @article {pmid27790999, year = {2016}, author = {Chen, X and Köllner, TG and Jia, Q and Norris, A and Santhanam, B and Rabe, P and Dickschat, JS and Shaulsky, G and Gershenzon, J and Chen, F}, title = {Terpene synthase genes in eukaryotes beyond plants and fungi: Occurrence in social amoebae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {113}, number = {43}, pages = {12132-12137}, pmid = {27790999}, issn = {1091-6490}, support = {P01 HD039691/HD/NICHD NIH HHS/United States ; R35 GM118016/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; Alkyl and Aryl Transferases/classification/*genetics/metabolism ; Biological Evolution ; Cloning, Molecular ; Dictyostelium/classification/enzymology/*genetics ; Escherichia coli/genetics/metabolism ; Gene Expression ; Gene Expression Regulation, Developmental ; *Genome, Protozoan ; Isoenzymes/classification/genetics/metabolism ; Multigene Family ; *Phylogeny ; Protozoan Proteins/classification/*genetics/metabolism ; Recombinant Proteins/genetics/metabolism ; Terpenes/*metabolism ; Volatilization ; }, abstract = {Terpenes are structurally diverse natural products involved in many ecological interactions. The pivotal enzymes for terpene biosynthesis, terpene synthases (TPSs), had been described only in plants and fungi in the eukaryotic domain. In this report, we systematically analyzed the genome sequences of a broad range of nonplant/nonfungus eukaryotes and identified putative TPS genes in six species of amoebae, five of which are multicellular social amoebae from the order of Dictyosteliida. A phylogenetic analysis revealed that amoebal TPSs are evolutionarily more closely related to fungal TPSs than to bacterial TPSs. The social amoeba Dictyostelium discoideum was selected for functional study of the identified TPSs. D. discoideum grows as a unicellular organism when food is abundant and switches from vegetative growth to multicellular development upon starvation. We found that expression of most D. discoideum TPS genes was induced during development. Upon heterologous expression, all nine TPSs from D. discoideum showed sesquiterpene synthase activities. Some also exhibited monoterpene and/or diterpene synthase activities. Direct measurement of volatile terpenes in cultures of D. discoideum revealed essentially no emission at an early stage of development. In contrast, a bouquet of terpenes, dominated by sesquiterpenes including β-barbatene and (E,E)-α-farnesene, was detected at the middle and late stages of development, suggesting a development-specific function of volatile terpenes in D. discoideum. The patchy distribution of TPS genes in the eukaryotic domain and the evidence for TPS function in D. discoideum indicate that the TPS genes mediate lineage-specific adaptations.}, } @article {pmid27782327, year = {2016}, author = {Elvington, M and Liszewski, MK and Atkinson, JP}, title = {Evolution of the complement system: from defense of the single cell to guardian of the intravascular space.}, journal = {Immunological reviews}, volume = {274}, number = {1}, pages = {9-15}, pmid = {27782327}, issn = {1600-065X}, support = {T32 AR007279/AR/NIAMS NIH HHS/United States ; R01 GM099111/GM/NIGMS NIH HHS/United States ; P30 AR048335/AR/NIAMS NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; R01 AI041592/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Blood Vessels/*physiology ; Cell Membrane/metabolism ; Complement Activation ; Complement C3/*immunology ; Extracellular Space ; Humans ; Immunity ; Inflammation/*immunology ; Intracellular Space ; Liver/*physiology ; Models, Immunological ; }, abstract = {The complement system is an evolutionarily ancient component of immunity that revolves around the central component C3. With the recent description of intracellular C3 stores in many types of human cells, our view of the complement system has expanded. In this article, we hypothesize that a primitive version of C3 comprised the first element of the original complement system and initially functioned intracellularly and on the membrane of single-celled organisms. With increasing specialization and multicellularity, C3 evolved a secretory capacity that allowed it to play a protective role in the interstitial space. Upon development of a pumped circulatory system, C3 was synthesized in large amounts and secreted by the liver to protect the intravascular space. Recent discoveries of intracellular C3 activation, a C3-based recycling pathway and C3 being a driver and programmer of cell metabolism suggest that the complement system utilizes C3 to guard not only extracellular but also the intracellular environment. We predict that the major functions of C3 in all four locations (i.e. intracellular, membrane, interstitium and circulation) are similar: opsonization, membrane perturbation, triggering inflammation, and metabolic reprogramming.}, } @article {pmid27782144, year = {2016}, author = {Balla, KM and Luallen, RJ and Bakowski, MA and Troemel, ER}, title = {Cell-to-cell spread of microsporidia causes Caenorhabditis elegans organs to form syncytia.}, journal = {Nature microbiology}, volume = {1}, number = {11}, pages = {16144}, pmid = {27782144}, issn = {2058-5276}, support = {P40 OD010440/OD/NIH HHS/United States ; R01 GM114139/GM/NIGMS NIH HHS/United States ; T32 GM007240/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/cytology/*microbiology/physiology ; Cytoplasm/microbiology ; Giant Cells/*microbiology ; *Host-Pathogen Interactions ; Intestines/microbiology ; Microsporidia/classification/growth & development/*physiology ; Muscles/microbiology ; Phylogeny ; }, abstract = {The growth of pathogens is dictated by their interactions with the host environment[1]. Obligate intracellular pathogens undergo several cellular decisions as they progress through their life cycles inside host cells[2]. We have studied this process for microsporidian species in the genus Nematocida as they grew and developed inside their co-evolved animal host, Caenorhabditis elegans[3-5]. We found that microsporidia can restructure multicellular host tissues into a single contiguous multinucleate cell. In particular, we found that all three Nematocida species we studied were able to spread across the cells of C. elegans tissues before forming spores, with two species causing syncytial formation in the intestine and one species causing syncytial formation in the muscle. We also found that the decision to switch from replication to differentiation in Nematocida parisii was altered by the density of infection, suggesting that environmental cues influence the dynamics of the pathogen life cycle. These findings show how microsporidia can maximize the use of host space for growth and that environmental cues in the host can regulate a developmental switch in the pathogen.}, } @article {pmid27746046, year = {2016}, author = {Sebé-Pedrós, A and Peña, MI and Capella-Gutiérrez, S and Antó, M and Gabaldón, T and Ruiz-Trillo, I and Sabidó, E}, title = {High-Throughput Proteomics Reveals the Unicellular Roots of Animal Phosphosignaling and Cell Differentiation.}, journal = {Developmental cell}, volume = {39}, number = {2}, pages = {186-197}, doi = {10.1016/j.devcel.2016.09.019}, pmid = {27746046}, issn = {1878-1551}, support = {ERC-2012-CO-616960//European Research Council/International ; }, mesh = {Animals ; *Cell Differentiation ; Eukaryota/cytology/metabolism ; Evolution, Molecular ; Phosphorylation ; Phylogeny ; Protein Kinases/metabolism ; Proteome/metabolism ; Proteomics/*methods ; RNA, Messenger/genetics/metabolism ; *Signal Transduction ; Time Factors ; Transcription Factors/metabolism ; }, abstract = {Cell-specific regulation of protein levels and activity is essential for the distribution of functions among multiple cell types in animals. The finding that many genes involved in these regulatory processes have a premetazoan origin raises the intriguing possibility that the mechanisms required for spatially regulated cell differentiation evolved prior to the appearance of animals. Here, we use high-throughput proteomics in Capsaspora owczarzaki, a close unicellular relative of animals, to characterize the dynamic proteome and phosphoproteome profiles of three temporally distinct cell types in this premetazoan species. We show that life-cycle transitions are linked to extensive proteome and phosphoproteome remodeling and that they affect key genes involved in animal multicellularity, such as transcription factors and tyrosine kinases. The observation of shared features between Capsaspora and metazoans indicates that elaborate and conserved phosphosignaling and proteome regulation supported temporal cell-type differentiation in the unicellular ancestor of animals.}, } @article {pmid27775817, year = {2017}, author = {Goldring, C and Antoine, DJ and Bonner, F and Crozier, J and Denning, C and Fontana, RJ and Hanley, NA and Hay, DC and Ingelman-Sundberg, M and Juhila, S and Kitteringham, N and Silva-Lima, B and Norris, A and Pridgeon, C and Ross, JA and Young, RS and Tagle, D and Tornesi, B and van de Water, B and Weaver, RJ and Zhang, F and Park, BK}, title = {Stem cell-derived models to improve mechanistic understanding and prediction of human drug-induced liver injury.}, journal = {Hepatology (Baltimore, Md.)}, volume = {65}, number = {2}, pages = {710-721}, pmid = {27775817}, issn = {1527-3350}, support = {G0700654/MRC_/Medical Research Council/United Kingdom ; MR/K017047/1/MRC_/Medical Research Council/United Kingdom ; SP/15/9/31605/BHF_/British Heart Foundation/United Kingdom ; PG/09/027/27141/BHF_/British Heart Foundation/United Kingdom ; NC/C013105/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; PG/14/59/31000/BHF_/British Heart Foundation/United Kingdom ; BB/E006159/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; NC/C013202/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; MR/K026666/1/MRC_/Medical Research Council/United Kingdom ; NC/K000225/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; BBS/B/06164/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/L006758/1/MRC_/Medical Research Council/United Kingdom ; MR/L022974/1/MRC_/Medical Research Council/United Kingdom ; G0801098/MRC_/Medical Research Council/United Kingdom ; BB/G021821/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; G113/30/MRC_/Medical Research Council/United Kingdom ; U01 DK065184/DK/NIDDK NIH HHS/United States ; }, mesh = {Cells, Cultured/drug effects ; Chemical and Drug Induced Liver Injury/*diagnosis ; Drug-Related Side Effects and Adverse Reactions/*diagnosis ; Hepatocytes/*drug effects/metabolism ; Humans ; In Vitro Techniques ; Pluripotent Stem Cells/*drug effects/metabolism ; Predictive Value of Tests ; Sensitivity and Specificity ; *Toxicity Tests ; }, abstract = {Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalized toxicology to determine interindividual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury means that no current single-cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human drug-induced liver injury. Nevertheless, a single-cell model of a human hepatocyte which emulates key features of a hepatocyte is likely to be valuable in assessing potential chemical risk; furthermore, understanding how to generate a relevant hepatocyte will also be critical to efforts to build complex multicellular models of the liver. Currently, hepatocyte-like cells differentiated from stem cells still fall short of recapitulating the full mature hepatocellular phenotype. Therefore, we convened a number of experts from the areas of preclinical and clinical hepatotoxicity and safety assessment, from industry, academia, and regulatory bodies, to specifically explore the application of stem cells in hepatotoxicity safety assessment and to make recommendations for the way forward. In this short review, we particularly discuss the importance of benchmarking stem cell-derived hepatocyte-like cells to their terminally differentiated human counterparts using defined phenotyping, to make sure the cells are relevant and comparable between labs, and outline why this process is essential before the cells are introduced into chemical safety assessment. (Hepatology 2017;65:710-721).}, } @article {pmid27751905, year = {2017}, author = {Woyda-Ploszczyca, AM and Jarmuszkiewicz, W}, title = {The conserved regulation of mitochondrial uncoupling proteins: From unicellular eukaryotes to mammals.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1858}, number = {1}, pages = {21-33}, doi = {10.1016/j.bbabio.2016.10.003}, pmid = {27751905}, issn = {0005-2728}, mesh = {Aldehydes/*metabolism ; Animals ; Eukaryota/*metabolism ; Fatty Acids, Nonesterified/*metabolism ; Mammals/*metabolism ; Mitochondrial Uncoupling Proteins/*metabolism ; Purine Nucleotides/*metabolism ; Ubiquinone/*metabolism ; }, abstract = {Uncoupling proteins (UCPs) belong to the mitochondrial anion carrier protein family and mediate regulated proton leak across the inner mitochondrial membrane. Free fatty acids, aldehydes such as hydroxynonenal, and retinoids activate UCPs. However, there are some controversies about the effective action of retinoids and aldehydes alone; thus, only free fatty acids are commonly accepted positive effectors of UCPs. Purine nucleotides such as GTP inhibit UCP-mediated mitochondrial proton leak. In turn, membranous coenzyme Q may play a role as a redox state-dependent metabolic sensor that modulates the complete activation/inhibition of UCPs. Such regulation has been observed for UCPs in microorganisms, plant and animal UCP1 homologues, and UCP1 in mammalian brown adipose tissue. The origin of UCPs is still under debate, but UCP homologues have been identified in all systematic groups of eukaryotes. Despite the differing levels of amino acid/DNA sequence similarities, functional studies in unicellular and multicellular organisms, from amoebae to mammals, suggest that the mechanistic regulation of UCP activity is evolutionarily well conserved. This review focuses on the regulatory feedback loops of UCPs involving free fatty acids, aldehydes, retinoids, purine nucleotides, and coenzyme Q (particularly its reduction level), which may derive from the early stages of evolution as UCP first emerged.}, } @article {pmid27663234, year = {2017}, author = {Kadam, AA and Jubin, T and Mir, HA and Begum, R}, title = {Potential role of Apoptosis Inducing Factor in evolutionarily significant eukaryote, Dictyostelium discoideum survival.}, journal = {Biochimica et biophysica acta. General subjects}, volume = {1861}, number = {1 Pt A}, pages = {2942-2955}, doi = {10.1016/j.bbagen.2016.09.021}, pmid = {27663234}, issn = {0304-4165}, mesh = {Adenosine Triphosphate/metabolism ; Annexin A5/metabolism ; Apoptosis Inducing Factor/*metabolism ; *Biological Evolution ; Calcium/metabolism ; Cell Cycle/drug effects ; Cell Death/drug effects ; Cell Shape/drug effects ; Cytosol/drug effects/metabolism ; Dictyostelium/*cytology/growth & development/*metabolism/ultrastructure ; Down-Regulation/drug effects ; Flow Cytometry ; Fluorescein-5-isothiocyanate/metabolism ; Fluorometry ; Glucose/pharmacology ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/drug effects/metabolism ; Models, Biological ; NAD/metabolism ; Oxidative Stress/drug effects ; Propidium/metabolism ; Protein Transport/drug effects ; RNA, Antisense/metabolism ; Reactive Oxygen Species/metabolism ; Staining and Labeling ; }, abstract = {Apoptosis Inducing Factor (AIF), a phylogenetically conserved mitochondrial inter-membrane space flavoprotein has an important role in caspase independent cell death. Nevertheless, AIF is also essential for cell survival. It is required for mitochondrial organization and energy metabolism. Upon apoptotic stimulation, AIF induces DNA fragmentation after its mitochondrio-nuclear translocation. Although it executes critical cellular functions in a coordinated manner, the exact mechanism still remains obscure. The present study aims to understand AIF's role in cell survival, growth and development by its down-regulation in an interesting unicellular eukaryote, D. discoideum which exhibits multicellularity upon starvation. Constitutive AIF down-regulated (dR) cells exhibited slower growth and delayed developmental morphogenesis. Also, constitutive AIF dR cells manifested high intracellular ROS, oxidative DNA damage and calcium levels with lower ATP content. Interestingly, constitutive AIF dR cells showed amelioration in cell growth upon antioxidant treatment, strengthening its role as ROS regulator. Under oxidative stress, AIF dR cells showed early mitochondrial membrane depolarization followed by AIF translocation from mitochondria to nucleus and exhibited necrotic cell death as compared to paraptoptic cell death of control cells. Thus, the results of this study provide an exemplar where AIF is involved in growth and development by regulating ROS levels and maintaining mitochondrial function in D. discoideum, an evolutionarily significant model organism exhibiting caspase independent apoptosis.}, } @article {pmid27718356, year = {2016}, author = {Carmell, MA and Dokshin, GA and Skaletsky, H and Hu, YC and van Wolfswinkel, JC and Igarashi, KJ and Bellott, DW and Nefedov, M and Reddien, PW and Enders, GC and Uversky, VN and Mello, CC and Page, DC}, title = {A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes.}, journal = {eLife}, volume = {5}, number = {}, pages = {}, pmid = {27718356}, issn = {2050-084X}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Antigens, Nuclear/*genetics/metabolism ; Caenorhabditis elegans/genetics/growth & development ; Eukaryota/genetics ; *Evolution, Molecular ; Gene Expression Regulation/genetics ; Genome/genetics ; Genomics ; Germ Cells/growth & development/*metabolism ; Meiosis/genetics ; Phylogeny ; Reproduction/*genetics ; }, abstract = {The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya - either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells of diverse multicellular animals. Studies of Gcna-mutant C. elegans and mice indicate that GCNA has functioned in reproduction for at least 600 million years. Homology to IDR-containing proteins implicated in DNA damage repair suggests that GCNA proteins may protect the genomic integrity of cells carrying a heritable genome.}, } @article {pmid27751769, year = {2016}, author = {Gadahi, JA and Ehsan, M and Wang, S and Zhang, Z and Wang, Y and Yan, R and Song, X and Xu, L and Li, X}, title = {Recombinant protein of Haemonchus contortus 14-3-3 isoform 2 (rHcftt-2) decreased the production of IL-4 and suppressed the proliferation of goat PBMCs in vitro.}, journal = {Experimental parasitology}, volume = {171}, number = {}, pages = {57-66}, doi = {10.1016/j.exppara.2016.10.014}, pmid = {27751769}, issn = {1090-2449}, mesh = {Amino Acid Sequence ; Animals ; Antibodies, Helminth/biosynthesis ; Cell Proliferation/drug effects ; Cloning, Molecular ; DNA, Complementary/metabolism ; DNA, Helminth/metabolism ; Dose-Response Relationship, Drug ; Female ; Goats ; Haemonchus/chemistry/genetics/*immunology ; Helminth Proteins/chemistry/*immunology/pharmacology ; Interleukin-4/*immunology/metabolism ; Neutrophils/*immunology/metabolism ; Nitric Oxide/metabolism ; Phylogeny ; Polymerase Chain Reaction ; Protein Isoforms/immunology/pharmacology ; RNA, Helminth/genetics/isolation & purification ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/*immunology/pharmacology ; Sequence Alignment ; }, abstract = {14-3-3 proteins have been found to be an excreted/secreted antigen and assumed to be released into the host-parasite interface and described in several unicellular and multicellular parasites. However, little is known about the immunomodulatory effects of H. controtus 14-3-3 protein on host cell. In present study, 14-3-3 isoform 2 gene, designated as Hcftt-2, was amplified by reverse transcription-polymerase chain reaction (RT-PCR) from the adult H. contortus cDNA and cloned into expression plasmid pET32a (+) and expression of the recombinant protein (rHcftt-2) was induced by IPTG. Binding activity of rHcftt-2 to goat peripheral blood mononuclear cells (PBMCs) was confirmed by immunofluorescence assay (IFA) and modulatory effects on cytokine production, cell proliferation, cell migration and nitric oxide (NO) production were observed by co-incubation of rHcftt-2 with goat PBMCs. Sequence analysis showed that it had significant homology with the known 14-3-3 protein isoform 2. Results of IFA revealed that, the rHcftt-2 was bound to the cell surface. We found that, the productions of IL10, IL-17, IFN-γ and cell migration of PBMCs were increased after the cells were incubated with rHCftt-2. However, the productions of IL-4, NO and cell proliferation of the PBMCs were significantly decreased in dose depended manner. Our results showed that the Hcftt-2 played important suppressive regulatory effects on the goat PBMCs.}, } @article {pmid27738200, year = {2016}, author = {Spatafora, JW and Chang, Y and Benny, GL and Lazarus, K and Smith, ME and Berbee, ML and Bonito, G and Corradi, N and Grigoriev, I and Gryganskyi, A and James, TY and O'Donnell, K and Roberson, RW and Taylor, TN and Uehling, J and Vilgalys, R and White, MM and Stajich, JE}, title = {A phylum-level phylogenetic classification of zygomycete fungi based on genome-scale data.}, journal = {Mycologia}, volume = {108}, number = {5}, pages = {1028-1046}, pmid = {27738200}, issn = {0027-5514}, support = {S10 OD016290/OD/NIH HHS/United States ; }, mesh = {Fungi/*classification/*genetics ; *Genome, Fungal ; *Phylogeny ; }, abstract = {Zygomycete fungi were classified as a single phylum, Zygomycota, based on sexual reproduction by zygospores, frequent asexual reproduction by sporangia, absence of multicellular sporocarps, and production of coenocytic hyphae, all with some exceptions. Molecular phylogenies based on one or a few genes did not support the monophyly of the phylum, however, and the phylum was subsequently abandoned. Here we present phylogenetic analyses of a genome-scale data set for 46 taxa, including 25 zygomycetes and 192 proteins, and we demonstrate that zygomycetes comprise two major clades that form a paraphyletic grade. A formal phylogenetic classification is proposed herein and includes two phyla, six subphyla, four classes and 16 orders. On the basis of these results, the phyla Mucoromycota and Zoopagomycota are circumscribed. Zoopagomycota comprises Entomophtoromycotina, Kickxellomycotina and Zoopagomycotina; it constitutes the earliest diverging lineage of zygomycetes and contains species that are primarily parasites and pathogens of small animals (e.g. amoeba, insects, etc.) and other fungi, i.e. mycoparasites. Mucoromycota comprises Glomeromycotina, Mortierellomycotina, and Mucoromycotina and is sister to Dikarya. It is the more derived clade of zygomycetes and mainly consists of mycorrhizal fungi, root endophytes, and decomposers of plant material. Evolution of trophic modes, morphology, and analysis of genome-scale data are discussed.}, } @article {pmid27737633, year = {2016}, author = {Lumsden, AL and Young, RL and Pezos, N and Keating, DJ}, title = {Huntingtin-associated protein 1: Eutherian adaptation from a TRAK-like protein, conserved gene promoter elements, and localization in the human intestine.}, journal = {BMC evolutionary biology}, volume = {16}, number = {1}, pages = {214}, pmid = {27737633}, issn = {1471-2148}, mesh = {Animals ; Base Sequence ; Binding Sites ; Caenorhabditis elegans/genetics ; Conserved Sequence/*genetics ; Humans ; Intestinal Mucosa/*metabolism ; Mammals/*genetics ; Mitochondria/genetics ; Multigene Family ; Nerve Tissue Proteins/*metabolism ; Nucleotide Motifs/genetics ; Phylogeny ; *Promoter Regions, Genetic ; Protein Binding/genetics ; Protein Domains ; Protein Transport ; Reproducibility of Results ; Sequence Homology, Nucleic Acid ; Serotonin/metabolism ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: Huntingtin-associated Protein 1 (HAP1) is expressed in neurons and endocrine cells, and is critical for postnatal survival in mice. HAP1 shares a conserved "HAP1_N" domain with TRAfficking Kinesin proteins TRAK1 and TRAK2 (vertebrate), Milton (Drosophila) and T27A3.1 (C. elegans). HAP1, TRAK1 and TRAK2 have a degree of common function, particularly regarding intracellular receptor trafficking. However, TRAK1, TRAK2 and Milton (which have a "Milt/TRAK" domain that is absent in human and rodent HAP1) differ in function to HAP1 in that they are mitochondrial transport proteins, while HAP1 has emerging roles in starvation response. We have investigated HAP1 function by examining its evolution, and upstream gene promoter sequences. We performed phylogenetic analyses of the HAP1_N domain family of proteins, incorporating HAP1 orthologues (identified by genomic synteny) from 5 vertebrate classes, and also searched the Dictyostelium proteome for a common ancestor. Computational analyses of mammalian HAP1 gene promoters were performed to identify phylogenetically conserved regulatory motifs.

RESULTS: We found that as recently as marsupials, HAP1 contained a Milt/TRAK domain and was more similar to TRAK1 and TRAK2 than to eutherian HAP1. The Milt/TRAK domain likely arose post multicellularity, as it was absent in the Dictyostelium proteome. It was lost from HAP1 in the eutherian lineage, and also from T27A3.1 in C. elegans. The HAP1 promoter from human, mouse, rat, rabbit, horse, dog, Tasmanian devil and opossum contained common sites for transcription factors involved in cell cycle, growth, differentiation, and stress response. A conserved arrangement of regulatory elements was identified, including sites for caudal-related homeobox transcription factors (CDX1 and CDX2), and myc-associated factor X (MAX) in the region of the TATA box. CDX1 and CDX2 are intestine-enriched factors, prompting investigation of HAP1 protein expression in the human duodenum. HAP1 was localized to singly dispersed mucosal cells, including a subset of serotonin-positive enterochromaffin cells.

CONCLUSION: We have identified eutherian HAP1 as an evolutionarily recent adaptation of a vertebrate TRAK protein-like ancestor, and found conserved CDX1/CDX2 and MAX transcription factor binding sites near the TATA box in mammalian HAP1 gene promoters. We also demonstrated that HAP1 is expressed in endocrine cells of the human gut.}, } @article {pmid27733125, year = {2016}, author = {Höhn, S and Hallmann, A}, title = {Distinct shape-shifting regimes of bowl-shaped cell sheets - embryonic inversion in the multicellular green alga Pleodorina.}, journal = {BMC developmental biology}, volume = {16}, number = {1}, pages = {35}, pmid = {27733125}, issn = {1471-213X}, mesh = {Biological Evolution ; Cell Division ; Chlorophyta/*cytology/*embryology/ultrastructure ; Microscopy, Electron, Transmission ; *Models, Biological ; *Morphogenesis ; Photogrammetry ; Time Factors ; }, abstract = {BACKGROUND: The multicellular volvocine alga Pleodorina is intermediate in organismal complexity between its unicellular relative, Chlamydomonas, and its multicellular relative, Volvox, which shows complete division of labor between different cell types. The volvocine green microalgae form a group of genera closely related to the genus Volvox within the order Volvocales (Chlorophyta). Embryos of multicellular volvocine algae consist of a cellular monolayer that, depending on the species, is either bowl-shaped or comprises a sphere. During embryogenesis, multicellular volvocine embryos turn their cellular monolayer right-side out to expose their flagella. This process is called 'inversion' and serves as simple model for epithelial folding in metazoa. While the development of spherical Volvox embryos has been the subject of detailed studies, the inversion process of bowl-shaped embryos is less well understood. Therefore, it has been unclear how the inversion of a sphere might have evolved from less complicated processes.

RESULTS: In this study we characterized the inversion of initially bowl-shaped embryos of the 64- to 128-celled volvocine species Pleodorina californica. We focused on the movement patterns of the cell sheet, cell shape changes and changes in the localization of cytoplasmic bridges (CBs) connecting the cells. The development of living embryos was recorded using time-lapse light microscopy. Moreover, fixed and sectioned embryos throughout inversion and at successive stages of development were analyzed by light and transmission electron microscopy. We generated three-dimensional models of the identified cell shapes including the localization of CBs.

CONCLUSIONS: In contrast to descriptions concerning volvocine embryos with lower cell numbers, the embryonic cells of P. californica undergo non-simultaneous and non-uniform cell shape changes. In P. californica, cell wedging in combination with a relocation of the CBs to the basal cell tips explains the curling of the cell sheet during inversion. In volvocine genera with lower organismal complexity, the cell shape changes and relocation of CBs are less pronounced in comparison to P. californica, while they are more pronounced in all members of the genus Volvox. This finding supports an increasing significance of the temporal and spatial regulation of cell shape changes and CB relocations with both increasing cell number and organismal complexity during evolution of differentiated multicellularity.}, } @article {pmid27717470, year = {2016}, author = {Devic, M and Roscoe, T}, title = {Seed maturation: Simplification of control networks in plants.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {252}, number = {}, pages = {335-346}, doi = {10.1016/j.plantsci.2016.08.012}, pmid = {27717470}, issn = {1873-2259}, mesh = {Gene Expression Regulation, Plant ; Gene Regulatory Networks ; Multigene Family ; Plant Development/*genetics ; Plant Proteins/genetics/metabolism/physiology ; Seeds/*genetics/growth & development ; Transcription Factors/genetics/metabolism/physiology ; }, abstract = {Networks controlling developmental or metabolic processes in plants are often complex as a consequence of the duplication and specialisation of the regulatory genes as well as the numerous levels of transcriptional and post-transcriptional controls added during evolution. Networks serve to accommodate multicellular complexity and increase robustness to environmental changes. Mathematical simplification by regrouping genes or pathways in a limited number of hubs has facilitated the construction of models for complex traits. In a complementary approach, a biological simplification can be achieved by using genetic modification to understand the core and singular ancestral function of the network, which is likely to be more prevalent within the plant kingdom rather than specific to a species. With this viewpoint, we review examples of simplification successfully undertaken in yeast and other organisms. A strategy of progressive complementation of single, double and triple mutants of seed maturation confirmed the fundamental role of the AFL sub-family of B3 transcription factors as master regulators of seed maturation, illustrating that biological simplification of complex networks could be more widely applied in plants. Defining minimal control networks will facilitate evolutionary comparisons of regulatory processes and the identification of an essential gene set for synthetic biology.}, } @article {pmid27708766, year = {2016}, author = {Fozard, JA and Bennett, MJ and King, JR and Jensen, OE}, title = {Hybrid vertex-midline modelling of elongated plant organs.}, journal = {Interface focus}, volume = {6}, number = {5}, pages = {20160043}, pmid = {27708766}, issn = {2042-8898}, abstract = {We describe a method for the simulation of the growth of elongated plant organs, such as seedling roots. By combining a midline representation of the organ on a tissue scale and a vertex-based representation on the cell scale, we obtain a multiscale method, which is able to both simulate organ growth and incorporate cell-scale processes. Equations for the evolution of the midline are obtained, which depend on the cell-wall properties of individual cells through appropriate averages over the vertex-based representation. The evolution of the organ midline is used to deform the cellular-scale representation. This permits the investigation of the regulation of organ growth through the cell-scale transport of the plant hormone auxin. The utility of this method is demonstrated in simulating the early stages of the response of a root to gravity, using a vertex-based template acquired from confocal imaging. Asymmetries in the concentrations of auxin between the upper and lower sides of the root lead to bending of the root midline, reflecting a gravitropic response.}, } @article {pmid27703714, year = {2016}, author = {Manjarrez-Casas, AM and Bagheri, HC and Dobay, A}, title = {Transition from one- to two-dimensional development facilitates maintenance of multicellularity.}, journal = {Royal Society open science}, volume = {3}, number = {9}, pages = {160554}, pmid = {27703714}, issn = {2054-5703}, abstract = {Filamentous organisms represent an example where incomplete separation after cell division underlies the development of multicellular formations. With a view to understanding the evolution of more complex multicellular structures, we explore the transition of multicellular growth from one to two dimensions. We develop a computational model to simulate multicellular development in populations where cells exhibit density-dependent division and death rates. In both the one- and two-dimensional contexts, multicellular formations go through a developmental cycle of growth and subsequent decay. However, the model shows that a transition to a higher dimension increases the size of multicellular formations and facilitates the maintenance of large cell clusters for significantly longer periods of time. We further show that the turnover rate for cell division and death scales with the number of iterations required to reach the stationary multicellular size at equilibrium. Although size and life cycles of multicellular organisms are affected by other environmental and genetic factors, the model presented here evaluates the extent to which the transition of multicellular growth from one to two dimensions contributes to the maintenance of multicellular structures during development.}, } @article {pmid27697546, year = {2017}, author = {Cai, W and Zhang, K and Li, P and Zhu, L and Xu, J and Yang, B and Hu, X and Lu, Z and Chen, J}, title = {Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative diseases: An aging effect.}, journal = {Ageing research reviews}, volume = {34}, number = {}, pages = {77-87}, pmid = {27697546}, issn = {1872-9649}, support = {R01 NS089534/NS/NINDS NIH HHS/United States ; R01 NS095671/NS/NINDS NIH HHS/United States ; I01 BX002495/BX/BLRD VA/United States ; I01 RX000420/RX/RRD VA/United States ; R01 NS036736/NS/NINDS NIH HHS/United States ; R01 NS045048/NS/NINDS NIH HHS/United States ; }, mesh = {Aging/*physiology ; Blood-Brain Barrier ; *Brain/blood supply/pathology/physiopathology ; Humans ; *Neurodegenerative Diseases/pathology/physiopathology ; Neurovascular Coupling/*physiology ; *Stroke/pathology/physiopathology ; }, abstract = {Current understanding on the mechanisms of brain injury and neurodegeneration highlights an appreciation of multicellular interactions within the neurovascular unit (NVU), which include the evolution of blood-brain barrier (BBB) damage, neuronal cell death or degeneration, glial reaction, and immune cell infiltration. Aging is an important factor that influences the integrity of the NVU. The age-related physiological or pathological changes in the cellular components of the NVU have been shown to increase the vulnerability of the NVU to ischemia/reperfusion injury or neurodegeneration, and to result in deteriorated brain damage. This review describes the impacts of aging on each NVU component and discusses the mechanisms by which aging increases NVU sensitivity to stroke and neurodegenerative diseases. Prophylactic or therapeutic perspectives that may delay or diminish aging and thus prevent the incidence of these neurological disorders will also be reviewed.}, } @article {pmid27693864, year = {2016}, author = {Kuburich, NA and Adhikari, N and Hadwiger, JA}, title = {Acanthamoeba and Dictyostelium Use Different Foraging Strategies.}, journal = {Protist}, volume = {167}, number = {6}, pages = {511-525}, pmid = {27693864}, issn = {1618-0941}, support = {R15 GM097717/GM/NIGMS NIH HHS/United States ; }, mesh = {Acanthamoeba/classification/genetics/*physiology ; *Chemotaxis ; Dictyostelium/classification/genetics/*physiology ; Phylogeny ; Protozoan Proteins/genetics ; Signal Transduction ; }, abstract = {Amoeba often use cell movement as a mechanism to find food, such as bacteria, in their environment. The chemotactic movement of the soil amoeba Dictyostelium to folate or other pterin compounds released by bacteria is a well-documented foraging mechanism. Acanthamoeba can also feed on bacteria but relatively little is known about the mechanism(s) by which this amoeba locates bacteria. Acanthamoeba movement in the presence of folate or bacteria was analyzed in above agar assays and compared to that observed for Dictyostelium. The overall mobility of Acanthamoeba was robust like that of Dictyostelium but Acanthamoeba did not display a chemotactic response to folate. In the presence of bacteria, Acanthamoeba only showed a marginal bias in directed movement whereas Dictyostelium displayed a strong chemotactic response. A comparison of genomes revealed that Acanthamoeba and Dictyostelium share some similarities in G protein signaling components but that specific G proteins used in Dictyostelium chemotactic responses were not present in current Acanthamoeba genome sequence data. The results of this study suggest that Acanthamoeba does not use chemotaxis as the primary mechanism to find bacterial food sources and that the chemotactic responses of Dictyostelium to bacteria may have co-evolved with chemotactic responses that facilitate multicellular development.}, } @article {pmid27686422, year = {2017}, author = {Mills, DB and Canfield, DE}, title = {A trophic framework for animal origins.}, journal = {Geobiology}, volume = {15}, number = {2}, pages = {197-210}, doi = {10.1111/gbi.12216}, pmid = {27686422}, issn = {1472-4669}, mesh = {Animals ; *Biological Evolution ; Feeding Behavior ; *Heterotrophic Processes ; Organic Chemicals/*metabolism ; *Phagocytosis ; }, abstract = {Metazoans emerged in a microbial world and play a unique role in the biosphere as the only complex multicellular eukaryotes capable of phagocytosis. While the bodyplan and feeding mode of the last common metazoan ancestor remain unresolved, the earliest multicellular stem-metazoans likely subsisted on picoplankton (planktonic microbes 0.2-2 μm in diameter) and dissolved organic matter (DOM), similarly to modern sponges. Once multicellular stem-metazoans emerged, they conceivably modulated both the local availability of picoplankton, which they preferentially removed from the water column for feeding, and detrital particles 2-100 μm in diameter, which they expelled and deposited into the benthos as waste products. By influencing the availability of these heterotrophic food sources, the earliest multicellular stem-metazoans would have acted as ecosystem engineers, helping create the ecological conditions under which other metazoans, namely detritivores and non-sponge suspension feeders incapable of subsisting on picoplankton and DOM, could emerge and diversify. This early style of metazoan feeding, specifically the phagocytosis of small eukaryotic prey, could have also encouraged the evolution of larger, even multicellular, eukaryotic forms less prone to metazoan consumption. Therefore, the first multicellular stem-metazoans, through their feeding, arguably helped bridge the strictly microbial food webs of the Proterozoic Eon (2.5-0.541 billion years ago) to the more macroscopic, metazoan-sustaining food webs of the Phanerozoic Eon (0.541-0 billion years ago).}, } @article {pmid27686281, year = {2016}, author = {Wu, CI and Wang, HY and Ling, S and Lu, X}, title = {The Ecology and Evolution of Cancer: The Ultra-Microevolutionary Process.}, journal = {Annual review of genetics}, volume = {50}, number = {}, pages = {347-369}, doi = {10.1146/annurev-genet-112414-054842}, pmid = {27686281}, issn = {1545-2948}, mesh = {Animals ; *Biological Evolution ; Ecology ; Genetic Variation ; Genetics, Population ; Genome, Human ; Genotype ; Humans ; Neoplasms/*etiology/genetics ; Phenotype ; Population Growth ; *Selection, Genetic ; }, abstract = {Although tumorigenesis has been accepted as an evolutionary process (20 , 102), many forces may operate differently in cancers than in organisms, as they evolve at vastly different time scales. Among such forces, natural selection, here defined as differential cellular proliferation among distinct somatic cell genotypes, is particularly interesting because its action might be thwarted in multicellular organisms (20 , 29). In this review, selection is analyzed in two stages of cancer evolution: Stage I is the evolution between tumors and normal tissues, and Stage II is the evolution within tumors. The Cancer Genome Atlas (TCGA) data show a low degree of convergent evolution in Stage I, where genetic changes are not extensively shared among cases. An equally important, albeit much less highlighted, discovery using TCGA data is that there is almost no net selection in cancer evolution. Both positive and negative selection are evident but they neatly cancel each other out, rendering total selection ineffective in the absence of recombination. The efficacy of selection is even lower in Stage II, where neutral (non-Darwinian) evolution is increasingly supported by high-density sampling studies (81 , 123). Because natural selection is not a strong deterministic force, cancers usually evolve divergently even in similar tissue environments.}, } @article {pmid27676437, year = {2016}, author = {Loh, KM and van Amerongen, R and Nusse, R}, title = {Generating Cellular Diversity and Spatial Form: Wnt Signaling and the Evolution of Multicellular Animals.}, journal = {Developmental cell}, volume = {38}, number = {6}, pages = {643-655}, doi = {10.1016/j.devcel.2016.08.011}, pmid = {27676437}, issn = {1878-1551}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Biological Evolution ; Cell Division/genetics ; Cell Lineage/*genetics ; Cell Polarity/genetics ; Embryonic Development/genetics ; Gene Expression Regulation, Developmental/genetics ; *Genetic Variation ; Signal Transduction ; Wnt Proteins/*genetics ; }, abstract = {There were multiple prerequisites to the evolution of multicellular animal life, including the generation of multiple cell fates ("cellular diversity") and their patterned spatial arrangement ("spatial form"). Wnt proteins operate as primordial symmetry-breaking signals. By virtue of their short-range nature and their capacity to activate both lineage-specifying and cell-polarizing intracellular signaling cascades, Wnts can polarize cells at their site of contact, orienting the axis of cell division while simultaneously programming daughter cells to adopt diverging fates in a spatially stereotyped way. By coupling cell fate to position, symmetry-breaking Wnt signals were pivotal in constructing the metazoan body by generating cellular diversity and spatial form.}, } @article {pmid27672092, year = {2016}, author = {Noble, LM and Holland, LM and McLauchlan, AJ and Andrianopoulos, A}, title = {A Plastic Vegetative Growth Threshold Governs Reproductive Capacity in Aspergillus nidulans.}, journal = {Genetics}, volume = {204}, number = {3}, pages = {1161-1175}, pmid = {27672092}, issn = {1943-2631}, mesh = {Aspergillus nidulans/*genetics/growth & development ; *Gene Expression Regulation, Fungal ; Gene-Environment Interaction ; Reproduction, Asexual/*genetics ; ras Proteins/genetics/metabolism ; }, abstract = {Ontogenetic phases separating growth from reproduction are a common feature of cellular life. Long recognized for flowering plants and animals, early literature suggests this life-history component may also be prevalent among multicellular fungi. We establish the basis of developmental competence-the capacity to respond to induction of asexual development-in the filamentous saprotroph Aspergillus nidulans, describing environmental influences, including genotype-by-environment interactions among precocious mutants, gene expression associated with wild type and precocious competence acquisition, and the genetics of competence timing. Environmental effects are consistent with a threshold driven by metabolic rate and organism density, with pH playing a particularly strong role in determining competence timing. Gene expression diverges significantly over the competence window, despite a lack of overt morphological change, with differentiation in key metabolic, signaling, and cell trafficking processes. We identify five genes for which mutant alleles advance competence timing, including the conserved GTPase RasB (AN5832) and ambient pH sensor PalH (AN6886). In all cases examined, inheritance of competence timing is complex and non-Mendelian, with F1 progeny showing highly variable transgressive timing and dominant parental effects with a weak contribution from progeny genotype. Competence provides a new model for nutrient-limited life-cycle phases, and their elaboration from unicellular origins. Further work is required to establish the hormonal and bioenergetic basis of the trait across fungi, and underlying mechanisms of variable inheritance.}, } @article {pmid27663838, year = {2017}, author = {Ageitos, JM and Sánchez-Pérez, A and Calo-Mata, P and Villa, TG}, title = {Antimicrobial peptides (AMPs): Ancient compounds that represent novel weapons in the fight against bacteria.}, journal = {Biochemical pharmacology}, volume = {133}, number = {}, pages = {117-138}, doi = {10.1016/j.bcp.2016.09.018}, pmid = {27663838}, issn = {1873-2968}, mesh = {Amino Acid Sequence ; Animals ; Antimicrobial Cationic Peptides/*chemistry/genetics/*pharmacology ; Biological Products/*chemistry/*pharmacology ; Cell Wall/drug effects/physiology ; Drug Resistance, Multiple, Bacterial/*drug effects/physiology ; Humans ; Methicillin-Resistant Staphylococcus aureus/drug effects/physiology ; Microbial Sensitivity Tests/methods ; Protein Structure, Secondary ; }, abstract = {Antimicrobial peptides (AMPs) are short peptidic molecules produced by most living creatures. They help unicellular organisms to successfully compete for nutrients with other organisms sharing their biological niche, while AMPs form part of the immune system of multicellular creatures. Thus, these molecules represent biological weapons that have evolved over millions of years as a result of an escalating arms race for survival among living organisms. All AMPs share common features, such as a small size, with cationic and hydrophobic sequences within a linear or cyclic structure. AMPs can inhibit or kill bacteria at micromolar concentrations, often by non-specific mechanisms; hence the appearance of resistance to these antimicrobials is rare. Moreover, AMPs can kill antibiotic-resistant bacteria, including insidious microbes such as Acinetobacter baumannii and the methicillin-resistant Staphylococcus aureus. This review gives a detailed insight into a selection of the most prominent and interesting AMPs with antibacterial activity. In the near future AMPs, due to their properties and despite their ancient origin, should represent a novel alternative to antibiotics in the struggle to control pathogenic microorganisms and maintain the current human life expectancy.}, } @article {pmid27637882, year = {2016}, author = {Wong, M and Liang, X and Smart, M and Tang, L and Moore, R and Ingalls, B and Dong, TG}, title = {Microbial herd protection mediated by antagonistic interaction in polymicrobial communities.}, journal = {Applied and environmental microbiology}, volume = {82}, number = {23}, pages = {6881-6888}, pmid = {27637882}, issn = {1098-5336}, abstract = {UNLABELLED: In the host and natural environments, microbes often exist in complex multispecies communities. The molecular mechanisms through which such communities develop and persist - despite significant antagonistic interactions between species - are not well understood. The type VI secretion system (T6SS) is a lethal weapon commonly employed by Gram-negative bacteria to inhibit neighboring species through delivery of toxic effectors. It is well established that intra-species protection is conferred by immunity proteins that neutralize effector toxicities. By contrast, the mechanisms for interspecies protection are not clear. Here we use two T6SS active antagonistic bacteria, Aeromonas hydrophila (AH) and Vibrio cholerae (VC), to demonstrate that interspecies protection is dependent on effectors. AH and VC do not share conserved immunity genes but could equally co-exist in a mixture. However, mutants lacking the T6SS or effectors were effectively eliminated by the other competing wild type. Time-lapse microscopy analyses show that mutually lethal interactions drive the segregation of mixed species into distinct single-species clusters by eliminating interspersed single cells. Cluster formation provides herd protection by abolishing lethal interaction inside each cluster and restricting it to the boundary. Using an agent-based modeling approach, we simulated the antagonistic interactions of two hypothetical species. The resulting simulations recapitulate our experimental observation. These results provide mechanistic insights for the general role of microbial weapons in determining the structures of complex multispecies communities.

IMPORTANCE: Investigating the warfare of microbes allows us to better understand the ecological relationships in complex microbial communities such as the human microbiota. Here we use the T6SS, a deadly bacterial weapon, as a model to demonstrate the importance of lethal interactions in determining community structures and exchange of genetic materials. This simplified model elucidates a mechanism of microbial herd protection by which competing antagonistic species coexist in the same niche despite their diverse mutually destructive activities. Our results also suggest that antagonistic interaction imposes a strong selection that could promote multicellular like social behaviors and contribute to the transition to multicellularity during evolution.}, } @article {pmid27629030, year = {2016}, author = {Wensink, MJ}, title = {Size, longevity and cancer: age structure.}, journal = {Proceedings. Biological sciences}, volume = {283}, number = {1838}, pages = {}, pmid = {27629030}, issn = {1471-2954}, mesh = {Animals ; *Body Size ; Humans ; *Longevity ; Models, Biological ; *Neoplasms ; Probability ; }, abstract = {There is significant recent interest in Peto's paradox and the related problem of the evolution of large, long-lived organisms in terms of cancer robustness. Peto's paradox refers to the expectation that large, long-lived organisms have a higher lifetime cancer risk, which is not the case: a paradox. This paradox, however, is circular: large, long-lived organisms are large and long-lived because they are cancer robust. Lifetime risk, meanwhile, depends on the age distributions of both cancer and competing risks: if cancer strikes before competing risks, then lifetime risk is high; if not, not. Because no set of competing risks is generally prevalent, it is instructive to temporarily dispose of competing risks and investigate the pure age dynamics of cancer under the multistage model of carcinogenesis. In addition to augmenting earlier results, I show that in terms of cancer-free lifespan large organisms reap greater benefits from an increase in cellular cancer robustness than smaller organisms. Conversely, a higher cellular cancer robustness renders cancer-free lifespan more resilient to an increase in size. This interaction may be an important driver of the evolution of large, cancer-robust organisms.}, } @article {pmid27628442, year = {2016}, author = {Li, S and Hauser, F and Skadborg, SK and Nielsen, SV and Kirketerp-Møller, N and Grimmelikhuijzen, CJ}, title = {Adipokinetic hormones and their G protein-coupled receptors emerged in Lophotrochozoa.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {32789}, pmid = {27628442}, issn = {2045-2322}, mesh = {Adipokines/*metabolism ; Animals ; *Biological Evolution ; CHO Cells ; Cloning, Molecular ; Computational Biology ; Crassostrea/metabolism ; Cricetinae ; Cricetulus ; Drosophila melanogaster ; Gonadotropin-Releasing Hormone/metabolism ; Humans ; Insect Hormones/*metabolism ; Insect Proteins/metabolism ; Insecta ; Invertebrates/*metabolism ; Ligands ; Neuropeptides/metabolism ; Oligopeptides/*metabolism ; Peptides/metabolism ; Phylogeny ; Pyrrolidonecarboxylic Acid/*analogs & derivatives/metabolism ; Receptors, G-Protein-Coupled/*metabolism ; Signal Transduction ; }, abstract = {Most multicellular animals belong to two evolutionary lineages, the Proto- and Deuterostomia, which diverged 640-760 million years (MYR) ago. Neuropeptide signaling is abundant in animals belonging to both lineages, but it is often unclear whether there exist evolutionary relationships between the neuropeptide systems used by proto- or deuterostomes. An exception, however, are members of the gonadotropin-releasing hormone (GnRH) receptor superfamily, which occur in both evolutionary lineages, where GnRHs are the ligands in Deuterostomia and GnRH-like peptides, adipokinetic hormone (AKH), corazonin, and AKH/corazonin-related peptide (ACP) are the ligands in Protostomia. AKH is a well-studied insect neuropeptide that mobilizes lipids and carbohydrates from the insect fat body during flight. In our present paper, we show that AKH is not only widespread in insects, but also in other Ecdysozoa and in Lophotrochozoa. Furthermore, we have cloned and deorphanized two G protein-coupled receptors (GPCRs) from the oyster Crassostrea gigas (Mollusca) that are activated by low nanomolar concentrations of oyster AKH (pQVSFSTNWGSamide). Our discovery of functional AKH receptors in molluscs is especially significant, because it traces the emergence of AKH signaling back to about 550 MYR ago and brings us closer to a more complete understanding of the evolutionary origins of the GnRH receptor superfamily.}, } @article {pmid27621281, year = {2016}, author = {Yu, YN and Kleiner, M and Velicer, GJ}, title = {Spontaneous Reversions of an Evolutionary Trait Loss Reveal Regulators of a Small RNA That Controls Multicellular Development in Myxobacteria.}, journal = {Journal of bacteriology}, volume = {198}, number = {23}, pages = {3142-3151}, pmid = {27621281}, issn = {1098-5530}, support = {R01 GM079690/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/genetics/metabolism ; Biological Evolution ; *Gene Expression Regulation, Bacterial ; Gene Expression Regulation, Developmental ; Histidine Kinase/genetics/metabolism ; Mutation ; Myxococcus xanthus/*genetics/*growth & development/metabolism ; RNA, Bacterial/genetics/*metabolism ; }, abstract = {UNLABELLED: Lost traits can reevolve, but the probability of trait reversion depends partly on a trait's genetic complexity. Myxobacterial fruiting body development is a complex trait controlled by the small RNA (sRNA) Pxr, which blocks development under conditions of nutrient abundance. In developmentally proficient strains of Myxococcus xanthus, starvation relaxes the inhibition by Pxr, thereby allowing development to proceed. In contrast, the lab-evolved strain OC does not develop because it fails to relay an early starvation signal that alleviates inhibition by Pxr. A descendant of OC, strain PX, previously reevolved developmental proficiency via a mutation in pxr that inactivates its function. A single-colony screen was used to test whether reversion of OC to developmental proficiency occurs only by mutation of pxr or might also occur through alternative regulatory loci. Five spontaneous mutants of OC that exhibited restored development were isolated, and all five showed defects in Pxr synthesis, structure, or processing, including one that incurred an eight-nucleotide deletion in pxr Two mutations occurred in the σ[54] response regulator (RR) gene MXAN_1078 (named pxrR here), immediately upstream of pxr PxrR was found to positively regulate pxr transcription, presumably via the σ[54] promoter of pxr Two other mutations were identified in a histidine kinase (HK) gene (MXAN_1077; named pxrK here) immediately upstream of pxrR Evolutionarily, the rate of trait restoration documented in this study suggests that reversion of social defects in natural microbial populations may be common. Molecularly, these results suggest a mechanism by which the regulatory functions of an HK-RR two-component signaling system and an sRNA are integrated to control initiation of myxobacterial development.

IMPORTANCE: Many myxobacteria initiate a process of multicellular fruiting body development upon starvation, but key features of the regulatory network controlling the transition from growth to development remain obscure. Previous work with Myxococcus xanthus identified the first small RNA (sRNA) regulator (Pxr) known to serve as a gatekeeper in this life history transition, as it blocks development when nutrients are abundant. In the present study, a screen for spontaneous mutants of M. xanthus was developed that revealed a two-component system operon (encoding a histidine kinase and a σ[54] response regulator) associated with the production and processing of Pxr sRNA. This discovery broadens our knowledge of early developmental gene regulation and also represents an evolutionary integration of two-component signaling and sRNA gene regulation to control a bacterial social trait.}, } @article {pmid27619696, year = {2016}, author = {Lehtonen, J and Kokko, H and Parker, GA}, title = {What do isogamous organisms teach us about sex and the two sexes?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1706}, pages = {}, pmid = {27619696}, issn = {1471-2970}, mesh = {*Biological Evolution ; Eukaryota/*physiology ; Germ Cells/*physiology ; Reproduction ; *Sex ; }, abstract = {Isogamy is a reproductive system where all gametes are morphologically similar, especially in terms of size. Its importance goes beyond specific cases: to this day non-anisogamous systems are common outside of multicellular animals and plants, they can be found in all eukaryotic super-groups, and anisogamous organisms appear to have isogamous ancestors. Furthermore, because maleness is synonymous with the production of small gametes, an explanation for the initial origin of males and females is synonymous with understanding the transition from isogamy to anisogamy. As we show here, this transition may also be crucial for understanding why sex itself remains common even in taxa with high costs of male production (the twofold cost of sex). The transition to anisogamy implies the origin of male and female sexes, kickstarts the subsequent evolution of sex roles, and has a major impact on the costliness of sexual reproduction. Finally, we combine some of the consequences of isogamy and anisogamy in a thought experiment on the maintenance of sexual reproduction. We ask what happens if there is a less than twofold benefit to sex (not an unlikely scenario as large short-term benefits have proved difficult to find), and argue that this could lead to a situation where lineages that evolve anisogamy-and thus the highest costs of sex-end up being associated with constraints that make invasion by asexual reproduction unlikely (the 'anisogamy gateway' hypothesis).This article is part of the themed issue 'Weird sex: the underappreciated diversity of sexual reproduction'.}, } @article {pmid27617970, year = {2016}, author = {Bowman, JL and Sakakibara, K and Furumizu, C and Dierschke, T}, title = {Evolution in the Cycles of Life.}, journal = {Annual review of genetics}, volume = {50}, number = {}, pages = {133-154}, doi = {10.1146/annurev-genet-120215-035227}, pmid = {27617970}, issn = {1545-2948}, mesh = {*Biological Evolution ; Bryophyta/genetics ; Chlorophyta/genetics ; Diploidy ; Eukaryota ; Fungi/genetics ; Haploidy ; Homeodomain Proteins/genetics ; Magnoliopsida/genetics ; Phaeophyta/genetics ; Phylogeny ; Plants/*genetics ; Rhodophyta/genetics ; }, abstract = {The life cycles of eukaryotes alternate between haploid and diploid phases, which are initiated by meiosis and gamete fusion, respectively. In both ascomycete and basidiomycete fungi and chlorophyte algae, the haploid-to-diploid transition is regulated by a pair of paralogous homeodomain protein encoding genes. That a common genetic program controls the haploid-to-diploid transition in phylogenetically disparate eukaryotic lineages suggests this may be the ancestral function for homeodomain proteins. Multicellularity has evolved independently in many eukaryotic lineages in either one or both phases of the life cycle. Organisms, such as land plants, exhibiting a life cycle whereby multicellular bodies develop in both the haploid and diploid phases are often referred to as possessing an alternation of generations. We review recent progress on understanding the genetic basis for the land plant alternation of generations and highlight the roles that homeodomain-encoding genes may have played in the evolution of complex multicellularity in this lineage.}, } @article {pmid27617059, year = {2016}, author = {Robbins, RJ and Krishtalka, L and Wooley, JC}, title = {Advances in biodiversity: metagenomics and the unveiling of biological dark matter.}, journal = {Standards in genomic sciences}, volume = {11}, number = {1}, pages = {69}, pmid = {27617059}, issn = {1944-3277}, abstract = {BACKGROUND: Efforts to harmonize genomic data standards used by the biodiversity and metagenomic research communities have shown that prokaryotic data cannot be understood or represented in a traditional, classical biological context for conceptual reasons, not technical ones.

RESULTS: Biology, like physics, has a fundamental duality-the classical macroscale eukaryotic realm vs. the quantum microscale microbial realm-with the two realms differing profoundly, and counter-intuitively, from one another. Just as classical physics is emergent from and cannot explain the microscale realm of quantum physics, so classical biology is emergent from and cannot explain the microscale realm of prokaryotic life. Classical biology describes the familiar, macroscale realm of multi-cellular eukaryotic organisms, which constitute a highly derived and constrained evolutionary subset of the biosphere, unrepresentative of the vast, mostly unseen, microbial world of prokaryotic life that comprises at least half of the planet's biomass and most of its genetic diversity. The two realms occupy fundamentally different mega-niches: eukaryotes interact primarily mechanically with the environment, prokaryotes primarily physiologically. Further, many foundational tenets of classical biology simply do not apply to prokaryotic biology.

CONCLUSIONS: Classical genetics one held that genes, arranged on chromosomes like beads on a string, were the fundamental units of mutation, recombination, and heredity. Then, molecular analysis showed that there were no fundamental units, no beads, no string. Similarly, classical biology asserts that individual organisms and species are fundamental units of ecology, evolution, and biodiversity, composing an evolutionary history of objectively real, lineage-defined groups in a single-rooted tree of life. Now, metagenomic tools are forcing a recognition that there are no completely objective individuals, no unique lineages, and no one true tree. The newly revealed biosphere of microbial dark matter cannot be understood merely by extending the concepts and methods of eukaryotic macrobiology. The unveiling of biological dark matter is allowing us to see, for the first time, the diversity of the entire biosphere and, to paraphrase Darwin, is providing a new view of life. Advancing and understanding that view will require major revisions to some of the most fundamental concepts and theories in biology.}, } @article {pmid27609894, year = {2016}, author = {Sunyer, R and Conte, V and Escribano, J and Elosegui-Artola, A and Labernadie, A and Valon, L and Navajas, D and García-Aznar, JM and Muñoz, JJ and Roca-Cusachs, P and Trepat, X}, title = {Collective cell durotaxis emerges from long-range intercellular force transmission.}, journal = {Science (New York, N.Y.)}, volume = {353}, number = {6304}, pages = {1157-1161}, doi = {10.1126/science.aaf7119}, pmid = {27609894}, issn = {1095-9203}, mesh = {Cell Line ; Epithelial Cells/*physiology ; *Extracellular Matrix ; Humans ; Intercellular Junctions/physiology ; Microscopy, Phase-Contrast ; Myosins/physiology ; *Taxis Response ; }, abstract = {The ability of cells to follow gradients of extracellular matrix stiffness-durotaxis-has been implicated in development, fibrosis, and cancer. Here, we found multicellular clusters that exhibited durotaxis even if isolated constituent cells did not. This emergent mode of directed collective cell migration applied to a variety of epithelial cell types, required the action of myosin motors, and originated from supracellular transmission of contractile physical forces. To explain the observed phenomenology, we developed a generalized clutch model in which local stick-slip dynamics of cell-matrix adhesions was integrated to the tissue level through cell-cell junctions. Collective durotaxis is far more efficient than single-cell durotaxis; it thus emerges as a robust mechanism to direct cell migration during development, wound healing, and collective cancer cell invasion.}, } @article {pmid27595342, year = {2017}, author = {Ishizaki, K}, title = {Evolution of land plants: insights from molecular studies on basal lineages.}, journal = {Bioscience, biotechnology, and biochemistry}, volume = {81}, number = {1}, pages = {73-80}, doi = {10.1080/09168451.2016.1224641}, pmid = {27595342}, issn = {1347-6947}, mesh = {Embryophyta/*genetics/metabolism ; *Evolution, Molecular ; Introduced Species ; }, abstract = {The invasion of the land by plants, or terrestrialization, was one of the most critical events in the history of the Earth. The evolution of land plants included significant transformations in body plans: the emergence of a multicellular diploid sporophyte, transition from gametophyte-dominant to sporophyte-dominant life histories, and development of many specialized tissues and organs, such as stomata, vascular tissues, roots, leaves, seeds, and flowers. Recent advances in molecular genetics in two model basal plants, bryophytes Physcomitrella patens and Marchantia polymorpha, have begun to provide answers to several key questions regarding land plant evolution. This paper discusses the evolution of the genes and regulatory mechanisms that helped drive such significant morphological innovations among land-based plants.}, } @article {pmid27589960, year = {2016}, author = {Lee, J and Cho, CH and Park, SI and Choi, JW and Song, HS and West, JA and Bhattacharya, D and Yoon, HS}, title = {Parallel evolution of highly conserved plastid genome architecture in red seaweeds and seed plants.}, journal = {BMC biology}, volume = {14}, number = {}, pages = {75}, pmid = {27589960}, issn = {1741-7007}, mesh = {Conserved Sequence/*genetics ; Cycadopsida/*genetics ; *Evolution, Molecular ; Genetic Variation ; *Genome, Plastid ; Magnoliopsida/*genetics ; Multigene Family ; Phylogeny ; Rhodophyta/*genetics ; Seeds/*genetics ; Synteny/genetics ; }, abstract = {BACKGROUND: The red algae (Rhodophyta) diverged from the green algae and plants (Viridiplantae) over one billion years ago within the kingdom Archaeplastida. These photosynthetic lineages provide an ideal model to study plastid genome reduction in deep time. To this end, we assembled a large dataset of the plastid genomes that were available, including 48 from the red algae (17 complete and three partial genomes produced for this analysis) to elucidate the evolutionary history of these organelles.

RESULTS: We found extreme conservation of plastid genome architecture in the major lineages of the multicellular Florideophyceae red algae. Only three minor structural types were detected in this group, which are explained by recombination events of the duplicated rDNA operons. A similar high level of structural conservation (although with different gene content) was found in seed plants. Three major plastid genome architectures were identified in representatives of 46 orders of angiosperms and three orders of gymnosperms.

CONCLUSIONS: Our results provide a comprehensive account of plastid gene loss and rearrangement events involving genome architecture within Archaeplastida and lead to one over-arching conclusion: from an ancestral pool of highly rearranged plastid genomes in red and green algae, the aquatic (Florideophyceae) and terrestrial (seed plants) multicellular lineages display high conservation in plastid genome architecture. This phenomenon correlates with, and could be explained by, the independent and widely divergent (separated by >400 million years) origins of complex sexual cycles and reproductive structures that led to the rapid diversification of these lineages.}, } @article {pmid27579832, year = {2016}, author = {Xu, Y and Yu, XL and Hu, CM and Hao, G}, title = {Morphological and Molecular Phylogenetic Data Reveal a New Species of Primula (Primulaceae) from Hunan, China.}, journal = {PloS one}, volume = {11}, number = {8}, pages = {e0161172}, pmid = {27579832}, issn = {1932-6203}, mesh = {China ; Genetic Markers ; *Phylogeny ; Plant Proteins/*genetics ; *Primula/anatomy & histology/classification/genetics ; }, abstract = {A new species of Primulaceae, Primula undulifolia, is described from the hilly area of Hunan province in south-central China. Its morphology and distributional range suggest that it is allied to P. kwangtungensis, both adapted to subtropical climate, having contiguous distribution and similar habitat, growing on shady and moist cliffs. Petioles, scapes and pedicels of them are densely covered with rusty multicellular hairs, but the new species can be easily distinguished by its smaller flowers and narrowly oblong leaves with undulate margins. Molecular phylogenetic analysis based on four DNA markers (ITS, matK, trnL-F and rps16) confirmed the new species as an independent lineage and constitutes a main clade together with P. kwangtungensis, P. kweichouensis, P. wangii and P. hunanensis of Primula sect. Carolinella.}, } @article {pmid27571751, year = {2016}, author = {Leducq, JB and Nielly-Thibault, L and Charron, G and Eberlein, C and Verta, JP and Samani, P and Sylvester, K and Hittinger, CT and Bell, G and Landry, CR}, title = {Speciation driven by hybridization and chromosomal plasticity in a wild yeast.}, journal = {Nature microbiology}, volume = {1}, number = {}, pages = {15003}, pmid = {27571751}, issn = {2058-5276}, mesh = {*Chromosomes, Fungal ; Forests ; *Genetic Speciation ; *Genetic Variation ; *Hybridization, Genetic ; North America ; *Recombination, Genetic ; Saccharomyces/*classification/*genetics/isolation & purification ; }, abstract = {Hybridization is recognized as a powerful mechanism of speciation and a driving force in generating biodiversity. However, only few multicellular species, limited to a handful of plants and animals, have been shown to fulfil all the criteria of homoploid hybrid speciation. This lack of evidence could lead to the interpretation that speciation by hybridization has a limited role in eukaryotes, particularly in single-celled organisms. Laboratory experiments have revealed that fungi such as budding yeasts can rapidly develop reproductive isolation and novel phenotypes through hybridization, showing that in principle homoploid speciation could occur in nature. Here, we report a case of homoploid hybrid speciation in natural populations of the budding yeast Saccharomyces paradoxus inhabiting the North American forests. We show that the rapid evolution of chromosome architecture and an ecological context that led to secondary contact between nascent species drove the formation of an incipient hybrid species with a potentially unique ecological niche.}, } @article {pmid27559062, year = {2016}, author = {Schoustra, S and Hwang, S and Krug, J and de Visser, JA}, title = {Diminishing-returns epistasis among random beneficial mutations in a multicellular fungus.}, journal = {Proceedings. Biological sciences}, volume = {283}, number = {1837}, pages = {}, pmid = {27559062}, issn = {1471-2954}, mesh = {Aspergillus nidulans/*genetics ; *Epistasis, Genetic ; *Genetic Fitness ; Genotype ; Models, Genetic ; *Mutation ; }, abstract = {Adaptive evolution ultimately is fuelled by mutations generating novel genetic variation. Non-additivity of fitness effects of mutations (called epistasis) may affect the dynamics and repeatability of adaptation. However, understanding the importance and implications of epistasis is hampered by the observation of substantial variation in patterns of epistasis across empirical studies. Interestingly, some recent studies report increasingly smaller benefits of beneficial mutations once genotypes become better adapted (called diminishing-returns epistasis) in unicellular microbes and single genes. Here, we use Fisher's geometric model (FGM) to generate analytical predictions about the relationship between the effect size of mutations and the extent of epistasis. We then test these predictions using the multicellular fungus Aspergillus nidulans by generating a collection of 108 strains in either a poor or a rich nutrient environment that each carry a beneficial mutation and constructing pairwise combinations using sexual crosses. Our results support the predictions from FGM and indicate negative epistasis among beneficial mutations in both environments, which scale with mutational effect size. Hence, our findings show the importance of diminishing-returns epistasis among beneficial mutations also for a multicellular organism, and suggest that this pattern reflects a generic constraint operating at diverse levels of biological organization.}, } @article {pmid27549405, year = {2016}, author = {Rödelsperger, C and Menden, K and Serobyan, V and Witte, H and Baskaran, P}, title = {First insights into the nature and evolution of antisense transcription in nematodes.}, journal = {BMC evolutionary biology}, volume = {16}, number = {1}, pages = {165}, pmid = {27549405}, issn = {1471-2148}, mesh = {Animals ; Biological Evolution ; Evolution, Molecular ; Gene Expression Regulation ; Gene Library ; Genes, Helminth ; *Introns ; Nematoda/*genetics ; Proteomics ; RNA, Antisense/*genetics ; Synteny ; Transcription, Genetic ; }, abstract = {BACKGROUND: The development of multicellular organisms is coordinated by various gene regulatory mechanisms that ensure correct spatio-temporal patterns of gene expression. Recently, the role of antisense transcription in gene regulation has moved into focus of research. To characterize genome-wide patterns of antisense transcription and to study their evolutionary conservation, we sequenced a strand-specific RNA-seq library of the nematode Pristionchus pacificus.

RESULTS: We identified 1112 antisense configurations of which the largest group represents 465 antisense transcripts (ASTs) that are fully embedded in introns of their host genes. We find that most ASTs show homology to protein-coding genes and are overrepresented in proteomic data. Together with the finding, that expression levels of ASTs and host genes are uncorrelated, this indicates that most ASTs in P. pacificus do not represent non-coding RNAs and do not exhibit regulatory functions on their host genes. We studied the evolution of antisense gene pairs across 20 nematode genomes, showing that the majority of pairs is lineage-specific and even the highly conserved vps-4, ddx-27, and sel-2 loci show abundant structural changes including duplications, deletions, intron gains and loss of antisense transcription. In contrast, host genes in general, are remarkably conserved and encode exceptionally long introns leading to unusually large blocks of conserved synteny.

CONCLUSIONS: Our study has shown that in P. pacificus antisense transcription as such does not define non-coding RNAs but is rather a feature of highly conserved genes with long introns. We hypothesize that the presence of regulatory elements imposes evolutionary constraint on the intron length, but simultaneously, their large size makes them a likely target for translocation of genomic elements including protein-coding genes that eventually end up as ASTs.}, } @article {pmid27534782, year = {2016}, author = {Šmardová, J and Koptíková, J}, title = {[Two Approaches to Cancer Development].}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {29}, number = {4}, pages = {259-266}, doi = {10.14735/amko2016259}, pmid = {27534782}, issn = {0862-495X}, mesh = {Carcinogenesis/*genetics ; Cell Proliferation/*genetics ; Epigenesis, Genetic/genetics ; Humans ; Mutation/*genetics ; Neoplasms/*genetics ; Tumor Microenvironment ; }, abstract = {BACKGROUND: The somatic mutation theory explaining the process of carcinogenesis is generally accepted. The theory postulates that carcinogenesis begins in a first renegade cell that undergoes gradual transformation from a healthy to a fully malignant state through the accumulation of genetic and epigenetic "hits". This theory focuses specifically on mutations and genetic aberrations, and their impact on cells. It considers tumors as populations of sick cells that lose control of their own proliferation. The theory was put forward by Robert Weinberg and Douglas Hanahan, and is the predominant view in current cancer biology. By contrast, the tissue organization field theory proposed by Carlos Sonnenschein and Ana Soto considers loss of physiological structure and function by a tissue as key events in tumor development. According to this theory, tumors arise at a tissue rather than at a cellular level. It is based on a presumption that proliferation status, rather than quiescence, is the default position of cells in multicellular organisms.

AIM: The article aims to provide answers to following questions: Are the views of proponents of the somatic mutation theory (the reductionists) and proponents of the tissue organization field theory (the organicists) incompatible and incommensurable, even when the mainstream of tumor biology has shifted its attention from tumor cells toward the tumor microenvironment? Where to find a third interconnecting systemic approach? Is it useful to be aware of the controversy between reductionists and organicists? What this awareness contributes to? How do these alternative views influence practical oncology and tumor biology in general?

CONCLUSION: Whether the true position is held by reductionists or organicists is unimportant. What is important is to be aware of the existence of these two concepts because this knowledge makes the way we think about tumor origin and development, and how we set up and interpret our experiments, more precise.

KEY WORDS: carcinogenesis - mutation - cell - tissues - cell proliferation - cell quiescenceThis study was supported by grant of Internal Grant Agency of the Czech ministry of Health No. NT/13784-4/2012.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 29. 7. 2015Accepted: 27. 4. 2016.}, } @article {pmid27534726, year = {2016}, author = {Torday, JS}, title = {The Emergence of Physiology and Form: Natural Selection Revisited.}, journal = {Biology}, volume = {5}, number = {2}, pages = {}, pmid = {27534726}, issn = {2079-7737}, support = {R01 HL055268/HL/NHLBI NIH HHS/United States ; }, abstract = {Natural Selection describes how species have evolved differentially, but it is descriptive, non-mechanistic. What mechanisms does Nature use to accomplish this feat? One known way in which ancient natural forces affect development, phylogeny and physiology is through gravitational effects that have evolved as mechanotransduction, seen in the lung, kidney and bone, linking as molecular homologies to skin and brain. Tracing the ontogenetic and phylogenetic changes that have facilitated mechanotransduction identifies specific homologous cell-types and functional molecular markers for lung homeostasis that reveal how and why complex physiologic traits have evolved from the unicellular to the multicellular state. Such data are reinforced by their reverse-evolutionary patterns in chronic degenerative diseases. The physiologic responses of model organisms like Dictyostelium and yeast to gravity provide deep comparative molecular phenotypic homologies, revealing mammalian Target of Rapamycin (mTOR) as the final common pathway for vertical integration of vertebrate physiologic evolution; mTOR integrates calcium/lipid epistatic balance as both the proximate and ultimate positive selection pressure for vertebrate physiologic evolution. The commonality of all vertebrate structure-function relationships can be reduced to calcium/lipid homeostatic regulation as the fractal unit of vertebrate physiology, demonstrating the primacy of the unicellular state as the fundament of physiologic evolution.}, } @article {pmid27518838, year = {2016}, author = {El Kafsi, H and Gorochov, G and Larsen, M}, title = {Host genetics affect microbial ecosystems via host immunity.}, journal = {Current opinion in allergy and clinical immunology}, volume = {16}, number = {5}, pages = {413-420}, doi = {10.1097/ACI.0000000000000302}, pmid = {27518838}, issn = {1473-6322}, mesh = {Animals ; Biological Evolution ; Ecosystem ; *Gene-Environment Interaction ; *Genetic Phenomena ; Homeostasis ; *Host-Pathogen Interactions ; Humans ; Immunity/*genetics ; Mice ; *Microbiota ; Symbiosis ; }, abstract = {PURPOSE OF REVIEW: Genetic evolution of multicellular organisms has occurred in response to environmental challenges, including competition for nutrients, climate change, physical and chemical stressors, and pathogens. However, fitness of an organism is dependent not only on defense efficacy, but also on the ability to take advantage of symbiotic organisms. Indeed, microbes not only encompass pathogenicity, but also enable efficient nutrient uptake from diets nondegradable by the host itself. Moreover, microbes play important roles in the development of host immunity. Here we review associations between specific host genes and variance in microbiota composition and compare with interactions between microbes and host immunity.

RECENT FINDINGS: Recent genome-wide association studies reveal that symbiosis between host and microbiota is the exquisite result of genetic coevolution. Moreover, a subset of microbes from human and mouse microbiota have been identified to interact with humoral and cellular immunity. Interestingly, microbes associated with both host genetics and host immunity are taxonomically related. Most involved are Bifidobacterium, Lactobacillus, and Akkermansia, which are dually associated with both host immunity and host genetics.

SUMMARY: We conclude that future therapeutics targeting microbiota in the context of chronic inflammatory diseases need to consider both immune and genetic host features associated with microbiota homeostasis.}, } @article {pmid27512113, year = {2016}, author = {Derelle, R and López-García, P and Timpano, H and Moreira, D}, title = {A Phylogenomic Framework to Study the Diversity and Evolution of Stramenopiles (=Heterokonts).}, journal = {Molecular biology and evolution}, volume = {33}, number = {11}, pages = {2890-2898}, pmid = {27512113}, issn = {1537-1719}, support = {322669/ERC_/European Research Council/International ; }, mesh = {*Biological Evolution ; DNA, Ribosomal/genetics ; Diatoms/genetics ; Evolution, Molecular ; Heterotrophic Processes ; Phylogeny ; Sequence Analysis, DNA/methods ; Stramenopiles/*genetics ; }, abstract = {Stramenopiles or heterokonts constitute one of the most speciose and diverse clades of protists. It includes ecologically important algae (such as diatoms or large multicellular brown seaweeds), as well as heterotrophic (e.g., bicosoecids, MAST groups) and parasitic (e.g., Blastocystis, oomycetes) species. Despite their evolutionary and ecological relevance, deep phylogenetic relationships among stramenopile groups, inferred mostly from small-subunit rDNA phylogenies, remain unresolved, especially for the heterotrophic taxa. Taking advantage of recently released stramenopile transcriptome and genome sequences, as well as data from the genomic assembly of the MAST-3 species Incisomonas marina generated in our laboratory, we have carried out the first extensive phylogenomic analysis of stramenopiles, including representatives of most major lineages. Our analyses, based on a large data set of 339 widely distributed proteins, strongly support a root of stramenopiles lying between two clades, Bigyra and Gyrista (Pseudofungi plus Ochrophyta). Additionally, our analyses challenge the Phaeista-Khakista dichotomy of photosynthetic stramenopiles (ochrophytes) as two groups previously considered to be part of the Phaeista (Pelagophyceae and Dictyochophyceae), branch with strong support with the Khakista (Bolidophyceae and Diatomeae). We propose a new classification of ochrophytes within the two groups Chrysista and Diatomista to reflect the new phylogenomic results. Our stramenopile phylogeny provides a robust phylogenetic framework to investigate the evolution and diversification of this group of ecologically relevant protists.}, } @article {pmid27510329, year = {2017}, author = {Pesce, M and Santoro, R}, title = {Feeling the right force: How to contextualize the cell mechanical behavior in physiologic turnover and pathologic evolution of the cardiovascular system.}, journal = {Pharmacology & therapeutics}, volume = {171}, number = {}, pages = {75-82}, doi = {10.1016/j.pharmthera.2016.08.002}, pmid = {27510329}, issn = {1879-016X}, mesh = {Animals ; Cardiovascular Diseases/*physiopathology ; Cardiovascular System/*cytology/metabolism/physiopathology ; Cell Differentiation/*physiology ; Cell Engineering/methods ; Embryonic Development/physiology ; Gene Expression/physiology ; Humans ; }, abstract = {Although traditionally linked to the physiology of tissues in 'motion', the ability of the cells to transduce external forces into coordinated gene expression programs is emerging as an integral component of the fundamental structural organization of multicellular organisms with consequences for cell differentiation even from the beginning of embryonic development. The ability of the cells to 'feel' the surrounding mechanical environment, even in the absence of tissue motion, is then translated into 'positional' or 'social' sensing that instructs, before the organ renewal, the correct patterning of the embryos. In the present review, we will highlight how these basic concepts, emerging from the employment of novel cell engineering tools, can be linked to pathophysiology of the cardiovascular system, and may contribute to understanding the molecular bases of some of the major cardiovascular diseases like heart failure, heart valve stenosis and failure of the venous aorto-coronary bypass.}, } @article {pmid27504112, year = {2016}, author = {Beilby, MJ}, title = {Multi-Scale Characean Experimental System: From Electrophysiology of Membrane Transporters to Cell-to-Cell Connectivity, Cytoplasmic Streaming and Auxin Metabolism.}, journal = {Frontiers in plant science}, volume = {7}, number = {}, pages = {1052}, pmid = {27504112}, issn = {1664-462X}, abstract = {The morphology of characean algae could be mistaken for a higher plant: stem-like axes with leaf-like branchlets anchored in the soil by root-like rhizoids. However, all of these structures are made up of giant multinucleate cells separated by multicellular nodal complexes. The excised internodal cells survive long enough for the nodes to give rise to new thallus. The size of the internodes and their thick cytoplasmic layer minimize impalement injury and allow specific micro-electrode placement. The cell structure can be manipulated by centrifugation, perfusion of cell contents or creation of cytoplasmic droplets, allowing access to both vacuolar and cytoplasmic compartments and both sides of the cell membranes. Thousands of electrical measurements on intact or altered cells and cytoplasmic droplets laid down basis to modern plant electrophysiology. Furthermore, the giant internodal cells and whole thalli facilitate research into many other plant properties. As nutrients have to be transported from rhizoids to growing parts of the thallus and hormonal signals need to pass from cell to cell, Characeae possess very fast cytoplasmic streaming. The mechanism was resolved in the characean model. Plasmodesmata between the internodal cells and nodal complexes facilitate transport of ions, nutrients and photosynthates across the nodes. The internal structure was found to be similar to those of higher plants. Recent experiments suggest a strong circadian influence on metabolic pathways producing indole-3-acetic acid (IAA) and serotonin/melatonin. The review will discuss the impact of the characean models arising from fragments of cells, single cells, cell-to-cell transport or whole thalli on understanding of plant evolution and physiology.}, } @article {pmid27501943, year = {2016}, author = {Sojo, V and Dessimoz, C and Pomiankowski, A and Lane, N}, title = {Membrane Proteins Are Dramatically Less Conserved than Water-Soluble Proteins across the Tree of Life.}, journal = {Molecular biology and evolution}, volume = {33}, number = {11}, pages = {2874-2884}, pmid = {27501943}, issn = {1537-1719}, support = {BB/L018241/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adaptation, Biological ; Archaea/genetics ; Bacteria/genetics ; Biological Evolution ; Databases, Protein ; Eukaryota/genetics ; Evolution, Molecular ; Homeostasis ; Membrane Proteins/*genetics/metabolism ; Phylogeny ; Prokaryotic Cells ; Proteins/*genetics/metabolism ; Sequence Analysis, Protein/*methods ; Solubility ; Water/metabolism ; }, abstract = {Membrane proteins are crucial in transport, signaling, bioenergetics, catalysis, and as drug targets. Here, we show that membrane proteins have dramatically fewer detectable orthologs than water-soluble proteins, less than half in most species analyzed. This sparse distribution could reflect rapid divergence or gene loss. We find that both mechanisms operate. First, membrane proteins evolve faster than water-soluble proteins, particularly in their exterior-facing portions. Second, we demonstrate that predicted ancestral membrane proteins are preferentially lost compared with water-soluble proteins in closely related species of archaea and bacteria. These patterns are consistent across the whole tree of life, and in each of the three domains of archaea, bacteria, and eukaryotes. Our findings point to a fundamental evolutionary principle: membrane proteins evolve faster due to stronger adaptive selection in changing environments, whereas cytosolic proteins are under more stringent purifying selection in the homeostatic interior of the cell. This effect should be strongest in prokaryotes, weaker in unicellular eukaryotes (with intracellular membranes), and weakest in multicellular eukaryotes (with extracellular homeostasis). We demonstrate that this is indeed the case. Similarly, we show that extracellular water-soluble proteins exhibit an even stronger pattern of low homology than membrane proteins. These striking differences in conservation of membrane proteins versus water-soluble proteins have important implications for evolution and medicine.}, } @article {pmid27490201, year = {2016}, author = {Denver, DR and Brown, AM and Howe, DK and Peetz, AB and Zasada, IA}, title = {Genome Skimming: A Rapid Approach to Gaining Diverse Biological Insights into Multicellular Pathogens.}, journal = {PLoS pathogens}, volume = {12}, number = {8}, pages = {e1005713}, pmid = {27490201}, issn = {1553-7374}, mesh = {Animals ; Genome ; Humans ; Nematoda/*genetics ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, } @article {pmid27477870, year = {2016}, author = {Chang, ML and Liang, KH and Ku, CL and Lo, CC and Cheng, YT and Hsu, CM and Yeh, CT and Chiu, CT}, title = {Resistin reinforces interferon λ-3 to eliminate hepatitis C virus with fine-tuning from RETN single-nucleotide polymorphisms.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {30799}, pmid = {27477870}, issn = {2045-2322}, mesh = {Adult ; Female ; Hepacivirus/*immunology ; Hepatitis C/*genetics/*immunology/therapy ; Humans ; Interferons ; *Interleukins/genetics/immunology ; Male ; *Polymorphism, Single Nucleotide ; *Resistin/genetics/immunology ; }, abstract = {The effect of resistin (RETN) on the response to anti-HCV therapy remains unclear. A prospective cohort study was performed using 655 consecutive HCV patients, of whom 513 had completed a course of interferon-based therapy. Multivariate and GEE analyses revealed four RETN single-nucleotide polymorphisms (SNPs), rs34861192, rs3219175, rs3745367 and rs1423096, to be synergistically associated with resistin levels. After adjusting for co-factors such as interferon λ-3 (IFNL3)-rs12979860, the resistin level and the hyper-resistinemic genotype at the 4 RETN SNPs were positively and negatively associated with a sustained virological response (SVR), respectively. RETN-rs3745367 was in linkage disequilibrium with IFNL3-rs12979860. Compared to non-SVR patients, SVR patients had higher levels of pre-therapy resistin, primarily originating from intrahepatic lymphocytes, stellate cells, Kupffer cells, hepatic progenitor cells and hepatocytes. This difference diminished over the course of therapy, as only SVR patients exhibited a 24-week post-therapy decrease in resistin. Both resistin and IFNL3 mRNAs were upregulated, but only resistin mRNA was upregulated by recombinant resistin in peripheral blood mononuclear cells with and without hyper-resistinemic genotypes of the 4 RETN SNPs, respectively. Fine-tuned by RETN SNPs, intrahepatic, multi-cellular resistin reinforced IFNL3 in eliminating HCV via immunomodulation to counteract pro-inflammation. These results encourage the development of novel resistin-targeted anti-viral agents.}, } @article {pmid27476447, year = {2017}, author = {Jubin, T and Kadam, A and Gani, AR and Singh, M and Dwivedi, M and Begum, R}, title = {Poly ADP-ribose polymerase-1: Beyond transcription and towards differentiation.}, journal = {Seminars in cell & developmental biology}, volume = {63}, number = {}, pages = {167-179}, doi = {10.1016/j.semcdb.2016.07.027}, pmid = {27476447}, issn = {1096-3634}, mesh = {Animals ; Cell Differentiation/*genetics ; Embryonic Development/genetics ; Gene Expression Regulation ; Humans ; Models, Biological ; Poly(ADP-ribose) Polymerases/*metabolism ; *Transcription, Genetic ; }, abstract = {Gene regulation mediates the processes of cellular development and differentiation leading to the origin of different cell types each having their own signature gene expression profile. However, the compact chromatin structure and the timely recruitment of molecules involved in various signaling pathways are of prime importance for temporal and spatial gene regulation that eventually contribute towards cell type and specificity. Poly (ADP-ribose) polymerase-1 (PARP-1), a 116-kDa nuclear multitasking protein is involved in modulation of chromatin condensation leading to altered gene expression. In response to activation signals, it adds ADP-ribose units to various target proteins including itself, thus regulating various key cellular processes like DNA repair, cell death, transcription, mRNA splicing etc. This review provides insights into the role of PARP-1 in gene regulation, cell differentiation and multicellular morphogenesis. In addition, the review also explores involvement of PARP-1 in immune cells development and therapeutic possibilities to treat various human diseases.}, } @article {pmid27458581, year = {2016}, author = {Pietak, A and Levin, M}, title = {Exploring Instructive Physiological Signaling with the Bioelectric Tissue Simulation Engine.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {4}, number = {}, pages = {55}, pmid = {27458581}, issn = {2296-4185}, support = {R01 AR055993/AR/NIAMS NIH HHS/United States ; R01 HD081326/HD/NICHD NIH HHS/United States ; }, abstract = {Bioelectric cell properties have been revealed as powerful targets for modulating stem cell function, regenerative response, developmental patterning, and tumor reprograming. Spatio-temporal distributions of endogenous resting potential, ion flows, and electric fields are influenced not only by the genome and external signals but also by their own intrinsic dynamics. Ion channels and electrical synapses (gap junctions) both determine, and are themselves gated by, cellular resting potential. Thus, the origin and progression of bioelectric patterns in multicellular tissues is complex, which hampers the rational control of voltage distributions for biomedical interventions. To improve understanding of these dynamics and facilitate the development of bioelectric pattern control strategies, we developed the BioElectric Tissue Simulation Engine (BETSE), a finite volume method multiphysics simulator, which predicts bioelectric patterns and their spatio-temporal dynamics by modeling ion channel and gap junction activity and tracking changes to the fundamental property of ion concentration. We validate performance of the simulator by matching experimentally obtained data on membrane permeability, ion concentration and resting potential to simulated values, and by demonstrating the expected outcomes for a range of well-known cases, such as predicting the correct transmembrane voltage changes for perturbation of single cell membrane states and environmental ion concentrations, in addition to the development of realistic transepithelial potentials and bioelectric wounding signals. In silico experiments reveal factors influencing transmembrane potential are significantly different in gap junction-networked cell clusters with tight junctions, and identify non-linear feedback mechanisms capable of generating strong, emergent, cluster-wide resting potential gradients. The BETSE platform will enable a deep understanding of local and long-range bioelectrical dynamics in tissues, and assist the development of specific interventions to achieve greater control of pattern during morphogenesis and remodeling.}, } @article {pmid27458458, year = {2016}, author = {Zhang, X and Soldati, T}, title = {Of Amoebae and Men: Extracellular DNA Traps as an Ancient Cell-Intrinsic Defense Mechanism.}, journal = {Frontiers in immunology}, volume = {7}, number = {}, pages = {269}, pmid = {27458458}, issn = {1664-3224}, abstract = {Since the discovery of the formation of DNA-based extracellular traps (ETs) by neutrophils as an innate immune defense mechanism (1), hundreds of articles describe the involvement of ETs in physiological and pathological human and animal conditions [reviewed in Ref. (2), and the previous Frontiers Research Topic on NETosis: http://www.frontiersin.org/books/NETosis_At_the_Intersection_of_Cell_Biology_Microbiology_and_Immunology/195]. Interestingly, a few reports reveal that ETs can be formed by immune cells of more ancient organisms, as far back as the common ancestor of vertebrates and invertebrates (3). Recently, we reported that the Sentinel cells of the multicellular slug of the social amoeba Dictyostelium discoideum also produce ETs to trap and kill slug-invading bacteria [see Box 1; and Figure 1 Ref. (4)]. This is a strong evidence that DNA-based cell-intrinsic defense mechanisms emerged much earlier than thought, about 1.3 billion years ago. Amazingly, using extrusion of DNA as a weapon to capture and kill uningestable microbes has its rationale. During the emergence of multicellularity, a primitive innate immune system developed in the form of a dedicated set of specialized phagocytic cells. This professionalization of immunity allowed the evolution of sophisticated defense mechanisms including the sacrifice of a small set of cells by a mechanism related to NETosis. This altruistic behavior likely emerged in steps, starting from the release of "dispensable" mitochondrial DNA by D. discoideum Sentinel cells. Grounded in this realization, one can anticipate that in the near future, many more examples of the invention and fine-tuning of ETs by early metazoan ancestors will be identified. Consequently, it can be expected that this more complete picture of the evolution of ETs will impact our views of the involvement and pathologies linked to ETs in human and animals.}, } @article {pmid27452234, year = {2016}, author = {Kulkarni, A and Pandey, P and Rao, P and Mahmoud, A and Goldman, A and Sabbisetti, V and Parcha, S and Natarajan, SK and Chandrasekar, V and Dinulescu, D and Roy, S and Sengupta, S}, title = {Algorithm for Designing Nanoscale Supramolecular Therapeutics with Increased Anticancer Efficacy.}, journal = {ACS nano}, volume = {10}, number = {9}, pages = {8154-8168}, doi = {10.1021/acsnano.6b00241}, pmid = {27452234}, issn = {1936-086X}, support = {R01 CA135242/CA/NCI NIH HHS/United States ; }, mesh = {*Algorithms ; Molecular Dynamics Simulation ; *Nanoparticles ; Nanostructures ; Neoplasms/*therapy ; }, abstract = {In the chemical world, evolution is mirrored in the origin of nanoscale supramolecular structures from molecular subunits. The complexity of function acquired in a supramolecular system over a molecular subunit can be harnessed in the treatment of cancer. However, the design of supramolecular nanostructures is hindered by a limited atomistic level understanding of interactions between building blocks. Here, we report the development of a computational algorithm, which we term Volvox after the first multicellular organism, that sequentially integrates quantum mechanical energy-state- and force-field-based models with large-scale all-atomistic explicit water molecular dynamics simulations to design stable nanoscale lipidic supramolecular structures. In one example, we demonstrate that Volvox enables the design of a nanoscale taxane supramolecular therapeutic. In another example, we demonstrate that Volvox can be extended to optimizing the ratio of excipients to form a stable nanoscale supramolecular therapeutic. The nanoscale taxane supramolecular therapeutic exerts greater antitumor efficacy than a clinically used taxane in vivo. Volvox can emerge as a powerful tool in the design of nanoscale supramolecular therapeutics for effective treatment of cancer.}, } @article {pmid27451296, year = {2016}, author = {Matt, G and Umen, J}, title = {Volvox: A simple algal model for embryogenesis, morphogenesis and cellular differentiation.}, journal = {Developmental biology}, volume = {419}, number = {1}, pages = {99-113}, pmid = {27451296}, issn = {1095-564X}, support = {R01 GM078376/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Cycle ; Cell Lineage ; Cell Size ; Cellular Senescence ; *Models, Biological ; Morphogenesis ; Mutation ; Phylogeny ; Reproduction, Asexual ; Seeds ; Volvox/*cytology/genetics/physiology ; }, abstract = {Patterning of a multicellular body plan involves a coordinated set of developmental processes that includes cell division, morphogenesis, and cellular differentiation. These processes have been most intensively studied in animals and land plants; however, deep insight can also be gained by studying development in simpler multicellular organisms. The multicellular green alga Volvox carteri (Volvox) is an excellent model for the investigation of developmental mechanisms and their evolutionary origins. Volvox has a streamlined body plan that contains only a few thousand cells and two distinct cell types: reproductive germ cells and terminally differentiated somatic cells. Patterning of the Volvox body plan is achieved through a stereotyped developmental program that includes embryonic cleavage with asymmetric cell division, morphogenesis, and cell-type differentiation. In this review we provide an overview of how these three developmental processes give rise to the adult form in Volvox and how developmental mutants have provided insights into the mechanisms behind these events. We highlight the accessibility and tractability of Volvox and its relatives that provide a unique opportunity for studying development.}, } @article {pmid27443165, year = {2016}, author = {Punia, K and Bucaro, M and Mancuso, A and Cuttitta, C and Marsillo, A and Bykov, A and L'Amoreaux, W and Raja, KS}, title = {Rediscovering Chemical Gardens: Self-Assembling Cytocompatible Protein-Intercalated Silicate-Phosphate Sponge-Mimetic Tubules.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {32}, number = {34}, pages = {8748-8758}, doi = {10.1021/acs.langmuir.6b01721}, pmid = {27443165}, issn = {1520-5827}, mesh = {Animals ; Biocompatible Materials/*chemistry/pharmacology ; Biomimetic Materials/*chemistry/pharmacology ; Calcium Chloride/chemistry ; Cell Line ; Cell Survival/drug effects ; Dinoflagellida/drug effects/physiology ; Gelatin/*chemistry ; HeLa Cells ; Humans ; Myoblasts/cytology/drug effects/physiology ; Phosphates/*chemistry ; Porifera/anatomy & histology/chemistry ; Rats ; Silicates/*chemistry ; Tissue Engineering ; *Tissue Scaffolds ; }, abstract = {The classic chemical garden experiment is reconstructed to produce protein-intercalated silicate-phosphate tubules that resemble tubular sponges. The constructs were synthesized by seeding calcium chloride into a solution of sodium silicate-potassium phosphate and gelatin. Sponge-mimetic tubules were fabricated with varying percentages of gelatin (0-15% w/v), in diameters ranging from 200 μm to 2 mm, characterized morphologically and compositionally, functionalized with biomolecules for cell adhesion, and evaluated for cytocompatibility. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy analysis (EDS) experiments showed that the external surface of the tubules was relatively more amorphous in texture and carbon/protein-rich in comparison to the interior surface. Transmission electron microscopy (TEM) images indicate a network composed of gelatin incorporated into the inorganic scaffold. The presence of gelatin in the constructs was confirmed by infrared spectroscopy. Powder X-ray diffraction (XRD) was used to identify inorganic crystalline phases in the scaffolds that are mainly composed of Ca(OH)2, NaCl, and Ca2SiO4 along with a band corresponding to amorphous gelatin. Bioconjugation and coating protocols were developed to program the scaffolds with cues for cell adhesion, and the resulting constructs were employed for 3D cell culture of marine (Pyrocystis lunula) and mammalian (HeLa and H9C2) cell lines. The cytocompatibility of the constructs was demonstrated by live cell assays. We have successfully shown that these biomimetic materials can indeed support life; they serve as scaffolds that facilitate the attachment and assembly of individual cells to form multicellular entities, thereby revisiting the 350-year-old effort to link chemical gardens with the origins of life. Hybrid chemical garden biomaterials are programmable, readily fabricated and could be employed in tissue engineering, biomolecular materials development, 3D mammalian cell culture and by researchers investigating the origins of multicellular life.}, } @article {pmid27431528, year = {2016}, author = {Solé, R}, title = {The major synthetic evolutionary transitions.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431528}, issn = {1471-2970}, mesh = {*Artificial Intelligence ; *Biological Evolution ; Cells, Cultured/*physiology ; *Language ; Robotics ; *Synthetic Biology ; }, abstract = {Evolution is marked by well-defined events involving profound innovations that are known as 'major evolutionary transitions'. They involve the integration of autonomous elements into a new, higher-level organization whereby the former isolated units interact in novel ways, losing their original autonomy. All major transitions, which include the origin of life, cells, multicellular systems, societies or language (among other examples), took place millions of years ago. Are these transitions unique, rare events? Have they instead universal traits that make them almost inevitable when the right pieces are in place? Are there general laws of evolutionary innovation? In order to approach this problem under a novel perspective, we argue that a parallel class of evolutionary transitions can be explored involving the use of artificial evolutionary experiments where alternative paths to innovation can be explored. These 'synthetic' transitions include, for example, the artificial evolution of multicellular systems or the emergence of language in evolved communicating robots. These alternative scenarios could help us to understand the underlying laws that predate the rise of major innovations and the possibility for general laws of evolved complexity. Several key examples and theoretical approaches are summarized and future challenges are outlined.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27431524, year = {2016}, author = {Moses, M and Bezerra, G and Edwards, B and Brown, J and Forrest, S}, title = {Energy and time determine scaling in biological and computer designs.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431524}, issn = {1471-2970}, support = {T32 EB009414/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; *Basal Metabolism ; Biological Evolution ; *Electric Power Supplies ; Mammals/*physiology ; *Microcomputers ; Models, Biological ; Models, Theoretical ; Selection, Genetic ; }, abstract = {Metabolic rate in animals and power consumption in computers are analogous quantities that scale similarly with size. We analyse vascular systems of mammals and on-chip networks of microprocessors, where natural selection and human engineering, respectively, have produced systems that minimize both energy dissipation and delivery times. Using a simple network model that simultaneously minimizes energy and time, our analysis explains empirically observed trends in the scaling of metabolic rate in mammals and power consumption and performance in microprocessors across several orders of magnitude in size. Just as the evolutionary transitions from unicellular to multicellular animals in biology are associated with shifts in metabolic scaling, our model suggests that the scaling of power and performance will change as computer designs transition to decentralized multi-core and distributed cyber-physical systems. More generally, a single energy-time minimization principle may govern the design of many complex systems that process energy, materials and information.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27431523, year = {2016}, author = {Lachmann, M and Libby, E}, title = {Epigenetic inheritance systems contribute to the evolution of a germline.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431523}, issn = {1471-2970}, mesh = {*Biological Evolution ; *Cell Lineage ; *Epigenesis, Genetic ; Germ Cells/*physiology ; Heredity ; Models, Genetic ; }, abstract = {Differentiation within multicellular organisms is controlled by epigenetic markers transmitted across cell division. The process of differentiation will modify these epigenetic markers so that information that one cell type possesses can be lost in the transition to another. Many of the systems that encode these markers also exist in unicellular organisms but do not control differentiation. Thus, during the evolution of multicellularity, epigenetic inheritance systems were probably exapted for their current use in differentiation. We show that the simultaneous use of an information carrier for differentiation and transmission across generations can lead to the evolution of cell types that do not directly contribute to the progeny of the organism and ergo a germ-soma distinction. This shows that an intrinsic instability during a transition from unicellularity to multicellularity may contribute to widespread evolution of a germline and its maintenance, a phenomenon also relevant to the evolution of eusociality. The difference in epigenetic information contents between different cell lines in a multicellular organism is also relevant for the full-success cloning of higher animals, as well as for the maintenance of single germlines over evolutionary timescales.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27431522, year = {2016}, author = {Libby, E and Conlin, PL and Kerr, B and Ratcliff, WC}, title = {Stabilizing multicellularity through ratcheting.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431522}, issn = {1471-2970}, mesh = {*Adaptation, Biological ; *Biological Evolution ; Eukaryota/genetics/*physiology ; Models, Genetic ; *Selection, Genetic ; }, abstract = {The evolutionary transition to multicellularity probably began with the formation of simple undifferentiated cellular groups. Such groups evolve readily in diverse lineages of extant unicellular taxa, suggesting that there are few genetic barriers to this first key step. This may act as a double-edged sword: labile transitions between unicellular and multicellular states may facilitate the evolution of simple multicellularity, but reversion to a unicellular state may inhibit the evolution of increased complexity. In this paper, we examine how multicellular adaptations can act as evolutionary 'ratchets', limiting the potential for reversion to unicellularity. We consider a nascent multicellular lineage growing in an environment that varies between favouring multicellularity and favouring unicellularity. The first type of ratcheting mutations increase cell-level fitness in a multicellular context but are costly in a single-celled context, reducing the fitness of revertants. The second type of ratcheting mutations directly decrease the probability that a mutation will result in reversion (either as a pleiotropic consequence or via direct modification of switch rates). We show that both types of ratcheting mutations act to stabilize the multicellular state. We also identify synergistic effects between the two types of ratcheting mutations in which the presence of one creates the selective conditions favouring the other. Ratcheting mutations may play a key role in diverse evolutionary transitions in individuality, sustaining selection on the new higher-level organism by constraining evolutionary reversion.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27431521, year = {2016}, author = {Newman, SA}, title = {'Biogeneric' developmental processes: drivers of major transitions in animal evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431521}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Evolution, Molecular ; Extremities/anatomy & histology ; Fishes/anatomy & histology/*physiology ; Invertebrates/*physiology ; *Morphogenesis ; }, abstract = {Using three examples drawn from animal systems, I advance the hypothesis that major transitions in multicellular evolution often involved the constitution of new cell-based materials with unprecedented morphogenetic capabilities. I term the materials and formative processes that arise when highly evolved cells are incorporated into mesoscale matter 'biogeneric', to reflect their commonality with, and distinctiveness from, the organizational properties of non-living materials. The first transition arose by the innovation of classical cell-adhesive cadherins with transmembrane linkage to the cytoskeleton and the appearance of the morphogen Wnt, transforming some ancestral unicellular holozoans into 'liquid tissues', and thereby originating the metazoans. The second transition involved the new capabilities, within a basal metazoan population, of producing a mechanically stable basal lamina, and of planar cell polarization. This gave rise to the eumetazoans, initially diploblastic (two-layered) forms, and then with the addition of extracellular matrices promoting epithelial-mesenchymal transformation, three-layered triploblasts. The last example is the fin-to-limb transition. Here, the components of a molecular network that promoted the development of species-idiosyncratic endoskeletal elements in gnathostome ancestors are proposed to have evolved to a dynamical regime in which they constituted a Turing-type reaction-diffusion system capable of organizing the stereotypical arrays of elements of lobe-finned fish and tetrapods. The contrasting implications of the biogeneric materials-based and neo-Darwinian perspectives for understanding major evolutionary transitions are discussed.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27431520, year = {2016}, author = {Koonin, EV}, title = {Viruses and mobile elements as drivers of evolutionary transitions.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431520}, issn = {1471-2970}, mesh = {*Biological Evolution ; Interspersed Repetitive Sequences/*genetics ; Viruses/*genetics ; }, abstract = {The history of life is punctuated by evolutionary transitions which engender emergence of new levels of biological organization that involves selection acting at increasingly complex ensembles of biological entities. Major evolutionary transitions include the origin of prokaryotic and then eukaryotic cells, multicellular organisms and eusocial animals. All or nearly all cellular life forms are hosts to diverse selfish genetic elements with various levels of autonomy including plasmids, transposons and viruses. I present evidence that, at least up to and including the origin of multicellularity, evolutionary transitions are driven by the coevolution of hosts with these genetic parasites along with sharing of 'public goods'. Selfish elements drive evolutionary transitions at two distinct levels. First, mathematical modelling of evolutionary processes, such as evolution of primitive replicator populations or unicellular organisms, indicates that only increasing organizational complexity, e.g. emergence of multicellular aggregates, can prevent the collapse of the host-parasite system under the pressure of parasites. Second, comparative genomic analysis reveals numerous cases of recruitment of genes with essential functions in cellular life forms, including those that enable evolutionary transitions.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27431519, year = {2016}, author = {Elena, SF}, title = {Evolutionary transitions during RNA virus experimental evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431519}, issn = {1471-2970}, mesh = {*Biological Evolution ; Coinfection/virology ; Evolution, Molecular ; *Genome, Viral ; *Microbial Interactions ; RNA Viruses/*genetics/physiology ; }, abstract = {In their search to understand the evolution of biological complexity, John Maynard Smith and Eörs Szathmáry put forward the notion of major evolutionary transitions as those in which elementary units get together to generate something new, larger and more complex. The origins of chromosomes, eukaryotic cells, multicellular organisms, colonies and, more recently, language and technological societies are examples that clearly illustrate this notion. However, a transition may be considered as anecdotal or as major depending on the specific level of biological organization under study. In this contribution, I will argue that transitions may also be occurring at a much smaller scale of biological organization: the viral world. Not only that, but also that we can observe in real time how these major transitions take place during experimental evolution. I will review the outcome of recent evolution experiments with viruses that illustrate four major evolutionary transitions: (i) the origin of a new virus that infects an otherwise inaccessible host and completely changes the way it interacts with the host regulatory and metabolic networks, (ii) the incorporation and loss of genes, (iii) the origin of segmented genomes from a non-segmented one, and (iv) the evolution of cooperative behaviour and cheating between different viruses or strains during co-infection of the same host.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27431516, year = {2016}, author = {Solé, R}, title = {Synthetic transitions: towards a new synthesis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431516}, issn = {1471-2970}, mesh = {Biological Evolution ; Computer Simulation ; *Life ; *Physics ; *Robotics ; *Synthetic Biology ; }, abstract = {The evolution of life in our biosphere has been marked by several major innovations. Such major complexity shifts include the origin of cells, genetic codes or multicellularity to the emergence of non-genetic information, language or even consciousness. Understanding the nature and conditions for their rise and success is a major challenge for evolutionary biology. Along with data analysis, phylogenetic studies and dedicated experimental work, theoretical and computational studies are an essential part of this exploration. With the rise of synthetic biology, evolutionary robotics, artificial life and advanced simulations, novel perspectives to these problems have led to a rather interesting scenario, where not only the major transitions can be studied or even reproduced, but even new ones might be potentially identified. In both cases, transitions can be understood in terms of phase transitions, as defined in physics. Such mapping (if correct) would help in defining a general framework to establish a theory of major transitions, both natural and artificial. Here, we review some advances made at the crossroads between statistical physics, artificial life, synthetic biology and evolutionary robotics.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27412854, year = {2016}, author = {Smeds, L and Qvarnström, A and Ellegren, H}, title = {Direct estimate of the rate of germline mutation in a bird.}, journal = {Genome research}, volume = {26}, number = {9}, pages = {1211-1218}, pmid = {27412854}, issn = {1549-5469}, mesh = {Animals ; *Evolution, Molecular ; Genome ; Germ-Line Mutation/*genetics ; High-Throughput Nucleotide Sequencing ; Mutation Rate ; Pedigree ; Songbirds/*genetics ; }, abstract = {The fidelity of DNA replication together with repair mechanisms ensure that the genetic material is properly copied from one generation to another. However, on extremely rare occasions when damages to DNA or replication errors are not repaired, germline mutations can be transmitted to the next generation. Because of the rarity of these events, studying the rate at which new mutations arise across organisms has been a great challenge, especially in multicellular nonmodel organisms with large genomes. We sequenced the genomes of 11 birds from a three-generation pedigree of the collared flycatcher (Ficedula albicollis) and used highly stringent bioinformatic criteria for mutation detection and used several procedures to validate mutations, including following the stable inheritance of new mutations to subsequent generations. We identified 55 de novo mutations with a 10-fold enrichment of mutations at CpG sites and with only a modest male mutation bias. The estimated rate of mutation per site per generation was 4.6 × 10(-9), which corresponds to 2.3 × 10(-9) mutations per site per year. Compared to mammals, this is similar to mouse but about half of that reported for humans, which may be due to the higher frequency of male mutations in humans. We confirm that mutation rate scales positively with genome size and that there is a strong negative relationship between mutation rate and effective population size, in line with the drift-barrier hypothesis. Our study illustrates that it should be feasible to obtain direct estimates of the rate of mutation in essentially any organism from which family material can be obtained.}, } @article {pmid27411810, year = {2016}, author = {Cook, LM and Araujo, A and Pow-Sang, JM and Budzevich, MM and Basanta, D and Lynch, CC}, title = {Predictive computational modeling to define effective treatment strategies for bone metastatic prostate cancer.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {29384}, pmid = {27411810}, issn = {2045-2322}, support = {P30 CA076292/CA/NCI NIH HHS/United States ; R01 CA143094/CA/NCI NIH HHS/United States ; U01 CA151924/CA/NCI NIH HHS/United States ; U01 CA202958/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bone Neoplasms/*secondary/*therapy ; Bone and Bones/pathology ; Cell Differentiation ; Cell Survival ; *Computer Simulation ; Humans ; Male ; Mice ; Mice, SCID ; Neoplasm Metastasis ; Osteoblasts/cytology ; Osteoclasts/cytology ; Osteolysis ; Prostate/pathology ; Prostatic Neoplasms/*pathology/*therapy ; Transforming Growth Factor beta1/antagonists & inhibitors/*metabolism ; }, abstract = {The ability to rapidly assess the efficacy of therapeutic strategies for incurable bone metastatic prostate cancer is an urgent need. Pre-clinical in vivo models are limited in their ability to define the temporal effects of therapies on simultaneous multicellular interactions in the cancer-bone microenvironment. Integrating biological and computational modeling approaches can overcome this limitation. Here, we generated a biologically driven discrete hybrid cellular automaton (HCA) model of bone metastatic prostate cancer to identify the optimal therapeutic window for putative targeted therapies. As proof of principle, we focused on TGFβ because of its known pleiotropic cellular effects. HCA simulations predict an optimal effect for TGFβ inhibition in a pre-metastatic setting with quantitative outputs indicating a significant impact on prostate cancer cell viability, osteoclast formation and osteoblast differentiation. In silico predictions were validated in vivo with models of bone metastatic prostate cancer (PAIII and C4-2B). Analysis of human bone metastatic prostate cancer specimens reveals heterogeneous cancer cell use of TGFβ. Patient specific information was seeded into the HCA model to predict the effect of TGFβ inhibitor treatment on disease evolution. Collectively, we demonstrate how an integrated computational/biological approach can rapidly optimize the efficacy of potential targeted therapies on bone metastatic prostate cancer.}, } @article {pmid27404254, year = {2016}, author = {Durand, PM and Sym, S and Michod, RE}, title = {Programmed Cell Death and Complexity in Microbial Systems.}, journal = {Current biology : CB}, volume = {26}, number = {13}, pages = {R587-R593}, doi = {10.1016/j.cub.2016.05.057}, pmid = {27404254}, issn = {1879-0445}, mesh = {*Apoptosis ; Archaea/*physiology ; *Bacterial Physiological Phenomena ; }, abstract = {Programmed cell death (PCD) is central to organism development and for a long time was considered a hallmark of multicellularity. Its discovery, therefore, in unicellular organisms presents compelling questions. Why did PCD evolve? What is its ecological effect on communities? To answer these questions, one is compelled to consider the impacts of PCD beyond the cell, for death obviously lowers the fitness of the cell. Here, we examine the ecological effects of PCD in different microbial scenarios and conclude that PCD can increase biological complexity. In mixed microbial communities, the mode of death affects the microenvironment, impacting the interactions between taxa. Where the population comprises groups of relatives, death has a more explicit effect. Death by lysis or other means can be harmful, while PCD can evolve by providing advantages to relatives. The synchronization of death between individuals suggests a group level property is being maintained and the mode of death also appears to have had an impact during the origin of multicellularity. PCD can result in the export of fitness from the cell to the group level via re-usable resources and PCD may also provide a mechanism for how groups beget new groups comprising kin. Furthermore, PCD is a means for solving a central problem of group living - the toxic effects of death - by making resources in dying cells beneficial to others. What emerges from the data reviewed here is that while PCD carries an obvious cost to the cell, it can be a driver of complexity in microbial communities.}, } @article {pmid27402737, year = {2016}, author = {Wahl, ME and Murray, AW}, title = {Multicellularity makes somatic differentiation evolutionarily stable.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {113}, number = {30}, pages = {8362-8367}, pmid = {27402737}, issn = {1091-6490}, support = {P50 GM068763/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; *Cell Differentiation ; Cell Division/genetics ; *Cell Lineage ; Cell Survival/genetics ; Genetic Engineering/methods ; Germ Cells/*cytology/metabolism ; *Models, Biological ; Mutation ; Saccharomyces cerevisiae/cytology/genetics ; }, abstract = {Many multicellular organisms produce two cell lineages: germ cells, whose descendants produce the next generation, and somatic cells, which support, protect, and disperse the germ cells. This germ-soma demarcation has evolved independently in dozens of multicellular taxa but is absent in unicellular species. A common explanation holds that in these organisms, inefficient intercellular nutrient exchange compels the fitness cost of producing nonreproductive somatic cells to outweigh any potential benefits. We propose instead that the absence of unicellular, soma-producing populations reflects their susceptibility to invasion by nondifferentiating mutants that ultimately eradicate the soma-producing lineage. We argue that multicellularity can prevent the victory of such mutants by giving germ cells preferential access to the benefits conferred by somatic cells. The absence of natural unicellular, soma-producing species previously prevented these hypotheses from being directly tested in vivo: to overcome this obstacle, we engineered strains of the budding yeast Saccharomyces cerevisiae that differ only in the presence or absence of multicellularity and somatic differentiation, permitting direct comparisons between organisms with different lifestyles. Our strains implement the essential features of irreversible conversion from germ line to soma, reproductive division of labor, and clonal multicellularity while maintaining sufficient generality to permit broad extension of our conclusions. Our somatic cells can provide fitness benefits that exceed the reproductive costs of their production, even in unicellular strains. We find that nondifferentiating mutants overtake unicellular populations but are outcompeted by multicellular, soma-producing strains, suggesting that multicellularity confers evolutionary stability to somatic differentiation.}, } @article {pmid27401232, year = {2016}, author = {Francois, CM and Duret, L and Simon, L and Mermillod-Blondin, F and Malard, F and Konecny-Dupré, L and Planel, R and Penel, S and Douady, CJ and Lefébure, T}, title = {No Evidence That Nitrogen Limitation Influences the Elemental Composition of Isopod Transcriptomes and Proteomes.}, journal = {Molecular biology and evolution}, volume = {33}, number = {10}, pages = {2605-2620}, doi = {10.1093/molbev/msw131}, pmid = {27401232}, issn = {1537-1719}, mesh = {Amino Acids/genetics/metabolism ; Animals ; Ecosystem ; Isopoda/*genetics/*metabolism ; Nitrogen/*deficiency/*metabolism ; Nucleotides/genetics/metabolism ; Phylogeny ; Proteome ; Selection, Genetic ; Transcriptome ; }, abstract = {The field of stoichiogenomics aims at understanding the influence of nutrient limitations on the elemental composition of the genome, transcriptome, and proteome. The 20 amino acids and the 4 nt differ in the number of nutrients they contain, such as nitrogen (N). Thus, N limitation shall theoretically select for changes in the composition of proteins or RNAs through preferential use of N-poor amino acids or nucleotides, which will decrease the N-budget of an organism. While these N-saving mechanisms have been evidenced in microorganisms, they remain controversial in multicellular eukaryotes. In this study, we used 13 surface and subterranean isopod species pairs that face strongly contrasted N limitations, either in terms of quantity or quality. We combined in situ nutrient quantification and transcriptome sequencing to test if N limitation selected for N-savings through changes in the expression and composition of the transcriptome and proteome. No evidence of N-savings was found in the total N-budget of transcriptomes or proteomes or in the average protein N-cost. Nevertheless, subterranean species evolving in N-depleted habitats displayed lower N-usage at their third codon positions. To test if this convergent compositional change was driven by natural selection, we developed a method to detect the strand-asymmetric signature that stoichiogenomic selection should leave in the substitution pattern. No such signature was evidenced, indicating that the observed stoichiogenomic-like patterns were attributable to nonadaptive processes. The absence of stoichiogenomic signal despite strong N limitation within a powerful phylogenetic framework casts doubt on the existence of stoichiogenomic mechanisms in metazoans.}, } @article {pmid27391808, year = {2016}, author = {Jeong, SY and Lee, JH and Shin, Y and Chung, S and Kuh, HJ}, title = {Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment.}, journal = {PloS one}, volume = {11}, number = {7}, pages = {e0159013}, pmid = {27391808}, issn = {1932-6203}, mesh = {Coculture Techniques/instrumentation/methods ; Collagen/*chemistry ; Colorectal Neoplasms/*metabolism/pathology ; Extracellular Matrix/chemistry ; Fibroblasts/*metabolism/pathology ; Humans ; *Lab-On-A-Chip Devices ; Spheroids, Cellular/*metabolism/pathology ; *Tumor Microenvironment ; }, abstract = {Multicellular 3D culture and interaction with stromal components are considered essential elements in establishing a 'more clinically relevant' tumor model. Matrix-embedded 3D cultures using a microfluidic chip platform can recapitulate the microscale interaction within tumor microenvironments. As a major component of tumor microenvironment, cancer-associated fibroblasts (CAFs) play a role in cancer progression and drug resistance. Here, we present a microfluidic chip-based tumor tissue culture model that integrates 3D tumor spheroids (TSs) with CAF in proximity within a hydrogel scaffold. HT-29 human colorectal carcinoma cells grew into 3D TSs and the growth was stimulated when co-cultured with fibroblasts as shown by 1.5-folds increase of % changes in diameter over 5 days. TS cultured for 6 days showed a reduced expression of Ki-67 along with increased expression of fibronectin when co-cultured with fibroblasts compared to mono-cultured TSs. Fibroblasts were activated under co-culture conditions, as demonstrated by increases in α-SMA expression and migratory activity. When exposed to paclitaxel, a survival advantage was observed in TSs co-cultured with activated fibroblasts. Overall, we demonstrated the reciprocal interaction between TSs and fibroblasts in our 7-channel microfluidic chip. The co-culture of 3D TS-CAF in a collagen matrix-incorporated microfluidic chip may be useful to study the tumor microenvironment and for evaluation of drug screening and evaluation.}, } @article {pmid27383475, year = {2016}, author = {Baek, SY and Jang, KH and Choi, EH and Ryu, SH and Kim, SK and Lee, JH and Lim, YJ and Lee, J and Jun, J and Kwak, M and Lee, YS and Hwang, JS and Venmathi Maran, BA and Chang, CY and Kim, IH and Hwang, UW}, title = {DNA Barcoding of Metazoan Zooplankton Copepods from South Korea.}, journal = {PloS one}, volume = {11}, number = {7}, pages = {e0157307}, pmid = {27383475}, issn = {1932-6203}, mesh = {Animals ; Copepoda/*genetics ; *DNA Barcoding, Taxonomic ; Electron Transport Complex IV/*genetics ; Genes, Mitochondrial ; Genetic Variation ; Geography ; Phylogeny ; Republic of Korea ; Sequence Analysis, DNA ; Species Specificity ; Zooplankton/*genetics ; }, abstract = {Copepods, small aquatic crustaceans, are the most abundant metazoan zooplankton and outnumber every other group of multicellular animals on earth. In spite of ecological and biological importance in aquatic environment, their morphological plasticity, originated from their various lifestyles and their incomparable capacity to adapt to a variety of environments, has made the identification of species challenging, even for expert taxonomists. Molecular approaches to species identification have allowed rapid detection, discrimination, and identification of cryptic or sibling species based on DNA sequence data. We examined sequence variation of a partial mitochondrial cytochrome C oxidase I gene (COI) from 133 copepod individuals collected from the Korean Peninsula, in order to identify and discriminate 94 copepod species covering six copepod orders of Calanoida, Cyclopoida, Harpacticoida, Monstrilloida, Poecilostomatoida and Siphonostomatoida. The results showed that there exists a clear gap with ca. 20 fold difference between the averages of within-specific sequence divergence (2.42%) and that of between-specific sequence divergence (42.79%) in COI, suggesting the plausible utility of this gene in delimitating copepod species. The results showed, with the COI barcoding data among 94 copepod species, that a copepod species could be distinguished from the others very clearly, only with four exceptions as followings: Mesocyclops dissimilis-Mesocyclops pehpeiensis (0.26% K2P distance in percent) and Oithona davisae-Oithona similis (1.1%) in Cyclopoida, Ostrincola japonica-Pseudomyicola spinosus (1.5%) in Poecilostomatoida, and Hatschekia japonica-Caligus quadratus (5.2%) in Siphonostomatoida. Thus, it strongly indicated that COI may be a useful tool in identifying various copepod species and make an initial progress toward the construction of a comprehensive DNA barcode database for copepods inhabiting the Korean Peninsula.}, } @article {pmid27382431, year = {2016}, author = {Zhang, S and Mercado-Uribe, I and Sood, A and Bast, RC and Liu, J}, title = {Coevolution of neoplastic epithelial cells and multilineage stroma via polyploid giant cells during immortalization and transformation of mullerian epithelial cells.}, journal = {Genes & cancer}, volume = {7}, number = {3-4}, pages = {60-72}, pmid = {27382431}, issn = {1947-6019}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; P50 CA083638/CA/NCI NIH HHS/United States ; }, abstract = {Stromal cells are generally considered to be derived primarily from the host's normal mesenchymal stromal cells or bone marrow. However, the origins of stromal cells have been quite controversial. To determine the role of polyploidy in tumor development, we examined the fate of normal mullerian epithelial cells during the immortalization and transformation process by tracing the expression of SV40 large T antigen. Here we show that immortalized or HRAS-transformed mullerian epithelial cells contain a subpopulation of polyploid giant cells that grow as multicellular spheroids expressing hematopoietic markers in response to treatment with CoCl2. The immortalized or transformed epithelial cells can transdifferentiate into stromal cells when transplanted into nude mice. Immunofluorescent staining revealed expression of stem cell factors OCT4, Nanog, and SOX-2 in spheroid, whereas expression of embryonic stem cell marker SSEA1 was increased in HRAS-transformed cells compared with their immortalized isogenic counterparts. These results suggest that normal mullerian epithelial cells are intrinsically highly plastic, via the formation of polyploid giant cells and activation of embryonic stem-like program, which work together to promote the coevolution of neoplastic epithelial cells and multiple lineage stromal cells.}, } @article {pmid27379901, year = {2016}, author = {Olson, BJ and Nedelcu, AM}, title = {Co-option during the evolution of multicellular and developmental complexity in the volvocine green algae.}, journal = {Current opinion in genetics & development}, volume = {39}, number = {}, pages = {107-115}, doi = {10.1016/j.gde.2016.06.003}, pmid = {27379901}, issn = {1879-0380}, mesh = {Cell Differentiation/*genetics ; Chlamydomonas/classification/genetics/growth & development ; Chlorophyta/classification/*genetics/growth & development ; *Evolution, Molecular ; Germ Cells/growth & development ; *Phylogeny ; Volvox/classification/genetics/growth & development ; }, abstract = {Despite its major impact on the evolution of Life on Earth, the transition to multicellularity remains poorly understood, especially in terms of its genetic basis. The volvocine algae are a group of closely related species that range in morphology from unicellular individuals (Chlamydomonas) to undifferentiated multicellular forms (Gonium) and complex organisms with distinct developmental programs and one (Pleodorina) or two (Volvox) specialized cell types. Modern genetic approaches, complemented by the recent sequencing of genomes from several key species, revealed that co-option of existing genes and pathways is the primary driving force for the evolution of multicellularity in this lineage. The initial transition to undifferentiated multicellularity, as typified by the extant Gonium, was driven primarily by the co-option of cell cycle regulation. Further morphological and developmental innovations in the lineage leading to Volvox resulted from additional co-option events involving genes important for embryonic inversion, asymmetric cell division, somatic and germ cell differentiation and the structure and function of the extracellular matrix. Because of their relatively low but variable levels of morphological and developmental complexity, simple underlying genetics and recent evolutionary history, the volvocine algae are providing significant insight into our understanding of the genetics and evolution of major developmental and morphological traits.}, } @article {pmid27376334, year = {2016}, author = {Bains, W and Schulze-Makuch, D}, title = {The Cosmic Zoo: The (Near) Inevitability of the Evolution of Complex, Macroscopic Life.}, journal = {Life (Basel, Switzerland)}, volume = {6}, number = {3}, pages = {}, pmid = {27376334}, issn = {2075-1729}, abstract = {Life on Earth provides a unique biological record from single-cell microbes to technologically intelligent life forms. Our evolution is marked by several major steps or innovations along a path of increasing complexity from microbes to space-faring humans. Here we identify various major key innovations, and use an analytical toolset consisting of a set of models to analyse how likely each key innovation is to occur. Our conclusion is that once the origin of life is accomplished, most of the key innovations can occur rather readily. The conclusion for other worlds is that if the origin of life can occur rather easily, we should live in a cosmic zoo, as the innovations necessary to lead to complex life will occur with high probability given sufficient time and habitat. On the other hand, if the origin of life is rare, then we might live in a rather empty universe.}, } @article {pmid27374341, year = {2016}, author = {Mikhailov, KV and Slyusarev, GS and Nikitin, MA and Logacheva, MD and Penin, AA and Aleoshin, VV and Panchin, YV}, title = {The Genome of Intoshia linei Affirms Orthonectids as Highly Simplified Spiralians.}, journal = {Current biology : CB}, volume = {26}, number = {13}, pages = {1768-1774}, doi = {10.1016/j.cub.2016.05.007}, pmid = {27374341}, issn = {1879-0445}, mesh = {Animals ; Female ; *Genome ; Host-Parasite Interactions ; Invertebrates/*classification/genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Orthonectids are rare parasites of marine invertebrates [1] that are commonly treated in textbooks as a taxon of uncertain affinity [2]. Trophic forms of orthonectids reside in the tissues of their hosts as multinucleated plasmodia, generating short-lived, worm-like ciliated female and male organisms that exit into the environment for copulation [3]. These ephemeral males and females are composed of just several hundred somatic cells and are deprived of digestive, circulatory, or excretory systems. Since their discovery in the 19(th) century, the orthonectids were described as organisms with no differentiated cell types and considered as part of Mesozoa, a putative link between multicellular animals and their unicellular relatives. More recently, this view was challenged as the new data suggested that orthonectids are animals that became simplified due to their parasitic way of life [3, 4]. Here, we report the genomic sequence of Intoshia linei, one of about 20 known species of orthonectids. The genomic data confirm recent morphological analysis asserting that orthonectids are members of Spiralia and possess muscular and nervous systems [5]. The 43-Mbp genome of I. linei encodes about 9,000 genes and retains those essential for the development and activity of muscular and nervous systems. The simplification of orthonectid body plan is associated with considerable reduction of metazoan developmental genes, leaving what might be viewed as the minimal gene set necessary to retain critical bilaterian features.}, } @article {pmid29368868, year = {2016}, author = {Zakharov, IA}, title = {[Horizontal gene transfer into the genomes of insects].}, journal = {Genetika}, volume = {52}, number = {7}, pages = {804-809}, pmid = {29368868}, issn = {0016-6758}, mesh = {Animals ; *Evolution, Molecular ; Gene Transfer, Horizontal/*physiology ; Insecta/*genetics ; }, abstract = {Horizontal gene transfer (HGT) is widespread in the world of prokaryotes, but the examples of this phenomenon among multicellular animals, particularly insects, are few. This review examines the transfer of genetic material to the nuclear genomes of insects from the mitochondrial genome (intracellular HGT), as well as from the genomes of viruses, bacteria, fungi, and unrelated insects. In most cases, the mechanisms of this transfer are unknown. Many pro- and eukaryotic genes that moved through the HGT are expressed in the insect genome and in some cases can provide the evolutionary innovations that are considered as aromorphoses.}, } @article {pmid27357338, year = {2016}, author = {Glöckner, G and Lawal, HM and Felder, M and Singh, R and Singer, G and Weijer, CJ and Schaap, P}, title = {The multicellularity genes of dictyostelid social amoebas.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {12085}, pmid = {27357338}, issn = {2041-1723}, support = {//Wellcome Trust/United Kingdom ; BB/G020426/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Cell Differentiation/genetics ; Dictyostelium/*genetics ; Gene Expression Profiling ; Gene Transfer, Horizontal ; *Genes, Essential ; Whole Genome Sequencing ; }, abstract = {The evolution of multicellularity enabled specialization of cells, but required novel signalling mechanisms for regulating cell differentiation. Early multicellular organisms are mostly extinct and the origins of these mechanisms are unknown. Here using comparative genome and transcriptome analysis across eight uni- and multicellular amoebozoan genomes, we find that 80% of proteins essential for the development of multicellular Dictyostelia are already present in their unicellular relatives. This set is enriched in cytosolic and nuclear proteins, and protein kinases. The remaining 20%, unique to Dictyostelia, mostly consists of extracellularly exposed and secreted proteins, with roles in sensing and recognition, while several genes for synthesis of signals that induce cell-type specialization were acquired by lateral gene transfer. Across Dictyostelia, changes in gene expression correspond more strongly with phenotypic innovation than changes in protein functional domains. We conclude that the transition to multicellularity required novel signals and sensors rather than novel signal processing mechanisms.}, } @article {pmid27356975, year = {2016}, author = {Yerramsetty, P and Stata, M and Siford, R and Sage, TL and Sage, RF and Wong, GK and Albert, VA and Berry, JO}, title = {Evolution of RLSB, a nuclear-encoded S1 domain RNA binding protein associated with post-transcriptional regulation of plastid-encoded rbcL mRNA in vascular plants.}, journal = {BMC evolutionary biology}, volume = {16}, number = {1}, pages = {141}, pmid = {27356975}, issn = {1471-2148}, mesh = {Chloroplasts/genetics ; *Evolution, Molecular ; *Gene Expression Regulation, Plant ; Magnoliopsida/*genetics ; Photosynthesis ; Phylogeny ; Plant Leaves/genetics ; Plant Proteins/*genetics/metabolism ; Plastids/*genetics/metabolism ; Poaceae/genetics ; RNA Processing, Post-Transcriptional ; RNA, Messenger/metabolism ; RNA-Binding Proteins/*genetics ; Ribulose-Bisphosphate Carboxylase/*genetics ; Zea mays/genetics ; }, abstract = {BACKGROUND: RLSB, an S-1 domain RNA binding protein of Arabidopsis, selectively binds rbcL mRNA and co-localizes with Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) within chloroplasts of C3 and C4 plants. Previous studies using both Arabidopsis (C3) and maize (C4) suggest RLSB homologs are post-transcriptional regulators of plastid-encoded rbcL mRNA. While RLSB accumulates in all Arabidopsis leaf chlorenchyma cells, in C4 leaves RLSB-like proteins accumulate only within Rubisco-containing bundle sheath chloroplasts of Kranz-type species, and only within central compartment chloroplasts in the single cell C4 plant Bienertia. Our recent evidence implicates this mRNA binding protein as a primary determinant of rbcL expression, cellular localization/compartmentalization, and photosynthetic function in all multicellular green plants. This study addresses the hypothesis that RLSB is a highly conserved Rubisco regulatory factor that occurs in the chloroplasts all higher plants.

RESULTS: Phylogenetic analysis has identified RLSB orthologs and paralogs in all major plant groups, from ancient liverworts to recent angiosperms. RLSB homologs were also identified in algae of the division Charophyta, a lineage closely related to land plants. RLSB-like sequences were not identified in any other algae, suggesting that it may be specific to the evolutionary line leading to land plants. The RLSB family occurs in single copy across most angiosperms, although a few species with two copies were identified, seemingly randomly distributed throughout the various taxa, although perhaps correlating in some cases with known ancient whole genome duplications. Monocots of the order Poales (Poaceae and Cyperaceae) were found to contain two copies, designated here as RLSB-a and RLSB-b, with only RLSB-a implicated in the regulation of rbcL across the maize developmental gradient. Analysis of microsynteny in angiosperms revealed high levels of conservation across eudicot species and for both paralogs in grasses, highlighting the possible importance of maintaining this gene and its surrounding genomic regions.

CONCLUSIONS: Findings presented here indicate that the RLSB family originated as a unique gene in land plant evolution, perhaps in the common ancestor of charophytes and higher plants. Purifying selection has maintained this as a highly conserved single- or two-copy gene across most extant species, with several conserved gene duplications. Together with previous findings, this study suggests that RLSB has been sustained as an important regulatory protein throughout the course of land plant evolution. While only RLSB-a has been directly implicated in rbcL regulation in maize, RLSB-b could have an overlapping function in the co-regulation of rbcL, or may have diverged as a regulator of one or more other plastid-encoded mRNAs. This analysis confirms that RLSB is an important and unique photosynthetic regulatory protein that has been continuously expressed in land plants as they emerged and diversified from their ancient common ancestor.}, } @article {pmid27355941, year = {2016}, author = {Stojković, S and Podolski-Renić, A and Dinić, J and Pavković, Ž and Ayuso, JM and Fernández, LJ and Ochoa, I and Pérez-García, VM and Pešić, V and Pešić, M}, title = {Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells-Characterization of a New in Vivo Model.}, journal = {Molecules (Basel, Switzerland)}, volume = {21}, number = {7}, pages = {}, pmid = {27355941}, issn = {1420-3049}, mesh = {Animals ; Antineoplastic Agents, Alkylating/*pharmacology ; Behavior, Animal/drug effects ; Brain Neoplasms/drug therapy/*genetics/*pathology ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; DNA Damage/*drug effects ; Disease Models, Animal ; *Drug Resistance, Neoplasm ; Glioma/drug therapy/*genetics/*pathology ; Humans ; Motor Activity/drug effects ; Neoplasm Invasiveness ; Rats ; }, abstract = {Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide (TMZ). Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells' invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats' behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells.}, } @article {pmid27339473, year = {2016}, author = {Chisholm, RH and Lorenzi, T and Clairambault, J}, title = {Cell population heterogeneity and evolution towards drug resistance in cancer: Biological and mathematical assessment, theoretical treatment optimisation.}, journal = {Biochimica et biophysica acta}, volume = {1860}, number = {11 Pt B}, pages = {2627-2645}, doi = {10.1016/j.bbagen.2016.06.009}, pmid = {27339473}, issn = {0006-3002}, mesh = {Drug Resistance, Neoplasm/*drug effects ; Humans ; Immunotherapy/methods ; Models, Biological ; Models, Theoretical ; Neoplasms/*drug therapy/*pathology ; Phenotype ; }, abstract = {BACKGROUND: Drug-induced drug resistance in cancer has been attributed to diverse biological mechanisms at the individual cell or cell population scale, relying on stochastically or epigenetically varying expression of phenotypes at the single cell level, and on the adaptability of tumours at the cell population level.

SCOPE OF REVIEW: We focus on intra-tumour heterogeneity, namely between-cell variability within cancer cell populations, to account for drug resistance. To shed light on such heterogeneity, we review evolutionary mechanisms that encompass the great evolution that has designed multicellular organisms, as well as smaller windows of evolution on the time scale of human disease. We also present mathematical models used to predict drug resistance in cancer and optimal control methods that can circumvent it in combined therapeutic strategies.

MAJOR CONCLUSIONS: Plasticity in cancer cells, i.e., partial reversal to a stem-like status in individual cells and resulting adaptability of cancer cell populations, may be viewed as backward evolution making cancer cell populations resistant to drug insult. This reversible plasticity is captured by mathematical models that incorporate between-cell heterogeneity through continuous phenotypic variables. Such models have the benefit of being compatible with optimal control methods for the design of optimised therapeutic protocols involving combinations of cytotoxic and cytostatic treatments with epigenetic drugs and immunotherapies.

GENERAL SIGNIFICANCE: Gathering knowledge from cancer and evolutionary biology with physiologically based mathematical models of cell population dynamics should provide oncologists with a rationale to design optimised therapeutic strategies to circumvent drug resistance, that still remains a major pitfall of cancer therapeutics. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.}, } @article {pmid27338490, year = {2016}, author = {Shapiro, JA}, title = {Nothing in Evolution Makes Sense Except in the Light of Genomics: Read-Write Genome Evolution as an Active Biological Process.}, journal = {Biology}, volume = {5}, number = {2}, pages = {}, pmid = {27338490}, issn = {2079-7737}, abstract = {The 21st century genomics-based analysis of evolutionary variation reveals a number of novel features impossible to predict when Dobzhansky and other evolutionary biologists formulated the neo-Darwinian Modern Synthesis in the middle of the last century. These include three distinct realms of cell evolution; symbiogenetic fusions forming eukaryotic cells with multiple genome compartments; horizontal organelle, virus and DNA transfers; functional organization of proteins as systems of interacting domains subject to rapid evolution by exon shuffling and exonization; distributed genome networks integrated by mobile repetitive regulatory signals; and regulation of multicellular development by non-coding lncRNAs containing repetitive sequence components. Rather than single gene traits, all phenotypes involve coordinated activity by multiple interacting cell molecules. Genomes contain abundant and functional repetitive components in addition to the unique coding sequences envisaged in the early days of molecular biology. Combinatorial coding, plus the biochemical abilities cells possess to rearrange DNA molecules, constitute a powerful toolbox for adaptive genome rewriting. That is, cells possess "Read-Write Genomes" they alter by numerous biochemical processes capable of rapidly restructuring cellular DNA molecules. Rather than viewing genome evolution as a series of accidental modifications, we can now study it as a complex biological process of active self-modification.}, } @article {pmid27330141, year = {2016}, author = {Xu, T and Qin, S and Hu, Y and Song, Z and Ying, J and Li, P and Dong, W and Zhao, F and Yang, H and Bao, Q}, title = {Whole genomic DNA sequencing and comparative genomic analysis of Arthrospira platensis: high genome plasticity and genetic diversity.}, journal = {DNA research : an international journal for rapid publication of reports on genes and genomes}, volume = {23}, number = {4}, pages = {325-338}, pmid = {27330141}, issn = {1756-1663}, mesh = {Evolution, Molecular ; Gene Transfer, Horizontal ; *Genome, Bacterial ; Genomic Instability ; Phylogeny ; *Polymorphism, Genetic ; Repetitive Sequences, Nucleic Acid ; Spirulina/classification/*genetics ; }, abstract = {Arthrospira platensis is a multi-cellular and filamentous non-N2-fixing cyanobacterium that is capable of performing oxygenic photosynthesis. In this study, we determined the nearly complete genome sequence of A. platensis YZ. A. platensis YZ genome is a single, circular chromosome of 6.62 Mb in size. Phylogenetic and comparative genomic analyses revealed that A. platensis YZ was more closely related to A. platensis NIES-39 than Arthrospira sp. PCC 8005 and A. platensis C1. Broad gene gains were identified between A. platensis YZ and three other Arthrospira speices, some of which have been previously demonstrated that can be laterally transferred among different species, such as restriction-modification systems-coding genes. Moreover, unprecedented extensive chromosomal rearrangements among different strains were observed. The chromosomal rearrangements, particularly the chromosomal inversions, were analysed and estimated to be closely related to palindromes that involved long inverted repeat sequences and the extensively distributed type IIR restriction enzyme in the Arthrospira genome. In addition, species from genus Arthrospira unanimously contained the highest rate of repetitive sequence compared with the other species of order Oscillatoriales, suggested that sequence duplication significantly contributed to Arthrospira genome phylogeny. These results provided in-depth views into the genomic phylogeny and structural variation of A. platensis, as well as provide a valuable resource for functional genomics studies.}, } @article {pmid27324572, year = {2016}, author = {Trojan, D and Schreiber, L and Bjerg, JT and Bøggild, A and Yang, T and Kjeldsen, KU and Schramm, A}, title = {A taxonomic framework for cable bacteria and proposal of the candidate genera Electrothrix and Electronema.}, journal = {Systematic and applied microbiology}, volume = {39}, number = {5}, pages = {297-306}, pmid = {27324572}, issn = {1618-0984}, support = {291650/ERC_/European Research Council/International ; }, mesh = {Aquatic Organisms/*classification/*genetics/isolation & purification ; Base Sequence ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Deltaproteobacteria/*classification/*genetics/isolation & purification ; Geologic Sediments/*microbiology ; In Situ Hybridization, Fluorescence ; Microscopy, Atomic Force ; Microscopy, Electron ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Cable bacteria are long, multicellular filaments that can conduct electric currents over centimeter-scale distances. All cable bacteria identified to date belong to the deltaproteobacterial family Desulfobulbaceae and have not been isolated in pure culture yet. Their taxonomic delineation and exact phylogeny is uncertain, as most studies so far have reported only short partial 16S rRNA sequences or have relied on identification by a combination of filament morphology and 16S rRNA-targeted fluorescence in situ hybridization with a Desulfobulbaceae-specific probe. In this study, nearly full-length 16S rRNA gene sequences of 16 individual cable bacteria filaments from freshwater, salt marsh, and marine sites of four geographic locations are presented. These sequences formed a distinct, monophyletic sister clade to the genus Desulfobulbus and could be divided into six coherent, species-level clusters, arranged as two genus-level groups. The same grouping was retrieved by phylogenetic analysis of full or partial dsrAB genes encoding the dissimilatory sulfite reductase. Based on these results, it is proposed to accommodate cable bacteria within two novel candidate genera: the mostly marine "Candidatus Electrothrix", with four candidate species, and the mostly freshwater "Candidatus Electronema", with two candidate species. This taxonomic framework can be used to assign environmental sequences confidently to the cable bacteria clade, even without morphological information. Database searches revealed 185 16S rRNA gene sequences that affiliated within the clade formed by the proposed cable bacteria genera, of which 120 sequences could be assigned to one of the six candidate species, while the remaining 65 sequences indicated the existence of up to five additional species.}, } @article {pmid27320726, year = {2016}, author = {Bao, W and Greenwold, MJ and Sawyer, RH}, title = {Expressed miRNAs target feather related mRNAs involved in cell signaling, cell adhesion and structure during chicken epidermal development.}, journal = {Gene}, volume = {591}, number = {2}, pages = {393-402}, pmid = {27320726}, issn = {1879-0038}, support = {P20 GM103499/GM/NIGMS NIH HHS/United States ; P20 RR016461/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; *Cell Adhesion ; Chickens ; Epidermal Cells ; Epidermis/growth & development/*metabolism ; Evolution, Molecular ; Feathers/*metabolism ; MicroRNAs/*metabolism ; RNA, Messenger/*metabolism ; *Signal Transduction ; Tenascin/metabolism ; Tissue Array Analysis ; }, abstract = {MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Previous studies have shown that miRNA regulation contributes to a diverse set of processes including cellular differentiation and morphogenesis which leads to the creation of different cell types in multicellular organisms and is thus key to animal development. Feathers are one of the most distinctive features of extant birds and are important for multiple functions including flight, thermal regulation, and sexual selection. However, the role of miRNAs in feather development has been woefully understudied despite the identification of cell signaling pathways, cell adhesion molecules and structural genes involved in feather development. In this study, we performed a microarray experiment comparing the expression of miRNAs and mRNAs among three embryonic stages of development and two tissues (scutate scale and feather) of the chicken. We combined this expression data with miRNA target prediction tools and a curated list of feather related genes to produce a set of 19 miRNA-mRNA duplexes. These targeted mRNAs have been previously identified as important cell signaling and cell adhesion genes as well as structural genes involved in feather and scale morphogenesis. Interestingly, the miRNA target site of the cell signaling pathway gene, Aldehyde Dehydrogenase 1 Family, Member A3 (ALDH1A3), is unique to birds indicating a novel role in Aves. The identified miRNA target site of the cell adhesion gene, Tenascin C (TNC), is only found in specific chicken TNC splice variants that are differentially expressed in developing scutate scale and feather tissue indicating an important role of miRNA regulation in epidermal differentiation. Additionally, we found that β-keratins, a major structural component of avian and reptilian epidermal appendages, are targeted by multiple miRNA genes. In conclusion, our work provides quantitative expression data on miRNAs and mRNAs during feather and scale development and has produced a highly diverse, but manageable list of miRNA-mRNA duplexes for future validation experiments.}, } @article {pmid27319135, year = {2016}, author = {Salasa, A and Mercadoc, MI and Zampini, IC and Ponessa, GI and Isla, MI}, title = {Determination of Botanical Origin of Propolis from Monte Region of Argentina by Histological and Chemical Methods.}, journal = {Natural product communications}, volume = {11}, number = {5}, pages = {627-630}, pmid = {27319135}, issn = {1934-578X}, mesh = {Argentina ; Fabaceae/*cytology ; Larrea/cytology ; Propolis/*analysis/chemistry ; }, abstract = {Propolis production by honey bees is the result of a selective harvest of exudates from plants in the neighborhood of the hive. This product is used in Argentina as a food supplement and alternative medicine. The aim of this study was to determine the botanical origin of propolis from the arid regions of Monte of Argentina using rapid histochemical techniques and by comparison of TLC and HPLC-DAD chromatographic profiles with extract profiles obtained from Zuccagnia punctata, Larrea divaricata and Larrea cuneifolia, plant species that grow in the study area as a natural community named "jarillal". Microscopical analysis revealed the presence of several Z. punctata structures, such as multicellular trichomes, leaflets, stems and young leaves. Remarkable was the richness of the propolis in two bioactive chalcones, also present in Z. punctata resin; these compounds can be regarded as possible markers for propolis identification and justify its use as a dietary supplement, functional food and medicinal product. This study indicates that the source of resin used by honey bees to produce propolis in the Monte region of Argentina is only Z. punctata, a native shrub widespread in this phytogeographical region, while other more abundant species (L. divaricata and L. cuneifolia) in the region were not found, indicating that this propolis could be defined as a mono-resin, type-Zuccagnia.}, } @article {pmid27318693, year = {2016}, author = {Hoffmeyer, TT and Burkhardt, P}, title = {Choanoflagellate models - Monosiga brevicollis and Salpingoeca rosetta.}, journal = {Current opinion in genetics & development}, volume = {39}, number = {}, pages = {42-47}, doi = {10.1016/j.gde.2016.05.016}, pmid = {27318693}, issn = {1879-0380}, mesh = {Animals ; Choanoflagellata/*genetics/growth & development ; *Evolution, Molecular ; Genome ; Models, Genetic ; *Phylogeny ; }, abstract = {Choanoflagellates are the closest single-celled relatives of animals and provide fascinating insights into developmental processes in animals. Two species, the choanoflagellates Monosiga brevicollis and Salpingoeca rosetta are emerging as promising model organisms to reveal the evolutionary origin of key animal innovations. In this review, we highlight how choanoflagellates are used to study the origin of multicellularity in animals. The newly available genomic resources and functional techniques provide important insights into the function of choanoflagellate pre- and postsynaptic proteins, cell-cell adhesion and signaling molecules and the evolution of animal filopodia and thus underscore the relevance of choanoflagellate models for evolutionary biology, neurobiology and cell biology research.}, } @article {pmid27318691, year = {2016}, author = {Adamska, M}, title = {Sponges as models to study emergence of complex animals.}, journal = {Current opinion in genetics & development}, volume = {39}, number = {}, pages = {21-28}, doi = {10.1016/j.gde.2016.05.026}, pmid = {27318691}, issn = {1879-0380}, mesh = {Animals ; *Evolution, Molecular ; Gene Regulatory Networks/*genetics ; Genome ; Germ Cells/*growth & development ; Porifera/anatomy & histology/*genetics/growth & development ; Stem Cells/metabolism ; }, abstract = {The emergence of complex animal life forms remains poorly understood despite substantial interest and research in this area. To be informative, the ideal models to study transitions from single-cell organisms to the first animals and then to mammalian-level complexity should be phylogenetically strategically placed and retain ancestral characters. Sponges (Porifera) are likely to be the earliest branching animal phylum. When analysed from morphological, genomic and developmental perspectives, sponges appear to combine features of single-cell eukaryotic organisms and the complex multicellular animals (Eumetazoa). Intriguingly, homologues of components of the eumetazoan regulatory networks specifying the endoderm, the germ-cells and stem cells and (neuro) sensory cells are expressed in sponge choanocytes, archaeocytes and larval sensory cells. Studies using sponges as model systems are already bringing insights into animal evolution, and have opened avenues to further research benefitting from the recent spectacular expansion of genomic technologies.}, } @article {pmid27318097, year = {2016}, author = {Schaap, P}, title = {Evolution of developmental signalling in Dictyostelid social amoebas.}, journal = {Current opinion in genetics & development}, volume = {39}, number = {}, pages = {29-34}, pmid = {27318097}, issn = {1879-0380}, support = {//Wellcome Trust/United Kingdom ; 100293/Z/12/Z//Wellcome Trust/United Kingdom ; BB/K000799/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Cyclic AMP/genetics ; Developmental Biology ; Dictyostelium/*genetics/growth & development ; *Evolution, Molecular ; *Phylogeny ; Signal Transduction/genetics ; Stress, Physiological/*genetics ; }, abstract = {Dictyostelia represent a tractable system to resolve the evolution of cell-type specialization, with some taxa differentiating into spores only, and other taxa with additionally one or up to four somatic cell types. One of the latter forms, Dictyostelium discoideum, is a popular model system for cell biology and developmental biology with key signalling pathways controlling cell-specialization being resolved recently. For the most dominant pathways, evolutionary origins were retraced to a stress response in the unicellular ancestor, while modifications in the ancestral pathway were associated with acquisition of multicellular complexity. This review summarizes our current understanding of developmental signalling in D. discoideum and its evolution.}, } @article {pmid27314399, year = {2016}, author = {Trosko, JE}, title = {Evolution of Microbial Quorum Sensing to Human Global Quorum Sensing: An Insight into How Gap Junctional Intercellular Communication Might Be Linked to the Global Metabolic Disease Crisis.}, journal = {Biology}, volume = {5}, number = {2}, pages = {}, pmid = {27314399}, issn = {2079-7737}, abstract = {The first anaerobic organism extracted energy for survival and reproduction from its source of nutrients, with the genetic means to ensure protection of its individual genome but also its species survival. While it had a means to communicate with its community via simple secreted molecules ("quorum sensing"), the eventual shift to an aerobic environment led to multi-cellular metazoan organisms, with evolutionary-selected genes to form extracellular matrices, stem cells, stem cell niches, and a family of gap junction or "connexin" genes. These germinal and somatic stem cells responded to extracellular signals that triggered intra-cellular signaling to regulate specific genes out of the total genome. These extra-cellular induced intra-cellular signals also modulated gap junctional intercellular communication (GJIC) in order to regulate the new cellular functions of symmetrical and asymmetrical cell division, cell differentiation, modes of cell death, and senescence. Within the hierarchical and cybernetic concepts, differentiated by neurons organized in the brain of the Homo sapiens, the conscious mind led to language, abstract ideas, technology, myth-making, scientific reasoning, and moral decision-making, i.e., the creation of culture. Over thousands of years, this has created the current collision between biological and cultural evolution, leading to the global "metabolic disease" crisis.}, } @article {pmid27307998, year = {2016}, author = {Miyanishi, H and Inokuchi, M and Nobata, S and Kaneko, T}, title = {Past seawater experience enhances seawater adaptability in medaka, Oryzias latipes.}, journal = {Zoological letters}, volume = {2}, number = {}, pages = {12}, pmid = {27307998}, issn = {2056-306X}, abstract = {BACKGROUND: During the course of evolution, fishes have acquired adaptability to various salinity environments, and acquirement of seawater (SW) adaptability has played important roles in fish evolution and diversity. However, little is known about how saline environments influence the acquirement of SW adaptability. The Japanese medaka Oryzias latipes is a euryhaline species that usually inhabits freshwater (FW), but is also adaptable to full-strength SW when transferred through diluted SW. In the present study, we examined how past SW experience affects hyposmoregulatory ability in Japanese medaka.

RESULTS: For the preparation of SW-experienced fish, FW medaka were acclimated to SW after pre-acclimation to 1/2 SW, and the SW-acclimated fish were transferred back to FW. The SW-experienced fish and control FW fish (SW-inexperienced fish) were transferred directly to SW. Whereas control FW fish did not survive direct transfer to SW, 1/4 of SW-experienced fish adapted successfully to SW. Although there were no significant differences in blood osmolality and plasma Na(+) and Cl(-) concentrations between SW-experienced and control FW medaka in FW, increments in these parameters following SW transfer were lower in SW-experienced fish than in control FW fish. The gene expression of SW-type Na(+), K(+)-ATPase (NKA) in the gills of SW-experienced medaka increased more quickly after direct SW transfer compared with the expression in control FW fish. Prior to SW transfer, the density of NKA-immunoreactive ionocytes in the gills was higher in SW-experienced fish than in control FW fish. Ionocytes expressing CFTR Cl(-) channel at the apical membrane and those forming multicellular complexes, both of which were characteristic of SW-type ionocytes, were also increased in SW-experienced fish.

CONCLUSION: These results indicate that past SW experience enhances the capacity of Na(+) and Cl(-) secretion in ionocytes and thus hypoosmoregulatory ability of Japanese medaka, suggesting the presence of epigenetic mechanisms involved in seawater adaptation.}, } @article {pmid27300174, year = {2016}, author = {De Felici, M}, title = {The Formation and Migration of Primordial Germ Cells in Mouse and Man.}, journal = {Results and problems in cell differentiation}, volume = {58}, number = {}, pages = {23-46}, doi = {10.1007/978-3-319-31973-5_2}, pmid = {27300174}, issn = {0080-1844}, mesh = {Animals ; Epigenesis, Genetic ; Female ; Germ Cells/*cytology ; Gonads/cytology/*growth & development ; Humans ; Male ; Meiosis ; Mice ; Ovary/cytology ; Testis/cytology ; }, abstract = {In most multicellular organisms, including mammals, germ cells are at the origin of new organisms and ensure the continuation of the genetic and epigenetic information across the generations.In the mammalian germ line, the primordial germ cells (PGCs) are the precursors of the primary oocytes and prospermatogonia of fetal ovaries and testes, respectively. In mammals such as the primates, in which the formation of the primary oocytes is largely asynchronous and occurs during a relatively long period, PGCs after the arrival into the XX gonadal ridges are termed oogonia which then become primary oocytes when entering into meiotic prophase I. In the fetal testes, germ cells derived from the PGCs after gonad colonization are termed prospermatogonia or gonocytes.One of the most fascinating aspect of the mammalian germline development is that it is probably the first cell lineage to be established in the embryo by epigenetic mechanisms and that these inductive events happen in extraembryonic tissues much earlier that gonad develop inside the embryo proper. Moreover, such events prepare the germ cells for totipotency through genetic and epigenetic regulations of their genome function. How this occurs remained a mystery until short time ago.In this chapter, I will report and discuss the most recent advances in the cellular and molecular mechanisms underlying the formation in extraembryonic tissues and migration of PGCs toward the gonadal ridges made primarily by studies carried out in the mouse with some perspective in the human. Established concepts about these processes will be only summarized when necessary since they are widely described and discussed in many excellent reviews; most of them are cited in the text below.}, } @article {pmid27298474, year = {2016}, author = {Foley, RA}, title = {Mosaic evolution and the pattern of transitions in the hominin lineage.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1698}, pages = {}, pmid = {27298474}, issn = {1471-2970}, mesh = {*Adaptation, Biological ; Animals ; *Biological Evolution ; Fossils/*anatomy & histology ; Hominidae/*anatomy & histology ; Humans ; }, abstract = {Humans are uniquely unique, in terms of the extreme differences between them and other living organisms, and the impact they are having on the biosphere. The evolution of humans can be seen, as has been proposed, as one of the major transitions in evolution, on a par with the origins of multicellular organisms or the eukaryotic cell (Maynard Smith & Szathmáry 1997 Major transitions in evolution). Major transitions require the evolution of greater complexity and the emergence of new evolutionary levels or processes. Does human evolution meet these conditions? I explore the diversity of evidence on the nature of transitions in human evolution. Four levels of transition are proposed-baseline, novel taxa, novel adaptive zones and major transitions-and the pattern of human evolution considered in the light of these. The primary conclusions are that changes in human evolution occur continuously and cumulatively; that novel taxa and the appearance of new adaptations are not clustered very tightly in particular periods, although there are three broad transitional phases (Pliocene, Plio-Pleistocene and later Quaternary). Each phase is distinctive, with the first based on ranging and energetics, the second on technology and niche expansion, and the third on cognition and cultural processes. I discuss whether this constitutes a 'major transition' in the context of the evolutionary processes more broadly; the role of behaviour in evolution; and the opportunity provided by the rich genetic, phenotypic (fossil morphology) and behavioural (archaeological) record to examine in detail major transitions and the microevolutionary patterns underlying macroevolutionary change. It is suggested that the evolution of the hominin lineage is consistent with a mosaic pattern of change.This article is part of the themed issue 'Major transitions in human evolution'.}, } @article {pmid27282029, year = {2016}, author = {Félix, MA}, title = {Phenotypic Evolution With and Beyond Genome Evolution.}, journal = {Current topics in developmental biology}, volume = {119}, number = {}, pages = {291-347}, doi = {10.1016/bs.ctdb.2016.04.002}, pmid = {27282029}, issn = {1557-8933}, mesh = {Animals ; *Biological Evolution ; Cell Cycle ; DNA ; Environment ; Genes ; Genetic Association Studies ; *Genetic Variation ; *Genome ; Genotype ; Phenotype ; Selection, Genetic ; }, abstract = {DNA does not make phenotypes on its own. In this volume entitled "Genes and Phenotypic Evolution," the present review draws the attention on the process of phenotype construction-including development of multicellular organisms-and the multiple interactions and feedbacks between DNA, organism, and environment at various levels and timescales in the evolutionary process. First, during the construction of an individual's phenotype, DNA is recruited as a template for building blocks within the cellular context and may in addition be involved in dynamical feedback loops that depend on the environmental and organismal context. Second, in the production of phenotypic variation among individuals, stochastic, environmental, genetic, and parental sources of variation act jointly. While in controlled laboratory settings, various genetic and environmental factors can be tested one at a time or in various combinations, they cannot be separated in natural populations because the environment is not controlled and the genotype can rarely be replicated. Third, along generations, genotype and environment each have specific properties concerning the origin of their variation, the hereditary transmission of this variation, and the evolutionary feedbacks. Natural selection acts as a feedback from phenotype and environment to genotype. This review integrates recent results and concrete examples that illustrate these three points. Although some themes are shared with recent calls and claims to a new conceptual framework in evolutionary biology, the viewpoint presented here only means to add flesh to the standard evolutionary synthesis.}, } @article {pmid27273532, year = {2016}, author = {West, JA and Zuccarello, GC and de Goër, SL and Stavrias, LA and Verbruggen, H}, title = {Rhodenigma contortum, an obscure new genus and species of Rhodogorgonales (Rhodophyta) from Western Australia.}, journal = {Journal of phycology}, volume = {52}, number = {3}, pages = {397-403}, doi = {10.1111/jpy.12402}, pmid = {27273532}, issn = {1529-8817}, mesh = {Algal Proteins/genetics/metabolism ; Phylogeny ; RNA, Algal/genetics/metabolism ; Rhodophyta/*anatomy & histology/*classification/genetics ; Sequence Analysis, DNA ; Western Australia ; }, abstract = {An unknown microscopic, branched filamentous red alga was isolated into culture from coral fragments collected in Coral Bay, Western Australia. It grew well unattached or attached to glass with no reproduction other than fragmentation of filaments. Cells of some branch tips became slightly contorted and digitated, possibly as a substrate-contact-response seen at filament tips of various algae. Attached multicellular compact disks on glass had a very different cellular configuration and size than the free filaments. In culture the filaments did not grow on or in coral fragments. Molecular phylogenies based on four markers (rbcL, cox1, 18S, 28S) clearly showed it belongs to the order Rhodogorgonales, as a sister clade of Renouxia. Based on these results, the alga is described as the new genus and species Rhodenigma contortum in the Rhodogorgonaceae. It had no morphological similarity to either of the other genera in Rhodogorgonaceae and illustrates the unknown diversity in cryptic habitats such as tropical coral rubble.}, } @article {pmid27271841, year = {2016}, author = {Greischar, MA and Mideo, N and Read, AF and Bjørnstad, ON}, title = {Predicting optimal transmission investment in malaria parasites.}, journal = {Evolution; international journal of organic evolution}, volume = {70}, number = {7}, pages = {1542-1558}, pmid = {27271841}, issn = {1558-5646}, support = {R01 GM089932/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Culicidae/*parasitology ; Genetic Fitness ; *Host-Parasite Interactions ; Malaria/*transmission ; Models, Biological ; Plasmodium/genetics/*physiology ; Population Dynamics ; Reproduction ; }, abstract = {In vertebrate hosts, malaria parasites face a tradeoff between replicating and the production of transmission stages that can be passed onto mosquitoes. This tradeoff is analogous to growth-reproduction tradeoffs in multicellular organisms. We use a mathematical model tailored to the life cycle and dynamics of malaria parasites to identify allocation strategies that maximize cumulative transmission potential to mosquitoes. We show that plastic strategies can substantially outperform fixed allocation because parasites can achieve greater fitness by investing in proliferation early and delaying the production of transmission stages. Parasites should further benefit from restraining transmission investment later in infection, because such a strategy can help maintain parasite numbers in the face of resource depletion. Early allocation decisions are predicted to have the greatest impact on parasite fitness. If the immune response saturates as parasite numbers increase, parasites should benefit from even longer delays prior to transmission investment. The presence of a competing strain selects for consistently lower levels of transmission investment and dramatically increased exploitation of the red blood cell resource. While we provide a detailed analysis of tradeoffs pertaining to malaria life history, our approach for identifying optimal plastic allocation strategies may be broadly applicable.}, } @article {pmid27265398, year = {2016}, author = {Breuninger, H and Thamm, A and Streubel, S and Sakayama, H and Nishiyama, T and Dolan, L}, title = {Diversification of a Transcription Factor Family Led to the Evolution of Antagonistically Acting Genetic Regulators of Root Hair Growth.}, journal = {Current biology : CB}, volume = {26}, number = {12}, pages = {1622-1628}, pmid = {27265398}, issn = {1879-0445}, mesh = {Basic Helix-Loop-Helix Transcription Factors/*genetics ; *Evolution, Molecular ; Gene Duplication ; Gene Expression ; *Gene Regulatory Networks ; Multigene Family ; Plant Development/*genetics ; Plant Roots/growth & development ; Plants/*genetics ; }, abstract = {Streptophytes colonized the land some time before 470 million years ago [1-3]. The colonization coincided with an increase in morphological and cellular diversity [4-7]. This increase in diversity is correlated with a proliferation in transcription factors encoded in genomes [8-10]. This suggests that gene duplication and subsequent diversification of function was instrumental in the generation of land plant diversity. Here, we investigate the diversification of the streptophyte-specific Lotus japonicus ROOTHAIRLESS LIKE (LRL) transcription factor (TF) [11, 12] subfamily of basic loop helix (bHLH) proteins by comparing gene function in early divergent and derived land plant species. We report that the single Marchantia polymorpha LRL gene acts as a general growth regulator required for rhizoid development, a function that has been partially conserved throughout multicellular streptophytes. In contrast, the five relatively derived Arabidopsis thaliana LRL genes comprise two antagonistically acting groups of differentially expressed genes. The diversification of LRL genes accompanied the evolution of an antagonistic regulatory element controlling root hair development.}, } @article {pmid27263360, year = {2016}, author = {Weissenbach, J}, title = {The rise of genomics.}, journal = {Comptes rendus biologies}, volume = {339}, number = {7-8}, pages = {231-239}, doi = {10.1016/j.crvi.2016.05.002}, pmid = {27263360}, issn = {1768-3238}, mesh = {Animals ; Computational Biology ; DNA/genetics ; Evolution, Molecular ; Genome ; Genomics/*history ; History, 20th Century ; History, 21st Century ; Humans ; }, abstract = {A brief history of the development of genomics is provided. Complete sequencing of genomes of uni- and multicellular organisms is based on important progress in sequencing and bioinformatics. Evolution of these methods is ongoing and has triggered an explosion in data production and analysis. Initial analyses focused on the inventory of genes encoding proteins. Completeness and quality of gene prediction remains crucial. Genome analyses profoundly modified our views on evolution, biodiversity and contributed to the detection of new functions, yet to be fully elucidated, such as those fulfilled by non-coding RNAs. Genomics has become the basis for the study of biology and provides the molecular support for a bunch of large-scale studies, the omics.}, } @article {pmid27252218, year = {2016}, author = {Colley, NJ and Nilsson, DE}, title = {Photoreception in Phytoplankton.}, journal = {Integrative and comparative biology}, volume = {56}, number = {5}, pages = {764-775}, pmid = {27252218}, issn = {1557-7023}, support = {P30 EY016665/EY/NEI NIH HHS/United States ; R01 EY008768/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Light ; Locomotion ; Phytoplankton/*physiology ; Ultraviolet Rays ; }, abstract = {In many species of phytoplankton, simple photoreceptors monitor ambient lighting. Photoreceptors provide a number of selective advantages including the ability to assess the time of day for circadian rhythms, seasonal changes, and the detection of excessive light intensities and harmful UV light. Photoreceptors also serve as depth gauges in the water column for behaviors such as diurnal vertical migration. Photoreceptors can be organized together with screening pigment into visible eyespots. In a wide variety of motile phytoplankton, including Chlamydomonas, Volvox, Euglena, and Kryptoperidinium, eyespots are light-sensitive organelles residing within the cell. Eyespots are composed of photoreceptor proteins and typically red to orange carotenoid screening pigments. This association of photosensory pigment with screening pigment allows for detection of light directionality, needed for light-guided behaviors such as positive and negative phototaxis. In Chlamydomonas, the eyespot is located in the chloroplast and Chlamydomonas expresses a number of photosensory pigments including the microbial channelrhodopsins (ChR1 and ChR2). Dinoflagellates are unicellular protists that are ecologically important constituents of the phytoplankton. They display a great deal of diversity in morphology, nutritional modes and symbioses, and can be photosynthetic or heterotrophic, feeding on smaller phytoplankton. Dinoflagellates, such as Kryptoperidinium foliaceum, have eyespots that are used for light-mediated tasks including phototaxis. Dinoflagellates belonging to the family Warnowiaceae have a more elaborate eye. Their eye-organelle, called an ocelloid, is a large, elaborate structure consisting of a focusing lens, highly ordered retinal membranes, and a shield of dark pigment. This complex eye-organelle is similar to multicellular camera eyes, such as our own. Unraveling the molecular makeup, structure and function of dinoflagellate eyes, as well as light-guided behaviors in phytoplankton can inform us about the selective forces that drove evolution in the important steps from light detection to vision. We show here that the evolution from simple photoreception to vision seems to have independently followed identical paths and principles in phytoplankton and animals, significantly strengthening our understanding of this important biological process.}, } @article {pmid27250874, year = {2016}, author = {Horst, NA and Katz, A and Pereman, I and Decker, EL and Ohad, N and Reski, R}, title = {A single homeobox gene triggers phase transition, embryogenesis and asexual reproduction.}, journal = {Nature plants}, volume = {2}, number = {}, pages = {15209}, doi = {10.1038/nplants.2015.209}, pmid = {27250874}, issn = {2055-0278}, mesh = {Bryopsida/embryology/*genetics/physiology ; Diploidy ; Genes, Homeobox/*genetics ; Germ Cells, Plant/physiology ; Haploidy ; Reproduction, Asexual ; }, abstract = {Plants characteristically alternate between haploid gametophytic and diploid sporophytic stages. Meiosis and fertilization respectively initiate these two different ontogenies(1). Genes triggering ectopic embryo development on vegetative sporophytic tissues are well described(2,3); however, a genetic control of embryo development from gametophytic tissues remains elusive. Here, in the moss Physcomitrella patens we show that ectopic overexpression of the homeobox gene BELL1 induces embryo formation and subsequently reproductive diploid sporophytes from specific gametophytic cells without fertilization. In line with this, BELL1 loss-of-function mutants have a wild-type phenotype, except that their egg cells are bigger and unable to form embryos. Our results identify BELL1 as a master regulator for the gametophyte-to-sporophyte transition in P. patens and provide mechanistic insights into the evolution of embryos that can generate multicellular diploid sporophytes. This developmental innovation facilitated the colonization of land by plants about 500 million years ago(4) and thus shaped our current ecosystems.}, } @article {pmid27248802, year = {2016}, author = {Howe, K and Schiffer, PH and Zielinski, J and Wiehe, T and Laird, GK and Marioni, JC and Soylemez, O and Kondrashov, F and Leptin, M}, title = {Structure and evolutionary history of a large family of NLR proteins in the zebrafish.}, journal = {Open biology}, volume = {6}, number = {4}, pages = {160009}, pmid = {27248802}, issn = {2046-2441}, support = {335980/ERC_/European Research Council/International ; HG002659/HG/NHGRI NIH HHS/United States ; 55007424//Howard Hughes Medical Institute/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; Conserved Sequence ; *Evolution, Molecular ; Genome ; Multigene Family ; NLR Proteins/*chemistry/*genetics ; Protein Domains ; Time Factors ; Zebrafish/genetics/*metabolism ; Zebrafish Proteins/*chemistry/*genetics ; }, abstract = {Multicellular eukaryotes have evolved a range of mechanisms for immune recognition. A widespread family involved in innate immunity are the NACHT-domain and leucine-rich-repeat-containing (NLR) proteins. Mammals have small numbers of NLR proteins, whereas in some species, mostly those without adaptive immune systems, NLRs have expanded into very large families. We describe a family of nearly 400 NLR proteins encoded in the zebrafish genome. The proteins share a defining overall structure, which arose in fishes after a fusion of the core NLR domains with a B30.2 domain, but can be subdivided into four groups based on their NACHT domains. Gene conversion acting differentially on the NACHT and B30.2 domains has shaped the family and created the groups. Evidence of positive selection in the B30.2 domain indicates that this domain rather than the leucine-rich repeats acts as the pathogen recognition module. In an unusual chromosomal organization, the majority of the genes are located on one chromosome arm, interspersed with other large multigene families, including a new family encoding zinc-finger proteins. The NLR-B30.2 proteins represent a new family with diversity in the specific recognition module that is present in fishes in spite of the parallel existence of an adaptive immune system.}, } @article {pmid27242148, year = {2016}, author = {Nowicka, B and Kruk, J}, title = {Powered by light: Phototrophy and photosynthesis in prokaryotes and its evolution.}, journal = {Microbiological research}, volume = {186-187}, number = {}, pages = {99-118}, doi = {10.1016/j.micres.2016.04.001}, pmid = {27242148}, issn = {1618-0623}, mesh = {Bacteria/genetics/*metabolism ; *Biological Evolution ; Carbon Dioxide/metabolism ; *Light ; Oxygen/metabolism ; *Photosynthesis ; *Phototrophic Processes ; }, abstract = {Photosynthesis is a complex metabolic process enabling photosynthetic organisms to use solar energy for the reduction of carbon dioxide into biomass. This ancient pathway has revolutionized life on Earth. The most important event was the development of oxygenic photosynthesis. It had a tremendous impact on the Earth's geochemistry and the evolution of living beings, as the rise of atmospheric molecular oxygen enabled the development of a highly efficient aerobic metabolism, which later led to the evolution of complex multicellular organisms. The mechanism of photosynthesis has been the subject of intensive research and a great body of data has been accumulated. However, the evolution of this process is not fully understood, and the development of photosynthesis in prokaryota in particular remains an unresolved question. This review is devoted to the occurrence and main features of phototrophy and photosynthesis in prokaryotes. Hypotheses concerning the origin and spread of photosynthetic traits in bacteria are also discussed.}, } @article {pmid27226324, year = {2016}, author = {Hunter, GL and Hadjivasiliou, Z and Bonin, H and He, L and Perrimon, N and Charras, G and Baum, B}, title = {Coordinated control of Notch/Delta signalling and cell cycle progression drives lateral inhibition-mediated tissue patterning.}, journal = {Development (Cambridge, England)}, volume = {143}, number = {13}, pages = {2305-2310}, pmid = {27226324}, issn = {1477-9129}, support = {BB/K009001/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; P40 OD018537/OD/NIH HHS/United States ; BB/J008532/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; *Body Patterning ; *Cell Cycle ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/cytology/*embryology/*metabolism ; Epithelial Cells/cytology/metabolism ; Intracellular Signaling Peptides and Proteins/*metabolism ; Membrane Proteins/*metabolism ; Receptors, Notch/*metabolism ; Sense Organs/cytology ; *Signal Transduction ; Stem Cells/cytology/metabolism ; Time Factors ; Vibrissae/cytology/embryology ; }, abstract = {Coordinating cell differentiation with cell growth and division is crucial for the successful development, homeostasis and regeneration of multicellular tissues. Here, we use bristle patterning in the fly notum as a model system to explore the regulatory and functional coupling of cell cycle progression and cell fate decision-making. The pattern of bristles and intervening epithelial cells (ECs) becomes established through Notch-mediated lateral inhibition during G2 phase of the cell cycle, as neighbouring cells physically interact with each other via lateral contacts and/or basal protrusions. Since Notch signalling controls cell division timing downstream of Cdc25, ECs in lateral contact with a Delta-expressing cell experience higher levels of Notch signalling and divide first, followed by more distant neighbours, and lastly Delta-expressing cells. Conversely, mitotic entry and cell division makes ECs refractory to lateral inhibition signalling, fixing their fate. Using a combination of experiments and computational modelling, we show that this reciprocal relationship between Notch signalling and cell cycle progression acts like a developmental clock, providing a delimited window of time during which cells decide their fate, ensuring efficient and orderly bristle patterning.}, } @article {pmid27221222, year = {2016}, author = {Steed, E and Faggianelli, N and Roth, S and Ramspacher, C and Concordet, JP and Vermot, J}, title = {klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {11646}, pmid = {27221222}, issn = {2041-1723}, mesh = {Animals ; Animals, Genetically Modified ; Extracellular Matrix/metabolism ; Fibronectins/*metabolism ; Gene Expression Profiling ; Heart Valves/*embryology ; Kruppel-Like Transcription Factors/*metabolism ; *Mechanotransduction, Cellular ; Zebrafish ; Zebrafish Proteins/*metabolism ; }, abstract = {The heartbeat and blood flow signal to endocardial cell progenitors through mechanosensitive proteins that modulate the genetic program controlling heart valve morphogenesis. To date, the mechanism by which mechanical forces coordinate tissue morphogenesis is poorly understood. Here we use high-resolution imaging to uncover the coordinated cell behaviours leading to heart valve formation. We find that heart valves originate from progenitors located in the ventricle and atrium that generate the valve leaflets through a coordinated set of endocardial tissue movements. Gene profiling analyses and live imaging reveal that this reorganization is dependent on extracellular matrix proteins, in particular on the expression of fibronectin1b. We show that blood flow and klf2a, a major endocardial flow-responsive gene, control these cell behaviours and fibronectin1b synthesis. Our results uncover a unique multicellular layering process leading to leaflet formation and demonstrate that endocardial mechanotransduction and valve morphogenesis are coupled via cellular rearrangements mediated by fibronectin synthesis.}, } @article {pmid27213462, year = {2016}, author = {Miller, WB}, title = {Cognition, Information Fields and Hologenomic Entanglement: Evolution in Light and Shadow.}, journal = {Biology}, volume = {5}, number = {2}, pages = {}, pmid = {27213462}, issn = {2079-7737}, abstract = {As the prime unification of Darwinism and genetics, the Modern Synthesis continues to epitomize mainstay evolutionary theory. Many decades after its formulation, its anchor assumptions remain fixed: conflict between macro organic organisms and selection at that level represent the near totality of any evolutionary narrative. However, intervening research has revealed a less easily appraised cellular and microbial focus for eukaryotic existence. It is now established that all multicellular eukaryotic organisms are holobionts representing complex collaborations between the co-aligned microbiome of each eukaryote and its innate cells into extensive mixed cellular ecologies. Each of these ecological constituents has demonstrated faculties consistent with basal cognition. Consequently, an alternative hologenomic entanglement model is proposed with cognition at its center and conceptualized as Pervasive Information Fields within a quantum framework. Evolutionary development can then be reconsidered as being continuously based upon communication between self-referential constituencies reiterated at every scope and scale. Immunological reactions support and reinforce self-recognition juxtaposed against external environmental stresses.}, } @article {pmid27208723, year = {2017}, author = {Kim, HY and Jackson, TR and Davidson, LA}, title = {On the role of mechanics in driving mesenchymal-to-epithelial transitions.}, journal = {Seminars in cell & developmental biology}, volume = {67}, number = {}, pages = {113-122}, pmid = {27208723}, issn = {1096-3634}, support = {R01 HD044750/HD/NICHD NIH HHS/United States ; T32 HL076124/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Biomechanical Phenomena ; Cadherins/genetics/metabolism ; Cell Division ; Cell Polarity ; Cellular Reprogramming/genetics ; Drosophila melanogaster/*genetics/growth & development/metabolism ; Embryo, Mammalian ; Embryo, Nonmammalian ; Epithelial Cells/cytology/*metabolism ; Epithelial-Mesenchymal Transition/*genetics ; Extracellular Matrix/chemistry/metabolism ; Humans ; *Mechanotransduction, Cellular ; Mesenchymal Stem Cells/cytology/*metabolism ; Morphogenesis/*genetics ; Vimentin/genetics/metabolism ; }, abstract = {The mesenchymal-to-epithelial transition (MET) is an intrinsically mechanical process describing a multi-step progression where autonomous mesenchymal cells gradually become tightly linked, polarized epithelial cells. METs are fundamental to a wide range of biological processes, including the evolution of multicellular organisms, generation of primary and secondary epithelia during development and organogenesis, and the progression of diseases including cancer. In these cases, there is an interplay between the establishment of cell polarity and the mechanics of neighboring cells and microenvironment. In this review, we highlight a spectrum of METs found in normal development as well as in pathological lesions, and provide insight into the critical role mechanics play at each step. We define MET as an independent process, distinct from a reverse-EMT, and propose questions to further explore the cellular and physical mechanisms of MET.}, } @article {pmid27200293, year = {2016}, author = {Palma, A and Grande, S and Luciani, AM and Mlynárik, V and Guidoni, L and Viti, V and Rosi, A}, title = {Metabolic Study of Breast MCF-7 Tumor Spheroids after Gamma Irradiation by (1)H NMR Spectroscopy and Microimaging.}, journal = {Frontiers in oncology}, volume = {6}, number = {}, pages = {105}, pmid = {27200293}, issn = {2234-943X}, abstract = {Multicellular tumor spheroids are an important model system to investigate the response of tumor cells to radio- and chemotherapy. They share more properties with the original tumor than cells cultured as 2D monolayers do, which helps distinguish the intrinsic properties of monolayer cells from those induced during cell aggregation in 3D spheroids. The paper investigates some metabolic aspects of small tumor spheroids of breast cancer and their originating MCF-7 cells, grown as monolayer, by means of high-resolution (HR) (1)H NMR spectroscopy and MR microimaging before and after gamma irradiation. The spectra of spheroids were characterized by higher intensity of mobile lipids, mostly neutral lipids, and glutamine (Gln) signals with respect to their monolayer cells counterpart, mainly owing to the lower oxygen supply in spheroids. Morphological changes of small spheroids after gamma-ray irradiation, such as loss of their regular shape, were observed by MR microimaging. Lipid signal intensity increased after irradiation, as evidenced in both MR localized spectra of the single spheroid and in HR NMR spectra of spheroid suspensions. Furthermore, the intense Gln signal from spectra of irradiated spheroids remained unchanged, while the low Gln signal observed in monolayer cells increased after irradiation. Similar results were observed in cells grown in hypoxic conditions. The different behavior of Gln in 2D monolayers and in 3D spheroids supports the hypothesis that a lower oxygen supply induces both an upregulation of Gln synthetase and a downregulation of glutaminases with the consequent increase in Gln content, as already observed under hypoxic conditions. The data herein indicate that (1)H NMR spectroscopy can be a useful tool for monitoring cell response to different constraints. The use of spheroid suspensions seems to be a feasible alternative to localized spectroscopy since similar effects were found after radiation treatment.}, } @article {pmid27197218, year = {2016}, author = {Basler, G and Nikoloski, Z and Larhlimi, A and Barabási, AL and Liu, YY}, title = {Control of fluxes in metabolic networks.}, journal = {Genome research}, volume = {26}, number = {7}, pages = {956-968}, pmid = {27197218}, issn = {1549-5469}, support = {P50 HG004233/HG/NHGRI NIH HHS/United States ; R01 HL118455/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/genetics/metabolism ; Computational Biology ; Evolution, Molecular ; Fungi/genetics/metabolism ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; *Metabolic Networks and Pathways ; Models, Biological ; Signal Transduction ; }, abstract = {Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism.}, } @article {pmid27196967, year = {2016}, author = {Lou, Y and Chen, Y}, title = {Simulating the multicellular homeostasis with a cell-based discrete receptor dynamics model: The non-mutational origin of cancer and aging.}, journal = {Journal of theoretical biology}, volume = {404}, number = {}, pages = {15-29}, doi = {10.1016/j.jtbi.2016.04.035}, pmid = {27196967}, issn = {1095-8541}, mesh = {Aging/*genetics ; Animals ; Cell Proliferation ; *Computer Simulation ; *Homeostasis ; Humans ; *Models, Biological ; Mutation/*genetics ; Neoplasms/*genetics ; Phenotype ; Receptors, Cell Surface/*metabolism ; Reproducibility of Results ; Time Factors ; }, abstract = {The purpose of the study is to investigate the multicellular homeostasis in epithelial tissues over very large timescales. Inspired by the receptor dynamics of IBCell model proposed by Rejniak et al. an on-grid agent-based model for multicellular system is constructed. Instead of observing the multicellular architectural morphologies, the diversity of homeostatic states is quantitatively analyzed through a substantial number of simulations by measuring three new order parameters, the phenotypic population structure, the average proliferation age and the relaxation time to stable homeostasis. Nearby the interfaces of distinct homeostatic phases in 3D phase diagrams of the three order parameters, intermediate quasi-stable phases of slow dynamics that features quasi-stability with a large spectrum of relaxation timescales are found. A further exploration on the static and dynamic correlations among the three order parameters reveals that the quasi-stable phases evolve towards two terminations, tumorigenesis and degeneration, which are respectively accompanied by rejuvenation and aging. With the exclusion of the environmental impact and the mutational strategies, the results imply that cancer and aging may share the non-mutational origin in the intrinsic slow dynamics of the multicellular systems.}, } @article {pmid27194700, year = {2016}, author = {Okie, JG and Smith, VH and Martin-Cereceda, M}, title = {Major evolutionary transitions of life, metabolic scaling and the number and size of mitochondria and chloroplasts.}, journal = {Proceedings. Biological sciences}, volume = {283}, number = {1831}, pages = {}, pmid = {27194700}, issn = {1471-2954}, mesh = {*Biological Evolution ; Chloroplasts/*metabolism ; Eukaryota/*physiology ; Mitochondria/*metabolism ; Models, Biological ; *Symbiosis ; }, abstract = {We investigate the effects of trophic lifestyle and two types of major evolutionary transitions in individuality-the endosymbiotic acquisition of organelles and development of multicellularity-on organellar and cellular metabolism and allometry. We develop a quantitative framework linking the size and metabolic scaling of eukaryotic cells to the abundance, size and metabolic scaling of mitochondria and chloroplasts and analyse a newly compiled, unprecedented database representing unicellular and multicellular cells covering diverse phyla and tissues. Irrespective of cellularity, numbers and total volumes of mitochondria scale linearly with cell volume, whereas chloroplasts scale sublinearly and sizes of both organelles remain largely invariant with cell size. Our framework allows us to estimate the metabolic scaling exponents of organelles and cells. Photoautotrophic cells and organelles exhibit photosynthetic scaling exponents always less than one, whereas chemoheterotrophic cells and organelles have steeper respiratory scaling exponents close to one. Multicellularity has no discernible effect on the metabolic scaling of organelles and cells. In contrast, trophic lifestyle has a profound and uniform effect, and our results suggest that endosymbiosis fundamentally altered the metabolic scaling of free-living bacterial ancestors of mitochondria and chloroplasts, from steep ancestral scaling to a shallower scaling in their endosymbiotic descendants.}, } @article {pmid27187178, year = {2016}, author = {Pârvu, O and Gilbert, D}, title = {A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking.}, journal = {PloS one}, volume = {11}, number = {5}, pages = {e0154847}, pmid = {27187178}, issn = {1932-6203}, mesh = {Algorithms ; Animals ; Cell Cycle/physiology ; *Computer Simulation ; Hemodynamics ; Inflammation ; *Models, Biological ; Models, Cardiovascular ; Rats ; *Spatio-Temporal Analysis ; Workflow ; }, abstract = {Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems.}, } @article {pmid27179461, year = {2016}, author = {Kaveh, K and Veller, C and Nowak, MA}, title = {Games of multicellularity.}, journal = {Journal of theoretical biology}, volume = {403}, number = {}, pages = {143-158}, doi = {10.1016/j.jtbi.2016.04.037}, pmid = {27179461}, issn = {1095-8541}, mesh = {Cell Proliferation ; Cells/*metabolism ; Cooperative Behavior ; *Game Theory ; Models, Biological ; Mutation Rate ; Numerical Analysis, Computer-Assisted ; Phenotype ; }, abstract = {Evolutionary game dynamics are often studied in the context of different population structures. Here we propose a new population structure that is inspired by simple multicellular life forms. In our model, cells reproduce but can stay together after reproduction. They reach complexes of a certain size, n, before producing single cells again. The cells within a complex derive payoff from an evolutionary game by interacting with each other. The reproductive rate of cells is proportional to their payoff. We consider all two-strategy games. We study deterministic evolutionary dynamics with mutations, and derive exact conditions for selection to favor one strategy over another. Our main result has the same symmetry as the well-known sigma condition, which has been proven for stochastic game dynamics and weak selection. For a maximum complex size of n=2 our result holds for any intensity of selection. For n≥3 it holds for weak selection. As specific examples we study the prisoner's dilemma and hawk-dove games. Our model advances theoretical work on multicellularity by allowing for frequency-dependent interactions within groups.}, } @article {pmid27172191, year = {2016}, author = {Paranjape, NP and Calvi, BR}, title = {The Histone Variant H3.3 Is Enriched at Drosophila Amplicon Origins but Does Not Mark Them for Activation.}, journal = {G3 (Bethesda, Md.)}, volume = {6}, number = {6}, pages = {1661-1671}, pmid = {27172191}, issn = {2160-1836}, support = {R01 GM061290/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *DNA Replication ; Drosophila/*genetics/*metabolism ; Drosophila Proteins/genetics/metabolism ; Gene Amplification ; Histones/genetics/*metabolism ; Mitosis/genetics ; Mutation ; Oogenesis/genetics ; *Replication Origin ; Transcription, Genetic ; }, abstract = {Eukaryotic DNA replication begins from multiple origins. The origin recognition complex (ORC) binds origin DNA and scaffolds assembly of a prereplicative complex (pre-RC), which is subsequently activated to initiate DNA replication. In multicellular eukaryotes, origins do not share a strict DNA consensus sequence, and their activity changes in concert with chromatin status during development, but mechanisms are ill-defined. Previous genome-wide analyses in Drosophila and other organisms have revealed a correlation between ORC binding sites and the histone variant H3.3. This correlation suggests that H3.3 may designate origin sites, but this idea has remained untested. To address this question, we examined the enrichment and function of H3.3 at the origins responsible for developmental gene amplification in the somatic follicle cells of the Drosophila ovary. We found that H3.3 is abundant at these amplicon origins. H3.3 levels remained high when replication initiation was blocked, indicating that H3.3 is abundant at the origins before activation of the pre-RC. H3.3 was also enriched at the origins during early oogenesis, raising the possibility that H3.3 bookmarks sites for later amplification. However, flies null mutant for both of the H3.3 genes in Drosophila did not have overt defects in developmental gene amplification or genomic replication, suggesting that H3.3 is not essential for the assembly or activation of the pre-RC at origins. Instead, our results imply that the correlation between H3.3 and ORC sites reflects other chromatin attributes that are important for origin function.}, } @article {pmid27172135, year = {2016}, author = {Kaczanowski, S}, title = {Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging.}, journal = {Physical biology}, volume = {13}, number = {3}, pages = {031001}, doi = {10.1088/1478-3975/13/3/031001}, pmid = {27172135}, issn = {1478-3975}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects/*physiology ; Biological Evolution ; Cell Respiration ; Cellular Senescence/*physiology ; Humans ; Mitochondria/*metabolism/pathology ; Neoplasms/drug therapy/*pathology ; Neurodegenerative Diseases/pathology ; Phylogeny ; }, abstract = {Programmed cell death is a basic cellular mechanism. Apoptotic-like programmed cell death (called apoptosis in animals) occurs in both unicellular and multicellular eukaryotes, and some apoptotic mechanisms are observed in bacteria. Endosymbiosis between mitochondria and eukaryotic cells took place early in the eukaryotic evolution, and some of the apoptotic-like mechanisms of mitochondria that were retained after this event now serve as parts of the eukaryotic apoptotic machinery. Apoptotic mechanisms have several functions in unicellular organisms: they include kin-selected altruistic suicide that controls population size, sharing common goods, and responding to viral infection. Apoptotic factors also have non-apoptotic functions. Apoptosis is involved in the cellular aging of eukaryotes, including humans. In addition, apoptosis is a key part of the innate tumor-suppression mechanism. Several anticancer drugs induce apoptosis, because apoptotic mechanisms are inactivated during oncogenesis. Because of the ancient history of apoptosis, I hypothesize that there is a deep relationship between mitochondrial metabolism, its role in aerobic versus anaerobic respiration, and the connection between apoptosis and cancer. Whereas normal cells rely primarily on oxidative mitochondrial respiration, most cancer cells use anaerobic metabolism. According to the Warburg hypothesis, the remodeling of the metabolism is one of the processes that leads to cancer. Recent studies indicate that anaerobic, non-mitochondrial respiration is particularly active in embryonic cells, stem cells, and aggressive stem-like cancer cells. Mitochondrial respiration is particularly active during the pathological aging of human cells in neurodegenerative diseases. According to the reversed Warburg hypothesis formulated by Demetrius, pathological aging is induced by mitochondrial respiration. Here, I advance the hypothesis that the stimulation of mitochondrial metabolism leads to pathological aging.}, } @article {pmid27160599, year = {2016}, author = {Rolff, J and Schmid-Hempel, P}, title = {Perspectives on the evolutionary ecology of arthropod antimicrobial peptides.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1695}, pages = {}, pmid = {27160599}, issn = {1471-2970}, support = {260986/ERC_/European Research Council/International ; 268853/ERC_/European Research Council/International ; }, mesh = {Animals ; Anti-Infective Agents/metabolism ; Antimicrobial Cationic Peptides/*genetics ; Arthropods/*genetics/immunology/microbiology ; *Evolution, Molecular ; *Gene Expression ; Host-Pathogen Interactions ; Immunity, Innate ; Insect Proteins/*genetics ; Insecta/genetics/immunology/microbiology ; Selection, Genetic ; }, abstract = {Antimicrobial peptides (AMPs) are important elements of the innate immune defence in multicellular organisms that target and kill microbes. Here, we reflect on the various points that are raised by the authors of the 11 contributions to a special issue of Philosophical Transactions on the 'evolutionary ecology of arthropod antimicrobial peptides'. We see five interesting topics emerging. (i) AMP genes in insects, and perhaps in arthropods more generally, evolve much slower than most other immune genes. One explanation refers to the constraints set by AMPs being part of a finely tuned defence system. A new view argues that AMPs are under strong stabilizing selection. Regardless, this striking observation still invites many more questions than have been answered so far. (ii) AMPs almost always are expressed in combinations and sometimes show expression patterns that are dependent on the infectious agent. While it is often assumed that this can be explained by synergistic interactions, such interactions have rarely been demonstrated and need to be studied further. Moreover, how to define synergy in the first place remains difficult and needs to be addressed. (iii) AMPs play a very important role in mediating the interaction between a host and its mutualistic or commensal microbes. This has only been studied in a very small number of (insect) species. It has become clear that the very same AMPs play different roles in different situations and hence are under concurrent selection. (iv) Different environments shape the physiology of organisms; especially the host-associated microbial communities should impact on the evolution host AMPs. Studies in social insects and some organisms from extreme environments seem to support this notion, but, overall, the evidence for adaptation of AMPs to a given environment is scant. (v) AMPs are considered or already developed as new drugs in medicine. However, bacteria can evolve resistance to AMPs. Therefore, in the light of our limited understanding of AMP evolution in the natural context, and also the very limited understanding of the evolution of resistance against AMPs in bacteria in particular, caution is recommended. What is clear though is that study of the ecology and evolution of AMPs in natural systems could inform many of these outstanding questions, including those related to medical applications and pathogen control.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.}, } @article {pmid27160500, year = {2016}, author = {Xue, W and Wang, H and Liu, G and Meng, L and Xiang, S and Ma, G and Li, W}, title = {Matrix description of the complete topology of three-dimensional cells.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {25877}, pmid = {27160500}, issn = {2045-2322}, mesh = {Algorithms ; Imaging, Three-Dimensional/*methods ; Matrix Bands ; }, abstract = {A new, efficient method based on a series of matrices is introduced to completely describe the detailed topology of individual domains and their topology evolution in three-dimensional cellular structures. With this approach, we found a lot of new topological grain forms which are never reported before, i.e., there are total 8 and 32 topological forms for 7- and 8-faced grains respectively, other than the reported 7 and 27. This method is proved to be a practical tool to predict all possible grain forms efficiently. Moreover, a connectivity index of grain forms serves as a new convenient differentiator of different multicellular structures.}, } @article {pmid27157793, year = {2016}, author = {Leliaert, F and Tronholm, A and Lemieux, C and Turmel, M and DePriest, MS and Bhattacharya, D and Karol, KG and Fredericq, S and Zechman, FW and Lopez-Bautista, JM}, title = {Chloroplast phylogenomic analyses reveal the deepest-branching lineage of the Chlorophyta, Palmophyllophyceae class. nov.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {25367}, pmid = {27157793}, issn = {2045-2322}, mesh = {Base Sequence ; Cell Nucleus/genetics ; Chlorophyta/classification/*genetics ; Chromosome Mapping ; DNA, Chloroplast/genetics ; DNA, Ribosomal/genetics ; Evolution, Molecular ; Genes, Plant ; *Genome, Chloroplast ; *Phylogeny ; }, abstract = {The green plants (Viridiplantae) are an ancient group of eukaryotes comprising two main clades: the Chlorophyta, which includes a wide diversity of green algae, and the Streptophyta, which consists of freshwater green algae and the land plants. The early-diverging lineages of the Viridiplantae comprise unicellular algae, and multicellularity has evolved independently in the two clades. Recent molecular data have revealed an unrecognized early-diverging lineage of green plants, the Palmophyllales, with a unique form of multicellularity, and typically found in deep water. The phylogenetic position of this enigmatic group, however, remained uncertain. Here we elucidate the evolutionary affinity of the Palmophyllales using chloroplast genomic, and nuclear rDNA data. Phylogenetic analyses firmly place the palmophyllalean Verdigellas peltata along with species of Prasinococcales (prasinophyte clade VI) in the deepest-branching clade of the Chlorophyta. The small, compact and intronless chloroplast genome (cpDNA) of V. peltata shows striking similarities in gene content and organization with the cpDNAs of Prasinococcales and the streptophyte Mesostigma viride, indicating that cpDNA architecture has been extremely well conserved in these deep-branching lineages of green plants. The phylogenetic distinctness of the Palmophyllales-Prasinococcales clade, characterized by unique ultrastructural features, warrants recognition of a new class of green plants, Palmophyllophyceae class. nov.}, } @article {pmid27148352, year = {2016}, author = {Wernick, RI and Estes, S and Howe, DK and Denver, DR}, title = {Paths of Heritable Mitochondrial DNA Mutation and Heteroplasmy in Reference and gas-1 Strains of Caenorhabditis elegans.}, journal = {Frontiers in genetics}, volume = {7}, number = {}, pages = {51}, pmid = {27148352}, issn = {1664-8021}, abstract = {Heteroplasmy-the presence of more than one mitochondrial DNA (mtDNA) sequence type in a cell, tissue, or individual-impacts human mitochondrial disease and numerous aging-related syndromes. Understanding the trans-generational dynamics of mtDNA is critical to understanding the underlying mechanisms of mitochondrial disease and evolution. We investigated mtDNA mutation and heteroplasmy using a set of wild-type (N2 strain) and mitochondrial electron transport chain (ETC) mutant (gas-1) mutant Caenorhabditis elegans mutation-accumulation (MA) lines. The N2 MA lines, derived from a previous experiment, were bottlenecked for 250 generations. The gas-1 MA lines were created for this study, and bottlenecked in the laboratory for up to 50 generations. We applied Illumina-MiSeq DNA sequencing to L1 larvae from five gas-1 MA lines and five N2 MA lines to detect and characterize mtDNA mutation and heteroplasmic inheritance patterns evolving under extreme drift. mtDNA copy number increased in both sets of MA lines: three-fold on average among the gas-1 MA lines and five-fold on average among N2 MA lines. Eight heteroplasmic single base substitution polymorphisms were detected in the gas-1 MA lines; only one was observed in the N2 MA lines. Heteroplasmy frequencies ranged broadly in the gas-1 MA lines, from as low as 2.3% to complete fixation (homoplasmy). An initially low-frequency (<5%) heteroplasmy discovered in the gas-1 progenitor was observed to fix in one gas-1 MA line, achieve higher frequency (37.4%) in another, and be lost in the other three lines. A similar low-frequency heteroplasmy was detected in the N2 progenitor, but was lost in all five N2 MA lines. We identified three insertion-deletion (indel) heteroplasmies in gas-1 MA lines and six indel variants in the N2 MA lines, most occurring at homopolymeric nucleotide runs. The observed bias toward accumulation of single nucleotide polymorphisms in gas-1 MA lines is consistent with the idea that impaired mitochondrial activity renders mtDNA more vulnerable to this type of mutation. The consistent increases in mtDNA copy number implies that extreme genetic drift provides a permissive environment for elevated organelle genome copy number in C. elegans reference and gas-1 strains. This study broadens our understanding of the heteroplasmic mitochondrial mutation process in a multicellular model organism.}, } @article {pmid27146690, year = {2016}, author = {Pentz, JT and Taylor, BP and Ratcliff, WC}, title = {Apoptosis in snowflake yeast: novel trait, or side effect of toxic waste?.}, journal = {Journal of the Royal Society, Interface}, volume = {13}, number = {118}, pages = {}, pmid = {27146690}, issn = {1742-5662}, mesh = {Apoptosis/*genetics ; *Fungal Proteins/genetics/metabolism ; *Quantitative Trait Loci ; *Transcription Factors/genetics/metabolism ; *Yeasts/genetics/metabolism ; }, abstract = {Recent experiments evolving de novo multicellularity in yeast have found that large cluster-forming genotypes also exhibit higher rates of programmed cell death (apoptosis). This was previously interpreted as the evolution of a simple form of cellular division of labour: apoptosis results in the scission of cell-cell connections, allowing snowflake yeast to produce proportionally smaller, faster-growing propagules. Through spatial simulations, Duran-Nebreda and Solé (J. R. Soc. Interface 12, 20140982 (doi:10.1073/pnas.1115323109)) develop the novel null hypothesis that apoptosis is not an adaptation, per se, but is instead caused by the accumulation of toxic metabolites in large clusters. Here we test this hypothesis by synthetically creating unicellular derivatives of snowflake yeast through functional complementation with the ancestral ACE2 allele. We find that multicellular snowflake yeast with elevated apoptosis exhibit a similar rate of apoptosis when cultured as single cells. We also show that larger snowflake yeast clusters tend to contain a greater fraction of older, senescent cells, which may explain why larger clusters of a given genotype are more apoptotic. Our results show that apoptosis is not caused by side effects of spatial structure, such as starvation or waste product accumulation, and are consistent with the hypothesis that elevated apoptosis is a trait that co-evolves with large cluster size.}, } @article {pmid27145840, year = {2016}, author = {Joerger, AC and Fersht, AR}, title = {The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches.}, journal = {Annual review of biochemistry}, volume = {85}, number = {}, pages = {375-404}, doi = {10.1146/annurev-biochem-060815-014710}, pmid = {27145840}, issn = {1545-4509}, support = {MC_EX_G0901534/MRC_/Medical Research Council/United Kingdom ; MC_UP_A024_1010/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Antineoplastic Agents, Alkylating/chemical synthesis/*therapeutic use ; Cell Cycle Proteins ; Clinical Trials as Topic ; Drug Design ; *Gene Expression Regulation, Neoplastic ; Humans ; Molecular Docking Simulation ; *Molecular Targeted Therapy ; Mutation ; Neoplasms/*drug therapy/genetics/metabolism/pathology ; Nuclear Proteins/antagonists & inhibitors/chemistry/genetics/metabolism ; Protein Multimerization ; Protein Structure, Secondary ; Proto-Oncogene Proteins/antagonists & inhibitors/chemistry/genetics/metabolism ; Proto-Oncogene Proteins c-mdm2/antagonists & inhibitors/chemistry/genetics/metabolism ; Signal Transduction ; Tumor Suppressor Protein p53/*agonists/chemistry/genetics/metabolism ; }, abstract = {Inactivation of the transcription factor p53, through either direct mutation or aberrations in one of its many regulatory pathways, is a hallmark of virtually every tumor. In recent years, screening for p53 activators and a better understanding of the molecular mechanisms of oncogenic perturbations of p53 function have opened up a host of novel avenues for therapeutic intervention in cancer: from the structure-guided design of chemical chaperones to restore the function of conformationally unstable p53 cancer mutants, to the development of potent antagonists of the negative regulators MDM2 and MDMX and other modulators of the p53 pathway for the treatment of cancers with wild-type p53. Some of these compounds have now moved from proof-of-concept studies into clinical trials, with prospects for further, personalized anticancer medicines. We trace the structural evolution of the p53 pathway, from germ-line surveillance in simple multicellular organisms to its pluripotential role in humans.}, } @article {pmid27139940, year = {2016}, author = {Joachimczak, M and Suzuki, R and Arita, T}, title = {Artificial Metamorphosis: Evolutionary Design of Transforming, Soft-Bodied Robots.}, journal = {Artificial life}, volume = {22}, number = {3}, pages = {271-298}, doi = {10.1162/ARTL_a_00207}, pmid = {27139940}, issn = {1064-5462}, mesh = {Animals ; Biological Evolution ; Larva ; Locomotion ; *Metamorphosis, Biological ; *Models, Biological ; *Robotics ; }, abstract = {We show how the concept of metamorphosis, together with a biologically inspired model of multicellular development, can be used to evolve soft-bodied robots that are adapted to two very different tasks, such as being able to move in an aquatic and in a terrestrial environment. Each evolved solution defines two pairs of morphologies and controllers, together with a process of transforming one pair into the other. Animats develop from a single cell and grow through cellular divisions and deaths until they reach an initial larval form adapted to a first environment. To obtain the adult form adapted to a second environment, the larva undergoes metamorphosis, during which new cells are added or removed and its controller is modified. Importantly, our approach assumes nothing about what morphologies or methods of locomotion are preferred. Instead, it successfully searches the vast space of possible designs and comes up with complex, surprising, lifelike solutions that are reminiscent of amphibian metamorphosis. We analyze obtained solutions and investigate whether the morphological changes during metamorphosis are indeed adaptive. We then compare the effectiveness of three different types of selective pressures used to evolve metamorphic individuals. Finally, we investigate potential advantages of using metamorphosis to automatically produce soft-bodied designs by comparing the performance of metamorphic individuals with their specialized counterparts and designs that are robust to both environments.}, } @article {pmid27139112, year = {2016}, author = {Bastiaans, E and Debets, AJ and Aanen, DK}, title = {Experimental evolution reveals that high relatedness protects multicellular cooperation from cheaters.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {11435}, pmid = {27139112}, issn = {2041-1723}, mesh = {Cell Proliferation ; *Clonal Evolution ; *Microbial Interactions ; Mutation ; Neurospora crassa/*genetics/growth & development ; Spores, Fungal/genetics/growth & development ; }, abstract = {In multicellular organisms, there is a potential risk that cheating mutants gain access to the germline. Development from a single-celled zygote resets relatedness among cells to its maximum value each generation, which should accomplish segregation of cheating mutants from non-cheaters and thereby protect multicellular cooperation. Here we provide the crucial direct comparison between high- and low-relatedness conditions to test this hypothesis. We allow two variants of the fungus Neurospora crassa to evolve, one with and one without the ability to form chimeras with other individuals, thus generating two relatedness levels. While multicellular cooperation remains high in the high-relatedness lines, it significantly decreases in all replicate low-relatedness lines, resulting in an average threefold decrease in spore yield. This reduction is caused by cheating mutants with reduced investment in somatic functions, but increased competitive success when fusing with non-cheaters. Our experiments demonstrate that high genetic relatedness is crucial to sustain multicellular cooperation.}, } @article {pmid27137289, year = {2016}, author = {Jung, SY and Kwon, DH and Yang, SH and Han, SK}, title = {Inter-cell interference mitigation in multi-cellular visible light communications.}, journal = {Optics express}, volume = {24}, number = {8}, pages = {8512-8526}, doi = {10.1364/OE.24.008512}, pmid = {27137289}, issn = {1094-4087}, abstract = {Inter-cell interference hinders multi-cellular optical wireless communication to support various applications. We proposed and experimentally demonstrated a multicarrier-based cell partitioning scheme, combined with frequency reuse, which could be effective in optical communications although it is inefficient in RF wireless communications. For multicarrier-based cell partitioning, Orthogonal frequency division multiplexing-based multiple access (OFDMA) was employed to accommodate multi-cellular optical wireless communications without a large guard band between adjacent cells and without additional RF components. Moreover, we employed filter bank-based multicarrier (FBMC) to mitigate inter-cell interference generated in OFDMA-based cell partitioning due to asynchronous signals originated from RF path difference. By using FBMC-based cell partitioning, inter-cell interference could be effectively mitigated as well as capacity and spectral efficiency were improved about 1.5 times compared to those of OFDMA. Because no cyclic prefix (CP) is required in FBMC, the improvement factor could be increased if there is a large RF path difference between lighting cells. Moreover, it could be a stronger solution when many neighboring cells exist causing large interference. The proposed multicarrier-based cell partitioning combined with FBMC will effectively support visible light communication (VLC)-based localization-based services (LBS) and indoor positioning system by transparently providing trilateration-based positioning method.}, } @article {pmid27128951, year = {2016}, author = {Torday, JS}, title = {Life Is Simple-Biologic Complexity Is an Epiphenomenon.}, journal = {Biology}, volume = {5}, number = {2}, pages = {}, pmid = {27128951}, issn = {2079-7737}, support = {R01 HL055268/HL/NHLBI NIH HHS/United States ; }, abstract = {Life originated from unicellular organisms by circumventing the Second Law of Thermodynamics using the First Principles of Physiology, namely negentropy, chemiosmosis and homeostatic regulation of calcium and lipids. It is hypothesized that multicellular organisms are merely contrivances or tools, used by unicellular organisms as agents for the acquisition of epigenetic inheritance. The First Principles of Physiology, which initially evolved in unicellular organisms are the exapted constraints that maintain, sustain and perpetuate that process. To ensure fidelity to this mechanism, we must return to the first principles of the unicellular state as the determinants of the primary level of selection pressure during the life cycle. The power of this approach is reflected by examples of its predictive value. This perspective on life is a "game changer", mechanistically rendering transparent many dogmas, teleologies and tautologies that constrain the current descriptive view of Biology.}, } @article {pmid27122563, year = {2016}, author = {Boisseau, RP and Vogel, D and Dussutour, A}, title = {Habituation in non-neural organisms: evidence from slime moulds.}, journal = {Proceedings. Biological sciences}, volume = {283}, number = {1829}, pages = {}, pmid = {27122563}, issn = {1471-2954}, mesh = {Animals ; Biological Evolution ; Caffeine ; Chemotaxis/physiology ; Habituation, Psychophysiologic/*physiology ; Learning/physiology ; Models, Biological ; Phylogeny ; Physarum polycephalum/*physiology ; Quinine ; }, abstract = {Learning, defined as a change in behaviour evoked by experience, has hitherto been investigated almost exclusively in multicellular neural organisms. Evidence for learning in non-neural multicellular organisms is scant, and only a few unequivocal reports of learning have been described in single-celled organisms. Here we demonstrate habituation, an unmistakable form of learning, in the non-neural organism Physarum polycephalum In our experiment, using chemotaxis as the behavioural output and quinine or caffeine as the stimulus, we showed that P. polycephalum learnt to ignore quinine or caffeine when the stimuli were repeated, but responded again when the stimulus was withheld for a certain time. Our results meet the principle criteria that have been used to demonstrate habituation: responsiveness decline and spontaneous recovery. To distinguish habituation from sensory adaptation or motor fatigue, we also show stimulus specificity. Our results point to the diversity of organisms lacking neurons, which likely display a hitherto unrecognized capacity for learning, and suggest that slime moulds may be an ideal model system in which to investigate fundamental mechanisms underlying learning processes. Besides, documenting learning in non-neural organisms such as slime moulds is centrally important to a comprehensive, phylogenetic understanding of when and where in the tree of life the earliest manifestations of learning evolved.}, } @article {pmid27114036, year = {2016}, author = {Sebé-Pedrós, A and Ballaré, C and Parra-Acero, H and Chiva, C and Tena, JJ and Sabidó, E and Gómez-Skarmeta, JL and Di Croce, L and Ruiz-Trillo, I}, title = {The Dynamic Regulatory Genome of Capsaspora and the Origin of Animal Multicellularity.}, journal = {Cell}, volume = {165}, number = {5}, pages = {1224-1237}, pmid = {27114036}, issn = {1097-4172}, support = {616960/ERC_/European Research Council/International ; }, mesh = {Animals ; *Biological Evolution ; Eukaryota/classification/cytology/*genetics ; Gene Regulatory Networks ; Genome ; Histones/metabolism ; Humans ; Protein Processing, Post-Translational ; RNA, Untranslated ; *Regulatory Elements, Transcriptional ; }, abstract = {The unicellular ancestor of animals had a complex repertoire of genes linked to multicellular processes. This suggests that changes in the regulatory genome, rather than in gene innovation, were key to the origin of animals. Here, we carry out multiple functional genomic assays in Capsaspora owczarzaki, the unicellular relative of animals with the largest known gene repertoire for transcriptional regulation. We show that changing chromatin states, differential lincRNA expression, and dynamic cis-regulatory sites are associated with life cycle transitions in Capsaspora. Moreover, we demonstrate conservation of animal developmental transcription-factor networks and extensive network interconnection in this premetazoan organism. In contrast, however, Capsaspora lacks animal promoter types, and its regulatory sites are small, proximal, and lack signatures of animal enhancers. Overall, our results indicate that the emergence of animal multicellularity was linked to a major shift in genome cis-regulatory complexity, most notably the appearance of distal enhancer regulation.}, } @article {pmid27112670, year = {2016}, author = {Obermeier, B and Verma, A and Ransohoff, RM}, title = {The blood-brain barrier.}, journal = {Handbook of clinical neurology}, volume = {133}, number = {}, pages = {39-59}, doi = {10.1016/B978-0-444-63432-0.00003-7}, pmid = {27112670}, issn = {0072-9752}, mesh = {Animals ; Biological Transport/physiology ; Blood-Brain Barrier/anatomy & histology/*physiology ; Cerebrospinal Fluid/physiology ; Endothelial Cells/physiology ; Humans ; Neovascularization, Physiologic/*physiology ; Neuroglia/physiology ; Neurons/physiology ; }, abstract = {In autoimmune neurologic disorders, the blood-brain barrier (BBB) plays a central role in immunopathogenesis, since this vascular interface is an entry path for cells and effector molecules of the peripheral immune system to reach the target organ, the central nervous system (CNS). The BBB's unique anatomic structure and the tightly regulated interplay of its cellular and acellular components allow for maintenance of brain homeostasis, regulation of influx and efflux, and protection from harm; these ensure an optimal environment for the neuronal network to function properly. In both health and disease, the BBB acts as mediator between the periphery and the CNS. For example, immune cell trafficking through the cerebral vasculature is essential to clear microbes or cell debris from neural tissues, while poorly regulated cellular transmigration can underlie or worsen CNS pathology. In this chapter, we focus on the specialized multicellular structure and function of the BBB/neurovascular unit and discuss how BBB breakdown can precede or be a consequence of neuroinflammation. We introduce the blood-cerebrospinal fluid barrier and include a brief aside about evolutionary aspects of barrier formation and refinements. Lastly, since restoration of barrier function is considered key to ameliorate neurologic disease, we speculate about new therapeutic avenues to repair a damaged BBB.}, } @article {pmid27107900, year = {2016}, author = {Akasov, R and Zaytseva-Zotova, D and Burov, S and Leko, M and Dontenwill, M and Chiper, M and Vandamme, T and Markvicheva, E}, title = {Formation of multicellular tumor spheroids induced by cyclic RGD-peptides and use for anticancer drug testing in vitro.}, journal = {International journal of pharmaceutics}, volume = {506}, number = {1-2}, pages = {148-157}, doi = {10.1016/j.ijpharm.2016.04.005}, pmid = {27107900}, issn = {1873-3476}, mesh = {Antineoplastic Agents/*pharmacology ; Cell Culture Techniques/methods ; Cell Line, Tumor ; Chemistry, Pharmaceutical/methods ; Curcumin/pharmacology ; Dacarbazine/analogs & derivatives/pharmacology ; Doxorubicin/pharmacology ; Drug Screening Assays, Antitumor/*methods ; HCT116 Cells ; Hep G2 Cells ; Humans ; MCF-7 Cells ; Oligopeptides/*pharmacology ; Peptides, Cyclic/*pharmacology ; Spheroids, Cellular/*drug effects ; Temozolomide ; }, abstract = {Development of novel anticancer formulations is a priority challenge in biomedicine. However, in vitro models based on monolayer cultures (2D) which are currently used for cytotoxicity tests leave much to be desired. More and more attention is focusing on 3D in vitro systems which can better mimic solid tumors. The aim of the study was to develop a novel one-step highly reproducible technique for multicellular tumor spheroid (MTS) formation using synthetic cyclic RGD-peptides, and to demonstrate availability of the spheroids as 3D in vitro model for antitumor drug testing. Cell self-assembly effect induced by addition of both linear and cyclic RGD-peptides directly to monolayer cultures was studied for 12 cell lines of various origins, including tumor cells (e.i. U-87 MG, MCF-7, M-3, HCT-116) and normal cells, in particular L-929, BNL.CL2, HepG2. Cyclo-RGDfK and its modification with triphenylphosphonium cation (TPP), namely cyclo-RGDfK(TPP) in a range of 10-100μM were found to induce spheroid formation. The obtained spheroids were unimodal with mean sizes in a range of 60-120μm depending on cell line and serum content in culture medium. The spheroids were used as 3D in vitro model, in order to evaluate cytotoxicity effects of antitumor drugs (doxorubicin, curcumin, temozolomide). The developed technique could be proposed as a promising tool for in vitro test of novel antitumor drugs.}, } @article {pmid27102219, year = {2016}, author = {Hanschen, ER and Marriage, TN and Ferris, PJ and Hamaji, T and Toyoda, A and Fujiyama, A and Neme, R and Noguchi, H and Minakuchi, Y and Suzuki, M and Kawai-Toyooka, H and Smith, DR and Sparks, H and Anderson, J and Bakarić, R and Luria, V and Karger, A and Kirschner, MW and Durand, PM and Michod, RE and Nozaki, H and Olson, BJ}, title = {The Gonium pectorale genome demonstrates co-option of cell cycle regulation during the evolution of multicellularity.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {11370}, pmid = {27102219}, issn = {2041-1723}, support = {R01 HD091846/HD/NICHD NIH HHS/United States ; P20 GM103418/GM/NIGMS NIH HHS/United States ; GM103785-02/GM/NIGMS NIH HHS/United States ; P20 GM103638/GM/NIGMS NIH HHS/United States ; R01 GM103785/GM/NIGMS NIH HHS/United States ; P20GM103418/GM/NIGMS NIH HHS/United States ; T32 GM084905/GM/NIGMS NIH HHS/United States ; GM084905/GM/NIGMS NIH HHS/United States ; P20GM103638/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Cell Cycle Checkpoints/*genetics ; Chlamydomonas/cytology/*genetics ; Chlorophyta/classification/cytology/*genetics ; *Gene Expression Regulation, Plant ; Genome Size ; *Genome, Plant ; Phylogeny ; Plant Cells/metabolism ; Plasmids/chemistry/metabolism ; Retinoblastoma Protein/genetics/metabolism ; Transformation, Genetic ; }, abstract = {The transition to multicellularity has occurred numerous times in all domains of life, yet its initial steps are poorly understood. The volvocine green algae are a tractable system for understanding the genetic basis of multicellularity including the initial formation of cooperative cell groups. Here we report the genome sequence of the undifferentiated colonial alga, Gonium pectorale, where group formation evolved by co-option of the retinoblastoma cell cycle regulatory pathway. Significantly, expression of the Gonium retinoblastoma cell cycle regulator in unicellular Chlamydomonas causes it to become colonial. The presence of these changes in undifferentiated Gonium indicates extensive group-level adaptation during the initial step in the evolution of multicellularity. These results emphasize an early and formative step in the evolution of multicellularity, the evolution of cell cycle regulation, one that may shed light on the evolutionary history of other multicellular innovations and evolutionary transitions.}, } @article {pmid27094475, year = {2016}, author = {Horst, NA and Reski, R}, title = {Alternation of generations - unravelling the underlying molecular mechanism of a 165-year-old botanical observation.}, journal = {Plant biology (Stuttgart, Germany)}, volume = {18}, number = {4}, pages = {549-551}, doi = {10.1111/plb.12468}, pmid = {27094475}, issn = {1438-8677}, mesh = {Animals ; Bryopsida/*genetics/growth & development/physiology ; Diploidy ; *Evolution, Molecular ; Germ Cells, Plant ; Haploidy ; *Life Cycle Stages ; Meiosis ; Models, Molecular ; Phylogeny ; Plant Proteins/*genetics ; Reproduction ; Reproduction, Asexual ; }, abstract = {Characteristically, land plants exhibit a life cycle with an 'alternation of generations' and thus alternate between a haploid gametophyte and a diploid sporophyte. At meiosis and fertilisation the transitions between these two ontogenies take place in distinct single stem cells. The evolutionary invention of an embryo, and thus an upright multicellular sporophyte, in the ancestor of land plants formed the basis for the evolution of increasingly complex plant morphologies shaping Earth's ecosystems. Recent research employing the moss Physcomitrella patens revealed the homeotic gene BELL1 as a master regulator of the gametophyte-to-sporophyte transition. Here, we discuss these findings in the context of classical botanical observations.}, } @article {pmid27091969, year = {2016}, author = {Au, SH and Storey, BD and Moore, JC and Tang, Q and Chen, YL and Javaid, S and Sarioglu, AF and Sullivan, R and Madden, MW and O'Keefe, R and Haber, DA and Maheswaran, S and Langenau, DM and Stott, SL and Toner, M}, title = {Clusters of circulating tumor cells traverse capillary-sized vessels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {113}, number = {18}, pages = {4947-4952}, pmid = {27091969}, issn = {1091-6490}, support = {F33 GM109574/GM/NIGMS NIH HHS/United States ; P41 EB002503/EB/NIBIB NIH HHS/United States ; R24 OD016761/OD/NIH HHS/United States ; U01 EB012493/EB/NIBIB NIH HHS/United States ; }, mesh = {Capillaries/*pathology ; *Cell Movement ; Humans ; *Neoplastic Cells, Circulating ; }, abstract = {Multicellular aggregates of circulating tumor cells (CTC clusters) are potent initiators of distant organ metastasis. However, it is currently assumed that CTC clusters are too large to pass through narrow vessels to reach these organs. Here, we present evidence that challenges this assumption through the use of microfluidic devices designed to mimic human capillary constrictions and CTC clusters obtained from patient and cancer cell origins. Over 90% of clusters containing up to 20 cells successfully traversed 5- to 10-μm constrictions even in whole blood. Clusters rapidly and reversibly reorganized into single-file chain-like geometries that substantially reduced their hydrodynamic resistances. Xenotransplantation of human CTC clusters into zebrafish showed similar reorganization and transit through capillary-sized vessels in vivo. Preliminary experiments demonstrated that clusters could be disrupted during transit using drugs that affected cellular interaction energies. These findings suggest that CTC clusters may contribute a greater role to tumor dissemination than previously believed and may point to strategies for combating CTC cluster-initiated metastasis.}, } @article {pmid27087837, year = {2016}, author = {Aktipis, A}, title = {Principles of cooperation across systems: from human sharing to multicellularity and cancer.}, journal = {Evolutionary applications}, volume = {9}, number = {1}, pages = {17-36}, pmid = {27087837}, issn = {1752-4571}, support = {R01 CA170595/CA/NCI NIH HHS/United States ; }, abstract = {From cells to societies, several general principles arise again and again that facilitate cooperation and suppress conflict. In this study, I describe three general principles of cooperation and how they operate across systems including human sharing, cooperation in animal and insect societies and the massively large-scale cooperation that occurs in our multicellular bodies. The first principle is that of Walk Away: that cooperation is enhanced when individuals can leave uncooperative partners. The second principle is that resource sharing is often based on the need of the recipient (i.e., need-based transfers) rather than on strict account-keeping. And the last principle is that effective scaling up of cooperation requires increasingly sophisticated and costly cheater suppression mechanisms. By comparing how these principles operate across systems, we can better understand the constraints on cooperation. This can facilitate the discovery of novel ways to enhance cooperation and suppress cheating in its many forms, from social exploitation to cancer.}, } @article {pmid27086973, year = {2016}, author = {Woolsey, TA}, title = {Re: Woolsey TA, van der Loos H. 1970. The structural organization of layer IV in the somatosensory region (S I) of mouse cerebral cortex. Brain Res. 17: 205-242.}, journal = {Brain research}, volume = {1645}, number = {}, pages = {22-24}, doi = {10.1016/j.brainres.2016.04.029}, pmid = {27086973}, issn = {1872-6240}, mesh = {Animals ; Autoradiography/history ; History, 20th Century ; Mice ; Neuroanatomical Tract-Tracing Techniques/history/methods ; Neuroanatomy/*history/methods ; Somatosensory Cortex/*anatomy & histology ; Vibrissae ; }, abstract = {UNLABELLED: Axoplasmically transported proteins synthesized in neuronal somata labeled by radioactively labeled amino acids (tritium), following local targeted injections for tracing of pathways in the central nervous system using autoradiography. Results from a number of neuronal systems, including: the rat olfactory bulb; cortico-thalamic projections in the mouse; commissural connections of the rat hippocampus; and retinal projections in the monkey and chick are documented. Pathway origins are clear, as the number and distribution of the labeled cells and the normal structure of the injection site is preserved. Light and electron microscopic autoradiography shows that proteins are transported, at two rates: rapid transport (>100mm/day) of fewer proteins accumulating in axon terminals; and, slow transport (1-5mm/day) of the bulk of labeled proteins distributed along the length of axons. Different survival times can be selected to evaluate terminal projection field(s) or pathways from origin to termination. The clarity of autoradiographic labeling of pathways and their terminations is comparable to other techniques (such as the Nauta-Gygax and the Fink-Heimer methods and the electron microscopy of terminal degeneration). Labeled amino acids do not label molecules in fibers of passage and there is no retrograde transport of labeled material from the axon terminals. The functional polarity of fiber pathways can be easily established. We summarize the merits of this technique is based upon an established physiological properties of neurons that are summarized in contrast to currently used techniques dependent upon pathological changes in neurons, axons, or axonal terminals.

ABSTRACT: The cytoarchitecture of layer IV in mouse SmI cerebral cortex was examined in.formalin-fixed, Nissl-stained and Cox-fixed, Golgi-Nissl-stained sections cut coronally and tangentially to the pia, A multicellular cytoarchitectonic unit is described in layer IV, roughly cylindrical, 100-400um in diameter, and perpendicular to the pia. Because of their characteristic shape we call these structures barrels. Each barrel is a ring of neurons, the side, which surrounds a less cellular hollow. The nearly acellular reigion surrounding each barrel and separating adjacent barrels is the septum. Barrels are discussed in relation to observations reported in several earlier papers on the mouse cortex. The barrel field (all barrels) has remarkable constancy by all measures: from one hemisphere to the next and from one specimen to the next. A consistent part of the barrel field is the postero-medial barrel subield (PMBSF). Barrels in the PMBSF are larger, elliptical in shape, organized into five distinct rows and their numbers are constant. It is postulated that each barrel in the PMBSF is the cortical correlate of a contralateral mystacial vibrissa (whisker). On the basis of counts of barrels and of all facial sinus hairs a 'one barrel-one vibrissa' hypothesis is proposed. The general hypothesis is that barrels are the morphological manifestation in layer IV of the functional cortical columns discovered by physiologists. The barrels offer excellent opportunities for integrated studies of sensory cerebral cortex at a degree of resolution previously not possible. This article is part of a Special Issue entitled SI:50th Anniversary Issue.}, } @article {pmid27077531, year = {2016}, author = {Møller, HD and Bojsen, RK and Tachibana, C and Parsons, L and Botstein, D and Regenberg, B}, title = {Genome-wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {110}, pages = {e54239 |}, pmid = {27077531}, issn = {1940-087X}, mesh = {DNA, Circular/genetics/*isolation & purification ; DNA, Fungal/genetics/*isolation & purification ; Eukaryotic Cells ; Extrachromosomal Inheritance/*genetics ; Genome ; Genome, Fungal ; Saccharomyces cerevisiae/*genetics ; }, abstract = {Extrachromosomal circular DNAs (eccDNAs) are common genetic elements in Saccharomyces cerevisiae and are reported in other eukaryotes as well. EccDNAs contribute to genetic variation among somatic cells in multicellular organisms and to evolution of unicellular eukaryotes. Sensitive methods for detecting eccDNA are needed to clarify how these elements affect genome stability and how environmental and biological factors induce their formation in eukaryotic cells. This video presents a sensitive eccDNA-purification method called Circle-Seq. The method encompasses column purification of circular DNA, removal of remaining linear chromosomal DNA, rolling-circle amplification of eccDNA, deep sequencing, and mapping. Extensive exonuclease treatment was required for sufficient linear chromosomal DNA degradation. The rolling-circle amplification step by φ29 polymerase enriched for circular DNA over linear DNA. Validation of the Circle-Seq method on three S. cerevisiae CEN.PK populations of 10(10) cells detected hundreds of eccDNA profiles in sizes larger than 1 kilobase. Repeated findings of ASP3-1, COS111, CUP1, RSC30, HXT6, HXT7 genes on circular DNA in both S288c and CEN.PK suggests that DNA circularization is conserved between strains at these loci. In sum, the Circle-Seq method has broad applicability for genome-scale screening for eccDNA in eukaryotes as well as for detecting specific eccDNA types.}, } @article {pmid27053655, year = {2016}, author = {Duran-Nebreda, S and Bonforti, A and Montañez, R and Valverde, S and Solé, R}, title = {Emergence of proto-organisms from bistable stochastic differentiation and adhesion.}, journal = {Journal of the Royal Society, Interface}, volume = {13}, number = {117}, pages = {}, pmid = {27053655}, issn = {1742-5662}, mesh = {*Biological Evolution ; *Models, Biological ; }, abstract = {The rise of multicellularity in the early evolution of life represents a major challenge for evolutionary biology. Guidance for finding answers has emerged from disparate fields, from phylogenetics to modelling and synthetic biology, but little is known about the potential origins of multicellular aggregates before genetic programmes took full control of developmental processes. Such aggregates should involve spatial organization of differentiated cells and the modification of flows and concentrations of metabolites within well-defined boundaries. Here, we show that, in an environment where limited nutrients and toxic metabolites are introduced, a population of cells capable of stochastic differentiation and differential adhesion can develop into multicellular aggregates with conflict mediation mechanisms and a complex internal structure. The morphospace of possible patterns is shown to be very rich, including proto-organisms that display a high degree of organizational complexity, far beyond simple heterogeneous populations of cells. Our findings reveal that there is a potentially enormous richness of organismal complexity between simple mixed cooperators and embodied living organisms.}, } @article {pmid27044515, year = {2016}, author = {Barth, E and Hübler, R and Baniahmad, A and Marz, M}, title = {The Evolution of COP9 Signalosome in Unicellular and Multicellular Organisms.}, journal = {Genome biology and evolution}, volume = {8}, number = {4}, pages = {1279-1289}, pmid = {27044515}, issn = {1759-6653}, mesh = {Alternative Splicing ; Animals ; COP9 Signalosome Complex ; *Evolution, Molecular ; Exons ; Humans ; Introns ; Multiprotein Complexes/*genetics ; Peptide Hydrolases/*genetics ; Phylogeny ; Protein Subunits/genetics ; }, abstract = {The COP9 signalosome (CSN) is a highly conserved protein complex, recently being crystallized for human. In mammals and plants the COP9 complex consists of nine subunits, CSN 1-8 and CSNAP. The CSN regulates the activity of culling ring E3 ubiquitin and plays central roles in pleiotropy, cell cycle, and defense of pathogens. Despite the interesting and essential functions, a thorough analysis of the CSN subunits in evolutionary comparative perspective is missing. Here we compared 61 eukaryotic genomes including plants, animals, and yeasts genomes and show that the most conserved subunits of eukaryotes among the nine subunits are CSN2 and CSN5. This may indicate a strong evolutionary selection for these two subunits. Despite the strong conservation of the protein sequence, the genomic structures of the intron/exon boundaries indicate no conservation at genomic level. This suggests that the gene structure is exposed to a much less selection compared with the protein sequence. We also show the conservation of important active domains, such as PCI (proteasome lid-CSN-initiation factor) and MPN (MPR1/PAD1 amino-terminal). We identified novel exons and alternative splicing variants for all CSN subunits. This indicates another level of complexity of the CSN. Notably, most COP9-subunits were identified in all multicellular and unicellular eukaryotic organisms analyzed, but not in prokaryotes or archaeas. Thus, genes encoding CSN subunits present in all analyzed eukaryotes indicate the invention of the signalosome at the root of eukaryotes. The identification of alternative splice variants indicates possible "mini-complexes" or COP9 complexes with independent subunits containing potentially novel and not yet identified functions.}, } @article {pmid27040616, year = {2016}, author = {Moody, LA and Saidi, Y and Gibbs, DJ and Choudhary, A and Holloway, D and Vesty, EF and Bansal, KK and Bradshaw, SJ and Coates, JC}, title = {An ancient and conserved function for Armadillo-related proteins in the control of spore and seed germination by abscisic acid.}, journal = {The New phytologist}, volume = {211}, number = {3}, pages = {940-951}, pmid = {27040616}, issn = {1469-8137}, support = {BB/D007550/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Abscisic Acid/*pharmacology ; Arabidopsis/drug effects/*metabolism ; Armadillo Domain Proteins/*metabolism ; Bryopsida/drug effects/*metabolism ; *Conserved Sequence ; *Germination/drug effects ; Mutation/genetics ; Plant Proteins/*metabolism ; Seeds/drug effects/*metabolism ; Selaginellaceae/drug effects/*metabolism ; Sequence Homology, Amino Acid ; Spores/metabolism ; }, abstract = {Armadillo-related proteins regulate development throughout eukaryotic kingdoms. In the flowering plant Arabidopsis thaliana, Armadillo-related ARABIDILLO proteins promote multicellular root branching. ARABIDILLO homologues exist throughout land plants, including early-diverging species lacking true roots, suggesting that early-evolving ARABIDILLOs had additional biological roles. Here we investigated, using molecular genetics, the conservation and diversification of ARABIDILLO protein function in plants separated by c. 450 million years of evolution. We demonstrate that ARABIDILLO homologues in the moss Physcomitrella patens regulate a previously undiscovered inhibitory effect of abscisic acid (ABA) on spore germination. Furthermore, we show that A. thaliana ARABIDILLOs function similarly during seed germination. Early-diverging ARABIDILLO homologues from both P. patens and the lycophyte Selaginella moellendorffii can substitute for ARABIDILLO function during A. thaliana root development and seed germination. We conclude that (1) ABA was co-opted early in plant evolution to regulate functionally analogous processes in spore- and seed-producing plants and (2) plant ARABIDILLO germination functions were co-opted early into both gametophyte and sporophyte, with a specific rooting function evolving later in the land plant lineage.}, } @article {pmid27034283, year = {2016}, author = {Rosenberg, E and Zilber-Rosenberg, I}, title = {Microbes Drive Evolution of Animals and Plants: the Hologenome Concept.}, journal = {mBio}, volume = {7}, number = {2}, pages = {e01395}, pmid = {27034283}, issn = {2150-7511}, mesh = {Adaptation, Biological ; Animals ; *Biological Evolution ; *Biota ; Humans ; *Microbiota ; Plants ; Recombination, Genetic ; Selection, Genetic ; *Symbiosis ; }, abstract = {The hologenome concept of evolution postulates that the holobiont (host plus symbionts) with its hologenome (host genome plus microbiome) is a level of selection in evolution. Multicellular organisms can no longer be considered individuals by the classical definitions of the term. Every natural animal and plant is a holobiont consisting of the host and diverse symbiotic microbes and viruses. Microbial symbionts can be transmitted from parent to offspring by a variety of methods, including via cytoplasmic inheritance, coprophagy, direct contact during and after birth, and the environment. A large number of studies have demonstrated that these symbionts contribute to the anatomy, physiology, development, innate and adaptive immunity, and behavior and finally also to genetic variation and to the origin and evolution of species. Acquisition of microbes and microbial genes is a powerful mechanism for driving the evolution of complexity. Evolution proceeds both via cooperation and competition, working in parallel.}, } @article {pmid27032420, year = {2017}, author = {Huang, Y and Chen, DH and Liu, BY and Shen, WH and Ruan, Y}, title = {Conservation and diversification of polycomb repressive complex 2 (PRC2) proteins in the green lineage.}, journal = {Briefings in functional genomics}, volume = {16}, number = {2}, pages = {106-119}, doi = {10.1093/bfgp/elw007}, pmid = {27032420}, issn = {2041-2657}, mesh = {*Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Plants/*classification/*metabolism ; Polycomb Repressive Complex 2/genetics/*metabolism ; Protein Interaction Domains and Motifs ; }, abstract = {The polycomb group (PcG) proteins are key epigenetic regulators of gene expression in animals and plants. They act in multiprotein complexes, of which the best characterized is the polycomb repressive complex 2 (PRC2), which catalyses the trimethylation of histone H3 at lysine 27 (H3K27me3) at chromatin targets. In Arabidopsis thaliana, PRC2 proteins are involved in the regulation of diverse developmental processes, including cell fate determination, vegetative growth and development, flowering time control and embryogenesis. Here, we systematically analysed the evolutionary conservation and diversification of PRC2 components in lower and higher plants. We searched for and identified PRC2 homologues from the sequenced genomes of several green lineage species, from the unicellular green alga Ostreococcus lucimarinus to more complicated angiosperms. We found that some PRC2 core components, e.g. E(z), ESC/FIE and MSI/p55, are ancient and have multiplied coincidently with multicellular evolution. For one component, some members are newly formed, especially in the Cruciferae. During evolution, higher plants underwent copy number multiplication of various PRC2 components, which occurred independently for each component, without any obvious co-amplification of PRC2 members. Among the amplified members, usually one was well-conserved and the others were more diversified. Gene amplification occurred at different times for different PcG members during green lineage evolution. Certain PRC2 core components or members of them were highly conserved. Our study provides an insight into the evolutionary conservation and diversification of PcG proteins and may guide future functional characterization of these important epigenetic regulators in plants other than Arabidopsis.}, } @article {pmid27030801, year = {2016}, author = {Panday, A and Grove, A}, title = {The high mobility group protein HMO1 functions as a linker histone in yeast.}, journal = {Epigenetics & chromatin}, volume = {9}, number = {}, pages = {13}, pmid = {27030801}, issn = {1756-8935}, abstract = {BACKGROUND: Eukaryotic chromatin consists of nucleosome core particles connected by linker DNA of variable length. Histone H1 associates with the linker DNA to stabilize the higher-order chromatin structure and to modulate the ability of regulatory factors to access their nucleosomal targets. In Saccharomyces cerevisiae, the protein with greatest sequence similarity to H1 is Hho1p. However, during vegetative growth, hho1∆ cells do not show any discernible cell growth defects or the changes in bulk chromatin structure that are characteristic of chromatin from multicellular eukaryotes in which H1 is depleted. In contrast, the yeast high mobility group (HMGB) protein HMO1 has been reported to compact chromatin, as evidenced by increased nuclease sensitivity in hmo1∆ cells. HMO1 has an unusual domain architecture compared to vertebrate HMGB proteins in that the HMG domains are followed by a lysine-rich extension instead of an acidic domain. We address here the hypothesis that HMO1 serves the role of H1 in terms of chromatin compaction and that this function requires the lysine-rich extension.

RESULTS: We show here that HMO1 fulfills this function of a linker histone. For histone H1, chromatin compaction requires its basic C-terminal domain, and we find that the same pertains to HMO1, as deletion of its C-terminal lysine-rich extension renders chromatin nuclease sensitive. On rDNA, deletion of both HMO1 and Hho1p is required for significantly increased nuclease sensitivity. Expression of human histone H1 completely reverses the nuclease sensitivity characteristic of chromatin isolated from hmo1∆ cells. While chromatin remodeling events associated with repair of DNA double-strand breaks occur faster in the more dynamic chromatin environment created by the hmo1 deletion, expression of human histone H1 results in chromatin remodeling and double-strand break repair similar to that observed in wild-type cells.

CONCLUSION: Our data suggest that S. cerevisiae HMO1 protects linker DNA from nuclease digestion, a property also characteristic of mammalian linker histone H1. Notably, association with HMO1 creates a less dynamic chromatin environment that depends on its lysine-rich domain. That HMO1 has linker histone function has implications for investigations of chromatin structure and function as well as for evolution of proteins with roles in chromatin compaction.}, } @article {pmid27023049, year = {2016}, author = {Roesch, A and Paschen, A and Landsberg, J and Helfrich, I and Becker, JC and Schadendorf, D}, title = {Phenotypic tumour cell plasticity as a resistance mechanism and therapeutic target in melanoma.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {59}, number = {}, pages = {109-112}, doi = {10.1016/j.ejca.2016.02.023}, pmid = {27023049}, issn = {1879-0852}, mesh = {Drug Resistance, Neoplasm/immunology/*physiology ; Epithelial-Mesenchymal Transition/immunology/physiology ; Humans ; Melanoma/*drug therapy/pathology ; Molecular Targeted Therapy/*methods ; Neoplastic Stem Cells/immunology/physiology ; Phenotype ; Tumor Escape/immunology/physiology ; Tumor Microenvironment/immunology/physiology ; }, abstract = {Despite the recent success of MAPK and immune checkpoint inhibitors in advanced melanoma, intrinsic and acquired resistance mechanisms determine the efficacy of these therapeutic approaches. Therapy resistance in melanoma is not solely driven by genetic evolution, but also by epigenetically driven adaptive plasticity. Melanoma cells are shifting between different transcriptional programs, cell cycle states and differentiation phenotypes reflecting a highly dynamic potential to adapt to various exogenous stressors including immune attack or cancer therapies. This review will focus on the dynamic interconversion and overlap between different melanoma cell phenotypes in the context of therapy resistance and a dynamically changing multicellular microenvironment.}, } @article {pmid27021638, year = {2016}, author = {Jubin, T and Kadam, A and Saran, S and Begum, R}, title = {Poly (ADP-ribose) polymerase1 regulates growth and multicellularity in D. discoideum.}, journal = {Differentiation; research in biological diversity}, volume = {92}, number = {1-2}, pages = {10-23}, doi = {10.1016/j.diff.2016.03.002}, pmid = {27021638}, issn = {1432-0436}, mesh = {ADP Ribose Transferases/genetics/*metabolism ; Amino Acid Sequence ; Animals ; Apoptosis ; Blotting, Western ; Cell Cycle ; *Cell Differentiation ; Cells, Cultured ; Dictyostelium/enzymology/*growth & development/metabolism ; *Gene Expression Regulation, Developmental ; Membrane Potential, Mitochondrial ; *Oxidative Stress ; Phylogeny ; Poly (ADP-Ribose) Polymerase-1/genetics/*metabolism ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Amino Acid ; }, abstract = {Poly (ADP-ribose) polymerase (PARP)-1 regulates various biological processes like DNA repair, cell death etc. However, the role of PARP-1 in growth and differentiation still remains elusive. The present study has been undertaken to understand the role of PARP-1 in growth and development of a unicellular eukaryote, Dictyostelium discoideum. In silico analysis demonstrates ADPRT1A as the ortholog of human PARP-1 in D. discoideum. The present study shows that ADPRT1A overexpression (A OE) led to slow growth of D. discoideum and significant population of AOE cells were in S and G2/M phase. Also, AOE cells exhibited high endogenous PARP activity, significant NAD(+) depletion and also significantly lower ADPRT1B and ADPRT2 transcript levels. Moreover, AOE cells are intrinsically stressed and also exhibited susceptibility to oxidative stress. AOE also affected development of D. discoideum predominantly streaming, aggregation and formation of early culminant which are concomitant with reports on PARP's role in D. discoideum development. In addition, under developmental stimuli, increased PARP activity was seen along with developmentally regulated transcript levels of ADPRT1A during D. discoideum multicellularity. Thus the present study suggests that PARP-1 regulates growth as well as the developmental morphogenesis of D. discoideum, thereby opening new avenues to understand the same in higher eukaryotes.}, } @article {pmid26999858, year = {2015}, author = {Titov, VN}, title = {[THE INCONSISTENCIES OF REGULATION OF METABOLISM IN PHYLOGENESIS AT THREE LEVELS OF "RELATIVE BIOLOGICAL PERFECTION": ETIOLOGY OF METABOLIC PANDEMICS].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {60}, number = {11}, pages = {4-12}, pmid = {26999858}, issn = {0869-2084}, mesh = {Adipocytes/classification/metabolism/pathology ; Albumins/metabolism ; Diabetes Mellitus/*epidemiology/genetics/metabolism/pathology ; Essential Hypertension ; Fatty Acids, Nonesterified/metabolism ; Humans ; Hypertension/*epidemiology/genetics/metabolism/pathology ; Insulin/metabolism ; Insulin Resistance ; Macrophages/metabolism/pathology ; Metabolic Networks and Pathways/genetics ; Metabolic Syndrome/*epidemiology/genetics/metabolism/pathology ; Microcirculation/genetics ; Obesity/*epidemiology/genetics/metabolism/pathology ; Organogenesis/genetics ; *Pandemics ; Paracrine Communication/genetics ; *Phylogeny ; }, abstract = {The regulation of metabolism in vivo can be comprehended by considering stages of becoming inphylogenesis of humoral, hormonal, vegetative regulators separately: at the level of cells; in paracrin-regulated cenosises of cells; organs and systems under open blood circulation and closed system of blood flow. The levels of regulations formed at different stages of phylogenesis. Their completion occurred at achievement of "relative biological perfection". Only this way need of cells in functional, structural interaction and forming of multicellular developed. The development of organs and systems of organs also completed at the level of "relative biological perfection". From the same level the third stage of becoming of regulation of metabolism at the level of organism started. When three conditions of "relative biological perfection" achieved consequently at level in vivo are considered in species Homo sapiens using system approach it is detected that "relative biological perfection" in vivo is accompanied by different inconsistencies of regulation of metabolism. They are etiologic factors of "metabolic pandemics ". The inconsistencies (etiological factors) are consider as exemplified by local (at the level of paracrin-regulated cenosises of cells) and system (at the level of organism) regulation of biological reaction metabolism-microcirculation that results in dysfunction of target organs and development of pathogenesis of essential metabolic arterial hypertension. The article describes phylogenetic difference between visceral fatty cells and adpocytes, regulation of metabolism by phylogenetically late insulin, reaction of albumin at increasing of content of unesterified fatty acids in blood plasma, difference of function of resident macrophage and monocytes-macrophages in pathogenesis of atherosclerosis, metabolic syndrome, insulin resistance, obesity, under diabetes mellitus and essential metabolic arterial hypertension.}, } @article {pmid26993504, year = {2016}, author = {D'Asti, E and Chennakrishnaiah, S and Lee, TH and Rak, J}, title = {Extracellular Vesicles in Brain Tumor Progression.}, journal = {Cellular and molecular neurobiology}, volume = {36}, number = {3}, pages = {383-407}, pmid = {26993504}, issn = {1573-6830}, mesh = {Animals ; Brain Neoplasms/diagnosis/genetics/*metabolism/*pathology/therapy ; Cell Communication ; Cell Transformation, Neoplastic/pathology ; *Disease Progression ; Extracellular Vesicles/*metabolism ; Humans ; Mutation/genetics ; }, abstract = {Brain tumors can be viewed as multicellular 'ecosystems' with increasingly recognized cellular complexity and systemic impact. While the emerging diversity of malignant disease entities affecting brain tissues is often described in reference to their signature alterations within the cellular genome and epigenome, arguably these cell-intrinsic changes can be regarded as hardwired adaptations to a variety of cell-extrinsic microenvironmental circumstances. Conversely, oncogenic events influence the microenvironment through their impact on the cellular secretome, including emission of membranous structures known as extracellular vesicles (EVs). EVs serve as unique carriers of bioactive lipids, secretable and non-secretable proteins, mRNA, non-coding RNA, and DNA and constitute pathway(s) of extracellular exit of molecules into the intercellular space, biofluids, and blood. EVs are also highly heterogeneous as reflected in their nomenclature (exosomes, microvesicles, microparticles) attempting to capture their diverse origin, as well as structural, molecular, and functional properties. While EVs may act as a mechanism of molecular expulsion, their non-random uptake by heterologous cellular recipients defines their unique roles in the intercellular communication, horizontal molecular transfer, and biological activity. In the central nervous system, EVs have been implicated as mediators of homeostasis and repair, while in cancer they may act as regulators of cell growth, clonogenicity, angiogenesis, thrombosis, and reciprocal tumor-stromal interactions. EVs produced by specific brain tumor cell types may contain the corresponding oncogenic drivers, such as epidermal growth factor receptor variant III (EGFRvIII) in glioblastoma (and hence are often referred to as 'oncosomes'). Through this mechanism, mutant oncoproteins and nucleic acids may be transferred horizontally between cellular populations altering their individual and collective phenotypes. Oncogenic pathways also impact the emission rates, types, cargo, and biogenesis of EVs, as reflected by preliminary analyses pointing to differences in profiles of EV-regulating genes (vesiculome) between molecular subtypes of glioblastoma, and in other brain tumors. Molecular regulators of vesiculation can also act as oncogenes. These intimate connections suggest the context-specific roles of different EV subsets in the progression of specific brain tumors. Advanced efforts are underway to capture these events through the use of EVs circulating in biofluids as biomarker reservoirs and to guide diagnostic and therapeutic decisions.}, } @article {pmid26990199, year = {2016}, author = {Espinosa, A and Paz-Y-Miño-C, G and Hackey, M and Rutherford, S}, title = {Entamoeba Clone-Recognition Experiments: Morphometrics, Aggregative Behavior, and Cell-Signaling Characterization.}, journal = {The Journal of eukaryotic microbiology}, volume = {63}, number = {3}, pages = {384-393}, pmid = {26990199}, issn = {1550-7408}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/metabolism ; Animals ; Ankyrins/metabolism ; Biological Evolution ; Clone Cells/physiology ; Entamoeba/classification/*genetics/*physiology ; HSP70 Heat-Shock Proteins/metabolism ; Phylogeny ; Protein Kinases/metabolism ; *Signal Transduction ; }, abstract = {Studies on clone- and kin-discrimination in protists have proliferated during the past decade. We report clone-recognition experiments in seven Entamoeba lineages (E. invadens IP-1, E. invadens VK-1:NS, E. terrapinae, E. moshkovskii Laredo, E. moshkovskii Snake, E. histolytica HM-1:IMSS and E. dispar). First, we characterized morphometrically each clone (length, width, and cell-surface area) and documented how they differed statistically from one another (as per single-variable or canonical-discriminant analyses). Second, we demonstrated that amebas themselves could discriminate self (clone) from different (themselves vs. other clones). In mix-cell-line cultures between closely-related (E. invadens IP-1 vs. E. invadens VK-1:NS) or distant-phylogenetic clones (E. terrapinae vs. E. moshkovskii Laredo), amebas consistently aggregated with same-clone members. Third, we identified six putative cell-signals secreted by the amebas (RasGap/Ankyrin, coronin-WD40, actin, protein kinases, heat shock 70, and ubiquitin) and which known functions in Entamoeba spp. included: cell proliferation, cell adhesion, cell movement, and stress-induced encystation. To our knowledge, this is the first multi-clone characterization of Entamoeba spp. morphometrics, aggregative behavior, and cell-signaling secretion in the context of clone-recognition. Protists allow us to study cell-cell recognition from ecological and evolutionary perspectives. Modern protistan lineages can be central to studies about the origins and evolution of multicellularity.}, } @article {pmid26988968, year = {2016}, author = {Hugenholtz, P and Skarshewski, A and Parks, DH}, title = {Genome-Based Microbial Taxonomy Coming of Age.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {8}, number = {6}, pages = {}, pmid = {26988968}, issn = {1943-0264}, mesh = {Animals ; Archaea/genetics ; *Biodiversity ; Biological Evolution ; *Classification ; Genome ; *Genomics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Reconstructing the complete evolutionary history of extant life on our planet will be one of the most fundamental accomplishments of scientific endeavor, akin to the completion of the periodic table, which revolutionized chemistry. The road to this goal is via comparative genomics because genomes are our most comprehensive and objective evolutionary documents. The genomes of plant and animal species have been systematically targeted over the past decade to provide coverage of the tree of life. However, multicellular organisms only emerged in the last 550 million years of more than three billion years of biological evolution and thus comprise a small fraction of total biological diversity. The bulk of biodiversity, both past and present, is microbial. We have only scratched the surface in our understanding of the microbial world, as most microorganisms cannot be readily grown in the laboratory and remain unknown to science. Ground-breaking, culture-independent molecular techniques developed over the past 30 years have opened the door to this so-called microbial dark matter with an accelerating momentum driven by exponential increases in sequencing capacity. We are on the verge of obtaining representative genomes across all life for the first time. However, historical use of morphology, biochemical properties, behavioral traits, and single-marker genes to infer organismal relationships mean that the existing highly incomplete tree is riddled with taxonomic errors. Concerted efforts are now needed to synthesize and integrate the burgeoning genomic data resources into a coherent universal tree of life and genome-based taxonomy.}, } @article {pmid26988136, year = {2016}, author = {Dornbos, SQ and Oji, T and Kanayama, A and Gonchigdorj, S}, title = {A new Burgess Shale-type deposit from the Ediacaran of western Mongolia.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {23438}, pmid = {26988136}, issn = {2045-2322}, mesh = {Animals ; Biological Evolution ; Biota ; Fossils ; Geologic Sediments/*analysis ; Mongolia ; }, abstract = {Preservation of soft-bodied organisms is exceedingly rare in the fossil record. One way that such fossils are preserved is as carbonaceous compressions in fined-grained marine sedimentary rocks. These deposits of exceptional preservation are known as Burgess Shale-type (BST) deposits. During the Cambrian Period, BST deposits are more common and provide a crucial view of early animal evolution. The earliest definitive fossil evidence for macroscopic animal-grade organisms is found in the preceding Ediacaran Period. BST deposits from the Ediacaran are rarer and lack conclusive evidence for animals. Here we report the discovery of a new Ediacaran BST deposit with exceptional preservation of non-mineralizing macro-organisms in thinly bedded black shale from Zavkhan Province, western Mongolia. This fossil assemblage, here named the Zuun-Arts biota, currently consists of two new species of probable macroscopic multicellular benthic algae. One species, Chinggiskhaania bifurcata n. gen., n. sp., dominates the biota. The other species, Zuunartsphyton delicatum n. gen., n. sp., is known from three specimens. SEM-EDS analysis shows that the fossils are composed of aluminosilicate clay minerals and some carbon, a composition comparable to fossils from the Cambrian Burgess Shale biota. This discovery opens a new window through which to view late Precambrian life.}, } @article {pmid26987708, year = {2016}, author = {Rensing, SA}, title = {(Why) Does Evolution Favour Embryogenesis?.}, journal = {Trends in plant science}, volume = {21}, number = {7}, pages = {562-573}, doi = {10.1016/j.tplants.2016.02.004}, pmid = {26987708}, issn = {1878-4372}, mesh = {*Biological Evolution ; Embryonic Development/*physiology ; Phaeophyta/physiology ; Plants/metabolism ; }, abstract = {Complex multicellular organisms typically possess life cycles in which zygotes (formed by gamete fusion) and meiosis occur. Canonical animal embryogenesis describes development from zygote to birth. It involves polarisation of the egg/zygote, asymmetric cell divisions, establishment of axes, symmetry breaking, formation of organs, and parental nutrition (at least in early stages). Similar developmental patterns have independently evolved in other eukaryotic lineages, including land plants and brown algae. The question arises whether embryo-like structures and associated developmental processes recurrently emerge because they are local optima of the evolutionary landscape. To understand which evolutionary principles govern complex multicellularity, we need to analyse why and how similar processes evolve convergently - von Baer's and Haeckel's phylotypic stage revisited in other phyla.}, } @article {pmid26986966, year = {2016}, author = {Jaiteh, M and Taly, A and Hénin, J}, title = {Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors.}, journal = {PloS one}, volume = {11}, number = {3}, pages = {e0151934}, pmid = {26986966}, issn = {1932-6203}, mesh = {Animals ; Archaea/classification/genetics/physiology ; Conserved Sequence/genetics/physiology ; Cysteine Loop Ligand-Gated Ion Channel Receptors/genetics/physiology ; Eukaryota/genetics/physiology ; Evolution, Molecular ; Fungi/genetics/physiology ; Invertebrates/genetics/physiology ; Ligand-Gated Ion Channels/*genetics/physiology ; Phylogeny ; Plants/genetics ; Receptors, Neurotransmitter/*genetics/physiology ; Sequence Alignment ; }, abstract = {Pentameric ligand-gated ion channels (pLGICs) are ubiquitous neurotransmitter receptors in Bilateria, with a small number of known prokaryotic homologues. Here we describe a new inventory and phylogenetic analysis of pLGIC genes across all kingdoms of life. Our main finding is a set of pLGIC genes in unicellular eukaryotes, some of which are metazoan-like Cys-loop receptors, and others devoid of Cys-loop cysteines, like their prokaryotic relatives. A number of such "Cys-less" receptors also appears in invertebrate metazoans. Together, those findings draw a new distribution of pLGICs in eukaryotes. A broader distribution of prokaryotic channels also emerges, including a major new archaeal taxon, Thaumarchaeota. More generally, pLGICs now appear nearly ubiquitous in major taxonomic groups except multicellular plants and fungi. However, pLGICs are sparsely present in unicellular taxa, suggesting a high rate of gene loss and a non-essential character, contrasting with their essential role as synaptic receptors of the bilaterian nervous system. Multiple alignments of these highly divergent sequences reveal a small number of conserved residues clustered at the interface between the extracellular and transmembrane domains. Only the "Cys-loop" proline is absolutely conserved, suggesting the more fitting name "Pro loop" for that motif, and "Pro-loop receptors" for the superfamily. The infered molecular phylogeny shows a Cys-loop and a Cys-less clade in eukaryotes, both containing metazoans and unicellular members. This suggests new hypotheses on the evolutionary history of the superfamily, such as a possible origin of the Cys-loop cysteines in an ancient unicellular eukaryote. Deeper phylogenetic relationships remain uncertain, particularly around the split between bacteria, archaea, and eukaryotes.}, } @article {pmid26986787, year = {2015}, author = {Qiu, H and Price, DC and Yang, EC and Yoon, HS and Bhattacharya, D}, title = {Evidence of ancient genome reduction in red algae (Rhodophyta).}, journal = {Journal of phycology}, volume = {51}, number = {4}, pages = {624-636}, doi = {10.1111/jpy.12294}, pmid = {26986787}, issn = {1529-8817}, abstract = {Red algae (Rhodophyta) comprise a monophyletic eukaryotic lineage of ~6,500 species with a fossil record that extends back 1.2 billion years. A surprising aspect of red algal evolution is that sequenced genomes encode a relatively limited gene inventory (~5-10 thousand genes) when compared with other free-living algae or to other eukaryotes. This suggests that the common ancestor of red algae may have undergone extensive genome reduction, which can result from lineage specialization to a symbiotic or parasitic lifestyle or adaptation to an extreme or oligotrophic environment. We gathered genome and transcriptome data from a total of 14 red algal genera that represent the major branches of this phylum to study genome evolution in Rhodophyta. Analysis of orthologous gene gains and losses identifies two putative major phases of genome reduction: (i) in the stem lineage leading to all red algae resulting in the loss of major functions such as flagellae and basal bodies, the glycosyl-phosphatidylinositol anchor biosynthesis pathway, and the autophagy regulation pathway; and (ii) in the common ancestor of the extremophilic Cyanidiophytina. Red algal genomes are also characterized by the recruitment of hundreds of bacterial genes through horizontal gene transfer that have taken on multiple functions in shared pathways and have replaced eukaryotic gene homologs. Our results suggest that Rhodophyta may trace their origin to a gene depauperate ancestor. Unlike plants, it appears that a limited gene inventory is sufficient to support the diversification of a major eukaryote lineage that possesses sophisticated multicellular reproductive structures and an elaborate triphasic sexual cycle.}, } @article {pmid26973658, year = {2016}, author = {Rahman, H and Yang, J and Xu, YP and Munyampundu, JP and Cai, XZ}, title = {Phylogeny of Plant CAMTAs and Role of AtCAMTAs in Nonhost Resistance to Xanthomonas oryzae pv. oryzae.}, journal = {Frontiers in plant science}, volume = {7}, number = {}, pages = {177}, pmid = {26973658}, issn = {1664-462X}, abstract = {Calmodulin-binding transcription activator (CAMTA) constitutes one of the most important Ca(2+)/CaM-regulated transcription factor families in plants. Nevertheless, the phylogeny, protein interaction network, and role in nonhost resistance of plant CAMTAs are not well understood. In this study, 200 CAMTA genes were identified from 35 species representing four major plant lineages. The CAMTA genes were conserved in multicellular land plants but absent in unicellular eukaryotes, and were likely to emerge from the fusion of two separate genes encoding a CAMTA-like protein and an IQ/CaM binding motif containing protein, respectively, in the embryophyta lineage ancestor. Approximately one fourth of plant CAMTAs did not contain a TIG domain. This non-TIG class of CAMTAs seems to have newly evolved through mutation of some key amino acids in the TIG domain of flowering land plants after divergence from the non-flowering plants. Phylogenetic analysis classified CAMTA proteins into three major groups and nine distinct subgroups, a result supported by protein domain and motif conservation analyses. Most (59.0 and 21.5%) of the identified CAMTA genes contained 12 or 11 introns, respectively. Gene duplication, intron invasion, enlargement and turnover, as well as exon rearrangements and skipping have apparently occurred during evolution of the CAMTA family. Moreover, 38 potential interactors of six Arabidopsis CAMTAs were predicted and 10 predicted target genes of AtCAMTA3 exhibited changes in expression between Atcamta3 mutants and wild-type plants. The majority of predicted interactors are transcription factors and/or Ca(2+)/CaM-regulated proteins, suggesting that transcriptional regulation of the target genes might be the dominant functional mechanism of AtCAMTAs, and AtCAMTAs might act together with other Ca(2+) signaling components to regulate Ca(2+)-related biological processes. Furthermore, functional analyses employing Atcamta mutants revealed that AtCAMTA3 negatively regulated the immunity triggered by flg22 and nonhost resistance to Xanthomonas oryzae pv. oryzae via repressing accumulation of reactive oxygen species probably by targeting CBP60G, EDS1, and NDR1 and involving SA pathway.}, } @article {pmid26970004, year = {2016}, author = {Woodland, HR}, title = {The Birth of Animal Development: Multicellularity and the Germline.}, journal = {Current topics in developmental biology}, volume = {117}, number = {}, pages = {609-630}, doi = {10.1016/bs.ctdb.2015.10.020}, pmid = {26970004}, issn = {1557-8933}, mesh = {Animals ; *Biological Evolution ; Germ Cells/*cytology ; Reproduction/*physiology ; }, abstract = {The evolution of multicellular animals has been attributed to many kinds of selective advantage; here I suggest that the evolution of somatic cells to feed and protect the germline was central to the appearance of animals. This would have been driven by selection for extreme anisogamy--the evolution of sperm and egg. Evidence is adduced from the germline stem cells of simple animals (defining germline as any cell that normally produces the next generation via the sexual process) and from the control circuitry ubiquitous in animal germlines. With the soma and its elaboration came animal development, as we understand it.}, } @article {pmid26967282, year = {2016}, author = {Stoeger, T and Battich, N and Pelkmans, L}, title = {Passive Noise Filtering by Cellular Compartmentalization.}, journal = {Cell}, volume = {164}, number = {6}, pages = {1151-1161}, doi = {10.1016/j.cell.2016.02.005}, pmid = {26967282}, issn = {1097-4172}, mesh = {Animals ; Cell Nucleus/physiology ; *Cell Physiological Phenomena ; Feedback ; Humans ; Intracellular Membranes/*physiology ; Single-Cell Analysis ; *Stochastic Processes ; }, abstract = {Chemical reactions contain an inherent element of randomness, which presents itself as noise that interferes with cellular processes and communication. Here we discuss the ability of the spatial partitioning of molecular systems to filter and, thus, remove noise, while preserving regulated and predictable differences between single living cells. In contrast to active noise filtering by network motifs, cellular compartmentalization is highly effective and easily scales to numerous systems without requiring a substantial usage of cellular energy. We will use passive noise filtering by the eukaryotic cell nucleus as an example of how this increases predictability of transcriptional output, with possible implications for the evolution of complex multicellularity.}, } @article {pmid26961431, year = {2016}, author = {Morrill, GA and Kostellow, AB and Liu, L and Gupta, RK and Askari, A}, title = {Evolution of the α-Subunit of Na/K-ATPase from Paramecium to Homo sapiens: Invariance of Transmembrane Helix Topology.}, journal = {Journal of molecular evolution}, volume = {82}, number = {4-5}, pages = {183-198}, pmid = {26961431}, issn = {1432-1432}, support = {P01 HL036573/HL/NHLBI NIH HHS/United States ; R01 GM071324/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Binding Sites ; Biological Evolution ; Cell Membrane/metabolism ; *Evolution, Molecular ; Humans ; Molecular Sequence Data ; Protein Conformation, alpha-Helical/physiology ; Sodium/metabolism ; Sodium-Potassium-Exchanging ATPase/*genetics/metabolism ; }, abstract = {Na/K-ATPase is a key plasma membrane enzyme involved in cell signaling, volume regulation, and maintenance of electrochemical gradients. The α-subunit, central to these functions, belongs to a large family of P-type ATPases. Differences in transmembrane (TM) helix topology, sequence homology, helix-helix contacts, cell signaling, and protein domains of Na/K-ATPase α-subunit were compared in fungi (Beauveria), unicellular organisms (Paramecia), primitive multicellular organisms (Hydra), and vertebrates (Xenopus, Homo sapiens), and correlated with evolution of physiological functions in the α-subunit. All α-subunits are of similar length, with groupings of four and six helices in the N- and C-terminal regions, respectively. Minimal homology was seen for protein domain patterns in Paramecium and Hydra, with high correlation between Hydra and vertebrates. Paramecium α-subunits display extensive disorder, with minimal helix contacts. Increases in helix contacts in Hydra approached vertebrates. Protein motifs known to be associated with membrane lipid rafts and cell signaling reveal significant positional shifts between Paramecium and Hydra vulgaris, indicating that regional membrane fluidity changes occur during evolution. Putative steroid binding sites overlapping TM-3 occurred in all species. Sites associated with G-protein-receptor stimulation occur both in vertebrates and amphibia but not in Hydra or Paramecia. The C-terminus moiety "KETYY," necessary for the Na(+) activation of pump phosphorylation, is not present in unicellular species indicating the absence of classical Na(+)/K(+)-pumps. The basic protein topology evolved earliest, followed by increases in protein domains and ordered helical arrays, correlated with appearance of α-subunit regions known to involve cell signaling, membrane recycling, and ion channel formation.}, } @article {pmid26958911, year = {2015}, author = {Zwart, MP and Elena, SF}, title = {Matters of Size: Genetic Bottlenecks in Virus Infection and Their Potential Impact on Evolution.}, journal = {Annual review of virology}, volume = {2}, number = {1}, pages = {161-179}, doi = {10.1146/annurev-virology-100114-055135}, pmid = {26958911}, issn = {2327-0578}, mesh = {Animals ; *Biological Evolution ; *Genome Size ; Humans ; Virus Diseases/*virology ; Virus Physiological Phenomena ; Viruses/classification/*genetics/isolation & purification ; }, abstract = {For virus infections of multicellular hosts, narrow genetic bottlenecks during transmission and within-host spread appear to be widespread. These bottlenecks will affect the maintenance of genetic variation in a virus population and the prevalence of mixed-strain infections, thereby ultimately determining the strength with which different random forces act during evolution. Here we consider different approaches for estimating bottleneck sizes and weigh their merits. We then review quantitative estimates of bottleneck size during cellular infection, within-host spread, horizontal transmission, and finally vertical transmission. In most cases we find that bottlenecks do regularly occur, although in many cases they appear to be virion-concentration dependent. Finally, we consider the evolutionary implications of genetic bottlenecks during virus infection. Although on average strong bottlenecks will lead to declines in fitness, we consider a number of scenarios in which bottlenecks could also be advantageous for viruses.}, } @article {pmid26945503, year = {2016}, author = {Song, C and Kidarsa, TA and van de Mortel, JE and Loper, JE and Raaijmakers, JM}, title = {Living on the edge: emergence of spontaneous gac mutations in Pseudomonas protegens during swarming motility.}, journal = {Environmental microbiology}, volume = {18}, number = {10}, pages = {3453-3465}, doi = {10.1111/1462-2920.13288}, pmid = {26945503}, issn = {1462-2920}, mesh = {Bacterial Proteins/*genetics/metabolism ; Chemotaxis ; Flagella/genetics/metabolism ; Gene Expression Profiling ; *Mutation ; Pseudomonas/*cytology/genetics/*metabolism ; }, abstract = {Swarming motility is a flagella-driven multicellular behaviour that allows bacteria to colonize new niches and escape competition. Here, we investigated the evolution of specific mutations in the GacS/GacA two-component regulatory system in swarming colonies of Pseudomonas protegens Pf-5. Experimental evolution assays showed that repeated rounds of swarming by wildtype Pf-5 drives the accumulation of gacS/gacA spontaneous mutants on the swarming edge. These mutants cannot swarm on their own because they lack production of the biosurfactant orfamide A, but they do co-swarm with orfamide-producing wildtype Pf-5. These co-swarming assays further demonstrated that ΔgacA mutant cells indeed predominate on the edge and that initial ΔgacA:wildtype Pf-5 ratios of at least 2:1 lead to a collapse of the swarming colony. Subsequent whole-genome transcriptome analyses revealed that genes associated with motility, resource acquisition, chemotaxis and efflux were significantly upregulated in ΔgacA mutant on swarming medium. Moreover, transmission electron microscopy showed that ΔgacA mutant cells were longer and more flagellated than wildtype cells, which may explain their predominance on the swarming edge. We postulate that adaptive evolution through point mutations is a common feature of range-expanding microbial populations and that the putative fitness benefits of these mutations during dispersal of bacteria into new territories are frequency-dependent.}, } @article {pmid26941230, year = {2016}, author = {Reyes-Bermudez, A and Villar-Briones, A and Ramirez-Portilla, C and Hidaka, M and Mikheyev, AS}, title = {Developmental Progression in the Coral Acropora digitifera Is Controlled by Differential Expression of Distinct Regulatory Gene Networks.}, journal = {Genome biology and evolution}, volume = {8}, number = {3}, pages = {851-870}, pmid = {26941230}, issn = {1759-6653}, mesh = {Animals ; Anthozoa/*genetics/growth & development ; Cell Differentiation/genetics ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks/*genetics ; Larva/*genetics/growth & development ; Transcriptome/*genetics ; }, abstract = {Corals belong to the most basal class of the Phylum Cnidaria, which is considered the sister group of bilaterian animals, and thus have become an emerging model to study the evolution of developmental mechanisms. Although cell renewal, differentiation, and maintenance of pluripotency are cellular events shared by multicellular animals, the cellular basis of these fundamental biological processes are still poorly understood. To understand how changes in gene expression regulate morphogenetic transitions at the base of the eumetazoa, we performed quantitative RNA-seq analysis duringAcropora digitifera's development. We collected embryonic, larval, and adult samples to characterize stage-specific transcription profiles, as well as broad expression patterns. Transcription profiles reconstructed development revealing two main expression clusters. The first cluster grouped blastula and gastrula and the second grouped subsequent developmental time points. Consistently, we observed clear differences in gene expression between early and late developmental transitions, with higher numbers of differentially expressed genes and fold changes around gastrulation. Furthermore, we identified three coexpression clusters that represented discrete gene expression patterns. During early transitions, transcriptional networks seemed to regulate cellular fate and morphogenesis of the larval body. In late transitions, these networks seemed to play important roles preparing planulae for switch in lifestyle and regulation of adult processes. Although developmental progression inA. digitiferais regulated to some extent by differential coexpression of well-defined gene networks, stage-specific transcription profiles appear to be independent entities. While negative regulation of transcription is predominant in early development, cell differentiation was upregulated in larval and adult stages.}, } @article {pmid26940948, year = {2016}, author = {Tice, AK and Silberman, JD and Walthall, AC and Le, KN and Spiegel, FW and Brown, MW}, title = {Sorodiplophrys stercorea: Another Novel Lineage of Sorocarpic Multicellularity.}, journal = {The Journal of eukaryotic microbiology}, volume = {63}, number = {5}, pages = {623-628}, doi = {10.1111/jeu.12311}, pmid = {26940948}, issn = {1550-7408}, mesh = {Animals ; Base Sequence ; Cattle/parasitology ; DNA, Protozoan/isolation & purification ; DNA, Ribosomal ; Genes, rRNA/genetics ; Horses/parasitology ; Mississippi ; *Phylogeny ; Rhizaria/classification ; Stramenopiles/*classification/cytology/genetics/*isolation & purification ; }, abstract = {Sorodiplophrys stercorea is a sorocarpic organism that utilizes filose pseudopodia for locomotion and absorptive nutrition. It has traditionally been considered to be a member of the Labyrinthulae based on its morphology. Its closest relatives were thought to be species in the taxon Diplophrys. Since the genus Diplophrys has been shown to be paraphyletic and S. stercorea has pseudopodia similar to some members of Rhizaria, we examined its relationship with other eukaryotes. We obtained four isolates from the dung of cow and horse, brought each into monoeukaryotic culture, and sequenced their SSU rRNA gene for phylogenetic analysis. All our isolates were shown to form a monophyletic group in the Labyrinthulae, nested in the Amphifiloidea clade. Our results demonstrate that Sorodiplophrys is more closely related to species of the genus Amphifila than to Diplophrys and represents an additional independent origin of sorocarpic multicellularity among eukaryotes. This study represents the first confirmed sorocarpic lifestyle in the Stramenopiles.}, } @article {pmid26933058, year = {2016}, author = {Singletary, LA and Karlinsey, JE and Libby, SJ and Mooney, JP and Lokken, KL and Tsolis, RM and Byndloss, MX and Hirao, LA and Gaulke, CA and Crawford, RW and Dandekar, S and Kingsley, RA and Msefula, CL and Heyderman, RS and Fang, FC}, title = {Loss of Multicellular Behavior in Epidemic African Nontyphoidal Salmonella enterica Serovar Typhimurium ST313 Strain D23580.}, journal = {mBio}, volume = {7}, number = {2}, pages = {e02265}, pmid = {26933058}, issn = {2150-7511}, support = {U19 AI090882/AI/NIAID NIH HHS/United States ; T32 AI060555/AI/NIAID NIH HHS/United States ; R01 AI112640/AI/NIAID NIH HHS/United States ; AI91966/AI/NIAID NIH HHS/United States ; R56 AI098078/AI/NIAID NIH HHS/United States ; R01 AI098078/AI/NIAID NIH HHS/United States ; AI44486/AI/NIAID NIH HHS/United States ; T32AI60555/AI/NIAID NIH HHS/United States ; AI90882/AI/NIAID NIH HHS/United States ; AI1112640/AI/NIAID NIH HHS/United States ; AI43274/AI/NIAID NIH HHS/United States ; R01 AI044486/AI/NIAID NIH HHS/United States ; R01 AI043274/AI/NIAID NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; AI98078/AI/NIAID NIH HHS/United States ; }, mesh = {*Adaptation, Biological ; Africa South of the Sahara/epidemiology ; Animals ; Catalase/genetics/metabolism ; Disease Models, Animal ; Epidemics ; Glucosyltransferases/genetics/metabolism ; Humans ; Macaca mulatta ; Mice ; Mutant Proteins/genetics/metabolism ; Salmonella Infections/epidemiology/*microbiology ; Salmonella typhimurium/*enzymology/genetics/isolation & purification/*physiology ; *Stress, Physiological ; }, abstract = {UNLABELLED: Nontyphoidal Salmonella enterica serovar Typhimurium is a frequent cause of bloodstream infections in children and HIV-infected adults in sub-Saharan Africa. Most isolates from African patients with bacteremia belong to a single sequence type, ST313, which is genetically distinct from gastroenteritis-associated ST19 strains, such as 14028s and SL1344. Some studies suggest that the rapid spread of ST313 across sub-Saharan Africa has been facilitated by anthroponotic (person-to-person) transmission, eliminating the need for Salmonella survival outside the host. While these studies have not ruled out zoonotic or other means of transmission, the anthroponotic hypothesis is supported by evidence of extensive genomic decay, a hallmark of host adaptation, in the sequenced ST313 strain D23580. We have identified and demonstrated 2 loss-of-function mutations in D23580, not present in the ST19 strain 14028s, that impair multicellular stress resistance associated with survival outside the host. These mutations result in inactivation of the KatE stationary-phase catalase that protects high-density bacterial communities from oxidative stress and the BcsG cellulose biosynthetic enzyme required for the RDAR (red, dry, and rough) colonial phenotype. However, we found that like 14028s, D23580 is able to elicit an acute inflammatory response and cause enteritis in mice and rhesus macaque monkeys. Collectively, these observations suggest that African S. Typhimurium ST313 strain D23580 is becoming adapted to an anthroponotic mode of transmission while retaining the ability to infect and cause enteritis in multiple host species.

IMPORTANCE: The last 3 decades have witnessed an epidemic of invasive nontyphoidal Salmonella infections in sub-Saharan Africa. Genomic analysis and clinical observations suggest that the Salmonella strains responsible for these infections are evolving to become more typhoid-like with regard to patterns of transmission and virulence. This study shows that a prototypical African nontyphoidal Salmonella strain has lost traits required for environmental stress resistance, consistent with an adaptation to a human-to-human mode of transmission. However, in contrast to predictions, the strain remains capable of causing acute inflammation in the mammalian intestine. This suggests that the systemic clinical presentation of invasive nontyphoidal Salmonella infections in Africa reflects the immune status of infected hosts rather than intrinsic differences in the virulence of African Salmonella strains. Our study provides important new insights into the evolution of host adaptation in bacterial pathogens.}, } @article {pmid26932355, year = {2016}, author = {Luo, T and He, X and Xing, K}, title = {Lineage analysis by microsatellite loci deep sequencing in mice.}, journal = {Molecular reproduction and development}, volume = {83}, number = {5}, pages = {387-391}, doi = {10.1002/mrd.22632}, pmid = {26932355}, issn = {1098-2795}, mesh = {Animals ; Female ; *Genetic Loci ; Genome-Wide Association Study ; *High-Throughput Nucleotide Sequencing ; Male ; Mice ; *Microsatellite Repeats ; }, abstract = {Lineage analysis is the identification of all the progeny of a single progenitor cell, and has become particularly useful for studying developmental processes and cancer biology. Here, we propose a novel and effective method for lineage analysis that combines sequence capture and next-generation sequencing technology. Genome-wide mononucleotide and dinucleotide microsatellite loci in eight samples from two mice were identified and used to construct phylogenetic trees based on somatic indel mutations at these loci, which were unique enough to distinguish and parse samples from different mice into different groups along the lineage tree. For example, biopsies from the liver and stomach, which originate from the endoderm, were located in the same clade, while samples in kidney, which originate from the mesoderm, were located in another clade. Yet, tissue with a common developmental origin may still contain cells of a mixed ancestry. This genome-wide approach thus provides a non-invasive lineage analysis method based on mutations that accumulate in the genomes of opaque multicellular organism somatic cells. Mol. Reprod. Dev. 83: 387-391, 2016. © 2016 Wiley Periodicals, Inc.}, } @article {pmid26931797, year = {2016}, author = {Smith, J and Strassmann, JE and Queller, DC}, title = {Fine-scale spatial ecology drives kin selection relatedness among cooperating amoebae.}, journal = {Evolution; international journal of organic evolution}, volume = {70}, number = {4}, pages = {848-859}, doi = {10.1111/evo.12895}, pmid = {26931797}, issn = {1558-5646}, mesh = {Dictyostelium/*genetics/physiology ; Ecology ; Genotype ; *Microbial Interactions ; Population Density ; *Selection, Genetic ; Soil Microbiology ; }, abstract = {Cooperation among microbes is important for traits as diverse as antibiotic resistance, pathogen virulence, and sporulation. The evolutionary stability of cooperation against "cheater" mutants depends critically on the extent to which microbes interact with genetically similar individuals. The causes of this genetic social structure in natural microbial systems, however, are unknown. Here, we show that social structure among cooperative Dictyostelium amoebae is driven by the population ecology of colonization, growth, and dispersal acting at spatial scales as small as fruiting bodies themselves. Despite the fact that amoebae disperse while grazing, all it takes to create substantial genetic clonality within multicellular fruiting bodies is a few millimeters distance between the cells colonizing a feeding site. Even adjacent fruiting bodies can consist of different genotypes. Soil populations of amoebae are sparse and patchily distributed at millimeter scales. The fine-scale spatial structure of cells and genotypes can thus account for the otherwise unexplained high genetic uniformity of spores in fruiting bodies from natural substrates. These results show how a full understanding of microbial cooperation requires understanding ecology and social structure at the small spatial scales microbes themselves experience.}, } @article {pmid26931578, year = {2016}, author = {Zaccard, CR and Rinaldo, CR and Mailliard, RB}, title = {Linked in: immunologic membrane nanotube networks.}, journal = {Journal of leukocyte biology}, volume = {100}, number = {1}, pages = {81-94}, pmid = {26931578}, issn = {1938-3673}, support = {S10 OD010625/OD/NIH HHS/United States ; R37 AI041870/AI/NIAID NIH HHS/United States ; U01 AI035041/AI/NIAID NIH HHS/United States ; UM1 AI035043/AI/NIAID NIH HHS/United States ; T32 AI065380/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigen Presentation/*immunology ; Cell Membrane/*immunology ; Dendritic Cells/*immunology ; Humans ; Immunity, Cellular/*immunology ; *Nanotubes ; }, abstract = {Membrane nanotubes, also termed tunneling nanotubes, are F-actin-based structures that can form direct cytoplasmic connections and support rapid communication between distant cells. These nanoscale conduits have been observed in diverse cell types, including immune, neuronal, stromal, cancer, and stem cells. Until recently, little was known about the mechanisms involved in membrane nanotube development in myeloid origin APCs or how membrane nanotube networks support their ability to bridge innate and adaptive immunity. New research has provided insight into the modes of induction and regulation of the immune process of "reticulation" or the development of multicellular membrane nanotube networks in dendritic cells. Preprogramming by acute type 1 inflammatory mediators at their immature stage licenses mature type 1-polarized dendritic cells to reticulate upon subsequent interaction with CD40 ligand-expressing CD4(+) Th cells. Dendritic cell reticulation can support direct antigen transfer for amplification of specific T cell responses and can be positively or negatively regulated by signals from distinct Th cell subsets. Membrane nanotubes not only enhance the ability of immature dendritic cells to sense pathogens and rapidly mobilize nearby antigen-presenting cells in the peripheral tissues but also likely support communication of pathogen-related information from mature migratory dendritic cells to resident dendritic cells in lymph nodes. Therefore, the reticulation process facilitates a coordinated multicellular response for the efficient initiation of cell-mediated adaptive immune responses. Herein, we discuss studies focused on the molecular mechanisms of membrane nanotube formation, structure, and function in the context of immunity and how pathogens, such as HIV-1, may use dendritic cell reticulation to circumvent host defenses.}, } @article {pmid26927887, year = {2016}, author = {Zhang, X and Zhuchenko, O and Kuspa, A and Soldati, T}, title = {Social amoebae trap and kill bacteria by casting DNA nets.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {10938}, pmid = {26927887}, issn = {2041-1723}, support = {P01 HD039691/HD/NICHD NIH HHS/United States ; HD39691/HD/NICHD NIH HHS/United States ; }, mesh = {Bacteria ; DNA/*physiology ; Dictyostelium/*physiology ; Extracellular Traps/*physiology ; Klebsiella pneumoniae/*physiology ; *Microbial Viability ; Pseudomonas aeruginosa/*physiology ; Reactive Oxygen Species ; }, abstract = {Extracellular traps (ETs) from neutrophils are reticulated nets of DNA decorated with anti-microbial granules, and are capable of trapping and killing extracellular pathogens. Various phagocytes of mammals and invertebrates produce ETs, however, the evolutionary history of this DNA-based host defence strategy is unclear. Here we report that Sentinel (S) cells of the multicellular slug stage of the social amoeba Dictyostelium discoideum produce ETs upon stimulation with bacteria or lipopolysaccharide in a reactive oxygen species-dependent manner. The production of ETs by S cells requires a Toll/Interleukin-1 receptor domain-containing protein TirA and reactive oxygen species-generating NADPH oxidases. Disruption of these genes results in decreased clearance of bacterial infections. Our results demonstrate that D. discoideum is a powerful model organism to study the evolution and conservation of mechanisms of cell-intrinsic immunity, and suggest that the origin of DNA-based ETs as an innate immune defence predates the emergence of metazoans.}, } @article {pmid26925779, year = {2016}, author = {Mohanty, S and Oruganty, K and Kwon, A and Byrne, DP and Ferries, S and Ruan, Z and Hanold, LE and Katiyar, S and Kennedy, EJ and Eyers, PA and Kannan, N}, title = {Hydrophobic Core Variations Provide a Structural Framework for Tyrosine Kinase Evolution and Functional Specialization.}, journal = {PLoS genetics}, volume = {12}, number = {2}, pages = {e1005885}, pmid = {26925779}, issn = {1553-7404}, support = {R01 GM114409/GM/NIGMS NIH HHS/United States ; R03 CA188439/CA/NCI NIH HHS/United States ; GM114409-01/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Aurora Kinase A/chemistry/genetics/metabolism ; Catalytic Domain ; Conserved Sequence ; *Evolution, Molecular ; Hydrophobic and Hydrophilic Interactions ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Mutation ; Protein Kinase Inhibitors/pharmacology ; Protein Serine-Threonine Kinases/chemistry/metabolism ; Protein-Tyrosine Kinases/antagonists & inhibitors/*chemistry/genetics/*metabolism ; Receptor Protein-Tyrosine Kinases/chemistry/genetics/metabolism ; Receptor, EphA3 ; Structure-Activity Relationship ; }, abstract = {Protein tyrosine kinases (PTKs) are a group of closely related enzymes that have evolutionarily diverged from serine/threonine kinases (STKs) to regulate pathways associated with multi-cellularity. Evolutionary divergence of PTKs from STKs has occurred through accumulation of mutations in the active site as well as in the commonly conserved hydrophobic core. While the functional significance of active site variations is well understood, relatively little is known about how hydrophobic core variations contribute to PTK evolutionary divergence. Here, using a combination of statistical sequence comparisons, molecular dynamics simulations, mutational analysis and in vitro thermostability and kinase assays, we investigate the structural and functional significance of key PTK-specific variations in the kinase core. We find that the nature of residues and interactions in the hydrophobic core of PTKs is strikingly different from other protein kinases, and PTK-specific variations in the core contribute to functional divergence by altering the stability and dynamics of the kinase domain. In particular, a functionally critical STK-conserved histidine that stabilizes the regulatory spine in STKs is selectively mutated to an alanine, serine or glutamate in PTKs, and this loss-of-function mutation is accommodated, in part, through compensatory PTK-specific interactions in the core. In particular, a PTK-conserved phenylalanine in the I-helix appears to structurally and functionally compensate for the loss of STK-histidine by interacting with the regulatory spine, which has far-reaching effects on enzyme activity, inhibitor sensing, and stability. We propose that hydrophobic core variations provide a selective advantage during PTK evolution by increasing the conformational flexibility, and therefore the allosteric potential of the kinase domain. Our studies also suggest that Tyrosine Kinase Like kinases such as RAF are intermediates in PTK evolutionary divergence inasmuch as they share features of both PTKs and STKs in the core. Finally, our studies provide an evolutionary framework for identifying and characterizing disease and drug resistance mutations in the kinase core.}, } @article {pmid26924853, year = {2015}, author = {Schirrmeister, BE and Gugger, M and Donoghue, PC}, title = {Cyanobacteria and the Great Oxidation Event: evidence from genes and fossils.}, journal = {Palaeontology}, volume = {58}, number = {5}, pages = {769-785}, pmid = {26924853}, issn = {0031-0239}, support = {BB/G006660/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J00538X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Cyanobacteria are among the most ancient of evolutionary lineages, oxygenic photosynthesizers that may have originated before 3.0 Ga, as evidenced by free oxygen levels. Throughout the Precambrian, cyanobacteria were one of the most important drivers of biological innovations, strongly impacting early Earth's environments. At the end of the Archean Eon, they were responsible for the rapid oxygenation of Earth's atmosphere during an episode referred to as the Great Oxidation Event (GOE). However, little is known about the origin and diversity of early cyanobacterial taxa, due to: (1) the scarceness of Precambrian fossil deposits; (2) limited characteristics for the identification of taxa; and (3) the poor preservation of ancient microfossils. Previous studies based on 16S rRNA have suggested that the origin of multicellularity within cyanobacteria might have been associated with the GOE. However, single-gene analyses have limitations, particularly for deep branches. We reconstructed the evolutionary history of cyanobacteria using genome scale data and re-evaluated the Precambrian fossil record to get more precise calibrations for a relaxed clock analysis. For the phylogenomic reconstructions, we identified 756 conserved gene sequences in 65 cyanobacterial taxa, of which eight genomes have been sequenced in this study. Character state reconstructions based on maximum likelihood and Bayesian phylogenetic inference confirm previous findings, of an ancient multicellular cyanobacterial lineage ancestral to the majority of modern cyanobacteria. Relaxed clock analyses provide firm support for an origin of cyanobacteria in the Archean and a transition to multicellularity before the GOE. It is likely that multicellularity had a greater impact on cyanobacterial fitness and thus abundance, than previously assumed. Multicellularity, as a major evolutionary innovation, forming a novel unit for selection to act upon, may have served to overcome evolutionary constraints and enabled diversification of the variety of morphotypes seen in cyanobacteria today.}, } @article {pmid26923142, year = {2016}, author = {Derst, C and Dircksen, H and Meusemann, K and Zhou, X and Liu, S and Predel, R}, title = {Evolution of neuropeptides in non-pterygote hexapods.}, journal = {BMC evolutionary biology}, volume = {16}, number = {}, pages = {51}, pmid = {26923142}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; Arthropods/classification/genetics ; *Evolution, Molecular ; Insect Proteins/chemistry/*genetics ; Insecta/classification/*genetics/metabolism ; Molecular Sequence Data ; Neuropeptides/chemistry/*genetics ; Phylogeny ; Transcriptome ; }, abstract = {BACKGROUND: Neuropeptides are key players in information transfer and act as important regulators of development, growth, metabolism, and reproduction within multi-cellular animal organisms (Metazoa). These short protein-like substances show a high degree of structural variability and are recognized as the most diverse group of messenger molecules. We used transcriptome sequences from the 1KITE (1K Insect Transcriptome Evolution) project to search for neuropeptide coding sequences in 24 species from the non-pterygote hexapod lineages Protura (coneheads), Collembola (springtails), Diplura (two-pronged bristletails), Archaeognatha (jumping bristletails), and Zygentoma (silverfish and firebrats), which are often referred to as "basal" hexapods. Phylogenetically, Protura, Collembola, Diplura, and Archaeognatha are currently placed between Remipedia and Pterygota (winged insects); Zygentoma is the sistergroup of Pterygota. The Remipedia are assumed to be among the closest relatives of all hexapods and belong to the crustaceans.

RESULTS: We identified neuropeptide precursor sequences within whole-body transcriptome data from these five hexapod groups and complemented this dataset with homologous sequences from three crustaceans (including Daphnia pulex), three myriapods, and the fruit fly Drosophila melanogaster. Our results indicate that the reported loss of several neuropeptide genes in a number of winged insects, particularly holometabolous insects, is a trend that has occurred within Pterygota. The neuropeptide precursor sequences of the non-pterygote hexapods show numerous amino acid substitutions, gene duplications, variants following alternative splicing, and numbers of paracopies. Nevertheless, most of these features fall within the range of variation known from pterygote insects. However, the capa/pyrokinin genes of non-pterygote hexapods provide an interesting example of rapid evolution, including duplication of a neuropeptide gene encoding different ligands.

CONCLUSIONS: Our findings delineate a basic pattern of neuropeptide sequences that existed before lineage-specific developments occurred during the evolution of pterygote insects.}, } @article {pmid26921294, year = {2016}, author = {Hamaji, T and Mogi, Y and Ferris, PJ and Mori, T and Miyagishima, S and Kabeya, Y and Nishimura, Y and Toyoda, A and Noguchi, H and Fujiyama, A and Olson, BJ and Marriage, TN and Nishii, I and Umen, JG and Nozaki, H}, title = {Sequence of the Gonium pectorale Mating Locus Reveals a Complex and Dynamic History of Changes in Volvocine Algal Mating Haplotypes.}, journal = {G3 (Bethesda, Md.)}, volume = {6}, number = {5}, pages = {1179-1189}, pmid = {26921294}, issn = {2160-1836}, support = {R01 GM078376/GM/NIGMS NIH HHS/United States ; }, mesh = {Chromosome Walking ; Computational Biology ; Evolution, Molecular ; Gene Expression ; Genetic Linkage ; Genome, Plant ; Genomics/methods ; *Haplotypes ; High-Throughput Nucleotide Sequencing ; Phylogeny ; *Quantitative Trait Loci ; Reproduction/*genetics ; Sex Determination Processes/genetics ; Volvox/classification/*genetics ; }, abstract = {Sex-determining regions (SDRs) or mating-type (MT) loci in two sequenced volvocine algal species, Chlamydomonas reinhardtii and Volvox carteri, exhibit major differences in size, structure, gene content, and gametolog differentiation. Understanding the origin of these differences requires investigation of MT loci from related species. Here, we determined the sequences of the minus and plus MT haplotypes of the isogamous 16-celled volvocine alga, Gonium pectorale, which is more closely related to the multicellular V. carteri than to C. reinhardtii Compared to C. reinhardtii MT, G. pectorale MT is moderately larger in size, and has a less complex structure, with only two major syntenic blocs of collinear gametologs. However, the gametolog content of G. pectorale MT has more overlap with that of V. carteri MT than with C. reinhardtii MT, while the allelic divergence between gametologs in G. pectorale is even lower than that in C. reinhardtii Three key sex-related genes are conserved in G. pectorale MT: GpMID and GpMTD1 in MT-, and GpFUS1 in MT+. GpFUS1 protein exhibited specific localization at the plus-gametic mating structure, indicating a conserved function in fertilization. Our results suggest that the G. pectorale-V. carteri common ancestral MT experienced at least one major reformation after the split from C. reinhardtii, and that the V. carteri ancestral MT underwent a subsequent expansion and loss of recombination after the divergence from G. pectorale These data begin to polarize important changes that occurred in volvocine MT loci, and highlight the potential for discontinuous and dynamic evolution in SDRs.}, } @article {pmid26918128, year = {2015}, author = {Bruger, E and Waters, C}, title = {Sharing the sandbox: Evolutionary mechanisms that maintain bacterial cooperation.}, journal = {F1000Research}, volume = {4}, number = {}, pages = {}, pmid = {26918128}, issn = {2046-1402}, support = {R01 GM110444/GM/NIGMS NIH HHS/United States ; }, abstract = {Microbes are now known to participate in an extensive repertoire of cooperative behaviors such as biofilm formation, production of extracellular public-goods, group motility, and higher-ordered multicellular structures. A fundamental question is how these cooperative tasks are maintained in the face of non-cooperating defector cells. Recently, a number of molecular mechanisms including facultative participation, spatial sorting, and policing have been discovered to stabilize cooperation. Often these different mechanisms work in concert to reinforce cooperation. In this review, we describe bacterial cooperation and the current understanding of the molecular mechanisms that maintain it.}, } @article {pmid26917726, year = {2016}, author = {Vilanova, E and Santos, GR and Aquino, RS and Valle-Delgado, JJ and Anselmetti, D and Fernàndez-Busquets, X and Mourão, PA}, title = {Carbohydrate-Carbohydrate Interactions Mediated by Sulfate Esters and Calcium Provide the Cell Adhesion Required for the Emergence of Early Metazoans.}, journal = {The Journal of biological chemistry}, volume = {291}, number = {18}, pages = {9425-9437}, pmid = {26917726}, issn = {1083-351X}, mesh = {Animals ; *Biological Evolution ; Calcium/*chemistry/metabolism ; Microscopy, Atomic Force ; Polysaccharides/*chemistry/metabolism/ultrastructure ; Porifera/*chemistry/metabolism/ultrastructure ; Sulfates/*chemistry/metabolism ; }, abstract = {Early metazoans had to evolve the first cell adhesion mechanism addressed to maintain a distinctive multicellular morphology. As the oldest extant animals, sponges are good candidates for possessing remnants of the molecules responsible for this crucial evolutionary innovation. Cell adhesion in sponges is mediated by the calcium-dependent multivalent self-interactions of sulfated polysaccharides components of extracellular membrane-bound proteoglycans, namely aggregation factors. Here, we used atomic force microscopy to demonstrate that the aggregation factor of the sponge Desmapsamma anchorata has a circular supramolecular structure and that it thus belongs to the spongican family. Its sulfated polysaccharide units, which were characterized via nuclear magnetic resonance analysis, consist preponderantly of a central backbone composed of 3-α-Glc1 units partially sulfated at 2- and 4-positions and branches of Pyr(4,6)α-Gal1→3-α-Fuc2(SO3)1→3-α-Glc4(SO3)1→3-α-Glc→4-linked to the central α-Glc units. Single-molecule force measurements of self-binding forces of this sulfated polysaccharide and their chemically desulfated and carboxyl-reduced derivatives revealed that the sulfate epitopes and extracellular calcium are essential for providing the strength and stability necessary to sustain cell adhesion in sponges. We further discuss these findings within the framework of the role of molecular structures in the early evolution of metazoans.}, } @article {pmid26916163, year = {2016}, author = {Cai, M and Hruby, VJ}, title = {The Melanocortin Receptor System: A Target for Multiple Degenerative Diseases.}, journal = {Current protein & peptide science}, volume = {17}, number = {5}, pages = {488-496}, pmid = {26916163}, issn = {1875-5550}, support = {R01 GM108040/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Drug Design ; Humans ; *Ligands ; Melanocortins/chemistry/genetics/metabolism ; Melanocyte-Stimulating Hormones/chemistry/metabolism ; Models, Molecular ; Molecular Mimicry ; Molecular Structure ; Peptides/chemistry/metabolism ; Protein Conformation ; Receptors, Melanocortin/*chemistry/genetics/*metabolism ; Structure-Activity Relationship ; }, abstract = {The melanocortin receptor system consists of five closely related G-protein coupled receptors (MC1R, MC2R, MC3R, MC4R and MC5R). These receptors are involved in many of the key biological functions for multicellular animals, including human beings. The natural agonist ligands for these receptors are derived by processing of a primordial animal gene product, proopiomelanocortin (POMC). The ligand for the MC2R is ACTH (Adrenal Corticotropic Hormone), a larger processed peptide from POMC. The natural ligands for the other 4 melanocortin receptors are smaller peptides including α-melanocyte stimulating hormone (α-MSH) and related peptides from POMC (β-MSH and γ-MSH). They all contain the sequence His-Phe-Arg-Trp that is conserved throughout evolution. Thus, there has been considerable difficulty in developing highly selective ligands for the MC1R, MC3R, MC4R and MC5R. In this brief review, we discuss the various approaches that have been taken to design agonist and antagonist analogues and derivatives of the POMC peptides that are selective for the MC1R, MC3R, MC4R and MC5R receptors, via peptide, nonpeptide and peptidomimetic derivatives and analogues and their differential interactions with receptors that may help account for these selectivities.}, } @article {pmid26909677, year = {2016}, author = {Strassmann, JE}, title = {Kin Discrimination in Dictyostelium Social Amoebae.}, journal = {The Journal of eukaryotic microbiology}, volume = {63}, number = {3}, pages = {378-383}, doi = {10.1111/jeu.12307}, pmid = {26909677}, issn = {1550-7408}, mesh = {Amoeba/genetics/*physiology ; Animals ; Biological Evolution ; Cell Adhesion/genetics ; Cell Movement ; Dictyostelium/*genetics/*physiology ; Fruiting Bodies, Fungal/genetics ; Protozoan Proteins/genetics ; }, abstract = {Evolved cooperation is stable only when the benefactor is compensated, either directly or through its relatives. Social amoebae cooperate by forming a mobile multicellular body in which, about 20% of participants ultimately die to form a stalk. This benefits the remaining individuals that become hardy spores at the top of the stalk, together making up the fruiting body. In studied species with stalked migration, P. violaceum, D. purpureum, and D. giganteum, sorting based on clone identity occurs in laboratory mixes, maintaining high relatedness within the fruiting bodies. D. discoideum has unstalked migration, where cell fate is not fixed until the slug forms a fruiting body. Laboratory mixes show some degree of both spatial and genotype-based sorting, yet most laboratory fruiting bodies remain chimeric. However, wild fruiting bodies are made up mostly of clonemates. A genetic mechanism for sorting is likely to be cell adhesion genes tgrB1 and tgrC1, which bind to each other. They are highly variable, as expected for a kin discrimination gene. It is a puzzle that these genes do not cause stronger discrimination between mixed wild clones, but laboratory conditions or strong sorting early in the social stage diminished by later slug fusion could be explanations.}, } @article {pmid26907555, year = {2016}, author = {Hermida, M}, title = {Life on Earth is an individual.}, journal = {Theory in biosciences = Theorie in den Biowissenschaften}, volume = {135}, number = {1-2}, pages = {37-44}, pmid = {26907555}, issn = {1611-7530}, mesh = {Biological Evolution ; Biology/*methods ; *Earth, Planet ; Exobiology ; Extinction, Biological ; *Life ; Models, Biological ; *Origin of Life ; Time Factors ; }, abstract = {Life is a self-maintaining process based on metabolism. Something is said to be alive when it exhibits organization and is actively involved in its own continued existence through carrying out metabolic processes. A life is a spatio-temporally restricted event, which continues while the life processes are occurring in a particular chunk of matter (or, arguably, when they are temporally suspended, but can be restarted at any moment), even though there is continuous replacement of parts. Life is organized in discrete packages, particular cells and multicellular organisms with differing degrees of individuality. Biological species, too, have been shown to be individuals, and not classes, as these collections of organisms are spatio-temporally localized, restricted, continuous, and somewhat cohesive entities, with a definite beginning and end. Assuming that all life on Earth has a common origin, all living organisms, cells, and tissues descending from this origin exhibit continuity of the life processes at the cellular level, as well as many of the features that define the individual character of species: spatio-temporal localization and restriction, continuity, historicity, and cohesiveness. Therefore, life on Earth is an ontological individual. Independent origins of life will have produced other such individuals. These provisionally called 'life-individuals' constitute a category of organization of life which has seldom been recognized. The discovery of at least one independent life-individual would go a long way toward the project of the universality of biology.}, } @article {pmid26904394, year = {2016}, author = {Grahame Hardie, D}, title = {Regulation of AMP-activated protein kinase by natural and synthetic activators.}, journal = {Acta pharmaceutica Sinica. B}, volume = {6}, number = {1}, pages = {1-19}, pmid = {26904394}, issn = {2211-3835}, support = {/WT_/Wellcome Trust/United Kingdom ; 097726/WT_/Wellcome Trust/United Kingdom ; }, abstract = {The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells. While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner, during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level, by responding to hormones that act primarily on the hypothalamus. AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP, and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed. Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans, such as type 2 diabetes, cancer and inflammatory disorders, there has been a major drive to develop pharmacological activators of AMPK. Many such activators have been described, and the various mechanisms by which these activate AMPK will be discussed. A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines. While the mechanism by which most of these activate AMPK has not yet been addressed, I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores, and that many of them will turn out to be inhibitors of mitochondrial function.}, } @article {pmid26904071, year = {2016}, author = {Lora, J and Hormaza, JI and Herrero, M}, title = {The Diversity of the Pollen Tube Pathway in Plants: Toward an Increasing Control by the Sporophyte.}, journal = {Frontiers in plant science}, volume = {7}, number = {}, pages = {107}, pmid = {26904071}, issn = {1664-462X}, abstract = {Plants, unlike animals, alternate multicellular diploid, and haploid generations in their life cycle. While this is widespread all along the plant kingdom, the size and autonomy of the diploid sporophyte and the haploid gametophyte generations vary along evolution. Vascular plants show an evolutionary trend toward a reduction of the gametophyte, reflected both in size and lifespan, together with an increasing dependence from the sporophyte. This has resulted in an overlooking of the importance of the gametophytic phase in the evolution of higher plants. This reliance on the sporophyte is most notorious along the pollen tube journey, where the male gametophytes have to travel a long way inside the sporophyte to reach the female gametophyte. Along evolution, there is a change in the scenery of the pollen tube pathway that favors pollen competition and selection. This trend, toward apparently making complicated what could be simple, appears to be related to an increasing control of the sporophyte over the gametophyte with implications for understanding plant evolution.}, } @article {pmid26898901, year = {2016}, author = {Yeo, JH and McAllan, BM and Fraser, ST}, title = {Scanning Electron Microscopy Reveals Two Distinct Classes of Erythroblastic Island Isolated from Adult Mammalian Bone Marrow.}, journal = {Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada}, volume = {22}, number = {2}, pages = {368-378}, doi = {10.1017/S1431927616000155}, pmid = {26898901}, issn = {1435-8115}, mesh = {Animals ; Antigens, CD/analysis ; Blood Group Antigens/analysis ; Bone Marrow/*anatomy & histology ; Bone Marrow Cells/*ultrastructure ; Erythroblasts/*ultrastructure ; Guinea Pigs ; Marsupialia ; Membrane Proteins/analysis ; *Microscopy, Electron, Scanning ; Microscopy, Immunoelectron ; Receptors, Transferrin/analysis ; }, abstract = {Erythroblastic islands are multicellular clusters in which a central macrophage supports the development and maturation of red blood cell (erythroid) progenitors. These clusters play crucial roles in the pathogenesis observed in animal models of hematological disorders. The precise structure and function of erythroblastic islands is poorly understood. Here, we have combined scanning electron microscopy and immuno-gold labeling of surface proteins to develop a better understanding of the ultrastructure of these multicellular clusters. The erythroid-specific surface antigen Ter-119 and the transferrin receptor CD71 exhibited distinct patterns of protein sorting during erythroid cell maturation as detected by immuno-gold labeling. During electron microscopy analysis we observed two distinct classes of erythroblastic islands. The islands varied in size and morphology, and the number and type of erythroid cells interacting with the central macrophage. Assessment of femoral marrow isolated from a cavid rodent species (guinea pig, Cavis porcellus) and a marsupial carnivore species (fat-tailed dunnarts, Sminthopsis crassicaudata) showed that while the morphology of the central macrophage varied, two different types of erythroblastic islands were consistently identifiable. Our findings suggest that these two classes of erythroblastic islands are conserved in mammalian evolution and may play distinct roles in red blood cell production.}, } @article {pmid26897340, year = {2016}, author = {Liongue, C and Taznin, T and Ward, AC}, title = {Signaling via the CytoR/JAK/STAT/SOCS pathway: Emergence during evolution.}, journal = {Molecular immunology}, volume = {71}, number = {}, pages = {166-175}, doi = {10.1016/j.molimm.2016.02.002}, pmid = {26897340}, issn = {1872-9142}, mesh = {Animals ; *Biological Evolution ; Cell Communication/*genetics ; Computational Biology ; Humans ; Janus Kinases/genetics ; Phylogeny ; Receptors, Cytokine/*genetics ; STAT Transcription Factors/genetics ; Signal Transduction/*genetics ; Suppressor of Cytokine Signaling Proteins ; }, abstract = {Cell-cell signaling represents an essential hallmark of multicellular organisms, which necessarily require a means of communicating between different cell populations, particularly immune cells. Cytokine receptor signaling through the Janus kinase/Signal Transducer and Activator of Transcription/Suppressor of Cytokine Signaling (CytoR/JAK/STAT/SOCS) pathway embodies one important paradigm by which this is achieved. This pathway has been extensively studied in vertebrates and protostomes and shown to play fundamental roles in development and function of immune and other cells. However, our understanding of the origins of the individual pathway components and their assembly into a functional pathway has remained limited. This study examined the origins of each component of this pathway through bioinformatics analysis of key extant species. This has revealed step-wise accretion of individual components over a large evolutionary time-frame, but only in bilateria did a series of innovations allow their final coalescence to form a complete pathway. Assembly of the CytoR/JAK/STAT pathway has followed the retrograde model of pathway evolution, whereas addition of the SOCS component has adhered to the patchwork model.}, } @article {pmid26892537, year = {2016}, author = {Yang, EC and Boo, SM and Bhattacharya, D and Saunders, GW and Knoll, AH and Fredericq, S and Graf, L and Yoon, HS}, title = {Divergence time estimates and the evolution of major lineages in the florideophyte red algae.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {21361}, pmid = {26892537}, issn = {2045-2322}, mesh = {Biological Evolution ; *Evolution, Molecular ; Fossils ; *Phylogeny ; Rhodophyta/*classification/*genetics ; }, abstract = {The Florideophyceae is the most abundant and taxonomically diverse class of red algae (Rhodophyta). However, many aspects of the systematics and divergence times of the group remain unresolved. Using a seven-gene concatenated dataset (nuclear EF2, LSU and SSU rRNAs, mitochondrial cox1, and plastid rbcL, psaA and psbA genes), we generated a robust phylogeny of red algae to provide an evolutionary timeline for florideophyte diversification. Our relaxed molecular clock analysis suggests that the Florideophyceae diverged approximately 943 (817-1,049) million years ago (Ma). The major divergences in this class involved the emergence of Hildenbrandiophycidae [ca. 781 (681-879) Ma], Nemaliophycidae [ca. 661 (597-736) Ma], Corallinophycidae [ca. 579 (543-617) Ma], and the split of Ahnfeltiophycidae and Rhodymeniophycidae [ca. 508 (442-580) Ma]. Within these clades, extant diversity reflects largely Phanerozoic diversification. Divergences within Florideophyceae were accompanied by evolutionary changes in the carposporophyte stage, leading to a successful strategy for maximizing spore production from each fertilization event. Our research provides robust estimates for the divergence times of major lineages within the Florideophyceae. This timeline was used to interpret the emergence of key morphological innovations that characterize these multicellular red algae.}, } @article {pmid26886723, year = {2016}, author = {Papaevgeniou, N and Sakellari, M and Jha, S and Tavernarakis, N and Holmberg, CI and Gonos, ES and Chondrogianni, N}, title = {18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures.}, journal = {Antioxidants & redox signaling}, volume = {25}, number = {16}, pages = {855-869}, pmid = {26886723}, issn = {1557-7716}, mesh = {Aging/*metabolism ; Alzheimer Disease/*metabolism/*pathology ; Amyloid beta-Peptides/metabolism ; Animals ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/metabolism ; Cell Death ; Cells, Cultured ; Disease Progression ; Glycyrrhetinic Acid/*analogs & derivatives/metabolism/pharmacology ; Longevity ; Neurons/drug effects/*metabolism ; Oxidation-Reduction ; Phenotype ; Proteasome Endopeptidase Complex/*metabolism ; Protein Aggregation, Pathological/metabolism ; }, abstract = {AIMS: Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Genetically mediated proteasome activation in multicellular organisms has been shown to promote longevity and to exert protein antiaggregation activity. In this study, we investigate whether compound-mediated proteasome activation is feasible in a multicellular organism and we dissect the effects of such approach in aging and Alzheimer's disease (AD) progression.

RESULTS: Feeding of wild-type Caenorhabditis elegans with 18α-glycyrrhetinic acid (18α-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1- and proteasome activation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased Aβ deposits, thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results are also delivered when human and murine cells of nervous origin are subjected to 18α-GA treatment.

INNOVATION: This is the first report of the use of 18α-GA, a diet-derived compound as prolongevity and antiaggregation factor in the context of a multicellular organism.

CONCLUSION: Our results suggest that proteasome activation with downstream positive outcomes on aging and AD, an aggregation-related disease, is feasible in a nongenetic manipulation manner in a multicellular organism. Moreover, they unveil the need for identification of antiaging and antiamyloidogenic compounds among the nutrients found in our normal diet. Antioxid. Redox Signal. 25, 855-869.}, } @article {pmid26873616, year = {2016}, author = {Paz-Y-Miño-C, G and Espinosa, A}, title = {Kin Discrimination in Protists: From Many Cells to Single Cells and Backwards.}, journal = {The Journal of eukaryotic microbiology}, volume = {63}, number = {3}, pages = {367-377}, pmid = {26873616}, issn = {1550-7408}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Biological Evolution ; Eukaryota/*classification/*genetics/physiology ; Genetic Fitness ; Phenotype ; }, abstract = {During four decades (1960-1990s), the conceptualization and experimental design of studies in kin recognition relied on work with multicellular eukaryotes, particularly Unikonta (including invertebrates and vertebrates) and some Bikonta (including plants). This pioneering research had an animal behavior approach. During the 2000s, work on taxa-, clone- and kin-discrimination and recognition in protists produced genetic and molecular evidence that unicellular organisms (e.g. Saccharomyces, Dictyostelium, Polysphondylium, Tetrahymena, Entamoeba and Plasmodium) could distinguish between same (self or clone) and different (diverse clones), as well as among conspecifics of close or distant genetic relatedness. Here, we discuss some of the research on the genetics of kin discrimination/recognition and highlight the scientific progress made by switching emphasis from investigating multicellular to unicellular systems (and backwards). We document how studies with protists are helping us to understand the microscopic, cellular origins and evolution of the mechanisms of kin discrimination/recognition and their significance for the advent of multicellularity. We emphasize that because protists are among the most ancient organisms on Earth, belong to multiple taxonomic groups and occupy all environments, they can be central to reexamining traditional hypotheses in the field of kin recognition, reformulating concepts, and generating new knowledge.}, } @article {pmid26872675, year = {2016}, author = {Moe, GW and Marín-García, J}, title = {Role of cell death in the progression of heart failure.}, journal = {Heart failure reviews}, volume = {21}, number = {2}, pages = {157-167}, pmid = {26872675}, issn = {1573-7322}, mesh = {*Cell Death ; *Disease Progression ; Heart Failure/*physiopathology ; Humans ; Mitochondria, Heart/*metabolism ; Myocytes, Cardiac/*pathology ; Signal Transduction/physiology ; }, abstract = {All multicellular organisms develop during evolution the highly regulated and interconnected pathways of cell death. This complex network contributes to the pathogenesis of various cardiovascular disorders including ischemia/reperfusion injury, myocardial infarction, heart failure, dysrhythmias and atherosclerosis. Chronic cardiac remodeling response and transition to overt HF have been associated with modestly increased apoptosis, although the actual burden of chronic cell loss attributable to apoptosis is not clear. Central mediators of cardiomyocyte survival and death are the mitochondrial organelles. Based on its morphological characteristics, cell death can be classified into three major types: apoptosis, necrosis and autophagy. Recently, a new pathway of regulated necrosis, necroptosis, has also been reported in the failing heart. The mitochondrial (intrinsic) and the death-receptor-mediated (extrinsic) converge at mitochondria inducing release of mitochondrial apoptogens to initiate the caspase cascade and eventually degradation of the doomed cardiomyocyte. Activation of death receptors can initiate not only extrinsic apoptotic pathway, but also necrosis. On the other hand, autophagy, which is characterized by the massive formation of lysosomal-derived vesicles, containing degenerating cytoplasmic contents, is primarily a survival response to nutrient deprivation, and a selective form of autophagy, mitophagy, is also a protective mechanism that allows to eliminate damaged mitochondria and thereby to attenuate mitochondria-mediated apoptosis and necrosis in the myocardium. Further insight into the molecular mechanisms underlying cell death will increase the efficiency and repertoire of therapeutic interventions available in cardiovascular disease.}, } @article {pmid26871911, year = {2016}, author = {Boucher, B and Lee, AY and Hallett, M and Jenna, S}, title = {Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways.}, journal = {PLoS computational biology}, volume = {12}, number = {2}, pages = {e1004738}, pmid = {26871911}, issn = {1553-7358}, mesh = {Animals ; Caenorhabditis elegans/*genetics ; Caenorhabditis elegans Proteins/*genetics/metabolism ; Computational Biology ; Gene Regulatory Networks/*genetics ; Models, Biological ; Protein Interaction Maps/*genetics ; }, abstract = {A genetic interaction (GI) is defined when the mutation of one gene modifies the phenotypic expression associated with the mutation of a second gene. Genome-wide efforts to map GIs in yeast revealed structural and functional properties of a GI network. This provided insights into the mechanisms underlying the robustness of yeast to genetic and environmental insults, and also into the link existing between genotype and phenotype. While a significant conservation of GIs and GI network structure has been reported between distant yeast species, such a conservation is not clear between unicellular and multicellular organisms. Structural and functional characterization of a GI network in these latter organisms is consequently of high interest. In this study, we present an in-depth characterization of ~1.5K GIs in the nematode Caenorhabditis elegans. We identify and characterize six distinct classes of GIs by examining a wide-range of structural and functional properties of genes and network, including co-expression, phenotypical manifestations, relationship with protein-protein interaction dense subnetworks (PDS) and pathways, molecular and biological functions, gene essentiality and pleiotropy. Our study shows that GI classes link genes within pathways and display distinctive properties, specifically towards PDS. It suggests a model in which pathways are composed of PDS-centric and PDS-independent GIs coordinating molecular machines through two specific classes of GIs involving pleiotropic and non-pleiotropic connectors. Our study provides the first in-depth characterization of a GI network within pathways of a multicellular organism. It also suggests a model to understand better how GIs control system robustness and evolution.}, } @article {pmid26869214, year = {2016}, author = {Tudge, SJ and Watson, RA and Brede, M}, title = {Game theoretic treatments for the differentiation of functional roles in the transition to multicellularity.}, journal = {Journal of theoretical biology}, volume = {395}, number = {}, pages = {161-173}, doi = {10.1016/j.jtbi.2016.01.041}, pmid = {26869214}, issn = {1095-8541}, mesh = {*Biological Evolution ; *Game Theory ; *Models, Biological ; }, abstract = {Multicellular organisms are characterised by role specialisation, brought about by the epigenetic differentiation of their constituent parts. Conventional game theoretic studies of cooperation do not account for this division of labour, nor do they allow for the possibility of the plastic expression of phenotype. We address these issues by extending the notion of cooperative dilemmas to account for such interaction in which heterogeneous roles are advantageous and present an extended dynamical model of selection that allows for the possibility of conditional expression of phenotype. We use these models to investigate systematically when selection will favour an adaptive diversification of roles. We argue that such extensions to models and concepts are necessary to understand the origins of multicellularity and development.}, } @article {pmid26868766, year = {2016}, author = {Willemsen, A and Zwart, MP and Tromas, N and Majer, E and Daròs, JA and Elena, SF}, title = {Multiple Barriers to the Evolution of Alternative Gene Orders in a Positive-Strand RNA Virus.}, journal = {Genetics}, volume = {202}, number = {4}, pages = {1503-1521}, pmid = {26868766}, issn = {1943-2631}, mesh = {Biological Evolution ; *Evolution, Molecular ; Gene Deletion ; Gene Duplication ; *Gene Order ; Genetic Fitness ; *Genetic Variation ; Genome, Viral ; High-Throughput Nucleotide Sequencing ; Phylogeny ; Plant Viruses/genetics ; Polymorphism, Single Nucleotide ; RNA Viruses/classification/*genetics ; *RNA, Viral ; }, abstract = {The order in which genes are organized within a genome is generally not conserved between distantly related species. However, within virus orders and families, strong conservation of gene order is observed. The factors that constrain or promote gene-order diversity are largely unknown, although the regulation of gene expression is one important constraint for viruses. Here we investigate why gene order is conserved for a positive-strand RNA virus encoding a single polyprotein in the context of its authentic multicellular host. Initially, we identified the most plausible trajectory by which alternative gene orders could evolve. Subsequently, we studied the accessibility of key steps along this evolutionary trajectory by constructing two virus intermediates: (1) duplication of a gene followed by (2) loss of the ancestral gene. We identified five barriers to the evolution of alternative gene orders. First, the number of viable positions for reordering is limited. Second, the within-host fitness of viruses with gene duplications is low compared to the wild-type virus. Third, after duplication, the ancestral gene copy is always maintained and never the duplicated one. Fourth, viruses with an alternative gene order have even lower fitness than viruses with gene duplications. Fifth, after more than half a year of evolution in isolation, viruses with an alternative gene order are still vastly inferior to the wild-type virus. Our results show that all steps along plausible evolutionary trajectories to alternative gene orders are highly unlikely. Hence, the inaccessibility of these trajectories probably contributes to the conservation of gene order in present-day viruses.}, } @article {pmid26866800, year = {2016}, author = {Koga, H and Fujitani, H and Morino, Y and Miyamoto, N and Tsuchimoto, J and Shibata, TF and Nozawa, M and Shigenobu, S and Ogura, A and Tachibana, K and Kiyomoto, M and Amemiya, S and Wada, H}, title = {Experimental Approach Reveals the Role of alx1 in the Evolution of the Echinoderm Larval Skeleton.}, journal = {PloS one}, volume = {11}, number = {2}, pages = {e0149067}, pmid = {26866800}, issn = {1932-6203}, mesh = {Animals ; Biological Evolution ; Echinodermata/genetics/*physiology ; Gene Expression Profiling ; *Gene Expression Regulation ; Homeodomain Proteins/*genetics/*physiology ; Immunohistochemistry ; In Situ Hybridization ; Larva/genetics/physiology ; Phenotype ; Phylogeny ; Sea Cucumbers/genetics/physiology ; Sequence Analysis, RNA ; Starfish/*genetics/*physiology ; Strongylocentrotus purpuratus/genetics/physiology ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {Over the course of evolution, the acquisition of novel structures has ultimately led to wide variation in morphology among extant multicellular organisms. Thus, the origins of genetic systems for new morphological structures are a subject of great interest in evolutionary biology. The larval skeleton is a novel structure acquired in some echinoderm lineages via the activation of the adult skeletogenic machinery. Previously, VEGF signaling was suggested to have played an important role in the acquisition of the larval skeleton. In the present study, we compared expression patterns of Alx genes among echinoderm classes to further explore the factors involved in the acquisition of a larval skeleton. We found that the alx1 gene, originally described as crucial for sea urchin skeletogenesis, may have also played an essential role in the evolution of the larval skeleton. Unlike those echinoderms that have a larval skeleton, we found that alx1 of starfish was barely expressed in early larvae that have no skeleton. When alx1 overexpression was induced via injection of alx1 mRNA into starfish eggs, the expression patterns of certain genes, including those possibly involved in skeletogenesis, were altered. This suggested that a portion of the skeletogenic program was induced solely by alx1. However, we observed no obvious external phenotype or skeleton. We concluded that alx1 was necessary but not sufficient for the acquisition of the larval skeleton, which, in fact, requires several genetic events. Based on these results, we discuss how the larval expression of alx1 contributed to the acquisition of the larval skeleton in the putative ancestral lineage of echinoderms.}, } @article {pmid26864038, year = {2016}, author = {Singer, MA}, title = {The Origins of Aging: Evidence that Aging is an Adaptive Phenotype.}, journal = {Current aging science}, volume = {9}, number = {2}, pages = {95-115}, doi = {10.2174/1874609809666160211124947}, pmid = {26864038}, issn = {1874-6128}, mesh = {*Adaptation, Physiological ; *Aging ; Animals ; Biological Evolution ; Cellular Senescence ; Ecosystem ; Humans ; Models, Biological ; }, abstract = {BACKGROUND: Aging can be defined as the time-related decline in biological functions which ultimately results in organismal death. Beyond the stage of reproductive maturity as fertility declines, cell and tissue functions come under reduced selection pressure since organismal survival is considered no longer an evolutionary priority. Repair mechanisms become less robust and the resulting stochastic accumulation of tissue and genomic damage is believed to underlie the aging process. The objective of this review is to challenge this construct and to present evidence that aging represents a species-specific adaptive developmental program.

METHODS: Through a review of published data, the cellular aging programs of both single cell and multicellular organisms are described. Since all organisms live in communities (ecosystems) of diverse species, the role of multi-level selection is discussed within this context and a proposal is advanced that aging represents an adaptive phenotype.

RESULTS: Single cell organisms evolved an aging phenotype in which the primary feature was replicative arrest prior to cell death. The evolution of multicellularity represented the emergence of a new level of biological organization. Multicellularity required cell-cell cooperation as well as a division of labor. In simple multicellular organisms aging was rooted in an age-related decline in stem cell function (renewal and differentiation). In complex multicellular organisms cellular aging/ death programs (senescence, autophagy, apoptosis) were used as a form of cell "altruistic" suicide carried out for the benefit of the whole organism (morphogenesis, tissue repair and maintenance). Organisms do not live in isolation. Species occupy ecological niches and communities of diverse species comprise an ecosystem. Ecosystems are highly regulated and structured biological organizations. The effective functioning and productivity of an ecosystem is determined by its biological diversity and relative species densities. Multilevel selection acts to balance optimal functioning of both the whole ecosystem and its compositional species/organisms.

CONCLUSIONS: Organismal aging and death programs are adaptive; these programs provide a mechanism for regulating species population densities within the constraints imposed by the ecosystem organization. A unique feature of humans has been the development of a second inheritance system, culture. Through cultural practices, humans have expanded our ecological niche to be global in size. Our technology enriched urban ecosystem is very different from natural ecosystems. Our future evolution, including aging and lifespan, will be determined by our unique urban ecosystem through geneculture co-evolution.}, } @article {pmid26863993, year = {2016}, author = {Lavrov, AI and Kosevich, IA}, title = {Sponge cell reaggregation: Cellular structure and morphogenetic potencies of multicellular aggregates.}, journal = {Journal of experimental zoology. Part A, Ecological genetics and physiology}, volume = {325}, number = {2}, pages = {158-177}, doi = {10.1002/jez.2006}, pmid = {26863993}, issn = {1932-5231}, mesh = {Animals ; Cell Aggregation ; Cell Movement ; Cellular Structures/cytology ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; *Morphogenesis ; Porifera/*cytology/*growth & development/ultrastructure ; Species Specificity ; }, abstract = {Sponges (phylum Porifera) are one of the most ancient extant multicellular animals and can provide valuable insights into origin and early evolution of Metazoa. High plasticity of cell differentiations and anatomical structure is characteristic feature of sponges. Present study deals with sponge cell reaggregation after dissociation as the most outstanding case of sponge plasticity. Dynamic of cell reaggregation and structure of multicellular aggregates of three demosponge species (Halichondria panicea (Pallas, 1766), Haliclona aquaeductus (Sсhmidt, 1862), and Halisarca dujardinii Johnston, 1842) were studied. Sponge tissue dissociation was performed mechanically. Resulting cell suspensions were cultured at 8-10°C for at least 5 days. Structure of multicellular aggregates was studied by light, transmission and scanning electron microscopy. Studied species share common stages of cell reaggregation-primary multicellular aggregates, early-stage primmorphs and primmorphs, but the rate of reaggregation varies considerably among species. Only cells of H. dujardinii are able to reconstruct functional and viable sponge after primmorphs formation. Sponge reconstruction in this species occurs due to active cell locomotion. Development of H. aquaeductus and H. panicea cells ceases at the stages of early primmorphs and primmorphs, respectively. Development of aggregates of these species is most likely arrested due to immobility of the majority of cells inside them. However, the inability of certain sponge species to reconstruct functional and viable individuals during cell reaggregation may be not a permanent species-specific characteristic, but depends on various factors, including the stage of the life cycle and experimental conditions.}, } @article {pmid26859352, year = {2016}, author = {Plavskin, Y and Nagashima, A and Perroud, PF and Hasebe, M and Quatrano, RS and Atwal, GS and Timmermans, MC}, title = {Ancient trans-Acting siRNAs Confer Robustness and Sensitivity onto the Auxin Response.}, journal = {Developmental cell}, volume = {36}, number = {3}, pages = {276-289}, pmid = {26859352}, issn = {1878-1551}, support = {T32 GM065094/GM/NIGMS NIH HHS/United States ; 5T32GM065094/GM/NIGMS NIH HHS/United States ; }, mesh = {Gene Expression Regulation, Plant/*genetics ; Gene Regulatory Networks/*genetics ; Indoleacetic Acids/*metabolism ; MicroRNAs/genetics ; Plant Proteins/genetics ; RNA, Plant/*genetics ; RNA, Small Interfering/*genetics ; Signal Transduction/physiology ; }, abstract = {Novel developmental programs often evolve via cooption of existing genetic networks. To understand this process, we explored cooption of the TAS3 tasiRNA pathway in the moss Physcomitrella patens. We find an ancestral function for this repeatedly redeployed pathway in the spatial regulation of a conserved set of Auxin Response Factors. In moss, this results in stochastic patterning of the filamentous protonemal tissue. Through modeling and experimentation, we demonstrate that tasiRNA regulation confers sensitivity and robustness onto the auxin response. Increased auxin sensitivity parallels increased developmental sensitivity to nitrogen, a key environmental signal. We propose that the properties lent to the auxin response network, along with the ability to stochastically modulate development in response to environmental cues, have contributed to repeated cooption of the tasiRNA-ARF module during evolution. The signaling properties of a genetic network, and not just its developmental output, are thus critical to understanding evolution of multicellular forms.}, } @article {pmid26852925, year = {2016}, author = {Kim, W and Levy, SB and Foster, KR}, title = {Rapid radiation in bacteria leads to a division of labour.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {10508}, pmid = {26852925}, issn = {2041-1723}, support = {242670/ERC_/European Research Council/International ; P50 GM068763/GM/NIGMS NIH HHS/United States ; 5P50 GM 068763/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria ; Bacterial Proteins/genetics ; *Biological Evolution ; Cyclic GMP/analogs & derivatives/biosynthesis ; Frameshift Mutation ; Microbial Interactions/*physiology ; Pseudomonas fluorescens/genetics/*physiology ; }, abstract = {The division of labour is a central feature of the most sophisticated biological systems, including genomes, multicellular organisms and societies, which took millions of years to evolve. Here we show that a well-organized and robust division of labour can evolve in a matter of days. Mutants emerge within bacterial colonies and work with the parent strain to gain new territory. The two strains self-organize in space: one provides a wetting polymer at the colony edge, whereas the other sits behind and pushes them both along. The emergence of the interaction is repeatable, bidirectional and only requires a single mutation to alter production of the intracellular messenger, cyclic-di-GMP. Our work demonstrates the power of the division of labour to rapidly solve biological problems without the need for long-term evolution or derived sociality. We predict that the division of labour will evolve frequently in microbial populations, where rapid genetic diversification is common.}, } @article {pmid26836977, year = {2016}, author = {Trapani, MR and Parisi, MG and Parrinello, D and Sanfratello, MA and Benenati, G and Palla, F and Cammarata, M}, title = {Specific inflammatory response of Anemonia sulcata (Cnidaria) after bacterial injection causes tissue reaction and enzymatic activity alteration.}, journal = {Journal of invertebrate pathology}, volume = {135}, number = {}, pages = {15-21}, doi = {10.1016/j.jip.2016.01.010}, pmid = {26836977}, issn = {1096-0805}, mesh = {Alkaline Phosphatase/metabolism ; Animals ; Densitometry ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli/*physiology ; Esterases/metabolism ; Fibrinogen/metabolism ; Fibrinolysis ; Gelatin/metabolism ; Host-Pathogen Interactions ; Inflammation ; Peptide Hydrolases/metabolism ; Phosphoric Monoester Hydrolases/metabolism ; Sea Anemones/enzymology/*microbiology/physiology ; Vibrio alginolyticus/*physiology ; }, abstract = {The evolution of multicellular organisms was marked by adaptations to protect against pathogens. The mechanisms for discriminating the ''self'' from ''non-self" have evolved into a long history of cellular and molecular strategies, from damage repair to the co-evolution of host-pathogen interactions. We investigated the inflammatory response in Anemonia sulcata (Cnidaria: Anthozoa) following injection of substances that varied in type and dimension, and observed clear, strong and specific reactions, especially after injection of Escherichia coli and Vibrio alginolyticus. Moreover, we analyzed enzymatic activity of protease, phosphatase and esterase, showing how the injection of different bacterial strains alters the expression of these enzymes and suggesting a correlation between the appearance of the inflammatory reaction and the modification of enzymatic activities. Our study shows for the first time, a specific reaction and enzymatic responses following injection of bacteria in a cnidarian.}, } @article {pmid26833268, year = {2016}, author = {Ripamonti, U}, title = {Redefining the induction of periodontal tissue regeneration in primates by the osteogenic proteins of the transforming growth factor-β supergene family.}, journal = {Journal of periodontal research}, volume = {51}, number = {6}, pages = {699-715}, doi = {10.1111/jre.12356}, pmid = {26833268}, issn = {1600-0765}, mesh = {Animals ; Cementogenesis/drug effects ; Collagen/pharmacology ; Drug Combinations ; Laminin/pharmacology ; Papio ursinus ; Periodontium/drug effects/*physiology ; Primates ; Proteoglycans/pharmacology ; Regeneration/*drug effects/physiology ; Transforming Growth Factor beta/genetics/*pharmacology ; }, abstract = {The molecular bases of periodontal tissue induction and regeneration are the osteogenic proteins of the transforming growth factor-β (TGF-β) supergene family. These morphogens act as soluble mediators for the induction of tissues morphogenesis sculpting the multicellular mineralized structures of the periodontal tissues with functionally oriented ligament fibers into newly formed cementum. Human TGF-β3 (hTGF-β3) in growth factor-reduced Matrigel[®] matrix induces cementogenesis when implanted in class II mandibular furcation defects surgically prepared in the non-human primate Chacma baboon, Papio ursinus. The newly formed periodontal ligament space is characterized by running fibers tightly attached to the cementoid surface penetrating as mineralized constructs within the newly formed cementum assembling and initiating within the mineralized dentine. Angiogenesis heralds the newly formed periodontal ligament space, and newly sprouting capillaries are lined by cellular elements with condensed chromatin interpreted as angioblasts responsible for the rapid and sustained induction of angiogenesis. The inductive activity of hTGF-β3 in Matrigel[®] matrix is enhanced by the addition of autogenous morcellated fragments of the rectus abdominis muscle potentially providing myoblastic, pericytic/perivascular stem cells for continuous tissue induction and morphogenesis. The striated rectus abdominis muscle is endowed with stem cell niches in para/perivascular location, which can be dominant, thus imposing stem cell features or stemness to the surrounding cells. This capacity to impose stemness is morphologically shown by greater alveolar bone induction and cementogenesis when hTGF-β3 in Matrigel[®] matrix is combined with morcellated fragments of autogenous rectus abdominis muscle. The induction of periodontal tissue morphogenesis develops as a mosaic structure in which the osteogenic proteins of the TGF-β supergene family singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis. In primates, the presence of several homologous yet molecularly different isoforms with osteogenic activity highlights the biological significance of this apparent redundancy and indicates multiple interactions during embryonic development and bone regeneration in postnatal life. Molecular redundancy with associated different biological functionalities in primate tissues may simply represent the fine-tuning of speciation-related molecular evolution in anthropoid apes at the early Pliocene boundary, which resulted in finer tuning of the bone induction cascade.}, } @article {pmid26831906, year = {2016}, author = {Jindrich, K and Degnan, BM}, title = {The diversification of the basic leucine zipper family in eukaryotes correlates with the evolution of multicellularity.}, journal = {BMC evolutionary biology}, volume = {16}, number = {}, pages = {28}, pmid = {26831906}, issn = {1471-2148}, mesh = {Animals ; Chromosome Mapping ; Eukaryota/classification/*genetics ; *Evolution, Molecular ; Fungi/genetics ; Leucine Zippers ; Phylogeny ; Plants/genetics ; Protein Structure, Tertiary ; Transcription Factors/chemistry/*genetics ; }, abstract = {BACKGROUND: Multicellularity evolved multiple times in eukaryotes. In all cases, this required an elaboration of the regulatory mechanisms controlling gene expression. Amongst the conserved eukaryotic transcription factor families, the basic leucine zipper (bZIP) superfamily is one of the most ancient and best characterised. This gene family plays a diversity of roles in the specification, differentiation and maintenance of cell types in plants and animals. bZIPs are also involved in stress responses and the regulation of cell proliferation in fungi, amoebozoans and heterokonts.

RESULTS: Using 49 sequenced genomes from across the Eukaryota, we demonstrate that the bZIP superfamily has evolved from a single ancestral eukaryotic gene and undergone multiple independent expansions. bZIP family diversification is largely restricted to multicellular lineages, consistent with bZIPs contributing to the complex regulatory networks underlying differential and cell type-specific gene expression in these lineages. Analyses focused on the Metazoa suggest an elaborate bZIP network was in place in the most recent shared ancestor of all extant animals that was comprised of 11 of the 12 previously recognized families present in modern taxa. In addition this analysis identifies three bZIP families that appear to have been lost in mammals. Thus the ancestral metazoan and eumetazoan bZIP repertoire consists of 12 and 16 bZIPs, respectively. These diversified from 7 founder genes present in the holozoan ancestor.

CONCLUSIONS: Our results reveal the ancestral opisthokont, holozoan and metazoan bZIP repertoire and provide insights into the progressive expansion and divergence of bZIPs in the five main eukaryotic kingdoms, suggesting that the early diversification of bZIPs in multiple eukaryotic lineages was a prerequisite for the evolution of complex multicellular organisms.}, } @article {pmid26822195, year = {2016}, author = {Herron, MD}, title = {Origins of multicellular complexity: Volvox and the volvocine algae.}, journal = {Molecular ecology}, volume = {25}, number = {6}, pages = {1213-1223}, pmid = {26822195}, issn = {1365-294X}, support = {NNA17BB05A//Intramural NASA/United States ; }, mesh = {*Biological Evolution ; Cell Differentiation ; Cell Movement ; Chlamydomonas/genetics/physiology ; Congresses as Topic ; Phylogeny ; Volvox/*genetics/*physiology ; }, abstract = {The collection of evolutionary transformations known as the 'major transitions' or 'transitions in individuality' resulted in changes in the units of evolution and in the hierarchical structure of cellular life. Volvox and related algae have become an important model system for the major transition from unicellular to multicellular life, which touches on several fundamental questions in evolutionary biology. The Third International Volvox Conference was held at the University of Cambridge in August 2015 to discuss recent advances in the biology and evolution of this group of algae. Here, I highlight the benefits of integrating phylogenetic comparative methods and experimental evolution with detailed studies of developmental genetics in a model system with substantial genetic and genomic resources. I summarize recent research on Volvox and its relatives and comment on its implications for the genomic changes underlying major evolutionary transitions, evolution and development of complex traits, evolution of sex and sexes, evolution of cellular differentiation and the biophysics of motility. Finally, I outline challenges and suggest future directions for research into the biology and evolution of the volvocine algae.}, } @article {pmid26803291, year = {2016}, author = {Cristea, A and Neagu, A}, title = {Shape changes of bioprinted tissue constructs simulated by the Lattice Boltzmann method.}, journal = {Computers in biology and medicine}, volume = {70}, number = {}, pages = {80-87}, doi = {10.1016/j.compbiomed.2015.12.020}, pmid = {26803291}, issn = {1879-0534}, mesh = {Imaging, Three-Dimensional/*methods ; *Models, Theoretical ; *Tissue Engineering ; }, abstract = {Tissue engineers seek to build living tissue constructs for replacing or repairing damaged tissues. Computational methods foster tissue engineering by pointing out dominant mechanisms involved in shaping multicellular systems. Here we apply the Lattice Boltzmann (LB) method to study the fusion of multicellular constructs. This process is of interest in bioprinting, in which multicellular spheroids or cylinders are embedded in a supportive hydrogel by a computer-controlled device. We simulated post-printing rearrangements of cells, aiming to predict the shape and stability of certain printed structures. To this end, we developed a two-dimensional LB model of a multicellular system in a hydrogel. Our parallel computing code was implemented using the Portable Extensible Toolkit for Scientific Computation (PETSc). To validate the LB model, we simulated the fusion of multicellular cylinders in a contiguous, hexagonal arrangement. Our two-dimensional LB simulation describes the evolution of the transversal cross section of the construct built from three-dimensional multicellular cylinders whose length is much larger than their diameter. Fusion eventually gave rise to a tubular construct, in qualitative agreement with bioprinting experiments. Then we simulated the time course of a defect in a bioprinted tube. To address practical problems encountered in tissue engineering, we also simulated the evolution of a planar construct, as well as of a bulky, perfusable construct made of multicellular cylinders. The agreement with experiments indicates that our LB model captures certain essential features of morphogenesis, and, therefore, it may be used to test new working hypotheses faster and cheaper than in the laboratory.}, } @article {pmid26793205, year = {2015}, author = {Sharma, M and Pandey, GK}, title = {Expansion and Function of Repeat Domain Proteins During Stress and Development in Plants.}, journal = {Frontiers in plant science}, volume = {6}, number = {}, pages = {1218}, pmid = {26793205}, issn = {1664-462X}, abstract = {The recurrent repeats having conserved stretches of amino acids exists across all domains of life. Subsequent repetition of single sequence motif and the number and length of the minimal repeating motifs are essential characteristics innate to these proteins. The proteins with tandem peptide repeats are essential for providing surface to mediate protein-protein interactions for fundamental biological functions. Plants are enriched in tandem repeat containing proteins typically distributed into various families. This has been assumed that the occurrence of multigene repeats families in plants enable them to cope up with adverse environmental conditions and allow them to rapidly acclimatize to these conditions. The evolution, structure, and function of repeat proteins have been studied in all kingdoms of life. The presence of repeat proteins is particularly profuse in multicellular organisms in comparison to prokaryotes. The precipitous expansion of repeat proteins in plants is presumed to be through internal tandem duplications. Several repeat protein gene families have been identified in plants. Such as Armadillo (ARM), Ankyrin (ANK), HEAT, Kelch-like repeats, Tetratricopeptide (TPR), Leucine rich repeats (LRR), WD40, and Pentatricopeptide repeats (PPR). The structure and functions of these repeat proteins have been extensively studied in plants suggesting a critical role of these repeating peptides in plant cell physiology, stress and development. In this review, we illustrate the structural, functional, and evolutionary prospects of prolific repeat proteins in plants.}, } @article {pmid26790885, year = {2016}, author = {Anderson, DP and Whitney, DS and Hanson-Smith, V and Woznica, A and Campodonico-Burnett, W and Volkman, BF and King, N and Thornton, JW and Prehoda, KE}, title = {Correction: Evolution of an ancient protein function involved in organized multicellularity in animals.}, journal = {eLife}, volume = {5}, number = {}, pages = {e14311}, doi = {10.7554/eLife.14311}, pmid = {26790885}, issn = {2050-084X}, } @article {pmid26787762, year = {2016}, author = {Dey, A and Vassallo, CN and Conklin, AC and Pathak, DT and Troselj, V and Wall, D}, title = {Sibling Rivalry in Myxococcus xanthus Is Mediated by Kin Recognition and a Polyploid Prophage.}, journal = {Journal of bacteriology}, volume = {198}, number = {6}, pages = {994-1004}, pmid = {26787762}, issn = {1098-5530}, support = {R01 GM101449/GM/NIGMS NIH HHS/United States ; GM101449/GM/NIGMS NIH HHS/United States ; }, mesh = {*Antibiosis ; Bacterial Toxins/metabolism ; Cell Membrane/metabolism ; *Gene Dosage ; Myxococcus xanthus/genetics/*physiology/*virology ; Prophages/*genetics ; Protein Transport ; Receptors, Cell Surface/*metabolism ; Sequence Deletion ; }, abstract = {UNLABELLED: Myxobacteria form complex social communities that elicit multicellular behaviors. One such behavior is kin recognition, in which cells identify siblings via their polymorphic TraA cell surface receptor, to transiently fuse outer membranes and exchange their contents. In addition, outer membrane exchange (OME) regulates behaviors, such as inhibition of wild-type Myxococcus xanthus (DK1622) from swarming. Here we monitored the fate of motile cells and surprisingly found they were killed by nonmotile siblings. The kill phenotype required OME (i.e., was TraA dependent). The genetic basis of killing was traced to ancestral strains used to construct DK1622. Specifically, the kill phenotype mapped to a large "polyploid prophage," Mx alpha. Sensitive strains contained a 200-kb deletion that removed two of three Mx alpha units. To explain these results, we suggest that Mx alpha expresses a toxin-antitoxin cassette that uses the OME machinery of M. xanthus to transfer a toxin that makes the population "addicted" to Mx alpha. Thus, siblings that lost Mx alpha units (no immunity) are killed by cells that harbor the element. To test this, an Mx alpha-harboring laboratory strain was engineered (by traA allele swap) to recognize a closely related species, Myxococcus fulvus. As a result, M. fulvus, which lacks Mx alpha, was killed. These TraA-mediated antagonisms provide an explanation for how kin recognition specificity might have evolved in myxobacteria. That is, recognition specificity is determined by polymorphisms in traA, which we hypothesize were selected for because OME with non-kin leads to lethal outcomes.

IMPORTANCE: The transition from single cell to multicellular life is considered a major evolutionary event. Myxobacteria have successfully made this transition. For example, in response to starvation, individual cells aggregate into multicellular fruiting bodies wherein cells differentiate into spores. To build fruits, cells need to recognize their siblings, and in part, this is mediated by the TraA cell surface receptor. Surprisingly, we report that TraA recognition can also involve sibling killing. We show that killing originates from a prophage-like element that has apparently hijacked the TraA system to deliver a toxin to kin. We hypothesize that this killing system has imposed selective pressures on kin recognition, which in turn has resulted in TraA polymorphisms and hence many different recognition groups.}, } @article {pmid26787743, year = {2016}, author = {Kumar, D and Blaby-Haas, CE and Merchant, SS and Mains, RE and King, SM and Eipper, BA}, title = {Early eukaryotic origins for cilia-associated bioactive peptide-amidating activity.}, journal = {Journal of cell science}, volume = {129}, number = {5}, pages = {943-956}, pmid = {26787743}, issn = {1477-9137}, support = {GM051293/GM/NIGMS NIH HHS/United States ; R37 GM042143/GM/NIGMS NIH HHS/United States ; R56 DK032949/DK/NIDDK NIH HHS/United States ; DK032949/DK/NIDDK NIH HHS/United States ; GM100753/GM/NIGMS NIH HHS/United States ; R37 DK032949/DK/NIDDK NIH HHS/United States ; R01 DK032949/DK/NIDDK NIH HHS/United States ; R01 GM042143/GM/NIGMS NIH HHS/United States ; GM042143/GM/NIGMS NIH HHS/United States ; R01 GM051293/GM/NIGMS NIH HHS/United States ; F32 GM100753/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Chlamydomonas reinhardtii/*enzymology/ultrastructure ; Cilia/*enzymology ; Evolution, Molecular ; HEK293 Cells ; Humans ; Mice ; NIH 3T3 Cells ; Nitrogenous Group Transferases/*genetics/metabolism ; Plant Proteins/*genetics/metabolism ; Protein Processing, Post-Translational ; Protein Transport ; }, abstract = {Ciliary axonemes and basal bodies were present in the last eukaryotic common ancestor and play crucial roles in sensing and responding to environmental cues. Peptidergic signaling, generally considered a metazoan innovation, is essential for organismal development and homeostasis. Peptidylglycine α-amidating monooxygenase (PAM) is crucial for the last step of bioactive peptide biosynthesis. However, identification of a complete PAM-like gene in green algal genomes suggests ancient evolutionary roots for bioactive peptide signaling. We demonstrate that the Chlamydomonas reinhardtii PAM gene encodes an active peptide-amidating enzyme (CrPAM) that shares key structural and functional features with the mammalian enzyme, indicating that components of the peptide biosynthetic pathway predate multicellularity. In addition to its secretory pathway localization, CrPAM localizes to cilia and tightly associates with the axonemal superstructure, revealing a new axonemal enzyme activity. This localization pattern is conserved in mammals, with PAM present in both motile and immotile sensory cilia. The conserved ciliary localization of PAM adds to the known signaling capabilities of the eukaryotic cilium and provides a potential mechanistic link between peptidergic signaling and endocrine abnormalities commonly observed in ciliopathies.}, } @article {pmid26784245, year = {2016}, author = {Murata, A and Hayashi, S}, title = {Notch-Mediated Cell Adhesion.}, journal = {Biology}, volume = {5}, number = {1}, pages = {}, pmid = {26784245}, issn = {2079-7737}, abstract = {Notch family members are generally recognized as signaling molecules that control various cellular responses in metazoan organisms. Early fly studies and our mammalian studies demonstrated that Notch family members are also cell adhesion molecules; however, information on the physiological roles of this function and its origin is limited. In this review, we discuss the potential present and ancestral roles of Notch-mediated cell adhesion in order to explore its origin and the initial roles of Notch family members dating back to metazoan evolution. We hypothesize that Notch family members may have initially emerged as cell adhesion molecules in order to mediate multicellularity in the last common ancestor of metazoan organisms.}, } @article {pmid26777788, year = {2016}, author = {Gillings, MR and Hilbert, M and Kemp, DJ}, title = {Information in the Biosphere: Biological and Digital Worlds.}, journal = {Trends in ecology & evolution}, volume = {31}, number = {3}, pages = {180-189}, doi = {10.1016/j.tree.2015.12.013}, pmid = {26777788}, issn = {1872-8383}, mesh = {Biological Evolution ; Humans ; *Information Dissemination ; *Online Systems ; Selection, Genetic ; }, abstract = {Evolution has transformed life through key innovations in information storage and replication, including RNA, DNA, multicellularity, and culture and language. We argue that the carbon-based biosphere has generated a cognitive system (humans) capable of creating technology that will result in a comparable evolutionary transition. Digital information has reached a similar magnitude to information in the biosphere. It increases exponentially, exhibits high-fidelity replication, evolves through differential fitness, is expressed through artificial intelligence (AI), and has facility for virtually limitless recombination. Like previous evolutionary transitions, the potential symbiosis between biological and digital information will reach a critical point where these codes could compete via natural selection. Alternatively, this fusion could create a higher-level superorganism employing a low-conflict division of labor in performing informational tasks.}, } @article {pmid26777340, year = {2016}, author = {Neill, D}, title = {Individual Cell Longevity, 'Life's Timekeeper', and Metazoan Evolution.}, journal = {Current aging science}, volume = {9}, number = {2}, pages = {87-98}, doi = {10.2174/1874609809666160114092340}, pmid = {26777340}, issn = {1874-6128}, mesh = {Animals ; *Biological Evolution ; Cell Survival ; *Cellular Senescence ; Humans ; Signal Transduction ; }, abstract = {It is proposed that a primary and fundamental aspect of metazoan evolution is an ability to control and extend the longevity of individual cells. This was achieved through an intracellular oscillator, dubbed 'Life's Timekeeper', which evolved in the hypothetical ancestor of all metazoans. Slower oscillatory frequencies directed metazoan evolution towards extended longevity of individual cells, enabling generation of many specialised types of terminally differentiated cells. As the longevity of these cells was still relatively short in more primitive metazoans, stem cells, capable of differentiating into all specialised cell types, were retained in order to replace senescent cells. With increasing cell longevity, continual replacement of all senescent cells was no longer necessary. Cells such as neurons could be sustained throughout life, enabling the evolution of brains, hence, complex behaviour and intelligence. In multicellular metazoans the oscillator remains synchronised across all cells. It coordinates the timing of all cell-cell signalling systems, hence controls the timing of development and aging/senescence. In advanced metazoans, where senescent cells are not continually replaced, it controls lifespan. With regards to morphological evolution the oscillator, through alterations to developmental timing, controls change in size and shape. With regards to life history theory it functions as the key variable mediating the correlation between life history traits. This theory is compatible with a prominent role for environmental selection but, as it implicates some degree of internal mediation and direction, it is not entirely compatible with the 'modern synthesis' view of natural selection.}, } @article {pmid26775799, year = {2016}, author = {Mukherjee, S and Karmakar, S and Babu, SP}, title = {TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review.}, journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases}, volume = {20}, number = {2}, pages = {193-204}, pmid = {26775799}, issn = {1678-4391}, mesh = {Communicable Diseases/*immunology ; Host-Parasite Interactions/*immunology ; Host-Pathogen Interactions/*immunology ; Humans ; Immunity, Humoral/*immunology ; Toll-Like Receptor 2/*immunology ; Toll-Like Receptor 4/*immunology ; }, abstract = {During the course of evolution, multicellular organisms have been orchestrated with an efficient and versatile immune system to counteract diverse group of pathogenic organisms. Pathogen recognition is considered as the most critical step behind eliciting adequate immune response during an infection. Hitherto Toll-like receptors (TLRs), especially the surface ones viz. TLR2 and TLR4 have gained immense importance due to their extreme ability of identifying distinct molecular patterns from invading pathogens. These pattern recognition receptors (PRRs) not only act as innate sensor but also shape and bridge innate and adaptive immune responses. In addition, they also play a pivotal role in regulating the balance between Th1 and Th2 type of response essential for the survivability of the host. In this work, major achievements rather findings made on the typical signalling and immunopathological attributes of TLR2 and TLR4 mediated host response against the major infectious diseases have been reviewed. Infectious diseases like tuberculosis, trypanosomiasis, malaria, and filariasis are still posing myriad threat to mankind. Furthermore, increasing resistance of the causative organisms against available therapeutics is also an emerging problem. Thus, stimulation of host immune response with TLR2 and TLR4 agonist can be the option of choice to treat such diseases in future.}, } @article {pmid26774793, year = {2016}, author = {Soares, MP and Yilmaz, B}, title = {Microbiota Control of Malaria Transmission.}, journal = {Trends in parasitology}, volume = {32}, number = {2}, pages = {120-130}, doi = {10.1016/j.pt.2015.11.004}, pmid = {26774793}, issn = {1471-5007}, mesh = {Antibodies/immunology ; Biological Evolution ; Host-Pathogen Interactions/*immunology ; Humans ; Intestines/microbiology ; Malaria, Falciparum/immunology/*microbiology/prevention & control/*transmission ; Microbiota/immunology/*physiology ; Plasmodium falciparum/physiology ; Polysaccharides/immunology ; Protozoan Vaccines/immunology ; }, abstract = {Stable mutualistic interactions between multicellular organisms and microbes are an evolutionarily conserved process with a major impact on host physiology and fitness. Humans establish such interactions with a consortium of microorganisms known as the microbiota. Despite the mutualistic nature of these interactions, some bacterial components of the human microbiota express immunogenic glycans that elicit glycan-specific antibody (Ab) responses. The ensuing circulating Abs are protective against infections by pathogens that express those glycans, as demonstrated for Plasmodium, the causative agent of malaria. Presumably, a similar protective Ab response acts against other vector-borne diseases.}, } @article {pmid26761184, year = {2016}, author = {Chhetri, J and Gueven, N}, title = {Targeting mitochondrial function to protect against vision loss.}, journal = {Expert opinion on therapeutic targets}, volume = {20}, number = {6}, pages = {721-736}, doi = {10.1517/14728222.2015.1134489}, pmid = {26761184}, issn = {1744-7631}, mesh = {Animals ; Eye Diseases/etiology/*prevention & control ; Humans ; Mitochondria/metabolism/*pathology ; Mitochondrial Diseases/*complications/physiopathology ; Neurodegenerative Diseases/complications/physiopathology ; Vision Disorders/etiology/prevention & control ; }, abstract = {INTRODUCTION: Mitochondria, essential to multicellular life, convert food into ATP to satisfy cellular energy demands. Since different tissues have different energy requirements, mitochondrial density is high in tissues with high metabolic needs, such as the visual system, which is therefore highly susceptible to limited energy supply as a result of mitochondrial dysfunction.

AREAS COVERED: Vision impairment is a common feature of most mitochondrial diseases. At the same time, there is mounting evidence that mitochondrial impairment contributes to the pathogenesis of major eye diseases such as glaucoma and might also be involved in the reported vision impairment in neurodegenerative disorders such as Alzheimer's disease.

EXPERT OPINION: Rather than relying on symptomatic treatment, acknowledging the mitochondrial origin of visual disorders in mitochondrial, neurodegenerative and ocular diseases could lead to novel therapeutics that aim to modulate mitochondrial function in order to protect against vision loss. This approach has already shown some promising clinical results in inherited retinal disorders, which supports the idea that targeting mitochondria could also be a treatment option for other optic neuropathies.}, } @article {pmid26756664, year = {2016}, author = {Ambrose, BA and Vasco, A}, title = {Bringing the multicellular fern meristem into focus.}, journal = {The New phytologist}, volume = {210}, number = {3}, pages = {790-793}, doi = {10.1111/nph.13825}, pmid = {26756664}, issn = {1469-8137}, mesh = {Ferns/*cytology/genetics/metabolism ; Genes, Plant ; Meristem/*cytology/genetics/metabolism ; Phylogeny ; Plant Proteins/metabolism ; }, } @article {pmid26740169, year = {2016}, author = {Anderson, DP and Whitney, DS and Hanson-Smith, V and Woznica, A and Campodonico-Burnett, W and Volkman, BF and King, N and Thornton, JW and Prehoda, KE}, title = {Evolution of an ancient protein function involved in organized multicellularity in animals.}, journal = {eLife}, volume = {5}, number = {}, pages = {e10147}, pmid = {26740169}, issn = {2050-084X}, support = {UL1 TR000430/TR/NCATS NIH HHS/United States ; R01GM089977/GM/NIGMS NIH HHS/United States ; //Canadian Institutes of Health Research/Canada ; R01 GM087457/GM/NIGMS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R01 GM089977/GM/NIGMS NIH HHS/United States ; R01 GM104397/GM/NIGMS NIH HHS/United States ; R01GM087457/GM/NIGMS NIH HHS/United States ; R01GM104397/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Cell Cycle ; Cell Cycle Proteins/chemistry/*genetics/*metabolism ; *Evolution, Molecular ; Guanylate Kinases/chemistry/*genetics/*metabolism ; Models, Molecular ; Protein Binding ; Protein Multimerization ; Spindle Apparatus/*metabolism ; }, abstract = {To form and maintain organized tissues, multicellular organisms orient their mitotic spindles relative to neighboring cells. A molecular complex scaffolded by the GK protein-interaction domain (GKPID) mediates spindle orientation in diverse animal taxa by linking microtubule motor proteins to a marker protein on the cell cortex localized by external cues. Here we illuminate how this complex evolved and commandeered control of spindle orientation from a more ancient mechanism. The complex was assembled through a series of molecular exploitation events, one of which - the evolution of GKPID's capacity to bind the cortical marker protein - can be recapitulated by reintroducing a single historical substitution into the reconstructed ancestral GKPID. This change revealed and repurposed an ancient molecular surface that previously had a radically different function. We show how the physical simplicity of this binding interface enabled the evolution of a new protein function now essential to the biological complexity of many animals.}, } @article {pmid26738546, year = {2016}, author = {Maruta, T and Sawa, Y and Shigeoka, S and Ishikawa, T}, title = {Diversity and Evolution of Ascorbate Peroxidase Functions in Chloroplasts: More Than Just a Classical Antioxidant Enzyme?.}, journal = {Plant & cell physiology}, volume = {57}, number = {7}, pages = {1377-1386}, doi = {10.1093/pcp/pcv203}, pmid = {26738546}, issn = {1471-9053}, mesh = {Antioxidants/*metabolism ; Ascorbate Peroxidases/*metabolism ; Chloroplasts/*enzymology ; *Evolution, Molecular ; Oxidative Stress ; Signal Transduction ; }, abstract = {Reactive oxygen species (ROS) have dual functions in plant cells as cytotoxic molecules and emergency signals. The balance between the production and scavenging of these molecules in chloroplasts, major sites for the production of ROS, is one of the key determinants for plant acclimation to stress conditions. The water-water cycle is a crucial regulator of ROS levels in chloroplasts. In this cycle, the stromal and thylakoid membrane-attached isoforms of ascorbate peroxidase (sAPX and tAPX, respectively) are involved in the metabolism of H2O2 Current genome and phylogenetic analyses suggest that the first monofunctional APX was generated as sAPX in unicellular green algae, and that tAPX occurred in multicellular charophytes during plant evolution. Chloroplastic APXs, especially tAPX, have been considered to be the source of a bottleneck in the water-water cycle, at least in higher plants, because of their high susceptibility to H2O2 A number of studies have succeeded in improving plant stress resistance by reinforcing the fragile characteristics of the enzymes. However, researchers have unexpectedly failed to find a 'stress-sensitive phenotype' among loss-of-function mutants, at least in laboratory conditions. Interestingly, the susceptibility of enzymes to H2O2 may have been acquired during plant evolution, thereby allowing for the flexible use of H2O2 as a signaling molecule in plants, and this is supported by growing lines of evidence for the physiological significance of chloroplastic H2O2 as a retrograde signal in plant stress responses. By overviewing historical, biochemical, physiological and genetic studies, we herein discuss the diverse functions of chloroplastic APXs as antioxidant enzymes and signaling modulators.}, } @article {pmid26725198, year = {2016}, author = {Proust, H and Honkanen, S and Jones, VA and Morieri, G and Prescott, H and Kelly, S and Ishizaki, K and Kohchi, T and Dolan, L}, title = {RSL Class I Genes Controlled the Development of Epidermal Structures in the Common Ancestor of Land Plants.}, journal = {Current biology : CB}, volume = {26}, number = {1}, pages = {93-99}, pmid = {26725198}, issn = {1879-0445}, mesh = {Amino Acid Sequence ; Basic Helix-Loop-Helix Transcription Factors/*genetics/metabolism ; *Biological Evolution ; Bryophyta/genetics/growth & development ; Bryopsida/genetics ; Gene Expression Regulation, Plant ; *Genes, Plant ; Germ Cells, Plant/growth & development ; Indoleacetic Acids/metabolism ; Molecular Sequence Data ; Mutation ; Phylogeny ; Plant Epidermis/cytology/*genetics/*growth & development ; Plant Proteins/genetics/metabolism ; Plants, Genetically Modified ; Transcription Factors/metabolism ; }, abstract = {The colonization of the land by plants, sometime before 470 million years ago, was accompanied by the evolution tissue systems [1-3]. Specialized structures with diverse functions-from nutrient acquisition to reproduction-derived from single cells in the outermost layer (epidermis) were important sources of morphological innovation at this time [2, 4, 5]. In extant plants, these structures may be unicellular extensions, such as root hairs or rhizoids [6-9], or multicellular structures, such as asexual propagules or secretory hairs (papillae) [10-12]. Here, we show that a ROOTHAIR DEFECTIVE SIX-LIKE (RSL) class I basic helix-loop-helix transcription factor positively regulates the development of the unicellular and multicellular structures that develop from individual cells that expand out of the epidermal plane of the liverwort Marchantia polymorpha; mutants that lack MpRSL1 function do not develop rhizoids, slime papillae, mucilage papillae, or gemmae. Furthermore, we discovered that RSL class I genes are also required for the development of multicellular axillary hairs on the gametophyte of the moss Physcomitrella patens. Because class I RSL proteins also control the development of rhizoids in mosses and root hairs in angiosperms [13, 14], these data demonstrate that the function of RSL class I genes was to control the development of structures derived from single epidermal cells in the common ancestor of the land plants. Class I RSL genes therefore controlled the generation of adaptive morphological diversity as plants colonized the land from the water.}, } @article {pmid30183198, year = {2016}, author = {Savostyanov, GA}, title = {EMERGENCE OF STEM CELLS. THE DEVELOPMENT OF MULTICELLULARITY AND ITS QUANTITATIVE CHARACTERISTICS.}, journal = {Tsitologiia}, volume = {58}, number = {8}, pages = {577-593}, pmid = {30183198}, issn = {0041-3771}, mesh = {Biological Evolution ; *Models, Biological ; *Stem Cells ; }, abstract = {A new approach to the description of the stem cells emergence in the development of multicellular organisms has been proposed based on a formalized description of the formation of elementary units of multicellularity — «gistions» by purchasing and implementing potentials for implementation of the procedure of division of functions between the cells. The system of gistions is shown in the form of the periodic table, which allows to predict the structure of the development and to measure it. The laws of conservation potentialities in gistions were suggested, explaining the origin of the stem cells. For the quantitative characteristics of development the experimentally determined parameters were described. Using it one can not only find a common pool of potentials, but also divide them into separate species and, thus, to talk about the structure of the pool and characterize changes in its development.}, } @article {pmid29513353, year = {2016}, author = {Cummings, FW}, title = {Early metazoan development: the origin of the Cambrian exuberance.}, journal = {Theoretical biology forum}, volume = {109}, number = {1-2}, pages = {71-92}, doi = {10.19272/201611402005}, pmid = {29513353}, issn = {2282-2593}, mesh = {*Algorithms ; Animals ; *Biological Evolution ; Blastula/growth & development ; *Body Patterning ; Cell Movement ; Mesoderm/cytology/growth & development ; *Models, Biological ; Wnt Signaling Pathway ; }, abstract = {A number of common features can be observed in the earliest developing embryos of all animal phyla. A simple extant model of morphogenesis is outlined here, with the aim of giving a model of the relatively rapid appearance of Cambrian animals, 541-515 mya. Developmental patterning, elucidated by a simple linear model with only short-range diffusion of ligands, is given as the origin of the most primitive animals. The key aspect of the model involves the interaction between the emergence of the Wnt and Hedgehog (Hh) signaling pathways. The non-canonical Wnt pathway is crucial in first establishing a sphere of cells, by way of cell-cell connection fi bers. A mutation in the Wnt pathway at the dawn of multicellular organisms is argued to have given rise to the early Hh pathway, and their interaction gives two spatially separate gene determination regions, the key goal of biological patterning.}, } @article {pmid26715509, year = {2016}, author = {Lambropoulos, N and Garcia, A and Clarke, RJ}, title = {Stimulation of Na(+),K(+)-ATPase Activity as a Possible Driving Force in Cholesterol Evolution.}, journal = {The Journal of membrane biology}, volume = {249}, number = {3}, pages = {251-259}, pmid = {26715509}, issn = {1432-1424}, mesh = {Biological Evolution ; Cell Membrane/*metabolism ; Cholesterol/*metabolism ; Cytochromes c/genetics/metabolism ; Membrane Proteins/metabolism ; Oxidoreductases Acting on CH-CH Group Donors/genetics/metabolism ; Phylogeny ; Sodium-Potassium-Exchanging ATPase/genetics/*metabolism ; Squalene Monooxygenase/metabolism ; }, abstract = {Cholesterol is exclusively produced by animals and is present in the plasma membrane of all animal cells. In contrast, the membranes of fungi and plants contain other sterols. To explain the exclusive preference of animal cells for cholesterol, we propose that cholesterol may have evolved to optimize the activity of a crucial protein found in the plasma membrane of all multicellular animals, namely the Na(+),K(+)-ATPase. To test this hypothesis, mirror tree and phylogenetic distribution analyses have been conducted of the Na(+),K(+)-ATPase and 3β-hydroxysterol Δ(24)-reductase (DHCR24), the last enzyme in the Bloch cholesterol biosynthetic pathway. The results obtained support the hypothesis of a co-evolution of the Na(+),K(+)-ATPase and DHCR24. The evolutionary correlation between DHCR24 and the Na(+),K(+)-ATPase was found to be stronger than between DHCR24 and any other membrane protein investigated. The results obtained, thus, also support the hypothesis that cholesterol evolved together with the Na(+),K(+)-ATPase in multicellular animals to support Na(+),K(+)-ATPase activity.}, } @article {pmid26714637, year = {2015}, author = {Pan, Y and Bo, K and Cheng, Z and Weng, Y}, title = {The loss-of-function GLABROUS 3 mutation in cucumber is due to LTR-retrotransposon insertion in a class IV HD-ZIP transcription factor gene CsGL3 that is epistatic over CsGL1.}, journal = {BMC plant biology}, volume = {15}, number = {}, pages = {302}, pmid = {26714637}, issn = {1471-2229}, mesh = {Cucumis sativus/*genetics/growth & development/metabolism ; Epistasis, Genetic ; *Gene Expression Regulation, Plant ; Molecular Sequence Data ; Organogenesis, Plant ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Retroelements ; Terminal Repeat Sequences ; Transcription Factors/*genetics/metabolism ; Trichomes/growth & development ; }, abstract = {BACKGROUND: Trichomes, developed from the protodermal cells (the outermost cell layer of the embryo), are hair-like structures covering the aerial parts of plants. The genetic network regulating trichome development has been extensively studied and well understood in the model species Arabidopsis thaliana, which bears unicellular, non-glandular and branched trichomes. However, little is known about the genetic and molecular basis of organogenesis of multi-cellular trichomes in plant species like cucumber (Cucumis sativus L.), which are likely different from Arabidopsis.

RESULTS: We identified a new trichome mutant in cucumber which exhibited a completely glabrous phenotype on all aerial organs. Genetic analysis indicated that the glabrous phenotype was inherited as a single recessive gene, csgl3. Fine genetic mapping delimited the csgl3 locus into a 68.4 kb region with 12 predicted genes. Genetic analysis, sequence alignment and allelic variation survey in natural populations identified Csa6G514870 encoding a class IV homeodomain-associated leucine zipper (HD-ZIP) transcription factor as the only candidate for CsGL3, which was 5188 bp in length with 10 predicted exons. Gene expression analysis revealed the loss-of-function of CsGL3 in the mutant due to the insertion of a 5-kb long terminal repeat (LTR) retrotransposon in the 4th exon of CsGL3. Linkage analysis in a segregating population and gene expression analysis of the CsGL1 and CsGL3 genes in csgl1, csgl3, and csgl1 + 3 genetic backgrounds uncovered interactions between the two genes. Phylogenetic analysis among 28 class IV HD-ZIP protein sequences from five species placed cucumber CsGL3 into the same clade with 7 other members that play important roles in trichome initiation.

CONCLUSIONS: The new glabrous mutation in cucumber was controlled by a single recessive locus csgl3, which was phenotypically and genetically distinct from two previously reported glabrous mutants csgl1 and csgl2. The glabrous phenotype in csgl3 was due to insertion of an autonomous, active, class I transposable element in CsGL3, a class IV HD-ZIP transcription factor. CsGL3 was epistatic to CsGL1. CsGL3 seemed to play important roles in cucumber trichome initiation whereas CsGL1 may act downstream in the trichome development pathway(s). Findings from the present study provide new insights into genetic control of trichome development in cucumber.}, } @article {pmid26714105, year = {2015}, author = {Shou, W}, title = {Acknowledging selection at sub-organismal levels resolves controversy on pro-cooperation mechanisms.}, journal = {eLife}, volume = {4}, number = {}, pages = {}, pmid = {26714105}, issn = {2050-084X}, mesh = {*Biological Evolution ; Eukaryota ; *Symbiosis ; }, abstract = {Cooperators who pay a cost to produce publically-available benefits can be exploited by cheaters who do not contribute fairly. How might cooperation persist against cheaters? Two classes of mechanisms are known to promote cooperation: 'partner choice', where a cooperator preferentially interacts with cooperative over cheating partners; and 'partner fidelity feedback', where repeated interactions between individuals ensure that cheaters suffer as their cooperative partners languish (see, for example, Momeni et al., 2013). However when both mechanisms can act, differentiating them has generated controversy. Here, I resolve this controversy by noting that selection can operate on organismal and sub-organismal 'entities' such that partner fidelity feedback at sub-organismal level can appear as partner choice at organismal level. I also show that cooperation between multicellular eukaryotes and mitochondria is promoted by partner fidelity feedback and partner choice between sub-organismal entities, in addition to being promoted by partner fidelity feedback between hosts and symbionts, as was previously known.}, } @article {pmid26712697, year = {2016}, author = {Pomin, VH}, title = {Phylogeny, structure, function, biosynthesis and evolution of sulfated galactose-containing glycans.}, journal = {International journal of biological macromolecules}, volume = {84}, number = {}, pages = {372-379}, doi = {10.1016/j.ijbiomac.2015.12.035}, pmid = {26712697}, issn = {1879-0003}, mesh = {Aquatic Organisms/classification/genetics/metabolism ; Biological Evolution ; Carbohydrate Metabolism ; Carbohydrates/chemistry ; Galactose/*chemistry ; Molecular Structure ; Phylogeny ; Polysaccharides/*biosynthesis/*chemistry ; Structure-Activity Relationship ; Sulfates/*chemistry ; }, abstract = {Glycans are ubiquitous components of all organisms. The specificity of glycan structures works in molecular recognition in multiple biological processes especially cell-cell and cell-matrix signaling events. These events are mostly driven by functional proteins whose activities are ultimately regulated by interactions with carbohydrate moieties of cell surface glycoconjugates. Galactose is a common composing monosaccharide in glycoconjugates. Sulfation at certain positions of the galactose residues does not only increase affinity for some binding proteins but also makes the structures of the controlling glycans more specific to molecular interactions. Here the phylogenetic distribution of glycans containing the sulfated galactose unit is examined across numerous multicellular organisms. Analysis includes autotrophs and heterotrophs from both terrestrial and marine environments. Information exists more regarding the marine species. Although future investigations in molecular biology must be still performed in order to assure certain hypotheses, empirical evidences based on structural biology of the sulfated galactose-containing glycans among different species particularly their backbone and sulfation patterns clearly indicate great specificity in terms of glycosyltransferase and sulfotransferase activity. This set of information suggests that evolution has shaped the biosynthetic machinery of these glycans somewhat related to their potential functions in the organisms.}, } @article {pmid26709836, year = {2016}, author = {Mallet, J and Besansky, N and Hahn, MW}, title = {How reticulated are species?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {38}, number = {2}, pages = {140-149}, pmid = {26709836}, issn = {1521-1878}, support = {BB/G006903/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; R01 AI076584/AI/NIAID NIH HHS/United States ; R01 AI76584/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Eukaryota/genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; *Genetic Speciation ; Genomics/methods ; Organisms, Genetically Modified/genetics ; *Phylogeny ; Plants/genetics ; }, abstract = {Many groups of closely related species have reticulate phylogenies. Recent genomic analyses are showing this in many insects and vertebrates, as well as in microbes and plants. In microbes, lateral gene transfer is the dominant process that spoils strictly tree-like phylogenies, but in multicellular eukaryotes hybridization and introgression among related species is probably more important. Because many species, including the ancestors of ancient major lineages, seem to evolve rapidly in adaptive radiations, some sexual compatibility may exist among them. Introgression and reticulation can thereby affect all parts of the tree of life, not just the recent species at the tips. Our understanding of adaptive evolution, speciation, phylogenetics, and comparative biology must adapt to these mostly recent findings. Introgression has important practical implications as well, not least for the management of genetically modified organisms in pest and disease control.}, } @article {pmid26709324, year = {2016}, author = {Ryan, PA and Powers, ST and Watson, RA}, title = {Social niche construction and evolutionary transitions in individuality.}, journal = {Biology & philosophy}, volume = {31}, number = {}, pages = {59-79}, pmid = {26709324}, issn = {0169-3867}, abstract = {Social evolution theory conventionally takes an externalist explanatory stance, treating observed cooperation as explanandum and the positive assortment of cooperative behaviour as explanans. We ask how the circumstances bringing about this positive assortment arose in the first place. Rather than merely push the explanatory problem back a step, we move from an externalist to an interactionist explanatory stance, in the spirit of Lewontin and the Niche Construction theorists. We develop a theory of 'social niche construction' in which we consider biological entities to be both the subject and object of their own social evolution. Some important cases of the evolution of cooperation have the side-effect of causing changes in the hierarchical level at which the evolutionary process acts. This is because the traits (e.g. life-history bottlenecks) that act to align the fitness interests of particles (e.g. cells) in a collective can also act to diminish the extent to which those particles are bearers of heritable fitness variance, while augmenting the extent to which collectives of such particles (e.g. multicellular organisms) are bearers of heritable fitness variance. In this way, we can explain upward transitions in the hierarchical level at which the Darwinian machine operates in terms of particle-level selection, even though the outcome of the process is a collective-level selection regime. Our theory avoids the logical and metaphysical paradoxes faced by other attempts to explain evolutionary transitions.}, } @article {pmid26704468, year = {2016}, author = {McCoy-Simandle, K and Hanna, SJ and Cox, D}, title = {Exosomes and nanotubes: Control of immune cell communication.}, journal = {The international journal of biochemistry & cell biology}, volume = {71}, number = {}, pages = {44-54}, pmid = {26704468}, issn = {1878-5875}, support = {P01 CA100324/CA/NCI NIH HHS/United States ; K12GM102779/GM/NIGMS NIH HHS/United States ; K12 GM102779/GM/NIGMS NIH HHS/United States ; R01 GM071828/GM/NIGMS NIH HHS/United States ; P30 CA013330/CA/NCI NIH HHS/United States ; }, mesh = {Cell Communication/*immunology ; Exosomes/*metabolism ; Humans ; }, abstract = {Cell-cell communication is critical to coordinate the activity and behavior of a multicellular organism. The cells of the immune system not only must communicate with similar cells, but also with many other cell types in the body. Therefore, the cells of the immune system have evolved multiple ways to communicate. Exosomes and tunneling nanotubes (TNTs) are two means of communication used by immune cells that contribute to immune functions. Exosomes are small membrane vesicles secreted by most cell types that can mediate intercellular communication and in the immune system they are proposed to play a role in antigen presentation and modulation of gene expression. TNTs are membranous structures that mediate direct cell-cell contact over several cell diameters in length (and possibly longer) and facilitate the interaction and/or the transfer of signals, material and other cellular organelles between connected cells. Recent studies have revealed additional, but sometimes conflicting, structural and functional features of both exosomes and TNTs. Despite the new and exciting information in exosome and TNT composition, origin and in vitro function, biologically significant functions are still being investigated and determined. In this review, we discuss the current field regarding exosomes and TNTs in immune cells providing evaluation and perspectives of the current literature.}, } @article {pmid26695632, year = {2015}, author = {Dewachter, L and Verstraeten, N and Monteyne, D and Kint, CI and Versées, W and Pérez-Morga, D and Michiels, J and Fauvart, M}, title = {A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in Escherichia coli.}, journal = {mBio}, volume = {6}, number = {6}, pages = {e01935-15}, pmid = {26695632}, issn = {2150-7511}, mesh = {*Amino Acid Substitution ; *Apoptosis ; DNA Fragmentation ; Escherichia coli/genetics/*physiology ; Escherichia coli Proteins/*genetics/*metabolism ; Membrane Potentials ; Microbial Viability ; Monomeric GTP-Binding Proteins/*genetics/*metabolism ; Mutant Proteins/genetics/metabolism ; Phosphatidylserines/analysis ; }, abstract = {UNLABELLED: Programmed cell death (PCD) is an important hallmark of multicellular organisms. Cells self-destruct through a regulated series of events for the benefit of the organism as a whole. The existence of PCD in bacteria has long been controversial due to the widely held belief that only multicellular organisms would profit from this kind of altruistic behavior at the cellular level. However, over the past decade, compelling experimental evidence has established the existence of such pathways in bacteria. Here, we report that expression of a mutant isoform of the essential GTPase ObgE causes rapid loss of viability in Escherichia coli. The physiological changes that occur upon expression of this mutant protein--including loss of membrane potential, chromosome condensation and fragmentation, exposure of phosphatidylserine on the cell surface, and membrane blebbing--point to a PCD mechanism. Importantly, key regulators and executioners of known bacterial PCD pathways were shown not to influence this cell death program. Collectively, our results suggest that the cell death pathway described in this work constitutes a new mode of bacterial PCD.

IMPORTANCE: Programmed cell death (PCD) is a well-known phenomenon in higher eukaryotes. In these organisms, PCD is essential for embryonic development--for example, the disappearance of the interdigital web--and also functions in tissue homeostasis and elimination of pathogen-invaded cells. The existence of PCD mechanisms in unicellular organisms like bacteria, on the other hand, has only recently begun to be recognized. We here demonstrate the existence of a bacterial PCD pathway that induces characteristics that are strikingly reminiscent of eukaryotic apoptosis, such as fragmentation of DNA, exposure of phosphatidylserine on the cell surface, and membrane blebbing. Our results can provide more insight into the mechanism and evolution of PCD pathways in higher eukaryotes. More importantly, especially in the light of the looming antibiotic crisis, they may point to a bacterial Achilles' heel and can inspire innovative ways of combating bacterial infections, directed at the targeted activation of PCD pathways.}, } @article {pmid26667994, year = {2016}, author = {Hervé, C and Siméon, A and Jam, M and Cassin, A and Johnson, KL and Salmeán, AA and Willats, WG and Doblin, MS and Bacic, A and Kloareg, B}, title = {Arabinogalactan proteins have deep roots in eukaryotes: identification of genes and epitopes in brown algae and their role in Fucus serratus embryo development.}, journal = {The New phytologist}, volume = {209}, number = {4}, pages = {1428-1441}, doi = {10.1111/nph.13786}, pmid = {26667994}, issn = {1469-8137}, mesh = {Amino Acid Sequence ; Cell Division/radiation effects ; Cell Wall/metabolism/radiation effects ; Epitopes/*metabolism ; Fucus/*genetics/*growth & development/radiation effects ; Genes, Plant ; Genome ; Indicators and Reagents ; Light ; Models, Biological ; Mucoproteins/chemistry/*metabolism ; Phylogeny ; Plant Proteins/chemistry/metabolism ; Protein Domains ; Sequence Homology, Nucleic Acid ; Zygote/metabolism ; }, abstract = {Arabinogalactan proteins (AGPs) are highly glycosylated, hydroxyproline-rich proteins found at the cell surface of plants, where they play key roles in developmental processes. Brown algae are marine, multicellular, photosynthetic eukaryotes. They belong to the phylum Stramenopiles, which is unrelated to land plants and green algae (Chloroplastida). Brown algae share common evolutionary features with other multicellular organisms, including a carbohydrate-rich cell wall. They differ markedly from plants in their cell wall composition, and AGPs have not been reported in brown algae. Here we investigated the presence of chimeric AGP-like core proteins in this lineage. We report that the genome sequence of the brown algal model Ectocarpus siliculosus encodes AGP protein backbone motifs, in a gene context that differs considerably from what is known in land plants. We showed the occurrence of AGP glycan epitopes in a range of brown algal cell wall extracts. We demonstrated that these chimeric AGP-like core proteins are developmentally regulated in embryos of the order Fucales and showed that AGP loss of function seriously impairs the course of early embryogenesis. Our findings shine a new light on the role of AGPs in cell wall sensing and raise questions about the origin and evolution of AGPs in eukaryotes.}, } @article {pmid26667648, year = {2015}, author = {Hugerth, LW and Larsson, J and Alneberg, J and Lindh, MV and Legrand, C and Pinhassi, J and Andersson, AF}, title = {Metagenome-assembled genomes uncover a global brackish microbiome.}, journal = {Genome biology}, volume = {16}, number = {}, pages = {279}, pmid = {26667648}, issn = {1474-760X}, mesh = {Bacteria/genetics ; *Genome, Bacterial ; *Metagenome ; Microbiota/*genetics ; Oceans and Seas ; Phylogeny ; Phylogeography ; Plankton/*genetics ; Seasons ; Seawater/*microbiology ; }, abstract = {BACKGROUND: Microbes are main drivers of biogeochemical cycles in oceans and lakes. Although the genome is a foundation for understanding the metabolism, ecology and evolution of an organism, few bacterioplankton genomes have been sequenced, partly due to difficulties in cultivating them.

RESULTS: We use automatic binning to reconstruct a large number of bacterioplankton genomes from a metagenomic time-series from the Baltic Sea, one of world's largest brackish water bodies. These genomes represent novel species within typical freshwater and marine clades, including clades not previously sequenced. The genomes' seasonal dynamics follow phylogenetic patterns, but with fine-grained lineage-specific variations, reflected in gene-content. Signs of streamlining are evident in most genomes, and estimated genome sizes correlate with abundance variation across filter size fractions. Comparing the genomes with globally distributed metagenomes reveals significant fragment recruitment at high sequence identity from brackish waters in North America, but little from lakes or oceans. This suggests the existence of a global brackish metacommunity whose populations diverged from freshwater and marine relatives over 100,000 years ago, long before the Baltic Sea was formed (8000 years ago). This markedly contrasts to most Baltic Sea multicellular organisms, which are locally adapted populations of freshwater or marine counterparts.

CONCLUSIONS: We describe the gene content, temporal dynamics and biogeography of a large set of new bacterioplankton genomes assembled from metagenomes. We propose that brackish environments exert such strong selection that lineages adapted to them flourish globally with limited influence from surrounding aquatic communities.}, } @article {pmid26663204, year = {2016}, author = {Fisher, RM and Bell, T and West, SA}, title = {Multicellular group formation in response to predators in the alga Chlorella vulgaris.}, journal = {Journal of evolutionary biology}, volume = {29}, number = {3}, pages = {551-559}, doi = {10.1111/jeb.12804}, pmid = {26663204}, issn = {1420-9101}, mesh = {Animals ; Biological Evolution ; Chlorella vulgaris/*physiology ; Predatory Behavior ; Tetrahymena thermophila/*physiology ; }, abstract = {A key step in the evolution of multicellular organisms is the formation of cooperative multicellular groups. It has been suggested that predation pressure may promote multicellular group formation in some algae and bacteria, with cells forming groups to lower their chance of being eaten. We use the green alga Chlorella vulgaris and the protist Tetrahymena thermophila to test whether predation pressure can initiate the formation of colonies. We found that: (1) either predators or just predator exoproducts promote colony formation; (2) higher predator densities cause more colonies to form; and (3) colony formation in this system is facultative, with populations returning to being unicellular when the predation pressure is removed. These results provide empirical support for the hypothesis that predation pressure promotes multicellular group formation. The speed of the reversion of populations to unicellularity suggests that this response is due to phenotypic plasticity and not evolutionary change.}, } @article {pmid26655898, year = {2015}, author = {Sugihara, K and Nishiyama, K and Fukuhara, S and Uemura, A and Arima, S and Kobayashi, R and Köhn-Luque, A and Mochizuki, N and Suda, T and Ogawa, H and Kurihara, H}, title = {Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling.}, journal = {Cell reports}, volume = {13}, number = {9}, pages = {1814-1827}, doi = {10.1016/j.celrep.2015.10.051}, pmid = {26655898}, issn = {2211-1247}, mesh = {Animals ; Aorta/cytology/metabolism ; Cell Movement/drug effects ; Embryo, Nonmammalian/metabolism ; Endothelial Cells/drug effects/metabolism ; Mice ; Mice, Inbred C57BL ; *Models, Biological ; Neovascularization, Physiologic/drug effects ; Retina/drug effects/metabolism ; Time-Lapse Imaging ; Vascular Endothelial Growth Factor A/pharmacology ; Zebrafish/growth & development ; }, abstract = {Angiogenesis is a multicellular phenomenon driven by morphogenetic cell movements. We recently reported morphogenetic vascular endothelial cell (EC) behaviors to be dynamic and complex. However, the principal mechanisms orchestrating individual EC movements in angiogenic morphogenesis remain largely unknown. Here we present an experiment-driven mathematical model that enables us to systematically dissect cellular mechanisms in branch elongation. We found that cell-autonomous and coordinated actions governed these multicellular behaviors, and a cell-autonomous process sufficiently illustrated essential features of the morphogenetic EC dynamics at both the single-cell and cell-population levels. Through refining our model and experimental verification, we further identified a coordinated mode of tip EC behaviors regulated via a spatial relationship between tip and follower ECs, which facilitates the forward motility of tip ECs. These findings provide insights that enhance our mechanistic understanding of not only angiogenic morphogenesis, but also other types of multicellular phenomenon.}, } @article {pmid26648040, year = {2015}, author = {Longo, G and Montevil, M and Sonnenschein, C and Soto, AM}, title = {In search of principles for a Theory of Organisms.}, journal = {Journal of biosciences}, volume = {40}, number = {5}, pages = {955-968}, pmid = {26648040}, issn = {0973-7138}, support = {R01 ES008314/ES/NIEHS NIH HHS/United States ; U01 ES020888/ES/NIEHS NIH HHS/United States ; ES08314/ES/NIEHS NIH HHS/United States ; U01-ES020888/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Biophysics/methods ; Cell Division ; Mice, Inbred C57BL ; *Models, Biological ; *Morphogenesis ; Physics/methods ; Thermodynamics ; }, abstract = {Lacking an operational theory to explain the organization and behaviour of matter in unicellular and multicellular organisms hinders progress in biology. Such a theory should address life cycles from ontogenesis to death. This theory would complement the theory of evolution that addresses phylogenesis, and would posit theoretical extensions to accepted physical principles and default states in order to grasp the living state of matter and define proper biological observables. Thus, we favour adopting the default state implicit in Darwin's theory, namely, cell proliferation with variation plus motility, and a framing principle, namely, life phenomena manifest themselves as non-identical iterations of morphogenetic processes. From this perspective, organisms become a consequence of the inherent variability generated by proliferation, motility and self-organization. Morphogenesis would then be the result of the default state plus physical constraints, like gravity, and those present in living organisms, like muscular tension.}, } @article {pmid26644562, year = {2015}, author = {Alié, A and Hayashi, T and Sugimura, I and Manuel, M and Sugano, W and Mano, A and Satoh, N and Agata, K and Funayama, N}, title = {The ancestral gene repertoire of animal stem cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {51}, pages = {E7093-100}, pmid = {26644562}, issn = {1091-6490}, mesh = {Animals ; Evolution, Molecular ; Genomic Instability ; Hydra/cytology/genetics ; Mammals ; Phylogeny ; Porifera/cytology/genetics ; RNA, Small Interfering/genetics ; RNA-Binding Proteins/genetics ; Stem Cells/*metabolism ; Transcription Factors/genetics ; Transcriptome ; }, abstract = {Stem cells are pivotal for development and tissue homeostasis of multicellular animals, and the quest for a gene toolkit associated with the emergence of stem cells in a common ancestor of all metazoans remains a major challenge for evolutionary biology. We reconstructed the conserved gene repertoire of animal stem cells by transcriptomic profiling of totipotent archeocytes in the demosponge Ephydatia fluviatilis and by tracing shared molecular signatures with flatworm and Hydra stem cells. Phylostratigraphy analyses indicated that most of these stem-cell genes predate animal origin, with only few metazoan innovations, notably including several partners of the Piwi machinery known to promote genome stability. The ancestral stem-cell transcriptome is strikingly poor in transcription factors. Instead, it is rich in RNA regulatory actors, including components of the "germ-line multipotency program" and many RNA-binding proteins known as critical regulators of mammalian embryonic stem cells.}, } @article {pmid26644561, year = {2015}, author = {Schaible, R and Scheuerlein, A and Dańko, MJ and Gampe, J and Martínez, DE and Vaupel, JW}, title = {Constant mortality and fertility over age in Hydra.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {51}, pages = {15701-15706}, pmid = {26644561}, issn = {1091-6490}, support = {R01 AG037965/AG/NIA NIH HHS/United States ; AG037965/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Fertility ; Hydra/*physiology ; Life Expectancy ; }, abstract = {Senescence, the increase in mortality and decline in fertility with age after maturity, was thought to be inevitable for all multicellular species capable of repeated breeding. Recent theoretical advances and compilations of data suggest that mortality and fertility trajectories can go up or down, or remain constant with age, but the data are scanty and problematic. Here, we present compelling evidence for constant age-specific death and reproduction rates in Hydra, a basal metazoan, in a set of experiments comprising more than 3.9 million days of observations of individual Hydra. Our data show that 2,256 Hydra from two closely related species in two laboratories in 12 cohorts, with cohort age ranging from 0 to more than 41 y, have extremely low, constant rates of mortality. Fertility rates for Hydra did not systematically decline with advancing age. This falsifies the universality of the theories of the evolution of aging that posit that all species deteriorate with age after maturity. The nonsenescent life history of Hydra implies levels of maintenance and repair that are sufficient to prevent the accumulation of damage for at least decades after maturity, far longer than the short life expectancy of Hydra in the wild. A high proportion of stem cells, constant and rapid cell turnover, few cell types, a simple body plan, and the fact that the germ line is not segregated from the soma are characteristics of Hydra that may make nonsenescence feasible. Nonsenescence may be optimal because lifetime reproduction may be enhanced more by extending adult life spans than by increasing daily fertility.}, } @article {pmid26638678, year = {2015}, author = {Libertini, G}, title = {Phylogeny of Aging and Related Phenoptotic Phenomena.}, journal = {Biochemistry. Biokhimiia}, volume = {80}, number = {12}, pages = {1529-1546}, doi = {10.1134/S0006297915120019}, pmid = {26638678}, issn = {1608-3040}, mesh = {Aging/*genetics ; Animals ; Apoptosis/physiology ; Biological Evolution ; DNA/genetics ; Humans ; Phylogeny ; Telomere/genetics ; }, abstract = {The interpretation of aging as adaptive, i.e. as a phenomenon genetically determined and modulated, and with an evolutionary advantage, implies that aging, as any physiologic mechanism, must have phylogenetic connections with similar phenomena. This review tries to find the phylogenetic connections between vertebrate aging and some related phenomena in other species, especially within those phenomena defined as phenoptotic, i.e. involving the death of one or more individuals for the benefit of other individuals. In particular, the aim of the work is to highlight and analyze similarities and connections, in the mechanisms and in the evolutionary causes, between: (i) proapoptosis in prokaryotes and apoptosis in unicellular eukaryotes; (ii) apoptosis in unicellular and multicellular eukaryotes; (iii) aging in yeast and in vertebrates; and (iv) the critical importance of the DNA subtelomeric segment in unicellular and multicellular eukaryotes. In short, there is strong evidence that vertebrate aging has clear similarities and connections with phenomena present in organisms with simpler organization. These phylogenetic connections are a necessary element for the sustainability of the thesis of aging explained as an adaptive phenomenon, and, on the contrary, are incompatible with the opposite view of aging as being due to the accumulation of random damages of various kinds.}, } @article {pmid26637532, year = {2015}, author = {Igaki, T}, title = {Communicating the molecular basis of cancer cell-by-cell: an interview with Tatsushi Igaki.}, journal = {Disease models & mechanisms}, volume = {8}, number = {12}, pages = {1491-1494}, doi = {10.1242/dmm.024059}, pmid = {26637532}, issn = {1754-8411}, mesh = {Animals ; Apoptosis ; Cell Communication ; Drosophila/cytology ; History, 20th Century ; History, 21st Century ; Humans ; Japan ; Neoplasms/*history ; }, abstract = {Tatsushi Igaki is currently based at the Kyoto University Graduate School of Biostudies, where he leads a research group dedicated to using Drosophila genetics to build a picture of the cell-cell communications underlying the establishment and maintenance of multicellular systems. His work has provided insight into the molecular bases of cell competition in the context of development and tumorigenesis, including the landmark discovery that oncogenic cells communicate with normal cells in the tumor microenvironment to induce tumor progression in a non-autonomous fashion. In this interview, he describes his career path, highlighting the shift in his research focus from the basic principles of apoptosis to clonal evolution in cancer, and also explains why Drosophila provides a powerful model system for studying cancer biology.}, } @article {pmid26636317, year = {2016}, author = {Li, XQ}, title = {Natural Attributes and Agricultural Implications of Somatic Genome Variation.}, journal = {Current issues in molecular biology}, volume = {20}, number = {}, pages = {29-46}, pmid = {26636317}, issn = {1467-3045}, mesh = {Agriculture ; Animals ; Evolution, Molecular ; *Genetic Variation ; Genome ; Humans ; Livestock/*genetics ; Models, Genetic ; Mutation ; Ploidies ; }, abstract = {This article proposes the concept of genome network, describes different variations of the somatic genome network, and reviews the agricultural implications of such variations. All genetic materials in a cell constitute the genome network of the cell and can jointly influence the cell's function and fate. The somatic genome of a plant is the genome network of cells in somatic tissues and of nonreproductive cells in pollen and ovules. Somatic genome variation (SGV, approximately equivalent to somagenetic variation) occurs at multiple levels, including stoichiometric, ploidy, and sequence variations. For a multicellular organism, the term "somatic genome variation" covers both the variation in part of the organism and the generation of new genotype individuals through somatic means from a sexually produced original genotype. For unicellular organisms, genome variation in somatic nuclei occurs at the whole organism level because there is only a single cell per individual. Growth, development and evolution of living organisms require both stability and instability of their genomes. Somatic genome variation displays many more attributes than genetic mutation and has strong implications for agriculture.}, } @article {pmid26634291, year = {2016}, author = {Boehm, CR and Ueda, M and Nishimura, Y and Shikanai, T and Haseloff, J}, title = {A Cyan Fluorescent Reporter Expressed from the Chloroplast Genome of Marchantia polymorpha.}, journal = {Plant & cell physiology}, volume = {57}, number = {2}, pages = {291-299}, pmid = {26634291}, issn = {1471-9053}, support = {BB/F011458/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L014130/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Base Sequence ; Fluorescence ; *Genome, Chloroplast ; Green Fluorescent Proteins/chemistry/genetics/*metabolism ; Marchantia/*genetics ; Molecular Sequence Data ; Plants, Genetically Modified ; Transformation, Genetic ; }, abstract = {Recently, the liverwort Marchantia polymorpha has received increasing attention as a basal plant model for multicellular studies. Its ease of handling, well-characterized plastome and proven protocols for biolistic plastid transformation qualify M. polymorpha as an attractive platform to study the evolution of chloroplasts during the transition from water to land. In addition, chloroplasts of M. polymorpha provide a convenient test-bed for the characterization of genetic elements involved in plastid gene expression due to the absence of mechanisms for RNA editing. While reporter genes have proven valuable to the qualitative and quantitative study of gene expression in chloroplasts, expression of green fluorescent protein (GFP) in chloroplasts of M. polymorpha has proven problematic. We report the design of a codon-optimized gfp varian, mturq2cp, which allowed successful expression of a cyan fluorescent protein under control of the tobacco psbA promoter from the chloroplast genome of M. polymorpha. We demonstrate the utility of mturq2cp in (i) early screening for transplastomic events following biolistic transformation of M. polymorpha spores; (ii) visualization of stromules as elements of plastid structure in Marchantia; and (iii) quantitative microscopy for the analysis of promoter activity.}, } @article {pmid26627241, year = {2015}, author = {Chang, ES and Neuhof, M and Rubinstein, ND and Diamant, A and Philippe, H and Huchon, D and Cartwright, P}, title = {Genomic insights into the evolutionary origin of Myxozoa within Cnidaria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {48}, pages = {14912-14917}, pmid = {26627241}, issn = {1091-6490}, mesh = {Animals ; *Evolution, Molecular ; *Genome ; Genomics ; Myxobolus/*genetics ; *Phylogeny ; Polypodium/parasitology ; }, abstract = {The Myxozoa comprise over 2,000 species of microscopic obligate parasites that use both invertebrate and vertebrate hosts as part of their life cycle. Although the evolutionary origin of myxozoans has been elusive, a close relationship with cnidarians, a group that includes corals, sea anemones, jellyfish, and hydroids, is supported by some phylogenetic studies and the observation that the distinctive myxozoan structure, the polar capsule, is remarkably similar to the stinging structures (nematocysts) in cnidarians. To gain insight into the extreme evolutionary transition from a free-living cnidarian to a microscopic endoparasite, we analyzed genomic and transcriptomic assemblies from two distantly related myxozoan species, Kudoa iwatai and Myxobolus cerebralis, and compared these to the transcriptome and genome of the less reduced cnidarian parasite, Polypodium hydriforme. A phylogenomic analysis, using for the first time to our knowledge, a taxonomic sampling that represents the breadth of myxozoan diversity, including four newly generated myxozoan assemblies, confirms that myxozoans are cnidarians and are a sister taxon to P. hydriforme. Estimations of genome size reveal that myxozoans have one of the smallest reported animal genomes. Gene enrichment analyses show depletion of expressed genes in categories related to development, cell differentiation, and cell-cell communication. In addition, a search for candidate genes indicates that myxozoans lack key elements of signaling pathways and transcriptional factors important for multicellular development. Our results suggest that the degeneration of the myxozoan body plan from a free-living cnidarian to a microscopic parasitic cnidarian was accompanied by extreme reduction in genome size and gene content.}, } @article {pmid26610912, year = {2015}, author = {Mao, M and Alavi, MV and Labelle-Dumais, C and Gould, DB}, title = {Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms.}, journal = {Current topics in membranes}, volume = {76}, number = {}, pages = {61-116}, doi = {10.1016/bs.ctm.2015.09.002}, pmid = {26610912}, issn = {1063-5823}, mesh = {Animals ; Basement Membrane/metabolism/*pathology ; *Cell Biology ; *Collagen Type IV/chemistry/genetics/metabolism ; *Disease ; Genomics ; Humans ; }, abstract = {Basement membranes are highly specialized extracellular matrices. Once considered inert scaffolds, basement membranes are now viewed as dynamic and versatile environments that modulate cellular behaviors to regulate tissue development, function, and repair. Increasing evidence suggests that, in addition to providing structural support to neighboring cells, basement membranes serve as reservoirs of growth factors that direct and fine-tune cellular functions. Type IV collagens are a major component of all basement membranes. They evolved along with the earliest multicellular organisms and have been integrated into diverse fundamental biological processes as time and evolution shaped the animal kingdom. The roles of basement membranes in humans are as complex and diverse as their distributions and molecular composition. As a result, basement membrane defects result in multisystem disorders with ambiguous and overlapping boundaries that likely reflect the simultaneous interplay and integration of multiple cellular pathways and processes. Consequently, there will be no single treatment for basement membrane disorders, and therapies are likely to be as varied as the phenotypes. Understanding tissue-specific pathology and the underlying molecular mechanism is the present challenge; personalized medicine will rely upon understanding how a given mutation impacts diverse cellular functions.}, } @article {pmid26609133, year = {2016}, author = {Cournac, A and Koszul, R and Mozziconacci, J}, title = {The 3D folding of metazoan genomes correlates with the association of similar repetitive elements.}, journal = {Nucleic acids research}, volume = {44}, number = {1}, pages = {245-255}, pmid = {26609133}, issn = {1362-4962}, support = {260822/ERC_/European Research Council/International ; }, mesh = {Animals ; Binding Sites ; Cell Nucleus ; Chromosome Mapping ; Chromosomes ; Computational Biology/methods ; Drosophila ; Embryonic Stem Cells/metabolism ; Evolution, Molecular ; *Genome ; Humans ; Mice ; Molecular Sequence Annotation ; *Nucleic Acid Conformation ; Organ Specificity/genetics ; Protein Binding ; *Repetitive Sequences, Nucleic Acid ; Transcription Factors/metabolism ; }, abstract = {The potential roles of the numerous repetitive elements found in the genomes of multi-cellular organisms remain speculative. Several studies have suggested a role in stabilizing specific 3D genomic contacts. To test this hypothesis, we exploited inter-chromosomal contacts frequencies obtained from Hi-C experiments and show that the folding of the human, mouse and Drosophila genomes is associated with a significant co-localization of several specific repetitive elements, notably many elements of the SINE family. These repeats tend to be the oldest ones and are enriched in transcription factor binding sites. We propose that the co-localization of these repetitive elements may explain the global conservation of genome folding observed between homologous regions of the human and mouse genome. Taken together, these results support a contribution of specific repetitive elements in maintaining and/or reshaping genome architecture over evolutionary times.}, } @article {pmid26598941, year = {2015}, author = {Gibbons, SM and Gilbert, JA}, title = {Microbial diversity--exploration of natural ecosystems and microbiomes.}, journal = {Current opinion in genetics & development}, volume = {35}, number = {}, pages = {66-72}, pmid = {26598941}, issn = {1879-0380}, support = {T32 EB009412/EB/NIBIB NIH HHS/United States ; 5T-32EB-009412/EB/NIBIB NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; *Biodiversity ; Environment ; Genetic Variation/*genetics ; Microbiota/*genetics ; }, abstract = {Microorganisms are the pillars of life on Earth. Over billions of years, they have evolved into every conceivable niche on the planet. Microbes reshaped the oceans and atmosphere and gave rise to conditions conducive to multicellular organisms. Only in the past decade have we started to peer deeply into the microbial cosmos, and what we have found is amazing. Microbial ecosystems behave, in many ways, like large-scale ecosystems, although there are important exceptions. We review recent advances in our understanding of how microbial diversity is distributed across environments, how microbes influence the ecosystems in which they live, and how these nano-machines might be harnessed to advance our understanding of the natural world.}, } @article {pmid26596625, year = {2015}, author = {Borowiec, ML and Lee, EK and Chiu, JC and Plachetzki, DC}, title = {Extracting phylogenetic signal and accounting for bias in whole-genome data sets supports the Ctenophora as sister to remaining Metazoa.}, journal = {BMC genomics}, volume = {16}, number = {}, pages = {987}, pmid = {26596625}, issn = {1471-2164}, mesh = {Animals ; Bias ; Ctenophora/*genetics ; *Data Mining ; Evolution, Molecular ; Genetic Loci/genetics ; *Genomics ; Humans ; *Phylogeny ; }, abstract = {BACKGROUND: Understanding the phylogenetic relationships among major lineages of multicellular animals (the Metazoa) is a prerequisite for studying the evolution of complex traits such as nervous systems, muscle tissue, or sensory organs. Transcriptome-based phylogenies have dramatically improved our understanding of metazoan relationships in recent years, although several important questions remain. The branching order near the base of the tree, in particular the placement of the poriferan (sponges, phylum Porifera) and ctenophore (comb jellies, phylum Ctenophora) lineages is one outstanding issue. Recent analyses have suggested that the comb jellies are sister to all remaining metazoan phyla including sponges. This finding is surprising because it suggests that neurons and other complex traits, present in ctenophores and eumetazoans but absent in sponges or placozoans, either evolved twice in Metazoa or were independently, secondarily lost in the lineages leading to sponges and placozoans.

RESULTS: To address the question of basal metazoan relationships we assembled a novel dataset comprised of 1080 orthologous loci derived from 36 publicly available genomes representing major lineages of animals. From this large dataset we procured an optimized set of partitions with high phylogenetic signal for resolving metazoan relationships. This optimized data set is amenable to the most appropriate and computationally intensive analyses using site-heterogeneous models of sequence evolution. We also employed several strategies to examine the potential for long-branch attraction to bias our inferences. Our analyses strongly support the Ctenophora as the sister lineage to other Metazoa. We find no support for the traditional view uniting the ctenophores and Cnidaria. Our findings are supported by Bayesian comparisons of topological hypotheses and we find no evidence that they are biased by long-branch attraction.

CONCLUSIONS: Our study further clarifies relationships among early branching metazoan lineages. Our phylogeny supports the still-controversial position of ctenophores as sister group to all other metazoans. This study also provides a workflow and computational tools for minimizing systematic bias in genome-based phylogenetic analyses. Future studies of metazoan phylogeny will benefit from ongoing efforts to sequence the genomes of additional invertebrate taxa that will continue to inform our view of the relationships among the major lineages of animals.}, } @article {pmid26594222, year = {2015}, author = {Plackett, AR and Di Stilio, VS and Langdale, JA}, title = {Ferns: the missing link in shoot evolution and development.}, journal = {Frontiers in plant science}, volume = {6}, number = {}, pages = {972}, pmid = {26594222}, issn = {1664-462X}, support = {BB/C513069/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Shoot development in land plants is a remarkably complex process that gives rise to an extreme diversity of forms. Our current understanding of shoot developmental mechanisms comes almost entirely from studies of angiosperms (flowering plants), the most recently diverged plant lineage. Shoot development in angiosperms is based around a layered multicellular apical meristem that produces lateral organs and/or secondary meristems from populations of founder cells at its periphery. In contrast, non-seed plant shoots develop from either single apical initials or from a small population of morphologically distinct apical cells. Although developmental and molecular information is becoming available for non-flowering plants, such as the model moss Physcomitrella patens, making valid comparisons between highly divergent lineages is extremely challenging. As sister group to the seed plants, the monilophytes (ferns and relatives) represent an excellent phylogenetic midpoint of comparison for unlocking the evolution of shoot developmental mechanisms, and recent technical advances have finally made transgenic analysis possible in the emerging model fern Ceratopteris richardii. This review compares and contrasts our current understanding of shoot development in different land plant lineages with the aim of highlighting the potential role that the fern C. richardii could play in shedding light on the evolution of underlying genetic regulatory mechanisms.}, } @article {pmid26583681, year = {2016}, author = {Chen, J and Xie, ZR and Wu, Y}, title = {Elucidating the general principles of cell adhesion with a coarse-grained simulation model.}, journal = {Molecular bioSystems}, volume = {12}, number = {1}, pages = {205-218}, doi = {10.1039/c5mb00612k}, pmid = {26583681}, issn = {1742-2051}, mesh = {Cell Adhesion/*physiology ; Cell Adhesion Molecules ; Cell Membrane/genetics/metabolism ; *Computer Simulation ; Membrane Proteins/metabolism ; *Models, Biological ; Models, Statistical ; Monte Carlo Method ; Protein Binding ; Signal Transduction ; Thermodynamics ; }, abstract = {Cell adhesion plays an indispensable role in coordinating physiological functions in multicellular organisms. During this process, specific types of cell adhesion molecules interact with each other from the opposite sides of neighboring cells. Following this trans-interaction, many cell adhesion molecules further aggregate into clusters through cis interactions. Beyond the molecule level, adhesion can be affected by multiple cellular factors due to the complexity of membrane microenvironments, including its interplay with cell signaling. However, despite tremendous advances in experimental developments, little is understood about the general principles of cell adhesion and its functional impacts. Here a mesoscopic simulation method is developed to tackle this problem. We illustrated that specific spatial patterns of membrane protein clustering are originated from different geometrical arrangements of their binding interfaces, while the size of clusters is closely regulated by molecular flexibility. Different scenarios of cooperation between trans and cis interactions of cell adhesion molecules were further tested. Additionally, impacts of membrane environments on cell adhesion were evaluated, such as the presence of a cytoskeletal meshwork, the membrane tension and the size effect of different membrane proteins on cell surfaces. Finally, by simultaneously simulating adhesion and oligomerization of signaling receptors, we found that the interplay between these two systems can be either positive or negative, closely depending on the spatial and temporal patterns of their molecular interactions. Therefore, our computational model pave the way for understanding the molecular mechanisms of cell adhesion and its biological functions in regulating cell signaling pathways.}, } @article {pmid26575626, year = {2015}, author = {Lynch, M and Marinov, GK}, title = {The bioenergetic costs of a gene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {51}, pages = {15690-15695}, pmid = {26575626}, issn = {1091-6490}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; R01-GM036827/GM/NIGMS NIH HHS/United States ; }, mesh = {*Energy Metabolism ; *Evolution, Molecular ; Genetic Drift ; Selection, Genetic ; }, abstract = {An enduring mystery of evolutionary genomics concerns the mechanisms responsible for lineage-specific expansions of genome size in eukaryotes, especially in multicellular species. One idea is that all excess DNA is mutationally hazardous, but weakly enough so that genome-size expansion passively emerges in species experiencing relatively low efficiency of selection owing to small effective population sizes. Another idea is that substantial gene additions were impossible without the energetic boost provided by the colonizing mitochondrion in the eukaryotic lineage. Contrary to this latter view, analysis of cellular energetics and genomics data from a wide variety of species indicates that, relative to the lifetime ATP requirements of a cell, the costs of a gene at the DNA, RNA, and protein levels decline with cell volume in both bacteria and eukaryotes. Moreover, these costs are usually sufficiently large to be perceived by natural selection in bacterial populations, but not in eukaryotes experiencing high levels of random genetic drift. Thus, for scaling reasons that are not yet understood, by virtue of their large size alone, eukaryotic cells are subject to a broader set of opportunities for the colonization of novel genes manifesting weakly advantageous or even transiently disadvantageous phenotypic effects. These results indicate that the origin of the mitochondrion was not a prerequisite for genome-size expansion.}, } @article {pmid30151141, year = {2015}, author = {Wang, L and Wu, N and Zhu, Y and Song, W and Zhao, X and Li, Y and Hu, Y}, title = {The divergence and positive selection of the plant-specific BURP-containing protein family.}, journal = {Ecology and evolution}, volume = {5}, number = {22}, pages = {5394-5412}, pmid = {30151141}, issn = {2045-7758}, abstract = {BURP domain-containing proteins belong to a plant-specific protein family and have diverse roles in plant development and stress responses. However, our understanding about the genetic divergence patterns and evolutionary rates of these proteins remain inadequate. In this study, 15 plant genomes were explored to elucidate the genetic origins, divergence, and functions of these proteins. One hundred and twenty-five BURP protein-encoding genes were identified from four main plant lineages, including 13 higher plant species. The absence of BURP family genes in unicellular and multicellular algae suggests that this family (1) appeared when plants shifted from relatively stable aquatic environments to land, where conditions are more variable and stressful, and (2) is critical in the adaptation of plants to adverse environments. Promoter analysis revealed that several responsive elements to plant hormones and external environment stresses are concentrated in the promoter region of BURP protein-encoding genes. This finding confirms that these genes influence plant stress responses. Several segmentally and tandem-duplicated gene pairs were identified from eight plant species. Thus, in general, BURP domain-containing genes have been subject to strong positive selection, even though these genes have conformed to different expansion models in different species. Our study also detected certain critical amino acid sites that may have contributed to functional divergence among groups or subgroups. Unexpectedly, all of the critical amino acid residues of functional divergence and positive selection were exclusively located in the C-terminal region of the BURP domain. In conclusion, our results contribute novel insights into the genetic divergence patterns and evolutionary rates of BURP proteins.}, } @article {pmid27008743, year = {2015}, author = {Isakov, DV and Isakov, VA}, title = {[CYCLOFERON: MECHANISM OF ACTION, AND NEW PROSPECTS FOR APPLICATION IN CLINICAL PRACTICE].}, journal = {Klinicheskaia meditsina}, volume = {93}, number = {9}, pages = {46-51}, pmid = {27008743}, issn = {0023-2149}, mesh = {Acridines/*pharmacology ; Adaptive Immunity/*drug effects ; Animals ; Humans ; Infections/*drug therapy/immunology ; Interferon Inducers/pharmacology ; }, abstract = {Multicellular organisms exist in constant interaction with various species of microflora both at the body surface and in internal media. The mechanism of recognition of conservative molecular structures of infectious origin formed at the earliest stages of evolution before the appearance of the genes of the immunoglobulin superfamily in jawed vertebrates (Gnathostomata) that made up a basis for the development of clonal specificity of B- and T-lymphocytes as adaptive immunity factors. This paper considers the mechanism of action of cycloferon as an inductor of endogenous interferon synthesis and the new prospects for its application in clinical medicine.}, } @article {pmid26988326, year = {2014}, author = {Yamagishi, T and Müller, DG and Kawai, H}, title = {Comparative transcriptome analysis of Discosporangium mesarthrocarpum (Phaeophyceae), Schizocladia ischiensis (Schizocladiophyceae), and Phaeothamnion confervicola (Phaeothamniophyceae), with special reference to cell wall-related genes.}, journal = {Journal of phycology}, volume = {50}, number = {3}, pages = {543-551}, doi = {10.1111/jpy.12190}, pmid = {26988326}, issn = {1529-8817}, abstract = {Within the stramenopile lineage, only brown algae (Phaeophyceae) have evolved complex multicellularity, although some other members of the lineage (e.g., Schizocladia in Schizocladiophyceae; Phaeothamnion in Phaeothamniophyceae) also develop simple multicellular thalli. The development of an adherent extracellular matrix (ECM) is considered to be one of the key steps in the evolution of multicellularity, because ECM is involved in adhesion of cells to each other and in cell-cell communication essential for developmental, reproductive, and sophisticated defense systems. Because there are no unicellular organisms within brown algae, we considered that comparison of other stramenopile taxa closely related to brown algae and having multicellular thalli could yield clues to elucidate the evolution of multicellularity in brown algae. In this study, we investigated transcriptomes involved in cell wall polysaccharide metabolism of three stramenopile species, Discosporangium mesarthrocarpum, which is suggested to be one of the most basal taxa within Phaeophyceae, S. ischiensis, and P. confervicola. We employed 454-FLX high-throughput pyrosequencing to generate expressed sequence tag (EST) databases for these species, and performed comparative analyses between these databases and the genome sequence of the brown alga Ectocarpus siliculosus. Results indicate that cell wall polysaccharide metabolism pathways of D. mesarthrocarpum are similar to E. siliculosus, whereas those of S. ischiensis and P. confervicola are significantly different from E. siliculosus, suggesting that the components of the cell wall in S. ischiensis and P. confervicola are likely to be different from those of E. siliculosus.}, } @article {pmid31354387, year = {2014}, author = {Herron, MD and Ghimire, S and Vinikoor, CR and Michod, RE}, title = {Fitness trade-offs and developmental constraints in the evolution of soma: an experimental study in a volvocine alga.}, journal = {Evolutionary ecology research}, volume = {16}, number = {3}, pages = {203-221}, pmid = {31354387}, issn = {1522-0613}, support = {NNA17BB05A//Intramural NASA/United States ; }, abstract = {BACKGROUND: The evolution of mortal somatic cells was a critical step in the evolution of complex body plans and the major radiations of multicellular life. In the volvocine green algae, somatic cells are hypothesized to mitigate an increasing cost of reproduction as colony size increases, primarily by providing motility to the colony during reproduction.

QUESTIONS: Does selection on colony size cause an evolutionary response in proportion of somatic cells? Does the effect of selection on colony size differ in environments that differ in the importance of motility?

METHODS: We subjected an outcrossed population of the volvocine alga Pleodorina starrii to selection on colony size in still and mixed environments. After approximately 40 generations with periodic selection, we estimated the relationship between colony size and proportion of soma in evolved colonies from both environments.

RESULTS: In the largest size category, colonies selected in the still environment (in which motility is hypothesized to be more important) had a higher proportion of soma than those from the mixed environment. Within-strain variation in cell number was surprisingly large: up to 16-fold for some genotypes. The positive among-species relationship between colony size and proportion of soma was paralleled within the larger (16- to 64-celled) colonies of P. starrii, but not within the smaller (4- and 8-celled) colonies, which had the highest proportions of soma, suggesting the existence of an evolutionary constraint preventing optimization of soma in the smallest size classes.}, } @article {pmid27007308, year = {2013}, author = {Farnham, G and Strittmatter, M and Coelho, S and Cock, JM and Brownlee, C}, title = {Gene silencing in Fucus embryos: developmental consequences of RNAi-mediated cytoskeletal disruption.}, journal = {Journal of phycology}, volume = {49}, number = {5}, pages = {819-829}, doi = {10.1111/jpy.12096}, pmid = {27007308}, issn = {0022-3646}, support = {P18266/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; REI20579/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Brown algae (Phaeophyceae) are an important algal class that play a range of key ecological roles. They are often important components of rocky shore communities. A number of members of the Fucales and Ectocarpales have provided models for the study of multicellular evolution, reproductive biology and polarized development. Indeed the fucoid algae exhibit the unusual feature of inducible embryo polarization, allowing many classical studies of polarity induction. The potential of further studies of brown algae in these important areas has been increasingly hindered by the absence of tools for manipulation of gene expression that would facilitate further mechanistic analysis and gene function studies at a molecular level. The aim of this study was to establish a method that would allow the analysis of gene function through RNAi-mediated gene knockdown. We show that injection of double-stranded RNA (dsRNA) corresponding to an α-tubulin gene into Fucus serratus Linnaeus zygotes induces the loss of a large proportion of the microtubule cytoskeleton, leading to growth arrest and disruption of cell division. Injection of dsRNA targeting β-actin led to reduced rhizoid growth, enlarged cells and the failure to develop apical hair cells. The silencing effect on actin expression was maintained for 3 months. These results indicate that the Fucus embryo possesses a functional RNA interference system that can be exploited to investigate gene function during embryogenesis.}, } @article {pmid29354666, year = {2013}, author = {Blaisdell, AP and Pottenger, BC and Torday, JS}, title = {From heart beats to health recipes: The role of fractal physiology in the Ancestral Health movement.}, journal = {Journal of evolution and health}, volume = {1}, number = {1}, pages = {}, pmid = {29354666}, issn = {2334-3591}, support = {R01 HL055268/HL/NHLBI NIH HHS/United States ; R01 NS059076/NS/NINDS NIH HHS/United States ; }, abstract = {The human body-an amazing biological system that scales up fractally from its cellular building blocks-exhibits an incredible ability to self heal. Why then, are chronic diseases and degeneration on the rise in the population? Why are we sicker, more obese, and more depressed and stressed than ever before in human history? Why can't we heal? The answers to these questions may lie in our ancestry, and modern departure from the human ecological niche. The ability to heal requires proper spatio-temporal inputs-nutrition, sleep, stress, activity, and socialization-in order for cellular signaling to occur properly across semi-permeable cell membranes. We first review key steps in the evolutionary history of multicellular life, focusing on the fundamental role of cell-cell interactions. Next, we present this as an important framework by which to understand how the entrainment of physiological signals in homeostatic mechanisms reveals new insights into the processes of disease. Examples are drawn from the evolution of metabolism, nutrition, and respiration in multicellular life. We argue that disease processes result from a mismatch between the physiological inputs an individual receives and their optimal amount and fractal distribution as determined by an individual's ancestry. A comparative analysis is a useful tool by which to illuminate deep homologies that reveal a mechanistic account for disease processes. This cell-molecular approach provides a useful contrast to the traditional reductionist approach to disease exemplified by the human genome project. As an example, we describe how cell-cell communication drives the ontogeny and phylogeny of physiology, producing the tissues, organs, and organ systems that hierarchically serve human physiology on various levels. Modern society, with its disconnected and stress-riddled lifestyle, is increasingly failing to provide the proper inputs for healthy gene expression and physiological function. Thus, the answers to our modern health woes-physical, mental, and social-may lie in acknowledging the powerful roles that our past has played in shaping our bodies. Finding ways to provide the proper inputs of the human ecological niche in the modern day may lead to significant, perhaps staggering improvements in our health and wellness. The fractal mathematics underpinning these dynamics also serves as a metaphor for the Ancestral Health Movement, which is currently arising as a multi-cultural, multi-national grass-roots pluralistic phenomenon.}, } @article {pmid27008999, year = {2012}, author = {Stiller, JW and Perry, J and Rymarquis, LA and Accerbi, M and Green, PJ and Prochnik, S and Lindquist, E and Chan, CX and Yarish, C and Lin, S and Zhuang, Y and Blouin, NA and Brawley, SH}, title = {MAJOR DEVELOPMENTAL REGULATORS AND THEIR EXPRESSION IN TWO CLOSELY RELATED SPECIES OF PORPHYRA (RHODOPHYTA)(1).}, journal = {Journal of phycology}, volume = {48}, number = {4}, pages = {883-896}, doi = {10.1111/j.1529-8817.2012.01138.x}, pmid = {27008999}, issn = {0022-3646}, abstract = {Little is known about the genetic and biochemical mechanisms that underlie red algal development, for example, why the group failed to evolve complex parenchyma and tissue differentiation. Here we examined expressed sequence tag (EST) data from two closely related species, Porphyra umbilicalis (L.) J. Agardh and P. purpurea (Roth) C. Agardh, for conserved developmental regulators known from model eukaryotes, and their expression levels in several developmental stages. Genes for most major developmental families were present, including MADS-box and homeodomain (HD) proteins, SNF2 chromatin-remodelers, and proteins involved in sRNA biogenesis. Some of these genes displayed altered expression correlating with different life history stages or cell types. Notably, two ESTs encoding HD proteins showed eightfold higher expression in the P. purpurea sporophyte (conchocelis) than in the gametophyte (blade), whereas two MADS domain-containing paralogs showed significantly different patterns of expression in the conchocelis and blade respectively. These developmental gene families do not appear to have undergone the kinds of dramatic expansions in copy number found in multicellular land plants and animals, which are important for regulating developmental processes in those groups. Analyses of small RNAs did not validate the presence of miRNAs, but homologs of Argonaute were present. In general, it appears that red algae began with a similar molecular toolkit for directing development as did other multicellular eukaryotes, but probably evolved altered roles for many key proteins, as well as novel mechanisms yet to be discovered.}, } @article {pmid27021987, year = {2011}, author = {Solari, CA and Drescher, K and Goldstein, RE}, title = {THE FLAGELLAR PHOTORESPONSE IN VOLVOX SPECIES (VOLVOCACEAE, CHLOROPHYCEAE)[1].}, journal = {Journal of phycology}, volume = {47}, number = {3}, pages = {580-583}, doi = {10.1111/j.1529-8817.2011.00983.x}, pmid = {27021987}, issn = {1529-8817}, support = {BB/F021844/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Steering their swimming direction toward the light is crucial for the viability of Volvox colonies, the larger members of the volvocine algae. While it is known that this phototactic steering is achieved by a difference in behavior of the flagella on the illuminated and shaded sides, conflicting reports suggest that this asymmetry arises either from a change in beating direction or a change in beating frequency. Here, we report direct observations of the flagellar behavior of various Volvox species with different phyletic origin in response to light intensity changes and thereby resolve this controversy: Volvox barberi W. Shaw from the section Volvox sensu Nozaki (2003) changes the direction of the flagellar beating plane, while species encompassed in the group Eudorina (Volvox carteri F. Stein, Volvox aureus Ehrenb., and Volvox tertius Art. Mey.) decrease the flagellar beating frequency, sometimes down to flagellar arrest.}, } @article {pmid29542160, year = {2000}, author = {McCourt, RM and Karol, KG and Bell, J and Helm-Bychowski, KM and Grajewska, A and Wojciechowski, MF and Hoshaw, RW}, title = {PHYLOGENY OF THE CONJUGATING GREEN ALGAE (ZYGNEMOPHYCEAE) BASED ON rbc L SEQUENCES.}, journal = {Journal of phycology}, volume = {36}, number = {4}, pages = {747-758}, doi = {10.1046/j.1529-8817.2000.99106.x}, pmid = {29542160}, issn = {1529-8817}, abstract = {Sequences of the gene encoding the large subunit of RUBISCO (rbcL) for 30 genera in the six currently recognized families of conjugating green algae (Desmidiaceae, Gonatozygaceae, Mesotaeniaceae, Peniaceae, and Zygnemataceae) were analyzed using maximum parsimony and maximum likelihood; bootstrap replications were performed as a measure of support for clades. Other Charophyceae sensu Mattox and Stewart and representative land plants were used as outgroups. All analyses supported the monophyly of the conjugating green algae. The Desmidiales, or placoderm desmids, constitute a monophyletic group, with moderate to strong support for the four component families of this assemblage (Closteriaceae, Desmidiaceae, Gonatozygaceae, and Peniaceae). The analyses showed that the two families of Zygnematales (Mesotaeniaceae, Zygnemataceae), which have plesiomorphic, unornamented and unsegmented cell walls, are not monophyletic. However, combined taxa of these two traditional families may constitute a monophyletic group. Partitioning the data by codon position revealed no significant differences across all positions or between partitions of positions one and two versus position three. The trees resulting from parsimony analyses using first plus second positions versus third position differed only in topology of branches with poor bootstrap support. The tree derived from third positions only was more resolved than the tree derived from first and second positions. The rbcL-based phylogeny is largely congruent with published analyses of small subunit rDNA sequences for the Zygnematales. The molecular data do not support hypotheses of monophyly for groups of extant unicellular and filamentous or colonial desmid genera exhibiting a common cell shape. A trend is evident from simple omniradiate cell shapes to taxa with lobed cell and plastid shapes, which supports the hypothesis that chloroplast shape evolved generally from simple to complex. The data imply that multicellular placoderm desmids are monophyletic. Several anomalous placements of genera were found, including the saccoderm desmid Roya in the Gonatozygaceae and the zygnematacean Entransia in the Coleochaetales. The former is strongly supported, although the latter is not, and Entransia's phylogenetic position warrants further study.}, } @article {pmid28565284, year = {1996}, author = {Wagner, A}, title = {DOES EVOLUTIONARY PLASTICITY EVOLVE?.}, journal = {Evolution; international journal of organic evolution}, volume = {50}, number = {3}, pages = {1008-1023}, doi = {10.1111/j.1558-5646.1996.tb02342.x}, pmid = {28565284}, issn = {1558-5646}, abstract = {During the development of a multicellular organism from a zygote, a large number of epigenetic interactions take place on every level of suborganismal organization. This raises the possibility that the system of epigenetic interactions may compensate or "buffer" some of the changes that occur as mutations on its lowest levels, and thus stabilize the phenotype with respect to mutations. This hypothetical phenomenon will be called "epigenetic stability." Its potential importance stems from the fact that phenotypic variation with a genetic basis is an essential prerequisite for evolution. Thus, variation in epigenetic stability might profoundly affect attainable rates of evolution. While representing a systemic property of a developmental system, epigenetic stability might itself be genetically determined and thus be subject to evolutionary change. Whether or not this is the case should ideally be answered directly, that is, by experimentation. The time scale involved and our insufficient quantitative understanding of developmental pathways will probably preclude such an approach in the foreseeable future. Preliminary answers are sought here by using a biochemically motivated model of a small but central part of a developmental pathway. Modeled are sets of transcriptional regulators that mutually regulate each other's expression and thereby form stable gene expression patterns. Such gene-expression patterns, crucially involved in determining developmental pattern formation events, are most likely subject to strong stabilizing natural selection. After long periods of stabilizing selection, the fraction of mutations causing changes in gene-expression patterns is substantially reduced in the model. Epigenetic stability has increased. This phenomenon is found for widely varying regulatory scenarios among transcription factor genes. It is discussed that only epistatic (nonlinear) gene interactions can cause such change in epigenetic stability. Evidence from paleontology, molecular evolution, development, and genetics, consistent with the existence of variation in epigenetic stability, is discussed. The relation of epigenetic stability to developmental canalization is outlined. Experimental scenarios are suggested that may provide further evidence.}, } @article {pmid28564863, year = {1995}, author = {Blackstone, NW}, title = {PERSPECTIVE A UNITS-OF-EVOLUTION PERSPECTIVE ON THE ENDOSYMBIONT THEORY OF THE ORIGIN OF THE MITOCHONDRION.}, journal = {Evolution; international journal of organic evolution}, volume = {49}, number = {5}, pages = {785-796}, doi = {10.1111/j.1558-5646.1995.tb02315.x}, pmid = {28564863}, issn = {1558-5646}, abstract = {Discussions of mitochondria and their hosts often conceptualize this relationship in a more or less modern form, focusing on the metabolic benefits of mitochondria to the host cell or on the possibility of intragenomic conflict. A more inclusive units-of-evolution perspective recognizes that both costs and benefits must be viewed from the level of the cells that initiated this interaction, the protomitochondrion and the primitive host cell. From this perspective, ecological and physiological considerations become central to the characterization of initial and subsequent host-mitochondria associations. Foremost among these considerations is the generation of superoxide radicals by modern mitochondria and the deleterious effects of these endogenous oxidants on modern eukaryotic cells. Because of their photosynthetic and aerobic ecologies, protomitochondria likely were relatively tolerant of such oxidants; anaerobic, heterotrophic, primitive host cells, on the other hand, likely were not. In the initial association of host and symbiont, the latter may have manipulated the former's life history by means of both endogenous oxidants and a superabundance of ATP. A resolution of this units-of-evolution conflict was necessary to continue this association, and this resolution, in a ritualized form, may have shaped the evolution of many features of modern eukaryotic cells and mitochondria, for example, the messenger functions of calcium ions, the regulatory role of phosphorylation cascades in cell-division cycles, the absence from the mitochondrial genome of replication factors, transcription factors, and adenine nucleotide carrier genes. The initial host-mitochondria interaction may have further channeled the evolution of multicellular eukaryotes, particularly animals, resulting in the association of mitochondria and the germinal plasm and in the use of extracellular ATP and endogenous oxidants as developmental signals. Evolutionary explanations for "free-radical" theories of development and aging are thus suggested.}, } @article {pmid28564887, year = {1993}, author = {Avise, JC}, title = {PERSPECTIVE: THE EVOLUTIONARY BIOLOGY OF AGING, SEXUAL REPRODUCTION, AND DNA REPAIR.}, journal = {Evolution; international journal of organic evolution}, volume = {47}, number = {5}, pages = {1293-1301}, doi = {10.1111/j.1558-5646.1993.tb02155.x}, pmid = {28564887}, issn = {1558-5646}, abstract = {Three recent books on the evolutionary biology of aging and sexual reproduction are reviewed, with particular attention focused on the provocative suggestion by Bernstein and Bernstein (1991) that senescence and genetic recombination are related epiphenomena stemming from the universal challenge to life posed by DNA damages and the need for damage repair. Embellishments to these theories on aging and sex are presented that consider two relevant topics neglected or underemphasized in the previous treatments. The first concerns discussion of cytoplasmic genomes (such as mtDNA), which are transmitted asexually and therefore do not abide by the recombinational rules of nuclear genomes; the second considers the varying degrees of cellular and molecular autonomy which distinguish unicellular from multicellular organisms, germ cells from somatic cells, and sexual from asexual genomes. Building on the Bernsteins' suggestions, two routes to immortality for cell lineages appear to be available to life: an asexual strategy (exemplified by some bacteria), whereby cell proliferation outpaces the accumulation of DNA damages, thereby circumventing Muller's ratchet; and a sexual strategy (exemplified by germlines in multicellular organisms), whereby recombinational repair of DNA damages in conjunction with cell proliferation and gametic selection counter the accumulation of nuclear DNA damages. If true, then elements of both the recombinational strategy (nuclear DNA) and replacement strategy (cytoplasmic DNA) may operate simultaneously in the germ-cell lineages of higher organisms, producing at least some gametes that are purged of the DNA damages accumulated during the lifetime of the somatic parent. For multicellular organisms, production of functionally autonomous and genetically screened gametic cells is a necessary and sufficient condition for the continuance of life.}, } @article {pmid28568082, year = {1993}, author = {Morris, PJ}, title = {THE DEVELOPMENTAL ROLE OF THE EXTRACELLULAR MATRIX SUGGESTS A MONOPHYLETIC ORIGIN OF THE KINGDOM ANIMALIA.}, journal = {Evolution; international journal of organic evolution}, volume = {47}, number = {1}, pages = {152-165}, doi = {10.1111/j.1558-5646.1993.tb01206.x}, pmid = {28568082}, issn = {1558-5646}, abstract = {The fundamental events of early development are similar in all animals, including sponges. Recent developments in the molecular biology of the extracellular matrix strongly suggest that the molecular mechanisms behind these events are also similar among all animals. I propose that the complex (collagen, proteoglycan, adhesive glycoprotein, and integrin) system that mediates cell motility and transitions between epithelial and motile cell types is central to multicellularity in animals. I further propose that the extracellular matrix is a deep rooted homology that unites the kingdom Animalia into a monophyletic group of multicellular organisms.}, } @article {pmid26573836, year = {2015}, author = {Yuan, S and Zheng, T and Li, P and Yang, R and Ruan, J and Huang, S and Wu, Z and Xu, A}, title = {Characterization of Amphioxus IFN Regulatory Factor Family Reveals an Archaic Signaling Framework for Innate Immune Response.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {195}, number = {12}, pages = {5657-5666}, doi = {10.4049/jimmunol.1501927}, pmid = {26573836}, issn = {1550-6606}, mesh = {Amino Acid Sequence ; Animals ; Biological Evolution ; Humans ; Immunity, Innate ; Interferon Regulatory Factor-1/genetics/*metabolism ; Interferon Regulatory Factors/genetics/*metabolism ; *Lancelets ; Molecular Sequence Data ; Protein Structure, Tertiary/genetics ; Sequence Homology, Amino Acid ; Species Specificity ; }, abstract = {The IFN regulatory factor (IRF) family encodes transcription factors that play important roles in immune defense, stress response, reproduction, development, and carcinogenesis. Although the origin of the IRF family has been dated back to multicellular organisms, invertebrate IRFs differ from vertebrate IRFs in genomic structure and gene synteny, and little is known about their functions. Through comparison of multiple amphioxus genomes, in this study we suggested that amphioxus contains nine IRF members, whose orthologs are supposed to be shared among three amphioxus species. As the orthologs to the vertebrate IRF1 and IRF4 subgroups, Branchiostoma belcheri tsingtauense (bbt)IRF1 and bbtIRF8 bind the IFN-stimulated response element (ISRE) and were upregulated when amphioxus intestinal cells were stimulated with poly(I:C). As amphioxus-specific IRFs, both bbtIRF3 and bbtIRF7 bind ISRE. When activated, they can be phosphorylated by bbtTBK1 and then translocate into nucleus for target gene transcription. As transcriptional repressors, bbtIRF2 and bbtIRF4 can inhibit the transcriptional activities of bbtIRF1, 3, 7, and 8 by competing for the binding of ISRE. Interestingly, amphioxus IRF2, IRF8, and Rel were identified as target genes of bbtIRF1, bbtIRF7, and bbtIRF3, respectively, suggesting a dynamic feedback regulation among amphioxus IRF and NF-κB. Collectively, to our knowledge we present for the first time an archaic IRF signaling framework in a basal chordate, shedding new insights into the origin and evolution of vertebrate IFN-based antiviral networks.}, } @article {pmid26569502, year = {2015}, author = {Amano, R and Nakayama, H and Morohoshi, Y and Kawakatsu, Y and Ferjani, A and Kimura, S}, title = {A Decrease in Ambient Temperature Induces Post-Mitotic Enlargement of Palisade Cells in North American Lake Cress.}, journal = {PloS one}, volume = {10}, number = {11}, pages = {e0141247}, pmid = {26569502}, issn = {1932-6203}, mesh = {Arabidopsis/cytology/genetics/*growth & development ; Cell Communication ; Cell Cycle ; Cell Proliferation ; *Cell Size ; Environment ; Gene Expression Regulation, Plant ; *Mitosis ; Phenotype ; Phylogeny ; Plant Leaves/cytology ; Plant Physiological Phenomena ; Rorippa/cytology/genetics/*growth & development ; Species Specificity ; *Temperature ; }, abstract = {In order to maintain organs and structures at their appropriate sizes, multicellular organisms orchestrate cell proliferation and post-mitotic cell expansion during morphogenesis. Recent studies using Arabidopsis leaves have shown that compensation, which is defined as post-mitotic cell expansion induced by a decrease in the number of cells during lateral organ development, is one example of such orchestration. Some of the basic molecular mechanisms underlying compensation have been revealed by genetic and chimeric analyses. However, to date, compensation had been observed only in mutants, transgenics, and γ-ray-treated plants, and it was unclear whether it occurs in plants under natural conditions. Here, we illustrate that a shift in ambient temperature could induce compensation in Rorippa aquatica (Brassicaceae), a semi-aquatic plant found in North America. The results suggest that compensation is a universal phenomenon among angiosperms and that the mechanism underlying compensation is shared, in part, between Arabidopsis and R. aquatica.}, } @article {pmid26560631, year = {2015}, author = {Cayrou, C and Ballester, B and Peiffer, I and Fenouil, R and Coulombe, P and Andrau, JC and van Helden, J and Méchali, M}, title = {The chromatin environment shapes DNA replication origin organization and defines origin classes.}, journal = {Genome research}, volume = {25}, number = {12}, pages = {1873-1885}, pmid = {26560631}, issn = {1549-5469}, mesh = {Animals ; Base Composition ; Chromatin/*genetics/*metabolism ; Chromatin Assembly and Disassembly ; Chromosome Mapping ; Cluster Analysis ; Computational Biology/methods ; *DNA Replication ; Embryonic Stem Cells ; Genome ; Genomics ; Heterochromatin/genetics/metabolism ; High-Throughput Nucleotide Sequencing ; Histones ; Humans ; Mice ; Nucleosomes/genetics/metabolism ; Nucleotide Motifs ; Origin Recognition Complex ; *Replication Origin ; Transcriptional Activation ; }, abstract = {To unveil the still-elusive nature of metazoan replication origins, we identified them genome-wide and at unprecedented high-resolution in mouse ES cells. This allowed initiation sites (IS) and initiation zones (IZ) to be differentiated. We then characterized their genetic signatures and organization and integrated these data with 43 chromatin marks and factors. Our results reveal that replication origins can be grouped into three main classes with distinct organization, chromatin environment, and sequence motifs. Class 1 contains relatively isolated, low-efficiency origins that are poor in epigenetic marks and are enriched in an asymmetric AC repeat at the initiation site. Late origins are mainly found in this class. Class 2 origins are particularly rich in enhancer elements. Class 3 origins are the most efficient and are associated with open chromatin and polycomb protein-enriched regions. The presence of Origin G-rich Repeated elements (OGRE) potentially forming G-quadruplexes (G4) was confirmed at most origins. These coincide with nucleosome-depleted regions located upstream of the initiation sites, which are associated with a labile nucleosome containing H3K64ac. These data demonstrate that specific chromatin landscapes and combinations of specific signatures regulate origin localization. They explain the frequently observed links between DNA replication and transcription. They also emphasize the plasticity of metazoan replication origins and suggest that in multicellular eukaryotes, the combination of distinct genetic features and chromatin configurations act in synergy to define and adapt the origin profile.}, } @article {pmid26554049, year = {2015}, author = {Jékely, G and Keijzer, F and Godfrey-Smith, P}, title = {An option space for early neural evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {370}, number = {1684}, pages = {}, pmid = {26554049}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Motor Activity ; Nervous System/*anatomy & histology ; *Nervous System Physiological Phenomena ; }, abstract = {The origin of nervous systems has traditionally been discussed within two conceptual frameworks. Input-output models stress the sensory-motor aspects of nervous systems, while internal coordination models emphasize the role of nervous systems in coordinating multicellular activity, especially muscle-based motility. Here we consider both frameworks and apply them to describe aspects of each of three main groups of phenomena that nervous systems control: behaviour, physiology and development. We argue that both frameworks and all three aspects of nervous system function need to be considered for a comprehensive discussion of nervous system origins. This broad mapping of the option space enables an overview of the many influences and constraints that may have played a role in the evolution of the first nervous systems.}, } @article {pmid26545090, year = {2015}, author = {Voordeckers, K and Kominek, J and Das, A and Espinosa-Cantú, A and De Maeyer, D and Arslan, A and Van Pee, M and van der Zande, E and Meert, W and Yang, Y and Zhu, B and Marchal, K and DeLuna, A and Van Noort, V and Jelier, R and Verstrepen, KJ}, title = {Adaptation to High Ethanol Reveals Complex Evolutionary Pathways.}, journal = {PLoS genetics}, volume = {11}, number = {11}, pages = {e1005635}, pmid = {26545090}, issn = {1553-7404}, mesh = {*Adaptation, Physiological ; Aneuploidy ; Ethanol/*pharmacology ; Haploidy ; }, abstract = {Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts.}, } @article {pmid26537913, year = {2015}, author = {Eyres, I and Boschetti, C and Crisp, A and Smith, TP and Fontaneto, D and Tunnacliffe, A and Barraclough, TG}, title = {Horizontal gene transfer in bdelloid rotifers is ancient, ongoing and more frequent in species from desiccating habitats.}, journal = {BMC biology}, volume = {13}, number = {}, pages = {90}, pmid = {26537913}, issn = {1741-7007}, support = {233232/ERC_/European Research Council/International ; BB/F020562/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/F020856/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Desiccation ; *Ecosystem ; *Gene Transfer, Horizontal ; Molecular Sequence Data ; Phylogeny ; Rotifera/*genetics ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {BACKGROUND: Although prevalent in prokaryotes, horizontal gene transfer (HGT) is rarer in multicellular eukaryotes. Bdelloid rotifers are microscopic animals that contain a higher proportion of horizontally transferred, non-metazoan genes in their genomes than typical of animals. It has been hypothesized that bdelloids incorporate foreign DNA when they repair their chromosomes following double-strand breaks caused by desiccation. HGT might thereby contribute to species divergence and adaptation, as in prokaryotes. If so, we expect that species should differ in their complement of foreign genes, rather than sharing the same set of foreign genes inherited from a common ancestor. Furthermore, there should be more foreign genes in species that desiccate more frequently. We tested these hypotheses by surveying HGT in four congeneric species of bdelloids from different habitats: two from permanent aquatic habitats and two from temporary aquatic habitats that desiccate regularly.

RESULTS: Transcriptomes of all four species contain many genes with a closer match to non-metazoan genes than to metazoan genes. Whole genome sequencing of one species confirmed the presence of these foreign genes in the genome. Nearly half of foreign genes are shared between all four species and an outgroup from another family, but many hundreds are unique to particular species, which indicates that HGT is ongoing. Using a dated phylogeny, we estimate an average of 12.8 gains versus 2.0 losses of foreign genes per million years. Consistent with the desiccation hypothesis, the level of HGT is higher in the species that experience regular desiccation events than those that do not. However, HGT still contributed hundreds of foreign genes to the species from permanently aquatic habitats. Foreign genes were mainly enzymes with various annotated functions that include catabolism of complex polysaccharides and stress responses. We found evidence of differential loss of ancestral foreign genes previously associated with desiccation protection in the two non-desiccating species.

CONCLUSIONS: Nearly half of foreign genes were acquired before the divergence of bdelloid families over 60 Mya. Nonetheless, HGT is ongoing in bdelloids and has contributed to putative functional differences among species. Variation among our study species is consistent with the hypothesis that desiccating habitats promote HGT.}, } @article {pmid26536128, year = {2015}, author = {Germer, J and Mann, K and Wörheide, G and Jackson, DJ}, title = {The Skeleton Forming Proteome of an Early Branching Metazoan: A Molecular Survey of the Biomineralization Components Employed by the Coralline Sponge Vaceletia Sp.}, journal = {PloS one}, volume = {10}, number = {11}, pages = {e0140100}, pmid = {26536128}, issn = {1932-6203}, mesh = {Animals ; Biological Evolution ; Calcification, Physiologic/physiology ; Calcium Carbonate/metabolism ; Carbonic Anhydrases/metabolism ; Chromatography, High Pressure Liquid ; Coccidioidin/classification/metabolism ; Extracellular Matrix Proteins/metabolism ; Mass Spectrometry ; Phylogeny ; Porifera/genetics/*metabolism ; Proteome/analysis/*metabolism ; Skeleton/metabolism ; Transcriptome ; }, abstract = {The ability to construct a mineralized skeleton was a major innovation for the Metazoa during their evolution in the late Precambrian/early Cambrian. Porifera (sponges) hold an informative position for efforts aimed at unraveling the origins of this ability because they are widely regarded to be the earliest branching metazoans, and are among the first multi-cellular animals to display the ability to biomineralize in the fossil record. Very few biomineralization associated proteins have been identified in sponges so far, with no transcriptome or proteome scale surveys yet available. In order to understand what genetic repertoire may have been present in the last common ancestor of the Metazoa (LCAM), and that may have contributed to the evolution of the ability to biocalcify, we have studied the skeletal proteome of the coralline demosponge Vaceletia sp. and compare this to other metazoan biomineralizing proteomes. We bring some spatial resolution to this analysis by dividing Vaceletia's aragonitic calcium carbonate skeleton into "head" and "stalk" regions. With our approach we were able to identify 40 proteins from both the head and stalk regions, with many of these sharing some similarity to previously identified gene products from other organisms. Among these proteins are known biomineralization compounds, such as carbonic anhydrase, spherulin, extracellular matrix proteins and very acidic proteins. This report provides the first proteome scale analysis of a calcified poriferan skeletal proteome, and its composition clearly demonstrates that the LCAM contributed several key enzymes and matrix proteins to its descendants that supported the metazoan ability to biocalcify. However, lineage specific evolution is also likely to have contributed significantly to the ability of disparate metazoan lineages to biocalcify.}, } @article {pmid26523091, year = {2015}, author = {Toyoshima, M and Aikawa, S and Yamagishi, T and Kondo, A and Kawai, H}, title = {A pilot-scale floating closed culture system for the multicellular cyanobacterium Arthrospira platensis NIES-39.}, journal = {Journal of applied phycology}, volume = {27}, number = {6}, pages = {2191-2202}, pmid = {26523091}, issn = {0921-8971}, abstract = {Microalgae are considered to be efficient bio-resources for biofuels and bio-based chemicals because they generally have high productivity. The filamentous cyanobacterium Arthrospira (Spirulina) platensis has been widely used for food, feed, and nutrient supplements and is usually cultivated in open ponds. In order to extend the surface area for growing this alga, we designed a pilot-scale floating closed culture system for cultivating A. platensis on open water and compared the growth and quality of the alga harvested at both subtropical and temperate regions. The biomass productivity of A. platensis NIES-39 was ca. 9 g dry biomass m[-2] day[-1] in summer at Awaji Island (warm temperature region) and ca. 10 and 6 g dry biomass m[-2] day[-1] in autumn and winter, respectively, at Ishigaki Island, (subtropical region) in Japan. If seawater can be used for culture media, culture cost can be reduced; therefore, we examined the influence of seawater salt concentrations on the growth of A. platensis NIES-39. Growth rates of A. platensis NIES-39 in diluted seawater with enrichment of 2.5 g L[-1] NaNO3, 0.01 g L[-1] FeSO4·7H2O, and 0.08 g L[-1] Na2EDTA were considerably lower than SOT medium, but the biomass productivity (dry weight) was comparable to SOT medium. This is explained by the heavier cell weight of the alga grown in modified seawater media compared to the alga grown in SOT medium. Furthermore, A. platensis grown in modified seawater-based medium exhibited self-flocculation and had more loosely coiled trichomes.}, } @article {pmid26518574, year = {2016}, author = {Wang, YL and Nie, JT and Chen, HM and Guo, CL and Pan, J and He, HL and Pan, JS and Cai, R}, title = {Identification and mapping of Tril, a homeodomain-leucine zipper gene involved in multicellular trichome initiation in Cucumis sativus.}, journal = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik}, volume = {129}, number = {2}, pages = {305-316}, pmid = {26518574}, issn = {1432-2242}, mesh = {Chromosome Mapping ; Cucumis sativus/*genetics/growth & development ; DNA, Plant/genetics ; Epistasis, Genetic ; Fruit/growth & development ; Gene Expression Regulation, Plant ; Genetic Markers ; Homeodomain Proteins/*genetics ; *Leucine Zippers ; Mutation ; Phenotype ; Plant Proteins/*genetics ; Transcriptome ; Trichomes/*growth & development ; }, abstract = {KEY MESSAGE: Using map-based cloning of Tril gene, we identified a homeodomain-leucine zipper gene involved in the initiation of multicellular trichomes (including the spines of fruit) in cucumber.

ABSTRACT: Fruit spines are a special type of trichome that impacts the quality and appearance of cucumber (Cucumis sativus L.) fruit. Scanning electron microscopy revealed that the trichome-less (tril) mutant originating from European greenhouse cucumber has a completely glabrous phenotype on cotyledons, hypocotyls, young leaves, fruits, and fruit stalks. Genetic analysis revealed that tril was inherited as a recessive allele at a single locus. Using 1058 F2 individuals derived from a cross between cucumber tril mutant CGN19839 and the micro-trichome (mict) mutant 06-2, tril was mapped to chromosome 6, and narrowed down to a 37.4 kb genomic region which carries seven predicted genes. Genetic and molecular analyses revealed that gene Cucsa.045360 is a possible candidate gene for the differentiation of epidermal cells to trichomes. It is a member of the class IV homeodomain-leucine zipper (HD-Zip IV) family and encodes homeodomain and START domain, sharing 66.7% predicted amino acid sequence identity to PROTODERMAL FACTOR2 (PDF2) and 35.0% to GLABRA2 (GL2) of Arabidopsis. The homeobox domain had changed amino acid sequence because of an insertion in tril mutant. The results of genetic analysis and transcriptome profiling indicated that the Tril gene had an epistatic effect on the Mict gene in trichome development. Phenotypes of the tril mutant such as glabrous fruits and female flowers at every node could be used in developing new cultivars.}, } @article {pmid26518483, year = {2016}, author = {Ninova, M and Ronshaugen, M and Griffiths-Jones, S}, title = {MicroRNA evolution, expression, and function during short germband development in Tribolium castaneum.}, journal = {Genome research}, volume = {26}, number = {1}, pages = {85-96}, pmid = {26518483}, issn = {1549-5469}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/M008908/1/MRC_/Medical Research Council/United Kingdom ; 093161/Z/10/Z/WT_/Wellcome Trust/United Kingdom ; BB/M011275/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Down-Regulation ; Drosophila/genetics ; Embryonic Development/genetics ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Gene Library ; MicroRNAs/*genetics/metabolism ; Molecular Sequence Annotation ; Sequence Analysis, RNA ; Tribolium/*embryology/*genetics ; }, abstract = {MicroRNAs are well-established players in the development of multicellular animals. Most of our understanding of microRNA function in arthropod development comes from studies in Drosophila. Despite their advantages as model systems, the long germband embryogenesis of fruit flies is an evolutionary derived state restricted to several holometabolous insect lineages. MicroRNA evolution and expression across development in animals exhibiting the ancestral and more widespread short germband mode of embryogenesis has not been characterized. We sequenced small RNA libraries of oocytes and successive intervals covering the embryonic development of the short germband model organism, Tribolium castaneum. We analyzed the evolution and temporal expression of the microRNA complement and sequenced libraries of total RNA to investigate the relationships with microRNA target expression. We show microRNA maternal loading and sequence-specific 3' end nontemplate oligoadenylation of maternally deposited microRNAs that is conserved between Tribolium and Drosophila. We further uncover large clusters encoding multiple paralogs from several Tribolium-specific microRNA families expressed during a narrow interval of time immediately after the activation of zygotic transcription. These novel microRNAs, together with several early expressed conserved microRNAs, target a significant number of maternally deposited transcripts. Comparison with Drosophila shows that microRNA-mediated maternal transcript targeting is a conserved process in insects, but the number and sequences of microRNAs involved have diverged. The expression of fast-evolving and species-specific microRNAs in the early blastoderm of T. castaneum is consistent with previous findings in Drosophila and shows that the unique permissiveness for microRNA innovation at this stage is a conserved phenomenon.}, } @article {pmid26518480, year = {2016}, author = {Keith, N and Tucker, AE and Jackson, CE and Sung, W and Lucas Lledó, JI and Schrider, DR and Schaack, S and Dudycha, JL and Ackerman, M and Younge, AJ and Shaw, JR and Lynch, M}, title = {High mutational rates of large-scale duplication and deletion in Daphnia pulex.}, journal = {Genome research}, volume = {26}, number = {1}, pages = {60-69}, pmid = {26518480}, issn = {1549-5469}, support = {R01GM036827/GM/NIGMS NIH HHS/United States ; R01 GM101672/GM/NIGMS NIH HHS/United States ; R01ES019324/ES/NIEHS NIH HHS/United States ; R01 GM036827/GM/NIGMS NIH HHS/United States ; R01GM101672-01A1/GM/NIGMS NIH HHS/United States ; R01 ES019324/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; DNA Copy Number Variations ; Daphnia/*genetics ; Evolution, Molecular ; Female ; *Gene Deletion ; *Gene Duplication ; Genetic Association Studies ; Genetic Variation ; Heterozygote ; Male ; *Mutation Rate ; Sequence Analysis, DNA ; }, abstract = {Knowledge of the genome-wide rate and spectrum of mutations is necessary to understand the origin of disease and the genetic variation driving all evolutionary processes. Here, we provide a genome-wide analysis of the rate and spectrum of mutations obtained in two Daphnia pulex genotypes via separate mutation-accumulation (MA) experiments. Unlike most MA studies that utilize haploid, homozygous, or self-fertilizing lines, D. pulex can be propagated ameiotically while maintaining a naturally heterozygous, diploid genome, allowing the capture of the full spectrum of genomic changes that arise in a heterozygous state. While base-substitution mutation rates are similar to those in other multicellular eukaryotes (about 4 × 10(-9) per site per generation), we find that the rates of large-scale (>100 kb) de novo copy-number variants (CNVs) are significantly elevated relative to those seen in previous MA studies. The heterozygosity maintained in this experiment allowed for estimates of gene-conversion processes. While most of the conversion tract lengths we report are similar to those generated by meiotic processes, we also find larger tract lengths that are indicative of mitotic processes. Comparison of MA lines to natural isolates reveals that a majority of large-scale CNVs in natural populations are removed by purifying selection. The mutations observed here share similarities with disease-causing, complex, large-scale CNVs, thereby demonstrating that MA studies in D. pulex serve as a system for studying the processes leading to such alterations.}, } @article {pmid26511015, year = {2015}, author = {Chen, H and Lin, F and Xing, K and He, X}, title = {Corrigendum: The reverse evolution from multicellularity to unicellularity during carcinogenesis.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {8812}, doi = {10.1038/ncomms9812}, pmid = {26511015}, issn = {2041-1723}, } @article {pmid26501252, year = {2015}, author = {Tan, DX and Manchester, LC and Esteban-Zubero, E and Zhou, Z and Reiter, RJ}, title = {Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism.}, journal = {Molecules (Basel, Switzerland)}, volume = {20}, number = {10}, pages = {18886-18906}, pmid = {26501252}, issn = {1420-3049}, mesh = {Animals ; Antioxidants/*metabolism ; Biosynthetic Pathways ; Humans ; Melatonin/*biosynthesis ; Oxidative Stress ; Reactive Nitrogen Species/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin's synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress.}, } @article {pmid26500611, year = {2015}, author = {Jamshidi, N and Raghunathan, A}, title = {Cell scale host-pathogen modeling: another branch in the evolution of constraint-based methods.}, journal = {Frontiers in microbiology}, volume = {6}, number = {}, pages = {1032}, pmid = {26500611}, issn = {1664-302X}, abstract = {Constraint-based models have become popular methods for systems biology as they enable the integration of complex, disparate datasets in a biologically cohesive framework that also supports the description of biological processes in terms of basic physicochemical constraints and relationships. The scope, scale, and application of genome scale models have grown from single cell bacteria to multi-cellular interaction modeling; host-pathogen modeling represents one of these examples at the current horizon of constraint-based methods. There are now a small number of examples of host-pathogen constraint-based models in the literature, however there has not yet been a definitive description of the methodology required for the functional integration of genome scale models in order to generate simulation capable host-pathogen models. Herein we outline a systematic procedure to produce functional host-pathogen models, highlighting steps which require debugging and iterative revisions in order to successfully build a functional model. The construction of such models will enable the exploration of host-pathogen interactions by leveraging the growing wealth of omic data in order to better understand mechanism of infection and identify novel therapeutic strategies.}, } @article {pmid26497146, year = {2015}, author = {Gutzwiller, F and Carmo, CR and Miller, DE and Rice, DW and Newton, IL and Hawley, RS and Teixeira, L and Bergman, CM}, title = {Dynamics of Wolbachia pipientis Gene Expression Across the Drosophila melanogaster Life Cycle.}, journal = {G3 (Bethesda, Md.)}, volume = {5}, number = {12}, pages = {2843-2856}, pmid = {26497146}, issn = {2160-1836}, support = {BB/L002817/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Cluster Analysis ; Computational Biology ; Drosophila melanogaster/*growth & development/microbiology ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; Genome, Bacterial ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions/genetics ; Life Cycle Stages ; Phylogeny ; Stress, Physiological/genetics ; Symbiosis ; Transcriptome ; Wolbachia/*genetics ; }, abstract = {Symbiotic interactions between microbes and their multicellular hosts have manifold biological consequences. To better understand how bacteria maintain symbiotic associations with animal hosts, we analyzed genome-wide gene expression for the endosymbiotic α-proteobacteria Wolbachia pipientis across the entire life cycle of Drosophila melanogaster. We found that the majority of Wolbachia genes are expressed stably across the D. melanogaster life cycle, but that 7.8% of Wolbachia genes exhibit robust stage- or sex-specific expression differences when studied in the whole-organism context. Differentially-expressed Wolbachia genes are typically up-regulated after Drosophila embryogenesis and include many bacterial membrane, secretion system, and ankyrin repeat-containing proteins. Sex-biased genes are often organized as small operons of uncharacterized genes and are mainly up-regulated in adult Drosophila males in an age-dependent manner. We also systematically investigated expression levels of previously-reported candidate genes thought to be involved in host-microbe interaction, including those in the WO-A and WO-B prophages and in the Octomom region, which has been implicated in regulating bacterial titer and pathogenicity. Our work provides comprehensive insight into the developmental dynamics of gene expression for a widespread endosymbiont in its natural host context, and shows that public gene expression data harbor rich resources to probe the functional basis of the Wolbachia-Drosophila symbiosis and annotate the transcriptional outputs of the Wolbachia genome.}, } @article {pmid26486321, year = {2016}, author = {Wagner, GP}, title = {What is "homology thinking" and what is it for?.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {326}, number = {1}, pages = {3-8}, doi = {10.1002/jez.b.22656}, pmid = {26486321}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; Developmental Biology ; Genetics, Population ; Models, Biological ; Phenotype ; Phylogeny ; }, abstract = {In this paper I examine the thesis by Marc Ereshefsky that, in evolutionary biology, there is a third style of thinking, besides the well-known "population thinking" and "tree thinking." Ereshefsky proposes "homology thinking" as a third approach, focused on the transformation of organismal phenotypes. In this short commentary, I aim at identifying the underlying biological assumptions for homology thinking and how they can be put to work in a research program within evolutionary biology. I propose that homology thinking is based on three insights: 1) multicellular organisms consist of developmentally individualized parts (sub-systems); 2) that developmental individuation entails evolutionary individuation, that is, variational quasi-independence; and 3) these individuated body parts are inherited, though indirectly, and form lineages that are recognized as homologies. These facts support a research program focused on the modification and origination of individuated body parts that supplements and puts into perspective the population genetic and phylogenetic approaches to the study of evolution.}, } @article {pmid26479715, year = {2015}, author = {Kianianmomeni, A}, title = {Potential impact of gene regulatory mechanisms on the evolution of multicellularity in the volvocine algae.}, journal = {Communicative & integrative biology}, volume = {8}, number = {2}, pages = {e1017175}, pmid = {26479715}, issn = {1942-0889}, abstract = {A fundamental question in biology is how multicellular organisms can arise from their single-celled precursors. The evolution of multicellularity requires the adoption of new traits in unicellular ancestors that allows the generation of form by, for example, increasing the size and developing new cell types. But what are the genetic, cellular and biochemical bases underlying the evolution of multicellularity? Recent advances in evolutionary developmental biology suggest that the regulation of gene expression by cis-regulatory factors, gene duplication and alternative splicing contribute to phenotypic evolution. These mechanisms enable different degrees of phenotypic divergence and complexity with variation in traits from genomes with similar gene contents. In addition, signaling pathways specific to cell types are developed to guarantee the modulation of cellular and developmental processes matched to the cell types as well as the maintenance of multicellularity.}, } @article {pmid26473020, year = {2016}, author = {Lachowiec, J and Queitsch, C and Kliebenstein, DJ}, title = {Molecular mechanisms governing differential robustness of development and environmental responses in plants.}, journal = {Annals of botany}, volume = {117}, number = {5}, pages = {795-809}, pmid = {26473020}, issn = {1095-8290}, support = {DP2 OD008371/OD/NIH HHS/United States ; T32 HG000040/HG/NHGRI NIH HHS/United States ; }, mesh = {Chromatin/genetics/metabolism ; Chromatin Assembly and Disassembly/genetics ; DNA Copy Number Variations ; DNA, Plant ; DNA, Ribosomal ; Gene Expression Regulation, Plant ; *Gene Regulatory Networks ; *Genome, Plant ; HSP90 Heat-Shock Proteins/genetics/metabolism ; Phenotype ; Plant Development/*genetics/physiology ; Plant Proteins/genetics/metabolism ; Signal Transduction ; }, abstract = {BACKGROUND: Robustness to genetic and environmental perturbation is a salient feature of multicellular organisms. Loss of developmental robustness can lead to severe phenotypic defects and fitness loss. However, perfect robustness, i.e. no variation at all, is evolutionarily unfit as organisms must be able to change phenotype to properly respond to changing environments and biotic challenges. Plasticity is the ability to adjust phenotypes predictably in response to specific environmental stimuli, which can be considered a transient shift allowing an organism to move from one robust phenotypic state to another. Plants, as sessile organisms that undergo continuous development, are particularly dependent on an exquisite fine-tuning of the processes that balance robustness and plasticity to maximize fitness.

SCOPE AND CONCLUSIONS: This paper reviews recently identified mechanisms, both systems-level and molecular, that modulate robustness, and discusses their implications for the optimization of plant fitness. Robustness in living systems arises from the structure of genetic networks, the specific molecular functions of the underlying genes, and their interactions. This very same network responsible for the robustness of specific developmental states also has to be built such that it enables plastic yet robust shifts in response to environmental changes. In plants, the interactions and functions of signal transduction pathways activated by phytohormones and the tendency for plants to tolerate whole-genome duplications, tandem gene duplication and hybridization are emerging as major regulators of robustness in development. Despite their obvious implications for plant evolution and plant breeding, the mechanistic underpinnings by which plants modulate precise levels of robustness, plasticity and evolvability in networks controlling different phenotypes are under-studied.}, } @article {pmid26465111, year = {2015}, author = {de Mendoza, A and Suga, H and Permanyer, J and Irimia, M and Ruiz-Trillo, I}, title = {Complex transcriptional regulation and independent evolution of fungal-like traits in a relative of animals.}, journal = {eLife}, volume = {4}, number = {}, pages = {e08904}, pmid = {26465111}, issn = {2050-084X}, support = {206883/ERC_/European Research Council/International ; 616960/ERC_/European Research Council/International ; }, mesh = {Animals ; *Cell Differentiation ; *Gene Expression Regulation ; Mesomycetozoea/*genetics/growth & development/*physiology ; Proteome/analysis ; }, abstract = {Cell-type specification through differential genome regulation is a hallmark of complex multicellularity. However, it remains unclear how this process evolved during the transition from unicellular to multicellular organisms. To address this question, we investigated transcriptional dynamics in the ichthyosporean Creolimax fragrantissima, a relative of animals that undergoes coenocytic development. We find that Creolimax utilizes dynamic regulation of alternative splicing, long inter-genic non-coding RNAs and co-regulated gene modules associated with animal multicellularity in a cell-type specific manner. Moreover, our study suggests that the different cell types of the three closest animal relatives (ichthyosporeans, filastereans and choanoflagellates) are the product of lineage-specific innovations. Additionally, a proteomic survey of the secretome reveals adaptations to a fungal-like lifestyle. In summary, the diversity of cell types among protistan relatives of animals and their complex genome regulation demonstrates that the last unicellular ancestor of animals was already capable of elaborate specification of cell types.}, } @article {pmid26462996, year = {2015}, author = {Kin, K}, title = {Inferring cell type innovations by phylogenetic methods-concepts, methods, and limitations.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {324}, number = {8}, pages = {653-661}, doi = {10.1002/jez.b.22657}, pmid = {26462996}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; Cell Differentiation/genetics ; Cell Lineage/genetics ; *Cells/classification/cytology ; Embryonic Development ; Gene Regulatory Networks ; *Phylogeny ; }, abstract = {Multicellular organisms are composed of distinct cell types that have specific roles in the body. Each cell type is a product of two kinds of historical processes-development and evolution. Although the concept of a cell type is difficult to define, the cell type concept based on the idea of the core regulatory network (CRN), a gene regulatory network that determines the identity of a cell type, illustrates the essential aspects of the cell type concept. The first step toward elucidating cell type evolution is to reconstruct the evolutionary relationships of cell types, or the cell type tree. The sister cell type model assumes that a new cell type evolves through divergence from a multifunctional ancestral cell type, creating tree-like evolutionary relationships between cell types. The process of generating a cell type tree can also be understood as the sequential addition of a new branching point on an ancestral cell differentiation hierarchy in evolution. A cell type tree thus represents an intertwined history of cell type evolution and development. Cell type trees can be reconstructed from high-throughput sequencing data, and the reconstruction of a cell type tree leads to the discovery of genes that are functionally important for a cell type. Although many issues including the lack of cross-species comparisons and the lack of a proper model for cell type evolution remain, the study of the origin of a new cell type using phylogenetic methods offers a promising new research avenue in developmental evolution. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 653-661, 2015. © 2015 Wiley Periodicals, Inc.}, } @article {pmid26451642, year = {2015}, author = {Stolzer, M and Siewert, K and Lai, H and Xu, M and Durand, D}, title = {Event inference in multidomain families with phylogenetic reconciliation.}, journal = {BMC bioinformatics}, volume = {16 Suppl 14}, number = {Suppl 14}, pages = {S8}, pmid = {26451642}, issn = {1471-2105}, mesh = {*Algorithms ; Animals ; *Evolution, Molecular ; Gene Duplication ; Guanylate Kinases/*genetics ; *Multigene Family ; *Phylogeny ; Protein Structure, Tertiary ; *Software ; Vertebrates/genetics ; }, abstract = {BACKGROUND: Reconstructing evolution provides valuable insights into the processes of gene evolution and function. However, while there have been great advances in algorithms and software to reconstruct the history of gene families, these tools do not model the domain shuffling events (domain duplication, insertion, transfer, and deletion) that drive the evolution of multidomain protein families. Protein evolution through domain shuffling events allows for rapid exploration of functions by introducing new combinations of existing folds. This powerful mechanism was key to some significant evolutionary innovations, such as multicellularity and the vertebrate immune system. A method for reconstructing this important evolutionary process is urgently needed.

RESULTS: Here, we introduce a novel, event-based framework for studying multidomain evolution by reconciling a domain tree with a gene tree, with additional information provided by the species tree. In the context of this framework, we present the first reconciliation algorithms to infer domain shuffling events, while addressing the challenges inherent in the inference of evolution across three levels of organization.

CONCLUSIONS: We apply these methods to the evolution of domains in the Membrane associated Guanylate Kinase family. These case studies reveal a more vivid and detailed evolutionary history than previously provided. Our algorithms have been implemented in software, freely available at http://www.cs.cmu.edu/˜durand/Notung.}, } @article {pmid26441620, year = {2015}, author = {de Wiljes, OO and van Elburg, RA and Biehl, M and Keijzer, FA}, title = {Modeling spontaneous activity across an excitable epithelium: Support for a coordination scenario of early neural evolution.}, journal = {Frontiers in computational neuroscience}, volume = {9}, number = {}, pages = {110}, pmid = {26441620}, issn = {1662-5188}, abstract = {Internal coordination models hold that early nervous systems evolved in the first place to coordinate internal activity at a multicellular level, most notably the use of multicellular contractility as an effector for motility. A recent example of such a model, the skin brain thesis, suggests that excitable epithelia using chemical signaling are a potential candidate as a nervous system precursor. We developed a computational model and a measure for whole body coordination to investigate the coordinative properties of such excitable epithelia. Using this measure we show that excitable epithelia can spontaneously exhibit body-scale patterns of activation. Relevant factors determining the extent of patterning are the noise level for exocytosis, relative body dimensions, and body size. In smaller bodies whole-body coordination emerges from cellular excitability and bidirectional excitatory transmission alone. Our results show that basic internal coordination as proposed by the skin brain thesis could have arisen in this potential nervous system precursor, supporting that this configuration may have played a role as a proto-neural system and requires further investigation.}, } @article {pmid26439347, year = {2015}, author = {Butterfield, NJ}, title = {The Neoproterozoic.}, journal = {Current biology : CB}, volume = {25}, number = {19}, pages = {R859-63}, doi = {10.1016/j.cub.2015.07.021}, pmid = {26439347}, issn = {1879-0445}, mesh = {Archaea/physiology ; Bacterial Physiological Phenomena ; *Biological Evolution ; Earth, Planet ; Eukaryota/physiology ; *Evolution, Planetary ; Fossils/anatomy & histology ; }, abstract = {The Neoproterozoic era was arguably the most revolutionary in Earth history. Extending from 1000 to 541 million years ago, it stands at the intersection of the two great tracts of evolutionary time: on the one side, some three billion years of pervasively microbial 'Precambrian' life, and on the other the modern 'Phanerozoic' biosphere with its extraordinary diversity of large multicellular organisms. The disturbance doesn't stop here, however: over this same stretch of time the planet itself was in the throes of change. Tectonically, it saw major super-continental reconfigurations, climatically its deepest ever glacial freeze, and geochemically some of the most anomalous perturbations on record. What lies behind this dramatic convergence of biological and geological phenomena, and how exactly did it give rise to the curiously complex world that we now inhabit?}, } @article {pmid26438858, year = {2015}, author = {Stefanic, P and Kraigher, B and Lyons, NA and Kolter, R and Mandic-Mulec, I}, title = {Kin discrimination between sympatric Bacillus subtilis isolates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {45}, pages = {14042-14047}, pmid = {26438858}, issn = {1091-6490}, support = {GM58218/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Bacillus subtilis/*physiology ; Base Sequence ; *Biofilms ; Cluster Analysis ; DNA Primers/genetics ; Microbial Interactions/*physiology ; Models, Genetic ; Molecular Sequence Data ; Phylogeny ; Plant Roots/*microbiology ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Kin discrimination, broadly defined as differential treatment of conspecifics according to their relatedness, could help biological systems direct cooperative behavior toward their relatives. Here we investigated the ability of the soil bacterium Bacillus subtilis to discriminate kin from nonkin in the context of swarming, a cooperative multicellular behavior. We tested a collection of sympatric conspecifics from soil in pairwise combinations and found that despite their history of coexistence, the vast majority formed distinct boundaries when the swarms met. Some swarms did merge, and most interestingly, this behavior was only seen in the most highly related strain pairs. Overall the swarm interaction phenotype strongly correlated with phylogenetic relatedness, indicative of kin discrimination. Using a subset of strains, we examined cocolonization patterns on plant roots. Pairs of kin strains were able to cocolonize roots and formed a mixed-strain biofilm. In contrast, inoculating roots with pairs of nonkin strains resulted in biofilms consisting primarily of one strain, suggestive of an antagonistic interaction among nonkin strains. This study firmly establishes kin discrimination in a bacterial multicellular setting and suggests its potential effect on ecological interactions.}, } @article {pmid26431572, year = {2015}, author = {Shklover, J and Levy-Adam, F and Kurant, E}, title = {Apoptotic Cell Clearance in Development.}, journal = {Current topics in developmental biology}, volume = {114}, number = {}, pages = {297-334}, doi = {10.1016/bs.ctdb.2015.07.024}, pmid = {26431572}, issn = {1557-8933}, mesh = {Animals ; Apoptosis/*physiology ; Caenorhabditis elegans/cytology/growth & development ; Caspases/metabolism ; Central Nervous System/cytology/*growth & development ; Drosophila melanogaster/cytology/growth & development ; Mice ; Neuroglia/cytology ; Phagocytes/*cytology/physiology ; Phagocytosis ; Signal Transduction ; Zebrafish/growth & development ; }, abstract = {Programmed cell death and its specific form apoptosis play an important role during development of multicellular organisms. They are crucial for morphogenesis and organ sculpting as well as for adjusting cell number in different systems. Removal of apoptotic cells is the last critical step of apoptosis. Apoptotic cells are properly and efficiently recognized and eliminated through phagocytosis, which is performed by professional and nonprofessional phagocytes. Phagocytosis of apoptotic cells or apoptotic cell clearance is a dynamic multistep process, involving interactions between phagocytic receptors and ligands on apoptotic cells, which are highly conserved in evolution. However, this process is extremely redundant in mammals, containing multiple factors playing similar roles in the process. Using model organisms such as Caenorhabditis elegans, Drosophila melanogaster, zebrafish, and mouse permits addressing fundamental questions in developmental cell clearance by a comprehensive approach including powerful genetics and cell biological tools enriched by live imaging. Recent studies in model organisms have enhanced significantly our understanding of the molecular and cellular basis of apoptotic cell clearance during development. Here, we review the current knowledge and illuminate the great potential of the research performed in genetic models, which opens new directions in developmental biology.}, } @article {pmid26423844, year = {2015}, author = {Drobnitch, ST and Jensen, KH and Prentice, P and Pittermann, J}, title = {Convergent evolution of vascular optimization in kelp (Laminariales).}, journal = {Proceedings. Biological sciences}, volume = {282}, number = {1816}, pages = {20151667}, pmid = {26423844}, issn = {1471-2954}, mesh = {*Biological Evolution ; Macrocystis/growth & development/*physiology ; Models, Biological ; }, abstract = {Terrestrial plants and mammals, although separated by a great evolutionary distance, have each arrived at a highly conserved body plan in which universal allometric scaling relationships govern the anatomy of vascular networks and key functional metabolic traits. The universality of allometric scaling suggests that these phyla have each evolved an 'optimal' transport strategy that has been overwhelmingly adopted by extant species. To truly evaluate the dominance and universality of vascular optimization, however, it is critical to examine other, lesser-known, vascularized phyla. The brown algae (Phaeophyceae) are one such group--as distantly related to plants as mammals, they have convergently evolved a plant-like body plan and a specialized phloem-like transport network. To evaluate possible scaling and optimization in the kelp vascular system, we developed a model of optimized transport anatomy and tested it with measurements of the giant kelp, Macrocystis pyrifera, which is among the largest and most successful of macroalgae. We also evaluated three classical allometric relationships pertaining to plant vascular tissues with a diverse sampling of kelp species. Macrocystis pyrifera displays strong scaling relationships between all tested vascular parameters and agrees with our model; other species within the Laminariales display weak or inconsistent vascular allometries. The lack of universal scaling in the kelps and the presence of optimized transport anatomy in M. pyrifera raises important questions about the evolution of optimization and the possible competitive advantage conferred by optimized vascular systems to multicellular phyla.}, } @article {pmid26416251, year = {2015}, author = {Haug, JT and Labandeira, CC and Santiago-Blay, JA and Haug, C and Brown, S}, title = {Life habits, hox genes, and affinities of a 311 million-year-old holometabolan larva.}, journal = {BMC evolutionary biology}, volume = {15}, number = {}, pages = {208}, pmid = {26416251}, issn = {1471-2148}, mesh = {Animals ; Biological Evolution ; Eye/anatomy & histology ; *Fossils ; Genes, Homeobox ; Head/anatomy & histology ; Insecta/*anatomy & histology/*genetics/growth & development/physiology ; Larva/anatomy & histology/genetics/physiology ; Phylogeny ; }, abstract = {BACKGROUND: Holometabolous insects are the most diverse, speciose and ubiquitous group of multicellular organisms in terrestrial and freshwater ecosystems. The enormous evolutionary and ecological success of Holometabola has been attributed to their unique postembryonic life phases in which nonreproductive and wingless larvae differ significantly in morphology and life habits from their reproductive and mostly winged adults, separated by a resting stage, the pupa. Little is known of the evolutionary developmental mechanisms that produced the holometabolous larval condition and their Paleozoic origin based on fossils and phylogeny.

RESULTS: We provide a detailed anatomic description of a 311 million-year-old specimen, the oldest known holometabolous larva, from the Mazon Creek deposits of Illinois, U.S.A. The head is ovoidal, downwardly oriented, broadly attached to the anterior thorax, and bears possible simple eyes and antennae with insertions encircled by molting sutures; other sutures are present but often indistinct. Mouthparts are generalized, consisting of five recognizable segments: a clypeo-labral complex, mandibles, possible hypopharynx, a maxilla bearing indistinct palp-like appendages, and labium. Distinctive mandibles are robust, triangular, and dicondylic. The thorax is delineated into three, nonoverlapping regions of distinctive surface texture, each with legs of seven elements, the terminal-most bearing paired claws. The abdomen has ten segments deployed in register with overlapping tergites; the penultimate segment bears a paired, cercus-like structure. The anterior eight segments bear clawless leglets more diminutive than the thoracic legs in length and cross-sectional diameter, and inserted more ventrolaterally than ventrally on the abdominal sidewall.

CONCLUSIONS: Srokalarva berthei occurred in an evolutionary developmental context likely responsible for the early macroevolutionary success of holometabolous insects. Srokalarva berthei bore head and prothoracic structures, leglet series on successive abdominal segments - in addition to comparable features on a second taxon eight million-years-younger - that indicates Hox-gene regulation of segmental and appendage patterning among earliest Holometabola. Srokalarva berthei body features suggest a caterpillar-like body plan and head structures indicating herbivory consistent with known, contemporaneous insect feeding damage on seed plants. Taxonomic resolution places Srokalarva berthei as an extinct lineage, apparently possessing features closer to neuropteroid than other holometabolous lineages.}, } @article {pmid26411889, year = {2015}, author = {Yu, X and Huo, L and Liu, H and Chen, L and Wang, Y and Zhu, X}, title = {Melanin is required for the formation of the multi-cellular conidia in the endophytic fungus Pestalotiopsis microspora.}, journal = {Microbiological research}, volume = {179}, number = {}, pages = {1-11}, doi = {10.1016/j.micres.2015.06.004}, pmid = {26411889}, issn = {1618-0623}, mesh = {Agrobacterium/genetics ; Fungal Proteins/genetics ; Genes, Fungal ; Germination ; Melanins/*biosynthesis/metabolism ; Microbial Viability ; Morphogenesis ; Phylogeny ; Polyketide Synthases/genetics/metabolism ; Spores, Fungal/growth & development/*physiology ; Xylariales/physiology ; }, abstract = {Melanin plays an important role in regulating various biological processes in many fungi. However, its biological role in conidiation remains largely elusive. We report here that conidia production, morphogenesis, integrity, germination and their viability in Pestalotiopsis microspora require the polyketide-derived melanin. A polyketide synthase gene, pks1, was identified and demonstrated responsible for melanin biosynthesis in this fungus. A targeted deletion mutant strain Δpks1 displayed a defect in pigmentation of conidia and had an albino colonial phenotype. Interestingly, Δpks1 produced approximately 6-fold as many conidia as the wild type did, suggesting a negative modulation of melanin on conidia production in this fungus. Moreover, the conidia failed to develop into the normal five-cell morphology, rather the three main-body cells separated via constriction at the original septum position to generate three independent mutant conidia. This result suggests a novel role of melanin in the formation of the multi-cellular conidia. Germ tubes could develop from the three different types of mutant conidia and kept elongating, despite a significantly lower germination rate was observed for them. Still more, the unpigmented conidia became permeable to Calcofluor White and DAPI, suggesting the integrity of the conidia was impaired. Deliberate inhibition of melanin biosynthesis by a specific inhibitor, tricyclazole, led to a similar phenotypes. This work demonstrates a new function of fungal melanin in conidial development.}, } @article {pmid26385555, year = {2016}, author = {Górz, A and Boroń, P}, title = {The Yeast Fungus Trichosporon lactis Found as an Epizoic Colonizer of Dung Beetle Exoskeletons.}, journal = {Microbial ecology}, volume = {71}, number = {2}, pages = {422-427}, pmid = {26385555}, issn = {1432-184X}, mesh = {Animal Shells/*microbiology ; Animals ; Coleoptera/*microbiology ; Phylogeny ; Trichosporon/classification/genetics/growth & development/*isolation & purification ; }, abstract = {The study on the biology and biodiversity of coprophagous Scarabaeoidea carried out in the Polish Carpathians revealed the occurrence of unusual epizoic excrescences on various dung beetles species of the genus Onthophagus. The excrescences occur on the elytra, prothorax, and head of the studied beetles. Detailed research on this phenomenon determined that the fungus grew in the form of multicellular thalli. The ITS-based identification of fungal material collected from beetles' exoskeletons resulted in a 100 % match with Trichosporon lactis. Until now, only a yeast lifestyle/stage was known for this basidiomycete species. Therefore, in this paper, we describe a new substrate for growth of T. lactis and its unknown and intriguing relationship with dung beetles. The results obtained in this study open up numerous research possibilities on the new role of dung beetles in terrestrial ecosystems, as well as on using the physiological properties of T. lactis to restore soils.}, } @article {pmid26381745, year = {2015}, author = {Salali, GD and Whitehouse, H and Hochberg, ME}, title = {A Life-Cycle Model of Human Social Groups Produces a U-Shaped Distribution in Group Size.}, journal = {PloS one}, volume = {10}, number = {9}, pages = {e0138496}, pmid = {26381745}, issn = {1932-6203}, mesh = {*Cultural Evolution ; *Group Processes ; Humans ; *Models, Theoretical ; *Social Behavior ; *Social Environment ; }, abstract = {One of the central puzzles in the study of sociocultural evolution is how and why transitions from small-scale human groups to large-scale, hierarchically more complex ones occurred. Here we develop a spatially explicit agent-based model as a first step towards understanding the ecological dynamics of small and large-scale human groups. By analogy with the interactions between single-celled and multicellular organisms, we build a theory of group lifecycles as an emergent property of single cell demographic and expansion behaviours. We find that once the transition from small-scale to large-scale groups occurs, a few large-scale groups continue expanding while small-scale groups gradually become scarcer, and large-scale groups become larger in size and fewer in number over time. Demographic and expansion behaviours of groups are largely influenced by the distribution and availability of resources. Our results conform to a pattern of human political change in which religions and nation states come to be represented by a few large units and many smaller ones. Future enhancements of the model should include decision-making rules and probabilities of fragmentation for large-scale societies. We suggest that the synthesis of population ecology and social evolution will generate increasingly plausible models of human group dynamics.}, } @article {pmid26379197, year = {2015}, author = {Roberts, SE and Gladfelter, AS}, title = {Nuclear autonomy in multinucleate fungi.}, journal = {Current opinion in microbiology}, volume = {28}, number = {}, pages = {60-65}, pmid = {26379197}, issn = {1879-0364}, support = {R01 GM081506/GM/NIGMS NIH HHS/United States ; R01-GM081506/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Cell Nucleus/genetics/*physiology ; *Cell Nucleus Division ; Cytoplasm/physiology ; Fungi/*genetics/growth & development/*physiology/ultrastructure ; }, abstract = {Within many fungal syncytia, nuclei behave independently despite sharing a common cytoplasm. Creation of independent nuclear zones of control in one cell is paradoxical considering random protein synthesis sites, predicted rapid diffusion rates, and well-mixed cytosol. In studying the surprising fungal nuclear autonomy, new principles of cellular organization are emerging. We discuss the current understanding of nuclear autonomy, focusing on asynchronous cell cycle progression where most work has been directed. Mechanisms underlying nuclear autonomy are diverse including mRNA localization, ploidy variability, and nuclear spacing control. With the challenges fungal syncytia face due to cytoplasmic size and shape, they serve as powerful models for uncovering new subcellular organization modes, variability sources among isogenic uninucleate cells, and the evolution of multicellularity.}, } @article {pmid26373338, year = {2015}, author = {Pascoe, B and Méric, G and Murray, S and Yahara, K and Mageiros, L and Bowen, R and Jones, NH and Jeeves, RE and Lappin-Scott, HM and Asakura, H and Sheppard, SK}, title = {Enhanced biofilm formation and multi-host transmission evolve from divergent genetic backgrounds in Campylobacter jejuni.}, journal = {Environmental microbiology}, volume = {17}, number = {11}, pages = {4779-4789}, pmid = {26373338}, issn = {1462-2920}, support = {//Wellcome Trust/United Kingdom ; 088786/C09/Z//Wellcome Trust/United Kingdom ; BB/I02464X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/L015080/1//Medical Research Council/United Kingdom ; }, mesh = {Biofilms/*growth & development ; Biological Evolution ; Campylobacter jejuni/classification/*genetics/isolation & purification ; *Genetic Background ; Genetic Variation/*genetics ; Genome-Wide Association Study ; Humans ; Oxygen/metabolism ; }, abstract = {Multicellular biofilms are an ancient bacterial adaptation that offers a protective environment for survival in hostile habitats. In microaerophilic organisms such as Campylobacter, biofilms play a key role in transmission to humans as the bacteria are exposed to atmospheric oxygen concentrations when leaving the reservoir host gut. Genetic determinants of biofilm formation differ between species, but little is known about how strains of the same species achieve the biofilm phenotype with different genetic backgrounds. Our approach combines genome-wide association studies with traditional microbiology techniques to investigate the genetic basis of biofilm formation in 102 Campylobacter jejuni isolates. We quantified biofilm formation among the isolates and identified hotspots of genetic variation in homologous sequences that correspond to variation in biofilm phenotypes. Thirteen genes demonstrated a statistically robust association including those involved in adhesion, motility, glycosylation, capsule production and oxidative stress. The genes associated with biofilm formation were different in the host generalist ST-21 and ST-45 clonal complexes, which are frequently isolated from multiple host species and clinical samples. This suggests the evolution of enhanced biofilm from different genetic backgrounds and a possible role in colonization of multiple hosts and transmission to humans.}, } @article {pmid26370559, year = {2015}, author = {Baskaran, P and Rödelsperger, C and Prabh, N and Serobyan, V and Markov, GV and Hirsekorn, A and Dieterich, C}, title = {Ancient gene duplications have shaped developmental stage-specific expression in Pristionchus pacificus.}, journal = {BMC evolutionary biology}, volume = {15}, number = {}, pages = {185}, pmid = {26370559}, issn = {1471-2148}, mesh = {Animals ; Biological Evolution ; Caenorhabditis elegans/genetics ; *Gene Duplication ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Library ; Larva/growth & development ; Multigene Family ; Nematoda/*genetics/growth & development ; Phylogeny ; }, abstract = {BACKGROUND: The development of multicellular organisms is accompanied by gene expression changes in differentiating cells. Profiling stage-specific expression during development may reveal important insights into gene sets that contributed to the morphological diversity across the animal kingdom.

RESULTS: We sequenced RNA-seq libraries throughout a developmental timecourse of the nematode Pristionchus pacificus. The transcriptomes reflect early larval stages, adult worms including late larvae, and growth-arrested dauer larvae and allowed the identification of developmentally regulated gene clusters. Our data reveals similar trends as previous transcriptome profiling of dauer worms and represents the first expression data for early larvae in P. pacificus. Gene expression clusters characterizing early larval stages show most significant enrichments of chaperones, while collagens are most significantly enriched in transcriptomes of late larvae and adult worms. By combining expression data with phylogenetic analysis, we found that developmentally regulated genes are found in paralogous clusters that have arisen through lineage-specific duplications after the split from the Caenorhabditis elegans branch.

CONCLUSIONS: We propose that gene duplications of developmentally regulated genes represent a plausible evolutionary mechanism to increase the dosage of stage-specific expression. Consequently, this may contribute to the substantial divergence in expression profiles that has been observed across larger evolutionary time scales.}, } @article {pmid26360326, year = {2015}, author = {Hale, R and Strutt, D}, title = {Conservation of Planar Polarity Pathway Function Across the Animal Kingdom.}, journal = {Annual review of genetics}, volume = {49}, number = {}, pages = {529-551}, doi = {10.1146/annurev-genet-112414-055224}, pmid = {26360326}, issn = {1545-2948}, support = {100986//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Body Patterning/physiology ; Cadherins/genetics/metabolism ; Cell Adhesion Molecules/genetics/metabolism ; Cell Polarity/*physiology ; Drosophila Proteins/genetics/*metabolism ; Signal Transduction ; Vertebrates/metabolism ; }, abstract = {Planar polarity is a well-studied phenomenon resulting in the directional coordination of cells in the plane of a tissue. In invertebrates and vertebrates, planar polarity is established and maintained by the largely independent core and Fat/Dachsous/Four-jointed (Ft-Ds-Fj) pathways. Loss of function of these pathways can result in a wide range of developmental or cellular defects, including failure of gastrulation and problems with placement and function of cilia. This review discusses the conservation of these pathways across the animal kingdom. The lack of vital core pathway components in basal metazoans suggests that the core planar polarity pathway evolved shortly after, but not necessarily alongside, the emergence of multicellularity.}, } @article {pmid26347030, year = {2015}, author = {Long, A and Liti, G and Luptak, A and Tenaillon, O}, title = {Elucidating the molecular architecture of adaptation via evolve and resequence experiments.}, journal = {Nature reviews. Genetics}, volume = {16}, number = {10}, pages = {567-582}, pmid = {26347030}, issn = {1471-0064}, support = {310944/ERC_/European Research Council/International ; R01 GM094929/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; Animals ; Bacteria/genetics ; Biological Evolution ; Drosophila melanogaster/genetics ; Epistasis, Genetic ; Evolution, Molecular ; Genetics, Microbial/methods ; Genetics, Population/*methods ; High-Throughput Nucleotide Sequencing ; Mutation ; RNA Folding ; *Selection, Genetic ; }, abstract = {Evolve and resequence (E&R) experiments use experimental evolution to adapt populations to a novel environment, then next-generation sequencing to analyse genetic changes. They enable molecular evolution to be monitored in real time on a genome-wide scale. Here, we review the field of E&R experiments across diverse systems, ranging from simple non-living RNA to bacteria, yeast and the complex multicellular organism Drosophila melanogaster. We explore how different evolutionary outcomes in these systems are largely consistent with common population genetics principles. Differences in outcomes across systems are largely explained by different starting population sizes, levels of pre-existing genetic variation, recombination rates and adaptive landscapes. We highlight emerging themes and inconsistencies that future experiments must address.}, } @article {pmid26344197, year = {2015}, author = {Wan, C and Borgeson, B and Phanse, S and Tu, F and Drew, K and Clark, G and Xiong, X and Kagan, O and Kwan, J and Bezginov, A and Chessman, K and Pal, S and Cromar, G and Papoulas, O and Ni, Z and Boutz, DR and Stoilova, S and Havugimana, PC and Guo, X and Malty, RH and Sarov, M and Greenblatt, J and Babu, M and Derry, WB and Tillier, ER and Wallingford, JB and Parkinson, J and Marcotte, EM and Emili, A}, title = {Panorama of ancient metazoan macromolecular complexes.}, journal = {Nature}, volume = {525}, number = {7569}, pages = {339-344}, pmid = {26344197}, issn = {1476-4687}, support = {F32GM112495/GM/NIGMS NIH HHS/United States ; R01 GM076536/GM/NIGMS NIH HHS/United States ; DP1 GM106408/GM/NIGMS NIH HHS/United States ; R01 GM067779/GM/NIGMS NIH HHS/United States ; //Canadian Institutes of Health Research/Canada ; F32 GM112495/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Datasets as Topic ; *Evolution, Molecular ; Humans ; Multiprotein Complexes/*chemistry/*metabolism ; Protein Interaction Mapping ; *Protein Interaction Maps ; Reproducibility of Results ; Systems Biology ; Tandem Mass Spectrometry ; }, abstract = {Macromolecular complexes are essential to conserved biological processes, but their prevalence across animals is unclear. By combining extensive biochemical fractionation with quantitative mass spectrometry, here we directly examined the composition of soluble multiprotein complexes among diverse metazoan models. Using an integrative approach, we generated a draft conservation map consisting of more than one million putative high-confidence co-complex interactions for species with fully sequenced genomes that encompasses functional modules present broadly across all extant animals. Clustering reveals a spectrum of conservation, ranging from ancient eukaryotic assemblies that have probably served cellular housekeeping roles for at least one billion years, ancestral complexes that have accrued contemporary components, and rarer metazoan innovations linked to multicellularity. We validated these projections by independent co-fractionation experiments in evolutionarily distant species, affinity purification and functional analyses. The comprehensiveness, centrality and modularity of these reconstructed interactomes reflect their fundamental mechanistic importance and adaptive value to animal cell systems.}, } @article {pmid26333839, year = {2015}, author = {Lorin, T and Salzburger, W and Böhne, A}, title = {Evolutionary Fate of the Androgen Receptor-Signaling Pathway in Ray-Finned Fishes with a Special Focus on Cichlids.}, journal = {G3 (Bethesda, Md.)}, volume = {5}, number = {11}, pages = {2275-2283}, pmid = {26333839}, issn = {2160-1836}, mesh = {Animals ; Cichlids/*genetics ; *Evolution, Molecular ; Fish Proteins/*genetics/metabolism ; Gene Duplication ; Receptors, Androgen/*genetics/metabolism ; Selection, Genetic ; Signal Transduction ; }, abstract = {The emergence of the steroid system is coupled to the evolution of multicellular animals. In vertebrates in particular, the steroid receptor repertoire has been shaped by genome duplications characteristic to this lineage. Here, we investigate for the first time the composition of the androgen receptor-signaling pathway in ray-finned fish genomes by focusing in particular on duplicates that emerged from the teleost-specific whole-genome duplication. We trace lineage- and species-specific duplications and gene losses for the genomic and nongenomic pathway of androgen signaling and subsequently investigate the sequence evolution of these genes. In one particular fish lineage, the cichlids, we find evidence for differing selection pressures acting on teleost-specific whole-genome duplication paralogs at a derived evolutionary stage. We then look into the expression of these duplicated genes in four cichlid species from Lake Tanganyika indicating, once more, rapid changes in expression patterns in closely related fish species. We focus on a particular case, the cichlid specific duplication of the rac1 GTPase, which shows possible signs of a neofunctionalization event.}, } @article {pmid26319583, year = {2015}, author = {Adams, JC and Brancaccio, A}, title = {The evolution of the dystroglycan complex, a major mediator of muscle integrity.}, journal = {Biology open}, volume = {4}, number = {9}, pages = {1163-1179}, pmid = {26319583}, issn = {2046-6390}, abstract = {Basement membrane (BM) extracellular matrices are crucial for the coordination of different tissue layers. A matrix adhesion receptor that is important for BM function and stability in many mammalian tissues is the dystroglycan (DG) complex. This comprises the non-covalently-associated extracellular α-DG, that interacts with laminin in the BM, and the transmembrane β-DG, that interacts principally with dystrophin to connect to the actin cytoskeleton. Mutations in dystrophin, DG, or several enzymes that glycosylate α-DG underlie severe forms of human muscular dystrophy. Nonwithstanding the pathophysiological importance of the DG complex and its fundamental interest as a non-integrin system of cell-ECM adhesion, the evolution of DG and its interacting proteins is not understood. We analysed the phylogenetic distribution of DG, its proximal binding partners and key processing enzymes in extant metazoan and relevant outgroups. We identify that DG originated after the divergence of ctenophores from porifera and eumetazoa. The C-terminal half of the DG core protein is highly-conserved, yet the N-terminal region, that includes the laminin-binding region, has undergone major lineage-specific divergences. Phylogenetic analysis based on the C-terminal IG2_MAT_NU region identified three distinct clades corresponding to deuterostomes, arthropods, and mollusks/early-diverging metazoans. Whereas the glycosyltransferases that modify α-DG are also present in choanoflagellates, the DG-binding proteins dystrophin and laminin originated at the base of the metazoa, and DG-associated sarcoglycan is restricted to cnidarians and bilaterians. These findings implicate extensive functional diversification of DG within invertebrate lineages and identify the laminin-DG-dystrophin axis as a conserved adhesion system that evolved subsequent to integrin-ECM adhesion, likely to enhance the functional complexity of cell-BM interactions in early metazoans.}, } @article {pmid26315993, year = {2015}, author = {Zhang, J and Debets, AJ and Verweij, PE and Melchers, WJ and Zwaan, BJ and Schoustra, SE}, title = {Asexual sporulation facilitates adaptation: The emergence of azole resistance in Aspergillus fumigatus.}, journal = {Evolution; international journal of organic evolution}, volume = {69}, number = {10}, pages = {2573-2586}, doi = {10.1111/evo.12763}, pmid = {26315993}, issn = {1558-5646}, mesh = {Adaptation, Biological/genetics ; Aspergillus fumigatus/*drug effects/*genetics ; Biological Evolution ; Drug Resistance, Multiple, Fungal/*genetics ; Fungicides, Industrial/*pharmacology ; Genes, Fungal ; *Mutation ; Reproduction, Asexual/*drug effects/*genetics ; *Selection, Genetic ; Triazoles/*pharmacology ; }, abstract = {Understanding the occurrence and spread of azole resistance in Aspergillus fumigatus is crucial for public health. It has been hypothesized that asexual sporulation, which is abundant in nature, is essential for phenotypic expression of azole resistance mutations in A. fumigatus facilitating subsequent spread through natural selection. Furthermore, the disease aspergilloma is associated with asexual sporulation within the lungs of patients and the emergence of azole resistance. This study assessed the evolutionary advantage of asexual sporulation by growing the fungus under pressure of one of five different azole fungicides over seven weeks and by comparing the rate of adaptation between scenarios of culturing with and without asexual sporulation. Results unequivocally show that asexual sporulation facilitates adaptation. This can be explained by the combination of more effective selection because of the transition from a multicellular to a unicellular stage, and by increased mutation supply due to the production of spores, which involves numerous mitotic divisions. Insights from this study are essential to unravel the resistance mechanisms of sporulating pathogens to chemical compounds and disease agents in general, and for designing strategies that prevent or overcome the emerging threat of azole resistance in particular.}, } @article {pmid26311623, year = {2015}, author = {Wegener Parfrey, L}, title = {Mock communities highlight the diversity of host-associated eukaryotes.}, journal = {Molecular ecology}, volume = {24}, number = {17}, pages = {4337-4339}, doi = {10.1111/mec.13311}, pmid = {26311623}, issn = {1365-294X}, mesh = {Animals ; Apicomplexa ; *Biodiversity ; Eukaryota ; *High-Throughput Nucleotide Sequencing ; Oligochaeta/microbiology ; *Soil Microbiology ; Symbiosis ; }, abstract = {Host-associated microbes are ubiquitous. Every multicellular eukaryote, and even many unicellular eukaryotes (protists), hosts a diverse community of microbes. High-throughput sequencing (HTS) tools have illuminated the vast diversity of host-associated microbes and shown that they have widespread influence on host biology, ecology and evolution (McFall-Ngai et al.). Bacteria receive most of the attention, but protists are also important components of microbial communities associated with humans (Parfrey et al.) and other hosts. As HTS tools are increasingly used to study eukaryotes, the presence of numerous and diverse host-associated eukaryotes is emerging as a common theme across ecosystems. Indeed, HTS studies demonstrate that host-associated lineages account for between 2 and 12% of overall eukaryotic sequences detected in soil, marine and freshwater data sets, with much higher relative abundances observed in some samples (Ramirez et al. ; Simon et al. ; de Vargas et al.). Previous studies in soil detected large numbers of predominantly parasitic lineages such as Apicomplexa, but did not delve into their origin [e.g. (Ramirez et al.)]. In this issue of Molecular Ecology, Geisen et al. () use mock communities to show that many of the eukaryotic organisms detected by environmental sequencing in soils are potentially associated with animal hosts rather than free-living. By isolating the host-associated fraction of soil microbial communities, Geisen and colleagues help explain the surprisingly high diversity of parasitic eukaryotic lineages often detected in soil/terrestrial studies using high-throughput sequencing (HTS) and reinforce the ubiquity of these host-associated microbes. It is clear that we can no longer assume that organisms detected in bulk environmental sequencing are free-living, but instead need to design studies that specifically enumerate the diversity and function of host-associated eukaryotes. Doing so will allow the field to determine the role host-associated eukaryotes play in soils and other environments and to evaluate hypotheses on assembly of host-associated communities, disease ecology and more.}, } @article {pmid26307549, year = {2015}, author = {McCormack, R and Podack, ER}, title = {Perforin-2/Mpeg1 and other pore-forming proteins throughout evolution.}, journal = {Journal of leukocyte biology}, volume = {98}, number = {5}, pages = {761-768}, pmid = {26307549}, issn = {1938-3673}, support = {F31AI106290/AI/NIAID NIH HHS/United States ; R56AI107062/AI/NIAID NIH HHS/United States ; R01 NR015649/NR/NINR NIH HHS/United States ; R01AI110810/AI/NIAID NIH HHS/United States ; R56 AI107062/AI/NIAID NIH HHS/United States ; F31 AI106290/AI/NIAID NIH HHS/United States ; R01 AI110810/AI/NIAID NIH HHS/United States ; R01NR015649/NR/NINR NIH HHS/United States ; }, mesh = {Animals ; Complement Membrane Attack Complex/*immunology ; *Evolution, Molecular ; Humans ; Membrane Proteins/*immunology ; Pore Forming Cytotoxic Proteins/*immunology ; Protein Structure, Tertiary ; }, abstract = {Development of the ancient innate immune system required not only a mechanism to recognize foreign organisms from self but also to destroy them. Pore-forming proteins containing the membrane attack complex Perforin domain were one of the first triumphs of an innate immune system needing to eliminate microbes and virally infected cells. Membrane attack complex of complement and Perforin domain proteins is unique from other immune effector molecules in that the mechanism of attack is strictly physical and unspecific. The large water-filled holes created by membrane attack complex of complement and Perforin domain pore formation allow access for additional effectors to complete the destruction of the foreign organism via chemical or enzymatic attack. Perforin-2/macrophage-expressed protein 1 is one of the oldest membrane attack complexes of complement and Perforin domain protein involved in immune defense, and it is still functional today in vertebrates. Here, we trace the impact of Perforin-2/macrophage-expressed protein 1 from the earliest multicellular organisms to modern vertebrates, as well as review the development of other membrane attack complexes of complement and Perforin domain member proteins.}, } @article {pmid26293347, year = {2015}, author = {Vázquez, E and Antequera, F}, title = {Replication dynamics in fission and budding yeasts through DNA polymerase tracking.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {37}, number = {10}, pages = {1067-1073}, pmid = {26293347}, issn = {1521-1878}, mesh = {DNA ; *DNA Replication ; DNA, Fungal/metabolism ; DNA-Directed DNA Polymerase/analysis/*metabolism ; Genome, Fungal ; Genomic Instability ; Replication Origin ; Saccharomyces cerevisiae/genetics ; Saccharomycetales/*genetics ; Schizosaccharomyces/*genetics ; }, abstract = {The dynamics of eukaryotic DNA polymerases has been difficult to establish because of the difficulty of tracking them along the chromosomes during DNA replication. Recent work has addressed this problem in the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae through the engineering of replicative polymerases to render them prone to incorporating ribonucleotides at high rates. Their use as tracers of the passage of each polymerase has provided a picture of unprecedented resolution of the organization of replicons and replication origins in the two yeasts and has uncovered important differences between them. Additional studies have found an overlapping distribution of DNA polymorphisms and the junctions of Okazaki fragments along mononucleosomal DNA. This sequence instability is caused by the premature release of polymerase δ and the retention of non proof-read DNA tracts replicated by polymerase α. The possible implementation of these new experimental approaches in multicellular organisms opens the door to the analysis of replication dynamics under a broad range of genetic backgrounds and physiological or pathological conditions.}, } @article {pmid26291327, year = {2015}, author = {Guzzo, M and Agrebi, R and Espinosa, L and Baronian, G and Molle, V and Mauriello, EM and Brochier-Armanet, C and Mignot, T}, title = {Evolution and Design Governing Signal Precision and Amplification in a Bacterial Chemosensory Pathway.}, journal = {PLoS genetics}, volume = {11}, number = {8}, pages = {e1005460}, pmid = {26291327}, issn = {1553-7404}, support = {T32ES007326/ES/NIEHS NIH HHS/United States ; U54HD055787/HD/NICHD NIH HHS/United States ; }, mesh = {Bacterial Proteins/metabolism ; Chemotaxis ; Evolution, Molecular ; Gene Expression Regulation, Bacterial ; Histidine Kinase ; Myxococcus xanthus/*physiology ; Protein Kinases/physiology ; *Signal Transduction ; }, abstract = {Understanding the principles underlying the plasticity of signal transduction networks is fundamental to decipher the functioning of living cells. In Myxococcus xanthus, a particular chemosensory system (Frz) coordinates the activity of two separate motility systems (the A- and S-motility systems), promoting multicellular development. This unusual structure asks how signal is transduced in a branched signal transduction pathway. Using combined evolution-guided and single cell approaches, we successfully uncoupled the regulations and showed that the A-motility regulation system branched-off an existing signaling system that initially only controlled S-motility. Pathway branching emerged in part following a gene duplication event and changes in the circuit structure increasing the signaling efficiency. In the evolved pathway, the Frz histidine kinase generates a steep biphasic response to increasing external stimulations, which is essential for signal partitioning to the motility systems. We further show that this behavior results from the action of two accessory response regulator proteins that act independently to filter and amplify signals from the upstream kinase. Thus, signal amplification loops may underlie the emergence of new connectivity in signal transduction pathways.}, } @article {pmid26286983, year = {2015}, author = {Godfrey-Smith, P}, title = {Reproduction, symbiosis, and the eukaryotic cell.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {33}, pages = {10120-10125}, pmid = {26286983}, issn = {1091-6490}, mesh = {Animals ; Biological Evolution ; Eukaryotic Cells/*physiology ; Humans ; Mitochondria/physiology ; Models, Biological ; *Reproduction ; Selection, Genetic ; Social Behavior ; *Symbiosis ; }, abstract = {This paper develops a conceptual framework for addressing questions about reproduction, individuality, and the units of selection in symbiotic associations, with special attention to the origin of the eukaryotic cell. Three kinds of reproduction are distinguished, and a possible evolutionary sequence giving rise to a mitochondrion-containing eukaryotic cell from an endosymbiotic partnership is analyzed as a series of transitions between each of the three forms of reproduction. The sequence of changes seen in this "egalitarian" evolutionary transition is compared with those that apply in "fraternal" transitions, such as the evolution of multicellularity in animals.}, } @article {pmid26284972, year = {2015}, author = {Du, Q and Kawabe, Y and Schilde, C and Chen, ZH and Schaap, P}, title = {The Evolution of Aggregative Multicellularity and Cell-Cell Communication in the Dictyostelia.}, journal = {Journal of molecular biology}, volume = {427}, number = {23}, pages = {3722-3733}, pmid = {26284972}, issn = {1089-8638}, support = {100293//Wellcome Trust/United Kingdom ; 100293/Z/12/Z//Wellcome Trust/United Kingdom ; BB/K000799/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Cyclic AMP/genetics/*metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cyclic GMP/analogs & derivatives/metabolism ; Dictyostelium/metabolism/*physiology ; Genome, Protozoan ; Genomics/methods ; Hexanones/metabolism ; Histidine Kinase ; Protein Kinases/metabolism ; Protozoan Proteins/genetics/*metabolism ; Quorum Sensing ; Signal Transduction ; }, abstract = {Aggregative multicellularity, resulting in formation of a spore-bearing fruiting body, evolved at least six times independently amongst both eukaryotes and prokaryotes. Amongst eukaryotes, this form of multicellularity is mainly studied in the social amoeba Dictyostelium discoideum. In this review, we summarise trends in the evolution of cell-type specialisation and behavioural complexity in the four major groups of Dictyostelia. We describe the cell-cell communication systems that control the developmental programme of D. discoideum, highlighting the central role of cAMP in the regulation of cell movement and cell differentiation. Comparative genomic studies showed that the proteins involved in cAMP signalling are deeply conserved across Dictyostelia and their unicellular amoebozoan ancestors. Comparative functional analysis revealed that cAMP signalling in D. discoideum originated from a second messenger role in amoebozoan encystation. We highlight some molecular changes in cAMP signalling genes that were responsible for the novel roles of cAMP in multicellular development.}, } @article {pmid26268215, year = {2015}, author = {Burgess, AL and David, R and Searle, IR}, title = {Conservation of tRNA and rRNA 5-methylcytosine in the kingdom Plantae.}, journal = {BMC plant biology}, volume = {15}, number = {}, pages = {199}, pmid = {26268215}, issn = {1471-2229}, mesh = {5-Methylcytosine/*metabolism ; Cell Nucleus/genetics ; Chloroplasts/genetics ; *Evolution, Molecular ; Methylation ; Methyltransferases/genetics ; Mitochondria/genetics ; Phylogeny ; Plants/*genetics/metabolism ; RNA, Transfer/*genetics/metabolism ; RNA, Untranslated/genetics ; Transcriptome ; }, abstract = {BACKGROUND: Post-transcriptional methylation of RNA cytosine residues to 5-methylcytosine (m(5)C) is an important modification that regulates RNA metabolism and occurs in both eukaryotes and prokaryotes. Yet, to date, no transcriptome-wide identification of m(5)C sites has been undertaken in plants. Plants provide a unique comparative system for investigating the origin and evolution of m(5)C as they contain three different genomes, the nucleus, mitochondria and chloroplast. Here we use bisulfite conversion of RNA combined with high-throughput IIlumina sequencing (RBS-seq) to identify single-nucleotide resolution of m(5)C sites in non-coding ribosomal RNAs and transfer RNAs of all three sub-cellular transcriptomes across six diverse species that included, the single-celled algae Nannochloropsis oculata, the macro algae Caulerpa taxifolia and multi-cellular higher plants Arabidopsis thaliana, Brassica rapa, Triticum durum and Ginkgo biloba.

RESULTS: Using the plant model Arabidopsis thaliana, we identified a total of 39 highly methylated m(5)C sites in predicted structural positions of nuclear tRNAs and 7 m(5)C sites in rRNAs from nuclear, chloroplast and mitochondrial transcriptomes. Both the nucleotide position and percent methylation of tRNAs and rRNAs m(5)C sites were conserved across all species analysed, from single celled algae N. oculata to multicellular plants. Interestingly the mitochondrial and chloroplast encoded tRNAs were devoid of m(5)C in A. thaliana and this is generally conserved across Plantae. This suggests independent evolution of organelle methylation in animals and plants, as animal mitochondrial tRNAs have m(5)C sites. Here we characterize 5 members of the RNA 5-methylcytosine family in Arabidopsis and extend the functional characterization of TRDMT1 and NOP2A/OLI2. We demonstrate that nuclear tRNA methylation requires two evolutionarily conserved methyltransferases, TRDMT1 and TRM4B. trdmt1 trm4b double mutants are hypersensitive to the antibiotic hygromycin B, demonstrating the function of tRNA methylation in regulating translation. Additionally we demonstrate that nuclear large subunit 25S rRNA methylation requires the conserved RNA methyltransferase NSUN5. Our results also suggest functional redundancy of at least two of the NOP2 paralogs in Arabidopsis.

CONCLUSIONS: Our data demonstrates widespread occurrence and conservation of non-coding RNA methylation in the kingdom Plantae, suggesting important and highly conserved roles of this post-transcriptional modification.}, } @article {pmid26254571, year = {2015}, author = {Cao, P and Dey, A and Vassallo, CN and Wall, D}, title = {How Myxobacteria Cooperate.}, journal = {Journal of molecular biology}, volume = {427}, number = {23}, pages = {3709-3721}, pmid = {26254571}, issn = {1089-8638}, support = {R01 GM101449/GM/NIGMS NIH HHS/United States ; GM101449/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Outer Membrane Proteins/*metabolism ; Myxococcales/growth & development/*physiology ; }, abstract = {Prokaryotes often reside in groups where a high degree of relatedness has allowed the evolution of cooperative behaviors. However, very few bacteria or archaea have made the successful transition from unicellular to obligate multicellular life. A notable exception is the myxobacteria, in which cells cooperate to perform group functions highlighted by fruiting body development, an obligate multicellular function. Like all multicellular organisms, myxobacteria face challenges in how to organize and maintain multicellularity. These challenges include maintaining population homeostasis, carrying out tissue repair and regulating the behavior of non-cooperators. Here, we describe the major cooperative behaviors that myxobacteria use: motility, predation and development. In addition, this review emphasizes recent discoveries in the social behavior of outer membrane exchange, wherein kin share outer membrane contents. Finally, we review evidence that outer membrane exchange may be involved in regulating population homeostasis, thus serving as a social tool for myxobacteria to make the cyclic transitions from unicellular to multicellular states.}, } @article {pmid26248158, year = {2015}, author = {Palfree, RG and Bennett, HP and Bateman, A}, title = {The Evolution of the Secreted Regulatory Protein Progranulin.}, journal = {PloS one}, volume = {10}, number = {8}, pages = {e0133749}, pmid = {26248158}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Databases, Genetic ; *Evolution, Molecular ; Fungi/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/chemistry/genetics/*metabolism ; Likelihood Functions ; Molecular Sequence Data ; Plants/metabolism ; Progranulins ; Protein Structure, Tertiary ; Sequence Alignment ; }, abstract = {Progranulin is a secreted growth factor that is active in tumorigenesis, wound repair, and inflammation. Haploinsufficiency of the human progranulin gene, GRN, causes frontotemporal dementia. Progranulins are composed of chains of cysteine-rich granulin modules. Modules may be released from progranulin by proteolysis as 6kDa granulin polypeptides. Both intact progranulin and some of the granulin polypeptides are biologically active. The granulin module occurs in certain plant proteases and progranulins are present in early diverging metazoan clades such as the sponges, indicating their ancient evolutionary origin. There is only one Grn gene in mammalian genomes. More gene-rich Grn families occur in teleost fish with between 3 and 6 members per species including short-form Grns that have no tetrapod counterparts. Our goals are to elucidate progranulin and granulin module evolution by investigating (i): the origins of metazoan progranulins (ii): the evolutionary relationships between the single Grn of tetrapods and the multiple Grn genes of fish (iii): the evolution of granulin module architectures of vertebrate progranulins (iv): the conservation of mammalian granulin polypeptide sequences and how the conserved granulin amino acid sequences map to the known three dimensional structures of granulin modules. We report that progranulin-like proteins are present in unicellular eukaryotes that are closely related to metazoa suggesting that progranulin is among the earliest extracellular regulatory proteins still employed by multicellular animals. From the genomes of the elephant shark and coelacanth we identified contemporary representatives of a precursor for short-from Grn genes of ray-finned fish that is lost in tetrapods. In vertebrate Grns pathways of exon duplication resulted in a conserved module architecture at the amino-terminus that is frequently accompanied by an unusual pattern of tandem nearly identical module repeats near the carboxyl-terminus. Polypeptide sequence conservation of mammalian granulin modules identified potential structure-activity relationships that may be informative in designing progranulin based therapeutics.}, } @article {pmid26247819, year = {2015}, author = {Ferrante, E and Turgut, AE and Duéñez-Guzmán, E and Dorigo, M and Wenseleers, T}, title = {Evolution of Self-Organized Task Specialization in Robot Swarms.}, journal = {PLoS computational biology}, volume = {11}, number = {8}, pages = {e1004273}, pmid = {26247819}, issn = {1553-7358}, mesh = {Animals ; Ants/physiology ; *Artificial Intelligence ; *Biological Evolution ; Computational Biology ; *Models, Biological ; *Robotics/instrumentation/methods ; *Social Behavior ; Task Performance and Analysis ; Work ; }, abstract = {Division of labor is ubiquitous in biological systems, as evidenced by various forms of complex task specialization observed in both animal societies and multicellular organisms. Although clearly adaptive, the way in which division of labor first evolved remains enigmatic, as it requires the simultaneous co-occurrence of several complex traits to achieve the required degree of coordination. Recently, evolutionary swarm robotics has emerged as an excellent test bed to study the evolution of coordinated group-level behavior. Here we use this framework for the first time to study the evolutionary origin of behavioral task specialization among groups of identical robots. The scenario we study involves an advanced form of division of labor, common in insect societies and known as "task partitioning", whereby two sets of tasks have to be carried out in sequence by different individuals. Our results show that task partitioning is favored whenever the environment has features that, when exploited, reduce switching costs and increase the net efficiency of the group, and that an optimal mix of task specialists is achieved most readily when the behavioral repertoires aimed at carrying out the different subtasks are available as pre-adapted building blocks. Nevertheless, we also show for the first time that self-organized task specialization could be evolved entirely from scratch, starting only from basic, low-level behavioral primitives, using a nature-inspired evolutionary method known as Grammatical Evolution. Remarkably, division of labor was achieved merely by selecting on overall group performance, and without providing any prior information on how the global object retrieval task was best divided into smaller subtasks. We discuss the potential of our method for engineering adaptively behaving robot swarms and interpret our results in relation to the likely path that nature took to evolve complex sociality and task specialization.}, } @article {pmid26247630, year = {2015}, author = {Le, LT and Couvet, M and Favier, B and Coll, JL and Nguyen, CH and Molla, A}, title = {Discovery of benzo[e]pyridoindolones as kinase inhibitors that disrupt mitosis exit while erasing AMPK-Thr172 phosphorylation on the spindle.}, journal = {Oncotarget}, volume = {6}, number = {26}, pages = {22152-22166}, pmid = {26247630}, issn = {1949-2553}, mesh = {AMP-Activated Protein Kinases/*antagonists & inhibitors ; Animals ; Aurora Kinase B/*antagonists & inhibitors ; Drug Screening Assays, Antitumor ; Female ; HeLa Cells ; Human Umbilical Vein Endothelial Cells ; Humans ; Indoles/chemistry/*pharmacology ; Mice ; Mitosis/*drug effects ; Phosphorylation/drug effects ; Protein Kinase Inhibitors/*pharmacology ; Pyridines/chemistry/*pharmacology ; Random Allocation ; Spheroids, Cellular ; Xenograft Model Antitumor Assays ; }, abstract = {Aurora kinases play an essential role in mitotic progression and are attractive targets in cancer therapy. The first generation of benzo[e]pyridoindole exhibited powerful aurora kinase inhibition but their low solubility limited further development. Grafting a pyperidine-ethoxy group gives rise to a hydrosoluble inhibitor: compound C5M.C5M could efficiently inhibit the proliferation of cells from different origins. C5M prevented cell cycling, induced a strong mitotic arrest then, cells became polyploid and finally died. C5M did not impair the spindle checkpoint, the separation of the sister chromatids and the transfer of aurora B on the mid-zone. C5M prevented histone H3 phosphorylation at mitotic entry and erased AMPK-Thr172 phosphorylation in late mitosis. With this unique profile of inhibition, C5M could be useful for understanding the role of phospho-Thr172-AMPK in abscission and the relationship between the chromosomal complex and the energy sensing machinery.C5M is a multikinase inhibitor with interesting preclinical characteristics: high hydro-solubility and a good stability in plasma. A single dose prevents the expansion of multicellular spheroids. C5M can safely be injected to mice and reduces significantly the development of xenograft. The next step will be to define the protocol of treatment and the cancer therapeutic field of this new anti-proliferative drug.}, } @article {pmid26246549, year = {2015}, author = {Biernaskie, JM and West, SA}, title = {Cooperation, clumping and the evolution of multicellularity.}, journal = {Proceedings. Biological sciences}, volume = {282}, number = {1813}, pages = {20151075}, pmid = {26246549}, issn = {1471-2954}, mesh = {*Biological Evolution ; *Microbial Interactions ; Models, Biological ; }, abstract = {The evolution of multicellular organisms represents one of the major evolutionary transitions in the history of life. A potential advantage of forming multicellular clumps is that it provides an efficiency benefit to pre-existing cooperation, such as the production of extracellular 'public goods'. However, this is complicated by the fact that cooperation could jointly evolve with clumping, and clumping could have multiple consequences for the evolution of cooperation. We model the evolution of clumping and a cooperative public good, showing that (i) when considered separately, both clumping and public goods production gradually increase with increasing genetic relatedness; (ii) in contrast, when the traits evolve jointly, a small increase in relatedness can lead to a major shift in evolutionary outcome—from a non-clumping state with low public goods production to a cooperative clumping state with high values of both traits; (iii) high relatedness makes it easier to get to the cooperative clumping state and (iv) clumping can be inhibited when it increases the number of cells that the benefits of cooperation must be shared with, but promoted when it increases relatedness between those cells. Overall, our results suggest that public goods sharing can facilitate the formation of well-integrated cooperative clumps as a first step in the evolution of multicellularity.}, } @article {pmid26245677, year = {2015}, author = {Yang, EC and Kim, KM and Kim, SY and Lee, J and Boo, GH and Lee, JH and Nelson, WA and Yi, G and Schmidt, WE and Fredericq, S and Boo, SM and Bhattacharya, D and Yoon, HS}, title = {Highly Conserved Mitochondrial Genomes among Multicellular Red Algae of the Florideophyceae.}, journal = {Genome biology and evolution}, volume = {7}, number = {8}, pages = {2394-2406}, pmid = {26245677}, issn = {1759-6653}, mesh = {Conserved Sequence ; *Evolution, Molecular ; *Genome, Mitochondrial ; Molecular Sequence Data ; Phylogeny ; Plant Proteins/genetics ; Rhodophyta/classification/*genetics ; Synteny ; }, abstract = {Two red algal classes, the Florideophyceae (approximately 7,100 spp.) and Bangiophyceae (approximately 193 spp.), comprise 98% of red algal diversity in marine and freshwater habitats. These two classes form well-supported monophyletic groups in most phylogenetic analyses. Nonetheless, the interordinal relationships remain largely unresolved, in particular in the largest subclass Rhodymeniophycidae that includes 70% of all species. To elucidate red algal phylogenetic relationships and study organelle evolution, we determined the sequence of 11 mitochondrial genomes (mtDNA) from 5 florideophycean subclasses. These mtDNAs were combined with existing data, resulting in a database of 25 florideophytes and 12 bangiophytes (including cyanidiophycean species). A concatenated alignment of mt proteins was used to resolve ordinal relationships in the Rhodymeniophycidae. Red algal mtDNA genome comparisons showed 47 instances of gene rearrangement including 12 that distinguish Bangiophyceae from Hildenbrandiophycidae, and 5 that distinguish Hildenbrandiophycidae from Nemaliophycidae. These organelle data support a rapid radiation and surprisingly high conservation of mtDNA gene syntheny among the morphologically divergent multicellular lineages of Rhodymeniophycidae. In contrast, we find extensive mitochondrial gene rearrangements when comparing Bangiophyceae and Florideophyceae and multiple examples of gene loss among the different red algal lineages.}, } @article {pmid26244002, year = {2015}, author = {Zhong, B and Sun, L and Penny, D}, title = {The Origin of Land Plants: A Phylogenomic Perspective.}, journal = {Evolutionary bioinformatics online}, volume = {11}, number = {}, pages = {137-141}, pmid = {26244002}, issn = {1176-9343}, abstract = {Land plants are a natural group, and Charophyte algae are the closest lineages of land plants and have six morphologically diverged groups. The conjugating green algae (Zygnematales) are now suggested to be the extant sister group to land plants, providing the novel understanding for character evolution and early multicellular innovations in land plants. We review recent molecular phylogenetic work on the origin of land plants and discuss some future directions in phylogenomic analyses.}, } @article {pmid26239915, year = {2015}, author = {Sinkovics, JG}, title = {The cnidarian origin of the proto-oncogenes NF-κB/STAT and WNT-like oncogenic pathway drives the ctenophores (Review).}, journal = {International journal of oncology}, volume = {47}, number = {4}, pages = {1211-1229}, pmid = {26239915}, issn = {1791-2423}, mesh = {Animals ; Cnidaria/*physiology ; Ctenophora/*physiology ; Humans ; Lymphoma/*metabolism ; NF-kappa B/*metabolism ; Proto-Oncogenes/physiology ; Wnt Proteins/*metabolism ; Wnt Signaling Pathway/*physiology ; }, abstract = {The cell survival pathways of the diploblastic early multicellular eukaryotic hosts contain and operate the molecular machinery resembling those of malignantly transformed individual cells of highly advanced multicellular hosts (including Homo). In the present review, the STAT/NF-κB pathway of the cnidarian Nematostella vectensis is compared with that of human tumors (malignant lymphomas, including Reed-Sternberg cells) pointing out similarities, including possible viral initiation in both cases. In the ctenophore genome and proteome, β-catenin gains intranuclear advantages due to a physiologically weak destructive complex in the cytoplasm, and lack of natural inhibitors (the dickkopfs). Thus, a scenario similar to what tumor cells initiate and achieve is presented through several constitutive loss-of-function type mutations in the destructive complex and in the elimination of inhibitors. Vice versa, malignantly transformed individual cells of advanced multicellular hosts assume pheno-genotypic resemblance to cells of unicellular or early multicellular hosts, and presumably to their ancient predecessors, by returning to the semblance of immortality and to the resumption of the state of high degree of resistance to physicochemical insults. Human leukemogenic and oncogenic pathways are presented for comparisons. The supreme bioengineers RNA/DNA complex encoded both the malignantly transformed immortal cell and the human cerebral cortex. The former generates molecules for the immortality of cellular life in the Universe. The latter invents the inhibitors of the process in order to gain control over it.}, } @article {pmid26237574, year = {2015}, author = {Singh, RK and Pandey, SP}, title = {Evolution of structural and functional diversification among plant Argonautes.}, journal = {Plant signaling & behavior}, volume = {10}, number = {10}, pages = {e1069455}, pmid = {26237574}, issn = {1559-2324}, mesh = {Argonaute Proteins/*genetics/metabolism ; Biological Evolution ; Bryophyta/genetics/metabolism ; Chlamydomonas/genetics/metabolism ; *Evolution, Molecular ; *Gene Expression Regulation, Plant ; *Gene Silencing ; *Genes, Plant ; Oryza/genetics/metabolism ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Plants/*genetics/metabolism ; }, abstract = {Argonautes (AGOs) are the effector proteins of the RNA-induced silencing (RISC) complex, formed during the phenomena of small-RNA mediated post-transcriptional gene silencing. AGOs are a large family of proteins; their number varies from a few (4 in Chlamydomonas reinhardtii) to many (18 in Oryza sativa) in plants. Genetics-guided analysis have demonstrated the roles of some of the AGOs during growth and development of plants. Biochemical studies have further revealed differences in functional specificities among AGOs. How the AGO family expanded in different plant species during the course of evolution is starting to emerge. We hypothesized that 4 classes of AGOs evolved after divergence of unicellular green algae when an ancestral AGO underwent duplication events. Evolution of multicellularity may have coincided with the diversification of AGOs. A comparative sequence and structure analysis of the plant AGOs, including those from the mosses and the unicellular algae, show not only conformational differences between those from lower and higher plants, but also functional divergence of important sites.}, } @article {pmid26227665, year = {2015}, author = {Park, S and Lehner, B}, title = {Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell types.}, journal = {Molecular systems biology}, volume = {11}, number = {7}, pages = {824}, pmid = {26227665}, issn = {1744-4292}, mesh = {Cell Plasticity ; *Epistasis, Genetic ; Gene Expression Regulation, Neoplastic ; *Genes, Neoplasm ; Genetic Predisposition to Disease ; Humans ; Neoplasms/*genetics ; Polymorphism, Single Nucleotide ; }, abstract = {Cancers, like many diseases, are normally caused by combinations of genetic alterations rather than by changes affecting single genes. It is well established that the genetic alterations that drive cancer often interact epistatically, having greater or weaker consequences in combination than expected from their individual effects. In a stringent statistical analysis of data from > 3,000 tumors, we find that the co-occurrence and mutual exclusivity relationships between cancer driver alterations change quite extensively in different types of cancer. This cannot be accounted for by variation in tumor heterogeneity or unrecognized cancer subtypes. Rather, it suggests that how genomic alterations interact cooperatively or partially redundantly to driver cancer changes in different types of cancers. This re-wiring of epistasis across cell types is likely to be a basic feature of genetic architecture, with important implications for understanding the evolution of multicellularity and human genetic diseases. In addition, if this plasticity of epistasis across cell types is also true for synthetic lethal interactions, a synthetic lethal strategy to kill cancer cells may frequently work in one type of cancer but prove ineffective in another.}, } @article {pmid26216949, year = {2015}, author = {Chen, L and Rashid, F and Shah, A and Awan, HM and Wu, M and Liu, A and Wang, J and Zhu, T and Luo, Z and Shan, G}, title = {The isolation of an RNA aptamer targeting to p53 protein with single amino acid mutation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {32}, pages = {10002-10007}, pmid = {26216949}, issn = {1091-6490}, mesh = {Administration, Intravenous ; Amino Acid Substitution ; Amino Acids/*genetics ; Animals ; Aptamers, Nucleotide/*isolation & purification ; Base Sequence ; Cell Proliferation ; Enzyme-Linked Immunosorbent Assay ; HEK293 Cells ; HeLa Cells ; Humans ; Mice ; Molecular Sequence Data ; Mutant Proteins/metabolism ; Mutation/*genetics ; Nanoparticles/chemistry ; Neoplasms/pathology ; SELEX Aptamer Technique ; Tumor Suppressor Protein p53/*genetics/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {p53, known as a tumor suppressor, is a DNA binding protein that regulates cell cycle, activates DNA repair proteins, and triggers apoptosis in multicellular animals. More than 50% of human cancers contain a mutation or deletion of the p53 gene, and p53R175 is one of the hot spots of p53 mutation. Nucleic acid aptamers are short single-stranded oligonucleotides that are able to bind various targets, and they are typically isolated from an experimental procedure called systematic evolution of ligand exponential enrichment (SELEX). Using a previously unidentified strategy of contrast screening with SELEX, we have isolated an RNA aptamer targeting p53R175H. This RNA aptamer (p53R175H-APT) has a significantly stronger affinity to p53R175H than to the wild-type p53 in both in vitro and in vivo assays. p53R175H-APT decreased the growth rate, weakened the migration capability, and triggered apoptosis in human lung cancer cells harboring p53R175H. Further analysis actually indicated that p53R175H-APT might partially rescue or correct the p53R175H to function more like the wild-type p53. In situ injections of p53R175H-APT to the tumor xenografts confirmed the effects of this RNA aptamer on p53R175H mutation in mice.}, } @article {pmid26206087, year = {2016}, author = {Causeret, F and Sumia, I and Pierani, A}, title = {Kremen1 and Dickkopf1 control cell survival in a Wnt-independent manner.}, journal = {Cell death and differentiation}, volume = {23}, number = {2}, pages = {323-332}, pmid = {26206087}, issn = {1476-5403}, mesh = {Animals ; Apoptosis ; Cell Survival ; Embryo Culture Techniques ; Evolution, Molecular ; HEK293 Cells ; Humans ; Intercellular Signaling Peptides and Proteins/*physiology ; Membrane Proteins/*physiology ; Mice ; Mutation ; Neoplasms/genetics ; Wnt Proteins/metabolism ; *Wnt Signaling Pathway ; }, abstract = {In multicellular organisms, a tight control of cell death is required to ensure normal development and tissue homeostasis. Improper function of apoptotic or survival pathways can not only affect developmental programs but also favor cancer progression. Here we describe a novel apoptotic signaling pathway involving the transmembrane receptor Kremen1 and its ligand, the Wnt-antagonist Dickkopf1. Using a whole embryo culture system, we first show that Dickkopf1 treatment promotes cell survival in a mouse model exhibiting increased apoptosis in the developing neural plate. Remarkably, this effect was not recapitulated by chemical Wnt inhibition. We then show that Dickkopf1 receptor Kremen1 is a bona fide dependence receptor, triggering cell death unless bound to its ligand. We performed Wnt-activity assays to demonstrate that the pro-apoptotic and anti-Wnt functions mediated by Kremen1 are strictly independent. Furthermore, we combined phylogenetic and mutagenesis approaches to identify a specific motif in the cytoplasmic tail of Kremen1, which is (i) specifically conserved in the lineage of placental mammals and (ii) strictly required for apoptosis induction. Finally, we show that somatic mutations of kremen1 found in human cancers can affect its pro-apoptotic activity, supporting a tumor suppressor function. Our findings thus reveal a new Wnt-independent function for Kremen1 and Dickkopf1 in the regulation of cell survival with potential implications in cancer therapies.}, } @article {pmid26199361, year = {2015}, author = {Nores, MJ and López, HA and Anton, AM and Rudall, PJ}, title = {Contrasting models of the female reproductive tract in four o'clocks (Nyctaginaceae).}, journal = {American journal of botany}, volume = {102}, number = {7}, pages = {1026-1039}, doi = {10.3732/ajb.1400521}, pmid = {26199361}, issn = {1537-2197}, mesh = {Biological Evolution ; Cluster Analysis ; Fertilization ; Flowers/genetics/*ultrastructure ; *Models, Structural ; Nyctaginaceae/genetics/*ultrastructure ; Pollen Tube/genetics/ultrastructure ; Pollination ; Reproduction ; Species Specificity ; }, abstract = {UNLABELLED: •

PREMISE OF THE STUDY: In angiosperms, several carpel tissues are specialized to facilitate pollen-tube elongation to achieve fertilization. We evaluated the possible evolutionary pathways of the diverse female reproductive tracts in Nyctaginaceae.•

METHODS: We studied the anatomy of a range of species representing different tribes, using light, fluorescence, scanning electron, and transmission electron microscopy.•

KEY RESULTS: Stigmas have multicellular, multiseriate papillae, except for Boerhavia diffusa with unicellular papillae. The styles are solid, with a strand of transmitting tissue linking the stigma with the ventral ovary wall. In Allionia, Boerhavia, and Mirabilis, the transmitting tissue branches into two independent tracts at the base of the ovary and continues across the lateral margins of the funicle to the micropyle; it is composed of cells with thick walls surrounded by abundant extracellular matrix. Bougainvillea, Pisonia, and Pisoniella have a diffuse transmitting tissue and an obturator, a proliferation of cells covered by a layer of secretory papillae that encloses the funicle, placenta, and ventral wall of the gynoecium and contacts with the micropyle.•

CONCLUSIONS: We propose two models of female reproductive tract, (A) one in which an obturator is absent and the transmitting tissue is compact and branched and (B) one in which an obturator is present and the transmitting tissue is diffuse. On the basis of character optimization, we hypothesize that model B represents the ancestral (plesiomorphic) condition in the family and model A originated once during evolution, within the tribe Nyctagineae.}, } @article {pmid26198319, year = {2015}, author = {Ramilowski, JA and Goldberg, T and Harshbarger, J and Kloppmann, E and Lizio, M and Satagopam, VP and Itoh, M and Kawaji, H and Carninci, P and Rost, B and Forrest, AR}, title = {A draft network of ligand-receptor-mediated multicellular signalling in human.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {7866}, pmid = {26198319}, issn = {2041-1723}, support = {U54 GM095315/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Cell Communication ; Evolution, Molecular ; Humans ; Ligands ; Receptors, Cell Surface/*metabolism ; Software ; }, abstract = {Cell-to-cell communication across multiple cell types and tissues strictly governs proper functioning of metazoans and extensively relies on interactions between secreted ligands and cell-surface receptors. Herein, we present the first large-scale map of cell-to-cell communication between 144 human primary cell types. We reveal that most cells express tens to hundreds of ligands and receptors to create a highly connected signalling network through multiple ligand-receptor paths. We also observe extensive autocrine signalling with approximately two-thirds of partners possibly interacting on the same cell type. We find that plasma membrane and secreted proteins have the highest cell-type specificity, they are evolutionarily younger than intracellular proteins, and that most receptors had evolved before their ligands. We provide an online tool to interactively query and visualize our networks and demonstrate how this tool can reveal novel cell-to-cell interactions with the prediction that mast cells signal to monoblastic lineages via the CSF1-CSF1R interacting pair.}, } @article {pmid26195746, year = {2015}, author = {Speijer, D and Lukeš, J and Eliáš, M}, title = {Sex is a ubiquitous, ancient, and inherent attribute of eukaryotic life.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {29}, pages = {8827-8834}, pmid = {26195746}, issn = {1091-6490}, mesh = {Cell Fusion ; Eukaryotic Cells/*physiology ; Genome ; Meiosis ; Mitochondria/metabolism ; Molecular Sequence Data ; Reactive Oxygen Species/metabolism ; *Reproduction ; Sequence Analysis, DNA ; }, abstract = {Sexual reproduction and clonality in eukaryotes are mostly seen as exclusive, the latter being rather exceptional. This view might be biased by focusing almost exclusively on metazoans. We analyze and discuss reproduction in the context of extant eukaryotic diversity, paying special attention to protists. We present results of phylogenetically extended searches for homologs of two proteins functioning in cell and nuclear fusion, respectively (HAP2 and GEX1), providing indirect evidence for these processes in several eukaryotic lineages where sex has not been observed yet. We argue that (i) the debate on the relative significance of sex and clonality in eukaryotes is confounded by not appropriately distinguishing multicellular and unicellular organisms; (ii) eukaryotic sex is extremely widespread and already present in the last eukaryotic common ancestor; and (iii) the general mode of existence of eukaryotes is best described by clonally propagating cell lines with episodic sex triggered by external or internal clues. However, important questions concern the relative longevity of true clonal species (i.e., species not able to return to sexual procreation anymore). Long-lived clonal species seem strikingly rare. We analyze their properties in the light of meiotic sex development from existing prokaryotic repair mechanisms. Based on these considerations, we speculate that eukaryotic sex likely developed as a cellular survival strategy, possibly in the context of internal reactive oxygen species stress generated by a (proto) mitochondrion. Thus, in the context of the symbiogenic model of eukaryotic origin, sex might directly result from the very evolutionary mode by which eukaryotic cells arose.}, } @article {pmid26194954, year = {2015}, author = {Wynns, AA}, title = {Convergent evolution of highly reduced fruiting bodies in Pezizomycotina suggests key adaptations to the bee habitat.}, journal = {BMC evolutionary biology}, volume = {15}, number = {}, pages = {145}, pmid = {26194954}, issn = {1471-2148}, mesh = {Animals ; Ascomycota/*classification/genetics/*isolation & purification/physiology ; Bees/microbiology/*physiology ; *Biological Evolution ; DNA, Fungal/genetics ; DNA, Ribosomal/genetics ; Ecosystem ; Phylogeny ; }, abstract = {BACKGROUND: Among the understudied fungi found in nature are those living in close association with social and solitary bees. The bee-specialist genera Bettsia, Ascosphaera and Eremascus are remarkable not only for their specialized niche but also for their simple fruiting bodies or ascocarps, which are morphologically anomalous in Pezizomycotina. Bettsia and Ascosphaera are characterized by a unicellular cyst-like cleistothecium known as a spore cyst, while Eremascus is characterized by completely naked asci, or asci not formed within a protective ascocarp. Before molecular phylogenetics the placement of these genera within Pezizomycotina remained tentative; morphological characters were misleading because they do not produce multicellular ascocarps, a defining character of Pezizomycotina. Because of their unique fruiting bodies, the close relationship of these bee-specialist fungi and their monophyly appeared certain. However, recent molecular studies have shown that Bettsia is not closely related to Ascosphaera. In this study, I isolated the very rare fungus Eremascus fertilis (Ascomycota, Pezizomycotina) from the bee bread of honey bees. These isolates represent the second report of E. fertilis both in nature and in the honey bee hive. To establish the systematic position of E. fertilis and Bettsia alvei, I performed phylogenetic analyses of nuclear ribosomal LSU + SSU DNA sequences from these species and 63 additional ascomycetes.

RESULTS: The phylogenetic analyses revealed that Eremascus is not monophyletic. Eremascus albus is closely related to Ascosphaera in Eurotiomycetes while E. fertilis belongs in Myxotrichaceae, a putative member of Leotiomycetes. Bettsia is not closely related to Ascosphaera and like E. fertilis apparently belongs in Leotiomycetes. These results indicate that both the naked ascus and spore cyst evolved twice in the Pezizomycotina and in distantly related lineages. The new genus Skoua is described to accommodate E. fertilis.

CONCLUSIONS: The naked ascus and spore cyst are both shown to have evolved convergently within the bee habitat. The convergent evolution of these unusual ascocarps is hypothesized to be adaptive for bee-mediated dispersal. Elucidating the dispersal strategies of these fungal symbionts contributes to our understanding of their interaction with bees and provides insight into the factors which potentially drive the evolution of reduced ascocarps in Pezizomycotina.}, } @article {pmid26193902, year = {2015}, author = {Greaves, M}, title = {Evolutionary determinants of cancer.}, journal = {Cancer discovery}, volume = {5}, number = {8}, pages = {806-820}, pmid = {26193902}, issn = {2159-8290}, support = {//Wellcome Trust/United Kingdom ; 105104//Wellcome Trust/United Kingdom ; 11021/LLR_/Blood Cancer UK/United Kingdom ; 105104/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Clonal Evolution ; Evolution, Molecular ; Humans ; Neoplasms/epidemiology/*etiology ; Neoplastic Stem Cells/metabolism ; Risk ; }, abstract = {UNLABELLED: Our understanding of cancer is being transformed by exploring clonal diversity, drug resistance, and causation within an evolutionary framework. The therapeutic resilience of advanced cancer is a consequence of its character as a complex, dynamic, and adaptive ecosystem engendering robustness, underpinned by genetic diversity and epigenetic plasticity. The risk of mutation-driven escape by self-renewing cells is intrinsic to multicellularity but is countered by multiple restraints, facilitating increasing complexity and longevity of species. But our own species has disrupted this historical narrative by rapidly escalating intrinsic risk. Evolutionary principles illuminate these challenges and provide new avenues to explore for more effective control.

SIGNIFICANCE: Lifetime risk of cancer now approximates to 50% in Western societies. And, despite many advances, the outcome for patients with disseminated disease remains poor, with drug resistance the norm. An evolutionary perspective may provide a clearer understanding of how cancer clones develop robustness and why, for us as a species, risk is now off the scale. And, perhaps, of what we might best do to achieve more effective control.}, } @article {pmid26184597, year = {2015}, author = {Soucy, SM and Huang, J and Gogarten, JP}, title = {Horizontal gene transfer: building the web of life.}, journal = {Nature reviews. Genetics}, volume = {16}, number = {8}, pages = {472-482}, pmid = {26184597}, issn = {1471-0064}, mesh = {Eukaryota/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics/*physiology ; *Models, Genetic ; *Phylogeny ; *Selection, Genetic ; Symbiosis/*genetics ; }, abstract = {Horizontal gene transfer (HGT) is the sharing of genetic material between organisms that are not in a parent-offspring relationship. HGT is a widely recognized mechanism for adaptation in bacteria and archaea. Microbial antibiotic resistance and pathogenicity are often associated with HGT, but the scope of HGT extends far beyond disease-causing organisms. In this Review, we describe how HGT has shaped the web of life using examples of HGT among prokaryotes, between prokaryotes and eukaryotes, and even between multicellular eukaryotes. We discuss replacement and additive HGT, the proposed mechanisms of HGT, selective forces that influence HGT, and the evolutionary impact of HGT on ancestral populations and existing populations such as the human microbiome.}, } @article {pmid26178988, year = {2015}, author = {Gutiérrez, S and Pirolles, E and Yvon, M and Baecker, V and Michalakis, Y and Blanc, S}, title = {The Multiplicity of Cellular Infection Changes Depending on the Route of Cell Infection in a Plant Virus.}, journal = {Journal of virology}, volume = {89}, number = {18}, pages = {9665-9675}, pmid = {26178988}, issn = {1098-5514}, mesh = {Animals ; Aphids/virology ; Brassica rapa/metabolism/*virology ; Genome, Viral/*physiology ; Plant Leaves/metabolism/*virology ; Tymovirus/*physiology ; *Viral Tropism ; }, abstract = {UNLABELLED: The multiplicity of cellular infection (MOI) is the number of virus genomes of a given virus species that infect individual cells. This parameter chiefly impacts the severity of within-host population bottlenecks as well as the intensity of genetic exchange, competition, and complementation among viral genotypes. Only a few formal estimations of the MOI currently are available, and most theoretical reports have considered this parameter as constant within the infected host. Nevertheless, the colonization of a multicellular host is a complex process during which the MOI may dramatically change in different organs and at different stages of the infection. We have used both qualitative and quantitative approaches to analyze the MOI during the colonization of turnip plants by Turnip mosaic virus. Remarkably, different MOIs were observed at two phases of the systemic infection of a leaf. The MOI was very low in primary infections from virus circulating within the vasculature, generally leading to primary foci founded by a single genome. Each lineage then moved from cell to cell at a very high MOI. Despite this elevated MOI during cell-to-cell progression, coinfection of cells by lineages originating in different primary foci is severely limited by the rapid onset of a mechanism inhibiting secondary infection. Thus, our results unveil an intriguing colonization pattern where individual viral genomes initiate distinct lineages within a leaf. Kin genomes then massively coinfect cells, but coinfection by two distinct lineages is strictly limited.

IMPORTANCE: The MOI is the size of the viral population colonizing cells and defines major phenomena in virus evolution, like the intensity of genetic exchange and the size of within-host population bottlenecks. However, few studies have quantified the MOI, and most consider this parameter as constant during infection. Our results reveal that the MOI can depend largely on the route of cell infection in a systemically infected leaf. The MOI is usually one genome per cell when cells are infected from virus particles moving long distances in the vasculature, whereas it is much higher during subsequent cell-to-cell movement in mesophyll. However, a fast-acting superinfection exclusion prevents cell coinfection by merging populations originating from different primary foci within a leaf. This complex colonization pattern results in a situation where within-cell interactions are occurring almost exclusively among kin and explains the common but uncharacterized phenomenon of genotype spatial segregation in infected plants.}, } @article {pmid26173445, year = {2015}, author = {Arenas-Mena, C and Coffman, JA}, title = {Developmental control of transcriptional and proliferative potency during the evolutionary emergence of animals.}, journal = {Developmental dynamics : an official publication of the American Association of Anatomists}, volume = {244}, number = {10}, pages = {1193-1201}, pmid = {26173445}, issn = {1097-0177}, support = {P20 GM103423/GM/NIGMS NIH HHS/United States ; P20 GM104318/GM/NIGMS NIH HHS/United States ; P20-GM103423/GM/NIGMS NIH HHS/United States ; P20-GM104318/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Cell Proliferation ; Chromatin/metabolism ; *Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; *Regulatory Elements, Transcriptional ; }, abstract = {It is proposed that the evolution of complex animals required repressive genetic mechanisms for controlling the transcriptional and proliferative potency of cells. Unicellular organisms are transcriptionally potent, able to express their full genetic complement as the need arises through their life cycle, whereas differentiated cells of multicellular organisms can only express a fraction of their genomic potential. Likewise, whereas cell proliferation in unicellular organisms is primarily limited by nutrient availability, cell proliferation in multicellular organisms is developmentally regulated. Repressive genetic controls limiting the potency of cells at the end of ontogeny would have stabilized the gene expression states of differentiated cells and prevented disruptive proliferation, allowing the emergence of diverse cell types and functional shapes. We propose that distal cis-regulatory elements represent the primary innovations that set the stage for the evolution of developmental gene regulatory networks and the repressive control of key multipotency and cell-cycle control genes. The testable prediction of this model is that the genomes of extant animals, unlike those of our unicellular relatives, encode gene regulatory circuits dedicated to the developmental control of transcriptional and proliferative potency.}, } @article {pmid26163933, year = {2015}, author = {Bridier, A and Hammes, F and Canette, A and Bouchez, T and Briandet, R}, title = {Fluorescence-based tools for single-cell approaches in food microbiology.}, journal = {International journal of food microbiology}, volume = {213}, number = {}, pages = {2-16}, doi = {10.1016/j.ijfoodmicro.2015.07.003}, pmid = {26163933}, issn = {1879-3460}, mesh = {Bacteria/growth & development ; Flow Cytometry ; Fluorescence ; Food Microbiology/*methods ; Lab-On-A-Chip Devices ; Microbial Consortia/physiology ; Optical Imaging/*methods ; Single-Cell Analysis/*methods ; }, abstract = {The better understanding of the functioning of microbial communities is a challenging and crucial issue in the field of food microbiology, as it constitutes a prerequisite to the optimization of positive and technological microbial population functioning, as well as for the better control of pathogen contamination of food. Heterogeneity appears now as an intrinsic and multi-origin feature of microbial populations and is a major determinant of their beneficial or detrimental functional properties. The understanding of the molecular and cellular mechanisms behind the behavior of bacteria in microbial communities requires therefore observations at the single-cell level in order to overcome "averaging" effects inherent to traditional global approaches. Recent advances in the development of fluorescence-based approaches dedicated to single-cell analysis provide the opportunity to study microbial communities with an unprecedented level of resolution and to obtain detailed insights on the cell structure, metabolism activity, multicellular behavior and bacterial interactions in complex communities. These methods are now increasingly applied in the field of food microbiology in different areas ranging from research laboratories to industry. In this perspective, we reviewed the main fluorescence-based tools used for single-cell approaches and their concrete applications with specific focus on food microbiology.}, } @article {pmid26159581, year = {2016}, author = {Rosa, TM and Giovanna, PM and Maria, M and Angela, M and Matteo, C}, title = {Old Weapons for New Wars: Bioactive Molecules From Cnidarian Internal Defense Systems.}, journal = {Central nervous system agents in medicinal chemistry}, volume = {16}, number = {3}, pages = {183-196}, doi = {10.2174/1871524915666150710120650}, pmid = {26159581}, issn = {1875-6166}, mesh = {Animals ; Anti-Infective Agents/immunology/isolation & purification/toxicity ; *Cnidaria ; Cnidarian Venoms/immunology/isolation & purification/*toxicity ; Humans ; Neurotoxins/immunology/isolation & purification/*toxicity ; Peptides/immunology/isolation & purification/*toxicity ; Sodium Channel Blockers/immunology/isolation & purification/toxicity ; }, abstract = {The renewed interest in the study of genes of immunity in Cnidaria has led to additional information to the scenario of the first stages of immunity evolution revealing the cellular processes involved in symbiosis, in the regulation of homeostasis and in the fight against infections. The recent study with new molecular and functional approach on these organisms have therefore contributed with unexpected information on the knowledge of the stages of capturing activities and defense mechanisms strongly associated with toxin production. Cnidarians are diblastic aquatic animals with radial symmetry; they represent the ancestral state of Metazoa, they are the simplest multicellular organisms that have reached the level of tissue organization.The Cnidaria phylum has evolved using biotoxins as defense or predation mechanisms for ensure survival in hostile and competitive environments such as the seas and oceans. From benthic and pelagic species a large number of toxic compounds that have been determined can have an active role in the development of various antiviral, anticancer and antibacterial functions. Although the immune defense response of these animals is scarcely known, the tissues and the mucus produced by cnidarians are involved in immune defense and contain a large variety of peptides such as sodium and potassium channel neurotoxins, cytolysins, phospholipase A2 (PLA2), acid-sensing ion channel peptide toxins (ASICs) and other toxins, classified following biochemical and pharmacological studies on the basis of functional, molecular and structural parameters. These basal metazoan in fact, are far from "simple" in the range of methods at their disposal to deal with potential prey but also invading microbes and pathogens. They could also take advantage of the multi-functionality of some of their toxins, for example, some bioactive molecules have characteristics of toxicity associated with a potential antimicrobial activity. The interest in cnidarians was not only directed to the study of toxins and venom, but also to the fact these animals have been suggested as source of new molecules potentially relevant for biotechnology and pharmaceutical applications. Here, we review the cnidarian type of toxins regarding their multifunctional role and the future possibility of drawing important applications in fields ranging from biology to pharmacology.}, } @article {pmid26157427, year = {2015}, author = {Mora Van Cauwelaert, E and Arias Del Angel, JA and Benítez, M and Azpeitia, EM}, title = {Development of cell differentiation in the transition to multicellularity: a dynamical modeling approach.}, journal = {Frontiers in microbiology}, volume = {6}, number = {}, pages = {603}, pmid = {26157427}, issn = {1664-302X}, abstract = {Multicellularity has emerged and continues to emerge in a variety of lineages and under diverse environmental conditions. In order to attain individuality and integration, multicellular organisms must exhibit spatial cell differentiation, which in turn allows cell aggregates to robustly generate traits and behaviors at the multicellular level. Nevertheless, the mechanisms that may lead to the development of cellular differentiation and patterning in emerging multicellular organisms remain unclear. We briefly review two conceptual frameworks that have addressed this issue: the cooperation-defection framework and the dynamical patterning modules (DPMs) framework. Then, situating ourselves in the DPM formalism first put forward by S. A. Newman and collaborators, we state a hypothesis for cell differentiation and arrangement in cellular masses of emerging multicellular organisms. Our hypothesis is based on the role of the generic cell-to-cell communication and adhesion patterning mechanisms, which are two fundamental mechanisms for the evolution of multicellularity, and whose molecules seem to be well-conserved in extant multicellular organisms and their unicellular relatives. We review some fundamental ideas underlying this hypothesis and contrast them with empirical and theoretical evidence currently available. Next, we use a mathematical model to illustrate how the mechanisms and assumptions considered in the hypothesis we postulate may render stereotypical arrangements of differentiated cells in an emerging cellular aggregate and may contribute to the variation and recreation of multicellular phenotypes. Finally, we discuss the potential implications of our approach and compare them to those entailed by the cooperation-defection framework in the study of cell differentiation in the transition to multicellularity.}, } @article {pmid26156204, year = {2015}, author = {Niklas, KJ and Kutschera, U}, title = {Kleiber's Law: How the Fire of Life ignited debate, fueled theory, and neglected plants as model organisms.}, journal = {Plant signaling & behavior}, volume = {10}, number = {7}, pages = {e1036216}, pmid = {26156204}, issn = {1559-2324}, mesh = {Animals ; Autotrophic Processes ; Cell Respiration ; Metabolism ; *Models, Biological ; Phototrophic Processes ; Plants/*metabolism ; }, abstract = {Size is a key feature of any organism since it influences the rate at which resources are consumed and thus affects metabolic rates. In the 1930s, size-dependent relationships were codified as "allometry" and it was shown that most of these could be quantified using the slopes of log-log plots of any 2 variables of interest. During the decades that followed, physiologists explored how animal respiration rates varied as a function of body size across taxa. The expectation was that rates would scale as the 2/3 power of body size as a reflection of the Euclidean relationship between surface area and volume. However, the work of Max Kleiber (1893-1976) and others revealed that animal respiration rates apparently scale more closely as the 3/4 power of body size. This phenomenology, which is called "Kleiber's Law," has been described for a broad range of organisms, including some algae and plants. It has also been severely criticized on theoretical and empirical grounds. Here, we review the history of the analysis of metabolism, which originated with the works of Antoine L. Lavoisier (1743-1794) and Julius Sachs (1832-1897), and culminated in Kleiber's book The Fire of Life (1961; 2. ed. 1975). We then evaluate some of the criticisms that have been leveled against Kleiber's Law and some examples of the theories that have tried to explain it. We revive the speculation that intracellular exo- and endocytotic processes are resource delivery-systems, analogous to the supercellular systems in multicellular organisms. Finally, we present data that cast doubt on the existence of a single scaling relationship between growth and body size in plants.}, } @article {pmid26156140, year = {2015}, author = {Wallace-Salinas, V and Brink, DP and Ahrén, D and Gorwa-Grauslund, MF}, title = {Cell periphery-related proteins as major genomic targets behind the adaptive evolution of an industrial Saccharomyces cerevisiae strain to combined heat and hydrolysate stress.}, journal = {BMC genomics}, volume = {16}, number = {1}, pages = {514}, pmid = {26156140}, issn = {1471-2164}, mesh = {Biological Evolution ; Ethanol/metabolism ; Genomics/*methods ; Hot Temperature ; Industrial Microbiology ; *Mutation ; Saccharomyces cerevisiae/genetics/*growth & development/metabolism ; Saccharomyces cerevisiae Proteins/*genetics/metabolism ; Selection, Genetic ; Sequence Analysis, DNA ; Stress, Physiological ; }, abstract = {BACKGROUND: Laboratory evolution is an important tool for developing robust yeast strains for bioethanol production since the biological basis behind combined tolerance requires complex alterations whose proper regulation is difficult to achieve by rational metabolic engineering. Previously, we reported on the evolved industrial Saccharomyces cerevisiae strain ISO12 that had acquired improved tolerance to grow and ferment in the presence of lignocellulose-derived inhibitors at high temperature (39 °C). In the current study, we used comparative genomics to uncover the extent of the genomic alterations that occurred during the evolution process and investigated possible associations between the mutations and the phenotypic traits in ISO12.

RESULTS: Through whole-genome sequencing and variant calling we identified a high number of strain-unique SNPs and INDELs in both ISO12 and the parental strain Ethanol Red. The variants were predicted to have 760 non-synonymous effects in both strains combined and were significantly enriched in Gene Ontology terms related to cell periphery, membranes and cell wall. Eleven genes, including MTL1, FLO9/FLO11, and CYC3 were found to be under positive selection in ISO12. Additionally, the FLO genes exhibited changes in copy number, and the alterations to this gene family were correlated with experimental results of multicellularity and invasive growth in the adapted strain. An independent lipidomic analysis revealed further differences between the strains in the content of nine lipid species. Finally, ISO12 displayed improved viability in undiluted spruce hydrolysate that was unrelated to reduction of inhibitors and changes in cell wall integrity, as shown by HPLC and lyticase assays.

CONCLUSIONS: Together, the results of the sequence comparison and the physiological characterisations indicate that cell-periphery proteins (e.g. extracellular sensors such as MTL1) and peripheral lipids/membranes are important evolutionary targets in the process of adaptation to the combined stresses. The capacity of ISO12 to develop complex colony formation also revealed multicellularity as a possible evolutionary strategy to improve competitiveness and tolerance to environmental stresses (also reflected by the FLO genes). Although a panel of altered genes with high relevance to the novel phenotype was detected, this study also demonstrates that the observed long-term molecular effects of thermal and inhibitor stress have polygenetic basis.}, } @article {pmid26150498, year = {2015}, author = {Rendueles, O and Zee, PC and Dinkelacker, I and Amherd, M and Wielgoss, S and Velicer, GJ}, title = {Rapid and widespread de novo evolution of kin discrimination.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {29}, pages = {9076-9081}, pmid = {26150498}, issn = {1091-6490}, support = {R01 GM079690/GM/NIGMS NIH HHS/United States ; GM079690/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; *Biological Evolution ; Chimera ; Myxococcus xanthus/genetics/isolation & purification/*physiology ; Phenotype ; Time Factors ; }, abstract = {Diverse forms of kin discrimination, broadly defined as alteration of social behavior as a function of genetic relatedness among interactants, are common among social organisms from microbes to humans. However, the evolutionary origins and causes of kin-discriminatory behavior remain largely obscure. One form of kin discrimination observed in microbes is the failure of genetically distinct colonies to merge freely upon encounter. Here, we first use natural isolates of the highly social bacterium Myxococcus xanthus to show that colony-merger incompatibilities can be strong barriers to social interaction, particularly by reducing chimerism in multicellular fruiting bodies that develop near colony-territory borders. We then use experimental laboratory populations to test hypotheses regarding the evolutionary origins of kin discrimination. We show that the generic process of adaptation, irrespective of selective environment, is sufficient to repeatedly generate kin-discriminatory behaviors between evolved populations and their common ancestor. Further, we find that kin discrimination pervasively evolves indirectly between allopatric replicate populations that adapt to the same ecological habitat and that this occurs generically in many distinct habitats. Patterns of interpopulation discrimination imply that kin discrimination phenotypes evolved via many diverse genetic mechanisms and mutation-accumulation patterns support this inference. Strong incompatibility phenotypes emerged abruptly in some populations but strengthened gradually in others. The indirect evolution of kin discrimination in an asexual microbe is analogous to the indirect evolution of reproductive incompatibility in sexual eukaryotes and linguistic incompatibility among human cultures, the commonality being indirect, noncoordinated divergence of complex systems evolving in isolation.}, } @article {pmid26141828, year = {2016}, author = {Gu, X}, title = {Understanding tissue expression evolution: from expression phylogeny to phylogenetic network.}, journal = {Briefings in bioinformatics}, volume = {17}, number = {2}, pages = {249-254}, doi = {10.1093/bib/bbv041}, pmid = {26141828}, issn = {1477-4054}, mesh = {Animals ; *Evolution, Molecular ; Gene Expression Profiling/*methods ; Gene Expression Regulation/*genetics ; Gene Regulatory Networks/*genetics ; Humans ; Phylogeny ; Transcriptome/*genetics ; Viscera/*physiology ; }, abstract = {Our understanding of tissue expression evolution in multi-cellular model organisms has been considerably advanced with the help of high-throughput technologies from EST, microarray to RNA-seq. Yet, many controversies remained unsolved, ranging from the evolutionary patterns of tissue expressions to expression phylogenetic analysis. Moreover, despite numerous reports published, it is desirable to have a general framework for study of tissue expression evolution. In this article, we first provide an up-to-date and concise review for the study of tissue expression evolution in multi-cellular organisms. While the expression phylogeny of the same tissues sampled from closely or intermediately related species largely reflects the species phylogeny, we demonstrate that phylogenetic network approach may shed some lights for our understanding of the developmental similarity and evolutionary relatedness during the multi-tissue evolution.}, } @article {pmid26136819, year = {2015}, author = {Ducasse, H and Arnal, A and Vittecoq, M and Daoust, SP and Ujvari, B and Jacqueline, C and Tissot, T and Ewald, P and Gatenby, RA and King, KC and Bonhomme, F and Brodeur, J and Renaud, F and Solary, E and Roche, B and Thomas, F}, title = {Cancer: an emergent property of disturbed resource-rich environments? Ecology meets personalized medicine.}, journal = {Evolutionary applications}, volume = {8}, number = {6}, pages = {527-540}, pmid = {26136819}, issn = {1752-4571}, abstract = {For an increasing number of biologists, cancer is viewed as a dynamic system governed by evolutionary and ecological principles. Throughout most of human history, cancer was an uncommon cause of death and it is generally accepted that common components of modern culture, including increased physiological stresses and caloric intake, favor cancer development. However, the precise mechanisms for this linkage are not well understood. Here, we examine the roles of ecological and physiological disturbances and resource availability on the emergence of cancer in multicellular organisms. We argue that proliferation of 'profiteering phenotypes' is often an emergent property of disturbed, resource-rich environments at all scales of biological organization. We review the evidence for this phenomenon, explore it within the context of malignancy, and discuss how this ecological framework may offer a theoretical background for novel strategies of cancer prevention. This work provides a compelling argument that the traditional separation between medicine and evolutionary ecology remains a fundamental limitation that needs to be overcome if complex processes, such as oncogenesis, are to be completely understood.}, } @article {pmid26131935, year = {2015}, author = {Gavelis, GS and Hayakawa, S and White, RA and Gojobori, T and Suttle, CA and Keeling, PJ and Leander, BS}, title = {Eye-like ocelloids are built from different endosymbiotically acquired components.}, journal = {Nature}, volume = {523}, number = {7559}, pages = {204-207}, pmid = {26131935}, issn = {1476-4687}, mesh = {Dinoflagellida/*genetics/physiology/*ultrastructure ; Genome, Protozoan/genetics ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Mitochondria/metabolism/ultrastructure ; Molecular Sequence Data ; Plastids/metabolism/ultrastructure ; Protozoan Proteins/genetics ; Rhodophyta/genetics ; *Symbiosis ; }, abstract = {Multicellularity is often considered a prerequisite for morphological complexity, as seen in the camera-type eyes found in several groups of animals. A notable exception exists in single-celled eukaryotes called dinoflagellates, some of which have an eye-like 'ocelloid' consisting of subcellular analogues to a cornea, lens, iris, and retina. These planktonic cells are uncultivated and rarely encountered in environmental samples, obscuring the function and evolutionary origin of the ocelloid. Here we show, using a combination of electron microscopy, tomography, isolated-organelle genomics, and single-cell genomics, that ocelloids are built from pre-existing organelles, including a cornea-like layer made of mitochondria and a retinal body made of anastomosing plastids. We find that the retinal body forms the central core of a network of peridinin-type plastids, which in dinoflagellates and their relatives originated through an ancient endosymbiosis with a red alga. As such, the ocelloid is a chimaeric structure, incorporating organelles with different endosymbiotic histories. The anatomical complexity of single-celled organisms may be limited by the components available for differentiation, but the ocelloid shows that pre-existing organelles can be assembled into a structure so complex that it was initially mistaken for a multicellular eye. Although mitochondria and plastids are acknowledged chiefly for their metabolic roles, they can also be building blocks for greater structural complexity.}, } @article {pmid26124052, year = {2015}, author = {Tomic, B and Kusic-Tisma, J}, title = {HsOrc4-Dependent Dna Remodeling of the ori-β Dhfr Replicator.}, journal = {Cellular & molecular biology letters}, volume = {20}, number = {4}, pages = {549-561}, doi = {10.1515/cmble-2015-0032}, pmid = {26124052}, issn = {1689-1392}, mesh = {AT Rich Sequence ; Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Binding Sites ; Cell Cycle Proteins/chemistry/genetics/*metabolism ; Cricetulus ; DNA Replication ; DNA-Binding Proteins ; *Nucleic Acid Conformation ; Origin Recognition Complex/chemistry/genetics/*metabolism ; Plant Proteins/chemistry/metabolism ; Plasmids/chemistry/genetics ; RNA-Binding Proteins ; *Replication Origin ; Single-Strand Specific DNA and RNA Endonucleases/chemistry/metabolism ; Tetrahydrofolate Dehydrogenase/*genetics ; }, abstract = {Replication of DNA in multicellular organisms initiates from origin of replication (ori) sequences, which significantly differ in length and complexity. One of the best characterized is hamster dihydrofolate reductase (DHFR), which contains the ori-β sequence with several functionally relevant domains, such as an AT-rich region, dinucleotide repeat element (DNR), sequence-induced bend DNA (BEND) and a RIP60 protein-binding site (RIP60). Prior to initiation, ori sequences are recognized by origin recognition complex (ORC), which is a hetero hexamer complex that serves as the landing pad for proteins of the pre-replication complex. The function of each ORC subunit is still unclear. In this study, we analyze the function of subunit 4 of the human ORC complex (HsOrc4) in interaction with a plasmid bearing the ori-β DHFR sequence. We show that the topologically closed DHFR ori-β replicator contains a bubble-like structure within its AT-rich region and that it is reversibly modified in the interaction with HsOrc4. The non-canonical structure of the AT-rich region in the topologically closed ori sequence is recognized and changed by HsOrc4 using the energy of supercoiled DNA. These findings could help to further elucidate DNA replication and its possible association with human genetic diseases.}, } @article {pmid26124000, year = {2015}, author = {Schwessinger, B and Rathjen, JP}, title = {Changing SERKs and priorities during plant life.}, journal = {Trends in plant science}, volume = {20}, number = {9}, pages = {531-533}, doi = {10.1016/j.tplants.2015.06.006}, pmid = {26124000}, issn = {1878-4372}, mesh = {Biological Evolution ; *Gene Expression Regulation, Plant ; Magnoliopsida/*genetics/metabolism ; Plant Proteins/*genetics/metabolism ; Protein Kinases/*genetics/metabolism ; *Signal Transduction ; }, abstract = {SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASES (SERKs) are coreceptors for diverse extracellular signals. SERKs are involved in a wide array of developmental and immune related processes first discovered in Arabidopsis. Recent work demonstrates the evolutionary conservation of SERKs in all multicellular plants, and highlights their functional conservation in monocots and dicots.}, } @article {pmid26121931, year = {2016}, author = {Mishra, RC and Grover, A}, title = {ClpB/Hsp100 proteins and heat stress tolerance in plants.}, journal = {Critical reviews in biotechnology}, volume = {36}, number = {5}, pages = {862-874}, doi = {10.3109/07388551.2015.1051942}, pmid = {26121931}, issn = {1549-7801}, mesh = {Endopeptidase Clp/*genetics ; Global Warming ; Heat-Shock Proteins/*genetics ; Molecular Chaperones ; Mutation ; Phylogeny ; Plants, Genetically Modified/*genetics ; Stress, Physiological/genetics ; Thermotolerance/*genetics ; }, abstract = {High-temperature stress can disrupt cellular proteostasis, resulting in the accumulation of insoluble protein aggregates. For survival under stressful conditions, it is important for cells to maintain a pool of native soluble proteins by preventing and/or dissociating these aggregates. Chaperones such as GroEL/GroES (Hsp60/Hsp10) and DnaK/DnaJ/GrpE (Hsp70/Hsp40/nucleotide exchange factor) help cells minimize protein aggregation. Protein disaggregation is accomplished by chaperones belonging to the Caseinolytic Protease (Clp) family of proteins. ClpB/Hsp100 proteins are strikingly ubiquitous and are found in bacteria, yeast and multi-cellular plants. The expression of these proteins is regulated by heat stress (HS) and developmental cues. Bacteria and yeast contain one and two forms of ClpB proteins, respectively. Plants possess multiple forms of these proteins that are localized to different cellular compartments (i.e. cytoplasm/nucleus, chloroplast or mitochondria). Overwhelming evidence suggests that ClpB/Hsp100 proteins play decisive roles in cell adaptation to HS. Mutant bacteria and yeast cells lacking active ClpB/Hsp100 proteins are critically sensitive to high-temperature stress. Likewise, Arabidopsis, maize and rice mutants lacking cytoplasmic ClpB proteins are very sensitive to heat. In this study, we present the structural and functional attributes of plant ClpB forms.}, } @article {pmid26116678, year = {2015}, author = {Risgaard-Petersen, N and Kristiansen, M and Frederiksen, RB and Dittmer, AL and Bjerg, JT and Trojan, D and Schreiber, L and Damgaard, LR and Schramm, A and Nielsen, LP}, title = {Cable Bacteria in Freshwater Sediments.}, journal = {Applied and environmental microbiology}, volume = {81}, number = {17}, pages = {6003-6011}, pmid = {26116678}, issn = {1098-5336}, support = {291650/ERC_/European Research Council/International ; }, mesh = {Deltaproteobacteria/*chemistry/classification/genetics/metabolism ; Electricity ; Electron Transport ; Fresh Water/*microbiology ; Geologic Sediments/*microbiology ; Molecular Sequence Data ; Oxidation-Reduction ; Oxygen/metabolism ; Phylogeny ; Sulfides/metabolism ; }, abstract = {In marine sediments cathodic oxygen reduction at the sediment surface can be coupled to anodic sulfide oxidation in deeper anoxic layers through electrical currents mediated by filamentous, multicellular bacteria of the Desulfobulbaceae family, the so-called cable bacteria. Until now, cable bacteria have only been reported from marine environments. In this study, we demonstrate that cable bacteria also occur in freshwater sediments. In a first step, homogenized sediment collected from the freshwater stream Giber Å, Denmark, was incubated in the laboratory. After 2 weeks, pH signatures and electric fields indicated electron transfer between vertically separated anodic and cathodic half-reactions. Fluorescence in situ hybridization revealed the presence of Desulfobulbaceae filaments. In addition, in situ measurements of oxygen, pH, and electric potential distributions in the waterlogged banks of Giber Å demonstrated the presence of distant electric redox coupling in naturally occurring freshwater sediment. At the same site, filamentous Desulfobulbaceae with cable bacterium morphology were found to be present. Their 16S rRNA gene sequence placed them as a distinct sister group to the known marine cable bacteria, with the genus Desulfobulbus as the closest cultured lineage. The results of the present study indicate that electric currents mediated by cable bacteria could be important for the biogeochemistry in many more environments than anticipated thus far and suggest a common evolutionary origin of the cable phenotype within Desulfobulbaceae with subsequent diversification into a freshwater and a marine lineage.}, } @article {pmid26116421, year = {2016}, author = {Ishizaki, K and Nishihama, R and Yamato, KT and Kohchi, T}, title = {Molecular Genetic Tools and Techniques for Marchantia polymorpha Research.}, journal = {Plant & cell physiology}, volume = {57}, number = {2}, pages = {262-270}, doi = {10.1093/pcp/pcv097}, pmid = {26116421}, issn = {1471-9053}, mesh = {Crosses, Genetic ; Marchantia/*genetics ; Molecular Biology/*methods ; Plastids/genetics ; *Research ; Transformation, Genetic ; }, abstract = {Liverworts occupy a basal position in the evolution of land plants, and are a key group to address a wide variety of questions in plant biology. Marchantia polymorpha is a common, easily cultivated, dioecious liverwort species, and is emerging as an experimental model organism. The haploid gametophytic generation dominates the diploid sporophytic generation in its life cycle. Genetically homogeneous lines in the gametophyte generation can be established easily and propagated through asexual reproduction, which aids genetic and biochemical experiments. Owing to its dioecy, male and female sexual organs are formed in separate individuals, which enables crossing in a fully controlled manner. Reproductive growth can be induced at the desired times under laboratory conditions, which helps genetic analysis. The developmental process from a single-celled spore to a multicellular body can be observed directly in detail. As a model organism, molecular techniques for M. polymorpha are well developed; for example, simple and efficient protocols of Agrobacterium-mediated transformation have been established. Based on them, various strategies for molecular genetics, such as introduction of reporter constructs, overexpression, gene silencing and targeted gene modification, are available. Herein, we describe the technologies and resources for reverse and forward genetics in M. polymorpha, which offer an excellent experimental platform to study the evolution and diversity of regulatory systems in land plants.}, } @article {pmid26106978, year = {2015}, author = {Zielezinski, A and Karlowski, WM}, title = {Early origin and adaptive evolution of the GW182 protein family, the key component of RNA silencing in animals.}, journal = {RNA biology}, volume = {12}, number = {7}, pages = {761-770}, pmid = {26106978}, issn = {1555-8584}, mesh = {Animals ; Autoantigens/genetics/*metabolism ; *Evolution, Molecular ; Humans ; Invertebrates/genetics/metabolism ; *RNA Interference ; RNA-Binding Proteins/genetics/*metabolism ; Vertebrates/genetics/metabolism ; }, abstract = {The GW182 proteins are a key component of the miRNA-dependent post-transcriptional silencing pathway in animals. They function as scaffold proteins to mediate the interaction of Argonaute (AGO)-containing complexes with cytoplasmic poly(A)-binding proteins (PABP) and PAN2-PAN3 and CCR4-NOT deadenylases. The AGO-GW182 complexes mediate silencing of the target mRNA through induction of translational repression and/or mRNA degradation. Although the GW182 proteins are a subject of extensive experimental research in the recent years, very little is known about their origin and evolution. Here, based on complex functional annotation and phylogenetic analyses, we reveal 448 members of the GW182 protein family from the earliest animals to humans. Our results indicate that a single-copy GW182/TNRC6C progenitor gene arose with the emergence of multicellularity and it multiplied in the last common ancestor of vertebrates in 2 rounds of whole genome duplication (WGD) resulting in 3 genes. Before the divergence of vertebrates, both the AGO- and CCR4-NOT-binding regions of GW182s showed significant acceleration in the accumulation of amino acid changes, suggesting functional adaptation toward higher specificity to the molecules of the silencing complex. We conclude that the silencing ability of the GW182 proteins improves with higher position in the taxonomic classification and increasing complexity of the organism. The first reconstruction of the molecular journey of GW182 proteins from the ancestral metazoan protein to the current mammalian configuration provides new insight into development of the miRNA-dependent post-transcriptional silencing pathway in animals.}, } @article {pmid26105654, year = {2015}, author = {Koeduka, T and Ishizaki, K and Mwenda, CM and Hori, K and Sasaki-Sekimoto, Y and Ohta, H and Kohchi, T and Matsui, K}, title = {Biochemical characterization of allene oxide synthases from the liverwort Marchantia polymorpha and green microalgae Klebsormidium flaccidum provides insight into the evolutionary divergence of the plant CYP74 family.}, journal = {Planta}, volume = {242}, number = {5}, pages = {1175-1186}, pmid = {26105654}, issn = {1432-2048}, mesh = {Cytochrome P-450 Enzyme System/genetics/*metabolism ; *Evolution, Molecular ; Intramolecular Oxidoreductases/genetics/*metabolism ; Marchantia/*enzymology ; Microalgae/*enzymology ; Plant Proteins/genetics/*metabolism ; }, abstract = {Allene oxide synthases (AOSs) were isolated from liverworts and charophytes. These AOSs exhibited enzymatic properties similar to those of angiosperms but formed a distinct phylogenetic clade. Allene oxide synthase (AOS) and hydroperoxide lyase (HPL) mediate the formation of precursors of jasmonates and carbon-six volatiles, respectively. AOS and HPL utilize fatty acid hydroperoxides and belong to the plant cytochrome P450 74 (CYP74) family that mediates plant defense against herbivores, pathogens, or abiotic stresses. Although members of the CYP74 family have been reported in mosses and other species, the evolution and function of multiple CYP74 genes in plants remain elusive. Here, we show that the liverwort Marchantia polymorpha belongs to a basal group in the evolution of land plants; has two closely related proteins (59% identity), MpAOS1 and MpAOS2, that are similar to moss PpAOS1 (49 and 47% identity, respectively); and exhibits AOS activity but not HPL activity. We also found that the green microalgae Klebsormidium flaccidum, consist of multicellular and non-branching filaments, contains an enzyme, KfAOS, that is similar to PpAOS1 (37% identity), and converts 13-hydroperoxide of linolenic acid to 12-oxo-phytodienoic acid in a coupled reaction with allene oxide cyclase. Phylogenetic analysis showed two evolutionarily distinct clusters. One cluster comprised AOS and HPL from charophytic algae, liverworts, and mosses, including MpAOSs and KfAOS. The other cluster was formed by angiosperm CYP74. Our results suggest that plant CYP74 enzymes with AOS, HPL, and divinyl ether synthase activities have arisen multiple times and in the two different clades, which occurred prior to the divergence of the flowering plant lineage.}, } @article {pmid26104193, year = {2014}, author = {Goessweiner-Mohr, N and Arends, K and Keller, W and Grohmann, E}, title = {Conjugation in Gram-Positive Bacteria.}, journal = {Microbiology spectrum}, volume = {2}, number = {4}, pages = {PLAS-0004-2013}, doi = {10.1128/microbiolspec.PLAS-0004-2013}, pmid = {26104193}, issn = {2165-0497}, mesh = {*Conjugation, Genetic ; DNA, Bacterial/genetics/metabolism ; Gene Transfer, Horizontal ; Genes, Bacterial ; Gram-Positive Bacteria/*genetics/physiology ; Macromolecular Substances/metabolism ; Membrane Transport Proteins/genetics/metabolism ; Operon ; Type IV Secretion Systems/genetics/metabolism ; }, abstract = {Conjugative transfer is the most important means of spreading antibiotic resistance and virulence factors among bacteria. The key vehicles of this horizontal gene transfer are a group of mobile genetic elements, termed conjugative plasmids. Conjugative plasmids contain as minimum instrumentation an origin of transfer (oriT), DNA-processing factors (a relaxase and accessory proteins), as well as proteins that constitute the trans-envelope transport channel, the so-called mating pair formation (Mpf) proteins. All these protein factors are encoded by one or more transfer (tra) operons that together form the DNA transport machinery, the Gram-positive type IV secretion system. However, multicellular Gram-positive bacteria belonging to the streptomycetes appear to have evolved another mechanism for conjugative plasmid spread reminiscent of the machinery involved in bacterial cell division and sporulation, which transports double-stranded DNA from donor to recipient cells. Here, we focus on the protein key players involved in the plasmid spread through the two different modes and present a new secondary structure homology-based classification system for type IV secretion protein families. Moreover, we discuss the relevance of conjugative plasmid transfer in the environment and summarize novel techniques to visualize and quantify conjugative transfer in situ.}, } @article {pmid26101255, year = {2015}, author = {Tarver, JE and Cormier, A and Pinzón, N and Taylor, RS and Carré, W and Strittmatter, M and Seitz, H and Coelho, SM and Cock, JM}, title = {microRNAs and the evolution of complex multicellularity: identification of a large, diverse complement of microRNAs in the brown alga Ectocarpus.}, journal = {Nucleic acids research}, volume = {43}, number = {13}, pages = {6384-6398}, pmid = {26101255}, issn = {1362-4962}, mesh = {*Evolution, Molecular ; Genetic Loci ; Genetic Variation ; Genome ; MicroRNAs/chemistry/classification/*genetics/metabolism ; Phaeophyta/*genetics/metabolism ; Polymerase Chain Reaction ; Sequence Analysis, RNA ; }, abstract = {There is currently convincing evidence that microRNAs have evolved independently in at least six different eukaryotic lineages: animals, land plants, chlorophyte green algae, demosponges, slime molds and brown algae. MicroRNAs from different lineages are not homologous but some structural features are strongly conserved across the eukaryotic tree allowing the application of stringent criteria to identify novel microRNA loci. A large set of 63 microRNA families was identified in the brown alga Ectocarpus based on mapping of RNA-seq data and nine microRNAs were confirmed by northern blotting. The Ectocarpus microRNAs are highly diverse at the sequence level with few multi-gene families, and do not tend to occur in clusters but exhibit some highly conserved structural features such as the presence of a uracil at the first residue. No homologues of Ectocarpus microRNAs were found in other stramenopile genomes indicating that they emerged late in stramenopile evolution and are perhaps specific to the brown algae. The large number of microRNA loci in Ectocarpus is consistent with the developmental complexity of many brown algal species and supports a proposed link between the emergence and expansion of microRNA regulatory systems and the evolution of complex multicellularity.}, } @article {pmid26100885, year = {2015}, author = {Skippington, E and Barkman, TJ and Rice, DW and Palmer, JD}, title = {Miniaturized mitogenome of the parasitic plant Viscum scurruloideum is extremely divergent and dynamic and has lost all nad genes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {27}, pages = {E3515-24}, pmid = {26100885}, issn = {1091-6490}, mesh = {Base Sequence ; DNA, Mitochondrial/classification/*genetics ; Electron Transport Complex I/*genetics ; Genes, Mitochondrial/genetics ; Genetic Variation ; Genome, Mitochondrial/*genetics ; Mitochondrial Proteins/genetics ; Molecular Sequence Data ; Phylogeny ; Plant Proteins/*genetics ; RNA, Plant/genetics ; RNA, Ribosomal/genetics ; Sequence Homology, Nucleic Acid ; Viscum/*genetics ; }, abstract = {Despite the enormous diversity among parasitic angiosperms in form and structure, life-history strategies, and plastid genomes, little is known about the diversity of their mitogenomes. We report the sequence of the wonderfully bizarre mitogenome of the hemiparasitic aerial mistletoe Viscum scurruloideum. This genome is only 66 kb in size, making it the smallest known angiosperm mitogenome by a factor of more than three and the smallest land plant mitogenome. Accompanying this size reduction is exceptional reduction of gene content. Much of this reduction arises from the unexpected loss of respiratory complex I (NADH dehydrogenase), universally present in all 300+ other angiosperms examined, where it is encoded by nine mitochondrial and many nuclear nad genes. Loss of complex I in a multicellular organism is unprecedented. We explore the potential relationship between this loss in Viscum and its parasitic lifestyle. Despite its small size, the Viscum mitogenome is unusually rich in recombinationally active repeats, possessing unparalleled levels of predicted sublimons resulting from recombination across short repeats. Many mitochondrial gene products exhibit extraordinary levels of divergence in Viscum, indicative of highly relaxed if not positive selection. In addition, all Viscum mitochondrial protein genes have experienced a dramatic acceleration in synonymous substitution rates, consistent with the hypothesis of genomic streamlining in response to a high mutation rate but completely opposite to the pattern seen for the high-rate but enormous mitogenomes of Silene. In sum, the Viscum mitogenome possesses a unique constellation of extremely unusual features, a subset of which may be related to its parasitic lifestyle.}, } @article {pmid26089366, year = {2015}, author = {Kamo, T and Akazawa, H and Komuro, I}, title = {Cardiac nonmyocytes in the hub of cardiac hypertrophy.}, journal = {Circulation research}, volume = {117}, number = {1}, pages = {89-98}, doi = {10.1161/CIRCRESAHA.117.305349}, pmid = {26089366}, issn = {1524-4571}, mesh = {Animals ; Autocrine Communication ; Blood Cells/pathology ; Cardiomegaly/*pathology ; Cell Lineage ; Endothelial Cells/metabolism/pathology ; Endothelin-1/physiology ; Fibroblasts/metabolism/pathology ; Humans ; Intercellular Signaling Peptides and Proteins/physiology ; Macrophages/physiology ; Mast Cells/physiology ; Mice ; MicroRNAs/physiology ; Myocardium/*pathology ; Myocytes, Cardiac/pathology ; Natriuretic Peptides/physiology ; Paracrine Communication ; }, abstract = {Cardiac hypertrophy is characterized by complex multicellular alterations, such as cardiomyocyte growth, angiogenesis, fibrosis, and inflammation. The heart consists of myocytes and nonmyocytes, such as fibroblasts, vascular cells, and blood cells, and these cells communicate with each other directly or indirectly via a variety of autocrine or paracrine mediators. Accumulating evidence has suggested that nonmyocytes actively participate in the development of cardiac hypertrophy. In this review, recent progress in our understanding of the importance of nonmyocytes as a hub for induction of cardiac hypertrophy is summarized with an emphasis of the contribution of noncontact communication mediated by diffusible factors between cardiomyocytes and nonmyocytes in the heart.}, } @article {pmid26079199, year = {2015}, author = {Scianna, M and Bassino, E and Munaron, L}, title = {A cellular Potts model analyzing differentiated cell behavior during in vivo vascularization of a hypoxic tissue.}, journal = {Computers in biology and medicine}, volume = {63}, number = {}, pages = {143-156}, doi = {10.1016/j.compbiomed.2015.05.020}, pmid = {26079199}, issn = {1879-0534}, mesh = {Animals ; *Cell Differentiation ; Endothelial Cells/*metabolism ; Humans ; *Hypoxia/metabolism/physiopathology ; *Models, Cardiovascular ; *Neovascularization, Physiologic ; Protein Isoforms/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {Angiogenesis, the formation of new blood vessel networks from existing capillary or post-capillary venules, is an intrinsically multiscale process occurring in several physio-pathological conditions. In particular, hypoxic tissue cells activate downstream cascades culminating in the secretion of a wide range of angiogenic factors, including VEGF isoforms. Such diffusive chemicals activate the endothelial cells (ECs) forming the external walls of the nearby vessels that chemotactically migrate toward the hypoxic areas of the tissue as multicellular sprouts. A functional network eventually emerges by further branching and anastomosis processes. We here propose a CPM-based approach reproducing selected features of the angiogenic progression necessary for the reoxygenation of a hypoxic tissue. Our model is able to span the different scale involved in the angiogenic progression as it incorporates reaction-diffusion equations for the description of the evolution of microenvironmental variables in a discrete mesoscopic cellular Potts model (CPM) that reproduces the dynamics of the vascular cells. A key feature of this work is the explicit phenotypic differentiation of the ECs themselves, distinguished in quiescent, stalk and tip. The simulation results allow identifying a set of key mechanisms underlying tissue vascularization. Further, we provide evidence that the nascent pattern is characterized by precise topological properties. Finally, we link abnormal sprouting angiogenesis with alteration in selected cell behavior.}, } @article {pmid26066639, year = {2015}, author = {Peng, M and Aye, TT and Snel, B and van Breukelen, B and Scholten, A and Heck, AJ}, title = {Spatial Organization in Protein Kinase A Signaling Emerged at the Base of Animal Evolution.}, journal = {Journal of proteome research}, volume = {14}, number = {7}, pages = {2976-2987}, doi = {10.1021/acs.jproteome.5b00370}, pmid = {26066639}, issn = {1535-3907}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Catalytic Domain ; Conserved Sequence ; Cyclic AMP-Dependent Protein Kinases/*metabolism ; Molecular Sequence Data ; Phylogeny ; Proteomics ; Sequence Homology, Amino Acid ; *Signal Transduction ; Subcellular Fractions/enzymology ; }, abstract = {In phosphorylation-directed signaling, spatial and temporal control is organized by complex interaction networks that diligently direct kinases toward distinct substrates to fine-tune specificity. How these protein networks originate and evolve into complex regulatory machineries are among the most fascinating research questions in biology. Here, spatiotemporal signaling is investigated by tracing the evolutionary dynamics of each functional domain of cAMP-dependent protein kinase (PKA) and its diverse set of A-kinase anchoring proteins (AKAPs). Homologues of the catalytic (PKA-C) and regulatory (PKA-R) domains of the (PKA-R)2-(PKA-C)2 holoenzyme were found throughout evolution. Most variation was observed in the RIIa of PKA-R, crucial for dimerization and docking to AKAPs. The RIIa domain was not observed in all PKA-R homologues. In the fungi and distinct protist lineages, the RIIa domain emerges within PKA-R, but it displays large sequence variation. These organisms do not harbor homologues of AKAPs, suggesting that efficient docking to direct spatiotemporal PKA activity evolved in multicellular eukaryotes. To test this in silico hypothesis, we experimentally screened organisms with increasing complexity by cAMP-based chemical proteomics to reveal that the occurrence of PKA-AKAP interactions indeed coincided and expanded within vertebrates, suggesting a crucial role for AKAPs in the advent of metazoan multicellularity.}, } @article {pmid26063749, year = {2015}, author = {Maliet, O and Shelton, DE and Michod, RE}, title = {A model for the origin of group reproduction during the evolutionary transition to multicellularity.}, journal = {Biology letters}, volume = {11}, number = {6}, pages = {20150157}, pmid = {26063749}, issn = {1744-957X}, mesh = {*Biological Evolution ; *Models, Biological ; Reproduction ; *Selection, Genetic ; Volvocida/*physiology ; }, abstract = {During the evolution of multicellular organisms, the unit of selection and adaptation, the individual, changes from the single cell to the multicellular group. To become individuals, groups must evolve a group life cycle in which groups reproduce other groups. Investigations into the origin of group reproduction have faced a chicken-and-egg problem: traits related to reproduction at the group level often appear both to be a result of and a prerequisite for natural selection at the group level. With a focus on volvocine algae, we model the basic elements of the cell cycle and show how group reproduction can emerge through the coevolution of a life-history trait with a trait underpinning cell cycle change. Our model explains how events in the cell cycle become reordered to create a group life cycle through continuous change in the cell cycle trait, but only if the cell cycle trait can coevolve with the life-history trait. Explaining the origin of group reproduction helps us understand one of life's most familiar, yet fundamental, aspects-its hierarchical structure.}, } @article {pmid26063660, year = {2015}, author = {Gent, JI and Wang, K and Jiang, J and Dawe, RK}, title = {Stable Patterns of CENH3 Occupancy Through Maize Lineages Containing Genetically Similar Centromeres.}, journal = {Genetics}, volume = {200}, number = {4}, pages = {1105-1116}, pmid = {26063660}, issn = {1943-2631}, mesh = {Centromere/*genetics ; Chromatin Immunoprecipitation ; *Chromosomal Instability ; DNA, Plant/genetics ; Genome, Plant/genetics ; Inbreeding ; Repetitive Sequences, Nucleic Acid/genetics ; Zea mays/*genetics ; }, abstract = {While the approximate chromosomal position of centromeres has been identified in many species, little is known about the dynamics and diversity of centromere positions within species. Multiple lines of evidence indicate that DNA sequence has little or no impact in specifying centromeres in maize and in most multicellular organisms. Given that epigenetically defined boundaries are expected to be dynamic, we hypothesized that centromere positions would change rapidly over time, which would result in a diversity of centromere positions in isolated populations. To test this hypothesis, we used CENP-A/cenH3 (CENH3 in maize) chromatin immunoprecipitation to define centromeres in breeding pedigrees that included the B73 inbred as a common parent. While we found a diversity of CENH3 profiles for centromeres with divergent sequences that were not inherited from B73, the CENH3 profiles from centromeres that were inherited from B73 were indistinguishable from each other. We propose that specific genetic elements in centromeric regions favor or inhibit CENH3 accumulation, leading to reproducible patterns of CENH3 occupancy. These data also indicate that dramatic shifts in centromere position normally originate from accumulated or large-scale genetic changes rather than from epigenetic positional drift.}, } @article {pmid26056368, year = {2015}, author = {Ewald, PW and Swain Ewald, HA}, title = {Infection and cancer in multicellular organisms.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {370}, number = {1673}, pages = {}, pmid = {26056368}, issn = {1471-2970}, mesh = {Animals ; Biological Evolution ; Environmental Pollutants/toxicity ; Humans ; Infections/*complications ; Models, Biological ; Neoplasms/*etiology ; Oncogenic Viruses/pathogenicity ; Tumor Virus Infections/etiology ; }, abstract = {Evolutionary considerations suggest that oncogenic infections should be pervasive among animal species. Infection-associated cancers are well documented in humans and domestic animals, less commonly reported in undomesticated captive animals, and rarely documented in nature. In this paper, we review the literature associating infectious agents with cancer to evaluate the reasons for this pattern. Non-malignant infectious neoplasms occur pervasively in multicellular life, but oncogenic progression to malignancy is often uncertain. Evidence from humans and domestic animals shows that non-malignant infectious neoplasms can develop into cancer, although generally with low frequency. Malignant neoplasms could be difficult to find in nature because of a low frequency of oncogenic transformation, short survival after malignancy and reduced survival prior to malignancy. Moreover, the evaluation of malignancy can be ambiguous in nature, because criteria for malignancy may be difficult to apply consistently across species. The information available in the literature therefore does not allow for a definitive assessment of the pervasiveness of infectious cancers in nature, but the presence of infectious neoplasias and knowledge about the progression of benign neoplasias to cancer is consistent with a widespread but largely undetected occurrence.}, } @article {pmid26056363, year = {2015}, author = {Aktipis, CA and Boddy, AM and Jansen, G and Hibner, U and Hochberg, ME and Maley, CC and Wilkinson, GS}, title = {Cancer across the tree of life: cooperation and cheating in multicellularity.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {370}, number = {1673}, pages = {}, pmid = {26056363}, issn = {1471-2970}, support = {R01 CA185138/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; P01 CA91955/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; BC132057/BC/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Cell Communication ; Cell Differentiation ; Cell Proliferation ; Humans ; Models, Biological ; Neoplasms/etiology/*pathology/physiopathology ; Phylogeny ; Tumor Microenvironment ; }, abstract = {Multicellularity is characterized by cooperation among cells for the development, maintenance and reproduction of the multicellular organism. Cancer can be viewed as cheating within this cooperative multicellular system. Complex multicellularity, and the cooperation underlying it, has evolved independently multiple times. We review the existing literature on cancer and cancer-like phenomena across life, not only focusing on complex multicellularity but also reviewing cancer-like phenomena across the tree of life more broadly. We find that cancer is characterized by a breakdown of the central features of cooperation that characterize multicellularity, including cheating in proliferation inhibition, cell death, division of labour, resource allocation and extracellular environment maintenance (which we term the five foundations of multicellularity). Cheating on division of labour, exhibited by a lack of differentiation and disorganized cell masses, has been observed in all forms of multicellularity. This suggests that deregulation of differentiation is a fundamental and universal aspect of carcinogenesis that may be underappreciated in cancer biology. Understanding cancer as a breakdown of multicellular cooperation provides novel insights into cancer hallmarks and suggests a set of assays and biomarkers that can be applied across species and characterize the fundamental requirements for generating a cancer.}, } @article {pmid26054350, year = {2015}, author = {Olovnikov, AM}, title = {Chronographic theory of development, aging, and origin of cancer: role of chronomeres and printomeres.}, journal = {Current aging science}, volume = {8}, number = {1}, pages = {76-88}, pmid = {26054350}, issn = {1874-6128}, mesh = {*Aging ; Animals ; Humans ; *Neoplasms/genetics ; Polymers/*pharmacology ; Sex Characteristics ; Telomere ; Telomere Shortening ; }, abstract = {It is supposed that the development and aging of multicellular animals and humans are controlled by a special form of the clock mechanism - a chronograph. The development of animals and their aging are interconnected by the program of the species lifespan that has been selected in the evolution of each species to fit the resources of its ecological niche. The theory is based on the idea about a controlled loss by the neurons in the brain of hypothetical organelles - chronomeres that represent themselves small DNA molecules, which are amplificates of the segments of chromosomal DNA. A regular mode of the process of chronomere losses by neurons is provided by a pacemaker localized in the pineal gland and activated at least once per lunar month. Neurons, consecutively losing their chronomeres, are organized in the brain in the temporal relay race. Analogues of chronomeres, namely printomeres, are supposed to exist in dividing non-neuronal cells. Printomeres are not involved in a performance of temporal function, instead they are responsible for the maintenance in dividing cells of their memory about the state of differentiation. A critical shortening or loss of a printomere in a dividing cell leads to a cellular senescence, whereas telomere shortening is a bystander of this process. Thus, aging of a multicellular organism is associated with the loss of chronomeres, whereas senescence of dividing cells is associated with the loss of regulatory RNAs encoded by printomeres. If the cells that have lost their printomeres are environmentally forced to divide, they can transform into cancer cells.}, } @article {pmid26051889, year = {2015}, author = {Rendueles, O and Amherd, M and Velicer, GJ}, title = {Positively Frequency-Dependent Interference Competition Maintains Diversity and Pervades a Natural Population of Cooperative Microbes.}, journal = {Current biology : CB}, volume = {25}, number = {13}, pages = {1673-1681}, doi = {10.1016/j.cub.2015.04.057}, pmid = {26051889}, issn = {1879-0445}, mesh = {Antibiosis/*physiology ; *Biodiversity ; Microbial Interactions/*physiology ; Myxococcus xanthus/*physiology ; Population Density ; Selection, Genetic/*physiology ; Species Specificity ; }, abstract = {Positively frequency-dependent selection is predicted from theory to promote diversity in patchily structured populations and communities, but empirical support for this prediction has been lacking. Here, we investigate frequency-dependent selection among isolates from a local natural population of the highly social bacterium Myxococcus xanthus. Upon starvation, closely related cells of M. xanthus cooperate to construct multicellular fruiting bodies, yet recently diverged genotypes co-residing in a local soil population often antagonize one another during fruiting-body development in mixed groups. In the experiments reported here, both fitness per se and strong forms of interference competition exhibit pervasive and strong positive frequency dependence (PFD) among many isolates from a centimeter-scale soil population of M. xanthus. All strains that compete poorly at intermediate frequency are shown to be competitively dominant at high frequency in most genotype pairings during both growth and development, and strongly so. Interference competition is often lethal and appears to be contact dependent rather than mediated by diffusible compounds. Finally, we experimentally demonstrate that positively frequency-dependent selection maintains diversity when genotype frequencies vary patchily in structured populations. These results suggest that PFD contributes to the high levels of local diversity found among M. xanthus social groups in natural soil populations by reinforcing social barriers to cross-territory invasion and thereby also promotes high within-group relatedness. More broadly, our results suggest that potential roles of PFD in maintaining patchily distributed diversity should be investigated more extensively in other species.}, } @article {pmid26048704, year = {2015}, author = {Sheikh, S and Gloeckner, G and Kuwayama, H and Schaap, P and Urushihara, H and Baldauf, SL}, title = {Root of Dictyostelia based on 213 universal proteins.}, journal = {Molecular phylogenetics and evolution}, volume = {92}, number = {}, pages = {53-62}, doi = {10.1016/j.ympev.2015.05.017}, pmid = {26048704}, issn = {1095-9513}, support = {BB/E016308//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Amoeba/chemistry/metabolism ; Bayes Theorem ; Dictyostelium/*classification/genetics/*metabolism ; Genome/genetics ; *Phylogeny ; Proteins/*analysis/chemistry ; RNA, Ribosomal/genetics ; }, abstract = {Dictyostelia are common soil microbes that can aggregate when starved to form multicellular fruiting bodies, a characteristic that has also led to their long history of study and widespread use as model systems. Ribosomal RNA phylogeny of Dictyostelia identified four major divisions (Groups 1-4), none of which correspond to traditional genera. Group 1 was also tentatively identified as sister lineage to the other three Groups, although not consistently or with strong support. We tested the dictyostelid root using universal protein-coding genes identified by exhaustive comparison of six completely sequenced dictyostelid genomes, which include representatives of all four major molecular Groups. A set of 213 genes are low-copy number in all genomes, present in at least one amoebozoan outgroup taxon (Acanthamoeba castellanii or Physarum polycephalum), and phylogenetically congruent. Phylogenetic analysis of a concatenation of the deduced protein sequences produces a single topology dividing Dictyostelia into two major divisions: Groups 1+2 and Groups 3+4. All clades in the tree are fully supported by maximum likelihood and Bayesian inference, and all alternative roots are unambiguously rejected by the approximately unbiased (AU) test. The 1+2, 3+4 root is also fully supported even after deleting clusters with strong individual support for this root, or concatenating all clusters with low support for alternative roots. The 213 putatively ancestral amoebozoan proteins encode a wide variety of functions including 21 KOG categories out of a total of 25. These comprehensive analyses and consistent results indicate that it is time for full taxonomic revision of Dictyostelia, which will also enable more effective exploitation of its unique potential as an evolutionary model system.}, } @article {pmid26047467, year = {2015}, author = {Wideman, JG and Moore, BP}, title = {The Evolutionary History of MAPL (Mitochondria-Associated Protein Ligase) and Other Eukaryotic BAM/GIDE Domain Proteins.}, journal = {PloS one}, volume = {10}, number = {6}, pages = {e0128795}, pmid = {26047467}, issn = {1932-6203}, mesh = {Animals ; Biological Evolution ; Fungal Proteins/chemistry/genetics ; Fungi/chemistry/genetics ; Humans ; *Phylogeny ; Plant Proteins/chemistry/genetics ; Plants/chemistry/genetics ; Protein Structure, Tertiary ; Ubiquitin-Protein Ligases/chemistry/*genetics ; }, abstract = {MAPL (mitochondria-associated protein ligase, also called MULAN/GIDE/MUL1) is a multifunctional mitochondrial outer membrane protein found in human cells that contains a unique BAM (beside a membrane) domain and a C-terminal RING-finger domain. MAPL has been implicated in several processes that occur in animal cells such as NF-kB activation, innate immunity and antiviral signaling, suppression of PINK1/parkin defects, mitophagy in skeletal muscle, and caspase-dependent apoptosis. Previous studies demonstrated that the BAM domain is present in diverse organisms in which most of these processes do not occur, including plants, archaea, and bacteria. Thus the conserved function of MAPL and its BAM domain remains an open question. In order to gain insight into its conserved function, we investigated the evolutionary origins of MAPL by searching for homologues in predicted proteomes of diverse eukaryotes. We show that MAPL proteins with a conserved BAM-RING architecture are present in most animals, protists closely related to animals, a single species of fungus, and several multicellular plants and related green algae. Phylogenetic analysis demonstrated that eukaryotic MAPL proteins originate from a common ancestor and not from independent horizontal gene transfers from bacteria. We also determined that two independent duplications of MAPL occurred, one at the base of multicellular plants and another at the base of vertebrates. Although no other eukaryote genome examined contained a verifiable MAPL orthologue, BAM domain-containing proteins were identified in the protists Bigelowiella natans and Ectocarpus siliculosis. Phylogenetic analyses demonstrated that these proteins are more closely related to prokaryotic BAM proteins and therefore likely arose from independent horizontal gene transfers from bacteria. We conclude that MAPL proteins with BAM-RING architectures have been present in the holozoan and viridiplantae lineages since their very beginnings. Our work paves the way for future studies into MAPL function in alternative model organisms like Capsaspora owczarzaki and Chlamydomonas reinhardtii that will help to answer the question of MAPL's ancestral function in ways that cannot be answered by studying animal cells alone.}, } @article {pmid26041885, year = {2015}, author = {Kurakin, A and Bredesen, DE}, title = {Dynamic self-guiding analysis of Alzheimer's disease.}, journal = {Oncotarget}, volume = {6}, number = {16}, pages = {14092-14122}, pmid = {26041885}, issn = {1949-2553}, support = {R21 AG036975/AG/NIA NIH HHS/United States ; AG16570/AG/NIA NIH HHS/United States ; AG034427/AG/NIA NIH HHS/United States ; AG036975/AG/NIA NIH HHS/United States ; P50 AG016570/AG/NIA NIH HHS/United States ; R01 AG034427/AG/NIA NIH HHS/United States ; }, mesh = {Algorithms ; Alzheimer Disease/*metabolism/*pathology ; Amyloid beta-Protein Precursor/metabolism ; Cell Adhesion/physiology ; Humans ; }, abstract = {We applied a self-guiding evolutionary algorithm to initiate the synthesis of the Alzheimer's disease-related data and literature. A protein interaction network associated with amyloid-beta precursor protein (APP) and a seed model that treats Alzheimer's disease as progressive dysregulation of APP-associated signaling were used as dynamic "guides" and structural "filters" in the recursive search, analysis, and assimilation of data to drive the evolution of the seed model in size, detail, and complexity. Analysis of data and literature across sub-disciplines and system-scale discovery platforms suggests a key role of dynamic cytoskeletal connectivity in the stability, plasticity, and performance of multicellular networks and architectures. Chronic impairment and/or dysregulation of cell adhesions/synapses, cytoskeletal networks, and/or reversible epithelial-to-mesenchymal-like transitions, which enable and mediate the stable and coherent yet dynamic and reconfigurable multicellular architectures, may lead to the emergence and persistence of the disordered, wound-like pockets/microenvironments of chronically disconnected cells. Such wound-like microenvironments support and are supported by pro-inflammatory, pro-secretion, de-differentiated cellular phenotypes with altered metabolism and signaling. The co-evolution of wound-like microenvironments and their inhabitants may lead to the selection and stabilization of degenerated cellular phenotypes, via acquisition of epigenetic modifications and mutations, which eventually result in degenerative disorders such as cancer and Alzheimer's disease.}, } @article {pmid26040593, year = {2015}, author = {Vural, DC and Isakov, A and Mahadevan, L}, title = {The organization and control of an evolving interdependent population.}, journal = {Journal of the Royal Society, Interface}, volume = {12}, number = {108}, pages = {20150044}, pmid = {26040593}, issn = {1742-5662}, mesh = {*Biological Evolution ; *Game Theory ; *Models, Biological ; *Selection, Genetic ; }, abstract = {Starting with Darwin, biologists have asked how populations evolve from a low fitness state that is evolutionarily stable to a high fitness state that is not. Specifically of interest is the emergence of cooperation and multicellularity where the fitness of individuals often appears in conflict with that of the population. Theories of social evolution and evolutionary game theory have produced a number of fruitful results employing two-state two-body frameworks. In this study, we depart from this tradition and instead consider a multi-player, multi-state evolutionary game, in which the fitness of an agent is determined by its relationship to an arbitrary number of other agents. We show that populations organize themselves in one of four distinct phases of interdependence depending on one parameter, selection strength. Some of these phases involve the formation of specialized large-scale structures. We then describe how the evolution of independence can be manipulated through various external perturbations.}, } @article {pmid26040592, year = {2015}, author = {Brumley, DR and Polin, M and Pedley, TJ and Goldstein, RE}, title = {Metachronal waves in the flagellar beating of Volvox and their hydrodynamic origin.}, journal = {Journal of the Royal Society, Interface}, volume = {12}, number = {108}, pages = {20141358}, pmid = {26040592}, issn = {1742-5662}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Flagella/*physiology ; Hydrodynamics ; *Models, Biological ; Volvox/*physiology ; }, abstract = {Groups of eukaryotic cilia and flagella are capable of coordinating their beating over large scales, routinely exhibiting collective dynamics in the form of metachronal waves. The origin of this behavior--possibly influenced by both mechanical interactions and direct biological regulation--is poorly understood, in large part due to a lack of quantitative experimental studies. Here we characterize in detail flagellar coordination on the surface of the multicellular alga Volvox carteri, an emerging model organism for flagellar dynamics. Our studies reveal for the first time that the average metachronal coordination observed is punctuated by periodic phase defects during which synchrony is partial and limited to specific groups of cells. A minimal model of hydrodynamically coupled oscillators can reproduce semi-quantitatively the characteristics of the average metachronal dynamics, and the emergence of defects. We systematically study the model's behaviour by assessing the effect of changing intrinsic rotor characteristics, including oscillator stiffness and the nature of their internal driving force, as well as their geometric properties and spatial arrangement. Our results suggest that metachronal coordination follows from deformations in the oscillators' limit cycles induced by hydrodynamic stresses, and that defects result from sufficiently steep local biases in the oscillators' intrinsic frequencies. Additionally, we find that random variations in the intrinsic rotor frequencies increase the robustness of the average properties of the emergent metachronal waves.}, } @article {pmid26031902, year = {2015}, author = {Baroux, C and Autran, D}, title = {Chromatin dynamics during cellular differentiation in the female reproductive lineage of flowering plants.}, journal = {The Plant journal : for cell and molecular biology}, volume = {83}, number = {1}, pages = {160-176}, pmid = {26031902}, issn = {1365-313X}, mesh = {Cell Differentiation ; Chromatin/genetics/*metabolism/ultrastructure ; DNA Methylation ; Epigenesis, Genetic ; Gene Expression Regulation, Plant ; Meiosis ; Ovule/*physiology ; Plant Cells/*physiology ; }, abstract = {Sexual reproduction in flowering plants offers a number of remarkable aspects to developmental biologists. First, the spore mother cells - precursors of the plant reproductive lineage - are specified late in development, as opposed to precocious germline isolation during embryogenesis in most animals. Second, unlike in most animals where meiosis directly produces gametes, plant meiosis entails the differentiation of a multicellular, haploid gametophyte, within which gametic as well as non-gametic accessory cells are formed. These observations raise the question of the factors inducing and modus operandi of cell fate transitions that originate in floral tissues and gametophytes, respectively. Cell fate transitions in the reproductive lineage imply cellular reprogramming operating at the physiological, cytological and transcriptome level, but also at the chromatin level. A number of observations point to large-scale chromatin reorganization events associated with cellular differentiation of the female spore mother cells and of the female gametes. These include a reorganization of the heterochromatin compartment, the genome-wide alteration of the histone modification landscape, and the remodeling of nucleosome composition. The dynamic expression of DNA methyltransferases and actors of small RNA pathways also suggest additional, global epigenetic alterations that remain to be characterized. Are these events a cause or a consequence of cellular differentiation, and how do they contribute to cell fate transition? Does chromatin dynamics induce competence for immediate cellular functions (meiosis, fertilization), or does it also contribute long-term effects in cellular identity and developmental competence of the reproductive lineage? This review attempts to review these fascinating questions.}, } @article {pmid26021328, year = {2015}, author = {Santos, J and Monteagudo, Á}, title = {Analysis of behaviour transitions in tumour growth using a cellular automaton simulation.}, journal = {IET systems biology}, volume = {9}, number = {3}, pages = {75-87}, pmid = {26021328}, issn = {1751-8849}, mesh = {Animals ; Carcinogenesis/*pathology ; Cell Proliferation ; Computer Simulation ; Humans ; *Models, Biological ; Neoplasms/*pathology/*physiopathology ; Spheroids, Cellular/*pathology/*physiology ; }, abstract = {The authors used computational biology as an approach for analysing the emergent dynamics of tumour growth at cellular level. They applied cellular automata for modelling the behaviour of cells when the main cancer cell hallmarks are present. Their model is oriented to mimic the development of multicellular spheroids of tumour cells. In their modelling, cells have a genome associated with the different cancer hallmarks, indicating if those are acquired as a consequence of mutations. The presence of the cancer hallmarks defines cell states and cell mitotic behaviours. These hallmarks are associated with a series of parameters, and depending on their values and the activation of the hallmarks in each of the cells, the system can evolve to different dynamics. With the simulation tool the authors performed an analysis of the first phases of cancer growth, using different and alternative strategies: firstly, studying the evolution of cancer cells and hallmarks in different representative situations regarding initial conditions and parameters, analysing the relative importance of the hallmarks for tumour progression; secondly, being the focus of this work, inspecting the behaviour transitions when the cancer cells are killed with a given probability during the cellular system progression.}, } @article {pmid26018043, year = {2015}, author = {Ho, HI and Shaulsky, G}, title = {Temporal regulation of kin recognition maintains recognition-cue diversity and suppresses cheating.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {7144}, pmid = {26018043}, issn = {2041-1723}, support = {CA125123/CA/NCI NIH HHS/United States ; HD007495/HD/NICHD NIH HHS/United States ; T32 HD007495/HD/NICHD NIH HHS/United States ; U54 HD007495/HD/NICHD NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; DK56338/DK/NIDDK NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; R01 GM098276/GM/NIGMS NIH HHS/United States ; P30 HD007495/HD/NICHD NIH HHS/United States ; }, mesh = {Biological Evolution ; Cues ; Dictyostelium/*genetics/metabolism ; Fruiting Bodies, Fungal/*genetics/metabolism ; *Genetic Variation ; Membrane Proteins/*genetics/metabolism ; *Microbial Interactions ; Polymorphism, Genetic ; Protozoan Proteins/*genetics/metabolism ; Spores, Protozoan ; }, abstract = {Kin recognition, the ability to distinguish kin from non-kin, can facilitate cooperation between relatives. Evolutionary theory predicts that polymorphism in recognition cues, which is essential for effective recognition, would be unstable. Individuals carrying rare recognition cues would benefit less from social interactions than individuals with common cues, leading to loss of the genetic-cue diversity. We test this evolutionary hypothesis in Dictyostelium discoideum, which forms multicellular fruiting bodies by aggregation and utilizes two polymorphic membrane proteins to facilitate preferential cooperation. Surprisingly, we find that rare recognition variants are tolerated and maintain their frequencies among incompatible majority during development. Although the rare variants are initially excluded from the aggregates, they subsequently rejoin the aggregate and produce spores. Social cheating is also refrained in late development, thus limiting the cost of chimerism. Our results suggest a potential mechanism to sustain the evolutionary stability of kin-recognition genes and to suppress cheating.}, } @article {pmid26014922, year = {2015}, author = {Torday, JS}, title = {The cell as the mechanistic basis for evolution.}, journal = {Wiley interdisciplinary reviews. Systems biology and medicine}, volume = {7}, number = {5}, pages = {275-284}, doi = {10.1002/wsbm.1305}, pmid = {26014922}, issn = {1939-005X}, mesh = {Animals ; *Biological Evolution ; Genotype ; Humans ; Lung/cytology/metabolism ; Phenotype ; *Phylogeny ; }, abstract = {The First Principles for Physiology originated in and emanate from the unicellular state of life. Viewing physiology as a continuum from unicellular to multicellular organisms provides fundamental insight to ontogeny and phylogeny as a functionally integral whole. Such mechanisms are most evident under conditions of physiologic stress; all of the molecular pathways that evolved in service to the vertebrate water-land transition aided and abetted the evolution of the vertebrate lung, for example. Reduction of evolution to cell biology has an important scientific feature—it is predictive. One implication of this perspective on evolution is the likelihood that it is the unicellular state that is actually the object of selection. By looking at the process of evolution from its unicellular origins, the causal relationships between genotype and phenotype are revealed, as are many other aspects of physiology and medicine that have remained anecdotal and counter-intuitive. Evolutionary development can best be considered as a cyclical, epigenetic, reiterative environmental assessment process, originating from the unicellular state, both forward and backward, to sustain and perpetuate unicellular homeostasis.}, } @article {pmid26005236, year = {2015}, author = {Keijzer, F}, title = {Moving and sensing without input and output: early nervous systems and the origins of the animal sensorimotor organization.}, journal = {Biology & philosophy}, volume = {30}, number = {3}, pages = {311-331}, pmid = {26005236}, issn = {0169-3867}, abstract = {It remains a standing problem how and why the first nervous systems evolved. Molecular and genomic information is now rapidly accumulating but the macroscopic organization and functioning of early nervous systems remains unclear. To explore potential evolutionary options, a coordination centered view is discussed that diverges from a standard input-output view on early nervous systems. The scenario involved, the skin brain thesis (SBT), stresses the need to coordinate muscle-based motility at a very early stage. This paper addresses how this scenario with its focus on coordination also deals with sensory aspects. It will be argued that the neural structure required to coordinate extensive sheets of contractile tissue for motility provides the starting point for a new multicellular organized form of sensing. Moving a body by muscle contraction provides the basis for a multicellular organization that is sensitive to external surface structure at the scale of the animal body. Instead of thinking about early nervous systems as being connected to the environment merely through input and output, the implication developed here is that early nervous systems provide the foundation for a highly specific animal sensorimotor organization in which neural activity directly reflects bodily and environmental spatiotemporal structure. While the SBT diverges from the input-output view, it is closely linked to and supported by ongoing work on embodied approaches to intelligence to which it adds a new interpretation of animal embodiment and sensorimotor organization.}, } @article {pmid25994183, year = {2015}, author = {Labeeuw, L and Martone, PT and Boucher, Y and Case, RJ}, title = {Ancient origin of the biosynthesis of lignin precursors.}, journal = {Biology direct}, volume = {10}, number = {}, pages = {23}, pmid = {25994183}, issn = {1745-6150}, mesh = {Alcohols/chemistry ; Aldehyde Oxidoreductases/metabolism ; Arabidopsis/genetics ; Biological Evolution ; Chlamydomonas/*genetics ; Chlorella/*genetics ; Computational Biology ; Dinoflagellida/genetics ; Evolution, Molecular ; Gene Transfer, Horizontal ; Haptophyta/genetics ; Lignin/*biosynthesis ; Likelihood Functions ; Photosynthesis ; Phylogeny ; Selaginellaceae/genetics ; }, abstract = {BACKGROUND: Lignin plays an important role in plant structural support and water transport, and is considered one of the hallmarks of land plants. The recent discovery of lignin or its precursors in various algae has raised questions on the evolution of its biosynthetic pathway, which could be much more ancient than previously thought. To determine the taxonomic distribution of the lignin biosynthesis genes, we screened all publicly available genomes of algae and their closest non-photosynthetic relatives, as well as representative land plants. We also performed phylogenetic analysis of these genes to decipher the evolution and origin(s) of lignin biosynthesis.

RESULTS: Enzymes involved in making p-coumaryl alcohol, the simplest lignin monomer, are found in a variety of photosynthetic eukaryotes, including diatoms, dinoflagellates, haptophytes, cryptophytes as well as green and red algae. Phylogenetic analysis of these enzymes suggests that they are ancient and spread to some secondarily photosynthetic lineages when they acquired red and/or green algal endosymbionts. In some cases, one or more of these enzymes was likely acquired through lateral gene transfer (LGT) from bacteria.

CONCLUSIONS: Genes associated with p-coumaryl alcohol biosynthesis are likely to have evolved long before the transition of photosynthetic eukaryotes to land. The original function of this lignin precursor is therefore unlikely to have been related to water transport. We suggest that it participates in the biological defense of some unicellular and multicellular algae.}, } @article {pmid25993239, year = {2015}, author = {Shlush, LI and Hershkovitz, D}, title = {Clonal evolution models of tumor heterogeneity.}, journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting}, volume = {}, number = {}, pages = {e662-5}, doi = {10.14694/EdBook_AM.2015.35.e662}, pmid = {25993239}, issn = {1548-8756}, mesh = {*Clonal Evolution ; Genetic Heterogeneity ; Humans ; Neoplasms/diagnosis/genetics/*pathology ; Neoplastic Stem Cells/*pathology ; Precancerous Conditions/diagnosis/genetics/pathology ; }, abstract = {Somatic/clonal evolution is the process of sequential acquisition of vertically transmittable genetic/epigenetic elements in multicellular organisms. Cancer is the result of somatic evolution. Understanding the processes that shape the evolution of individual tumors might help us to treat cancer more efficiently. The initiating genetic/epigenetic events occur in functional cells and provide the cell of origin a selective advantage under a changing environment. The initiating genetic events tend to be enriched in specific tissues (and are sometimes specific for those tissues), as different tissues undergo different changes in the environment that will activate selective forces on different cells of origin. For the initial clonal expansion to occur premalignant clones need to have a relative fitness advantage over their competitors. It is estimated that the premalignant phase can take several years. Once the premalignant clonal expansion is established, the premalignant cells will contribute to the changing environment and will start competing among themselves. In late stages of cancer evolution the environmental changes might be similar across different tissues, including a lack of physical space, a shortage of energy, and activation of the immune system, and more and more of the hallmarks of cancer will evolve. In this review we will explore the possible clinical relevance of the heterogeneity that evolves during this long somatic evolution. Above all, it should be stressed that the earlier the clonal expansion is recognized, the less diverse and less fit for survival the cells in the population are.}, } @article {pmid25991256, year = {2015}, author = {Robu, A and Stoicu-Tivadar, L and Robu, N and Neagu, A}, title = {Computational study of the self-assembly of two different cell populations in contact with a biomaterial.}, journal = {Studies in health technology and informatics}, volume = {210}, number = {}, pages = {761-765}, pmid = {25991256}, issn = {1879-8365}, mesh = {Biocompatible Materials/*chemistry ; Cell Adhesion/*physiology ; Cell Aggregation/*physiology ; Cell Movement/*physiology ; Computer Simulation ; *Models, Biological ; Tissue Engineering/*methods ; }, abstract = {The organisation of a heterotypic multicellular system is intensely studied in developmental biology, tissue engineering and regenerative medicine.To address this problem, we have created a computational model of a biological system made of two cell populations of various cohesivities, and simulated its evolution on the surface of biomaterials of different adhesivities. To this end, it was necessary to extend our SIMMMC application with algorithms that treat two cell types. We have observed, in accordance with experiments that, depending on the strength of cell-substrate adhesion, different structures emerge by the self-assembly of the two cell populations. The agreement with experimental results validates the extended version of the SIMMMC application, suggesting that this tool might offer useful insights for tissue engineers.}, } @article {pmid25984697, year = {2015}, author = {Sarioglu, AF and Aceto, N and Kojic, N and Donaldson, MC and Zeinali, M and Hamza, B and Engstrom, A and Zhu, H and Sundaresan, TK and Miyamoto, DT and Luo, X and Bardia, A and Wittner, BS and Ramaswamy, S and Shioda, T and Ting, DT and Stott, SL and Kapur, R and Maheswaran, S and Haber, DA and Toner, M}, title = {A microfluidic device for label-free, physical capture of circulating tumor cell clusters.}, journal = {Nature methods}, volume = {12}, number = {7}, pages = {685-691}, pmid = {25984697}, issn = {1548-7105}, support = {U01 EB012493/EB/NIBIB NIH HHS/United States ; R01 EB008047/EB/NIBIB NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; K12 CA087723/CA/NCI NIH HHS/United States ; P41 EB002503/EB/NIBIB NIH HHS/United States ; }, mesh = {Breast Neoplasms/pathology ; Cell Line, Tumor ; Female ; Humans ; Immunohistochemistry ; Male ; *Microfluidic Analytical Techniques ; *Neoplastic Cells, Circulating ; Prostatic Neoplasms/pathology ; Sequence Analysis, RNA ; }, abstract = {Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC clusters). Existing technologies for CTC enrichment are designed to isolate single CTCs, and although CTC clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here we developed a microchip technology (the Cluster-Chip) to capture CTC clusters independently of tumor-specific markers from unprocessed blood. CTC clusters are isolated through specialized bifurcating traps under low-shear stress conditions that preserve their integrity, and even two-cell clusters are captured efficiently. Using the Cluster-Chip, we identified CTC clusters in 30-40% of patients with metastatic breast or prostate cancer or with melanoma. RNA sequencing of CTC clusters confirmed their tumor origin and identified tissue-derived macrophages within the clusters. Efficient capture of CTC clusters will enable the detailed characterization of their biological properties and role in metastasis.}, } @article {pmid25983206, year = {2015}, author = {Kawashima, T and Lorković, ZJ and Nishihama, R and Ishizaki, K and Axelsson, E and Yelagandula, R and Kohchi, T and Berger, F}, title = {Diversification of histone H2A variants during plant evolution.}, journal = {Trends in plant science}, volume = {20}, number = {7}, pages = {419-425}, doi = {10.1016/j.tplants.2015.04.005}, pmid = {25983206}, issn = {1878-4372}, mesh = {Amino Acid Sequence ; *Biological Evolution ; Histones/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Plants/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {Among eukaryotes, the four core histones show an extremely high conservation of their structure and form nucleosomes that compact, protect, and regulate access to genetic information. Nevertheless, in multicellular eukaryotes the two families, histone H2A and histone H3, have diversified significantly in key residues. We present a phylogenetic analysis across the green plant lineage that reveals an early diversification of the H2A family in unicellular green algae and remarkable expansions of H2A variants in flowering plants. We define motifs and domains that differentiate plant H2A proteins into distinct variant classes. In non-flowering land plants, we identify a new class of H2A variants and propose their possible role in the emergence of the H2A.W variant class in flowering plants.}, } @article {pmid25976758, year = {2015}, author = {Otten, AB and Smeets, HJ}, title = {Evolutionary defined role of the mitochondrial DNA in fertility, disease and ageing.}, journal = {Human reproduction update}, volume = {21}, number = {5}, pages = {671-689}, doi = {10.1093/humupd/dmv024}, pmid = {25976758}, issn = {1460-2369}, mesh = {Aging/*genetics ; Animals ; *Biological Evolution ; DNA, Mitochondrial/*genetics/*physiology ; Fertility/*genetics ; Fungi/genetics ; Genome/genetics ; Humans ; Mutation/genetics ; Phylogeny ; Plants/genetics ; Reproduction/genetics ; }, abstract = {BACKGROUND: The endosymbiosis of an alpha-proteobacterium and a eubacterium a billion years ago paved the way for multicellularity and enabled eukaryotes to flourish. The selective advantage for the host was the acquired ability to generate large amounts of intracellular hydrogen-dependent adenosine triphosphate. The price was increased reactive oxygen species (ROS) inside the eukaryotic cell, causing high mutation rates of the mitochondrial DNA (mtDNA). According to the Muller's ratchet theory, this accumulation of mutations in asexually transmitted mtDNA would ultimately lead to reduced reproductive fitness and eventually extinction. However, mitochondria have persisted over the course of evolution, initially due to a rapid, extreme evolutionary reduction of the mtDNA content. After the phylogenetic divergence of eukaryotes into animals, fungi and plants, differences in evolution of the mtDNA occurred with different adaptations for coping with the mutation burden within these clades. As a result, mitochondrial evolutionary mechanisms have had a profound effect on human adaptation, fertility, healthy reproduction, mtDNA disease manifestation and transmission and ageing. An understanding of these mechanisms might elucidate novel approaches for treatment and prevention of mtDNA disease.

METHODS: The scientific literature was investigated to determine how mtDNA evolved in animals, plants and fungi. Furthermore, the different mechanisms of mtDNA inheritance and of balancing Muller's ratchet in these species were summarized together with the consequences of these mechanisms for human health and reproduction.

RESULTS: Animal, plant and fungal mtDNA have evolved differently. Animals have compact genomes, little recombination, a stable number of genes and a high mtDNA copy number, whereas plants have larger genomes with variable gene counts, a low mtDNA copy number and many recombination events. Fungal mtDNA is somewhere in between. In plants, the mtDNA mutation rate is kept low by effective ROS defence and efficient recombination-mediated mtDNA repair. In animal mtDNA, these mechanisms are not or less well-developed and the detrimental mutagenesis events are controlled by a high mtDNA copy number in combination with a genetic bottleneck and purifying selection during transmission. The mtDNA mutation rates in animals are higher than in plants, which allow mobile animals to adapt more rapidly to various environmental conditions in terms of energy production, whereas static plants do not have this need. Although at the level of the species, these mechanisms have been extremely successful, they can have adverse effects for the individual, resulting, in humans, in severe or unpredictably segregating mtDNA diseases, as well as fertility problems and unhealthy ageing.

CONCLUSIONS: Understanding the forces and processes that underlie mtDNA evolution among different species increases our knowledge on the detrimental consequences that individuals can have from these evolutionary end-points. Alternative outcomes in animals, fungi and plants will lead to a better understanding of the inheritance of mtDNA disorders and mtDNA-related fertility problems. These will allow the development of options to ameliorate, cure and/or prevent mtDNA diseases and mtDNA-related fertility problems.}, } @article {pmid25976756, year = {2015}, author = {Breugelmans, B and Ansell, BR and Young, ND and Amani, P and Stroehlein, AJ and Sternberg, PW and Jex, AR and Boag, PR and Hofmann, A and Gasser, RB}, title = {Flatworms have lost the right open reading frame kinase 3 gene during evolution.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {9417}, pmid = {25976756}, issn = {2045-2322}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Biological Evolution ; Evolution, Molecular ; Open Reading Frames/*genetics ; Platyhelminths/*genetics ; Protein Serine-Threonine Kinases/*genetics ; }, abstract = {All multicellular organisms studied to date have three right open reading frame kinase genes (designated riok-1, riok-2 and riok-3). Current evidence indicates that riok-1 and riok-2 have essential roles in ribosome biosynthesis, and that the riok-3 gene assists this process. In the present study, we conducted a detailed bioinformatic analysis of the riok gene family in 25 parasitic flatworms (platyhelminths) for which extensive genomic and transcriptomic data sets are available. We found that none of the flatworms studied have a riok-3 gene, which is unprecedented for multicellular organisms. We propose that, unlike in other eukaryotes, the loss of RIOK-3 from flatworms does not result in an evolutionary disadvantage due to the unique biology and physiology of this phylum. We show that the loss of RIOK-3 coincides with a loss of particular proteins associated with essential cellular pathways linked to cell growth and apoptosis. These findings indicate multiple, key regulatory functions of RIOK-3 in other metazoan species. Taking advantage of a known partial crystal structure of human RIOK-1, molecular modelling revealed variability in nucleotide binding sites between flatworm and human RIOK proteins.}, } @article {pmid25964737, year = {2015}, author = {Woelfle, R and D'Aquila, AL and Pavlović, T and Husić, M and Lovejoy, DA}, title = {Ancient interaction between the teneurin C-terminal associated peptides (TCAP) and latrophilin ligand-receptor coupling: a role in behavior.}, journal = {Frontiers in neuroscience}, volume = {9}, number = {}, pages = {146}, pmid = {25964737}, issn = {1662-4548}, abstract = {Teneurins are multifunctional transmembrane proteins that are found in all multicellular animals and exist as four paralogous forms in vertebrates. They are highly expressed in the central nervous system, where they exert their effects, in part, by high-affinity binding to latrophilin (LPHN), a G-protein coupled receptor (GPCR) related to the adhesion and secretin GPCR families. The teneurin C-terminal associated peptides (TCAPs) are encoded by the terminal exon of all four teneurins, where TCAPs 1 and 3 are independently transcribed as soluble peptides, and TCAPs 2 and 4 remain tethered to their teneurin proprotein. Synthetic TCAP-1 interacts with LPHN, with an association with β-dystroglycan, to induce a tissue-dependent signal cascade to modulate cytoskeletal dynamics. TCAP-1 reduces stress-induced behaviors associated with anxiety, addiction and depression in a variety of models, in part, by regulating synaptic plasticity. Therefore, the TCAP-1-teneurin-LPHN interaction represents a novel receptor-ligand model and may represent a key mechanism underlying the association of behavior and neurological conditions.}, } @article {pmid25964342, year = {2015}, author = {West, SA and Fisher, RM and Gardner, A and Kiers, ET}, title = {Major evolutionary transitions in individuality.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {33}, pages = {10112-10119}, pmid = {25964342}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; Communication ; Cooperative Behavior ; Diploidy ; Ecology ; Female ; Genetic Drift ; Haploidy ; Humans ; Individuality ; Male ; Social Behavior ; Symbiosis/*physiology ; }, abstract = {The evolution of life on earth has been driven by a small number of major evolutionary transitions. These transitions have been characterized by individuals that could previously replicate independently, cooperating to form a new, more complex life form. For example, archaea and eubacteria formed eukaryotic cells, and cells formed multicellular organisms. However, not all cooperative groups are en route to major transitions. How can we explain why major evolutionary transitions have or haven't taken place on different branches of the tree of life? We break down major transitions into two steps: the formation of a cooperative group and the transformation of that group into an integrated entity. We show how these steps require cooperation, division of labor, communication, mutual dependence, and negligible within-group conflict. We find that certain ecological conditions and the ways in which groups form have played recurrent roles in driving multiple transitions. In contrast, we find that other factors have played relatively minor roles at many key points, such as within-group kin discrimination and mechanisms to actively repress competition. More generally, by identifying the small number of factors that have driven major transitions, we provide a simpler and more unified description of how life on earth has evolved.}, } @article {pmid25963254, year = {2015}, author = {Mishra, H and Saran, S}, title = {Classification and expression analyses of homeobox genes from Dictyostelium discoideum.}, journal = {Journal of biosciences}, volume = {40}, number = {2}, pages = {241-255}, pmid = {25963254}, issn = {0973-7138}, mesh = {Amino Acid Sequence ; Animals ; Dictyostelium/*genetics ; Genes, Homeobox/*genetics ; Genome/genetics ; Homeodomain Proteins/*classification/*genetics ; Molecular Sequence Data ; Phylogeny ; Promoter Regions, Genetic/*genetics ; Sequence Alignment ; }, abstract = {Homeobox genes are compared between genomes in an attempt to understand the evolution of animal development. The ability of the protist, Dictyostelium discoideum, to shift between uni- and multicellularity makes this group ideal for studying the genetic changes that may have occurred during this transition. We present here the first genome-wide classification and comparative genomic analysis of the 14 homeobox genes present in D. discoideum. Based on the structural alignment of the homeodomains, they can be broadly divided into TALE and non-TALE classes. When individual homeobox genes were compared with members of known class or family, we could further classify them into 3 groups, namely, TALE, OTHER and NOVEL classes, but no HOX family was found. The 5 members of TALE class could be further divided into PBX, PKNOX, IRX and CUP families; 4 homeobox genes classified as NOVEL did not show any similarity to any known homeobox genes; while the remaining 5 were classified as OTHERS as they did show certain degree of similarity to few known homeobox genes. No unique RNA expression pattern during development of D. discoideum emerged for members of an individual group. Putative promoter analysis revealed binding sites for few homeobox transcription factors among many probable factors.}, } @article {pmid25960408, year = {2015}, author = {Kraushaar, T and Brückner, S and Veelders, M and Rhinow, D and Schreiner, F and Birke, R and Pagenstecher, A and Mösch, HU and Essen, LO}, title = {Interactions by the Fungal Flo11 Adhesin Depend on a Fibronectin Type III-like Adhesin Domain Girdled by Aromatic Bands.}, journal = {Structure (London, England : 1993)}, volume = {23}, number = {6}, pages = {1005-1017}, doi = {10.1016/j.str.2015.03.021}, pmid = {25960408}, issn = {1878-4186}, mesh = {Amino Acid Sequence ; Amino Acids, Aromatic/chemistry ; Cell Adhesion/*physiology ; Fibronectins/*metabolism ; Membrane Glycoproteins/*chemistry/genetics/*metabolism ; *Models, Molecular ; Molecular Sequence Data ; Multigene Family/*genetics ; Phylogeny ; Protein Structure, Tertiary ; Saccharomyces cerevisiae/*chemistry ; Saccharomyces cerevisiae Proteins/*chemistry/genetics/*metabolism ; }, abstract = {Saccharomyces cerevisiae harbors a family of GPI-anchored cell wall proteins for interaction with its environment. The flocculin Flo11, a major representative of these fungal adhesins, confers formation of different types of multicellular structures such as biofilms, flors, or filaments. To understand these environment-dependent growth phenotypes on a molecular level, we solved the crystal structure of the N-terminal Flo11A domain at 0.89-Å resolution. Besides a hydrophobic apical region, the Flo11A domain consists of a β sandwich of the fibronectin type III domain (FN3). We further show that homophilic Flo11-Flo11 interactions and heterophilic Flo11-plastic interactions solely depend on the Flo11A domain and are strongly pH dependent. These functions of Flo11A involve an apical region with its surface-exposed aromatic band, which is accompanied by acidic stretches. Together with electron microscopic reconstructions of yeast cell-cell contact sites, our data suggest that Flo11 acts as a spacer-like, pH-sensitive adhesin that resembles a membrane-tethered hydrophobin.}, } @article {pmid25954305, year = {2015}, author = {Davila-Velderrain, J and Martinez-Garcia, JC and Alvarez-Buylla, ER}, title = {Modeling the epigenetic attractors landscape: toward a post-genomic mechanistic understanding of development.}, journal = {Frontiers in genetics}, volume = {6}, number = {}, pages = {160}, pmid = {25954305}, issn = {1664-8021}, abstract = {Robust temporal and spatial patterns of cell types emerge in the course of normal development in multicellular organisms. The onset of degenerative diseases may result from altered cell fate decisions that give rise to pathological phenotypes. Complex networks of genetic and non-genetic components underlie such normal and altered morphogenetic patterns. Here we focus on the networks of regulatory interactions involved in cell-fate decisions. Such networks modeled as dynamical non-linear systems attain particular stable configurations on gene activity that have been interpreted as cell-fate states. The network structure also restricts the most probable transition patterns among such states. The so-called Epigenetic Landscape (EL), originally proposed by C. H. Waddington, was an early attempt to conceptually explain the emergence of developmental choices as the result of intrinsic constraints (regulatory interactions) shaped during evolution. Thanks to the wealth of molecular genetic and genomic studies, we are now able to postulate gene regulatory networks (GRN) grounded on experimental data, and to derive EL models for specific cases. This, in turn, has motivated several mathematical and computational modeling approaches inspired by the EL concept, that may be useful tools to understand and predict cell-fate decisions and emerging patterns. In order to distinguish between the classical metaphorical EL proposal of Waddington, we refer to the Epigenetic Attractors Landscape (EAL), a proposal that is formally framed in the context of GRNs and dynamical systems theory. In this review we discuss recent EAL modeling strategies, their conceptual basis and their application in studying the emergence of both normal and pathological developmental processes. In addition, we discuss how model predictions can shed light into rational strategies for cell fate regulation, and we point to challenges ahead.}, } @article {pmid25944666, year = {2015}, author = {Dall, SR and McNamara, JM and Leimar, O}, title = {Genes as cues: phenotypic integration of genetic and epigenetic information from a Darwinian perspective.}, journal = {Trends in ecology & evolution}, volume = {30}, number = {6}, pages = {327-333}, doi = {10.1016/j.tree.2015.04.002}, pmid = {25944666}, issn = {1872-8383}, mesh = {Animals ; Bayes Theorem ; *Biological Evolution ; *Epigenesis, Genetic ; Gene-Environment Interaction ; *Genes ; Growth and Development/genetics ; Phenotype ; Plant Development/genetics ; Selection, Genetic ; }, abstract = {The development of multicellular organisms involves a delicate interplay between genetic and environmental influences. It is often useful to think of developmental systems as integrating available sources of information about current conditions to produce organisms. Genes and inherited physiology provide cues, as does the state of the environment during development. The integration systems themselves are under genetic control and subject to Darwinian selection, so we expect them to evolve to produce organisms that fit well with current ecological (including social) conditions. We argue for the scientific value of this explicitly informational perspective by providing detailed examples of how it can elucidate taxonomically diverse phenomena. We also present a general framework for linking genetic and phenotypic variation from an informational perspective. This application of Darwinian logic at the organismal level can elucidate genetic influences on phenotypic variation in novel and counterintuitive ways.}, } @article {pmid25942385, year = {2015}, author = {McKenney, EA and Williamson, L and Yoder, AD and Rawls, JF and Bilbo, SD and Parker, W}, title = {Alteration of the rat cecal microbiome during colonization with the helminth Hymenolepis diminuta.}, journal = {Gut microbes}, volume = {6}, number = {3}, pages = {182-193}, pmid = {25942385}, issn = {1949-0984}, mesh = {Animals ; Bacteria/*classification/*isolation & purification ; Cecum/*microbiology/*parasitology ; Female ; *Gastrointestinal Microbiome ; Hymenolepis diminuta/*growth & development ; Male ; Rats, Sprague-Dawley ; }, abstract = {The microbiome is now widely recognized as being important in health and disease, and makes up a substantial subset of the biome within the ecosystem of the vertebrate body. At the same time, multicellular, eukaryotic organisms such as helminths are being recognized as an important component of the biome that shaped the evolution of our genes. The absence of these macroscopic organisms during the early development and life of humans in Western culture probably leads to a wide range of human immunological diseases. However, the interaction between the microbiome and macroscopic components of the biome remains poorly characterized. In this study, the microbiome of the cecum in rats colonized for 2 generations with the small intestinal helminth Hymenolepis diminuta was evaluated. The introduction of this benign helminth, which is of considerable therapeutic interest, led to several changes in the cecal microbiome. Most of the changes were within the Firmicutes phylum, involved about 20% of the total bacteria, and generally entailed a shift from Bacilli to Clostridia species in the presence of the helminth. The results point toward ecological relationships between various components of the biome, with the observed shifts in the microbiome suggesting potential mechanisms by which this helminth might exert therapeutic effects.}, } @article {pmid25934012, year = {2015}, author = {Niklas, KJ}, title = {A phyletic perspective on cell growth.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {7}, number = {5}, pages = {}, pmid = {25934012}, issn = {1943-0264}, mesh = {Animals ; *Cell Division ; Cell Size ; Humans ; *Phylogeny ; }, abstract = {Commonalities, as well as lineage-specific differences among bacteria, fungi, plants, and animals, are reviewed in the context of (1) the coordination of cell growth, (2) the flow of mass and energy affecting the physiological status of cells, (3) cytoskeletal dynamics during cell division, and (4) the coordination of cell size in multicellular organs and organisms. A comparative approach reveals that similar mechanisms are used to gauge and regulate cell size and proliferation, and shows that these mechanisms share similar modules to measure cell size, cycle status, competence, and number, as well as ploidy levels, nutrient availability, and other variables affecting cell growth. However, this approach also reveals that these modules often use nonhomologous subsystems when viewed at modular or genomic levels; that is, different lineages have evolved functionally analogous, but not genomically homologous, ways of either sensing or regulating cell size and growth, in much the same way that multicellularity has evolved in different lineages using analogous developmental modules.}, } @article {pmid25926981, year = {2015}, author = {Urban, JM and Foulk, MS and Casella, C and Gerbi, SA}, title = {The hunt for origins of DNA replication in multicellular eukaryotes.}, journal = {F1000prime reports}, volume = {7}, number = {}, pages = {30}, pmid = {25926981}, issn = {2051-7599}, support = {T32 GM007601/GM/NIGMS NIH HHS/United States ; }, abstract = {Origins of DNA replication (ORIs) occur at defined regions in the genome. Although DNA sequence defines the position of ORIs in budding yeast, the factors for ORI specification remain elusive in metazoa. Several methods have been used recently to map ORIs in metazoan genomes with the hope that features for ORI specification might emerge. These methods are reviewed here with analysis of their advantages and shortcomings. The various factors that may influence ORI selection for initiation of DNA replication are discussed.}, } @article {pmid25926819, year = {2015}, author = {Lyon, P}, title = {The cognitive cell: bacterial behavior reconsidered.}, journal = {Frontiers in microbiology}, volume = {6}, number = {}, pages = {264}, pmid = {25926819}, issn = {1664-302X}, abstract = {Research on how bacteria adapt to changing environments underlies the contemporary biological understanding of signal transduction (ST), and ST provides the foundation of the information-processing approach that is the hallmark of the 'cognitive revolution,' which began in the mid-20th century. Yet cognitive scientists largely remain oblivious to research into microbial behavior that might provide insights into problems in their own domains, while microbiologists seem equally unaware of the potential importance of their work to understanding cognitive capacities in multicellular organisms, including vertebrates. Evidence in bacteria for capacities encompassed by the concept of cognition is reviewed. Parallels exist not only at the heuristic level of functional analogue, but also at the level of molecular mechanism, evolution and ecology, which is where fruitful cross-fertilization among disciplines might be found.}, } @article {pmid25923201, year = {2015}, author = {Nam, HJ and Kim, I and Bowie, JU and Kim, S}, title = {Metazoans evolved by taking domains from soluble proteins to expand intercellular communication network.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {9576}, pmid = {25923201}, issn = {2045-2322}, support = {R01 GM063919/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Cell Adhesion/genetics ; Cell Communication/*genetics ; Membrane Proteins/*genetics ; Protein Interaction Domains and Motifs/*genetics ; Protein Structure, Tertiary/*genetics ; Signal Transduction/*genetics ; }, abstract = {A central question in animal evolution is how multicellular animals evolved from unicellular ancestors. We hypothesize that membrane proteins must be key players in the development of multicellularity because they are well positioned to form the cell-cell contacts and to provide the intercellular communication required for the creation of complex organisms. Here we find that a major mechanism for the necessary increase in membrane protein complexity in the transition from non-metazoan to metazoan life was the new incorporation of domains from soluble proteins. The membrane proteins that have incorporated soluble domains in metazoans are enriched in many of the functions unique to multicellular organisms such as cell-cell adhesion, signaling, immune defense and developmental processes. They also show enhanced protein-protein interaction (PPI) network complexity and centrality, suggesting an important role in the cellular diversification found in complex organisms. Our results expose an evolutionary mechanism that contributed to the development of higher life forms.}, } @article {pmid25918398, year = {2015}, author = {Takeuchi, T and Suzuki, M and Fujikake, N and Popiel, HA and Kikuchi, H and Futaki, S and Wada, K and Nagai, Y}, title = {Intercellular chaperone transmission via exosomes contributes to maintenance of protein homeostasis at the organismal level.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {19}, pages = {E2497-506}, pmid = {25918398}, issn = {1091-6490}, mesh = {Animals ; Animals, Genetically Modified ; Cell Line ; Drosophila ; Drosophila melanogaster ; Exosomes/*metabolism ; HSP40 Heat-Shock Proteins/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; HSP90 Heat-Shock Proteins/metabolism ; Heat-Shock Proteins/metabolism ; Homeostasis ; Mice ; Microscopy, Electron ; Molecular Chaperones/*metabolism ; Neurodegenerative Diseases/pathology ; Peptides/chemistry ; Protein Folding ; Protein Structure, Tertiary ; Signal Transduction ; Transcription, Genetic ; Transfection ; }, abstract = {The heat shock response (HSR), a transcriptional response that up-regulates molecular chaperones upon heat shock, is necessary for cell survival in a stressful environment to maintain protein homeostasis (proteostasis). However, there is accumulating evidence that the HSR does not ubiquitously occur under stress conditions, but largely depends on the cell types. Despite such imbalanced HSR among different cells and tissues, molecular mechanisms by which multicellular organisms maintain their global proteostasis have remained poorly understood. Here, we report that proteostasis can be maintained by molecular chaperones not only in a cell-autonomous manner but also in a non-cell-autonomous manner. We found that elevated expression of molecular chaperones, such as Hsp40 and Hsp70, in a group of cells improves proteostasis in other groups of cells, both in cultured cells and in Drosophila expressing aggregation-prone polyglutamine proteins. We also found that Hsp40, as well as Hsp70 and Hsp90, is physiologically secreted from cells via exosomes, and that the J domain at the N terminus is responsible for its exosome-mediated secretion. Addition of Hsp40/Hsp70-containing exosomes to the culture medium of the polyglutamine-expressing cells results in efficient suppression of inclusion body formation, indicating that molecular chaperones non-cell autonomously improve the protein-folding environment via exosome-mediated transmission. Our study reveals that intercellular chaperone transmission mediated by exosomes is a novel molecular mechanism for non-cell-autonomous maintenance of organismal proteostasis that could functionally compensate for the imbalanced state of the HSR among different cells, and also provides a novel physiological role of exosomes that contributes to maintenance of organismal proteostasis.}, } @article {pmid25917826, year = {2015}, author = {Liu, C and Peng, J and Matzuk, MM and Yao, HH}, title = {Lineage specification of ovarian theca cells requires multicellular interactions via oocyte and granulosa cells.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {6934}, pmid = {25917826}, issn = {2041-1723}, support = {ZIA ES102965-03//Intramural NIH HHS/United States ; R01 HD033438/HD/NICHD NIH HHS/United States ; ZIA ES102965-02//Intramural NIH HHS/United States ; ZIA ES102965-04//Intramural NIH HHS/United States ; Z99 ES999999//Intramural NIH HHS/United States ; ZIA ES102965-01//Intramural NIH HHS/United States ; ES102965/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Cell Lineage ; Female ; Granulosa Cells/metabolism ; Growth Differentiation Factor 9/*metabolism ; Hedgehog Proteins/*metabolism ; Kruppel-Like Transcription Factors/metabolism ; Male ; Mesonephros/cytology ; Mice ; Oocytes/*metabolism ; Organ Culture Techniques ; Ovary/*embryology ; Repressor Proteins/metabolism ; *Theca Cells ; Transcriptome ; WT1 Proteins ; Zinc Finger Protein GLI1 ; }, abstract = {Organogenesis of the ovary is a highly orchestrated process involving multiple lineage determination of ovarian surface epithelium, granulosa cells and theca cells. Although the sources of ovarian surface epithelium and granulosa cells are known, the origin(s) of theca progenitor cells have not been definitively identified. Here we show that theca cells derive from two sources: Wt1(+) cells indigenous to the ovary and Gli1(+) mesenchymal cells that migrate from the mesonephros. These progenitors acquire theca lineage marker Gli1 in response to paracrine signals Desert hedgehog (Dhh) and Indian hedgehog (Ihh) from granulosa cells. Ovaries lacking Dhh/Ihh exhibit theca layer loss, blunted steroid production, arrested folliculogenesis and failure to form corpora lutea. Production of Dhh/Ihh in granulosa cells requires growth differentiation factor 9 (GDF9) from the oocyte. Our studies provide the first genetic evidence for the origins of theca cells and reveal a multicellular interaction critical for the formation of a functional theca.}, } @article {pmid25912359, year = {2015}, author = {Elvitigala, DA and Premachandra, HK and Whang, I and Yeo, SY and Choi, CY and Noh, JK and Lee, J}, title = {Molecular cloning, expression and functional characterization of a teleostan cytokine-induced apoptosis inhibitor from rock bream (Oplegnathus fasciatus).}, journal = {Developmental and comparative immunology}, volume = {52}, number = {1}, pages = {48-57}, doi = {10.1016/j.dci.2015.03.016}, pmid = {25912359}, issn = {1879-0089}, mesh = {Animals ; Apoptosis/genetics ; Base Sequence ; Blood Proteins/metabolism ; Caspase 3/metabolism ; Chemokine CXCL10/genetics/*metabolism ; Cloning, Molecular ; Cypriniformes/genetics/*immunology ; Fish Proteins/genetics/*metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Liver/*physiology ; Molecular Sequence Data ; Phylogeny ; Transcriptome ; }, abstract = {Apoptosis plays a key role in the physiology of multicellular organisms and is regulated by different promoting and inhibitory mechanisms. Cytokine-induced apoptotic inhibitor (CIAPI) was recently identified as a key factor involved in apoptosis inhibition in higher vertebrate lineages. However, most of the CIAPIs of lower vertebrate species are yet to be characterized. Herein, we molecularly characterized a teleostan counterpart of CIAPI from rock bream (Oplegnathus fasciatus), designating as RbCIAPI. The complete coding region of RbCIAPI was consisted of 942 nucleotides encoding a protein of 313 amino acids with a predicted molecular mass of ~33 kDa. RbCIAPI gene exhibited a multi-exonic architecture, consisting 9 exons interrupted by 8 introns. Protein sequence analysis revealed that RbCIAPI shares significant homology with known CIAPI counterparts, and phylogenetic reconstruction confirmed its closer evolutionary relationship with its fish counterparts. Ubiquitous spatial distribution of RbCIAPI was detected in our quantitative real time polymerase chain reaction (qPCR) analysis, where more prominent expression levels were observed in the blood and liver tissues. Moreover, the RbCIAPI basal transcription level was found to be modulated by different bacterial and viral stimuli, which could be plausibly supported by our previous observations on the transcriptional modulation of the caspase 3 counterpart of rock bream (Rbcasp3) in response to the same stimuli. In addition, our in vitro functional assay demonstrated that recombinant RbCIAPI could detectably inhibit the proteolysis activity of recombinant Rbcasp3. Collectively, our preliminary results suggest that RbCIAPI may play an anti-apoptotic role in rock bream physiology, likely by inhibiting the caspase-dependent apoptosis pathway. Therefore, RbCIAPI potentially plays an important role in host immunity by regulating the apoptosis process under pathogenic stress.}, } @article {pmid25911230, year = {2015}, author = {Alzayady, KJ and Sebé-Pedrós, A and Chandrasekhar, R and Wang, L and Ruiz-Trillo, I and Yule, DI}, title = {Tracing the Evolutionary History of Inositol, 1, 4, 5-Trisphosphate Receptor: Insights from Analyses of Capsaspora owczarzaki Ca2+ Release Channel Orthologs.}, journal = {Molecular biology and evolution}, volume = {32}, number = {9}, pages = {2236-2253}, pmid = {25911230}, issn = {1537-1719}, support = {R01 DE014756/DE/NIDCR NIH HHS/United States ; R01 DE019245/DE/NIDCR NIH HHS/United States ; R01-DE14756/DE/NIDCR NIH HHS/United States ; 616960/ERC_/European Research Council/International ; T90 DE021985/DE/NIDCR NIH HHS/United States ; R01-DE19245/DE/NIDCR NIH HHS/United States ; }, mesh = {Adenosine Triphosphate/physiology ; Bacterial Proteins/*genetics ; Calcium Signaling ; Evolution, Molecular ; Gene Expression ; Inositol 1,4,5-Trisphosphate Receptors/*genetics ; Mycoplasma/*genetics ; Phylogeny ; }, abstract = {Cellular Ca(2+) homeostasis is tightly regulated and is pivotal to life. Inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) are the major ion channels that regulate Ca(2+) release from intracellular stores. Although these channels have been extensively investigated in multicellular organisms, an appreciation of their evolution and the biology of orthologs in unicellular organisms is largely lacking. Extensive phylogenetic analyses reveal that the IP3R gene superfamily is ancient and diverged into two subfamilies, IP3R-A and IP3R-B/RyR, at the dawn of Opisthokonta. IP3R-B/RyR further diversified into IP3R-B and RyR at the stem of Filozoa. Subsequent evolution and speciation of Holozoa is associated with duplication of IP3R-A and RyR genes, and loss of IP3R-B in the vertebrate lineages. To gain insight into the properties of IP3R important for the challenges of multicellularity, the IP3R-A and IP3R-B family orthologs were cloned from Capsaspora owczarzaki, a close unicellular relative to Metazoa (designated as CO.IP3R-A and CO.IP3R-B). Both proteins were targeted to the endoplasmic reticulum. However, CO.IP3R-A, but strikingly not CO.IP3R-B, bound IP3, exhibited robust Ca(2+) release activity and associated with mammalian IP3Rs. These data indicate strongly that CO.IP3R-A as an exemplar of ancestral IP3R-A orthologs forms bona fide IP3-gated channels. Notably, however, CO.IP3R-A appears not to be regulated by Ca(2+), ATP or Protein kinase A-phosphorylation. Collectively, our findings explore the origin, conservation, and diversification of IP3R gene families and provide insight into the functionality of ancestral IP3Rs and the added specialization of these proteins in Metazoa.}, } @article {pmid25904926, year = {2015}, author = {Gao, D and Jiang, N and Wing, RA and Jiang, J and Jackson, SA}, title = {Transposons play an important role in the evolution and diversification of centromeres among closely related species.}, journal = {Frontiers in plant science}, volume = {6}, number = {}, pages = {216}, pmid = {25904926}, issn = {1664-462X}, abstract = {Centromeres are important chromosomal regions necessary for eukaryotic cell segregation and replication. Due to high amounts of tandem repeats and transposons, centromeres have been difficult to sequence in most multicellular organisms, thus their sequence structure and evolution are poorly understood. In this study, we analyzed transposons in the centromere 8 (Cen8) from the African cultivated rice (O. glaberrima) and two subspecies of the Asian cultivated rice (O. sativa), indica and japonica. We detected much higher transposon contents (>69%) in centromere regions than in the whole genomes of O. sativa ssp. japonica and O. glaberrima (~35%). We compared the three Cen8s and identified numerous recent insertions of transposons that were frequently organized into multiple-layer nested blocks, similar to nested transposons in maize. Except for the Hopi retrotransposon, all LTR retrotransposons were shared but exhibit different abundances amongst the three Cen8s. Even though a majority of the transposons were located in intergenic regions, some gene-related transposons were found and may be involved in gene diversification. Chromatin immunoprecipitated (ChIP) data analysis revealed that 165 families from both Class I and Class II transposons were found in CENH3-associated chromatin sequences. These results indicate essential roles for transposons in centromeres and that the rapid divergence of the Cen8 sequences between the two cultivated rice species was primarily caused by recent transposon insertions.}, } @article {pmid25903626, year = {2015}, author = {Holland, ND and Holland, LZ and Holland, PW}, title = {Scenarios for the making of vertebrates.}, journal = {Nature}, volume = {520}, number = {7548}, pages = {450-455}, pmid = {25903626}, issn = {1476-4687}, mesh = {Animals ; Annelida/anatomy & histology/classification ; Invertebrates/anatomy & histology/classification ; Models, Biological ; *Phylogeny ; Research ; *Vertebrates/anatomy & histology/classification ; }, abstract = {Over the past 200 years, almost every invertebrate phylum has been proposed as a starting point for evolving vertebrates. Most of these scenarios are outdated, but several are still seriously considered. The short-range transition from ancestral invertebrate chordates (similar to amphioxus and tunicates) to vertebrates is well accepted. However, longer-range transitions leading up to the invertebrate chordates themselves are more controversial. Opinion is divided between the annelid and the enteropneust scenarios, predicting, respectively, a complex or a simple ancestor for bilaterian animals. Deciding between these ideas will be facilitated by further comparative studies of multicellular animals, including enigmatic taxa such as xenacoelomorphs.}, } @article {pmid25902452, year = {2015}, author = {Olovnikov, AM}, title = {Chronographic Theory of Development, Aging, and Origin of Cancer: Role of Chronomeres and Printomeres.}, journal = {Current aging science}, volume = {}, number = {}, pages = {}, pmid = {25902452}, issn = {1874-6128}, abstract = {It is supposed that the development and aging of multicellular animals and humans are controlled by a special form of the clock mechanism - a chronograph. The development of animals and their aging are interconnected by the program of the species lifespan that has been selected in the evolution of each species to fit the resources of its ecological niche. The theory is based on the idea about a controlled loss by the neurons in the brain of hypothetical organelles - chronomeres that represent themselves small DNA molecules, which are amplificates of the segments of chromosomal DNA. A regular mode of the process of chronomere losses by neurons is provided by a pacemaker localized in the pineal gland and activated at least once per lunar month. Neurons, consecutively losing their chronomeres, are organized in the brain in the temporal relay race. Analogues of chronomeres, namely printomeres, are supposed to exist in dividing non-neuronal cells. Printomeres are not involved in a performance of temporal function, instead they are responsible for the maintenance in dividing cells of their memory about the state of differentiation. A critical shortening or loss of a printomere in a dividing cell leads to a cellular senescence, whereas telomere shortening is a bystander of this process. Thus, aging of a multicellular organism is associated with the loss of chronomeres, whereas senescence of dividing cells is associated with the loss of regulatory RNAs encoded by printomeres. If the cells that have lost their printomeres are environmentally forced to divide, they can transform into cancer cells.}, } @article {pmid25901306, year = {2015}, author = {Droser, ML and Gehling, JG}, title = {The advent of animals: The view from the Ediacaran.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {16}, pages = {4865-4870}, pmid = {25901306}, issn = {1091-6490}, mesh = {Animals ; *Biota ; *Fossils ; Movement ; Population Dynamics ; Reproduction ; South Australia ; Time Factors ; }, abstract = {Patterns of origination and evolution of early complex life on this planet are largely interpreted from the fossils of the Precambrian soft-bodied Ediacara Biota. These fossils occur globally and represent a diverse suite of organisms living in marine environments. Although these exceptionally preserved fossil assemblages are typically difficult to reconcile with modern phyla, examination of the morphology, ecology, and taphonomy of these taxa provides keys to their relationships with modern taxa. Within the more than 30 million y range of the Ediacara Biota, fossils of these multicellular organisms demonstrate the advent of mobility, heterotrophy by multicellular animals, skeletonization, sexual reproduction, and the assembly of complex ecosystems, all of which are attributes of modern animals. This approach to these fossils, without the constraint of attempting phylogenetic reconstructions, provides a mechanism for comparing these taxa with both living and extinct animals.}, } @article {pmid25898350, year = {2015}, author = {Ovchinnikov, VY and Afonnikov, DA and Vasiliev, GV and Kashina, EV and Sripa, B and Mordvinov, VA and Katokhin, AV}, title = {Identification of microRNA genes in three opisthorchiids.}, journal = {PLoS neglected tropical diseases}, volume = {9}, number = {4}, pages = {e0003680}, pmid = {25898350}, issn = {1935-2735}, mesh = {Animals ; MicroRNAs/genetics ; Multigene Family ; Opisthorchiasis/parasitology ; Opisthorchis/*genetics ; Polymerase Chain Reaction/methods ; RNA, Helminth/*genetics ; }, abstract = {BACKGROUND: Opisthorchis felineus, O. viverrini, and Clonorchis sinensis (family Opisthorchiidae) are parasitic flatworms that pose a serious threat to humans in some countries and cause opisthorchiasis/clonorchiasis. Chronic disease may lead to a risk of carcinogenesis in the biliary ducts. MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression at post-transcriptional level and are implicated in the regulation of various cellular processes during the parasite- host interplay. However, to date, the miRNAs of opisthorchiid flukes, in particular those essential for maintaining their complex biology and parasitic mode of existence, have not been satisfactorily described.

Using a SOLiD deep sequencing-bioinformatic approach, we identified 43 novel and 18 conserved miRNAs for O. felineus (miracidia, metacercariae and adult worms), 20 novel and 16 conserved miRNAs for O. viverrini (adult worms), and 33 novel and 18 conserved miRNAs for C. sinensis (adult worms). The analysis of the data revealed differences in the expression level of conserved miRNAs among the three species and among three the developmental stages of O. felineus. Analysis of miRNA genes revealed two gene clusters, one cluster-like region and one intronic miRNA in the genome. The presence and structure of the two gene clusters were validated using a PCR-based approach in the three flukes.

CONCLUSIONS: This study represents a comprehensive description of miRNAs in three members of the family Opistorchiidae, significantly expands our knowledge of miRNAs in multicellular parasites and provides a basis for understanding the structural and functional evolution of miRNAs in these metazoan parasites. Results of this study also provides novel resources for deeper understanding the complex parasite biology, for further research on the pathogenesis and molecular events of disease induced by the liver flukes. The present data may also facilitate the development of novel approaches for the prevention and treatment of opisthorchiasis/clonorchiasis.}, } @article {pmid25894589, year = {2015}, author = {van Gestel, J and Vlamakis, H and Kolter, R}, title = {From cell differentiation to cell collectives: Bacillus subtilis uses division of labor to migrate.}, journal = {PLoS biology}, volume = {13}, number = {4}, pages = {e1002141}, pmid = {25894589}, issn = {1545-7885}, support = {R01 GM058213/GM/NIGMS NIH HHS/United States ; GM58213/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacillus subtilis/chemistry/*physiology ; *Cell Differentiation ; *Movement ; Quorum Sensing ; }, abstract = {The organization of cells, emerging from cell-cell interactions, can give rise to collective properties. These properties are adaptive when together cells can face environmental challenges that they separately cannot. One particular challenge that is important for microorganisms is migration. In this study, we show how flagellum-independent migration is driven by the division of labor of two cell types that appear during Bacillus subtilis sliding motility. Cell collectives organize themselves into bundles (called "van Gogh bundles") of tightly aligned cell chains that form filamentous loops at the colony edge. We show, by time-course microscopy, that these loops migrate by pushing themselves away from the colony. The formation of van Gogh bundles depends critically on the synergistic interaction of surfactin-producing and matrix-producing cells. We propose that surfactin-producing cells reduce the friction between cells and their substrate, thereby facilitating matrix-producing cells to form bundles. The folding properties of these bundles determine the rate of colony expansion. Our study illustrates how the simple organization of cells within a community can yield a strong ecological advantage. This is a key factor underlying the diverse origins of multicellularity.}, } @article {pmid25881075, year = {2015}, author = {Kawabe, Y and Schilde, C and Du, Q and Schaap, P}, title = {A conserved signalling pathway for amoebozoan encystation that was co-opted for multicellular development.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {9644}, pmid = {25881075}, issn = {2045-2322}, support = {090276/WT_/Wellcome Trust/United Kingdom ; 100293/WT_/Wellcome Trust/United Kingdom ; 100293Z/12/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; BB/K000799/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adenylyl Cyclases/chemistry/genetics/metabolism ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/chemistry/metabolism ; Dictyostelium/growth & development/*metabolism ; Parasite Encystment ; Phenotype ; Protozoan Proteins/chemistry/genetics/metabolism ; *Signal Transduction ; Stress, Physiological ; }, abstract = {The evolution of multicellularity required novel mechanisms for intercellular communication, but their origin is unclear. Dictyostelium cells exchange signals to position specialized cell types in multicellular spore-bearing structures. These signals activate complex pathways that converge on activation of cAMP-dependent protein kinase (PKA). Genes controlling PKA were detected in the Dictyostelid unicellular ancestors, which like most protists form dormant cysts when experiencing environmental stress. We deleted PKA and the adenylate cyclases AcrA and AcgA, which synthesize cAMP for PKA activation, in the intermediate species Polysphondylium, which can develop into either cysts or into multicellular structures. Loss of PKA prevented multicellular development, but also completely blocked encystation. Loss of AcrA and AcgA, both essential for sporulation in Dictyostelium, did not affect Polysphondylium sporulation, but prevented encystation. We conclude that multicellular cAMP signalling was co-opted from PKA regulation of protist encystation with progressive refunctionalization of pathway components.}, } @article {pmid25876075, year = {2015}, author = {Warren, CR and Kassir, E and Spurlin, J and Martinez, J and Putnam, NH and Farach-Carson, MC}, title = {Evolution of the perlecan/HSPG2 gene and its activation in regenerating Nematostella vectensis.}, journal = {PloS one}, volume = {10}, number = {4}, pages = {e0124578}, pmid = {25876075}, issn = {1932-6203}, support = {P01 CA098912/CA/NCI NIH HHS/United States ; P01CA098912/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Basement Membrane/metabolism/ultrastructure ; Cnidaria/classification/*genetics/metabolism/ultrastructure ; Ctenophora/classification/*genetics/metabolism/ultrastructure ; Evolution, Molecular ; Gene Expression ; Heparan Sulfate Proteoglycans/chemistry/*genetics/metabolism ; Humans ; Models, Genetic ; Molecular Sequence Data ; Phylogeny ; Placozoa/classification/*genetics/metabolism/ultrastructure ; Polymerase Chain Reaction ; Porifera/classification/*genetics/metabolism/ultrastructure ; Regeneration/*genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {The heparan sulfate proteoglycan 2 (HSPG2)/perlecan gene is ancient and conserved in all triploblastic species. Its presence maintains critical cell boundaries in tissue and its large (up to ~900 kDa) modular structure has prompted speculation about the evolutionary origin of the gene. The gene's conservation amongst basal metazoans is unclear. After the recent sequencing of their genomes, the cnidarian Nematostella vectensis and the placozoan Trichoplax adhaerens have become favorite models for studying tissue regeneration and the evolution of multicellularity. More ancient basal metazoan phyla include the poriferan and ctenophore, whose evolutionary relationship has been clarified recently. Our in silico and PCR-based methods indicate that the HSPG2 gene is conserved in both the placozoan and cnidarian genomes, but not in those of the ctenophores and only partly in poriferan genomes. HSPG2 also is absent from published ctenophore and Capsaspora owczarzaki genomes. The gene in T. adhaerens is encoded as two separate but genetically juxtaposed genes that house all of the constituent pieces of the mammalian HSPG2 gene in tandem. These genetic constituents are found in isolated genes of various poriferan species, indicating a possible intronic recombinatory mechanism for assembly of the HSPG2 gene. Perlecan's expression during wound healing and boundary formation is conserved, as expression of the gene was activated during tissue regeneration and reformation of the basement membrane of N. vectensis. These data indicate that the complex HSPG2 gene evolved concurrently in a common ancestor of placozoans, cnidarians and bilaterians, likely along with the development of differentiated cell types separated by acellular matrices, and is activated to reestablish these tissue borders during wound healing.}, } @article {pmid25874475, year = {2015}, author = {Kianianmomeni, A}, title = {Cell-type specific photoreceptors and light signaling pathways in the multicellular green alga Volvox carteri and their potential role in cellular differentiation.}, journal = {Plant signaling & behavior}, volume = {10}, number = {4}, pages = {e1010935}, pmid = {25874475}, issn = {1559-2324}, mesh = {*Cell Differentiation ; *Light Signal Transduction ; Models, Biological ; Organ Specificity ; Photoreceptors, Plant/*metabolism ; Volvox/*cytology/*metabolism ; }, abstract = {The formation of multicellular organisms requires genetically predefined signaling pathways in various cell types. Besides differences in size, energy balance and life time, cell types should be enable to modulate appropriate developmental and adaptive responses in ever-changing surrounding environment. One of the most important environmental cues is light which regulates a variety of physiological and cellular processes. During evolution, diverse light-sensitive proteins, so-called photoreceptors, and corresponding signaling pathways have evolved, in almost all kingdoms of life, to monitor light continuously and adjust their growth and development accordingly. However, considering the fact that different cell types should be enable to trigger distinct light signaling pathways according to their needs, cell-type specific light signaling pathways are required to guarantee cell type-matched modulation of cellular and developmental processes in response to different light signals. The multicellular green alga Volvox carteri, which has only 2 cell types with clear division of labor, possesses cell-type specific photoreceptors and light signaling pathways which allow differential regulation of genes involved in various cellular and metabolic pathways in response to environmental light. The existence of cell-type specific light signaling pathways in multicellular organism like Volvox reflects an early development of cell-type specific signaling mechanisms during evolution to ensure maintenance of differentiation.}, } @article {pmid25873590, year = {2015}, author = {Chen, H and Xing, K and He, X}, title = {The dJ/dS Ratio Test Reveals Hundreds of Novel Putative Cancer Drivers.}, journal = {Molecular biology and evolution}, volume = {32}, number = {8}, pages = {2181-2185}, pmid = {25873590}, issn = {1537-1719}, mesh = {Animals ; *Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; *Genes, Neoplasm ; Humans ; *Models, Genetic ; Neoplasms/*genetics/metabolism ; RNA Splice Sites ; RNA Splicing/genetics ; }, abstract = {Computational tools with a balanced sensitivity and specificity in identification of candidate cancer drivers are highly desired. In this study, we propose a new statistical test, namely the dJ/dS ratio test, to compute the relative mutation rate of exon/intron junction sites (dJ) to synonymous sites (dS); observation of dJ/dS ratio larger than 1 in cancer indicates positive selection for splicing deregulation, a signature of cancer driver genes. Using this method, we analyzed the data from The Cancer Genome Atlas and identified hundreds of novel putative cancer drivers. Interestingly, these genes are highly enriched in biological processes related to the development and maintenance of multicellularity, paralleling a previous finding that cancer evolves back to be unicellular by knocking down the multicellularity-associated genetic network.}, } @article {pmid25867922, year = {2015}, author = {Achim, K and Pettit, JB and Saraiva, LR and Gavriouchkina, D and Larsson, T and Arendt, D and Marioni, JC}, title = {High-throughput spatial mapping of single-cell RNA-seq data to tissue of origin.}, journal = {Nature biotechnology}, volume = {33}, number = {5}, pages = {503-509}, pmid = {25867922}, issn = {1546-1696}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Gene Expression Regulation, Developmental ; High-Throughput Nucleotide Sequencing/*methods ; Organ Specificity/genetics ; Polychaeta/*genetics/growth & development ; Single-Cell Analysis/*methods ; Transcriptome/genetics ; }, abstract = {Understanding cell type identity in a multicellular organism requires the integration of gene expression profiles from individual cells with their spatial location in a particular tissue. Current technologies allow whole-transcriptome sequencing of spatially identified cells but lack the throughput needed to characterize complex tissues. Here we present a high-throughput method to identify the spatial origin of cells assayed by single-cell RNA-sequencing within a tissue of interest. Our approach is based on comparing complete, specificity-weighted mRNA profiles of a cell with positional gene expression profiles derived from a gene expression atlas. We show that this method allocates cells to precise locations in the brain of the marine annelid Platynereis dumerilii with a success rate of 81%. Our method is applicable to any system that has a reference gene expression database of sufficiently high resolution.}, } @article {pmid25855805, year = {2015}, author = {Školáková, P and Foldynová-Trantírková, S and Bednářová, K and Fiala, R and Vorlíčková, M and Trantírek, L}, title = {Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA.}, journal = {Nucleic acids research}, volume = {43}, number = {9}, pages = {4733-4745}, pmid = {25855805}, issn = {1362-4962}, mesh = {Animals ; Caenorhabditis elegans/genetics ; DNA/*chemistry ; *Evolution, Molecular ; Humans ; Nucleic Acid Conformation ; Telomere/*chemistry ; }, abstract = {There are two basic mechanisms that are associated with the maintenance of the telomere length, which endows cancer cells with unlimited proliferative potential. One mechanism, referred to as alternative lengthening of telomeres (ALT), accounts for approximately 10-15% of all human cancers. Tumours engaged in the ALT pathway are characterised by the presence of the single stranded 5'-C-rich telomeric overhang (C-overhang). This recently identified hallmark of ALT cancers distinguishes them from healthy tissues and renders the C-overhang as a clear target for anticancer therapy. We analysed structures of the 5'-C-rich and 3'-G-rich telomeric overhangs from human and Caenorhabditis elegans, the recently established multicellular in vivo model of ALT tumours. We show that the telomeric DNA from C. elegans and humans forms fundamentally different secondary structures. The unique structural characteristics of C. elegans telomeric DNA that are distinct not only from those of humans but also from those of other multicellular eukaryotes allowed us to identify evolutionarily conserved properties of telomeric DNA. Differences in structural organisation of the telomeric DNA between the C. elegans and human impose limitations on the use of the C. elegans as an ALT tumour model.}, } @article {pmid25850291, year = {2014}, author = {Kogan, GL and Gvozdev, VA}, title = {[Multifunctional protein complex NAC (nascent polypeptide associated complex].}, journal = {Molekuliarnaia biologiia}, volume = {48}, number = {2}, pages = {223-231}, pmid = {25850291}, issn = {0026-8984}, mesh = {Caspase 3/genetics/metabolism ; Eukaryotic Cells/cytology/*metabolism ; Evolution, Molecular ; *Gene Expression Regulation ; Humans ; Molecular Chaperones/chemistry/*genetics/metabolism ; Protein Binding ; *Protein Biosynthesis ; Protein Folding ; Protein Multimerization ; Protein Stability ; Protein Subunits/chemistry/*genetics/metabolism ; Ribosomes/genetics/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Signal Transduction ; }, abstract = {The functions of the evolutionary conservative complex NAC (Nascent polypepetide Associated Complex) and its subunits are discussed. The heterodimeric NAC protein contains alpha- and beta-subunits and is found to be reversibly bounded to the ribosome in all eukaryotes, from yeast to humans. NAC contacts the nascent polypeptide and protects it from proteolysis. NAC participates in polypeptide chain folding and modulates protein secretion and transmembrane protein formation. Mutations and deletions of genes, encoding NAC subunits are lethal in early development of multicellular eukaryotes. NAC is involved in the ribosome biogenesis. The beta-subunit interacts with caspase-3 and may be involved in the regulation of the apoptotic pathway. The variants of NAC proteins can be considered as chaperone complexes, involved in the response of the cell and the organism to stress factors, as well as regulators of apoptosis. The genes encoding beta-subunits are rapidly evolved, their duplications cause the formation of tissue specific beta-subunit variants with a different number of putative caspase cleavage sites. The homodimer of alpha-subunits is shown to be the RNA/DNA binding protein and acts as a transcriptional cofactor. The diversity in the functioning of NAC is a prime example of a protein that performs a variety of biological functions (moonlighting protein).}, } @article {pmid25847029, year = {2015}, author = {Yue, JX and Li, KL and Yu, JK}, title = {Discovery of germline-related genes in Cephalochordate amphioxus: A genome wide survey using genome annotation and transcriptome data.}, journal = {Marine genomics}, volume = {24 Pt 2}, number = {}, pages = {147-157}, doi = {10.1016/j.margen.2015.03.010}, pmid = {25847029}, issn = {1876-7478}, mesh = {Animals ; DNA, Complementary ; Evolution, Molecular ; Expressed Sequence Tags ; Gene Expression Regulation, Developmental/physiology ; *Genome ; *Genome-Wide Association Study ; Lancelets/*genetics ; Species Specificity ; *Transcriptome ; }, abstract = {The generation of germline cells is a critical process in the reproduction of multicellular organisms. Studies in animal models have identified a common repertoire of genes that play essential roles in primordial germ cell (PGC) formation. However, comparative studies also indicate that the timing and regulation of this core genetic program vary considerably in different animals, raising the intriguing questions regarding the evolution of PGC developmental mechanisms in metazoans. Cephalochordates (commonly called amphioxus or lancelets) represent one of the invertebrate chordate groups and can provide important information about the evolution of developmental mechanisms in the chordate lineage. In this study, we used genome and transcriptome data to identify germline-related genes in two distantly related cephalochordate species, Branchiostoma floridae and Asymmetron lucayanum. Branchiostoma and Asymmetron diverged more than 120 MYA, and the most conspicuous difference between them is their gonadal morphology. We used important germline developmental genes in several model animals to search the amphioxus genome and transcriptome dataset for conserved homologs. We also annotated the assembled transcriptome data using Gene Ontology (GO) terms to facilitate the discovery of putative genes associated with germ cell development and reproductive functions in amphioxus. We further confirmed the expression of 14 genes in developing oocytes or mature eggs using whole mount in situ hybridization, suggesting their potential functions in amphioxus germ cell development. The results of this global survey provide a useful resource for testing potential functions of candidate germline-related genes in cephalochordates and for investigating differences in gonad developmental mechanisms between Branchiostoma and Asymmetron species.}, } @article {pmid25845915, year = {2015}, author = {Rehorek, SJ and Cunningham, J and Bruening, AE and Johnson, JL and Bhatnagar, KP and Smith, TD and Hillenius, WJ}, title = {Development of the nasolacrimal apparatus in the Mongolian gerbil (Meriones unguiculatus), with notes on network topology and function.}, journal = {Journal of morphology}, volume = {276}, number = {9}, pages = {1005-1024}, doi = {10.1002/jmor.20393}, pmid = {25845915}, issn = {1097-4687}, mesh = {Animals ; Gerbillinae/*embryology/growth & development ; Head/embryology/growth & development ; Vomeronasal Organ/*growth & development/physiology ; }, abstract = {The nasolacrimal apparatus (NLA) is a multicomponent functional system comprised of multiple orbital glands (up to four larger multicellular exocrine structures), a nasal chemosensory structure (vomeronasal organ: VNO), and a connecting duct (nasolacrimal duct: NLD). Although this system has been described in all tetrapod vertebrate lineages, albeit not always with all three main components present, considerably less is known about its ontogeny. The Mongolian gerbil (Meriones unguiculatus) is a common lab rodent in which the individual components of the adult NLA have been well studied, but as yet nothing is known about the ontogeny of the NLA. In this study, serial sections of 15 fetal and three adult Mongolian gerbil heads show that the development of the NLA falls into three fetal stages: inception (origin of all features), elongation (lengthening of all features), and expansion (widening of all features). No postnatal or juvenile specimens were observed in this study, but considerable growth evidently occurs before the final adult condition is reached. The development of the orbital glands and the VNO in the Mongolian gerbil is largely consistent with those in other mammals, despite a slight nomenclatural conundrum for the anterior orbital glands. However, the Mongolian gerbil NLD follows a more circuitous route than in other tetrapods, due mainly to the convoluted arrangement of the narial cartilages, the development of a pair of enlarged incisors as well as an enlarged infraorbital foramen. The impact of these associated features on the ontogeny and phylogeny of the NLA could be examined through the approach of network science. This approach allows for the incorporation of adaptations to specific lifestyles as potential explanations for the variation observed in the NLA across different tetrapod clades.}, } @article {pmid25838283, year = {2015}, author = {Szathmáry, E}, title = {Toward major evolutionary transitions theory 2.0.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {33}, pages = {10104-10111}, pmid = {25838283}, issn = {1091-6490}, support = {294332/ERC_/European Research Council/International ; }, mesh = {Animals ; Bacteria/genetics ; *Biological Evolution ; Cultural Characteristics ; Ecosystem ; Eukaryotic Cells/cytology ; Female ; Gene Transfer, Horizontal ; Genetic Code ; Humans ; Language ; Male ; Mitochondria/genetics ; Organelle Biogenesis ; Phagocytosis ; Phylogeny ; Plastids/genetics ; Reproducibility of Results ; Stochastic Processes ; }, abstract = {The impressive body of work on the major evolutionary transitions in the last 20 y calls for a reconstruction of the theory although a 2D account (evolution of informational systems and transitions in individuality) remains. Significant advances include the concept of fraternal and egalitarian transitions (lower-level units like and unlike, respectively). Multilevel selection, first without, then with, the collectives in focus is an important explanatory mechanism. Transitions are decomposed into phases of origin, maintenance, and transformation (i.e., further evolution) of the higher level units, which helps reduce the number of transitions in the revised list by two so that it is less top-heavy. After the transition, units show strong cooperation and very limited realized conflict. The origins of cells, the emergence of the genetic code and translation, the evolution of the eukaryotic cell, multicellularity, and the origin of human groups with language are reconsidered in some detail in the light of new data and considerations. Arguments are given why sex is not in the revised list as a separate transition. Some of the transitions can be recursive (e.g., plastids, multicellularity) or limited (transitions that share the usual features of major transitions without a massive phylogenetic impact, such as the micro- and macronuclei in ciliates). During transitions, new units of reproduction emerge, and establishment of such units requires high fidelity of reproduction (as opposed to mere replication).}, } @article {pmid25825767, year = {2015}, author = {Karkar, S and Facchinelli, F and Price, DC and Weber, AP and Bhattacharya, D}, title = {Metabolic connectivity as a driver of host and endosymbiont integration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {33}, pages = {10208-10215}, pmid = {25825767}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/metabolism ; *Biological Evolution ; Biological Transport ; Computational Biology ; Evolution, Molecular ; Oxidation-Reduction ; Photosynthesis ; Phylogeny ; Plastids/*genetics/metabolism ; Rhodophyta/metabolism ; Symbiosis/*genetics ; }, abstract = {The origin of oxygenic photosynthesis in the Archaeplastida common ancestor was foundational for the evolution of multicellular life. It is very likely that the primary endosymbiosis that explains plastid origin relied initially on the establishment of a metabolic connection between the host cell and captured cyanobacterium. We posit that these connections were derived primarily from existing host-derived components. To test this idea, we used phylogenomic and network analysis to infer the phylogenetic origin and evolutionary history of 37 validated plastid innermost membrane (permeome) metabolite transporters from the model plant Arabidopsis thaliana. Our results show that 57% of these transporter genes are of eukaryotic origin and that the captured cyanobacterium made a relatively minor (albeit important) contribution to the process. We also tested the hypothesis that the bacterium-derived hexose-phosphate transporter UhpC might have been the primordial sugar transporter in the Archaeplastida ancestor. Bioinformatic and protein localization studies demonstrate that this protein in the extremophilic red algae Galdieria sulphuraria and Cyanidioschyzon merolae are plastid targeted. Given this protein is also localized in plastids in the glaucophyte alga Cyanophora paradoxa, we suggest it played a crucial role in early plastid endosymbiosis by connecting the endosymbiont and host carbon storage networks. In summary, our work significantly advances understanding of plastid integration and favors a host-centric view of endosymbiosis. Under this view, nuclear genes of either eukaryotic or bacterial (noncyanobacterial) origin provided key elements of the toolkit needed for establishing metabolic connections in the primordial Archaeplastida lineage.}, } @article {pmid25816286, year = {2015}, author = {Torres-Sánchez, A and Gómez-Gardeñes, J and Falo, F}, title = {An integrative approach for modeling and simulation of heterocyst pattern formation in cyanobacteria filaments.}, journal = {PLoS computational biology}, volume = {11}, number = {3}, pages = {e1004129}, pmid = {25816286}, issn = {1553-7358}, mesh = {Cell Differentiation ; Computational Biology/*methods ; Cyanobacteria/*physiology ; *Models, Biological ; }, abstract = {Heterocyst differentiation in cyanobacteria filaments is one of the simplest examples of cellular differentiation and pattern formation in multicellular organisms. Despite of the many experimental studies addressing the evolution and sustainment of heterocyst patterns and the knowledge of the genetic circuit underlying the behavior of single cyanobacterium under nitrogen deprivation, there is still a theoretical gap connecting these two macroscopic and microscopic processes. As an attempt to shed light on this issue, here we explore heterocyst differentiation under the paradigm of systems biology. This framework allows us to formulate the essential dynamical ingredients of the genetic circuit of a single cyanobacterium into a set of differential equations describing the time evolution of the concentrations of the relevant molecular products. As a result, we are able to study the behavior of a single cyanobacterium under different external conditions, emulating nitrogen deprivation, and simulate the dynamics of cyanobacteria filaments by coupling their respective genetic circuits via molecular diffusion. These two ingredients allow us to understand the principles by which heterocyst patterns can be generated and sustained. In particular, our results point out that, by including both diffusion and noisy external conditions in the computational model, it is possible to reproduce the main features of the formation and sustainment of heterocyst patterns in cyanobacteria filaments as observed experimentally. Finally, we discuss the validity and possible improvements of the model.}, } @article {pmid25815986, year = {2015}, author = {Chantranupong, L and Wolfson, RL and Sabatini, DM}, title = {Nutrient-sensing mechanisms across evolution.}, journal = {Cell}, volume = {161}, number = {1}, pages = {67-83}, pmid = {25815986}, issn = {1097-4172}, support = {R01 AI047389/AI/NIAID NIH HHS/United States ; R01 CA103866/CA/NCI NIH HHS/United States ; T32 GM007287/GM/NIGMS NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; F31 CA180271/CA/NCI NIH HHS/United States ; R37 AI047389/AI/NIAID NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; AI47389/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/genetics/*metabolism ; Biological Evolution ; Eukaryota/genetics/metabolism ; Food ; *Signal Transduction ; }, abstract = {For organisms to coordinate their growth and development with nutrient availability, they must be able to sense nutrient levels in their environment. Here, we review select nutrient-sensing mechanisms in a few diverse organisms. We discuss how these mechanisms reflect the nutrient requirements of specific species and how they have adapted to the emergence of multicellularity in eukaryotes.}, } @article {pmid25814207, year = {2015}, author = {Rashidi, A and Shelton, DE and Michod, RE}, title = {A Darwinian approach to the origin of life cycles with group properties.}, journal = {Theoretical population biology}, volume = {102}, number = {}, pages = {76-84}, doi = {10.1016/j.tpb.2015.03.003}, pmid = {25814207}, issn = {1096-0325}, mesh = {Animals ; *Biological Evolution ; Body Size ; Cell Growth Processes ; Genotype ; Life Cycle Stages/*physiology ; Models, Theoretical ; Mutation/physiology ; *Origin of Life ; Selection, Genetic ; }, abstract = {A selective explanation for the evolution of multicellular organisms from unicellular ones requires knowledge of both selective pressures and factors affecting the response to selection. Understanding the response to selection is particularly challenging in the case of evolutionary transitions in individuality, because these transitions involve a shift in the very units of selection. We develop a conceptual framework in which three fundamental processes (growth, division, and splitting) are the scaffold for unicellular and multicellular life cycles alike. We (i) enumerate the possible ways in which these processes can be linked to create more complex life cycles, (ii) introduce three genes based on growth, division and splitting that, acting in concert, determine the architecture of the life cycles, and finally, (iii) study the evolution of the simplest five life cycles using a heuristic model of coupled ordinary differential equations in which mutations are allowed in the three genes. We demonstrate how changes in the regulation of three fundamental aspects of colonial form (cell size, colony size, and colony cell number) could lead unicellular life cycles to evolve into primitive multicellular life cycles with group properties. One interesting prediction of the model is that selection generally favors cycles with group level properties when intermediate body size is associated with lowest mortality. That is, a universal requirement for the evolution of group cycles in the model is that the size-mortality curve be U-shaped. Furthermore, growth must decelerate with size.}, } @article {pmid25786324, year = {2014}, author = {Maryanovich, AT}, title = {[Phylogeny of peptide regulation: the beginning].}, journal = {Zhurnal evoliutsionnoi biokhimii i fiziologii}, volume = {50}, number = {5}, pages = {402-410}, pmid = {25786324}, issn = {0044-4529}, mesh = {Animals ; *Autocrine Communication ; *Evolution, Molecular ; Peptide Hormones/biosynthesis/*genetics/metabolism ; *Phylogeny ; Proteolysis ; }, abstract = {Analyzing existing literature sources and his own experimental data, the author has concluded that (i) regulatory peptides arise solely as a result of cleavage of protein precursors, but not by non-ribosomal synthesis; (ii) the peptide regulation of physiological functions emerged as a part of autocrine regulation system almost simultaneously with life itself; peptide paracrine regulation appeared in the colonial prokaryotes, and peptide endocrine regulation in the multicellular eukaryotes; (iii) the regulatory peptides and their receptors could occur either sequentially (in any order) or simultaneously; (iv) conservatism of the primary structure of regulatory peptides is not significantly different from that of proteins; (v) the regulatory peptides are presented in the most evolutionarily ancient species wider than specialists think.}, } @article {pmid25784475, year = {2015}, author = {Haig, D}, title = {Coleochaete and the origin of sporophytes.}, journal = {American journal of botany}, volume = {102}, number = {3}, pages = {417-422}, doi = {10.3732/ajb.1400526}, pmid = {25784475}, issn = {1537-2197}, mesh = {*Biological Evolution ; *Cell Division ; Charophyceae/*growth & development ; Models, Biological ; Ploidies ; Reproduction ; }, abstract = {UNLABELLED: •

PREMISE OF THE STUDY: Zygotes of Coleochaete are provisioned by the maternal thallus before undergoing 3-5 rounds of division to produce 8-32 zoospores. An understanding of the selective forces favoring postzygotic divisions would be relevant not only to the interpretation of Coleochaete life history but also to the origin of a multicellular diploid phase in embryophytes.•

METHODS: Simple optimization models are developed of the number of zygotes per maternal thallus and number of zoospores per zygote.•

KEY RESULTS: Zygotic mitosis is favored once zygotic size exceeds a threshold, but natural selection usually promotes investment in additional zygotes before zygotes reach this threshold. Factors that favor production of fewer, larger zygotes include multiple paternity, low fecundity, and accessory costs of zygote production. Such factors can result in zygotes exceeding the size at which zygotic mitosis becomes profitable.•

CONCLUSIONS: Coleochaete may possess large zygotes that undergo multiple fission because of accessory costs associated with matrotrophy, including costs of cortical cells and unfertilized oogonia. The unpredictability of fertilization on land is proposed to have increased accessory costs from unfertilized ova and, as a consequence, to have favored the production of larger zygotes that underwent postzygotic division to produce diploid sporophytes.}, } @article {pmid25782278, year = {2014}, author = {Zhuravleva, AIu}, title = {[Early history of the Metazoa--a palaeontologist's viewpoint].}, journal = {Zhurnal obshchei biologii}, volume = {75}, number = {6}, pages = {411-465}, pmid = {25782278}, issn = {0044-4596}, mesh = {Animals ; *Biological Evolution ; Paleontology ; }, abstract = {The molecular biology success, which became influential for a revision of principal views on the relationships and evolutionary pathways of major groups ("phyla") of multicellular animals, were much more appreciated by palaeontologists rather than by neontologists. This is not surprising because this is the fossil record that serves as a firm test for molecular biological hypotheses. The fossil record indicates that the different "phyla" united nowadays into the Ecdysozoa, namely, arthropods, onychophorans, tardigrades, priapulids, nematomorphs, comprise a number of transitional forms having become extinct already in the early Palaeozoic. The very appearance of those organisms fits entirely to hypothetical ancestral forms which have to exist in accordance with some data on ontogeny. There are no even tentative intermediates between arthropods and annelids in the fossil record. The oldest Deuterostomia, which is the only branch of the Bilateria being agreed upon by all the biological disciplines, allow us, although in less details, to present their early history and point to agile bilaterally-symmetrical forms at the dawn of chordates, hemichordates, and echinoderms. The interpretation of the early history of the Lophotrochozoa is even more difficult because in comparison to other bilaterians, their oldest fossils are preserved as mineralized skeletons only. However, a unity of microstructures of molluscs, brachiopods, and bryozoans, absent in other metazoans, is indicative of the presence of close relatives among different earliest lophotrochozoans some of which are sedentary filterers while others are motile epibenthic detritophages. In the aggregate, modern data of molecular biology, palaeontology, and comparative embryology/morphology, having got a second wind with an introduction of new microscopy techniques, imply that the suggestion of a planktotrophic gastraea-like common ancestor is the least possible among diverse suggestions on the Metazoa origins. The common ancestor of the Bilateria had to be a motile epibenthic animal and the explosive metazoan diversification embracing the late Ediacaran--early Cambrian interval (c. 40 Ma) was probably a real event, which was predated by a long (c. a billion years) assembly of the metazoan genome within unicellular and colonial common ancestors of the Opisthokonta and even the Unikonta as a whole.}, } @article {pmid25778404, year = {2015}, author = {Selvan, N and Mariappa, D and van den Toorn, HW and Heck, AJ and Ferenbach, AT and van Aalten, DM}, title = {The Early Metazoan Trichoplax adhaerens Possesses a Functional O-GlcNAc System.}, journal = {The Journal of biological chemistry}, volume = {290}, number = {19}, pages = {11969-11982}, pmid = {25778404}, issn = {1083-351X}, support = {WT087590MA/WT_/Wellcome Trust/United Kingdom ; 087590/WT_/Wellcome Trust/United Kingdom ; G0900138/MRC_/Medical Research Council/United Kingdom ; MR/M004139/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Acetylglucosamine/chemistry ; Animals ; Animals, Genetically Modified ; Cell Nucleus/enzymology ; Crosses, Genetic ; Cytoplasm/enzymology ; Drosophila melanogaster ; HEK293 Cells ; Humans ; Inhibitory Concentration 50 ; Molecular Sequence Data ; N-Acetylglucosaminyltransferases/*metabolism ; Placozoa/*enzymology ; Protein Processing, Post-Translational ; Protein Structure, Tertiary ; RNA Interference ; Signal Transduction ; }, abstract = {Protein O-GlcNAcylation is a reversible post-translational signaling modification of nucleocytoplasmic proteins that is essential for embryonic development in bilateria. In a search for a reductionist model to study O-GlcNAc signaling, we discovered the presence of functional O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), and nucleocytoplasmic protein O-GlcNAcylation in the most basal extant animal, the placozoan Trichoplax adhaerens. We show via enzymatic characterization of Trichoplax OGT/OGA and genetic rescue experiments in Drosophila melanogaster that these proteins possess activities/functions similar to their bilaterian counterparts. The acquisition of O-GlcNAc signaling by metazoa may have facilitated the rapid and complex signaling mechanisms required for the evolution of multicellular organisms.}, } @article {pmid25775948, year = {2015}, author = {Wu, H and Shang, LQ and Chen, RL and Yang, SM and Wang, SL and Wang, J and Sun, G}, title = {Significance of Trask protein interactions in brain metastatic cohorts of lung cancers.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {36}, number = {6}, pages = {4181-4187}, pmid = {25775948}, issn = {1423-0380}, mesh = {Adenocarcinoma/*genetics/pathology ; Antigens, CD/*genetics/metabolism ; Antigens, Neoplasm ; Brain Neoplasms/*genetics/pathology/secondary ; Calcium/metabolism ; Calcium Channels/genetics/metabolism ; Cell Adhesion/genetics ; Cell Adhesion Molecules/*genetics/metabolism ; Cell Line, Tumor ; Humans ; Membrane Proteins/genetics/metabolism ; Neoplasm Proteins/*genetics/metabolism ; ORAI1 Protein ; Phosphorylation ; Protein Interaction Maps ; Small Cell Lung Carcinoma/*genetics/pathology ; Stromal Interaction Molecule 1 ; src-Family Kinases/genetics/metabolism ; }, abstract = {A class of adhesion protein that occurs in the membrane with both extracellular and intracellular domain and play vital role in maintaining multicellularity is TRASK, also called CUB-domain containing protein1, CD318 (CDCP1). Specifically, in the current study, documented aggressive grades of lung cancers and distant metastatic tissues were examined for protein interactions of Trask and compared with lung cancer variants in situ. The intracellular domain of Trask has the ability to undergo tyrosine phosphorylation and thereafter undergo increased genomic expression, as well as interact with cytoskeletal proteins in the cell periphery and other local signal transduction machinery to induce invadopodia formation and distant metastasis. We incorporated proximity ligation assay to examine protein interactions of Trask in metastatic lung cancer tissues and compare with advanced and low-grade lung cancers restricted to the primary site of origins. Here, we provide direct evidence that activated Trask, which is a phosphorylated form, binds with cytoskeletal proteins actin and spectrin. These interactions were not seen in locally growing lung cancer and cancer in situ. These interactions may be responsible for invadopodia formation and breaking free from a multicellular environment. Functional studies demonstrated interaction between Trask and the STOCs Orai1 and Stim1. Calcium release from internal stores was highest in metastatic lung cancers, suggesting this mechanism as an initial stimulus for the cells to respond chaotically to external growth factor stimulation, especially in aggressive metastatic variants of lung cancers. Recently, inhibitors of STOCs have been identified, and preclinical evidence may be obtained whether these drugs may be of benefit in preventing the deadly consequences of lung cancer.}, } @article {pmid25775860, year = {2014}, author = {Ivanova, VP and Krivchenko, AI}, title = {[A current viewpoint on structure and evolution of collagens. II. The fibril-associated collagens with interrupted triple helices].}, journal = {Zhurnal evoliutsionnoi biokhimii i fiziologii}, volume = {50}, number = {4}, pages = {245-254}, pmid = {25775860}, issn = {0044-4529}, mesh = {Animals ; *Evolution, Molecular ; Fibril-Associated Collagens/*chemistry/genetics/metabolism ; Humans ; Protein Structure, Tertiary ; }, abstract = {Fibril-associated collagens with interrupted triple helices (FACITs) form one of the subfamilies of collagen family. Being minor components of connective tissues in multicellular animals, FACITs play an important role in structurization of extracellular matrix whose peculiarities determine differences among tissues. FACITs take part in regulation of the sizes of banded collagen fibrils and are also a link between diverse components of extracellular matrix and cells in different tissues. The functional characteristics of FACIT molecules are determined by peculiarities of α-chain structure (interruptions in collagenous domains and module structure of N-terminal noncollagenous regions), trimeric molecules (trimerization domains), and supramolecular assemblies (mainly, association with banded fibrils and inability to form homopolymeric suprastructural aggregates). The evolution of FACITs is also discussed. A hypothetical model of structural changes leading to formation of FACIT subfamily is propounded.}, } @article {pmid25772340, year = {2015}, author = {Levin, SR and Brock, DA and Queller, DC and Strassmann, JE}, title = {Concurrent coevolution of intra-organismal cheaters and resisters.}, journal = {Journal of evolutionary biology}, volume = {28}, number = {4}, pages = {756-765}, doi = {10.1111/jeb.12618}, pmid = {25772340}, issn = {1420-9101}, mesh = {*Biological Evolution ; Dictyostelium/*physiology ; }, abstract = {The evolution of multicellularity is a major transition that is not yet fully understood. Specifically, we do not know whether there are any mechanisms by which multicellularity can be maintained without a single-cell bottleneck or other relatedness-enhancing mechanisms. Under low relatedness, cheaters can evolve that benefit from the altruistic behaviour of others without themselves sacrificing. If these are obligate cheaters, incapable of cooperating, their spread can lead to the demise of multicellularity. One possibility, however, is that cooperators can evolve resistance to cheaters. We tested this idea in a facultatively multicellular social amoeba, Dictyostelium discoideum. This amoeba usually exists as a single cell but, when stressed, thousands of cells aggregate to form a multicellular organism in which some of the cells sacrifice for the good of others. We used lineages that had undergone experimental evolution at very low relatedness, during which time obligate cheaters evolved. Unlike earlier experiments, which found resistance to cheaters that were prevented from evolving, we competed cheaters and noncheaters that evolved together, and cheaters with their ancestors. We found that noncheaters can evolve resistance to cheating before cheating sweeps through the population and multicellularity is lost. Our results provide insight into cheater-resister coevolutionary dynamics, in turn providing experimental evidence for the maintenance of at least a simple form of multicellularity by means other than high relatedness.}, } @article {pmid25765996, year = {2015}, author = {Ross, CR and DeFelice, DS and Hunt, GJ and Ihle, KE and Amdam, GV and Rueppell, O}, title = {Genomic correlates of recombination rate and its variability across eight recombination maps in the western honey bee (Apis mellifera L.).}, journal = {BMC genomics}, volume = {16}, number = {1}, pages = {107}, pmid = {25765996}, issn = {1471-2164}, support = {R15 GM102753/GM/NIGMS NIH HHS/United States ; R15GM102753/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Composition/genetics ; Bees/*genetics ; Chromosome Mapping ; Chromosome Segregation/genetics ; Chromosomes/genetics ; *Evolution, Molecular ; Genome, Insect/genetics ; Meiosis/*genetics ; *Recombination, Genetic ; }, abstract = {BACKGROUND: Meiotic recombination has traditionally been explained based on the structural requirement to stabilize homologous chromosome pairs to ensure their proper meiotic segregation. Competing hypotheses seek to explain the emerging findings of significant heterogeneity in recombination rates within and between genomes, but intraspecific comparisons of genome-wide recombination patterns are rare. The honey bee (Apis mellifera) exhibits the highest rate of genomic recombination among multicellular animals with about five cross-over events per chromatid.

RESULTS: Here, we present a comparative analysis of recombination rates across eight genetic linkage maps of the honey bee genome to investigate which genomic sequence features are correlated with recombination rate and with its variation across the eight data sets, ranging in average marker spacing ranging from 1 Mbp to 120 kbp. Overall, we found that GC content explained best the variation in local recombination rate along chromosomes at the analyzed 100 kbp scale. In contrast, variation among the different maps was correlated to the abundance of microsatellites and several specific tri- and tetra-nucleotides.

CONCLUSIONS: The combined evidence from eight medium-scale recombination maps of the honey bee genome suggests that recombination rate variation in this highly recombining genome might be due to the DNA configuration instead of distinct sequence motifs. However, more fine-scale analyses are needed. The empirical basis of eight differing genetic maps allowed for robust conclusions about the correlates of the local recombination rates and enabled the study of the relation between DNA features and variability in local recombination rates, which is particularly relevant in the honey bee genome with its exceptionally high recombination rate.}, } @article {pmid25758444, year = {2015}, author = {Urushihara, H and Kuwayama, H and Fukuhara, K and Itoh, T and Kagoshima, H and Shin-I, T and Toyoda, A and Ohishi, K and Taniguchi, T and Noguchi, H and Kuroki, Y and Hata, T and Uchi, K and Mohri, K and King, JS and Insall, RH and Kohara, Y and Fujiyama, A}, title = {Comparative genome and transcriptome analyses of the social amoeba Acytostelium subglobosum that accomplishes multicellular development without germ-soma differentiation.}, journal = {BMC genomics}, volume = {16}, number = {1}, pages = {80}, pmid = {25758444}, issn = {1471-2164}, mesh = {Amoeba/*genetics/growth & development ; Cell Differentiation/genetics ; Gene Expression ; Gene Expression Profiling ; *Genome, Protozoan ; Phylogeny ; Transcriptome/*genetics ; }, abstract = {BACKGROUND: Social amoebae are lower eukaryotes that inhabit the soil. They are characterized by the construction of a starvation-induced multicellular fruiting body with a spore ball and supportive stalk. In most species, the stalk is filled with motile stalk cells, as represented by the model organism Dictyostelium discoideum, whose developmental mechanisms have been well characterized. However, in the genus Acytostelium, the stalk is acellular and all aggregated cells become spores. Phylogenetic analyses have shown that it is not an ancestral genus but has lost the ability to undergo cell differentiation.

RESULTS: We performed genome and transcriptome analyses of Acytostelium subglobosum and compared our findings to other available dictyostelid genome data. Although A. subglobosum adopts a qualitatively different developmental program from other dictyostelids, its gene repertoire was largely conserved. Yet, families of polyketide synthase and extracellular matrix proteins have not expanded and a serine protease and ABC transporter B family gene, tagA, and a few other developmental genes are missing in the A. subglobosum lineage. Temporal gene expression patterns are astonishingly dissimilar from those of D. discoideum, and only a limited fraction of the ortholog pairs shared the same expression patterns, so that some signaling cascades for development seem to be disabled in A. subglobosum.

CONCLUSIONS: The absence of the ability to undergo cell differentiation in Acytostelium is accompanied by a small change in coding potential and extensive alterations in gene expression patterns.}, } @article {pmid25751731, year = {2015}, author = {Chen, H and Lin, F and Xing, K and He, X}, title = {The reverse evolution from multicellularity to unicellularity during carcinogenesis.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {6367}, doi = {10.1038/ncomms7367}, pmid = {25751731}, issn = {2041-1723}, mesh = {Animals ; Base Sequence ; *Biological Evolution ; Carcinogenesis/*pathology ; Comparative Genomic Hybridization ; Exome/genetics ; Heterografts/*physiopathology ; *Models, Biological ; Neoplasm Metastasis/*genetics/*physiopathology ; Neoplasms/genetics/*physiopathology ; Sequence Analysis, DNA ; }, abstract = {Theoretical reasoning suggests that cancer may result from a knockdown of the genetic constraints that evolved for the maintenance of metazoan multicellularity. By characterizing the whole-life history of a xenograft tumour, here we show that metastasis is driven by positive selection for general loss-of-function mutations on multicellularity-related genes. Expression analyses reveal mainly downregulation of multicellularity-related genes and an evolving expression profile towards that of embryonic stem cells, the cell type resembling unicellular life in its capacity of unlimited clonal proliferation. Also, the emergence of metazoan multicellularity ~600 Myr ago is accompanied by an elevated birth rate of cancer genes, and there are more loss-of-function tumour suppressors than activated oncogenes in a typical tumour. These data collectively suggest that cancer represents a loss-of-function-driven reverse evolution back to the unicellular 'ground state'. This cancer evolution model may account for inter-/intratumoural genetic heterogeneity, could explain distant-organ metastases and hold implications for cancer therapy.}, } @article {pmid25750178, year = {2015}, author = {Jin, J and He, K and Tang, X and Li, Z and Lv, L and Zhao, Y and Luo, J and Gao, G}, title = {An Arabidopsis Transcriptional Regulatory Map Reveals Distinct Functional and Evolutionary Features of Novel Transcription Factors.}, journal = {Molecular biology and evolution}, volume = {32}, number = {7}, pages = {1767-1773}, pmid = {25750178}, issn = {1537-1719}, mesh = {Arabidopsis/*genetics/physiology ; *Evolution, Molecular ; Gene Expression Regulation, Plant ; Gene Regulatory Networks/*genetics ; Protein Binding ; Stress, Physiological/genetics ; Transcription Factors/*metabolism ; }, abstract = {Transcription factors (TFs) play key roles in both development and stress responses. By integrating into and rewiring original systems, novel TFs contribute significantly to the evolution of transcriptional regulatory networks. Here, we report a high-confidence transcriptional regulatory map covering 388 TFs from 47 families in Arabidopsis. Systematic analysis of this map revealed the architectural heterogeneity of developmental and stress response subnetworks and identified three types of novel network motifs that are absent from unicellular organisms and essential for multicellular development. Moreover, TFs of novel families that emerged during plant landing present higher binding specificities and are preferentially wired into developmental processes and these novel network motifs. Further unveiled connection between the binding specificity and wiring preference of TFs explains the wiring preferences of novel-family TFs. These results reveal distinct functional and evolutionary features of novel TFs, suggesting a plausible mechanism for their contribution to the evolution of multicellular organisms.}, } @article {pmid25745427, year = {2015}, author = {Wichard, T and Charrier, B and Mineur, F and Bothwell, JH and Clerck, OD and Coates, JC}, title = {The green seaweed Ulva: a model system to study morphogenesis.}, journal = {Frontiers in plant science}, volume = {6}, number = {}, pages = {72}, pmid = {25745427}, issn = {1664-462X}, abstract = {Green macroalgae, mostly represented by the Ulvophyceae, the main multicellular branch of the Chlorophyceae, constitute important primary producers of marine and brackish coastal ecosystems. Ulva or sea lettuce species are some of the most abundant representatives, being ubiquitous in coastal benthic communities around the world. Nonetheless the genus also remains largely understudied. This review highlights Ulva as an exciting novel model organism for studies of algal growth, development and morphogenesis as well as mutualistic interactions. The key reasons that Ulva is potentially such a good model system are: (i) patterns of Ulva development can drive ecologically important events, such as the increasing number of green tides observed worldwide as a result of eutrophication of coastal waters, (ii) Ulva growth is symbiotic, with proper development requiring close association with bacterial epiphytes, (iii) Ulva is extremely developmentally plastic, which can shed light on the transition from simple to complex multicellularity and (iv) Ulva will provide additional information about the evolution of the green lineage.}, } @article {pmid25737280, year = {2015}, author = {Murn, J and Zarnack, K and Yang, YJ and Durak, O and Murphy, EA and Cheloufi, S and Gonzalez, DM and Teplova, M and Curk, T and Zuber, J and Patel, DJ and Ule, J and Luscombe, NM and Tsai, LH and Walsh, CA and Shi, Y}, title = {Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt.}, journal = {Genes & development}, volume = {29}, number = {5}, pages = {501-512}, pmid = {25737280}, issn = {1549-5477}, support = {R01 NS032457/NS/NINDS NIH HHS/United States ; R01 NS35129/NS/NINDS NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; R01 CA118487/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 HD018655/HD/NICHD NIH HHS/United States ; MH096066/MH/NIMH NIH HHS/United States ; R01 NS035129/NS/NINDS NIH HHS/United States ; R01 MH096066/MH/NIMH NIH HHS/United States ; CA118487/CA/NCI NIH HHS/United States ; R01 GM058012/GM/NIGMS NIH HHS/United States ; GM058012/GM/NIGMS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; T32GM007753/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Brain/metabolism ; Cell Line ; Cell Shape/*genetics ; Embryo, Mammalian ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; HeLa Cells ; Humans ; Mice ; Neurons/*cytology ; Protein Binding ; RNA, Messenger ; }, abstract = {Cellular morphology is an essential determinant of cellular function in all kingdoms of life, yet little is known about how cell shape is controlled. Here we describe a molecular program that controls the early morphology of neurons through a metazoan-specific zinc finger protein, Unkempt. Depletion of Unkempt in mouse embryos disrupts the shape of migrating neurons, while ectopic expression confers neuronal-like morphology to cells of different nonneuronal lineages. We found that Unkempt is a sequence-specific RNA-binding protein and identified its precise binding sites within coding regions of mRNAs linked to protein metabolism and trafficking. RNA binding is required for Unkempt-induced remodeling of cellular shape and is directly coupled to a reduced production of the encoded proteins. These findings link post-transcriptional regulation of gene expression with cellular shape and have general implications for the development and disease of multicellular organisms.}, } @article {pmid25736565, year = {2015}, author = {Neumann, S and El Maadidi, S and Faletti, L and Haun, F and Labib, S and Schejtman, A and Maurer, U and Borner, C}, title = {How do viruses control mitochondria-mediated apoptosis?.}, journal = {Virus research}, volume = {209}, number = {}, pages = {45-55}, pmid = {25736565}, issn = {1872-7492}, mesh = {*Apoptosis ; *Host-Pathogen Interactions ; Humans ; *Immunity, Innate ; Mitochondria/*metabolism ; *Virus Replication ; Viruses/*growth & development/*immunology ; }, abstract = {There is no doubt that viruses require cells to successfully reproduce and effectively infect the next host. The question is what is the fate of the infected cells? All eukaryotic cells can "sense" viral infections and exhibit defence strategies to oppose viral replication and spread. This often leads to the elimination of the infected cells by programmed cell death or apoptosis. This "sacrifice" of infected cells represents the most primordial response of multicellular organisms to viruses. Subverting host cell apoptosis, at least for some time, is therefore a crucial strategy of viruses to ensure their replication, the production of essential viral proteins, virus assembly and the spreading to new hosts. For that reason many viruses harbor apoptosis inhibitory genes, which once inside infected cells are expressed to circumvent apoptosis induction during the virus reproduction phase. On the other hand, viruses can take advantage of stimulating apoptosis to (i) facilitate shedding and hence dissemination, (ii) to prevent infected cells from presenting viral antigens to the immune system or (iii) to kill non-infected bystander and immune cells which would limit viral propagation. Hence the decision whether an infected host cell undergoes apoptosis or not depends on virus type and pathogenicity, its capacity to oppose antiviral responses of the infected cells and/or to evade any attack from immune cells. Viral genomes have therefore been adapted throughout evolution to satisfy the need of a particular virus to induce or inhibit apoptosis during its life cycle. Here we review the different strategies used by viruses to interfere with the two major apoptosis as well as with the innate immune signaling pathways in mammalian cells. We will focus on the intrinsic mitochondrial pathway and discuss new ideas about how particular viruses could activately engage mitochondria to induce apoptosis of their host.}, } @article {pmid25735194, year = {2015}, author = {Zhao, JL and Pan, JS and Guan, Y and Zhang, WW and Bie, BB and Wang, YL and He, HL and Lian, HL and Cai, R}, title = {Micro-trichome as a class I homeodomain-leucine zipper gene regulates multicellular trichome development in Cucumis sativus.}, journal = {Journal of integrative plant biology}, volume = {57}, number = {11}, pages = {925-935}, doi = {10.1111/jipb.12345}, pmid = {25735194}, issn = {1744-7909}, mesh = {Amino Acid Sequence ; Cucumis sativus/*genetics/growth & development/ultrastructure ; Homeodomain Proteins/*physiology ; Leucine Zippers ; Molecular Sequence Data ; Phenotype ; Phylogeny ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Transcriptome ; Trichomes/*growth & development/ultrastructure ; }, abstract = {Plant trichomes serve as a highly suitable model for investigating cell differentiation at the single-cell level. The regulatory genes involved in unicellular trichome development in Arabidopsis thaliana have been intensively studied, but genes regulating multicellular trichome development in plants remain unclear. Here, we characterized Cucumis sativus (cucumber) trichomes as representative multicellular and unbranched structures, and identified Micro-trichome (Mict), using map-based cloning in an F2 segregating population of 7,936 individuals generated from a spontaneous mict mutant. In mict plants, trichomes in both leaves and fruits, are small, poorly developed, and denser than in the wild type. Sequence analysis revealed that a 2,649-bp genomic deletion, spanning the first and second exons, occurred in a plant-specific class I homeodomain-leucine zipper gene. Tissue-specific expression analysis indicated that Mict is strongly expressed in the trichome cells. Transcriptome profiling identified potential targets of Mict including putative homologs of genes known in other systems to regulate trichome development, meristem determinacy, and hormone responsiveness. Phylogenic analysis charted the relationships among putative homologs in angiosperms. Our paper represents initial steps toward understanding the development of multicellular trichomes.}, } @article {pmid25734540, year = {2015}, author = {Hayakawa, S and Takaku, Y and Hwang, JS and Horiguchi, T and Suga, H and Gehring, W and Ikeo, K and Gojobori, T}, title = {Function and evolutionary origin of unicellular camera-type eye structure.}, journal = {PloS one}, volume = {10}, number = {3}, pages = {e0118415}, pmid = {25734540}, issn = {1932-6203}, mesh = {Animal Structures/*physiology/radiation effects/ultrastructure ; Animals ; Biological Evolution ; Dinoflagellida/classification/*physiology/radiation effects/ultrastructure ; Gene Expression ; In Situ Hybridization ; Lens, Crystalline/*physiology/radiation effects/ultrastructure ; Light ; Photic Stimulation ; Photoreceptor Cells/*physiology/radiation effects/ultrastructure ; Phylogeny ; Protozoan Proteins/genetics/*metabolism ; Rhodopsin/genetics/*metabolism ; Rhodopsins, Microbial/genetics/metabolism ; Sequence Homology, Amino Acid ; Symbiosis/physiology ; }, abstract = {The ocelloid is an extraordinary eyespot organelle found only in the dinoflagellate family Warnowiaceae. It contains retina- and lens-like structures called the retinal body and the hyalosome. The ocelloid has been an evolutionary enigma because of its remarkable resemblance to the multicellular camera-type eye. To determine if the ocelloid is functionally photoreceptive, we investigated the warnowiid dinoflagellate Erythropsidinium. Here, we show that the morphology of the retinal body changed depending on different illumination conditions and the hyalosome manifests the refractile nature. Identifying a rhodopsin gene fragment in Erythropsidinium ESTs that is expressed in the retinal body by in situ hybridization, we also show that ocelloids are actually light sensitive photoreceptors. The rhodopsin gene identified is most closely related to bacterial rhodopsins. Taken together, we suggest that the ocelloid is an intracellular camera-type eye, which might be originated from endosymbiotic origin.}, } @article {pmid25734073, year = {2015}, author = {Cullen, PJ}, title = {Investigating filamentous growth and biofilm/mat formation in budding yeast.}, journal = {Cold Spring Harbor protocols}, volume = {2015}, number = {3}, pages = {235-238}, pmid = {25734073}, issn = {1559-6095}, support = {R01 GM098629/GM/NIGMS NIH HHS/United States ; GM098629/GM/NIGMS NIH HHS/United States ; }, mesh = {Biofilms/*growth & development ; Hyphae/*growth & development ; Saccharomycetales/*cytology/growth & development/*physiology ; }, abstract = {In response to nutrient limitation, budding yeast can undergo filamentous growth by differentiating into elongated chains of interconnected cells. Filamentous growth is regulated by signal transduction pathways that oversee the reorganization of cell polarity, changes to the cell cycle, and an increase in cell adhesion that occur in response to nutrient limitation. Each of these changes can be easily measured. Yeast can also grow colonially atop surfaces in a biofilm or mat of connected cells. Filamentous growth and biofilm/mat formation require cooperation among individuals; therefore, studying these responses can shed light on the origin and genetic basis of multicellular behaviors. The assays introduced here can be used to study analogous behaviors in other fungal species, including pathogens, which require filamentous growth and biofilm/mat formation for virulence.}, } @article {pmid25733140, year = {2015}, author = {McCrea, PD and Maher, MT and Gottardi, CJ}, title = {Nuclear signaling from cadherin adhesion complexes.}, journal = {Current topics in developmental biology}, volume = {112}, number = {}, pages = {129-196}, pmid = {25733140}, issn = {1557-8933}, support = {R01 GM076561/GM/NIGMS NIH HHS/United States ; R01 GM107079/GM/NIGMS NIH HHS/United States ; GM076561/GM/NIGMS NIH HHS/United States ; GM107079/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cadherins/*metabolism ; Cell Adhesion/*physiology ; Cell Nucleus/*metabolism ; Humans ; Signal Transduction ; beta Catenin/*metabolism ; }, abstract = {The arrival of multicellularity in evolution facilitated cell-cell signaling in conjunction with adhesion. As the ectodomains of cadherins interact with each other directly in trans (as well as in cis), spanning the plasma membrane and associating with multiple other entities, cadherins enable the transduction of "outside-in" or "inside-out" signals. We focus this review on signals that originate from the larger family of cadherins that are inwardly directed to the nucleus, and thus have roles in gene control or nuclear structure-function. The nature of cadherin complexes varies considerably depending on the type of cadherin and its context, and we will address some of these variables for classical cadherins versus other family members. Substantial but still fragmentary progress has been made in understanding the signaling mediators used by varied cadherin complexes to coordinate the state of cell-cell adhesion with gene expression. Evidence that cadherin intracellular binding partners also localize to the nucleus is a major point of interest. In some models, catenins show reduced binding to cadherin cytoplasmic tails favoring their engagement in gene control. When bound, cadherins may serve as stoichiometric competitors of nuclear signals. Cadherins also directly or indirectly affect numerous signaling pathways (e.g., Wnt, receptor tyrosine kinase, Hippo, NFκB, and JAK/STAT), enabling cell-cell contacts to touch upon multiple biological outcomes in embryonic development and tissue homeostasis.}, } @article {pmid25710177, year = {2015}, author = {Erives, AJ and Fassler, JS}, title = {Metabolic and chaperone gene loss marks the origin of animals: evidence for Hsp104 and Hsp78 chaperones sharing mitochondrial enzymes as clients.}, journal = {PloS one}, volume = {10}, number = {2}, pages = {e0117192}, pmid = {25710177}, issn = {1932-6203}, mesh = {Aconitate Hydratase/classification/genetics ; Animals ; Bayes Theorem ; Choanoflagellata/genetics ; Endopeptidase Clp/classification/genetics ; Heat-Shock Proteins/*genetics/metabolism ; Likelihood Functions ; Mitochondria/*enzymology/metabolism ; Mutation ; Phylogeny ; Promoter Regions, Genetic ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; }, abstract = {The evolution of animals involved acquisition of an emergent gene repertoire for gastrulation. Whether loss of genes also co-evolved with this developmental reprogramming has not yet been addressed. Here, we identify twenty-four genetic functions that are retained in fungi and choanoflagellates but undetectable in animals. These lost genes encode: (i) sixteen distinct biosynthetic functions; (ii) the two ancestral eukaryotic ClpB disaggregases, Hsp78 and Hsp104, which function in the mitochondria and cytosol, respectively; and (iii) six other assorted functions. We present computational and experimental data that are consistent with a joint function for the differentially localized ClpB disaggregases, and with the possibility of a shared client/chaperone relationship between the mitochondrial Fe/S homoaconitase encoded by the lost LYS4 gene and the two ClpBs. Our analyses lead to the hypothesis that the evolution of gastrulation-based multicellularity in animals led to efficient extraction of nutrients from dietary sources, loss of natural selection for maintenance of energetically expensive biosynthetic pathways, and subsequent loss of their attendant ClpB chaperones.}, } @article {pmid25705370, year = {2014}, author = {Layden, MJ and Martindale, MQ}, title = {Non-canonical Notch signaling represents an ancestral mechanism to regulate neural differentiation.}, journal = {EvoDevo}, volume = {5}, number = {}, pages = {30}, pmid = {25705370}, issn = {2041-9139}, support = {R01 GM093116/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Cellular differentiation is a critical process during development of multicellular animals that must be tightly controlled in order to avoid precocious differentiation or failed generation of differentiated cell types. Research in flies, vertebrates, and nematodes has led to the identification of a conserved role for Notch signaling as a mechanism to regulate cellular differentiation regardless of tissue/cell type. Notch signaling can occur through a canonical pathway that results in the activation of hes gene expression by a complex consisting of the Notch intracellular domain, SuH, and the Mastermind co-activator. Alternatively, Notch signaling can occur via a non-canonical mechanism that does not require SuH or activation of hes gene expression. Regardless of which mechanism is being used, high Notch activity generally inhibits further differentiation, while low Notch activity promotes differentiation. Flies, vertebrates, and nematodes are all bilaterians, and it is therefore unclear if Notch regulation of differentiation is a bilaterian innovation, or if it represents a more ancient mechanism in animals.

RESULTS: To reconstruct the ancestral function of Notch signaling we investigate Notch function in a non-bilaterian animal, the sea anemone Nematostella vectensis (Cnidaria). Morpholino or pharmacological knockdown of Nvnotch causes increased expression of the neural differentiation gene NvashA. Conversely, overactivation of Notch activity resulting from overexpression of the Nvnotch intracellular domain or by overexpression of the Notch ligand Nvdelta suppresses NvashA. We also knocked down or overactivated components of the canonical Notch signaling pathway. We disrupted NvsuH with morpholino or by overexpressing a dominant negative NvsuH construct. We saw no change in expression levels for Nvhes genes or NvashA. Overexpression of Nvhes genes did not alter NvashA expression levels. Lastly, we tested additional markers associated with neuronal differentiation and observed that non-canonical Notch signaling broadly suppresses neural differentiation in Nematostella.

CONCLUSIONS: We conclude that one ancestral role for Notch in metazoans was to regulate neural differentiation. Remarkably, we found no evidence for a functional canonical Notch pathway during Nematostella embryogenesis, suggesting that the non-canonical hes-independent Notch signaling mechanism may represent an ancestral Notch signaling pathway.}, } @article {pmid25696824, year = {2015}, author = {Satterlie, RA}, title = {The search for ancestral nervous systems: an integrative and comparative approach.}, journal = {The Journal of experimental biology}, volume = {218}, number = {Pt 4}, pages = {612-617}, doi = {10.1242/jeb.110387}, pmid = {25696824}, issn = {1477-9145}, mesh = {Animals ; Behavior, Animal ; Biological Evolution ; Cnidaria/anatomy & histology/*physiology ; Ctenophora/anatomy & histology/*physiology ; *Nervous System Physiological Phenomena ; Phylogeny ; }, abstract = {Even the most basal multicellular nervous systems are capable of producing complex behavioral acts that involve the integration and combination of simple responses, and decision-making when presented with conflicting stimuli. This requires an understanding beyond that available from genomic investigations, and calls for a integrative and comparative approach, where the power of genomic/transcriptomic techniques is coupled with morphological, physiological and developmental experimentation to identify common and species-specific nervous system properties for the development and elaboration of phylogenomic reconstructions. With careful selection of genes and gene products, we can continue to make significant progress in our search for ancestral nervous system organizations.}, } @article {pmid25688864, year = {2015}, author = {Mendes, TK and Novakovic, S and Raymant, G and Bertram, SE and Esmaillie, R and Nadarajan, S and Breugelmans, B and Hofmann, A and Gasser, RB and Colaiácovo, MP and Boag, PR}, title = {Investigating the role of RIO protein kinases in Caenorhabditis elegans.}, journal = {PloS one}, volume = {10}, number = {2}, pages = {e0117444}, pmid = {25688864}, issn = {1932-6203}, support = {R01 GM072551/GM/NIGMS NIH HHS/United States ; R01 GM105853/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Animals, Genetically Modified/metabolism ; Caenorhabditis elegans/*enzymology/genetics ; Caenorhabditis elegans Proteins/antagonists & inhibitors/classification/*metabolism ; Cell Proliferation ; Female ; Genome ; Germ Cells/cytology/metabolism ; Gonads/metabolism ; Male ; Phylogeny ; Promoter Regions, Genetic ; Protein Kinases/classification/genetics/*metabolism ; RNA Interference ; RNA, Double-Stranded/metabolism ; Sequence Alignment ; }, abstract = {RIO protein kinases (RIOKs) are a relatively conserved family of enzymes implicated in cell cycle control and ribosomal RNA processing. Despite their functional importance, they remain a poorly understood group of kinases in multicellular organisms. Here, we show that the C. elegans genome contains one member of each of the three RIOK sub-families and that each of the genes coding for them has a unique tissue expression pattern. Our analysis showed that the gene encoding RIOK-1 (riok-1) was broadly and strongly expressed. Interestingly, the intestinal expression of riok-1 was dependent upon two putative binding sites for the oxidative and xenobiotic stress response transcription factor SKN-1. RNA interference (RNAi)-mediated knock down of riok-1 resulted in germline defects, including defects in germ line stem cell proliferation, oocyte maturation and the production of endomitotic oocytes. Taken together, our findings indicate new functions for RIOK-1 in post mitotic tissues and in reproduction.}, } @article {pmid25688421, year = {2015}, author = {Bastiaans, E and Debets, AJ and Aanen, DK}, title = {Experimental demonstration of the benefits of somatic fusion and the consequences for allorecognition.}, journal = {Evolution; international journal of organic evolution}, volume = {69}, number = {4}, pages = {1091-1099}, doi = {10.1111/evo.12626}, pmid = {25688421}, issn = {1558-5646}, mesh = {Alleles ; *Biological Evolution ; Genetic Fitness ; *Genetic Variation ; Neurospora crassa/cytology/*genetics ; Spores, Fungal/cytology ; }, abstract = {Allorecognition, the ability to distinguish "self" from "nonself" based on allelic differences at allorecognition loci, is common in all domains of life. Allorecognition restricts the opportunities for social parasitism, and is therefore crucial for the evolution of cooperation. However, the maintenance of allorecognition diversity provides a paradox. If allorecognition is costly relative to cooperation, common alleles will be favored. Thus, the cost of allorecognition may reduce the genetic variation upon which allorecognition crucially relies, a prediction now known as "Crozier's paradox." We establish the relative costs of allorecognition, and their consequences for the short-term evolution of recognition labels theoretically predicted by Crozier. We use fusion among colonies of the fungus Neurospora crassa, regulated by highly variable allorecognition genes, as an experimental model system. We demonstrate that fusion among colonies is mutually beneficial, relative to absence of fusion upon allorecognition. This benefit is due not only to absence of mutual antagonism, which occurs upon allorecognition, but also to an increase in colony size per se. We then experimentally demonstrate that the benefit of fusion selects against allorecognition diversity, as predicted by Crozier. We discuss what maintains allorecognition diversity.}, } @article {pmid25685543, year = {2015}, author = {Abdallah, HM and Al-Abd, AM and El-Dine, RS and El-Halawany, AM}, title = {P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review.}, journal = {Journal of advanced research}, volume = {6}, number = {1}, pages = {45-62}, pmid = {25685543}, issn = {2090-1232}, abstract = {Resistance of solid tumors to treatment is significantly attributed to pharmacokinetic reasons at both cellular and multi-cellular levels. Anticancer agent must be bio-available at the site of action in a cytotoxic concentration to exert its proposed activity. P-glycoprotein (P-gp) is a member of the ATP-dependent membrane transport proteins; it is known to pump substrates out of cells in ATP-dependent mechanism. The over-expression of P-gp in tumor cells reduces the intracellular drug concentrations, which decreases the cytotoxicity of a broad spectrum of antitumor drugs. Accordingly, P-gp inhibitors/blockers are potential enhancer for the cellular bioavailability of several clinically important anticancer drugs such as, anthracyclines, taxanes, vinca alkaloids, and podophyllotoxins. Besides several chemically synthesized P-gp inhibitors/blockers, some naturally occurring compounds and plant extracts were reported for their modulation of multidrug resistance; however, this review will focus only on major classes of naturally occurring inhibitors viz., flavonoids, coumarins, terpenoids, alkaloids and saponins.}, } @article {pmid25678667, year = {2015}, author = {Worden, AZ and Follows, MJ and Giovannoni, SJ and Wilken, S and Zimmerman, AE and Keeling, PJ}, title = {Environmental science. Rethinking the marine carbon cycle: factoring in the multifarious lifestyles of microbes.}, journal = {Science (New York, N.Y.)}, volume = {347}, number = {6223}, pages = {1257594}, doi = {10.1126/science.1257594}, pmid = {25678667}, issn = {1095-9203}, mesh = {Animals ; Biological Evolution ; *Carbon Cycle ; Eukaryota/*metabolism ; Phytoplankton/*metabolism ; Seawater/*microbiology ; Symbiosis ; Zooplankton/*metabolism ; }, abstract = {The profound influence of marine plankton on the global carbon cycle has been recognized for decades, particularly for photosynthetic microbes that form the base of ocean food chains. However, a comprehensive model of the carbon cycle is challenged by unicellular eukaryotes (protists) having evolved complex behavioral strategies and organismal interactions that extend far beyond photosynthetic lifestyles. As is also true for multicellular eukaryotes, these strategies and their associated physiological changes are difficult to deduce from genome sequences or gene repertoires—a problem compounded by numerous unknown function proteins. Here, we explore protistan trophic modes in marine food webs and broader biogeochemical influences. We also evaluate approaches that could resolve their activities, link them to biotic and abiotic factors, and integrate them into an ecosystems biology framework.}, } @article {pmid25675537, year = {2015}, author = {Liebeskind, BJ and Hillis, DM and Zakon, HH}, title = {Convergence of ion channel genome content in early animal evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {8}, pages = {E846-51}, pmid = {25675537}, issn = {1091-6490}, support = {R01 DK051131/DK/NIDDK NIH HHS/United States ; R01 DK069463/DK/NIDDK NIH HHS/United States ; R01 GM095538/GM/NIGMS NIH HHS/United States ; //Intramural NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Extinction, Biological ; Genome/*genetics ; Ion Channels/*genetics ; Multigene Family ; Nervous System/metabolism ; Phylogeny ; }, abstract = {Multicellularity has evolved multiple times, but animals are the only multicellular lineage with nervous systems. This fact implies that the origin of nervous systems was an unlikely event, yet recent comparisons among extant taxa suggest that animal nervous systems may have evolved multiple times independently. Here, we use ancestral gene content reconstruction to track the timing of gene family expansions for the major families of ion-channel proteins that drive nervous system function. We find that animals with nervous systems have broadly similar complements of ion-channel types but that these complements likely evolved independently. We also find that ion-channel gene family evolution has included large loss events, two of which were immediately followed by rounds of duplication. Ctenophores, cnidarians, and bilaterians underwent independent bouts of gene expansion in channel families involved in synaptic transmission and action potential shaping. We suggest that expansions of these family types may represent a genomic signature of expanding nervous system complexity. Ancestral nodes in which nervous systems are currently hypothesized to have originated did not experience large expansions, making it difficult to distinguish among competing hypotheses of nervous system origins and suggesting that the origin of nerves was not attended by an immediate burst of complexity. Rather, the evolution of nervous system complexity appears to resemble a slow fuse in stem animals followed by many independent bouts of gene gain and loss.}, } @article {pmid25674102, year = {2015}, author = {Palazzo, AF and Lee, ES}, title = {Non-coding RNA: what is functional and what is junk?.}, journal = {Frontiers in genetics}, volume = {6}, number = {}, pages = {2}, pmid = {25674102}, issn = {1664-8021}, abstract = {The genomes of large multicellular eukaryotes are mostly comprised of non-protein coding DNA. Although there has been much agreement that a small fraction of these genomes has important biological functions, there has been much debate as to whether the rest contributes to development and/or homeostasis. Much of the speculation has centered on the genomic regions that are transcribed into RNA at some low level. Unfortunately these RNAs have been arbitrarily assigned various names, such as "intergenic RNA," "long non-coding RNAs" etc., which have led to some confusion in the field. Many researchers believe that these transcripts represent a vast, unchartered world of functional non-coding RNAs (ncRNAs), simply because they exist. However, there are reasons to question this Panglossian view because it ignores our current understanding of how evolution shapes eukaryotic genomes and how the gene expression machinery works in eukaryotic cells. Although there are undoubtedly many more functional ncRNAs yet to be discovered and characterized, it is also likely that many of these transcripts are simply junk. Here, we discuss how to determine whether any given ncRNA has a function. Importantly, we advocate that in the absence of any such data, the appropriate null hypothesis is that the RNA in question is junk.}, } @article {pmid25667072, year = {2015}, author = {Takahashi, N and Kami, C and Ota, I and Morita, N and Imaichi, R}, title = {Developmental morphology of the typical cordate gametophyte of a homosporous leptosporangiate fern, Lygodium japonicum (Lygodiaceae), focusing on the initial cell behavior of two distinct meristems.}, journal = {American journal of botany}, volume = {102}, number = {2}, pages = {197-207}, doi = {10.3732/ajb.1400333}, pmid = {25667072}, issn = {1537-2197}, mesh = {Biological Evolution ; Cell Division ; Ferns/anatomy & histology/*growth & development ; Germ Cells, Plant/*growth & development ; Meristem/*growth & development ; *Plant Cells ; Polypodiaceae ; Spores ; }, abstract = {PREMISE OF THE STUDY: Understanding the origin and early evolution of vascular plants requires thorough consideration of the gametophyte generation of ferns and lycophytes. Unfortunately, information about this generation is quite limited. To reveal the origin and evolution of varied gametophyte shapes, we used comparative morphological studies of meristem behavior of gametophytes of Lygodium japonicum, which exhibit the typical cordate shape.

METHODS: Microscopic images of epi-illuminated growing gametophytes cultured from spores were captured periodically using a metallurgical microscope equipped with a digital camera to analyze the cell lineage in the meristem.

KEY RESULTS: Gametophytes form from two meristems: the apical-cell-based meristem and the multicellular meristem. The triangular apical cell produces six to eight derivatives from two lateral facets, then disappears. Subsequently, the multicellular meristem, with a row of several rectangular cells, forms in the notch. These rectangular cells divide asynchronously in the periclinal and anticlinal walls to produce cells to both lateral sides and downward. Usually two, and sometimes three, cells located at the center of the meristem divide at a slower pace in the periclinal and anticlinal planes than others at the periphery. The cells at the periphery are pushed away and become involved in the wing base.

CONCLUSIONS: The triangular apical cell behaves as a permanent initial cell. In the multicellular meristem, however, two or three central cells behave as initial cells that are transient and regulated in a position-dependent manner. The organization and behavior of both meristems are shared with the ribbon-shaped gametophytes of Colysis.}, } @article {pmid25662101, year = {2015}, author = {He, Y and Cao, X and Li, K and Hu, Y and Chen, YR and Blissard, G and Kanost, MR and Jiang, H}, title = {A genome-wide analysis of antimicrobial effector genes and their transcription patterns in Manduca sexta.}, journal = {Insect biochemistry and molecular biology}, volume = {62}, number = {}, pages = {23-37}, pmid = {25662101}, issn = {1879-0240}, support = {R37 GM041247/GM/NIGMS NIH HHS/United States ; GM58634/GM/NIGMS NIH HHS/United States ; GM041247/GM/NIGMS NIH HHS/United States ; R01 GM058634/GM/NIGMS NIH HHS/United States ; R01 GM041247/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antimicrobial Cationic Peptides/chemistry/*genetics/immunology ; Gene Expression Profiling ; *Genome, Insect ; Immunity, Innate/genetics ; Insect Proteins/chemistry/*genetics/immunology ; Larva/genetics/immunology ; Manduca/*genetics/immunology/metabolism ; Molecular Sequence Data ; Phylogeny ; Protein Conformation ; *Transcriptome ; }, abstract = {Antimicrobial proteins/peptides (AMPs) are effectors of innate immune systems against pathogen infection in multicellular organisms. Over half of the AMPs reported so far come from insects, and these effectors act in concert to suppress or kill bacteria, fungi, viruses, and parasites. In this work, we have identified 86 AMP genes in the Manduca sexta genome, most of which seem likely to be functional. They encode 15 cecropins, 6 moricins, 6 defensins, 3 gallerimycins, 4 X-tox splicing variants, 14 diapausins, 15 whey acidic protein homologs, 11 attacins, 1 gloverin, 4 lebocins, 6 lysozyme-related proteins, and 4 transferrins. Some of these genes (e.g. attacins, cecropins) constitute large clusters, likely arising after rounds of gene duplication. We compared the amino acid sequences of M. sexta AMPs with their homologs in other insects to reveal conserved structural features and phylogenetic relationships. Expression data showed that many of them are synthesized in fat body and midgut during the larval-pupal molt. Certain genes contain one or more predicted κB binding sites and other regulatory elements in their promoter regions, which may account for the dramatic mRNA level increases in fat body and hemocytes after an immune challenge. Consistent with these strong mRNA increases, many AMPs become highly abundant in the larval plasma at 24 h after the challenge, as demonstrated in our previous peptidomic study. Taken together, these data suggest the existence of a large repertoire of AMPs in M. sexta, whose expression is up-regulated via immune signaling pathways to fight off invading pathogens in a coordinated manner.}, } @article {pmid25659377, year = {2015}, author = {Godin, SK and Meslin, C and Kabbinavar, F and Bratton-Palmer, DS and Hornack, C and Mihalevic, MJ and Yoshida, K and Sullivan, M and Clark, NL and Bernstein, KA}, title = {Evolutionary and functional analysis of the invariant SWIM domain in the conserved Shu2/SWS1 protein family from Saccharomyces cerevisiae to Homo sapiens.}, journal = {Genetics}, volume = {199}, number = {4}, pages = {1023-1033}, pmid = {25659377}, issn = {1943-2631}, support = {R01 ES024872/ES/NIEHS NIH HHS/United States ; ES-0244872/ES/NIEHS NIH HHS/United States ; K99 GM088413/GM/NIGMS NIH HHS/United States ; GM-088413/GM/NIGMS NIH HHS/United States ; R00 GM088413/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Cell Cycle Proteins/*genetics/metabolism ; *Conserved Sequence ; *Evolution, Molecular ; Humans ; Molecular Sequence Data ; Multigene Family ; Protein Structure, Tertiary ; Saccharomyces cerevisiae/*genetics ; Schizosaccharomyces pombe Proteins/*genetics/metabolism ; }, abstract = {The Saccharomyces cerevisiae Shu2 protein is an important regulator of Rad51, which promotes homologous recombination (HR). Shu2 functions in the Shu complex with Shu1 and the Rad51 paralogs Csm2 and Psy3. Shu2 belongs to the SWS1 protein family, which is characterized by its SWIM domain (CXC...Xn...CXH), a zinc-binding motif. In humans, SWS1 interacts with the Rad51 paralog SWSAP1. Using genetic and evolutionary analyses, we examined the role of the Shu complex in mitotic and meiotic processes across eukaryotic lineages. We provide evidence that the SWS1 protein family contains orthologous genes in early-branching eukaryote lineages (e.g., Giardia lamblia), as well as in multicellular eukaryotes including Caenorhabditis elegans and Drosophila melanogaster. Using sequence analysis, we expanded the SWIM domain to include an invariant alanine three residues after the terminal CXH motif (CXC…Xn…CXHXXA). We found that the SWIM domain is conserved in all eukaryotic orthologs, and accordingly, in vivo disruption of the invariant residues within the canonical SWIM domain inhibits DNA damage tolerance in yeast and protein-protein interactions in yeast and humans. Furthermore, using evolutionary analyses, we found that yeast and Drosophila Shu2 exhibit strong coevolutionary signatures with meiotic proteins, and in yeast, its disruption leads to decreased meiotic progeny. Together our data indicate that the SWS1 family is an ancient and highly conserved eukaryotic regulator of meiotic and mitotic HR.}, } @article {pmid25653025, year = {2015}, author = {Kuijper, B and Lane, N and Pomiankowski, A}, title = {Can paternal leakage maintain sexually antagonistic polymorphism in the cytoplasm?.}, journal = {Journal of evolutionary biology}, volume = {28}, number = {2}, pages = {468-480}, pmid = {25653025}, issn = {1420-9101}, mesh = {Alleles ; Animals ; Cytoplasm ; DNA, Mitochondrial/genetics ; Epistasis, Genetic ; Female ; Haploidy ; Male ; *Models, Genetic ; Polymorphism, Genetic/*genetics/physiology ; }, abstract = {A growing number of studies in multicellular organisms highlight low or moderate frequencies of paternal transmission of cytoplasmic organelles, including both mitochondria and chloroplasts. It is well established that strict maternal inheritance is selectively blind to cytoplasmic elements that are deleterious to males - 'mother's curse'. But it is not known how sensitive this conclusion is to slight levels of paternal cytoplasmic leakage. We assess the scope for polymorphism when individuals bear multiple cytoplasmic alleles in the presence of paternal leakage, bottlenecks and recurrent mutation. When fitness interactions among cytoplasmic elements within an individual are additive, we find that sexually antagonistic polymorphism is restricted to cases of strong selection on males. However, when fitness interactions among cytoplasmic elements are nonlinear, much more extensive polymorphism can be supported in the cytoplasm. In particular, mitochondrial mutants that have strong beneficial fitness effects in males and weak deleterious fitness effects in females when rare (i.e. 'reverse dominance') are strongly favoured under paternal leakage. We discuss how such epistasis could arise through preferential segregation of mitochondria in sex-specific somatic tissues. Our analysis shows how paternal leakage can dampen the evolution of deleterious male effects associated with predominant maternal inheritance of cytoplasm, potentially explaining why 'mother's curse' is less pervasive than predicted by earlier work.}, } @article {pmid25634491, year = {2015}, author = {Imamura, Y and Mukohara, T and Shimono, Y and Funakoshi, Y and Chayahara, N and Toyoda, M and Kiyota, N and Takao, S and Kono, S and Nakatsura, T and Minami, H}, title = {Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer.}, journal = {Oncology reports}, volume = {33}, number = {4}, pages = {1837-1843}, doi = {10.3892/or.2015.3767}, pmid = {25634491}, issn = {1791-2431}, mesh = {Antineoplastic Agents/pharmacology ; Breast Neoplasms/*drug therapy/metabolism ; Caspases/metabolism ; Cell Culture Techniques/*methods ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Female ; Humans ; Ki-67 Antigen/metabolism ; Spheroids, Cellular ; }, abstract = {It is becoming recognized that screening of oncology drugs on a platform using two-dimensionally (2D)-cultured cell lines is unable to precisely select clinically active drugs; therefore three-dimensional (3D)-culture systems are emerging and show potential for better simulating the in vivo tumor microenvironment. The purpose of this study was to reveal the differential effects of chemotherapeutic drugs between 2D- and 3D-cultures and to explore their underlying mechanisms. We evaluated differences between 2D- and 3D-cultured breast cancer cell lines by assessing drug sensitivity, oxygen status and expression of Ki-67 and caspases. Three cell lines (BT-549, BT-474 and T-47D) developed dense multicellular spheroids (MCSs) in 3D-culture, and showed greater resistance to paclitaxel and doxorubicin compared to the 2D-cultured cells. An additional three cell lines (MCF-7, HCC-1954, and MDA-MB‑231) developed only loose MCSs in 3D, and showed drug sensitivities similar to those found in the 2D-culture. Treatment with paclitaxel resulted in greater increases in cleaved-PARP expression in the 2D-culture compared with the 3D-culture, but only in cell lines forming dense 3D-MCSs, suggesting that MCS formation protected the cells from paclitaxel-induced apoptosis. Hypoxia was observed only in the dense 3D-MCSs. BT-549 had fewer cells positive for Ki-67 in 3D- than in 2D-culture, suggesting that the greater G0-dormant subpopulation was responsible for its drug resistance in the 3D-culture. BT-474 had a lower level of caspase-3 in the 3D- than in the 2D-culture, suggesting that the 3D-environment was anti-apoptotic. Finally, we compared staining for Ki-67 and caspases in the 2D- and 3D-primary‑cultured cells originating from a patient-derived xenograft (PDX), fresh PDX tumor, and the patient's original tumor; 2D-cultured cells showed greater proportions of Ki-67-positive and caspase-3-positive cells, in agreement with the view that 3D-primary culture better represents characteristics of tumors in vivo. In conclusion, 3D-cultured cells forming dense MCSs may be better than 2D-cultured cells in simulating important tumor characteristics in vivo, namely hypoxia, dormancy, anti-apoptotic features and their resulting drug resistance.}, } @article {pmid25634368, year = {2015}, author = {Cowie, P and Hay, EA and MacKenzie, A}, title = {The noncoding human genome and the future of personalised medicine.}, journal = {Expert reviews in molecular medicine}, volume = {17}, number = {}, pages = {e4}, doi = {10.1017/erm.2014.23}, pmid = {25634368}, issn = {1462-3994}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; //Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Genetic Predisposition to Disease ; Genome, Human/*genetics ; Humans ; *Precision Medicine ; Regulatory Sequences, Nucleic Acid/*genetics ; }, abstract = {Non-coding cis-regulatory sequences act as the 'eyes' of the genome and their role is to perceive, organise and relay cellular communication information to RNA polymerase II at gene promoters. The evolution of these sequences, that include enhancers, silencers, insulators and promoters, has progressed in multicellular organisms to the extent that cis-regulatory sequences make up as much as 10% of the human genome. Parallel evidence suggests that 75% of polymorphisms associated with heritable disease occur within predicted cis-regulatory sequences that effectively alter the 'perception' of cis-regulatory sequences or render them blind to cell communication cues. Cis-regulatory sequences also act as major functional targets of epigenetic modification thus representing an important conduit through which changes in DNA-methylation affects disease susceptibility. The objectives of the current review are (1) to describe what has been learned about identifying and characterising cis-regulatory sequences since the sequencing of the human genome; (2) to discuss their role in interpreting cell signalling pathways pathways; and (3) outline how this role may be altered by polymorphisms and epigenetic changes. We argue that the importance of the cis-regulatory genome for the interpretation of cellular communication pathways cannot be overstated and understanding its role in health and disease will be critical for the future development of personalised medicine.}, } @article {pmid25621522, year = {2015}, author = {Foox, J and Siddall, ME}, title = {The Road To Cnidaria: History of Phylogeny of the Myxozoa.}, journal = {The Journal of parasitology}, volume = {101}, number = {3}, pages = {269-274}, doi = {10.1645/14-671.1}, pmid = {25621522}, issn = {1937-2345}, mesh = {Animals ; Cnidaria/*classification/genetics ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Myxozoa/classification/genetics ; Parasitic Diseases/*history/*parasitology ; *Phylogeny ; }, abstract = {Myxozoans are a clade of highly derived cnidarians. The phylogenetic identity of these extremely simplified parasites of aquatic vertebrates and invertebrates had long been uncertain, with all early classifications designating Myxozoa as protists. Though suggestions were frequently made that the infective spores of these parasites are multicellular and possibly of cnidarian origin, it would take a phylogenetic analysis of ultrastructural developmental characters in combination with rRNA gene sequences to verify the Myxozoa as secondarily reduced cnidarians, sister to the polypoidozoan parasite Polypodium hydriforme . While a series of subsequent molecular studies suggested hypotheses of Myxozoa as basal bilaterians, triploblasts, or even nematodes, phylogenomic analyses with improved taxon sampling corroborated the landmark paper that verified the cnidarian nature of this group. This review of the body of phylogenetic work on Myxozoa aims to clarify historical progress and current knowledge, as well as to emphasize the opportune position that myxozoan biologists now are in, to address fundamental questions of cell biology of these parasites as well as the evolution of animal life.}, } @article {pmid25616141, year = {2015}, author = {Gilbert, OM}, title = {Histocompatibility as adaptive response to discriminatory within-organism conflict: a historical model.}, journal = {The American naturalist}, volume = {185}, number = {2}, pages = {228-242}, doi = {10.1086/679442}, pmid = {25616141}, issn = {1537-5323}, mesh = {Animals ; *Biological Evolution ; *Game Theory ; Histocompatibility/*genetics ; Invertebrates/genetics/*immunology ; *Models, Genetic ; }, abstract = {Multicellular tissue compatibility, or histocompatibility, restricts fusion to close kin. Histocompatibility depends on hypervariable cue genes, which often have more than 100 alleles in a population. To explain the evolution of histocompatibility, I here take a historical approach. I focus on the specific example of marine invertebrate histocompatibility. I use simple game-theoretical models to show that histocompatibility can evolve through five steps. These steps include the evolution of indiscriminate fusion, the evolution of discriminatory within-organism conflict, the evolution of minor histocompatibility, the evolution of major histocompatibility, and the evolution of major histocompatibility cue polymorphism. Allowing for gradual evolution reveals discriminatory within-organism conflict as a selective pressure for histocompatibility and associated cue polymorphism. Existing data from marine invertebrates and other organisms are consistent with this hypothesis.}, } @article {pmid25603395, year = {2015}, author = {Annenkova, NV and Hansen, G and Moestrup, Ø and Rengefors, K}, title = {Recent radiation in a marine and freshwater dinoflagellate species flock.}, journal = {The ISME journal}, volume = {9}, number = {8}, pages = {1821-1834}, pmid = {25603395}, issn = {1751-7370}, mesh = {DNA, Protozoan/analysis ; DNA, Ribosomal/genetics ; Dinoflagellida/genetics/*isolation & purification ; Lakes/*parasitology ; Phylogeny ; Russia ; Seawater/*parasitology ; Species Specificity ; }, abstract = {Processes of rapid radiation among unicellular eukaryotes are much less studied than among multicellular organisms. We have investigated a lineage of cold-water microeukaryotes (protists) that appear to have diverged recently. This lineage stands in stark contrast to known examples of phylogenetically closely related protists, in which genetic difference is typically larger than morphological differences. We found that the group not only consists of the marine-brackish dinoflagellate species Scrippsiella hangoei and the freshwater species Peridinium aciculiferum as discovered previously but also of a whole species flock. The additional species include Peridinium euryceps and Peridinium baicalense, which are restricted to a few lakes, in particular to the ancient Lake Baikal, Russia, and freshwater S. hangoei from Lake Baikal. These species are characterized by relatively large conspicuous morphological differences, which have given rise to the different species descriptions. However, our scanning electron microscopic studies indicate that they belong to a single genus according to traditional morphological characterization of dinoflagellates (thecal plate patterns). Moreover, we found that they have identical SSU (small subunit) rDNA fragments and distinct but very small differences in the DNA markers LSU (large subunit) rDNA, ITS2 (internal transcribed spacer 2) and COB (cytochrome b) gene, which are used to delineate dinoflagellates species. As some of the species co-occur, and all four have small but species-specific sequence differences, we suggest that these taxa are not a case of phenotypic plasticity but originated via recent adaptive radiation. We propose that this is the first clear example among free-living microeukaryotes of recent rapid diversification into several species followed by dispersion to environments with different ecological conditions.}, } @article {pmid25600558, year = {2015}, author = {Ratcliff, WC and Fankhauser, JD and Rogers, DW and Greig, D and Travisano, M}, title = {Origins of multicellular evolvability in snowflake yeast.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {6102}, pmid = {25600558}, issn = {2041-1723}, mesh = {Angiotensin-Converting Enzyme 2 ; Mutation ; Peptidyl-Dipeptidase A/genetics ; Saccharomyces cerevisiae/*cytology/*genetics/physiology ; }, abstract = {Complex life has arisen through a series of 'major transitions' in which collectives of formerly autonomous individuals evolve into a single, integrated organism. A key step in this process is the origin of higher-level evolvability, but little is known about how higher-level entities originate and gain the capacity to evolve as an individual. Here we report a single mutation that not only creates a new level of biological organization, but also potentiates higher-level evolvability. Disrupting the transcription factor ACE2 in Saccharomyces cerevisiae prevents mother-daughter cell separation, generating multicellular 'snowflake' yeast. Snowflake yeast develop through deterministic rules that produce geometrically defined clusters that preclude genetic conflict and display a high broad-sense heritability for multicellular traits; as a result they are preadapted to multicellular adaptation. This work demonstrates that simple microevolutionary changes can have profound macroevolutionary consequences, and suggests that the formation of clonally developing clusters may often be the first step to multicellularity.}, } @article {pmid25597443, year = {2015}, author = {Lyons, NA and Kolter, R}, title = {On the evolution of bacterial multicellularity.}, journal = {Current opinion in microbiology}, volume = {24}, number = {}, pages = {21-28}, pmid = {25597443}, issn = {1879-0364}, support = {R01 GM058213/GM/NIGMS NIH HHS/United States ; GM58218/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/cytology/*genetics/*growth & development ; Bacterial Physiological Phenomena ; Biological Evolution ; }, abstract = {Multicellularity is one of the most prevalent evolutionary innovations and nowhere is this more apparent than in the bacterial world, which contains many examples of multicellular organisms in a surprising array of forms. Due to their experimental accessibility and the large and diverse genomic data available, bacteria enable us to probe fundamental aspects of the origins of multicellularity. Here we discuss examples of multicellular behaviors in bacteria, the selective pressures that may have led to their evolution, possible origins and intermediate stages, and whether the ubiquity of apparently convergent multicellular forms argues for its inevitability.}, } @article {pmid25574294, year = {2014}, author = {Weber, CF}, title = {Hormones and antibiotics in nature: a laboratory module designed to broaden undergraduate perspectives on typically human-centered topics.}, journal = {Journal of microbiology & biology education}, volume = {15}, number = {2}, pages = {277-286}, pmid = {25574294}, issn = {1935-7877}, abstract = {Bringing discovery-based research into undergraduate laboratory courses increases student motivation and learning gains over traditional exercises that merely teach technique or demonstrate well-documented phenomena. Laboratory experiences are further enhanced when they are designed to challenge student perspectives on topics relevant to their lives. To this end, a laboratory module on antibiotics and hormones, which are generally discussed in the context of human health, was developed for students to explore the multifaceted roles of antibiotics and hormones in nature (e.g. interspecies communication) via reading primary scientific literature and performing discovery-based experiments. The main objective of this module was to increase the general biological literacy of students as determined by their ability to connect the Five Core Concepts of Biological Literacy (American Association for the Advancement of Science, Vision and Change in Undergraduate Education: A Call to Action, 2011) to the topics "hormones" and "antibiotics" in pre- and postmodule surveys. After discussing unpublished research findings, cell biology students performed experiments demonstrating that: 1) fungi may promote fern growth via hormone production, 2) novel bacterial isolates in the genus Streptomyces produce antifungal compounds, and 3) subinhibitory antibiotic concentrations may enhance soil bacterial growth. The third finding provided evidence supporting a hypothesis framed in a scientific article that students read and discussed. Student perspectives on premodule surveys focused on roles of hormones and antibiotics in the human body (e.g. development, fighting infection), but their broadened postmodule perspectives encompassed the roles of these molecules in organismal communication and possibly the evolution of multicellularity.}, } @article {pmid25573960, year = {2015}, author = {Boon, E and Halary, S and Bapteste, E and Hijri, M}, title = {Studying genome heterogeneity within the arbuscular mycorrhizal fungal cytoplasm.}, journal = {Genome biology and evolution}, volume = {7}, number = {2}, pages = {505-521}, pmid = {25573960}, issn = {1759-6653}, mesh = {Alleles ; Base Sequence ; Cluster Analysis ; Computer Simulation ; Cytoplasm/*genetics ; Evolution, Molecular ; Gene Dosage ; Genetic Markers ; *Genetic Variation ; Genome Size ; Genome, Fungal ; Glomeromycota/*genetics/isolation & purification ; Molecular Sequence Annotation ; Mutation/genetics ; Mycorrhizae/*genetics/isolation & purification ; Polymorphism, Genetic ; Real-Time Polymerase Chain Reaction ; Repetitive Sequences, Nucleic Acid/genetics ; Reproducibility of Results ; }, abstract = {Although heterokaryons have been reported in nature, multicellular organisms are generally assumed genetically homogeneous. Here, we investigate the case of arbuscular mycorrhizal fungi (AMF) that form symbiosis with plant roots. The growth advantages they confer to their hosts are of great potential benefit to sustainable agricultural practices. However, measuring genetic diversity for these coenocytes is a major challenge: Within the same cytoplasm, AMF contain thousands of nuclei and show extremely high levels of genetic variation for some loci. The extent and physical location of polymorphism within and between AMF genomes is unclear. We used two complementary strategies to estimate genetic diversity in AMF, investigating polymorphism both on a genome scale and in putative single copy loci. First, we used data from whole-genome pyrosequencing of four AMF isolates to describe genetic diversity, based on a conservative network-based clustering approach. AMF isolates showed marked differences in genome-wide diversity patterns in comparison to a panel of control fungal genomes. This clustering approach further allowed us to provide conservative estimates of Rhizophagus spp. genomes sizes. Second, we designed new putative single copy genomic markers, which we investigated by massive parallel amplicon sequencing for two Rhizophagus irregularis and one Rhizophagus sp. isolates. Most loci showed high polymorphism, with up to 103 alleles per marker. This polymorphism could be distributed within or between nuclei. However, we argue that the Rhizophagus isolates under study might be heterokaryotic, at least for the putative single copy markers we studied. Considering that genetic information is the main resource for identification of AMF, we suggest that special attention is warranted for the study of these ecologically important organisms.}, } @article {pmid25562138, year = {2015}, author = {Gomes, AP and Blenis, J}, title = {A nexus for cellular homeostasis: the interplay between metabolic and signal transduction pathways.}, journal = {Current opinion in biotechnology}, volume = {34}, number = {}, pages = {110-117}, pmid = {25562138}, issn = {1879-0429}, support = {HL121266/HL/NHLBI NIH HHS/United States ; R01 HL121266/HL/NHLBI NIH HHS/United States ; R01 CA046595/CA/NCI NIH HHS/United States ; R37 CA046595/CA/NCI NIH HHS/United States ; CA46595/CA/NCI NIH HHS/United States ; R01 GM051405/GM/NIGMS NIH HHS/United States ; GM51405/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Homeostasis ; Metabolic Networks and Pathways ; Protein Kinases/metabolism ; *Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {In multicellular organisms, individual cells have evolved to sense external and internal cues in order to maintain cellular homeostasis and survive under different environmental conditions. Cells efficiently adjust their metabolism to reflect the abundance of nutrients, energy and growth factors. The ability to rewire cellular metabolism between anabolic and catabolic processes is crucial for cells to thrive. Thus, cells have developed, through evolution, metabolic networks that are highly plastic and tightly regulated to meet the requirements necessary to maintain cellular homeostasis. The plasticity of these cellular systems is tightly regulated by complex signaling networks that integrate the intracellular and extracellular information. The coordination of signal transduction and metabolic pathways is essential in maintaining a healthy and rapidly responsive cellular state.}, } @article {pmid25558847, year = {2015}, author = {Boileau, E and George, CH and Parthimos, D and Mitchell, AN and Aziz, S and Nithiarasu, P}, title = {Synergy Between Intercellular Communication and Intracellular Ca(2+) Handling in Arrhythmogenesis.}, journal = {Annals of biomedical engineering}, volume = {43}, number = {7}, pages = {1614-1625}, doi = {10.1007/s10439-014-1243-x}, pmid = {25558847}, issn = {1573-9686}, support = {094219/Z/10/Z//Wellcome Trust/United Kingdom ; FS/06/082/21723//British Heart Foundation/United Kingdom ; FS/09/028/27602//British Heart Foundation/United Kingdom ; }, mesh = {Animals ; Arrhythmias, Cardiac/*physiopathology ; Calcium/*physiology ; Cell Communication/*physiology ; Cell Line ; Mice ; }, abstract = {Calcium is the primary signalling component of excitation-contraction coupling, the process linking electrical excitability of cardiac muscle cells to coordinated contraction of the heart. Understanding [Formula: see text] handling processes at the cellular level and the role of intercellular communication in the emergence of multicellular synchronization are key aspects in the study of arrhythmias. To probe these mechanisms, we have simulated cellular interactions on large scale arrays that mimic cardiac tissue, and where individual cells are represented by a mathematical model of intracellular [Formula: see text] dynamics. Theoretical predictions successfully reproduced experimental findings and provide novel insights on the action of two pharmacological agents (ionomycin and verapamil) that modulate [Formula: see text] signalling pathways via distinct mechanisms. Computational results have demonstrated how transitions between local synchronisation events and large scale wave formation are affected by these agents. Entrainment phenomena are shown to be linked to both intracellular [Formula: see text] and coupling-specific dynamics in a synergistic manner. The intrinsic variability of the cellular matrix is also shown to affect emergent patterns of rhythmicity, providing insights into the origins of arrhythmogenic [Formula: see text] perturbations in cardiac tissue in situ.}, } @article {pmid25552080, year = {2014}, author = {Akhmadeev, AV and Kalimullina, LB}, title = {[Structural and functional organization of cart peptide-expressing neurons in brain amygdala].}, journal = {Morfologiia (Saint Petersburg, Russia)}, volume = {146}, number = {4}, pages = {11-14}, pmid = {25552080}, issn = {1026-3543}, mesh = {Amygdala/*cytology/*metabolism ; Animals ; Dendrites/*metabolism ; Gene Expression Regulation/*physiology ; Nerve Tissue Proteins/*biosynthesis ; Rats ; Rats, Wistar ; }, abstract = {The aim of the study was to identify the specific features of structural and functional organization of the neurons in dorsomedial nucleus of amygdala containing immunoreactive CART peptide. The study was carried out on 15 Wistar rats using an immunocytochemical demonstration of CART peptide and Golgi method. CART peptide-expressing neurons in subependymal zone of the nucleus were shown to be neuroblastoformal, while those located in its central zones were short-dendritic. These data demonstrate that CART peptide-expressing neurons are belong to a sparcely branched neuronal system. The results obtained in this work together with the analysis of the literature and the provisions of A.L. Polenov (1993) concept on the origin and evolution of the neuroendocrine cells and neurohormonal regulation in Metazoa, suggest that CART peptide appeared during the early stages of the formation of the regulatory chemical communication in the multicellular organisms.}, } @article {pmid25551152, year = {2015}, author = {Duran-Nebreda, S and Solé, R}, title = {Emergence of multicellularity in a model of cell growth, death and aggregation under size-dependent selection.}, journal = {Journal of the Royal Society, Interface}, volume = {12}, number = {102}, pages = {20140982}, pmid = {25551152}, issn = {1742-5662}, mesh = {Algorithms ; Apoptosis ; *Biological Evolution ; Cluster Analysis ; Computer Simulation ; Models, Biological ; Mutation ; Phylogeny ; Saccharomyces cerevisiae/*genetics/*physiology ; Selection, Genetic ; }, abstract = {How multicellular life forms evolved from unicellular ones constitutes a major problem in our understanding of the evolution of our biosphere. A recent set of experiments involving yeast cell populations have shown that selection for faster sedimenting cells leads to the appearance of stable aggregates of cells that are able to split into smaller clusters. It was suggested that the observed evolutionary patterns could be the result of evolved programmes affecting cell death. Here, we show, using a simple model of cell-cell interactions and evolving adhesion rates, that the observed patterns in cluster size and localized mortality can be easily interpreted in terms of waste accumulation and toxicity-driven apoptosis. This simple mechanism would have played a key role in the early evolution of multicellular life forms based on both aggregative and clonal development. The potential extensions of this work and its implications for natural and synthetic multicellularity are discussed.}, } @article {pmid25547403, year = {2015}, author = {Messina, G and Celauro, E and Atterrato, MT and Giordano, E and Iwashita, S and Dimitri, P}, title = {The Bucentaur (BCNT) protein family: a long-neglected class of essential proteins required for chromatin/chromosome organization and function.}, journal = {Chromosoma}, volume = {124}, number = {2}, pages = {153-162}, pmid = {25547403}, issn = {1432-0886}, mesh = {Amino Acid Sequence ; Animals ; Carrier Proteins/genetics/metabolism ; Chickens/genetics ; Chromatin/*genetics ; Drosophila/genetics ; Drosophila Proteins/genetics/metabolism ; Evolution, Molecular ; Extracellular Matrix Proteins/*genetics/metabolism ; Gene Expression Regulation, Developmental ; Humans ; Mice ; Molecular Sequence Data ; *Multigene Family ; Nuclear Proteins ; Phosphoproteins/*genetics/metabolism ; Saccharomyces cerevisiae/genetics ; Sequence Alignment ; Zebrafish/genetics ; }, abstract = {The evolutionarily conserved Bucentaur (BCNT) protein superfamily was identified about two decades ago in bovines, but its biological role has long remained largely unknown. Sparse studies in the literature suggest that BCNT proteins perform important functions during development. Only recently, a functional analysis of the Drosophila BCNT ortholog, called YETI, has provided evidence that it is essential for proper fly development and plays roles in chromatin organization. Here, we introduce the BCNT proteins and comprehensively review data that contribute to clarify their function and mechanistic clues on how they may control development in multicellular organisms.}, } @article {pmid25540429, year = {2015}, author = {Meller, J and Rogozin, IB and Poliakov, E and Meller, N and Bedanov-Pack, M and Plow, EF and Qin, J and Podrez, EA and Byzova, TV}, title = {Emergence and subsequent functional specialization of kindlins during evolution of cell adhesiveness.}, journal = {Molecular biology of the cell}, volume = {26}, number = {4}, pages = {786-796}, pmid = {25540429}, issn = {1939-4586}, support = {R01 HL071625/HL/NHLBI NIH HHS/United States ; //Intramural NIH HHS/United States ; R01 HL058758/HL/NHLBI NIH HHS/United States ; P01 HL073311/HL/NHLBI NIH HHS/United States ; R01 HL096062/HL/NHLBI NIH HHS/United States ; HL073311/HL/NHLBI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Biological Evolution ; Cell Adhesion ; Conserved Sequence ; Evolution, Molecular ; Genome ; Humans ; Integrins/genetics/metabolism/*physiology ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Sequence Alignment ; Sequence Analysis, Protein ; Species Specificity ; Talin/genetics/metabolism/*physiology ; }, abstract = {Kindlins are integrin-interacting proteins essential for integrin-mediated cell adhesiveness. In this study, we focused on the evolutionary origin and functional specialization of kindlins as a part of the evolutionary adaptation of cell adhesive machinery. Database searches revealed that many members of the integrin machinery (including talin and integrins) existed before kindlin emergence in evolution. Among the analyzed species, all metazoan lineages—but none of the premetazoans—had at least one kindlin-encoding gene, whereas talin was present in several premetazoan lineages. Kindlin appears to originate from a duplication of the sequence encoding the N-terminal fragment of talin (the talin head domain) with a subsequent insertion of the PH domain of separate origin. Sequence analysis identified a member of the actin filament-associated protein 1 (AFAP1) superfamily as the most likely origin of the kindlin PH domain. The functional divergence between kindlin paralogues was assessed using the sequence swap (chimera) approach. Comparison of kindlin 2 (K2)/kindlin 3 (K3) chimeras revealed that the F2 subdomain, in particular its C-terminal part, is crucial for the differential functional properties of K2 and K3. The presence of this segment enables K2 but not K3 to localize to focal adhesions. Sequence analysis of the C-terminal part of the F2 subdomain of K3 suggests that insertion of a variable glycine-rich sequence in vertebrates contributed to the loss of constitutive K3 targeting to focal adhesions. Thus emergence and subsequent functional specialization of kindlins allowed multicellular organisms to develop additional tissue-specific adaptations of cell adhesiveness.}, } @article {pmid25540145, year = {2015}, author = {Rossier, BC and Baker, ME and Studer, RA}, title = {Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited.}, journal = {Physiological reviews}, volume = {95}, number = {1}, pages = {297-340}, doi = {10.1152/physrev.00011.2014}, pmid = {25540145}, issn = {1522-1210}, mesh = {Aldosterone/*metabolism ; Animals ; *Biological Evolution ; Epithelial Sodium Channels/chemistry/genetics/*metabolism ; Genome, Human ; Humans ; Nephrons/physiology ; Signal Transduction/physiology ; Sodium/*metabolism ; Sodium-Potassium-Exchanging ATPase/chemistry/genetics/*metabolism ; }, abstract = {Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases.}, } @article {pmid25538686, year = {2014}, author = {Soto, W and Nishiguchi, MK}, title = {Microbial experimental evolution as a novel research approach in the Vibrionaceae and squid-Vibrio symbiosis.}, journal = {Frontiers in microbiology}, volume = {5}, number = {}, pages = {593}, pmid = {25538686}, issn = {1664-302X}, support = {SC1 AI081659/AI/NIAID NIH HHS/United States ; }, abstract = {The Vibrionaceae are a genetically and metabolically diverse family living in aquatic habitats with a great propensity toward developing interactions with eukaryotic microbial and multicellular hosts (as either commensals, pathogens, and mutualists). The Vibrionaceae frequently possess a life history cycle where bacteria are attached to a host in one phase and then another where they are free from their host as either part of the bacterioplankton or adhered to solid substrates such as marine sediment, riverbeds, lakebeds, or floating particulate debris. These two stages in their life history exert quite distinct and separate selection pressures. When bound to solid substrates or to host cells, the Vibrionaceae can also exist as complex biofilms. The association between bioluminescent Vibrio spp. and sepiolid squids (Cephalopoda: Sepiolidae) is an experimentally tractable model to study bacteria and animal host interactions, since the symbionts and squid hosts can be maintained in the laboratory independently of one another. The bacteria can be grown in pure culture and the squid hosts raised gnotobiotically with sterile light organs. The partnership between free-living Vibrio symbionts and axenic squid hatchlings emerging from eggs must be renewed every generation of the cephalopod host. Thus, symbiotic bacteria and animal host can each be studied alone and together in union. Despite virtues provided by the Vibrionaceae and sepiolid squid-Vibrio symbiosis, these assets to evolutionary biology have yet to be fully utilized for microbial experimental evolution. Experimental evolution studies already completed are reviewed, along with exploratory topics for future study.}, } @article {pmid25525215, year = {2015}, author = {Grau-Bové, X and Sebé-Pedrós, A and Ruiz-Trillo, I}, title = {The eukaryotic ancestor had a complex ubiquitin signaling system of archaeal origin.}, journal = {Molecular biology and evolution}, volume = {32}, number = {3}, pages = {726-739}, pmid = {25525215}, issn = {1537-1719}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Cluster Analysis ; Eukaryota/*genetics ; *Evolution, Molecular ; Genes/genetics ; Genes, Archaeal/*genetics ; Phylogeny ; Small Ubiquitin-Related Modifier Proteins/*genetics ; Ubiquitin/*genetics ; }, abstract = {The origin of the eukaryotic cell is one of the most important transitions in the history of life. However, the emergence and early evolution of eukaryotes remains poorly understood. Recent data have shown that the last eukaryotic common ancestor (LECA) was much more complex than previously thought. The LECA already had the genetic machinery encoding the endomembrane apparatus, spliceosome, nuclear pore, and myosin and kinesin cytoskeletal motors. It is unclear, however, when the functional regulation of these cellular components evolved. Here, we address this question by analyzing the origin and evolution of the ubiquitin (Ub) signaling system, one of the most important regulatory layers in eukaryotes. We delineated the evolution of the whole Ub, Small-Ub-related MOdifier (SUMO), and Ub-fold modifier 1 (Ufm1) signaling networks by analyzing representatives from all major eukaryotic, bacterial, and archaeal lineages. We found that the Ub toolkit had a pre-eukaryotic origin and is present in three extant archaeal groups. The pre-eukaryotic Ub toolkit greatly expanded during eukaryogenesis, through massive gene innovation and diversification of protein domain architectures. This resulted in a LECA with essentially all of the Ub-related genes, including the SUMO and Ufm1 Ub-like systems. Ub and SUMO signaling further expanded during eukaryotic evolution, especially labeling and delabeling enzymes responsible for substrate selection. Additionally, we analyzed protein domain architecture evolution and found that multicellular lineages have the most complex Ub systems in terms of domain architectures. Together, we demonstrate that the Ub system predates the origin of eukaryotes and that a burst of innovation during eukaryogenesis led to a LECA with complex posttranslational regulation.}, } @article {pmid25498309, year = {2015}, author = {Cai, X and Wang, X and Patel, S and Clapham, DE}, title = {Insights into the early evolution of animal calcium signaling machinery: a unicellular point of view.}, journal = {Cell calcium}, volume = {57}, number = {3}, pages = {166-173}, pmid = {25498309}, issn = {1532-1991}, support = {/HHMI/Howard Hughes Medical Institute/United States ; BB/G013721/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Calcium Signaling/*physiology ; Eukaryota/*metabolism ; Fungi/*metabolism ; Phylogeny ; Plants/*metabolism ; }, abstract = {The basic principles of Ca(2+) regulation emerged early in prokaryotes. Ca(2+) signaling acquired more extensive and varied functions when life evolved into multicellular eukaryotes with intracellular organelles. Animals, fungi and plants display differences in the mechanisms that control cytosolic Ca(2+) concentrations. The aim of this review is to examine recent findings from comparative genomics of Ca(2+) signaling molecules in close unicellular relatives of animals and in common unicellular ancestors of animals and fungi. Also discussed are the evolution and origins of the sperm-specific CatSper channel complex, cation/Ca(2+) exchangers and four-domain voltage-gated Ca(2+) channels. Newly identified evolutionary evidence suggests that the distinct Ca(2+) signaling machineries in animals, plants and fungi likely originated from an ancient Ca(2+) signaling machinery prior to early eukaryotic radiation.}, } @article {pmid25487147, year = {2015}, author = {Hashimshony, T and Feder, M and Levin, M and Hall, BK and Yanai, I}, title = {Spatiotemporal transcriptomics reveals the evolutionary history of the endoderm germ layer.}, journal = {Nature}, volume = {519}, number = {7542}, pages = {219-222}, pmid = {25487147}, issn = {1476-4687}, support = {310927/ERC_/European Research Council/International ; }, mesh = {Animals ; Caenorhabditis elegans/cytology/*embryology/*genetics ; Cell Lineage ; Eating ; Ectoderm/cytology/embryology/metabolism ; Endoderm/cytology/embryology/*metabolism ; *Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Developmental/*genetics ; Mesoderm/cytology/embryology/metabolism ; Models, Biological ; Porifera/cytology/embryology/genetics ; Sea Anemones/cytology/embryology/genetics ; *Spatio-Temporal Analysis ; Time Factors ; Transcriptome/*genetics ; Xenopus/embryology/genetics ; }, abstract = {The concept of germ layers has been one of the foremost organizing principles in developmental biology, classification, systematics and evolution for 150 years (refs 1 - 3). Of the three germ layers, the mesoderm is found in bilaterian animals but is absent in species in the phyla Cnidaria and Ctenophora, which has been taken as evidence that the mesoderm was the final germ layer to evolve. The origin of the ectoderm and endoderm germ layers, however, remains unclear, with models supporting the antecedence of each as well as a simultaneous origin. Here we determine the temporal and spatial components of gene expression spanning embryonic development for all Caenorhabditis elegans genes and use it to determine the evolutionary ages of the germ layers. The gene expression program of the mesoderm is induced after those of the ectoderm and endoderm, thus making it the last germ layer both to evolve and to develop. Strikingly, the C. elegans endoderm and ectoderm expression programs do not co-induce; rather the endoderm activates earlier, and this is also observed in the expression of endoderm orthologues during the embryology of the frog Xenopus tropicalis, the sea anemone Nematostella vectensis and the sponge Amphimedon queenslandica. Querying the phylogenetic ages of specifically expressed genes reveals that the endoderm comprises older genes. Taken together, we propose that the endoderm program dates back to the origin of multicellularity, whereas the ectoderm originated as a secondary germ layer freed from ancestral feeding functions.}, } @article {pmid25486567, year = {2014}, author = {Iranzo, J and Lobkovsky, AE and Wolf, YI and Koonin, EV}, title = {Virus-host arms race at the joint origin of multicellularity and programmed cell death.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {13}, number = {19}, pages = {3083-3088}, pmid = {25486567}, issn = {1551-4005}, support = {//Intramural NIH HHS/United States ; }, mesh = {*Apoptosis ; Biological Evolution ; Eukaryota/*physiology ; *Models, Biological ; Viruses/metabolism/*pathogenicity ; }, abstract = {Unicellular eukaryotes and most prokaryotes possess distinct mechanisms of programmed cell death (PCD). How an "altruistic" trait, such as PCD, could evolve in unicellular organisms? To address this question, we developed a mathematical model of the virus-host co-evolution that involves interaction between immunity, PCD and cellular aggregation. Analysis of the parameter space of this model shows that under high virus load and imperfect immunity, joint evolution of cell aggregation and PCD is the optimal evolutionary strategy. Given the abundance of viruses in diverse habitats and the wide spread of PCD in most organisms, these findings imply that multiple instances of the emergence of multicellularity and its essential attribute, PCD, could have been driven, at least in part, by the virus-host arms race.}, } @article {pmid25483255, year = {2014}, author = {Bocksberger, M and Karch, F and Gibert, JM}, title = {In vivo analysis of a fluorescent SUMO fusion in transgenic Drosophila.}, journal = {Fly}, volume = {8}, number = {2}, pages = {108-112}, pmid = {25483255}, issn = {1933-6942}, mesh = {Animals ; Animals, Genetically Modified ; Drosophila ; *Luminescent Proteins ; Polytene Chromosomes/chemistry ; Recombinant Fusion Proteins/analysis ; SUMO-1 Protein/*analysis ; }, abstract = {Sumoylation, the covalent attachment of SUMO, a 90 amino acid peptide related to ubiquitin, is a major modulator of protein functions. Fluorescent SUMO protein fusions have been used in cell cultures to visualize SUMO in vivo but not in multicellular organisms. We generated a transgenic line of Drosophila expressing an mCherry-SUMO fusion. We analyzed its pattern in vivo in salivary gland nuclei expressing Venus-HP1 to recognize the different chromatin components (Chromocenter, chromosome IV). We compared it to SUMO immunostaining on squashed polytene chromosomes and observed similar patterns. In addition to the previously reported SUMO localizations (chromosome arms and chromocenter), we identify 2 intense binding sites: the fourth chromosome telomere and the DAPI-bright band in the region 81F.}, } @article {pmid25477895, year = {2014}, author = {Domozych, DS and Domozych, CE}, title = {Multicellularity in green algae: upsizing in a walled complex.}, journal = {Frontiers in plant science}, volume = {5}, number = {}, pages = {649}, pmid = {25477895}, issn = {1664-462X}, abstract = {Modern green algae constitute a large and diverse taxonomic assemblage that encompasses many multicellular phenotypes including colonial, filamentous, and parenchymatous forms. In all multicellular green algae, each cell is surrounded by an extracellular matrix (ECM), most often in the form of a cell wall. Volvocalean taxa like Volvox have an elaborate, gel-like, hydroxyproline rich glycoprotein covering that contains the cells of the colony. In "ulvophytes," uronic acid-rich and sulfated polysaccharides are the likely adhesion agents that maintain the multicellular habit. Charophytes also produce polysaccharide-rich cell walls and in late divergent taxa, pectin plays a critical role in cell adhesion in the multicellular complex. Cell walls are products of coordinated interaction of membrane trafficking, cytoskeletal dynamics and the cell's signal transduction machinery responding both to precise internal clocks and external environmental cues. Most often, these activities must be synchronized with the secretion, deposition and remodeling of the polymers of the ECM. Rapid advances in molecular genetics, cell biology and cell wall biochemistry of green algae will soon provide new insights into the evolution and subcellular processes leading to multicellularity.}, } @article {pmid25477034, year = {2014}, author = {Yuan, W and Liu, Y and Lok, JB and Stoltzfus, JD and Gasser, RB and Lei, W and Fang, R and Zhao, J and Hu, M}, title = {Exploring features and function of Ss-riok-3, an enigmatic kinase gene from Strongyloides stercoralis.}, journal = {Parasites & vectors}, volume = {7}, number = {}, pages = {561}, pmid = {25477034}, issn = {1756-3305}, support = {AI-105856/AI/NIAID NIH HHS/United States ; R21 AI105856/AI/NIAID NIH HHS/United States ; R01 AI050668/AI/NIAID NIH HHS/United States ; AI-050688/AI/NIAID NIH HHS/United States ; R01 AI082548/AI/NIAID NIH HHS/United States ; AI-082548/AI/NIAID NIH HHS/United States ; R33 AI105856/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animal Structures/enzymology ; Animals ; Cluster Analysis ; DNA, Complementary/genetics/isolation & purification ; Gene Expression Profiling ; Microscopy, Fluorescence ; Molecular Sequence Data ; Open Reading Frames ; Phylogeny ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Protein Serine-Threonine Kinases/*genetics ; Sequence Alignment ; Sequence Homology ; Strongyloides stercoralis/*enzymology/genetics/growth & development ; }, abstract = {BACKGROUND: Right open reading frame protein kinase 3 (RIOK-3) belongs to the atypical kinase family. Unlike the other two members, RIOK-1 and RIOK-2, which are conserved from Archaea to humans, RIOK-3 occurs only in multicellular organisms. Studies on HeLa cells indicate that human RIOK-3 is a component of the 40S small ribosome subunit and supports cancer cell growth and survival. However, almost nothing is known about the function of RIOK-3. We explored the functional role of RIOK-3 encoding gene from Strongyloides stercoralis, a parasitic nematode of humans and dogs.

METHODS: To analyze the gene and promoter structure of Ss-riok-3, RACE-PCR and Genome-walker PCR were performed to isolate the full length cDNA, gDNA and promoter region of Ss-riok-3. RNA-seq was conducted to assess the transcript abundance of Ss-riok-3 in different stages of S. stercoralis. Transgenesis was employed to determine the anatomic expression patterns of Ss-riok-3.

RESULTS: The RIOK-3 protein-encoding gene (designated Ss-riok-3) of S. stercoralis was characterized. The full-length complementary and genomic DNAs of the RIOK-3 encoding gene (riok-3) were isolated from this nematode. The cDNA of Ss-riok-3 is 1,757 bp in length, including a 23 bp 5'-UTR, a 36 bp 3'-UTR and a 1,698 bp coding region encoding a protein of 565 amino acids (aa) containing a RIO kinase domain. RNA sequencing (RNA-seq) analysis revealed that Ss-riok-3 is transcribed in all developmental stages of S. stercoralis assessed, with transcripts being particularly abundant in parasitic females. Gene structure analysis revealed that Ss-riok-3 contains no intron. The putative promoter contains conserved promoter elements, including four TATA, two GATA, one inverse GATA and one inverse CAAT boxes. The promoter of Ss-riok-3 drives GFP expression in the head neuron, intestine and body wall muscle of transgenic S. stercoralis larvae, and the TATA boxes present in the 3'-UTR of the gene immediately upstream of Ss-riok-3 initiate transcription.

CONCLUSIONS: The characterization of the RIOK-3 encoding gene from S. stercoralis provides a sound foundation for investigating in detail its function in the development and reproduction of this important pathogen.}, } @article {pmid25474005, year = {2014}, author = {Arnoult, LA}, title = {[The genetic walk of evolution].}, journal = {Biologie aujourd'hui}, volume = {208}, number = {3}, pages = {237-249}, doi = {10.1051/jbio/2014027}, pmid = {25474005}, issn = {2105-0686}, mesh = {Adaptation, Biological/genetics ; Animals ; Animals, Laboratory ; Directed Molecular Evolution ; Drosophila/genetics ; *Evolution, Molecular ; Humans ; Selection, Genetic ; }, abstract = {Genetic mutations are the main fuel of evolution. In each generation, they produce new variations, which may be sorted out by natural or sexual selection. Mutations are generated by chance; yet which are the mutations actually sorted out by evolution, and why? This review presents some recent advances regarding this question. First, we gather results obtained at molecular and cellular levels, through synthetic experiments and under artificial selection paradigms. Next, we highlight studies at the multi-cellular level, especially studies of repeated evolution, whereby independent lineages acquire similar traits. Recent meta-analysis and quantifications are being presented; together they suggest that evolutionary relevant mutations accumulate around hotspots, spanning different levels of genetic organization. Pioneering work suggests that many causes, corresponding to many biological contexts, may explain the existence of these genetic hotspots. We finally discuss methodological limits, empirical challenges and a few future potential directions for this domain of research dedicated to the genetic path of evolution.}, } @article {pmid25457940, year = {2014}, author = {Reece, SE and Mideo, N}, title = {Malaria parasites prepare for flight.}, journal = {Trends in parasitology}, volume = {30}, number = {12}, pages = {551-553}, doi = {10.1016/j.pt.2014.10.004}, pmid = {25457940}, issn = {1471-5007}, mesh = {*Adaptation, Physiological ; Animals ; Culicidae/parasitology ; Female ; Host-Parasite Interactions/*physiology ; Humans ; Life Cycle Stages/physiology ; Malaria/*parasitology/*transmission ; Male ; Plasmodium/*physiology ; Seasons ; Sex Ratio ; }, abstract = {Life in seasonal environments often means facing extreme environmental fluctuations. Many multicellular organisms have evolved strategies to cope with this lifestyle. Single-celled malaria parasites are no different. An elegant experiment reveals that they respond to the availability of mosquitoes to make the most of seasonal transmission opportunities.}, } @article {pmid25457111, year = {2015}, author = {Van Hautegem, T and Waters, AJ and Goodrich, J and Nowack, MK}, title = {Only in dying, life: programmed cell death during plant development.}, journal = {Trends in plant science}, volume = {20}, number = {2}, pages = {102-113}, doi = {10.1016/j.tplants.2014.10.003}, pmid = {25457111}, issn = {1878-4372}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Apoptosis ; Arabidopsis/growth & development/physiology ; Gene Expression Regulation, Developmental/genetics ; Gene Expression Regulation, Plant/*genetics ; Oryza/growth & development/physiology ; Plant Development/genetics/*physiology ; Zea mays/growth & development/physiology ; }, abstract = {Programmed cell death (PCD) is a fundamental process of life. During the evolution of multicellular organisms, the actively controlled demise of cells has been recruited to fulfil a multitude of functions in development, differentiation, tissue homeostasis, and immune systems. In this review we discuss some of the multiple cases of PCD that occur as integral parts of plant development in a remarkable variety of cell types, tissues, and organs. Although research in the last decade has discovered a number of PCD regulators, mediators, and executers, we are still only beginning to understand the mechanistic complexity that tightly controls preparation, initiation, and execution of PCD as a process that is indispensable for successful vegetative and reproductive development of plants.}, } @article {pmid25448004, year = {2014}, author = {Viaene, T and Landberg, K and Thelander, M and Medvecka, E and Pederson, E and Feraru, E and Cooper, ED and Karimi, M and Delwiche, CF and Ljung, K and Geisler, M and Sundberg, E and Friml, J}, title = {Directional auxin transport mechanisms in early diverging land plants.}, journal = {Current biology : CB}, volume = {24}, number = {23}, pages = {2786-2791}, doi = {10.1016/j.cub.2014.09.056}, pmid = {25448004}, issn = {1879-0445}, abstract = {The emergence and radiation of multicellular land plants was driven by crucial innovations to their body plans. The directional transport of the phytohormone auxin represents a key, plant-specific mechanism for polarization and patterning in complex seed plants. Here, we show that already in the early diverging land plant lineage, as exemplified by the moss Physcomitrella patens, auxin transport by PIN transporters is operational and diversified into ER-localized and plasma membrane-localized PIN proteins. Gain-of-function and loss-of-function analyses revealed that PIN-dependent intercellular auxin transport in Physcomitrella mediates crucial developmental transitions in tip-growing filaments and waves of polarization and differentiation in leaf-like structures. Plasma membrane PIN proteins localize in a polar manner to the tips of moss filaments, revealing an unexpected relation between polarization mechanisms in moss tip-growing cells and multicellular tissues of seed plants. Our results trace the origins of polarization and auxin-mediated patterning mechanisms and highlight the crucial role of polarized auxin transport during the evolution of multicellular land plants.}, } @article {pmid25445586, year = {2014}, author = {Zhao, BF and Zhao, ZJ}, title = {Molecular cloning and characterization of a tyrosine phosphatase from Monosiga brevicollis.}, journal = {Biochemical and biophysical research communications}, volume = {453}, number = {4}, pages = {761-766}, doi = {10.1016/j.bbrc.2014.10.019}, pmid = {25445586}, issn = {1090-2104}, support = {HL079441/HL/NHLBI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Choanoflagellata/classification/*enzymology ; Cloning, Molecular/methods ; Enzyme Activation ; Molecular Sequence Data ; Protein Tyrosine Phosphatases/*chemistry/genetics/*metabolism ; Recombinant Proteins/chemistry/metabolism ; Species Specificity ; Substrate Specificity ; }, abstract = {Protein tyrosine phosphorylation is thought to be a unique feature of multicellular animals. Interestingly, the genome of the unicellular protist Monosiga brevicollis reveals a surprisingly high number and diversity of protein tyrosine kinases, protein tyrosine phosphatases (PTPs), and phosphotyrosine-binding domains. Our study focuses on a hypothetical SH2 domain-containing PTP (SHP), which interestingly has a predicted structure that is distinct from SHPs found in animals. In this study, we isolated cDNA of the enzyme and discovered that its actual sequence was different from the predicted sequence as a result of non-consensus RNA splicing. Contrary to the predicted structure with one SH2 domain and a disrupted phosphatase domain, Monosiga brevicollis SHP (MbSHP) contains two SH2 domains and an intact PTP domain, closely resembling SHP enzymes found in animals. We further expressed the full-length and SH2 domain-truncated forms of the enzyme in Escherichiacoli cells and characterized their enzymatic activities. The double-SH2 domain-truncated form of the enzyme effectively dephosphorylated a common PTP substrate with a specific activity among the highest in characterized PTPs, while the full-length and the N-terminal SH2 domain-truncated forms of the enzyme showed much lower activity with altered pH dependency and responses to ionic strength and common PTP inhibitors. This indicates that SH2 domains suppress the catalytic activity. SHP represents a highly conserved ancient PTP, and studying MbSHP should provide a better understanding about the evolution of tyrosine phosphorylation.}, } @article {pmid25438594, year = {2013}, author = {Khokhlov, AN}, title = {[Impairment of regeneration in aging: appropriateness or stochastics?].}, journal = {Ontogenez}, volume = {44}, number = {6}, pages = {434-440}, pmid = {25438594}, issn = {0475-1450}, mesh = {Aging/*metabolism/pathology ; Cell Differentiation ; Cell Transformation, Neoplastic/metabolism/pathology ; Cellular Senescence ; Humans ; *Models, Biological ; *Regeneration ; }, abstract = {There is a viewpoint that suppression of the proliferative capacity of cells and impairment of the regeneration of tissues and organs in aging are a consequence of specially arisen during evolution mechanisms that reduce the risk of malignant transformation and, thus, protect against cancer. At the same time, senescent cells of the body begin to accumulate a variety of macromolecular defects, which, conversely, increase the likelihood of their transformation into cancer cells. Thus, according to the point, the restriction of cell proliferation is a double-edged sword, which, on the one hand, reduces the likelihood of developing cancer at an early age, but on the other hand--limits life span due to the accumulation of "damaged" cells in old age. However, it remains unclear why normal human cells in vitro, with none of the mentioned "anticancer" barriers functioning at the organismal level only, NEVER undergo spontaneous malignant transformation. In addition, it is also unclear how the freshwater hydra which, under certain conditions, has really no postmitotic and senescent cells, escapes both aging and cancer and, at such conditions (excluding the need for sexual reproduction), can live almost indefinitely, having a great regenerative potential (new organism can arise even from a 1/100 of the old one). I believe that the restriction of cell proliferation in an aging multicellular organism is not a consequence of implementing a special program. Apparently, there is no special program of aging. It is only a "byproduct" of the program of development, implementation of which in higher organisms suggests the need for the emergence of cell populations with very low or even zero proliferative activity, which determines the limited capacity of relevant organs and tissues to regenerate. At the same time, it is the presence of highly differentiated cell populations, barely able or completely unable to reproduce (neurons, cardiomyocytes, hepatocytes), that ensures the normal functioning of the higher animals and humans. Even the regeneration of these organs with the help of stem cells could lead to a breach of the necessary interactions in complex systems. Reductionism in experimental-gerontological research ("everything is determined by deleterious changes in single cells") that has become widespread in recent decades, stimulated the emergence of a number of model systems for studying mechanisms of aging in isolated cells (Hayflick phenomenon, the model of "stationary phase aging", the cell-kinetic model for testing geroprotectors and geropromoters, etc.). However, at present it seems that the data obtained in such models cannot be automatically applied to the situation in the whole organism. Apparently, the impairment of regulatory processes, realized at the neurohumoral level, still plays the main role in the mechanisms of aging of multicellular organisms, not just the accumulation of macromolecular defects in individual cells. It is possible that it is the deterioration of such regulation that may be the cause of the observed abnormal INCREASE of the intensity of proliferation of some cell populations in old age, resulting in senile acromegaly and age-related rise of numerous benign tumors. It seems that the quality of the cells themselves does not worsen with age as much as reliability of the organism CONTROL over cells, organs and tissues, which leads to an increase in the probability of death.}, } @article {pmid25436741, year = {2013}, author = {Baniahmad, A}, title = {Why do we need to age?.}, journal = {Hormone molecular biology and clinical investigation}, volume = {16}, number = {1}, pages = {3-5}, doi = {10.1515/hmbci-2013-0030}, pmid = {25436741}, issn = {1868-1891}, abstract = {Abstract A key question remains: why do multicellular organisms have a limited lifespan? The aging process is considered to be a decline of keeping the molecular, cellular and organ structure and interactions upright. It is hypothesized here that an evolutionary force has actively selected for limited lifespan and prior to that there is the process of aging. Many theories exist, including the endocrine theory of aging and reproduction-based aging. Here, a hypothesis is deduced for the driving force of the evolution of aging and lifespan limitation.}, } @article {pmid25435097, year = {2015}, author = {Horn, T and Adel, S and Schumann, R and Sur, S and Kakularam, KR and Polamarasetty, A and Redanna, P and Kuhn, H and Heydeck, D}, title = {Evolutionary aspects of lipoxygenases and genetic diversity of human leukotriene signaling.}, journal = {Progress in lipid research}, volume = {57}, number = {}, pages = {13-39}, pmid = {25435097}, issn = {1873-2194}, mesh = {Animals ; Evolution, Molecular ; *Genetic Variation ; Humans ; Leukotrienes/*metabolism ; Lipoxygenases/*genetics/*metabolism ; Phylogeny ; Receptors, Leukotriene/genetics/metabolism ; *Signal Transduction ; Vertebrates/metabolism ; }, abstract = {Leukotrienes are pro-inflammatory lipid mediators, which are biosynthesized via the lipoxygenase pathway of the arachidonic acid cascade. Lipoxygenases form a family of lipid peroxidizing enzymes and human lipoxygenase isoforms have been implicated in the pathogenesis of inflammatory, hyperproliferative (cancer) and neurodegenerative diseases. Lipoxygenases are not restricted to humans but also occur in a large number of pro- and eucaryotic organisms. Lipoxygenase-like sequences have been identified in the three domains of life (bacteria, archaea, eucarya) but because of lacking functional data the occurrence of catalytically active lipoxygenases in archaea still remains an open question. Although the physiological and/or pathophysiological functions of various lipoxygenase isoforms have been studied throughout the last three decades there is no unifying concept for the biological importance of these enzymes. In this review we are summarizing the current knowledge on the distribution of lipoxygenases in living single and multicellular organisms with particular emphasis to higher vertebrates and will also focus on the genetic diversity of enzymes and receptors involved in human leukotriene signaling.}, } @article {pmid25433524, year = {2014}, author = {Leiman, SA and Arboleda, LC and Spina, JS and McLoon, AL}, title = {SinR is a mutational target for fine-tuning biofilm formation in laboratory-evolved strains of Bacillus subtilis.}, journal = {BMC microbiology}, volume = {14}, number = {}, pages = {301}, pmid = {25433524}, issn = {1471-2180}, support = {R01 GM018568/GM/NIGMS NIH HHS/United States ; R37 GM018568/GM/NIGMS NIH HHS/United States ; GM18568/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacillus subtilis/*genetics/*physiology ; Bacterial Proteins/*genetics/metabolism ; Biofilms/*growth & development ; *Gene Expression Regulation, Bacterial ; Mutant Proteins/genetics/metabolism ; Point Mutation ; }, abstract = {BACKGROUND: Bacteria often form multicellular, organized communities known as biofilms, which protect cells from a variety of environmental stresses. During biofilm formation, bacteria secrete a species-specific matrix; in Bacillus subtilis biofilms, the matrix consists of protein polymers and exopolysaccharide. Many domesticated strains of B. subtilis have a reduced ability to form biofilms, and we conducted a two-month evolution experiment to test whether laboratory culturing provides selective pressure against biofilm formation in B. subtilis.

RESULTS: Bacteria grown in two-month-long batch culture rapidly diversified their biofilm-forming characteristics, exhibiting highly diverse colony morphologies on LB plates in the initial ten days of culture. Generally, this diversity decreased over time; however, multiple types of colony morphology remained in our final two-month-old populations, both under shaking and static conditions. Notably, while our final populations featured cells that produce less biofilm matrix than did the ancestor, cells overproducing biofilm matrix were present as well. We took a candidate-gene approach to identify mutations in the strains that overproduced matrix and found point mutations in the biofilm-regulatory gene sinR. Introducing these mutations into the ancestral strain phenocopied or partially phenocopied the evolved biofilm phenotypes.

CONCLUSIONS: Our data suggest that standard laboratory culturing conditions do not rapidly select against biofilm formation. Although biofilm matrix production is often reduced in domesticated bacterial strains, we found that matrix production may still have a fitness benefit in the laboratory. We suggest that adaptive specialization of biofilm-forming species can occur through mutations that modulate biofilm formation as in B. subtilis.}, } @article {pmid25432513, year = {2014}, author = {Govindasamy, N and Murthy, S and Ghanekar, Y}, title = {Slow-cycling stem cells in hydra contribute to head regeneration.}, journal = {Biology open}, volume = {3}, number = {12}, pages = {1236-1244}, pmid = {25432513}, issn = {2046-6390}, abstract = {Adult stem cells face the challenge of maintaining tissue homeostasis by self-renewal while maintaining their proliferation potential over the lifetime of an organism. Continuous proliferation can cause genotoxic/metabolic stress that can compromise the genomic integrity of stem cells. To prevent stem cell exhaustion, highly proliferative adult tissues maintain a pool of quiescent stem cells that divide only in response to injury and thus remain protected from genotoxic stress. Hydra is a remarkable organism with highly proliferative stem cells and ability to regenerate at whole animal level. Intriguingly, hydra does not display consequences of high proliferation, such as senescence or tumour formation. In this study, we investigate if hydra harbours a pool of slow-cycling stem cells that could help prevent undesirable consequences of continuous proliferation. Hydra were pulsed with the thymidine analogue 5-ethynyl-2'-deoxyuridine (EdU) and then chased in the absence of EdU to monitor the presence of EdU-retaining cells. A significant number of undifferentiated cells of all three lineages in hydra retained EdU for about 8-10 cell cycles, indicating that these cells did not enter cell cycle. These label-retaining cells were resistant to hydroxyurea treatment and were predominantly in the G2 phase of cell cycle. Most significantly, similar to mammalian quiescent stem cells, these cells rapidly entered cell division during head regeneration. This study shows for the first time that, contrary to current beliefs, cells in hydra display heterogeneity in their cell cycle potential and the slow-cycling cells in this population enter cell cycle during head regeneration. These results suggest an early evolution of slow-cycling stem cells in multicellular animals.}, } @article {pmid25427284, year = {2014}, author = {Sciumè, G and Santagiuliana, R and Ferrari, M and Decuzzi, P and Schrefler, BA}, title = {A tumor growth model with deformable ECM.}, journal = {Physical biology}, volume = {11}, number = {6}, pages = {065004}, pmid = {25427284}, issn = {1478-3975}, support = {U54 CA143837/CA/NCI NIH HHS/United States ; U54 CA151668/CA/NCI NIH HHS/United States ; U54CA143837/CA/NCI NIH HHS/United States ; U54CA151668/CA/NCI NIH HHS/United States ; }, mesh = {Biomechanical Phenomena ; Computational Biology/*methods ; Extracellular Matrix/metabolism/*pathology ; Humans ; Melanoma/metabolism/*pathology ; *Models, Biological ; Oxygen/metabolism ; Porosity ; Skin Neoplasms/*pathology ; Spheroids, Cellular/metabolism/pathology ; Tumor Cells, Cultured ; }, abstract = {Existing tumor growth models based on fluid analogy for the cells do not generally include the extracellular matrix (ECM), or if present, take it as rigid. The three-fluid model originally proposed by the authors and comprising tumor cells (TC), host cells (HC), interstitial fluid (IF) and an ECM, considered up to now only a rigid ECM in the applications. This limitation is here relaxed and the deformability of the ECM is investigated in detail. The ECM is modeled as a porous solid matrix with Green-elastic and elasto-visco-plastic material behavior within a large strain approach. Jauman and Truesdell objective stress measures are adopted together with the deformation rate tensor. Numerical results are first compared with those of a reference experiment of a multicellular tumor spheroid (MTS) growing in vitro, then three different tumor cases are studied: growth of an MTS in a decellularized ECM, growth of a spheroid in the presence of host cells and growth of a melanoma. The influence of the stiffness of the ECM is evidenced and comparison with the case of a rigid ECM is made. The processes in a deformable ECM are more rapid than in a rigid ECM and the obtained growth pattern differs. The reasons for this are due to the changes in porosity induced by the tumor growth. These changes are inhibited in a rigid ECM. This enhanced computational model emphasizes the importance of properly characterizing the biomechanical behavior of the malignant mass in all its components to correctly predict its temporal and spatial pattern evolution.}, } @article {pmid25400313, year = {2014}, author = {Espinosa, A and Paz-Y-Miño-C, G}, title = {Evidence of Taxa-, Clone-, and Kin-discrimination in Protists: Ecological and Evolutionary Implications.}, journal = {Evolutionary ecology}, volume = {28}, number = {6}, pages = {1019-1029}, pmid = {25400313}, issn = {0269-7653}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; }, abstract = {Unicellular eukaryotes, or protists, are among the most ancient organisms on Earth. Protists belong to multiple taxonomic groups; they are widely distributed geographically and in all environments. Their ability to discriminate among con- and heterospecifics has been documented during the past decade. Here we discuss exemplar cases of taxa-, clone-, and possible kin-discrimination in five major lineages: Mycetozoa (Dictyostelium, Polysphondylium), Dikarya (Saccharomyces), Ciliophora (Tetrahymena), Apicomplexa (Plasmodium) and Archamoebae (Entamoeba). We summarize the proposed genetic mechanisms involved in discrimination-mediated aggregation (self versus different), including the csA, FLO and trg (formerly lag) genes, and the Proliferation Activation Factors (PAFs), which facilitate clustering in some protistan taxa. We caution about the experimental challenges intrinsic to studying recognition in protists, and highlight the opportunities for exploring the ecology and evolution of complex forms of cell-cell communication, including social behavior, in a polyphyletic, still superficially understood group of organisms. Because unicellular eukaryotes are the evolutionary precursors of multicellular life, we infer that their mechanisms of taxa-, clone-, and possible kin-discrimination gave origin to the complex diversification and sophistication of traits associated with species and kin recognition in plants, fungi, invertebrates and vertebrates.}, } @article {pmid25395670, year = {2014}, author = {Murray, PS and Zaidel-Bar, R}, title = {Pre-metazoan origins and evolution of the cadherin adhesome.}, journal = {Biology open}, volume = {3}, number = {12}, pages = {1183-1195}, pmid = {25395670}, issn = {2046-6390}, abstract = {Vertebrate adherens junctions mediate cell-cell adhesion via a "classical" cadherin-catenin "core" complex, which is associated with and regulated by a functional network of proteins, collectively named the cadherin adhesome ("cadhesome"). The most basal metazoans have been shown to conserve the cadherin-catenin "core", but little is known about the evolution of the cadhesome. Using a bioinformatics approach based on both sequence and structural analysis, we have traced the evolution of this larger network in 26 organisms, from the uni-cellular ancestors of metazoans, through basal metazoans, to vertebrates. Surprisingly, we show that approximately 70% of the cadhesome, including proteins with similarity to the catenins, predate metazoans. We found that the transition to multicellularity was accompanied by the appearance of a small number of adaptor proteins, and we show how these proteins may have helped to integrate pre-metazoan sub-networks via PDZ domain-peptide interactions. Finally, we found the increase in network complexity in higher metazoans to have been driven primarily by expansion of paralogs. In summary, our analysis helps to explain how the complex protein network associated with cadherin at adherens junctions first came together in the first metazoan and how it evolved into the even more complex mammalian cadhesome.}, } @article {pmid25395297, year = {2014}, author = {Kagan, JC and Barton, GM}, title = {Emerging principles governing signal transduction by pattern-recognition receptors.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {7}, number = {3}, pages = {a016253}, pmid = {25395297}, issn = {1943-0264}, support = {R01 AI093589/AI/NIAID NIH HHS/United States ; AI072955/AI/NIAID NIH HHS/United States ; R01 AI095587/AI/NIAID NIH HHS/United States ; P30DK34854/DK/NIDDK NIH HHS/United States ; AI095587/AI/NIAID NIH HHS/United States ; R01 AI104914/AI/NIAID NIH HHS/United States ; R56 AI095587/AI/NIAID NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; AI072429/AI/NIAID NIH HHS/United States ; K99 AI072955/AI/NIAID NIH HHS/United States ; AI104914/AI/NIAID NIH HHS/United States ; AI063302/AI/NIAID NIH HHS/United States ; P01 AI063302/AI/NIAID NIH HHS/United States ; R01 AI072429/AI/NIAID NIH HHS/United States ; AI093589/AI/NIAID NIH HHS/United States ; R00 AI072955/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; Immunity, Innate/*physiology ; *Models, Immunological ; Nucleic Acids/metabolism ; Plakins/*metabolism ; Receptors, Cytoplasmic and Nuclear/*metabolism ; Signal Transduction/*immunology ; Toll-Like Receptors/*metabolism ; }, abstract = {The problem of recognizing and disposing of non-self-organisms, whether for nutrients or defense, predates the evolution of multicellularity. Accordingly, the function of the innate immune system is often intimately associated with fundamental aspects of cell biology. Here, we review our current understanding of the links between cell biology and pattern-recognition receptors of the innate immune system. We highlight the importance of receptor localization for the detection of microbes and for the initiation of antimicrobial signaling pathways. We discuss examples that illustrate how pattern-recognition receptors influence, and are influenced by, the general membrane trafficking machinery of mammalian cells. In the future, cell biological analysis likely will rival pure genetic analysis as a tool to uncover fundamental principles that govern host-microbe interactions.}, } @article {pmid25392735, year = {2014}, author = {Chen, PY and Montanini, B and Liao, WW and Morselli, M and Jaroszewicz, A and Lopez, D and Ottonello, S and Pellegrini, M}, title = {A comprehensive resource of genomic, epigenomic and transcriptomic sequencing data for the black truffle Tuber melanosporum.}, journal = {GigaScience}, volume = {3}, number = {}, pages = {25}, pmid = {25392735}, issn = {2047-217X}, support = {T32 HG002536/HG/NHGRI NIH HHS/United States ; }, abstract = {BACKGROUND: Tuber melanosporum, also known in the gastronomic community as "truffle", features one of the largest fungal genomes (125 Mb) with an exceptionally high transposable element (TE) and repetitive DNA content (>58%). The main purpose of DNA methylation in fungi is TE silencing. As obligate outcrossing organisms, truffles are bound to a sexual mode of propagation, which together with TEs is thought to represent a major force driving the evolution of DNA methylation. Thus, it was of interest to examine if and how T. melanosporum exploits DNA methylation to maintain genome integrity.

FINDINGS: We performed whole-genome DNA bisulfite sequencing and mRNA sequencing on different developmental stages of T. melanosporum; namely, fruitbody ("truffle"), free-living mycelium and ectomycorrhiza. The data revealed a high rate of cytosine methylation (>44%), selectively targeting TEs rather than genes with a strong preference for CpG sites. Whole genome DNA sequencing uncovered multiple TE-enriched, copy number variant regions bearing a significant fraction of hypomethylated and expressed TEs, almost exclusively in free-living mycelium propagated in vitro. Treatment of mycelia with 5-azacytidine partially reduced DNA methylation and increased TE transcription. Our transcriptome assembly also resulted in the identification of a set of novel transcripts from 614 genes.

CONCLUSIONS: The datasets presented here provide valuable and comprehensive (epi)genomic information that can be of interest for evolutionary genomics studies of multicellular (filamentous) fungi, in particular Ascomycetes belonging to the subphylum, Pezizomycotina. Evidence derived from comparative methylome and transcriptome analyses indicates that a non-exhaustive and partly reversible methylation process operates in truffles.}, } @article {pmid25383925, year = {2014}, author = {Wildenberg, GA and Murray, AW}, title = {Evolving a 24-hr oscillator in budding yeast.}, journal = {eLife}, volume = {3}, number = {}, pages = {}, pmid = {25383925}, issn = {2050-084X}, support = {F32 GM085920/GM/NIGMS NIH HHS/United States ; P50 GM068763/GM/NIGMS NIH HHS/United States ; }, abstract = {We asked how a new, complex trait evolves by selecting for diurnal oscillations in the budding yeast, Saccharomyces cerevisiae. We expressed yellow fluorescent protein (YFP) from a yeast promoter and selected for a regular alternation between low and high fluorescence over a 24-hr period. This selection produced changes in cell adhesion rather than YFP expression: clonal populations oscillated between single cells and multicellular clumps. The oscillations are not a response to environmental cues and continue for at least three cycles in a constant environment. We identified eight putative causative mutations in one clone and recreated the evolved phenotype in the ancestral strain. The mutated genes lack obvious relationships to each other, but multiple lineages change from the haploid to the diploid pattern of gene expression. We show that a novel, complex phenotype can evolve by small sets of mutations in genes whose molecular functions appear to be unrelated to each other.}, } @article {pmid25375671, year = {2014}, author = {Buitrago-Flórez, FJ and Restrepo, S and Riaño-Pachón, DM}, title = {Identification of transcription factor genes and their correlation with the high diversity of stramenopiles.}, journal = {PloS one}, volume = {9}, number = {11}, pages = {e111841}, pmid = {25375671}, issn = {1932-6203}, mesh = {Animals ; Biodiversity ; Evolution, Molecular ; Gene Expression Regulation ; Genome ; Multigene Family ; Phylogeny ; Stramenopiles/*classification/*genetics ; Transcription Factors/*genetics ; }, abstract = {The biological diversity among Stramenopiles is striking; they range from large multicellular seaweeds to tiny unicellular species, they embrace many ecologically important autothrophic (e.g., diatoms, brown algae), and heterotrophic (e.g., oomycetes) groups. Transcription factors (TFs) and other transcription regulators (TRs) regulate spatial and temporal gene expression. A plethora of transcriptional regulatory proteins have been identified and classified into families on the basis of sequence similarity. The purpose of this work is to identify the TF and TR complement in diverse species belonging to Stramenopiles in order to understand how these regulators may contribute to their observed diversity. We identified and classified 63 TF and TR families in 11 species of Stramenopiles. In some species we found gene families with high relative importance. Taking into account the 63 TF and TR families identified, 28 TF and TR families were established to be positively correlated with specific traits like number of predicted proteins, number of flagella and number of cell types during the life cycle. Additionally, we found gains and losses in TF and TR families specific to some species and clades, as well as, two families with high abundance specific to the autotrophic species and three families with high abundance specific to the heterotropic species. For the first time, there is a systematic search of TF and TR families in Stramenopiles. The attempts to uncover relationships between these families and the complexity of this group may be of great impact, considering that there are several important pathogens of plants and animals, as well as, important species involved in carbon cycling. Specific TF and TR families identified in this work appear to be correlated with particular traits in the Stramenopiles group and may be correlated with the high complexity and diversity in Stramenopiles.}, } @article {pmid25374544, year = {2014}, author = {Kowalski, WJ and Pekkan, K and Tinney, JP and Keller, BB}, title = {Investigating developmental cardiovascular biomechanics and the origins of congenital heart defects.}, journal = {Frontiers in physiology}, volume = {5}, number = {}, pages = {408}, pmid = {25374544}, issn = {1664-042X}, abstract = {Innovative research on the interactions between biomechanical load and cardiovascular (CV) morphogenesis by multiple investigators over the past 3 decades, including the application of bioengineering approaches, has shown that the embryonic heart adapts both structure and function in order to maintain cardiac output to the rapidly growing embryo. Acute adaptive hemodynamic mechanisms in the embryo include the redistribution of blood flow within the heart, dynamic adjustments in heart rate and developed pressure, and beat to beat variations in blood flow and vascular resistance. These biomechanically relevant events occur coincident with adaptive changes in gene expression and trigger adaptive mechanisms that include alterations in myocardial cell growth and death, regional and global changes in myocardial architecture, and alterations in central vascular morphogenesis and remodeling. These adaptive mechanisms allow the embryo to survive these biomechanical stresses (environmental, maternal) and to compensate for developmental errors (genetic). Recent work from numerous laboratories shows that a subset of these adaptive mechanisms is present in every developing multicellular organism with a "heart" equivalent structure. This chapter will provide the reader with an overview of some of the approaches used to quantify embryonic CV functional maturation and performance, provide several illustrations of experimental interventions that explore the role of biomechanics in the regulation of CV morphogenesis including the role of computational modeling, and identify several critical areas for future investigation as available experimental models and methods expand.}, } @article {pmid25373677, year = {2014}, author = {Hammerschmidt, K and Rose, CJ and Kerr, B and Rainey, PB}, title = {Life cycles, fitness decoupling and the evolution of multicellularity.}, journal = {Nature}, volume = {515}, number = {7525}, pages = {75-79}, pmid = {25373677}, issn = {1476-4687}, mesh = {*Biological Evolution ; *Cell Physiological Phenomena ; *Genetic Fitness ; *Life Cycle Stages ; *Models, Biological ; Phenotype ; Pseudomonas fluorescens/*cytology/growth & development/*physiology ; }, abstract = {Cooperation is central to the emergence of multicellular life; however, the means by which the earliest collectives (groups of cells) maintained integrity in the face of destructive cheating types is unclear. One idea posits cheats as a primitive germ line in a life cycle that facilitates collective reproduction. Here we describe an experiment in which simple cooperating lineages of bacteria were propagated under a selective regime that rewarded collective-level persistence. Collectives reproduced via life cycles that either embraced, or purged, cheating types. When embraced, the life cycle alternated between phenotypic states. Selection fostered inception of a developmental switch that underpinned the emergence of collectives whose fitness, during the course of evolution, became decoupled from the fitness of constituent cells. Such development and decoupling did not occur when groups reproduced via a cheat-purging regime. Our findings capture key events in the evolution of Darwinian individuality during the transition from single cells to multicellularity.}, } @article {pmid25371433, year = {2015}, author = {Frank, MH and Scanlon, MJ}, title = {Transcriptomic evidence for the evolution of shoot meristem function in sporophyte-dominant land plants through concerted selection of ancestral gametophytic and sporophytic genetic programs.}, journal = {Molecular biology and evolution}, volume = {32}, number = {2}, pages = {355-367}, doi = {10.1093/molbev/msu303}, pmid = {25371433}, issn = {1537-1719}, mesh = {Biological Evolution ; Bryopsida/classification/metabolism ; Evolution, Molecular ; Gene Expression Regulation, Plant ; Germ Cells, Plant/classification/*metabolism ; Meristem/genetics/*metabolism ; Plant Proteins/genetics ; }, abstract = {Alternation of generations, in which the haploid and diploid stages of the life cycle are each represented by multicellular forms that differ in their morphology, is a defining feature of the land plants (embryophytes). Anciently derived lineages of embryophytes grow predominately in the haploid gametophytic generation from apical cells that give rise to the photosynthetic body of the plant. More recently evolved plant lineages have multicellular shoot apical meristems (SAMs), and photosynthetic shoot development is restricted to the sporophyte generation. The molecular genetic basis for this evolutionary shift from gametophyte-dominant to sporophyte-dominant life cycles remains a major question in the study of land plant evolution. We used laser microdissection and next generation RNA sequencing to address whether angiosperm meristem patterning genes expressed in the sporophytic SAM of Zea mays are expressed in the gametophytic apical cells, or in the determinate sporophytes, of the model bryophytes Marchantia polymorpha and Physcomitrella patens. A wealth of upregulated genes involved in stem cell maintenance and organogenesis are identified in the maize SAM and in both the gametophytic apical cell and sporophyte of moss, but not in Marchantia. Significantly, meiosis-specific genetic programs are expressed in bryophyte sporophytes, long before the onset of sporogenesis. Our data suggest that this upregulated accumulation of meiotic gene transcripts suppresses indeterminate cell fate in the Physcomitrella sporophyte, and overrides the observed accumulation of meristem patterning genes. A model for the evolution of indeterminate growth in the sporophytic generation through the concerted selection of ancestral meristem gene programs from gametophyte-dominant lineages is proposed.}, } @article {pmid25369637, year = {2014}, author = {de Mendoza, A and Ruiz-Trillo, I}, title = {Forward genetics for back-in-time questions.}, journal = {eLife}, volume = {3}, number = {}, pages = {}, pmid = {25369637}, issn = {2050-084X}, mesh = {Animals ; Choanoflagellata/*genetics/growth & development ; *Genetics ; Lectins, C-Type/metabolism ; Life Cycle Stages ; Mutation/genetics ; }, abstract = {A genetic screen has revealed one of the molecules that allow choanoflagellates, the closest unicellular relative of animals, to form colonies, which could help researchers to answer questions about the earliest days of animal evolution.}, } @article {pmid25360248, year = {2014}, author = {Diaz, SA and Viney, M}, title = {Genotypic-specific variance in Caenorhabditis elegans lifetime fecundity.}, journal = {Ecology and evolution}, volume = {4}, number = {11}, pages = {2058-2069}, pmid = {25360248}, issn = {2045-7758}, abstract = {Organisms live in heterogeneous environments, so strategies that maximze fitness in such environments will evolve. Variation in traits is important because it is the raw material on which natural selection acts during evolution. Phenotypic variation is usually thought to be due to genetic variation and/or environmentally induced effects. Therefore, genetically identical individuals in a constant environment should have invariant traits. Clearly, genetically identical individuals do differ phenotypically, usually thought to be due to stochastic processes. It is now becoming clear, especially from studies of unicellular species, that phenotypic variance among genetically identical individuals in a constant environment can be genetically controlled and that therefore, in principle, this can be subject to selection. However, there has been little investigation of these phenomena in multicellular species. Here, we have studied the mean lifetime fecundity (thus a trait likely to be relevant to reproductive success), and variance in lifetime fecundity, in recently-wild isolates of the model nematode Caenorhabditis elegans. We found that these genotypes differed in their variance in lifetime fecundity: some had high variance in fecundity, others very low variance. We find that this variance in lifetime fecundity was negatively related to the mean lifetime fecundity of the lines, and that the variance of the lines was positively correlated between environments. We suggest that the variance in lifetime fecundity may be a bet-hedging strategy used by this species.}, } @article {pmid25354656, year = {2015}, author = {Beech, RN and Neveu, C}, title = {The evolution of pentameric ligand-gated ion-channels and the changing family of anthelmintic drug targets.}, journal = {Parasitology}, volume = {142}, number = {2}, pages = {303-317}, doi = {10.1017/S003118201400170X}, pmid = {25354656}, issn = {1469-8161}, mesh = {Animals ; Anthelmintics/*pharmacology ; Helminths/*drug effects/genetics/*metabolism ; Ion Channel Gating/*physiology ; Ion Channels/genetics/*metabolism ; Phylogeny ; }, abstract = {SUMMARY Pentameric ligand-gated ion-channels rapidly transduce synaptic neurotransmitter signals to an electrical response in post-synaptic neuronal or muscle cells and control the neuromusculature of a majority of multicellular animals. A wide range of pharmaceuticals target these receptors including ethanol, nicotine, anti-depressants and other mood regulating drugs, compounds that control pain and mobility and are targeted by a majority of anthelmintic drugs used to control parasitic infection of humans and livestock. Major advances have been made in recent years to our understanding of the structure, function, activity and the profile of compounds that can activate specific receptors. It is becoming clear that these anthelmintic drug targets are not fixed, but differ in significant details from one nematode species to another. Here we review what is known about the evolution of the pentameric ligand-gated ion-channels, paying particular attention to the nematodes, how we can infer the origins of such receptors and understand the factors that determine how they change both over time and from one species to another. Using this knowledge provides a biological framework in which to understand these important drug targets and avenues to identify new receptors and aid the search for new anthelmintic drugs.}, } @article {pmid25349527, year = {2014}, author = {de Jong, Y and Verbeek, M and Michelsen, V and Bjørn, Pde P and Los, W and Steeman, F and Bailly, N and Basire, C and Chylarecki, P and Stloukal, E and Hagedorn, G and Wetzel, FT and Glöckler, F and Kroupa, A and Korb, G and Hoffmann, A and Häuser, C and Kohlbecker, A and Müller, A and Güntsch, A and Stoev, P and Penev, L}, title = {Fauna Europaea - all European animal species on the web.}, journal = {Biodiversity data journal}, volume = {}, number = {2}, pages = {e4034}, pmid = {25349527}, issn = {1314-2828}, abstract = {Fauna Europaea is Europe's main zoological taxonomic index, making the scientific names and distributions of all living, currently known, multicellular, European land and freshwater animals species integrally available in one authoritative database. Fauna Europaea covers about 260,000 taxon names, including 145,000 accepted (sub)species, assembled by a large network of (>400) leading specialists, using advanced electronic tools for data collations with data quality assured through sophisticated validation routines. Fauna Europaea started in 2000 as an EC funded FP5 project and provides a unique taxonomic reference for many user-groups such as scientists, governments, industries, nature conservation communities and educational programs. Fauna Europaea was formally accepted as an INSPIRE standard for Europe, as part of the European Taxonomic Backbone established in PESI. Fauna Europaea provides a public web portal at faunaeur.org with links to other key biodiversity services, is installed as a taxonomic backbone in wide range of biodiversity services and actively contributes to biodiversity informatics innovations in various initiatives and EC programs.}, } @article {pmid25345707, year = {2014}, author = {Felsenfeld, G}, title = {The evolution of epigenetics.}, journal = {Perspectives in biology and medicine}, volume = {57}, number = {1}, pages = {132-148}, doi = {10.1353/pbm.2014.0004}, pmid = {25345707}, issn = {1529-8795}, support = {//Intramural NIH HHS/United States ; }, mesh = {Chromatin/chemistry/genetics ; DNA Methylation ; *Epigenesis, Genetic ; *Evolution, Molecular ; Sequence Analysis, DNA ; }, abstract = {Early studies of the developing embryo raised the question of how a fertilized egg could give rise to a complex multicellular organism containing many different kinds of cells. The term epigenetics originally referred to the study of these processes. With the advent of detailed knowledge of mechanisms of gene expression, this definition was superseded by another: epigenetics concerned the transmission of phenotype through mitosis or the germ line by mechanisms that did not involve changes in the DNA sequence. Much effort has been spent in attempting to identify and characterize these events. Work initially focused on DNA methylation as an epigenetic mark, but more recently there has been an emphasis on histone modifications as possible carriers of epigenetic information. However, there is confusion between situations in which the modifications may be propagated through cell division, thus helping to maintain a pattern of gene expression, and situations in which the modifications are simply part of the transcriptional apparatus. Arguments about the role of the histones have led to a reexamination of the definition of epigenetics and the primary events in development leading to cell type specific gene expression patterns.}, } @article {pmid25342789, year = {2014}, author = {Libby, E and Ratcliff, WC}, title = {Evolution. Ratcheting the evolution of multicellularity.}, journal = {Science (New York, N.Y.)}, volume = {346}, number = {6208}, pages = {426-427}, doi = {10.1126/science.1262053}, pmid = {25342789}, issn = {1095-9203}, mesh = {Animals ; Apoptosis ; *Biological Evolution ; Cells/*cytology ; Life Cycle Stages ; }, } @article {pmid25329823, year = {2014}, author = {Lehr, NA and Wang, Z and Li, N and Hewitt, DA and López-Giráldez, F and Trail, F and Townsend, JP}, title = {Gene expression differences among three Neurospora species reveal genes required for sexual reproduction in Neurospora crassa.}, journal = {PloS one}, volume = {9}, number = {10}, pages = {e110398}, pmid = {25329823}, issn = {1932-6203}, support = {UL1 TR000142/TR/NCATS NIH HHS/United States ; }, mesh = {Cinnamates/pharmacology ; Drug Resistance, Fungal/genetics ; Fruiting Bodies, Fungal/genetics ; Fungal Proteins/biosynthesis/genetics/metabolism ; *Gene Expression Regulation, Fungal/drug effects ; Gene Knockout Techniques ; Hygromycin B/analogs & derivatives/pharmacology ; Mutation ; Neurospora crassa/drug effects/*genetics/metabolism/*physiology ; Phenotype ; Protein Transport ; Reproduction/drug effects/genetics ; Species Specificity ; Time Factors ; Transcription, Genetic/drug effects ; }, abstract = {Many fungi form complex three-dimensional fruiting bodies, within which the meiotic machinery for sexual spore production has been considered to be largely conserved over evolutionary time. Indeed, much of what we know about meiosis in plant and animal taxa has been deeply informed by studies of meiosis in Saccharomyces and Neurospora. Nevertheless, the genetic basis of fruiting body development and its regulation in relation to meiosis in fungi is barely known, even within the best studied multicellular fungal model Neurospora crassa. We characterized morphological development and genome-wide transcriptomics in the closely related species Neurospora crassa, Neurospora tetrasperma, and Neurospora discreta, across eight stages of sexual development. Despite diverse life histories within the genus, all three species produce vase-shaped perithecia. Transcriptome sequencing provided gene expression levels of orthologous genes among all three species. Expression of key meiosis genes and sporulation genes corresponded to known phenotypic and developmental differences among these Neurospora species during sexual development. We assembled a list of genes putatively relevant to the recent evolution of fruiting body development by sorting genes whose relative expression across developmental stages increased more in N. crassa relative to the other species. Then, in N. crassa, we characterized the phenotypes of fruiting bodies arising from crosses of homozygous knockout strains of the top genes. Eight N. crassa genes were found to be critical for the successful formation of perithecia. The absence of these genes in these crosses resulted in either no perithecium formation or in arrested development at an early stage. Our results provide insight into the genetic basis of Neurospora sexual reproduction, which is also of great importance with regard to other multicellular ascomycetes, including perithecium-forming pathogens, such as Claviceps purpurea, Ophiostoma ulmi, and Glomerella graminicola.}, } @article {pmid25328099, year = {2015}, author = {Dzutsev, A and Goldszmid, RS and Viaud, S and Zitvogel, L and Trinchieri, G}, title = {The role of the microbiota in inflammation, carcinogenesis, and cancer therapy.}, journal = {European journal of immunology}, volume = {45}, number = {1}, pages = {17-31}, doi = {10.1002/eji.201444972}, pmid = {25328099}, issn = {1521-4141}, support = {HHSN26120080001E//PHS HHS/United States ; //Intramural NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Animals ; Antineoplastic Agents/therapeutic use ; Autoimmune Diseases/drug therapy/*microbiology/pathology ; Biological Evolution ; Carcinogenesis/*immunology/pathology ; Humans ; Immunity, Innate ; Immunomodulation ; Inflammation/drug therapy/immunology/microbiology/pathology ; Metagenome/immunology ; Mice ; Microbiota/*immunology ; Neoplasms/drug therapy/immunology/*microbiology/pathology ; Symbiosis/immunology ; Tumor Escape ; }, abstract = {Commensal microorganisms colonize barrier surfaces of all multicellular organisms, including those of humans. For more than 500 million years, commensal microorganisms and their hosts have coevolved and adapted to each other. As a result, the commensal microbiota affects many immune and nonimmune functions of their hosts, and de facto the two together comprise one metaorganism. The commensal microbiota communicates with the host via biologically active molecules. Recently, it has been reported that microbial imbalance may play a critical role in the development of multiple diseases, such as cancer, autoimmune conditions, and increased susceptibility to infection. In this review, we focus on the role of the commensal microbiota in the development, progression, and immune evasion of cancer, as well as some modulatory effects on the treatment of cancer. In particular, we discuss the mechanisms of microbiota-mediated regulation of innate and adaptive immune responses to tumors, and the consequences on cancer progression and whether tumors subsequently become resistant or susceptible to different anticancer therapeutic regiments.}, } @article {pmid25324214, year = {2014}, author = {Umen, JG}, title = {Green algae and the origins of multicellularity in the plant kingdom.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {6}, number = {11}, pages = {a016170}, pmid = {25324214}, issn = {1943-0264}, support = {R01 GM078376/GM/NIGMS NIH HHS/United States ; R01 GM092744/GM/NIGMS NIH HHS/United States ; R01GM092744/GM/NIGMS NIH HHS/United States ; R01GM078376/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Cell Differentiation ; Chlorophyta/*cytology/genetics/growth & development ; Phylogeny ; Plant Cells/physiology ; Plants/anatomy & histology/genetics ; Reproduction ; }, abstract = {The green lineage of chlorophyte algae and streptophytes form a large and diverse clade with multiple independent transitions to produce multicellular and/or macroscopically complex organization. In this review, I focus on two of the best-studied multicellular groups of green algae: charophytes and volvocines. Charophyte algae are the closest relatives of land plants and encompass the transition from unicellularity to simple multicellularity. Many of the innovations present in land plants have their roots in the cell and developmental biology of charophyte algae. Volvocine algae evolved an independent route to multicellularity that is captured by a graded series of increasing cell-type specialization and developmental complexity. The study of volvocine algae has provided unprecedented insights into the innovations required to achieve multicellularity.}, } @article {pmid25315413, year = {2014}, author = {Laporte, D and Huot, JL and Bader, G and Enkler, L and Senger, B and Becker, HD}, title = {Exploring the evolutionary diversity and assembly modes of multi-aminoacyl-tRNA synthetase complexes: lessons from unicellular organisms.}, journal = {FEBS letters}, volume = {588}, number = {23}, pages = {4268-4278}, doi = {10.1016/j.febslet.2014.10.007}, pmid = {25315413}, issn = {1873-3468}, mesh = {Amino Acyl-tRNA Synthetases/*chemistry/*metabolism ; Animals ; *Evolution, Molecular ; Humans ; *Protein Structure, Quaternary ; Protein Structure, Tertiary ; Species Specificity ; }, abstract = {Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous and ancient enzymes, mostly known for their essential role in generating aminoacylated tRNAs. During the last two decades, many aaRSs have been found to perform additional and equally crucial tasks outside translation. In metazoans, aaRSs have been shown to assemble, together with non-enzymatic assembly proteins called aaRSs-interacting multifunctional proteins (AIMPs), into so-called multi-synthetase complexes (MSCs). Metazoan MSCs are dynamic particles able to specifically release some of their constituents in response to a given stimulus. Upon their release from MSCs, aaRSs can reach other subcellular compartments, where they often participate to cellular processes that do not exploit their primary function of synthesizing aminoacyl-tRNAs. The dynamics of MSCs and the expansion of the aaRSs functional repertoire are features that are so far thought to be restricted to higher and multicellular eukaryotes. However, much can be learnt about how MSCs are assembled and function from apparently 'simple' organisms. Here we provide an overview on the diversity of these MSCs, their composition, mode of assembly and the functions that their constituents, namely aaRSs and AIMPs, exert in unicellular organisms.}, } @article {pmid25309731, year = {2014}, author = {Dubravcic, D and van Baalen, M and Nizak, C}, title = {An evolutionarily significant unicellular strategy in response to starvation in Dictyostelium social amoebae.}, journal = {F1000Research}, volume = {3}, number = {}, pages = {133}, pmid = {25309731}, issn = {2046-1402}, abstract = {The social amoeba Dictyostelium discoideum is widely studied for its multicellular development program as a response to starvation. Aggregates of up to 10 (6) cells form fruiting bodies containing (i) dormant spores (~80%) that can persist for months in the absence of nutrients, and (ii) dead stalk cells (~20%) that promote the dispersion of the spores towards nutrient-rich areas. It is often overlooked that not all cells aggregate upon starvation. Using a new quantitative approach based on time-lapse fluorescence microscopy and a low ratio of reporting cells, we have quantified this fraction of non-aggregating cells. In realistic starvation conditions, up to 15% of cells do not aggregate, which makes this third cell fate a significant component of the population-level response of social amoebae to starvation. Non-aggregating cells have an advantage over cells in aggregates since they resume growth earlier upon arrival of new nutrients, but have a shorter lifespan under prolonged starvation. We find that phenotypic heterogeneities linked to cell nutritional state bias the representation of cells in the aggregating vs. non-aggregating fractions, and thus affect population partitioning. Next, we report that the fraction of non-aggregating cells depends on genetic factors that regulate the timing of starvation, signal sensing efficiency and aggregation efficiency. In addition, interactions between clones in mixtures of non-isogenic cells affect the partitioning of each clone into both fractions. We further build a numerical model to test the evolutionary significance of the non-aggregating cell fraction. The partitioning of cells into aggregating and non-aggregating fractions is optimal in fluctuating environments with an unpredictable duration of starvation periods. Our study highlights the unicellular component of the response of social amoebae to starvation, and thus extends its evolutionary and ecological framework.}, } @article {pmid25309530, year = {2014}, author = {Garcia, JR and Gerardo, NM}, title = {The symbiont side of symbiosis: do microbes really benefit?.}, journal = {Frontiers in microbiology}, volume = {5}, number = {}, pages = {510}, pmid = {25309530}, issn = {1664-302X}, abstract = {Microbial associations are integral to all eukaryotes. Mutualism, the interaction of two species for the benefit of both, is an important aspect of microbial associations, with evidence that multicellular organisms in particular benefit from microbes. However, the microbe's perspective has largely been ignored, and it is unknown whether most microbial symbionts benefit from their associations with hosts. It has been presumed that microbial symbionts receive host-derived nutrients or a competition-free environment with reduced predation, but there have been few empirical tests, or even critical assessments, of these assumptions. We evaluate these hypotheses based on available evidence, which indicate reduced competition and predation are not universal benefits for symbionts. Some symbionts do receive nutrients from their host, but this has not always been linked to a corresponding increase in symbiont fitness. We recommend experiments to test symbiont fitness using current experimental systems of symbiosis and detail considerations for other systems. Incorporating symbiont fitness into symbiosis research will provide insight into the evolution of mutualistic interactions and cooperation in general.}, } @article {pmid25307499, year = {2015}, author = {Dunker, AK and Bondos, SE and Huang, F and Oldfield, CJ}, title = {Intrinsically disordered proteins and multicellular organisms.}, journal = {Seminars in cell & developmental biology}, volume = {37}, number = {}, pages = {44-55}, doi = {10.1016/j.semcdb.2014.09.025}, pmid = {25307499}, issn = {1096-3634}, mesh = {*Biological Evolution ; Eukaryotic Cells/chemistry/cytology/*metabolism ; Intrinsically Disordered Proteins/*chemistry/genetics/*metabolism ; Prokaryotic Cells/chemistry/cytology/*metabolism ; Protein Folding ; Protein Processing, Post-Translational ; }, abstract = {Intrinsically disordered proteins (IDPs) and IDP regions lack stable tertiary structure yet carry out numerous biological functions, especially those associated with signaling, transcription regulation, DNA condensation, cell division, and cellular differentiation. Both post-translational modifications (PTMs) and alternative splicing (AS) expand the functional repertoire of IDPs. Here we propose that an "IDP-based developmental toolkit," which is comprised of IDP regions, PTMs, especially multiple PTMs, within these IDP regions, and AS events within segments of pre-mRNA that code for these same IDP regions, allows functional diversification and environmental responsiveness for molecules that direct the development of complex metazoans.}, } @article {pmid25305337, year = {2014}, author = {Czárán, T and Hoekstra, RF and Aanen, DK}, title = {Selection against somatic parasitism can maintain allorecognition in fungi.}, journal = {Fungal genetics and biology : FG & B}, volume = {73}, number = {}, pages = {128-137}, doi = {10.1016/j.fgb.2014.09.010}, pmid = {25305337}, issn = {1096-0937}, mesh = {Animals ; Ascomycota ; *Biological Evolution ; Models, Biological ; Parasites/*genetics/metabolism ; Symbiosis/*genetics ; }, abstract = {Fusion between multicellular individuals is possible in many organisms with modular, indeterminate growth, such as marine invertebrates and fungi. Although fusion may provide various benefits, fusion usually is restricted to close relatives by allorecognition, also called heterokaryon or somatic incompatibility in fungi. A possible selective explanation for allorecognition is protection against somatic parasites. Such mutants contribute less to colony functions but more to reproduction. However, previous models testing this idea have failed to explain the high diversity of allorecognition alleles in nature. These models did not, however, consider the possible role of spatial structure. We model the joint evolution of allorecognition and somatic parasitism in a multicellular organism resembling an asexual ascomycete fungus in a spatially explicit simulation. In a 1000-by-1000 grid, neighbouring individuals can fuse, but only if they have the same allotype. Fusion with a parasitic individual decreases the total reproductive output of the fused individuals, but the parasite compensates for this individual-level fitness reduction by a disproportional share of the offspring. Allorecognition prevents the invasion of somatic parasites, and vice versa, mutation towards somatic parasitism provides the selective conditions for extensive allorecognition diversity. On the one hand, if allorecognition diversity did not build up fast enough, somatic parasites went to fixation; conversely, once parasites had gone to fixation no allorecognition diversity built up. On the other hand, the mere threat of parasitism could select for high allorecognition diversity, preventing invasion of somatic parasites. Moderate population viscosity combined with weak global dispersal was optimal for the joint evolution of allorecognition and protection against parasitism. Our results are consistent with the widespread occurrence of allorecognition in fungi and the low degree of somatic parasitism. We discuss the implications of our results for allorecognition in other organism groups.}, } @article {pmid25299705, year = {2014}, author = {Rodríguez-Rojas, A and Makarova, O and Rolff, J}, title = {Antimicrobials, stress and mutagenesis.}, journal = {PLoS pathogens}, volume = {10}, number = {10}, pages = {e1004445}, pmid = {25299705}, issn = {1553-7374}, mesh = {Animals ; Anti-Infective Agents/immunology/*pharmacology ; Antimicrobial Cationic Peptides/immunology/*pharmacology ; Bacteria/immunology ; Immunity, Innate/immunology ; Mutagenesis/*immunology ; Vertebrates/*immunology ; }, abstract = {Cationic antimicrobial peptides are ancient and ubiquitous immune effectors that multicellular organisms use to kill and police microbes whereas antibiotics are mostly employed by microorganisms. As antimicrobial peptides (AMPs) mostly target the cell wall, a microbial 'Achilles heel', it has been proposed that bacterial resistance evolution is very unlikely and hence AMPs are ancient 'weapons' of multicellular organisms. Here we provide a new hypothesis to explain the widespread distribution of AMPs amongst multicellular organism. Studying five antimicrobial peptides from vertebrates and insects, we show, using a classic Luria-Delbrück fluctuation assay, that cationic antimicrobial peptides (AMPs) do not increase bacterial mutation rates. Moreover, using rtPCR and disc diffusion assays we find that AMPs do not elicit SOS or rpoS bacterial stress pathways. This is in contrast to the main classes of antibiotics that elevate mutagenesis via eliciting the SOS and rpoS pathways. The notion of the 'Achilles heel' has been challenged by experimental selection for AMP-resistance, but our findings offer a new perspective on the evolutionary success of AMPs. Employing AMPs seems advantageous for multicellular organisms, as it does not fuel the adaptation of bacteria to their immune defenses. This has important consequences for our understanding of host-microbe interactions, the evolution of innate immune defenses, and also sheds new light on antimicrobial resistance evolution and the use of AMPs as drugs.}, } @article {pmid25299189, year = {2014}, author = {Levin, TC and Greaney, AJ and Wetzel, L and King, N}, title = {The Rosetteless gene controls development in the choanoflagellate S. rosetta.}, journal = {eLife}, volume = {3}, number = {}, pages = {}, pmid = {25299189}, issn = {2050-084X}, support = {R01 GM089977/GM/NIGMS NIH HHS/United States ; T32 GM007232/GM/NIGMS NIH HHS/United States ; GM089977/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Choanoflagellata/*genetics/*growth & development ; Gene Expression Regulation ; *Genes, Protozoan ; Lectins, C-Type/metabolism ; Models, Biological ; Molecular Sequence Data ; Mutation/genetics ; Phenotype ; Protozoan Proteins/chemistry/genetics/metabolism ; }, abstract = {The origin of animal multicellularity may be reconstructed by comparing animals with one of their closest living relatives, the choanoflagellate Salpingoeca rosetta. Just as animals develop from a single cell-the zygote-multicellular rosettes of S. rosetta develop from a founding cell. To investigate rosette development, we established forward genetics in S. rosetta. We find that the rosette defect of one mutant, named Rosetteless, maps to a predicted C-type lectin, a class of signaling and adhesion genes required for the development and innate immunity in animals. Rosetteless protein is essential for rosette development and forms an extracellular layer that coats and connects the basal poles of each cell in rosettes. This study provides the first link between genotype and phenotype in choanoflagellates and raises the possibility that a protein with C-type lectin-like domains regulated development in the last common ancestor of choanoflagellates and animals.}, } @article {pmid25295041, year = {2014}, author = {Buchmann, K}, title = {Evolution of Innate Immunity: Clues from Invertebrates via Fish to Mammals.}, journal = {Frontiers in immunology}, volume = {5}, number = {}, pages = {459}, pmid = {25295041}, issn = {1664-3224}, abstract = {Host responses against invading pathogens are basic physiological reactions of all living organisms. Since the appearance of the first eukaryotic cells, a series of defense mechanisms have evolved in order to secure cellular integrity, homeostasis, and survival of the host. Invertebrates, ranging from protozoans to metazoans, possess cellular receptors, which bind to foreign elements and differentiate self from non-self. This ability is in multicellular animals associated with presence of phagocytes, bearing different names (amebocytes, hemocytes, coelomocytes) in various groups including animal sponges, worms, cnidarians, mollusks, crustaceans, chelicerates, insects, and echinoderms (sea stars and urchins). Basically, these cells have a macrophage-like appearance and function and the repair and/or fight functions associated with these cells are prominent even at the earliest evolutionary stage. The cells possess pathogen recognition receptors recognizing pathogen-associated molecular patterns, which are well-conserved molecular structures expressed by various pathogens (virus, bacteria, fungi, protozoans, helminths). Scavenger receptors, Toll-like receptors, and Nod-like receptors (NLRs) are prominent representatives within this group of host receptors. Following receptor-ligand binding, signal transduction initiates a complex cascade of cellular reactions, which lead to production of one or more of a wide array of effector molecules. Cytokines take part in this orchestration of responses even in lower invertebrates, which eventually may result in elimination or inactivation of the intruder. Important innate effector molecules are oxygen and nitrogen species, antimicrobial peptides, lectins, fibrinogen-related peptides, leucine rich repeats (LRRs), pentraxins, and complement-related proteins. Echinoderms represent the most developed invertebrates and the bridge leading to the primitive chordates, cephalochordates, and urochordates, in which many autologous genes and functions from their ancestors can be found. They exhibit numerous variants of innate recognition and effector molecules, which allow fast and innate responses toward diverse pathogens despite lack of adaptive responses. The primitive vertebrates (agnathans also termed jawless fish) were the first to supplement innate responses with adaptive elements. Thus hagfish and lampreys use LRRs as variable lymphocyte receptors, whereas higher vertebrates [cartilaginous and bony fishes (jawed fish), amphibians, reptiles, birds, and mammals] developed the major histocompatibility complex, T-cell receptors, and B-cell receptors (immunoglobulins) as additional adaptive weaponry to assist innate responses. Extensive cytokine networks are recognized in fish, but related signal molecules can be traced among invertebrates. The high specificity, antibody maturation, immunological memory, and secondary responses of adaptive immunity were so successful that it allowed higher vertebrates to reduce the number of variants of the innate molecules originating from both invertebrates and lower vertebrates. Nonetheless, vertebrates combine the two arms in an intricate inter-dependent network. Organisms at all developmental stages have, in order to survive, applied available genes and functions of which some may have been lost or may have changed function through evolution. The molecular mechanisms involved in evolution of immune molecules, might apart from simple base substitutions be as diverse as gene duplication, deletions, alternative splicing, gene recombination, domain shuffling, retrotransposition, and gene conversion. Further, variable regulation of gene expression may have played a role.}, } @article {pmid25283544, year = {2015}, author = {Jiang, J and Wu, S and Wang, J and Feng, Y}, title = {AHL-type quorum sensing and its regulation on symplasmata formation in Pantoea agglomerans YS19.}, journal = {Journal of basic microbiology}, volume = {55}, number = {5}, pages = {607-616}, doi = {10.1002/jobm.201400472}, pmid = {25283544}, issn = {1521-4028}, mesh = {Acyl-Butyrolactones/chemistry/*metabolism ; Bacterial Adhesion/*drug effects ; Cloning, Molecular ; Cluster Analysis ; Conserved Sequence ; Endophytes/genetics/growth & development/metabolism/*physiology ; *Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Molecular Sequence Data ; Oryza/microbiology ; Pantoea/genetics/growth & development/metabolism/*physiology ; Phylogeny ; *Quorum Sensing ; Sequence Analysis, DNA ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Pantoea agglomerans YS19, an endophytic diazotrophic bacterium isolated from rice, is characterized by the formation of multicellular aggregate structure called symplasmata, which not only bestow the strong stress-resistance of the bacterium, but also contribute to the specific adaptation in the endophyte-host association. Acyl-homoserine lactones (AHLs), as the important signal molecule in the quorum sensing (QS) system of gram-negative bacteria, were demonstrated to regulate motility, cell-aggregation, and other bacterial behaviors. Here, the production of AHL by P. agglomerans YS19 and its regulation on the symplasmata formation were studied. It was revealed that the production of AHL by YS19 was initiated at the exponential growth stage and from then on, reached the peak values at the stationary growth stage in LB medium. The AHL was identified as N-3-oxooctanoyl-L-homoserine lactone (OOHL) by MALDI-TOF-MS analysis. The AHL synthesis gene pagI and receptor gene pagR in YS19 were cloned and phylogenetic analysis showed that they were high conservative among strains in species of P. agglomerans. It was revealed that AHL promoted the bacterial growth and symplasmata formation of YS19. Meanwhile, the colonization ability and growth-promoting effect of YS19 on the host plant were also enhanced by AHL. These results strongly suggest the pleiotropic effects of the AHL-type QS system in endophytic life of the strain.}, } @article {pmid25283338, year = {2014}, author = {Dvořák, P and Casamatta, DA and Poulíčková, A and Hašler, P and Ondřej, V and Sanges, R}, title = {Synechococcus: 3 billion years of global dominance.}, journal = {Molecular ecology}, volume = {23}, number = {22}, pages = {5538-5551}, doi = {10.1111/mec.12948}, pmid = {25283338}, issn = {1365-294X}, mesh = {*Biological Evolution ; DNA, Bacterial/genetics ; *Gene Transfer, Horizontal ; *Genome, Bacterial ; Molecular Sequence Data ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Synechococcus/classification/*genetics ; }, abstract = {Cyanobacteria are among the most important primary producers on the Earth. However, the evolutionary forces driving cyanobacterial species diversity remain largely enigmatic due to both their distinction from macro-organisms and an undersampling of sequenced genomes. Thus, we present a new genome of a Synechococcus-like cyanobacterium from a novel evolutionary lineage. Further, we analyse all existing 16S rRNA sequences and genomes of Synechococcus-like cyanobacteria. Chronograms showed extremely polyphyletic relationships in Synechococcus, which has not been observed in any other cyanobacteria. Moreover, most Synechococcus lineages bifurcated after the Great Oxidation Event, including the most abundant marine picoplankton lineage. Quantification of horizontal gene transfer among 70 cyanobacterial genomes revealed significant differences among studied genomes. Horizontal gene transfer levels were not correlated with ecology, genome size or phenotype, but were correlated with the age of divergence. All findings were synthetized into a novel model of cyanobacterial evolution, characterized by serial convergence of the features, that is multicellularity and ecology.}, } @article {pmid25280764, year = {2014}, author = {Alegado, RA and King, N}, title = {Bacterial influences on animal origins.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {6}, number = {11}, pages = {a016162}, pmid = {25280764}, issn = {1943-0264}, support = {F32 GM086054/GM/NIGMS NIH HHS/United States ; R01 GM099533/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; 5F32GM086054/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*genetics/metabolism ; *Biological Evolution ; Cell Adhesion ; Choanoflagellata/genetics/*physiology ; Eukaryota/genetics/physiology ; Phagocytosis ; Phylogeny ; Signal Transduction ; }, abstract = {Animals evolved in seas teeming with bacteria, yet the influences of bacteria on animal origins are poorly understood. Comparisons among modern animals and their closest living relatives, the choanoflagellates, suggest that the first animals used flagellated collar cells to capture bacterial prey. The cell biology of prey capture, such as cell adhesion between predator and prey, involves mechanisms that may have been co-opted to mediate intercellular interactions during the evolution of animal multicellularity. Moreover, a history of bacterivory may have influenced the evolution of animal genomes by driving the evolution of genetic pathways for immunity and facilitating lateral gene transfer. Understanding the interactions between bacteria and the progenitors of animals may help to explain the myriad ways in which bacteria shape the biology of modern animals, including ourselves.}, } @article {pmid25276334, year = {2014}, author = {Thacker, RW and Díaz, MC and Kerner, A and Vignes-Lebbe, R and Segerdell, E and Haendel, MA and Mungall, CJ}, title = {The Porifera Ontology (PORO): enhancing sponge systematics with an anatomy ontology.}, journal = {Journal of biomedical semantics}, volume = {5}, number = {1}, pages = {39}, pmid = {25276334}, issn = {2041-1480}, abstract = {BACKGROUND: Porifera (sponges) are ancient basal metazoans that lack organs. They provide insight into key evolutionary transitions, such as the emergence of multicellularity and the nervous system. In addition, their ability to synthesize unusual compounds offers potential biotechnical applications. However, much of the knowledge of these organisms has not previously been codified in a machine-readable way using modern web standards.

RESULTS: The Porifera Ontology is intended as a standardized coding system for sponge anatomical features currently used in systematics. The ontology is available from http://purl.obolibrary.org/obo/poro.owl, or from the project homepage http://porifera-ontology.googlecode.com/. The version referred to in this manuscript is permanently available from http://purl.obolibrary.org/obo/poro/releases/2014-03-06/.

CONCLUSIONS: By standardizing character representations, we hope to facilitate more rapid description and identification of sponge taxa, to allow integration with other evolutionary database systems, and to perform character mapping across the major clades of sponges to better understand the evolution of morphological features. Future applications of the ontology will focus on creating (1) ontology-based species descriptions; (2) taxonomic keys that use the nested terms of the ontology to more quickly facilitate species identifications; and (3) methods to map anatomical characters onto molecular phylogenies of sponges. In addition to modern taxa, the ontology is being extended to include features of fossil taxa.}, } @article {pmid25252979, year = {2014}, author = {Chen, L and Xiao, S and Pang, K and Zhou, C and Yuan, X}, title = {Cell differentiation and germ-soma separation in Ediacaran animal embryo-like fossils.}, journal = {Nature}, volume = {516}, number = {7530}, pages = {238-241}, pmid = {25252979}, issn = {1476-4687}, mesh = {Animals ; Apoptosis ; Blastula/cytology ; *Cell Differentiation ; China ; Chlorophyta/cytology ; Embryo, Nonmammalian/*cytology ; Eukaryotic Cells/classification/cytology ; *Fossils ; *Phylogeny ; }, abstract = {Phosphorites of the Ediacaran Doushantuo Formation (∼600 million years old) yield spheroidal microfossils with a palintomic cell cleavage pattern. These fossils have been variously interpreted as sulphur-oxidizing bacteria, unicellular protists, mesomycetozoean-like holozoans, green algae akin to Volvox, and blastula embryos of early metazoans or bilaterian animals. However, their complete life cycle is unknown and it is uncertain whether they had a cellularly differentiated ontogenetic stage, making it difficult to test their various phylogenetic interpretations. Here we describe new spheroidal fossils from black phosphorites of the Doushantuo Formation that have been overlooked in previous studies. These fossils represent later developmental stages of previously published blastula-like fossils, and they show evidence for cell differentiation, germ-soma separation, and programmed cell death. Their complex multicellularity is inconsistent with a phylogenetic affinity with bacteria, unicellular protists, or mesomycetozoean-like holozoans. Available evidence also indicates that the Doushantuo fossils are unlikely crown-group animals or volvocine green algae. We conclude that an affinity with cellularly differentiated multicellular eukaryotes, including stem-group animals or algae, is likely but more data are needed to constrain further the exact phylogenetic affinity of the Doushantuo fossils.}, } @article {pmid25249249, year = {2015}, author = {Kang, L and Michalak, P}, title = {The evolution of cancer-related genes in hominoids.}, journal = {Journal of molecular evolution}, volume = {80}, number = {1}, pages = {37-41}, pmid = {25249249}, issn = {1432-1432}, mesh = {Animals ; Base Sequence ; *Evolution, Molecular ; *Genes, Tumor Suppressor ; Hominidae/*genetics ; Humans ; *Oncogenes ; Sequence Homology, Nucleic Acid ; }, abstract = {The evolution of cancer suppression is essential for the maintenance of multicellularity. The lack of correlation between body size and cancer risk across species, known as Peto's paradox, suggests that genetic variation in cancer resistance is sufficient to compensate for increases of cell numbers in bigger animals. To assess evolutionary dynamics of cancer-related genes, we analyzed Ka, Ks,and Ka/Ks values in 120 oncogenes and tumor suppressor genes (TSG) among seven hominoid species, including two extinct species, Neanderthal and Denisovan. Ka/Ks of tumor suppressor genes tended to be higher relative to that of oncogenes, consistent with relaxed purifying selection acting on the former. Ka/Ks values were positively correlated with TSG scores, but negatively correlated with oncogene scores, suggesting opposing selection pressures operating on the two groups of cancer-related genes. Additionally, we found 108 species-divergent substitutions that were prevalent germline genotypes in some species but in humans appeared only as somatic cancerous mutations. Better understanding the resistance to cancer may lead to new methods of cancer prevention in humans.}, } @article {pmid25248478, year = {2014}, author = {Delidakis, C and Monastirioti, M and Magadi, SS}, title = {E(spl): genetic, developmental, and evolutionary aspects of a group of invertebrate Hes proteins with close ties to Notch signaling.}, journal = {Current topics in developmental biology}, volume = {110}, number = {}, pages = {217-262}, doi = {10.1016/B978-0-12-405943-6.00006-3}, pmid = {25248478}, issn = {1557-8933}, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Central Nervous System/embryology ; Drosophila/embryology/genetics/metabolism ; Drosophila Proteins/genetics/*metabolism ; Embryo, Nonmammalian ; Evolution, Molecular ; *Gene Expression Regulation ; Invertebrates/genetics/*metabolism ; Neurons/cytology/physiology ; Receptors, Notch/*metabolism ; Repressor Proteins/genetics/*metabolism ; }, abstract = {Enhancer-of-split (E(spl)) was genetically characterized in Drosophila as a dominant mutation that interacts with an allele of Notch, the receptor in a multipurpose signaling pathway throughout development. Although dominant mutations are often not informative of the normal gene function, E(spl) turned out to encode a family of seven paralogous basic helix-loop-helix proteins of utmost importance in the implementation of the Notch signal in the receiving cell. They are transcriptionally induced by Notch in almost every instance where the signal is deployed, and they participate in numerous feedback circuits, where they interface with a panoply of additional more tissue-specific Notch targets to ensure the proper signaling outcome. Besides the bHLH domain, E(spl) contain a characteristic Orange domain and are classified in the Hes (hairy and enhancer-of-split) branch of the bHLH-Orange proteins. They act as DNA-binding repressors in close collaboration with the corepressor Groucho. In this review, we will focus on the regulation of E(spl) expression and on the function of E(spl) proteins. In the latter section, we will present some of the best-studied developmental events where E(spl) function has been analysed as well as the molecular mechanism of E(spl) activity that has transpired. Finally, we will review the evolution of this protein family, which, albeit of relatively recent origin, present only in insects and crustaceans, has undergone extensive diversification, including gene loss and duplication. Importantly, many of the characteristics of E(spl) proteins are more deeply rooted in the very ancient larger bHLH-O family, which seems to have forged a connection with the Notch pathway from the very beginning of multicellular animal life.}, } @article {pmid25246576, year = {2014}, author = {Daum, G and Medzihradszky, A and Suzaki, T and Lohmann, JU}, title = {A mechanistic framework for noncell autonomous stem cell induction in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {40}, pages = {14619-14624}, pmid = {25246576}, issn = {1091-6490}, mesh = {Arabidopsis/cytology/*genetics/metabolism ; Arabidopsis Proteins/chemistry/*genetics/metabolism ; Cell Communication/genetics ; Fluorescence Resonance Energy Transfer ; Gene Expression Regulation, Plant ; Homeodomain Proteins/chemistry/*genetics/metabolism ; In Situ Hybridization ; Luminescent Proteins/genetics/metabolism ; Meristem/cytology/*metabolism ; Microscopy, Confocal ; Plant Stems/cytology/genetics/metabolism ; Plants, Genetically Modified ; Plasmodesmata/metabolism ; Protein Multimerization ; Protein Transport/genetics ; Signal Transduction/genetics ; Stem Cells/*metabolism ; }, abstract = {Cell-cell communication is essential for multicellular development and, consequently, evolution has brought about an array of distinct mechanisms serving this purpose. Consistently, induction and maintenance of stem cell fate by noncell autonomous signals is a feature shared by many organisms and may depend on secreted factors, direct cell-cell contact, matrix interactions, or a combination of these mechanisms. Although many basic cellular processes are well conserved between animals and plants, cell-to-cell signaling is one function where substantial diversity has arisen between the two kingdoms of life. One of the most striking differences is the presence of cytoplasmic bridges, called plasmodesmata, which facilitate the exchange of molecules between neighboring plant cells and provide a unique route for cell-cell communication in the plant lineage. Here, we provide evidence that the stem cell inducing transcription factor WUSCHEL (WUS), expressed in the niche, moves to the stem cells via plasmodesmata in a highly regulated fashion and that this movement is required for WUS function and, thus, stem cell activity in Arabidopsis thaliana. We show that cell context-independent mobility is encoded in the WUS protein sequence and mediated by multiple domains. Finally, we demonstrate that parts of the protein that restrict movement are required for WUS homodimerization, suggesting that formation of WUS dimers might contribute to the regulation of apical stem cell activity.}, } @article {pmid25239794, year = {2014}, author = {Iriarte, A and Jara, E and Leytón, L and Diana, L and Musto, H}, title = {General trends in selectively driven codon usage biases in the domain archaea.}, journal = {Journal of molecular evolution}, volume = {79}, number = {3-4}, pages = {105-110}, pmid = {25239794}, issn = {1432-1432}, mesh = {Archaea/*genetics ; *Codon ; *Evolution, Molecular ; *Phylogeny ; }, abstract = {Since the advent of rapid techniques for sequencing DNA in the mid 70's, it became clear that all codons coding for the same amino acid are not used according to neutral expectations. In the last 30 years, several theories were proposed for explaining this fact. However, the most important concepts were the result of analyses carried out in Bacteria, and unicellular and multicellular eukaryotes like mammals (in other words, in two of the three Domains of life). In this communication, we study the main forces that shape codon usage in Archaeae under an evolutionary perspective. This is important because, as known, the orthologous genes related with the informational system in this Domain (replication, transcription and translation) are more similar to eukaryotes than to Bacteria. Our results show that the effect of selection acting at the level of translation is present in the Domain but mainly restricted to only a phylum (Euryarchaeota) and therefore is not as extended as in Bacteria. Besides, we describe the phylogenetic distribution of translational optimal codons and estimate the effect of selection acting at the level of accuracy. Finally, we discuss these results under some peculiarities that characterize this Domain.}, } @article {pmid25238093, year = {2014}, author = {Diefenbach, A and Colonna, M and Koyasu, S}, title = {Development, differentiation, and diversity of innate lymphoid cells.}, journal = {Immunity}, volume = {41}, number = {3}, pages = {354-365}, pmid = {25238093}, issn = {1097-4180}, support = {R01 DE021255/DE/NIDCR NIH HHS/United States ; 1U01AI095542/AI/NIAID NIH HHS/United States ; R01DE021255/DE/NIDCR NIH HHS/United States ; R21CA16719/CA/NCI NIH HHS/United States ; R21 CA167192/CA/NCI NIH HHS/United States ; U01 AI095542/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/immunology ; Cell Lineage/immunology ; Cytokines/*immunology ; Gene Expression Regulation/immunology ; Humans ; Immunity, Innate ; Killer Cells, Natural/*immunology ; Mice ; Signal Transduction/immunology ; Stem Cells/*immunology ; T-Lymphocytes, Helper-Inducer/*immunology ; Tight Junctions/immunology ; Transcription, Genetic ; }, abstract = {Recent years have witnessed the discovery of an unprecedented complexity in innate lymphocyte lineages, now collectively referred to as innate lymphoid cells (ILCs). ILCs are preferentially located at barrier surfaces and are important for protection against pathogens and for the maintenance of organ homeostasis. Inappropriate activation of ILCs has been linked to the pathogenesis of inflammatory and autoimmune disorders. Recent evidence suggests that ILCs can be grouped into two separate lineages, cytotoxic ILCs represented by conventional natural killer (cNK) cells and cytokine-producing helper-like ILCs (i.e., ILC1s, ILC2s, ILC3s). We will focus here on current work in humans and mice that has identified core transcriptional circuitry required for the commitment of lymphoid progenitors to the ILC lineage. The striking similarities in transcriptional control of ILC and T cell lineages reveal important insights into the evolution of transcriptional programs required to protect multicellular organisms against infections and to fortify barrier surfaces.}, } @article {pmid25233196, year = {2014}, author = {Libby, E and Ratcliff, W and Travisano, M and Kerr, B}, title = {Geometry shapes evolution of early multicellularity.}, journal = {PLoS computational biology}, volume = {10}, number = {9}, pages = {e1003803}, pmid = {25233196}, issn = {1553-7358}, mesh = {Apoptosis ; *Biological Evolution ; Cell Physiological Phenomena/*physiology ; Computational Biology ; *Models, Biological ; Yeasts/cytology/physiology ; }, abstract = {Organisms have increased in complexity through a series of major evolutionary transitions, in which formerly autonomous entities become parts of a novel higher-level entity. One intriguing feature of the higher-level entity after some major transitions is a division of reproductive labor among its lower-level units in which reproduction is the sole responsibility of a subset of units. Although it can have clear benefits once established, it is unknown how such reproductive division of labor originates. We consider a recent evolution experiment on the yeast Saccharomyces cerevisiae as a unique platform to address the issue of reproductive differentiation during an evolutionary transition in individuality. In the experiment, independent yeast lineages evolved a multicellular "snowflake-like" cluster formed in response to gravity selection. Shortly after the evolution of clusters, the yeast evolved higher rates of cell death. While cell death enables clusters to split apart and form new groups, it also reduces their performance in the face of gravity selection. To understand the selective value of increased cell death, we create a mathematical model of the cellular arrangement within snowflake yeast clusters. The model reveals that the mechanism of cell death and the geometry of the snowflake interact in complex, evolutionarily important ways. We find that the organization of snowflake yeast imposes powerful limitations on the available space for new cell growth. By dying more frequently, cells in clusters avoid encountering space limitations, and, paradoxically, reach higher numbers. In addition, selection for particular group sizes can explain the increased rate of apoptosis both in terms of total cell number and total numbers of collectives. Thus, by considering the geometry of a primitive multicellular organism we can gain insight into the initial emergence of reproductive division of labor during an evolutionary transition in individuality.}, } @article {pmid25230797, year = {2014}, author = {Armenta-Medina, D and Segovia, L and Perez-Rueda, E}, title = {Comparative genomics of nucleotide metabolism: a tour to the past of the three cellular domains of life.}, journal = {BMC genomics}, volume = {15}, number = {1}, pages = {800}, pmid = {25230797}, issn = {1471-2164}, mesh = {Archaea/*genetics/metabolism ; Bacteria/*genetics/metabolism ; Eukaryota/*genetics/metabolism ; *Evolution, Molecular ; *Genomics ; Nucleotides/*metabolism ; }, abstract = {BACKGROUND: Nucleotide metabolism is central to all biological systems, due to their essential role in genetic information and energy transfer, which in turn suggests its possible presence in the last common ancestor (LCA) of Bacteria, Archaea and Eukarya. In this context, elucidation of the contribution of the origin and diversification of de novo and salvage pathways of nucleotide metabolism will allow us to understand the links between the enzymatic steps associated with the LCA and the emergence of the first metabolic pathways.

RESULTS: In this work, the taxonomical distribution of the enzymes associated with nucleotide metabolism was evaluated in 1,606 complete genomes. 151 sequence profiles associated with 120 enzymatic reactions were used. The evaluation was based on profile comparisons, using RPS-Blast. Organisms were clustered based on their taxonomical classifications, in order to obtain a normalized measure of the taxonomical distribution of enzymes according to the average of presence/absence of enzymes per genus, which in turn was used for the second step, to calculate the average presence/absence of enzymes per Clade.

CONCLUSION: From these analyses, it was suggested that divergence at the enzymatic level correlates with environmental changes and related modifications of the cell wall and membranes that took place during cell evolution. Specifically, the divergence of the 5-(carboxyamino) imidazole ribonucleotide mutase to phosphoribosylaminoimidazole carboxylase could be related to the emergence of multicellularity in eukaryotic cells. In addition, segments of salvage and de novo pathways were probably complementary in the LCA to the synthesis of purines and pyrimidines. We also suggest that a large portion of the pathway to inosine 5'-monophosphate (IMP) in purines could have been involved in thiamine synthesis or its derivatives in early stages of cellular evolution, correlating with the fact that these molecules may have played an active role in the protein-RNA world. The analysis presented here provides general observations concerning the adaptation of the enzymatic steps in the early stages of the emergence of life and the LCA.}, } @article {pmid25227255, year = {2015}, author = {Auld, SK and Tinsley, MC}, title = {The evolutionary ecology of complex lifecycle parasites: linking phenomena with mechanisms.}, journal = {Heredity}, volume = {114}, number = {2}, pages = {125-132}, pmid = {25227255}, issn = {1365-2540}, mesh = {Animals ; *Biological Evolution ; Host-Parasite Interactions/*genetics ; *Life Cycle Stages ; Models, Biological ; Parasites/genetics/*growth & development ; Parasitic Diseases/genetics/immunology/parasitology ; }, abstract = {Many parasitic infections, including those of humans, are caused by complex lifecycle parasites (CLPs): parasites that sequentially infect different hosts over the course of their lifecycle. CLPs come from a wide range of taxonomic groups-from single-celled bacteria to multicellular flatworms-yet share many common features in their life histories. Theory tells us when CLPs should be favoured by selection, but more empirical studies are required in order to quantify the costs and benefits of having a complex lifecycle, especially in parasites that facultatively vary their lifecycle complexity. In this article, we identify ecological conditions that favour CLPs over their simple lifecycle counterparts and highlight how a complex lifecycle can alter transmission rate and trade-offs between growth and reproduction. We show that CLPs participate in dynamic host-parasite coevolution, as more mobile hosts can fuel CLP adaptation to less mobile hosts. Then, we argue that a more general understanding of the evolutionary ecology of CLPs is essential for the development of effective frameworks to manage the many diseases they cause. More research is needed identifying the genetics of infection mechanisms used by CLPs, particularly into the role of gene duplication and neofunctionalisation in lifecycle evolution. We propose that testing for signatures of selection in infection genes will reveal much about how and when complex lifecycles evolved, and will help quantify complex patterns of coevolution between CLPs and their various hosts. Finally, we emphasise four key areas where new research approaches will provide fertile opportunities to advance this field.}, } @article {pmid25227035, year = {2014}, author = {Zhang, Z and Yi, X and Peng, H}, title = {A novel framework of tissue membrane systems for image fusion.}, journal = {Bio-medical materials and engineering}, volume = {24}, number = {6}, pages = {3259-3266}, doi = {10.3233/BME-141148}, pmid = {25227035}, issn = {1878-3619}, mesh = {*Algorithms ; Biomimetics/*methods ; Image Enhancement/methods ; Image Interpretation, Computer-Assisted/*methods ; Membranes ; Pattern Recognition, Automated/*methods ; Photography/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; *Subtraction Technique ; }, abstract = {This paper proposes a tissue membrane system-based framework to deal with the optimal image fusion problem. A spatial domain fusion algorithm is given, and a tissue membrane system of multiple cells is used as its computing framework. Based on the multicellular structure and inherent communication mechanism of the tissue membrane system, an improved velocity-position model is developed. The performance of the fusion framework is studied with comparison of several traditional fusion methods as well as genetic algorithm (GA)-based and differential evolution (DE)-based spatial domain fusion methods. Experimental results show that the proposed fusion framework is superior or comparable to the other methods and can be efficiently used for image fusion.}, } @article {pmid25223736, year = {2015}, author = {Gruber, R}, title = {Molecular and cellular basis of bone resorption.}, journal = {Wiener medizinische Wochenschrift (1946)}, volume = {165}, number = {3-4}, pages = {48-53}, pmid = {25223736}, issn = {1563-258X}, mesh = {Animals ; Biphenyl Compounds/therapeutic use ; Bone Remodeling/drug effects/genetics/physiology ; Bone Resorption/drug therapy/*genetics/*physiopathology ; Cathepsin K/antagonists & inhibitors/genetics/physiology ; Humans ; Osteoblasts/drug effects/*physiology ; Osteoclasts/drug effects/*physiology ; Osteoporosis/drug therapy/genetics/physiopathology ; RANK Ligand/genetics/physiology ; }, abstract = {Osteoclast research has an exciting history and a challenging future. More than 3 decades ago, it became evident that bone-resorbing osteoclasts are of hematopoietic origin and are ultimately linked to the "basic multicellular unit," where they team up with the other cell types, including bone-forming osteoblasts. Since 2 decades, we have learned about the signaling pathways controlling genes relevant for osteoclastogenesis and bone resorption. It took another decade until the hypothesized "osteoclast differentiation" factor was discovered and was translated into an approved pharmacologic strategy. Here, the focus is on another molecular target, cathepsin K, a cysteine protease being released by the osteoclast into the resorption compartment. Genetic deletion and pharmacological blocking of cathepsin K reduces bone resorption but with ongoing bone formation. This observation not only holds great promise to become a new pharmacologic strategy, but it also provides new insights into the coordinated work of cells in the "basic multicellular unit" and thus, bridges the history and future of osteoclast research. This article is a short primer on osteoclast biology for readers of the special issue on odanacatib, a cathepsin K inhibitor.}, } @article {pmid25185827, year = {2014}, author = {Joerger, AC and Wilcken, R and Andreeva, A}, title = {Tracing the evolution of the p53 tetramerization domain.}, journal = {Structure (London, England : 1993)}, volume = {22}, number = {9}, pages = {1301-1310}, pmid = {25185827}, issn = {1878-4186}, support = {MC_EX_G0901534/MRC_/Medical Research Council/United Kingdom ; MC_U105192716/MRC_/Medical Research Council/United Kingdom ; G0901534/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; Conserved Sequence ; Crystallography, X-Ray ; Evolution, Molecular ; Humans ; Molecular Sequence Data ; Phylogeny ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Sequence Analysis, Protein ; Tumor Suppressor Protein p53/*chemistry/genetics ; Zebrafish ; Zebrafish Proteins/*chemistry/genetics ; }, abstract = {The tetrameric transcription factors p53, p63, and p73 evolved from a common ancestor and play key roles in tumor suppression and development. Surprisingly, p63 and p73 require a second helix in their tetramerization domain for the formation of stable tetramers that is absent in human p53, raising questions about the evolutionary processes leading to diversification. Here we determined the crystal structure of the zebrafish p53 tetramerization domain, which contains a second helix, reminiscent of p63 and p73, combined with p53-like features. Through comprehensive phylogenetic analyses, we systematically traced the evolution of vertebrate p53 family oligomerization domains back to the beginning of multicellular life. We provide evidence that their last common ancestor also had an extended p63/p73-like domain and pinpoint evolutionary events that shaped this domain during vertebrate radiation. Domain compaction and transformation of a structured into a flexible, intrinsically disordered region may have contributed to the expansion of the human p53 interactome.}, } @article {pmid25184567, year = {2014}, author = {Furuse, Y and Finethy, R and Saka, HA and Xet-Mull, AM and Sisk, DM and Smith, KL and Lee, S and Coers, J and Valdivia, RH and Tobin, DM and Cullen, BR}, title = {Search for microRNAs expressed by intracellular bacterial pathogens in infected mammalian cells.}, journal = {PloS one}, volume = {9}, number = {9}, pages = {e106434}, pmid = {25184567}, issn = {1932-6203}, support = {R01-AI100759/AI/NIAID NIH HHS/United States ; T32 GM007184/GM/NIGMS NIH HHS/United States ; R01 AI100759/AI/NIAID NIH HHS/United States ; P30-AI064518/AI/NIAID NIH HHS/United States ; 1DP2-OD008614-01/OD/NIH HHS/United States ; P30 AI064518/AI/NIAID NIH HHS/United States ; DP2 OD008614/OD/NIH HHS/United States ; }, mesh = {Carboxypeptidases/*genetics ; Chlamydia/genetics/isolation & purification ; Gene Expression Regulation ; *High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/*genetics ; Legionella/genetics/isolation & purification ; MicroRNAs/genetics/*isolation & purification ; Mycobacterium tuberculosis/genetics/isolation & purification ; RNA, Bacterial/genetics/isolation & purification ; }, abstract = {MicroRNAs are expressed by all multicellular organisms and play a critical role as post-transcriptional regulators of gene expression. Moreover, different microRNA species are known to influence the progression of a range of different diseases, including cancer and microbial infections. A number of different human viruses also encode microRNAs that can attenuate cellular innate immune responses and promote viral replication, and a fungal pathogen that infects plants has recently been shown to express microRNAs in infected cells that repress host cell immune responses and promote fungal pathogenesis. Here, we have used deep sequencing of total expressed small RNAs, as well as small RNAs associated with the cellular RNA-induced silencing complex RISC, to search for microRNAs that are potentially expressed by intracellular bacterial pathogens and translocated into infected animal cells. In the case of Legionella and Chlamydia and the two mycobacterial species M. smegmatis and M. tuberculosis, we failed to detect any bacterial small RNAs that had the characteristics expected for authentic microRNAs, although large numbers of small RNAs of bacterial origin could be recovered. However, a third mycobacterial species, M. marinum, did express an ∼ 23-nt small RNA that was bound by RISC and derived from an RNA stem-loop with the characteristics expected for a pre-microRNA. While intracellular expression of this candidate bacterial microRNA was too low to effectively repress target mRNA species in infected cultured cells in vitro, artificial overexpression of this potential bacterial pre-microRNA did result in the efficient repression of a target mRNA. This bacterial small RNA therefore represents the first candidate microRNA of bacterial origin.}, } @article {pmid25174994, year = {2014}, author = {Bosch, TC}, title = {Rethinking the role of immunity: lessons from Hydra.}, journal = {Trends in immunology}, volume = {35}, number = {10}, pages = {495-502}, doi = {10.1016/j.it.2014.07.008}, pmid = {25174994}, issn = {1471-4981}, mesh = {Animals ; Biological Evolution ; Humans ; Hydra/*immunology ; Immunity, Innate/*immunology ; Receptors, Pattern Recognition/immunology ; }, abstract = {The ability of multicellular organisms to detect and respond to microorganisms is fundamental and has ancient evolutionary origins. In this review, I evaluate our current understanding of the evolution of epithelial-based innate immunity in Hydra, an apparently simple animal that shares deep evolutionary connections with all animals, including humans. I highlight growing evidence that the innate immune system with its host-specific antimicrobial peptides and rich repertoire of pattern recognition receptors has evolved in response to the need for controlling resident beneficial microbes rather than to defend against invasive pathogens. These findings provide new insight into how developmental pathways beyond those associated with the immune system, such as stem cell transcriptional programs, interact with environmental cues such as microbes.}, } @article {pmid25164483, year = {2014}, author = {Hubka, V and Réblová, M and Rehulka, J and Selbmann, L and Isola, D and de Hoog, SG and Kolařík, M}, title = {Bradymyces gen. nov. (Chaetothyriales, Trichomeriaceae), a new ascomycete genus accommodating poorly differentiated melanized fungi.}, journal = {Antonie van Leeuwenhoek}, volume = {106}, number = {5}, pages = {979-992}, doi = {10.1007/s10482-014-0267-4}, pmid = {25164483}, issn = {1572-9699}, mesh = {Animals ; Ascomycota/*classification/cytology/genetics/*isolation & purification ; Cluster Analysis ; DNA, Fungal/chemistry/genetics ; DNA, Intergenic/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Environmental Microbiology ; Microscopy ; Molecular Sequence Data ; Oncorhynchus mykiss/microbiology ; Phylogeny ; RNA, Ribosomal, 18S/genetics ; RNA, Ribosomal, 28S/genetics ; Sequence Analysis, DNA ; Temperature ; Tubulin/genetics ; }, abstract = {Three slow growing, melanized and morphologically poorly differentiated fungal strains were isolated from a hyperaemic focus near the enlarged spleen of a farmed rainbow trout (Oncorhynchus mykiss) and from a rock collected at 3,200 m a. s. l. (Alps, Italy). Two phylogenetic analyses of the combined nuc18S and nuc28S rDNA and ITS rDNA and β-tubulin sequences showed that these isolates belong to the Trichomeriaceae, a family of the ascomycete order Chaetothyriales containing black yeasts that cause infections in humans and animals. The strains form a well-supported monophyletic clade. The new genus Bradymyces, with two new species, Bradymyces oncorhynchi and Bradymyces alpinus, is proposed based on phylogenetic, ecophysiological and morphological data. It is characterized by the presence of moniliform hyphae, blastic proliferation, endoconidia, multicellular and muriform bodies, and bodies with dark fragmented incrustations on the surface. Bradymyces most closely resembles members of Knufia. The ex-type isolate of B. oncorhynchi CCF 4369(T) (= CBS 133066(T) = CCFEE 6134(T)) represents the first case of a Trichomeriaceae member isolated from cold-blooded water vertebrates. B. alpinus [ex-type strain CCFEE 5493(T) (= CBS 138368(T) = CCF 4803(T))] is represented by two isolates from a single locality in the Alps and in contrast to B. oncorhynchi shows overall slower growth parameters and does not grow at 25 °C.}, } @article {pmid25159814, year = {2014}, author = {Huvet, M and Stumpf, MP}, title = {Overlapping genes: a window on gene evolvability.}, journal = {BMC genomics}, volume = {15}, number = {1}, pages = {721}, pmid = {25159814}, issn = {1471-2164}, support = {BB/F013566/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Bacteria/classification/genetics ; Codon, Initiator ; Codon, Terminator ; Computational Biology ; *Evolution, Molecular ; *Genes, Overlapping ; Genome ; Genomics ; Phylogeny ; Untranslated Regions ; }, abstract = {BACKGROUND: The forces underlying genome architecture and organization are still only poorly understood in detail. Overlapping genes (genes partially or entirely overlapping) represent a genomic feature that is shared widely across biological organisms ranging from viruses to multi-cellular organisms. In bacteria, a third of the annotated genes are involved in an overlap. Despite the widespread nature of this arrangement, its evolutionary origins and biological ramifications have so far eluded explanation.

RESULTS: Here we present a comparative approach using information from 699 bacterial genomes that sheds light on the evolutionary dynamics of overlapping genes. We show that these structures exhibit high levels of plasticity.

CONCLUSIONS: We propose a simple model allowing us to explain the observed properties of overlapping genes based on the importance of initiation and termination of transcriptional and translational processes. We believe that taking into account the processes leading to the expression of protein-coding genes hold the key to the understanding of overlapping genes structures.}, } @article {pmid25158977, year = {2014}, author = {Yin, K and Ueda, M and Takagi, H and Kajihara, T and Sugamata Aki, S and Nobusawa, T and Umeda-Hara, C and Umeda, M}, title = {A dual-color marker system for in vivo visualization of cell cycle progression in Arabidopsis.}, journal = {The Plant journal : for cell and molecular biology}, volume = {80}, number = {3}, pages = {541-552}, doi = {10.1111/tpj.12652}, pmid = {25158977}, issn = {1365-313X}, mesh = {Arabidopsis/cytology/genetics/*metabolism ; Cell Cycle/genetics ; *DNA Replication ; G2 Phase/genetics ; *Gene Expression Regulation, Plant ; Genes, Reporter ; Histones/*metabolism ; Mitosis ; Plant Roots/genetics ; Time-Lapse Imaging/*methods ; }, abstract = {Visualization of the spatiotemporal pattern of cell division is crucial to understand how multicellular organisms develop and how they modify their growth in response to varying environmental conditions. The mitotic cell cycle consists of four phases: S (DNA replication), M (mitosis and cytokinesis), and the intervening G1 and G2 phases; however, only G2/M-specific markers are currently available in plants, making it difficult to measure cell cycle duration and to analyze changes in cell cycle progression in living tissues. Here, we developed another cell cycle marker that labels S-phase cells by manipulating Arabidopsis CDT1a, which functions in DNA replication origin licensing. Truncations of the CDT1a coding sequence revealed that its carboxy-terminal region is responsible for proteasome-mediated degradation at late G2 or in early mitosis. We therefore expressed this region as a red fluorescent protein fusion protein under the S-specific promoter of a histone 3.1-type gene, HISTONE THREE RELATED2 (HTR2), to generate an S/G2 marker. Combining this marker with the G2/M-specific CYCB1-GFP marker enabled us to visualize both S to G2 and G2 to M cell cycle stages, and thus yielded an essential tool for time-lapse imaging of cell cycle progression. The resultant dual-color marker system, Cell Cycle Tracking in Plant Cells (Cytrap), also allowed us to identify root cells in the last mitotic cell cycle before they entered the endocycle. Our results demonstrate that Cytrap is a powerful tool for in vivo monitoring of the plant cell cycle, and thus for deepening our understanding of cell cycle regulation in particular cell types during organ development.}, } @article {pmid25150025, year = {2014}, author = {Ali, RH and Khan, AA}, title = {Tracing the evolution of FERM domain of Kindlins.}, journal = {Molecular phylogenetics and evolution}, volume = {80}, number = {}, pages = {193-204}, doi = {10.1016/j.ympev.2014.08.008}, pmid = {25150025}, issn = {1095-9513}, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Membrane Proteins/*genetics ; Molecular Sequence Data ; *Phylogeny ; *Protein Structure, Tertiary ; Sequence Analysis, DNA ; }, abstract = {Kindlin proteins represent a novel family of evolutionarily conserved FERM domain containing proteins (FDCPs) and are members of B4.1 superfamily. Kindlins consist of three conserved protein homologs in vertebrates: Kindlin-1, Kindlin-2 and Kindlin-3. All three homologs are associated with focal adhesions and are involved in Integrin activation. FERM domain of each Kindlin is bipartite and plays a key role in Integrin activation. A single ancestral Kindlin protein can be traced back to earliest metazoans, e.g., to Parazoa. This protein underwent multiple rounds of duplication in vertebrates, leading to the present Kindlin family. In this study, we trace phylogenetic and evolutionary history of Kindlin FERM domain with respect to FERM domain of other FDCPs. We show that FERM domain in Kindlin homologs is conserved among Kindlins but amount of conservation is less in comparison with FERM domain of other members in B4.1 superfamily. Furthermore, insertion of Pleckstrin Homology like domain in Kindlin FERM domain has important evolutionary and functional consequences. Important residues in Kindlins are traced and ranked according to their evolutionary significance. The structural and functional significance of high ranked residues is highlighted and validated by their known involvement in Kindlin associated diseases. In light of these findings, we hypothesize that FERM domain originated from a proto-Talin protein in unicellular or proto-multicellular organism and advent of multi-cellularity was accompanied by burst of FDCPs, which supported multi-cellularity functions required for complex organisms. This study helps in developing a better understanding of evolutionary history of FERM domain of FDCPs and the role of FERM domain in metazoan evolution.}, } @article {pmid25146840, year = {2015}, author = {Ortiz, MF and Wallau, GL and Graichen, DÂ and Loreto, EL}, title = {An evaluation of the ecological relationship between Drosophila species and their parasitoid wasps as an opportunity for horizontal transposon transfer.}, journal = {Molecular genetics and genomics : MGG}, volume = {290}, number = {1}, pages = {67-78}, pmid = {25146840}, issn = {1617-4623}, mesh = {Animals ; Base Sequence ; DNA Transposable Elements/*genetics ; Drosophila/microbiology/*parasitology ; Gene Transfer, Horizontal/*genetics ; Genes, Mitochondrial ; Genome, Insect/genetics ; *Host-Parasite Interactions ; Phylogeny ; Reproducibility of Results ; Species Specificity ; Wasps/*physiology/virology ; Wolbachia/physiology ; }, abstract = {Evidences of horizontal transfer, the exchange of genetic material between reproductively isolated species, have accumulated over the last decades, including for multicellular eukaryotic organisms. However, the mechanisms and ecological relationships that promote such phenomenon is still poorly known. Host-parasite interaction is one type of relationship usually pointed in the literature that could potentially increase the probability of the horizontal transfer between species, because the species involved in such relationships are generally in close contact. Transposable elements, which are well-known genomic parasites, are DNA entities that tend to be involved in horizontal transfer due to their ability to mobilize between different genomic locations. Using Drosophila species and their parasitoid wasps as a host-parasite model, we evaluated the hypothesis that horizontal transposon transfers (HTTs) are more frequent in this set of species than in species that do not exhibit a close ecological and phylogenetic relationship. For this purpose, we sequenced two sets of species using a metagenomic and single-species genomic sampling approach through next-generation DNA sequencing. The first set was composed of five generalist Drosophila (D. maculifrons, D. bandeirantorum, D. polymorpha, D. mercatorum and D. willistoni) species and their associated parasitoid wasps, whereas the second set was composed of D. incompta, which is a flower specialist species, and its parasitoid wasp. We did not find strong evidence of HTT in the two sets of Drosophila and wasp parasites. However, at least five cases of HTT were observed between the generalist and specialist Drosophila species. Moreover, we detected an HT event involving a Wolbachia lineage between generalist and specialist species, indicating that these endosymbiotic bacteria could play a role as HTT vectors. In summary, our results do not support the hypothesis of prevalent HTT between species with a host-parasite relationship, at least for the studied wasp-Drosophila pairs. Moreover, it suggests that other mechanisms or parasites are involved in promoting HTT between Drosophila species as the Wolbachia endosymbiotic bacteria.}, } @article {pmid25143284, year = {2014}, author = {Niklas, KJ and Cobb, ED and Kutschera, U}, title = {Did meiosis evolve before sex and the evolution of eukaryotic life cycles?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {36}, number = {11}, pages = {1091-1101}, doi = {10.1002/bies.201400045}, pmid = {25143284}, issn = {1521-1878}, mesh = {Animals ; Biological Evolution ; Chlorophyta ; Fertilization/*physiology ; Life Cycle Stages ; Meiosis/*genetics ; Polyploidy ; Reproduction, Asexual/*physiology ; *Sex ; }, abstract = {Biologists have long theorized about the evolution of life cycles, meiosis, and sexual reproduction. We revisit these topics and propose that the fundamental difference between life cycles is where and when multicellularity is expressed. We develop a scenario to explain the evolutionary transition from the life cycle of a unicellular organism to one in which multicellularity is expressed in either the haploid or diploid phase, or both. We propose further that meiosis might have evolved as a mechanism to correct for spontaneous whole-genome duplication (auto-polyploidy) and thus before the evolution of sexual reproduction sensu stricto (i.e. the formation of a diploid zygote via the fusion of haploid gametes) in the major eukaryotic clades. In addition, we propose, as others have, that sexual reproduction, which predominates in all eukaryotic clades, has many different advantages among which is that it produces variability among offspring and thus reduces sibling competition.}, } @article {pmid25133612, year = {2014}, author = {Peña, EJ and Ferriol, I and Sambade, A and Buschmann, H and Niehl, A and Elena, SF and Rubio, L and Heinlein, M}, title = {Experimental virus evolution reveals a role of plant microtubule dynamics and TORTIFOLIA1/SPIRAL2 in RNA trafficking.}, journal = {PloS one}, volume = {9}, number = {8}, pages = {e105364}, pmid = {25133612}, issn = {1932-6203}, mesh = {Arabidopsis/genetics/metabolism/*virology ; Arabidopsis Proteins/genetics/*metabolism ; Biological Evolution ; Host-Pathogen Interactions ; Microtubule-Associated Proteins/genetics/*metabolism ; Microtubules/genetics/*metabolism ; Mutation ; Plant Diseases/genetics/*virology ; RNA/genetics/metabolism ; *RNA Transport ; Tobacco Mosaic Virus/genetics/*physiology ; }, abstract = {The cytoskeleton is a dynamic network composed of filamentous polymers and regulatory proteins that provide a flexible structural scaffold to the cell and plays a fundamental role in developmental processes. Mutations that alter the spatial orientation of the cortical microtubule (MT) array of plants are known to cause important changes in the pattern of cell wall synthesis and developmental phenotypes; however, the consequences of such alterations on other MT-network-associated functions in the cytoplasm are not known. In vivo observations suggested a role of cortical MTs in the formation and movement of Tobacco mosaic virus (TMV) RNA complexes along the endoplasmic reticulum (ER). Thus, to probe the significance of dynamic MT behavior in the coordination of MT-network-associated functions related to TMV infection and, thus, in the formation and transport of RNA complexes in the cytoplasm, we performed an evolution experiment with TMV in Arabidopsis thaliana tor1/spr2 and tor2 mutants with specific defects in MT dynamics and asked whether TMV is sensitive to these changes. We show that the altered cytoskeleton induced genetic changes in TMV that were correlated with efficient spread of infection in the mutant hosts. These observations demonstrate a role of dynamic MT rearrangements and of the MT-associated protein TORTIFOLIA1/SPIRAL2 in cellular functions related to virus spread and indicate that MT dynamics and MT-associated proteins represent constraints for virus evolution and adaptation. The results highlight the importance of the dynamic plasticity of the MT network in directing cytoplasmic functions in macromolecular assembly and trafficking and illustrate the value of experimental virus evolution for addressing the cellular functions of dynamic, long-range order systems in multicellular organisms.}, } @article {pmid25123433, year = {2014}, author = {Zhang, J and Sun, P and Zhao, X and Ma, Z}, title = {PECM: prediction of extracellular matrix proteins using the concept of Chou's pseudo amino acid composition.}, journal = {Journal of theoretical biology}, volume = {363}, number = {}, pages = {412-418}, doi = {10.1016/j.jtbi.2014.08.002}, pmid = {25123433}, issn = {1095-8541}, mesh = {Amino Acids/*genetics ; *Evolution, Molecular ; Extracellular Matrix Proteins/*genetics ; Internet ; *Models, Genetic ; Proteomics/*methods ; *Software ; Support Vector Machine ; }, abstract = {The extracellular matrix proteins (ECMs) are widely found in the tissues of multicellular organisms. They consist of various secreted proteins, mainly polysaccharides and glycoproteins. The ECMs involve the exchange of materials and information between resident cells and the external environment. Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. In this paper, an accurate computational method named PECM is proposed for identifying ECMs. Here, we explore various sequence-derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. Rather than simply combining the features which may bring information redundancy and unwanted noises, we use Fisher-Markov selector and incremental feature selection approach to search the optimal feature subsets. Then, we train our model by the technique of support vector machine (SVM). PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. A web-server named PECM which implements the proposed approach is freely available at http://59.73.198.144:8088/PECM/.}, } @article {pmid25119834, year = {2014}, author = {Hill, J and Rom, S and Ramirez, SH and Persidsky, Y}, title = {Emerging roles of pericytes in the regulation of the neurovascular unit in health and disease.}, journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology}, volume = {9}, number = {5}, pages = {591-605}, pmid = {25119834}, issn = {1557-1904}, support = {AA015913/AA/NIAAA NIH HHS/United States ; R01 MH065151/MH/NIMH NIH HHS/United States ; P30 DA013429/DA/NIDA NIH HHS/United States ; NS086570/NS/NINDS NIH HHS/United States ; R37 AA015913/AA/NIAAA NIH HHS/United States ; MH65151/MH/NIMH NIH HHS/United States ; DA013429/DA/NIDA NIH HHS/United States ; R01 NS086570/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Blood-Brain Barrier/cytology/*metabolism/pathology ; Central Nervous System Diseases/*metabolism/pathology ; Endothelium, Vascular/cytology/*metabolism ; *Health Status ; Humans ; Pericytes/*physiology ; Signal Transduction/physiology ; }, abstract = {Pericytes of the central nervous system (CNS) are uniquely positioned within a multicellular structure termed the neurovascular unit (NVU) to provide crucial support to blood brain barrier (BBB) formation, maintenance, and stability. Numerous CNS diseases are associated with some aspect of BBB dysfunction. A dysfunction can manifest as one or multiple disruptions to any of the following barriers: physical, metabolic, immunological and transport barrier. A breach in the BBB can notably result in BBB hyper-permeability, endothelial activation and enhanced immune-endothelial interaction. How the BBB is regulated within this integrated unit remains largely unknown, especially as it relates to pericyte-endothelial interaction. We summarize the latest findings on pericyte origin, possible marker expression, and availability within different organ systems. We highlight pericyte-endothelial cell interactions, concentrating on extra- and intra- cellular signaling mechanisms linked to platelet derived growth factor-B, transforming growth factor -β, angiopoietins, Notch, and gap junctions. We discuss the role of pericytes in the NVU under inflammatory insult, focusing on how pericytes may indirectly affect leukocyte CNS infiltration, the direct role of pericyte-mediated basement membrane modifications, and immune responses. We review new findings of pericyte actions in CNS pathologies including Alzheimer's disease, stroke, multiple sclerosis, diabetic retinopathy, and HIV-1 infection. The uncovering of the regulatory role of pericytes on the BBB will provide key insight into how barrier integrity can be re-established during neuroinflammation.}, } @article {pmid25101061, year = {2014}, author = {Yan, J and Bradley, MD and Friedman, J and Welch, RD}, title = {Phenotypic profiling of ABC transporter coding genes in Myxococcus xanthus.}, journal = {Frontiers in microbiology}, volume = {5}, number = {}, pages = {352}, pmid = {25101061}, issn = {1664-302X}, abstract = {Information about a gene sometimes can be deduced by examining the impact of its mutation on phenotype. However, the genome-scale utility of the method is limited because, for nearly all model organisms, the majority of mutations result in little or no observable phenotypic impact. The cause of this is often attributed to robustness or redundancy within the genome, but that is only one plausible hypothesis. We examined a standard set of phenotypic traits, and applied statistical methods commonly used in the study of natural variants to an engineered mutant strain collection representing disruptions in 180 of the 192 ABC transporters within the bacterium Myxococcus xanthus. These strains display continuous variation in their phenotypic distributions, with a small number of "outlier" strains at both phenotypic extremes, and the majority within a confidence interval about the mean that always includes wild type. Correlation analysis reveals substantial pleiotropy, indicating that the traits do not represent independent variables. The traits measured in this study co-cluster with expression profiles, thereby demonstrating that these changes in phenotype correspond to changes at the molecular level, and therefore can be indirectly connected to changes in the genome. However, the continuous distributions, the pleiotropy, and the placement of wild type always within the confidence interval all indicate that this standard set of M. xanthus phenotypic assays is measuring a narrow range of partially overlapping traits that do not directly reflect fitness. This is likely a significant cause of the observed small phenotypic impact from mutation, and is unrelated to robustness and redundancy.}, } @article {pmid25087460, year = {2015}, author = {An, G and Kulkarni, S}, title = {An agent-based modeling framework linking inflammation and cancer using evolutionary principles: description of a generative hierarchy for the hallmarks of cancer and developing a bridge between mechanism and epidemiological data.}, journal = {Mathematical biosciences}, volume = {260}, number = {}, pages = {16-24}, pmid = {25087460}, issn = {1879-3134}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; P50GM53789/GM/NIGMS NIH HHS/United States ; P50 GM053789/GM/NIGMS NIH HHS/United States ; UL1 TR000430/TR/NCATS NIH HHS/United States ; P30DK42086/DK/NIDDK NIH HHS/United States ; }, mesh = {Black or African American/ethnology ; *Biological Evolution ; Breast Neoplasms/immunology ; Carcinogenesis/*immunology ; Female ; Humans ; Inflammation/*complications ; Neoplasms/*etiology ; Premenopause/immunology ; *Systems Biology ; }, abstract = {Inflammation plays a critical role in the development and progression of cancer, evident in multiple patient populations manifesting increased, non-resolving inflammation, such as inflammatory bowel disease, viral hepatitis and obesity. Given the complexity of both the inflammatory response and the process of oncogenesis, we utilize principles from the field of Translational Systems Biology to bridge the gap between basic mechanistic knowledge and clinical/epidemiologic data by integrating inflammation and oncogenesis within an agent-based model, the Inflammation and Cancer Agent-based Model (ICABM). The ICABM utilizes two previously published and clinically/epidemiologically validated mechanistic models to demonstrate the role of an increased inflammatory milieu on oncogenesis. Development of the ICABM required the creation of a generative hierarchy of the basic hallmarks of cancer to provide a foundation to ground the plethora of molecular and pathway components currently being studied. The ordering schema emphasizes the essential role of a fitness/selection frame shift to sub-organismal evolution as a basic property of cancer, where the generation of genetic instability as a negative effect for multicellular eukaryotic organisms represents the restoration of genetic plasticity used as an adaptive strategy by colonies of prokaryotic unicellular organisms. Simulations with the ICABM demonstrate that inflammation provides a functional environmental context that drives the shift to sub-organismal evolution, where increasingly inflammatory environments led to increasingly damaged genomes in microtumors (tumors below clinical detection size) and cancers. The flexibility of this platform readily facilitates tailoring the ICABM to specific cancers, their associated mechanisms and available epidemiological data. One clinical example of an epidemiological finding that could be investigated with this platform is the increased incidence of triple negative breast cancers in the premenopausal African-American population, which has been identified as having up-regulated of markers of inflammation. The fundamental nature of the ICABM suggests its usefulness as a base platform upon which additional molecular detail could be added as needed.}, } @article {pmid25086260, year = {2014}, author = {Zhang, R and Chen, YR and Du, HJ and Zhang, WY and Pan, HM and Xiao, T and Wu, LF}, title = {Characterization and phylogenetic identification of a species of spherical multicellular magnetotactic prokaryotes that produces both magnetite and greigite crystals.}, journal = {Research in microbiology}, volume = {165}, number = {7}, pages = {481-489}, doi = {10.1016/j.resmic.2014.07.012}, pmid = {25086260}, issn = {1769-7123}, mesh = {China ; Cluster Analysis ; *Crystallization ; Cytoplasm/ultrastructure ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Deltaproteobacteria/*classification/genetics/isolation & purification/*metabolism ; Ferrosoferric Oxide/*metabolism ; Geologic Sediments/*microbiology ; Iron/*metabolism ; Locomotion ; Microscopy, Electron, Transmission ; Molecular Sequence Data ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sulfides/*metabolism ; }, abstract = {Magnetotactic bacteria (MTB) are a group of Gram-negative bacteria synthesizing magnetic crystals that allow them aligning along magnetic field lines. They have diverse morphologies including cocci, rods, vibrio, spirilla, and multicellular magnetotactic prokaryotes (MMPs). MMPs are composed of 10-57 cells with peritrichous flagella on their outer surfaces and swim as an entire unit. Here, we describe a species of spherical MMPs isolated from intertidal sediments of Lake Yuehu (Yellow Sea, China). They were mainly found in the subsurface layer of gray-black sediments. Microscopy revealed that these spherical MMPs were 5.6 ± 0.9 μm in diameter and composed of approximately 16-32 ovoid cells with a helical arrangement and peritrichous flagellation. High-resolution transmission electron microscopy showed that the MMPs contained both bullet-shaped magnetite and irregular greigite magnetosomes that were arranged in chains or clusters. These MMPs displayed typical escape motility and negative phototaxis. The 16S rRNA genes of micromanipulation-purified spherical MMPs were cloned and sequenced. Phylogenetic analysis revealed that the MMP species was affiliated with Deltaproteobacteria and displayed >2.8% sequence divergence with respect to previously reported MMPs. This is the first phylogenetic identification of a spherical MMP that produces both magnetite and greigite magnetosomes.}, } @article {pmid25079475, year = {2014}, author = {Kolinko, S and Richter, M and Glöckner, FO and Brachmann, A and Schüler, D}, title = {Single-cell genomics reveals potential for magnetite and greigite biomineralization in an uncultivated multicellular magnetotactic prokaryote.}, journal = {Environmental microbiology reports}, volume = {6}, number = {5}, pages = {524-531}, doi = {10.1111/1758-2229.12198}, pmid = {25079475}, issn = {1758-2229}, mesh = {Bacterial Proteins/genetics/metabolism ; Deltaproteobacteria/classification/*genetics/isolation & purification/*metabolism ; Ferrosoferric Oxide/*metabolism ; *Genome, Bacterial ; Genomics ; Germany ; Iron/*metabolism ; Magnetosomes/genetics/metabolism ; Molecular Sequence Data ; Phylogeny ; Seawater/*microbiology ; Sulfides/*metabolism ; }, abstract = {For magnetic orientation, magnetotactic bacteria biosynthesize magnetosomes, which consist of membrane-enveloped magnetic nanocrystals of either magnetite (Fe3 O4) or greigite (Fe3 S4). While magnetite formation is increasingly well understood, much less is known about the genetic control of greigite biomineralization. Recently, two related yet distinct sets of magnetosome genes were discovered in a cultivated magnetotactic deltaproteobacterium capable of synthesizing either magnetite or greigite, or both minerals. This led to the conclusion that greigite and magnetite magnetosomes are synthesized by separate biomineralization pathways. Although magnetosomes of both mineral types co-occurred in uncultured multicellular magnetotactic prokaryotes (MMPs), so far only one type of magnetosome genes could be identified in the available genome data. The MMP Candidatus Magnetomorum strain HK-1 from coastal tidal sand flats of the North Sea (Germany) was analysed by a targeted single-cell approach. The draft genome assembly resulted in a size of 14.3 Mb and an estimated completeness of 95%. In addition to genomic features consistent with a sulfate-reducing lifestyle, we identified numerous genes putatively involved in magnetosome biosynthesis. Remarkably, most mam orthologues were present in two paralogous copies with highest similarity to either magnetite or greigite type magnetosome genes, supporting the ability to synthesize magnetite and greigite magnetosomes.}, } @article {pmid25078701, year = {2014}, author = {Jiang, H and Franz, CJ and Wang, D}, title = {Engineering recombinant Orsay virus directly in the metazoan host Caenorhabditis elegans.}, journal = {Journal of virology}, volume = {88}, number = {20}, pages = {11774-11781}, pmid = {25078701}, issn = {1098-5514}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Blotting, Western ; Caenorhabditis elegans/*virology ; DNA Primers ; DNA, Complementary ; Nodaviridae/*genetics/physiology ; Real-Time Polymerase Chain Reaction ; Virus Replication ; }, abstract = {The recent identification of Orsay virus, the first virus that is capable of naturally infecting Caenorhabditis elegans, provides a unique opportunity to explore host-virus interaction studies in this invaluable model organism. A key feature of this system is the robust genetic tractability of the host, C. elegans, which would ideally be complemented by the ability to genetically manipulate Orsay virus in parallel. To this end, we developed a plasmid-based reverse genetics system for Orsay virus by creating transgenic C. elegans strains harboring Orsay virus cDNAs. Both wild-type and mutant Orsay viruses, including a FLAG epitope-tagged recombinant Orsay virus, were generated by use of the reverse genetics system. This is the first plasmid-based virus reverse genetics system in the metazoan C. elegans. The Orsay virus reverse genetics we established will serve as a fundamental tool in host-virus interaction studies in the model organism C. elegans. Importance: To date, Orsay virus is the first and the only identified virus capable of naturally infecting Caenorhabditis elegans. C. elegans is a simple multicellular model organism that mimics many fundamental features of human biology and has been used to define many biological properties conserved through evolution. Thus, the Orsay virus-C. elegans infection system provides a unique opportunity to study host-virus interactions. In order to take maximal advantage of this system, the ability to genetically engineer mutant forms of Orsay virus would be highly desirable. Most efforts to engineer viruses have been done with cultured cells. Here we describe the creation of mutant viruses directly in the multicellular organism C. elegans without the use of cell culture. We engineered a virus expressing a genetically tagged protein that could be detected in C. elegans. This provides proof of concept for modifying Orsay virus, which will greatly facilitate studies in this experimental system.}, } @article {pmid25068149, year = {2014}, author = {Lahaye, É and Qin, Y and Jamme, F and Aubry, T and Sire, O}, title = {A multi-scale approach of the mechanisms underlying exopolysaccharide auto-organization in the Proteus mirabilis extracellular matrix.}, journal = {The Analyst}, volume = {139}, number = {19}, pages = {4879-4886}, doi = {10.1039/c4an00618f}, pmid = {25068149}, issn = {1364-5528}, mesh = {Extracellular Matrix/*metabolism ; Hydrogen Bonding ; Microscopy, Polarization ; Polysaccharides, Bacterial/chemistry/*metabolism ; Principal Component Analysis ; Proteus mirabilis/*metabolism ; Rheology ; *Spectrophotometry, Infrared ; Water/chemistry ; }, abstract = {For decades, the origin of the concentric ring pattern of bacterial swarming colonies has puzzled microbiologists. It was hypothesized that a periodic water activity variation originates a phase transition within the extracellular matrix water H bond network, which switches on and off the exopolysaccharide auto-organization. Both rheological and infrared spectroscopy measurements respectively performed at a molecular scale and on a currently migrating colony, have given a physical insight into the mechanisms which underlie the switch between swarming and consolidation phases. Thanks to in situ and real time infrared microspectroscopy, and thanks to the brilliance of the infrared beam at SOLEIL synchrotron, here we demonstrate that Proteus mirabilis swarming is triggered by a periodic variation of water activity at the colony edge. A dynamic behavior emerges from the global properties of the multicellular entity which relies on the ability of the bacterial cells to tune exoproduct synthesis in order to undergo sharp transitions at a given water activity threshold.}, } @article {pmid25048306, year = {2014}, author = {Li, SI and Buttery, NJ and Thompson, CR and Purugganan, MD}, title = {Sociogenomics of self vs. non-self cooperation during development of Dictyostelium discoideum.}, journal = {BMC genomics}, volume = {15}, number = {1}, pages = {616}, pmid = {25048306}, issn = {1471-2164}, support = {095643//Wellcome Trust/United Kingdom ; }, mesh = {Cell Adhesion Molecules/genetics/metabolism ; Chimera/genetics ; Cluster Analysis ; Dictyostelium/*genetics/growth & development ; Gene Expression Regulation ; Gene Regulatory Networks ; *Genes, Protozoan ; Principal Component Analysis ; Protozoan Proteins/genetics/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: Dictyostelium discoideum, a microbial model for social evolution, is known to distinguish self from non-self and show genotype-dependent behavior during chimeric development. Aside from a small number of cell-cell recognition genes, however, little is known about the genetic basis of self/non-self recognition in this species. Based on the key hypothesis that there should be differential expression of genes if D. discoideum cells were interacting with non-clone mates, we performed transcriptomic profiling study in this species during clonal vs. chimeric development. The transcriptomic profiles of D. discoideum cells in clones vs. different chimeras were compared at five different developmental stages using a customized microarray. Effects of chimerism on global transcriptional patterns associated with social interactions were observed.

RESULTS: We find 1,759 genes significantly different between chimera and clone, 1,144 genes associated significant strain differences, and 6,586 genes developmentally regulated over time. Principal component analysis showed a small amount of the transcriptional variance to chimerism-related factors (Chimerism: 0.18%, Chimerism × Timepoint: 0.03%). There are 162 genes specifically regulated under chimeric development, with continuous small differences between chimera vs. clone over development. Almost 60% of chimera-associated differential genes were differentially expressed at the 4 h aggregate stage, which corresponds to the initial transition of D. discoideum from solitary life to a multicellular phase.

CONCLUSIONS: A relatively small proportion of over-all variation in gene expression is explained by differences between chimeric and clonal development. The relatively small modifications in gene expression associated with chimerism is compatible with the high level of cooperation observed among different strains of D. discoideum; cells of distinct genetic backgrounds will co-aggregate indiscriminately and co-develop into fruiting bodies. Chimeric development may involve re-programming of the transcriptome through small modifications of the developmental genetic network, which may also indicate that response to social interaction involves many genes with individually small transcriptional effect.}, } @article {pmid25045925, year = {2014}, author = {Yang, Y and Yang, Y and Xie, X and Cai, X and Mei, X}, title = {Preparation and characterization of photo-responsive cell-penetrating peptide-mediated nanostructured lipid carrier.}, journal = {Journal of drug targeting}, volume = {22}, number = {10}, pages = {891-900}, doi = {10.3109/1061186X.2014.940589}, pmid = {25045925}, issn = {1029-2330}, mesh = {Antineoplastic Agents, Phytogenic/*administration & dosage/pharmacology ; Cell Line, Tumor ; Cell-Penetrating Peptides/*chemistry ; Drug Carriers/chemistry ; *Drug Delivery Systems ; Drug Stability ; Fibrosarcoma/drug therapy/pathology ; Humans ; Lipids/chemistry ; Nanostructures ; Paclitaxel/*administration & dosage/pharmacology ; Particle Size ; Tumor Microenvironment ; Ultraviolet Rays ; }, abstract = {Tumor-oriented nanocarrier drug delivery approaches with photo-sensitivity have been drawing considerable attention over the years. Here we described a nanostructured lipid carrier (NLC) modified with photo-responsive cell-penetrating peptides (pCPP-NLC). The conventional cell penetrating peptide (CPP)-mediated intracellular drug delivery system sometimes seemed limited due to the lack of target selectivity of the cell penetrating activity. In this study, pCPP (CKRRMK(Nvoc)WK(Nvo0c)K(Nvoc)), a photo-responsive CPP originated from the CPP (CKRRMKWKK), was endowed photo-responsiveness after masking of lysines in the sequence of CPP with photolabile-protective groups, and was introduced onto the surface of NLC. Accordingly, upon reaching the tumor tissues, pCPP-NLC enhance specific cancer cellular uptake after rapidly cleaving the photolabile-protective group, in this case, illumination in the presence of UV-light. In contrast, in circulation, the penetration was shielded. The pCPP-NLC carrying paclitaxel (PTX) prepared in this work possessed suitable physiochemical properties such as small particle size, high drug encapsulation efficiency, and good stability. The strong cellular uptake and cytotoxic activity of pCPP-NLC in HT-1080 cells verified the correlation with illumination. The remarkable penetration into HT-1080 multicellular tumor spheroids confirmed that the temporary mask of the photolabile-protective group in pCPP does not disturb the penetration ability of CPP in the tumor microenvironment with illumination. Furthermore, the triggered activation exhibited higher antitumor efficacy with the tumor spheroids compared with the non-modified NLC (N-NLC) and Taxol(®). In conclusion, the application of pCPP modifications may be an approach for the selectively targeted delivery of anti-tumor agents.}, } @article {pmid25043755, year = {2014}, author = {Lineweaver, CH and Davies, PC and Vincent, MD}, title = {Targeting cancer's weaknesses (not its strengths): Therapeutic strategies suggested by the atavistic model.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {36}, number = {9}, pages = {827-835}, pmid = {25043755}, issn = {1521-1878}, support = {U54 CA143862/CA/NCI NIH HHS/United States ; U54 CA143682/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Proliferation ; Energy Metabolism ; Humans ; Immunotherapy ; Neoplasms/immunology/pathology/*therapy ; Phenotype ; Tumor Escape ; }, abstract = {In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target-the-weakness strategy. Our most detailed example involves the immune system. The absence of adaptive immunity in immunosuppressed tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target-the-weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation.}, } @article {pmid25043003, year = {2014}, author = {Behjati, S and Huch, M and van Boxtel, R and Karthaus, W and Wedge, DC and Tamuri, AU and Martincorena, I and Petljak, M and Alexandrov, LB and Gundem, G and Tarpey, PS and Roerink, S and Blokker, J and Maddison, M and Mudie, L and Robinson, B and Nik-Zainal, S and Campbell, P and Goldman, N and van de Wetering, M and Cuppen, E and Clevers, H and Stratton, MR}, title = {Genome sequencing of normal cells reveals developmental lineages and mutational processes.}, journal = {Nature}, volume = {513}, number = {7518}, pages = {422-425}, pmid = {25043003}, issn = {1476-4687}, support = {092096//Wellcome Trust/United Kingdom ; WT100183MA/WT_/Wellcome Trust/United Kingdom ; 088340//Wellcome Trust/United Kingdom ; 098051//Wellcome Trust/United Kingdom ; 077012/Z/05/Z/WT_/Wellcome Trust/United Kingdom ; 104151//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Biological Clocks/genetics ; Cell Division ; Cell Lineage/*genetics ; Cells, Cultured ; Clone Cells/*cytology/*metabolism ; Embryo, Mammalian/cytology ; Genome/*genetics ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mutagenesis/*genetics ; Mutation/*genetics ; Mutation Rate ; Organoids/cytology/metabolism ; Phylogeny ; Sequence Analysis, DNA ; Tail/cytology ; }, abstract = {The somatic mutations present in the genome of a cell accumulate over the lifetime of a multicellular organism. These mutations can provide insights into the developmental lineage tree, the number of divisions that each cell has undergone and the mutational processes that have been operative. Here we describe whole genomes of clonal lines derived from multiple tissues of healthy mice. Using somatic base substitutions, we reconstructed the early cell divisions of each animal, demonstrating the contributions of embryonic cells to adult tissues. Differences were observed between tissues in the numbers and types of mutations accumulated by each cell, which likely reflect differences in the number of cell divisions they have undergone and varying contributions of different mutational processes. If somatic mutation rates are similar to those in mice, the results indicate that precise insights into development and mutagenesis of normal human cells will be possible.}, } @article {pmid25042404, year = {2015}, author = {Ćetković, H and Perina, D and Harcet, M and Mikoč, A and Herak Bosnar, M}, title = {Nme family of proteins--clues from simple animals.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {388}, number = {2}, pages = {133-142}, pmid = {25042404}, issn = {1432-1912}, mesh = {Animals ; Humans ; *Nucleoside-Diphosphate Kinase/genetics/metabolism ; Phylogeny ; }, abstract = {Nucleoside-diphosphate kinases (Nme/Nm23/NDPK) are evolutionarily conserved enzymes involved in many biological processes in vertebrates. The biochemical mechanisms of these processes are still largely unknown. The Nme family consists of ten members in humans of which Nme1/2 have been extensively studied in the context of carcinogenesis, especially metastasis formation. Lately, it has been proven that the majority of genes linked to human diseases were already present in species distantly related to humans. Most of cancer-related protein domains appeared during the two main evolutionary transitions-the emergence of unicellular eukaryotes and the transition to multicellular metazoans. In spite of these recent insights, current knowledge about cancer and status of cancer-related genes in simple animals is limited. One possible way of studying human diseases relies on analyzing genes/proteins that cause a certain disease by using model organism that represent the evolutionary level at which these genes have emerged. Therefore, basal metazoans are ideal model organisms for gaining a clearer picture how characteristics and functions of Nme genes changed in the transition to multicellularity and increasing complexity in animals, giving us exciting new evidence of their possible functions in potential pathological conditions in humans.}, } @article {pmid25041157, year = {2014}, author = {Thomas, F and Cosse, A and Le Panse, S and Kloareg, B and Potin, P and Leblanc, C}, title = {Kelps feature systemic defense responses: insights into the evolution of innate immunity in multicellular eukaryotes.}, journal = {The New phytologist}, volume = {204}, number = {3}, pages = {567-576}, doi = {10.1111/nph.12925}, pmid = {25041157}, issn = {1469-8137}, mesh = {Animals ; *Biological Evolution ; Feeding Behavior ; Gene Expression Regulation, Plant/*physiology ; Hydrogen Peroxide ; Immunity, Innate/*physiology ; Laminaria/enzymology/genetics/*immunology/*metabolism ; Mollusca/physiology ; Plant Leaves ; }, abstract = {Brown algae are one of the few eukaryotic lineages that have evolved complex multicellularity, together with Opisthokonts (animals, fungi) and Plantae (land plants, green and red algae). In these three lineages, biotic stresses induce similar local defense reactions. Animals and land plants also feature a systemic immune response, protecting the whole organism after an attack on one of its parts. However, the occurrence of systemic defenses has never been investigated in brown algae. We elicited selected parts of the kelp Laminaria digitata and monitored distant, nonchallenged areas of the same individual for subsequent defense reactions. A systemic reaction was detected following elicitation on a distant area, including an oxidative response, an increase in haloperoxidase activities and a stronger resistance against herbivory. Based on experiments with pharmacological inhibitors, the liberation of free fatty acids is proposed to play a key role in systemic signaling, reminiscent of what is known in land plants. This study is the first report, outside the phyla of Opisthokonts and Plantae, of an intraorganism communication leading to defense reactions. These findings indicate that systemic immunity emerged independently at least three times, as a consequence of convergent evolution in multicellular eukaryotic lineages.}, } @article {pmid25031031, year = {2014}, author = {Lerche, K and Hallmann, A}, title = {Stable nuclear transformation of Pandorina morum.}, journal = {BMC biotechnology}, volume = {14}, number = {}, pages = {65}, pmid = {25031031}, issn = {1472-6750}, mesh = {Base Sequence ; Cell Nucleus/*metabolism ; Chlorophyta/drug effects/*metabolism ; Fungal Proteins/genetics ; Genes, Reporter ; Gold/chemistry ; HSP70 Heat-Shock Proteins/genetics ; Kanamycin Kinase/genetics ; Luciferases/genetics ; Molecular Sequence Data ; Paromomycin/pharmacology ; Plasmids/metabolism ; Promoter Regions, Genetic ; Ribulose-Bisphosphate Carboxylase/genetics ; Streptomyces/enzymology ; Transformation, Genetic ; Volvox/enzymology ; }, abstract = {BACKGROUND: Volvocine green algae like Pandorina morum represent one of the most recent inventions of multicellularity diverged from their unicellular relatives. The 8-16 celled P. morum alga and its close multicellular relatives constitute a model lineage for research into cellular differentiation, morphogenesis and epithelial folding, sexual reproduction and evolution of multicellularity. Pandorina is the largest and most complex organism in the volvocine lineage that still exhibits isogamous sexual reproduction. So far, molecular-biological investigations in P. morum were constricted due to the absence of methods for transformation of this species, which is a prerequisite for introduction of reporter genes and (modified) genes of interest.

RESULTS: Stable nuclear transformation of P. morum was achieved using chimeric constructs with a selectable marker, a reporter gene, promoters and upstream and downstream flanking sequences from heterologous sources. DNA was introduced into the cells by particle bombardment with plasmid-coated gold particles. The aminoglycoside 3'-phosphotransferase VIII (aphVIII) gene of Streptomyces rimosus under control of an artificial, heterologous promoter was used as the selectable marker. The artificial promoter contained a tandem arrangement of the promoter of both the heat shock protein 70A (hsp70A) and the ribulose-1,5-bisphosphat-carboxylase/-oxygenase S3 (rbcS3) gene of Volvox carteri. Due to the expression of aphVIII, transformants gained up to 333-fold higher resistance to paromomycin in comparison to the parent wild-type strain.The heterologous luciferase (gluc) gene of Gaussia princeps, which was previously genetically engineered to match the nuclear codon usage of Chlamydomonas reinhardtii, was used as a co-transformed, unselectable reporter gene. The expression of the co-bombarded gluc gene in transformants and the induction of gluc by heat shock were demonstrated through bioluminescence assays.

CONCLUSION: Stable nuclear transformation of P. morum using the particle bombardment technique is now feasible. Functional expression of heterologous genes is achieved using heterologous flanking sequences from Volvox carteri and Chlamydomonas reinhardtii. The aphVIII gene of the actinobacterium S. rimosus can be used as a selectable marker for transformation experiments in the green alga P. morum. The gluc gene of the marine copepod G. princeps, expressed under control of heterologous promoter elements, represents a suitable reporter gene for monitoring gene expression or for other applications in P. morum.}, } @article {pmid25028340, year = {2014}, author = {Allen, JE and Sutherland, TE}, title = {Host protective roles of type 2 immunity: parasite killing and tissue repair, flip sides of the same coin.}, journal = {Seminars in immunology}, volume = {26}, number = {4}, pages = {329-340}, pmid = {25028340}, issn = {1096-3618}, support = {//Wellcome Trust/United Kingdom ; 095831//Wellcome Trust/United Kingdom ; MR/K01207X/1/MRC_/Medical Research Council/United Kingdom ; MR/J001929/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Cytokines/immunology ; Mice ; Nippostrongylus/*physiology ; Respiratory System/injuries/parasitology ; Strongylida Infections/*immunology/*parasitology ; Wound Healing ; }, abstract = {Metazoan parasites typically induce a type 2 immune response, characterized by T helper 2 (Th2) cells that produce the cytokines IL-4, IL-5 and IL-13 among others. The type 2 response is host protective, reducing the number of parasites either through direct killing in the tissues, or expulsion from the intestine. Type 2 immunity also protects the host against damage mediated by these large extracellular parasites as they migrate through the body. At the center of both the innate and adaptive type 2 immune response, is the IL-4Rα that mediates many of the key effector functions. Here we highlight the striking overlap between the molecules, cells and pathways that mediate both parasite control and tissue repair. We have proposed that adaptive Th2 immunity evolved out of our innate repair pathways to mediate both accelerated repair and parasite control in the face of continual assault from multicellular pathogens. Type 2 cytokines are involved in many aspects of mammalian physiology independent of helminth infection. Therefore understanding the evolutionary relationship between helminth killing and tissue repair should provide new insight into immune mechanisms of tissue protection in the face of physical injury.}, } @article {pmid25026440, year = {2014}, author = {Gawryluk, RM and Chisholm, KA and Pinto, DM and Gray, MW}, title = {Compositional complexity of the mitochondrial proteome of a unicellular eukaryote (Acanthamoeba castellanii, supergroup Amoebozoa) rivals that of animals, fungi, and plants.}, journal = {Journal of proteomics}, volume = {109}, number = {}, pages = {400-416}, doi = {10.1016/j.jprot.2014.07.005}, pmid = {25026440}, issn = {1876-7737}, support = {MOP-4124//Canadian Institutes of Health Research/Canada ; }, mesh = {Acanthamoeba castellanii/genetics/*metabolism ; Animals ; Computational Biology ; Fungi ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/*metabolism ; Plants ; Proteome/*metabolism ; Proteomics ; Protozoan Proteins/*metabolism ; }, abstract = {UNLABELLED: We present a combined proteomic and bioinformatic investigation of mitochondrial proteins from the amoeboid protist Acanthamoeba castellanii, the first such comprehensive investigation in a free-living member of the supergroup Amoebozoa. This protist was chosen both for its phylogenetic position (as a sister to animals and fungi) and its ecological ubiquity and physiological flexibility. We report 1033 A. castellanii mitochondrial protein sequences, 709 supported by mass spectrometry data (676 nucleus-encoded and 33 mitochondrion-encoded), including two previously unannotated mtDNA-encoded proteins, which we identify as highly divergent mitochondrial ribosomal proteins. Other notable findings include duplicate proteins for all of the enzymes of the tricarboxylic acid (TCA) cycle-which, along with the identification of a mitochondrial malate synthase-isocitrate lyase fusion protein, suggests the interesting possibility that the glyoxylate cycle operates in A. castellanii mitochondria. Additionally, the A. castellanii genome encodes an unusually high number (at least 29) of mitochondrion-targeted pentatricopeptide repeat (PPR) proteins, organellar RNA metabolism factors in other organisms. We discuss several key mitochondrial pathways, including DNA replication, transcription and translation, protein degradation, protein import and Fe-S cluster biosynthesis, highlighting similarities and differences in these pathways in other eukaryotes. In compositional and functional complexity, the mitochondrial proteome of A. castellanii rivals that of multicellular eukaryotes.

BIOLOGICAL SIGNIFICANCE: Comprehensive proteomic surveys of mitochondria have been undertaken in a limited number of predominantly multicellular eukaryotes. This phylogenetically narrow perspective constrains and biases our insights into mitochondrial function and evolution, as it neglects protists, which account for most of the evolutionary and functional diversity within eukaryotes. We report here the first comprehensive investigation of the mitochondrial proteome in a member (A. castellanii) of the eukaryotic supergroup Amoebozoa. Through a combination of tandem mass spectrometry (MS/MS) and in silico data mining, we have retrieved 1033 candidate mitochondrial protein sequences, 709 having MS support. These data were used to reconstruct the metabolic pathways and protein complexes of A. castellanii mitochondria, and were integrated with data from other characterized mitochondrial proteomes to augment our understanding of mitochondrial proteome evolution. Our results demonstrate the power of combining direct proteomic and bioinformatic approaches in the discovery of novel mitochondrial proteins, both nucleus-encoded and mitochondrion-encoded, and highlight the compositional complexity of the A. castellanii mitochondrial proteome, which rivals that of animals, fungi and plants.}, } @article {pmid25016582, year = {2014}, author = {Cheatle Jarvela, AM and Brubaker, L and Vedenko, A and Gupta, A and Armitage, BA and Bulyk, ML and Hinman, VF}, title = {Modular evolution of DNA-binding preference of a Tbrain transcription factor provides a mechanism for modifying gene regulatory networks.}, journal = {Molecular biology and evolution}, volume = {31}, number = {10}, pages = {2672-2688}, pmid = {25016582}, issn = {1537-1719}, support = {R01 HG003985/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; DNA/*metabolism ; Evolution, Molecular ; Gene Regulatory Networks ; Molecular Sequence Data ; Phylogeny ; Protein Array Analysis ; Sea Urchins/genetics/*metabolism ; Sequence Analysis, DNA ; Starfish/genetics/*metabolism ; T-Box Domain Proteins/*genetics/*metabolism ; }, abstract = {Gene regulatory networks (GRNs) describe the progression of transcriptional states that take a single-celled zygote to a multicellular organism. It is well documented that GRNs can evolve extensively through mutations to cis-regulatory modules (CRMs). Transcription factor proteins that bind these CRMs may also evolve to produce novelty. Coding changes are considered to be rarer, however, because transcription factors are multifunctional and hence are more constrained to evolve in ways that will not produce widespread detrimental effects. Recent technological advances have unearthed a surprising variation in DNA-binding abilities, such that individual transcription factors may recognize both a preferred primary motif and an additional secondary motif. This provides a source of modularity in function. Here, we demonstrate that orthologous transcription factors can also evolve a changed preference for a secondary binding motif, thereby offering an unexplored mechanism for GRN evolution. Using protein-binding microarray, surface plasmon resonance, and in vivo reporter assays, we demonstrate an important difference in DNA-binding preference between Tbrain protein orthologs in two species of echinoderms, the sea star, Patiria miniata, and the sea urchin, Strongylocentrotus purpuratus. Although both orthologs recognize the same primary motif, only the sea star Tbr also has a secondary binding motif. Our in vivo assays demonstrate that this difference may allow for greater evolutionary change in timing of regulatory control. This uncovers a layer of transcription factor binding divergence that could exist for many pairs of orthologs. We hypothesize that this divergence provides modularity that allows orthologous transcription factors to evolve novel roles in GRNs through modification of binding to secondary sites.}, } @article {pmid25016215, year = {2014}, author = {Zheng, Y and Hsu, FN and Xu, W and Xie, XJ and Ren, X and Gao, X and Ni, JQ and Ji, JY}, title = {A developmental genetic analysis of the lysine demethylase KDM2 mutations in Drosophila melanogaster.}, journal = {Mechanisms of development}, volume = {133}, number = {}, pages = {36-53}, pmid = {25016215}, issn = {1872-6356}, support = {R01 DK095013/DK/NIDDK NIH HHS/United States ; 1R01DK095013/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Chromosome Deletion ; Conserved Sequence ; DNA Transposable Elements ; Drosophila Proteins/chemistry/deficiency/*genetics ; Drosophila melanogaster/*enzymology/*genetics/growth & development ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Enzymologic ; Gene Knockout Techniques ; Genes, Insect ; Genetic Complementation Test ; Humans ; Jumonji Domain-Containing Histone Demethylases/chemistry/deficiency/*genetics ; Mutation ; Phylogeny ; Protein Structure, Tertiary ; }, abstract = {Post-translational modification of histones plays essential roles in the transcriptional regulation of genes in eukaryotes. Methylation on basic residues of histones is regulated by histone methyltransferases and histone demethylases, and misregulation of these enzymes has been linked to a range of diseases such as cancer. Histone lysine demethylase 2 (KDM2) family proteins have been shown to either promote or suppress tumorigenesis in different human malignancies. However, the roles and regulation of KDM2 in development are poorly understood, and the exact roles of KDM2 in regulating demethylation remain controversial. Since KDM2 proteins are highly conserved in multicellular animals, we analyzed the KDM2 ortholog in Drosophila. We have observed that dKDM2 is a nuclear protein and its level fluctuates during fly development. We generated three deficiency lines that disrupt the dKdm2 locus, and together with 10 transposon insertion lines within the dKdm2 locus, we characterized the developmental defects of these alleles. The alleles of dKdm2 define three phenotypic classes, and the intragenic complementation observed among these alleles and our subsequent analyses suggest that dKDM2 is not required for viability. In addition, loss of dKDM2 appears to have rather weak effects on histone H3 lysine 36 and 4 methylation (H3K36me and H3K4me) in the third instar wandering larvae, and we observed no effect on methylation of H3K9me2, H3K27me2 and H3K27me3 in dKdm2 mutants. Taken together, these genetic, molecular and biochemical analyses suggest that dKDM2 is not required for viability of flies, indicating that dKdm2 is likely redundant with other histone lysine demethylases in regulating normal development in Drosophila.}, } @article {pmid25013378, year = {2014}, author = {Dröge, J and Buczek, D and Suzuki, Y and Makałowski, W}, title = {Amoebozoa possess lineage-specific globin gene repertoires gained by individual horizontal gene transfers.}, journal = {International journal of biological sciences}, volume = {10}, number = {7}, pages = {689-701}, pmid = {25013378}, issn = {1449-2288}, mesh = {Amino Acid Sequence ; Amoebozoa/*genetics ; Evolution, Molecular ; *Gene Transfer, Horizontal ; Genes, Bacterial ; Genes, Protozoan ; Genome, Protozoan ; Globins/chemistry/*genetics ; Molecular Sequence Data ; *Phylogeny ; Sequence Alignment ; Sequence Analysis, Protein ; }, abstract = {The Amoebozoa represent a clade of unicellular amoeboid organisms that display a wide variety of lifestyles, including free-living and parasitic species. For example, the social amoeba Dictyostelium discoideum has the ability to aggregate into a multicellular fruiting body upon starvation, while the pathogenic amoeba Entamoeba histolytica is a parasite of humans. Globins are small heme proteins that are present in almost all extant organisms. Although several genomes of amoebozoan species have been sequenced, little is known about the phyletic distribution of globin genes within this phylum. Only two flavohemoglobins (FHbs) of D. discoideum have been reported and characterized previously while the genomes of Entamoeba species are apparently devoid of globin genes. We investigated eleven amoebozoan species for the presence of globin genes by genomic and phylogenetic in silico analyses. Additional FHb genes were identified in the genomes of four social amoebas and the true slime mold Physarum polycephalum. Moreover, a single-domain globin (SDFgb) of Hartmannella vermiformis, as well as two truncated hemoglobins (trHbs) of Acanthamoeba castellanii were identified. Phylogenetic evidence suggests that these globin genes were independently acquired via horizontal gene transfer from some ancestral bacteria. Furthermore, the phylogenetic tree of amoebozoan FHbs indicates that they do not share a common ancestry and that a transfer of FHbs from bacteria to amoeba occurred multiple times.}, } @article {pmid25009239, year = {2014}, author = {Price, S and Toal, S and Anandan, S}, title = {The TrpA protein of Trichodesmium erythraeum IMS101 is a non-fibril-forming collagen and a component of the outer sheath.}, journal = {Microbiology (Reading, England)}, volume = {160}, number = {Pt 10}, pages = {2148-2156}, doi = {10.1099/mic.0.079475-0}, pmid = {25009239}, issn = {1465-2080}, mesh = {Bacterial Proteins/chemistry/genetics/*metabolism ; Circular Dichroism ; Cluster Analysis ; Collagen/chemistry/genetics/*metabolism ; Cyanobacteria/genetics/*metabolism/*ultrastructure ; Membrane Proteins/chemistry/genetics/*metabolism ; Microscopy, Electron, Scanning ; Models, Molecular ; Phylogeny ; Protein Stability ; Sequence Homology, Amino Acid ; }, abstract = {Collagen molecules are structural in nature and primarily found in eukaryotic, multicellular organisms. Recently, a collagen-like protein, TrpA, was identified and characterized in the marine cyanobacterium Trichodesmium erythraeum IMS 101, and it was shown to be involved in maintaining the structural integrity of the trichomes. The TrpA protein contains one glycine interruption in the otherwise perfectly uninterrupted collagenous domain. In this study, we used phylogenetic analysis to determine that the TrpA protein sequence is most closely associated with non-fibril-forming collagen proteins. Structural modelling and circular dichroism data suggest that the glycine insertion decreases the stability of TrpA compared to uninterrupted collagen sequences. Additionally, scanning electron microscopy revealed that TrpA is expressed entirely on the surface of the trichomes, with no specific pattern of localization. These data indicate that the TrpA protein is part of the outer sheath of this organism. As such, this protein may function to promote adhesion between individual T. erythraeum trichomes, and between this organism and heterotrophic bacteria found in the same environment.}, } @article {pmid25003332, year = {2014}, author = {Geng, S and De Hoff, P and Umen, JG}, title = {Evolution of sexes from an ancestral mating-type specification pathway.}, journal = {PLoS biology}, volume = {12}, number = {7}, pages = {e1001904}, pmid = {25003332}, issn = {1545-7885}, support = {R01 GM078376/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Cell Nucleus/metabolism ; Evolution, Molecular ; Gene Expression Regulation ; Phylogeny ; Reproduction/*genetics ; Sex ; *Sex Chromosomes ; Sex Determination Processes ; Spermatogenesis/genetics ; Volvox/*genetics ; }, abstract = {Male and female sexes have evolved repeatedly in eukaryotes but the origins of dimorphic sexes and their relationship to mating types in unicellular species are not understood. Volvocine algae include isogamous species such as Chlamydomonas reinhardtii, with two equal-sized mating types, and oogamous multicellular species such as Volvox carteri with sperm-producing males and egg-producing females. Theoretical work predicts genetic linkage of a gamete cell-size regulatory gene(s) to an ancestral mating-type locus as a possible step in the evolution of dimorphic gametes, but this idea has not been tested. Here we show that, contrary to predictions, a single conserved mating locus (MT) gene in volvocine algae-MID, which encodes a RWP-RK domain transcription factor-evolved from its ancestral role in C. reinhardtii as a mating-type specifier, to become a determinant of sperm and egg development in V. carteri. Transgenic female V. carteri expressing male MID produced functional sperm packets during sexual development. Transgenic male V. carteri with RNA interference (RNAi)-mediated knockdowns of VcMID produced functional eggs, or self-fertile hermaphrodites. Post-transcriptional controls were found to regulate cell-type-limited expression and nuclear localization of VcMid protein that restricted its activity to nuclei of developing male germ cells and sperm. Crosses with sex-reversed strains uncoupled sex determination from sex chromosome identity and revealed gender-specific roles for male and female mating locus genes in sexual development, gamete fitness and reproductive success. Our data show genetic continuity between the mating-type specification and sex determination pathways of volvocine algae, and reveal evidence for gender-specific adaptations in the male and female mating locus haplotypes of Volvox. These findings will enable a deeper understanding of how a master regulator of mating-type determination in an ancestral unicellular species was reprogrammed to control sexually dimorphic gamete development in a multicellular descendant.}, } @article {pmid24999371, year = {2014}, author = {Desjardins, M and Xie, J and Gurler, H and Muralidhar, GG and Sacks, JD and Burdette, JE and Barbolina, MV}, title = {Versican regulates metastasis of epithelial ovarian carcinoma cells and spheroids.}, journal = {Journal of ovarian research}, volume = {7}, number = {}, pages = {70}, pmid = {24999371}, issn = {1757-2215}, mesh = {Animals ; Carcinoma, Ovarian Epithelial ; Cell Adhesion/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Disease Models, Animal ; Extracellular Matrix ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunophenotyping ; Mice ; Neoplasm Metastasis ; Neoplasms, Glandular and Epithelial/genetics/*metabolism/*pathology ; Ovarian Neoplasms/genetics/*metabolism/*pathology ; Peritoneal Neoplasms/genetics/pathology/secondary ; Peritoneum/metabolism/pathology ; RNA Interference ; Spheroids, Cellular ; Tumor Cells, Cultured ; Up-Regulation ; Versicans/genetics/*metabolism ; }, abstract = {BACKGROUND: Epithelial ovarian carcinoma is a deadly disease characterized by overt peritoneal metastasis. Individual cells and multicellular aggregates, or spheroids, seed these metastases, both commonly found in ascites. Mechanisms that foster spheroid attachment to the peritoneal tissues preceding formation of secondary lesions are largely unknown.

METHODS: Cell culture models of SKOV-3, OVCAR3, OVCAR4, Caov-3, IGROV-1, and A2780 were used. In this report the role of versican was examined in adhesion of EOC spheroids and cells to peritoneal mesothelial cell monolayers in vitro as well as in formation of peritoneal tumors using an in vivo xenograft mouse model.

RESULTS: The data demonstrate that versican is instrumental in facilitating cell and spheroid adhesion to the mesothelial cell monolayers, as its reduction with specific shRNAs led to decreased adhesion. Furthermore, spheroids with reduced expression of versican failed to disaggregate to complete monolayers when seeded atop monolayers of peritoneal mesothelial cells. Failure of spheroids lacking versican to disaggregate as efficiently as controls could be attributed to a reduced cell migration that was observed in the absence of versican expression. Importantly, both spheroids and cells with reduced expression of versican demonstrated significantly impaired ability to generate peritoneal tumors when injected intraperitoneally into athymic nude mice.

CONCLUSIONS: Taken together these data suggest that versican regulates the development of peritoneal metastasis originating from cells and spheroids.}, } @article {pmid24997592, year = {2014}, author = {Biryukova, I and Ye, T and Levashina, E}, title = {Transcriptome-wide analysis of microRNA expression in the malaria mosquito Anopheles gambiae.}, journal = {BMC genomics}, volume = {15}, number = {1}, pages = {557}, pmid = {24997592}, issn = {1471-2164}, mesh = {Animals ; Anopheles/*genetics/metabolism ; Base Sequence ; Chromosomes, Insect/genetics ; Cluster Analysis ; Conserved Sequence ; Female ; Gene Duplication ; Gene Expression Profiling ; Genes, Insect ; Insect Vectors/*genetics/metabolism ; MicroRNAs/*genetics/metabolism ; Multigene Family ; Postprandial Period ; Sequence Analysis, RNA ; *Transcriptome ; }, abstract = {BACKGROUND: microRNAs (miRNAs) are a highly abundant class of small noncoding regulatory RNAs that post-transcriptionally regulate gene expression in multicellular organisms. miRNAs are involved in a wide range of biological and physiological processes, including the regulation of host immune responses to microbial infections. Small-scale studies of miRNA expression in the malaria mosquito Anopheles gambiae have been reported, however no comprehensive analysis of miRNAs has been performed so far.

RESULTS: Using small RNA sequencing, we characterized de novo A. gambiae miRNA repertoire expressed in adult sugar- and blood-fed females. We provided transcriptional evidences for 123 miRNAs, including 58 newly identified miRNAs. Out of the newly described miRNAs, 19 miRNAs are homologs to known miRNAs in other insect species and 17 miRNAs share sequence similarity restricted to the seed sequence. The remaining 21 novel miRNAs displayed no obvious sequence homology with known miRNAs. Detailed bioinformatics analysis of the mature miRNAs revealed a sequence variation occurring at their 5'-end and leading to functional seed shifting in more than 5% of miRNAs. We also detected significant sequence heterogeneity at the 3'-ends of the mature miRNAs, mostly due to imprecise processing and post-transcriptional modifications. Comparative analysis of arm-switching events revealed the existence of species-specific production of dominant mature miRNAs induced by blood feeding in mosquitoes. We also identified new conserved and fragmented miRNA clusters and A. gambiae-specific miRNA gene duplication. Using miRNA expression profiling, we identified the differentially expressed miRNAs at an early time point after regular blood feeding and after infection with the rodent malaria parasite Plasmodium berghei. Significant changes were detected in the expression levels of 4 miRNAs in blood-fed mosquitoes, whereas 6 miRNAs were significantly upregulated after P. berghei infection.

CONCLUSIONS: In the current study, we performed the first systematic analysis of miRNAs in A. gambiae. We provided new insights on mature miRNA sequence diversity and functional shifts in the mosquito miRNA evolution. We identified a set of the differentially expressed miRNAs that respond to normal and infectious blood meals. The extended set of Anopheles miRNAs and their isoforms provides a basis for further experimental studies of miRNA expression patterns and biological functions in A. gambiae.}, } @article {pmid24992234, year = {2014}, author = {Ghang, W and Nowak, MA}, title = {Stochastic evolution of staying together.}, journal = {Journal of theoretical biology}, volume = {360}, number = {}, pages = {129-136}, doi = {10.1016/j.jtbi.2014.06.026}, pmid = {24992234}, issn = {1095-8541}, mesh = {*Biological Evolution ; Cell Division/*physiology ; Computer Simulation ; *Genetic Drift ; Genetics, Population ; *Models, Biological ; Mutation/genetics ; *Selection, Genetic ; Stochastic Processes ; }, abstract = {Staying together means that replicating units do not separate after reproduction, but remain attached to each other or in close proximity. Staying together is a driving force for evolution of complexity, including the evolution of multi-cellularity and eusociality. We analyze the fixation probability of a mutant that has the ability to stay together. We assume that the size of the complex affects the reproductive rate of its units and the probability of staying together. We examine the combined effect of natural selection and random drift on the emergence of staying together in a finite sized population. The number of states in the underlying stochastic process is an exponential function of population size. We develop a framework for any intensity of selection and give closed form solutions for special cases. We derive general results for the limit of weak selection.}, } @article {pmid24992231, year = {2014}, author = {Olejarz, JW and Nowak, MA}, title = {Evolution of staying together in the context of diffusible public goods.}, journal = {Journal of theoretical biology}, volume = {360}, number = {}, pages = {1-12}, doi = {10.1016/j.jtbi.2014.06.023}, pmid = {24992231}, issn = {1095-8541}, mesh = {*Biological Evolution ; Computer Simulation ; *Cooperative Behavior ; *Game Theory ; *Microbial Interactions ; *Models, Theoretical ; }, abstract = {We study the coevolution of staying together and cooperation. Staying together means that replicating units do not separate after reproduction, but remain in proximity. For example, following cell division the two daughter cells may not fully separate but stay attached to each other. Repeated cell division thereby can lead to a simple multi-cellular complex. We assume that cooperators generate a diffusible public good, which can be absorbed by any cell in the system. The production of the public good entails a cost, while the absorption leads to a benefit. Defectors produce no public good. Defectors have a selective advantage unless a mechanism for evolution of cooperation is at work. Here we explore the idea that the public good produced by a cooperating cell is absorbed by cells of the same complex with a probability that depends on the size of the complex. Larger complexes are better at absorbing the public goods produced by their own individuals. We derive analytical conditions for the evolution of staying together, thereby studying the coevolution of clustering and cooperation. If cooperators and defectors differ in their intrinsic efficiency to absorb the public good, then we find multiple stable equilibria and the possibility for coexistence between cooperators and defectors. Finally we study the implications of disadvantages that might arise if complexes become too large.}, } @article {pmid24984201, year = {2015}, author = {Kostrouchova, M and Kostrouch, Z}, title = {Nuclear receptors in nematode development: Natural experiments made by a phylum.}, journal = {Biochimica et biophysica acta}, volume = {1849}, number = {2}, pages = {224-237}, doi = {10.1016/j.bbagrm.2014.06.016}, pmid = {24984201}, issn = {0006-3002}, mesh = {Animals ; Caenorhabditis elegans/embryology/genetics ; Conserved Sequence ; *Evolution, Molecular ; Nematoda/*embryology/genetics/growth & development ; Receptors, Cytoplasmic and Nuclear/classification/*physiology ; }, abstract = {The development of complex multicellular organisms is dependent on regulatory decisions that are necessary for the establishment of specific differentiation and metabolic cellular states. Nuclear receptors (NRs) form a large family of transcription factors that play critical roles in the regulation of development and metabolism of Metazoa. Based on their DNA binding and ligand binding domains, NRs are divided into eight NR subfamilies from which representatives of six subfamilies are present in both deuterostomes and protostomes indicating their early evolutionary origin. In some nematode species, especially in Caenorhabditis, the family of NRs expanded to a large number of genes strikingly exceeding the number of NR genes in vertebrates or insects. Nematode NRs, including the multiplied Caenorhabditis genes, show clear relation to vertebrate and insect homologues belonging to six of the eight main NR subfamilies. This review summarizes advances in research of nematode NRs and their developmental functions. Nematode NRs can reveal evolutionarily conserved mechanisms that regulate specific developmental and metabolic processes as well as new regulatory adaptations. They represent the results of a large number of natural experiments with structural and functional potential of NRs for the evolution of the phylum. The conserved and divergent character of nematode NRs adds a new dimension to our understanding of the general biology of regulation by NRs. This article is part of a Special Issue entitled: Nuclear receptors in animal development.}, } @article {pmid24983513, year = {2014}, author = {Beemelmanns, C and Woznica, A and Alegado, RA and Cantley, AM and King, N and Clardy, J}, title = {Synthesis of the rosette-inducing factor RIF-1 and analogs.}, journal = {Journal of the American Chemical Society}, volume = {136}, number = {29}, pages = {10210-10213}, pmid = {24983513}, issn = {1520-5126}, support = {/HHMI/Howard Hughes Medical Institute/United States ; GM086258/GM/NIGMS NIH HHS/United States ; R01 GM099533/GM/NIGMS NIH HHS/United States ; T32 GM007127/GM/NIGMS NIH HHS/United States ; R01 GM086258/GM/NIGMS NIH HHS/United States ; GM099533/GM/NIGMS NIH HHS/United States ; }, mesh = {Alkanesulfonic Acids/*chemical synthesis/chemistry/pharmacology ; Bacteroidetes/*metabolism ; Choanoflagellata/*drug effects/growth & development/ultrastructure ; Lipids/*chemical synthesis/chemistry/pharmacology ; Molecular Structure ; *Morphogenesis ; Stereoisomerism ; }, abstract = {Studies on the origin of animal multicellularity have increasingly focused on one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta. Single cells of S. rosetta can develop into multicellular rosette-shaped colonies through a process of incomplete cytokinesis. Unexpectedly, the initiation of rosette development requires bacterially produced small molecules. Previously, our laboratories reported the planar structure and femtomolar rosette-inducing activity of one rosette-inducing small molecule, dubbed rosette-inducing factor 1 (RIF-1), produced by the Gram-negative Bacteroidetes bacterium Algoriphagus machipongonensis. RIF-1 belongs to the small and poorly explored class of sulfonolipids. Here, we report a modular total synthesis of RIF-1 stereoisomers and structural analogs. Rosette-induction assays using synthetic RIF-1 stereoisomers and naturally occurring analogs defined the absolute stereochemistry of RIF-1 and revealed a remarkably restrictive set of structural requirements for inducing rosette development.}, } @article {pmid24981559, year = {2015}, author = {Peng, G and Shi, X and Kadowaki, T}, title = {Evolution of TRP channels inferred by their classification in diverse animal species.}, journal = {Molecular phylogenetics and evolution}, volume = {84}, number = {}, pages = {145-157}, doi = {10.1016/j.ympev.2014.06.016}, pmid = {24981559}, issn = {1095-9513}, mesh = {Animals ; *Biological Evolution ; Invertebrates/genetics ; *Phylogeny ; Sequence Analysis, DNA ; Transient Receptor Potential Channels/*classification ; }, abstract = {The functions of TRP channels have primarily been characterized in model organisms within a limited evolutionary context. We thus characterize the TRP channels in choanoflagellate, sponge, Cnidaria, Lophotrochozoa, and arthropods to understand how they emerged during early evolution of animals and have changed during diversification of various species. As previously reported, five metazoan TRP subfamily members (TRPA, TRPC, TRPM, TRPML, and TRPV) were identified in choanoflagellates, demonstrating that they evolved before the emergence of multicellular animals. TRPN was identified in Hydra magnipapillata, and therefore emerged in the last common ancestor of Cnidaria-Bilateria. A novel subfamily member (TRPVL) was identified in Cnidaria and Capitella teleta, indicating that it was present in the last common ancestor of Cnidaria-Bilateria but has since been lost in most bilaterians. The characterization of arthropod TRP channels revealed that Daphnia pulex and insects have specifically expanded the TRPA subfamily, which diverged from the ancient TRPA1 channel gene. The diversity of TRPA channels except TRPA1 was detectable even within a single insect family, namely the ant lineage. The present study demonstrates the evolutionary history of TRP channel genes, which may have diverged in conjunction with the specific habitats and life histories of individual species.}, } @article {pmid24976004, year = {2014}, author = {Kennedy, P and Uller, T and Helanterä, H}, title = {Are ant supercolonies crucibles of a new major transition in evolution?.}, journal = {Journal of evolutionary biology}, volume = {27}, number = {9}, pages = {1784-1796}, doi = {10.1111/jeb.12434}, pmid = {24976004}, issn = {1420-9101}, mesh = {Animals ; *Ants ; *Behavior, Animal ; *Biological Evolution ; Genetic Fitness ; Models, Biological ; Selection, Genetic ; }, abstract = {The biological hierarchy of genes, cells, organisms and societies is a fundamental reality in the living world. This hierarchy of entities did not arise ex nihilo at the origin of life, but rather has been serially generated by a succession of critical events known as 'evolutionary transitions in individuality' (ETIs). Given the sequential nature of ETIs, it is natural to look for candidates to form the next hierarchical tier. We analyse claims that these candidates are found among 'supercolonies', ant populations in which discrete nests cooperate as part of a wider collective, in ways redolent of cells in a multicellular organism. Examining earlier empirical work and new data within the recently proposed 'Darwinian space' framework, we offer a novel analysis of the evolutionary status of supercolonies and show how certain key conditions might be satisfied in any future process transforming these collaborative networks into true Darwinian individuals.}, } @article {pmid24974231, year = {2014}, author = {Wakimoto, T and Egami, Y and Nakashima, Y and Wakimoto, Y and Mori, T and Awakawa, T and Ito, T and Kenmoku, H and Asakawa, Y and Piel, J and Abe, I}, title = {Calyculin biogenesis from a pyrophosphate protoxin produced by a sponge symbiont.}, journal = {Nature chemical biology}, volume = {10}, number = {8}, pages = {648-655}, pmid = {24974231}, issn = {1552-4469}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Diphosphates/*metabolism ; Drug Screening Assays, Antitumor ; HeLa Cells ; Humans ; Leukemia/drug therapy/pathology ; Marine Toxins ; Metagenome ; Mice ; Molecular Sequence Data ; Multigene Family ; Organophosphates/chemistry/metabolism/pharmacology ; Oxazoles/chemistry/*metabolism/pharmacology ; Phosphorylation ; Phosphotransferases/genetics/metabolism ; Phylogeny ; Polyketide Synthases/genetics ; Porifera/*microbiology/physiology ; RNA, Ribosomal, 16S ; Symbiosis ; }, abstract = {The Japanese marine sponge Discodermia calyx contains a major cytotoxic compound, calyculin A, which exhibits selective inhibition of protein phosphatases 1 and 2A. It has long been used as a chemical tool to evaluate intracellular signal transduction regulated by reversible protein phosphorylation. We describe the identification of the biosynthetic gene cluster of calyculin A by a metagenome mining approach. Single-cell analysis revealed that the gene cluster originates in the symbiont bacterium 'Candidatus Entotheonella' sp. A phosphotransferase encoded in the gene cluster deactivated calyculin A to produce a newly discovered diphosphate, which was actually the biosynthetic end product. The diphosphate had been previously overlooked because of the enzymatic dephosphorylation that occurred in response to sponge tissue disruption. Our work presents what is to our knowledge the first evidence for the biosynthetic process of calyculin A along with a notable phosphorylation-dephosphorylation mechanism to regulate toxicity, suggesting activated chemical defense in the most primitive of all multicellular animals.}, } @article {pmid24973266, year = {2015}, author = {Smith, JA and Leonardi, T and Huang, B and Iraci, N and Vega, B and Pluchino, S}, title = {Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases.}, journal = {Biogerontology}, volume = {16}, number = {2}, pages = {147-185}, pmid = {24973266}, issn = {1573-6768}, support = {260511/ERC_/European Research Council/International ; }, mesh = {Aging/*physiology ; Animals ; Brain/*metabolism ; Brain Diseases/*metabolism ; Cell Communication/*physiology ; Extracellular Vesicles/*metabolism ; Humans ; *Models, Biological ; }, abstract = {Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs-or specific EV cargoes-are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases.}, } @article {pmid24966537, year = {2014}, author = {Saad, II and Saha, SB and Thomas, G}, title = {The RAS subfamily Evolution - tracing evolution for its utmost exploitation.}, journal = {Bioinformation}, volume = {10}, number = {5}, pages = {293-298}, pmid = {24966537}, issn = {0973-2063}, abstract = {In the development of multicellularity, signaling proteins has played a very important role. Among them, RAS family is one of the most widely studied protein family. However, evolutionary analysis has been carried out mainly on super family level leaving sub family information in scanty. Thus, a subfamily evolutionary study on RAS evolutionary expansion is imperative as it will aid in better drug designing against dreadful diseases like Cancer and other developmental diseases. The present study was aimed to understand RAS evolution on both holistic as well as reductive level. All human RAS family genes and protein were subjected to BLAST tools to find orthologs and paralogs with different parameters followed by phylogenetic tree generation. Our results clearly showed that H-RAS is the most primitive RAS in higher eukaryotes and then diverged into other RAS family members due to different gene modification events. Furthermore, a site specific selection pressure analysis was carried out using SELECTON server which showed that H-RAS, M-RAS and N-RAS are evolving faster than K-RAS and R-RAS. Thus, the results ascertain a new ground to cancer biologists to exploit negatively selected K-RAS and R-RAS as potent drug targets in cancer therapeutics.}, } @article {pmid24960463, year = {2014}, author = {Cuadrat, RR and da Serra Cruz, SM and Tschoeke, DA and Silva, E and Tosta, F and Jucá, H and Jardim, R and Campos, ML and Mattoso, M and Dávila, AM}, title = {An orthology-based analysis of pathogenic protozoa impacting global health: an improved comparative genomics approach with prokaryotes and model eukaryote orthologs.}, journal = {Omics : a journal of integrative biology}, volume = {18}, number = {8}, pages = {524-538}, pmid = {24960463}, issn = {1557-8100}, mesh = {Archaea/genetics ; Bacteria/genetics ; Databases, Protein ; Entamoeba histolytica/genetics ; *Genes, Protozoan ; Genomics ; Global Health ; Humans ; Leishmania major/genetics ; Molecular Sequence Annotation ; Phylogeny ; Plasmodium falciparum/genetics ; Protozoan Proteins/*genetics ; Sequence Homology, Nucleic Acid ; Trypanosoma brucei brucei/genetics ; Trypanosoma cruzi/genetics ; }, abstract = {A key focus in 21(st) century integrative biology and drug discovery for neglected tropical and other diseases has been the use of BLAST-based computational methods for identification of orthologous groups in pathogenic organisms to discern orthologs, with a view to evaluate similarities and differences among species, and thus allow the transfer of annotation from known/curated proteins to new/non-annotated ones. We used here a profile-based sensitive methodology to identify distant homologs, coupled to the NCBI's COG (Unicellular orthologs) and KOG (Eukaryote orthologs), permitting us to perform comparative genomics analyses on five protozoan genomes. OrthoSearch was used in five protozoan proteomes showing that 3901 and 7473 orthologs can be identified by comparison with COG and KOG proteomes, respectively. The core protozoa proteome inferred was 418 Protozoa-COG orthologous groups and 704 Protozoa-KOG orthologous groups: (i) 31.58% (132/418) belongs to the category J (translation, ribosomal structure, and biogenesis), and 9.81% (41/418) to the category O (post-translational modification, protein turnover, chaperones) using COG; (ii) 21.45% (151/704) belongs to the categories J, and 13.92% (98/704) to the O using KOG. The phylogenomic analysis showed four well-supported clades for Eukarya, discriminating Multicellular [(i) human, fly, plant and worm] and Unicellular [(ii) yeast, (iii) fungi, and (iv) protozoa] species. These encouraging results attest to the usefulness of the profile-based methodology for comparative genomics to accelerate semi-automatic re-annotation, especially of the protozoan proteomes. This approach may also lend itself for applications in global health, for example, in the case of novel drug target discovery against pathogenic organisms previously considered difficult to research with traditional drug discovery tools.}, } @article {pmid24959170, year = {2014}, author = {Hernández-Hernández, V and Rueda, D and Caballero, L and Alvarez-Buylla, ER and Benítez, M}, title = {Mechanical forces as information: an integrated approach to plant and animal development.}, journal = {Frontiers in plant science}, volume = {5}, number = {}, pages = {265}, pmid = {24959170}, issn = {1664-462X}, abstract = {Mechanical forces such as tension and compression act throughout growth and development of multicellular organisms. These forces not only affect the size and shape of the cells and tissues but are capable of modifying the expression of genes and the localization of molecular components within the cell, in the plasma membrane, and in the plant cell wall. The magnitude and direction of these physical forces change with cellular and tissue properties such as elasticity. Thus, mechanical forces and the mesoscopic fields that emerge from their local action constitute important sources of positional information. Moreover, physical and biochemical processes interact in non-linear ways during tissue and organ growth in plants and animals. In this review we discuss how such mechanical forces are generated, transmitted, and sensed in these two lineages of multicellular organisms to yield long-range positional information. In order to do so we first outline a potentially common basis for studying patterning and mechanosensing that relies on the structural principle of tensegrity, and discuss how tensegral structures might arise in plants and animals. We then provide some examples of morphogenesis in which mechanical forces appear to act as positional information during development, offering a possible explanation for ubiquitous processes, such as the formation of periodic structures. Such examples, we argue, can be interpreted in terms of tensegral phenomena. Finally, we discuss the hypothesis of mechanically isotropic points as a potentially generic mechanism for the localization and maintenance of stem-cell niches in multicellular organisms. This comparative approach aims to help uncovering generic mechanisms of morphogenesis and thus reach a better understanding of the evolution and development of multicellular phenotypes, focusing on the role of physical forces in these processes.}, } @article {pmid24957622, year = {2014}, author = {Darnell, CL and Wilson, JM and Tiwari, N and Fuentes, EJ and Kirby, JR}, title = {Chemosensory regulation of a HEAT-repeat protein couples aggregation and sporulation in Myxococcus xanthus.}, journal = {Journal of bacteriology}, volume = {196}, number = {17}, pages = {3160-3168}, pmid = {24957622}, issn = {1098-5530}, support = {T32 GM008365/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Bacterial Proteins/genetics/*metabolism ; Gene Expression Regulation, Bacterial/*physiology ; Molecular Sequence Data ; Multigene Family ; Myxococcus xanthus/genetics/metabolism/*physiology ; Phylogeny ; Protein Binding ; Protein Conformation ; Spores, Bacterial/genetics/physiology ; }, abstract = {Chemosensory systems are complex, highly modified two-component systems (TCS) used by bacteria to control various biological functions ranging from motility to sporulation. Chemosensory systems and TCS both modulate phosphorelays comprised of histidine kinases and response regulators, some of which are single-domain response regulators (SD-RRs) such as CheY. In this study, we have identified and characterized the Che7 chemosensory system of Myxococcus xanthus, a common soil bacterium which displays multicellular development in response to stress. Both genetic and biochemical analyses indicate that the Che7 system regulates development via a direct interaction between the SD-RR CheY7 and a HEAT repeat domain-containing protein, Cpc7. Phosphorylation of the SD-RR affects the interaction with its target, and residues within the α4-β5-α5 fold of the REC domain govern this interaction. The identification of the Cpc7 interaction with CheY7 extends the diversity of known targets for SD-RRs in biological systems.}, } @article {pmid24954141, year = {2014}, author = {Vostarek, F and Sankova, B and Sedmera, D}, title = {Studying dynamic events in the developing myocardium.}, journal = {Progress in biophysics and molecular biology}, volume = {115}, number = {2-3}, pages = {261-269}, doi = {10.1016/j.pbiomolbio.2014.06.002}, pmid = {24954141}, issn = {1873-1732}, mesh = {Action Potentials/physiology ; Animals ; Body Surface Potential Mapping/*methods ; Calcium Signaling/*physiology ; Heart Conduction System/*embryology/*physiology ; Humans ; Myocytes, Cardiac/*physiology ; Neural Conduction/physiology ; Voltage-Sensitive Dye Imaging/*methods ; }, abstract = {Differentiation and conduction properties of the cardiomyocytes are critically dependent on physical conditioning both in vitro and in vivo. Historically, various techniques were introduced to study dynamic events such as electrical currents and changes in ionic concentrations in live cells, multicellular preparations, or entire hearts. Here we review this technological progress demonstrating how each improvement in spatial or temporal resolution provided answers to old and provoked new questions. We further demonstrate how high-speed optical mapping of voltage and calcium can uncover pacemaking potential within the outflow tract myocardium, providing a developmental explanation of ectopic beats originating from this region in the clinical settings.}, } @article {pmid24948131, year = {2014}, author = {Blair, PJ and Rhee, PL and Sanders, KM and Ward, SM}, title = {The significance of interstitial cells in neurogastroenterology.}, journal = {Journal of neurogastroenterology and motility}, volume = {20}, number = {3}, pages = {294-317}, pmid = {24948131}, issn = {2093-0879}, support = {R01 DK040569/DK/NIDDK NIH HHS/United States ; R37 DK040569/DK/NIDDK NIH HHS/United States ; R01 DK091336/DK/NIDDK NIH HHS/United States ; R01 DK057236/DK/NIDDK NIH HHS/United States ; P01 DK041315/DK/NIDDK NIH HHS/United States ; }, abstract = {Smooth muscle layers of the gastrointestinal tract consist of a heterogeneous population of cells that include enteric neurons, several classes of interstitial cells of mesenchymal origin, a variety of immune cells and smooth muscle cells (SMCs). Over the last number of years the complexity of the interactions between these cell types has begun to emerge. For example, interstitial cells, consisting of both interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor alpha-positive (PDGFRα(+)) cells generate pacemaker activity throughout the gastrointestinal (GI) tract and also transduce enteric motor nerve signals and mechanosensitivity to adjacent SMCs. ICC and PDGFRα(+) cells are electrically coupled to SMCs possibly via gap junctions forming a multicellular functional syncytium termed the SIP syncytium. Cells that make up the SIP syncytium are highly specialized containing unique receptors, ion channels and intracellular signaling pathways that regulate the excitability of GI muscles. The unique role of these cells in coordinating GI motility is evident by the altered motility patterns in animal models where interstitial cell networks are disrupted. Although considerable advances have been made in recent years on our understanding of the roles of these cells within the SIP syncytium, the full physiological functions of these cells and the consequences of their disruption in GI muscles have not been clearly defined. This review gives a synopsis of the history of interstitial cell discovery and highlights recent advances in structural, molecular expression and functional roles of these cells in the GI tract.}, } @article {pmid24935989, year = {2014}, author = {Zamer, WE and Scheiner, SM}, title = {A conceptual framework for organismal biology: linking theories, models, and data.}, journal = {Integrative and comparative biology}, volume = {54}, number = {5}, pages = {736-756}, doi = {10.1093/icb/icu075}, pmid = {24935989}, issn = {1557-7023}, mesh = {Archaea/*physiology ; *Bacterial Physiological Phenomena ; Biological Evolution ; *Biology ; Cell Physiological Phenomena ; Ecology ; Eukaryota/*physiology ; Genetic Phenomena ; *Models, Biological ; *Virus Physiological Phenomena ; }, abstract = {Implicit or subconscious theory is especially common in the biological sciences. Yet, theory plays a variety of roles in scientific inquiry. First and foremost, it determines what does and does not count as a valid or interesting question or line of inquiry. Second, theory determines the background assumptions within which inquiries are pursued. Third, theory provides linkages among disciplines. For these reasons, it is important and useful to develop explicit theories for biology. A general theory of organisms is developed, which includes 10 fundamental principles that apply to all organisms, and 6 that apply to multicellular organisms only. The value of a general theory comes from its utility to help guide the development of more specific theories and models. That process is demonstrated by examining two domains: ecoimmunology and development. For the former, a constitutive theory of ecoimmunology is presented, and used to develop a specific model that explains energetic trade-offs that may result from an immunological response of a host to a pathogen. For the latter, some of the issues involved in trying to devise a constitutive theory that covers all of development are explored, and a more narrow theory of phenotypic novelty is presented. By its very nature, little of a theory of organisms will be new. Rather, the theory presented here is a formal expression of nearly two centuries of conceptual advances and practice in research. Any theory is dynamic and subject to debate and change. Such debate will occur as part of the present, initial formulation, as the ideas presented here are refined. The very process of debating the form of the theory acts to clarify thinking. The overarching goal is to stimulate debate about the role of theory in the study of organisms, and thereby advance our understanding of them.}, } @article {pmid24934091, year = {2014}, author = {Eguale, T and Marshall, J and Molla, B and Bhatiya, A and Gebreyes, WA and Engidawork, E and Asrat, D and Gunn, JS}, title = {Association of multicellular behaviour and drug resistance in Salmonella enterica serovars isolated from animals and humans in Ethiopia.}, journal = {Journal of applied microbiology}, volume = {117}, number = {4}, pages = {961-971}, pmid = {24934091}, issn = {1365-2672}, support = {R01 AI066208/AI/NIAID NIH HHS/United States ; D43 TW008650/TW/FIC NIH HHS/United States ; 043TW008650/TW/FIC NIH HHS/United States ; R56 AI109002/AI/NIAID NIH HHS/United States ; AI066208/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Biofilms/growth & development ; Cellulose/metabolism ; Drug Resistance, Multiple, Bacterial/genetics ; Ethiopia ; Genomic Islands ; Humans ; Integrons/genetics ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Salmonella Infections/*microbiology ; Salmonella Infections, Animal/*microbiology ; Salmonella enterica/*classification/genetics/*isolation & purification/physiology ; }, abstract = {AIMS: To determine the association between multicellular behaviour, integron status and antibiotic resistance among 87 Ethiopian Salmonella enterica isolates of animal and human origin.

METHODS AND RESULTS: Isolates were characterized for their biofilm forming ability, antimicrobial susceptibility and the presence and characteristics of a class 1 integron and Salmonella genomic island 1 (SGI1). The majority of isolates grown at environmental temperatures (20°C) exhibited robust biofilm formation (72·4%) and displayed RDAR colony morphology on Congo red agar plates. The presence of a class 1 integron correlated with the extent of drug resistance and ability to exhibit multicellular behaviour.

CONCLUSIONS: Although cellulose production and RDAR morphology correlated with increased multicellular behaviour, neither was required for biofilm formation. Contrary to previous reports, colony morphology was generally consistent within a serovar. No integrons were detected in isolates deficient for multicellular behaviour, indicating a potential role of bacterial community formation in transfer of genetic elements among environmental isolates.

Infection by Salm. enterica is a major public health problem worldwide. The dominance of multidrug resistance and multicellular behaviour in Salmonella isolates of Ethiopian origin highlights a need for integrated surveillance and further detailed phenotypic and molecular studies of isolates from this region.}, } @article {pmid24927538, year = {2014}, author = {McKay, CP}, title = {Requirements and limits for life in the context of exoplanets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {35}, pages = {12628-12633}, pmid = {24927538}, issn = {1091-6490}, mesh = {Animals ; Atmosphere/chemistry ; Brachyura ; Carbon/chemistry ; *Exobiology ; Extraterrestrial Environment/*chemistry ; *Hydrothermal Vents ; Light ; *Origin of Life ; *Photosynthesis ; Solar System ; Temperature ; *Water ; }, abstract = {The requirements for life on Earth, its elemental composition, and its environmental limits provide a way to assess the habitability of exoplanets. Temperature is key both because of its influence on liquid water and because it can be directly estimated from orbital and climate models of exoplanetary systems. Life can grow and reproduce at temperatures as low as -15 °C, and as high as 122 °C. Studies of life in extreme deserts show that on a dry world, even a small amount of rain, fog, snow, and even atmospheric humidity can be adequate for photosynthetic production producing a small but detectable microbial community. Life is able to use light at levels less than 10(-5) of the solar flux at Earth. UV or ionizing radiation can be tolerated by many microorganisms at very high levels and is unlikely to be life limiting on an exoplanet. Biologically available nitrogen may limit habitability. Levels of O2 over a few percent on an exoplanet would be consistent with the presence of multicellular organisms and high levels of O2 on Earth-like worlds indicate oxygenic photosynthesis. Other factors such as pH and salinity are likely to vary and not limit life over an entire planet or moon.}, } @article {pmid24910306, year = {2014}, author = {Petralia, RS and Mattson, MP and Yao, PJ}, title = {Aging and longevity in the simplest animals and the quest for immortality.}, journal = {Ageing research reviews}, volume = {16}, number = {}, pages = {66-82}, pmid = {24910306}, issn = {1872-9649}, support = {ZIC DC000081-01//Intramural NIH HHS/United States ; }, mesh = {Age Factors ; Aging/*physiology ; Animals ; Biological Evolution ; Ciliophora/physiology ; Cnidaria/physiology ; Humans ; Hydra/physiology ; Invertebrates/*physiology ; *Longevity ; Platyhelminths/physiology ; Porifera/physiology ; Species Specificity ; Yeasts/physiology ; }, abstract = {Here we review the examples of great longevity and potential immortality in the earliest animal types and contrast and compare these to humans and other higher animals. We start by discussing aging in single-celled organisms such as yeast and ciliates, and the idea of the immortal cell clone. Then we describe how these cell clones could become organized into colonies of different cell types that lead to multicellular animal life. We survey aging and longevity in all of the basal metazoan groups including ctenophores (comb jellies), sponges, placozoans, cnidarians (hydras, jellyfish, corals and sea anemones) and myxozoans. Then we move to the simplest bilaterian animals (with a head, three body cell layers, and bilateral symmetry), the two phyla of flatworms. A key determinant of longevity and immortality in most of these simple animals is the large numbers of pluripotent stem cells that underlie the remarkable abilities of these animals to regenerate and rejuvenate themselves. Finally, we discuss briefly the evolution of the higher bilaterians and how longevity was reduced and immortality lost due to attainment of greater body complexity and cell cycle strategies that protect these complex organisms from developing tumors. We also briefly consider how the evolution of multiple aging-related mechanisms/pathways hinders our ability to understand and modify the aging process in higher organisms.}, } @article {pmid24907565, year = {2014}, author = {Blackstone, NW}, title = {sAC as a model for understanding the impact of endosymbiosis on cell signaling.}, journal = {Biochimica et biophysica acta}, volume = {1842}, number = {12 Pt B}, pages = {2548-2554}, doi = {10.1016/j.bbadis.2014.05.037}, pmid = {24907565}, issn = {0006-3002}, mesh = {Adenylyl Cyclases/*metabolism ; Biological Evolution ; Humans ; *Signal Transduction ; *Symbiosis ; }, abstract = {As signaling pathways evolve, selection for new functions guides the co-option of existing material. Major transitions in the history of life, including the evolution of eukaryotes and multicellularity, exemplify this process. These transitions provided both strong selection and a plenitude of available material for the evolution of signaling pathways. Mechanisms that evolved to mediate conflict during the evolution of eukaryotes may subsequently have been co-opted during the many independent derivations of multicellularity. The soluble adenylyl cyclase (sAC) signaling pathway illustrates this hypothesis. Class III adenylyl cyclases, which include sAC, are found in bacteria, including the α-proteobacteria. These adenylyl cyclases are the only ones present in eukaryotes but appear to be absent in archaeans. This pattern suggests that the mitochondrial endosymbiosis brought sAC signaling to eukaryotes as part of an intact module. After transfer to the proto-nuclear genome, this module was then co-opted into numerous new functions. In the evolution of eukaryotes, sAC signaling may have mediated conflicts by maintaining metabolic homeostasis. In the evolution of multicellularity, in different lineages sAC may have been co-opted into parallel tasks originally related to conflict mediation. Elucidating the history of the sAC pathway may be relatively straightforward because it is ubiquitous and linked to near universal metabolic by-products (CO2/HCO(3)(-)). Other signaling pathways (e.g., those involving STAT and VEGF) present a greater challenge but may suggest a complementary pattern. The impact of the mitochondrial endosymbiosis on cell signaling may thus have been profound. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease.}, } @article {pmid24904645, year = {2014}, author = {Lauc, G and Krištić, J and Zoldoš, V}, title = {Glycans - the third revolution in evolution.}, journal = {Frontiers in genetics}, volume = {5}, number = {}, pages = {145}, pmid = {24904645}, issn = {1664-8021}, abstract = {The development and maintenance of a complex organism composed of trillions of cells is an extremely complex task. At the molecular level every process requires a specific molecular structures to perform it, thus it is difficult to imagine how less than tenfold increase in the number of genes between simple bacteria and higher eukaryotes enabled this quantum leap in complexity. In this perspective article we present the hypothesis that the invention of glycans was the third revolution in evolution (the appearance of nucleic acids and proteins being the first two), which enabled the creation of novel molecular entities that do not require a direct genetic template. Contrary to proteins and nucleic acids, which are made from a direct DNA template, glycans are product of a complex biosynthetic pathway affected by hundreds of genetic and environmental factors. Therefore glycans enable adaptive response to environmental changes and, unlike other epiproteomic modifications, which act as off/on switches, glycosylation significantly contributes to protein structure and enables novel functions. The importance of glycosylation is evident from the fact that nearly all proteins invented after the appearance of multicellular life are composed of both polypeptide and glycan parts.}, } @article {pmid24901223, year = {2014}, author = {Kuhn, M and Hyman, AA and Beyer, A}, title = {Coiled-coil proteins facilitated the functional expansion of the centrosome.}, journal = {PLoS computational biology}, volume = {10}, number = {6}, pages = {e1003657}, pmid = {24901223}, issn = {1553-7358}, mesh = {Algorithms ; Animals ; Centrosome/chemistry/*physiology ; Computational Biology ; Fungi ; Humans ; Phylogeny ; Protein Interaction Maps/*physiology ; Proteins/*chemistry/*classification ; }, abstract = {Repurposing existing proteins for new cellular functions is recognized as a main mechanism of evolutionary innovation, but its role in organelle evolution is unclear. Here, we explore the mechanisms that led to the evolution of the centrosome, an ancestral eukaryotic organelle that expanded its functional repertoire through the course of evolution. We developed a refined sequence alignment technique that is more sensitive to coiled coil proteins, which are abundant in the centrosome. For proteins with high coiled-coil content, our algorithm identified 17% more reciprocal best hits than BLAST. Analyzing 108 eukaryotic genomes, we traced the evolutionary history of centrosome proteins. In order to assess how these proteins formed the centrosome and adopted new functions, we computationally emulated evolution by iteratively removing the most recently evolved proteins from the centrosomal protein interaction network. Coiled-coil proteins that first appeared in the animal-fungi ancestor act as scaffolds and recruit ancestral eukaryotic proteins such as kinases and phosphatases to the centrosome. This process created a signaling hub that is crucial for multicellular development. Our results demonstrate how ancient proteins can be co-opted to different cellular localizations, thereby becoming involved in novel functions.}, } @article {pmid24895293, year = {2014}, author = {Ollivaux, C and Soyez, D and Toullec, JY}, title = {Biogenesis of D-amino acid containing peptides/proteins: where, when and how?.}, journal = {Journal of peptide science : an official publication of the European Peptide Society}, volume = {20}, number = {8}, pages = {595-612}, doi = {10.1002/psc.2637}, pmid = {24895293}, issn = {1099-1387}, mesh = {Alanine Racemase/metabolism ; Amino Acids/*chemistry ; Animals ; Anura ; Peptides/*chemistry ; Protein Processing, Post-Translational ; Ranidae ; Spiders ; Stereoisomerism ; Substrate Specificity ; }, abstract = {Peptides and proteins are chiral molecules with their structure determined by the composition and configuration of the amino acids constituting them. Natural amino acids (except glycine) display two chiral types (l- and d-enantiomers). For example, the presence of octopine, a derivative of l-arginine and d-alanine in octopus, or peptidyl poly-d-glutamic acid in a bacterial cell wall was demonstrated in the 1920s and 1930s, respectively. Nevertheless, an old dogma in biology was that proteins (in a strict sense) are composed of amino acids in the l-configuration exclusively, until a d-alanyl residue was reported in a frog skin opioid peptide in the early 1980s, and since, numerous d-amino acid containing peptides (DAACPs) have been discovered in multicellular organisms. Several hypotheses may be formulated to explain the origin of a d-residue in the peptide/protein chain. It may result from different mechanisms such as incorporation of a d-amino acid, non-enzymatic racemisation associated with ageing or diseases and enzymatic posttranslational modification. In the last case, the DAACPs are synthesised via a ribosome-dependent manner, and a normal codon for l-amino acid is present in the mRNA at the position where the d-residue is processed in the mature peptide by peptidyl aminoacyl l-d isomerisation, a peculiar and subtle posttranslational modification. In this review, the different pathways of biogenesis of DAACPs not only in bacteria but also in multicellular organisms are discussed, along with the description of the cellular specificity, the enzyme specificity and the substrate specificity of peptidyl aminoacyl l-d isomerisation.}, } @article {pmid24890266, year = {2014}, author = {Storch, D and Menzel, L and Frickenhaus, S and Pörtner, HO}, title = {Climate sensitivity across marine domains of life: limits to evolutionary adaptation shape species interactions.}, journal = {Global change biology}, volume = {20}, number = {10}, pages = {3059-3067}, doi = {10.1111/gcb.12645}, pmid = {24890266}, issn = {1365-2486}, mesh = {Acclimatization/physiology ; *Adaptation, Physiological ; *Aquatic Organisms ; Archaea ; Bacteria ; *Biological Evolution ; *Climate Change ; *Ecosystem ; Eukaryota ; Hot Temperature ; Oceans and Seas ; Oxygen/metabolism ; }, abstract = {Organisms in all domains, Archaea, Bacteria, and Eukarya will respond to climate change with differential vulnerabilities resulting in shifts in species distribution, coexistence, and interactions. The identification of unifying principles of organism functioning across all domains would facilitate a cause and effect understanding of such changes and their implications for ecosystem shifts. For example, the functional specialization of all organisms in limited temperature ranges leads us to ask for unifying functional reasons. Organisms also specialize in either anoxic or various oxygen ranges, with animals and plants depending on high oxygen levels. Here, we identify thermal ranges, heat limits of growth, and critically low (hypoxic) oxygen concentrations as proxies of tolerance in a meta-analysis of data available for marine organisms, with special reference to domain-specific limits. For an explanation of the patterns and differences observed, we define and quantify a proxy for organismic complexity across species from all domains. Rising complexity causes heat (and hypoxia) tolerances to decrease from Archaea to Bacteria to uni- and then multicellular Eukarya. Within and across domains, taxon-specific tolerance limits likely reflect ultimate evolutionary limits of its species to acclimatization and adaptation. We hypothesize that rising taxon-specific complexities in structure and function constrain organisms to narrower environmental ranges. Low complexity as in Archaea and some Bacteria provide life options in extreme environments. In the warmest oceans, temperature maxima reach and will surpass the permanent limits to the existence of multicellular animals, plants and unicellular phytoplankter. Smaller, less complex unicellular Eukarya, Bacteria, and Archaea will thus benefit and predominate even more in a future, warmer, and hypoxic ocean.}, } @article {pmid24887200, year = {2014}, author = {Stewart, JE}, title = {The direction of evolution: the rise of cooperative organization.}, journal = {Bio Systems}, volume = {123}, number = {}, pages = {27-36}, doi = {10.1016/j.biosystems.2014.05.006}, pmid = {24887200}, issn = {1872-8324}, mesh = {Animals ; *Biodiversity ; *Biological Evolution ; Conservation of Energy Resources/trends ; Ecosystem ; *Environment ; Eukaryotic Cells/metabolism/physiology ; *Genetic Variation ; Humans ; Prokaryotic Cells/metabolism/physiology ; }, abstract = {Two great trends are evident in the evolution of life on Earth: towards increasing diversification and towards increasing integration. Diversification has spread living processes across the planet, progressively increasing the range of environments and free energy sources exploited by life. Integration has proceeded through a stepwise process in which living entities at one level are integrated into cooperative groups that become larger-scale entities at the next level, and so on, producing cooperative organizations of increasing scale (for example, cooperative groups of simple cells gave rise to the more complex eukaryote cells, groups of these gave rise to multi-cellular organisms, and cooperative groups of these organisms produced animal societies). The trend towards increasing integration has continued during human evolution with the progressive increase in the scale of human groups and societies. The trends towards increasing diversification and integration are both driven by selection. An understanding of the trajectory and causal drivers of the trends suggests that they are likely to culminate in the emergence of a global entity. This entity would emerge from the integration of the living processes, matter, energy and technology of the planet into a global cooperative organization. Such an integration of the results of previous diversifications would enable the global entity to exploit the widest possible range of resources across the varied circumstances of the planet. This paper demonstrates that it's case for directionality meets the tests and criticisms that have proven fatal to previous claims for directionality in evolution.}, } @article {pmid24885189, year = {2014}, author = {Ritter, A and Dittami, SM and Goulitquer, S and Correa, JA and Boyen, C and Potin, P and Tonon, T}, title = {Transcriptomic and metabolomic analysis of copper stress acclimation in Ectocarpus siliculosus highlights signaling and tolerance mechanisms in brown algae.}, journal = {BMC plant biology}, volume = {14}, number = {}, pages = {116}, pmid = {24885189}, issn = {1471-2229}, mesh = {Acclimatization/drug effects/*genetics ; Algal Proteins/metabolism ; Amino Acids/metabolism ; Chromatography, High Pressure Liquid ; Cluster Analysis ; Copper/*toxicity ; Discriminant Analysis ; Down-Regulation/drug effects/genetics ; Fatty Acids/metabolism ; Gas Chromatography-Mass Spectrometry ; Gene Expression Profiling ; Humans ; Least-Squares Analysis ; Metabolic Networks and Pathways/drug effects/genetics ; Metabolome/*drug effects/genetics ; Metabolomics ; Oxidative Stress/drug effects/genetics ; Oxylipins/metabolism ; Phaeophyta/drug effects/*genetics/*physiology ; Photosynthesis/drug effects/genetics ; Phylogeny ; Signal Transduction/drug effects/*genetics ; Stress, Physiological/drug effects/*genetics ; Transcriptome/*drug effects ; Up-Regulation/drug effects/genetics ; }, abstract = {BACKGROUND: Brown algae are sessile macro-organisms of great ecological relevance in coastal ecosystems. They evolved independently from land plants and other multicellular lineages, and therefore hold several original ontogenic and metabolic features. Most brown algae grow along the coastal zone where they face frequent environmental changes, including exposure to toxic levels of heavy metals such as copper (Cu).

RESULTS: We carried out large-scale transcriptomic and metabolomic analyses to decipher the short-term acclimation of the brown algal model E. siliculosus to Cu stress, and compared these data to results known for other abiotic stressors. This comparison demonstrates that Cu induces oxidative stress in E. siliculosus as illustrated by the transcriptomic overlap between Cu and H2O2 treatments. The common response to Cu and H2O2 consisted in the activation of the oxylipin and the repression of inositol signaling pathways, together with the regulation of genes coding for several transcription-associated proteins. Concomitantly, Cu stress specifically activated a set of genes coding for orthologs of ABC transporters, a P1B-type ATPase, ROS detoxification systems such as a vanadium-dependent bromoperoxidase, and induced an increase of free fatty acid contents. Finally we observed, as a common abiotic stress mechanism, the activation of autophagic processes on one hand and the repression of genes involved in nitrogen assimilation on the other hand.

CONCLUSIONS: Comparisons with data from green plants indicate that some processes involved in Cu and oxidative stress response are conserved across these two distant lineages. At the same time the high number of yet uncharacterized brown alga-specific genes induced in response to copper stress underlines the potential to discover new components and molecular interactions unique to these organisms. Of particular interest for future research is the potential cross-talk between reactive oxygen species (ROS)-, myo-inositol-, and oxylipin signaling.}, } @article {pmid24876391, year = {2014}, author = {Mohri, K and Hata, T and Kikuchi, H and Oshima, Y and Urushihara, H}, title = {Defects in the synthetic pathway prevent DIF-1 mediated stalk lineage specification cascade in the non-differentiating social amoeba, Acytostelium subglobosum.}, journal = {Biology open}, volume = {3}, number = {6}, pages = {553-560}, pmid = {24876391}, issn = {2046-6390}, abstract = {Separation of somatic cells from germ-line cells is a crucial event for multicellular organisms, but how this step was achieved during evolution remains elusive. In Dictyostelium discoideum and many other dictyostelid species, solitary amoebae gather and form a multicellular fruiting body in which germ-line spores and somatic stalk cells differentiate, whereas in Acytostelium subglobosum, acellular stalks form and all aggregated amoebae become spores. In this study, because most D. discoideum genes known to be required for stalk cell differentiation have homologs in A. subglobosum, we inferred functional variations in these genes and examined conservation of the stalk cell specification cascade of D. discoideum mediated by the polyketide differentiation-inducing factor-1 (DIF-1) in A. subglobosum. Through heterologous expression of A. subglobosum orthologs of DIF-1 biosynthesis genes in D. discoideum, we confirmed that two of the three genes were functional equivalents, while DIF-methyltransferase (As-dmtA) involved at the final step of DIF-1 synthesis was not. In fact, DIF-1 activity was undetectable in A. subglobosum lysates and amoebae of this species were not responsive to DIF-1, suggesting a lack of DIF-1 production in this species. On the other hand, the molecular function of an A. subglobosum ortholog of DIF-1 responsive transcription factor was equivalent with that of D. discoideum and inhibition of polyketide synthesis caused developmental arrest in A. subglobosum, which could not be rescued by DIF-1 addition. These results suggest that non-DIF-1 polyketide cascades involving downstream transcription factors are required for fruiting body development of A. subglobosum.}, } @article {pmid24875633, year = {2014}, author = {Deniaud-Bouët, E and Kervarec, N and Michel, G and Tonon, T and Kloareg, B and Hervé, C}, title = {Chemical and enzymatic fractionation of cell walls from Fucales: insights into the structure of the extracellular matrix of brown algae.}, journal = {Annals of botany}, volume = {114}, number = {6}, pages = {1203-1216}, pmid = {24875633}, issn = {1095-8290}, mesh = {Biological Evolution ; Cell Wall/*chemistry/metabolism ; Cellulose/metabolism ; Extracellular Matrix/*metabolism ; Fucose/metabolism ; Models, Structural ; Phaeophyta/*chemistry/metabolism/ultrastructure ; Polysaccharides/*metabolism ; }, abstract = {BACKGROUND AND AIMS: Brown algae are photosynthetic multicellular marine organisms evolutionarily distant from land plants, with a distinctive cell wall. They feature carbohydrates shared with plants (cellulose), animals (fucose-containing sulfated polysaccharides, FCSPs) or bacteria (alginates). How these components are organized into a three-dimensional extracellular matrix (ECM) still remains unclear. Recent molecular analysis of the corresponding biosynthetic routes points toward a complex evolutionary history that shaped the ECM structure in brown algae.

METHODS: Exhaustive sequential extractions and composition analyses of cell wall material from various brown algae of the order Fucales were performed. Dedicated enzymatic degradations were used to release and identify cell wall partners. This approach was complemented by systematic chromatographic analysis to study polymer interlinks further. An additional structural assessment of the sulfated fucan extracted from Himanthalia elongata was made.

KEY RESULTS: The data indicate that FCSPs are tightly associated with proteins and cellulose within the walls. Alginates are associated with most phenolic compounds. The sulfated fucans from H. elongata were shown to have a regular α-(1→3) backbone structure, while an alternating α-(1→3), (1→4) structure has been described in some brown algae from the order Fucales.

CONCLUSIONS: The data provide a global snapshot of the cell wall architecture in brown algae, and contribute to the understanding of the structure-function relationships of the main cell wall components. Enzymatic cross-linking of alginates by phenols may regulate the strengthening of the wall, and sulfated polysaccharides may play a key role in the adaptation to osmotic stress. The emergence and evolution of ECM components is further discussed in relation to the evolution of multicellularity in brown algae.}, } @article {pmid24870038, year = {2014}, author = {Mendes-Soares, H and Chen, IC and Fitzpatrick, K and Velicer, GJ}, title = {Chimaeric load among sympatric social bacteria increases with genotype richness.}, journal = {Proceedings. Biological sciences}, volume = {281}, number = {1787}, pages = {}, pmid = {24870038}, issn = {1471-2954}, support = {R01 GM079690/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; *Genotype ; Microbial Interactions ; Myxococcus xanthus/genetics/*physiology ; Sympatry ; }, abstract = {The total productivity of social groups can be determined by interactions among their constituents. Chimaeric load--the reduction of group productivity caused by antagonistic within-group heterogeneity--may be common in heterogeneous microbial groups due to dysfunctional behavioural interactions between distinct individuals. However, some instances of chimaerism in social microbes can increase group productivity, thus making a general relationship between chimaerism and group-level performance non-obvious. Using genetically similar strains of the soil bacterium Myxococcus xanthus that were isolated from a single centimetre-scale patch of soil, we tested for a relationship between degree of chimaerism (genotype richness) and total group performance at social behaviours displayed by this species. Within-group genotype richness was found to correlate negatively with total group performance at most traits examined, including swarming in both predatory and prey-free environments and spore production during development. These results suggest that interactions between such neighbouring strains in the wild will tend to be mutually antagonistic. Negative correlations between group performance and average genetic distance among group constituents at three known social genes were not found, suggesting that divergence at other loci that govern social interaction phenotypes is responsible for the observed chimaeric load. The potential for chimaeric load to result from co-aggregation among even closely related neighbours may promote the maintenance and strengthening of kin discrimination mechanisms, such as colony-merger incompatibilities observed in M. xanthus. The findings reported here may thus have implications for understanding the evolution and maintenance of diversity in structured populations of soil microbes.}, } @article {pmid24870021, year = {2014}, author = {Alam, T and Alazmi, M and Gao, X and Arold, ST}, title = {How to find a leucine in a haystack? Structure, ligand recognition and regulation of leucine-aspartic acid (LD) motifs.}, journal = {The Biochemical journal}, volume = {460}, number = {3}, pages = {317-329}, doi = {10.1042/BJ20140298}, pmid = {24870021}, issn = {1470-8728}, mesh = {Adaptor Proteins, Signal Transducing/physiology ; Amino Acid Motifs/*physiology ; Apoptosis Regulatory Proteins/physiology ; Aspartic Acid/*metabolism ; Cell Cycle Proteins/physiology ; Focal Adhesion Kinase 2/chemistry ; Humans ; Leucine/*metabolism ; Ligands ; Membrane Proteins/physiology ; Microfilament Proteins/metabolism ; Paxillin/chemistry ; Poly(A)-Binding Protein I/metabolism ; Protein Structure, Tertiary ; Proto-Oncogene Proteins/physiology ; Proto-Oncogene Proteins c-bcl-2/physiology ; Vinculin/physiology ; }, abstract = {LD motifs (leucine-aspartic acid motifs) are short helical protein-protein interaction motifs that have emerged as key players in connecting cell adhesion with cell motility and survival. LD motifs are required for embryogenesis, wound healing and the evolution of multicellularity. LD motifs also play roles in disease, such as in cancer metastasis or viral infection. First described in the paxillin family of scaffolding proteins, LD motifs and similar acidic LXXLL interaction motifs have been discovered in several other proteins, whereas 16 proteins have been reported to contain LDBDs (LD motif-binding domains). Collectively, structural and functional analyses have revealed a surprising multivalency in LD motif interactions and a wide diversity in LDBD architectures. In the present review, we summarize the molecular basis for function, regulation and selectivity of LD motif interactions that has emerged from more than a decade of research. This overview highlights the intricate multi-level regulation and the inherently noisy and heterogeneous nature of signalling through short protein-protein interaction motifs.}, } @article {pmid24862531, year = {2014}, author = {Yan, A and Wu, M and Zhao, Y and Zhang, A and Liu, B and Schiefelbein, J and Gan, Y}, title = {Involvement of C2H2 zinc finger proteins in the regulation of epidermal cell fate determination in Arabidopsis.}, journal = {Journal of integrative plant biology}, volume = {56}, number = {12}, pages = {1112-1117}, doi = {10.1111/jipb.12221}, pmid = {24862531}, issn = {1744-7909}, mesh = {Arabidopsis/*cytology/*metabolism ; Arabidopsis Proteins/*metabolism/physiology ; Cell Differentiation/*genetics ; Gene Expression Regulation, Plant ; Plant Roots/metabolism ; Trichomes/metabolism ; Zinc Fingers/physiology ; }, abstract = {Cell fate determination is a basic developmental process during the growth of multicellular organisms. Trichomes and root hairs of Arabidopsis are both readily accessible structures originating from the epidermal cells of the aerial tissues and roots respectively, and they serve as excellent models for understanding the molecular mechanisms controlling cell fate determination and cell morphogenesis. The regulation of trichome and root hair formation is a complex program that consists of the integration of hormonal signals with a large number of transcriptional factors, including MYB and bHLH transcriptional factors. Studies during recent years have uncovered an important role of C2H2 type zinc finger proteins in the regulation of epidermal cell fate determination. Here in this minireview we briefly summarize the involvement of C2H2 zinc finger proteins in the control of trichome and root hair formation in Arabidopsis.}, } @article {pmid24857678, year = {2014}, author = {Spurrier, RG and Speer, AL and Grant, CN and Levin, DE and Grikscheit, TC}, title = {Vitrification preserves murine and human donor cells for generation of tissue-engineered intestine.}, journal = {The Journal of surgical research}, volume = {190}, number = {2}, pages = {399-406}, doi = {10.1016/j.jss.2014.04.041}, pmid = {24857678}, issn = {1095-8673}, mesh = {Adult Stem Cells/pathology ; Animals ; Humans ; *Intestine, Small/pathology ; Mesoderm/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; *Tissue Engineering ; *Vitrification ; }, abstract = {BACKGROUND: Short bowel syndrome causes significant morbidity and mortality. Tissue-engineered intestine may serve as a viable replacement. Tissue-engineered small intestine (TESI) has previously been generated in the mouse model from donor cells that were harvested and immediately reimplanted; however, this technique may prove impossible in children who are critically ill, hemodynamically unstable, or septic. We hypothesized that organoid units (OU), multicellular clusters containing epithelium and mesenchyme, could be cryopreserved for delayed production of TESI.

METHODS: OU were isolated from <3 wk-old mouse or human ileum. OU were then cryopreserved by either standard snap freezing or vitrification. In the snap freezing protocol, OU were suspended in cryoprotectant and transferred directly to -80°C for storage. The vitrification protocol began with a stepwise increase in cryoprotectant concentration followed by liquid supercooling of the OU solution to -13°C and nucleation with a metal rod to induce vitrification. Samples were then cooled to -80°C at a controlled rate of -1°C/min and subsequently plunged into liquid nitrogen for long-term storage. OU from both groups were maintained in cryostorage for at least 72 h and thawed in a 37°C water bath. Cryoprotectant was removed with serial sucrose dilutions and OU were assessed by Trypan blue assay for post-cryopreservation viability. Via techniques previously described by our laboratory, the thawed murine or human OU were either cultured in vitro or implanted on a scaffold into the omentum of a syngeneic or irradiated Nonobese Diabetic/Severe Combined Immunodeficiency, gamma chain deficient adult mouse. The resultant TESI was analyzed by histology and immunofluorescence.

RESULTS: After cryopreservation, the viability of murine OU was significantly higher in the vitrification group (93 ± 2%, mean ± standard error of the mean) compared with standard freezing (56 ± 6%) (P < 0.001, unpaired t-test, n = 25). Human OU demonstrated similar viability after vitrification (89 ± 2%). In vitro culture of thawed OU produced expanding epithelial spheres supported by a layer of mesenchyme. TESI was successfully generated from the preserved OU. Hematoxylin and eosin staining demonstrated a mucosa composed of a simple columnar epithelium whereas immunofluorescence staining confirmed the presence of both progenitor and differentiated epithelial cells. Furthermore, beta-2-microglobulin confirmed that the human TESI epithelium originated from human cells.

CONCLUSIONS: We demonstrated improved multicellular viability after vitrification over conventional cryopreservation techniques and the first successful vitrification of murine and human OU with subsequent TESI generation. Clinical application of this method may allow for delayed autologous implantation of TESI for children in extremis.}, } @article {pmid24856210, year = {2014}, author = {Petkova, MD and Little, SC and Liu, F and Gregor, T}, title = {Maternal origins of developmental reproducibility.}, journal = {Current biology : CB}, volume = {24}, number = {11}, pages = {1283-1288}, pmid = {24856210}, issn = {1879-0445}, support = {P50 GM071508/GM/NIGMS NIH HHS/United States ; R01 GM097275/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Drosophila Proteins ; Drosophila melanogaster/*embryology/*genetics/metabolism ; Embryo, Nonmammalian/embryology/metabolism ; Embryonic Development ; Female ; Gene Dosage ; Homeodomain Proteins/*genetics/metabolism ; Oogenesis ; RNA, Messenger/genetics/metabolism ; Trans-Activators/*genetics/metabolism ; }, abstract = {Cell fate decisions during multicellular development are precisely coordinated, leading to highly reproducible macroscopic structural outcomes [1-3]. The origins of this reproducibility are found at the molecular level during the earliest stages of development when patterns of morphogen molecules emerge reproducibly [4, 5]. However, although the initial conditions for these early stages are determined by the female during oogenesis, it is unknown whether reproducibility is perpetuated from oogenesis or reacquired by the zygote. To address this issue in the early Drosophila embryo, we sought to count individual maternally deposited bicoid mRNA molecules and compare variability between embryos with previously observed fluctuations in the Bicoid protein gradient [6, 7]. Here, we develop independent methods to quantify total amounts of mRNA in individual embryos and show that mRNA counts are highly reproducible between embryos to within ~9%, matching the reproducibility of the protein gradient. Reproducibility emerges from perfectly linear feedforward processes: changing the genetic dosage in the female leads to proportional changes in both mRNA and protein numbers in the embryo. Our results indicate that the reproducibility of the morphological structures of embryos originates during oogenesis, which is when the expression of maternally provided patterning factors is precisely controlled.}, } @article {pmid24853750, year = {2014}, author = {Vulin, C and Di Meglio, JM and Lindner, AB and Daerr, A and Murray, A and Hersen, P}, title = {Growing yeast into cylindrical colonies.}, journal = {Biophysical journal}, volume = {106}, number = {10}, pages = {2214-2221}, pmid = {24853750}, issn = {1542-0086}, mesh = {Biological Transport ; Cell Proliferation/drug effects ; Culture Techniques/*methods ; Dose-Response Relationship, Drug ; Glucose/metabolism/pharmacology ; Membranes, Artificial ; Microtechnology ; Porosity ; Saccharomyces cerevisiae/cytology/drug effects/*growth & development/metabolism ; }, abstract = {Microorganisms often form complex multicellular assemblies such as biofilms and colonies. Understanding the interplay between assembly expansion, metabolic yield, and nutrient diffusion within a freely growing colony remains a challenge. Most available data on microorganisms are from planktonic cultures, due to the lack of experimental tools to control the growth of multicellular assemblies. Here, we propose a method to constrain the growth of yeast colonies into simple geometric shapes such as cylinders. To this end, we designed a simple, versatile culture system to control the location of nutrient delivery below a growing colony. Under such culture conditions, yeast colonies grow vertically and only at the locations where nutrients are delivered. Colonies increase in height at a steady growth rate that is inversely proportional to the cylinder radius. We show that the vertical growth rate of cylindrical colonies is not defined by the single-cell division rate, but rather by the colony metabolic yield. This contrasts with cells in liquid culture, in which the single-cell division rate is the only parameter that defines the population growth rate. This method also provides a direct, simple method to estimate the metabolic yield of a colony. Our study further demonstrates the importance of the shape of colonies on setting their expansion. We anticipate that our approach will be a starting point for elaborate studies of the population dynamics, evolution, and ecology of microbial colonies in complex landscapes.}, } @article {pmid24848562, year = {2014}, author = {Whittle, CA and Sun, Y and Johannesson, H}, title = {Dynamics of transcriptome evolution in the model eukaryote Neurospora.}, journal = {Journal of evolutionary biology}, volume = {27}, number = {6}, pages = {1125-1135}, doi = {10.1111/jeb.12386}, pmid = {24848562}, issn = {1420-9101}, mesh = {*Evolution, Molecular ; Gene Expression Profiling ; Genome, Fungal ; Molecular Sequence Data ; Neurospora/cytology/*genetics ; Phenotype ; Reproduction ; *Transcriptome ; }, abstract = {Mounting evidence indicates that changes in the transcriptome contribute significantly to the phenotypic differentiation of closely related species. Nonetheless, further genome-wide studies, spanning a broad range of organisms, are needed to decipher the factors driving transcriptome evolution. The model Neurospora (Ascomycota) comprises a simple system for empirically studying the evolutionary dynamics of the transcriptome. Here, we studied the evolution of gene expression in Neurospora crassa and Neurospora tetrasperma and show that patterns of transcriptome evolution are connected to genome evolution, tissue type and sexual identity (mating types, mat A and mat a) in these eukaryotes. Based on the comparisons of inter- and intraspecies expression divergence, our data reveal that rapid expression divergence is more apt to occur in sexual/female (SF) than vegetative/male (VM) tissues. In addition, interspecies gene expression and protein sequence divergence were strongly correlated for SF, but not VM, tissue. A correlation between transcriptome and protein evolution parallels findings from certain animals, but not yeast, and add support for the theory that expression evolution differs fundamentally among multicellular and unicellular eukaryotes. Finally, we found that sexual identity in these hermaphroditic Neurospora species is connected to interspecies expression divergence in a tissue-dependent manner: rapid divergence occurred for mat A- and mat a-biased genes from SF and VM tissues, respectively. Based on these findings, it is hypothesized that rapid interspecies transcriptome evolution is shifting the mating types of Neurospora towards distinct female and male phenotypes, that is, sexual dimorphism.}, } @article {pmid24840820, year = {2014}, author = {El-Guizani, T and Guibert, C and Triki, S and St-Pierre, B and Ducos, E}, title = {Identification of a human ABCC10 orthologue in Catharanthus roseus reveals a U12-type intron determinant for the N-terminal domain feature.}, journal = {Journal of genetics}, volume = {93}, number = {1}, pages = {21-33}, pmid = {24840820}, issn = {0973-7731}, mesh = {ATP-Binding Cassette Transporters/chemistry/genetics ; Amino Acid Sequence ; Base Sequence ; Catharanthus/*genetics ; DNA, Complementary/chemistry/genetics ; Expressed Sequence Tags ; Gene Expression ; Gene Order ; Genetic Loci ; Humans ; Intracellular Space/metabolism ; *Introns ; Molecular Sequence Data ; Multidrug Resistance-Associated Proteins/chemistry/*genetics ; Multigene Family ; Open Reading Frames ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; *Protein Interaction Domains and Motifs ; Protein Transport ; RNA Splice Sites ; RNA Splicing ; RNA, Small Nuclear/*genetics ; Sequence Alignment ; }, abstract = {ABC (ATP-binding cassette) transporters are members of a large superfamily of proteins that utilize ATP hydrolysis to translocate a wide range of substrates across biological membranes. In general, members of C subfamily (ABCC) are structurally characterized by an additional (N-terminal) transmembrane domain (TMD0). Phylogenetic analysis of plant ABCCs separates their protein sequences into three distinct clusters: I and II are plant specific whereas cluster III contains both human and plant ABCCs. Screening of the Plant Medicinal Genomics Resource database allowed us to identify 16 ABCCs partial sequences in Catharanthus roseus; two of which belong to the unique CrABCC1 transcript that we identified in cluster III. Genomic organization of CrABCC1 TMD0 coding sequence displays an AT-AC U12-type intron that is conserved in higher plant orthologues. We showed that CrABCC1, like its human orthologue ABCC10, produces alternative transcripts that encode protein sequences with a truncated form of TMD0 without the first transmembrane span (TM1). Subcellular localization of CrABCC1 TMD0 variants using yellow fluorescent protein fusions reveals that the TM1 is required for a correct routing of the TMD0 to the tonoplast. Finally, the specific repartition of CrABCC1 orthologues in some species suggests that this gene was lost several times during evolution and that its physiological function may, rely on a common feature of multicellular eukaryotes.}, } @article {pmid24838875, year = {2014}, author = {Yaung, SJ and Church, GM and Wang, HH}, title = {Recent progress in engineering human-associated microbiomes.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1151}, number = {}, pages = {3-25}, doi = {10.1007/978-1-4939-0554-6_1}, pmid = {24838875}, issn = {1940-6029}, support = {1DP5OD009172-01/OD/NIH HHS/United States ; }, mesh = {Animals ; Genetic Engineering/*methods ; Host-Pathogen Interactions ; Humans ; Metagenomics/methods ; *Microbiota ; Models, Animal ; Synthetic Biology/methods ; }, abstract = {Recent progress in molecular biology and genetics opens up the possibility of engineering a variety of biological systems, from single-cellular to multicellular organisms. The consortia of microbes that reside on the human body, the human-associated microbiota, are particularly interesting as targets for forward engineering and manipulation due to their relevance in health and disease. New technologies in analysis and perturbation of the human microbiota will lead to better diagnostic and therapeutic strategies against diseases of microbial origin or pathogenesis. Here, we discuss recent advances that are bringing us closer to realizing the true potential of an engineered human-associated microbial community.}, } @article {pmid24826801, year = {2014}, author = {Morgan, AD and Ness, RW and Keightley, PD and Colegrave, N}, title = {Spontaneous mutation accumulation in multiple strains of the green alga, Chlamydomonas reinhardtii.}, journal = {Evolution; international journal of organic evolution}, volume = {68}, number = {9}, pages = {2589-2602}, pmid = {24826801}, issn = {1558-5646}, support = {BB/H006109/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Chlamydomonas reinhardtii/*genetics ; *Genetic Fitness ; *Genetic Variation ; Genome, Plant ; *Mutation ; }, abstract = {Estimates of mutational parameters, such as the average fitness effect of a new mutation and the rate at which new genetic variation for fitness is created by mutation, are important for the understanding of many biological processes. However, the causes of interspecific variation in mutational parameters and the extent to which they vary within species remain largely unknown. We maintained multiple strains of the unicellular eukaryote Chlamydomonas reinhardtii, for approximately 1000 generations under relaxed selection by transferring a single cell every ~10 generations. Mean fitness of the lines tended to decline with generations of mutation accumulation whereas mutational variance increased. We did not find any evidence for differences among strains in any of the mutational parameters estimated. The overall change in mean fitness per cell division and rate of input of mutational variance per cell division were more similar to values observed in multicellular organisms than to those in other single-celled microbes. However, after taking into account differences in genome size among species, estimates from multicellular organisms and microbes, including our new estimates from C. reinhardtii, become substantially more similar. Thus, we suggest that variation in genome size is an important determinant of interspecific variation in mutational parameters.}, } @article {pmid24823688, year = {2014}, author = {Slabodnick, MM and Ruby, JG and Dunn, JG and Feldman, JL and DeRisi, JL and Marshall, WF}, title = {The kinase regulator mob1 acts as a patterning protein for stentor morphogenesis.}, journal = {PLoS biology}, volume = {12}, number = {5}, pages = {e1001861}, pmid = {24823688}, issn = {1545-7885}, support = {R01 GM090305/GM/NIGMS NIH HHS/United States ; T32 GM007810/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Cell Division ; Ciliophora/classification/*genetics/metabolism/ultrastructure ; *Gene Expression Regulation ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors/*genetics/metabolism ; Molecular Sequence Data ; Morphogenesis/*genetics ; Phylogeny ; Plants ; Protozoan Proteins/antagonists & inhibitors/*genetics/metabolism ; RNA Interference ; RNA, Small Interfering/genetics/metabolism ; Regeneration/*genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {Morphogenesis and pattern formation are vital processes in any organism, whether unicellular or multicellular. But in contrast to the developmental biology of plants and animals, the principles of morphogenesis and pattern formation in single cells remain largely unknown. Although all cells develop patterns, they are most obvious in ciliates; hence, we have turned to a classical unicellular model system, the giant ciliate Stentor coeruleus. Here we show that the RNA interference (RNAi) machinery is conserved in Stentor. Using RNAi, we identify the kinase coactivator Mob1--with conserved functions in cell division and morphogenesis from plants to humans-as an asymmetrically localized patterning protein required for global patterning during development and regeneration in Stentor. Our studies reopen the door for Stentor as a model regeneration system.}, } @article {pmid24823361, year = {2014}, author = {Goldsby, HJ and Knoester, DB and Ofria, C and Kerr, B}, title = {The evolutionary origin of somatic cells under the dirty work hypothesis.}, journal = {PLoS biology}, volume = {12}, number = {5}, pages = {e1001858}, pmid = {24823361}, issn = {1545-7885}, mesh = {Cell Differentiation ; Cell Division ; Cell Lineage/*genetics ; *Clonal Evolution ; Computer Simulation ; Germ Cells/*cytology/growth & development ; *Models, Biological ; Mutation ; }, abstract = {Reproductive division of labor is a hallmark of multicellular organisms. However, the evolutionary pressures that give rise to delineated germ and somatic cells remain unclear. Here we propose a hypothesis that the mutagenic consequences associated with performing metabolic work favor such differentiation. We present evidence in support of this hypothesis gathered using a computational form of experimental evolution. Our digital organisms begin each experiment as undifferentiated multicellular individuals, and can evolve computational functions that improve their rate of reproduction. When such functions are associated with moderate mutagenic effects, we observe the evolution of reproductive division of labor within our multicellular organisms. Specifically, a fraction of the cells remove themselves from consideration as propagules for multicellular offspring, while simultaneously performing a disproportionately large amount of mutagenic work, and are thus classified as soma. As a consequence, other cells are able to take on the role of germ, remaining quiescent and thus protecting their genetic information. We analyze the lineages of multicellular organisms that successfully differentiate and discover that they display unforeseen evolutionary trajectories: cells first exhibit developmental patterns that concentrate metabolic work into a subset of germ cells (which we call "pseudo-somatic cells") and later evolve to eliminate the reproductive potential of these cells and thus convert them to actual soma. We also demonstrate that the evolution of somatic cells enables phenotypic strategies that are otherwise not easily accessible to undifferentiated organisms, though expression of these new phenotypic traits typically includes negative side effects such as aging.}, } @article {pmid24821426, year = {2014}, author = {Chávez-Mardones, J and Gallardo-Escárate, C}, title = {Immune response of apoptosis-related cysteine peptidases from the red abalone Haliotis rufescens (HrCas8 and HrCas3): molecular characterization and transcription expression.}, journal = {Fish & shellfish immunology}, volume = {39}, number = {1}, pages = {90-98}, doi = {10.1016/j.fsi.2014.04.027}, pmid = {24821426}, issn = {1095-9947}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Caspase 3/chemistry/*genetics/metabolism ; Caspase 8/chemistry/*genetics/metabolism ; Expressed Sequence Tags ; *Gene Expression Regulation, Enzymologic ; Gills/metabolism ; Hemolymph/metabolism ; *Immunity, Innate ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; *Snails/enzymology/genetics/immunology ; Transcriptome ; Vibrio/physiology ; }, abstract = {Caspases play an important role in the different stages of programmed cell death, or apoptosis, which has been related to the immune response in multicellular organisms. The present study characterized an initiator caspase (HrCas8) and an effector caspase (HrCas3) from the red abalone Haliotis rufescens using the RACE method and qPCR analysis. HrCas8 showed a complete sequence of 2529 base pairs (bp) with an open-reading frame (ORF) of 1911 bp, a 5'UTR of 201 bp, and a 3'UTR of 417 bp. The estimated molecular mass for the 636 amino acids from HrCas8 was 71.5 kDa with an isoelectric point of 6.2. The HrCas8 sequence had two death-effector domains (DEDs) and the subunits p20 and p10, in addition to an active site characteristic of cysteine proteins. Meanwhile, the effector caspase HrCas3 showed a complete sequence of 1404 bp, a 5'UTR of 82 bp, and a 3'UTR of 574 bp. The ORF of this caspase had 747 bp that coded for 248 residues. Moreover, the predicted molecular mass of HrCas3 was 29.4 kDa; the theoretical isoelectric point was 5.70, and the sequence evidenced a conserved caspase recruitment domain (CARD). The distribution of the caspases in distinct tissues revealed that HrCas8 was principally expressed in the hemolymph, while HrCas3 had a higher expression in the gills. A basal level of expression was found for both caspases in muscle tissue. The immune response of caspases in H. rufescens was evaluated through an injection of Vibrio anguillarum. The results showed an increase in the transcription of HrCas8 post-challenge, as well as an activation of HrCas3, which together suggest the initiation of apoptosis as a response to bacterial infection in H. rufescens.}, } @article {pmid24812307, year = {2014}, author = {Kelly, AC and Busby, B and Wickner, RB}, title = {Effect of domestication on the spread of the [PIN+] prion in Saccharomyces cerevisiae.}, journal = {Genetics}, volume = {197}, number = {3}, pages = {1007-1024}, pmid = {24812307}, issn = {1943-2631}, support = {//Intramural NIH HHS/United States ; }, mesh = {Base Sequence ; Genetic Variation ; Haplotypes/genetics ; Humans ; Hyphae/growth & development ; Likelihood Functions ; Phenotype ; Phylogeny ; Prions/*genetics ; Risk Factors ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/genetics ; Spores, Fungal/physiology ; }, abstract = {Prions (infectious proteins) cause fatal neurodegenerative diseases in mammals. In the yeast Saccharomyces cerevisiae, many toxic and lethal variants of the [PSI+] and [URE3] prions have been identified in laboratory strains, although some commonly studied variants do not seem to impair cell growth. Phylogenetic analysis has revealed four major clades of S. cerevisiae that share histories of two prion proteins and largely correspond to different ecological niches of yeast. The [PIN+] prion was most prevalent in commercialized niches, infrequent among wine/vineyard strains, and not observed in ancestral isolates. As previously reported, the [PSI+] and [URE3] prions are not found in any of these strains. Patterns of heterozygosity revealed genetic mosaicism and indicated extensive outcrossing among divergent strains in commercialized environments. In contrast, ancestral isolates were all homozygous and wine/vineyard strains were closely related to each other and largely homozygous. Cellular growth patterns were highly variable within and among clades, although ancestral isolates were the most efficient sporulators and domesticated strains showed greater tendencies for flocculation. [PIN+]-infected strains had a significantly higher likelihood of polyploidy, showed a higher propensity for flocculation compared to uninfected strains, and had higher sporulation efficiencies compared to domesticated, uninfected strains. Extensive phenotypic variability among strains from different environments suggests that S. cerevisiae is a niche generalist and that most wild strains are able to switch from asexual to sexual and from unicellular to multicellular growth in response to environmental conditions. Our data suggest that outbreeding and multicellular growth patterns adapted for domesticated environments are ecological risk factors for the [PIN+] prion in wild yeast.}, } @article {pmid24800270, year = {2014}, author = {McCune, M and Shafiee, A and Forgacs, G and Kosztin, I}, title = {Predictive modeling of post bioprinting structure formation.}, journal = {Soft matter}, volume = {10}, number = {11}, pages = {1790-1800}, doi = {10.1039/c3sm52806e}, pmid = {24800270}, issn = {1744-6848}, mesh = {*Biophysics ; *Bioprinting ; *Cell Aggregation ; Computer Simulation ; Models, Biological ; Tissue Engineering ; }, abstract = {Cellular particle dynamics (CPD) is an effective computational method to describe the shape evolution and biomechanical relaxation processes in systems composed of micro tissues such as multicellular aggregates. Therefore, CPD is a useful tool to predict the outcome of postprinting structure formation in bioprinting. The predictive power of CPD has been demonstrated for multicellular systems composed of identical volume-conserving spherical and cylindrical bioink units. Experiments and computer simulations were related through an independently developed theoretical formalism based on continuum mechanics. Here we generalize the CPD formalism to (i) include non-identical bioink particles often used in specific bioprinting applications, (ii) describe the more realistic experimental situation in which during the post-printing structure formation via the fusion of spherical bioink units the volume of the system decreases, and (iii) directly connect CPD simulations to the corresponding experiments without the need of the intermediate continuum theory inherently based on simplifying assumptions.}, } @article {pmid24789824, year = {2014}, author = {Hunter, T}, title = {The genesis of tyrosine phosphorylation.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {6}, number = {5}, pages = {a020644}, pmid = {24789824}, issn = {1943-0264}, mesh = {Animals ; Computational Biology ; Humans ; Phosphorylation ; Protein Engineering ; Protein Tyrosine Phosphatases/physiology ; Protein-Tyrosine Kinases/*physiology ; Tyrosine/*metabolism ; }, abstract = {Tyrosine phosphorylation of proteins was discovered in 1979, but this posttranslational modification had been "invented" by evolution more than a billion years ago in single-celled eukaryotic organisms that were the antecedents of the first multicellular animals. Because sophisticated cell-cell communication is a sine qua non for the existence of multicellular organisms, the development of cell-surface receptor systems that use tyrosine phosphorylation for transmembrane signal transduction and intracellular signaling seems likely to have been a crucial event in the evolution of metazoans. Like all types of protein phosphorylation, tyrosine phosphorylation serves to regulate proteins in multiple ways, including causing electrostatic repulsion and inducing allosteric transitions, but the most important function of phosphotyrosine (P.Tyr) is to serve as a docking site that promotes a specific interaction between a tyrosine phosphorylated protein and another protein that contains a P.Tyr-binding domain, such as an SH2 or PTB domain. Such docking interactions are essential for signal transduction downstream from receptor tyrosine kinases (RTKs) on the cell surface, which are activated on binding a cognate extracellular ligand, and, as a consequence, elicit specific cellular outcomes.}, } @article {pmid24786278, year = {2014}, author = {Heger, P and Wiehe, T}, title = {New tools in the box: an evolutionary synopsis of chromatin insulators.}, journal = {Trends in genetics : TIG}, volume = {30}, number = {5}, pages = {161-171}, doi = {10.1016/j.tig.2014.03.004}, pmid = {24786278}, issn = {0168-9525}, mesh = {Animals ; Binding Sites/genetics ; Chromatin/*genetics ; DNA-Binding Proteins/metabolism ; Enhancer Elements, Genetic ; *Evolution, Molecular ; Humans ; Insulator Elements/*genetics ; }, abstract = {Despite progress in understanding genome organization and gene expression during the last decade, the evolutionary pathways that led to the intricate patterns of gene expression in different cells of an organism are still poorly understood. Important steps in this regulation take place at the level of chromatin, where the (epi)genomic environment of a gene determines its expression in time and space. Although the basic mechanisms of gene expression apply to all eukaryotes, multicellular organisms face the additional challenge of coordinating gene expression during development. In this review we summarize and put into evolutionary context current knowledge about chromatin insulators, an important class of regulatory factors mediating these tasks. Our interpretation of historical and recent findings points to a dynamic and ongoing evolution of insulator proteins characterized by multiple instances of convergent evolution, gene loss, and binding site changes in different organisms. The idea of two autonomously evolving insulator functions (as a barrier element and an enhancer blocker) further suggests that the evolution of metazoans and their enhancer-rich gene regulatory repertoire might be connected to the radiation of enhancer blocking insulators. Although speculative at the moment, such coevolution might create tools for complex gene regulation and therefore influence the evolutionary roadmaps of metazoans.}, } @article {pmid24781500, year = {2014}, author = {Birarda, G and Bedolla, DE and Mitri, E and Pacor, S and Grenci, G and Vaccari, L}, title = {Apoptotic pathways of U937 leukemic monocytes investigated by infrared microspectroscopy and flow cytometry.}, journal = {The Analyst}, volume = {139}, number = {12}, pages = {3097-3106}, doi = {10.1039/c4an00317a}, pmid = {24781500}, issn = {1364-5528}, mesh = {*Apoptosis ; Flow Cytometry/*methods ; Humans ; Leukemia/*pathology ; Monocytes/*pathology ; Spectrophotometry, Infrared/*methods ; U937 Cells ; }, abstract = {Apoptosis is a strictly regulated cell death mechanism that plays a pivotal role in the normal evolution of multicellular organisms. Its misregulation has been associated with many diseases, making its early and reliable detection a key point for modern cellular biology. In this paper, we propose the use of infrared microspectroscopy (IRMS) as a label-free methodology for the detection of apoptotic-related biochemical processes induced on U937 leukemic monocytes by serum starvation and CCCP-exposure. The spectroscopic results are in agreement with parallel Flow Cytometry (FC) experiments, where plasma membrane integrity and mitochondrial activity were assessed. Spectroscopic outcomes complement FC data and allow drawing a more complete picture of the apoptotic pathways. In particular, we established that the two apoptosis-inducing treatments, cell starvation and CCCP exposure, affect the cell cycle in a different way. With the former, cell death is preceded by a cell cycle arrest, whereas the latter causes an increased cell cycle progression. Spectral data demonstrate that for both conditions apoptosis proceeds through the accumulation of lipid droplets within cells. Moreover, we were able to establish a spectral marker for DNA condensation/fragmentation: the enhancement of the PhI band component centred at ~1206 cm(-1), which is more sensitive than the relative intensity of the PhII band to which phospholipids and carbohydrates also contribute significantly. In conclusion, we demonstrate that the intrinsic multi-parametric nature of IRMS and its application on cells under physiological conditions can be well exploited for the investigation of apoptotic pathways.}, } @article {pmid24766896, year = {2014}, author = {Reddick, LE and Alto, NM}, title = {Bacteria fighting back: how pathogens target and subvert the host innate immune system.}, journal = {Molecular cell}, volume = {54}, number = {2}, pages = {321-328}, pmid = {24766896}, issn = {1097-4164}, support = {R01GM100486/GM/NIGMS NIH HHS/United States ; 1F32AI098384/AI/NIAID NIH HHS/United States ; R01 GM100486/GM/NIGMS NIH HHS/United States ; R01AI083359/AI/NIAID NIH HHS/United States ; R01 AI083359/AI/NIAID NIH HHS/United States ; F32 AI098384/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*immunology ; Host-Pathogen Interactions ; *Immune Evasion ; *Immunity, Innate ; *Models, Immunological ; Receptors, Pattern Recognition/physiology ; Signal Transduction/immunology ; Toll-Like Receptor 4/metabolism/physiology ; }, abstract = {The innate immune system has evolved under selective pressure since the radiation of multicellular life approximately 600 million years ago. Because of this long history, innate immune mechanisms found in modern eukaryotic organisms today are highly complex but yet built from common molecular strategies. It is now clear that evolution has selected a conserved set of antimicrobial peptides as well as pattern-recognition receptors (PRRs) that initiate cellular-based signals as a first line of defense against invading pathogens. Conversely, microbial pathogens employ their own strategies in order to evade, inhibit, or otherwise manipulate the innate immune response. Here, we discuss recent discoveries that have changed our view of immune modulatory mechanisms employed by bacterial pathogens, focusing specifically on the initial sites of microbial recognition and extending to host cellular signal transduction, proinflammatory cytokine production, and alteration of protein trafficking and secretion.}, } @article {pmid24766052, year = {2016}, author = {Qin, X}, title = {Chronic pulmonary pseudomonal infection in patients with cystic fibrosis: A model for early phase symbiotic evolution.}, journal = {Critical reviews in microbiology}, volume = {42}, number = {1}, pages = {144-157}, doi = {10.3109/1040841X.2014.907235}, pmid = {24766052}, issn = {1549-7828}, mesh = {Adaptation, Physiological ; Amino Acids/biosynthesis ; Animals ; Chronic Disease ; Coinfection ; Cystic Fibrosis/*complications ; Disease Susceptibility ; Host-Pathogen Interactions ; Humans ; Pneumonia, Bacterial/drug therapy/*etiology/*metabolism/microbiology ; Pseudomonas Infections/drug therapy/*etiology/*metabolism/microbiology ; Pseudomonas aeruginosa/physiology ; Quorum Sensing ; Symbiosis ; Virulence ; }, abstract = {Gain of "antimicrobial resistance" and "adaptive virulence" has been the dominant view of Pseudomonas aeruginosa (Pa) in cystic fibrosis (CF) in the progressively damaged host airway over the course of this chronic infection. However, the pathogenic effects of CF airway-adapted Pa strains are notably reduced. We propose that CF Pa and other bacterial cohabitants undergo host adaptation which resembles the changes found in bacterial symbionts in animal hosts. Development of clonally selected and intraspecific isogenic Pa strains which display divergent colony morphology, growth rate, auxotrophy, and antibiotic susceptibility in vitro suggests an adaptive sequence of infective exploitation-parasitism-symbiotic evolution driven by host defenses. Most importantly, the emergence of CF pseudomonal auxotrophy is frequently associated with a few specific amino acids. The selective retention or loss of specific amino acid biosynthesis in CF-adapted Pa reflects bacterium-host symbiosis and coevolution during chronic infection, not nutrient availability. This principle also argues against the long-standing concept of dietary availability leading to evolution of essential amino acid requirements in humans. A novel model of pseudomonal adaptation through multicellular bacterial syntrophy is proposed to explain early events in bacterial gene decay and decreased (not increased) virulence due to symbiotic response to host defense.}, } @article {pmid24736157, year = {2014}, author = {De Monte, S and Rainey, PB}, title = {Nascent multicellular life and the emergence of individuality.}, journal = {Journal of biosciences}, volume = {39}, number = {2}, pages = {237-248}, pmid = {24736157}, issn = {0973-7138}, mesh = {*Biological Evolution ; Humans ; Microbial Interactions ; Models, Biological ; Population Dynamics ; Selection, Genetic ; }, abstract = {The evolution of multicellular organisms from unicellular ancestors involves a shift in the level at which selection operates. It is usual to think about this shift in terms of the emergence of traits that cause heritable differences in reproductive output at the level of nascent collectives. Defining these traits and the causes of their origin lies at the heart of understanding the evolution of multicellular life. In working toward a mechanistic, take-nothing-for-granted account, we begin by recognizing that the standard Lewontin formulation of properties necessary and sufficient for evolution by natural selection does not necessarily encompass Darwinian evolution in primitive collectives where parent-offspring relationships may have been poorly defined. This, we suggest, limits the ability to conceptualize and capture the earliest manifestations of Darwinian properties. By way of solution we propose a relaxed interpretation of Lewontin's conditions and present these in the form of a set of necessary requirements for evolution by natural selection based upon the establishment of genealogical connections between recurrences of collectives. With emphasis on genealogy - as opposed to reproduction - it is possible to conceive selection acting on collectives prior to any manifestation of heritable variance in fitness. Such possibility draws attention to the evolutionary emergence of traits that strengthen causal relationships between recurrences - traits likely to underpin the emergence of forms of multiplication that establish parent-offspring relationships. Application of this framework to collectives of marginal status, particularly those whose recurrence is not defined by genealogy, makes clear that change at the level of collectives need not arise from selection acting at the higher level. We conclude by outlining applicability of our framework to loosely defined collectives of cells, such as those comprising the slugs of social amoeba and microbes that constitute the human microbiome.}, } @article {pmid24730764, year = {2014}, author = {Bull, L}, title = {Evolving functional and structural dynamism in coupled Boolean networks.}, journal = {Artificial life}, volume = {20}, number = {4}, pages = {441-455}, doi = {10.1162/ARTL_a_00137}, pmid = {24730764}, issn = {1064-5462}, mesh = {Biological Evolution ; DNA Transposable Elements/*physiology ; *Gene Regulatory Networks ; *Models, Theoretical ; Nucleic Acid Hybridization ; Transcription, Genetic ; }, abstract = {This article uses a recently presented abstract, tunable Boolean regulatory network model to further explore aspects of mobile DNA, such as transposons. The significant role of mobile DNA in the evolution of natural systems is becoming increasingly clear. This article shows how dynamically controlling network node connectivity and function via transposon-inspired mechanisms can be selected for to significant degrees under coupled regulatory network scenarios, including when such changes are heritable. Simple multicellular and coevolutionary versions of the model are considered.}, } @article {pmid24730763, year = {2014}, author = {Cussat-Blanc, S and Pollack, J}, title = {Cracking the egg: virtual embryogenesis of real robots.}, journal = {Artificial life}, volume = {20}, number = {3}, pages = {361-383}, doi = {10.1162/ARTL_a_00136}, pmid = {24730763}, issn = {1064-5462}, mesh = {Artificial Intelligence ; *Embryonic Development ; *Robotics ; }, abstract = {All multicellular living beings are created from a single cell. A developmental process, called embryogenesis, takes this first fertilized cell down a complex path of reproduction, migration, and specialization into a complex organism adapted to its environment. In most cases, the first steps of the embryogenesis take place in a protected environment such as in an egg or in utero. Starting from this observation, we propose a new approach to the generation of real robots, strongly inspired by living systems. Our robots are composed of tens of specialized cells, grown from a single cell using a bio-inspired virtual developmental process. Virtual cells, controlled by gene regulatory networks, divide, migrate, and specialize to produce the robot's body plan (morphology), and then the robot is manually built from this plan. Because the robot is as easy to assemble as Lego, the building process could be easily automated.}, } @article {pmid24728646, year = {2014}, author = {Zhang, H and Koblížková, A and Wang, K and Gong, Z and Oliveira, L and Torres, GA and Wu, Y and Zhang, W and Novák, P and Buell, CR and Macas, J and Jiang, J}, title = {Boom-Bust Turnovers of Megabase-Sized Centromeric DNA in Solanum Species: Rapid Evolution of DNA Sequences Associated with Centromeres.}, journal = {The Plant cell}, volume = {26}, number = {4}, pages = {1436-1447}, pmid = {24728646}, issn = {1532-298X}, abstract = {Centromeres are composed of long arrays of satellite repeats in most multicellular eukaryotes investigated to date. The satellite repeat-based centromeres are believed to have evolved from "neocentromeres" that originally contained only single- or low-copy sequences. However, the emergence and evolution of the satellite repeats in centromeres has been elusive. Potato (Solanum tuberosum) provides a model system for studying centromere evolution because each of its 12 centromeres contains distinct DNA sequences, allowing comparative analysis of homoeologous centromeres from related species. We conducted genome-wide analysis of the centromeric sequences in Solanum verrucosum, a wild species closely related to potato. Unambiguous homoeologous centromeric sequences were detected in only a single centromere (Cen9) between the two species. Four centromeres (Cen2, Cen4, Cen7, and Cen10) in S. verrucosum contained distinct satellite repeats that were amplified from retrotransposon-related sequences. Strikingly, the same four centromeres in potato contain either different satellite repeats (Cen2 and Cen7) or exclusively single- and low-copy sequences (Cen4 and Cen10). Our sequence comparison of five homoeologous centromeres in two Solanum species reveals rapid divergence of centromeric sequences among closely related species. We propose that centromeric satellite repeats undergo boom-bust cycles before a favorable repeat is fixed in the population.}, } @article {pmid24727478, year = {2014}, author = {Bezsonova, I}, title = {Solution NMR structure of the DNA-binding domain from Scml2 (sex comb on midleg-like 2).}, journal = {The Journal of biological chemistry}, volume = {289}, number = {22}, pages = {15739-15749}, pmid = {24727478}, issn = {1083-351X}, mesh = {Amino Acid Sequence ; Cell Cycle Proteins/chemistry/genetics/metabolism ; DNA-Binding Proteins/*chemistry/*genetics/metabolism ; *Epigenesis, Genetic ; Evolution, Molecular ; Gene Silencing ; Humans ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Phylogeny ; Polycomb-Group Proteins/*chemistry/*genetics/metabolism ; Protein Folding ; Protein Structure, Tertiary ; }, abstract = {Scml2 is a member of the Polycomb group of proteins involved in epigenetic gene silencing. Human Scml2 is a part of a multisubunit protein complex, PRC1 (Polycomb repressive complex 1), which is responsible for maintenance of gene repression, prevention of chromatin remodeling, preservation of the "stemness" of the cell, and cell differentiation. Although the majority of PRC1 subunits have been recently characterized, the structure of Scml2 and its role in PRC1-mediated gene silencing remain unknown. In this work a conserved protein domain within human Scml2 has been identified, and its structure was determined by solution NMR spectroscopy. This module was named Scm-like embedded domain, or SLED. Evolutionarily, the SLED domain emerges in the first multicellular organisms, consistent with the role of Scml2 in cell differentiation. Furthermore, it is exclusively found within the Scm-like family of proteins, often accompanied by malignant brain tumor domain (MBT) and sterile α motif (SAM) domains. The domain adopts a novel α/β fold with no structural analogues found in the Protein Data Bank (PDB). The ability of the SLED to bind double-stranded DNA was also examined, and the isolated domain was shown to interact with DNA in a sequence-specific manner. Because PRC1 complexes localize to the promoters of a specific subset of developmental genes in vivo, the SLED domain of Scml2 may provide an important link connecting the PRC1 complexes to their target genes.}, } @article {pmid24725306, year = {2015}, author = {Chen, YR and Zhang, R and Du, HJ and Pan, HM and Zhang, WY and Zhou, K and Li, JH and Xiao, T and Wu, LF}, title = {A novel species of ellipsoidal multicellular magnetotactic prokaryotes from Lake Yuehu in China.}, journal = {Environmental microbiology}, volume = {17}, number = {3}, pages = {637-647}, doi = {10.1111/1462-2920.12480}, pmid = {24725306}, issn = {1462-2920}, mesh = {Base Sequence ; China ; Deltaproteobacteria/*classification/genetics ; Ferrosoferric Oxide ; Genes, rRNA/genetics ; Iron ; Lakes/*microbiology ; Magnetosomes/*physiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sulfides ; }, abstract = {Two morphotypes of multicellular magnetotactic prokaryotes (MMPs) have been identified: spherical (several species) and ellipsoidal (previously one species). Here, we report novel ellipsoidal MMPs that are ∼ 10 × 8 μm in size, and composed of about 86 cells arranged in six to eight interlaced circles. Each MMP was composed of cells that synthesized either bullet-shaped magnetite magnetosomes alone, or both bullet-shaped magnetite and rectangular greigite magnetosomes. They showed north-seeking magnetotaxis, ping-pong motility and negative phototaxis at a velocity up to 300 μm s(-1) . During reproduction, they divided along either their long- or short-body axes. For genetic analysis, we sorted the ellipsoidal MMPs with micromanipulation and amplified their genomes using multiple displacement amplification. We sequenced the 16S rRNA gene and found 6.9% sequence divergence from that of ellipsoidal MMPs, Candidatus Magnetananas tsingtaoensis and > 8.3% divergence from those of spherical MMPs. Therefore, the novel MMPs belong to different species and genus compared with the currently known ellipsoidal and spherical MMPs respectively. The novel MMPs display a morphological cell differentiation, implying a potential division of labour. These findings provide new insights into the diversity of MMPs in general, and contribute to our understanding of the evolution of multicellularity among prokaryotes.}, } @article {pmid24717428, year = {2014}, author = {Ralston, KS and Solga, MD and Mackey-Lawrence, NM and Somlata, and Bhattacharya, A and Petri, WA}, title = {Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion.}, journal = {Nature}, volume = {508}, number = {7497}, pages = {526-530}, pmid = {24717428}, issn = {1476-4687}, support = {5R01 AI-26649/AI/NIAID NIH HHS/United States ; AI07046-32/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; T32 DK007769/DK/NIDDK NIH HHS/United States ; R37 AI026649/AI/NIAID NIH HHS/United States ; T32 AI055432/AI/NIAID NIH HHS/United States ; T32 AI007046/AI/NIAID NIH HHS/United States ; R01 AI026649/AI/NIAID NIH HHS/United States ; }, mesh = {Biological Evolution ; Caco-2 Cells ; Calcium/metabolism ; *Cell Death ; Cell Survival ; Entamoeba histolytica/cytology/*pathogenicity/*physiology ; Entamoebiasis/*parasitology/*pathology ; Erythrocytes/parasitology ; Humans ; Intestines/*parasitology/*pathology ; Jurkat Cells ; Neglected Diseases/parasitology/pathology ; }, abstract = {Entamoeba histolytica is the causative agent of amoebiasis, a potentially fatal diarrhoeal disease in the developing world. The parasite was named "histolytica" for its ability to destroy host tissues, which is probably driven by direct killing of human cells. The mechanism of human cell killing has been unclear, although the accepted model was that the parasites use secreted toxic effectors to kill cells before ingestion. Here we report the discovery that amoebae kill by ingesting distinct pieces of living human cells, resulting in intracellular calcium elevation and eventual cell death. After cell killing, amoebae detach and cease ingestion. Ingestion of human cell fragments is required for cell killing, and also contributes to invasion of intestinal tissue. The internalization of fragments of living human cells is reminiscent of trogocytosis (from Greek trogo, nibble) observed between immune cells, but amoebic trogocytosis differs because it results in death. The ingestion of live cell material and the rejection of corpses illuminate a stark contrast to the established model of dead cell clearance in multicellular organisms. These findings change the model for tissue destruction in amoebiasis and suggest an ancient origin of trogocytosis as a form of intercellular exchange.}, } @article {pmid24711645, year = {2014}, author = {Lovejoy, DA and Chang, BS and Lovejoy, NR and del Castillo, J}, title = {Molecular evolution of GPCRs: CRH/CRH receptors.}, journal = {Journal of molecular endocrinology}, volume = {52}, number = {3}, pages = {T43-60}, doi = {10.1530/JME-13-0238}, pmid = {24711645}, issn = {1479-6813}, mesh = {Adrenal Glands/physiology ; Animals ; Corticotropin-Releasing Hormone/*genetics ; Diuresis ; Energy Metabolism ; *Evolution, Molecular ; Hypothalamus/physiology ; Pituitary Gland/physiology ; Receptors, Corticotropin-Releasing Hormone/*genetics ; Signal Transduction ; Urocortins/genetics ; Urotensins/genetics ; }, abstract = {Corticotrophin-releasing hormone (CRH) is the pivotal neuroendocrine peptide hormone associated with the regulation of the stress response in vertebrates. However, CRH-like peptides are also found in a number of invertebrate species. The origin of this peptide can be traced to a common ancestor of lineages leading to chordates and to arthropods, postulated to occur some 500 million years ago. Evidence indicates the presence of a single CRH-like receptor and a soluble binding protein system that acted to transduce and regulate the actions of the early CRH peptide. In vertebrates, genome duplications led to the divergence of CRH receptors into CRH1 and CRH2 forms in tandem with the development of four paralogous ligand lineages that included CRH; urotensin I/urocortin (Ucn), Ucn2 and Ucn3. In addition, taxon-specific genome duplications led to further local divergences in CRH ligands and receptors. Functionally, the CRH ligand-receptor system evolved initially as a molecular system to integrate early diuresis and nutrient acquisition. As multicellular organisms evolved into more complex forms, this ligand-receptor system became integrated with the organismal stress response to coordinate homoeostatic challenges with internal energy usage. In vertebrates, CRH and the CRH1 receptor became associated with the hypothalamo-pituitary-adrenal/interrenal axis and the initial stress response, whereas the CRH2 receptor was selected to play a greater role in diuresis, nutrient acquisition and the latter aspects of the stress response.}, } @article {pmid24711388, year = {2014}, author = {Yang, C and Stiller, JW}, title = {Evolutionary diversity and taxon-specific modifications of the RNA polymerase II C-terminal domain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {16}, pages = {5920-5925}, pmid = {24711388}, issn = {1091-6490}, mesh = {Animals ; *Evolution, Molecular ; Fungi/metabolism ; *Genetic Variation ; *Phylogeny ; Plants/metabolism ; Protein Structure, Tertiary ; RNA Polymerase II/*chemistry/*genetics/metabolism ; Repetitive Sequences, Amino Acid ; Rhodophyta/metabolism ; }, abstract = {In model eukaryotes, the C-terminal domain (CTD) of the largest subunit of DNA-dependent RNA polymerase II (RNAP II) is composed of tandemly repeated heptads with the consensus sequence YSPTSPS. The core motif and tandem structure generally are conserved across model taxa, including animals, yeasts and higher plants. Broader investigations revealed that CTDs of many organisms deviate substantially from this canonical structure; however, limited sampling made it difficult to determine whether disordered sequences reflect the CTD's ancestral state or degeneration from ancestral repetitive structures. Therefore, we undertook, to our knowledge, the broadest investigation to date of the evolution of the RNAP II CTD across eukaryotic diversity. Our results indicate that a tandemly repeated CTD existed in the ancestors of each major taxon, and that degeneration and reinvention of this ordered structure are common features of CTD evolution. Lineage-specific CTD modifications appear to be associated with greater developmental complexity in multicellular organisms, a pattern taken to an extreme in fungi and red algae, in which the CTD has undergone dramatic to complete alteration during the transition from unicellular to developmentally complex forms. Overall, loss and reinvention of repeats have punctuated CTD evolution, occurring independently and sometimes repeatedly in various groups.}, } @article {pmid24704442, year = {2014}, author = {Newman, SA}, title = {Why are there eggs?.}, journal = {Biochemical and biophysical research communications}, volume = {450}, number = {3}, pages = {1225-1230}, doi = {10.1016/j.bbrc.2014.03.132}, pmid = {24704442}, issn = {1090-2104}, mesh = {Animals ; *Biological Evolution ; Body Patterning/physiology ; Chimera/growth & development ; Embryonic Development/physiology ; Female ; Fertilization/physiology ; Growth and Development/physiology ; Male ; *Models, Biological ; Ovum/*cytology/*physiology ; Species Specificity ; }, abstract = {A description and update of the "egg-as-novelty" hypothesis is presented. It is proposed that the major animal phylum-characteristic suites of morphological motifs first emerged more than a half-billion years ago in multicellular aggregates and clusters that did not exhibit an egg-soma divergence. These pre-metazoan bodies were organized by "dynamical patterning modules" (DPMs), physical processes and effects mobilized on the new multicellular scale by ancient conserved genes that came to mediate cell-cell interactions in these clusters. "Proto-eggs" were enlarged cells that through cleavage, or physical confinement by a secreted matrix, served to enforce genomic and genetic homogeneity in the cell clusters arising from them. Enlargement of the founder cell was the occasion for spontaneous intra-egg spatiotemporal organization based on single-cell physiological functions - calcium transients and oscillations, cytoplasmic flows - operating on the larger scale. Ooplasmic segregation by egg-patterning processes, while therefore not due to adaptive responses to external challenges, served as evolutionarily fertile "pre-adaptations" by making the implementation of the later-acting (at the multicellular "morphogenetic stage" of embryogenesis) DPMs more reliable, robust, and defining of sub-phylum morphotypes. This perspective is seen to account for a number of otherwise difficult to understand features of the evolution of development, such as the rapid diversification of biological forms with a conserved genetic toolkit at the dawn of animal evolution, the capability of even obligatory sexual reproducers to propagate vegetatively, and the "embryonic hourglass" of comparative developmental biology.}, } @article {pmid24696401, year = {2014}, author = {Carr, M and Suga, H}, title = {The holozoan Capsaspora owczarzaki possesses a diverse complement of active transposable element families.}, journal = {Genome biology and evolution}, volume = {6}, number = {4}, pages = {949-963}, pmid = {24696401}, issn = {1759-6653}, mesh = {DNA Transposable Elements/*physiology ; Eukaryota/*genetics ; *Evolution, Molecular ; Genome/*physiology ; }, abstract = {Capsaspora owczarzaki, a protistan symbiont of the pulmonate snail Biomphalaria glabrata, is the centre of much interest in evolutionary biology due to its close relationship to Metazoa. The whole genome sequence of this protist has revealed new insights into the ancestral genome composition of Metazoa, in particular with regard to gene families involved in the evolution of multicellularity. The draft genome revealed the presence of 23 families of transposable element, made up from DNA transposon as well as long terminal repeat (LTR) and non-LTR retrotransposon families. The phylogenetic analyses presented here show that all of the transposable elements identified in the C. owczarzaki genome have orthologous families in Metazoa, indicating that the ancestral metazoan also had a rich diversity of elements. Molecular evolutionary analyses also show that the majority of families has recently been active within the Capsaspora genome. One family now appears to be inactive and a further five families show no evidence of current transposition. Most individual element copies are evolutionarily young; however, a small proportion of inserts appear to have persisted for longer in the genome. The families present in the genome show contrasting population histories and appear to be in different stages of their life cycles. Transcriptome data have been analyzed from multiple stages in the C. owczarzaki life cycle. Expression levels vary greatly both between families and between different stages of the life cycle, suggesting an unexpectedly complex level of transposable element regulation in a single celled organism.}, } @article {pmid24691450, year = {2014}, author = {Brakel, J and Werner, FJ and Tams, V and Reusch, TB and Bockelmann, AC}, title = {Current European Labyrinthula zosterae are not virulent and modulate seagrass (Zostera marina) defense gene expression.}, journal = {PloS one}, volume = {9}, number = {4}, pages = {e92448}, pmid = {24691450}, issn = {1932-6203}, mesh = {Biomass ; Endophytes ; *Gene Expression Regulation, Plant ; Host-Pathogen Interactions/genetics/immunology ; Plant Leaves/growth & development ; Stramenopiles/*pathogenicity ; Zosteraceae/*genetics/growth & development/immunology/*parasitology ; }, abstract = {Pro- and eukaryotic microbes associated with multi-cellular organisms are receiving increasing attention as a driving factor in ecosystems. Endophytes in plants can change host performance by altering nutrient uptake, secondary metabolite production or defense mechanisms. Recent studies detected widespread prevalence of Labyrinthula zosterae in European Zostera marina meadows, a protist that allegedly caused a massive amphi-Atlantic seagrass die-off event in the 1930's, while showing only limited virulence today. As a limiting factor for pathogenicity, we investigated genotype × genotype interactions of host and pathogen from different regions (10-100 km-scale) through reciprocal infection. Although the endophyte rapidly infected Z. marina, we found little evidence that Z. marina was negatively impacted by L. zosterae. Instead Z. marina showed enhanced leaf growth and kept endophyte abundance low. Moreover, we found almost no interaction of protist × eelgrass-origin on different parameters of L. zosterae virulence/Z. marina performance, and also no increase in mortality after experimental infection. In a target gene approach, we identified a significant down-regulation in the expression of 6/11 genes from the defense cascade of Z. marina after real-time quantitative PCR, revealing strong immune modulation of the host's defense by a potential parasite for the first time in a marine plant. Nevertheless, one gene involved in phenol synthesis was strongly up-regulated, indicating that Z. marina plants were probably able to control the level of infection. There was no change in expression in a general stress indicator gene (HSP70). Mean L. zosterae abundances decreased below 10% after 16 days of experimental runtime. We conclude that under non-stress conditions L. zosterae infection in the study region is not associated with substantial virulence.}, } @article {pmid24689915, year = {2014}, author = {Hanschen, ER and Ferris, PJ and Michod, RE}, title = {Early evolution of the genetic basis for soma in the volvocaceae.}, journal = {Evolution; international journal of organic evolution}, volume = {68}, number = {7}, pages = {2014-2025}, doi = {10.1111/evo.12416}, pmid = {24689915}, issn = {1558-5646}, mesh = {Cell Differentiation ; *Evolution, Molecular ; *Gene Duplication ; *Genes, Plant ; Phylogeny ; Volvox/cytology/*genetics ; }, abstract = {To understand the hierarchy of life in evolutionary terms, we must explain why groups of one kind of individual, say cells, evolve into a new higher level individual, a multicellular organism. A fundamental step in this process is the division of labor into nonreproductive altruistic soma. The regA gene is critical for somatic differentiation in Volvox carteri, a multicellular species of volvocine algae. We report the sequence of regA-like genes and several syntenic markers from divergent species of Volvox. We show that regA evolved early in the volvocines and predict that lineages with and without soma descended from a regA-containing ancestor. We hypothesize an alternate evolutionary history of regA than the prevailing "proto-regA" hypothesis. The variation in presence of soma may be explained by multiple lineages independently evolving soma utilizing regA or alternate genetic pathways. Our prediction that the genetic basis for soma exists in species without somatic cells raises a number of questions, most fundamentally, under what conditions would species with the genetic potential for soma, and hence greater individuality, not evolve these traits. We conclude that the evolution of individuality in the volvocine algae is more complicated and labile than previously appreciated on theoretical grounds.}, } @article {pmid24679530, year = {2014}, author = {Sánchez Alvarado, A and Yamanaka, S}, title = {Rethinking differentiation: stem cells, regeneration, and plasticity.}, journal = {Cell}, volume = {157}, number = {1}, pages = {110-119}, pmid = {24679530}, issn = {1097-4172}, support = {R37 GM057260/GM/NIGMS NIH HHS/United States ; R37GM057260/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; *Cell Differentiation ; Humans ; Plant Cells/physiology ; Plants/embryology ; Pluripotent Stem Cells/cytology ; Regeneration ; Stem Cells/*cytology/physiology ; }, abstract = {Cell differentiation is an essential process for the development, growth, reproduction, and longevity of all multicellular organisms, and its regulation has been the focus of intense investigation for the past four decades. The study of natural and induced stem cells has ushered an age of re-examination of what it means to be a stem or a differentiated cell. Past and recent discoveries in plants and animals, as well as novel experimental manipulations, are beginning to erode many of these established concepts and are forcing a re-evaluation of the experimental systems and paradigms presently being used to explore these and other biological process.}, } @article {pmid24678663, year = {2014}, author = {Nakanishi, N and Sogabe, S and Degnan, BM}, title = {Evolutionary origin of gastrulation: insights from sponge development.}, journal = {BMC biology}, volume = {12}, number = {}, pages = {26}, pmid = {24678663}, issn = {1741-7007}, mesh = {Animals ; Apoptosis/genetics ; *Biological Evolution ; Cell Lineage ; Epithelium/embryology ; GATA Transcription Factors/genetics/metabolism ; *Gastrulation ; Gene Expression Regulation, Developmental ; Germ Layers/embryology ; Larva/genetics/ultrastructure ; Metamorphosis, Biological/genetics ; Phagocytosis ; Phylogeny ; Porifera/cytology/*embryology/genetics ; RNA, Messenger/genetics/metabolism ; }, abstract = {BACKGROUND: The evolutionary origin of gastrulation--defined as a morphogenetic event that leads to the establishment of germ layers--remains a vexing question. Central to this debate is the evolutionary relationship between the cell layers of sponges (poriferans) and eumetazoan germ layers. Despite considerable attention, it remains unclear whether sponge cell layers undergo progressive fate determination akin to eumetazoan primary germ layer formation during gastrulation.

RESULTS: Here we show by cell-labelling experiments in the demosponge Amphimedon queenslandica that the cell layers established during embryogenesis have no relationship to the cell layers of the juvenile. In addition, juvenile epithelial cells can transdifferentiate into a range of cell types and move between cell layers. Despite the apparent lack of cell layer and fate determination and stability in this sponge, the transcription factor GATA, a highly conserved eumetazoan endomesodermal marker, is expressed consistently in the inner layer of A. queenslandica larvae and juveniles.

CONCLUSIONS: Our results are compatible with sponge cell layers not undergoing progressive fate determination and thus not being homologous to eumetazoan germ layers. Nonetheless, the expression of GATA in the sponge inner cell layer suggests a shared ancestry with the eumetazoan endomesoderm, and that the ancestral role of GATA in specifying internalised cells may antedate the origin of germ layers. Together, these results support germ layers and gastrulation evolving early in eumetazoan evolution from pre-existing developmental programs used for the simple patterning of cells in the first multicellular animals.}, } @article {pmid24659336, year = {2014}, author = {Irian, S}, title = {Large-scale tag/PCR-based gene expression profiling.}, journal = {World journal of microbiology & biotechnology}, volume = {30}, number = {8}, pages = {2125-2139}, pmid = {24659336}, issn = {1573-0972}, mesh = {Gene Expression Profiling ; Genome ; Nucleic Acid Hybridization ; Polymerase Chain Reaction/economics/*methods/trends ; Polymorphism, Restriction Fragment Length ; }, abstract = {An intriguing enigma in molecular biology is how genes within a single genome are differentially expressed in different cell types of a multicellular organism, or in response to different developmental or environmental queues in a single cell type. Quantification of transcript levels on a genome-wide scale, often termed transcript profiling, provides a powerful approach to identifying protein-coding and non-coding RNAs functionally relevant to a given biological process. Indeed, transcriptome analysis has been a key area of biological inquiry for decades and successfully produced discoveries in a multitude of processes and disease states, and in an increasingly large number of organisms. The evolution of technologies with increasing levels of informational content, ranging from hybridization-based technologies such as Northern blot analysis and microarrays to tag/polymerase chain reaction (PCR)- and sequence-based technologies including differential display and SAGE, along with the next-generation sequencing, has provided hope for revealing the molecular details of biological systems as they respond to change. This review is an overview of selected high throughput tag/PCR-based methods for genome-wide expression profiling amenable to high-throughput automated operation in any standard laboratory.}, } @article {pmid24656331, year = {2014}, author = {Lee, JY}, title = {New and old roles of plasmodesmata in immunity and parallels to tunneling nanotubes.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {221-222}, number = {}, pages = {13-20}, pmid = {24656331}, issn = {1873-2259}, support = {P30 GM103519/GM/NIGMS NIH HHS/United States ; 8P30 GM103519-03/GM/NIGMS NIH HHS/United States ; 5P30 RR031160-03/RR/NCRR NIH HHS/United States ; }, mesh = {Biological Evolution ; Cell Communication ; Nanotubes/*chemistry ; Plants/*immunology ; Plasmodesmata/*immunology ; Signal Transduction ; }, abstract = {Effective cell-to-cell communication is critical for the survival of both unicellular and multicellular organisms. In multicellular plants, direct cell coupling across the cell wall boundaries is mediated by long membrane-lined cytoplasmic bridges, the plasmodesmata. Exciting recent discoveries suggest that the occurrence of such membrane-lined intercellular channels is not unique to plant lineages but more prevalent across biological kingdoms than previously assumed. Striking functional analogies exist among those channels, in that not only do they all facilitate the exchange of various forms of macromolecules, but also they are exploited by some opportunistic pathogens to spread infection from one host cell to another. However, host cells may have also evolved strategies to offset such exploitation of the critical cellular infrastructure by the pathogen. Indeed, recent studies support an emerging paradigm that cellular connectivity via plasmodesmata plays an important role in innate immune responses. Preliminary hypotheses are proposed as to how various regulatory mechanisms integrating plasmodesmata into immune signaling pathways may have evolved.}, } @article {pmid24652835, year = {2014}, author = {Messina, G and Damia, E and Fanti, L and Atterrato, MT and Celauro, E and Mariotti, FR and Accardo, MC and Walther, M and Vernì, F and Picchioni, D and Moschetti, R and Caizzi, R and Piacentini, L and Cenci, G and Giordano, E and Dimitri, P}, title = {Yeti, an essential Drosophila melanogaster gene, encodes a protein required for chromatin organization.}, journal = {Journal of cell science}, volume = {127}, number = {Pt 11}, pages = {2577-2588}, doi = {10.1242/jcs.150243}, pmid = {24652835}, issn = {1477-9137}, mesh = {Animals ; Animals, Genetically Modified ; Carrier Proteins/genetics/metabolism ; Cells, Cultured ; Chromatin Assembly and Disassembly/genetics ; Conserved Sequence/genetics ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/*physiology ; Evolution, Molecular ; Histones/metabolism ; Mutation/genetics ; Nuclear Proteins ; Phosphoproteins/genetics/*metabolism ; Polytene Chromosomes/*metabolism ; Protein Binding ; Signal Transduction ; Transcription Factors/*metabolism ; }, abstract = {The evolutionarily conserved family of Bucentaur (BCNT) proteins exhibits a widespread distribution in animal and plants, yet its biological role remains largely unknown. Using Drosophila melanogaster as a model organism, we investigated the in vivo role of the Drosophila BCNT member called YETI. We report that loss of YETI causes lethality before pupation and defects in higher-order chromatin organization, as evidenced by severe impairment in the association of histone H2A.V, nucleosomal histones and epigenetic marks with polytene chromosomes. We also find that YETI binds to polytene chromosomes through its conserved BCNT domain and interacts with the histone variant H2A.V, HP1a and Domino-A (DOM-A), the ATPase subunit of the DOM/Tip60 chromatin remodeling complex. Furthermore, we identify YETI as a downstream target of the Drosophila DOM-A. On the basis of these results, we propose that YETI interacts with H2A.V-exchanging machinery, as a chaperone or as a new subunit of the DOM/Tip60 remodeling complex, and acts to regulate the accumulation of H2A.V at chromatin sites. Overall, our findings suggest an unanticipated role of YETI protein in chromatin organization and provide, for the first time, mechanistic clues on how BCNT proteins control development in multicellular organisms.}, } @article {pmid24642410, year = {2014}, author = {Hudry, B and Thomas-Chollier, M and Volovik, Y and Duffraisse, M and Dard, A and Frank, D and Technau, U and Merabet, S}, title = {Molecular insights into the origin of the Hox-TALE patterning system.}, journal = {eLife}, volume = {3}, number = {}, pages = {e01939}, pmid = {24642410}, issn = {2050-084X}, support = {P 24858/FWF_/Austrian Science Fund FWF/Austria ; P 27353/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; Animals, Genetically Modified ; Binding Sites ; *Body Patterning ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/embryology/genetics/*metabolism ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/genetics/*metabolism ; Phylogeny ; Promoter Regions, Genetic ; Protein Binding ; Sea Anemones/embryology/genetics/metabolism ; Species Specificity ; Transcription Factors/genetics/*metabolism ; Xenopus/embryology/genetics/*metabolism ; Xenopus Proteins/genetics/*metabolism ; }, abstract = {Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior-posterior axis. Hox proteins exert their function by interaction with TALE transcription factors. Hox and TALE members are also present in some but not all non-bilaterian phyla, raising the question of how Hox-TALE interactions evolved to provide positional information. By using proteins from unicellular and multicellular lineages, we showed that these networks emerged from an ancestral generic motif present in Hox and other related protein families. Interestingly, Hox-TALE networks experienced additional and extensive molecular innovations that were likely crucial for differentiating Hox functions along body plans. Together our results highlight how homeobox gene families evolved during eukaryote evolution to eventually constitute a major patterning system in Eumetazoans. DOI: http://dx.doi.org/10.7554/eLife.01939.001.}, } @article {pmid24633620, year = {2014}, author = {Niklas, KJ and Kutschera, U}, title = {Amphimixis and the individual in evolving populations: does Weismann's Doctrine apply to all, most or a few organisms?.}, journal = {Die Naturwissenschaften}, volume = {101}, number = {5}, pages = {357-372}, pmid = {24633620}, issn = {1432-1904}, mesh = {Animals ; Bacterial Physiological Phenomena ; *Biological Evolution ; Life Cycle Stages ; Plant Physiological Phenomena ; Reproduction/*physiology ; }, abstract = {The German biologist August Weismann (1834-1914) proposed that amphimixis (sexual reproduction) creates variability for natural selection to act upon, and hence he became one of the founders of the Neo-Darwinian theory of biological evolution. He is perhaps best known for what is called "Weismann's Doctrine" or "Weismann's Barrier" (i.e. the irreversible separation of somatic and germ cell functionalities early during ontogeny in multicellular organisms). This concept provided an unassailable argument against "soft inheritance" sensu Lamarck and informed subsequent theorists that the only "individual" in the context of evolution is the mature, reproductive organism. Herein, we review representative model organisms whose embryology conforms to Weismann's Doctrine (e.g. flies and mammals) and those that do not (e.g. freshwater hydroids and plants) based on this survey and the Five Kingdoms of Life scheme; we point out that most species (notably bacteria, fungi, protists and plants) are "non-Weismannian" in ways that make a canonical definition of the "individual" problematic if not impossible. We also review critical life history functional traits that allow us to create a matrix of all theoretically conceivable life cycles (for eukaryotic algae, embryophytes, fungi and animals), which permits us to establish where this scheme Weismann's Doctrine holds true and where it does not. In addition, we argue that bacteria, the dominant organisms of the biosphere, exist in super-cellular biofilms but rarely as single (planktonic) microbes. Our analysis attempts to show that competition among genomic variants in cell lineages played a critical part in the evolution of multicellularity and life cycle diversity. This feature was largely ignored during the formulation of the synthetic theory of biological evolution and its subsequent elaborations.}, } @article {pmid24614804, year = {2014}, author = {McCracken, A and Locke, J}, title = {Mutations in CG8878, a novel putative protein kinase, enhance P element dependent silencing (PDS) and position effect variegation (PEV) in Drosophila melanogaster.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e71695}, pmid = {24614804}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Chromobox Protein Homolog 5 ; Chromosomal Position Effects/*genetics ; DNA Transposable Elements/*genetics ; Drosophila Proteins/*genetics ; Drosophila melanogaster/*enzymology/*genetics ; Enhancer Elements, Genetic/genetics ; Evolution, Molecular ; Female ; *Gene Silencing ; Humans ; Magnetic Resonance Spectroscopy ; Male ; Models, Molecular ; Molecular Sequence Data ; Mutation/*genetics ; Phenotype ; Phylogeny ; Protein Kinases/*genetics ; Protein Serine-Threonine Kinases/*genetics ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; }, abstract = {Genes in multicellular organisms are expressed as part of a developmental program that is largely dependent on self-perpetuating higher-order chromatin states. The mechanism of establishing and maintaining these epigenetic events is well studied in Drosophila. The first known example of an epigenetic effect was that of (PEV) in Drosophila, which has been shown to be due to gene silencing via heterochromatin formation. We are investigating a process similar to Position Effect Variegation (PEV) using a mini-w transgene, called Pci, inserted in the upstream regulatory region of ci. The mini-white+ transgene in Pci is expressed throughout the adult eye; however, when other P or KP elements are present, a variegated eye phenotype results indicating random w+ silencing during development. This P element dependent silencing (PDS) can be modified by the haplo-suppressors/triplo-enhancers, Su(var)205 and Su(var)3-7, indicating that these heterochromatic modifiers also act dose dependently in PDS. Here we use a spontaneous derivative mutation of Pci called PciE1 (E1) that variegates like PDS in the absence of P elements, presumably due to an adjacent gypsy element insertion, to screen for second-site modifier mutations that enhance variable silencing of white+ in E1. We isolated 7 mutations in CG8878, an essential gene, that enhance the E1 variegated phenotype. CG8878, a previously uncharacterized gene, potentially encodes a serine/threonine kinase whose closest Drosophila paralogue, ballchen (nhk-1), phosphorylates histones. These mutant alleles enhance both PDS at E1 and Position Effect Variegation (PEV) at w(m4), indicating a previously unknown common silencing mechanism between the two.}, } @article {pmid24604070, year = {2014}, author = {Gombar, S and MacCarthy, T and Bergman, A}, title = {Epigenetics decouples mutational from environmental robustness. Did it also facilitate multicellularity?.}, journal = {PLoS computational biology}, volume = {10}, number = {3}, pages = {e1003450}, pmid = {24604070}, issn = {1553-7358}, support = {R01 AG028872/AG/NIA NIH HHS/United States ; R01-AG028872/AG/NIA NIH HHS/United States ; P01 AG027734/AG/NIA NIH HHS/United States ; T32 GM007288/GM/NIGMS NIH HHS/United States ; P01-AG027734/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; DNA Mutational Analysis ; Drosophila melanogaster ; Environment ; *Epigenesis, Genetic ; Evolution, Molecular ; *Gene Regulatory Networks ; Gene-Environment Interaction ; Genetic Association Studies ; Histones/chemistry ; *Mutation ; Polycomb-Group Proteins/metabolism ; }, abstract = {The evolution of ever increasing complex life forms has required innovations at the molecular level in order to overcome existing barriers. For example, evolving processes for cell differentiation, such as epigenetic mechanisms, facilitated the transition to multicellularity. At the same time, studies using gene regulatory network models, and corroborated in single-celled model organisms, have shown that mutational robustness and environmental robustness are correlated. Such correlation may constitute a barrier to the evolution of multicellularity since cell differentiation requires sensitivity to cues in the internal environment during development. To investigate how this barrier might be overcome, we used a gene regulatory network model which includes epigenetic control based on the mechanism of histone modification via Polycomb Group Proteins, which evolved in tandem with the transition to multicellularity. Incorporating the Polycomb mechanism allowed decoupling of mutational and environmental robustness, thus allowing the system to be simultaneously robust to mutations while increasing sensitivity to the environment. In turn, this decoupling facilitated cell differentiation which we tested by evaluating the capacity of the system for producing novel output states in response to altered initial conditions. In the absence of the Polycomb mechanism, the system was frequently incapable of adding new states, whereas with the Polycomb mechanism successful addition of new states was nearly certain. The Polycomb mechanism, which dynamically reshapes the network structure during development as a function of expression dynamics, decouples mutational and environmental robustness, thus providing a necessary step in the evolution of multicellularity.}, } @article {pmid24603697, year = {2014}, author = {Moine, A and Agrebi, R and Espinosa, L and Kirby, JR and Zusman, DR and Mignot, T and Mauriello, EM}, title = {Functional organization of a multimodular bacterial chemosensory apparatus.}, journal = {PLoS genetics}, volume = {10}, number = {3}, pages = {e1004164}, pmid = {24603697}, issn = {1553-7404}, support = {R01 GM020509/GM/NIGMS NIH HHS/United States ; }, mesh = {Biofilms/growth & development ; Cell Movement/genetics ; Chemotaxis/*genetics ; *Gene Expression Regulation, Bacterial ; Movement ; Myxococcus xanthus/chemistry/*genetics/growth & development ; Phylogeny ; Signal Transduction/*genetics ; }, abstract = {Chemosensory systems (CSS) are complex regulatory pathways capable of perceiving external signals and translating them into different cellular behaviors such as motility and development. In the δ-proteobacterium Myxococcus xanthus, chemosensing allows groups of cells to orient themselves and aggregate into specialized multicellular biofilms termed fruiting bodies. M. xanthus contains eight predicted CSS and 21 chemoreceptors. In this work, we systematically deleted genes encoding components of each CSS and chemoreceptors and determined their effects on M. xanthus social behaviors. Then, to understand how the 21 chemoreceptors are distributed among the eight CSS, we examined their phylogenetic distribution, genomic organization and subcellular localization. We found that, in vivo, receptors belonging to the same phylogenetic group colocalize and interact with CSS components of the respective phylogenetic group. Finally, we identified a large chemosensory module formed by three interconnected CSS and multiple chemoreceptors and showed that complex behaviors such as cell group motility and biofilm formation require regulatory apparatus composed of multiple interconnected Che-like systems.}, } @article {pmid24583766, year = {2014}, author = {Hardie, DG and Ashford, ML}, title = {AMPK: regulating energy balance at the cellular and whole body levels.}, journal = {Physiology (Bethesda, Md.)}, volume = {29}, number = {2}, pages = {99-107}, pmid = {24583766}, issn = {1548-9221}, support = {/WT_/Wellcome Trust/United Kingdom ; 097726/WT_/Wellcome Trust/United Kingdom ; MR/K003291/1/MRC_/Medical Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {AMP-Activated Protein Kinases/*metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Calcium/metabolism ; Energy Metabolism/*physiology ; Homeostasis/*physiology ; Hormones/metabolism ; Humans ; }, abstract = {AMP-activated protein kinase appears to have evolved in single-celled eukaryotes as an adenine nucleotide sensor that maintains energy homeostasis at the cellular level. However, during evolution of more complex multicellular organisms, the system has adapted to interact with hormones so that it also plays a key role in balancing energy intake and expenditure at the whole body level.}, } @article {pmid24567306, year = {2014}, author = {de Mendoza, A and Sebé-Pedrós, A and Ruiz-Trillo, I}, title = {The evolution of the GPCR signaling system in eukaryotes: modularity, conservation, and the transition to metazoan multicellularity.}, journal = {Genome biology and evolution}, volume = {6}, number = {3}, pages = {606-619}, pmid = {24567306}, issn = {1759-6653}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Animals ; Arrestin/genetics ; Eukaryota/*classification/*genetics ; Evolution, Molecular ; Eye Proteins/genetics ; G-Protein-Coupled Receptor Kinases/genetics ; GTP-Binding Protein Regulators/genetics ; Genome ; Multigene Family ; Phosphoproteins/genetics ; Phylogeny ; Principal Component Analysis ; Receptors, G-Protein-Coupled/*genetics ; Signal Transduction/*genetics ; }, abstract = {The G-protein-coupled receptor (GPCR) signaling system is one of the main signaling pathways in eukaryotes. Here, we analyze the evolutionary history of all its components, from receptors to regulators, to gain a broad picture of its system-level evolution. Using eukaryotic genomes covering most lineages sampled to date, we find that the various components of the GPCR signaling pathway evolved independently, highlighting the modular nature of this system. Our data show that some GPCR families, G proteins, and regulators of G proteins diversified through lineage-specific diversifications and recurrent domain shuffling. Moreover, most of the gene families involved in the GPCR signaling system were already present in the last common ancestor of eukaryotes. Furthermore, we show that the unicellular ancestor of Metazoa already had most of the cytoplasmic components of the GPCR signaling system, including, remarkably, all the G protein alpha subunits, which are typical of metazoans. Thus, we show how the transition to multicellularity involved conservation of the signaling transduction machinery, as well as a burst of receptor diversification to cope with the new multicellular necessities.}, } @article {pmid24563351, year = {2014}, author = {Lyakhovetsky, R and Gruenbaum, Y}, title = {Studying lamins in invertebrate models.}, journal = {Advances in experimental medicine and biology}, volume = {773}, number = {}, pages = {245-262}, doi = {10.1007/978-1-4899-8032-8_11}, pmid = {24563351}, issn = {0065-2598}, mesh = {Animals ; Lamins/chemistry/genetics/*physiology ; *Models, Biological ; Molecular Structure ; Phylogeny ; }, abstract = {Lamins are nuclear intermediate filament proteins that are conserved in all multicellular animals. Proteins that resemble lamins are also found in unicellular organisms and in plants. Lamins form a proteinaceous meshwork that outlines the nucleoplasmic side of the inner nuclear membrane, while a small fraction of lamin molecules is also present in the nucleoplasm. They provide structural support for the nucleus and help regulate many other nuclear activities. Much of our knowledge on the function of nuclear lamins and their associated proteins comes from studies in invertebrate organisms and specifically in the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. The simpler lamin system and the powerful genetic tools offered by these model organisms greatly promote such studies. Here we provide an overview of recent advances in the biology of invertebrate nuclear lamins, with special emphasis on their assembly, cellular functions and as models for studying the molecular basis underlying the pathology of human heritable diseases caused by mutations in lamins A/C.}, } @article {pmid24561726, year = {2014}, author = {Williams, F and Tew, HA and Paul, CE and Adams, JC}, title = {The predicted secretomes of Monosiga brevicollis and Capsaspora owczarzaki, close unicellular relatives of metazoans, reveal new insights into the evolution of the metazoan extracellular matrix.}, journal = {Matrix biology : journal of the International Society for Matrix Biology}, volume = {37}, number = {}, pages = {60-68}, doi = {10.1016/j.matbio.2014.02.002}, pmid = {24561726}, issn = {1569-1802}, mesh = {Amino Acid Sequence ; *Biological Evolution ; Choanoflagellata/*metabolism ; Extracellular Matrix/*metabolism ; Extracellular Matrix Proteins/genetics/*metabolism ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Sequence Alignment ; Signal Transduction/*physiology ; Species Specificity ; }, abstract = {The extracellular matrix (ECM) is a major mediator of multi-cellularity in the metazoa. Multiple ECM proteins are conserved from sponges to human, raising questions about the evolutionary origin of ECM. Choanoflagellates are the closest unicellular relatives of the metazoa and proteins with domains characteristic of metazoan ECM proteins have been identified from the genome-predicted proteome of the choanoflagellate Monosiga brevicollis. However, a systematic analysis of M. brevicollis secretory signal peptide-containing proteins with ECM domains has been lacking. We analysed all predicted secretory signal-peptide-containing proteins of M. brevicollis for ECM domains. Nine domains that are widespread in metazoan ECM proteins are represented, with EGF, fibronectin III, laminin G, and von Willebrand Factor_A domains being the most numerous. Three proteins contain more than one category of ECM domain, however, no proteins correspond to the domain architecture of metazoan ECM proteins. The fibronectin III domains are all present within glycoside hydrolases and none contain an integrin-binding motif. Glycosaminoglycan-binding motifs identified in animal thrombospondin type 1 domains are conserved in some M. brevicollis representatives of this domain, whereas there is little evidence of conservation of glycosaminoglycan-binding motifs in the laminin G domains. The identified proteins were compared with the predicted secretory ECM domain-containing proteins of the integrin-expressing filasterean, Capsaspora owczarzaki. C. owczarzaki encodes a smaller number of secretory, ECM domain-containing proteins and only EGF, fibronectin type III and laminin G domains are represented. The M. brevicollis and C. owczarzaki proteins have distinct domain architectures and all proteins differ in their domain architecture to metazoan ECM proteins. These identifications provide a basis for future experiments to validate the extracellular location of these proteins and uncover their functions in choanoflagellates and C. owczarzaki. The data strengthen the model that ECM proteins are metazoan-specific and evolved as innovations in the last common metazoan ancestor.}, } @article {pmid24555417, year = {2013}, author = {Gong, H}, title = {Analysis of intercellular signal transduction in the tumor microenvironment.}, journal = {BMC systems biology}, volume = {7 Suppl 3}, number = {Suppl 3}, pages = {S5}, pmid = {24555417}, issn = {1752-0509}, mesh = {Extracellular Space/*metabolism ; G1 Phase ; Models, Biological ; Pancreatic Neoplasms/*metabolism/*pathology ; Pancreatic Stellate Cells/pathology ; S Phase ; *Signal Transduction ; Systems Biology/*methods ; *Tumor Microenvironment ; Tumor Suppressor Proteins/metabolism ; }, abstract = {BACKGROUND: Recent cancer studies revealed, the interaction between pancreatic cancer cells and pancreatic stellate cells is of importance in the cancer progression. The activation of stellate cells is mediated by some growth factors and cytokines secreted by the cancer cells. In turn, the activated stellate cells will synthesize and secrete multiple growth factors to continuously stimulate the growth of surrounding cancer cells through paracrine pathways. The mechanism behind the evolution of stellate cells from quiescent state to a cancer-associated phenotype is still not well understood.

RESULTS: To systematically investigate the interaction between cancer cells and stellate cells, we constructed a multicellular discrete value model, which is composed of several intracellular and intercellular signaling pathways that are frequently mutated in the pancreatic cancer, to study the cell cycle progression and angiogenesis. We, then, introduced and applied a formal verification technique, Symbolic Model Checking, to automatically analyze the cells' proliferation, angiogenesis and apoptosis in the proposed signal transduction model of tumor microenvironment.

CONCLUSIONS: Our studies predicted some important temporal logic properties and dynamic behaviors in the pancreatic cancer cells and stellate cells. The verification technique identified several signaling components, including the RAS, RAGE, AKT, IKK, DVL, RB and PTEN, whose mutation or loss of function can promote cell growth and inhibit apoptosis, some of which have been confirmed by existing experiments. Our formal studies demonstrated that, the bidirectional interaction between cancer cells and stellate cells could significantly increase cell proliferation, inhibit apoptosis, induce tumor angiogenesis, and promote cancer metastasis.}, } @article {pmid24554920, year = {2013}, author = {Sciumè, G and Shelton, S and Gray, W and Miller, C and Hussain, F and Ferrari, M and Decuzzi, P and Schrefler, B}, title = {A multiphase model for three-dimensional tumor growth.}, journal = {New journal of physics}, volume = {15}, number = {}, pages = {015005}, pmid = {24554920}, issn = {1367-2630}, support = {U54 CA143837/CA/NCI NIH HHS/United States ; U54 CA151668/CA/NCI NIH HHS/United States ; }, abstract = {Several mathematical formulations have analyzed the time-dependent behaviour of a tumor mass. However, most of these propose simplifications that compromise the physical soundness of the model. Here, multiphase porous media mechanics is extended to model tumor evolution, using governing equations obtained via the Thermodynamically Constrained Averaging Theory (TCAT). A tumor mass is treated as a multiphase medium composed of an extracellular matrix (ECM); tumor cells (TC), which may become necrotic depending on the nutrient concentration and tumor phase pressure; healthy cells (HC); and an interstitial fluid (IF) for the transport of nutrients. The equations are solved by a Finite Element method to predict the growth rate of the tumor mass as a function of the initial tumor-to-healthy cell density ratio, nutrient concentration, mechanical strain, cell adhesion and geometry. Results are shown for three cases of practical biological interest such as multicellular tumor spheroids (MTS) and tumor cords. First, the model is validated by experimental data for time-dependent growth of an MTS in a culture medium. The tumor growth pattern follows a biphasic behaviour: initially, the rapidly growing tumor cells tend to saturate the volume available without any significant increase in overall tumor size; then, a classical Gompertzian pattern is observed for the MTS radius variation with time. A core with necrotic cells appears for tumor sizes larger than 150 μm, surrounded by a shell of viable tumor cells whose thickness stays almost constant with time. A formula to estimate the size of the necrotic core is proposed. In the second case, the MTS is confined within a healthy tissue. The growth rate is reduced, as compared to the first case - mostly due to the relative adhesion of the tumor and healthy cells to the ECM, and the less favourable transport of nutrients. In particular, for tumor cells adhering less avidly to the ECM, the healthy tissue is progressively displaced as the malignant mass grows, whereas tumor cell infiltration is predicted for the opposite condition. Interestingly, the infiltration potential of the tumor mass is mostly driven by the relative cell adhesion to the ECM. In the third case, a tumor cord model is analyzed where the malignant cells grow around microvessels in a 3D geometry. It is shown that tumor cells tend to migrate among adjacent vessels seeking new oxygen and nutrient. This model can predict and optimize the efficacy of anticancer therapeutic strategies. It can be further developed to answer questions on tumor biophysics, related to the effects of ECM stiffness and cell adhesion on tumor cell proliferation.}, } @article {pmid24552098, year = {2013}, author = {Frederickson, ME}, title = {Rethinking mutualism stability: cheaters and the evolution of sanctions.}, journal = {The Quarterly review of biology}, volume = {88}, number = {4}, pages = {269-295}, doi = {10.1086/673757}, pmid = {24552098}, issn = {0033-5770}, mesh = {Animals ; *Biological Evolution ; Insecta/physiology ; Magnoliopsida/physiology ; Rhizobium/physiology ; *Symbiosis ; }, abstract = {How cooperation originates and persists in diverse species, from bacteria to multicellular organisms to human societies, is a major question in evolutionary biology. A large literature asks: what prevents selection for cheating within cooperative lineages? In mutualisms, or cooperative interactions between species, feedback between partners often aligns their fitness interests, such that cooperative symbionts receive more benefits from their hosts than uncooperative symbionts. But how do these feedbacks evolve? Cheaters might invade symbiont populations and select for hosts that preferentially reward or associate with cooperators (often termed sanctions or partner choice); hosts might adapt to variation in symbiont quality that does not amount to cheating (e.g., environmental variation); or conditional host responses might exist before cheaters do, making mutualisms stable from the outset. I review evidence from yucca-yucca moth, fig-fig wasp, and legume-rhizobium mutualisms, which are commonly cited as mutualisms stabilized by sanctions. Based on the empirical evidence, it is doubtful that cheaters select for host sanctions in these systems; cheaters are too uncommon. Recognizing that sanctions likely evolved for functions other than retaliation against cheaters offers many insights about mutualism coevolution, and about why mutualism evolves in only some lineages of potential hosts.}, } @article {pmid24520931, year = {2014}, author = {Schultheiss, KP and Craddock, BP and Suga, H and Miller, WT}, title = {Regulation of Src and Csk nonreceptor tyrosine kinases in the filasterean Ministeria vibrans.}, journal = {Biochemistry}, volume = {53}, number = {8}, pages = {1320-1329}, pmid = {24520931}, issn = {1520-4995}, support = {R01 CA058530/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; CSK Tyrosine-Protein Kinase ; Cloning, Molecular ; Eukaryota/*enzymology ; HEK293 Cells ; Humans ; Models, Molecular ; Protein Structure, Tertiary ; Sequence Homology ; src-Family Kinases/chemistry/genetics/*metabolism ; }, abstract = {The development of the phosphotyrosine-based signaling system predated the evolution of multicellular animals. Single-celled choanoflagellates, the closest living relatives to metazoans, possess numerous tyrosine kinases, including Src family nonreceptor tyrosine kinases. Choanoflagellates also have Csk (C-terminal Src kinase), the enzyme that regulates Src in metazoans; however, choanoflagellate Csk kinases fail to repress the cognate Src. Here, we have cloned and characterized Src and Csk kinases from Ministeria vibrans, a filasterean (the sister group to metazoans and choanoflagellates). The two Src kinases (MvSrc1 and MvSrc2) are enzymatically active Src kinases, although they have low activity toward mammalian cellular proteins. Unexpectedly, MvSrc2 has significant Ser/Thr kinase activity. The Csk homologue (MvCsk) is enzymatically inactive and fails to repress MvSrc activity. We suggest that the low activity of MvCsk is due to sequences in the SH2-kinase interface, and we show that a point mutation in this region partially restores MvCsk activity. The inactivity of filasterean Csk kinases is consistent with a model in which the stringent regulation of Src family kinases arose more recently in evolution, after the split between choanoflagellates and multicellular animals.}, } @article {pmid24510140, year = {2013}, author = {Stucken, K and Koch, R and Dagan, T}, title = {Cyanobacterial defense mechanisms against foreign DNA transfer and their impact on genetic engineering.}, journal = {Biological research}, volume = {46}, number = {4}, pages = {373-382}, doi = {10.4067/S0716-97602013000400009}, pmid = {24510140}, issn = {0717-6287}, mesh = {Amino Acid Sequence ; Bacterial Proteins/*genetics ; Base Sequence ; Cyanobacteria/*genetics ; DNA, Bacterial/*genetics ; Gene Transfer Techniques ; Phylogeny ; }, abstract = {Cyanobacteria display a large diversity of cellular forms ranging from unicellular to complex multicellular filaments or aggregates. Species in the group present a wide range of metabolic characteristics including the fixation of atmospheric nitrogen, resistance to extreme environments, production of hydrogen, secondary metabolites and exopolysaccharides. These characteristics led to the growing interest in cyanobacteria across the fields of ecology, evolution, cell biology and biotechnology. The number of available cyanobacterial genome sequences has increased considerably in recent years, with more than 140 fully sequenced genomes to date. Genetic engineering of cyanobacteria is widely applied to the model unicellular strains Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942. However the establishment of transformation protocols in many other cyanobacterial strains is challenging. One obstacle to the development of these novel model organisms is that many species have doubling times of 48 h or more, much longer than the bacterial models E. coli or B. subtilis. Furthermore, cyanobacterial defense mechanisms against foreign DNA pose a physical and biochemical barrier to DNA insertion in most strains. Here we review the various barriers to DNA uptake in the context of lateral gene transfer among microbes and the various mechanisms for DNA acquisition within the prokaryotic domain. Understanding the cyanobacterial defense mechanisms is expected to assist in the development and establishment of novel transformation protocols that are specifically suitable for this group.}, } @article {pmid24507487, year = {2014}, author = {Cock, JM and Godfroy, O and Macaisne, N and Peters, AF and Coelho, SM}, title = {Evolution and regulation of complex life cycles: a brown algal perspective.}, journal = {Current opinion in plant biology}, volume = {17}, number = {}, pages = {1-6}, doi = {10.1016/j.pbi.2013.09.004}, pmid = {24507487}, issn = {1879-0356}, mesh = {Algal Proteins/genetics ; Diploidy ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Haploidy ; Life Cycle Stages/*genetics ; *Mutation ; Phaeophyta/classification/*genetics/*growth & development ; Phylogeny ; }, abstract = {The life cycle of an organism is one of its fundamental features, influencing many aspects of its biology. The brown algae exhibit a diverse range of life cycles indicating that transitions between life cycle types may have been key adaptive events in the evolution of this group. Life cycle mutants, identified in the model organism Ectocarpus, are providing information about how life cycle progression is regulated at the molecular level in brown algae. We explore some of the implications of the phenotypes of the life cycle mutants described to date and draw comparisons with recent insights into life cycle regulation in the green lineage. Given the importance of coordinating growth and development with life cycle progression, we suggest that the co-option of ancient life cycle regulators to control key developmental events may be a common feature in diverse groups of multicellular eukaryotes.}, } @article {pmid24499792, year = {2014}, author = {Swer, PB and Bhadoriya, P and Saran, S}, title = {Analysis of Rheb in the cellular slime mold Dictyostelium discoideum: cellular localization, spatial expression and overexpression.}, journal = {Journal of biosciences}, volume = {39}, number = {1}, pages = {75-84}, pmid = {24499792}, issn = {0973-7138}, mesh = {Bacterial Proteins/metabolism ; Base Sequence ; Cluster Analysis ; DNA Primers/genetics ; Dictyostelium/*genetics/metabolism ; Gene Expression Profiling ; Immunoblotting ; In Situ Hybridization ; Luminescent Proteins/metabolism ; Molecular Sequence Data ; Monomeric GTP-Binding Proteins/*genetics/metabolism ; Neuropeptides/*genetics/metabolism ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Signal Transduction/genetics ; TOR Serine-Threonine Kinases/genetics/metabolism ; }, abstract = {Dictyostelium discoideum encodes a single Rheb protein showing sequence similarity to human homologues of Rheb. The DdRheb protein shares 52 percent identity and 100 percent similarity with the human Rheb1 protein. Fluorescence of Rheb yellow fluorescent protein fusion was detected in the D. discoideum cytoplasm. Reverse transcription-polymerase chain reaction and whole-mount in situ hybridization analyses showed that rheb is expressed at all stages of development and in prestalk cells in the multicellular structures developed. When the expression of rheb as a fusion with lacZ was driven under its own promoter, the beta-galactosidase activity was seen in the prestalk cells. D. discoideum overexpressing Rheb shows an increase in the size of the cell. Treatment of the overexpressing Rheb cells with rapamycin confirms its involvement in the TOR signalling pathway.}, } @article {pmid24498429, year = {2014}, author = {Kollmar, M and Hatje, K}, title = {Shared gene structures and clusters of mutually exclusive spliced exons within the metazoan muscle myosin heavy chain genes.}, journal = {PloS one}, volume = {9}, number = {2}, pages = {e88111}, pmid = {24498429}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Arthropods/*genetics ; Drosophila melanogaster/*genetics ; Exons/*genetics ; Molecular Sequence Data ; *Multigene Family ; Muscles/*metabolism ; Myosin Heavy Chains/*genetics ; Phylogeny ; RNA Splicing/*genetics ; Sequence Homology ; Sequence Homology, Amino Acid ; }, abstract = {Multicellular animals possess two to three different types of muscle tissues. Striated muscles have considerable ultrastructural similarity and contain a core set of proteins including the muscle myosin heavy chain (Mhc) protein. The ATPase activity of this myosin motor protein largely dictates muscle performance at the molecular level. Two different solutions to adjusting myosin properties to different muscle subtypes have been identified so far: Vertebrates and nematodes contain many independent differentially expressed Mhc genes while arthropods have single Mhc genes with clusters of mutually exclusive spliced exons (MXEs). The availability of hundreds of metazoan genomes now allowed us to study whether the ancient bilateria already contained MXEs, how MXE complexity subsequently evolved, and whether additional scenarios to control contractile properties in different muscles could be proposed, By reconstructing the Mhc genes from 116 metazoans we showed that all intron positions within the motor domain coding regions are conserved in all bilateria analysed. The last common ancestor of the bilateria already contained a cluster of MXEs coding for part of the loop-2 actin-binding sequence. Subsequently the protostomes and later the arthropods gained many further clusters while MXEs got completely lost independently in several branches (vertebrates and nematodes) and species (for example the annelid Helobdella robusta and the salmon louse Lepeophtheirus salmonis). Several bilateria have been found to encode multiple Mhc genes that might all or in part contain clusters of MXEs. Notable examples are a cluster of six tandemly arrayed Mhc genes, of which two contain MXEs, in the owl limpet Lottia gigantea and four Mhc genes with three encoding MXEs in the predatory mite Metaseiulus occidentalis. Our analysis showed that similar solutions to provide different myosin isoforms (multiple genes or clusters of MXEs or both) have independently been developed several times within bilaterian evolution.}, } @article {pmid24493248, year = {2014}, author = {Rajaram, H and Chaurasia, AK and Apte, SK}, title = {Cyanobacterial heat-shock response: role and regulation of molecular chaperones.}, journal = {Microbiology (Reading, England)}, volume = {160}, number = {Pt 4}, pages = {647-658}, doi = {10.1099/mic.0.073478-0}, pmid = {24493248}, issn = {1465-2080}, mesh = {Bacterial Proteins/metabolism ; Cyanobacteria/*physiology/*radiation effects ; *Gene Expression Regulation, Bacterial ; Heat-Shock Proteins/metabolism ; *Heat-Shock Response ; Molecular Chaperones/*metabolism ; }, abstract = {Cyanobacteria constitute a morphologically diverse group of oxygenic photoautotrophic microbes which range from unicellular to multicellular, and non-nitrogen-fixing to nitrogen-fixing types. Sustained long-term exposure to changing environmental conditions, during their three billion years of evolution, has presumably led to their adaptation to diverse ecological niches. The ability to maintain protein conformational homeostasis (folding-misfolding-refolding or aggregation-degradation) by molecular chaperones holds the key to the stress adaptability of cyanobacteria. Although cyanobacteria possess several genes encoding DnaK and DnaJ family proteins, these are not the most abundant heat-shock proteins (Hsps), as is the case in other bacteria. Instead, the Hsp60 family of proteins, comprising two phylogenetically conserved proteins, and small Hsps are more abundant during heat stress. The contribution of the Hsp100 (ClpB) family of proteins and of small Hsps in the unicellular cyanobacteria (Synechocystis and Synechococcus) as well as that of Hsp60 proteins in the filamentous cyanobacteria (Anabaena) to thermotolerance has been elucidated. The regulation of chaperone genes by several cis-elements and trans-acting factors has also been well documented. Recent studies have demonstrated novel transcriptional and translational (mRNA secondary structure) regulatory mechanisms in unicellular cyanobacteria. This article provides an insight into the heat-shock response: its organization, and ecophysiological regulation and role of molecular chaperones, in unicellular and filamentous nitrogen-fixing cyanobacterial strains.}, } @article {pmid24481194, year = {2013}, author = {Carter, LM and Kafsack, BF and Llinás, M and Mideo, N and Pollitt, LC and Reece, SE}, title = {Stress and sex in malaria parasites: Why does commitment vary?.}, journal = {Evolution, medicine, and public health}, volume = {2013}, number = {1}, pages = {135-147}, pmid = {24481194}, issn = {2050-6201}, support = {DP2 OD001315/OD/NIH HHS/United States ; R01 AI076276/AI/NIAID NIH HHS/United States ; }, abstract = {For vector-borne parasites such as malaria, how within- and between-host processes interact to shape transmission is poorly understood. In the host, malaria parasites replicate asexually but for transmission to occur, specialized sexual stages (gametocytes) must be produced. Despite the central role that gametocytes play in disease transmission, explanations of why parasites adjust gametocyte production in response to in-host factors remain controversial. We propose that evolutionary theory developed to explain variation in reproductive effort in multicellular organisms, provides a framework to understand gametocyte investment strategies. We examine why parasites adjust investment in gametocytes according to the impact of changing conditions on their in-host survival. We then outline experiments required to determine whether plasticity in gametocyte investment enables parasites to maintain fitness in a variable environment. Gametocytes are a target for anti-malarial transmission-blocking interventions so understanding plasticity in investment is central to maximizing the success of control measures in the face of parasite evolution.}, } @article {pmid24481180, year = {2013}, author = {Khan, SM and Reece, SE and Waters, AP and Janse, CJ and Kaczanowski, S}, title = {Why are male malaria parasites in such a rush?: Sex-specific evolution and host-parasite interactions.}, journal = {Evolution, medicine, and public health}, volume = {2013}, number = {1}, pages = {3-13}, pmid = {24481180}, issn = {2050-6201}, support = {083811//Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Disease-causing organisms are notorious for fast rates of molecular evolution and the ability to adapt rapidly to changes in their ecology. Sex plays a key role in evolution, and recent studies, in humans and other multicellular organisms, document that genes expressed principally or exclusively in males exhibit the fastest rates of adaptive evolution. However, despite the importance of sexual reproduction for many unicellular taxa, sex-biased gene expression and its evolutionary implications have been overlooked.

METHODS: We analyse genomic data from multiple malaria parasite (Plasmodium) species and proteomic data sets from different parasite life cycle stages.

RESULTS: The accelerated evolution of male-biased genes has only been examined in multicellular taxa, but our analyses reveal that accelerated evolution in genes with male-specific expression is also a feature of unicellular organisms. This 'fast-male' evolution is adaptive and likely facilitated by the male-biased sex ratio of gametes in the mating pool. Furthermore, we propose that the exceptional rates of evolution we observe are driven by interactions between males and host immune responses.

CONCLUSIONS: We reveal a novel form of host-parasite coevolution that enables parasites to evade host immune responses that negatively impact upon fertility. The identification of parasite genes with accelerated evolution has important implications for the identification of drug and vaccine targets. Specifically, vaccines targeting males will be more vulnerable to parasite evolution than those targeting females or both sexes.}, } @article {pmid24464418, year = {2014}, author = {Vijg, J}, title = {Aging genomes: a necessary evil in the logic of life.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {36}, number = {3}, pages = {282-292}, pmid = {24464418}, issn = {1521-1878}, support = {P01 AG017242/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*genetics ; Animals ; DNA Damage/genetics ; Genome/*genetics ; Humans ; *Life ; Mutation/genetics ; }, abstract = {Genomes are inherently unstable because of the need for DNA sequence variation as a substrate for evolution through natural selection. However, most multicellular organisms have postmitotic tissues, with limited opportunity for selective removal of cells harboring persistent damage and deleterious mutations, which can therefore contribute to functional decline, disease, and death. Key in this process is the role of genome maintenance, the network of protein products that repair DNA damage and signal DNA damage response pathways. Genome maintenance is beneficial early in life by swiftly eliminating DNA damage or damaged cells, facilitating rapid cell proliferation. However, at later ages accumulation of unrepaired damage and mutations, as well as ongoing cell depletion, promotes cancer, atrophy, and other deleterious effects associated with aging. As such, genome maintenance and its phenotypic sequelae provide yet another example of antagonistic pleiotropy in aging and longevity.}, } @article {pmid24463524, year = {2014}, author = {Jiang, C and Brown, PJ and Ducret, A and Brun, YV}, title = {Sequential evolution of bacterial morphology by co-option of a developmental regulator.}, journal = {Nature}, volume = {506}, number = {7489}, pages = {489-493}, pmid = {24463524}, issn = {1476-4687}, support = {F32 AI072992/AI/NIAID NIH HHS/United States ; S10 RR028697/RR/NCRR NIH HHS/United States ; GM051986/GM/NIGMS NIH HHS/United States ; S10RR028697-01/RR/NCRR NIH HHS/United States ; AI072992/AI/NIAID NIH HHS/United States ; R01 GM051986/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*cytology/*metabolism ; Bacterial Proteins/*metabolism ; *Biological Evolution ; Caulobacter crescentus/cytology/metabolism ; Caulobacteraceae/cytology/metabolism ; Cell Membrane/metabolism ; *Cell Polarity ; Evolution, Molecular ; Models, Biological ; Molecular Sequence Data ; Phylogeny ; Protein Transport ; }, abstract = {What mechanisms underlie the transitions responsible for the diverse shapes observed in the living world? Although bacteria exhibit a myriad of morphologies, the mechanisms responsible for the evolution of bacterial cell shape are not understood. We investigated morphological diversity in a group of bacteria that synthesize an appendage-like extension of the cell envelope called the stalk. The location and number of stalks varies among species, as exemplified by three distinct subcellular positions of stalks within a rod-shaped cell body: polar in the genus Caulobacter and subpolar or bilateral in the genus Asticcacaulis. Here we show that a developmental regulator of Caulobacter crescentus, SpmX, is co-opted in the genus Asticcacaulis to specify stalk synthesis either at the subpolar or bilateral positions. We also show that stepwise evolution of a specific region of SpmX led to the gain of a new function and localization of this protein, which drove the sequential transition in stalk positioning. Our results indicate that changes in protein function, co-option and modularity are key elements in the evolution of bacterial morphology. Therefore, similar evolutionary principles of morphological transitions apply to both single-celled prokaryotes and multicellular eukaryotes.}, } @article {pmid24462754, year = {2014}, author = {Wang, N and Yue, Z and Liang, D and Ma, F}, title = {Genome-wide identification of members in the YTH domain-containing RNA-binding protein family in apple and expression analysis of their responsiveness to senescence and abiotic stresses.}, journal = {Gene}, volume = {538}, number = {2}, pages = {292-305}, doi = {10.1016/j.gene.2014.01.039}, pmid = {24462754}, issn = {1879-0038}, mesh = {Chromosome Mapping ; Expressed Sequence Tags ; Gene Duplication ; Gene Expression ; *Genes, Plant ; Genome, Plant ; Malus/*genetics/*metabolism ; Models, Genetic ; Models, Molecular ; Multigene Family ; Phylogeny ; Plant Proteins/chemistry/*genetics/*metabolism ; Protein Structure, Tertiary ; RNA-Binding Proteins/chemistry/*genetics/*metabolism ; Stress, Physiological ; Synteny ; }, abstract = {YT521-homology (YTH) domain-containing RNA-binding proteins (YTPs) are a small gene family involved in post-transcriptional regulation. We identified 26 putative YTP gene models in the apple genome. Although plant YTPs have been classified into three groups, those in multi-cellular organisms belong only to Groups A and B. The apple genome contains 22 YTP gene models in Group A and four in Group B. Duplication analysis showed that tandem and segmental duplications contributed only partially to an expansion in apple YTP numbers. YTH was the only recognizable domain in apple YTPs; its three-dimensional structure implied possible motifs for RNA-binding. After the assembly of expressed sequence tags (ESTs) and gene-cloning, we were able to identify 14 apple YTPs that were expressed in various tissues, especially senescing leaves. Expression analysis showed that these YTPs also responded to several abiotic stresses. Taken together, our genome-wide evaluation provides new insight for further research on the effects of those stresses.}, } @article {pmid24462003, year = {2014}, author = {Ghisalberti, M and Gold, DA and Laflamme, M and Clapham, ME and Narbonne, GM and Summons, RE and Johnston, DT and Jacobs, DK}, title = {Canopy flow analysis reveals the advantage of size in the oldest communities of multicellular eukaryotes.}, journal = {Current biology : CB}, volume = {24}, number = {3}, pages = {305-309}, pmid = {24462003}, issn = {1879-0445}, support = {T32 HG002536/HG/NHGRI NIH HHS/United States ; T32HG002536/HG/NHGRI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Eukaryota/*physiology ; }, abstract = {At Mistaken Point, Newfoundland, Canada, rangeomorph "fronds" dominate the earliest (579-565 million years ago) fossil communities of large (0.1 to 2 m height) multicellular benthic eukaryotes. They lived in low-flow environments, fueled by uptake [1-3] of dissolved reactants (osmotrophy). However, prokaryotes are effective osmotrophs, and the advantage of taller eukaryotic osmotrophs in this deep-water community context has not been addressed. We reconstructed flow-velocity profiles and vertical mixing using canopy flow models appropriate to the densities of the observed communities. Further modeling of processes at organismal surfaces documents increasing uptake with height in the community as a function of thinning of the diffusive boundary layer with increased velocity. The velocity profile, produced by canopy flow in the community, generates this advantage of upward growth. Alternative models of upward growth advantage based on redox/resource gradients fail, given the efficiency of vertical mixing. In benthic communities of osmotrophs of sufficient density, access to flow in low-flow settings provides an advantage to taller architecture, providing a selectional driver for communities of tall eukaryotes in contexts where phototropism cannot contribute to upward growth. These Ediacaran deep-sea fossils were preserved during the increasing oxygenation prior to the Cambrian radiation of animals and likely represent an important phase in the ecological and evolutionary transition to more complex eukaryotic forms.}, } @article {pmid24454845, year = {2014}, author = {Tamura, A and Yamada, N and Yaguchi, Y and Machida, Y and Mori, I and Osanai, M}, title = {Both neurons and astrocytes exhibited tetrodotoxin-resistant metabotropic glutamate receptor-dependent spontaneous slow Ca2+ oscillations in striatum.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e85351}, pmid = {24454845}, issn = {1932-6203}, mesh = {Animals ; Astrocytes/drug effects/metabolism/*physiology ; Calcium/*metabolism ; Corpus Striatum/drug effects/metabolism/*physiology ; Green Fluorescent Proteins/genetics ; Mice ; Mice, Transgenic ; Neurons/drug effects/metabolism/*physiology ; Receptors, Metabotropic Glutamate/*drug effects/*metabolism ; Tetrodotoxin/*pharmacology ; }, abstract = {The striatum plays an important role in linking cortical activity to basal ganglia outputs. Group I metabotropic glutamate receptors (mGluRs) are densely expressed in the medium spiny projection neurons and may be a therapeutic target for Parkinson's disease. The group I mGluRs are known to modulate the intracellular Ca(2+) signaling. To characterize Ca(2+) signaling in striatal cells, spontaneous cytoplasmic Ca(2+) transients were examined in acute slice preparations from transgenic mice expressing green fluorescent protein (GFP) in the astrocytes. In both the GFP-negative cells (putative-neurons) and astrocytes of the striatum, spontaneous slow and long-lasting intracellular Ca(2+) transients (referred to as slow Ca(2+) oscillations), which lasted up to approximately 200 s, were found. Neither the inhibition of action potentials nor ionotropic glutamate receptors blocked the slow Ca(2+) oscillation. Depletion of the intracellular Ca(2+) store and the blockade of inositol 1,4,5-trisphosphate receptors greatly reduced the transient rate of the slow Ca(2+) oscillation, and the application of an antagonist against mGluR5 also blocked the slow Ca(2+) oscillation in both putative-neurons and astrocytes. Thus, the mGluR5-inositol 1,4,5-trisphosphate signal cascade is the primary contributor to the slow Ca(2+) oscillation in both putative-neurons and astrocytes. The slow Ca(2+) oscillation features multicellular synchrony, and both putative-neurons and astrocytes participate in the synchronous activity. Therefore, the mGluR5-dependent slow Ca(2+) oscillation may involve in the neuron-glia interaction in the striatum.}, } @article {pmid24451992, year = {2014}, author = {Benton, MA and Pavlopoulos, A}, title = {Tribolium embryo morphogenesis: may the force be with you.}, journal = {Bioarchitecture}, volume = {4}, number = {1}, pages = {16-21}, pmid = {24451992}, issn = {1949-100X}, mesh = {Animals ; Tribolium/*embryology ; }, abstract = {Development of multicellular organisms depends on patterning and growth mechanisms encoded in the genome, but also on the physical properties and mechanical interactions of the constituent cells that interpret these genetic cues. This fundamental biological problem requires integrated studies at multiple levels of biological organization: from genes, to cell behaviors, to tissue morphogenesis. We have recently combined functional genetics with live imaging approaches in embryos of the insect Tribolium castaneum, in order to understand their remarkable transformation from a uniform single-layered blastoderm into a condensed multi-layered embryo covered by extensive extra-embryonic tissues. We first developed a quick and reliable methodology to fluorescently label various cell components in entire Tribolium embryos. Live imaging of labeled embryos at single cell resolution provided detailed descriptions of cell behaviors and tissue movements during normal embryogenesis. We then compared cell and tissue dynamics between wild-type and genetically perturbed embryos that exhibited altered relative proportions of constituent tissues. This systematic comparison led to a qualitative model of the molecular, cellular and tissue interactions that orchestrate the observed epithelial rearrangements. We expect this work to establish the Tribolium embryo as a powerful and attractive model system for biologists and biophysicists interested in the molecular, cellular and mechanical control of tissue morphogenesis.}, } @article {pmid24448446, year = {2014}, author = {Ninova, M and Ronshaugen, M and Griffiths-Jones, S}, title = {Fast-evolving microRNAs are highly expressed in the early embryo of Drosophila virilis.}, journal = {RNA (New York, N.Y.)}, volume = {20}, number = {3}, pages = {360-372}, pmid = {24448446}, issn = {1469-9001}, support = {/WT_/Wellcome Trust/United Kingdom ; BB/H017801/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Base Sequence ; Conserved Sequence ; Drosophila/classification/*genetics/growth & development ; Embryo, Nonmammalian/cytology/metabolism ; *Evolution, Molecular ; Female ; *Gene Expression Regulation, Developmental ; In Situ Hybridization ; MicroRNAs/*genetics ; Molecular Sequence Data ; Phylogeny ; Sequence Homology, Nucleic Acid ; }, abstract = {MicroRNAs are short non-protein-coding RNAs that regulate gene expression at the post-transcriptional level and are essential for the embryonic development of multicellular animals. Comparative genome-scale analyses have revealed that metazoan evolution is accompanied by the continuous acquisition of novel microRNA genes. This suggests that novel microRNAs may promote innovation and diversity in development. We determined the evolutionary origins of extant Drosophila microRNAs and estimated the sequence divergence between the 130 orthologous microRNAs in Drosophila melanogaster and Drosophila virilis, separated by 63 million years of evolution. We then generated small RNA sequencing data sets covering D. virilis development and explored the relationship between microRNA conservation and expression in a developmental context. We find that late embryonic, larval, and adult stages are dominated by conserved microRNAs. This pattern, however, does not hold for the early embryo, where rapidly evolving microRNAs are uniquely present at high levels in both species. The group of fast-evolving microRNAs that are highly expressed in the early embryo belong to two Drosophilid lineage-specific clusters: mir-310 ∼ 313 and mir-309 ∼ 6. These clusters have particularly complex evolutionary histories of duplication, gain, and loss. Our analyses suggest that the early embryo is a more permissive environment for microRNA changes and innovations. Fast-evolving microRNAs, therefore, have the opportunity to become preferentially integrated in early developmental processes, and may impact the evolution of development. The relationship between microRNA conservation and expression throughout the development of Drosophila differs from that previously observed for protein-coding genes.}, } @article {pmid24443438, year = {2014}, author = {Sebé-Pedrós, A and Grau-Bové, X and Richards, TA and Ruiz-Trillo, I}, title = {Evolution and classification of myosins, a paneukaryotic whole-genome approach.}, journal = {Genome biology and evolution}, volume = {6}, number = {2}, pages = {290-305}, pmid = {24443438}, issn = {1759-6653}, support = {206883/ERC_/European Research Council/International ; BB/G00885X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/G00885X/2/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Eukaryota/chemistry/*classification/*genetics ; *Evolution, Molecular ; *Genome ; Myosins/chemistry/*genetics ; Phylogeny ; Protein Structure, Tertiary ; }, abstract = {Myosins are key components of the eukaryotic cytoskeleton, providing motility for a broad diversity of cargoes. Therefore, understanding the origin and evolutionary history of myosin classes is crucial to address the evolution of eukaryote cell biology. Here, we revise the classification of myosins using an updated taxon sampling that includes newly or recently sequenced genomes and transcriptomes from key taxa. We performed a survey of eukaryotic genomes and phylogenetic analyses of the myosin gene family, reconstructing the myosin toolkit at different key nodes in the eukaryotic tree of life. We also identified the phylogenetic distribution of myosin diversity in terms of number of genes, associated protein domains and number of classes in each taxa. Our analyses show that new classes (i.e., paralogs) and domain architectures were continuously generated throughout eukaryote evolution, with a significant expansion of myosin abundance and domain architectural diversity at the stem of Holozoa, predating the origin of animal multicellularity. Indeed, single-celled holozoans have the most complex myosin complement among eukaryotes, with paralogs of most myosins previously considered animal specific. We recover a dynamic evolutionary history, with several lineage-specific expansions (e.g., the myosin III-like gene family diversification in choanoflagellates), convergence in protein domain architectures (e.g., fungal and animal chitin synthase myosins), and important secondary losses. Overall, our evolutionary scheme demonstrates that the ancestral eukaryote likely had a complex myosin repertoire that included six genes with different protein domain architectures. Finally, we provide an integrative and robust classification, useful for future genomic and functional studies on this crucial eukaryotic gene family.}, } @article {pmid24440719, year = {2014}, author = {Heyn, P and Kircher, M and Dahl, A and Kelso, J and Tomancak, P and Kalinka, AT and Neugebauer, KM}, title = {The earliest transcribed zygotic genes are short, newly evolved, and different across species.}, journal = {Cell reports}, volume = {6}, number = {2}, pages = {285-292}, doi = {10.1016/j.celrep.2013.12.030}, pmid = {24440719}, issn = {2211-1247}, mesh = {Animals ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Genes, Mitochondrial ; RNA, Messenger/genetics/metabolism ; Species Specificity ; *Transcription, Genetic ; Zebrafish ; Zygote/*metabolism ; }, abstract = {The transition from maternal to zygotic control is fundamental to the life cycle of all multicellular organisms. It is widely believed that genomes are transcriptionally inactive from fertilization until zygotic genome activation (ZGA). Thus, the earliest genes expressed probably support the rapid cell divisions that precede morphogenesis and, if so, might be evolutionarily conserved. Here, we identify the earliest zygotic transcripts in the zebrafish, Danio rerio, through metabolic labeling and purification of RNA from staged embryos. Surprisingly, the mitochondrial genome was highly active from the one-cell stage onwards, showing that significant transcriptional activity exists at fertilization. We show that 592 nuclear genes become active when cell cycles are still only 15 min long, confining expression to relatively short genes. Furthermore, these zygotic genes are evolutionarily younger than those expressed at other developmental stages. Comparison of fish, fly, and mouse data revealed different sets of genes expressed at ZGA. This species specificity uncovers an evolutionary plasticity in early embryogenesis that probably confers substantial adaptive potential.}, } @article {pmid24440400, year = {2014}, author = {Mikhail, AS and Eetezadi, S and Ekdawi, SN and Stewart, J and Allen, C}, title = {Image-based analysis of the size- and time-dependent penetration of polymeric micelles in multicellular tumor spheroids and tumor xenografts.}, journal = {International journal of pharmaceutics}, volume = {464}, number = {1-2}, pages = {168-177}, doi = {10.1016/j.ijpharm.2014.01.010}, pmid = {24440400}, issn = {1873-3476}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Female ; HT29 Cells ; HeLa Cells ; Humans ; Mice ; Mice, Nude ; *Micelles ; Microscopy, Electron, Transmission/*methods ; Particle Size ; Polymers/chemistry/*metabolism ; Spheroids, Cellular/*metabolism/pathology/ultrastructure ; Time Factors ; Xenograft Model Antitumor Assays/*methods ; }, abstract = {While the heightened tumor accumulation of systemically administered nanomedicines relative to conventional chemotherapeutic agents has been well established, corresponding improvements in therapeutic efficacy have often been incommensurate. This observation may be attributed to the limited exposure of cancer cells to therapy due to the heterogeneous intratumoral distribution and poor interstitial penetration of nanoparticle-based drug delivery systems. In the present work, the spatio-temporal distribution of block copolymer micelles (BCMs) of different sizes was evaluated in multicellular tumor spheroids (MCTS) and tumor xenografts originating from human cervical (HeLa) and colon (HT29) cancer cells using image-based, computational techniques. Micelle penetration was found to depend on nanoparticle size, time as well as tumor and spheroid cell line. Moreover, spheroids demonstrated the capacity to predict relative trends in nanoparticle interstitial transport in tumor xenografts. Overall, techniques are presented for the assessment of nanoparticle distribution in spheroids and xenografts and used to evaluate the influence of micelle size and cell-line specific tissue properties on micelle interstitial penetration.}, } @article {pmid24429898, year = {2014}, author = {Sun, Y and Yang, X and Wang, Q}, title = {In-silico analysis on biofabricating vascular networks using kinetic Monte Carlo simulations.}, journal = {Biofabrication}, volume = {6}, number = {1}, pages = {015008}, doi = {10.1088/1758-5082/6/1/015008}, pmid = {24429898}, issn = {1758-5090}, mesh = {Algorithms ; Bioprinting ; Cell Aggregation ; Cells/*chemistry/cytology ; Computer Simulation ; Kinetics ; Monte Carlo Method ; Tissue Engineering/*instrumentation ; Tissue Scaffolds/*chemistry ; }, abstract = {We present a computational modeling approach to study the fusion of multicellular aggregate systems in a novel scaffold-less biofabrication process, known as 'bioprinting'. In this novel technology, live multicellular aggregates are used as fundamental building blocks to make tissues or organs (collectively known as the bio-constructs,) via the layer-by-layer deposition technique or other methods; the printed bio-constructs embedded in maturogens, consisting of nutrient-rich bio-compatible hydrogels, are then placed in bioreactors to undergo the cellular aggregate fusion process to form the desired functional bio-structures. Our approach reported here is an agent-based modeling method, which uses the kinetic Monte Carlo (KMC) algorithm to evolve the cellular system on a lattice. In this method, the cells and the hydrogel media, in which cells are embedded, are coarse-grained to material's points on a three-dimensional (3D) lattice, where the cell-cell and cell-medium interactions are quantified by adhesion and cohesion energies. In a multicellular aggregate system with a fixed number of cells and fixed amount of hydrogel media, where the effect of cell differentiation, proliferation and death are tactically neglected, the interaction energy is primarily dictated by the interfacial energy between cell and cell as well as between cell and medium particles on the lattice, respectively, based on the differential adhesion hypothesis. By using the transition state theory to track the time evolution of the multicellular system while minimizing the interfacial energy, KMC is shown to be an efficient time-dependent simulation tool to study the evolution of the multicellular aggregate system. In this study, numerical experiments are presented to simulate fusion and cell sorting during the biofabrication process of vascular networks, in which the bio-constructs are fabricated via engineering designs. The results predict the feasibility of fabricating the vascular structures via the bioprinting technology and demonstrate the morphological development process during cellular aggregate fusion in various engineering designed structures. The study also reveals that cell sorting will perhaps not significantly impact the final fabricated products, should the maturation process be well-controlled in bioprinting.}, } @article {pmid24418530, year = {2014}, author = {Chen, IC and Griesenauer, B and Yu, YT and Velicer, GJ}, title = {A recent evolutionary origin of a bacterial small RNA that controls multicellular fruiting body development.}, journal = {Molecular phylogenetics and evolution}, volume = {73}, number = {}, pages = {1-9}, doi = {10.1016/j.ympev.2014.01.001}, pmid = {24418530}, issn = {1095-9513}, support = {R01 GM079690/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Base Sequence ; *Evolution, Molecular ; Genetic Variation/genetics ; Molecular Sequence Data ; Myxococcus xanthus/classification/*genetics/*physiology ; Nucleic Acid Conformation ; *Phylogeny ; RNA, Bacterial/chemistry/*genetics ; RNA, Small Untranslated/chemistry/*genetics ; Spores, Bacterial/*genetics/growth & development ; }, abstract = {In animals and plants, non-coding small RNAs regulate the expression of many genes at the post-transcriptional level. Recently, many non-coding small RNAs (sRNAs) have also been found to regulate a variety of important biological processes in bacteria, including social traits, but little is known about the phylogenetic or mechanistic origins of such bacterial sRNAs. Here we propose a phylogenetic origin of the myxobacterial sRNA Pxr, which negatively regulates the initiation of fruiting body development in Myxococcus xanthus as a function of nutrient level, and also examine its diversification within the Myxococcocales order. Homologs of pxr were found throughout the Cystobacterineae suborder (with a few possible losses) but not outside this clade, suggesting a single origin of the Pxr regulatory system in the basal Cystobacterineae lineage. Rates of pxr sequence evolution varied greatly across Cystobacterineae sub-clades in a manner not predicted by overall genome divergence. A single copy of pxr was found in most species with 17% of nucleotide positions being polymorphic among them. However three tandem paralogs were present within the genus Cystobacter and these alleles together exhibited an elevated rate of divergence. There appears to have been strong selection for maintenance of a predicted stem-loop structure, as polymorphisms accumulated preferentially at loop or bulge regions or as complementary substitutions within predicted stems. All detected pxr homologs are located in the intergenic region between the σ(54)-dependent response regulator nla19 and a predicted NADH dehydrogenase gene, but other neighboring gene content has diversified.}, } @article {pmid24417348, year = {2014}, author = {Maciak, S and Bonda-Ostaszewska, E and Czarnołęski, M and Konarzewski, M and Kozłowski, J}, title = {Mice divergently selected for high and low basal metabolic rates evolved different cell size and organ mass.}, journal = {Journal of evolutionary biology}, volume = {27}, number = {3}, pages = {478-487}, doi = {10.1111/jeb.12306}, pmid = {24417348}, issn = {1420-9101}, mesh = {Animals ; *Basal Metabolism ; *Cell Size ; Male ; Mice ; *Organ Size ; }, abstract = {Evolution of metabolic rates of multicellular organisms is hypothesized to reflect the evolution of their cell architecture. This is likely to stem from a tight link between the sizes of cells and nuclei, which are expected to be inversely related to cell metabolism. Here, we analysed basal metabolic rate (BMR), internal organ masses and the cell/nucleus size in different tissues of laboratory mice divergently selected for high/low mass-corrected BMR and four random-bred mouse lines. Random-bred lines had intermediate levels of BMR as compared to low- and high-BMR lines. Yet, this pattern was only partly consistent with the between-line differences in cell/nucleus sizes. Erythrocytes and skin epithelium cells were smaller in the high-BMR line than in other lines, but the cells of low-BMR and random-bred mice were similar in size. On the other hand, the size of hepatocytes, kidney proximal tubule cells and duodenum enterocytes were larger in high-BMR mice than other lines. All cell and nucleus sizes were positively correlated, which supports the role of the nucleus in cell size regulation. Our results suggest that the evolution of high BMR involves a reduction in cell size in specialized tissues, whose functions are primarily dictated by surface-to-volume ratios, such as erythrocytes. High BMR may, however, also incur an increase in cell size in tissues with an intense transcription and translation, such as hepatocytes.}, } @article {pmid24410880, year = {2014}, author = {Ludeman, DA and Farrar, N and Riesgo, A and Paps, J and Leys, SP}, title = {Evolutionary origins of sensation in metazoans: functional evidence for a new sensory organ in sponges.}, journal = {BMC evolutionary biology}, volume = {14}, number = {}, pages = {3}, pmid = {24410880}, issn = {1471-2148}, mesh = {Animals ; *Biological Evolution ; Cilia/genetics/*physiology ; Phylogeny ; Porifera/classification/genetics/*physiology ; Sensation ; }, abstract = {BACKGROUND: One of the hallmarks of multicellular organisms is the ability of their cells to trigger responses to the environment in a coordinated manner. In recent years primary cilia have been shown to be present as 'antennae' on almost all animal cells, and are involved in cell-to-cell signaling in development and tissue homeostasis; how this sophisticated sensory system arose has been little-studied and its evolution is key to understanding how sensation arose in the Animal Kingdom. Sponges (Porifera), one of the earliest evolving phyla, lack conventional muscles and nerves and yet sense and respond to changes in their fluid environment. Here we demonstrate the presence of non-motile cilia in sponges and studied their role as flow sensors.

RESULTS: Demosponges excrete wastes from their body with a stereotypic series of whole-body contractions using a structure called the osculum to regulate the water-flow through the body. In this study we show that short cilia line the inner epithelium of the sponge osculum. Ultrastructure of the cilia shows an absence of a central pair of microtubules and high speed imaging shows they are non-motile, suggesting they are not involved in generating flow. In other animals non-motile, 'primary', cilia are involved in sensation. Here we show that molecules known to block cationic ion channels in primary cilia and which inhibit sensory function in other organisms reduce or eliminate sponge contractions. Removal of the cilia using chloral hydrate, or removal of the whole osculum, also stops the contractions; in all instances the effect is reversible, suggesting that the cilia are involved in sensation. An analysis of sponge transcriptomes shows the presence of several transient receptor potential (TRP) channels including PKD channels known to be involved in sensing changes in flow in other animals. Together these data suggest that cilia in sponge oscula are involved in flow sensation and coordination of simple behaviour.

CONCLUSIONS: This is the first evidence of arrays of non-motile cilia in sponge oscula. Our findings provide support for the hypothesis that the cilia are sensory, and if true, the osculum may be considered a sensory organ that is used to coordinate whole animal responses in sponges. Arrays of primary cilia like these could represent the first step in the evolution of sensory and coordination systems in metazoans.}, } @article {pmid24398598, year = {2014}, author = {Sharma, M and Singh, A and Shankar, A and Pandey, A and Baranwal, V and Kapoor, S and Tyagi, AK and Pandey, GK}, title = {Comprehensive expression analysis of rice Armadillo gene family during abiotic stress and development.}, journal = {DNA research : an international journal for rapid publication of reports on genes and genomes}, volume = {21}, number = {3}, pages = {267-283}, pmid = {24398598}, issn = {1756-1663}, mesh = {Armadillo Domain Proteins/*genetics/metabolism ; Chromosomes, Plant ; Computational Biology ; Evolution, Molecular ; Gene Duplication ; Gene Expression Profiling ; Genome, Plant ; Microarray Analysis ; Multigene Family ; Oryza/*genetics/growth & development/metabolism ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Promoter Regions, Genetic ; Stress, Physiological ; }, abstract = {Genes in the Armadillo (ARM)-repeat superfamily encode proteins with a range of developmental and physiological processes in unicellular and multicellular eukaryotes. These 42 amino acid, long tandem repeat-containing proteins have been abundantly recognized in many plant species. Previous studies have confirmed that Armadillo proteins constitute a multigene family in Arabidopsis. In this study, we performed a computational analysis in the rice genome (Oryza sativa L. subsp. japonica), and identified 158 genes of Armadillo superfamily. Phylogenetic study classified them into several arbitrary groups based on a varying number of non-conserved ARM repeats and accessory domain(s) associated with them. An in-depth analysis of gene expression through microarray and Q-PCR revealed a number of ARM proteins expressing differentially in abiotic stresses and developmental conditions, suggesting a potential roles of this superfamily in development and stress signalling. Comparative phylogenetic analysis between Arabidopsis and rice Armadillo genes revealed a high degree of evolutionary conservation between the orthologues in two plant species. The non-synonymous and synonymous substitutions per site ratios (Ka/Ks) of duplicated gene pairs indicate a purifying selection. This genome-wide identification and expression analysis provides a basis for further functional analysis of Armadillo genes under abiotic stress and reproductive developmental condition in the plant lineage.}, } @article {pmid24384602, year = {2014}, author = {Claessen, D and Rozen, DE and Kuipers, OP and Søgaard-Andersen, L and van Wezel, GP}, title = {Bacterial solutions to multicellularity: a tale of biofilms, filaments and fruiting bodies.}, journal = {Nature reviews. Microbiology}, volume = {12}, number = {2}, pages = {115-124}, pmid = {24384602}, issn = {1740-1534}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Apoptosis ; Bacteria/cytology/*growth & development ; *Bacterial Physiological Phenomena ; Biofilms/*growth & development ; Biological Evolution ; Cell Division ; Cell Transdifferentiation ; Cytoskeleton ; Signal Transduction ; Spores, Bacterial ; }, abstract = {Although bacteria frequently live as unicellular organisms, many spend at least part of their lives in complex communities, and some have adopted truly multicellular lifestyles and have abandoned unicellular growth. These transitions to multicellularity have occurred independently several times for various ecological reasons, resulting in a broad range of phenotypes. In this Review, we discuss the strategies that are used by bacteria to form and grow in multicellular structures that have hallmark features of multicellularity, including morphological differentiation, programmed cell death and patterning. In addition, we examine the evolutionary and ecological factors that lead to the wide range of coordinated multicellular behaviours that are observed in bacteria.}, } @article {pmid24384569, year = {2014}, author = {Knoll, AH}, title = {Paleobiological perspectives on early eukaryotic evolution.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {6}, number = {1}, pages = {}, pmid = {24384569}, issn = {1943-0264}, mesh = {Animals ; *Biological Evolution ; *Fossils ; *Paleontology ; }, abstract = {Eukaryotic organisms radiated in Proterozoic oceans with oxygenated surface waters, but, commonly, anoxia at depth. Exceptionally preserved fossils of red algae favor crown group emergence more than 1200 million years ago, but older (up to 1600-1800 million years) microfossils could record stem group eukaryotes. Major eukaryotic diversification ~800 million years ago is documented by the increase in the taxonomic richness of complex, organic-walled microfossils, including simple coenocytic and multicellular forms, as well as widespread tests comparable to those of extant testate amoebae and simple foraminiferans and diverse scales comparable to organic and siliceous scales formed today by protists in several clades. Mid-Neoproterozoic establishment or expansion of eukaryophagy provides a possible mechanism for accelerating eukaryotic diversification long after the origin of the domain. Protists continued to diversify along with animals in the more pervasively oxygenated oceans of the Phanerozoic Eon.}, } @article {pmid24381582, year = {2013}, author = {Boucher, B and Jenna, S}, title = {Genetic interaction networks: better understand to better predict.}, journal = {Frontiers in genetics}, volume = {4}, number = {}, pages = {290}, pmid = {24381582}, issn = {1664-8021}, abstract = {A genetic interaction (GI) between two genes generally indicates that the phenotype of a double mutant differs from what is expected from each individual mutant. In the last decade, genome scale studies of quantitative GIs were completed using mainly synthetic genetic array technology and RNA interference in yeast and Caenorhabditis elegans. These studies raised questions regarding the functional interpretation of GIs, the relationship of genetic and molecular interaction networks, the usefulness of GI networks to infer gene function and co-functionality, the evolutionary conservation of GI, etc. While GIs have been used for decades to dissect signaling pathways in genetic models, their functional interpretations are still not trivial. The existence of a GI between two genes does not necessarily imply that these two genes code for interacting proteins or that the two genes are even expressed in the same cell. In fact, a GI only implies that the two genes share a functional relationship. These two genes may be involved in the same biological process or pathway; or they may also be involved in compensatory pathways with unrelated apparent function. Considering the powerful opportunity to better understand gene function, genetic relationship, robustness and evolution, provided by a genome-wide mapping of GIs, several in silico approaches have been employed to predict GIs in unicellular and multicellular organisms. Most of these methods used weighted data integration. In this article, we will review the later knowledge acquired on GI networks in metazoans by looking more closely into their relationship with pathways, biological processes and molecular complexes but also into their modularity and organization. We will also review the different in silico methods developed to predict GIs and will discuss how the knowledge acquired on GI networks can be used to design predictive tools with higher performances.}, } @article {pmid25904998, year = {2014}, author = {Schilde, C and Skiba, A and Schaap, P}, title = {Evolutionary reconstruction of pattern formation in 98 Dictyostelium species reveals that cell-type specialization by lateral inhibition is a derived trait.}, journal = {EvoDevo}, volume = {5}, number = {}, pages = {34}, pmid = {25904998}, issn = {2041-9139}, support = {BB/D013453/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/G020426/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Multicellularity provides organisms with opportunities for cell-type specialization, but requires novel mechanisms to position correct proportions of different cell types throughout the organism. Dictyostelid social amoebas display an early form of multicellularity, where amoebas aggregate to form fruiting bodies, which contain only spores or up to four additional cell-types. These cell types will form the stalk and support structures for the stalk and spore head. Phylogenetic inference subdivides Dictyostelia into four major groups, with the model organism D. discoideum residing in group 4. In D. discoideum differentiation of its five cell types is dominated by lateral inhibition-type mechanisms that trigger scattered cell differentiation, with tissue patterns being formed by cell sorting.

RESULTS: To reconstruct the evolution of pattern formation in Dictyostelia, we used cell-type specific antibodies and promoter-reporter fusion constructs to investigate pattern formation in 98 species that represent all groupings. Our results indicate that in all early diverging Dictyostelia and most members of groups 1-3, cells differentiate into maximally two cell types, prestalk and prespore cells, with pattern formation being dominated by position-dependent transdifferentiation of prespore cells into prestalk cells. In clade 2A, prestalk and stalk cell differentiation are lost and the prespore cells construct an acellular stalk. Group 4 species set aside correct proportions of prestalk and prespore cells early in development, and differentiate into up to three more supporting cell types.

CONCLUSIONS: Our experiments show that positional transdifferentiation is the ancestral mode of pattern formation in Dictyostelia. The early specification of a prestalk population equal to the number of stalk cells is a derived trait that emerged in group 4 and a few late diverging species in the other groups. Group 4 spore masses are larger than those of other groups and the differentiation of supporting cell types by lateral inhibition may have facilitated this increase in size. The signal DIF-1, which is secreted by prespore cells, triggers differentiation of supporting cell types. The synthesis and degradation of DIF-1 were shown to be restricted to group 4. This suggests that the emergence of DIF-1 signalling caused increased cell-type specialization in this group.}, } @article {pmid24378600, year = {2014}, author = {Gamazon, ER and Stranger, BE}, title = {Genomics of alternative splicing: evolution, development and pathophysiology.}, journal = {Human genetics}, volume = {133}, number = {6}, pages = {679-687}, pmid = {24378600}, issn = {1432-1203}, mesh = {*Alternative Splicing ; Biological Evolution ; Databases, Genetic ; Genetic Therapy ; Genetic Variation ; *Genome, Human ; Genomics ; Humans ; Muscular Dystrophy, Duchenne/*genetics/physiopathology/therapy ; Myelodysplastic Syndromes/*genetics/physiopathology/therapy ; Oligonucleotides, Antisense/therapeutic use ; *Software ; Transcriptome ; beta-Thalassemia/*genetics/physiopathology/therapy ; }, abstract = {Alternative splicing is a major cellular mechanism in metazoans for generating proteomic diversity. A large proportion of protein-coding genes in multicellular organisms undergo alternative splicing, and in humans, it has been estimated that nearly 90 % of protein-coding genes-much larger than expected-are subject to alternative splicing. Genomic analyses of alternative splicing have illuminated its universal role in shaping the evolution of genomes, in the control of developmental processes, and in the dynamic regulation of the transcriptome to influence phenotype. Disruption of the splicing machinery has been found to drive pathophysiology, and indeed reprogramming of aberrant splicing can provide novel approaches to the development of molecular therapy. This review focuses on the recent progress in our understanding of alternative splicing brought about by the unprecedented explosive growth of genomic data and highlights the relevance of human splicing variation on disease and therapy.}, } @article {pmid24369344, year = {2014}, author = {Li, J and Wu, Y and Qi, Y}, title = {MicroRNAs in a multicellular green alga Volvox carteri.}, journal = {Science China. Life sciences}, volume = {57}, number = {1}, pages = {36-45}, doi = {10.1007/s11427-013-4580-3}, pmid = {24369344}, issn = {1869-1889}, mesh = {Base Sequence ; Blotting, Northern ; MicroRNAs/*genetics ; Molecular Sequence Data ; Reverse Transcriptase Polymerase Chain Reaction ; Volvox/*genetics ; }, abstract = {microRNAs (miRNAs) have emerged as key components in the eukaryotic gene regulatory network. We and others have previously identified many miRNAs in a unicellular green alga, Chlamydomonas reinhardtii. To investigate whether miRNA-mediated gene regulation is a general mechanism in green algae and how miRNAs have been evolved in the green algal lineage, we examined small RNAs in Volvox carteri, a multicellular species in the same family with Chlamydomonas reinhardtii. We identified 174 miRNAs in Volvox, with many of them being highly enriched in gonidia or somatic cells. The targets of the miRNAs were predicted and many of them were subjected to miRNA-mediated cleavage in vivo, suggesting that miRNAs play regulatory roles in the biology of green algae. Our catalog of miRNAs and their targets provides a resource for further studies on the evolution, biological functions, and genomic properties of miRNAs in green algae.}, } @article {pmid24368736, year = {2013}, author = {Olson, BJ}, title = {Multicellularity: From brief encounters to lifelong unions.}, journal = {eLife}, volume = {2}, number = {}, pages = {e01893}, pmid = {24368736}, issn = {2050-084X}, mesh = {Amoeba/*physiology ; *Cell Division ; *Evolution, Molecular ; }, abstract = {Could the transient aggregation of unicellular organisms have paved the way for the evolution of the multicellular animals?}, } @article {pmid24368732, year = {2013}, author = {Sebé-Pedrós, A and Irimia, M and Del Campo, J and Parra-Acero, H and Russ, C and Nusbaum, C and Blencowe, BJ and Ruiz-Trillo, I}, title = {Regulated aggregative multicellularity in a close unicellular relative of metazoa.}, journal = {eLife}, volume = {2}, number = {}, pages = {e01287}, pmid = {24368732}, issn = {2050-084X}, support = {206883/ERC_/European Research Council/International ; MOP-67011/CAPMC/CIHR/Canada ; }, mesh = {Adaptation, Psychological ; Alternative Splicing ; Amoeba/classification/genetics/growth & development/*physiology ; Cell Cycle ; *Cell Division/genetics ; *Evolution, Molecular ; Gene Expression Regulation ; Phylogeny ; Time Factors ; }, abstract = {The evolution of metazoans from their unicellular ancestors was one of the most important events in the history of life. However, the cellular and genetic changes that ultimately led to the evolution of multicellularity are not known. In this study, we describe an aggregative multicellular stage in the protist Capsaspora owczarzaki, a close unicellular relative of metazoans. Remarkably, transition to the aggregative stage is associated with significant upregulation of orthologs of genes known to establish multicellularity and tissue architecture in metazoans. We further observe transitions in regulated alternative splicing during the C. owczarzaki life cycle, including the deployment of an exon network associated with signaling, a feature of splicing regulation so far only observed in metazoans. Our results reveal the existence of a highly regulated aggregative stage in C. owczarzaki and further suggest that features of aggregative behavior in an ancestral protist may had been co-opted to develop some multicellular properties currently seen in metazoans. DOI: http://dx.doi.org/10.7554/eLife.01287.001.}, } @article {pmid24367511, year = {2013}, author = {Libby, E and Rainey, PB}, title = {Eco-evolutionary feedback and the tuning of proto-developmental life cycles.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e82274}, pmid = {24367511}, issn = {1932-6203}, mesh = {Animals ; *Life Cycle Stages ; *Models, Theoretical ; }, abstract = {Multicellular organisms depend on developmental programs to coordinate growth and differentiation from single cells, but the origins of development are unclear. A possible starting point is stochastic phenotypic variation generated by molecular noise. Given appropriate environmental conditions, noise-driven differentiation could conceivably evolve so as to come under regulatory control; however, abiotic conditions are likely to be restrictive. Drawing from an experimental system, we present a model in which environmental fluctuations are coupled to population growth. We show that this coupling generates stable selection for a single optimal strategy that is largely insensitive to environmental conditions, including the number of competitors, carrying capacity of the environment, difference in growth rates among phenotypic variants, and population density. We argue that this optimal strategy establishes stabilizing conditions likely to improve the quality and reliability of information experienced by evolving organisms, thus increasing opportunity for the evolutionary emergence of developmental programs.}, } @article {pmid24363320, year = {2014}, author = {Niklas, KJ}, title = {The evolutionary-developmental origins of multicellularity.}, journal = {American journal of botany}, volume = {101}, number = {1}, pages = {6-25}, doi = {10.3732/ajb.1300314}, pmid = {24363320}, issn = {1537-2197}, mesh = {*Biological Evolution ; Cell Adhesion ; Eukaryotic Cells/*cytology ; *Growth and Development ; Phylogeny ; }, abstract = {Multicellularity has evolved at least once in every major eukaryotic clade (in all ploidy levels) and numerous times among the prokaryotes. According to a standard multilevel selection (MLS) model, in each case, the evolution of multicellularity required the acquisition of cell-cell adhesion, communication, cooperation, and specialization attended by a compulsory alignment-of-fitness phase and an export-of-fitness phase to eliminate cell-cell conflict and to establish a reproductively integrated phenotype. These achievements are reviewed in terms of generalized evolutionary developmental motifs (or "modules") whose overall logic constructs were mobilized and executed differently in bacteria, plants, fungi, and animals. When mapped onto a matrix of theoretically possible body plan morphologies (i.e., a morphospace), these motifs and the MLS model identify a "unicellular ⇒ colonial ⇒ multicellular" transformation series of body plans that mirrors trends observed in the majority of algae (i.e., a polyphyletic collection of photoautotrophic eukaryotes) and in the land plants, fungi, and animals. However, an alternative, more direct route to multicellularity theoretically exists, which may account for some aspects of fungal and algal evolution, i.e., a "siphonous ⇒ multicellular" transformation series. This review of multicellularity attempts to show that natural selection typically acts on functional traits rather than on the mechanisms that generate them ("Many roads lead to Rome.") and that genome sequence homologies do not invariably translate into morphological homologies ("Rome isn't what it used to be.").}, } @article {pmid24361965, year = {2014}, author = {Meersseman, C and Léjard, V and Rebours, E and Boussaha, M and Maftah, A and Petit, D and Rocha, D}, title = {Bovine TWINKLE and mitochondrial ribosomal protein L43 genes are regulated by an evolutionary conserved bidirectional promoter.}, journal = {Gene}, volume = {537}, number = {1}, pages = {154-163}, doi = {10.1016/j.gene.2013.11.088}, pmid = {24361965}, issn = {1879-0038}, mesh = {5' Flanking Region ; Animals ; Base Sequence ; Binding Sites ; Cattle ; Cell Line ; DNA Helicases/*genetics ; DNA, Intergenic ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Mitochondrial Proteins/*genetics ; Molecular Sequence Data ; *Promoter Regions, Genetic ; Ribosomal Proteins/*genetics ; Transcription Factors/genetics/metabolism ; Vertebrates/genetics ; }, abstract = {TWINKLE is a mitochondrial DNA helicase playing an important role in mitochondrial DNA replication. In human, mutations in this gene cause progressive external ophtalmoplegia and mitochondrial DNA depletion syndrome-7. TWINKLE is well conserved among multicellular eukaryotes and is believed to be a key regulator of mitochondrial DNA copy number in mammals. Despite its involvement in several diseases and its important function in mitochondrial DNA metabolism, nothing is known about the regulation of the expression of TWINKLE. We have analysed the 5'-flanking genomic region of the bovine TWINKLE gene and found it was localised adjacent to the MRPL43 gene in a head-to-head orientation, suggesting that both genes are regulated by a shared bidirectional promoter. The bovine 75-bp long intergenic region shows substantial homology across different species and contains several conserved putative transcription factor binding sites. A TATA box, however, was lacking. Using a dual fluorescent reporter system and transient transfection assays, we have analysed the bovine intergenic region between TWINKLE and MRPL43. This small genomic fragment showed a bidirectional promoter activity. As the TWINKLE/MRPL43 bidirectional promoter tested was highly conserved, it is likely that the results we obtained here in cattle may be extended to the other species.}, } @article {pmid24361581, year = {2014}, author = {Bull, L}, title = {Evolving Boolean regulatory networks with epigenetic control.}, journal = {Bio Systems}, volume = {116}, number = {}, pages = {36-42}, doi = {10.1016/j.biosystems.2013.12.004}, pmid = {24361581}, issn = {1872-8324}, mesh = {DNA Methylation ; *Epigenesis, Genetic ; *Gene Regulatory Networks ; Models, Theoretical ; Transcription, Genetic ; }, abstract = {The significant role of epigenetic mechanisms within natural systems has become increasingly clear. This paper uses a recently presented abstract, tunable Boolean genetic regulatory network model to explore aspects of epigenetics. It is shown how dynamically controlling transcription via a DNA methylation-inspired mechanism can be selected for by simulated evolution under various single and multicellular scenarios. Further, it is shown that the effects of such control can be inherited without detriment to fitness.}, } @article {pmid24361339, year = {2014}, author = {Bersini, S and Jeon, JS and Moretti, M and Kamm, RD}, title = {In vitro models of the metastatic cascade: from local invasion to extravasation.}, journal = {Drug discovery today}, volume = {19}, number = {6}, pages = {735-742}, pmid = {24361339}, issn = {1878-5832}, support = {R21 CA140096/CA/NCI NIH HHS/United States ; R33 CA174550/CA/NCI NIH HHS/United States ; R33 CA174550-01/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Humans ; Microfluidic Analytical Techniques/*methods ; Neoplasm Invasiveness/*pathology ; Neoplasms/blood/diagnosis ; Neoplastic Cells, Circulating/*pathology ; Signal Transduction/physiology ; }, abstract = {A crucial event in the metastatic cascade is the extravasation of circulating cancer cells from blood capillaries to the surrounding tissues. The past 5 years have been characterized by a significant evolution in the development of in vitro extravasation models, which moved from traditional transmigration chambers to more sophisticated microfluidic devices, enabling the study of complex cell-cell and cell-matrix interactions in multicellular, controlled environments. These advanced assays could be applied to screen easily and rapidly a broad spectrum of molecules inhibiting cancer cell endothelial adhesion and extravasation, thus contributing to the design of more focused in vivo tests.}, } @article {pmid24360576, year = {2014}, author = {Charoen, KM and Fallica, B and Colson, YL and Zaman, MH and Grinstaff, MW}, title = {Embedded multicellular spheroids as a biomimetic 3D cancer model for evaluating drug and drug-device combinations.}, journal = {Biomaterials}, volume = {35}, number = {7}, pages = {2264-2271}, pmid = {24360576}, issn = {1878-5905}, support = {R01 CA149561/CA/NCI NIH HHS/United States ; T32 EB006359/EB/NIBIB NIH HHS/United States ; T32EB006359/EB/NIBIB NIH HHS/United States ; T32 GM008541/GM/NIGMS NIH HHS/United States ; R25 CA153955/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents/*therapeutic use ; *Biomimetics ; Cell Line, Tumor ; Drug Evaluation, Preclinical ; *Equipment and Supplies ; Humans ; *Imaging, Three-Dimensional ; *Microspheres ; Neoplasms/drug therapy/*pathology/therapy ; }, abstract = {Multicellular aggregates of cells, termed spheroids, are of interest for studying tumor behavior and for evaluating the response of pharmacologically active agents. Spheroids more faithfully reproduce the tumor macrostructure found in vivo compared to classical 2D monolayers. We present a method for embedding spheroids within collagen gels followed by quantitative and qualitative whole spheroid and single cell analyses enabling characterization over the length scales from molecular to macroscopic. Spheroid producing and embedding capabilities are demonstrated for U2OS and MDA-MB-231 cell lines, of osteosarcoma and breast adenocarcinoma origin, respectively. Finally, using the MDA-MB-231 tumor model, the chemotherapeutic response between paclitaxel delivery as a bolus dose, as practiced in the clinic, is compared to delivery within an expansile nanoparticle. The expansile nanoparticle delivery route provides a superior outcome and the results mirror those observed in a murine xenograft model. These findings highlight the synergistic beneficial results that may arise from the use of a drug delivery system, and the need to evaluate both drug candidates and delivery systems in the research and preclinical screening phases of a new cancer therapy development program.}, } @article {pmid24353202, year = {2014}, author = {Woods, HA}, title = {Mosaic physiology from developmental noise: within-organism physiological diversity as an alternative to phenotypic plasticity and phenotypic flexibility.}, journal = {The Journal of experimental biology}, volume = {217}, number = {Pt 1}, pages = {35-45}, doi = {10.1242/jeb.089698}, pmid = {24353202}, issn = {1477-9145}, mesh = {Acclimatization/*physiology ; Allostasis/*physiology ; Animals ; Biodiversity ; Biological Evolution ; Environment ; Homeostasis/*physiology ; Stochastic Processes ; *Stress, Physiological ; }, abstract = {A key problem in organismal biology is to explain the origins of functional diversity. In the context of organismal biology, functional diversity describes the set of phenotypes, across scales of biological organization and through time, that a single genotype, or genome, or organism, can produce. Functional diversity encompasses many phenomena: differences in cell types within organisms; physiological and morphological differences among tissues and organs; differences in performance; morphological shifts in external phenotype; and changes in behavior. How can single genomes produce so many different phenotypes? Modern biology proposes two general mechanisms. The first is developmental programs, by which single cells and their single genomes diversify, via relatively deterministic processes, into the sets of cell types, tissues and organs that we see in most multicellular organisms. The second general mechanism is phenotypic modification stemming from interactions between organisms and their environments - modifications known either as phenotypic plasticity or as phenotypic flexibility, depending on the time scale of the response and the degree of reversibility. These two diversity-generating mechanisms are related because phenotypic modifications may sometimes arise as a consequence of environments influencing developmental programs. Here, I propose that functional diversity also arises via a third fundamental mechanism: stochastic developmental events giving rise to mosaics of physiological diversity within individual organisms. In biological systems, stochasticity stems from the inherently random actions of small numbers of molecules interacting with one another. Although stochastic effects occur in many biological contexts, available evidence suggests that they can be especially important in gene networks, specifically as a consequence of low transcript numbers in individual cells. I briefly review known mechanisms by which organisms control such stochasticity, and how they may use it to create adaptive functional diversity. I then fold this idea into modern thinking on phenotypic plasticity and flexibility, proposing that multicellular organisms exhibit 'mosaic physiology'. Mosaic physiology refers to sets of diversified phenotypes, within individual organisms, that carry out related functions at the same time, but that are distributed in space. Mosaic physiology arises from stochasticity-driven differentiation of cells, early during cell diversification, which is then amplified by cell division and growth into macroscopic phenotypic modules (cells, tissues, organs) making up the physiological systems of later life stages. Mosaic physiology provides a set of standing, diversified phenotypes, within single organisms, that raise the likelihood of the organism coping well with novel environmental challenges. These diversified phenotypes can be distinct, akin to polyphenisms at the organismal level; or they can be continuously distributed, creating a kind of standing, simultaneously expressed reaction norm of physiological capacities.}, } @article {pmid24349132, year = {2013}, author = {Kuwayama, H and Miyanaga, Y and Urushihara, H and Ueda, M}, title = {A RabGAP regulates life-cycle duration via trimeric G-protein cascades in Dictyostelium discoideum.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e81811}, pmid = {24349132}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans ; Cell Proliferation ; Dictyostelium/*genetics/metabolism ; GTPase-Activating Proteins/*genetics/metabolism ; Gene Deletion ; Gene Expression Regulation ; Genetic Complementation Test ; Humans ; Life Cycle Stages/*genetics ; Microtubule-Associated Proteins/*genetics/metabolism ; Molecular Sequence Data ; Protein Binding ; Protein Multimerization ; Protozoan Proteins/*genetics/metabolism ; Sequence Alignment ; Signal Transduction ; Two-Hybrid System Techniques ; }, abstract = {BACKGROUND: The life-cycle of cellular slime molds comprises chronobiologically regulated processes. During the growth phase, the amoeboid cells proliferate at a definite rate. Upon starvation, they synthesize cAMP as both first and second messengers in signalling pathways and form aggregates, migrating slugs, and fruiting bodies, consisting of spores and stalk cells, within 24 h. In Dictyostelium discoideum, because most growth-specific events cease during development, proliferative and heterochronic mutations are not considered to be interrelated and no genetic factor governing the entire life-cycle duration has ever been identified.

Using yeast 2-hybrid library screening, we isolated a Dictyostelium discoideum RabGAP, Dd Rbg-3, as a candidate molecule by which the Dictyostelium Gα2 subunit directs its effects. Rab GTPase-activating protein, RabGAP, acts as a negative regulator of Rab small GTPases, which orchestrate the intracellular membrane trafficking involved in cell proliferation. Deletion mutants of Dd rbg-3 exhibited an increased growth rate and a shortened developmental period, while an overexpression mutant demonstrated the opposite effects. We also show that Dd Rbg-3 interacts with 2 Gα subunits in an activity-dependent manner in vitro. Furthermore, both human and Caenorhabditis elegans rbg-3 homologs complemented the Dd rbg-3-deletion phenotype in D. discoideum, indicating that similar pathways may be generally conserved in multicellular organisms.

CONCLUSIONS/SIGNIFICANCE: Our findings suggest that Dd Rbg-3 acts as a key element regulating the duration of D. discoideum life-span potentially via trimeric G-protein cascades.}, } @article {pmid24349103, year = {2013}, author = {Arakaki, Y and Kawai-Toyooka, H and Hamamura, Y and Higashiyama, T and Noga, A and Hirono, M and Olson, BJ and Nozaki, H}, title = {The simplest integrated multicellular organism unveiled.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e81641}, pmid = {24349103}, issn = {1932-6203}, mesh = {*Biological Evolution ; Chlorophyta/classification/physiology/*ultrastructure ; Cytoplasm/physiology/ultrastructure ; Extracellular Matrix/physiology/ultrastructure ; Flagella/physiology/ultrastructure ; *Phylogeny ; Protoplasts/physiology/ultrastructure ; Species Specificity ; }, abstract = {Volvocine green algae represent the "evolutionary time machine" model lineage for studying multicellularity, because they encompass the whole range of evolutionary transition of multicellularity from unicellular Chlamydomonas to >500-celled Volvox. Multicellular volvocalean species including Gonium pectorale and Volvox carteri generally have several common morphological features to survive as integrated multicellular organisms such as "rotational asymmetry of cells" so that the cells become components of the individual and "cytoplasmic bridges between protoplasts in developing embryos" to maintain the species-specific form of the multicellular individual before secretion of new extracellular matrix (ECM). However, these morphological features have not been studied in the four-celled colonial volvocine species Tetrabaena socialis that is positioned in the most basal lineage within the colonial or multicellular volvocine greens. Here we established synchronous cultures of T. socialis and carried out immunofluorescence microscopic and ultrastructural observations to elucidate these two morphological attributes. Based on immunofluorescence microscopy, four cells of the mature T. socialis colony were identical in morphology but had rotational asymmetry in arrangement of microtubular rootlets and separation of basal bodies like G. pectorale and V. carteri. Ultrastructural observations clearly confirmed the presence of cytoplasmic bridges between protoplasts in developing embryos of T. socialis even after the formation of new flagella in each daughter protoplast within the parental ECM. Therefore, these two morphological attributes might have evolved in the common four-celled ancestor of the colonial volvocine algae and contributed to the further increase in cell number and complexity of the multicellular individuals of this model lineage. T. socialis is one of the simplest integrated multicellular organisms in which four identical cells constitute the individual.}, } @article {pmid24339376, year = {2014}, author = {Kramer, S}, title = {RNA in development: how ribonucleoprotein granules regulate the life cycles of pathogenic protozoa.}, journal = {Wiley interdisciplinary reviews. RNA}, volume = {5}, number = {2}, pages = {263-284}, doi = {10.1002/wrna.1207}, pmid = {24339376}, issn = {1757-7012}, mesh = {Apicomplexa/genetics/*metabolism ; Cytoplasmic Granules/genetics/metabolism ; Gene Expression Regulation/*physiology ; Oocytes/metabolism ; Protozoan Proteins/genetics/*metabolism ; RNA, Protozoan/genetics/*metabolism ; Ribonucleoproteins/genetics/*metabolism ; Trypanosoma/genetics/*metabolism ; }, abstract = {Ribonucleoprotein (RNP) granules are important posttranscriptional regulators of messenger RNA (mRNA) fate. Several types of RNP granules specifically regulate gene expression during development of multicellular organisms and are commonly referred to as germ granules. The function of germ granules is not entirely understood and probably diverse, but it is generally agreed that one main function is posttranscriptional regulation of gene expression during early development, when transcription is silent. One example is the translational repression of maternally derived mRNAs in oocytes. Here, I hope to show that the need for regulation of gene expression by RNP granules is not restricted to animal development, but plays an equally important role during the development of pathogenic protozoa. Apicomplexa and Trypanosomatidae have complex life cycles with frequent host changes. The need to quickly adapt gene expression to a new environment as well as the ability to suppress translation to survive latencies is critical for successful completion of life cycles. Posttranscriptional gene regulation is not necessarily simpler in protozoa. Apicomplexa surprise with the presence of micro RNA (miRNAs) and upstream open reading frames (µORFs). Trypanosomes have an unusually large repertoire of different RNP granule types. A better understanding of RNP granules in protozoa may help to gain insight into the evolutionary origin of RNP granules: Trypanosomes for example have two types of granules with interesting similarities to animal germ granules.}, } @article {pmid24336809, year = {2014}, author = {Ofer, D and Linial, M}, title = {NeuroPID: a predictor for identifying neuropeptide precursors from metazoan proteomes.}, journal = {Bioinformatics (Oxford, England)}, volume = {30}, number = {7}, pages = {931-940}, doi = {10.1093/bioinformatics/btt725}, pmid = {24336809}, issn = {1367-4811}, mesh = {Amino Acid Sequence ; Animals ; *Artificial Intelligence ; Databases, Genetic ; Insecta ; Molecular Sequence Data ; Neuropeptides/*analysis/chemistry ; Protein Precursors/analysis ; Proteome/*analysis/chemistry ; Sequence Alignment ; Sequence Homology, Amino Acid ; *Software ; Support Vector Machine ; }, abstract = {MOTIVATION: The evolution of multicellular organisms is associated with increasing variability of molecules governing behavioral and physiological states. This is often achieved by neuropeptides (NPs) that are produced in neurons from a longer protein, named neuropeptide precursor (NPP). The maturation of NPs occurs through a sequence of proteolytic cleavages. The difficulty in identifying NPPs is a consequence of their diversity and the lack of applicable sequence similarity among the short functionally related NPs.

RESULTS: Herein, we describe Neuropeptide Precursor Identifier (NeuroPID), a machine learning scheme that predicts metazoan NPPs. NeuroPID was trained on hundreds of identified NPPs from the UniProtKB database. Some 600 features were extracted from the primary sequences and processed using support vector machines (SVM) and ensemble decision tree classifiers. These features combined biophysical, chemical and informational-statistical properties of NPs and NPPs. Other features were guided by the defining characteristics of the dibasic cleavage sites motif. NeuroPID reached 89-94% accuracy and 90-93% precision in cross-validation blind tests against known NPPs (with an emphasis on Chordata and Arthropoda). NeuroPID also identified NPP-like proteins from extensively studied model organisms as well as from poorly annotated proteomes. We then focused on the most significant sets of features that contribute to the success of the classifiers. We propose that NPPs are attractive targets for investigating and modulating behavior, metabolism and homeostasis and that a rich repertoire of NPs remains to be identified.

AVAILABILITY: NeuroPID source code is freely available at http://www.protonet.cs.huji.ac.il/neuropid}, } @article {pmid24335705, year = {2014}, author = {Kempes, CP and Okegbe, C and Mears-Clarke, Z and Follows, MJ and Dietrich, LE}, title = {Morphological optimization for access to dual oxidants in biofilms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {1}, pages = {208-213}, pmid = {24335705}, issn = {1091-6490}, support = {R01 AI103369/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; 1 R01 AI103369-01A1/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Physiological Phenomena ; *Biofilms ; Calibration ; Electrodes ; Kinetics ; Models, Theoretical ; Mutation ; Oxidants/*chemistry ; Oxidation-Reduction ; Oxygen/*chemistry ; Phenazines/chemistry ; Pseudomonas aeruginosa/*metabolism ; Signal Transduction ; Temperature ; }, abstract = {A major theme driving research in biology is the relationship between form and function. In particular, a longstanding goal has been to understand how the evolution of multicellularity conferred fitness advantages. Here we show that biofilms of the bacterium Pseudomonas aeruginosa produce structures that maximize cellular reproduction. Specifically, we develop a mathematical model of resource availability and metabolic response within colony features. This analysis accurately predicts the measured distribution of two types of electron acceptors: oxygen, which is available from the atmosphere, and phenazines, redox-active antibiotics produced by the bacterium. Using this model, we demonstrate that the geometry of colony structures is optimal with respect to growth efficiency. Because our model is based on resource dynamics, we also can anticipate shifts in feature geometry based on changes to the availability of electron acceptors, including variations in the external availability of oxygen and genetic manipulation that renders the cells incapable of phenazine production.}, } @article {pmid24333018, year = {2014}, author = {Dunin-Horkawicz, S and Kopec, KO and Lupas, AN}, title = {Prokaryotic ancestry of eukaryotic protein networks mediating innate immunity and apoptosis.}, journal = {Journal of molecular biology}, volume = {426}, number = {7}, pages = {1568-1582}, doi = {10.1016/j.jmb.2013.11.030}, pmid = {24333018}, issn = {1089-8638}, mesh = {Amino Acid Sequence ; Apoptosis/genetics/*physiology ; Computational Biology ; Eukaryotic Cells/cytology/metabolism ; Immunity, Innate/genetics/*physiology ; Molecular Sequence Data ; Prokaryotic Cells/cytology/metabolism ; Proteins/*chemistry/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {Protein domains characteristic of eukaryotic innate immunity and apoptosis have many prokaryotic counterparts of unknown function. By reconstructing interactomes computationally, we found that bacterial proteins containing these domains are part of a network that also includes other domains not hitherto associated with immunity. This network is connected to the network of prokaryotic signal transduction proteins, such as histidine kinases and chemoreceptors. The network varies considerably in domain composition and degree of paralogy, even between strains of the same species, and its repetitive domains are often amplified recently, with individual repeats sharing up to 100% sequence identity. Both phenomena are evidence of considerable evolutionary pressure and thus compatible with a role in the "arms race" between host and pathogen. In order to investigate the relationship of this network to its eukaryotic counterparts, we performed a cluster analysis of organisms based on a census of its constituent domains across all fully sequenced genomes. We obtained a large central cluster of mainly unicellular organisms, from which multicellular organisms radiate out in two main directions. One is taken by multicellular bacteria, primarily cyanobacteria and actinomycetes, and plants form an extension of this direction, connected via the basal, unicellular cyanobacteria. The second main direction is taken by animals and fungi, which form separate branches with a common root in the α-proteobacteria of the central cluster. This analysis supports the notion that the innate immunity networks of eukaryotes originated from their endosymbionts and that increases in the complexity of these networks accompanied the emergence of multicellularity.}, } @article {pmid24313842, year = {2014}, author = {Urano, D and Jones, AM}, title = {Heterotrimeric G protein-coupled signaling in plants.}, journal = {Annual review of plant biology}, volume = {65}, number = {}, pages = {365-384}, pmid = {24313842}, issn = {1545-2123}, support = {R01 GM065989/GM/NIGMS NIH HHS/United States ; R01GM065989/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/metabolism ; Heterotrimeric GTP-Binding Proteins/*metabolism ; Models, Molecular ; Plant Proteins/*metabolism ; Plants/*metabolism ; Protein Structure, Secondary ; Signal Transduction ; }, abstract = {Investigators studying G protein-coupled signaling--often called the best-understood pathway in the world owing to intense research in medical fields--have adopted plants as a new model to explore the plasticity and evolution of G signaling. Much research on plant G signaling has not disappointed. Although plant cells have most of the core elements found in animal G signaling, differences in network architecture and intrinsic properties of plant G protein elements make G signaling in plant cells distinct from the animal paradigm. In contrast to animal G proteins, plant G proteins are self-activating, and therefore regulation of G activation in plants occurs at the deactivation step. The self-activating property also means that plant G proteins do not need and therefore do not have typical animal G protein-coupled receptors. Targets of activated plant G proteins, also known as effectors, are unlike effectors in animal cells. The simpler repertoire of G signal elements in Arabidopsis makes G signaling easier to manipulate in a multicellular context.}, } @article {pmid24307687, year = {2014}, author = {Suga, H and Torruella, G and Burger, G and Brown, MW and Ruiz-Trillo, I}, title = {Earliest Holozoan expansion of phosphotyrosine signaling.}, journal = {Molecular biology and evolution}, volume = {31}, number = {3}, pages = {517-528}, pmid = {24307687}, issn = {1537-1719}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Animals ; Choanoflagellata/*enzymology ; Evolution, Molecular ; Mesomycetozoea/enzymology ; Models, Molecular ; Phosphotyrosine/*metabolism ; Phylogeny ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases/chemistry ; *Signal Transduction ; }, abstract = {Phosphotyrosine (pTyr) signaling is involved in development and maintenance of metazoans' multicellular body through cell-to-cell communication. Tyrosine kinases (TKs), tyrosine phosphatases, and other proteins relaying the signal compose the cascade. Domain architectures of the pTyr signaling proteins are diverse in metazoans, reflecting their complex intercellular communication. Previous studies had shown that the metazoan-type TKs, as well as other pTyr signaling proteins, were already diversified in the common ancestor of metazoans, choanoflagellates, and filastereans (which are together included in the clade Holozoa) whereas they are absent in fungi and other nonholozoan lineages. However, the earliest-branching holozoans Ichthyosporea and Corallochytrea, as well as the two fungi-related amoebae Fonticula and Nuclearia, have not been studied. Here, we analyze the complete genome sequences of two ichthyosporeans and Fonticula, and RNAseq data of three additional ichthyosporeans, one corallochytrean, and Nuclearia. Both the ichthyosporean and corallochytrean genomes encode a large variety of receptor TKs (RTKs) and cytoplasmic TKs (CTKs), as well as other pTyr signaling components showing highly complex domain architectures. However, Nuclearia and Fonticula have no TK, and show much less diversity in other pTyr signaling components. The CTK repertoires of both Ichthyosporea and Corallochytrea are similar to those of Metazoa, Choanoflagellida, and Filasterea, but the RTK sets are totally different from each other. The complex pTyr signaling equipped with positive/negative feedback mechanism likely emerged already at an early stage of holozoan evolution, yet keeping a high evolutionary plasticity in extracellular signal reception until the co-option of the system for cell-to-cell communication in metazoans.}, } @article {pmid24307295, year = {2013}, author = {Tischer, S and Reineck, M and Söding, J and Münder, S and Böttger, A}, title = {Eph receptors and ephrin class B ligands are expressed at tissue boundaries in Hydra vulgaris.}, journal = {The International journal of developmental biology}, volume = {57}, number = {9-10}, pages = {759-765}, doi = {10.1387/ijdb.130158ab}, pmid = {24307295}, issn = {1696-3547}, mesh = {Amino Acid Sequence ; Animals ; Cell Adhesion/*physiology ; Ephrins/*biosynthesis ; Epithelial Cells/metabolism ; Hydra ; Phylogeny ; Protein Structure, Tertiary ; Receptors, Eph Family/*biosynthesis ; Sequence Alignment ; Signal Transduction ; }, abstract = {Eph receptors and ephrins are important players in axon guidance, cell sorting and boundary formation. Both the receptors and the ligands are integrated transmembrane proteins and signalling is bidirectional. The prevalent outcome of signal transduction is repulsion of adjacent cells or cell populations. Eph/ephrins have been identified in all multicellular animals from human to sponge, their functions however appear to have been altered during evolution. Here we have identified four Eph receptors and three class B ligands in the cnidarian Hydra vulgaris, indicating that those are the evolutionary older ones. In situ hybridisation experiments revealed a striking complementarity of expression of receptors and ligands in tentacles and in developing buds. This suggests that the original function of ephrin signalling may have been in epithelial cell adhesion and the formation of tissue boundaries.}, } @article {pmid24301834, year = {2014}, author = {Urbisz, AZ and Lai, YT and Swiątek, P}, title = {Barbronia weberi (Clitellata, Hirudinida, Salifidae) has ovary cords of the Erpobdella type.}, journal = {Journal of morphology}, volume = {275}, number = {5}, pages = {479-488}, doi = {10.1002/jmor.20229}, pmid = {24301834}, issn = {1097-4687}, mesh = {Animals ; Female ; Leeches/classification/physiology/*ultrastructure ; Oocytes/cytology/physiology/ultrastructure ; Ovary/anatomy & histology/physiology ; Phylogeny ; }, abstract = {The organization of the ovaries in representative of the Salifidae (Hirudinida, Erpobdelliformes) was studied at the ultrastructural level for the first time. Like in other leeches, the ovaries of Barbronia weberi are composed of an outer envelope (i.e., an ovisac made up of two coelomic epithelia, muscle cells, and connective tissue) and several internal units, which are broadly similar to the ovary cords found in representatives of the Erpobdellidae. There are usually 6-8 ovary cords that are twisted or cambered with a narrow apical part and a broader, irregularly shaped distal end in each ovisac of B. weberi. Each ovary cord is built from somatic and germ-line cells and the latter tend to form multicellular cysts that are equipped with a central cytoplasmic core (cytophore). There are two morphologically different subpopulations of germ-line cells: oocytes and more numerous nurse cells. Growing oocytes form protuberances on the ovary cord surface and eventually detach from the cord and float freely in the ovisac lumen, whereas the other components of germ-line cysts (i.e., nurse cells and cytophore) degenerate. It should be pointed out that there is a prominent gradient of germ-cell development along the long axis of the cord. The somatic cells form the ovary cord envelope (the so-called spongiosa cells) and also penetrate the spaces between germ-line cells. Both kinds of the somatic cells, that is, those forming the cord envelope and the somatic cells that are associated with oocytes (follicular cells) have a well-developed system of intercellular channels. Additionally, one prominent somatic cell, the apical cell, was found at the apical tip of each ovary cord. Because the aforementioned features of ovary cords found in B. weberi are very similar (with a few minor exceptions) to the ovary cords that have been described in Erpobdella octoculata and E. johanssoni, we propose the term "ovary cords of the Erpobdella type" for them. Our results support a close phylogenetic relationship between Salifidae and Erpobdellidae.}, } @article {pmid24298060, year = {2014}, author = {Covo, S and Puccia, CM and Argueso, JL and Gordenin, DA and Resnick, MA}, title = {The sister chromatid cohesion pathway suppresses multiple chromosome gain and chromosome amplification.}, journal = {Genetics}, volume = {196}, number = {2}, pages = {373-384}, pmid = {24298060}, issn = {1943-2631}, support = {Z01 ES065073//Intramural NIH HHS/United States ; 1Z01ES065073/ES/NIEHS NIH HHS/United States ; }, mesh = {Aneuploidy ; Cell Cycle Proteins/deficiency/genetics ; Chromatids/*genetics/metabolism ; Chromosomal Proteins, Non-Histone/deficiency/genetics ; *Chromosome Aberrations ; Chromosomes, Fungal/*genetics/metabolism ; Copper Sulfate/toxicity ; DNA Copy Number Variations ; DNA Damage ; Diploidy ; Drug Resistance, Fungal/genetics ; Gene Amplification ; Mutation ; Saccharomyces cerevisiae/drug effects/*genetics/metabolism ; }, abstract = {Gain or loss of chromosomes resulting in aneuploidy can be important factors in cancer and adaptive evolution. Although chromosome gain is a frequent event in eukaryotes, there is limited information on its genetic control. Here we measured the rates of chromosome gain in wild-type yeast and sister chromatid cohesion (SCC) compromised strains. SCC tethers the newly replicated chromatids until anaphase via the cohesin complex. Chromosome gain was measured by selecting and characterizing copper-resistant colonies that emerged due to increased copies of the metallothionein gene CUP1. Although all defective SCC diploid strains exhibited increased rates of chromosome gain, there were 15-fold differences between them. Of all mutants examined, a hypomorphic mutation at the cohesin complex caused the highest rate of chromosome gain while disruption of WPL1, an important regulator of SCC and chromosome condensation, resulted in the smallest increase in chromosome gain. In addition to defects in SCC, yeast cell type contributed significantly to chromosome gain, with the greatest rates observed for homozygous mating-type diploids, followed by heterozygous mating type, and smallest in haploids. In fact, wpl1-deficient haploids did not show any difference in chromosome gain rates compared to wild-type haploids. Genomic analysis of copper-resistant colonies revealed that the "driver" chromosome for which selection was applied could be amplified to over five copies per diploid cell. In addition, an increase in the expected driver chromosome was often accompanied by a gain of a small number of other chromosomes. We suggest that while chromosome gain due to SCC malfunction can have negative effects through gene imbalance, it could also facilitate opportunities for adaptive changes. In multicellular organisms, both factors could lead to somatic diseases including cancer.}, } @article {pmid24296535, year = {2014}, author = {Fatica, A and Bozzoni, I}, title = {Long non-coding RNAs: new players in cell differentiation and development.}, journal = {Nature reviews. Genetics}, volume = {15}, number = {1}, pages = {7-21}, pmid = {24296535}, issn = {1471-0064}, support = {GGP11149/TI_/Telethon/Italy ; }, mesh = {Animals ; Cell Differentiation/*genetics/physiology ; Cytoplasm/genetics ; Dosage Compensation, Genetic/*genetics ; Gene Expression Regulation, Developmental/*genetics ; Genomic Imprinting/*genetics ; Mammals/*genetics/growth & development ; *Models, Genetic ; Models, Molecular ; Muscles/physiology ; Organogenesis/*genetics ; RNA, Long Noncoding/*genetics ; Species Specificity ; }, abstract = {Genomes of multicellular organisms are characterized by the pervasive expression of different types of non-coding RNAs (ncRNAs). Long ncRNAs (lncRNAs) belong to a novel heterogeneous class of ncRNAs that includes thousands of different species. lncRNAs have crucial roles in gene expression control during both developmental and differentiation processes, and the number of lncRNA species increases in genomes of developmentally complex organisms, which highlights the importance of RNA-based levels of control in the evolution of multicellular organisms. In this Review, we describe the function of lncRNAs in developmental processes, such as in dosage compensation, genomic imprinting, cell differentiation and organogenesis, with a particular emphasis on mammalian development.}, } @article {pmid24295300, year = {2013}, author = {Balklava, Z and Sztul, E}, title = {Studying membrane trafficking in the worm C. elegans by RNA interference.}, journal = {Methods in cell biology}, volume = {118}, number = {}, pages = {51-68}, doi = {10.1016/B978-0-12-417164-0.00004-5}, pmid = {24295300}, issn = {0091-679X}, mesh = {Animals ; Biological Transport ; Caenorhabditis elegans/cytology/genetics/*metabolism ; Caenorhabditis elegans Proteins/*genetics/metabolism ; Cell Membrane/metabolism ; Escherichia coli ; *Gene Knockdown Techniques ; Gene Transfer Techniques ; Green Fluorescent Proteins ; Membrane Transport Proteins/genetics/metabolism ; Microscopy, Fluorescence ; *RNA Interference ; }, abstract = {A powerful approach to gain understanding of molecular machinery responsible for membrane trafficking is through inactivation of gene function by RNA interference (RNAi). RNAi-mediated gene silencing occurs when a double-stranded RNA is introduced into cells and targets a complementary mRNA for degradation. The subsequent lack of mRNA prevents the synthesis of the corresponding protein and ultimately causes depletion of a particular gene product from the cell. The effects of such depletion can then by analyzed by functional, morphological, and biochemical assays. RNAi-mediated knockdowns of numerous gene products in cultured cells of mammalian and other species origins have provided significant new insight into traffic regulation and represent standard approaches in current cell biology. However, RNAi in the multicellular nematode Caenorhabditis elegans model allows RNAi studies within the context of a whole organism, and thus provides an unprecedented opportunity to explore effects of specific trafficking regulators within the context of distinct developmental stages and diverse cell types. In addition, various transgenic C. elegans strains have been developed that express marker proteins tagged with fluorescent proteins to facilitate the analysis of trafficking within the secretory and endocytic pathways. This chapter provides a detailed description of a basic RNAi approach that can be used to analyze the function of any gene of interest in secretory and endosomal trafficking in C. elegans.}, } @article {pmid24293008, year = {2013}, author = {McCormack, R and de Armas, L and Shiratsuchi, M and Podack, ER}, title = {Killing machines: three pore-forming proteins of the immune system.}, journal = {Immunologic research}, volume = {57}, number = {1-3}, pages = {268-278}, pmid = {24293008}, issn = {1559-0755}, support = {F31 AI106290/AI/NIAID NIH HHS/United States ; P01 CA109094/CA/NCI NIH HHS/United States ; R01 CA039201/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/immunology ; Complement Membrane Attack Complex ; Extracellular Space/immunology/microbiology/virology ; Humans ; Immunity/*physiology ; Intracellular Space/immunology/microbiology ; Neoplasms/metabolism ; Pore Forming Cytotoxic Proteins/*physiology ; Virus Diseases/immunology/metabolism ; }, abstract = {The evolution of early multicellular eukaryotes 400-500 million years ago required a defensive strategy against microbial invasion. Pore-forming proteins containing the membrane-attack-complex-perforin (MACPF) domain were selected as the most efficient means to destroy bacteria or virally infected cells. The mechanism of pore formation by the MACPF domain is distinctive in that pore formation is purely physical and unspecific. The MACPF domain polymerizes, refolds, and inserts itself into bilayer membranes or bacterial outer cell walls. The displacement of surface lipid/carbohydrate molecules by the polymerizing MACPF domain creates clusters of large, water-filled holes that destabilize the barrier function and provide access for additional anti-bacterial or anti-viral effectors to sensitive sites that complete the destruction of the invader via enzymatic or chemical attack. The highly efficient mechanism of anti-microbial defense by a combined physical and chemical strategy using pore-forming MACPF-proteins has been retargeted during evolution of vertebrates and mammals for three purposes: (1) to kill extracellular bacteria C9/polyC9 evolved in conjunction with complement, (2) to kill virus infected and cancer cells perforin-1/polyperforin-1 CTL evolved targeted by NK and CTL, and (3) to kill intracellular bacteria transmembrane perforin-2/putative polyperforin-2 evolved targeted by phagocytic and nonphagocytic cells. Our laboratory has been involved in the discovery and description of each of the three pore-formers that will be reviewed here.}, } @article {pmid25984323, year = {2013}, author = {Coletti, D and Teodori, L and Lin, Z and Beranudin, JF and Adamo, S}, title = {Restoration versus reconstruction: cellular mechanisms of skin, nerve and muscle regeneration compared.}, journal = {Regenerative medicine research}, volume = {1}, number = {1}, pages = {4}, pmid = {25984323}, issn = {2050-490X}, abstract = {In tissues characterized by a high turnover or following acute injury, regeneration replaces damaged cells and is involved in adaptation to external cues, leading to homeostasis of many tissues during adult life. An understanding of the mechanics underlying tissue regeneration is highly relevant to regenerative medicine-based interventions. In order to investigate the existence a leitmotif of tissue regeneration, we compared the cellular aspects of regeneration of skin, nerve and skeletal muscle, three organs characterized by different types of anatomical and functional organization. Epidermis is a stratified squamous epithelium that migrates from the edge of the wound on the underlying dermis to rebuild lost tissue. Peripheral neurons are elongated cells whose neurites are organized in bundles, within an endoneurium of connective tissue; they either die upon injury or undergo remodeling and axon regrowth. Skeletal muscle is characterized by elongated syncytial cells, i.e. muscle fibers, that can temporarily survive in broken pieces; satellite cells residing along the fibers form new fibers, which ultimately fuse with the old ones as well as with each other to restore the previous organization. Satellite cell asymmetrical division grants a reservoir of undifferentiated cells, while other stem cell populations of muscle and non-muscle origin participate in muscle renewal. Following damage, all the tissues analyzed here go through three phases: inflammation, regeneration and maturation. Another common feature is the occurrence of cellular de-differentiation and/or differentiation events, including gene transcription, which are typical of embryonic development. Nonetheless, various strategies are used by different tissues to replace their lost parts. The epidermis regenerates ex novo, whereas neurons restore their missing parts; muscle fibers use a mixed strategy, based on the regrowth of missing parts through reconstruction by means of newborn fibers. The choice of either strategy is influenced by the anatomical, physical and chemical features of the cells as well as by the extracellular matrix typical of a given tissue, which points to the existence of differential, evolutionary-based mechanisms for specific tissue regeneration. The shared, ordered sequence of steps that characterize the regeneration processes examined suggests it may be possible to model this extremely important phenomenon to reproduce multicellular organisms.}, } @article {pmid24287596, year = {2013}, author = {Boughalmi, M and Pagnier, I and Aherfi, S and Colson, P and Raoult, D and La Scola, B}, title = {First isolation of a giant virus from wild Hirudo medicinalis leech: Mimiviridae isolation in Hirudo medicinalis.}, journal = {Viruses}, volume = {5}, number = {12}, pages = {2920-2930}, pmid = {24287596}, issn = {1999-4915}, mesh = {Acanthamoeba/growth & development ; Animals ; Cluster Analysis ; DNA, Viral/chemistry/genetics ; France ; Hirudo medicinalis/*virology ; Microscopy, Electron ; Mimiviridae/classification/genetics/*isolation & purification ; Phylogeny ; Sequence Analysis, DNA ; Sequence Homology ; Tunisia ; }, abstract = {Giant viruses and amoebae are common in freshwater, where they can coexist with other living multicellular organisms. We screened leeches from the species Hirudo medicinalis for giant viruses. We analyzed five H. medicinalis obtained from Tunisia (3) and France (2). The leeches were decontaminated and then dissected to remove internal parts for co-culture with Acanthamoeba polyphaga. The genomes of isolated viruses were sequenced on a 454 Roche instrument, and a comparative genomics analysis was performed. One Mimivirus was isolated and the strain was named Hirudovirus. The genome assembly generated two scaffolds, which were 1,155,382 and 25,660 base pairs in length. Functional annotations were identified for 47% of the genes, which corresponds to 466 proteins. The presence of Mimividae in the same ecological niche as wild Hirudo may explain the presence of the mimivirus in the digestive tract of the leech, and several studies have already shown that viruses can persist in the digestive tracts of leeches fed contaminated blood. As leeches can be used medically and Mimiviruses have the potential to be an infectious agent in humans, patients treated with leeches should be surveyed to investigate a possible connection.}, } @article {pmid24277850, year = {2013}, author = {de Mendoza, A and Sebé-Pedrós, A and Šestak, MS and Matejcic, M and Torruella, G and Domazet-Loso, T and Ruiz-Trillo, I}, title = {Transcription factor evolution in eukaryotes and the assembly of the regulatory toolkit in multicellular lineages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {50}, pages = {E4858-66}, pmid = {24277850}, issn = {1091-6490}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Cell Differentiation/*genetics ; Computational Biology ; Embryonic Development/*genetics ; Eukaryota/*genetics ; *Evolution, Molecular ; Gene Expression Regulation, Developmental/*genetics ; Genomics/methods ; Statistics, Nonparametric ; Transcription Factors/*genetics ; }, abstract = {Transcription factors (TFs) are the main players in transcriptional regulation in eukaryotes. However, it remains unclear what role TFs played in the origin of all of the different eukaryotic multicellular lineages. In this paper, we explore how the origin of TF repertoires shaped eukaryotic evolution and, in particular, their role into the emergence of multicellular lineages. We traced the origin and expansion of all known TFs through the eukaryotic tree of life, using the broadest possible taxon sampling and an updated phylogenetic background. Our results show that the most complex multicellular lineages (i.e., those with embryonic development, Metazoa and Embryophyta) have the most complex TF repertoires, and that these repertoires were assembled in a stepwise manner. We also show that a significant part of the metazoan and embryophyte TF toolkits evolved earlier, in their respective unicellular ancestors. To gain insights into the role of TFs in the development of both embryophytes and metazoans, we analyzed TF expression patterns throughout their ontogeny. The expression patterns observed in both groups recapitulate those of the whole transcriptome, but reveal some important differences. Our comparative genomics and expression data reshape our view on how TFs contributed to eukaryotic evolution and reveal the importance of TFs to the origins of multicellularity and embryonic development.}, } @article {pmid24277716, year = {2014}, author = {Bessa, J and Luengo, M and Rivero-Gil, S and Ariza-Cosano, A and Maia, AH and Ruiz-Ruano, FJ and Caballero, P and Naranjo, S and Carvajal, JJ and Gómez-Skarmeta, JL}, title = {A mobile insulator system to detect and disrupt cis-regulatory landscapes in vertebrates.}, journal = {Genome research}, volume = {24}, number = {3}, pages = {487-495}, pmid = {24277716}, issn = {1549-5469}, mesh = {Animals ; Animals, Genetically Modified ; DNA Transposable Elements/*genetics ; *Enhancer Elements, Genetic ; Fluorescence ; Genes, Reporter/physiology ; Genome ; Humans ; *Insulator Elements ; Mice ; Mutagenesis, Insertional/*methods ; Vertebrates/*genetics ; Zebrafish/genetics ; }, abstract = {In multicellular organisms, cis-regulation controls gene expression in space and time. Despite the essential implication of cis-regulation in the development and evolution of organisms and in human diseases, our knowledge about regulatory sequences largely derives from analyzing their activity individually and outside their genomic context. Indeed, the contribution of these sequences to the expression of their target genes in their genomic context is still largely unknown. Here we present a novel genetic screen designed to visualize and interrupt gene regulatory landscapes in vertebrates. In this screen, based on the random insertion of an engineered Tol2 transposon carrying a strong insulator separating two fluorescent reporter genes, we isolated hundreds of zebrafish lines containing insertions that disrupt the cis-regulation of tissue-specific expressed genes. We therefore provide a new easy-to-handle tool that will help to disrupt and chart the regulatory activity spread through the vast noncoding regions of the vertebrate genome.}, } @article {pmid24277295, year = {2014}, author = {Leducq, JB}, title = {Ecological genomics of adaptation and speciation in fungi.}, journal = {Advances in experimental medicine and biology}, volume = {781}, number = {}, pages = {49-72}, doi = {10.1007/978-94-007-7347-9_4}, pmid = {24277295}, issn = {0065-2598}, mesh = {Adaptation, Biological/*physiology ; *Ecosystem ; *Evolution, Molecular ; Fungi/*physiology ; *Gene-Environment Interaction ; Genome, Fungal/*physiology ; Humans ; *Metagenomics ; Quantitative Trait Loci/physiology ; }, abstract = {Fungi play a central role in both ecosystems and human societies. This is in part because they have adopted a large diversity of life history traits to conquer a wide variety of ecological niches. Here, I review recent fungal genomics studies that explored the molecular origins and the adaptive significance of this diversity. First, macro-ecological genomics studies revealed that fungal genomes were highly remodelled during their evolution. This remodelling, in terms of genome organization and size, occurred through the proliferation of non-coding elements, gene compaction, gene loss and the expansion of large families of adaptive genes. These features vary greatly among fungal clades, and are correlated with different life history traits such as multicellularity, pathogenicity, symbiosis, and sexual reproduction. Second, micro-ecological genomics studies, based on population genomics, experimental evolution and quantitative trait loci approaches, have allowed a deeper exploration of early evolutionary steps of the above adaptations. Fungi, and especially budding yeasts, were used intensively to characterize early mutations and chromosomal rearrangements that underlie the acquisition of new adaptive traits allowing them to conquer new ecological niches and potentially leading to speciation. By uncovering the ecological factors and genomic modifications that underline adaptation, these studies showed that Fungi are powerful models for ecological genomics (eco-genomics), and that this approach, so far mainly developed in a few model species, should be expanded to the whole kingdom.}, } @article {pmid24261719, year = {2014}, author = {Wall, D}, title = {Molecular recognition in myxobacterial outer membrane exchange: functional, social and evolutionary implications.}, journal = {Molecular microbiology}, volume = {91}, number = {2}, pages = {209-220}, pmid = {24261719}, issn = {1365-2958}, support = {R01 GM101449/GM/NIGMS NIH HHS/United States ; GM101449/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Outer Membrane Proteins/genetics/*metabolism ; Bacterial Proteins/genetics/*metabolism ; Biological Evolution ; Lipids/*physiology ; *Microbial Interactions ; Myxococcales/genetics/*metabolism ; Protein Transport ; }, abstract = {Through cooperative interactions, bacteria can build multicellular communities. To ensure that productive interactions occur, bacteria must recognize their neighbours and respond accordingly. Molecular recognition between cells is thus a fundamental behaviour, and in bacteria important discoveries have been made. This MicroReview focuses on a recently described recognition system in myxobacteria that is governed by a polymorphic cell surface receptor called TraA. TraA regulates outer membrane exchange (OME), whereby myxobacterial cells transiently fuse their OMs to efficiently transfer proteins and lipids between cells. Unlike other transport systems, OME is rather indiscriminate in what OM goods are transferred. In contrast, the recognition of partnering cells is discriminatory and only occurs between cells that bear identical or closely related TraA proteins. Therefore TraA functions in kin recognition and, in turn, OME helps regulate social interactions between myxobacteria. Here, I discuss and speculate on the social and evolutionary implications of OME and suggest it helps to guide their transition from free-living cells into coherent and functional populations.}, } @article {pmid24261447, year = {2013}, author = {Niklas, KJ and Cobb, ED and Crawford, DR}, title = {The evo-devo of multinucleate cells, tissues, and organisms, and an alternative route to multicellularity.}, journal = {Evolution & development}, volume = {15}, number = {6}, pages = {466-474}, doi = {10.1111/ede.12055}, pmid = {24261447}, issn = {1525-142X}, mesh = {*Biological Evolution ; Cell Division ; Eukaryota/classification/cytology/*genetics/growth & development ; Plants/metabolism ; Viridiplantae/classification/*cytology/*genetics/growth & development ; }, abstract = {Multinucleate cells, tissues, or organisms occur in 60 families of land plants and in five otherwise diverse algal lineages (Rhodophyceae, Xanthophyceae, Chlorophyceae, Ulvophyceae, and Charophyceae). Inspection of a morphospace constructed out of eight developmental processes reveals a large number of possible variants of multinucleate cells and organisms that, with two exceptions, are represented by one or more plant species in one or more clades. Thus, most of these permutations of developmental processes exist in nature. Inspection of the morphospace also shows how the siphonous body plan (a multinucleate cell with the capacity for indeterminate growth in size) can theoretically serve as the direct progenitor of a multicellular organism by a process similar to segregative cell division observed in siphonocladean algae. Using molecular phylogenies of algal clades, different evolutionary scenarios are compared to see how the multicellular condition may have evolved from a multinucleate unicellular progenitor. We also show that the siphonous progenitor of a multicellular organism has previously passed through the alignment-of-fitness phase (in which genetic similarity among cells/nuclei minimizes internal genomic conflict) and the export-of-fitness phase (in which genetically similar cells/nuclei collaborate to achieve a reproductively integrated multicellular organism). All that is theoretically required is the evolutionary acquisition of the capacity to compartmentalize its cytoplasm.}, } @article {pmid24256402, year = {2013}, author = {Gleason, EJ and Kramer, EM}, title = {Conserved roles for Polycomb Repressive Complex 2 in the regulation of lateral organ development in Aquilegia x coerulea 'Origami'.}, journal = {BMC plant biology}, volume = {13}, number = {}, pages = {185}, pmid = {24256402}, issn = {1471-2229}, mesh = {Aquilegia/genetics/*growth & development/*metabolism ; *Conserved Sequence ; *Crosses, Genetic ; Down-Regulation/genetics ; Flowers/anatomy & histology/genetics ; Gene Expression Regulation, Plant ; Gene Silencing ; Genetic Association Studies ; *Organogenesis/genetics ; Phenotype ; Plant Leaves/genetics ; Plant Proteins/metabolism ; Plant Viruses/physiology ; Polycomb Repressive Complex 2/genetics/*metabolism ; }, abstract = {BACKGROUND: Epigenetic regulation is necessary for maintaining gene expression patterns in multicellular organisms. The Polycomb Group (PcG) proteins form several complexes with important and deeply conserved epigenetic functions in both the plant and animal kingdoms. One such complex, the Polycomb Repressive Complex 2 (PRC2), is critical to many developmental processes in plants including the regulation of major developmental transitions. In addition, PRC2 restricts the expression domain of various transcription factor families in Arabidopsis, including the class I KNOX genes and several of the ABCE class MADS box genes. While the functions of these transcription factors are known to be deeply conserved, whether or not their regulation by PRC2 is similarly conserved remains an open question.

RESULTS: Here we use virus-induced gene silencing (VIGS) to characterize the function of the PRC2 complex in lateral organ development of Aquilegia x coerulea 'Origami', a member of the lower eudicot order Ranunculales. Leaves with PRC2 down-regulation displayed a range of phenotypes including ruffled or curled laminae, additional lobing, and an increased frequency of higher order branching. Sepals and petals were also affected, being narrowed, distorted, or, in the case of the sepals, exhibiting partial homeotic transformation. Many of the petal limbs also had a particularly intense yellow coloration due to an accumulation of carotenoid pigments. We show that the A. x coerulea floral MADS box genes AGAMOUS1 (AqAG1), APETALA3-3 (AqAP3-3) and SEPALLATA3 (AqSEP3) are up-regulated in many tissues, while expression of the class I KNOX genes and several candidate genes involved in carotenoid production or degradation are largely unaffected.

CONCLUSIONS: PRC2 targeting of several floral MADS box genes may be conserved in dicots, but other known targets do not appear to be. In the case of the type I KNOX genes, this may reflect a regulatory shift associated with the evolution of compound leaves.}, } @article {pmid24252439, year = {2014}, author = {Ågren, JA}, title = {Evolutionary transitions in individuality: insights from transposable elements.}, journal = {Trends in ecology & evolution}, volume = {29}, number = {2}, pages = {90-96}, doi = {10.1016/j.tree.2013.10.007}, pmid = {24252439}, issn = {1872-8383}, mesh = {Animals ; Arabidopsis/genetics ; Behavior, Animal ; *Biological Evolution ; *DNA Transposable Elements ; Genetic Fitness ; Genome ; Individuality ; Reproduction/genetics ; Selection, Genetic ; Social Behavior ; }, abstract = {The history of life has been characterised by evolutionary transitions in individuality, the grouping together of independently replicating units into new larger wholes: genes to chromosomes, chromosomes in genomes, up to three genomes in cells, and cells in multicellular organisms that form groups and societies. Central to understanding these transitions is to determine what prevents selfish behaviour at lower levels from disrupting the functionality of higher levels. Here, I review work on transposable elements, a common source of disruption at the genome level, in light of the evolutionary transitions framework, and argue that the rapid influx of data on transposons from whole-genome sequencing has created a rich data source to incorporate into the study of evolutionary transitions in individuality.}, } @article {pmid24240534, year = {2013}, author = {Pietra, S and Gustavsson, A and Kiefer, C and Kalmbach, L and Hörstedt, P and Ikeda, Y and Stepanova, AN and Alonso, JM and Grebe, M}, title = {Arabidopsis SABRE and CLASP interact to stabilize cell division plane orientation and planar polarity.}, journal = {Nature communications}, volume = {4}, number = {}, pages = {2779}, pmid = {24240534}, issn = {2041-1723}, mesh = {Alleles ; Amino Acid Sequence ; Arabidopsis/*cytology/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; Base Sequence ; Cell Division/*physiology ; Cell Polarity/physiology ; Chromosomes, Plant ; Gene Expression Regulation, Plant/*physiology ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Microtubule-Associated Proteins/genetics/*metabolism ; Phylogeny ; }, abstract = {The orientation of cell division and the coordination of cell polarity within the plane of the tissue layer (planar polarity) contribute to shape diverse multicellular organisms. The root of Arabidopsis thaliana displays regularly oriented cell divisions, cell elongation and planar polarity providing a plant model system to study these processes. Here we report that the SABRE protein, which shares similarity with proteins of unknown function throughout eukaryotes, has important roles in orienting cell division and planar polarity. SABRE localizes at the plasma membrane, endomembranes, mitotic spindle and cell plate. SABRE stabilizes the orientation of CLASP-labelled preprophase band microtubules predicting the cell division plane, and of cortical microtubules driving cell elongation. During planar polarity establishment, sabre is epistatic to clasp at directing polar membrane domains of Rho-of-plant GTPases. Our findings mechanistically link SABRE to CLASP-dependent microtubule organization, shedding new light on the function of SABRE-related proteins in eukaryotes.}, } @article {pmid24231534, year = {2013}, author = {Griffiths, JG and Bonser, SP}, title = {Is sex advantageous in adverse environments? A test of the abandon-ship hypothesis.}, journal = {The American naturalist}, volume = {182}, number = {6}, pages = {718-725}, doi = {10.1086/673476}, pmid = {24231534}, issn = {1537-5323}, mesh = {Adaptation, Biological ; Animals ; Population Dynamics ; Reproduction ; *Stress, Physiological ; Trifolium/*physiology ; }, abstract = {Understanding the evolution and maintenance of sexual reproduction remains a long-standing challenge in evolutionary biology. Stress often induces sexual reproduction in facultatively sexual species (those species capable of both sexual and asexual reproduction). The abandon-ship hypothesis predicts higher allocation to sex under stress to allow low-fitness individuals to recombine their genotype, potentially increasing offspring fitness. However, effective tests of the abandon-ship hypothesis, particularly in multicellular organisms, are lacking. Here we test the abandon-ship hypothesis, using cyanogenic and acyanogenic defense phenotypes of the short-lived perennial herb Trifolium repens. Cyanogenesis provides an effective defense against herbivores and is under relatively simple genetic control (plants dominant for cyanogenesis at two alleles express the defended phenotype). Thus, maladapted individuals can acquire adaptive defense alleles for their offspring in a single episode of sexual reproduction. Plants were grown under high- and low-herbivory treatments (plants were exposed to herbivorous snails) and a control treatment (no herbivory). Herbivores reduced growth and fitness in all treated plants, but herbivory induced higher sexual allocation only in maladapted (acyanogenic) individuals. Overall, our results support the abandon-ship hypothesis.}, } @article {pmid24229212, year = {2013}, author = {Holbek, S and Bendtsen, KM and Juul, J}, title = {Moderate stem-cell telomere shortening rate postpones cancer onset in a stochastic model.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {88}, number = {4}, pages = {042706}, doi = {10.1103/PhysRevE.88.042706}, pmid = {24229212}, issn = {1550-2376}, mesh = {Aging/genetics/pathology ; Cell Cycle/genetics ; *Models, Biological ; Neoplasms/*genetics/*pathology ; Stem Cells/*metabolism ; Stochastic Processes ; Telomere/genetics ; *Telomere Shortening ; }, abstract = {Mammalian cells are restricted from proliferating indefinitely. Telomeres at the end of each chromosome are shortened at cell division and when they reach a critical length, the cell will enter permanent cell cycle arrest-a state known as senescence. This mechanism is thought to be tumor suppressing, as it helps prevent precancerous cells from dividing uncontrollably. Stem cells express the enzyme telomerase, which elongates the telomeres, thereby postponing senescence. However, unlike germ cells and most types of cancer cells, stem cells only express telomerase at levels insufficient to fully maintain the length of their telomeres, leading to a slow decline in proliferation potential. It is not yet fully understood how this decline influences the risk of cancer and the longevity of the organism. We here develop a stochastic model to explore the role of telomere dynamics in relation to both senescence and cancer. The model describes the accumulation of cancerous mutations in a multicellular organism and creates a coherent theoretical framework for interpreting the results of several recent experiments on telomerase regulation. We demonstrate that the longest average cancer-free lifespan before cancer onset is obtained when stem cells start with relatively long telomeres that are shortened at a steady rate at cell division. Furthermore, the risk of cancer early in life can be reduced by having a short initial telomere length. Finally, our model suggests that evolution will favor a shorter than optimal average cancer-free lifespan in order to postpone cancer onset until late in life.}, } @article {pmid24228734, year = {2013}, author = {Adrian, AB and Comeron, JM}, title = {The Drosophila early ovarian transcriptome provides insight to the molecular causes of recombination rate variation across genomes.}, journal = {BMC genomics}, volume = {14}, number = {}, pages = {794}, pmid = {24228734}, issn = {1471-2164}, support = {RC2GM092501/GM/NIGMS NIH HHS/United States ; T32 GM082729/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Chromatin/genetics ; *DNA Breaks, Double-Stranded ; Drosophila melanogaster/genetics ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genome, Insect ; Meiosis/*genetics ; Ovary/metabolism ; *Recombination, Genetic ; }, abstract = {BACKGROUND: Evidence in yeast indicates that gene expression is correlated with recombination activity and double-strand break (DSB) formation in some hotspots. Studies of nucleosome occupancy in yeast and mice also suggest that open chromatin influences the formation of DSBs. In Drosophila melanogaster, high-resolution recombination maps show an excess of DSBs within annotated transcripts relative to intergenic sequences. The impact of active transcription on recombination landscapes, however, remains unexplored in a multicellular organism. We then investigated the transcription profile during early meiosis in D. melanogaster females to obtain a glimpse at the relevant transcriptional dynamics during DSB formation, and test the specific hypothesis that DSBs preferentially target transcriptionally active genomic regions.

RESULTS: Our study of transcript profiles of early- and late-meiosis using mRNA-seq revealed, 1) significant differences in gene expression, 2) new genes and exons, 3) parent-of-origin effects on transcription in early-meiosis stages, and 4) a nonrandom genomic distribution of transcribed genes. Importantly, genomic regions that are more actively transcribed during early meiosis show higher rates of recombination, and we ruled out DSB preference for genic regions that are not transcribed.

CONCLUSIONS: Our results provide evidence in a multicellular organism that transcription during the initial phases of meiosis increases the likelihood of DSB and give insight into the molecular determinants of recombination rate variation across the D. melanogaster genome. We propose that a model where variation in gene expression plays a role altering the recombination landscape across the genome could provide a molecular, heritable and plastic mechanism to observed patterns of recombination variation, from the high level of intra-specific variation to the known influence of environmental factors and stress conditions.}, } @article {pmid24226773, year = {2013}, author = {Arpaia, N and Campbell, C and Fan, X and Dikiy, S and van der Veeken, J and deRoos, P and Liu, H and Cross, JR and Pfeffer, K and Coffer, PJ and Rudensky, AY}, title = {Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.}, journal = {Nature}, volume = {504}, number = {7480}, pages = {451-455}, pmid = {24226773}, issn = {1476-4687}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R37 AI034206/AI/NIAID NIH HHS/United States ; T32 GM007739/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R37AI034206/AI/NIAID NIH HHS/United States ; T32A1007621//PHS HHS/United States ; T32 CA009149/CA/NCI NIH HHS/United States ; T32 AI007621/AI/NIAID NIH HHS/United States ; }, mesh = {Acetylation ; Animals ; Butyrates/*metabolism ; *Cell Differentiation ; Cytokines/metabolism ; Dendritic Cells/immunology/metabolism ; Enhancer Elements, Genetic/genetics ; Fermentation ; Forkhead Transcription Factors/genetics/metabolism ; Histone Deacetylases/metabolism ; Inflammation Mediators/metabolism ; Intestinal Mucosa/cytology/immunology/*metabolism/microbiology ; Intestines/cytology/immunology/*microbiology ; Introns/genetics ; Lymphocyte Count ; Male ; Mice ; Mice, Inbred C57BL ; Starch/metabolism ; *Symbiosis ; T-Lymphocytes, Regulatory/*cytology/immunology/*metabolism ; }, abstract = {Intestinal microbes provide multicellular hosts with nutrients and confer resistance to infection. The delicate balance between pro- and anti-inflammatory mechanisms, essential for gut immune homeostasis, is affected by the composition of the commensal microbial community. Regulatory T cells (Treg cells) expressing transcription factor Foxp3 have a key role in limiting inflammatory responses in the intestine. Although specific members of the commensal microbial community have been found to potentiate the generation of anti-inflammatory Treg or pro-inflammatory T helper 17 (TH17) cells, the molecular cues driving this process remain elusive. Considering the vital metabolic function afforded by commensal microorganisms, we reasoned that their metabolic by-products are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells. We tested this hypothesis by exploring the effect of microbial metabolites on the generation of anti-inflammatory Treg cells. We found that in mice a short-chain fatty acid (SCFA), butyrate, produced by commensal microorganisms during starch fermentation, facilitated extrathymic generation of Treg cells. A boost in Treg-cell numbers after provision of butyrate was due to potentiation of extrathymic differentiation of Treg cells, as the observed phenomenon was dependent on intronic enhancer CNS1 (conserved non-coding sequence 1), essential for extrathymic but dispensable for thymic Treg-cell differentiation. In addition to butyrate, de novo Treg-cell generation in the periphery was potentiated by propionate, another SCFA of microbial origin capable of histone deacetylase (HDAC) inhibition, but not acetate, which lacks this HDAC-inhibitory activity. Our results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms.}, } @article {pmid24222650, year = {2014}, author = {Bertrand, S and Iwema, T and Escriva, H}, title = {FGF signaling emerged concomitantly with the origin of Eumetazoans.}, journal = {Molecular biology and evolution}, volume = {31}, number = {2}, pages = {310-318}, doi = {10.1093/molbev/mst222}, pmid = {24222650}, issn = {1537-1719}, mesh = {Amino Acid Sequence ; Animals ; Eukaryota/classification/*metabolism ; Evolution, Molecular ; Fibroblast Growth Factors/chemistry/*genetics/metabolism ; Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Receptors, Fibroblast Growth Factor/metabolism ; Sequence Alignment ; *Signal Transduction ; }, abstract = {Complex metazoan bodies require cell-to-cell communication for development, a process often mediated by signaling molecules binding to specific receptors. Relatively few signaling pathways have been recruited during evolution to build multicellular animals from unicellular zygotes. Of these few signaling pathways, one of particular importance is the receptor tyrosine kinase (RTK) pathway. In metazoans, fibroblast growth factors (FGFs) bind to receptors in the RTK family, but the origin of the FGF gene family has so far remained a mystery. Here we show that extant bona fide FGFs most likely originated from proteins bearing an FGF-like domain that arose in a choanoflagellate/metazoan ancestor. We found orthologous genes closely related to FGF in choanoflagellates as well as in many metazoans such as sponges, acoels, protostomes, or nonvertebrate deuterostomes. We also show that these genes have a common evolutionary history with Retinitis Pigmentosa 1 (RP1). Even if some metazoan signaling pathways emerged long before multicellularity, we show that FGFs, like their receptors, originated in a eumetazoan ancestor.}, } @article {pmid24218634, year = {2013}, author = {Harmston, N and Baresic, A and Lenhard, B}, title = {The mystery of extreme non-coding conservation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {368}, number = {1632}, pages = {20130021}, pmid = {24218634}, issn = {1471-2970}, support = {MC_UP_1102/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Conserved Sequence/*genetics ; DNA, Intergenic/*genetics ; *Evolution, Molecular ; Genome/*genetics ; *Models, Genetic ; Selection, Genetic ; }, abstract = {Regions of several dozen to several hundred base pairs of extreme conservation have been found in non-coding regions in all metazoan genomes. The distribution of these elements within and across genomes has suggested that many have roles as transcriptional regulatory elements in multi-cellular organization, differentiation and development. Currently, there is no known mechanism or function that would account for this level of conservation at the observed evolutionary distances. Previous studies have found that, while these regions are under strong purifying selection, and not mutational coldspots, deletion of entire regions in mice does not necessarily lead to identifiable changes in phenotype during development. These opposing findings lead to several questions regarding their functional importance and why they are under strong selection in the first place. In this perspective, we discuss the methods and techniques used in identifying and dissecting these regions, their observed patterns of conservation, and review the current hypotheses on their functional significance.}, } @article {pmid24213153, year = {2014}, author = {Lenartowski, R and Suwińska, A and Prusińska, J and Gumowski, K and Lenartowska, M}, title = {Molecular cloning and transcriptional activity of a new Petunia calreticulin gene involved in pistil transmitting tract maturation, progamic phase, and double fertilization.}, journal = {Planta}, volume = {239}, number = {2}, pages = {437-454}, pmid = {24213153}, issn = {1432-2048}, mesh = {Amino Acid Sequence ; Base Sequence ; Calcium/*metabolism ; Calcium-Binding Proteins/genetics/metabolism ; Calreticulin/*genetics/metabolism ; DNA, Complementary/chemistry/genetics ; DNA, Plant/chemistry/genetics ; Flowers/cytology/genetics/physiology ; Gene Expression ; *Gene Expression Regulation, Plant ; Homeostasis ; Molecular Sequence Data ; Petunia/cytology/*genetics/physiology ; Phylogeny ; Plant Proteins/genetics/metabolism ; Pollen/cytology/genetics/physiology ; Pollination ; Protein Structure, Tertiary ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {Calreticulin (CRT) is a highly conserved and ubiquitously expressed Ca[2+]-binding protein in multicellular eukaryotes. As an endoplasmic reticulum-resident protein, CRT plays a key role in many cellular processes including Ca[2+] storage and release, protein synthesis, and molecular chaperoning in both animals and plants. CRT has long been suggested to play a role in plant sexual reproduction. To begin to address this possibility, we cloned and characterized the full-length cDNA of a new CRT gene (PhCRT) from Petunia. The deduced amino acid sequence of PhCRT shares homology with other known plant CRTs, and phylogenetic analysis indicates that the PhCRT cDNA clone belongs to the CRT1/CRT2 subclass. Northern blot analysis and fluorescent in situ hybridization were used to assess PhCRT gene expression in different parts of the pistil before pollination, during subsequent stages of the progamic phase, and at fertilization. The highest level of PhCRT mRNA was detected in the stigma-style part of the unpollinated pistil 1 day before anthesis and during the early stage of the progamic phase, when pollen is germinated and tubes outgrow on the stigma. In the ovary, PhCRT mRNA was most abundant after pollination and reached maximum at the late stage of the progamic phase, when pollen tubes grow into the ovules and fertilization occurs. PhCRT mRNA transcripts were seen to accumulate predominantly in transmitting tract cells of maturing and receptive stigma, in germinated pollen/growing tubes, and at the micropylar region of the ovule, where the female gametophyte is located. From these results, we suggest that PhCRT gene expression is up-regulated during secretory activity of the pistil transmitting tract cells, pollen germination and outgrowth of the tubes, and then during gamete fusion and early embryogenesis.}, } @article {pmid24210433, year = {2013}, author = {Miller, PW and Clarke, DN and Weis, WI and Lowe, CJ and Nelson, WJ}, title = {The evolutionary origin of epithelial cell-cell adhesion mechanisms.}, journal = {Current topics in membranes}, volume = {72}, number = {}, pages = {267-311}, pmid = {24210433}, issn = {1063-5823}, support = {U01 GM094663/GM/NIGMS NIH HHS/United States ; R01 GM035527/GM/NIGMS NIH HHS/United States ; GM007276/GM/NIGMS NIH HHS/United States ; T32 GM007276/GM/NIGMS NIH HHS/United States ; R37 GM035527/GM/NIGMS NIH HHS/United States ; GM035527/GM/NIGMS NIH HHS/United States ; R01 GM056169/GM/NIGMS NIH HHS/United States ; GM56169/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/chemistry/metabolism ; Allosteric Regulation ; Animals ; *Biological Evolution ; Cadherins/genetics/metabolism ; Caenorhabditis elegans/metabolism ; Cell Adhesion ; Chickens/metabolism ; Dictyostelium/metabolism ; Drosophila/metabolism ; Epithelial Cells/cytology/*metabolism ; Extracellular Matrix/metabolism ; Genome ; Mammals/metabolism ; Protein Binding ; Protein Isoforms/chemistry/genetics/metabolism ; Protein Structure, Tertiary ; Xenopus laevis/metabolism ; Zebrafish/metabolism ; }, abstract = {A simple epithelium forms a barrier between the outside and the inside of an organism, and is the first organized multicellular tissue found in evolution. We examine the relationship between the evolution of epithelia and specialized cell-cell adhesion proteins comprising the classical cadherin/β-catenin/α-catenin complex (CCC). A review of the divergent functional properties of the CCC in metazoans and non-metazoans, and an updated phylogenetic coverage of the CCC using recent genomic data reveal: (1) The core CCC likely originated before the last common ancestor of unikonts and their closest bikont sister taxa. (2) Formation of the CCC may have constrained sequence evolution of the classical cadherin cytoplasmic domain and β-catenin in metazoa. (3) The α-catenin-binding domain in β-catenin appears to be the favored mutation site for disrupting β-catenin function in the CCC. (4) The ancestral function of the α/β-catenin heterodimer appears to be an actin-binding module. In some metazoan groups, more complex functions of α-catenin were gained by sequence divergence in the non-actin-binding (N-, M-) domains. (5) Allosteric regulation of α-catenin may have evolved for more complex regulation of the actin cytoskeleton.}, } @article {pmid24200356, year = {2013}, author = {Villa, F and Villa, S and Gelain, A and Cappitelli, F}, title = {Sub-lethal activity of small molecules from natural sources and their synthetic derivatives against biofilm forming nosocomial pathogens.}, journal = {Current topics in medicinal chemistry}, volume = {13}, number = {24}, pages = {3184-3204}, doi = {10.2174/15680266113136660225}, pmid = {24200356}, issn = {1873-4294}, mesh = {Anti-Bacterial Agents/chemical synthesis/*chemistry/*pharmacology ; Aquatic Organisms ; Bacteria/chemistry ; Biofilms/drug effects ; Biological Products/chemistry ; Computer Simulation ; Cross Infection/drug therapy/*microbiology ; Drug Design ; High-Throughput Screening Assays/*methods ; Humans ; Plant Extracts/chemistry/pharmacology ; Small Molecule Libraries/*chemical synthesis/*pharmacology ; }, abstract = {Nowadays, the patient safety is seriously jeopardized by the emergence and spread of nosocomial pathogens in the form of biofilm that is resistant to traditional and affordable antimicrobials. Although advances in organic synthesis have extended the lifetime of classic antibiotics through synthetic modifications, the search of innovative antibiofilm compounds from natural sources can provide new templates, novel targets and unique mechanisms that should have advantages over known antimicrobial agents. Testing sub-lethal concentrations of crude extracts and/or isolated compounds from plants and microorganisms is critical to acting on mechanisms subtler than the killing activity, e.g. those influencing the multicellular behavior, offering an elegant way to develop novel antimicrobial-free antibiofilm strategies. Herein we discussed the search and biological activity of small molecules from natural sources and their synthetic derivatives able to modulate biofilm genesis of nosocomial pathogens through non-microbicidal mechanisms (sub-lethal concentrations). The present work offers an overview about the approaches applied to the discovery of lead small molecules including a) conventional drug design methods like screening of chemical compounds obtained from nature and b) computer- aided drug design approaches. Finally, a classification (not exhaustive but representative) based on the natural origin of small molecules and their synthetic derivatives was reported. The information presented in this review should be of interest to a broad range of disciplines and represents an effort to summarize experimental research and advances in this field.}, } @article {pmid24196322, year = {2014}, author = {Abreu, F and Morillo, V and Nascimento, FF and Werneck, C and Cantão, ME and Ciapina, LP and de Almeida, LG and Lefèvre, CT and Bazylinski, DA and de Vasconcelos, AT and Lins, U}, title = {Deciphering unusual uncultured magnetotactic multicellular prokaryotes through genomics.}, journal = {The ISME journal}, volume = {8}, number = {5}, pages = {1055-1068}, pmid = {24196322}, issn = {1751-7370}, mesh = {*Biological Evolution ; Deltaproteobacteria/*cytology/*genetics/growth & development/physiology ; Genomics ; Phylogeny ; }, abstract = {Candidatus Magnetoglobus multicellularis (Ca. M. multicellularis) is a member of a group of uncultured magnetotactic prokaryotes that possesses a unique multicellular morphology. To better understand this organism's physiology, we used a genomic approach through pyrosequencing. Genomic data analysis corroborates previous structural studies and reveals the proteins that are likely involved in multicellular morphogenesis of this microorganism. Interestingly, some detected protein sequences that might be involved in cell adhesion are homologues to phylogenetically unrelated filamentous multicellular bacteria proteins, suggesting their contribution in the early development of multicellular organization in Bacteria. Genes related to the behavior of Ca. M. multicellularis (chemo-, photo- and magnetotaxis) and its metabolic capabilities were analyzed. On the basis of the genomic-physiologic information, enrichment media were tested. One medium supported chemoorganoheterotrophic growth of Ca. M. multicellularis and allowed the microorganisms to maintain their multicellular morphology and cell cycle, confirming for the first time that the entire life cycle of the MMP occurs in a multicellular form. Because Ca. M. multicellularis has a unique multicellular life style, its cultivation is an important achievement for further studies regarding the multicellular evolution in prokaryotes.}, } @article {pmid24195722, year = {2013}, author = {Zaritsky, A and Manor, N and Wolf, L and Ben-Jacob, E and Tsarfaty, I}, title = {Benchmark for multi-cellular segmentation of bright field microscopy images.}, journal = {BMC bioinformatics}, volume = {14}, number = {}, pages = {319}, pmid = {24195722}, issn = {1471-2105}, mesh = {Algorithms ; Animals ; Cell Movement/*physiology ; Cytological Techniques/*methods/standards ; Dogs ; HEK293 Cells ; Humans ; Image Processing, Computer-Assisted/*methods/standards ; Madin Darby Canine Kidney Cells ; Microscopy/*methods/standards ; }, abstract = {BACKGROUND: Multi-cellular segmentation of bright field microscopy images is an essential computational step when quantifying collective migration of cells in vitro. Despite the availability of various tools and algorithms, no publicly available benchmark has been proposed for evaluation and comparison between the different alternatives.

DESCRIPTION: A uniform framework is presented to benchmark algorithms for multi-cellular segmentation in bright field microscopy images. A freely available set of 171 manually segmented images from diverse origins was partitioned into 8 datasets and evaluated on three leading designated tools.

CONCLUSIONS: The presented benchmark resource for evaluating segmentation algorithms of bright field images is the first public annotated dataset for this purpose. This annotated dataset of diverse examples allows fair evaluations and comparisons of future segmentation methods. Scientists are encouraged to assess new algorithms on this benchmark, and to contribute additional annotated datasets.}, } @article {pmid24193369, year = {2013}, author = {Ratcliff, WC and Herron, MD and Howell, K and Pentz, JT and Rosenzweig, F and Travisano, M}, title = {Experimental evolution of an alternating uni- and multicellular life cycle in Chlamydomonas reinhardtii.}, journal = {Nature communications}, volume = {4}, number = {}, pages = {2742}, pmid = {24193369}, issn = {2041-1723}, mesh = {Animals ; *Biological Evolution ; Chlamydomonas reinhardtii/*cytology/*genetics/physiology ; Molecular Sequence Data ; }, abstract = {The transition to multicellularity enabled the evolution of large, complex organisms, but early steps in this transition remain poorly understood. Here we show that multicellular complexity, including development from a single cell, can evolve rapidly in a unicellular organism that has never had a multicellular ancestor. We subject the alga Chlamydomonas reinhardtii to conditions that favour multicellularity, resulting in the evolution of a multicellular life cycle in which clusters reproduce via motile unicellular propagules. While a single-cell genetic bottleneck during ontogeny is widely regarded as an adaptation to limit among-cell conflict, its appearance very early in this transition suggests that it did not evolve for this purpose. Instead, we find that unicellular propagules are adaptive even in the absence of intercellular conflict, maximizing cluster-level fecundity. These results demonstrate that the unicellular bottleneck, a trait essential for evolving multicellular complexity, can arise rapidly via co-option of the ancestral unicellular form.}, } @article {pmid24191137, year = {2013}, author = {Bianca, C}, title = {Controllability in hybrid kinetic equations modeling nonequilibrium multicellular systems.}, journal = {TheScientificWorldJournal}, volume = {2013}, number = {}, pages = {274719}, pmid = {24191137}, issn = {1537-744X}, mesh = {Kinetics ; *Models, Biological ; }, abstract = {This paper is concerned with the derivation of hybrid kinetic partial integrodifferential equations that can be proposed for the mathematical modeling of multicellular systems subjected to external force fields and characterized by nonconservative interactions. In order to prevent an uncontrolled time evolution of the moments of the solution, a control operator is introduced which is based on the Gaussian thermostat. Specifically, the analysis shows that the moments are solution of a Riccati-type differential equation.}, } @article {pmid24188247, year = {2013}, author = {Costantini, M and Alvarez-Valin, F and Costantini, S and Cammarano, R and Bernardi, G}, title = {Compositional patterns in the genomes of unicellular eukaryotes.}, journal = {BMC genomics}, volume = {14}, number = {}, pages = {755}, pmid = {24188247}, issn = {1471-2164}, mesh = {Base Composition ; DNA/chemistry/metabolism ; Eukaryota/classification/*genetics ; *Genome ; Isochores/chemistry/genetics ; Models, Genetic ; Phylogeny ; }, abstract = {BACKGROUND: The genomes of multicellular eukaryotes are compartmentalized in mosaics of isochores, large and fairly homogeneous stretches of DNA that belong to a small number of families characterized by different average GC levels, by different gene concentration (that increase with GC), different chromatin structures, different replication timing in the cell cycle, and other different properties. A question raised by these basic results concerns how far back in evolution the compartmentalized organization of the eukaryotic genomes arose.

RESULTS: In the present work we approached this problem by studying the compositional organization of the genomes from the unicellular eukaryotes for which full sequences are available, the sample used being representative. The average GC levels of the genomes from unicellular eukaryotes cover an extremely wide range (19%-60% GC) and the compositional patterns of individual genomes are extremely different but all genomes tested show a compositional compartmentalization.

CONCLUSIONS: The average GC range of the genomes of unicellular eukaryotes is very broad (as broad as that of prokaryotes) and individual compositional patterns cover a very broad range from very narrow to very complex. Both features are not surprising for organisms that are very far from each other both in terms of phylogenetic distances and of environmental life conditions. Most importantly, all genomes tested, a representative sample of all supergroups of unicellular eukaryotes, are compositionally compartmentalized, a major difference with prokaryotes.}, } @article {pmid24184688, year = {2014}, author = {Päri, M and Kuusksalu, A and Lopp, A and Kjaer, KH and Justesen, J and Kelve, M}, title = {Enzymatically active 2',5'-oligoadenylate synthetases are widely distributed among Metazoa, including protostome lineage.}, journal = {Biochimie}, volume = {97}, number = {}, pages = {200-209}, doi = {10.1016/j.biochi.2013.10.015}, pmid = {24184688}, issn = {1638-6183}, mesh = {2',5'-Oligoadenylate Synthetase/*classification/genetics/metabolism ; Ambystoma mexicanum/classification/genetics/*metabolism ; Amino Acid Sequence ; Animals ; Biological Evolution ; Choanoflagellata/classification/*enzymology/genetics ; Molecular Sequence Data ; Mytilus/classification/*enzymology/genetics ; Nucleotidyltransferases/classification/genetics/metabolism ; *Phylogeny ; Porifera/classification/*enzymology/genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {2',5'-Oligoadenylate synthetases (OASs) belong to the nucleotidyl transferase family together with poly(A) polymerases, CCA-adding enzymes and the recently discovered cyclic-GMP-AMP synthase (cGAS). Mammalian OASs have been thoroughly characterized as components of the interferon-induced antiviral system. The OAS activity and the respective genes were also discovered in marine sponges where the interferon system is absent. In this study the recombinant OASs from several multicellular animals and their closest unicellular relative, a choanoflagellate, were expressed in a bacterial expression system and their enzymatic activities were examined. We demonstrated 2-5A synthesizing activities of OASs from the marine sponge Tedania ignis, a representative of the phylogenetically oldest metazoan phylum (Porifera), from an invertebrate of the protostome lineage, the mollusk Mytilus californianus (Mollusca), and from a vertebrate species, a cartilaginous fish Leucoraja erinacea (Chordata). However, the expressed proteins from an amphibian, the salamander Ambystoma mexicanum (Chordata), and from a protozoan, the marine choanoflagellate Monosiga brevicollis (Choanozoa), did not show 2-5A synthesizing activity. Differently from other studied OASs, OAS from the marine sponge T. ignis was able to catalyze the formation of oligomers having both 2',5'- and 3',5'-phosphodiester linkages. Our data suggest that OASs from sponges and evolutionarily higher animals have similar activation mechanisms which still include different affinities and possibly different structural requirements for the activating RNAs. Considering their 2'- and 3'-specificities, sponge OASs could represent a link between evolutionarily earlier nucleotidyl transferases and 2'-specific OASs from higher animals.}, } @article {pmid24153409, year = {2014}, author = {Phatarphekar, A and Buss, JM and Rokita, SE}, title = {Iodotyrosine deiodinase: a unique flavoprotein present in organisms of diverse phyla.}, journal = {Molecular bioSystems}, volume = {10}, number = {1}, pages = {86-92}, pmid = {24153409}, issn = {1742-2051}, support = {R01 DK084186/DK/NIDDK NIH HHS/United States ; T32 GM080189/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Catalytic Domain ; Diiodotyrosine/metabolism ; Evolution, Molecular ; Gene Expression Regulation, Enzymologic ; Halogenation ; Iodide Peroxidase/chemistry/*genetics/*metabolism ; Iodides/metabolism ; Mice ; Protein Conformation ; Thyroid Hormones/*biosynthesis ; Tyrosine/*metabolism ; }, abstract = {Iodide is required for thyroid hormone synthesis in mammals and other vertebrates. The role of both iodide and iodinated tyrosine derivatives is currently unknown in lower organisms, yet the presence of a key enzyme in iodide conservation, iodotyrosine deiodinase (IYD), is suggested by genomic data from a wide range of multicellular organisms as well as some bacteria. A representative set of these genes has now been expressed, and the resulting enzymes all catalyze reductive deiodination of diiodotyrosine with kcat/Km values within a single order of magnitude. This implies a physiological presence of iodotyrosines (or related halotyrosines) and a physiological role for their turnover. At least for Metazoa, IYD should provide a new marker for tracing the evolutionary development of iodinated amino acids as regulatory signals through the tree of life.}, } @article {pmid24147855, year = {2014}, author = {Svoronos, AA and Tejavibulya, N and Schell, JY and Shenoy, VB and Morgan, JR}, title = {Micro-mold design controls the 3D morphological evolution of self-assembling multicellular microtissues.}, journal = {Tissue engineering. Part A}, volume = {20}, number = {7-8}, pages = {1134-1144}, pmid = {24147855}, issn = {1937-335X}, support = {R01EB008664/EB/NIBIB NIH HHS/United States ; }, mesh = {Equipment Design ; Fibroblasts/drug effects ; Humans ; Tissue Engineering/*instrumentation/*methods ; Transforming Growth Factor beta1/pharmacology ; }, abstract = {When seeded into nonadhesive micro-molds, cells self-assemble three-dimensional (3D) multicellular microtissues via the action of cytoskeletal-mediated contraction and cell-cell adhesion. The size and shape of the tissue is a function of the cell type and the size, shape, and obstacles of the micro-mold. In this article, we used human fibroblasts to investigate some of the elements of mold design and how they can be used to guide the morphological changes that occur as a 3D tissue self-organizes. In a loop-ended dogbone mold with two nonadhesive posts, fibroblasts formed a self-constrained tissue whose tension induced morphological changes that ultimately caused the tissue to thin and rupture. Increasing the width of the dogbone's connecting rod increased the stability, whereas increasing its length decreased the stability. Mapping the rupture points showed that the balance of cell volume between the toroid and connecting rod regions of the dogbone tissue controlled the point of rupture. When cells were treated with transforming growth factor-β1, dogbones ruptured sooner due to increased cell contraction. In mold designs to form tissues with more complex shapes such as three interconnected toroids or a honeycomb, obstacle design controlled tension and tissue morphology. When the vertical posts were changed to cones, they became tension modulators that dictated when and where tension was released in a large self-organizing tissue. By understanding how elements of mold design control morphology, we can produce better models to study organogenesis, examine 3D cell mechanics, and fabricate building parts for tissue engineering.}, } @article {pmid24145419, year = {2013}, author = {Oud, B and Guadalupe-Medina, V and Nijkamp, JF and de Ridder, D and Pronk, JT and van Maris, AJ and Daran, JM}, title = {Genome duplication and mutations in ACE2 cause multicellular, fast-sedimenting phenotypes in evolved Saccharomyces cerevisiae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {45}, pages = {E4223-31}, pmid = {24145419}, issn = {1091-6490}, mesh = {Benzenesulfonates ; Chitinases ; DNA-Binding Proteins/*genetics ; *Directed Molecular Evolution ; Flow Cytometry ; Frameshift Mutation/genetics ; Gene Duplication/*genetics ; Genetic Engineering/*methods ; *Phenotype ; Reverse Transcriptase Polymerase Chain Reaction ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/*genetics ; Sequence Analysis, DNA ; Transcription Factors/*genetics ; }, abstract = {Laboratory evolution of the yeast Saccharomyces cerevisiae in bioreactor batch cultures yielded variants that grow as multicellular, fast-sedimenting clusters. Knowledge of the molecular basis of this phenomenon may contribute to the understanding of natural evolution of multicellularity and to manipulating cell sedimentation in laboratory and industrial applications of S. cerevisiae. Multicellular, fast-sedimenting lineages obtained from a haploid S. cerevisiae strain in two independent evolution experiments were analyzed by whole genome resequencing. The two evolved cell lines showed different frameshift mutations in a stretch of eight adenosines in ACE2, which encodes a transcriptional regulator involved in cell cycle control and mother-daughter cell separation. Introduction of the two ace2 mutant alleles into the haploid parental strain led to slow-sedimenting cell clusters that consisted of just a few cells, thus representing only a partial reconstruction of the evolved phenotype. In addition to single-nucleotide mutations, a whole-genome duplication event had occurred in both evolved multicellular strains. Construction of a diploid reference strain with two mutant ace2 alleles led to complete reconstruction of the multicellular-fast sedimenting phenotype. This study shows that whole-genome duplication and a frameshift mutation in ACE2 are sufficient to generate a fast-sedimenting, multicellular phenotype in S. cerevisiae. The nature of the ace2 mutations and their occurrence in two independent evolution experiments encompassing fewer than 500 generations of selective growth suggest that switching between unicellular and multicellular phenotypes may be relevant for competitiveness of S. cerevisiae in natural environments.}, } @article {pmid24142536, year = {2013}, author = {Schaible, R and Sussman, M}, title = {FOXO in aging: did evolutionary diversification of FOXO function distract it from prolonging life?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {12}, pages = {1101-1110}, doi = {10.1002/bies.201300078}, pmid = {24142536}, issn = {1521-1878}, mesh = {Aging/genetics/*physiology ; Animals ; Evolution, Molecular ; Forkhead Transcription Factors/genetics/*physiology ; Humans ; Longevity/genetics/*physiology ; }, abstract = {In this paper we contrast the simple role of FOXO in the seemingly non-aging Hydra with its more diversified function in multicellular eukaryotes that manifest aging and limited life spans. From this comparison we develop the concept that, whilst once devoted to life-prolonging cell-renewal (in Hydra), evolutionary accumulation of coupled functionality in FOXO has since 'distracted' it from this role. Seen in this light, aging may not be the direct cost of competing functions, such as reproduction or growth, but the result of a shift in emphasis in a protein, which is accompanied by advantages such as greater organismal complexity and adaptability, but also disadvantages such as reduced regeneration capacity. Studying the role of FOXO in non-aging organisms might, therefore, illuminate the path to extend life span in aging organisms.}, } @article {pmid24139735, year = {2013}, author = {Yant, L and Hollister, JD and Wright, KM and Arnold, BJ and Higgins, JD and Franklin, FCH and Bomblies, K}, title = {Meiotic adaptation to genome duplication in Arabidopsis arenosa.}, journal = {Current biology : CB}, volume = {23}, number = {21}, pages = {2151-2156}, pmid = {24139735}, issn = {1879-0445}, support = {1 F32 GM105293/GM/NIGMS NIH HHS/United States ; 1 F32 GM096699/GM/NIGMS NIH HHS/United States ; F32 GM105293/GM/NIGMS NIH HHS/United States ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; F32 GM096699/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/*genetics/metabolism ; Chromosome Segregation ; *Evolution, Molecular ; *Genome, Plant ; Genome-Wide Association Study ; *Meiosis ; Molecular Sequence Data ; *Polyploidy ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Whole genome duplication (WGD) is a major factor in the evolution of multicellular eukaryotes, yet by doubling the number of homologs, WGD severely challenges reliable chromosome segregation, a process conserved across kingdoms. Despite this, numerous genome-duplicated (polyploid) species persist in nature, indicating early problems can be overcome. Little is known about which genes are involved--only one has been molecularly characterized. To gain new insights into the molecular basis of adaptation to polyploidy, we investigated genome-wide patterns of differentiation between natural diploids and tetraploids of Arabidopsis arenosa, an outcrossing relative of A. thaliana. We first show that diploids are not preadapted to polyploid meiosis. We then use a genome scanning approach to show that although polymorphism is extensively shared across ploidy levels, there is strong ploidy-specific differentiation in 39 regions spanning 44 genes. These are discrete, mostly single-gene peaks of sharply elevated differentiation. Among these peaks are eight meiosis genes whose encoded proteins coordinate a specific subset of early meiotic functions, suggesting these genes comprise a polygenic solution to WGD-associated chromosome segregation challenges. Our findings indicate that even conserved meiotic processes can be capable of nimble evolutionary shifts when required.}, } @article {pmid24133452, year = {2013}, author = {Mohanty, A and McBride, HM}, title = {Emerging roles of mitochondria in the evolution, biogenesis, and function of peroxisomes.}, journal = {Frontiers in physiology}, volume = {4}, number = {}, pages = {268}, pmid = {24133452}, issn = {1664-042X}, abstract = {In the last century peroxisomes were thought to have an endosymbiotic origin. Along with mitochondria and chloroplasts, peroxisomes primarily regulate their numbers through the growth and division of pre-existing organelles, and they house specific machinery for protein import. These features were considered unique to endosymbiotic organelles, prompting the idea that peroxisomes were key cellular elements that helped facilitate the evolution of multicellular organisms. The functional similarities to mitochondria within mammalian systems expanded these ideas, as both organelles scavenge peroxide and reactive oxygen species, both organelles oxidize fatty acids, and at least in higher eukaryotes, the biogenesis of both organelles is controlled by common nuclear transcription factors of the PPAR family. Over the last decade it has been demonstrated that the fission machinery of both organelles is also shared, and that both organelles act as critical signaling platforms for innate immunity and other pathways. Taken together it is clear that the mitochondria and peroxisomes are functionally coupled, regulating cellular metabolism and signaling through a number of common mechanisms. However, recent work has focused primarily on the role of the ER in the biogenesis of peroxisomes, potentially overshadowing the critical importance of the mitochondria as a functional partner. In this review, we explore the mechanisms of functional coupling of the peroxisomes to the mitochondria/ER networks, providing some new perspectives on the potential contribution of the mitochondria to peroxisomal biogenesis.}, } @article {pmid24130559, year = {2013}, author = {Eri, R and Chieppa, M}, title = {Messages from the Inside. The Dynamic Environment that Favors Intestinal Homeostasis.}, journal = {Frontiers in immunology}, volume = {4}, number = {}, pages = {323}, pmid = {24130559}, issn = {1664-3224}, abstract = {An organism is defined as "an individual living thing capable of responding to stimuli, growing, reproducing, and maintaining homeostasis." Early during evolution multicellular organisms explored the advantages of a symbiotic life. Mammals harbor a complex aggregate of microorganisms (called microbiota) that includes bacteria, fungi, and archaea. Some of these bacteria have already defined beneficial roles for the human host that include the ability to break down nutrients that could not otherwise be digested, preventing the growth of harmful species, as well as the ability to produce vitamins or hormones. It is intuitive that along the evolutionary path several mechanisms favored bacteria that provided advantages to the host which, in return, avoided launching an aggressive immunological response against them. The intestinal immunological response does not ignore the lumenal content, on the contrary, immune surveillance is favored by continuous antigen sampling. Some intestinal epithelial cells (ECs) are crucial during the sampling process, others actively participate in the defense mechanism. In essence the epithelium acts as a traffic light, communicating to the inside world whether conditions are safe or dangerous, and thus influencing immunological response. In this review we will discuss the dynamic factors that act on the intestinal ECs and how they directly or indirectly influence immune cells during states of health and disease.}, } @article {pmid24128845, year = {2013}, author = {Bae, J and Jeong, S and Lee, JY and Lee, HJ and Choi, BH and Kim, JE and Choi, I and Chun, T}, title = {Molecular cloning and expression analysis of pig CD138.}, journal = {Research in veterinary science}, volume = {95}, number = {3}, pages = {1021-1025}, doi = {10.1016/j.rvsc.2013.09.010}, pmid = {24128845}, issn = {1532-2661}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Western/veterinary ; Cloning, Molecular ; Flow Cytometry/veterinary ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment/veterinary ; Swine/genetics ; Syndecan-1/*genetics/physiology ; Tissue Distribution ; }, abstract = {CD138 (syndecan-1) interacts with various components of the extracellular matrix and associates with the actin cytoskeleton. In this study, we cloned pig CD138 cDNA and determined its complete cDNA sequence. Pig CD138 cDNA contained an open reading frame (930 bp) encoding 309 amino acids with five well conserved putative glycosaminoglycan attachment sites, a putative cleavage site for matrix metalloproteinases, and conserved motifs involved in signal transduction among mammalian species. Pig CD138 mRNA was detected in various tissues, including lymphoid and non-lymphoid organs, indicating the multicellular functions of CD138 in pigs. Western blot and flow cytometry analyses detected an approximate 35 kDa pig CD138 protein expressed on the cell surface. Further immunohistochemistry analysis revealed that CD138 expression was mainly observed in submucosa and lamina propria of the pig small intestine. Further study will be necessary to define the functional importance of CD138 during specific infectious diseases in pigs.}, } @article {pmid24125648, year = {2013}, author = {Morino, Y and Okada, K and Niikura, M and Honda, M and Satoh, N and Wada, H}, title = {A genome-wide survey of genes encoding transcription factors in the Japanese pearl oyster, Pinctada fucata: I. homeobox genes.}, journal = {Zoological science}, volume = {30}, number = {10}, pages = {851-857}, doi = {10.2108/zsj.30.851}, pmid = {24125648}, issn = {0289-0003}, mesh = {Animals ; Gene Expression Regulation/physiology ; Genes, Homeobox/*genetics ; *Genome ; Phylogeny ; Pinctada/*genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Homeobox genes are involved in various aspects of the development of multicellular animals, including anterior-posterior patterning of the body plan. We performed a genomic survey of homeobox genes in the Japanese pearl oyster, Pinctada fucata, and annotated 92 homeobox-containing genes and five homeobox-less Pax genes. This species possesses 10 or 11 Hox genes. We annotated another homeobox genes that cover 77 out of the 111 gene families identified in the amphioxus genome. Investigation of these repertoires of homeobox genes will shed new light on the comparatively less well-understood lophotrochozoan development.}, } @article {pmid24120560, year = {2013}, author = {Smith, ME and Gryganskyi, A and Bonito, G and Nouhra, E and Moreno-Arroyo, B and Benny, G}, title = {Phylogenetic analysis of the genus Modicella reveals an independent evolutionary origin of sporocarp-forming fungi in the Mortierellales.}, journal = {Fungal genetics and biology : FG & B}, volume = {61}, number = {}, pages = {61-68}, doi = {10.1016/j.fgb.2013.10.001}, pmid = {24120560}, issn = {1096-0937}, mesh = {Cluster Analysis ; DNA, Fungal/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Fungi/*classification/*genetics ; Molecular Sequence Data ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Most studies of tissue differentiation and development have focused on animals and plants but many fungi form multi-cellular aggregations of spore-bearing tissue known as fruiting bodies or sporocarps. The ability to form sporocarps has arisen independently in several different evolutionary lineages of fungi. Evolutionary relationships of most sporocarp-forming fungi are well known, but the enigmatic zygomycete genus Modicella contains two species of sporocarp-forming fungi for which the phylogenetic affinities have not been explored based on molecular data. Species of Modicella have an uncertain trophic mode and have alternatively been considered members of the order Endogonales (which contains documented species of sporocarp-forming fungi) or the order Mortierellales (which contains no previously documented species of sporocarp-forming fungi). In this study we perform phylogenetic analyses based on ribosomal DNA of Modicella malleola from the Northern Hemisphere and Modicella reniformis from the Southern Hemisphere to determine the evolutionary affinities of the genus Modicella. Our analyses indicate that Modicella is a monophyletic genus of sporocarp-forming fungi nested within the Mortierellales, a group of microfungi with no previously documented sporocarp-forming species. Because Modicella is distantly related to all other known sporocarp-forming fungi, we infer that this lineage has independently evolved the ability form sporocarps. We conclude that the genus Modicella should be a high priority for comparative genomics studies to further elucidate the process of sporocarp formation in fungi.}, } @article {pmid24118120, year = {2013}, author = {Vijendravarma, RK and Kawecki, TJ}, title = {Epistasis and maternal effects in experimental adaptation to chronic nutritional stress in Drosophila.}, journal = {Journal of evolutionary biology}, volume = {26}, number = {12}, pages = {2566-2580}, doi = {10.1111/jeb.12248}, pmid = {24118120}, issn = {1420-9101}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Drosophila/genetics/*physiology ; *Epistasis, Genetic ; Female ; *Nutritional Status ; *Stress, Physiological ; }, abstract = {Based on ecological and metabolic arguments, some authors predict that adaptation to novel, harsh environments should involve alleles showing negative (diminishing return) epistasis and/or that it should be mediated in part by evolution of maternal effects. Although the first prediction has been supported in microbes, there has been little experimental support for either prediction in multicellular eukaryotes. Here we use a line-cross design to study the genetic architecture of adaptation to chronic larval malnutrition in a population of Drosophila melanogaster that evolved on an extremely nutrient-poor larval food for 84 generations. We assayed three fitness-related traits (developmental rate, adult female weight and egg-to-adult viability) under the malnutrition conditions in 14 crosses between this selected population and a nonadapted control population originally derived from the same base population. All traits showed a pattern of negative epistasis between alleles improving performance under malnutrition. Furthermore, evolutionary changes in maternal traits accounted for half of the 68% increase in viability and for the whole of 8% reduction in adult female body weight in the selected population (relative to unselected controls). These results thus support both of the above predictions and point to the importance of nonadditive effects in adaptive microevolution.}, } @article {pmid24109602, year = {2014}, author = {Mukherjee, K and Korithoski, B and Kolaczkowski, B}, title = {Ancient origins of vertebrate-specific innate antiviral immunity.}, journal = {Molecular biology and evolution}, volume = {31}, number = {1}, pages = {140-153}, pmid = {24109602}, issn = {1537-1719}, support = {R21 AI101571/AI/NIAID NIH HHS/United States ; AI101571-02/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; *Immunity, Innate ; Molecular Sequence Data ; Open Reading Frames ; *Phylogeny ; Protein Conformation ; RNA Helicases/genetics/immunology ; RNA, Viral/genetics ; RNA-Binding Proteins/genetics/metabolism ; Receptors, Pattern Recognition/genetics/immunology ; Sequence Alignment ; Vertebrates/classification/*immunology/*virology ; }, abstract = {Animals deploy various molecular sensors to detect pathogen infections. RIG-like receptor (RLR) proteins identify viral RNAs and initiate innate immune responses. The three human RLRs recognize different types of RNA molecules and protect against different viral pathogens. The RLR protein family is widely thought to have originated shortly before the emergence of vertebrates and rapidly diversified through a complex process of domain grafting. Contrary to these findings, here we show that full-length RLRs and their downstream signaling molecules were present in the earliest animals, suggesting that the RLR-based immune system arose with the emergence of multicellularity. Functional differentiation of RLRs occurred early in animal evolution via simple gene duplication followed by modifications of the RNA-binding pocket, many of which may have been adaptively driven. Functional analysis of human and ancestral RLRs revealed that the ancestral RLR displayed RIG-1-like RNA-binding. MDA5-like binding arose through changes in the RNA-binding pocket following the duplication of the ancestral RLR, which may have occurred either early in Bilateria or later, after deuterostomes split from protostomes. The sensitivity and specificity with which RLRs bind different RNA structures has repeatedly adapted throughout mammalian evolution, suggesting a long-term evolutionary arms race with viral RNA or other molecules.}, } @article {pmid24106029, year = {2013}, author = {Rehorek, SJ and Grand-Pierre, AE and Cummings, JR and Jewell, B and Constantine, J and Hillenius, WJ}, title = {A re-examination and re-evaluation of salamander orbital glands.}, journal = {Anatomical record (Hoboken, N.J. : 2007)}, volume = {296}, number = {11}, pages = {1789-1796}, doi = {10.1002/ar.22782}, pmid = {24106029}, issn = {1932-8494}, mesh = {Animals ; Biological Evolution ; Environment ; Female ; Harderian Gland/*anatomy & histology ; Male ; Nasolabial Fold/*anatomy & histology ; Nasolacrimal Duct/*anatomy & histology ; North America ; Orbit/*anatomy & histology ; Phylogeny ; Terminology as Topic ; Urodela/*anatomy & histology ; }, abstract = {The amphibian integument contains numerous multicellular glands. Although two of these, the nasolabial and orbital glands and the associated nasolacrimal duct (NLD), have historically received considerable attention, interpretation of the original observations can be problematic in the context of current literature. Salamanders, in particular, are frequently regarded as at least indicative of aspects of the morphology of the common ancestor to all extant tetrapods; hence, an understanding of these glands in salamanders might prove to be informative about their evolution. For this study, the orbitonasal region of salamanders from three families was histologically examined. Three themes emerged: (1) examination of the effect of phylogeny on the nasolabial gland and NLD revealed a combination of features that may be unique to plethodontid salamanders, and may be correlated to their nose-tapping behavior by which substances are moved into the vomeronasal organ; (2) ecology appears to impact the relative development of the orbital glands, but not necessarily the nasolabial gland, with smaller glands being present in the aquatic species; (3) the nomenclature of the salamander orbital gland remains problematic, especially in light of comparative studies, as several alternate possibilities are viable. From this nomenclatural conundrum, however, it could be concluded that there may be a global pattern in the location of tetrapod orbital gland development. Molecular questions in terms of ontogeny and genetic homology affect the nature of the debate on orbital gland nomenclature. These observations suggest that rather than reflecting an ancestral condition, salamanders may instead represent a case of specialized, convergent evolution.}, } @article {pmid24098140, year = {2013}, author = {Frédéric, MY and Lundin, VF and Whiteside, MD and Cueva, JG and Tu, DK and Kang, SY and Singh, H and Baillie, DL and Hutter, H and Goodman, MB and Brinkman, FS and Leroux, MR}, title = {Identification of 526 conserved metazoan genetic innovations exposes a new role for cofactor E-like in neuronal microtubule homeostasis.}, journal = {PLoS genetics}, volume = {9}, number = {10}, pages = {e1003804}, pmid = {24098140}, issn = {1553-7404}, support = {R01 NS047715/NS/NINDS NIH HHS/United States ; R01NS047715/NS/NINDS NIH HHS/United States ; BMB173007/CAPMC/CIHR/Canada ; }, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans/genetics/metabolism ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Homeostasis ; Humans ; Metabolic Networks and Pathways/genetics ; Microtubule-Associated Proteins/*genetics/metabolism ; Microtubules/*genetics/metabolism ; Neurons/*metabolism ; Phylogeny ; Placozoa/genetics ; }, abstract = {The evolution of metazoans from their choanoflagellate-like unicellular ancestor coincided with the acquisition of novel biological functions to support a multicellular lifestyle, and eventually, the unique cellular and physiological demands of differentiated cell types such as those forming the nervous, muscle and immune systems. In an effort to understand the molecular underpinnings of such metazoan innovations, we carried out a comparative genomics analysis for genes found exclusively in, and widely conserved across, metazoans. Using this approach, we identified a set of 526 core metazoan-specific genes (the 'metazoanome'), approximately 10% of which are largely uncharacterized, 16% of which are associated with known human disease, and 66% of which are conserved in Trichoplax adhaerens, a basal metazoan lacking neurons and other specialized cell types. Global analyses of previously-characterized core metazoan genes suggest a prevalent property, namely that they act as partially redundant modifiers of ancient eukaryotic pathways. Our data also highlights the importance of exaptation of pre-existing genetic tools during metazoan evolution. Expression studies in C. elegans revealed that many metazoan-specific genes, including tubulin folding cofactor E-like (TBCEL/coel-1), are expressed in neurons. We used C. elegans COEL-1 as a representative to experimentally validate the metazoan-specific character of our dataset. We show that coel-1 disruption results in developmental hypersensitivity to the microtubule drug paclitaxel/taxol, and that overexpression of coel-1 has broad effects during embryonic development and perturbs specialized microtubules in the touch receptor neurons (TRNs). In addition, coel-1 influences the migration, neurite outgrowth and mechanosensory function of the TRNs, and functionally interacts with components of the tubulin acetylation/deacetylation pathway. Together, our findings unveil a conserved molecular toolbox fundamental to metazoan biology that contains a number of neuronally expressed and disease-related genes, and reveal a key role for TBCEL/coel-1 in regulating microtubule function during metazoan development and neuronal differentiation.}, } @article {pmid24085781, year = {2013}, author = {Kozubowski, L and Yadav, V and Chatterjee, G and Sridhar, S and Yamaguchi, M and Kawamoto, S and Bose, I and Heitman, J and Sanyal, K}, title = {Ordered kinetochore assembly in the human-pathogenic basidiomycetous yeast Cryptococcus neoformans.}, journal = {mBio}, volume = {4}, number = {5}, pages = {e00614-13}, pmid = {24085781}, issn = {2150-7511}, support = {R37AI39115-15/AI/NIAID NIH HHS/United States ; R01 AI039115/AI/NIAID NIH HHS/United States ; R01 AI050113/AI/NIAID NIH HHS/United States ; R37 AI039115/AI/NIAID NIH HHS/United States ; R01AI50113-10/AI/NIAID NIH HHS/United States ; }, mesh = {Chromosomes, Fungal/genetics/metabolism ; Cryptococcosis/*microbiology ; Cryptococcus neoformans/*cytology/genetics/*metabolism ; Fungal Proteins/genetics/metabolism ; Humans ; Kinetochores/*metabolism ; Mitosis ; }, abstract = {UNLABELLED: Kinetochores facilitate interaction between chromosomes and the spindle apparatus. The formation of a metazoan trilayered kinetochore is an ordered event in which inner, middle, and outer layers assemble during disassembly of the nuclear envelope during mitosis. The existence of a similar strong correlation between kinetochore assembly and nuclear envelope breakdown in unicellular eukaryotes is unclear. Studies in the hemiascomycetous budding yeasts Saccharomyces cerevisiae and Candida albicans suggest that an ordered kinetochore assembly may not be evolutionarily conserved. Here, we utilized high-resolution time-lapse microscopy to analyze the localization patterns of a series of putative kinetochore proteins in the basidiomycetous budding yeast Cryptococcus neoformans, a human pathogen. Strikingly, similar to most metazoa but atypical of yeasts, the centromeres are not clustered but positioned adjacent to the nuclear envelope in premitotic C. neoformans cells. The centromeres gradually coalesce to a single cluster as cells progress toward mitosis. The mitotic clustering of centromeres seems to be dependent on the integrity of the mitotic spindle. To study the dynamics of the nuclear envelope, we followed the localization of two marker proteins, Ndc1 and Nup107. Fluorescence microscopy of the nuclear envelope and components of the kinetochore, along with ultrastructure analysis by transmission electron microscopy, reveal that in C. neoformans, the kinetochore assembles in an ordered manner prior to mitosis in concert with a partial opening of the nuclear envelope. Taken together, the results of this study demonstrate that kinetochore dynamics in C. neoformans is reminiscent of that of metazoans and shed new light on the evolution of mitosis in eukaryotes.

IMPORTANCE: Successful propagation of genetic material in progeny is essential for the survival of any organism. A proper kinetochore-microtubule interaction is crucial for high-fidelity chromosome segregation. An error in this process can lead to loss or gain of chromosomes, a common feature of most solid cancers. Several proteins assemble on centromere DNA to form a kinetochore. However, significant differences in the process of kinetochore assembly exist between unicellular yeasts and multicellular metaozoa. Here, we examined the key events that lead to formation of a proper kinetochore in a basidiomycetous budding yeast, Cryptococcus neoformans. We found that, during the progression of the cell cycle, nonclustered centromeres gradually clustered and kinetochores assembled in an ordered manner concomitant with partial opening of the nuclear envelope in this organism. These events have higher similarity to mitotic events of metazoans than to those previously described in other yeasts.}, } @article {pmid24085520, year = {2013}, author = {Khokhlov, AN}, title = {Impairment of regeneration in aging: appropriateness or stochastics?.}, journal = {Biogerontology}, volume = {14}, number = {6}, pages = {703-708}, doi = {10.1007/s10522-013-9468-x}, pmid = {24085520}, issn = {1573-6768}, mesh = {Aging/*pathology ; Animals ; Cell Proliferation ; Cellular Senescence ; Humans ; *Models, Biological ; *Regeneration ; Stochastic Processes ; }, abstract = {There is a viewpoint that suppression of the proliferative capacity of cells and impairment of the regeneration of tissues and organs in aging are a consequence of specially arisen during evolution mechanisms that reduce the risk of malignant transformation and, thus, protect against cancer. We believe that the restriction of cell proliferation in an aging multicellular organism is not a consequence of implementing a special program of aging. Apparently, such a program does not exist at all and aging is only a "byproduct" of the program of development, implementation of which in higher organisms suggests the need for the emergence of cell populations with very low or even zero proliferative activity, which determines the limited capacity of relevant organs and tissues to regenerate. At the same time, it is the presence of highly differentiated cell populations, barely able or completely unable to reproduce (neurons, cardiomyocytes, hepatocytes), that ensures the normal functioning of the higher animals and humans. Apparently, the impairment of regulatory processes, realized at the neurohumoral level, still plays the main role in the mechanisms of aging of multicellular organisms, not just the accumulation of macromolecular defects in individual cells. It seems that the quality of the cells themselves does not worsen with age as much as reliability of the organism control over cells, organs and tissues, which leads to an increase in the probability of death.}, } @article {pmid24081281, year = {2013}, author = {Nogueira, A and Ottra, JH and Guimarães, E and Machado, SR and Lohmann, LG}, title = {Trichome structure and evolution in Neotropical lianas.}, journal = {Annals of botany}, volume = {112}, number = {7}, pages = {1331-1350}, pmid = {24081281}, issn = {1095-8290}, mesh = {Bignoniaceae/*anatomy & histology/ultrastructure ; *Biological Evolution ; Likelihood Functions ; Phylogeny ; Trichomes/*anatomy & histology/ultrastructure ; *Tropical Climate ; }, abstract = {BACKGROUND AND AIMS: Trichomes are epidermal outgrowths generally associated with protection against herbivores and/or desiccation that are widely distributed from ferns to angiosperms. Patterns of topological variation and morphological evolution of trichomes are still scarce in the literature, preventing valid comparisons across taxa. This study integrates detailed morphoanatomical data and the evolutionary history of the tribe Bignonieae (Bignoniaceae) in order to gain a better understanding of current diversity and evolution of trichome types.

METHODS: Two sampling schemes were used to characterize trichome types: (1) macromorphological characterization of all 105 species currently included in Bignonieae; and (2) micromorphological characterization of 16 selected species. Individual trichome morphotypes were coded as binary in each vegetative plant part, and trichome density and size were coded as multistate. Ancestral character state reconstructions were conducted using maximum likelihood (ML) assumptions.

KEY RESULTS: Two main functional trichome categories were found: non-glandular and glandular. In glandular trichomes, three morphotypes were recognized: peltate (Pg), stipitate (Sg) and patelliform/cupular (P/Cg) trichomes. Non-glandular trichomes were uniseriate, uni- or multicellular and simple or branched. Pg and P/Cg trichomes were multicellular and non-vascularized with three clearly distinct cell layers. Sg trichomes were multicellular, uniseriate and long-stalked. ML ancestral character state reconstructions suggested that the most recent common ancestor (MRCA) of Bignonieae probably had non-glandular, Pg and P/Cg trichomes, with each trichome type presenting alternative histories of appearance on the different plant parts. For example, the MRCA of Bignonieae probably had non-glandular trichomes on the stems, prophylls, petiole, petiolule and leaflet veins while P/Cg trichomes were restricted to leaflet blades. Sg trichomes were not present in the MRCA of Bignonieae independently of the position of these trichomes. These trichomes had at least eight independent origins in tribe.

CONCLUSIONS: The patterns of trichome evolution indicate that most morphotypes are probably homologous in Bignonieae and could be treated under the same name based on its morphological similarity and common evolutionary history, in spite of the plethora of names that have been previously designated in the literature. The trichome descriptions presented here will facilitate comparisons across taxa, allowing inferences on the relationsthips between trichome variants and future studies about their functional properties.}, } @article {pmid24080887, year = {2013}, author = {Gómez-Lus, ML and Corcuera, MT and Gómez-Lus, R and Sánchez-Serrano, C and Gómez-Aguado, F and Alonso, MJ and Prieto, J}, title = {[Structural dynamics of Legionella pneumophila and Legionella bozemanii colony/biofilm].}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {26}, number = {3}, pages = {214-219}, pmid = {24080887}, issn = {1988-9518}, mesh = {Biofilms/*growth & development ; Culture Media ; Humans ; Image Processing, Computer-Assisted ; Legionella/*growth & development/physiology ; Legionella pneumophila/*growth & development/physiology ; Legionnaires' Disease/microbiology ; Microscopy, Electron, Transmission ; Paraffin Embedding ; Plastic Embedding ; Species Specificity ; }, abstract = {OBJECTIVES: The genus Legionella includes very pleomorphic species responsible for disease outbreaks in humans. The appearance of such has great importance to develop artificial biofilms in aquatic ecosystems. The aim of this work was to study the dynamics of growth and evolution of the internal structure of colonies of representative species of the genus as static biofilm model.

METHODS: Isolated colonies of Legionella pneumophila and Legionella bozemanii grown in specific media for three and fifteen days were processed for histological methods and embedded in paraffin and epoxy resin for analysis by light microscopy, electron microscopy and image analysis. RESULTS. In colonies of both species were observed and defined specific architectural patterns, based on stratification and evolve over time. The strata differ in the amount of extracellular matrix, the morphology and population density and the proportion of dead cells. The internal structure of three days colonies showed large differences between L. pneumophila (two layers) and L. bozemanii (four layers). However, in the fifteen days colonies of both species evolved towards a common unique pattern formed by three layers. In both species the growth was also found within the culture medium, although this phenomenon was more intense in L. bozemanii with unique, central and larger invasions.

CONCLUSIONS: Our results demonstrate that Legionella colonies on solid culture media are a good model of static biofilm with a complex structural dynamics characterized by the presence of morphological and functional subpopulations. We bring here an histological approach model, allowing, in further research, detailed studies in evolutionary adaptations in multicellular communities to adverse media and to antimicrobials in Legionella species of clinical interest.}, } @article {pmid24080405, year = {2014}, author = {Murcha, MW and Wang, Y and Narsai, R and Whelan, J}, title = {The plant mitochondrial protein import apparatus - the differences make it interesting.}, journal = {Biochimica et biophysica acta}, volume = {1840}, number = {4}, pages = {1233-1245}, doi = {10.1016/j.bbagen.2013.09.026}, pmid = {24080405}, issn = {0006-3002}, mesh = {Membrane Transport Proteins/*physiology ; Mitochondria/genetics/*metabolism ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Plant Proteins/genetics/*metabolism ; Plants/*metabolism/ultrastructure ; Protein Transport/physiology ; Saccharomyces cerevisiae/*metabolism/ultrastructure ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {BACKGROUND: Mitochondria play essential roles in the life and death of almost all eukaryotic cells, ranging from single-celled to multi-cellular organisms that display tissue and developmental differentiation. As mitochondria only arose once in evolution, much can be learned from studying single celled model systems such as yeast and applying this knowledge to other organisms. However, two billion years of evolution have also resulted in substantial divergence in mitochondrial function between eukaryotic organisms.

SCOPE OF REVIEW: Here we review our current understanding of the mechanisms of mitochondrial protein import between plants and yeast (Saccharomyces cerevisiae) and identify a high level of conservation for the essential subunits of plant mitochondrial import apparatus. Furthermore, we investigate examples whereby divergence and acquisition of functions have arisen and highlight the emerging examples of interactions between the import apparatus and components of the respiratory chain.

MAJOR CONCLUSIONS: After more than three decades of research into the components and mechanisms of mitochondrial protein import of plants and yeast, the differences between these systems are examined. Specifically, expansions of the small gene families that encode the mitochondrial protein import apparatus in plants are detailed, and their essential role in seed viability is revealed.

GENERAL SIGNIFICANCE: These findings point to the essential role of the inner mitochondrial protein translocases in Arabidopsis, establishing their necessity for seed viability and the crucial role of mitochondrial biogenesis during germination. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.}, } @article {pmid24068653, year = {2013}, author = {de Paula, WB and Agip, AN and Missirlis, F and Ashworth, R and Vizcay-Barrena, G and Lucas, CH and Allen, JF}, title = {Female and male gamete mitochondria are distinct and complementary in transcription, structure, and genome function.}, journal = {Genome biology and evolution}, volume = {5}, number = {10}, pages = {1969-1977}, pmid = {24068653}, issn = {1759-6653}, mesh = {Adenosine Triphosphate/biosynthesis ; Aging/genetics ; Animals ; *Biological Evolution ; DNA, Mitochondrial/*genetics ; Electron Transport/genetics ; Female ; Free Radicals/metabolism ; Germ Cells/metabolism ; Male ; Mitochondria/genetics/metabolism ; Oocytes/*metabolism ; Oxygen/metabolism ; Spermatozoa/*metabolism ; *Transcription, Genetic ; Zebrafish/metabolism ; }, abstract = {Respiratory electron transport in mitochondria is coupled to ATP synthesis while generating mutagenic oxygen free radicals. Mitochondrial DNA mutation then accumulates with age, and may set a limit to the lifespan of individual, multicellular organisms. Why is this mutation not inherited? Here we demonstrate that female gametes-oocytes-have unusually small and simple mitochondria that are suppressed for DNA transcription, electron transport, and free radical production. By contrast, male gametes-sperm-and somatic cells of both sexes transcribe mitochondrial genes for respiratory electron carriers and produce oxygen free radicals. This germ-line division between mitochondria of sperm and egg is observed in both the vinegar fruitfly and the zebrafish-species spanning a major evolutionary divide within the animal kingdom. We interpret these findings as an evidence that oocyte mitochondria serve primarily as genetic templates, giving rise, irreversibly and in each new generation, to the familiar energy-transducing mitochondria of somatic cells and male gametes. Suppressed mitochondrial metabolism in the female germ line may therefore constitute a mechanism for increasing the fidelity of mitochondrial DNA inheritance.}, } @article {pmid24067914, year = {2013}, author = {Weis, WI and Nelson, WJ and Dickinson, DJ}, title = {Evolution and cell physiology. 3. Using Dictyostelium discoideum to investigate mechanisms of epithelial polarity.}, journal = {American journal of physiology. Cell physiology}, volume = {305}, number = {11}, pages = {C1091-5}, pmid = {24067914}, issn = {1522-1563}, support = {GM-035527/GM/NIGMS NIH HHS/United States ; GM-56169/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Physiological Phenomena/physiology ; Cell Polarity/*physiology ; Dictyostelium/cytology/*physiology ; Epithelial Cells/*physiology ; *Evolution, Molecular ; Humans ; }, abstract = {In Metazoa, a polarized epithelium forms a single-cell-layered barrier that separates the outside from the inside of the organism. In tubular epithelia, the apical side of the cell is constricted relative to the basal side, forming a wedge-shaped cell that can pack into a tube. Apical constriction is mediated by actomyosin activity. In higher animals, apical actomyosin is connected between cells by specialized cell-cell junctions that contain a classical cadherin, the Wnt signaling protein β-catenin, and the actin-binding protein α-catenin. The molecular mechanisms that lead to selective accumulation of myosin at the apical surface of cells are poorly understood. We found that the nonmetazoan Dictyostelium discoideum forms a polarized epithelium that surrounds the stalk tube at the tip of the multicellular fruiting body. Although D. discoideum lacks a cadherin homolog, it expresses homologs of β- and α-catenin. Both catenins are essential for formation of the tip epithelium, polarized protein secretion, and proper multicellular morphogenesis. Myosin localizes apically in tip epithelial cells, and it appears that constriction of this epithelial tube is required for proper morphogenesis. Localization of myosin II is controlled by the protein IQGAP1 and its binding partners cortexillins I and II, which function downstream of α- and β-catenin to exclude myosin from the basolateral cortex and promote apical accumulation of myosin. These studies show that the function of catenins in cell polarity predates the evolution of Wnt signaling and classical cadherins, and that apical localization of myosin is a morphogenetic mechanism conserved from nonmetazoans to vertebrates.}, } @article {pmid24066281, year = {2013}, author = {Bozzaro, S and Buracco, S and Peracino, B}, title = {Iron metabolism and resistance to infection by invasive bacteria in the social amoeba Dictyostelium discoideum.}, journal = {Frontiers in cellular and infection microbiology}, volume = {3}, number = {}, pages = {50}, pmid = {24066281}, issn = {2235-2988}, mesh = {Cation Transport Proteins/metabolism ; Dictyostelium/*metabolism/*microbiology ; Homeostasis ; Iron/*metabolism ; Legionella/*metabolism ; Mycobacterium/*metabolism ; }, abstract = {Dictyostelium cells are forest soil amoebae, which feed on bacteria and proliferate as solitary cells until bacteria are consumed. Starvation triggers a change in life style, forcing cells to gather into aggregates to form multicellular organisms capable of cell differentiation and morphogenesis. As a soil amoeba and a phagocyte that grazes on bacteria as the obligate source of food, Dictyostelium could be a natural host of pathogenic bacteria. Indeed, many pathogens that occasionally infect humans are hosted for most of their time in protozoa or free-living amoebae, where evolution of their virulence traits occurs. Due to these features and its amenability to genetic manipulation, Dictyostelium has become a valuable model organism for studying strategies of both the host to resist infection and the pathogen to escape the defense mechanisms. Similarly to higher eukaryotes, iron homeostasis is crucial for Dictyostelium resistance to invasive bacteria. Iron is essential for Dictyostelium, as both iron deficiency or overload inhibit cell growth. The Dictyostelium genome shares with mammals many genes regulating iron homeostasis. Iron transporters of the Nramp (Slc11A) family are represented with two genes, encoding Nramp1 and Nramp2. Like the mammalian ortholog, Nramp1 is recruited to phagosomes and macropinosomes, whereas Nramp2 is a membrane protein of the contractile vacuole network, which regulates osmolarity. Nramp1 and Nramp2 localization in distinct compartments suggests that both proteins synergistically regulate iron homeostasis. Rather than by absorption via membrane transporters, iron is likely gained by degradation of ingested bacteria and efflux via Nramp1 from phagosomes to the cytosol. Nramp gene disruption increases Dictyostelium sensitivity to infection, enhancing intracellular growth of Legionella or Mycobacteria. Generation of mutants in other "iron genes" will help identify genes essential for iron homeostasis and resistance to pathogens.}, } @article {pmid24059699, year = {2013}, author = {Hein, M and Graver, S}, title = {Tumor cell response to bevacizumab single agent therapy in vitro.}, journal = {Cancer cell international}, volume = {13}, number = {1}, pages = {94}, pmid = {24059699}, issn = {1475-2867}, abstract = {BACKGROUND: Angiogenesis represents a highly multi-factorial and multi-cellular complex (patho-) physiologic event involving endothelial cells, tumor cells in malignant conditions, as well as bone marrow derived cells and stromal cells. One main driver is vascular endothelial growth factor (VEGFA), which is known to interact with endothelial cells as a survival and mitogenic signal. The role of VEGFA on tumor cells and /or tumor stromal cell interaction is less clear. Condition specific (e.g. hypoxia) or tumor specific expression of VEGFA, VEGF receptors and co-receptors on tumor cells has been reported, in addition to the expression on the endothelium. This suggests a potential paracrine/autocrine loop that could affect changes specific to tumor cells.

METHODS: We used the monoclonal antibody against VEGFA, bevacizumab, in various in vitro experiments using cell lines derived from different tumor entities (non small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer (BC) and renal cell carcinoma (RCC)) in order to determine if potential VEGFA signaling could be blocked in tumor cells. The experiments were done under hypoxia, a major inducer of VEGFA and angiogenesis, in an attempt to mimic the physiological tumor condition. Known VEGFA induced endothelial biological responses such as proliferation, migration, survival and gene expression changes were evaluated.

RESULTS: Our study was able to demonstrate expression of VEGF receptors on tumor cells as well as hypoxia regulated angiogenic gene expression. In addition, there was a cell line specific effect in tumor cells by VEGFA blockade with bevacizumab in terms of proliferation; however overall, there was a limited measurable consequence of bevacizumab therapy detected by migration and survival.

CONCLUSION: The present study showed in a variety of in vitro experiments with several tumor cell lines from different tumor origins, that by blocking VEGFA with bevacizumab, there was a limited autocrine or cell-autonomous function of VEGFA signaling in tumor cells, when evaluating VEGFA induced downstream outputs known in endothelial cells.}, } @article {pmid24048930, year = {2014}, author = {Wanninger, A and Wollesen, T}, title = {Methods in brain development of molluscs.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1082}, number = {}, pages = {117-125}, doi = {10.1007/978-1-62703-655-9_8}, pmid = {24048930}, issn = {1940-6029}, mesh = {Animals ; Brain/cytology/embryology/*growth & development ; Immunohistochemistry/instrumentation/*methods ; *Mollusca ; Vibration ; }, abstract = {Representatives of the phylum Mollusca have long been important models in neurobiological research. Recently, the routine application of immunocytochemistry in combination with confocal laser scanning microscopy has allowed fast generation of highly detailed reconstructions of neural structures of even the smallest multicellular animals, including early developmental stages. As a consequence, large-scale comparative analyses of neurogenesis-an important prerequisite for inferences concerning the evolution of animal nervous systems-are now possible in a reasonable amount of time. Herein, we describe immunocytochemical staining protocols for both whole-mount preparations of developmental stages-usually 70-300 μm in size-as well as for vibratome sections of complex brains. Although our procedures have been optimized for marine molluscs, they may easily be adapted for other (marine) organisms by the creative neurobiologist.}, } @article {pmid24043797, year = {2013}, author = {Sebé-Pedrós, A and Ariza-Cosano, A and Weirauch, MT and Leininger, S and Yang, A and Torruella, G and Adamski, M and Adamska, M and Hughes, TR and Gómez-Skarmeta, JL and Ruiz-Trillo, I}, title = {Early evolution of the T-box transcription factor family.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {40}, pages = {16050-16055}, pmid = {24043797}, issn = {1091-6490}, support = {206883/ERC_/European Research Council/International ; MOP-111007/CAPMC/CIHR/Canada ; }, mesh = {Animals ; *Evolution, Molecular ; Fetal Proteins/*genetics ; Histocytochemistry ; Mesomycetozoea/*genetics ; Microarray Analysis ; Multigene Family/*genetics ; *Phenotype ; *Phylogeny ; Protein Binding ; Real-Time Polymerase Chain Reaction ; Species Specificity ; T-Box Domain Proteins/*genetics ; Xenopus/*genetics ; }, abstract = {Developmental transcription factors are key players in animal multicellularity, being members of the T-box family that are among the most important. Until recently, T-box transcription factors were thought to be exclusively present in metazoans. Here, we report the presence of T-box genes in several nonmetazoan lineages, including ichthyosporeans, filastereans, and fungi. Our data confirm that Brachyury is the most ancient member of the T-box family and establish that the T-box family diversified at the onset of Metazoa. Moreover, we demonstrate functional conservation of a homolog of Brachyury of the protist Capsaspora owczarzaki in Xenopus laevis. By comparing the molecular phenotype of C. owczarzaki Brachyury with that of homologs of early branching metazoans, we define a clear difference between unicellular holozoan and metazoan Brachyury homologs, suggesting that the specificity of Brachyury emerged at the origin of Metazoa. Experimental determination of the binding preferences of the C. owczarzaki Brachyury results in a similar motif to that of metazoan Brachyury and other T-box classes. This finding suggests that functional specificity between different T-box classes is likely achieved by interaction with alternative cofactors, as opposed to differences in binding specificity.}, } @article {pmid24037739, year = {2013}, author = {Huang, J}, title = {Horizontal gene transfer in eukaryotes: the weak-link model.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {10}, pages = {868-875}, pmid = {24037739}, issn = {1521-1878}, mesh = {Animals ; Eukaryota/*genetics ; Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genes, Bacterial ; Mitochondria/genetics ; *Models, Genetic ; Phylogeny ; Plastids/genetics ; Symbiosis/genetics ; }, abstract = {The significance of horizontal gene transfer (HGT) in eukaryotic evolution remains controversial. Although many eukaryotic genes are of bacterial origin, they are often interpreted as being derived from mitochondria or plastids. Because of their fixed gene pool and gene loss, however, mitochondria and plastids alone cannot adequately explain the presence of all, or even the majority, of bacterial genes in eukaryotes. Available data indicate that no insurmountable barrier to HGT exists, even in complex multicellular eukaryotes. In addition, the discovery of both recent and ancient HGT events in all major eukaryotic groups suggests that HGT has been a regular occurrence throughout the history of eukaryotic evolution. A model of HGT is proposed that suggests both unicellular and early developmental stages as likely entry points for foreign genes into multicellular eukaryotes.}, } @article {pmid24037214, year = {2013}, author = {Lee, YS and Krishnan, A and Zhu, Q and Troyanskaya, OG}, title = {Ontology-aware classification of tissue and cell-type signals in gene expression profiles across platforms and technologies.}, journal = {Bioinformatics (Oxford, England)}, volume = {29}, number = {23}, pages = {3036-3044}, pmid = {24037214}, issn = {1367-4811}, support = {P50 GM071508/GM/NIGMS NIH HHS/United States ; R01 GM071966/GM/NIGMS NIH HHS/United States ; R01 HG005998/HG/NHGRI NIH HHS/United States ; T32 HG003284/HG/NHGRI NIH HHS/United States ; }, mesh = {Bayes Theorem ; Cells/*classification ; Computational Biology/*methods ; *Databases, Factual ; Gene Expression Profiling/*methods ; *High-Throughput Nucleotide Sequencing ; Humans ; Models, Statistical ; Oligonucleotide Array Sequence Analysis/*methods ; Organ Specificity ; }, abstract = {MOTIVATION: Leveraging gene expression data through large-scale integrative analyses for multicellular organisms is challenging because most samples are not fully annotated to their tissue/cell-type of origin. A computational method to classify samples using their entire gene expression profiles is needed. Such a method must be applicable across thousands of independent studies, hundreds of gene expression technologies and hundreds of diverse human tissues and cell-types.

RESULTS: We present Unveiling RNA Sample Annotation (URSA) that leverages the complex tissue/cell-type relationships and simultaneously estimates the probabilities associated with hundreds of tissues/cell-types for any given gene expression profile. URSA provides accurate and intuitive probability values for expression profiles across independent studies and outperforms other methods, irrespective of data preprocessing techniques. Moreover, without re-training, URSA can be used to classify samples from diverse microarray platforms and even from next-generation sequencing technology. Finally, we provide a molecular interpretation for the tissue and cell-type models as the biological basis for URSA's classifications.}, } @article {pmid24032108, year = {2013}, author = {Barteneva, NS and Maltsev, N and Vorobjev, IA}, title = {Microvesicles and intercellular communication in the context of parasitism.}, journal = {Frontiers in cellular and infection microbiology}, volume = {3}, number = {}, pages = {49}, pmid = {24032108}, issn = {2235-2988}, mesh = {Animals ; *Cell Communication ; Exosomes/*metabolism ; *Host-Parasite Interactions ; Humans ; Parasites/*physiology ; }, abstract = {There is a rapidly growing body of evidence that production of microvesicles (MVs) is a universal feature of cellular life. MVs can incorporate microRNA (miRNA), mRNA, mtDNA, DNA and retrotransposons, camouflage viruses/viral components from immune surveillance, and transfer cargo between cells. These properties make MVs an essential player in intercellular communication. Increasing evidence supports the notion that MVs can also act as long-distance vehicles for RNA molecules and participate in metabolic synchronization and reprogramming eukaryotic cells including stem and germinal cells. MV ability to carry on DNA and their general distribution makes them attractive candidates for horizontal gene transfer, particularly between multi-cellular organisms and their parasites; this suggests important implications for the co-evolution of parasites and their hosts. In this review, we provide current understanding of the roles played by MVs in intracellular pathogens and parasitic infections. We also discuss the possible role of MVs in co-infection and host shifting.}, } @article {pmid24030493, year = {2013}, author = {Dejosez, M and Ura, H and Brandt, VL and Zwaka, TP}, title = {Safeguards for cell cooperation in mouse embryogenesis shown by genome-wide cheater screen.}, journal = {Science (New York, N.Y.)}, volume = {341}, number = {6153}, pages = {1511-1514}, doi = {10.1126/science.1241628}, pmid = {24030493}, issn = {1095-9203}, support = {P01 GM81627/GM/NIGMS NIH HHS/United States ; R01 GM077442/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/genetics ; Cell Transdifferentiation/genetics ; Cellular Reprogramming/genetics ; DNA Topoisomerases, Type I/genetics ; Down-Regulation ; Embryonic Development/*genetics ; Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Genome-Wide Association Study ; Induced Pluripotent Stem Cells/metabolism ; Mice ; Mutation ; Receptors, Odorant/genetics ; Tumor Suppressor Protein p53/genetics ; }, abstract = {Ensuring cooperation among formerly autonomous cells has been a central challenge in the evolution of multicellular organisms. One solution is monoclonality, but this option still leaves room for exploitative behavior, as it does not eliminate genetic and epigenetic variability. We therefore hypothesized that embryonic development must be protected by robust regulatory mechanisms that prevent aberrant clones from superseding wild-type cells. Using a genome-wide screen in murine induced pluripotent stem cells, we identified a network of genes (centered on p53, topoisomerase 1, and olfactory receptors) whose down-regulation caused the cells to replace wild-type cells in vitro and in the mouse embryo--without perturbing normal development. These genes thus appear to fulfill an unexpected role in fostering cell cooperation.}, } @article {pmid24026343, year = {2014}, author = {Perera, PI and Ordoñez, CA and Lopez-Lavalle, LA and Dedicova, B}, title = {A milestone in the doubled haploid pathway of cassava: a milestone in the doubled haploid pathway of cassava (Manihot esculenta Crantz): cellular and molecular assessment of anther-derived structures.}, journal = {Protoplasma}, volume = {251}, number = {1}, pages = {233-246}, pmid = {24026343}, issn = {1615-6102}, mesh = {Amplified Fragment Length Polymorphism Analysis ; Cells, Cultured ; Flow Cytometry ; *Haploidy ; Manihot/*cytology/*genetics/growth & development ; Microsatellite Repeats/genetics ; }, abstract = {This study was aimed at inducing androgenesis in cultured anthers of cassava (Manihot esculenta Crantz) to develop a protocol for the production of doubled haploids. Microspore reprogramming was induced in cassava by cold or heat stress of anthers. Since the anthers contain both haploid microspores and diploid somatic cells, it was essential to verify the origin of anther-derived calli. The origin of anther-derived calli was assessed by morphological screening followed by histological analysis and flow cytometry (FCM). Additionally, simple sequence repeat (SSR) and amplified fragmented length polymorphism (AFLP) assays were used for the molecular identification of the microspore-derived calli. The study clearly demonstrated the feasibility of producing microspore-derived calli using heat- or cold-pretreated anthers. Histological studies revealed reprogramming of the developmental pathway of microspores by symmetrical division of the nucleus. Flow cytometry analysis revealed different ploidy level cell types including haploids, which confirmed their origin from the microspores. The SSR and AFLP marker assays independently confirmed the histological and FCM results of a haploid origin of the calli at the DNA level. The presence of multicellular microspores in the in vitro system indicated a switch of developmental program, which constitutes a crucial step in the design of protocols for the regeneration of microspore-derived embryos and plants. This is the first detailed report of calli, embryos, and abnormal shoots originated from the haploid cells in cassava, leading to the development of a protocol for the production of doubled haploid plants in cassava.}, } @article {pmid24021397, year = {2013}, author = {González-Forero, M and Gavrilets, S}, title = {Evolution of manipulated behavior.}, journal = {The American naturalist}, volume = {182}, number = {4}, pages = {439-451}, doi = {10.1086/671932}, pmid = {24021397}, issn = {1537-5323}, mesh = {Animals ; *Biological Evolution ; Helping Behavior ; Insecta/*physiology ; Models, Biological ; *Selection, Genetic ; Social Behavior ; }, abstract = {Many social behaviors are triggered by social partners. For example, cells in a multicellular organism often become soma via extrinsically regulated differentiation, while individuals in a eusocial colony often become helpers via extrinsic caste determination. One explanation for social triggering is that it informs when it is beneficial to express the behavior. Alternatively, social triggering can represent manipulation where social partners partially or completely control the focal individual's behavior. For instance, caste determination in primitively eusocial taxa is typically accomplished via differential feeding or dominance hierarchies, suggesting some manipulation. However, selection would favor resistance if manipulation is detrimental to manipulated parties, and the outcome of the manipulation conflict remains intricate. We analyze the coevolution of manipulation and resistance in a simple but general setting. We show that, despite possible resistance, manipulated behavior can be established under less stringent conditions than spontaneous (i.e., nonmanipulated) behavior because of resistance costs. The existence of this advantage might explain why primitive eusocial behavior tends to be triggered socially and coercively. We provide a simple condition for the advantage of manipulated behavior that may help infer whether a socially triggered behavior is manipulated. We illustrate our analysis with a hypothetical example of maternal manipulation relevant to primitive eusociality.}, } @article {pmid24012879, year = {2013}, author = {Münder, S and Tischer, S and Grundhuber, M and Büchels, N and Bruckmeier, N and Eckert, S and Seefeldt, CA and Prexl, A and Käsbauer, T and Böttger, A}, title = {Notch-signalling is required for head regeneration and tentacle patterning in Hydra.}, journal = {Developmental biology}, volume = {383}, number = {1}, pages = {146-157}, doi = {10.1016/j.ydbio.2013.08.022}, pmid = {24012879}, issn = {1095-564X}, mesh = {Animals ; Bromodeoxyuridine ; DNA Primers/genetics ; Dipeptides ; Extremities/*physiology ; Head/*physiology ; Hydra/*physiology ; In Situ Hybridization ; Microscopy, Confocal ; Receptors, Notch/*metabolism ; Regeneration/*physiology ; Signal Transduction/*physiology ; }, abstract = {Local self-activation and long ranging inhibition provide a mechanism for setting up organising regions as signalling centres for the development of structures in the surrounding tissue. The adult hydra hypostome functions as head organiser. After hydra head removal it is newly formed and complete heads can be regenerated. The molecular components of this organising region involve Wnt-signalling and β-catenin. However, it is not known how correct patterning of hypostome and tentacles are achieved in the hydra head and whether other signals in addition to HyWnt3 are needed for re-establishing the new organiser after head removal. Here we show that Notch-signalling is required for re-establishing the organiser during regeneration and that this is due to its role in restricting tentacle activation. Blocking Notch-signalling leads to the formation of irregular head structures characterised by excess tentacle tissue and aberrant expression of genes that mark the tentacle boundaries. This indicates a role for Notch-signalling in defining the tentacle pattern in the hydra head. Moreover, lateral inhibition by HvNotch and its target HyHes are required for head regeneration and without this the formation of the β-catenin/Wnt dependent head organiser is impaired. Work on prebilaterian model organisms has shown that the Wnt-pathway is important for setting up signalling centres for axial patterning in early multicellular animals. Our data suggest that the integration of Wnt-signalling with Notch-Delta activity was also involved in the evolution of defined body plans in animals.}, } @article {pmid24003001, year = {2013}, author = {Ivancevic, AM and Walsh, AM and Kortschak, RD and Adelson, DL}, title = {Jumping the fine LINE between species: horizontal transfer of transposable elements in animals catalyses genome evolution.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {12}, pages = {1071-1082}, doi = {10.1002/bies.201300072}, pmid = {24003001}, issn = {1521-1878}, mesh = {Animals ; DNA Transposable Elements/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Genome/*genetics ; Retroelements/*genetics ; }, abstract = {Horizontal transfer (HT) is the transmission of genetic material between non-mating species, a phenomenon thought to occur rarely in multicellular eukaryotes. However, many transposable elements (TEs) are not only capable of HT, but have frequently jumped between widely divergent species. Here we review and integrate reported cases of HT in retrotransposons of the BovB family, and DNA transposons, over a broad range of animals spanning all continents. Our conclusions challenge the paradigm that HT in vertebrates is restricted to infective long terminal repeat (LTR) retrotransposons or retroviruses. This raises the possibility that other non-LTR retrotransposons, such as L1 or CR1 elements, believed to be only vertically transmitted, can horizontally transfer between species. Growing evidence indicates that the process of HT is much more general across different TEs and species than previously believed, and that it likely shapes eukaryotic genomes and catalyses genome evolution.}, } @article {pmid23992552, year = {2014}, author = {Ekman, M and Sandh, G and Nenninger, A and Oliveira, P and Stensjö, K}, title = {Cellular and functional specificity among ferritin-like proteins in the multicellular cyanobacterium Nostoc punctiforme.}, journal = {Environmental microbiology}, volume = {16}, number = {3}, pages = {829-844}, doi = {10.1111/1462-2920.12233}, pmid = {23992552}, issn = {1462-2920}, mesh = {Amino Acid Sequence ; Computational Biology ; Ferritins/genetics/*metabolism ; Gene Expression Regulation, Bacterial/drug effects ; Green Fluorescent Proteins/genetics/metabolism ; Hydrogen Peroxide/pharmacology ; Iron/metabolism ; Nostoc/classification/drug effects/*genetics/*metabolism ; Oxidants/pharmacology ; Phylogeny ; Sequence Alignment ; }, abstract = {Ferritin-like proteins constitute a remarkably heterogeneous protein family, including ferritins, bacterioferritins and Dps proteins. The genome of the filamentous heterocyst-forming cyanobacterium Nostoc punctiforme encodes five ferritin-like proteins. In the present paper, we report a multidimensional characterization of these proteins. Our phylogenetic and bioinformatics analyses suggest both structural and physiological differences among the ferritin-like proteins. The expression of these five genes responded differently to hydrogen peroxide treatment, with a significantly higher rise in transcript level for Npun_F3730 as compared with the other four genes. A specific role for Npun_F3730 in the cells tolerance against hydrogen peroxide was also supported by the inactivation of Npun_F3730, Npun_R5701 and Npun_R6212; among these, only the ΔNpun_F3730 strain showed an increased sensitivity to hydrogen peroxide compared with wild type. Analysis of promoter-GFP reporter fusions of the ferritin-like genes indicated that Npun_F3730 and Npun_R5701 were expressed in all cell types of a diazotrophic culture, while Npun_F6212 was expressed specifically in heterocysts. Our study provides the first comprehensive analysis combining functional differentiation and cellular specificity within this important group of proteins in a multicellular cyanobacterium.}, } @article {pmid23990875, year = {2013}, author = {Schunck, H and Lavik, G and Desai, DK and Großkopf, T and Kalvelage, T and Löscher, CR and Paulmier, A and Contreras, S and Siegel, H and Holtappels, M and Rosenstiel, P and Schilhabel, MB and Graco, M and Schmitz, RA and Kuypers, MM and Laroche, J}, title = {Giant hydrogen sulfide plume in the oxygen minimum zone off Peru supports chemolithoautotrophy.}, journal = {PloS one}, volume = {8}, number = {8}, pages = {e68661}, pmid = {23990875}, issn = {1932-6203}, mesh = {Bacteria/*genetics/isolation & purification/metabolism ; Biomass ; Carbon Cycle ; Carbon Dioxide/chemistry ; Chemoautotrophic Growth/*physiology ; Cluster Analysis ; Colloids/chemistry ; Ecosystem ; Flow Cytometry/methods ; Genome, Bacterial ; Hydrogen Sulfide/*chemistry ; Nitrogen/chemistry ; Oxygen/*chemistry ; Pacific Ocean ; Peru ; Phylogeny ; Seawater/*chemistry ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Sulfides/chemistry ; Water Microbiology ; }, abstract = {In Eastern Boundary Upwelling Systems nutrient-rich waters are transported to the ocean surface, fuelling high photoautotrophic primary production. Subsequent heterotrophic decomposition of the produced biomass increases the oxygen-depletion at intermediate water depths, which can result in the formation of oxygen minimum zones (OMZ). OMZs can sporadically accumulate hydrogen sulfide (H2S), which is toxic to most multicellular organisms and has been implicated in massive fish kills. During a cruise to the OMZ off Peru in January 2009 we found a sulfidic plume in continental shelf waters, covering an area >5500 km(2), which contained ∼2.2×10(4) tons of H2S. This was the first time that H2S was measured in the Peruvian OMZ and with ∼440 km(3) the largest plume ever reported for oceanic waters. We assessed the phylogenetic and functional diversity of the inhabiting microbial community by high-throughput sequencing of DNA and RNA, while its metabolic activity was determined with rate measurements of carbon fixation and nitrogen transformation processes. The waters were dominated by several distinct γ-, δ- and ε-proteobacterial taxa associated with either sulfur oxidation or sulfate reduction. Our results suggest that these chemolithoautotrophic bacteria utilized several oxidants (oxygen, nitrate, nitrite, nitric oxide and nitrous oxide) to detoxify the sulfidic waters well below the oxic surface. The chemolithoautotrophic activity at our sampling site led to high rates of dark carbon fixation. Assuming that these chemolithoautotrophic rates were maintained throughout the sulfidic waters, they could be representing as much as ∼30% of the photoautotrophic carbon fixation. Postulated changes such as eutrophication and global warming, which lead to an expansion and intensification of OMZs, might also increase the frequency of sulfidic waters. We suggest that the chemolithoautotrophically fixed carbon may be involved in a negative feedback loop that could fuel further sulfate reduction and potentially stabilize the sulfidic OMZ waters.}, } @article {pmid23986111, year = {2013}, author = {Brown, MW and Sharpe, SC and Silberman, JD and Heiss, AA and Lang, BF and Simpson, AG and Roger, AJ}, title = {Phylogenomics demonstrates that breviate flagellates are related to opisthokonts and apusomonads.}, journal = {Proceedings. Biological sciences}, volume = {280}, number = {1769}, pages = {20131755}, pmid = {23986111}, issn = {1471-2954}, support = {MOP-62809//Canadian Institutes of Health Research/Canada ; }, mesh = {Ecosystem ; Estuaries ; Eukaryota/*classification/*genetics/ultrastructure ; Evolution, Molecular ; Genes, rRNA ; Geologic Sediments ; Molecular Sequence Data ; *Phylogeny ; RNA, Protozoan/genetics/metabolism ; Sequence Analysis, RNA ; }, abstract = {Most eukaryotic lineages belong to one of a few major groups. However, several protistan lineages have not yet been robustly placed in any of these groups. Both the breviates and apusomonads are two such lineages that appear to be related to the Amoebozoa and Opisthokonta (i.e. the 'unikonts' or Amorphea); however, their precise phylogenetic positions remain unclear. Here, we describe a novel microaerophilic breviate, Pygsuia biforma gen. nov. sp. nov., isolated from a hypoxic estuarine sediment. Ultrastructurally, this species resembles the breviate genera Breviata and Subulatomonas but has two cell morphologies, adherent and swimming. Phylogenetic analyses of the small sub-unit rRNA gene show that Pygsuia is the sister to the other breviates. We constructed a 159-protein supermatrix, including orthologues identified in RNA-seq data from Pygsuia. Phylogenomic analyses of this dataset show that breviates, apusomonads and Opisthokonta form a strongly supported major eukaryotic grouping we name the Obazoa. Although some phylogenetic methods disagree, the balance of evidence suggests that the breviate lineage forms the deepest branch within Obazoa. We also found transcripts encoding a nearly complete integrin adhesome from Pygsuia, indicating that this protein complex involved in metazoan multicellularity may have evolved earlier in eukaryote evolution than previously thought.}, } @article {pmid23980147, year = {2013}, author = {Alessandri, K and Sarangi, BR and Gurchenkov, VV and Sinha, B and Kießling, TR and Fetler, L and Rico, F and Scheuring, S and Lamaze, C and Simon, A and Geraldo, S and Vignjevic, D and Doméjean, H and Rolland, L and Funfak, A and Bibette, J and Bremond, N and Nassoy, P}, title = {Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {37}, pages = {14843-14848}, pmid = {23980147}, issn = {1091-6490}, mesh = {Alginates ; Animals ; Biomechanical Phenomena ; Capsules ; Cell Count ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Disease Progression ; Elasticity ; Glucuronic Acid ; HeLa Cells ; Hexuronic Acids ; Humans ; Mechanotransduction, Cellular ; Mice ; Microfluidic Analytical Techniques/instrumentation ; Neoplasm Invasiveness/*pathology/*physiopathology ; Spheroids, Cellular/*pathology/*physiology ; Tumor Microenvironment ; }, abstract = {Deciphering the multifactorial determinants of tumor progression requires standardized high-throughput preparation of 3D in vitro cellular assays. We present a simple microfluidic method based on the encapsulation and growth of cells inside permeable, elastic, hollow microspheres. We show that this approach enables mass production of size-controlled multicellular spheroids. Due to their geometry and elasticity, these microcapsules can uniquely serve as quantitative mechanical sensors to measure the pressure exerted by the expanding spheroid. By monitoring the growth of individual encapsulated spheroids after confluence, we dissect the dynamics of pressure buildup toward a steady-state value, consistent with the concept of homeostatic pressure. In turn, these confining conditions are observed to increase the cellular density and affect the cellular organization of the spheroid. Postconfluent spheroids exhibit a necrotic core cemented by a blend of extracellular material and surrounded by a rim of proliferating hypermotile cells. By performing invasion assays in a collagen matrix, we report that peripheral cells readily escape preconfined spheroids and cell-cell cohesivity is maintained for freely growing spheroids, suggesting that mechanical cues from the surrounding microenvironment may trigger cell invasion from a growing tumor. Overall, our technology offers a unique avenue to produce in vitro cell-based assays useful for developing new anticancer therapies and to investigate the interplay between mechanics and growth in tumor evolution.}, } @article {pmid23978389, year = {2013}, author = {Nishihama, R and Kohchi, T}, title = {Evolutionary insights into photoregulation of the cell cycle in the green lineage.}, journal = {Current opinion in plant biology}, volume = {16}, number = {5}, pages = {630-637}, doi = {10.1016/j.pbi.2013.07.006}, pmid = {23978389}, issn = {1879-0356}, mesh = {Biological Evolution ; Cell Cycle/radiation effects ; Chlorophyta/genetics/growth & development/radiation effects ; Cytokinins/metabolism ; Embryophyta/genetics/growth & development/radiation effects ; *Gene Expression Regulation, Plant ; Indoleacetic Acids/metabolism ; Light ; Photoreceptors, Plant/genetics/metabolism ; *Plant Development ; Plant Growth Regulators/metabolism ; Plants/genetics/*radiation effects ; *Signal Transduction ; }, abstract = {Plant growth depends solely on light energy, which drives photosynthesis. Thus, linking growth control to light signals during certain developmental events, such as seed or spore germination and organ formation, is a crucial feature that plants evolved to use energy efficiently. How light controls the cell cycle depends on growth habitats, body plans (unicellular vs. multicellular), and photosensors. For example, the photosensors mediating light signaling to promote cell division appear to differ between green algae and land plants. In this review, we focus on cell-cycle regulation by light and discuss the transition of its molecular mechanisms during evolution. Recent advances show that light-dependent cell-cycle control involves global changes in transcription of cell-cycle genes, and is mediated by auxin and cytokinin.}, } @article {pmid23959164, year = {2013}, author = {Izumi, H and Sagulenko, E and Webb, RI and Fuerst, JA}, title = {Isolation and diversity of planctomycetes from the sponge Niphates sp., seawater, and sediment of Moreton Bay, Australia.}, journal = {Antonie van Leeuwenhoek}, volume = {104}, number = {4}, pages = {533-546}, doi = {10.1007/s10482-013-0003-5}, pmid = {23959164}, issn = {1572-9699}, mesh = {Animals ; Australia ; Bacteria/*classification/*genetics/ultrastructure ; Bays/microbiology ; Geologic Sediments/microbiology ; Phylogeny ; Porifera/*microbiology/ultrastructure ; RNA, Ribosomal, 16S ; Seawater/microbiology ; }, abstract = {Planctomycetes are ubiquitous in marine environment and were reported to occur in association with multicellular eukaryotic organisms such as marine macroalgae and invertebrates. Here, we investigate planctomycetes associated with the marine sponge Niphates sp. from the sub-tropical Australian coast by assessing their diversity using culture-dependent and -independent approaches based on the 16S rRNA gene. The culture-dependent approach resulted in the isolation of a large collection of diverse planctomycetes including some novel lineages of Planctomycetes from the sponge as well as sediment and seawater of Moreton Bay where this sponge occurs. The characterization of these novel planctomycetes revealed that cells of one unique strain do not possess condensed nucleoids, a phenotype distinct from other planctomycetes. In addition, a culture-independent clone library approach identified unique planctomycete 16S rRNA gene sequences closely related to other sponge-derived sequences. The analysis of tissue of the sponge Niphates sp. showed that the mesohyl of the sponge is almost devoid of microbial cells, indicating this species is in the group of 'low microbial abundant' (LMA) sponges. The unique planctomycete 16S rRNA gene sequences identified in this study were phylogenetically closely related to sequences from LMA sponges in other published studies. This study has revealed new insights into the diversity of planctomycetes in the marine environment and the association of planctomycetes with marine sponges.}, } @article {pmid23950149, year = {2013}, author = {Cole, JK and Gieler, BA and Heisler, DL and Palisoc, MM and Williams, AJ and Dohnalkova, AC and Ming, H and Yu, TT and Dodsworth, JA and Li, WJ and Hedlund, BP}, title = {Kallotenue papyrolyticum gen. nov., sp. nov., a cellulolytic and filamentous thermophile that represents a novel lineage (Kallotenuales ord. nov., Kallotenuaceae fam. nov.) within the class Chloroflexia.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {63}, number = {Pt 12}, pages = {4675-4682}, doi = {10.1099/ijs.0.053348-0}, pmid = {23950149}, issn = {1466-5034}, mesh = {Cellulose/*metabolism ; Chloroflexi/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Hot Springs/*microbiology ; Molecular Sequence Data ; Nevada ; Peptidoglycan/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Several closely related, thermophilic and cellulolytic bacterial strains, designated JKG1(T), JKG2, JKG3, JKG4 and JKG5, were isolated from a cellulolytic enrichment (corn stover) incubated in the water column of Great Boiling Spring, NV. Strain JKG1(T) had cells of diameter 0.7-0.9 µm and length ~2.0 µm that formed non-branched, multicellular filaments reaching >300 µm. Spores were not formed and dense liquid cultures were red. The temperature range for growth was 45-65 °C, with an optimum of 55 °C. The pH range for growth was pH 5.6-9.0, with an optimum of pH 7.5. JKG1(T) grew as an aerobic heterotroph, utilizing glucose, sucrose, xylose, arabinose, cellobiose, CM-cellulose, filter paper, microcrystalline cellulose, xylan, starch, Casamino acids, tryptone, peptone, yeast extract, acetate, citrate, lactate, pyruvate and glycerol as sole carbon sources, and was not observed to photosynthesize. The cells stained Gram-negative. Phylogenetic analysis using 16S rRNA gene sequences placed the new isolates in the class Chloroflexia, but distant from other cultivated members, with the highest sequence identity of 82.5 % to Roseiflexus castenholzii. The major quinone was menaquinone-9; no ubiquinones were detected. The major cellular fatty acids (>5 %) were C18 : 0, anteiso-C17 : 0, iso-C18 : 0, iso-C17 : 0, C16 : 0, iso-C16 : 0 and C17 : 0. The peptidoglycan amino acids were alanine, ornithine, glutamic acid, serine and asparagine. Whole-cell sugars included mannose, rhamnose, glucose, galactose, ribose, arabinose and xylose. Morphological, phylogenetic and chemotaxonomic results suggest that JKG1(T) is representative of a new lineage within the class Chloroflexia, which we propose to designate Kallotenue papyrolyticum gen. nov., sp. nov., Kallotenuaceae fam. nov., Kallotenuales ord. nov. The type strain of Kallotenue papyrolyticum gen. nov., sp. nov. is JKG1(T) (= DSM 26889(T) = JCM 19132(T)).}, } @article {pmid23946353, year = {2013}, author = {Boavida, LC and Qin, P and Broz, M and Becker, JD and McCormick, S}, title = {Arabidopsis tetraspanins are confined to discrete expression domains and cell types in reproductive tissues and form homo- and heterodimers when expressed in yeast.}, journal = {Plant physiology}, volume = {163}, number = {2}, pages = {696-712}, pmid = {23946353}, issn = {1532-2548}, mesh = {Amino Acid Sequence ; Animals ; Arabidopsis/*cytology/genetics/*metabolism ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Cell Membrane/metabolism ; Gene Expression Regulation, Plant ; Germ Cells, Plant/cytology/metabolism ; Green Fluorescent Proteins/metabolism ; Molecular Sequence Data ; *Organ Specificity ; Phylogeny ; *Protein Multimerization ; Protein Transport ; Reproduction/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Saccharomyces cerevisiae/*metabolism ; Sequence Alignment ; Subcellular Fractions/metabolism ; Tetraspanins/chemistry/genetics/*metabolism ; }, abstract = {Tetraspanins are evolutionary conserved transmembrane proteins present in all multicellular organisms. In animals, they are known to act as central organizers of membrane complexes and thought to facilitate diverse biological processes, such as cell proliferation, movement, adhesion, and fusion. The genome of Arabidopsis (Arabidopsis thaliana) encodes 17 members of the tetraspanin family; however, little is known about their functions in plant development. Here, we analyzed their phylogeny, protein topology, and domain structure and surveyed their expression and localization patterns in reproductive tissues. We show that, despite their low sequence identity with metazoan tetraspanins, plant tetraspanins display the typical structural topology and most signature features of tetraspanins in other multicellular organisms. Arabidopsis tetraspanins are expressed in diverse tissue domains or cell types in reproductive tissues, and some accumulate at the highest levels in response to pollination in the transmitting tract and stigma, male and female gametophytes and gametes. Arabidopsis tetraspanins are preferentially targeted to the plasma membrane, and they variously associate with specialized membrane domains, in a polarized fashion, to intercellular contacts or plasmodesmata. A membrane-based yeast (Saccharomyces cerevisiae) two-hybrid system established that tetraspanins can physically interact, forming homo- and heterodimer complexes. These results, together with a likely genetic redundancy, suggest that, similar to their metazoan counterparts, plant tetraspanins might be involved in facilitating intercellular communication, whose functions might be determined by the composition of tetraspanin complexes and their binding partners at the cell surface of specific cell types.}, } @article {pmid23945682, year = {2013}, author = {Stewart, AJ and Plotkin, JB}, title = {The evolution of complex gene regulation by low-specificity binding sites.}, journal = {Proceedings. Biological sciences}, volume = {280}, number = {1768}, pages = {20131313}, pmid = {23945682}, issn = {1471-2954}, mesh = {Binding Sites ; *Evolution, Molecular ; *Gene Expression Regulation ; *Gene Regulatory Networks ; Models, Genetic ; Mutation ; }, abstract = {Requirements for gene regulation vary widely both within and among species. Some genes are constitutively expressed, whereas other genes require complex regulatory control. Transcriptional regulation is often controlled by a module of multiple transcription factor binding sites that, in combination, mediate the expression of a target gene. Here, we study how such regulatory modules evolve in response to natural selection. Using a population-genetic model, we show that complex regulatory modules which contain a larger number of binding sites must employ binding motifs that are less specific, on average, compared with smaller regulatory modules. This effect is extremely general, and it holds regardless of the selected binding logic that a module experiences. We attribute this phenomenon to the inability of stabilizing selection to maintain highly specific sites in large regulatory modules. Our analysis helps to explain broad empirical trends in the Saccharomyces cerevisiae regulatory network: those genes with a greater number of distinct transcriptional regulators feature less-specific binding motifs, compared with genes with fewer regulators. Our results also help to explain empirical trends in module size and motif specificity across species, ranging from prokaryotes to single-cellular and multi-cellular eukaryotes.}, } @article {pmid23943356, year = {2013}, author = {Dick, SA and Megeney, LA}, title = {Cell death proteins: an evolutionary role in cellular adaptation before the advent of apoptosis.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {11}, pages = {974-983}, doi = {10.1002/bies.201300052}, pmid = {23943356}, issn = {1521-1878}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Adaptation, Physiological/*physiology ; Animals ; Apoptosis/*physiology ; Apoptosis Regulatory Proteins/genetics/*physiology ; Caspases/metabolism ; Cell Differentiation ; Eukaryota/cytology/metabolism ; Evolution, Molecular ; Phosphatidylserines/metabolism ; Signal Transduction ; }, abstract = {Programmed cell death (PCD) or apoptosis is a broadly conserved phenomenon in metazoans, whereby activation of canonical signal pathways induces an ordered dismantling and death of a cell. Paradoxically, the constituent proteins and pathways of PCD (most notably the metacaspase/caspase protease mediated signal pathways) have been demonstrated to retain non-death functions across all phyla including yeast, nematodes, drosophila, and mammals. The ancient conservation of both death and non-death functions of PCD proteins raises an interesting evolutionary conundrum: was the primordial intent of these factors to induce cell death or to regulate other cellular adaptations? Here, we propose the hypothesis that apoptotic behavior of PCD proteins evolved or were co-opted from core non-death functions.}, } @article {pmid23942320, year = {2013}, author = {Suga, H and Chen, Z and de Mendoza, A and Sebé-Pedrós, A and Brown, MW and Kramer, E and Carr, M and Kerner, P and Vervoort, M and Sánchez-Pons, N and Torruella, G and Derelle, R and Manning, G and Lang, BF and Russ, C and Haas, BJ and Roger, AJ and Nusbaum, C and Ruiz-Trillo, I}, title = {The Capsaspora genome reveals a complex unicellular prehistory of animals.}, journal = {Nature communications}, volume = {4}, number = {}, pages = {2325}, pmid = {23942320}, issn = {2041-1723}, support = {HG003067-05/HG/NHGRI NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; HG003067-09/HG/NHGRI NIH HHS/United States ; 206883/ERC_/European Research Council/International ; HG003067-07/HG/NHGRI NIH HHS/United States ; HG003067-06/HG/NHGRI NIH HHS/United States ; HG003067-10/HG/NHGRI NIH HHS/United States ; HG003067-08/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/genetics ; Base Sequence ; Biological Evolution ; Cell Adhesion/genetics ; Choanoflagellata/*genetics/metabolism ; Evolution, Molecular ; Genome ; Intercellular Signaling Peptides and Proteins/*genetics/metabolism ; Mesomycetozoea/*genetics ; Mitochondria/genetics ; Phylogeny ; Protein Structure, Tertiary/genetics ; Sequence Analysis, DNA ; Signal Transduction/genetics ; Transcription, Genetic/genetics ; }, abstract = {To reconstruct the evolutionary origin of multicellular animals from their unicellular ancestors, the genome sequences of diverse unicellular relatives are essential. However, only the genome of the choanoflagellate Monosiga brevicollis has been reported to date. Here we completely sequence the genome of the filasterean Capsaspora owczarzaki, the closest known unicellular relative of metazoans besides choanoflagellates. Analyses of this genome alter our understanding of the molecular complexity of metazoans' unicellular ancestors showing that they had a richer repertoire of proteins involved in cell adhesion and transcriptional regulation than previously inferred only with the choanoflagellate genome. Some of these proteins were secondarily lost in choanoflagellates. In contrast, most intercellular signalling systems controlling development evolved later concomitant with the emergence of the first metazoans. We propose that the acquisition of these metazoan-specific developmental systems and the co-option of pre-existing genes drove the evolutionary transition from unicellular protists to metazoans.}, } @article {pmid23932204, year = {2013}, author = {Small, ID and Rackham, O and Filipovska, A}, title = {Organelle transcriptomes: products of a deconstructed genome.}, journal = {Current opinion in microbiology}, volume = {16}, number = {5}, pages = {652-658}, doi = {10.1016/j.mib.2013.07.011}, pmid = {23932204}, issn = {1879-0364}, mesh = {Animals ; Chloroplasts/*genetics/physiology ; Mitochondria/*genetics/physiology ; Plant Cells/*physiology ; Plants/genetics ; *Transcriptome ; }, abstract = {Genetic drift and mutational pressure have shaped the evolution of mitochondrial and chloroplast genomes, giving rise to mechanisms that regulate their gene expression, which often differ from those in their prokaryotic ancestors. Advances in next generation sequencing technologies have enabled highly detailed characterization of organelle transcriptomes and the discovery of new transcripts and mechanisms for controlling gene expression. Here we discuss the common features of organelle transcriptomes that stem from their prokaryotic origin and some of the new innovations that are unique to organelles of multicellular organisms.}, } @article {pmid23913097, year = {2013}, author = {Tarver, JE and Sperling, EA and Nailor, A and Heimberg, AM and Robinson, JM and King, BL and Pisani, D and Donoghue, PC and Peterson, KJ}, title = {miRNAs: small genes with big potential in metazoan phylogenetics.}, journal = {Molecular biology and evolution}, volume = {30}, number = {11}, pages = {2369-2382}, doi = {10.1093/molbev/mst133}, pmid = {23913097}, issn = {1537-1719}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Base Sequence ; Bayes Theorem ; Conserved Sequence ; *Evolution, Molecular ; Gene Regulatory Networks ; Genome ; Humans ; MicroRNAs/*genetics/*metabolism ; *Phylogeny ; Secondary Metabolism/genetics ; Species Specificity ; }, abstract = {microRNAs (miRNAs) are a key component of gene regulatory networks and have been implicated in the regulation of virtually every biological process found in multicellular eukaryotes. What makes them interesting from a phylogenetic perspective is the high conservation of primary sequence between taxa, their accrual in metazoan genomes through evolutionary time, and the rarity of secondary loss in most metazoan taxa. Despite these properties, the use of miRNAs as phylogenetic markers has not yet been discussed within a clear conceptual framework. Here we highlight five properties of miRNAs that underlie their utility in phylogenetics: 1) The processes of miRNA biogenesis enable the identification of novel miRNAs without prior knowledge of sequence; 2) The continuous addition of miRNA families to metazoan genomes through evolutionary time; 3) The low level of secondary gene loss in most metazoan taxa; 4) The low substitution rate in the mature miRNA sequence; and 5) The small probability of convergent evolution of two miRNAs. Phylogenetic analyses using both Bayesian and parsimony methods on a eumetazoan miRNA data set highlight the potential of miRNAs to become an invaluable new tool, especially when used as an additional line of evidence, to resolve previously intractable nodes within the tree of life.}, } @article {pmid23910661, year = {2013}, author = {Ho, HI and Hirose, S and Kuspa, A and Shaulsky, G}, title = {Kin recognition protects cooperators against cheaters.}, journal = {Current biology : CB}, volume = {23}, number = {16}, pages = {1590-1595}, pmid = {23910661}, issn = {1879-0445}, support = {CA125123/CA/NCI NIH HHS/United States ; AI036211/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; R01 GM098276/GM/NIGMS NIH HHS/United States ; R01 GM084992/GM/NIGMS NIH HHS/United States ; RR024574/RR/NCRR NIH HHS/United States ; }, mesh = {*Biological Evolution ; Dictyostelium/cytology/*genetics ; Membrane Proteins/*genetics/metabolism ; Microscopy, Fluorescence ; Organisms, Genetically Modified/genetics ; Phenotype ; Protozoan Proteins/*genetics/metabolism ; Reproduction ; Spores, Protozoan/cytology/genetics ; }, abstract = {The evolution of sociality and altruism is enigmatic because cooperators are constantly threatened by cheaters who benefit from cooperation without incurring its full cost [1, 2]. Kin recognition is the ability to recognize and cooperate with genetically close relatives. It has also been proposed as a potential mechanism that limits cheating [3, 4], but there has been no direct experimental support for that possibility. Here we show that kin recognition protects cooperators against cheaters. The social amoebae Dictyostelium discoideum cooperate by forming multicellular aggregates that develop into fruiting bodies of viable spores and dead stalk cells. Cheaters preferentially differentiate into spores while their victims die as stalk cells in chimeric aggregates. We engineered syngeneic cheaters and victims that differed only in their kin-recognition genes, tgrB1 and tgrC1, and in a single cheater allele and found that the victims escaped exploitation by different types of nonkin cheaters. This protection depends on kin-recognition-mediated segregation because it is compromised when we disrupt strain segregation. These findings provide direct evidence for the role of kin recognition in cheater control and suggest a mechanism for the maintenance of stable cooperative systems.}, } @article {pmid23907222, year = {2013}, author = {Kang, JY and Chun, J and Choi, A and Cho, JC and Jahng, KY}, title = {Nibrella saemangeumensis gen. nov., sp. nov. and Nibrella viscosa sp. nov., novel members of the family Cytophagaceae, isolated from seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {63}, number = {Pt 12}, pages = {4508-4514}, doi = {10.1099/ijs.0.053439-0}, pmid = {23907222}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Molecular Sequence Data ; Phosphatidylethanolamines/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Spermidine/chemistry ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Two strains, designated GCR0103(T) and GYR3121(T), were isolated from seawater of the Saemangeum Embankment in Jeollabuk-do, Korea. The cells of the two strains were Gram-reaction-negative and non-motile, and formed multicellular filaments. The colonies of the two strains were pink-pigmented and able to grow at 15-37 °C (optimum 25 °C) on R2A and NA medium. Strains GCR0103(T) and GYR3121(T) grew at pH 6.5-10 (optimum pH 7.5) and pH 5.5-9.5 (optimum pH 7.5), and within NaCl ranges of 0-0.4% and 0-1%, respectively. The polar lipid profiles of the two strains contained phosphatidylethanolamine, five unknown aminolipids, an unknown phospholipid and four or five unknown lipids. The DNA G+C contents of strains GCR0103(T) and GYR3121(T) were 56.0 and 54.5 mol%, respectively. The respiratory quinone detected in both strains was MK-7. The 16S rRNA gene sequence similarity between GCR0103(T) and GYR3121(T) was 95.5 %. The 16S rRNA gene sequence similarities of the two strains to closely related reference strains were less than 89 %. Phylogenetic analysis based on 16S rRNA genes showed that GCR0103(T) and GYR3121(T) formed a distinct phyletic line in the family Cytophagaceae. On the basis of the phenotypic, chemotaxonomic and phylogenetic properties, strains GCR0103(T) and GYR3121(T) represent two novel species in a new genus within the family Cytophagaceae, for which the names Nibrella saemangeumensis gen. nov., sp. nov. and Nibrella viscosa sp. nov. are proposed. The type strain of Nibrella saemangeumensis is GCR0103(T) (= KACC 16453(T) = JCM 17927(T)) and the type strain of Nibrella viscosa is GYR3121(T) (= KACC 16447(T) = JCM 17925(T)).}, } @article {pmid23902772, year = {2013}, author = {Garner, JM and Fan, M and Yang, CH and Du, Z and Sims, M and Davidoff, AM and Pfeffer, LM}, title = {Constitutive activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor κB signaling in glioblastoma cancer stem cells regulates the Notch pathway.}, journal = {The Journal of biological chemistry}, volume = {288}, number = {36}, pages = {26167-26176}, pmid = {23902772}, issn = {1083-351X}, support = {R01 CA133322/CA/NCI NIH HHS/United States ; R01 CA140346/CA/NCI NIH HHS/United States ; CA133322/CA/NCI NIH HHS/United States ; 21766//PHS HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Glioblastoma/genetics/*metabolism/pathology ; Humans ; Mice ; NF-kappa B/genetics/*metabolism ; Neoplasm Proteins/genetics/*metabolism ; Neoplastic Stem Cells/*metabolism/pathology ; Receptors, Notch/genetics/*metabolism ; STAT3 Transcription Factor/*biosynthesis/genetics ; *Signal Transduction ; Spheroids, Cellular/metabolism/pathology ; Up-Regulation/genetics ; }, abstract = {Malignant gliomas are locally aggressive, highly vascular tumors that have a dismal prognosis, and present therapies provide little improvement in the disease course and outcome. Many types of malignancies, including glioblastoma, originate from a population of cancer stem cells (CSCs) that are able to initiate and maintain tumors. Although CSCs only represent a small fraction of cells within a tumor, their high tumor-initiating capacity and therapeutic resistance drives tumorigenesis. Therefore, it is imperative to identify pathways associated with CSCs to devise strategies to selectively target them. In this study, we describe a novel relationship between glioblastoma CSCs and the Notch pathway, which involves the constitutive activation of STAT3 and NF-κB signaling. Glioma CSCs were isolated and maintained in vitro using an adherent culture system, and the biological properties were compared with the traditional cultures of CSCs grown as multicellular spheres under nonadherent culture conditions. Interestingly, both adherent and spheroid glioma CSCs show constitutive activation of the STAT3/NF-κB signaling pathway and up-regulation of STAT3- and NF-κB-dependent genes. Gene expression profiling also identified components of the Notch pathway as being deregulated in glioma CSCs, and the deregulated expression of these genes was sensitive to treatment with STAT3 and NF-κB inhibitors. This finding is particularly important because Notch signaling appears to play a key role in CSCs in a variety of cancers and controls cell fate determination, survival, proliferation, and the maintenance of stem cells. The constitutive activation of STAT3 and NF-κB signaling pathways that leads to the regulation of Notch pathway genes in glioma CSCs identifies novel therapeutic targets for the treatment of glioma.}, } @article {pmid23899506, year = {2013}, author = {Schallenberg-Rüdinger, M and Lenz, H and Polsakiewicz, M and Gott, JM and Knoop, V}, title = {A survey of PPR proteins identifies DYW domains like those of land plant RNA editing factors in diverse eukaryotes.}, journal = {RNA biology}, volume = {10}, number = {9}, pages = {1549-1556}, pmid = {23899506}, issn = {1555-8584}, mesh = {Acanthamoeba castellanii/genetics/metabolism ; Embryophyta/*genetics/metabolism ; *Eukaryota ; Naegleria/genetics ; Nitella/genetics/metabolism ; Organelles/genetics/metabolism ; Phylogeny ; Physarum polycephalum/genetics/metabolism ; Plant Proteins/genetics/*metabolism ; Prokaryotic Cells/metabolism ; Protein Structure, Tertiary ; *RNA Editing ; RNA-Binding Proteins/genetics/*metabolism ; }, abstract = {The pentatricopeptide repeat modules of PPR proteins are key to their sequence-specific binding to RNAs. Gene families encoding PPR proteins are greatly expanded in land plants where hundreds of them participate in RNA maturation, mainly in mitochondria and chloroplasts. Many plant PPR proteins contain additional carboxyterminal domains and have been identified as essential factors for specific events of C-to-U RNA editing, which is abundant in the two endosymbiotic plant organelles. Among those carboxyterminal domain additions to plant PPR proteins, the so-called DYW domain is particularly interesting given its similarity to cytidine deaminases. The frequency of organelle C-to-U RNA editing and the diversity of DYW-type PPR proteins correlate well in plants and both were recently identified outside of land plants, in the protist Naegleria gruberi. Here we present a systematic survey of PPR protein genes and report on the identification of additional DYW-type PPR proteins in the protists Acanthamoeba castellanii, Malawimonas jakobiformis, and Physarum polycephalum. Moreover, DYW domains were also found in basal branches of multi-cellular lineages outside of land plants, including the alga Nitella flexilis and the rotifers Adineta ricciae and Philodina roseola. Intriguingly, the well-characterized and curious patterns of mitochondrial RNA editing in the slime mold Physarum also include examples of C-to-U changes. Finally, we identify candidate sites for mitochondrial RNA editing in Malawimonas, further supporting a link between DYW-type PPR proteins and C-to-U editing, which may have remained hitherto unnoticed in additional eukaryote lineages.}, } @article {pmid23894089, year = {2013}, author = {Rainer, PP and Primessnig, U and Harenkamp, S and Doleschal, B and Wallner, M and Fauler, G and Stojakovic, T and Wachter, R and Yates, A and Groschner, K and Trauner, M and Pieske, BM and von Lewinski, D}, title = {Bile acids induce arrhythmias in human atrial myocardium--implications for altered serum bile acid composition in patients with atrial fibrillation.}, journal = {Heart (British Cardiac Society)}, volume = {99}, number = {22}, pages = {1685-1692}, doi = {10.1136/heartjnl-2013-304163}, pmid = {23894089}, issn = {1468-201X}, support = {F 3517/FWF_/Austrian Science Fund FWF/Austria ; P 19118/FWF_/Austrian Science Fund FWF/Austria ; W 1226/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Aged ; Animals ; Atrial Fibrillation/*blood/*etiology ; Bile Acids and Salts/*blood/chemistry/*pharmacology/physiology ; Cardiac Electrophysiology ; Female ; Heart Atria/*drug effects ; Humans ; Male ; Mice ; Myocytes, Cardiac/*drug effects/*physiology ; Taurocholic Acid/pharmacology ; Ursodeoxycholic Acid/pharmacology ; }, abstract = {OBJECTIVE: High bile acid serum concentrations have been implicated in cardiac disease, particularly in arrhythmias. Most data originate from in vitro studies and animal models. We tested the hypotheses that (1) high bile acid concentrations are arrhythmogenic in adult human myocardium, (2) serum bile acid concentrations and composition are altered in patients with atrial fibrillation (AF) and (3) the therapeutically used ursodeoxycholic acid has different effects than other potentially toxic bile acids.

METHODS AND RESULTS: Multicellular human atrial preparations ('trabeculae') were exposed to primary bile acids and the incidence of arrhythmic events was assessed. Bile acid concentrations were measured in serum samples from 250 patients and their association with AF and ECG parameters analysed. Additionally, we conducted electrophysiological studies in murine myocytes. Taurocholic acid (TCA) concentration-dependently induced arrhythmias in atrial trabeculae (14/28 at 300 µM TCA, p<0.01) while ursodeoxycholic acid did not. Patients with AF had significantly decreased serum levels of ursodeoxycholic acid conjugates and increased levels of non-ursodeoxycholic bile acids. In isolated myocytes, TCA depolarised the resting membrane potential, enhanced Na(+)/Ca(2+) exchanger (NCX) tail current density and induced afterdepolarisations. Inhibition of NCX prevented arrhythmias in atrial trabeculae.

CONCLUSIONS: High TCA concentrations induce arrhythmias in adult human atria while ursodeoxycholic acid does not. AF is associated with higher serum levels of non-ursodeoxycholic bile acid conjugates and low levels of ursodeoxycholic acid conjugates. These data suggest that higher levels of toxic (arrhythmogenic) and low levels of protective bile acids create a milieu with a decreased arrhythmic threshold and thus may facilitate arrhythmic events.}, } @article {pmid23885060, year = {2013}, author = {Blackstone, NW}, title = {Evolution and cell physiology. 2. The evolution of cell signaling: from mitochondria to Metazoa.}, journal = {American journal of physiology. Cell physiology}, volume = {305}, number = {9}, pages = {C909-15}, doi = {10.1152/ajpcell.00216.2013}, pmid = {23885060}, issn = {1522-1563}, mesh = {Animals ; *Biological Evolution ; Cell Physiological Phenomena/*physiology ; Humans ; Mitochondria/*physiology ; Signal Transduction/*physiology ; }, abstract = {The history of life is a history of levels-of-selection transitions. Each transition requires mechanisms that mediate conflict among the lower-level units. In the origins of multicellular eukaryotes, cell signaling is one such mechanism. The roots of cell signaling, however, may extend to the previous major transition, the origin of eukaryotes. Energy-converting protomitochondria within a larger cell allowed eukaryotes to transcend the surface-to-volume constraints inherent in the design of prokaryotes. At the same time, however, protomitochondria can selfishly allocate energy to their own replication. Metabolic signaling may have mediated this principal conflict in several ways. Variation of the protomitochondria was constrained by stoichiometry and strong metabolic demand (state 3) exerted by the protoeukaryote. Variation among protoeukaryotes was increased by the sexual stage of the life cycle, triggered by weak metabolic demand (state 4), resulting in stochastic allocation of protomitochondria to daughter cells. Coupled with selection, many selfish protomitochondria could thus be removed from the population. Hence, regulation of states 3 and 4, as, for instance, provided by the CO2/soluble adenylyl cyclase/cAMP pathway in mitochondria, was critical for conflict mediation. Subsequently, as multicellular eukaryotes evolved, metabolic signaling pathways employed by eukaryotes to mediate conflict within cells could now be co-opted into conflict mediation between cells. For example, in some fungi, the CO2/soluble adenylyl cyclase/cAMP pathway regulates the transition from yeast to forms with hyphae. In animals, this pathway regulates the maturation of sperm. While the particular features (sperm and hyphae) are distinct, both may involve between-cell conflicts that required mediation.}, } @article {pmid23875784, year = {2013}, author = {Ooi, HK and Ma, L}, title = {Modeling heterogeneous responsiveness of intrinsic apoptosis pathway.}, journal = {BMC systems biology}, volume = {7}, number = {}, pages = {65}, pmid = {23875784}, issn = {1752-0509}, mesh = {*Apoptosis ; *Models, Biological ; *Signal Transduction ; Stochastic Processes ; }, abstract = {BACKGROUND: Apoptosis is a cell suicide mechanism that enables multicellular organisms to maintain homeostasis and to eliminate individual cells that threaten the organism's survival. Dependent on the type of stimulus, apoptosis can be propagated by extrinsic pathway or intrinsic pathway. The comprehensive understanding of the molecular mechanism of apoptotic signaling allows for development of mathematical models, aiming to elucidate dynamical and systems properties of apoptotic signaling networks. There have been extensive efforts in modeling deterministic apoptosis network accounting for average behavior of a population of cells. Cellular networks, however, are inherently stochastic and significant cell-to-cell variability in apoptosis response has been observed at single cell level.

RESULTS: To address the inevitable randomness in the intrinsic apoptosis mechanism, we develop a theoretical and computational modeling framework of intrinsic apoptosis pathway at single-cell level, accounting for both deterministic and stochastic behavior. Our deterministic model, adapted from the well-accepted Fussenegger model, shows that an additional positive feedback between the executioner caspase and the initiator caspase plays a fundamental role in yielding the desired property of bistability. We then examine the impact of intrinsic fluctuations of biochemical reactions, viewed as intrinsic noise, and natural variation of protein concentrations, viewed as extrinsic noise, on behavior of the intrinsic apoptosis network. Histograms of the steady-state output at varying input levels show that the intrinsic noise could elicit a wider region of bistability over that of the deterministic model. However, the system stochasticity due to intrinsic fluctuations, such as the noise of steady-state response and the randomness of response delay, shows that the intrinsic noise in general is insufficient to produce significant cell-to-cell variations at physiologically relevant level of molecular numbers. Furthermore, the extrinsic noise represented by random variations of two key apoptotic proteins, namely Cytochrome C and inhibitor of apoptosis proteins (IAP), is modeled separately or in combination with intrinsic noise. The resultant stochasticity in the timing of intrinsic apoptosis response shows that the fluctuating protein variations can induce cell-to-cell stochastic variability at a quantitative level agreeing with experiments. Finally, simulations illustrate that the mean abundance of fluctuating IAP protein is positively correlated with the degree of cellular stochasticity of the intrinsic apoptosis pathway.

CONCLUSIONS: Our theoretical and computational study shows that the pronounced non-genetic heterogeneity in intrinsic apoptosis responses among individual cells plausibly arises from extrinsic rather than intrinsic origin of fluctuations. In addition, it predicts that the IAP protein could serve as a potential therapeutic target for suppression of the cell-to-cell variation in the intrinsic apoptosis responsiveness.}, } @article {pmid23864594, year = {2013}, author = {Noble, LM and Andrianopoulos, A}, title = {Reproductive competence: a recurrent logic module in eukaryotic development.}, journal = {Proceedings. Biological sciences}, volume = {280}, number = {1766}, pages = {20130819}, pmid = {23864594}, issn = {1471-2954}, mesh = {*Adaptation, Physiological ; Animals ; Ascomycota/*physiology ; Life Cycle Stages ; Plant Physiological Phenomena ; Reproduction ; }, abstract = {Developmental competence is the ability to differentiate in response to an appropriate stimulus, as first elaborated by Waddington in relation to organs and tissues. Competence thresholds operate at all levels of biological systems from the molecular (e.g. the cell cycle) to the ontological (e.g. metamorphosis and reproduction). Reproductive competence, an organismal process, is well studied in mammals (sexual maturity) and plants (vegetative phase change), though far less than later stages of terminal differentiation. The phenomenon has also been documented in multiple species of multicellular fungi, mostly in early, disparate literature, providing a clear example of physiological differentiation in the absence of morphological change. This review brings together data on reproductive competence in Ascomycete fungi, particularly the model filamentous fungus Aspergillus nidulans, contrasting mechanisms within Unikonts and plants. We posit reproductive competence is an elementary logic module necessary for coordinated development of multicellular organisms or functional units. This includes unitary multicellular life as well as colonial species both unicellular and multicellular (e.g. social insects such as ants). We discuss adaptive hypotheses for developmental and reproductive competence systems and suggest experimental work to address the evolutionary origins, generality and genetic basis of competence in the fungal kingdom.}, } @article {pmid23861491, year = {2013}, author = {Awan, AR and Manfredo, A and Pleiss, JA}, title = {Lariat sequencing in a unicellular yeast identifies regulated alternative splicing of exons that are evolutionarily conserved with humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {31}, pages = {12762-12767}, pmid = {23861491}, issn = {1091-6490}, support = {R01 GM098634/GM/NIGMS NIH HHS/United States ; GM098634/GM/NIGMS NIH HHS/United States ; }, mesh = {Alternative Splicing/*genetics ; *Evolution, Molecular ; Exons/*genetics ; Humans ; Schizosaccharomyces/*genetics ; *Sequence Analysis, DNA ; }, abstract = {Alternative splicing is a potent regulator of gene expression that vastly increases proteomic diversity in multicellular eukaryotes and is associated with organismal complexity. Although alternative splicing is widespread in vertebrates, little is known about the evolutionary origins of this process, in part because of the absence of phylogenetically conserved events that cross major eukaryotic clades. Here we describe a lariat-sequencing approach, which offers high sensitivity for detecting splicing events, and its application to the unicellular fungus, Schizosaccharomyces pombe, an organism that shares many of the hallmarks of alternative splicing in mammalian systems but for which no previous examples of exon-skipping had been demonstrated. Over 200 previously unannotated splicing events were identified, including examples of regulated alternative splicing. Remarkably, an evolutionary analysis of four of the exons identified here as subject to skipping in S. pombe reveals high sequence conservation and perfect length conservation with their homologs in scores of plants, animals, and fungi. Moreover, alternative splicing of two of these exons have been documented in multiple vertebrate organisms, making these the first demonstrations of identical alternative-splicing patterns in species that are separated by over 1 billion y of evolution.}, } @article {pmid23856377, year = {2014}, author = {Day, BJ}, title = {Antioxidant therapeutics: Pandora's box.}, journal = {Free radical biology & medicine}, volume = {66}, number = {}, pages = {58-64}, pmid = {23856377}, issn = {1873-4596}, support = {R01 HL084469/HL/NHLBI NIH HHS/United States ; U54 ES015678/ES/NIEHS NIH HHS/United States ; R01 ES012504/ES/NIEHS NIH HHS/United States ; HL59602/HL/NHLBI NIH HHS/United States ; HL075523/HL/NHLBI NIH HHS/United States ; R01 ES017582/ES/NIEHS NIH HHS/United States ; HL084469/HL/NHLBI NIH HHS/United States ; R01 HL075523/HL/NHLBI NIH HHS/United States ; ES015678/ES/NIEHS NIH HHS/United States ; ES017582/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Antioxidants/pharmacology/*therapeutic use ; Catalase/metabolism ; Humans ; Oxidative Stress/*drug effects ; Oxygen/metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Superoxide Dismutase/metabolism ; }, abstract = {Evolution has favored the utilization of dioxygen (O2) in the development of complex multicellular organisms. O2 is actually a toxic mutagenic gas that is highly oxidizing and combustible. It is thought that plants are largely to blame for polluting the earth's atmosphere with O2 owing to the development of photosynthesis by blue-green algae over 2 billion years ago. The rise of the plants and atmospheric O2 levels placed evolutionary stress on organisms to adapt or become extinct. This implies that all the surviving creatures on our planet are mutants that have adapted to the "abnormal biology" of O2. Much of the adaptation to the presence of O2 in biological systems comes from well-coordinated antioxidant and repair systems that focus on converting O2 to its most reduced form, water (H2O), and the repair and replacement of damaged cellular macromolecules. Biological systems have also harnessed O2's reactive properties for energy production, xenobiotic metabolism, and host defense and as a signaling messenger and redox modulator of a number of cell signaling pathways. Many of these systems involve electron transport systems and offer many different mechanisms by which antioxidant therapeutics can alternatively produce an antioxidant effect without directly scavenging oxygen-derived reactive species. It is likely that each agent will have a different set of mechanisms that may change depending on the model of oxidative stress, organ system, or disease state. An important point is that all biological processes of aerobes have coevolved with O2 and this creates a Pandora's box for trying to understand the mechanism(s) of action of antioxidants being developed as therapeutic agents.}, } @article {pmid23850579, year = {2013}, author = {Lv, J and Yang, T and Yang, H and Li, Z and Qin, P and Zhang, X and Liang, X and Li, J and Chen, Q}, title = {Identification of myb genes in Euplotes aediculatus may indicate an early evolutionary process.}, journal = {Gene}, volume = {530}, number = {2}, pages = {266-272}, doi = {10.1016/j.gene.2013.06.072}, pmid = {23850579}, issn = {1879-0038}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Euplotes/*genetics ; *Genes, myb ; Genomic Library ; Humans ; Molecular Sequence Data ; Multigene Family ; Oncogene Proteins v-myb/classification/*genetics ; Phylogeny ; Plants/genetics ; Protozoan Proteins/classification/*genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {The myb gene family encodes proteins characterized by a highly conserved DNA-binding domain and functions as transcription regulators. There are three myb genes in animals with three Myb-motif repeats, namely c-myb, A-myb, and B-myb. By contrast, plants possess an abundance of myb genes, the majority of which are of the type R2R3 (with two Myb-motifs). Few plant myb genes are of the type R1R2R3. Five new myb members in Euplotes were recently identified through degenerate polymerase chain reaction, which suggests that the myb gene is also a multi-member family in the unicellular protist kingdom as in other multi-cellular eukaryotes. The entire gene family further shows the presence of both R1R2R3- and R2R3-type myb. The phylogenic analysis provides concrete new evidence for the evolution of myb genes.}, } @article {pmid23850535, year = {2013}, author = {Marijuán, PC and del Moral, R and Navarro, J}, title = {On eukaryotic intelligence: signaling system's guidance in the evolution of multicellular organization.}, journal = {Bio Systems}, volume = {114}, number = {1}, pages = {8-24}, doi = {10.1016/j.biosystems.2013.06.005}, pmid = {23850535}, issn = {1872-8324}, mesh = {*Biological Evolution ; Cell Communication/*physiology ; Cell Cycle/*physiology ; Cytoskeleton/*physiology ; Eukaryotic Cells/*cytology/*physiology ; *Models, Biological ; Signal Transduction/*physiology ; }, abstract = {Communication with the environment is an essential characteristic of the living cell, even more when considering the origins and evolution of multicellularity. A number of changes and tinkering inventions were necessary in the evolutionary transition between prokaryotic and eukaryotic cells, which finally made possible the appearance of genuine multicellular organisms. In the study of this process, however, the transformations experimented by signaling systems themselves have been rarely object of analysis, obscured by other more conspicuous biological traits: incorporation of mitochondria, segregated nucleus, introns/exons, flagellum, membrane systems, etc. Herein a discussion of the main avenues of change from prokaryotic to eukaryotic signaling systems and a review of the signaling resources and strategies underlying multicellularity will be attempted. In the expansion of prokaryotic signaling systems, four main systemic resources were incorporated: molecular tools for detection of solutes, molecular tools for detection of solvent (Donnan effect), the apparatuses of cell-cycle control, and the combined system endocytosis/cytoskeleton. The multiple kinds of enlarged, mixed pathways that emerged made possible the eukaryotic revolution in morphological and physiological complexity. The massive incorporation of processing resources of electro-molecular nature, derived from the osmotic tools counteracting the Donnan effect, made also possible the organization of a computational tissue with huge information processing capabilities: the nervous system. In the central nervous systems of vertebrates, and particularly in humans, neurons have achieved both the highest level of molecular-signaling complexity and the highest degree of information-processing adaptability. Theoretically, it can be argued that there has been an accelerated pace of evolutionary change in eukaryotic signaling systems, beyond the other general novelties introduced by eukaryotic cells in their handling of DNA processes. Under signaling system's guidance, the whole processes of transcription, alternative splicing, mobile elements, and other elements of domain recombination have become closely intertwined and have propelled the differentiation capabilities of multicellular tissues and morphologies. An amazing variety of signaling and self-construction strategies have emerged out from the basic eukaryotic design of multicellular complexity, in millions and millions of new species evolved. This design can also be seen abstractly as a new kind of quasi-universal problem-solving 'engine' implemented at the biomolecular scale-providing the fundamentals of eukaryotic 'intelligence'. Analyzing in depth the problem-solving intelligence of eukaryotic cells would help to establish an integrative panorama of their information processing organization, and of their capability to handle the morphological and physiological complexity associated. Whether an informational updating of the venerable "cell theory" is feasible or not, becomes, at the time being - right in the middle of the massive data deluge/revolution from omic disciplines - a matter to careful consider.}, } @article {pmid23846861, year = {2014}, author = {Lintilhac, PM}, title = {The problem of morphogenesis: unscripted biophysical control systems in plants.}, journal = {Protoplasma}, volume = {251}, number = {1}, pages = {25-36}, pmid = {23846861}, issn = {1615-6102}, mesh = {Animals ; Cell Wall/*physiology ; Evolution, Molecular ; Plant Cells/physiology ; Plant Development/genetics/*physiology ; *Plant Physiological Phenomena ; }, abstract = {The relative simplicity of plant developmental systems, having evolved within the universal constraints imposed by the plant cell wall, may allow us to outline a consistent developmental narrative that is not currently possible in the animal kingdom. In this article, I discuss three aspects of the development of the mature form in plants, approaching them in terms of the role played by the biophysics and mechanics of the cell wall during growth. First, I discuss axis extension in terms of a loss of stability-based model of cell wall stress relaxation and I introduce the possibility that cell wall stress relaxation can be modeled as a binary switch. Second, I consider meristem shape and surface conformation as a controlling element in the morphogenetic circuitry of plant organogenesis at the apex. Third, I approach the issue of reproductive differentiation and propose that the multicellular sporangium, a universal feature of land plants, acts as a stress-mechanical lens, focusing growth-induced stresses to create a geometrically precise mechanical singularity that can serve as an inducing developmental signal triggering the initiation of reproductive differentiation. Lastly, I offer these three examples of biophysically integrated control processes as entry points into a narrative that provides an independent, nongenetic context for understanding the evolution of the apoplast and the morphogenetic ontogeny of multicellular land plants.}, } @article {pmid23835507, year = {2013}, author = {Reinders, J and Mirouze, M and Nicolet, J and Paszkowski, J}, title = {Parent-of-origin control of transgenerational retrotransposon proliferation in Arabidopsis.}, journal = {EMBO reports}, volume = {14}, number = {9}, pages = {823-828}, pmid = {23835507}, issn = {1469-3178}, mesh = {Arabidopsis/*genetics ; *Epigenesis, Genetic ; Mutation ; Retroelements/*genetics ; }, abstract = {Retrotransposons are ubiquitous mobile genetic elements constituting a major part of eukaryotic genomes. Yet, monitoring retrotransposition and subsequent copy number increases in multicellular eukaryotes is intrinsically difficult. By following the transgenerational accumulation of a newly activated retrotransposon EVADE (EVD) in Arabidopsis, we noticed fast expansion of activated elements transmitted through the paternal germ line but suppression when EVD-active copies are maternally inherited. This parent-of-origin effect on EVD proliferation was still observed when gametophytes carried mutations for key epigenetic regulators previously shown to restrict EVD mobility. Therefore, the main mechanism preventing active EVD proliferation seems to act through epigenetic control in sporophytic tissues in the mother plant. In consequence, once activated, this retrotransposon proliferates in plant populations owing to suppressed epigenetic control during paternal transmission. This parental gateway might contribute to the occasional bursts of retrotransposon mobilization deduced from the genome sequences of many plant species.}, } @article {pmid23831049, year = {2013}, author = {Verbeni, M and Sánchez, O and Mollica, E and Siegl-Cachedenier, I and Carleton, A and Guerrero, I and Ruiz i Altaba, A and Soler, J}, title = {Morphogenetic action through flux-limited spreading.}, journal = {Physics of life reviews}, volume = {10}, number = {4}, pages = {457-475}, doi = {10.1016/j.plrev.2013.06.004}, pmid = {23831049}, issn = {1873-1457}, mesh = {Animals ; Drosophila melanogaster/embryology ; Epithelium/metabolism ; Hedgehog Proteins/metabolism ; *Models, Biological ; *Morphogenesis ; Movement ; Neural Tube/cytology/metabolism ; Nonlinear Dynamics ; Signal Transduction ; Wings, Animal/embryology ; }, abstract = {A central question in biology is how secreted morphogens act to induce different cellular responses within a group of cells in a concentration-dependent manner. Modeling morphogenetic output in multicellular systems has so far employed linear diffusion, which is the normal type of diffusion associated with Brownian processes. However, there is evidence that at least some morphogens, such as Hedgehog (Hh) molecules, may not freely diffuse. Moreover, the mathematical analysis of such models necessarily implies unrealistic instantaneous spreading of morphogen molecules, which are derived from the assumptions of Brownian motion in its continuous formulation. A strict mathematical model considering Fick's diffusion law predicts morphogen exposure of the whole tissue at the same time. Such a strict model thus does not describe true biological patterns, even if similar and attractive patterns appear as results of applying such simple model. To eliminate non-biological behaviors from diffusion models we introduce flux-limited spreading (FLS), which implies a restricted velocity for morphogen propagation and a nonlinear mechanism of transport. Using FLS and focusing on intercellular Hh-Gli signaling, we model a morphogen gradient and highlight the propagation velocity of morphogen particles as a new key biological parameter. This model is then applied to the formation and action of the Sonic Hh (Shh) gradient in the vertebrate embryonic neural tube using our experimental data on Hh spreading in heterologous systems together with published data. Unlike linear diffusion models, FLS modeling predicts concentration fronts and the evolution of gradient dynamics and responses over time. In addition to spreading restrictions by extracellular binding partners, we suggest that the constraints imposed by direct bridges of information transfer such as nanotubes or cytonemes underlie FLS. Indeed, we detect and measure morphogen particle velocity in such cell extensions in different systems.}, } @article {pmid23826714, year = {2013}, author = {Ajawatanawong, P and Baldauf, SL}, title = {Evolution of protein indels in plants, animals and fungi.}, journal = {BMC evolutionary biology}, volume = {13}, number = {}, pages = {140}, pmid = {23826714}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; Eukaryota/classification/*genetics ; *Evolution, Molecular ; Fungi/classification/*genetics ; Humans ; *INDEL Mutation ; Molecular Sequence Data ; Phylogeny ; Proteins/*genetics ; Sequence Alignment ; Viridiplantae/classification/*genetics ; }, abstract = {BACKGROUND: Insertions/deletions (indels) in protein sequences are useful as drug targets, protein structure predictors, species diagnostics and evolutionary markers. However there is limited understanding of indel evolutionary patterns. We sought to characterize indel patterns focusing first on the major groups of multicellular eukaryotes.

RESULTS: Comparisons of complete proteomes from a taxonically broad set of primarily Metazoa, Fungi and Viridiplantae yielded 299 substantial (>250aa) universal, single-copy (in-paralog only) proteins, from which 901 simple (present/absent) and 3,806 complex (multistate) indels were extracted. Simple indels are mostly small (1-7aa) with a most frequent size class of 1aa. However, even these simple looking indels show a surprisingly high level of hidden homoplasy (multiple independent origins). Among the apparently homoplasy-free simple indels, we identify 69 potential clade-defining indels (CDIs) that may warrant closer examination. CDIs show a very uneven taxonomic distribution among Viridiplante (13 CDIs), Fungi (40 CDIs), and Metazoa (0 CDIs). An examination of singleton indels shows an excess of insertions over deletions in nearly all examined taxa. This excess averages 2.31 overall, with a maximum observed value of 7.5 fold.

CONCLUSIONS: We find considerable potential for identifying taxon-marker indels using an automated pipeline. However, it appears that simple indels in universal proteins are too rare and homoplasy-rich to be used for pure indel-based phylogeny. The excess of insertions over deletions seen in nearly every genome and major group examined maybe useful in defining more realistic gap penalties for sequence alignment. This bias also suggests that insertions in highly conserved proteins experience less purifying selection than do deletions.}, } @article {pmid23817070, year = {2013}, author = {Gauthier, NP and Soufi, B and Walkowicz, WE and Pedicord, VA and Mavrakis, KJ and Macek, B and Gin, DY and Sander, C and Miller, ML}, title = {Cell-selective labeling using amino acid precursors for proteomic studies of multicellular environments.}, journal = {Nature methods}, volume = {10}, number = {8}, pages = {768-773}, pmid = {23817070}, issn = {1548-7105}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; U54 CA148967/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Cell Line ; Coculture Techniques/methods ; Humans ; Isotope Labeling/methods ; Lysine/*metabolism ; Mice ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis ; Organisms, Genetically Modified ; Proteome/*biosynthesis/genetics ; Proteomics/*methods ; RNA, Messenger/chemistry/genetics ; Sequence Analysis, DNA ; Tandem Mass Spectrometry ; }, abstract = {We report a technique to selectively and continuously label the proteomes of individual cell types in coculture, named cell type-specific labeling using amino acid precursors (CTAP). Through transgenic expression of exogenous amino acid biosynthesis enzymes, vertebrate cells overcome their dependence on supplemented essential amino acids and can be selectively labeled through metabolic incorporation of amino acids produced from heavy isotope-labeled precursors. When testing CTAP in several human and mouse cell lines, we could differentially label the proteomes of distinct cell populations in coculture and determine the relative expression of proteins by quantitative mass spectrometry. In addition, using CTAP we identified the cell of origin of extracellular proteins secreted from cells in coculture. We believe that this method, which allows linking of proteins to their cell source, will be useful in studies of cell-cell communication and potentially for discovery of biomarkers.}, } @article {pmid23816391, year = {2013}, author = {Strand, MR and Burke, GR}, title = {Polydnavirus-wasp associations: evolution, genome organization, and function.}, journal = {Current opinion in virology}, volume = {3}, number = {5}, pages = {587-594}, doi = {10.1016/j.coviro.2013.06.004}, pmid = {23816391}, issn = {1879-6265}, support = {F32 AI096552/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; *Genome, Viral ; Polydnaviridae/*genetics/physiology ; Proviruses/*genetics/physiology ; Wasps/*virology ; }, abstract = {Viruses replicate to produce virions that transfer the viral genome among hosts, while endogenous viral elements (EVEs) are DNA sequences derived from viruses that integrate into the germline of multicellular organisms and are thereafter inherited like host alleles. Viruses in the family Polydnaviridae are specifically associated with insects called parasitoid wasps and exhibit many traits associated with other viruses. Polydnavirus genomes also persist as EVEs. In this short review we discuss polydnavirus evolution, compare polydnaviruses to other known EVEs of ancient origin, and examine some of the functional similarities polydnaviruses share with phage-like gene transfer agents (GTAs) from prokaryotes.}, } @article {pmid23809699, year = {2013}, author = {Raff, EC and Andrews, ME and Turner, FR and Toh, E and Nelson, DE and Raff, RA}, title = {Contingent interactions among biofilm-forming bacteria determine preservation or decay in the first steps toward fossilization of marine embryos.}, journal = {Evolution & development}, volume = {15}, number = {4}, pages = {243-256}, doi = {10.1111/ede.12028}, pmid = {23809699}, issn = {1525-142X}, mesh = {Aerobiosis ; Anaerobiosis ; Animals ; Artemia/physiology ; Bacteria/*metabolism ; Bacterial Physiological Phenomena ; *Biofilms ; Biological Evolution ; Cytoplasm/metabolism ; *Fossils ; Gammaproteobacteria/metabolism ; Larva ; Lipids/analysis ; Sea Urchins/physiology ; Seawater/*microbiology ; Water Microbiology ; }, abstract = {Fossils of soft tissues provide important records of early animals and embryos, and there is substantial evidence for a role for microbes in soft tissue fossilization. We are investigating the initial events in interactions of bacteria with freshly dead tissue, using marine embryos as a model system. We previously found that microbial invasion can stabilize embryo tissue that would otherwise disintegrate in hours or days by generating a bacterial pseudomorph, a three dimensional biofilm that both replaces the tissue and replicates its morphology. In this study, we sampled seawater at different times and places near Sydney, Australia, and determined the range and frequency of different taphonomic outcomes. Although destruction was most common, bacteria in 35% of seawater samples yielded morphology‐preserving biofilms. We could replicate the taphonomic pathways seen with seawater bacterial communities using single cultured strains of marine gammaproteobacteria. Each given species reproducibly generated a consistent taphonomic outcome and we identified species that yielded each of the distinct pathways produced by seawater bacterial communities. Once formed,bacterial pseudomorphs are stable for over a year and resist attack by other bacteria and destruction by proteases and other lytic enzymes. Competition studies showed that the initial action of a pseudomorphing strain can be blocked by a strain that destroys tissues. Thus embryo preservation in nature may depend on contingent interactions among bacterial species that determine if pseudomorphing occurs.We used Artemia nauplius larvae to show that bacterial biofilm replacement of tissue is not restricted to embryos, but is relevant for preservation of small multicellular organisms. We present a model for bacterial self‐assembly of large‐scale three‐dimensional tissue pseudomorphs, based on smallscaleinteractions among individual bacterial cells to form local biofilms at structural boundaries within the tissue. Localbiofilms then conjoin to generate the pseudomorph.}, } @article {pmid23808329, year = {2013}, author = {Bosch, TC}, title = {Cnidarian-microbe interactions and the origin of innate immunity in metazoans.}, journal = {Annual review of microbiology}, volume = {67}, number = {}, pages = {499-518}, doi = {10.1146/annurev-micro-092412-155626}, pmid = {23808329}, issn = {1545-3251}, mesh = {Animals ; Bacteria/growth & development ; Cnidaria/genetics/*immunology/*microbiology ; Humans ; *Immunity, Innate ; *Microbiota ; Receptors, Pattern Recognition/genetics/immunology ; Symbiosis ; }, abstract = {Most epithelia in animals are colonized by microbial communities. These resident microbes influence fitness and thus ecologically important traits of their hosts, ultimately forming a metaorganism consisting of a multicellular host and a community of associated microorganisms. Recent discoveries in the cnidarian Hydra show that components of the innate immune system as well as transcriptional regulators of stem cells are involved in maintaining homeostasis between animals and their resident microbiota. Here I argue that components of the innate immune system with its host-specific antimicrobial peptides and a rich repertoire of pattern recognition receptors evolved in early-branching metazoans because of the need to control the resident beneficial microbes, not because of invasive pathogens. I also propose a mutual intertwinement between the stem cell regulatory machinery of the host and the resident microbiota composition, such that disturbances in one trigger a restructuring and resetting of the other.}, } @article {pmid23782883, year = {2013}, author = {Romeralo, M and Skiba, A and Gonzalez-Voyer, A and Schilde, C and Lawal, H and Kedziora, S and Cavender, JC and Glöckner, G and Urushihara, H and Schaap, P}, title = {Analysis of phenotypic evolution in Dictyostelia highlights developmental plasticity as a likely consequence of colonial multicellularity.}, journal = {Proceedings. Biological sciences}, volume = {280}, number = {1764}, pages = {20130976}, pmid = {23782883}, issn = {1471-2954}, support = {090276//Wellcome Trust/United Kingdom ; BB/D013453/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/E016308/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/G020426/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Chemotactic Factors/physiology ; Cyclic AMP/analogs & derivatives/metabolism/pharmacology ; Dictyosteliida/*cytology/drug effects/*physiology ; Multifactorial Inheritance ; Phenotype ; Phototropism ; Phylogeny ; Proteins/genetics ; Thionucleotides/pharmacology ; }, abstract = {Colony formation was the first step towards evolution of multicellularity in many macroscopic organisms. Dictyostelid social amoebas have used this strategy for over 600 Myr to form fruiting structures of increasing complexity. To understand in which order multicellular complexity evolved, we measured 24 phenotypic characters over 99 dictyostelid species. Using phylogenetic comparative methods, we show that the last common ancestor (LCA) of Dictyostelia probably erected small fruiting structures directly from aggregates. It secreted cAMP to coordinate fruiting body morphogenesis, and another compound to mediate aggregation. This phenotype persisted up to the LCAs of three of the four major groups of Dictyostelia. The group 4 LCA co-opted cAMP for aggregation and evolved much larger fruiting structures. However, it lost encystation, the survival strategy of solitary amoebas that is retained by many species in groups 1-3. Large structures, phototropism and a migrating intermediate 'slug' stage coevolved as evolutionary novelties within most groups. Overall, dictyostelids show considerable plasticity in the size and shape of multicellular structures, both within and between species. This probably reflects constraints placed by colonial life on developmental control mechanisms, which, depending on local cell density, need to direct from 10 to a million cells into forming a functional fructification.}, } @article {pmid23776247, year = {2013}, author = {Shih, PM and Matzke, NJ}, title = {Primary endosymbiosis events date to the later Proterozoic with cross-calibrated phylogenetic dating of duplicated ATPase proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {30}, pages = {12355-12360}, pmid = {23776247}, issn = {1091-6490}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Adenosine Triphosphatases/classification/*metabolism ; Calibration ; *Phylogeny ; *Symbiosis ; }, abstract = {Chloroplasts and mitochondria descended from bacterial ancestors, but the dating of these primary endosymbiosis events remains very uncertain, despite their importance for our understanding of the evolution of both bacteria and eukaryotes. All phylogenetic dating in the Proterozoic and before is difficult: Significant debates surround potential fossil calibration points based on the interpretation of the Precambrian microbial fossil record, and strict molecular clock methods cannot be expected to yield accurate dates over such vast timescales because of strong heterogeneity in rates. Even with more sophisticated relaxed-clock analyses, nodes that are distant from fossil calibrations will have a very high uncertainty in dating. However, endosymbiosis events and gene duplications provide some additional information that has never been exploited in dating; namely, that certain nodes on a gene tree must represent the same events, and thus must have the same or very similar dates, even if the exact date is uncertain. We devised techniques to exploit this information: cross-calibration, in which node date calibrations are reused across a phylogeny, and cross-bracing, in which node date calibrations are formally linked in a hierarchical Bayesian model. We apply these methods to proteins with ancient duplications that have remained associated and originated from plastid and mitochondrial endosymbionts: the α and β subunits of ATP synthase and its relatives, and the elongation factor thermo unstable. The methods yield reductions in dating uncertainty of 14-26% while only using date calibrations derived from phylogenetically unambiguous Phanerozoic fossils of multicellular plants and animals. Our results suggest that primary plastid endosymbiosis occurred ∼900 Mya and mitochondrial endosymbiosis occurred ∼1,200 Mya.}, } @article {pmid23767751, year = {2013}, author = {Roper, M and Dayel, MJ and Pepper, RE and Koehl, MA}, title = {Cooperatively generated stresslet flows supply fresh fluid to multicellular choanoflagellate colonies.}, journal = {Physical review letters}, volume = {110}, number = {22}, pages = {228104}, doi = {10.1103/PhysRevLett.110.228104}, pmid = {23767751}, issn = {1079-7114}, mesh = {Choanoflagellata/chemistry/*physiology ; Flagella/chemistry/*physiology ; Hydrodynamics ; *Models, Biological ; Stress, Physiological ; Swimming ; Viscosity ; }, abstract = {The flagellated protozoan Salpingoeca rosetta is one of the closest relatives of multicellular animals. Unicellular S. rosetta can be induced to form multicellular colonies, but colonies swim more slowly than individual cells so the advantages conferred by colony formation are uncertain. Here we use theoretical models to show that hydrodynamic cooperation between cells can increase the fluid supply to the colony, an important predictor of feeding rate. Our results suggest that hydrodynamic benefits may have been an important selective factor in the evolution of early multicellular animals.}, } @article {pmid23760641, year = {2013}, author = {Shirokawa, Y and Shimada, M}, title = {Sex allocation pattern of the diatom Cyclotella meneghiniana.}, journal = {Proceedings. Biological sciences}, volume = {280}, number = {1761}, pages = {20130503}, pmid = {23760641}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; Cell Count ; Cell Lineage ; Cell Size ; Diatoms/*cytology/*physiology ; Female ; Game Theory ; Male ; Microfluidic Analytical Techniques ; Reproduction ; Sex Differentiation ; *Sex Ratio ; }, abstract = {Sex allocation is one of the most successful applications of evolutionary game theory. This theory has usually been applied to multicellular organisms; however, conditional sex allocation in unicellular organisms remains an unexplored field of research. Observations at the cellular level are indispensable for an understanding of the phenotypic sex allocation strategy among individuals within clonal unicellular organisms. The diatom Cyclotella meneghiniana, in which the sexes are generated from vegetative cells, is suitable for investigating effects of phenotypic plasticity factors on sex allocation while excluding genetic differences. We designed a microfluidic system that allowed us to trace the fate of individual cells. Sex allocation by individual mother cells was affected by cell lineage, cell size and cell density. Sibling cell pairs tended to differentiate into the same fates (split sex ratio). We found a significant negative correlation between the cell area of the mother cell and sex ratio of the two sibling cells. The male-biased sex ratio declined with higher local cell population density, supporting the fertility insurance hypothesis. Our results characterize multiple non-genetic factors that affect the phenotypic single cell-level sex allocation. Sex allocation in diatoms may provide a model system for testing evolutionary game theory in unicellular organisms.}, } @article {pmid23754817, year = {2013}, author = {Blackstone, NW}, title = {Why did eukaryotes evolve only once? Genetic and energetic aspects of conflict and conflict mediation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {368}, number = {1622}, pages = {20120266}, pmid = {23754817}, issn = {1471-2970}, mesh = {*Biological Evolution ; *Energy Metabolism ; Eukaryota/*genetics/*physiology ; Genetic Variation ; Genome ; Mitochondria ; }, abstract = {According to multi-level theory, evolutionary transitions require mediating conflicts between lower-level units in favour of the higher-level unit. By this view, the origin of eukaryotes and the origin of multicellularity would seem largely equivalent. Yet, eukaryotes evolved only once in the history of life, whereas multicellular eukaryotes have evolved many times. Examining conflicts between evolutionary units and mechanisms that mediate these conflicts can illuminate these differences. Energy-converting endosymbionts that allow eukaryotes to transcend surface-to-volume constraints also can allocate energy into their own selfish replication. This principal conflict in the origin of eukaryotes can be mediated by genetic or energetic mechanisms. Genome transfer diminishes the heritable variation of the symbiont, but requires the de novo evolution of the protein-import apparatus and was opposed by selection for selfish symbionts. By contrast, metabolic signalling is a shared primitive feature of all cells. Redox state of the cytosol is an emergent feature that cannot be subverted by an individual symbiont. Hypothetical scenarios illustrate how metabolic regulation may have mediated the conflicts inherent at different stages in the origin of eukaryotes. Aspects of metabolic regulation may have subsequently been coopted from within-cell to between-cell pathways, allowing multicellularity to emerge repeatedly.}, } @article {pmid23748924, year = {2013}, author = {Kent, CF and Zayed, A}, title = {Evolution of recombination and genome structure in eusocial insects.}, journal = {Communicative & integrative biology}, volume = {6}, number = {2}, pages = {e22919}, pmid = {23748924}, issn = {1942-0889}, abstract = {Eusocial Hymenoptera, such as the European honey bee, Apis mellifera, have the highest recombination rates of multicellular animals.(1) Recently, we showed(2) that a side-effect of recombination in the honey bee, GC biased gene conversion (bGC), helps maintain the unusual bimodal GC-content distribution of the bee genome by increasing GC-content in high recombination areas while low recombination areas are losing GC-content because of biased AT mutations and low rates of bGC. Although the very high recombination rate of A. mellifera makes GC-content evolution easier to study, the pattern is consistent with results found in many other species including mammals and yeast.(3) Also consistent across phyla is the association of higher genetic diversity and divergence with high GC and high recombination areas.(4) (,) (5) Finally, we showed that genes overexpressed in the brains of workers cluster in GC-rich genomic areas with the highest rates of recombination and molecular evolution.(2) In this Addendum we present a conceptual model of how eusociality and high recombination rates may co-evolve.}, } @article {pmid23747737, year = {2013}, author = {Häcker, G}, title = {Is there, and should there be, apoptosis in bacteria?.}, journal = {Microbes and infection}, volume = {15}, number = {8-9}, pages = {640-644}, doi = {10.1016/j.micinf.2013.05.005}, pmid = {23747737}, issn = {1769-714X}, mesh = {*Apoptosis ; Bacteria/cytology ; *Bacterial Physiological Phenomena ; }, abstract = {Apoptosis is a well-studied form of cell death in metazoans, where it has a clear role during the life of the (multicellular) animal. Some situations of cell death in unicellular eukaryotes (protozoa and yeast) have also been referred to as apoptosis. In recent years apoptosis has further been identified in bacteria several times. As a bacterial response to external stimuli, apoptosis could be important not only for the bacteria but also to the host. Here I will discuss why I believe that the term apoptosis should be avoided for these situations in bacteria, no matter how interesting the molecular background or how biologically important the underlying mechanism may be.}, } @article {pmid23746639, year = {2013}, author = {Fisher, RM and Cornwallis, CK and West, SA}, title = {Group formation, relatedness, and the evolution of multicellularity.}, journal = {Current biology : CB}, volume = {23}, number = {12}, pages = {1120-1125}, doi = {10.1016/j.cub.2013.05.004}, pmid = {23746639}, issn = {1879-0445}, mesh = {*Biological Evolution ; Eukaryotic Cells/*physiology ; *Evolution, Molecular ; Models, Genetic ; Selection, Genetic ; }, abstract = {The evolution of multicellular organisms represents one of approximately eight major evolutionary transitions that have occurred on earth. The major challenge raised by this transition is to explain why single cells should join together and become mutually dependent, in a way that leads to a more complex multicellular life form that can only replicate as a whole. It has been argued that a high genetic relatedness (r) between cells played a pivotal role in the evolutionary transition from single-celled to multicellular organisms, because it leads to reduced conflict and an alignment of interests between cells. We tested this hypothesis with a comparative study, comparing the form of multicellularity in species where groups are clonal (r = 1) to species where groups are potentially nonclonal (r ≤ 1). We found that species with clonal group formation were more likely to have undergone the major evolutionary transition to obligate multicellularity and had more cell types, a higher likelihood of sterile cells, and a trend toward higher numbers of cells in a group. More generally, our results unify the role of group formation and genetic relatedness across multiple evolutionary transitions and provide an unmistakable footprint of how natural selection has shaped the evolution of life.}, } @article {pmid23738841, year = {2013}, author = {Whitehead, MP and Hooley, P and W Brown, MR}, title = {Horizontal transfer of bacterial polyphosphate kinases to eukaryotes: implications for the ice age and land colonisation.}, journal = {BMC research notes}, volume = {6}, number = {}, pages = {221}, pmid = {23738841}, issn = {1756-0500}, mesh = {Amino Acid Sequence ; Bacteria/*enzymology ; *Gene Transfer, Horizontal ; *Ice ; Molecular Sequence Data ; Phosphotransferases (Phosphate Group Acceptor)/chemistry/genetics/*metabolism ; Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {BACKGROUND: Studies of online database(s) showed that convincing examples of eukaryote PPKs derived from bacteria type PPK1 and PPK2 enzymes are rare and currently confined to a few simple eukaryotes. These enzymes probably represent several separate horizontal transfer events. Retention of such sequences may be an advantage for tolerance to stresses such as desiccation or nutrient depletion for simple eukaryotes that lack more sophisticated adaptations available to multicellular organisms. We propose that the acquisition of encoding sequences for these enzymes by horizontal transfer enhanced the ability of early plants to colonise the land. The improved ability to sequester and release inorganic phosphate for carbon fixation by photosynthetic algae in the ocean may have accelerated or even triggered global glaciation events. There is some evidence for DNA sequences encoding PPKs in a wider range of eukaryotes, notably some invertebrates, though it is unclear that these represent functional genes.Polyphosphate (poly P) is found in all cells, carrying out a wide range of essential roles. Studied mainly in prokaryotes, the enzymes responsible for synthesis of poly P in eukaryotes (polyphosphate kinases PPKs) are not well understood. The best characterised enzyme from bacteria known to catalyse the formation of high molecular weight polyphosphate from ATP is PPK1 which shows some structural similarity to phospholipase D. A second bacterial PPK (PPK2) resembles thymidylate kinase. Recent reports have suggested a widespread distribution of these bacteria type enzymes in eukaryotes.

RESULTS: On - line databases show evidence for the presence of genes encoding PPK1 in only a limited number of eukaryotes. These include the photosynthetic eukaryotes Ostreococcus tauri, O. lucimarinus, Porphyra yezoensis, Cyanidioschyzon merolae and the moss Physcomitrella patens, as well as the amoeboid symbiont Capsaspora owczarzaki and the non-photosynthetic eukaryotes Dictyostelium (3 species), Polysphondylium pallidum and Thecamonas trahens. A second bacterial PPK (PPK2) is found in just two eukaryotes (O. tauri and the sea anemone Nematostella vectensis). There is some evidence for PPK1 and PPK2 encoding sequences in other eukaryotes but some of these may be artefacts of bacterial contamination of gene libraries.

CONCLUSIONS: Evidence for the possible origins of these eukaryote PPK1s and PPK2s and potential prokaryote donors via horizontal gene transfer is presented. The selective advantage of acquiring and maintaining a prokaryote PPK in a eukaryote is proposed to enhance stress tolerance in a changing environment related to the capture and metabolism of inorganic phosphate compounds. Bacterial PPKs may also have enhanced the abilities of marine phytoplankton to sequester phosphate, hence accelerating global carbon fixation.}, } @article {pmid23736899, year = {2013}, author = {Rothballer, A and Kutay, U}, title = {The diverse functional LINCs of the nuclear envelope to the cytoskeleton and chromatin.}, journal = {Chromosoma}, volume = {122}, number = {5}, pages = {415-429}, pmid = {23736899}, issn = {1432-0886}, mesh = {Chromatin/*genetics ; Cytoskeleton/*genetics ; Humans ; Membrane Proteins/genetics/metabolism ; Microtubules/genetics ; Nuclear Envelope/*genetics ; Nuclear Matrix/genetics ; Protein Structure, Tertiary ; }, abstract = {The nuclear envelope (NE) is connected to the different types of cytoskeletal elements by linker of nucleoskeleton and cytoskeleton (LINC) complexes. LINC complexes exist from yeast to humans, and have preserved their general architecture throughout evolution. They are composed of SUN and KASH domain proteins of the inner and the outer nuclear membrane, respectively. These SUN-KASH bridges are used for the transmission of forces across the NE and support diverse biological processes. Here, we review the function of SUN and KASH domain proteins in various unicellular and multicellular species. Specifically, we discuss their influence on nuclear morphology and cytoskeletal organization. Further, emphasis is given on the role of LINC complexes in nuclear anchorage and migration as well as in genome organization.}, } @article {pmid23735467, year = {2013}, author = {Libby, E and B Rainey, P}, title = {A conceptual framework for the evolutionary origins of multicellularity.}, journal = {Physical biology}, volume = {10}, number = {3}, pages = {035001}, doi = {10.1088/1478-3975/10/3/035001}, pmid = {23735467}, issn = {1478-3975}, mesh = {Animals ; *Biological Evolution ; Cell Biology ; Evolution, Molecular ; Humans ; Models, Genetic ; Selection, Genetic ; }, abstract = {The evolution of multicellular organisms from unicellular counterparts involved a transition in Darwinian individuality from single cells to groups. A particular challenge is to understand the nature of the earliest groups, the causes of their evolution, and the opportunities for emergence of Darwinian properties. Here we outline a conceptual framework based on a logical set of possible pathways for evolution of the simplest self-replicating groups. Central to these pathways is the recognition of a finite number of routes by which genetic information can be transmitted between individual cells and groups. We describe the form and organization of each primordial group state and consider factors affecting persistence and evolution of the nascent multicellular forms. Implications arising from our conceptual framework become apparent when attempting to partition fitness effects at individual and group levels. These are discussed with reference to the evolutionary emergence of individuality and its manifestation in extant multicellular life-including those of marginal Darwinian status.}, } @article {pmid23734264, year = {2013}, author = {Wang, L and Mao, Y and Kong, F and Li, G and Ma, F and Zhang, B and Sun, P and Bi, G and Zhang, F and Xue, H and Cao, M}, title = {Complete sequence and analysis of plastid genomes of two economically important red algae: Pyropia haitanensis and Pyropia yezoensis.}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e65902}, pmid = {23734264}, issn = {1932-6203}, mesh = {Chloroplast Proteins/classification/*genetics ; Gene Order ; Genome, Plastid/*genetics ; Molecular Sequence Data ; Phylogeny ; Rhodophyta/classification/*genetics ; Sequence Analysis, DNA/*methods ; Species Specificity ; }, abstract = {BACKGROUND: Pyropia haitanensis and P. yezoensis are two economically important marine crops that are also considered to be research models to study the physiological ecology of intertidal seaweed communities, evolutionary biology of plastids, and the origins of sexual reproduction. This plastid genome information will facilitate study of breeding, population genetics and phylogenetics.

PRINCIPAL FINDINGS: We have fully sequenced using next-generation sequencing the circular plastid genomes of P. hatanensis (195,597 bp) and P. yezoensis (191,975 bp), the largest of all the plastid genomes of the red lineage sequenced to date. Organization and gene contents of the two plastids were similar, with 211-213 protein-coding genes (including 29-31 unknown-function ORFs), 37 tRNA genes, and 6 ribosomal RNA genes, suggesting a largest coding capacity in the red lineage. In each genome, 14 protein genes overlapped and no interrupted genes were found, indicating a high degree of genomic condensation. Pyropia maintain an ancient gene content and conserved gene clusters in their plastid genomes, containing nearly complete repertoires of the plastid genes known in photosynthetic eukaryotes. Similarity analysis based on the whole plastid genome sequences showed the distance between P. haitanensis and P. yezoensis (0.146) was much smaller than that of Porphyra purpurea and P. haitanensis (0.250), and P. yezoensis (0.251); this supports re-grouping the two species in a resurrected genus Pyropia while maintaining P. purpurea in genus Porphyra. Phylogenetic analysis supports a sister relationship between Bangiophyceae and Florideophyceae, though precise phylogenetic relationships between multicellular red alage and chromists were not fully resolved.

CONCLUSIONS: These results indicate that Pyropia have compact plastid genomes. Large coding capacity and long intergenic regions contribute to the size of the largest plastid genomes reported for the red lineage. Possessing the largest coding capacity and ancient gene content yet found reveal that Pyropia are more primitive multicellular red algae.}, } @article {pmid23732772, year = {2013}, author = {Martinez, CA and Barr, KA and Kim, AR and Reinitz, J}, title = {A synthetic biology approach to the development of transcriptional regulatory models and custom enhancer design.}, journal = {Methods (San Diego, Calif.)}, volume = {62}, number = {1}, pages = {91-98}, pmid = {23732772}, issn = {1095-9130}, support = {P50 GM081892/GM/NIGMS NIH HHS/United States ; R01 RR07801/RR/NCRR NIH HHS/United States ; R01 GM070444/GM/NIGMS NIH HHS/United States ; R01 GM70444/GM/NIGMS NIH HHS/United States ; R01 RR007801/RR/NCRR NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; Binding Sites ; Body Patterning/genetics ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/embryology/*genetics/metabolism ; Embryo, Nonmammalian/cytology/*metabolism/ultrastructure ; *Enhancer Elements, Genetic ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Homeodomain Proteins/genetics/metabolism ; Image Processing, Computer-Assisted/statistics & numerical data ; In Situ Hybridization ; *Models, Genetic ; Protein Binding ; Synthetic Biology/*methods ; Transcription Factors/genetics/metabolism ; Transcription, Genetic ; }, abstract = {Synthetic biology offers novel opportunities for elucidating transcriptional regulatory mechanisms and enhancer logic. Complex cis-regulatory sequences--like the ones driving expression of the Drosophila even-skipped gene--have proven difficult to design from existing knowledge, presumably due to the large number of protein-protein interactions needed to drive the correct expression patterns of genes in multicellular organisms. This work discusses two novel computational methods for the custom design of enhancers that employ a sophisticated, empirically validated transcriptional model, optimization algorithms, and synthetic biology. These synthetic elements have both utilitarian and academic value, including improving existing regulatory models as well as evolutionary questions. The first method involves the use of simulated annealing to explore the sequence space for synthetic enhancers whose expression output fit a given search criterion. The second method uses a novel optimization algorithm to find functionally accessible pathways between two enhancer sequences. These paths describe a set of mutations wherein the predicted expression pattern does not significantly vary at any point along the path. Both methods rely on a predictive mathematical framework that maps the enhancer sequence space to functional output.}, } @article {pmid23730752, year = {2013}, author = {Ratcliff, WC and Pentz, JT and Travisano, M}, title = {Tempo and mode of multicellular adaptation in experimentally evolved Saccharomyces cerevisiae.}, journal = {Evolution; international journal of organic evolution}, volume = {67}, number = {6}, pages = {1573-1581}, doi = {10.1111/evo.12101}, pmid = {23730752}, issn = {1558-5646}, mesh = {Adaptation, Biological/*genetics ; Evolution, Molecular ; Saccharomyces cerevisiae/cytology/*genetics ; *Selection, Genetic ; Time Factors ; }, abstract = {Multicellular complexity is a central topic in biology, but the evolutionary processes underlying its origin are difficult to study and remain poorly understood. Here we use experimental evolution to investigate the tempo and mode of multicellular adaptation during a de novo evolutionary transition to multicellularity. Multicelled "snowflake" yeast evolved from a unicellular ancestor after 7 days of selection for faster settling through liquid media. Over the next 220 days, snowflake yeast evolved to settle 44% more quickly. Throughout the experiment the clusters evolved faster settling by three distinct modes. The number of cells per cluster increased from a mean of 42 cells after 7 days of selection to 114 cells after 227 days. Between days 28 and 65, larger clusters evolved via a twofold increase in the mass of individual cells. By day 227, snowflake yeast evolved to form more hydrodynamic clusters that settle more quickly for their size than ancestral strains. The timing and nature of adaptation in our experiment suggests that costs associated with large cluster size favor novel multicellular adaptations, increasing organismal complexity.}, } @article {pmid23730751, year = {2013}, author = {Simon, B and Fletcher, JA and Doebeli, M}, title = {Towards a general theory of group selection.}, journal = {Evolution; international journal of organic evolution}, volume = {67}, number = {6}, pages = {1561-1572}, doi = {10.1111/j.1558-5646.2012.01835.x}, pmid = {23730751}, issn = {1558-5646}, mesh = {Animals ; Evolution, Molecular ; Markov Chains ; *Models, Genetic ; Population/genetics ; *Selection, Genetic ; }, abstract = {The longstanding debate about the importance of group (multilevel) selection suffers from a lack of formal models that describe explicit selection events at multiple levels. Here, we describe a general class of models for two-level evolutionary processes which include birth and death events at both levels. The models incorporate the state-dependent rates at which these events occur. The models come in two closely related forms: (1) a continuous-time Markov chain, and (2) a partial differential equation (PDE) derived from (1) by taking a limit. We argue that the mathematical structure of this PDE is the same for all models of two-level population processes, regardless of the kinds of events featured in the model. The mathematical structure of the PDE allows for a simple and unambiguous way to distinguish between individual- and group-level events in any two-level population model. This distinction, in turn, suggests a new and intuitively appealing way to define group selection in terms of the effects of group-level events. We illustrate our theory of group selection by applying it to models of the evolution of cooperation and the evolution of simple multicellular organisms, and then demonstrate that this kind of group selection is not mathematically equivalent to individual-level (kin) selection.}, } @article {pmid23728794, year = {2013}, author = {Odon, V and Luke, GA and Roulston, C and de Felipe, P and Ruan, L and Escuin-Ordinas, H and Brown, JD and Ryan, MD and Sukhodub, A}, title = {APE-type non-LTR retrotransposons of multicellular organisms encode virus-like 2A oligopeptide sequences, which mediate translational recoding during protein synthesis.}, journal = {Molecular biology and evolution}, volume = {30}, number = {8}, pages = {1955-1965}, pmid = {23728794}, issn = {1537-1719}, support = {G0901002/MRC_/Medical Research Council/United Kingdom ; BB/E010709/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/E009093/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; C20035/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/H007849/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Genome, Protozoan ; Molecular Sequence Data ; Oligopeptides/chemistry/*genetics ; Open Reading Frames ; Phylogeny ; Protein Biosynthesis/*physiology ; Retroelements/*genetics ; Sequence Alignment ; Trypanosoma/classification/*genetics/*metabolism ; }, abstract = {2A oligopeptide sequences ("2As") mediate a cotranslational recoding event termed "ribosome skipping." Previously we demonstrated the activity of 2As (and "2A-like sequences") within a wide range of animal RNA virus genomes and non-long terminal repeat retrotransposons (non-LTRs) in the genomes of the unicellular organisms Trypanosoma brucei (Ingi) and T. cruzi (L1Tc). Here, we report the presence of 2A-like sequences in the genomes of a wide range of multicellular organisms and, as in the trypanosome genomes, within non-LTR retrotransposons (non-LTRs)-clustering in the Rex1, Crack, L2, L2A, and CR1 clades, in addition to Ingi. These 2A-like sequences were tested for translational recoding activity, and highly active sequences were found within the Rex1, L2, CR1, and Ingi clades. The presence of 2A-like sequences within non-LTRs may not only represent a method of controlling protein biogenesis but also shows some correlation with such apurinic/apyrimidinic DNA endonuclease-type non-LTRs encoding one, rather than two, open reading frames (ORFs). Interestingly, such non-LTRs cluster with closely related elements lacking 2A-like recoding elements but retaining ORF1. Taken together, these observations suggest that acquisition of 2A-like translational recoding sequences may have played a role in the evolution of these elements.}, } @article {pmid23724825, year = {2013}, author = {Baugher, JD and Baugher, BD and Shirley, MD and Pevsner, J}, title = {Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method.}, journal = {BMC genomics}, volume = {14}, number = {}, pages = {367}, pmid = {23724825}, issn = {1471-2164}, support = {R21 DE 016930/DE/NIDCR NIH HHS/United States ; U01-HG-004446/HG/NHGRI NIH HHS/United States ; R21-DE-013707/DE/NIDCR NIH HHS/United States ; R01-DE-012472/DE/NIDCR NIH HHS/United States ; R01 DE016148/DE/NIDCR NIH HHS/United States ; R01-DE-016148/DE/NIDCR NIH HHS/United States ; U01 DE 018993/DE/NIDCR NIH HHS/United States ; /ImNIH/Intramural NIH HHS/United States ; R01-DE-013939/DE/NIDCR NIH HHS/United States ; R01-DE-09886/DE/NIDCR NIH HHS/United States ; R37-DE-08559/DE/NIDCR NIH HHS/United States ; 1U24MH081810/MH/NIMH NIH HHS/United States ; R01-DE-014677/DE/NIDCR NIH HHS/United States ; P50-DE-016215/DE/NIDCR NIH HHS/United States ; R01-DE-014581/DE/NIDCR NIH HHS/United States ; }, mesh = {Algorithms ; *Chromosome Aberrations ; Computational Biology/*methods ; Internet ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide ; Software ; }, abstract = {BACKGROUND: Mosaic somatic alterations are present in all multi-cellular organisms, but the physiological effects of low-level mosaicism are largely unknown. Most mosaic alterations remain undetectable with current analytical approaches, although the presence of such alterations is increasingly implicated as causative for disease.

RESULTS: Here, we present the Parent-of-Origin-based Detection (POD) method for chromosomal abnormality detection in trio-based SNP microarray data. Our software implementation, triPOD, was benchmarked using a simulated dataset, outperformed comparable software for sensitivity of abnormality detection, and displayed substantial improvement in the detection of low-level mosaicism while maintaining comparable specificity. Examples of low-level mosaic abnormalities from a large autism dataset demonstrate the benefits of the increased sensitivity provided by triPOD. The triPOD analyses showed robustness across multiple types of Illumina microarray chips. Two large, clinically-relevant datasets were characterized and compared.

CONCLUSIONS: Our method and software provide a significant advancement in the ability to detect low-level mosaic abnormalities, thereby opening new avenues for research into the implications of mosaicism in pathogenic and non-pathogenic processes.}, } @article {pmid23724074, year = {2013}, author = {Zwart, MP and Tromas, N and Elena, SF}, title = {Model-selection-based approach for calculating cellular multiplicity of infection during virus colonization of multi-cellular hosts.}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e64657}, pmid = {23724074}, issn = {1932-6203}, mesh = {Caulimovirus/*physiology ; Host-Pathogen Interactions/*physiology ; *Models, Theoretical ; Plants/*virology ; Poisson Distribution ; Tobacco Mosaic Virus/*physiology ; Virus Replication/*physiology ; }, abstract = {The cellular multiplicity of infection (MOI) is a key parameter for describing the interactions between virions and cells, predicting the dynamics of mixed-genotype infections, and understanding virus evolution. Two recent studies have reported in vivo MOI estimates for Tobacco mosaic virus (TMV) and Cauliflower mosaic virus (CaMV), using sophisticated approaches to measure the distribution of two virus variants over host cells. Although the experimental approaches were similar, the studies employed different definitions of MOI and estimation methods. Here, new model-selection-based methods for calculating MOI were developed. Seven alternative models for predicting MOI were formulated that incorporate an increasing number of parameters. For both datasets the best-supported model included spatial segregation of virus variants over time, and to a lesser extent aggregation of virus-infected cells was also implicated. Three methods for MOI estimation were then compared: the two previously reported methods and the best-supported model. For CaMV data, all three methods gave comparable results. For TMV data, the previously reported methods both predicted low MOI values (range: 1.04-1.23) over time, whereas the best-supported model predicted a wider range of MOI values (range: 1.01-2.10) and an increase in MOI over time. Model selection can therefore identify suitable alternative MOI models and suggest key mechanisms affecting the frequency of coinfected cells. For the TMV data, this leads to appreciable differences in estimated MOI values.}, } @article {pmid23721178, year = {2013}, author = {Nardmann, J and Werr, W}, title = {Symplesiomorphies in the WUSCHEL clade suggest that the last common ancestor of seed plants contained at least four independent stem cell niches.}, journal = {The New phytologist}, volume = {199}, number = {4}, pages = {1081-1092}, doi = {10.1111/nph.12343}, pmid = {23721178}, issn = {1469-8137}, mesh = {Gene Expression Regulation, Plant ; Homeodomain Proteins/*metabolism ; Meristem/metabolism ; Phylogeny ; Plant Leaves/metabolism ; Plant Proteins/*metabolism ; Plant Vascular Bundle/metabolism ; Seeds/*metabolism ; Sequence Homology, Amino Acid ; *Stem Cell Niche ; }, abstract = {Evolutionary studies addressing plant architecture have uncovered several significant dichotomies between lower and higher land plant radiations, which are based on differences in meristem histology and function. Here, we assess the establishment of different stem cell niches during land plant evolution based on genes of the stem cell-promoting WUSCHEL (WUS) clade of the WOX (WUSCHEL-related homeobox) gene family. WOX gene orthology was addressed by phylogenetic analyses of full-length WOX protein sequences and cellular expression pattern studies indicate process homology. Gene amplifications in the WUS clade were present in the last common ancestor (LCA) of extant gymnosperms and angiosperms. Whereas the evolution of complex multicellular shoot and root meristems relates to members in the WUS/WOX5 sub-branch, the evolution of marginal and plate meristems or the vascular cambium is associated with gene duplications that gave rise to WOX3 and WOX4, respectively. A fourth WUS clade member, WOX2, was apparently recruited for apical cell fate specification during early embryogenesis. The evolution and functional interplay of WOX3 and WOX4 possibly promoted a novel mode of leaf development, and evolutionary adaptations in their activities have contributed to the great diversity in shape and architecture of leaves in seed plants.}, } @article {pmid23702537, year = {2013}, author = {Himmel, HM}, title = {Drug-induced functional cardiotoxicity screening in stem cell-derived human and mouse cardiomyocytes: effects of reference compounds.}, journal = {Journal of pharmacological and toxicological methods}, volume = {68}, number = {1}, pages = {97-111}, doi = {10.1016/j.vascn.2013.05.005}, pmid = {23702537}, issn = {1873-488X}, mesh = {Animals ; Dimethyl Sulfoxide/chemistry ; Electric Impedance ; High-Throughput Screening Assays/methods ; Humans ; Induced Pluripotent Stem Cells/*cytology ; Mice ; Myocardial Contraction/*drug effects ; Myocytes, Cardiac/*drug effects/metabolism ; Reproducibility of Results ; Solvents/chemistry ; Species Specificity ; Time Factors ; Toxicity Tests/*methods ; }, abstract = {INTRODUCTION: Early prediction of drug-induced functional cardiotoxicity requires robust in-vitro systems suitable for medium/high throughput and easily accessible cardiomyocytes with defined reproducible properties. The xCELLigence Cardio system uses 96-well plates with interdigitated electrodes that detect the impedance changes of rhythmic contractions of stem cell-derived cardiomyocyte (SC-CM) layers. Here, we report on our initial screening experience in comparison to established (multi)cellular and in-vivo models.

METHODS: Impedance signals from human iPSC-CM (iCells™) and mouse eSC-CM (Cor.At™) were analyzed for contraction amplitude (CA) and duration, rise/fall time, beating rate (BR) and irregularity.

RESULTS: Following solution exchange, impedance signals re-approximated steady-state conditions after about 2 (Cor.At™) and 3h (iCells™); these time points were used to analyze drug effects. The solvent DMSO (≤1%) hardly influenced contraction parameters in Cor.At™, whereas in iCells™ DMSO (>0.1%) reduced CA and enhanced BR. The selective hERG K⁺ channel blockers E-4031 and dofetilide reduced CA and accelerated BR (≥30 nM) according to the analysis software. The latter, however, was due to burst-like contractions (300 nM) that could be detected only by visual inspection of recordings, and were more pronounced in Cor.At™ as in iCells™. In cardiac myocytes and tissue preparations, however, E4031 and dofetilide have been reported to increase cell shortening and contractile force and to reduce BR. Compounds (pentamidine, HMR1556, ATX2, TTX, and verapamil) with other mechanisms of action were also investigated; their effects differed partially between cell lines (e.g. TTX) and compared to established (multi)cellular models (e.g. HMR1556, ouabain).

CONCLUSION: Mouse and human stem cell-derived cardiomyocytes respond differently to drugs and these responses occasionally also differ from those originating from established in-vitro and in-vivo models. Hence, drug-induced cardiotoxic effects may be detected with this system, however, the predictive or even translational value of results is considered limited and not yet firmly established.}, } @article {pmid23700149, year = {2014}, author = {Henriksen, K and Karsdal, MA and Martin, TJ}, title = {Osteoclast-derived coupling factors in bone remodeling.}, journal = {Calcified tissue international}, volume = {94}, number = {1}, pages = {88-97}, doi = {10.1007/s00223-013-9741-7}, pmid = {23700149}, issn = {1432-0827}, mesh = {Animals ; Bone Remodeling/*genetics/physiology ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Osteoblasts/cytology/metabolism ; Osteoclasts/cytology/*metabolism ; Osteogenesis/physiology ; }, abstract = {In the bone remodeling process that takes place throughout the skeleton at bone multicellular units, intercellular communication processes are crucial. The osteoblast lineage has long been known to program osteoclast formation and hence resorption, but the preservation of bone mass and integrity requires tight control of remodeling. This needs local controls that ensure availability of mesenchymal precursors and the provision of local signals that promote differentiation through the osteoblast lineage. Some signals can come from growth factors released from resorbed bone matrix, and there is increasing evidence that the osteoclast lineage itself produces factors that can either enhance or inhibit osteoblast differentiation and hence bone formation. A number of such factors have been identified from predominantly in vitro experiments. The coupling of bone formation to resorption is increasingly recognized as a complex, dynamic process that results from the input of many local factors of cell and matrix origin that can either promote or inhibit bone formation.}, } @article {pmid23690618, year = {2013}, author = {Pires, ND and Yi, K and Breuninger, H and Catarino, B and Menand, B and Dolan, L}, title = {Recruitment and remodeling of an ancient gene regulatory network during land plant evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {23}, pages = {9571-9576}, pmid = {23690618}, issn = {1091-6490}, support = {BBS/E/J/0000A241/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Arabidopsis/*genetics ; Arabidopsis Proteins/*genetics ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Bryopsida/*genetics ; *Evolution, Molecular ; Gene Expression Regulation, Plant/genetics ; Gene Regulatory Networks/*genetics ; Molecular Sequence Data ; Multigene Family/*genetics ; Phylogeny ; Plant Roots/genetics/physiology ; Sequence Alignment ; Species Specificity ; }, abstract = {The evolution of multicellular organisms was made possible by the evolution of underlying gene regulatory networks. In animals, the core of gene regulatory networks consists of kernels, stable subnetworks of transcription factors that are highly conserved in distantly related species. However, in plants it is not clear when and how kernels evolved. We show here that RSL (ROOT HAIR DEFECTIVE SIX-LIKE) transcription factors form an ancient land plant kernel controlling caulonema differentiation in the moss Physcomitrella patens and root hair development in the flowering plant Arabidopsis thaliana. Phylogenetic analyses suggest that RSL proteins evolved in aquatic charophyte algae or in early land plants, and have been conserved throughout land plant radiation. Genetic and transcriptional analyses in loss of function A. thaliana and P. patens mutants suggest that the transcriptional interactions in the RSL kernel were remodeled and became more hierarchical during the evolution of vascular plants. We predict that other gene regulatory networks that control development in derived groups of plants may have originated in the earliest land plants or in their ancestors, the Charophycean algae.}, } @article {pmid23690137, year = {2013}, author = {Kutchko, KM and Siltberg-Liberles, J}, title = {Metazoan innovation: from aromatic amino acids to extracellular signaling.}, journal = {Amino acids}, volume = {45}, number = {2}, pages = {359-367}, pmid = {23690137}, issn = {1438-2199}, support = {P20 GM103432/GM/NIGMS NIH HHS/United States ; P20 RR016474/RR/NCRR NIH HHS/United States ; }, mesh = {Amino Acids, Aromatic/*chemistry/*metabolism ; Animals ; Eukaryota/enzymology/*metabolism ; Evolution, Molecular ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Phylogeny ; Sequence Alignment ; Signal Transduction ; Tyrosine/*metabolism ; }, abstract = {Tyrosine depletion in metazoan proteins was recently explained to be due to the appearance of tyrosine kinases in Metazoa. Here, we present a complementary explanation for the depletion of tyrosine, stating the importance of tyrosine in signaling not only as a phosphorylation target but also as a precursor for catecholamines and hormones. Molecules (dopamine, norepinephrine, and epinephrine, and to a lesser extent serotonin and melatonin) critical to metazoan multicellular signaling are also greatly dependent on a supply of tyrosine. These signaling molecules are synthesized in two highly linked pathways specific to metazoans. In addition, the shikimate pathway that non-metazoans use to synthesize the aromatic amino acids is not present in metazoans. These important pathway changes have occurred between Metazoa and other eukaryotes, causing significant changes to tyrosine metabolism and rendering tyrosine crucial for extracellular signaling. In addition, the evolutionary and functional linkage between these two pathways and the resulting implications for neuropathology are discussed.}, } @article {pmid23671590, year = {2013}, author = {Lenart, A and Dudkiewicz, M and Grynberg, M and Pawłowski, K}, title = {CLCAs - a family of metalloproteases of intriguing phylogenetic distribution and with cases of substituted catalytic sites.}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e62272}, pmid = {23671590}, issn = {1932-6203}, mesh = {Amino Acid Motifs/genetics ; Amino Acid Sequence ; Archaeal Proteins/genetics ; Bacterial Proteins/genetics ; Databases, Protein ; Genome, Human/*genetics ; Humans ; Metalloproteases/classification/*genetics ; Molecular Sequence Data ; Multigene Family/*genetics ; *Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {The zinc-dependent metalloproteases with His-Glu-x-x-His (HExxH) active site motif, zincins, are a broad group of proteins involved in many metabolic and regulatory functions, and found in all forms of life. Human genome contains more than 100 genes encoding proteins with known zincin-like domains. A survey of all proteins containing the HExxH motif shows that approximately 52% of HExxH occurrences fall within known protein structural domains (as defined in the Pfam database). Domain families with majority of members possessing a conserved HExxH motif include, not surprisingly, many known and putative metalloproteases. Furthermore, several HExxH-containing protein domains thus identified can be confidently predicted to be putative peptidases of zincin fold. Thus, we predict zincin-like fold for eight uncharacterised Pfam families. Besides the domains with the HExxH motif strictly conserved, and those with sporadic occurrences, intermediate families are identified that contain some members with a conserved HExxH motif, but also many homologues with substitutions at the conserved positions. Such substitutions can be evolutionarily conserved and non-random, yet functional roles of these inactive zincins are not known. The CLCAs are a novel zincin-like protease family with many cases of substituted active sites. We show that this allegedly metazoan family has a number of bacterial and archaeal members. An extremely patchy phylogenetic distribution of CLCAs in prokaryotes and their conserved protein domain composition strongly suggests an evolutionary scenario of horizontal gene transfer (HGT) from multicellular eukaryotes to bacteria, providing an example of eukaryote-derived xenologues in bacterial genomes. Additionally, in a protein family identified here as closely homologous to CLCA, the CLCA_X (CLCA-like) family, a number of proteins is found in phages and plasmids, supporting the HGT scenario.}, } @article {pmid23666537, year = {2013}, author = {Nunoura, T and Hirai, M and Miyazaki, M and Kazama, H and Makita, H and Hirayama, H and Furushima, Y and Yamamoto, H and Imachi, H and Takai, K}, title = {Isolation and characterization of a thermophilic, obligately anaerobic and heterotrophic marine Chloroflexi bacterium from a Chloroflexi-dominated microbial community associated with a Japanese shallow hydrothermal system, and proposal for Thermomarinilinea lacunofontalis gen. nov., sp. nov.}, journal = {Microbes and environments}, volume = {28}, number = {2}, pages = {228-235}, pmid = {23666537}, issn = {1347-4405}, mesh = {Anaerobiosis ; Bacterial Typing Techniques ; Chloroflexi/*classification/genetics/*isolation & purification/physiology ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Heterotrophic Processes ; Hydrogen-Ion Concentration ; Hydrothermal Vents/*microbiology ; Japan ; Molecular Sequence Data ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sodium Chloride/metabolism ; Temperature ; }, abstract = {A novel marine thermophilic and heterotrophic Anaerolineae bacterium in the phylum Chloroflexi, strain SW7(T), was isolated from an in situ colonization system deployed in the main hydrothermal vent of the Taketomi submarine hot spring field located on the southern part of Yaeyama Archipelago, Japan. The microbial community associated with the hydrothermal vent was predominated by thermophilic heterotrophs such as Thermococcaceae and Anaerolineae, and the next dominant population was thermophilic sulfur oxidizers. Both aerobic and anaerobic hydrogenotrophs including methanogens were detected as minor populations. During the culture-dependent viable count analysis in this study, an Anaerolineae strain SW7(T) was isolated from an enrichment culture at a high dilution rate. Strain SW7(T) was an obligately anaerobic heterotroph that grew with fermentation and had non-motile thin rods 3.5-16.5 μm in length and 0.2 μm in width constituting multicellular filaments. Growth was observed between 37-65°C (optimum 60°C), pH 5.5-7.3 (optimum pH 6.0), and 0.5-3.5% (w/v) NaCl concentration (optimum 1.0%). Based on the physiological and phylogenetic features of a new isolate, we propose a new species representing a novel genus Thermomarinilinea: the type strain of Thermomarinilinea lacunofontalis sp. nov., is SW7(T) (=JCM15506(T)=KCTC5908(T)).}, } @article {pmid23665876, year = {2013}, author = {Hall, DW and Fox, S and Kuzdzal-Fick, JJ and Strassmann, JE and Queller, DC}, title = {The rate and effects of spontaneous mutation on fitness traits in the social amoeba, Dictyostelium discoideum.}, journal = {G3 (Bethesda, Md.)}, volume = {3}, number = {7}, pages = {1115-1127}, pmid = {23665876}, issn = {2160-1836}, mesh = {Dictyostelium/*genetics ; Evolution, Molecular ; *Genetic Fitness ; Mutation/*genetics ; Mutation Rate ; Saccharomyces cerevisiae/genetics ; }, abstract = {We performed a mutation accumulation (MA) experiment in the social amoeba Dictyostelium discoideum to estimate the rate and distribution of effects of spontaneous mutations affecting eight putative fitness traits. We found that the per-generation mutation rate for most fitness components is 0.0019 mutations per haploid genome per generation or larger. This rate is an order of magnitude higher than estimates for fitness components in the unicellular eukaryote Saccharomyces cerevisiae, even though the base-pair substitution rate is two orders of magnitude lower. The high rate of fitness-altering mutations observed in this species may be partially explained by a large mutational target relative to S. cerevisiae. Fitness-altering mutations also may occur primarily at simple sequence repeats, which are common throughout the genome, including in coding regions, and may represent a target that is particularly likely to give fitness effects upon mutation. The majority of mutations had deleterious effects on fitness, but there was evidence for a substantial fraction, up to 40%, being beneficial for some of the putative fitness traits. Competitive ability within the multicellular slug appears to be under weak directional selection, perhaps reflecting the fact that slugs are sometimes, but not often, comprised of multiple clones in nature. Evidence for pleiotropy among fitness components across MA lines was absent, suggesting that mutations tend to act on single fitness components.}, } @article {pmid23662904, year = {2013}, author = {Harrison, F}, title = {Dynamic social behaviour in a bacterium: pseudomonas aeruginosa partially compensates for siderophore loss to cheats.}, journal = {Journal of evolutionary biology}, volume = {26}, number = {6}, pages = {1370-1378}, doi = {10.1111/jeb.12126}, pmid = {23662904}, issn = {1420-9101}, mesh = {Biological Evolution ; Pseudomonas aeruginosa/*physiology ; Siderophores/*metabolism ; }, abstract = {Cooperation underlies diverse phenomena including the origins of multicellular life, human behaviour in economic markets and the mechanisms by which pathogenic bacteria cause disease. Experiments with microorganisms have advanced our understanding of how, when and why cooperation evolves, but the extent to which microbial cooperation can recapitulate aspects of animal behaviour is debated. For instance, understanding the evolution of behavioural response rules (how should one individual respond to another's decision to cooperate or defect?) is a key part of social evolution theory, but the possible existence of such rules in social microbes has not been explored. In one specific context (biparental care in animals), cooperation is maintained if individuals respond to a partner's defection by increasing their own investment into cooperation, but not so much that this fully compensates for the defector's lack of investment. This is termed 'partial compensation'. Here, I show that partial compensation for the presence of noncooperating 'cheats' is also observed in a microbial social behaviour: the cooperative production of iron-scavenging siderophores by the bacterium Pseudomonas aeruginosa. A period of evolution in the presence of cheats maintains this response, whereas evolution in the absence of cheats leads to a loss of compensatory behaviour. These results demonstrate (i) the remarkable flexibility of bacterial social behaviour, (ii) the potential generality of partial compensation as a social response rule and (iii) the need for mathematical models to explore the evolution of response rules in multi-player social interactions.}, } @article {pmid23662577, year = {2013}, author = {Teriukova, NP and Blinova, GI and Ivanov, VA}, title = {[Zajdela hepatoma cells cultured in vitro].}, journal = {Tsitologiia}, volume = {55}, number = {1}, pages = {36-44}, pmid = {23662577}, issn = {0041-3771}, mesh = {Animals ; Antibodies, Neoplasm/immunology ; *Antigens, Neoplasm/biosynthesis/immunology ; *Carcinoma, Hepatocellular/immunology/metabolism/pathology ; Cell Line, Tumor ; *Liver Neoplasms/immunology/metabolism/pathology ; Male ; Rabbits ; Rats ; *Spheroids, Cellular/immunology/metabolism/pathology ; }, abstract = {Two continuous cell lines, monolayer (ZH-ad) and suspension (ZH-fl), which doffer in the level of cell differentiation and tumorigenicity, were obtained from explants of ascitic Zajdela hepatoma. Using tumor-specific rabbit immune serum tumor-associated antigens were detected in the fraction of plasma membrane of ZH-fl cells, synthesis of that was reduced or suppressed in ZH-ad cells. Intraperitoneal injection of ZH-fl cells as few as 0.5 - 10(6) cells/rat was enough for development of ascites tumor, while minimal dose for ZH-ad cells increase to 20 - 10(6) cells. Three types of generated clones were revealed by means of clonogenic analysis of ZH-fl cells: nonadhesive sphere colonies and two types of monolayer clones ranging in proliferative potential, shape of colonies and cell composition. When the spherical colonies had reached a critical size they disintegrated with dissociation of single cells or islets of various sizes, part of which attached to the plate to form a monolayer. Three clonal cell lines were obtained: IC - as a result of expansion of sphere clone cells, 4G and 10E - from monolayer clones. Our results demonstrate a clonogenic origin of multicellular islets of ascetic hepatoma Zajdela.}, } @article {pmid23645554, year = {2013}, author = {Bhattacharya, D and Pelletreau, KN and Price, DC and Sarver, KE and Rumpho, ME}, title = {Genome analysis of Elysia chlorotica Egg DNA provides no evidence for horizontal gene transfer into the germ line of this Kleptoplastic Mollusc.}, journal = {Molecular biology and evolution}, volume = {30}, number = {8}, pages = {1843-1852}, pmid = {23645554}, issn = {1537-1719}, mesh = {Animals ; Computational Biology/methods ; *DNA ; Databases, Nucleic Acid ; Gastropoda/*genetics/metabolism ; *Gene Transfer, Horizontal ; *Genomics ; Germ Cells/*metabolism ; Transcription, Genetic ; }, abstract = {The sea slug Elysia chlorotica offers a unique opportunity to study the evolution of a novel function (photosynthesis) in a complex multicellular host. Elysia chlorotica harvests plastids (absent of nuclei) from its heterokont algal prey, Vaucheria litorea. The "stolen" plastids are maintained for several months in cells of the digestive tract and are essential for animal development. The basis of long-term maintenance of photosynthesis in this sea slug was thought to be explained by extensive horizontal gene transfer (HGT) from the nucleus of the alga to the animal nucleus, followed by expression of algal genes in the gut to provide essential plastid-destined proteins. Early studies of target genes and proteins supported the HGT hypothesis, but more recent genome-wide data provide conflicting results. Here, we generated significant genome data from the E. chlorotica germ line (egg DNA) and from V. litorea to test the HGT hypothesis. Our comprehensive analyses fail to provide evidence for alga-derived HGT into the germ line of the sea slug. Polymerase chain reaction analyses of genomic DNA and cDNA from different individual E. chlorotica suggest, however, that algal nuclear genes (or gene fragments) are present in the adult slug. We suggest that these nucleic acids may derive from and/or reside in extrachromosomal DNAs that are made available to the animal through contact with the alga. These data resolve a long-standing issue and suggest that HGT is not the primary reason underlying long-term maintenance of photosynthesis in E. chlorotica. Therefore, sea slug photosynthesis is sustained in as yet unexplained ways that do not appear to endanger the animal germ line through the introduction of dozens of foreign genes.}, } @article {pmid23634722, year = {2013}, author = {Aguilera, F and McDougall, C and Degnan, BM}, title = {Origin, evolution and classification of type-3 copper proteins: lineage-specific gene expansions and losses across the Metazoa.}, journal = {BMC evolutionary biology}, volume = {13}, number = {}, pages = {96}, pmid = {23634722}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; Catechol Oxidase/chemistry/*genetics/metabolism ; Copper/metabolism ; Eukaryota/chemistry/classification/*genetics ; *Evolution, Molecular ; *Gene Deletion ; *Gene Duplication ; Hemocyanins/chemistry/*genetics/metabolism ; Humans ; Molecular Sequence Data ; Monophenol Monooxygenase/chemistry/*genetics/metabolism ; Phylogeny ; Protein Structure, Tertiary ; Sequence Alignment ; Species Specificity ; }, abstract = {BACKGROUND: Tyrosinases, tyrosinase-related proteins, catechol oxidases and hemocyanins comprise the type-3 copper protein family and are involved in a variety of biological processes, including pigment formation, innate immunity and oxygen transport. Although this family is present in the three domains of life, its origin and early evolution are not well understood. Previous analyses of type-3 copper proteins largely have focussed on specific animal and plant phyla.

RESULTS: Here, we combine genomic, phylogenetic and structural analyses to show that the original type-3 copper protein possessed a signal peptide and may have been secreted (we designate proteins of this type the α subclass). This ancestral type-3 copper protein gene underwent two duplication events, the first prior to the divergence of the unikont eukaryotic lineages and the second before the diversification of animals. The former duplication gave rise to a cytosolic form (β) and the latter to a membrane-bound form (γ). Structural comparisons reveal that the active site of α and γ forms are covered by aliphatic amino acids, and the β form has a highly conserved aromatic residue in this position. The subsequent evolution of this gene family in modern lineages of multicellular eukaryotes is typified by the loss of one or more of these three subclasses and the lineage-specific expansion of one or both of the remaining subclasses.

CONCLUSIONS: The diversity of type-3 copper proteins in animals and other eukaryotes is consistent with two ancient gene duplication events leading to α, β and γ subclasses, followed by the differential loss and expansion of one or more of these subclasses in specific kingdoms and phyla. This has led to many lineage-specific type-3 copper protein repertoires and in some cases the independent evolution of functionally-classified tyrosinases and hemocyanins. For example, the oxygen-carrying hemocyanins in arthropods evolved from a β-subclass tyrosinase, whilst hemocyanins in molluscs and urochordates evolved independently from an α-subclass tyrosinase. Minor conformational changes at the active site of α, β and γ forms can produce type-3 copper proteins with capacities to either carry oxygen (hemocyanins), oxidize diphenols (catechol oxidase) or o-hydroxylate monophenols (tyrosinases) and appear to underlie some functional convergences.}, } @article {pmid23632774, year = {2014}, author = {Buenzli, PR and Pivonka, P and Smith, DW}, title = {Bone refilling in cortical basic multicellular units: insights into tetracycline double labelling from a computational model.}, journal = {Biomechanics and modeling in mechanobiology}, volume = {13}, number = {1}, pages = {185-203}, doi = {10.1007/s10237-013-0495-y}, pmid = {23632774}, issn = {1617-7940}, mesh = {*Bone Remodeling ; Calibration ; *Computer Simulation ; Tetracycline/*chemistry ; }, abstract = {Bone remodelling is carried out by 'bone multicellular units' ([Formula: see text]s) in which active osteoclasts and active osteoblasts are spatially and temporally coupled. The refilling of new bone by osteoblasts towards the back of the [Formula: see text] occurs at a rate that depends both on the number of osteoblasts and on their secretory activity. In cortical bone, a linear phenomenological relationship between matrix apposition rate and [Formula: see text] cavity radius is found experimentally. How this relationship emerges from the combination of complex, nonlinear regulations of osteoblast number and secretory activity is unknown. Here, we extend our previous mathematical model of cell development within a single cortical [Formula: see text] to investigate how osteoblast number and osteoblast secretory activity vary along the [Formula: see text]'s closing cone. The mathematical model is based on biochemical coupling between osteoclasts and osteoblasts of various maturity and includes the differentiation of osteoblasts into osteocytes and bone lining cells, as well as the influence of [Formula: see text] cavity shrinkage on osteoblast development and activity. Matrix apposition rates predicted by the model are compared with data from tetracycline double labelling experiments. We find that the linear phenomenological relationship observed in these experiments between matrix apposition rate and [Formula: see text] cavity radius holds for most of the refilling phase simulated by our model, but not near the start and end of refilling. This suggests that at a particular bone site undergoing remodelling, bone formation starts and ends rapidly, supporting the hypothesis that osteoblasts behave synchronously. Our model also suggests that part of the observed cross-sectional variability in tetracycline data may be due to different bone sites being refilled by [Formula: see text]s at different stages of their lifetime. The different stages of a [Formula: see text]'s lifetime (such as initiation stage, progression stage, and termination stage) depend on whether the cell populations within the [Formula: see text] are still developing or have reached a quasi-steady state whilst travelling through bone. We find that due to their longer lifespan, active osteoblasts reach a quasi-steady distribution more slowly than active osteoclasts. We suggest that this fact may locally enlarge the Haversian canal diameter (due to a local lack of osteoblasts compared to osteoclasts) near the [Formula: see text]'s point of origin.}, } @article {pmid23630532, year = {2013}, author = {Wondafrash, M and Van Dam, NM and Tytgat, TO}, title = {Plant systemic induced responses mediate interactions between root parasitic nematodes and aboveground herbivorous insects.}, journal = {Frontiers in plant science}, volume = {4}, number = {}, pages = {87}, pmid = {23630532}, issn = {1664-462X}, abstract = {Insects and nematodes are the most diverse and abundant groups of multicellular animals feeding on plants on either side of the soil-air interface. Several herbivore-induced responses are systemic, and hence can influence the preference and performance of organisms in other plant organs. Recent studies show that plants mediate interactions between belowground plant parasitic nematodes (PPNs) and aboveground herbivorous insects. Based on the knowledge of plant responses to pathogens, we review the emerging insights on plant systemic responses against root-feeding nematodes and shoot-feeding insects. We discuss the potential mechanisms of plant-mediated indirect interactions between both groups of organisms and point to gaps in our knowledge. Root-feeding nematodes can positively or negatively affect shoot herbivorous insects, and vice versa. The outcomes of the interactions between these spatially separated herbivore communities appear to be influenced by the feeding strategy of the nematodes and the insects, as well as by host plant susceptibility to both herbivores. The potential mechanisms for these interactions include systemic induced plant defense, interference with the translocation and dynamics of locally induced secondary metabolites, and reallocation of plant nutritional reserves. During evolution, PPNs as well as herbivorous insects have acquired effectors that modify plant defense responses and resource allocation patterns to their advantage. However, it is also known that plants under herbivore attack change the allocation of their resources, e.g., for compensatory growth responses, which may affect the performance of other organisms feeding on the plant. Studying the chemical and molecular basis of these interactions will reveal the molecular mechanisms that are involved. Moreover, it will lead to a better understanding of the ecological relevance of aboveground-belowground interactions, as well as support the development of sustainable pest management technologies.}, } @article {pmid23615877, year = {2013}, author = {Tarabichi, M and Antoniou, A and Saiselet, M and Pita, JM and Andry, G and Dumont, JE and Detours, V and Maenhaut, C}, title = {Systems biology of cancer: entropy, disorder, and selection-driven evolution to independence, invasion and "swarm intelligence".}, journal = {Cancer metastasis reviews}, volume = {32}, number = {3-4}, pages = {403-421}, pmid = {23615877}, issn = {1573-7233}, mesh = {Animals ; Cell Transformation, Neoplastic ; Humans ; Neoplasm Metastasis ; Neoplasms/*etiology/*pathology ; *Systems Biology ; }, abstract = {Our knowledge of the biology of solid cancer has greatly progressed during the last few years, and many excellent reviews dealing with the various aspects of this biology have appeared. In the present review, we attempt to bring together these subjects in a general systems biology narrative. It starts from the roles of what we term entropy of signaling and noise in the initial oncogenic events, to the first major transition of tumorigenesis: the independence of the tumor cell and the switch in its physiology, i.e., from subservience to the organism to its own independent Darwinian evolution. The development after independence involves a constant dynamic reprogramming of the cells and the emergence of a sort of collective intelligence leading to invasion and metastasis and seldom to the ultimate acquisition of immortality through inter-individual infection. At each step, the probability of success is minimal to infinitesimal, but the number of cells possibly involved and the time scale account for the relatively high occurrence of tumorigenesis and metastasis in multicellular organisms.}, } @article {pmid23613593, year = {2013}, author = {Pechkovsky, A and Lahav, M and Bitman, E and Salzberg, A and Kleinberger, T}, title = {E4orf4 induces PP2A- and Src-dependent cell death in Drosophila melanogaster and at the same time inhibits classic apoptosis pathways.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {19}, pages = {E1724-33}, pmid = {23613593}, issn = {1091-6490}, mesh = {Animals ; *Apoptosis ; Caspases/metabolism ; Conserved Sequence ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/*metabolism ; Female ; *Gene Expression Regulation, Enzymologic ; Male ; Models, Genetic ; Phenotype ; Phosphoprotein Phosphatases/*metabolism ; Photoreceptor Cells, Invertebrate/physiology ; Transgenes ; Viral Proteins/*genetics/metabolism ; Wings, Animal/physiology ; src-Family Kinases/*metabolism ; }, abstract = {The adenovirus E4orf4 protein regulates the progression of viral infection, and when expressed alone in mammalian tissue culture cells it induces protein phosphatase 2A (PP2A)-B55- and Src-dependent cell death, which is more efficient in oncogene-transformed cells than in normal cells. This form of cell death is caspase-independent, although it interacts with classic caspase-dependent apoptosis. PP2A-B55-dependent E4orf4-induced toxicity is highly conserved in evolution from yeast to mammalian cells. In this work we investigated E4orf4-induced cell death in a whole multicellular organism, Drosophila melanogaster. We show that E4orf4 induced low levels of cell killing, caused by both caspase-dependent and -independent mechanisms. Drosophila PP2A-B55 (twins/abnormal anaphase resolution) and Src64B contributed additively to this form of cell death. Our results provide insight into E4orf4-induced cell death, demonstrating that in parallel to activating caspase-dependent apoptosis, E4orf4 also inhibited this form of cell death induced by the proapoptotic genes reaper, head involution defective, and grim. The combination of both induction and inhibition of caspase-dependent cell death resulted in low levels of tissue damage that may explain the inefficient cell killing induced by E4orf4 in normal cells in tissue culture. Furthermore, E4orf4 inhibited JNK-dependent cell killing as well. However, JNK inhibition did not impede E4orf4-induced toxicity and even enhanced it, indicating that E4orf4-induced cell killing is a distinctive form of cell death that differs from both JNK- and Rpr/Hid/Grim-induced forms of cell death.}, } @article {pmid23611907, year = {2013}, author = {Gyawali, R and Lin, X}, title = {Prezygotic and postzygotic control of uniparental mitochondrial DNA inheritance in Cryptococcus neoformans.}, journal = {mBio}, volume = {4}, number = {2}, pages = {e00112-13}, pmid = {23611907}, issn = {2150-7511}, support = {R01 AI097599/AI/NIAID NIH HHS/United States ; }, mesh = {Cryptococcus neoformans/*genetics ; DNA, Mitochondrial/*genetics ; Genes, Mating Type, Fungal ; *Genes, Mitochondrial ; Time Factors ; }, abstract = {UNLABELLED: Uniparental inheritance of mitochondrial DNA is pervasive in nonisogamic higher eukaryotes during sexual reproduction, and postzygotic and/or prezygotic factors are shown to be important in ensuring such an inheritance pattern. Although the fungus Cryptococcus neoformans undergoes sexual production with isogamic partners of opposite mating types a and α, most progeny derived from such mating events inherit the mitochondrial DNA (mtDNA) from the a parent. The homeodomain protein complex Sxi1α/Sxi2a, formed in the zygote after a-α cell fusion, was previously shown to play a role in this uniparental mtDNA inheritance. Here, we defined the timing of the establishment of the mtDNA inheritance pattern during the mating process and demonstrated a critical role in determining the mtDNA inheritance pattern by a prezygotic factor, Mat2. Mat2 is the key transcription factor that governs the pheromone sensing and response pathway, and it is critical for the early mating events that lead to cell fusion and zygote formation. We show that Mat2 governs mtDNA inheritance independently of the postzygotic factors Sxi1α/Sxi2a, and the cooperation between these prezygotic and postzygotic factors helps to achieve stricter uniparental mitochondrial inheritance in this eukaryotic microbe.

IMPORTANCE: Mitochondrial DNA is inherited uniparentally from the maternal parent in the majority of eukaryotes. Studies done on higher eukaryotes such as mammals have shown that the transmission of parental mitochondrial DNA is controlled at both the prefertilization and postfertilization stages to achieve strict uniparental inheritance. However, the molecular mechanisms underlying such uniparental mitochondrial inheritance have been investigated in detail mostly in anisogamic multicellular eukaryotes. Here, we show that in a simple isogamic microbe, Cryptococcus neoformans, the mitochondrial inheritance is controlled at the prezygotic level as well as the postzygotic level by regulators that are critical for sexual development. Furthermore, the cooperation between these two levels of control ensures stricter uniparental mitochondrial inheritance, echoing what has been observed in higher eukaryotes. Thus, the investigation of uniparental mitochondrial inheritance in this eukaryotic microbe could help advance our understanding of the convergent evolution of this widespread phenomenon in the eukaryotic domain.}, } @article {pmid23597031, year = {2013}, author = {Taylor-Brown, E and Hurd, H}, title = {The first suicides: a legacy inherited by parasitic protozoans from prokaryote ancestors.}, journal = {Parasites & vectors}, volume = {6}, number = {}, pages = {108}, pmid = {23597031}, issn = {1756-3305}, mesh = {*Apoptosis ; Bacteria/genetics ; Biological Evolution ; Leishmania/genetics/*physiology ; Mitochondria/metabolism ; Phenotype ; Plasmodium/genetics/*physiology ; Trypanosoma/genetics/*physiology ; }, abstract = {It is more than 25 years since the first report that a protozoan parasite could die by a process resulting in a morphological phenotype akin to apoptosis. Since then these phenotypes have been observed in many unicellular parasites, including trypanosomatids and apicomplexans, and experimental evidence concerning the molecular pathways that are involved is growing. These observations support the view that this form of programmed cell death is an ancient one that predates the evolution of multicellularity. Here we review various hypotheses that attempt to explain the origin of apoptosis, and look for support for these hypotheses amongst the parasitic protists as, with the exception of yeast, most of the work on death mechanisms in unicellular organisms has focussed on them. We examine the role that addiction modules may have played in the original eukaryote cell and the part played by mitochondria in the execution of present day cells, looking for examples from Leishmania spp. Trypanosoma spp. and Plasmodium spp. In addition, the expanding knowledge of proteases, nucleases and other molecules acting in protist execution pathways has enabled comparisons to be made with extant Archaea and bacteria and with biochemical pathways that evolved in metazoans. These comparisons lend support to the original sin hypothesis but also suggest that present-day death pathways may have had multifaceted beginnings.}, } @article {pmid23596570, year = {2013}, author = {Szabó, A and Merks, RM}, title = {Cellular potts modeling of tumor growth, tumor invasion, and tumor evolution.}, journal = {Frontiers in oncology}, volume = {3}, number = {}, pages = {87}, pmid = {23596570}, issn = {2234-943X}, abstract = {Despite a growing wealth of available molecular data, the growth of tumors, invasion of tumors into healthy tissue, and response of tumors to therapies are still poorly understood. Although genetic mutations are in general the first step in the development of a cancer, for the mutated cell to persist in a tissue, it must compete against the other, healthy or diseased cells, for example by becoming more motile, adhesive, or multiplying faster. Thus, the cellular phenotype determines the success of a cancer cell in competition with its neighbors, irrespective of the genetic mutations or physiological alterations that gave rise to the altered phenotype. What phenotypes can make a cell "successful" in an environment of healthy and cancerous cells, and how? A widely used tool for getting more insight into that question is cell-based modeling. Cell-based models constitute a class of computational, agent-based models that mimic biophysical and molecular interactions between cells. One of the most widely used cell-based modeling formalisms is the cellular Potts model (CPM), a lattice-based, multi particle cell-based modeling approach. The CPM has become a popular and accessible method for modeling mechanisms of multicellular processes including cell sorting, gastrulation, or angiogenesis. The CPM accounts for biophysical cellular properties, including cell proliferation, cell motility, and cell adhesion, which play a key role in cancer. Multiscale models are constructed by extending the agents with intracellular processes including metabolism, growth, and signaling. Here we review the use of the CPM for modeling tumor growth, tumor invasion, and tumor progression. We argue that the accessibility and flexibility of the CPM, and its accurate, yet coarse-grained and computationally efficient representation of cell and tissue biophysics, make the CPM the method of choice for modeling cellular processes in tumor development.}, } @article {pmid23596506, year = {2013}, author = {Solé, RV and Valverde, S}, title = {Before the endless forms: embodied model of transition from single cells to aggregates to ecosystem engineering.}, journal = {PloS one}, volume = {8}, number = {4}, pages = {e59664}, pmid = {23596506}, issn = {1932-6203}, mesh = {Algorithms ; *Biological Evolution ; *Cell Communication ; *Cell Physiological Phenomena ; Computer Simulation ; Environment ; *Models, Theoretical ; Morphogenesis/physiology ; }, abstract = {The emergence of complex multicellular systems and their associated developmental programs is one of the major problems of evolutionary biology. The advantages of cooperation over individuality seem well known but it is not clear yet how such increase of complexity emerged from unicellular life forms. Current multicellular systems display a complex cell-cell communication machinery, often tied to large-scale controls of body size or tissue homeostasis. Some unicellular life forms are simpler and involve groups of cells cooperating in a tissue-like fashion, as it occurs with biofilms. However, before true gene regulatory interactions were widespread and allowed for controlled changes in cell phenotypes, simple cellular colonies displaying adhesion and interacting with their environments were in place. In this context, models often ignore the physical embedding of evolving cells, thus leaving aside a key component. The potential for evolving pre-developmental patterns is a relevant issue: how far a colony of evolving cells can go? Here we study these pre-conditions for morphogenesis by using CHIMERA, a physically embodied computational model of evolving virtual organisms in a pre-Mendelian world. Starting from a population of identical, independent cells moving in a fluid, the system undergoes a series of changes, from spatial segregation, increased adhesion and the development of generalism. Eventually, a major transition occurs where a change in the flow of nutrients is triggered by a sub-population. This ecosystem engineering phenomenon leads to a subsequent separation of the ecological network into two well defined compartments. The relevance of these results for evodevo and its potential ecological triggers is discussed.}, } @article {pmid23586987, year = {2013}, author = {Omura, T}, title = {Contribution of cytochrome P450 to the diversification of eukaryotic organisms.}, journal = {Biotechnology and applied biochemistry}, volume = {60}, number = {1}, pages = {4-8}, doi = {10.1002/bab.1099}, pmid = {23586987}, issn = {1470-8744}, mesh = {Animals ; Biocatalysis ; *Biological Evolution ; Cytochrome P-450 Enzyme System/genetics/*metabolism ; Eukaryota/*enzymology/metabolism ; }, abstract = {Emergence of eukaryotic cells in the ancient world of prokaryotic life was dependent on P450 as the synthesis of sterols, an essential constituent of the plasma membrane, required a P450-catalyzed reaction. As the ancestral monocellular eukaryotic organisms evolved into multicellular eukaryotes, and then diversified to plants, fungi, and animals with different body organizations and metabolic activities, many novel compounds were created in order to meet the requirements for increasing complex metabolic activities of a wide variety of eukaryotic organisms. Many new P450s, created by gene duplication and mutation, contributed to the synthesis of those novel compounds in animals, plants, and fungi, and supported the diversification of the eukaryotes. Many secondary metabolites of plants, which protect the plants from the predation by herbivorous animals, were also synthesized by P450-catalyzed reactions. The herbivorous animals detoxified the noxious foreign compounds in the plants by P450. This "chemical warfare" between animals and plants is particularly evident in plants-insects interaction, and contributed to the coevolution and diversification of both plants and insects. The interaction between flowering plants and insect pollinators, which contributed to their coevolution, also depends on various plant compounds synthesized by P450-catalyzed reactions. P450 has made highly important contributions to the evolution and diversification of eukaryotic organisms.}, } @article {pmid23577236, year = {2013}, author = {Gresham, D}, title = {A sticky solution.}, journal = {eLife}, volume = {2}, number = {}, pages = {e00655}, pmid = {23577236}, issn = {2050-084X}, support = {R01 GM107466/GM/NIGMS NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; Monosaccharide Transport Proteins/*metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; Sucrose/*metabolism ; beta-Fructofuranosidase/*metabolism ; }, abstract = {Selection favours single-celled mutants that stick together when a sugar needed for growth is in short supply, suggesting that multicellular life may have evolved as a by-product of selection for more efficient usage of resources.}, } @article {pmid23577233, year = {2013}, author = {Koschwanez, JH and Foster, KR and Murray, AW}, title = {Improved use of a public good selects for the evolution of undifferentiated multicellularity.}, journal = {eLife}, volume = {2}, number = {}, pages = {e00367}, pmid = {23577233}, issn = {2050-084X}, support = {P50 GM068763/GM/NIGMS NIH HHS/United States ; GM06873/GM/NIGMS NIH HHS/United States ; K25GM085806/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; Biological Transport ; Cell Division ; *Evolution, Molecular ; Gene Expression Regulation, Fungal ; Genotype ; Hydrolysis ; Monosaccharide Transport Proteins/genetics/*metabolism ; Mutation ; Phenotype ; Saccharomyces cerevisiae/genetics/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Sucrose/*metabolism ; beta-Fructofuranosidase/genetics/*metabolism ; }, abstract = {We do not know how or why multicellularity evolved. We used the budding yeast, Saccharomyces cerevisiae, to ask whether nutrients that must be digested extracellularly select for the evolution of undifferentiated multicellularity. Because yeast use invertase to hydrolyze sucrose extracellularly and import the resulting monosaccharides, single cells cannot grow at low cell and sucrose concentrations. Three engineered strategies overcame this problem: forming multicellular clumps, importing sucrose before hydrolysis, and increasing invertase expression. We evolved populations in low sucrose to ask which strategy they would adopt. Of 12 successful clones, 11 formed multicellular clumps through incomplete cell separation, 10 increased invertase expression, none imported sucrose, and 11 increased hexose transporter expression, a strategy we had not engineered. Identifying causal mutations revealed genes and pathways, which frequently contributed to the evolved phenotype. Our study shows that combining rational design with experimental evolution can help evaluate hypotheses about evolutionary strategies. DOI:http://dx.doi.org/10.7554/eLife.00367.001.}, } @article {pmid23569284, year = {2013}, author = {Nguyen, DH and Stapleton, SC and Yang, MT and Cha, SS and Choi, CK and Galie, PA and Chen, CS}, title = {Biomimetic model to reconstitute angiogenic sprouting morphogenesis in vitro.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {17}, pages = {6712-6717}, pmid = {23569284}, issn = {1091-6490}, support = {UH2 EB017103/EB/NIBIB NIH HHS/United States ; T32 HL007954/HL/NHLBI NIH HHS/United States ; R01 GM104287/GM/NIGMS NIH HHS/United States ; HL007954/HL/NHLBI NIH HHS/United States ; R01 EB000262/EB/NIBIB NIH HHS/United States ; EB00262/EB/NIBIB NIH HHS/United States ; CA101871/CA/NCI NIH HHS/United States ; EB08396/EB/NIBIB NIH HHS/United States ; R01 EB008396/EB/NIBIB NIH HHS/United States ; R25 CA101871/CA/NCI NIH HHS/United States ; UH3 EB017103/EB/NIBIB NIH HHS/United States ; R01 DE016525/DE/NIDCR NIH HHS/United States ; }, mesh = {Biomimetics/*methods ; Cell Polarity/physiology ; Dimethylpolysiloxanes ; Fingolimod Hydrochloride ; Fluorescent Antibody Technique ; Human Umbilical Vein Endothelial Cells ; Humans ; Indoles/pharmacology ; Lysophospholipids/metabolism ; Microfluidics/*methods ; *Models, Biological ; Morphogenesis/drug effects/*physiology ; Neovascularization, Physiologic/drug effects/*physiology ; Propylene Glycols/pharmacology ; Pseudopodia/physiology ; Pyrroles/pharmacology ; Sphingosine/analogs & derivatives/metabolism/pharmacology ; Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors ; }, abstract = {Angiogenesis is a complex morphogenetic process whereby endothelial cells from existing vessels invade as multicellular sprouts to form new vessels. Here, we have engineered a unique organotypic model of angiogenic sprouting and neovessel formation that originates from preformed artificial vessels fully encapsulated within a 3D extracellular matrix. Using this model, we screened the effects of angiogenic factors and identified two distinct cocktails that promoted robust multicellular endothelial sprouting. The angiogenic sprouts in our system exhibited hallmark structural features of in vivo angiogenesis, including directed invasion of leading cells that developed filopodia-like protrusions characteristic of tip cells, following stalk cells exhibiting apical-basal polarity, and lumens and branches connecting back to the parent vessels. Ultimately, sprouts bridged between preformed channels and formed perfusable neovessels. Using this model, we investigated the effects of angiogenic inhibitors on sprouting morphogenesis. Interestingly, the ability of VEGF receptor 2 inhibition to antagonize filopodia formation in tip cells was context-dependent, suggesting a mechanism by which vessels might be able to toggle between VEGF-dependent and VEGF-independent modes of angiogenesis. Like VEGF, sphingosine-1-phosphate also seemed to exert its proangiogenic effects by stimulating directional filopodial extension, whereas matrix metalloproteinase inhibitors prevented sprout extension but had no impact on filopodial formation. Together, these results demonstrate an in vitro 3D biomimetic model that reconstitutes the morphogenetic steps of angiogenic sprouting and highlight the potential utility of the model to elucidate the molecular mechanisms that coordinate the complex series of events involved in neovascularization.}, } @article {pmid23563970, year = {2013}, author = {Grau-Bové, X and Sebé-Pedrós, A and Ruiz-Trillo, I}, title = {A genomic survey of HECT ubiquitin ligases in eukaryotes reveals independent expansions of the HECT system in several lineages.}, journal = {Genome biology and evolution}, volume = {5}, number = {5}, pages = {833-847}, pmid = {23563970}, issn = {1759-6653}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Animals ; Eukaryota/classification/*genetics ; *Evolution, Molecular ; Genome ; *Phylogeny ; Protein Structure, Tertiary ; Ubiquitin-Protein Ligases/classification/*genetics ; Ubiquitination/genetics ; }, abstract = {The posttranslational modification of proteins by the ubiquitination pathway is an important regulatory mechanism in eukaryotes. To date, however, studies on the evolutionary history of the proteins involved in this pathway have been restricted to E1 and E2 enzymes, whereas E3 studies have been focused mainly in metazoans and plants. To have a wider perspective, here we perform a genomic survey of the HECT family of E3 ubiquitin-protein ligases, an important part of this posttranslational pathway, in genomes from representatives of all major eukaryotic lineages. We classify eukaryotic HECTs and reconstruct, by phylogenetic analysis, the putative repertoire of these proteins in the last eukaryotic common ancestor (LECA). Furthermore, we analyze the diversity and complexity of protein domain architectures of HECTs along the different extant eukaryotic lineages. Our data show that LECA had six different HECTs and that protein expansion and N-terminal domain diversification shaped HECT evolution. Our data reveal that the genomes of animals and unicellular holozoans considerably increased the molecular and functional diversity of their HECT system compared with other eukaryotes. Other eukaryotes, such as the Apusozoa Thecanomas trahens or the Heterokonta Phytophthora infestans, independently expanded their HECT repertoire. In contrast, plant, excavate, rhodophyte, chlorophyte, and fungal genomes have a more limited enzymatic repertoire. Our genomic survey and phylogenetic analysis clarifies the origin and evolution of different HECT families among eukaryotes and provides a useful phylogenetic framework for future evolutionary studies of this regulatory pathway.}, } @article {pmid23562785, year = {2013}, author = {Premachandra, HK and De Zoysa, M and Nikapitiya, C and Lee, Y and Wickramaarachchi, WD and Whang, I and Lee, J}, title = {Molluskan fasciclin-1 domain-containing protein: molecular characterizationand gene expression analysis of fasciclin 1-like protein from disk abalone (Haliotis discus discus).}, journal = {Gene}, volume = {522}, number = {2}, pages = {219-225}, doi = {10.1016/j.gene.2013.03.053}, pmid = {23562785}, issn = {1879-0038}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Cell Adhesion ; Cell Adhesion Molecules, Neuronal/chemistry/*genetics/metabolism ; Cloning, Molecular ; Gastropoda/*genetics/immunology/metabolism/microbiology ; Gene Expression ; Hemocytes/metabolism ; Listeria monocytogenes ; Molecular Sequence Data ; Phylogeny ; RNA, Messenger/genetics/metabolism ; Sequence Analysis, DNA ; Vibrio parahaemolyticus/physiology ; }, abstract = {Cell-to-cell contacts play a key role in multicellular systems and organisms. Fasciclin-1 (FAS-1) is a lipid-linked membrane associated glycoprotein that is a member of a newly recognized family of cell adhesion molecules sharing features with the immunoglobulins, cadherins, integrins, and selectins. Here, we report the identification and molecular characterization of a novel FAS-1 domain-containing cDNA from disk abalone (Haliotis discus discus), including its gene expression profile and immune response to bacterial stimuli and tissue injuries. Designated as Abfac1, the 909bp open reading frame (ORF) encodes 303 amino acid (aa) residues with a predicted molecular mass of 33kDa and isoelectric (pI) value of 4.9. The aa sequence contains two FAS-1 domains and three conserved regions, FRa motif, H-box, and FRb motif. Phylogenetic analysis showed the closest relation to Jellyfish cell adhesion protein. In healthy abalone, Abfac1 expression is highest in hepatopancreas followed by mantle and lowest in digestive gland. In immune-stimulated abalones, relative Abfac1 mRNA expression was increased in hemocytes by ~11-fold at 48h after the Vibrio parahaemolyticus infection, by 3.1-fold at 6h after the Listeria monocytogenes infection and by ~9-fold at 6h after the LPS injection. Similarly, tissue injuries caused significant increase of relative mRNA expression by 3.5-fold in hemocytes and by ~10-fold in mantle at 12h post-injury. These results suggest that the novel member of the FAS-1 domain-containing protein family, Abfac1, may be involved in immune response and cell adhesion in disk abalone.}, } @article {pmid23556147, year = {2013}, author = {Tarakanov, AO and Fuxe, KG}, title = {Integrin triplets of marine sponges in the murine and human MHCI-CD8 interface and in the interface of human neural receptor heteromers and subunits.}, journal = {SpringerPlus}, volume = {2}, number = {1}, pages = {128}, pmid = {23556147}, issn = {2193-1801}, abstract = {Based on our theory, main triplets of amino acid residues have been discovered in cell-adhesion receptors (integrins) of marine sponges, which participate as homologies in the interface between two major immune molecules, MHC class I (MHCI) and CD8αβ. They appear as homologies also in several human neural receptor heteromers and subunits. The obtained results probably mean that neural and immune receptors also utilize these structural integrin triplets to form heteromers and ion channels, which are required for a tuned and integrated intracellular and intercellular communication and a communication between cells and the extracellular matrix with an origin in sponges, the oldest multicellular animals.}, } @article {pmid23551947, year = {2013}, author = {Sadrieh, A and Mann, SA and Subbiah, RN and Domanski, L and Taylor, JA and Vandenberg, JI and Hill, AP}, title = {Quantifying the origins of population variability in cardiac electrical activity through sensitivity analysis of the electrocardiogram.}, journal = {The Journal of physiology}, volume = {591}, number = {17}, pages = {4207-4222}, pmid = {23551947}, issn = {1469-7793}, mesh = {*Action Potentials ; Data Interpretation, Statistical ; Electrocardiography ; Heart/*physiology ; Heart Rate ; Humans ; Ion Transport ; *Models, Cardiovascular ; Myocytes, Cardiac/metabolism/physiology ; Potassium Channels/metabolism ; }, abstract = {Altered function of ion channels in the heart can increase the risk of sudden arrhythmic death. Hundreds of genetic variants exist in these cardiac ion channel genes. The challenge is how to interpret the effects of multiple conductance perturbations on the complex multi-variable cardiac electrical system? In theory, sensitivity analysis can address this question. However, to date this approach has been restricted by computational overheads to analysis of isolated cells, which has limited extrapolation to physiologically relevant scales. The goal of this study was to extend existing sensitivity analyses to electrocardiogram (ECG) signals derived from multicellular systems and quantify the contribution of ionic conductances to emergent properties of the ECG. To achieve this, we have developed a highly parallelised simulation environment using unconventional high performance computing architectures to analyse the emergent electrical properties of a multicellular system. This has permitted the first systematic analysis of the molecular basis of the T wave amplitude, revealing important but distinct roles for delayed rectifier and inward rectifier K(+) currents. In addition to quantifying how interactions between multiple ion channels influence ECG parameters we show that these sensitivities are dynamic functions of heart rate. This study provides a significant advance in our understanding both of how individual ion conductances define ECG signals and of epistatic modification of cardiac electrical phenotypes. The parallelised simulation environment we have developed removes the computational roadblock that has limited this approach and so provides the framework for future analysis of more complex tissue and whole organ systems.}, } @article {pmid23551562, year = {2013}, author = {Gardiner, J}, title = {The evolution and diversification of plant microtubule-associated proteins.}, journal = {The Plant journal : for cell and molecular biology}, volume = {75}, number = {2}, pages = {219-229}, doi = {10.1111/tpj.12189}, pmid = {23551562}, issn = {1365-313X}, mesh = {Animals ; Arabidopsis/genetics ; Bryopsida/genetics ; Chlamydomonas reinhardtii/genetics ; *Evolution, Molecular ; Genome, Plant ; Magnoliopsida/genetics ; Microtubule-Associated Proteins/genetics/metabolism/*physiology ; Microtubules/chemistry/metabolism ; Oryza/genetics ; Plant Proteins/*genetics ; }, abstract = {Plant evolution is marked by major advances in structural characteristics that facilitated the highly successful colonization of dry land. Underlying these advances is the evolution of genes encoding specialized proteins that form novel microtubular arrays of the cytoskeleton. This review investigates the evolution of plant families of microtubule-associated proteins (MAPs) through the recently sequenced genomes of Arabidopsis thaliana, Oryza sativa, Selaginella moellendorffii, Physcomitrella patens, Volvox carteri and Chlamydomonas reinhardtii. The families of MAPs examined are AIR9, CLASP, CRIPT, MAP18, MOR1, TON, EB1, AtMAP70, SPR2, SPR1, WVD2 and MAP65 families (abbreviations are defined in the footnote to Table 1). Conjectures are made regarding the evolution of MAPs in plants in relation to the evolution of multicellularity, oriented cell division and vasculature. Angiosperms in particular have high numbers of proteins that are involved in promotion of helical growth or its suppression, and novel plant microtubular structures may have acted as a catalyst for the development of novel plant MAPs. Comparisons of plant MAP gene families with those of animals show that animals may have more flexibility in the structure of their microtubule cytoskeletons than plants, but with both plants and animals possessing many MAP splice variants.}, } @article {pmid23510136, year = {2013}, author = {Hoekstra, LA and Montooth, KL}, title = {Inducing extra copies of the Hsp70 gene in Drosophila melanogaster increases energetic demand.}, journal = {BMC evolutionary biology}, volume = {13}, number = {}, pages = {68}, pmid = {23510136}, issn = {1471-2148}, mesh = {Animals ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/*genetics/growth & development/*metabolism ; Energy Metabolism/*genetics ; *Evolution, Molecular ; *Gene Dosage ; HSP70 Heat-Shock Proteins/*genetics/metabolism ; Larva/genetics/growth & development/metabolism ; Temperature ; }, abstract = {BACKGROUND: Mutations that increase gene expression are predicted to increase energy allocation to transcription, translation and protein function. Despite an appreciation that energetic tradeoffs may constrain adaptation, the energetic costs of increased gene expression are challenging to quantify and thus easily ignored when modeling the evolution of gene expression, particularly for multicellular organisms. Here we use the well-characterized, inducible heat-shock response to test whether expressing additional copies of the Hsp70 gene increases energetic demand in Drosophila melanogaster.

RESULTS: We measured metabolic rates of larvae with different copy numbers of the Hsp70 gene to quantify energy expenditure before, during, and after exposure to 36°C, a temperature known to induce robust expression of Hsp70. We observed a rise in metabolic rate within the first 30 minutes of 36°C exposure above and beyond the increase in routine metabolic rate at 36°C. The magnitude of this increase in metabolic rate was positively correlated with Hsp70 gene copy number and reflected an increase as great as 35% of the 22°C metabolic rate. Gene copy number also affected Hsp70 mRNA levels as early as 15 minutes after larvae were placed at 36°C, demonstrating that gene copy number affects transcript abundance on the same timescale as the metabolic effects that we observed. Inducing Hsp70 also had lasting physiological costs, as larvae had significantly depressed metabolic rate when returned to 22°C after induction.

CONCLUSIONS: Our results demonstrate both immediate and persistent energetic consequences of gene copy number in a multicellular organism. We discuss these consequences in the context of existing literature on the pleiotropic effects of variation in Hsp70 copy number, and argue that the increased energetic demand of expressing extra copies of Hsp70 may contribute to known tradeoffs in physiological performance of extra-copy larvae. Physiological costs of mutations that greatly increase gene expression, such as these, may constrain their utility for adaptive evolution.}, } @article {pmid23504484, year = {2013}, author = {Ciarletta, P and Ambrosi, D and Maugin, GA and Preziosi, L}, title = {Mechano-transduction in tumour growth modelling.}, journal = {The European physical journal. E, Soft matter}, volume = {36}, number = {3}, pages = {23}, pmid = {23504484}, issn = {1292-895X}, mesh = {Animals ; Cell Proliferation ; Humans ; *Mechanotransduction, Cellular ; *Models, Biological ; Neoplasms/*pathology ; Thermodynamics ; }, abstract = {The evolution of biological systems is strongly influenced by physical factors, such as applied forces, geometry or the stiffness of the micro-environment. Mechanical changes are particularly important in solid tumour development, as altered stromal-epithelial interactions can provoke a persistent increase in cytoskeletal tension, driving the gene expression of a malignant phenotype. In this work, we propose a novel multi-scale treatment of mechano-transduction in cancer growth. The avascular tumour is modelled as an expanding elastic spheroid, whilst growth may occur both as a volume increase and as a mass production within a cell rim. Considering the physical constraints of an outer healthy tissue, we derive the thermo-dynamical requirements for coupling growth rate, solid stress and diffusing biomolecules inside a heterogeneous tumour. The theoretical predictions successfully reproduce the stress-dependent growth curves observed by in vitro experiments on multicellular spheroids.}, } @article {pmid23503846, year = {2013}, author = {Collén, J and Porcel, B and Carré, W and Ball, SG and Chaparro, C and Tonon, T and Barbeyron, T and Michel, G and Noel, B and Valentin, K and Elias, M and Artiguenave, F and Arun, A and Aury, JM and Barbosa-Neto, JF and Bothwell, JH and Bouget, FY and Brillet, L and Cabello-Hurtado, F and Capella-Gutiérrez, S and Charrier, B and Cladière, L and Cock, JM and Coelho, SM and Colleoni, C and Czjzek, M and Da Silva, C and Delage, L and Denoeud, F and Deschamps, P and Dittami, SM and Gabaldón, T and Gachon, CM and Groisillier, A and Hervé, C and Jabbari, K and Katinka, M and Kloareg, B and Kowalczyk, N and Labadie, K and Leblanc, C and Lopez, PJ and McLachlan, DH and Meslet-Cladiere, L and Moustafa, A and Nehr, Z and Nyvall Collén, P and Panaud, O and Partensky, F and Poulain, J and Rensing, SA and Rousvoal, S and Samson, G and Symeonidi, A and Weissenbach, J and Zambounis, A and Wincker, P and Boyen, C}, title = {Genome structure and metabolic features in the red seaweed Chondrus crispus shed light on evolution of the Archaeplastida.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {13}, pages = {5247-5252}, pmid = {23503846}, issn = {1091-6490}, mesh = {Base Sequence ; Chondrus/*genetics ; *Evolution, Molecular ; *Genes, Plant ; MicroRNAs/genetics ; Molecular Sequence Data ; Plant Proteins/genetics ; RNA, Plant/genetics ; }, abstract = {Red seaweeds are key components of coastal ecosystems and are economically important as food and as a source of gelling agents, but their genes and genomes have received little attention. Here we report the sequencing of the 105-Mbp genome of the florideophyte Chondrus crispus (Irish moss) and the annotation of the 9,606 genes. The genome features an unusual structure characterized by gene-dense regions surrounded by repeat-rich regions dominated by transposable elements. Despite its fairly large size, this genome shows features typical of compact genomes, e.g., on average only 0.3 introns per gene, short introns, low median distance between genes, small gene families, and no indication of large-scale genome duplication. The genome also gives insights into the metabolism of marine red algae and adaptations to the marine environment, including genes related to halogen metabolism, oxylipins, and multicellularity (microRNA processing and transcription factors). Particularly interesting are features related to carbohydrate metabolism, which include a minimalistic gene set for starch biosynthesis, the presence of cellulose synthases acquired before the primary endosymbiosis showing the polyphyly of cellulose synthesis in Archaeplastida, and cellulases absent in terrestrial plants as well as the occurrence of a mannosylglycerate synthase potentially originating from a marine bacterium. To explain the observations on genome structure and gene content, we propose an evolutionary scenario involving an ancestral red alga that was driven by early ecological forces to lose genes, introns, and intergenetic DNA; this loss was followed by an expansion of genome size as a consequence of activity of transposable elements.}, } @article {pmid23499811, year = {2013}, author = {Mokhtar, M}, title = {Investigating the properties of bio-chemical networks of artificial organisms with opposing behaviours.}, journal = {Bio Systems}, volume = {112}, number = {2}, pages = {73-84}, doi = {10.1016/j.biosystems.2013.03.011}, pmid = {23499811}, issn = {1872-8324}, mesh = {Algorithms ; Animals ; Biological Evolution ; Cell Communication ; Eukaryotic Cells/*metabolism ; *Gene Regulatory Networks ; Homeostasis ; Humans ; *Metabolic Networks and Pathways ; Models, Biological ; Prokaryotic Cells/*metabolism ; Signal Transduction ; }, abstract = {Organisms, be it singled-celled organisms or multi-cellular organisms, are constantly faced with opposing objectives requiring different sets of behaviours. These behaviours can be classified into two, predatory behaviours or anti-prey behaviours, with one set of behaviours causing an opposite effect to the other. A healthy organism aims to achieve its equilibrium state or to be in homeostasis. Homeostasis is achieved when a balance between the two opposing behaviours is created and maintained. This raises some questions: is there an innate mechanism that encodes for these categories of behaviours? Is there also an innate mechanism(s) that resolves conflicts and allows switching between these two opposing behaviours? If we consider artificial organisms as single-celled organisms, how do the organisms' gene regulatory network, metabolic network and/or signalling network (their biochemical networks) maintain homeostasis of the organisms? This paper investigates the properties of the networks of best evolved artificial organisms, in order to help answer these questions, and guide the evolutionary development of controllers for artificial systems.}, } @article {pmid23496580, year = {2013}, author = {Requejo, RJ and Camacho, J}, title = {Scarcity may promote cooperation in populations of simple agents.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {87}, number = {2}, pages = {022819}, doi = {10.1103/PhysRevE.87.022819}, pmid = {23496580}, issn = {1550-2376}, mesh = {*Competitive Behavior ; Computer Simulation ; *Cooperative Behavior ; *Game Theory ; *Models, Theoretical ; *Population Dynamics ; }, abstract = {In the study of the evolution of cooperation, resource limitations are usually assumed just to provide a finite population size. Recently, however, it has been pointed out that resource limitation may also generate dynamical payoffs able to modify the original structure of the games. Here we study analytically a phase transition from a homogeneous population of defectors when resources are abundant to the survival of unconditional cooperators when resources reduce below a threshold. To this end, we introduce a model of simple agents, with no memory or ability of recognition, interacting in well-mixed populations. The result might shed light on the role played by resource constraints on the origin of multicellularity.}, } @article {pmid23494299, year = {2013}, author = {Schilde, C and Schaap, P}, title = {The Amoebozoa.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {983}, number = {}, pages = {1-15}, pmid = {23494299}, issn = {1940-6029}, support = {BB/G020426/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amoebozoa/classification/cytology/physiology ; Biological Evolution ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Dictyostelium/*cytology/physiology ; Morphogenesis ; Phylogeny ; Protozoan Proteins/metabolism ; Signal Transduction ; Spores, Protozoan/cytology/physiology ; }, abstract = {The model organism Dictyostelium discoideum is a member of the Amoebozoa, one of the six major -divisions of eukaryotes. Amoebozoa comprise a wide variety of amoeboid and flagellate organisms with single cells measuring from 5 μm to several meters across. They have adopted many different life styles and sexual behaviors and can live in all but the most extreme environments. This chapter provides an overview of Amoebozoan diversity and compares roads towards multicellularity within the Amoebozoa with inventions of multicellularity in other protist divisions. The chapter closes with a scenario for the evolution of Dictyostelid multicellularity from an Amoebozoan stress response.}, } @article {pmid23484080, year = {2013}, author = {Lim, JJ and Kim, HJ and Kim, KS and Hong, JY and Lee, DR}, title = {In vitro culture-induced pluripotency of human spermatogonial stem cells.}, journal = {BioMed research international}, volume = {2013}, number = {}, pages = {143028}, pmid = {23484080}, issn = {2314-6141}, mesh = {Animals ; Antigens, Differentiation/*biosynthesis ; Cells, Cultured ; Embryoid Bodies/cytology/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology/*metabolism ; Male ; Mice ; Mice, SCID ; Spermatogonia/cytology/*metabolism ; }, abstract = {Unipotent spermatogonial stem cells (SSCs) can be transformed into ESC-like cells that exhibit pluripotency in vitro. However, except for mouse models, their characterization and their origins have remained controversies in other models including humans. This controversy has arisen primarily from the lack of the direct induction of ESC-like cells from well-characterized SSCs. Thus, the aim of the present study was to find and characterize pluripotent human SSCs in in vitro cultures of characterized SSCs. Human testicular tissues were dissociated and plated onto gelatin/laminin-coated dishes to isolate SSCs. In the presence of growth factors SSCs formed multicellular clumps after 2-4 weeks of culture. At passages 1 and 5, the clumps were dissociated and were then analyzed using markers of pluripotent cells. The number of SSEA-4-positive cells was extremely low but increased gradually up to ~ 10% in the SSC clumps during culture. Most of the SSEA-4-negative cells expressed markers for SSCs, and some cells coexpressed markers of both pluripotent and germ cells. The pluripotent cells formed embryoid bodies and teratomas that contained derivatives of the three germ layers in SCID mice. These results suggest that the pluripotent cells present within the clumps were derived directly from SSCs during in vitro culture.}, } @article {pmid23481191, year = {2013}, author = {Hulpiau, P and Gul, IS and van Roy, F}, title = {New insights into the evolution of metazoan cadherins and catenins.}, journal = {Progress in molecular biology and translational science}, volume = {116}, number = {}, pages = {71-94}, doi = {10.1016/B978-0-12-394311-8.00004-2}, pmid = {23481191}, issn = {1878-0814}, mesh = {Animals ; *Biological Evolution ; Cadherins/*genetics/metabolism ; Catenins/*genetics/metabolism ; }, abstract = {E-Cadherin and β-catenin are the best studied representatives of the superfamilies of transmembrane cadherins and intracellular armadillo catenins, respectively. However, in over 600 million years of multicellular animal evolution, these two superfamilies have diversified remarkably both structurally and functionally. Although their basic building blocks, respectively, the cadherin repeat domain and the armadillo repeat domain, predate metazoans, the specific and complex domain compositions of the different family members and their functional roles in cell adhesion and signaling appear to be key features for the emergence of multicellular animal life. Basal animals such as placozoans and sponges have a limited number of distinct cadherins and catenins. The origin of vertebrates, in particular, coincided with a large increase in the number of cadherins and armadillo proteins, including modern "classical" cadherins, protocadherins, and plakophilins. Also, α-catenins increased. This chapter introduces the many different family members and describes the putative evolutionary relationships between them.}, } @article {pmid23471616, year = {2013}, author = {Römling, U and Galperin, MY and Gomelsky, M}, title = {Cyclic di-GMP: the first 25 years of a universal bacterial second messenger.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {77}, number = {1}, pages = {1-52}, pmid = {23471616}, issn = {1098-5557}, support = {//Intramural NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Bacteria/classification/genetics/metabolism/*pathogenicity ; *Bacterial Physiological Phenomena ; Cyclic GMP/*analogs & derivatives/chemistry/genetics/metabolism ; Eukaryotic Cells/metabolism/microbiology ; *Gene Expression Regulation, Bacterial ; Humans ; Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Second Messenger Systems/genetics/*physiology ; }, abstract = {Twenty-five years have passed since the discovery of cyclic dimeric (3'→5') GMP (cyclic di-GMP or c-di-GMP). From the relative obscurity of an allosteric activator of a bacterial cellulose synthase, c-di-GMP has emerged as one of the most common and important bacterial second messengers. Cyclic di-GMP has been shown to regulate biofilm formation, motility, virulence, the cell cycle, differentiation, and other processes. Most c-di-GMP-dependent signaling pathways control the ability of bacteria to interact with abiotic surfaces or with other bacterial and eukaryotic cells. Cyclic di-GMP plays key roles in lifestyle changes of many bacteria, including transition from the motile to the sessile state, which aids in the establishment of multicellular biofilm communities, and from the virulent state in acute infections to the less virulent but more resilient state characteristic of chronic infectious diseases. From a practical standpoint, modulating c-di-GMP signaling pathways in bacteria could represent a new way of controlling formation and dispersal of biofilms in medical and industrial settings. Cyclic di-GMP participates in interkingdom signaling. It is recognized by mammalian immune systems as a uniquely bacterial molecule and therefore is considered a promising vaccine adjuvant. The purpose of this review is not to overview the whole body of data in the burgeoning field of c-di-GMP-dependent signaling. Instead, we provide a historic perspective on the development of the field, emphasize common trends, and illustrate them with the best available examples. We also identify unresolved questions and highlight new directions in c-di-GMP research that will give us a deeper understanding of this truly universal bacterial second messenger.}, } @article {pmid23468928, year = {2013}, author = {Hamaji, T and Smith, DR and Noguchi, H and Toyoda, A and Suzuki, M and Kawai-Toyooka, H and Fujiyama, A and Nishii, I and Marriage, T and Olson, BJ and Nozaki, H}, title = {Mitochondrial and plastid genomes of the colonial green alga Gonium pectorale give insights into the origins of organelle DNA architecture within the volvocales.}, journal = {PloS one}, volume = {8}, number = {2}, pages = {e57177}, pmid = {23468928}, issn = {1932-6203}, mesh = {Chlorophyta/classification/*genetics ; Gene Order ; *Genome, Mitochondrial ; *Genome, Plastid ; Phylogeny ; Volvox/classification/genetics ; }, abstract = {Volvocalean green algae have among the most diverse mitochondrial and plastid DNAs (mtDNAs and ptDNAs) from the eukaryotic domain. However, nearly all of the organelle genome data from this group are restricted to unicellular species, like Chlamydomonas reinhardtii, and presently only one multicellular species, the ∼4,000-celled Volvox carteri, has had its organelle DNAs sequenced. The V. carteri organelle genomes are repeat rich, and the ptDNA is the largest plastome ever sequenced. Here, we present the complete mtDNA and ptDNA of the colonial volvocalean Gonium pectorale, which is comprised of ∼16 cells and occupies a phylogenetic position closer to that of V. carteri than C. reinhardtii within the volvocine line. The mtDNA and ptDNA of G. pectorale are circular-mapping AT-rich molecules with respective lengths and coding densities of 16 and 222.6 kilobases and 73 and 44%. They share some features with the organelle DNAs of V. carteri, including palindromic repeats within the plastid compartment, but show more similarities with those of C. reinhardtii, such as a compact mtDNA architecture and relatively low organelle DNA intron contents. Overall, the G. pectorale organelle genomes raise several interesting questions about the origin of linear mitochondrial chromosomes within the Volvocales and the relationship between multicellularity and organelle genome expansion.}, } @article {pmid23455615, year = {2013}, author = {Iida, H and Ota, S and Inouye, I}, title = {Cleavage, incomplete inversion, and cytoplasmic bridges in Gonium pectorale (Volvocales, Chlorophyta).}, journal = {Journal of plant research}, volume = {126}, number = {5}, pages = {699-707}, pmid = {23455615}, issn = {1618-0860}, mesh = {Biological Evolution ; *Cell Division ; Chlorophyta/*embryology/ultrastructure ; Cytoplasm/ultrastructure ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Species Specificity ; Time-Lapse Imaging ; }, abstract = {Multicellularity arose several times in evolution of eukaryotes. The volvocine algae have full range of colonial organization from unicellular to colonies, and thus these algae are well-known models for examining the evolution and mechanisms of multicellularity. Gonium pectorale is a multicellular species of Volvocales and is thought to be one of the first small colonial organisms among the volvocine algae. In these algae, a cytoplasmic bridge is one of the key traits that arose during the evolution of multicellularity. Here, we observed the inversion process and the cytoplasmic bridges in G. pectorale using time-lapse, fluorescence, and electron microscopy. The cytoplasmic bridges were located in the middle region of the cell in 2-, 4-, 8-, and 16-celled stages and in inversion stages. However, there were no cytoplasmic bridges in the mature adult stage. Cytoplasmic bridges and cortical microtubules in G. pectorale suggest that a mechanism of kinesin-microtubule machinery similar to that in other volvocine algae is responsible for inversion in this species.}, } @article {pmid23454078, year = {2013}, author = {Jeltsch, A}, title = {Oxygen, epigenetic signaling, and the evolution of early life.}, journal = {Trends in biochemical sciences}, volume = {38}, number = {4}, pages = {172-176}, doi = {10.1016/j.tibs.2013.02.001}, pmid = {23454078}, issn = {0968-0004}, mesh = {Animals ; Cell Differentiation ; DNA/*chemistry ; DNA Methylation ; *Epigenesis, Genetic ; *Evolution, Molecular ; Genomic Instability ; Origin of Life ; Oxygen/*chemistry ; Phylogeny ; *Signal Transduction ; }, abstract = {After approximately 3 billion years of unicellular life on Earth, multicellular animals appeared some 600 million years ago, followed by the rapid emergence of most animal phyla during the Cambrian radiation. This evolutionary jump was paralleled by an increase in atmospheric oxygen, which I propose allowed the generation of epigenetic signaling systems that are essential for cellular differentiation in animals. Epigenetic signaling is based on the reversible deposition of chemically stable marks in DNA and histone proteins, with methylation of cytosine and lysine residues, respectively, playing a central role. Recent evidence indicates that the removal of such methyl groups critically depends on oxygenases. Hence, reversible epigenetic systems could only appear after accumulation of oxygen in the atmosphere.}, } @article {pmid23449590, year = {2013}, author = {Sakakibara, K and Ando, S and Yip, HK and Tamada, Y and Hiwatashi, Y and Murata, T and Deguchi, H and Hasebe, M and Bowman, JL}, title = {KNOX2 genes regulate the haploid-to-diploid morphological transition in land plants.}, journal = {Science (New York, N.Y.)}, volume = {339}, number = {6123}, pages = {1067-1070}, doi = {10.1126/science.1230082}, pmid = {23449590}, issn = {1095-9203}, mesh = {Bryopsida/*anatomy & histology/genetics/*growth & development ; *Diploidy ; Gene Deletion ; Genes, Plant/*physiology ; Germ Cells, Plant/*growth & development ; *Haploidy ; Homeodomain Proteins/genetics/*physiology ; }, abstract = {Unlike animals, land plants undergo an alternation of generations, producing multicellular bodies in both haploid (1n: gametophyte) and diploid (2n: sporophyte) generations. Plant body plans in each generation are regulated by distinct developmental programs initiated at either meiosis or fertilization, respectively. In mosses, the haploid gametophyte generation is dominant, whereas in vascular plants-including ferns, gymnosperms, and angiosperms-the diploid sporophyte generation is dominant. Deletion of the class 2 KNOTTED1-LIKE HOMEOBOX (KNOX2) transcription factors in the moss Physcomitrella patens results in the development of gametophyte bodies from diploid embryos without meiosis. Thus, KNOX2 acts to prevent the haploid-specific body plan from developing in the diploid plant body, indicating a critical role for the evolution of KNOX2 in establishing an alternation of generations in land plants.}, } @article {pmid23448886, year = {2013}, author = {Solari, CA and Kessler, JO and Goldstein, RE}, title = {A general allometric and life-history model for cellular differentiation in the transition to multicellularity.}, journal = {The American naturalist}, volume = {181}, number = {3}, pages = {369-380}, doi = {10.1086/669151}, pmid = {23448886}, issn = {1537-5323}, support = {BB/F021844/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Body Size/physiology ; Cell Differentiation/*physiology ; Chlorophyta/*growth & development ; Fertility/physiology ; Genetic Fitness/genetics/*physiology ; Germ Cells/*cytology ; *Models, Biological ; Reproduction/genetics/physiology ; }, abstract = {The transition from unicellular, to colonial, to larger multicellular organisms has benefits, costs, and requirements. Here we present a model inspired by the volvocine green algae that explains the dynamics involved in the unicellular-multicellular transition using life-history theory and allometry. We model the two fitness components (fecundity and viability) and compare the fitness of hypothetical colonies of different sizes with varying degrees of cellular differentiation to understand the general principles that underlie the evolution of multicellularity. We argue that germ-soma separation may have evolved to counteract the increasing costs and requirements of larger multicellular colonies. The model shows that the cost of investing in soma decreases with size. For lineages such as the Volvocales, as reproduction costs increase with size for undifferentiated colonies, soma specialization benefits the colony indirectly by decreasing such costs and directly by helping reproductive cells acquire resources for their metabolic needs. Germ specialization is favored once soma evolves and takes care of vegetative functions. To illustrate the model, we use some allometric relationships measured in Volvocales. Our analysis shows that the cost of reproducing an increasingly larger group has likely played an important role in the transition to multicellularity and cellular differentiation.}, } @article {pmid23448685, year = {2013}, author = {Vreede, BM and Lynch, JA and Roth, S and Sucena, E}, title = {Co-option of a coordinate system defined by the EGFr and Dpp pathways in the evolution of a morphological novelty.}, journal = {EvoDevo}, volume = {4}, number = {1}, pages = {7}, pmid = {23448685}, issn = {2041-9139}, abstract = {BACKGROUND: Morphological innovation is an elusive and fascinating concept in evolutionary biology. A novel structure may open up an array of possibilities for adaptation, and thus is fundamental to the evolution of complex multicellular life. We use the respiratory appendages on the dorsal-anterior side of the Drosophila eggshell as a model system for morphological novelty. To study the co-option of genetic pathways in the evolution of this novelty we have compared oogenesis and eggshell patterning in Drosophila melanogaster with Ceratitis capitata, a dipteran whose eggs do not bear dorsal appendages.

RESULTS: During the final stages of oogenesis, the appendages are formed by specific groups of cells in the follicular epithelium of the egg chamber. These cells are defined via signaling activity of the Dpp and EGFr pathways, and we find that both pathways are active in C. capitata oogenesis. The transcription factor gene mirror is expressed downstream of EGFr activation in a dorsolateral domain in the D. melanogaster egg chamber, but could not be detected during C. capitata oogenesis. In D. melanogaster, mirror regulates the expression of two important genes: broad, which defines the appendage primordia, and pipe, involved in embryonic dorsoventral polarity. In C. capitata, broad remains expressed ubiquitously throughout the follicular epithelium, and is not restricted to the appendage primordia. Interestingly pipe expression did not differ between the two species.

CONCLUSIONS: Our analysis identifies both broad and mirror as important nodes that have been redeployed in the Drosophila egg chamber patterning network in the evolution of a morphologically novel feature. Further, our results show how pre-existing signals can provide an epithelium with a spatial coordinate system, which can be co-opted for novel patterns.}, } @article {pmid23444428, year = {2013}, author = {Lehner, J and Berendt, S and Dörsam, B and Pérez, R and Forchhammer, K and Maldener, I}, title = {Prokaryotic multicellularity: a nanopore array for bacterial cell communication.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {27}, number = {6}, pages = {2293-2300}, doi = {10.1096/fj.12-225854}, pmid = {23444428}, issn = {1530-6860}, mesh = {Amidohydrolases/genetics/physiology ; Bacterial Proteins/genetics/physiology ; Cell Wall/enzymology/ultrastructure ; Genes, Bacterial ; Green Fluorescent Proteins/genetics/metabolism ; Microbial Interactions/genetics/*physiology ; Microscopy, Electron, Transmission ; Mutation ; Nanopores/ultrastructure ; Nostoc/*cytology/genetics/*physiology ; Recombinant Fusion Proteins/genetics/metabolism ; }, abstract = {The transition from unicellular to multicellular life, which occurred several times during evolution, requires tight interaction and communication of neighboring cells. The multicellular cyanobacterium Nostoc punctiforme ATCC 29133 forms filaments of hundreds of interacting cells exchanging metabolites and signal molecules and is able to differentiate specialized cells in response to environmental stimuli. Mutation of cell wall amidase AmiC2 leads to a severe phenotype with formation of aberrant septa in the distorted filaments, which completely lack cell communication and potential for cell differentiation. Here we demonstrate the function of the amidase AmiC2 in formation of cell-joining structures. The AmiC2 protein localizes to the young septum between cells and shows bona fide amidase activity in vivo and in vitro. Vancomycin staining identified the overall septum morphology in living cells. By electron microscopy of isolated peptidoglycan sacculi, the submicroscopic structure of the cell junctions could be visualized, revealing a novel function for a cell wall amidase: AmiC2 drills holes into the cross-walls, forming an array of ~155 nanopores with a diameter of ~20 nm each. These nanopores seem to constitute a framework for cell-joining proteins, penetrating the cell wall. The entire array of junctional nanopores appears as a novel bacterial organelle, establishing multicellularity in a filamentous prokaryote.}, } @article {pmid23443991, year = {2013}, author = {Yafremava, LS and Wielgos, M and Thomas, S and Nasir, A and Wang, M and Mittenthal, JE and Caetano-Anollés, G}, title = {A general framework of persistence strategies for biological systems helps explain domains of life.}, journal = {Frontiers in genetics}, volume = {4}, number = {}, pages = {16}, pmid = {23443991}, issn = {1664-8021}, abstract = {The nature and cause of the division of organisms in superkingdoms is not fully understood. Assuming that environment shapes physiology, here we construct a novel theoretical framework that helps identify general patterns of organism persistence. This framework is based on Jacob von Uexküll's organism-centric view of the environment and James G. Miller's view of organisms as matter-energy-information processing molecular machines. Three concepts describe an organism's environmental niche: scope, umwelt, and gap. Scope denotes the entirety of environmental events and conditions to which the organism is exposed during its lifetime. Umwelt encompasses an organism's perception of these events. The gap is the organism's blind spot, the scope that is not covered by umwelt. These concepts bring organisms of different complexity to a common ecological denominator. Ecological and physiological data suggest organisms persist using three strategies: flexibility, robustness, and economy. All organisms use umwelt information to flexibly adapt to environmental change. They implement robustness against environmental perturbations within the gap generally through redundancy and reliability of internal constituents. Both flexibility and robustness improve survival. However, they also incur metabolic matter-energy processing costs, which otherwise could have been used for growth and reproduction. Lineages evolve unique tradeoff solutions among strategies in the space of what we call "a persistence triangle." Protein domain architecture and other evidence support the preferential use of flexibility and robustness properties. Archaea and Bacteria gravitate toward the triangle's economy vertex, with Archaea biased toward robustness. Eukarya trade economy for survivability. Protista occupy a saddle manifold separating akaryotes from multicellular organisms. Plants and the more flexible Fungi share an economic stratum, and Metazoa are locked in a positive feedback loop toward flexibility.}, } @article {pmid23441759, year = {2013}, author = {Xu, R and Rudd, TR and Hughes, AJ and Siligardi, G and Fernig, DG and Yates, EA}, title = {Analysis of the fibroblast growth factor receptor (FGFR) signalling network with heparin as coreceptor: evidence for the expansion of the core FGFR signalling network.}, journal = {The FEBS journal}, volume = {280}, number = {10}, pages = {2260-2270}, doi = {10.1111/febs.12201}, pmid = {23441759}, issn = {1742-4658}, mesh = {Binding Sites ; Circular Dichroism/methods ; Cloning, Molecular ; Evolution, Molecular ; Fibroblast Growth Factor 7/genetics/metabolism ; Fibroblast Growth Factors/genetics/*metabolism ; Genetic Vectors/genetics/metabolism ; Heparin/*metabolism ; Heparitin Sulfate/metabolism ; Humans ; Multiprotein Complexes/metabolism ; Protein Binding ; Protein Interaction Mapping/methods ; Protein Structure, Secondary ; Receptor, Fibroblast Growth Factor, Type 1/metabolism ; Receptor, Fibroblast Growth Factor, Type 2/*metabolism ; *Signal Transduction ; }, abstract = {The evolution of the fibroblast growth factor (FGF)-FGF receptor (FGFR) signalling system has closely followed that of multicellular organisms. The abilities of nine FGFs (FGF-1 to FGF-9; examples of FGF subfamilies 1, 4, 7, 8, and 9) and seven FGFRs or isoforms (FGFR1b, FGFR1c, FGFR2b, FGFR2c, FGFR3b, FGFR3c, and FGFR4) to support signalling in the presence of heparin, a proxy for the cellular heparan sulfate coreceptor, were assembled into a network. A connection between two FGFRs was defined as their mutual ability to signal with a particular FGF. The network contained a core of four receptors (FGFR1c, FGFR2c, FGFR3c, and FGFR4) with complete connectivity and high redundancy. Analysis of the wider network indicated that neither FGF-3 nor FGF-7 was well connected to this core of four receptors, and that divergence of a precursor of FGF subgroups 1, 4 and 9 from FGF subgroup 8 may have allowed expansion from a three-member FGFR core signalling system to the four-member core network. This increases by four-fold the number of possible signalling combinations. Synchrotron radiation CD spectra of the FGFs with heparin revealed no overall common structural change, suggesting the existence of distinct heparin-binding sites throughout the FGFs. The approach provides a potential method of identifying agents capable of influencing particular FGF-FGFR combinations, or areas of the signalling network, for experimental or therapeutic purposes.}, } @article {pmid23437009, year = {2013}, author = {Suvorova, ES and Croken, M and Kratzer, S and Ting, LM and Conde de Felipe, M and Balu, B and Markillie, ML and Weiss, LM and Kim, K and White, MW}, title = {Discovery of a splicing regulator required for cell cycle progression.}, journal = {PLoS genetics}, volume = {9}, number = {2}, pages = {e1003305}, pmid = {23437009}, issn = {1553-7404}, support = {AI93220/AI/NIAID NIH HHS/United States ; P30AI051519/AI/NIAID NIH HHS/United States ; RC4 AI092801/AI/NIAID NIH HHS/United States ; R01 AI089885/AI/NIAID NIH HHS/United States ; R01AI087625/AI/NIAID NIH HHS/United States ; R01 AI077662/AI/NIAID NIH HHS/United States ; R01 AI095094/AI/NIAID NIH HHS/United States ; P30 AI051519/AI/NIAID NIH HHS/United States ; 1S10RR019352/RR/NCRR NIH HHS/United States ; R01 AI087625/AI/NIAID NIH HHS/United States ; RC4AI092801/AI/NIAID NIH HHS/United States ; T32GM007491/GM/NIGMS NIH HHS/United States ; 1S10RR021056/RR/NCRR NIH HHS/United States ; R01AI077662/AI/NIAID NIH HHS/United States ; R56 AI093220/AI/NIAID NIH HHS/United States ; S10 RR019352/RR/NCRR NIH HHS/United States ; T32 GM007491/GM/NIGMS NIH HHS/United States ; R01AI095094/AI/NIAID NIH HHS/United States ; S10 RR021056/RR/NCRR NIH HHS/United States ; R01AI089885/AI/NIAID NIH HHS/United States ; }, mesh = {Alternative Splicing/*genetics ; Cell Cycle/*genetics ; Conserved Sequence/genetics ; G1 Phase/genetics ; Gene Expression Regulation ; Humans ; Mutation ; Nucleotide Motifs/genetics ; *RNA, Messenger/genetics/metabolism ; *RNA-Binding Proteins/genetics/metabolism ; Sequence Homology, Amino Acid ; Temperature ; *Toxoplasma/genetics/metabolism ; }, abstract = {In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.}, } @article {pmid23431170, year = {2013}, author = {Chang, H and Nathans, J}, title = {Responses of hair follicle-associated structures to loss of planar cell polarity signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {10}, pages = {E908-17}, pmid = {23431170}, issn = {1091-6490}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Body Patterning/physiology ; Cell Polarity/*physiology ; Female ; Frizzled Receptors/deficiency/genetics/physiology ; Hair Follicle/*cytology/growth & development/physiology ; Merkel Cells/physiology ; Mice ; Mice, Knockout ; Muscle, Smooth/cytology ; Nerve Endings/ultrastructure ; Pregnancy ; Sebaceous Glands/cytology ; Signal Transduction/physiology ; Skin/cytology/innervation ; }, abstract = {The mammalian hair follicle unit consists of a central follicle and a series of associated structures: sebaceous glands, arrector pili muscles, Merkel cells, and sensory nerve endings. The architecture of this multicellular structure is highly polarized with respect to the body axes. Previous work has implicated Frizzled6 (Fz6)-mediated planar cell polarity (PCP) signaling in the initial specification of hair follicle orientation. Here we investigate the origin of polarity information among structures within the hair follicle unit. Merkel cell clusters appear to have direct access to Fz6-based polarity information, and they lose polarity in the absence of Fz6. By contrast, the other follicle-associated structures likely derive some or all of their polarity cues from hair follicles, and as a result, their orientations closely match that of their associated follicle. These experiments reveal the interplay between global and local sources of polarity information for coordinating the spatial arrangement of diverse multicellular structures. They also highlight the utility of mammalian skin as a system for quantitative analyses of biological polarity.}, } @article {pmid23425690, year = {2013}, author = {Hsieh, JC and Van Den Berg, D and Kang, H and Hsieh, CL and Lieber, MR}, title = {Large chromosome deletions, duplications, and gene conversion events accumulate with age in normal human colon crypts.}, journal = {Aging cell}, volume = {12}, number = {2}, pages = {269-279}, pmid = {23425690}, issn = {1474-9726}, support = {R01 CA100504/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/*genetics/pathology ; *Chromosome Deletion ; *Chromosome Duplication ; Chromosomes ; Colon/*metabolism/pathology ; DNA Copy Number Variations ; DNA Methylation ; Female ; *Gene Conversion ; Genome, Human ; Humans ; Loss of Heterozygosity ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; }, abstract = {Little is known about the types and numbers of mutations that may accumulate in normal human cells with age. Such information would require obtaining enough DNA from a single cell to accurately carry out reliable analysis despite extensive amplification; and complete genomic coverage under these circumstances is difficult. We have compared colon crypts, which are putatively clonal and contain ~2000 cells each, to determine how much somatic genetic variation occurs in vivo (without ex vivo cell culturing). Using high-density SNP microarrays, we find that chromosome deletions, duplications, and gene conversions were significantly more frequent in colons from the older individuals. These changes affected lengths ranging from 73 kb to 46 Mb. Although detection requires progeny of a single mutant stem cell to reach niche dominance over neighboring stem cells, none of the deletions appear likely to confer a selective advantage. Mutations can become fixed randomly during stem cell evolution through neutral drift in normal human crypts. The fact that chromosomal changes are detected in individual crypts with increasing age suggests that either such changes accumulate with age or single stem cell dominance increases with age, and the former is more likely. This progressive genome-wide divergence of human somatic cells with age has implications for aging and disease in multicellular organisms.}, } @article {pmid23419129, year = {2013}, author = {Fairclough, SR and Chen, Z and Kramer, E and Zeng, Q and Young, S and Robertson, HM and Begovic, E and Richter, DJ and Russ, C and Westbrook, MJ and Manning, G and Lang, BF and Haas, B and Nusbaum, C and King, N}, title = {Premetazoan genome evolution and the regulation of cell differentiation in the choanoflagellate Salpingoeca rosetta.}, journal = {Genome biology}, volume = {14}, number = {2}, pages = {R15}, pmid = {23419129}, issn = {1474-760X}, support = {R01 GM089977/GM/NIGMS NIH HHS/United States ; U54HG003067/HG/NHGRI NIH HHS/United States ; T32 HG 00047/HG/NHGRI NIH HHS/United States ; R01 HG004164/HG/NHGRI NIH HHS/United States ; }, mesh = {Choanoflagellata/*genetics/physiology ; Cytokinesis/genetics ; *Evolution, Molecular ; *Genome, Protozoan ; Protozoan Proteins/genetics/metabolism ; Septins/genetics/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: Metazoan multicellularity is rooted in mechanisms of cell adhesion, signaling, and differentiation that first evolved in the progenitors of metazoans. To reconstruct the genome composition of metazoan ancestors, we sequenced the genome and transcriptome of the choanoflagellate Salpingoeca rosetta, a close relative of metazoans that forms rosette-shaped colonies of cells.

RESULTS: A comparison of the 55 Mb S. rosetta genome with genomes from diverse opisthokonts suggests that the origin of metazoans was preceded by a period of dynamic gene gain and loss. The S. rosetta genome encodes homologs of cell adhesion, neuropeptide, and glycosphingolipid metabolism genes previously found only in metazoans and expands the repertoire of genes inferred to have been present in the progenitors of metazoans and choanoflagellates. Transcriptome analysis revealed that all four S. rosetta septins are upregulated in colonies relative to single cells, suggesting that these conserved cytokinesis proteins may regulate incomplete cytokinesis during colony development. Furthermore, genes shared exclusively by metazoans and choanoflagellates were disproportionately upregulated in colonies and the single cells from which they develop.

CONCLUSIONS: The S. rosetta genome sequence refines the catalog of metazoan-specific genes while also extending the evolutionary history of certain gene families that are central to metazoan biology. Transcriptome data suggest that conserved cytokinesis genes, including septins, may contribute to S. rosetta colony formation and indicate that the initiation of colony development may preferentially draw upon genes shared with metazoans, while later stages of colony maturation are likely regulated by genes unique to S. rosetta.}, } @article {pmid23402598, year = {2013}, author = {Lerche, K and Hallmann, A}, title = {Stable nuclear transformation of Eudorina elegans.}, journal = {BMC biotechnology}, volume = {13}, number = {}, pages = {11}, pmid = {23402598}, issn = {1472-6750}, mesh = {Cell Nucleus/*metabolism ; Chlamydomonas reinhardtii/genetics ; Chlorophyta/genetics/*metabolism ; Genes, Reporter ; Genetic Engineering ; Kanamycin Kinase/genetics/metabolism ; Luciferases/genetics/metabolism ; Paromomycin/pharmacology ; Plasmids/genetics/metabolism ; Promoter Regions, Genetic ; Streptomyces/genetics ; Transformation, Genetic/drug effects ; Volvox/genetics ; }, abstract = {BACKGROUND: A fundamental step in evolution was the transition from unicellular to differentiated, multicellular organisms. Volvocine algae have been used for several decades as a model lineage to investigate the evolutionary aspects of multicellularity and cellular differentiation. There are two well-studied volvocine species, a unicellular alga (Chlamydomonas reinhardtii) and a multicellular alga with differentiated cell types (Volvox carteri). Species with intermediate characteristics also exist, which blur the boundaries between unicellularity and differentiated multicellularity. These species include the globular alga Eudorina elegans, which is composed of 16-32 cells. However, detailed molecular analyses of E. elegans require genetic manipulation. Unfortunately, genetic engineering has not yet been established for Eudorina, and only limited DNA and/or protein sequence information is available.

RESULTS: Here, we describe the stable nuclear transformation of E. elegans by particle bombardment using both a chimeric selectable marker and reporter genes from different heterologous sources. Transgenic algae resistant to paromomycin were achieved using the aminoglycoside 3'-phosphotransferase VIII (aphVIII) gene of Streptomyces rimosus, an actinobacterium, under the control of an artificial promoter consisting of two V. carteri promoters in tandem. Transformants exhibited an increase in resistance to paromomycin by up to 333-fold. Co-transformation with non-selectable plasmids was achieved with a rate of 50 - 100%. The luciferase (gluc) gene from the marine copepod Gaussia princeps, which previously was engineered to match the codon usage of C. reinhardtii, was used as a reporter gene. The expression of gluc was mediated by promoters from C. reinhardtii and V. carteri. Heterologous heat shock promoters induced an increase in luciferase activity (up to 600-fold) at elevated temperatures. Long-term stability and both constitutive and inducible expression of the co-bombarded gluc gene was demonstrated by transcription analysis and bioluminescence assays.

CONCLUSIONS: Heterologous flanking sequences, including promoters, work in E. elegans and permit both constitutive and inducible expression of heterologous genes. Stable nuclear transformation of E. elegans is now routine. Thus, we show that genetic engineering of a species is possible even without the resources of endogenous genes and promoters.}, } @article {pmid23398683, year = {2013}, author = {Schultheiss, KP and Craddock, BP and Tong, M and Seeliger, M and Miller, WT}, title = {Metazoan-like signaling in a unicellular receptor tyrosine kinase.}, journal = {BMC biochemistry}, volume = {14}, number = {}, pages = {4}, pmid = {23398683}, issn = {1471-2091}, support = {CA58530/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Cell Line ; Choanoflagellata/*enzymology/metabolism ; Mice ; Molecular Sequence Data ; Phosphorylation ; Protein Structure, Tertiary ; Protozoan Proteins/chemistry/genetics/*metabolism ; Receptor Protein-Tyrosine Kinases/chemistry/genetics/*metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; *Signal Transduction ; Transfection ; }, abstract = {BACKGROUND: Receptor tyrosine kinases (RTKs) are crucial components of signal transduction systems in multicellular animals. Surprisingly, numerous RTKs have been identified in the genomes of unicellular choanoflagellates and other protists. Here, we report the first biochemical study of a unicellular RTK, namely RTKB2 from Monosiga brevicollis.

RESULTS: We cloned, expressed, and purified the RTKB2 kinase, and showed that it is enzymatically active. The activity of RTKB2 is controlled by autophosphorylation, as in metazoan RTKs. RTKB2 possesses six copies of a unique domain (designated RM2) in its C-terminal tail. An isolated RM2 domain (or a synthetic peptide derived from the RM2 sequence) served as a substrate for RTKB2 kinase. When phosphorylated, the RM2 domain bound to the Src homology 2 domain of MbSrc1 from M. brevicollis. NMR structural studies of the RM2 domain indicated that it is disordered in solution.

CONCLUSIONS: Our results are consistent with a model in which RTKB2 activation stimulates receptor autophosphorylation within the RM2 domains. This leads to recruitment of Src-like kinases (and potentially other M. brevicollis proteins) and further phosphorylation, which may serve to increase or dampen downstream signals. Thus, crucial features of signal transduction circuitry were established prior to the evolution of metazoans from their unicellular ancestors.}, } @article {pmid23397797, year = {2012}, author = {Gilbert, SF and Sapp, J and Tauber, AI}, title = {A symbiotic view of life: we have never been individuals.}, journal = {The Quarterly review of biology}, volume = {87}, number = {4}, pages = {325-341}, doi = {10.1086/668166}, pmid = {23397797}, issn = {0033-5770}, mesh = {Animals ; Humans ; *Symbiosis ; }, abstract = {The notion of the "biological individual" is crucial to studies of genetics, immunology, evolution, development, anatomy, and physiology. Each of these biological subdisciplines has a specific conception of individuality, which has historically provided conceptual contexts for integrating newly acquired data. During the past decade, nucleic acid analysis, especially genomic sequencing and high-throughput RNA techniques, has challenged each of these disciplinary definitions by finding significant interactions of animals and plants with symbiotic microorganisms that disrupt the boundaries that heretofore had characterized the biological individual. Animals cannot be considered individuals by anatomical or physiological criteria because a diversity of symbionts are both present and functional in completing metabolic pathways and serving other physiological functions. Similarly, these new studies have shown that animal development is incomplete without symbionts. Symbionts also constitute a second mode of genetic inheritance, providing selectable genetic variation for natural selection. The immune system also develops, in part, in dialogue with symbionts and thereby functions as a mechanism for integrating microbes into the animal-cell community. Recognizing the "holobiont"--the multicellular eukaryote plus its colonies of persistent symbionts--as a critically important unit of anatomy, development, physiology, immunology, and evolution opens up new investigative avenues and conceptually challenges the ways in which the biological subdisciplines have heretofore characterized living entities.}, } @article {pmid23396676, year = {2013}, author = {Ewald, PW and Swain Ewald, HA}, title = {Toward a general evolutionary theory of oncogenesis.}, journal = {Evolutionary applications}, volume = {6}, number = {1}, pages = {70-81}, pmid = {23396676}, issn = {1752-4571}, abstract = {We propose an evolutionary framework, the barrier theory of cancer, which is based on the distinction between barriers to oncogenesis and restraints. Barriers are defined as mechanisms that prevent oncogenesis. Restraints, which are more numerous, inhibit but do not prevent oncogenesis. Processes that compromise barriers are essential causes of cancer; those that interfere with restraints are exacerbating causes. The barrier theory is built upon the three evolutionary processes involved in oncogenesis: natural selection acting on multicellular organisms to mold barriers and restraints, natural selection acting on infectious organisms to abrogate these protective mechanisms, and oncogenic selection which is responsible for the evolution of normal cells into cancerous cells. The barrier theory is presented as a first step toward the development of a general evolutionary theory of cancer. Its attributes and implications for intervention are compared with those of other major conceptual frameworks for understanding cancer: the clonal diversification model, the stem cell theory and the hallmarks of cancer. The barrier theory emphasizes the practical value of distinguishing between essential and exacerbating causes. It also stresses the importance of determining the scope of infectious causation of cancer, because individual pathogens can be responsible for multiple essential causes in infected cells.}, } @article {pmid23396311, year = {2013}, author = {Nunney, L}, title = {The real war on cancer: the evolutionary dynamics of cancer suppression.}, journal = {Evolutionary applications}, volume = {6}, number = {1}, pages = {11-19}, pmid = {23396311}, issn = {1752-4571}, abstract = {Cancer is a disease of multicellular animals caused by unregulated cell division. The prevailing model of cancer (multistage carcinogenesis) is based on the view that cancer results after a series of (generally somatic) mutations that knock out the genetic mechanisms suppressing unregulated cell growth. The chance of these mutations occurring increases with size and longevity, leading to Peto's paradox: why don't large animals have a higher lifetime incidence of cancer than small animals? The solution to this paradox is evolution. From an evolutionary perspective, an increasing frequency of prereproductive cancer deaths results in natural selection for enhanced cancer suppression. The expected result is a prereproductive risk of cancer across species that is independent of life history. However, within species, we still expect cancer risk to increase with size and longevity. Here, I review the evolutionary model of cancer suppression and some recent empirical evidence supporting it. Data from humans and domestic dogs confirm the expected intraspecific association between size and cancer risk, while results from interspecific comparisons between rodents provide the best evidence to date of the predicted recruitment of additional cancer suppression mechanisms as species become larger or longer lived.}, } @article {pmid23395845, year = {2014}, author = {Benito, N and Fernández-Ruiz, A and Makarov, VA and Makarova, J and Korovaichuk, A and Herreras, O}, title = {Spatial modules of coherent activity in pathway-specific LFPs in the hippocampus reflect topology and different modes of presynaptic synchronization.}, journal = {Cerebral cortex (New York, N.Y. : 1991)}, volume = {24}, number = {7}, pages = {1738-1752}, doi = {10.1093/cercor/bht022}, pmid = {23395845}, issn = {1460-2199}, mesh = {Animals ; Bicuculline/pharmacology ; Electric Stimulation ; Evoked Potentials/drug effects/*physiology ; Excitatory Amino Acid Antagonists/pharmacology ; Female ; Functional Laterality ; GABA-A Receptor Antagonists/pharmacology ; Hippocampus/*cytology/physiology ; *Models, Neurological ; Nerve Net/drug effects/*physiology ; Neurons/*cytology/drug effects/physiology ; Perforant Pathway/physiology ; Presynaptic Terminals/drug effects/*physiology ; Quinoxalines/pharmacology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Ongoing network activity often manifests as irregular fluctuations in local field potentials (LFPs), a complex mixture of multicellular synaptic currents of varying locations and extensions. Among other conditions, for synchronously firing presynaptic units to generate sizable postsynaptic LFPs, their axonal territories should overlap. We have taken advantage of anatomical regularity of the rat hippocampus and combined multiple linear recordings and spatial discrimination techniques to separate pathway-specific LFPs with enough spatial resolution to discriminate postsynaptic regions of varying activation, and to investigate their presynaptic origin, chemical nature, and spatial extension. We identified 6 main excitatory and inhibitory LFP generators with different synaptic territories in principal cells and hippocampal subfields matching anatomical pathways. Some recognized pathways did not contribute notably to LFPs. Each showed different septo-temporal spatial modules over which the field potential fluctuations were synchronous. These modules were explained by either the strong overlap of synaptic territories of coactivated afferent neurons (e.g., CA3 clusters for CA1 Schaffer LFPs), or widespread coalescence of postsynaptic territories (granule cell somatic inhibition). We also show evidence that distinct modes of afferent synchronization generate stereotyped spatial patterns of synchronous LFPs in one pathway. Thus, studying spatial coherence of pathway-specific LFPs provides remote access to the dynamics of afferent populations.}, } @article {pmid23393190, year = {2013}, author = {Sanges, R and Hadzhiev, Y and Gueroult-Bellone, M and Roure, A and Ferg, M and Meola, N and Amore, G and Basu, S and Brown, ER and De Simone, M and Petrera, F and Licastro, D and Strähle, U and Banfi, S and Lemaire, P and Birney, E and Müller, F and Stupka, E}, title = {Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development.}, journal = {Nucleic acids research}, volume = {41}, number = {6}, pages = {3600-3618}, pmid = {23393190}, issn = {1362-4962}, support = {TGM11SB2/TI_/Telethon/Italy ; }, mesh = {Animals ; Base Sequence ; Conserved Sequence ; Dogs ; *Enhancer Elements, Genetic ; Fishes/genetics ; *Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Genes, Homeobox ; Genetic Loci ; Genome ; Humans ; Mammals/genetics ; Mice ; Synteny ; Transcription, Genetic ; Urochordata/*genetics ; Vertebrates/*genetics ; }, abstract = {Co-option of cis-regulatory modules has been suggested as a mechanism for the evolution of expression sites during development. However, the extent and mechanisms involved in mobilization of cis-regulatory modules remains elusive. To trace the history of non-coding elements, which may represent candidate ancestral cis-regulatory modules affirmed during chordate evolution, we have searched for conserved elements in tunicate and vertebrate (Olfactores) genomes. We identified, for the first time, 183 non-coding sequences that are highly conserved between the two groups. Our results show that all but one element are conserved in non-syntenic regions between vertebrate and tunicate genomes, while being syntenic among vertebrates. Nevertheless, in all the groups, they are significantly associated with transcription factors showing specific functions fundamental to animal development, such as multicellular organism development and sequence-specific DNA binding. The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores. We refer to the elements as 'Olfactores conserved non-coding elements'.}, } @article {pmid23388496, year = {2013}, author = {Eickel, N and Kaiser, G and Prado, M and Burda, PC and Roelli, M and Stanway, RR and Heussler, VT}, title = {Features of autophagic cell death in Plasmodium liver-stage parasites.}, journal = {Autophagy}, volume = {9}, number = {4}, pages = {568-580}, pmid = {23388496}, issn = {1554-8635}, mesh = {Amino Acid Sequence ; Animals ; *Autophagy ; Conserved Sequence ; Databases, Protein ; Evolution, Molecular ; Gene Knockout Techniques ; Genetic Complementation Test ; Green Fluorescent Proteins/metabolism ; Hep G2 Cells ; Humans ; *Life Cycle Stages ; Lipid Metabolism ; Liver/*parasitology ; Mice ; Molecular Sequence Data ; Parasites/*cytology/*growth & development/ultrastructure ; Phagosomes/metabolism/ultrastructure ; Plasmodium berghei/*cytology/*growth & development/ultrastructure ; Protein Transport ; Protozoan Proteins/metabolism ; Saccharomyces cerevisiae/metabolism ; Schizonts/cytology/metabolism/ultrastructure ; Sequence Homology, Amino Acid ; Vacuoles/metabolism ; }, abstract = {Analyzing molecular determinants of Plasmodium parasite cell death is a promising approach for exploring new avenues in the fight against malaria. Three major forms of cell death (apoptosis, necrosis and autophagic cell death) have been described in multicellular organisms but which cell death processes exist in protozoa is still a matter of debate. Here we suggest that all three types of cell death occur in Plasmodium liver-stage parasites. Whereas typical molecular markers for apoptosis and necrosis have not been found in the genome of Plasmodium parasites, we identified genes coding for putative autophagy-marker proteins and thus concentrated on autophagic cell death. We characterized the Plasmodium berghei homolog of the prominent autophagy marker protein Atg8/LC3 and found that it localized to the apicoplast. A relocalization of PbAtg8 to autophagosome-like vesicles or vacuoles that appear in dying parasites was not, however, observed. This strongly suggests that the function of this protein in liver-stage parasites is restricted to apicoplast biology.}, } @article {pmid23386364, year = {2013}, author = {Caicci, F and Gasparini, F and Rigon, F and Zaniolo, G and Burighel, P and Manni, L}, title = {The oral sensory structures of Thaliacea (Tunicata) and consideration of the evolution of hair cells in Chordata.}, journal = {The Journal of comparative neurology}, volume = {521}, number = {12}, pages = {2756-2771}, doi = {10.1002/cne.23313}, pmid = {23386364}, issn = {1096-9861}, mesh = {Afferent Pathways/physiology ; Animals ; Axons/ultrastructure ; *Biological Evolution ; Chordata/*anatomy & histology ; Cilia/ultrastructure ; Hair Cells, Auditory/*physiology/ultrastructure ; Mechanoreceptors/*physiology/ultrastructure ; Microscopy, Electron ; Mouth/physiology ; Urochordata/*anatomy & histology ; }, abstract = {We analyzed the mouth of three species, representative of the three orders of the class Thaliacea (Tunicata)--Pyrosoma atlanticum (Pyrosomatida), Doliolum nationalis (Doliolida), and Thalia democratica (Salpida)--to verify the presence of mechanoreceptors, particularly hair cells. In vertebrates, hair cells are well-known mechanoreceptors of the inner ear and lateral line, typically exhibiting an apical hair bundle composed of a cilium and stereovilli but lacking an axon. For a long time, hair cells were thought to be exclusive to vertebrates. However, evidence of a mechanosensory organ (the coronal organ) employing hair cells in the mouth of tunicates, considered the sister group of vertebrates, suggests that tunicate and vertebrate hair cells may share a common origin. This study on thaliaceans, a tunicate group not yet investigated, shows that both P. atlanticum and D. nationalis possess a coronal organ, in addition to sensory structures containing peripheral neurons (i.e., cupular organs and triads of sensory cells). In contrast, in T. democratica, we did not recognize any oral multicellular sensory organ. We hypothesize that in T. democratica, hair cells were secondarily lost, concomitantly with the loss of branchial fissures, the acquisition of a feeding mechanism based on muscle activity, and a mechanosensory apparatus based on excitable epithelia. Our data are consistent with the hypothesis that hair cells were present in the common ancestor of tunicates and vertebrates, from which hair cells progressively evolved.}, } @article {pmid23385589, year = {2013}, author = {Niu, N and Liang, W and Yang, X and Jin, W and Wilson, ZA and Hu, J and Zhang, D}, title = {EAT1 promotes tapetal cell death by regulating aspartic proteases during male reproductive development in rice.}, journal = {Nature communications}, volume = {4}, number = {}, pages = {1445}, pmid = {23385589}, issn = {2041-1723}, mesh = {Amino Acid Sequence ; Aspartic Acid Proteases/*metabolism ; Base Sequence ; Basic Helix-Loop-Helix Transcription Factors/chemistry/genetics/metabolism ; Cell Death ; Chromosomes, Plant/genetics ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Models, Biological ; Molecular Sequence Data ; Mutation/genetics ; Organ Specificity ; Oryza/*cytology/*enzymology/genetics/ultrastructure ; Phenotype ; Phylogeny ; Physical Chromosome Mapping ; Plant Proteins/*chemistry/genetics/metabolism ; Pollen/*cytology/*enzymology/ultrastructure ; Protein Binding ; Reproduction ; Saccharomyces cerevisiae/cytology/metabolism ; }, abstract = {Programmed cell death is essential for the development of multicellular organisms, yet pathways of plant programmed cell death and its regulation remain elusive. Here we report that ETERNAL TAPETUM 1, a basic helix-loop-helix transcription factor conserved in land plants, positively regulates programmed cell death in tapetal cells in rice anthers. eat1 exhibits delayed tapetal cell death and aborted pollen formation. ETERNAL TAPETUM 1 directly regulates the expression of OsAP25 and OsAP37, which encode aspartic proteases that induce programmed cell death in both yeast and plants. Expression and genetic analyses revealed that ETERNAL TAPETUM 1 acts downstream of TAPETUM DEGENERATION RETARDATION, another positive regulator of tapetal programmed cell death, and that ETERNAL TAPETUM 1 can also interact with the TAPETUM DEGENERATION RETARDATION protein. This study demonstrates that ETERNAL TAPETUM 1 promotes aspartic proteases triggering plant programmed cell death, and reveals a dynamic regulatory cascade in male reproductive development in rice.}, } @article {pmid23383067, year = {2013}, author = {Senatore, A and Monteil, A and van Minnen, J and Smit, AB and Spafford, JD}, title = {NALCN ion channels have alternative selectivity filters resembling calcium channels or sodium channels.}, journal = {PloS one}, volume = {8}, number = {1}, pages = {e55088}, pmid = {23383067}, issn = {1932-6203}, mesh = {*Alternative Splicing ; Amino Acid Sequence ; Animals ; Calcium Channels/*chemistry/genetics ; Conserved Sequence ; Evolution, Molecular ; Gene Expression Regulation ; Humans ; Ion Channels ; Membrane Proteins ; Molecular Sequence Data ; Phylogeny ; Porosity ; Protein Isoforms/chemistry/genetics/metabolism ; Protein Structure, Tertiary ; Snails ; Sodium Channels/*chemistry/*genetics/metabolism ; }, abstract = {NALCN is a member of the family of ion channels with four homologous, repeat domains that include voltage-gated calcium and sodium channels. NALCN is a highly conserved gene from simple, extant multicellular organisms without nervous systems such as sponges and placozoans and mostly remains a single gene compared to the calcium and sodium channels which diversified into twenty genes in humans. The single NALCN gene has alternatively-spliced exons at exons 15 or exon 31 that splices in novel selectivity filter residues that resemble calcium channels (EEEE) or sodium channels (EKEE or EEKE). NALCN channels with alternative calcium, (EEEE) and sodium, (EKEE or EEKE) -selective pores are conserved in simple bilaterally symmetrical animals like flatworms to non-chordate deuterostomes. The single NALCN gene is limited as a sodium channel with a lysine (K)-containing pore in vertebrates, but originally NALCN was a calcium-like channel, and evolved to operate as both a calcium channel and sodium channel for different roles in many invertebrates. Expression patterns of NALCN-EKEE in pond snail, Lymnaea stagnalis suggest roles for NALCN in secretion, with an abundant expression in brain, and an up-regulation in secretory organs of sexually-mature adults such as albumen gland and prostate. NALCN-EEEE is equally abundant as NALCN-EKEE in snails, but is greater expressed in heart and other muscle tissue, and 50% less expressed in the brain than NALCN-EKEE. Transfected snail NALCN-EEEE and NALCN-EKEE channel isoforms express in HEK-293T cells. We were not able to distinguish potential NALCN currents from background, non-selective leak conductances in HEK293T cells. Native leak currents without expressing NALCN genes in HEK-293T cells are NMDG(+) impermeant and blockable with 10 µM Gd(3+) ions and are indistinguishable from the hallmark currents ascribed to mammalian NALCN currents expressed in vitro by Lu et al. in Cell. 2007 Apr 20;129(2):371-83.}, } @article {pmid23379554, year = {2013}, author = {Gusachenko, ON and Zenkova, MA and Vlassov, VV}, title = {Nucleic acids in exosomes: disease markers and intercellular communication molecules.}, journal = {Biochemistry. Biokhimiia}, volume = {78}, number = {1}, pages = {1-7}, doi = {10.1134/S000629791301001X}, pmid = {23379554}, issn = {1608-3040}, mesh = {Animals ; Biomarkers/analysis/metabolism ; Cell Adhesion Molecules/analysis/*metabolism ; Cell Communication ; Exosomes/*metabolism ; Humans ; Nucleic Acids/*metabolism ; }, abstract = {The term "exosomes" is currently used to describe specific vesicular structures of endosomal origin produced by the majority of eukaryotic cells. These natural vesicles have been under study for more than two decades. Nevertheless, a real splash of scientific interest in studies on exosomes took place only during recent years, when the concept of the role and functions of exosomes in multicellular organisms was essentially reconsidered. The major role in this was played by the discovery of exosomal mRNA and miRNA in 2007, which stimulated the idea of regulatory and communicative role of exosomes in the organism and also encouraged considering exosomes and other vesicles as potential biomarkers. The present review summarizes the up to date knowledge on the composition and probable physiological functions of nucleic acids released by different cells as components of exosomes. We also touch upon the problem of using these data in clinical diagnosis.}, } @article {pmid23378114, year = {2013}, author = {Kawaichi, S and Ito, N and Kamikawa, R and Sugawara, T and Yoshida, T and Sako, Y}, title = {Ardenticatena maritima gen. nov., sp. nov., a ferric iron- and nitrate-reducing bacterium of the phylum 'Chloroflexi' isolated from an iron-rich coastal hydrothermal field, and description of Ardenticatenia classis nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {63}, number = {Pt 8}, pages = {2992-3002}, doi = {10.1099/ijs.0.046532-0}, pmid = {23378114}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Chloroflexi/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/analysis ; Ferric Compounds/*metabolism ; Hydrogen-Ion Concentration ; Japan ; Molecular Sequence Data ; Nitrates/*metabolism ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sodium Chloride ; *Soil Microbiology ; Temperature ; Vitamin K 2/analysis ; }, abstract = {A novel thermophilic, chemoheterotrophic, Gram-negative-staining, multicellular filamentous bacterium, designated strain 110S(T), was isolated from an iron-rich coastal hydrothermal field in Japan. The isolate is facultatively aerobic and chemoheterotrophic. Phylogenetic analysis using 16S rRNA gene sequences nested strain 110S(T) in a novel class-level clone cluster of the phylum 'Chloroflexi'. The isolate grows by dissimilatory iron- and nitrate-reduction under anaerobic conditions, which is the first report of these abilities in the phylum 'Chloroflexi'. The organism is capable of growth with oxygen, ferric iron and nitrate as a possible electron acceptor, has a wide range of growth temperatures, and tolerates higher NaCl concentrations for growth compared to the other isolates in the phylum. Using phenotypic and phylogenetic data, strain 110S(T) (= JCM 17282(T) = NBRC 107679(T) = DSM 23922(T) = KCTC 23289(T) = ATCC BAA-2145(T)) is proposed as the type strain of a novel species in a new genus, Ardenticatena maritima gen. nov., sp. nov. In addition, as strain 110S(T) apparently constitutes a new class of the phylum 'Chloroflexi' with other related uncultivated clone sequences, we propose Ardenticatenia classis nov. and the subordinate taxa Ardenticatenales ord. nov. and Ardenticatenaceae fam. nov.}, } @article {pmid23375108, year = {2013}, author = {Clarke, M and Lohan, AJ and Liu, B and Lagkouvardos, I and Roy, S and Zafar, N and Bertelli, C and Schilde, C and Kianianmomeni, A and Bürglin, TR and Frech, C and Turcotte, B and Kopec, KO and Synnott, JM and Choo, C and Paponov, I and Finkler, A and Heng Tan, CS and Hutchins, AP and Weinmeier, T and Rattei, T and Chu, JS and Gimenez, G and Irimia, M and Rigden, DJ and Fitzpatrick, DA and Lorenzo-Morales, J and Bateman, A and Chiu, CH and Tang, P and Hegemann, P and Fromm, H and Raoult, D and Greub, G and Miranda-Saavedra, D and Chen, N and Nash, P and Ginger, ML and Horn, M and Schaap, P and Caler, L and Loftus, BJ}, title = {Genome of Acanthamoeba castellanii highlights extensive lateral gene transfer and early evolution of tyrosine kinase signaling.}, journal = {Genome biology}, volume = {14}, number = {2}, pages = {R11}, pmid = {23375108}, issn = {1474-760X}, support = {281633/ERC_/European Research Council/International ; BB/E016308/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Acanthamoeba castellanii/*genetics ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genome, Protozoan ; Introns ; Protein-Tyrosine Kinases/*genetics/metabolism ; Protozoan Proteins/*genetics/metabolism ; *Signal Transduction ; }, abstract = {BACKGROUND: The Amoebozoa constitute one of the primary divisions of eukaryotes, encompassing taxa of both biomedical and evolutionary importance, yet its genomic diversity remains largely unsampled. Here we present an analysis of a whole genome assembly of Acanthamoeba castellanii (Ac) the first representative from a solitary free-living amoebozoan.

RESULTS: Ac encodes 15,455 compact intron-rich genes, a significant number of which are predicted to have arisen through inter-kingdom lateral gene transfer (LGT). A majority of the LGT candidates have undergone a substantial degree of intronization and Ac appears to have incorporated them into established transcriptional programs. Ac manifests a complex signaling and cell communication repertoire, including a complete tyrosine kinase signaling toolkit and a comparable diversity of predicted extracellular receptors to that found in the facultatively multicellular dictyostelids. An important environmental host of a diverse range of bacteria and viruses, Ac utilizes a diverse repertoire of predicted pattern recognition receptors, many with predicted orthologous functions in the innate immune systems of higher organisms.

CONCLUSIONS: Our analysis highlights the important role of LGT in the biology of Ac and in the diversification of microbial eukaryotes. The early evolution of a key signaling facility implicated in the evolution of metazoan multicellularity strongly argues for its emergence early in the Unikont lineage. Overall, the availability of an Ac genome should aid in deciphering the biology of the Amoebozoa and facilitate functional genomic studies in this important model organism and environmental host.}, } @article {pmid23374161, year = {2013}, author = {Ng, TP and Saltin, SH and Davies, MS and Johannesson, K and Stafford, R and Williams, GA}, title = {Snails and their trails: the multiple functions of trail-following in gastropods.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {88}, number = {3}, pages = {683-700}, doi = {10.1111/brv.12023}, pmid = {23374161}, issn = {1469-185X}, mesh = {Animals ; Behavior, Animal/*physiology ; Gastropoda/*physiology ; Motor Activity/*physiology ; Mucus/*physiology ; }, abstract = {Snails are highly unusual among multicellular animals in that they move on a layer of costly mucus, leaving behind a trail that can be followed and utilized for various purposes by themselves or by other animals. Here we review more than 40 years of experimental and theoretical research to try to understand the ecological and evolutionary rationales for trail-following in gastropods. Data from over 30 genera are currently available, representing a broad taxonomic range living in both aquatic and terrestrial environments. The emerging picture is that the production of mucus trails, which initially was an adaptation to facilitate locomotion and/or habitat extension, has evolved to facilitate a multitude of additional functions. Trail-following supports homing behaviours, and provides simple mechanisms for self-organisation in groups of snails, promoting aggregation and thus relieving desiccation and predation pressures. In gastropods that copulate, trail-following is an important component in mate-searching, either as an alternative, or in addition to the release of water- or air-borne pheromones. In some species, this includes a capacity of males not only to identify trails of conspecifics but also to discriminate between trails laid by females and males. Notably, trail discrimination seems important as a pre-zygotic barrier to mating in some snail species. As production of a mucus trail is the most costly component of snail locomotion, it is also tempting to speculate that evolution has given rise to various ways to compensate for energy losses. Some snails, for example, increase energy intake by eating particles attached to the mucus of trails that they follow, whereas others save energy through reducing the production of their own mucus by moving over previously laid mucus trails. Trail-following to locate a prey item or a mate is also a way to save energy. While the rationale for trail-following in many cases appears clear, the basic mechanisms of trail discrimination, including the mechanisms by which many snails determine the polarity of the trail, are yet to be experimentally determined. Given the multiple functions of trail-following we propose that future studies should adopt an integrated approach, taking into account the possibility of the simultaneous occurrence of many selectively advantageous roles of trail-following behaviour in gastropods. We also believe that future opportunities to link phenotypic and genotypic traits will make possible a new generation of research projects in which gastropod trail-following, its multitude of functions and evolutionary trade-offs can be further elucidated.}, } @article {pmid23369575, year = {2013}, author = {Oczypok, EA and Oury, TD and Chu, CT}, title = {It's a cell-eat-cell world: autophagy and phagocytosis.}, journal = {The American journal of pathology}, volume = {182}, number = {3}, pages = {612-622}, pmid = {23369575}, issn = {1525-2191}, support = {R01 NS065789/NS/NINDS NIH HHS/United States ; HL095495/HL/NHLBI NIH HHS/United States ; NS065789/NS/NINDS NIH HHS/United States ; AG026389/AG/NIA NIH HHS/United States ; T32 HL094295/HL/NHLBI NIH HHS/United States ; NS059806/NS/NINDS NIH HHS/United States ; R56 NS065789/NS/NINDS NIH HHS/United States ; R01 AG026389/AG/NIA NIH HHS/United States ; R21 HL095495/HL/NHLBI NIH HHS/United States ; P01 NS059806/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Autophagy ; Cells/cytology/*metabolism ; Homeostasis ; Humans ; Models, Biological ; *Phagocytosis ; Reactive Oxygen Species/metabolism ; }, abstract = {The process of cellular eating, or the phagocytic swallowing of one cell by another, is an ancient manifestation of the struggle for life itself. Following the endosymbiotic origin of eukaryotic cells, increased cellular and then multicellular complexity was accompanied by the emergence of autophagic mechanisms for self-digestion. Heterophagy and autophagy function not only to protect the nutritive status of cells, but also as defensive responses against microbial pathogens externally or the ill effects of damaged proteins and organelles within. Because of the key roles played by phagocytosis and autophagy in a wide range of acute and chronic human diseases, pathologists have played similarly key roles in elucidating basic regulatory phases for both processes. Studies in diverse organ systems (including the brain, liver, kidney, lung, and muscle) have defined key roles for these lysosomal pathways in infection control, cell death, inflammation, cancer, neurodegeneration, and mitochondrial homeostasis. The literature reviewed here exemplifies the role of pathology in defining leading-edge questions for continued molecular and pathophysiological investigations into all forms of cellular digestion.}, } @article {pmid23363998, year = {2012}, author = {Zhong, M and Kawaguchi, R and Kassai, M and Sun, H}, title = {Retina, retinol, retinal and the natural history of vitamin A as a light sensor.}, journal = {Nutrients}, volume = {4}, number = {12}, pages = {2069-2096}, pmid = {23363998}, issn = {2072-6643}, support = {R01 EY018144/EY/NEI NIH HHS/United States ; R01EY018144/EY/NEI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Biological Transport ; Humans ; *Light ; Opsins/*metabolism ; Receptors, G-Protein-Coupled/metabolism ; Retina/*physiology ; Retinaldehyde/*physiology ; Vision, Ocular/*physiology ; Vitamin A/*physiology ; }, abstract = {Light is both the ultimate energy source for most organisms and a rich information source. Vitamin A-based chromophore was initially used in harvesting light energy, but has become the most widely used light sensor throughout evolution from unicellular to multicellular organisms. Vitamin A-based photoreceptor proteins are called opsins and have been used for billions of years for sensing light for vision or the equivalent of vision. All vitamin A-based light sensors for vision in the animal kingdom are G-protein coupled receptors, while those in unicellular organisms are light-gated channels. This first major switch in evolution was followed by two other major changes: the switch from bistable to monostable pigments for vision and the expansion of vitamin A's biological functions. Vitamin A's new functions such as regulating cell growth and differentiation from embryogenesis to adult are associated with increased toxicity with its random diffusion. In contrast to bistable pigments which can be regenerated by light, monostable pigments depend on complex enzymatic cycles for regeneration after every photoisomerization event. Here we discuss vitamin A functions and transport in the context of the natural history of vitamin A-based light sensors and propose that the expanding functions of vitamin A and the choice of monostable pigments are the likely evolutionary driving forces for precise, efficient, and sustained vitamin A transport.}, } @article {pmid23362301, year = {2013}, author = {Niklas, KJ}, title = {Biophysical and size-dependent perspectives on plant evolution.}, journal = {Journal of experimental botany}, volume = {64}, number = {15}, pages = {4817-4827}, doi = {10.1093/jxb/ers379}, pmid = {23362301}, issn = {1460-2431}, mesh = {*Biological Evolution ; Biomechanical Phenomena ; *Biophysics ; Ecosystem ; Embryophyta/anatomy & histology/genetics ; Fossils ; Phenotype ; Plants/*anatomy & histology/genetics ; }, abstract = {Physical laws and processes have profoundly influenced plant evolution. Their effects are invariably size dependent and thus subject to scaling as well as biophysical analyses even though these effects differ depending upon the fluid (water or air) in which plants evolve. Although organisms cannot obviate the effects of physical laws and processes, the consequences of these effects can be altered by ontogenetic or phylogenetic alterations in geometry, shape, or orientation as well as in body size. These assertions are examined using theoretical insights and empirical data drawn from extant and fossil plants pertinent to four evolutionary transitions: (1) the evolution of multicellularity, (2) the transition from an aquatic to an aerial habitat, (3) the evolution of vascular tissues, and (4) the evolution of secondary growth by the independent acquisition of cambia. This examination shows how physical laws limit phenotypic expression, but how they also simultaneously provide alternative, potentially adaptive possibilities.}, } @article {pmid23360999, year = {2013}, author = {Ringrose, JH and van den Toorn, HW and Eitel, M and Post, H and Neerincx, P and Schierwater, B and Altelaar, AF and Heck, AJ}, title = {Deep proteome profiling of Trichoplax adhaerens reveals remarkable features at the origin of metazoan multicellularity.}, journal = {Nature communications}, volume = {4}, number = {}, pages = {1408}, pmid = {23360999}, issn = {2041-1723}, mesh = {Animals ; *Biological Evolution ; Databases, Protein ; Ion Exchange ; Phosphorylation ; Phosphotransferases/metabolism ; Phosphotyrosine/metabolism ; Placozoa/*cytology/*metabolism ; Protein Processing, Post-Translational ; Proteome/*metabolism ; Proteomics/*methods ; Receptors, Notch/metabolism ; Signal Transduction ; }, abstract = {Genome sequencing of arguably the simplest known animal, Trichoplax adhaerens, uncovered a rich array of transcription factor and signalling pathway genes. Although the existence of such genes allows speculation about the presence of complex regulatory events, it does not reveal the level of actual protein expression and functionalization through posttranslational modifications. Using high-resolution mass spectrometry, we here semi-quantify 6,516 predicted proteins, revealing evidence of horizontal gene transfer and the presence at the protein level of nodes important in animal signalling pathways. Moreover, our data demonstrate a remarkably high activity of tyrosine phosphorylation, in line with the hypothesized burst of tyrosine-regulated signalling at the instance of animal multicellularity. Together, this Trichoplax proteomics data set offers significant new insight into the mechanisms underlying the emergence of metazoan multicellularity and provides a resource for interested researchers.}, } @article {pmid23355006, year = {2013}, author = {Schmith, A and Groth, M and Ratka, J and Gatz, S and Spaller, T and Siol, O and Glöckner, G and Winckler, T}, title = {Conserved gene regulatory function of the carboxy-terminal domain of dictyostelid C-module-binding factor.}, journal = {Eukaryotic cell}, volume = {12}, number = {3}, pages = {460-468}, pmid = {23355006}, issn = {1535-9786}, mesh = {Base Sequence ; Conserved Sequence ; Dictyostelium/*genetics/metabolism ; Gene Expression Regulation ; Genes, Protozoan ; Molecular Sequence Data ; Mutation ; Phylogeny ; Protein Structure, Tertiary ; Protozoan Proteins/*chemistry/genetics/*metabolism ; Sequence Analysis, RNA ; Transcription Factors/*chemistry/genetics/*metabolism ; Transcription, Genetic ; Transcriptome ; }, abstract = {C-module-binding factor A (CbfA) is a jumonji-type transcription regulator that is important for maintaining the expression and mobility of the retrotransposable element TRE5-A in the social amoeba Dictyostelium discoideum. CbfA-deficient cells have lost TRE5-A retrotransposition, are impaired in the ability to feed on bacteria, and do not enter multicellular development because of a block in cell aggregation. In this study, we performed Illumina RNA-seq of growing CbfA mutant cells to obtain a list of CbfA-regulated genes. We demonstrate that the carboxy-terminal domain of CbfA alone is sufficient to mediate most CbfA-dependent gene expression. The carboxy-terminal domain of CbfA from the distantly related social amoeba Polysphondylium pallidum restored the expression of CbfA-dependent genes in the D. discoideum CbfA mutant, indicating a deep conservation in the gene regulatory function of this domain in the dictyostelid clade. The CbfA-like protein CbfB displays ∼25% sequence identity with CbfA in the amino-terminal region, which contains a JmjC domain and two zinc finger regions and is thought to mediate chromatin-remodeling activity. In contrast to CbfA proteins, where the carboxy-terminal domains are strictly conserved in all dictyostelids, CbfB proteins have completely unrelated carboxy-terminal domains. Outside the dictyostelid clade, CbfA-like proteins with the CbfA-archetypical JmjC/zinc finger arrangement and individual carboxy-terminal domains are prominent in filamentous fungi but are not found in yeasts, plants, and metazoans. Our data suggest that two functional regions of the CbfA-like proteins evolved at different rates to allow the occurrence of species-specific adaptation processes during genome evolution.}, } @article {pmid23352078, year = {2013}, author = {Marshall, WL and Berbee, ML}, title = {Comparative morphology and genealogical delimitation of cryptic species of sympatric isolates of Sphaeroforma (Ichthyosporea, Opisthokonta).}, journal = {Protist}, volume = {164}, number = {2}, pages = {287-311}, doi = {10.1016/j.protis.2012.12.002}, pmid = {23352078}, issn = {1618-0941}, mesh = {Animals ; Cell Wall/ultrastructure ; Cluster Analysis ; DNA, Protozoan/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; DNA, Ribosomal Spacer/chemistry/genetics ; Mesomycetozoea/*classification/*cytology/genetics ; Microscopy ; Molecular Sequence Data ; Organelles/ultrastructure ; Phylogeny ; RNA, Protozoan/genetics ; Sequence Analysis, DNA ; Spores, Protozoan/cytology ; }, abstract = {Of the ancient clades of unicellular relatives of the multicellular animals, ichthyosporea are among the easiest to collect, cultivate, and analyze at the population level. Once identified, species can be correlated with their animal hosts and geographical ranges. However, the spherical stages common to many ichthyosporea provide little basis for morphological species identification. This study of the genus Sphaeroforma is the first to apply patterns of genetic discontinuity to delimit species among any of the unicellular 'holozoa.' Sequences of three loci from 148 sympatric isolates, along with type cultures, provided concordant support for new species "Sphaeroforma nootkatensis" and "Sphaeroforma gastrica," and for formally describing 'Pseudoperkinsus tapetis,' as "Sphaeroforma tapetis". We document light and electron microscopic characters that distinguish the genus but not its species. "S. tapetis" sometimes had brief amoeboid or plasmodial motile stages and endospore release through pores. Unlike closely related Creolimax, Sphaeroforma lacked a central vacuole but had multiple peripheral nucleoli. Like distantly related eccrinales, Sphaeroforma cell walls had pores and a calyx. Analyses of allele frequencies in "S. tapetis" indicated geographical differentiation but no host specificity. Accurate molecular identification of species will increase the feasibility and reliability of further studies of Sphaeroforma in its natural habit.}, } @article {pmid23349899, year = {2013}, author = {Szczesny, P and Mykowiecka, A and Pawłowski, K and Grynberg, M}, title = {Distinct protein classes in human red cell proteome revealed by similarity of phylogenetic profiles.}, journal = {PloS one}, volume = {8}, number = {1}, pages = {e54471}, pmid = {23349899}, issn = {1932-6203}, mesh = {Bacteria ; Erythrocytes/*chemistry ; Eukaryotic Cells ; Evolution, Molecular ; Humans ; *Phylogeny ; Proteins/*classification/isolation & purification ; *Proteome ; }, abstract = {The minimal set of proteins necessary to maintain a vertebrate cell forms an interesting core of cellular machinery. The known proteome of human red blood cell consists of about 1400 proteins. We treated this protein complement of one of the simplest human cells as a model and asked the questions on its function and origins. The proteome was mapped onto phylogenetic profiles, i.e. vectors of species possessing homologues of human proteins. A novel clustering approach was devised, utilising similarity in the phylogenetic spread of homologues as distance measure. The clustering based on phylogenetic profiles yielded several distinct protein classes differing in phylogenetic taxonomic spread, presumed evolutionary history and functional properties. Notably, small clusters of proteins common to vertebrates or Metazoa and other multicellular eukaryotes involve biological functions specific to multicellular organisms, such as apoptosis or cell-cell signaling, respectively. Also, a eukaryote-specific cluster is identified, featuring GTP-ase signalling and ubiquitination. Another cluster, made up of proteins found in most organisms, including bacteria and archaea, involves basic molecular functions such as oxidation-reduction and glycolysis. Approximately one third of erythrocyte proteins do not fall in any of the clusters, reflecting the complexity of protein evolution in comparison to our simple model. Basically, the clustering obtained divides the proteome into old and new parts, the former originating from bacterial ancestors, the latter from inventions within multicellular eukaryotes. Thus, the model human cell proteome appears to be made up of protein sets distinct in their history and biological roles. The current work shows that phylogenetic profiles concept allows protein clustering in a way relevant both to biological function and evolutionary history.}, } @article {pmid23349118, year = {2013}, author = {Beall, CM}, title = {Human adaptability studies at high altitude: research designs and major concepts during fifty years of discovery.}, journal = {American journal of human biology : the official journal of the Human Biology Council}, volume = {25}, number = {2}, pages = {141-147}, doi = {10.1002/ajhb.22355}, pmid = {23349118}, issn = {1520-6300}, mesh = {*Acclimatization ; Adaptation, Physiological ; Altitude ; *Biological Evolution ; Cold Temperature ; Humans ; Oxygen/*metabolism ; Research Design ; }, abstract = {OBJECTIVES: This report presents a perspective on the broad research trends in the biology of human populations at high-altitude and their contributions to the improved understanding of evolution and adaptation. A focus is on the research that has occurred over the past 50 years of anthropological fieldwork on the Andean, Tibetan, and, to a lesser extent, the East African plateaus.

METHODS: With an emphasis on fieldwork studies, this report presents and illustrates major concepts and research designs in published high-altitude studies.

RESULTS: Early use of a single population-multiple stress research design focused on Andean Quechua, sometimes in comparison with European or admixed Andean-European samples. That design identified physical and sociocultural environmental factors including cold and under nutrition as well as high-altitude hypobaric hypoxia. Researchers accumulated evidence supporting the hypothesis of four modes of adaptation to a complex Andean highland environment: cultural, acclimatization, developmental, and genetic. The discovery that Andean biological patterns were not replicated among Tibetan highlanders stimulated research on the extent and origins of the contrasts. It also shifted emphasis to a multiple population - single stress study design. The discovery of oxygen-homeostasis-associated genetic loci and traits in all multicellular animals has transformed high-altitude research. Paradoxically, genomic analyses identifying the pertinent biological pathways are likely to return interest to environmental factors other than hypoxia.

CONCLUSIONS: Details of the proximate mechanisms, the biochemical, and physiological processes underlying the three modes of biological adaptation are accumulating. Better understanding of oxygen-homeostasis processes leads to questions about crossadaptation with other environmental factors. The particulars of the ultimate mechanisms, the evolutionary, and microevolutionary history underlying the population differences are also emerging. For example, similar hemoglobin phenotypes among Tibetan and Ethiopian Amhara highlanders associate with different genetic loci and the variants at those loci are present in most populations regardless of altitude. Continuing fieldwork is urgent because modernization and migration are changing the traditional ways of life and patterns of exposure to the environment among highlanders everywhere.}, } @article {pmid23335919, year = {2012}, author = {Amaral-Zettler, LA}, title = {Eukaryotic diversity at pH extremes.}, journal = {Frontiers in microbiology}, volume = {3}, number = {}, pages = {441}, pmid = {23335919}, issn = {1664-302X}, abstract = {Extremely acidic (pH < 3) and extremely alkaline (pH > 9) environments support a diversity of single-cell and to a lesser extent, multicellular eukaryotic life. This study compared alpha and beta diversity in eukaryotic communities from seven diverse aquatic environments with pH values ranging from 2 to 11 using massively-parallel pyrotag sequencing targeting the V9 hypervariable region of the 18S ribosomal RNA (rRNA) gene. A total of 946 operational taxonomic units (OTUs) were recovered at a 6% cut-off level (94% similarity) across the sampled environments. Hierarchical clustering of the samples segregated the communities into acidic and alkaline groups. Similarity percentage (SIMPER) analysis followed by indicator OTU analysis (IOA) and non-metric multidimensional scaling (NMDS) were used to determine which characteristic groups of eukaryotic taxa typify acidic or alkaline extremes and the extent to which pH explains eukaryotic community structure in these environments. Spain's Rio Tinto yielded the fewest observed OTUs while Nebraska Sandhills alkaline lakes yielded the most. Distinct OTUs, including metazoan OTUs, numerically dominated pH extreme sites. Indicator OTUs included the diatom Pinnularia and unidentified opisthokonts (Fungi and Filasterea) in the extremely acidic environments, and the ciliate Frontonia across the extremely alkaline sites. Inferred from NMDS, pH explained only a modest fraction of the variation across the datasets, indicating that other factors influence the underlying community structure in these environments. The findings from this study suggest that the ability for eukaryotes to adapt to pH extremes over a broad range of values may be rare, but further study of taxa that can broadly adapt across diverse acidic and alkaline environments, respectively present good models for understanding adaptation and should be targeted for future investigations.}, } @article {pmid23333946, year = {2013}, author = {Suga, H and Ruiz-Trillo, I}, title = {Development of ichthyosporeans sheds light on the origin of metazoan multicellularity.}, journal = {Developmental biology}, volume = {377}, number = {1}, pages = {284-292}, pmid = {23333946}, issn = {1095-564X}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Animals ; Animals, Genetically Modified ; Base Sequence ; *Biological Evolution ; Cell Nucleus Division/drug effects ; Eukaryota/*cytology/drug effects/genetics/*growth & development/ultrastructure ; Giant Cells/cytology/drug effects ; Models, Biological ; Molecular Sequence Data ; Morpholinos/pharmacology ; RNA Interference/drug effects ; Transformation, Genetic/drug effects ; }, abstract = {To understand the mechanisms involved in the transition from protists to multicellular animals (metazoans), studying unicellular relatives of metazoans is as important as studying metazoans themselves. However, investigations remain poor on the closest unicellular (or colonial) relatives of Metazoa, i.e., choanoflagellates, filastereans and ichthyosporeans. Molecular-level analyses on these protists have been severely limited by the lack of transgenesis tools. Their genomes, however, contain several key genes encoding proteins important for metazoan development and multicellularity, including those involved in cell-cell communication, cell proliferation, cell differentiation, and tissue growth control. Tools to analyze their functions in a molecular level are awaited. Here we report techniques of cell transformation and gene silencing developed for the first time in a close relative of metazoans, the ichthyosporean Creolimax fragrantissima. We propose C. fragrantissima as a model organism to investigate the origin of metazoan multicellularity. By transgenesis, we demonstrate that its colony develops from a fully-grown multinucleate syncytium, in which nuclear divisions are strictly synchronized. It has been hypothesized that metazoan multicellular development initially occurred in the course of evolution through successive rounds of cell division, which were not necessarily be synchronized, or alternatively through cell aggregation. Our findings point to another possible mechanism for the evolution of animal multicellularity, namely, cellularization of a syncytium in which nuclear divisions are synchronized. We believe that further studies on the development of ichthyosporeans by the use of our methodologies will provide novel insights into the origin of metazoan multicellularity.}, } @article {pmid23331916, year = {2013}, author = {Niklas, KJ and Newman, SA}, title = {The origins of multicellular organisms.}, journal = {Evolution & development}, volume = {15}, number = {1}, pages = {41-52}, doi = {10.1111/ede.12013}, pmid = {23331916}, issn = {1525-142X}, mesh = {Animals ; *Biological Evolution ; Body Patterning ; Cell Communication ; Cell Differentiation ; Cell Lineage ; Chlamydomonas/physiology ; Chlorophyta/physiology ; Developmental Biology ; Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Genome ; Genotype ; Phylogeny ; Species Specificity ; }, abstract = {Multicellularity has evolved in several eukaryotic lineages leading to plants, fungi, and animals. Theoretically, in each case, this involved (1) cell-to-cell adhesion with an alignment-of-fitness among cells, (2) cell-to-cell communication, cooperation, and specialization with an export-of-fitness to a multicellular organism, and (3) in some cases, a transition from "simple" to "complex" multicellularity. When mapped onto a matrix of morphologies based on developmental and physical rules for plants, these three phases help to identify a "unicellular ⇒ colonial ⇒ filamentous (unbranched ⇒ branched) ⇒ pseudoparenchymatous ⇒ parenchymatous" morphological transformation series that is consistent with trends observed within each of the three major plant clades. In contrast, a more direct "unicellular ⇒ colonial or siphonous ⇒ parenchymatous" series is observed in fungal and animal lineages. In these contexts, we discuss the roles played by the cooptation, expansion, and subsequent diversification of ancestral genomic toolkits and patterning modules during the evolution of multicellularity. We conclude that the extent to which multicellularity is achieved using the same toolkits and modules (and thus the extent to which multicellularity is homologous among different organisms) differs among clades and even among some closely related lineages.}, } @article {pmid23329689, year = {2013}, author = {Tian, X and Strassmann, JE and Queller, DC}, title = {Dictyostelium development shows a novel pattern of evolutionary conservation.}, journal = {Molecular biology and evolution}, volume = {30}, number = {4}, pages = {977-984}, doi = {10.1093/molbev/mst007}, pmid = {23329689}, issn = {1537-1719}, mesh = {Animals ; Biological Evolution ; Conserved Sequence ; Dictyostelium/*genetics/metabolism/physiology ; Gene Expression ; *Gene Expression Regulation, Developmental ; Genes, Protozoan ; Models, Genetic ; Sequence Analysis, RNA ; }, abstract = {von Baer's law states that early stages of animal development are the most conserved. More recent evidence supports a modified "hourglass" pattern in which an early but somewhat later stage is most conserved. Both patterns have been explained by the relative complexity of either temporal or spatial interactions; the greatest conservation and lowest evolvability occur at the time of the most complex interactions, because these cause larger effects that are harder for selection to alter. This general kind of explanation might apply universally across independent multicellular systems, as supported by the recent finding of the hourglass pattern in plants. We use RNA-seq expression data from the development of the slime mold Dictyostelium to demonstrate that it does not follow either of the two canonical patterns but instead tends to show the strongest conservation and weakest evolvability late in development. We propose that this is consistent with a version of the spatial constraints model, modified for organisms that never achieve a high degree of developmental modularity.}, } @article {pmid23327985, year = {2013}, author = {Donley, N and Thayer, MJ}, title = {DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability.}, journal = {Seminars in cancer biology}, volume = {23}, number = {2}, pages = {80-89}, pmid = {23327985}, issn = {1096-3650}, support = {R01 CA131967/CA/NCI NIH HHS/United States ; T32 GM071338/GM/NIGMS NIH HHS/United States ; CA104693/CA/NCI NIH HHS/United States ; CA131967/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; DNA Replication/*genetics ; DNA Replication Timing/genetics/*physiology ; Epigenesis, Genetic/physiology ; Gene Expression Regulation, Neoplastic ; Genomic Instability/*genetics ; Humans ; Models, Biological ; Neoplasms/*genetics ; Time Factors ; }, abstract = {Normal cellular division requires that the genome be faithfully replicated to ensure that unaltered genomic information is passed from one generation to the next. DNA replication initiates from thousands of origins scattered throughout the genome every cell cycle; however, not all origins initiate replication at the same time. A vast amount of work over the years indicates that different origins along each eukaryotic chromosome are activated in early, middle or late S phase. This temporal control of DNA replication is referred to as the replication-timing program. The replication-timing program represents a very stable epigenetic feature of chromosomes. Recent evidence has indicated that the replication-timing program can influence the spatial distribution of mutagenic events such that certain regions of the genome experience increased spontaneous mutagenesis compared to surrounding regions. This influence has helped shape the genomes of humans and other multicellular organisms and can affect the distribution of mutations in somatic cells. It is also becoming clear that the replication-timing program is deregulated in many disease states, including cancer. Aberrant DNA replication timing is associated with changes in gene expression, changes in epigenetic modifications and an increased frequency of structural rearrangements. Furthermore, certain replication timing changes can directly lead to overt genomic instability and may explain unique mutational signatures that are present in cells that have undergone the recently described processes of "chromothripsis" and "kataegis". In this review, we will discuss how the normal replication timing program, as well as how alterations to this program, can contribute to the evolution of the genomic landscape in normal and cancerous cells.}, } @article {pmid23319632, year = {2013}, author = {Schirrmeister, BE and de Vos, JM and Antonelli, A and Bagheri, HC}, title = {Evolution of multicellularity coincided with increased diversification of cyanobacteria and the Great Oxidation Event.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {5}, pages = {1791-1796}, pmid = {23319632}, issn = {1091-6490}, support = {311024/ERC_/European Research Council/International ; }, mesh = {Atmosphere ; Bayes Theorem ; Biodiversity ; *Biological Evolution ; Cyanobacteria/classification/genetics/*metabolism ; Genetic Variation ; Markov Chains ; Molecular Sequence Data ; Monte Carlo Method ; Oxidation-Reduction ; Oxygen/*metabolism ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Species Specificity ; Time Factors ; }, abstract = {Cyanobacteria are among the most diverse prokaryotic phyla, with morphotypes ranging from unicellular to multicellular filamentous forms, including those able to terminally (i.e., irreversibly) differentiate in form and function. It has been suggested that cyanobacteria raised oxygen levels in the atmosphere around 2.45-2.32 billion y ago during the Great Oxidation Event (GOE), hence dramatically changing life on the planet. However, little is known about the temporal evolution of cyanobacterial lineages, and possible interplay between the origin of multicellularity, diversification of cyanobacteria, and the rise of atmospheric oxygen. We estimated divergence times of extant cyanobacterial lineages under Bayesian relaxed clocks for a dataset of 16S rRNA sequences representing the entire known diversity of this phylum. We tested whether the evolution of multicellularity overlaps with the GOE, and whether multicellularity is associated with significant shifts in diversification rates in cyanobacteria. Our results indicate an origin of cyanobacteria before the rise of atmospheric oxygen. The evolution of multicellular forms coincides with the onset of the GOE and an increase in diversification rates. These results suggest that multicellularity could have played a key role in triggering cyanobacterial evolution around the GOE.}, } @article {pmid23319343, year = {2012}, author = {Hernández-Hernández, V and Niklas, KJ and Newman, SA and Benítez, M}, title = {Dynamical patterning modules in plant development and evolution.}, journal = {The International journal of developmental biology}, volume = {56}, number = {9}, pages = {661-674}, doi = {10.1387/ijdb.120027mb}, pmid = {23319343}, issn = {1696-3547}, mesh = {*Biological Evolution ; Epigenesis, Genetic ; Gene Expression Regulation, Plant ; Plant Development/*genetics ; Plants/*genetics ; }, abstract = {Broad comparative studies at the level of developmental processes are necessary to fully understand the evolution of development and phenotypes. The concept of dynamical patterning modules (DPMs) provides a framework for studying developmental processes in the context of wide comparative analyses. DPMs are defined as sets of ancient, conserved gene products and molecular networks, in conjunction with the physical morphogenetic and patterning processes they mobilize in the context of multicellularity. The theoretical framework based on DPMs originally postulated that each module generates a key morphological motif of the basic animal body plans and organ forms. Here, we use a previous definition of the plant multicellular body plan and describe the basic DPMs underlying the main features of plant development. For each DPM, we identify characteristic molecules and molecular networks, and when possible, the physical processes they mobilize. We then briefly review the phyletic distribution of these molecules across the various plant lineages. Although many of the basic plant DPMs are significantly different from those of animals, the framework established by a DPM perspective on plant development is essential for comparative analyses aiming to provide a truly mechanistic explanation for organic development across all plant and animal lineages.}, } @article {pmid23315654, year = {2013}, author = {Parfrey, LW and Lahr, DJ}, title = {Multicellularity arose several times in the evolution of eukaryotes (response to DOI 10.1002/bies.201100187).}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {4}, pages = {339-347}, doi = {10.1002/bies.201200143}, pmid = {23315654}, issn = {1521-1878}, mesh = {Animals ; *Cell Polarity ; Dictyostelium/*cytology ; Epithelial Cells/*physiology ; Humans ; }, abstract = {The cellular slime mold Dictyostelium has cell-cell connections similar in structure, function, and underlying molecular mechanisms to animal epithelial cells. These similarities form the basis for the proposal that multicellularity is ancestral to the clade containing animals, fungi, and Amoebozoa (including Dictyostelium): Amorphea (formerly "unikonts"). This hypothesis is intriguing and if true could precipitate a paradigm shift. However, phylogenetic analyses of two key genes reveal patterns inconsistent with a single origin of multicellularity. A single origin in Amorphea would also require loss of multicellularity in each of the many unicellular lineages within this clade. Further, there are numerous other origins of multicellularity within eukaryotes, including three within Amorphea, that are not characterized by these structural and mechanistic similarities. Instead, convergent evolution resulting from similar selective pressures for forming multicellular structures with motile and differentiated cells is the most likely explanation for the observed similarities between animal and dictyostelid cell-cell connections.}, } @article {pmid23313713, year = {2013}, author = {Völgyi, B and Kovács-Oller, T and Atlasz, T and Wilhelm, M and Gábriel, R}, title = {Gap junctional coupling in the vertebrate retina: variations on one theme?.}, journal = {Progress in retinal and eye research}, volume = {34}, number = {}, pages = {1-18}, doi = {10.1016/j.preteyeres.2012.12.002}, pmid = {23313713}, issn = {1873-1635}, mesh = {Animals ; Connexins/metabolism/physiology ; Electrical Synapses/physiology ; Gap Junctions/*physiology ; Retina/cytology/*physiology ; Vertebrates/*physiology ; }, abstract = {Gap junctions connect cells in the bodies of all multicellular organisms, forming either homologous or heterologous (i.e. established between identical or different cell types, respectively) cell-to-cell contacts by utilizing identical (homotypic) or different (heterotypic) connexin protein subunits. Gap junctions in the nervous system serve electrical signaling between neurons, thus they are also called electrical synapses. Such electrical synapses are particularly abundant in the vertebrate retina where they are specialized to form links between neurons as well as glial cells. In this article, we summarize recent findings on retinal cell-to-cell coupling in different vertebrates and identify general features in the light of the evergrowing body of data. In particular, we describe and discuss tracer coupling patterns, connexin proteins, junctional conductances and modulatory processes. This multispecies comparison serves to point out that most features are remarkably conserved across the vertebrate classes, including (i) the cell types connected via electrical synapses; (ii) the connexin makeup and the conductance of each cell-to-cell contact; (iii) the probable function of each gap junction in retinal circuitry; (iv) the fact that gap junctions underlie both electrical and/or tracer coupling between glial cells. These pan-vertebrate features thus demonstrate that retinal gap junctions have changed little during the over 500 million years of vertebrate evolution. Therefore, the fundamental architecture of electrically coupled retinal circuits seems as old as the retina itself, indicating that gap junctions deeply incorporated in retinal wiring from the very beginning of the eye formation of vertebrates. In addition to hard wiring provided by fast synaptic transmitter-releasing neurons and soft wiring contributed by peptidergic, aminergic and purinergic systems, electrical coupling may serve as the 'skeleton' of lateral processing, enabling important functions such as signal averaging and synchronization.}, } @article {pmid23313199, year = {2013}, author = {Okuyama, H and Yoshida, T and Endo, H and Nakayama, M and Nonomura, N and Nishimura, K and Inoue, M}, title = {Involvement of heregulin/HER3 in the primary culture of human urothelial cancer.}, journal = {The Journal of urology}, volume = {190}, number = {1}, pages = {302-310}, doi = {10.1016/j.juro.2012.12.106}, pmid = {23313199}, issn = {1527-3792}, mesh = {Blotting, Western ; Carcinoma, Transitional Cell/drug therapy/*pathology ; Cell Proliferation ; Humans ; Immunohistochemistry ; Molecular Targeted Therapy ; Neuregulin-1/*pharmacology ; Polymerase Chain Reaction/methods ; Receptor, ErbB-3/genetics/*metabolism ; Sensitivity and Specificity ; Signal Transduction ; Spheroids, Cellular/drug effects ; Transplantation, Heterologous ; Tumor Cells, Cultured/*drug effects ; Urinary Bladder Neoplasms/drug therapy/*pathology ; }, abstract = {PURPOSE: We previously established a novel method of human colorectal cancer primary culture. This method, termed the cancer tissue originated spheroid method, involves the preparation of multicellular spheroids of primary cancer cells that are cultured so that cell-cell contact is maintained. We applied this method to human urothelial cancer.

MATERIALS AND METHODS: Cancer tissue originated spheroids were prepared from xenografts or primary human bladder urothelial cancer tumors following the same protocol used for human colorectal cancer. Cancer tissue originated spheroids were characterized using immunohistochemistry, Western blot and polymerase chain reaction.

RESULTS: We established a xenograft from a primary bladder urothelial cancer, and isolated and cultured cancer tissue originated spheroids from the xenograft tumor. Cancer tissue originated spheroids retained the characteristics of the original tumor and those of the xenograft. Heregulin promoted cancer tissue originated spheroid growth, and inhibitors of PI3K and mTOR inhibited heregulin induced growth, as did lapatinib but not erlotinib. We also prepared cancer tissue originated spheroids from primary bladder urothelial cancer. The success rate of establishing primary cancer tissue originated spheroids from nonmuscle invasive urothelial cancer was 90.7% and that from muscle invasive cancer was 68.2%. The overall success rate was 84.2%. Heregulin promoted the growth of primary cancer tissue originated spheroids from 4 of 7 patients.

CONCLUSIONS: We report a method of establishing primary cultures of human urothelial cancer cells. Growth stimulation by heregulin in cancer tissue originated spheroids from xenografts and primary tumors suggests the possibility of molecular targeting therapy against HER3 signaling for human urothelial cancer. The cancer tissue originated spheroid method might be useful for selecting patients for molecular targeting drugs such as lapatinib.}, } @article {pmid23312067, year = {2013}, author = {Dawson, SC and Paredez, AR}, title = {Alternative cytoskeletal landscapes: cytoskeletal novelty and evolution in basal excavate protists.}, journal = {Current opinion in cell biology}, volume = {25}, number = {1}, pages = {134-141}, pmid = {23312067}, issn = {1879-0410}, support = {R01 AI077571/AI/NIAID NIH HHS/United States ; }, mesh = {Actins/metabolism ; Animals ; *Biological Evolution ; Cytoskeleton/*metabolism ; Eukaryota/*cytology/genetics/ultrastructure ; Genome/genetics ; Humans ; Microtubules/metabolism ; Phylogeny ; Proteins/metabolism ; Species Specificity ; }, abstract = {Microbial eukaryotes encompass the majority of eukaryotic evolutionary and cytoskeletal diversity. The cytoskeletal complexity observed in multicellular organisms appears to be an expansion of components present in genomes of diverse microbial eukaryotes such as the basal lineage of flagellates, the Excavata. Excavate protists have complex and diverse cytoskeletal architectures and life cycles-essentially alternative cytoskeletal 'landscapes'-yet still possess conserved microtubule-associated and actin-associated proteins. Comparative genomic analyses have revealed that a subset of excavates, however, lack many canonical actin-binding proteins central to actin cytoskeleton function in other eukaryotes. Overall, excavates possess numerous uncharacterized and 'hypothetical' genes, and may represent an undiscovered reservoir of novel cytoskeletal genes and cytoskeletal mechanisms. The continued development of molecular genetic tools in these complex microbial eukaryotes will undoubtedly contribute to our overall understanding of cytoskeletal diversity and evolution.}, } @article {pmid23305242, year = {2013}, author = {Benson, K and Cramer, S and Galla, HJ}, title = {Impedance-based cell monitoring: barrier properties and beyond.}, journal = {Fluids and barriers of the CNS}, volume = {10}, number = {1}, pages = {5}, pmid = {23305242}, issn = {2045-8118}, abstract = {In multicellular organisms epithelial and endothelial cells form selective permeable interfaces between tissue compartments of different chemical compositions. Tight junctions which connect adjacent cells, control the passage of molecules across the barrier and, in addition, facilitate active transport processes. The cellular barriers are not static but can be deliberately modulated by exposure to specific external stimuli. In vitro models representing the essential absorption barriers of the body are nowadays available, thus allowing investigation of the parameters that control permeability as well as transport processes across those barriers. Independent of the origin of the barrier forming cells, techniques are needed to quantify their barrier integrity. One simple assay is to measure the permeability for given hydrophilic substrates possessing different molecular weights like sucrose or dextrans. However, this technique is time-consuming and labor-intensive. Moreover, radioactive or fluorescently-labeled substrates are needed to allow easy analytical detection. Finally, if transport processes are investigated, the standard permeant may interfere with the transport process under investigation or might even alter the barrier integrity by itself. Thus, independent, non-invasive techniques are needed to quantify the barrier integrity continuously during the experiment. Such techniques are available and are mainly based on the measurement of the transendothelial or transepithelial electrical resistance (TEER) of barrier forming cells grown on porous membranes. Simple devices using two sets of electrodes (so-called Voltohmeters) are widely used. In addition, an easy-to-use physical technique called impedance spectroscopy allows the continuous analysis of both the TEER and the electrical capacitance giving additional information about the barrier properties of cells grown on permeable membranes. This technique is useful as a quality control for barrier forming cells. Another impedance-based approach requires cells to be grown directly on solid, micro-structured electrodes. Here, we will discuss the physical background of the different techniques; advantages, disadvantages, and applications will be scrutinized. The aim is to give the reader a comprehensive understanding concerning the range and limits of the application, mainly focusing on endothelial cells.}, } @article {pmid23300255, year = {2013}, author = {Smith, DR and Hamaji, T and Olson, BJ and Durand, PM and Ferris, P and Michod, RE and Featherston, J and Nozaki, H and Keeling, PJ}, title = {Organelle genome complexity scales positively with organism size in volvocine green algae.}, journal = {Molecular biology and evolution}, volume = {30}, number = {4}, pages = {793-797}, doi = {10.1093/molbev/mst002}, pmid = {23300255}, issn = {1537-1719}, mesh = {Chlamydomonas reinhardtii/cytology/*genetics ; Evolution, Molecular ; Genetic Drift ; Genetic Variation ; *Genome, Mitochondrial ; Genome, Plant ; *Genome, Plastid ; Mitochondria/*genetics ; Models, Genetic ; Plastids/*genetics ; Volvocida/cytology/genetics ; }, abstract = {It has been argued that for certain lineages, noncoding DNA expansion is a consequence of the increased random genetic drift associated with long-term escalations in organism size. But a lack of data has prevented the investigation of this hypothesis in most plastid-bearing protists. Here, using newly sequenced mitochondrial and plastid genomes, we explore the relationship between organelle DNA noncoding content and organism size within volvocine green algae. By looking at unicellular, colonial, and differentiated multicellular algae, we show that organelle DNA complexity scales positively with species size and cell number across the volvocine lineage. Moreover, silent-site genetic diversity data suggest that the volvocine species with the largest cell numbers and most bloated organelle genomes have the smallest effective population sizes. Together, these findings support the view that nonadaptive processes, like random genetic drift, promote the expansion of noncoding regions in organelle genomes.}, } @article {pmid23299670, year = {2013}, author = {Bogaert, KA and Arun, A and Coelho, SM and De Clerck, O}, title = {Brown algae as a model for plant organogenesis.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {959}, number = {}, pages = {97-125}, doi = {10.1007/978-1-62703-221-6_6}, pmid = {23299670}, issn = {1940-6029}, mesh = {Organogenesis/genetics/*physiology ; Phaeophyta/genetics/*physiology ; }, abstract = {Brown algae are an extremely interesting, but surprisingly poorly explored, group of organisms. They are one of only five eukaryotic lineages to have independently evolved complex multicellularity, which they express through a wide variety of morphologies ranging from uniseriate branched filaments to complex parenchymatous thalli with multiple cell types. Despite their very distinct evolutionary history, brown algae and land plants share a striking amount of developmental features. This has led to an interest in several aspects of brown algal development, including embryogenesis, polarity, cell cycle, asymmetric cell division and a putative role for plant hormone signalling. This review describes how investigations using brown algal models have helped to increase our understanding of the processes controlling early embryo development, in particular polarization, axis formation and asymmetric cell division. Additionally, the diversity of life cycles in the brown lineage and the emergence of Ectocarpus as a powerful model organism, are affording interesting insights on the molecular mechanisms underlying haploid-diploid life cycles. The use of these and other emerging brown algal models will undoubtedly add to our knowledge on the mechanisms that regulate development in multicellular photosynthetic organisms.}, } @article {pmid23291162, year = {2013}, author = {Duncan, O and van der Merwe, MJ and Daley, DO and Whelan, J}, title = {The outer mitochondrial membrane in higher plants.}, journal = {Trends in plant science}, volume = {18}, number = {4}, pages = {207-217}, doi = {10.1016/j.tplants.2012.12.004}, pmid = {23291162}, issn = {1878-4372}, mesh = {Arabidopsis/genetics/*metabolism/physiology ; Arabidopsis Proteins/genetics/metabolism ; Biological Evolution ; Lipids ; Membrane Proteins/genetics/*metabolism ; Mitochondria/*metabolism ; Mitochondrial Membranes/*metabolism ; Mitochondrial Proteins/genetics/metabolism ; Phylogeny ; Protein Transport ; Proteome ; Signal Transduction ; Stress, Physiological ; }, abstract = {The acquisition and integration of intracellular organelles, such as mitochondria and plastids, were important steps in the emergence of complex multicellular life. Although the outer membranes of these organelles have lost many of the functions of their free-living bacterial ancestor, others were acquired during organellogenesis. To date, the biological roles of these proteins have not been systematically characterized. In this review, we discuss the evolutionary origins and functions of outer membrane mitochondrial (OMM) proteins in Arabidopsis thaliana. Our analysis, using phylogenetic inference, indicates that several OMM proteins either acquired novel functional roles or were recruited from other subcellular localizations during evolution in Arabidopsis. These observations suggest the existence of novel communication routes and functions between organelles within plant cells.}, } @article {pmid23289572, year = {2013}, author = {Ross, L and Hardy, NB and Okusu, A and Normark, BB}, title = {Large population size predicts the distribution of asexuality in scale insects.}, journal = {Evolution; international journal of organic evolution}, volume = {67}, number = {1}, pages = {196-206}, doi = {10.1111/j.1558-5646.2012.01784.x}, pmid = {23289572}, issn = {1558-5646}, mesh = {Animals ; Evolution, Molecular ; Extinction, Biological ; Hemiptera/*genetics ; Models, Theoretical ; Parthenogenesis/*genetics ; Phylogeny ; Population/genetics ; }, abstract = {Understanding why some organisms reproduce by sexual reproduction while others can reproduce asexually remains an important unsolved problem in evolutionary biology. Simple demography suggests that asexuals should outcompete sexually reproducing organisms, because of their higher intrinsic rate of increase. However, the majority of multicellular organisms have sexual reproduction. The widely accepted explanation for this apparent contradiction is that asexual lineages have a higher extinction rate. A number of models have indicated that population size might play a crucial role in the evolution of asexuality. The strength of processes that lead to extinction of asexual species is reduced when population sizes get very large, so that the long-term advantage of sexual over asexual reproduction may become negligible. Here, we use a comparative approach using scale insects (Coccoidea, Hemiptera) to show that asexuality is indeed more common in species with larger population density and geographic distribution and we also show that asexual species tend to be more polyphagous. We discuss the implication of our findings for previously observed patterns of asexuality in agricultural pests.}, } @article {pmid23281188, year = {2013}, author = {Harrison, F}, title = {Bacterial cooperation in the wild and in the clinic: are pathogen social behaviours relevant outside the laboratory?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {2}, pages = {108-112}, pmid = {23281188}, issn = {1521-1878}, mesh = {Animals ; Bacteria/growth & development/*pathogenicity ; Bacterial Secretion Systems/*physiology ; Biological Evolution ; Host-Pathogen Interactions ; Humans ; Laboratories ; Microbial Consortia/*physiology ; Microbial Interactions/*physiology ; Selection, Genetic ; Virulence ; Virulence Factors/physiology ; }, abstract = {Individual bacterial cells can communicate via quorum sensing, cooperate to harvest nutrients from their environment, form multicellular biofilms, compete over resources and even kill one another. When the environment that bacteria inhabit is an animal host, these social behaviours mediate virulence. Over the last decade, much attention has focussed on the ecology, evolution and pathology of bacterial cooperation, and the possibility that it could be exploited or destabilised to treat infections. But how far can we really extrapolate from theoretical predictions and laboratory experiments to make inferences about 'cooperative' behaviours in hosts and reservoirs? To determine the likely importance and evolution of cooperation 'in the wild', several questions must be addressed. A recent paper that reports the dynamics of bacterial cooperation and virulence in a field experiment provides an excellent nucleus for bringing together key empirical and theoretical results which help us to frame - if not completely to answer - these questions.}, } @article {pmid23279048, year = {2013}, author = {Zhou, K and Zhang, WY and Pan, HM and Li, JH and Yue, HD and Xiao, T and Wu, LF}, title = {Adaptation of spherical multicellular magnetotactic prokaryotes to the geochemically variable habitat of an intertidal zone.}, journal = {Environmental microbiology}, volume = {15}, number = {5}, pages = {1595-1605}, doi = {10.1111/1462-2920.12057}, pmid = {23279048}, issn = {1462-2920}, mesh = {Adaptation, Physiological ; Deltaproteobacteria/classification/genetics/*physiology/ultrastructure ; *Ecosystem ; Geologic Sediments/*microbiology ; Magnetics ; Phylogeny ; Prokaryotic Cells/classification/physiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {A combination of microscopic, molecular and biogeochemical methods was used to study the structure, phylogenetics and vertical distribution of spherical multicellular magnetotactic prokaryotes (MMPs) of intertidal sediments in the Yellow Sea. These MMPs were 5.5 μm in diameter and composed of approximately 15-30 cells. They synthesized bullet-shaped magnetites in chains or clusters. Phylogenetic analysis of 16S rRNA gene sequences suggested that these MMPs represent a novel species affiliated to the Deltaproteobacteria. To study their vertical distribution and the relationship to geochemical parameters, sediment cores were collected after the redox potential was measured in situ. The sediments were composed of yellow, grey and black layers from the surface to depth. The spherical MMPs were concentrated near the grey-black layer transition at a depth of 8-12 cm, while coccoid-shaped magnetotactic bacteria near the yellow-grey layer transition at a depth of 3-5 cm. The intertidal MMPs showed a deeper distribution at more reduced environments than coccoid-shaped magnetotactic bacteria, and MMPs in lagoon sediments. Additionally the MMPs were concentrated significantly in layers with high proportion of fine sand and total organic carbon, rich in leachable iron but poor in nitrate. These results show an adaptation of spherical MMPs to the peculiar intertidal sediment habitat.}, } @article {pmid25525610, year = {2013}, author = {Chernet, B and Levin, M}, title = {Endogenous Voltage Potentials and the Microenvironment: Bioelectric Signals that Reveal, Induce and Normalize Cancer.}, journal = {Journal of clinical & experimental oncology}, volume = {Suppl 1}, number = {}, pages = {}, pmid = {25525610}, issn = {2324-9110}, support = {R01 AR055993/AR/NIAMS NIH HHS/United States ; R01 AR061988/AR/NIAMS NIH HHS/United States ; }, abstract = {Cancer may be a disease of geometry: a misregulation of the field of information that orchestrates individual cells' activities towards normal anatomy. Recent work identified molecular mechanisms underlying a novel system of developmental control: bioelectric gradients. Endogenous spatio-temporal differences in resting potential of non-neural cells provide instructive cues for cell regulation and complex patterning during embryogenesis and regeneration. It is now appreciated that these cues are an important layer of the dysregulation of cell: cell interactions that leads to cancer. Abnormal depolarization of resting potential (Vmem) is a convenient marker for neoplasia and activates a metastatic phenotype in genetically-normal cells in vivo. Moreover, oncogene expression depolarizes cells that form tumor-like structures, but is unable to form tumors if this depolarization is artificially prevented by misexpression of hyperpolarizing ion channels. Vmem triggers metastatic behaviors at considerable distance, mediated by transcriptional and epigenetic effects of electrically-modulated flows of serotonin and butyrate. While in vivo data on voltages in carcinogenesis comes mainly from the amphibian model, unbiased genetic screens and network profiling in rodents and human tissues reveal several ion channel proteins as bona fide oncogene and promising targets for cancer drug development. However, we propose that a focus on specific channel genes is just the tip of the iceberg. Bioelectric state is determined by post-translational gating of ion channels, not only from genetically-specified complements of ion translocators. A better model is a statistical dynamics view of spatial Vmem gradients. Cancer may not originate at the single cell level, since gap junctional coupling results in multi-cellular physiological networks with multiple stable attractors in bioelectrical state space. New medical applications await a detailed understanding of the mechanisms by which organ target morphology stored in real-time patterns of ion flows is perceived or mis-perceived by cells. Mastery of somatic voltage gradients will lead to cancer normalization or rebooting strategies, such as those that occur in regenerating and embryonic organs, resulting in transformative advances in basic biology and oncology.}, } @article {pmid24958261, year = {2013}, author = {Takemoto, K and Yoshitake, I}, title = {Limited influence of oxygen on the evolution of chemical diversity in metabolic networks.}, journal = {Metabolites}, volume = {3}, number = {4}, pages = {979-992}, pmid = {24958261}, issn = {2218-1989}, abstract = {Oxygen is thought to promote species and biomolecule diversity. Previous studies have suggested that oxygen expands metabolic networks by acquiring metabolites with different chemical properties (higher hydrophobicity, for example). However, such conclusions are typically based on biased evaluation, and are therefore non-conclusive. Thus, we re-investigated the effect of oxygen on metabolic evolution using a phylogenetic comparative method and metadata analysis to reduce the bias as much as possible. Notably, we found no difference in metabolic network expansion between aerobes and anaerobes when evaluating phylogenetic relationships. Furthermore, we showed that previous studies have overestimated or underestimated the degrees of differences in the chemical properties (e.g., hydrophobicity) between oxic and anoxic metabolites in metabolic networks of unicellular organisms; however, such overestimation was not observed when considering the metabolic networks of multicellular organisms. These findings indicate that the contribution of oxygen to increased chemical diversity in metabolic networks is lower than previously thought; rather, phylogenetic signals and cell-cell communication result in increased chemical diversity. However, this conclusion does not contradict the effect of oxygen on metabolic evolution; instead, it provides a deeper understanding of how oxygen contributes to metabolic evolution despite several limitations in data analysis methods.}, } @article {pmid24833059, year = {2013}, author = {Gramzow, L and Theißen, G}, title = {Phylogenomics of MADS-Box Genes in Plants - Two Opposing Life Styles in One Gene Family.}, journal = {Biology}, volume = {2}, number = {3}, pages = {1150-1164}, pmid = {24833059}, issn = {2079-7737}, abstract = {The development of multicellular eukaryotes, according to their body plan, is often directed by members of multigene families that encode transcription factors. MADS (for MINICHROMOSOME MAINTENANCE1, AGAMOUS, DEFICIENS and SERUM RESPONSE FACTOR)-box genes form one of those families controlling nearly all major aspects of plant development. Knowing the complete complement of MADS-box genes in sequenced plant genomes will allow a better understanding of the evolutionary patterns of these genes and the association of their evolution with the evolution of plant morphologies. Here, we have applied a combination of automatic and manual annotations to identify the complete set of MADS-box genes in 17 plant genomes. Furthermore, three plant genomes were reanalyzed and published datasets were used for four genomes such that more than 2,600 genes from 24 species were classified into the two types of MADS-box genes, Type I and Type II. Our results extend previous studies, highlighting the remarkably different evolutionary patterns of Type I and Type II genes and provide a basis for further studies on the evolution and function of MADS-box genes.}, } @article {pmid24769743, year = {2013}, author = {Torday, JS}, title = {Evolutionary biology redux.}, journal = {Perspectives in biology and medicine}, volume = {56}, number = {4}, pages = {455-484}, doi = {10.1353/pbm.2013.0038}, pmid = {24769743}, issn = {1529-8795}, mesh = {Aging ; Animals ; *Biological Evolution ; Cell Communication ; Gene Expression Regulation ; Homeostasis ; Humans ; Models, Biological ; Phylogeny ; Selection, Genetic ; Signal Transduction ; }, abstract = {This article offers a novel, enlightened concept for determining the mechanism of evolution. It is based on homeostasis, which distinguishes life from non-life and as such is the universal mechanism for the evolution of all living organisms. This view of evolution is logical, mechanistic, non-scalar, predictive, testable, and falsifiable, and it illuminates the epistemological relationships between physics and biology, ontogeny and phylogeny, development and aging, ultimate and proximate causation, health and disease. In addition to validating Haeckel's biogenetic law and Lamarckian epigenetics, reflecting the enabling value of the cellular approach, this perspective also expresses the evolutionary process at the cell-molecular level, since the mechanism of cell communication itself is universal in biology, in keeping with a Kuhnian paradigm shift. This approach may even elucidate the nature and evolution of consciousness as a manifestation of the cellular continuum from unicellular to multicellular life. We need such a functional genomic mechanism for the process of evolution if we are to make progress in biology and medicine. Like Copernican heliocentrism, a cellular approach to evolution may fundamentally change humankind's perceptions about our place in the universe.}, } @article {pmid23214131, year = {2012}, author = {Kikulska, A and Mlacki, M and Wilanowski, T}, title = {[The role of LSF/Grainyhead transcription factors in development and function of epidermal barrier in animals].}, journal = {Postepy biochemii}, volume = {58}, number = {1}, pages = {69-78}, pmid = {23214131}, issn = {0032-5422}, mesh = {Animals ; Apoptosis/genetics ; Cell Proliferation ; DNA-Binding Proteins/metabolism ; Disease Models, Animal ; Epidermis/embryology/*metabolism ; Gene Expression ; Humans ; Neoplasms/genetics ; Neural Tube Defects/genetics ; Transcription Factors/genetics/*metabolism ; Wound Healing/genetics ; }, abstract = {The LSF/Grainyhead family of transcription factors consists of proteins whose structure and functions have been preserved in the course of eukaryotic evolution--from primitive unicellular life forms to complex multicellular organisms. In the latter, these factors display tissue specificity and are active mainly in the covering epithelium. The roles of GRH factors are associated with regulation of expression of genes essential for correct differentiation and functioning of the epithelia of ectodermal origin. The Grh gene expression profiles are diverse and variable, especially during embryonic development. Research on the role of GRHL transcription factors is carried out on cellular and organismal level. In experimental animals, aberrant Grh gene expression leads to many diseases, including failure of epidermal wound healing and neural tube defects. Changes of these genes' expression levels are also linked to carcinogenesis. GRHL transcription factors participate in signaling pathways involved in cellular proliferation and apoptosis.}, } @article {pmid23211014, year = {2013}, author = {Sun, BF and Xiao, JH and He, SM and Liu, L and Murphy, RW and Huang, DW}, title = {Multiple ancient horizontal gene transfers and duplications in lepidopteran species.}, journal = {Insect molecular biology}, volume = {22}, number = {1}, pages = {72-87}, doi = {10.1111/imb.12004}, pmid = {23211014}, issn = {1365-2583}, mesh = {Animals ; Biological Evolution ; Bombyx/genetics ; Expressed Sequence Tags ; *Gene Transfer, Horizontal ; Genome, Insect ; Lepidoptera/*genetics/metabolism ; Phylogeny ; Selection, Genetic ; }, abstract = {Eukaryotic horizontal gene transfer (HGT) events are increasingly being discovered yet few reports have summarized multiple occurrences in a wide range of species. We systematically investigated HGT events in the order Lepidoptera by employing a series of filters. Bombyx mori, Danaus plexippus and Heliconius melpomene had 13, 12 and 12 HGTs, respectively, from bacteria and fungi. These HGTs contributed a total of 64 predicted genes: 22 to B. mori, 22 to D. plexippus and 20 to H. melpomene. Several new genes were generated by post-transfer duplications. Post-transfer duplication of a suite of functional HGTs has rarely been reported in higher organisms. The distributional patterns of paralogues for certain genes differed in the three species, indicating potential independent duplication or loss events. All of these HGTs had homologues expressed in some other lepidopterans, indicating ancient transfer events. Most HGTs were involved in the metabolism of sugar and amino acids. These HGTs appeared to have experienced amelioration, purifying selection and accelerated evolution to adapt to the background genome of the recipient. The discovery of ancient, massive HGTs and duplications in lepidopterans and their adaptive evolution provides further insights into the evolutionary significance of the events from donors to multicellular host recipients.}, } @article {pmid23209170, year = {2013}, author = {Chevin, LM and Gallet, R and Gomulkiewicz, R and Holt, RD and Fellous, S}, title = {Phenotypic plasticity in evolutionary rescue experiments.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {368}, number = {1610}, pages = {20120089}, pmid = {23209170}, issn = {1471-2970}, mesh = {*Adaptation, Physiological ; Animals ; Bacteria ; *Biological Evolution ; Competitive Behavior ; Environment ; Extinction, Biological ; Genetic Fitness/physiology ; Mutation ; *Phenotype ; Plants ; Population Density ; Population Dynamics ; Selection, Genetic ; Stress, Physiological ; }, abstract = {Population persistence in a new and stressful environment can be influenced by the plastic phenotypic responses of individuals to this environment, and by the genetic evolution of plasticity itself. This process has recently been investigated theoretically, but testing the quantitative predictions in the wild is challenging because (i) there are usually not enough population replicates to deal with the stochasticity of the evolutionary process, (ii) environmental conditions are not controlled, and (iii) measuring selection and the inheritance of traits affecting fitness is difficult in natural populations. As an alternative, predictions from theory can be tested in the laboratory with controlled experiments. To illustrate the feasibility of this approach, we briefly review the literature on the experimental evolution of plasticity, and on evolutionary rescue in the laboratory, paying particular attention to differences and similarities between microbes and multicellular eukaryotes. We then highlight a set of questions that could be addressed using this framework, which would enable testing the robustness of theoretical predictions, and provide new insights into areas that have received little theoretical attention to date.}, } @article {pmid23206384, year = {2013}, author = {Tarnita, CE and Taubes, CH and Nowak, MA}, title = {Evolutionary construction by staying together and coming together.}, journal = {Journal of theoretical biology}, volume = {320}, number = {}, pages = {10-22}, doi = {10.1016/j.jtbi.2012.11.022}, pmid = {23206384}, issn = {1095-8541}, support = {R01 GM078986/GM/NIGMS NIH HHS/United States ; R01GM078986/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Eukaryotic Cells/physiology ; *Models, Biological ; *Origin of Life ; }, abstract = {The evolutionary trajectory of life on earth is one of increasing size and complexity. Yet the standard equations of evolutionary dynamics describe mutation and selection among similar organisms that compete on the same level of organization. Here we begin to outline a mathematical theory that might help to explore how evolution can be constructive, how natural selection can lead from lower to higher levels of organization. We distinguish two fundamental operations, which we call 'staying together' and 'coming together'. Staying together means that individuals form larger units by not separating after reproduction, while coming together means that independent individuals form aggregates. Staying together can lead to specialization and division of labor, but the developmental program must evolve in the basic unit. Coming together can be creative by combining units with different properties. Both operations have been identified in the context of multicellularity, but they have been treated very similarly. Here we point out that staying together and coming together can be found at every level of biological construction and moreover that they face different evolutionary problems. The distinction is particularly clear in the context of cooperation and defection. For staying together the stability of cooperation takes the form of a developmental error threshold, while coming together leads to evolutionary games and requires a mechanism for the evolution of cooperation. We use our models to discuss simple aspects of the evolution of protocells, eukarya, multi-cellularity and animal societies.}, } @article {pmid23201916, year = {2013}, author = {Bailey, M and Christoforidou, Z and Lewis, M}, title = {Evolution of immune systems: specificity and autoreactivity.}, journal = {Autoimmunity reviews}, volume = {12}, number = {6}, pages = {643-647}, doi = {10.1016/j.autrev.2012.10.007}, pmid = {23201916}, issn = {1873-0183}, mesh = {Adaptive Immunity ; Animals ; *Biological Evolution ; Humans ; *Immune System ; }, abstract = {Multicellularity evolved well before 600 million years ago, and all multicellular animals have evolved since then with the need to protect against pathogens. There is no reason to expect their immune systems to be any less sophisticated than ours. The vertebrate system, based on rearranging immunoglobulin-superfamily domains, appears to have evolved partly as a result of chance insertion of RAG genes by horizontal transfer. Remarkably sophisticated systems for expansion of immunological repertoire have evolved in parallel in many groups of organisms. Vaccination of invertebrates against commercially important pathogens has been empirically successful, and suggests that the definition of an adaptive and innate immune system should no longer depend on the presence of memory and specificity, since these terms are hard to define in themselves. The evolution of randomly-created immunological repertoire also carries with it the potential for generating autoreactive specificities and consequent autoimmune damage. While invertebrates may use systems analogous to ours to control autoreactive specificities, they may have evolved alternative mechanisms which operate either at the level of individuals-within-populations rather than cells-within-individuals, by linking self-reactive specificities to regulatory pathways and non-self-reactive to effector pathways.}, } @article {pmid23194272, year = {2012}, author = {Armengaud, J and Christie-Oleza, JA and Clair, G and Malard, V and Duport, C}, title = {Exoproteomics: exploring the world around biological systems.}, journal = {Expert review of proteomics}, volume = {9}, number = {5}, pages = {561-575}, doi = {10.1586/epr.12.52}, pmid = {23194272}, issn = {1744-8387}, mesh = {Bacteria/isolation & purification/pathogenicity ; Cell Line ; Computational Biology ; *Extracellular Space/chemistry/metabolism ; High-Throughput Screening Assays/methods ; Humans ; Mass Spectrometry/methods ; *Peptides/chemistry/isolation & purification/metabolism ; *Proteins/classification/isolation & purification/metabolism ; Proteomics/*methods ; }, abstract = {The term 'exoproteome' describes the protein content that can be found in the extracellular proximity of a given biological system. These proteins arise from cellular secretion, other protein export mechanisms or cell lysis, but only the most stable proteins in this environment will remain in abundance. It has been shown that these proteins reflect the physiological state of the cells in a given condition and are indicators of how living systems interact with their environments. High-throughput proteomic approaches based on a shotgun strategy, and high-resolution mass spectrometers, have modified the authors' view of exoproteomes. In the present review, the authors describe how these new approaches should be exploited to obtain the maximum useful information from a sample, whatever its origin. The methodologies used for studying secretion from model cell lines derived from eukaryotic, multicellular organisms, virulence determinants of pathogens and environmental bacteria and their relationships with their habitats are illustrated with several examples. The implication of such data, in terms of proteogenomics and the discovery of novel protein functions, is discussed.}, } @article {pmid23188094, year = {2012}, author = {Gupta, GD and Kale, A and Kumar, V}, title = {Molecular evolution of translin superfamily proteins within the genomes of eubacteria, archaea and eukaryotes.}, journal = {Journal of molecular evolution}, volume = {75}, number = {5-6}, pages = {155-167}, pmid = {23188094}, issn = {1432-1432}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Archaea/genetics ; Carrier Proteins/chemistry/genetics/metabolism ; DNA-Binding Proteins/chemistry/*genetics/metabolism ; Eubacterium/genetics ; Eukaryota/genetics ; *Evolution, Molecular ; *Genome ; Humans ; Models, Molecular ; Molecular Sequence Data ; *Multigene Family ; Phylogeny ; Protein Conformation ; RNA-Binding Proteins/chemistry/*genetics/metabolism ; Sequence Alignment ; }, abstract = {Translin and its interacting partner protein, TRAX, are members of the translin superfamily. These proteins are involved in mRNA regulation and in promoting RISC activity by removing siRNA passenger strand cleavage products, and have been proposed to play roles in DNA repair and recombination. Both homomeric translin and heteromeric translin-TRAX complex bind to ssDNA and RNA; however, the heteromeric complex is a key activator in siRNA-mediated silencing in human and drosophila. The residues critical for RNase activity of the complex reside in TRAX sequence. Both translin and TRAX are well conserved in eukaryotes. In present work, a single translin superfamily protein is detected in Chloroflexi eubacteria, in the known phyla of archaea and in some unicellular eukaryotes. The prokaryotic proteins essentially share unique sequence motifs with eukaryotic TRAX, while the proteins possessing both the unique sequences and conserved indels of TRAX or translin can be identified from protists. Intriguingly, TRAX protein in all the known genomes of extant Chloroflexi share high sequence similarity and conserved indels with the archaeal protein, suggesting occurrence of TRAX at least at the time of Chloroflexi divergence as well as evolutionary relationship between Chloroflexi and archaea. The mirror phylogeny in phylogenetic tree, constructed using diverse translin and TRAX sequences, indicates gene duplication event leading to evolution of translin in unicellular eukaryotes, prior to divergence of multicellular eukayrotes. Since Chloroflexi has been debated to be near the last universal common ancestor, the present analysis indicates that TRAX may be useful to understand the tree of life.}, } @article {pmid23185420, year = {2012}, author = {Turnbull, C and Wilson, PD and Hoggard, S and Gillings, M and Palmer, C and Smith, S and Beattie, D and Hussey, S and Stow, A and Beattie, A}, title = {Primordial enemies: fungal pathogens in thrips societies.}, journal = {PloS one}, volume = {7}, number = {11}, pages = {e49737}, pmid = {23185420}, issn = {1932-6203}, mesh = {Animals ; Antifungal Agents/metabolism ; Behavior, Animal ; Biological Evolution ; Cordyceps/*pathogenicity/physiology ; Female ; Fungi/*pathogenicity/physiology ; Insecta ; Linear Models ; Male ; Thysanoptera/*microbiology ; }, abstract = {Microbial pathogens are ancient selective agents that have driven many aspects of multicellular evolution, including genetic, behavioural, chemical and immune defence systems. It appears that fungi specialised to attack insects were already present in the environments in which social insects first evolved and we hypothesise that if the early stages of social evolution required antifungal defences, then covariance between levels of sociality and antifungal defences might be evident in extant lineages, the defences becoming stronger with group size and increasing social organisation. Thus, we compared the activity of cuticular antifungal compounds in thrips species (Insecta: Thysanoptera) representing a gradient of increasing group size and sociality: solitary, communal, social and eusocial, against the entomopathogen Cordyceps bassiana. Solitary and communal species showed little or no activity. In contrast, the social and eusocial species killed this fungus, suggesting that the evolution of sociality has been accompanied by sharp increases in the effectiveness of antifungal compounds. The antiquity of fungal entomopathogens, demonstrated by fossil finds, coupled with the unequivocal response of thrips colonies to them shown here, suggests two new insights into the evolution of thrips sociality: First, traits that enabled nascent colonies to defend themselves against microbial pathogens should be added to those considered essential for social evolution. Second, limits to the strength of antimicrobials, through resource constraints or self-antibiosis, may have been overcome by increase in the numbers of individuals secreting them, thus driving increases in colony size. If this is the case for social thrips, then we may ask: did antimicrobial traits and microbes such as fungal entomopathogens play an integral part in the evolution of insect sociality in general?}, } @article {pmid23180579, year = {2013}, author = {Mukherjee, K and Campos, H and Kolaczkowski, B}, title = {Evolution of animal and plant dicers: early parallel duplications and recurrent adaptation of antiviral RNA binding in plants.}, journal = {Molecular biology and evolution}, volume = {30}, number = {3}, pages = {627-641}, pmid = {23180579}, issn = {1537-1719}, mesh = {Adaptation, Biological/genetics ; Amino Acid Sequence ; Animals ; Bayes Theorem ; Catalytic Domain ; Conserved Sequence ; *Evolution, Molecular ; Gene Duplication ; Likelihood Functions ; Models, Genetic ; Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Plant Proteins/chemistry/*genetics ; Plants/enzymology/genetics ; Protein Binding ; RNA Interference ; Ribonuclease III/chemistry/*genetics ; Selection, Genetic ; Sequence Analysis, Protein ; Surface Properties ; }, abstract = {RNA interference (RNAi) is a eukaryotic molecular system that serves two primary functions: 1) gene regulation and 2) protection against selfish elements such as viruses and transposable DNA. Although the biochemistry of RNAi has been detailed in model organisms, very little is known about the broad-scale patterns and forces that have shaped RNAi evolution. Here, we provide a comprehensive evolutionary analysis of the Dicer protein family, which carries out the initial RNA recognition and processing steps in the RNAi pathway. We show that Dicer genes duplicated and diversified independently in early animal and plant evolution, coincident with the origins of multicellularity. We identify a strong signature of long-term protein-coding adaptation that has continually reshaped the RNA-binding pocket of the plant Dicer responsible for antiviral immunity, suggesting an evolutionary arms race with viral factors. We also identify key changes in Dicer domain architecture and sequence leading to specialization in either gene-regulatory or protective functions in animal and plant paralogs. As a whole, these results reveal a dynamic picture in which the evolution of Dicer function has driven elaboration of parallel RNAi functional pathways in animals and plants.}, } @article {pmid23179353, year = {2012}, author = {Tang, YH and Han, SP and Kassahn, KS and Skarshewski, A and Rothnagel, JA and Smith, R}, title = {Complex evolutionary relationships among four classes of modular RNA-binding splicing regulators in eukaryotes: the hnRNP, SR, ELAV-like and CELF proteins.}, journal = {Journal of molecular evolution}, volume = {75}, number = {5-6}, pages = {214-228}, pmid = {23179353}, issn = {1432-1432}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; CCAAT-Enhancer-Binding Protein-delta/chemistry/genetics ; Cluster Analysis ; Computational Biology ; Consensus Sequence ; ELAV Proteins/chemistry/genetics ; Eukaryota/*genetics ; *Evolution, Molecular ; Heterogeneous-Nuclear Ribonucleoproteins/genetics ; Humans ; Molecular Sequence Data ; Nuclear Proteins/genetics ; Phylogeny ; *RNA Splicing ; RNA-Binding Proteins/*genetics ; Sequence Alignment ; Serine-Arginine Splicing Factors ; }, abstract = {Alternative RNA splicing in multicellular organisms is regulated by a large group of proteins of mainly unknown origin. To predict the functions of these proteins, classification of their domains at the sequence and structural level is necessary. We have focused on four groups of splicing regulators, the heterogeneous nuclear ribonucleoprotein (hnRNP), serine-arginine (SR), embryonic lethal, abnormal vision (ELAV)-like, and CUG-BP and ETR-like factor (CELF) proteins, that show increasing diversity among metazoa. Sequence and phylogenetic analyses were used to obtain a broader understanding of their evolutionary relationships. Surprisingly, when we characterised sequence similarities across full-length sequences and conserved domains of ten metazoan species, we found some hnRNPs were more closely related to SR, ELAV-like and CELF proteins than to other hnRNPs. Phylogenetic analyses and the distribution of the RRM domains suggest that these proteins diversified before the last common ancestor of the metazoans studied here through domain acquisition and duplication to create genes of mixed evolutionary origin. We propose that these proteins were derived independently rather than through the expansion of a single protein family. Our results highlight inconsistencies in the current classification system for these regulators, which does not adequately reflect their evolutionary relationships, and suggests that a domain-based classification scheme may have more utility.}, } @article {pmid23165352, year = {2013}, author = {Jolliffe, AK and Derry, WB}, title = {The TP53 signaling network in mammals and worms.}, journal = {Briefings in functional genomics}, volume = {12}, number = {2}, pages = {129-141}, doi = {10.1093/bfgp/els047}, pmid = {23165352}, issn = {2041-2657}, support = {MOP 79495//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Caenorhabditis elegans/*metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; Evolution, Molecular ; Humans ; Mammals/*metabolism ; *Signal Transduction ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {The nematode worm Caenorhabditis elegans has been an invaluable model organism for studying the molecular mechanisms that govern cell fate, from fundamental aspects of multicellular development to programmed cell death (apoptosis). The transparency of this organism permits visualization of cells in living animals at high resolution. The powerful genetics and functional genomics tools available in C. elegans allow for detailed analysis of gene function, including genes that are frequently deregulated in human diseases such as cancer. The TP53 protein is a critical suppressor of tumor formation in vertebrates, and the TP53 gene is mutated in over 50% of human cancers. TP53 suppresses malignancy by integrating a variety of cellular stresses that direct it to activate transcription of genes that help to repair the damage or trigger apoptotic death if the damage is beyond repair. The TP53 paralogs, TP63 and TP73, have distinct roles in development as well as overlapping functions with TP53 in apoptosis and repair, which complicates their analysis in vertebrates. C. elegans contains a single TP53 family member, cep-1, that shares properties of all three vertebrate genes and thus offers a simple system in which to study the biological functions of this important gene family. This review summarizes major advances in our understanding of the TP53 family using C. elegans as a model organism.}, } @article {pmid23163752, year = {2013}, author = {Belaidi, AA and Schwarz, G}, title = {Metal insertion into the molybdenum cofactor: product-substrate channelling demonstrates the functional origin of domain fusion in gephyrin.}, journal = {The Biochemical journal}, volume = {450}, number = {1}, pages = {149-157}, doi = {10.1042/BJ20121078}, pmid = {23163752}, issn = {1470-8728}, mesh = {Alternative Splicing ; Apoproteins/chemistry/genetics/metabolism ; Carrier Proteins/*chemistry/genetics/metabolism ; Coenzymes/*chemistry/metabolism ; Membrane Proteins/*chemistry/genetics/metabolism ; Metalloproteins/*chemistry/metabolism ; Molybdenum/*chemistry/metabolism ; Molybdenum Cofactors ; Protein Processing, Post-Translational ; Protein Structure, Tertiary ; Pteridines/*chemistry/metabolism ; Recombinant Proteins/chemistry/genetics/metabolism ; }, abstract = {The complexity of eukaryotic multicellular organisms relies on evolutionary developments that include compartmentalization, alternative splicing, protein domain fusion and post-translational modification. Mammalian gephyrin uniquely exemplifies these processes by combining two enzymatic functions within the biosynthesis of the Moco (molybdenum cofactor) in a multidomain protein. It also undergoes extensive alternative splicing, especially in neurons, where it also functions as a scaffold protein at inhibitory synapses. Two out of three gephyrin domains are homologous to bacterial Moco-synthetic proteins (G and E domain) while being fused by a third gephyrin-specific central C domain. In the present paper, we have established the in vitro Moco synthesis using purified components and demonstrated an over 300-fold increase in Moco synthesis for gephyrin compared with the isolated G domain, which synthesizes adenylylated molybdopterin, and E domain, which catalyses the metal insertion at physiological molybdate concentrations in an ATP-dependent manner. We show that the C domain impacts the catalytic efficacy of gephyrin, suggesting an important structural role in product-substrate channelling as depicted by a structural model that is in line with a face-to-face orientation of both active sites. Our functional studies demonstrate the evolutionary advantage of domain fusion in metabolic proteins, which can lead to the development of novel functions in higher eukaryotes.}, } @article {pmid23139082, year = {2013}, author = {Koonin, EV and Csuros, M and Rogozin, IB}, title = {Whence genes in pieces: reconstruction of the exon-intron gene structures of the last eukaryotic common ancestor and other ancestral eukaryotes.}, journal = {Wiley interdisciplinary reviews. RNA}, volume = {4}, number = {1}, pages = {93-105}, doi = {10.1002/wrna.1143}, pmid = {23139082}, issn = {1757-7012}, mesh = {Alternative Splicing ; Animals ; Biological Evolution ; Conserved Sequence/genetics ; Eukaryota/*genetics ; Evolution, Molecular ; Exons/*genetics ; Genome ; Humans ; Introns/*genetics ; Spliceosomes/genetics ; }, abstract = {In eukaryotes, protein-coding sequences are interrupted by non-coding sequences known as introns. During mRNA maturation, introns are excised by the spliceosome and the coding regions, exons, are spliced to form the mature coding region. The intron densities widely differ between eukaryotic lineages, from 6 to 7 introns per kb of coding sequence in vertebrates, some invertebrates and green plants, to only a few introns across the entire genome in many unicellular eukaryotes. Evolutionary reconstructions using maximum likelihood methods suggest intron-rich ancestors for each major group of eukaryotes. For the last common ancestor of animals, the highest intron density of all extant and extinct eukaryotes was inferred, at 120-130% of the human intron density. Furthermore, an intron density within 53-74% of the human values was inferred for the last eukaryotic common ancestor. Accordingly, evolution of eukaryotic genes in all lines of descent involved primarily intron loss, with substantial gain only at the bases of several branches including plants and animals. These conclusions have substantial biological implications indicating that the common ancestor of all modern eukaryotes was a complex organism with a gene architecture resembling those in multicellular organisms. Alternative splicing most likely initially appeared as an inevitable result of splicing errors and only later was employed to generate structural and functional diversification of proteins.}, } @article {pmid23136763, year = {2012}, author = {Kotolupov, VA and Isaeva, VV}, title = {[Cells in the system of multicelular organisms from positions of non-linear dynamics].}, journal = {Zhurnal evoliutsionnoi biokhimii i fiziologii}, volume = {48}, number = {5}, pages = {517-526}, pmid = {23136763}, issn = {0044-4529}, mesh = {Adaptation, Biological/*physiology ; Animals ; Apoptosis/*physiology ; Cell Differentiation/*physiology ; Homeostasis/*physiology ; *Models, Biological ; *Nonlinear Dynamics ; }, abstract = {The organism physiological systems forming a hierarchic network with mutual dependence and subordination can be considered as systems with non-linear dynamics including positive and negative feedbacks. In the course of evolution there occurred selection of robust, flexible, modular systems capable for adaptive self-organization by non-linear interaction of components, which leads to formation of the ordered in space and time robust and plastic organization of the whole. Cells of multicellular organisms are capable for coordinated "social" behavior with formation of ordered cell assemblies, which provides a possibility of morphological and functional variability correlating with manifestations of the large spectrum of adaptive reactions. The multicellular organism is the multilevel system with hierarchy of numerous subsystems capable for adaptive self-organization; disturbance of their homeostasis can lead to pathological changes. The healthy organism regulates homeostasis, self-renewal, differentiation, and apoptosis of cells serving its parts and construction blocks by preserving its integrity and controlling behavior of cells. The systemic approach taking into account biological regularities of the appearance and development of functions in evolution of multicellular organisms opens new possibilities for diagnostics and treatment of many diseases.}, } @article {pmid23134060, year = {2013}, author = {Glöckner, G and Noegel, AA}, title = {Comparative genomics in the Amoebozoa clade.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {88}, number = {1}, pages = {215-225}, doi = {10.1111/j.1469-185X.2012.00248.x}, pmid = {23134060}, issn = {1469-185X}, mesh = {Amoebozoa/*genetics ; Animals ; *Biological Evolution ; *Genome ; *Genomics ; Phylogeny ; }, abstract = {Amoeboid life forms can be found throughout the evolutionary tree. The greatest proportion of these life forms is found in the Amoebozoa clade, one of the six major eukaryote evolutionary branches. Despite its common origin this clade exhibits a wide diversity of lifestyles including free-living and parasitic species and species with multicellular and multinucleate life stages. In this group, development, cooperation, and social behaviour can be studied in addition to traits common to unicellular organisms. To date, only a few Amoebozoa genomes have been sequenced completely, however a number of expressed sequence tags (ESTs) and complete and draft genomes have become available recently for several species that represent some of the major evolutionary lineages in this clade. This resource allows us to compare and analyse the evolutionary history and fate of branch-specific genes if properly exploited. Despite the large evolutionary time scale since the emergence of the major groups the genomic organization in Amoebozoa has retained common features. The number of Amoebozoa-specific genetic inventions seems to be rather small. The emergence of subgroups is accompanied by gene and domain losses and acquisitions of bacterial gene material. The sophisticated developmental cycles of Myxogastria and Dictyosteliida likely have a common origin and are deeply rooted in amoebozoan evolution. In this review we describe initial approaches to comparative genomics in Amoebozoa, summarize recent findings, and identify goals for further studies.}, } @article {pmid23133603, year = {2012}, author = {Jami, SK and Clark, GB and Ayele, BT and Ashe, P and Kirti, PB}, title = {Genome-wide comparative analysis of annexin superfamily in plants.}, journal = {PloS one}, volume = {7}, number = {11}, pages = {e47801}, pmid = {23133603}, issn = {1932-6203}, mesh = {Amino Acid Motifs ; Annexins/genetics/*metabolism ; Arabidopsis/genetics ; Bayes Theorem ; Binding Sites ; Calcium/chemistry ; Chromosomes/ultrastructure ; Databases, Genetic ; Exons ; *Genome-Wide Association Study ; Introns ; Likelihood Functions ; Multigene Family ; Oryza/genetics ; Phylogeny ; Plants/*genetics ; Protein Structure, Tertiary ; }, abstract = {Most annexins are calcium-dependent, phospholipid-binding proteins with suggested functions in response to environmental stresses and signaling during plant growth and development. They have previously been identified and characterized in Arabidopsis and rice, and constitute a multigene family in plants. In this study, we performed a comparative analysis of annexin gene families in the sequenced genomes of Viridiplantae ranging from unicellular green algae to multicellular plants, and identified 149 genes. Phylogenetic studies of these deduced annexins classified them into nine different arbitrary groups. The occurrence and distribution of bona fide type II calcium binding sites within the four annexin domains were found to be different in each of these groups. Analysis of chromosomal distribution of annexin genes in rice, Arabidopsis and poplar revealed their localization on various chromosomes with some members also found on duplicated chromosomal segments leading to gene family expansion. Analysis of gene structure suggests sequential or differential loss of introns during the evolution of land plant annexin genes. Intron positions and phases are well conserved in annexin genes from representative genomes ranging from Physcomitrella to higher plants. The occurrence of alternative motifs such as K/R/HGD was found to be overlapping or at the mutated regions of the type II calcium binding sites indicating potential functional divergence in certain plant annexins. This study provides a basis for further functional analysis and characterization of annexin multigene families in the plant lineage.}, } @article {pmid23129619, year = {2012}, author = {Sung, W and Tucker, AE and Doak, TG and Choi, E and Thomas, WK and Lynch, M}, title = {Extraordinary genome stability in the ciliate Paramecium tetraurelia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {47}, pages = {19339-19344}, pmid = {23129619}, issn = {1091-6490}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Substitution/genetics ; DNA-Directed DNA Polymerase/metabolism ; Genome, Protozoan/*genetics ; Genomic Instability/*genetics ; Mitochondria/genetics ; Mutation Rate ; Paramecium tetraurelia/enzymology/*genetics ; Reproduction/genetics ; }, abstract = {Mutation plays a central role in all evolutionary processes and is also the basis of genetic disorders. Established base-substitution mutation rates in eukaryotes range between ∼5 × 10(-10) and 5 × 10(-8) per site per generation, but here we report a genome-wide estimate for Paramecium tetraurelia that is more than an order of magnitude lower than any previous eukaryotic estimate. Nevertheless, when the mutation rate per cell division is extrapolated to the length of the sexual cycle for this protist, the measure obtained is comparable to that for multicellular species with similar genome sizes. Because Paramecium has a transcriptionally silent germ-line nucleus, these results are consistent with the hypothesis that natural selection operates on the cumulative germ-line replication fidelity per episode of somatic gene expression, with the germ-line mutation rate per cell division evolving downward to the lower barrier imposed by random genetic drift. We observe ciliate-specific modifications of widely conserved amino acid sites in DNA polymerases as one potential explanation for unusually high levels of replication fidelity.}, } @article {pmid23128987, year = {2013}, author = {Bloemendal, S and Kück, U}, title = {Cell-to-cell communication in plants, animals, and fungi: a comparative review.}, journal = {Die Naturwissenschaften}, volume = {100}, number = {1}, pages = {3-19}, pmid = {23128987}, issn = {1432-1904}, mesh = {Animals ; Cell Communication/*physiology ; Fungi/*physiology ; *Plant Physiological Phenomena ; Plants/virology ; }, abstract = {Cell-to-cell communication is a prerequisite for differentiation and development in multicellular organisms. This communication has to be tightly regulated to ensure that cellular components such as organelles, macromolecules, hormones, or viruses leave the cell in a precisely organized way. During evolution, plants, animals, and fungi have developed similar ways of responding to this biological challenge. For example, in higher plants, plasmodesmata connect adjacent cells and allow communication to regulate differentiation and development. In animals, two main general structures that enable short- and long-range intercellular communication are known, namely gap junctions and tunneling nanotubes, respectively. Finally, filamentous fungi have also developed specialized structures called septal pores that allow intercellular communication via cytoplasmic flow. This review summarizes the underlying mechanisms for intercellular communication in these three eukaryotic groups and discusses its consequences for the regulation of differentiation and developmental processes.}, } @article {pmid23109712, year = {2013}, author = {Gest, N and Gautier, H and Stevens, R}, title = {Ascorbate as seen through plant evolution: the rise of a successful molecule?.}, journal = {Journal of experimental botany}, volume = {64}, number = {1}, pages = {33-53}, doi = {10.1093/jxb/ers297}, pmid = {23109712}, issn = {1460-2431}, mesh = {Antioxidants/metabolism ; Ascorbic Acid/*metabolism ; *Biological Evolution ; Biological Transport ; Origin of Life ; Plants/*metabolism ; }, abstract = {Ascorbate is a widespread and efficient antioxidant that has multiple functions in plants, traditionally associated with the reactions of photosynthesis. This review aims to look at ascorbate from an evolutionary perspective. Cyanobacteria, algae, and bryophytes contain lower concentrations of ascorbate than higher plants, where the molecule accumulates in high concentrations in both photosynthetic and non-photosynthetic organs and tissues. This increase in ascorbate concentration is paralleled by an increase in the number of isoforms of ascorbate peroxidase and the ascorbate regenerating enzymes mono- and dehydroascorbate reductase. One way of understanding the rise in ascorbate concentrations is to consider ascorbate as a molecule among others that has been subject to selection pressures during evolution, due to its cost or benefit for the cell and the organism. Ascorbate has a low cost in terms of synthesis and toxicity, and its benefits include protection of the glutathione pool and proper functioning of a range of enzymes. The hypothesis presented here is that these features would have favoured increasing roles for the molecule in the development and growth of multicellular organisms. This review then focuses on this diversity of roles for ascorbate in both photosynthetic and non-photosynthetic tissues of higher plants, including fruits and seeds, as well as further functions the molecule may possess by looking at other species. The review also highlights one of the trade-offs of domestication, which has often reduced or diluted ascorbate content in the quest for increased fruit growth and yield, with unknown consequences for the corresponding functional diversity, particularly in terms of stress resistance and adaptive responses to the environment.}, } @article {pmid23109363, year = {2013}, author = {Ríos-Barrera, LD and Riesgo-Escovar, JR}, title = {Regulating cell morphogenesis: the Drosophila Jun N-terminal kinase pathway.}, journal = {Genesis (New York, N.Y. : 2000)}, volume = {51}, number = {3}, pages = {147-162}, doi = {10.1002/dvg.22354}, pmid = {23109363}, issn = {1526-968X}, mesh = {Animals ; Drosophila/*enzymology/genetics/growth & development ; Gene Expression Regulation, Developmental ; JNK Mitogen-Activated Protein Kinases/genetics/*metabolism ; *MAP Kinase Signaling System ; Morphogenesis/*genetics ; }, abstract = {The Jun-N-terminal Kinase pathway (JNK), known also as stress activated protein kinase pathway (SAPK), is an eukaryotic evolutionarily conserved signaling pathway. From a purported evolutionarily "ancient" function as stress mediator, it evolved in multicellular eukaryotes to permanent roles in development, without leaving its original function. In Drosophila melanogaster, it is required for follicle cell morphogenesis, embryonic dorsal closure, pupal thoracic closure and genital disc rotation closure, all processes with requisite cell shape changes. Besides, it is activated during wound healing and in response to stress (UV irradiation, oxidative stress) where it may signal cell death or proliferation. Despite these varied roles, it has a conserved core of molecules that follow the MAPKKK/MAPKK/MAPK logic of mitogen activated protein kinases pathways. Regulation of the JNK pathway appears majorly negative, with phosphatases, transcription factors and proteins of novel structure "holding back" on JNK activation in different tissues. This particular mode of regulation may hark back to the pathway's origin as stress detector and responder, implying readiness to respond, from which the developmental roles may have evolved as conditions demanding obligate and predicted stress responses (i.e., embryonic dorsal closure viewed as a "wound of development").}, } @article {pmid23108939, year = {2012}, author = {Baluška, F}, title = {Rethinking origins of multicellularity: convergent evolution of epithelia in plants.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {34}, number = {12}, pages = {1085}, doi = {10.1002/bies.201200134}, pmid = {23108939}, issn = {1521-1878}, mesh = {Animals ; *Cell Polarity ; Dictyostelium/*cytology ; Epithelial Cells/*physiology ; Humans ; }, } @article {pmid23103169, year = {2012}, author = {Qian, W and Ma, D and Xiao, C and Wang, Z and Zhang, J}, title = {The genomic landscape and evolutionary resolution of antagonistic pleiotropy in yeast.}, journal = {Cell reports}, volume = {2}, number = {5}, pages = {1399-1410}, pmid = {23103169}, issn = {2211-1247}, support = {R01 GM067030/GM/NIGMS NIH HHS/United States ; R01 GM103232/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; *Biological Evolution ; Gene Deletion ; Gene Expression Regulation, Fungal ; Genetic Pleiotropy/*genetics ; Genetics, Population ; *Genome ; *Models, Genetic ; Saccharomyces cerevisiae/*genetics ; }, abstract = {Antagonistic pleiotropy (AP), or genetic tradeoff, is an important concept that is frequently invoked in theories of aging, cancer, genetic disease, and other common phenomena. However, the prevalence of AP, which genes are subject to AP, and to what extent and how AP may be resolved remain unclear. By measuring the fitness difference between the wild-type and null alleles of ~5,000 nonessential genes in yeast, we found that in any given environment, yeast expresses hundreds of genes that harm rather than benefit the organism, demonstrating widespread AP. Nonetheless, under sufficient selection, AP is often resolvable through regulatory evolution, primarily by trans-acting changes, although in one case we also detected a cis-acting change and localized its causal mutation. However, AP is resolved more slowly in smaller populations, predicting more unresolved AP in multicellular organisms than in yeast. These findings provide an empirical foundation for AP-dependent theories and have broad biomedical and evolutionary implications.}, } @article {pmid23093189, year = {2012}, author = {Yue, J and Hu, X and Sun, H and Yang, Y and Huang, J}, title = {Widespread impact of horizontal gene transfer on plant colonization of land.}, journal = {Nature communications}, volume = {3}, number = {}, pages = {1152}, pmid = {23093189}, issn = {2041-1723}, mesh = {Biological Evolution ; Bryopsida/genetics/physiology ; Gene Transfer, Horizontal/*genetics/physiology ; Genes, Plant/genetics/physiology ; Multigene Family/genetics/physiology ; Phylogeny ; Plant Development/genetics/physiology ; Plant Physiological Phenomena/genetics ; Plants/*genetics ; Sequence Alignment ; }, abstract = {In complex multicellular eukaryotes such as animals and plants, horizontal gene transfer is commonly considered rare with very limited evolutionary significance. Here we show that horizontal gene transfer is a dynamic process occurring frequently in the early evolution of land plants. Our genome analyses of the moss Physcomitrella patens identified 57 families of nuclear genes that were acquired from prokaryotes, fungi or viruses. Many of these gene families were transferred to the ancestors of green or land plants. Available experimental evidence shows that these anciently acquired genes are involved in some essential or plant-specific activities such as xylem formation, plant defence, nitrogen recycling as well as the biosynthesis of starch, polyamines, hormones and glutathione. These findings suggest that horizontal gene transfer had a critical role in the transition of plants from aquatic to terrestrial environments. On the basis of these findings, we propose a model of horizontal gene transfer mechanism in nonvascular and seedless vascular plants.}, } @article {pmid23084775, year = {2012}, author = {Guerriero, G}, title = {Putative chitin synthases from Branchiostoma floridae show extracellular matrix-related domains and mosaic structures.}, journal = {Genomics, proteomics & bioinformatics}, volume = {10}, number = {4}, pages = {197-207}, pmid = {23084775}, issn = {2210-3244}, support = {M 1315/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Amino Acid Sequence ; Animals ; Biological Evolution ; Chitin/chemistry/metabolism ; Chitin Synthase/*chemistry/*genetics/metabolism ; Chordata, Nonvertebrate/*enzymology/*genetics ; Computational Biology ; Discoidins ; Extracellular Matrix/chemistry/*metabolism ; Glycosyltransferases/chemistry/metabolism ; Lectins ; Models, Molecular ; Molecular Sequence Data ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; Protozoan Proteins ; }, abstract = {The transition from unicellular to multicellular life forms requires the development of a specialized structural component, the extracellular matrix (ECM). In Metazoans, there are two main supportive systems, which are based on chitin and collagen/hyaluronan, respectively. Chitin is the major constituent of fungal cell walls and arthropod exoskeleton. However, presence of chitin/chitooligosaccharides has been reported in lower chordates and during specific stages of vertebrate development. In this study, the occurrence of chitin synthases (CHSs) was investigated with a bioinformatics approach in the cephalochordate Branchiostoma floridae, in which the presence of chitin was initially reported in the skeletal rods of the pharyngeal gill basket. Twelve genes coding for proteins containing conserved amino acid residues of processive glycosyltransferases from GT2 family were found and 10 of them display mosaic structures with novel domains never reported previously in a chitin synthase. In particular, the presence of a discoidin (DS) and a sterile alpha motif (SAM) domain was found in nine identified proteins. Sequence analyses and homology modelling suggest that these domains might interact with the extracellular matrix and mediate protein-protein interaction. The multi-domain putative chitin synthases from B. floridae constitute an emblematic example of the explosion of domain innovation and shuffling which predate Metazoans.}, } @article {pmid23083808, year = {2012}, author = {Ramsdale, M}, title = {Programmed cell death in the cellular differentiation of microbial eukaryotes.}, journal = {Current opinion in microbiology}, volume = {15}, number = {6}, pages = {646-652}, doi = {10.1016/j.mib.2012.09.005}, pmid = {23083808}, issn = {1879-0364}, mesh = {*Apoptosis ; *Autophagy ; *Cell Differentiation ; Eukaryota/*physiology ; Signal Transduction ; }, abstract = {Programmed cell death (PCD) is a ubiquitous feature of multicellular and unicellular organisms. Eukaryotic microbes use PCD to regulate the development of specialized cells and structures. Many different types of PCD occur, ranging from apoptosis-like cell death, programmed necrosis and autophagic death. An overview of cell death pathways is undertaken, highlighting new elements in the PCD molecular machinery. Examples of PCD in cellular differentiation are explored alongside evolutionary scenarios that could initiate and maintain PCD in microbes, including the evolution of multicellularity. The finding that defects in PCD can lead to antimicrobial drug resistance is also considered. Greater understanding of PCD and its role in differentiation offers new hope for discovery of therapeutic agents that manipulate endogenous cell suicide pathways.}, } @article {pmid23077252, year = {2012}, author = {Sung, W and Ackerman, MS and Miller, SF and Doak, TG and Lynch, M}, title = {Drift-barrier hypothesis and mutation-rate evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {45}, pages = {18488-18492}, pmid = {23077252}, issn = {1091-6490}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Cell Division/genetics ; Chlamydomonas reinhardtii/*genetics ; Entomoplasmataceae/*genetics ; *Genetic Drift ; Genome Size/genetics ; Genome, Bacterial/genetics ; Genome, Plant/genetics ; *Models, Genetic ; *Mutation Rate ; *Reproductive Isolation ; Species Specificity ; }, abstract = {Mutation dictates the tempo and mode of evolution, and like all traits, the mutation rate is subject to evolutionary modification. Here, we report refined estimates of the mutation rate for a prokaryote with an exceptionally small genome and for a unicellular eukaryote with a large genome. Combined with prior results, these estimates provide the basis for a potentially unifying explanation for the wide range in mutation rates that exists among organisms. Natural selection appears to reduce the mutation rate of a species to a level that scales negatively with both the effective population size (N(e)), which imposes a drift barrier to the evolution of molecular refinements, and the genomic content of coding DNA, which is proportional to the target size for deleterious mutations. As a consequence of an expansion in genome size, some microbial eukaryotes with large N(e) appear to have evolved mutation rates that are lower than those known to occur in prokaryotes, but multicellular eukaryotes have experienced elevations in the genome-wide deleterious mutation rate because of substantial reductions in N(e).}, } @article {pmid23066508, year = {2012}, author = {Hadfield, MG}, title = {Molecular clue links bacteria to the origin of animals.}, journal = {eLife}, volume = {1}, number = {}, pages = {e00242}, pmid = {23066508}, issn = {2050-084X}, mesh = {Bacteroidetes/classification/*metabolism ; Biological Evolution ; Choanoflagellata/*drug effects/growth & development/ultrastructure ; Feeding Behavior ; Lipid Metabolism ; Lipids/biosynthesis/*pharmacology ; Morphogenesis/*drug effects ; Phylogeny ; }, abstract = {Bacteria have a role in the formation of colonies by a species of single-celled organisms whose ancestors gave rise to the animals, which suggests that bacteria might also have influenced the origin of multicellularity in animals.}, } @article {pmid23066504, year = {2012}, author = {Alegado, RA and Brown, LW and Cao, S and Dermenjian, RK and Zuzow, R and Fairclough, SR and Clardy, J and King, N}, title = {A bacterial sulfonolipid triggers multicellular development in the closest living relatives of animals.}, journal = {eLife}, volume = {1}, number = {}, pages = {e00013}, pmid = {23066504}, issn = {2050-084X}, support = {R01 GM086258/GM/NIGMS NIH HHS/United States ; F32 GM089018/GM/NIGMS NIH HHS/United States ; F32 GM086054/GM/NIGMS NIH HHS/United States ; T32 HG00047/HG/NHGRI NIH HHS/United States ; R01 GM099533/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteroidetes/classification/*metabolism ; Biological Evolution ; Choanoflagellata/*drug effects/growth & development/ultrastructure ; Feeding Behavior ; Lipid Metabolism ; Lipids/biosynthesis/*pharmacology ; Morphogenesis/*drug effects ; Phylogeny ; }, abstract = {Bacterially-produced small molecules exert profound influences on animal health, morphogenesis, and evolution through poorly understood mechanisms. In one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta, we find that rosette colony development is induced by the prey bacterium Algoriphagus machipongonensis and its close relatives in the Bacteroidetes phylum. Here we show that a rosette inducing factor (RIF-1) produced by A. machipongonensis belongs to the small class of sulfonolipids, obscure relatives of the better known sphingolipids that play important roles in signal transmission in plants, animals, and fungi. RIF-1 has extraordinary potency (femtomolar, or 10(-15) M) and S. rosetta can respond to it over a broad dynamic range-nine orders of magnitude. This study provides a prototypical example of bacterial sulfonolipids triggering eukaryotic morphogenesis and suggests molecular mechanisms through which bacteria may have contributed to the evolution of animals.DOI:http://dx.doi.org/10.7554/eLife.00013.001.}, } @article {pmid23066074, year = {2012}, author = {Newman, SA}, title = {Physico-genetic determinants in the evolution of development.}, journal = {Science (New York, N.Y.)}, volume = {338}, number = {6104}, pages = {217-219}, doi = {10.1126/science.1222003}, pmid = {23066074}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Body Patterning/*genetics ; Chimerism/embryology ; Cleavage Stage, Ovum ; Invertebrates/embryology ; Mutation ; *Physical Phenomena ; Vertebrates/embryology ; }, abstract = {Animal bodies and the embryos that generate them exhibit an assortment of stereotypic morphological motifs that first appeared more than half a billion years ago. During development, cells arrange themselves into tissues with interior cavities and multiple layers with immiscible boundaries, containing patterned arrangements of cell types. These tissues go on to elongate, fold, segment, and form appendages. Their motifs are similar to the outcomes of physical processes generic to condensed, chemically excitable, viscoelastic materials, although the embryonic mechanisms that generate them are typically much more complex. I propose that the origins of animal development lay in the mobilization of physical organizational effects that resulted when certain gene products of single-celled ancestors came to operate on the spatial scale of multicellular aggregates.}, } @article {pmid23058793, year = {2013}, author = {Karpov, SA and Mikhailov, KV and Mirzaeva, GS and Mirabdullaev, IM and Mamkaeva, KA and Titova, NN and Aleoshin, VV}, title = {Obligately phagotrophic aphelids turned out to branch with the earliest-diverging fungi.}, journal = {Protist}, volume = {164}, number = {2}, pages = {195-205}, doi = {10.1016/j.protis.2012.08.001}, pmid = {23058793}, issn = {1618-0941}, mesh = {Amino Acid Sequence ; Eukaryota/*classification/*genetics ; Evolution, Molecular ; Microalgae/parasitology ; Molecular Sequence Data ; *Phylogeny ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {Reconstructing the early evolution of fungi and metazoans, two of the kingdoms of multicellular eukaryotes thriving on earth, is a challenging task for biologists. Among extant organisms having characters intermediate between fungi and hypothetical protistan ancestors, from which both fungi and metazoans are believed to have evolved, aphelids are unfairly neglected. The phylogenetic position of these microalgal endoparasites remained uncertain, since no nucleotide sequence data have been reported to date. Aphelids resemble some primitive zoosporic fungi in life cycle, but, unlike fungi, they live by phagotrophy. Here we present a phylogeny, in which a cultured aphelid species, Amoeboaphelidium protococcarum, forms a monophyletic group with Rozella and microsporidia as a sister group to Fungi. We also report a non-canonical nuclear genetic code in A. protococcarum.}, } @article {pmid23057749, year = {2012}, author = {Mallarino, R and Abzhanov, A}, title = {Paths less traveled: evo-devo approaches to investigating animal morphological evolution.}, journal = {Annual review of cell and developmental biology}, volume = {28}, number = {}, pages = {743-763}, pmid = {23057749}, issn = {1530-8995}, support = {R21 DE021535/DE/NIDCR NIH HHS/United States ; 1R21DE021535-01/DE/NIDCR NIH HHS/United States ; }, mesh = {Adaptation, Biological/genetics ; Animal Fins/physiology ; Animals ; Beak/physiology ; *Biological Evolution ; Genetic Speciation ; Models, Biological ; Morphogenesis/*genetics ; Phylogeny ; }, abstract = {One of the chief aims of modern biology is to understand the causes and mechanisms of morphological evolution. Multicellular animals display a stunning diversity of shapes and sizes of their bodies and individual suborganismal structures, much of it important to their survival. What is the most efficient way to study the evolution of morphological diversity? The old-new field of evolutionary developmental biology (evo-devo) can be particularly useful for understanding the origins of animal forms, as it aims to consolidate advances from disparate fields such as phylogenetics, genomics, morphometrics, cell biology, and developmental biology. We analyze the structure of some of the most successful recent evo-devo studies, which we see as having three distinct but highly interdependent components: (a) morphometrics, (b) identification of candidate mechanisms, and (c) functional experiments. Our case studies illustrate how multifarious evo-devo approaches taken within the three-winged evo-devo research program explain developmental mechanisms for morphological evolution across different phylogenetic scales.}, } @article {pmid23056439, year = {2012}, author = {Saxer, G and Havlak, P and Fox, SA and Quance, MA and Gupta, S and Fofanov, Y and Strassmann, JE and Queller, DC}, title = {Whole genome sequencing of mutation accumulation lines reveals a low mutation rate in the social amoeba Dictyostelium discoideum.}, journal = {PloS one}, volume = {7}, number = {10}, pages = {e46759}, pmid = {23056439}, issn = {1932-6203}, support = {T15 LM007093/LM/NLM NIH HHS/United States ; 5T15LM007093-17/LM/NLM NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Dictyostelium/*genetics ; Genome/*genetics ; Mutation ; }, abstract = {Spontaneous mutations play a central role in evolution. Despite their importance, mutation rates are some of the most elusive parameters to measure in evolutionary biology. The combination of mutation accumulation (MA) experiments and whole-genome sequencing now makes it possible to estimate mutation rates by directly observing new mutations at the molecular level across the whole genome. We performed an MA experiment with the social amoeba Dictyostelium discoideum and sequenced the genomes of three randomly chosen lines using high-throughput sequencing to estimate the spontaneous mutation rate in this model organism. The mitochondrial mutation rate of 6.76×10(-9), with a Poisson confidence interval of 4.1×10(-9) - 9.5×10(-9), per nucleotide per generation is slightly lower than estimates for other taxa. The mutation rate estimate for the nuclear DNA of 2.9×10(-11), with a Poisson confidence interval ranging from 7.4×10(-13) to 1.6×10(-10), is the lowest reported for any eukaryote. These results are consistent with low microsatellite mutation rates previously observed in D. discoideum and low levels of genetic variation observed in wild D. discoideum populations. In addition, D. discoideum has been shown to be quite resistant to DNA damage, which suggests an efficient DNA-repair mechanism that could be an adaptation to life in soil and frequent exposure to intracellular and extracellular mutagenic compounds. The social aspect of the life cycle of D. discoideum and a large portion of the genome under relaxed selection during vegetative growth could also select for a low mutation rate. This hypothesis is supported by a significantly lower mutation rate per cell division in multicellular eukaryotes compared with unicellular eukaryotes.}, } @article {pmid23054553, year = {2012}, author = {Razeto-Barry, P}, title = {Autopoiesis 40 years later. A review and a reformulation.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {42}, number = {6}, pages = {543-567}, pmid = {23054553}, issn = {1573-0875}, mesh = {*Life ; Models, Biological ; }, abstract = {The concept of autopoiesis was proposed 40 years ago as a definition of a living being, with the aim of providing a unifying concept for biology. The concept has also been extended to the theory of knowledge and to different areas of the social and behavioral sciences. Given some ambiguities of the original definitions of autopoiesis, the concept has been criticized and has been interpreted in diverse and even contradictory ways, which has prevented its integration into the biological sciences where it originated. Here I present a critical review and conceptual analysis of the definition of autopoiesis, and propose a new definition that is more precise, clear, and concise than the original ones. I argue that the difficulty in understanding the term lies in its refined conceptual subtlety and not, as has been claimed by some authors, because it is a vacuous, trivial or very complex concept. I also relate the concept of autopoiesis to the concepts of closed systems, boundaries, homeostasis, self-reproduction, causal circularity, organization and multicellularity. I show that under my proposed definition the concept of a molecular autopoietic system is a good demarcation criterion of a living being, allowing its general integration into the biological sciences and enhancing its interdisciplinary use.}, } @article {pmid23053625, year = {2013}, author = {Funayama, N}, title = {The stem cell system in demosponges: suggested involvement of two types of cells: archeocytes (active stem cells) and choanocytes (food-entrapping flagellated cells).}, journal = {Development genes and evolution}, volume = {223}, number = {1-2}, pages = {23-38}, pmid = {23053625}, issn = {1432-041X}, mesh = {Animals ; Cell Differentiation ; Cell Movement ; Humans ; Porifera/*cytology ; *Stem Cells ; }, abstract = {Major questions about stem cell systems include what type(s) of stem cells are involved (unipotent/totipotent/pluripotent/multipotent stem cells) and how the self-renewal and differentiation of stem cells are regulated. Sponges, the sister group of all other animals and probably the earliest branching multicellular lineage of extant animals, are thought to possess totipotent stem cells. This review introduces what is known about the stem cells in sponges based on histological studies and also on recent molecular biological studies that have started to reveal the molecular and cellular mechanisms of the stem cell system in sponges (mainly in demosponges). The currently proposed model of the stem cell system in demosponges is described, and the possible applicability of this model to other classes of sponges is discussed. Finally, a possible scenario of the evolution of stem cells, including how migrating stem cells arose in the urmetazoan (the last common ancestor of metazoans) and the evolutionary origin of germ line cells in the urbilaterian (the last common ancestor of bilaterians), are discussed.}, } @article {pmid23046654, year = {2012}, author = {Cellier, MF}, title = {Nramp: from sequence to structure and mechanism of divalent metal import.}, journal = {Current topics in membranes}, volume = {69}, number = {}, pages = {249-293}, doi = {10.1016/B978-0-12-394390-3.00010-0}, pmid = {23046654}, issn = {1063-5823}, mesh = {Animals ; Bacteria/metabolism/pathogenicity ; Bacterial Proteins/chemistry/classification/metabolism ; Cation Transport Proteins/chemistry/classification/*metabolism ; Evolution, Molecular ; Ferrous Compounds/*metabolism ; Gene Expression Regulation ; Humans ; Iron Overload/metabolism/pathology ; Manganese/*metabolism ; Mice ; Parkinson Disease/metabolism/pathology ; Phylogeny ; Plasma Membrane Neurotransmitter Transport Proteins/chemistry/classification/metabolism ; Protein Structure, Tertiary ; Tuberculosis/genetics/metabolism/pathology ; }, abstract = {Mn and Fe are important for energy metabolism and oxidative stress resistance and cells maintain adequate stores for survival and prevention of toxicity. Membrane permeases of the natural resistance-associated macrophage protein (Nramp) family importing protons and divalent metals are conserved from bacteria to man. Nramp hydrophobic core relates structurally to a superfamily of cation-driven carriers with inverted symmetry. Molecular phylogeny and sequence features support Nramp pseudo-symmetric three-dimensional (3D) model, and remote ancestry to the LeuT superfamily. Genetic analyses suggest conservation of Nramp sequence marks the transition from a phylogenetic out-group and may relate to divalent metal selectivity. Three phylogroups of bacterial proton-dependent manganese transporters (MntH) demonstrate specific patterns of sequence conservation suggesting functional constraints linked to ecological or taxonomical distributions, which may contribute to bacterial virulence. Nramp 3D model is supported experimentally by transmembrane topology and structure-function studies of Escherichia coli and mouse homologs as well as peptide structure analyses. Eukaryotic Nramps are required for Mn and Fe homeostasis, contributing in multicellular organisms to subcellular and systemic metal traffic and intercellular signaling. Nramps are subjected to elaborate regulation including developmental control of gene expression, protein subcellular targeting, dynamic metallo-dependent control of messenger RNA and protein stability and trafficking. Several human pathologies may result from defects in Nramp-dependent Fe(2+) or Mn(2+) transport, including iron overload, neurodegenerative diseases and innate susceptibility to infectious diseases.}, } @article {pmid23046428, year = {2012}, author = {Yasumura, Y and Pierik, R and Fricker, MD and Voesenek, LA and Harberd, NP}, title = {Studies of Physcomitrella patens reveal that ethylene-mediated submergence responses arose relatively early in land-plant evolution.}, journal = {The Plant journal : for cell and molecular biology}, volume = {72}, number = {6}, pages = {947-959}, doi = {10.1111/tpj.12005}, pmid = {23046428}, issn = {1365-313X}, support = {BB/F020759/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Base Sequence ; Biological Evolution ; Bryopsida/*genetics/physiology ; Droughts ; Ethylenes/*metabolism ; *Gene Expression Regulation, Plant ; Molecular Sequence Data ; Mutation ; Phylogeny ; Plant Growth Regulators/*metabolism ; Plant Leaves/genetics/physiology ; Plant Proteins/*genetics ; Plant Shoots/genetics/physiology ; Receptors, Cell Surface/*genetics ; Sequence Analysis, DNA ; Stress, Physiological ; Water/physiology ; }, abstract = {Colonization of the land by multicellular green plants was a fundamental step in the evolution of life on earth. Land plants evolved from fresh-water aquatic algae, and the transition to a terrestrial environment required the acquisition of developmental plasticity appropriate to the conditions of water availability, ranging from drought to flood. Here we show that extant bryophytes exhibit submergence-induced developmental plasticity, suggesting that submergence responses evolved relatively early in the evolution of land plants. We also show that a major component of the bryophyte submergence response is controlled by the phytohormone ethylene, using a perception mechanism that has subsequently been conserved throughout the evolution of land plants. Thus a plant environmental response mechanism with major ecological and agricultural importance probably had its origins in the very earliest stages of the colonization of the land.}, } @article {pmid23045965, year = {2012}, author = {Edwards, J}, title = {Single-domain β-thymosins: the family history.}, journal = {Annals of the New York Academy of Sciences}, volume = {1269}, number = {}, pages = {7-15}, doi = {10.1111/j.1749-6632.2012.06684.x}, pmid = {23045965}, issn = {1749-6632}, mesh = {Amino Acid Sequence ; Animals ; Birds/genetics ; Evolution, Molecular ; Fishes/genetics ; Gene Duplication/genetics/physiology ; Molecular Sequence Data ; Reptiles/genetics ; Sequence Homology, Amino Acid ; Synteny/genetics ; Thymosin/chemistry/genetics/*metabolism ; Zebrafish/genetics ; }, abstract = {Evolution probably invented the β-thymosin domain in a single-celled close relative of multicellular animals. Expansion from single genes to the small family of monomeric β-thymosins of present-day vertebrates may have started with a very ancient duplication, before the rounds of whole-genome duplications. In land vertebrates and fish, this family consists of the descendants of five genes of their jawed vertebrate common ancestor. Identifying this common ancestry depends on the genes possessing conserved sets of flanking sequences, as the relationships are not recognizable from amino-acid sequences. One of these genes has given rise both to a group of fish β-thymosins and to a hitherto unrecognized group of β-thymosins of birds and reptiles. The resulting classification may prove useful in relation to the β-thymosins of model organisms, such as the zebrafish, and for identifying important noncoding sequence elements, exemplified here by a conserved sequence in the 3'untranslated region of transcripts from the β4 subfamily.}, } @article {pmid23037702, year = {2012}, author = {Watari, A}, title = {[Nature of cancer explored from the perspective of the functional evolution of proto-oncogenes].}, journal = {Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan}, volume = {132}, number = {10}, pages = {1165-1170}, doi = {10.1248/yakushi.12-00204}, pmid = {23037702}, issn = {1347-5231}, mesh = {Animals ; Biological Evolution ; Neoplasms/*genetics ; Oncogenes/physiology ; Proto-Oncogenes/*physiology ; p21-Activated Kinases/genetics ; }, abstract = {The products of proto-oncogene play critical roles in the development or maintenance of multicellular societies in animals via strict regulatory systems. When these regulatory systems are disrupted, proto-oncogenes can become oncogenes, and thereby induce cell transformation and carcinogenesis. To understand the molecular basis for development of the regulatory system of proto-oncogenes during evolution, we screened for ancestral proto-oncogenes from the unicellular choanoflagellate Monosiga ovata (M. ovata) by monitoring their transforming ability in mammalian cells; consequently, we isolated a Pak gene ortholog, which encodes a serine/threonine kinase as a 'primitive oncogene'. We also cloned Pak orthologs from fungi and the multicellular sponge Ephydatia fluviatilis, and compared their regulatory features with that of M. ovata Pak (MoPak). MoPak is constitutively active and induces cell transformation in mammalian cells. In contrast, Pak orthologs from multicellular animals are strictly regulated. Analyses of Pak mutants revealed that structural alterations in the auto-inhibitory domain (AID) are responsible for the enhanced kinase activity and the oncogenic activity of MoPak. Furthermore, we show that Rho family GTPases-mediated regulatory system of Pak kinase is conserved throughout the evolution from unicellular to multicellular animals, but the MoPak is more sensitive to the Rho family GTPases-mediated activation than multicellular Pak. These results show that maturation of AID function was required for the development of the strict regulatory system of the Pak proto-oncogene, and support the potential link between the development of the regulatory system of proto-oncogenes and the evolution of multicellularity. Further analysis of oncogenic functions of proto-oncogene orthologs in the unicellular genes would provide some insights into the mechanisms of the destruction of multicellular society in cancer.}, } @article {pmid23024606, year = {2012}, author = {Mallick, B and Ghosh, Z}, title = {Probing Evolutionary Biography of MicroRNAs and Associated Factors.}, journal = {Current genomics}, volume = {13}, number = {2}, pages = {144-152}, pmid = {23024606}, issn = {1875-5488}, abstract = {Intergenic DNA, often described as "playground of evolution", harbors a plethora of cis and trans regulatory elements in the form of non-coding RNAs (ncRNAs). The evolution of the silencing mechanism mediated by microRNAs (miRNAs), an important class of ncRNA, involves the proliferation of miRNA biogenesis and effector proteins, continuing innovation of novel families by the diversification of established families and spawning additional paralogous family members. Such evolving miRNA pathways for spatiotemporal regulation of the transcriptome have shaped the evolution of eukaryotic genomes and contributed to the complexity of multicellular organisms. Here, we focus on the emergence of new target specificity of the miRNAs along with the proliferation of core biogenesis and effector modules and show how this has contributed to generate diverse miRNA regulatory pathways.}, } @article {pmid23016975, year = {2012}, author = {Satoh, N and Tagawa, K and Takahashi, H}, title = {How was the notochord born?.}, journal = {Evolution & development}, volume = {14}, number = {1}, pages = {56-75}, doi = {10.1111/j.1525-142X.2011.00522.x}, pmid = {23016975}, issn = {1525-142X}, mesh = {Animals ; Body Patterning/genetics ; Chordata/embryology/*genetics/metabolism ; *Evolution, Molecular ; Fetal Proteins/genetics/metabolism ; Gastrula/embryology/metabolism ; Gene Expression Regulation, Developmental ; Genes, Developmental/genetics ; Invertebrates/embryology/genetics/metabolism ; Notochord/*embryology/metabolism ; Phylogeny ; T-Box Domain Proteins/genetics/metabolism ; Transcription, Genetic ; Wnt Signaling Pathway ; }, abstract = {More than 550 million years ago, chordates originated from a common ancestor shared with nonchordate deuterostomes by developing a novel type of larva, the "tadpole larva." The notochord is the supporting organ of the larval tail and the most prominent feature of chordates; indeed, phylum Chordata is named after this organ. In this review, we discuss the molecular mechanisms involved in the formation of the notochord over the course of chordate evolution with a special emphasis on a member of T-box gene family, Brachyury. Comparison of the decoded genome of a unicellular choanoflagellate with the genomes of sponge and cnidarians suggests that T-box gene family arose at the time of the evolution of multicellular animals. Gastrulation is a morphogenetic movement that is essential for the formation of two- or three-germ-layered embryos. Brachyury is transiently expressed in the blastopore (bp) region, where it confers on cells the ability to undergo invagination. This process is involved in the formation of the archenteron in all metazoans. This is a "primary" function of Brachyury. During the evolution of chordates, Brachyury gained an additional expression domain at the dorsal midline region of the bp. In this new expression domain, Brachyury served its "secondary" function, recruiting another set of target genes to form a dorsal axial organ, notochord. The Wnt/β-catenin, BMP/Nodal, and FGF-signaling pathways are involved in the transcriptional activation of Brachyury. We discuss the molecular mechanisms of Brachyury secondary function in the context of the dorsal-ventral (D-V) inversion theory and the aboral-dorsalization hypothesis. Although the scope of this review requires some degree of oversimplification of Brachyury function, it is beneficial to facilitate studies on the notochord formation, a central evolutionary developmental biology problem in the history of metazoan evolution, pointed out first by Alexander Kowalevsky.}, } @article {pmid23015456, year = {2013}, author = {Queller, DC and Strassmann, JE}, title = {Experimental evolution of multicellularity using microbial pseudo-organisms.}, journal = {Biology letters}, volume = {9}, number = {1}, pages = {20120636}, pmid = {23015456}, issn = {1744-957X}, mesh = {*Biological Evolution ; Biology/*methods ; Cell Lineage ; Cell Survival ; Cooperative Behavior ; *Models, Biological ; Models, Genetic ; Reproduction ; Selection, Genetic ; }, abstract = {In a major evolutionary transition to a new level of organization, internal conflicts must be controlled before the transition can truly be successful. One such transition is that from single cells to multicellularity. Conflicts among cells in multicellular organisms can be greatly reduced if they consist of genetically identical clones. However, mutations to cheaters that experience one round of within-individual selection could still be a problem, particularly for certain life cycles. We propose an experimental evolution method to investigate this issue, using micro-organisms to construct multicellular pseudo-organisms, which can be evolved under different artificial life cycles. These experiments can be used to test the importance of various life cycle features in maintaining cooperation. They include structured reproduction, in which small propagule size reduces within-individual genetic variation. They also include structured growth, which increases local relatedness within individual bodies. Our method provides a novel way to test how different life cycles favour cooperation, even for life cycles that do not exist.}, } @article {pmid23013032, year = {2012}, author = {Natochin, IuV and Felitsyn, SB and Klimova, EV and Shakhmatova, EI}, title = {[K+/Na+ in the animal extracellular fluid at weathering of granitoids and problem of the origin of life].}, journal = {Zhurnal evoliutsionnoi biokhimii i fiziologii}, volume = {48}, number = {4}, pages = {409-416}, pmid = {23013032}, issn = {0044-4529}, mesh = {Animals ; *Biological Evolution ; Eukaryota/chemistry/metabolism ; Extracellular Fluid/chemistry/metabolism ; Hemolymph/chemistry/metabolism ; *Origin of Life ; *Potassium/blood/chemistry/metabolism ; Prokaryotic Cells/chemistry/metabolism ; *Sodium/blood/chemistry/metabolism ; Water/chemistry ; }, abstract = {Leaching of granitoids of the paleoproterozoic age was performed from several seconds to 360 days in water solutions (pH < 6.0) in the oxygen or argon medium. Under these conditions the entrance of K+ into the solution has been shown to occur at the higher rate than that of Na+. The obtained data are considered as evidence in favor of a possibility of the existence at the earlier stages of the Earth geologic history of water reservoirs with predominance of K+ over Na+. The K+/Na+ ratio exceeding 1 has been shown in prokaryotes, in cells and tissues of the free living and parasitic species of invertebrate and vertebrate animals. At the same time in the extracellular fluid of the fresh water, marine, and terrestrial animals, in which the Na+ concentration varies from 13 to 482 mmol/l, the K+/Na+ ratio is preserved at the level of 0.034 +/- 0.001. These results are discussed in connection with the problem of origin of protocells and of concentration ratios of monovalent cations in water phases of multicellular organisms.}, } @article {pmid23002849, year = {2012}, author = {Lazar, EA and Mason, JK and MacPherson, RD and Srolovitz, DJ}, title = {Complete topology of cells, grains, and bubbles in three-dimensional microstructures.}, journal = {Physical review letters}, volume = {109}, number = {9}, pages = {095505}, doi = {10.1103/PhysRevLett.109.095505}, pmid = {23002849}, issn = {1079-7114}, mesh = {Cells/*ultrastructure ; Crystallization ; Models, Biological ; Models, Chemical ; *Models, Theoretical ; Particle Size ; Poisson Distribution ; }, abstract = {We introduce a general, efficient method to completely describe the topology of individual grains, bubbles, and cells in three-dimensional polycrystals, foams, and other multicellular microstructures. This approach is applied to a pair of three-dimensional microstructures that are often regarded as close analogues in the literature: one resulting from normal grain growth (mean curvature flow) and another resulting from a random Poisson-Voronoi tessellation of space. Grain growth strongly favors particular grain topologies, compared with the Poisson-Voronoi model. Moreover, the frequencies of highly symmetric grains are orders of magnitude higher in the grain growth microstructure than they are in the Poisson-Voronoi one. Grain topology statistics provide a strong, robust differentiator of different cellular microstructures and provide hints to the processes that drive different classes of microstructure evolution.}, } @article {pmid22999189, year = {2013}, author = {Celiker, H and Gore, J}, title = {Cellular cooperation: insights from microbes.}, journal = {Trends in cell biology}, volume = {23}, number = {1}, pages = {9-15}, doi = {10.1016/j.tcb.2012.08.010}, pmid = {22999189}, issn = {1879-3088}, support = {R00 GM085279/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/genetics ; *Biological Evolution ; *Cell Communication/genetics/physiology ; Mutation ; *Selection, Genetic ; }, abstract = {Cooperation between cells is a widespread phenomenon in nature, found across diverse systems ranging from microbial populations to multicellular organisms. For cooperation to evolve and be maintained within a population of cells, costs due to competition have to be outweighed by the benefits gained through cooperative actions. Because cooperation generally confers a cost to the cooperating cells, defector cells that do not cooperate but reap the benefits of cooperation can thrive and eventually drive the cooperating phenotypes to extinction. Here we summarize recent advances made in understanding how cooperation and multicellularity can evolve in microbial populations in the face of such conflicts and discuss parallels with cell populations within multicellular organisms.}, } @article {pmid22998625, year = {2013}, author = {Grinter, R and Milner, J and Walker, D}, title = {Beware of proteins bearing gifts: protein antibiotics that use iron as a Trojan horse.}, journal = {FEMS microbiology letters}, volume = {338}, number = {1}, pages = {1-9}, doi = {10.1111/1574-6968.12011}, pmid = {22998625}, issn = {1574-6968}, mesh = {Colicins/chemistry/*metabolism ; Ferredoxins/chemistry/*metabolism ; Iron/*metabolism ; Models, Molecular ; Pectobacterium/genetics/metabolism/*pathogenicity ; Plant Diseases/*microbiology ; }, abstract = {Multicellular organisms limit the availability of free iron to prevent the utilization of this essential nutrient by microbial pathogens. As such, bacterial pathogens possess a variety of mechanisms for obtaining iron from their hosts, including a number of examples of vertebrate pathogens that obtain iron directly from host proteins. Recently, two novel members of the colicin M bacteriocin family were discovered in Pectobacterium that suggest that this phytopathogen possesses such a system. These bacteriocins (pectocin M1 and M2) consist of a cytotoxic domain homologous to that of colicin M fused to a horizontally acquired plant-like ferredoxin. This ferredoxin domain substitutes the portion of colicin M required for receptor binding and translocation, presumably fulfilling this role by parasitizing an existing ferredoxin-based iron acquisition pathway. The ability of susceptible strains of Pectobacterium to utilize plant ferredoxin as an iron source was also demonstrated, providing additional evidence for the existence of such a system. If this hypothesis is correct, it represents the first example of iron piracy directly from a host protein by a phytopathogen and serves as a testament of the flexibility of evolution in creating new bacteriocin specificities.}, } @article {pmid22997518, year = {2012}, author = {Kotwal, GJ and Hatch, S and Marshall, WL}, title = {Viral infection: an evolving insight into the signal transduction pathways responsible for the innate immune response.}, journal = {Advances in virology}, volume = {2012}, number = {}, pages = {131457}, pmid = {22997518}, issn = {1687-8647}, support = {R01 AI070940/AI/NIAID NIH HHS/United States ; }, abstract = {The innate immune response is initiated by the interaction of stereotypical pathogen components with genetically conserved receptors for extracytosolic pathogen-associated molecular patterns (PAMPs) or intracytosolic nucleic acids. In multicellular organisms, this interaction typically clusters signal transduction molecules and leads to their activations, thereby initiating signals that activate innate immune effector mechanisms to protect the host. In some cases programmed cell death-a fundamental form of innate immunity-is initiated in response to genotoxic or biochemical stress that is associated with viral infection. In this paper we will summarize innate immune mechanisms that are relevant to viral pathogenesis and outline the continuing evolution of viral mechanisms that suppress the innate immunity in mammalian hosts. These mechanisms of viral innate immune evasion provide significant insight into the pathways of the antiviral innate immune response of many organisms. Examples of relevant mammalian innate immune defenses host defenses include signaling to interferon and cytokine response pathways as well as signaling to the inflammasome. Understanding which viral innate immune evasion mechanisms are linked to pathogenesis may translate into therapies and vaccines that are truly effective in eliminating the morbidity and mortality associated with viral infections in individuals.}, } @article {pmid22996257, year = {2013}, author = {Yang, C and Ye, Z}, title = {Trichomes as models for studying plant cell differentiation.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {70}, number = {11}, pages = {1937-1948}, pmid = {22996257}, issn = {1420-9071}, mesh = {Arabidopsis/*cytology/genetics/metabolism ; Cell Cycle/physiology ; *Cell Differentiation ; Cotton Fiber ; Gene Expression Regulation, Plant ; Models, Biological ; Plant Cells/metabolism/ultrastructure ; Plant Epidermis/*cytology/genetics/metabolism ; }, abstract = {Trichomes, originating from epidermal cells, are present on nearly all terrestrial plants. They exist in diverse forms, are readily accessible, and serve as an excellent model system for analyzing the molecular mechanisms in plant cell differentiation, including cell fate choices, cell cycle control, and cell morphogenesis. In Arabidopsis, two regulatory models have been identified that function in parallel in trichome formation; the activator-inhibitor model and the activator-depletion model. Cotton fiber, a similar unicellular structure, is controlled by some functional homologues of Arabidopsis trichome-patterning genes. Multicellular trichomes, as in tobacco and tomato, may form through a distinct pathway from unicellular trichomes. Recent research has shown that cell cycle control participates in trichome formation. In this review, we summarize the molecular mechanisms involved in the formation of unicellular and multicellular trichomes, and discuss the integration of the cell cycle in its initiation and morphogenesis.}, } @article {pmid22993722, year = {2012}, author = {Koonin, EV and Wolf, YI}, title = {Evolution of microbes and viruses: a paradigm shift in evolutionary biology?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {2}, number = {}, pages = {119}, pmid = {22993722}, issn = {2235-2988}, mesh = {Adaptation, Biological ; Archaea/*genetics ; Bacteria/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Genetic Variation ; Selection, Genetic ; Viruses/*genetics ; }, abstract = {When Charles Darwin formulated the central principles of evolutionary biology in the Origin of Species in 1859 and the architects of the Modern Synthesis integrated these principles with population genetics almost a century later, the principal if not the sole objects of evolutionary biology were multicellular eukaryotes, primarily animals and plants. Before the advent of efficient gene sequencing, all attempts to extend evolutionary studies to bacteria have been futile. Sequencing of the rRNA genes in thousands of microbes allowed the construction of the three- domain "ribosomal Tree of Life" that was widely thought to have resolved the evolutionary relationships between the cellular life forms. However, subsequent massive sequencing of numerous, complete microbial genomes revealed novel evolutionary phenomena, the most fundamental of these being: (1) pervasive horizontal gene transfer (HGT), in large part mediated by viruses and plasmids, that shapes the genomes of archaea and bacteria and call for a radical revision (if not abandonment) of the Tree of Life concept, (2) Lamarckian-type inheritance that appears to be critical for antivirus defense and other forms of adaptation in prokaryotes, and (3) evolution of evolvability, i.e., dedicated mechanisms for evolution such as vehicles for HGT and stress-induced mutagenesis systems. In the non-cellular part of the microbial world, phylogenomics and metagenomics of viruses and related selfish genetic elements revealed enormous genetic and molecular diversity and extremely high abundance of viruses that come across as the dominant biological entities on earth. Furthermore, the perennial arms race between viruses and their hosts is one of the defining factors of evolution. Thus, microbial phylogenomics adds new dimensions to the fundamental picture of evolution even as the principle of descent with modification discovered by Darwin and the laws of population genetics remain at the core of evolutionary biology.}, } @article {pmid22992464, year = {2012}, author = {Macro, L and Jaiswal, JK and Simon, SM}, title = {Dynamics of clathrin-mediated endocytosis and its requirement for organelle biogenesis in Dictyostelium.}, journal = {Journal of cell science}, volume = {125}, number = {Pt 23}, pages = {5721-5732}, pmid = {22992464}, issn = {1477-9137}, support = {R01 GM087977/GM/NIGMS NIH HHS/United States ; 5R01GM087977-03/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptor Protein Complex 2/metabolism ; Clathrin/*metabolism ; Dictyostelium/*cytology/*metabolism ; Endocytosis/*physiology ; Organelle Biogenesis ; Saccharomyces cerevisiae ; }, abstract = {The protein clathrin mediates one of the major pathways of endocytosis from the extracellular milieu and plasma membrane. In single-cell eukaryotes, such as Saccharomyces cerevisiae, the gene encoding clathrin is not an essential gene, raising the question of whether clathrin conveys specific advantages for multicellularity. Furthermore, in contrast to mammalian cells, endocytosis in S. cerevisiae is not dependent on either clathrin or adaptor protein 2 (AP2), an endocytic adaptor molecule. In this study, we investigated the requirement for components of clathrin-mediated endocytosis (CME) in another unicellular organism, the amoeba Dictyostelium. We identified a heterotetrameric AP2 complex in Dictyostelium that is similar to that which is found in higher eukaryotes. By simultaneously imaging fluorescently tagged clathrin and AP2, we found that, similar to higher eukaryotes, these proteins colocalized to membrane puncta that move into the cell together. In addition, the contractile vacuole marker protein, dajumin-green fluorescent protein (GFP), is trafficked via the cell membrane and internalized by CME in a clathrin-dependent, AP2-independent mechanism. This pathway is distinct from other endocytic mechanisms in Dictyostelium. Our finding that CME is required for the internalization of contractile vacuole proteins from the cell membrane explains the contractile vacuole biogenesis defect in Dictyostelium cells lacking clathrin. Our results also suggest that the machinery for CME and its role in organelle maintenance appeared early during eukaryotic evolution. We hypothesize that dependence of endocytosis on specific components of the CME pathway evolved later, as demonstrated by internalization independent of AP2 function.}, } @article {pmid22977115, year = {2013}, author = {Bezginov, A and Clark, GW and Charlebois, RL and Dar, VU and Tillier, ER}, title = {Coevolution reveals a network of human proteins originating with multicellularity.}, journal = {Molecular biology and evolution}, volume = {30}, number = {2}, pages = {332-346}, pmid = {22977115}, issn = {1537-1719}, mesh = {Animals ; *Biological Evolution ; Cell Communication/*physiology ; Ciliary Motility Disorders/genetics/metabolism ; Cluster Analysis ; Databases, Protein ; Female ; Gene Expression ; Humans ; Male ; Mutation ; Neoplasms/genetics/metabolism ; Protein Binding ; Protein Interaction Mapping ; Protein Interaction Maps ; Proteins/*genetics/*metabolism ; }, abstract = {Protein interaction networks play central roles in biological systems, from simple metabolic pathways through complex programs permitting the development of organisms. Multicellularity could only have arisen from a careful orchestration of cellular and molecular roles and responsibilities, all properly controlled and regulated. Disease reflects a breakdown of this organismal homeostasis. To better understand the evolution of interactions whose dysfunction may be contributing factors to disease, we derived the human protein coevolution network using our MatrixMatchMaker algorithm and using the Orthologous MAtrix project (OMA) database as a source for protein orthologs from 103 eukaryotic genomes. We annotated the coevolution network using protein-protein interaction data, many functional data sources, and we explored the evolutionary rates and dates of emergence of the proteins in our data set. Strikingly, clustering based only on the topology of the coevolution network partitions it into two subnetworks, one generally representing ancient eukaryotic functions and the other functions more recently acquired during animal evolution. That latter subnetwork is enriched for proteins with roles in cell-cell communication, the control of cell division, and related multicellular functions. Further annotation using data from genetic disease databases and cancer genome sequences strongly implicates these proteins in both ciliopathies and cancer. The enrichment for such disease markers in the animal network suggests a functional link between these coevolving proteins. Genetic validation corroborates the recruitment of ancient cilia in the evolution of multicellularity.}, } @article {pmid22977071, year = {2012}, author = {Booth, W and Smith, CF and Eskridge, PH and Hoss, SK and Mendelson, JR and Schuett, GW}, title = {Facultative parthenogenesis discovered in wild vertebrates.}, journal = {Biology letters}, volume = {8}, number = {6}, pages = {983-985}, pmid = {22977071}, issn = {1744-957X}, mesh = {Agkistrodon/*physiology ; Animals ; *Biological Evolution ; Female ; Gene Frequency ; Genotype ; Microsatellite Repeats/genetics ; North America ; Parthenogenesis/*physiology ; }, abstract = {Facultative parthenogenesis (FP)-asexual reproduction by bisexual species-has been documented in a variety of multi-cellular organisms but only recently in snakes, varanid lizards, birds and sharks. Unlike the approximately 80 taxa of unisexual reptiles, amphibians and fishes that exist in nature, FP has yet to be documented in the wild. Based on captive documentation, it appears that FP is widespread in squamate reptiles (snakes, lizards and amphisbaenians), and its occurrence in nature seems inevitable, yet the task of detecting FP in wild individuals has been deemed formidable. Here we show, using microsatellite DNA genotyping and litter characteristics, the first cases of FP in wild-collected pregnant females and their offspring of two closely related species of North American pitviper snakes-the copperhead (Agkistrodon contortrix) and cottonmouth (Agkistrodon piscivorus). Our findings support the view that non-hybrid origins of parthenogenesis, such as FP, are more common in squamates than previously thought. With this confirmation, FP can no longer be viewed as a rare curiosity outside the mainstream of vertebrate evolution. Future research on FP in squamate reptiles related to proximate control of induction, reproductive competence of parthenogens and population genetics modelling is warranted.}, } @article {pmid22975005, year = {2012}, author = {Niccoli, T and Partridge, L}, title = {Ageing as a risk factor for disease.}, journal = {Current biology : CB}, volume = {22}, number = {17}, pages = {R741-52}, doi = {10.1016/j.cub.2012.07.024}, pmid = {22975005}, issn = {1879-0445}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {*Aging ; Autophagy ; Cardiovascular Diseases/epidemiology/pathology ; DNA Damage ; Humans ; Life Expectancy ; Mitochondria/physiology ; Neoplasms/epidemiology/pathology ; Neurodegenerative Diseases/epidemiology/pathology ; Risk Factors ; Signal Transduction ; Time Factors ; }, abstract = {Age is the main risk factor for the prevalent diseases of developed countries: cancer, cardiovascular disease and neurodegeneration. The ageing process is deleterious for fitness, but can nonetheless evolve as a consequence of the declining force of natural selection at later ages, attributable to extrinsic hazards to survival: ageing can then occur as a side-effect of accumulation of mutations that lower fitness at later ages, or of natural selection in favour of mutations that increase fitness of the young but at the cost of a higher subsequent rate of ageing. Once thought of as an inexorable, complex and lineage-specific process of accumulation of damage, ageing has turned out to be influenced by mechanisms that show strong evolutionary conservation. Lowered activity of the nutrient-sensing insulin/insulin-like growth factor/Target of Rapamycin signalling network can extend healthy lifespan in yeast, multicellular invertebrates, mice and, possibly, humans. Mitochondrial activity can also promote ageing, while genome maintenance and autophagy can protect against it. We discuss the relationship between evolutionarily conserved mechanisms of ageing and disease, and the associated scientific challenges and opportunities.}, } @article {pmid22975003, year = {2012}, author = {Boehm, T}, title = {Evolution of vertebrate immunity.}, journal = {Current biology : CB}, volume = {22}, number = {17}, pages = {R722-32}, doi = {10.1016/j.cub.2012.07.003}, pmid = {22975003}, issn = {1879-0445}, mesh = {Adaptation, Physiological ; Animals ; *Biological Evolution ; Humans ; Immune System Diseases/epidemiology ; Immune System Phenomena ; Models, Immunological ; Vertebrates/*immunology ; }, abstract = {All multicellular organisms protect themselves against pathogens using sophisticated immune defenses. Functionally interconnected humoral and cellular facilities maintain immune homeostasis in the absence of overt infection and regulate the initiation and termination of immune responses directed against pathogens. Immune responses of invertebrates, such as flies, are innate and usually stereotyped; those of vertebrates, encompassing species as diverse as jawless fish and humans, are additionally adaptive, enabling more rapid and efficient immune reactivity upon repeated encounters with a pathogen. Many of the attributes historically defining innate and adaptive immunity are in fact common to both, blurring their functional distinction and emphasizing shared ancestry and co-evolution. These findings provide indications of the evolutionary forces underlying the origin of somatic diversification of antigen receptors and contribute to our understanding of the complex phenotypes of human immune disorders. Moreover, informed by phylogenetic considerations and inspired by improved knowledge of functional networks, new avenues emerge for innovative therapeutic strategies.}, } @article {pmid22970728, year = {2012}, author = {Yruela, I and Contreras-Moreira, B}, title = {Protein disorder in plants: a view from the chloroplast.}, journal = {BMC plant biology}, volume = {12}, number = {}, pages = {165}, pmid = {22970728}, issn = {1471-2229}, mesh = {Amino Acid Sequence ; Cell Nucleus/genetics/*metabolism ; Chloroplast Proteins/genetics/*metabolism ; Chloroplasts/genetics/*metabolism ; Computational Biology ; Evolution, Molecular ; *Genome, Plant ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; Nuclear Proteins/genetics/metabolism ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Plants/genetics/*metabolism ; Protein Transport ; Ribosomal Proteins/genetics/metabolism ; }, abstract = {BACKGROUND: The intrinsically unstructured state of some proteins, observed in all living organisms, is essential for basic cellular functions. In this field the available information from plants is limited but it has been reached a point where these proteins can be comprehensively classified on the basis of disorder, function and evolution.

RESULTS: Our analysis of plant genomes confirms that nuclear-encoded proteins follow the same trend than other multi-cellular eukaryotes; however, chloroplast- and mitochondria- encoded proteins conserve the patterns of Archaea and Bacteria, in agreement with their phylogenetic origin. Based on current knowledge about gene transference from the chloroplast to the nucleus, we report a strong correlation between the rate of disorder of transferred and nuclear-encoded proteins, even for polypeptides that play functional roles back in the chloroplast. We further investigate this trend by reviewing the set of chloroplast ribosomal proteins, one of the most representative transferred gene clusters, finding that the ribosomal large subunit, assembled from a majority of nuclear-encoded proteins, is clearly more unstructured than the small one, which integrates mostly plastid-encoded proteins.

CONCLUSIONS: Our observations suggest that the evolutionary dynamics of the plant nucleus adds disordered segments to genes alike, regardless of their origin, with the notable exception of proteins currently encoded in both genomes, probably due to functional constraints.}, } @article {pmid22970104, year = {2012}, author = {Hoef-Emden, K}, title = {Pitfalls of establishing DNA barcoding systems in protists: the cryptophyceae as a test case.}, journal = {PloS one}, volume = {7}, number = {8}, pages = {e43652}, pmid = {22970104}, issn = {1932-6203}, mesh = {Algorithms ; Base Sequence ; Bayes Theorem ; Cryptophyta/classification/*genetics ; Cyclooxygenase 1/genetics ; *DNA Barcoding, Taxonomic ; Likelihood Functions ; Models, Genetic ; Molecular Sequence Data ; Monte Carlo Method ; Phylogeny ; Ribosome Subunits, Large, Eukaryotic/genetics ; }, abstract = {A DNA barcode is a preferrably short and highly variable region of DNA supposed to facilitate a rapid identification of species. In many protistan lineages, a lack of species-specific morphological characters hampers an identification of species by light or electron microscopy, and difficulties to perform mating experiments in laboratory cultures also do not allow for an identification of biological species. Thus, testing candidate barcode markers as well as establishment of accurately working species identification systems are more challenging than in multicellular organisms. In cryptic species complexes the performance of a potential barcode marker can not be monitored using morphological characters as a feedback, but an inappropriate choice of DNA region may result in artifactual species trees for several reasons. Therefore a priori knowledge of the systematics of a group is required. In addition to identification of known species, methods for an automatic delimitation of species with DNA barcodes have been proposed. The Cryptophyceae provide a mixture of systematically well characterized as well as badly characterized groups and are used in this study to test the suitability of some of the methods for protists. As species identification method the performance of blast in searches against badly to well-sampled reference databases has been tested with COI-5P and 5'-partial LSU rDNA (domains A to D of the nuclear LSU rRNA gene). In addition the performance of two different methods for automatic species delimitation, fixed thresholds of genetic divergence and the general mixed Yule-coalescent model (GMYC), have been examined. The study demonstrates some pitfalls of barcoding methods that have to be taken care of. Also a best-practice approach towards establishing a DNA barcode system in protists is proposed.}, } @article {pmid22969411, year = {2012}, author = {Rabosky, DL and Slater, GJ and Alfaro, ME}, title = {Clade age and species richness are decoupled across the eukaryotic tree of life.}, journal = {PLoS biology}, volume = {10}, number = {8}, pages = {e1001381}, pmid = {22969411}, issn = {1545-7885}, mesh = {*Biodiversity ; Eukaryota/*classification ; Models, Biological ; *Phylogeny ; Species Specificity ; Time Factors ; }, abstract = {Explaining the dramatic variation in species richness across the tree of life remains a key challenge in evolutionary biology. At the largest phylogenetic scales, the extreme heterogeneity in species richness observed among different groups of organisms is almost certainly a function of many complex and interdependent factors. However, the most fundamental expectation in macroevolutionary studies is simply that species richness in extant clades should be correlated with clade age: all things being equal, older clades will have had more time for diversity to accumulate than younger clades. Here, we test the relationship between stem clade age and species richness across 1,397 major clades of multicellular eukaryotes that collectively account for more than 1.2 million described species. We find no evidence that clade age predicts species richness at this scale. We demonstrate that this decoupling of age and richness is unlikely to result from variation in net diversification rates among clades. At the largest phylogenetic scales, contemporary patterns of species richness are inconsistent with unbounded diversity increase through time. These results imply that a fundamentally different interpretative paradigm may be needed in the study of phylogenetic diversity patterns in many groups of organisms.}, } @article {pmid22965912, year = {2013}, author = {Basak, I and Møller, SG}, title = {Emerging facets of plastid division regulation.}, journal = {Planta}, volume = {237}, number = {2}, pages = {389-398}, pmid = {22965912}, issn = {1432-2048}, mesh = {Arabidopsis/chemistry/genetics ; Arabidopsis Proteins/*chemistry/genetics ; Cell Differentiation ; *Cell Division ; Chloroplast Proteins/chemistry/genetics ; Cytosol/chemistry ; Evolution, Molecular ; Intracellular Membranes/chemistry ; Multiprotein Complexes/chemistry/genetics ; Phosphorylation ; Plant Cells/chemistry ; Plastids/*chemistry/genetics ; }, abstract = {Plastids are complex organelles that are integrated into the plant host cell where they differentiate and divide in tune with plant differentiation and development. In line with their prokaryotic origin, plastid division involves both evolutionary conserved proteins and proteins of eukaryotic origin where the host has acquired control over the process. The plastid division apparatus is spatially separated between the stromal and the cytosolic space but where clear coordination mechanisms exist between the two machineries. Our knowledge of the plastid division process has increased dramatically during the past decade and recent findings have not only shed light on plastid division enzymology and the formation of plastid division complexes but also on the integration of the division process into a multicellular context. This review summarises our current knowledge of plastid division with an emphasis on biochemical features, the functional assembly of protein complexes and regulatory features of the overall process.}, } @article {pmid22962278, year = {2012}, author = {Simonin, A and Palma-Guerrero, J and Fricker, M and Glass, NL}, title = {Physiological significance of network organization in fungi.}, journal = {Eukaryotic cell}, volume = {11}, number = {11}, pages = {1345-1352}, pmid = {22962278}, issn = {1535-9786}, mesh = {Biological Transport ; Biomarkers/metabolism ; Carbon/metabolism ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Fluorescence ; Green Fluorescent Proteins/metabolism ; Histones/metabolism ; Hyphae/genetics/*physiology ; Isotope Labeling/methods ; *Metabolic Networks and Pathways ; Neurospora crassa/genetics/*physiology ; Nitrogen/metabolism ; Species Specificity ; Spores, Fungal/physiology ; Time Factors ; }, abstract = {The evolution of multicellularity has occurred in diverse lineages and in multiple ways among eukaryotic species. For plants and fungi, multicellular forms are derived from ancestors that failed to separate following cell division, thus retaining cytoplasmic continuity between the daughter cells. In networked organisms, such as filamentous fungi, cytoplasmic continuity facilitates the long-distance transport of resources without the elaboration of a separate vascular system. Nutrient translocation in fungi is essential for nutrient cycling in ecosystems, mycorrhizal symbioses, virulence, and substrate utilization. It has been proposed that an interconnected mycelial network influences resource translocation, but the theory has not been empirically tested. Here we show, by using mutants that disrupt network formation in Neurospora crassa (Δso mutant, no fusion; ΔPrm-1 mutant, ∼50% fusion), that the translocation of labeled nutrients is adversely affected in homogeneous environments and is even more severely impacted in heterogeneous environments. We also show that the ability to share resources and genetic exchange between colonies (via hyphal fusion) is very limited in mature colonies, in contrast to in young colonies and germlings that readily share nutrients and genetic resources. The differences in genetic/resource sharing between young and mature colonies were associated with variations in colony architecture (hyphal differentiation/diameters, branching patterns, and angles). Thus, the ability to share resources and genetic material between colonies is developmentally regulated and is a function of the age of a colony. This study highlights the necessity of hyphal fusion for efficient nutrient translocation within an N. crassa colony but also shows that established N. crassa colonies do not share resources in a significant manner.}, } @article {pmid22952431, year = {2012}, author = {Harmon, LJ}, title = {An inordinate fondness for eukaryotic diversity.}, journal = {PLoS biology}, volume = {10}, number = {8}, pages = {e1001382}, pmid = {22952431}, issn = {1545-7885}, mesh = {*Biodiversity ; Eukaryota/*genetics ; *Phylogeny ; }, abstract = {Why do some groups of organisms, like beetles, have so many species, and others, like the tuataras, so few? This classic question in evolutionary biology has a deep history and has been studied using both fossils and phylogenetic trees. Phylogeny-based studies have focused on tree balance, which compares the number of species across clades of the same age in the tree. These studies have suggested that rates of speciation and extinction vary tremendously across the tree of life. In this issue, Rabosky et al. report the most ambitious study to date on the differences in species diversity across clades in the tree of life. The authors bring together a tremendously large dataset of multicellular eukaryotes, including all living species of plants, animals, and fungi; they divide these organisms into 1,397 clades, accounting for more than 1.2 million species in total. Rabosky et al. find tremendous variation in diversity across the tree of life. There are old clades with few species, young clades with many species, and everything in between. They also note a peculiar aspect of their data: it is difficult or impossible to predict how many species will be found in a particular clade knowing how long a clade has been diversifying from a common ancestor. This pattern suggests complex dynamics of speciation and extinction in the history of eukaryotes. Rabosky et al.'s paper represents the latest development in our efforts to understand the Earth's biodiversity at the broadest scales.}, } @article {pmid22948853, year = {2012}, author = {Sun, S and Heitman, J}, title = {Should Y stay or should Y go: the evolution of non-recombining sex chromosomes.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {34}, number = {11}, pages = {938-942}, pmid = {22948853}, issn = {1521-1878}, support = {R37 AI039115/AI/NIAID NIH HHS/United States ; R01 AI039115/AI/NIAID NIH HHS/United States ; R37 AI39115/AI/NIAID NIH HHS/United States ; R01 AI50113/AI/NIAID NIH HHS/United States ; R01 AI050113/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/genetics ; Chromosomes, Human, Y/genetics ; *Evolution, Molecular ; Genetic Loci/genetics ; Humans ; Recombination, Genetic/*genetics ; Y Chromosome/*genetics ; }, abstract = {Gradual degradation seems inevitable for non-recombining sex chromosomes. This has been supported by the observation of degenerated non-recombining sex chromosomes in a variety of species. The human Y chromosome has also degenerated significantly during its evolution, and theories have been advanced that the Y chromosome could disappear within the next ~5 million years, if the degeneration rate it has experienced continues. However, recent studies suggest that this is unlikely. Conservative evolutionary forces such as strong purifying selection and intrachromosomal repair through gene conversion balance the degeneration tendency of the Y chromosome and maintain its integrity after an initial period of faster degeneration. We discuss the evidence both for and against the extinction of the Y chromosome. We also discuss potential insights gained on the evolution of sex-determining chromosomes by studying simpler sex-determining chromosomal regions of unicellular and multicellular microorganisms.}, } @article {pmid22948334, year = {2012}, author = {França, GS and Cancherini, DV and de Souza, SJ}, title = {Evolutionary history of exon shuffling.}, journal = {Genetica}, volume = {140}, number = {4-6}, pages = {249-257}, pmid = {22948334}, issn = {1573-6857}, mesh = {Animals ; Cluster Analysis ; Computational Biology/methods ; *Evolution, Molecular ; *Exons ; Humans ; Introns ; Open Reading Frames/genetics ; Plants/genetics ; Protein Interaction Domains and Motifs/genetics ; *Recombination, Genetic ; }, abstract = {Exon shuffling has been characterized as one of the major evolutionary forces shaping both the genome and the proteome of eukaryotes. This mechanism was particularly important in the creation of multidomain proteins during animal evolution, bringing a number of functional genetic novelties. Here, genome information from a variety of eukaryotic species was used to address several issues related to the evolutionary history of exon shuffling. By comparing all protein sequences within each species, we were able to characterize exon shuffling signatures throughout metazoans. Intron phase (the position of the intron regarding the codon) and exon symmetry (the pattern of flanking introns for a given exon or block of adjacent exons) were features used to evaluate exon shuffling. We confirmed previous observations that exon shuffling mediated by phase 1 introns (1-1 exon shuffling) is the predominant kind in multicellular animals. Evidence is provided that such pattern was achieved since the early steps of animal evolution, supported by a detectable presence of 1-1 shuffling units in Trichoplax adhaerens and a considerable prevalence of them in Nematostella vectensis. In contrast, Monosiga brevicollis, one of the closest relatives of metazoans, and Arabidopsis thaliana, showed no evidence of 1-1 exon or domain shuffling above what it would be expected by chance. Instead, exon shuffling events are less abundant and predominantly mediated by phase 0 introns (0-0 exon shuffling) in those non-metazoan species. Moreover, an intermediate pattern of 1-1 and 0-0 exon shuffling was observed for the placozoan T. adhaerens, a primitive animal. Finally, characterization of flanking intron phases around domain borders allowed us to identify a common set of symmetric 1-1 domains that have been shuffled throughout the metazoan lineage.}, } @article {pmid22945313, year = {2012}, author = {Moody, LA and Saidi, Y and Smiles, EJ and Bradshaw, SJ and Meddings, M and Winn, PJ and Coates, JC}, title = {ARABIDILLO gene homologues in basal land plants: species-specific gene duplication and likely functional redundancy.}, journal = {Planta}, volume = {236}, number = {6}, pages = {1927-1941}, pmid = {22945313}, issn = {1432-2048}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Arabidopsis/genetics ; Base Sequence ; Bryopsida/cytology/*genetics/growth & development ; Gene Expression Regulation, Plant ; Genes, Reporter ; Genome, Plant/*genetics ; Molecular Sequence Data ; Phenotype ; Phylogeny ; Plant Proteins/*genetics ; Plants, Genetically Modified ; Promoter Regions, Genetic/genetics ; Selaginellaceae/cytology/*genetics/growth & development ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Deletion ; Sequence Homology, Nucleic Acid ; Species Specificity ; }, abstract = {ARABIDILLO proteins regulate multicellular root development in Arabidopsis thaliana. Conserved ARABIDILLO homologues are present throughout land plants, even in early-evolving plants that do not possess complex root architecture, suggesting that ARABIDILLO genes have additional functions. Here, we have cloned and characterised ARABIDILLO gene homologues from two early-evolving land plants, the bryophyte Physcomitrella patens and the lycophyte Selaginella moellendorffii. We show that two of the PHYSCODILLO genes (PHYSCODILLO1A and -1B) exist as a tail-to-tail tandem array of two almost identical 12 kb sequences, while a third related gene (PHYSCODILLO2) is located elsewhere in the Physcomitrella genome. Physcomitrella possesses a very low percentage of tandemly arrayed genes compared with the later-evolving plants whose genomes have been sequenced to date. Thus, PHYSCODILLO1A and -1B genes represent a relatively unusual gene arrangement. PHYSCODILLO promoters are active largely in the haploid gametophyte, with additional activity at the foot of the sporophyte. The pattern of promoter activity is uniform in filamentous and leafy tissues, suggesting pleiotropic gene functions and likely functional redundancy: the latter possibility is confirmed by the lack of discernible phenotype in a physcodillo2 deletion mutant. Interestingly, the pattern of PHYSCODILLO promoter activity in female reproductive organs is strikingly similar to that of an Arabidopsis homologue, suggesting co-option of some PHYSCODILLO functions or regulation into both the sporophyte and gametophyte. In conclusion, our work identifies and characterises some of the earliest-evolving land plant ARABIDILLO homologues. We confirm that all land plant ARABIDILLO genes arose from a single common ancestor and suggest that PHYSCODILLO proteins have novel and pleiotropic functions, some of which may be conserved in later-evolving plants.}, } @article {pmid22933559, year = {2012}, author = {Lenhart, JS and Schroeder, JW and Walsh, BW and Simmons, LA}, title = {DNA repair and genome maintenance in Bacillus subtilis.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {76}, number = {3}, pages = {530-564}, pmid = {22933559}, issn = {1098-5557}, support = {T32 GM007544/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacillus subtilis/*genetics/growth & development/metabolism ; DNA Damage ; *DNA Repair ; *DNA Replication ; *Gene Expression Regulation, Bacterial ; Genome, Bacterial/*genetics ; Mutagenesis ; Spores, Bacterial/physiology ; }, abstract = {From microbes to multicellular eukaryotic organisms, all cells contain pathways responsible for genome maintenance. DNA replication allows for the faithful duplication of the genome, whereas DNA repair pathways preserve DNA integrity in response to damage originating from endogenous and exogenous sources. The basic pathways important for DNA replication and repair are often conserved throughout biology. In bacteria, high-fidelity repair is balanced with low-fidelity repair and mutagenesis. Such a balance is important for maintaining viability while providing an opportunity for the advantageous selection of mutations when faced with a changing environment. Over the last decade, studies of DNA repair pathways in bacteria have demonstrated considerable differences between Gram-positive and Gram-negative organisms. Here we review and discuss the DNA repair, genome maintenance, and DNA damage checkpoint pathways of the Gram-positive bacterium Bacillus subtilis. We present their molecular mechanisms and compare the functions and regulation of several pathways with known information on other organisms. We also discuss DNA repair during different growth phases and the developmental program of sporulation. In summary, we present a review of the function, regulation, and molecular mechanisms of DNA repair and mutagenesis in Gram-positive bacteria, with a strong emphasis on B. subtilis.}, } @article {pmid22930590, year = {2012}, author = {Dickinson, DJ and Nelson, WJ and Weis, WI}, title = {An epithelial tissue in Dictyostelium challenges the traditional origin of metazoan multicellularity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {34}, number = {10}, pages = {833-840}, pmid = {22930590}, issn = {1521-1878}, support = {R01 GM035527/GM/NIGMS NIH HHS/United States ; R37 GM035527/GM/NIGMS NIH HHS/United States ; GM035527/GM/NIGMS NIH HHS/United States ; R01 GM056169/GM/NIGMS NIH HHS/United States ; GM56169/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; *Cell Polarity ; Dictyostelium/*cytology ; Epithelial Cells/metabolism/*physiology ; Epithelium/metabolism ; Humans ; }, abstract = {We hypothesize that aspects of animal multicellularity originated before the divergence of metazoans from fungi and social amoebae. Polarized epithelial tissues are a defining feature of metazoans and contribute to the diversity of animal body plans. The recent finding of a polarized epithelium in the non-metazoan social amoeba Dictyostelium discoideum demonstrates that epithelial tissue is not a unique feature of metazoans, and challenges the traditional paradigm that multicellularity evolved independently in social amoebae and metazoans. An alternative view, presented here, is that the common ancestor of social amoebae, fungi, and animals spent a portion of its life cycle in a multicellular state and possessed molecular machinery necessary for forming an epithelial tissue. Some descendants of this ancestor retained multicellularity, while others reverted to unicellularity. This hypothesis makes testable predictions regarding tissue organization in close relatives of metazoans and provides a novel conceptual framework for studies of early animal evolution.}, } @article {pmid22928977, year = {2012}, author = {Jaiswal, P and Singh, SP and Aiyar, P and Akkali, R and Baskar, R}, title = {Regulation of multiple tip formation by caffeine in cellular slime molds.}, journal = {BMC developmental biology}, volume = {12}, number = {}, pages = {26}, pmid = {22928977}, issn = {1471-213X}, mesh = {1-Methyl-3-isobutylxanthine/pharmacology ; Caffeine/*pharmacology ; Cell Transdifferentiation ; Chemotactic Factors/pharmacology ; Chemotaxis ; Cyclic AMP/metabolism/physiology ; Cyclic Nucleotide Phosphodiesterases, Type 4/genetics/metabolism ; Dictyostelium/*cytology/drug effects/physiology ; Dipeptides/pharmacology ; Gene Expression ; Kinetics ; Lactams/pharmacology ; Phosphodiesterase 4 Inhibitors/*pharmacology ; Protozoan Proteins/genetics/metabolism ; }, abstract = {BACKGROUND: The multicellular slug in Dictyostelium has a single tip that acts as an organising centre patterning the rest of the slug. High adenosine levels at the tip are believed to be responsible for this tip dominance and the adenosine antagonist, caffeine overrides this dominance promoting multiple tip formation.

RESULTS: Caffeine induced multiple tip effect is conserved in all the Dictyostelids tested. Two key components of cAMP relay namely, cAMP phosphodiesterase (Pde4) and adenyl cyclase-A (AcaA) levels get reduced during secondary tip formation in Dictyostelium discoideum. Pharmacological inhibition of cAMP phosphodiesterase also resulted in multiple tips. Caffeine reduces cAMP levels by 16.4, 2.34, 4.71 and 6.30 folds, respectively in D. discoideum, D. aureostipes, D. minutum and Polysphondylium pallidum. We propose that altered cAMP levels, perturbed cAMP gradient and impaired signalling may be the critical factors for the origin of multiple tips in other Dictyostelids as well. In the presence of caffeine, slug cell movement gets impaired and restricted. The cell type specific markers, ecmA (prestalk) and pspA (prespore) cells are not equally contributing during additional tip formation. During additional tip emergence, prespore cells transdifferentiate to compensate the loss of prestalk cells.

CONCLUSION: Caffeine decreases adenyl cyclase-A (AcaA) levels and as a consequence low cAMP is synthesised altering the gradient. Further if cAMP phosphodiesterase (Pde4) levels go down in the presence of caffeine, the cAMP gradient breaks down. When there is no cAMP gradient, directional movement is inhibited and might favour re-differentiation of prespore to prestalk cells.}, } @article {pmid22926916, year = {2012}, author = {Chen, G and Rubinstein, B and Li, R}, title = {Whole chromosome aneuploidy: big mutations drive adaptation by phenotypic leap.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {34}, number = {10}, pages = {893-900}, pmid = {22926916}, issn = {1521-1878}, support = {R01 GM059964/GM/NIGMS NIH HHS/United States ; R01-GM059964/GM/NIGMS NIH HHS/United States ; }, mesh = {Abnormal Karyotype ; Adaptation, Biological/*genetics ; *Aneuploidy ; Animals ; Chromosomal Instability ; Chromosomes/*genetics ; *Evolution, Molecular ; Humans ; Mutagenesis ; Phenotype ; }, abstract = {Despite its widespread existence, the adaptive role of aneuploidy (the abnormal state of having an unequal number of different chromosomes) has been a subject of debate. Cellular aneuploidy has been associated with enhanced resistance to stress, whereas on the organismal level it is detrimental to multicellular species. Certain aneuploid karyotypes are deleterious for specific environments, but karyotype diversity in a population potentiates adaptive evolution. To reconcile these paradoxical observations, this review distinguishes the role of aneuploidy in cellular versus organismal evolution. Further, it proposes a population genetics perspective to examine the behavior of aneuploidy on a populational versus individual level. By altering the copy number of a significant portion of the genome, aneuploidy introduces large phenotypic leaps that enable small cell populations to explore a wide phenotypic landscape, from which adaptive traits can be selected. The production of chromosome number variation can be further increased by stress- or mutation-induced chromosomal instability, fueling rapid cellular adaptation.}, } @article {pmid22925839, year = {2012}, author = {Baars, BJ and Edelman, DB}, title = {Consciousness, biology and quantum hypotheses.}, journal = {Physics of life reviews}, volume = {9}, number = {3}, pages = {285-294}, doi = {10.1016/j.plrev.2012.07.001}, pmid = {22925839}, issn = {1873-1457}, mesh = {Animals ; Biology/*methods ; *Consciousness/physiology ; Evolution, Molecular ; Humans ; *Models, Neurological ; *Quantum Theory ; Wakefulness/physiology ; }, abstract = {Natural phenomena are reducible to quantum events in principle, but quantum mechanics does not always provide the best level of analysis. The many-body problem, chaotic avalanches, materials properties, biological organisms, and weather systems are better addressed at higher levels. Animals are highly organized, goal-directed, adaptive, selectionist, information-preserving, functionally redundant, multicellular, quasi-autonomous, highly mobile, reproducing, dissipative systems that conserve many fundamental features over remarkably long periods of time at the species level. Animal brains consist of massive, layered networks of specialized signaling cells with 10,000 communication points per cell, and interacting up to 1000 Hz. Neurons begin to divide and differentiate very early in gestation, and continue to develop until middle age. Waking brains operate far from thermodynamic equilibrium under delicate homeostatic control, making them extremely sensitive to a range of physical and chemical stimuli, highly adaptive, and able to produce a remarkable range of goal-relevant actions. Consciousness is "a difference that makes a difference" at the level of massive neuronal interactions in the most parallel-interactive anatomical structure of the mammalian brain, the cortico-thalamic (C-T) system. Other brain structures are not established to result in direct conscious experiences, at least in humans. However, indirect extra-cortical influences on the C-T system are pervasive. Learning, brain plasticity and major life adaptations may require conscious cognition. While brains evolved over hundreds of millions of years, and individual brains grow over months, years and decades, conscious events appear to have a duty cycle of ∼100 ms, fading after a few seconds. They can of course be refreshed by inner rehearsal, re-visualization, or attending to recurrent stimulus sources. These very distinctive brain events are needed when animals seek out and cope with new, unpredictable and highly valued life events, such as evading predators, gathering critical information, seeking mates and hunting prey. Attentional selection of conscious events can be observed behaviorally in animals showing coordinated receptor orienting, flexible responding, alertness, emotional reactions, seeking, motivation and curiosity, as well as behavioral surprise and cortical and autonomic arousal. Brain events corresponding to attentional selection are prominent and widespread. Attention generally results in conscious experiences, which may be needed to recruit widespread processing resources in the brain. Many neuronal processes never become conscious, such as the balance system of the inner ear. An air traveler may "see" the passenger cabin tilt downward as the plane tilts to descend for a landing. That visual experience occurs even at night, when the traveler has no external frame of spatial reference. The passenger's body tilt with respect to gravity is detected unconsciously via the hair cells of the vestibular canals, which act as liquid accelerometers. However, that sensory activity is not experienced directly. It only becomes conscious via vision and the body senses. The vestibular sense is therefore quite different from visual perception, which "reports" accurately to a conscious field of experience, so that we can point accurately to a bright star on a dark night. Vestibular input is also precise but unconscious. Conscious cognition is therefore a distinct kind of brain event. Many of its features are well established, and must be accounted for by any adequate theory. No non-biological examples are known. Penrose and Hameroff have proposed that consciousness may be viewed as a fundamental problem in quantum physics. Specifically, their 'orchestrated objective reduction' (Orch-OR) hypothesis posits that conscious states arise from quantum computations in the microtubules of neurons. However, a number of microtubule-associated proteins are found in both plant and animal cells (like neurons) and plants are not generally considered to be conscious. Current quantum-level proposals do not explain the prominent empirical features of consciousness. Notably, they do not distinguish between closely matched conscious and unconscious brain events, as cognitive-biological theories must. About half of the human brain does not support conscious contents directly, yet neurons in these "unconscious" brain regions contain large numbers of microtubules. QM phenomena are famously observer-dependent, but to the best of our knowledge it has not been shown that they require a conscious observer, as opposed to a particle detector. Conscious humans cannot detect quantum events "as such" without the aid of special instrumentation. Instead, we categorize the wavelengths of light into conscious sensory events that neglect their quantum mechanical properties. In science the burden of proof is on the proposer, and this burden has not yet been met by quantum-level proposals. While in the future we may discover quantum effects that bear distinctively on conscious cognition 'as such,' we do not have such evidence today.}, } @article {pmid22920514, year = {2012}, author = {Souza, V and Siefert, JL and Escalante, AE and Elser, JJ and Eguiarte, LE}, title = {The Cuatro Ciénegas Basin in Coahuila, Mexico: an astrobiological Precambrian Park.}, journal = {Astrobiology}, volume = {12}, number = {7}, pages = {641-647}, pmid = {22920514}, issn = {1557-8070}, mesh = {Biological Evolution ; *Ecosystem ; *Exobiology/methods ; Mexico ; Models, Biological ; Time Factors ; *Wilderness ; }, abstract = {The Cuatro Ciénegas Basin (CCB) is a rare oasis in the Chihuahuan Desert in the state of Coahuila, Mexico. It has a biological endemism similar to that of the Galapagos Islands, and its spring-fed ecosystems have very low nutrient content (nitrogen or phosphorous) and are dominated by diverse microbialites. Thus, it has proven to be a distinctive opportunity for the field of astrobiology, as the CCB can be seen as a proxy for an earlier time in Earth's history, in particular the late Precambrian, the biological frontier when prokaryotic life yielded at least partial dominance to eukaryotes and multicellular life. It is a kind of ecological time machine that provides abundant opportunities for collaborative investigations by geochemists, geologists, ecologists, and population biologists in the study of the evolutionary processes that structured Earth-based life, especially in the microbial realm. The CCB is an object of investigation for the identification of biosignatures of past and present biota that can be used in our search for extraterrestrial life. In this review, we summarize CCB research efforts that began with microbial ecology and population biology projects and have since been expanded into broader efforts that involve biogeochemistry, comparative genomics, and assessments of biosignatures. We also propose that, in the future, the CCB is sanctioned as a "Precambrian Park" for astrobiology.}, } @article {pmid22919645, year = {2012}, author = {Salvucci, E}, title = {Selfishness, warfare, and economics; or integration, cooperation, and biology.}, journal = {Frontiers in cellular and infection microbiology}, volume = {2}, number = {}, pages = {54}, pmid = {22919645}, issn = {2235-2988}, mesh = {Biology/*trends ; *Evolution, Molecular ; Humans ; }, abstract = {The acceptance of Darwin's theory of evolution by natural selection is not complete and it has been pointed out its limitation to explain the complex processes that constitute the transformation of species. It is necessary to discuss the explaining power of the dominant paradigm. It is common that new discoveries bring about contradictions that are intended to be overcome by adjusting results to the dominant reductionist paradigm using all sorts of gradations and combinations that are admitted for each case. In addition to the discussion on the validity of natural selection, modern findings represent a challenge to the interpretation of the observations with the Darwinian view of competition and struggle for life as theoretical basis. New holistic interpretations are emerging related to the Net of Life, in which the interconnection of ecosystems constitutes a dynamic and self-regulating biosphere: viruses are recognized as a macroorganism with a huge collection of genes, most unknown that constitute the major planet's gene pool. They play a fundamental role in evolution since their sequences are capable of integrating into the genomes in an "infective" way and become an essential part of multicellular organisms. They have content with "biological sense" i.e., they appear as part of normal life processes and have a serious role as carrier elements of complex genetic information. Antibiotics are cell signals with main effects on general metabolism and transcription on bacterial cells and communities. The hologenome theory considers an organism and all of its associated symbiotic microbes (parasites, mutualists, synergists, amensalists) as a result of symbiopoiesis. Microbes, helmints, that are normally understood as parasites are cohabitants and they have cohabited with their host and drive the evolution and existence of the partners. Each organism is the result of integration of complex systems. The eukaryotic organism is the result of combination of bacterial, virus, and eukaryotic DNA and it is the result of the interaction of its own genome with the genome of its microbiota, and their metabolism are intertwined (as a "superorganism") along evolution. The darwinian paradigm had its origin in the free market theories and concepts of Malthus and Spencer. Then, nature was explained on the basis of market theories moving away from an accurate explanation of natural phenomena. It is necessary to acknowledge the limitations of the dominant dogma. These new interpretations about biological processes, molecules, roles of viruses in nature, and microbial interactions are remarkable points to be considered in order to construct a solid theory adjusted to the facts and with less speculations and tortuous semantic traps.}, } @article {pmid22916027, year = {2012}, author = {Bietenhader, M and Martos, A and Tetaud, E and Aiyar, RS and Sellem, CH and Kucharczyk, R and Clauder-Münster, S and Giraud, MF and Godard, F and Salin, B and Sagot, I and Gagneur, J and Déquard-Chablat, M and Contamine, V and Hermann-Le Denmat, S and Sainsard-Chanet, A and Steinmetz, LM and di Rago, JP}, title = {Experimental relocation of the mitochondrial ATP9 gene to the nucleus reveals forces underlying mitochondrial genome evolution.}, journal = {PLoS genetics}, volume = {8}, number = {8}, pages = {e1002876}, pmid = {22916027}, issn = {1553-7404}, mesh = {Biological Evolution ; Cell Nucleus/enzymology/*genetics ; Fungal Proteins/*genetics/metabolism ; Gene Deletion ; Genes, Mitochondrial ; Genome, Mitochondrial ; Mitochondria/enzymology/*genetics ; Mitochondrial Proton-Translocating ATPases/*genetics/metabolism ; Oxidative Phosphorylation ; Podospora/enzymology/*genetics ; Protein Subunits/genetics/metabolism ; Saccharomyces cerevisiae/enzymology/*genetics ; Saccharomyces cerevisiae Proteins/*genetics/metabolism ; Transgenes ; }, abstract = {Only a few genes remain in the mitochondrial genome retained by every eukaryotic organism that carry out essential functions and are implicated in severe diseases. Experimentally relocating these few genes to the nucleus therefore has both therapeutic and evolutionary implications. Numerous unproductive attempts have been made to do so, with a total of only 5 successes across all organisms. We have taken a novel approach to relocating mitochondrial genes that utilizes naturally nuclear versions from other organisms. We demonstrate this approach on subunit 9/c of ATP synthase, successfully relocating this gene for the first time in any organism by expressing the ATP9 genes from Podospora anserina in Saccharomyces cerevisiae. This study substantiates the role of protein structure in mitochondrial gene transfer: expression of chimeric constructs reveals that the P. anserina proteins can be correctly imported into mitochondria due to reduced hydrophobicity of the first transmembrane segment. Nuclear expression of ATP9, while permitting almost fully functional oxidative phosphorylation, perturbs many cellular properties, including cellular morphology, and activates the heat shock response. Altogether, our study establishes a novel strategy for allotopic expression of mitochondrial genes, demonstrates the complex adaptations required to relocate ATP9, and indicates a reason that this gene was only transferred to the nucleus during the evolution of multicellular organisms.}, } @article {pmid22911953, year = {2012}, author = {Jonker, JL and von Byern, J and Flammang, P and Klepal, W and Power, AM}, title = {Unusual adhesive production system in the barnacle Lepas anatifera: an ultrastructural and histochemical investigation.}, journal = {Journal of morphology}, volume = {273}, number = {12}, pages = {1377-1391}, doi = {10.1002/jmor.20067}, pmid = {22911953}, issn = {1097-4687}, support = {P 21767/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Adhesives/chemistry/*isolation & purification/metabolism ; Animals ; Glycoproteins/biosynthesis/chemistry/*isolation & purification ; Secretory Pathway ; Thoracica/*chemistry/*cytology/ultrastructure ; }, abstract = {Adhesives that are naturally produced by marine organisms are potential sources of inspiration in the search for medical adhesives. Investigations of barnacle adhesives are at an early stage but it is becoming obvious that barnacles utilize a unique adhesive system compared to other marine organisms. The current study examined the fine structure and chemistry of the glandular system that produces the adhesive of the barnacle Lepas anatifera. All components for the glue originated from large single-cell glands (70-180 μm). Staining (including immunostaining) showed that L-3,4-dihydroxyphenylalanine and phosphoserine were not present in the glue producing tissues, demonstrating that the molecular adhesion of barnacles differs from all other permanently gluing marine animals studied to date. The glandular tissue and adhesive secretion primarily consisted of slightly acidic proteins but also included some carbohydrate. Adhesive proteins were stored in cytoplasmic granules adjacent to an intracellular drainage canal (ICC); observations implicated both merocrine and apocrine mechanisms in the transport of the secretion from the cell cytoplasm to the ICC. Inside the ICC, the secretion was no longer contained within granules but was a flocculent material which became "clumped" as it traveled through the canal network. Hemocytes were not seen within the adhesive "apparatus" (comprising of the glue producing cells and drainage canals), nor was there any structural mechanism by which additions such as hemocytes could be made to the secretion. The unicellular adhesive gland in barnacles is distinct from multicellular adhesive systems observed in marine animals such as mussels and tubeworms. Because the various components are not physically separated in the apparatus, the barnacle adhesive system appears to utilize completely different and unknown mechanisms for maintaining the liquid state of the glue within the body, as well as unidentified mechanisms for the conversion of extruded glue into hard cement.}, } @article {pmid22903534, year = {2012}, author = {Bosch, TC}, title = {Rethinking the origin of multicellularity: where do epithelia come from? (Comment on DOI 10.1002/bies.201100187).}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {34}, number = {10}, pages = {826-827}, doi = {10.1002/bies.201200104}, pmid = {22903534}, issn = {1521-1878}, mesh = {Animals ; *Cell Polarity ; Dictyostelium/*cytology ; Epithelial Cells/*physiology ; Humans ; }, } @article {pmid22889906, year = {2012}, author = {Jin, J and Pawson, T}, title = {Modular evolution of phosphorylation-based signalling systems.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {367}, number = {1602}, pages = {2540-2555}, pmid = {22889906}, issn = {1471-2970}, support = {MOP-13466//Canadian Institutes of Health Research/Canada ; MOP-57793//Canadian Institutes of Health Research/Canada ; MOP-6849//Canadian Institutes of Health Research/Canada ; }, mesh = {Allosteric Regulation ; Animals ; Binding Sites ; Enzyme Activation ; Eukaryota/chemistry/*enzymology ; *Evolution, Molecular ; Models, Molecular ; Phosphoric Monoester Hydrolases/chemistry ; *Phosphorylation ; Protein Binding ; Protein Kinases/*chemistry ; *Signal Transduction ; Substrate Specificity ; src Homology Domains ; }, abstract = {Phosphorylation sites are formed by protein kinases ('writers'), frequently exert their effects following recognition by phospho-binding proteins ('readers') and are removed by protein phosphatases ('erasers'). This writer-reader-eraser toolkit allows phosphorylation events to control a broad range of regulatory processes, and has been pivotal in the evolution of new functions required for the development of multi-cellular animals. The proteins that comprise this system of protein kinases, phospho-binding targets and phosphatases are typically modular in organization, in the sense that they are composed of multiple globular domains and smaller peptide motifs with binding or catalytic properties. The linkage of these binding and catalytic modules in new ways through genetic recombination, and the selection of particular domain combinations, has promoted the evolution of novel, biologically useful processes. Conversely, the joining of domains in aberrant combinations can subvert cell signalling and be causative in diseases such as cancer. Major inventions such as phosphotyrosine (pTyr)-mediated signalling that flourished in the first multi-cellular animals and their immediate predecessors resulted from stepwise evolutionary progression. This involved changes in the binding properties of interaction domains such as SH2 and their linkage to new domain types, and alterations in the catalytic specificities of kinases and phosphatases. This review will focus on the modular aspects of signalling networks and the mechanism by which they may have evolved.}, } @article {pmid22876786, year = {2012}, author = {Cohen, E and Chor, B}, title = {Detecting phylogenetic signals in eukaryotic whole genome sequences.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {19}, number = {8}, pages = {945-956}, doi = {10.1089/cmb.2012.0122}, pmid = {22876786}, issn = {1557-8666}, mesh = {Algorithms ; Animals ; *Computer Simulation ; Eukaryota/*genetics ; Genetic Speciation ; *Genome ; Humans ; *Models, Genetic ; *Phylogeny ; Proteome/genetics ; Reference Standards ; Sequence Homology, Nucleic Acid ; }, abstract = {Whole genome sequences are a rich source of molecular data, with a potential for the discovery of novel evolutionary information. Yet, many parts of these sequences are not known to be under evolutionary pressure and, thus, are not conserved. Furthermore, a good model for whole genome evolution does not exist. Consequently, it is not a priori clear if a meaningful phylogenetic signal exists and can be extracted from the sequences as a whole. Indeed, very few phylogenies were reconstructed based on these sequences. Prior to this work, only two reconstruction methods were applied to large eukaryotic genomes: the K(r) method (Haubold et al., 2009), which was applied to genomes of rather small diversity (Drosophila species), and the feature frequency profile method (Sims et al., 2009a), which was applied to genomes of moderate diversity (mammals). We investigate the whole genome-based phylogenetic reconstruction question with respect to a much wider taxonomic sample. We apply K(r), FFP, and an alternative alignment-free method, the average common subsequence (ACS) (Ulitsky et al., 2006), to 24 multicellular eukaryotes (vertebrates, invertebrates, and plants). We also apply ACS to the proteome sequences of these 24 taxa. We compare the resulting trees to a standard reference, the National Center for Biotechnology Information (NCBI) taxonomy tree. Trees produced by ACS(AA), based on proteomes, are in complete agreement with the NCBI tree. For the genome-based reconstruction, ACS(DNA) produces trees whose agreement with the NCBI tree is excellent to very good for divergence times up to 800 million years ago, medium at 1 billion years ago, and poor at 1.6 billion years ago. We conclude that whole genomes do carry a clear phylogenetic signal, yet this signal "saturates" with longer divergence times. Furthermore, from the few existing methods, ACS is best capable of detecting this signal.}, } @article {pmid22875808, year = {2012}, author = {Avesson, L and Reimegård, J and Wagner, EG and Söderbom, F}, title = {MicroRNAs in Amoebozoa: deep sequencing of the small RNA population in the social amoeba Dictyostelium discoideum reveals developmentally regulated microRNAs.}, journal = {RNA (New York, N.Y.)}, volume = {18}, number = {10}, pages = {1771-1782}, pmid = {22875808}, issn = {1469-9001}, mesh = {Amoebozoa/*genetics ; Animals ; Base Sequence ; Cluster Analysis ; Dictyostelium/*genetics/growth & development ; Gene Expression Regulation, Developmental ; Genome, Protozoan ; *High-Throughput Nucleotide Sequencing/methods ; MicroRNAs/chemistry/*genetics/isolation & purification ; Molecular Sequence Data ; Nucleic Acid Conformation ; RNA, Protozoan/genetics ; Transfection ; Validation Studies as Topic ; }, abstract = {The RNA interference machinery has served as a guardian of eukaryotic genomes since the divergence from prokaryotes. Although the basic components have a shared origin, silencing pathways directed by small RNAs have evolved in diverse directions in different eukaryotic lineages. Micro (mi)RNAs regulate protein-coding genes and play vital roles in plants and animals, but less is known about their functions in other organisms. Here, we report, for the first time, deep sequencing of small RNAs from the social amoeba Dictyostelium discoideum. RNA from growing single-cell amoebae as well as from two multicellular developmental stages was sequenced. Computational analyses combined with experimental data reveal the expression of miRNAs, several of them exhibiting distinct expression patterns during development. To our knowledge, this is the first report of miRNAs in the Amoebozoa supergroup. We also show that overexpressed miRNA precursors generate miRNAs and, in most cases, miRNA* sequences, whose biogenesis is dependent on the Dicer-like protein DrnB, further supporting the presence of miRNAs in D. discoideum. In addition, we find miRNAs processed from hairpin structures originating from an intron as well as from a class of repetitive elements. We believe that these repetitive elements are sources for newly evolved miRNAs.}, } @article {pmid22857779, year = {2012}, author = {Prem, D and Solís, MT and Bárány, I and Rodríguez-Sanz, H and Risueño, MC and Testillano, PS}, title = {A new microspore embryogenesis system under low temperature which mimics zygotic embryogenesis initials, expresses auxin and efficiently regenerates doubled-haploid plants in Brassica napus.}, journal = {BMC plant biology}, volume = {12}, number = {}, pages = {127}, pmid = {22857779}, issn = {1471-2229}, mesh = {Brassica napus/cytology/*embryology/genetics/growth & development ; *Cold Temperature ; DNA, Plant/analysis ; Desiccation ; Diploidy ; Germination ; Haploidy ; Indoleacetic Acids/*metabolism ; Pollen/cytology/*embryology/genetics/growth & development ; }, abstract = {BACKGROUND: Microspore embryogenesis represents a unique system of single cell reprogramming in plants wherein a highly specialized cell, the microspore, by specific stress treatment, switches its fate towards an embryogenesis pathway. In Brassica napus, a model species for this phenomenon, incubation of isolated microspores at 32°C is considered to be a pre-requisite for embryogenesis induction.

RESULTS: We have developed a new in vitro system at lower temperature (18°C) to efficiently induce microspore embryogenesis throughout two different developmental pathways: one involving the formation of suspensor-like structures (52.4%) and another producing multicellular embryos without suspensor (13.1%); additionally, a small proportion of non-responsive microspores followed a gametophytic-like development (34.4%) leading to mature pollen. The suspensor-like pathway followed at 18°C involved the establishment of asymmetric identities from the first microspore division and an early polarity leading to different cell fates, suspensor and embryo development, which were formed by cells with different organizations and endogenous auxin distribution, similar to zygotic embryogenesis. In addition, a new strategy for germination of microspore derived embryos was developed for achieving more than 90% conversion of embryos to plantlets, with a predominance of spontaneous doubled haploids plants.

CONCLUSION: The present work reveals a novel mechanism for efficient microspore embryogenesis induction in B. napus using continuous low temperature treatment. Results indicated that low temperature applied for longer periods favours an embryogenesis pathway whose first division originates asymmetric cell identities, early polarity establishment and the formation of suspensor-like structures, mimicking zygotic embryogenesis. This new in vitro system provides a convenient tool to analyze in situ the mechanisms underlying different developmental pathways during the microspore reprogramming, breaking or not the cellular symmetry, the establishment of polarity and the developmental embryo patterning, which further produce mature embryos and plants.}, } @article {pmid22857263, year = {2012}, author = {Sterkers, Y and Lachaud, L and Bourgeois, N and Crobu, L and Bastien, P and Pagès, M}, title = {Novel insights into genome plasticity in Eukaryotes: mosaic aneuploidy in Leishmania.}, journal = {Molecular microbiology}, volume = {86}, number = {1}, pages = {15-23}, doi = {10.1111/j.1365-2958.2012.08185.x}, pmid = {22857263}, issn = {1365-2958}, mesh = {Adaptation, Biological ; *Aneuploidy ; Evolution, Molecular ; Genetic Heterogeneity ; Genome Size ; *Genome, Protozoan ; Genomic Instability ; Leishmania/*genetics ; }, abstract = {Leishmania are unicellular eukaryotes that have many markedly original molecular features compared with other uni- or multicellular eukaryotes like yeasts or mammals. Genome plasticity in this parasite has been the subject of many publications, and has been associated with drug resistance or adaptability. Aneuploidy has been suspected by several authors and it is now confirmed using state-of-the-art technologies such as high-throughput DNA sequencing. The analysis of genome contents at the single cell level using fluorescence in situ hybridization (FISH) has brought a new light on the genome organization: within a cell population, every chromosome, in every cell, may be present in at least two ploidy states (being either monosomic, disomic or trisomic), and the chromosomal content varies greatly from cell to cell, thus generating a constitutive intra-strain genomic heterogeneity, here termed 'mosaic aneuploidy'. Mosaic aneuploidy deeply affects the genetics of these organisms, leading, for example, to an extreme degree of intra-strain genomic diversity, as well as to a clearance of heterozygous cells in the population without however affecting genetic heterogeneity. Second, mosaic aneuploidy might be considered as a powerful strategy evolved by the parasite for adapting to modifications of environment conditions as well as for the emergence of drug resistance. On the whole, mosaic aneuploidy may be considered as a novel mechanism for generating phenotypic diversity driven by genomic plasticity.}, } @article {pmid22855327, year = {2012}, author = {Galliot, B}, title = {Preface: the hydra model system.}, journal = {The International journal of developmental biology}, volume = {56}, number = {6-8}, pages = {407-409}, doi = {10.1387/ijdb.120094bg}, pmid = {22855327}, issn = {1696-3547}, mesh = {Animals ; *Hydra/physiology ; Models, Animal ; Models, Biological ; Regeneration ; }, abstract = {The freshwater Hydra polyp emerged as a model system in 1741 when Abraham Trembley not only discovered its amazing regenerative potential, but also demonstrated that experimental manipulations pave the way to research in biology. Since then, Hydra flourished as a potent and fruitful model system to help answer questions linked to cell and developmental biology, as such as the setting up of an organizer to regenerate a complex missing structure, the establishment and maintainance of polarity in a multicellular organism, the development of mathematical models to explain the robust developmental rules observed in this animal, the maintainance of stemness and multipotency in a highly dynamic environment, the plasticity of differentiated cells, to name but a few. However the Hydra model system is not restricted to cell and developmental biology; during the past 270 years it has also been heavily used to investigate the relationships between Hydra and its environment, opening new horizons concerning neurophysiology, innate immunity, ecosystems, ecotoxicology, symbiosis...}, } @article {pmid22842779, year = {2012}, author = {Schippers, JH and Nguyen, HM and Lu, D and Schmidt, R and Mueller-Roeber, B}, title = {ROS homeostasis during development: an evolutionary conserved strategy.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {69}, number = {19}, pages = {3245-3257}, pmid = {22842779}, issn = {1420-9071}, mesh = {Animals ; *Biological Evolution ; Cell Differentiation ; Cell Proliferation ; Glutaredoxins/metabolism ; *Growth and Development ; Homeostasis ; NADPH Oxidases/metabolism ; Plants/metabolism ; Proteins/metabolism ; Reactive Oxygen Species/*metabolism ; Signal Transduction ; Thioredoxins/metabolism ; Yeasts/metabolism ; }, abstract = {The balance between cellular proliferation and differentiation is a key aspect of development in multicellular organisms. Recent studies on Arabidopsis roots revealed distinct roles for different reactive oxygen species (ROS) in these processes. Modulation of the balance between ROS in proliferating cells and elongating cells is controlled at least in part at the transcriptional level. The effect of ROS on proliferation and differentiation is not specific for plants but appears to be conserved between prokaryotic and eukaryotic life forms. The ways in which ROS is received and how it affects cellular functioning is discussed from an evolutionary point of view. The different redox-sensing mechanisms that evolved ultimately result in the activation of gene regulatory networks that control cellular fate and decision-making. This review highlights the potential common origin of ROS sensing, indicating that organisms evolved similar strategies for utilizing ROS during development, and discusses ROS as an ancient universal developmental regulator.}, } @article {pmid22837400, year = {2012}, author = {Nichols, SA and Roberts, BW and Richter, DJ and Fairclough, SR and King, N}, title = {Origin of metazoan cadherin diversity and the antiquity of the classical cadherin/β-catenin complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {32}, pages = {13046-13051}, pmid = {22837400}, issn = {1091-6490}, support = {R01 GM089977/GM/NIGMS NIH HHS/United States ; T32 GM007232/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Cadherins/*genetics ; Choanoflagellata/*genetics ; Computational Biology ; DNA Primers/genetics ; *Evolution, Molecular ; *Genetic Variation ; Genome/genetics ; Genomic Library ; Molecular Sequence Data ; *Phylogeny ; Sequence Analysis, DNA ; beta Catenin/*genetics ; }, abstract = {The evolution of cadherins, which are essential for metazoan multicellularity and restricted to metazoans and their closest relatives, has special relevance for understanding metazoan origins. To reconstruct the ancestry and evolution of cadherin gene families, we analyzed the genomes of the choanoflagellate Salpingoeca rosetta, the unicellular outgroup of choanoflagellates and metazoans Capsaspora owczarzaki, and a draft genome assembly from the homoscleromorph sponge Oscarella carmela. Our finding of a cadherin gene in C. owczarzaki reveals that cadherins predate the divergence of the C. owczarzaki, choanoflagellate, and metazoan lineages. Data from these analyses also suggest that the last common ancestor of metazoans and choanoflagellates contained representatives of at least three cadherin families, lefftyrin, coherin, and hedgling. Additionally, we find that an O. carmela classical cadherin has predicted structural features that, in bilaterian classical cadherins, facilitate binding to the cytoplasmic protein β-catenin and, thereby, promote cadherin-mediated cell adhesion. In contrast with premetazoan cadherin families (i.e., those conserved between choanoflagellates and metazoans), the later appearance of classical cadherins coincides with metazoan origins.}, } @article {pmid22833122, year = {2012}, author = {Aoyama, T and Hiwatashi, Y and Shigyo, M and Kofuji, R and Kubo, M and Ito, M and Hasebe, M}, title = {AP2-type transcription factors determine stem cell identity in the moss Physcomitrella patens.}, journal = {Development (Cambridge, England)}, volume = {139}, number = {17}, pages = {3120-3129}, doi = {10.1242/dev.076091}, pmid = {22833122}, issn = {1477-9129}, mesh = {Arabidopsis Proteins/*metabolism ; Blotting, Southern ; Bryopsida/*cytology/*genetics/growth & development ; Cell Differentiation/*physiology ; Cluster Analysis ; Computational Biology ; Cytokinins/metabolism ; Gene Expression Regulation, Plant/*genetics ; Germ Cells, Plant/growth & development ; Histocytochemistry ; Indoleacetic Acids/metabolism ; Likelihood Functions ; Microscopy, Fluorescence ; Models, Genetic ; Phylogeny ; Plasmids/genetics ; Real-Time Polymerase Chain Reaction ; Species Specificity ; Stem Cells/*physiology ; Transcription Factors/*metabolism ; }, abstract = {Stem cells are formed at particular times and positions during the development of multicellular organisms. Whereas flowering plants form stem cells only in the sporophyte generation, non-seed plants form stem cells in both the sporophyte and gametophyte generations. Although the molecular mechanisms underlying stem cell formation in the sporophyte generation have been extensively studied, only a few transcription factors involved in the regulation of gametophyte stem cell formation have been reported. The moss Physcomitrella patens forms a hypha-like body (protonema) and a shoot-like body (gametophore) from a protonema apical cell and a gametophore apical cell, respectively. These apical cells have stem cell characteristics and are formed as side branches of differentiated protonema cells. Here, we show that four AP2-type transcription factors orthologous to Arabidopsis thaliana AINTEGUMENTA, PLETHORA and BABY BOOM (APB) are indispensable for the formation of gametophore apical cells from protonema cells. Quadruple disruption of all APB genes blocked gametophore formation, even in the presence of cytokinin, which enhances gametophore apical cell formation in the wild type. All APB genes were expressed in emerging gametophore apical cells, but not in protonema apical cells. Heat-shock induction of an APB4 transgene driven by a heat-shock promoter increased the number of gametophores. Expression of all APB genes was induced by auxin but not by cytokinin. Thus, the APB genes function synergistically with cytokinin signaling to determine the identity of the two types of stem cells.}, } @article {pmid22832104, year = {2012}, author = {Sebé-Pedrós, A and Zheng, Y and Ruiz-Trillo, I and Pan, D}, title = {Premetazoan origin of the hippo signaling pathway.}, journal = {Cell reports}, volume = {1}, number = {1}, pages = {13-20}, pmid = {22832104}, issn = {2211-1247}, support = {/HHMI_/Howard Hughes Medical Institute/United States ; 206883/ERC_/European Research Council/International ; R01 EY015708/EY/NEI NIH HHS/United States ; R01EY015708/EY/NEI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Amoeba/metabolism ; Animals ; Drosophila melanogaster/genetics/growth & development/metabolism ; *Evolution, Molecular ; Gene Expression Regulation ; Genomics ; Likelihood Functions ; Molecular Sequence Data ; Protein Serine-Threonine Kinases/chemistry/*genetics/metabolism ; Sequence Alignment ; Signal Transduction/*genetics ; Transcription Factors/metabolism ; }, abstract = {Nonaggregative multicellularity requires strict control of cell number. The Hippo signaling pathway coordinates cell proliferation and apoptosis and is a central regulator of organ size in animals. Recent studies have shown the presence of key members of the Hippo pathway in nonbilaterian animals, but failed to identify this pathway outside Metazoa. Through comparative analyses of recently sequenced holozoan genomes, we show that Hippo pathway components, such as the kinases Hippo and Warts, the coactivator Yorkie, and the transcription factor Scalloped, were already present in the unicellular ancestors of animals. Remarkably, functional analysis of Hippo components of the amoeboid holozoan Capsaspora owczarzaki, performed in Drosophila melanogaster, demonstrate that the growth-regulatory activity of the Hippo pathway is conserved in this unicellular lineage. Our findings show that the Hippo pathway evolved well before the origin of Metazoa and highlight the importance of Hippo signaling as a key developmental mechanism predating the origin of Metazoa.}, } @article {pmid22826714, year = {2012}, author = {Cvrčková, F and Grunt, M and Bezvoda, R and Hála, M and Kulich, I and Rawat, A and Zárský, V}, title = {Evolution of the land plant exocyst complexes.}, journal = {Frontiers in plant science}, volume = {3}, number = {}, pages = {159}, pmid = {22826714}, issn = {1664-462X}, abstract = {Exocyst is an evolutionarily conserved vesicle tethering complex functioning especially in the last stage of exocytosis. Homologs of its eight canonical subunits - Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84 - were found also in higher plants and confirmed to form complexes in vivo, and to participate in cell growth including polarized expansion of pollen tubes and root hairs. Here we present results of a phylogenetic study of land plant exocyst subunits encoded by a selection of completely sequenced genomes representing a variety of plant, mostly angiosperm, lineages. According to their evolution histories, plant exocyst subunits can be divided into several groups. The core subunits Sec6, Sec8, and Sec10, together with Sec3 and Sec5, underwent few, if any fixed duplications in the tracheophytes (though they did amplify in the moss Physcomitrella patens), while others form larger families, with the number of paralogs ranging typically from two to eight per genome (Sec15, Exo84) to several dozens per genome (Exo70). Most of the diversity, which can be in some cases traced down to the origins of land plants, can be attributed to the peripheral subunits Exo84 and, in particular, Exo70. As predicted previously, early land plants (including possibly also the Rhyniophytes) encoded three ancestral Exo70 paralogs which further diversified in the course of land plant evolution. Our results imply that plants do not have a single "Exocyst complex" - instead, they appear to possess a diversity of exocyst variants unparalleled among other organisms studied so far. This feature might perhaps be directly related to the demands of building and maintenance of the complicated and spatially diverse structures of the endomembranes and cell surfaces in multicellular land plants.}, } @article {pmid22825600, year = {2012}, author = {Chakraborty, C and Agoramoorthy, G}, title = {Stem cells in the light of evolution.}, journal = {The Indian journal of medical research}, volume = {135}, number = {6}, pages = {813-819}, pmid = {22825600}, issn = {0971-5916}, mesh = {Animals ; *Biological Evolution ; Gene Regulatory Networks ; Humans ; Mammals ; *Regenerative Medicine ; Selection, Genetic ; *Stem Cells/cytology/physiology ; }, abstract = {All organisms depend on stem cells for their survival. As a result, stem cells may be a prerequisite for the evolution of specific characteristics in organisms that include regeneration, multicellularity and coloniality. Stem cells have attracted the attention of biologists and medical scientists for a long time. These provide materials for regenerative medicine. We review in this paper, the link between modern stem cell research and early studies in ancient organisms. It also outlines details on stem cells in the light of evolution with an emphasis on their regeneration potential, coloniality and multicellularity. The information provided might be of use to molecular biologists, medical scientists and developmental biologists who are engaged in integrated research involving the stem cells.}, } @article {pmid22821454, year = {2012}, author = {Sommer, RJ}, title = {Evolution of regulatory networks: nematode vulva induction as an example of developmental systems drift.}, journal = {Advances in experimental medicine and biology}, volume = {751}, number = {}, pages = {79-91}, doi = {10.1007/978-1-4614-3567-9_4}, pmid = {22821454}, issn = {0065-2598}, mesh = {Animals ; Biological Evolution ; Caenorhabditis elegans/genetics/*growth & development/metabolism ; Cell Communication ; Conserved Sequence ; Epidermis/*growth & development/metabolism ; Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Helminth Proteins/genetics/metabolism ; Larva/genetics/*growth & development/metabolism ; Nematoda/genetics/*growth & development/metabolism ; Phenotype ; Phylogeny ; Reproduction/physiology ; Signal Transduction ; }, abstract = {Changes in the developmental processes and developmental mechanisms can result in the modification of morphological structures and in the evolution of phenotypic novelty. But how do developmental processes evolve? One striking finding in modern biology is the confrontation of morphological diversity in multicellular organisms with the conserved blueprint of life-the small number of conserved signaling pathways and transcriptional regulators. Evolutionary developmental biology (evo-devo) tries to explain this discrepancy between macroscopic diversity and molecular uniformity. Selected case studies in evo-devo models allowed detailed insight into the mechanisms of evolutionary changes and might help solving this problem. Here, I compare the formation of vulva development between Caenorhabditis elegans and the evo-devo model Pristionchus pacificus. More than 3 decades of work in C. elegans and 15 years in P. pacificus provide an insight into the molecular mechanisms of developmental change during vulva evolution. C. elegans and P. pacificus differ first, in the type of the signaling system used for vulva induction; second, the cells required for the inductive interactions; third, the logic of the signal system, and finally, the sequence and structure of peptide domains in otherwise conserved proteins. Nonetheless, the vulva is formed from the same three cells in both nematodes. I discuss redundancy as an evolutionary mechanism to explain developmental systems drift, a theory predicting conserved morphological structures to be generated by diverse molecular regulatory networks.}, } @article {pmid22817542, year = {2012}, author = {Chistyakov, VA and Denisenko, YV}, title = {Cellularity loss and Dilman's problem: an in silico study.}, journal = {Biochemistry. Biokhimiia}, volume = {77}, number = {7}, pages = {779-792}, doi = {10.1134/S0006297912070115}, pmid = {22817542}, issn = {1608-3040}, mesh = {*Aging/genetics ; *Apoptosis/genetics ; Biological Evolution ; Cell Survival/genetics ; *Computer Simulation ; Hormones/analysis/biosynthesis/*metabolism ; }, abstract = {We assume that prolonged trends of increasing concentration of hormones could be a consequence of deterioration of functioning of glands producing inhibitors of their synthesis. Such deterioration would result from loss of cellularity of the glands. Experiments in silico carried out using the model at http://www.winmobile.biz/monstr/ show that, in principle, the diversity of hormonal effects that accompany phenoptosis of multicellular organisms can be provided with a simple "software mechanism". This mechanism is based on the gradual loss of cellularity as a result of continuous run of apoptosis in some cells of the glands due to natural fluctuations in levels of intracellular inducers of apoptosis. The main practical sense of our work lies in the illustration of the fact that substances inhibiting cellularity loss can theoretically be effective suppressors of hormonal changes characteristic for aging.}, } @article {pmid22817532, year = {2012}, author = {Skulachev, VP}, title = {What is "phenoptosis" and how to fight it?.}, journal = {Biochemistry. Biokhimiia}, volume = {77}, number = {7}, pages = {689-706}, doi = {10.1134/S0006297912070012}, pmid = {22817532}, issn = {1608-3040}, mesh = {Aging/*genetics ; Animals ; Apoptosis/*genetics ; Biological Evolution ; Caloric Restriction ; *Death ; Genome/genetics ; Humans ; Mitochondria/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Phenoptosis is the death of an organism programmed by its genome. Numerous examples of phenoptosis are described in prokaryotes, unicellular eukaryotes, and all kingdoms of multicellular eukaryotes (animals, plants, and fungi). There are very demonstrative cases of acute phenoptosis when actuation of a specific biochemical or behavioral program results in immediate death. Rapid (taking days) senescence of semelparous plants is described as phenoptosis controlled by already known genes and mediated by toxic phytohormones like abscisic acid. In soya, the death signal is transmitted from beans to leaves via xylem, inducing leaf fall and death of the plant. Mutations in two genes of Arabidopsis thaliana, required for the flowering and subsequent formation of seeds, prevent senescence, strongly prolonging the lifespan of this small semelparous grass that becomes a big bush with woody stem, and initiate substitution of vegetative for sexual reproduction. The death of pacific salmon immediately after spawning is surely programmed. In this case, numerous typical traits of aging, including amyloid plaques in the brain, appear on the time scale of days. There are some indications that slow aging of higher animals and humans is also programmed, being the final step of ontogenesis. It is assumed that stepwise decline of many physiological functions during such aging increases pressure of natural selection on organisms stimulating in this way biological evolution. As a working hypothesis, the biochemical mechanism of slow aging is proposed. It is assumed that mitochondria-generated reactive oxygen species (ROS) is a tool to stimulate apoptosis, an effect decreasing with age the cell number (cellularity) of organs and tissues. A group of SkQ-type substances composed of plastoquinone and a penetrating cation were synthesized to target an antioxidant into mitochondria and to prevent the age-linked rise of the mitochondrial ROS level. Such targeting is due to the fact that mitochondria are the only cellular organelles that are negatively charged compared to the cytosol. SkQs are shown to strongly decrease concentration of ROS in mitochondria, prolong lifespan of fungi, invertebrates, fish, and mammals, and retard appearance of numerous traits of aging. Clinical trials of SkQ1 (plastoquinonyl decyltriphenylphosphonium) have been successfully completed so that the Ministry of Health of the Russian Federation recommends drops of very dilute (0.25 µM) solution of this antioxidant as a medicine to treat the syndrome of dry eye, which was previously considered an incurable disease developing with age. These drops are already available in drugstores. Thus, SkQ1 is the first mitochondria-targeted drug employed in medical practice.}, } @article {pmid22807664, year = {2012}, author = {Crombach, A and Wotton, KR and Cicin-Sain, D and Ashyraliyev, M and Jaeger, J}, title = {Efficient reverse-engineering of a developmental gene regulatory network.}, journal = {PLoS computational biology}, volume = {8}, number = {7}, pages = {e1002589}, pmid = {22807664}, issn = {1553-7358}, mesh = {Animals ; Computational Biology/*methods ; Computer Simulation ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/genetics/growth & development ; Gene Expression ; *Gene Regulatory Networks ; Genes, Insect ; Hybridization, Genetic ; Models, Genetic ; RNA, Messenger/genetics/metabolism ; }, abstract = {Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to discover whether there are rules or regularities governing development and evolution of complex multi-cellular organisms.}, } @article {pmid22806564, year = {2013}, author = {Zhao, J and Lendahl, U and Nistér, M}, title = {Regulation of mitochondrial dynamics: convergences and divergences between yeast and vertebrates.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {70}, number = {6}, pages = {951-976}, pmid = {22806564}, issn = {1420-9071}, mesh = {Animals ; *Biological Evolution ; Cell Line ; Dynamins ; GTP Phosphohydrolases/physiology ; Humans ; Microtubule-Associated Proteins/*metabolism/physiology ; Mitochondrial Dynamics/*physiology ; Mitochondrial Proteins/physiology ; *Models, Biological ; Saccharomyces cerevisiae/*physiology ; Species Specificity ; Vertebrates/*physiology ; }, abstract = {In eukaryotic cells, the shape of mitochondria can be tuned to various physiological conditions by a balance of fusion and fission processes termed mitochondrial dynamics. Mitochondrial dynamics controls not only the morphology but also the function of mitochondria, and therefore is crucial in many aspects of a cell's life. Consequently, dysfunction of mitochondrial dynamics has been implicated in a variety of human diseases including cancer. Several proteins important for mitochondrial fusion and fission have been discovered over the past decade. However, there is emerging evidence that there are as yet unidentified proteins important for these processes and that the fusion/fission machinery is not completely conserved between yeast and vertebrates. The recent characterization of several mammalian proteins important for the process that were not conserved in yeast, may indicate that the molecular mechanisms regulating and controlling the morphology and function of mitochondria are more elaborate and complex in vertebrates. This difference could possibly be a consequence of different needs in the different cell types of multicellular organisms. Here, we review recent advances in the field of mitochondrial dynamics. We highlight and discuss the mechanisms regulating recruitment of cytosolic Drp1 to the mitochondrial outer membrane by Fis1, Mff, and MIEF1 in mammals and the divergences in regulation of mitochondrial dynamics between yeast and vertebrates.}, } @article {pmid22802643, year = {2012}, author = {Lobikin, M and Wang, G and Xu, J and Hsieh, YW and Chuang, CF and Lemire, JM and Levin, M}, title = {Early, nonciliary role for microtubule proteins in left-right patterning is conserved across kingdoms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {31}, pages = {12586-12591}, pmid = {22802643}, issn = {1091-6490}, support = {R01 GM077425/GM/NIGMS NIH HHS/United States ; R01 HL095716/HL/NHLBI NIH HHS/United States ; HL095716/HL/NHLBI NIH HHS/United States ; R01-GM077425/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Blastomeres/cytology/*metabolism ; Body Patterning/*physiology ; Cell Division/*physiology ; HL-60 Cells ; Humans ; Microtubules/*metabolism ; Tubulin/*metabolism ; Xenopus Proteins/*metabolism ; Xenopus laevis ; }, abstract = {Many types of embryos' bodyplans exhibit consistently oriented laterality of the heart, viscera, and brain. Errors of left-right patterning present an important class of human birth defects, and considerable controversy exists about the nature and evolutionary conservation of the molecular mechanisms that allow embryos to reliably orient the left-right axis. Here we show that the same mutations in the cytoskeletal protein tubulin that alter asymmetry in plants also affect very early steps of left-right patterning in nematode and frog embryos, as well as chirality of human cells in culture. In the frog embryo, tubulin α and tubulin γ-associated proteins are required for the differential distribution of maternal proteins to the left or right blastomere at the first cell division. Our data reveal a remarkable molecular conservation of mechanisms initiating left-right asymmetry. The origin of laterality is cytoplasmic, ancient, and highly conserved across kingdoms, a fundamental feature of the cytoskeleton that underlies chirality in cells and multicellular organisms.}, } @article {pmid22796128, year = {2012}, author = {Gleason, EJ and Kramer, EM}, title = {Characterization of Aquilegia Polycomb Repressive Complex 2 homologs reveals absence of imprinting.}, journal = {Gene}, volume = {507}, number = {1}, pages = {54-60}, doi = {10.1016/j.gene.2012.07.004}, pmid = {22796128}, issn = {1879-0038}, mesh = {Aquilegia/*genetics ; Arabidopsis/genetics/metabolism ; Evolution, Molecular ; Gene Expression Regulation, Plant ; Genome, Plant ; *Genomic Imprinting ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Polycomb-Group Proteins ; Repressor Proteins/*genetics ; }, abstract = {Epigenetic regulation is important for maintaining gene expression patterns in multicellular organisms. The Polycomb Group (PcG) proteins form several complexes with important and deeply conserved epigenetic functions in both the plant and animal kingdoms. The plant Polycomb Repressive Complex 2 (PRC2) contains four core proteins, Enhancer of Zeste (E(z)), Suppressor of Zeste 12 (Su(z)12), Extra Sex Combs (ESC), and Multicopy Suppressor of IRA 1 (MSI1), and functions in many developmental transitions. In some plant species, including rice and Arabidopsis, duplications in the core PRC2 proteins allow the formation of PRC2s with distinct developmental functions. In addition, members of the plant specific VEL PHD family have been shown to associate with the PRC2 complex in Arabidopsis and may play a role in targeting the PRC2 to specific loci. Here we examine the evolution and expression of the PRC2 and VEL PHD families in Aquilegia, a member of the lower eudicot order Ranunculales and an emerging model for the investigation of plant ecology, evolution and developmental genetics. We find that Aquilegia has a relatively simple PRC2 with only one homolog of Su(z)12, ESC and MSI1 and two ancient copies of E(z), AqSWN and AqCLF. Aquilegia has four members of the VEL PHD family, three of which appear to be closely related to Arabidopsis proteins known to associate with the PRC2. The PRC2 and VEL PHD family proteins are expressed at a relatively constant level throughout Aquilegia vulgaris development, with the VEL PHD family and MSI1 expressed at higher levels during and after vernalization and in the inflorescence. Both AqSWN and AqCLF are expressed in Aquilegia endosperm but neither copy is imprinted.}, } @article {pmid22792236, year = {2012}, author = {Hosp, J and Sagane, Y and Danks, G and Thompson, EM}, title = {The evolving proteome of a complex extracellular matrix, the Oikopleura house.}, journal = {PloS one}, volume = {7}, number = {7}, pages = {e40172}, pmid = {22792236}, issn = {1932-6203}, mesh = {Animals ; Epithelium/metabolism ; Extracellular Matrix/*metabolism ; Female ; Gene Order ; Genome ; Glycoproteins/genetics/metabolism ; Heparan Sulfate Proteoglycans/metabolism ; Immunity, Innate/genetics ; Male ; Phylogeny ; Protein Transport ; Proteome/*metabolism ; Urochordata/genetics/immunology/*metabolism ; }, abstract = {Extracellular matrices regulate biological processes at the level of cells, tissues, and in some cases, entire multicellular organisms. The subphylum Urochordata exemplifies the latter case, where animals are partially or completely enclosed in "houses" or "tunics". Despite this common strategy, we show that the house proteome of the appendicularian, Oikopleura, has very little in common with the proteome of the sister class, ascidian, Ciona. Of 80 identified house proteins (oikosins), ∼half lack domain modules or similarity to known proteins, suggesting de novo appearance in appendicularians. Gene duplication has been important in generating almost 1/3 of the current oikosin complement, with serial duplications up to 8 paralogs in one family. Expression pattern analyses revealed that individual oikosins are produced from specific fields of cells within the secretory epithelium, but in some cases, migrate up to at least 20 cell diameters in extracellular space to combine in defined house structures. Interestingly, peroxidasin and secretory phospholipase A(2) domains, implicated in innate immune defence are secreted from the anlage associated with the food-concentrating filter, suggesting that this extra-organismal structure may play, in part, such a role in Oikopleura. We also show that sulfation of proteoglycans is required for the hydration and inflation of pre-house rudiments into functional houses. Though correct proportioning in the production of oikosins would seem important in repetitive assembly of the complex house structure, the genomic organization of oikosin loci appears incompatible with common enhancers or locus control regions exerting such a coordinate regulatory role. Thus, though all tunicates employ extracellular matrices based on a cellulose scaffold as a defining feature of the subphylum, they have evolved radically different protein compositions associated with this common underlying structural theme.}, } @article {pmid22768154, year = {2012}, author = {Lizier, NF and Kerkis, A and Gomes, CM and Hebling, J and Oliveira, CF and Caplan, AI and Kerkis, I}, title = {Scaling-up of dental pulp stem cells isolated from multiple niches.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e39885}, pmid = {22768154}, issn = {1932-6203}, mesh = {Biomarkers/metabolism ; Bromodeoxyuridine/metabolism ; Cell Count ; Cell Culture Techniques ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Cell Separation/*methods ; Cells, Cultured ; Child ; Chondrogenesis/drug effects ; Culture Media/pharmacology ; Dental Pulp/*cytology ; Embryonic Stem Cells/cytology/drug effects/metabolism ; Gene Expression Regulation/drug effects ; Humans ; Immunophenotyping ; Mesenchymal Stem Cells/cytology/drug effects/metabolism ; Muscle Development/drug effects ; *Stem Cell Niche/drug effects ; Stem Cells/*cytology/drug effects/metabolism/ultrastructure ; Time Factors ; }, abstract = {Dental pulp (DP) can be extracted from child's primary teeth (deciduous), whose loss occurs spontaneously by about 5 to 12 years. Thus, DP presents an easy accessible source of stem cells without ethical concerns. Substantial quantities of stem cells of an excellent quality and at early (2-5) passages are necessary for clinical use, which currently is a problem for use of adult stem cells. Herein, DPs were cultured generating stem cells at least during six months through multiple mechanical transfers into a new culture dish every 3-4 days. We compared stem cells isolated from the same DP before (early population, EP) and six months after several mechanical transfers (late population, LP). No changes, in both EP and LP, were observed in morphology, expression of stem cells markers (nestin, vimentin, fibronectin, SH2, SH3 and Oct3/4), chondrogenic and myogenic differentiation potential, even after cryopreservation. Six hours after DP extraction and in vitro plating, rare 5-bromo-2'-deoxyuridine (BrdU) positive cells were observed in pulp central part. After 72 hours, BrdU positive cells increased in number and were found in DP periphery, thus originating a multicellular population of stem cells of high purity. Multiple stem cell niches were identified in different zones of DP, because abundant expression of nestin, vimentin and Oct3/4 proteins was observed, while STRO-1 protein localization was restricted to perivascular niche. Our finding is of importance for the future of stem cell therapies, providing scaling-up of stem cells at early passages with minimum risk of losing their "stemness".}, } @article {pmid22765842, year = {2012}, author = {Forte, E and Miraldi, F and Chimenti, I and Angelini, F and Zeuner, A and Giacomello, A and Mercola, M and Messina, E}, title = {TGFβ-dependent epithelial-to-mesenchymal transition is required to generate cardiospheres from human adult heart biopsies.}, journal = {Stem cells and development}, volume = {21}, number = {17}, pages = {3081-3090}, pmid = {22765842}, issn = {1557-8534}, support = {R37 HL059502/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Benzamides/pharmacology ; Biomarkers/metabolism ; Biopsy ; Cell Differentiation ; Cells, Cultured ; Dioxoles/pharmacology ; *Epithelial-Mesenchymal Transition ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Myocardial Ischemia/metabolism/pathology ; Myocardium/metabolism/*pathology ; Myocytes, Cardiac/*cytology/metabolism ; Receptor, Notch1/genetics/metabolism ; Receptors, Transforming Growth Factor beta/antagonists & inhibitors ; *Regeneration ; Snail Family Transcription Factors ; Stem Cells/*cytology/metabolism ; Transcription Factors/genetics/metabolism ; Transforming Growth Factor beta/*metabolism/pharmacology ; }, abstract = {Autologous cardiac progenitor cells (CPCs) isolated as cardiospheres (CSps) represent a promising candidate for cardiac regenerative therapy. A better understanding of the origin and mechanisms underlying human CSps formation and maturation is undoubtedly required to enhance their cardiomyogenic potential. Epithelial-to-mesenchymal transition (EMT) is a key morphogenetic process that is implicated in the acquisition of stem cell-like properties in different adult tissues, and it is activated in the epicardium after ischemic injury to the heart. We investigated whether EMT is involved in the formation and differentiation of human CSps, revealing that an up-regulation of the expression of EMT-related genes accompanies CSps formation that is relative to primary explant-derived cells and CSp-derived cells grown in a monolayer. EMT and CSps formation is enhanced in the presence of transforming growth factor β1 (TGFβ1) and drastically blocked by the type I TGFβ-receptor inhibitor SB431452, indicating that TGFβ-dependent EMT is essential for the formation of these niche-like 3D-multicellular clusters. Since TGFβ is activated in the myocardium in response to injury, our data suggest that CSps formation mimics an adaptive mechanism that could potentially be enhanced to increase in vivo or ex vivo regenerative potential of adult CPCs.}, } @article {pmid22726356, year = {2012}, author = {Rehfeld, JF}, title = {Beginnings: a reflection on the history of gastrointestinal endocrinology.}, journal = {Regulatory peptides}, volume = {177 Suppl}, number = {}, pages = {S1-5}, doi = {10.1016/j.regpep.2012.05.087}, pmid = {22726356}, issn = {1873-1686}, mesh = {Animals ; Cell Membrane/chemistry ; Drug Therapy/methods ; Endocrine Glands/chemistry/metabolism ; Endocrinology/history ; Gastrointestinal Hormones/*chemistry/classification/genetics/metabolism ; Gastrointestinal Tract/chemistry/*metabolism ; Genes, Regulator ; History, 20th Century ; History, 21st Century ; Humans ; Neuroendocrine Tumors/chemistry/therapy ; Peptide Hormones/*chemistry/classification/genetics/metabolism ; Phylogeny ; Radioimmunoassay ; }, abstract = {The gut is the largest endocrine organ in the body. Gut hormones share some characteristics: Their structure groups hormones into families, each of which originate from a single gene. A hormone gene is often expressed in multiple peptides due to tandem genes, alternative splicing or differentiated posttranslational processing. By these mechanisms, more than 100 different hormonally active peptides are produced in the gastrointestinal tract. In addition, gut hormones are widely expressed outside the gut. The different cell types often express different products of the same gene and release the peptides in different ways. Consequently, the same peptide may act as a hormone, a local growth factor, or a neurotransmitter. This new biology suggests that gastrointestinal hormones should be conceived as intercellular messengers of major general impact. The following short review is a vignette on steps in the history of gastrointestinal endocrinology from classic studies of digestive juice secretion over peptide chemistry, immunochemistry, and molecular genetics to modern receptor pharmacology and drug development. From shadowy beginnings, gastrointestinal endocrinology has emerged as a central discipline in the understanding of multicellular life and its diseases.}, } @article {pmid22763458, year = {2012}, author = {Steinmetz, PR and Kraus, JE and Larroux, C and Hammel, JU and Amon-Hassenzahl, A and Houliston, E and Wörheide, G and Nickel, M and Degnan, BM and Technau, U}, title = {Independent evolution of striated muscles in cnidarians and bilaterians.}, journal = {Nature}, volume = {487}, number = {7406}, pages = {231-234}, pmid = {22763458}, issn = {1476-4687}, support = {P 21108/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; *Biological Evolution ; Cnidaria/*anatomy & histology/genetics/metabolism ; Gene Duplication ; Gene Expression Regulation ; Muscle, Striated/metabolism/*physiology ; Myosin Heavy Chains/genetics/metabolism ; Phylogeny ; }, abstract = {Striated muscles are present in bilaterian animals (for example, vertebrates, insects and annelids) and some non-bilaterian eumetazoans (that is, cnidarians and ctenophores). The considerable ultrastructural similarity of striated muscles between these animal groups is thought to reflect a common evolutionary origin. Here we show that a muscle protein core set, including a type II myosin heavy chain (MyHC) motor protein characteristic of striated muscles in vertebrates, was already present in unicellular organisms before the origin of multicellular animals. Furthermore, 'striated muscle' and 'non-muscle' myhc orthologues are expressed differentially in two sponges, compatible with a functional diversification before the origin of true muscles and the subsequent use of striated muscle MyHC in fast-contracting smooth and striated muscle. Cnidarians and ctenophores possess striated muscle myhc orthologues but lack crucial components of bilaterian striated muscles, such as genes that code for titin and the troponin complex, suggesting the convergent evolution of striated muscles. Consistently, jellyfish orthologues of a shared set of bilaterian Z-disc proteins are not associated with striated muscles, but are instead expressed elsewhere or ubiquitously. The independent evolution of eumetazoan striated muscles through the addition of new proteins to a pre-existing, ancestral contractile apparatus may serve as a model for the evolution of complex animal cell types.}, } @article {pmid22751134, year = {2013}, author = {DeGregori, J}, title = {Challenging the axiom: does the occurrence of oncogenic mutations truly limit cancer development with age?.}, journal = {Oncogene}, volume = {32}, number = {15}, pages = {1869-1875}, pmid = {22751134}, issn = {1476-5594}, support = {R01 CA157850/CA/NCI NIH HHS/United States ; R01CA157850/CA/NCI NIH HHS/United States ; }, mesh = {Age Factors ; Aging/*genetics ; Cell Transformation, Neoplastic/*genetics ; DNA Repair/genetics ; Humans ; Models, Biological ; Mutation ; *Mutation Rate ; Neoplasms/*genetics ; Phenotype ; }, abstract = {A widely accepted paradigm in cancer research holds that the development of cancers is rate limited by the occurrence of oncogenic mutations. In particular, the exponential rise in the incidence of most cancers with age is thought to reflect the time required for cells to accumulate the multiple oncogenic mutations needed to confer the cancer phenotype. Here I will argue against the axiom that the occurrence of oncogenic mutations limits cancer incidence with age, based on several observations, including that the rate of mutation accumulation is maximal during ontogeny, oncogenic mutations are frequently detected in normal tissues, the evolution of complex multicellularity was not accompanied by reductions in mutation rates, and that many oncogenic mutations have been shown to impair stem cell activity. Moreover, although evidence that has been used to support the current paradigm includes increased cancer incidence in individuals with inherited DNA repair deficiencies or exposed to mutagens, the pleotropic effects of these contexts could enhance tumorigenesis at multiple levels. I will further argue that age-dependent alteration of selection for oncogenic mutations provides a more plausible explanation for increased cancer incidence in the elderly. Although oncogenic mutations are clearly required for cancer evolution, together these observations counter the common view that age dependence of cancers is largely explained by the time required to accumulate sufficient oncogenic mutations.}, } @article {pmid22749958, year = {2012}, author = {Morris, DJ}, title = {A new model for myxosporean (Myxozoa) development explains the endogenous budding phenomenon, the nature of cell within cell life stages and evolution of parasitism from a cnidarian ancestor.}, journal = {International journal for parasitology}, volume = {42}, number = {9}, pages = {829-840}, doi = {10.1016/j.ijpara.2012.06.001}, pmid = {22749958}, issn = {1879-0135}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; *Models, Biological ; Myxozoa/*cytology/genetics/*growth & development ; Spores, Protozoan/physiology ; }, abstract = {The phylum Myxozoa is composed of endoparasitic species that have predominately been recorded within aquatic vertebrates. The simple body form of a trophic cell containing other cells within it, as observed within these hosts, has provided few clues to relationships with other organisms. In addition, the placement of the group using molecular phylogenies has proved very difficult, although the majority of analyses now suggest that they are cnidarians. There have been relatively few studies of myxozoan stages within invertebrate hosts, even though these exhibit multicellular and sexual stages that may provide clues to myxozoan evolution. Therefore an ultrastructural examination of a myxozoan infection of a freshwater oligochaete was conducted, to reassess and formulate a model for myxozoan development in these hosts. This deemed that meiosis occurs within the oligochaete, but that fertilisation is not immediate. Rather, the resultant haploid germ cell (oocyte) is engulfed by a diploid sporogonic cell (nurse cell) to form a sporoplasm. It is this sporoplasm that infects the fish, resulting in the multicellular stages observed. Fertilisation occurs after the parasites leave the fish and enter the oligochaete host. The nurse cell/oocyte model explains previously conflicting evidence in the literature regarding myxosporean biology, and aligns phenomena considered distinctive to the Myxozoa, such as endogenous budding and cell within cell development, with processes recorded in cnidarians. Finally, the evolutionary origin of the Myxozoa as cnidarian parasites of ova is hypothesised.}, } @article {pmid22734652, year = {2012}, author = {Alvarez-Venegas, R and Avramova, Z}, title = {Evolution of the PWWP-domain encoding genes in the plant and animal lineages.}, journal = {BMC evolutionary biology}, volume = {12}, number = {}, pages = {101}, pmid = {22734652}, issn = {1471-2148}, mesh = {Animals ; Arabidopsis/genetics ; Chlorophyta/genetics ; Humans ; Methyltransferases/*genetics ; Nuclear Proteins/chemistry/*genetics ; Plants/*genetics ; *Protein Structure, Tertiary ; Sea Anemones/*genetics ; }, abstract = {BACKGROUND: Conserved domains are recognized as the building blocks of eukaryotic proteins. Domains showing a tendency to occur in diverse combinations ('promiscuous' domains) are involved in versatile architectures in proteins with different functions. Current models, based on global-level analyses of domain combinations in multiple genomes, have suggested that the propensity of some domains to associate with other domains in high-level architectures increases with organismal complexity. Alternative models using domain-based phylogenetic trees propose that domains have become promiscuous independently in different lineages through convergent evolution and are, thus, random with no functional or structural preferences. Here we test whether complex protein architectures have occurred by accretion from simpler systems and whether the appearance of multidomain combinations parallels organismal complexity. As a model, we analyze the modular evolution of the PWWP domain and ask whether its appearance in combinations with other domains into multidomain architectures is linked with the occurrence of more complex life-forms. Whether high-level combinations of domains are conserved and transmitted as stable units (cassettes) through evolution is examined in the genomes of plant or metazoan species selected for their established position in the evolution of the respective lineages.

RESULTS: Using the domain-tree approach, we analyze the evolutionary origins and distribution patterns of the promiscuous PWWP domain to understand the principles of its modular evolution and its existence in combination with other domains in higher-level protein architectures. We found that as a single module the PWWP domain occurs only in proteins with a limited, mainly, species-specific distribution. Earlier, it was suggested that domain promiscuity is a fast-changing (volatile) feature shaped by natural selection and that only a few domains retain their promiscuity status throughout evolution. In contrast, our data show that most of the multidomain PWWP combinations in extant multicellular organisms (humans or land plants) are present in their unicellular ancestral relatives suggesting they have been transmitted through evolution as conserved linear arrangements ('cassettes'). Among the most interesting biologically relevant results is the finding that the genes of the two plant Trithorax family subgroups (ATX1/2 and ATX3/4/5) have different phylogenetic origins. The two subgroups occur together in the earliest land plants Physcomitrella patens and Selaginella moellendorffii.

CONCLUSION: Gain/loss of a single PWWP domain is observed throughout evolution reflecting dynamic lineage- or species-specific events. In contrast, higher-level protein architectures involving the PWWP domain have survived as stable arrangements driven by evolutionary descent. The association of PWWP domains with the DNA methyltransferases in O. tauri and in the metazoan lineage seems to have occurred independently consistent with convergent evolution. Our results do not support models wherein more complex protein architectures involving the PWWP domain occur with the appearance of more evolutionarily advanced life forms.}, } @article {pmid22730024, year = {2012}, author = {Jones, VA and Dolan, L}, title = {The evolution of root hairs and rhizoids.}, journal = {Annals of botany}, volume = {110}, number = {2}, pages = {205-212}, pmid = {22730024}, issn = {1095-8290}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Biological Evolution ; Bryophyta/genetics/growth & development ; Cell Differentiation/genetics ; Germ Cells, Plant/growth & development ; Phylogeny ; Plant Roots/cytology/*genetics/*growth & development ; Plants/*genetics ; Rhizome/cytology/*genetics/*growth & development ; }, abstract = {BACKGROUND: Almost all land plants develop tip-growing filamentous cells at the interface between the plant and substrate (the soil). Root hairs form on the surface of roots of sporophytes (the multicellular diploid phase of the life cycle) in vascular plants. Rhizoids develop on the free-living gametophytes of vascular and non-vascular plants and on both gametophytes and sporophytes of the extinct rhyniophytes. Extant lycophytes (clubmosses and quillworts) and monilophytes (ferns and horsetails) develop both free-living gametophytes and free-living sporophytes. These gametophytes and sporophytes grow in close contact with the soil and develop rhizoids and root hairs, respectively.

SCOPE: Here we review the development and function of rhizoids and root hairs in extant groups of land plants. Root hairs are important for the uptake of nutrients with limited mobility in the soil such as phosphate. Rhizoids have a variety of functions including water transport and adhesion to surfaces in some mosses and liverworts.

CONCLUSIONS: A similar gene regulatory network controls the development of rhizoids in moss gametophytes and root hairs on the roots of vascular plant sporophytes. It is likely that this gene regulatory network first operated in the gametophyte of the earliest land plants. We propose that later it functioned in sporophytes as the diploid phase evolved a free-living habit and developed an interface with the soil. This transference of gene function from gametophyte to sporophyte could provide a mechanism that, at least in part, explains the increase in morphological diversity of sporophytes that occurred during the radiation of land plants in the Devonian Period.}, } @article {pmid22717455, year = {2012}, author = {Joachim, J and Wirth, M and McKnight, NC and Tooze, SA}, title = {Coiling up with SCOC and WAC: two new regulators of starvation-induced autophagy.}, journal = {Autophagy}, volume = {8}, number = {9}, pages = {1397-1400}, doi = {10.4161/auto.21043}, pmid = {22717455}, issn = {1554-8635}, support = {//Cancer Research UK/United Kingdom ; }, mesh = {Adaptor Proteins, Signal Transducing/*metabolism ; Animals ; *Autophagy ; Caenorhabditis elegans/metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Membrane Proteins/*metabolism ; Models, Biological ; Phagosomes/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis ; *Signal Transduction ; Starvation/*pathology ; Ubiquitination ; }, abstract = {Autophagy is a conserved and highly regulated catabolic pathway, transferring cytoplasmic components in autophagosomes to lysosomes for degradation and providing amino acids during starvation. In multicellular organisms autophagy plays an important role for tissue homeostasis, and deregulation of autophagy has been implicated in a broad range of diseases, including cancer and neurodegenerative disorders. In mammals, many aspects of autophagy still need to be fully elucidated: what is the exact hierarchy and relationship between ATG proteins and other factors that lead to the formation and expansion of phagophores? Where does the membrane source for autophagosome formation originate? Which signaling events trigger amino acid starvation-induced autophagy? How are the activities of ULK1/2 and the class III PtdIns3K regulated and linked to each other? To develop therapeutic strategies to manipulate autophagy in human disease, a comprehensive understanding of the molecular protein machinery mediating and regulating autophagy is required.}, } @article {pmid22709976, year = {2012}, author = {Joachimczak, M and Wróbel, B}, title = {Evolution of robustness to damage in artificial 3-dimensional development.}, journal = {Bio Systems}, volume = {109}, number = {3}, pages = {498-505}, doi = {10.1016/j.biosystems.2012.05.014}, pmid = {22709976}, issn = {1872-8324}, mesh = {*Algorithms ; *Biological Evolution ; Computer Simulation ; *Embryonic Development ; Gene Regulatory Networks/*genetics ; *Models, Biological ; Morphogenesis/*physiology ; *Software ; }, abstract = {GReaNs is an Artificial Life platform we have built to investigate the general principles that guide evolution of multicellular development and evolution of artificial gene regulatory networks. The embryos develop in GReaNs in a continuous 3-dimensional (3D) space with simple physics. The developmental trajectories are indirectly encoded in linear genomes. The genomes are not limited in size and determine the topology of gene regulatory networks that are not limited in the number of nodes. The expression of the genes is continuous and can be modified by adding environmental noise. In this paper we evolved development of structures with a specific shape (an ellipsoid) and asymmetrical pattering (a 3D pattern inspired by the French flag problem), and investigated emergence of the robustness to damage in development and the emergence of the robustness to noise. Our results indicate that both types of robustness are related, and that including noise during evolution promotes higher robustness to damage. Interestingly, we have observed that some evolved gene regulatory networks rely on noise for proper behaviour.}, } @article {pmid22702725, year = {2012}, author = {Xue, B and Dunker, AK and Uversky, VN}, title = {Orderly order in protein intrinsic disorder distribution: disorder in 3500 proteomes from viruses and the three domains of life.}, journal = {Journal of biomolecular structure & dynamics}, volume = {30}, number = {2}, pages = {137-149}, doi = {10.1080/07391102.2012.675145}, pmid = {22702725}, issn = {1538-0254}, mesh = {Animals ; Binding Sites ; Computational Biology ; Eukaryota/genetics/metabolism ; Evolution, Molecular ; Humans ; Protein Conformation ; Proteins/*chemistry/metabolism ; Proteome/*chemistry ; Viruses/genetics/metabolism ; }, abstract = {Intrinsically disordered proteins and intrinsically disordered protein regions are highly abundant in nature. However, the quantitative and qualitative measures of protein intrinsic disorder in species with known genomes are still not available. Furthermore, although the correlation between high fraction of disordered residues and advanced species has been reported, the details of this correlation and the connection between the disorder content and proteome complexity have not been reported as of yet. To fill this gap, we analysed entire proteomes of 3484 species from three domains of life (archaea, bacteria and eukaryotes) and from viruses. Our analysis revealed that the evolution process is characterized by distinctive patterns of changes in the protein intrinsic disorder content. We are showing here that viruses are characterized by the widest spread of the proteome disorder content (the percentage of disordered residues ranges from 7.3% in human coronavirus NL63 to 77.3% in Avian carcinoma virus). For several organisms, a clear correlation is seen between their disorder contents and habitats. In multicellular eukaryotes, there is a weak correlation between the complexity of an organism (evaluated as a number of different cell types) and its overall disorder content. For both the prokaryotes and eukaryotes, the disorder content is generally independent of the proteome size. However, disorder shows a sharp increase associated with the transition from prokaryotic to eukaryotic cells. This suggests that the increased disorder content in eukaryotic proteomes might be used by nature to deal with the increased cell complexity due to the appearance of the various cellular compartments.}, } @article {pmid22698377, year = {2012}, author = {Tossi, V and Cassia, R and Bruzzone, S and Zocchi, E and Lamattina, L}, title = {ABA says NO to UV-B: a universal response?.}, journal = {Trends in plant science}, volume = {17}, number = {9}, pages = {510-517}, doi = {10.1016/j.tplants.2012.05.007}, pmid = {22698377}, issn = {1878-4372}, mesh = {Abscisic Acid/*physiology/radiation effects ; Amino Acid Sequence ; Animals ; Calcium/physiology ; Humans ; Models, Biological ; Molecular Sequence Data ; Nitric Oxide/*physiology ; Phylogeny ; Plants/metabolism ; Sequence Alignment ; Signal Transduction/*drug effects/radiation effects ; Stress, Physiological/*drug effects/physiology ; *Ultraviolet Rays ; }, abstract = {Abscisic acid (ABA) signaling pathways have been widely characterized in plants, whereas the function of ABA in animals is less well understood. However, recent advances show ABA production by a wide range of lower animals and higher mammals. This enables a new evaluation of ABA signaling pathways in different organisms in response to common environmental stress, such as ultraviolet (UV)-B. In this opinion article, we propose that the induction of common signaling components, such as ABA, nitric oxide (NO) and Ca(2+), in plant and animal cells in response to high doses of UV-B, suggests that the evolution of a general mechanism activated by UV-B is conserved in divergent multicellular organisms challenged by a changing common environment.}, } @article {pmid22690978, year = {2012}, author = {Ni, T and Yue, J and Sun, G and Zou, Y and Wen, J and Huang, J}, title = {Ancient gene transfer from algae to animals: mechanisms and evolutionary significance.}, journal = {BMC evolutionary biology}, volume = {12}, number = {}, pages = {83}, pmid = {22690978}, issn = {1471-2148}, mesh = {Animals ; Choanoflagellata/*genetics ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; Multigene Family ; Phylogeny ; Plants/*genetics ; Plastids/genetics ; }, abstract = {BACKGROUND: Horizontal gene transfer (HGT) is traditionally considered to be rare in multicellular eukaryotes such as animals. Recently, many genes of miscellaneous algal origins were discovered in choanoflagellates. Considering that choanoflagellates are the existing closest relatives of animals, we speculated that ancient HGT might have occurred in the unicellular ancestor of animals and affected the long-term evolution of animals.

RESULTS: Through genome screening, phylogenetic and domain analyses, we identified 14 gene families, including 92 genes, in the tunicate Ciona intestinalis that are likely derived from miscellaneous photosynthetic eukaryotes. Almost all of these gene families are distributed in diverse animals, suggesting that they were mostly acquired by the common ancestor of animals. Their miscellaneous origins also suggest that these genes are not derived from a particular algal endosymbiont. In addition, most genes identified in our analyses are functionally related to molecule transport, cellular regulation and methylation signaling, suggesting that the acquisition of these genes might have facilitated the intercellular communication in the ancestral animal.

CONCLUSIONS: Our findings provide additional evidence that algal genes in aplastidic eukaryotes are not exclusively derived from historical plastids and thus important for interpreting the evolution of eukaryotic photosynthesis. Most importantly, our data represent the first evidence that more anciently acquired genes might exist in animals and that ancient HGT events have played an important role in animal evolution.}, } @article {pmid22679768, year = {2012}, author = {Savost'ianov, GA}, title = {[The origin of elementary units of multicellularity and development of a spatial organization of cell layers].}, journal = {Izvestiia Akademii nauk. Seriia biologicheskaia}, volume = {}, number = {2}, pages = {164-174}, pmid = {22679768}, issn = {1026-3470}, mesh = {Animals ; Cells/*cytology/ultrastructure ; Computer Simulation ; Epithelium/embryology/ultrastructure ; Humans ; *Models, Biological ; *Morphogenesis ; }, abstract = {The concept of the elementary unit of multicellularity, the histion, which also serves as a morphofunctional unit of cell layers, is introduced. Histions are cell groups formed as a result of division of labor between cells. Cell layers are regarded as regular cell networks (lattices) formed through polymerization of histions. The theory constructed based on this concept allows the composition and structure of a multitude of histions to be calculated; their development to be quantified; and families of topological and geometrical models for the histoarchitecture of cell layers to be constructed, visualized with computer programs, and experimentally verified. In addition, this model can predict previously unknown topological variants of the histoarchitecture of epithelial tissues, as well as their presence in normal development and pathology.}, } @article {pmid22674065, year = {2012}, author = {Harris, TJ}, title = {An introduction to adherens junctions: from molecular mechanisms to tissue development and disease.}, journal = {Sub-cellular biochemistry}, volume = {60}, number = {}, pages = {1-5}, doi = {10.1007/978-94-007-4186-7_1}, pmid = {22674065}, issn = {0306-0225}, mesh = {Adherens Junctions/*physiology ; Animals ; Cadherins/*metabolism ; Catenins/*metabolism ; *Disease ; Humans ; Morphogenesis ; }, abstract = {Adherens junctions (AJs) are fundamental for the development of animal tissues and organs. The core complex is formed from transmembrane cell-cell adhesion molecules, cadherins, and adaptor molecules, the catenins, that link to cytoskeletal and regulatory networks within the cell. This complex can be considered over a wide range of biological organization, from atoms to molecules, protein complexes, molecular networks, cells, tissues, and overall animal development. AJs have also been an integral part of animal evolution, and play central roles in cancer development and pathogen infection. This book addresses major questions encompassing these aspects of AJ biology. How did AJs evolve? How do the cadherins and catenins interact to assemble AJs and mediate adhesion? How do AJs interface with other cellular machinery to couple adhesion with the whole cell? How do AJs affect cell behaviour and multicellular development? How can abnormal AJ activity lead to disease?}, } @article {pmid22664124, year = {2012}, author = {Wang, X and Schröder, HC and Wiens, M and Schloßmacher, U and Müller, WE}, title = {Biosilica: Molecular Biology, Biochemistry and Function in Demosponges as well as its Applied Aspects for Tissue Engineering.}, journal = {Advances in marine biology}, volume = {62}, number = {}, pages = {231-271}, doi = {10.1016/B978-0-12-394283-8.00005-9}, pmid = {22664124}, issn = {0065-2881}, mesh = {Animals ; Cathepsins ; Models, Molecular ; Molecular Biology ; Phylogeny ; Porifera ; *Silicon Dioxide ; *Tissue Engineering ; }, abstract = {Biomineralization, biosilicification in particular (i.e. the formation of biogenic silica, SiO(2)), has become an exciting source of inspiration for the development of novel bionic approaches following 'nature as model'. Siliceous sponges are unique among silica-forming organisms in their ability to catalyze silica formation using a specific enzyme termed silicatein. In this study, we review the present state of knowledge on silicatein-mediated 'biosilica' formation in marine demosponges, the involvement of further molecules in silica metabolism and their potential applications in nano-biotechnology and bio-medicine. While most forms of multicellular life have developed a calcium-based skeleton, a few specialized organisms complement their body plan with silica. Only sponges (phylum Porifera) are able to polymerize silica enzymatically mediated in order to generate massive siliceous skeletal elements (spicules) during a unique reaction, at ambient temperature and pressure. During this biomineralization process (i.e. biosilicification), hydrated, amorphous silica is deposited within highly specialized sponge cells, ultimately resulting in structures that range in size from micrometres to metres. This peculiar phenomenon has been comprehensively studied in recent years, and in several approaches, the molecular background was explored to create tools that might be employed for novel bioinspired biotechnological and biomedical applications. Thus, it was discovered that spiculogenesis is mediated by the enzyme silicatein and starts intracellularly. The resulting silica nanoparticles fuse and subsequently form concentric lamellar layers around a central protein filament, consisting of silicatein and the scaffold protein silintaphin-1. Once the growing spicule is extruded into the extracellular space, it obtains final size and shape. Again, this process is mediated by silicatein and silintaphin-1/silintaphin-1, in combination with other molecules such as galectin and collagen. The molecular toolbox generated so far allows the fabrication of novel micro- and nano-structured composites, contributing to the economical and sustainable synthesis of biomaterials with unique characteristics. In this context, first bioinspired approaches implement recombinant silicatein and silintaphin-1 for applications in the field of biomedicine (biosilica-mediated regeneration of tooth and bone defects) with promising results.}, } @article {pmid22662159, year = {2012}, author = {Coppin, E and Berteaux-Lecellier, V and Bidard, F and Brun, S and Ruprich-Robert, G and Espagne, E and Aït-Benkhali, J and Goarin, A and Nesseir, A and Planamente, S and Debuchy, R and Silar, P}, title = {Systematic deletion of homeobox genes in Podospora anserina uncovers their roles in shaping the fruiting body.}, journal = {PloS one}, volume = {7}, number = {5}, pages = {e37488}, pmid = {22662159}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Evolution, Molecular ; Fertility/genetics ; Fruiting Bodies, Fungal/*genetics ; *Gene Deletion ; *Genes, Homeobox ; Genotype ; Molecular Sequence Data ; Mutation ; Phenotype ; Podospora/*genetics/metabolism ; Sequence Alignment ; Transcription Factors/chemistry/genetics/metabolism ; }, abstract = {Higher fungi, which comprise ascomycetes and basidiomycetes, play major roles in the biosphere. Their evolutionary success may be due to the extended dikaryotic stage of their life cycle, which is the basis for their scientific name: the Dikarya. Dikaryosis is maintained by similar structures, the clamp in basidiomycetes and the crozier in ascomycetes. Homeodomain transcription factors are required for clamp formation in all basidiomycetes studied. We identified all the homeobox genes in the filamentous ascomycete fungus Podospora anserina and constructed deletion mutants for each of these genes and for a number of gene combinations. Croziers developed normally in these mutants, including those with up to six deleted homeogenes. However, some mutants had defects in maturation of the fruiting body, an effect that could be rescued by providing wild-type maternal hyphae. Analysis of mutants deficient in multiple homeogenes revealed interactions between the genes, suggesting that they operate as a complex network. Similar to their role in animals and plants, homeodomain transcription factors in ascomycetes are involved in shaping multicellular structures.}, } @article {pmid22647940, year = {2012}, author = {Crossin, KL}, title = {Oxygen levels and the regulation of cell adhesion in the nervous system: a control point for morphogenesis in development, disease and evolution?.}, journal = {Cell adhesion & migration}, volume = {6}, number = {1}, pages = {49-58}, pmid = {22647940}, issn = {1933-6926}, mesh = {Animals ; Atmosphere ; Brain Ischemia ; Cell Adhesion ; Cell Proliferation ; *Evolution, Molecular ; Hypoxia, Brain/metabolism/pathology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; *Morphogenesis ; Nervous System/cytology/*metabolism ; Neural Cell Adhesion Molecules/metabolism ; Neural Stem Cells/cytology/metabolism ; Neurogenesis ; Oxygen/*metabolism ; Symbiosis ; Wnt Signaling Pathway ; }, abstract = {In this article, I discuss the hallmarks of hypoxia in vitro and in vivo and review work showing that many types of stem cell proliferate more robustly in lowered oxygen. I then discuss recent studies showing that alterations in the levels and the types of cell and substrate adhesion molecules are a notable response to reduced O(2) levels in both cultured primary neural stem cells and brain tissues in response to hypoxia in vivo. The ability of O(2) levels to regulate adhesion molecule expression is linked to the Wnt signaling pathway, which can control and be controlled by adhesion events. The ability of O(2) levels to influence cell adhesion also has far-reaching implications for development, ischemic trauma and neural regeneration, as well as for cancer and other diseases. Finally I discuss the possibility that the fluctuations in O(2) levels known to have occurred over evolutionary time could, by influencing adhesion systems, have contributed to early symbiotic events in unicellular organisms and to the emergence of multicellularity. It is not my intention to be exhaustive in these domains, which are far from my own field of study. Rather this article is meant to provoke and stimulate thinking about molecular evolution involving O(2) sensing and signaling during eras of geologic and atmospheric change that might inform modern studies on development and disease.}, } @article {pmid22622805, year = {2013}, author = {Colombelli, J and Solon, J}, title = {Force communication in multicellular tissues addressed by laser nanosurgery.}, journal = {Cell and tissue research}, volume = {352}, number = {1}, pages = {133-147}, doi = {10.1007/s00441-012-1445-1}, pmid = {22622805}, issn = {1432-0878}, mesh = {Animals ; Biomechanical Phenomena ; Cell Communication ; Cytoskeleton/metabolism ; Humans ; Laser Capture Microdissection/methods ; Laser Therapy/*methods ; *Mechanotransduction, Cellular ; Morphogenesis ; }, abstract = {Cell contractility is a prominent mechanism driving multicellular tissue development and remodeling. Forces originated by the actomyosin cytoskeleton not only act within the cell body but can also propagate many layers away from the contraction source and grant tissues the ability to organize collectively and to achieve robust remodeling through development. Tissue tension is being thoroughly investigated in model organisms and increasing evidence is revealing the major role played by the communication, dynamics and propagation of cell-to-cell physical forces in multicellular remodeling. Recently, pulsed-laser-based surgery has fostered in vivo experimental studies to investigate intracellular and supracellular forces in action. The technique offers a unique method to perturb mechanical equilibrium in a subpopulation of cells or in a single cell, while the overall tissue remains intact. In particular, improved ablation precision with short laser pulses and the combination of this technique with biophysical models now allow an in-depth understanding of the role of cellular mechanics in tissue morphogenesis. We first characterize laser ablation modes available to perform intracellular, cellular, or multi-cellular ablation via the example of the model monolayer tissue of the amnioserosa of Drosophila by relating subnanosecond laser pulse energy to ablation efficiency and the probability of cavitation bubble formation. We then review recent laser nanosurgery experiments that have been performed in cultured cells and that tackle actomyosin mechanics and provide molecular insights into force-sensing mechanisms. We finally review studies showing the central role of laser ablation in revealing the nature and orientation of forces involved in intracellular contractility and force mechanosensing in tissue development, e.g., axis elongation, branching morphogenesis, or tissue invagination. We discuss the perspectives offered by the technique in force-based cell-cell communication and mechanosensing pathways.}, } @article {pmid22609469, year = {2012}, author = {Nahalka, J}, title = {Glycocodon theory--the first table of glycocodons.}, journal = {Journal of theoretical biology}, volume = {307}, number = {}, pages = {193-204}, doi = {10.1016/j.jtbi.2012.05.010}, pmid = {22609469}, issn = {1095-8541}, mesh = {Amino Acid Sequence ; Campylobacter/enzymology ; Crystallization ; Galectin 3/chemistry ; *Genetic Code ; Glycocalyx/chemistry/genetics ; Glycoproteins/chemistry/metabolism ; Hexosyltransferases/chemistry ; Humans ; Lectins/chemistry ; Membrane Proteins/chemistry ; *Models, Genetic ; Models, Molecular ; Molecular Sequence Data ; Peptides/chemistry/metabolism ; Polysaccharides/chemistry/*genetics ; Pseudomonas syringae/metabolism ; Sequence Alignment ; }, abstract = {Hydrophobic cellular membranes separate cells from an environment that is generally based on water. Therefore, it is not surprising that hydrophilic glycans and glycoproteins are exposed on the lipidic surface of membranes and that the glycocalyx has evolved in all basic cell types. During the evolution of multicellular life, the surface exposed protein-glycan interactions were taken as the origin of the language of cell-cell communication. The bioinformatics analysis presented here reveals that the amino acid triplets, the glycocodons, can be deduced for each glycan letter (monosaccharide). This theory proposes to distinguish between the "sugar code" (the sugar sequence) and the "glycocode" (evolutionary selected amino acids recognising the mono-sugar). Similarly to genetic code, original glycocodons are related to G, A, V, and D amino acids. Modern glycocodons can be deduced from GAVD-glycocodons using hydropathic similarity. In general, the amino acid triplets can be assembled from one dipeptide that is specific to a monosaccharide plus a polar amino acid. This theory may shed a different light on the reason for WWD conservation in the active sites of oligosaccharyltransferases and for GGQ in the active sites of ribosomes.}, } @article {pmid22608515, year = {2012}, author = {Wang, F and Vandepoele, K and Van Lijsebettens, M}, title = {Tetraspanin genes in plants.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {190}, number = {}, pages = {9-15}, doi = {10.1016/j.plantsci.2012.03.005}, pmid = {22608515}, issn = {1873-2259}, mesh = {Evolution, Molecular ; Genes, Plant/*genetics ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; Plants/*genetics/*metabolism ; Tetraspanins/chemistry/*genetics/metabolism ; }, abstract = {Tetraspanins represent a four-transmembrane protein superfamily with a conserved structure and amino acid residues that are present in mammals, insects, fungi and plants. Tetraspanins interact with each other or with other membrane proteins to form tetraspanin-enriched microdomains that play important roles in development, pathogenesis and immune responses via facilitating cell-cell adhesion and fusion, ligand binding and intracellular trafficking. Here, we emphasize evolutionary aspects within the plant kingdom based on genomic sequence information. A phylogenetic tree based on 155 tetraspanin genes of 11 plant species revealed ancient and fast evolving clades. Tetraspanins were only present in multicellular plants, were often duplicated in the plant genomes and predicted by the electronic Fluorescent Pictograph for gene expression analysis to be either functionally redundant or divergent. Tetraspanins contain a large extracellular loop with conserved cysteines that provide the binding sites for the interactions. The Arabidopsis thaliana TETRASPANIN1/TORNADO2/EKEKO has a function in leaf and root patterning and TETRASPANIN3 was identified in the plasmodesmatal proteome, suggesting a role in cell-cell communication during plant development.}, } @article {pmid22608512, year = {2012}, author = {Brown, MW and Kolisko, M and Silberman, JD and Roger, AJ}, title = {Aggregative multicellularity evolved independently in the eukaryotic supergroup Rhizaria.}, journal = {Current biology : CB}, volume = {22}, number = {12}, pages = {1123-1127}, doi = {10.1016/j.cub.2012.04.021}, pmid = {22608512}, issn = {1879-0445}, mesh = {Adaptation, Biological/*physiology ; Base Sequence ; Bayes Theorem ; *Biological Evolution ; DNA, Complementary/genetics ; Genomics/methods ; Likelihood Functions ; Models, Genetic ; Molecular Sequence Data ; *Phylogeny ; Rhizaria/classification/*cytology/*genetics ; Sequence Analysis, DNA ; }, abstract = {Multicellular forms of life have evolved many times, independently giving rise to a diversity of organisms such as animals, plants, and fungi that together comprise the visible biosphere. Yet multicellular life is far more widespread among eukaryotes than just these three lineages. A particularly common form of multicellularity is a social aggregative fruiting lifestyle whereby individual cells associate to form a "fungus-like" sorocarp. This complex developmental process that requires the interaction of thousands of cells working in concert was made famous by the "cellular slime mold"Dictyostelium discoideum, which became an important model organism. Although sorocarpic protistan lineages have been identified in five of the major eukaryote groups, the ubiquitous and globally distributed species Guttulinopsis vulgaris has eluded proper classification. Here we demonstrate, by phylogenomic analyses of a 159-protein data set, that G. vulgaris is a member of Rhizaria and is thus the first member of this eukaryote supergroup known to be capable of aggregative multicellularity.}, } @article {pmid22600736, year = {2012}, author = {Hsu, DW and Chubb, JR and Muramoto, T and Pears, CJ and Mahadevan, LC}, title = {Dynamic acetylation of lysine-4-trimethylated histone H3 and H3 variant biology in a simple multicellular eukaryote.}, journal = {Nucleic acids research}, volume = {40}, number = {15}, pages = {7247-7256}, pmid = {22600736}, issn = {1362-4962}, support = {090904//Wellcome Trust/United Kingdom ; G120/1013/MRC_/Medical Research Council/United Kingdom ; G120/1013(75407)/MRC_/Medical Research Council/United Kingdom ; 081548/Z/06/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Acetylation/drug effects ; Amino Acid Substitution ; Dictyostelium/genetics/growth & development/*metabolism ; Gene Deletion ; Gene Expression ; Histone-Lysine N-Methyltransferase/genetics ; Histones/chemistry/genetics/*metabolism ; Hydroxamic Acids/pharmacology ; Lysine/*metabolism ; Methylation ; }, abstract = {Dynamic acetylation of all lysine-4-trimethylated histone H3 is a complex phenomenon involved in Immediate-early gene induction in metazoan eukaryotes. Higher eukaryotes express repeated copies of three closely related H3 variants, inaccessible to genetic analysis. We demonstrate conservation of these phenomena in Dictyostelium which has three single-copy H3 variant genes. Although dynamic acetylation is targeted to two H3 variants which are K4-trimethylated, K9-acetylation is preferentially targeted to one. In cells lacking Set1 methyltransferase and any detectable K4-trimethylation, dynamic acetylation is lost demonstrating a direct link between the two. Gene replacement to express mutated H3 variants reveals a novel interaction between K4-trimethylation on different variants. Cells expressing only one variant show defects in growth, and in induction of a UV-inducible gene, demonstrating the functional importance of variant expression. These studies confirm that dynamic acetylation targeted to H3K4me3 arose early in evolution and reveal a very high level of specificity of histone variant utilization in a simple multicellular eukaryote.}, } @article {pmid22595987, year = {2012}, author = {Hemmrich, G and Khalturin, K and Boehm, AM and Puchert, M and Anton-Erxleben, F and Wittlieb, J and Klostermeier, UC and Rosenstiel, P and Oberg, HH and Domazet-Loso, T and Sugimoto, T and Niwa, H and Bosch, TC}, title = {Molecular signatures of the three stem cell lineages in hydra and the emergence of stem cell function at the base of multicellularity.}, journal = {Molecular biology and evolution}, volume = {29}, number = {11}, pages = {3267-3280}, doi = {10.1093/molbev/mss134}, pmid = {22595987}, issn = {1537-1719}, mesh = {Animals ; Biological Evolution ; Cell Lineage/*genetics ; Cell Separation ; *Gene Expression Profiling ; Gene Expression Regulation ; Genetic Complementation Test ; Hydra/*cytology/*genetics ; Mice ; Phylogeny ; Staining and Labeling ; Stem Cells/*cytology/*metabolism ; Transcription Factors/genetics/metabolism ; Transcriptome/genetics ; }, abstract = {How distinct stem cell populations originate and whether there is a clear stem cell "genetic signature" remain poorly understood. Understanding the evolution of stem cells requires molecular profiling of stem cells in an animal at a basal phylogenetic position. In this study, using transgenic Hydra polyps, we reveal for each of the three stem cell populations a specific signature set of transcriptions factors and of genes playing key roles in cell type-specific function and interlineage communication. Our data show that principal functions of stem cell genes, such as maintenance of stemness and control of stem cell self-renewal and differentiation, arose very early in metazoan evolution. They are corroborating the view that stem cell types shared common, multifunctional ancestors, which achieved complexity through a stepwise segregation of function in daughter cells.}, } @article {pmid22589468, year = {2012}, author = {Kandasamy, MK and McKinney, EC and Roy, E and Meagher, RB}, title = {Plant vegetative and animal cytoplasmic actins share functional competence for spatial development with protists.}, journal = {The Plant cell}, volume = {24}, number = {5}, pages = {2041-2057}, pmid = {22589468}, issn = {1532-298X}, support = {R01 GM036397/GM/NIGMS NIH HHS/United States ; T32 GM007103/GM/NIGMS NIH HHS/United States ; GM 07103-35/GM/NIGMS NIH HHS/United States ; GM36397-25/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/*classification/genetics/*metabolism ; Archamoebae/genetics/metabolism ; Chlorophyta/genetics/metabolism ; Choanoflagellata/genetics/metabolism ; Ciona intestinalis/genetics/metabolism ; Phylogeny ; }, abstract = {Actin is an essential multifunctional protein encoded by two distinct ancient classes of genes in animals (cytoplasmic and muscle) and plants (vegetative and reproductive). The prevailing view is that each class of actin variants is functionally distinct. However, we propose that the vegetative plant and cytoplasmic animal variants have conserved functional competence for spatial development inherited from an ancestral protist actin sequence. To test this idea, we ectopically expressed animal and protist actins in Arabidopsis thaliana double vegetative actin mutants that are dramatically altered in cell and organ morphologies. We found that expression of cytoplasmic actins from humans and even a highly divergent invertebrate Ciona intestinalis qualitatively and quantitatively suppressed the root cell polarity and organ defects of act8 act7 mutants and moderately suppressed the root-hairless phenotype of act2 act8 mutants. By contrast, human muscle actins were unable to support prominently any aspect of plant development. Furthermore, actins from three protists representing Choanozoa, Archamoeba, and green algae efficiently suppressed all the phenotypes of both the plant mutants. Remarkably, these data imply that actin's competence to carry out a complex suite of processes essential for multicellular development was already fully developed in single-celled protists and evolved nonprogressively from protists to plants and animals.}, } @article {pmid22587123, year = {2012}, author = {Flenner, E and Janosi, L and Barz, B and Neagu, A and Forgacs, G and Kosztin, I}, title = {Kinetic Monte Carlo and cellular particle dynamics simulations of multicellular systems.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {85}, number = {3 Pt 1}, pages = {031907}, doi = {10.1103/PhysRevE.85.031907}, pmid = {22587123}, issn = {1550-2376}, mesh = {Animals ; Cell Aggregation/physiology ; Cell Communication/*physiology ; Cell Movement/physiology ; Computer Simulation ; Humans ; *Models, Biological ; Spheroids, Cellular/*physiology ; }, abstract = {Computer modeling of multicellular systems has been a valuable tool for interpreting and guiding in vitro experiments relevant to embryonic morphogenesis, tumor growth, angiogenesis and, lately, structure formation following the printing of cell aggregates as bioink particles. Here we formulate two computer simulation methods: (1) a kinetic Monte Carlo (KMC) and (2) a cellular particle dynamics (CPD) method, which are capable of describing and predicting the shape evolution in time of three-dimensional multicellular systems during their biomechanical relaxation. Our work is motivated by the need of developing quantitative methods for optimizing postprinting structure formation in bioprinting-assisted tissue engineering. The KMC and CPD model parameters are determined and calibrated by using an original computational-theoretical-experimental framework applied to the fusion of two spherical cell aggregates. The two methods are used to predict the (1) formation of a toroidal structure through fusion of spherical aggregates and (2) cell sorting within an aggregate formed by two types of cells with different adhesivities.}, } @article {pmid22581706, year = {2012}, author = {Somorjai, IM and Lohmann, JU and Holstein, TW and Zhao, Z}, title = {Stem cells: a view from the roots.}, journal = {Biotechnology journal}, volume = {7}, number = {6}, pages = {704-722}, doi = {10.1002/biot.201100349}, pmid = {22581706}, issn = {1860-7314}, mesh = {Animals ; Arabidopsis/cytology ; Cell Differentiation/genetics ; Cnidaria/cytology ; DNA Methylation ; Drosophila/cytology ; Epigenesis, Genetic ; Histones/metabolism ; Humans ; Mice ; MicroRNAs ; Stem Cell Niche ; Stem Cells/*cytology/*physiology ; }, abstract = {In both plants and animals, regeneration requires the activation of stem cells. This is possibly related to the origin and requirements of multicellularity. Although long diverged from a common ancestry, plant and animal models such as Arabidopsis, Drosophila and mouse share considerable similarities in stem cell regulation. This includes stem cell niche organisation, epigenetic modification of DNA and histones, and the role of small RNA machinery in differentiation and pluripotency states. Dysregulation of any of these can lead to premature ageing, patterning and specification defects, as well as cancers. Moreover, emerging basal animal and plant systems are beginning to provide important clues concerning the diversity and evolutionary history of stem cell regulatory mechanisms in eukaryotes. This review provides a comparative framework, highlighting both the commonalities and differences among groups, which should promote the intelligent design of artificial stem cell systems, and thereby fuel the field of biomaterials science.}, } @article {pmid22580093, year = {2012}, author = {Gardner, MB and Baumgarth, N and Fell, A and McSorley, SJ and Solnick, JV and Bevins, CL}, title = {Meeting report: a symposium on the evolution of common molecular pathways underlying innate immunity.}, journal = {Microbes and infection}, volume = {14}, number = {9}, pages = {667-671}, doi = {10.1016/j.micinf.2012.04.001}, pmid = {22580093}, issn = {1769-714X}, support = {R01 AI032738/AI/NIAID NIH HHS/United States ; R37 AI032738/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; California ; *Evolution, Molecular ; Humans ; *Immunity, Innate ; Models, Animal ; Models, Biological ; Molecular Biology ; }, abstract = {The University of California, Davis hosted a symposium on innate immunity in January 2012. Professors Bruce Beutler, Jules Hoffmann, Luke O'Neill and Pamela Ronald discussed their research on mechanisms that multicellular organisms use to recognize microbes.}, } @article {pmid22575034, year = {2012}, author = {Truong, F and Yoo, TH and Lampo, TJ and Tirrell, DA}, title = {Two-strain, cell-selective protein labeling in mixed bacterial cultures.}, journal = {Journal of the American Chemical Society}, volume = {134}, number = {20}, pages = {8551-8556}, pmid = {22575034}, issn = {1520-5126}, support = {R01 GM062523/GM/NIGMS NIH HHS/United States ; }, mesh = {Alkynes/*metabolism ; Amino Acid Sequence ; Escherichia coli/*enzymology/genetics/metabolism ; Escherichia coli Proteins/*analysis/*genetics/metabolism ; Fluorescent Dyes/*analysis ; Glycine/*analogs & derivatives/genetics/metabolism ; Methionine-tRNA Ligase/genetics/*metabolism ; Molecular Sequence Data ; Protein Engineering/methods ; Proteomics/methods ; Staining and Labeling/methods ; }, abstract = {Cell-selective metabolic labeling of proteins with noncanonical amino acids enables the study of proteomic changes in specified subpopulations of complex multicellular systems. For example, azidonorleucine (Anl) and 2-aminooctynoic acid, both of which are activated by an engineered methionyl-tRNA synthetase (designated NLL-MetRS), are excluded from proteins made in wild-type cells but incorporated readily into proteins made in cells that carry NLL-MetRS. To expand the set of tools available for cell-selective metabolic labeling, we sought a MetRS variant capable of activating propargylglycine (Pra). Pra was chosen as the target amino acid because its alkynyl side chain can be selectively and efficiently conjugated to azide-functionalized fluorescence probes and affinity tags. Directed evolution, using active-site randomization and error-prone PCR, yielded a MetRS variant (designated PraRS) capable of incorporating Pra at near-quantitative levels into proteins made in a Met-auxotrophic strain of Escherichia coli cultured in Met-depleted media. Proteins made in E. coli strains expressing PraRS were labeled with Pra in Met-supplemented media as shown by in-gel fluorescence after conjugation to Cy5-azide. The combined use of NLL-MetRS and PraRS enabled differential, cell-selective labeling of marker proteins derived from two bacterial strains cocultured in media supplemented with Met, Anl, and Pra. Treatment of the mixed marker proteins by sequential strain-promoted and copper(I)-catalyzed cycloadditions allowed straightforward identification of the cellular origin of each protein.}, } @article {pmid22572958, year = {2012}, author = {Batsios, P and Peter, T and Baumann, O and Stick, R and Meyer, I and Gräf, R}, title = {A lamin in lower eukaryotes?.}, journal = {Nucleus (Austin, Tex.)}, volume = {3}, number = {3}, pages = {237-243}, pmid = {22572958}, issn = {1949-1042}, mesh = {Alkyl and Aryl Transferases/chemistry/metabolism ; Animals ; Cell Nucleus/metabolism ; Centrosome/metabolism ; Dictyostelium/metabolism ; Lamins/chemistry/*metabolism ; Nuclear Envelope/metabolism ; Protein Processing, Post-Translational ; Protozoan Proteins/chemistry/*metabolism ; }, abstract = {Lamins are the major components of the nuclear lamina and serve not only as a mechanical support, but are also involved in chromatin organization, epigenetic regulation, transcription and mitotic events. Despite these universal tasks, lamins have so far been found only in metazoans. Yet, recently we have identified Dictyostelium NE81 as the first lamin-like protein in a lower eukaryote. Based on the current knowledge, we draw a model for nuclear envelope organization in Dictyostelium in this Extra View and we review the experimental data that justified this classification. Furthermore we provide unpublished data underscoring the requirement of posttranslational CaaX-box processing for proper protein localization at the nuclear envelope. Sequence comparison of NE81 sequences from four Dictyostelia with bona fide lamins illustrates the evolutional relationship between these proteins. Under certain conditions these usually unicellular social amoebae congregate to form a multicellular body. We propose that the evolution of the lamin-like NE81 went along with the invention of multicellularity.}, } @article {pmid22567377, year = {2012}, author = {Brannan, K and Bentley, DL}, title = {Control of Transcriptional Elongation by RNA Polymerase II: A Retrospective.}, journal = {Genetics research international}, volume = {2012}, number = {}, pages = {170173}, pmid = {22567377}, issn = {2090-3162}, support = {R01 GM063873/GM/NIGMS NIH HHS/United States ; T32 GM008730/GM/NIGMS NIH HHS/United States ; }, abstract = {The origins of our current understanding of control of transcription elongation lie in pioneering experiments that mapped RNA polymerase II on viral and cellular genes. These studies first uncovered the surprising excess of polymerase molecules that we now know to be situated at the at the 5' ends of most genes in multicellular organisms. The pileup of pol II near transcription start sites reflects a ubiquitous bottle-neck that limits elongation right at the start of the transcription elongation. Subsequent seminal work identified conserved protein factors that positively and negatively control the flux of polymerase through this bottle-neck, and make a major contribution to control of gene expression.}, } @article {pmid22566026, year = {2012}, author = {Xu, K and Buchsbaum, RJ}, title = {Isolation of mammary epithelial cells from three-dimensional mixed-cell spheroid co-culture.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {62}, pages = {}, pmid = {22566026}, issn = {1940-087X}, mesh = {Animals ; Coculture Techniques/*methods ; Epithelial Cells/cytology ; Humans ; Mammary Glands, Animal/*cytology ; Mammary Glands, Human/*cytology ; Spheroids, Cellular/*cytology ; }, abstract = {While enormous efforts have gone into identifying signaling pathways and molecules involved in normal and malignant cell behaviors(1-2), much of this work has been done using classical two-dimensional cell culture models, which allow for easy cell manipulation. It has become clear that intracellular signaling pathways are affected by extracellular forces, including dimensionality and cell surface tension(3-4). Multiple approaches have been taken to develop three-dimensional models that more accurately represent biologic tissue architecture(3). While these models incorporate multi-dimensionality and architectural stresses, study of the consequent effects on cells is less facile than in two-dimensional tissue culture due to the limitations of the models and the difficulty in extracting cells for subsequent analysis. The important role of the microenvironment around tumors in tumorigenesis and tumor behavior is becoming increasingly recognized(4). Tumor stroma is composed of multiple cell types and extracellular molecules. During tumor development there are bidirectional signals between tumor cells and stromal cells(5). Although some factors participating in tumor-stroma co-evolution have been identified, there is still a need to develop simple techniques to systematically identify and study the full array of these signals(6). Fibroblasts are the most abundant cell type in normal or tumor-associated stromal tissues, and contribute to deposition and maintenance of basement membrane and paracrine growth factors(7). Many groups have used three dimensional culture systems to study the role of fibroblasts on various cellular functions, including tumor response to therapies, recruitment of immune cells, signaling molecules, proliferation, apoptosis, angiogenesis, and invasion(8-15). We have optimized a simple method for assessing the effects of mammary fibroblasts on mammary epithelial cells using a commercially available extracellular matrix model to create three-dimensional cultures of mixed cell populations (co-cultures)(16-22). With continued co-culture the cells form spheroids with the fibroblasts clustering in the interior and the epithelial cells largely on the exterior of the spheroids and forming multi-cellular projections into the matrix. Manipulation of the fibroblasts that leads to altered epithelial cell invasiveness can be readily quantified by changes in numbers and length of epithelial projections(23). Furthermore, we have devised a method for isolating epithelial cells out of three-dimensional co-culture that facilitates analysis of the effects of fibroblast exposure on epithelial behavior. We have found that the effects of co-culture persist for weeks after epithelial cell isolation, permitting ample time to perform multiple assays. This method is adaptable to cells of varying malignant potential and requires no specialized equipment. This technique allows for rapid evaluation of in vitro cell models under multiple conditions, and the corresponding results can be compared to in vivo animal tissue models as well as human tissue samples.}, } @article {pmid22564088, year = {2012}, author = {Noonin, C and Lin, X and Jiravanichpaisal, P and Söderhäll, K and Söderhäll, I}, title = {Invertebrate hematopoiesis: an anterior proliferation center as a link between the hematopoietic tissue and the brain.}, journal = {Stem cells and development}, volume = {21}, number = {17}, pages = {3173-3186}, doi = {10.1089/scd.2012.0077}, pmid = {22564088}, issn = {1557-8534}, mesh = {Animals ; Astacoidea/*cytology/metabolism/physiology ; Brain/*cytology/metabolism/physiology ; Bromodeoxyuridine/metabolism ; Cell Count ; Cell Differentiation ; Cell Nucleus/metabolism ; *Cell Proliferation ; Cells, Cultured ; Gastric Mucosa/metabolism ; *Hematopoiesis ; Hematopoietic System/cytology/metabolism ; Hemocytes/*cytology/metabolism ; Lipopolysaccharides ; Microscopy, Electron, Transmission ; Mitosis ; Reactive Oxygen Species/metabolism ; Staining and Labeling ; Stomach/cytology/physiology ; }, abstract = {During evolution, the innate and adaptive immune systems were developed to protect organisms from non-self substances. The innate immune system is phylogenetically more ancient and is present in most multicellular organisms, whereas adaptive responses are restricted to vertebrates. Arthropods lack the blood cells of the lymphoid lineage and oxygen-carrying erythrocytes, making them suitable model animals for studying the regulation of the blood cells of the innate immune system. Many crustaceans have a long life span and need to continuously synthesize blood cells, in contrast to many insects. The hematopoietic tissue (HPT) of Pacifastacus leniusculus provides a simple model for studying hematopoiesis, because the tissue can be isolated, and the proliferation of stem cells and their differentiation can be studied both in vivo and in vitro. Here, we demonstrate new findings of a physical link between the HPT and the brain. Actively proliferating cells were localized to an anterior proliferation center (APC) in the anterior part of the tissue near the area linking the HPT to the brain, whereas more differentiated cells were detected in the posterior part. The central areas of HPT expand in response to lipopolysaccharide-induced blood loss. Cells isolated from the APC divide rapidly and form cell clusters in vitro; conversely, the cells from the remaining HPT form monolayers, and they can be induced to differentiate in vitro. Our findings offer an opportunity to learn more about invertebrate hematopoiesis and its connection to the central nervous system, thereby obtaining new information about the evolution of different blood and nerve cell lineages.}, } @article {pmid22562152, year = {2012}, author = {Greer, SN and Metcalf, JL and Wang, Y and Ohh, M}, title = {The updated biology of hypoxia-inducible factor.}, journal = {The EMBO journal}, volume = {31}, number = {11}, pages = {2448-2460}, pmid = {22562152}, issn = {1460-2075}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Apoptosis Regulatory Proteins ; Basic Helix-Loop-Helix Transcription Factors/*metabolism ; Carrier Proteins/metabolism ; Embryonic Development ; Humans ; Hypoxia/*metabolism ; Hypoxia-Inducible Factor 1/antagonists & inhibitors/*metabolism ; Immunity ; Membrane Proteins/metabolism ; Mice ; Oxygen/*metabolism ; Receptors, Notch/metabolism ; Repressor Proteins ; Sirtuin 3/metabolism ; Thyroid Hormones/metabolism ; }, abstract = {Oxygen is essential for eukaryotic life and is inextricably linked to the evolution of multicellular organisms. Proper cellular response to changes in oxygen tension during normal development or pathological processes, such as cardiovascular disease and cancer, is ultimately regulated by the transcription factor, hypoxia-inducible factor (HIF). Over the past decade, unprecedented molecular insight has been gained into the mammalian oxygen-sensing pathway involving the canonical oxygen-dependent prolyl-hydroxylase domain-containing enzyme (PHD)-von Hippel-Lindau tumour suppressor protein (pVHL) axis and its connection to cellular metabolism. Here we review recent notable advances in the field of hypoxia that have shaped a more complex model of HIF regulation and revealed unique roles of HIF in a diverse range of biological processes, including immunity, development and stem cell biology.}, } @article {pmid22550341, year = {2012}, author = {Suga, H and Dacre, M and de Mendoza, A and Shalchian-Tabrizi, K and Manning, G and Ruiz-Trillo, I}, title = {Genomic survey of premetazoans shows deep conservation of cytoplasmic tyrosine kinases and multiple radiations of receptor tyrosine kinases.}, journal = {Science signaling}, volume = {5}, number = {222}, pages = {ra35}, doi = {10.1126/scisignal.2002733}, pmid = {22550341}, issn = {1937-9145}, support = {206883/ERC_/European Research Council/International ; HG004164/HG/NHGRI NIH HHS/United States ; }, mesh = {Base Sequence ; Cytoplasm/enzymology/*genetics ; Eukaryota/enzymology/*genetics ; *Evolution, Molecular ; Genome/*physiology ; Molecular Sequence Data ; *Phylogeny ; Receptor Protein-Tyrosine Kinases/*genetics ; }, abstract = {The evolution of multicellular metazoans from a unicellular ancestor is one of the most important advances in the history of life. Protein tyrosine kinases play important roles in cell-to-cell communication, cell adhesion, and differentiation in metazoans; thus, elucidating their origins and early evolution is crucial for understanding the origin of metazoans. Although tyrosine kinases exist in choanoflagellates, few data are available about their existence in other premetazoan lineages. To unravel the origin of tyrosine kinases, we performed a genomic and polymerase chain reaction (PCR)-based survey of the genes that encode tyrosine kinases in the two described filasterean species, Capsaspora owczarzaki and Ministeria vibrans, the closest relatives to the Metazoa and Choanoflagellata clades. We present 103 tyrosine kinase-encoding genes identified in the whole genome sequence of C. owczarzaki and 15 tyrosine kinase-encoding genes cloned by PCR from M. vibrans. Through detailed phylogenetic analysis, comparison of the organizations of the protein domains, and resequencing and revision of tyrosine kinase sequences previously found in some whole genome sequences, we demonstrate that the basic repertoire of metazoan cytoplasmic tyrosine kinases was established before the divergence of filastereans from the Metazoa and Choanoflagellata clades. In contrast, the receptor tyrosine kinases diversified extensively in each of the filasterean, choanoflagellate, and metazoan clades. This difference in the divergence patterns between cytoplasmic tyrosine kinases and receptor tyrosine kinases suggests that receptor tyrosine kinases that had been used for receiving environmental cues were subsequently recruited as a communication tool between cells at the onset of metazoan multicellularity.}, } @article {pmid22549587, year = {2012}, author = {Liu, H and Jiang, D and Chi, F and Zhao, B}, title = {The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation.}, journal = {Protein & cell}, volume = {3}, number = {4}, pages = {291-304}, pmid = {22549587}, issn = {1674-8018}, mesh = {Animals ; Cell Differentiation ; Cell Proliferation ; Drosophila ; Drosophila Proteins/*metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/*metabolism ; Mesenchymal Stem Cells/cytology/metabolism ; Neoplastic Stem Cells/cytology/metabolism ; Nuclear Proteins/metabolism ; Protein Serine-Threonine Kinases/*metabolism ; Signal Transduction ; Stem Cells/*cytology/metabolism ; Transcription Factors/metabolism ; }, abstract = {Stem cells and progenitor cells are the cells of origin for multi-cellular organisms and organs. They play key roles during development and their dysregulation gives rise to human diseases such as cancer. The recent development of induced pluripotent stem cell (iPSC) technology which converts somatic cells to stem-like cells holds great promise for regenerative medicine. Nevertheless, the understanding of proliferation, differentiation, and self-renewal of stem cells and organ-specific progenitor cells is far from clear. Recently, the Hippo pathway was demonstrated to play important roles in these processes. The Hippo pathway is a newly established signaling pathway with critical functions in limiting organ size and suppressing tumorigenesis. This pathway was first found to inhibit cell proliferation and promote apoptosis, therefore regulating cell number and organ size in both Drosophila and mammals. However, in several organs, disturbance of the pathway leads to specific expansion of the progenitor cell compartment and manipulation of the pathway in embryonic stem cells strongly affects their self-renewal and differentiation. In this review, we summarize current observations on roles of the Hippo pathway in different types of stem cells and discuss how these findings changed our view on the Hippo pathway in organ development and tumorigenesis.}, } @article {pmid22543690, year = {2012}, author = {Birke, H and Müller, SJ and Rother, M and Zimmer, AD and Hoernstein, SN and Wesenberg, D and Wirtz, M and Krauss, GJ and Reski, R and Hell, R}, title = {The relevance of compartmentation for cysteine synthesis in phototrophic organisms.}, journal = {Protoplasma}, volume = {249 Suppl 2}, number = {}, pages = {S147-55}, pmid = {22543690}, issn = {1615-6102}, mesh = {*Cell Compartmentation ; Cysteine/*biosynthesis ; *Phototrophic Processes ; Plant Proteins/metabolism ; Subcellular Fractions/metabolism ; Sulfur/metabolism ; }, abstract = {In the vascular plant Arabidopsis thaliana, synthesis of cysteine and its precursors O-acetylserine and sulfide is distributed between the cytosol, chloroplasts, and mitochondria. This compartmentation contributes to regulation of cysteine synthesis. In contrast to Arabidopsis, cysteine synthesis is exclusively restricted to chloroplasts in the unicellular green alga Chlamydomonas reinhardtii. Thus, the question arises, whether specification of compartmentation was driven by multicellularity and specified organs and tissues. The moss Physcomitrella patens colonizes land but is still characterized by a simple morphology compared to vascular plants. It was therefore used as model organism to study evolution of compartmented cysteine synthesis. The presence of O-acetylserine(thiol)lyase (OAS-TL) proteins, which catalyze the final step of cysteine synthesis, in different compartments was applied as criterion. Purification and characterization of native OAS-TL proteins demonstrated the presence of five OAS-TL protein species encoded by two genes in Physcomitrella. At least one of the gene products is dual targeted to plastids and cytosol, as shown by combination of GFP fusion localization studies, purification of chloroplasts, and identification of N termini from native proteins. The bulk of OAS-TL protein is targeted to plastids, whereas there is no evidence for a mitochondrial OAS-TL isoform and only a minor part of OAS-TL protein is localized in the cytosol. This demonstrates that subcellular diversification of cysteine synthesis is already initialized in Physcomitrella but appears to gain relevance later during evolution of vascular plants.}, } @article {pmid22543423, year = {2013}, author = {Ereskovsky, AV and Renard, E and Borchiellini, C}, title = {Cellular and molecular processes leading to embryo formation in sponges: evidences for high conservation of processes throughout animal evolution.}, journal = {Development genes and evolution}, volume = {223}, number = {1-2}, pages = {5-22}, pmid = {22543423}, issn = {1432-041X}, mesh = {Animals ; *Biological Evolution ; Porifera/classification/cytology/*embryology/physiology ; Reproduction, Asexual ; Signal Transduction ; }, abstract = {The emergence of multicellularity is regarded as one of the major evolutionary events of life. This transition unicellularity/pluricellularity was acquired independently several times (King 2004). The acquisition of multicellularity implies the emergence of cellular cohesion and means of communication, as well as molecular mechanisms enabling the control of morphogenesis and body plan patterning. Some of these molecular tools seem to have predated the acquisition of multicellularity while others are regarded as the acquisition of specific lineages. Morphogenesis consists in the spatial migration of cells or cell layers during embryonic development, metamorphosis, asexual reproduction, growth, and regeneration, resulting in the formation and patterning of a body. In this paper, our aim is to review what is currently known concerning basal metazoans--sponges' morphogenesis from the tissular, cellular, and molecular points of view--and what remains to elucidate. Our review attempts to show that morphogenetic processes found in sponges are as diverse and complex as those found in other animals. In true epithelial sponges (Homoscleromorpha), as well as in others, we find similar cell/layer movements, cellular shape changes involved in major morphogenetic processes such as embryogenesis or larval metamorphosis. Thus, sponges can provide information enabling us to better understand early animal evolution at the molecular level but also at the cell/cell layer level. Indeed, comparison of molecular tools will only be of value if accompanied by functional data and expression studies during morphogenetic processes.}, } @article {pmid22535467, year = {2012}, author = {Wilson, IB}, title = {The class I α1,2-mannosidases of Caenorhabditis elegans.}, journal = {Glycoconjugate journal}, volume = {29}, number = {4}, pages = {173-179}, pmid = {22535467}, issn = {1573-4986}, mesh = {Animals ; Caenorhabditis elegans/*enzymology/metabolism ; Endoplasmic Reticulum/enzymology/metabolism ; Genome, Helminth ; Golgi Apparatus/enzymology/metabolism ; Mannans/chemistry/metabolism ; Mannosidases/*chemistry/classification ; Molecular Sequence Data ; Phylogeny ; Pichia/metabolism ; Polysaccharides/chemistry/metabolism ; }, abstract = {During the biosynthesis of N-glycans in multicellular eukaryotes, glycans with the compositions Man(5)GlcNAc(2-3) are key intermediates. However, to reach this 'decision point', these N-glycans are first processed from Glc(3)Man(9)GlcNAc(2) through to Man(5)GlcNAc(2) by a number of glycosidases, whereby up to four α1-2-linked mannose residues are removed by class I mannosidases (glycohydrolase family 47). Whereas in the yeast Saccharomyces cerevisiae there are maximally three members of this protein family, in higher organisms there are multiple class I mannosidases residing in the endoplasmic reticulum and Golgi apparatus. The genome of the model nematode Caenorhabditis elegans encodes seven members of this protein family, whereby four are predicted to be classical processing mannosidases and three are related proteins with roles in quality control. In this study, cDNAs encoding the four predicted mannosidases were cloned and expressed in Pichia pastoris and the activity of these enzymes, designated MANS-1, MANS-2, MANS-3 and MANS-4, was verified. The first two can, dependent on the incubation time, remove three to four residues from Man(9)GlcNAc(2), whereas the action of the other two results in the appearance of the B isomer of Man(8)GlcNAc(2); together the complementary activities of these enzymes result in processing to Man(5)GlcNAc(2). With these data, another gap is closed in our understanding of the N-glycan biosynthesis pathway of the nematode worm.}, } @article {pmid22534682, year = {2012}, author = {de Almeida, M and de Almeida, CV and Mendes Graner, E and Ebling Brondani, G and Fiori de Abreu-Tarazi, M}, title = {Pre-procambial cells are niches for pluripotent and totipotent stem-like cells for organogenesis and somatic embryogenesis in the peach palm: a histological study.}, journal = {Plant cell reports}, volume = {31}, number = {8}, pages = {1495-1515}, pmid = {22534682}, issn = {1432-203X}, mesh = {Arecaceae/*cytology/*embryology ; Cambium/*cytology ; Cell Count ; Cell Differentiation ; Cell Nucleus/metabolism ; *Organogenesis ; Plant Vascular Bundle/cytology/physiology ; Pluripotent Stem Cells/*cytology/metabolism ; Regeneration/physiology ; Seeds/cytology/embryology ; *Stem Cell Niche ; Totipotent Stem Cells/*cytology/metabolism ; }, abstract = {UNLABELLED: The direct induction of adventitious buds and somatic embryos from explants is a morphogenetic process that is under the influence of exogenous plant growth regulators and its interactions with endogenous phytohormones. We performed an in vitro histological analysis in peach palm (Bactris gasipaes Kunth) shoot apexes and determined that the positioning of competent cells and their interaction with neighboring cells, under the influence of combinations of exogenously applied growth regulators (NAA/BAP and NAA/TDZ), allows the pre-procambial cells (PPCs) to act in different morphogenic pathways to establish niche competent cells. It is likely that there has been a habituation phenomenon during the regeneration and development of the microplants. This includes promoting the tillering of primary or secondary buds due to culturing in the absence of NAA/BAP or NAA/TDZ after a period in the presence of these growth regulators. Histological analyses determined that the adventitious roots were derived from the dedifferentiation of the parenchymal cells located in the basal region of the adventitious buds, with the establishment of rooting pole, due to an auxin gradient. Furthermore, histological and histochemical analyses allowed us to characterize how the PPCs provide niches for multipotent, pluripotent and totipotent stem-like cells for vascular differentiation, organogenesis and somatic embryogenesis in the peach palm. The histological and histochemical analyses also allowed us to detect the unicellular or multicellular origin of somatic embryogenesis. Therefore, our results indicate that the use of growth regulators in microplants can lead to habituation and to different morphogenic pathways leading to potential niche establishment, depending on the positioning of the competent cells and their interaction with neighboring cells.

KEY MESSAGE: Our results indicate that the use of growth regulators in microplants can lead to habituation and to different morphogenic pathways leading to potential niche establishment, depending on the positioning of the competent cells and their interaction with neighboring cells.}, } @article {pmid22517163, year = {2012}, author = {Peters, SE and Gaines, RR}, title = {Formation of the 'Great Unconformity' as a trigger for the Cambrian explosion.}, journal = {Nature}, volume = {484}, number = {7394}, pages = {363-366}, pmid = {22517163}, issn = {1476-4687}, mesh = {Animals ; Aquatic Organisms/classification/cytology ; *Biological Evolution ; Ecosystem ; Fossils ; Geologic Sediments/*chemistry ; Geology ; History, Ancient ; Hydrogen-Ion Concentration ; North America ; Seawater/chemistry ; Soil/chemistry ; }, abstract = {The transition between the Proterozoic and Phanerozoic eons, beginning 542 million years (Myr) ago, is distinguished by the diversification of multicellular animals and by their acquisition of mineralized skeletons during the Cambrian period. Considerable progress has been made in documenting and more precisely correlating biotic patterns in the Neoproterozoic-Cambrian fossil record with geochemical and physical environmental perturbations, but the mechanisms responsible for those perturbations remain uncertain. Here we use new stratigraphic and geochemical data to show that early Palaeozoic marine sediments deposited approximately 540-480 Myr ago record both an expansion in the area of shallow epicontinental seas and anomalous patterns of chemical sedimentation that are indicative of increased oceanic alkalinity and enhanced chemical weathering of continental crust. These geochemical conditions were caused by a protracted period of widespread continental denudation during the Neoproterozoic followed by extensive physical reworking of soil, regolith and basement rock during the first continental-scale marine transgression of the Phanerozoic. The resultant globally occurring stratigraphic surface, which in most regions separates continental crystalline basement rock from much younger Cambrian shallow marine sedimentary deposits, is known as the Great Unconformity. Although Darwin and others have interpreted this widespread hiatus in sedimentation on the continents as a failure of the geologic record, this palaeogeomorphic surface represents a unique physical environmental boundary condition that affected seawater chemistry during a time of profound expansion of shallow marine habitats. Thus, the formation of the Great Unconformity may have been an environmental trigger for the evolution of biomineralization and the 'Cambrian explosion' of ecologic and taxonomic diversity following the Neoproterozoic emergence of animals.}, } @article {pmid22513108, year = {2012}, author = {Charrier, B and Le Bail, A and de Reviers, B}, title = {Plant Proteus: brown algal morphological plasticity and underlying developmental mechanisms.}, journal = {Trends in plant science}, volume = {17}, number = {8}, pages = {468-477}, doi = {10.1016/j.tplants.2012.03.003}, pmid = {22513108}, issn = {1878-4372}, mesh = {*Adaptation, Biological ; Biological Evolution ; Cell Division ; Environment ; Mechanotransduction, Cellular ; *Morphogenesis ; Phaeophyta/classification/genetics/*physiology ; Phylogeny ; Signal Transduction ; Species Specificity ; }, abstract = {Brown algae are multicellular photosynthetic marine organisms, ubiquitous on rocky intertidal shores at cold and temperate latitudes. Nevertheless, little is known about many aspects of their biology, particularly their development. Given their phylogenetic distance (1.6 billion years) from other plant organisms (land plants, and green and red algae), brown algae harbor a high, as-yet undiscovered diversity of biological mechanisms governing their development. They also show great morphological plasticity, responding to specific environmental constraints, such as sea currents, reduced light availability, grazer attacks, desiccation and UV exposure. Here, we show that brown algal morphogenesis is rather simple and flexible, and review recent genomic data on the cellular and molecular mechanisms known to date that can possibly account for this developmental strategy.}, } @article {pmid22511858, year = {2012}, author = {Rodrigues, JF and Rankin, DJ and Rossetti, V and Wagner, A and Bagheri, HC}, title = {Differences in cell division rates drive the evolution of terminal differentiation in microbes.}, journal = {PLoS computational biology}, volume = {8}, number = {4}, pages = {e1002468}, pmid = {22511858}, issn = {1553-7358}, mesh = {Cell Communication/*genetics ; Cell Differentiation/*genetics ; Cell Division ; Clonal Evolution/*genetics ; Computer Simulation ; Cyanobacteria/*genetics ; *Models, Genetic ; }, abstract = {Multicellular differentiated organisms are composed of cells that begin by developing from a single pluripotent germ cell. In many organisms, a proportion of cells differentiate into specialized somatic cells. Whether these cells lose their pluripotency or are able to reverse their differentiated state has important consequences. Reversibly differentiated cells can potentially regenerate parts of an organism and allow reproduction through fragmentation. In many organisms, however, somatic differentiation is terminal, thereby restricting the developmental paths to reproduction. The reason why terminal differentiation is a common developmental strategy remains unexplored. To understand the conditions that affect the evolution of terminal versus reversible differentiation, we developed a computational model inspired by differentiating cyanobacteria. We simulated the evolution of a population of two cell types -nitrogen fixing or photosynthetic- that exchange resources. The traits that control differentiation rates between cell types are allowed to evolve in the model. Although the topology of cell interactions and differentiation costs play a role in the evolution of terminal and reversible differentiation, the most important factor is the difference in division rates between cell types. Faster dividing cells always evolve to become the germ line. Our results explain why most multicellular differentiated cyanobacteria have terminally differentiated cells, while some have reversibly differentiated cells. We further observed that symbioses involving two cooperating lineages can evolve under conditions where aggregate size, connectivity, and differentiation costs are high. This may explain why plants engage in symbiotic interactions with diazotrophic bacteria.}, } @article {pmid22507701, year = {2012}, author = {Rogozin, IB and Carmel, L and Csuros, M and Koonin, EV}, title = {Origin and evolution of spliceosomal introns.}, journal = {Biology direct}, volume = {7}, number = {}, pages = {11}, pmid = {22507701}, issn = {1745-6150}, support = {Z01LM000073-12/LM/NLM NIH HHS/United States ; //Intramural NIH HHS/United States ; }, mesh = {Alternative Splicing ; Animals ; Base Sequence ; Conserved Sequence ; Eukaryota/chemistry/classification/genetics ; *Evolution, Molecular ; Exons ; Genetics, Population ; Genome ; *Introns ; Phylogeny ; RNA Splice Sites ; Selection, Genetic ; Spliceosomes/chemistry/*genetics ; Untranslated Regions ; }, abstract = {Evolution of exon-intron structure of eukaryotic genes has been a matter of long-standing, intensive debate. The introns-early concept, later rebranded 'introns first' held that protein-coding genes were interrupted by numerous introns even at the earliest stages of life's evolution and that introns played a major role in the origin of proteins by facilitating recombination of sequences coding for small protein/peptide modules. The introns-late concept held that introns emerged only in eukaryotes and new introns have been accumulating continuously throughout eukaryotic evolution. Analysis of orthologous genes from completely sequenced eukaryotic genomes revealed numerous shared intron positions in orthologous genes from animals and plants and even between animals, plants and protists, suggesting that many ancestral introns have persisted since the last eukaryotic common ancestor (LECA). Reconstructions of intron gain and loss using the growing collection of genomes of diverse eukaryotes and increasingly advanced probabilistic models convincingly show that the LECA and the ancestors of each eukaryotic supergroup had intron-rich genes, with intron densities comparable to those in the most intron-rich modern genomes such as those of vertebrates. The subsequent evolution in most lineages of eukaryotes involved primarily loss of introns, with only a few episodes of substantial intron gain that might have accompanied major evolutionary innovations such as the origin of metazoa. The original invasion of self-splicing Group II introns, presumably originating from the mitochondrial endosymbiont, into the genome of the emerging eukaryote might have been a key factor of eukaryogenesis that in particular triggered the origin of endomembranes and the nucleus. Conversely, splicing errors gave rise to alternative splicing, a major contribution to the biological complexity of multicellular eukaryotes. There is no indication that any prokaryote has ever possessed a spliceosome or introns in protein-coding genes, other than relatively rare mobile self-splicing introns. Thus, the introns-first scenario is not supported by any evidence but exon-intron structure of protein-coding genes appears to have evolved concomitantly with the eukaryotic cell, and introns were a major factor of evolution throughout the history of eukaryotes.}, } @article {pmid22474612, year = {2012}, author = {Lammert, E and Axnick, J}, title = {Vascular lumen formation.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {2}, number = {4}, pages = {a006619}, pmid = {22474612}, issn = {2157-1422}, mesh = {Animals ; Blood Vessels/anatomy & histology/*embryology/physiology ; Endothelial Cells/*cytology/*metabolism ; Endothelium, Vascular/*physiology ; Humans ; Invertebrates/physiology ; Neoplasms/blood supply ; Neovascularization, Pathologic/physiopathology ; Neovascularization, Physiologic/physiology ; Signal Transduction ; Vertebrates/physiology ; }, abstract = {The vascular system developed early in evolution. It is required in large multicellular organisms for the transport of nutrients, oxygen, and waste products to and from tissues. The vascular system is composed of hollow tubes, which have a high level of complexity in vertebrates. Vasculogenesis describes the de novo formation of blood vessels, e.g., aorta formation in vertebrate embryogenesis. In contrast, angiogenesis is the formation of blood vessels from preexisting ones, e.g., sprouting of intersomitic blood vessels from the aorta. Importantly, the lumen of all blood vessels in vertebrates is lined and formed by endothelial cells. In both vasculogenesis and angiogenesis, lumen formation takes place in a cord of endothelial cells. It involves a complex molecular mechanism composed of endothelial cell repulsion at the cell-cell contacts within the endothelial cell cords, junctional rearrangement, and endothelial cell shape change. As the vascular system also participates in the course of many diseases, such as cancer, stroke, and myocardial infarction, it is important to understand and make use of the molecular mechanisms of blood vessel formation to better understand and manipulate the pathomechanisms involved.}, } @article {pmid22467866, year = {2012}, author = {Shih, W and Yamada, S}, title = {N-cadherin-mediated cell-cell adhesion promotes cell migration in a three-dimensional matrix.}, journal = {Journal of cell science}, volume = {125}, number = {Pt 15}, pages = {3661-3670}, pmid = {22467866}, issn = {1477-9137}, support = {R01 GM094798/GM/NIGMS NIH HHS/United States ; GM094798/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/metabolism ; Animals ; Cadherins/genetics/metabolism/*physiology ; Cell Adhesion/*physiology ; Cell Line ; Cell Line, Transformed ; Cell Movement/*physiology ; Collagen/chemistry ; Cytoskeleton/metabolism ; Dogs ; Epithelial Cells/*cytology ; Epithelial-Mesenchymal Transition/drug effects/physiology ; Gene Knockdown Techniques ; Hepatocyte Growth Factor/pharmacology ; Madin Darby Canine Kidney Cells ; Stress Fibers/metabolism ; alpha Catenin/metabolism ; }, abstract = {Cancer cells that originate from epithelial tissues typically lose epithelial specific cell-cell junctions, but these transformed cells are not devoid of cell-cell adhesion proteins. Using hepatocyte-growth-factor-treated MDCK cells that underwent a complete epithelial-to-mesenchymal transition, we analyzed cell-cell adhesion between these highly invasive transformed epithelial cells in a three-dimensional (3D) collagen matrix. In a 3D matrix, these transformed cells formed elongated multicellular chains, and migrated faster and more persistently than single cells in isolation. In addition, the cell clusters were enriched with stress-fiber-like actin bundles that provided contractile forces. N-cadherin-knockdown cells failed to form cell-cell junctions or migrate, and the expression of the N-cadherin cytoplasmic or extracellular domain partially rescued the knockdown phenotype. By contrast, the expression of N-cadherin-α-catenin chimera rescued the knockdown phenotype, but individual cells within the cell clusters were less mobile. Together, our findings suggest that a dynamic N-cadherin and actin linkage is required for efficient 3D collective migration.}, } @article {pmid22464976, year = {2012}, author = {Okamoto, K and Nakatsukasa, M and Alié, A and Masuda, Y and Agata, K and Funayama, N}, title = {The active stem cell specific expression of sponge Musashi homolog EflMsiA suggests its involvement in maintaining the stem cell state.}, journal = {Mechanisms of development}, volume = {129}, number = {1-4}, pages = {24-37}, doi = {10.1016/j.mod.2012.03.001}, pmid = {22464976}, issn = {1872-6356}, mesh = {Animals ; Cell Cycle Checkpoints ; Cell Differentiation ; Cell Division ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Gene Expression ; Organ Specificity ; Phylogeny ; Porifera/*cytology/genetics/metabolism ; Protein Transport ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins/genetics/*metabolism ; Stem Cells/*physiology ; }, abstract = {A hallmark of stem cells is the ability to sustainably generate stem cells themselves (self-renew) as well as differentiated cells. Although a full understanding of this ability will require clarifying underlying the primordial molecular and cellular mechanisms, how stem cells maintain their stem state and their population in the evolutionarily oldest extant multicellular organisms, sponges, is poorly understood. Here, we report the identification of the first stem cell-specific gene in demosponges, a homolog of Musashi (an evolutionarily conserved RNA binding protein that regulates the stem cell state in various organisms). EflMsiA, a Musashi paralog, is specifically expressed in stem cells (archeocytes) in the freshwater sponge Ephydatia fluviatilis. EflMsiA protein is localized predominantly in the nucleus, with a small fraction in the cytoplasm, in archeocytes. When archeocytes enter M-phase, EflMsiA protein diffuses into the cytoplasm, probably because of the breakdown of the nuclear membrane. In the present study, the existence of two types of M-phase archeocytes [(M)-archeocytes] was revealed by a precise analysis of the expression levels of EflMsiA mRNA and protein. In Type I (M)-archeocytes, presumably archeocytes undergoing self-renewal, the expression levels of EflMsiA mRNA and protein were high. In Type II (M)-archeocytes, presumably archeocytes committed to differentiate (committed archeocytes), the expression levels of EflMsiA mRNA and protein were about 60% and 30% lower than those in Type I (M)-archeocytes. From these results, archeocytes can be molecularly defined for the first time as EflMsiA-mRNA-expressing cells. Furthermore, these findings shed light on the mode of cell division of archeocytes and suggest that archeocytes divide symmetrically for both self-renewal and differentiation.}, } @article {pmid22458243, year = {2012}, author = {Denardi, JD and Oliveira, DM and Paiva, EA}, title = {Glandular trichomes in Connarus suberosus (Connaraceae): distribution, structural organization and probable functions.}, journal = {Revista de biologia tropical}, volume = {60}, number = {1}, pages = {505-513}, doi = {10.15517/rbt.v60i1.2785}, pmid = {22458243}, issn = {0034-7744}, mesh = {Brazil ; Connaraceae/chemistry/classification/*ultrastructure ; Microscopy, Electron ; }, abstract = {Connarus suberosus is a typical species of the Brazilian Cerrado biome, and its inflorescences and young vegetative branches are densely covered by dendritic trichomes. The objective of this study was to report the occurrence of a previously undescribed glandular trichome of this species. The localization, origin and structure of these trichomes were investigated under light, transmission and scanning electron microscopy. Collections were made throughout the year, from five adult specimens of Connarus suberosus near Botucatu, São Paulo, Brazil, including vegetative and reproductive apices, leaves and fruits in different developmental stages, as well as floral buds and flowers at anthesis. Glandular trichomes (GTs) occurred on vegetative and reproductive organs during their juvenile stages. The GTs consisted of a uniseriate, multicellular peduncle, whose cells contain phenolic compounds, as well as a multicellular glandular portion that accumulates lipids. The glandular cell has thin wall, dense cytoplasm (with many mitochondria, plastids and dictyosomes), and a large nucleus with a visible nucleolus. The starch present in the plastids was hydrolyzed during the synthesis phase, reducing the density of the plastid stroma. Some plastids were fused to vacuoles, and some evidence suggested the conversion of plastids into vacuoles. During the final activity stages of the GTs, a darkening of the protoplasm was observed in some of the glandular cells, as a programmed cell death; afterwards, became caducous. The GTs in C. suberosus had a temporal restriction, being limited to the juvenile phase of the organs. Their presence on the exposed surfaces of developing organs and the chemical nature of the reserve products, suggest that these structures are food bodies. Field observations and detailed studies of plant-environment interactions, as well as chemical analysis of the reserve compounds, are still necessary to confirm the role of these GTs as feeding rewards.}, } @article {pmid22456498, year = {2012}, author = {Nussbaum, JC and Locksley, RM}, title = {Infectious (Non)tolerance--frustrated commensalism gone awry?.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {4}, number = {5}, pages = {}, pmid = {22456498}, issn = {1943-0264}, support = {R01 AI030663/AI/NIAID NIH HHS/United States ; R37 AI026918/AI/NIAID NIH HHS/United States ; T32 AI007641/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Communicable Diseases/*microbiology ; Host-Pathogen Interactions/*immunology/physiology ; Humans ; Immune Tolerance/*immunology ; Inflammation/*microbiology ; Mice ; *Models, Biological ; Signal Transduction/*immunology ; Symbiosis/*immunology/physiology ; }, abstract = {Despite advances in medicine, infectious diseases remain major causes of death and disability worldwide. Acute or chronic infectious agents mediate host tissue damage and cause a spectrum of disease as diverse as overwhelming sepsis and shock within hours to persistent tissue inflammation causing organ failure or even cancer over years. Although pathogen exposure can cause disease via host-derived inflammation, pathogens share recognized elements with harmless human commensals. Mouse models and organisms with simpler flora are revealing the dialogue between multicellular hosts and commensal flora. In some instances the persistent inflammation associated with pathogens can be interpreted within a framework of frustrated commensalism in which the host and pathogen cannot complete the requisite dialogue that establishes homeostasis. In contrast, coevolved commensals interact cooperatively with the host immune system, resulting in immunotolerance. Attempts to more thoroughly understand the molecular nature of the dialogue may uncover novel approaches to the control of inflammation and tissue damage.}, } @article {pmid22453942, year = {2012}, author = {Mackrill, JJ}, title = {Ryanodine receptor calcium release channels: an evolutionary perspective.}, journal = {Advances in experimental medicine and biology}, volume = {740}, number = {}, pages = {159-182}, doi = {10.1007/978-94-007-2888-2_7}, pmid = {22453942}, issn = {0065-2598}, mesh = {Animals ; Calcium/metabolism ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Humans ; Protein Structure, Tertiary ; Ryanodine Receptor Calcium Release Channel/chemistry/genetics/*physiology ; }, abstract = {Ryanodine receptors (RyRs), along with the related inositol 1,4,5-trisphosphate receptors (IP(3)Rs), mediate the release of Ca(2+) from intracellular organelles of eukaryotes. As discussed in other chapters, such increases in intracellular Ca(2+) levels act a fundamental second messenger, regulating a diverse array of cellular processes. For over two decades, it has been reported that vertebrates express multiple RYR genes, whereas non-vertebrate multicellular organisms possess a single homologue within their genomes. Recently, the existence of RyR-like channels in unicellular organisms has also been reported. This chapter exploits recent expansions in available genome data to generate an overview of the expression of RyR-like genes in organisms representing a broad range of viral, archaeal, bacterial and eukaryotic taxa. Analyses of the multidomain structures and phylogenetic relationships of these proteins has lead to a model in which, early during eukaryotic evolution, IP(3)R-like ancestral Ca(2+) release channels were converted to RyR proteins via the addition of promiscuous protein domains, possibly via horizontal gene transfer mechanisms.}, } @article {pmid22451943, year = {2012}, author = {Sharp, NP and Agrawal, AF}, title = {Evidence for elevated mutation rates in low-quality genotypes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {16}, pages = {6142-6146}, pmid = {22451943}, issn = {1091-6490}, mesh = {Adaptation, Physiological/genetics ; Alleles ; Animals ; Chromosomes, Insect/*genetics ; Crosses, Genetic ; Drosophila melanogaster/*genetics ; Evolution, Molecular ; Female ; Genotype ; Humans ; Male ; *Models, Genetic ; *Mutation Rate ; Stress, Physiological/genetics ; }, abstract = {The deleterious mutation rate plays a key role in a number of important topics in biology, from mating system evolution to human health. Despite this broad significance, the nature and causes of variation in mutation rate are poorly understood, especially in multicellular organisms. We test whether genetic quality, the presence or absence of deleterious alleles, affects the mutation rate in Drosophila melanogaster by using a modified mutation accumulation approach. We find evidence that genotypes constructed to carry deleterious "treatment" alleles on one chromosome during mutation accumulation experience an elevated mutation rate on a different chromosome. Further, this elevation is correlated with the effect of the treatment alleles on phenotypic condition, measured as body mass. Treatment alleles that reduce mass by 10% cause a doubling in the rate of mutational decline. Our results show that mutation rates are sensitive to genetic stress, such that individuals with low-quality genotypes will produce offspring of even lower genetic quality, in a mutational positive feedback loop. This type of variation in mutation rate is expected to alter a variety of predictions based on mutation load theory and accelerate adaptation to new environments. Positive mutational feedback could affect human health by increasing the rate of germline mutation, and possibly somatic mutation, in individuals of poor health because of genetic or environmental stress.}, } @article {pmid22449041, year = {2012}, author = {Oikawa, A and Saito, K}, title = {Metabolite analyses of single cells.}, journal = {The Plant journal : for cell and molecular biology}, volume = {70}, number = {1}, pages = {30-38}, doi = {10.1111/j.1365-313X.2012.04967.x}, pmid = {22449041}, issn = {1365-313X}, mesh = {Mass Spectrometry ; Metabolomics/*methods ; Plant Cells/*metabolism ; Plants/*metabolism ; Single-Cell Analysis/*methods ; }, abstract = {Single-cell analysis is a promising method for understanding not only cellular physiology but also biological mechanisms of multicellular organisms. Although neighboring cells in multicellular organisms originate from the same genomic information, different circumstances around cells or epigenetic differences have different influences on each cell, leading to differing expression of genes, and thus differing levels and dynamics of metabolites, in single cells. However, single-cell analysis is a tough challenge, even with recent technologies, because of the small size of single cells. Unlike genes, metabolites cannot be amplified, and therefore metabolite analysis is another issue. To analyze such a tiny quantity of metabolites in a single cell, various techniques have been tried and developed. Especially in mass spectrometry, marked improvements in both detection sensitivity and ionization techniques have opened up the challenge for the analysis of metabolites in single cells. In this review, we discuss the method for metabolite detection at the level of single cells and recent advancements in technology.}, } @article {pmid22442339, year = {2012}, author = {Schönenberger, J and von Balthazar, M and Takahashi, M and Xiao, X and Crane, PR and Herendeen, PS}, title = {Glandulocalyx upatoiensis, a fossil flower of Ericales (Actinidiaceae/Clethraceae) from the Late Cretaceous (Santonian) of Georgia, USA.}, journal = {Annals of botany}, volume = {109}, number = {5}, pages = {921-936}, pmid = {22442339}, issn = {1095-8290}, mesh = {Actinidiaceae/*anatomy & histology/genetics ; *Biological Evolution ; Clethraceae/*anatomy & histology/genetics ; Flowers/*anatomy & histology/genetics/ultrastructure ; Fossils ; Fruit/anatomy & histology/genetics ; Georgia ; Magnoliopsida/*anatomy & histology/genetics ; Microscopy, Electron, Scanning ; Phylogeny ; Seeds/anatomy & histology/genetics ; }, abstract = {BACKGROUND AND AIMS: Ericales are a major group of extant asterid angiosperms that are well represented in the Late Cretaceous fossil record, mainly by flowers, fruits and seeds. Exceptionally well preserved fossil flowers, here described as Glandulocalyx upatoiensis gen. & sp. nov., from the Santonian of Georgia, USA, yield new detailed evidence of floral structure in one of these early members of Ericales and provide a secure basis for comparison with extant taxa.

METHODS: The floral structure of several fossil specimens was studied by scanning electron microscopy (SEM), light microscopy of microtome thin sections and synchrotron-radiation X-ray tomographic microscopy (SRXTM). For direct comparisons with flowers of extant Ericales, selected floral features of Actinidiaceae and Clethraceae were studied with SEM.

KEY RESULTS: Flowers of G. upatoiensis have five sepals with quincuncial aestivation, five free petals with quincuncial aestivation, 20-28 stamens arranged in a single series, extrorse anther orientation in the bud, ventral anther attachment and a tricarpellate, syncarpous ovary with three free styles and numerous small ovules on axile, protruding-diffuse and pendant placentae. The calyx is characterized by a conspicuous indumentum of large, densely arranged, multicellular and possibly glandular trichomes.

CONCLUSIONS: Comparison with extant taxa provides clear evidence for a relationship with core Ericales comprised of the extant families Actinidiaceae, Roridulaceae, Sarraceniaceae, Clethraceae, Cyrillaceae and Ericaceae. Within this group, the most marked similarities are with extant Actinidiaceae and, to a lesser degree, with Clethraceae. More detailed analyses of the relationships of Glandulocalyx and other Ericales from the Late Cretaceous will require an improved understanding of the morphological features that diagnose particular extant groups defined on the basis of molecular data.}, } @article {pmid22438907, year = {2012}, author = {Koch, BJ and Ryan, JF and Baxevanis, AD}, title = {The diversification of the LIM superclass at the base of the metazoa increased subcellular complexity and promoted multicellular specialization.}, journal = {PloS one}, volume = {7}, number = {3}, pages = {e33261}, pmid = {22438907}, issn = {1932-6203}, support = {//Intramural NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Bayes Theorem ; Evolution, Molecular ; Genetic Speciation ; Genetic Variation ; Humans ; LIM Domain Proteins/chemistry/*classification/*genetics ; Likelihood Functions ; Models, Genetic ; Molecular Sequence Data ; Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {BACKGROUND: Throughout evolution, the LIM domain has been deployed in many different domain configurations, which has led to the formation of a large and distinct group of proteins. LIM proteins are involved in relaying stimuli received at the cell surface to the nucleus in order to regulate cell structure, motility, and division. Despite their fundamental roles in cellular processes and human disease, little is known about the evolution of the LIM superclass.

RESULTS: We have identified and characterized all known LIM domain-containing proteins in six metazoans and three non-metazoans. In addition, we performed a phylogenetic analysis on all LIM domains and, in the process, have identified a number of novel non-LIM domains and motifs in each of these proteins. Based on these results, we have formalized a classification system for LIM proteins, provided reasonable timing for class and family origin events; and identified lineage-specific loss events. Our analysis is the first detailed description of the full set of LIM proteins from the non-bilaterian species examined in this study.

CONCLUSION: Six of the 14 LIM classes originated in the stem lineage of the Metazoa. The expansion of the LIM superclass at the base of the Metazoa undoubtedly contributed to the increase in subcellular complexity required for the transition from a unicellular to multicellular lifestyle and, as such, was a critically important event in the history of animal multicellularity.}, } @article {pmid22434426, year = {2012}, author = {Chang, GS and Noegel, AA and Mavrich, TN and Müller, R and Tomsho, L and Ward, E and Felder, M and Jiang, C and Eichinger, L and Glöckner, G and Schuster, SC and Pugh, BF}, title = {Unusual combinatorial involvement of poly-A/T tracts in organizing genes and chromatin in Dictyostelium.}, journal = {Genome research}, volume = {22}, number = {6}, pages = {1098-1106}, pmid = {22434426}, issn = {1549-5469}, support = {R01 HG004160/HG/NHGRI NIH HHS/United States ; R56 HG004160/HG/NHGRI NIH HHS/United States ; HG004160/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Chromatin/*genetics ; Dictyostelium/*genetics ; Genes ; Nucleosomes/*genetics ; Phylogeny ; Poly A/*genetics ; Poly T/*genetics ; Promoter Regions, Genetic ; RNA Polymerase II/genetics ; TATA Box/genetics ; Transcription Factors/genetics ; }, abstract = {Dictyostelium discoideum is an amoebozoa that exists in both a free-living unicellular and a multicellular form. It is situated in a deep branch in the evolutionary tree and is particularly noteworthy in having a very A/T-rich genome. Dictyostelium provides an ideal system to examine the extreme to which nucleotide bias may be employed in organizing promoters, genes, and nucleosomes across a genome. We find that Dictyostelium genes are demarcated precisely at their 5' ends by poly-T tracts and precisely at their 3' ends by poly-A tracts. These tracts are also associated with nucleosome-free regions and are embedded with precisely positioned TATA boxes. Homo- and heteropolymeric tracts of A and T demarcate nucleosome border regions. Together, these findings reveal the presence of a variety of functionally distinct polymeric A/T elements. Strikingly, Dictyostelium chromatin may be organized in di-nucleosome units but is otherwise organized as in animals. This includes a +1 nucleosome in a position that predicts the presence of a paused RNA polymerase II. Indeed, we find a strong phylogenetic relationship between the presence of the NELF pausing factor and positioning of the +1 nucleosome. Pausing and +1 nucleosome positioning may have coevolved in animals.}, } @article {pmid22427962, year = {2012}, author = {Edlund, A and Ek, K and Breitholtz, M and Gorokhova, E}, title = {Antibiotic-induced change of bacterial communities associated with the copepod Nitocra spinipes.}, journal = {PloS one}, volume = {7}, number = {3}, pages = {e33107}, pmid = {22427962}, issn = {1932-6203}, mesh = {Animals ; Anti-Bacterial Agents/*toxicity ; Bacteria/*drug effects/genetics ; Base Sequence ; *Biodiversity ; Chromatography, Liquid ; Cloning, Molecular ; Copepoda/*drug effects/growth & development/*microbiology ; DNA Primers/genetics ; Likelihood Functions ; Models, Genetic ; Molecular Sequence Data ; Oceans and Seas ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Species Specificity ; Sweden ; *Symbiosis ; Tandem Mass Spectrometry ; Water Pollutants, Chemical/*toxicity ; }, abstract = {Environmental pressures, such as physical factors, diet and contaminants may affect interactions between microbial symbionts and their multicellular hosts. Despite obvious relevance, effects of antimicrobial contaminants on host-symbiont relations in non-target aquatic organisms are largely unknown. We show that exposure to antibiotics had negative effects on survival and juvenile development of the copepod Nitocra spinipes and caused significant alterations in copepod-associated bacterial communities. The significant positive correlations between indices of copepod development and bacterial diversity indicate that disruption of the microflora was likely to be an important factor behind retarded juvenile development in the experimental animals. Moreover, as evidenced by ribotype distribution in the bacterial clone libraries, the exposure to antibiotics caused a shift in dominance from Betaproteobacteria to Cardinium bacteria; the latter have been shown to cause reproductive manipulations in various terrestrial arthropods. Thus, in addition to providing evidence that the antibiotic-induced perturbation of the microbial community associates with reductions in fitness-related traits of the host, this study is the first record of a copepod serving as a host for endosymbiotic Cardinium. Taken together, our results suggest that (1) antimicrobial substances and possibly other stressors can affect micobiome and symbiont-mediated interactions in copepods and other hosts, and (2) Cardinium endosymbionts may occur in other copepods and affect reproduction of their hosts.}, } @article {pmid22426243, year = {2012}, author = {Buttigieg, J and Nurse, CA}, title = {Methodologies for studying peripheral O2 chemosensing: past, present, and future.}, journal = {Respiratory physiology & neurobiology}, volume = {181}, number = {2}, pages = {194-201}, doi = {10.1016/j.resp.2012.03.001}, pmid = {22426243}, issn = {1878-1519}, mesh = {Animals ; Chromatography, High Pressure Liquid/methods ; Dogs ; Electrochemical Techniques ; Electrophysiological Phenomena ; Humans ; Mice ; Models, Animal ; *Oxidative Phosphorylation ; Oxygen/analysis/*metabolism ; Patch-Clamp Techniques ; Rabbits ; Rats ; }, abstract = {The reduction of molecular oxygen in individual cells during the process of oxidative phosphorylation is central to oxidative metabolism and bioenergetic homeostasis. As such, any insufficiency in molecular oxygen availability represents a severe threat to sustained life. Thus, as with other similar multicellular organisms, the human body has evolved various peripheral chemosensory pathways that play a key role in sampling arterial PO2 values and initiating corrective reflex responses so as to maintain homeostasis. Research on these peripheral chemosensors can trace their origins to the cross circulation studies of Corneille Heymans in the early 20th century. Since then, it has become increasingly apparent that defects in these chemosensory pathways play a key role in various pathological conditions, e.g. Sudden Infant Death Syndrome (SIDS), and therefore an understanding of the underlying mechanisms is of critical importance. This review aims to discuss the advantages and disadvantages of the various experimental models employed in studying the mechanisms by which acute peripheral chemosensing occurs.}, } @article {pmid22411854, year = {2012}, author = {Moran, Y and Fredman, D and Szczesny, P and Grynberg, M and Technau, U}, title = {Recurrent horizontal transfer of bacterial toxin genes to eukaryotes.}, journal = {Molecular biology and evolution}, volume = {29}, number = {9}, pages = {2223-2230}, pmid = {22411854}, issn = {1537-1719}, support = {P 24858/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Amino Acid Sequence ; Animals ; Bacterial Toxins/chemistry/*genetics/metabolism ; Cnidaria/genetics/metabolism ; Eukaryota/*genetics/metabolism ; Evolution, Molecular ; Gene Expression ; *Gene Transfer, Horizontal ; Molecular Sequence Data ; Phylogeny ; Pore Forming Cytotoxic Proteins/chemistry/genetics/metabolism ; Sequence Alignment ; }, abstract = {In this work, we report likely recurrent horizontal (lateral) gene transfer events of genes encoding pore-forming toxins of the aerolysin family between species belonging to different kingdoms of life. Clustering based on pairwise similarity and phylogenetic analysis revealed several distinct aerolysin sequence groups, each containing proteins from multiple kingdoms of life. These results strongly support at least six independent transfer events between distantly related phyla in the evolutionary history of one protein family and discount selective retention of ancestral genes as a plausible explanation for this patchy phylogenetic distribution. We discuss the possible roles of these proteins and show evidence for a convergent new function in two extant species. We hypothesize that certain gene families are more likely to be maintained following horizontal gene transfer from commensal or pathogenic organism to its host if they 1) can function alone; and 2) are immediately beneficial for the ecology of the organism, as in the case of pore-forming toxins which can be utilized in multicellular organisms for defense and predation.}, } @article {pmid22409430, year = {2012}, author = {Tian, HF and Feng, JM and Wen, JF}, title = {The evolution of cardiolipin biosynthesis and maturation pathways and its implications for the evolution of eukaryotes.}, journal = {BMC evolutionary biology}, volume = {12}, number = {}, pages = {32}, pmid = {22409430}, issn = {1471-2148}, mesh = {Base Sequence ; Bayes Theorem ; Biosynthetic Pathways/*physiology ; Cardiolipins/*biosynthesis/*metabolism ; Eukaryota/*enzymology/genetics/metabolism ; *Evolution, Molecular ; Likelihood Functions ; Membrane Proteins/metabolism/*physiology ; Models, Genetic ; Molecular Sequence Data ; Phospholipases A2, Calcium-Independent/genetics/metabolism ; *Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; Transferases (Other Substituted Phosphate Groups)/metabolism/*physiology ; }, abstract = {BACKGROUND: Cardiolipin (CL) is an important component in mitochondrial inner and bacterial membranes. Its appearance in these two biomembranes has been considered as evidence of the endosymbiotic origin of mitochondria. But CL was reported to be synthesized through two distinct enzymes--CLS_cap and CLS_pld in eukaryotes and bacteria. Therefore, how the CL biosynthesis pathway evolved is an interesting question.

RESULTS: Phylogenetic distribution investigation of CL synthase (CLS) showed: most bacteria have CLS_pld pathway, but in partial bacteria including proteobacteria and actinobacteria CLS_cap pathway has already appeared; in eukaryotes, Supergroup Opisthokonta and Archaeplastida, and Subgroup Stramenopiles, which all contain multicellular organisms, possess CLS_cap pathway, while Supergroup Amoebozoa and Excavata and Subgroup Alveolata, which all consist exclusively of unicellular eukaryotes, bear CLS_pld pathway; amitochondriate protists in any supergroups have neither. Phylogenetic analysis indicated the CLS_cap in eukaryotes have the closest relationship with those of alpha proteobacteria, while the CLS_pld in eukaryotes share a common ancestor but have no close correlation with those of any particular bacteria.

CONCLUSIONS: The first eukaryote common ancestor (FECA) inherited the CLS_pld from its bacterial ancestor (e. g. the bacterial partner according to any of the hypotheses about eukaryote evolution); later, when the FECA evolved into the last eukaryote common ancestor (LECA), the endosymbiotic mitochondria (alpha proteobacteria) brought in CLS_cap, and then in some LECA individuals the CLS_cap substituted the CLS_pld, and these LECAs would evolve into the protist lineages from which multicellular eukaryotes could arise, while in the other LECAs the CLS_pld was retained and the CLS_cap was lost, and these LECAs would evolve into the protist lineages possessing CLS_pld. Besides, our work indicated CL maturation pathway arose after the emergence of eukaryotes probably through mechanisms such as duplication of other genes, and gene duplication and loss occurred frequently at different lineage levels, increasing the pathway diversity probably to fit the complicated cellular process in various cells. Our work also implies the classification putting Stramenopiles and Alveolata together to form Chromalveolata may be unreasonable; the absence of CL synthesis and maturation pathways in amitochondriate protists is most probably due to secondary loss.}, } @article {pmid22399377, year = {2012}, author = {Muñoz-Pinedo, C}, title = {Signaling pathways that regulate life and cell death: evolution of apoptosis in the context of self-defense.}, journal = {Advances in experimental medicine and biology}, volume = {738}, number = {}, pages = {124-143}, doi = {10.1007/978-1-4614-1680-7_8}, pmid = {22399377}, issn = {0065-2598}, support = {08-0621/AICR_/Worldwide Cancer Research/United Kingdom ; }, mesh = {Animals ; Apoptosis/*immunology ; *Biological Evolution ; Granzymes/immunology ; Humans ; Inhibitor of Apoptosis Proteins/immunology ; Mitochondria/immunology ; Receptors, Death Domain/immunology ; Signal Transduction/*immunology ; Stress, Physiological/*immunology ; }, abstract = {Programmed Cell Death is essential for the life cycle of many organisms. Cell death in multicellular organisms can occur as a consequence of massive damage (necrosis) or in a controlled form, through engagement of diverse biochemical programs. The best well known form of programmed cell death is apoptosis. Apoptosis occurs in animals as a consequence of a variety of stimuli including stress and social signals and it plays essential roles in morphogenesis and immune defense. The machinery of apoptosis is well conserved among animals and it is composed of caspases (the proteases which execute cell death), adapter proteins (caspase activators), Bcl-2 family proteins and Inhibitor of Apoptosis Proteins (IAPs). We will describe in this chapter the main apoptotic pathways in animals: the extrinsic (death receptor-mediated), the intrinsic/mitochondrial and the Granzyme B pathway. Other forms of non-apoptotic Programmed Cell Death which occur in animals will also be discussed. We will summarize the current knowledge about apoptotic-like and other forms of cell death in other organisms such as plants and protists.Additionally, we will discuss the hypothesis that apoptosis originated as part of a host defense mechanism. We will explore the similarities between the protein complexes which mediate apoptosis (apoptosomes) and complexes involved in immunity: inflammasomes. Additional functions of apoptotic proteins related to immune function will be summarized, in an effort to explore the evolutionary origins of cell death.}, } @article {pmid22399372, year = {2012}, author = {Misevic, GN and Misevic, N and Popescu, O}, title = {Glyconectin glycans as the self-assembling nano-molecular-velcrosystem mediating self-nonself recognition and adhesion implicated in evolution of multicellularity.}, journal = {Advances in experimental medicine and biology}, volume = {738}, number = {}, pages = {31-45}, doi = {10.1007/978-1-4614-1680-7_3}, pmid = {22399372}, issn = {0065-2598}, mesh = {Animals ; Cell Adhesion/physiology ; *Evolution, Molecular ; Glycoproteins/chemistry/genetics/*metabolism ; Peptidoglycan/chemistry/genetics/*metabolism ; Porifera/*physiology ; }, abstract = {The goal of this chapter is to make a specific contribution about glyconectin glycan as the self-assembling nano-molecular-velcro system mediating initial steps of self-nonself recognition and cell adhesion in Porifera, the first descendants of the most simple primordial multicellular organisms. Two original findings will be described: (i) Velcro like concept based on highly polyvalent and specific intermolecular glycan to glycan associations with extremely low affinity of the single binding site and (ii) novel structures of the large and newly emerging family of glyconectin like glycan molecules. The emphasis will be put on the interdisciplinary approach for studying structure to function relationship at the different size scale levels by combining the knowledge and technologies (instrumentation and methods) of physics, chemistry, biology and mathematics. Applying such strategy which is crossing the boundaries of different science disciplines enabled us to develop a new Atomic Force Microscopy (AFM) based nano-bio-technology and perform the first quantitative measurements of intermolecular binding forces at the single molecular level under physiological conditions. We propose that nano-velcro systems of the glyconectin glycans, which are the constituents on the cell surface that are the most exposed to the environment, were responsible for the molecular self-nonself recognition and adhesion processes that underpinned the emergence of multicellular life forms.}, } @article {pmid22399371, year = {2012}, author = {Nedelcu, AM}, title = {The evolution of self during the transition to multicellularity.}, journal = {Advances in experimental medicine and biology}, volume = {738}, number = {}, pages = {14-30}, doi = {10.1007/978-1-4614-1680-7_2}, pmid = {22399371}, issn = {0065-2598}, mesh = {*Biological Evolution ; Chlorophyta/*physiology ; }, abstract = {The notion of ' self' is intrinsically linked to the concepts of identity and individuality. During evolutionary transitions in individuality-such as, for instance, during the origin of the first cell, the origin of the eukaryotic cell and the origin of multicellular individuals-new kinds of individuals emerged from the interaction of previously independent entities. The question discussed here is: How can new types of individuals with qualities that cannot be reduced to the properties of their parts be created at a higher level? This question is addressed in the context of the transition to multicellularity and using the volvocine green algae-a group of closely related unicellular and multicellular species with various degrees of physiological and reproductive unity-as a model system. In this chapter, we review our framework to addressing the evolution of individuality during the transition to multicellularity, focusing on the reorganization of general life-traits and cellular processes and the cooption of environmentally-induced responses.}, } @article {pmid22394375, year = {2012}, author = {Dittami, SM and Gravot, A and Goulitquer, S and Rousvoal, S and Peters, AF and Bouchereau, A and Boyen, C and Tonon, T}, title = {Towards deciphering dynamic changes and evolutionary mechanisms involved in the adaptation to low salinities in Ectocarpus (brown algae).}, journal = {The Plant journal : for cell and molecular biology}, volume = {71}, number = {3}, pages = {366-377}, doi = {10.1111/j.1365-313X.2012.04982.x}, pmid = {22394375}, issn = {1365-313X}, mesh = {Amino Acids/metabolism ; Anions/metabolism ; Base Sequence ; *Biological Evolution ; Carbohydrate Metabolism ; Cations/metabolism ; Ecosystem ; Fatty Acids, Omega-3/metabolism ; Fresh Water ; Gene Expression Profiling ; Genome, Plant/genetics ; Metabolome/*physiology ; Molecular Sequence Data ; Nitrogen/metabolism ; Oligonucleotide Array Sequence Analysis ; Phaeophyta/classification/genetics/*physiology ; Phylogeny ; Salinity ; Salt Tolerance/genetics/*physiology ; Sequence Analysis, DNA ; Transcriptome/*physiology ; }, abstract = {Colonizations of freshwater by marine species are rare events, and little information is known about the underlying mechanisms. Brown algae are an independent lineage of photosynthetic and multicellular organisms from which few species inhabit freshwater. As a marine alga that is also found in freshwater, Ectocarpus is of particular interest for studying the transition between these habitats. To gain insights into mechanisms of the transition, we examined salinity tolerance and adaptations to low salinities in a freshwater strain of Ectocarpus on physiological and molecular levels. We show that this isolate belongs to a widely distributed and highly stress-resistant clade, and differed from the genome-sequenced marine strain in its tolerance of low salinities. It also exhibited profound, but reversible, morphological, physiological, and transcriptomic changes when transferred to seawater. Although gene expression profiles were similar in both strains under identical conditions, metabolite and ion profiles differed strongly, the freshwater strain exhibiting e.g. higher cellular contents of amino acids and nitrate, higher contents of n-3 fatty acids, and lower intracellular mannitol and sodium concentrations. Moreover, several stress markers were noted in the freshwater isolate in seawater. This finding suggests that, while high stress tolerance and plasticity may be prerequisites for the colonization of freshwater, genomic alterations have occurred that produced permanent changes in the metabolite profiles to stabilize the transition.}, } @article {pmid22374462, year = {2012}, author = {Kailayangiri, S and Altvater, B and Meltzer, J and Pscherer, S and Luecke, A and Dierkes, C and Titze, U and Leuchte, K and Landmeier, S and Hotfilder, M and Dirksen, U and Hardes, J and Gosheger, G and Juergens, H and Rossig, C}, title = {The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting.}, journal = {British journal of cancer}, volume = {106}, number = {6}, pages = {1123-1133}, pmid = {22374462}, issn = {1532-1827}, mesh = {Adolescent ; Adult ; Animals ; Antigens, Surface/immunology/metabolism ; Bone Neoplasms/immunology/*metabolism/therapy ; Cell Line, Tumor ; Cell Proliferation ; Child ; Coculture Techniques ; Cytotoxicity, Immunologic ; Female ; Gangliosides/immunology/*metabolism ; Granzymes/metabolism ; Humans ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Transplantation ; Receptors, Antigen, T-Cell/biosynthesis/metabolism ; Recombinant Fusion Proteins/biosynthesis/metabolism ; Sarcoma, Ewing/immunology/*metabolism/therapy ; Single-Chain Antibodies/biosynthesis/metabolism ; Spheroids, Cellular/immunology ; T-Lymphocytes/immunology/metabolism/*transplantation ; Young Adult ; }, abstract = {BACKGROUND: Novel treatment strategies are needed to cure disseminated Ewing sarcoma. Primitive neuroectodermal features and a mesenchymal stem cell origin are both compatible with aberrant expression of the ganglioside antigen G(D2) and led us to explore G(D2) immune targeting in this cancer.

METHODS: We investigated G(D2) expression in Ewing sarcoma by immunofluorescence staining. We then assessed the antitumour activity of T cells expressing a chimeric antigen receptor specific for G(D2) against Ewing sarcoma in vitro and in vivo.

RESULTS: Surface G(D2) was detected in 10 out of 10 Ewing sarcoma cell lines and 3 out of 3 primary cell cultures. Moreover, diagnostic biopsies from 12 of 14 patients had uniform G(D2) expression. T cells specifically modified to express the G(D2)-specific chimeric receptor 14. G2a-28ζ efficiently interacted with Ewing sarcoma cells, resulting in antigen-specific secretion of cytokines. Moreover, chimeric receptor gene-modified T cells from healthy donors and from a patient exerted potent, G(D2)-specific cytolytic responses to allogeneic and autologous Ewing sarcoma, including tumour cells grown as multicellular, anchorage-independent spheres. G(D2)-specific T cells further had activity against Ewing sarcoma xenografts.

CONCLUSION: G(D2) surface expression is a characteristic of Ewing sarcomas and provides a suitable target antigen for immunotherapeutic strategies to eradicate micrometastatic cells and prevent relapse in high-risk disease.}, } @article {pmid22363744, year = {2012}, author = {Pehl, MJ and Jamieson, WD and Kong, K and Forbester, JL and Fredendall, RJ and Gregory, GA and McFarland, JE and Healy, JM and Orwin, PM}, title = {Genes that influence swarming motility and biofilm formation in Variovorax paradoxus EPS.}, journal = {PloS one}, volume = {7}, number = {2}, pages = {e31832}, pmid = {22363744}, issn = {1932-6203}, support = {R15 GM090242/GM/NIGMS NIH HHS/United States ; S06 GM073842/GM/NIGMS NIH HHS/United States ; R15 GM090242-01/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Bacterial Proteins/genetics/metabolism ; Biofilms/*growth & development ; Biological Assay ; Biopolymers/*metabolism ; Catalytic Domain ; Cell Membrane/metabolism ; Colony Count, Microbial ; Comamonadaceae/*genetics/growth & development/*physiology ; Conserved Sequence/genetics ; Extracellular Space/*metabolism ; Gene Expression Regulation, Bacterial ; Gene Transfer, Horizontal/genetics ; Genes, Bacterial/*genetics ; Genetic Complementation Test ; Genetic Testing ; Molecular Sequence Data ; Movement ; Mutation/genetics ; Nucleotides/genetics ; Phylogeny ; Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Variovorax paradoxus is an aerobic soil bacterium associated with important biodegradative processes in nature. We use V. paradoxus EPS to study multicellular behaviors on surfaces.

METHODOLOGY: We recovered flanking sequence from 123 clones in a Tn5 mutant library, with insertions in 29 different genes, selected based on observed surface behavior phenotypes. We identified three genes, Varpa_4665, Varpa_4680, and Varpa_5900, for further examination. These genes were cloned into pBBR1MCS2 and used to complement the insertion mutants. We also analyzed expression of Varpa_4680 and Varpa_5900 under different growth conditions by qPCR.

RESULTS: The 29 genes we identified had diverse predicted functions, many in exopolysaccharide synthesis. Varpa_4680, the most commonly recovered insertion site, encodes a putative N-acetyl-L-fucosamine transferase similar to WbuB. Expression of this gene in trans complemented the mutant fully. Several unique insertions were identified in Varpa_5900, which is one of three predicted pilY1 homologs in the EPS genome. No insertions in the two other putative pilY1 homologs present in the genome were identified. Expression of Varpa_5900 altered the structure of the wild type swarm, as did disruption of the chromosomal gene. The swarming phenotype was complemented by expression of Varpa_5900 from a plasmid, but biofilm formation was not restored. Both Varpa_4680 and Varpa_5900 transcripts were downregulated in biofilms and upregulated during swarming when compared to log phase culture. We identified a putative two component system (Varpa_4664-4665) encoding a response regulator (shkR) and a sensor histidine kinase (shkS), respectively. Biofilm formation increased and swarming was strongly delayed in the Varpa_4665 (shkS) mutant. Complementation of shkS restored the biofilm phenotype but swarming was still delayed. Expression of shkR in trans suppressed biofilm formation in either genetic background, and partially restored swarming in the mutant.

CONCLUSIONS: The data presented here point to complex regulation of these surface behaviors.}, } @article {pmid22360486, year = {2012}, author = {Makepeace, BL and Martin, C and Turner, JD and Specht, S}, title = {Granulocytes in helminth infection -- who is calling the shots?.}, journal = {Current medicinal chemistry}, volume = {19}, number = {10}, pages = {1567-1586}, pmid = {22360486}, issn = {1875-533X}, support = {242131//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Granulocytes/*immunology/*parasitology ; Helminthiasis/*immunology/parasitology ; Helminths/*immunology ; *Host-Parasite Interactions ; Humans ; Intestinal Diseases, Parasitic/*immunology/parasitology ; }, abstract = {Helminths are parasitic organisms that can be broadly described as "worms" due to their elongated body plan, but which otherwise differ in shape, development, migratory routes and the predilection site of the adults and larvae. They are divided into three major groups: trematodes (flukes), which are leaf-shaped, hermaphroditic (except for blood flukes) flatworms with oral and ventral suckers; cestodes (tapeworms), which are segmented, hermaphroditic flatworms that inhabit the intestinal lumen; and nematodes (roundworms), which are dioecious, cylindrical parasites that inhabit intestinal and peripheral tissue sites. Helminths exhibit a sublime co-evolution with the host's immune system that has enabled them to successfully colonize almost all multicellular species present in every geographical environment, including over two billion humans. In the face of this challenge, the host immune system has evolved to strike a delicate balance between attempts to neutralize the infectious assault versus limitation of damage to host tissues. Among the most important cell types during helminthic invasion are granulocytes: eosinophils, neutrophils and basophils. Depending on the specific context, these leukocytes may have pivotal roles in host protection, immunopathology, or facilitation of helminth establishment. This review provides an overview of the function of granulocytes in helminthic infections.}, } @article {pmid22357931, year = {2012}, author = {Kawabe, Y and Weening, KE and Marquay-Markiewicz, J and Schaap, P}, title = {Evolution of self-organisation in Dictyostelia by adaptation of a non-selective phosphodiesterase and a matrix component for regulated cAMP degradation.}, journal = {Development (Cambridge, England)}, volume = {139}, number = {7}, pages = {1336-1345}, pmid = {22357931}, issn = {1477-9129}, support = {BB/E016308/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 090276/WT_/Wellcome Trust/United Kingdom ; BB/D013453/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/G020426/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {3',5'-Cyclic-AMP Phosphodiesterases/genetics/*physiology ; Cloning, Molecular ; Cyclic AMP/metabolism ; Cysteine/chemistry ; Developmental Biology/methods ; Dictyostelium ; Gene Expression Regulation, Developmental ; Genetic Complementation Test ; Models, Biological ; Phenotype ; Phylogeny ; Promoter Regions, Genetic ; Protein Isoforms ; Protein Structure, Tertiary ; }, abstract = {Dictyostelium discoideum amoebas coordinate aggregation and morphogenesis by secreting cyclic adenosine monophosphate (cAMP) pulses that propagate as waves through fields of cells and multicellular structures. To retrace how this mechanism for self-organisation evolved, we studied the origin of the cAMP phosphodiesterase PdsA and its inhibitor PdiA, which are essential for cAMP wave propagation. D. discoideum and other species that use cAMP to aggregate reside in group 4 of the four major groups of Dictyostelia. We found that groups 1-3 express a non-specific, low affinity orthologue of PdsA, which gained cAMP selectivity and increased 200-fold in affinity in group 4. A low affinity group 3 PdsA only partially restored aggregation of a D. discoideum pdsA-null mutant, but was more effective at restoring fruiting body morphogenesis. Deletion of a group 2 PdsA gene resulted in disruption of fruiting body morphogenesis, but left aggregation unaffected. Together, these results show that groups 1-3 use a low affinity PdsA for morphogenesis that is neither suited nor required for aggregation. PdiA belongs to a family of matrix proteins that are present in all Dictyostelia and consist mainly of cysteine-rich repeats. However, in its current form with several extensively modified repeats, PdiA is only present in group 4. PdiA is essential for initiating spiral cAMP waves, which, by organising large territories, generate the large fruiting structures that characterise group 4. We conclude that efficient cAMP-mediated aggregation in group 4 evolved by recruitment and adaptation of a non-selective phosphodiesterase and a matrix component into a system for regulated cAMP degradation.}, } @article {pmid22353663, year = {2011}, author = {Zaina, S and Lund, G}, title = {Epigenetics: a tool to understand diet-related cardiovascular risk?.}, journal = {Journal of nutrigenetics and nutrigenomics}, volume = {4}, number = {5}, pages = {261-274}, doi = {10.1159/000334584}, pmid = {22353663}, issn = {1661-6758}, mesh = {Animals ; Atherosclerosis/genetics ; Cardiovascular Diseases/*genetics ; DNA/metabolism ; DNA Methylation ; *Diet ; *Epigenesis, Genetic ; *Epigenomics ; Genetic Variation ; Humans ; Models, Biological ; Models, Genetic ; Nutritional Sciences ; Risk Factors ; Transcription, Genetic ; }, abstract = {Cardiovascular disease (CVD) is a leading cause of mortality and is projected to hold its grim record as developing countries increase their wealth. Since specific nutritional habits are important risk factors for CVD, it is imperative to understand how ingredients of risk-associated diets convert a healthy cellular transcriptional program into a pathological one. Epigenetics has enriched our view of the genome by showing that DNA-associated regulatory proteins and RNAs, together with chemical modifications of the DNA itself, determine which parts of the DNA chain are transcribed or silent in a given phase of a cell's life. This complex biological entity--the epigenome--accounts for the enormous phenotypic diversity within a multicellular organism despite its unicellular origin. Crucially, the epigenome can be modified by diet and other exogenous factors, thus suggesting that epigenetic mechanisms might underlie pathological responses to CVD risk factors. Here, we will review the current knowledge of epigenetic mechanisms in diet-gene interactions and propose ways in which epigenetics might clarify the impact of genetic variants on CVD risk.}, } @article {pmid22328715, year = {2012}, author = {Yang, D and Zhong, F and Li, D and Liu, Z and Wei, H and Jiang, Y and He, F}, title = {General trends in the utilization of structural factors contributing to biological complexity.}, journal = {Molecular biology and evolution}, volume = {29}, number = {8}, pages = {1957-1968}, doi = {10.1093/molbev/mss064}, pmid = {22328715}, issn = {1537-1719}, mesh = {Animals ; Databases, Protein ; *Evolution, Molecular ; Genome/genetics ; Humans ; Protein Structure, Tertiary ; Proteins/*chemistry/*genetics ; Proteome/genetics/metabolism ; Species Specificity ; }, abstract = {During evolution, proteins containing newly emerged domains and the increasing proportion of multidomain proteins in the full genome-encoded proteome (GEP) have substantially contributed to increasing biological complexity. However, it is not known how these two potential structural factors are preferentially utilized at given physiological states. Here, we classified proteins according to domain number and domain age and explored the general trends across species for the utilization of proteins from GEP to various certain-state proteomes (CSPs, i.e., all the proteins expressed at certain physiological states). We found that multidomain proteins or only older domain-containing proteins are significantly overrepresented in CSPs compared with GEP, which is a trend that is stronger in multicellular organisms than in unicellular organisms. Interestingly, the strengths of overrepresentation decreased during evolution of multicellular eukaryotes. When comparing across CSPs, we found that multidomain proteins are more overrepresented in complex tissues than in simpler ones, whereas no difference among proteins with domains of different ages is evident between complex and simple tissues. Thus, biological complexity under certain conditions is more significantly realized by diverse domain organization than by the emergence of new types of domain. In addition, we found that multidomain or only older domain-containing proteins tend to evolve slowly and generally are under stronger purifying selection, which may partly result from their general overrepresentation trends in CSPs.}, } @article {pmid22326743, year = {2012}, author = {Cai, X}, title = {Evolutionary genomics reveals the premetazoan origin of opposite gating polarity in animal-type voltage-gated ion channels.}, journal = {Genomics}, volume = {99}, number = {4}, pages = {241-245}, doi = {10.1016/j.ygeno.2012.01.007}, pmid = {22326743}, issn = {1089-8646}, mesh = {Amino Acid Sequence ; Animals ; Biophysics ; Calcium Channels/*genetics ; Choanoflagellata/*genetics ; Cyclic Nucleotide-Gated Cation Channels/genetics ; *Evolution, Molecular ; Genomics/methods ; Molecular Sequence Data ; Nucleotides, Cyclic/genetics ; Phylogeny ; Potassium Channels, Voltage-Gated/*genetics ; Protein Structure, Tertiary/genetics ; Sequence Alignment ; Sodium Channels/*genetics ; }, abstract = {Electrical signaling in animals ensures the rapid and accurate transmission of information, often carried by voltage-gated Na(+), Ca(2+) and K(+) channels that are activated by membrane depolarization. In heart and neurons, a distinct type of ion channel called the hyperpolarization-activated, cyclic nucleotide-regulated (HCN) channel is activated by membrane hyperpolarization. Recent genomic studies have revealed that animal-type voltage-gated Na(+) channels (Liebeskind BJ, et al. 2011. Proc Natl Acad Sci U S A. 108:9154) had evolved in choanoflagellates, one of the unicellular relatives of animals. To date, HCN channels have been considered to be animal-specific. Here, we demonstrate the presence of an HCN channel homolog (SroHCN) in the choanoflagellate protist Salpingoeca rosetta. SroHCN contains highly conserved functional domains and sequence motifs that are correlated with the unique biophysical activities of HCN channels. These findings provide novel genomic insights into the evolution of complex electrical signaling before the emergence of multicellular animals.}, } @article {pmid22326460, year = {2012}, author = {Robinson, AJ and Kunji, ER and Gross, A}, title = {Mitochondrial carrier homolog 2 (MTCH2): the recruitment and evolution of a mitochondrial carrier protein to a critical player in apoptosis.}, journal = {Experimental cell research}, volume = {318}, number = {11}, pages = {1316-1323}, doi = {10.1016/j.yexcr.2012.01.026}, pmid = {22326460}, issn = {1090-2422}, support = {MC_U105663139/MRC_/Medical Research Council/United Kingdom ; MC_U105674181/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Apoptosis ; Choanoflagellata ; Evolution, Molecular ; Humans ; Mitochondrial Membrane Transport Proteins/genetics/metabolism/*physiology ; Mitochondrial Proteins/metabolism/physiology ; Protein Transport ; }, abstract = {Recent studies report mitochondrial carrier homolog 2 (MTCH2) as a novel and uncharacterized protein that acts as a receptor-like protein for the truncated BH3-interacting domain death agonist (tBID) protein in the outer membrane of mitochondria. These studies, using mouse embryonic stem cells and fibroblasts as well as mice with a conditional knockout of MTCH2 in the liver, showed that deletion of MTCH2 hindered recruitment of tBID to the mitochondria with subsequent reductions in the activation of pro-apoptotic proteins, mitochondrial outer membrane permeabilization and apoptosis. Sequence analysis shows that MTCH2 is present in all examined multicellular Metazoa as well as unicellular Choanoflagellata, and is a highly derived member of the mitochondrial carrier family. Mitochondrial carriers are monomeric transport proteins that are usually found in the inner mitochondrial membrane, where they exchange small substrates between the mitochondrial matrix and intermembrane space. There are extensive differences between the protein sequences of MTCH2 and other mitochondrial carriers that may explain the ability of MTCH2 to associate with tBID and thus its role in apoptosis. We review the experimental evidence for the role of MTCH2 in apoptosis and suggest that the original transport function of the ancestral MTCH2 mitochondrial carrier has been co-opted by the apoptotic machinery to provide a receptor and signaling mechanism.}, } @article {pmid22322874, year = {2011}, author = {Lozada-Chávez, I and Stadler, PF and Prohaska, SJ}, title = {"Hypothesis for the modern RNA world": a pervasive non-coding RNA-based genetic regulation is a prerequisite for the emergence of multicellular complexity.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {41}, number = {6}, pages = {587-607}, pmid = {22322874}, issn = {1573-0875}, mesh = {Bacteria/chemistry/genetics ; *Biological Evolution ; DNA/chemistry/genetics/metabolism ; Eukaryota/chemistry/*genetics/metabolism ; *Evolution, Molecular ; Gene Expression Regulation ; RNA, Untranslated/chemistry/*genetics/metabolism ; }, abstract = {The transitions to multicellularity mark the most pivotal and distinctive events in life's history on Earth. Although several transitions to "simple" multicellularity (SM) have been recorded in both bacterial and eukaryotic clades, transitions to complex multicellularity (CM) have only happened a few times in eukaryotes. A large number of cell types (associated with large body size), increased energy consumption per gene expressed, and an increment of non-protein-coding DNA positively correlate with CM. These three factors can indeed be understood as the causes and consequences of the regulation of gene expression. Here, we discuss how a vast expansion of non-protein-coding RNA (ncRNAs) regulators rather than large numbers of novel protein regulators can easily contribute to the emergence of CM. We also propose that the evolutionary advantage of RNA-based gene regulation derives from the robustness of the RNA structure that makes it easy to combine genetic drift with functional exploration. We describe a model which aims to explain how the evolutionary dynamic of ncRNAs becomes dominated by the accessibility of advantageous mutations to innovate regulation in complex multicellular organisms. The information and models discussed here outline the hypothesis that pervasive ncRNA-based regulatory systems, only capable of being expanded and explored in higher eukaryotes, are prerequisite to complex multicellularity. Thereby, regulatory RNA molecules in Eukarya have allowed intensification of morphological complexity by stabilizing critical phenotypes and controlling developmental precision. Although the origin of RNA on early Earth is still controversial, it is becoming clear that once RNA emerged into a protocellular system, its relevance within the evolution of biological systems has been greater than we previously thought.}, } @article {pmid22319146, year = {2012}, author = {Bedhomme, S and Lafforgue, G and Elena, SF}, title = {Multihost experimental evolution of a plant RNA virus reveals local adaptation and host-specific mutations.}, journal = {Molecular biology and evolution}, volume = {29}, number = {5}, pages = {1481-1492}, doi = {10.1093/molbev/msr314}, pmid = {22319146}, issn = {1537-1719}, mesh = {Analysis of Variance ; Consensus Sequence ; *Evolution, Molecular ; Genome, Viral ; Host-Pathogen Interactions/*genetics ; Models, Genetic ; Mutation ; Potyvirus/*genetics/pathogenicity ; Selection, Genetic ; Solanaceae/physiology/virology ; }, abstract = {For multihost pathogens, adaptation to multiple hosts has important implications for both applied and basic research. At the applied level, it is one of the main factors determining the probability and the severity of emerging disease outbreaks. At the basic level, it is thought to be a key mechanism for the maintenance of genetic diversity both in host and pathogen species. Using Tobacco etch potyvirus (TEV) and four natural hosts, we have designed an evolution experiment whose strength and novelty are the use of complex multicellular host organism as hosts and a high level of replication of different evolutionary histories and lineages. A pattern of local adaptation, characterized by a higher infectivity and virulence on host(s) encountered during the experimental evolution was found. Local adaptation only had a cost in terms of performance on other hosts in some cases. We could not verify the existence of a cost for generalists, as expected to arise from antagonistic pleiotropy and other genetic mechanisms generating a fitness trade-off between hosts. This observation confirms that this classical theoretical prediction lacks empirical support. We discuss the reasons for this discrepancy between theory and experiment in the light of our results. The analysis of full genome consensus sequences of the evolved lineages established that all mutations shared between lineages were host specific. A low degree of parallel evolution was observed, possibly reflecting the various adaptive pathways available for TEV in each host. Altogether, these results reveal a strong adaptive potential of TEV to new hosts without severe evolutionary constraints.}, } @article {pmid22307617, year = {2012}, author = {Ratcliff, WC and Denison, RF and Borrello, M and Travisano, M}, title = {Experimental evolution of multicellularity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {5}, pages = {1595-1600}, pmid = {22307617}, issn = {1091-6490}, mesh = {Apoptosis ; *Biological Evolution ; Genes, Fungal ; Genotype ; Saccharomyces cerevisiae/*cytology/genetics ; }, abstract = {Multicellularity was one of the most significant innovations in the history of life, but its initial evolution remains poorly understood. Using experimental evolution, we show that key steps in this transition could have occurred quickly. We subjected the unicellular yeast Saccharomyces cerevisiae to an environment in which we expected multicellularity to be adaptive. We observed the rapid evolution of clustering genotypes that display a novel multicellular life history characterized by reproduction via multicellular propagules, a juvenile phase, and determinate growth. The multicellular clusters are uniclonal, minimizing within-cluster genetic conflicts of interest. Simple among-cell division of labor rapidly evolved. Early multicellular strains were composed of physiologically similar cells, but these subsequently evolved higher rates of programmed cell death (apoptosis), an adaptation that increases propagule production. These results show that key aspects of multicellular complexity, a subject of central importance to biology, can readily evolve from unicellular eukaryotes.}, } @article {pmid22305980, year = {2012}, author = {Yamada, M and Okura, Y and Suzuki, Y and Fukumura, S and Miyazaki, T and Ikeda, H and Takezaki, S and Kawamura, N and Kobayashi, I and Ariga, T}, title = {Somatic mosaicism in two unrelated patients with X-linked chronic granulomatous disease characterized by the presence of a small population of normal cells.}, journal = {Gene}, volume = {497}, number = {1}, pages = {110-115}, doi = {10.1016/j.gene.2012.01.019}, pmid = {22305980}, issn = {1879-0038}, mesh = {Adolescent ; Child, Preschool ; Genes, X-Linked ; Granulomatous Disease, Chronic/*genetics ; Humans ; Male ; Membrane Glycoproteins/genetics ; *Mosaicism ; Mutation ; NADPH Oxidase 2 ; NADPH Oxidases/genetics ; }, abstract = {X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency disease of phagocytes caused by mutations in the cytochrome b(558)β (CYBB) gene. We, for the first time, detected somatic mosaicism in two unrelated male patients with X-CGD caused by de novo nonsense mutations (p.Gly223X and p.Glu462X) in the CYBB gene. In each patient, a small subset of granulocytes was normal in terms of respiratory burst (ROB) activity, gp91(phox) expression, and CYBB sequences. Cells with wild-type CYBB sequence were also detected in buccal swab specimens and in peripheral blood mononuclear cells. The normal cells were shown to be of the patient origin by fluorescent in situ hybridization analysis of X/Y chromosomes, and by HLA DNA typing. Two possible mechanisms for this somatic mosaicism were considered. The first is that the de novo disease-causing mutations in CYBB occurred at an early multicellular stage of embryogenesis with subsequent expansion of the mutated cells, leaving some unmutated cells surviving. The second possibility is that the de novo mutations occurred in oocytes which was followed by reversion of the mutations in a small subset of cells in early embryogenesis.}, } @article {pmid22301955, year = {2012}, author = {Sørensen, I and Rose, JK and Doyle, JJ and Domozych, DS and Willats, WG}, title = {The Charophycean green algae as model systems to study plant cell walls and other evolutionary adaptations that gave rise to land plants.}, journal = {Plant signaling & behavior}, volume = {7}, number = {1}, pages = {1-3}, pmid = {22301955}, issn = {1559-2324}, mesh = {*Adaptation, Physiological ; *Biological Evolution ; Cell Wall/*physiology ; Chlorophyta/*genetics/physiology ; *Models, Biological ; }, abstract = {The Charophycean green algae (CGA) occupy a key phylogenetic position as the evolutionary grade that includes the sister group of the land plants (embryophytes), and so provide potentially valuable experimental systems to study the development and evolution of traits that were necessary for terrestrial colonization. The nature and molecular bases of such traits are still being determined, but one critical adaptation is thought to have been the evolution of a complex cell wall. Very little is known about the identity, origins and diversity of the biosynthetic machinery producing the major suites of structural polymers (i. e., cell wall polysaccharides and associated molecules) that must have been in place for land colonization. However, it has been suggested that the success of the earliest land plants was partly based on the frequency of gene duplication, and possibly whole genome duplications, during times of radical habitat changes. Orders of the CGA span early diverging taxa retaining more ancestral characters, through complex multicellular organisms with morphological characteristics resembling those of land plants. Examination of gene diversity and evolution within the CGA could help reveal when and how the molecular pathways required for synthesis of key structural polymers in land plants arose.}, } @article {pmid22301644, year = {2012}, author = {Coelho, SM and Scornet, D and Rousvoal, S and Peters, NT and Dartevelle, L and Peters, AF and Cock, JM}, title = {Ectocarpus: a model organism for the brown algae.}, journal = {Cold Spring Harbor protocols}, volume = {2012}, number = {2}, pages = {193-198}, doi = {10.1101/pdb.emo065821}, pmid = {22301644}, issn = {1559-6095}, mesh = {Biological Evolution ; Molecular Biology/*methods ; Phaeophyta/genetics/metabolism/*physiology ; }, abstract = {The brown algae are an interesting group of organisms from several points of view. They are the dominant organisms in many coastal ecosystems, where they often form large, underwater forests. They also have an unusual evolutionary history, being members of the stramenopiles, which are very distantly related to well-studied animal and green plant models. As a consequence of this history, brown algae have evolved many novel features, for example in terms of their cell biology and metabolic pathways. They are also one of only a small number of eukaryotic groups to have independently evolved complex multicellularity. Despite these interesting features, the brown algae have remained a relatively poorly studied group. This situation has started to change over the last few years, however, with the emergence of the filamentous brown alga Ectocarpus as a model system that is amenable to the genomic and genetic approaches that have proved to be so powerful in more classical model organisms such as Drosophila and Arabidopsis.}, } @article {pmid22292107, year = {2011}, author = {Stamati, K and Mudera, V and Cheema, U}, title = {Evolution of oxygen utilization in multicellular organisms and implications for cell signalling in tissue engineering.}, journal = {Journal of tissue engineering}, volume = {2}, number = {1}, pages = {2041731411432365}, pmid = {22292107}, issn = {2041-7314}, abstract = {Oxygen is one of the critically defining elements resulting in the existence of eukaryotic life on this planet. The rise and fall of this element can be tracked through time and corresponds with the evolution of diverse life forms, development of efficient energy production (oxidative phosphorylation) in single cell organisms, the evolution of multicellular organisms and the regulation of complex cell phenotypes. By understanding these events, we can plot the effect of oxygen on evolution and its direct influence on different forms of life today, from the whole organism to specific cells within multicellular organisms. In the emerging field of tissue engineering, understanding the role of different levels of oxygen for normal cell function as well as control of complex signalling cascades is paramount to effectively build 3D tissues in vitro and their subsequent survival when implanted.}, } @article {pmid22289038, year = {2013}, author = {Liotier, PJ and Rossi, JM and Wendling-Mansuy, S and Chabrand, P}, title = {Trabecular bone remodelling under pathological conditions based on biochemical and mechanical processes involved in BMU activity.}, journal = {Computer methods in biomechanics and biomedical engineering}, volume = {16}, number = {11}, pages = {1150-1162}, doi = {10.1080/10255842.2012.654781}, pmid = {22289038}, issn = {1476-8259}, mesh = {Algorithms ; Bone Remodeling/*physiology ; Bone Resorption/physiopathology ; Bone and Bones/metabolism ; Humans ; Kinetics ; Mechanical Phenomena ; *Models, Biological ; Osteoclasts/metabolism ; Osteocytes/metabolism ; Osteoporosis ; }, abstract = {In adulthood, bone tissue is continuously renewed by processes governed by basic multicellular units composed of osteocytes, osteoclasts and osteoblasts, which are subjected to local mechanical loads. Osteocytes are known to be integrated mechanosensors that regulate the activation of the osteoclasts and osteoblasts involved in bone resorption and apposition processes, respectively. After collagen tissue apposition, a process of collagen mineralisation takes place, gradually increasing the effective stiffness of bone. This study presents a new model based on physicochemical parameters involved in spongy bone remodelling under pathological conditions. Our model simulates the transient evolution of both geometry and effective Young's modulus of the trabeculae, also taking turnover into account. Various loads were applied on a trabecula in order to determine the evolution of bone volume fraction under pathological conditions. A parametric study performed on the model showed that one key parameter here is the kinetic constant of hydroxyapatite crystallisation. We subsequently tested our model on a pathological case approaching osteoporosis, involving a decrease in the number of viable osteocytes present in bone. The model converges to a lower value (- 5%) for bone volume fraction than with a normal quantity of osteocytes. This useful tool offers new perspectives for predicting bone remodelling deficits on a local scale in patients with pathological conditions such as osteoporosis and in bedridden patients, as well as for astronauts subjected to weightlessness in space.}, } @article {pmid22282802, year = {2012}, author = {Bornens, M}, title = {The centrosome in cells and organisms.}, journal = {Science (New York, N.Y.)}, volume = {335}, number = {6067}, pages = {422-426}, doi = {10.1126/science.1209037}, pmid = {22282802}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Cell Movement ; Cell Nucleus/*physiology/ultrastructure ; *Cell Polarity ; Centrioles/*physiology ; Centrosome/chemistry/*physiology/ultrastructure ; Cilia/physiology ; Embryo, Nonmammalian/physiology ; Embryonic Development ; Fertilization ; Humans ; Spindle Apparatus/physiology/ultrastructure ; }, abstract = {The centrosome acts as the main microtubule-nucleating organelle in animal cells and plays a critical role in mitotic spindle orientation and in genome stability. Yet, despite its central role in cell biology, the centrosome is not present in all multicellular organisms or in all cells of a given organism. The main outcome of centrosome reproduction is the transmission of polarity to daughter cells and, in most animal species, the sperm-donated centrosome defines embryo polarity. Here I will discuss the role of the centrosome in cell polarity, resulting from its ability to position the nucleus at the cell center, and discuss how centrosome innovation might have been critical during metazoan evolution.}, } @article {pmid22258316, year = {2012}, author = {Cai, X}, title = {Ancient origin of four-domain voltage-gated Na+ channels predates the divergence of animals and fungi.}, journal = {The Journal of membrane biology}, volume = {245}, number = {2}, pages = {117-123}, pmid = {22258316}, issn = {1432-1424}, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Fungi/*genetics/metabolism ; Ion Channel Gating/*genetics ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Sequence Alignment/methods ; Sodium Channels/*genetics/metabolism ; }, abstract = {The four-domain voltage-gated Na(+) channels are believed to have arisen in multicellular animals, possibly during the evolution of the nervous system. Recent genomic studies reveal that many ion channels, including Na(+) channels and Ca(2+) channels previously thought to be restricted to animals, can be traced back to one of the unicellular ancestors of animals, Monosiga brevicollis. The eukaryotic supergroup Opisthokonta contains animals, fungi, and a diverse group of their unicellular relatives including M. brevicollis. Here, we demonstrate the presence of a putative voltage-gated Na(+) channel homolog (TtrNa(V)) in the apusozoan protist Thecamonas trahens, which belongs to the unicellular sister group to Opisthokonta. TtrNa(V) displays a unique selectivity motif distinct from most animal voltage-gated Na(+) channels. The identification of TtrNa(V) suggests that voltage-gated Na(+) channels might have evolved before the divergence of animals and fungi. Furthermore, our analyses reveal that Na(V) channels have been lost independently in the amoeboid holozoan Capsaspora owczarzaki of the animal lineage and in several basal fungi. These findings provide novel insights into the evolution of four-domain voltage-gated ion channels, ion selectivity, and membrane excitability in the Opisthokonta lineage.}, } @article {pmid22247052, year = {2012}, author = {Manuel, M and Forêt, S}, title = {Searching for Eve: basal metazoans and the evolution of multicellular complexity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {34}, number = {3}, pages = {247-251}, doi = {10.1002/bies.201100183}, pmid = {22247052}, issn = {1521-1878}, mesh = {Animals ; *Biological Evolution ; Body Patterning ; Cell Proliferation ; Gene Expression Profiling/methods ; *Gene Expression Regulation ; Models, Biological ; Phylogeny ; Porifera/classification/genetics/growth & development/*physiology ; Stem Cells/cytology/physiology ; }, } @article {pmid22232763, year = {2012}, author = {Pires, ND and Dolan, L}, title = {Morphological evolution in land plants: new designs with old genes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {367}, number = {1588}, pages = {508-518}, pmid = {22232763}, issn = {1471-2970}, support = {BBS/E/J/00000168/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Carbon Cycle ; Embryophyta/classification/*genetics/growth & development/radiation effects ; *Gene Expression Regulation, Plant ; *Genes, Plant ; Germ Cells, Plant/cytology/growth & development ; Morphogenesis ; Phylogeny ; Plant Leaves/genetics/growth & development ; Plant Proteins/genetics ; Plant Roots/genetics/growth & development ; Signal Transduction ; Transcription Factors/genetics ; }, abstract = {The colonization and radiation of multicellular plants on land that started over 470 Ma was one of the defining events in the history of this planet. For the first time, large amounts of primary productivity occurred on the continental surface, paving the way for the evolution of complex terrestrial ecosystems and altering global biogeochemical cycles; increased weathering of continental silicates and organic carbon burial resulted in a 90 per cent reduction in atmospheric carbon dioxide levels. The evolution of plants on land was itself characterized by a series of radical transformations of their body plans that included the formation of three-dimensional tissues, de novo evolution of a multicellular diploid sporophyte generation, evolution of multicellular meristems, and the development of specialized tissues and organ systems such as vasculature, roots, leaves, seeds and flowers. In this review, we discuss the evolution of the genes and developmental mechanisms that drove the explosion of plant morphologies on land. Recent studies indicate that many of the gene families which control development in extant plants were already present in the earliest land plants. This suggests that the evolution of novel morphologies was to a large degree driven by the reassembly and reuse of pre-existing genetic mechanisms.}, } @article {pmid22229263, year = {2012}, author = {Dridi, B and Raoult, D and Drancourt, M}, title = {Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry identification of Archaea: towards the universal identification of living organisms.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {120}, number = {2}, pages = {85-91}, doi = {10.1111/j.1600-0463.2011.02833.x}, pmid = {22229263}, issn = {1600-0463}, mesh = {Archaea/*chemistry/*classification/genetics/isolation & purification ; Archaeal Proteins/*analysis ; Phylogeny ; Reproducibility of Results ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods ; }, abstract = {Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) identification of Archaea has been limited to some environmental extremophiles belonging to distant taxa. We developed a specific protocol for MALDI-TOF-MS identification of Archaea and applied it to seven environmental human-associated Methanobrevibacter smithii, Methanobrevibacter oralis, Methanosphaera stadtmanae, and the recently described Methanomassiliicoccus luminyensi Archaea. After mechanical lyse, we observed a unique protein profile for each organisms comprising 7-24 peaks ranging from 3,015 to 10,632 Da with a high quality score of 7.38 ± 1.26. Profiles were reproducible over successive experiments performed at 1, 2, and 3-week growth durations and unambiguously distinguished the Archaea from all of the 3,995 bacterial spectra in the Brüker database. After the incorporation of the determined profiles into a local database, archaeal isolates were blindly identified within 10 min with an identification score of 1.9-2.3. The MALDI-TOF-MS-based clustering of these archaeal organisms was consistent with their 16S rDNA sequence-based phylogeny. These data prove that MALDI-TOF-MS profiling could be used as a first-line technique for the identification of human Archaea. In complement to previous reports for animal cells, Bacteria and giant viruses, MALDI-TOF-MS therefore appears as a universal method for the identification of living unicellular and multicellular organisms.}, } @article {pmid22226831, year = {2012}, author = {Back, P and De Vos, WH and Depuydt, GG and Matthijssens, F and Vanfleteren, JR and Braeckman, BP}, title = {Exploring real-time in vivo redox biology of developing and aging Caenorhabditis elegans.}, journal = {Free radical biology & medicine}, volume = {52}, number = {5}, pages = {850-859}, doi = {10.1016/j.freeradbiomed.2011.11.037}, pmid = {22226831}, issn = {1873-4596}, mesh = {Age Factors ; Animals ; Animals, Genetically Modified ; Bacterial Proteins/biosynthesis/metabolism ; Biosensing Techniques ; Caenorhabditis elegans/growth & development/*metabolism ; Gene Expression Regulation ; Genitalia/metabolism ; Glutathione/metabolism ; Glutathione Disulfide/metabolism ; Green Fluorescent Proteins/biosynthesis/metabolism ; Head ; Hydrogen Peroxide/metabolism/*pharmacology ; Life Expectancy ; Luminescent Proteins/biosynthesis/metabolism ; Muscles/metabolism ; Organ Specificity ; Oxidants/metabolism/*pharmacology ; Oxidation-Reduction ; Recombinant Fusion Proteins/biosynthesis/metabolism ; Tail/metabolism ; }, abstract = {Reactive oxygen species (ROS) are no longer considered merely toxic by-products of the oxidative metabolism. Tightly controlled concentrations of ROS and fluctuations in redox potential may be important mediators of signaling processes. Understanding the role of ROS and redox status in physiology, stress response, development, and aging requires their nondisruptive, spatiotemporal, real-time quantification in a living organism. We established Caenorhabditis elegans strains bearing the genetically encoded fluorescent biosensors HyPer and Grx1-roGFP2 for the detection of hydrogen peroxide (H(2)O(2)) and the glutathione redox potential, respectively. Although, given its transparency and genetic tractability, C. elegans is perfectly suitable as a model organism for such approaches, they have never been tried before in this nematode. We found that H(2)O(2) treatment clearly induces a dose-dependent, reversible response of both biosensors in the living worms. The ratio of oxidized to reduced glutathione decreases during postembryonic development. H(2)O(2) levels increase with age and this effect is delayed when life span is extended by dietary restriction. In young adults, we detected several regions with distinct redox properties that may be linked to their biological function. Our findings demonstrate that genetically encoded biosensors can reveal previously unknown details of in vivo redox biology in multicellular organisms.}, } @article {pmid22220352, year = {2011}, author = {Beloussov, LV}, title = {Nomothetics and idiography in developmental biology.}, journal = {Theoretical biology forum}, volume = {104}, number = {1}, pages = {15-33}, pmid = {22220352}, issn = {2282-2593}, mesh = {Algorithms ; Animals ; *Developmental Biology ; Embryonic Development ; Evolution, Molecular ; *Feedback, Physiological ; Humans ; Natural History ; *Stress, Mechanical ; }, abstract = {Successions of space-temporal structures arisen during development of multicellular organisms are the most regular, complex and reproducible ones among all taking place in the entire nature without a human's intervention. Therefore, the question whether it would be possible to embrace them by a common physicalistic law (nomothetic approach) or they can be only enumerated and described one after another (idiography) is of an overall importance for the natural sciences in general. We review several nomothetic attempts performed in XX century biology and suggest that such laws may have a structure of feedback contours between the active and passive mechanical stresses generated in developing embryos. We trace several steps towards creating such contours and show that they couple mechanics with geometry providing thus a progressive complication of embryonic structure. Then we discuss, in what way genome can influence these morphomechanical laws. We speculate that the main developmental function of genome is to set up the values of the parameters, introduced in these laws. We emphasize that these parameters values acquire a definite meaning only within the context of the laws into which they are introduced.}, } @article {pmid22212997, year = {2011}, author = {Ananko, GG}, title = {A model of genetic search for beneficial mutations: estimating the constructive capacities of mutagenesis.}, journal = {Journal of molecular evolution}, volume = {73}, number = {5-6}, pages = {337-354}, pmid = {22212997}, issn = {1432-1432}, mesh = {DNA, Intergenic/genetics ; Escherichia coli/genetics ; *Evolution, Molecular ; Genome Size ; Humans ; Introns ; *Models, Genetic ; *Mutation ; Mutation Rate ; Selection, Genetic/*genetics ; }, abstract = {We attempted to answer the following question: What evolutionary conditions are required to generate novel genetic modules? Our broad formulation of the problem allows us to simultaneously consider such issues as the relationship between the stage of "genetic search" and the rate of adaptive evolution; the theoretical limits to the generative capacities of spontaneous mutagenesis; and the correlation between genome organization and evolvability. We show that adaptive evolution is feasible only when the mutation rate is fine-tuned to a specific range of values and the structures of the genome and genes are optimized in a certain way. Our quantitative analysis has demonstrated that the rate of evolution of novelty depends on several parameters, such as genome size, the length of a module, the size of the adjacent nonfunctional DNA spacers, and the mutation rate at various genomic scales. We evaluated the efficiency of some mechanisms that increase evolvability: bias in the spectrum of mutation rates towards small mutations, and the availability and size of nonfunctional DNA spacers. We show that the probability of successful duplication and insertion of a copy of a functional module increases by several orders of magnitude depending on the length of the spacers flanking the module. We infer that the adaptive evolution of multicellular organisms has become feasible because of the abundance of nonfunctional DNA spacers, particularly introns, in the genome. We also discuss possible reasons underlying evolutionary retention of the mechanisms that increase evolvability.}, } @article {pmid22209334, year = {2012}, author = {Romeralo, M and Escalante, R and Baldauf, SL}, title = {Evolution and diversity of dictyostelid social amoebae.}, journal = {Protist}, volume = {163}, number = {3}, pages = {327-343}, doi = {10.1016/j.protis.2011.09.004}, pmid = {22209334}, issn = {1618-0941}, mesh = {Amoebida/classification/genetics/growth & development/*physiology ; *Biological Evolution ; Cell Communication ; *Genetic Variation ; Phylogeny ; }, abstract = {Dictyostelid social amoebae are a large and ancient group of soil microbes with an unusual multicellular stage in their life cycle. Taxonomically, they belong to the eukaryotic supergroup Amoebozoa, the sister group to Opisthokonta (animals + fungi). Roughly half of the ~150 known dictyostelid species were discovered during the last five years and probably many more remain to be found. The traditional classification system of Dictyostelia was completely overturned by cladistic analyses and molecular phylogenies of the past six years. As a result, it now appears that, instead of three major divisions there are eight, none of which correspond to traditional higher-level taxa. In addition to the widely studied Dictyostelium discoideum, there are now efforts to develop model organisms and complete genome sequences for each major group. Thus Dictyostelia is becoming an excellent model for both practical, medically related research and for studying basic principles in cell-cell communication and developmental evolution. In this review we summarize the latest information about their life cycle, taxonomy, evolutionary history, genome projects and practical importance.}, } @article {pmid25883411, year = {2012}, author = {Umen, JG and Olson, BJ}, title = {Genomics of Volvocine Algae.}, journal = {Advances in botanical research}, volume = {64}, number = {}, pages = {185-243}, pmid = {25883411}, issn = {0065-2296}, support = {R01 GM078376/GM/NIGMS NIH HHS/United States ; R01 GM092744/GM/NIGMS NIH HHS/United States ; }, abstract = {Volvocine algae are a group of chlorophytes that together comprise a unique model for evolutionary and developmental biology. The species Chlamydomonas reinhardtii and Volvox carteri represent extremes in morphological diversity within the Volvocine clade. Chlamydomonas is unicellular and reflects the ancestral state of the group, while Volvox is multicellular and has evolved numerous innovations including germ-soma differentiation, sexual dimorphism, and complex morphogenetic patterning. The Chlamydomonas genome sequence has shed light on several areas of eukaryotic cell biology, metabolism and evolution, while the Volvox genome sequence has enabled a comparison with Chlamydomonas that reveals some of the underlying changes that enabled its transition to multicellularity, but also underscores the subtlety of this transition. Many of the tools and resources are in place to further develop Volvocine algae as a model for evolutionary genomics.}, } @article {pmid25435818, year = {2012}, author = {Shelton, DE and Desnitskiy, AG and Michod, RE}, title = {Distributions of reproductive and somatic cell numbers in diverse Volvox (Chlorophyta) species.}, journal = {Evolutionary ecology research}, volume = {14}, number = {}, pages = {707-727}, pmid = {25435818}, issn = {1522-0613}, support = {T32 GM084905/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Volvox (Chlorophyta) asexual colonies consist of two kinds of cells: a large number of small somatic cells and a few large reproductive cells. The numbers of reproductive and somatic cells correspond directly to the major components of fitness - fecundity and viability, respectively. Volvox species display diverse patterns of development that give rise to the two cell types.

QUESTIONS: For Volvox species under fixed conditions, do species differ with respect to the distribution of somatic and reproductive cell numbers in a population of asexual clones? Specifically, do they differ with respect to the dispersion of the distribution, i.e. with respect to their intrinsic variability? If so, are these differences related to major among-species developmental differences?

DATA DESCRIPTION: For each of five Volvox species, we estimate the number of somatic and reproductive cells for 40 colonies and the number of reproductive cells for an additional 200 colonies. We sampled all colonies from growing, low-density, asexual populations under standard conditions.

SEARCH METHOD: We compare the distribution of reproductive cell numbers to a Poisson distribution. We also compare the overall dispersion of reproductive cell number among species by calculating the coefficient of variation (CV). We compare the bivariate (reproductive and somatic cell) dataset to simulated datasets produced from a simple model of cell-type specification with intrinsic variability and colony size variation. This allows us to roughly estimate the level of intrinsic variability that is most consistent with our observed bivariate data (given an unknown level of size variation).

CONCLUSIONS: The overall variability (CV) in reproductive cell number is high in Volvox compared with more complex organisms. Volvox species show differences in reproductive cell number CV that were not clearly related to development, as currently understood. If we used the bivariate data and tried to account for the effects of colony size variation, we found that the species that have fast embryonic divisions and asymmetric divisions have substantially higher intrinsic variability than the species that have slow divisions and no asymmetric divisions. Under our culture conditions, the Poisson distribution is a good description of intrinsic variability in reproductive cell number for some but not all Volvox species.}, } @article {pmid24704981, year = {2012}, author = {Fontana, A and Wróbel, B}, title = {A model of evolution of development based on germline penetration of new "no-junk" DNA.}, journal = {Genes}, volume = {3}, number = {3}, pages = {492-504}, pmid = {24704981}, issn = {2073-4425}, abstract = {There is a mounting body of evidence that somatic transposition may be involved in normal development of multicellular organisms and in pathology, especially cancer. Epigenetic Tracking (ET) is an abstract model of multicellular development, able to generate complex 3-dimensional structures. Its aim is not to model the development of a particular organism nor to merely summarise mainstream knowledge on genetic regulation of development. Rather, the goal of ET is to provide a theoretical framework to test new postulated genetic mechanisms, not fully established yet in mainstream biology. The first proposal is that development is orchestrated through a subset of cells which we call driver cells. In these cells, the cellular state determines a specific pattern of gene activation which leads to the occurrence of developmental events. The second proposal is that evolution of development is affected by somatic transposition events. We postulate that when the genome of a driver cell does not specify what developmental event should be undertaken when the cell is in a particular cellular state, somatic transposition events can reshape the genome, build new regulatory regions, and lead to a new pattern of gene activation in the cell. Our third hypothesis, not supported yet by direct evidence, but consistent with some experimental observations, is that these new "no-junk" sequences-regulatory regions created by transposable elements at new positions in the genome-can exit the cell and enter the germline, to be incorporated in the genome of the progeny. We call this mechanism germline penetration. This process allows heritable incorporation of novel developmental events in the developmental trajectory. In this paper we will present the model and link these three postulated mechanisms to biological observations.}, } @article {pmid23804266, year = {2012}, author = {Zaccone, P and Hall, SW}, title = {Helminth infection and type 1 diabetes.}, journal = {The review of diabetic studies : RDS}, volume = {9}, number = {4}, pages = {272-286}, pmid = {23804266}, issn = {1614-0575}, support = {//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Diabetes Mellitus, Type 1/immunology/*parasitology/*therapy ; Helminthiasis/*immunology/parasitology ; Helminths/*immunology/physiology ; Humans ; *Therapy with Helminths ; }, abstract = {The increasing incidence of type 1 diabetes (T1D) and autoimmune diseases in industrialized countries cannot be exclusively explained by genetic factors. Human epidemiological studies and animal experimental data provide accumulating evidence for the role of environmental factors, such as infections, in the regulation of allergy and autoimmune diseases. The hygiene hypothesis has formally provided a rationale for these observations, suggesting that our co-evolution with pathogens has contributed to the shaping of the present-day human immune system. Therefore, improved sanitation, together with infection control, has removed immunoregulatory mechanisms on which our immune system may depend. Helminths are multicellular organisms that have developed a wide range of strategies to manipulate the host immune system to survive and complete their reproductive cycles successfully. Immunity to helminths involves profound changes in both the innate and adaptive immune compartments, which can have a protective effect in inflammation and autoimmunity. Recently, helminth-derived antigens and molecules have been tested in vitro and in vivo to explore possible applications in the treatment of inflammatory and autoimmune diseases, including T1D. This exciting approach presents numerous challenges that will need to be addressed before it can reach safe clinical application. This review outlines basic insight into the ability of helminths to modulate the onset and progression of T1D, and frames some of the challenges that helminth-derived therapies may face in the context of clinical translation.}, } @article {pmid23550342, year = {2012}, author = {Furman, DP and Bukharina, TA}, title = {Morphogenesis of Drosophila melanogaster macrochaetes: cell fate determination for bristle organ.}, journal = {Journal of stem cells}, volume = {7}, number = {1}, pages = {19-41}, pmid = {23550342}, issn = {1556-8539}, mesh = {Animal Structures/anatomy & histology/*cytology/*growth & development ; Animals ; Asymmetric Cell Division/genetics ; *Cell Lineage/genetics ; Drosophila melanogaster/*anatomy & histology/cytology/genetics/*growth & development ; *Morphogenesis/genetics ; Signal Transduction/genetics ; }, abstract = {Formation of specialized spatial structures comprising various cell types is most important in the ontogenesis of multicellular organisms. An example is the D. melanogaster bristle organs. Bristles (micro- and macrochaetes) are external sensory organs, elements of the peripheral nervous system, playing the role of mechanoreceptors. Their comparatively simple organization comprising only four specialized cells and a common origin of these cells make macrochaetes a convenient model for studying cell differentiation. The four cells forming bristle organ result from two successive divisions of a single cell, sensory organ precursor (SOP) cell. The number of macrochaetes on drosophila body corresponds to the number of SOP cells. The morphogenesis of macrochaetes comprises three stages, the first two determining a neural fate of the cells. The third stage is cell specialization into components of the bristle organ-neuron, thecogen, tormogen, and trichogen. Development of each bristle commences from segregation of proneural clusters, of 20-30 cells, from the massif of undifferentiated cells of the wing imaginal disc. At this stage, each cluster cell can potentially become a SOP cell. At the second stage, the only SOP cell and its position are determined within each cluster. Finally, two asymmetric divisions of the SOP cell with subsequent differentiation of the daughter cells gives the bristle organ. Several dozens genes are involved in the control of macrochaete morphogenesis. The main component of this system is the proneural genes of achaete-scute complex (AS-C). An increased content of proneural proteins fundamentally distinguished the cells that will follow the neural developmental pathway from the disc epidermal cells. A local AS-C expression, initiated at specified disc sites by specific transcription factors, determines the number and topology of proneural clusters. The expression of AS-C genes, continuing in the cells of the cluster, increases the difference in proneural protein content, first, between the cluster cells and then, between the cluster cells and the single SOP cell, where it reaches the maximum level. This process is provided by both the intracellular regulation of AS-C gene activity and intercellular events mediated via the EGFR and Notch signaling pathways. The third stage in macrochaete morphogenesis comprises two successive asymmetric SOP cell divisions, determining the final specialization. The selector genes, in particular, numb, neuralized, tramtrack, and musashi, play the key role in cell type specification. This review systematizes the data on molecular genetic system controlling drosophila bristle morphogenesis and proposes an integral scheme of its functioning.}, } @article {pmid22206406, year = {2011}, author = {Höhn, S and Hallmann, A}, title = {There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator.}, journal = {BMC biology}, volume = {9}, number = {}, pages = {89}, pmid = {22206406}, issn = {1741-7007}, mesh = {Actins/metabolism ; Cell Division ; Cell Movement ; Cell Nucleus ; Epithelial Cells/*cytology/ultrastructure ; Microscopy, Electron, Scanning ; *Morphogenesis ; Volvox/*cytology/growth & development/ultrastructure ; }, abstract = {BACKGROUND: Epithelial folding is a common morphogenetic process during the development of multicellular organisms. In metazoans, the biological and biomechanical processes that underlie such three-dimensional (3D) developmental events are usually complex and difficult to investigate. Spheroidal green algae of the genus Volvox are uniquely suited as model systems for studying the basic principles of epithelial folding. Volvox embryos begin life inside out and then must turn their spherical cell monolayer outside in to achieve their adult configuration; this process is called 'inversion.' There are two fundamentally different sequences of inversion processes in Volvocaceae: type A and type B. Type A inversion is well studied, but not much is known about type B inversion. How does the embryo of a typical type B inverter, V. globator, turn itself inside out?

RESULTS: In this study, we investigated the type B inversion of V. globator embryos and focused on the major movement patterns of the cellular monolayer, cell shape changes and changes in the localization of cytoplasmic bridges (CBs) connecting the cells. Isolated intact, sectioned and fragmented embryos were analyzed throughout the inversion process using light microscopy, confocal laser scanning microscopy, scanning electron microscopy and transmission electron microscopy techniques. We generated 3D models of the identified cell shapes, including the localizations of CBs. We show how concerted cell-shape changes and concerted changes in the position of cells relative to the CB system cause cell layer movements and turn the spherical cell monolayer inside out. The type B inversion of V. globator is compared to the type A inversion in V. carteri.

CONCLUSIONS: Concerted, spatially and temporally coordinated changes in cellular shapes in conjunction with concerted migration of cells relative to the CB system are the causes of type B inversion in V. globator. Despite significant similarities between type A and type B inverters, differences exist in almost all details of the inversion process, suggesting analogous inversion processes that arose through parallel evolution. Based on our results and due to the cellular biomechanical implications of the involved tensile and compressive forces, we developed a global mechanistic scenario that predicts epithelial folding during embryonic inversion in V. globator.}, } @article {pmid22203990, year = {2012}, author = {Kempes, CP and Dutkiewicz, S and Follows, MJ}, title = {Growth, metabolic partitioning, and the size of microorganisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {2}, pages = {495-500}, pmid = {22203990}, issn = {1091-6490}, mesh = {*Biological Evolution ; Biosynthetic Pathways/*physiology ; Energy Metabolism/*physiology ; Eukaryota/cytology/*growth & development ; *Models, Biological ; Population Density ; Prokaryotic Cells/cytology/*physiology ; Species Specificity ; }, abstract = {Population growth rate is a fundamental ecological and evolutionary characteristic of living organisms, but individuals must balance the metabolism devoted to biosynthesis and reproduction against the maintenance of existing structure and other functionality. Here we present a mathematical model that relates metabolic partitioning to the form of growth. The model captures the observed growth trajectory of single cells and individuals for a variety of species and taxa spanning prokaryotes, unicellular eukaryotes, and small multicellular eukaryotes. Our analysis suggests that the per-unit costs of biosynthesis and maintenance are conserved across prokaryotes and eukaryotes. However, the relative metabolic expenditure on growth and maintenance of whole organisms clearly differentiates taxa: prokaryotes spend an increasing fraction of their entire metabolism on growth with increasing cell size, whereas eukaryotes devote a diminishing fraction. These differences allow us to predict the minimum and maximum size for each taxonomic group, anticipating observed evolutionary life-history transitions. The framework provides energetic insights into taxonomic tradeoffs related to growth and metabolism and constrains traits that are important for size-structured modeling of microbial communities and their ecological and biogeochemical effects.}, } @article {pmid22200599, year = {2012}, author = {Rajendran, KV and Zhang, J and Liu, S and Kucuktas, H and Wang, X and Liu, H and Sha, Z and Terhune, J and Peatman, E and Liu, Z}, title = {Pathogen recognition receptors in channel catfish: I. Identification, phylogeny and expression of NOD-like receptors.}, journal = {Developmental and comparative immunology}, volume = {37}, number = {1}, pages = {77-86}, doi = {10.1016/j.dci.2011.12.005}, pmid = {22200599}, issn = {1879-0089}, mesh = {Animals ; Edwardsiella ictaluri ; Enterobacteriaceae Infections/immunology/metabolism/veterinary ; Fish Diseases/immunology/metabolism ; Fish Proteins/*genetics/metabolism ; *Gene Expression ; Gene Expression Regulation ; Ictaluridae/*genetics/immunology ; Molecular Sequence Data ; Organ Specificity ; Phylogeny ; Protein Structure, Tertiary ; Receptors, Pattern Recognition/*genetics/metabolism ; Sequence Analysis, DNA ; }, abstract = {Innate immune system plays a significant role in all multicellular organisms. The key feature of the system is its ability to recognize and respond to invading microorganisms. Vertebrates including teleost fish have evolved an array of pathogen recognition receptors (PRRs) for detecting and responding to various pathogen-associated molecular patterns (PAMPs), including Toll-like receptors (TLRs), nucleotide-binding domain, leucine-rich repeat containing receptors (NLRs), and the retinoic acid inducible gene I (RIG-I) like receptors (RLRs). In this study, we identified 22 NLRs including six members of the NLR-A subfamily (NODs), two members of the NLR-B subfamily, 11 members of the NLR-C subfamily, and three genes that do not belong to any of these three subfamilies: Apaf1, CIITA, and NACHT-P1. Phylogenetic analysis indicated that orthologs of the mammalian NOD1, NOD2, NOD3, NOD4, and NOD5 were all identified in catfish. In addition, an additional truncated NOD3-like gene was also identified in catfish. While the identities of subfamily A NLRs could be established, the identities of the NLR-B and NLR-C subfamilies were inconclusive at present. Expression of representative NLR genes was analyzed using RT-PCR and qRT-PCR. In healthy catfish tissues, all the tested NLR genes were found to be ubiquitously expressed in all 11 tested catfish tissues. Analysis of expression of these representative NLR genes after bacterial infection with Edwardsiella ictaluri revealed a significant up-regulation of all tested genes in the spleen and liver, but a significant down-regulation in the intestine and head kidney, suggesting their involvement in the immune responses of catfish against the intracellular bacterial pathogen in a tissue-specific manner. The up-regulation and down-regulation of the tested genes exhibited an amazing similarity of expression profiles after infection, suggesting the co-regulation of these genes.}, } @article {pmid22194575, year = {2011}, author = {Huldtgren, T and Cunningham, JA and Yin, C and Stampanoni, M and Marone, F and Donoghue, PC and Bengtson, S}, title = {Fossilized nuclei and germination structures identify Ediacaran "animal embryos" as encysting protists.}, journal = {Science (New York, N.Y.)}, volume = {334}, number = {6063}, pages = {1696-1699}, doi = {10.1126/science.1209537}, pmid = {22194575}, issn = {1095-9203}, mesh = {Animals ; Biological Evolution ; Cell Division ; Cell Nucleus/*ultrastructure ; Cell Shape ; China ; Embryo, Nonmammalian ; Eukaryota/classification/cytology/*growth & development/ultrastructure ; *Fossils ; Imaging, Three-Dimensional ; Life Cycle Stages ; Mesomycetozoea/classification/cytology/growth & development ; Phylogeny ; Synchrotrons ; Tomography, X-Ray ; }, abstract = {Globular fossils showing palintomic cell cleavage in the Ediacaran Doushantuo Formation, China, are widely regarded as embryos of early metazoans, although metazoan synapomorphies, tissue differentiation, and associated juveniles or adults are lacking. We demonstrate using synchrotron-based x-ray tomographic microscopy that the fossils have features incompatible with multicellular metazoan embryos. The developmental pattern is comparable with nonmetazoan holozoans, including germination stages that preclude postcleavage embryology characteristic of metazoans. We conclude that these fossils are neither animals nor embryos. They belong outside crown-group Metazoa, within total-group Holozoa (the sister clade to Fungi that includes Metazoa, Choanoflagellata, and Mesomycetozoea) or perhaps on even more distant branches in the eukaryote tree. They represent an evolutionary grade in which palintomic cleavage served the function of producing propagules for dispersion.}, } @article {pmid22194470, year = {2012}, author = {Li, L and Tibiche, C and Fu, C and Kaneko, T and Moran, MF and Schiller, MR and Li, SS and Wang, E}, title = {The human phosphotyrosine signaling network: evolution and hotspots of hijacking in cancer.}, journal = {Genome research}, volume = {22}, number = {7}, pages = {1222-1230}, pmid = {22194470}, issn = {1549-5469}, support = {R01 GM079689/GM/NIGMS NIH HHS/United States ; /CAPMC/CIHR/Canada ; }, mesh = {Animals ; Cell Communication ; Cell Membrane/genetics/metabolism ; Cytoplasm/genetics/metabolism ; *Evolution, Molecular ; Humans ; Models, Genetic ; Neoplasms/genetics/*metabolism ; Organ Specificity ; Phosphorylation ; Phosphotyrosine/classification/genetics/*metabolism ; Phylogeny ; Protein Binding ; Protein-Tyrosine Kinases/genetics/metabolism ; *Signal Transduction ; src Homology Domains ; }, abstract = {Phosphotyrosine (pTyr) signaling, which plays a central role in cell-cell and cell-environment interactions, has been considered to be an evolutionary innovation in multicellular metazoans. However, neither the emergence nor the evolution of the human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each of which consists of a TK writer, a kinase substrate, and a related reader, such as Src homology (SH) 2 domains and pTyr-binding (PTB) domains, comprise the core machinery of the pTyr signaling network. In this study, we analyzed the evolutionary trajectories of 583 literature-derived and 50,000 computationally predicted human TK circuits in 19 representative eukaryotic species and assigned their evolutionary origins. We found that human TK circuits for intracellular pTyr signaling originated largely from primitive organisms, whereas the inter- or extracellular signaling circuits experienced significant expansion in the bilaterian lineage through the "back-wiring" of newly evolved kinases to primitive substrates and SH2/PTB domains. Conversely, the TK circuits that are involved in tissue-specific signaling evolved mainly in vertebrates by the back-wiring of vertebrate substrates to primitive kinases and SH2/PTB domains. Importantly, we found that cancer signaling preferentially employs the pTyr sites, which are linked to more TK circuits. Our work provides insights into the evolutionary paths of the human pTyr signaling circuits and suggests the use of a network approach for cancer intervention through the targeting of key pTyr sites and their associated signaling hubs in the network.}, } @article {pmid22152105, year = {2011}, author = {Chen, CH and Lin, HY and Pan, CL and Chen, FC}, title = {The genomic features that affect the lengths of 5' untranslated regions in multicellular eukaryotes.}, journal = {BMC bioinformatics}, volume = {12 Suppl 9}, number = {Suppl 9}, pages = {S3}, pmid = {22152105}, issn = {1471-2105}, mesh = {*5' Untranslated Regions ; Animals ; Base Composition ; Codon, Terminator ; Genetic Variation ; Genome ; Genomics ; Humans ; Mice ; Open Reading Frames ; Rats ; }, abstract = {BACKGROUND: The lengths of 5'UTRs of multicellular eukaryotes have been suggested to be subject to stochastic changes, with upstream start codons (uAUGs) as the major constraint to suppress 5'UTR elongation. However, this stochastic model cannot fully explain the variations in 5'UTR length. We hypothesize that the selection pressure on a combination of genomic features is also important for 5'UTR evolution. The ignorance of these features may have limited the explanatory power of the stochastic model. Furthermore, different selective constraints between vertebrates and invertebrates may lead to differences in the determinants of 5'UTR length, which have not been systematically analyzed.

METHODS: Here we use a multiple linear regression model to delineate the correlation between 5'UTR length and the combination of a series of genomic features (G+C content, observed-to-expected (OE) ratios of uAUGs, upstream stop codons (uSTOPs), methylation-related CG/UG dinucleotides, and mRNA-destabilizing UU/UA dinucleotides) in six vertebrates (human, mouse, rat, chicken, African clawed frog, and zebrafish) and four invertebrates (fruit fly, mosquito, sea squirt, and nematode). The relative contributions of each feature to the variation of 5'UTR length were also evaluated.

RESULTS: We found that 14%~33% of the 5'UTR length variations can be explained by a linear combination of the analyzed genomic features. The most important genomic features are the OE ratios of uSTOPs and G+C content. The surprisingly large weightings of uSTOPs highlight the importance of selection on upstream open reading frames (which include both uAUGs and uSTOPs), rather than on uAUGs per se. Furthermore, G+C content is the most important determinants for most invertebrates, but for vertebrates its effect is second to uSTOPs. We also found that shorter 5'UTRs are affected more by the stochastic process, whereas longer 5'UTRs are affected more by selection pressure on genomic features.

CONCLUSIONS: Our results suggest that upstream open reading frames may be the real target of selection, rather than uAUGs. We also show that the selective constraints on genomic features of 5'UTRs differ between vertebrates and invertebrates, and between longer and shorter 5'UTRs. A more comprehensive model that takes these findings into consideration is needed to better explain 5'UTR length evolution.}, } @article {pmid22151646, year = {2011}, author = {Lv, J and Havlak, P and Putnam, NH}, title = {Constraints on genes shape long-term conservation of macro-synteny in metazoan genomes.}, journal = {BMC bioinformatics}, volume = {12 Suppl 9}, number = {Suppl 9}, pages = {S11}, pmid = {22151646}, issn = {1471-2105}, mesh = {Animals ; Chromosomes ; *Evolution, Molecular ; Genetic Linkage ; *Genome ; Humans ; Invertebrates/genetics ; *Models, Genetic ; Software ; *Synteny ; }, abstract = {BACKGROUND: Many metazoan genomes conserve chromosome-scale gene linkage relationships ("macro-synteny") from the common ancestor of multicellular animal life 1234, but the biological explanation for this conservation is still unknown. Double cut and join (DCJ) is a simple, well-studied model of neutral genome evolution amenable to both simulation and mathematical analysis 5, but as we show here, it is not sufficent to explain long-term macro-synteny conservation.

RESULTS: We examine a family of simple (one-parameter) extensions of DCJ to identify models and choices of parameters consistent with the levels of macro- and micro-synteny conservation observed among animal genomes. Our software implements a flexible strategy for incorporating genomic context into the DCJ model to incorporate various types of genomic context ("DCJ-[C]"), and is available as open source software from http://github.com/putnamlab/dcj-c.

CONCLUSIONS: A simple model of genome evolution, in which DCJ moves are allowed only if they maintain chromosomal linkage among a set of constrained genes, can simultaneously account for the level of macro-synteny conservation and for correlated conservation among multiple pairs of species. Simulations under this model indicate that a constraint on approximately 7% of metazoan genes is sufficient to constrain genome rearrangement to an average rate of 25 inversions and 1.7 translocations per million years.}, } @article {pmid22174671, year = {2011}, author = {Reece, SE and Pollitt, LC and Colegrave, N and Gardner, A}, title = {The meaning of death: evolution and ecology of apoptosis in protozoan parasites.}, journal = {PLoS pathogens}, volume = {7}, number = {12}, pages = {e1002320}, pmid = {22174671}, issn = {1553-7374}, support = {/WT_/Wellcome Trust/United Kingdom ; 095831/WT_/Wellcome Trust/United Kingdom ; WT082234MA/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Apoptosis/*physiology ; *Biological Evolution ; Ecosystem ; *Evolution, Molecular ; Host-Parasite Interactions/*physiology ; Plasmodium/cytology/*genetics ; }, abstract = {The discovery that an apoptosis-like, programmed cell death (PCD) occurs in a broad range of protozoan parasites offers novel therapeutic tools to treat some of the most serious infectious diseases of humans, companion animals, wildlife, and livestock. Whilst apoptosis is an essential part of normal development, maintenance, and defence in multicellular organisms, its occurrence in unicellular parasites appears counter-intuitive and has proved highly controversial: according to the Darwinian notion of "survival of the fittest", parasites are expected to evolve strategies to maximise their proliferation, not death. The prevailing, and untested, opinion in the literature is that parasites employ apoptosis to "altruistically" self-regulate the intensity of infection in the host/vector. However, evolutionary theory tells us that at most, this can only be part of the explanation, and other non-mutually exclusive hypotheses must also be tested. Here, we explain the evolutionary concepts that can explain apoptosis in unicellular parasites, highlight the key questions, and outline the approaches required to resolve the controversy over whether parasites "commit suicide". We highlight the need for integration of proximate and functional approaches into an evolutionary framework to understand apoptosis in unicellular parasites. Understanding how, when, and why parasites employ apoptosis is central to targeting this process with interventions that are sustainable in the face of parasite evolution.}, } @article {pmid22174251, year = {2011}, author = {Kuzdzal-Fick, JJ and Fox, SA and Strassmann, JE and Queller, DC}, title = {High relatedness is necessary and sufficient to maintain multicellularity in Dictyostelium.}, journal = {Science (New York, N.Y.)}, volume = {334}, number = {6062}, pages = {1548-1551}, doi = {10.1126/science.1213272}, pmid = {22174251}, issn = {1095-9203}, mesh = {*Biological Evolution ; Clone Cells/cytology ; Dictyostelium/*cytology/genetics/*physiology ; Models, Biological ; Mutation ; Reproduction ; Spores, Protozoan ; }, abstract = {Most complex multicellular organisms develop clonally from a single cell. This should limit conflicts between cell lineages that could threaten the extensive cooperation of cells within multicellular bodies. Cellular composition can be manipulated in the social amoeba Dictyostelium discoideum, which allows us to test and confirm the two key predictions of this theory. Experimental evolution at low relatedness favored cheating mutants that could destroy multicellular development. However, under high relatedness, the forces of mutation and within-individual selection are too small for these destructive cheaters to spread, as shown by a mutation accumulation experiment. Thus, we conclude that the single-cell bottleneck is a powerful stabilizer of cellular cooperation in multicellular organisms.}, } @article {pmid22170053, year = {2012}, author = {Hitomi, K and Arvai, AS and Yamamoto, J and Hitomi, C and Teranishi, M and Hirouchi, T and Yamamoto, K and Iwai, S and Tainer, JA and Hidema, J and Getzoff, ED}, title = {Eukaryotic class II cyclobutane pyrimidine dimer photolyase structure reveals basis for improved ultraviolet tolerance in plants.}, journal = {The Journal of biological chemistry}, volume = {287}, number = {15}, pages = {12060-12069}, pmid = {22170053}, issn = {1083-351X}, support = {R01 GM037684/GM/NIGMS NIH HHS/United States ; R01 GM046312/GM/NIGMS NIH HHS/United States ; GM046312/GM/NIGMS NIH HHS/United States ; GM37684/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Base Sequence ; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; DNA/chemistry ; DNA Repair ; Deoxyribodipyrimidine Photo-Lyase/*chemistry/genetics ; Electrophoretic Mobility Shift Assay ; Flavin-Adenine Dinucleotide/chemistry ; Hydrogen Bonding ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oryza/*enzymology/genetics ; Phosphorylation ; Phylogeny ; Plant Proteins/*chemistry/genetics ; Polymorphism, Genetic ; Protein Binding ; Structural Homology, Protein ; Surface Properties ; Ultraviolet Rays ; }, abstract = {Ozone depletion increases terrestrial solar ultraviolet B (UV-B; 280-315 nm) radiation, intensifying the risks plants face from DNA damage, especially covalent cyclobutane pyrimidine dimers (CPD). Without efficient repair, UV-B destroys genetic integrity, but plant breeding creates rice cultivars with more robust photolyase (PHR) DNA repair activity as an environmental adaptation. So improved strains of Oryza sativa (rice), the staple food for Asia, have expanded rice cultivation worldwide. Efficient light-driven PHR enzymes restore normal pyrimidines to UV-damaged DNA by using blue light via flavin adenine dinucleotide to break pyrimidine dimers. Eukaryotes duplicated the photolyase gene, producing PHRs that gained functions and adopted activities that are distinct from those of prokaryotic PHRs yet are incompletely understood. Many multicellular organisms have two types of PHR: (6-4) PHR, which structurally resembles bacterial CPD PHRs but recognizes different substrates, and Class II CPD PHR, which is remarkably dissimilar in sequence from bacterial PHRs despite their common substrate. To understand the enigmatic DNA repair mechanisms of PHRs in eukaryotic cells, we determined the first crystal structure of a eukaryotic Class II CPD PHR from the rice cultivar Sasanishiki. Our 1.7 Å resolution PHR structure reveals structure-activity relationships in Class II PHRs and tuning for enhanced UV tolerance in plants. Structural comparisons with prokaryotic Class I CPD PHRs identified differences in the binding site for UV-damaged DNA substrate. Convergent evolution of both flavin hydrogen bonding and a Trp electron transfer pathway establish these as critical functional features for PHRs. These results provide a paradigm for light-dependent DNA repair in higher organisms.}, } @article {pmid22167750, year = {2012}, author = {Issazadeh-Navikas, S}, title = {NKT cell self-reactivity: evolutionary master key of immune homeostasis?.}, journal = {Journal of molecular cell biology}, volume = {4}, number = {2}, pages = {70-78}, doi = {10.1093/jmcb/mjr035}, pmid = {22167750}, issn = {1759-4685}, mesh = {Animals ; *Biological Evolution ; Cell Lineage ; *Homeostasis ; Humans ; Immune System/*cytology/immunology ; Natural Killer T-Cells/*cytology/immunology ; }, abstract = {Complex immune responses have evolved to protect multicellular organisms against the invasion of pathogens. This has exerted strong developmental pressure for specialized functions that can also limit damage to self-tissue. Two arms of immunity, the innate and adaptive immune systems, have evolved for quick, non-specific immune responses to pathogens and more efficient, long-lasting ones upon specific recognition of recurrent pathogens. Specialized cells have arisen as the sentinels of these functions, including macrophages, natural killer (NK), and T and B-lymphocytes. Interestingly, a population of immune cells that can exert both of these complex functions, NKT cells, not only share common functions but also exhibit shared cell surface markers of cells of both arms of the immune system. These features, in combination with sophisticated maintenance of immune homeostasis, will be discussed. The recent finding of self-peptide reactivity of NKT cells in the context of CD1d, with capacity to regulate multiple autoimmune and inflammatory conditions, motivates the current proposal that self-reactive NKT cells might be the ancestral link between present NK and T cells. Their parallel selection through evolution by higher vertebrates could be related to their central function as master regulators of immune homeostasis that in part is shared with regulatory T cells. Hypothetical views on how self-reactive NKT cells secure such a central role will also be proposed.}, } @article {pmid22158952, year = {2012}, author = {Ispolatov, I and Ackermann, M and Doebeli, M}, title = {Division of labour and the evolution of multicellularity.}, journal = {Proceedings. Biological sciences}, volume = {279}, number = {1734}, pages = {1768-1776}, pmid = {22158952}, issn = {1471-2954}, mesh = {*Biological Evolution ; *Cell Aggregation ; Cooperative Behavior ; Cyanobacteria/*cytology/physiology ; *Models, Biological ; Phenotype ; Volvox/*cytology/physiology ; }, abstract = {Understanding the emergence and evolution of multicellularity and cellular differentiation is a core problem in biology. We develop a quantitative model that shows that a multicellular form emerges from genetically identical unicellular ancestors when the compartmentalization of poorly compatible physiological processes into component cells of an aggregate produces a fitness advantage. This division of labour between the cells in the aggregate occurs spontaneously at the regulatory level owing to mechanisms present in unicellular ancestors and does not require any genetic predisposition for a particular role in the aggregate or any orchestrated cooperative behaviour of aggregate cells. Mathematically, aggregation implies an increase in the dimensionality of phenotype space that generates a fitness landscape with new fitness maxima, in which the unicellular states of optimized metabolism become fitness saddle points. Evolution of multicellularity is modelled as evolution of a hereditary parameter: the propensity of cells to stick together, which determines the fraction of time a cell spends in the aggregate form. Stickiness can increase evolutionarily owing to the fitness advantage generated by the division of labour between cells in an aggregate.}, } @article {pmid22156033, year = {2011}, author = {Cristea, A and Neagu, A and Sofonea, V}, title = {Lattice Boltzmann simulations of the time evolution of living multicellular systems.}, journal = {Biorheology}, volume = {48}, number = {3-4}, pages = {185-197}, doi = {10.3233/BIR-2011-0595}, pmid = {22156033}, issn = {1878-5034}, mesh = {Animals ; *Biological Evolution ; Cell Aggregation ; Computer Simulation ; Developmental Biology ; Humans ; *Models, Biological ; *Morphogenesis ; Time Factors ; *Tissue Engineering ; }, abstract = {Embryonic tissues and multicellular aggregates of adult cells mimic the behavior of highly viscous liquids. The liquid analogy helps to understand morphogenetic phenomena, such as cell sorting and tissue fusion, observed in developmental biology and tissue engineering. Tissue fusion is vital in tissue printing, an emergent technique based on computer-controlled deposition of tissue fragments and biocompatible materials. Computer simulations proved useful in predicting post-printing shape changes of tissue constructs. The simulation methods available to date, however, are unable to describe the time evolution of living systems made of millions of cells. The Lattice Boltzmann (LB) approach allows the implementation of interaction forces between the constituents of the system and yields time evolution in terms of distribution functions. With tissue engineering applications in mind, we have developed a finite difference Lattice Boltzmann model of a multicellular system and applied it to simulate the sidewise fusion of two contiguous cylinders made of cohesive cells and embedded in a medium (hydrogel). We have identified a biologically relevant range of model parameters. The proposed LB model may be extended to describe the time evolution of more complex multicellular structures such as sheets or tubes produced by tissue printing.}, } @article {pmid22155787, year = {2011}, author = {Liu, BA and Shah, E and Jablonowski, K and Stergachis, A and Engelmann, B and Nash, PD}, title = {The SH2 domain-containing proteins in 21 species establish the provenance and scope of phosphotyrosine signaling in eukaryotes.}, journal = {Science signaling}, volume = {4}, number = {202}, pages = {ra83}, pmid = {22155787}, issn = {1937-9145}, support = {T32 GM007183/GM/NIGMS NIH HHS/United States ; TG-GM07183/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Binding Sites/genetics ; Eukaryota/*genetics/*physiology ; Evolution, Molecular ; Gene Duplication ; Humans ; Models, Molecular ; Molecular Sequence Data ; Phosphotyrosine/*physiology ; Phylogeny ; Protein-Tyrosine Kinases/chemistry/genetics/physiology ; RNA Splice Sites ; Sequence Homology, Amino Acid ; Signal Transduction/genetics/physiology ; Species Specificity ; Systems Biology ; src Homology Domains/*genetics/*physiology ; }, abstract = {The Src homology 2 (SH2) domains are participants in metazoan signal transduction, acting as primary mediators for regulated protein-protein interactions with tyrosine-phosphorylated substrates. Here, we describe the origin and evolution of SH2 domain proteins by means of sequence analysis from 21 eukaryotic organisms from the basal unicellular eukaryotes, where SH2 domains first appeared, through the multicellular animals and increasingly complex metazoans. On the basis of our results, SH2 domains and phosphotyrosine signaling emerged in the early Unikonta, and the numbers of SH2 domains expanded in the choanoflagellate and metazoan lineages with the development of tyrosine kinases, leading to rapid elaboration of phosphotyrosine signaling in early multicellular animals. Our results also indicated that SH2 domains coevolved and the number of the domains expanded alongside protein tyrosine kinases and tyrosine phosphatases, thereby coupling phosphotyrosine signaling to downstream signaling networks. Gene duplication combined with domain gain or loss produced novel SH2-containing proteins that function within phosphotyrosine signaling, which likely have contributed to diversity and complexity in metazoans. We found that intra- and intermolecular interactions within and between SH2 domain proteins increased in prevalence along with organismal complexity and may function to generate more highly connected and robust phosphotyrosine signaling networks.}, } @article {pmid22155583, year = {2012}, author = {Delwart, E and Li, L}, title = {Rapidly expanding genetic diversity and host range of the Circoviridae viral family and other Rep encoding small circular ssDNA genomes.}, journal = {Virus research}, volume = {164}, number = {1-2}, pages = {114-121}, pmid = {22155583}, issn = {1872-7492}, support = {R01 HL105770/HL/NHLBI NIH HHS/United States ; HL105770/HL/NHLBI NIH HHS/United States ; R01 HL083254-04/HL/NHLBI NIH HHS/United States ; R01 HL083254/HL/NHLBI NIH HHS/United States ; R01 HL105770-01/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Circoviridae/*classification/genetics/isolation & purification/*pathogenicity ; DNA Helicases/genetics ; DNA, Circular/genetics ; DNA, Single-Stranded/genetics ; DNA, Viral/*genetics ; Environmental Microbiology ; Gene Order ; *Genetic Variation ; *Genome, Viral ; *Host Specificity ; Humans ; Plants ; Trans-Activators/genetics ; Viral Proteins/genetics ; }, abstract = {The genomes of numerous circoviruses and distantly related circular ssDNA viruses encoding a rolling circle replication initiator protein (Rep) have been characterized from the tissues of mammals, fish, insects, plants (geminivirus and nanovirus), in human and animal feces, in an algae cell, and in diverse environmental samples. We review the genome organization, phylogenetic relationships and initial prevalence studies of cycloviruses, a proposed new genus in the Circoviridae family. Viral fossil rep sequences were also recently identified integrated on the chromosomes of mammals, frogs, lancelets, crustaceans, mites, gastropods, roundworms, placozoans, hydrozoans, protozoans, land plants, fungi, algae, and phytoplasma bacterias and their plasmids, reflecting the very wide past host range of rep bearing viruses. An ancient origin for viruses with Rep-encoding small circular ssDNA genomes, predating the diversification of eukaryotes, is discussed. The cellular hosts and pathogenicity of many recently described rep-containing circular ssDNA genomes remain to be determined. Future studies of the virome of single cell and multi-cellular eukaryotes are likely to further extend the known diversity and host-range of small rep-containing circular ssDNA viral genomes.}, } @article {pmid22144884, year = {2011}, author = {Werner, B and Dingli, D and Lenaerts, T and Pacheco, JM and Traulsen, A}, title = {Dynamics of mutant cells in hierarchical organized tissues.}, journal = {PLoS computational biology}, volume = {7}, number = {12}, pages = {e1002290}, pmid = {22144884}, issn = {1553-7358}, mesh = {Cell Differentiation/physiology ; Cell Growth Processes/physiology ; Colon/cytology ; Computer Simulation ; Epidermal Cells ; Hematopoiesis/physiology ; Humans ; *Models, Biological ; *Mutation ; Stem Cells/*cytology ; Stochastic Processes ; }, abstract = {Most tissues in multicellular organisms are maintained by continuous cell renewal processes. However, high turnover of many cells implies a large number of error-prone cell divisions. Hierarchical organized tissue structures with stem cell driven cell differentiation provide one way to prevent the accumulation of mutations, because only few stem cells are long lived. We investigate the deterministic dynamics of cells in such a hierarchical multi compartment model, where each compartment represents a certain stage of cell differentiation. The dynamics of the interacting system is described by ordinary differential equations coupled across compartments. We present analytical solutions for these equations, calculate the corresponding extinction times and compare our results to individual based stochastic simulations. Our general compartment structure can be applied to different tissues, as for example hematopoiesis, the epidermis, or colonic crypts. The solutions provide a description of the average time development of stem cell and non stem cell driven mutants and can be used to illustrate general and specific features of the dynamics of mutant cells in such hierarchically structured populations. We illustrate one possible application of this approach by discussing the origin and dynamics of PIG-A mutant clones that are found in the bloodstream of virtually every healthy adult human. From this it is apparent, that not only the occurrence of a mutant but also the compartment of origin is of importance.}, } @article {pmid22138219, year = {2012}, author = {Tan, LA and Chand, D and De Almeida, R and Xu, M and De Lannoy, L and Lovejoy, DA}, title = {Modulation of neuroplastic changes and corticotropin-releasing factor-associated behavior by a phylogenetically ancient and conserved peptide family.}, journal = {General and comparative endocrinology}, volume = {176}, number = {3}, pages = {309-313}, doi = {10.1016/j.ygcen.2011.11.011}, pmid = {22138219}, issn = {1095-6840}, mesh = {Corticotropin-Releasing Hormone/genetics/*physiology ; Cytoskeleton/physiology ; *Evolution, Molecular ; Humans ; Neuronal Plasticity/genetics/*physiology ; Phylogeny ; Stress, Physiological/genetics/*physiology ; }, abstract = {The co-evolution of peptides and early cells some 3.7 billion years ago provided bioactive peptides with a long history for the proliferation and refinement of peptide hormones. Central to the adaptation and evolution of cell types in metazoans is the development of peptide signaling systems that regulate stress mechanisms. The corticotropin-releasing factor (CRF) family of peptides represents the canonical family of peptides that are pivotal to the regulation of stress in vertebrates. However, these peptides appear to have evolved at least 2 billion years after the formation of the first postulated bioactive peptides, suggesting that before this, other peptide systems played a role in stress and energy metabolism. The teneurin C-terminal associated peptides (TCAPs) are a recently discovered family of highly conserved peptides that are processed from the teneurin transmembrane proteins. This peptide/protein system is ubiquitous in multicellular organisms and evolved before the CRF family. TCAP-1 is a potent regulator of CRF-associated physiology and behavior and may play a significant role in the regulation of cell-to-cell communication and neuroplasticity in neurons.}, } @article {pmid23705033, year = {2011}, author = {Casás-Selves, M and Degregori, J}, title = {How cancer shapes evolution, and how evolution shapes cancer.}, journal = {Evolution}, volume = {4}, number = {4}, pages = {624-634}, pmid = {23705033}, issn = {1936-6426}, support = {R01 CA157850/CA/NCI NIH HHS/United States ; R01 CA157850-01A1/CA/NCI NIH HHS/United States ; }, abstract = {Evolutionary theories are critical for understanding cancer development at the level of species as well as at the level of cells and tissues, and for developing effective therapies. Animals have evolved potent tumor suppressive mechanisms to prevent cancer development. These mechanisms were initially necessary for the evolution of multi-cellular organisms, and became even more important as animals evolved large bodies and long lives. Indeed, the development and architecture of our tissues were evolutionarily constrained by the need to limit cancer. Cancer development within an individual is also an evolutionary process, which in many respects mirrors species evolution. Species evolve by mutation and selection acting on individuals in a population; tumors evolve by mutation and selection acting on cells in a tissue. The processes of mutation and selection are integral to the evolution of cancer at every step of multistage carcinogenesis, from tumor genesis to metastasis. Factors associated with cancer development, such as aging and carcinogens, have been shown to promote cancer evolution by impacting both mutation and selection processes. While there are therapies that can decimate a cancer cell population, unfortunately, cancers can also evolve resistance to these therapies, leading to the resurgence of treatment-refractory disease. Understanding cancer from an evolutionary perspective can allow us to appreciate better why cancers predominantly occur in the elderly, and why other conditions, from radiation exposure to smoking, are associated with increased cancers. Importantly, the application of evolutionary theory to cancer should engender new treatment strategies that could better control this dreaded disease.}, } @article {pmid22121572, year = {2011}, author = {Markov, MA and Markov, AV}, title = {[Self-organization in the ontogeny of multicellular organisms: a computer simulation].}, journal = {Zhurnal obshchei biologii}, volume = {72}, number = {5}, pages = {323-338}, pmid = {22121572}, issn = {0044-4596}, mesh = {Adaptation, Physiological ; *Artificial Cells/cytology/metabolism ; Biological Evolution ; *Computer Simulation ; Feedback, Physiological ; Gene Regulatory Networks ; Genetic Association Studies ; Genetic Pleiotropy ; Genotype ; *Models, Biological ; Models, Theoretical ; Molecular Mimicry ; *Morphogenesis ; Mutation ; Phenotype ; Software ; }, abstract = {The progress in understanding the patterns of evolution of ontogeny is hindered by the fact that many features of ontogeny are counterintuitive (as well as the features of other processes related to self-organization, self-assembly, and spontaneous increase in complexity). The basic principle of ontogeny of multicellular organisms is that it is the process of self-assembly of ordered multicellular structures by means of coordinated behavior of many individual modules (cells), each of which follows the same set of"rules" encoded in the genome. These rules are based on the genetic regulatory networks. We hypothesize that many specific features of ontogeny that seem nontrivial or enigmatic are, in fact, the inevitable consequences of this basic principle. If so, they do not need special explanations. In order to verify this hypothesis, we developed the computer program "Evo-Devo" based on the above principle. The program is designed to model the self-assembly of ordered multicellular structures from an aggregation of dividing cells that originate from a single original cell (zygote). Each cell follows a set of rules of behavior ("genotype") that can be specified arbitrarily by the experimenter, and is the same for all cells in the embryo (each cell is programmed in exactly the same way as all other cells). It is not allowed to specify rules for groups of cells or for the whole embryo: only local rules that should be followed at the level of a single cell are possible. The analysis of phenotypic implementation of different genotypes revealed several features which are present in the ontogeny of real organisms and are regularly reproduced in the model. These include: inherent stochasticity; inescapable necessity of development of stabilizing adaptations based on negative feedback in order to decrease this stochasticity; equifinality (noise resistance) resulting from these adaptations; the ability of ontogeny to respond to major perturbations by generating new morphological structures that differ from the "normal" ones, but have similar level of complexity; the similarity of phenotypic manifestations of different mutations; channeling of possible evolutionary transformations of ontogeny; Waddington's creodes; high probability of destabilization of ontogeny (e.g., because of mutations); the possibility of a new morphological character to appear initially as a rare anomaly (low penetrance of many mutations); pleiotropy of mutations affecting ontogeny; spontaneous emergence of morphogenetic correlations; integrity of the developing organism. The fact that these features are regularly reproduced in the model implies that they are probably the inevitable consequences of the basic principle of ontogeny of multicellular organisms formulated above.}, } @article {pmid22120468, year = {2011}, author = {Carlson, CA and Kas, A and Kirkwood, R and Hays, LE and Preston, BD and Salipante, SJ and Horwitz, MS}, title = {Decoding cell lineage from acquired mutations using arbitrary deep sequencing.}, journal = {Nature methods}, volume = {9}, number = {1}, pages = {78-80}, pmid = {22120468}, issn = {1548-7105}, support = {T32 HL007093/HL/NHLBI NIH HHS/United States ; DP1OD003278/OD/NIH HHS/United States ; T32HL007093/HL/NHLBI NIH HHS/United States ; R01 CA111582/CA/NCI NIH HHS/United States ; T32 GM007266-38/GM/NIGMS NIH HHS/United States ; R01 DK078340-05/DK/NIDDK NIH HHS/United States ; R01 DK078340/DK/NIDDK NIH HHS/United States ; R01CA111582/CA/NCI NIH HHS/United States ; T32 GM007266/GM/NIGMS NIH HHS/United States ; F30 AG030316/AG/NIA NIH HHS/United States ; F30AG030316/AG/NIA NIH HHS/United States ; R01DK078340/DK/NIDDK NIH HHS/United States ; DP1 OD003278-05/OD/NIH HHS/United States ; R01 CA098243/CA/NCI NIH HHS/United States ; R01CA0982/CA/NCI NIH HHS/United States ; DP1 OD003278/OD/NIH HHS/United States ; T32GM007266/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Lineage/*genetics ; Computer Simulation ; Genome ; High-Throughput Nucleotide Sequencing/*methods ; Mice ; *Mutation ; Phylogeny ; Polymerase Chain Reaction/methods ; Reproducibility of Results ; Sequence Analysis, DNA/*methods ; }, abstract = {Because mutations are inevitable, the genome of each cell in a multicellular organism becomes unique and therefore encodes a record of its ancestry. Here we coupled arbitrary single primer PCR with next-generation DNA sequencing to catalog mutations and deconvolve the phylogeny of cultured mouse cells. This study helps pave the way toward construction of retrospective cell-fate maps based on mutations accumulating in genomes of somatic cells.}, } @article {pmid22120185, year = {2012}, author = {Huang, PJ and Lin, WC and Chen, SC and Lin, YH and Sun, CH and Lyu, PC and Tang, P}, title = {Identification of putative miRNAs from the deep-branching unicellular flagellates.}, journal = {Genomics}, volume = {99}, number = {2}, pages = {101-107}, doi = {10.1016/j.ygeno.2011.11.002}, pmid = {22120185}, issn = {1089-8646}, mesh = {Chromosome Mapping ; Gene Expression Profiling ; Giardia lamblia/*genetics ; High-Throughput Nucleotide Sequencing ; MicroRNAs/*genetics/metabolism ; RNA, Protozoan/*genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Trichomonadida/*genetics ; }, abstract = {MicroRNAs (miRNAs) are a class of extensively studied RNAi-associated small RNAs that play a critical role in eukaryotic gene regulation. However, knowledge on the miRNA and its regulation in unicellular eukaryotes is very limited. In order to obtain a better understanding on the origin of miRNA regulation system, we used deep-sequencing technology to investigate the miRNA expression pattern in four deep-branching unicellular flagellates: Giardia lamblia, Trichomonas vaginalis, Tritrichomonas foetus, and Pentatrichomonas hominis. In addition to the known miRNAs that have been described in G. lamblia and T. vaginalis, we identified 14 ancient animal miRNA families and 13 plant-specific families. Bioinformatics analysis also identified four novel miRNA candidates with reliable precursor structures derived from mature tRNAs. Our results indicated that miRNAs are likely to be a general feature for gene regulation throughout unicellular and multicellular eukaryotes and some of them may derive from unconventional ncRNAs such as snoRNA and tRNA.}, } @article {pmid22120072, year = {2011}, author = {Ding, L and Yan, XC and Sun, XW and Teng, CB}, title = {[Regulation of zebrafish development by microRNAs].}, journal = {Yi chuan = Hereditas}, volume = {33}, number = {11}, pages = {1179-1184}, doi = {10.3724/sp.j.1005.2011.01179}, pmid = {22120072}, issn = {0253-9772}, mesh = {Animals ; Female ; *Gene Expression Regulation, Developmental ; Male ; MicroRNAs/genetics/*metabolism ; Zebrafish/*embryology/genetics/metabolism ; }, abstract = {MicroRNAs (miRNAs) are a class of non-coding small RNAs at the length about 22nt, which are found in the cells of both unicellular and multicellular eukaryotes, and highly conserved in many processes of biological evolution. miRNAs play important roles in the regulation of animal development, physiological functions, and pathological processes. As a model organism, zebrafish has been widely used in the modern biological researches. The studies on miRNAs in zebrafish are capable of revealing the function of miRNAs in vertebrate. This paper reviews the effects of total miRNA deletion and the individual miRNAs on the embryonic development of zebrafish in order to provide the clues for the functional researches of miRNAs on vertebrate and breeding in fish.}, } @article {pmid22106285, year = {2011}, author = {Willmann, R and Lajunen, HM and Erbs, G and Newman, MA and Kolb, D and Tsuda, K and Katagiri, F and Fliegmann, J and Bono, JJ and Cullimore, JV and Jehle, AK and Götz, F and Kulik, A and Molinaro, A and Lipka, V and Gust, AA and Nürnberger, T}, title = {Arabidopsis lysin-motif proteins LYM1 LYM3 CERK1 mediate bacterial peptidoglycan sensing and immunity to bacterial infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {108}, number = {49}, pages = {19824-19829}, pmid = {22106285}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/metabolism/microbiology ; Arabidopsis Proteins/classification/genetics/*metabolism ; Bacteria/growth & development/immunology/*metabolism ; Disease Resistance/genetics/immunology ; Gene Expression Regulation, Plant ; Green Fluorescent Proteins/genetics/metabolism ; Host-Pathogen Interactions/immunology ; Immunoblotting ; Microscopy, Confocal ; Mutation ; Oligonucleotide Array Sequence Analysis ; Peptidoglycan/immunology/*metabolism ; Phylogeny ; Plant Diseases/genetics/immunology/microbiology ; Plants, Genetically Modified ; Protein Serine-Threonine Kinases/genetics/*metabolism ; Pseudomonas syringae/immunology/metabolism/physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Staphylococcus aureus/immunology/metabolism/physiology ; Transcriptome ; }, abstract = {Recognition of microbial patterns by host pattern recognition receptors is a key step in immune activation in multicellular eukaryotes. Peptidoglycans (PGNs) are major components of bacterial cell walls that possess immunity-stimulating activities in metazoans and plants. Here we show that PGN sensing and immunity to bacterial infection in Arabidopsis thaliana requires three lysin-motif (LysM) domain proteins. LYM1 and LYM3 are plasma membrane proteins that physically interact with PGNs and mediate Arabidopsis sensitivity to structurally different PGNs from gram-negative and gram-positive bacteria. lym1 and lym3 mutants lack PGN-induced changes in transcriptome activity patterns, but respond to fungus-derived chitin, a pattern structurally related to PGNs, in a wild-type manner. Notably, lym1, lym3, and lym3 lym1 mutant genotypes exhibit supersusceptibility to infection with virulent Pseudomonas syringae pathovar tomato DC3000. Defects in basal immunity in lym3 lym1 double mutants resemble those observed in lym1 and lym3 single mutants, suggesting that both proteins are part of the same recognition system. We further show that deletion of CERK1, a LysM receptor kinase that had previously been implicated in chitin perception and immunity to fungal infection in Arabidopsis, phenocopies defects observed in lym1 and lym3 mutants, such as peptidoglycan insensitivity and enhanced susceptibility to bacterial infection. Altogether, our findings suggest that plants share with metazoans the ability to recognize bacterial PGNs. However, as Arabidopsis LysM domain proteins LYM1, LYM3, and CERK1 form a PGN recognition system that is unrelated to metazoan PGN receptors, we propose that lineage-specific PGN perception systems have arisen through convergent evolution.}, } @article {pmid22102876, year = {2011}, author = {Ladenburger, EM and Plattner, H}, title = {Calcium-release channels in paramecium. Genomic expansion, differential positioning and partial transcriptional elimination.}, journal = {PloS one}, volume = {6}, number = {11}, pages = {e27111}, pmid = {22102876}, issn = {1932-6203}, mesh = {Alternative Splicing ; Amino Acid Sequence ; Calcium/*metabolism ; Calcium Signaling ; Cell Membrane/metabolism ; *Genomics ; Inositol 1,4,5-Trisphosphate Receptors/*genetics/metabolism ; Molecular Sequence Data ; Organelles/metabolism ; Paramecium tetraurelia/cytology/*genetics/*metabolism ; Phylogeny ; Ryanodine/metabolism ; Ryanodine Receptor Calcium Release Channel/*genetics/metabolism ; Sequence Homology, Amino Acid ; }, abstract = {The release of Ca[2+] from internal stores is a major source of signal Ca[2+] in almost all cell types. The internal Ca[2+] pools are activated via two main families of intracellular Ca[2+]-release channels, the ryanodine and the inositol 1,4,5-trisphosphate (InsP3) receptors. Among multicellular organisms these channel types are ubiquitous, whereas in most unicellular eukaryotes the identification of orthologs is impaired probably due to evolutionary sequence divergence. However, the ciliated protozoan Paramecium allowed us to prognosticate six groups, with a total of 34 genes, encoding proteins with characteristics typical of InsP3 and ryanodine receptors by BLAST search of the Paramecium database. We here report that these Ca[2+]-release channels may display all or only some of the characteristics of canonical InsP3 and ryanodine receptors. In all cases, prediction methods indicate the presence of six trans-membrane regions in the C-terminal domains, thus corresponding to canonical InsP3 receptors, while a sequence homologous to the InsP3-binding domain is present only in some types. Only two types have been analyzed in detail previously. We now show, by using antibodies and eventually by green fluorescent protein labeling, that the members of all six groups localize to distinct organelles known to participate in vesicle trafficking and, thus, may provide Ca[2+] for local membrane-membrane interactions. Whole genome duplication can explain radiation within the six groups. Comparative and evolutionary evaluation suggests derivation from a common ancestor of canonical InsP3 and ryanodine receptors. With one group we could ascertain, to our knowledge for the first time, aberrant splicing in one thoroughly analyzed Paramecium gene. This yields truncated forms and, thus, may indicate a way to pseudogene formation. No comparable analysis is available for any other, free-living or parasitic/pathogenic protozoan.}, } @article {pmid22096484, year = {2011}, author = {Liu, X and Song, Y and Lu, H and Tang, B and Piao, X and Hou, N and Peng, S and Jiang, N and Yin, J and Liu, M and Chen, Q}, title = {Transcriptome of small regulatory RNAs in the development of the zoonotic parasite Trichinella spiralis.}, journal = {PloS one}, volume = {6}, number = {11}, pages = {e26448}, pmid = {22096484}, issn = {1932-6203}, mesh = {Animals ; Base Sequence ; MicroRNAs/*genetics ; Molecular Sequence Data ; RNA, Helminth/*genetics ; RNA, Small Interfering/*genetics ; Sequence Analysis, RNA ; Trichinella spiralis/*genetics ; }, abstract = {BACKGROUND: Trichinella spiralis is a parasite with unique features. It is a multicellular organism but with an intracellular parasitization and development stage. T. spiralis is the helminthic pathogen that causes zoonotic trichinellosis and afflicts more than 10 million people worldwide, whereas the parasite's biology, especially the developmental regulation is largely unknown. In other organisms, small non-coding RNAs, such as microRNAs (miRNA) and small interfering RNAs (siRNA) execute post-transcriptional regulation by translational repression or mRNA degradation, and a large number of miRNAs have been identified in diverse species. In T. spiralis, the profile of small non-coding RNAs and their function remains poorly understood.

Here, the transcriptional profiles of miRNA and siRNA in three developmental stages of T. spiralis in the rat host were investigated, and compared by high-throughput cDNA sequencing technique ("RNA-seq"). 5,443,641 unique sequence tags were obtained. Of these, 21 represented conserved miRNAs related to 13 previously identified metazoan miRNA families and 213 were novel miRNAs so far unique to T. spiralis. Some of these miRNAs exhibited stage-specific expression. Expression of miRNAs was confirmed in three stages of the life cycle by qRT-PCR and northern blot analysis. In addition, endogenous siRNAs (endo-siRNAs) were found mainly derived from natural antisense transcripts (NAT) and transposable elements (TE) in the parasite.

CONCLUSIONS AND SIGNIFICANCE: We provide evidence for the presence of miRNAs and endo-siRNAs in T. spiralis. The miRNAs accounted for the major proportion of the small regulatory RNA population of T. spiralis, while fewer endogenous siRNAs were found. The finding of stage-specific expression patterns of the miRNAs in different developmental stages of T. spiralis suggests that miRNAs may play important roles in parasite development. Our data provide a basis for further understanding of the molecular regulation and functional evolution of miRNAs in parasitic nematodes.}, } @article {pmid22094562, year = {2011}, author = {Montanaro, L and Poggi, A and Visai, L and Ravaioli, S and Campoccia, D and Speziale, P and Arciola, CR}, title = {Extracellular DNA in biofilms.}, journal = {The International journal of artificial organs}, volume = {34}, number = {9}, pages = {824-831}, doi = {10.5301/ijao.5000051}, pmid = {22094562}, issn = {1724-6040}, mesh = {Animals ; Apoptosis ; Bacterial Infections/genetics/immunology/*microbiology ; *Bacteriolysis ; Biofilms/*growth & development ; DNA, Bacterial/immunology/*metabolism ; *Gene Transfer, Horizontal ; Humans ; Immunity, Innate ; Inflammation/immunology/microbiology ; Phagocytosis ; Quorum Sensing ; }, abstract = {Extracellular DNA (eDNA) is an important biofilm component that was recently discovered. Its presence has been initially observed in biofilms of Pseudomonas aeruginosa, Streptococcus intermedius, Streptococcus mutans, then Enterococcus faecalis and staphylococci. Autolysis is the common mechanism by which eDNA is released. In P. aeruginosa eDNA is generated by lysis of a bacterial subpopulation, under control of quorum sensing system. In E. faecalis autolysis proceeds in a fratricide mode, resulting from a process similar to necrosis of eukaryotic cells. In Staphylococcus aureus autolysis originates by an altruistic suicide, i.e., a programmed cell death similar to apoptosis of eukaryotic cells. In S. aureus autolysis is mediated by murein hydrolase, while in S. epidermidis by the autolysin protein AtlE. In P. aeruginosa eDNA is located primarily in the stalks of mushroom-shaped multicellular structures. In S. aureus the crucial role of eDNA in stabilizing biofilm is highlighted by the disgregating effect of DNase I. eDNA represents an important mechanism for horizontal gene transfer in bacteria. eDNA and other microbial structural motifs are recognized by the innate immune system via the TLR family of pattern recognition receptors (PRRs).}, } @article {pmid22094428, year = {2012}, author = {Rashidi, A and Kirkwood, TB and Shanley, DP}, title = {Evolution of asymmetric damage segregation : a modelling approach.}, journal = {Sub-cellular biochemistry}, volume = {57}, number = {}, pages = {315-330}, doi = {10.1007/978-94-007-2561-4_14}, pmid = {22094428}, issn = {0306-0225}, support = {BB/C008200/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Aging/genetics/*metabolism/pathology ; Candida albicans/genetics/growth & development/*metabolism ; Cell Division ; *Evolution, Molecular ; Gene Expression Regulation, Fungal ; Longevity ; Microbial Viability ; *Models, Biological ; Proteolysis ; Schizosaccharomyces/genetics/growth & development/*metabolism ; Schizosaccharomyces pombe Proteins/genetics/*metabolism ; }, abstract = {Mother cell-specific ageing is a well-known phenomenon in budding yeast Saccharomyces cerevisiae. Asymmetric segregation of damage and its accumulation in the mother cell has been proposed as one important mechanism. There are, however, unicellular organisms such as the fission yeast Schizosaccharomyces pombe, which replicates with almost no asymmetry of segregation of damage and the pathogenic yeast Candida albicans, which falls around the middle of the segregation spectrum far from both complete symmetry and complete asymmetry. The ultimate evolutionary cause that determines the way damage segregates in a given organism is not known. Here we develop a mathematical model to examine the selective forces that drive the evolution of asymmetry and discover the conditions in which symmetry is the optimal strategy. Three main processes are included in the model: protein synthesis (growth), protein damage, and degradation of damage. We consider, for the first time, the costs to the cell that might accompany the evolution of asymmetry and incorporate them into the model along with known trade-offs between reproductive and maintenance investments and their energy requirements. The model provides insight into the relationship between ecology and cellular trade-off physiology in the context of unicellular ageing, and applications of the model may extend to multicellular organisms.}, } @article {pmid22092088, year = {2012}, author = {McCormick, JR and Flärdh, K}, title = {Signals and regulators that govern Streptomyces development.}, journal = {FEMS microbiology reviews}, volume = {36}, number = {1}, pages = {206-231}, pmid = {22092088}, issn = {1574-6976}, support = {R15 GM096268/GM/NIGMS NIH HHS/United States ; R15 GM096268-01/GM/NIGMS NIH HHS/United States ; GM96268/GM/NIGMS NIH HHS/United States ; }, mesh = {*Gene Expression Regulation, Bacterial ; Hyphae/growth & development ; *Signal Transduction ; Spores, Bacterial/growth & development ; Streptomyces coelicolor/cytology/*genetics/*growth & development/metabolism ; }, abstract = {Streptomyces coelicolor is the genetically best characterized species of a populous genus belonging to the gram-positive Actinobacteria. Streptomycetes are filamentous soil organisms, well known for the production of a plethora of biologically active secondary metabolic compounds. The Streptomyces developmental life cycle is uniquely complex and involves coordinated multicellular development with both physiological and morphological differentiation of several cell types, culminating in the production of secondary metabolites and dispersal of mature spores. This review presents a current appreciation of the signaling mechanisms used to orchestrate the decision to undergo morphological differentiation, and the regulators and regulatory networks that direct the intriguing development of multigenomic hyphae first to form specialized aerial hyphae and then to convert them into chains of dormant spores. This current view of S. coelicolor development is destined for rapid evolution as data from '-omics' studies shed light on gene regulatory networks, new genetic screens identify hitherto unknown players, and the resolution of our insights into the underlying cell biological processes steadily improve.}, } @article {pmid22073591, year = {2011}, author = {Tanaka, T}, title = {[Mechanisms of cellular senescence by tumor suppressor p53].}, journal = {Nihon rinsho. Japanese journal of clinical medicine}, volume = {69}, number = {10}, pages = {1891-1900}, pmid = {22073591}, issn = {0047-1852}, mesh = {Animals ; Cell Cycle/physiology ; Cellular Senescence/*physiology ; Energy Metabolism/physiology ; Neoplasm Proteins/*physiology ; Receptors, Cell Surface/*physiology ; }, abstract = {Cellular senescence is a complexity of ageing and cancer biology. As malignant tumors can culminate individuals in life-termination, evolution has provided multicellular organisms with an acquisition of distinctive safety device, cellular senescence, to circumvent the development. Diploid cells, indeed, sense accumulation of hostile stresses such as genomic integrity, metabolic dysfunction and oncogene-induced mitotic signals, leading to activation of cell cycle arrest and/or programmed cell death. A tumor suppressor, p53, has been reported to function as a governing center to defend against these malignant transformations. Here we review how p53 cooperate with adverse stresses to drive cellular senescence, providing a framework for intricate molecular cross-talks.}, } @article {pmid22053856, year = {2011}, author = {Chen, XS and Penny, D and Collins, LJ}, title = {Characterization of RNase MRP RNA and novel snoRNAs from Giardia intestinalis and Trichomonas vaginalis.}, journal = {BMC genomics}, volume = {12}, number = {}, pages = {550}, pmid = {22053856}, issn = {1471-2164}, mesh = {Base Sequence ; Contig Mapping ; Endoribonucleases/*genetics ; Giardia lamblia/*genetics ; Molecular Sequence Data ; Nucleic Acid Conformation ; Protozoan Proteins/*genetics ; RNA Processing, Post-Transcriptional ; RNA, Protozoan/genetics ; RNA, Small Nucleolar/*genetics ; Sequence Analysis, RNA ; Trichomonas vaginalis/*genetics ; }, abstract = {BACKGROUND: Eukaryotic cells possess a complex network of RNA machineries which function in RNA-processing and cellular regulation which includes transcription, translation, silencing, editing and epigenetic control. Studies of model organisms have shown that many ncRNAs of the RNA-infrastructure are highly conserved, but little is known from non-model protists. In this study we have conducted a genome-scale survey of medium-length ncRNAs from the protozoan parasites Giardia intestinalis and Trichomonas vaginalis.

RESULTS: We have identified the previously 'missing' Giardia RNase MRP RNA, which is a key ribozyme involved in pre-rRNA processing. We have also uncovered 18 new H/ACA box snoRNAs, expanding our knowledge of the H/ACA family of snoRNAs.

CONCLUSIONS: Results indicate that Giardia intestinalis and Trichomonas vaginalis, like their distant multicellular relatives, contain a rich infrastructure of RNA-based processing. From here we can investigate the evolution of RNA processing networks in eukaryotes.}, } @article {pmid22045996, year = {2012}, author = {Tucker, RP and Beckmann, J and Leachman, NT and Schöler, J and Chiquet-Ehrismann, R}, title = {Phylogenetic analysis of the teneurins: conserved features and premetazoan ancestry.}, journal = {Molecular biology and evolution}, volume = {29}, number = {3}, pages = {1019-1029}, pmid = {22045996}, issn = {1537-1719}, mesh = {Alternative Splicing ; Animals ; Base Sequence ; Chickens ; Ciona intestinalis ; Cluster Analysis ; Computational Biology ; Conserved Sequence/genetics ; DNA Primers/genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/genetics ; Humans ; Mice ; Molecular Sequence Data ; Multigene Family/*genetics ; Nerve Tissue Proteins/*genetics ; *Phylogeny ; Protein Structure, Tertiary ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Alignment ; Sequence Analysis, DNA ; Species Specificity ; Tenascin/*genetics ; Zebrafish ; }, abstract = {Teneurins are type II transmembrane proteins expressed during pattern formation and neurogenesis with an intracellular domain that can be transported to the nucleus and an extracellular domain that can be shed into the extracellular milieu. In Drosophila melanogaster, Caenorhabditis elegans, and mouse the knockdown or knockout of teneurin expression can lead to abnormal patterning, defasciculation, and abnormal pathfinding of neurites, and the disruption of basement membranes. Here, we have identified and analyzed teneurins from a broad range of metazoan genomes for nuclear localization sequences, protein interaction domains, and furin cleavage sites and have cloned and sequenced the intracellular domains of human and avian teneurins to analyze alternative splicing. The basic organization of teneurins is highly conserved in Bilateria: all teneurins have epidermal growth factor (EGF) repeats, a cysteine-rich domain, and a large region identical in organization to the carboxy-half of prokaryotic YD-repeat proteins. Teneurins were not found in the genomes of sponges, cnidarians, or placozoa, but the choanoflagellate Monosiga brevicollis has a gene encoding a predicted teneurin with a transmembrane domain, EGF repeats, a cysteine-rich domain, and a region homologous to YD-repeat proteins. Further examination revealed that most of the extracellular domain of the M. brevicollis teneurin is encoded on a single huge 6,829-bp exon and that the cysteine-rich domain is similar to sequences found in an enzyme expressed by the diatom Phaeodactylum tricornutum. This leads us to suggest that teneurins are complex hybrid fusion proteins that evolved in a choanoflagellate via horizontal gene transfer from both a prokaryotic gene and a diatom or algal gene, perhaps to improve the capacity of the choanoflagellate to bind to its prokaryotic prey. As choanoflagellates are considered to be the closest living relatives of animals, the expression of a primitive teneurin by an ancestral choanoflagellate may have facilitated the evolution of multicellularity and complex histogenesis in metazoa.}, } @article {pmid22039174, year = {2011}, author = {Rao, Y and Wu, G and Wang, Z and Chai, X and Nie, Q and Zhang, X}, title = {Mutation bias is the driving force of codon usage in the Gallus gallus genome.}, journal = {DNA research : an international journal for rapid publication of reports on genes and genomes}, volume = {18}, number = {6}, pages = {499-512}, pmid = {22039174}, issn = {1756-1663}, mesh = {Animals ; Base Composition ; Chickens/*genetics ; *Codon ; Evolution, Molecular ; Gene Expression Regulation ; *Genome ; *Mutation ; RNA, Transfer/genetics ; Recombination, Genetic ; }, abstract = {Synonymous codons are used with different frequencies both among species and among genes within the same genome and are controlled by neutral processes (such as mutation and drift) as well as by selection. Up to now, a systematic examination of the codon usage for the chicken genome has not been performed. Here, we carried out a whole genome analysis of the chicken genome by the use of the relative synonymous codon usage (RSCU) method and identified 11 putative optimal codons, all of them ending with uracil (U), which is significantly departing from the pattern observed in other eukaryotes. Optimal codons in the chicken genome are most likely the ones corresponding to highly expressed transfer RNA (tRNAs) or tRNA gene copy numbers in the cell. Codon bias, measured as the frequency of optimal codons (Fop), is negatively correlated with the G + C content, recombination rate, but positively correlated with gene expression, protein length, gene length and intron length. The positive correlation between codon bias and protein, gene and intron length is quite different from other multi-cellular organism, as this trend has been only found in unicellular organisms. Our data displayed that regional G + C content explains a large proportion of the variance of codon bias in chicken. Stepwise selection model analyses indicate that G + C content of coding sequence is the most important factor for codon bias. It appears that variation in the G + C content of CDSs accounts for over 60% of the variation of codon bias. This study suggests that both mutation bias and selection contribute to codon bias. However, mutation bias is the driving force of the codon usage in the Gallus gallus genome. Our data also provide evidence that the negative correlation between codon bias and recombination rates in G. gallus is determined mostly by recombination-dependent mutational patterns.}, } @article {pmid22035946, year = {2011}, author = {Umen, JG}, title = {Evolution of sex and mating loci: an expanded view from Volvocine algae.}, journal = {Current opinion in microbiology}, volume = {14}, number = {6}, pages = {634-641}, pmid = {22035946}, issn = {1879-0364}, support = {R01 GM078376-07/GM/NIGMS NIH HHS/United States ; R01 GM078376-02/GM/NIGMS NIH HHS/United States ; R01 GM078376-05/GM/NIGMS NIH HHS/United States ; R01 GM078376-04/GM/NIGMS NIH HHS/United States ; R01 GM078376-06/GM/NIGMS NIH HHS/United States ; R01 GM078376-03/GM/NIGMS NIH HHS/United States ; R01 GM078376/GM/NIGMS NIH HHS/United States ; R01 GM078376-01/GM/NIGMS NIH HHS/United States ; R01 GM078376-04S1/GM/NIGMS NIH HHS/United States ; }, mesh = {*Cell Division ; Chlamydomonas/genetics/*physiology ; DNA, Plant/genetics ; *Evolution, Molecular ; Genetic Variation ; *Recombination, Genetic ; Volvox/genetics/*physiology ; }, abstract = {Sexual reproduction in Volvocine algae coevolved with the acquisition of multicellularity. Unicellular genera such as Chlamydomonas and small colonial genera from this group have classical mating types with equal-sized gametes, while larger multicellular genera such as Volvox have differentiated males and females that produce sperm and eggs respectively. Newly available sequence from the Volvox and Chlamydomonas genomes and mating loci open up the potential to investigate how sex-determining regions co-evolve with major changes in development and sexual reproduction. The expanded size and sequence divergence between the male and female haplotypes of the Volvox mating locus (MT) not only provide insights into how the colonial Volvocine algae might have evolved sexual dimorphism, but also raise questions about why the putative ancestral-like MT locus in Chlamydomonas shows less divergence between haplotypes than expected.}, } @article {pmid22035865, year = {2011}, author = {Xu, W and Ji, JY}, title = {Dysregulation of CDK8 and Cyclin C in tumorigenesis.}, journal = {Journal of genetics and genomics = Yi chuan xue bao}, volume = {38}, number = {10}, pages = {439-452}, pmid = {22035865}, issn = {1673-8527}, support = {P20 RR016456/RR/NCRR NIH HHS/United States ; R01 DK095013/DK/NIDDK NIH HHS/United States ; P20RR016456/RR/NCRR NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Cell Transformation, Neoplastic/*genetics ; Cyclin C/*genetics/metabolism ; Cyclin-Dependent Kinase 8/*genetics/metabolism ; Drosophila melanogaster/*genetics ; *Gene Expression Regulation, Neoplastic ; Humans ; Mediator Complex/genetics ; Molecular Sequence Data ; Neoplasms/*genetics ; Phylogeny ; Protein Conformation ; RNA Polymerase II/genetics ; Transcription, Genetic ; }, abstract = {Appropriately controlled gene expression is fundamental for normal growth and survival of all living organisms. In eukaryotes, the transcription of protein-coding mRNAs is dependent on RNA polymerase II (Pol II). The multi-subunit transcription cofactor Mediator complex is proposed to regulate most, if not all, of the Pol II-dependent transcription. Here we focus our discussion on two subunits of the Mediator complex, cyclin-dependent kinase 8 (CDK8) and its regulatory partner Cyclin C (CycC), because they are either mutated or amplified in a variety of human cancers. CDK8 functions as an oncoprotein in melanoma and colorectal cancers, thus there are considerable interests in developing drugs specifically targeting the CDK8 kinase activity. However, to evaluate the feasibility of targeting CDK8 for cancer therapy and to understand how their dysregulation contributes to tumorigenesis, it is essential to elucidate the in vivo function and regulation of CDK8-CycC, which are still poorly understood in multi-cellular organisms. We summarize the evidence linking their dysregulation to various cancers and present our bioinformatics and computational analyses on the structure and evolution of CDK8. We also discuss the implications of these observations in tumorigenesis. Because most of the Mediator subunits, including CDK8 and CycC, are highly conserved during eukaryotic evolution, we expect that investigations using model organisms such as Drosophila will provide important insights into the function and regulation of CDK8 and CycC in different cellular and developmental contexts.}, } @article {pmid22035724, year = {2011}, author = {Sunderland, ME}, title = {Morphogenesis, Dictyostelium, and the search for shared developmental processes.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {42}, number = {4}, pages = {508-517}, doi = {10.1016/j.shpsc.2011.07.002}, pmid = {22035724}, issn = {1879-2499}, mesh = {Animals ; *Biological Evolution ; Developmental Biology/*history ; *Dictyostelium/growth & development ; History, 20th Century ; Life Cycle Stages ; *Morphogenesis ; }, abstract = {In the 1930s John Tyler Bonner began studying the slime mold, Dictyostelium discoideum, as a way to investigate how organisms develop. With a life cycle that includes periods of unicellularity and multicellularity, Dictyostelium raises questions fundamental to development and evolution. In Morphogenesis: An Essay on Development (1952), Bonner built on his work with Dictyostelium to inform developmental theory and practice. By exploring how Bonner's early work with Dictyostelium motivated his synthetic approach in Morphogenesis, this paper presents an example of how those who studied development sought ways to gain traction in the rapidly changing life sciences. While a biochemical viewpoint of development became dominant, morphogenesis provided a way to reintroduce and emphasize biological organization at the organismal level. Bonner's early work offers a window to mid-twentieth century studies of development, an understudied area in the history of science, and shows that it was a time when growing experimental evidence enabled new ways of thinking about the relationship between ontogeny and evolution, and more broadly, about how the parts of nature might fit together.}, } @article {pmid22028195, year = {2012}, author = {Slyfield, CR and Tkachenko, EV and Wilson, DL and Hernandez, CJ}, title = {Three-dimensional dynamic bone histomorphometry.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {27}, number = {2}, pages = {486-495}, pmid = {22028195}, issn = {1523-4681}, support = {R21 AR054448/AR/NIAMS NIH HHS/United States ; T32 AR007505-22/AR/NIAMS NIH HHS/United States ; R21AR054448/AR/NIAMS NIH HHS/United States ; T32 AR007505/AR/NIAMS NIH HHS/United States ; R21 AR054448-02/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Bone Resorption/pathology/physiopathology ; Bone and Bones/*pathology/physiopathology ; Calcification, Physiologic/physiology ; Female ; Imaging, Three-Dimensional/*methods ; Organ Size ; Osteogenesis ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Surface Properties ; }, abstract = {Dynamic bone histomorphometry is the standard method for measuring bone remodeling at the level of individual events. Although dynamic bone histomorphometry is an invaluable tool for understanding osteoporosis and other metabolic bone diseases, the technique's two-dimensional nature requires the use of stereology and prevents measures of individual remodeling event number and size. Here, we used a novel three-dimensional fluorescence imaging technique to achieve measures of individual resorption cavities and formation events. We performed this three-dimensional histomorphometry approach using a common model of postmenopausal osteoporosis, the ovariectomized rat. The three-dimensional images demonstrated the spatial relationship between resorption cavities and formation events consistent with the hemiosteonal model of cancellous bone remodeling. Established ovariectomy was associated with significant increases in the number of resorption cavities per unit bone surface (2.38 ± 0.24 mm[-2] sham surgery versus 3.86 ± 0.35 mm[-2] bilateral ovariectomy [OVX], mean ± SD, p < 0.05) and total volume occupied by cavities per unit bone volume (0.38% ± 0.06% sham versus 1.12% ± 0.18% OVX, p < 0.001), but there was no difference in surface area per resorption cavity, maximum cavity depth, or cavity volume. In addition, we found that established ovariectomy is associated with increased size of bone formation events because of the merging of formation events (23,700 ± 6,890 µm[2] sham verusus 33,300 ± 7,950 µm[2] OVX). No differences in mineral apposition rate (determined in 3D) were associated with established ovariectomy. That established estrogen depletion is associated with increased number of remodeling events with only subtle changes in remodeling event size suggests that circulating estrogens may have their primary effect on the origination of new basic multicellular units with relatively little effect on the progression and termination of active remodeling events.}, } @article {pmid22024988, year = {2012}, author = {Grippo, PJ and Sandgren, EP}, title = {Acinar-to-ductal metaplasia accompanies c-myc-induced exocrine pancreatic cancer progression in transgenic rodents.}, journal = {International journal of cancer}, volume = {131}, number = {5}, pages = {1243-1248}, doi = {10.1002/ijc.27322}, pmid = {22024988}, issn = {1097-0215}, support = {R01-CA76361/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carcinoma, Acinar Cell/genetics/metabolism/*pathology ; Carcinoma, Pancreatic Ductal/genetics/metabolism/*pathology ; Cell Transformation, Neoplastic/genetics/*pathology ; Disease Progression ; Humans ; Immunoenzyme Techniques ; Keratin-19/genetics ; Metaplasia/genetics/metabolism/*pathology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Pancreas, Exocrine/metabolism/*pathology ; Pancreatic Elastase/genetics ; Pancreatic Neoplasms/genetics/metabolism/*pathology ; Phenotype ; Promoter Regions, Genetic/genetics ; Proto-Oncogene Proteins c-myc/*physiology ; Rats ; }, abstract = {Several important characteristics of exocrine pancreatic tumor pathogenesis remain incompletely defined, including identification of the cell of origin. Most human pancreatic neoplasms are ductal adenocarcinomas. However, acinar cells have been proposed as the source of some ductal neoplasms through a process of acinar-to-ductal metaplasia. The oncogenic transcription factor c-myc is associated with human pancreatic neoplasms. Transgenic mice overexpressing c-myc under control of acinar cell-specific elastase (Ela) gene regulatory elements not only develop acinar cell carcinomas but also mixed neoplasms that display both acinar-like neoplastic cells and duct-like neoplastic cells. In this report, we demonstrate that, first, c-myc is sufficient to induce acinar hyperplasia, though neoplastic lesions develop focally. Second, cell proliferation remains elevated in the neoplastic duct cell compartment of mixed neoplasms. Third, the proliferation/apoptosis ratio in cells from all lesion types remains constant, suggesting that differential regulation of these processes is not a feature of cancer progression in this model. Fourth, before the development of mixed neoplasms, there is transcriptional activation of the duct cell-specific cytokeratin-19 gene promoter in multicellular foci of amylase-positive acinar neoplasms. This observation provides direct evidence for metaplasia as the mechanism underlying development of ductal neoplastic cells within the context of an acinar neoplasm and suggests that the stimulus for this transformation acts over a multicellular domain or field within a neoplasm. Finally, focal ductal elements develop in some acinar cell carcinomas in Ela-c-myc transgenic rats, indicating that myc-associated acinar-to-ductal metaplasia is not restricted to the mouse.}, } @article {pmid22022374, year = {2011}, author = {Chouhan, B and Denesyuk, A and Heino, J and Johnson, MS and Denessiouk, K}, title = {Conservation of the human integrin-type beta-propeller domain in bacteria.}, journal = {PloS one}, volume = {6}, number = {10}, pages = {e25069}, pmid = {22022374}, issn = {1932-6203}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Bacteria/*metabolism ; Calcium/metabolism ; Consensus Sequence ; Conserved Sequence/*genetics ; Databases, Protein ; Humans ; Integrin alpha Chains/*chemistry ; Models, Molecular ; Molecular Sequence Data ; Protein Structure, Tertiary ; Repetitive Sequences, Amino Acid ; Sequence Alignment ; }, abstract = {Integrins are heterodimeric cell-surface receptors with key functions in cell-cell and cell-matrix adhesion. Integrin α and β subunits are present throughout the metazoans, but it is unclear whether the subunits predate the origin of multicellular organisms. Several component domains have been detected in bacteria, one of which, a specific 7-bladed β-propeller domain, is a unique feature of the integrin α subunits. Here, we describe a structure-derived motif, which incorporates key features of each blade from the X-ray structures of human αIIbβ3 and αVβ3, includes elements of the FG-GAP/Cage and Ca(2+)-binding motifs, and is specific only for the metazoan integrin domains. Separately, we searched for the metazoan integrin type β-propeller domains among all available sequences from bacteria and unicellular eukaryotic organisms, which must incorporate seven repeats, corresponding to the seven blades of the β-propeller domain, and so that the newly found structure-derived motif would exist in every repeat. As the result, among 47 available genomes of unicellular eukaryotes we could not find a single instance of seven repeats with the motif. Several sequences contained three repeats, a predicted transmembrane segment, and a short cytoplasmic motif associated with some integrins, but otherwise differ from the metazoan integrin α subunits. Among the available bacterial sequences, we found five examples containing seven sequential metazoan integrin-specific motifs within the seven repeats. The motifs differ in having one Ca(2+)-binding site per repeat, whereas metazoan integrins have three or four sites. The bacterial sequences are more conserved in terms of motif conservation and loop length, suggesting that the structure is more regular and compact than those example structures from human integrins. Although the bacterial examples are not full-length integrins, the full-length metazoan-type 7-bladed β-propeller domains are present, and sometimes two tandem copies are found.}, } @article {pmid22022256, year = {2011}, author = {Diekmann, Y and Seixas, E and Gouw, M and Tavares-Cadete, F and Seabra, MC and Pereira-Leal, JB}, title = {Thousands of rab GTPases for the cell biologist.}, journal = {PLoS computational biology}, volume = {7}, number = {10}, pages = {e1002217}, pmid = {22022256}, issn = {1553-7358}, mesh = {Animals ; Databases, Protein ; Humans ; Phylogeny ; Protein Transport ; rab GTP-Binding Proteins/classification/*metabolism ; }, abstract = {Rab proteins are small GTPases that act as essential regulators of vesicular trafficking. 44 subfamilies are known in humans, performing specific sets of functions at distinct subcellular localisations and tissues. Rab function is conserved even amongst distant orthologs. Hence, the annotation of Rabs yields functional predictions about the cell biology of trafficking. So far, annotating Rabs has been a laborious manual task not feasible for current and future genomic output of deep sequencing technologies. We developed, validated and benchmarked the Rabifier, an automated bioinformatic pipeline for the identification and classification of Rabs, which achieves up to 90% classification accuracy. We cataloged roughly 8.000 Rabs from 247 genomes covering the entire eukaryotic tree. The full Rab database and a web tool implementing the pipeline are publicly available at www.RabDB.org. For the first time, we describe and analyse the evolution of Rabs in a dataset covering the whole eukaryotic phylogeny. We found a highly dynamic family undergoing frequent taxon-specific expansions and losses. We dated the origin of human subfamilies using phylogenetic profiling, which enlarged the Rab repertoire of the Last Eukaryotic Common Ancestor with Rab14, 32 and RabL4. Furthermore, a detailed analysis of the Choanoflagellate Monosiga brevicollis Rab family pinpointed the changes that accompanied the emergence of Metazoan multicellularity, mainly an important expansion and specialisation of the secretory pathway. Lastly, we experimentally establish tissue specificity in expression of mouse Rabs and show that neo-functionalisation best explains the emergence of new human Rab subfamilies. With the Rabifier and RabDB, we provide tools that easily allows non-bioinformaticians to integrate thousands of Rabs in their analyses. RabDB is designed to enable the cell biology community to keep pace with the increasing number of fully-sequenced genomes and change the scale at which we perform comparative analysis in cell biology.}, } @article {pmid22012863, year = {2012}, author = {Ramachandran, S and Palanisamy, V}, title = {Horizontal transfer of RNAs: exosomes as mediators of intercellular communication.}, journal = {Wiley interdisciplinary reviews. RNA}, volume = {3}, number = {2}, pages = {286-293}, pmid = {22012863}, issn = {1757-7012}, support = {R00 DE018165-05/DE/NIDCR NIH HHS/United States ; R00 DE018165/DE/NIDCR NIH HHS/United States ; P20RR017696/RR/NCRR NIH HHS/United States ; R00DE018165/DE/NIDCR NIH HHS/United States ; P20 RR017696/RR/NCRR NIH HHS/United States ; }, mesh = {*Cell Communication ; Cell Membrane/metabolism ; Exosomes/*metabolism ; RNA/*metabolism ; Signal Transduction ; }, abstract = {Multicellular organisms are similar to biological communities, consisting of various cell types; thus, inter-cell communication is critical for the functioning of the whole system that ultimately constitutes a living being. Conventional models of cellular exchange include signaling molecules and direct contact-mediated cell communications. Exosomes, small vesicles originating from an inward budding of the plasma membrane, represent a new avenue for signaling between cells. This interchange is achieved by packaging RNA species into exosomes endowed with specific cell surface-targeting motifs. The delivered RNA molecules are functional, and mRNA can be translated into new proteins, while microRNAs (miRNAs) target host mRNAs in the recipient cell. RNA involved in transmitting information or molecules between cells is called exosomal RNA (esRNA). This review summarizes the characteristics of exosomes, specifically focusing on their role in the horizontal transfer of cellular information.}, } @article {pmid22001400, year = {2012}, author = {Potolicchio, I and Cigliola, V and Velazquez-Garcia, S and Klee, P and Valjevac, A and Kapic, D and Cosovic, E and Lepara, O and Hadzovic-Dzuvo, A and Mornjacovic, Z and Meda, P}, title = {Connexin-dependent signaling in neuro-hormonal systems.}, journal = {Biochimica et biophysica acta}, volume = {1818}, number = {8}, pages = {1919-1936}, doi = {10.1016/j.bbamem.2011.09.022}, pmid = {22001400}, issn = {0006-3002}, mesh = {Animals ; Connexins/*physiology ; Dopamine/metabolism ; Endocrine System/physiology ; Female ; Gonadotropin-Releasing Hormone/metabolism ; Hormones/*metabolism ; Humans ; Insulin/metabolism ; Kidney Cortex/metabolism ; Male ; Models, Biological ; Neurons/*metabolism ; Oxytocin/metabolism ; Renin/metabolism ; Signal Transduction ; Vasopressins/metabolism ; }, abstract = {The advent of multicellular organisms was accompanied by the development of short- and long-range chemical signalling systems, including those provided by the nervous and endocrine systems. In turn, the cells of these two systems have developed mechanisms for interacting with both adjacent and distant cells. With evolution, such mechanisms have diversified to become integrated in a complex regulatory network, whereby individual endocrine and neuro-endocrine cells sense the state of activity of their neighbors and, accordingly, regulate their own level of functioning. A consistent feature of this network is the expression of connexin-made channels between the (neuro)hormone-producing cells of all endocrine glands and secretory regions of the central nervous system so far investigated in vertebrates. This review summarizes the distribution of connexins in the mammalian (neuro)endocrine systems, and what we know about the participation of these proteins on hormone secretion, the life of the producing cells, and the action of (neuro)hormones on specific targets. The data gathered since the last reviews on the topic are summarized, with particular emphasis on the roles of Cx36 in the function of the insulin-producing beta cells of the endocrine pancreas, and of Cx40 in that of the renin-producing juxta-glomerular epithelioid cells of the kidney cortex. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.}, } @article {pmid22000039, year = {2012}, author = {Jönsson, H and Gruel, J and Krupinski, P and Troein, C}, title = {On evaluating models in Computational Morphodynamics.}, journal = {Current opinion in plant biology}, volume = {15}, number = {1}, pages = {103-110}, doi = {10.1016/j.pbi.2011.09.007}, pmid = {22000039}, issn = {1879-0356}, mesh = {*Models, Biological ; *Morphogenesis ; Plant Development ; Plant Growth Regulators/metabolism ; Plants/metabolism ; Stem Cells/cytology/metabolism ; }, abstract = {Recent advances in experimental plant biology have led to an increased potential to investigate plant development at a systems level. The emerging research field of Computational Morphodynamics has the aim to lead this development by combining dynamic spatial experimental data with computational models of molecular networks, growth, and mechanics in a multicellular context. The increased number of published models may lead to a diversification of our understanding of the systems, and methods for evaluating, comparing, and sharing models are main challenges for the future. We will discuss this problem using ideas originating from physics and use recent computational models of plant development as examples.}, } @article {pmid21998598, year = {2011}, author = {Debat, V and Bloyer, S and Faradji, F and Gidaszewski, N and Navarro, N and Orozco-Terwengel, P and Ribeiro, V and Schlötterer, C and Deutsch, JS and Peronnet, F}, title = {Developmental stability: a major role for cyclin G in drosophila melanogaster.}, journal = {PLoS genetics}, volume = {7}, number = {10}, pages = {e1002314}, pmid = {21998598}, issn = {1553-7404}, mesh = {Animals ; Base Sequence ; Body Patterning/genetics ; Cyclin G/genetics/*physiology ; Drosophila Proteins/genetics/*physiology ; Drosophila melanogaster/genetics/*growth & development ; Gene Regulatory Networks ; Genetic Variation ; Genotype ; Molecular Sequence Data ; Phenotype ; RNA Interference ; Wings, Animal/anatomy & histology/*growth & development ; }, abstract = {Morphological consistency in metazoans is remarkable given the pervasive occurrence of genetic variation, environmental effects, and developmental noise. Developmental stability, the ability to reduce developmental noise, is a fundamental property of multicellular organisms, yet its genetic bases remains elusive. Imperfect bilateral symmetry, or fluctuating asymmetry, is commonly used to estimate developmental stability. We observed that Drosophila melanogaster overexpressing Cyclin G (CycG) exhibit wing asymmetry clearly detectable by sight. Quantification of wing size and shape using geometric morphometrics reveals that this asymmetry is a genuine-but extreme-fluctuating asymmetry. Overexpression of CycG indeed leads to a 40-fold increase of wing fluctuating asymmetry, which is an unprecedented effect, for any organ and in any animal model, either in wild populations or mutants. This asymmetry effect is not restricted to wings, since femur length is affected as well. Inactivating CycG by RNAi also induces fluctuating asymmetry but to a lesser extent. Investigating the cellular bases of the phenotypic effects of CycG deregulation, we found that misregulation of cell size is predominant in asymmetric flies. In particular, the tight negative correlation between cell size and cell number observed in wild-type flies is impaired when CycG is upregulated. Our results highlight the role of CycG in the control of developmental stability in D. melanogaster. Furthermore, they show that wing developmental stability is normally ensured via compensatory processes between cell growth and cell proliferation. We discuss the possible role of CycG as a hub in a genetic network that controls developmental stability.}, } @article {pmid21998573, year = {2011}, author = {Ten Tusscher, KH and Hogeweg, P}, title = {Evolution of networks for body plan patterning; interplay of modularity, robustness and evolvability.}, journal = {PLoS computational biology}, volume = {7}, number = {10}, pages = {e1002208}, pmid = {21998573}, issn = {1553-7358}, mesh = {Animals ; *Biological Evolution ; Body Patterning/*genetics ; Computational Biology ; Computer Simulation ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; *Models, Genetic ; }, abstract = {A major goal of evolutionary developmental biology (evo-devo) is to understand how multicellular body plans of increasing complexity have evolved, and how the corresponding developmental programs are genetically encoded. It has been repeatedly argued that key to the evolution of increased body plan complexity is the modularity of the underlying developmental gene regulatory networks (GRNs). This modularity is considered essential for network robustness and evolvability. In our opinion, these ideas, appealing as they may sound, have not been sufficiently tested. Here we use computer simulations to study the evolution of GRNs' underlying body plan patterning. We select for body plan segmentation and differentiation, as these are considered to be major innovations in metazoan evolution. To allow modular networks to evolve, we independently select for segmentation and differentiation. We study both the occurrence and relation of robustness, evolvability and modularity of evolved networks. Interestingly, we observed two distinct evolutionary strategies to evolve a segmented, differentiated body plan. In the first strategy, first segments and then differentiation domains evolve (SF strategy). In the second scenario segments and domains evolve simultaneously (SS strategy). We demonstrate that under indirect selection for robustness the SF strategy becomes dominant. In addition, as a byproduct of this larger robustness, the SF strategy is also more evolvable. Finally, using a combined functional and architectural approach, we determine network modularity. We find that while SS networks generate segments and domains in an integrated manner, SF networks use largely independent modules to produce segments and domains. Surprisingly, we find that widely used, purely architectural methods for determining network modularity completely fail to establish this higher modularity of SF networks. Finally, we observe that, as a free side effect of evolving segmentation and differentiation in combination, we obtained in-silico developmental mechanisms resembling mechanisms used in vertebrate development.}, } @article {pmid21988647, year = {2012}, author = {Wang, XD and Song, Y and Sheahan, MB and Garg, ML and Rose, RJ}, title = {From embryo sac to oil and protein bodies: embryo development in the model legume Medicago truncatula.}, journal = {The New phytologist}, volume = {193}, number = {2}, pages = {327-338}, doi = {10.1111/j.1469-8137.2011.03925.x}, pmid = {21988647}, issn = {1469-8137}, mesh = {Cotyledon/cytology/ultrastructure ; Fatty Acids/biosynthesis ; Fertilization ; Flowers/cytology/ultrastructure ; Gene Expression Regulation, Plant ; Medicago truncatula/cytology/*embryology/genetics/ultrastructure ; Microscopy, Fluorescence ; *Models, Biological ; Organ Specificity/genetics ; Phylogeny ; Plant Oils/*metabolism ; Plant Proteins/genetics/*metabolism ; Seed Storage Proteins/genetics/metabolism ; Seeds/cytology/*metabolism/ultrastructure ; Zygote/cytology/ultrastructure ; }, abstract = {• The cell and developmental biology of zygotic embryogenesis in the model legume Medicago truncatula has received little attention. We studied M. truncatula embryogenesis from embryo sac until cotyledon maturation, including oil and protein body biogenesis. • We characterized embryo development using light and electron microscopy, measurement of protein and lipid fatty acid accumulation and by profiling the expression of key seed storage genes. • Embryo sac development in M. truncatula is of the Polygonum type. A distinctive multicellular hypophysis and suspensor develops before the globular stage and by the early cotyledon stage, the procambium connects the developing apical meristems. In the storage parenchyma of cotyledons, ovoid oil bodies surround protein bodies and the plasma membrane. Four major lipid fatty acids accumulate as cotyledons develop, paralleling the expression of OLEOSIN and the storage protein genes, VICILIN and LEGUMIN. • Zygotic embryogenesis in M. truncatula features the development of a distinctive multicellular hypophysis and an endopolyploid suspensor with basal transfer cell. A clear procambial connection between the apical meristems is evident and there is a characteristic arrangement of oil bodies in the cotyledons and radicle. Our data help link embryogenesis to the genetic regulation of oil and protein body biogenesis in legume seed.}, } @article {pmid21983084, year = {2011}, author = {Casas-Delucchi, CS and Cardoso, MC}, title = {Epigenetic control of DNA replication dynamics in mammals.}, journal = {Nucleus (Austin, Tex.)}, volume = {2}, number = {5}, pages = {370-382}, doi = {10.4161/nucl.2.5.17861}, pmid = {21983084}, issn = {1949-1042}, mesh = {Animals ; Chromatin/metabolism ; DNA Methylation ; *DNA Replication ; *Epigenesis, Genetic ; Histones/metabolism ; Humans ; Replication Origin ; Replicon ; Saccharomyces cerevisiae/genetics/metabolism ; }, abstract = {Every time a cell divides it must ensure that its genetic information is accurately duplicated and dis-tributed equally to the two daughter cells. This fundamental biological process is conserved through-out all kingdoms of life and relies on the correct and complete duplication of the DNA before a cell can divide and give rise to other cells or to multicellular organisms. Any mistakes in this process can result in genetic mutations or karyotype aberrations, which may lead to disease or even death. Whereas in prokaryotes the entire genome is replicated from a single origin, the increased genome size and complexity in mammals requires the spatio-temporal coordination of thousands of replica-tion origins. Furthermore, this spatio-temporal order of genome replication changes throughout de-velopment and cellular differentiation. Here we present and discuss current knowledge on the con-trol of DNA replication dynamics in mammals and the role of chromatin modifications in this basic biological process.}, } @article {pmid21980417, year = {2011}, author = {Wang, D and Calla, B and Vimolmangkang, S and Wu, X and Korban, SS and Huber, SC and Clough, SJ and Zhao, Y}, title = {The orphan gene ybjN conveys pleiotropic effects on multicellular behavior and survival of Escherichia coli.}, journal = {PloS one}, volume = {6}, number = {9}, pages = {e25293}, pmid = {21980417}, issn = {1932-6203}, mesh = {Escherichia coli/*cytology/genetics/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; Gene Expression Regulation, Bacterial/genetics/physiology ; Mutation ; Temperature ; }, abstract = {YbjN, encoding an enterobacteria-specific protein, is a multicopy suppressor of temperature sensitivity in the ts9 mutant strain of Escherichia coli. In this study, we further explored the role(s) of ybjN. First, we demonstrated that the ybjN transcript was about 10-fold lower in the ts9 strain compared to that of E. coli strain BW25113 (BW). Introduction of multiple copies of ybjN in the ts9 strain resulted in over-expression of ybjN by about 10-fold as compared to that of BW. These results suggested that temperature sensitivity of the ts9 mutant of E. coli may be related to expression levels of ybjN. Characterization of E. coli ybjN mutant revealed that ybjN mutation resulted in pleiotropic phenotypes, including increased motility, fimbriation (auto-aggregation), exopolysaccharide production, and biofilm formation. In contrast, over-expression of ybjN (in terms of multiple copies) resulted in reduced motility, fimbriation, exopolysaccharide production, biofilm formation and acid resistance. In addition, our results indicate that a ybjN-homolog gene from Erwinia amylovora, a plant enterobacterial pathogen, is functionally conserved with that of E. coli, suggesting similar evolution of the YbjN family proteins in enterobacteria. A microarray study revealed that the expression level of ybjN was inversely correlated with the expression of flagellar, fimbrial and acid resistance genes. Over-expression of ybjN significantly down-regulated genes involved in citric acid cycle, glycolysis, the glyoxylate shunt, oxidative phosphorylation, amino acid and nucleotide metabolism. Furthermore, over-expression of ybjN up-regulated toxin-antitoxin modules, the SOS response pathway, cold shock and starvation induced transporter genes. Collectively, these results suggest that YbjN may play important roles in regulating bacterial multicellular behavior, metabolism, and survival under stress conditions in E. coli. These results also suggest that ybjN over-expression-related temperature rescue of the ts9 mutant may be due to down-regulation of metabolic activity and activation of stress response genes in the ts9 mutant.}, } @article {pmid21980300, year = {2011}, author = {Jimenez-Gomez, JM and Corwin, JA and Joseph, B and Maloof, JN and Kliebenstein, DJ}, title = {Genomic analysis of QTLs and genes altering natural variation in stochastic noise.}, journal = {PLoS genetics}, volume = {7}, number = {9}, pages = {e1002295}, pmid = {21980300}, issn = {1553-7404}, mesh = {Arabidopsis/*genetics ; Arabidopsis Proteins/*genetics ; Biological Evolution ; Chromosome Mapping ; Crosses, Genetic ; Gene Expression Profiling/*statistics & numerical data ; Genomics/*statistics & numerical data ; Genotype ; Glucosinolates/*genetics ; Phenotype ; Polymorphism, Genetic ; Quantitative Trait Loci/*genetics ; Transcription Factors/*genetics ; }, abstract = {Quantitative genetic analysis has long been used to study how natural variation of genotype can influence an organism's phenotype. While most studies have focused on genetic determinants of phenotypic average, it is rapidly becoming understood that stochastic noise is genetically determined. However, it is not known how many traits display genetic control of stochastic noise nor how broadly these stochastic loci are distributed within the genome. Understanding these questions is critical to our understanding of quantitative traits and how they relate to the underlying causal loci, especially since stochastic noise may be directly influenced by underlying changes in the wiring of regulatory networks. We identified QTLs controlling natural variation in stochastic noise of glucosinolates, plant defense metabolites, as well as QTLs for stochastic noise of related transcripts. These loci included stochastic noise QTLs unique for either transcript or metabolite variation. Validation of these loci showed that genetic polymorphism within the regulatory network alters stochastic noise independent of effects on corresponding average levels. We examined this phenomenon more globally, using transcriptomic datasets, and found that the Arabidopsis transcriptome exhibits significant, heritable differences in stochastic noise. Further analysis allowed us to identify QTLs that control genomic stochastic noise. Some genomic QTL were in common with those altering average transcript abundance, while others were unique to stochastic noise. Using a single isogenic population, we confirmed that natural variation at ELF3 alters stochastic noise in the circadian clock and metabolism. Since polymorphisms controlling stochastic noise in genomic phenotypes exist within wild germplasm for naturally selected phenotypes, this suggests that analysis of Arabidopsis evolution should account for genetic control of stochastic variance and average phenotypes. It remains to be determined if natural genetic variation controlling stochasticity is equally distributed across the genomes of other multi-cellular eukaryotes.}, } @article {pmid21978297, year = {2012}, author = {Zhou, K and Zhang, WY and Yu-Zhang, K and Pan, HM and Zhang, SD and Zhang, WJ and Yue, HD and Li, Y and Xiao, T and Wu, LF}, title = {A novel genus of multicellular magnetotactic prokaryotes from the Yellow Sea.}, journal = {Environmental microbiology}, volume = {14}, number = {2}, pages = {405-413}, doi = {10.1111/j.1462-2920.2011.02590.x}, pmid = {21978297}, issn = {1462-2920}, mesh = {Base Sequence ; China ; Deltaproteobacteria/classification/genetics/*physiology/ultrastructure ; Magnetics ; Magnetosomes/metabolism ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Molecular Sequence Data ; Phylogeny ; Prokaryotic Cells ; }, abstract = {Multicellular magnetotactic prokaryotes (MMPs) are a group of magnetotactic microorganisms composed of 10-40 Gram-negative cells. Currently, all the identified MMPs show a spherical morphology and synthesize mainly iron sulfide magnetosomes. In this study, we report a novel genus of MMPs with peculiar ellipsoidal morphology and iron oxide magnetosomes, which were discovered in intertidal sediment of the Yellow Sea in China. Optical and fluorescence microscopy revealed that this organism was ~10 × 8 µm in size and composed of ~40 cells enveloped by an outer layer. Scanning electron microscopy showed that the cells were arranged in 4-6 interlaced circles. Bullet-shaped magnetite magnetosomes were organized in chains roughly parallel to the long axis of the ellipsoidal MMPs when analysed by transmission electron microscopy. These MMPs displayed special escape motility, i.e. swimming rapidly from the edge to the centre of the droplet and then slowly back to the edge. In addition, they exhibited negative phototaxis. Light microscopy observations showed that the ellipsoidal MMPs reproduced by division along the body long axis. Both analysis of 16S rRNA gene sequence and fluorescence in situ hybridization revealed the ellipsoidal MMPs as a new genus of the Deltaproteobacteria. In summary, this novel genus of MMPs exhibit unique morphology, peculiar division process and distinct phylogenetic affiliation compared with the other MMPs.}, } @article {pmid21966561, year = {2011}, author = {Schirrmeister, BE and Anisimova, M and Antonelli, A and Bagheri, HC}, title = {Evolution of cyanobacterial morphotypes: Taxa required for improved phylogenomic approaches.}, journal = {Communicative & integrative biology}, volume = {4}, number = {4}, pages = {424-427}, pmid = {21966561}, issn = {1942-0889}, abstract = {Within prokaryotes cyanobacteria represent one of the oldest and morphologically most diverse phyla on Earth. The rise of oxygen levels in the atmosphere 2.32-2.45 billion years ago is assigned to the photosynthetic activity of ancestors from this phylum. Subsequently cyanobacteria were able to adapt to various habitats evolving a comprehensive set of different morphotypes. In a recent study we showed that this evolution is not a gradual transition from simple unicellular to more complex multicellular forms as often assumed. Instead complexity was lost several times and regained at least once. An understanding of the genetic basis of these transitions would be further strengthened by phylogenomic approaches. However, considering that new methods for phylogenomic analyses are emerging, it is unfortunate that genomes available today are comprised of an unbalanced sampling of taxa. We propose avenues to remedy this by identifying taxa that would improve the representation of phylogenetic diversity in this phylum.}, } @article {pmid21965654, year = {2011}, author = {Olmedo-Verd, E and Santamaría-Gómez, J and Ochoa de Alda, JA and Ribas de Pouplana, L and Luque, I}, title = {Membrane anchoring of aminoacyl-tRNA synthetases by convergent acquisition of a novel protein domain.}, journal = {The Journal of biological chemistry}, volume = {286}, number = {47}, pages = {41057-41068}, pmid = {21965654}, issn = {1083-351X}, mesh = {Amino Acid Sequence ; Amino Acyl-tRNA Synthetases/*chemistry/genetics/*metabolism ; Anabaena/cytology/enzymology ; Cell Membrane/*enzymology/metabolism ; Evolution, Molecular ; Intracellular Space/metabolism ; Molecular Sequence Data ; Protein Structure, Tertiary ; Protein Transport ; Valine-tRNA Ligase/metabolism ; }, abstract = {Four distinct aminoacyl-tRNA synthetases (aaRSs) found in some cyanobacterial species contain a novel protein domain that bears two putative transmembrane helices. This CAAD domain is present in glutamyl-, isoleucyl-, leucyl-, and valyl-tRNA synthetases, the latter of which has probably recruited the domain more than once during evolution. Deleting the CAAD domain from the valyl-tRNA synthetase of Anabaena sp. PCC 7120 did not significantly modify the catalytic properties of this enzyme, suggesting that it does not participate in its canonical tRNA-charging function. Multiple lines of evidence suggest that the function of the CAAD domain is structural, mediating the membrane anchorage of the enzyme, although membrane localization of aaRSs has not previously been described in any living organism. Synthetases containing the CAAD domain were localized in the intracytoplasmic thylakoid membranes of cyanobacteria and were largely absent from the plasma membrane. The CAAD domain was necessary and apparently sufficient for protein targeting to membranes. Moreover, localization of aaRSs in thylakoids was important under nitrogen limiting conditions. In Anabaena, a multicellular filamentous cyanobacterium often used as a model for prokaryotic cell differentiation, valyl-tRNA synthetase underwent subcellular relocation at the cell poles during heterocyst differentiation, a process also dependent on the CAAD domain.}, } @article {pmid21949685, year = {2011}, author = {Chlenski, A and Guerrero, LJ and Salwen, HR and Yang, Q and Tian, Y and Morales La Madrid, A and Mirzoeva, S and Bouyer, PG and Xu, D and Walker, M and Cohn, SL}, title = {Secreted protein acidic and rich in cysteine is a matrix scavenger chaperone.}, journal = {PloS one}, volume = {6}, number = {9}, pages = {e23880}, pmid = {21949685}, issn = {1932-6203}, mesh = {Animals ; Calcium/metabolism ; Cells, Cultured ; Collagen/metabolism/pharmacokinetics ; Extracellular Matrix/*metabolism ; Extracellular Matrix Proteins/*metabolism ; Extracellular Space/metabolism ; Female ; Fibroblasts/cytology/metabolism ; HEK293 Cells ; Humans ; Intracellular Space/metabolism ; Male ; Mice ; Mice, 129 Strain ; Mice, Knockout ; Microscopy, Fluorescence ; Molecular Chaperones/*metabolism ; NIH 3T3 Cells ; Osteonectin/genetics/*metabolism/pharmacokinetics ; Protein Transport ; }, abstract = {Secreted Protein Acidic and Rich in Cysteine (SPARC) is one of the major non-structural proteins of the extracellular matrix (ECM) in remodeling tissues. The functional significance of SPARC is emphasized by its origin in the first multicellular organisms and its high degree of evolutionary conservation. Although SPARC has been shown to act as a critical modulator of ECM remodeling with profound effects on tissue physiology and architecture, no plausible molecular mechanism of its action has been proposed. In the present study, we demonstrate that SPARC mediates the disassembly and degradation of ECM networks by functioning as a matricellular chaperone. While it has low affinity to its targets inside the cells where the Ca(2+) concentrations are low, high extracellular concentrations of Ca(2+) activate binding to multiple ECM proteins, including collagens. We demonstrated that in vitro, this leads to the inhibition of collagen I fibrillogenesis and disassembly of pre-formed collagen I fibrils by SPARC at high Ca(2+) concentrations. In cell culture, exogenous SPARC was internalized by the fibroblast cells in a time- and concentration-dependent manner. Pulse-chase assay further revealed that internalized SPARC is quickly released outside the cell, demonstrating that SPARC shuttles between the cell and ECM. Fluorescently labeled collagen I, fibronectin, vitronectin, and laminin were co-internalized with SPARC by fibroblasts, and semi-quantitative Western blot showed that SPARC mediates internalization of collagen I. Using a novel 3-dimensional model of fluorescent ECM networks pre-deposited by live fibroblasts, we demonstrated that degradation of ECM depends on the chaperone activity of SPARC. These results indicate that SPARC may represent a new class of scavenger chaperones, which mediate ECM degradation, remodeling and repair by disassembling ECM networks and shuttling ECM proteins into the cell. Further understanding of this mechanism may provide insight into the pathogenesis of matrix-associated disorders and lead to the novel treatment strategies.}, } @article {pmid21949639, year = {2011}, author = {Schmidt, A and Wuest, SE and Vijverberg, K and Baroux, C and Kleen, D and Grossniklaus, U}, title = {Transcriptome analysis of the Arabidopsis megaspore mother cell uncovers the importance of RNA helicases for plant germline development.}, journal = {PLoS biology}, volume = {9}, number = {9}, pages = {e1001155}, pmid = {21949639}, issn = {1545-7885}, mesh = {*Arabidopsis/genetics/growth & development/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Cell Differentiation/genetics ; DNA, Bacterial/chemistry/genetics ; Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; *Genome, Plant ; Germ Cells, Plant/cytology/*metabolism ; In Situ Hybridization ; Meiosis ; Microdissection ; Mutagenesis, Insertional ; Oligonucleotide Array Sequence Analysis ; Ovule/*genetics/metabolism ; Phylogeny ; Protein Biosynthesis ; *RNA Helicases/genetics/metabolism ; Stem Cells/cytology/*metabolism ; Transcriptome/*genetics ; }, abstract = {Germ line specification is a crucial step in the life cycle of all organisms. For sexual plant reproduction, the megaspore mother cell (MMC) is of crucial importance: it marks the first cell of the plant "germline" lineage that gets committed to undergo meiosis. One of the meiotic products, the functional megaspore, subsequently gives rise to the haploid, multicellular female gametophyte that harbours the female gametes. The MMC is formed by selection and differentiation of a single somatic, sub-epidermal cell in the ovule. The transcriptional network underlying MMC specification and differentiation is largely unknown. We provide the first transcriptome analysis of an MMC using the model plant Arabidopsis thaliana with a combination of laser-assisted microdissection and microarray hybridizations. Statistical analyses identified an over-representation of translational regulation control pathways and a significant enrichment of DEAD/DEAH-box helicases in the MMC transcriptome, paralleling important features of the animal germline. Analysis of two independent T-DNA insertion lines suggests an important role of an enriched helicase, MNEME (MEM), in MMC differentiation and the restriction of the germline fate to only one cell per ovule primordium. In heterozygous mem mutants, additional enlarged MMC-like cells, which sometimes initiate female gametophyte development, were observed at higher frequencies than in the wild type. This closely resembles the phenotype of mutants affected in the small RNA and DNA-methylation pathways important for epigenetic regulation. Importantly, the mem phenotype shows features of apospory, as female gametophytes initiate from two non-sister cells in these mutants. Moreover, in mem gametophytic nuclei, both higher order chromatin structure and the distribution of LIKE HETEROCHROMATIN PROTEIN1 were affected, indicating epigenetic perturbations. In summary, the MMC transcriptome sets the stage for future functional characterization as illustrated by the identification of MEM, a novel gene involved in the restriction of germline fate.}, } @article {pmid21945788, year = {2011}, author = {Rehm, P and Borner, J and Meusemann, K and von Reumont, BM and Simon, S and Hadrys, H and Misof, B and Burmester, T}, title = {Dating the arthropod tree based on large-scale transcriptome data.}, journal = {Molecular phylogenetics and evolution}, volume = {61}, number = {3}, pages = {880-887}, doi = {10.1016/j.ympev.2011.09.003}, pmid = {21945788}, issn = {1095-9513}, mesh = {Animals ; Arthropods/*genetics ; Bayes Theorem ; Calibration ; Evolution, Molecular ; Genetic Variation ; Models, Genetic ; *Phylogeny ; Time Factors ; Transcriptome/*genetics ; }, abstract = {Molecular sequences do not only allow the reconstruction of phylogenetic relationships among species, but also provide information on the approximate divergence times. Whereas the fossil record dates the origin of most multicellular animal phyla during the Cambrian explosion less than 540 million years ago(mya), molecular clock calculations usually suggest much older dates. Here we used a large multiple sequence alignment derived from Expressed Sequence Tags and genomes comprising 129genes (37,476 amino acid positions) and 117 taxa, including 101 arthropods. We obtained consistent divergence time estimates applying relaxed Bayesian clock models with different priors and multiple calibration points. While the influence of substitution rates, missing data, and model priors were negligible, the clock model had significant effect. A log-normal autocorrelated model was selected on basis of cross-validation. We calculated that arthropods emerged ~600 mya. Onychophorans (velvet worms) and euarthropods split ~590 mya, Pancrustacea and Myriochelata ~560 mya, Myriapoda and Chelicerata ~555 mya, and 'Crustacea' and Hexapoda ~510 mya. Endopterygote insects appeared ~390 mya. These dates are considerably younger than most previous molecular clock estimates and in better agreement with the fossil record. Nevertheless, a Precambrian origin of arthropods and other metazoan phyla is still supported. Our results also demonstrate the applicability of large datasets of random nuclear sequences for approximating the timing of multicellular animal evolution.}, } @article {pmid21937732, year = {2012}, author = {Hynes, RO and Naba, A}, title = {Overview of the matrisome--an inventory of extracellular matrix constituents and functions.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {4}, number = {1}, pages = {a004903}, pmid = {21937732}, issn = {1943-0264}, support = {P30 CA014051/CA/NCI NIH HHS/United States ; U54 CA163109/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Collagen/analysis/chemistry ; Evolution, Molecular ; Extracellular Matrix Proteins/*chemistry/*physiology ; Glycoproteins/analysis/chemistry ; Humans ; Integrins/physiology ; Proteoglycans/analysis/chemistry ; Transforming Growth Factor beta/physiology ; }, abstract = {Completion of genome sequences for many organisms allows a reasonably complete definition of the complement of extracellular matrix (ECM) proteins. In mammals this "core matrisome" comprises ∼300 proteins. In addition there are large numbers of ECM-modifying enzymes, ECM-binding growth factors, and other ECM-associated proteins. These different categories of ECM and ECM-associated proteins cooperate to assemble and remodel extracellular matrices and bind to cells through ECM receptors. Together with receptors for ECM-bound growth factors, they provide multiple inputs into cells to control survival, proliferation, differentiation, shape, polarity, and motility of cells. The evolution of ECM proteins was key in the transition to multicellularity, the arrangement of cells into tissue layers, and the elaboration of novel structures during vertebrate evolution. This key role of ECM is reflected in the diversity of ECM proteins and the modular domain structures of ECM proteins both allow their multiple interactions and, during evolution, development of novel protein architectures.}, } @article {pmid21933443, year = {2011}, author = {Slade, KM and Freggiaro, S and Cottrell, KA and Smith, JJ and Wiley, EA}, title = {Sirtuin-mediated nuclear differentiation and programmed degradation in Tetrahymena.}, journal = {BMC cell biology}, volume = {12}, number = {}, pages = {40}, pmid = {21933443}, issn = {1471-2121}, mesh = {Active Transport, Cell Nucleus/drug effects ; Amino Acid Sequence ; Apoptosis/drug effects ; Cell Nucleus/*metabolism ; Cells, Cultured ; Chromatin Assembly and Disassembly/drug effects ; Conjugation, Genetic/drug effects ; DNA Fragmentation ; Meiosis/drug effects ; Mitochondria/*metabolism ; Molecular Sequence Data ; Niacinamide/pharmacology ; Phylogeny ; Protein Multimerization/drug effects ; Protein Transport ; Protozoan Proteins/antagonists & inhibitors/genetics/*metabolism ; Sirtuins/antagonists & inhibitors/genetics/*metabolism ; Tetrahymena/*physiology ; }, abstract = {BACKGROUND: The NAD(+)-dependent histone deacetylases, known as "sirtuins", participate in a variety of processes critical for single- and multi-cellular life. Recent studies have elucidated the importance of sirtuin activity in development, aging, and disease; yet, underlying mechanistic pathways are not well understood. Specific sirtuins influence chromatin structure and gene expression, but differences in their pathways as they relate to distinct chromatin functions are just beginning to emerge. To further define the range of global chromatin changes dependent on sirtuins, unique biological features of the ciliated protozoan Tetrahymena thermophila can be exploited. This system offers clear spatial and temporal separation of multiple whole genome restructuring events critical for the life cycle.

RESULTS: Inhibition with nicotinamide revealed that sirtuin deacetylase activity in Tetrahymena cells promotes chromatin condensation during meiotic prophase, differentiation of heterochromatin from euchromatin during development, and chromatin condensation/degradation during programmed nuclear death. We identified a class I sirtuin, called Thd14, that resides in mitochondria and nucleoli during vegetative growth, and forms a large sub-nuclear aggregate in response to prolonged cell starvation that may be peripherally associated with nucleoli. During sexual conjugation and development Thd14 selectively concentrates in the parental nucleus prior to its apoptotic-like degradation.

CONCLUSIONS: Sirtuin activity is important for several functionally distinct events requiring global chromatin condensation. Our findings suggest a novel role for sirtuins in promoting programmed pycnosis by acting on chromatin destined for degradation. The sirtuin Thd14, which displays physiological-dependent differential localization within the nucleus, is a candidate for a chromatin condensation enzyme that is coupled to nuclear degradation.}, } @article {pmid21933388, year = {2011}, author = {Bron, JE and Frisch, D and Goetze, E and Johnson, SC and Lee, CE and Wyngaard, GA}, title = {Observing copepods through a genomic lens.}, journal = {Frontiers in zoology}, volume = {8}, number = {1}, pages = {22}, pmid = {21933388}, issn = {1742-9994}, abstract = {BACKGROUND: Copepods outnumber every other multicellular animal group. They are critical components of the world's freshwater and marine ecosystems, sensitive indicators of local and global climate change, key ecosystem service providers, parasites and predators of economically important aquatic animals and potential vectors of waterborne disease. Copepods sustain the world fisheries that nourish and support human populations. Although genomic tools have transformed many areas of biological and biomedical research, their power to elucidate aspects of the biology, behavior and ecology of copepods has only recently begun to be exploited.

DISCUSSION: The extraordinary biological and ecological diversity of the subclass Copepoda provides both unique advantages for addressing key problems in aquatic systems and formidable challenges for developing a focused genomics strategy. This article provides an overview of genomic studies of copepods and discusses strategies for using genomics tools to address key questions at levels extending from individuals to ecosystems. Genomics can, for instance, help to decipher patterns of genome evolution such as those that occur during transitions from free living to symbiotic and parasitic lifestyles and can assist in the identification of genetic mechanisms and accompanying physiological changes associated with adaptation to new or physiologically challenging environments. The adaptive significance of the diversity in genome size and unique mechanisms of genome reorganization during development could similarly be explored. Genome-wide and EST studies of parasitic copepods of salmon and large EST studies of selected free-living copepods have demonstrated the potential utility of modern genomics approaches for the study of copepods and have generated resources such as EST libraries, shotgun genome sequences, BAC libraries, genome maps and inbred lines that will be invaluable in assisting further efforts to provide genomics tools for copepods.

SUMMARY: Genomics research on copepods is needed to extend our exploration and characterization of their fundamental biological traits, so that we can better understand how copepods function and interact in diverse environments. Availability of large scale genomics resources will also open doors to a wide range of systems biology type studies that view the organism as the fundamental system in which to address key questions in ecology and evolution.}, } @article {pmid21927886, year = {2012}, author = {Rocha, DI and Vieira, LM and Tanaka, FA and da Silva, LC and Otoni, WC}, title = {Somatic embryogenesis of a wild passion fruit species Passiflora cincinnata Masters: histocytological and histochemical evidences.}, journal = {Protoplasma}, volume = {249}, number = {3}, pages = {747-758}, pmid = {21927886}, issn = {1615-6102}, mesh = {Cell Differentiation ; Cotyledon/cytology ; Passiflora/*cytology/physiology ; *Plant Somatic Embryogenesis Techniques ; Surface Properties ; }, abstract = {The characterization of cellular changes that occur during somatic embryogenesis is essential for understanding the factors involved in the transition of somatic cells into embryogenically competent cells and determination of cells and/or tissues involved. The present study describes the anatomical and ultrastructural events that lead to the formation of somatic embryos in the model system of the wild passion fruit (Passiflora cincinnata). Mature zygotic embryos were inoculated in Murashige and Skoog induction media supplemented with 2,4-dichlorophenoxyacetic acid and 6-benzyladenine. Zygotic embryo explants at different development stages were collected and processed by conventional methods for studies using light, scanning, and transmission electron microscopy (TEM). Histochemical tests were used to examine the mobilization of reserves. The differentiation of the somatic embryos began in the abaxial side of the cotyledon region. Protuberances were formed from the meristematic proliferation of the epidermal and mesophyll cells. These cells had large nuclei, dense cytoplasm with a predominance of mitochondria, and a few reserve compounds. The protuberances extended throughout the abaxial surface of the cotyledons. The ongoing differentiation of peripheral cells of these structures led to the formation of proembryogenic zones, which, in turn, dedifferentiated into somatic embryos of multicellular origin. In the initial stages of embryogenesis, the epidermal and mesophyll cells showed starch grains and less lipids and protein reserves than the starting explant. These results provide detailed information on anatomical and ultrastructural changes involved in the acquisition of embryogenic competence and embryo differentiation that has been lacking so far in Passiflora.}, } @article {pmid21912663, year = {2011}, author = {Wang, Q and Huang, J and Zhang, X and Wu, B and Liu, X and Shen, Z}, title = {The spatial association of gene expression evolves from synchrony to asynchrony and stochasticity with age.}, journal = {PloS one}, volume = {6}, number = {9}, pages = {e24076}, pmid = {21912663}, issn = {1932-6203}, mesh = {Aging/drug effects/*genetics ; Animals ; Caloric Restriction ; Female ; Male ; Mice ; Rats ; Resveratrol ; Stilbenes/pharmacology ; Stochastic Processes ; Time Factors ; Transcriptome/drug effects/*physiology ; }, abstract = {For multicellular organisms, different tissues coordinate to integrate physiological functions, although this systematically and gradually declines in the aging process. Therefore, an association exists between tissue coordination and aging, and investigating the evolution of tissue coordination with age is of interest. In the past decade, both common and heterogeneous aging processes among tissues were extensively investigated. The results on spatial association of gene changes that determine lifespan appear complex and paradoxical. To reconcile observed commonality and heterogeneity of gene changes among tissues and to address evolution feature of tissue coordination with age, we introduced a new analytical strategy to systematically analyze genome-wide spatio-temporal gene expression profiles. We first applied the approach to natural aging process in three species (Rat, Mouse and Drosophila) and then to anti-aging process in Mouse. The results demonstrated that temporal gene expression alteration in different tissues experiences a progressive association evolution from spatial synchrony to asynchrony and stochasticity with age. This implies that tissue coordination gradually declines with age. Male mice showed earlier spatial asynchrony in gene expression than females, suggesting that male animals are more prone to aging than females. The confirmed anti-aging interventions (resveratrol and caloric restriction) enhanced tissue coordination, indicating their underlying anti-aging mechanism on multiple tissue levels. Further, functional analysis suggested asynchronous DNA/protein damage accumulation as well as asynchronous repair, modification and degradation of DNA/protein in tissues possibly contributes to asynchronous and stochastic changes of tissue microenvironment. This increased risk for a variety of age-related diseases such as neurodegeneration and cancer that eventually accelerate organismal aging and death. Our study suggests a novel molecular event occurring in aging process of multicellular species that may represent an intrinsic molecular mechanism of aging.}, } @article {pmid21908106, year = {2011}, author = {Mori, N and Mori, M}, title = {Neuronal Shc: a gene of longevity in the brain?.}, journal = {Medical hypotheses}, volume = {77}, number = {6}, pages = {996-999}, doi = {10.1016/j.mehy.2011.08.030}, pmid = {21908106}, issn = {1532-2777}, mesh = {Animals ; *Biological Evolution ; Brain/*metabolism ; Brain-Derived Neurotrophic Factor/metabolism ; Humans ; *Longevity ; Mammals/genetics/*physiology ; N-Methylaspartate/metabolism ; Neurons/*metabolism ; Quality of Life ; Shc Signaling Adaptor Proteins/*metabolism ; Src Homology 2 Domain-Containing, Transforming Protein 1 ; Src Homology 2 Domain-Containing, Transforming Protein 3 ; }, abstract = {Aging is inevitable to all multi-cellular organisms, and each organism has its own lifespan. The species-specific lifespan seems determined genetically; however little is known about how the lifespan determined. During the last decades accumulative evidence indicates that there is certainly a set of genes that are involved in the lifespan determination. Among those dozens of genes, the Shc gene encoding a phosphotyrosine signal adaptor is of potential interests in mammalian aging and/or longevity determination. Shc is merely one form of a gene family, and accumulative evidence demonstrates the presence of additional Shc homologues that are strongly expressed in the nervous system. We hypothesize that lifespan is regulated primarily by the nervous system and/or brain, and neurally expressed Shc homologues play pivotal roles in relation to the evolution of longevity with quality of life. We discuss herein the recent progress of our understanding of the neuronally expressed Shc genes in comparision with p66-Shc as a candidate for the evolution of long life with higher quality of life in mammals.}, } @article {pmid21904874, year = {2012}, author = {Takahashi, N and Kami, C and Morita, N and Imaichi, R}, title = {Comparative development of heavily asymmetric-cordate gametophytes of Anemia phyllitidis (Anemiaceae) focusing on meristem behavior.}, journal = {Journal of plant research}, volume = {125}, number = {3}, pages = {371-380}, pmid = {21904874}, issn = {1618-0860}, mesh = {Cell Division ; Ferns/*cytology/*growth & development ; Germ Cells, Plant/*cytology/*growth & development ; Meristem/*cytology/*growth & development ; }, abstract = {Development of heavily asymmetric cordate gametophytes of Anemia phyllitidis (Anemiaceae), one of the schizaeoid ferns, was examined using a sequential observation technique; epi-illuminated light micrographs of the same growing gametophytes were taken approximately every 24 h. The apical cell-like wedge-shaped cell was produced once from the terminal cell of a germ filament, but it stopped dividing soon after production of one or two derivative cells. Without a functional apical cell, the gametophyte developed by intercalary growth until the early stage of wing formation, and then the multicellular (pluricellular) meristem arose from the lower lateral side of the gametophyte. This was in sharp contrast to the observation that the multicellular meristem forms in place of the apical cell in typical cordate gametophytes. Loss of the functional apical cell probably caused a site-shift in the multicellular meristem of the Anemia phyllitidis gametophyte during evolution from apical to lateral. The results suggest that apical cell-based and multicellular meristems are primarily independent of each other. The multicellular meristem produced cells equally in the distal and proximal directions to form wings in both directions but proximally produced cells divided much less frequently. As a result, a heavily asymmetric gametophyte was formed.}, } @article {pmid21899737, year = {2011}, author = {Yoshida, T and Claverie, JM and Ogata, H}, title = {Mimivirus reveals Mre11/Rad50 fusion proteins with a sporadic distribution in eukaryotes, bacteria, viruses and plasmids.}, journal = {Virology journal}, volume = {8}, number = {}, pages = {427}, pmid = {21899737}, issn = {1743-422X}, mesh = {Acid Anhydride Hydrolases ; Animals ; Aquatic Organisms/*genetics ; Archaeal Proteins/genetics ; Bacteria/genetics ; Bacterial Proteins/genetics ; Computational Biology ; DNA Breaks, Double-Stranded ; DNA Repair ; DNA Repair Enzymes/chemistry/*genetics ; DNA-Binding Proteins/chemistry/*genetics ; Databases, Genetic ; Deoxyribonucleases/genetics ; Endodeoxyribonucleases/chemistry/*genetics ; Escherichia coli Proteins/genetics ; Exodeoxyribonucleases/chemistry/*genetics ; Exonucleases/genetics ; Gene Transfer, Horizontal ; *Genome, Viral ; Humans ; *Metagenome ; Metagenomics ; Mimiviridae/chemistry/*genetics ; Phylogeny ; Plasmids/chemistry/genetics ; Saccharomyces cerevisiae Proteins/chemistry/*genetics ; Viral Fusion Proteins/chemistry/*genetics ; Viral Proteins/chemistry/*genetics ; }, abstract = {BACKGROUND: The Mre11/Rad50 complex and the homologous SbcD/SbcC complex in bacteria play crucial roles in the metabolism of DNA double-strand breaks, including DNA repair, genome replication, homologous recombination and non-homologous end-joining in cellular life forms and viruses. Here we investigated the amino acid sequence of the Mimivirus R555 gene product, originally annotated as a Rad50 homolog, and later shown to have close homologs in marine microbial metagenomes.

RESULTS: Our bioinformatics analysis revealed that R555 protein sequence is constituted from the fusion of an N-terminal Mre11-like domain with a C-terminal Rad50-like domain. A systematic database search revealed twelve additional cases of Mre11/Rad50 (or SbcD/SbcC) fusions in a wide variety of unrelated organisms including unicellular and multicellular eukaryotes, the megaplasmid of a bacterium associated to deep-sea hydrothermal vents (Deferribacter desulfuricans) and the plasmid of Clostridium kluyveri. We also showed that R555 homologs are abundant in the metagenomes from different aquatic environments and that they most likely belong to aquatic viruses. The observed phyletic distribution of these fusion proteins suggests their recurrent creation and lateral gene transfers across organisms.

CONCLUSIONS: The existence of the fused version of protein sequences is consistent with known functional interactions between Mre11 and Rad50, and the gene fusion probably enhanced the opportunity for lateral transfer. The abundance of the Mre11/Rad50 fusion genes in viral metagenomes and their sporadic phyletic distribution in cellular organisms suggest that viruses, plasmids and transposons played a crucial role in the formation of the fusion proteins and their propagation into cellular genomes.}, } @article {pmid21898828, year = {2012}, author = {Busch, A and Hertel, KJ}, title = {Evolution of SR protein and hnRNP splicing regulatory factors.}, journal = {Wiley interdisciplinary reviews. RNA}, volume = {3}, number = {1}, pages = {1-12}, pmid = {21898828}, issn = {1757-7012}, support = {R21 CA149548-02/CA/NCI NIH HHS/United States ; R01 GM62287/GM/NIGMS NIH HHS/United States ; R01 GM062287/GM/NIGMS NIH HHS/United States ; R01 GM062287-12/GM/NIGMS NIH HHS/United States ; R21 CA149548/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Nuclear Proteins/*genetics ; Phylogeny ; RNA Precursors/*genetics ; *RNA Splicing ; RNA-Binding Proteins/*genetics ; }, abstract = {The splicing of pre-mRNAs is an essential step of gene expression in eukaryotes. Introns are removed from split genes through the activities of the spliceosome, a large ribonuclear machine that is conserved throughout the eukaryotic lineage. While unicellular eukaryotes are characterized by less complex splicing, pre-mRNA splicing of multicellular organisms is often associated with extensive alternative splicing that significantly enriches their proteome. The alternative selection of splice sites and exons permits multicellular organisms to modulate gene expression patterns in a cell type-specific fashion, thus contributing to their functional diversification. Alternative splicing is a regulated process that is mainly influenced by the activities of splicing regulators, such as SR proteins or hnRNPs. These modular factors have evolved from a common ancestor through gene duplication events to a diverse group of splicing regulators that mediate exon recognition through their sequence-specific binding to pre-mRNAs. Given the strong correlations between intron expansion, the complexity of pre-mRNA splicing, and the emergence of splicing regulators, it is argued that the increased presence of SR and hnRNP proteins promoted the evolution of alternative splicing through relaxation of the sequence requirements of splice junctions.}, } @article {pmid21893873, year = {2011}, author = {Robu, A and Neagu, A and Stoicu-Tivadar, L}, title = {Cell seeding of tissue engineering scaffolds studied by Monte Carlo simulations.}, journal = {Studies in health technology and informatics}, volume = {169}, number = {}, pages = {882-886}, pmid = {21893873}, issn = {0926-9630}, mesh = {Algorithms ; Animals ; Biocompatible Materials/chemistry ; Cell Adhesion ; Cell Culture Techniques/*methods ; Cell Death ; Cell Proliferation ; Computational Biology/methods ; Computer Simulation ; Humans ; Models, Statistical ; Monte Carlo Method ; Tissue Engineering/*methods ; Tissue Scaffolds ; }, abstract = {Tissue engineering (TE) aims at building multicellular structures in the laboratory in order to regenerate, to repair or replace damaged tissues. In a well-established approach to TE, cells are cultured on a biocompatible porous structure, called scaffold. Cell seeding of scaffolds is an important first step. Here we study conditions that assure a uniform and rapid distribution of cells within the scaffold. The movement of cells has been simulated using the Metropolis Monte Carlo method, based on the principle that cellular system tends to achieve the minimum energy state. For different values of the model parameters, evolution of the cells' centre of mass is followed, which reflects the distribution of cells in the system. For comparison with experimental data, the concentration of the cells in the suspension adjacent to the scaffold is also monitored. Simulations of cell seeding are useful for testing different experimental conditions, which in practice would be very expensive and hard to perform. The computational methods presented here may be extended to model cell proliferation, cell death and scaffold degradation.}, } @article {pmid21889439, year = {2011}, author = {Efremov, A and Cao, J}, title = {Bistability of cell adhesion in shear flow.}, journal = {Biophysical journal}, volume = {101}, number = {5}, pages = {1032-1040}, pmid = {21889439}, issn = {1542-0086}, mesh = {Blood Vessels/cytology/metabolism ; *Cell Adhesion ; Cell Adhesion Molecules/metabolism ; Chemical Phenomena ; Leukocyte Rolling ; Leukocytes/cytology/metabolism ; *Models, Biological ; *Shear Strength ; }, abstract = {Cell adhesion plays a central role in multicellular organisms helping to maintain their integrity and homeostasis. This complex process involves many different types of adhesion proteins, and synergetic behavior of these proteins during cell adhesion is frequently observed in experiments. A well-known example is the cooperation of rolling and stationary adhesion proteins during the leukocytes extravasation. Despite the fact that such cooperation is vital for proper functioning of the immune system, its origin is not fully understood. In this study we constructed a simple analytic model of the interaction between a leukocyte and the blood vessel wall in shear flow. The model predicts existence of cell adhesion bistability, which results from a tug-of-war between two kinetic processes taking place in the cell-wall contact area-bond formation and rupture. Based on the model results, we suggest an interpretation of several cytoadhesion experiments and propose a simple explanation of the existing synergy between rolling and stationary adhesion proteins, which is vital for effective cell adherence to the blood vessel walls in living organisms.}, } @article {pmid21880160, year = {2011}, author = {Marshall, WF}, title = {Origins of cellular geometry.}, journal = {BMC biology}, volume = {9}, number = {}, pages = {57}, pmid = {21880160}, issn = {1741-7007}, support = {GM090305/GM/NIGMS NIH HHS/United States ; GM097017/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Biology ; Cell Polarity/physiology ; Cells/*cytology/metabolism ; Eukaryotic Cells/cytology/metabolism ; }, abstract = {Cells are highly complex and orderly machines, with defined shapes and a startling variety of internal organizations. Complex geometry is a feature of both free-living unicellular organisms and cells inside multicellular animals. Where does the geometry of a cell come from? Many of the same questions that arise in developmental biology can also be asked of cells, but in most cases we do not know the answers. How much of cellular organization is dictated by global cell polarity cues as opposed to local interactions between cellular components? Does cellular structure persist across cell generations? What is the relationship between cell geometry and tissue organization? What ensures that intracellular structures are scaled to the overall size of the cell? Cell biology is only now beginning to come to grips with these questions.}, } @article {pmid21867568, year = {2011}, author = {Shpilka, T and Weidberg, H and Pietrokovski, S and Elazar, Z}, title = {Atg8: an autophagy-related ubiquitin-like protein family.}, journal = {Genome biology}, volume = {12}, number = {7}, pages = {226}, pmid = {21867568}, issn = {1474-760X}, mesh = {Animals ; *Autophagy ; Evolution, Molecular ; Humans ; Protein Transport ; Ubiquitins/chemistry/*genetics/*physiology ; }, abstract = {Autophagy-related (Atg) proteins are eukaryotic factors participating in various stages of the autophagic process. Thus far 34 Atgs have been identified in yeast, including the key autophagic protein Atg8. The Atg8 gene family encodes ubiquitin-like proteins that share a similar structure consisting of two amino-terminal α helices and a ubiquitin-like core. Atg8 family members are expressed in various tissues, where they participate in multiple cellular processes, such as intracellular membrane trafficking and autophagy. Their role in autophagy has been intensively studied. Atg8 proteins undergo a unique ubiquitin-like conjugation to phosphatidylethanolamine on the autophagic membrane, a process essential for autophagosome formation. Whereas yeast has a single Atg8 gene, many other eukaryotes contain multiple Atg8 orthologs. Atg8 genes of multicellular animals can be divided, by sequence similarities, into three subfamilies: microtubule-associated protein 1 light chain 3 (MAP1LC3 or LC3), γ-aminobutyric acid receptor-associated protein (GABARAP) and Golgi-associated ATPase enhancer of 16 kDa (GATE-16), which are present in sponges, cnidarians (such as sea anemones, corals and hydras) and bilateral animals. Although genes from all three subfamilies are found in vertebrates, some invertebrate lineages have lost the genes from one or two subfamilies. The amino terminus of Atg8 proteins varies between the subfamilies and has a regulatory role in their various functions. Here we discuss the evolution of Atg8 proteins and summarize the current view of their function in intracellular trafficking and autophagy from a structural perspective.}, } @article {pmid21864651, year = {2012}, author = {Chen, J and Enns, CA}, title = {Hereditary hemochromatosis and transferrin receptor 2.}, journal = {Biochimica et biophysica acta}, volume = {1820}, number = {3}, pages = {256-263}, pmid = {21864651}, issn = {0006-3002}, support = {R01 DK072166/DK/NIDDK NIH HHS/United States ; NIHDK072166//PHS HHS/United States ; R37 DK054488/DK/NIDDK NIH HHS/United States ; R01 DK072166-05/DK/NIDDK NIH HHS/United States ; R37 DK054488-10/DK/NIDDK NIH HHS/United States ; }, mesh = {Anemia, Iron-Deficiency/genetics/metabolism ; Antimicrobial Cationic Peptides/*metabolism ; Cation Transport Proteins/metabolism ; Erythropoiesis/genetics ; Hemochromatosis/*genetics/metabolism ; Hepcidins ; Humans ; Intestinal Mucosa/metabolism ; Ion Transport ; Iron/*metabolism ; Liver/metabolism ; Macrophages/metabolism ; Receptors, Transferrin/*genetics/metabolism ; }, abstract = {BACKGROUND: Multicellular organisms regulate the uptake of calories, trace elements, and other nutrients by complex feedback mechanisms. In the case of iron, the body senses internal iron stores, iron requirements for hematopoiesis, and inflammatory status, and regulates iron uptake by modulating the uptake of dietary iron from the intestine. Both the liver and the intestine participate in the coordination of iron uptake and distribution in the body. The liver senses inflammatory signals and iron status of the organism and secretes a peptide hormone, hepcidin. Under high iron or inflammatory conditions hepcidin levels increase. Hepcidin binds to the iron transport protein, ferroportin (FPN), promoting FPN internalization and degradation. Decreased FPN levels reduce iron efflux out of intestinal epithelial cells and macrophages into the circulation. Derangements in iron metabolism result in either the abnormal accumulation of iron in the body, or in anemias. The identification of the mutations that cause the iron overload disease, hereditary hemochromatosis (HH), or iron-refractory iron-deficiency anemia has revealed many of the proteins used to regulate iron uptake.

SCOPE OF THE REVIEW: In this review we discuss recent data concerning the regulation of iron homeostasis in the body by the liver and how transferrin receptor 2 (TfR2) affects this process.

MAJOR CONCLUSIONS: TfR2 plays a key role in regulating iron homeostasis in the body.

GENERAL SIGNIFICANCE: The regulation of iron homeostasis is important. One third of the people in the world are anemic. HH is the most common inherited disease in people of Northern European origin and can lead to severe health complications if left untreated. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders.}, } @article {pmid21857801, year = {2011}, author = {Koschwanez, JH and Foster, KR and Murray, AW}, title = {Sucrose utilization in budding yeast as a model for the origin of undifferentiated multicellularity.}, journal = {PLoS biology}, volume = {9}, number = {8}, pages = {e1001122}, pmid = {21857801}, issn = {1545-7885}, support = {P50 GM068763/GM/NIGMS NIH HHS/United States ; 242670/ERC_/European Research Council/International ; K25 GM085806/GM/NIGMS NIH HHS/United States ; GM068763/GM/NIGMS NIH HHS/United States ; K25GM085806/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Adhesion/physiology ; Cell Division/physiology ; Glucose/metabolism ; Models, Biological ; Saccharomycetales/*cytology/enzymology/*metabolism ; Sucrose/*metabolism ; beta-Fructofuranosidase/genetics/metabolism ; }, abstract = {We use the budding yeast, Saccharomyces cerevisiae, to investigate one model for the initial emergence of multicellularity: the formation of multicellular aggregates as a result of incomplete cell separation. We combine simulations with experiments to show how the use of secreted public goods favors the formation of multicellular aggregates. Yeast cells can cooperate by secreting invertase, an enzyme that digests sucrose into monosaccharides, and many wild isolates are multicellular because cell walls remain attached to each other after the cells divide. We manipulate invertase secretion and cell attachment, and show that multicellular clumps have two advantages over single cells: they grow under conditions where single cells cannot and they compete better against cheaters, cells that do not make invertase. We propose that the prior use of public goods led to selection for the incomplete cell separation that first produced multicellularity.}, } @article {pmid21855640, year = {2011}, author = {Liu, F and Li, J and Fu, J and Shen, Y and Xu, X}, title = {Two novel homologs of simple C-type lectin in grass carp (Ctenopharyngodon idellus): potential role in immune response to bacteria.}, journal = {Fish & shellfish immunology}, volume = {31}, number = {6}, pages = {765-773}, doi = {10.1016/j.fsi.2011.07.014}, pmid = {21855640}, issn = {1095-9947}, mesh = {Aeromonas hydrophila/*immunology ; Amino Acid Sequence ; Animals ; Aquaculture ; Base Sequence ; Carps/genetics/*immunology ; China ; DNA Primers/genetics ; DNA, Complementary/genetics ; Gene Expression Profiling/veterinary ; Gene Expression Regulation/*immunology ; Genes, Duplicate/genetics ; Lectins, C-Type/*genetics/metabolism ; Molecular Sequence Data ; *Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction/veterinary ; Sequence Analysis, DNA/veterinary ; Sequence Homology ; }, abstract = {C-type lectins play important roles in glycoprotein metabolism, multicellular integration and immunity. Based on their overall domain structure, they can be classified as different groups which possess different physiological functions. In this study, two novel simple C-type lectins were identified from grass carp (Ctenopharyngodon idellus), an important cultured fish in China. GcCL1 and gcCL2 share an essentially identical gene structure, a conserved promoter region shorter than 300 bp and an amino acid identity of 81.2%. Phylogenetic analysis indicated they may be products of gene duplication and could be classified as a new clade of group VII C-type lectins. Both of them were expressed in the eleven tissues examined, with the spleen having the highest abundance of transcript. The gcCL1 transcript was more abundant than gcCL2 in the majority of tissue samples from 2-yr-old grass carps, and was lower than those of gcCL2 before 15 days post-hatching. The expression of both genes was significantly up-regulated in spleen, muscle, skin, gills and hepatopancreas after induction by Aeromonas hydrophila. This is the first report that the expression of group VII C-type lectins could be induced by a pathogen, and indicates these lectins may be involved in the immune response to bacteria in fish.}, } @article {pmid21849086, year = {2011}, author = {Xie, X and Jin, J and Mao, Y}, title = {Evolutionary versatility of eukaryotic protein domains revealed by their bigram networks.}, journal = {BMC evolutionary biology}, volume = {11}, number = {}, pages = {242}, pmid = {21849086}, issn = {1471-2148}, mesh = {Adaptation, Biological/*genetics ; Cluster Analysis ; Computational Biology/*methods ; Eukaryota/*genetics ; *Evolution, Molecular ; Humans ; *Models, Genetic ; Protein Structure, Tertiary/*genetics ; Proteins/*genetics ; }, abstract = {BACKGROUND: Protein domains are globular structures of independently folded polypeptides that exert catalytic or binding activities. Their sequences are recognized as evolutionary units that, through genome recombination, constitute protein repertoires of linkage patterns. Via mutations, domains acquire modified functions that contribute to the fitness of cells and organisms. Recent studies have addressed the evolutionary selection that may have shaped the functions of individual domains and the emergence of particular domain combinations, which led to new cellular functions in multi-cellular animals. This study focuses on modeling domain linkage globally and investigates evolutionary implications that may be revealed by novel computational analysis.

RESULTS: A survey of 77 completely sequenced eukaryotic genomes implies a potential hierarchical and modular organization of biological functions in most living organisms. Domains in a genome or multiple genomes are modeled as a network of hetero-duplex covalent linkages, termed bigrams. A novel computational technique is introduced to decompose such networks, whereby the notion of domain "networking versatility" is derived and measured. The most and least "versatile" domains (termed "core domains" and "peripheral domains" respectively) are examined both computationally via sequence conservation measures and experimentally using selected domains. Our study suggests that such a versatility measure extracted from the bigram networks correlates with the adaptivity of domains during evolution, where the network core domains are highly adaptive, significantly contrasting the network peripheral domains.

CONCLUSIONS: Domain recombination has played a major part in the evolution of eukaryotes attributing to genome complexity. From a system point of view, as the results of selection and constant refinement, networks of domain linkage are structured in a hierarchical modular fashion. Domains with high degree of networking versatility appear to be evolutionary adaptive, potentially through functional innovations. Domain bigram networks are informative as a model of biological functions. The networking versatility indices extracted from such networks for individual domains reflect the strength of evolutionary selection that the domains have experienced.}, } @article {pmid21840410, year = {2011}, author = {Spaeth, JM and Kim, NH and Boyer, TG}, title = {Mediator and human disease.}, journal = {Seminars in cell & developmental biology}, volume = {22}, number = {7}, pages = {776-787}, pmid = {21840410}, issn = {1096-3634}, support = {R01 AR053100/AR/NIAMS NIH HHS/United States ; R01 MH085320/MH/NIMH NIH HHS/United States ; MH085320/MH/NIMH NIH HHS/United States ; AR053100/AR/NIAMS NIH HHS/United States ; }, mesh = {Cardiovascular Diseases/genetics/*metabolism/pathology ; Female ; Gene Expression Regulation ; Humans ; Male ; Mediator Complex/*genetics/*metabolism ; Mental Disorders/genetics/*metabolism/pathology ; Neoplasms/genetics/*metabolism/pathology ; Neoplasms, Hormone-Dependent/genetics/metabolism/pathology ; Nervous System Diseases/genetics/*metabolism/pathology ; Protein Subunits ; RNA Polymerase II/chemistry/genetics/metabolism ; Signal Transduction ; Transcription Factors ; }, abstract = {Since the identification of a metazoan counterpart to yeast Mediator nearly 15 years ago, a convergent body of biochemical and molecular genetic studies have confirmed their structural and functional relationship as an integrative hub through which regulatory information conveyed by signal activated transcription factors is transduced to RNA polymerase II. Nonetheless, metazoan Mediator complexes have been shaped during evolution by substantive diversification and expansion in both the number and sequence of their constituent subunits, with important implications for the development of multicellular organisms. The appearance of unique interaction surfaces within metazoan Mediator complexes for transcription factors of diverse species-specific origins extended the role of Mediator to include an essential function in coupling developmentally coded signals with precise gene expression output sufficient to specify cell fate and function. The biological significance of Mediator in human development, suggested by genetic studies in lower metazoans, is emphatically illustrated by an expanding list of human pathologies linked to genetic variation or aberrant expression of its individual subunits. Here, we review our current body of knowledge concerning associations between individual Mediator subunits and specific pathological disorders. When established, molecular etiologies underlying genotype-phenotype correlations are addressed, and we anticipate that future progress in this critical area will help identify therapeutic targets across a range of human pathologies.}, } @article {pmid21818306, year = {2011}, author = {Tarrío, R and Ayala, FJ and Rodríguez-Trelles, F}, title = {The Vein Patterning 1 (VEP1) gene family laterally spread through an ecological network.}, journal = {PloS one}, volume = {6}, number = {7}, pages = {e22279}, pmid = {21818306}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Catalytic Domain ; *Ecosystem ; Eukaryota/*genetics ; Gene Transfer, Horizontal/*genetics ; Likelihood Functions ; Molecular Sequence Data ; Multigene Family/*genetics ; Phylogeny ; Prokaryotic Cells/*metabolism ; Proteins/chemistry/genetics ; Sequence Homology, Nucleic Acid ; }, abstract = {Lateral gene transfer (LGT) is a major evolutionary mechanism in prokaryotes. Knowledge about LGT--particularly, multicellular--eukaryotes has only recently started to accumulate. A widespread assumption sees the gene as the unit of LGT, largely because little is yet known about how LGT chances are affected by structural/functional features at the subgenic level. Here we trace the evolutionary trajectory of VEin Patterning 1, a novel gene family known to be essential for plant development and defense. At the subgenic level VEP1 encodes a dinucleotide-binding Rossmann-fold domain, in common with members of the short-chain dehydrogenase/reductase (SDR) protein family. We found: i) VEP1 likely originated in an aerobic, mesophilic and chemoorganotrophic α-proteobacterium, and was laterally propagated through nets of ecological interactions, including multiple LGTs between phylogenetically distant green plant/fungi-associated bacteria, and five independent LGTs to eukaryotes. Of these latest five transfers, three are ancient LGTs, implicating an ancestral fungus, the last common ancestor of land plants and an ancestral trebouxiophyte green alga, and two are recent LGTs to modern embryophytes. ii) VEP1's rampant LGT behavior was enabled by the robustness and broad utility of the dinucleotide-binding Rossmann-fold, which provided a platform for the evolution of two unprecedented departures from the canonical SDR catalytic triad. iii) The fate of VEP1 in eukaryotes has been different in different lineages, being ubiquitous and highly conserved in land plants, whereas fungi underwent multiple losses. And iv) VEP1-harboring bacteria include non-phytopathogenic and phytopathogenic symbionts which are non-randomly distributed with respect to the type of harbored VEP1 gene. Our findings suggest that VEP1 may have been instrumental for the evolutionary transition of green plants to land, and point to a LGT-mediated 'Trojan Horse' mechanism for the evolution of bacterial pathogenesis against plants. VEP1 may serve as tool for revealing microbial interactions in plant/fungi-associated environments.}, } @article {pmid21818295, year = {2011}, author = {Frieden, BR and Gatenby, RA}, title = {Information dynamics in living systems: prokaryotes, eukaryotes, and cancer.}, journal = {PloS one}, volume = {6}, number = {7}, pages = {e22085}, pmid = {21818295}, issn = {1932-6203}, support = {U54 CA143970/CA/NCI NIH HHS/United States ; 1U54CA143970-01/CA/NCI NIH HHS/United States ; }, mesh = {Cell Proliferation ; Entropy ; Eukaryotic Cells/*metabolism ; Glycolysis ; Humans ; *Information Theory ; Neoplasms/*metabolism/pathology ; Prokaryotic Cells/*metabolism ; }, abstract = {BACKGROUND: Living systems use information and energy to maintain stable entropy while far from thermodynamic equilibrium. The underlying first principles have not been established.

FINDINGS: We propose that stable entropy in living systems, in the absence of thermodynamic equilibrium, requires an information extremum (maximum or minimum), which is invariant to first order perturbations. Proliferation and death represent key feedback mechanisms that promote stability even in a non-equilibrium state. A system moves to low or high information depending on its energy status, as the benefit of information in maintaining and increasing order is balanced against its energy cost. Prokaryotes, which lack specialized energy-producing organelles (mitochondria), are energy-limited and constrained to an information minimum. Acquisition of mitochondria is viewed as a critical evolutionary step that, by allowing eukaryotes to achieve a sufficiently high energy state, permitted a phase transition to an information maximum. This state, in contrast to the prokaryote minima, allowed evolution of complex, multicellular organisms. A special case is a malignant cell, which is modeled as a phase transition from a maximum to minimum information state. The minimum leads to a predicted power-law governing the in situ growth that is confirmed by studies measuring growth of small breast cancers.

CONCLUSIONS: We find living systems achieve a stable entropic state by maintaining an extreme level of information. The evolutionary divergence of prokaryotes and eukaryotes resulted from acquisition of specialized energy organelles that allowed transition from information minima to maxima, respectively. Carcinogenesis represents a reverse transition: of an information maximum to minimum. The progressive information loss is evident in accumulating mutations, disordered morphology, and functional decline characteristics of human cancers. The findings suggest energy restriction is a critical first step that triggers the genetic mutations that drive somatic evolution of the malignant phenotype.}, } @article {pmid21815659, year = {2011}, author = {Ngo, JT and Tirrell, DA}, title = {Noncanonical amino acids in the interrogation of cellular protein synthesis.}, journal = {Accounts of chemical research}, volume = {44}, number = {9}, pages = {677-685}, pmid = {21815659}, issn = {1520-4898}, support = {R01 GM062523/GM/NIGMS NIH HHS/United States ; R01 GM062523-07/GM/NIGMS NIH HHS/United States ; GM 62523/GM/NIGMS NIH HHS/United States ; }, mesh = {Alkenes/chemistry ; Alkynes/chemistry/metabolism ; Amino Acids/chemistry/*metabolism ; Amino Acyl-tRNA Synthetases/genetics/metabolism ; Azides/chemistry ; Catalysis ; Copper/chemistry ; Fluorescent Dyes/chemistry ; Glycine/analogs & derivatives/chemistry/metabolism ; Mass Spectrometry ; Microscopy, Fluorescence ; Mutation ; *Protein Biosynthesis ; Proteins/chemistry/*metabolism ; }, abstract = {Proteins in living cells can be made receptive to bioorthogonal chemistries through metabolic labeling with appropriately designed noncanonical amino acids (ncAAs). In the simplest approach to metabolic labeling, an amino acid analog replaces one of the natural amino acids specified by the protein's gene (or genes) of interest. Through manipulation of experimental conditions, the extent of the replacement can be adjusted. This approach, often termed residue-specific incorporation, allows the ncAA to be incorporated in controlled proportions into positions normally occupied by the natural amino acid residue. For a protein to be labeled in this way with an ncAA, it must fulfill just two requirements: (i) the corresponding natural amino acid must be encoded within the sequence of the protein at the genetic level, and (ii) the protein must be expressed while the ncAA is in the cell. Because this approach permits labeling of proteins throughout the cell, it has enabled us to develop strategies to track cellular protein synthesis by tagging proteins with reactive ncAAs. In procedures similar to isotopic labeling, translationally active ncAAs are incorporated into proteins during a "pulse" in which newly synthesized proteins are tagged. The set of tagged proteins can be distinguished from those made before the pulse by bioorthogonally ligating the ncAA side chain to probes that permit detection, isolation, and visualization of the labeled proteins. Noncanonical amino acids with side chains containing azide, alkyne, or alkene groups have been especially useful in experiments of this kind. They have been incorporated into proteins in the form of methionine analogs that are substrates for the natural translational machinery. The selectivity of the method can be enhanced through the use of mutant aminoacyl tRNA synthetases (aaRSs) that permit incorporation of ncAAs not used by the endogenous biomachinery. Through expression of mutant aaRSs, proteins can be tagged with other useful ncAAs, including analogs that contain ketones or aryl halides. High-throughput screening strategies can identify aaRS variants that activate a wide range of ncAAs. Controlled expression of mutant synthetases has been combined with ncAA tagging to permit cell-selective metabolic labeling of proteins. Expression of a mutant synthetase in a portion of cells within a complex cellular mixture restricts labeling to that subset of cells. Proteins synthesized in cells not expressing the synthetase are neither labeled nor detected. In multicellular environments, this approach permits the identification of the cellular origins of labeled proteins. In this Account, we summarize the tools and strategies that have been developed for interrogating cellular protein synthesis through residue-specific tagging with ncAAs. We describe the chemical and genetic components of ncAA-tagging strategies and discuss how these methods are being used in chemical biology.}, } @article {pmid21813465, year = {2012}, author = {Kwantes, M and Liebsch, D and Verelst, W}, title = {How MIKC* MADS-box genes originated and evidence for their conserved function throughout the evolution of vascular plant gametophytes.}, journal = {Molecular biology and evolution}, volume = {29}, number = {1}, pages = {293-302}, doi = {10.1093/molbev/msr200}, pmid = {21813465}, issn = {1537-1719}, mesh = {Amino Acid Sequence ; Arabidopsis/genetics ; *Evolution, Molecular ; Gene Duplication ; *Genes, Plant ; Germ Cells, Plant/*physiology ; MADS Domain Proteins/*genetics ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; }, abstract = {Land plants have a remarkable life cycle that alternates between a diploid sporophytic and a haploid gametophytic generation, both of which are multicellular and changed drastically during evolution. Classical MIKC MADS-domain (MIKCC) transcription factors are famous for their role in sporophytic development and are considered crucial for its evolution. About the regulation of gametophyte development, in contrast, little is known. Recent evidence indicated that the closely related MIKC* MADS-domain proteins are important for the functioning of the Arabidopsis thaliana male gametophyte (pollen). Furthermore, also in bryophytes, several MIKC* genes are expressed in the haploid generation. Therefore, that MIKC* genes have a similar role in the evolution of the gametophytic phase as MIKCC genes have in the sporophyte is a tempting hypothesis. To get a comprehensive view of the involvement of MIKC* genes in gametophyte evolution, we isolated them from a broad variety of vascular plants, including the lycophyte Selaginella moellendorffii, the fern Ceratopteris richardii, and representatives of several flowering plant lineages. Phylogenetic analysis revealed an extraordinary conservation not found in MIKCC genes. Moreover, expression and interaction studies suggest that a conserved and characteristic network operates in the gametophytes of all tested model organisms. Additionally, we found that MIKC* genes probably evolved from an ancestral MIKCC-like gene by a duplication in the Keratin-like region. We propose that this event facilitated the independent evolution of MIKC* and MIKCC protein networks and argue that whereas MIKCC genes diversified and attained new functions, MIKC* genes retained a conserved role in the gametophyte during land plant evolution.}, } @article {pmid21802297, year = {2011}, author = {Jiang, C and Mithani, A and Gan, X and Belfield, EJ and Klingler, JP and Zhu, JK and Ragoussis, J and Mott, R and Harberd, NP}, title = {Regenerant Arabidopsis lineages display a distinct genome-wide spectrum of mutations conferring variant phenotypes.}, journal = {Current biology : CB}, volume = {21}, number = {16}, pages = {1385-1390}, pmid = {21802297}, issn = {1879-0445}, support = {090532/WT_/Wellcome Trust/United Kingdom ; BB/F020759/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/F022697/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Arabidopsis/anatomy & histology/*genetics ; Base Sequence ; DNA Mutational Analysis ; DNA Transposable Elements ; *Genome, Plant ; Molecular Sequence Data ; *Mutation ; Mutation Rate ; *Phenotype ; Regeneration/*physiology ; Sequence Alignment ; }, abstract = {Multicellular organisms can be regenerated from totipotent differentiated somatic cell or nuclear founders [1-3]. Organisms regenerated from clonally related isogenic founders might a priori have been expected to be phenotypically invariant. However, clonal regenerant animals display variant phenotypes caused by defective epigenetic reprogramming of gene expression [2], and clonal regenerant plants exhibit poorly understood heritable phenotypic ("somaclonal") variation [4-7]. Here we show that somaclonal variation in regenerant Arabidopsis lineages is associated with genome-wide elevation in DNA sequence mutation rate. We also show that regenerant mutations comprise a distinctive molecular spectrum of base substitutions, insertions, and deletions that probably results from decreased DNA repair fidelity. Finally, we show that while regenerant base substitutions are a likely major genetic cause of the somaclonal variation of regenerant Arabidopsis lineages, transposon movement is unlikely to contribute substantially to that variation. We conclude that the phenotypic variation of regenerant plants, unlike that of regenerant animals, is substantially due to DNA sequence mutation.}, } @article {pmid21795732, year = {2011}, author = {Talianova, M and Janousek, B}, title = {What can we learn from tobacco and other Solanaceae about horizontal DNA transfer?.}, journal = {American journal of botany}, volume = {98}, number = {8}, pages = {1231-1242}, doi = {10.3732/ajb.1000370}, pmid = {21795732}, issn = {1537-2197}, mesh = {Agrobacterium/genetics ; Cell Nucleus/genetics ; Chloroplasts/genetics ; DNA, Bacterial/*genetics ; DNA, Chloroplast/genetics ; DNA, Fungal/*genetics ; DNA, Plant/*genetics ; DNA, Viral/genetics ; Evolution, Molecular ; *Gene Transfer, Horizontal ; Mycorrhizae/genetics ; Plant Viruses/genetics ; Solanaceae/*genetics/microbiology/virology ; Tobacco/*genetics/microbiology/virology ; Transformation, Genetic ; }, abstract = {In eukaryotic organisms, horizontal gene transfer (HGT) is regarded as an important though infrequent source of reticulate evolution. Many confirmed instances of natural HGT involving multicellular eukaryotes come from flowering plants. This review intends to provide a synthesis of present knowledge regarding HGT in higher plants, with an emphasis on tobacco and other species in the Solanaceae family because there are numerous detailed reports concerning natural HGT events, involving various donors, in this family. Moreover, in-depth experimental studies using transgenic tobacco are of great importance for understanding this process. Valuable insights are offered concerning the mechanisms of HGT, the adaptive role and regulation of natural transgenes, and new routes for gene trafficking. With an increasing amount of data on HGT, a synthetic view is beginning to emerge.}, } @article {pmid21791580, year = {2011}, author = {Brazelton, WJ and Mehta, MP and Kelley, DS and Baross, JA}, title = {Physiological differentiation within a single-species biofilm fueled by serpentinization.}, journal = {mBio}, volume = {2}, number = {4}, pages = {}, pmid = {21791580}, issn = {2150-7511}, mesh = {Biofilms/*growth & development ; DNA, Archaeal/chemistry/genetics ; Genes, Archaeal ; Hot Springs/*microbiology ; Hot Temperature ; Hydrogen/metabolism ; Hydrogen-Ion Concentration ; Intracellular Membranes/ultrastructure ; Metabolic Networks and Pathways/genetics ; Metagenome ; Methane/metabolism ; Methanosarcinales/*cytology/growth & development/metabolism/*physiology ; Microscopy, Electron, Transmission ; Molecular Sequence Data ; Oxidation-Reduction ; Sequence Analysis, DNA ; }, abstract = {UNLABELLED: Carbonate chimneys at the Lost City hydrothermal field are coated in biofilms dominated by a single phylotype of archaea known as Lost City Methanosarcinales. In this study, we have detected surprising physiological complexity in single-species biofilms, which is typically indicative of multispecies biofilm communities. Multiple cell morphologies were visible within the biofilms by transmission electron microscopy, and some cells contained intracellular membranes that may facilitate methane oxidation. Both methane production and oxidation were detected at 70 to 80°C and pH 9 to 10 in samples containing the single-species biofilms. Both processes were stimulated by the presence of hydrogen (H(2)), indicating that methane production and oxidation are part of a syntrophic interaction. Metagenomic data included a sequence encoding AMP-forming acetyl coenzyme A synthetase, indicating that acetate may play a role in the methane-cycling syntrophy. A wide range of nitrogen fixation genes were also identified, many of which were likely acquired via lateral gene transfer (LGT). Our results indicate that cells within these single-species biofilms may have differentiated into multiple physiological roles to form multicellular communities linked by metabolic interactions and LGT. Communities similar to these Lost City biofilms are likely to have existed early in the evolution of life, and we discuss how the multicellular characteristics of ancient hydrogen-fueled biofilm communities could have stimulated ecological diversification, as well as unity of biochemistry, during the earliest stages of cellular evolution.

IMPORTANCE: Our previous work at the Lost City hydrothermal field has shown that its carbonate chimneys host microbial biofilms dominated by a single uncultivated "species" of archaea. In this paper, we integrate evidence from these previous studies with new data on the metabolic activity and cellular morphology of these archaeal biofilms. We conclude that the archaeal biofilm must contain cells that are physiologically and possibly genetically differentiated with respect to each other. These results are especially interesting considering the possibility that the first cells originated and evolved in hydrothermal systems similar to Lost City.}, } @article {pmid21781968, year = {2011}, author = {Ottaviani, E and Malagoli, D and Franceschi, C}, title = {The evolution of the adipose tissue: a neglected enigma.}, journal = {General and comparative endocrinology}, volume = {174}, number = {1}, pages = {1-4}, doi = {10.1016/j.ygcen.2011.06.018}, pmid = {21781968}, issn = {1095-6840}, mesh = {Adipose Tissue/*metabolism ; Adipose Tissue, White/metabolism ; Animals ; *Biological Evolution ; Humans ; Invertebrates/classification/metabolism ; Vertebrates/classification/metabolism ; }, abstract = {The complexity of the anatomical distribution and functions of adipose tissue (AT) has been rarely analyzed in an evolutionary perspective. From yeast to man lipid droplets are stored mainly in the form of triglycerides in order to provide energy during periods when energy demands exceed caloric intake. This simple scenario is in agreement with the recent discovery of a highly conserved family of proteins for fat storage in both unicellular and multicellular organisms. However, the evolutionary history of organs such as the fat body in insects, playing a role in immunity and other functions besides energy storage and thermal insulation, and of differently distributed subtypes of AT in vertebrates is much less clear. These topics still await a systematic investigation using up-to-date technologies and approaches that would provide information useful for understanding the role of different AT subtypes in normal/physiological conditions or in metabolic pathologies of humans.}, } @article {pmid21779277, year = {2011}, author = {Müller, J and Overmann, J}, title = {Close Interspecies Interactions between Prokaryotes from Sulfureous Environments.}, journal = {Frontiers in microbiology}, volume = {2}, number = {}, pages = {146}, pmid = {21779277}, issn = {1664-302X}, abstract = {Green sulfur bacteria are obligate photolithoautotrophs that require highly reducing conditions for growth and can utilize only a very limited number of carbon substrates. These bacteria thus inhabit a very narrow ecologic niche. However, several green sulfur bacteria have overcome the limits of immobility by entering into a symbiosis with motile Betaproteobacteria in a type of multicellular association termed phototrophic consortia. One of these consortia, "Chlorochromatium aggregatum," has recently been established as the first culturable model system to elucidate the molecular basis of this symbiotic interaction. It consists of 12-20 green sulfur bacteria epibionts surrounding a central, chemoheterotrophic betaproteobacterium in a highly ordered fashion. Recent genomic, transcriptomic, and proteomic studies of "C. aggregatum" and its epibiont provide insights into the molecular basis and the origin of the stable association between the two very distantly related bacteria. While numerous genes of central metabolic pathways are upregulated during the specific symbiosis and hence involved in the interaction, only a limited number of unique putative symbiosis genes have been detected in the epibiont. Green sulfur bacteria therefore are preadapted to a symbiotic lifestyle. The metabolic coupling between the bacterial partners appears to involve amino acids and highly specific ultrastructures at the contact sites between the cells. Similarly, the interaction in the equally well studied archaeal consortia consisting of Nanoarchaeum equitans and its host Ignicoccus hospitalis is based on the transfer of amino acids while lacking the highly specialized contact sites observed in phototrophic consortia.}, } @article {pmid21777854, year = {2011}, author = {Wu, Y and Yuan, H and Tan, S and Chen, JQ and Tian, D and Yang, H}, title = {Increased complexity of gene structure and base composition in vertebrates.}, journal = {Journal of genetics and genomics = Yi chuan xue bao}, volume = {38}, number = {7}, pages = {297-305}, doi = {10.1016/j.jgg.2011.06.004}, pmid = {21777854}, issn = {1673-8527}, mesh = {3' Untranslated Regions/genetics ; 5' Untranslated Regions/genetics ; Animals ; Base Composition/*genetics ; Computational Biology ; *Evolution, Molecular ; Exons/genetics ; GC Rich Sequence/genetics ; Genome ; Humans ; Introns/genetics ; *Sequence Homology, Amino Acid ; Vertebrates/*genetics ; }, abstract = {How the structure and base composition of genes changed with the evolution of vertebrates remains a puzzling question. Here we analyzed 895 orthologous protein-coding genes in six multicellular animals: human, chicken, zebrafish, sea squirt, fruit fly, and worm. Our analyses reveal that many gene regions, particularly intron and 3' UTR, gradually expanded throughout the evolution of vertebrates from their invertebrate ancestors, and that the number of exons per gene increased. Studies based on all protein-coding genes in each genome provide consistent results. We also find that GC-content increased in many gene regions (especially 5' UTR) in the evolution of endotherms, except in coding-exons. Analysis of individual genomes shows that 3' UTR demonstrated stronger length and GC-content correlation with intron than 5' UTR, and gene with large intron in all six species demonstrated relatively similar GC-content. Our data indicates a great increase in complexity in vertebrate genes and we propose that the requirement for morphological and functional changes is probably the driving force behind the evolution of structure and base composition complexity in multicellular animal genes.}, } @article {pmid21766126, year = {2012}, author = {Nussinov, R}, title = {How do dynamic cellular signals travel long distances?.}, journal = {Molecular bioSystems}, volume = {8}, number = {1}, pages = {22-26}, pmid = {21766126}, issn = {1742-2051}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; Z01 BC010440//Intramural NIH HHS/United States ; }, mesh = {Animals ; Cells/*metabolism ; Humans ; Protein Conformation ; Protein Folding ; Proteins/chemistry/metabolism ; *Signal Transduction ; }, abstract = {Communication is essential. It is vital between cells in multi-cellular organisms, and within cells. A signaling molecule binds to a receptor protein, and initiates a cascade of dynamic events. Signaling is a multistep pathway, which allows signal amplification: if some of the molecules in a pathway transmit the signal to multiple molecules, the result can be a large number of activated molecules across the cell and multiple reactions. That is how a small number of extracellular signaling molecules can produce a major cellular response. The pathway can relay signals from the extracellular space to the nucleus. How do signals travel efficiently over long-distances across the cell? Here we argue that evolution has utilized three properties: a modular functional organization of the cellular network; sequences in some key regions of proteins, such as linkers or loops, which were pre-encoded by evolution to facilitate signaling among domains; and compact interactions between proteins which is achieved via conformational disorder.}, } @article {pmid21763530, year = {2011}, author = {Costas, C and Sanchez, Mde L and Sequeira-Mendes, J and Gutierrez, C}, title = {Progress in understanding DNA replication control.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {181}, number = {3}, pages = {203-209}, doi = {10.1016/j.plantsci.2011.04.020}, pmid = {21763530}, issn = {1873-2259}, mesh = {Arabidopsis/genetics/metabolism ; Cell Cycle/genetics/physiology ; Chromatin/metabolism ; Chromosome Duplication ; *DNA Replication ; DNA, Plant/*genetics ; Epigenomics ; Gene Expression Regulation, Plant ; Plants/*genetics/metabolism ; Replication Origin ; }, abstract = {Completion of genome duplication during the S-phase of the cell cycle is crucial for the maintenance of genomic integrity. In eukaryotes, chromosomal DNA replication is accomplished by the activity of multiple origins of DNA replication scattered across the genome. Origin specification, selection and activity as well as the availability of replication factors and the regulation of DNA replication licensing, have unique and common features among eukaryotes. Although the initial studies on the semiconservative nature of chromosome duplication were carried out in the mid 1950s in Vicia faba, since then plant DNA replication studies have been scarce. However, they have received an unprecedented drive in the last decade after the completion of sequencing the Arabidopsis thaliana genome, and more recently of other plant genomes. In particular, the past year has witnessed major advances with the use of genomic approaches to study chromosomal replication timing, DNA replication origins and licensing control mechanisms. In this minireview article we discuss these recent discoveries in plants in the context of what is known at the genomic level in other eukaryotes. These studies constitute the basis for addressing in the future key questions about replication origin specification and function that will be of relevance not only for plants but also for the rest of multicellular organisms.}, } @article {pmid21757610, year = {2011}, author = {Heidel, AJ and Lawal, HM and Felder, M and Schilde, C and Helps, NR and Tunggal, B and Rivero, F and John, U and Schleicher, M and Eichinger, L and Platzer, M and Noegel, AA and Schaap, P and Glöckner, G}, title = {Phylogeny-wide analysis of social amoeba genomes highlights ancient origins for complex intercellular communication.}, journal = {Genome research}, volume = {21}, number = {11}, pages = {1882-1891}, pmid = {21757610}, issn = {1549-5469}, support = {BB/D013453/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/E016308/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/E016308//BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence/genetics ; Base Composition ; Biological Transport ; Cell Adhesion/genetics ; Cell Communication/genetics ; Cell Movement/genetics ; Centromere/genetics/metabolism ; Cytoskeleton/genetics ; Dictyostelium/*genetics/metabolism ; Evolution, Molecular ; *Genome, Protozoan ; Molecular Sequence Data ; Molecular Structure ; Nucleotides, Cyclic/metabolism ; Open Reading Frames ; *Phylogeny ; Protein Interaction Domains and Motifs ; Signal Transduction ; Synteny ; Telomere/genetics/metabolism ; Transcription, Genetic ; }, abstract = {Dictyostelium discoideum (DD), an extensively studied model organism for cell and developmental biology, belongs to the most derived group 4 of social amoebas, a clade of altruistic multicellular organisms. To understand genome evolution over long time periods and the genetic basis of social evolution, we sequenced the genomes of Dictyostelium fasciculatum (DF) and Polysphondylium pallidum (PP), which represent the early diverging groups 1 and 2, respectively. In contrast to DD, PP and DF have conventional telomere organization and strongly reduced numbers of transposable elements. The number of protein-coding genes is similar between species, but only half of them comprise an identifiable set of orthologous genes. In general, genes involved in primary metabolism, cytoskeletal functions and signal transduction are conserved, while genes involved in secondary metabolism, export, and signal perception underwent large differential gene family expansions. This most likely signifies involvement of the conserved set in core cell and developmental mechanisms, and of the diverged set in niche- and species-specific adaptations for defense and food, mate, and kin selection. Phylogenetic dating using a concatenated data set and extensive loss of synteny indicate that DF, PP, and DD split from their last common ancestor at least 0.6 billion years ago.}, } @article {pmid21756106, year = {2011}, author = {Lynch, M and Bobay, LM and Catania, F and Gout, JF and Rho, M}, title = {The repatterning of eukaryotic genomes by random genetic drift.}, journal = {Annual review of genomics and human genetics}, volume = {12}, number = {}, pages = {347-366}, pmid = {21756106}, issn = {1545-293X}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; R01-GM036827/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Eukaryota/*genetics ; *Genetic Drift ; *Genome ; Humans ; Mutation ; Proteins/genetics ; }, abstract = {Recent observations on rates of mutation, recombination, and random genetic drift highlight the dramatic ways in which fundamental evolutionary processes vary across the divide between unicellular microbes and multicellular eukaryotes. Moreover, population-genetic theory suggests that the range of variation in these parameters is sufficient to explain the evolutionary diversification of many aspects of genome size and gene structure found among phylogenetic lineages. Most notably, large eukaryotic organisms that experience elevated magnitudes of random genetic drift are susceptible to the passive accumulation of mutationally hazardous DNA that would otherwise be eliminated by efficient selection. Substantial evidence also suggests that variation in the population-genetic environment influences patterns of protein evolution, with the emergence of certain kinds of amino-acid substitutions and protein-protein complexes only being possible in populations with relatively small effective sizes. These observations imply that the ultimate origins of many of the major genomic and proteomic disparities between prokaryotes and eukaryotes and among eukaryotic lineages have been molded as much by intrinsic variation in the genetic and cellular features of species as by external ecological forces.}, } @article {pmid21755049, year = {2011}, author = {Eirín-López, JM and Ausió, J}, title = {Boule and the Evolutionary Origin of Metazoan Gametogenesis: A Grandpa's Tale.}, journal = {International journal of evolutionary biology}, volume = {2011}, number = {}, pages = {972457}, pmid = {21755049}, issn = {2090-052X}, abstract = {The evolution of sex remains a hotly debated topic in evolutionary biology. In particular, studying the origins of the molecular mechanisms underlying sexual reproduction and gametogenesis (its fundamental component) in multicellular eukaryotes has been difficult due to the rapid divergence of many reproductive proteins, pleiotropy, and by the fact that only a very small number of reproductive proteins specifically involved in reproduction are conserved across lineages. Consequently, during the last decade, many efforts have been put into answering the following question: did gametogenesis evolve independently in different animal lineages or does it share a common evolutionary origin in a single ancestral prototype? Among the various approaches carried out in order to solve this question, the characterization of the evolution of the DAZ gene family holds much promise because these genes encode reproductive proteins that are conserved across a wide range of animal phyla. Within this family, BOULE is of special interest because it represents the most ancestral member of this gene family (the "grandfather" of DAZ). Furthermore, BOULE has attracted most of the attention since it represents an ancient male gametogenic factor with an essential reproductive-exclusive requirement in urbilaterians, constituting a core component of the reproductive prototype. Within this context, the aim of the present work is to provide an up-to-date insight into the studies that lead to the characterization of the DAZ family members and the implications in helping decipher the evolutionary origin of gametogenesis in metazoan animals.}, } @article {pmid21740565, year = {2011}, author = {Courtiade, J and Pauchet, Y and Vogel, H and Heckel, DG}, title = {A comprehensive characterization of the caspase gene family in insects from the order Lepidoptera.}, journal = {BMC genomics}, volume = {12}, number = {}, pages = {357}, pmid = {21740565}, issn = {1471-2164}, mesh = {Amino Acid Sequence ; Animals ; Caspase 1/analysis/classification/genetics ; Caspase 3/analysis/classification/genetics ; Caspase 6/analysis/classification/genetics ; Caspases/analysis/classification/*genetics ; Drosophila/enzymology/genetics ; Expressed Sequence Tags ; Lepidoptera/*enzymology/genetics ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Sequence Alignment ; }, abstract = {BACKGROUND: The cell suicide pathway of apoptosis is a necessary event in the life of multicellular organisms. It is involved in many biological processes ranging from development to the immune response. Evolutionarily conserved proteases, called caspases, play a central role in regulating apoptosis. Reception of death stimuli triggers the activation of initiator caspases, which in turn activate the effector caspases. In Lepidoptera, apoptosis is crucial in processes such as metamorphosis or defending against baculovirus infection. The discovery of p35, a baculovirus protein inhibiting caspase activity, has led to the characterization of the first lepidopteran caspase, Sf-Caspase-1. Studies on Sf-Caspase-1 mode of activation suggested that apoptosis in Lepidoptera requires a cascade of caspase activation, as demonstrated in many other species.

RESULTS: In order to get insights into this gene family in Lepidoptera, we performed an extensive survey of lepidopteran-derived EST datasets. We identified 66 sequences distributed among 27 species encoding putative caspases. Phylogenetic analyses showed that Lepidoptera possess at least 5 caspases, for which we propose a unified nomenclature. According to homology to their Drosophila counterparts and their primary structure, we determined that Lep-Caspase-1, -2 and -3 are putative effector caspases, whereas Lep-Caspase-5 and -6 are putative initiators. The likely function of Lep-Caspase-4 remains unclear. Lep-Caspase-2 is absent from the silkworm genome and appears to be noctuid-specific, and to have arisen from a tandem duplication of the Caspase-1 gene. In the tobacco hawkmoth, 3 distinct transcripts encoding putative Caspase-4 were identified, suggesting at least 2 duplication events in this species.

CONCLUSIONS: The basic repertoire of five major types of caspases shared among Lepidoptera seems to be smaller than for most other groups studied to date, but gene duplication still plays a role in lineage-specific increases in diversity, just as in Diptera and mammals.}, } @article {pmid21726329, year = {2011}, author = {Jarvis, JP and Cropp, SN and Vaughn, TT and Pletscher, LS and King-Ellison, K and Adams-Hunt, E and Erickson, C and Cheverud, JM}, title = {The effect of a population bottleneck on the evolution of genetic variance/covariance structure.}, journal = {Journal of evolutionary biology}, volume = {24}, number = {10}, pages = {2139-2152}, doi = {10.1111/j.1420-9101.2011.02347.x}, pmid = {21726329}, issn = {1420-9101}, support = {R24 RR015116/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Female ; *Genetic Variation ; Inbreeding ; Male ; Mice ; *Models, Genetic ; Multivariate Analysis ; Population Dynamics ; Selection, Genetic ; }, abstract = {It is well known that standard population genetic theory predicts decreased additive genetic variance (V(a)) following a population bottleneck and that theoretical models including interallelic and intergenic interactions indicate such loss may be avoided. However, few empirical data from multicellular model systems are available, especially regarding variance/covariance (V/CV) relationships. Here, we compare the V/CV structure of seventeen traits related to body size and composition between control (60 mating pairs/generation) and bottlenecked (2 mating pairs/generation; average F = 0.39) strains of mice. Although results for individual traits vary considerably, multivariate analysis indicates that V(a) in the bottlenecked populations is greater than expected. Traits with patterns and amounts of epistasis predictive of enhanced V(a) also show the largest deviations from additive expectations. Finally, the correlation structure of weekly weights is not significantly different between control and experimental lines but correlations between necropsy traits do differ, especially those involving the heart, kidney and tail length.}, } @article {pmid21708975, year = {2011}, author = {Oda, H and Takeichi, M}, title = {Evolution: structural and functional diversity of cadherin at the adherens junction.}, journal = {The Journal of cell biology}, volume = {193}, number = {7}, pages = {1137-1146}, pmid = {21708975}, issn = {1540-8140}, mesh = {Adherens Junctions/*metabolism ; Animals ; Cadherins/chemistry/*physiology ; Cell Adhesion/*physiology ; Drosophila/embryology/metabolism ; Drosophila Proteins/chemistry/physiology ; Embryo, Nonmammalian/metabolism ; *Evolution, Molecular ; Mice ; Protein Structure, Tertiary ; Structure-Activity Relationship ; }, abstract = {Adhesion between cells is essential to the evolution of multicellularity. Indeed, morphogenesis in animals requires firm but flexible intercellular adhesions that are mediated by subcellular structures like the adherens junction (AJ). A key component of AJs is classical cadherins, a group of transmembrane proteins that maintain dynamic cell-cell associations in many animal species. An evolutionary reconstruction of cadherin structure and function provides a comprehensive framework with which to appreciate the diversity of morphogenetic mechanisms in animals.}, } @article {pmid21699890, year = {2011}, author = {Dayel, MJ and Alegado, RA and Fairclough, SR and Levin, TC and Nichols, SA and McDonald, K and King, N}, title = {Cell differentiation and morphogenesis in the colony-forming choanoflagellate Salpingoeca rosetta.}, journal = {Developmental biology}, volume = {357}, number = {1}, pages = {73-82}, pmid = {21699890}, issn = {1095-564X}, support = {T32HG00047/HG/NHGRI NIH HHS/United States ; R01 GM089977-01/GM/NIGMS NIH HHS/United States ; F32 GM086054/GM/NIGMS NIH HHS/United States ; R01 GM089977/GM/NIGMS NIH HHS/United States ; GM089977/GM/NIGMS NIH HHS/United States ; T32 HG000047/HG/NHGRI NIH HHS/United States ; R01 GM089977-03/GM/NIGMS NIH HHS/United States ; R01 GM089977-02/GM/NIGMS NIH HHS/United States ; 5F32GM086054/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Cell Differentiation ; Choanoflagellata/*cytology/metabolism/ultrastructure ; Microscopy, Electron, Scanning ; *Morphogenesis ; Receptors, Cell Surface/metabolism ; }, abstract = {It has been posited that animal development evolved from pre-existing mechanisms for regulating cell differentiation in the single celled and colonial ancestors of animals. Although the progenitors of animals cannot be studied directly, insights into their cell biology may be gleaned from comparisons between animals and their closest living relatives, the choanoflagellates. We report here on the life history, cell differentiation and intercellular interactions in the colony-forming choanoflagellate Salpingoeca rosetta. In response to diverse environmental cues, S. rosetta differentiates into at least five distinct cell types, including three solitary cell types (slow swimmers, fast swimmers, and thecate cells) and two colonial forms (rosettes and chains). Electron microscopy reveals that cells within colonies are held together by a combination of fine intercellular bridges, a shared extracellular matrix, and filopodia. In addition, we have discovered that the carbohydrate-binding protein wheat germ agglutinin specifically stains colonies and the slow swimmers from which they form, showing that molecular differentiation precedes multicellular development. Together, these results help establish S. rosetta as a model system for studying simple multicellularity in choanoflagellates and provide an experimental framework for investigating the origin of animal multicellularity and development.}, } @article {pmid21690338, year = {2011}, author = {Strassmann, JE and Queller, DC}, title = {Evolution of cooperation and control of cheating in a social microbe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {108 Suppl 2}, number = {Suppl 2}, pages = {10855-10862}, pmid = {21690338}, issn = {1091-6490}, mesh = {*Biological Evolution ; Chimera/genetics ; Dictyostelium/*genetics ; Ecology ; Genome, Protozoan ; Reproduction/genetics ; }, abstract = {Much of what we know about the evolution of altruism comes from animals. Here, we show that studying a microbe has yielded unique insights, particularly in understanding how social cheaters are controlled. The social stage of Dictylostelium discoideum occurs when the amoebae run out of their bacterial prey and aggregate into a multicellular, motile slug. This slug forms a fruiting body in which about a fifth of cells die to form a stalk that supports the remaining cells as they form hardy dispersal-ready spores. Because this social stage forms from aggregation, it is analogous to a social group, or a chimeric multicellular organism, and is vulnerable to internal conflict. Advances in cell labeling, microscopy, single-gene knockouts, and genomics, as well as the results of decades of study of D. discoideum as a model for development, allow us to explore the genetic basis of social contests and control of cheaters in unprecedented detail. Cheaters are limited from exploiting other clones by high relatedness, kin discrimination, pleiotropy, noble resistance, and lottery-like role assignment. The active nature of these limits is reflected in the elevated rates of change in social genes compared with nonsocial genes. Despite control of cheaters, some conflict is still expressed in chimeras, with slower movement of slugs, slightly decreased investment in stalk compared with spore cells, and differential contributions to stalk and spores. D. discoideum is rapidly becoming a model system of choice for molecular studies of social evolution.}, } @article {pmid21685384, year = {2011}, author = {Havrylenko, S and Legouis, R and Negrutskii, B and Mirande, M}, title = {Caenorhabditis elegans evolves a new architecture for the multi-aminoacyl-tRNA synthetase complex.}, journal = {The Journal of biological chemistry}, volume = {286}, number = {32}, pages = {28476-28487}, pmid = {21685384}, issn = {1083-351X}, mesh = {Amino Acyl-tRNA Synthetases/genetics/*metabolism ; Animals ; Caenorhabditis elegans/*enzymology/genetics ; Caenorhabditis elegans Proteins/genetics/*metabolism ; *Evolution, Molecular ; Multienzyme Complexes/genetics/*metabolism ; Proteomics ; }, abstract = {MARS is an evolutionary conserved supramolecular assembly of aminoacyl-tRNA synthetases found in eukaryotes. This complex was thought to be ubiquitous in the deuterostome and protostome clades of bilaterians because similar complexes were isolated from arthropods and vertebrates. However, several features of the component enzymes suggested that in the nematode Caenorhabditis elegans, a species grouped with arthropods in modern phylogeny, this complex might not exist, or should display a significantly different structural organization. C. elegans was also taken as a model system to study in a multicellular organism amenable to experimental approaches, the reason for existence of these supramolecular entities. Here, using a proteomic approach, we have characterized the components of MARS in C. elegans. We show that this organism evolved a specific structural organization of this complex, which contains several bona fide components of the MARS complexes known so far, but also displays significant variations. These data highlight molecular evolution events that took place after radiation of bilaterians. Remarkably, it shows that expansion of MARS assembly in metazoans is not linear, but is the result of additions but also of subtractions along evolution. We then undertook an experimental approach, using inactivation of the endogenous copy of methionyl-tRNA synthetase by RNAi and expression of transgenic variants, to understand the role in complex assembly and the in vivo functionality, of the eukaryotic-specific domains appended to aminoacyl-tRNA synthetases. We show that rescue of the worms and assembly of transgenic variants into MARS rest on the presence of these appended domains.}, } @article {pmid21682642, year = {2011}, author = {Strassmann, JE and Gilbert, OM and Queller, DC}, title = {Kin discrimination and cooperation in microbes.}, journal = {Annual review of microbiology}, volume = {65}, number = {}, pages = {349-367}, doi = {10.1146/annurev.micro.112408.134109}, pmid = {21682642}, issn = {1545-3251}, mesh = {Animals ; Bacteria/*genetics ; Bacterial Physiological Phenomena ; Cell Communication ; Eukaryota/genetics/physiology ; *Evolution, Molecular ; Fungi/*genetics/physiology ; Models, Genetic ; *Selection, Genetic ; }, abstract = {Recognition of relatives is important in microbes because they perform many behaviors that have costs to the actor while benefiting neighbors. Microbes cooperate for nourishment, movement, virulence, iron acquisition, protection, quorum sensing, and production of multicellular biofilms or fruiting bodies. Helping others is evolutionarily favored if it benefits others who share genes for helping, as specified by kin selection theory. If microbes generally find themselves in clonal patches, then no special means of discrimination is necessary. Much real discrimination is actually of kinds, not kin, as in poison-antidote systems, such as bacteriocins, in which cells benefit their own kind by poisoning others, and in adhesion systems, in which cells of the same kind bind together. These behaviors can elevate kinship generally and make cooperation easier to evolve and maintain.}, } @article {pmid21680607, year = {2011}, author = {Aki, S and Nakai, H and Aoyama, T and Oka, A and Tsuge, T}, title = {AtSAP130/AtSF3b-3 function is required for reproduction in Arabidopsis thaliana.}, journal = {Plant & cell physiology}, volume = {52}, number = {8}, pages = {1330-1339}, doi = {10.1093/pcp/pcr077}, pmid = {21680607}, issn = {1471-9053}, mesh = {Arabidopsis/cytology/genetics/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; Carrier Proteins/genetics/*metabolism ; Crosses, Genetic ; Gene Duplication/genetics ; Gene Expression Regulation, Plant ; Gene Knockdown Techniques ; Genome, Plant/genetics ; Germination ; Mutation/genetics ; Phenotype ; Phylogeny ; Pollen/cytology/genetics/growth & development ; RNA Interference ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins ; Reproduction/physiology ; }, abstract = {Flowering plants produce multicellular gametophytes through an elaborate regulation of gametogenesis. During female and male gametogenesis in Arabidopsis thaliana, sporogenous cells differentiate and undergo meiosis to produce megaspores and microspores, which in turn go through mitosis to develop into multicellular gametophytes. Here we report that the Arabidopsis spliceosomal protein, SPLICEOSOME-ASSOCIATED PROTEIN 130 (AtSAP130), is required for proper reproduction. AtSAP130 is encoded by two genes, AtSAP130a and AtSAP130b. Plants with reduced expression of the AtSAP130 genes, induced by RNA interference, showed a defect in fertilization. Besides functional impairment observed in the female reproductive organs, analysis focusing on pollen development revealed defects in the transition from the microspore to the bicellular stage. Our results suggest that AtSAP130a and AtSAP130b play an indispensable role in specific spatiotemporal events in reproduction.}, } @article {pmid21674567, year = {2011}, author = {Tucker, T and Riccardi, VM and Brown, C and Fee, J and Sutcliffe, M and Vielkind, J and Wechsler, J and Wolkenstein, P and Friedman, JM}, title = {S100B and neurofibromin immunostaining and X-inactivation patterns of laser-microdissected cells indicate a multicellular origin of some NF1-associated neurofibromas.}, journal = {Journal of neuroscience research}, volume = {89}, number = {9}, pages = {1451-1460}, doi = {10.1002/jnr.22654}, pmid = {21674567}, issn = {1097-4547}, mesh = {Chromosomes, Human, X ; Clone Cells ; Female ; Humans ; Immunohistochemistry ; Microdissection ; Nerve Growth Factors/*metabolism ; Neurofibroma/*metabolism/pathology ; Neurofibromatosis 1/genetics/metabolism/*pathology ; Neurofibromin 1/*metabolism ; Polymorphism, Genetic ; Receptors, Androgen/genetics ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins/*metabolism ; Schwann Cells/classification/*metabolism/pathology ; X Chromosome Inactivation ; }, abstract = {Neurofibromatosis 1 (NF1) is an autosomal dominant disease that predisposes individuals to developing benign neurofibromas. Some features and consequences of NF1 appear to result from partial deficiency of neurofibromin (Nfn), the NF1 gene protein product, as a result of haploinsufficiency for the NF1 gene. Other features and consequences of NF1 appear to involve total deficiency of Nfn, which arises as a result of either loss of function of the second NF1 allele or excess degradation of Nfn produced by the second allele in a particular clone of cells. We used immunofluorescence to assess the presence of Nfn in putative Schwann cells (S100B(+)) and non-Schwann cells (S100B(-)) in 36 NF1-derived benign neurofibromas classified histologically as diffuse or encapsulated. The S100B(+) /Nfn(-) cell population made up only 18% ± 10% (mean ± standard deviation) of the neurofibroma cells in both the diffuse and encapsulated neurofibromas. The proportion of S100B(+) /Nfn(+) cells was significantly higher and the proportion of S100B(-) /Nfn(-) cells was significantly lower in diffuse neurofibromas than in encapsulated neurofibromas. We isolated S100B(+) /Nfn(+) , S100B(+) /Nfn(-) , and S100B(-) /Nfn(+) cells by laser microdissection and, using X-chromosome inactivation profiles, assessed clonality for each cell type. We showed that, although some neurofibromas include a subpopulation of S100B(+) /Nfn(-) cells consistent with clonal expansion of a Schwann cell progenitor that has lost function of both NF1 alleles, other neurofibromas do not show evidence of monoclonal proliferation of Schwann cells. Our findings suggest that, although clonal loss of neurofibromin function is probably involved in the development of some NF1-associated neurofibromas, other pathogenic processes also occur.}, } @article {pmid21664270, year = {2011}, author = {Wagner, BA and Venkataraman, S and Buettner, GR}, title = {The rate of oxygen utilization by cells.}, journal = {Free radical biology & medicine}, volume = {51}, number = {3}, pages = {700-712}, pmid = {21664270}, issn = {1873-4596}, support = {P42 ES007380-05/ES/NIEHS NIH HHS/United States ; P30 CA086862/CA/NCI NIH HHS/United States ; R01 GM073929-02/GM/NIGMS NIH HHS/United States ; P30 CA086862-05/CA/NCI NIH HHS/United States ; P42 ES013661/ES/NIEHS NIH HHS/United States ; R01 GM073929/GM/NIGMS NIH HHS/United States ; P42 ES007380/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Cell Culture Techniques ; Cell Growth Processes ; Cell Size ; Electrophysiology/methods ; *Energy Metabolism ; Humans ; Neoplasms/*metabolism/pathology ; Oxidation-Reduction ; *Oxygen Consumption/physiology ; Protein Biosynthesis ; Reactive Oxygen Species/metabolism ; Reference Values ; U937 Cells ; }, abstract = {The discovery of oxygen is considered by some to be the most important scientific discovery of all time--from both physical-chemical/astrophysics and biology/evolution viewpoints. One of the major developments during evolution is the ability to capture dioxygen in the environment and deliver it to each cell in the multicellular, complex mammalian body-on demand, i.e., just in time. Humans use oxygen to extract approximately 2550 calories (10.4 MJ) from food to meet daily energy requirements. This combustion requires about 22 mol of dioxygen per day, or 2.5×10(-4) mol s(-1). This is an average rate of oxygen utilization of 2.5×10(-18) mol cell(-1) s(-1), i.e., 2.5 amol cell(-1) s(-1). Cells have a wide range of oxygen utilization, depending on cell type, function, and biological status. Measured rates of oxygen utilization by mammalian cells in culture range from <1 to >350 amol cell(-1) s(-1). There is a loose positive linear correlation of the rate of oxygen consumption by mammalian cells in culture with cell volume and cell protein. The use of oxygen by cells and tissues is an essential aspect of the basic redox biology of cells and tissues. This type of quantitative information is fundamental to investigations in quantitative redox biology, especially redox systems biology.}, } @article {pmid21654083, year = {2011}, author = {Reddy, PC and Bidaye, SS and Ghaskadbi, S}, title = {Genome-wide screening reveals the emergence and divergence of RTK homologues in basal Metazoan Hydra magnipapillata.}, journal = {Journal of biosciences}, volume = {36}, number = {2}, pages = {289-296}, pmid = {21654083}, issn = {0973-7138}, mesh = {Animals ; Data Mining ; *Evolution, Molecular ; *Genetic Speciation ; *Genome ; Hydra/*genetics ; Markov Chains ; Models, Genetic ; Phylogeny ; Receptor Protein-Tyrosine Kinases/classification/*genetics ; *Sequence Homology, Amino Acid ; }, abstract = {Receptor tyrosine kinases (RTKs) are key components of cell-cell signalling required for growth and development of multicellular organisms. It is therefore likely that the divergence of RTKs and associated components played a significant role in the evolution of multicellular organisms. We have carried out the present study in hydra, a diploblast, to investigate the divergence of RTKs after parazoa and before emergence of triploblast phyla. The domain-based screening using Hidden Markov Models (HMMs) for RTKs in Genomescan predicted gene models of the Hydra magnipapillata genome resulted in identification of 15 RTKs. These RTKs have been classified into eight families based on domain architecture and homology. Only 5 of these RTKs have been previously reported and a few of these have been partially characterized. A phylogeny-based analysis of these predicted RTKs revealed that seven subtype duplications occurred between 'parazoan-eumetazoan split' and 'diploblast-triploblast split' in animal phyla. These results suggest that most of the RTKs evolved before the radiata-bilateria divergence during animal evolution.}, } @article {pmid21640952, year = {2011}, author = {Boeuf, G}, title = {Marine biodiversity characteristics.}, journal = {Comptes rendus biologies}, volume = {334}, number = {5-6}, pages = {435-440}, doi = {10.1016/j.crvi.2011.02.009}, pmid = {21640952}, issn = {1768-3238}, mesh = {Animals ; *Biodiversity ; Biological Evolution ; Earth, Planet ; Ecosystem ; Humans ; *Marine Biology ; Models, Biological ; Oceans and Seas ; }, abstract = {Oceans contain the largest living volume of the "blue" planet, inhabited by approximately 235-250,000 described species, all groups included. They only represent some 13% of the known species on the Earth, but the marine biomasses are really huge. Marine phytoplankton alone represents half the production of organic matter on Earth while marine bacteria represent more than 10%. Life first appeared in the oceans more than 3.8 billion years ago and several determining events took place that changed the course of life, ranging from the development of the cell nucleus to sexual reproduction going through multi-cellular organisms and the capture of organelles. Of the 31 animal phyla currently listed, 12 are exclusively marine phyla and have never left the ocean. An interesting question is to try to understand why there are so few marine species versus land species? This pattern of distribution seems pretty recent in the course of Evolution. From an exclusively marine world, since the beginning until 440 million years ago, land number of species much increased 110 million years ago. Specific diversity and ancestral roles, in addition to organizational models and original behaviors, have made marine organisms excellent reservoirs for identifying and extracting molecules (>15,000 today) with pharmacological potential. They also make particularly relevant models for both fundamental and applied research. Some marine models have been the source of essential discoveries in life sciences. From this diversity, the ocean provides humankind with renewable resources, which are highly threatened today and need more adequate management to preserve ocean habitats, stocks and biodiversity.}, } @article {pmid21638001, year = {2011}, author = {Yang, C and Li, H and Zhang, J and Wang, T and Ye, Z}, title = {Fine-mapping of the woolly gene controlling multicellular trichome formation and embryonic development in tomato.}, journal = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik}, volume = {123}, number = {4}, pages = {625-633}, pmid = {21638001}, issn = {1432-2242}, mesh = {*Chromosome Mapping ; Chromosome Segregation ; Chromosomes, Artificial, Bacterial/genetics ; DNA, Plant/genetics ; Genes, Plant ; Genetic Markers ; Solanum lycopersicum/*genetics/*growth & development ; Microsatellite Repeats ; Open Reading Frames ; Plant Proteins/genetics/metabolism ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {Trichomes are small hairs that originate from the epidermal cells of nearly all land plants, and they exist in unicellular and multicellular forms. The regulatory pathway of unicellular trichomes in Arabidopsis is well characterized. However, little is known about the multicellular trichome formation in tomato (Solanum lycopersicum). The woolly (Wo) gene controls multicellular trichome initiation and leads to embryonic lethality when homozygous in tomato. To clone and characterize Wo, the gene was fine-mapped to a DNA fragment of ~200 kb using the map-based cloning strategy. A series of sequence-based molecular markers, including simple sequence repeat, sequence characterized amplified region, and cleaved amplified polymorphic sequence were utilized in this study. Analysis of the sequence indicated that this region carries 19 putative open reading frames. These results will provide not only the important information for the isolation and characterization of Wo but also the starting point for studying the regulatory pathway responsible for trichome formation and embryonic lethality in tomato.}, } @article {pmid21632547, year = {2011}, author = {Yoshiyama-Yanagawa, T and Enya, S and Shimada-Niwa, Y and Yaguchi, S and Haramoto, Y and Matsuya, T and Shiomi, K and Sasakura, Y and Takahashi, S and Asashima, M and Kataoka, H and Niwa, R}, title = {The conserved Rieske oxygenase DAF-36/Neverland is a novel cholesterol-metabolizing enzyme.}, journal = {The Journal of biological chemistry}, volume = {286}, number = {29}, pages = {25756-25762}, pmid = {21632547}, issn = {1083-351X}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Caenorhabditis elegans/cytology/enzymology/genetics ; Cell Line ; Cholesterol/*metabolism ; *Conserved Sequence ; Dehydrocholesterols/metabolism ; Drosophila melanogaster/cytology/enzymology/genetics/growth & development ; Evolution, Molecular ; Microsomes/metabolism ; Molecular Sequence Data ; Oxygenases/*chemistry/genetics/*metabolism ; Protein Transport ; Sequence Homology, Nucleic Acid ; Species Specificity ; }, abstract = {Steroid hormones play essential roles in a wide variety of biological processes in multicellular organisms. The principal steroid hormones in nematodes and arthropods are dafachronic acids and ecdysteroids, respectively, both of which are synthesized from cholesterol as an indispensable precursor. The first critical catalytic step in the biosynthesis of these ecdysozoan steroids is the conversion of cholesterol to 7-dehydrocholesterol. However, the enzymes responsible for cholesterol 7,8-dehydrogenation remain unclear at the molecular level. Here we report that the Rieske oxygenase DAF-36/Neverland (Nvd) is a cholesterol 7,8-dehydrogenase. The daf-36/nvd genes are evolutionarily conserved, not only in nematodes and insects but also in deuterostome species that do not produce dafachronic acids or ecdysteroids, including the sea urchin Hemicentrotus pulcherrimus, the sea squirt Ciona intestinalis, the fish Danio rerio, and the frog Xenopus laevis. An in vitro enzymatic assay system reveals that all DAF-36/Nvd proteins cloned so far have the ability to convert cholesterol to 7-dehydrocholesterol. Moreover, the lethality of loss of nvd function in the fruit fly Drosophila melanogaster is rescued by the expression of daf-36/nvd genes from the nematode Caenorhabditis elegans, the insect Bombyx mori, or the vertebrates D. rerio and X. laevis. These data suggest that daf-36/nvd genes are functionally orthologous across the bilaterian phylogeny. We propose that the daf-36/nvd family of proteins is a novel conserved player in cholesterol metabolism across the animal phyla.}, } @article {pmid21621938, year = {2011}, author = {Grégoire, P and Fardeau, ML and Joseph, M and Guasco, S and Hamaide, F and Biasutti, S and Michotey, V and Bonin, P and Ollivier, B}, title = {Isolation and characterization of Thermanaerothrix daxensis gen. nov., sp. nov., a thermophilic anaerobic bacterium pertaining to the phylum "Chloroflexi", isolated from a deep hot aquifer in the Aquitaine Basin.}, journal = {Systematic and applied microbiology}, volume = {34}, number = {7}, pages = {494-497}, doi = {10.1016/j.syapm.2011.02.004}, pmid = {21621938}, issn = {1618-0984}, mesh = {Acetates/metabolism ; Bacterial Typing Techniques ; Base Composition ; Base Sequence ; Carbohydrate Metabolism ; Cell Wall/metabolism ; Chloroflexi/*classification/genetics/growth & development/*isolation & purification/metabolism ; Fermentation ; France ; Genes, Bacterial ; Genes, rRNA ; Glucose/metabolism ; Gram-Negative Anaerobic Bacteria/*classification/genetics/growth & development/*isolation & purification/metabolism ; Hot Springs/*microbiology ; Hot Temperature ; Hydrogen/metabolism ; Hydrogen-Ion Concentration ; Lactic Acid/metabolism ; Microscopy, Phase-Contrast ; Molecular Sequence Data ; Phenotype ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Water Microbiology ; }, abstract = {A new strictly anaerobic thermophilic multicellular filamentous bacterium (0.2-0.3μm×>100μm), designated GNS-1(T), was isolated from a deep hot aquifer in France. It was non-motile, and stained Gram-negative. Optimal growth was observed at 65°C, pH 7.0, and 2gL(-1) of NaCl. Strain GNS-1(T) was chemoorganotrophic fermenting ribose, glucose, galactose, arabinose, fructose, mannose, maltose, sucrose, xylose, raffinose, pyruvate, and xylan. Yeast extract was required for growth. The end products of glucose fermentation were lactate, acetate, CO(2), and H(2). The G+C content of the DNA was 57.6mol%. Its closest phylogenetic relative was Bellilinea caldifistulae with 92.5% similarity. Based on phylogenetic, genotypic and phenotypic characteristics, strain GNS-1(T) (DSM 23592(T), JCM 16980(T)) is proposed to be assigned to a novel species of a novel genus within the class Anaerolineae (subphylum I), phylum "Chloroflexi", Thermanaerothrix daxensis gen. nov., sp. nov. The GenBank accession number is HM596746.}, } @article {pmid21604113, year = {2011}, author = {Gouw, JW and Tops, BB and Krijgsveld, J}, title = {Metabolic labeling of model organisms using heavy nitrogen (15N).}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {753}, number = {}, pages = {29-42}, doi = {10.1007/978-1-61779-148-2_2}, pmid = {21604113}, issn = {1940-6029}, mesh = {Animals ; Caenorhabditis elegans/chemistry/metabolism ; Drosophila melanogaster/chemistry/metabolism ; Escherichia coli/chemistry/metabolism ; Female ; Isotope Labeling/*methods ; Male ; Mass Spectrometry/methods ; Nitrogen/*chemistry ; Peptides/chemistry ; Proteins/*chemistry/*metabolism ; Proteomics/*methods ; Saccharomyces cerevisiae/chemistry/metabolism ; }, abstract = {Quantitative proteomics aims to identify and quantify proteins in cells or organisms that have been obtained from different biological origin (e.g., "healthy vs. diseased"), that have received different treatments, or that have different genetic backgrounds. Protein expression levels can be quantified by labeling proteins with stable isotopes, followed by mass spectrometric analysis. Stable isotopes can be introduced in vitro by reacting proteins or peptides with isotope-coded reagents (e.g., iTRAQ, reductive methylation). A preferred way, however, is the metabolic incorporation of heavy isotopes into cells or organisms by providing the label, in the form of amino acids (such as in SILAC) or salts, in the growth media. The advantage of in vivo labeling is that it does not suffer from side reactions or incomplete labeling that might occur in chemical derivatization. In addition, metabolic labeling occurs at the earliest possible moment in the sample preparation process, thereby minimizing the error in quantitation. Labeling with the heavy stable isotope of nitrogen (i.e., (15)N) provides an efficient way for accurate protein quantitation. Where the application of SILAC is mostly restricted to cell culture, (15)N labeling can be used for micro-organisms as well as a number of higher (multicellular) organisms. The most prominent examples of the latter are Caenorhabditis elegans and Drosophila (fruit fly), two important model organisms for a range of regulatory processes underlying developmental biology. Here we describe in detail the labeling with (15)N atoms, with a particular focus on fruit flies and C. elegans. We also describe methods for the identification and quantitation of (15)N-labeled proteins by mass spectrometry and bioinformatic analysis.}, } @article {pmid21601638, year = {2011}, author = {Douglas, TE and Kronforst, MR and Queller, DC and Strassmann, JE}, title = {Genetic diversity in the social amoeba Dictyostelium discoideum: population differentiation and cryptic species.}, journal = {Molecular phylogenetics and evolution}, volume = {60}, number = {3}, pages = {455-462}, doi = {10.1016/j.ympev.2011.05.007}, pmid = {21601638}, issn = {1095-9513}, mesh = {Bayes Theorem ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; DNA, Ribosomal/genetics ; Dictyostelium/classification/*genetics ; *Evolution, Molecular ; *Genetic Speciation ; *Genetic Variation ; Genetics, Population ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {The social amoeba Dictyostelium discoideum is a commonly used model organism for the study of social evolution, multicellularity, and cell biology. But the boundaries and structure of the species have not been explored. The lack of morphological traits to distinguish D. discoideum makes even knowing whether a given clone is D. discoideum a challenge. We address this with a phylogeny of a widespread collection of clones from a range of locations and including clones identified previously as potential cryptic species. We sequenced portions of nuclear ribosomal DNA and mitochondrial DNA, analyzing approximately 5500 and 2500 base pairs from the two regions respectively. We compared these sequences to known reference sequences for both D. discoideum and other closely related Dictyostelium species to create Bayesian and neighbor-joining phylogenetic trees representing the evolutionary relationships among the clones. We identified 51 unique D. discoideum concatenated sequences based on the combined mitochondrial and ribosomal sequence data. We also identified four unique D. citrinum concatenated sequences, three of which were previously classified as D. discoideum clones. Our analysis of the data revealed that all D. discoideum clones form a monophyletic group, but there are several well-supported subclades and pronounced genetic differentiation among locations (F(ST)=0.242, P=0.011), suggesting the presence of geographic or other barriers between populations. Our results reveal the need for further investigation into potential tropical cryptic species.}, } @article {pmid21593871, year = {2011}, author = {Roppolo, D and De Rybel, B and Dénervaud Tendon, V and Pfister, A and Alassimone, J and Vermeer, JE and Yamazaki, M and Stierhof, YD and Beeckman, T and Geldner, N}, title = {A novel protein family mediates Casparian strip formation in the endodermis.}, journal = {Nature}, volume = {473}, number = {7347}, pages = {380-383}, pmid = {21593871}, issn = {1476-4687}, mesh = {Arabidopsis/*cytology/*metabolism/ultrastructure ; Arabidopsis Proteins/genetics/*metabolism/ultrastructure ; Biopolymers/chemistry/metabolism ; Cell Membrane/*metabolism ; Diffusion ; Extracellular Space/metabolism ; Hydrophobic and Hydrophilic Interactions ; Membrane Proteins/genetics/*metabolism/ultrastructure ; Molecular Sequence Data ; Multigene Family ; Plant Roots/*cytology/*metabolism ; Protein Binding ; }, abstract = {Polarized epithelia are fundamental to multicellular life. In animal epithelia, conserved junctional complexes establish membrane diffusion barriers, cellular adherence and sealing of the extracellular space. Plant cellular barriers are of independent evolutionary origin. The root endodermis strongly resembles a polarized epithelium and functions in nutrient uptake and stress resistance. Its defining features are the Casparian strips, belts of specialized cell wall material that generate an extracellular diffusion barrier. The mechanisms localizing Casparian strips are unknown. Here we identify and characterize a family of transmembrane proteins of previously unknown function. These 'CASPs' (Casparian strip membrane domain proteins) specifically mark a membrane domain that predicts the formation of Casparian strips. CASP1 displays numerous features required for a constituent of a plant junctional complex: it forms complexes with other CASPs; it becomes immobile upon localization; and it sediments like a large polymer. CASP double mutants display disorganized Casparian strips, demonstrating a role for CASPs in structuring and localizing this cell wall modification. To our knowledge, CASPs are the first molecular factors that are shown to establish a plasma membrane and extracellular diffusion barrier in plants, and represent a novel way of epithelial barrier formation in eukaryotes.}, } @article {pmid21593762, year = {2011}, author = {Fernández, A and Lynch, M}, title = {Non-adaptive origins of interactome complexity.}, journal = {Nature}, volume = {474}, number = {7352}, pages = {502-505}, pmid = {21593762}, issn = {1476-4687}, support = {R01GM072614/GM/NIGMS NIH HHS/United States ; R01 GM036827-17S1/GM/NIGMS NIH HHS/United States ; R01GM036827/GM/NIGMS NIH HHS/United States ; R01 GM036827/GM/NIGMS NIH HHS/United States ; R01 GM072614/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; Caenorhabditis elegans ; Computational Biology ; Escherichia coli ; *Evolution, Molecular ; *Genetic Drift ; Hemoglobins/chemistry/metabolism ; Humans ; Hydrogen Bonding ; Metabolic Networks and Pathways/genetics/*physiology ; Models, Genetic ; Models, Molecular ; Phenotype ; Phylogeny ; Population Density ; Protein Binding ; Protein Conformation ; Proteins/chemistry/genetics/*metabolism ; Selection, Genetic ; Solubility ; Species Specificity ; Superoxide Dismutase/chemistry/metabolism ; Water/chemistry ; }, abstract = {The boundaries between prokaryotes, unicellular eukaryotes and multicellular eukaryotes are accompanied by orders-of-magnitude reductions in effective population size, with concurrent amplifications of the effects of random genetic drift and mutation. The resultant decline in the efficiency of selection seems to be sufficient to influence a wide range of attributes at the genomic level in a non-adaptive manner. A key remaining question concerns the extent to which variation in the power of random genetic drift is capable of influencing phylogenetic diversity at the subcellular and cellular levels. Should this be the case, population size would have to be considered as a potential determinant of the mechanistic pathways underlying long-term phenotypic evolution. Here we demonstrate a phylogenetically broad inverse relation between the power of drift and the structural integrity of protein subunits. This leads to the hypothesis that the accumulation of mildly deleterious mutations in populations of small size induces secondary selection for protein-protein interactions that stabilize key gene functions. By this means, the complex protein architectures and interactions essential to the genesis of phenotypic diversity may initially emerge by non-adaptive mechanisms.}, } @article {pmid21593029, year = {2011}, author = {Rossetti, V and Filippini, M and Svercel, M and Barbour, AD and Bagheri, HC}, title = {Emergent multicellular life cycles in filamentous bacteria owing to density-dependent population dynamics.}, journal = {Journal of the Royal Society, Interface}, volume = {8}, number = {65}, pages = {1772-1784}, pmid = {21593029}, issn = {1742-5662}, mesh = {Algorithms ; Bacterial Physiological Phenomena ; Bacteroidetes/metabolism/*physiology ; Computer Simulation ; Cyanobacteria/metabolism/*physiology ; Models, Biological ; Models, Statistical ; Models, Theoretical ; Photochemistry/methods ; Population Dynamics ; Species Specificity ; Time Factors ; }, abstract = {Filamentous bacteria are the oldest and simplest known multicellular life forms. By using computer simulations and experiments that address cell division in a filamentous context, we investigate some of the ecological factors that can lead to the emergence of a multicellular life cycle in filamentous life forms. The model predicts that if cell division and death rates are dependent on the density of cells in a population, a predictable cycle between short and long filament lengths is produced. During exponential growth, there will be a predominance of multicellular filaments, while at carrying capacity, the population converges to a predominance of short filaments and single cells. Model predictions are experimentally tested and confirmed in cultures of heterotrophic and phototrophic bacterial species. Furthermore, by developing a formulation of generation time in bacterial populations, it is shown that changes in generation time can alter length distributions. The theory predicts that given the same population growth curve and fitness, species with longer generation times have longer filaments during comparable population growth phases. Characterization of the environmental dependence of morphological properties such as length, and the number of cells per filament, helps in understanding the pre-existing conditions for the evolution of developmental cycles in simple multicellular organisms. Moreover, the theoretical prediction that strains with the same fitness can exhibit different lengths at comparable growth phases has important implications. It demonstrates that differences in fitness attributed to morphology are not the sole explanation for the evolution of life cycles dominated by multicellularity.}, } @article {pmid21585362, year = {2011}, author = {Strassmann, JE and Queller, DC}, title = {How social evolution theory impacts our understanding of development in the social amoeba Dictyostelium.}, journal = {Development, growth & differentiation}, volume = {53}, number = {4}, pages = {597-607}, doi = {10.1111/j.1440-169X.2011.01272.x}, pmid = {21585362}, issn = {1440-169X}, mesh = {*Biological Evolution ; Dictyostelium/genetics/*physiology ; Genes, Protozoan ; Selection, Genetic ; }, abstract = {Dictyostelium discoideum has been very useful for elucidating principles of development over the last 50 years, but a key attribute means there is a lot to be learned from a very different intellectual tradition: social evolution. Because Dictyostelium arrives at multicellularity by aggregation instead of through a single-cell bottleneck, the multicellular body could be made up of genetically distinct cells. If they are genetically distinct, natural selection will result in conflict over which cells become fertile spores and which become dead stalk cells. Evidence for this conflict includes unequal representation of two genetically different clones in spores of a chimera, the poison-like differentiation inducing factor (DIF) system that appears to involve some cells forcing others to become stalk, and reduced functionality in migrating chimeras. Understanding how selection operates on chimeras of genetically distinct clones is crucial for a comprehensive view of Dictyostelium multicellularity. In nature, Dictyostelium fruiting bodies are often clonal, or nearly so, meaning development will often be very cooperative. Relatedness levels tell us what benefits must be present for sociality to evolve. Therefore it is important to measure relatedness in nature, show that it has an impact on cooperation in the laboratory, and investigate genes that Dictyostelium uses to discriminate between relatives and non-relatives. Clearly, there is a promising future for research at the interface of development and social evolution in this fascinating group.}, } @article {pmid21585352, year = {2011}, author = {Schaap, P}, title = {Evolution of developmental cyclic adenosine monophosphate signaling in the Dictyostelia from an amoebozoan stress response.}, journal = {Development, growth & differentiation}, volume = {53}, number = {4}, pages = {452-462}, pmid = {21585352}, issn = {1440-169X}, support = {//Wellcome Trust/United Kingdom ; 090276//Wellcome Trust/United Kingdom ; BB/G020426/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; WT090276MA/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Cyclic AMP/*metabolism ; Dictyostelium/*metabolism ; *Signal Transduction ; }, abstract = {The Dictyostelid social amoebas represent one of nature's several inventions of multicellularity. Though normally feeding as single cells, nutrient stress triggers the collection of amoebas into colonies that form delicately shaped fruiting structures in which the cells differentiate into spores and up to three cell types to support the spore mass. Cyclic adenosine monophosphate (cAMP) plays a very dominant role in controlling morphogenesis and cell differentiation in the model species Dictyostelium discoideum. As a secreted chemoattractant cAMP coordinates cell movement during aggregation and fruiting body morphogenesis. Secreted cAMP also controls gene expression at different developmental stages, while intracellular cAMP is extensively used to transduce the effect of other stimuli that control the developmental program. In this review, I present an overview of the different roles of cAMP in the model D. discoideum and I summarize studies aimed to resolve how these roles emerged during Dictyostelid evolution.}, } @article {pmid21585351, year = {2011}, author = {Urushihara, H}, title = {Social amoeba and the origin of multicellularity.}, journal = {Development, growth & differentiation}, volume = {53}, number = {4}, pages = {451}, doi = {10.1111/j.1440-169X.2011.01262.x}, pmid = {21585351}, issn = {1440-169X}, mesh = {Amoeba/cytology/*physiology ; }, } @article {pmid21571926, year = {2011}, author = {Young, SL and Diolaiti, D and Conacci-Sorrell, M and Ruiz-Trillo, I and Eisenman, RN and King, N}, title = {Premetazoan ancestry of the Myc-Max network.}, journal = {Molecular biology and evolution}, volume = {28}, number = {10}, pages = {2961-2971}, pmid = {21571926}, issn = {1537-1719}, support = {R37 CA057138/CA/NCI NIH HHS/United States ; R37CA57138/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Basic-Leucine Zipper Transcription Factors/chemistry/*genetics/metabolism ; Conserved Sequence ; E-Box Elements ; Evolution, Molecular ; Microscopy, Fluorescence ; Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Placozoa/*genetics ; Proto-Oncogene Proteins c-myc/chemistry/*genetics/metabolism ; Sea Anemones/*genetics ; Sequence Alignment ; Species Specificity ; }, abstract = {The origin of metazoans required the evolution of mechanisms for maintaining differentiated cell types within a multicellular individual, in part through spatially differentiated patterns of gene transcription. The unicellular ancestor of metazoans was presumably capable of regulating gene expression temporally in response to changing environmental conditions, and spatial cell differentiation in metazoans may represent a co-option of preexisting regulatory mechanisms. Myc is a critical regulator of cell growth, proliferation, and death that is found in all metazoans but absent in other multicellular lineages, including fungi and plants. Homologs of Myc and its binding partner, Max, exist in two of the closest living relatives of animals, the choanoflagellate Monosiga brevicollis (Mb) and Capsaspora owczarzaki, a unicellular opisthokont that is closely related to metazoans and choanoflagellates. We find that Myc and Max from M. brevicollis heterodimerize and bind to both canonical and noncanonical E-boxes, the DNA-binding sites through which metazoan Myc proteins act. Moreover, in M. brevicollis, MbMyc protein can be detected in nuclear and flagellar regions. Like metazoan Max proteins, MbMax can form homodimers that bind to E-boxes. However, cross-species dimerization between Mb and human Myc and Max proteins was not observed, suggesting that the binding interface has diverged. Our results reveal that the Myc/Max network arose before the divergence of the choanoflagellate and metazoan lineages. Furthermore, core features of metazoan Myc function, including heterodimerization with Max, binding to E-box sequences in DNA, and localization to the nucleus, predate the origin of metazoans.}, } @article {pmid21566464, year = {2011}, author = {Smirlis, D and Soteriadou, K}, title = {Trypanosomatid apoptosis: 'Apoptosis' without the canonical regulators.}, journal = {Virulence}, volume = {2}, number = {3}, pages = {253-256}, doi = {10.4161/viru.2.3.16278}, pmid = {21566464}, issn = {2150-5608}, mesh = {*Apoptosis ; Leishmania/genetics/metabolism/*physiology ; Trypanosoma/genetics/metabolism/*physiology ; }, abstract = {Apoptosis is a regulated process of cell death originally described in multicelullar organisms contributing to their development and functionality. There is now increasing experimental evidence that a similar form of cell death is operative in unicellular eukaryotes, including trypanosomatids of the genera Trypanosoma and Leishmania. The determination of ancestral executors and regulators of 'apoptosis' in these protozoa belonging to the most primitive eukaryotes that appeared on earth 1.5 billion years ago, provide an exciting challenge in the understanding of the evolution of apoptosis-regulating processes. A review of the present knowledge of trypanosomatid apoptosis points to the fact that these dying protozoa acquire common apoptotic morphological features as metazoan cells, although they lack many of the molecules accepted today as canonical apoptosis mediators (Bcl-2 family members, caspases, TNF related family of receptors). Herein, we discuss how the knowledge of regulators and executors of trypanosomatid apoptosis may provide answers to the gaps concerning the origin of apoptosis. The aim of this addendum is to emphasize the need for classifying the ancestral death program and to discuss how this relates to the complex death programs in multicellular lineages, with the hope to stimulate further enquiry and research into this area.}, } @article {pmid21561969, year = {2012}, author = {Simpson, C}, title = {The evolutionary history of division of labour.}, journal = {Proceedings. Biological sciences}, volume = {279}, number = {1726}, pages = {116-121}, pmid = {21561969}, issn = {1471-2954}, mesh = {Animals ; Behavior, Animal ; *Biological Evolution ; Fossils ; Invertebrates/anatomy & histology/classification/*physiology ; Models, Biological ; Reproduction ; *Social Behavior ; Vertebrates/anatomy & histology/classification/*physiology ; }, abstract = {Functional specialization, or division of labour (DOL), of parts within organisms and colonies is common in most multi-cellular, colonial and social organisms, but it is far from ubiquitous. Several mechanisms have been proposed to explain the evolutionary origins of DOL; the basic feature common to all of them is that functional differences can arise easily. These mechanisms cannot explain the many groups of colonial and social animals that exhibit no DOL despite up to 500 million years of evolution. Here, I propose a new hypothesis, based on a multi-level selection theory, which predicts that a reproductive DOL is required to evolve prior to subsequent functional specialization. I test this hypothesis using a dataset consisting of the type of DOL for living and extinct colonial and social animals. The frequency distribution of DOL and the sequence of its acquisition confirm that reproductive specialization evolves prior to functional specialization. A corollary of this hypothesis is observed in colonial, social and also within multi-cellular organisms; those species without a reproductive DOL have a smaller range of internal variation, in terms of the number of polymorphs or cell types, than species with a reproductive DOL.}, } @article {pmid21558422, year = {2011}, author = {Studer, RA and Person, E and Robinson-Rechavi, M and Rossier, BC}, title = {Evolution of the epithelial sodium channel and the sodium pump as limiting factors of aldosterone action on sodium transport.}, journal = {Physiological genomics}, volume = {43}, number = {13}, pages = {844-854}, doi = {10.1152/physiolgenomics.00002.2011}, pmid = {21558422}, issn = {1531-2267}, mesh = {Acid Sensing Ion Channels ; Aldosterone/*metabolism ; Animals ; Degenerin Sodium Channels ; Epithelial Sodium Channels/*genetics ; *Evolution, Molecular ; Humans ; Ion Transport/drug effects ; Membrane Proteins/genetics ; Nerve Tissue Proteins/genetics ; Phosphoproteins/genetics ; Phylogeny ; Sodium/*metabolism ; Sodium-Potassium-Exchanging ATPase/*genetics ; }, abstract = {Despite large changes in salt intake, the mammalian kidney is able to maintain the extracellular sodium concentration and osmolarity within very narrow margins, thereby controlling blood volume and blood pressure. In the aldosterone-sensitive distal nephron (ASDN), aldosterone tightly controls the activities of epithelial sodium channel (ENaC) and Na,K-ATPase, the two limiting factors in establishing transepithelial sodium transport. It has been proposed that the ENaC/degenerin gene family is restricted to Metazoans, whereas the α- and β-subunits of Na,K-ATPase have homologous genes in prokaryotes. This raises the question of the emergence of osmolarity control. By exploring recent genomic data of diverse organisms, we found that: 1) ENaC/degenerin exists in all of the Metazoans screened, including nonbilaterians and, by extension, was already present in ancestors of Metazoa; 2) ENaC/degenerin is also present in Naegleria gruberi, an eukaryotic microbe, consistent with either a vertical inheritance from the last common ancestor of Eukaryotes or a lateral transfer between Naegleria and Metazoan ancestors; and 3) The Na,K-ATPase β-subunit is restricted to Holozoa, the taxon that includes animals and their closest single-cell relatives. Since the β-subunit of Na,K-ATPase plays a key role in targeting the α-subunit to the plasma membrane and has an additional function in the formation of cell junctions, we propose that the emergence of Na,K-ATPase, together with ENaC/degenerin, is linked to the development of multicellularity in the Metazoan kingdom. The establishment of multicellularity and the associated extracellular compartment ("internal milieu") precedes the emergence of other key elements of the aldosterone signaling pathway.}, } @article {pmid21558384, year = {2011}, author = {Kasili, R and Huang, CC and Walker, JD and Simmons, LA and Zhou, J and Faulk, C and Hülskamp, M and Larkin, JC}, title = {BRANCHLESS TRICHOMES links cell shape and cell cycle control in Arabidopsis trichomes.}, journal = {Development (Cambridge, England)}, volume = {138}, number = {11}, pages = {2379-2388}, pmid = {21558384}, issn = {1477-9129}, support = {P30 ES017885/ES/NIEHS NIH HHS/United States ; R01 ES017524/ES/NIEHS NIH HHS/United States ; T32 ES007062/ES/NIEHS NIH HHS/United States ; }, mesh = {Arabidopsis/*cytology/genetics/growth & development ; Arabidopsis Proteins/*genetics/*metabolism ; *Cell Cycle ; Cell Cycle Proteins/*genetics/*metabolism ; Cell Differentiation ; Cell Shape ; *DNA Replication ; Gene Expression Regulation, Plant ; Morphogenesis ; Mutation ; Nuclear Proteins/*genetics/*metabolism ; Phenotype ; Plant Leaves/cytology ; Ploidies ; Polymerase Chain Reaction ; Signal Transduction ; }, abstract = {Endoreplication, also called endoreduplication, is a modified cell cycle in which DNA is repeatedly replicated without subsequent cell division. Endoreplication is often associated with increased cell size and specialized cell shapes, but the mechanism coordinating DNA content with shape and size remains obscure. Here we identify the product of the BRANCHLESS TRICHOMES (BLT) gene, a protein of hitherto unknown function that has been conserved throughout angiosperm evolution, as a link in coordinating cell shape and nuclear DNA content in endoreplicated Arabidopsis trichomes. Loss-of-function mutations in BLT were found to enhance the multicellular trichome phenotype of mutants in the SIAMESE (SIM) gene, which encodes a repressor of endoreplication. Epistasis and overexpression experiments revealed that BLT encodes a key regulator of trichome branching. Additional experiments showed that BLT interacts both genetically and physically with STICHEL, another key regulator of trichome branching. Although blt mutants have normal trichome DNA content, overexpression of BLT results in an additional round of endoreplication, and blt mutants uncouple DNA content from morphogenesis in mutants with increased trichome branching, further emphasizing its role in linking cell shape and endoreplication.}, } @article {pmid21557469, year = {2011}, author = {Newman, SA}, title = {Animal egg as evolutionary innovation: a solution to the "embryonic hourglass" puzzle.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {316}, number = {7}, pages = {467-483}, doi = {10.1002/jez.b.21417}, pmid = {21557469}, issn = {1552-5015}, mesh = {Adaptation, Physiological/genetics ; Animals ; *Biological Evolution ; Body Patterning/*genetics/physiology ; Embryonic Development/genetics ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Models, Biological ; Ovum/*growth & development ; }, abstract = {The evolutionary origin of the egg stage of animal development presents several difficulties for conventional developmental and evolutionary narratives. If the egg's internal organization represents a template for key features of the developed organism, why can taxa within a given phylum exhibit very different egg types, pass through a common intermediate morphology (the so-called "phylotypic stage"), only to diverge again, thus exemplifying the embryonic "hourglass"? Moreover, if different egg types typically represent adaptations to different environmental conditions, why do birds and mammals, for example, have such vastly different eggs with respect to size, shape, and postfertilization dynamics, whereas all these features are more similar for ascidians and mammals? Here, I consider the possibility that different body plans had their origin in self-organizing physical processes in ancient clusters of cells, and suggest that eggs represented a set of independent evolutionary innovations subsequently inserted into the developmental trajectories of such aggregates. I first describe how "dynamical patterning modules" (DPMs) associations between components of the metazoan developmental-genetic toolkit and certain physical processes and effects may have organized primitive animal body plans independently of an egg stage. Next, I describe how adaptive specialization of cells released from such aggregates could have become "proto-eggs," which regenerated the parental cell clusters by cleavage, conserving the characteristic DPMs available to a lineage. Then, I show how known processes of cytoplasmic reorganization following fertilization are often based on spontaneous, self-organizing physical effects ("egg-patterning processes": EPPs). I suggest that rather than acting as developmental blueprints or prepatterns, the EPPs refine the phylotypic body plans determined by the DPMs by setting the boundary and initial conditions under which these multicellular patterning mechanisms operate. Finally, I describe how this new perspective provides a resolution to the embryonic hourglass puzzle.}, } @article {pmid21556326, year = {2011}, author = {O'Reilly, AJ and Dacks, JB and Field, MC}, title = {Evolution of the karyopherin-β family of nucleocytoplasmic transport factors; ancient origins and continued specialization.}, journal = {PloS one}, volume = {6}, number = {4}, pages = {e19308}, pmid = {21556326}, issn = {1932-6203}, support = {//Wellcome Trust/United Kingdom ; 090007//Wellcome Trust/United Kingdom ; }, mesh = {Cell Nucleus/*metabolism ; Cytoplasm/*metabolism ; *Evolution, Molecular ; Humans ; Phylogeny ; Proteomics ; beta Karyopherins/classification/*genetics ; }, abstract = {BACKGROUND: Macromolecular transport across the nuclear envelope (NE) is achieved through nuclear pore complexes (NPCs) and requires karyopherin-βs (KAP-βs), a family of soluble receptors, for recognition of embedded transport signals within cargo. We recently demonstrated, through proteomic analysis of trypanosomes, that NPC architecture is likely highly conserved across the Eukaryota, which in turn suggests conservation of the transport mechanisms. To determine if KAP-β diversity was similarly established early in eukaryotic evolution or if it was subsequently layered onto a conserved NPC, we chose to identify KAP-β sequences in a diverse range of eukaryotes and to investigate their evolutionary history.

RESULTS: Thirty six predicted proteomes were scanned for candidate KAP-β family members. These resulting sequences were resolved into fifteen KAP-β subfamilies which, due to broad supergroup representation, were most likely represented in the last eukaryotic common ancestor (LECA). Candidate members of each KAP-β subfamily were found in all eukaryotic supergroups, except XPO6, which is absent from Archaeplastida. Phylogenetic reconstruction revealed the likely evolutionary relationships between these different subfamilies. Many species contain more than one representative of each KAP-β subfamily; many duplications are apparently taxon-specific but others result from duplications occurring earlier in eukaryotic history.

CONCLUSIONS: At least fifteen KAP-β subfamilies were established early in eukaryote evolution and likely before the LECA. In addition we identified expansions at multiple stages within eukaryote evolution, including a multicellular plant-specific KAP-β, together with frequent secondary losses. Taken with evidence for early establishment of NPC architecture, these data demonstrate that multiple pathways for nucleocytoplasmic transport were established prior to the radiation of modern eukaryotes but that selective pressure continues to sculpt the KAP-β family.}, } @article {pmid21549958, year = {2011}, author = {Katsir, L and Davies, KA and Bergmann, DC and Laux, T}, title = {Peptide signaling in plant development.}, journal = {Current biology : CB}, volume = {21}, number = {9}, pages = {R356-64}, pmid = {21549958}, issn = {1879-0445}, support = {R01 GM086632/GM/NIGMS NIH HHS/United States ; R01 GM086632-03/GM/NIGMS NIH HHS/United States ; 1R01GM086632-01/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis Proteins/genetics/*physiology ; *Biological Evolution ; Cell Communication/*physiology ; Cell Differentiation/physiology ; DNA-Binding Proteins/genetics/*physiology ; Meristem/physiology ; Models, Biological ; Multigene Family/genetics/*physiology ; *Plant Development ; Plant Roots/physiology ; Plant Stomata/growth & development ; Protein Sorting Signals/genetics/*physiology ; Signal Transduction/*physiology ; Transcription Factors/genetics/*physiology ; }, abstract = {Cell-to-cell communication is integral to the evolution of multicellularity. In plant development, peptide signals relay information coordinating cell proliferation and differentiation. These peptides are often encoded by gene families and bind to corresponding families of receptors. The precise spatiotemporal expression of signals and their cognate receptors underlies developmental patterning, and expressional and biochemical changes over evolutionary time have likely contributed to the refinement and complexity of developmental programs. Here, we discuss two major plant peptide families which have central roles in plant development: the CLAVATA3/ENDOSPERM SURROUNDING REGION (CLE) peptide family and the EPIDERMAL PATTERNING FACTOR (EPF) family. We discuss how specialization has enabled the CLE peptides to modulate stem cell differentiation in various tissue types, and how differing activities of EPF peptides precisely regulate the stomatal developmental program, and we examine the contributions of these peptide families to plant development from an evolutionary perspective.}, } @article {pmid21549955, year = {2011}, author = {Leyser, O}, title = {Auxin, self-organisation, and the colonial nature of plants.}, journal = {Current biology : CB}, volume = {21}, number = {9}, pages = {R331-7}, doi = {10.1016/j.cub.2011.02.031}, pmid = {21549955}, issn = {1879-0445}, mesh = {Biological Transport/physiology ; Indoleacetic Acids/chemistry/*metabolism ; Models, Biological ; *Plant Development ; Plant Growth Regulators/metabolism/*physiology ; Plant Vascular Bundle/*physiology ; }, abstract = {Evolution has provided at least two particularly successful independent solutions to the problems of multicellularity - animals and higher plants. An obvious requirement for successful multicellularity is communication between different parts of the organism, both locally, for example between neighbouring cells, and over very long distances. Recent advances in understanding hormone signalling networks in plants are beginning to reveal how co-ordination of activity across the whole plant body can be achieved despite the lack of a control centre, typical of animal systems. Of particular importance in this distributed regulatory approach are the self-organising properties of the transport system for the plant hormone auxin. This review examines the integrative role of the auxin transport network in co-ordinating plant growth and development.}, } @article {pmid21543332, year = {2011}, author = {Pefani, DE and Dimaki, M and Spella, M and Karantzelis, N and Mitsiki, E and Kyrousi, C and Symeonidou, IE and Perrakis, A and Taraviras, S and Lygerou, Z}, title = {Idas, a novel phylogenetically conserved geminin-related protein, binds to geminin and is required for cell cycle progression.}, journal = {The Journal of biological chemistry}, volume = {286}, number = {26}, pages = {23234-23246}, pmid = {21543332}, issn = {1083-351X}, support = {09-0091/AICR_/Worldwide Cancer Research/United Kingdom ; }, mesh = {Amino Acid Sequence ; Anaphase/physiology ; Animals ; Cell Cycle Proteins/genetics/*metabolism ; Cell Differentiation/physiology ; Cell Nucleus/genetics/*metabolism ; Choroid Plexus/cytology/embryology ; DNA-Binding Proteins/genetics/metabolism ; Geminin ; Gene Expression Regulation, Developmental/physiology ; HeLa Cells ; Humans ; Mice ; Molecular Sequence Data ; Multiprotein Complexes/genetics/*metabolism ; Nuclear Proteins/genetics/*metabolism ; Phylogeny ; S Phase/physiology ; Telencephalon/cytology/embryology ; Transcription Factors ; }, abstract = {Development and homeostasis of multicellular organisms relies on an intricate balance between cell proliferation and differentiation. Geminin regulates the cell cycle by directly binding and inhibiting the DNA replication licensing factor Cdt1. Geminin also interacts with transcriptional regulators of differentiation and chromatin remodelling factors, and its balanced interactions are implicated in proliferation-differentiation decisions during development. Here, we describe Idas (Idas being a cousin of the Gemini in Ancient Greek Mythology), a previously uncharacterised coiled-coil protein related to Geminin. We show that human Idas localizes to the nucleus, forms a complex with Geminin both in cells and in vitro through coiled-coil mediated interactions, and can change Geminin subcellular localization. Idas does not associate with Cdt1 and prevents Geminin from binding to Cdt1 in vitro. Idas depletion from cells affects cell cycle progression; cells accumulate in S phase and are unable to efficiently progress to mitosis. Idas protein levels decrease in anaphase, whereas its overexpression causes mitotic defects. During development, we show that Idas exhibits high level expression in the choroid plexus and the cortical hem of the mouse telencephalon. Our data highlight Idas as a novel Geminin binding partner, implicated in cell cycle progression, and a putative regulator of proliferation-differentiation decisions during development.}, } @article {pmid21542337, year = {2011}, author = {Bukharina, TA and Furman, DP}, title = {[Asymmetric cell division in the morphogenesis of Drosophila melanogaster macrochaetae].}, journal = {Ontogenez}, volume = {42}, number = {2}, pages = {83-93}, pmid = {21542337}, issn = {0475-1450}, mesh = {Animals ; *Biological Evolution ; Cell Division/*physiology ; Drosophila melanogaster ; Morphogenesis/*physiology ; Sensilla/*embryology ; }, abstract = {Asymmetric cell division (ACD) is the basic process which creates diversity in the cells of multicellular organisms. As a result of asymmetric cell division, daughter cells acquire the ability to differentiate and specialize in a given direction, which is different from that of their parent cells and from each other. This type of division is observed in a wide range of living organisms from bacteria to vertebrates. It has been shown that the molecular-genetic control mechanism of ACD is evolutionally conservative. The proteins involved in the process of ACD in different kinds of animals have a high degree of homology. Sensory organs--setae (macrochaetae)--of Drosophila are widely used as a model system for studying the genetic control mechanisms of asymmetric division. Setae located in an orderly manner on the head and body of the fly play the role of mechanoreceptors. Each of them consists of four specialized cells--offspring of the only sensory organ precursor cell (SOPC), which differentiates from the imaginal wing disc at the larval stage of the late third age. The basic differentiation and further specialization of the daughter cells of SOPC is an asymmetric division process. In this summary, experimental data on genes and their products controlling asymmetric division of SOPC and daughter cells, and also the specialization of the latter, have been systemized. The basic mechanisms which determine the time cells enter into asymmetric mitosis and which provides the structural characteristics of the asymmetric division process--the polar distribution of protein determinants Numb and Neuralized--the orientation of the mitotic spindle in relation to these determinants, and the uneven segregation of the determinants into the daughter cells that determines the direction of their development have been discussed.}, } @article {pmid21530299, year = {2011}, author = {Filippini, M and Ortelli, C and Svercel, M and Bagheri, HC}, title = {Interspecies variation in survival and growth of filamentous heterotrophic bacteria in response to UVC radiation.}, journal = {Journal of photochemistry and photobiology. B, Biology}, volume = {103}, number = {3}, pages = {234-242}, doi = {10.1016/j.jphotobiol.2011.03.018}, pmid = {21530299}, issn = {1873-2682}, mesh = {Bacteroidetes/classification/growth & development/metabolism/*radiation effects ; Dose-Response Relationship, Radiation ; Heterotrophic Processes/*radiation effects ; Inovirus/growth & development/metabolism/*radiation effects ; Species Specificity ; Spectrophotometry ; Time Factors ; *Ultraviolet Rays ; }, abstract = {Ultraviolet radiation is an important environmental constraint on the evolution of life. In addition to its harmful effects, ultraviolet radiation plays an important role in generating genetic polymorphisms and acting as a selective agent. Understanding how prokaryotes cope with high radiation can give insights on the evolution of life on Earth. Four representative filamentous bacteria from the family Cytophagaceae with different pigmentation were selected and exposed to different doses of UVC radiation (15-32,400Jm(-2)). The effect of UVC radiation on bacterial survival, growth and morphology were investigated. Results showed high survival in response to UVC for Rudanella lutea and Fibrisoma limi, whereas low survival was observed for Fibrella aestuarina and Spirosoma linguale. S. linguale showed slow growth recovery after ultraviolet exposure, R. lutea and F. limi showed intermediate growth recovery, while F. aestuarina had the fastest recovery among the four tested bacteria. In terms of survival, S. linguale was the most sensitive bacterium whereas R. lutea and F. limi were better at coping with UVC stress. The latter two resumed growth even after 2h exposure (∼10,800Jm(-2)). Additionally, the ability to form multicellular filaments after exposure was tested using two bacteria: one representative of the high (R. lutea) and one of the low (F. aestuarina) survival rates. The ability to elongate filaments due to cell division was preserved but modified. In R. lutea 10min exposure reduced the average filament length. The opposite was observed in F. aestuarina, where the 5 and 10min exposures increased the average filament length. R. lutea and F. limi are potential candidates for further research into survival and resistance to ultraviolet radiation stress.}, } @article {pmid21527387, year = {2011}, author = {Leigh, JW and Schliep, K and Lopez, P and Bapteste, E}, title = {Let them fall where they may: congruence analysis in massive phylogenetically messy data sets.}, journal = {Molecular biology and evolution}, volume = {28}, number = {10}, pages = {2773-2785}, doi = {10.1093/molbev/msr110}, pmid = {21527387}, issn = {1537-1719}, mesh = {*Algorithms ; Archaea/genetics ; Bacteria/genetics ; Bayes Theorem ; *Cluster Analysis ; Computational Biology/*methods ; Computer Simulation ; *Databases, Genetic ; Evolution, Molecular ; Fungi/genetics ; Genetic Markers ; Genetic Variation ; *Phylogeny ; Sequence Alignment ; }, abstract = {Interest in congruence in phylogenetic data has largely focused on issues affecting multicellular organisms, and animals in particular, in which the level of incongruence is expected to be relatively low. In addition, assessment methods developed in the past have been designed for reasonably small numbers of loci and scale poorly for larger data sets. However, there are currently over a thousand complete genome sequences available and of interest to evolutionary biologists, and these sequences are predominantly from microbial organisms, whose molecular evolution is much less frequently tree-like than that of multicellular life forms. As such, the level of incongruence in these data is expected to be high. We present a congruence method that accommodates both very large numbers of genes and high degrees of incongruence. Our method uses clustering algorithms to identify subsets of genes based on similarity of phylogenetic signal. It involves only a single phylogenetic analysis per gene, and therefore, computation time scales nearly linearly with the number of genes in the data set. We show that our method performs very well with sets of sequence alignments simulated under a wide variety of conditions. In addition, we present an analysis of core genes of prokaryotes, often assumed to have been largely vertically inherited, in which we identify two highly incongruent classes of genes. This result is consistent with the complexity hypothesis.}, } @article {pmid21521246, year = {2012}, author = {Brückner, S and Mösch, HU}, title = {Choosing the right lifestyle: adhesion and development in Saccharomyces cerevisiae.}, journal = {FEMS microbiology reviews}, volume = {36}, number = {1}, pages = {25-58}, doi = {10.1111/j.1574-6976.2011.00275.x}, pmid = {21521246}, issn = {1574-6976}, mesh = {*Cell Adhesion ; Gene Expression Regulation, Fungal ; Membrane Proteins/genetics/metabolism ; Saccharomyces cerevisiae/growth & development/*physiology ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; }, abstract = {The budding yeast Saccharomyces cerevisiae is a eukaryotic microorganism that is able to choose between different unicellular and multicellular lifestyles. The potential of individual yeast cells to switch between different growth modes is advantageous for optimal dissemination, protection and substrate colonization at the population level. A crucial step in lifestyle adaptation is the control of self- and foreign adhesion. For this purpose, S. cerevisiae contains a set of cell wall-associated proteins, which confer adhesion to diverse biotic and abiotic surfaces. Here, we provide an overview of different aspects of S. cerevisiae adhesion, including a detailed description of known lifestyles, recent insights into adhesin structure and function and an outline of the complex regulatory network for adhesin gene regulation. Our review shows that S. cerevisiae is a model system suitable for studying not only the mechanisms and regulation of cell adhesion, but also the role of this process in microbial development, ecology and evolution.}, } @article {pmid21512106, year = {2011}, author = {Piskurek, O and Jackson, DJ}, title = {Tracking the ancestry of a deeply conserved eumetazoan SINE domain.}, journal = {Molecular biology and evolution}, volume = {28}, number = {10}, pages = {2727-2730}, doi = {10.1093/molbev/msr115}, pmid = {21512106}, issn = {1537-1719}, mesh = {Animals ; Base Sequence ; *DNA Transposable Elements ; Evolution, Molecular ; Invertebrates/classification/*genetics ; *Long Interspersed Nucleotide Elements ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; *Short Interspersed Nucleotide Elements ; }, abstract = {Transposable elements (TEs), such as short interspersed elements (SINEs), evolve rapidly and are generally restricted to specific lineages. Here, we demonstrate that a central core of the previously described Deu-domain located within DeuSINEs (Nishihara et al. 2006) is widely distributed throughout the Metazoa. We characterize five new SINEs with this core sequence from the genomes of cnidarians, molluscs, annelids, and arthropods. Because this domain can be traced back to the cnidarian-bilaterian split >600 Ma, we propose naming it the "Nin" domain (the meaning of the Japanese character "Nin" is to endure and hide). Given that conserved noncoding DNA, such as that derived from the activity of SINEs, can be functionally relevant for the host genome (Sasaki et al. 2008), our findings highlight the need to understand these functions and the roles they may have played in supporting the evolution of multicellular genomes.}, } @article {pmid21506007, year = {2011}, author = {Sinkovics, JG}, title = {Horizontal gene transfers with or without cell fusions in all categories of the living matter.}, journal = {Advances in experimental medicine and biology}, volume = {714}, number = {}, pages = {5-89}, pmid = {21506007}, issn = {0065-2598}, mesh = {Animals ; Archaea/genetics ; Cell Fusion ; Cell Survival ; Epithelial-Mesenchymal Transition ; *Gene Transfer, Horizontal ; Herpesviridae/genetics ; Humans ; Mimiviridae/genetics ; Neoplasms/pathology/therapy ; Proto-Oncogenes ; Retroelements ; Vibrio cholerae/genetics ; Virulence/genetics ; }, abstract = {This article reviews the history of widespread exchanges of genetic segments initiated over 3 billion years ago, to be part of their life style, by sphero-protoplastic cells, the ancestors of archaea, prokaryota, and eukaryota. These primordial cells shared a hostile anaerobic and overheated environment and competed for survival. "Coexist with, or subdue and conquer, expropriate its most useful possessions, or symbiose with it, your competitor" remain cellular life's basic rules. This author emphasizes the role of viruses, both in mediating cell fusions, such as the formation of the first eukaryotic cell(s) from a united crenarchaeon and prokaryota, and the transfer of host cell genes integrated into viral (phages) genomes. After rising above the Darwinian threshold, rigid rules of speciation and vertical inheritance in the three domains of life were established, but horizontal gene transfers with or without cell fusions were never abolished. The author proves with extensive, yet highly selective documentation, that not only unicellular microorganisms, but the most complex multicellular entities of the highest ranks resort to, and practice, cell fusions, and donate and accept horizontally (laterally) transferred genes. Cell fusions and horizontally exchanged genetic materials remain the fundamental attributes and inherent characteristics of the living matter, whether occurring accidentally or sought after intentionally. These events occur to cells stagnating for some 3 milliard years at a lower yet amazingly sophisticated level of evolution, and to cells achieving the highest degree of differentiation, and thus functioning in dependence on the support of a most advanced multicellular host, like those of the human brain. No living cell is completely exempt from gene drains or gene insertions.}, } @article {pmid21504890, year = {2011}, author = {DeBarry, JD and Kissinger, JC}, title = {Jumbled genomes: missing Apicomplexan synteny.}, journal = {Molecular biology and evolution}, volume = {28}, number = {10}, pages = {2855-2871}, pmid = {21504890}, issn = {1537-1719}, support = {R01 AI068908/AI/NIAID NIH HHS/United States ; R01 AI068908-04/AI/NIAID NIH HHS/United States ; R01AI068908/AI/NIAID NIH HHS/United States ; }, mesh = {Apicomplexa/*genetics ; Computer Simulation ; DNA Transposable Elements ; *Evolution, Molecular ; Gene Deletion ; Gene Rearrangement ; *Genome ; Genomics ; Phylogeny ; Synteny/*genetics ; }, abstract = {Whole-genome comparisons provide insight into genome evolution by informing on gene repertoires, gene gains/losses, and genome organization. Most of our knowledge about eukaryotic genome evolution is derived from studies of multicellular model organisms. The eukaryotic phylum Apicomplexa contains obligate intracellular protist parasites responsible for a wide range of human and veterinary diseases (e.g., malaria, toxoplasmosis, and theileriosis). We have developed an in silico protein-encoding gene based pipeline to investigate synteny across 12 apicomplexan species from six genera. Genome rearrangement between lineages is extensive. Syntenic regions (conserved gene content and order) are rare between lineages and appear to be totally absent across the phylum, with no group of three genes found on the same chromosome and in the same order within 25 kb up- and downstream of any orthologous genes. Conserved synteny between major lineages is limited to small regions in Plasmodium and Theileria/Babesia species, and within these conserved regions, there are a number of proteins putatively targeted to organelles. The observed overall lack of synteny is surprising considering the divergence times and the apparent absence of transposable elements (TEs) within any of the species examined. TEs are ubiquitous in all other groups of eukaryotes studied to date and have been shown to be involved in genomic rearrangements. It appears that there are different criteria governing genome evolution within the Apicomplexa relative to other well-studied unicellular and multicellular eukaryotes.}, } @article {pmid21504495, year = {2011}, author = {Shea, N and Pen, I and Uller, T}, title = {Three epigenetic information channels and their different roles in evolution.}, journal = {Journal of evolutionary biology}, volume = {24}, number = {6}, pages = {1178-1187}, pmid = {21504495}, issn = {1420-9101}, support = {/WT_/Wellcome Trust/United Kingdom ; 086041/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Adaptation, Biological ; *Biological Evolution ; *Epigenesis, Genetic ; Inheritance Patterns ; Phenotype ; Selection, Genetic ; }, abstract = {There is increasing evidence for epigenetically mediated transgenerational inheritance across taxa. However, the evolutionary implications of such alternative mechanisms of inheritance remain unclear. Herein, we show that epigenetic mechanisms can serve two fundamentally different functions in transgenerational inheritance: (i) selection-based effects, which carry adaptive information in virtue of selection over many generations of reliable transmission; and (ii) detection-based effects, which are a transgenerational form of adaptive phenotypic plasticity. The two functions interact differently with a third form of epigenetic information transmission, namely information about cell state transmitted for somatic cell heredity in multicellular organisms. Selection-based epigenetic information is more likely to conflict with somatic cell inheritance than is detection-based epigenetic information. Consequently, the evolutionary implications of epigenetic mechanisms are different for unicellular and multicellular organisms, which underscores the conceptual and empirical importance of distinguishing between these two different forms of transgenerational epigenetic effect.}, } @article {pmid21501754, year = {2011}, author = {Farge, E}, title = {Mechanotransduction in development.}, journal = {Current topics in developmental biology}, volume = {95}, number = {}, pages = {243-265}, doi = {10.1016/B978-0-12-385065-2.00008-6}, pmid = {21501754}, issn = {1557-8933}, mesh = {Animals ; Arabidopsis ; Biomechanical Phenomena ; Cell Differentiation/*physiology ; Cell Movement/*physiology ; Cytoskeleton/*physiology ; Drosophila ; Embryonic Development/genetics/*physiology ; Mechanotransduction, Cellular/*physiology ; Mice ; *Models, Biological ; Morphogenesis/genetics/*physiology ; Xenopus ; }, abstract = {Biochemical patterning and morphogenetic movements coordinate the design of embryonic development. The molecular processes that pattern and closely control morphogenetic movements are today becoming well understood. Recent experimental evidence demonstrates that mechanical cues generated by morphogenesis activate mechanotransduction pathways, which in turn regulate cytoskeleton remodeling, cell proliferation, tissue differentiation. From Drosophila oocytes and embryos to Xenopus and mouse embryos and Arabidopsis meristem, here we review the developmental processes known to be activated in vivo by the mechanical strains associated to embryonic multicellular tissue morphogenesis. We describe the genetic, mechanical, and magnetic tools that have allowed the testing of mechanical induction in development by a step-by-step uncoupling of genetic inputs from mechanical inputs in embryogenesis. We discuss the known underlying molecular mechanisms involved in such mechanotransduction processes, including the Armadillo/β-catenin activation of Twist and the Fog-dependent stabilization of Myosin-II. These mechanotransduction processes are associated with a variety of physiological functions, such as mid-gut differentiation, mesoderm invagination and skeletal joint differentiation in embryogenesis, cell migration and internal pressure regulation during oogenesis, and meristem morphogenesis. We describe how the conservation of associated mechanosensitive pathways in embryonic and adult tissues opens new perspectives on mechanical involvement, potentially in evolution, and in cancer progression.}, } @article {pmid21501571, year = {2011}, author = {Vincensini, L and Blisnick, T and Bastin, P}, title = {[The importance of model organisms to study cilia and flagella biology].}, journal = {Biologie aujourd'hui}, volume = {205}, number = {1}, pages = {5-28}, doi = {10.1051/jbio/2011005}, pmid = {21501571}, issn = {2105-0678}, mesh = {Animals ; Cell Movement ; Cilia/genetics/*physiology/ultrastructure ; Flagella/genetics/*physiology/ultrastructure ; Genetic Diseases, Inborn ; Humans ; Mice ; Models, Animal ; *Models, Biological ; Mutation ; Sensation ; }, abstract = {Cilia and flagella are ubiquitous organelles that protrude from the surfaces of many cells, and whose architecture is highly conserved from protists to humans. These complex organelles, composed of over 500 proteins, can be either immotile or motile. They are involved in a myriad of biological processes, including sensing (non-motile cilia) and/or cell motility or movement of extracellular fluids (motile cilia). The ever-expanding list of human diseases linked to defective cilia illustrates the functional importance of cilia and flagella. These ciliopathies are characterised by an impressive diversity of symptoms and an often complex genetic etiology. A precise knowledge of cilia and flagella biology is thus critical to better understand these pathologies. However, multi-ciliated cells are terminally differentiated and difficult to manipulate, and a primary cilium is assembled only when the cell exits from the cell cycle. In this context the use of model organisms, that relies on the high degree of structural but also of molecular conservation of these organelles across evolution, is instrumental to decipher the many facets of cilia and flagella biology. In this review, we highlight the specific strengths of the main model organisms to investigate the molecular composition, mode of assembly, sensing and motility mechanisms and functions of cilia and flagella. Pioneering studies carried out in the green alga Chlamydomonas established the link between cilia and several genetic diseases. Moreover, multicellular organisms such as mouse, zebrafish, Xenopus, C. elegans or Drosophila, and protists like Paramecium, Tetrahymena and Trypanosoma or Leishmania each bring specific advantages to the study of cilium biology. For example, the function of genes involved in primary ciliary dyskinesia (due to defects in ciliary motility) can be efficiently assessed in trypanosomes.}, } @article {pmid21494661, year = {2011}, author = {Almendinger, J and Doukoumetzidis, K and Kinchen, JM and Kaech, A and Ravichandran, KS and Hengartner, MO}, title = {A conserved role for SNX9-family members in the regulation of phagosome maturation during engulfment of apoptotic cells.}, journal = {PloS one}, volume = {6}, number = {4}, pages = {e18325}, pmid = {21494661}, issn = {1932-6203}, mesh = {Animals ; *Apoptosis ; Caenorhabditis elegans/*cytology/*metabolism/ultrastructure ; Caenorhabditis elegans Proteins/chemistry/*metabolism ; Conserved Sequence/*genetics ; Mice ; Models, Biological ; NIH 3T3 Cells ; *Phagocytosis ; Phagosomes/*metabolism ; Protein Structure, Tertiary ; Protein Transport ; Sorting Nexins/chemistry/*metabolism ; Structure-Activity Relationship ; rab5 GTP-Binding Proteins/metabolism ; }, abstract = {Clearance of apoptotic cells is of key importance during development, tissue homeostasis and wound healing in multi-cellular animals. Genetic studies in the nematode Caenorhabditis elegans have identified a set of genes involved in the early steps of cell clearance, in particular the recognition and internalization of apoptotic cells. A pathway that orchestrates the maturation of phagosomes containing ingested apoptotic cells in the worm has recently been described. However, many steps in this pathway remain elusive. Here we show that the C. elegans SNX9-family member LST-4 (lateral signaling target) and its closest mammalian orthologue SNX33 play an evolutionary conserved role during apoptotic cell corpse clearance. In lst-4 deficient worms, internalized apoptotic cells accumulated within non-acidified, DYN-1-positive but RAB-5-negative phagosomes. Genetically, we show that LST-4 functions at the same step as DYN-1 during corpse removal, upstream of the GTPase RAB-5. We further show that mammalian SNX33 rescue C. elegans lst-4 mutants and that overexpression of truncated SNX33 fragments interfered with phagosome maturation in a mammalian cell system. Taken together, our genetic and cell biological analyses suggest that LST-4 is recruited through a combined activity of DYN-1 and VPS-34 to the early phagosome membrane, where it cooperates with DYN-1 to promote recruitment/retention of RAB-5 on the early phagosomal membrane during cell corpse clearance. The functional conservation between LST-4 and SNX33 indicate that these early steps of apoptotic phagosome maturation are likely conserved through evolution.}, } @article {pmid21494601, year = {2011}, author = {Santini, S and Claverie, JM and Mouz, N and Rousselle, T and Maza, C and Monchois, V and Abergel, C}, title = {The conserved Candida albicans CA3427 gene product defines a new family of proteins exhibiting the generic periplasmic binding protein structural fold.}, journal = {PloS one}, volume = {6}, number = {4}, pages = {e18528}, pmid = {21494601}, issn = {1932-6203}, mesh = {Binding Sites ; Candida albicans/*genetics ; Conserved Sequence/*genetics ; Crystallography, X-Ray ; Evolution, Molecular ; Fungal Proteins/*chemistry/*genetics ; Genes, Fungal/*genetics ; Ligands ; Models, Molecular ; *Multigene Family ; Periplasmic Binding Proteins/*chemistry/metabolism ; Phylogeny ; Protein Structure, Secondary ; Sequence Alignment ; Structural Homology, Protein ; }, abstract = {Nosocomial diseases due to Candida albicans infections are in constant rise in hospitals, where they cause serious complications to already fragile intensive care patients. Antifungal drug resistance is fast becoming a serious issue due to the emergence of strains resistant to currently available antifungal agents. Thus the urgency to identify new potential protein targets, the function and structure of which may guide the development of new antifungal drugs. In this context, we initiated a comparative genomics study in search of promising protein coding genes among the most conserved ones in reference fungal genomes. The CA3427 gene was selected on the basis of its presence among pathogenic fungi contrasting with its absence in the non pathogenic Saccharomyces cerevisiae. We report the crystal 3D-structure of the Candida albicans CA3427 protein at 2.1 Å resolution. The combined analysis of its sequence and structure reveals a structural fold originally associated with periplasmic binding proteins. The CA3427 structure highlights a binding site located between the two protein domains, corresponding to a sequence segment conserved among fungi. Two crystal forms of CA3427 were found, suggesting that the presence or absence of a ligand at the proposed binding site might trigger a "Venus flytrap" motion, coupled to the previously described activity of bacterial periplasmic binding proteins. The conserved binding site defines a new subfamily of periplasmic binding proteins also found in many bacteria of the bacteroidetes division, in a choanoflagellate (a free-living unicellular and colonial flagellate eukaryote) and in a placozoan (the closest multicellular relative of animals). A phylogenetic analysis suggests that this gene family originated in bacteria before its horizontal transfer to an ancestral eukaryote prior to the radiation of fungi. It was then lost by the Saccharomycetales which include Saccharomyces cerevisiae.}, } @article {pmid21490597, year = {2011}, author = {Strother, PK and Battison, L and Brasier, MD and Wellman, CH}, title = {Earth's earliest non-marine eukaryotes.}, journal = {Nature}, volume = {473}, number = {7348}, pages = {505-509}, pmid = {21490597}, issn = {1476-4687}, mesh = {Aquatic Organisms ; *Biological Evolution ; Biota ; *Ecosystem ; Eukaryota/*classification/cytology/*isolation & purification ; *Fossils ; *Fresh Water ; Geologic Sediments/analysis/chemistry ; History, Ancient ; Scotland ; }, abstract = {The existence of a terrestrial Precambrian (more than 542 Myr ago) biota has been largely inferred from indirect chemical and geological evidence associated with palaeosols, the weathering of clay minerals and microbially induced sedimentary structures in siliciclastic sediments. Direct evidence of fossils within rocks of non-marine origin in the Precambrian is exceedingly rare. The most widely cited example comprises a single report of morphologically simple mineralized tubes and spheres interpreted as cyanobacteria, obtained from 1,200-Myr-old palaeokarst in Arizona. Organic-walled microfossils were first described from the non-marine Torridonian (1.2-1.0 Gyr ago) sequence of northwest Scotland in 1907. Subsequent studies found few distinctive taxa-a century later, the Torridonian microflora is still being characterized as primarily nondescript "leiospheres". We have comprehensively sampled grey shales and phosphatic nodules throughout the Torridonian sequence. Here we report the recovery of large populations of diverse organic-walled microfossils extracted by acid maceration, complemented by studies using thin sections of phosphatic nodules that yield exceptionally detailed three-dimensional preservation. These assemblages contain multicellular structures, complex-walled cysts, asymmetric organic structures, and dorsiventral, compressed organic thalli, some approaching one millimetre in diameter. They offer direct evidence of eukaryotes living in freshwater aquatic and subaerially exposed habitats during the Proterozoic era. The apparent dominance of eukaryotes in non-marine settings by 1 Gyr ago indicates that eukaryotic evolution on land may have commenced far earlier than previously thought.}, } @article {pmid21490246, year = {2011}, author = {Bekal, S and Domier, LL and Niblack, TL and Lambert, KN}, title = {Discovery and initial analysis of novel viral genomes in the soybean cyst nematode.}, journal = {The Journal of general virology}, volume = {92}, number = {Pt 8}, pages = {1870-1879}, doi = {10.1099/vir.0.030585-0}, pmid = {21490246}, issn = {1465-2099}, mesh = {Animals ; Base Sequence ; *Genome, Viral ; Molecular Sequence Data ; Phylogeny ; RNA Viruses/classification/*genetics/*isolation & purification ; Tylenchoidea/*virology ; Viral Proteins/genetics ; }, abstract = {Nematodes are the most abundant multicellular animals on earth, yet little is known about their natural viral pathogens. To date, only two nematode virus genomes have been reported. Consequently, nematode viruses have been overlooked as important biotic factors in the study of nematode ecology. Here, we show that one plant parasitic nematode species, Heterodera glycines, the soybean cyst nematode (SCN), harbours four different RNA viruses. The nematode virus genomes were discovered in the SCN transcriptome after high-throughput sequencing and assembly. All four viruses have negative-sense RNA genomes, and are distantly related to nyaviruses and bornaviruses, rhabdoviruses, bunyaviruses and tenuiviruses. Some members of these families replicate in and are vectored by insects, and can cause significant diseases in animals and plants. The novel viral sequences were detected in both eggs and the second juvenile stage of SCN, suggesting that these viruses are transmitted vertically. While there was no evidence of integration of viral sequences into the nematode genome, we indeed detected transcripts from these viruses by using quantitative PCR. These data are the first finding of virus genomes in parasitic nematodes. This discovery highlights the need for further exploration for nematode viruses in all tropic groups of these diverse and abundant animals, to determine how the presence of these viruses affects the fitness of the nematode, strategies of viral transmission and mechanisms of viral pathogenesis.}, } @article {pmid21487402, year = {2011}, author = {Xavier, JB}, title = {Social interaction in synthetic and natural microbial communities.}, journal = {Molecular systems biology}, volume = {7}, number = {}, pages = {483}, pmid = {21487402}, issn = {1744-4292}, support = {U54 CA148967/CA/NCI NIH HHS/United States ; 1U54CA148967-01/CA/NCI NIH HHS/United States ; }, mesh = {*Biological Evolution ; *Ecosystem ; Gene Expression Regulation ; Immune System/physiology ; *Microbial Interactions ; Models, Biological ; Neoplasms/pathology ; }, abstract = {Social interaction among cells is essential for multicellular complexity. But how do molecular networks within individual cells confer the ability to interact? And how do those same networks evolve from the evolutionary conflict between individual- and population-level interests? Recent studies have dissected social interaction at the molecular level by analyzing both synthetic and natural microbial populations. These studies shed new light on the role of population structure for the evolution of cooperative interactions and revealed novel molecular mechanisms that stabilize cooperation among cells. New understanding of populations is changing our view of microbial processes, such as pathogenesis and antibiotic resistance, and suggests new ways to fight infection by exploiting social interaction. The study of social interaction is also challenging established paradigms in cancer evolution and immune system dynamics. Finding similar patterns in such diverse systems suggests that the same 'social interaction motifs' may be general to many cell populations.}, } @article {pmid21487044, year = {2011}, author = {Sachs, RK and Johnsson, K and Hahnfeldt, P and Luo, J and Chen, A and Hlatky, L}, title = {A multicellular basis for the origination of blast crisis in chronic myeloid leukemia.}, journal = {Cancer research}, volume = {71}, number = {8}, pages = {2838-2847}, pmid = {21487044}, issn = {1538-7445}, support = {R01 GM068423/GM/NIGMS NIH HHS/United States ; U54 CA149233/CA/NCI NIH HHS/United States ; U54 CA149233-01/CA/NCI NIH HHS/United States ; 1U54CA149233/CA/NCI NIH HHS/United States ; }, mesh = {Blast Crisis/*pathology ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*pathology ; *Models, Biological ; }, abstract = {Chronic myeloid leukemia (CML) is characterized by a specific chromosome translocation, and its pathobiology is considered comparatively well understood. Thus, quantitative analysis of CML and its progression to blast crisis may help elucidate general mechanisms of carcinogenesis and cancer progression. Hitherto, it has been widely postulated that CML blast crisis originates mainly via cell-autonomous mechanisms such as secondary mutations or genomic instability. However, recent results suggest that carcinogenic transformation may be an inherently multicellular event, in departure from the classic unicellular paradigm. We investigate this possibility in the case of blast crisis origination in CML. A quantitative, mechanistic cell population dynamics model was employed. This model used recent data on imatinib-treated CML; it also used earlier clinical data, not previously incorporated into current mathematical CML/imatinib models. With the pre-imatinib data, which include results on many more blast crises, we obtained evidence that the driving mechanism for blast crisis origination is a cooperation between specific cell types. Assuming leukemic-normal interactions resulted in a statistically significant improvement over assuming either cell-autonomous mechanisms or interactions between leukemic cells. This conclusion was robust with regard to changes in the model's adjustable parameters. Application of the results to patients treated with imatinib suggests that imatinib may act not only on malignant blast precursors, but also, to a limited degree, on the malignant blasts themselves.}, } @article {pmid21485507, year = {2011}, author = {Vilgelm, AE and Zaika, AI and Prasolov, VS}, title = {[The coordinated interaction of multifunctional members of p53 family determines many key processes in multicellular organisms].}, journal = {Molekuliarnaia biologiia}, volume = {45}, number = {1}, pages = {180-197}, pmid = {21485507}, issn = {0026-8984}, mesh = {Animals ; DNA-Binding Proteins/genetics/*metabolism ; Evolution, Molecular ; Humans ; Mice ; *Multigene Family ; Neoplasms/genetics/*metabolism ; Nuclear Proteins/genetics/*metabolism ; Phosphoproteins/genetics/*metabolism ; Trans-Activators/genetics/*metabolism ; Transcription Factors ; Tumor Protein p73 ; Tumor Suppressor Protein p53/genetics/*metabolism ; Tumor Suppressor Proteins/genetics/*metabolism ; }, abstract = {First time p53 was found in the complex with viral large T-antigene in the cells transformed by small DNA virus SV40. The cloning of p53 cDNA was done in the beginning of eighties and soon after that the whole p53 gene was cloned. The p53 family is comprised of three genes: TP53,TP63 and TP73, each of which is expressed as a set of structurally and functionally different isoforms. All of them intensively interact with each other forming a united functional network of proteins. In this review we discuss evolution of the p53 family and significance of all its members in embryonic development, reproduction, regeneration, regulation of aging and life span, as well as in the body's defense against cancer. With special attention we review the role of less studied members of the p53 family: p63 and p73, in oncogenesis and tumor progression and show that different isoforms of these proteins might exert a contrary effect on these processes.}, } @article {pmid21472016, year = {2011}, author = {Herlemann, DP and Labrenz, M and Jürgens, K and Bertilsson, S and Waniek, JJ and Andersson, AF}, title = {Transitions in bacterial communities along the 2000 km salinity gradient of the Baltic Sea.}, journal = {The ISME journal}, volume = {5}, number = {10}, pages = {1571-1579}, pmid = {21472016}, issn = {1751-7370}, mesh = {Bacteria/*classification/genetics/*isolation & purification ; Baltic States ; Biodiversity ; Biota ; Fresh Water/*microbiology ; Oceans and Seas ; Phylogeny ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Seawater/*microbiology ; }, abstract = {Salinity is a major factor controlling the distribution of biota in aquatic systems, and most aquatic multicellular organisms are either adapted to life in saltwater or freshwater conditions. Consequently, the saltwater-freshwater mixing zones in coastal or estuarine areas are characterized by limited faunal and floral diversity. Although changes in diversity and decline in species richness in brackish waters is well documented in aquatic ecology, it is unknown to what extent this applies to bacterial communities. Here, we report a first detailed bacterial inventory from vertical profiles of 60 sampling stations distributed along the salinity gradient of the Baltic Sea, one of world's largest brackish water environments, generated using 454 pyrosequencing of partial (400 bp) 16S rRNA genes. Within the salinity gradient, bacterial community composition altered at broad and finer-scale phylogenetic levels. Analogous to faunal communities within brackish conditions, we identified a bacterial brackish water community comprising a diverse combination of freshwater and marine groups, along with populations unique to this environment. As water residence times in the Baltic Sea exceed 3 years, the observed bacterial community cannot be the result of mixing of fresh water and saltwater, but our study represents the first detailed description of an autochthonous brackish microbiome. In contrast to the decline in the diversity of multicellular organisms, reduced bacterial diversity at brackish conditions could not be established. It is possible that the rapid adaptation rate of bacteria has enabled a variety of lineages to fill what for higher organisms remains a challenging and relatively unoccupied ecological niche.}, } @article {pmid21460558, year = {2011}, author = {Durand, PM and Rashidi, A and Michod, RE}, title = {How an organism dies affects the fitness of its neighbors.}, journal = {The American naturalist}, volume = {177}, number = {2}, pages = {224-232}, doi = {10.1086/657686}, pmid = {21460558}, issn = {1537-5323}, mesh = {Animals ; Apoptosis/*physiology ; Chlamydomonas reinhardtii/*cytology/genetics/*physiology ; Culture Media, Conditioned ; Genetic Fitness ; Reactive Oxygen Species ; Time Factors ; }, abstract = {Programmed cell death (PCD), a genetically regulated cell suicide program, is ubiquitous in the living world. In contrast to multicellular organisms, in which cells cooperate for the good of the organism, in unicells the cell is the organism and PCD presents a fundamental evolutionary problem. Why should an organism actively kill itself as opposed to dying in a nonprogrammed way? Proposed arguments vary from PCD in unicells being maladaptive to the assumption that it is an extreme form of altruism. To test whether PCD could be beneficial to nearby cells, we induced programmed and nonprogrammed death in the unicellular green alga Chlamydomonas reinhardtii. Cellular contents liberated during non-PCD are detrimental to others, while the contents released during PCD are beneficial. The number of cells in growing cultures was used to measure fitness. Thermostability studies revealed that the beneficial effect of the PCD supernatant most likely involves simple heat-stable biomolecules. Non-PCD supernatant contains heat-sensitive molecules like cellular proteases and chlorophyll. These data indicate that the mode of death affects the origin and maintenance of PCD. The way in which an organism dies can have beneficial or deleterious effects on the fitness of its neighbors.}, } @article {pmid21460544, year = {2011}, author = {Pollitt, LC and Mideo, N and Drew, DR and Schneider, P and Colegrave, N and Reece, SE}, title = {Competition and the evolution of reproductive restraint in malaria parasites.}, journal = {The American naturalist}, volume = {177}, number = {3}, pages = {358-367}, pmid = {21460544}, issn = {1537-5323}, support = {//Wellcome Trust/United Kingdom ; 082234//Wellcome Trust/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; *Competitive Behavior ; Gametogenesis ; Genetic Variation ; Genotype ; Malaria/*parasitology/*transmission ; Male ; Metamorphosis, Biological ; Mice ; *Microbial Interactions ; Phenotype ; Plasmodium chabaudi/*genetics/growth & development/*physiology ; Reproduction ; }, abstract = {All organisms must trade off resource allocation between different life processes that determine their survival and reproduction. Malaria parasites replicate asexually in the host but must produce sexual stages to transmit between hosts. Because different specialized stages are required for these functions, the division of resources between these life-history components is a key problem for natural selection to solve. Despite the medical and economic importance of these parasites, their reproductive strategies remain poorly understood and often seem counterintuitive. Here, we tested recent theory predicting that in-host competition shapes how parasites trade off investment in in-host replication relative to between-host transmission. We demonstrate, across several genotypes, that Plasmodium chabaudi parasites detect the presence of competing genotypes and facultatively respond by reducing their investment in sexual stages in the manner predicted to maximize their competitive ability. Furthermore, we show that genotypes adjust their allocation to sexual stages in line with the availability of exploitable red blood cell resources. Our findings are predicted by evolutionary theory developed to explain life-history trade-offs in more traditionally studied multicellular taxa and suggest that the answer to the long-standing question of why so few transmission stages are produced is that in most natural infections heavy investment in reproduction may compromise in-host survival.}, } @article {pmid21453486, year = {2011}, author = {Romeralo, M and Cavender, JC and Landolt, JC and Stephenson, SL and Baldauf, SL}, title = {An expanded phylogeny of social amoebas (Dictyostelia) shows increasing diversity and new morphological patterns.}, journal = {BMC evolutionary biology}, volume = {11}, number = {}, pages = {84}, pmid = {21453486}, issn = {1471-2148}, mesh = {Biological Evolution ; Dictyosteliida/classification/*cytology/*genetics ; *Phylogeny ; RNA, Protozoan/genetics ; RNA, Ribosomal/genetics ; }, abstract = {BACKGROUND: Social Amoebae or Dictyostelia are eukaryotic microbes with a unique life cycle consisting of both uni- and multicellular stages. They have long fascinated molecular, developmental and evolutionary biologists, and Dictyostelium discoideum is now one of the most widely studied eukaryotic microbial models. The first molecular phylogeny of Dictyostelia included most of the species known at the time and suggested an extremely deep taxon with a molecular depth roughly equivalent to Metazoa. The group was also shown to consist of four major clades, none of which correspond to traditional genera. Potential morphological justification was identified for three of the four major groups, on the basis of which tentative names were assigned.

RESULTS: Over the past four years, the Mycetozoan Global Biodiversity Survey has identified many new isolates that appear to be new species of Dictyostelia, along with numerous isolates of previously described species. We have determined 18S ribosomal RNA gene sequences for all of these new isolates. Phylogenetic analyses of these data show at least 50 new species, and these arise from throughout the dictyostelid tree breaking up many previously isolated long branches. The resulting tree now shows eight well-supported major groups instead of the original four. The new species also expand the known morphological diversity of the previously established four major groups, violating nearly all previously suggested deep morphological patterns.

CONCLUSIONS: A greatly expanded phylogeny of Dictyostelia now shows even greater morphological plasticity at deep taxonomic levels. In fact, there now seem to be no obvious deep evolutionary trends across the group. However at a finer level, patterns in morphological character evolution are beginning to emerge. These results also suggest that there is a far greater diversity of Dictyostelia yet to be discovered, including novel morphologies.}, } @article {pmid21443629, year = {2011}, author = {Shockey, J and Browse, J}, title = {Genome-level and biochemical diversity of the acyl-activating enzyme superfamily in plants.}, journal = {The Plant journal : for cell and molecular biology}, volume = {66}, number = {1}, pages = {143-160}, doi = {10.1111/j.1365-313X.2011.04512.x}, pmid = {21443629}, issn = {1365-313X}, mesh = {Arabidopsis/enzymology/genetics ; Coenzyme A Ligases/*genetics/metabolism ; *Evolution, Molecular ; Fatty Acids/biosynthesis ; Gene Duplication ; Genome, Plant ; *Multigene Family ; Phylogeny ; Plants/*enzymology/genetics ; Plastids/metabolism ; }, abstract = {In higher plants, the superfamily of carboxyl-CoA ligases and related proteins, collectively called acyl activating enzymes (AAEs), has evolved to provide enzymes for many pathways of primary and secondary metabolism and for the conjugation of hormones to amino acids. Across the superfamily there is only limited sequence similarity, but a series of highly conserved motifs, including the AMP-binding domain, make it easy to identify members. These conserved motifs are best understood in terms of the unique domain-rotation architecture that allows AAE enzymes to catalyze the two distinct steps of the CoA ligase reaction. Arabidopsis AAE sequences were used to identify the AAE gene families in the sequenced genomes of green algae, mosses, and trees; the size of the respective families increased with increasing degree of organismal cellular complexity, size, and generation time. Large-scale genome duplications and small-scale tandem gene duplications have contributed to AAE gene family complexity to differing extents in each of the multicellular species analyzed. Gene duplication and evolution of novel functions in Arabidopsis appears to have occurred rapidly, because acquisition of new substrate specificity is relatively easy in this class of proteins. Convergent evolution has also occurred between members of distantly related clades. These features of the AAE superfamily make it difficult to use homology searches and other genomics tools to predict enzyme function.}, } @article {pmid21443626, year = {2011}, author = {Feller, A and Machemer, K and Braun, EL and Grotewold, E}, title = {Evolutionary and comparative analysis of MYB and bHLH plant transcription factors.}, journal = {The Plant journal : for cell and molecular biology}, volume = {66}, number = {1}, pages = {94-116}, doi = {10.1111/j.1365-313X.2010.04459.x}, pmid = {21443626}, issn = {1365-313X}, mesh = {Amino Acid Sequence ; Arabidopsis/genetics ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; *Evolution, Molecular ; Gene Duplication ; Gene Expression Regulation, Plant ; Gene Regulatory Networks ; *Genes, myb ; Molecular Sequence Data ; Multigene Family ; Plants/*genetics ; Proto-Oncogene Proteins c-myb/genetics ; }, abstract = {The expansion of gene families encoding regulatory proteins is typically associated with the increase in complexity characteristic of multi-cellular organisms. The MYB and basic helix-loop-helix (bHLH) families provide excellent examples of how gene duplication and divergence within particular groups of transcription factors are associated with, if not driven by, the morphological and metabolic diversity that characterize the higher plants. These gene families expanded dramatically in higher plants; for example, there are approximately 339 and 162 MYB and bHLH genes, respectively, in Arabidopsis, and approximately 230 and 111, respectively, in rice. In contrast, the Chlamydomonas genome has only 38 MYB genes and eight bHLH genes. In this review, we compare the MYB and bHLH gene families from structural, evolutionary and functional perspectives. The knowledge acquired on the role of many of these factors in Arabidopsis provides an excellent reference to explore sequence-function relationships in crops and other plants. The physical interaction and regulatory synergy between particular sub-classes of MYB and bHLH factors is perhaps one of the best examples of combinatorial plant gene regulation. However, members of the MYB and bHLH families also interact with a number of other regulatory proteins, forming complexes that either activate or repress the expression of sets of target genes that are increasingly being identified through a diversity of high-throughput genomic approaches. The next few years are likely to witness an increasing understanding of the extent to which conserved transcription factors participate at similar positions in gene regulatory networks across plant species.}, } @article {pmid21443622, year = {2011}, author = {Tirichine, L and Bowler, C}, title = {Decoding algal genomes: tracing back the history of photosynthetic life on Earth.}, journal = {The Plant journal : for cell and molecular biology}, volume = {66}, number = {1}, pages = {45-57}, doi = {10.1111/j.1365-313X.2011.04540.x}, pmid = {21443622}, issn = {1365-313X}, mesh = {*Biological Evolution ; Chlorophyta/*genetics ; Cryptophyta/genetics ; Dinoflagellida/genetics ; Epigenesis, Genetic ; *Genome, Plant ; *Photosynthesis ; Phylogeny ; Rhodophyta/genetics ; Symbiosis ; }, abstract = {The last decade has witnessed outstanding progress in sequencing the genomes of photosynthetic eukaryotes, from major cereal crops to single celled marine phytoplankton. For the algae, we now have whole genome sequences from green, red, and brown representatives, and multiple efforts based on comparative and functional genomics approaches have provided information about the unicellular origins of higher plants, and about the evolution of photosynthetic life in general. Here we present some of the highlights from such studies, including the endosymbiotic origins of photosynthetic protists and their positioning with respect to plants and animals, the evolution of multicellularity in photosynthetic lineages, the role of sex in unicellular algae, and the potential relevance of epigenetic processes in contributing to the adaptation of algae to their environment.}, } @article {pmid21440376, year = {2011}, author = {Størmer, FC and Mysterud, I and Slagsvold, T}, title = {Evolution and possible storage of information in a magnetite system of significance for brain development.}, journal = {Medical hypotheses}, volume = {76}, number = {6}, pages = {901-904}, doi = {10.1016/j.mehy.2011.03.004}, pmid = {21440376}, issn = {1532-2777}, mesh = {Bacterial Physiological Phenomena ; Biofilms ; *Biological Evolution ; Brain/*growth & development ; *Ferrosoferric Oxide ; Humans ; }, abstract = {The initial evolutionary electromagnetic steps in the history of brain development are still unknown, although such knowledge might be of high relevance in understanding human degenerative diseases. All prokaryote organisms, one-celled or multicellular, must have an inherited system to process and store information activating instincts and reflexes, in order to give a quick response to external stimuli. We argue that magnetite is an obvious compound to be evaluated as an initial precursor from prebiotic Earth history in the evolution of such a system. Magnetite is a stable ferrimagnetic compound, present in organisms ranging from bacteria to humans. It occurred naturally in the early Earth environment and was later synthesized de novo in biotic organisms. We suggest that the use of magnetite has evolved to represent the main storage system for learned memory in all organisms living today.}, } @article {pmid21439073, year = {2011}, author = {Montaño, AM and Tsujino, F and Takahata, N and Satta, Y}, title = {Evolutionary origin of peptidoglycan recognition proteins in vertebrate innate immune system.}, journal = {BMC evolutionary biology}, volume = {11}, number = {}, pages = {79}, pmid = {21439073}, issn = {1471-2148}, mesh = {Animals ; Carrier Proteins/*genetics/immunology ; *Evolution, Molecular ; Gene Duplication ; *Immunity, Innate ; Multigene Family ; Sequence Analysis, DNA ; Vertebrates/*genetics/*immunology ; }, abstract = {BACKGROUND: Innate immunity is the ancient defense system of multicellular organisms against microbial infection. The basis of this first line of defense resides in the recognition of unique motifs conserved in microorganisms, and absent in the host. Peptidoglycans, structural components of bacterial cell walls, are recognized by Peptidoglycan Recognition Proteins (PGRPs). PGRPs are present in both vertebrates and invertebrates. Although some evidence for similarities and differences in function and structure between them has been found, their evolutionary history and phylogenetic relationship have remained unclear. Such studies have been severely hampered by the great extent of sequence divergence among vertebrate and invertebrate PGRPs. Here we investigate the birth and death processes of PGRPs to elucidate their origin and diversity.

RESULTS: We found that (i) four rounds of gene duplication and a single domain duplication have generated the major variety of present vertebrate PGRPs, while in invertebrates more than ten times the number of duplications are required to explain the repertoire of present PGRPs, and (ii) the death of genes in vertebrates appears to be almost null whereas in invertebrates it is frequent.

CONCLUSION: These results suggest that the emergence of new PGRP genes may have an impact on the availability of the repertoire and its function against pathogens. These striking differences in PGRP evolution of vertebrates and invertebrates should reflect the differences in the role of their innate immunity. Insights on the origin of PGRP genes will pave the way to understand the evolution of the interaction between host and pathogens and to lead to the development of new treatments for immune diseases that involve proteins related to the recognition of self and non-self.}, } @article {pmid21439063, year = {2011}, author = {Kaczanowski, S and Sajid, M and Reece, SE}, title = {Evolution of apoptosis-like programmed cell death in unicellular protozoan parasites.}, journal = {Parasites & vectors}, volume = {4}, number = {}, pages = {44}, pmid = {21439063}, issn = {1756-3305}, support = {WT082234MA//Wellcome Trust/United Kingdom ; }, mesh = {*Apoptosis ; Computational Biology/methods ; Evolution, Molecular ; Leishmania/*physiology ; Plasmodium/*physiology ; Trypanosoma/*physiology ; }, abstract = {Apoptosis-like programmed cell death (PCD) has recently been described in multiple taxa of unicellular protists, including the protozoan parasites Plasmodium, Trypanosoma and Leishmania. Apoptosis-like PCD in protozoan parasites shares a number of morphological features with programmed cell death in multicellular organisms. However, both the evolutionary explanations and mechanisms involved in parasite PCD are poorly understood. Explaining why unicellular organisms appear to undergo 'suicide' is a challenge for evolutionary biology and uncovering death executors and pathways is a challenge for molecular and cell biology. Bioinformatics has the potential to integrate these approaches by revealing homologies in the PCD machinery of diverse taxa and evaluating their evolutionary trajectories. As the molecular mechanisms of apoptosis in model organisms are well characterised, and recent data suggest similar mechanisms operate in protozoan parasites, key questions can now be addressed. These questions include: which elements of apoptosis machinery appear to be shared between protozoan parasites and multicellular taxa and, have these mechanisms arisen through convergent or divergent evolution? We use bioinformatics to address these questions and our analyses suggest that apoptosis mechanisms in protozoan parasites and other taxa have diverged during their evolution, that some apoptosis factors are shared across taxa whilst others have been replaced by proteins with similar biochemical activities.}, } @article {pmid21427965, year = {2010}, author = {Natochin, IuV}, title = {[From quantum to integrative physiology].}, journal = {Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova}, volume = {96}, number = {11}, pages = {1043-1061}, pmid = {21427965}, issn = {0869-8139}, mesh = {Animals ; Autacoids/physiology ; Genome ; Humans ; *Molecular Biology ; *Physiological Phenomena ; *Quantum Theory ; }, abstract = {Physiology studies the functions of different organs, systems and how they maintain the integrity of organisms. Nervous and endocrine systems react to stimulus, causality plays a key role in their activities. Physical and chemical conditions of fluids in the internal environment serve as a background and an active modulator for regulatory influences. Autacoid formation is in many respects based on probable events. It has been proved, that during the formation of regulatory systems in cell evolution the appearance of regulatory molecules was based on statistical probability of quantum events: sporadical appearance in cells during metabolism of peptides, lipids, hydrolysis of larger molecules on fragments, quanta, which received physiological activity in the form of function regulators. These processes in their adapted, according to Darwin's mechanism of natural selection, value were recorded into the genome since synthesis readings of the polypeptides were fixed. The formation of multicellular organisms was promoted by the arise of regulatory systems and their integration under the supervision of the nervous system.}, } @article {pmid21424025, year = {2011}, author = {Mian, IS and Rose, C}, title = {Communication theory and multicellular biology.}, journal = {Integrative biology : quantitative biosciences from nano to macro}, volume = {3}, number = {4}, pages = {350-367}, doi = {10.1039/c0ib00117a}, pmid = {21424025}, issn = {1757-9708}, mesh = {Aging/physiology ; Algorithms ; Animals ; *Biological Evolution ; Body Patterning/physiology ; Cell Communication/*physiology ; Chemotaxis/physiology ; Chromosomes/physiology ; Dictyosteliida/physiology ; Female ; Genetic Code/physiology ; Genetic Phenomena/physiology ; Growth and Development/physiology ; Humans ; *Information Theory ; Mammary Glands, Animal/growth & development ; Pheromones/metabolism ; Polysaccharides/physiology ; Quorum Sensing/physiology ; Saccharomyces cerevisiae/physiology ; Signal Transduction/physiology ; Spindle Apparatus/physiology ; }, abstract = {In this Perspective, we propose that communication theory--a field of mathematics concerned with the problems of signal transmission, reception and processing--provides a new quantitative lens for investigating multicellular biology, ancient and modern. What underpins the cohesive organisation and collective behaviour of multicellular ecosystems such as microbial colonies and communities (microbiomes) and multicellular organisms such as plants and animals, whether built of simple tissue layers (sponges) or of complex differentiated cells arranged in tissues and organs (members of the 35 or so phyla of the subkingdom Metazoa)? How do mammalian tissues and organs develop, maintain their architecture, become subverted in disease, and decline with age? How did single-celled organisms coalesce to produce many-celled forms that evolved and diversified into the varied multicellular organisms in existence today? Some answers can be found in the blueprints or recipes encoded in (epi)genomes, yet others lie in the generic physical properties of biological matter such as the ability of cell aggregates to attain a certain complexity in size, shape, and pattern. We suggest that Lasswell's maxim "Who says what to whom in what channel with what effect" provides a foundation for understanding not only the emergence and evolution of multicellularity, but also the assembly and sculpting of multicellular ecosystems and many-celled structures, whether of natural or human-engineered origin. We explore how the abstraction of communication theory as an organising principle for multicellular biology could be realised. We highlight the inherent ability of communication theory to be blind to molecular and/or genetic mechanisms. We describe selected applications that analyse the physics of communication and use energy efficiency as a central tenet. Whilst communication theory has and could contribute to understanding a myriad of problems in biology, investigations of multicellular biology could, in turn, lead to advances in communication theory, especially in the still immature field of network information theory.}, } @article {pmid21419156, year = {2011}, author = {Gerlee, P and Basanta, D and Anderson, AR}, title = {Evolving homeostatic tissue using genetic algorithms.}, journal = {Progress in biophysics and molecular biology}, volume = {106}, number = {2}, pages = {414-425}, pmid = {21419156}, issn = {1873-1732}, support = {U54 CA113007/CA/NCI NIH HHS/United States ; 5U54 CA113007/CA/NCI NIH HHS/United States ; }, mesh = {*Algorithms ; Biological Evolution ; Cell Communication/*physiology ; Cellular Microenvironment/*physiology ; Evolution, Molecular ; Homeostasis/*physiology ; Humans ; Models, Biological ; Morphogenesis/physiology ; Mutation/genetics ; Neoplasms/physiopathology ; Signal Transduction/physiology ; Wounds and Injuries/physiopathology ; }, abstract = {Multicellular organisms maintain form and function through a multitude of homeostatic mechanisms. The details of these mechanisms are in many cases unknown, and so are their evolutionary origin and their link to development. In order to illuminate these issues we have investigated the evolution of structural homeostasis in the simplest of cases, a tissue formed by a mono-layer of cells. To this end, we made use of a 3-dimensional hybrid cellular automaton, an individual-based model in which the behaviour of each cell depends on its local environment. Using an evolutionary algorithm (EA) we evolved cell signalling networks, both with a fixed and an incremental fitness evaluation, which give rise to and maintain a mono-layer tissue structure. Analysis of the solutions provided by the EA shows that the two evaluation methods gives rise to different types of solutions to the problem of homeostasis. The fixed method leads to almost optimal solutions, where the tissue relies on a high rate of cell turnover, while the solutions from the incremental scheme behave in a more conservative manner, only dividing when necessary. In order to test the robustness of the solutions we subjected them to environmental stress, by wounding the tissue, and to genetic stress, by introducing mutations. The results show that the robustness very much depends on the mechanism responsible for maintaining homeostasis. The two evolved cell types analysed present contrasting mechanisms by which tissue homeostasis can be maintained. This compares well to different tissue types found in multicellular organisms. For example the epithelial cells lining the colon in humans are shed at a considerable rate, while in other tissue types, which are not as exposed, the conservative type of homeostatic mechanism is normally found. These results will hopefully shed light on how multicellular organisms have evolved homeostatic mechanisms and what might occur when these mechanisms fail, as in the case of cancer.}, } @article {pmid21415026, year = {2011}, author = {Hilman, D and Gat, U}, title = {The evolutionary history of YAP and the hippo/YAP pathway.}, journal = {Molecular biology and evolution}, volume = {28}, number = {8}, pages = {2403-2417}, doi = {10.1093/molbev/msr065}, pmid = {21415026}, issn = {1537-1719}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Base Sequence ; *Evolution, Molecular ; Gene Order ; Humans ; Intracellular Signaling Peptides and Proteins/chemistry/classification/*genetics ; Introns/genetics ; Molecular Sequence Data ; Molecular Structure ; Phylogeny ; Protein Binding ; Sequence Alignment ; Signal Transduction/*genetics ; Transcription Factors/chemistry/classification/*genetics ; }, abstract = {The Hippo/YAP pathway plays an important role in animal organ size control, which it exerts by regulating tissue proliferation and apoptosis rates as a response to developmental cues, cell contact, and density. With the ever increasing advance in genome sequencing and analysis tools, our understanding of the animal world and its evolution has greatly increased in the recent years. We used bioinformatic tools to study the evolution of the Hippo/YAP pathway focusing on the transcriptional coactivator YAP, which is a pivotal effector of the pathway. The aim was to establish the origin and mode of development of YAP and its pathway in the animal world. Some pathway members can be already identified in single-celled eukaryotes like the yeast that have preceded multicellular animals. Interestingly, we can find most of the components that are present in human in the sea-anemone Nematostella, which belongs to a very basal group of metazoans, the cnidarians. All the major domains of YAP have been conserved between cnidarians and mammals, and YAP can be identified even in the more basal placozoan clade. We show a very high degree of conservation in regions such as the WW and the TEAD-binding domains, TEAD being the major DNA-binding partner of YAP. Remarkably, we found that the location of an intron in the WW1 genomic region has been invariant along an evolutionary span of over 700 My. We have followed the evolutionary changes in YAP and in other main components of the pathway from the first metazoans such as sponges, described the phylogenetic relationships between the YAP genes and indicated where YAP and other components have been secondarily lost. Evidence is provided that YAP and its binding partner TEAD demonstrate strong coevolution. This gives further support for the importance of the TEAD-YAP association. Beyond contributing to an understanding of the evolutionary history of this pathway, we have provided insights into the "birth" of this pathway, its functions and its mode of operation in animals with different body plans, development, and life styles.}, } @article {pmid21402861, year = {2011}, author = {Roch, GJ and Sherwood, NM}, title = {Stanniocalcin has deep evolutionary roots in eukaryotes.}, journal = {Genome biology and evolution}, volume = {3}, number = {}, pages = {284-294}, pmid = {21402861}, issn = {1759-6653}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Conserved Sequence/genetics ; Cysteine/genetics ; Eukaryotic Cells/*metabolism ; *Evolution, Molecular ; Glycoproteins/chemistry/*genetics ; Humans ; Molecular Sequence Data ; Peptides/chemistry ; Phylogeny ; Sequence Alignment ; Sequence Homology, Amino Acid ; Species Specificity ; }, abstract = {Vertebrates have a large glycoprotein hormone, stanniocalcin, which originally was shown to inhibit calcium uptake from the environment in teleost fish gills. Later, humans, other mammals, and teleost fish were shown to have two forms of stanniocalcin (STC1 and STC2) that were widely distributed in many tissues. STC1 is associated with calcium and phosphate homeostasis and STC2 with phosphate, but their receptors and signaling pathways have not been elucidated. We undertook a phylogenetic investigation of stanniocalcin beyond the vertebrates using a combination of BLAST and HMMER homology searches in protein, genomic, and expressed sequence tag databases. We identified novel STC homologs in a diverse array of multicellular and unicellular organisms. Within the eukaryotes, almost all major taxonomic groups except plants and algae have STC homologs, although some groups like echinoderms and arthropods lack STC genes. The critical structural feature for recognition of stanniocalcins was the conserved pattern of ten cysteines, even though the amino acid sequence identity was low. Signal peptides in STC sequences suggest they are secreted from the cell of synthesis. The role of glycosylation signals and additional cysteines is not yet clear, although the 11th cysteine, if present, has been shown to form homodimers in some vertebrates. We predict that large secreted stanniocalcin homologs appeared in evolution as early as single-celled eukaryotes. Stanniocalcin's tertiary structure with five disulfide bonds and its primary structure with modest amino acid conservation currently lack an established receptor-signaling system, although we suggest possible alternatives.}, } @article {pmid21399765, year = {2011}, author = {Antunes, LC and Davies, JE and Finlay, BB}, title = {Chemical signaling in the gastrointestinal tract.}, journal = {F1000 biology reports}, volume = {3}, number = {}, pages = {4}, pmid = {21399765}, issn = {1757-594X}, abstract = {Chemical signaling via the production of small molecules such as hormones has been studied in detail in higher organisms. These molecules have important functions in maintaining physiological homeostasis as well as allowing organisms to respond to external insults. Virtually every living cell produces hormone-like diffusible small molecules that can be used to convey messages to neighboring cells-a vital step in adaptation, development, and survival within populations. Although most of our knowledge on cellular chemical communication comes from studies of multicellular eukaryotes, it is now understood that bacteria can also communicate using sophisticated signaling systems, in a way analogous to those used by higher organisms. Many of these microbes live in close association with higher eukaryotes, in mutualistic or commensal relationships. We suggest that there may be a wealth of unidentified bioactive small molecules in the human body, originating from both microbial and human cells and that have important biological functions. Because chemical signaling has important roles for the biology of both microbes and humans, detecting, identifying, and studying these chemical signals can further our understanding of the chemical interplay between microbiota and their hosts and provide us with an unexplored source of molecules that could be used for human benefit.}, } @article {pmid21396932, year = {2011}, author = {Sugden, C and Ross, S and Annesley, SJ and Cole, C and Bloomfield, G and Ivens, A and Skelton, J and Fisher, PR and Barton, G and Williams, JG}, title = {A Dictyostelium SH2 adaptor protein required for correct DIF-1 signaling and pattern formation.}, journal = {Developmental biology}, volume = {353}, number = {2}, pages = {290-301}, pmid = {21396932}, issn = {1095-564X}, support = {MC_U105115237/MRC_/Medical Research Council/United Kingdom ; MR/K001744/1/MRC_/Medical Research Council/United Kingdom ; 053640/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Base Sequence ; DNA Primers/genetics ; DNA, Protozoan/genetics ; Darkness ; Dictyostelium/genetics/*growth & development/*metabolism ; Extracellular Matrix Proteins/genetics/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genes, Protozoan ; Hexanones/*metabolism ; Light ; Metalloendopeptidases/genetics/metabolism ; Mutation ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Protozoan Proteins/genetics/*metabolism ; Signal Transduction ; src Homology Domains ; }, abstract = {Dictyostelium is the only non-metazoan with functionally analyzed SH2 domains and studying them can give insights into their evolution and wider potential. LrrB has a novel domain configuration with leucine-rich repeat, 14-3-3 and SH2 protein-protein interaction modules. It is required for the correct expression of several specific genes in early development and here we characterize its role in later, multicellular development. During development in the light, slug formation in LrrB null (lrrB-) mutants is delayed relative to the parental strain, and the slugs are highly defective in phototaxis and thermotaxis. In the dark the mutant arrests development as an elongated mound, in a hitherto unreported process we term dark stalling. The developmental and phototaxis defects are cell autonomous and marker analysis shows that the pstO prestalk sub-region of the slug is aberrant in the lrrB- mutant. Expression profiling, by parallel micro-array and deep RNA sequence analyses, reveals many other alterations in prestalk-specific gene expression in lrrB- slugs, including reduced expression of the ecmB gene and elevated expression of ampA. During culmination ampA is ectopically expressed in the stalk, there is no expression of ampA and ecmB in the lower cup and the mutant fruiting bodies lack a basal disc. The basal disc cup derives from the pstB cells and this population is greatly reduced in the lrrB- mutant. This anatomical feature is a hallmark of mutants aberrant in signaling by DIF-1, the polyketide that induces prestalk and stalk cell differentiation. In a DIF-1 induction assay the lrrB- mutant is profoundly defective in ecmB activation but only marginally defective in ecmA induction. Thus the mutation partially uncouples these two inductive events. In early development LrrB interacts physically and functionally with CldA, another SH2 domain containing protein. However, the CldA null mutant does not phenocopy the lrrB- in its aberrant multicellular development or phototaxis defect, implying that the early and late functions of LrrB are affected in different ways. These observations, coupled with its domain structure, suggest that LrrB is an SH2 adaptor protein active in diverse developmental signaling pathways.}, } @article {pmid21395443, year = {2011}, author = {Sala, FG and Matthews, JA and Speer, AL and Torashima, Y and Barthel, ER and Grikscheit, TC}, title = {A multicellular approach forms a significant amount of tissue-engineered small intestine in the mouse.}, journal = {Tissue engineering. Part A}, volume = {17}, number = {13-14}, pages = {1841-1850}, pmid = {21395443}, issn = {1937-335X}, mesh = {Animals ; Cell Count ; Cell Differentiation ; Cell Lineage ; Epithelial Cells/cytology/metabolism ; Green Fluorescent Proteins/metabolism ; Humans ; Implants, Experimental ; Intestinal Mucosa/cytology ; Intestine, Small/cytology/innervation/*physiology ; Mesoderm/cytology/metabolism ; Mice ; Mice, Transgenic ; Models, Animal ; Organoids/*cytology ; Rats ; Stem Cell Niche/cytology ; Time Factors ; Tissue Engineering/*methods ; }, abstract = {Tissue-engineered small intestine (TESI) has successfully been used to rescue Lewis rats after massive small bowel resection. In this study, we transitioned the technique to a mouse model, allowing investigation of the processes involved during TESI formation through the transgenic tools available in this species. This is a necessary step toward applying the technique to human therapy. Multicellular organoid units were derived from small intestines of transgenic mice and transplanted within the abdomen on biodegradable polymers. Immunofluorescence staining was used to characterize the cellular processes during TESI formation. We demonstrate the preservation of Lgr5- and DcamKl1-positive cells, two putative intestinal stem cell populations, in proximity to their niche mesenchymal cells, the intestinal subepithelial myofibroblasts (ISEMFs), at the time of implantation. Maintenance of the relationship between ISEMF and crypt epithelium is observed during the growth of TESI. The engineered small intestine has an epithelium containing a differentiated epithelium next to an innervated muscularis. Lineage tracing demonstrates that all the essential components, including epithelium, muscularis, nerves, and some of the blood vessels, are of donor origin. This multicellular approach provides the necessary cell population to regenerate large amounts of intestinal tissue that could be used to treat short bowel syndrome.}, } @article {pmid21393547, year = {2011}, author = {Dickinson, DJ and Nelson, WJ and Weis, WI}, title = {A polarized epithelium organized by beta- and alpha-catenin predates cadherin and metazoan origins.}, journal = {Science (New York, N.Y.)}, volume = {331}, number = {6022}, pages = {1336-1339}, pmid = {21393547}, issn = {1095-9203}, support = {R01 GM035527/GM/NIGMS NIH HHS/United States ; R01 GM056169-15/GM/NIGMS NIH HHS/United States ; R37 GM035527/GM/NIGMS NIH HHS/United States ; GM035527/GM/NIGMS NIH HHS/United States ; R01 GM056169/GM/NIGMS NIH HHS/United States ; GM56169/GM/NIGMS NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/metabolism ; Cadherins/metabolism ; *Cell Polarity ; Cellulose/metabolism ; Dictyostelium/cytology/growth & development/*physiology/ultrastructure ; Epithelial Cells/*physiology/ultrastructure ; Epithelium/*physiology ; Intercellular Junctions/metabolism ; Morphogenesis ; Protozoan Proteins/chemistry/genetics/*metabolism ; RNA Interference ; alpha Catenin/chemistry/genetics/*metabolism ; beta Catenin/*metabolism ; }, abstract = {A fundamental characteristic of metazoans is the formation of a simple, polarized epithelium. In higher animals, the structural integrity and functional polarization of simple epithelia require a cell-cell adhesion complex that contains a classical cadherin, the Wnt-signaling protein β-catenin and the actin-binding protein α-catenin. We show that the non-metazoan Dictyostelium discoideum forms a polarized epithelium that is essential for multicellular development. Although D. discoideum lacks a cadherin homolog, we identify an α-catenin ortholog that binds a β-catenin-related protein. Both proteins are essential for formation of the epithelium, polarized protein secretion, and proper multicellular morphogenesis. Thus, the organizational principles of metazoan multicellularity may be more ancient than previously recognized, and the role of the catenins in cell polarity predates the evolution of Wnt signaling and classical cadherins.}, } @article {pmid21385054, year = {2011}, author = {Takahashi, Y and Daitoku, H and Yokoyama, A and Nakayama, K and Kim, JD and Fukamizu, A}, title = {The C. elegans PRMT-3 possesses a type III protein arginine methyltransferase activity.}, journal = {Journal of receptor and signal transduction research}, volume = {31}, number = {2}, pages = {168-172}, doi = {10.3109/10799893.2011.555768}, pmid = {21385054}, issn = {1532-4281}, mesh = {Animals ; Biocatalysis ; Caenorhabditis elegans/*enzymology ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Histones/metabolism ; Humans ; Methylation ; Methyltransferases/chemistry ; Phylogeny ; Protein Binding ; Protein-Arginine N-Methyltransferases/genetics/*metabolism ; S-Adenosylmethionine/metabolism ; Sequence Homology, Amino Acid ; omega-N-Methylarginine/metabolism ; }, abstract = {Protein arginine methylation is a common post-translational modification in eukaryotes that is catalyzed by a family of the protein arginine methyltransferases (PRMTs). PRMTs are classified into three types: type I and type II add asymmetrically and symmetrically dimethyl groups to arginine, respectively, while type III adds solely monomethyl group to arginine. However, although the enzymatic activity of type I and type II PRMTs have been reported, the substrate specificity and the methylation activity of type III PRMTs still remains unknown. Here, we report the characterization of Caenorhabditis elegans PRMT-2 and PRMT-3, both of which are highly homologous to human PRMT7. We find that these two PRMTs can bind to S-adenosyl methionine (SAM), but only PRMT-3 has methyltransferase activity for histone H2A depending on its SAM-binding domain. Importantly, thin-layer chromatographic analysis demonstrates that PRMT-3 catalyzes the formation of monomethylated, but not dimethylated arginine. Our study thus identifies the first type III PRMT in C. elegans and provides a means to elucidate the physiological significance of arginine monomethylation in multicellular organisms.}, } @article {pmid21382633, year = {2011}, author = {Otterholt, E and Charnock, C}, title = {Identification and phylogeny of the small eukaryote population of raw and drinking waters.}, journal = {Water research}, volume = {45}, number = {8}, pages = {2527-2538}, doi = {10.1016/j.watres.2011.02.008}, pmid = {21382633}, issn = {1879-2448}, mesh = {Acanthamoeba castellanii/classification/genetics/isolation & purification ; Base Sequence ; Biodiversity ; Eukaryota/*classification/genetics/isolation & purification ; Fresh Water/*parasitology ; Molecular Sequence Data ; Norway ; *Phylogeny ; Water Supply/*analysis ; }, abstract = {Culture-dependent and -independent methods were used to investigate the small eukaryote composition of raw and finished waters in the Norwegian cities of Oslo, Tromsø, Fredrikstad and Oppegård. Probes with general applicability to the 18S rRNA genes of the small eukaryote consortium were used for PCR-denaturing gradient gel electrophoresis (DGGE), and in the generation of clone libraries using the TOPO™ cloning and sequencing system. The chosen probes invariably gave a single band in agarose gel electrophoresis, indicating amplification of an area of similar size. DGGE and cloning analyses resolved the bands into components representing many unique amplicons. Diversity and composition in the collection were studied by DNA-sequencing, and visual examination of DGGE patterns. The cloning approach enabled the putative identification of a total of approximately 100 unique small eukaryotes. The major fraction of these represented ciliated and flagellated protozoal species. This was in keeping with the findings from protozoal cultivation. DNA from a number of multicellular eukaryotes was also detected. Amoebal and fungal DNA was rarely found. The latter may indicate a low incidence or a bias in the analysis technique. The population of small eukaryotes appears typical for pristine waters and no primary pathogens were detected by culture-independent techniques. However, the potentially pathogenic protozoa Acanthamoeba castellanii was grown on one occasion from Oslo's drinking water. DGGE allowed the identification of fewer amplicons (by excision and sequencing of bands) than by the cloning-transformation approach. The DGGE analysis revealed clear similarities between the compositions of the raw and treated waters, indicating that cells or DNA in the raw water pass through the treatment trains. Protozoal culture and heterotrophic plate count analysis consistently revealed viable cells in both raw and treated waters in Oslo. This indicates that a fraction of the clone library represents eukaryotic species surviving the treatment trains. The analyses here presented represent the first published study of the general small eukaryotic fraction of the Capital's drinking water, and those of three other Norwegian cities. We suggest that DGGE profiles may have a value in judging physical treatment efficacy (removal of cells), but that direct cloning and sequencing studies is more amenable for characterization of uncultured microbes.}, } @article {pmid21373189, year = {2011}, author = {Vandenborre, G and Smagghe, G and Ghesquière, B and Menschaert, G and Nagender Rao, R and Gevaert, K and Van Damme, EJ}, title = {Diversity in protein glycosylation among insect species.}, journal = {PloS one}, volume = {6}, number = {2}, pages = {e16682}, pmid = {21373189}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Bees/chemistry/metabolism ; Chromatography, Affinity ; Drosophila melanogaster/chemistry/metabolism ; Glycoproteins/analysis/chemistry/isolation & purification/*metabolism ; Glycosylation ; Insect Proteins/analysis/chemistry/isolation & purification/*metabolism ; Insecta/*metabolism ; Mannose-Binding Lectins/metabolism ; Metabolome ; Molecular Sequence Data ; Phylogeny ; Plant Lectins/metabolism ; Protein Binding ; *Protein Processing, Post-Translational/physiology ; Species Specificity ; Tribolium/chemistry/metabolism ; }, abstract = {BACKGROUND: A very common protein modification in multicellular organisms is protein glycosylation or the addition of carbohydrate structures to the peptide backbone. Although the Class of the Insecta is the largest animal taxon on Earth, almost all information concerning glycosylation in insects is derived from studies with only one species, namely the fruit fly Drosophila melanogaster.

In this report, the differences in glycoproteomes between insects belonging to several economically important insect orders were studied. Using GNA (Galanthus nivalis agglutinin) affinity chromatography, different sets of glycoproteins with mannosyl-containing glycan structures were purified from the flour beetle (Tribolium castaneum), the silkworm (Bombyx mori), the honeybee (Apis mellifera), the fruit fly (D. melanogaster) and the pea aphid (Acyrthosiphon pisum). To identify and characterize the purified glycoproteins, LC-MS/MS analysis was performed. For all insect species, it was demonstrated that glycoproteins were related to a broad range of biological processes and molecular functions. Moreover, the majority of glycoproteins retained on the GNA column were unique to one particular insect species and only a few glycoproteins were present in the five different glycoprotein sets. Furthermore, these data support the hypothesis that insect glycoproteins can be decorated with mannosylated O-glycans.

CONCLUSIONS/SIGNIFICANCE: The results presented here demonstrate that oligomannose N-glycosylation events are highly specific depending on the insect species. In addition, we also demonstrated that protein O-mannosylation in insect species may occur more frequently than currently believed.}, } @article {pmid21371934, year = {2012}, author = {Asghar, A and Groth, M and Siol, O and Gaube, F and Enzensperger, C and Glöckner, G and Winckler, T}, title = {Developmental gene regulation by an ancient intercellular communication system in social amoebae.}, journal = {Protist}, volume = {163}, number = {1}, pages = {25-37}, doi = {10.1016/j.protis.2010.12.002}, pmid = {21371934}, issn = {1618-0941}, mesh = {Amoebozoa/classification/genetics/*growth & development/*physiology ; Biological Evolution ; *Cell Communication ; Dipeptides/metabolism ; *Gene Expression Regulation, Developmental ; Lactams/metabolism ; Molecular Sequence Data ; Phylogeny ; Protozoan Proteins/*genetics/metabolism ; }, abstract = {The social amoebae (Dictyostelia) use quorum sensing-like communication systems to coordinate the periodic transition from uni- to multicellularity. The monophyletic descent of the Dictyostelia provides a unique opportunity to study the origin and adaptive evolution of such intercellular communication systems. We determined that the ability of aggregation-competent cells to respond to the intercellular messenger glorin occurred in the most ancient taxa of the Dictyostelia. We show using Illumina sequencing technology that glorin mediates rapid changes in gene expression at the transition from vegetative growth to aggregation. We conclude that peptide-based communication is the most ancient form of intercellular signaling in the evolution of multicellularity in the social amoebae, but has been repeatedly replaced by other communication systems during the monophyletic evolution of the social amoebae. Glorin communication has parallels with quorum sensing in that the molecule diffuses into the field, stimulates gene expression in receptive cells and coordinates a population-wide response.}, } @article {pmid21367778, year = {2011}, author = {Solari, CA and Drescher, K and Ganguly, S and Kessler, JO and Michod, RE and Goldstein, RE}, title = {Flagellar phenotypic plasticity in volvocalean algae correlates with Péclet number.}, journal = {Journal of the Royal Society, Interface}, volume = {8}, number = {63}, pages = {1409-1417}, pmid = {21367778}, issn = {1742-5662}, support = {BB/F021844/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Biological Evolution ; Cell Size ; Chlorophyta/*cytology/*physiology ; Flagella/physiology ; }, abstract = {Flagella-generated fluid stirring has been suggested to enhance nutrient uptake for sufficiently large micro-organisms, and to have played a role in evolutionary transitions to multicellularity. A corollary to this predicted size-dependent benefit is a propensity for phenotypic plasticity in the flow-generating mechanism to appear in large species under nutrient deprivation. We examined four species of volvocalean algae whose radii and flow speeds differ greatly, with Péclet numbers (Pe) separated by several orders of magnitude. Populations of unicellular Chlamydomonas reinhardtii and one- to eight-celled Gonium pectorale (Pe ∼ 0.1-1) and multicellular Volvox carteri and Volvox barberi (Pe ∼ 100) were grown in diluted and undiluted media. For C. reinhardtii and G. pectorale, decreasing the nutrient concentration resulted in smaller cells, but had no effect on flagellar length and propulsion force. In contrast, these conditions induced Volvox colonies to grow larger and increase their flagellar length, separating the somatic cells further. Detailed studies on V. carteri found that the opposing effects of increasing beating force and flagellar spacing balance, so the fluid speed across the colony surface remains unchanged between nutrient conditions. These results lend further support to the hypothesized link between the Péclet number, nutrient uptake and the evolution of biological complexity in the Volvocales.}, } @article {pmid21356102, year = {2011}, author = {Sucgang, R and Kuo, A and Tian, X and Salerno, W and Parikh, A and Feasley, CL and Dalin, E and Tu, H and Huang, E and Barry, K and Lindquist, E and Shapiro, H and Bruce, D and Schmutz, J and Salamov, A and Fey, P and Gaudet, P and Anjard, C and Babu, MM and Basu, S and Bushmanova, Y and van der Wel, H and Katoh-Kurasawa, M and Dinh, C and Coutinho, PM and Saito, T and Elias, M and Schaap, P and Kay, RR and Henrissat, B and Eichinger, L and Rivero, F and Putnam, NH and West, CM and Loomis, WF and Chisholm, RL and Shaulsky, G and Strassmann, JE and Queller, DC and Kuspa, A and Grigoriev, IV}, title = {Comparative genomics of the social amoebae Dictyostelium discoideum and Dictyostelium purpureum.}, journal = {Genome biology}, volume = {12}, number = {2}, pages = {R20}, pmid = {21356102}, issn = {1474-760X}, support = {HG0022/HG/NHGRI NIH HHS/United States ; MC_U105115237/MRC_/Medical Research Council/United Kingdom ; HD39691/HD/NICHD NIH HHS/United States ; R01 GM087371/GM/NIGMS NIH HHS/United States ; MC_U105185859/MRC_/Medical Research Council/United Kingdom ; 1 T90 DA022885/DA/NIDA NIH HHS/United States ; BB/D013453/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 1 R90 DA023418/DA/NIDA NIH HHS/United States ; R01 GM064426-10/GM/NIGMS NIH HHS/United States ; R01 GM087371-04/GM/NIGMS NIH HHS/United States ; R01 GM064426/GM/NIGMS NIH HHS/United States ; BB/E016308/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; P01 HD039691/HD/NICHD NIH HHS/United States ; GM84383/GM/NIGMS NIH HHS/United States ; GM64426/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; *Biological Evolution ; Conserved Sequence/genetics ; Dictyostelium/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Genetic Speciation ; *Genome ; Genome Size ; Genomics/*methods ; Histidine Kinase ; Humans ; Microsatellite Repeats ; Molecular Sequence Data ; Phylogeny ; Polyketide Synthases/genetics ; Protein Kinases/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {BACKGROUND: The social amoebae (Dictyostelia) are a diverse group of Amoebozoa that achieve multicellularity by aggregation and undergo morphogenesis into fruiting bodies with terminally differentiated spores and stalk cells. There are four groups of dictyostelids, with the most derived being a group that contains the model species Dictyostelium discoideum.

RESULTS: We have produced a draft genome sequence of another group dictyostelid, Dictyostelium purpureum, and compare it to the D. discoideum genome. The assembly (8.41 × coverage) comprises 799 scaffolds totaling 33.0 Mb, comparable to the D. discoideum genome size. Sequence comparisons suggest that these two dictyostelids shared a common ancestor approximately 400 million years ago. In spite of this divergence, most orthologs reside in small clusters of conserved synteny. Comparative analyses revealed a core set of orthologous genes that illuminate dictyostelid physiology, as well as differences in gene family content. Interesting patterns of gene conservation and divergence are also evident, suggesting function differences; some protein families, such as the histidine kinases, have undergone little functional change, whereas others, such as the polyketide synthases, have undergone extensive diversification. The abundant amino acid homopolymers encoded in both genomes are generally not found in homologous positions within proteins, so they are unlikely to derive from ancestral DNA triplet repeats. Genes involved in the social stage evolved more rapidly than others, consistent with either relaxed selection or accelerated evolution due to social conflict.

CONCLUSIONS: The findings from this new genome sequence and comparative analysis shed light on the biology and evolution of the Dictyostelia.}, } @article {pmid21355009, year = {2011}, author = {Steinmacher, DA and Guerra, MP and Saare-Surminski, K and Lieberei, R}, title = {A temporary immersion system improves in vitro regeneration of peach palm through secondary somatic embryogenesis.}, journal = {Annals of botany}, volume = {108}, number = {8}, pages = {1463-1475}, pmid = {21355009}, issn = {1095-8290}, mesh = {Arecaceae/anatomy & histology/*embryology ; Culture Media ; Hawaii ; Herbicides ; Immersion ; Picloram ; Plant Growth Regulators ; Plant Somatic Embryogenesis Techniques/methods ; Seeds/*growth & development/ultrastructure ; }, abstract = {BACKGROUND AND AIMS: Secondary somatic embryogenesis has been postulated to occur during induction of peach palm somatic embryogenesis. In the present study this morphogenetic pathway is described and a protocol for the establishment of cycling cultures using a temporary immersion system (TIS) is presented.

METHODS: Zygotic embryos were used as explants, and induction of somatic embryogenesis and plantlet growth were compared in TIS and solid culture medium. Light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to describe in vitro morphogenesis and accompany morpho-histological alterations during culture.

KEY RESULTS: The development of secondary somatic embryos occurs early during the induction of primary somatic embryos. Secondary somatic embryos were observed to develop continually in culture, resulting in non-synchronized development of these somatic embryos. Using these somatic embryos as explants allowed development of cycling cultures. Somatic embryos had high embryogenic potential (65·8 ± 3·0 to 86·2 ± 5·0 %) over the period tested. The use of a TIS greatly improved the number of somatic embryos obtained, as well as subsequent plantlet growth. Histological analyses showed that starch accumulation precedes the development of somatic embryos, and that these cells presented high nucleus/cytoplasm ratios and high mitotic indices, as evidenced by DAPI staining. Morphological and SEM observations revealed clusters of somatic embryos on one part of the explants, while other parts grew further, resulting in callus tissue. A multicellular origin of the secondary somatic embryos is hypothesized. Cells in the vicinity of callus accumulated large amounts of phenolic substances in their vacuoles. TEM revealed that these cells are metabolically very active, with the presence of numerous mitochondria and Golgi apparatuses. Light microscopy and TEM of the embryogenic sector revealed cells with numerous amyloplasts, large nuclei and nucleoli, and numerous plasmodesmata. Plantlets were obtained and after 3 months in culture their growth was significantly better in TIS than on solid culture medium. However, during acclimatization the survival rate of TIS-grown plantlets was lower.

CONCLUSIONS: The present study confirms the occurrence of secondary somatic embryos in peach palm and describes a feasible protocol for regeneration of peach palm in vitro. Further optimizations include the use of explants obtained from adult palms and improvement of somatic embryo conversion rates.}, } @article {pmid21351878, year = {2011}, author = {Popper, ZA and Michel, G and Hervé, C and Domozych, DS and Willats, WG and Tuohy, MG and Kloareg, B and Stengel, DB}, title = {Evolution and diversity of plant cell walls: from algae to flowering plants.}, journal = {Annual review of plant biology}, volume = {62}, number = {}, pages = {567-590}, doi = {10.1146/annurev-arplant-042110-103809}, pmid = {21351878}, issn = {1545-2123}, mesh = {*Biological Evolution ; Cell Communication ; Cell Wall/*physiology/ultrastructure ; Chlorophyta/physiology/ultrastructure ; Immunity, Innate ; Phaeophyta/physiology/ultrastructure ; Phylogeny ; Plant Proteins/metabolism/physiology ; Plants/*ultrastructure ; Rhodophyta/physiology/ultrastructure ; }, abstract = {All photosynthetic multicellular Eukaryotes, including land plants and algae, have cells that are surrounded by a dynamic, complex, carbohydrate-rich cell wall. The cell wall exerts considerable biological and biomechanical control over individual cells and organisms, thus playing a key role in their environmental interactions. This has resulted in compositional variation that is dependent on developmental stage, cell type, and season. Further variation is evident that has a phylogenetic basis. Plants and algae have a complex phylogenetic history, including acquisition of genes responsible for carbohydrate synthesis and modification through a series of primary (leading to red algae, green algae, and land plants) and secondary (generating brown algae, diatoms, and dinoflagellates) endosymbiotic events. Therefore, organisms that have the shared features of photosynthesis and possession of a cell wall do not form a monophyletic group. Yet they contain some common wall components that can be explained increasingly by genetic and biochemical evidence.}, } @article {pmid24710297, year = {2011}, author = {Nasir, A and Naeem, A and Khan, MJ and Nicora, HD and Caetano-Anollés, G}, title = {Annotation of Protein Domains Reveals Remarkable Conservation in the Functional Make up of Proteomes Across Superkingdoms.}, journal = {Genes}, volume = {2}, number = {4}, pages = {869-911}, pmid = {24710297}, issn = {2073-4425}, abstract = {The functional repertoire of a cell is largely embodied in its proteome, the collection of proteins encoded in the genome of an organism. The molecular functions of proteins are the direct consequence of their structure and structure can be inferred from sequence using hidden Markov models of structural recognition. Here we analyze the functional annotation of protein domain structures in almost a thousand sequenced genomes, exploring the functional and structural diversity of proteomes. We find there is a remarkable conservation in the distribution of domains with respect to the molecular functions they perform in the three superkingdoms of life. In general, most of the protein repertoire is spent in functions related to metabolic processes but there are significant differences in the usage of domains for regulatory and extra-cellular processes both within and between superkingdoms. Our results support the hypotheses that the proteomes of superkingdom Eukarya evolved via genome expansion mechanisms that were directed towards innovating new domain architectures for regulatory and extra/intracellular process functions needed for example to maintain the integrity of multicellular structure or to interact with environmental biotic and abiotic factors (e.g., cell signaling and adhesion, immune responses, and toxin production). Proteomes of microbial superkingdoms Archaea and Bacteria retained fewer numbers of domains and maintained simple and smaller protein repertoires. Viruses appear to play an important role in the evolution of superkingdoms. We finally identify few genomic outliers that deviate significantly from the conserved functional design. These include Nanoarchaeum equitans, proteobacterial symbionts of insects with extremely reduced genomes, Tenericutes and Guillardia theta. These organisms spend most of their domains on information functions, including translation and transcription, rather than on metabolism and harbor a domain repertoire characteristic of parasitic organisms. In contrast, the functional repertoire of the proteomes of the Planctomycetes-Verrucomicrobia-Chlamydiae superphylum was no different than the rest of bacteria, failing to support claims of them representing a separate superkingdom. In turn, Protista and Bacteria shared similar functional distribution patterns suggesting an ancestral evolutionary link between these groups.}, } @article {pmid24310356, year = {2011}, author = {Alfarouk, KO and Shayoub, ME and Muddathir, AK and Elhassan, GO and Bashir, AH}, title = {Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity).}, journal = {Cancers}, volume = {3}, number = {3}, pages = {3002-3017}, pmid = {24310356}, issn = {2072-6694}, abstract = {Carcinogenesis occurs through a series of steps from normal into benign and finally malignant phenotype. This cancer evolutionary trajectory has been accompanied by similar metabolic transformation from normal metabolism into Pasteur and/or Crabtree-Effects into Warburg-Effect and finally Cannibalism and/or Lactate-Symbiosis. Due to lactate production as an end-product of glycolysis, tumor colonies acquire new phenotypes that rely on lactate as energetic fuel. Presence of Warburg-Effect indicates that some tumor cells undergo partial (if not complete) de-endosymbiosis and so cancer cells have been become unicellular microorganism (anti-Dollo's Law) specially when they evolve to develop cannibalism as way of metabolism while oxidative types of cells that rely on lactate, as their energetic fuel, might represent extra-endosymbiosis. Thus, at the end, the cancer colony could be considered as integrated metabolic ecosystem. Proper understanding of tumor metabolism will contribute to discover potential anticancer agents besides conventional chemotherapy.}, } @article {pmid23766221, year = {2010}, author = {Rosenberg, E and Sharon, G and Atad, I and Zilber-Rosenberg, I}, title = {The evolution of animals and plants via symbiosis with microorganisms.}, journal = {Environmental microbiology reports}, volume = {2}, number = {4}, pages = {500-506}, doi = {10.1111/j.1758-2229.2010.00177.x}, pmid = {23766221}, issn = {1758-2229}, abstract = {Animals and plants evolved from prokaryotes and have remained in close association with them. We suggest that early eukaryotic cells, formed by the fusion of two or more prokaryotes, already contained prokaryotic genetic information for aggregation and the formation of multicellular structures. The hologenome theory of evolution posits that a unit of selection in evolution is the holobiont (host plus symbionts). The hologenome is defined as the genetic information of the host and its microbiota, which function in consortium. Genetic variation of the holobiont, the raw material for evolution, can arise from changes in either the host or the symbiotic microbiota genomes. Changes in the hologenome can occur by two processes that are specific to holobionts: microbial amplification and acquisition of novel strains from the environment. Recent data from culture-independent studies provides considerable support of the hologenome theory: (i) all animals and plants contain abundant and diverse microbiota, (ii) the symbiotic microbiota affects the fitness of their host and (iii) symbiotic microorganisms are transmitted from parent to offspring. Consideration of the dynamic aspects of symbioses of hosts with their diverse microbiota leads to the conclusion that holobionts can evolve not only via Darwinian but also by adaptive Lamarckian principles.}, } @article {pmid22736827, year = {2009}, author = {Craig, JP and Bekal, S and Niblack, T and Domier, L and Lambert, KN}, title = {Evidence for horizontally transferred genes involved in the biosynthesis of vitamin B(1), B(5), and B(7) in Heterodera glycines.}, journal = {Journal of nematology}, volume = {41}, number = {4}, pages = {281-290}, pmid = {22736827}, issn = {0022-300X}, abstract = {Heterodera glycines is a nematode that is highly adapted to manipulate and parasitize plant hosts. The molecular players involved in these interactions have only recently begun to be identified. Here, the sequencing of the second stage juvenile transcriptome, followed by a bioinformatic screen for novel genes, identified seven new genes involved in biosynthesis and salvage of vitamins B1, B5, and B7. With no confirmed reports in the literature, each of these biosynthesis pathways is believed to have been lost in multicellular animals. However, eukaryotic-like introns in the genomic sequences of the genes confirmed eukaryotic origin and nematode-specific splice leaders found on five of the cDNAs confirmed their nematode origin. Two of the genes were found to be flanked by known nematode sequences and quantitative polymerase chain reactions on individual nematodes showed similar and consistent amplification between the vitamin B biosynthesis genes and other known H. glycines genes. This further confirmed their presence in the nematode genome. Similarity to bacterial sequences at the amino acid level suggested a prokaryotic ancestry and phylogenetic analysis of the genes supported a likely horizontal gene transfer event, suggesting H. glycines re-appropriated the genes from the prokaryotic kingdom. This finding complements the previous discovery of a vitamin B6 biosynthesis pathway within the nematode. However, unlike the complete vitamin B6 pathway, many of these vitamin B pathways appear to be missing the initial enzymes required for full de novo biosynthesis, suggesting that initial substrates in the pathways are obtained exogenously. These partial vitamin B biosynthesis enzymes have recently been identified in other single-celled eukaryotic parasites and on rhizobia symbiosis plasmids, indicating that they may play an important role in host-parasite interactions and survival within the plant environment.}, } @article {pmid21392302, year = {2009}, author = {Renard, E and Vacelet, J and Gazave, E and Lapébie, P and Borchiellini, C and Ereskovsky, AV}, title = {Origin of the neuro-sensory system: new and expected insights from sponges.}, journal = {Integrative zoology}, volume = {4}, number = {3}, pages = {294-308}, doi = {10.1111/j.1749-4877.2009.00167.x}, pmid = {21392302}, issn = {1749-4877}, mesh = {Animals ; *Biological Evolution ; Calcium/metabolism ; Larva/anatomy & histology/physiology ; *Nervous System Physiological Phenomena ; Neurotransmitter Agents/metabolism ; Phylogeny ; Porifera/*anatomy & histology/genetics/physiology ; Sensation/*physiology ; Signal Transduction/*physiology ; }, abstract = {The capacity of all cells to respond to stimuli implies the conduction of information at least over short distances. In multicellular organisms, more complex systems of integration and coordination of activities are necessary. In most animals, the processing of information is performed by a nervous system. Among the most basal taxa, sponges are nerveless so that it is traditionally assumed that the integrated neuro-sensory system originated only once in Eumetazoa, a hypothesis not in agreement with some recent phylogenomic studies. The aim of this review is to show that recent data on sponges might provide clues for understanding the origin of this complex system. First, sponges are able to react to external stimuli, and some of them display spontaneous movement activities. These coordinated behaviors involve nervous system-like mechanisms, such as action potentials and/or neurotransmitters. Second, genomic analyses show that sponges possess genes orthologous to those involved in the patterning or functioning of the neuro-sensory system in Eumetazoa. Finally, some of these genes are expressed in specific cells (flask cells, choanocytes). Together with ultrastructural data, this gives rise to challenging hypotheses concerning cell types that might play neuro-sensory-like roles in sponges.}, } @article {pmid21669857, year = {2009}, author = {Cannon, JP}, title = {Plasticity of the immunoglobulin domain in the evolution of immunity.}, journal = {Integrative and comparative biology}, volume = {49}, number = {2}, pages = {187-196}, doi = {10.1093/icb/icp018}, pmid = {21669857}, issn = {1557-7023}, abstract = {Immune receptors are omnipresent in multicellular organisms and comprise a vast array of molecular structures that serve to detect and eliminate pathogenic threats. The immunoglobulin (Ig) domain, a central structural feature of the antigen binding receptors that mediate adaptive immunity in jawed vertebrates, appears to play a particularly widespread role in metazoan immunity. Recent reports also have implicated Ig domains in the immune responses of protostomes such as flies and snails. Our research has focused on understanding the utilization of the Ig domain in the immunity of chordates and has identified numerous multigene families of Ig domain-containing receptors that appear to serve roles distinct from the adaptive antigen-binding receptors. Three families have received particular focus: novel immune-type receptors (NITRs) of bony fish, modular domain immune-type receptors (MDIRs) of cartilaginous fish and variable region-containing chitin-binding proteins (VCBPs) of amphioxus. NITRs and MDIRs are encoded in large multigene families of highly diversified forms and exhibit a striking dichotomy of an apparently ubiquitous presence but extensive diversification of sequence both within and among the particular taxonomic groups in which they are found. Crystal structures of VCBPs and NITRs demonstrate significant similarity to those of antigen-binding receptors but at the same time exhibit key differences that imply acquisition of separate and distinct ligand-binding functions. The tremendous plasticity of the Ig domain makes it a strong focus for studies of evolutionary events that have shaped modern integrated immune systems. Current data are consistent with a model of extremely rapid emergence and divergence of immune receptors, perhaps specific to individual species, as organisms contend with environments in which pathogens are continually selected for variation of their own molecular signatures.}, } @article {pmid21669854, year = {2009}, author = {Crockford, SJ}, title = {Evolutionary roots of iodine and thyroid hormones in cell-cell signaling.}, journal = {Integrative and comparative biology}, volume = {49}, number = {2}, pages = {155-166}, doi = {10.1093/icb/icp053}, pmid = {21669854}, issn = {1557-7023}, abstract = {In vertebrates, thyroid hormones (THs, thyroxine, and triiodothyronine) are critical cell signaling molecules. THs regulate and coordinate physiology within and between cells, tissues, and whole organisms, in addition to controlling embryonic growth and development, via dose-dependent regulatory effects on essential genes. While invertebrates and plants do not have thyroid glands, many utilize THs for development, while others store iodine as TH derivatives or TH precursor molecules (iodotyrosines)-or produce similar hormones that act in analogous ways. Such common developmental roles for iodotyrosines across kingdoms suggest that a common endocrine signaling mechanism may account for coordinated evolutionary change in all multi-cellular organisms. Here, I expand my earlier hypothesis for the role of THs in vertebrate evolution by proposing a critical evolutionary role for iodine, the essential ingredient in all iodotyrosines and THs. Iodine is known to be crucial for life in many unicellular organisms (including evolutionarily ancient cyanobacteria), in part, because it acts as a powerful antioxidant. I propose that during the last 3-4 billion years, the ease with which various iodine species become volatile, react with simple organic compounds, and catalyze biochemical reactions explains why iodine became an essential constituent of life and the Earth's atmosphere-and a potential marker for the origins of life. From an initial role as membrane antioxidant and biochemical catalyst, spontaneous coupling of iodine with tyrosine appears to have created a versatile, highly reactive and mobile molecule, which over time became integrated into the machinery of energy production, gene function, and DNA replication in mitochondria. Iodotyrosines later coupled together to form THs, the ubiquitous cell-signaling molecules used by all vertebrates. Thus, due to their evolutionary history, THs, and their derivative and precursors molecules not only became essential for communicating within and between cells, tissues and organs, and for coordinating development and whole-body physiology in vertebrates, but they can also be shared between organisms from different kingdoms.}, } @article {pmid21356734, year = {2008}, author = {Degnan, BM and Adamska, M and Craigie, A and Degnan, SM and Fahey, B and Gauthier, M and Hooper, JN and Larroux, C and Leys, SP and Lovas, E and Richards, GS}, title = {The Demosponge Amphimedon queenslandica: Reconstructing the Ancestral Metazoan Genome and Deciphering the Origin of Animal Multicellularity.}, journal = {CSH protocols}, volume = {2008}, number = {}, pages = {pdb.emo108}, doi = {10.1101/pdb.emo108}, pmid = {21356734}, abstract = {INTRODUCTIONSponges are one of the earliest branching metazoans. In addition to undergoing complex development and differentiation, they can regenerate via stem cells and can discern self from nonself ("allorecognition"), making them a useful comparative model for a range of metazoan-specific processes. Molecular analyses of these processes have the potential to reveal ancient homologies shared among all living animals and critical genomic innovations that underpin metazoan multicellularity. Amphimedon queenslandica (Porifera, Demospongiae, Haplosclerida, Niphatidae) is the first poriferan representative to have its genome sequenced, assembled, and annotated. Amphimedon exemplifies many sessile and sedentary marine invertebrates (e.g., corals, ascidians, bryozoans): They disperse during a planktonic larval phase, settle in the vicinity of conspecifics, ward off potential competitors (including incompatible genotypes), and ensure that brooded eggs are fertilized by conspecific sperm. Using genomic and expressed sequence tag (EST) resources from Amphimedon, functional genomic approaches can be applied to a wide range of ecological and population genetic processes, including fertilization, dispersal, and colonization dynamics, host-symbiont interactions, and secondary metabolite production. Unlike most other sponges, Amphimedon produce hundreds of asynchronously developing embryos and larvae year-round in distinct, easily accessible brood chambers. Embryogenesis gives rise to larvae with at least a dozen cell types that are segregated into three layers and patterned along the body axis. In this article, we describe some of the methods currently available for studying A. queenslandica, focusing on the analysis of embryos, larvae, and post-larvae.}, } @article {pmid21669754, year = {2007}, author = {Lavrov, DV}, title = {Key transitions in animal evolution: a mitochondrial DNA perspective.}, journal = {Integrative and comparative biology}, volume = {47}, number = {5}, pages = {734-743}, doi = {10.1093/icb/icm045}, pmid = {21669754}, issn = {1540-7063}, abstract = {Animal mitochondrial DNA (mtDNA) is usually depicted as a small and very economically organized molecule with almost invariable gene content, stable gene order, a high rate of sequence evolution, and several unorthodox genetic features. Sampling across different animal phyla reveals that such a description applies primarily to mtDNA of bilaterian animals (such as arthropods or chordates). By contrast, mitochondrial genomes of nonbilaterian animals (phyla Cnidaria, Placozoa, and Porifera) display more variation in size and gene content and, in most cases, lack the genetic novelties associated with bilaterian mtDNA. Outside the Metazoa, mtDNA of the choanoflagellate Monosiga brevicollis, the closest unicellular out-group, is a much larger molecule that contains a large proportion of noncoding DNA, 1.5 times more genes, as well as several introns. Thus, changes in animal mtDNA organization appear to correlate with two main transitions in animal evolution: the origin of multicellularity and the origin of the Bilateria. Studies of mtDNA in nonbilaterian animals provide valuable insights into these transitions in the organization of mtDNA and also supply data for phylogenetic analyses of the relationships of early animals. Here I review recent progress in the understanding of nonbilaterian mtDNA and discuss the advantages and limitations of mitochondrial data sets for inferences about the phylogeny and evolution of animals.}, } @article {pmid21669753, year = {2007}, author = {Blackstone, NW}, title = {A food's-eye view of the transition from basal metazoans to bilaterians.}, journal = {Integrative and comparative biology}, volume = {47}, number = {5}, pages = {724-733}, doi = {10.1093/icb/icm056}, pmid = {21669753}, issn = {1540-7063}, abstract = {Living things invariably consist of some kind of compartmentalized redox chemistry. Signaling pathways mediated by oxidation and reduction thus derive from the nature of life itself. The role of such redox or metabolic signaling broadened with major transitions in the history of life. Prokaryotes often use redox signals to deploy one or more variant electron carriers and associated enzymes to better utilize environmental energy sources. Eukaryotes transcend the strong surface-to-volume constraints inherent in prokaryotic cells by moving chemiosmotic membranes internally. As a consequence, eukaryotic redox signaling is frequently between these organelle membranes and the nucleus, thus potentially involving levels-of-selection synergies and antagonisms. Gradients of oxygen and substrate in simple multicellular organisms similarly associated metabolic signaling with levels of selection, now at the level of the cell and the organism. By allowing sequestration of large amounts of food, the evolution of the animal mouth was a pivotal event in metabolic signaling, leading to "multicellular" redox regulation. Because concentrated food resources may be patchy in time and space, long-lived sedentary animals with mouths employ such metabolic signaling and phenotypic plasticity in ways that adapt them to the changing availability of food. Alternatively, if the mouth is coupled to a battery of sensory equipment, the organism can actively seek out and sequester patches of food. In these early bilaterians, competition for food resources may have favored rapid development with little subsequent plasticity and metabolic signaling. With rapid dispersal and colonization, such "assembly-line" animals could effectively compete for patchy resources. Limiting metabolic signaling, however, resulted in a cascade of seemingly unrelated changes. These changes derive from the effectiveness of metabolic signaling in policing variation at the cellular level. If the signals an organism uses to control cellular replication are the same as the signals a cell uses to control its own metabolism, then cells that ignore these signals and carry out selfish replication will pay a fitness cost in terms of inefficient metabolism. Bilaterians with limited metabolic signaling thus require other mechanisms to police cell-level variation. Bilaterian features such as restricted somatic cell potency, a sequestered germ line, and determinate growth should be viewed in this context. Bilaterian senescence evolved as a by-product of restricted potency of somatic cells, itself a mechanism of cell policing required by limited metabolic signaling.}, } @article {pmid21669752, year = {2007}, author = {Jacobs, DK and Nakanishi, N and Yuan, D and Camara, A and Nichols, SA and Hartenstein, V}, title = {Evolution of sensory structures in basal metazoa.}, journal = {Integrative and comparative biology}, volume = {47}, number = {5}, pages = {712-723}, doi = {10.1093/icb/icm094}, pmid = {21669752}, issn = {1540-7063}, abstract = {Cnidaria have traditionally been viewed as the most basal animals with complex, organ-like multicellular structures dedicated to sensory perception. However, sponges also have a surprising range of the genes required for sensory and neural functions in Bilateria. Here, we: (1) discuss "sense organ" regulatory genes, including; sine oculis, Brain 3, and eyes absent, that are expressed in cnidarian sense organs; (2) assess the sensory features of the planula, polyp, and medusa life-history stages of Cnidaria; and (3) discuss physiological and molecular data that suggest sensory and "neural" processes in sponges. We then develop arguments explaining the shared aspects of developmental regulation across sense organs and between sense organs and other structures. We focus on explanations involving divergent evolution from a common ancestral condition. In Bilateria, distinct sense-organ types share components of developmental-gene regulation. These regulators are also present in basal metazoans, suggesting evolution of multiple bilaterian organs from fewer antecedent sensory structures in a metazoan ancestor. More broadly, we hypothesize that developmental genetic similarities between sense organs and appendages may reflect descent from closely associated structures, or a composite organ, in the common ancestor of Cnidaria and Bilateria, and we argue that such similarities between bilaterian sense organs and kidneys may derive from a multifunctional aggregations of choanocyte-like cells in a metazoan ancestor. We hope these speculative arguments presented here will stimulate further discussion of these and related questions.}, } @article {pmid21669750, year = {2007}, author = {Boero, F and Schierwater, B and Piraino, S}, title = {Cnidarian milestones in metazoan evolution.}, journal = {Integrative and comparative biology}, volume = {47}, number = {5}, pages = {693-700}, doi = {10.1093/icb/icm041}, pmid = {21669750}, issn = {1540-7063}, abstract = {Cnidarians display most of the characters considered as milestones of metazoan evolution. Whereas a tissue-level organization was probably already present in the multicellular common ancestor of all animals, the Urmetazoa, the emergence of important animal features such as bilateral symmetry, triploblasty, a polarized nervous system, sense organs (eyes, statocysts), and a (chitinous or calcium-based) continuous skeleton can be traced back before the divergence between cnidarians and bilaterians. Modularity and metamery might be also regarded as two faces of the same medal, likely involving conserved molecular mechanisms ruling animal body architectures through regional specification of iterated units. Available evidence indicates that the common ancestor of cnidarians and bilaterians, the UrEumetazoa, was a surprisingly complex animal with nerve cell differentiation. We suggest that paedomorphic events in descendants of this ancestor led to the array of diversity seen in the main extant animal phyla. The use of molecular analyses and identifying the genetic determinants of anatomical organizations can provide an integrative test of hypotheses of homologies and independent evidence of the evolutionary relationships among extant taxa.}, } @article {pmid21672781, year = {2006}, author = {Hodin, J}, title = {Expanding networks: Signaling components in and a hypothesis for the evolution of metamorphosis.}, journal = {Integrative and comparative biology}, volume = {46}, number = {6}, pages = {719-742}, doi = {10.1093/icb/icl038}, pmid = {21672781}, issn = {1540-7063}, abstract = {Metamorphosis is a substantial morphological transition between 2 multicellular phases in an organism's life cycle, often marking the passage from a prereproductive to a reproductive life stage. It generally involves major physiological changes and a shift in habitat and feeding mode, and can be subdivided into an extended phase of substantial morphological change and/or remodeling, and a shorter-term phase (for example, marine invertebrate "settlement," insect "adult eclosion," mushroom fruiting body emergence) where the actual habitat shift occurs. Disparate metamorphic taxa differ substantially with respect to when the habitat shift occurs relative to the timing of the major events of morphogenetic change. I will present comparative evidence across a broad taxonomic scope suggesting that longer-term processes (morphogenetic changes) are generally hormonally regulated, whereas nitric oxide (NO) repressive signaling often controls the habitat shift itself. Furthermore, new evidence from echinoids (sea urchins, sand dollars) indicates a direct connection between hormonal and NO signaling during metamorphosis. I incorporate 2 hypotheses for the evolution of metamorphosis-one involving heterochrony, the other involving phenotypic integration and evolutionarily stable configurations (ESCs)-into a network model for metamorphosis in echinoderms (sea urchins, starfish, and their kin). Early indications are that this core regulatory network can be acted upon by natural selection to suit the diverse ecological needs of disparate metamorphic organisms, resulting in evolutionary expansions and contractions in the core network. I briefly speculate on the ways that exposure to xenobiotic pollutants and other compounds might influence successful settlement of juveniles in the wild. Indeed, environmentally regulated life history transitions-such as settlement, metamorphosis, and reproductive maturation-may be developmental periods that are especially sensitive to such pollutants.}, } @article {pmid21642096, year = {2006}, author = {Sperry, JS and Hacke, UG and Pittermann, J}, title = {Size and function in conifer tracheids and angiosperm vessels.}, journal = {American journal of botany}, volume = {93}, number = {10}, pages = {1490-1500}, doi = {10.3732/ajb.93.10.1490}, pmid = {21642096}, issn = {0002-9122}, abstract = {The wide size range of conifer tracheids and angiosperm vessels has important consequences for function. In both conduit types, bigger is better for conducting efficiency. The gain in efficiency with size is maximized by the control of conduit shape, which balances end-wall and lumen resistances. Although vessels are an order of magnitude longer than tracheids of the same diameter, they are not necessarily more efficient because they lack the low end-wall resistance of tracheids with torus-margo pits. Instead, vessels gain conducting efficiency over tracheids by achieving wider maximum diameters. End-walls contributed 56-64% to total xylem resistance in both conduit types, indicating that length limits conducting efficiency. Tracheid dimensions may be more limited by unicellularity and the need to supply strength to homoxylous wood than by the need to protect against cavitation. In contrast, the greater size of the multicellular vessel is facilitated by fibers that strengthen heteroxylous wood. Vessel dimensions may be most limited by the need to restrict intervessel pitting and cavitation by air-seeding. Stressful habitats that promote narrow vessels should favor coexistence of conifers and angiosperms. The evolution of vessels in angiosperm wood may have required early angiosperms to survive a phase of mechanic and hydraulic instability.}, } @article {pmid21783649, year = {2006}, author = {Silliman, CC and Wang, M}, title = {The merits of in vitro versus in vivo modeling in investigation of the immune system.}, journal = {Environmental toxicology and pharmacology}, volume = {21}, number = {2}, pages = {123-134}, doi = {10.1016/j.etap.2005.07.002}, pmid = {21783649}, issn = {1382-6689}, abstract = {Immunity is vital for determining self and for the recognition and swift eradication of foreign antigens without harming the host. Innate immunity developed in metazoan, multi-cellular organisms under overwhelming selection pressure of invasive microbes and, although imperfect, has performed admirably to enable the evolution of higher eukaryotes. Adaptive immunity developed within an existing innate immune system to more effectively eradicate foreign antigens, whether from pathogens, malignant cells, or microbial toxins, such that repeated stimulations with foreign antigens are more efficiently excluded. Investigation of the immune system requires both in vivo and in vitro experimentation, not only because of the inherent complexity of immunity and the required pertinence of using higher mammals to not falsely disrupt the immune system, but also to use isolates of the specific cellular and humoral components to determine function, signal transduction, and a possible role of these constituents without the complexity and redundancy of immunity in intact animals. The hypotheses of well-designed in vitro experiments must also be tested in intact in vivo models to determine relevance and to discard artifactual findings secondary to the in vitro environment. The following review outlines the basic constituents and functions of both adaptive and innate immunity to demonstrate the importance of both in vivo and in vitro investigation of immunity in our attempt to define host defense and to decrease morbidity and mortality in humans.}, } @article {pmid22485989, year = {2006}, author = {Davis, I and Parton, RM}, title = {Time-lapse cinematography in living Drosophila tissues: preparation of material.}, journal = {CSH protocols}, volume = {2006}, number = {6}, pages = {}, doi = {10.1101/pdb.prot4602}, pmid = {22485989}, abstract = {The fruit fly, Drosophila melanogaster, has been an extraordinarily successful model organism for studying the genetic basis of development and evolution. It is arguably the best-understood complex multicellular model system, owing its success to many factors. Recent developments in imaging techniques, in particular sophisticated fluorescence microscopy methods and equipment, now allow cellular events to be studied at high resolution in living material. This ability has enabled the study of features that tend to be lost or damaged by fixation, such as transient or dynamic events. Although many of the techniques of live cell imaging in Drosophila are shared with the greater community of cell biologists working on other model systems, studying living fly tissues presents unique difficulties in keeping the cells alive, introducing fluorescent probes, and imaging through thick hazy cytoplasm. This protocol outlines the preparation of major tissue types amenable to study by time-lapse cinematography and different methods for keeping them alive.}, } @article {pmid21676759, year = {2005}, author = {Baker, ME}, title = {Xenobiotics and the evolution of multicellular animals: emergence and diversification of ligand-activated transcription factors.}, journal = {Integrative and comparative biology}, volume = {45}, number = {1}, pages = {172-178}, doi = {10.1093/icb/45.1.172}, pmid = {21676759}, issn = {1540-7063}, abstract = {Multicellular animals, which evolved about 700 to 1,000 myr ago, contain many of the genes found in yeast. Important for the evolution of multicellular animals were new pathways for intercellular signaling that regulated more complex physiological responses. Here we focus on the contribution to this process of lipophilic molecules that interact with nuclear receptors and the aryl hydrocarbon receptor, as well as enzymes that regulate the concentrations of these molecules. Both nuclear receptors and the aryl hydrocarbon receptor are found in invertebrates and vertebrates. We propose that environmental chemicals (xenobiotics) have been an important influence on the evolution of multicellular animals through a process involving the co-evolution of ligand-activated transcription factors and enzymes that detoxify xenobiotics. Indeed, this conversion of "xenobiotic swords" into "adaptive plowshares" contributed to the diverse physiology found in multicelluar animals. An important implication of this analysis is that enzymes as well as hormone receptors are vulnerable targets for endocrine disruptors. That is, some toxic chemicals act by inhibiting the enzymes that catalyze the formation or degradation of lipophilic signals, such as steroids, thus, disrupting hormone action.}, } @article {pmid21653378, year = {2004}, author = {Xiao, S and Knoll, AH and Yuan, X and Pueschel, CM}, title = {Phosphatized multicellular algae in the Neoproterozoic Doushantuo Formation, China, and the early evolution of florideophyte red algae.}, journal = {American journal of botany}, volume = {91}, number = {2}, pages = {214-227}, doi = {10.3732/ajb.91.2.214}, pmid = {21653378}, issn = {0002-9122}, abstract = {Phosphatic sediments of the Late Neoproterozoic (ca. 600 million years old [Myr]) Doushantuo Formation at Weng'an, South China, contain fossils of multicellular algae preserved in anatomical detail. As revealed by light microscopy and scanning electron microscopy, these fossils include both simple pseudoparenchymatous thalli with apical growth but no cortex-medulla differentiation and more complex thalli characterized by cortex-medulla differentiation and structures interpretable as carposporophytes, suggesting a multiphasic life cycle. Simple pseudoparenchymatous thalli, represented by Wengania, Gremiphyca, and Thallophycoides, are interpreted as stem group florideophytes. In contrast, complex pseudoparenchymatous thalli, such as Thallophyca and Paramecia, compare more closely to fossil and living corallinaleans than to other florideophyte orders, although they also differ in some important aspects (e.g., lack of biocalcification). These more complex thalli are interpreted as early stem group corallinaleans that diverged before Paleozoic stem groups such as Arenigiphyllum, Petrophyton, Graticula, and Archaeolithophyllum. This phylogenetic interpretation implies that (1) the phylogenetic divergence between the Florideophyceae and its sister group, the Bangiales, must have taken place before Doushantuo time-an inference supported by the occurrence of bangialean fossils in Mesoproterozoic rocks; (2) the initial diversification of the florideophytes occurred no later than the Doushantuo time; and (3) the corallinalean clade had a "soft" (uncalcified) evolutionary history in the Neoproterozoic before evolving biocalcification in the Paleozoic and undergoing crown group diversification in the Mesozoic.}, } @article {pmid21680429, year = {2003}, author = {Kirk, DL}, title = {Seeking the ultimate and proximate causes of volvox multicellularity and cellular differentiation.}, journal = {Integrative and comparative biology}, volume = {43}, number = {2}, pages = {247-253}, doi = {10.1093/icb/43.2.247}, pmid = {21680429}, issn = {1540-7063}, abstract = {Volvox and its relatives provide an exceptional model for integrative studies of the evolution of multicellularity and cellular differentiation. The volvocine algae range in complexity from unicellular Chlamydomonas through several colonial genera with a single cell type, to multicellular Volvox with its germ-soma division of labor. Within the monophyletic family Volvocaceae, several species of Volvox have evolved independently in different lineages, the ultimate cause presumably being the advantage that large size and cellular differentiation provide in competing for limiting resources such as phosphorous. The proximate causes of this type of evolutionary transition are being studied in V. carteri. All volvocine algae except Volvox exhibit biphasic development: cells grow during a motile, biflagellate phase, then they lose motility and divide repeatedly during the reproductive phase. In V. carteri three kinds of genes transform this ancestral biphasic program into a dichotomous one that generates non-motile reproductive cells and biflagellate somatic cells with no reproductive potential: first the gls genes act in early embryos to cause asymmetric division and production of large-small sister-cell pairs; then lag genes act in the large cells to repress the biflagellate half of the ancestral program, while regA acts in the small cells to repress the reproductive half of the program. Molecular-genetic analysis of these genes is progressing, as will be illustrated with regA, which encodes a transcription factor that acts in somatic cells to repress nuclear genes encoding chloroplast proteins. Repression of chloroplast biogenesis prevents these obligately photoautotrophic cells from growing, and since they cannot grow, they cannot reproduce.}, } @article {pmid21680411, year = {2003}, author = {McShea, DW and Changizi, MA}, title = {Three puzzles in hierarchical evolution.}, journal = {Integrative and comparative biology}, volume = {43}, number = {1}, pages = {74-81}, doi = {10.1093/icb/43.1.74}, pmid = {21680411}, issn = {1540-7063}, abstract = {The maximum degree of hierarchical structure of organisms has risen over the history of life, notably in three transitions: the origin of the eukaryotic cell from symbiotic associations of prokaryotes; the emergence of the first multicellular individuals from clones of eukaryotic cells; and the origin of the first individuated colonies from associations of multicellular organisms. The trend is obvious in the fossil record, but documenting it using a high-resolution hierarchy scale reveals three puzzles: 1) the rate of origin of new levels accelerates, at least until the early Phanerozoic; 2) after that, the trend may slow or even stop; and 3) levels may sometimes arise out of order. The three puzzles and their implications are discussed; a possible explanation is offered for the first.}, } @article {pmid21680410, year = {2003}, author = {Michod, RE and Nedelcu, AM}, title = {On the reorganization of fitness during evolutionary transitions in individuality.}, journal = {Integrative and comparative biology}, volume = {43}, number = {1}, pages = {64-73}, doi = {10.1093/icb/43.1.64}, pmid = {21680410}, issn = {1540-7063}, abstract = {The basic problem in an evolutionary transition is to understand how a group of individuals becomes a new kind of individual, possessing the property of heritable variation in fitness at the new level of organization. During an evolutionary transition, for example, from single cells to multicellular organisms, the new higher-level evolutionary unit (multicellular organism) gains its emergent properties by virtue of the interactions among lower-level units (cells). We see the formation of cooperative interactions among lower-level units as a necessary step in evolutionary transitions; only cooperation transfers fitness from lower levels (costs to group members) to higher levels (benefits to the group). As cooperation creates new levels of fitness, it creates the opportunity for conflict between levels as deleterious mutants arise and spread within the group. Fundamental to the emergence of a new higher-level unit is the mediation of conflict among lower-level units in favor of the higher-level unit. The acquisition of heritable variation in fitness at the new level, via conflict mediation, requires the reorganization of the basic components of fitness (survival and reproduction) and life-properties (such as immortality and totipotency) as well as the co-option of lower-level processes for new functions at the higher level. The way in which the conflicts associated with the transition in individuality have been mediated, and fitness and general life-traits have been re-organized, can influence the potential for further evolution (i.e., evolvability) of the newly emerged evolutionary individual. We use the volvocalean green algal group as a model-system to understand evolutionary transitions in individuality and to apply and test the theoretical principles presented above. Lastly, we discuss how the different notions of individuality stem from the basic properties of fitness in a multilevel selection context.}, } @article {pmid21544390, year = {1996}, author = {Pfragner, R and Wirnsberger, G and Niederle, B and Behmel, A and Rinner, I and Mandl, A and Wawrina, F and Luo, J and Adamiker, D and Hoger, H and Ingolic, E and Schauenstein, K}, title = {Establishment of a continuous cell line from a human carcinoid of the small intestine (KRJ-I).}, journal = {International journal of oncology}, volume = {8}, number = {3}, pages = {513-520}, doi = {10.3892/ijo.8.3.513}, pmid = {21544390}, issn = {1019-6439}, abstract = {A new continuous cell line from a human malignant carcinoid of the small intestine (KRJ-I) was established. The cells showed morphological and immunocytochemical features of the tumor of origin and expressed estrogen receptors. The cells are growing as a suspension, forming multicellular aggregates and spheroids. Electron microscopy confirmed the presence of neuroendocrine granules. Dose-dependent growth inhibition was observed after incubation with 5-azacytidine. Cytogenetic analyses of the tumor of origin, the cell line KRJ-I and a liver metastasis KRJ-II revealed clonal tetraploidy and clonal loss of the Y-chromosome and chromosome 19.}, } @article {pmid21573384, year = {1993}, author = {Chigira, M}, title = {Selfish cells in altruistic cell society - a theoretical oncology.}, journal = {International journal of oncology}, volume = {3}, number = {3}, pages = {441-455}, doi = {10.3892/ijo.3.3.441}, pmid = {21573384}, issn = {1019-6439}, abstract = {In multicellular organisms, internal evolution of individual cells is strictly forbidden and 'evolutional' DNA replication should be performed only by the sexual reproduction system. Wholistic negative control system called 'homeostasis' serves all service to germ line cells. All somatic cells are altruistic to the germ line cells. However, in malignant tumors, it seems that individual cells replicate and behave 'selfishly' and evolve against the internal microenvironment. Tumor cells only express the occult selfishness which is programmed in normal cells a priori. This phenomenon is based on the failure of identical DNA replication, and results in 'autonomy' and 'anomie' of cellular society as shown in tumor cells. Genetic programs of normal cells connote this cellular autonomy and anomie introduced by the deletion of regulators on structure genes. It is rather paradoxical that the somatic cells get their freedom from wholistic negative regulation programmed internally. However, this is not a true paradox, since multicellular organisms have clearly been evolved from 'monads' in which cells proliferate without wholistic regulation. Somatic cells revolt against germ cell DNA, called 'selfish replicator' by Dawkins. It is an inevitable destiny that the 'selfishness' coded in genome should be revenged by itself. Selfish replicator in germ cell line should be revolted by its selfishness in the expansion of somatic cells, since they have an orthogenesis to get more selfishness in order to increase their genome. Tumor heterogeneity and progression can be fully explained by this self-contradictory process which produces heterogeneous gene copies different from the original clone in the tumor, although 'selfish' gene replication is the final target of being. Furthermore, we have to discard the concept of clonality of tumor cells since genetic instability is a fundamental feature of tumors. Finally, tumor cells and proto-oncogenes can be considered as the ultimate parasite to germ line cells.}, } @article {pmid24197340, year = {1993}, author = {Polgár, Z and Preiszner, J and Dudits, D and Fehér, A}, title = {Vigorous growth of fusion products allows highly efficient selection of interspecific potato somatic hybrids: molecular proofs.}, journal = {Plant cell reports}, volume = {12}, number = {7-8}, pages = {399-402}, pmid = {24197340}, issn = {0721-7714}, abstract = {An early identification of fusion products was based on the presumed vigorous growth of hybrid calluses after fusion between Solanum brevidens and S. tuberosum leaf protoplasts. The S. brevidens protoplasts were unable to form multicellular colonies under the applied culture conditions. Three size groups of calluses were separated and analyzed at two different early phases of culture period. "Squash blot" hybridization with a S. brevidens specific repetitive DNA probe showed that the group of the largest calluses consisted of putative somatic hybrids with a frequency of 80-100% in three independent experiments. Furthermore, approximately 80-95% of the middle sized calluses and 33-90% of the smallest ones were shown to be hybrid. The unexpectedly high percentage of fusion products, even in the case of the smallest calluses, may result from the suppression of the development of parental potato colonies in cultures with mixed cell population. Till this time 120 independent colonies selected as putative hybrids have been regenerated into plants. All of them exhibited hybrid phenotype, and their hybrid origin was proved by cytological and restriction fragment length polymorphism analyses.}, } @article {pmid21573595, year = {1993}, author = {Chigira, M}, title = {Origin of autonomy and anomie of tumors in cell society (hypothesis).}, journal = {International journal of oncology}, volume = {2}, number = {4}, pages = {583-586}, doi = {10.3892/ijo.2.4.583}, pmid = {21573595}, issn = {1019-6439}, abstract = {In multicellular organisms, internal evolution of individual cells is strictly forbidden and 'evolutional' DNA replication should be performed only by the sexual reproduction system in these organisms, although in malignant tumors, it seems that individual cells replicate 'selfishly' and evolve against the internal micro-environment. This phenomenon is based on the failure of identical DNA replication, and results in 'anomie' of cellular society. Genetic programs of normal cells connote this cellular anomie, since they are introduced by the deletion of regulators on structure genes and cells have clearly been evolved from 'monads' in which cells proliferate without regulation. Tumor heterogeneity and progression can be fully explained by this self-contradictory process which produces heterogeneous gene copies different from the original clone in the tumor, although 'selfish' gene replication is the final target of being.}, } @article {pmid24186661, year = {1992}, author = {Dibb-Fuller, JE and Morris, DA}, title = {Studies on the evolution of auxin carriers and phytotropin receptors: Transmembrane auxin transport in unicellular and multicellular Chlorophyta.}, journal = {Planta}, volume = {186}, number = {2}, pages = {219-226}, pmid = {24186661}, issn = {0032-0935}, abstract = {The characteristics of transmembrane transport of (14)C-labelled indol-3yl-acetic acid ([1-(14)C]IAA) were compared in Chlorella vulgaris Beij., a simple unicellular green alga, and in Chara vulgaris L., a branched, multicellular green alga exhibiting axial polarity and a high degree of cell and organ specialization. In Chara thallus cells, three distinguishable trans-plasmamembrane fluxes contributed to the net uptake of [1-(14)C]-IAA from an external solution, viz.: a non-mediated, pH-sensitive influx of undissociated IAA (IAAH); a saturable influx of IAA; and a saturable efflux of IAA. Both saturable fluxes were competitively inhibited by unlabelled IAA. Association of [(3)H]IAA with microsomal preparations from Chara thallus tissue was competitively inhibited by unlabelled IAA. Results indicated that up-take carriers occurred in the membranes at a much higher density than efflux carriers. The efflux component of IAA net uptake by Chara was not affected by several phytotropins (N-1-naphthylphthalmic acid, NPA; 2-(1-pyrenoyl)benzoic acid; and 5-(2-carboxyphenyl)-3-phenylpyrazole), which are potent non-competitive inhibitors of specific auxin-efflux carriers in more advanced plant groups, and no evidence was found for a specific association of [(3)H]NPA with Chara microsomal preparations. It was concluded that Chara lacked phytotropin receptors. Net uptake of [1-(14)C]IAA also was unaffected by 2,3,5-triiodobenzoic acid except at concentrations (≥ 10(-1) mol · m(-3)) high enough to depress cytoplasmic pH (determined by uptake of 5,5-dimethyloxazolidine-2,4-dione). Chlorella cells accumulated [1-(14)C]IAA from an external solution by pH-sensitive diffusion of IAA across the plasma membrane and anion (IAA(-)) trapping, but no evidence was found in Chlorella for the occurrence of IAA carriers. These results indicate that carrier systems capable of mediating the transmembrane transport of auxins appeared at a very early stage in the evolution of green plants, possibly in association with the origin of a differentiated, multicellular plant body. Phytotropin receptors evolved independently of the carriers.}, } @article {pmid23194754, year = {1991}, author = {Schlegel, M}, title = {Protist evolution and phylogeny as discerned from small subunit ribosomal RNA sequence comparisons.}, journal = {European journal of protistology}, volume = {27}, number = {3}, pages = {207-219}, doi = {10.1016/S0932-4739(11)80059-3}, pmid = {23194754}, issn = {0932-4739}, abstract = {Ribosomal RNA sequence comparisons reveal an evolutionary diversity among unicellular eukaryotes far exceeding that observed within the multicellular or prokaryote kingdoms. The analysis of small subunit ribosomal RNAs provides new insights into the evolution and phylogenetic relationships of major lineages. The parasitic diplomonad flagellate Giardia lamblia diverges first on the eukaryotic tree, followed by another parasite, the microsporidian Vairimorpha necatrix. Further, a close relationship between apicomplexa, dinoflagellates and ciliates is evident from sequence comparisons. The eumycetes or true fungi are separated from the oomycetes. However, phylogenetic relationships between the major protist lineages, as well as their relationships to both prokaryotes and multicellular organisms cannot be discerned by analysis of small subunit rRNA sequences alone. Additional molecular information, for example from large subunit rRNA, or polymerase genes are requested to gain confidence in branching patterns displayed in the small subunit rRNA trees. Advantages and disadvantages of commonly used treeing methods are briefly discussed as well as the current views on the phylogenetic relationships between eukaryotes, archaebacteria and eubacteria.}, } @article {pmid24202013, year = {1990}, author = {Battey, JF and Ohlrogge, JB}, title = {Evolutionary and tissue-specific control of expression of multiple acyl-carrier protein isoforms in plants and bacteria.}, journal = {Planta}, volume = {180}, number = {3}, pages = {352-360}, doi = {10.1007/BF00198786}, pmid = {24202013}, issn = {0032-0935}, abstract = {We have examined the occurrence of multiple acyl-carrier protein (ACP), isoforms in evolutionarily diverse species of higher and lower plants. Isoforms were resolved by native polyacrylamide gel electrophoresis (PAGE), and were detected by Western blotting or fluorography of [(3)H]-palmitate-labelled ACPs. Multiple isoforms of ACP were found in leaf tissue of the monocotyledons Avena sativa and Hordeum vulgare and dicotyledons Arabidopsis thaliana, Cuphea wrightii, and Brassica napus. Lower vascular plants including the lycopod Selaginella krausseriana, the gymnosperms Ephedra sp. and Dioon edule, the ferns Davallia feejensis and Marsilea sp. and the most primitive known extant vascular plant, Psilotum nudum, were all found to have multiple ACP isoforms, as were the nonvascular liverworts, Lunularia sp. and Marchantia sp. and the moss, Polytrichum sp. Therefore, the development of ACP isoforms appears to have occurred early in plant evolution. However, we could detect only a single electrophoretic form of ACP in the unicellular algae Chlamydomonas reinhardtii and Dunaliella tertiolecta and the photosynthetic cyanobacteria Synechocystis strain 6803 and Agmnellum quadruplicatum. Thus, multiple forms of ACP do not occur in all photosynthetic organisms but may be associated with multicellular plants. We have also examined tissue specificity and light control over the expression of ACP isoforms. The relative abundance of multiple forms of ACP in leaf of Spinacia and Avena was altered very little by light. Rather, the different patterns of ACP isoforms were primarily dependent on the tissue type.}, } @article {pmid24240443, year = {1989}, author = {Parrott, WA and Hoffman, LM and Hildebrand, DF and Williams, EG and Collins, GB}, title = {Recovery of primary transformants of soybean.}, journal = {Plant cell reports}, volume = {7}, number = {8}, pages = {615-617}, pmid = {24240443}, issn = {0721-7714}, abstract = {Three transformants of soybean, Glycine max (L.) Merr., have been recovered among a total of 18 plants regenerated by somatic embryogenesis from immature cotyledon tissues after cocultivation with Agrobacterium strains carrying a 15 kD zein gene (pH5PZ3D). DNA from upper leaves hybridized to a synthetic RNA probe specific for the zein sequence at a level equivalent to at least one copy per haploid genome. Hybridization to a vir G/C probe, however, was negligible, indicating that sequestration of whole bacteria or even persistence of plasmids within the tissues could not account for the zein hybridization signals. Progeny of all plants were uniformly untransformed. Since most somatic embryos have a multicellular origin in the regeneration system used, it is believed that the primary transformants were chimeric. The results indicate that somatic embryogenesis may be adaptable to Agrobacterium-mediated transformation in soybean, but that greater numbers of mitotic cycles under selection before embryo initiation will be required if somatic embryogenesis is to be used efficiently for production of plants with transformed germ-line cells.}, } @article {pmid24424476, year = {1974}, author = {Sree Rangasamy, SR and Sree Ramulu, K}, title = {Effect of X-irradiation on the size of the mutated sector in diploid and tetraploid rice.}, journal = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik}, volume = {44}, number = {6}, pages = {266-269}, pmid = {24424476}, issn = {0040-5752}, abstract = {An investigation was carried out of the effect of X-irradiation on the size of the mutated sector in three diploids (A.S.D.8, T.N. 1 and G.E.B. 24) and the autotetraploid of G.E.B 24 of Oryza sativa L., by analyzing the M2 segregation ratios of chlorophyll mutants. A total of 612 segregating M1 panicle progenies in the diploids and 284 panicle progenies in the tetraploid was studied in the M2 generation for the ratio of normal to chlorophyll mutant seedlings. Of the 573 segregating M1 panicles analysed by chi square test in the diploids, 206 showed good fit with a 3∶1 ratio, while the rest of the progenies (367) deviated significantly in both directions from the expected 3∶1 segregation. This was interpreted as the result of M1 panicles developing from both single cell and multicellular initials following X-irradiation, the former segregating for 3∶1, the latter significantly deviating from 3∶1. An assessment of fertility (as judged from the number of M2 seedlings per mutated M1 panicle), related to the distribution of chi square deviations from the 3∶1 ratio in the diploids, indicated that the M1 panicle progenies deriving from single cell initials had low fertility but those originating from multicellular initials ranged from low to high fertility. A comparison of the distribution pattern of the M2 segregation ratios of chlorophyll mutant phenotypes in the diploid and autotetraploid G.E.B. 24 indicated that, in the tetraploid, a larger sector and only one, or fewer cell initials than in the diploid species, are involved.}, } @article {pmid21347361, year = {2011}, author = {Piganeau, G and Eyre-Walker, A and Jancek, S and Grimsley, N and Moreau, H}, title = {How and why DNA barcodes underestimate the diversity of microbial eukaryotes.}, journal = {PloS one}, volume = {6}, number = {2}, pages = {e16342}, pmid = {21347361}, issn = {1932-6203}, mesh = {Animals ; *Biodiversity ; DNA Barcoding, Taxonomic/*methods ; DNA, Ribosomal/genetics ; Eukaryota/classification/*genetics ; Evolution, Molecular ; Genome/genetics ; Humans ; Mice ; Plankton/classification/*genetics ; Proteome/genetics ; Rats ; }, abstract = {BACKGROUND: Because many picoplanktonic eukaryotic species cannot currently be maintained in culture, direct sequencing of PCR-amplified 18S ribosomal gene DNA fragments from filtered sea-water has been successfully used to investigate the astounding diversity of these organisms. The recognition of many novel planktonic organisms is thus based solely on their 18S rDNA sequence. However, a species delimited by its 18S rDNA sequence might contain many cryptic species, which are highly differentiated in their protein coding sequences.

PRINCIPAL FINDINGS: Here, we investigate the issue of species identification from one gene to the whole genome sequence. Using 52 whole genome DNA sequences, we estimated the global genetic divergence in protein coding genes between organisms from different lineages and compared this to their ribosomal gene sequence divergences. We show that this relationship between proteome divergence and 18S divergence is lineage dependent. Unicellular lineages have especially low 18S divergences relative to their protein sequence divergences, suggesting that 18S ribosomal genes are too conservative to assess planktonic eukaryotic diversity. We provide an explanation for this lineage dependency, which suggests that most species with large effective population sizes will show far less divergence in 18S than protein coding sequences.

CONCLUSIONS: There is therefore a trade-off between using genes that are easy to amplify in all species, but which by their nature are highly conserved and underestimate the true number of species, and using genes that give a better description of the number of species, but which are more difficult to amplify. We have shown that this trade-off differs between unicellular and multicellular organisms as a likely consequence of differences in effective population sizes. We anticipate that biodiversity of microbial eukaryotic species is underestimated and that numerous "cryptic species" will become discernable with the future acquisition of genomic and metagenomic sequences.}, } @article {pmid21326886, year = {2010}, author = {Teichmann, M and Dieci, G and Pascali, C and Boldina, G}, title = {General transcription factors and subunits of RNA polymerase III: Paralogs for promoter- and cell type-specific transcription in multicellular eukaryotes.}, journal = {Transcription}, volume = {1}, number = {3}, pages = {130-135}, pmid = {21326886}, issn = {2154-1272}, abstract = {In the course of evolution of multi-cellular eukaryotes, paralogs of general transcription factors and RNA polymerase subunits emerged. Paralogs of transcription factors and of the RPC32 subunit of RNA polymerase III play important roles in cell type- and promoter-specific transcription. Here we discuss their respective functions.}, } @article {pmid21325094, year = {2011}, author = {Kerner, P and Degnan, SM and Marchand, L and Degnan, BM and Vervoort, M}, title = {Evolution of RNA-binding proteins in animals: insights from genome-wide analysis in the sponge Amphimedon queenslandica.}, journal = {Molecular biology and evolution}, volume = {28}, number = {8}, pages = {2289-2303}, doi = {10.1093/molbev/msr046}, pmid = {21325094}, issn = {1537-1719}, mesh = {Amino Acid Motifs ; Animals ; Binding Sites/physiology ; *Evolution, Molecular ; *Genomics ; Humans ; Phylogeny ; Porifera/classification/*genetics ; Proteomics ; RNA-Binding Proteins/chemistry/*genetics ; }, abstract = {RNA-binding proteins (RBPs) are key players in various biological processes, most notably regulation of gene expression at the posttranscriptional level. Although many RBPs have been carefully studied in model organisms, very few studies have addressed the evolution of these proteins at the scale of the animal kingdom. We identified a large set of putative RBPs encoded by the genome of the demosponge Amphimedon queenslandica, a species representing a basal animal lineage. We compared the Amphimedon RBPs with those encoded by the genomes of two bilaterians (human and Drosophila), representatives of two other basal metazoan lineages (a placozoan and a cnidarian), a choanoflagellate (probable sister group of animals), and two fungi. We established the evolutionary history of 32 families of RBPs and found that most of the diversity of RBPs present in contemporary metazoans, including humans, was already established in the last common ancestor (LCA) of animals. This includes RBPs known to be involved in key processes in bilaterians, such as development, stem and/or germ cells properties, and noncoding RNA pathways. From this analysis, we infer that a complex toolkit of RBPs was present in the LCA of animals and that it has been recruited to perform new functions during early animal evolution, in particular in relation to the acquisition of multicellularity.}, } @article {pmid21320320, year = {2011}, author = {Schirrmeister, BE and Antonelli, A and Bagheri, HC}, title = {The origin of multicellularity in cyanobacteria.}, journal = {BMC evolutionary biology}, volume = {11}, number = {}, pages = {45}, pmid = {21320320}, issn = {1471-2148}, mesh = {Bayes Theorem ; *Biological Evolution ; Cyanobacteria/classification/*genetics ; DNA, Bacterial/genetics ; Likelihood Functions ; Models, Genetic ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Cyanobacteria are one of the oldest and morphologically most diverse prokaryotic phyla on our planet. The early development of an oxygen-containing atmosphere approximately 2.45-2.22 billion years ago is attributed to the photosynthetic activity of cyanobacteria. Furthermore, they are one of the few prokaryotic phyla where multicellularity has evolved. Understanding when and how multicellularity evolved in these ancient organisms would provide fundamental information on the early history of life and further our knowledge of complex life forms.

RESULTS: We conducted and compared phylogenetic analyses of 16S rDNA sequences from a large sample of taxa representing the morphological and genetic diversity of cyanobacteria. We reconstructed ancestral character states on 10,000 phylogenetic trees. The results suggest that the majority of extant cyanobacteria descend from multicellular ancestors. Reversals to unicellularity occurred at least 5 times. Multicellularity was established again at least once within a single-celled clade. Comparison to the fossil record supports an early origin of multicellularity, possibly as early as the "Great Oxygenation Event" that occurred 2.45-2.22 billion years ago.

CONCLUSIONS: The results indicate that a multicellular morphotype evolved early in the cyanobacterial lineage and was regained at least once after a previous loss. Most of the morphological diversity exhibited in cyanobacteria today--including the majority of single-celled species--arose from ancient multicellular lineages. Multicellularity could have conferred a considerable advantage for exploring new niches and hence facilitated the diversification of new lineages.}, } @article {pmid21318400, year = {2011}, author = {Gurkan, UA and Kishore, V and Condon, KW and Bellido, TM and Akkus, O}, title = {A scaffold-free multicellular three-dimensional in vitro model of osteogenesis.}, journal = {Calcified tissue international}, volume = {88}, number = {5}, pages = {388-401}, pmid = {21318400}, issn = {1432-0827}, support = {R01 DK076007/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bone Marrow Cells/*cytology/*physiology/ultrastructure ; Cell Culture Techniques ; Cells, Cultured ; Flow Cytometry ; Immunohistochemistry ; Male ; Microscopy, Electron ; Models, Animal ; *Models, Biological ; Osteogenesis/*physiology ; Rats ; Rats, Long-Evans ; Spectrometry, X-Ray Emission ; Spectrum Analysis, Raman ; }, abstract = {In vitro models of osteogenesis are essential for investigating bone biology and the effects of pharmaceutical, chemical, and physical cues on bone formation. Osteogenesis takes place in a complex three-dimensional (3D) environment with cells from both mesenchymal and hematopoietic origins. Existing in vitro models of osteogenesis include two-dimensional (2D) single type cell monolayers and 3D cultures. However, an in vitro scaffold-free multicellular 3D model of osteogenesis is missing. We hypothesized that the self-inductive ossification capacity of bone marrow tissue can be harnessed in vitro and employed as a scaffold-free multicellular 3D model of osteogenesis. Therefore, rat bone marrow tissue was cultured for 28 days in three settings: 2D monolayer, 3D homogenized pellet, and 3D organotypic explant. The ossification potential of marrow in each condition was quantified by micro-computed tomography. The 3D organotypic marrow explant culture resulted in the greatest level of ossification with plate-like bone formations (up to 5 mm in diameter and 0.24 mm in thickness). To evaluate the mimicry of the organotypic marrow explants to newly forming native bone tissue, detailed compositional and morphological analyses were performed, including characterization of the ossified matrix by histochemistry, immunohistochemistry, Raman microspectroscopy, energy dispersive X-ray spectroscopy, backscattered electron microscopy, and micromechanical tests. The results indicated that the 3D organotypic marrow explant culture model mimics newly forming native bone tissue in terms of the characteristics studied. Therefore, this platform holds significant potential to be used as a model of osteogenesis, offering an alternative to in vitro monolayer cultures and in vivo animal models.}, } @article {pmid21306451, year = {2012}, author = {Kato, N and Narutomi, K and Fukase, M and Motoyama, T}, title = {Hollow spheroids in ascites of ovarian clear cell carcinoma: how are they formed and how do they behave?.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {23}, number = {2}, pages = {120-125}, doi = {10.1111/j.1365-2303.2011.00847.x}, pmid = {21306451}, issn = {1365-2303}, mesh = {Adenocarcinoma, Clear Cell/*pathology ; Animals ; Ascites/*pathology ; Biological Specimen Banks ; Cytological Techniques ; Female ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Ovarian Neoplasms/*pathology ; Spheroids, Cellular/*pathology ; Suspensions ; Tumor Cells, Cultured ; }, abstract = {OBJECTIVE: Although the multicellular aggregates (spheroids) in malignant ascites are usually solid throughout, they sometimes have acellular hollow spaces, especially in ascites of ovarian clear cell carcinoma. The purpose of this study is to analyse the origin and behaviour of hollow spheroids.

METHODS: Archival cytological and histological specimens of 32 ovarian carcinomas, including 12 clear cell carcinomas, were reviewed. HAC-2, a clear cell carcinoma cell line, was injected into the abdominal cavity of nude mice for direct comparison of ascitic cytology and tumour histology. Spheroids that were collected from nude mice ascites were cultured in vitro to observe their behaviour.

RESULTS: Five of six clear cell carcinomas with hollow spheroids showed spherule-like hyaluronan-rich stroma in their tumour tissue, whereas those without hollow spheroids did not. After heterotransplantation, both ascites and tumour imprints showed small or large hollow spheroids. Hyaluronan was detected in the former but not in the latter. The abdominal tumours showed compact spherule-like hyaluronan-rich stroma, enlarged oedematous stroma or intermediate stroma. In both size and hyaluronan status, small and large hollow spheroids were approximately comparable to spherule-like hyaluronan-rich stroma and oedematous stroma, respectively. During culture in vitro, hollow spheroids were maintained as hollow spheroids in suspension, and produced daughter hollow spheroids.

CONCLUSIONS: The hollow space in the spheroids originates from spherule-like hyaluronan-rich stroma, where water trapping by hyaluronan causes enlargement of the space. The matrix within the hollow space serves as a scaffold that regulates cell polarity and matrix production.}, } @article {pmid21301472, year = {2011}, author = {Foster, KR}, title = {The sociobiology of molecular systems.}, journal = {Nature reviews. Genetics}, volume = {12}, number = {3}, pages = {193-203}, pmid = {21301472}, issn = {1471-0064}, support = {242670/ERC_/European Research Council/International ; }, mesh = {Animals ; *Biological Evolution ; *Competitive Behavior ; *Cooperative Behavior ; Female ; Genetic Association Studies ; Genetic Variation ; Humans ; Male ; Metabolic Networks and Pathways/genetics ; *Selection, Genetic ; *Sociobiology ; }, abstract = {It is often assumed that molecular systems are designed to maximize the competitive ability of the organism that carries them. In reality, natural selection acts on both cooperative and competitive phenotypes, across multiple scales of biological organization. Here I ask how the potential for social effects in evolution has influenced molecular systems. I discuss a range of phenotypes, from the selfish genetic elements that disrupt genomes, through metabolism, multicellularity and cancer, to behaviour and the organization of animal societies. I argue that the balance between cooperative and competitive evolution has shaped both form and function at the molecular scale.}, } @article {pmid21301065, year = {2011}, author = {Davies, PC and Lineweaver, CH}, title = {Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors.}, journal = {Physical biology}, volume = {8}, number = {1}, pages = {015001}, pmid = {21301065}, issn = {1478-3975}, support = {U54 CA143862-02/CA/NCI NIH HHS/United States ; U54 CA143682/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Evolution, Molecular ; Genes ; Humans ; Neoplasms/*genetics ; Phylogeny ; }, abstract = {The genes of cellular cooperation that evolved with multicellularity about a billion years ago are the same genes that malfunction to cause cancer. We hypothesize that cancer is an atavistic condition that occurs when genetic or epigenetic malfunction unlocks an ancient 'toolkit' of pre-existing adaptations, re-establishing the dominance of an earlier layer of genes that controlled loose-knit colonies of only partially differentiated cells, similar to tumors. The existence of such a toolkit implies that the progress of the neoplasm in the host organism differs distinctively from normal Darwinian evolution. Comparative genomics and the phylogeny of basal metazoans, opisthokonta and basal multicellular eukaryotes should help identify the relevant genes and yield the order in which they evolved. This order will be a rough guide to the reverse order in which cancer develops, as mutations disrupt the genes of cellular cooperation. Our proposal is consistent with current understanding of cancer and explains the paradoxical rapidity with which cancer acquires a suite of mutually-supportive complex abilities. Finally we make several predictions and suggest ways to test this model.}, } @article {pmid21300429, year = {2011}, author = {Moncho-Amor, V and Galardi-Castilla, M and Perona, R and Sastre, L}, title = {The dual-specificity protein phosphatase MkpB, homologous to mammalian MKP phosphatases, is required for D. discoideum post-aggregative development and cisplatin response.}, journal = {Differentiation; research in biological diversity}, volume = {81}, number = {3}, pages = {199-207}, doi = {10.1016/j.diff.2011.01.004}, pmid = {21300429}, issn = {1432-0436}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Cisplatin/*pharmacology ; Dictyostelium/*drug effects/*enzymology/genetics/*physiology ; Dual-Specificity Phosphatases/classification/genetics/*metabolism ; Gene Expression/drug effects ; Humans ; Mitogen-Activated Protein Kinase Phosphatases/genetics/*metabolism ; Mitogen-Activated Protein Kinases/genetics/metabolism ; Phylogeny ; Protozoan Proteins/classification/genetics/*metabolism ; Signal Transduction/physiology ; }, abstract = {Dual-specificity protein phosphatases participate in signal transduction pathways inactivating mitogen-activated protein kinases (MAP kinases). These signaling pathways are of critical importance in the regulation of numerous biological processes, including cell proliferation, differentiation and development. The social ameba Dictyostelium discoideum harbors 14 genes coding for proteins containing regions very similar to the dual-specificity protein phosphatase domain. One of these genes, mkpB, additionally codes for a region similar to the Rhodanase domain, characteristic of animal MAP kinase-phosphatases, in its N-terminal region. Cells that over-express this gene show increased protein phosphatase activity. mkpB is expressed in D. discoideum ameba at growth but it is greatly induced at 12h of multicellular development. Although it is expressed in all the cells of developmental structures, mkpB mRNA is enriched in cells with a distribution typical of anterior-like cells. Cells that express a catalytically inactive mutant of MkpB grow and aggregate like wild-type cells but show a greatly impaired post-aggregative development. In addition, the expression of cell-type specific genes is very delayed, indicating that this protein plays an important role in cell differentiation and development. Cells expressing the MkpB catalytically inactive mutant show increased sensitivity to cisplatin, while cells over-expressing wild type MkpB, or MkpA, proteins or mutated in the MAP kinase erkB gene are more resistant to this chemotherapeutic drug, as also shown in human tumor cells.}, } @article {pmid21297636, year = {2011}, author = {Costas, C and de la Paz Sanchez, M and Stroud, H and Yu, Y and Oliveros, JC and Feng, S and Benguria, A and López-Vidriero, I and Zhang, X and Solano, R and Jacobsen, SE and Gutierrez, C}, title = {Genome-wide mapping of Arabidopsis thaliana origins of DNA replication and their associated epigenetic marks.}, journal = {Nature structural & molecular biology}, volume = {18}, number = {3}, pages = {395-400}, pmid = {21297636}, issn = {1545-9985}, support = {R37 GM060398/GM/NIGMS NIH HHS/United States ; R37 GM060398-10/GM/NIGMS NIH HHS/United States ; /HHMI_/Howard Hughes Medical Institute/United States ; R01 GM060398/GM/NIGMS NIH HHS/United States ; GM60398/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Cell Cycle Proteins/metabolism ; Chromatin/metabolism ; *Chromosome Mapping ; *DNA Replication ; DNA, Plant/*genetics ; Epigenomics ; Histones/genetics ; Origin Recognition Complex/metabolism ; Protein Binding ; *Replication Origin ; }, abstract = {Genome integrity requires faithful chromosome duplication. Origins of replication, the genomic sites at which DNA replication initiates, are scattered throughout the genome. Their mapping at a genomic scale in multicellular organisms has been challenging. In this study we profiled origins in Arabidopsis thaliana by high-throughput sequencing of newly synthesized DNA and identified ~1,500 putative origins genome-wide. This was supported by chromatin immunoprecipitation and microarray (ChIP-chip) experiments to identify ORC1- and CDC6-binding sites. We validated origin activity independently by measuring the abundance of nascent DNA strands. The midpoints of most A. thaliana origin regions are preferentially located within the 5' half of genes, enriched in G+C, histone H2A.Z, H3K4me2, H3K4me3 and H4K5ac, and depleted in H3K4me1 and H3K9me2. Our data help clarify the epigenetic specification of DNA replication origins in A. thaliana and have implications for other eukaryotes.}, } @article {pmid21296451, year = {2011}, author = {Caulin, AF and Maley, CC}, title = {Peto's Paradox: evolution's prescription for cancer prevention.}, journal = {Trends in ecology & evolution}, volume = {26}, number = {4}, pages = {175-182}, pmid = {21296451}, issn = {0169-5347}, support = {R01 CA140657-03/CA/NCI NIH HHS/United States ; P30 CA010815/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R03 CA137811/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; R01 CA119224/CA/NCI NIH HHS/United States ; R03 CA137811-02/CA/NCI NIH HHS/United States ; P01 CA91955/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Body Size/*genetics ; Cell Transformation, Neoplastic/*genetics ; *Evolution, Molecular ; Humans ; Selection, Genetic ; }, abstract = {The evolution of multicellularity required the suppression of cancer. If every cell has some chance of becoming cancerous, large, long-lived organisms should have an increased risk of developing cancer compared with small, short-lived organisms. The lack of correlation between body size and cancer risk is known as Peto's paradox. Animals with 1000 times more cells than humans do not exhibit an increased cancer risk, suggesting that natural mechanisms can suppress cancer 1000 times more effectively than is done in human cells. Because cancer has proven difficult to cure, attention has turned to cancer prevention. In this review, similar to pharmaceutical companies mining natural products, we seek to understand how evolution has suppressed cancer to develop ultimately improved cancer prevention in humans.}, } @article {pmid21296155, year = {2011}, author = {Wang, Y and Sumathipala, N and Rayaprolu, S and Jiang, H}, title = {Recognition of microbial molecular patterns and stimulation of prophenoloxidase activation by a β-1,3-glucanase-related protein in Manduca sexta larval plasma.}, journal = {Insect biochemistry and molecular biology}, volume = {41}, number = {5}, pages = {322-331}, pmid = {21296155}, issn = {1879-0240}, support = {R01 GM058634/GM/NIGMS NIH HHS/United States ; R01 GM058634-13/GM/NIGMS NIH HHS/United States ; GM58634/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Catechol Oxidase/genetics/*metabolism ; Enzyme Activation ; Enzyme Precursors/genetics/*metabolism ; Gene Expression ; Glucan 1,3-beta-Glucosidase/genetics/*metabolism ; Hemocytes/metabolism ; Insect Proteins/genetics/*metabolism ; Isoenzymes/genetics/*metabolism ; Larva/genetics/immunology/metabolism ; Manduca/genetics/immunology/*metabolism ; Micrococcus luteus ; Molecular Sequence Data ; Phylogeny ; Polysaccharides, Bacterial/immunology/*metabolism ; Protein Binding ; RNA, Messenger/analysis/biosynthesis ; Sequence Alignment ; beta-Glucans/metabolism ; }, abstract = {Detection of pathogenic invaders is the essential first step of a successful defense response in multicellular organisms. In this study, we have identified a new member of the β-1,3-glucanase-related protein superfamily from the tobacco hornworm Manduca sexta. This protein, designated microbe binding protein (MBP), is 61% identical in sequence to Bombyx mori Gram-negative bacteria binding protein, but only 34-36% identical to M. sexta β-1,3-glucan recognition protein-1 and 2. Its mRNA levels were strongly up-regulated in hemocytes and fat body of immune challenged larvae, along with an increase in concentration of the plasma protein. We expressed M. sexta MBP in a baculovirus-insect cell system. The purified protein associated with intact bacteria and fungi. It specifically bound to lipoteichoic acid, lipopolysaccharide, diaminopimelic acid-type peptidoglycans (DAP-PGs) from Escherichia coli and Bacillus subtilis, but less so to laminarin or Lys-type PG from Staphylococcus aureus. The complex binding pattern was influenced by other plasma factors and additional microbial surface molecules. After different amounts of MBP had been incubated with larval plasma on ice, a concentration-dependent increase in phenoloxidase (PO) activity occurred in the absence of any microbial elicitor. The activity increase was also observed in the mixture of plasma and a bacterial or fungal cell wall component. The prophenoloxidase (proPO) activation became more prominent when DAP-PGs, Micrococcus luteus Lys-PG, or lipoteichoic acid was included in the mixture of MBP and plasma. Statistic analysis suggested that a synergistic enhancement of proPO activation was caused by an interaction between MBP and these elicitors, but not S. aureus Lys-PG, lipopolysaccharide, curdlan, or laminarin. These data indicate that M. sexta MBP is a component of the surveillance mechanism and, by working together with other pattern recognition molecules and serine proteinases, triggers the proPO activation system.}, } @article {pmid21295484, year = {2011}, author = {Lipinski, KJ and Farslow, JC and Fitzpatrick, KA and Lynch, M and Katju, V and Bergthorsson, U}, title = {High spontaneous rate of gene duplication in Caenorhabditis elegans.}, journal = {Current biology : CB}, volume = {21}, number = {4}, pages = {306-310}, pmid = {21295484}, issn = {1879-0445}, support = {P20 RR018754-06A1/RR/NCRR NIH HHS/United States ; P20 RR018754/RR/NCRR NIH HHS/United States ; R01-GM036827/GM/NIGMS NIH HHS/United States ; P20-RR18754/RR/NCRR NIH HHS/United States ; R01 GM036827/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Caenorhabditis elegans/*genetics ; Chromosome Mapping ; Gene Deletion ; Gene Duplication/*genetics ; Gene Expression Regulation ; Genes, Duplicate ; }, abstract = {Gene and genome duplications are the primary source of new genes and novel functions and have played a pivotal role in the evolution of genomic and organismal complexity. The spontaneous rate of gene duplication is a critical parameter for understanding the evolutionary dynamics of gene duplicates; yet few direct empirical estimates exist and differ widely. The presence of a large population of recently derived gene duplicates in sequenced genomes suggests a high rate of spontaneous origin, also evidenced by population genomic studies reporting rampant copy-number polymorphism at the intraspecific level. An analysis of long-term mutation accumulation lines of Caenorhabditis elegans for gene copy-number changes with array comparative genomic hybridization yields the first direct estimate of the genome-wide rate of gene duplication in a multicellular eukaryote. The gene duplication rate in C. elegans is quite high, on the order of 10(-7) duplications/gene/generation. This rate is two orders of magnitude greater than the spontaneous rate of point mutation per nucleotide site in this species and also greatly exceeds an earlier estimate derived from the frequency distribution of extant gene duplicates in the sequenced C. elegans genome.}, } @article {pmid21290306, year = {2011}, author = {Wolstenholme, AJ and Williamson, SM and Reaves, BJ}, title = {TRP channels in parasites.}, journal = {Advances in experimental medicine and biology}, volume = {704}, number = {}, pages = {359-371}, doi = {10.1007/978-94-007-0265-3_20}, pmid = {21290306}, issn = {0065-2598}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Parasites/*metabolism ; Transient Receptor Potential Channels/genetics/*metabolism ; }, abstract = {A wide range of single- and multi-cellular parasites infect humans and other animals, causing some of the most prevalent and debilitating diseases on the planet. There have been virtually no published studies on the TRP channels of this diverse group of organisms. However, since many parasite genomes have been sequenced, it is simple to demonstrate that they are present in all parasitic metazoans and that sequences related to the yeast trp are present in many protozoans, including all the kinetoplastids. We compared the TRP genes of three species of animal and plant parasitic nematode to those of C. elegans and found that the parasitic species all had fewer such genes. These differences may reflect the phylogenetic distance between the species studied, or may be due to loss of specific gene functions following the evolution of the parasitic lifestyle. Other helminth groups, the trematodes and cestodes, seem to possess many TRPC and TRPM genes, but lack TRPV and TRPN. Most ectoparasites are insects or arachnids. We compared the TRP genes of a plant parasitic aphid and an animal parasite louse and tick with those of Drosophila. Again, all the parasitic species seemed to have fewer types of TRP channel, though the difference was less marked than for the nematodes. The aphid lacks TRPP and TRPML channel genes, whereas the tick lacked those encoding TRPVs. Again, these differences may reflect adaptation to parasitism, and could enable TRP channels to be targeted in the development of novel antiparasitic drugs.}, } @article {pmid21285032, year = {2011}, author = {Price, N and Cartwright, RA and Sabath, N and Graur, D and Azevedo, RB}, title = {Neutral evolution of robustness in Drosophila microRNA precursors.}, journal = {Molecular biology and evolution}, volume = {28}, number = {7}, pages = {2115-2123}, pmid = {21285032}, issn = {1537-1719}, support = {R01 LM010009/LM/NLM NIH HHS/United States ; LM010009-01/LM/NLM NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; Computer Simulation ; Drosophila/*genetics ; *Evolution, Molecular ; MicroRNAs/*genetics ; Mutation ; Nucleic Acid Conformation ; *Penetrance ; Phylogeny ; Selection, Genetic ; Statistics, Nonparametric ; }, abstract = {Mutational robustness describes the extent to which a phenotype remains unchanged in the face of mutations. Theory predicts that the strength of direct selection for mutational robustness is at most the magnitude of the rate of deleterious mutation. As far as nucleic acid sequences are concerned, only long sequences in organisms with high deleterious mutation rates and large population sizes are expected to evolve mutational robustness. Surprisingly, recent studies have concluded that molecules that meet none of these conditions--the microRNA precursors (pre-miRNAs) of multicellular eukaryotes--show signs of selection for mutational and/or environmental robustness. To resolve the apparent disagreement between theory and these studies, we have reconstructed the evolutionary history of Drosophila pre-miRNAs and compared the robustness of each sequence to that of its reconstructed ancestor. In addition, we "replayed the tape" of pre-miRNA evolution via simulation under different evolutionary assumptions and compared these alternative histories with the actual one. We found that Drosophila pre-miRNAs have evolved under strong purifying selection against changes in secondary structure. Contrary to earlier claims, there is no evidence that these RNAs have been shaped by either direct or congruent selection for any kind of robustness. Instead, the high robustness of Drosophila pre-miRNAs appears to be mostly intrinsic and likely a consequence of selection for functional structures.}, } @article {pmid21282709, year = {2011}, author = {Swanson, WJ and Aagaard, JE and Vacquier, VD and Monné, M and Sadat Al Hosseini, H and Jovine, L}, title = {The molecular basis of sex: linking yeast to human.}, journal = {Molecular biology and evolution}, volume = {28}, number = {7}, pages = {1963-1966}, pmid = {21282709}, issn = {1537-1719}, support = {HD057974/HD/NICHD NIH HHS/United States ; HD 054631/HD/NICHD NIH HHS/United States ; R03 HD054631/HD/NICHD NIH HHS/United States ; R01 HD057974/HD/NICHD NIH HHS/United States ; HD042563/HD/NICHD NIH HHS/United States ; HD12986/HD/NICHD NIH HHS/United States ; R01 HD042563/HD/NICHD NIH HHS/United States ; 260759/ERC_/European Research Council/International ; R37 HD012986/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Egg Proteins/chemistry ; Evolution, Molecular ; Genes, Mating Type, Fungal ; Humans ; Models, Molecular ; Mollusca ; Protein Conformation ; Species Specificity ; Sperm-Ovum Interactions/*physiology ; Zona Pellucida/chemistry ; }, abstract = {Species-specific recognition between egg and sperm, a crucial event that marks the beginning of fertilization in multicellular organisms, mirrors the binding between haploid cells of opposite mating type in unicellular eukaryotes such as yeast. However, as implied by the lack of sequence similarity between sperm-binding regions of invertebrate and vertebrate egg coat proteins, these interactions are thought to rely on completely different molecular entities. Here, we argue that these recognition systems are, in fact, related: despite being separated by 0.6-1 billion years of evolution, functionally essential domains of a mollusc sperm receptor and a yeast mating protein adopt the same 3D fold as egg zona pellucida proteins mediating the binding between gametes in humans.}, } @article {pmid21278082, year = {2011}, author = {Meisch, F and Prioleau, MN}, title = {Genomic approaches to the initiation of DNA replication and chromatin structure reveal a complex relationship.}, journal = {Briefings in functional genomics}, volume = {10}, number = {1}, pages = {30-36}, pmid = {21278082}, issn = {2041-2657}, mesh = {Animals ; Chromatin/*chemistry/genetics ; DNA Replication/*genetics ; Genomics/*methods ; Nucleosomes/genetics ; Replication Origin/genetics ; Vertebrates/genetics ; }, abstract = {The mechanisms regulating the coordinate activation of tens of thousands of replication origins in multicellular organisms remain poorly explored. Recent advances in genomics have provided valuable information about the sites at which DNA replication is initiated and the selection mechanisms of specific sites in both yeast and vertebrates. Studies in yeast have advanced to the point that it is now possible to develop convincing models for origin selection. A general model has emerged, but yeast data have also revealed an unsuspected diversity of strategies for origin positioning. We focus here on the ways in which chromatin structure may affect the formation of pre-replication complexes, a prerequisite for origin activation. We also discuss the need to exercise caution when trying to extrapolate yeast models directly to more complex vertebrate genomes.}, } @article {pmid21275904, year = {2011}, author = {Vincensini, L and Blisnick, T and Bastin, P}, title = {1001 model organisms to study cilia and flagella.}, journal = {Biology of the cell}, volume = {103}, number = {3}, pages = {109-130}, doi = {10.1042/BC20100104}, pmid = {21275904}, issn = {1768-322X}, mesh = {Animals ; Cell Movement/genetics ; Cilia/*metabolism ; Ciliary Motility Disorders/metabolism ; Flagella/*metabolism ; Mice ; Models, Biological ; Signal Transduction ; }, abstract = {Most mammalian cell types have the potential to assemble at least one cilium. Immotile cilia participate in numerous sensing processes, while motile cilia are involved in cell motility and movement of extracellular fluid. The functional importance of cilia and flagella is highlighted by the growing list of diseases due to cilia defects. These ciliopathies are marked by an amazing diversity of clinical manifestations and an often complex genetic aetiology. To understand these pathologies, a precise comprehension of the biology of cilia and flagella is required. These organelles are remarkably well conserved throughout eukaryotic evolution. In this review, we describe the strengths of various model organisms to decipher diverse aspects of cilia and flagella biology: molecular composition, mode of assembly, sensing and motility mechanisms and functions. Pioneering studies carried out in the green alga Chlamydomonas established the link between cilia and several genetic diseases. Moreover, multicellular organisms such as mouse, zebrafish, Xenopus, Caenorhabditis elegans or Drosophila, and protists such as Paramecium, Tetrahymena and Trypanosoma or Leishmania each bring specific advantages to the study of cilium biology. For example, the function of genes involved in primary ciliary dyskinesia (due to defects in ciliary motility) can be efficiently assessed in trypanosomes.}, } @article {pmid21272359, year = {2011}, author = {Kalla, SE and Queller, DC and Lasagni, A and Strassmann, JE}, title = {Kin discrimination and possible cryptic species in the social amoeba Polysphondylium violaceum.}, journal = {BMC evolutionary biology}, volume = {11}, number = {}, pages = {31}, pmid = {21272359}, issn = {1471-2148}, mesh = {Dictyosteliida/classification/genetics/isolation & purification/*physiology ; Genetic Variation ; Molecular Sequence Data ; Phylogeny ; }, abstract = {BACKGROUND: The genetic diversity of many protists is unknown. The differences that result from this diversity can be important in interactions among individuals. The social amoeba Polysphondylium violaceum, which is a member of the Dictyostelia, has a social stage where individual amoebae aggregate together to form a multicellular fruiting body with dead stalk cells and live spores. Individuals can either cooperate with amoebae from the same clone, or sort to form clonal fruiting bodies. In this study we look at genetic diversity in P. violaceum and at how this diversity impacts social behavior.

RESULTS: The phylogeny of the ribosomal DNA sequence (17S to 5.8S region) shows that P. violaceum is made up of at least two groups. Mating compatibility is more common between clones from the same phylogenetic group, though matings between clones from different phylogenetic groups sometimes occurred. P. violaceum clones are more likely to form clonal fruiting bodies when they are mixed with clones from a different group than when they are mixed with a clone of the same group.

CONCLUSION: Both the phylogenetic and mating analyses suggest the possibility of cryptic species in P. violaceum. The level of divergence found within P. violaceum is comparable to the divergence between sibling species in other dictyostelids. Both major groups A/B and C/D/E/F show kin discrimination, which elevates relatedness within fruiting bodies but not to the level of clonality. The diminished cooperation in mixes between groups suggests that the level of genetic variation between individuals influences the extent of their cooperation.}, } @article {pmid21267464, year = {2011}, author = {Bridier, A and Le Coq, D and Dubois-Brissonnet, F and Thomas, V and Aymerich, S and Briandet, R}, title = {The spatial architecture of Bacillus subtilis biofilms deciphered using a surface-associated model and in situ imaging.}, journal = {PloS one}, volume = {6}, number = {1}, pages = {e16177}, pmid = {21267464}, issn = {1932-6203}, mesh = {Bacillus subtilis/genetics/*growth & development ; Biofilms/*growth & development ; Microscopy, Confocal ; Mutation ; Surface Properties ; }, abstract = {The formation of multicellular communities known as biofilms is the part of bacterial life cycle in which bacteria display cooperative behaviour and differentiated phenotypes leading to specific functions. Bacillus subtilis is a Gram-positive bacterium that has served for a decade as a model to study the molecular pathways that control biofilm formation. Most of the data on B. subtilis biofilms have come from studies on the formation of pellicles at the air-liquid interface, or on the complex macrocolonies that develop on semi-solid nutritive agar. Here, using confocal laser scanning microcopy, we show that B. subtilis strains of different origins are capable of forming biofilms on immersed surfaces with dramatically protruding "beanstalk-like" structures with certain strains. Indeed, these structures can reach a height of more than 300 µm with one undomesticated strain from a medical environment. Using 14 GFP-labeled mutants previously described as affecting pellicle or complex colony formation, we have identified four genes whose inactivation significantly impeded immersed biofilm development, and one mutation triggering hyperbiofilm formation. We also identified mutations causing the three-dimensional architecture of the biofilm to be altered. Taken together, our results reveal that B. subtilis is able to form specific biofilm features on immersed surfaces, and that the development of these multicellular surface-associated communities involves regulation pathways that are common to those governing the formation of pellicle and/or complex colonies, and also some specific mechanisms. Finally, we propose the submerged surface-associated biofilm as another relevant model for the study of B. subtilis multicellular communities.}, } @article {pmid21264374, year = {2011}, author = {Nanjundiah, V and Sathe, S}, title = {Social selection and the evolution of cooperative groups: the example of the cellular slime moulds.}, journal = {Integrative biology : quantitative biosciences from nano to macro}, volume = {3}, number = {4}, pages = {329-342}, doi = {10.1039/c0ib00115e}, pmid = {21264374}, issn = {1757-9708}, mesh = {*Biological Evolution ; Cell Aggregation/*physiology ; Cell Communication/physiology ; Dictyosteliida/*physiology ; Genotype ; Phenotype ; Selection, Genetic/*physiology ; Social Behavior ; Stress, Physiological/physiology ; }, abstract = {In social selection the phenotype of an individual depends on its own genotype as well as on the phenotypes, and so genotypes, of other individuals. This makes it impossible to associate an invariant phenotype with a genotype: the social context is crucial. Descriptions of metazoan development, which often is viewed as the acme of cooperative social behaviour, ignore or downplay this fact. The implicit justification for doing so is based on a group-selectionist point of view. Namely, embryos are clones, therefore all cells have the same evolutionary interest, and the visible differences between cells result from a common strategy. The reasoning is flawed, because phenotypic heterogeneity within groups can result from contingent choices made by cells from a flexible repertoire as in multicellular development. What makes that possible is phenotypic plasticity, namely the ability of a genotype to exhibit different phenotypes. However, co-operative social behaviour with division of labour requires that different phenotypes interact appropriately, not that they belong to the same genotype, or have overlapping genetic interests. We sketch a possible route to the evolution of social groups that involves many steps: (a) individuals that happen to be in spatial proximity benefit simply by virtue of their number; (b) traits that are already present act as preadaptations and improve the efficiency of the group; and (c) new adaptations evolve under selection in the social context--that is, via interactions between individuals--and further strengthen group behaviour. The Dictyostelid or cellular slime mould amoebae (CSMs) become multicellular in an unusual way, by the aggregation of free-living cells. In nature the resulting group can be genetically homogeneous (clonal) or heterogeneous (polyclonal); in either case its development, which displays strong cooperation between cells (to the extent of so-called altruism) is not affected. This makes the CSMs exemplars for the study of social behaviour.}, } @article {pmid21248150, year = {2011}, author = {Yoo, SK and Huttenlocher, A}, title = {Spatiotemporal photolabeling of neutrophil trafficking during inflammation in live zebrafish.}, journal = {Journal of leukocyte biology}, volume = {89}, number = {5}, pages = {661-667}, pmid = {21248150}, issn = {1938-3673}, support = {R01 GM074827/GM/NIGMS NIH HHS/United States ; GM074827/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Blotting, Western ; *Cell Movement ; *Disease Models, Animal ; Embryo, Nonmammalian/metabolism/radiation effects ; Image Processing, Computer-Assisted ; Inflammation/metabolism/*pathology ; *Light ; Luminescent Proteins/*chemistry/genetics/metabolism ; Neutrophils/*metabolism/pathology ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Wound Healing ; Zebrafish/growth & development/*metabolism ; }, abstract = {How neutrophils traffic during inflammation in vivo remains elusive. To visualize the origin and fate of neutrophils during induction and resolution of inflammation, we established a genetically encoded photolabeling system by generating transgenic zebrafish that express a photoconvertible fluorescent reporter Dendra2 in neutrophils. Spatiotemporal photolabeling of neutrophils in vivo demonstrates that they emerge from the hematopoietic tissue in close proximity to injured tissue and repeat forward and reverse migration between the wound and the vasculature. Subsequently, neutrophils disperse throughout the body as wound-healing proceeds, contributing to local resolution at injured tissue and systemic dissemination of wound-sensitized neutrophils. Tissue damage also alters the fate of neutrophils in the caudal hematopoietic tissue and promotes caudorostral mobilization of neutrophils via the circulation to the cephalic mesenchyme. This work provides new insight into neutrophil behaviors during inflammation and resolution within a multicellular organism.}, } @article {pmid21247747, year = {2011}, author = {Wittig, K and Kasper, J and Seipp, S and Leitz, T}, title = {Evidence for an instructive role of apoptosis during the metamorphosis of Hydractinia echinata (Hydrozoa).}, journal = {Zoology (Jena, Germany)}, volume = {114}, number = {1}, pages = {11-22}, doi = {10.1016/j.zool.2010.09.004}, pmid = {21247747}, issn = {1873-2720}, mesh = {Amino Acid Sequence ; Animals ; Apoptosis/*physiology ; Caspases/genetics/metabolism ; Conserved Sequence ; Gene Expression Profiling ; Gene Expression Regulation, Enzymologic ; Gene Knockdown Techniques ; Hydrozoa/enzymology/*growth & development ; *Metamorphosis, Biological ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; }, abstract = {Apoptosis is a highly conserved mechanism of cell deletion that destroys redundant, dysfunctional, damaged, and diseased cells. Furthermore, apoptotic cell death is essential during the development of multicellular organisms. However, there are only a few examples where the occurrence of apoptosis has been shown to be a direct prerequisite for developmental processes. As described previously by our group, the degradation of larval tissue during the first half of the metamorphosis of Hydractinia echinata involves extensive cell death. A large number of cells are removed, and we observed several cellular features of apoptotic cell death in the dying tissue, e.g., nucleosomal DNA fragmentation and nuclear condensation. Furthermore, we showed that metamorphosis in the basal cnidarian H. echinata depends on the activity of caspases, the central enzymes of apoptosis. In the present study, we build on these previous investigations of apoptosis in H. echinata by characterising a caspase-3 sequence in this species and placing it in an evolutionary context by performing phylogenetic analyses. Furthermore, we report the successful knockdown of a caspase by RNAi and show that apoptosis plays a role as an instructive mechanism in the metamorphosis of H. echinata.}, } @article {pmid21247453, year = {2011}, author = {Simões, MC and Lee, J and Djikeng, A and Cerqueira, GC and Zerlotini, A and da Silva-Pereira, RA and Dalby, AR and LoVerde, P and El-Sayed, NM and Oliveira, G}, title = {Identification of Schistosoma mansoni microRNAs.}, journal = {BMC genomics}, volume = {12}, number = {}, pages = {47}, pmid = {21247453}, issn = {1471-2164}, support = {U01 AI048828/AI/NIAID NIH HHS/United States ; 5D43TW007012-04/TW/FIC NIH HHS/United States ; U01-AI48828/AI/NIAID NIH HHS/United States ; D43TW006580/TW/FIC NIH HHS/United States ; }, mesh = {Animals ; Computational Biology ; Genome, Helminth/*genetics ; MicroRNAs/*genetics ; Schistosoma mansoni/*genetics ; }, abstract = {BACKGROUND: MicroRNAs (miRNAs) constitute a class of single-stranded RNAs which play a crucial role in regulating development and controlling gene expression by targeting mRNAs and triggering either translation repression or messenger RNA (mRNA) degradation. miRNAs are widespread in eukaryotes and to date over 14,000 miRNAs have been identified by computational and experimental approaches. Several miRNAs are highly conserved across species. In Schistosoma, the full set of miRNAs and their expression patterns during development remain poorly understood. Here we report on the development and implementation of a homology-based detection strategy to search for miRNA genes in Schistosoma mansoni. In addition, we report results on the experimental detection of miRNAs by means of cDNA cloning and sequencing of size-fractionated RNA samples.

RESULTS: Homology search using the high-throughput pipeline was performed with all known miRNAs in miRBase. A total of 6,211 mature miRNAs were used as reference sequences and 110 unique S. mansoni sequences were returned by BLASTn analysis. The existing mature miRNAs that produced these hits are reported, as well as the locations of the homologous sequences in the S. mansoni genome. All BLAST hits aligned with at least 95% of the miRNA sequence, resulting in alignment lengths of 19-24 nt. Following several filtering steps, 15 potential miRNA candidates were identified using this approach. By sequencing small RNA cDNA libraries from adult worm pairs, we identified 211 novel miRNA candidates in the S. mansoni genome. Northern blot analysis was used to detect the expression of the 30 most frequent sequenced miRNAs and to compare the expression level of these miRNAs between the lung stage schistosomula and adult worm stages. Expression of 11 novel miRNAs was confirmed by northern blot analysis and some presented a stage-regulated expression pattern. Three miRNAs previously identified from S. japonicum were also present in S. mansoni.

CONCLUSION: Evidence for the presence of miRNAs in S. mansoni is presented. The number of miRNAs detected by homology-based computational methods in S. mansoni is limited due to the lack of close relatives in the miRNA repository. In spite of this, the computational approach described here can likely be applied to the identification of pre-miRNA hairpins in other organisms. Construction and analysis of a small RNA library led to the experimental identification of 14 novel miRNAs from S. mansoni through a combination of molecular cloning, DNA sequencing and expression studies. Our results significantly expand the set of known miRNAs in multicellular parasites and provide a basis for understanding the structural and functional evolution of miRNAs in these metazoan parasites.}, } @article {pmid21243964, year = {2010}, author = {Folse, HJ and Roughgarden, J}, title = {What is an individual organism? A multilevel selection perspective.}, journal = {The Quarterly review of biology}, volume = {85}, number = {4}, pages = {447-472}, doi = {10.1086/656905}, pmid = {21243964}, issn = {0033-5770}, mesh = {Animals ; Behavior, Animal ; *Biological Evolution ; Genetic Heterogeneity ; Insecta/genetics ; Reproduction ; *Selection, Genetic ; Species Specificity ; }, abstract = {Most biologists implicitly define an individual organism as "one genome in one body." This definition is based on physiological and genetic criteria, but it is problematic for colonial organisms. We propose a definition based instead on the evolutionary criteria of alignment of fitness, export of fitness by germ-soma specialization, and adaptive functional organization. We consider how these concepts apply to various putative individual organisms. We conclude that complex multicellular organisms and colonies of eusocial insects satisfy these three criteria, but that, in most cases (with at least one notable exception), colonies of modular organisms and genetic chimeras do not. While species do not meet these criteria, they may meet the criteria for a broader concept--that of an evolutionary individual--and sexual reproduction may be a species-level exaptation for enhancing evolvability. We also review the costs and benefits of internal genetic heterogeneity within putative individuals, demonstrating that high relatedness is neither a necessary nor a sufficient condition for individuality, and that, in some cases, genetic variability may have adaptive benefits at the level of the whole.}, } @article {pmid21237625, year = {2011}, author = {Adamska, M and Degnan, BM and Green, K and Zwafink, C}, title = {What sponges can tell us about the evolution of developmental processes.}, journal = {Zoology (Jena, Germany)}, volume = {114}, number = {1}, pages = {1-10}, doi = {10.1016/j.zool.2010.10.003}, pmid = {21237625}, issn = {1873-2720}, mesh = {Animals ; *Biological Evolution ; Conserved Sequence ; Phylogeny ; Porifera/*classification/genetics/*growth & development ; Wnt Proteins/metabolism ; }, abstract = {Sponges are one of the simplest, and probably the oldest (earliest branching) multicellular lineage of extant animals. Although their embryonic development has been intensively studied in the late 19th and early 20th century, they have been mostly neglected by modern developmental biology. Recent interest in the evolution of development, aided by advances in sequencing technology, has brought the sponges back into the spotlight. It is known that the developmental toolkit of sponges includes signalling pathways, transcription factors and cell adhesion molecules that are employed during development of more complex animals (i.e. bilaterians). We are now beginning to understand how these conserved regulatory genes are used during the development of sponges. Methodological resources are now being developed for model species representing all major sponge lineages, potentially allowing us to gain insight into the evolutionary origin of animal developmental mechanisms.}, } @article {pmid21233006, year = {2011}, author = {Liu, Q and Gong, Z}, title = {The coupling of epigenome replication with DNA replication.}, journal = {Current opinion in plant biology}, volume = {14}, number = {2}, pages = {187-194}, doi = {10.1016/j.pbi.2010.12.001}, pmid = {21233006}, issn = {1879-0356}, mesh = {Chromatin/genetics ; DNA Methylation ; *DNA Replication ; *Epigenesis, Genetic ; *Genome, Plant ; Heterochromatin/genetics ; Histones/metabolism ; Models, Genetic ; Plants/*genetics ; Replication Origin ; S Phase ; }, abstract = {In multicellular organisms, each cell contains the same DNA sequence, but with different epigenetic information that determines the cell specificity. Semi-conservative DNA replication faithfully copies the parental nucleotide sequence into two DNA daughter strands during each cell cycle. At the same time, epigenetic marks such as DNA methylation and histone modifications are either precisely transmitted to the daughter cells or dynamically changed during S-phase. Recent studies indicate that in each cell cycle, many DNA replication related proteins are involved in not only genomic but also epigenomic replication. Histone modification proteins, chromatin remodeling proteins, histone variants, and RNAs participate in the epigenomic replication during S-phase. As a consequence, epigenome replication is closely linked with DNA replication during S-phase.}, } @article {pmid21224886, year = {2011}, author = {Snijder, B and Pelkmans, L}, title = {Origins of regulated cell-to-cell variability.}, journal = {Nature reviews. Molecular cell biology}, volume = {12}, number = {2}, pages = {119-125}, pmid = {21224886}, issn = {1471-0080}, mesh = {Animals ; Eukaryotic Cells/*cytology/metabolism/virology ; Gene Expression Profiling ; Humans ; Prokaryotic Cells/*cytology/metabolism ; Single-Cell Analysis ; }, abstract = {Single-cell measurements and lineage-tracing experiments are revealing that phenotypic cell-to-cell variability is often the result of deterministic processes, despite the existence of intrinsic noise in molecular networks. In most cases, this determinism represents largely uncharacterized molecular regulatory mechanisms, which places the study of cell-to-cell variability in the realm of molecular cell biology. Further research in the field will be important to advance quantitative cell biology because it will provide new insights into the mechanisms by which cells coordinate their intracellular activities in the spatiotemporal context of the multicellular environment.}, } @article {pmid21205784, year = {2011}, author = {Schaap, P}, title = {Evolutionary crossroads in developmental biology: Dictyostelium discoideum.}, journal = {Development (Cambridge, England)}, volume = {138}, number = {3}, pages = {387-396}, pmid = {21205784}, issn = {1477-9129}, support = {BB/G020426/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Biological Evolution ; *Developmental Biology ; Dictyostelium/classification/cytology/*growth & development/*metabolism ; Models, Biological ; Phylogeny ; }, abstract = {Dictyostelium discoideum belongs to a group of multicellular life forms that can also exist for long periods as single cells. This ability to shift between uni- and multicellularity makes the group ideal for studying the genetic changes that occurred at the crossroads between uni- and multicellular life. In this Primer, I discuss the mechanisms that control multicellular development in Dictyostelium discoideum and reconstruct how some of these mechanisms evolved from a stress response in the unicellular ancestor.}, } @article {pmid21193547, year = {2011}, author = {Dubin, MJ and Kasten, S and Nellen, W}, title = {Characterization of the Dictyostelium homolog of chromatin binding protein DET1 suggests a conserved pathway regulating cell type specification and developmental plasticity.}, journal = {Eukaryotic cell}, volume = {10}, number = {3}, pages = {352-362}, pmid = {21193547}, issn = {1535-9786}, mesh = {Amino Acid Sequence ; Biological Evolution ; Chromatin/genetics/*metabolism ; Dictyostelium/chemistry/genetics/*growth & development/*metabolism ; Gene Expression Regulation, Developmental ; Humans ; Molecular Sequence Data ; Protein Binding ; Protein Structure, Tertiary ; Protozoan Proteins/*chemistry/genetics/*metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {DET1 (De-etiolated 1) is a chromatin binding protein involved in developmental regulation in both plants and animals. DET1 is largely restricted to multicellular eukaryotes, and here we report the characterization of a DET1 homolog from the social amoeba Dictyostelium discoideum. As in other species, Dictyostelium DET1 is nuclear localized. In contrast to other species, where it is an essential protein, loss of DET1 is nonlethal in Dictyostelium, although viability is significantly reduced. The phenotype of the det1(-) mutant is highly pleiotropic and results in a large degree of heterogeneity in developmental parameters. Loss of DET1 results in delayed and abnormal development with enlarged aggregation territories. Mutant slugs displayed cell type patterning with a bias toward the prestalk pathway. A number of DET1-interacting proteins are conserved in Dictyostelium, and the apparently conserved role of DET1 in regulatory pathways involving the bZIP transcription factors DimB, c-Jun, and HY5 suggests a highly conserved mechanism regulating development in multicellular eukaryotes. While the mechanism by which DET1 functions is unclear, it appears that it has a key role in regulation of developmental plasticity and integration of information on environmental conditions into the developmental program of an organism.}, } @article {pmid21190752, year = {2011}, author = {Butterfield, NJ}, title = {Animals and the invention of the Phanerozoic Earth system.}, journal = {Trends in ecology & evolution}, volume = {26}, number = {2}, pages = {81-87}, doi = {10.1016/j.tree.2010.11.012}, pmid = {21190752}, issn = {0169-5347}, mesh = {Animals ; *Biological Evolution ; *Ecosystem ; Paleontology ; }, abstract = {Animals do not just occupy the modern biosphere, they permeate its structure and define how it works. Their unique combination of organ-grade multicellularity, motility and heterotrophic habit makes them powerful geobiological agents, imposing myriad feedbacks on nutrient cycling, productivity and environment. Most significantly, animals have 'engineered' the biosphere over evolutionary time, forcing the diversification of, for example, phytoplankton, land plants, trophic structure, large body size, bioturbation, biomineralization and indeed the evolutionary process itself. This review surveys how animals contribute to the modern world and provides a basis for reconstructing ancient ecosystems. Earlier, less animal-influenced biospheres worked quite differently from the one currently occupied, with the Ediacaran-Cambrian radiation of organ-grade animals marking a fundamental shift in macroecological and macroevolutionary expression.}, } @article {pmid21190136, year = {2011}, author = {Gantt, E}, title = {Oxygenic photosynthesis and the distribution of chloroplasts.}, journal = {Photosynthesis research}, volume = {107}, number = {1}, pages = {1-6}, pmid = {21190136}, issn = {1573-5079}, mesh = {*Biological Evolution ; Chlorophyta/metabolism ; Chloroplasts/classification/genetics/*metabolism ; Cyanobacteria/*metabolism ; Glaucophyta/metabolism ; Models, Biological ; Oxygen/*metabolism ; *Photosynthesis/genetics ; Photosystem I Protein Complex/genetics ; Photosystem II Protein Complex/genetics ; Rhodophyta/metabolism ; Symbiosis ; Time Factors ; }, abstract = {The integrated functioning of two photosystems (I and II) whether in cyanobacteria or in chloroplasts is the outstanding sign of a common ancestral origin. Many variations on the basic theme are currently evident in oxygenic photosynthetic organisms whether they are prokaryotes, unicellular, or multicellular. By conservative estimates, oxygenic photosynthesis has been around for at least ca. 2.2-2.7 billions years, consistent with cyanobacteria-type microfossils, biomarkers, and an atmospheric rise in oxygen to less than 1.0% of the present concentration. The presumptions of chloroplast formation by the cyanobacterial uptake into a eukaryote prior to 1.6 BYa ago are confounded by assumptions of host type(s) and potential tolerance of oxygen toxicity. The attempted dating and interrelationships of particular chloroplasts in various plant or animal lineages has relied heavily on phylogenomic analysis and evaluations that have been difficult to confirm separately. Many variations occur in algal groups, involving the type and number of accessory pigments, and the number(s) of membranes (2-4) enclosing a chloroplast, which can both help and complicate inferences made about early or late origins of chloroplasts. Integration of updated phylogenomics with physiological and cytological observations remains a special challenge, but could lead to more accurate assumptions of initial and extant endosymbiotic event(s) leading toward stable chloroplast associations.}, } @article {pmid21188609, year = {2011}, author = {Wang, C and Zhang, C and Han, J and Wu, H and Fan, Y}, title = {Simulated evolution of the vertebral body based on basic multicellular unit activities.}, journal = {Journal of bone and mineral metabolism}, volume = {29}, number = {4}, pages = {466-476}, pmid = {21188609}, issn = {1435-5604}, mesh = {Aging/physiology ; Algorithms ; *Computer Simulation ; Elastic Modulus/physiology ; Humans ; Models, Anatomic ; Spine/*anatomy & histology/*cytology/growth & development ; Stress, Mechanical ; }, abstract = {A numerical model based on the theory of bone remodeling is proposed to predict the evolution of trabecular bone architecture within the vertebral body and to investigate the process of degeneration in vertebral bone. In this study, particular attention is paid on the description of microstructure changes during the aging process. To take into account the effect of basic multicellular units (BMUs), a set of computational algorithms has been developed. It is assumed that BMU activation probability depends on the state of damaged bone tissue (damage accumulation, ω), which is evaluated according to previous research concerning bone fatigue damage. Combining these algorithms with the finite-element method (FEM), the microstructure of vertebral bone has been predicted for up to 8 simulated years. Moreover, biomechanical material properties have been monitored to investigate the changes of vertebral bone with age. This study shows that the simulation based on BMU activities has the potential to define and predict the morphological evolution of the vertebral body. It can be concluded that the novel algorithms incorporating the coupled effects of both adaptive remodeling and microdamage remodeling could be utilized to gain greater insight into the mechanism of bone loss in the elderly population.}, } @article {pmid21187424, year = {2011}, author = {Johnson, ME and Hummer, G}, title = {Nonspecific binding limits the number of proteins in a cell and shapes their interaction networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {108}, number = {2}, pages = {603-608}, pmid = {21187424}, issn = {1091-6490}, support = {//Intramural NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans ; Fungal Proteins/chemistry ; Genome ; Humans ; Kinetics ; Models, Statistical ; Protein Binding ; *Protein Interaction Mapping ; Proteome ; Proteomics/methods ; Temperature ; Thermodynamics ; }, abstract = {Multicellular organisms, from Caenorhabditis elegans to humans, have roughly the same number of protein encoding genes. We show that the need to prevent disease-causing nonspecific interactions between proteins provides a simple physical reason why organism complexity is not reflected in the number of distinct proteins. By collective evolution of the amino acid sequences of protein binding interfaces we estimate the degree of misbinding as a function of the number of distinct proteins. Protein interaction energies are calculated with an empirical, residue-specific energy function tuned for protein binding. We show that the achievable energy gap favoring specific over nonspecific binding decreases with protein number in a power-law fashion. From the fraction of proteins involved in nonspecific complexes as a function of increasing protein number and decreasing energy gap, we predict the limits these binding requirements place on the number of different proteins that can function effectively in a given cellular compartment. Remarkably, the optimization of binding interfaces favors networks in which a few proteins have many partners, and most proteins have few partners, consistent with a scale-free network topology. We conclude that nonspecific binding adds to the evolutionary pressure to develop scale-free protein-protein interaction networks.}, } @article {pmid21177950, year = {2011}, author = {Rumpho, ME and Pelletreau, KN and Moustafa, A and Bhattacharya, D}, title = {The making of a photosynthetic animal.}, journal = {The Journal of experimental biology}, volume = {214}, number = {Pt 2}, pages = {303-311}, pmid = {21177950}, issn = {1477-9145}, support = {R01 ES013679/ES/NIEHS NIH HHS/United States ; T32 GM008629/GM/NIGMS NIH HHS/United States ; R01ES013679/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Chlorophyta/*genetics/metabolism ; Gene Expression Profiling ; *Gene Transfer, Horizontal ; Mollusca/*genetics/metabolism ; *Photosynthesis ; Plastids/genetics/metabolism ; *Symbiosis ; }, abstract = {Symbiotic animals containing green photobionts challenge the common perception that only plants are capable of capturing the sun's rays and converting them into biological energy through photoautotrophic CO(2) fixation (photosynthesis). 'Solar-powered' sacoglossan molluscs, or sea slugs, have taken this type of symbiotic association one step further by solely harboring the photosynthetic organelle, the plastid (=chloroplast). One such sea slug, Elysia chlorotica, lives as a 'plant' when provided with only light and air as a result of acquiring plastids during feeding on its algal prey Vaucheria litorea. The captured plastids (kleptoplasts) are retained intracellularly in cells lining the digestive diverticula of the sea slug, a phenomenon sometimes referred to as kleptoplasty. Photosynthesis by the plastids provides E. chlorotica with energy and fixed carbon for its entire lifespan of ~10 months. The plastids are not transmitted vertically (i.e. are absent in eggs) and do not undergo division in the sea slug. However, de novo protein synthesis continues, including plastid- and nuclear-encoded plastid-targeted proteins, despite the apparent absence of algal nuclei. Here we discuss current data and provide hypotheses to explain how long-term photosynthetic activity is maintained by the kleptoplasts. This fascinating 'green animal' provides a unique model to study the evolution of photosynthesis in a multicellular heterotrophic organism.}, } @article {pmid21174128, year = {2011}, author = {Hallmann, A}, title = {Evolution of reproductive development in the volvocine algae.}, journal = {Sexual plant reproduction}, volume = {24}, number = {2}, pages = {97-112}, pmid = {21174128}, issn = {1432-2145}, mesh = {*Biological Evolution ; Germ Cells/*growth & development ; Phylogeny ; Reproduction ; Volvox/classification/genetics/growth & development/*physiology ; }, abstract = {The evolution of multicellularity, the separation of germline cells from sterile somatic cells, and the generation of a male-female dichotomy are certainly among the greatest innovations of eukaryotes. Remarkably, phylogenetic analysis suggests that the shift from simple to complex, differentiated multicellularity was not a unique progression in the evolution of life, but in fact a quite frequent event. The spheroidal green alga Volvox and its close relatives, the volvocine algae, span the full range of organizational complexity, from unicellular and colonial genera to multicellular genera with a full germ-soma division of labor and male-female dichotomy; thus, these algae are ideal model organisms for addressing fundamental issues related to the transition to multicellularity and for discovering universal rules that characterize this transition. Of all living species, Volvox carteri represents the simplest version of an immortal germline producing specialized somatic cells. This cellular specialization involved the emergence of mortality and the production of the first dead ancestors in the evolution of this lineage. Volvocine algae therefore exemplify the evolution of cellular cooperation from cellular autonomy. They also serve as a prime example of the evolution of complex traits by a few successive, small steps. Thus, we learn from volvocine algae that the evolutionary transition to complex, multicellular life is probably much easier to achieve than is commonly believed.}, } @article {pmid21170032, year = {2011}, author = {Neukomm, LJ and Frei, AP and Cabello, J and Kinchen, JM and Zaidel-Bar, R and Ma, Z and Haney, LB and Hardin, J and Ravichandran, KS and Moreno, S and Hengartner, MO}, title = {Loss of the RhoGAP SRGP-1 promotes the clearance of dead and injured cells in Caenorhabditis elegans.}, journal = {Nature cell biology}, volume = {13}, number = {1}, pages = {79-86}, pmid = {21170032}, issn = {1476-4679}, support = {GM078747/GM/NIGMS NIH HHS/United States ; F32 GM078747/GM/NIGMS NIH HHS/United States ; T32 AI055432/AI/NIAID NIH HHS/United States ; R01 GM064709/GM/NIGMS NIH HHS/United States ; R01 GM058038/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; *Apoptosis ; Caenorhabditis elegans/genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cell Line ; GTPase-Activating Proteins/genetics/*metabolism ; Green Fluorescent Proteins/genetics/metabolism ; Mice ; Microscopy, Fluorescence ; Molecular Sequence Data ; Mutation ; NIH 3T3 Cells ; Phagocytosis ; Protein Binding ; RNA Interference ; Sequence Homology, Amino Acid ; rac GTP-Binding Proteins/genetics/metabolism ; }, abstract = {Multicellular animals rapidly clear dying cells from their bodies. Many of the pathways that mediate this cell removal are conserved through evolution. Here, we identify srgp-1 as a negative regulator of cell clearance in both Caenorhabditis elegans and mammalian cells. Loss of srgp-1 function results in improved engulfment of apoptotic cells, whereas srgp-1 overexpression inhibits apoptotic cell corpse removal. We show that SRGP-1 functions in engulfing cells and functions as a GTPase activating protein (GAP) for CED-10 (Rac1). Interestingly, loss of srgp-1 function promotes not only the clearance of already dead cells, but also the removal of cells that have been brought to the verge of death through sublethal apoptotic, necrotic or cytotoxic insults. In contrast, impaired engulfment allows damaged cells to escape clearance, which results in increased long-term survival. We propose that C. elegans uses the engulfment machinery as part of a primitive, but evolutionarily conserved, survey mechanism that identifies and removes unfit cells within a tissue.}, } @article {pmid21169416, year = {2011}, author = {Leondaritis, G and Sarri, T and Dafnis, I and Efstathiou, A and Galanopoulou, D}, title = {Biochemical and genetic evidence for the presence of multiple phosphatidylinositol- and phosphatidylinositol 4,5-bisphosphate-specific phospholipases C in Tetrahymena.}, journal = {Eukaryotic cell}, volume = {10}, number = {3}, pages = {412-422}, pmid = {21169416}, issn = {1535-9786}, mesh = {Amino Acid Sequence ; *Gene Expression Regulation, Enzymologic ; Molecular Sequence Data ; Phosphatidylinositols/metabolism ; Phosphoinositide Phospholipase C/chemistry/*genetics/*metabolism ; Phylogeny ; Sequence Alignment ; Tetrahymena/chemistry/classification/*enzymology/genetics ; }, abstract = {Eukaryotic phosphoinositide-specific phospholipases C (PI-PLC) specifically hydrolyze phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)], produce the Ca(2+)-mobilizing agent inositol 1,4,5-trisphosphate, and regulate signaling in multicellular organisms. Bacterial PtdIns-specific PLCs, also present in trypanosomes, hydrolyze PtdIns and glycosyl-PtdIns, and they are considered important virulence factors. All unicellular eukaryotes studied so far contain a single PI-PLC-like gene. In this report, we show that ciliates are an exception, since we provide evidence that Tetrahymena species contain two sets of functional genes coding for both bacterial and eukaryotic PLCs. Biochemical characterization revealed two PLC activities that differ in their phosphoinositide substrate utilization, subcellular localization, secretion to extracellular space, and sensitivity to Ca(2+). One of these activities was identified as a typical membrane-associated PI-PLC activated by low-micromolar Ca(2+), modestly activated by GTPγS in vitro, and inhibited by the compound U73122 [1-(6-{[17β-3-methoxyestra-1,3,5(10)-trien-17-yl]amino}hexyl)-1H-pyrrole-2,5-dione]. Importantly, inhibition of PI-PLC in vivo resulted in rapid upregulation of PtdIns(4,5)P(2) levels, suggesting its functional importance in regulating phosphoinositide turnover in Tetrahymena. By in silico and molecular analysis, we identified two PLC genes that exhibit significant similarity to bacterial but not trypanosomal PLC genes and three eukaryotic PI-PLC genes, one of which is a novel inactive PLC similar to proteins identified only in metazoa. Comparative studies of expression patterns and PI-PLC activities in three T. thermophila strains showed a correlation between expression levels and activity, suggesting that the three eukaryotic PI-PLC genes are functionally nonredundant. Our findings imply the presence of a conserved and elaborate PI-PLC-Ins(1,4,5)P(3)-Ca(2+) regulatory axis in ciliates.}, } @article {pmid21167904, year = {2011}, author = {Ogawa, K and Miyake, Y}, title = {Generation model of positional values as cell operation during the development of multicellular organisms.}, journal = {Bio Systems}, volume = {103}, number = {3}, pages = {400-409}, doi = {10.1016/j.biosystems.2010.12.002}, pmid = {21167904}, issn = {1872-8324}, mesh = {Animals ; Body Patterning ; DNA-Binding Proteins/genetics/metabolism ; Drosophila/*embryology/*metabolism ; Drosophila Proteins/genetics/metabolism ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/genetics/metabolism ; *Models, Biological ; Trans-Activators/genetics/metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {Many conventional models have used the positional information hypothesis to explain each elementary process of morphogenesis during the development of multicellular organisms. Their models assume that the steady concentration patterns of morphogens formed in an extracellular environment have an important property of positional information, so-called "robustness". However, recent experiments reported that a steady morphogen pattern, the concentration gradient of the Bicoid protein, during early Drosophila embryonic development is not robust for embryo-to-embryo variability. These reports encourage a reconsideration of a long-standing problem in systematic cell differentiation: what is the entity of positional information for cells? And, what is the origin of the robust boundary of gene expression? To address these problems at a cellular level, in this article we pay attention to the re-generative phenomena that show another important property of positional information, "size invariance". In view of regenerative phenomena, we propose a new mathematical model to describe the generation mechanism of a spatial pattern of positional values. In this model, the positional values are defined as the values into which differentiable cells transform a spatial pattern providing positional information. The model is mathematically described as an associative algebra composed of various terms, each of which is the multiplication of some fundamental operators under the assumption that the operators are derived from the remarkable properties of cell differentiation on an amputation surface in regenerative phenomena. We apply this model to the concentration pattern of the Bicoid protein during the anterior-posterior axis formation in Drosophila, and consider the conditions needed to establish the robust boundary of the expression of the hunchback gene.}, } @article {pmid21137109, year = {2010}, author = {Gatenby, RA and Gillies, RJ and Brown, JS}, title = {Evolutionary dynamics of cancer prevention.}, journal = {Nature reviews. Cancer}, volume = {10}, number = {8}, pages = {526-527}, pmid = {21137109}, issn = {1474-1768}, support = {R01 CA077575/CA/NCI NIH HHS/United States ; U54 CA143970/CA/NCI NIH HHS/United States ; NCI 1US4CA143970-01/CA/NCI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Cell Movement ; Cell Proliferation ; *Cell Transformation, Neoplastic ; Epithelium/*immunology ; Genetic Fitness ; Humans ; Mutation ; Neoplasms/pathology/*prevention & control ; *Stem Cells/physiology ; }, abstract = {Multicellular organisms must evolve mechanisms to suppress cancer formation prior to reproduction, and we propose that the organizational structure of normal epithelium is one such strategy. Understanding evolved host cancer suppression mechanisms is essential to defining the first steps of carcinogenesis and developing rational cancer prevention strategies.}, } @article {pmid21131095, year = {2011}, author = {Vlahou, G and Eliáš, M and von Kleist-Retzow, JC and Wiesner, RJ and Rivero, F}, title = {The Ras related GTPase Miro is not required for mitochondrial transport in Dictyostelium discoideum.}, journal = {European journal of cell biology}, volume = {90}, number = {4}, pages = {342-355}, doi = {10.1016/j.ejcb.2010.10.012}, pmid = {21131095}, issn = {1618-1298}, mesh = {Amino Acid Sequence ; Biological Evolution ; Biological Transport/genetics ; Calcium/metabolism ; Dictyostelium/*enzymology/genetics ; Glucose/metabolism ; Kinesins/genetics/metabolism ; Microtubules/genetics/metabolism ; Mitochondria/*enzymology ; Mitochondrial Membrane Transport Proteins/metabolism ; Molecular Sequence Data ; Oxygen Consumption ; Phylogeny ; rho GTP-Binding Proteins/classification/genetics/*metabolism ; }, abstract = {Ras-related GTPases of the Miro family have been implicated in mitochondrial homeostasis and microtubule-dependent transport. They consist of two GTP-binding domains separated by calcium-binding motifs and of a C-terminal transmembrane domain that targets the protein to the outer mitochondrial membrane. We disrupted the single Miro-encoding gene in Dictyostelium discoideum and observed a substantial growth defect that we attribute to a decreased mitochondrial mass and cellular ATP content. However, mutant cells even showed an increased rate of oxygen consumption, while glucose consumption, mitochondrial transmembrane potential and production of reactive oxygen species were unaltered. Processes characteristic of the multicellular stage of the D. discoideum life cycle were also unaltered. Although mitochondria occasionally use microtubules for transport in D. discoideum, their size and distribution were not visibly affected. We found Miro in all branches of the eukaryotic tree with the exception of a few protist lineages (mainly those lacking typical mitochondria). Trypanosomatids and ciliates possess structurally unique homologs lacking the N-terminal or the C-terminal GTPase domain, respectively. We propose that in D. discoideum, as in yeasts and plants, Miro plays roles in mitochondrial homeostasis, but the ability to build a complex that regulates its association to kinesin for microtubule-dependent transport probably arose in metazoans.}, } @article {pmid21124851, year = {2010}, author = {Usenik, A and Legiša, M}, title = {Evolution of allosteric citrate binding sites on 6-phosphofructo-1-kinase.}, journal = {PloS one}, volume = {5}, number = {11}, pages = {e15447}, pmid = {21124851}, issn = {1932-6203}, mesh = {Allosteric Site/genetics ; Amino Acid Sequence ; Amino Acid Substitution ; Binding Sites/genetics ; Biocatalysis/drug effects ; Citrates/*metabolism/pharmacology ; *Evolution, Molecular ; Humans ; Immunoblotting ; Kinetics ; Molecular Sequence Data ; *Mutation ; Phosphofructokinase-1/antagonists & inhibitors/*genetics/metabolism ; Recombinant Proteins/metabolism ; Sequence Homology, Amino Acid ; }, abstract = {As an important part of metabolism, metabolic flux through the glycolytic pathway is tightly regulated. The most complex control is exerted on 6-phosphofructo-1-kinase (PFK1) level; this control overrules the regulatory role of other allosteric enzymes. Among other effectors, citrate has been reported to play a vital role in the suppression of this enzyme's activity. In eukaryotes, amino acid residues forming the allosteric binding site for citrate are found both on the N- and the C-terminal region of the enzyme. These site has evolved from the phosphoenolpyruvate/ADP binding site of bacterial PFK1 due to the processes of duplication and tandem fusion of prokaryotic ancestor gene followed by the divergence of the catalytic and effector binding sites. Stricter inhibition of the PFK1 enzyme was needed during the evolution of multi-cellular organisms, and the most stringent control of PFK1 by citrate occurs in vertebrates. By substituting a single amino acid (K557R or K617A) as a component of the allosteric binding site in the C-terminal region of human muscle type PFK-M with a residue found in the corresponding site of a fungal enzyme, the inhibitory effect of citrate was attenuated. Moreover, the proteins carrying these single mutations enabled growth of E. coli transformants encoding mutated human PFK-M in a glucose-containing medium that did not support the growth of E. coli transformed with native human PFK-M. Substitution of another residue at the citrate-binding site (D591V) of human PFK-M resulted in the complete loss of activity. Detailed analyses revealed that the mutated PFK-M subunits formed dimers but were unable to associate into the active tetrameric holoenzyme. These results suggest that stricter control over glycolytic flux developed in metazoans, whose somatic cells are largely characterized by slow proliferation.}, } @article {pmid21123265, year = {2011}, author = {Jékely, G}, title = {Origin and early evolution of neural circuits for the control of ciliary locomotion.}, journal = {Proceedings. Biological sciences}, volume = {278}, number = {1707}, pages = {914-922}, pmid = {21123265}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; Cilia/*physiology ; Larva/anatomy & histology/physiology ; Muscle Contraction/physiology ; *Nerve Net ; Polychaeta/anatomy & histology/growth & development/*physiology ; }, abstract = {Behaviour evolved before nervous systems. Various single-celled eukaryotes (protists) and the ciliated larvae of sponges devoid of neurons can display sophisticated behaviours, including phototaxis, gravitaxis or chemotaxis. In single-celled eukaryotes, sensory inputs directly influence the motor behaviour of the cell. In swimming sponge larvae, sensory cells influence the activity of cilia on the same cell, thereby steering the multicellular larva. In these organisms, the efficiency of sensory-to-motor transformation (defined as the ratio of sensory cells to total cell number) is low. With the advent of neurons, signal amplification and fast, long-range communication between sensory and motor cells became possible. This may have first occurred in a ciliated swimming stage of the first eumetazoans. The first axons may have had en passant synaptic contacts to several ciliated cells to improve the efficiency of sensory-to-motor transformation, thereby allowing a reduction in the number of sensory cells tuned for the same input. This could have allowed the diversification of sensory modalities and of the behavioural repertoire. I propose that the first nervous systems consisted of combined sensory-motor neurons, directly translating sensory input into motor output on locomotor ciliated cells and steering muscle cells. Neuronal circuitry with low levels of integration has been retained in cnidarians and in the ciliated larvae of some marine invertebrates. This parallel processing stage could have been the starting point for the evolution of more integrated circuits performing the first complex computations such as persistence or coincidence detection. The sensory-motor nervous systems of cnidarians and ciliated larvae of diverse phyla show that brains, like all biological structures, are not irreducibly complex.}, } @article {pmid21118020, year = {2010}, author = {Doughty, CE and Wolf, A}, title = {Detecting tree-like multicellular life on extrasolar planets.}, journal = {Astrobiology}, volume = {10}, number = {9}, pages = {869-879}, doi = {10.1089/ast.2010.0495}, pmid = {21118020}, issn = {1557-8070}, mesh = {Astronomy ; Evolution, Planetary ; *Exobiology ; Extraterrestrial Environment ; *Models, Theoretical ; *Planets ; Spacecraft ; Water ; }, abstract = {Over the next two decades, NASA and ESA are planning a series of space-based observatories to find Earth-like planets and determine whether life exists on these planets. Previous studies have assessed the likelihood of detecting life through signs of biogenic gases in the atmosphere or a red edge. Biogenic gases and the red edge could be signs of either single-celled or multicellular life. In this study, we propose a technique with which to determine whether tree-like multicellular life exists on extrasolar planets. For multicellular photosynthetic organisms on Earth, competition for light and the need to transport water and nutrients has led to a tree-like body plan characterized by hierarchical branching networks. This design results in a distinct bidirectional reflectance distribution function (BRDF) that causes differing reflectance at different sun/view geometries. BRDF arises from the changing visibility of the shadows cast by objects, and the presence of tree-like structures is clearly distinguishable from flat ground with the same reflectance spectrum. We examined whether the BRDF could detect the existence of tree-like structures on an extrasolar planet by using changes in planetary albedo as a planet orbits its star. We used a semi-empirical BRDF model to simulate vegetation reflectance at different planetary phase angles and both simulated and real cloud cover to calculate disk and rotation-averaged planetary albedo for a vegetated and non-vegetated planet with abundant liquid water. We found that even if the entire planetary albedo were rendered to a single pixel, the rate of increase of albedo as a planet approaches full illumination would be comparatively greater on a vegetated planet than on a non-vegetated planet. Depending on how accurately planetary cloud cover can be resolved and the capabilities of the coronagraph to resolve exoplanets, this technique could theoretically detect tree-like multicellular life on exoplanets in 50 stellar systems.}, } @article {pmid21109780, year = {2011}, author = {Loenarz, C and Coleman, ML and Boleininger, A and Schierwater, B and Holland, PW and Ratcliffe, PJ and Schofield, CJ}, title = {The hypoxia-inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerens.}, journal = {EMBO reports}, volume = {12}, number = {1}, pages = {63-70}, pmid = {21109780}, issn = {1469-3178}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; Hypoxia-Inducible Factor 1/*physiology ; Molecular Sequence Data ; Oxygen/*physiology ; Phylogeny ; Placozoa/genetics/*physiology ; Procollagen-Proline Dioxygenase/physiology ; Transcriptional Activation ; Von Hippel-Lindau Tumor Suppressor Protein/physiology ; }, abstract = {The hypoxic response in humans is mediated by the hypoxia-inducible transcription factor (HIF), for which prolyl hydroxylases (PHDs) act as oxygen-sensing components. The evolutionary origins of the HIF system have been previously unclear. We demonstrate a functional HIF system in the simplest animal, Trichoplax adhaerens: HIF targets in T. adhaerens include glycolytic and metabolic enzymes, suggesting a role for HIF in the adaptation of basal multicellular animals to fluctuating oxygen levels. Characterization of the T. adhaerens PHDs and cross-species complementation assays reveal a conserved oxygen-sensing mechanism. Cross-genomic analyses rationalize the relative importance of HIF system components, and imply that the HIF system is likely to be present in all animals, but is unique to this kingdom.}, } @article {pmid21107374, year = {2010}, author = {Ehrlich, H and Deutzmann, R and Brunner, E and Cappellini, E and Koon, H and Solazzo, C and Yang, Y and Ashford, D and Thomas-Oates, J and Lubeck, M and Baessmann, C and Langrock, T and Hoffmann, R and Wörheide, G and Reitner, J and Simon, P and Tsurkan, M and Ereskovsky, AV and Kurek, D and Bazhenov, VV and Hunoldt, S and Mertig, M and Vyalikh, DV and Molodtsov, SL and Kummer, K and Worch, H and Smetacek, V and Collins, MJ}, title = {Mineralization of the metre-long biosilica structures of glass sponges is templated on hydroxylated collagen.}, journal = {Nature chemistry}, volume = {2}, number = {12}, pages = {1084-1088}, pmid = {21107374}, issn = {1755-4349}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Collagen/*chemistry ; Evolution, Molecular ; Hydroxylation ; Nanoparticles/chemistry/ultrastructure ; Porifera/*chemistry ; Silicon Dioxide/*chemistry ; }, abstract = {The minerals involved in the formation of metazoan skeletons principally comprise glassy silica, calcium phosphate or carbonate. Because of their ancient heritage, glass sponges (Hexactinellida) may shed light on fundamental questions such as molecular evolution, the unique chemistry and formation of the first skeletal silica-based structures, and the origin of multicellular animals. We have studied anchoring spicules from the metre-long stalk of the glass rope sponge (Hyalonema sieboldi; Porifera, Class Hexactinellida), which are remarkable for their size, durability, flexibility and optical properties. Using slow-alkali etching of biosilica, we isolated the organic fraction, which was revealed to be dominated by a hydroxylated fibrillar collagen that contains an unusual [Gly-3Hyp-4Hyp] motif. We speculate that this motif is predisposed for silica precipitation, and provides a novel template for biosilicification in nature.}, } @article {pmid21104016, year = {2011}, author = {Wang, A and Cao, ZY and Wang, P and Liu, AM and Pan, W and Wang, J and Zhu, GP}, title = {Heteroexpression and characterization of a monomeric isocitrate dehydrogenase from the multicellular prokaryote Streptomyces avermitilis MA-4680.}, journal = {Molecular biology reports}, volume = {38}, number = {6}, pages = {3717-3724}, pmid = {21104016}, issn = {1573-4978}, mesh = {Amino Acid Sequence ; Electrophoresis, Polyacrylamide Gel ; Enzyme Activation/drug effects ; *Gene Expression/drug effects ; Hydrogen-Ion Concentration/drug effects ; Indicators and Reagents/pharmacology ; Ions ; Isocitrate Dehydrogenase/chemistry/isolation & purification/*metabolism ; Kinetics ; Metals/pharmacology ; Molecular Sequence Data ; Molecular Weight ; Prokaryotic Cells/drug effects/*enzymology ; Recombinant Proteins/chemistry/metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; Streptomyces/drug effects/*enzymology ; Temperature ; }, abstract = {A monomeric NADP-dependent isocitrate dehydrogenase from the multicellular prokaryote Streptomyces avermitilis MA-4680 (SaIDH) was heteroexpressed in Escherichia coli, and the His-tagged enzyme was further purified to homogeneity. The molecular weight of SaIDH was about 80 kDa which is typical for monomeric isocitrate dehydrogenases. Structure-based sequence alignment reveals that the deduced amino acid sequence of SaIDH shows high sequence identity with known momomeric isocitrate dehydrogenase, and the coenzyme, substrate and metal ion binding sites are completely conserved. The optimal pH and temperature of SaIDH were found to be pH 9.4 and 45°C, respectively. Heat-inactivation studies showed that heating for 20 min at 50°C caused a 50% loss in enzymatic activity. In addition, SaIDH was absolutely specific for NADP+ as electron acceptor. Apparent Km values were 4.98 μM for NADP+ and 6,620 μM for NAD+, respectively, using Mn2+ as divalent cation. The enzyme performed a 33,000-fold greater specificity (kcat/Km) for NADP+ than NAD+. Moreover, SaIDH activity was entirely dependent on the presence of Mn2+ or Mg2+, but was strongly inhibited by Ca2+ and Zn2+. Taken together, our findings implicate the recombinant SaIDH is a divalent cation-dependent monomeric isocitrate dehydrogenase which presents a remarkably high cofactor preference for NADP+.}, } @article {pmid21098563, year = {2010}, author = {Juliano, CE and Swartz, SZ and Wessel, GM}, title = {A conserved germline multipotency program.}, journal = {Development (Cambridge, England)}, volume = {137}, number = {24}, pages = {4113-4126}, pmid = {21098563}, issn = {1477-9129}, support = {T32 GM007601/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Embryonic Development/genetics/physiology ; Gene Expression Regulation, Developmental/genetics/physiology ; Germ Cells/*cytology/metabolism ; Guanosine Monophosphate/metabolism ; Phylogeny ; Sea Urchins/embryology ; }, abstract = {The germline of multicellular animals is segregated from somatic tissues, which is an essential developmental process for the next generation. Although certain ecdysozoans and chordates segregate their germline during embryogenesis, animals from other taxa segregate their germline after embryogenesis from multipotent progenitor cells. An overlapping set of genes, including vasa, nanos and piwi, operate in both multipotent precursors and in the germline. As we propose here, this conservation implies the existence of an underlying germline multipotency program in these cell types that has a previously underappreciated and conserved function in maintaining multipotency.}, } @article {pmid21097929, year = {2010}, author = {Ronald, PC and Beutler, B}, title = {Plant and animal sensors of conserved microbial signatures.}, journal = {Science (New York, N.Y.)}, volume = {330}, number = {6007}, pages = {1061-1064}, doi = {10.1126/science.1189468}, pmid = {21097929}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Humans ; *Immunity/genetics ; Immunity, Innate ; Plant Proteins/genetics/immunology ; Plants/genetics/*immunology/microbiology ; *Receptors, Immunologic/physiology ; }, abstract = {The last common ancestor of plants and animals may have lived 1 billion years ago. Plants and animals have occasionally exchanged genes but, for the most part, have countered selective pressures independently. Microbes (bacteria, eukaryotes, and viruses) were omnipresent threats, influencing the direction of multicellular evolution. Receptors that detect molecular signatures of infectious organisms mediate awareness of nonself and are integral to host defense in plants and animals alike. The discoveries leading to elucidation of these receptors and their ligands followed a similar logical and methodological pathway in both plant and animal research.}, } @article {pmid21080937, year = {2010}, author = {Pollitt, LC and Colegrave, N and Khan, SM and Sajid, M and Reece, SE}, title = {Investigating the evolution of apoptosis in malaria parasites: the importance of ecology.}, journal = {Parasites & vectors}, volume = {3}, number = {}, pages = {105}, pmid = {21080937}, issn = {1756-3305}, abstract = {Apoptosis is a precisely regulated process of cell death which occurs widely in multicellular organisms and is essential for normal development and immune defences. In recent years, interest has grown in the occurrence of apoptosis in unicellular organisms. In particular, as apoptosis has been reported in a wide range of species, including protozoan malaria parasites and trypanosomes, it may provide a novel target for intervention. However, it is important to understand when and why parasites employ an apoptosis strategy before the likely long- and short-term success of such an intervention can be evaluated. The occurrence of apoptosis in unicellular parasites provides a challenge for evolutionary theory to explain as organisms are expected to have evolved to maximise their own proliferation, not death. One possible explanation is that protozoan parasites undergo apoptosis in order to gain a group benefit from controlling their density as this prevents premature vector mortality. However, experimental manipulations to examine the ultimate causes behind apoptosis in parasites are lacking. In this review, we focus on malaria parasites to outline how an evolutionary framework can help make predictions about the ecological circumstances under which apoptosis could evolve. We then highlight the ecological considerations that should be taken into account when designing evolutionary experiments involving markers of cell death, and we call for collaboration between researchers in different fields to identify and develop appropriate markers in reference to parasite ecology and to resolve debates on terminology.}, } @article {pmid21075744, year = {2011}, author = {Kim, TH and Kim, J and Heslop-Harrison, P and Cho, KH}, title = {Evolutionary design principles and functional characteristics based on kingdom-specific network motifs.}, journal = {Bioinformatics (Oxford, England)}, volume = {27}, number = {2}, pages = {245-251}, doi = {10.1093/bioinformatics/btq633}, pmid = {21075744}, issn = {1367-4811}, mesh = {Arabidopsis/metabolism ; *Biological Evolution ; *Feedback, Physiological ; Humans ; Models, Biological ; *Protein Interaction Mapping ; Saccharomyces cerevisiae/metabolism ; }, abstract = {BACKGROUND: Network motifs within biological networks show non-random abundances in systems at different scales. Large directed protein networks at the cellular level are now well defined in several diverse species. We aimed to compare the nature of significantly observed two- and three-node network motifs across three different kingdoms (Arabidopsis thaliana for multicellular plants, Saccharomyces cerevisiae for unicellular fungi and Homo sapiens for animals).

RESULTS: 'Two-node feedback' is the most significant motif in all three species. By considering the sign of each two-node feedback interaction, we examined the enrichment of the three types of two-node feedbacks [positive-positive (PP), negative-negative (NN) and positive-negative (PN)]. We found that PN is enriched in the network of A.thaliana, NN in the network of S.cerevisiae and PP and NN in the network of H.sapiens. Each feedback type has characteristic features of robustness, multistability and homeostasis.

CONCLUSIONS: We suggest that amplification of particular network motifs emerges from contrasting dynamical and topological properties of the motifs, reflects the evolutionary design principles selected by the characteristic behavior of each species and provides a signature pointing to their behavior and function.}, } @article {pmid21075047, year = {2010}, author = {Nishii, I and Miller, SM}, title = {Volvox: simple steps to developmental complexity?.}, journal = {Current opinion in plant biology}, volume = {13}, number = {6}, pages = {646-653}, doi = {10.1016/j.pbi.2010.10.005}, pmid = {21075047}, issn = {1879-0356}, mesh = {Biological Evolution ; Cell Division/genetics/physiology ; Chlamydomonas/*cytology/genetics/*growth & development ; Volvox/*cytology/genetics/*growth & development ; }, abstract = {Volvox, Chlamydomonas, and their close relatives - collectively the volvocine green algae - comprise an excellent system for investigating the origins of developmental complexity. Over a relatively short period of time Volvox evolved an impressive suite of developmental traits, including asymmetric cell division, multicellularity with germ-soma division of labor, embryonic morphogenesis, and oogamy. Recent molecular genetic analyses of important developmental genes and comparative analyses of the fully sequenced Volvox and Chlamydomonas genomes have provided important insights into how these and other traits came to be. Surprisingly, the acquisition of much of the developmental innovation in this family seems to have involved relatively minor tinkering with the ancestral unicellular blueprint.}, } @article {pmid21062861, year = {2010}, author = {Panagiotaki, N and Dajas-Bailador, F and Amaya, E and Papalopulu, N and Dorey, K}, title = {Characterisation of a new regulator of BDNF signalling, Sprouty3, involved in axonal morphogenesis in vivo.}, journal = {Development (Cambridge, England)}, volume = {137}, number = {23}, pages = {4005-4015}, pmid = {21062861}, issn = {1477-9129}, support = {/WT_/Wellcome Trust/United Kingdom ; 090868/WT_/Wellcome Trust/United Kingdom ; G0900584/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Axons/enzymology/*metabolism ; Base Sequence ; Brain-Derived Neurotrophic Factor/*metabolism ; Calcium Signaling ; Cerebral Cortex/cytology/metabolism ; Enzyme Activation ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression Regulation, Developmental ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mice ; Molecular Sequence Data ; *Morphogenesis/genetics ; Phylogeny ; Pseudopodia/metabolism ; Receptor, trkB/metabolism ; *Signal Transduction/genetics ; Spinal Cord/cytology/metabolism ; Time Factors ; Xenopus/embryology/genetics ; Xenopus Proteins/genetics/*metabolism ; }, abstract = {During development, many organs, including the kidney, lung and mammary gland, need to branch in a regulated manner to be functional. Multicellular branching involves changes in cell shape, proliferation and migration. Axonal branching, however, is a unicellular process that is mediated by changes in cell shape alone and as such appears very different to multicellular branching. Sprouty (Spry) family members are well-characterised negative regulators of Receptor tyrosine kinase (RTK) signalling. Knockout of Spry1, 2 and 4 in mouse result in branching defects in different organs, indicating an important role of RTK signalling in controlling branching pattern. We report here that Spry3, a previously uncharacterised member of the Spry family plays a role in axonal branching. We found that spry3 is expressed specifically in the trigeminal nerve and in spinal motor and sensory neurons in a Brain-derived neurotrophin factor (BDNF)-dependent manner. Knockdown of Spry3 expression causes an excess of axonal branching in spinal cord motoneurons in vivo. Furthermore, Spry3 inhibits the ability of BDNF to induce filopodia in Xenopus spinal cord neurons. Biochemically, we show that Spry3 represses calcium release downstream of BDNF signalling. Altogether, we have found that Spry3 plays an important role in the regulation of axonal branching of motoneurons in vivo, raising the possibility of unexpected conservation in the involvement of intracellular regulators of RTK signalling in multicellular and unicellular branching.}, } @article {pmid21057781, year = {2010}, author = {O'Connell, MJ}, title = {Selection and the cell cycle: positive Darwinian selection in a well-known DNA damage response pathway.}, journal = {Journal of molecular evolution}, volume = {71}, number = {5-6}, pages = {444-457}, pmid = {21057781}, issn = {1432-1432}, mesh = {Animals ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Cell Cycle/*genetics ; DNA Damage/*genetics ; Fanconi Anemia/genetics ; Haplotypes/genetics ; Humans ; Mice ; Models, Genetic ; Phylogeny ; *Selection, Genetic ; Signal Transduction/*genetics ; Software ; Species Specificity ; }, abstract = {Cancer is a common occurrence in multi-cellular organisms and is not strictly limited to the elderly in a population. It is therefore possible that individuals with genotypes that protect against early onset cancers have a selective advantage. In this study the patterns of mutation in the proteins of a well-studied DNA damage response pathway have been examined for evidence of adaptive evolutionary change. Using a maximum likelihood framework and the mammalian species phylogeny, together with codon models of evolution, selective pressure variation across the interacting network of proteins has been detected. The presence of signatures of adaptive evolution in BRCA1 and BRCA2 has already been documented but the effect on the entire network of interacting proteins in this damage response pathway has, until now, been unknown. Positive selection is evident throughout the network with a total of 11 proteins out of 15 examined displaying patterns of substitution characteristic of positive selection. It is also shown here that modern human populations display evidence of an ongoing selective sweep in 9 of these DNA damage repair proteins. The results presented here provide the community with new residues that may be relevant to cancer susceptibility while also highlighting those proteins where human and mouse have undergone lineage-specific functional shift. An understanding of this damage response pathway from an evolutionary perspective will undoubtedly contribute to future cancer treatment approaches.}, } @article {pmid21057645, year = {2010}, author = {Sebé-Pedrós, A and Ruiz-Trillo, I}, title = {Integrin-mediated adhesion complex: Cooption of signaling systems at the dawn of Metazoa.}, journal = {Communicative & integrative biology}, volume = {3}, number = {5}, pages = {475-477}, pmid = {21057645}, issn = {1942-0889}, abstract = {The integrin-mediated adhesion machinery is the primary cell-matrix adhesion mechanism in Metazoa. The integrin adhesion complex, which modulates important aspects of the cell physiology, is composed of integrins (alpha and beta subunits) and several scaffolding and signaling proteins. Integrins appeared to be absent in all non-metazoan eukaryotes so-far analyzed, including fungi, plants and choanoflagellates, the sister-group to Metazoa. Thus, integrins and, therefore, the integrin-mediated adhesion and signaling mechanism was considered a metazoan innovation. Recently, a broad comparative genomic analysis including new genome data from several unicellular organisms closely related to fungi and metazoans shattered previous views. The integrin adhesion and signaling complex is not specific to Metazoa, but rather it is present in apusozoans and holozoan protists. Thus, this important signaling and adhesion system predated the origin of Fungi and Metazoa, and was subsequently lost in fungi and choanoflagellates. This finding suggests that cooption played a more important role in the origin of Metazoa than previously believed. Here, we hypothesize that the integrin adhesome was ancestrally involved in signaling.}, } @article {pmid21051879, year = {2011}, author = {Loof, TG and Schmidt, O and Herwald, H and Theopold, U}, title = {Coagulation systems of invertebrates and vertebrates and their roles in innate immunity: the same side of two coins?.}, journal = {Journal of innate immunity}, volume = {3}, number = {1}, pages = {34-40}, doi = {10.1159/000321641}, pmid = {21051879}, issn = {1662-8128}, mesh = {Animals ; Biological Evolution ; Blood Coagulation/genetics/*immunology ; Blood Coagulation Factors/genetics/metabolism ; Humans ; Immunity, Innate/genetics/*immunology ; Insecta/genetics/immunology ; Invertebrates/genetics/*immunology ; Mammals/genetics/immunology ; Mice ; Vertebrates/genetics/*immunology ; }, abstract = {Bacterial infections represent a serious health care problem, and all multicellular organisms have developed defense mechanisms to eliminate pathogens that enter the host via different paths including wounds. Many invertebrates have an open circulatory system, and effective coagulation systems are in place to ensure fast and efficient closure of wounds. It was proposed early on that coagulation systems in invertebrates play a major role not only in sealing wounds but also in preventing systemic infections. More recent evidence suggests that vertebrates, too, rely on clotting as an immune effector mechanism. Here we discuss the evolution of clotting systems against the background of their versatile function in innate immunity.}, } @article {pmid21041555, year = {2011}, author = {DeBaryshe, PG and Pardue, ML}, title = {Differential maintenance of DNA sequences in telomeric and centromeric heterochromatin.}, journal = {Genetics}, volume = {187}, number = {1}, pages = {51-60}, pmid = {21041555}, issn = {1943-2631}, support = {R01 GM050315/GM/NIGMS NIH HHS/United States ; R56 GM050315/GM/NIGMS NIH HHS/United States ; GM50315/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Centromere/*genetics ; DNA/*genetics ; Drosophila melanogaster/cytology/*genetics ; Heterochromatin/*genetics/metabolism ; Retroelements/genetics ; Sequence Analysis, DNA ; Sequence Deletion ; Telomere/*genetics ; }, abstract = {Repeated DNA in heterochromatin presents enormous difficulties for whole-genome sequencing; hence, sequence organization in a significant portion of the genomes of multicellular organisms is relatively unknown. Two sequenced BACs now allow us to compare telomeric retrotransposon arrays from Drosophila melanogaster telomeres with an array of telomeric retrotransposons that transposed into the centromeric region of the Y chromosome >13 MYA, providing a unique opportunity to compare the structural evolution of this retrotransposon in two contexts. We find that these retrotransposon arrays, both heterochromatic, are maintained quite differently, resulting in sequence organizations that apparently reflect different roles in the two chromosomal environments. The telomere array has grown only by transposition of new elements to the chromosome end; the centromeric array instead has grown by repeated amplifications of segments of the original telomere array. Many elements in the telomere have been variably 5'-truncated apparently by gradual erosion and irregular deletions of the chromosome end; however, a significant fraction (4 and possibly 5 or 6 of 15 elements examined) remain complete and capable of further retrotransposition. In contrast, each element in the centromere region has lost ≥ 40% of its sequence by internal, rather than terminal, deletions, and no element retains a significant part of the original coding region. Thus the centromeric array has been restructured to resemble the highly repetitive satellite sequences typical of centromeres in multicellular organisms, whereas, over a similar or longer time period, the telomere array has maintained its ability to provide retrotransposons competent to extend telomere ends.}, } @article {pmid21036923, year = {2010}, author = {Denver, DR and Howe, DK and Wilhelm, LJ and Palmer, CA and Anderson, JL and Stein, KC and Phillips, PC and Estes, S}, title = {Selective sweeps and parallel mutation in the adaptive recovery from deleterious mutation in Caenorhabditis elegans.}, journal = {Genome research}, volume = {20}, number = {12}, pages = {1663-1671}, pmid = {21036923}, issn = {1549-5469}, mesh = {Adaptation, Biological/*genetics ; Animals ; Caenorhabditis elegans/*genetics ; Epistasis, Genetic/genetics ; *Evolution, Molecular ; Genetics, Population ; Mutation/*genetics ; *Selection, Genetic ; Sequence Analysis, DNA ; }, abstract = {Deleterious mutation poses a serious threat to human health and the persistence of small populations. Although adaptive recovery from deleterious mutation has been well-characterized in prokaryotes, the evolutionary mechanisms by which multicellular eukaryotes recover from deleterious mutation remain unknown. We applied high-throughput DNA sequencing to characterize genomic divergence patterns associated with the adaptive recovery from deleterious mutation using a Caenorhabditis elegans recovery-line system. The C. elegans recovery lines were initiated from a low-fitness mutation-accumulation (MA) line progenitor and allowed to independently evolve in large populations (N ∼ 1000) for 60 generations. All lines rapidly regained levels of fitness similar to the wild-type (N2) MA line progenitor. Although there was a near-zero probability of a single mutation fixing due to genetic drift during the recovery experiment, we observed 28 fixed mutations. Cross-generational analysis showed that all mutations went from undetectable population-level frequencies to a fixed state in 10-20 generations. Many recovery-line mutations fixed at identical timepoints, suggesting that the mutations, if not beneficial, hitchhiked to fixation during selective sweep events observed in the recovery lines. No MA line mutation reversions were detected. Parallel mutation fixation was observed for two sites in two independent recovery lines. Analysis using a C. elegans interactome map revealed many predicted interactions between genes with recovery line-specific mutations and genes with previously accumulated MA line mutations. Our study suggests that recovery-line mutations identified in both coding and noncoding genomic regions might have beneficial effects associated with compensatory epistatic interactions.}, } @article {pmid20976245, year = {2010}, author = {Bright, LJ and Kambesis, N and Nelson, SB and Jeong, B and Turkewitz, AP}, title = {Comprehensive analysis reveals dynamic and evolutionary plasticity of Rab GTPases and membrane traffic in Tetrahymena thermophila.}, journal = {PLoS genetics}, volume = {6}, number = {10}, pages = {e1001155}, pmid = {20976245}, issn = {1553-7404}, support = {R01 GM077607/GM/NIGMS NIH HHS/United States ; T32 GM007197/GM/NIGMS NIH HHS/United States ; GM077607/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Transport ; Blotting, Western ; Cell Membrane/*metabolism ; Endocytosis ; Eukaryotic Cells/metabolism ; Evolution, Molecular ; Genome, Protozoan ; Green Fluorescent Proteins/genetics/metabolism ; Microscopy, Fluorescence ; Multigene Family ; Phagocytosis ; Phylogeny ; Protozoan Proteins/*genetics/metabolism ; Signal Transduction ; Tetrahymena thermophila/*genetics/metabolism ; rab GTP-Binding Proteins/classification/*genetics/metabolism ; }, abstract = {Cellular sophistication is not exclusive to multicellular organisms, and unicellular eukaryotes can resemble differentiated animal cells in their complex network of membrane-bound structures. These comparisons can be illuminated by genome-wide surveys of key gene families. We report a systematic analysis of Rabs in a complex unicellular Ciliate, including gene prediction and phylogenetic clustering, expression profiling based on public data, and Green Fluorescent Protein (GFP) tagging. Rabs are monomeric GTPases that regulate membrane traffic. Because Rabs act as compartment-specific determinants, the number of Rabs in an organism reflects intracellular complexity. The Tetrahymena Rab family is similar in size to that in humans and includes both expansions in conserved Rab clades as well as many divergent Rabs. Importantly, more than 90% of Rabs are expressed concurrently in growing cells, while only a small subset appears specialized for other conditions. By localizing most Rabs in living cells, we could assign the majority to specific compartments. These results validated most phylogenetic assignments, but also indicated that some sequence-conserved Rabs were co-opted for novel functions. Our survey uncovered a rare example of a nuclear Rab and substantiated the existence of a previously unrecognized core Rab clade in eukaryotes. Strikingly, several functionally conserved pathways or structures were found to be associated entirely with divergent Rabs. These pathways may have permitted rapid evolution of the associated Rabs or may have arisen independently in diverse lineages and then converged. Thus, characterizing entire gene families can provide insight into the evolutionary flexibility of fundamental cellular pathways.}, } @article {pmid20971426, year = {2010}, author = {Fairclough, SR and Dayel, MJ and King, N}, title = {Multicellular development in a choanoflagellate.}, journal = {Current biology : CB}, volume = {20}, number = {20}, pages = {R875-6}, pmid = {20971426}, issn = {1879-0445}, support = {T32 HG000047/HG/NHGRI NIH HHS/United States ; R01 GM089977-02/GM/NIGMS NIH HHS/United States ; T32 HG 00047/HG/NHGRI NIH HHS/United States ; R01 GM089977/GM/NIGMS NIH HHS/United States ; GM089977/GM/NIGMS NIH HHS/United States ; }, mesh = {Aphidicolin/pharmacology ; *Biological Evolution ; Cell Division/drug effects/*physiology ; Cell Proliferation/drug effects ; Choanoflagellata/cytology/*growth & development ; Time-Lapse Imaging ; }, abstract = {Little is known about how the first animals evolved from their single celled ancestors. Over 120 years ago, Haeckel proposed that animals evolved through "repeated self-division of [a] primary cell,"[1] an idea supported by the observation that all animals develop from a single cell (the zygote) through successive rounds of cell division [2]. Nonetheless, there are multiple alternative hypotheses [3], including the formal possibility that multicellularity in the progenitor of animals occurred through cell aggregation, with embryogenesis by cell division being secondarily derived. The closest known relatives of animals, choanoflagellates, are emerging as a model system for testing specific hypotheses about animal origins [–7]. Studying colony formation in choanoflagellates may provide a context for reconstructing the evolution of animal multicellularity. We find that the transition from single cells to multicelled colonies in the choanoflagellate Salpingoeca rosetta occurs by cell division, with sister cells remaining stably attached.}, } @article {pmid20969480, year = {2011}, author = {Takeda, K and Naguro, I and Nishitoh, H and Matsuzawa, A and Ichijo, H}, title = {Apoptosis signaling kinases: from stress response to health outcomes.}, journal = {Antioxidants & redox signaling}, volume = {15}, number = {3}, pages = {719-761}, doi = {10.1089/ars.2010.3392}, pmid = {20969480}, issn = {1557-7716}, mesh = {Animals ; *Apoptosis ; Disease/genetics ; Humans ; Metabolic Networks and Pathways ; Mice ; Mice, Transgenic ; Phosphorylation ; Protein Kinases/classification/genetics/*metabolism ; *Stress, Physiological ; }, abstract = {Apoptosis is a highly regulated process essential for the development and homeostasis of multicellular organisms. Whereas caspases, a large family of intracellular cysteine proteases, play central roles in the execution of apoptosis, other proapoptotic and antiapoptotic regulators such as the members of the Bcl-2 family are also critically involved in the regulation of apoptosis. A large body of evidence has revealed that a number of protein kinases are among such regulators and regulate cellular sensitivity to various proapoptotic signals at multiple steps in apoptosis. However, recent progress in the analysis of these apoptosis signaling kinases demonstrates that they generally act as crucial regulators of diverse cellular responses to a wide variety of stressors, beyond their roles in apoptosis regulation. In this review, we have cataloged apoptosis signaling kinases involved in cellular stress responses on the basis of their ability to induce apoptosis and discuss their roles in stress responses with particular emphasis on health outcomes upon their dysregulation.}, } @article {pmid20962839, year = {2010}, author = {Lane, N and Martin, W}, title = {The energetics of genome complexity.}, journal = {Nature}, volume = {467}, number = {7318}, pages = {929-934}, pmid = {20962839}, issn = {1476-4687}, mesh = {Aerobiosis ; Anaerobiosis ; Animals ; Cell Nucleus/genetics ; Cell Size ; *Energy Metabolism ; Eukaryotic Cells/*cytology/*metabolism/ultrastructure ; Gene Expression ; Genes, Mitochondrial/genetics ; Genome/*genetics ; Humans ; Mitochondria/metabolism ; *Models, Biological ; Prokaryotic Cells/*cytology/*metabolism/ultrastructure ; Symbiosis/genetics/physiology ; }, abstract = {All complex life is composed of eukaryotic (nucleated) cells. The eukaryotic cell arose from prokaryotes just once in four billion years, and otherwise prokaryotes show no tendency to evolve greater complexity. Why not? Prokaryotic genome size is constrained by bioenergetics. The endosymbiosis that gave rise to mitochondria restructured the distribution of DNA in relation to bioenergetic membranes, permitting a remarkable 200,000-fold expansion in the number of genes expressed. This vast leap in genomic capacity was strictly dependent on mitochondrial power, and prerequisite to eukaryote complexity: the key innovation en route to multicellular life.}, } @article {pmid20959821, year = {2010}, author = {Boulais, J and Trost, M and Landry, CR and Dieckmann, R and Levy, ED and Soldati, T and Michnick, SW and Thibault, P and Desjardins, M}, title = {Molecular characterization of the evolution of phagosomes.}, journal = {Molecular systems biology}, volume = {6}, number = {}, pages = {423}, pmid = {20959821}, issn = {1744-4292}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; *Biological Evolution ; Cell Line ; Cluster Analysis ; Dictyostelium ; Drosophila ; Mice ; *Models, Biological ; Phagosomes/genetics/metabolism/*physiology ; Phosphoproteins/chemistry/metabolism/physiology ; Proteome/chemistry/metabolism/*physiology ; Proteomics/*methods ; Signal Transduction ; }, abstract = {Amoeba use phagocytosis to internalize bacteria as a source of nutrients, whereas multicellular organisms utilize this process as a defense mechanism to kill microbes and, in vertebrates, initiate a sustained immune response. By using a large-scale approach to identify and compare the proteome and phosphoproteome of phagosomes isolated from distant organisms, and by comparative analysis over 39 taxa, we identified an 'ancient' core of phagosomal proteins around which the immune functions of this organelle have likely organized. Our data indicate that a larger proportion of the phagosome proteome, compared with the whole cell proteome, has been acquired through gene duplication at a period coinciding with the emergence of innate and adaptive immunity. Our study also characterizes in detail the acquisition of novel proteins and the significant remodeling of the phagosome phosphoproteome that contributed to modify the core constituents of this organelle in evolution. Our work thus provides the first thorough analysis of the changes that enabled the transformation of the phagosome from a phagotrophic compartment into an organelle fully competent for antigen presentation.}, } @article {pmid20936119, year = {2010}, author = {Eoff, RL and Choi, JY and Guengerich, FP}, title = {Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage.}, journal = {Journal of nucleic acids}, volume = {2010}, number = {}, pages = {}, pmid = {20936119}, issn = {2090-021X}, support = {K99 GM084460/GM/NIGMS NIH HHS/United States ; P30 ES000267/ES/NIEHS NIH HHS/United States ; R01 ES010375/ES/NIEHS NIH HHS/United States ; R01 ES010546/ES/NIEHS NIH HHS/United States ; }, abstract = {DNA is a chemically reactive molecule that is subject to many different covalent modifications from sources that are both endogenous and exogenous in origin. The inherent instability of DNA is a major obstacle to genomic maintenance and contributes in varying degrees to cellular dysfunction and disease in multi-cellular organisms. Investigations into the chemical and biological aspects of DNA damage have identified multi-tiered and overlapping cellular systems that have evolved as a means of stabilizing the genome. One of these pathways supports DNA replication events by in a sense adopting the mantra that one must "make the best of a bad situation" and tolerating covalent modification to DNA through less accurate copying of the damaged region. Part of this so-called DNA damage tolerance pathway involves the recruitment of specialized DNA polymerases to sites of stalled or collapsed replication forks. These enzymes have unique structural and functional attributes that often allow bypass of adducted template DNA and successful completion of genomic replication. What follows is a selective description of the salient structural features and bypass properties of specialized DNA polymerases with an emphasis on Y-family members.}, } @article {pmid20935258, year = {2010}, author = {Charoensawan, V and Adryan, B and Martin, S and Söllner, C and Thisse, B and Thisse, C and Wright, GJ and Teichmann, SA}, title = {The impact of gene expression regulation on evolution of extracellular signaling pathways.}, journal = {Molecular & cellular proteomics : MCP}, volume = {9}, number = {12}, pages = {2666-2677}, pmid = {20935258}, issn = {1535-9484}, support = {MC_U105161047/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Evolution, Molecular ; *Gene Expression Regulation ; In Situ Hybridization ; *Signal Transduction ; Zebrafish ; Zebrafish Proteins/*genetics/metabolism ; }, abstract = {Extracellular protein interactions are crucial to the development of multicellular organisms because they initiate signaling pathways and enable cellular recognition cues. Despite their importance, extracellular protein interactions are often under-represented in large scale protein interaction data sets because most high throughput assays are not designed to detect low affinity extracellular interactions. Due to the lack of a comprehensive data set, the evolution of extracellular signaling pathways has remained largely a mystery. We investigated this question using a combined data set of physical pairwise interactions between zebrafish extracellular proteins, mainly from the immunoglobulin superfamily and leucine-rich repeat families, and their spatiotemporal expression profiles. We took advantage of known homology between proteins to estimate the relative rates of changes of four parameters after gene duplication, namely extracellular protein interaction, expression pattern, and the divergence of extracellular and intracellular protein sequences. We showed that change in expression profile is a major contributor to the evolution of signaling pathways followed by divergence in intracellular protein sequence, whereas extracellular sequence and interaction profiles were relatively more conserved. Rapidly evolving expression profiles will eventually drive other parameters to diverge more quickly because differentially expressed proteins get exposed to different environments and potential binding partners. This allows homologous extracellular receptors to attain specialized functions and become specific to tissues and/or developmental stages.}, } @article {pmid20924085, year = {2011}, author = {Montanucci, L and Laayouni, H and Dall'Olio, GM and Bertranpetit, J}, title = {Molecular evolution and network-level analysis of the N-glycosylation metabolic pathway across primates.}, journal = {Molecular biology and evolution}, volume = {28}, number = {1}, pages = {813-823}, doi = {10.1093/molbev/msq259}, pmid = {20924085}, issn = {1537-1719}, mesh = {Adaptation, Physiological/genetics ; Animals ; Base Sequence ; *Evolution, Molecular ; Glycosylation ; Metabolic Networks and Pathways/*genetics ; Molecular Sequence Data ; Multivariate Analysis ; Polysaccharides/chemistry/metabolism ; Primates/*genetics/*metabolism ; Selection, Genetic/*genetics ; Sequence Alignment ; }, abstract = {N-glycosylation is one of the most important forms of protein modification, serving key biological functions in multicellular organisms. N-glycans at the cell surface mediate the interaction between cells and the surrounding matrix and may act as pathogen receptors, making the genes responsible for their synthesis good candidates to show signatures of adaptation to different pathogen environments. Here, we study the forces that shaped the evolution of the genes involved in the synthesis of the N-glycans during the divergence of primates within the framework of their functional network. We have found that, despite their function of producing glycan repertoires capable of evading rapidly evolving pathogens, genes involved in the synthesis of the glycans are highly conserved, and no signals of positive selection have been detected within the time of divergence of primates. This suggests strong functional constraints as the main force driving their evolution. We studied the strength of the purifying selection acting on the genes in relation to the network structure considering the position of each gene along the pathway, its connectivity, and the rates of evolution in neighboring genes. We found a strong and highly significant negative correlation between the strength of purifying selection and the connectivity of each gene, indicating that genes encoding for highly connected enzymes evolve slower and thus are subject to stronger selective constraints. This result confirms that network topology does shape the evolution of the genes and that the connectivity within metabolic pathways and networks plays a major role in constraining evolutionary rates.}, } @article {pmid20920349, year = {2010}, author = {Pang, K and Ryan, JF and , and Mullikin, JC and Baxevanis, AD and Martindale, MQ}, title = {Genomic insights into Wnt signaling in an early diverging metazoan, the ctenophore Mnemiopsis leidyi.}, journal = {EvoDevo}, volume = {1}, number = {1}, pages = {10}, pmid = {20920349}, issn = {2041-9139}, abstract = {BACKGROUND: Intercellular signaling pathways are a fundamental component of the integrating cellular behavior required for the evolution of multicellularity. The genomes of three of the four early branching animal phyla (Cnidaria, Placozoa and Porifera) have been surveyed for key components, but not the fourth (Ctenophora). Genomic data from ctenophores could be particularly relevant, as ctenophores have been proposed to be one of the earliest branching metazoan phyla.

RESULTS: A preliminary assembly of the lobate ctenophore Mnemiopsis leidyi genome generated using next-generation sequencing technologies were searched for components of a developmentally important signaling pathway, the Wnt/β-catenin pathway. Molecular phylogenetic analysis shows four distinct Wnt ligands (MlWnt6, MlWnt9, MlWntA and MlWntX), and most, but not all components of the receptor and intracellular signaling pathway were detected. In situ hybridization of the four Wnt ligands showed that they are expressed in discrete regions associated with the aboral pole, tentacle apparati and apical organ.

CONCLUSIONS: Ctenophores show a minimal (but not obviously simple) complement of Wnt signaling components. Furthermore, it is difficult to compare the Mnemiopsis Wnt expression patterns with those of other metazoans. mRNA expression of Wnt pathway components appears later in development than expected, and zygotic gene expression does not appear to play a role in early axis specification. Notably absent in the Mnemiopsis genome are most major secreted antagonists, which suggests that complex regulation of this secreted signaling pathway probably evolved later in animal evolution.}, } @article {pmid20889898, year = {2010}, author = {Norton, AJ and Gower, CM and Lamberton, PH and Webster, BL and Lwambo, NJ and Blair, L and Fenwick, A and Webster, JP}, title = {Genetic consequences of mass human chemotherapy for Schistosoma mansoni: population structure pre- and post-praziquantel treatment in Tanzania.}, journal = {The American journal of tropical medicine and hygiene}, volume = {83}, number = {4}, pages = {951-957}, pmid = {20889898}, issn = {1476-1645}, support = {/WT_/Wellcome Trust/United Kingdom ; WT063774/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Child ; Cluster Analysis ; Genetic Variation ; Humans ; Phylogeny ; Praziquantel/administration & dosage/*therapeutic use ; Schistosoma mansoni/drug effects/*genetics ; Schistosomiasis mansoni/*drug therapy/epidemiology ; Schistosomicides/administration & dosage/*therapeutic use ; Tanzania/epidemiology ; Time Factors ; }, abstract = {Recent shifts in global health policy have led to the implementation of mass drug administration (MDA) for neglected tropical diseases. Here we show how population genetic analyses can provide vital insights into the impact of such MDA on endemic parasite populations. We show that even a single round of MDA produced a genetic bottleneck with reductions in a range of measures of genetic diversity of Schistosoma mansoni. Phylogenetic analyses and indices of population differentiation indicated that schistosomes collected in the same schools in different years were more dissimilar than those from different schools collected within either of the study's 2 years, in addition to distinguishing re-infection from non-clearance (that might indicate putatively resistant parasites) from within those children infected at both baseline and follow-up. Such unique results illustrate the importance of genetic monitoring and examination of long lived multi-cellular parasites such as these under novel or increased chemotherapeutic selective pressures.}, } @article {pmid20888233, year = {2011}, author = {Jedd, G}, title = {Fungal evo-devo: organelles and multicellular complexity.}, journal = {Trends in cell biology}, volume = {21}, number = {1}, pages = {12-19}, doi = {10.1016/j.tcb.2010.09.001}, pmid = {20888233}, issn = {1879-3088}, mesh = {Ascomycota/cytology/genetics ; Basidiomycota/cytology/genetics ; Cytoplasm/metabolism ; Fungi/*cytology/*genetics/metabolism ; Organelles/*genetics/metabolism ; }, abstract = {Peroxisome-derived Woronin bodies of the Ascomycota phyla, and the endoplasmic reticulum (ER)-derived septal pore cap (SPC) of the Basidiomycota, are both fungal organelles that prevent cytoplasmic bleeding when multicellular hyphal filaments are wounded. Analysis of Woronin body constituent proteins suggests that these organelles evolved in part through gene duplication and co-opting of non-essential genes for new functions, indicating that new organelles can arise through typical evolutionary mechanisms. Interestingly, clades possessing the Woronin body and SPC also produce the largest and most complex multicellular fungal reproductive structures. Certain Woronin body and SPC mutants have defects in growth and development, suggesting functions beyond cellular wound healing. I argue that studying these specialized systems will help to reveal the basis for fungal diversity and provide general principles for co-evolution of organelles and multicellular complexity.}, } @article {pmid20885784, year = {2010}, author = {Burns, C and Stajich, JE and Rechtsteiner, A and Casselton, L and Hanlon, SE and Wilke, SK and Savytskyy, OP and Gathman, AC and Lilly, WW and Lieb, JD and Zolan, ME and Pukkila, PJ}, title = {Analysis of the Basidiomycete Coprinopsis cinerea reveals conservation of the core meiotic expression program over half a billion years of evolution.}, journal = {PLoS genetics}, volume = {6}, number = {9}, pages = {e1001135}, pmid = {20885784}, issn = {1553-7404}, support = {R01 GM043930/GM/NIGMS NIH HHS/United States ; GM43930/GM/NIGMS NIH HHS/United States ; }, mesh = {Basidiomycota/*cytology/*genetics ; Cell Nucleus/genetics ; Cluster Analysis ; Conserved Sequence/*genetics ; *Evolution, Molecular ; Fungal Proteins/genetics/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Fungal ; Genes, Fungal/*genetics ; History, Ancient ; Meiosis/*genetics ; Multigene Family/genetics ; Saccharomyces cerevisiae/genetics ; Schizosaccharomyces/genetics ; Time Factors ; Transcription, Genetic ; }, abstract = {Coprinopsis cinerea (also known as Coprinus cinereus) is a multicellular basidiomycete mushroom particularly suited to the study of meiosis due to its synchronous meiotic development and prolonged prophase. We examined the 15-hour meiotic transcriptional program of C. cinerea, encompassing time points prior to haploid nuclear fusion though tetrad formation, using a 70-mer oligonucleotide microarray. As with other organisms, a large proportion (∼20%) of genes are differentially regulated during this developmental process, with successive waves of transcription apparent in nine transcriptional clusters, including one enriched for meiotic functions. C. cinerea and the fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe diverged ∼500-900 million years ago, permitting a comparison of transcriptional programs across a broad evolutionary time scale. Previous studies of S. cerevisiae and S. pombe compared genes that were induced upon entry into meiosis; inclusion of C. cinerea data indicates that meiotic genes are more conserved in their patterns of induction across species than genes not known to be meiotic. In addition, we found that meiotic genes are significantly more conserved in their transcript profiles than genes not known to be meiotic, which indicates a remarkable conservation of the meiotic process across evolutionarily distant organisms. Overall, meiotic function genes are more conserved in both induction and transcript profile than genes not known to be meiotic. However, of 50 meiotic function genes that were co-induced in all three species, 41 transcript profiles were well-correlated in at least two of the three species, but only a single gene (rad50) exhibited coordinated induction and well-correlated transcript profiles in all three species, indicating that co-induction does not necessarily predict correlated expression or vice versa. Differences may reflect differences in meiotic mechanisms or new roles for paralogs. Similarities in induction, transcript profiles, or both, should contribute to gene discovery for orthologs without currently characterized meiotic roles.}, } @article {pmid20883217, year = {2010}, author = {Windsor, PJ and Leys, SP}, title = {Wnt signaling and induction in the sponge aquiferous system: evidence for an ancient origin of the organizer.}, journal = {Evolution & development}, volume = {12}, number = {5}, pages = {484-493}, doi = {10.1111/j.1525-142X.2010.00434.x}, pmid = {20883217}, issn = {1525-142X}, mesh = {Animals ; Benzazepines/pharmacology ; Body Patterning ; Indoles/pharmacology ; Lithium Chloride/pharmacology ; Porifera/drug effects/growth & development/*metabolism ; *Signal Transduction ; Wnt Proteins/metabolism/*physiology ; }, abstract = {The importance of polarity-the possession of a primary body axis-is evident in the functional features of animals, such as feeding, and therefore must have arisen simultaneously with the evolution of multicellular animal body plans. Sponges are thought to represent the most ancient extant lineage of multicellular animals and whereas adult sponges do not possess obvious polarity, they are useful study organisms in which to examine the origin and evolution of body polarity. We tested the effect of pharmacological agents known to disrupt the polarity of a wide variety of animals on sponge organization during development. Lithium chloride and alsterpaullone, which mimic canonical Wnt signaling in other animals, caused formation of ectopic oscula and disrupted the ability of the sponge to feed. Transplanted oscula were able to attach to and induce canal reorganization in host sponges suggesting that the osulum has inductive capabilities. This work suggests that canonical Wnt signaling is responsible for setting up the aquiferous system, which acts as an organizing center polarizing the sponge.}, } @article {pmid20868222, year = {2010}, author = {Dieckmann, M and Dietrich, MF and Herz, J}, title = {Lipoprotein receptors--an evolutionarily ancient multifunctional receptor family.}, journal = {Biological chemistry}, volume = {391}, number = {11}, pages = {1341-1363}, pmid = {20868222}, issn = {1437-4315}, support = {P01 HL020948/HL/NHLBI NIH HHS/United States ; R01 HL063762/HL/NHLBI NIH HHS/United States ; R37 HL063762/HL/NHLBI NIH HHS/United States ; }, mesh = {Alzheimer Disease/etiology/genetics/metabolism ; Amyloid beta-Protein Precursor/genetics/metabolism ; Animals ; Atherosclerosis/etiology/genetics/metabolism ; Carrier Proteins/genetics/metabolism ; Cell Membrane/genetics/metabolism ; *Evolution, Molecular ; Humans ; Lipoproteins/genetics/metabolism ; *Lipoproteins, LDL/genetics/metabolism ; Mice ; Neuromuscular Junction/metabolism ; Protein Binding ; *Receptors, LDL/genetics/metabolism ; *Receptors, Lipoprotein/genetics/metabolism ; Signal Transduction/physiology ; }, abstract = {The evolutionarily ancient low-density lipoprotein (LDL) receptor gene family represents a class of widely expressed cell surface receptors. Since the dawn of the first primitive multicellular organisms, several structurally and functionally distinct families of lipoprotein receptors have evolved. In accordance with the now obsolete 'one-gene-one-function' hypothesis, these cell surface receptors were originally perceived as mere transporters of lipoproteins, lipids, and nutrients or as scavenger receptors, which remove other kinds of macromolecules, such as proteases and protease inhibitors from the extracellular environment and the cell surface. This picture has since undergone a fundamental change. Experimental evidence has replaced the perception that these receptors serve merely as cargo transporters. Instead it is now clear that the transport of macromolecules is inseparably intertwined with the molecular machinery by which cells communicate with each other. Lipoprotein receptors are essentially sensors of the extracellular environment that participate in a wide range of physiological processes by physically interacting and coevolving with primary signal transducers as co-regulators. Furthermore, lipoprotein receptors modulate cellular trafficking and localization of the amyloid precursor protein (APP) and the β-amyloid peptide (Aβ), suggesting a role in the pathogenesis of Alzheimer's disease. Moreover, compelling evidence shows that LDL receptor family members are involved in tumor development and progression.}, } @article {pmid20863387, year = {2010}, author = {Shertz, CA and Bastidas, RJ and Li, W and Heitman, J and Cardenas, ME}, title = {Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom.}, journal = {BMC genomics}, volume = {11}, number = {}, pages = {510}, pmid = {20863387}, issn = {1471-2164}, support = {R01 AI050438/AI/NIAID NIH HHS/United States ; R01 CA154499/CA/NCI NIH HHS/United States ; AI050438-08/AI/NIAID NIH HHS/United States ; CA114107/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Conserved Sequence/*genetics ; Evolution, Molecular ; Fungal Proteins/chemistry/genetics/*metabolism ; Fungi/*enzymology/*genetics ; Gene Duplication/*genetics ; Genome, Fungal/genetics ; Microsporidia/enzymology/genetics ; Molecular Sequence Data ; Phylogeny ; Saccharomyces cerevisiae/enzymology/genetics ; Schizosaccharomyces/enzymology/genetics ; Signal Transduction/*genetics ; Synteny ; }, abstract = {BACKGROUND: The nutrient-sensing Tor pathway governs cell growth and is conserved in nearly all eukaryotic organisms from unicellular yeasts to multicellular organisms, including humans. Tor is the target of the immunosuppressive drug rapamycin, which in complex with the prolyl isomerase FKBP12 inhibits Tor functions. Rapamycin is a gold standard drug for organ transplant recipients that was approved by the FDA in 1999 and is finding additional clinical indications as a chemotherapeutic and antiproliferative agent. Capitalizing on the plethora of recently sequenced genomes we have conducted comparative genomic studies to annotate the Tor pathway throughout the fungal kingdom and related unicellular opisthokonts, including Monosiga brevicollis, Salpingoeca rosetta, and Capsaspora owczarzaki.

RESULTS: Interestingly, the Tor signaling cascade is absent in three microsporidian species with available genome sequences, the only known instance of a eukaryotic group lacking this conserved pathway. The microsporidia are obligate intracellular pathogens with highly reduced genomes, and we hypothesize that they lost the Tor pathway as they adapted and streamlined their genomes for intracellular growth in a nutrient-rich environment. Two TOR paralogs are present in several fungal species as a result of either a whole genome duplication or independent gene/segmental duplication events. One such event was identified in the amphibian pathogen Batrachochytrium dendrobatidis, a chytrid responsible for worldwide global amphibian declines and extinctions.

CONCLUSIONS: The repeated independent duplications of the TOR gene in the fungal kingdom might reflect selective pressure acting upon this kinase that populates two proteinaceous complexes with different cellular roles. These comparative genomic analyses illustrate the evolutionary trajectory of a central nutrient-sensing cascade that enables diverse eukaryotic organisms to respond to their natural environments.}, } @article {pmid20862689, year = {2010}, author = {Kandasamy, MK and McKinney, EC and Meagher, RB}, title = {Differential sublocalization of actin variants within the nucleus.}, journal = {Cytoskeleton (Hoboken, N.J.)}, volume = {67}, number = {11}, pages = {729-743}, pmid = {20862689}, issn = {1949-3592}, support = {R01 GM036397/GM/NIGMS NIH HHS/United States ; GM36397/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/classification/genetics/*metabolism ; Amino Acid Sequence ; Animals ; Arabidopsis/cytology/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Cell Nucleus/*metabolism ; Destrin/metabolism ; Gene Expression Regulation, Plant ; Molecular Sequence Data ; Nuclear Localization Signals ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Profilins/metabolism ; Protein Isoforms/classification/genetics/*metabolism ; }, abstract = {Conventional actin has been implicated in various nuclear processes including chromatin remodeling, transcription, nuclear transport, and overall nuclear structure. Moreover, actin has been identified as a component of several chromatin remodeling complexes present in the nucleus. In animal cells, nuclear actin exists as a dynamic equilibrium of monomers and polymers. Actin-binding proteins (ABPs) such as ADF/cofilin and profilin play a role in actin import and export, respectively. However, very little is known about the localization and roles of nuclear actin in plants. In multicellular plants and animals, actin is comprised of an ancient and divergent family of protein variants. Here, we have investigated the presence and differential localization of two ancient subclasses of actin in isolated Arabidopsis nuclei. Although the subclass 1 variants ACT2 and ACT8 and subclass 2 variant ACT7 were found distributed throughout the nucleoplasm, ACT7 was often found more concentrated in nuclear speckles than subclass 1 variants. The nuclei from the act2-1/act8-2 double null mutant and the act7-5 null mutant lacked their corresponding actin variants. In addition, serial sectioning of several independent nuclei revealed that ACT7 was notably more abundant in the nucleolus than the subclass 1 actins. Profilin and ADF proteins were also found in significant levels in plant nuclei. The possible functions of differentially localized nuclear actin variants are discussed.}, } @article {pmid20862320, year = {2010}, author = {Gutiérrez, S and Yvon, M and Thébaud, G and Monsion, B and Michalakis, Y and Blanc, S}, title = {Dynamics of the multiplicity of cellular infection in a plant virus.}, journal = {PLoS pathogens}, volume = {6}, number = {9}, pages = {e1001113}, pmid = {20862320}, issn = {1553-7374}, mesh = {Brassica napus/genetics/*virology ; Caulimovirus/classification/*pathogenicity ; Genetic Complementation Test ; Plant Diseases/genetics/*virology ; Plant Leaves/genetics/*virology ; Recombination, Genetic ; }, abstract = {Recombination, complementation and competition profoundly influence virus evolution and epidemiology. Since viruses are intracellular parasites, the basic parameter determining the potential for such interactions is the multiplicity of cellular infection (cellular MOI), i.e. the number of viral genome units that effectively infect a cell. The cellular MOI values that prevail in host organisms have rarely been investigated, and whether they remain constant or change widely during host invasion is totally unknown. Here, we fill this experimental gap by presenting the first detailed analysis of the dynamics of the cellular MOI during colonization of a host plant by a virus. Our results reveal ample variations between different leaf levels during the course of infection, with values starting close to 2 and increasing up to 13 before decreasing to initial levels in the latest infection stages. By revealing wide dynamic changes throughout a single infection, we here illustrate the existence of complex scenarios where the opportunity for recombination, complementation and competition among viral genomes changes greatly at different infection phases and at different locations within a multi-cellular host.}, } @article {pmid20861881, year = {2010}, author = {Méchali, M}, title = {Eukaryotic DNA replication origins: many choices for appropriate answers.}, journal = {Nature reviews. Molecular cell biology}, volume = {11}, number = {10}, pages = {728-738}, pmid = {20861881}, issn = {1471-0080}, mesh = {Animals ; Cell Division/genetics ; DNA Damage ; *DNA Replication ; Drosophila/genetics ; Eukaryotic Cells/*physiology ; Genome ; Replication Origin/*genetics ; Transcription, Genetic ; Xenopus/genetics ; }, abstract = {At each cell division in humans, 30,000-50,000 DNA replication origins are activated, and it remains unclear how they are selected and recognized by replication factors. DNA replication in multicellular organisms must accommodate variations in growth conditions and DNA damage. It must also adapt to changes in chromatin organization associated with cell differentiation and development. The selection of replication origins in metazoans seems to involve multiple choices, with the appropriate answers depending on the identity of the cell or the conditions of growth. This suggests that during evolution, the use of replication origins became more controlled by epigenetic mechanisms affecting chromosome dynamics and expression than by DNA synthesis per se.}, } @article {pmid20857205, year = {2011}, author = {Wang, L and Liu, Y and Wang, WN and Mai, WJ and Xin, Y and Zhou, J and He, WY and Wang, AL and Sun, RY}, title = {Molecular characterization and expression analysis of elongation factors 1A and 2 from the Pacific white shrimp, Litopenaeus vannamei.}, journal = {Molecular biology reports}, volume = {38}, number = {3}, pages = {2167-2178}, pmid = {20857205}, issn = {1573-4978}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Cadmium/toxicity ; Cloning, Molecular ; *Gene Expression Profiling ; Gene Expression Regulation ; Hepatopancreas/drug effects/metabolism ; Humans ; Hydrogen-Ion Concentration/drug effects ; Molecular Sequence Data ; Pacific Ocean ; Penaeidae/drug effects/*genetics ; Peptide Elongation Factor 1/chemistry/*genetics/metabolism ; Peptide Elongation Factor 2/chemistry/*genetics/metabolism ; Phylogeny ; Sequence Alignment ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Elongation factors (EF) are abundant cell proteins that play important roles in the metabolism of all multicellular organisms. Here we describe a functional analysis of elongation factor 1-alpha (EF1A) and elongation factor 2 (EF2), from the Pacific white shrimp, Litopenaeus vannamei. Full-length cDNAs of genes corresponding to EF1A and EF2 were obtained that were 1547 and 2729 bp long, with open reading frames encoding 461 and 846 amino acids, respectively. The deduced amino acid sequences of L. vannamei EF1A and EF2 showed high similarity with those from mice, humans, chickens and other shrimps. RT-PCR analysis indicated that mRNA transcripts of EF1A and EF2 are strongly (but differentially) expressed in haemocytes and gill tissue, and at varying levels in other examined tissues, of the shrimps. Levels of both EF1A and EF2 transcripts increased when shrimps were challenged by pH and cadmium stress, but reached maximal levels after different exposure periods. These results indicate that EF1A and EF2 may play distinct, essential roles in the repair of cellular damage induced by pH and cadmium stress.}, } @article {pmid20849664, year = {2010}, author = {Cao, L and Peng, B and Yao, L and Zhang, X and Sun, K and Yang, X and Yu, L}, title = {The ancient function of RB-E2F pathway: insights from its evolutionary history.}, journal = {Biology direct}, volume = {5}, number = {}, pages = {55}, pmid = {20849664}, issn = {1745-6150}, mesh = {Animals ; E2F Transcription Factors/classification/genetics/*metabolism ; Evolution, Molecular ; Humans ; Phylogeny ; Retinoblastoma Protein/classification/genetics/*metabolism ; Signal Transduction/genetics/*physiology ; }, abstract = {BACKGROUND: The RB-E2F pathway is conserved in most eukaryotic lineages, including animals and plants. E2F and RB family proteins perform crucial functions in cycle controlling, differentiation, development and apoptosis. However, there are two kinds of E2Fs (repressive E2Fs and active E2Fs) and three RB family members in human. Till now, the detail evolutionary history of these protein families and how RB-E2F pathway evolved in different organisms remain poorly explored.

RESULTS: We performed a comprehensive evolutionary analysis of E2F, RB and DP (dimerization partners of E2Fs) protein family in representative eukaryotic organisms. Several interesting facts were revealed. First, orthologues of RB, E2F, and DP family are present in several representative unicellular organisms and all multicellular organisms we checked. Second, ancestral E2F, RB genes duplicated before placozoans and bilaterians diverged, thus E2F family was divided into E2F4/5 subgroup (including repressive E2Fs: E2F4 and E2F5) and E2F1/2/3 subgroup (including active E2Fs: E2F1, E2F2 and E2F3), RB family was divided into RB1 subgroup (including RB1) and RBL subgroup (including RBL1 and RBL2). Third, E2F4 and E2F5 share more sequence similarity with the predicted E2F ancestral sequence than E2F1, E2F2 and E2F3; E2F4 and E2F5 also possess lower evolutionary rates and higher purification selection pressures than E2F1, E2F2 and E2F3. Fourth, for RB family, the RBL subgroup proteins possess lower evolutionary rates and higher purification selection pressures compared with RB subgroup proteins in vertebrates,

CONCLUSIONS: Protein evolutionary rates and purification selection pressures are usually linked with protein functions. We speculated that function conducted by E2F4/5 subgroup and RBL subgroup proteins might mainly represent the ancient function of RB-E2F pathway, and the E2F1/2/3 subgroup proteins and RB1 protein might contribute more to functional diversification in RB-E2F pathway. Our results will enhance the current understanding of RB-E2F pathway and will also be useful to further functional studies in human and other model organisms.}, } @article {pmid20845078, year = {2011}, author = {Wang, ZD and Wang, BJ and Ge, YD and Pan, W and Wang, J and Xu, L and Liu, AM and Zhu, GP}, title = {Expression and identification of a thermostable malate dehydrogenase from multicellular prokaryote Streptomyces avermitilis MA-4680.}, journal = {Molecular biology reports}, volume = {38}, number = {3}, pages = {1629-1636}, pmid = {20845078}, issn = {1573-4978}, mesh = {Amino Acid Sequence ; Biocatalysis/drug effects ; Blotting, Western ; Electrophoresis, Polyacrylamide Gel ; Enzyme Activation/drug effects ; Enzyme Stability/drug effects ; Hydrogen-Ion Concentration/drug effects ; Ions ; Kinetics ; Malate Dehydrogenase/chemistry/isolation & purification/*metabolism ; Malates/pharmacology ; Metals/pharmacology ; Molecular Sequence Data ; Oxaloacetic Acid/metabolism ; Prokaryotic Cells/*cytology/drug effects/*enzymology ; Recombinant Proteins/metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; Streptomyces/*cytology/drug effects/*enzymology ; Temperature ; }, abstract = {A malate dehydrogenase (MDH) from Streptomyces avermitilis MA-4680 (SaMDH) has been expressed and purified as a fusion protein. The molecular mass of SaMDH is about 35 kDa determined by SDS-PAGE. The recombinant SaMDH has a maximum activity at pH 8.0. The enzyme shows the optimal temperature around 42 °C and displays a half-life (t(1/2)) of 160 min at 50°C which is more thermostable than reported MDHs from most bacteria and fungi. The k(cat) value of SaMDH is about 240-fold of that for malate oxidation. In addition, the k(cat)/K(m) ratio shows that SaMDH has about 1,246-fold preference for oxaloacetate (OAA) reduction over L-malate oxidation. The recombinant SaMDH may also use NADPH as a cofactor although it is a highly NAD(H)-specific enzyme. There was no activity detected when malate and NADP(+) were used as substrates. Substrate inhibition studies show that SaMDH activity is strongly inhibited by excess OAA with NADH, but is not sensitive to excess L-malate. Enzymatic activity is enhanced by the addition of Na(+), NH(4)(+), Ca(2+), Cu(2+) and Mg(2+) and inhibited by addition of Hg(2+) and Zn(2+). MDH is widely used in coenzyme regeneration, antigen immunoassays and bioreactors. The enzymatic analysis could provide the important basic knowledge for its utilizations.}, } @article {pmid20837096, year = {2010}, author = {Lobo, D and Vico, FJ}, title = {Evolution of form and function in a model of differentiated multicellular organisms with gene regulatory networks.}, journal = {Bio Systems}, volume = {102}, number = {2-3}, pages = {112-123}, doi = {10.1016/j.biosystems.2010.08.003}, pmid = {20837096}, issn = {1872-8324}, mesh = {Adaptation, Physiological/*genetics ; Algorithms ; Animals ; *Evolution, Molecular ; Gene Expression Profiling ; *Gene Regulatory Networks ; Genetic Variation ; Humans ; *Models, Genetic ; Polymorphism, Genetic ; }, abstract = {The emergence of novelties, as a generator of diversity, in the form and function of the organisms have long puzzled biologists. The study of the developmental process and the anatomical properties of an organism provides scarce information into the means by which its morphology evolved. Some have argued that the very nature of novelty is believed to be linked to the evolution of gene regulation, rather than to the emergence of new structural genes. In order to gain further insight into the evolution of novelty and diversity, we describe a simple computational model of gene regulation that controls the development of locomotive multicellular organisms through a fixed set of simple structural genes. Organisms, modeled as two-dimensional spring networks, are simulated in a virtual environment to evaluate their steering skills for path-following. Proposed as a behavior-finding problem, this fitness function guides an evolutionary algorithm that produces structures whose function is well-adapted to the environment (i.e., good path-followers). We show that, despite the fixed simple set of structural genes, the evolution of gene regulation yields a rich variety of body plans, including symmetries, body segments, and modularity, resulting in a diversity of original behaviors to follow a simple path. These results suggest that the sole variation in the regulation of gene expression is a sufficient condition for the emergence of novelty and diversity.}, } @article {pmid20833319, year = {2010}, author = {Li, H and Johnson, AD}, title = {Evolution of transcription networks--lessons from yeasts.}, journal = {Current biology : CB}, volume = {20}, number = {17}, pages = {R746-53}, pmid = {20833319}, issn = {1879-0445}, support = {R01 GM037049/GM/NIGMS NIH HHS/United States ; R01 GM037049-26/GM/NIGMS NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; *Gene Regulatory Networks ; *Transcription, Genetic ; Yeasts/*genetics ; }, abstract = {That regulatory evolution is important in generating phenotypic diversity was suggested soon after the discovery of gene regulation. In the past few decades, studies in animals have provided a number of examples in which phenotypic changes can be traced back to specific alterations in transcriptional regulation. Recent advances in DNA sequencing technology and functional genomics have stimulated a new wave of investigation in simple model organisms. In particular, several genome-wide comparative analyses of transcriptional circuits across different yeast species have been performed. These studies have revealed that transcription networks are remarkably plastic: large scale rewiring in which target genes move in and out of regulons through changes in cis-regulatory sequences appears to be a general phenomenon. Transcription factor substitution and the formation of new combinatorial interactions are also important contributors to the rewiring. In several cases, a transition through intermediates with redundant regulatory programs has been suggested as a mechanism through which rewiring can occur without a loss in fitness. Because the basic features of transcriptional regulation are deeply conserved, we speculate that large scale rewiring may underlie the evolution of complex phenotypes in multi-cellular organisms; if so, such rewiring may leave traceable changes in the genome from which the genetic basis of functional innovation can be detected.}, } @article {pmid20832353, year = {2010}, author = {Worden, AZ and Allen, AE}, title = {The voyage of the microbial eukaryote.}, journal = {Current opinion in microbiology}, volume = {13}, number = {5}, pages = {652-660}, doi = {10.1016/j.mib.2010.08.001}, pmid = {20832353}, issn = {1879-0364}, mesh = {Biodiversity ; Epigenomics ; Eukaryota/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Genetics, Microbial ; }, abstract = {Although genome data from unicellular marine eukaryotes is sparse, sequences from several supergroups have initiated an era of genome-enabled research aimed at understanding gene function, evolution, and adaptation in non-traditional model protists. Trends in genomic content within and between different lineages are emerging, including phylogenetically anomalous patterns, sometimes resulting from horizontal gene transfer. Some such genes have nutrient uptake and metabolism roles suggesting that bacterial and eukaryotic microbes have similar cellular-mineral-environmental constraints. Many 'accessory genome' components are of unknown function, but low gene copy numbers combined with small genomes make protists ideal for systems biology. Cultured and uncultured protists are providing insights to ecology, ancestral features and the role of cooption in development of complex traits. Various protists harbor features important in sexuality and multicellularity once believed to have originated in metazoans or other multicellular taxa.}, } @article {pmid20830555, year = {2010}, author = {Weiland, N and Löscher, C and Metzger, R and Schmitz, R}, title = {Construction and screening of marine metagenomic libraries.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {668}, number = {}, pages = {51-65}, doi = {10.1007/978-1-60761-823-2_3}, pmid = {20830555}, issn = {1940-6029}, mesh = {Bacteria/*genetics ; DNA/analysis/isolation & purification ; DNA, Ribosomal/analysis/classification/isolation & purification ; *Gene Library ; Humans ; *Metagenome ; Metagenomics/*methods ; Phylogeny ; Seawater/*microbiology ; }, abstract = {Marine microbial communities are highly diverse and have evolved during extended evolutionary processes of physiological adaptations under the influence of a variety of ecological conditions and selection pressures. They harbor an enormous diversity of microbes with still unknown and probably new physiological characteristics. Besides, the surfaces of marine multicellular organisms are typically covered by a consortium of epibiotic bacteria and act as barriers, where diverse interactions between microorganisms and hosts take place. Thus, microbial diversity in the water column of the oceans and the microbial consortia on marine tissues of multicellular organisms are rich sources for isolating novel bioactive compounds and genes. Here we describe the sampling, construction of large-insert metagenomic libraries from marine habitats and exemplarily one function based screen of metagenomic clones.}, } @article {pmid20829787, year = {2010}, author = {Eldar, A and Elowitz, MB}, title = {Functional roles for noise in genetic circuits.}, journal = {Nature}, volume = {467}, number = {7312}, pages = {167-173}, pmid = {20829787}, issn = {1476-4687}, support = {P50 GM068763/GM/NIGMS NIH HHS/United States ; R01 GM079771/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01GM079771/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Physiological Phenomena ; *Gene Expression Regulation ; *Gene Regulatory Networks ; Humans ; Models, Genetic ; }, abstract = {The genetic circuits that regulate cellular functions are subject to stochastic fluctuations, or 'noise', in the levels of their components. Noise, far from just a nuisance, has begun to be appreciated for its essential role in key cellular activities. Noise functions in both microbial and eukaryotic cells, in multicellular development, and in evolution. It enables coordination of gene expression across large regulons, as well as probabilistic differentiation strategies that function across cell populations. At the longest timescales, noise may facilitate evolutionary transitions. Here we review examples and emerging principles that connect noise, the architecture of the gene circuits in which it is present, and the biological functions it enables. We further indicate some of the important challenges and opportunities going forward.}, } @article {pmid20818735, year = {2010}, author = {Rea, SL and Graham, BH and Nakamaru-Ogiso, E and Kar, A and Falk, MJ}, title = {Bacteria, yeast, worms, and flies: exploiting simple model organisms to investigate human mitochondrial diseases.}, journal = {Developmental disabilities research reviews}, volume = {16}, number = {2}, pages = {200-218}, pmid = {20818735}, issn = {1940-5529}, support = {K08 DK073545/DK/NIDDK NIH HHS/United States ; K08 HD044808/HD/NICHD NIH HHS/United States ; R01 HD065858/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*genetics ; Caenorhabditis elegans/*genetics ; DNA Mutational Analysis ; DNA, Mitochondrial/genetics ; *Disease Models, Animal ; Drosophila melanogaster/*genetics ; Humans ; Mitochondrial Diseases/*genetics ; *Models, Biological ; *Models, Genetic ; Saccharomyces cerevisiae/*genetics ; }, abstract = {The extensive conservation of mitochondrial structure, composition, and function across evolution offers a unique opportunity to expand our understanding of human mitochondrial biology and disease. By investigating the biology of much simpler model organisms, it is often possible to answer questions that are unreachable at the clinical level. Here, we review the relative utility of four different model organisms, namely the bacterium Escherichia coli, the yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans, and the fruit fly Drosophila melanogaster, in studying the role of mitochondrial proteins relevant to human disease. E. coli are single cell, prokaryotic bacteria that have proven to be a useful model system in which to investigate mitochondrial respiratory chain protein structure and function. S. cerevisiae is a single-celled eukaryote that can grow equally well by mitochondrial-dependent respiration or by ethanol fermentation, a property that has proven to be a veritable boon for investigating mitochondrial functionality. C. elegans is a multicellular, microscopic worm that is organized into five major tissues and has proven to be a robust model animal for in vitro and in vivo studies of primary respiratory chain dysfunction and its potential therapies in humans. Studied for over a century, D. melanogaster is a classic metazoan model system offering an abundance of genetic tools and reagents that facilitates investigations of mitochondrial biology using both forward and reverse genetics. The respective strengths and limitations of each species relative to mitochondrial studies are explored. In addition, an overview is provided of major discoveries made in mitochondrial biology in each of these four model systems.}, } @article {pmid20818375, year = {2010}, author = {Liu, H and Takeda, S and Kumar, R and Westergard, TD and Brown, EJ and Pandita, TK and Cheng, EH and Hsieh, JJ}, title = {Phosphorylation of MLL by ATR is required for execution of mammalian S-phase checkpoint.}, journal = {Nature}, volume = {467}, number = {7313}, pages = {343-346}, pmid = {20818375}, issn = {1476-4687}, support = {R01 CA123232/CA/NCI NIH HHS/United States ; CA129537/CA/NCI NIH HHS/United States ; R01 CA119008-02/CA/NCI NIH HHS/United States ; R01 CA129537/CA/NCI NIH HHS/United States ; R01 CA119008-03/CA/NCI NIH HHS/United States ; R01 CA119008-05/CA/NCI NIH HHS/United States ; R01 CA119008-04/CA/NCI NIH HHS/United States ; R01 CA119008/CA/NCI NIH HHS/United States ; CA119008/CA/NCI NIH HHS/United States ; CA123232/CA/NCI NIH HHS/United States ; R01 CA119008-01/CA/NCI NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins/*metabolism ; Cell Line ; Chromatin/metabolism ; DNA Damage ; DNA Replication/physiology ; Genes, Dominant/genetics ; Genomic Instability/physiology ; Histone-Lysine N-Methyltransferase ; Histones/chemistry/metabolism ; Humans ; Leukemia/genetics ; Lysine/metabolism ; Methylation ; Mice ; Myeloid Progenitor Cells/metabolism ; Myeloid-Lymphoid Leukemia Protein/chemistry/deficiency/genetics/*metabolism ; Phosphorylation ; Phosphoserine/metabolism ; Protein Binding ; Protein Serine-Threonine Kinases/*metabolism ; S Phase/*physiology ; S-Phase Kinase-Associated Proteins/metabolism ; Signal Transduction ; Translocation, Genetic/genetics ; }, abstract = {Cell cycle checkpoints are implemented to safeguard the genome, avoiding the accumulation of genetic errors. Checkpoint loss results in genomic instability and contributes to the evolution of cancer. Among G1-, S-, G2- and M-phase checkpoints, genetic studies indicate the role of an intact S-phase checkpoint in maintaining genome integrity. Although the basic framework of the S-phase checkpoint in multicellular organisms has been outlined, the mechanistic details remain to be elucidated. Human chromosome-11 band-q23 translocations disrupting the MLL gene lead to poor prognostic leukaemias. Here we assign MLL as a novel effector in the mammalian S-phase checkpoint network and identify checkpoint dysfunction as an underlying mechanism of MLL leukaemias. MLL is phosphorylated at serine 516 by ATR in response to genotoxic stress in the S phase, which disrupts its interaction with, and hence its degradation by, the SCF(Skp2) E3 ligase, leading to its accumulation. Stabilized MLL protein accumulates on chromatin, methylates histone H3 lysine 4 at late replication origins and inhibits the loading of CDC45 to delay DNA replication. Cells deficient in MLL showed radioresistant DNA synthesis and chromatid-type genomic abnormalities, indicative of S-phase checkpoint dysfunction. Reconstitution of Mll(-/-) (Mll also known as Mll1) mouse embryonic fibroblasts with wild-type but not S516A or ΔSET mutant MLL rescues the S-phase checkpoint defects. Moreover, murine myeloid progenitor cells carrying an Mll-CBP knock-in allele that mimics human t(11;16) leukaemia show a severe radioresistant DNA synthesis phenotype. MLL fusions function as dominant negative mutants that abrogate the ATR-mediated phosphorylation/stabilization of wild-type MLL on damage to DNA, and thus compromise the S-phase checkpoint. Together, our results identify MLL as a key constituent of the mammalian DNA damage response pathway and show that deregulation of the S-phase checkpoint incurred by MLL translocations probably contributes to the pathogenesis of human MLL leukaemias.}, } @article {pmid20817718, year = {2011}, author = {Hulpiau, P and van Roy, F}, title = {New insights into the evolution of metazoan cadherins.}, journal = {Molecular biology and evolution}, volume = {28}, number = {1}, pages = {647-657}, doi = {10.1093/molbev/msq233}, pmid = {20817718}, issn = {1537-1719}, mesh = {Amino Acid Sequence ; Animals ; Cadherins/classification/*genetics/metabolism ; *Evolution, Molecular ; Humans ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; }, abstract = {Mining newly sequenced genomes of basal metazoan organisms reveals the evolutionary origin of modern protein families. Specific cell-cell adhesion and intracellular communication are key processes in multicellular animals, and members of the cadherin superfamily are essential players in these processes. Mammalian genomes contain over 100 genes belonging to this superfamily. By a combination of tBLASTn and profile hidden Markov model analyses, we made an exhaustive search for cadherins and compiled the cadherin repertoires in key organisms, including Branchiostoma floridae (amphioxus), the sea anemone Nematostella vectensis, and the placozoan Trichoplax adhaerens. Comparative analyses of multiple protein domains within known and novel cadherins enabled us to reconstruct the complex evolution in metazoa of this large superfamily. Five main cadherin branches are represented in the primitive metazoan Trichoplax: classical (CDH), flamingo (CELSR), dachsous (DCHS), FAT, and FAT-like. Classical cadherins, such as E-cadherin, arose from an Urmetazoan cadherin, which progressively lost N-terminal extracellular cadherin repeats, whereas its cytoplasmic domain, which binds the armadillo proteins p120ctn and β-catenin, remained quite conserved from placozoa to man. The origin of protocadherins predates the Bilateria and is likely rooted in an ancestral FAT cadherin. Several but not all protostomians lost protocadherins. The emergence of chordates coincided with a great expansion of the protocadherin repertoire. The evolution of ancient metazoan cadherins points to their unique and crucial roles in multicellular animal life.}, } @article {pmid20817460, year = {2010}, author = {Abedin, M and King, N}, title = {Diverse evolutionary paths to cell adhesion.}, journal = {Trends in cell biology}, volume = {20}, number = {12}, pages = {734-742}, pmid = {20817460}, issn = {1879-3088}, support = {R01 GM089977/GM/NIGMS NIH HHS/United States ; R01 GM089977-01/GM/NIGMS NIH HHS/United States ; R01 GM089977-02/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Cell Adhesion ; Eukaryota/cytology ; Extracellular Matrix ; Fungi/cytology ; Plant Cells ; }, abstract = {The morphological diversity of animals, fungi, plants, and other multicellular organisms stems from the fact that each lineage acquired multicellularity independently. A prerequisite for each origin of multicellularity was the evolution of mechanisms for stable cell-cell adhesion or attachment. Recent advances in comparative genomics and phylogenetics provide critical insights into the evolutionary foundations of cell adhesion. Reconstructing the evolution of cell junction proteins in animals and their unicellular relatives exemplifies the roles of co-option and innovation. Comparative studies of volvocine algae reveal specific molecular changes that accompanied the evolution of multicellularity in Volvox. Comparisons between animals and Dictyostelium show how commonalities and differences in the biology of unicellular ancestors influenced the evolution of adhesive mechanisms. Understanding the unicellular ancestry of cell adhesion helps illuminate the basic cell biology of multicellular development in modern organisms.}, } @article {pmid20816239, year = {2010}, author = {Fernandez-Sanchez, ME and Serman, F and Ahmadi, P and Farge, E}, title = {Mechanical induction in embryonic development and tumor growth integrative cues through molecular to multicellular interplay and evolutionary perspectives.}, journal = {Methods in cell biology}, volume = {98}, number = {}, pages = {295-321}, doi = {10.1016/S0091-679X(10)98012-6}, pmid = {20816239}, issn = {0091-679X}, mesh = {Animals ; Cell Communication/genetics/*physiology ; Cell Growth Processes/genetics/physiology ; Cell Transformation, Neoplastic/genetics/pathology ; Embryonic Development/genetics/*physiology ; *Evolution, Molecular ; Gene Regulatory Networks/*physiology ; Humans ; Mechanotransduction, Cellular/genetics/*physiology ; Models, Biological ; Neoplasms/genetics/*pathology/physiopathology ; }, abstract = {Embryonic development is a coordination of multicellular biochemical patterning and morphogenetic movements. Last decades revealed the close control of myosin-II-dependent biomechanical morphogenesis by patterning gene expression, with constant progress in the understanding of the underlying molecular mechanisms. Reversed control of developmental gene expression and of myosin-II patterning by the mechanical strains developed by morphogenetic movements was recently revealed at Drosophila gastrulation, through mechanotransduction processes involving the Armadillo/beta-catenin and the downstream of Fog Rho pathways. Here, we present the theoretical (simulations integrating the accumulated knowledge in the genetics of early embryonic development and morphogenesis) and the experimental (genetic and biophysical control of morphogenetic movements) tools having allowed the uncoupling of pure genetic inputs from pure mechanical inputs in the regulation of gene expression and myosin-II patterning. Specifically, we describe the innovative magnetic tweezers tools we have set up to measure and apply physiological strains and forces in vivo, from the inside of the tissue, to modulate and mimic morphogenetic movements in living embryos. We discuss mechanical induction incidence in tumor development and perspective in evolution.}, } @article {pmid20811343, year = {2010}, author = {Gilbert, DM}, title = {Evaluating genome-scale approaches to eukaryotic DNA replication.}, journal = {Nature reviews. Genetics}, volume = {11}, number = {10}, pages = {673-684}, pmid = {20811343}, issn = {1471-0064}, support = {P01 GM085354/GM/NIGMS NIH HHS/United States ; P01 GM085354-020002/GM/NIGMS NIH HHS/United States ; R01 GM083337/GM/NIGMS NIH HHS/United States ; R01 GM083337-03/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA Replication/*genetics ; Eukaryotic Cells/*metabolism ; Genome/genetics ; Genomics/*methods ; Humans ; Models, Genetic ; Replication Origin/*genetics ; Reproducibility of Results ; }, abstract = {Mechanisms regulating where and when eukaryotic DNA replication initiates remain a mystery. Recently, genome-scale methods have been brought to bear on this problem. The identification of replication origins and their associated proteins in yeasts is a well-integrated investigative tool, but corresponding data sets from multicellular organisms are scarce. By contrast, standardized protocols for evaluating replication timing have generated informative data sets for most eukaryotic systems. Here, I summarize the genome-scale methods that are most frequently used to analyse replication in eukaryotes, the kinds of questions each method can address and the technical hurdles that must be overcome to gain a complete understanding of the nature of eukaryotic replication origins.}, } @article {pmid20809310, year = {2010}, author = {Silahtaroglu, AN}, title = {LNA-FISH for detection of microRNAs in frozen sections.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {659}, number = {}, pages = {165-171}, doi = {10.1007/978-1-60761-789-1_11}, pmid = {20809310}, issn = {1940-6029}, mesh = {Animals ; *Frozen Sections ; Humans ; In Situ Hybridization, Fluorescence/*methods ; MicroRNAs/*metabolism ; Nucleic Acid Probes/metabolism ; Oligonucleotides/*metabolism ; }, abstract = {MicroRNAs (miRNAs) are small (approximately 22 nt) noncoding RNA molecules that regulate the expression of protein coding genes either by cleavage or translational repression. miRNAs comprise one of the most abundant classes of gene regulatory molecules in multicellular organisms. Yet, the function of miRNAs at the tissue, cell, and subcellular levels is still to be explored. Especially, determining spatial and temporal expression of miRNAs has been a challenge due to their short size and low expression. This protocol describes a fast and effective method for detection of miRNAs in frozen tissue sections using fluorescence in situ hybridization. The method employs the unique recognition power of locked nucleic acids as probes together with enhanced detection power of the tyramide signal amplification system for detection of miRNAs in frozen tissues of human and animal origin within a single day.}, } @article {pmid20800533, year = {2010}, author = {Finazzi, G and Moreau, H and Bowler, C}, title = {Genomic insights into photosynthesis in eukaryotic phytoplankton.}, journal = {Trends in plant science}, volume = {15}, number = {10}, pages = {565-572}, doi = {10.1016/j.tplants.2010.07.004}, pmid = {20800533}, issn = {1878-4372}, mesh = {Eukaryota/cytology/*genetics/*metabolism ; Genome ; *Photosynthesis ; Phytoplankton/classification/*genetics/*metabolism ; }, abstract = {The evolution of photosynthesis completely altered the biogeochemistry of our planet and permitted the evolution of more complex multicellular organisms. Curiously, terrestrial photosynthesis is carried out largely by green algae and their descendents the higher plants, whereas in the ocean the most abundant photosynthetic eukaryotes are microscopic and have red algal affiliations. Although primary productivity is approximately equal between the land and the ocean, the marine microbes represent less than 1% of the photosynthetic biomass found on land. This review focuses on this highly successful and diverse group of organisms collectively known as phytoplankton and reviews how insights from whole genome analyses have improved our understanding of the novel innovations employed by them to maximize photosynthetic efficiency in variable light environments.}, } @article {pmid20739317, year = {2011}, author = {Yokota, K and Sterner, RW}, title = {Trade-offs limiting the evolution of coloniality: ecological displacement rates used to measure small costs.}, journal = {Proceedings. Biological sciences}, volume = {278}, number = {1704}, pages = {458-463}, pmid = {20739317}, issn = {1471-2954}, mesh = {*Biological Evolution ; Cell Count ; Chlorophyta/*growth & development/metabolism/ultrastructure ; *Ecology ; Insect Hormones/metabolism ; Linear Models ; }, abstract = {Multicellular organisms that benefit from division of labour are presumably descended from colonial species that initially derived benefits from larger colony size, before the evolution of specialization. Life in a colony can have costs as well as benefits, but these can be hard to measure. We measured physiological costs to life in a colony using a novel method based on population dynamics, comparing growth rates of unicells and kairomone-induced colonies of a green alga Desmodesmus subspicatus against a reference co-occurring species. Coloniality negatively affected growth during the initial log growth phase, while no adverse effect was detected under nutrient-limited competitive conditions. The results point to costs associated with traits involved in rapid growth rather than those associated with efficient growth under resource scarcity. Some benefits of coloniality (e.g. defence from herbivory) may be different from when this trait evolved, but our approach shows how costs would have depended on conditions.}, } @article {pmid20738463, year = {2010}, author = {Saito-Nakano, Y and Nakahara, T and Nakano, K and Nozaki, T and Numata, O}, title = {Marked amplification and diversification of products of ras genes from rat brain, Rab GTPases, in the ciliates Tetrahymena thermophila and Paramecium tetraurelia.}, journal = {The Journal of eukaryotic microbiology}, volume = {57}, number = {5}, pages = {389-399}, doi = {10.1111/j.1550-7408.2010.00503.x}, pmid = {20738463}, issn = {1550-7408}, mesh = {Animals ; Brain/enzymology ; Evolution, Molecular ; *Gene Amplification ; *Genetic Variation ; Humans ; Molecular Sequence Data ; Multigene Family ; Paramecium tetraurelia/chemistry/classification/*enzymology/genetics ; Phylogeny ; Protozoan Proteins/chemistry/*genetics/metabolism ; Rats ; Sequence Alignment ; Tetrahymena thermophila/chemistry/classification/*enzymology/genetics ; rab GTP-Binding Proteins/chemistry/*genetics/metabolism ; }, abstract = {Small GTPase Rab (products of ras genes from rat brain) is a widely conserved molecular switch among eukaryotes and regulates membrane trafficking pathways. It is generally considered that the number of Rab encoded in the genome correlates with multicellularity; however, we found that unicellular ciliates Tetrahymena thermophila (Tt) and Paramecium tetraurelia (Pt) possess many more Rab genes in their genome than the 64 HsRab genes in the human genome. We succeeded in isolating 86 cDNA clones of 88 TtRab genes in the Tetrahymena genome. By comparing the amino acid sequence of Rab in humans and the budding yeast Saccharomyces cerevisiae, 42 TtRab belonged to subfamilies functionally characterized and designated as conventional Rab, while the remaining 44 TtRab were considered to be species-specific. To examine the diversity of Rab in ciliates, we searched for Rab genes in the genome database of P. tetraurelia. Overall, 229 PtRab genes were found and categorized as 157 conventional and 72 species-specific PtRab, respectively. Among them, nine PtRab genes showed high homology to seven TtRab, suggesting the conservation of ciliate-specific Rab. These data suggested that the range of Rab is markedly amplified and diversified in ciliates, which may support the elaborate cellular structures and vigorous phagocytosis of those organisms.}, } @article {pmid20737785, year = {2010}, author = {Dent, JA}, title = {The evolution of pentameric ligand-gated ion channels.}, journal = {Advances in experimental medicine and biology}, volume = {683}, number = {}, pages = {11-23}, doi = {10.1007/978-1-4419-6445-8_2}, pmid = {20737785}, issn = {0065-2598}, mesh = {Animals ; *Evolution, Molecular ; Genetic Variation ; Ion Channel Gating/*physiology ; Ion Channels/chemistry/*genetics/metabolism ; Ligands ; Synaptic Transmission/physiology ; }, abstract = {Fast, ionotropic neurotransmission mediated by ligand-gated ion channels is essential for timely behavioral responses in multicellular organisms. Metazoa employ more ionotropic neurotransmitters in more types of synapses, inhibitory or excitatory, than is generally appreciated. It is becoming increasingly clear that the adaptability of a single neurotransmitter receptor superfamily, the pentameric ligand-gated ion channels (pLGICs), makes the diversity in ionotropic neurotransmission possible. Modification ofa common pLGIC structure generates channels that are gated by ligands as different as protons, histamine or zinc and that pair common neurotransmitters with both cation and anion permeability. A phylogeny of the pLGIC gene family from representative metazoa suggests that pLGIC diversity is ancient and evolution of contemporary phyla was characterized by a surprising loss of pLGIC diversity. The pLGIC superfamily reveals aspects of early metazoan evolution, may help us identify novel neurotransmitters and can inform our exploration of structure/function relationships.}, } @article {pmid20736450, year = {2011}, author = {Hanada, K and Sawada, Y and Kuromori, T and Klausnitzer, R and Saito, K and Toyoda, T and Shinozaki, K and Li, WH and Hirai, MY}, title = {Functional compensation of primary and secondary metabolites by duplicate genes in Arabidopsis thaliana.}, journal = {Molecular biology and evolution}, volume = {28}, number = {1}, pages = {377-382}, pmid = {20736450}, issn = {1537-1719}, mesh = {Amino Acid Sequence ; Arabidopsis/*genetics/*metabolism ; *Evolution, Molecular ; Gene Knockdown Techniques ; *Genes, Duplicate ; *Genes, Plant ; Molecular Sequence Data ; }, abstract = {It is well known that knocking out a gene in an organism often causes no phenotypic effect. One possible explanation is the existence of duplicate genes; that is, the effect of knocking out a gene is compensated by a duplicate copy. Another explanation is the existence of alternative pathways. In terms of metabolic products, the relative roles of the two mechanisms have been extensively studied in yeast but not in any multi-cellular organisms. Here, to address the functional compensation of metabolic products by duplicate genes, we quantified 35 metabolic products from 1,976 genes in knockout mutants of Arabidopsis thaliana by a high-throughput Liquid chromatography-Mass spectrometer (LC-MS) analysis. We found that knocking out either a singleton gene or a duplicate gene with distant paralogs in the genome tends to induce stronger metabolic effects than knocking out a duplicate gene with a close paralog in the genome, indicating that only duplicate genes with close paralogs play a significant role in functional compensation for metabolic products in A. thaliana. To extend the analysis, we examined metabolic products with either high or low connectivity in a metabolic network. We found that the compensatory role of duplicate genes is less important when the metabolite has a high connectivity, indicating that functional compensation by alternative pathways is common in the case of high connectivity. In conclusion, recently duplicated genes play an important role in the compensation of metabolic products only when the number of alternative pathways is small.}, } @article {pmid20735476, year = {2010}, author = {Sapp, M and Parker, ER and Teal, LR and Schratzberger, M}, title = {Advancing the understanding of biogeography-diversity relationships of benthic microorganisms in the North Sea.}, journal = {FEMS microbiology ecology}, volume = {74}, number = {2}, pages = {410-429}, doi = {10.1111/j.1574-6941.2010.00957.x}, pmid = {20735476}, issn = {1574-6941}, mesh = {*Biodiversity ; Crenarchaeota/classification/genetics ; DNA, Archaeal/genetics ; DNA, Bacterial/genetics ; Deltaproteobacteria/classification/genetics ; Euryarchaeota/classification/genetics ; Gammaproteobacteria/classification/genetics ; Geologic Sediments/microbiology ; North Sea ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; *Water Microbiology ; }, abstract = {Knowledge on the spatial distribution of prokaryotic taxa is an essential basis to understand microbial diversity and the factors shaping its patterns. Large-scale patterns of faunal distribution are thought to be influenced by physical environmental factors, whereas smaller scale spatial heterogeneity is maintained by species-specific life-history characteristics, the quantity and quality of food sources and local disturbances including both natural and man-induced events. However, it is still not clear which environmental parameters control the diversity and community structure of sedimentary microorganisms mediating important ecosystem processes. In this study, multiscale patterns were elucidated at seven stations in the Oyster Ground, North Sea (54°4'N/4°E), 100 m to 11 km apart. These were related to biotic (e.g. multicellular organisms) and abiotic parameters (e.g. organic carbon content in the sediment) to establish the relationship between the distribution of both bacterial and archaeal communities and their environment. A relatively high variability was detected at all scales for bacterial and archaeal communities, both of which were controlled by different suites of biotic and abiotic environmental variables. The bacterial community consisted mainly of members belonging to the Gammaproteobacteria and the Fibrobacteres/Acidobacteria group. Members of the Deltaproteobacteria, Bacteroidetes and Actinobacteria also contributed to the bacterial community. Euryarchaeota formed the majority of archaeal phylotypes together with three phylotypes belonging to the Crenarchaeota.}, } @article {pmid20726010, year = {2010}, author = {Rainey, PB and Kerr, B}, title = {Cheats as first propagules: a new hypothesis for the evolution of individuality during the transition from single cells to multicellularity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {32}, number = {10}, pages = {872-880}, doi = {10.1002/bies.201000039}, pmid = {20726010}, issn = {1521-1878}, mesh = {*Biological Evolution ; Cell Division ; *Germ Cells ; Models, Genetic ; *Reproduction ; *Selection, Genetic ; }, abstract = {The emergence of individuality during the evolutionary transition from single cells to multicellularity poses a range of problems. A key issue is how variation in lower-level individuals generates a corporate (collective) entity with Darwinian characteristics. Of central importance to this process is the evolution of a means of collective reproduction, however, the evolution of a means of collective reproduction is not a trivial issue, requiring careful consideration of mechanistic details. Calling upon observations from experiments, we draw attention to proto-life cycles that emerge via unconventional routes and that transition, in single steps, individuality to higher levels. One such life cycle arises from conflicts among levels of selection and invokes cheats as a primitive germ line: it lays the foundation for collective reproduction, the basis of a self-policing system, the selective environment for the emergence of development, and hints at a plausible origin for a soma/germ line distinction.}, } @article {pmid20722725, year = {2011}, author = {Nedelcu, AM and Driscoll, WW and Durand, PM and Herron, MD and Rashidi, A}, title = {On the paradigm of altruistic suicide in the unicellular world.}, journal = {Evolution; international journal of organic evolution}, volume = {65}, number = {1}, pages = {3-20}, doi = {10.1111/j.1558-5646.2010.01103.x}, pmid = {20722725}, issn = {1558-5646}, mesh = {Adaptation, Biological ; Eukaryota/*cytology/*physiology ; Phylogeny ; Prokaryotic Cells/*cytology/*physiology ; }, abstract = {Altruistic suicide is best known in the context of programmed cell death (PCD) in multicellular individuals, which is understood as an adaptive process that contributes to the development and functionality of the organism. After the realization that PCD-like processes can also be induced in single-celled lineages, the paradigm of altruistic cell death has been extended to include these active cell death processes in unicellular organisms. Here, we critically evaluate the current conceptual framework and the experimental data used to support the notion of altruistic suicide in unicellular lineages, and propose new perspectives. We argue that importing the paradigm of altruistic cell death from multicellular organisms to explain active death in unicellular lineages has the potential to limit the types of questions we ask, thus biasing our understanding of the nature, origin, and maintenance of this trait. We also emphasize the need to distinguish between the benefits and the adaptive role of a trait. Lastly, we provide an alternative framework that allows for the possibility that active death in single-celled organisms is a maladaptive trait maintained as a byproduct of selection on pro-survival functions, but that could-under conditions in which kin/group selection can act-be co-opted into an altruistic trait.}, } @article {pmid20714396, year = {2010}, author = {Zani, BG and Edelman, ER}, title = {Cellular bridges: Routes for intercellular communication and cell migration.}, journal = {Communicative & integrative biology}, volume = {3}, number = {3}, pages = {215-220}, pmid = {20714396}, issn = {1942-0889}, support = {R01 GM049039/GM/NIGMS NIH HHS/United States ; }, abstract = {Cell-to-cell communication is the basis of all biology in multicellular organisms, allowing evolution of complex forms and viability in dynamic environments. Though biochemical interactions occur over distances, physical continuity remains the most direct means of cellular interactions. Cellular bridging through thin cytoplasmic channels-plasmodesmata in plants and tunneling nanotubes in animals-creates direct routes for transfer of signals and components, even pathogens, between cells. Recently, two new cellular connections, designated epithelial (EP) bridges, were discovered and found to be structurally distinct from other cellular channels. The first EP bridge type facilitates material transport between cells similar to plasmodesmata and tunneling nanotubes, the second EP bridge type mediates migration of cells between EP cell masses representing a novel form of cell migration. Here, we compare the structures and functions of EP bridges with other cellular channels and discuss biochemical and cellular interactions involved in EP bridge formation. Potential roles for EP bridges in health and disease are also presented.}, } @article {pmid20708707, year = {2010}, author = {Chen, W and Wang, Y and Li, W and Lin, H}, title = {Insulin-like growth factor binding protein-2 (IGFBP-2) in orange-spotted grouper, Epinephelus coioides: molecular characterization, expression profiles and regulation by 17β-estradiol in ovary.}, journal = {Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology}, volume = {157}, number = {4}, pages = {336-342}, doi = {10.1016/j.cbpb.2010.08.001}, pmid = {20708707}, issn = {1879-1107}, mesh = {Amino Acid Sequence ; Animals ; Cloning, Molecular ; Embryo, Nonmammalian/metabolism ; Estradiol/*pharmacology ; Female ; Fish Proteins/classification/*genetics/metabolism ; Gene Expression Regulation ; Insulin-Like Growth Factor Binding Protein 2/classification/*genetics/metabolism ; Molecular Sequence Data ; Ovary/drug effects/*metabolism ; Perciformes/embryology/*genetics/metabolism ; Phylogeny ; RNA, Messenger/metabolism ; Sequence Homology, Amino Acid ; Tissue Distribution ; }, abstract = {In the present study, a full-length cDNA encoding the insulin-like growth factor binding protein-2 (IGFBP-2) was cloned from the liver of orange-spotted grouper (Epinephelus coioides) by rapid amplification of cDNA ends technique. The IGFBP-2 cDNA sequence was 1413 bp long and had an open reading frame (ORF) of 813 bp encoding a predicted polypeptide of 270 amino acid residues. The deduced amino acid sequence contained a putative signal peptide of 22 amino acid residues resulting in a mature protein of 248 amino acids. Using semi-quantitative RT-PCR, tissue distribution pattern showed that IGFBP-2 mRNA was observed in all regions of brain with high levels, except lower levels in cerebellum and hypothalamus. In peripheral tissues, IGFBP-2 mRNA was most abundant in liver, although relatively high levels were observed in intestine, ovary and pituitary. Low or no IGFBP-2 mRNA expression was observed in other examined tissues. From the multicellular stage to the hatching stage, IGFBP-2 mRNA was expressed consecutively. Furthermore, 1 nM 17β-estradiol could inhibit the ovarian IGFBP-2 mRNA expression significantly in vitro. The mRNA expression and regulation profiles suggest that the IGFBP-2 may play important physiological roles in fish growth and reproduction, as well as cell growth and organ differentiation during the embryonic developmental stages.}, } @article {pmid20697207, year = {2010}, author = {Price, CM and Boltz, KA and Chaiken, MF and Stewart, JA and Beilstein, MA and Shippen, DE}, title = {Evolution of CST function in telomere maintenance.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {9}, number = {16}, pages = {3157-3165}, pmid = {20697207}, issn = {1551-4005}, support = {R01 GM065383/GM/NIGMS NIH HHS/United States ; F32 CA117846/CA/NCI NIH HHS/United States ; T32 CA117846/CA/NCI NIH HHS/United States ; GM041803/GM/NIGMS NIH HHS/United States ; F32 GM093635/GM/NIGMS NIH HHS/United States ; R01 GM088728/GM/NIGMS NIH HHS/United States ; GM065383/GM/NIGMS NIH HHS/United States ; R01 GM041803/GM/NIGMS NIH HHS/United States ; GM088728/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Cycle Proteins/chemistry/*metabolism ; Chromosomal Proteins, Non-Histone/chemistry/*metabolism ; Evolution, Molecular ; Humans ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; Shelterin Complex ; Telomere/*metabolism ; Telomere-Binding Proteins/chemistry/genetics/*metabolism ; }, abstract = {Telomeres consist of an elaborate, higher-order DNA architecture, and a suite of proteins that provide protection for the chromosome terminus by blocking inappropriate recombination and nucleolytic attack. In addition, telomeres facilitate telomeric DNA replication by physical interactions with telomerase and the lagging strand replication machinery. The prevailing view has been that two distinct telomere capping complexes evolved, shelterin in vertebrates and a trimeric complex comprised of Cdc13, Stn1 and Ten1 (CST) in yeast. The recent discovery of a CST-like complex in plants and humans raises new questions about the composition of telomeres and their regulatory mechanisms in multicellular eukaryotes. In this review we discuss the evolving functions and interactions of CST components and their contributions to chromosome end protection and DNA replication.}, } @article {pmid20693358, year = {2011}, author = {Kuwabara, T and Kawasaki, A and Uda, I and Sugai, A}, title = {Thermosipho globiformans sp. nov., an anaerobic thermophilic bacterium that transforms into multicellular spheroids with a defect in peptidoglycan formation.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {61}, number = {Pt 7}, pages = {1622-1627}, doi = {10.1099/ijs.0.025106-0}, pmid = {20693358}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gram-Negative Anaerobic Straight, Curved, and Helical Rods/*classification/genetics/isolation & purification ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Pacific Ocean ; Peptidoglycan/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; }, abstract = {An anaerobic rod-shaped thermophile was isolated from a hydrothermal vent at Suiyo Seamount, Izu-Bonin Arc, western Pacific Ocean, and was named strain MN14(T). The rods were gram-negative-staining, non-motile without flagella, 2-4 µm long and 0.5 µm wide, and divided by binary fission in the mid-exponential phase. The cells were surrounded by a sheath-like structure (toga) and occurred singly or in chains. Spheroids containing multiple cells were observed not only in the stationary phase, as previously observed for species of the order Thermotogales, but also from the early exponential phase. Transmission electron microscopy revealed that the peptidoglycan in rods partly disintegrated in the early growth phases and that the outer membrane of the spheroids was not completely lined with peptidoglycan. These findings suggested that the spheroids were formed from rods by the disintegration of peptidoglycan and subsequent inflation of the outer membrane. The spheroids eventually generated tiny cells in the periplasmic space, indicating a viviparous mode of proliferation in addition to binary fission. Strain MN14(T) grew at 40-75 °C, pH 5.0-8.2 and with 0.25-5.20 % (w/v) NaCl, with optimal growth occurring at 68 °C, pH 6.8 and with 2.5 % NaCl. The shortest doubling time was 24 min, assuming that the strain propagated only by binary fission. Elemental sulfur enhanced growth, but was not essential. Thiosulfate was not an electron acceptor for growth. The strain was a chemo-organotroph that grew on yeast extract as the sole growth substrate. Tryptone and starch supported its growth in the presence of yeast extract. The G+C content of the genomic DNA was 31.7 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that this strain belonged to the genus Thermosipho. No significant DNA-DNA hybridization was observed between the genomic DNA of strain MN14(T) and phylogenetically related species of the genus Thermosipho. Based on this evidence, strain MN14(T) is proposed to represent a novel species, named Thermosipho globiformans sp. nov. The species epithet globiformans reflects the formation of multicellular and reproductive spheroids by the novel strain. The type strain of this species is MN14(T) (= JCM 15059(T) = DSM 19918(T)).}, } @article {pmid20691101, year = {2010}, author = {Park, SG and Choi, SS}, title = {Expression breadth and expression abundance behave differently in correlations with evolutionary rates.}, journal = {BMC evolutionary biology}, volume = {10}, number = {}, pages = {241}, pmid = {20691101}, issn = {1471-2148}, mesh = {Animals ; Computational Biology/*methods ; *Evolution, Molecular ; Expressed Sequence Tags ; *Gene Expression ; Gene Expression Profiling/*methods ; Humans ; Mice ; Oligonucleotide Array Sequence Analysis ; }, abstract = {BACKGROUND: One of the main objectives of the molecular evolution and evolutionary systems biology field is to reveal the underlying principles that dictate protein evolutionary rates. Several studies argue that expression abundance is the most critical component in determining the rate of evolution, especially in unicellular organisms. However, the expression breadth also needs to be considered for multicellular organisms.

RESULTS: In the present paper, we analyzed the relationship between the two expression variables and rates using two different genome-scale expression datasets, microarrays and ESTs. A significant positive correlation between the expression abundance (EA) and expression breadth (EB) was revealed by Kendall's rank correlation tests. A novel random shuffling approach was applied for EA and EB to compare the correlation coefficients obtained from real data sets to those estimated based on random chance. A novel method called a Fixed Group Analysis (FGA) was designed and applied to investigate the correlations between expression variables and rates when one of the two expression variables was evenly fixed.

CONCLUSIONS: In conclusion, all of these analyses and tests consistently showed that the breadth rather than the abundance of gene expression is tightly linked with the evolutionary rate in multicellular organisms.}, } @article {pmid20686567, year = {2010}, author = {Srivastava, M and Simakov, O and Chapman, J and Fahey, B and Gauthier, ME and Mitros, T and Richards, GS and Conaco, C and Dacre, M and Hellsten, U and Larroux, C and Putnam, NH and Stanke, M and Adamska, M and Darling, A and Degnan, SM and Oakley, TH and Plachetzki, DC and Zhai, Y and Adamski, M and Calcino, A and Cummins, SF and Goodstein, DM and Harris, C and Jackson, DJ and Leys, SP and Shu, S and Woodcroft, BJ and Vervoort, M and Kosik, KS and Manning, G and Degnan, BM and Rokhsar, DS}, title = {The Amphimedon queenslandica genome and the evolution of animal complexity.}, journal = {Nature}, volume = {466}, number = {7307}, pages = {720-726}, pmid = {20686567}, issn = {1476-4687}, support = {R01 HG004164/HG/NHGRI NIH HHS/United States ; R01 HG004164-03/HG/NHGRI NIH HHS/United States ; R01 HG004164-04/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/genetics ; Cell Adhesion/genetics ; Cell Cycle/genetics ; Cell Polarity/genetics ; Cell Proliferation ; *Evolution, Molecular ; Genes/genetics ; Genome/*genetics ; Genomics ; Humans ; Immunity, Innate/genetics ; Models, Biological ; Neurons/metabolism ; Phosphotransferases/chemistry/genetics ; Phylogeny ; Porifera/anatomy & histology/cytology/*genetics/immunology ; Sequence Analysis, DNA ; Signal Transduction/genetics ; }, abstract = {Sponges are an ancient group of animals that diverged from other metazoans over 600 million years ago. Here we present the draft genome sequence of Amphimedon queenslandica, a demosponge from the Great Barrier Reef, and show that it is remarkably similar to other animal genomes in content, structure and organization. Comparative analysis enabled by the sequencing of the sponge genome reveals genomic events linked to the origin and early evolution of animals, including the appearance, expansion and diversification of pan-metazoan transcription factor, signalling pathway and structural genes. This diverse 'toolkit' of genes correlates with critical aspects of all metazoan body plans, and comprises cell cycle control and growth, development, somatic- and germ-cell specification, cell adhesion, innate immunity and allorecognition. Notably, many of the genes associated with the emergence of animals are also implicated in cancer, which arises from defects in basic processes associated with metazoan multicellularity.}, } @article {pmid20673351, year = {2010}, author = {Bittner, L and Halary, S and Payri, C and Cruaud, C and de Reviers, B and Lopez, P and Bapteste, E}, title = {Some considerations for analyzing biodiversity using integrative metagenomics and gene networks.}, journal = {Biology direct}, volume = {5}, number = {}, pages = {47}, pmid = {20673351}, issn = {1745-6150}, mesh = {Animals ; *Biodiversity ; Gene Regulatory Networks/*genetics ; Humans ; Metagenomics/*methods ; Models, Theoretical ; }, abstract = {BACKGROUND: Improving knowledge of biodiversity will benefit conservation biology, enhance bioremediation studies, and could lead to new medical treatments. However there is no standard approach to estimate and to compare the diversity of different environments, or to study its past, and possibly, future evolution.

We argue that there are two conditions for significant progress in the identification and quantification of biodiversity. First, integrative metagenomic studies - aiming at the simultaneous examination (or even better at the integration) of observations about the elements, functions and evolutionary processes captured by the massive sequencing of multiple markers - should be preferred over DNA barcoding projects and over metagenomic projects based on a single marker. Second, such metagenomic data should be studied with novel inclusive network-based approaches, designed to draw inferences both on the many units and on the many processes present in the environments.

TESTING THE HYPOTHESIS: We reached these conclusions through a comparison of the theoretical foundations of two molecular approaches seeking to assess biodiversity: metagenomics (mostly used on prokaryotes and protists) and DNA barcoding (mostly used on multicellular eukaryotes), and by pragmatic considerations of the issues caused by the 'species problem' in biodiversity studies.

Evolutionary gene networks reduce the risk of producing biodiversity estimates with limited explanatory power, biased either by unequal rates of LGT, or difficult to interpret due to (practical) problems caused by type I and type II grey zones. Moreover, these networks would easily accommodate additional (meta)transcriptomic and (meta)proteomic data.}, } @article {pmid20663212, year = {2010}, author = {Ueki, N and Matsunaga, S and Inouye, I and Hallmann, A}, title = {How 5000 independent rowers coordinate their strokes in order to row into the sunlight: phototaxis in the multicellular green alga Volvox.}, journal = {BMC biology}, volume = {8}, number = {}, pages = {103}, pmid = {20663212}, issn = {1741-7007}, mesh = {Flagella/*physiology ; Light ; Movement ; Photic Stimulation ; Phylogeny ; Volvox/genetics/*physiology/ultrastructure ; }, abstract = {BACKGROUND: The evolution of multicellular motile organisms from unicellular ancestors required the utilization of previously evolved tactic behavior in a multicellular context. Volvocine green algae are uniquely suited for studying tactic responses during the transition to multicellularity because they range in complexity from unicellular to multicellular genera. Phototactic responses are essential for these flagellates because they need to orientate themselves to receive sufficient light for photosynthesis, but how does a multicellular organism accomplish phototaxis without any known direct communication among cells? Several aspects of the photoresponse have previously been analyzed in volvocine algae, particularly in the unicellular alga Chlamydomonas.

RESULTS: In this study, the phototactic behavior in the spheroidal, multicellular volvocine green alga Volvox rousseletii (Volvocales, Chlorophyta) was analyzed. In response to light stimuli, not only did the flagella waveform and beat frequency change, but the effective stroke was reversed. Moreover, there was a photoresponse gradient from the anterior to the posterior pole of the spheroid, and only cells of the anterior hemisphere showed an effective response. The latter caused a reverse of the fluid flow that was confined to the anterior hemisphere. The responsiveness to light is consistent with an anterior-to-posterior size gradient of eyespots. At the posterior pole, the eyespots are tiny or absent, making the corresponding cells appear to be blind. Pulsed light stimulation of an immobilized spheroid was used to simulate the light fluctuation experienced by a rotating spheroid during phototaxis. The results demonstrated that in free-swimming spheroids, only those cells of the anterior hemisphere that face toward the light source reverse the beating direction in the presence of illumination; this behavior results in phototactic turning. Moreover, positive phototaxis is facilitated by gravitational forces. Under our conditions, V. rousseletii spheroids showed no negative phototaxis.

CONCLUSIONS: On the basis of our results, we developed a mechanistic model that predicts the phototactic behavior in V. rousseletii. The model involves photoresponses, periodically changing light conditions, morphological polarity, rotation of the spheroid, two modes of flagellar beating, and the impact of gravity. Our results also indicate how recently evolved multicellular organisms adapted the phototactic capabilities of their unicellular ancestors to multicellular life.}, } @article {pmid20659935, year = {2011}, author = {Kerr, AM and Baird, AH and Hughes, TP}, title = {Correlated evolution of sex and reproductive mode in corals (Anthozoa: Scleractinia).}, journal = {Proceedings. Biological sciences}, volume = {278}, number = {1702}, pages = {75-81}, pmid = {20659935}, issn = {1471-2954}, mesh = {Animals ; Anthozoa/*physiology ; *Biological Evolution ; Hermaphroditic Organisms/*physiology ; Phylogeny ; *Sex Characteristics ; Sexual Behavior, Animal/*physiology ; Time Factors ; }, abstract = {Sexuality and reproductive mode are two fundamental life-history traits that exhibit largely unexplained macroevolutionary patterns among the major groups of multicellular organisms. For example, the cnidarian class Anthozoa (corals and anemones) is mainly comprised of gonochoric (separate sex) brooders or spawners, while one order, Scleractinia (skeleton-forming corals), appears to be mostly hermaphroditic spawners. Here, using the most complete phylogeny of scleractinians, we reconstruct how evolutionary transitions between sexual systems (gonochorism versus hermaphrodism) and reproductive modes (brooding versus spawning) have generated large-scale taxonomic patterns in these characters. Hermaphrodites have independently evolved in three large, distantly related lineages consisting of mostly reef-building species. Reproductive mode in corals has evolved at twice the rate of sexuality, while the evolution of sexuality has been heavily biased: gonochorism is over 100 times more likely to be lost than gained, and can only be acquired by brooders. This circuitous evolutionary pathway accounts for the prevalence of hermaphroditic spawners among reef-forming scleractinians, despite their ancient gonochoric heritage.}, } @article {pmid20655980, year = {2010}, author = {Fontana, A}, title = {A hypothesis on the role of transposons.}, journal = {Bio Systems}, volume = {101}, number = {3}, pages = {187-193}, doi = {10.1016/j.biosystems.2010.07.002}, pmid = {20655980}, issn = {1872-8324}, mesh = {*Algorithms ; *Biological Evolution ; Cell Differentiation/*physiology ; DNA Transposable Elements/*physiology ; Embryonic Development/*physiology ; *Models, Biological ; }, abstract = {Genomic transposable elements, or transposons, are sequences of DNA that can move to different positions in the genome; in the process, they can cause chromosomal rearrengements and changes in gene expression. Despite their prevalence in the genomes of many species, their function is largely unknown: for this reason, they have been labelled "junk" DNA. "Epigenetic Tracking" is a model of development that, combined with a standard evolutionary algorithm, become an evo-devo method able to generate arbitrary shapes of any kind and complexity (in terms of number of cells, number of colours, etc.). The model of development has been also shown to be able to produce the artificial version of key biological phenomena such as the phenomenon of ageing, and the process of carcinogenesis. In this paper the evo-devo core of the method is explored and the result is a novel hypothesis on the biological role of transposons, according to which transposition in somatic cells during development drives cellular differentiation and transposition in germ cells is an indispensable tool to boost evolution. Thus, transposable elements, far from being "junk", have one of the most important roles in multicellular biology.}, } @article {pmid20636807, year = {2010}, author = {Hedrick, SM and Ch'en, IL and Alves, BN}, title = {Intertwined pathways of programmed cell death in immunity.}, journal = {Immunological reviews}, volume = {236}, number = {}, pages = {41-53}, pmid = {20636807}, issn = {1600-065X}, support = {R01 AI037988/AI/NIAID NIH HHS/United States ; R01 AI037988-14/AI/NIAID NIH HHS/United States ; R01 AI037988-15/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/*immunology ; Autophagy/*immunology ; Caspase 8/metabolism ; Cell Survival/immunology ; Humans ; Immunity/*immunology ; Necrosis/immunology ; Signal Transduction/*immunology ; T-Lymphocytes/immunology/metabolism ; }, abstract = {Programmed cell death (PCD) occurs widely in species from every kingdom of life. It has been shown to be an integral aspect of development in multicellular organisms, and it is an essential component of the immune response to infectious agents. An analysis of the phylogenetic origin of PCD now shows that it evolved independently several times, and it is fundamental to basic cellular physiology. Undoubtedly, PCD pervades all life at every scale of analysis. These considerations provide a backdrop for understanding the complexity of intertwined, but independent, cell death programs that operate within the immune system. In particular, the contributions of apoptosis, autophagy, and necrosis in the resolution of an immune response are considered.}, } @article {pmid20628610, year = {2010}, author = {Ran, L and Larsson, J and Vigil-Stenman, T and Nylander, JA and Ininbergs, K and Zheng, WW and Lapidus, A and Lowry, S and Haselkorn, R and Bergman, B}, title = {Genome erosion in a nitrogen-fixing vertically transmitted endosymbiotic multicellular cyanobacterium.}, journal = {PloS one}, volume = {5}, number = {7}, pages = {e11486}, pmid = {20628610}, issn = {1932-6203}, mesh = {Biological Evolution ; Cyanobacteria/*genetics/*growth & development ; Ferns/*microbiology ; Genome, Bacterial/*genetics ; Nitrogen Fixation/genetics/physiology ; Symbiosis/genetics/*physiology ; }, abstract = {BACKGROUND: An ancient cyanobacterial incorporation into a eukaryotic organism led to the evolution of plastids (chloroplasts) and subsequently to the origin of the plant kingdom. The underlying mechanism and the identities of the partners in this monophyletic event remain elusive.

To shed light on this evolutionary process, we sequenced the genome of a cyanobacterium residing extracellularly in an endosymbiosis with a plant, the water-fern Azolla filiculoides Lam. This symbiosis was selected as it has characters which make it unique among extant cyanobacterial plant symbioses: the cyanobacterium lacks autonomous growth and is vertically transmitted between plant generations. Our results reveal features of evolutionary significance. The genome is in an eroding state, evidenced by a large proportion of pseudogenes (31.2%) and a high frequency of transposable elements (approximately 600) scattered throughout the genome. Pseudogenization is found in genes such as the replication initiator dnaA and DNA repair genes, considered essential to free-living cyanobacteria. For some functional categories of genes pseudogenes are more prevalent than functional genes. Loss of function is apparent even within the 'core' gene categories of bacteria, such as genes involved in glycolysis and nutrient uptake. In contrast, serving as a critical source of nitrogen for the host, genes related to metabolic processes such as cell differentiation and nitrogen-fixation are well preserved.

CONCLUSIONS/SIGNIFICANCE: This is the first finding of genome degradation in a plant symbiont and phenotypically complex cyanobacterium and one of only a few extracellular endosymbionts described showing signs of reductive genome evolution. Our findings suggest an ongoing selective streamlining of this cyanobacterial genome which has resulted in an organism devoted to nitrogen fixation and devoid of autonomous growth. The cyanobacterial symbiont of Azolla can thus be considered at the initial phase of a transition from free-living organism to a nitrogen-fixing plant entity, a transition process which may mimic what drove the evolution of chloroplasts from a cyanobacterial ancestor.}, } @article {pmid20621960, year = {2010}, author = {Harcet, M and Roller, M and Cetković, H and Perina, D and Wiens, M and Müller, WE and Vlahovicek, K}, title = {Demosponge EST sequencing reveals a complex genetic toolkit of the simplest metazoans.}, journal = {Molecular biology and evolution}, volume = {27}, number = {12}, pages = {2747-2756}, pmid = {20621960}, issn = {1537-1719}, mesh = {Animals ; Base Sequence ; Comparative Genomic Hybridization ; *Evolution, Molecular ; *Expressed Sequence Tags ; Gene Expression Regulation ; Genome ; Molecular Sequence Data ; *Phylogeny ; Porifera/*genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; Suberites/*genetics ; }, abstract = {Sponges (Porifera) are among the simplest living and the earliest branching metazoans. They hold a pivotal role for studying genome evolution of the entire metazoan branch, both as an outgroup to Eumetazoa and as the closest branching phylum to the common ancestor of all multicellular animals (Urmetazoa). In order to assess the transcription inventory of sponges, we sequenced expressed sequence tag libraries of two demosponge species, Suberites domuncula and Lubomirskia baicalensis, and systematically analyzed the assembled sponge transcripts against their homologs from complete proteomes of six well-characterized metazoans--Nematostella vectensis, Caenorhabditis elegans, Drosophila melanogaster, Strongylocentrotus purpuratus, Ciona intestinalis, and Homo sapiens. We show that even the earliest metazoan species already have strikingly complex genomes in terms of gene content and functional repertoire and that the rich gene repertoire existed even before the emergence of true tissues, therefore further emphasizing the importance of gene loss and spatio-temporal changes in regulation of gene expression in shaping the metazoan genomes. Our findings further indicate that sponge and human genes generally show similarity levels higher than expected from their respective positions in metazoan phylogeny, providing direct evidence for slow rate of evolution in both "basal" and "apical" metazoan genome lineages. We propose that the ancestor of all metazoans had already had an unusually complex genome, thereby shifting the origins of genome complexity from Urbilateria to Urmetazoa.}, } @article {pmid20621190, year = {2010}, author = {Jørgensen, S and Baker, A and Møller, S and Nielsen, BS}, title = {Robust one-day in situ hybridization protocol for detection of microRNAs in paraffin samples using LNA probes.}, journal = {Methods (San Diego, Calif.)}, volume = {52}, number = {4}, pages = {375-381}, doi = {10.1016/j.ymeth.2010.07.002}, pmid = {20621190}, issn = {1095-9130}, mesh = {Animals ; Breast Neoplasms/chemistry ; Endopeptidase K/metabolism ; Humans ; In Situ Hybridization/*methods ; Mice ; MicroRNAs/*analysis ; *Oligonucleotides ; Paraffin Embedding ; RNA, Small Nuclear ; Sensitivity and Specificity ; }, abstract = {MicroRNAs (miRNAs) constitute a group of small non-coding RNA molecules generally 18-22 base-pairs in length. miRNAs are considered to be negative regulators of gene expression at the level of post-transcription and are important in normal physiological development, tissue homeostasis and disease. The cellular origin of individual microRNAs is of utmost importance for understanding their roles in molecular and biological processes, in multi-cellular and complex structured tissues. For the localization of miRNAs in clinical and experimental formalin-fixed and paraffin-embedded samples we have developed a simple and robust one-day in situ hybridization protocol based on the use of double digoxigenin (DIG)-labeled LNA-DNA chimeric probes. We show that the protocol enables analyses of specificity, and demonstrate the detection of miR-1, miR-21, miR-124, miR-126, miR-145, and miR-205 in human and murine paraffin material. The well established localization of these microRNAs makes them ideal for use as reference microRNAs when optimizing the microRNA in situ hybridization assay for a particular tissue and miRNA.}, } @article {pmid20617172, year = {2010}, author = {Flowers, JM and Li, SI and Stathos, A and Saxer, G and Ostrowski, EA and Queller, DC and Strassmann, JE and Purugganan, MD}, title = {Variation, sex, and social cooperation: molecular population genetics of the social amoeba Dictyostelium discoideum.}, journal = {PLoS genetics}, volume = {6}, number = {7}, pages = {e1001013}, pmid = {20617172}, issn = {1553-7404}, mesh = {Base Sequence ; Dictyostelium/classification/*genetics/growth & development/physiology ; Evolution, Molecular ; *Genetic Variation ; Linkage Disequilibrium ; Molecular Sequence Data ; North America ; Phylogeny ; Polymorphism, Single Nucleotide ; Species Specificity ; }, abstract = {Dictyostelium discoideum is a eukaryotic microbial model system for multicellular development, cell-cell signaling, and social behavior. Key models of social evolution require an understanding of genetic relationships between individuals across the genome or possibly at specific genes, but the nature of variation within D. discoideum is largely unknown. We re-sequenced 137 gene fragments in wild North American strains of D. discoideum and examined the levels and patterns of nucleotide variation in this social microbial species. We observe surprisingly low levels of nucleotide variation in D. discoideum across these strains, with a mean nucleotide diversity (pi) of 0.08%, and no strong population stratification among North American strains. We also do not find any clear relationship between nucleotide divergence between strains and levels of social dominance and kin discrimination. Kin discrimination experiments, however, show that strains collected from the same location show greater ability to distinguish self from non-self than do strains from different geographic areas. This suggests that a greater ability to recognize self versus non-self may arise among strains that are more likely to encounter each other in nature, which would lead to preferential formation of fruiting bodies with clonemates and may prevent the evolution of cheating behaviors within D. discoideum populations. Finally, despite the fact that sex has rarely been observed in this species, we document a rapid decay of linkage disequilibrium between SNPs, the presence of recombinant genotypes among natural strains, and high estimates of the population recombination parameter rho. The SNP data indicate that recombination is widespread within D. discoideum and that sex as a form of social interaction is likely to be an important aspect of the life cycle.}, } @article {pmid20616280, year = {2010}, author = {Prochnik, SE and Umen, J and Nedelcu, AM and Hallmann, A and Miller, SM and Nishii, I and Ferris, P and Kuo, A and Mitros, T and Fritz-Laylin, LK and Hellsten, U and Chapman, J and Simakov, O and Rensing, SA and Terry, A and Pangilinan, J and Kapitonov, V and Jurka, J and Salamov, A and Shapiro, H and Schmutz, J and Grimwood, J and Lindquist, E and Lucas, S and Grigoriev, IV and Schmitt, R and Kirk, D and Rokhsar, DS}, title = {Genomic analysis of organismal complexity in the multicellular green alga Volvox carteri.}, journal = {Science (New York, N.Y.)}, volume = {329}, number = {5988}, pages = {223-226}, pmid = {20616280}, issn = {1095-9203}, support = {R01 GM078376-02/GM/NIGMS NIH HHS/United States ; R01 GM078376-05/GM/NIGMS NIH HHS/United States ; 5 P41 LM006252/LM/NLM NIH HHS/United States ; R01 GM078376-04/GM/NIGMS NIH HHS/United States ; R01 GM078376-03/GM/NIGMS NIH HHS/United States ; R01 GM078376/GM/NIGMS NIH HHS/United States ; P41 LM006252/LM/NLM NIH HHS/United States ; R01 GM078376-01/GM/NIGMS NIH HHS/United States ; R01 GM078376-04S1/GM/NIGMS NIH HHS/United States ; }, mesh = {Algal Proteins/*chemistry/*genetics/metabolism ; Biological Evolution ; Chlamydomonas reinhardtii/cytology/*genetics/growth & development/physiology ; DNA, Algal/genetics ; Evolution, Molecular ; Extracellular Matrix Proteins/chemistry/genetics ; Genes ; *Genome ; Molecular Sequence Data ; Protein Structure, Tertiary ; Repetitive Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Species Specificity ; Synteny ; Volvox/cytology/*genetics/growth & development/physiology ; }, abstract = {The multicellular green alga Volvox carteri and its morphologically diverse close relatives (the volvocine algae) are well suited for the investigation of the evolution of multicellularity and development. We sequenced the 138-mega-base pair genome of V. carteri and compared its approximately 14,500 predicted proteins to those of its unicellular relative Chlamydomonas reinhardtii. Despite fundamental differences in organismal complexity and life history, the two species have similar protein-coding potentials and few species-specific protein-coding gene predictions. Volvox is enriched in volvocine-algal-specific proteins, including those associated with an expanded and highly compartmentalized extracellular matrix. Our analysis shows that increases in organismal complexity can be associated with modifications of lineage-specific proteins rather than large-scale invention of protein-coding capacity.}, } @article {pmid20616240, year = {2010}, author = {Pennisi, E}, title = {Genetics. Volvox genome shows it doesn't take much to be multicellular.}, journal = {Science (New York, N.Y.)}, volume = {329}, number = {5988}, pages = {128-129}, doi = {10.1126/science.329.5988.128-a}, pmid = {20616240}, issn = {1095-9203}, mesh = {Algal Proteins/chemistry/genetics ; Biological Evolution ; Chlamydomonas reinhardtii/cytology/*genetics/growth & development ; DNA, Algal/genetics ; Genes ; *Genome ; Repetitive Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Volvox/cytology/*genetics/growth & development ; }, } @article {pmid20603609, year = {2010}, author = {Calvo-Garrido, J and Carilla-Latorre, S and Kubohara, Y and Santos-Rodrigo, N and Mesquita, A and Soldati, T and Golstein, P and Escalante, R}, title = {Autophagy in Dictyostelium: genes and pathways, cell death and infection.}, journal = {Autophagy}, volume = {6}, number = {6}, pages = {686-701}, doi = {10.4161/auto.6.6.12513}, pmid = {20603609}, issn = {1554-8635}, mesh = {Animals ; *Autophagy ; Cell Death/genetics ; Dictyostelium/*cytology/genetics/*microbiology/ultrastructure ; Evolution, Molecular ; Genes, Protozoan/*genetics ; Models, Biological ; Signal Transduction/*genetics ; }, abstract = {The use of simple organisms to understand the molecular and cellular function of complex processes is instrumental for the rapid development of biomedical research. A remarkable example has been the discovery in S. cerevisiae of a group of proteins involved in the pathways of autophagy. Orthologues of these proteins have been identified in humans and experimental model organisms. Interestingly, some mammalian autophagy proteins do not seem to have homologues in yeast but are present in Dictyostelium, a social amoeba with two distinctive life phases, a unicellular stage in nutrient-rich conditions that differentiates upon starvation into a multicellular stage that depends on autophagy. This review focuses on the identification and annotation of the putative Dictyostelium autophagy genes and on the role of autophagy in development, cell death and infection by bacterial pathogens.}, } @article {pmid20598118, year = {2010}, author = {Henricson, A and Forslund, K and Sonnhammer, EL}, title = {Orthology confers intron position conservation.}, journal = {BMC genomics}, volume = {11}, number = {}, pages = {412}, pmid = {20598118}, issn = {1471-2164}, mesh = {Animals ; *Conserved Sequence ; Evolution, Molecular ; Humans ; Introns/*genetics ; Mice ; Proteins/chemistry/genetics/metabolism ; *Sequence Homology, Nucleic Acid ; }, abstract = {BACKGROUND: With the wealth of genomic data available it has become increasingly important to assign putative protein function through functional transfer between orthologs. Therefore, correct elucidation of the evolutionary relationships among genes is a critical task, and attempts should be made to further improve the phylogenetic inference by adding relevant discriminating features. It has been shown that introns can maintain their position over long evolutionary timescales. For this reason, it could be possible to use conservation of intron positions as a discriminating factor when assigning orthology. Therefore, we wanted to investigate whether orthologs have a higher degree of intron position conservation (IPC) compared to non-orthologous sequences that are equally similar in sequence.

RESULTS: To this end, we developed a new score for IPC and applied it to ortholog groups between human and six other species. For comparison, we also gathered the closest non-orthologs, meaning sequences close in sequence space, yet falling just outside the ortholog cluster. We found that ortholog-ortholog gene pairs on average have a significantly higher degree of IPC compared to ortholog-closest non-ortholog pairs. Also pairs of inparalogs were found to have a higher IPC score than inparalog-closest non-inparalog pairs. We verified that these differences can not simply be attributed to the generally higher sequence identity of the ortholog-ortholog and the inparalog-inparalog pairs. Furthermore, we analyzed the agreement between IPC score and the ortholog score assigned by the InParanoid algorithm, and found that it was consistently high for all species comparisons. In a minority of cases, the IPC and InParanoid score ranked inparalogs differently. These represent cases where sequence and intron position divergence are discordant. We further analyzed the discordant clusters to identify any possible preference for protein functions by looking for enriched GO terms and Pfam protein domains. They were enriched for functions important for multicellularity, which implies a connection between shifts in intronic structure and the origin of multicellularity.

CONCLUSIONS: We conclude that orthologous genes tend to have more conserved intron positions compared to non-orthologous genes. As a consequence, our IPC score is useful as an additional discriminating factor when assigning orthology.}, } @article {pmid20596008, year = {2010}, author = {Donoghue, PC and Antcliffe, JB}, title = {Early life: Origins of multicellularity.}, journal = {Nature}, volume = {466}, number = {7302}, pages = {41-42}, pmid = {20596008}, issn = {1476-4687}, mesh = {Bacteria/cytology ; Ecosystem ; *Fossils ; Gabon ; Geologic Sediments/microbiology ; History, Ancient ; Oxygen/metabolism ; }, } @article {pmid20594288, year = {2010}, author = {Ciccarelli, FD}, title = {The (r)evolution of cancer genetics.}, journal = {BMC biology}, volume = {8}, number = {}, pages = {74}, pmid = {20594288}, issn = {1741-7007}, mesh = {Animals ; *Evolution, Molecular ; Genes, Neoplasm/*genetics ; *Genetic Variation ; Humans ; *Models, Genetic ; }, abstract = {The identification of an increasing number of cancer genes is opening up unexpected scenarios in cancer genetics. When analyzed for their systemic properties, these genes show a general fragility towards perturbation. A recent paper published in BMC Biology shows how the founder domains of known cancer genes emerged at two macroevolutionary transitions - the advent of the first cell and the transition to metazoan multicellularity. See research article http://www.biomedcentral.com/1741-7007/8/66.}, } @article {pmid20591532, year = {2010}, author = {Schaack, S and Gilbert, C and Feschotte, C}, title = {Promiscuous DNA: horizontal transfer of transposable elements and why it matters for eukaryotic evolution.}, journal = {Trends in ecology & evolution}, volume = {25}, number = {9}, pages = {537-546}, pmid = {20591532}, issn = {0169-5347}, support = {R01 GM077582/GM/NIGMS NIH HHS/United States ; R01 GM077582-04/GM/NIGMS NIH HHS/United States ; R01GM77582/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; Animals ; Bacteria/*genetics ; DNA/*genetics ; DNA Transposable Elements/*genetics/physiology ; *Evolution, Molecular ; Plants/*genetics ; }, abstract = {Horizontal transfer is the passage of genetic material between genomes by means other than parent-to-offspring inheritance. Although the transfer of genes is thought to be crucial in prokaryotic evolution, few instances of horizontal gene transfer have been reported in multicellular eukaryotes; instead, most cases involve transposable elements. With over 200 cases now documented, it is possible to assess the importance of horizontal transfer for the evolution of transposable elements and their host genomes. We review criteria for detecting horizontal transfers and examine recent examples of the phenomenon, shedding light on its mechanistic underpinnings, including the role of host-parasite interactions. We argue that the introduction of transposable elements by horizontal transfer in eukaryotic genomes has been a major force propelling genomic variation and biological innovation.}, } @article {pmid20587059, year = {2010}, author = {Bendich, AJ}, title = {Mitochondrial DNA, chloroplast DNA and the origins of development in eukaryotic organisms.}, journal = {Biology direct}, volume = {5}, number = {}, pages = {42}, pmid = {20587059}, issn = {1745-6150}, mesh = {Animals ; *Biological Evolution ; DNA, Chloroplast/*genetics ; DNA, Mitochondrial/*genetics ; Eukaryota/*genetics ; Models, Theoretical ; Plants/genetics ; }, abstract = {BACKGROUND: Several proposals have been made to explain the rise of multicellular life forms. An internal environment can be created and controlled, germ cells can be protected in novel structures, and increased organismal size allows a "division of labor" among cell types. These proposals describe advantages of multicellular versus unicellular organisms at levels of organization at or above the individual cell. I focus on a subsequent phase of evolution, when multicellular organisms initiated the process of development that later became the more complex embryonic development found in animals and plants. The advantage here is realized at the level of the mitochondrion and chloroplast.

HYPOTHESIS: The extreme instability of DNA in mitochondria and chloroplasts has not been widely appreciated even though it was first reported four decades ago. Here, I show that the evolutionary success of multicellular animals and plants can be traced to the protection of organellar DNA. Three stages are envisioned. Sequestration allowed mitochondria and chloroplasts to be placed in "quiet" germ line cells so that their DNA is not exposed to the oxidative stress produced by these organelles in "active" somatic cells. This advantage then provided Opportunity, a period of time during which novel processes arose for signaling within and between cells and (in animals) for cell-cell recognition molecules to evolve. Development then led to the enormous diversity of animals and plants.

IMPLICATIONS: The potency of a somatic stem cell is its potential to generate cell types other than itself, and this is a systems property. One of the biochemical properties required for stemness to emerge from a population of cells might be the metabolic quiescence that protects organellar DNA from oxidative stress.}, } @article {pmid20585548, year = {2010}, author = {Johnston, AJ and Kirioukhova, O and Barrell, PJ and Rutten, T and Moore, JM and Baskar, R and Grossniklaus, U and Gruissem, W}, title = {Dosage-sensitive function of retinoblastoma related and convergent epigenetic control are required during the Arabidopsis life cycle.}, journal = {PLoS genetics}, volume = {6}, number = {6}, pages = {e1000988}, pmid = {20585548}, issn = {1553-7404}, mesh = {Arabidopsis/cytology/*genetics/growth & development ; Cell Differentiation ; Cell Lineage ; *Epigenesis, Genetic ; *Gene Dosage ; Genome, Plant ; Germ Cells, Plant/metabolism ; Mutation ; Ploidies ; Retinoblastoma/*genetics ; }, abstract = {The plant life cycle alternates between two distinct multi-cellular generations, the reduced gametophytes and the dominant sporophyte. Little is known about how generation-specific cell fate, differentiation, and development are controlled by the core regulators of the cell cycle. In Arabidopsis, RETINOBLASTOMA RELATED (RBR), an evolutionarily ancient cell cycle regulator, controls cell proliferation, differentiation, and regulation of a subset of Polycomb Repressive Complex 2 (PRC2) genes and METHYLTRANSFERASE 1 (MET1) in the male and female gametophytes, as well as cell fate establishment in the male gametophyte. Here we demonstrate that RBR is also essential for cell fate determination in the female gametophyte, as revealed by loss of cell-specific marker expression in all the gametophytic cells that lack RBR. Maintenance of genome integrity also requires RBR, because diploid plants heterozygous for rbr (rbr/RBR) produce an abnormal portion of triploid offspring, likely due to gametic genome duplication. While the sporophyte of the diploid mutant plants phenocopied wild type due to the haplosufficiency of RBR, genetic analysis of tetraploid plants triplex for rbr (rbr/rbr/rbr/RBR) revealed that RBR has a dosage-dependent pleiotropic effect on sporophytic development, trichome differentiation, and regulation of PRC2 subunit genes CURLY LEAF (CLF) and VERNALIZATION 2 (VRN2), and MET1 in leaves. There were, however, no obvious cell cycle and cell proliferation defects in these plant tissues, suggesting that a single functional RBR copy in tetraploids is capable of maintaining normal cell division but is not sufficient for distinct differentiation and developmental processes. Conversely, in leaves of mutants in sporophytic PRC2 subunits, trichome differentiation was also affected and expression of RBR and MET1 was reduced, providing evidence for a RBR-PRC2-MET1 regulatory feedback loop involved in sporophyte development. Together, dosage-sensitive RBR function and its genetic interaction with PRC2 genes and MET1 must have been recruited during plant evolution to control distinct generation-specific cell fate, differentiation, and development.}, } @article {pmid20576891, year = {2010}, author = {Smith, J and Van Dyken, JD and Zee, PC}, title = {A generalization of Hamilton's rule for the evolution of microbial cooperation.}, journal = {Science (New York, N.Y.)}, volume = {328}, number = {5986}, pages = {1700-1703}, pmid = {20576891}, issn = {1095-9203}, support = {R01GM084238/GM/NIGMS NIH HHS/United States ; GM07690/GM/NIGMS NIH HHS/United States ; R01 GM079690/GM/NIGMS NIH HHS/United States ; T32GM007757/GM/NIGMS NIH HHS/United States ; R01 GM079690-01/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Genetic Fitness ; Genotype ; *Microbial Interactions ; Models, Biological ; Models, Statistical ; Myxococcus xanthus/genetics/*physiology ; Selection, Genetic ; Spores, Bacterial/physiology ; }, abstract = {Hamilton's rule states that cooperation will evolve if the fitness cost to actors is less than the benefit to recipients multiplied by their genetic relatedness. This rule makes many simplifying assumptions, however, and does not accurately describe social evolution in organisms such as microbes where selection is both strong and nonadditive. We derived a generalization of Hamilton's rule and measured its parameters in Myxococcus xanthus bacteria. Nonadditivity made cooperative sporulation remarkably resistant to exploitation by cheater strains. Selection was driven by higher-order moments of population structure, not relatedness. These results provide an empirically testable cooperation principle applicable to both microbes and multicellular organisms and show how nonlinear interactions among cells insulate bacteria against cheaters.}, } @article {pmid20574072, year = {2010}, author = {Une, Y and Shirota, K and Nomura, Y}, title = {Cardiac angioleiomyoma in 44 cattle in Japan (1982-2009).}, journal = {Veterinary pathology}, volume = {47}, number = {5}, pages = {923-930}, doi = {10.1177/0300985810375055}, pmid = {20574072}, issn = {1544-2217}, mesh = {Angiomyoma/pathology/ultrastructure/*veterinary ; Animals ; Cattle ; Cattle Diseases/*pathology ; Heart Neoplasms/pathology/ultrastructure/*veterinary ; Immunohistochemistry/veterinary ; Microscopy, Electron, Transmission/veterinary ; Retrospective Studies ; }, abstract = {A retrospective study was performed on primary cardiac tumors found in 44 cattle during meat inspection in Japan, using histology, immunohistochemistry, and electron microscopy. The age of affected cattle ranged from 10 to 129 months; 82% were less than 3 years old. In 38 hearts, the tumor was solitary; the remaining 6 hearts had multiple masses. All tumors were subendocardial and involved the papillary muscles and/or cardiac valves. Two histologic patterns were recognized; both included giant cells. Pattern 1 was characterized by interlacing fascicles of spindle-shaped cells; pattern 2 resembled cavernous hemangioma. The 2 patterns coexisted and were linked by transitional zones. Given the immunohistochemical reactivity and ultrastructure, the spindle-shaped cells were identified as smooth muscle cells and the giant cells as endothelial cells. Single cell and multicellular angiogenesis by giant cells was observed. The tumors were classified as cardiac angioleiomyoma. Subendocardial multipotential mesenchymal cells, persistent tissue of the endocardial cushion, or valvular interstitial cells were suspected as the origin.}, } @article {pmid20567509, year = {2010}, author = {Treuner-Lange, A}, title = {The phosphatomes of the multicellular myxobacteria Myxococcus xanthus and Sorangium cellulosum in comparison with other prokaryotic genomes.}, journal = {PloS one}, volume = {5}, number = {6}, pages = {e11164}, pmid = {20567509}, issn = {1932-6203}, mesh = {*Genome, Archaeal ; *Genome, Bacterial ; *Genome, Fungal ; Myxococcales/genetics/*metabolism ; Myxococcus xanthus/genetics/*metabolism ; Phosphates/*metabolism ; Phylogeny ; Species Specificity ; }, abstract = {BACKGROUND: Analysis of the complete genomes from the multicellular myxobacteria Myxococcus xanthus and Sorangium cellulosum identified the highest number of eukaryotic-like protein kinases (ELKs) compared to all other genomes analyzed. High numbers of protein phosphatases (PPs) could therefore be anticipated, as reversible protein phosphorylation is a major regulation mechanism of fundamental biological processes.

METHODOLOGY: Here we report an intensive analysis of the phosphatomes of M. xanthus and S. cellulosum in which we constructed phylogenetic trees to position these sequences relative to PPs from other prokaryotic organisms.

PRINCIPAL FINDINGS: PREDOMINANT OBSERVATIONS WERE: (i) M. xanthus and S. cellulosum possess predominantly Ser/Thr PPs; (ii) S. cellulosum encodes the highest number of PP2c-type phosphatases so far reported for a prokaryotic organism; (iii) in contrast to M. xanthus only S. cellulosum encodes high numbers of SpoIIE-like PPs; (iv) there is a significant lack of synteny among M. xanthus and S. cellulosum, and (v) the degree of co-organization between kinase and phosphatase genes is extremely low in these myxobacterial genomes.

CONCLUSIONS: We conclude that there has been a greater expansion of ELKs than PPs in multicellular myxobacteria.}, } @article {pmid20566623, year = {2010}, author = {Silva, MT}, title = {Bacteria-induced phagocyte secondary necrosis as a pathogenicity mechanism.}, journal = {Journal of leukocyte biology}, volume = {88}, number = {5}, pages = {885-896}, doi = {10.1189/jlb.0410205}, pmid = {20566623}, issn = {1938-3673}, mesh = {Animals ; Apoptosis ; Autolysis ; Bacterial Infections/*pathology ; Bass ; Necrosis/*pathology ; Phagocytes/microbiology/*pathology ; Phagocytosis ; Signal Transduction ; Virulence ; }, abstract = {Triggering of phagocyte apoptosis is a major virulence mechanism used by some successful bacterial pathogens. A central issue in the apoptotic death context is that fully developed apoptosis results in necrotic cell autolysis (secondary necrosis) with release of harmful cell components. In multicellular animals, this occurs when apoptosing cells are not removed by scavengers, mainly macrophages. Secondary necrotic lysis of neutrophils and macrophages may occur in infection when extensive phagocyte apoptosis is induced by bacterial cytotoxins and removal of apoptosing phagocytes is defective because the apoptotic process exceeds the available scavenging capacity or targets macrophages directly. Induction of phagocyte secondary necrosis is an important pathogenic mechanism, as it combines the pathogen evasion from phagocyte antimicrobial activities and the release of highly cytotoxic molecules, particularly of neutrophil origin, such as neutrophil elastase. This pathogenicity mechanism therefore promotes the unrestricted multiplication of the pathogen and contributes directly to the pathology of several necrotizing infections, where extensive apoptosis and necrosis of macrophages and neutrophils are present. Here, examples of necrotizing infectious diseases, where phagocyte secondary necrosis is implicated, are reviewed.}, } @article {pmid20565538, year = {2010}, author = {Funayama, N and Nakatsukasa, M and Mohri, K and Masuda, Y and Agata, K}, title = {Piwi expression in archeocytes and choanocytes in demosponges: insights into the stem cell system in demosponges.}, journal = {Evolution & development}, volume = {12}, number = {3}, pages = {275-287}, doi = {10.1111/j.1525-142X.2010.00413.x}, pmid = {20565538}, issn = {1525-142X}, mesh = {Animals ; Base Sequence ; DNA Primers ; Porifera/*genetics ; RNA, Messenger/genetics ; RNA-Induced Silencing Complex/*genetics ; Stem Cells/*cytology ; }, abstract = {Little is known about the stem cells of organisms early in metazoan evolution. To characterize the stem cell system in demosponges, we identified Piwi homologs of a freshwater sponge, Ephydatia fluviatilis, as candidate stem cell (archeocyte) markers. EfPiwiA mRNA was expressed in cells with archeocyte cell morphological features. We demonstrated that these EfPiwiA-expressing cells were indeed stem cells by showing their ability to proliferate, as indicated by BrdU-incorporation, and to differentiate, as indicated by the coexpression of EfPiwiA with cell-lineage-specific genes in presumptive committed archeocytes. EfPiwiA mRNA expression was maintained in mature choanocytes forming chambers, in contrast to the transition of gene expression from EfPiwiA to cell-lineage-specific markers during archeocyte differentiation into other cell types. Choanocytes are food-entrapping cells with morphological features similar to those of choanoflagellates (microvillus collar and a flagellum). Their known abilities to transform into archeocytes under specific circumstances and to give rise to gametes (mostly sperm) indicate that even when they are fully differentiated, choanocytes maintain pluripotent stem cell-like potential. Based on the specific expression of EfPiwiA in archeocytes and choanocytes, combined with previous studies, we propose that both archeocytes and choanocytes are components of the demosponge stem cell system. We discuss the possibility that choanocytes might represent the ancestral stem cells, whereas archeocytes might represent stem cells that further evolved in ancestral multicellular organisms.}, } @article {pmid20553352, year = {2010}, author = {Nakada, T and Nozaki, H and Tomita, M}, title = {Another origin of coloniality in volvocaleans: the phylogenetic position of Pyrobotrys arnoldi (Spondylomoraceae, Volvocales).}, journal = {The Journal of eukaryotic microbiology}, volume = {57}, number = {4}, pages = {379-382}, doi = {10.1111/j.1550-7408.2010.00488.x}, pmid = {20553352}, issn = {1550-7408}, mesh = {Chlorophyta/*classification/genetics/growth & development/isolation & purification ; DNA, Algal/genetics ; DNA, Ribosomal/genetics ; Evolution, Molecular ; Molecular Sequence Data ; *Phylogeny ; }, abstract = {Colonial volvocaleans (Chlorophyceae) are used as a standard model of multicellular evolution. However, the phylogenetic position of the colonial volvocalean family Spondylomoraceae has yet to be resolved. To examine this, the molecular phylogenies of Pyrobotrys stellata and Pyrobotrys squarrosa were analyzed using combined 18S rRNA, RUBISCO large subunit, and P700 chl a-apoprotein A2 gene sequences. In the phylogenetic trees, Pyrobotrys belonged to the clade Caudivolvoxa and was not closely related to other colonial volvocalean flagellates. The results indicate that colony formation of Spondylomoraceae independently evolved from unicellular volvocaleans. The phylogenetic position of problematic "Pascherina tetras" SAG 159-1 was also analyzed.}, } @article {pmid20550938, year = {2010}, author = {Tian, Y and Li, Z and Hu, W and Ren, H and Tian, E and Zhao, Y and Lu, Q and Huang, X and Yang, P and Li, X and Wang, X and Kovács, AL and Yu, L and Zhang, H}, title = {C. elegans screen identifies autophagy genes specific to multicellular organisms.}, journal = {Cell}, volume = {141}, number = {6}, pages = {1042-1055}, doi = {10.1016/j.cell.2010.04.034}, pmid = {20550938}, issn = {1097-4172}, mesh = {Animals ; *Autophagy ; Caenorhabditis elegans/cytology/embryology/*genetics/physiology ; Caenorhabditis elegans Proteins/genetics ; Cytoplasmic Granules/metabolism ; Lysosomes/metabolism ; Mutation ; Phagosomes/metabolism ; }, abstract = {The molecular understanding of autophagy has originated almost exclusively from yeast genetic studies. Little is known about essential autophagy components specific to higher eukaryotes. Here we perform genetic screens in C. elegans and identify four metazoan-specific autophagy genes, named epg-2, -3, -4, and -5. Genetic analysis reveals that epg-2, -3, -4, and -5 define discrete genetic steps of the autophagy pathway. epg-2 encodes a coiled-coil protein that functions in specific autophagic cargo recognition. Mammalian homologs of EPG-3/VMP1, EPG-4/EI24, and EPG-5/mEPG5 are essential for starvation-induced autophagy. VMP1 regulates autophagosome formation by controlling the duration of omegasomes. EI24 and mEPG5 are required for formation of degradative autolysosomes. This study establishes C. elegans as a multicellular genetic model to delineate the autophagy pathway and provides mechanistic insights into the metazoan-specific autophagic process.}, } @article {pmid20548941, year = {2010}, author = {Gavrilets, S}, title = {Rapid transition towards the Division of Labor via evolution of developmental plasticity.}, journal = {PLoS computational biology}, volume = {6}, number = {6}, pages = {e1000805}, pmid = {20548941}, issn = {1553-7358}, support = {R01 GM056693/GM/NIGMS NIH HHS/United States ; GM56693/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; Cell Differentiation/*physiology ; Cell Survival ; Computational Biology/methods ; Evolution, Molecular ; Fertility ; Germ Cells/*growth & development ; Insecta ; *Models, Biological ; }, abstract = {A crucial step in several major evolutionary transitions is the division of labor between components of the emerging higher-level evolutionary unit. Examples include the separation of germ and soma in simple multicellular organisms, appearance of multiple cell types and organs in more complex organisms, and emergence of casts in eusocial insects. How the division of labor was achieved in the face of selfishness of lower-level units is controversial. I present a simple mathematical model describing the evolutionary emergence of the division of labor via developmental plasticity starting with a colony of undifferentiated cells and ending with completely differentiated multicellular organisms. I explore how the plausibility and the dynamics of the division of labor depend on its fitness advantage, mutation rate, costs of developmental plasticity, and the colony size. The model shows that the transition to differentiated multicellularity, which has happened many times in the history of life, can be achieved relatively easily. My approach is expandable in a number of directions including the emergence of multiple cell types, complex organs, or casts of eusocial insects.}, } @article {pmid20547848, year = {2010}, author = {Stajich, JE and Wilke, SK and Ahrén, D and Au, CH and Birren, BW and Borodovsky, M and Burns, C and Canbäck, B and Casselton, LA and Cheng, CK and Deng, J and Dietrich, FS and Fargo, DC and Farman, ML and Gathman, AC and Goldberg, J and Guigó, R and Hoegger, PJ and Hooker, JB and Huggins, A and James, TY and Kamada, T and Kilaru, S and Kodira, C and Kües, U and Kupfer, D and Kwan, HS and Lomsadze, A and Li, W and Lilly, WW and Ma, LJ and Mackey, AJ and Manning, G and Martin, F and Muraguchi, H and Natvig, DO and Palmerini, H and Ramesh, MA and Rehmeyer, CJ and Roe, BA and Shenoy, N and Stanke, M and Ter-Hovhannisyan, V and Tunlid, A and Velagapudi, R and Vision, TJ and Zeng, Q and Zolan, ME and Pukkila, PJ}, title = {Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom Coprinopsis cinerea (Coprinus cinereus).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {107}, number = {26}, pages = {11889-11894}, pmid = {20547848}, issn = {1091-6490}, support = {R01 HG004164-04/HG/NHGRI NIH HHS/United States ; HG004164/HG/NHGRI NIH HHS/United States ; HG00783/HG/NHGRI NIH HHS/United States ; R01 HG004164/HG/NHGRI NIH HHS/United States ; R01 HG000783/HG/NHGRI NIH HHS/United States ; GM43930/GM/NIGMS NIH HHS/United States ; R01 GM043930/GM/NIGMS NIH HHS/United States ; }, mesh = {Base Sequence ; Chromosome Mapping ; Chromosomes, Fungal/*genetics ; Coprinus/cytology/*genetics/growth & development ; Cytochrome P-450 Enzyme System/genetics ; DNA Primers/genetics ; *Evolution, Molecular ; Fungal Proteins/genetics ; Gene Duplication ; Genome, Fungal ; Meiosis/genetics ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Protein Kinases/genetics ; RNA, Fungal/genetics ; Recombination, Genetic ; Retroelements/genetics ; }, abstract = {The mushroom Coprinopsis cinerea is a classic experimental model for multicellular development in fungi because it grows on defined media, completes its life cycle in 2 weeks, produces some 10(8) synchronized meiocytes, and can be manipulated at all stages in development by mutation and transformation. The 37-megabase genome of C. cinerea was sequenced and assembled into 13 chromosomes. Meiotic recombination rates vary greatly along the chromosomes, and retrotransposons are absent in large regions of the genome with low levels of meiotic recombination. Single-copy genes with identifiable orthologs in other basidiomycetes are predominant in low-recombination regions of the chromosome. In contrast, paralogous multicopy genes are found in the highly recombining regions, including a large family of protein kinases (FunK1) unique to multicellular fungi. Analyses of P450 and hydrophobin gene families confirmed that local gene duplications drive the expansions of paralogous copies and the expansions occur in independent lineages of Agaricomycotina fungi. Gene-expression patterns from microarrays were used to dissect the transcriptional program of dikaryon formation (mating). Several members of the FunK1 kinase family are differentially regulated during sexual morphogenesis, and coordinate regulation of adjacent duplications is rare. The genomes of C. cinerea and Laccaria bicolor, a symbiotic basidiomycete, share extensive regions of synteny. The largest syntenic blocks occur in regions with low meiotic recombination rates, no transposable elements, and tight gene spacing, where orthologous single-copy genes are overrepresented. The chromosome assembly of C. cinerea is an essential resource in understanding the evolution of multicellularity in the fungi.}, } @article {pmid20546090, year = {2010}, author = {Buttery, NJ and Thompson, CR and Wolf, JB}, title = {Complex genotype interactions influence social fitness during the developmental phase of the social amoeba Dictyostelium discoideum.}, journal = {Journal of evolutionary biology}, volume = {23}, number = {8}, pages = {1664-1671}, doi = {10.1111/j.1420-9101.2010.02032.x}, pmid = {20546090}, issn = {1420-9101}, support = {G0900069/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Dictyostelium/genetics/growth & development/*physiology ; Genotype ; *Models, Genetic ; Phenotype ; Spores, Protozoan/physiology ; }, abstract = {When individuals interact, phenotypic variation can be partitioned into direct genetic effects (DGEs) of the individuals' own genotypes, indirect genetic effects (IGEs) of their social partners' genotypes and epistatic interactions between the genotypes of interacting individuals ('genotype-by-genotype (GxG) epistasis'). These components can all play important roles in evolutionary processes, but few empirical studies have examined their importance. The social amoeba Dictyostelium discoideum provides an ideal system to measure these effects during social interactions and development. When starved, free-living amoebae aggregate and differentiate into a multicellular fruiting body with a dead stalk that holds aloft viable spores. By measuring interactions among a set of natural strains, we quantify DGEs, IGEs and GxG epistasis affecting spore formation. We find that DGEs explain most of the phenotypic variance (57.6%) whereas IGEs explain a smaller (13.3%) but highly significant component. Interestingly, GxG epistasis explains nearly a quarter of the variance (23.0%), highlighting the complex nature of genotype interactions. These results demonstrate the large impact that social interactions can have on development and suggest that social effects should play an important role in developmental evolution in this system.}, } @article {pmid20534560, year = {2010}, author = {Drescher, K and Goldstein, RE and Tuval, I}, title = {Fidelity of adaptive phototaxis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {107}, number = {25}, pages = {11171-11176}, pmid = {20534560}, issn = {1091-6490}, support = {BB/F021844/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Biological Evolution ; Eukaryota/*physiology ; Gene Expression Regulation, Plant ; Kinetics ; *Light ; *Light Signal Transduction ; Models, Biological ; Models, Statistical ; Models, Theoretical ; Photochemistry/methods ; Plant Physiological Phenomena ; Time Factors ; }, abstract = {Along the evolutionary path from single cells to multicellular organisms with a central nervous system are species of intermediate complexity that move in ways suggesting high-level coordination, yet have none. Instead, organisms of this type possess many autonomous cells endowed with programs that have evolved to achieve concerted responses to environmental stimuli. Here experiment and theory are used to develop a quantitative understanding of how cells of such organisms coordinate to achieve phototaxis, by using the colonial alga Volvox carteri as a model. It is shown that the surface somatic cells act as individuals but are orchestrated by their relative position in the spherical extracellular matrix and their common photoresponse function to achieve colony-level coordination. Analysis of models that range from the minimal to the biologically faithful shows that, because the flagellar beating displays an adaptive down-regulation in response to light, the colony needs to spin around its swimming direction and that the response kinetics and natural spinning frequency of the colony appear to be mutually tuned to give the maximum photoresponse. These models further predict that the phototactic ability decreases dramatically when the colony does not spin at its natural frequency, a result confirmed by phototaxis assays in which colony rotation was slowed by increasing the fluid viscosity.}, } @article {pmid20523129, year = {2010}, author = {Pires, N and Dolan, L}, title = {Early evolution of bHLH proteins in plants.}, journal = {Plant signaling & behavior}, volume = {5}, number = {7}, pages = {911-912}, pmid = {20523129}, issn = {1559-2324}, support = {BBS/E/J/0000A218/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Basic-helix-loop-helix (bHLH) proteins are a large family of eukaryotic transcription factors. In plants, they have been shown to be key regulators of a diverse array of developmental and metabolic pathways. We have recently shown that the diversity of bHLH proteins in angiosperms is ancient. Most of the bHLH subfamilies present in seed plants such as Arabidopsis thaliana and Oryza sativa are also present in early diverging groups of land plants, including mosses and lycophytes. In contrast, the diversity of bHLH proteins is much lower in chlorophytes (green algae) and red algae. This suggests that the bHLH family underwent a large expansion before or soon after the appearance of the first land plants, but has subsequently remained relatively conserved throughout the evolution of plants on land. These observations support the developing paradigm that land plants (and other complex multicellular organisms) have evolved largely through the recruitment and reorganization of ancient gene regulatory networks.}, } @article {pmid20520714, year = {2010}, author = {Cock, JM and Sterck, L and Rouzé, P and Scornet, D and Allen, AE and Amoutzias, G and Anthouard, V and Artiguenave, F and Aury, JM and Badger, JH and Beszteri, B and Billiau, K and Bonnet, E and Bothwell, JH and Bowler, C and Boyen, C and Brownlee, C and Carrano, CJ and Charrier, B and Cho, GY and Coelho, SM and Collén, J and Corre, E and Da Silva, C and Delage, L and Delaroque, N and Dittami, SM and Doulbeau, S and Elias, M and Farnham, G and Gachon, CM and Gschloessl, B and Heesch, S and Jabbari, K and Jubin, C and Kawai, H and Kimura, K and Kloareg, B and Küpper, FC and Lang, D and Le Bail, A and Leblanc, C and Lerouge, P and Lohr, M and Lopez, PJ and Martens, C and Maumus, F and Michel, G and Miranda-Saavedra, D and Morales, J and Moreau, H and Motomura, T and Nagasato, C and Napoli, CA and Nelson, DR and Nyvall-Collén, P and Peters, AF and Pommier, C and Potin, P and Poulain, J and Quesneville, H and Read, B and Rensing, SA and Ritter, A and Rousvoal, S and Samanta, M and Samson, G and Schroeder, DC and Ségurens, B and Strittmatter, M and Tonon, T and Tregear, JW and Valentin, K and von Dassow, P and Yamagishi, T and Van de Peer, Y and Wincker, P}, title = {The Ectocarpus genome and the independent evolution of multicellularity in brown algae.}, journal = {Nature}, volume = {465}, number = {7298}, pages = {617-621}, pmid = {20520714}, issn = {1476-4687}, support = {P18266/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; REI20579/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Algal Proteins/*genetics ; Animals ; *Biological Evolution ; Eukaryota ; Evolution, Molecular ; Genome/*genetics ; Molecular Sequence Data ; Phaeophyta/*cytology/*genetics/metabolism ; Phylogeny ; Pigments, Biological/biosynthesis ; Signal Transduction/genetics ; }, abstract = {Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related. These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae, closely related to the kelps (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic approaches to explore these and other aspects of brown algal biology further.}, } @article {pmid20520609, year = {2010}, author = {Gómez, JM and Verdú, M and Perfectti, F}, title = {Ecological interactions are evolutionarily conserved across the entire tree of life.}, journal = {Nature}, volume = {465}, number = {7300}, pages = {918-921}, pmid = {20520609}, issn = {1476-4687}, mesh = {Animals ; Biological Evolution ; *Ecosystem ; Host-Parasite Interactions ; *Phylogeny ; Symbiosis/*physiology ; }, abstract = {Ecological interactions are crucial to understanding both the ecology and the evolution of organisms. Because the phenotypic traits regulating species interactions are largely a legacy of their ancestors, it is widely assumed that ecological interactions are phylogenetically conserved, with closely related species interacting with similar partners. However, the existing empirical evidence is inadequate to appropriately evaluate the hypothesis of phylogenetic conservatism in ecological interactions, because it is both ecologically and taxonomically biased. In fact, most studies on the evolution of ecological interactions have focused on specialized organisms, such as some parasites or insect herbivores, belonging to a limited subset of the overall tree of life. Here we study the evolution of host use in a large and diverse group of interactions comprising both specialist and generalist acellular, unicellular and multicellular organisms. We show that, as previously found for specialized interactions, generalized interactions can be evolutionarily conserved. Significant phylogenetic conservatism of interaction patterns was equally likely to occur in symbiotic and non-symbiotic interactions, as well as in mutualistic and antagonistic interactions. Host-use differentiation among species was higher in phylogenetically conserved clades, irrespective of their generalization degree and taxonomic position within the tree of life. Our findings strongly suggest a shared pattern in the organization of biological systems through evolutionary time, mediated by marked conservatism of ecological interactions among taxa.}, } @article {pmid20514130, year = {2009}, author = {Kilfoil, ML and Lasko, P and Abouheif, E}, title = {Stochastic variation: from single cells to superorganisms.}, journal = {HFSP journal}, volume = {3}, number = {6}, pages = {379-385}, pmid = {20514130}, issn = {1955-205X}, abstract = {Observed phenotype often fails to correspond with genotype. Although it is well established that uncontrolled genetic modifier effects and environmental variability can affect phenotype, stochastic variation in gene expression can also contribute to phenotypic differences. Here we examine recent work that has provided insights into how fundamental physical properties of living cells, and the probabilistic nature of the chemical reactions that underlie gene expression, introduce noise. We focus on instances in which a stochastic decision initiates an event in the development of a multicellular organism and how that decision can be subsequently fixed. We present an example indicating that a similar interplay between an initial stochastic decision and subsequent fixation may underlie the regulation of reproduction in social insects. We argue, therefore, that stochasticity affects biological processes from the single-gene scale through to the complex organization of an ant colony, and represents a largely neglected component of phenotypic variation and evolution.}, } @article {pmid20512319, year = {2010}, author = {Andersland, K and Jølle, GF and Sand, O and Haug, TM}, title = {Peptide pheromone plantaricin a produced by Lactobacillus plantarum permeabilizes liver and kidney cells.}, journal = {The Journal of membrane biology}, volume = {235}, number = {2}, pages = {121-129}, pmid = {20512319}, issn = {1432-1424}, mesh = {Animals ; Bacteriocins/*metabolism ; Cells, Cultured ; Chlorocebus aethiops ; Cytophotometry ; Electrophysiology ; Epithelial Cells/metabolism/microbiology ; Humans ; Kidney/*cytology ; Lactobacillus plantarum/growth & development/*metabolism ; Liver/*cytology ; Male ; Rats ; Rats, Wistar ; Vero Cells/metabolism/microbiology ; }, abstract = {Certain antimicrobial peptides from multicellular animals kill a variety of tumor cells at concentrations not affecting normal eukaryotic cells. Recently, it was reported that also plantaricin A (PlnA), which is a peptide pheromone with strain-specific antibacterial activity produced by Lactobacillus plantarum, permeabilizes cancerous rat pituitary cells (GH(4) cells), whereas normal rat anterior pituitary cells are resistant to the peptide. To examine whether the preferential permeabilization of cancerous cells is a general feature of PlnA, we studied its effect on primary cultures of cells from rat liver (hepatocytes, endothelial, and Kupffer cells) and rat kidney cortex, as well as two epithelial cell lines of primate kidney origin (Vero cells from green monkey and human Caki-2 cells). The Vero cell line is derived from normal cells, whereas the Caki-2 cell line is derived from a cancerous tumor. The membrane effects were studied by patch clamp recordings and microfluorometric (fura-2) monitoring of the cytosolic concentrations of Ca(2+) ([Ca(2+)](i)) and fluorophore. In all the tested cell types except Kupffer cells, exposure to 10-100 microM PlnA induced a nearly instant permeabilization of the membrane, indicated by the following criteria: increased membrane conductance, membrane depolarization, increased [Ca(2+)](i), and diffusional loss of fluorophore from the cytosol. At a concentration of 5 microM, PlnA had no effect on any of the cell types. The Kupffer cells were permeabilized by 500 microM PlnA. We conclude that the permeabilizing effect of PlnA is not restricted to cancerous cells.}, } @article {pmid20497285, year = {2010}, author = {Brown, MW and Silberman, JD and Spiegel, FW}, title = {A morphologically simple species of Acrasis (Heterolobosea, Excavata), Acrasis helenhemmesae n. sp.}, journal = {The Journal of eukaryotic microbiology}, volume = {57}, number = {4}, pages = {346-353}, doi = {10.1111/j.1550-7408.2010.00481.x}, pmid = {20497285}, issn = {1550-7408}, mesh = {Eukaryota/*classification/genetics/*growth & development/isolation & purification ; Molecular Sequence Data ; Phylogeny ; Trees/parasitology ; }, abstract = {In the course of a large-scale global survey of mycetozoans, amoeboid organisms that form fruiting bodies, a new species of Acrasis was discovered from several subtropical locales in Hawaii, Australia, Bermuda, and South Africa. We isolated four strains from dead, still attached, plant material, and one strain from attached bark of a tree. Each isolate forms simple uniseriate multicellular fruiting bodies typically consisting of two bottle-shaped, basal stalk cells and a chain of <20 spores. The isolate from Bermuda often forms dichotomous simple branches, each consisting of <10 spores. Amoebae from these new isolates are limax with eruptive pseudopodial formation and display rapid locomotion-characters indicative of amoebae in the excavate taxon Heterolobosea. These isolates form simpler fruiting bodies than is typical of the well-known Acrasis rosea. Although in the original description, A. rosea is known to form uniseriate fruiting bodies similar to our isolates, A. rosea isolates typically form more complex fruiting structures along side simple ones, but never strictly simple ones. Nuclear-encoded 18S rRNA gene phylogenies demonstrate that our five isolates form a highly supported clade that is sister to A. rosea. Given the differences both in gene sequences and fruiting body morphology between our isolates and A. rosea, we propose the new species, Acrasis helenhemmesae n. sp.}, } @article {pmid20494562, year = {2010}, author = {Gao, X and Zhang, X and Yang, X}, title = {Morphological apoptotic characteristics of the post-meiotic micronuclei in Paramecium caudatum.}, journal = {European journal of protistology}, volume = {46}, number = {3}, pages = {243-250}, doi = {10.1016/j.ejop.2010.04.004}, pmid = {20494562}, issn = {1618-0429}, mesh = {*Apoptosis ; Cell Nucleus/*metabolism ; Chromatin/metabolism ; DNA, Protozoan/*metabolism ; Fluorescent Dyes/metabolism ; *Meiosis ; Paramecium caudatum/*cytology ; Rosaniline Dyes/metabolism ; Staining and Labeling ; }, abstract = {In a previous study, the apoptotic degeneration of meiotic products outside the paroral region of Paramecium caudatum was indirectly demonstrated by means of "apofluor" staining. In this experiment, conjugating pairs and exconjugants of P. caudatum were stained with either "apofluor" or carbol fuchsin or both to find some direct evidence to demonstrate the apoptotic characteristics of this process. As a result, asynchronous meiotic nuclear degeneration was observed. Furthermore, a number of additional meiotic nuclei were found. Disintegrating/dividing meiotic nuclei outside the paroral region were observed, which might be the origin of these additional meiotic nuclei. Condensed chromatin and disintegrated chromatin attached to the nuclear membrane were also observed in degenerating nuclei, which are the typical morphological characteristics of apoptosis. Comparison of the cells stained by the above two methods indicated that "apofluor"-stained meiotic nuclei could not be detected by carbol fuchsin in some cells, which suggests a time lag between meiotic nuclear DNA degradation and their eventual disappearance. In this study, some direct evidence was found to show that the meiotic nuclear degeneration in P. caudatum is of apoptotic nature, which further confirmed our previous study (Yang et al. 2007) and indicated that morphological apoptotic characteristics discovered in multicellular organisms do exist in unicellular eukaryotic ciliate protozoa.}, } @article {pmid20493817, year = {2010}, author = {Busch, W and Miotk, A and Ariel, FD and Zhao, Z and Forner, J and Daum, G and Suzaki, T and Schuster, C and Schultheiss, SJ and Leibfried, A and Haubeiss, S and Ha, N and Chan, RL and Lohmann, JU}, title = {Transcriptional control of a plant stem cell niche.}, journal = {Developmental cell}, volume = {18}, number = {5}, pages = {849-861}, doi = {10.1016/j.devcel.2010.03.012}, pmid = {20493817}, issn = {1878-1551}, mesh = {Arabidopsis/*genetics/growth & development ; Arabidopsis Proteins/*genetics/*physiology ; Chromatin/genetics ; DNA-Binding Proteins/genetics ; *Gene Expression Regulation, Plant ; Genome, Plant ; Genome-Wide Association Study ; Homeodomain Proteins/genetics/*physiology ; Homeostasis ; Meristem/genetics/physiology ; Plant Stems/physiology ; Protein Serine-Threonine Kinases ; Receptor Protein-Tyrosine Kinases/genetics ; Transcription Factors/genetics ; *Transcription, Genetic ; }, abstract = {Despite the independent evolution of multicellularity in plants and animals, the basic organization of their stem cell niches is remarkably similar. Here, we report the genome-wide regulatory potential of WUSCHEL, the key transcription factor for stem cell maintenance in the shoot apical meristem of the reference plant Arabidopsis thaliana. WUSCHEL acts by directly binding to at least two distinct DNA motifs in more than 100 target promoters and preferentially affects the expression of genes with roles in hormone signaling, metabolism, and development. Striking examples are the direct transcriptional repression of CLAVATA1, which is part of a negative feedback regulation of WUSCHEL, and the immediate regulation of transcriptional repressors of the TOPLESS family, which are involved in auxin signaling. Our results shed light on the complex transcriptional programs required for the maintenance of a dynamic and essential stem cell niche.}, } @article {pmid20492640, year = {2010}, author = {Domazet-Loso, T and Tautz, D}, title = {Phylostratigraphic tracking of cancer genes suggests a link to the emergence of multicellularity in metazoa.}, journal = {BMC biology}, volume = {8}, number = {}, pages = {66}, pmid = {20492640}, issn = {1741-7007}, mesh = {Animals ; Computational Biology ; *Evolution, Molecular ; Genes, Neoplasm/*genetics ; Genomics/methods ; Humans ; *Models, Genetic ; *Phylogeny ; Protein Structure, Tertiary/*genetics ; }, abstract = {BACKGROUND: Phylostratigraphy is a method used to correlate the evolutionary origin of founder genes (that is, functional founder protein domains) of gene families with particular macroevolutionary transitions. It is based on a model of genome evolution that suggests that the origin of complex phenotypic innovations will be accompanied by the emergence of such founder genes, the descendants of which can still be traced in extant organisms. The origin of multicellularity can be considered to be a macroevolutionary transition, for which new gene functions would have been required. Cancer should be tightly connected to multicellular life since it can be viewed as a malfunction of interaction between cells in a multicellular organism. A phylostratigraphic tracking of the origin of cancer genes should, therefore, also provide insights into the origin of multicellularity.

RESULTS: We find two strong peaks of the emergence of cancer related protein domains, one at the time of the origin of the first cell and the other around the time of the evolution of the multicellular metazoan organisms. These peaks correlate with two major classes of cancer genes, the 'caretakers', which are involved in general functions that support genome stability and the 'gatekeepers', which are involved in cellular signalling and growth processes. Interestingly, this phylogenetic succession mirrors the ontogenetic succession of tumour progression, where mutations in caretakers are thought to precede mutations in gatekeepers.

CONCLUSIONS: A link between multicellularity and formation of cancer has often been predicted. However, this has not so far been explicitly tested. Although we find that a significant number of protein domains involved in cancer predate the origin of multicellularity, the second peak of cancer protein domain emergence is, indeed, connected to a phylogenetic level where multicellular animals have emerged. The fact that we can find a strong and consistent signal for this second peak in the phylostratigraphic map implies that a complex multi-level selection process has driven the transition to multicellularity.}, } @article {pmid20491665, year = {2010}, author = {Maple, J and Møller, SG}, title = {The complexity and evolution of the plastid-division machinery.}, journal = {Biochemical Society transactions}, volume = {38}, number = {3}, pages = {783-788}, doi = {10.1042/BST0380783}, pmid = {20491665}, issn = {1470-8752}, mesh = {Biological Evolution ; Chlorophyta/cytology/metabolism ; Plant Cells ; *Plants/metabolism ; Plastids/*physiology/ultrastructure ; Symbiosis ; }, abstract = {Plastids are vital organelles, fulfilling important metabolic functions that greatly influence plant growth and productivity. In order to both regulate and harness the metabolic output of plastids, it is vital that the process of plastid division is carefully controlled. This is essential, not only to ensure persistence in dividing plant cells and that optimal numbers of plastids are obtained in specialized cell types, but also to allow the cell to act in response to developmental signals and environmental changes. How this control is exerted by the host nucleus has remained elusive. Plastids evolved by endosymbiosis and during the establishment of a permanent endosymbiosis they retained elements of the bacterial cell-division machinery. Through evolution the photosynthetic eukaryotes have increased dramatically in complexity, from single-cell green algae to multicellular non-vascular and vascular plants. Reflected with this is an increasing complexity of the division machinery and recent findings also suggest increasing complexity in the molecular mechanisms used by the host cell to control the process of plastid division. In the present paper, we explore the current understanding of the process of plastid division at the molecular and cellular level, with particular respect to the evolution of the division machinery and levels of control exerted on the process.}, } @article {pmid20489016, year = {2010}, author = {Yu, YT and Yuan, X and Velicer, GJ}, title = {Adaptive evolution of an sRNA that controls Myxococcus development.}, journal = {Science (New York, N.Y.)}, volume = {328}, number = {5981}, pages = {993}, pmid = {20489016}, issn = {1095-9203}, support = {R01 GM079690-02/GM/NIGMS NIH HHS/United States ; R01 GM079690-01/GM/NIGMS NIH HHS/United States ; R01 GM079690-04/GM/NIGMS NIH HHS/United States ; R01 GM079690-03/GM/NIGMS NIH HHS/United States ; R01 GM079690/GM/NIGMS NIH HHS/United States ; GM079690/GM/NIGMS NIH HHS/United States ; R01 GM079690-05/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; *Evolution, Molecular ; Gene Deletion ; Genes, Bacterial ; Microbial Interactions ; Mutation ; Myxococcus xanthus/*genetics/*growth & development/physiology ; Phenotype ; RNA, Bacterial/chemistry/genetics/*physiology ; RNA, Untranslated/chemistry/genetics/*physiology ; Spores, Bacterial/growth & development ; }, abstract = {Small RNA (sRNA) molecules regulate a vast array of processes in biology, but evidence for adaptive evolution of sRNA sequences has been indirect. Here, we identify an sRNA, Pxr, that negatively regulates fruiting body development in Myxococcus xanthus. We further show that a spontaneous evolutionary mutation in Pxr abolished its regulatory function and thereby adaptively restored developmental proficiency to a socially defective M. xanthus cheater. In wild-type M. xanthus, development is initiated only upon starvation, but deletion of pxr allows development to proceed even while nutrients remain abundant. Thus, Pxr serves as a major checkpoint controlling the transition from growth to development in the myxobacteria. These findings show that an sRNA molecule governs a complex form of multicellular development in prokaryotes and directly demonstrate the ability of sRNA regulators to facilitate evolutionary adaptations of major phenotypic effect.}, } @article {pmid20481761, year = {2010}, author = {Deymier, PA and Eray, M and Deymier, MJ and Runge, K and Hoying, JB and Vasseur, JO}, title = {Architecture-dependent signal conduction in model networks of endothelial cells.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {81}, number = {4 Pt 1}, pages = {041915}, doi = {10.1103/PhysRevE.81.041915}, pmid = {20481761}, issn = {1550-2376}, mesh = {Calcium/metabolism ; Cell Communication ; Diffusion ; Endothelial Cells/*cytology/metabolism ; Feedback, Physiological ; Inositol 1,4,5-Trisphosphate/metabolism ; *Models, Biological ; *Signal Transduction ; }, abstract = {Signal conduction between endothelial cells along the walls of vessels appears to play an important role in circulatory function. A recently developed approach to calculate analytically the spectrum of propagating compositional waves in models of multicellular architectures is extended to study putative signal conduction dynamics across networks of endothelial cells. Here, compositional waves originate from negative feedback loops, such as between Ca2+ and inositol triphosphate (IP3) in endothelial cells, and are shaped by their connection topologies. We consider models of networks constituted of a main chain of endothelial cells and multiple side chains. The resulting transmission spectra encode information concerning the position and size of the side branches in the form of gaps. This observation suggests that endothelial cell networks may be able to "communicate" information regarding long-range order in their architecture.}, } @article {pmid20479976, year = {2010}, author = {Smith, VJ and Desbois, AP and Dyrynda, EA}, title = {Conventional and unconventional antimicrobials from fish, marine invertebrates and micro-algae.}, journal = {Marine drugs}, volume = {8}, number = {4}, pages = {1213-1262}, pmid = {20479976}, issn = {1660-3397}, mesh = {Animals ; Anti-Infective Agents/chemistry/isolation & purification/*pharmacology ; Biological Products/isolation & purification/*pharmacology ; Biotechnology/*methods ; Eukaryota/metabolism ; Fishes/metabolism ; Humans ; Invertebrates/metabolism ; }, abstract = {All eukaryotic organisms, single-celled or multi-cellular, produce a diverse array of natural anti-infective agents that, in addition to conventional antimicrobial peptides, also include proteins and other molecules often not regarded as part of the innate defences. Examples range from histones, fatty acids, and other structural components of cells to pigments and regulatory proteins. These probably represent very ancient defence factors that have been re-used in new ways during evolution. This review discusses the nature, biological role in host protection and potential biotechnological uses of some of these compounds, focusing on those from fish, marine invertebrates and marine micro-algae.}, } @article {pmid20479784, year = {2010}, author = {Lasi, M and Pauly, B and Schmidt, N and Cikala, M and Stiening, B and Käsbauer, T and Zenner, G and Popp, T and Wagner, A and Knapp, RT and Huber, AH and Grunert, M and Söding, J and David, CN and Böttger, A}, title = {The molecular cell death machinery in the simple cnidarian Hydra includes an expanded caspase family and pro- and anti-apoptotic Bcl-2 proteins.}, journal = {Cell research}, volume = {20}, number = {7}, pages = {812-825}, doi = {10.1038/cr.2010.66}, pmid = {20479784}, issn = {1748-7838}, mesh = {Amino Acid Sequence ; Animals ; Apoptosis/*drug effects ; Caspases/*genetics/metabolism ; Hydra/*genetics/metabolism ; Proto-Oncogene Proteins c-bcl-2/*genetics ; Two-Hybrid System Techniques ; bcl-2 Homologous Antagonist-Killer Protein/*genetics ; }, abstract = {The fresh water polyp Hydra belongs to the phylum Cnidaria, which diverged from the metazoan lineage before the appearance of bilaterians. In order to understand the evolution of apoptosis in metazoans, we have begun to elucidate the molecular cell death machinery in this model organism. Based on ESTs and the whole Hydra genome assembly, we have identified 15 caspases. We show that one is activated during apoptosis, four have characteristics of initiator caspases with N-terminal DED, CARD or DD domain and two undergo autoprocessing in vitro. In addition, we describe seven Bcl-2-like and two Bak-like proteins. For most of the Bcl-2 family proteins, we have observed mitochondrial localization. When expressed in mammalian cells, HyBak-like 1 and 2 strongly induced apoptosis. Six of the Bcl-2 family members inhibited apoptosis induced by camptothecin in mammalian cells with HyBcl-2-like 4 showing an especially strong protective effect. This protein also interacted with HyBak-like 1 in a yeast two-hybrid assay. Mutation of the conserved leucine in its BH3 domain abolished both the interaction with HyBak-like 1 and the anti-apoptotic effect. Moreover, we describe novel Hydra BH-3-only proteins. One of these interacted with Bcl-2-like 4 and induced apoptosis in mammalian cells. Our data indicate that the evolution of a complex network for cell death regulation arose at the earliest and simplest level of multicellular organization, where it exhibited a substantially higher level of complexity than in the protostome model organisms Caenorhabditis and Drosophila.}, } @article {pmid20479219, year = {2010}, author = {Sebé-Pedrós, A and Roger, AJ and Lang, FB and King, N and Ruiz-Trillo, I}, title = {Ancient origin of the integrin-mediated adhesion and signaling machinery.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {107}, number = {22}, pages = {10142-10147}, pmid = {20479219}, issn = {1091-6490}, support = {206883/ERC_/European Research Council/International ; R01 GM089977/GM/NIGMS NIH HHS/United States ; MOP62809/CAPMC/CIHR/Canada ; }, mesh = {Amino Acid Sequence ; Animals ; CSK Tyrosine-Protein Kinase ; Cell Adhesion/*genetics/*physiology ; Cell Communication/genetics/physiology ; Choanoflagellata/genetics/physiology ; Cyanobacteria/genetics/physiology ; *Evolution, Molecular ; Focal Adhesion Protein-Tyrosine Kinases/genetics ; Fungi/genetics/physiology ; Gene Transfer, Horizontal ; Integrins/chemistry/*genetics/*physiology ; Molecular Sequence Data ; Phylogeny ; Protein-Tyrosine Kinases/genetics ; Sequence Homology, Amino Acid ; Signal Transduction/genetics/physiology ; src-Family Kinases ; }, abstract = {The evolution of animals (metazoans) from their unicellular ancestors required the emergence of novel mechanisms for cell adhesion and cell-cell communication. One of the most important cell adhesion mechanisms for metazoan development is integrin-mediated adhesion and signaling. The integrin adhesion complex mediates critical interactions between cells and the extracellular matrix, modulating several aspects of cell physiology. To date this machinery has been considered strictly metazoan specific. Here we report the results of a comparative genomic analysis of the integrin adhesion machinery, using genomic data from several unicellular relatives of Metazoa and Fungi. Unexpectedly, we found that core components of the integrin adhesion complex are encoded in the genome of the apusozoan protist Amastigomonas sp., and therefore their origins predate the divergence of Opisthokonta, the clade that includes metazoans and fungi. Furthermore, our analyses suggest that key components of this apparatus have been lost independently in fungi and choanoflagellates. Our data highlight the fact that many of the key genes that had formerly been cited as crucial for metazoan origins have a much earlier origin. This underscores the importance of gene cooption in the unicellular-to-multicellular transition that led to the emergence of the Metazoa.}, } @article {pmid20465590, year = {2010}, author = {Kornobis, E and Pálsson, S and Kristjánsson, BK and Svavarsson, J}, title = {Molecular evidence of the survival of subterranean amphipods (Arthropoda) during Ice Age underneath glaciers in Iceland.}, journal = {Molecular ecology}, volume = {19}, number = {12}, pages = {2516-2530}, doi = {10.1111/j.1365-294X.2010.04663.x}, pmid = {20465590}, issn = {1365-294X}, mesh = {Amphipoda/classification/*genetics ; Animals ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; *Genetic Variation ; Geography ; Ice Cover ; Iceland ; Sequence Analysis, DNA ; }, abstract = {A Two endemic groundwater arthropod crustacean species, Crangonyx islandicus and Crymostygius thingvallensis, were recently discovered on the mid-Atlantic volcanic island of Iceland. The extent of morphological differences from closest relatives, endemism, along with the geographic isolation of Iceland and its complete coverage by glaciers 21,000 years ago, suggests that these two species have survived glaciation periods in sub-glacial refugia. Here we provide strong support for this hypothesis by an analysis of mitochondrial genetic variation within Crangonyx islandicus. Our results show that the species is divided into several distinct monophyletic groups that are found along the volcanic zone in Iceland, which have been separated by 0.5 to around 5 million years. The genetic divergence between groups reflects geographic distances between sampling sites, indicating that divergence occurred after the colonization of Iceland. The genetic patterns, as well as the dependency of genetic variation on distances from the tectonic plate boundary and altitude, points to recent expansion from several refugia within Iceland. This presents the first genetic evidence of multicellular organisms as complex as crustacean amphipods which have survived glaciations beneath an ice sheet. This survival may be explained by geothermal heat linked to volcanic activities, which may have maintained favourable habitats in fissures along the tectonic plate boundary in Iceland during glaciations.}, } @article {pmid20460741, year = {2010}, author = {Fushiki, D and Hamada, Y and Yoshimura, R and Endo, Y}, title = {Phylogenetic and bioinformatic analysis of gap junction-related proteins, innexins, pannexins and connexins.}, journal = {Biomedical research (Tokyo, Japan)}, volume = {31}, number = {2}, pages = {133-142}, doi = {10.2220/biomedres.31.133}, pmid = {20460741}, issn = {1880-313X}, mesh = {Amino Acid Sequence ; Animals ; Botany ; Cell Communication/genetics ; Connexins/chemistry/*genetics/metabolism ; Gap Junctions/chemistry/*genetics/*metabolism ; Genome ; Invertebrates/genetics/metabolism ; Research ; Vertebrates/genetics/metabolism ; }, abstract = {All multi-cellular animals, including hydra, insects and vertebrates, develop gap junctions, which communicate directly with neighboring cells. Gap junctions consist of protein families called connexins in vertebrates and innexins in invertebrates. Connexins and innexins have no homology in their amino acid sequence, but both are thought to have some similar characteristics, such as a tetra-membrane-spanning structure, formation of a channel by hexamer, and transmission of small molecules (e.g. ions) to neighboring cells. Pannexins were recently identified as a homolog of innexins in vertebrate genomes. Although pannexins are thought to share the function of intercellular communication with connexins and innexins, there is little information about the relationship among these three protein families of gap junctions. We phylgenetically and bioinformatically examined these protein families and other tetra-membrane-spanning proteins using a database and three analytical softwares. The clades formed by pannexin families do not belong to the species classification but do to paralogs of each member of pannexins. Amino acid sequences of pannexins are closely related to those of innexins but less to those of connexins. These data suggest that innexins and pannexins have a common origin, but the relationship between innexins/pannexins and connexins is as slight as that of other tetra-membrane-spanning members.}, } @article {pmid20459825, year = {2010}, author = {Mazurie, A and Bonchev, D and Schwikowski, B and Buck, GA}, title = {Evolution of metabolic network organization.}, journal = {BMC systems biology}, volume = {4}, number = {}, pages = {59}, pmid = {20459825}, issn = {1752-0509}, support = {R01AI050196/AI/NIAID NIH HHS/United States ; R01AI055347/AI/NIAID NIH HHS/United States ; }, mesh = {Algorithms ; Artificial Intelligence ; Bacteria/metabolism ; Cell Movement ; Computational Biology/methods ; Evolution, Molecular ; Gene Regulatory Networks ; Humans ; Metabolic Networks and Pathways/*genetics ; Models, Biological ; Protein Interaction Mapping ; *Systems Biology ; }, abstract = {BACKGROUND: Comparison of metabolic networks across species is a key to understanding how evolutionary pressures shape these networks. By selecting taxa representative of different lineages or lifestyles and using a comprehensive set of descriptors of the structure and complexity of their metabolic networks, one can highlight both qualitative and quantitative differences in the metabolic organization of species subject to distinct evolutionary paths or environmental constraints.

RESULTS: We used a novel representation of metabolic networks, termed network of interacting pathways or NIP, to focus on the modular, high-level organization of the metabolic capabilities of the cell. Using machine learning techniques we identified the most relevant aspects of cellular organization that change under evolutionary pressures. We considered the transitions from prokarya to eukarya (with a focus on the transitions among the archaea, bacteria and eukarya), from unicellular to multicellular eukarya, from free living to host-associated bacteria, from anaerobic to aerobic, as well as the acquisition of cell motility or growth in an environment of various levels of salinity or temperature. Intuitively, we expect organisms with more complex lifestyles to have more complex and robust metabolic networks. Here we demonstrate for the first time that such organisms are not only characterized by larger, denser networks of metabolic pathways but also have more efficiently organized cross communications, as revealed by subtle changes in network topology. These changes are unevenly distributed among metabolic pathways, with specific categories of pathways being promoted to more central locations as an answer to environmental constraints.

CONCLUSIONS: Combining methods from graph theory and machine learning, we have shown here that evolutionary pressures not only affects gene and protein sequences, but also specific details of the complex wiring of functional modules in the cell. This approach allows the identification and quantification of those changes, and provides an overview of the evolution of intracellular systems.}, } @article {pmid20453877, year = {2010}, author = {Watari, A and Iwabe, N and Masuda, H and Okada, M}, title = {Functional transition of Pak proto-oncogene during early evolution of metazoans.}, journal = {Oncogene}, volume = {29}, number = {26}, pages = {3815-3826}, doi = {10.1038/onc.2010.148}, pmid = {20453877}, issn = {1476-5594}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Humans ; Molecular Sequence Data ; Proto-Oncogene Mas ; *Proto-Oncogenes ; Sequence Homology, Amino Acid ; }, abstract = {Proto-oncogenes encode signaling molecular switches regulating cellular homeostasis in metazoans, and can be converted to oncogenes by gain-of-function mutations. To address the molecular basis for development of the regulatory system of proto-oncogenes during evolution, we screened for ancestral proto-oncogenes from the unicellular choanoflagellate Monosiga ovata by monitoring their transforming activities, and isolated a Pak gene ortholog encoding a serine/threonine kinase as a 'primitive oncogene'. We also cloned Pak orthologs from fungi and the multicellular sponge Ephydatia fluviatilis, and compared their regulatory features with that of M. ovata Pak (MoPak). MoPak is constitutively active and induces cell transformation in mammalian fibroblasts, although the Pak orthologs from multicellular animals are strictly regulated. Analyses of Pak mutants revealed that structural alteration of the auto-inhibitory domain (AID) of MoPak confers higher constitutive kinase activity, as well as greater binding ability to Rho family GTPases than the multicellular Paks, and this structural alteration is responsible for cell transformation and disruption of multicellular tissue organization. These results show that maturation of AID function was required for the development of the strict regulatory system of the Pak proto-oncogene, and suggest a potential link between the establishment of the regulatory system of proto-oncogenes and metazoan evolution.}, } @article {pmid20446452, year = {2010}, author = {Zhang, YQ and Wen, JF}, title = {[MiRNA system in unicellular eukaryotes and its evolutionary implications].}, journal = {Dong wu xue yan jiu = Zoological research}, volume = {31}, number = {1}, pages = {39-42}, doi = {10.3724/sp.j.1141.2010.01039}, pmid = {20446452}, issn = {0254-5853}, mesh = {*Evolution, Molecular ; Giardia/*genetics/metabolism ; MicroRNAs/*genetics/metabolism ; }, abstract = {microRNAs (miRNAs) in higher multicellular eukaryotes have been extensively studied in recent years. Great progresses have also been achieved for miRNAs in unicellular eukaryotes. All these studies not only enrich our knowledge about the complex expression regulation system in diverse organisms, but also have evolutionary significance for understanding the origin of this system. In this review, Authors summarize the recent advance in the studies of miRNA in unicellular eukaryotes, including that on the most primitive unicellular eukaryote--Giardia. The origin and evolution of miRNA system is also discussed.}, } @article {pmid20424833, year = {2010}, author = {Sloan, DB and Taylor, DR}, title = {Testing for selection on synonymous sites in plant mitochondrial DNA: the role of codon bias and RNA editing.}, journal = {Journal of molecular evolution}, volume = {70}, number = {5}, pages = {479-491}, pmid = {20424833}, issn = {1432-1432}, mesh = {Base Composition ; *Codon ; Conserved Sequence ; DNA Fingerprinting ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; *Genome, Mitochondrial ; *Genome, Plant ; Plants/*genetics ; *RNA Editing ; Reproducibility of Results ; Selection, Genetic ; }, abstract = {Since plant mitochondrial genomes exhibit some of the slowest known synonymous substitution rates, it is generally believed that they experience exceptionally low mutation rates. However, the use of synonymous substitution rates to infer mutation rates depends on the implicit assumption that synonymous sites are evolving neutrally (or nearly so). To assess the validity of this assumption in plant mitochondrial genomes, we examined coding sequence for footprints of selection acting at synonymous sites. We found that synonymous sites exhibit an AT rich and pyrimidine skewed nucleotide composition compared to both non-synonymous sites and non-coding regions. We also found some evidence for selection associated with both biased codon usage and conservation of regulatory sequences involved in mRNA processing, although some of these findings are subject to alternative non-adaptive interpretations. Regardless, the inferred strength of selection appears too weak to account for the variation in substitution rates between the mitochondrial genomes of plants and other multicellular eukaryotes. Therefore, these results are consistent with the interpretation that plant mitochondrial genomes experience a substantially lower mutation rate rather than increased functional constraints acting on synonymous sites. Nevertheless, there are important nucleotide composition patterns (particularly the differences between synonymous sites and non-coding DNA) that remain largely unexplained.}, } @article {pmid20421736, year = {2010}, author = {Shaver, S and Casas-Mollano, JA and Cerny, RL and Cerutti, H}, title = {Origin of the polycomb repressive complex 2 and gene silencing by an E(z) homolog in the unicellular alga Chlamydomonas.}, journal = {Epigenetics}, volume = {5}, number = {4}, pages = {301-312}, doi = {10.4161/epi.5.4.11608}, pmid = {20421736}, issn = {1559-2308}, mesh = {Algal Proteins/chemistry/genetics/*metabolism ; Amino Acid Sequence ; Chlamydomonas/*genetics/*metabolism ; Gene Dosage/genetics ; Gene Expression Regulation ; *Gene Silencing ; Histones/metabolism ; Mass Spectrometry ; Molecular Sequence Data ; Phylogeny ; Polycomb-Group Proteins ; Protein Processing, Post-Translational ; Protein Subunits/chemistry/genetics/metabolism ; RNA Interference ; Repressor Proteins/*metabolism ; Retroelements/genetics ; *Sequence Homology, Amino Acid ; Transgenes/genetics ; }, abstract = {Polycomb group proteins play an essential role in the maintenance of cell identity and the regulation of development in both animals and plants. The Polycomb Repressive Complex 2 (PRC2) is involved in the establishment of transcriptionally silent chromatin states, in part through its ability to methylate lysine 27 of histone H3 by the Enhancer of zeste [E(z)] subunit. The absence of PRC2 in unicellular model fungi and its function in the repression of genes vital for the development of higher eukaryotes led to the proposal that this complex may have evolved together with the emergence of multicellularity. However, we report here on the widespread presence of PRC2 core subunits in unicellular eukaryotes from the Opisthokonta, Chromalveolata and Archaeplastida supergroups. To gain insight on the role of PRC2 in single celled organisms, we characterized an E(z) homolog, EZH, in the green alga Chlamydomonas reinhardtii. RNAi-mediated suppression of EZH led to defects in the silencing of transgenes and retrotransposons as well as to a global increase in histone post-translational modifications associated with transcriptional activity, such as trimethylation of histone H3 lysine 4 and acetylation of histone H4. On the basis of the parsimony principle, our findings suggest that PRC2 appeared early in eukaryotic evolution, even perhaps in the last unicellular common ancestor of eukaryotes. One of the ancestral roles of PCR2 may have been in defense responses against intragenomic parasites such as transposable elements, prior to being co-opted for lineage specific functions like developmental regulation in multicellular eukaryotes.}, } @article {pmid20416350, year = {2010}, author = {Sand, SL and Oppegård, C and Ohara, S and Iijima, T and Naderi, S and Blomhoff, HK and Nissen-Meyer, J and Sand, O}, title = {Plantaricin A, a peptide pheromone produced by Lactobacillus plantarum, permeabilizes the cell membrane of both normal and cancerous lymphocytes and neuronal cells.}, journal = {Peptides}, volume = {31}, number = {7}, pages = {1237-1244}, doi = {10.1016/j.peptides.2010.04.010}, pmid = {20416350}, issn = {1873-5169}, mesh = {Animals ; Antineoplastic Agents/metabolism/*pharmacology ; Bacteriocins/biosynthesis/*pharmacology ; Cell Membrane/drug effects/metabolism ; Cell Membrane Permeability/*drug effects ; Flow Cytometry ; Humans ; Jurkat Cells ; Lactobacillus plantarum/*metabolism ; Leukemia/metabolism/pathology ; Lymphocytes/cytology/drug effects/metabolism ; Mice ; Neurons/drug effects/metabolism ; Pheromones/biosynthesis ; Rats ; }, abstract = {Antimicrobial peptides produced by multicellular organisms protect against pathogenic microorganisms, whereas such peptides produced by bacteria provide an ecological advantage over competitors. Certain antimicrobial peptides of metazoan origin are also toxic to eukaryotic cells, with preference for a variety of cancerous cells. Plantaricin A (PlnA) is a peptide pheromone with membrane permeabilizing strain-specific antibacterial activity, produced by Lactobacillus plantarum C11. Recently, we have reported that PlnA also permeabilizes cancerous rat pituitary cells (GH(4) cells), whereas normal rat anterior pituitary cells are resistant. To investigate if preferential effect on cancerous cells is a general feature of PlnA, we have studied effects of the peptide on normal and cancerous lymphocytes and neuronal cells. Normal human B and T cells, Reh cells (from human B cell leukemia), and Jurkat cells (from human T cell leukemia) were studied by flow cytometry to detect morphological changes (scatter) and viability (propidium iodide uptake), and by patch clamp recordings to monitor membrane conductance. Ca(2+) imaging based on a combination of fluo-4 and fura-red was used to monitor PlnA-induced membrane permeabilization in normal rat cortical neurons and glial cells, PC12 cells (from a rat adrenal chromaffin tumor), and murine N2A cells (from a spinal cord tumor). All the tested cell types were affected by 10-100 microM PlnA, whereas concentrations below 10 microM had no significant effect. We conclude that normal and cancerous lymphocytes and neuronal cells show similar sensitivity to PlnA.}, } @article {pmid20398424, year = {2010}, author = {Traylor-Knowles, N and Hansen, U and Dubuc, TQ and Martindale, MQ and Kaufman, L and Finnerty, JR}, title = {The evolutionary diversification of LSF and Grainyhead transcription factors preceded the radiation of basal animal lineages.}, journal = {BMC evolutionary biology}, volume = {10}, number = {}, pages = {101}, pmid = {20398424}, issn = {1471-2148}, support = {R01 GM093116/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA-Binding Proteins/*genetics ; *Evolution, Molecular ; Humans ; Phylogeny ; Transcription Factors/*genetics ; }, abstract = {BACKGROUND: The transcription factors of the LSF/Grainyhead (GRH) family are characterized by the possession of a distinctive DNA-binding domain that bears no clear relationship to other known DNA-binding domains, with the possible exception of the p53 core domain. In triploblastic animals, the LSF and GRH subfamilies have diverged extensively with respect to their biological roles, general expression patterns, and mechanism of DNA binding. For example, Grainyhead (GRH) homologs are expressed primarily in the epidermis, and they appear to play an ancient role in maintaining the epidermal barrier. By contrast, LSF homologs are more widely expressed, and they regulate general cellular functions such as cell cycle progression and survival in addition to cell-lineage specific gene expression.

RESULTS: To illuminate the early evolution of this family and reconstruct the functional divergence of LSF and GRH, we compared homologs from 18 phylogenetically diverse taxa, including four basal animals (Nematostella vectensis, Vallicula multiformis, Trichoplax adhaerens, and Amphimedon queenslandica), a choanoflagellate (Monosiga brevicollis) and several fungi. Phylogenetic and bioinformatic analyses of these sequences indicate that (1) the LSF/GRH gene family originated prior to the animal-fungal divergence, and (2) the functional diversification of the LSF and GRH subfamilies occurred prior to the divergence between sponges and eumetazoans. Aspects of the domain architecture of LSF/GRH proteins are well conserved between fungi, choanoflagellates, and metazoans, though within the Metazoa, the LSF and GRH families are clearly distinct. We failed to identify a convincing LSF/GRH homolog in the sequenced genomes of the algae Volvox carteri and Chlamydomonas reinhardtii or the amoebozoan Dictyostelium purpureum. Interestingly, the ancestral GRH locus has become split into two separate loci in the sea anemone Nematostella, with one locus encoding a DNA binding domain and the other locus encoding the dimerization domain.

CONCLUSIONS: In metazoans, LSF and GRH proteins play a number of roles that are essential to achieving and maintaining multicellularity. It is now clear that this protein family already existed in the unicellular ancestor of animals, choanoflagellates, and fungi. However, the diversification of distinct LSF and GRH subfamilies appears to be a metazoan invention. Given the conserved role of GRH in maintaining epithelial integrity in vertebrates, insects, and nematodes, it is noteworthy that the evolutionary origin of Grh appears roughly coincident with the evolutionary origin of the epithelium.}, } @article {pmid20395508, year = {2010}, author = {Ferris, P and Olson, BJ and De Hoff, PL and Douglass, S and Casero, D and Prochnik, S and Geng, S and Rai, R and Grimwood, J and Schmutz, J and Nishii, I and Hamaji, T and Nozaki, H and Pellegrini, M and Umen, JG}, title = {Evolution of an expanded sex-determining locus in Volvox.}, journal = {Science (New York, N.Y.)}, volume = {328}, number = {5976}, pages = {351-354}, pmid = {20395508}, issn = {1095-9203}, support = {R01 GM078376-02/GM/NIGMS NIH HHS/United States ; T32-HG002536/HG/NHGRI NIH HHS/United States ; T32 HG002536/HG/NHGRI NIH HHS/United States ; R01 GM078376-04/GM/NIGMS NIH HHS/United States ; R01 GM078376-03/GM/NIGMS NIH HHS/United States ; R01 GM078376/GM/NIGMS NIH HHS/United States ; F32 GM086037/GM/NIGMS NIH HHS/United States ; R01 GM078376-01/GM/NIGMS NIH HHS/United States ; R01 GM078376-04S1/GM/NIGMS NIH HHS/United States ; }, mesh = {Algal Proteins/*genetics/metabolism ; Alternative Splicing ; Cell Division ; Chlamydomonas/genetics/physiology ; *Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation ; *Genes ; Genes, Retinoblastoma ; *Genetic Loci ; Introns ; Molecular Sequence Data ; Protozoan Proteins/genetics/metabolism ; Recombination, Genetic ; Reproduction ; Retinoblastoma Protein/genetics/metabolism ; Sequence Analysis, DNA ; Volvox/*genetics/*physiology ; }, abstract = {Although dimorphic sexes have evolved repeatedly in multicellular eukaryotes, their origins are unknown. The mating locus (MT) of the sexually dimorphic multicellular green alga Volvox carteri specifies the production of eggs and sperm and has undergone a remarkable expansion and divergence relative to MT from Chlamydomonas reinhardtii, which is a closely related unicellular species that has equal-sized gametes. Transcriptome analysis revealed a rewired gametic expression program for Volvox MT genes relative to Chlamydomonas and identified multiple gender-specific and sex-regulated transcripts. The retinoblastoma tumor suppressor homolog MAT3 is a Volvox MT gene that displays sexually regulated alternative splicing and evidence of gender-specific selection, both of which are indicative of cooption into the sexual cycle. Thus, sex-determining loci affect the evolution of both sex-related and non-sex-related genes.}, } @article {pmid20394667, year = {2010}, author = {Brown, AJ and Galea, AM}, title = {Cholesterol as an evolutionary response to living with oxygen.}, journal = {Evolution; international journal of organic evolution}, volume = {64}, number = {7}, pages = {2179-2183}, doi = {10.1111/j.1558-5646.2010.01011.x}, pmid = {20394667}, issn = {1558-5646}, mesh = {Adaptation, Biological/*physiology ; *Biological Evolution ; Cataract/metabolism ; Cholesterol/*biosynthesis/*metabolism ; Heart Diseases/metabolism ; Humans ; Neoplasms/metabolism ; Oxygen/*metabolism ; }, abstract = {Although often considered in a negative light, cholesterol is an essential molecule with unusually diverse functions. Cholesterol and related sterols (ergosterol in yeast, phytosterols in plants) is considered a hallmark of eukaryotes, and may even have triggered the evolution of multicellular organisms. Synthesis of cholesterol is an extremely oxygen-intensive process and requires sufficient terrestrial oxygen to proceed. In turn, several lines of evidence support the argument that cholesterol evolved at least in part as an adaptation to the hazards of oxygen. This evolutionary perspective usefully informs medical research on cholesterol to address health-related issues, as illustrated by examples drawn from three prominent human diseases: cataracts, heart disease, and cancer.}, } @article {pmid20393569, year = {2010}, author = {Doroghazi, JR and Buckley, DH}, title = {Widespread homologous recombination within and between Streptomyces species.}, journal = {The ISME journal}, volume = {4}, number = {9}, pages = {1136-1143}, doi = {10.1038/ismej.2010.45}, pmid = {20393569}, issn = {1751-7370}, mesh = {Bacterial Typing Techniques ; DNA Fingerprinting ; DNA, Bacterial/genetics ; Gene Transfer, Horizontal ; Genetic Linkage ; Genotype ; Geography ; *Recombination, Genetic ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; Soil Microbiology ; Streptomyces/*genetics/isolation & purification ; }, abstract = {Horizontal gene transfer (HGT) is widespread in the microbial world, but its impact on the origin and persistence of microbial species remains poorly defined. HGT can result in either acquisition of new genetic material or homologous replacement of existing genes. The evolutionary significance of homologous recombination in a population can be quantified by examining the relative rates at which polymorphisms are introduced from recombination (rho) and mutation (theta(w)). We used multilocus sequence analysis (MLSA) to quantify both intraspecies and interspecies homologous recombination among streptomycetes, multicellular Gram-positive bacteria ubiquitous in soil, which are an important source of antibiotics and bioactive compounds. Intraspecies recombination was examined using strains of Streptomyces flavogriseus isolated from soils at five locations spanning 1000 km. The strains had >99.8% nucleotide identity across the loci examined. We found remarkable levels of gene exchange within S. flavogriseus (rho/theta(w)=27.9), and found that the population was in linkage equilibrium (standardized index of association=0.0018), providing evidence for a freely recombining sexual population structure. We also examined interspecies homologous recombination among different Streptomyces species in an MLSA data set and found that 40% of the species had housekeeping genes acquired through HGT. The recombination rate between these named species (rho/theta(w)=0.21) exceeds that observed within many species of bacteria. Despite widespread gene exchange in the genus, the intraspecies recombination rate exceeded the interspecies rate by two orders of magnitude suggesting that patterns of gene exchange and recombination may shape the evolution of streptomycetes.}, } @article {pmid20388205, year = {2010}, author = {Long, H and Zufall, RA}, title = {Diverse modes of reproduction in the marine free-living ciliate Glauconema trihymene.}, journal = {BMC microbiology}, volume = {10}, number = {}, pages = {108}, pmid = {20388205}, issn = {1471-2180}, mesh = {*Cell Division ; DNA, Protozoan/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Genes, rRNA ; Microscopy ; Molecular Sequence Data ; Oligohymenophorea/classification/cytology/growth & development/*physiology ; RNA, Protozoan/genetics ; RNA, Ribosomal, 18S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Most free-living ciliates reproduce by equal fission or budding during vegetative growth. In certain ciliates, reproduction occurs inside the cyst wall, viz. reproductive cysts, but more complex reproductive strategies have generally been thought to be confined to parasitic or symbiotic species, e.g. Radiophrya spp.

RESULTS: In addition to equal fission, asymmetric binary division and reproductive cysts were discovered in the free-living bacterivorous scuticociliate Glauconema trihymene Thompson, 1966. Asymmetric division is an innate physiological state that can be induced by sufficient food, and the higher the food concentration, the longer the asymmetric division persists. During asymmetric division, nuclear and somatic structures divide with transiently arrested cytokinesis and variable positioning of macronuclei. Phylogenetic analysis, based on the small subunit of ribosomal DNA (SSU rDNA) sequences, showed that the G. trihymene isolate studied here nests with typical scuticociliates and is paraphyletic to both the symbiotic apostome and astome ciliates, some of which also produce progeny by asymmetric division.

CONCLUSIONS: The asymmetric division in G. trihymene has no precedent among undisturbed free-living ciliates. The coexistence of multiple modes of reproduction may represent a previously undescribed reproductive strategy for ciliates living on food patches in coastal waters. This may also be indicative of similar reproductive strategies among other polyphenic ciliates, which have not been intensively studied. Asymmetric division provides a special opportunity for studying ciliates' phenotypic plasticity and may also illuminate the origins of multicellularity.}, } @article {pmid20387382, year = {2010}, author = {Dovgal', IV}, title = {[The evolutionary reorganization of ontogeny and origin of multicellularity].}, journal = {Izvestiia Akademii nauk. Seriia biologicheskaia}, volume = {}, number = {2}, pages = {159-166}, pmid = {20387382}, issn = {1026-3470}, mesh = {*Biological Evolution ; }, abstract = {The formation of morphogenetic mechanisms during emergence of multicellularity is discussed in this article.}, } @article {pmid20383140, year = {2010}, author = {Balestrini, A and Cosentino, C and Errico, A and Garner, E and Costanzo, V}, title = {GEMC1 is a TopBP1-interacting protein required for chromosomal DNA replication.}, journal = {Nature cell biology}, volume = {12}, number = {5}, pages = {484-491}, pmid = {20383140}, issn = {1476-4679}, support = {206281/ERC_/European Research Council/International ; A7124/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Carrier Proteins/genetics/*metabolism/*physiology ; Cell Cycle Proteins/metabolism ; Chromosomes ; Cyclin-Dependent Kinase 2/metabolism ; *DNA Replication ; DNA-Binding Proteins ; Molecular Sequence Data ; Ovum ; Protein Binding ; Replication Origin/genetics ; Xenopus Proteins/metabolism ; Xenopus laevis ; }, abstract = {Many of the factors required for chromosomal DNA replication have been identified in unicellular eukaryotes. However, DNA replication is poorly understood in multicellular organisms. Here, we report the identification of GEMC1 (geminin coiled-coil containing protein 1), a novel vertebrate protein required for chromosomal DNA replication. GEMC1 is highly conserved in vertebrates and is preferentially expressed in proliferating cells. Using Xenopus laevis egg extract we show that Xenopus GEMC1 (xGEMC1) binds to the checkpoint and replication factor TopBP1, which promotes binding of xGEMC1 to chromatin during pre-replication complex (pre-RC) formation. We demonstrate that xGEMC1 interacts directly with replication factors such as Cdc45 and the kinase Cdk2-CyclinE, through which it is heavily phosphorylated. Phosphorylated xGEMC1 stimulates initiation of DNA replication, whereas depletion of xGEMC1 prevents the onset of DNA replication owing to the impairment of Cdc45 loading onto chromatin. Similarly, inhibition of GEMC1 expression with morpholino and siRNA oligos prevents DNA replication in embryonic and somatic vertebrate cells. These data suggest that GEMC1 promotes initiation of chromosomal DNA replication in multicellular organisms by mediating TopBP1- and Cdk2-dependent recruitment of Cdc45 onto replication origins.}, } @article {pmid20381649, year = {2010}, author = {Perry, SF and Spinelli Oliveira, E}, title = {Respiration in a changing environment.}, journal = {Respiratory physiology & neurobiology}, volume = {173 Suppl}, number = {}, pages = {S20-5}, doi = {10.1016/j.resp.2010.04.001}, pmid = {20381649}, issn = {1878-1519}, mesh = {Animals ; Atmosphere/chemistry ; *Biological Evolution ; *Cell Respiration ; *Earth, Planet ; Environment ; Humans ; *Origin of Life ; Oxygen/*metabolism/physiology ; Reactive Oxygen Species/metabolism ; }, abstract = {Multidisciplinary respiratory research highlighted in the present symposium uses existing and new models from all Kingdoms in both basic and applied research and bears upon molecular signaling processes that have been present from the beginning of life and have been maintained as an integral part of it. Many of these old mechanisms are still recognizable as ROS and oxygen-dependent pathways that probably were in place even before photosynthesis evolved. These processes are not only recognizable through relatively small molecules such as nucleotides and their derivatives. Also some DNA sequences such as the hypoxia response elements and pas gene family are ancient and have been co-opted in various functions. The products of pas genes, in addition to their function in regulating nuclear response to hypoxia as part of the hypoxia-inducible factor HIF, play key roles in development, phototransduction, and control of circadian rhythmicity. Also RuBisCO, an enzyme best known for incorporating CO(2) into organic substrates in plants also has an ancient oxygenase function, which plays a key role in regulating peroxide balance in cells. As life forms became more complex and aerobic metabolism became dominant in multicellular organisms, the signaling processes also took on new levels of complexity but many ancient elements remained. The way in which they are integrated into remodeling processes involved in tradeoffs between respiration and nutrition or in control of aging in complex organisms is an exciting field for future research.}, } @article {pmid20376670, year = {2010}, author = {San-José, MC and Corredoira, E and Martínez, MT and Vidal, N and Valladares, S and Mallón, R and Vieitez, AM}, title = {Shoot apex explants for induction of somatic embryogenesis in mature Quercus robur L. trees.}, journal = {Plant cell reports}, volume = {29}, number = {6}, pages = {661-671}, pmid = {20376670}, issn = {1432-203X}, mesh = {Cell Division ; Culture Media ; Embryonic Development ; Plant Growth Regulators/pharmacology ; Plant Shoots/embryology/growth & development ; Quercus/*embryology/growth & development ; Tissue Culture Techniques/*methods ; }, abstract = {A procedure for inducing somatic embryos in shoot apex explants (2 mm) excised from shoot proliferation cultures established from adult oak trees (Quercus robur) was investigated. Embryogenesis was induced in shoot tip as well as leaf explants in three out of the five genotypes evaluated. Somatic embryos were formed by culture in induction medium supplemented with 21.48 muM naphthalene acetic acid and 2.22 muM benzyladenine for 8 weeks, and successive transfer of explants to expression media with a low concentration of growth regulators and without them. Both types of explants formed callus tissue from which somatic embryos developed, indicating indirect embryogenesis. Although the embryogenic frequencies were lower than 12%, it did not prevent the establishment of clonal embryogenic lines maintained by repetitive embryogenesis. Histological study confirmed an indirect somatic embryogenesis process from shoot tip explants, in which leaf primordia and the corresponding axial zones were involved in generating callus, whereas the apical meristem itself did not proliferate. The origin of embryogenic cells appeared to be associated with dedifferentiation of certain parenchymal cells in callus regions after transfer of explants to expression media without auxin. Division of embryogenic cells gave rise to proembryo aggregates of unicellular origin, although a multicellular origin from bulging embryogenic areas would also seem possible. Further development led to the formation of cotyledonary-stage somatic embryos and nodular embryogenic structures that may be considered as anomalous embryos with no clear bipolarity. Inducement of somatic embryos from explants isolated from shoot cultures ensures plant material all year round, thus providing a significant advantage over the use of leaf explants from field-grown trees.}, } @article {pmid20374617, year = {2010}, author = {Feltens, R and Görner, R and Kalkhof, S and Gröger-Arndt, H and von Bergen, M}, title = {Discrimination of different species from the genus Drosophila by intact protein profiling using matrix-assisted laser desorption ionization mass spectrometry.}, journal = {BMC evolutionary biology}, volume = {10}, number = {}, pages = {95}, pmid = {20374617}, issn = {1471-2148}, mesh = {Animals ; Cluster Analysis ; Drosophila/*genetics ; Evolution, Molecular ; Female ; Insect Proteins/genetics ; Male ; *Phylogeny ; Principal Component Analysis ; Proteomics/*methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: The use of molecular biology-based methods for species identification and establishing phylogenetic relationships has supplanted traditional methods relying on morphological characteristics. While PCR-based methods are now the commonly accepted gold standards for these types of analysis, relatively high costs, time-consuming assay development or the need for a priori information about species-specific sequences constitute major limitations. In the present study, we explored the possibility to differentiate between 13 different species from the genus Drosophila via a molecular proteomic approach.

RESULTS: After establishing a simple protein extraction procedure and performing matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) with intact proteins and peptides, we could show that most of the species investigated reproducibly yielded mass spectra that were adequate for species classification. Furthermore, a dendrogram generated by cluster analysis of total protein patterns agrees reasonably well with established phylogenetic relationships.

CONCLUSION: Considering the intra- and interspecies similarities and differences between spectra obtained for specimens of closely related Drosophila species, we estimate that species typing of insects and possibly other multicellular organisms by intact protein profiling (IPP) can be established successfully for species that diverged from a common ancestor about 3 million years ago.}, } @article {pmid20368449, year = {2010}, author = {Schulte, RD and Makus, C and Hasert, B and Michiels, NK and Schulenburg, H}, title = {Multiple reciprocal adaptations and rapid genetic change upon experimental coevolution of an animal host and its microbial parasite.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {107}, number = {16}, pages = {7359-7364}, pmid = {20368449}, issn = {1091-6490}, mesh = {Animals ; Bacillus thuringiensis/*metabolism ; Biological Evolution ; Caenorhabditis elegans/*microbiology ; Genetic Variation ; Genotype ; *Host-Parasite Interactions ; Microsatellite Repeats ; Models, Biological ; Models, Genetic ; Parasites ; Phenotype ; Selection, Genetic ; }, abstract = {The coevolution between hosts and parasites is predicted to have complex evolutionary consequences for both antagonists, often within short time periods. To date, conclusive experimental support for the predictions is available mainly for microbial host systems, but for only a few multicellular host taxa. We here introduce a model system of experimental coevolution that consists of the multicellular nematode host Caenorhabditis elegans and the microbial parasite Bacillus thuringiensis. We demonstrate that 48 host generations of experimental coevolution under controlled laboratory conditions led to multiple changes in both parasite and host. These changes included increases in the traits of direct relevance to the interaction such as parasite virulence (i.e., host killing rate) and host resistance (i.e., the ability to survive pathogens). Importantly, our results provide evidence of reciprocal effects for several other central predictions of the coevolutionary dynamics, including (i) possible adaptation costs (i.e., reductions in traits related to the reproductive rate, measured in the absence of the antagonist), (ii) rapid genetic changes, and (iii) an overall increase in genetic diversity across time. Possible underlying mechanisms for the genetic effects were found to include increased rates of genetic exchange in the parasite and elevated mutation rates in the host. Taken together, our data provide comprehensive experimental evidence of the consequences of host-parasite coevolution, and thus emphasize the pace and complexity of reciprocal adaptations associated with these antagonistic interactions.}, } @article {pmid20368268, year = {2010}, author = {Cocquyt, E and Verbruggen, H and Leliaert, F and De Clerck, O}, title = {Evolution and cytological diversification of the green seaweeds (Ulvophyceae).}, journal = {Molecular biology and evolution}, volume = {27}, number = {9}, pages = {2052-2061}, doi = {10.1093/molbev/msq091}, pmid = {20368268}, issn = {1537-1719}, mesh = {Chlorophyta/classification/*cytology/*genetics ; *Evolution, Molecular ; Phylogeny ; }, abstract = {The Ulvophyceae, one of the four classes of the Chlorophyta, is of particular evolutionary interest because it features an unrivaled morphological and cytological diversity. Morphological types range from unicells and simple multicellular filaments to sheet-like and complex corticated thalli. Cytological layouts range from typical small cells containing a single nucleus and chloroplast to giant cells containing millions of nuclei and chloroplasts. In order to understand the evolution of these morphological and cytological types, the present paper aims to assess whether the Ulvophyceae are monophyletic and elucidate the ancient relationships among its orders. Our approach consists of phylogenetic analyses (maximum likelihood and Bayesian inference) of seven nuclear genes, small subunit nuclear ribosomal DNA and two plastid markers with carefully chosen partitioning strategies, and models of sequence evolution. We introduce a procedure for fast site removal (site stripping) targeted at improving phylogenetic signal in a particular epoch of interest and evaluate the specificity of fast site removal to retain signal about ancient relationships. From our phylogenetic analyses, we conclude that the ancestral ulvophyte likely was a unicellular uninucleate organism and that macroscopic growth was achieved independently in various lineages involving radically different mechanisms: either by evolving multicellularity with coupled mitosis and cytokinesis (Ulvales-Ulotrichales and Trentepohliales), by obtaining a multinucleate siphonocladous organization where every nucleus provides for its own cytoplasmic domain (Cladophorales and Blastophysa), or by developing a siphonous organization characterized by either one macronucleus or millions of small nuclei and cytoplasmic streaming (Bryopsidales and Dasycladales). We compare different evolutionary scenarios giving rise to siphonous and siphonocladous cytologies and argue that these did not necessarily evolve from a multicellular or even multinucleate state but instead could have evolved independently from a unicellular ancestor.}, } @article {pmid20363801, year = {2010}, author = {Lefèvre, CT and Abreu, F and Lins, U and Bazylinski, DA}, title = {Nonmagnetotactic multicellular prokaryotes from low-saline, nonmarine aquatic environments and their unusual negative phototactic behavior.}, journal = {Applied and environmental microbiology}, volume = {76}, number = {10}, pages = {3220-3227}, pmid = {20363801}, issn = {1098-5336}, mesh = {Bacteriological Techniques/methods ; Deltaproteobacteria/classification/genetics/*physiology/ultrastructure ; Geologic Sediments/*microbiology ; *Light ; Magnetics ; Magnetosomes ; Microscopy, Electron, Transmission ; Molecular Sequence Data ; Nevada ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sodium Chloride/analysis ; *Water Microbiology ; }, abstract = {Magnetotactic multicellular prokaryotes (MMPs) are unique magnetotactic bacteria of the Deltaproteobacteria class and the first found to biomineralize the magnetic mineral greigite (Fe(3)S(4)). Thus far they have been reported only from marine habitats. We questioned whether MMPs exist in low-saline, nonmarine environments. MMPs were observed in samples from shallow springs in the Great Boiling Springs geothermal field and Pyramid Lake, both located in northwestern Nevada. The temperature at all sites was ambient, and salinities ranged from 5 to 11 ppt. These MMPs were not magnetotactic and did not contain magnetosomes (called nMMPs here). nMMPs ranged from 7 to 11 microm in diameter, were composed of about 40 to 60 Gram-negative cells, and were motile by numerous flagella that covered each cell on one side, characteristics similar to those of MMPs. 16S rRNA gene sequences of nMMPs show that they form a separate phylogenetic branch within the MMP group in the Deltaproteobacteria class, probably representing a single species. nMMPs exhibited a negative phototactic behavior to white light and to wavelengths of < or =480 nm (blue). We devised a "light racetrack" to exploit this behavior, which was used to photoconcentrate nMMPs for specific purposes (e.g., DNA extraction) even though their numbers were low in the sample. Our results show that the unique morphology of the MMP is not restricted to marine and magnetotactic prokaryotes. Discovery of nonmagnetotactic forms of the MMP might support the hypothesis that acquisition of the magnetosome genes involves horizontal gene transfer. To our knowledge, this is the first report of phototaxis in bacteria of the Deltaproteobacteria class.}, } @article {pmid20363609, year = {2010}, author = {Maric, C and Prioleau, MN}, title = {Interplay between DNA replication and gene expression: a harmonious coexistence.}, journal = {Current opinion in cell biology}, volume = {22}, number = {3}, pages = {277-283}, doi = {10.1016/j.ceb.2010.03.007}, pmid = {20363609}, issn = {1879-0410}, mesh = {Animals ; DNA Replication/*genetics ; *Gene Expression Regulation ; Humans ; Replication Origin/genetics ; Time Factors ; Transcription, Genetic ; }, abstract = {Multicellular organisms have evolved highly sophisticated machinery to that their genomes are accurately duplicated and that the various gene expression programs are established correctly. Recent large-scale studies have shed light on how these fundamental processes interact. Although the machinery mediating these processes share similar cis-regulatory elements, they are not strictly coregulated. Furthermore, studies of the replisome show that highly transcribed genes present a major obstacle to its operation. Further studies will be needed to identify key regulators of the spatio-temporal program of DNA replication, for the elucidation of the complex interplay between replication and transcription.}, } @article {pmid20360212, year = {2010}, author = {Marshall, WL and Berbee, ML}, title = {Population-level analyses indirectly reveal cryptic sex and life history traits of Pseudoperkinsus tapetis (Ichthyosporea, Opisthokonta): a unicellular relative of the animals.}, journal = {Molecular biology and evolution}, volume = {27}, number = {9}, pages = {2014-2026}, doi = {10.1093/molbev/msq078}, pmid = {20360212}, issn = {1537-1719}, mesh = {Animals ; Canada ; Geography ; Haplotypes/genetics ; Invertebrates/parasitology ; Mesomycetozoea/genetics/*growth & development/*physiology ; Polymerase Chain Reaction ; Recombination, Genetic/genetics ; }, abstract = {We use population genetics to detect the molecular footprint of a sexual cycle, of a haploid vegetative state, and of lack of host specificity in Pseudoperkinsus tapetis, a marine unicellular relative of the animals. Prior to this study, complete life cycles were not known for any of the unicellular lineages sharing common ancestry with multicellular animals and fungi. We established the first collection of conspecific cultures of any member from the unicellular opisthokont lineage ichthyosporea, isolating 126 cultures of P. tapetis from guts of marine invertebrates ranging from clams to sea cucumbers. We sequenced fragments of the elongation factor alpha-like (EFL) and heat-shock protein 70 (HSP70) genes for a subset of our isolates. Absence of heterozygotes from the EFL locus in 52 isolates provided evidence for haploidy. Phylogenetic incongruence and a lack of support for linkage between two loci from 34 sequenced isolates signified a history of recombination consistent with a sexual cycle. Shared haplotypes in different invertebrate species showed that P. tapetis was not host specific. Based on estimates of the frequency of sex and on observations of cultures, we propose that P. tapetis is transmitted between hosts via asexual endospores. New protists are continually being discovered, and, as this study illustrates, analysis of culturable collections from natural habitats can transform a species from a near unknown to a model system for better understanding the evolution of life histories.}, } @article {pmid20359467, year = {2010}, author = {Pezzementi, L and Chatonnet, A}, title = {Evolution of cholinesterases in the animal kingdom.}, journal = {Chemico-biological interactions}, volume = {187}, number = {1-3}, pages = {27-33}, doi = {10.1016/j.cbi.2010.03.043}, pmid = {20359467}, issn = {1872-7786}, mesh = {Alternative Splicing/genetics ; Amino Acid Sequence ; Animals ; Biocatalysis ; Cholinesterases/*chemistry/*genetics/metabolism ; *Evolution, Molecular ; Exons/genetics ; Humans ; Mice ; Molecular Sequence Data ; *Phylogeny ; }, abstract = {Cholinesterases emerged from a family of enzymes and proteins with adhesion properties. This family is absent in plants and expanded in multicellular animals. True cholinesterases appeared in triploblastic animals together with the cholinergic system. Lineage specific duplications resulted in two acetylcholinesterases in most hexapods and in up to four genes in nematodes. In vertebrates the duplication leading to acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is now considered to be an ancient event which occurred before the split of osteichthyes. The product of one or the other of the paralogues is responsible for the physiological hydrolysis of acetylcholine, depending on the species lineage and tissue considered. The BChE gene seems to have been lost in some fish lineages. The complete genome of amphioxus (Branchiostoma floridae: cephalochordate) contains a large number of duplicated genes or pseudogenes of cholinesterases. Sequence comparison and tree constructions raise the question of considering the atypical ChE studied in this organism as a representative of ancient BChE. Thus nematodes, arthropods, annelids, molluscs, and vertebrates typically possess two paralogous genes coding for cholinesterases. The origin of the duplication(s) is discussed. The mode of attachment through alternative C-terminal coding exons seems to have evolved independently from the catalytic part of the gene.}, } @article {pmid20359327, year = {2010}, author = {de Mendoza, A and Suga, H and Ruiz-Trillo, I}, title = {Evolution of the MAGUK protein gene family in premetazoan lineages.}, journal = {BMC evolutionary biology}, volume = {10}, number = {}, pages = {93}, pmid = {20359327}, issn = {1471-2148}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Animals ; Eukaryota/*genetics ; *Evolution, Molecular ; Guanylate Kinases/chemistry/*genetics ; Phylogeny ; }, abstract = {BACKGROUND: Cell-to-cell communication is a key process in multicellular organisms. In multicellular animals, scaffolding proteins belonging to the family of membrane-associated guanylate kinases (MAGUK) are involved in the regulation and formation of cell junctions. These MAGUK proteins were believed to be exclusive to Metazoa. However, a MAGUK gene was recently identified in an EST survey of Capsaspora owczarzaki, an unicellular organism that branches off near the metazoan clade. To further investigate the evolutionary history of MAGUK, we have undertook a broader search for this gene family using available genomic sequences of different opisthokont taxa.

RESULTS: Our survey and phylogenetic analyses show that MAGUK proteins are present not only in Metazoa, but also in the choanoflagellate Monosiga brevicollis and in the protist Capsaspora owczarzaki. However, MAGUKs are absent from fungi, amoebozoans or any other eukaryote. The repertoire of MAGUKs in Placozoa and eumetazoan taxa (Cnidaria + Bilateria) is quite similar, except for one class that is missing in Trichoplax, while Porifera have a simpler MAGUK repertoire. However, Vertebrata have undergone several independent duplications and exhibit two exclusive MAGUK classes. Three different MAGUK types are found in both M. brevicollis and C. owczarzaki: DLG, MPP and MAGI. Furthermore, M. brevicollis has suffered a lineage-specific diversification.

CONCLUSIONS: The diversification of the MAGUK protein gene family occurred, most probably, prior to the divergence between Metazoa+choanoflagellates and the Capsaspora+Ministeria clade. A MAGI-like, a DLG-like, and a MPP-like ancestral genes were already present in the unicellular ancestor of Metazoa, and new gene members have been incorporated through metazoan evolution within two major periods, one before the sponge-eumetazoan split and another within the vertebrate lineage. Moreover, choanoflagellates have suffered an independent MAGUK diversification. This study highlights the importance of generating enough genome data from the broadest possible taxonomic sampling, in order to fully understand the evolutionary history of major protein gene families.}, } @article {pmid20348296, year = {2010}, author = {Turroni, F and Foroni, E and O'Connell Motherway, M and Bottacini, F and Giubellini, V and Zomer, A and Ferrarini, A and Delledonne, M and Zhang, Z and van Sinderen, D and Ventura, M}, title = {Characterization of the serpin-encoding gene of Bifidobacterium breve 210B.}, journal = {Applied and environmental microbiology}, volume = {76}, number = {10}, pages = {3206-3219}, pmid = {20348296}, issn = {1098-5336}, mesh = {Amino Acid Sequence ; Base Sequence ; Bifidobacterium/classification/drug effects/*genetics/*metabolism ; Gene Expression Regulation, Bacterial/drug effects ; Genome, Bacterial/genetics ; *Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Sequence Alignment ; Serine Proteases/pharmacology ; Serpins/chemistry/*genetics ; }, abstract = {Members of the serpin (serine protease inhibitor) superfamily have been identified in higher multicellular eukaryotes, as well as in bacteria, although examination of available genome sequences has indicated that homologs of the bacterial serpin-encoding gene (ser) are not widely distributed. In members of the genus Bifidobacterium this gene appears to be present in at least 5, and perhaps up to 9, of the 30 species tested. Moreover, phylogenetic analysis using available bacterial and eukaryotic serpin sequences revealed that bifidobacteria produce serpins that form a separate clade. We characterized the ser(210B) locus of Bifidobacterium breve 210B, which encompasses a number of genes whose deduced protein products display significant similarity to proteins encoded by corresponding loci found in several other bifidobacteria. Northern hybridization, primer extension, microarray, reverse transcription-PCR (RT-PCR), and quantitative real-time PCR (qRT-PCR) analyses revealed that a 3.5-kb polycistronic mRNA encompassing the ser(210B) operon with a single transcriptional start site is strongly induced following treatment of B. breve 210B cultures with some proteases. Interestingly, transcription of other bifidobacterial ser homologs appears to be triggered by different proteases.}, } @article {pmid20308103, year = {2010}, author = {Hughes, KA}, title = {Mutation and the evolution of ageing: from biometrics to system genetics.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {365}, number = {1544}, pages = {1273-1279}, pmid = {20308103}, issn = {1471-2970}, mesh = {Aging/*genetics ; Alleles ; *Evolution, Molecular ; Genetic Fitness ; Genetic Variation ; Humans ; Models, Genetic ; *Mutation ; Quantitative Trait Loci ; Selection, Genetic ; }, abstract = {A notable success for evolutionary genetics during the past century was to generate a coherent, quantitative explanation for an apparent evolutionary paradox: the tendency for multicellular organisms to show declining fitness with age (senescence, often referred to simply as 'ageing'). This general theory is now widely accepted and explains most of the features of senescence that are observed in natural and laboratory populations, but specific instantiations of that theory have been more controversial. To date, most of the empirical tests of these models have relied on data generated from biometric experiments. Modern population genetics and genomics provide new, and probably more powerful, ways to test ideas that are still controversial more than half a century after the original theory was developed. System-genetic experiments have the potential to address both evolutionary and mechanistic questions about ageing by identifying causal loci and the genetic networks with which they interact. Both the biometrical approaches and the newer approaches are reviewed here, with an emphasis on the challenges and limitations that each method faces.}, } @article {pmid20307184, year = {2010}, author = {Grenfell, JL and Rauer, H and Selsis, F and Kaltenegger, L and Beichman, C and Danchi, W and Eiroa, C and Fridlund, M and Henning, T and Herbst, T and Lammer, H and Léger, A and Liseau, R and Lunine, J and Paresce, F and Penny, A and Quirrenbach, A and Röttgering, H and Schneider, J and Stam, D and Tinetti, G and White, GJ}, title = {Co-evolution of atmospheres, life, and climate.}, journal = {Astrobiology}, volume = {10}, number = {1}, pages = {77-88}, doi = {10.1089/ast.2009.0375}, pmid = {20307184}, issn = {1557-8070}, mesh = {Atmosphere/*chemistry ; *Climate ; *Evolution, Planetary ; Oxygen/chemistry ; Ozone/chemistry ; Photosynthesis ; Planets ; *Solar System ; Sunlight ; Ultraviolet Rays ; }, abstract = {After Earth's origin, our host star, the Sun, was shining 20-25% less brightly than today. Without greenhouse-like conditions to warm the atmosphere, our early planet would have been an ice ball, and life may never have evolved. But life did evolve, which indicates that greenhouse gases must have been present on early Earth to warm the planet. Evidence from the geological record indicates an abundance of the greenhouse gas CO(2). CH(4) was probably present as well; and, in this regard, methanogenic bacteria, which belong to a diverse group of anaerobic prokaryotes that ferment CO(2) plus H(2) to CH(4), may have contributed to modification of the early atmosphere. Molecular oxygen was not present, as is indicated by the study of rocks from that era, which contain iron carbonate rather than iron oxide. Multicellular organisms originated as cells within colonies that became increasingly specialized. The development of photosynthesis allowed the Sun's energy to be harvested directly by life-forms. The resultant oxygen accumulated in the atmosphere and formed the ozone layer in the upper atmosphere. Aided by the absorption of harmful UV radiation in the ozone layer, life colonized Earth's surface. Our own planet is a very good example of how life-forms modified the atmosphere over the planets' lifetime. We show that these facts have to be taken into account when we discover and characterize atmospheres of Earth-like exoplanets. If life has originated and evolved on a planet, then it should be expected that a strong co-evolution occurred between life and the atmosphere, the result of which is the planet's climate.}, } @article {pmid20305638, year = {2010}, author = {Kinchen, JM and Ravichandran, KS}, title = {Identification of two evolutionarily conserved genes regulating processing of engulfed apoptotic cells.}, journal = {Nature}, volume = {464}, number = {7289}, pages = {778-782}, pmid = {20305638}, issn = {1476-4687}, support = {R01 GM069998-03/GM/NIGMS NIH HHS/United States ; P30 DK067629/DK/NIDDK NIH HHS/United States ; R01 GM069998-04/GM/NIGMS NIH HHS/United States ; R01 GM069998/GM/NIGMS NIH HHS/United States ; R01 GM064709-06/GM/NIGMS NIH HHS/United States ; R01 GM064709-07/GM/NIGMS NIH HHS/United States ; R01 GM064709/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Apoptosis/*genetics ; Caenorhabditis elegans/cytology/genetics ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Carrier Proteins/genetics/metabolism ; Cell Line ; Conserved Sequence/*genetics ; Disorders of Sex Development ; *Evolution, Molecular ; Gonads/cytology/metabolism ; Guanine Nucleotide Dissociation Inhibitors/metabolism ; Hydrogen-Ion Concentration ; Intracellular Signaling Peptides and Proteins ; Mice ; Multiprotein Complexes/chemistry/metabolism ; NIH 3T3 Cells ; Phagocytosis/*genetics ; Phagosomes/genetics/metabolism ; Protein Binding ; Thymus Gland/cytology ; Two-Hybrid System Techniques ; Vesicular Transport Proteins/genetics/*metabolism ; rab GTP-Binding Proteins/metabolism ; rab5 GTP-Binding Proteins/metabolism ; rab7 GTP-Binding Proteins ; }, abstract = {Engulfment of apoptotic cells occurs throughout life in multicellular organisms. Impaired apoptotic cell clearance (due to defective recognition, internalization or degradation) results in autoimmune disease. One fundamental challenge in understanding how defects in corpse removal translate into diseased states is the identification of critical components orchestrating the different stages of engulfment. Here we use genetic, cell biological and molecular studies in Caenorhabditis elegans and mammalian cells to identify SAND-1 and its partner CCZ-1 as new factors in corpse removal. In worms deficient in either sand-1 or ccz-1, apoptotic cells are internalized and the phagosomes recruit the small GTPase RAB-5 but fail to progress to the subsequent RAB-7(+) stage. The mammalian orthologues of SAND-1, namely Mon1a and Mon1b, were similarly required for phagosome maturation. Mechanistically, Mon1 interacts with GTP-bound Rab5, identifying Mon1 as a previously unrecognized Rab5 effector. Moreover, a Mon1-Ccz1 complex (but not either protein alone) could bind Rab7 and could also influence Rab7 activation, suggesting Mon1-Ccz1 as an important link in progression from the Rab5-positive stage to the Rab7-positive stage of phagosome maturation. Taken together, these data identify SAND-1 (Mon1) and CCZ-1 (Ccz1) as critical and evolutionarily conserved components regulating the processing of ingested apoptotic cell corpses.}, } @article {pmid20303322, year = {2010}, author = {Romeralo, M and Spiegel, FW and Baldauf, SL}, title = {A fully resolved phylogeny of the social amoebas (Dictyostelia) based on combined SSU and ITS rDNA sequences.}, journal = {Protist}, volume = {161}, number = {4}, pages = {539-548}, doi = {10.1016/j.protis.2009.12.006}, pmid = {20303322}, issn = {1618-0941}, mesh = {DNA, Protozoan/genetics ; DNA, Ribosomal/genetics ; DNA, Ribosomal Spacer/genetics ; Dictyosteliida/*classification/genetics ; Phylogeny ; }, abstract = {The dictyostelids possess a complex life cycle including aggregative and multicellular stages. They also include one of the most widely studied protistan model organisms, Dictyostelium discoideum. The current molecular phylogeny of dictyostelids is based largely on SSU (18S) rDNA sequences and shows a deep taxon consisting of four major groups, none of which correspond to the three traditional morphologically-defined genera. However, due to the generally slowly evolving nature of SSU rDNA, these data fail to resolve the majority of branches within the four groups. Given the highly morphologically mixed nature of the dictyostelid groups, it is important to resolve relationships within them. We have determined sequences for the internal transcribed spacers (ITS) of rDNA for nearly all species in the original dictyostelid global phylogeny. Phylogenetic analyses of these data, in combination with the previously determined SSU rDNA sequences, confidently resolve nearly all branches in the tree. This now fully resolved phylogeny confirms the utility of ITS for dictyostelid systematics and lays the ground work for further evolutionary study of the group.}, } @article {pmid20300194, year = {2010}, author = {Conte, D and MacWilliams, HK and Ceccarelli, A}, title = {BTG interacts with retinoblastoma to control cell fate in Dictyostelium.}, journal = {PloS one}, volume = {5}, number = {3}, pages = {e9676}, pmid = {20300194}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Dictyostelium/*metabolism ; Gene Expression Regulation ; Genes, Retinoblastoma ; Models, Biological ; Molecular Sequence Data ; Mutation ; Retinoblastoma Protein/*metabolism ; Sequence Homology, Amino Acid ; Signal Transduction ; }, abstract = {BACKGROUND: In the genesis of many tissues, a phase of cell proliferation is followed by cell cycle exit and terminal differentiation. The latter two processes overlap: genes involved in the cessation of growth may also be important in triggering differentiation. Though conceptually distinct, they are often causally related and functional interactions between the cell cycle machinery and cell fate control networks are fundamental to coordinate growth and differentiation. A switch from proliferation to differentiation may also be important in the life cycle of single-celled organisms, and genes which arose as regulators of microbial differentiation may be conserved in higher organisms. Studies in microorganisms may thus contribute to understanding the molecular links between cell cycle machinery and the determination of cell fate choice networks.

Here we show that in the amoebozoan D. discoideum, an ortholog of the metazoan antiproliferative gene btg controls cell fate, and that this function is dependent on the presence of a second tumor suppressor ortholog, the retinoblastoma-like gene product. Specifically, we find that btg-overexpressing cells preferentially adopt a stalk cell (and, more particularly, an Anterior-Like Cell) fate. No btg-dependent preference for ALC fate is observed in cells in which the retinoblastoma-like gene has been genetically inactivated. Dictyostelium btg is the only example of non-metazoan member of the BTG family characterized so far, suggesting that a genetic interaction between btg and Rb predated the divergence between dictyostelids and metazoa.

CONCLUSIONS/SIGNIFICANCE: While the requirement for retinoblastoma function for BTG antiproliferative activity in metazoans is known, an interaction of these genes in the control of cell fate has not been previously documented. Involvement of a single pathway in the control of mutually exclusive processes may have relevant implication in the evolution of multicellularity.}, } @article {pmid20298777, year = {2010}, author = {Vinogradov, AE}, title = {Human transcriptome nexuses: basic-eukaryotic and metazoan.}, journal = {Genomics}, volume = {95}, number = {6}, pages = {345-354}, doi = {10.1016/j.ygeno.2010.03.004}, pmid = {20298777}, issn = {1089-8646}, mesh = {Animals ; Cell Communication/genetics ; Data Collection ; Databases, Nucleic Acid ; Eukaryota ; *Evolution, Molecular ; *Gene Expression Profiling ; *Gene Regulatory Networks ; Humans ; Nervous System ; }, abstract = {Using a new approach, I analysed human transcriptome coexpression network and revealed two large-scale nexuses. Besides gene coexpression, each nexus is characterized by a combination of gene evolutionary origin, function and among-tissues expression breadth. The first nexus contains mostly genes of pre-metazoan origin, which are widely expressed and have cell-centred functions. The second nexus is enriched in genes of metazoan origin, which are expressed more narrowly and have organism-centred functions. The revealed nexuses are supported by asymmetry in distribution of transcription factor targets between them. Within the metazoan nexus, there is a subnexus that is more pronounced in the nervous tissues and is enriched in gene regulatory complexity. It mostly contains genes related to nervous system, cell communication and multicellular organism processes and development. The revealed nexuses indicate a dichotomy in the transcriptional regulation and can provide a framework for further functional genomics studies.}, } @article {pmid20238418, year = {2010}, author = {Klitgord, N and Segrè, D}, title = {The importance of compartmentalization in metabolic flux models: yeast as an ecosystem of organelles.}, journal = {Genome informatics. International Conference on Genome Informatics}, volume = {22}, number = {}, pages = {41-55}, pmid = {20238418}, issn = {0919-9454}, mesh = {Cell Compartmentation/*physiology ; *Ecosystem ; *Metabolic Networks and Pathways ; *Models, Biological ; Organelles/*metabolism ; Saccharomyces cerevisiae/genetics/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {Understanding the evolution and dynamics of metabolism in microbial ecosystems is an ongoing challenge in microbiology. A promising approach towards this goal is the extension of genome-scale flux balance models of metabolism to multiple interacting species. However, since the detailed distribution of metabolic functions among ecosystem members is often unknown, it is important to investigate how compartmentalization of metabolites and reactions affects flux balance predictions. Here, as a first step in this direction, we address the importance of compartmentalization in the well characterized metabolic model of the yeast Saccharomyces cerevisiae, which we treat as an "ecosystem of organelles". In addition to addressing the impact that the removal of compartmentalization has on model predictions, we show that by systematically constraining some individual fluxes in a de-compartmentalized version of the model we can significantly reduce the flux prediction errors induced by the removal of compartments. We expect that our analysis will help predict and understand metabolic functions in complex microbial communities. In addition, further study of yeast as an ecosystem of organelles might provide novel insight on the evolution of endosymbiosis and multicellularity.}, } @article {pmid20236529, year = {2010}, author = {Parikh, A and Miranda, ER and Katoh-Kurasawa, M and Fuller, D and Rot, G and Zagar, L and Curk, T and Sucgang, R and Chen, R and Zupan, B and Loomis, WF and Kuspa, A and Shaulsky, G}, title = {Conserved developmental transcriptomes in evolutionarily divergent species.}, journal = {Genome biology}, volume = {11}, number = {3}, pages = {R35}, pmid = {20236529}, issn = {1474-760X}, support = {P01 HD039691/HD/NICHD NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; }, mesh = {Base Sequence ; *Biological Evolution ; Conserved Sequence/*genetics ; DNA, Complementary/genetics ; Dictyostelium/cytology/*genetics ; Gene Expression Profiling ; Gene Expression Regulation, Developmental/*genetics ; Gene Regulatory Networks/*genetics ; Molecular Sequence Data ; RNA, Messenger/genetics/*metabolism ; Sequence Analysis, RNA ; Species Specificity ; }, abstract = {BACKGROUND: Evolutionarily divergent organisms often share developmental anatomies despite vast differences between their genome sequences. The social amoebae Dictyostelium discoideum and Dictyostelium purpureum have similar developmental morphologies although their genomes are as divergent as those of man and jawed fish.

RESULTS: Here we show that the anatomical similarities are accompanied by extensive transcriptome conservation. Using RNA sequencing we compared the abundance and developmental regulation of all the transcripts in the two species. In both species, most genes are developmentally regulated and the greatest expression changes occur during the transition from unicellularity to multicellularity. The developmental regulation of transcription is highly conserved between orthologs in the two species. In addition to timing of expression, the level of mRNA production is also conserved between orthologs and is consistent with the intuitive notion that transcript abundance correlates with the amount of protein required. Furthermore, the conservation of transcriptomes extends to cell-type specific expression.

CONCLUSIONS: These findings suggest that developmental programs are remarkably conserved at the transcriptome level, considering the great evolutionary distance between the genomes. Moreover, this transcriptional conservation may be responsible for the similar developmental anatomies of Dictyostelium discoideum and Dictyostelium purpureum.}, } @article {pmid20233411, year = {2010}, author = {Kovalchuk, A and Driessen, AJ}, title = {Phylogenetic analysis of fungal ABC transporters.}, journal = {BMC genomics}, volume = {11}, number = {}, pages = {177}, pmid = {20233411}, issn = {1471-2164}, mesh = {ATP-Binding Cassette Transporters/*genetics ; Algorithms ; DNA, Fungal/genetics ; Evolution, Molecular ; Fungal Proteins/*genetics ; Fungi/*genetics ; *Genome, Fungal ; Multigene Family ; *Phylogeny ; }, abstract = {BACKGROUND: The superfamily of ABC proteins is among the largest known in nature. Its members are mainly, but not exclusively, involved in the transport of a broad range of substrates across biological membranes. Many contribute to multidrug resistance in microbial pathogens and cancer cells. The diversity of ABC proteins in fungi is comparable with those in multicellular animals, but so far fungal ABC proteins have barely been studied.

RESULTS: We performed a phylogenetic analysis of the ABC proteins extracted from the genomes of 27 fungal species from 18 orders representing 5 fungal phyla thereby covering the most important groups. Our analysis demonstrated that some of the subfamilies of ABC proteins remained highly conserved in fungi, while others have undergone a remarkable group-specific diversification. Members of the various fungal phyla also differed significantly in the number of ABC proteins found in their genomes, which is especially reduced in the yeast S. cerevisiae and S. pombe.

CONCLUSIONS: Data obtained during our analysis should contribute to a better understanding of the diversity of the fungal ABC proteins and provide important clues about their possible biological functions.}, } @article {pmid20219261, year = {2010}, author = {Gramzow, L and Ritz, MS and Theissen, G}, title = {On the origin of MADS-domain transcription factors.}, journal = {Trends in genetics : TIG}, volume = {26}, number = {4}, pages = {149-153}, doi = {10.1016/j.tig.2010.01.004}, pmid = {20219261}, issn = {0168-9525}, mesh = {Animals ; Antigens, Neoplasm/genetics/metabolism ; DNA Topoisomerases, Type II/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Eukaryota/*genetics ; Gene Duplication ; MADS Domain Proteins/chemistry/*genetics/metabolism ; }, abstract = {MADS-domain transcription factors are involved in signal transduction and developmental control in plants, animals and fungi. Because their diversification is linked to the origin of novelties in multicellular eukaryotes, the early evolution of MADS-domain proteins is of interest, but has remained enigmatic. Employing whole genome sequence information and remote homology detection methods, we demonstrate that the MADS domain originated from a region of topoisomerases IIA subunit A. Furthermore, we provide evidence that gene duplication occurred in the lineage that led to the MRCA of extant eukaryotes, giving rise to SRF-like and MEF2-like MADS-box genes.}, } @article {pmid20219099, year = {2010}, author = {Zachar, I and Szathmáry, E}, title = {A new replicator: a theoretical framework for analysing replication.}, journal = {BMC biology}, volume = {8}, number = {}, pages = {21}, pmid = {20219099}, issn = {1741-7007}, mesh = {DNA Replication ; Evolution, Molecular ; *Models, Genetic ; }, abstract = {BACKGROUND: Replicators are the crucial entities in evolution. The notion of a replicator, however, is far less exact than the weight of its importance. Without identifying and classifying multiplying entities exactly, their dynamics cannot be determined appropriately. Therefore, it is importance to decide the nature and characteristics of any multiplying entity, in a detailed and formal way.

RESULTS: Replication is basically an autocatalytic process which enables us to rest on the notions of formal chemistry. This statement has major implications. Simple autocatalytic cycle intermediates are considered as non-informational replicators. A consequence of which is that any autocatalytically multiplying entity is a replicator, be it simple or overly complex (even nests). A stricter definition refers to entities which can inherit acquired changes (informational replicators). Simple autocatalytic molecules (and nests) are excluded from this group. However, in turn, any entity possessing copiable information is to be named a replicator, even multicellular organisms. In order to deal with the situation, an abstract, formal framework is presented, which allows the proper identification of various types of replicators. This sheds light on the old problem of the units and levels of selection and evolution. A hierarchical classification for the partition of the replicator-continuum is provided where specific replicators are nested within more general ones. The classification should be able to be successfully applied to known replicators and also to future candidates.

CONCLUSION: This paper redefines the concept of the replicator from a bottom-up theoretical approach. The formal definition and the abstract models presented can distinguish between among all possible replicator types, based on their quantity of variable and heritable information. This allows for the exact identification of various replicator types and their underlying dynamics. The most important claim is that replication, in general, is basically autocatalysis, with a specific defined environment and selective force. A replicator is not valid unless its working environment, and the selective force to which it is subject, is specified.}, } @article {pmid20214803, year = {2010}, author = {Brameier, M}, title = {Genome-wide comparative analysis of microRNAs in three non-human primates.}, journal = {BMC research notes}, volume = {3}, number = {}, pages = {64}, pmid = {20214803}, issn = {1756-0500}, abstract = {BACKGROUND: MicroRNAs (miRNAs) are negative regulators of gene expression in multicellular eukaryotes. With the recently completed sequencing of three primate genomes, the study of miRNA evolution within the primate lineage has only begun and may be expected to provide the genetic and molecular explanations for many phenotypic differences between human and non-human primates.

FINDINGS: We scanned all three genomes of non-human primates, including chimpanzee (Pan troglodytes), orangutan (Pongo pygmaeus), and rhesus monkey (Macaca mulatta), for homologs of human miRNA genes. Besides sequence homology analysis, our comparative method relies on various postprocessing filters to verify other features of miRNAs, including, in particular, their precursor structure or their occurrence (prediction) in other primate genomes. Our study allows direct comparisons between the different species in terms of their miRNA repertoire, their evolutionary distance to human, the effects of filters, as well as the identification of common and species-specific miRNAs in the primate lineage. More than 500 novel putative miRNA genes have been discovered in orangutan that show at least 85 percent identity in precursor sequence. Only about 40 percent are found to be 100 percent identical with their human ortholog.

CONCLUSION: Homologs of human precursor miRNAs with perfect or near-perfect sequence identity may be considered to be likely functional in other primates. The computational identification of homologs with less similar sequence, instead, requires further evidence to be provided.}, } @article {pmid20212005, year = {2010}, author = {Singh, RS and Artieri, CG}, title = {Male sex drive and the maintenance of sex: evidence from Drosophila.}, journal = {The Journal of heredity}, volume = {101 Suppl 1}, number = {}, pages = {S100-6}, doi = {10.1093/jhered/esq006}, pmid = {20212005}, issn = {1465-7333}, mesh = {Animals ; *Biological Evolution ; Drosophila/*physiology ; Genetic Fitness/genetics ; Genetic Variation ; Genomics/methods ; Male ; Mating Preference, Animal/*physiology ; Models, Genetic ; Reproduction/genetics/*physiology ; Selection, Genetic/*genetics ; *Sex ; }, abstract = {The resolution of the paradoxes surrounding the evolutionary origins and maintenance of sexual reproduction has been a major focus in biology. The operation of sexual selection-which is very common among multicellular organisms-has been proposed as an important factor in the maintenance of sex, though in order for this hypothesis to hold, the strength of sexual selection must be stronger in males than in females. Sexual selection poses its own series of evolutionary questions, including how genetic variability is maintained in the face of sustained directional selection (known as the "paradox of the lek"). In this short review, we present evidence obtained from recent comparative genomics projects arguing that 1) the genomic consequences of sexual selection clearly show that its effect is stronger in males and 2) this sustained selection over evolutionary timescales also has an effect of capturing de novo genes and expression patterns influencing male fitness, thus providing a mechanism via which new genetic variation can be input into to male traits. Furthermore, we argue that this latter process of genomic "masculinization" has an additional effect of making males difficult to purge from populations, as evidence from Drosophila indicates that, for example, many male sexually selected seminal fluid factors are required to ensure maximally efficient reproduction. Newly arising parthenogenic mutations would suffer an immediate reproductive rate disadvantage were these proteins lost. We show that recent studies confirm that genomic masculinization, as a result of "male sex drive," has important consequences for the evolution of sexually dimorphic species.}, } @article {pmid20207153, year = {2010}, author = {de Albuquerque, JP and Keim, CN and Lins, U}, title = {Comparative analysis of Beggiatoa from hypersaline and marine environments.}, journal = {Micron (Oxford, England : 1993)}, volume = {41}, number = {5}, pages = {507-517}, doi = {10.1016/j.micron.2010.01.009}, pmid = {20207153}, issn = {1878-4291}, mesh = {Beggiatoa/classification/*cytology/genetics/*isolation & purification ; Cluster Analysis ; Cytoplasm/ultrastructure ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Inclusion Bodies/chemistry ; Locomotion ; Microscopy ; Microscopy, Electron, Transmission ; Molecular Sequence Data ; Nitrates/analysis ; Periplasm/chemistry ; Phosphorus/analysis ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sulfur/analysis ; Vacuoles/ultrastructure ; *Water Microbiology ; }, abstract = {The main criterion to classify a microorganism as belonging to the genus Beggiatoa is its morphology. All multicellular, colorless, gliding bacterial filaments containing sulfur globules described so far belong to this genus. At the ultrastructural level, they show also a very complex cell envelope structure. Here we describe uncultured vacuolated and non-vacuolated bacteria from two different environments showing all characteristics necessary to assign a bacterium to the genus Beggiatoa. We also intended to investigate whether narrow and vacuolate Beggiatoa do differ morphologically as much as they do phylogenetically. Both large, vacuolated trichomes and narrow filaments devoid of vacuoles were observed. We confirmed the identity of the narrow filaments by 16S rRNA phylogenetic analysis. The diameters of the trichomes ranged from 2.4 to 34 microm, and their lengths ranged from 10 microm to over 30 mm. Narrow trichomes moved by gliding at 3.0 microm/s; large filaments moved at 1.5 microm/s. Periplasmic sulfur inclusions were observed in both types of filaments, whereas phosphorus-rich bodies were found only in narrow trichomes. On the other hand, nitrate vacuoles were observed only in large trichomes. Ultra-thin section transmission electron microscopy showed differences between the cell ultrastructure of narrow (non-vacuolated) and large (vacuolated) Beggiatoa. We observed that cell envelopes from narrow Beggiatoa consist of five layers, whereas cell envelopes from large trichomes contain four layers.}, } @article {pmid20206280, year = {2010}, author = {Schachter, H}, title = {Mgat1-dependent N-glycans are essential for the normal development of both vertebrate and invertebrate metazoans.}, journal = {Seminars in cell & developmental biology}, volume = {21}, number = {6}, pages = {609-615}, doi = {10.1016/j.semcdb.2010.02.010}, pmid = {20206280}, issn = {1096-3634}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Acyltransferases/genetics/*metabolism ; Animals ; Caenorhabditis elegans/genetics/*metabolism ; Carbohydrate Conformation ; Carbohydrate Sequence ; Drosophila melanogaster/genetics/*metabolism ; Humans ; Mice ; Molecular Sequence Data ; Morphogenesis/*physiology ; *Mutation ; N-Acetylglucosaminyltransferases ; Phosphorylcholine/metabolism ; Polysaccharides/chemistry/*metabolism ; }, abstract = {UDP-GlcNAc:alpha3-D-mannoside beta1,2-N-acetylglucosaminyltransferase I (GnTI, encoded by Mgat1) first appeared in evolution at about the same time as metazoa suggesting that GnTI-dependent glycans are essential for the development of multicellular organisms. This review describes the effects of mutations in the Mgat1 gene on the development of Caenorhabditis elegans, Drosophila melanogaster and mice.}, } @article {pmid20195512, year = {2010}, author = {Grönke, S and Clarke, DF and Broughton, S and Andrews, TD and Partridge, L}, title = {Molecular evolution and functional characterization of Drosophila insulin-like peptides.}, journal = {PLoS genetics}, volume = {6}, number = {2}, pages = {e1000857}, pmid = {20195512}, issn = {1553-7404}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Body Weight/drug effects ; Diet ; Drosophila/drug effects/*genetics/growth & development/microbiology ; Drosophila Proteins/*genetics/*metabolism ; Drug Resistance/drug effects ; Energy Metabolism/drug effects/genetics ; *Evolution, Molecular ; Fertility/drug effects ; Gene Expression Regulation, Developmental/drug effects ; Genetic Loci/genetics ; Longevity/drug effects ; Mutation/genetics ; Ovum/cytology/drug effects ; Phylogeny ; Stress, Physiological/drug effects/genetics ; Survival Analysis ; Time Factors ; Wolbachia/metabolism ; Xenobiotics/pharmacology ; }, abstract = {Multicellular animals match costly activities, such as growth and reproduction, to the environment through nutrient-sensing pathways. The insulin/IGF signaling (IIS) pathway plays key roles in growth, metabolism, stress resistance, reproduction, and longevity in diverse organisms including mammals. Invertebrate genomes often contain multiple genes encoding insulin-like ligands, including seven Drosophila insulin-like peptides (DILPs). We investigated the evolution, diversification, redundancy, and functions of the DILPs, combining evolutionary analysis, based on the completed genome sequences of 12 Drosophila species, and functional analysis, based on newly-generated knock-out mutations for all 7 dilp genes in D. melanogaster. Diversification of the 7 DILPs preceded diversification of Drosophila species, with stable gene diversification and family membership, suggesting stabilising selection for gene function. Gene knock-outs demonstrated both synergy and compensation of expression between different DILPs, notably with DILP3 required for normal expression of DILPs 2 and 5 in brain neurosecretory cells and expression of DILP6 in the fat body compensating for loss of brain DILPs. Loss of DILP2 increased lifespan and loss of DILP6 reduced growth, while loss of DILP7 did not affect fertility, contrary to its proposed role as a Drosophila relaxin. Importantly, loss of DILPs produced in the brain greatly extended lifespan but only in the presence of the endosymbiontic bacterium Wolbachia, demonstrating a specific interaction between IIS and Wolbachia in lifespan regulation. Furthermore, loss of brain DILPs blocked the responses of lifespan and fecundity to dietary restriction (DR) and the DR response of these mutants suggests that IIS extends lifespan through mechanisms that both overlap with those of DR and through additional mechanisms that are independent of those at work in DR. Evolutionary conservation has thus been accompanied by synergy, redundancy, and functional differentiation between DILPs, and these features may themselves be of evolutionary advantage.}, } @article {pmid20190021, year = {2011}, author = {Filippini, M and Svercel, M and Laczko, E and Kaech, A and Ziegler, U and Bagheri, HC}, title = {Fibrella aestuarina gen. nov., sp. nov., a filamentous bacterium of the family Cytophagaceae isolated from a tidal flat, and emended description of the genus Rudanella Weon et al. 2008.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {61}, number = {Pt 1}, pages = {184-189}, doi = {10.1099/ijs.0.020503-0}, pmid = {20190021}, issn = {1466-5034}, mesh = {Base Composition ; Cluster Analysis ; Cytophagaceae/*classification/genetics/*isolation & purification/physiology ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Fatty Acids/analysis ; *Geologic Sediments ; Germany ; Hydrogen-Ion Concentration ; Molecular Sequence Data ; North Sea ; Phospholipids/analysis ; Phylogeny ; Quinones/analysis ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sodium Chloride/metabolism ; *Soil Microbiology ; Temperature ; }, abstract = {A Gram-staining-negative, pink bacterium, designated strain BUZ 2(T), was isolated from coastal mud from the North Sea (Fedderwardersiel, Germany). Cells were rod-shaped and able to form multicellular filaments. Growth after 7 days was observed at 10-40 °C, at pH 6-8 and with 0-0.5 % NaCl. The phylogenetic tree based on 16S rRNA gene sequences indicated that strain BUZ 2(T) is a member of the family Cytophagaceae, its closest neighbours being Rudanella lutea 5715S-11(T), Spirosoma linguale LMG 10896(T) and Spirosoma panaciterrae Gsoil 1519(T) (87.8, 86.4 and 86.1 % sequence similarity, respectively). The major fatty acids were summed feature 3 (comprising C(16 : 1)ω7c and/or iso-C(15 : 0) 2-OH), C(16 : 1)ω5c and iso-C(15 : 0). The predominant respiratory quinone was MK-7 and the major polar lipids were phosphatidylethanolamine and several unidentified aminophospholipids. The DNA G+C content was 56.5 mol%. On the basis of this polyphasic study, we propose that strain BUZ 2(T) represents a novel genus and species, for which the name Fibrella aestuarina gen. nov., sp. nov. is proposed. The type strain of Fibrella aestuarina is BUZ 2(T) (=DSM 22563(T) =CCUG 58136(T)). An emended description of the genus Rudanella is also proposed.}, } @article {pmid20186335, year = {2010}, author = {Shina, MC and Müller, R and Blau-Wasser, R and Glöckner, G and Schleicher, M and Eichinger, L and Noegel, AA and Kolanus, W}, title = {A cytohesin homolog in Dictyostelium amoebae.}, journal = {PloS one}, volume = {5}, number = {2}, pages = {e9378}, pmid = {20186335}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Amoeba/*genetics/metabolism/physiology ; Animals ; Cell Adhesion Molecules/*genetics/metabolism ; Chemotaxis/physiology ; Cyclic AMP/metabolism ; Dictyostelium/*genetics/metabolism/physiology ; Genome, Protozoan/genetics ; Green Fluorescent Proteins/genetics/metabolism ; Guanine Nucleotide Exchange Factors/classification/genetics/metabolism ; Microscopy, Fluorescence ; Molecular Sequence Data ; Movement/physiology ; *Mutation ; Phylogeny ; Protein Isoforms/classification/genetics/metabolism ; Protozoan Proteins/classification/*genetics/metabolism ; Sequence Homology, Amino Acid ; }, abstract = {BACKGROUND: Dictyostelium, an amoeboid motile cell, harbors several paralogous Sec7 genes that encode members of three distinct subfamilies of the Sec7 superfamily of Guanine nucleotide exchange factors. Among them are proteins of the GBF/BIG family present in all eukaryotes. The third subfamily represented with three members in D. discoideum is the cytohesin family that has been thought to be metazoan specific. Cytohesins are characterized by a Sec7 PH tandem domain and have roles in cell adhesion and migration.

PRINCIPAL FINDINGS: Dictyostelium SecG exhibits highest homologies to the cytohesins. It harbors at its amino terminus several ankyrin repeats that are followed by the Sec7 PH tandem domain. Mutants lacking SecG show reduced cell-substratum adhesion whereas cell-cell adhesion that is important for development is not affected. Accordingly, multicellular development proceeds normally in the mutant. During chemotaxis secG(-) cells elongate and migrate in a directed fashion towards cAMP, however speed is moderately reduced.

SIGNIFICANCE: The data indicate that SecG is a relevant factor for cell-substrate adhesion and reveal the basic function of a cytohesin in a lower eukaryote.}, } @article {pmid20185755, year = {2010}, author = {Tachibana, K and Mori, M and Matsuhira, T and Karino, T and Inagaki, T and Nagayama, A and Nishiyama, A and Hara, M and Kishimoto, T}, title = {Initiation of DNA replication after fertilization is regulated by p90Rsk at pre-RC/pre-IC transition in starfish eggs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {107}, number = {11}, pages = {5006-5011}, pmid = {20185755}, issn = {1091-6490}, mesh = {Animals ; Cell Cycle Proteins/metabolism ; Chromatin/metabolism ; Cyclin-Dependent Kinases/metabolism ; *DNA Replication ; Enzyme Activation ; Female ; Fertilization/*physiology ; G1 Phase ; Meiosis ; Molecular Sequence Data ; Ovum/cytology/*enzymology ; Replication Origin ; Ribosomal Protein S6 Kinases, 90-kDa/*metabolism ; Starfish/*cytology/*enzymology ; }, abstract = {Initiation of DNA replication in eukaryotic cells is controlled through an ordered assembly of protein complexes at replication origins. The molecules involved in this process are well conserved but diversely regulated. Typically, initiation of DNA replication is regulated in response to developmental events in multicellular organisms. Here, we elucidate the regulation of the first S phase of the embryonic cell cycle after fertilization. Unless fertilization occurs, the Mos-MAPK-p90Rsk pathway causes the G1-phase arrest after completion of meiosis in starfish eggs. Fertilization shuts down this pathway, leading to the first S phase with no requirement of new protein synthesis. However, how and in which stage the initiation complex for DNA replication is arrested by p90Rsk remains unclear. We find that in G1-arrested eggs, chromatin is loaded with the Mcm complex to form the prereplicative complex (pre-RC). Inactivation of p90Rsk is necessary and sufficient for further loading of Cdc45 onto chromatin to form the preinitiation complex (pre-IC) and the subsequent initiation of DNA replication. However, cyclin A-, B-, and E-Cdk's activity and Cdc7 accumulation are dispensable for these processes. These observations define the stage of G1 arrest in unfertilized eggs at transition point from pre-RC to pre-IC, and reveal a unique role of p90Rsk for a negative regulator of this transition. Thus, initiation of DNA replication in the meiosis-to-mitosis transition is regulated at the pre-RC stage as like in the G1 checkpoint, but in a manner different from the checkpoint.}, } @article {pmid20169397, year = {2010}, author = {Schrader, K and Huai, J and Jöckel, L and Oberle, C and Borner, C}, title = {Non-caspase proteases: triggers or amplifiers of apoptosis?.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {67}, number = {10}, pages = {1607-1618}, pmid = {20169397}, issn = {1420-9071}, mesh = {Animals ; *Apoptosis ; Caspases/*metabolism ; Humans ; Lysosomes/enzymology ; }, abstract = {Caspases are the most important effectors of apoptosis, the major form of programmed cell death (PCD) in multicellular organisms. This is best reflected by the appearance of serious development defects in mice deficient for caspase-8, -9, and -3. Meanwhile, caspase-independent PCD, mediated by other proteases or signaling components has been described in numerous publications. Although we do not doubt that such cell death exists, we propose that it has evolved later during evolution and is most likely not designed to execute, but to amplify and speed-up caspase-dependent cell death. This review shall provide evidence for such a concept.}, } @article {pmid20169188, year = {2010}, author = {Mair, GR and Lasonder, E and Garver, LS and Franke-Fayard, BM and Carret, CK and Wiegant, JC and Dirks, RW and Dimopoulos, G and Janse, CJ and Waters, AP}, title = {Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development.}, journal = {PLoS pathogens}, volume = {6}, number = {2}, pages = {e1000767}, pmid = {20169188}, issn = {1553-7374}, support = {/WT_/Wellcome Trust/United Kingdom ; 083811/WT_/Wellcome Trust/United Kingdom ; R01 AI061576/AI/NIAID NIH HHS/United States ; 1R01AI061576-01A1/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Blotting, Southern ; Blotting, Western ; Female ; Flow Cytometry ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation/*physiology ; Germ Cells ; Immunoprecipitation ; Phylogeny ; Plasmodium berghei/*physiology ; Protozoan Proteins/*physiology ; RNA Interference/*physiology ; RNA, Messenger/genetics ; Ribonucleoproteins/physiology ; Sexual Development ; Zygote ; }, abstract = {A universal feature of metazoan sexual development is the generation of oocyte P granules that withhold certain mRNA species from translation to provide coding potential for proteins during early post-fertilization development. Stabilisation of translationally quiescent mRNA pools in female Plasmodium gametocytes depends on the RNA helicase DOZI, but the molecular machinery involved in the silencing of transcripts in these protozoans is unknown. Using affinity purification coupled with mass-spectrometric analysis we identify a messenger ribonucleoprotein (mRNP) from Plasmodium berghei gametocytes defined by DOZI and the Sm-like factor CITH (homolog of worm CAR-I and fly Trailer Hitch). This mRNP includes 16 major factors, including proteins with homologies to components of metazoan P granules and archaeal proteins. Containing translationally silent transcripts, this mRNP integrates eIF4E and poly(A)-binding protein but excludes P body RNA degradation factors and translation-initiation promoting eIF4G. Gene deletion mutants of 2 core components of this mRNP (DOZI and CITH) are fertilization-competent, but zygotes fail to develop into ookinetes in a female gametocyte-mutant fashion. Through RNA-immunoprecipitation and global expression profiling of CITH-KO mutants we highlight CITH as a crucial repressor of maternally supplied mRNAs. Our data define Plasmodium P granules as an ancient mRNP whose protein core has remained evolutionarily conserved from single-cell organisms to germ cells of multi-cellular animals and stores translationally silent mRNAs that are critical for early post-fertilization development during the initial stages of mosquito infection. Therefore, translational repression may offer avenues as a target for the generation of transmission blocking strategies and contribute to limiting the spread of malaria.}, } @article {pmid20169071, year = {2010}, author = {Stucken, K and John, U and Cembella, A and Murillo, AA and Soto-Liebe, K and Fuentes-Valdés, JJ and Friedel, M and Plominsky, AM and Vásquez, M and Glöckner, G}, title = {The smallest known genomes of multicellular and toxic cyanobacteria: comparison, minimal gene sets for linked traits and the evolutionary implications.}, journal = {PloS one}, volume = {5}, number = {2}, pages = {e9235}, pmid = {20169071}, issn = {1932-6203}, mesh = {Bacterial Proteins/*genetics ; Bacterial Toxins/metabolism ; Cyanobacteria/classification/*genetics/metabolism ; Cylindrospermopsis/cytology/*genetics/ultrastructure ; Evolution, Molecular ; Genome, Bacterial/*genetics ; Microscopy, Electron, Transmission ; Multigene Family/genetics ; Nitrogen Fixation/genetics ; Phylogeny ; Repetitive Sequences, Nucleic Acid/genetics ; Sequence Analysis, DNA ; Species Specificity ; Synteny ; }, abstract = {Cyanobacterial morphology is diverse, ranging from unicellular spheres or rods to multicellular structures such as colonies and filaments. Multicellular species represent an evolutionary strategy to differentiate and compartmentalize certain metabolic functions for reproduction and nitrogen (N(2)) fixation into specialized cell types (e.g. akinetes, heterocysts and diazocytes). Only a few filamentous, differentiated cyanobacterial species, with genome sizes over 5 Mb, have been sequenced. We sequenced the genomes of two strains of closely related filamentous cyanobacterial species to yield further insights into the molecular basis of the traits of N(2) fixation, filament formation and cell differentiation. Cylindrospermopsis raciborskii CS-505 is a cylindrospermopsin-producing strain from Australia, whereas Raphidiopsis brookii D9 from Brazil synthesizes neurotoxins associated with paralytic shellfish poisoning (PSP). Despite their different morphology, toxin composition and disjunct geographical distribution, these strains form a monophyletic group. With genome sizes of approximately 3.9 (CS-505) and 3.2 (D9) Mb, these are the smallest genomes described for free-living filamentous cyanobacteria. We observed remarkable gene order conservation (synteny) between these genomes despite the difference in repetitive element content, which accounts for most of the genome size difference between them. We show here that the strains share a specific set of 2539 genes with >90% average nucleotide identity. The fact that the CS-505 and D9 genomes are small and streamlined compared to those of other filamentous cyanobacterial species and the lack of the ability for heterocyst formation in strain D9 allowed us to define a core set of genes responsible for each trait in filamentous species. We presume that in strain D9 the ability to form proper heterocysts was secondarily lost together with N(2) fixation capacity. Further comparisons to all available cyanobacterial genomes covering almost the entire evolutionary branch revealed a common minimal gene set for each of these cyanobacterial traits.}, } @article {pmid20163699, year = {2010}, author = {Lin, CF and Mount, SM and Jarmołowski, A and Makałowski, W}, title = {Evolutionary dynamics of U12-type spliceosomal introns.}, journal = {BMC evolutionary biology}, volume = {10}, number = {}, pages = {47}, pmid = {20163699}, issn = {1471-2148}, mesh = {Animals ; Arabidopsis/genetics ; Evolution, Molecular ; Humans ; Introns ; RNA, Small Nuclear/*genetics ; Spliceosomes/*genetics ; }, abstract = {BACKGROUND: Many multicellular eukaryotes have two types of spliceosomes for the removal of introns from messenger RNA precursors. The major (U2) spliceosome processes the vast majority of introns, referred to as U2-type introns, while the minor (U12) spliceosome removes a small fraction (less than 0.5%) of introns, referred to as U12-type introns. U12-type introns have distinct sequence elements and usually occur together in genes with U2-type introns. A phylogenetic distribution of U12-type introns shows that the minor splicing pathway appeared very early in eukaryotic evolution and has been lost repeatedly.

RESULTS: We have investigated the evolution of U12-type introns among eighteen metazoan genomes by analyzing orthologous U12-type intron clusters. Examination of gain, loss, and type switching shows that intron type is remarkably conserved among vertebrates. Among 180 intron clusters, only eight show intron loss in any vertebrate species and only five show conversion between the U12 and the U2-type. Although there are only nineteen U12-type introns in Drosophila melanogaster, we found one case of U2 to U12-type conversion, apparently mediated by the activation of cryptic U12 splice sites early in the dipteran lineage. Overall, loss of U12-type introns is more common than conversion to U2-type and the U12 to U2 conversion occurs more frequently among introns of the GT-AG subtype than among introns of the AT-AC subtype. We also found support for natural U12-type introns with non-canonical terminal dinucleotides (CT-AC, GG-AG, and GA-AG) that have not been previously reported.

CONCLUSIONS: Although complete loss of the U12-type spliceosome has occurred repeatedly, U12 introns are extremely stable in some taxa, including eutheria. Loss of U12 introns or the genes containing them is more common than conversion to the U2-type. The degeneracy of U12-type terminal dinucleotides among natural U12-type introns is higher than previously thought.}, } @article {pmid20160088, year = {2010}, author = {Ozbudak, EM and Tassy, O and Pourquié, O}, title = {Spatiotemporal compartmentalization of key physiological processes during muscle precursor differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {107}, number = {9}, pages = {4224-4229}, pmid = {20160088}, issn = {1091-6490}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Cell Cycle ; *Cell Differentiation ; DNA/metabolism ; Gene Expression Profiling ; Microscopy, Electron, Scanning Transmission ; Muscles/*cytology ; Oligonucleotide Array Sequence Analysis ; Zebrafish ; }, abstract = {The development of multicellular organisms is controlled by transcriptional networks. Understanding the role of these networks requires a full understanding of transcriptome regulation during embryogenesis. Several microarray studies have characterized the temporal evolution of the transcriptome during development in different organisms [Wang QT, et al. (2004) Dev Cell 6:133-144; Furlong EE, Andersen EC, Null B, White KP, Scott MP (2001) Science 293:1629-1633; Mitiku N, Baker JC (2007) Dev Cell 13:897-907]. In all cases, however, experiments were performed on whole embryos, thus averaging gene expression among many different tissues. Here, we took advantage of the local synchrony of the differentiation process in the paraxial mesoderm. This approach provides a unique opportunity to study the systems-level properties of muscle differentiation. Using high-resolution, spatiotemporal profiling of the early stages of muscle development in the zebrafish embryo, we identified a major reorganization of the transcriptome taking place in the presomitic mesoderm. We further show that the differentiation process is associated with a striking modular compartmentalization of the transcription of essential components of cellular physiological programs. Particularly, we identify a tight segregation of cell cycle/DNA metabolic processes and translation/oxidative metabolism at the tissue level, highly reminiscent of the yeast metabolic cycle. These results should expand more investigations into the developmental control of metabolism.}, } @article {pmid20143945, year = {2010}, author = {Sturdevant, DE and Virtaneva, K and Martens, C and Bozinov, D and Ogundare, O and Castro, N and Kanakabandi, K and Beare, PA and Omsland, A and Carlson, JH and Kennedy, AD and Heinzen, RA and Celli, J and Greenberg, DE and DeLeo, FR and Porcella, SF}, title = {Host-microbe interaction systems biology: lifecycle transcriptomics and comparative genomics.}, journal = {Future microbiology}, volume = {5}, number = {2}, pages = {205-219}, pmid = {20143945}, issn = {1746-0921}, support = {Z99 AI999999/ImNIH/Intramural NIH HHS/United States ; ZIC AI001052-02/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Comparative Genomic Hybridization/*methods ; Gene Expression Profiling/*methods ; *Host-Pathogen Interactions ; Humans ; Microarray Analysis/methods ; Sequence Analysis, DNA/methods ; Systems Biology/*methods ; }, abstract = {The use of microarray and comparative genomic technologies for the analysis of host-pathogen interactions has led to a greater understanding of the biological systems involved in infectious disease processes. Transcriptome analysis of intracellular pathogens at single or multiple time points during infection offers insight into the pathogen intracellular lifecycle. Host-pathogen transcriptome analysis in vivo, over time, enables characterization of both the pathogen and the host during the dynamic, multicellular host response. Comparative genomics using hybridization microarray-based comparative whole-genome resequencing or de novo whole-genome sequencing can identify the genetic factors responsible for pathogen evolutionary divergence, emergence, reemergence or the genetic basis for different pathogenic phenotypes. Together, microarray and comparative genomic technologies will continue to advance our understanding of pathogen evolution and assist in combating human infectious disease.}, } @article {pmid20128896, year = {2010}, author = {Alié, A and Manuel, M}, title = {The backbone of the post-synaptic density originated in a unicellular ancestor of choanoflagellates and metazoans.}, journal = {BMC evolutionary biology}, volume = {10}, number = {}, pages = {34}, pmid = {20128896}, issn = {1471-2148}, mesh = {Animals ; Choanoflagellata/*genetics ; Comparative Genomic Hybridization ; *Evolution, Molecular ; Nerve Tissue Proteins/*genetics ; Phylogeny ; Placozoa/*genetics ; Sequence Alignment ; Sequence Analysis, Protein ; }, abstract = {BACKGROUND: Comparative genomics of the early diverging metazoan lineages and of their unicellular sister-groups opens new window to reconstructing the genetic changes which preceded or accompanied the evolution of multicellular body plans. A recent analysis found that the genome of the nerve-less sponges encodes the homologues of most vertebrate post-synaptic proteins. In vertebrate excitatory synapses, these proteins assemble to form the post-synaptic density, a complex molecular platform linking membrane receptors, components of their signalling pathways, and the cytoskeleton. Newly available genomes from Monosiga brevicollis (a member of Choanoflagellata, the closest unicellular relatives of animals) and Trichoplax adhaerens (a member of Placozoa: besides sponges, the only nerve-less metazoans) offer an opportunity to refine our understanding of post-synaptic protein evolution.

RESULTS: Searches for orthologous proteins and reconstruction of gene gains/losses based on the taxon phylogeny indicate that post-synaptic proteins originated in two main steps. The backbone scaffold proteins (Shank, Homer, DLG) and some of their partners were acquired in a unicellular ancestor of choanoflagellates and metazoans. A substantial additional set appeared in an exclusive ancestor of the Metazoa. The placozoan genome contains most post-synaptic genes but lacks some of them. Notably, the master-scaffold protein Shank might have been lost secondarily in the placozoan lineage.

CONCLUSIONS: The time of origination of most post-synaptic proteins was not concomitant with the acquisition of synapses or neural-like cells. The backbone of the scaffold emerged in a unicellular context and was probably not involved in cell-cell communication. Based on the reconstructed protein composition and potential interactions, its ancestral function could have been to link calcium signalling and cytoskeleton regulation. The complex later became integrated into the evolving synapse through the addition of novel functionalities.}, } @article {pmid20124338, year = {2010}, author = {Ginger, ML and McFadden, GI and Michels, PA}, title = {The evolution of organellar metabolism in unicellular eukaryotes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {365}, number = {1541}, pages = {693-698}, pmid = {20124338}, issn = {1471-2970}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {*Biological Evolution ; Eukaryota/classification/*metabolism ; Organelles/*metabolism ; Phylogeny ; }, abstract = {Metabolic innovation has facilitated the radiation of microbes into almost every niche environment on the Earth, and over geological time scales transformed the planet on which we live. A notable example of innovation is the evolution of oxygenic photosynthesis which was a prelude to the gradual transformation of an anoxic Earth into a world with oxygenated oceans and an oxygen-rich atmosphere capable of supporting complex multicellular organisms. The influence of microbial innovation on the Earth's history and the timing of pivotal events have been addressed in other recent themed editions of Philosophical Transactions of Royal Society B (Cavalier-Smith et al. 2006; Bendall et al. 2008). In this issue, our contributors provide a timely history of metabolic innovation and adaptation within unicellular eukaryotes. In eukaryotes, diverse metabolic portfolios are compartmentalized across multiple membrane-bounded compartments (or organelles). However, as a consequence of pathway retargeting, organelle degeneration or novel endosymbiotic associations, the metabolic repertoires of protists often differ extensively from classic textbook descriptions of intermediary metabolism. These differences are often important in the context of niche adaptation or the structure of microbial communities. Fundamentally interesting in its own right, the biochemical, cell biological and phylogenomic investigation of organellar metabolism also has wider relevance. For instance, in some pathogens, notably those causing some of the most significant tropical diseases, including malaria, unusual organellar metabolism provides important new drug targets. Moreover, the study of organellar metabolism in protists continues to provide critical insight into our understanding of eukaryotic evolution.}, } @article {pmid20119528, year = {2009}, author = {Busca, A and Saxena, M and Kryworuchko, M and Kumar, A}, title = {Anti-apoptotic genes in the survival of monocytic cells during infection.}, journal = {Current genomics}, volume = {10}, number = {5}, pages = {306-317}, pmid = {20119528}, issn = {1875-5488}, abstract = {Macrophages are cells of the immune system that protect organisms against invading pathogens by fulfilling critical roles in innate and adaptive immunity and inflammation. They originate from circulating monocytes and show a high degree of heterogeneity, which reflects the specialization of function given by different anatomical locations. Differentiation of monocytes towards a macrophage phenotype is also accompanied by an increase of resistance against various apoptotic stimuli, a required characteristic that allows macrophages to accomplish their function in a stressful environment.Apoptosis, a form of programmed cell death, is a tightly regulated process, needed to maintain homeostasis by balancing proliferation with cellular demise. Caspases, a family of cysteine proteases that are highly conserved in multicellular organisms, function as central regulators of apoptosis. FLIP (FLICE-inhibitory protein), anti-apoptotic members of the Bcl2 family and inhibitors of apoptosis (IAP) are the main three groups of anti-apoptotic genes that counteract caspase activation through both the extrinsic and intrinsic apoptotic pathways.Modulation of the apoptotic machinery during viral and bacterial infections, as well as in various malignancies, is a wellestablished mechanism that promotes the survival of affected cells. The involvement of anti-apoptotic genes in the survival of monocytes/macrophages, either physiological or pathological, will be described in this review. How viral and bacterial infections that target cells of the monocytic lineage affect the expression of anti-apoptotic genes is important in understanding the pathological mechanisms that lead to manifested disease. The latest therapeutic approaches that target anti-apoptotic genes will also be discussed.}, } @article {pmid20091881, year = {2010}, author = {Tamerler, C and Khatayevich, D and Gungormus, M and Kacar, T and Oren, EE and Hnilova, M and Sarikaya, M}, title = {Molecular biomimetics: GEPI-based biological routes to technology.}, journal = {Biopolymers}, volume = {94}, number = {1}, pages = {78-94}, doi = {10.1002/bip.21368}, pmid = {20091881}, issn = {0006-3525}, mesh = {Animals ; *Biomimetic Materials/chemistry/metabolism ; *Biomimetics ; Computational Biology ; *Genetic Engineering ; Nature ; *Peptides/chemistry/genetics/metabolism ; Protein Conformation ; Protein Engineering ; }, abstract = {In nature, the viability of biological systems is sustained via specific interactions among the tens of thousands of proteins, the major building blocks of organisms from the simplest single-celled to the most complex multicellular species. Biomolecule-material interaction is accomplished with molecular specificity and efficiency leading to the formation of controlled structures and functions at all scales of dimensional hierarchy. Through evolution, Mother Nature developed molecular recognition by successive cycles of mutation and selection. Molecular specificity of probe-target interactions, e.g., ligand-receptor, antigen-antibody, is always based on specific peptide molecular recognition. Using biology as a guide, we can now understand, engineer, and control peptide-material interactions and exploit them as a new design tool for novel materials and systems. We adapted the protocols of combinatorially designed peptide libraries, via both cell surface or phage display methods; using these we select short peptides with specificity to a variety of practical materials. These genetically engineered peptides for inorganics (GEPI) are then studied experimentally to establish their binding kinetics and surface stability. The bound peptide structure and conformations are interrogated both experimentally and via modeling, and self-assembly characteristics are tested via atomic force microscopy. We further engineer the peptide binding and assembly characteristics using a computational biomimetics approach where bioinformatics based peptide-sequence similarity analysis is developed to design higher generation function-specific peptides. The molecular biomimetic approach opens up new avenues for the design and utilization of multifunctional molecular systems in a wide-range of applications from tissue engineering, disease diagnostics, and therapeutics to various areas of nanotechnology where integration is required among inorganic, organic and biological materials. Here, we describe lessons from biology with examples of protein-mediated functional biological materials, explain how novel peptides can be designed with specific affinity to inorganic solids using evolutionary engineering approaches, give examples of their potential utilizations in technology and medicine, and, finally, provide a summary of challenges and future prospects.}, } @article {pmid20091759, year = {2010}, author = {Miller, DJ and Technau, U}, title = {Understanding the evolution of multicellularity: insights from basal metazoans.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {32}, number = {2}, pages = {175-178}, doi = {10.1002/bies.200900168}, pmid = {20091759}, issn = {1521-1878}, support = {P 24858/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; *Biological Evolution ; Cell Differentiation ; Hydra/cytology ; }, } @article {pmid20089168, year = {2010}, author = {Verbruggen, H and Maggs, CA and Saunders, GW and Le Gall, L and Yoon, HS and De Clerck, O}, title = {Data mining approach identifies research priorities and data requirements for resolving the red algal tree of life.}, journal = {BMC evolutionary biology}, volume = {10}, number = {}, pages = {16}, pmid = {20089168}, issn = {1471-2148}, mesh = {Bayes Theorem ; DNA, Algal/genetics ; *Data Mining ; Evolution, Molecular ; Likelihood Functions ; Models, Genetic ; *Phylogeny ; Rhodophyta/classification/*genetics ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: The assembly of the tree of life has seen significant progress in recent years but algae and protists have been largely overlooked in this effort. Many groups of algae and protists have ancient roots and it is unclear how much data will be required to resolve their phylogenetic relationships for incorporation in the tree of life. The red algae, a group of primary photosynthetic eukaryotes of more than a billion years old, provide the earliest fossil evidence for eukaryotic multicellularity and sexual reproduction. Despite this evolutionary significance, their phylogenetic relationships are understudied. This study aims to infer a comprehensive red algal tree of life at the family level from a supermatrix containing data mined from GenBank. We aim to locate remaining regions of low support in the topology, evaluate their causes and estimate the amount of data required to resolve them.

RESULTS: Phylogenetic analysis of a supermatrix of 14 loci and 98 red algal families yielded the most complete red algal tree of life to date. Visualization of statistical support showed the presence of five poorly supported regions. Causes for low support were identified with statistics about the age of the region, data availability and node density, showing that poor support has different origins in different parts of the tree. Parametric simulation experiments yielded optimistic estimates of how much data will be needed to resolve the poorly supported regions (ca. 103 to ca. 104 nucleotides for the different regions). Nonparametric simulations gave a markedly more pessimistic image, some regions requiring more than 2.8 105 nucleotides or not achieving the desired level of support at all. The discrepancies between parametric and nonparametric simulations are discussed in light of our dataset and known attributes of both approaches.

CONCLUSIONS: Our study takes the red algae one step closer to meaningful inclusion in the tree of life. In addition to the recovery of stable relationships, the recognition of five regions in need of further study is a significant outcome of this work. Based on our analyses of current availability and future requirements of data, we make clear recommendations for forthcoming research.}, } @article {pmid20084108, year = {2010}, author = {Park, Y and Moore, C and Bader, JS}, title = {Dynamic networks from hierarchical bayesian graph clustering.}, journal = {PloS one}, volume = {5}, number = {1}, pages = {e8118}, pmid = {20084108}, issn = {1932-6203}, mesh = {Algorithms ; *Bayes Theorem ; *Cluster Analysis ; TATA-Box Binding Protein/metabolism ; }, abstract = {Biological networks change dynamically as protein components are synthesized and degraded. Understanding the time-dependence and, in a multicellular organism, tissue-dependence of a network leads to insight beyond a view that collapses time-varying interactions into a single static map. Conventional algorithms are limited to analyzing evolving networks by reducing them to a series of unrelated snapshots.Here we introduce an approach that groups proteins according to shared interaction patterns through a dynamical hierarchical stochastic block model. Protein membership in a block is permitted to evolve as interaction patterns shift over time and space, representing the spatial organization of cell types in a multicellular organism. The spatiotemporal evolution of the protein components are inferred from transcript profiles, using Arabidopsis root development (5 tissues, 3 temporal stages) as an example.The new model requires essentially no parameter tuning, out-performs existing snapshot-based methods, identifies protein modules recruited to specific cell types and developmental stages, and could have broad application to social networks and other similar dynamic systems.}, } @article {pmid20081368, year = {2010}, author = {Lane, DP and Cheok, CF and Brown, C and Madhumalar, A and Ghadessy, FJ and Verma, C}, title = {Mdm2 and p53 are highly conserved from placozoans to man.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {9}, number = {3}, pages = {540-547}, doi = {10.4161/cc.9.3.10516}, pmid = {20081368}, issn = {1551-4005}, mesh = {Amino Acid Sequence ; Animals ; *Conserved Sequence ; Humans ; Models, Molecular ; Molecular Sequence Data ; Placozoa/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Proto-Oncogene Proteins c-mdm2/*chemistry ; Sequence Alignment ; Tumor Suppressor Protein p53/*chemistry ; }, abstract = {The p53 protein is the most commonly mutated tumor suppressor gene in man. Understanding of its evolutionary origins have been enhanced by the recent discovery of p53 family genes in the Sea Anemone Nematostella vectensis. This amino acid sequence conservation has been reflected in biological activity since the early p53 proteins, like their human counterparts, are responsible for DNA damage-induced cellular apoptosis, albeit restricted to the germ cell compartment in model organisms such as the nematode and fruit fly. In vertebrates from zebrafish to man the function of p53 is tightly and absolutely constrained by a negative regulator Mdm2. However the Mdm2 gene has not been detected in the genome of the model nematode (C. elegans) and insect (D. melanogaster) species. We have found that the p53 gene and the Mdm2 gene are present in Placozoans, one of the simplest of all free living multi-cellular organisms, implying that both proteins arose much earlier in evolution than previously thought. Detailed sequence analysis shows the exceptional retention of key features of both proteins from man to Placazoan implying that the p53-Mdm2 interaction and its regulation have been conserved from a basal eumetazoan since the pre-cambrian era over 1 billion years ago.}, } @article {pmid20078651, year = {2010}, author = {Funayama, N}, title = {The stem cell system in demosponges: insights into the origin of somatic stem cells.}, journal = {Development, growth & differentiation}, volume = {52}, number = {1}, pages = {1-14}, doi = {10.1111/j.1440-169X.2009.01162.x}, pmid = {20078651}, issn = {1440-169X}, mesh = {Animals ; Body Patterning/genetics ; *Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Gene Expression Regulation, Developmental ; Models, Biological ; Porifera/*cytology/embryology/growth & development ; RNA, Small Interfering/genetics ; Stem Cells/*cytology/metabolism ; }, abstract = {The stem cell system is one of the unique systems that have evolved only in multicellular organisms. Major questions about this system include what type(s) of stem cells are involved (pluri-, multi- or uni-potent stem cells), and how the self-renewal and differentiation of stem cells are regulated. To understand the origin of the stem cell system in metazoans and to get insights into the ancestral stem cell itself, it is important to discover the molecular and cellular mechanisms of the stem cell system in sponges (Porifera), the evolutionarily oldest extant metazoans. Histological studies here provided a body of evidence that archeocytes are the stem cells in sponges, and recent molecular studies of sponges, especially the finding of the expression of Piwi homologues in archeocytes and choanocytes in a freshwater sponge, Ephydatia fluviatilis, have provided critical insights into the stem cell system in demosponges. Here I introduce archeocytes and discuss (i) modes of archeocyte differentiation, (ii) our current model of the stem cell system in sponges composed of both archeocytes and choanocytes based on our molecular analysis and previous microscopic studies suggesting the maintenance of pluripotency in choanocytes, (iii) the inference that the Piwi and piRNA function in maintaining stem cells (which also give rise to gametes) may have already been achieved in the ancestral metazoan, and (iv) possible hypotheses about how the migrating stem cells arose in the urmetazoan (protometazoan) and about the evolutionary origin of germline cells in the urbilaterian (protobilaterian).}, } @article {pmid20067403, year = {2010}, author = {Jones, J}, title = {Characteristics of pattern formation and evolution in approximations of Physarum transport networks.}, journal = {Artificial life}, volume = {16}, number = {2}, pages = {127-153}, doi = {10.1162/artl.2010.16.2.16202}, pmid = {20067403}, issn = {1064-5462}, mesh = {Chemotaxis ; Diffusion ; Physarum polycephalum/*metabolism ; }, abstract = {Most studies of pattern formation place particular emphasis on its role in the development of complex multicellular body plans. In simpler organisms, however, pattern formation is intrinsic to growth and behavior. Inspired by one such organism, the true slime mold Physarum polycephalum, we present examples of complex emergent pattern formation and evolution formed by a population of simple particle-like agents. Using simple local behaviors based on chemotaxis, the mobile agent population spontaneously forms complex and dynamic transport networks. By adjusting simple model parameters, maps of characteristic patterning are obtained. Certain areas of the parameter mapping yield particularly complex long term behaviors, including the circular contraction of network lacunae and bifurcation of network paths to maintain network connectivity. We demonstrate the formation of irregular spots and labyrinthine and reticulated patterns by chemoattraction. Other Turing-like patterning schemes were obtained by using chemorepulsion behaviors, including the self-organization of regular periodic arrays of spots, and striped patterns. We show that complex pattern types can be produced without resorting to the hierarchical coupling of reaction-diffusion mechanisms. We also present network behaviors arising from simple pre-patterning cues, giving simple examples of how the emergent pattern formation processes evolve into networks with functional and quasi-physical properties including tensionlike effects, network minimization behavior, and repair to network damage. The results are interpreted in relation to classical theories of biological pattern formation in natural systems, and we suggest mechanisms by which emergent pattern formation processes may be used as a method for spatially represented unconventional computation.}, } @article {pmid20059450, year = {2010}, author = {Michelet, X and Djeddi, A and Legouis, R}, title = {Developmental and cellular functions of the ESCRT machinery in pluricellular organisms.}, journal = {Biology of the cell}, volume = {102}, number = {3}, pages = {191-202}, doi = {10.1042/BC20090145}, pmid = {20059450}, issn = {1768-322X}, mesh = {Animals ; Cell Differentiation/*physiology ; Endosomal Sorting Complexes Required for Transport/*genetics/*metabolism/ultrastructure ; Endosomes/*metabolism/ultrastructure ; Evolution, Molecular ; Gene Expression Regulation, Developmental/physiology ; Lysosomes/*metabolism/ultrastructure ; Models, Animal ; Multivesicular Bodies/metabolism/ultrastructure ; Protein Transport/physiology ; Signal Transduction/*physiology ; }, abstract = {ESCRTs (endosomal sorting complexes required for transport) were first discovered in yeast and are known to be required in the biogenesis of the MVB (multivesicular body). Most ESCRT research has been carried out in vitro using models such as yeast and mammalian cells in culture. The role of the ESCRTs genes in endosome maturation is conserved from yeast to mammals, but little is known about their function during development in multicellular organisms. Since ESCRTs play a leading role in regulating some cell signalling pathways by addressing receptors to the lysosome, it appears important to monitor ESCRT functions in multicellular models. The present review summarizes recent research on the developmental and cellular functions of the ESCRT in Caenorhabditis elegans, Drosophila melanogaster, Mus musculus or Arabidopsis thaliana.}, } @article {pmid20054405, year = {2009}, author = {Omelyanchuk, LV and Pertseva, JA and Burns, SS and Chang, LS}, title = {Evolution and origin of HRS, a protein interacting with Merlin, the Neurofibromatosis 2 gene product.}, journal = {Gene regulation and systems biology}, volume = {3}, number = {}, pages = {143-157}, pmid = {20054405}, issn = {1177-6250}, abstract = {Hepatocyte growth factor receptor tyrosine kinase substrate (HRS) is an endosomal protein required for trafficking receptor tyrosine kinases from the early endosome to the lysosome. HRS interacts with Merlin, the Neurofibromatosis 2 (NF2) gene product, and this interaction may be important for Merlin's tumor suppressor activity. Understanding the evolution, origin, and structure of HRS may provide new insight into Merlin function. We show that HRS homologs are present across a wide range of Metazoa with the yeast Vps27 protein as their most distant ancestor. The phylogenetic tree of the HRS family coincides with species evolution and divergence, suggesting a unique function for HRS. Sequence alignment shows that various protein domains of HRS, including the VHS domain, the FYVE domain, the UIM domain, and the clathrin-binding domain, are conserved from yeast to multicellular organisms. The evolutionary transition from unicellular to multicellular organisms was accompanied by the appearance of a binding site for Merlin, which emerges in the early Metazoa after its separation from flatworms. In addition to the region responsible for growth suppression, the Merlin-binding and STAM-binding domains of HRS are conserved among multicellular organisms. The residue equivalent to tyrosine-377, which is phosphorylated in the human HRS protein, is highly conserved throughout the HRS family. Three additional conserved boxes lacking assigned functions are found in the HRS proteins of Metazoa. While boxes 1 and 3 may constitute the Eps-15-and Snx1-binding sites, respectively, box 2, containing the residue equivalent to tyrosine-377, is likely to be important for HRS phosphorylation. While several functional domains are conserved throughout the HRS family, the STAM-binding, Merlin-binding, and growth suppression domains evolved in the early Metazoa around the time the Merlin protein emerged. As these domains appear during the transition to multicellularity, their functional roles may be related to cell-cell interaction.}, } @article {pmid20053372, year = {2010}, author = {Medina, M and Sachs, JL}, title = {Symbiont genomics, our new tangled bank.}, journal = {Genomics}, volume = {95}, number = {3}, pages = {129-137}, doi = {10.1016/j.ygeno.2009.12.004}, pmid = {20053372}, issn = {1089-8646}, mesh = {Animals ; *Bacteria/genetics/growth & development ; Ecosystem ; *Eukaryota/genetics/growth & development ; Evolution, Molecular ; Genomics ; Humans ; *Metagenomics ; *Symbiosis ; }, abstract = {Microbial symbionts inhabit the soma and surfaces of most multicellular species and instigate both beneficial and harmful infections. Despite their ubiquity, we are only beginning to resolve major patterns of symbiont ecology and evolution. Here, we summarize the history, current progress, and projected future of the study of microbial symbiont evolution throughout the tree of life. We focus on the recent surge of data that whole-genome sequencing has introduced into the field, in particular the links that are now being made between symbiotic lifestyle and molecular evolution. Post-genomic and systems biology approaches are also emerging as powerful techniques to investigate host-microbe interactions, both at the molecular level of the species interface and at the global scale. In parallel, next-generation sequencing technologies are allowing new questions to be addressed by providing access to population genomic data, as well as the much larger genomes of microbial eukaryotic symbionts and hosts. Throughout we describe the questions that these techniques are tackling and we conclude by listing a series of unanswered questions in microbial symbiosis that can potentially be addressed with the new technologies.}, } @article {pmid20053306, year = {2009}, author = {Krecek, P and Skupa, P and Libus, J and Naramoto, S and Tejos, R and Friml, J and Zazímalová, E}, title = {The PIN-FORMED (PIN) protein family of auxin transporters.}, journal = {Genome biology}, volume = {10}, number = {12}, pages = {249}, pmid = {20053306}, issn = {1474-760X}, mesh = {Arabidopsis/*genetics ; Arabidopsis Proteins/*genetics/metabolism ; *Evolution, Molecular ; Gene Expression Profiling ; Indoleacetic Acids/*metabolism ; Membrane Transport Proteins/*genetics/metabolism ; *Models, Molecular ; Multigene Family/*genetics ; *Phylogeny ; Protein Conformation ; }, abstract = {The PIN-FORMED (PIN) proteins are secondary transporters acting in the efflux of the plant signal molecule auxin from cells. They are asymmetrically localized within cells and their polarity determines the directionality of intercellular auxin flow. PIN genes are found exclusively in the genomes of multicellular plants and play an important role in regulating asymmetric auxin distribution in multiple developmental processes, including embryogenesis, organogenesis, tissue differentiation and tropic responses. All PIN proteins have a similar structure with amino- and carboxy-terminal hydrophobic, membrane-spanning domains separated by a central hydrophilic domain. The structure of the hydrophobic domains is well conserved. The hydrophilic domain is more divergent and it determines eight groups within the protein family. The activity of PIN proteins is regulated at multiple levels, including transcription, protein stability, subcellular localization and transport activity. Different endogenous and environmental signals can modulate PIN activity and thus modulate auxin-distribution-dependent development. A large group of PIN proteins, including the most ancient members known from mosses, localize to the endoplasmic reticulum and they regulate the subcellular compartmentalization of auxin and thus auxin metabolism. Further work is needed to establish the physiological importance of this unexpected mode of auxin homeostasis regulation. Furthermore, the evolution of PIN-based transport, PIN protein structure and more detailed biochemical characterization of the transport function are important topics for further studies.}, } @article {pmid20045679, year = {2010}, author = {Zeitlinger, J and Stark, A}, title = {Developmental gene regulation in the era of genomics.}, journal = {Developmental biology}, volume = {339}, number = {2}, pages = {230-239}, doi = {10.1016/j.ydbio.2009.12.039}, pmid = {20045679}, issn = {1095-564X}, mesh = {Animals ; Chromatin/metabolism ; Drosophila Proteins/genetics/metabolism ; *Gene Expression Regulation, Developmental ; Genes, Insect ; *Genome ; Genomics/methods/*trends ; Humans ; Models, Biological ; RNA Polymerase II/genetics/metabolism ; }, abstract = {Genetic experiments over the last few decades have identified many developmental control genes critical for pattern formation and cell fate specification during the development of multicellular organisms. A large fraction of these genes encode transcription factors and signaling molecules, show highly dynamic expression patterns during development, and are deeply evolutionarily conserved and deregulated in various human diseases such as cancer. Because of their importance in development, evolution, and disease, a fundamental question in biology is how these developmental control genes are regulated in such an extensive and precise fashion. Using genomics methods, it has become clear that developmental control genes are a distinct group of genes with special regulatory characteristics. However, a systematic analysis of these characteristics has not been presented. Here we review how developmental control genes were discovered, evaluate their genome-wide regulation and gene structure, discuss emerging evidence for their mode of regulation, and estimate their overall abundance in the genome. Understanding the global regulation of developmental control genes may provide a new perspective on development in the era genomics.}, } @article {pmid20039865, year = {2010}, author = {Tan, DX and Hardeland, R and Manchester, LC and Paredes, SD and Korkmaz, A and Sainz, RM and Mayo, JC and Fuentes-Broto, L and Reiter, RJ}, title = {The changing biological roles of melatonin during evolution: from an antioxidant to signals of darkness, sexual selection and fitness.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {85}, number = {3}, pages = {607-623}, doi = {10.1111/j.1469-185X.2009.00118.x}, pmid = {20039865}, issn = {1469-185X}, mesh = {Animals ; Antioxidants/metabolism ; *Biological Evolution ; Darkness ; Gene Expression Regulation/*physiology ; Genetic Fitness/genetics/*physiology ; Mating Preference, Animal/*physiology ; Melatonin/genetics/*metabolism ; Plants/metabolism ; Signal Transduction/*physiology ; }, abstract = {Melatonin is a molecule present in a multitude of taxa and may be ubiquitous in organisms. It has been found in bacteria, unicellular eukaryotes, macroalgae, fungi, plants and animals. A primary biological function of melatonin in primitive unicellular organisms is in antioxidant defence to protect against toxic free radical damage. During evolution, melatonin has been adopted by multicellular organisms to perform many other biological functions. These functions likely include the chemical expression of darkness in vertebrates, environmental tolerance in fungi and plants, sexual signaling in birds and fish, seasonal reproductive regulation in photoperiodic mammals, and immunomodulation and anti-inflammatory activity in all vertebrates tested. Moreover, its waning production during aging may indicate senescence in terms of a bio-clock in many organisms. Conversely, high melatonin levels can serve as a signal of vitality and health. The multiple biological functions of melatonin can partially be attributed to its unconventional metabolism which is comprised of multi-enzymatic, pseudo-enzymatic and non-enzymatic pathways. As a result, several bioactive metabolites of melatonin are formed during its metabolism and some of the presumed biological functions of melatonin reported to date may, in fact, be mediated by these metabolites. The changing biological roles of melatonin seem to have evolved from its primary function as an antioxidant.}, } @article {pmid20021546, year = {2010}, author = {Paz-Y-Miño C, G and Espinosa, A}, title = {Integrating horizontal gene transfer and common descent to depict evolution and contrast it with "common design".}, journal = {The Journal of eukaryotic microbiology}, volume = {57}, number = {1}, pages = {11-18}, pmid = {20021546}, issn = {1550-7408}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; P20 RR016457/RR/NCRR NIH HHS/United States ; P20RR16457-04/RR/NCRR NIH HHS/United States ; }, mesh = {Alcohol Dehydrogenase/genetics ; Aldehyde Dehydrogenase/genetics ; Animals ; Biodiversity ; Entamoeba histolytica/enzymology/genetics ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; Humans ; Models, Genetic ; Phylogeny ; Selection, Genetic ; }, abstract = {Horizontal gene transfer (HGT) and common descent interact in space and time. Because events of HGT co-occur with phylogenetic evolution, it is difficult to depict evolutionary patterns graphically. Tree-like representations of life's diversification are useful, but they ignore the significance of HGT in evolutionary history, particularly of unicellular organisms, ancestors of multicellular life. Here we integrate the reticulated-tree model, ring of life, symbiogenesis whole-organism model, and eliminative pattern pluralism to represent evolution. Using Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2), a bifunctional enzyme in the glycolytic pathway of amoeba, we illustrate how EhADH2 could be the product of both horizontally acquired features from ancestral prokaryotes (i.e. aldehyde dehydrogenase [ALDH] and alcohol dehydrogenase [ADH]), and subsequent functional integration of these enzymes into EhADH2, which is now inherited by amoeba via common descent. Natural selection has driven the evolution of EhADH2 active sites, which require specific amino acids (cysteine 252 in the ALDH domain; histidine 754 in the ADH domain), iron- and NAD(+) as cofactors, and the substrates acetyl-CoA for ALDH and acetaldehyde for ADH. Alternative views invoking "common design" (i.e. the non-naturalistic emergence of major taxa independent from ancestry) to explain the interaction between horizontal and vertical evolution are unfounded.}, } @article {pmid20008382, year = {2010}, author = {Nowak, MA and Tarnita, CE and Antal, T}, title = {Evolutionary dynamics in structured populations.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {365}, number = {1537}, pages = {19-30}, pmid = {20008382}, issn = {1471-2970}, support = {R01 GM078986/GM/NIGMS NIH HHS/United States ; R01GM078986/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; *Cooperative Behavior ; *Ecosystem ; Game Theory ; Humans ; Philosophy ; *Population Dynamics ; Stochastic Processes ; }, abstract = {Evolutionary dynamics shape the living world around us. At the centre of every evolutionary process is a population of reproducing individuals. The structure of that population affects evolutionary dynamics. The individuals can be molecules, cells, viruses, multicellular organisms or humans. Whenever the fitness of individuals depends on the relative abundance of phenotypes in the population, we are in the realm of evolutionary game theory. Evolutionary game theory is a general approach that can describe the competition of species in an ecosystem, the interaction between hosts and parasites, between viruses and cells, and also the spread of ideas and behaviours in the human population. In this perspective, we review the recent advances in evolutionary game dynamics with a particular emphasis on stochastic approaches in finite sized and structured populations. We give simple, fundamental laws that determine how natural selection chooses between competing strategies. We study the well-mixed population, evolutionary graph theory, games in phenotype space and evolutionary set theory. We apply these results to the evolution of cooperation. The mechanism that leads to the evolution of cooperation in these settings could be called 'spatial selection': cooperators prevail against defectors by clustering in physical or other spaces.}, } @article {pmid19995574, year = {2010}, author = {Rimphanitchayakit, V and Tassanakajon, A}, title = {Structure and function of invertebrate Kazal-type serine proteinase inhibitors.}, journal = {Developmental and comparative immunology}, volume = {34}, number = {4}, pages = {377-386}, doi = {10.1016/j.dci.2009.12.004}, pmid = {19995574}, issn = {1879-0089}, mesh = {Animals ; Drosophila Proteins/*physiology ; Evolution, Molecular ; Host-Pathogen Interactions ; Infections/*enzymology/immunology ; Invertebrates/microbiology/*physiology ; Protein Conformation ; Protein Structure, Tertiary/physiology ; Serine Proteinase Inhibitors/pharmacology/*physiology ; Substrate Specificity ; }, abstract = {Proteinases and proteinase inhibitors are involved in several biological and physiological processes in all multicellular organisms. The proteinase inhibitors function as modulators for controlling the extent of deleterious proteinase activity. The Kazal-type proteinase inhibitors (KPIs) in family I1 are among the well-known families of proteinase inhibitors, widely found in mammals, avian and a variety of invertebrates. Like those classical KPIs, the invertebrate KPIs can be single or multiple domain proteins containing one or more Kazal inhibitory domains linked together by peptide spacers of variable length. All invertebrate Kazal domains of about 40-60 amino acids in length share a common structure which is dictated by six conserved cysteine residues forming three intra-domain disulfide cross-links despite the variability of amino acid sequences between the half-cystines. Invertebrate KPIs are strong inhibitors as shown by their extremely high association constant of 10(7)-10(13)M(-1). The inhibitory specificity of a Kazal domain varies widely with a different reactive P(1) amino acid. Different invertebrate KPI domains may arise from gene duplication but several KPI proteins can also be derived from alternative splicing. The invertebrate KPIs function as anticoagulants in blood-sucking animals such as leech, mosquitoes and ticks. Several KPIs are likely involved in protecting host from microbial proteinases while some from the parasitic protozoa help protecting the parasites from the host digestive proteinase enzymes. Silk moths produce KPIs to protect their cocoon from predators and microbial destruction.}, } @article {pmid19995431, year = {2009}, author = {Prat, Y and Fromer, M and Linial, N and Linial, M}, title = {Codon usage is associated with the evolutionary age of genes in metazoan genomes.}, journal = {BMC evolutionary biology}, volume = {9}, number = {}, pages = {285}, pmid = {19995431}, issn = {1471-2148}, mesh = {Animals ; Base Composition ; *Codon ; *Evolution, Molecular ; *Genome ; Humans ; }, abstract = {BACKGROUND: Codon usage may vary significantly between different organisms and between genes within the same organism. Several evolutionary processes have been postulated to be the predominant determinants of codon usage: selection, mutation, and genetic drift. However, the relative contribution of each of these factors in different species remains debatable. The availability of complete genomes for tens of multicellular organisms provides an opportunity to inspect the relationship between codon usage and the evolutionary age of genes.

RESULTS: We assign an evolutionary age to a gene based on the relative positions of its identified homologues in a standard phylogenetic tree. This yields a classification of all genes in a genome to several evolutionary age classes. The present study starts from the observation that each age class of genes has a unique codon usage and proceeds to provide a quantitative analysis of the codon usage in these classes. This observation is made for the genomes of Homo sapiens, Mus musculus, and Drosophila melanogaster. It is even more remarkable that the differences between codon usages in different age groups exhibit similar and consistent behavior in various organisms. While we find that GC content and gene length are also associated with the evolutionary age of genes, they can provide only a partial explanation for the observed codon usage.

CONCLUSION: While factors such as GC content, mutational bias, and selection shape the codon usage in a genome, the evolutionary history of an organism over hundreds of millions of years is an overlooked property that is strongly linked to GC content, protein length, and, even more significantly, to the codon usage of metazoan genomes.}, } @article {pmid19966815, year = {2010}, author = {Flores, E and Herrero, A}, title = {Compartmentalized function through cell differentiation in filamentous cyanobacteria.}, journal = {Nature reviews. Microbiology}, volume = {8}, number = {1}, pages = {39-50}, pmid = {19966815}, issn = {1740-1534}, mesh = {Cyanobacteria/classification/genetics/*physiology ; Genome, Bacterial ; Models, Biological ; Nitrogen Fixation ; Oxygen/*metabolism ; *Photosynthesis ; Phylogeny ; Signal Transduction ; }, abstract = {Within the wide biodiversity that is found in the bacterial world, Cyanobacteria represents a unique phylogenetic group that is responsible for a key metabolic process in the biosphere - oxygenic photosynthesis - and that includes representatives exhibiting complex morphologies. Many cyanobacteria are multicellular, growing as filaments of cells in which some cells can differentiate to carry out specialized functions. These differentiated cells include resistance and dispersal forms as well as a metabolically specialized form that is devoted to N(2) fixation, known as the heterocyst. In this Review we address cyanobacterial intercellular communication, the supracellular structure of the cyanobacterial filament and the basic principles that govern the process of heterocyst differentiation.}, } @article {pmid19956794, year = {2009}, author = {Lapraz, F and Besnardeau, L and Lepage, T}, title = {Patterning of the dorsal-ventral axis in echinoderms: insights into the evolution of the BMP-chordin signaling network.}, journal = {PLoS biology}, volume = {7}, number = {11}, pages = {e1000248}, pmid = {19956794}, issn = {1545-7885}, mesh = {Animals ; *Biological Evolution ; *Body Patterning ; Bone Morphogenetic Protein Receptors/metabolism ; Bone Morphogenetic Proteins/antagonists & inhibitors/*metabolism ; Echinodermata/*embryology/metabolism ; Ectoderm/embryology ; Gene Expression Regulation, Developmental ; Glycoproteins/*metabolism ; Glypicans/metabolism ; Intercellular Signaling Peptides and Proteins/*metabolism ; Nodal Protein/*metabolism ; Signal Transduction ; Smad Proteins, Receptor-Regulated/metabolism ; }, abstract = {Formation of the dorsal-ventral axis of the sea urchin embryo relies on cell interactions initiated by the TGFbeta Nodal. Intriguingly, although nodal expression is restricted to the ventral side of the embryo, Nodal function is required for specification of both the ventral and the dorsal territories and is able to restore both ventral and dorsal regions in nodal morpholino injected embryos. The molecular basis for the long-range organizing activity of Nodal is not understood. In this paper, we provide evidence that the long-range organizing activity of Nodal is assured by a relay molecule synthesized in the ventral ectoderm, then translocated to the opposite side of the embryo. We identified this relay molecule as BMP2/4 based on the following arguments. First, blocking BMP2/4 function eliminated the long-range organizing activity of an activated Nodal receptor in an axis rescue assay. Second, we demonstrate that BMP2/4 and the corresponding type I receptor Alk3/6 functions are both essential for specification of the dorsal region of the embryo. Third, using anti-phospho-Smad1/5/8 immunostaining, we show that, despite its ventral transcription, the BMP2/4 ligand triggers receptor mediated signaling exclusively on the dorsal side of the embryo, one of the most extreme cases of BMP translocation described so far. We further report that the pattern of pSmad1/5/8 is graded along the dorsal-ventral axis and that two BMP2/4 target genes are expressed in nested patterns centered on the region with highest levels of pSmad1/5/8, strongly suggesting that BMP2/4 is acting as a morphogen. We also describe the very unusual ventral co-expression of chordin and bmp2/4 downstream of Nodal and demonstrate that Chordin is largely responsible for the spatial restriction of BMP2/4 signaling to the dorsal side. Thus, unlike in most organisms, in the sea urchin, a single ventral signaling centre is responsible for induction of ventral and dorsal cell fates. Finally, we show that Chordin may not be required for long-range diffusion of BMP2/4, describe a striking dorsal-ventral asymmetry in the expression of Glypican 5, a heparin sulphated proteoglycan that regulates BMP mobility, and show that this asymmetry depends on BMP2/4 signaling. Our study provides new insights into the mechanisms by which positional information is established along the dorsal-ventral axis of the sea urchin embryo, and more generally on how a BMP morphogen gradient is established in a multicellular embryo. From an evolutionary point of view, it highlights that although the genes used for dorsal-ventral patterning are highly conserved in bilateria, there are considerable variations, even among deuterostomes, in the manner these genes are used to shape a BMP morphogen gradient.}, } @article {pmid19948791, year = {2009}, author = {Dissmeyer, N and Weimer, AK and Pusch, S and De Schutter, K and Alvim Kamei, CL and Nowack, MK and Novak, B and Duan, GL and Zhu, YG and De Veylder, L and Schnittger, A}, title = {Control of cell proliferation, organ growth, and DNA damage response operate independently of dephosphorylation of the Arabidopsis Cdk1 homolog CDKA;1.}, journal = {The Plant cell}, volume = {21}, number = {11}, pages = {3641-3654}, pmid = {19948791}, issn = {1532-298X}, mesh = {Arabidopsis/*genetics/growth & development/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Binding Sites/genetics ; CDC2 Protein Kinase/genetics/metabolism ; Cell Cycle/genetics ; Cell Cycle Proteins/*genetics/metabolism ; *Cell Proliferation ; Cyclin-Dependent Kinases/*genetics/metabolism ; DNA Damage/*genetics ; DNA Repair/*genetics ; Evolution, Molecular ; Genes, cdc/physiology ; Mathematics ; Mitosis/genetics ; Phosphorylation ; Plant Structures/genetics/growth & development/metabolism ; cdc25 Phosphatases/genetics/metabolism ; }, abstract = {Entry into mitosis is universally controlled by cyclin-dependent kinases (CDKs). A key regulatory event in metazoans and fission yeast is CDK activation by the removal of inhibitory phosphate groups in the ATP binding pocket catalyzed by Cdc25 phosphatases. In contrast with other multicellular organisms, we show here that in the flowering plant Arabidopsis thaliana, cell cycle control does not depend on sudden changes in the phosphorylation pattern of the PSTAIRE-containing Cdk1 homolog CDKA;1. Consistently, we found that neither mutants in a previously identified CDC25 candidate gene nor plants in which it is overexpressed display cell cycle defects. Inhibitory phosphorylation of CDKs is also the key event in metazoans to arrest cell cycle progression upon DNA damage. However, we show here that the DNA damage checkpoint in Arabidopsis can also operate independently of the phosphorylation of CDKA;1. These observations reveal a surprising degree of divergence in the circuitry of highly conserved core cell cycle regulators in multicellular organisms. Based on biomathematical simulations, we propose a plant-specific model of how progression through the cell cycle could be wired in Arabidopsis.}, } @article {pmid19934432, year = {2009}, author = {Hill, DA and Artis, D}, title = {Maintaining diplomatic relations between mammals and beneficial microbial communities.}, journal = {Science signaling}, volume = {2}, number = {98}, pages = {pe77}, pmid = {19934432}, issn = {1937-9145}, support = {R01 AI074878/AI/NIAID NIH HHS/United States ; R01 AI095466/AI/NIAID NIH HHS/United States ; T32 AI007532/AI/NIAID NIH HHS/United States ; T32 CA009140/CA/NCI NIH HHS/United States ; S10 RR024525/RR/NCRR NIH HHS/United States ; T32 AI055438/AI/NIAID NIH HHS/United States ; F31 GM082187/GM/NIGMS NIH HHS/United States ; R01 AI074878-02/AI/NIAID NIH HHS/United States ; R01 AI061570/AI/NIAID NIH HHS/United States ; F32 AI072943/AI/NIAID NIH HHS/United States ; R01 AI061570-06/AI/NIAID NIH HHS/United States ; T32 AI060516/AI/NIAID NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Animals ; Bacteria/*immunology ; Bacterial Adhesion/immunology ; Humans ; *Immune System ; Immunity, Innate ; Inflammation ; Inflammatory Bowel Diseases/immunology ; Intestinal Mucosa/*microbiology ; Mammals/immunology ; Mice ; Signal Transduction ; Symbiosis/immunology ; Toll-Like Receptors/metabolism ; }, abstract = {The first reports of diplomatic relations between human communities date back to the 14th century B.C.E. and the age of the Egyptian pharaohs. However, the evolution of analogous relations between mammals and mutualistic microbial communities is as old as multicellular organisms themselves. A fundamental issue surrounding the biology of these mutualistic relationships is how the immune system recognizes beneficial microbes and tolerates their colonization of barrier surfaces while simultaneously preventing their outgrowth and potentially lethal dissemination throughout the host. New evidence provides insight into the molecular mechanisms that orchestrate diplomacy between the mammalian immune system and bacterial communities in the gut.}, } @article {pmid19930629, year = {2009}, author = {Vestby, LK and Møretrø, T and Ballance, S and Langsrud, S and Nesse, LL}, title = {Survival potential of wild type cellulose deficient Salmonella from the feed industry.}, journal = {BMC veterinary research}, volume = {5}, number = {}, pages = {43}, pmid = {19930629}, issn = {1746-6148}, mesh = {Animal Feed/*microbiology ; Animals ; Bacterial Typing Techniques ; Biofilms ; Cellulose/*metabolism ; Colony Count, Microbial ; Disinfectants/pharmacology ; *Food Industry ; Humans ; *Industrial Microbiology ; Phenotype ; Polysaccharides, Bacterial/analysis ; Salmonella/drug effects/enzymology/growth & development/*physiology ; Time Factors ; }, abstract = {BACKGROUND: Biofilm has been shown to be one way for Salmonella to persist in the feed factory environment. Matrix components, such as fimbriae and cellulose, have been suggested to play an important role in the survival of Salmonella in the environment. Multicellular behaviour by Salmonella is often categorized according to colony morphology into rdar (red, dry and rough) expressing curli fimbriae and cellulose, bdar (brown, dry and rough) expressing curli fimbriae and pdar (pink, dry and rough) expressing cellulose. The aim of the study was to look into the distribution of morphotypes among feed and fish meal factory strains of Salmonella, with emphasis on potential differences between morphotypes with regards to survival in the feed factory environment.

RESULTS: When screening a total of 148 Salmonella ser. Agona, Salmonella ser. Montevideo, Salmonella ser. Senftenberg and Salmonella ser. Typhimurium strains of feed factory, human clinical and reference collection origin, as many as 99% were able to express rough morphology (rdar or bdar). The dominant morphotype was rdar (74%), however as many as 55% of Salmonella ser. Agona and 19% of Salmonella ser. Senftenberg displayed the bdar morphology. Inconsistency in Calcofluor binding, indicating expression of cellulose, was found among 25% of all the strains tested, however Salmonella ser. Agona showed to be highly consistent in Calcofluor binding (98%). In biofilm, Salmonella ser. Agona strains with bdar mophology was found to be equally tolerant to disinfection treatment as strains with rdar morphotype. However, rdar morphology appeared to be favourable in long term survival in biofilm in a very dry environment. Chemical analysis showed no major differences in polysaccharide content between bdar and rdar strains. Our results indicate that cellulose is not a major component of the Salmonella biofilm matrix.

CONCLUSION: The bdar morphotype is common among Salmonella ser. Agona strains isolated from the factory environment. The rdar and the bdar strains were found to be equally tolerant to disinfectants, while the rdar strain was found to be more tolerant to long-term desiccation and nutrient depletion in biofilm than the bdar strain. Cellulose does not appear to be a major component of the Salmonella biofilm matrix.}, } @article {pmid19929876, year = {2010}, author = {Hu, Z and Qin, Z and Wang, M and Xu, C and Feng, G and Liu, J and Meng, Z and Hu, Y}, title = {The Arabidopsis SMO2, a homologue of yeast TRM112, modulates progression of cell division during organ growth.}, journal = {The Plant journal : for cell and molecular biology}, volume = {61}, number = {4}, pages = {600-610}, doi = {10.1111/j.1365-313X.2009.04085.x}, pmid = {19929876}, issn = {1365-313X}, mesh = {Amino Acid Sequence ; Arabidopsis/*genetics/growth & development ; Arabidopsis Proteins/genetics/*metabolism ; *Cell Division ; Cell Proliferation ; Cloning, Molecular ; DNA, Plant/genetics ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Molecular Sequence Data ; Phylogeny ; Plant Leaves/genetics/*growth & development ; Plant Roots/genetics/*growth & development ; Plants, Genetically Modified/genetics ; Sequence Alignment ; }, abstract = {Cell proliferation is integrated into developmental progression in multicellular organisms, including plants, and the regulation of cell division is of pivotal importance for plant growth and development. Here, we report the identification of an Arabidopsis SMALL ORGAN 2 (SMO2) gene that functions in regulation of the progression of cell division during organ growth. The smo2 knockout mutant displays reduced size of aerial organs and shortened roots, due to the decreased number of cells in these organs. Further analyses reveal that disruption of SMO2 does not alter the developmental timing but reduces the rate of cell production during leaf and root growth. Moreover, smo2 plants exhibit a constitutive activation of cell cycle-related genes and over-accumulation of cells expressing CYCB1;1:beta-glucuronidase (CYCB1;1:GUS) during organogenesis, suggesting that smo2 has a defect in G(2)-M phase progression in the cell cycle. SMO2 encodes a functional homologue of yeast TRM112, a plurifunctional component involved in a few cellular events, including tRNA and protein methylation. In addition, the mutation of SMO2 does not appear to affect endoreduplication in Arabidopsis leaf cells. Taken together we postulate that Arabidopsis SMO2 is a conserved yeast TRM112 homologue and SMO2-mediated cellular events are required for proper progression of cell division in plant growth and development.}, } @article {pmid19920346, year = {2009}, author = {Niklas, KJ}, title = {Functional adaptation and phenotypic plasticity at the cellular and whole plant level.}, journal = {Journal of biosciences}, volume = {34}, number = {4}, pages = {613-620}, pmid = {19920346}, issn = {0973-7138}, mesh = {*Adaptation, Physiological ; Biological Evolution ; Cell Wall/physiology/ultrastructure ; *Environment ; Models, Biological ; *Phenotype ; *Plant Cells ; *Plant Physiological Phenomena ; Signal Transduction ; Stress, Physiological ; }, abstract = {The ability to adaptively alter morphological, anatomical, or physiological functional traits to local environmental variations using external environmental cues is especially well expressed by all terrestrial and most aquatic plants. A ubiquitous cue eliciting these plastic phenotypic responses is mechanical perturbation (MP), which can evoke dramatic differences in the size, shape, or mechanical properties of conspecifics. Current thinking posits that MP is part of a very ancient "stress-perception response system" that involves receptors located at the cell membrane/cell wall interface capable of responding to a broad spectrum of stress-inducing factors. This hypothesis is explored here from the perspective of cell wall evolution and the control of cell wall architecture by unicellular and multicellular plants. Among the conclusions that emerge from this exploration is the perspective that the plant cell is phenotypically plastic.}, } @article {pmid19920341, year = {2009}, author = {Newman, SA and Bhat, R and Mezentseva, NV}, title = {Cell state switching factors and dynamical patterning modules: complementary mediators of plasticity in development and evolution.}, journal = {Journal of biosciences}, volume = {34}, number = {4}, pages = {553-572}, pmid = {19920341}, issn = {0973-7138}, mesh = {*Adaptation, Biological ; Animals ; *Biological Evolution ; Body Patterning/genetics ; Cell Adhesion ; Cell Differentiation ; Cell Polarity ; Chick Embryo ; Embryonic Development/*genetics ; *Gene Expression Regulation, Developmental ; Gene Regulatory Networks/physiology ; Limb Buds/cytology/embryology ; Signal Transduction ; Transcription Factors/genetics/physiology ; }, abstract = {Ancient metazoan organisms arose from unicellular eukaryotes that had billions of years of genetic evolution behind them. The transcription factor networks present in single-celled ancestors at the origin of the Metazoa (multicellular animals) were already capable of mediating the switching of the unicellular phenotype among alternative states of gene activity in response to environmental conditions. Cell differentiation, therefore, had its roots in phenotypic plasticity, with the ancient regulatory proteins acquiring new targets over time and evolving into the "developmental transcription factors" (DTFs) of the "developmental-genetic toolkit." In contrast, the emergence of pattern formation and morphogenesis in the Metazoa had a different trajectory. Aggregation of unicellular metazoan ancestors changed the organisms' spatial scale, leading to the first "dynamical patterning module" (DPM): cell-cell adhesion. Following this, other DPMs (defined as physical forces and processes pertinent to the scale of the aggregates mobilized by a set of toolkit gene products distinct from the DTFs), transformed simple cell aggregates into hollow, multilayered, segmented, differentiated and additional complex structures, with minimal evolution of constituent genes. Like cell differentiation, therefore, metazoan morphologies also originated from plastic responses of cells and tissues. Here we describe examples of DTFs and most of the important DPMs, discussing their complementary roles in the evolution of developmental mechanisms. We also provide recently characterized examples of DTFs in cell type switching and DPMs in morphogenesis of avian limb bud mesenchyme, an embryo-derived tissue that retains a high degree of developmental plasticity.}, } @article {pmid19919722, year = {2009}, author = {Kordis, D and Turk, V}, title = {Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes.}, journal = {BMC evolutionary biology}, volume = {9}, number = {}, pages = {266}, pmid = {19919722}, issn = {1471-2148}, mesh = {Archaea/*genetics ; Bacteria/*genetics ; Cystatins/*genetics ; Cysteine Proteinase Inhibitors/genetics ; Eukaryota/*genetics ; Evolution, Molecular ; Gene Duplication ; Genomics ; *Phylogeny ; }, abstract = {BACKGROUND: The cystatin superfamily comprises cysteine protease inhibitors that play key regulatory roles in protein degradation processes. Although they have been the subject of many studies, little is known about their genesis, evolution and functional diversification. Our aim has been to obtain a comprehensive insight into their origin, distribution, diversity, evolution and classification in Eukaryota, Bacteria and Archaea.

RESULTS: We have identified in silico the full complement of the cystatin superfamily in more than 2100 prokaryotic and eukaryotic genomes. The analysis of numerous eukaryotic genomes has provided strong evidence for the emergence of this superfamily in the ancestor of eukaryotes. The progenitor of this superfamily was most probably intracellular and lacked a signal peptide and disulfide bridges, much like the extant Giardia cystatin. A primordial gene duplication produced two ancestral eukaryotic lineages, cystatins and stefins. While stefins remain encoded by a single or a small number of genes throughout the eukaryotes, the cystatins have undergone a more complex and dynamic evolution through numerous gene and domain duplications. In the cystatin superfamily we discovered twenty vertebrate-specific and three angiosperm-specific orthologous families, indicating that functional diversification has occurred only in multicellular eukaryotes. In vertebrate orthologous families, the prevailing trends were loss of the ancestral inhibitory activity and acquisition of novel functions in innate immunity. Bacterial cystatins and stefins may be emergency inhibitors that enable survival of bacteria in the host, defending them from the host's proteolytic activity.

CONCLUSION: This study challenges the current view on the classification, origin and evolution of the cystatin superfamily and provides valuable insights into their functional diversification. The findings of this comprehensive study provide guides for future structural and evolutionary studies of the cystatin superfamily as well as of other protease inhibitors and proteases.}, } @article {pmid19917305, year = {2010}, author = {Kupiec, JJ}, title = {On the lack of specificity of proteins and its consequences for a theory of biological organization.}, journal = {Progress in biophysics and molecular biology}, volume = {102}, number = {1}, pages = {45-52}, doi = {10.1016/j.pbiomolbio.2009.11.002}, pmid = {19917305}, issn = {1873-1732}, mesh = {Animals ; Humans ; *Models, Biological ; Proteins/genetics/*metabolism ; }, abstract = {It is now widely recognized that gene expression and cellular processes include a probabilistic component. However, this does not essentially modify the theory of genetic programming. This stochastic aspect, which is called noise, is usually conceived as a margin of fluctuation in the way the genetic program functions and the latter remains understood as a specific mechanism guided by genetic information. In contrast, recent data show that proteins do not possess a high level of specificity. They can interact with numerous molecular partners. As a consequence molecular interactions are not simply "noisy". Because they are subject to large combinatorial interaction possibilities, they are also intrinsically stochastic and must be sorted out by the cell structure. This contradicts the genetic programming theory which is based on the idea that protein interactions are directed by their stereospecificity and genetic information. Taking into account the lack of protein specificity leads to a new theory. Natural selection acts not only in evolution but also in ontogenesis by sorting stochastic molecular interactions. In this frame, the making up of an organism, instead of being a simple bottom-top process in which information flows from genes to phenotypes, is both a bottom-top and top-bottom process. Genes provide proteins, but their stochastic interactions are sorted by selective constraints arising from the cell and multi-cellular structures, which are themselves subject to the action of natural selection.}, } @article {pmid19898529, year = {2009}, author = {Lu, PY and Lévesque, N and Kobor, MS}, title = {NuA4 and SWR1-C: two chromatin-modifying complexes with overlapping functions and components.}, journal = {Biochemistry and cell biology = Biochimie et biologie cellulaire}, volume = {87}, number = {5}, pages = {799-815}, doi = {10.1139/O09-062}, pmid = {19898529}, issn = {1208-6002}, support = {MOP-79442//Canadian Institutes of Health Research/Canada ; }, mesh = {Adenosine Triphosphatases/metabolism/*physiology ; Animals ; Chromatin/*metabolism ; Eukaryotic Cells/metabolism/physiology ; Gene Regulatory Networks/physiology ; Histone Acetyltransferases/metabolism/*physiology ; Humans ; Models, Biological ; Multiprotein Complexes/metabolism/*physiology ; Phylogeny ; Saccharomyces cerevisiae/genetics/metabolism/physiology ; Saccharomyces cerevisiae Proteins/metabolism/*physiology ; }, abstract = {Chromatin structure is important for the compaction of eukaryotic genomes, thus chromatin modifications play a fundamental role in regulating many cellular processes. The coordinated activities of various chromatin-remodelling and -modifying complexes are crucial in maintaining distinct chromatin neighbourhoods, which in turn ensure appropriate gene expression, as well as DNA replication, repair, and recombination. SWR1-C is an ATP-dependent histone deposition complex for the histone variant H2A.Z, whereas NuA4 is a histone acetyltransferase for histones H4, H2A, and H2A.Z. Together the NuA4 and SWR1-C chromatin-modifying complexes alter the chromatin structure through 3 distinct modifications in yeast: post-translational addition of chemical groups, ATP-dependent chromatin remodelling, and histone variant incorporation. These 2 multi-protein complexes share 4 subunits and function together to regulate the circuitry of H2A.Z biology. The components and functions of both multi-protein complexes are evolutionarily conserved and play important roles in multi-cellular development and cellular differentiation in higher eukaryotes. This review will summarize recent findings about NuA4 and SWR1-C and will focus on the connection between these complexes by investigating their physical and functional interactions through eukaryotic evolution.}, } @article {pmid19895704, year = {2009}, author = {Liu, N and Xiao, ZD and Yu, CH and Shao, P and Liang, YT and Guan, DG and Yang, JH and Chen, CL and Qu, LH and Zhou, H}, title = {SnoRNAs from the filamentous fungus Neurospora crassa: structural, functional and evolutionary insights.}, journal = {BMC genomics}, volume = {10}, number = {}, pages = {515}, pmid = {19895704}, issn = {1471-2164}, mesh = {*Evolution, Molecular ; Gene Expression Regulation, Fungal ; Genome, Fungal/genetics ; Genomics ; Neurospora crassa/*genetics ; RNA, Fungal/classification/*genetics/*metabolism ; RNA, Small Nucleolar/classification/*genetics/*metabolism ; }, abstract = {BACKGROUND: SnoRNAs represent an excellent model for studying the structural and functional evolution of small non-coding RNAs involved in the post-transcriptional modification machinery for rRNAs and snRNAs in eukaryotic cells. Identification of snoRNAs from Neurospora crassa, an important model organism playing key roles in the development of modern genetics, biochemistry and molecular biology will provide insights into the evolution of snoRNA genes in the fungus kingdom.

RESULTS: Fifty five box C/D snoRNAs were identified and predicted to guide 71 2'-O-methylated sites including four sites on snRNAs and three sites on tRNAs. Additionally, twenty box H/ACA snoRNAs, which potentially guide 17 pseudouridylations on rRNAs, were also identified. Although not exhaustive, the study provides the first comprehensive list of two major families of snoRNAs from the filamentous fungus N. crassa. The independently transcribed strategy dominates in the expression of box H/ACA snoRNA genes, whereas most of the box C/D snoRNA genes are intron-encoded. This shows that different genomic organizations and expression modes have been adopted by the two major classes of snoRNA genes in N. crassa . Remarkably, five gene clusters represent an outstanding organization of box C/D snoRNA genes, which are well conserved among yeasts and multicellular fungi, implying their functional importance for the fungus cells. Interestingly, alternative splicing events were found in the expression of two polycistronic snoRNA gene hosts that resemble the UHG-like genes in mammals. Phylogenetic analysis further revealed that the extensive separation and recombination of two functional elements of snoRNA genes has occurred during fungus evolution.

CONCLUSION: This is the first genome-wide analysis of the filamentous fungus N. crassa snoRNAs that aids in understanding the differences between unicellular fungi and multicellular fungi. As compared with two yeasts, a more complex pattern of methylation guided by box C/D snoRNAs in multicellular fungus than in unicellular yeasts was revealed, indicating the high diversity of post-transcriptional modification guided by snoRNAs in the fungus kingdom.}, } @article {pmid19894587, year = {2009}, author = {Funayama, N}, title = {[Origin and evolution of stem cell system in multicellular animals].}, journal = {Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme}, volume = {54}, number = {14}, pages = {1856-1863}, pmid = {19894587}, issn = {0039-9450}, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation ; Hydra/cytology ; Multipotent Stem Cells/*cytology ; Planarians/cytology ; Porifera/*cytology/genetics ; }, } @article {pmid19890270, year = {2010}, author = {Raz, E}, title = {Mucosal immunity: aliment and ailments.}, journal = {Mucosal immunology}, volume = {3}, number = {1}, pages = {4-7}, doi = {10.1038/mi.2009.123}, pmid = {19890270}, issn = {1935-3456}, support = {AI068685/AI/NIAID NIH HHS/United States ; AI083328/AI/NIAID NIH HHS/United States ; DK35108/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*immunology ; Digestive System/*immunology ; Evolution, Molecular ; Humans ; Immunity, Innate ; *Immunity, Mucosal ; Inflammatory Bowel Diseases/immunology/microbiology/therapy ; Lymphopoiesis ; Mice ; Probiotics/therapeutic use ; Symbiosis ; }, abstract = {The development of the primitive gut in the multicellular aquatic eukaryote was driven by the insufficient absorption of nutrients from the oceanic soup. The anatomy of this evolving specialized system invited its colonization by environmental prokaryotes and resulted in the establishment of the intestinal microflora. Innate immunity had previously evolved in gutless organisms such as plants and was fully functional in the gut of invertebrates. On the other hand, adaptive immunity evolved in vertebrates, most probably because of some selective pressure such as the adaptation to a predatory lifestyle. Interestingly, this form of immunity was localized first in their primitive gut. Although the newly generated eukaryote-prokaryote relationship in the gut evolved under mutualistic principles, its symbiotic nature is easily interrupted by extrinsic factors such the composition of the consumed food. Thus, it is argued below that a state of disequilibrium with the microflora (dysbiosis) results in potentially serious immune-related disadvantages to the host.}, } @article {pmid19882309, year = {2010}, author = {Azad, P and Zhang, M and Woodruff, RC}, title = {Rapid increase in viability due to new beneficial mutations in Drosophila melanogaster.}, journal = {Genetica}, volume = {138}, number = {2}, pages = {251-263}, pmid = {19882309}, issn = {1573-6857}, mesh = {Animals ; Chromosomes/genetics ; Drosophila melanogaster/*genetics/*physiology ; Female ; Genome, Insect/genetics ; Heterozygote ; Homozygote ; Male ; *Mutation ; Survival Analysis ; Time Factors ; }, abstract = {It is usually assumed that new beneficial mutations are extremely rare. Yet, few experiments have been performed in multicellular organisms that measure the effect of new beneficial mutations on viability and other measures of fitness. In most experiments, it is difficult to clearly distinguish whether adaptations have occurred due to selection on new beneficial mutations or on preexisting genetic variation. Using a modification of a Dobzhansky and Spassky (Evolution 1:191-216, 1947) assay to study change in viability over generations, we have observed an increase in viability in lines homozygous for the second and third chromosomes of Drosophila melanogaster in 6-26 generations due to the occurrence of new beneficial mutations in population sizes of 20, 100 and 1,000. The lines with the lowest initial viability responded the fastest to new beneficial mutations. These results show that new beneficial mutations, along with selection, can quickly increase viability and fitness even in small populations. Hence, new advantageous mutations may play an important role in adaptive evolution in higher organisms.}, } @article {pmid19880309, year = {2009}, author = {Degnan, BM and Vervoort, M and Larroux, C and Richards, GS}, title = {Early evolution of metazoan transcription factors.}, journal = {Current opinion in genetics & development}, volume = {19}, number = {6}, pages = {591-599}, doi = {10.1016/j.gde.2009.09.008}, pmid = {19880309}, issn = {1879-0380}, mesh = {Animals ; *Evolution, Molecular ; Genomics ; Multigene Family ; Phylogeny ; Transcription Factors/*chemistry ; }, abstract = {Analyses of recently sequenced sponge, cnidarian, placozoan, and choanoflagellate genomes have revealed that most transcription factor (TF) classes and families expressed during bilaterian development originated at the dawn of the animal kingdom, before the divergence of contemporary animal lineages. The ancestral metazoan genome included members of the bHLH, Mef2, Fox, Sox, T-box, ETS, nuclear receptor, Rel/NF-kappaB, bZIP, and Smad families, and a diversity of homeobox-containing classes, including ANTP, Prd-like, Pax, POU, LIM-HD, Six, and TALE. As many of these TF classes and families appear to be metazoan specific and not present in choanoflagellates, fungi and more distant eukaryotes, their genesis and expansion may have contributed to the evolution of animal multicellularity.}, } @article {pmid19879146, year = {2009}, author = {Vos, M and Velicer, GJ}, title = {Social conflict in centimeter-and global-scale populations of the bacterium Myxococcus xanthus.}, journal = {Current biology : CB}, volume = {19}, number = {20}, pages = {1763-1767}, pmid = {19879146}, issn = {1879-0445}, support = {R01 GM079690-02/GM/NIGMS NIH HHS/United States ; GM07690/GM/NIGMS NIH HHS/United States ; R01 GM079690-01/GM/NIGMS NIH HHS/United States ; R01 GM079690-03/GM/NIGMS NIH HHS/United States ; R01 GM079690/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Typing Techniques ; Genetic Variation ; *Microbial Interactions ; Myxococcus xanthus/genetics/growth & development/*physiology ; Soil Microbiology ; Spores, Bacterial/genetics/physiology ; }, abstract = {Social interactions among microbes that engage in cooperative behaviors are well studied in laboratory contexts [1, 2], but little is known about the scales at which initially cooperative microbes diversify into socially conflicting genotypes in nature. The predatory soil bacterium Myxococcus xanthus responds to starvation by cooperatively forming multicellular fruiting bodies in which a portion of the population differentiates into stress-resistant spores [3, 4]. Natural M. xanthus populations are spatially structured [5], and genetically divergent isolates from distant origins exhibit striking developmental antagonisms that decrease spore production in chimeric fruiting bodies [6]. Here we show that genetically similar isolates of M. xanthus from a centimeter-scale population [7] also exhibit strong and pervasive antagonisms when mixed in development. Negative responses to chimerism were less intense on average among local strains than among global isolates, although no significant correlation was found between genetic distance at multilocus sequence typing (MLST) loci and the degree of social asymmetry between competitors. A test for self/nonself discrimination during vegetative swarming revealed a great diversity of distinct self-recognition types even among identical MLST genotypes. Such nonself exclusion may serve to direct the benefits of cooperation to close kin within diverse populations in which the probability of social conflict among neighbors is high.}, } @article {pmid19876739, year = {2010}, author = {Agnello, M and Roccheri, MC}, title = {Apoptosis: Focus on sea urchin development.}, journal = {Apoptosis : an international journal on programmed cell death}, volume = {15}, number = {3}, pages = {322-330}, doi = {10.1007/s10495-009-0420-0}, pmid = {19876739}, issn = {1573-675X}, mesh = {Animals ; *Apoptosis ; Evolution, Molecular ; Sea Urchins/*cytology/embryology/*growth & development ; }, abstract = {It has been proposed that the apoptosis is an essential requirement for the evolution of all animals, in fact the apoptotic program is highly conserved from nematodes to mammals. Throughout development, apoptosis is employed by multicellular organisms to eliminate damaged or unnecessary cells. Here, we will discuss both developmental programmed cell death (PCD) under normal conditions and stress induced apoptosis, in sea urchin embryos. Sea urchin represent an excellent model system for studying embryogenesis and cellular processes involved in metamorphosis. PCD plays an essential role in sculpting and remodelling the embryos and larvae undergoing metamorphosis. Moreover, this marine organism directly interacts with its environment, and is susceptible to effects of several aquatic contaminants. Apoptosis can be adopted as a defence mechanism against any environmental chemical, physical and mechanical stress, for removing irreversibly damaged cells. This review, while not comprehensive in its reporting, aims to provide an overview of current knowledge on mechanisms to regulate physiological and the induced apoptotic program in sea urchin embryos.}, } @article {pmid19863728, year = {2010}, author = {Niklas, KJ and Kutschera, U}, title = {The evolution of the land plant life cycle.}, journal = {The New phytologist}, volume = {185}, number = {1}, pages = {27-41}, doi = {10.1111/j.1469-8137.2009.03054.x}, pmid = {19863728}, issn = {1469-8137}, mesh = {*Biological Evolution ; Eukaryota/*genetics ; Gene Regulatory Networks ; Phylogeny ; *Plant Development ; Plant Structures ; Plants/embryology/*genetics ; Reproduction ; }, abstract = {The extant land plants are unique among the monophyletic clade of photosynthetic eukaryotes, which consists of the green algae (chlorophytes), the charophycean algae (charophytes), numerous groups of unicellular algae (prasinophytes) and the embryophytes, by possessing, firstly, a sexual life cycle characterized by an alternation between a haploid, gametophytic and a diploid, sporophytic multicellular generation; secondly, the formation of egg cells within multicellular structures called archegonia; and, thirdly, the retention of the zygote and diploid sporophyte embryo within the archegonium. We review the developmental, paleobotanical and molecular evidence indicating that: the embryophytes descended from a charophyte-like ancestor; this common ancestor had a life cycle with only a haploid multicellular generation; and the most ancient (c. 410 Myr old) land plants (e.g. Cooksonia, Rhynia and Zosterophyllum) had a dimorphic life cycle (i.e. their haploid and diploid generations were morphologically different). On the basis of these findings, we suggest that the multicellular reproductive structures of extant charophytes and embryophytes are developmentally homologous, and that those of the embryophytes evolved by virtue of the co-option and re-deployment of ancient algal homeodomain gene networks.}, } @article {pmid19862577, year = {2010}, author = {Baker, RE and Yates, CA and Erban, R}, title = {From microscopic to macroscopic descriptions of cell migration on growing domains.}, journal = {Bulletin of mathematical biology}, volume = {72}, number = {3}, pages = {719-762}, doi = {10.1007/s11538-009-9467-x}, pmid = {19862577}, issn = {1522-9602}, mesh = {Cell Movement/*physiology ; Computer Simulation ; *Models, Biological ; Signal Transduction ; *Stochastic Processes ; }, abstract = {Cell migration and growth are essential components of the development of multicellular organisms. The role of various cues in directing cell migration is widespread, in particular, the role of signals in the environment in the control of cell motility and directional guidance. In many cases, especially in developmental biology, growth of the domain also plays a large role in the distribution of cells and, in some cases, cell or signal distribution may actually drive domain growth. There is an almost ubiquitous use of partial differential equations (PDEs) for modelling the time evolution of cellular density and environmental cues. In the last 20 years, a lot of attention has been devoted to connecting macroscopic PDEs with more detailed microscopic models of cellular motility, including models of directional sensing and signal transduction pathways. However, domain growth is largely omitted in the literature. In this paper, individual-based models describing cell movement and domain growth are studied, and correspondence with a macroscopic-level PDE describing the evolution of cell density is demonstrated. The individual-based models are formulated in terms of random walkers on a lattice. Domain growth provides an extra mathematical challenge by making the lattice size variable over time. A reaction-diffusion master equation formalism is generalised to the case of growing lattices and used in the derivation of the macroscopic PDEs.}, } @article {pmid19852616, year = {2009}, author = {Wang, AD and Sharp, NP and Spencer, CC and Tedman-Aucoin, K and Agrawal, AF}, title = {Selection, epistasis, and parent-of-origin effects on deleterious mutations across environments in Drosophila melanogaster.}, journal = {The American naturalist}, volume = {174}, number = {6}, pages = {863-874}, doi = {10.1086/645088}, pmid = {19852616}, issn = {1537-5323}, mesh = {Animals ; Crosses, Genetic ; Drosophila melanogaster/*genetics/growth & development/physiology ; *Epistasis, Genetic ; Genotype ; Larva/genetics/physiology ; *Mutation ; *Selection, Genetic ; }, abstract = {Understanding the nature of selection against deleterious alleles is central to determining how populations are affected by the constant influx of new mutations. Important progress has been made in estimating basic attributes of the distribution of selection coefficients and gene interaction effects (epistasis). Although most aspects of selection are likely to be context dependent, little is known about the effect of stress on selection and epistasis at the level of individual genes, especially in multicellular organisms. Using Drosophila melanogaster, we measure how selection on 20 mutant alleles is affected by direct and indirect genetic factors across two environments. We find that environmental stress increases selection against individual mutations but reduces selection against combinations of mutations (i.e., epistasis becomes more positive). In addition, we find a high incidence of indirect genetic effects whereby the strength of selection against the alleles carried by offspring is dependent on the genotypes of their parents.}, } @article {pmid19850457, year = {2009}, author = {King, A and Gottlieb, E}, title = {Glucose metabolism and programmed cell death: an evolutionary and mechanistic perspective.}, journal = {Current opinion in cell biology}, volume = {21}, number = {6}, pages = {885-893}, doi = {10.1016/j.ceb.2009.09.009}, pmid = {19850457}, issn = {1879-0410}, mesh = {Animals ; Apoptosis/*physiology ; Autophagy/*physiology ; *Biological Evolution ; Cell Survival ; Glucose/*metabolism ; Humans ; Models, Biological ; Oxidative Stress ; Signal Transduction ; }, abstract = {Over the last decade, cellular glucose metabolism has emerged as a central player in the mechanisms of programmed cell death (PCD). We examined the metabolic foundations of apoptosis from a Darwinian context and suggest that PCD has evolved from the cellular response to metabolic stress, most notably in relation to glucose metabolism. Whilst apoptosis and other forms of PCD are essential to the development, maintenance and survival of multicellular organisms, it is now evident that controlled and selective cell death confers fitness advantages in unicellular organisms. All species may thus harbour a fundamental relationship between the availability of basic nutrients and life/death decisions. This evolutionary perspective may inform our understanding of PCD in its many guises.}, } @article {pmid19845633, year = {2009}, author = {Rustom, A}, title = {Hen or egg?: some thoughts on tunneling nanotubes.}, journal = {Annals of the New York Academy of Sciences}, volume = {1178}, number = {}, pages = {129-136}, doi = {10.1111/j.1749-6632.2009.04997.x}, pmid = {19845633}, issn = {1749-6632}, mesh = {Cell Communication/*physiology ; Gap Junctions/metabolism ; Ion Channels/*metabolism ; Models, Genetic ; Plasmodesmata/physiology ; Signal Transduction ; Synapses/metabolism ; }, abstract = {Precise coordination of various cell types and tissues represents a substantial prerequisite for the development and maintenance of multicellular organisms. Therefore, eukaryotic cells have developed a variety of complex structures, including synapses or gap junctions. Recently, thin membranous channels, termed "tunnelling nanotubes," were discovered. Tunnelling nanotubes interconnect miscellaneous animal cells and are assumed to be involved in important physiological and pathological mechanisms, such as the intercellular spread of diverse pathogens. This phenomenon shows striking similarities to plant tissues, where cells are connected via membranous channels, called plasmodesmata. Emerging evidence suggests that the discovery of tunnelling nanotubes may enforce reconsideration of previous conceptions of intercellular communication, additionally providing novel perspectives concerning early evolution of multicellular life-forms.}, } @article {pmid19845631, year = {2009}, author = {Baluska, F}, title = {Cell-cell channels, viruses, and evolution: via infection, parasitism, and symbiosis toward higher levels of biological complexity.}, journal = {Annals of the New York Academy of Sciences}, volume = {1178}, number = {}, pages = {106-119}, doi = {10.1111/j.1749-6632.2009.04995.x}, pmid = {19845631}, issn = {1749-6632}, mesh = {Cell Communication ; Cellular Structures/metabolism ; Eukaryotic Cells/cytology/metabolism ; *Evolution, Molecular ; Fungi/*pathogenicity ; Plants/*metabolism/parasitology ; Prokaryotic Cells/cytology/metabolism ; Signal Transduction ; Symbiosis/*physiology ; }, abstract = {Between prokaryotic cells and eukaryotic cells there is dramatic difference in complexity which represents a problem for the current version of the cell theory, as well as for the current version of evolution theory. In the past few decades, the serial endosymbiotic theory of Lynn Margulis has been confirmed. This results in a radical departure from our understanding of living systems: the eukaryotic cell represents de facto"cells-within-cell." Higher order "cells-within-cell" situations are obvious at the eukaryotic cell level in the form of secondary and tertiary endosymbiosis, or in the male and female gametophytes of higher plants. The next challenge of the current version of the cell theory is represented by the fact that the multicellular fungi and plants are, in fact, supracellular assemblies as their cells are not physically separated from each other. Moreover, there are also examples of alliances and mergings between multicellular organisms. Infection, especially the viral one, but also bacterial and fungal infections, followed by symbiosis, is proposed to act as the major force that drives the biological evolution toward higher complexity.}, } @article {pmid19845628, year = {2009}, author = {Forterre, P and Prangishvili, D}, title = {The great billion-year war between ribosome- and capsid-encoding organisms (cells and viruses) as the major source of evolutionary novelties.}, journal = {Annals of the New York Academy of Sciences}, volume = {1178}, number = {}, pages = {65-77}, doi = {10.1111/j.1749-6632.2009.04993.x}, pmid = {19845628}, issn = {1749-6632}, mesh = {Animals ; Capsid/*metabolism ; DNA, Viral/genetics ; *Evolution, Molecular ; Genes, Viral ; *Genome, Viral ; Humans ; Phenotype ; RNA, Messenger/metabolism ; RNA, Viral/genetics ; Viruses/*genetics/metabolism ; }, abstract = {Our conceptions on the origin, nature, and role of viruses have been shaken recently by several independent lines of research. There are many reasons to believe now that viruses are more ancient than modern cells and have always been more abundant and diverse than their cellular targets. Viruses can be defined as capsid-encoding organisms that transform their "host" cell into a viral factory. If capsid-encoding organisms (viruses) and ribosome-encoding organisms (cells) are the major types of living entities on our planet, it seems logical to conclude that their conflict has been a major engine of biological evolution (in the framework of natural selection). In particular, many novelties first selected in the viral world might have been transferred to cells as a consequence of the continuous flow of viral genes into cellular genomes. We discuss recent observations and hypotheses suggesting that viruses have played a major role at different stages of biological evolution, such as the RNA to DNA transition, the origin of the eukaryotic nucleus, or, alternatively, the origin of unique features in multicellular macrobes.}, } @article {pmid19843152, year = {2010}, author = {Kawakami, A}, title = {Stem cell system in tissue regeneration in fish.}, journal = {Development, growth & differentiation}, volume = {52}, number = {1}, pages = {77-87}, doi = {10.1111/j.1440-169X.2009.01138.x}, pmid = {19843152}, issn = {1440-169X}, mesh = {Animals ; Cell Differentiation ; Cell Proliferation ; Extremities/anatomy & histology/physiology ; Fishes/anatomy & histology/*physiology ; Models, Biological ; *Regeneration ; Stem Cells/*cytology ; }, abstract = {During evolution from single-cell to multi-cellular organisms, organisms developed the needed machinery by which a vast number of functionally different types of cells could be unified into an individual. To attain this goal, organisms evolved the developmental strategies that produced different cell types and unified them into complex body architecture. However, a more intriguing feature of multi-cellular organisms is that they can maintain their bodies throughout long life. For tissue maintenance, stem and/or progenitor cells in many tissues and organs are thought to play an important role; however, we know little about their control and the process of tissue reconstitution. As cells are fragile, all animals have the ability, more or less, to replace damaged or dead cells; however, there are large variations in such abilities, depending on the type of organs and the species. Though vertebrates cannot reconstitute their bodies from a small piece as do planarians, some lower vertebrates, unlike mammals, have the ability to regenerate body appendages and many internal organs. If we unveil the nature of stem cells in striking examples of such regeneration, this information can be applied to mammals and greatly benefit us. The focus in the present review is on the recent advances in our knowledge about the regeneration mechanism in fish, including the stem cells that are involved.}, } @article {pmid19833446, year = {2010}, author = {Parris, GE}, title = {Developmental diseases and the hypothetical Master Development Program.}, journal = {Medical hypotheses}, volume = {74}, number = {3}, pages = {564-573}, doi = {10.1016/j.mehy.2009.09.035}, pmid = {19833446}, issn = {1532-2777}, mesh = {Child ; Developmental Disabilities/*genetics ; Genetic Predisposition to Disease/*genetics ; Humans ; Infant ; Infant, Newborn ; *Models, Genetic ; Polymorphism, Single Nucleotide/*genetics ; Transcription Factors/*genetics ; }, abstract = {Small deletions and duplications frequently occur in the pericentromeric region of chromosomes and many of these are associated with developmental abnormalities. These developmental syndromes are conventionally attributed to abnormal expression of protein-coding genes in the affected region. A hypothesis has recently been published concerning a Master Development Program based on noncoding transcripts from these regions (Parris GE. A hypothetical Master Development Program for multi-cellular organisms: Ontogeny and phylogeny. Biosci Hypotheses 2009;2:3-12.). This paper summarizes and expands the recently published hypothesis to include it application to developmental diseases. The author proposes that development of multi-cellular organisms is guided by a Master Development Program (MDP) located primarily in the pericentromeric heterochromatin. The MDP is believed to consist of a series of Generation-Specific Control Keys (GSCK) transcribed in sequence by Ikaros family transcription factors unless the GSCKs are suppressed by Sall1-family or Dnmt3b-family proteins. The MDP is proposed to increment with each cell cycle to the next GSCK resulting in development of the clone. A clone may be programmed to split into two clones as necessary through a two-cycle mitosis processes. The transcripts of the GSCKs presumably yield noncoding nuclear messenger RNAs (nmRNAs, 8-30 nt units) that act directly (e.g., as primers for RNA polymerase II) and indirectly to regulate HOX and other high-level transcription factor and developmental genes. As envisioned, the MDP would evolve by terminal addition of new GSCKs. The new GSCKs are produced by evolutionary consolidation of retro-transcripts into pyknons that collect and evolve at the end of the pericentromeric heterochromatin and are eventually incorporated into the MDP. The retro-transcripts are though to be produced during episodic retrovirus epidemics and account for punctuated equilibrium in species evolution.}, } @article {pmid19828049, year = {2009}, author = {Foret, S and Kucharski, R and Pittelkow, Y and Lockett, GA and Maleszka, R}, title = {Epigenetic regulation of the honey bee transcriptome: unravelling the nature of methylated genes.}, journal = {BMC genomics}, volume = {10}, number = {}, pages = {472}, pmid = {19828049}, issn = {1471-2164}, mesh = {Animals ; Bees/*genetics ; Computational Biology ; CpG Islands ; *DNA Methylation ; *Epigenesis, Genetic ; *Gene Expression Profiling ; Gene Expression Regulation ; Genes, Insect ; Genome, Insect ; Oligonucleotide Array Sequence Analysis ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Epigenetic modification of DNA via methylation is one of the key inventions in eukaryotic evolution. It provides a source for the switching of gene activities, the maintenance of stable phenotypes and the integration of environmental and genomic signals. Although this process is widespread among eukaryotes, both the patterns of methylation and their relevant biological roles not only vary noticeably in different lineages, but often are poorly understood. In addition, the evolutionary origins of DNA methylation in multicellular organisms remain enigmatic. Here we used a new 'epigenetic' model, the social honey bee Apis mellifera, to gain insights into the significance of methylated genes.

RESULTS: We combined microarray profiling of several tissues with genome-scale bioinformatics and bisulfite sequencing of selected genes to study the honey bee methylome. We find that around 35% of the annotated honey bee genes are expected to be methylated at the CpG dinucleotides by a highly conserved DNA methylation system. We show that one unifying feature of the methylated genes in this species is their broad pattern of expression and the associated 'housekeeping' roles. In contrast, genes involved in more stringently regulated spatial or temporal functions are predicted to be un-methylated.

CONCLUSION: Our data suggest that honey bees use CpG methylation of intragenic regions as an epigenetic mechanism to control the levels of activity of the genes that are broadly expressed and might be needed for conserved core biological processes in virtually every type of cell. We discuss the implications of our findings for genome-scale regulatory network structures and the evolution of the role(s) of DNA methylation in eukaryotes. Our findings are particularly important in the context of the emerging evidence that environmental factors can influence the epigenetic settings of some genes and lead to serious metabolic and behavioural disorders.}, } @article {pmid19825834, year = {2009}, author = {Swaminathan, S and Morrone, D and Wang, Q and Fulton, DB and Peters, RJ}, title = {CYP76M7 is an ent-cassadiene C11alpha-hydroxylase defining a second multifunctional diterpenoid biosynthetic gene cluster in rice.}, journal = {The Plant cell}, volume = {21}, number = {10}, pages = {3315-3325}, pmid = {19825834}, issn = {1532-298X}, mesh = {Animals ; Cell Line ; Cytochrome P-450 Enzyme System/genetics/*metabolism ; Diterpenes/*metabolism ; Gas Chromatography-Mass Spectrometry ; Kinetics ; Magnetic Resonance Spectroscopy ; Molecular Sequence Data ; Multigene Family/*genetics ; Oryza/genetics/*metabolism ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Spodoptera ; }, abstract = {Biosynthetic gene clusters are common in microbial organisms, but rare in plants, raising questions regarding the evolutionary forces that drive their assembly in multicellular eukaryotes. Here, we characterize the biochemical function of a rice (Oryza sativa) cytochrome P450 monooxygenase, CYP76M7, which seems to act in the production of antifungal phytocassanes and defines a second diterpenoid biosynthetic gene cluster in rice. This cluster is uniquely multifunctional, containing enzymatic genes involved in the production of two distinct sets of phytoalexins, the antifungal phytocassanes and antibacterial oryzalides/oryzadiones, with the corresponding genes being subject to distinct transcriptional regulation. The lack of uniform coregulation of the genes within this multifunctional cluster suggests that this was not a primary driving force in its assembly. However, the cluster is dedicated to specialized metabolism, as all genes in the cluster are involved in phytoalexin metabolism. We hypothesize that this dedication to specialized metabolism led to the assembly of the corresponding biosynthetic gene cluster. Consistent with this hypothesis, molecular phylogenetic comparison demonstrates that the two rice diterpenoid biosynthetic gene clusters have undergone independent elaboration to their present-day forms, indicating continued evolutionary pressure for coclustering of enzymatic genes encoding components of related biosynthetic pathways.}, } @article {pmid19825590, year = {2008}, author = {Buschmann, H and Lloyd, CW}, title = {Arabidopsis mutants and the network of microtubule-associated functions.}, journal = {Molecular plant}, volume = {1}, number = {6}, pages = {888-898}, doi = {10.1093/mp/ssn060}, pmid = {19825590}, issn = {1674-2052}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Arabidopsis/cytology/*genetics/*metabolism ; Arabidopsis Proteins/metabolism ; Genome, Plant/genetics ; Microtubules/genetics/*metabolism ; Mutation/*genetics ; }, abstract = {In early eukaryotes, the microtubule system was engaged in mitosis, intracellular transport, and flagellum-based motility. In the plant lineage, the evolution of a multicellular body involved the conservation of some core functions, the loss of others, and the elaboration of new microtubule functions associated with the multicellular plant habit. This diversification is reflected by the presence of both conserved (animal/fungi-like) and novel (plant-like) sequences encoding microtubule-related functions in the Arabidopsis genome. The collection of microtubule mutants has grown rapidly over recent years. These mutants present a wide range of phenotypes, consistent with the hypothesis of a functional diversification of the microtubule system. In this review, we focus on mutant analysis and, in particular, discuss double mutant analysis as a valuable tool for pinpointing pathways of gene function. A future challenge will be to define the complete network of genetic and physical interactions of microtubule function in plants. In addition to reviewing recent progress in the functional analysis of the 'MAPome', we present an online database of Arabidopsis mutants impaired in microtubule functions.}, } @article {pmid19812067, year = {2009}, author = {Takahashi, N and Hashino, M and Kami, C and Imaichi, R}, title = {Developmental morphology of strap-shaped gametophytes of Colysis decurrens: a new look at meristem development and function in fern gametophytes.}, journal = {Annals of botany}, volume = {104}, number = {7}, pages = {1353-1361}, pmid = {19812067}, issn = {1095-8290}, mesh = {Biological Evolution ; Germ Cells, Plant/*growth & development ; Meristem/*growth & development ; Polypodiaceae/*growth & development ; }, abstract = {BACKGROUND AND AIMS: The gametophytes of most homosporous ferns are cordate-thalloid in shape. Some are strap- or ribbon-shaped and have been assumed to have evolved from terrestrial cordate shapes as an adaptation to epiphytic habitats. The aim of the present study was to clarify the morphological evolution of the strap-shaped gametophyte of microsoroids (Polypodiaceae) by precise analysis of their development.

METHODS: Spores of Colysis decurrens collected in Kagoshima, Japan, were cultured and observed microscopically. Epi-illuminated micrographs of growing gametophytes were captured every 24 h, allowing analysis of the cell lineage of meristems. Light microscopy of resin-sections and scanning electron microscopy were also used.

KEY RESULTS: Contrary to previous assumptions that strap-shaped Colysis gametophytes have no organized meristem, three different types of meristems are formed during development: (1) apical-cell based - responsible for early growth; (2) marginal - further growth, including gametophyte branching; and (3) multicellular - formation of cushions with archegonia. The cushion is two or three layers thick and intermittent. The apical-cell and multicellular meristems are similar to those of cordate gametophytes of other ferns, but the marginal meristem is unique to the strap-shaped gametophyte of this fern.

CONCLUSIONS: The strap-shaped gametophytes of C. decurrens may have evolved from ancestors with a cordate shape by insertion of the marginal meristem phase between the first apical-cell-based meristem and subsequent multicellular meristem phases. Repeated retrieval of the marginal meristem at the multicellular meristem phase would result in indefinite prolongation of gametophyte growth, an ecological adaptation to epiphytic habitats.}, } @article {pmid19805427, year = {2009}, author = {Boomsma, JJ}, title = {Lifetime monogamy and the evolution of eusociality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {364}, number = {1533}, pages = {3191-3207}, pmid = {19805427}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Hymenoptera/*genetics ; *Selection, Genetic ; *Sexual Behavior, Animal ; *Social Behavior ; }, abstract = {All evidence currently available indicates that obligatory sterile eusocial castes only arose via the association of lifetime monogamous parents and offspring. This is consistent with Hamilton's rule (br(s) > r(o)c), but implies that relatedness cancels out of the equation because average relatedness to siblings (r(s)) and offspring (r(o)) are both predictably 0.5. This equality implies that any infinitesimally small benefit of helping at the maternal nest (b), relative to the cost in personal reproduction (c) that persists throughout the lifespan of entire cohorts of helpers suffices to establish permanent eusociality, so that group benefits can increase gradually during, but mostly after the transition. The monogamy window can be conceptualized as a singularity comparable with the single zygote commitment of gametes in eukaryotes. The increase of colony size in ants, bees, wasps and termites is thus analogous to the evolution of multicellularity. Focusing on lifetime monogamy as a universal precondition for the evolution of obligate eusociality simplifies the theory and may help to resolve controversies about levels of selection and targets of adaptation. The monogamy window underlines that cooperative breeding and eusociality are different domains of social evolution, characterized by different sectors of parameter space for Hamilton's rule.}, } @article {pmid19805080, year = {2009}, author = {Johnston, DT and Wolfe-Simon, F and Pearson, A and Knoll, AH}, title = {Anoxygenic photosynthesis modulated Proterozoic oxygen and sustained Earth's middle age.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {106}, number = {40}, pages = {16925-16929}, pmid = {19805080}, issn = {1091-6490}, mesh = {Anaerobiosis ; Atmosphere/chemistry ; Carbon Dioxide/chemistry ; Cyanobacteria/growth & development/physiology/radiation effects ; *Earth, Planet ; Iron/chemistry ; Light ; Models, Biological ; Nitrogen Fixation ; Oceans and Seas ; Oxidation-Reduction ; Oxygen/*chemistry ; Photosynthesis/*physiology/radiation effects ; Seawater/*chemistry ; Sulfides/chemistry ; }, abstract = {Molecular oxygen (O(2)) began to accumulate in the atmosphere and surface ocean ca. 2,400 million years ago (Ma), but the persistent oxygenation of water masses throughout the oceans developed much later, perhaps beginning as recently as 580-550 Ma. For much of the intervening interval, moderately oxic surface waters lay above an oxygen minimum zone (OMZ) that tended toward euxinia (anoxic and sulfidic). Here we illustrate how contributions to primary production by anoxygenic photoautotrophs (including physiologically versatile cyanobacteria) influenced biogeochemical cycling during Earth's middle age, helping to perpetuate our planet's intermediate redox state by tempering O(2) production. Specifically, the ability to generate organic matter (OM) using sulfide as an electron donor enabled a positive biogeochemical feedback that sustained euxinia in the OMZ. On a geologic time scale, pyrite precipitation and burial governed a second feedback that moderated sulfide availability and water column oxygenation. Thus, we argue that the proportional contribution of anoxygenic photosynthesis to overall primary production would have influenced oceanic redox and the Proterozoic O(2) budget. Later Neoproterozoic collapse of widespread euxinia and a concomitant return to ferruginous (anoxic and Fe(2+) rich) subsurface waters set in motion Earth's transition from its prokaryote-dominated middle age, removing a physiological barrier to eukaryotic diversification (sulfide) and establishing, for the first time in Earth's history, complete dominance of oxygenic photosynthesis in the oceans. This paved the way for the further oxygenation of the oceans and atmosphere and, ultimately, the evolution of complex multicellular organisms.}, } @article {pmid19799621, year = {2010}, author = {Vopálenská, I and St'ovícek, V and Janderová, B and Váchová, L and Palková, Z}, title = {Role of distinct dimorphic transitions in territory colonizing and formation of yeast colony architecture.}, journal = {Environmental microbiology}, volume = {12}, number = {1}, pages = {264-277}, doi = {10.1111/j.1462-2920.2009.02067.x}, pmid = {19799621}, issn = {1462-2920}, support = {55005623//Howard Hughes Medical Institute/United States ; }, mesh = {Ammonia/*metabolism ; Culture Media ; Gene Deletion ; Gene Expression Regulation, Fungal ; Hyphae/genetics/*growth & development/metabolism ; Membrane Glycoproteins/genetics/*metabolism ; Mutation ; Saccharomyces cerevisiae/genetics/*growth & development/metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; }, abstract = {Microbial populations in nature often form organized multicellular structures (biofilms, colonies) occupying different surfaces including host tissues and medical devices. How yeast cells within such populations cooperate and how their dimorphic switch to filamentous growth is regulated are therefore important questions. Studying population development, we discovered that Saccharomyces cerevisiae microcolonies early after their origination from one cell successfully occupy the territory via dimorphic transition, which is induced by ammonia and other volatile amines independently on cell ploidy and nutrients. It results in oriented pseudohyphal cell expansion in the direction of ammonia source, which consequently leads to unification of adjacent microcolonies to one more numerous entity. The further population development is accompanied by another dimorphic switch, which is strictly dependent on Flo11p adhesin and is indispensable for proper formation of biofilm-like aerial 3-D colony architecture. In this, Flo11p is required for both elongation of cells organized to radial clusters (formed earlier within the colony) and their subsequent pseudohyphal expansion. Just before this expansion, Flo11p relocalizes from the bud-neck of radial cell clusters also to the tip of elongated cells.}, } @article {pmid19792170, year = {2009}, author = {Pershin, YV and La Fontaine, S and Di Ventra, M}, title = {Memristive model of amoeba learning.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {80}, number = {2 Pt 1}, pages = {021926}, doi = {10.1103/PhysRevE.80.021926}, pmid = {19792170}, issn = {1539-3755}, mesh = {Amoeba/*physiology ; Animals ; Electric Conductivity ; Intelligence ; *Memory ; *Models, Neurological ; Physarum polycephalum/physiology ; }, abstract = {Recently, it was shown that the amoebalike cell Physarum polycephalum when exposed to a pattern of periodic environmental changes learns and adapts its behavior in anticipation of the next stimulus to come. Here we show that such behavior can be mapped into the response of a simple electronic circuit consisting of a LC contour and a memory-resistor (a memristor) to a train of voltage pulses that mimic environment changes. We also identify a possible biological origin of the memristive behavior in the cell. These biological memory features are likely to occur in other unicellular as well as multicellular organisms, albeit in different forms. Therefore, the above memristive circuit model, which has learning properties, is useful to better understand the origins of primitive intelligence.}, } @article {pmid19788731, year = {2009}, author = {Bapteste, E and O'Malley, MA and Beiko, RG and Ereshefsky, M and Gogarten, JP and Franklin-Hall, L and Lapointe, FJ and Dupré, J and Dagan, T and Boucher, Y and Martin, W}, title = {Prokaryotic evolution and the tree of life are two different things.}, journal = {Biology direct}, volume = {4}, number = {}, pages = {34}, pmid = {19788731}, issn = {1745-6150}, mesh = {*Biological Evolution ; Classification ; Models, Biological ; Phylogeny ; Prokaryotic Cells/*physiology ; }, abstract = {BACKGROUND: The concept of a tree of life is prevalent in the evolutionary literature. It stems from attempting to obtain a grand unified natural system that reflects a recurrent process of species and lineage splittings for all forms of life. Traditionally, the discipline of systematics operates in a similar hierarchy of bifurcating (sometimes multifurcating) categories. The assumption of a universal tree of life hinges upon the process of evolution being tree-like throughout all forms of life and all of biological time. In multicellular eukaryotes, the molecular mechanisms and species-level population genetics of variation do indeed mainly cause a tree-like structure over time. In prokaryotes, they do not. Prokaryotic evolution and the tree of life are two different things, and we need to treat them as such, rather than extrapolating from macroscopic life to prokaryotes. In the following we will consider this circumstance from philosophical, scientific, and epistemological perspectives, surmising that phylogeny opted for a single model as a holdover from the Modern Synthesis of evolution.

RESULTS: It was far easier to envision and defend the concept of a universal tree of life before we had data from genomes. But the belief that prokaryotes are related by such a tree has now become stronger than the data to support it. The monistic concept of a single universal tree of life appears, in the face of genome data, increasingly obsolete. This traditional model to describe evolution is no longer the most scientifically productive position to hold, because of the plurality of evolutionary patterns and mechanisms involved. Forcing a single bifurcating scheme onto prokaryotic evolution disregards the non-tree-like nature of natural variation among prokaryotes and accounts for only a minority of observations from genomes.

CONCLUSION: Prokaryotic evolution and the tree of life are two different things. Hence we will briefly set out alternative models to the tree of life to study their evolution. Ultimately, the plurality of evolutionary patterns and mechanisms involved, such as the discontinuity of the process of evolution across the prokaryote-eukaryote divide, summons forth a pluralistic approach to studying evolution.

REVIEWERS: This article was reviewed by Ford Doolittle, John Logsdon and Nicolas Galtier.}, } @article {pmid19770272, year = {2009}, author = {Maizels, RM and Pearce, EJ and Artis, D and Yazdanbakhsh, M and Wynn, TA}, title = {Regulation of pathogenesis and immunity in helminth infections.}, journal = {The Journal of experimental medicine}, volume = {206}, number = {10}, pages = {2059-2066}, pmid = {19770272}, issn = {1540-9538}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Autoimmunity ; B-Lymphocytes/immunology ; Helminthiasis/*immunology ; *Host-Parasite Interactions ; Humans ; Intercellular Signaling Peptides and Proteins/physiology ; Interleukin-17/immunology ; Interleukin-4/immunology ; Macrophage Activation ; T-Lymphocytes, Regulatory/immunology ; Th2 Cells/immunology ; }, abstract = {Helminths are multicellular eukaryotic parasites that infect over one quarter of the world's population. Through coevolution with the human immune system, these organisms have learned to exploit immunoregulatory pathways, resulting in asymptomatic tolerance of infections in many individuals. When infections and the resulting immune responses become dysregulated, however, acute and chronic pathologies often develop. A recent international meeting focused on how these parasites modulate host immunity and how control of parasitic and immunopathological disease might be achieved.}, } @article {pmid19761866, year = {2009}, author = {Watanabe, H and Hoang, VT and Mättner, R and Holstein, TW}, title = {Immortality and the base of multicellular life: Lessons from cnidarian stem cells.}, journal = {Seminars in cell & developmental biology}, volume = {20}, number = {9}, pages = {1114-1125}, doi = {10.1016/j.semcdb.2009.09.008}, pmid = {19761866}, issn = {1096-3634}, mesh = {Animals ; Body Patterning ; Cell Differentiation ; Cell Nucleus/metabolism ; Cnidaria/genetics/*physiology ; Developmental Biology/methods ; Hydra/physiology ; Models, Biological ; Phylogeny ; Plants/metabolism ; Regeneration ; Reproduction ; Signal Transduction ; Stem Cells/cytology ; }, abstract = {Cnidarians are phylogenetically basal members of the animal kingdom (>600 million years old). Together with plants they share some remarkable features that cannot be found in higher animals. Cnidarians and plants exhibit an almost unlimited regeneration capacity and immortality. Immortality can be ascribed to the asexual mode of reproduction that requires cells with an unlimited self-renewal capacity. We propose that the basic properties of animal stem cells are tightly linked to this archaic mode of reproduction. The cnidarian stem cells can give rise to a number of differentiated cell types including neuronal and germ cells. The genomes of Hydra and Nematostella, representatives of two major cnidarian classes indicate a surprising complexity of both genomes, which is in the range of vertebrates. Recent work indicates that highly conserved signalling pathways control Hydra stem cell differentiation. Furthermore, the availability of genomic resources and novel technologies provide approaches to analyse these cells in vivo. Studies of stem cells in cnidarians will therefore open important insights into the basic mechanisms of stem cell biology. Their critical phylogenetic position at the base of the metazoan branch in the tree of life makes them an important link in unravelling the common mechanisms of stem cell biology between animals and plants.}, } @article {pmid19761779, year = {2010}, author = {Rossetti, V and Schirrmeister, BE and Bernasconi, MV and Bagheri, HC}, title = {The evolutionary path to terminal differentiation and division of labor in cyanobacteria.}, journal = {Journal of theoretical biology}, volume = {262}, number = {1}, pages = {23-34}, doi = {10.1016/j.jtbi.2009.09.009}, pmid = {19761779}, issn = {1095-8541}, mesh = {Cell Communication/physiology ; Cell Compartmentation/genetics/*physiology ; Cell Division/genetics/physiology ; Cyanobacteria/*cytology/genetics/*growth & development/physiology ; *Evolution, Molecular ; Genetic Speciation ; Models, Biological ; Models, Theoretical ; Mutation/physiology ; Nitrogen Fixation/genetics/physiology ; Photoperiod ; Phylogeny ; Time Factors ; }, abstract = {A common trait often associated with multicellularity is cellular differentiation, which is a spatial separation of tasks through the division of labor. In principle, the division of labor does not necessarily have to be constrained to a multicellular setting. In this study, we focus on the possible evolutionary paths leading to terminal differentiation in cyanobacteria. We develop mathematical models for two developmental strategies. First, of populations of terminally differentiated single cells surviving by the exchange of common goods. Second, of populations exhibiting terminal differentiation in a multicellular setting. After testing the two strategies against the effect of disruptive mutations (i.e. "cheater" mutants), we assess the effects of selection on the optimization of the ratio of vegetative (carbon fixing) to heterocystous (nitrogen fixing) cells, which in turn leads to the maximization of the carrying capacity for the population density. In addition, we compare the performance of differentiated populations to undifferentiated ones that temporally separate tasks in accordance to a day/night cycle. We then compare some predictions of our model with phylogenetic relationships derived from analyzing 16S rRNA sequences of different cyanobacterial strains. In line with studies indicating that group or spatial structure are ways to evolve cooperation and protect against the spread of cheaters, our work shows that compartmentalization afforded by multicellularity is required to maintain the vegetative/heterocyst division in cyanobacteria. We find that multicellularity allows for selection to optimize the carrying capacity. These results and the phylogenetic analysis indicates that terminally differentiated cyanobacteria evolved after undifferentiated species. In addition, we show that, in regimes of short daylight periods, terminally differentiated species perform worse than undifferentiated species that follow the day/night cycle; indicating that undifferentiated species have an evolutionary advantage in regimes of short daylight periods.}, } @article {pmid19741707, year = {2009}, author = {Frei, R and Gaucher, C and Poulton, SW and Canfield, DE}, title = {Fluctuations in Precambrian atmospheric oxygenation recorded by chromium isotopes.}, journal = {Nature}, volume = {461}, number = {7261}, pages = {250-253}, pmid = {19741707}, issn = {1476-4687}, mesh = {Animals ; Atmosphere/*chemistry ; Biodiversity ; Chromium/*analysis/chemistry ; Chromium Isotopes ; History, Ancient ; Iron/analysis/metabolism ; Manganese Compounds/metabolism ; Oceans and Seas ; Oxidation-Reduction ; Oxides/metabolism ; Oxygen/analysis/*metabolism ; Seawater/chemistry ; }, abstract = {Geochemical data suggest that oxygenation of the Earth's atmosphere occurred in two broad steps. The first rise in atmospheric oxygen is thought to have occurred between approximately 2.45 and 2.2 Gyr ago, leading to a significant increase in atmospheric oxygen concentrations and concomitant oxygenation of the shallow surface ocean. The second increase in atmospheric oxygen appears to have taken place in distinct stages during the late Neoproterozoic era (approximately 800-542 Myr ago), ultimately leading to oxygenation of the deep ocean approximately 580 Myr ago, but details of the evolution of atmospheric oxygenation remain uncertain. Here we use chromium (Cr) stable isotopes from banded iron formations (BIFs) to track the presence of Cr(VI) in Precambrian oceans, providing a time-resolved picture of the oxygenation history of the Earth's atmosphere-hydrosphere system. The geochemical behaviour of Cr is highly sensitive to the redox state of the surface environment because oxidative weathering processes produce the oxidized hexavalent [Cr(VI)] form. Oxidation of reduced trivalent [Cr(III)] chromium on land is accompanied by an isotopic fractionation, leading to enrichment of the mobile hexavalent form in the heavier isotope. Our fractionated Cr isotope data indicate the accumulation of Cr(VI) in ocean surface waters approximately 2.8 to 2.6 Gyr ago and a likely transient elevation in atmospheric and surface ocean oxygenation before the first great rise of oxygen 2.45-2.2 Gyr ago (the Great Oxidation Event). In approximately 1.88-Gyr-old BIFs we find that Cr isotopes are not fractionated, indicating a decline in atmospheric oxygen. Our findings suggest that the Great Oxidation Event did not lead to a unidirectional stepwise increase in atmospheric oxygen. In the late Neoproterozoic, we observe strong positive fractionations in Cr isotopes (delta(53)Cr up to +4.9 per thousand), providing independent support for increased surface oxygenation at that time, which may have stimulated rapid evolution of macroscopic multicellular life.}, } @article {pmid19738200, year = {2009}, author = {Ernst, A and Sazinsky, SL and Hui, S and Currell, B and Dharsee, M and Seshagiri, S and Bader, GD and Sidhu, SS}, title = {Rapid evolution of functional complexity in a domain family.}, journal = {Science signaling}, volume = {2}, number = {87}, pages = {ra50}, doi = {10.1126/scisignal.2000416}, pmid = {19738200}, issn = {1937-9145}, mesh = {Adaptor Proteins, Signal Transducing/*chemistry/*genetics ; Animals ; Binding Sites/genetics ; *Directed Molecular Evolution ; Humans ; Ligands ; Mutagenesis ; Protein Structure, Tertiary ; }, abstract = {Multicellular organisms rely on complex, fine-tuned protein networks to respond to environmental changes. We used in vitro evolution to explore the role of domain mutation and expansion in the evolution of network complexity. Using random mutagenesis to facilitate family expansion, we asked how versatile and robust the binding site must be to produce the rich functional diversity of the natural PDZ domain family. From a combinatorial protein library, we analyzed several hundred structured domain variants and found that one-quarter were functional for carboxyl-terminal ligand recognition and that our variant repertoire was as specific and diverse as the natural family. Our results show that ligand binding is hardwired in the PDZ fold and suggest that this flexibility may facilitate the rapid evolution of complex protein interaction networks.}, } @article {pmid19732154, year = {2009}, author = {Beninati, T and Riegler, M and Vilcins, IM and Sacchi, L and McFadyen, R and Krockenberger, M and Bandi, C and O'Neill, SL and Lo, N}, title = {Absence of the symbiont Candidatus Midichloria mitochondrii in the mitochondria of the tick Ixodes holocyclus.}, journal = {FEMS microbiology letters}, volume = {299}, number = {2}, pages = {241-247}, doi = {10.1111/j.1574-6968.2009.01757.x}, pmid = {19732154}, issn = {1574-6968}, mesh = {Alphaproteobacteria/*isolation & purification/*physiology ; Animals ; Australia ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Female ; Humans ; Ixodes/*microbiology/*physiology ; Male ; Microscopy, Electron, Transmission ; Mitochondria/*microbiology ; Molecular Sequence Data ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Symbiosis ; }, abstract = {Candidatus Midichloria mitochondrii (M. mitochondrii) belongs to a novel clade of bacteria within the order Rickettsiales. Recent PCR-based screening studies indicate that it is present in a number of blood-sucking arthropods, as well as the blood of some vertebrates. Its medical and veterinary significance remains to be determined. Electron microscopic examinations of M. mitochondrii have thus far been conducted on two infected tick species. Remarkably, the bacterium was found in abundance within the mitochondria of the ovarian cells of each tick species. This makes it the only characterized bacterium able to invade the mitochondria of any multicellular organism. To examine whether mitochondrial invasion is a consistent characteristic of M. mitochondrii, we examined two tick species found in Eastern Australia. One of these species, Ixodes holocyclus, was infected with two M. mitochondrii strains; however, no bacteria were seen in the mitochondria. Comparative studies involving these strains may shed light on the unique phenomenon of mitochondrial invasion.}, } @article {pmid19731212, year = {2009}, author = {Hoenigsberg, HF and Sanabria, C}, title = {A genomic parasite in the evolution of metazoan development.}, journal = {Genetics and molecular research : GMR}, volume = {8}, number = {3}, pages = {896-914}, doi = {10.4238/vol8-3gmr571}, pmid = {19731212}, issn = {1676-5680}, mesh = {Adaptation, Physiological/genetics ; Animals ; *Biological Evolution ; Cell Lineage ; DNA, Intergenic/genetics ; Genome/*genetics ; Growth and Development/*genetics ; Immune System/cytology ; Inheritance Patterns/genetics ; Models, Genetic ; Parasites/*genetics ; Signal Transduction/genetics ; }, abstract = {It is a challenge to understand how development emerged as a mechanism to dismantle and dismiss the intromission of foreign parasites in order to consolidate a higher-level multicellular unit of selection where more heritable variations in fitness, required for complex organization, can be procured. Levels in biological hierarchy genes, networks of genes, chromosomes, cells, organisms, etc., possess heritable variations in fitness to varying degrees, and as such, they function as units of selection in the evolutionary process [Lewontin, (1970). The units of selection. Annu. Rev. Ecol. Syst. 1: 1-18]. To proceed from each of these levels to the next constitutes a major transition in evolutionary history. When analyzing the splendid road epitomized by these transitions in units of selection, it is possible to conceive three processes: firstly, the molecular "recognition" of the "convenience" of exchanging the higher energy cost of cooperating cells with more fitness than single-cell selection (after that first recognition the emergence of cooperation among cells is possible); secondly, the establishment of the mechanisms to regulate conflict, and finally, the regulation of cell differentiation and compartmentalization.}, } @article {pmid19725820, year = {2009}, author = {Dickinson, HG and Grant-Downton, R}, title = {Bridging the generation gap: flowering plant gametophytes and animal germlines reveal unexpected similarities.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {84}, number = {4}, pages = {589-615}, doi = {10.1111/j.1469-185X.2009.00088.x}, pmid = {19725820}, issn = {1469-185X}, support = {BB/F007558/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/F008694/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Epigenesis, Genetic ; Gene Expression Profiling ; Magnoliopsida/*genetics ; Phylogeny ; }, abstract = {Alternation of generations underpins all plant life histories and is held to possess important adaptive features. A wide range of data have accumulated over the past century which suggest that alternation from sporophyte to gametophyte in angiosperms includes a significant phase of 'informational reprogramming', leaving the founder cells of the gametophyte developmentally uncommitted. This review attempts to bring together results from these historic studies with more recent data on molecular and epigenetic events which accompany alternation, gametophyte development and gametogenesis in angiosperms. It is striking that most members of the other principal group of multicellular eukaryotes--the animals--have a completely different a life history: animals generate their gametes directly from diploid germlines, often set aside early in development. Nevertheless, a comparison between animal germlines and angiosperm gametophyte development reveals a number of surprising similarities at the cytological and molecular levels. This difference in life history but similarity in developmental process is reviewed in the context of the very different life strategies adopted by plants and animals, and particularly the fact that plants do not set aside diploid germlines early in development.}, } @article {pmid19722108, year = {2010}, author = {Ivaska, J and Heino, J}, title = {Interplay between cell adhesion and growth factor receptors: from the plasma membrane to the endosomes.}, journal = {Cell and tissue research}, volume = {339}, number = {1}, pages = {111-120}, pmid = {19722108}, issn = {1432-0878}, support = {202809/ERC_/European Research Council/International ; }, mesh = {Animals ; Cell Adhesion/physiology ; Cell Membrane/*metabolism ; Endosomes/*metabolism ; Humans ; Integrins/*metabolism ; Receptors, Growth Factor/*metabolism ; }, abstract = {The emergence of multicellular animals could only take place once evolution had produced molecular mechanisms for cell adhesion and communication. Today, all metazoans express integrin-type adhesion receptors and receptors for growth factors. Integrins recognize extracellular matrix proteins and respective receptors on other cells and, following ligand binding, can activate the same cellular signaling pathways that are regulated by growth factor receptors. Recent reports have indicated that the two receptor systems also collaborate in many other ways. Here, we review the present information concerning the role of integrins as assisting growth factor receptors and the interplay between the receptors in cell signaling and in the orchestration of receptor recycling.}, } @article {pmid19721894, year = {2009}, author = {Herron, MD}, title = {Many from one: Lessons from the volvocine algae on the evolution of multicellularity.}, journal = {Communicative & integrative biology}, volume = {2}, number = {4}, pages = {368-370}, pmid = {19721894}, issn = {1942-0889}, abstract = {The volvocine green algae are a model system for the evolution of multicellularity and cellular differentiation. A combination of molecular genetic and phylogenetic comparative approaches has resulted in a detailed picture of the transition from single cells to differentiated, multicellular organisms in this group. To be useful as a model system, the volvocine algae should provide information that is relevant to other groups. Here I discuss recent advances in understanding the origins of multicellularity and cellular differentiation in the volvocine algae and consider the implications for such transitions in general. Several general principles emerge that are relevant to the origins of major multicellular groups, such as animals, plants, fungi, red and brown algae. First, if the lessons learned from the volvocine algae can be generalized to other origins of multicellularity, we should expect these transitions to be understandable as a series of small changes, each potentially adaptive in itself. In addition, cooperation, conflict and mediation of conflicts among cells are likely to have played central roles. Finally, we should expect the histories of these transitions to include parallel evolution of some traits, periods of relatively rapid change interspersed with long periods of stasis, and simpler forms coexisting with more complex forms for long periods of time as in the evolution of the volvocine algae.}, } @article {pmid19720646, year = {2009}, author = {Arendt, D and Hausen, H and Purschke, G}, title = {The 'division of labour' model of eye evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {364}, number = {1531}, pages = {2809-2817}, pmid = {19720646}, issn = {1471-2970}, mesh = {Animals ; *Evolution, Molecular ; Eye Proteins/genetics ; Light Signal Transduction/*genetics ; Ocular Physiological Phenomena/*genetics ; Photoreceptor Cells/*physiology ; }, abstract = {The 'division of labour' model of eye evolution is elaborated here. We propose that the evolution of complex, multicellular animal eyes started from a single, multi-functional cell type that existed in metazoan ancestors. This ancient cell type had at least three functions: light detection via a photoreceptive organelle, light shading by means of pigment granules and steering through locomotor cilia. Located around the circumference of swimming ciliated zooplankton larvae, these ancient cells were able to mediate phototaxis in the absence of a nervous system. This precursor then diversified, by cell-type functional segregation, into sister cell types that specialized in different subfunctions, evolving into separate photoreceptor cells, shading pigment cells (SPCs) or ciliated locomotor cells. Photoreceptor sensory cells and ciliated locomotor cells remained interconnected by newly evolving axons, giving rise to an early axonal circuit. In some evolutionary lines, residual functions prevailed in the specialized cell types that mirror the ancient multi-functionality, for instance, SPCs expressing an opsin as well as possessing rhabdomer-like microvilli, vestigial cilia and an axon. Functional segregation of cell types in eye evolution also explains the emergence of more elaborate photosensory-motor axonal circuits, with interneurons relaying the visual information.}, } @article {pmid19717742, year = {2009}, author = {Godoy, PD and Nogueira-Junior, LA and Paes, LS and Cornejo, A and Martins, RM and Silber, AM and Schenkman, S and Elias, MC}, title = {Trypanosome prereplication machinery contains a single functional orc1/cdc6 protein, which is typical of archaea.}, journal = {Eukaryotic cell}, volume = {8}, number = {10}, pages = {1592-1603}, pmid = {19717742}, issn = {1535-9786}, mesh = {Amino Acid Sequence ; Archaea/*genetics/metabolism ; Archaeal Proteins/*genetics/metabolism ; Cell Cycle Proteins/genetics/metabolism ; *DNA Replication ; Molecular Sequence Data ; Origin Recognition Complex/*genetics/metabolism ; Protozoan Proteins/*genetics/metabolism ; RNA Interference ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; }, abstract = {In unicellular eukaryotes, such as Saccharomyces cerevisiae, and in multicellular organisms, the replication origin is recognized by the heterohexamer origin recognition complex (ORC) containing six proteins, Orc1 to Orc6, while in members of the domain Archaea, the replication origin is recognized by just one protein, Orc1/Cdc6; the sequence of Orc1/Cdc6 is highly related to those of Orc1 and Cdc6. Similar to Archaea, trypanosomatid genomes contain only one gene encoding a protein named Orc1. Since trypanosome Orc1 is also homologous to Cdc6, in this study we named the Orc1 protein from trypanosomes Orc1/Cdc6. Here we show that the recombinant Orc1/Cdc6 from Trypanosoma cruzi (TcOrc1/Cdc6) and from Trypanosoma brucei (TbOrc1/Cdc6) present ATPase activity, typical of prereplication machinery components. Also, TcOrc1/Cdc6 and TbOrc1/Cdc6 replaced yeast Cdc6 but not Orc1 in a phenotypic complementation assay. The induction of Orc1/Cdc6 silencing by RNA interference in T. brucei resulted in enucleated cells, strongly suggesting the involvement of Orc1/Cdc6 in DNA replication. Orc1/Cdc6 is expressed during the entire cell cycle in the nuclei of trypanosomes, remaining associated with chromatin in all stages of the cell cycle. These results allowed us to conclude that Orc1/Cdc6 is indeed a member of the trypanosome prereplication machinery and point out that trypanosomes carry a prereplication machinery that is less complex than other eukaryotes and closer to archaea.}, } @article {pmid19713749, year = {2009}, author = {Collins, LJ and Chen, XS}, title = {Ancestral RNA: the RNA biology of the eukaryotic ancestor.}, journal = {RNA biology}, volume = {6}, number = {5}, pages = {495-502}, doi = {10.4161/rna.6.5.9551}, pmid = {19713749}, issn = {1555-8584}, mesh = {Epigenesis, Genetic ; *Eukaryota ; *Evolution, Molecular ; RNA/genetics ; RNA, Untranslated/*genetics ; Regulatory Sequences, Ribonucleic Acid ; }, abstract = {Our knowledge of RNA biology within eukaryotes has exploded over the last five years. Within new research we see that some features that were once thought to be part of multicellular life have now been identified in several protist lineages. Hence, it is timely to ask which features of eukaryote RNA biology are ancestral to all eukaryotes. We focus on RNA-based regulation and epigenetic mechanisms that use small regulatory ncRNAs and long ncRNAs, to highlight some of the many questions surrounding eukaryotic ncRNA evolution.}, } @article {pmid19713240, year = {2009}, author = {Barak, JD and Gorski, L and Liang, AS and Narm, KE}, title = {Previously uncharacterized Salmonella enterica genes required for swarming play a role in seedling colonization.}, journal = {Microbiology (Reading, England)}, volume = {155}, number = {Pt 11}, pages = {3701-3709}, doi = {10.1099/mic.0.032029-0}, pmid = {19713240}, issn = {1465-2080}, mesh = {Bacterial Proteins/*genetics ; Biofilms/growth & development ; Genes, Bacterial ; Hydrolases/*genetics ; Medicago sativa/microbiology ; Mutation ; Periplasmic Proteins/*genetics ; Phylogeny ; Salmonella enterica/*genetics/growth & development ; Seedlings/*microbiology ; }, abstract = {Incidences of bacterial foodborne illness caused by ingestion of fresh produce are rising. Instead of this being due to incidental contamination, the animal pathogen Salmonella enterica utilizes specific molecular mechanisms to attach to and colonize plants. This work characterizes two S. enterica genes of unknown function: a putative periplasmic protein, STM0278, and a putative protein with a hydrolase in the C-terminus, STM0650. STM0278 and STM0650 are important for seedling colonization but appear to have different roles during the process of colonization. Mutants of either STM0278 or STM0650 showed reduced colonization of alfalfa seedlings at 24 h, and the STM0278 mutant also showed reduced colonization at 48 h. Both genes were expressed in planta at 4 h following inoculation of 3-day-old seedlings and at 72 h after seed inoculation. This suggests that the role of STM0650 in seedling colonization is less important later in the process or is duplicated by other mechanisms. Mutants of STM0278 and STM0650 were defective in swarming. The STM0278 mutant failed to swarm in 24 h, while swarming of the STM0650 mutant was delayed. Addition of surfactant restored swarming of the STM0278 mutant, suggesting that STM0278 is involved in surfactant or osmotic agent production or deployment. Alfalfa seed exudates as the sole nutrient source were capable of perpetuating S. enterica swarming. Sequence analysis revealed sequences homologous to STM0278 and STM0650 in plant-associated bacteria, but none in Escherichia coli. Phylogenetic analysis of STM0650 showed similar sequences from diverse classes of plant-associated bacteria. Bacteria that preferentially colonize roots, including S. enterica, may use a similar hydrolase for swarming or biofilm production on plants. Multicellular behaviours by S. enterica appear central to plant colonization. S. enterica genes involved in plant colonization and survival outside of a host are most likely among the 'function unknown' genes of this bacterium.}, } @article {pmid19707546, year = {2009}, author = {Shadwick, LL and Spiegel, FW and Shadwick, JD and Brown, MW and Silberman, JD}, title = {Eumycetozoa = Amoebozoa?: SSUrDNA phylogeny of protosteloid slime molds and its significance for the amoebozoan supergroup.}, journal = {PloS one}, volume = {4}, number = {8}, pages = {e6754}, pmid = {19707546}, issn = {1932-6203}, mesh = {Animals ; DNA, Ribosomal/*genetics ; Likelihood Functions ; Mycetozoa/classification/*genetics ; *Phylogeny ; Polymerase Chain Reaction ; }, abstract = {Amoebae that make fruiting bodies consisting of a stalk and spores and classified as closely related to the myxogastrids have classically been placed in the taxon Eumycetozoa. Traditionally, there are three groups comprising Eumycetozoa: myxogastrids, dictyostelids, and the so-called protostelids. Dictyostelids and myxogastrids both make multicellular fruiting bodies that may contain hundreds of spores. Protostelids are those amoebae that make simple fruiting bodies consisting of a stalk and one or a few spores. Protostelid-like organisms have been suggested as the progenitors of the myxogastrids and dictyostelids, and they have been used to formulate hypotheses on the evolution of fruiting within the group. Molecular phylogenies have been published for both myxogastrids and dictyostelids, but little molecular phylogenetic work has been done on the protostelids. Here we provide phylogenetic trees based on the small subunit ribosomal RNA gene (SSU) that include 21 protostelids along with publicly available sequences from a wide variety of amoebae and other eukaryotes. SSU trees recover seven well supported clades that contain protostelids but do not appear to be specifically related to one another and are often interspersed among established groups of amoebae that have never been reported to fruit. In fact, we show that at least two taxa unambiguously belong to amoebozoan lineages where fruiting has never been reported. These analyses indicate that we can reject a monophyletic Eumycetozoa, s.l. For this reason, we will hereafter refer to those slime molds with simple fruiting as protosteloid amoebae and/or protosteloid slime molds, not as protostelids. These results add to our understanding of amoebozoan biodiversity, and demonstrate that the paradigms for understanding both nonfruiting and sporulating amoebae must be integrated. Finally, we suggest strategies for future research on protosteloid amoebae and nonfruiting amoebae, and discuss the impact of this work for taxonomists and phylogenomicists.}, } @article {pmid19692665, year = {2009}, author = {Brown, MW and Spiegel, FW and Silberman, JD}, title = {Phylogeny of the "forgotten" cellular slime mold, Fonticula alba, reveals a key evolutionary branch within Opisthokonta.}, journal = {Molecular biology and evolution}, volume = {26}, number = {12}, pages = {2699-2709}, doi = {10.1093/molbev/msp185}, pmid = {19692665}, issn = {1537-1719}, mesh = {Animals ; Bayes Theorem ; Bias ; Dictyosteliida/*classification/cytology/*genetics/growth & development ; *Evolution, Molecular ; Life Cycle Stages/genetics ; Likelihood Functions ; Multigene Family/genetics ; *Phylogeny ; RNA, Ribosomal/genetics ; Ribosome Subunits, Small, Eukaryotic/genetics ; }, abstract = {The shared ancestry between Fungi and animals has been unequivocally demonstrated by abundant molecular and morphological data for well over a decade. Along with the animals and Fungi, multiple protists have been placed in the supergroup Opisthokonta making it exceptionally diverse. In an effort to place the cellular slime mold Fonticula alba, an amoeboid protist with aggregative, multicellular fruiting, we sequenced five nuclear encoded genes; small subunit ribosomal RNA, actin, beta-tubulin, elongation factor 1-alpha, and the cytosolic isoform of heat shock protein 70 for phylogenetic analyses. Molecular trees demonstrate that Fonticula is an opisthokont that branches sister to filose amoebae in the genus Nuclearia. Fonticula plus Nuclearia are sister to Fungi. We propose a new name for this well-supported clade, Nucletmycea, incorporating Nuclearia, Fonticula, and Fungi. Fonticula represents the first example of a cellular slime mold morphology within Opisthokonta. Thus, there are four types of multicellularity in the supergroup-animal, fungal, colonial, and now aggregative. Our data indicate that multicellularity in Fonticula evolved independent of that found in the fungal and animal radiations. With the rapidly expanding sequence and genomic data becoming available from many opisthokont lineages, Fonticula may be fundamental to understanding opisthokont evolution as well as any possible commonalities involved with the evolution of multicellularity.}, } @article {pmid19692404, year = {2009}, author = {Aikawa, T and Anbutsu, H and Nikoh, N and Kikuchi, T and Shibata, F and Fukatsu, T}, title = {Longicorn beetle that vectors pinewood nematode carries many Wolbachia genes on an autosome.}, journal = {Proceedings. Biological sciences}, volume = {276}, number = {1674}, pages = {3791-3798}, pmid = {19692404}, issn = {0962-8452}, mesh = {Animals ; Coleoptera/*microbiology/*parasitology ; Female ; Genes, Bacterial ; Genome, Insect ; Male ; Nematoda/*physiology ; Phylogeny ; Wolbachia/*genetics ; }, abstract = {Monochamus alternatus is the longicorn beetle notorious as a vector of the pinewood nematode that causes the pine wilt disease. When two populations of M. alternatus were subjected to diagnostic polymerase chain reaction (PCR) detection of four Wolbachia genes, only the ftsZ gene was detected from one of the populations. The Wolbachia ftsZ gene persisted even after larvae were fed with a tetracycline-containing diet for six weeks. The inheritance of the ftsZ gene was not maternal but biparental, exhibiting a typical Mendelian pattern. The ftsZ gene titres in homozygotic ftsZ(+) insects were nearly twice as high as those in heterozygotic ftsZ(+) insects. Exhaustive PCR surveys revealed that 31 and 30 of 214 Wolbachia genes examined were detected from the two insect populations, respectively. Many of these Wolbachia genes contained stop codon(s) and/or frame shift(s). Fluorescent in situ hybridization confirmed the location of the Wolbachia genes on an autosome. On the basis of these results, we conclude that a large Wolbachia genomic region has been transferred to and located on an autosome of M. alternatus. The discovery of massive gene transfer from Wolbachia to M. alternatus would provide further insights into the evolution and fate of laterally transferred endosymbiont genes in multicellular host organisms.}, } @article {pmid19688285, year = {2009}, author = {Flegr, J}, title = {A possible role of intracellular isoelectric focusing in the evolution of eukaryotic cells and multicellular organisms.}, journal = {Journal of molecular evolution}, volume = {69}, number = {5}, pages = {444-451}, pmid = {19688285}, issn = {1432-1432}, mesh = {Animals ; *Biological Evolution ; Cell Physiological Phenomena ; Cytoplasm/physiology ; *Eukaryotic Cells/cytology/physiology ; Hydrogen-Ion Concentration ; *Isoelectric Focusing ; Models, Biological ; Proteins/physiology ; }, abstract = {A new scenario of the origin of eukaryotic cell and multicellularity is presented. A concentric pH-gradient has been shown to exist in the cytosol of eukaryotic cells. The most probable source of such gradient is its self-formation in gradient of electric field between center and periphery of a cell. Theoretical analysis has shown that, for example, a cell of Saccharomyces cerevisiae has enough energy to continuously sustain such gradient of strength about 1.5 kV/cm, the value sufficient for effective isoelectric focusing of cytoplasmic proteins. Focusing of enzymes could highly increase the effectiveness of an otherwise diffusion-limited metabolism of large cells by concentrating enzymes into small and distinct parts of a cytoplasm. By taking away an important physical constraint to the volume of cytoplasm, the intracellular isoelectric focusing enabled evolution of cells 3-4 order of magnitude larger than typical prokaryotic cells. This opened the way for the origin of phagocytosis and lately for the development of different forms of endosymbiosis, some of them resulting in an endosymbiotic origin of mitochondria and plastids. The large volume of a cell-enabled separation of nuclear and cytoplasmic compartments which was a precondition for separation of transcription and translation processes and therefore also for the origin of various RNA-preprocessing mechanisms. The possibility to regulate gene expression by postprocessing RNA and to regulate metabolism by an electrophoretic translocation enzymes between different parts of cytoplasm by changing their isoelectric points opened the way for cell and tissue differentiation and therefore for the origin of complex multicellular organisms.}, } @article {pmid19686678, year = {2009}, author = {Martindale, MQ and Hejnol, A}, title = {A developmental perspective: changes in the position of the blastopore during bilaterian evolution.}, journal = {Developmental cell}, volume = {17}, number = {2}, pages = {162-174}, doi = {10.1016/j.devcel.2009.07.024}, pmid = {19686678}, issn = {1878-1551}, mesh = {Animals ; *Biological Evolution ; *Body Patterning ; Cell Lineage ; Cell Polarity ; *Embryo, Nonmammalian/anatomy & histology/physiology ; Gastrula/*metabolism ; Gastrulation ; Phylogeny ; }, abstract = {Progress in resolving the phylogenetic relationships among animals and the expansion of molecular developmental studies to a broader variety of organisms has provided important insights into the evolution of developmental programs. These new studies make it possible to reevaluate old hypotheses about the evolution of animal body plans and to elaborate new ones. Here, we review recent studies that shed light on the transition from a radially organized ancestor to the last common ancestor of the Bilateria ("Urbilaterian") and present an integrative hypothesis about plausible developmental scenarios for the evolution of complex multicellular animals.}, } @article {pmid19667126, year = {2009}, author = {Zaidel-Bar, R}, title = {Evolution of complexity in the integrin adhesome.}, journal = {The Journal of cell biology}, volume = {186}, number = {3}, pages = {317-321}, pmid = {19667126}, issn = {1540-8140}, support = {F32 GM078747/GM/NIGMS NIH HHS/United States ; R01 GM058038/GM/NIGMS NIH HHS/United States ; GM058038-09/GM/NIGMS NIH HHS/United States ; GM078747-01/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Adhesion/physiology ; Humans ; Integrins/*metabolism ; }, abstract = {Integrin-mediated adhesion is as ancient as multicellularity, but it was not always as complex as it is in humans. Here, I examine the extent of conservation of 192 adhesome proteins across the genomes of nine model organisms spanning one and a half billion years of evolution. The work reveals that Rho GTPases, lipid- and serine/threonine-kinases, and phosphatases existed before integrins, but tyrosine phosphorylation developed concomitant with integrins. The expansion of specific functional groups such as GAPs, GEFs, adaptors, and receptors is demonstrated, along with the expansion of specific protein domains, such as SH3, PH, SH2, CH, and LIM. Expansion is due to gene duplication and creation of families of paralogues. Apparently, these paralogues share few partners and create new sets of interactions, thus increasing specificity and the repertoire of integrin-mediated signaling. Interestingly, the average number of interactions positively correlates with the evolutionary age of proteins. While shedding light on the evolution of adhesome complexity, this analysis also highlights the relevance and creates a framework for studying integrin-mediated adhesion in simpler model organisms.}, } @article {pmid19665850, year = {2010}, author = {Kozlov, AP}, title = {The possible evolutionary role of tumors in the origin of new cell types.}, journal = {Medical hypotheses}, volume = {74}, number = {1}, pages = {177-185}, doi = {10.1016/j.mehy.2009.07.027}, pmid = {19665850}, issn = {1532-2777}, mesh = {Animals ; Biological Evolution ; Cell Differentiation ; Cell Line, Tumor ; Humans ; Mice ; Models, Biological ; Models, Genetic ; Neoplasms/*genetics/*pathology ; Rhizobium/metabolism ; }, abstract = {The ability of tumor cells to differentiate in combination with their ability to express genes that are not expressed in normal tissues, may result in the emergence of new cell types in evolution. Tumors may play an evolutionary role by providing conditions (space and resources) for the expression of newly evolving genes. Genetically or epigenetically predetermined tumors at the early stages of progression, benign tumors, and some tumor-like processes in invertebrates and plants, all of which are modes of excess cell growth which provide evolving multicellular organisms with extra cell masses, are considered as potentially evolutionarily meaningful. Malignant tumors at the late stages of progression, however, are not. The preexisting cell types of multicellular organisms had restricted potential for the expression of newly evolving genes. Because of regulation and gene competition, some of the newly evolving genes may stay silent. Multicellular organisms would need excess cell masses for the expression of newly evolving genes. The preexisting cell types cannot provide such excess cell masses because of limitations imposed on the number of possible cell divisions. Tumors could provide the evolving multicellular organisms with the excess cell masses for the expression of newly evolving genes. We suggest that tumors could be a sort of proving ground (or reservoir) for the expression of newly evolving genes that originate in the course of genome evolution in the DNA of germ cells (i.e., not in tumor cells themselves). The case in which the expression of a newly evolving gene in tumors results in the origin of a new function would be associated with the origin of new feedback and regulatory circuits, as in root nodules in legumes and macromelanophores in Xiphophorus fishes. Tumor cells would differentiate, resulting in a new cell type for the given multicellular species. This cell type would be inherited because of epigenomic mechanisms similar to those in preexisting cell types. Populations of tumor-bearing organisms with genetically or epigenetically programmed tumors could represent the transition between established species of organisms at different stages of progressive evolution. Experimental confirmation of the prediction of the hypothesis of evolution by tumor cells differentiation concerning the expression of evolutionarily new genes and/or silent (neutrally evolving) sequences in tumor cells is presented.}, } @article {pmid19648465, year = {2009}, author = {Fernàndez-Busquets, X and Körnig, A and Bucior, I and Burger, MM and Anselmetti, D}, title = {Self-recognition and Ca2+-dependent carbohydrate-carbohydrate cell adhesion provide clues to the cambrian explosion.}, journal = {Molecular biology and evolution}, volume = {26}, number = {11}, pages = {2551-2561}, doi = {10.1093/molbev/msp170}, pmid = {19648465}, issn = {1537-1719}, mesh = {Animals ; *Biological Evolution ; Calcium/*metabolism ; Carbohydrates/*chemistry ; Cell Adhesion/physiology ; Models, Biological ; Molecular Structure ; }, abstract = {The Cambrian explosion of life was a relatively short period approximately 540 Ma that marked a generalized acceleration in the evolution of most animal phyla, but the trigger of this key biological event remains elusive. Sponges are the oldest extant Precambrian metazoan phylum and thus a valid model to study factors that could have unleashed the rise of multicellular animals. One such factor is the advent of self-/non-self-recognition systems, which would be evolutionarily beneficial to organisms to prevent germ-cell parasitism or the introduction of deleterious mutations resulting from fusion with genetically different individuals. However, the molecules responsible for allorecognition probably evolved gradually before the Cambrian period, and some other (external) factor remains to be identified as the missing triggering event. Sponge cells associate through calcium-dependent, multivalent carbohydrate-carbohydrate interactions of the g200 glycan found on extracellular proteoglycans. Single molecule force spectroscopy analysis of g200-g200 binding indicates that calcium affects the lifetime (+Ca/-Ca: 680 s/3 s) and bond reaction length (+Ca/-Ca: 3.47 A/2.27 A). Calculation of mean g200 dissociation times in low and high calcium within the theoretical framework of a cooperative binding model indicates the nonlinear and divergent characteristics leading to either disaggregated cells or stable multicellular assemblies, respectively. This fundamental phenomenon can explain a switch from weak to strong adhesion between primitive metazoan cells caused by the well-documented rise in ocean calcium levels at the end of Precambrian time. We propose that stronger cell adhesion allowed the integrity of genetically uniform animals composed only of "self" cells, facilitating genetic constitutions to remain within the metazoan individual and be passed down inheritance lines. The Cambrian explosion might have been triggered by the coincidence in time of primitive animals endowed with self-/non-self-recognition and of a surge in seawater calcium that increased the binding forces between their calcium-dependent cell adhesion molecules.}, } @article {pmid19641026, year = {2009}, author = {Kianianmomeni, A and Stehfest, K and Nematollahi, G and Hegemann, P and Hallmann, A}, title = {Channelrhodopsins of Volvox carteri are photochromic proteins that are specifically expressed in somatic cells under control of light, temperature, and the sex inducer.}, journal = {Plant physiology}, volume = {151}, number = {1}, pages = {347-366}, pmid = {19641026}, issn = {0032-0889}, mesh = {Amino Acid Sequence ; Gene Expression Regulation, Plant/*physiology ; Light ; Molecular Sequence Data ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Protein Conformation ; RNA, Messenger/genetics/metabolism ; Reproduction/physiology ; Stress, Physiological ; Temperature ; Volvox/*cytology/genetics/*metabolism ; }, abstract = {Channelrhodopsins are light-gated ion channels involved in the photoresponses of microalgae. Here, we describe the characterization of two channelrhodopsins, Volvox channelrhodopsin-1 (VChR1) and VChR2, from the multicellular green alga Volvox carteri. Both are encoded by nuclear single copy genes and are highly expressed in the small biflagellated somatic cells but not in the asexual reproductive cells (gonidia). Expression of both VChRs increases after cell cleavage and peaks after completion of embryogenesis, when the biosynthesis of the extracellular matrix begins. Likewise, expression of both transcripts increases after addition of the sex-inducer protein, but VChR2 is induced much more than VChR1. The expression of VChR1 is specifically promoted by extended dark periods, and heat stress reduces predominantly VChR1 expression. Expression of both VChRs increased under low light conditions, whereas cold stress and wounding reduced expression. Both VChRs were spectroscopically studied in their purified recombinant forms. VChR2 is similar to the ChR2 counterpart from Chlamydomonas reinhardtii with respect to its absorption maximum (460 nm) and photocycle dynamics. In contrast, VChR1 absorbs maximally at 540 nm at low pH (D540), shifting to 500 nm at high pH (D500). Flash photolysis experiments showed that after light excitation, the D540 dark state bleaches and at least two photoproducts, P600 and P500, are sequentially populated during the photocycle. We hypothesize that VChR2 is a general photoreceptor that is responsible for the avoidance of blue light and might play a key role in sexual development, whereas VChR1 is the main phototaxis photoreceptor under vegetative conditions, as it is more specifically adapted to environmental conditions and the developmental stages of Volvox.}, } @article {pmid19639166, year = {2009}, author = {Sinkovics, JG}, title = {Horizontal gene transfers and cell fusions in microbiology, immunology and oncology (Review).}, journal = {International journal of oncology}, volume = {35}, number = {3}, pages = {441-465}, doi = {10.3892/ijo_00000357}, pmid = {19639166}, issn = {1019-6439}, mesh = {Allergy and Immunology ; Animals ; *Cell Fusion ; Cell Transformation, Neoplastic/*genetics ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; Humans ; Microbiology ; }, abstract = {Evolving young genomes of archaea, prokaryota and unicellular eukaryota were wide open for the acceptance of alien genomic sequences, which they often preserved and vertically transferred to their descendants throughout three billion years of evolution. Established complex large genomes, although seeded with ancestral retroelements, have come to regulate strictly their integrity. However, intruding retroelements, especially the descendents of Ty3/Gypsy, the chromoviruses, continue to find their ways into even the most established genomes. The simian and hominoid-Homo genomes preserved and accommodated a large number of endogenous retroviral genomic segments. These retroelements may mature into exogenous retroviruses, or into functional new genes. Phages and viruses have been instrumental in incorporating and transferring host cell genes. These events profoundly influenced and altered the course of evolution. Horizontal (lateral) gene transfers (HGT) overwhelmed the genomes of the ancient protocells and the evolving unicellular microorganisms, actually leading to their Cambrian explosion. While the rigidly organized genomes of multicellular organisms increasingly resist H/LGT, de-differentiated cells assuming the metabolism of their onto- or phylogenetic ancestors, open up widely to the practice of H/LGT by direct transfer, or to transfers mediated by viruses, or by cell fusions. This activity is intensified in malignantly transformed cells, thus rendering these subjects receptive to therapy with oncolytic viruses and with viral vectors of tumor-suppressive or immunogenic genetic materials. Naturally formed hybrids of dendritic and tumor cells are often tolerogenic, whereas laboratory products of these unisons may be immunogenic in the hosts of origin. As human breast cancer stem cells are induced by a treacherous class of CD8+ T cells to undergo epithelial to mesenchymal (ETM) transition and to yield to malignant transformation by the omnipresent proto-ocogenes (for example, the ras oncogenes), they become defenseless toward oncolytic viruses. Cell fusions and horizontal exchanges of genes are fundamental attributes and inherent characteristics of the living matter.}, } @article {pmid19638535, year = {2009}, author = {Nehyba, J and Hrdlicková, R and Bose, HR}, title = {Dynamic evolution of immune system regulators: the history of the interferon regulatory factor family.}, journal = {Molecular biology and evolution}, volume = {26}, number = {11}, pages = {2539-2550}, pmid = {19638535}, issn = {1537-1719}, support = {R01 CA033192/CA/NCI NIH HHS/United States ; R01 CA098151/CA/NCI NIH HHS/United States ; CA098151/CA/NCI NIH HHS/United States ; CA33192/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Duplication ; Interferon Regulatory Factors/classification/*genetics ; Invertebrates/genetics ; Phylogeny ; }, abstract = {This manuscript presents the first extensive phylogenetics analysis of a key family of immune regulators, the interferon regulatory factor (IRF) family. The IRF family encodes transcription factors that play important roles in immune defense, stress responses, reproduction, development, and carcinogenesis. Several times during their evolution, the IRF genes have undergone expansion and diversification. These genes were also completely lost on two separate occasions in large groups of metazoans. The origin of the IRF family coincides with the appearance of multicellularity in animals. IRF genes are present in all principal metazoan groups, including sea sponges, placozoans, comb jellies, cnidarians, and bilaterians. Although the number of IRF family members does not exceed two in sponges and placozoans, this number reached five in cnidarians. At least four additional independent expansions lead up to 11 members in different groups of bilaterians. In contrast, the IRF genes either disappeared or mutated beyond recognition in roundworms and insects, the two groups that include most of the metazoan species. The IRF family separated very early into two branches ultimately leading to vertebrate IRF1 and IRF4 supergroups (SGs). Genes encoding the IRF-SGs are present in all bilaterians and cnidarians. The evolution of vertebrate IRF family members further proceeded with at least two additional steps. First, close to the appearance of the first vertebrate, the IRF family probably expanded to four family members, predecessors of the four vertebrate IRF groups (IRF1, 3, 4, 5 groups). In the second step, 10 vertebrate family members evolved from these four genes, likely as a result of the 2-fold duplication of the entire genome. Interestingly, the IRF family coevolved with the Rel/NF-kappaB family with which it shares some important evolutionary characteristics, including roles in defense responses, metazoan specificity, extensive diversification in vertebrates, and elimination of all family members in nematodes.}, } @article {pmid19632181, year = {2009}, author = {Grove, CA and De Masi, F and Barrasa, MI and Newburger, DE and Alkema, MJ and Bulyk, ML and Walhout, AJ}, title = {A multiparameter network reveals extensive divergence between C. elegans bHLH transcription factors.}, journal = {Cell}, volume = {138}, number = {2}, pages = {314-327}, pmid = {19632181}, issn = {1097-4172}, support = {R01 DK068429-05/DK/NIDDK NIH HHS/United States ; R01 DK068429/DK/NIDDK NIH HHS/United States ; R01 DK068429-04/DK/NIDDK NIH HHS/United States ; R01 HG003985/HG/NHGRI NIH HHS/United States ; R01 DK068429-03/DK/NIDDK NIH HHS/United States ; R01 DK068429-01A1/DK/NIDDK NIH HHS/United States ; R01 DK068429-02/DK/NIDDK NIH HHS/United States ; R01 HG002966/HG/NHGRI NIH HHS/United States ; R01 GM084491/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Caenorhabditis elegans/genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; DNA/metabolism ; Gene Regulatory Networks ; Male ; Molecular Sequence Data ; Promoter Regions, Genetic ; Protein Multimerization ; }, abstract = {Differences in expression, protein interactions, and DNA binding of paralogous transcription factors ("TF parameters") are thought to be important determinants of regulatory and biological specificity. However, both the extent of TF divergence and the relative contribution of individual TF parameters remain undetermined. We comprehensively identify dimerization partners, spatiotemporal expression patterns, and DNA-binding specificities for the C. elegans bHLH family of TFs, and model these data into an integrated network. This network displays both specificity and promiscuity, as some bHLH proteins, DNA sequences, and tissues are highly connected, whereas others are not. By comparing all bHLH TFs, we find extensive divergence and that all three parameters contribute equally to bHLH divergence. Our approach provides a framework for examining divergence for other protein families in C. elegans and in other complex multicellular organisms, including humans. Cross-species comparisons of integrated networks may provide further insights into molecular features underlying protein family evolution. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.}, } @article {pmid19628600, year = {2009}, author = {Mori, K and Yamaguchi, K and Sakiyama, Y and Urabe, T and Suzuki, K}, title = {Caldisericum exile gen. nov., sp. nov., an anaerobic, thermophilic, filamentous bacterium of a novel bacterial phylum, Caldiserica phyl. nov., originally called the candidate phylum OP5, and description of Caldisericaceae fam. nov., Caldisericales ord. nov. and Caldisericia classis nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {59}, number = {Pt 11}, pages = {2894-2898}, doi = {10.1099/ijs.0.010033-0}, pmid = {19628600}, issn = {1466-5026}, mesh = {Anaerobiosis ; Bacteria/*classification/genetics/*isolation & purification/metabolism ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fatty Acids/metabolism ; Hot Springs/*microbiology ; Hot Temperature ; Molecular Sequence Data ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {An anaerobic, thermophilic, thiosulfate-reducing bacterium, strain AZM16c01(T), isolated from a hot spring in Japan [Mori, K., Sunamura, M., Yanagawa, K., Ishibashi, J., Miyoshi, Y., Iino, T., Suzuki, K. & Urabe, T. (2008). Appl Environ Microbiol 74, 6223-6229] was characterized in detail. The 16S rRNA gene sequence analysis had revealed that strain AZM16c01(T) was the first cultivated representative of the candidate phylum OP5. The cells were multicellular filaments with a single polar flagellum. The strain contained iso-C(17 : 0) as the major fatty acid and menaquinone-8(H(6)), menaquinone-8(H(8)) and menaquinone-8(H(10)) as the respiratory quinones. The G+C content of the genomic DNA of strain AZM16c01(T) was 34.6 mol%. Optimum growth was obtained at 65 degrees C, pH 6.5 and in the absence of NaCl, with a doubling time of 10.6 h. On the basis of the results of phylogenetic analysis based on the 16S rRNA gene sequence and the characterization of the strain in this study, we propose the name Caldisericum exile gen. nov., sp. nov. for strain AZM16c01(T) (=NBRC 104410(T)=DSM 21853(T)). In addition, we propose the new phylum name Caldiserica phyl. nov. for the candidate phylum OP5 represented by C. exile gen. nov., sp. nov., and Caldisericaceae fam. nov., Caldisericales ord. nov. and Caldisericia classis nov.}, } @article {pmid19623209, year = {2009}, author = {Hörandl, E}, title = {A combinational theory for maintenance of sex.}, journal = {Heredity}, volume = {103}, number = {6}, pages = {445-457}, pmid = {19623209}, issn = {1365-2540}, support = {P 19006/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; Biological Evolution ; Eukaryota/*genetics/physiology ; Female ; Humans ; Male ; *Recombination, Genetic ; *Reproduction ; Sex Characteristics ; }, abstract = {Sexual reproduction implies high costs, but it is difficult to give evidence for evolutionary advantages that would explain the predominance of meiotic sex in eukaryotes. A combinational theory discussing evolution, maintenance and loss of sex may resolve the problem. The main function of sex is the restoration of DNA and consequently a higher quality of offspring. Recombination at meiosis evolved, perhaps, as a repair mechanism of DNA strand damages. This mechanism is most efficient for DNA restoration in multicellular eukaryotes, because the initial cell starts with a re-optimized genome, which is passed to all the daughter cells. Meiosis acts also as creator of variation in haploid stages, in which selection can purge most efficiently deleterious mutations. A prolonged diploid phase buffers the effects of deleterious recessive alleles as well as epigenetic defects and is thus optimal for prolonged growth periods. For complex multicellular organisms, the main advantage of sexuality is thus the alternation of diploid and haploid stages, combining advantages of both. A loss of sex is constrained by several, partly group-specific, developmental features. Hybridization may trigger shifts from sexual to asexual reproduction, but crossing barriers of the parental sexual species limit this process. For the concerted break-up of meiosis-outcrossing cycles plus silencing of secondary features, various group-specific changes in the regulatory system may be required. An establishment of asexuals requires special functional modifications and environmental opportunities. Costs for maintenance of meiotic sex are consequently lower than a shift to asexual reproduction.}, } @article {pmid19616606, year = {2009}, author = {Zong, J and Yao, X and Yin, J and Zhang, D and Ma, H}, title = {Evolution of the RNA-dependent RNA polymerase (RdRP) genes: duplications and possible losses before and after the divergence of major eukaryotic groups.}, journal = {Gene}, volume = {447}, number = {1}, pages = {29-39}, doi = {10.1016/j.gene.2009.07.004}, pmid = {19616606}, issn = {1879-0038}, mesh = {Animals ; Eukaryotic Cells/metabolism ; *Evolution, Molecular ; *Gene Duplication ; Genetic Variation/*genetics ; Humans ; Models, Theoretical ; Phylogeny ; RNA-Dependent RNA Polymerase/*genetics/metabolism ; }, abstract = {Eukaryotic RNA-dependent RNA polymerases (RdRPs, encoded by RDR genes) play critical roles in developmental regulation, maintenance of genome integrity, and defense against foreign nucleic acids. However, the phylogenetic relationship of RDRs remains unclear. From available genome sequences, we identified 161 putative RDR genes from 56 eukaryotes, ranging from protists to multicellular organisms, including plants, fungi and invertebrate animals, such as nematodes, lancelet and sea anemone. On the other hand, we did not detect RDR homologs in vertebrates and insects, even though RNA interference functions in these organisms. Our phylogenetic analysis of the RDR genes suggests that the eukaryotic ancestor might have had three copies, i.e. RDRalpha, RDRbeta and RDRgamma. These three ancient copies were also supported by the patterns of protein sequence motifs. Further duplication events after the divergence of major eukaryotic groups were supported by the phylogenetic analyses, including some that likely occurred before the separation of subgroups within each kingdom. We present a model for a possible evolutionary history of RDR genes in eukaryotes.}, } @article {pmid19614595, year = {2009}, author = {Kienle, N and Kloepper, TH and Fasshauer, D}, title = {Differences in the SNARE evolution of fungi and metazoa.}, journal = {Biochemical Society transactions}, volume = {37}, number = {Pt 4}, pages = {787-791}, doi = {10.1042/BST0370787}, pmid = {19614595}, issn = {1470-8752}, mesh = {Animals ; *Evolution, Molecular ; Fungal Proteins/*genetics ; Fungi/genetics/*physiology ; SNARE Proteins/*genetics ; }, abstract = {Proteins of the SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) family are key factors in all vesicle-fusion steps in the endocytic and secretory pathways. SNAREs can assemble into a tight four-helix bundle complex between opposing membranes, a process that is thought to pull the two membranes into close proximity. The complex-forming domains are highly conserved, not only between different species, but also between different vesicular trafficking steps. SNARE protein sequences can be classified into four main types (Qa, Qb, Qc and R), each reflecting their position in the four-helix bundle. Further refinement of these main types resulted in the identification of 20 distinct conserved groups, which probably reflect the original repertoire of a proto-eukaryotic cell. We analysed the evolution of the SNARE repertoires in metazoa and fungi and unveiled remarkable differences in both lineages. In metazoa, the SNARE repertoire appears to have undergone a substantial expansion, particularly in the endosomal pathways. This expansion probably occurred during the transition from a unicellular to a multicellular lifestyle. We also observed another expansion that led to a major increase of the secretory SNAREs in the vertebrate lineage. Interestingly, fungi developed multicellularity independently, but in contrast with plants and metazoa, this change was not accompanied by an expansion of the SNARE set. Our findings suggest that the rise of multicellularity is not generally linked to an expansion of the SNARE set. The structural and functional diversity that exists between fungi and metazoa might offer a simple explanation for the distinct evolutionary history of their SNARE repertoires.}, } @article {pmid19601972, year = {2009}, author = {Hughes, AL and Friedman, R}, title = {A phylogenetic approach to gene expression data: evidence for the evolutionary origin of mammalian leukocyte phenotypes.}, journal = {Evolution & development}, volume = {11}, number = {4}, pages = {382-390}, pmid = {19601972}, issn = {1525-142X}, support = {R01 GM043940/GM/NIGMS NIH HHS/United States ; R01 GM043940-20/GM/NIGMS NIH HHS/United States ; GM43940/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Cell Lineage ; Gene Expression ; Humans ; Mammals/*genetics/*immunology/metabolism ; Phylogeny ; Th1 Cells/*metabolism ; Th2 Cells/*metabolism ; }, abstract = {The evolution of multicellular organisms involved the evolution of specialized cell types performing distinct functions; and specialized cell types presumably arose from more generalized ancestral cell types as a result of mutational event, such as gene duplication and changes in gene expression. We used characters based on gene expression data to reconstruct evolutionary relationships among 11 types of lymphocytes by the maximum parsimony method. The resulting phylogenetic tree showed expected patterns including separation of the lymphoid and myeloid lineages; clustering together of granulocyte types; and pairing of phenotypically similar cell types such as T-helper cells type 1 and T-helper cells type 2 (Th1 and Th2). We used phylogenetic analyses of sequence data to determine the time of origin of genes showing significant expression difference between Th1 and Th2 cells. Many such genes, particularly those involved in the regulation of gene expression or activation of proteins, were of ancient origin, having arisen by gene duplication before the most recent common ancestor (MRCA) of tetrapods and teleosts. However, certain other genes with significant expression difference between Th1 and Th2 arose after the tetrapod-teleost MRCA, and some of the latter were specific to eutherian (placental) mammals. This evolutionary pattern is consistent with previous evidence that, while bony fishes possess Th1 and Th2 cells, the latter differ phenotypically in important respects from the corresponding cells of mammals. Our results support a gradualistic model of the evolution of distinctive cellular phenotypes whereby the unique characteristics of a given cell type arise as a result of numerous independent mutational changes over hundreds of millions of years.}, } @article {pmid19598130, year = {2009}, author = {Pfannkuchen, M and Brümmer, F}, title = {Heterologous expression of DsRed2 in young sponges (Porifera).}, journal = {The International journal of developmental biology}, volume = {53}, number = {7}, pages = {1113-1117}, doi = {10.1387/ijdb.072526mp}, pmid = {19598130}, issn = {1696-3547}, mesh = {Animals ; Animals, Genetically Modified ; Cytomegalovirus/genetics ; Luminescent Proteins/*genetics ; Microscopy, Fluorescence ; Porifera/*genetics/*growth & development ; Promoter Regions, Genetic ; Recombinant Proteins/genetics ; Transfection ; }, abstract = {Sponges (Porifera) are currently considered to be the first branch off the Urmetazoa, common ancestors of all multicellular animals or metazoa. Research in the field of the developmental biology of sponges was restricted to morphological observations. Nowadays, research is mainly concentrated on larval development, primarily dealing with tissue formation. Already since 1907, methods for developing functional sponges from stem cells have been at hand. Functional freshwater sponges can be grown from stem cell populations originating from gemmulae. A number of poriferan sequences with high similarity to regulative genes in higher metazoa have already been found. We have now succeeded in heterologously expressing the red fluorescent protein DsRedN1 under the control of the cytomegalovirus promoter in young specimens of the freshwater sponge Spongilla lacustris. The protein folded correctly, polymerized and subsequently was detected by fluorescence microscopy. Reporting this expression system, we now consider this appealing system for early meatazoan development to be ready for molecular developmental biology and functional genetics research.}, } @article {pmid19591675, year = {2009}, author = {Lerche, K and Hallmann, A}, title = {Stable nuclear transformation of Gonium pectorale.}, journal = {BMC biotechnology}, volume = {9}, number = {}, pages = {64}, pmid = {19591675}, issn = {1472-6750}, mesh = {3' Flanking Region ; 5' Flanking Region ; Base Sequence ; Chlorophyta/*genetics ; DNA, Algal/genetics ; Genes, Reporter ; Genetic Engineering/*methods ; Kanamycin Kinase/*genetics ; Molecular Sequence Data ; Phylogeny ; Promoter Regions, Genetic ; Streptomyces/enzymology ; *Transformation, Genetic ; }, abstract = {BACKGROUND: Green algae of the family Volvocaceae are a model lineage for studying the molecular evolution of multicellularity and cellular differentiation. The volvocine alga Gonium is intermediate in organizational complexity between its unicellular relative, Chlamydomonas, and its multicellular relatives with differentiated cell types, such as Volvox. Gonium pectorale consists of approximately 16 biflagellate cells arranged in a flat plate. The detailed molecular analysis of any species necessitates its accessibility to genetic manipulation, but, in volvocine algae, transformation procedures have so far only been established for Chlamydomonas reinhardtii and Volvox carteri.

RESULTS: Stable nuclear transformation of G. pectorale was achieved using a heterologous dominant antibiotic resistance gene, the aminoglycoside 3'-phosphotransferase VIII gene (aphVIII) of Streptomyces rimosus, as a selectable marker. Heterologous 3'- and 5'-untranslated flanking sequences, including promoters, were from Chlamydomonas reinhardtii or from Volvox carteri. After particle gun bombardment of wild type Gonium cells with plasmid-coated gold particles, transformants were recovered. The transformants were able to grow in the presence of the antibiotic paromomycin and produced a detectable level of the AphVIII protein. The plasmids integrated into the genome, and stable integration was verified after propagation for over 1400 colony generations. Co-transformants were recovered with a frequency of approximately 30-50% when cells were co-bombarded with aphVIII-based selectable marker plasmids along with unselectable plasmids containing heterologous genes. The transcription of the co-transformed, unselectable genes was confirmed. After heterologous expression of the luciferase gene from the marine copepod Gaussia princeps, which was previously engineered to match the codon usage in C. reinhardtii, Gonium transformants show luciferase activity through light emission in bioluminescence assays.

CONCLUSION: Flanking sequences that include promoters from C. reinhardtii and from V. carteri work in G. pectorale and allow the functional expression of heterologous genes, such as the selectable marker gene aphVIII of S. rimosus or the co-transformed, codon-optimized G. princeps luciferase gene, which turned out to be a suitable reporter gene in Gonium. The availability of a method for transformation of Gonium makes genetic engineering of this species possible and allows for detailed studies in molecular evolution using the unicellular Chlamydomonas, the 16-celled Gonium, and the multicellular Volvox.}, } @article {pmid19590530, year = {2009}, author = {Russell, DG and Vanderven, BC and Glennie, S and Mwandumba, H and Heyderman, RS}, title = {The macrophage marches on its phagosome: dynamic assays of phagosome function.}, journal = {Nature reviews. Immunology}, volume = {9}, number = {8}, pages = {594-600}, pmid = {19590530}, issn = {1474-1741}, support = {S10 RR023455-01/RR/NCRR NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R01 AI067027-04/AI/NIAID NIH HHS/United States ; S10 RR023455/RR/NCRR NIH HHS/United States ; R01 AI067027/AI/NIAID NIH HHS/United States ; R01 AI057086/AI/NIAID NIH HHS/United States ; R01 AI057086-06A2/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigen Presentation/immunology ; Biological Assay ; Cytokines/immunology/metabolism ; Humans ; Hydrolases/immunology/metabolism ; Hydrolysis ; Lysosomes/immunology/*metabolism ; Macrophage Activation/*immunology ; Macrophages/*immunology/metabolism ; Phagosomes/immunology/*metabolism ; Toll-Like Receptors/immunology/metabolism ; }, abstract = {Professional phagocytes ingest particulate material to fulfil a diverse array of functions in a multicellular organism. The ancestral function of phagosomes is digestion; however, through evolution this degradative capacity has become pivotal to the adaptive immune response by processing antigens to be presented to lymphocytes. Moreover, phagocytes have also acquired an active role in microbial killing. This Innovation article describes new assays that probe the biological activities which occur within phagosomes. These assays provide functional insights into how the phagosome fulfils its diverse roles in homeostasis and in innate and adaptive immune responses.}, } @article {pmid19589966, year = {2009}, author = {Tan, CS and Pasculescu, A and Lim, WA and Pawson, T and Bader, GD and Linding, R}, title = {Positive selection of tyrosine loss in metazoan evolution.}, journal = {Science (New York, N.Y.)}, volume = {325}, number = {5948}, pages = {1686-1688}, pmid = {19589966}, issn = {1095-9203}, support = {R01 GM055040/GM/NIGMS NIH HHS/United States ; R01 GM055040-11/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; Animals ; *Biological Evolution ; *Evolution, Molecular ; Fungal Proteins/chemistry/metabolism ; Glycosylation ; Humans ; Methylation ; Mutation ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases/*metabolism ; Proteins/*chemistry/*metabolism ; *Selection, Genetic ; *Signal Transduction ; Substrate Specificity ; Tyrosine/*metabolism ; }, abstract = {John Nash showed that within a complex system, individuals are best off if they make the best decision that they can, taking into account the decisions of the other individuals. Here, we investigate whether similar principles influence the evolution of signaling networks in multicellular animals. Specifically, by analyzing a set of metazoan species we observed a striking negative correlation of genomically encoded tyrosine content with biological complexity (as measured by the number of cell types in each organism). We discuss how this observed tyrosine loss correlates with the expansion of tyrosine kinases in the evolution of the metazoan lineage and how it may relate to the optimization of signaling systems in multicellular animals. We propose that this phenomenon illustrates genome-wide adaptive evolution to accommodate beneficial genetic perturbation.}, } @article {pmid19589395, year = {2010}, author = {Phochanukul, N and Russell, S}, title = {No backbone but lots of Sox: Invertebrate Sox genes.}, journal = {The international journal of biochemistry & cell biology}, volume = {42}, number = {3}, pages = {453-464}, doi = {10.1016/j.biocel.2009.06.013}, pmid = {19589395}, issn = {1878-5875}, support = {BB/E015492/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Drosophila/genetics ; Invertebrates/*genetics ; Multigene Family/genetics ; SOX Transcription Factors/*genetics ; }, abstract = {Sox transcription factors are intimately involved in the development of multicellular organisms and accordingly understanding the role Sox genes play in diverse species of metazoans will hopefully shed light on the evolution of multicellularity. Here we review our current knowledge of the Sox genes isolated and characterised in invertebrates, ranging from the very simplest organisms through to complex chordates. While Sox genes have been identified in many invertebrate species, comparatively little is known about their functions outside the well-studied models, Drosophila, sea urchin and nematode. Consequently, we centre this review around the Sox family in Drosophila, comparing this with what is known about orthologous genes in other invertebrate species. We highlight several conserved themes that emerge when looking at the roles Sox proteins appear to play during embryogenesis, including early functions in CNS development and widespread interactions with the Wnt signalling pathway. Comparing the expression of Sox genes in insect species, where genome organisation is conserved but expression is apparently not, highlights the need for more functional data on the roles that related Sox proteins play in organisms outside the well-characterised models.}, } @article {pmid19589182, year = {2009}, author = {Kurisu, S and Takenawa, T}, title = {The WASP and WAVE family proteins.}, journal = {Genome biology}, volume = {10}, number = {6}, pages = {226}, pmid = {19589182}, issn = {1474-760X}, mesh = {Evolution, Molecular ; Humans ; Protein Structure, Tertiary ; Protein Transport ; Wiskott-Aldrich Syndrome Protein/chemistry/genetics/*metabolism ; }, abstract = {All eukaryotic cells need to reorganize their actin cytoskeleton to change shape, divide, move, and take up nutrients for survival. The Wiskott-Aldrich syndrome protein (WASP) and WASP-family verprolin-homologous protein (WAVE) family proteins are fundamental actin-cytoskeleton reorganizers found throughout the eukaryotes. The conserved function across species is to receive upstream signals from Rho-family small GTPases and send them to activate the Arp2/3 complex, leading to rapid actin polymerization, which is critical for cellular processes such as endocytosis and cell motility. Molecular and cell biological studies have identified a wide array of regulatory molecules that bind to the WASP and WAVE proteins and give them diversified roles in distinct cellular locations. Genetic studies using model organisms have also improved our understanding of how the WASP- and WAVE-family proteins act to shape complex tissue architectures. Current efforts are focusing on integrating these pieces of molecular information to draw a unified picture of how the actin cytoskeleton in a single cell works dynamically to build multicellular organization.}, } @article {pmid19578098, year = {2009}, author = {Nedelcu, AM}, title = {Environmentally induced responses co-opted for reproductive altruism.}, journal = {Biology letters}, volume = {5}, number = {6}, pages = {805-808}, pmid = {19578098}, issn = {1744-957X}, mesh = {Acclimatization/*genetics ; Altruism ; *Biological Evolution ; Chlamydomonas reinhardtii/*genetics ; Darkness ; Gene Expression ; Phosphorus ; *Reproduction, Asexual ; *Stress, Physiological ; Sulfur ; }, abstract = {Reproductive altruism is an extreme form of altruism best typified by sterile castes in social insects and somatic cells in multicellular organisms. Although reproductive altruism is central to the evolution of multicellularity and eusociality, the mechanistic basis for the evolution of this behaviour is yet to be deciphered. Here, we report that the gene responsible for the permanent suppression of reproduction in the somatic cells of the multicellular green alga, Volvox carteri, evolved from a gene that in its unicellular relative, Chlamydomonas reinhardtii, is part of the general acclimation response to various environmental stress factors, which includes the temporary suppression of reproduction. Furthermore, we propose a model for the evolution of soma, in which by simulating the acclimation signal (i.e. a change in cellular redox status) in a developmental rather than environmental context, responses beneficial to a unicellular individual can be co-opted into an altruistic behaviour at the group level. The co-option of environmentally induced responses for reproductive altruism can contribute to the stability of this behaviour, as the loss of such responses would be costly for the individual. This hypothesis also predicts that temporally varying environments, which will select for more efficient acclimation responses, are likely to be more conducive to the evolution of reproductive altruism.}, } @article {pmid19576222, year = {2009}, author = {Sawarkar, R and Visweswariah, SS and Nellen, W and Nanjundiah, V}, title = {Histone deacetylases regulate multicellular development in the social amoeba Dictyostelium discoideum.}, journal = {Journal of molecular biology}, volume = {391}, number = {5}, pages = {833-848}, doi = {10.1016/j.jmb.2009.06.067}, pmid = {19576222}, issn = {1089-8638}, mesh = {Acetylation ; Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Cyclic AMP/metabolism ; *Dictyostelium/enzymology/genetics/growth & development ; Enzyme Inhibitors/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation ; Gene Knockout Techniques ; Histone Deacetylase Inhibitors ; Histone Deacetylases/classification/genetics/*metabolism ; Histones/metabolism ; Humans ; Hydroxamic Acids/metabolism ; Molecular Sequence Data ; Phylogeny ; Protozoan Proteins/antagonists & inhibitors/classification/genetics/*metabolism ; Sequence Alignment ; Signal Transduction/physiology ; }, abstract = {Epigenetic modifications of histones regulate gene expression and lead to the establishment and maintenance of cellular phenotypes during development. Histone acetylation depends on a balance between the activities of histone acetyltransferases and histone deacetylases (HDACs) and influences transcriptional regulation. In this study, we analyse the roles of HDACs during growth and development of one of the cellular slime moulds, the social amoeba Dictyostelium discoideum. The inhibition of HDAC activity by trichostatin A results in histone hyperacetylation and a delay in cell aggregation and differentiation. Cyclic AMP oscillations are normal in starved amoebae treated with trichostatin A but the expression of a subset of cAMP-regulated genes is delayed. Bioinformatic analysis indicates that there are four genes encoding putative HDACs in D. discoideum. Using biochemical, genetic and developmental approaches, we demonstrate that one of these four genes, hdaB, is dispensable for growth and development under laboratory conditions. A knockout of the hdaB gene results in a social context-dependent phenotype: hdaB(-) cells develop normally but sporulate less efficiently than the wild type in chimeras. We infer that HDAC activity is important for regulating the timing of gene expression during the development of D. discoideum and for defining aspects of the phenotype that mediate social behaviour in genetically heterogeneous groups.}, } @article {pmid19575567, year = {2009}, author = {Velicer, GJ and Vos, M}, title = {Sociobiology of the myxobacteria.}, journal = {Annual review of microbiology}, volume = {63}, number = {}, pages = {599-623}, doi = {10.1146/annurev.micro.091208.073158}, pmid = {19575567}, issn = {1545-3251}, support = {R01 GM079690-02/GM/NIGMS NIH HHS/United States ; GM07690/GM/NIGMS NIH HHS/United States ; R01 GM079690-01/GM/NIGMS NIH HHS/United States ; R01 GM079690-03/GM/NIGMS NIH HHS/United States ; R01 GM079690/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Gene Expression Regulation, Bacterial ; Locomotion ; Myxococcus xanthus/genetics/*physiology ; Signal Transduction ; Spores, Bacterial/physiology ; }, abstract = {Cooperation is integral to much of biological life but can be threatened by selfish evolutionary strategies. Diverse cooperative traits have evolved among microbes, but particularly sophisticated forms of sociality have arisen in the myxobacteria, including group motility and multicellular fruiting body development. Myxobacterial cooperation has succeeded against socially destructive cheaters and can readily re-evolve from some socially defective genotypes. However, social harmony does not extend far. Spatially structured natural populations of the model species Myxococcus xanthus have fragmented into a large number of socially incompatible genotypes that exclude, exploit, and/or antagonize one another, including genetically similar neighbors. Here, we briefly review basic social evolution concepts as they pertain to microbes, discuss potential benefits of myxobacterial social traits, highlight recent empirical studies of social evolution in M. xanthus, and consider their implications for how myxobacterial cooperation and conflict evolve in the wild.}, } @article {pmid19571239, year = {2009}, author = {Dagan, T and Martin, W}, title = {Getting a better picture of microbial evolution en route to a network of genomes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {364}, number = {1527}, pages = {2187-2196}, pmid = {19571239}, issn = {1471-2970}, mesh = {Archaea/*genetics ; Bacteria/*genetics ; Classification/*methods ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Genome/*genetics ; *Phylogeny ; }, abstract = {Most current thinking about evolution is couched in the concept of trees. The notion of a tree with recursively bifurcating branches representing recurrent divergence events is a plausible metaphor to describe the evolution of multicellular organisms like vertebrates or land plants. But if we try to force the tree metaphor onto the whole of the evolutionary process, things go badly awry, because the more closely we inspect microbial genomes through the looking glass of gene and genome sequence comparisons, the smaller the amount of the data that fits the concept of a bifurcating tree becomes. That is mainly because among microbes, endosymbiosis and lateral gene transfer are important, two mechanisms of natural variation that differ from the kind of natural variation that Darwin had in mind. For such reasons, when it comes to discussing the relationships among all living things, that is, including the microbes and all of their genes rather than just one or a select few, many biologists are now beginning to talk about networks rather than trees in the context of evolutionary relationships among microbial chromosomes. But talk is not enough. If we were to actually construct networks instead of trees to describe the evolutionary process, what would they look like? Here we consider endosymbiosis and an example of a network of genomes involving 181 sequenced prokaryotes and how that squares off with some ideas about early cell evolution.}, } @article {pmid19566624, year = {2009}, author = {Leunissen, JL and Yi, H}, title = {Self-pressurized rapid freezing (SPRF): a novel cryofixation method for specimen preparation in electron microscopy.}, journal = {Journal of microscopy}, volume = {235}, number = {1}, pages = {25-35}, doi = {10.1111/j.1365-2818.2009.03178.x}, pmid = {19566624}, issn = {1365-2818}, mesh = {Animals ; Bacillaceae/ultrastructure ; Caenorhabditis elegans/ultrastructure ; Cryopreservation/*methods ; *Hydrostatic Pressure ; Microscopy, Electron/*methods ; Saccharomyces cerevisiae/ultrastructure ; }, abstract = {A method is described for the cryofixation of biological specimens for ultrastructural analysis and immunocytochemical detection studies. The method employs plunge freezing of specimens in a sealed capillary tube into a cryogen such as liquid propane or liquid nitrogen. Using this method a number of single-cell test specimens were well preserved. Also multicellular organisms, such as Caenorhabditis elegans, could be frozen adequately in low ionic strength media or even in water. The preservation of these unprotected specimens is comparable to that achieved with high-pressure freezing in the presence of cryoprotectant. The results are explained by the fact that cooling of water in a confined space below the melting point gives rise to pressure build-up, which may originate from the conversion of a fraction of the water content into low-density hexagonal ice and/or expansion of water during supercooling. Calculations indicate the pressure may be similar in magnitude to that applied in high-pressure freezing. Because the specimens are plunge cooled, suitable cryogens are not limited to liquid nitrogen. It is shown that a range of cryogens and cryogen temperatures can be used successfully. Because the pressure is generated inside the specimen holders as a result of the cooling rather than applied from an external source as in high-pressure freezing, the technique has been referred to as self-pressurized rapid freezing.}, } @article {pmid19560282, year = {2009}, author = {Lauc, G and Zoldos, V}, title = {Epigenetic regulation of glycosylation could be a mechanism used by complex organisms to compete with microbes on an evolutionary scale.}, journal = {Medical hypotheses}, volume = {73}, number = {4}, pages = {510-512}, doi = {10.1016/j.mehy.2009.03.059}, pmid = {19560282}, issn = {1532-2777}, mesh = {Animals ; Bacteria/*genetics ; *Biological Evolution ; Competitive Behavior/*physiology ; Epigenesis, Genetic/*genetics ; *Evolution, Molecular ; *Glycosylation ; Humans ; *Models, Genetic ; }, abstract = {Glycosylation is the most diverse post-translational protein modification. It is essential for multicellular life and its complete absence is embryonically lethal. Hundreds of specific enzymes are involved in the synthesis of complex oligosaccharide structures that are covalently bound to protein backbones. This process is not template driven and thus results in a huge complexity of glycoproteome, estimated to be several orders of magnitude larger than proteome. Large structural variability provided by glycans represents a significant evolutionary advantage and nearly all proteins invented after the appearance of the multicellular life are glycosylated. Glycosylation represents a way how complex organisms could develop novel structural features without introducing probably deleterious changes in their genome. Intricate mechanisms by which the interplay of gene expression and intracellular localization of their products give rise to specific glycan structures is only starting to be understood, but some evidence suggests that epigenetic regulation of glycosylation might be used to create novel biological structures. Here we suggest a hypothesis that epigenetic regulation of genes involved in glycan synthesis might represent a way how newly developed structural advantages could be transmitted through generations, thus providing a tool for complex organisms to compete with high speed of evolution of unicellular organisms.}, } @article {pmid19557675, year = {2009}, author = {Newman, SA}, title = {Limb pattern, physical mechanisms and morphological evolution - an interview with Stuart A. Newman. Interviewed by Chuong, Cheng-Ming.}, journal = {The International journal of developmental biology}, volume = {53}, number = {5-6}, pages = {663-671}, doi = {10.1387/ijdb.072553cc}, pmid = {19557675}, issn = {1696-3547}, mesh = {Animals ; Biological Evolution ; Body Patterning ; Developmental Biology/methods ; Diffusion ; Humans ; Limb Buds/*embryology/*physiology ; Models, Biological ; Systems Biology ; }, abstract = {Stuart A. Newman grew up in New York City. He received a Bachelor of Arts from Columbia University and obtained a Ph.D. in chemical physics from the University of Chicago in 1970. He did post-doctoral studies in several institutions and disciplines with a focus on theoretical and developmental biology. He had a rich experience interacting with people like Stuart Kauffman, Arthur Winfree, Brian Goodwin, and John W. Saunders, Jr. He was also exposed to many interesting experimental models of development. These early experiences fostered his interest in biological pattern formation. He joined the State University of New York at Albany as a junior faculty member when Saunders was still there. With his physical science background, Newmans approach to limb bud patterning was refreshing. In his major Science paper in 1979, he and H.L. Frisch proposed a model showing how reaction-diffusion can produce chemical standing waves to set up limb skeletal patterns. He then used limb bud micromass cultures for further development and testing of the model. Extending earlier ideas, he developed a comprehensive framework for the role of physical mechanisms (diffusion, differential adhesion, oscillation, dynamical multistability, reaction diffusion, mechano-chemical coupling, etc.) in morphogenesis. He also applied these mechanisms to understand the origin of multicellularity and evolution of novel body plans. Here Newman reflects on his intellectual growth, and shares with us his ideas on how pattern formation works, and how generic physical mechanisms interact with genetic mechanisms to achieve the evolution and development of animal forms.}, } @article {pmid19531358, year = {2009}, author = {Massarwa, R and Schejter, ED and Shilo, BZ}, title = {Apical secretion in epithelial tubes of the Drosophila embryo is directed by the Formin-family protein Diaphanous.}, journal = {Developmental cell}, volume = {16}, number = {6}, pages = {877-888}, doi = {10.1016/j.devcel.2009.04.010}, pmid = {19531358}, issn = {1878-1551}, mesh = {Actin Cytoskeleton/metabolism ; Actins/metabolism ; Animals ; Biological Transport ; Carrier Proteins/genetics/*metabolism ; *Cell Polarity ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/*cytology/*embryology/metabolism ; Embryo, Nonmammalian/*cytology/metabolism ; Epithelium/*metabolism ; Formins ; Gene Expression Regulation, Developmental ; Guanine Nucleotide Exchange Factors/metabolism ; Microfilament Proteins/*metabolism ; Mutation/genetics ; Myosin Type V/metabolism ; RNA, Messenger/genetics/metabolism ; Rho Guanine Nucleotide Exchange Factors ; Secretory Vesicles/metabolism ; rho GTP-Binding Proteins/metabolism ; }, abstract = {Apical localization of filamentous actin (F-actin) is a common feature of epithelial tubes in multicellular organisms. However, its origins and function are not known. We demonstrate that the Diaphanous (Dia)/Formin actin-nucleating factor is required for generation of apical F-actin in diverse types of epithelial tubes in the Drosophila embryo. Dia itself is apically localized both at the RNA and protein levels, and apical localization of its activators, including Rho1 and two guanine exchange factor proteins (Rho-GEFs), contributes to its activity. In the absence of apical actin polymerization, apical-basal polarity and microtubule organization of tubular epithelial cells remain intact; however, secretion through the apical surface to the lumen of tubular organs is blocked. Apical secretion also requires the Myosin V (MyoV) motor, implying that secretory vesicles are targeted to the apical membrane by MyoV-based transport, along polarized actin filaments nucleated by Dia. This mechanism allows efficient utilization of the entire apical membrane for secretion.}, } @article {pmid19530675, year = {2009}, author = {Zielinska, DF and Gnad, F and Jedrusik-Bode, M and Wiśniewski, JR and Mann, M}, title = {Caenorhabditis elegans has a phosphoproteome atypical for metazoans that is enriched in developmental and sex determination proteins.}, journal = {Journal of proteome research}, volume = {8}, number = {8}, pages = {4039-4049}, doi = {10.1021/pr900384k}, pmid = {19530675}, issn = {1535-3893}, mesh = {Adenosine Triphosphatases ; Animals ; Caenorhabditis elegans/genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cluster Analysis ; Conserved Sequence ; DNA-Binding Proteins ; Databases, Genetic ; Multiprotein Complexes ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; Phosphoserine ; Phosphothreonine ; Phosphotransferases ; Phylogeny ; Proteome/genetics/*metabolism ; Proteomics/*methods ; Sex Determination Processes ; }, abstract = {In eukaryotic species, signal transduction is often mediated by posttranslational modifications that can serve as regulatory switches. Although nematodes have usually been studied by genetic rather than biochemical methods, PTMs such as phosphorylation are thought to control all aspects of biological functions including sex determination and development. Here, we apply high accuracy mass spectrometry and comprehensive bioinformatic analysis to determine and characterize the in vivo Caenorhabditis elegans phosphoproteome for the first time. We detect nearly 7000 phosphorylation sites on 2400 proteins, which are disproportionately involved in development and sex determination. Interestingly, the worm phosphoproteome turns out to be very distinct from phosphoproteomes of other multicellular eukaryotes as judged by its phylogenetic conservation, kinase substrate motifs and site analysis by a support vector machine. This result agrees with the large proportion of worm specific kinases previously discovered by genome sequencing. Furthermore, our data show that the C. elegans specific dosage complex can be phosphorylated on most subunits, suggesting its regulation by kinases. Availability of the C. elegans phosphoproteome should add a novel dimension to functional data obtained by genetic screens in this organism.}, } @article {pmid19530132, year = {2009}, author = {Aravind, L and Anantharaman, V and Venancio, TM}, title = {Apprehending multicellularity: regulatory networks, genomics, and evolution.}, journal = {Birth defects research. Part C, Embryo today : reviews}, volume = {87}, number = {2}, pages = {143-164}, pmid = {19530132}, issn = {1542-9768}, support = {Z01 LM594244-01/ImNIH/Intramural NIH HHS/United States ; Z99 LM999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Eukaryotic Cells/metabolism ; *Evolution, Molecular ; Gene Expression Regulation/*genetics ; *Gene Regulatory Networks ; *Genomics ; Humans ; Phylogeny ; Proteomics ; Receptors, Notch/genetics ; Sequence Alignment ; }, abstract = {The genomic revolution has provided the first glimpses of the architecture of regulatory networks. Combined with evolutionary information, the "network view" of life processes leads to remarkable insights into how biological systems have been shaped by various forces. This understanding is critical because biological systems, including regulatory networks, are not products of engineering but of historical contingencies. In this light, we attempt a synthetic overview of the natural history of regulatory networks operating in the development and differentiation of multicellular organisms. We first introduce regulatory networks and their organizational principles as can be deduced using ideas from the graph theory. We then discuss findings from comparative genomics to illustrate the effects of lineage-specific expansions, gene-loss, and nonprotein-coding DNA on the architecture of networks. We consider the interaction between expansions of transcription factors, and cis regulatory and more general chromatin state stabilizing elements in the emergence of morphological complexity. Finally, we consider a case study of the Notch subnetwork, which is present throughout Metazoa, to examine how such a regulatory system has been pieced together in evolution from new innovations and pre-existing components that were originally functionally distinct.}, } @article {pmid19528647, year = {2009}, author = {Lukes, J and Leander, BS and Keeling, PJ}, title = {Cascades of convergent evolution: the corresponding evolutionary histories of euglenozoans and dinoflagellates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {106 Suppl 1}, number = {Suppl 1}, pages = {9963-9970}, pmid = {19528647}, issn = {1091-6490}, mesh = {Adaptation, Physiological/physiology ; Animals ; Dinoflagellida/*physiology ; Euglenida/*physiology ; *Evolution, Molecular ; Gene Expression Regulation/*physiology ; Genes, Protozoan/*physiology ; *Phylogeny ; }, abstract = {The majority of eukaryotic diversity is hidden in protists, yet our current knowledge of processes and structures in the eukaryotic cell is almost exclusively derived from multicellular organisms. The increasing sensitivity of molecular methods and growing interest in microeukaryotes has only recently demonstrated that many features so far considered to be universal for eukaryotes actually exist in strikingly different versions. In other words, during their long evolutionary histories, protists have solved general biological problems in many more ways than previously appreciated. Interestingly, some groups have broken more rules than others, and the Euglenozoa and the Alveolata stand out in this respect. A review of the numerous odd features in these 2 groups allows us to draw attention to the high level of convergent evolution in protists, which perhaps reflects the limits that certain features can be altered. Moreover, the appearance of one deviation in an ancestor can constrain the set of possible downstream deviations in its descendents, so features that might be independent functionally, can still be evolutionarily linked. What functional advantage may be conferred by the excessive complexity of euglenozoan and alveolate gene expression, organellar genome structure, and RNA editing and processing has been thoroughly debated, but we suggest these are more likely the products of constructive neutral evolution, and as such do not necessarily confer any selective advantage at all.}, } @article {pmid19523039, year = {2009}, author = {Jarvis, JP and Cheverud, JM}, title = {Epistasis and the evolutionary dynamics of measured genotypic values during simulated serial bottlenecks.}, journal = {Journal of evolutionary biology}, volume = {22}, number = {8}, pages = {1658-1668}, doi = {10.1111/j.1420-9101.2009.01776.x}, pmid = {19523039}, issn = {1420-9101}, support = {DK-055736/DK/NIDDK NIH HHS/United States ; }, mesh = {Alleles ; Animals ; *Biological Evolution ; *Epistasis, Genetic ; Female ; Gene Frequency ; Genotype ; Male ; Mice ; Mice, Inbred Strains ; Quantitative Trait Loci ; }, abstract = {The evolutionary effects of epistasis have been primarily explored analytically and most empirical studies have utilized yeast, viral and bacterial populations. Empirical analyses in multi-cellular organisms are rare because of experimental constraints. Here, we report the results of a genome-wide scan for two-way epistasis in 16 traits related to body size and composition in F(2) mice from the LG/J by SM/J intercross. We analyze two-locus genotypic values at quantitative trait loci (QTL), which provides an especially detailed view of epistatic architectures, to evaluate their predicted evolutionary consequences via Monte Carlo simulations. Epistatic profiles vary, but all traits show complicated genetic architectures which are largely hidden in single locus QTL scans. On average, detected epistatic effects are comparable in size to marginal effects. Simulations demonstrate an expected preservation, and often inflation, of heritable variance across several generations of small effective population size for many identified epistatic pairs over a range of starting allele frequencies.}, } @article {pmid19519929, year = {2009}, author = {Ostrowski, EA and Shaulsky, G}, title = {Learning to get along despite struggling to get by.}, journal = {Genome biology}, volume = {10}, number = {5}, pages = {218}, pmid = {19519929}, issn = {1474-760X}, support = {T15 LM007093/LM/NLM NIH HHS/United States ; 5T15LM07093/LM/NLM NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Chimerism ; Cooperative Behavior ; *Selection, Genetic ; }, abstract = {How cooperation can evolve by natural selection is important for understanding the evolutionary transition from unicellular to multicellular life. Here we review the evolutionary theories for cooperation, with emphasis on the mechanisms that can favor cooperation and reduce conflict in multicellular organisms.}, } @article {pmid19513277, year = {2009}, author = {Agnati, LF and Barlow, PW and Baldelli, E and Baluska, F}, title = {Are maternal mitochondria the selfish entities that are masters of the cells of eukaryotic multicellular organisms?.}, journal = {Communicative & integrative biology}, volume = {2}, number = {2}, pages = {194-200}, pmid = {19513277}, issn = {1942-0889}, abstract = {The Energide concept, as well as the endosymbiotic theory of eukaryotic cell organization and evolution, proposes that present-day cells of eukaryotic organisms are mosaics of specialized and cooperating units, or organelles. Some of these units were originally free-living prokaryotes, which were engulfed during evolutionary time. Mitochondria represent one of these types of previously independent organisms, the Energide, is another type. This new perspective on the organization of the cell has been further expanded to reveal the concept of a public milieu, the cytosol, in which Energides and mitochondria live, each with their own private internal milieu. The present paper discusses how the endosymbiotic theory implicates a new hypothesis about the hierarchical and communicational organization of the integrated prokaryotic components of the eukaryotic cell and provides a new angle from which to consider the theory of evolution and its bearing upon cellular complexity. Thus, it is proposed that the "selfish gene" hypothesis of Dawkins1 is not the only possible perspective for comprehending genomic and cellular evolution. Our proposal is that maternal mitochondria are the selfish "master" entities of the eukaryotic cell with respect not only to their propagation from cell-to-cell and from generation-to-generation but also to their regulation of all other cellular functions. However, it should be recognized that the concept of "master" and "servant" cell components is a metaphor; in present-day living organisms their organellar components are considered to be interdependent and inseparable.}, } @article {pmid19490637, year = {2009}, author = {Shi, D and Shi, G and Huang, G and Zhang, J and Lartigau, E}, title = {Chemosensitivity of radioresistant cells in the multicellular spheroids of A549 lung adenocarcinoma.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {28}, number = {1}, pages = {72}, pmid = {19490637}, issn = {1756-9966}, mesh = {ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; Adenocarcinoma/*drug therapy/pathology/radiotherapy ; Antineoplastic Agents/*pharmacology ; Breast Neoplasms/drug therapy/pathology/radiotherapy ; Calcium Channel Blockers/pharmacology ; Cell Proliferation ; Cisplatin/pharmacology ; Dose Fractionation, Radiation ; Doxorubicin/pharmacology ; *Drug Resistance, Neoplasm ; Fluorouracil/pharmacology ; Humans ; Lung Neoplasms/*drug therapy/pathology/radiotherapy ; Mitomycin/pharmacology ; Radiation Tolerance/*drug effects ; Spheroids, Cellular/*drug effects/*radiation effects ; Tumor Cells, Cultured ; Verapamil/pharmacology ; Vindesine/pharmacology ; X-Rays ; }, abstract = {BACKGROUND: The relapse of cancer after radiotherapy is a clinical knotty problem. Previous studies have demonstrated that the elevation of several factors is likely in some way to lead to the development of treatment tolerance, so it is necessary to further explore the problem of re-proliferated radioresistant cells to chemotherapeutic agents. In the present study, we aimed to investigate the chemosensitivity of radioresistant cells originated from the multicellular spheroids of A549 lung adenocarcinoma.

METHODS: After irradiated with 25 Gy of 6 MV X-ray to A549 multicellular spheroids, whose 10th re-proliferated generations were employed as radioresistant cells, and the control groups were A549 parental cells and MCF7/VCR resistant cells. The chemo-sensitivity test was made by six kinds of chemotherapeutic drugs which were DDP, VDS, 5-Fu, HCP, MMC and ADM respectively, while verapamil (VPL) was used as the reversal agent. Then the treatment effect was evaluated by MTT assay, and the multidrug resistant gene expressions of mdr1 and MRP were measured by RT-PCR.

RESULTS: Both A549 parental cells and A549 derived radioresistant cells were resistant to DDP, but sensitive to VDS, 5-Fu, HCP, MMC and ADM. The inhibitory rates of VPL to these two types of cell were 98% and 25% respectively (P < 0.001). In addition, without drugs added, the absorbance value (A value) of A549 parental cells was 2-folds higher than that of their radioresistant cells (P < 0.001). As to the MCF7/VCR cells, they were resistant to DDP and VDS, but slight sensitive to MMC, ADM, 5-Fu, and HCP with 80% of inhibitory rate to VPL. The subsequent RT-PCR demonstrated that the Mdr1/beta2-MG and MRP/beta2-MG of all A549 cells were about 0 and 0.7 respectively, and those of MCF7/VCR cells were 35 and 4.36.

CONCLUSION: The chemosensitivity of A549 radioresistant cells had not changed markedly, and the decreased sensitivity to VPL could not be explained by the gene expression of mdr1 and MRP. It is possible that the changes in the cell membrane and decreased proliferate ability might be attributed to the resistance. Unlike multidrug resistance induced by chemotherapy, VPL may be not an ideal reverser to radioresistant cells. Therefore, the new biological strategy needs to be developed to treat recurring radioresistant tumor in combination with chemotherapy.}, } @article {pmid19472368, year = {2009}, author = {Mikhailov, KV and Konstantinova, AV and Nikitin, MA and Troshin, PV and Rusin, LY and Lyubetsky, VA and Panchin, YV and Mylnikov, AP and Moroz, LL and Kumar, S and Aleoshin, VV}, title = {The origin of Metazoa: a transition from temporal to spatial cell differentiation.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {31}, number = {7}, pages = {758-768}, doi = {10.1002/bies.200800214}, pmid = {19472368}, issn = {1521-1878}, support = {R01 GM097502/GM/NIGMS NIH HHS/United States ; R01 HG002096/HG/NHGRI NIH HHS/United States ; BBSB14418/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation ; Genes ; Life Cycle Stages ; Models, Biological ; Time Factors ; }, abstract = {For over a century, Haeckel's Gastraea theory remained a dominant theory to explain the origin of multicellular animals. According to this theory, the animal ancestor was a blastula-like colony of uniform cells that gradually evolved cell differentiation. Today, however, genes that typically control metazoan development, cell differentiation, cell-to-cell adhesion, and cell-to-matrix adhesion are found in various unicellular relatives of the Metazoa, which suggests the origin of the genetic programs of cell differentiation and adhesion in the root of the Opisthokonta. Multicellular stages occurring in the complex life cycles of opisthokont protists (mesomycetozoeans and choanoflagellates) never resemble a blastula. Here, we discuss a more realistic scenario of transition to multicellularity through integration of pre-existing transient cell types into the body of an early metazoon, which possessed a complex life cycle with a differentiated sedentary filter-feeding trophic stage and a non-feeding blastula-like larva, the synzoospore. Choanoflagellates are considered as forms with secondarily simplified life cycles.}, } @article {pmid19463087, year = {2009}, author = {Lichtenstein, AV}, title = {Carcinogenesis: evolution of concepts.}, journal = {Biochemistry. Biokhimiia}, volume = {74}, number = {4}, pages = {353-361}, doi = {10.1134/s0006297909040014}, pmid = {19463087}, issn = {1608-3040}, mesh = {Animals ; *Biological Evolution ; Humans ; Mutagenesis ; Neoplasms/*etiology/genetics/pathology ; *Neoplastic Processes ; }, abstract = {Cancer is considered as an unintended consequence of internal imperfection of multicellular organisms: Darwinian evolution "does not foresee the future and does not plan for it", it is forced to handle only anything that it has at a given moment "at hand", which makes inevitable compromises and restrictions. In this case, there are a number of founding dogmas including mutagenesis as the main driving force of carcinogenesis; the environment as the main source of mutagenic effects; tumor monoclonality; cancer cell multistage transformation as Darwinian process of successive mutation-selection cycles. Recent discoveries complicate, supplement, and sometimes transform into an opposite fixed concepts. As a result, a new "image" of carcinogenesis is formed as a biological phenomenon whose conservation is indicative of its evolutionary utility.}, } @article {pmid19460306, year = {2009}, author = {Lin, X}, title = {Cryptococcus neoformans: morphogenesis, infection, and evolution.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {9}, number = {4}, pages = {401-416}, doi = {10.1016/j.meegid.2009.01.013}, pmid = {19460306}, issn = {1567-7257}, mesh = {*Biological Evolution ; Cryptococcosis/*microbiology ; *Cryptococcus neoformans/cytology/growth & development/pathogenicity ; Hyphae ; Morphogenesis ; Phenotype ; Pheromones/metabolism ; Virulence ; }, abstract = {Cryptococcus neoformans is the major causative agent of fungal meningoencephalitis in both immunocompromised and immunocompetent individuals. During infection, this fungus is observed in the yeast form and is only occasionally seen as the pseudohyphal or hyphal form (filamentous forms). Early studies suggested that phase transition of C. neoformans from a multi-cellular filamentous form to the unicellular yeast form might be essential for the survival of this fungus in mammalian hosts. However, how different Cryptococcus morphotypes exhibit different levels of pathogenicity in hosts are unclear. This review discusses the possible roles of each form inside and outside of mammalian hosts and summarizes recent insights on the life cycle and morphogenesis of this fungus and their impact on the pathogenicity. Application of recently developed advanced tools for C. neoformans research may assist in understanding the genetic and molecular mechanisms of morphology-associated virulence in this important fungal pathogen. Research on the association between fungal dimorphism and pathogenicity has been traditionally limited to a few related ascomyceteous fungal pathogens. This review is to stimulate discussion and expansion of this type of investigation to a larger group of evolutionary divergent fungi capable of causing systemic fungal infections in humans. Hopefully, a common theme for the convergent evolution of virulence-associated morphology will emerge with future studies.}, } @article {pmid19448332, year = {2009}, author = {Urushihara, H}, title = {The cellular slime mold: eukaryotic model microorganism.}, journal = {Experimental animals}, volume = {58}, number = {2}, pages = {97-104}, doi = {10.1538/expanim.58.97}, pmid = {19448332}, issn = {1881-7122}, mesh = {Animals ; Culture Techniques ; Dictyosteliida/*genetics ; Eukaryotic Cells/*chemistry/physiology ; Genome ; Life Cycle Stages ; *Models, Animal ; Phylogeny ; *Soil Microbiology ; }, abstract = {Cellular slime molds are eukaryotic microorganisms in the soil. They feed on bacteria as solitary amoebae but conditionally construct multicellular forms in which cell differentiation takes place. Therefore, they are attractive for the study of fundamental biological phenomena such as phagocytosis, cell division, chemotactic movements, intercellular communication, cell differentiation, and morphogenesis. The most widely used species, Dictyostelium discoideum, is highly amenable to experimental manipulation and can be used with most recent molecular biological techniques. Its genome and cDNA analyses have been completed and well-annotated data are publicly available. A larger number of orthologues of human disease-related genes were found in D. discoideum than in yeast. Moreover, some pathogenic bacteria infect Dictyostelium amoebae. Thus, this microorganism can also offer a good experimental system for biomedical research. The resources of cellular slime molds, standard strains, mutants, and genes are maintained and distributed upon request by the core center of the National BioResource Project (NBRP-nenkin) to support Dictyostelium community users as well as new users interested in new platforms for research and/or phylogenic consideration.}, } @article {pmid19438897, year = {2009}, author = {Tesei, A and Zoli, W and Arienti, C and Storci, G and Granato, AM and Pasquinelli, G and Valente, S and Orrico, C and Rosetti, M and Vannini, I and Dubini, A and Dell'Amore, D and Amadori, D and Bonafè, M}, title = {Isolation of stem/progenitor cells from normal lung tissue of adult humans.}, journal = {Cell proliferation}, volume = {42}, number = {3}, pages = {298-308}, pmid = {19438897}, issn = {1365-2184}, mesh = {Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Cell Differentiation ; *Cell Separation ; Female ; Humans ; Immunohistochemistry ; Lung/*cytology ; Male ; Mesoderm/cytology ; Microscopy, Electron, Transmission ; Middle Aged ; RNA Interference ; RNA, Small Interfering ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cells/*cytology ; }, abstract = {OBJECTIVES: This study aimed to isolate and characterize stem/progenitor cells, starting from normal airway epithelia, obtained from human adults.

MATERIALS AND METHODS: Cultures of multicellular spheroids were obtained from human lung tissue specimens after mechanical and enzymatic digestion. Tissue-specific markers were detected on their cells by immunohistochemical and immunofluorescent techniques. Ultrastructural morphology of the spheroids (termed as bronchospheres) was evaluated by electron microscopy, gene expression analysis was performed by reverse transcription-polymerase chain reaction, and gene down-regulation was analysed by an RNA interference technique.

RESULTS: Bronchospheres were found to be composed of cells with high expression of stem cell regulatory genes, which was not or was only weakly detectable in original tissues. Morphological analysis showed that bronchospheres were composed of mixed phenotype cells with type II alveolar and Clara cell features, highlighting their airway resident cell origin. In addition to displaying specific pulmonary and epithelial commitment, bronchospheres showed mesenchymal features. Silencing of the Slug gene, known to play a pivotal role in epithelial-mesenchymal transition processes and which was highly expressed in bronchospheres but not in original tissue, led bronchospheres to gain a differentiated bronchial/alveolar phenotype and to lose the stemness gene expression pattern.

CONCLUSIONS: Ours is the first study to describe ex vivo expansion of stem/progenitor cells resident in human lung epithelia, and our results suggest that the epithelial-mesenchymal transition process, still active in a subset of airway cells, may regulate transit of stem/progenitor cells towards epithelial differentiation.}, } @article {pmid19432949, year = {2009}, author = {Leptihn, S and Har, JY and Chen, J and Ho, B and Wohland, T and Ding, JL}, title = {Single molecule resolution of the antimicrobial action of quantum dot-labeled sushi peptide on live bacteria.}, journal = {BMC biology}, volume = {7}, number = {}, pages = {22}, pmid = {19432949}, issn = {1741-7007}, mesh = {Amino Acid Sequence ; Antimicrobial Cationic Peptides/chemistry/*pharmacology ; Bacteriolysis/drug effects ; Cell Membrane/drug effects/metabolism ; Cytosol/drug effects/metabolism ; Diffusion/drug effects ; Escherichia coli/*drug effects/ultrastructure ; Gold ; Green Fluorescent Proteins/metabolism ; Lipopolysaccharides/metabolism ; Microbial Sensitivity Tests ; Molecular Probes/metabolism ; Molecular Sequence Data ; Nanoparticles/ultrastructure ; *Quantum Dots ; Spectrometry, Fluorescence ; *Staining and Labeling ; }, abstract = {BACKGROUND: Antimicrobial peptides are found in all kingdoms of life. During the evolution of multicellular organisms, antimicrobial peptides were established as key elements of innate immunity. Most antimicrobial peptides are thought to work by disrupting the integrity of cell membranes, causing pathogen death. As antimicrobial peptides target the membrane structure, pathogens can only acquire resistance by a fundamental change in membrane composition. Hence, the evolution of pathogen resistance has been a slow process. Therefore antimicrobial peptides are valuable alternatives to classical antibiotics against which multiple drug-resistant bacteria have emerged. For potential therapeutic applications as antibiotics a thorough knowledge of their mechanism of action is essential. Despite the increasingly comprehensive understanding of the biochemical properties of these peptides, the actual mechanism by which antimicrobial peptides lyse microbes is controversial.

RESULTS: Here we investigate how Sushi 1, an antimicrobial peptide derived from the horseshoe crab (Carcinoscorpius rotundicauda), induces lysis of Gram-negative bacteria. To follow the entire process of antimicrobial action, we performed a variety of experiments including transmission electron microscopy and fluorescence correlation spectroscopy as well as single molecule tracking of quantum dot-labeled antimicrobial peptides on live bacteria. Since in vitro measurements do not necessarily correlate with the in vivo action of a peptide we developed a novel fluorescent live bacteria lysis assay. Using fully functional nanoparticle-labeled Sushi 1, we observed the process of antimicrobial action at the single-molecule level.

CONCLUSION: Recently the hypothesis that many antimicrobial peptides act on internal targets to kill the bacterium has been discussed. Here, we demonstrate that the target sites of Sushi 1 are outer and inner membranes and are not cytosolic. Further, our findings suggest four successive steps of the bactericidal process: 1) Binding, mediated mainly by charged residues in the peptide; 2) Peptide association, as peptide concentration increases evidenced by a change in diffusive behavior; 3) Membrane disruption, during which lipopolysaccharide is not released; and 4) Lysis, by leakage of cytosolic content through large membrane defects.}, } @article {pmid19416859, year = {2009}, author = {Bengtson, S and Belivanova, V and Rasmussen, B and Whitehouse, M}, title = {The controversial "Cambrian" fossils of the Vindhyan are real but more than a billion years older.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {106}, number = {19}, pages = {7729-7734}, pmid = {19416859}, issn = {1091-6490}, mesh = {Archaeology/methods ; Biological Evolution ; Cyanobacteria/metabolism ; *Fossils ; Gases ; Geologic Sediments/microbiology ; Paleontology/methods ; Phylogeny ; Time ; }, abstract = {The age of the Vindhyan sedimentary basin in central India is controversial, because geochronology indicating early Proterozoic ages clashes with reports of Cambrian fossils. We present here an integrated paleontologic-geochronologic investigation to resolve this conundrum. New sampling of Lower Vindhyan phosphoritic stromatolitic dolomites from the northern flank of the Vindhyans confirms the presence of fossils most closely resembling those found elsewhere in Cambrian deposits: annulated tubes, embryo-like globules with polygonal surface pattern, and filamentous and coccoidal microbial fabrics similar to Girvanella and Renalcis. None of the fossils, however, can be ascribed to uniquely Cambrian or Ediacaran taxa. Indeed, the embryo-like globules are not interpreted as fossils at all but as former gas bubbles trapped in mucus-rich cyanobacterial mats. Direct dating of the same fossiliferous phosphorite yielded a Pb-Pb isochron of 1,650 +/- 89 (2sigma) million years ago, confirming the Paleoproterozoic age of the fossils. New U-Pb geochronology of zircons from tuffaceous mudrocks in the Lower Vindhyan Porcellanite Formation on the southern flank of the Vindhyans give comparable ages. The Vindhyan phosphorites provide a window of 3-dimensionally preserved Paleoproterozoic fossils resembling filamentous and coccoidal cyanobacteria and filamentous eukaryotic algae, as well as problematic forms. Like Neoproterozoic phosphorites a billion years later, the Vindhyan deposits offer important new insights into the nature and diversity of life, and in particular, the early evolution of multicellular eukaryotes.}, } @article {pmid19416510, year = {2009}, author = {Ros, VI and Hurst, GD}, title = {Lateral gene transfer between prokaryotes and multicellular eukaryotes: ongoing and significant?.}, journal = {BMC biology}, volume = {7}, number = {}, pages = {20}, pmid = {19416510}, issn = {1741-7007}, mesh = {Animals ; Eukaryotic Cells/*cytology/*metabolism ; Gene Transfer, Horizontal/*genetics ; Prokaryotic Cells/*metabolism ; Symbiosis/genetics ; }, abstract = {The expansion of genome sequencing projects has produced accumulating evidence for lateral transfer of genes between prokaryotic and eukaryotic genomes. However, it remains controversial whether these genes are of functional importance in their recipient host. Nikoh and Nakabachi, in a recent paper in BMC Biology, take a first step and show that two genes of bacterial origin are highly expressed in the pea aphid Acyrthosiphon pisum. Active gene expression of transferred genes is supported by three other recent studies. Future studies should reveal whether functional proteins are produced and whether and how these are targeted to the appropriate compartment. We argue that the transfer of genes between host and symbiont may occasionally be of great evolutionary importance, particularly in the evolution of the symbiotic interaction itself.}, } @article {pmid19413690, year = {2009}, author = {Sadras, VO and Denison, RF}, title = {Do plant parts compete for resources? An evolutionary viewpoint.}, journal = {The New phytologist}, volume = {183}, number = {3}, pages = {565-574}, doi = {10.1111/j.1469-8137.2009.02848.x}, pmid = {19413690}, issn = {1469-8137}, mesh = {*Biological Evolution ; *Plant Physiological Phenomena ; Plant Structures/genetics/*physiology ; Plants/genetics ; }, abstract = {Simultaneously growing sinks are thought to compete for plant resources. Negative correlations, for example between grain number and stem mass in cereals, indeed resemble competition; but is the notion of intra-plant competition evolutionarily justified? Here we review intra-plant competition in light of two aspects of evolutionary biology: (a) major transitions that led to the reorganization of evolutionary individuals (e.g. isolated DNA molecules and independent cells) into new units of adaptation (e.g. chromosomes and multicellular organisms) with associated constraints to intra-individual conflict; and (b) genomic conflicts within individual plants with implications for resource allocation. Against this background, we look at apparent competition among genetically identical plant parts, and conclude that plants might use competition-like mechanisms to allocate resources, but only to the extent that these proximate mechanisms enhance overall plant fitness. In dealing with apparent competition among genetically different plant structures, we emphasize developing seeds attached to the same maternal plant, and the determination of yield components in annual crops. We propose that competition-like mechanisms among genetically different plant parts have been strongly shaped by the evolution of genomic conflict between parent and offspring, between female and male parents, and among siblings. By defining the number and potential size of grain simultaneously and before fertilization, a strong maternal control of resource allocation is exerted that favours uniform offspring size and partially counteracts genomic conflict.}, } @article {pmid19413338, year = {2009}, author = {Li, W and Scarlata, S and Miller, WT}, title = {Evidence for convergent evolution in the signaling properties of a choanoflagellate tyrosine kinase.}, journal = {Biochemistry}, volume = {48}, number = {23}, pages = {5180-5186}, pmid = {19413338}, issn = {1520-4995}, support = {CA 58530/CA/NCI NIH HHS/United States ; R01 CA058530-15/CA/NCI NIH HHS/United States ; R01 GM053132/GM/NIGMS NIH HHS/United States ; R01 CA058530/CA/NCI NIH HHS/United States ; GM 053132/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; COS Cells ; Chlorocebus aethiops ; *Evolution, Molecular ; Genes, src ; Phosphorylation ; Protein-Tyrosine Kinases/genetics/*metabolism ; *Signal Transduction ; Spodoptera/metabolism ; Transfection ; }, abstract = {Until recently, phosphotyrosine signaling was thought to be restricted to multicellular animals. Surprisingly, the unicellular choanoflagellate Monosiga brevicollis contains a number and diversity of tyrosine kinases that exceeds that of any metazoan, including humans. Many of these M. brevicollis tyrosine kinases possess combinations of signaling domains that do not occur in metazoans. One such kinase, the Src-like protein MbSrc4, contains a lipid-binding C2 domain N-terminal to the conserved SH3-SH2-kinase domains. Here, we report that the enzyme is highly active as a tyrosine kinase and that the targeting functions of the C2, SH3, and SH2 domains are similar to the mammalian counterparts. The membrane-binding activity of the C2 domain is functionally equivalent to the myristoylation signal of c-Src, suggesting that it is an example of convergent evolution. When expressed in mammalian cells, full-length MbSrc4 displays low activity toward endogenous proteins, and it cannot functionally substitute for mammalian c-Src in a reporter gene assay. Removal of the MbSrc4 C2 domain leads to increased phosphorylation of cellular proteins. Thus, in contrast to the related M. brevicollis Src-like kinase MbSrc1, MbSrc4 is not targeted properly to mammalian Src substrates, suggesting that the C2 domain plays a specific role in M. brevicollis signaling.}, } @article {pmid19412892, year = {2009}, author = {Avramova, Z}, title = {Evolution and pleiotropy of TRITHORAX function in Arabidopsis.}, journal = {The International journal of developmental biology}, volume = {53}, number = {2-3}, pages = {371-381}, doi = {10.1387/ijdb.082664za}, pmid = {19412892}, issn = {1696-3547}, mesh = {Adaptation, Physiological/genetics/physiology ; Arabidopsis/genetics/*physiology ; Arabidopsis Proteins/classification/genetics/*physiology ; *Evolution, Molecular ; Genetic Variation ; Histone-Lysine N-Methyltransferase ; Multigene Family ; Phylogeny ; Promoter Regions, Genetic/genetics ; Signal Transduction/genetics/physiology ; Transcription Factors/classification/genetics/*physiology ; }, abstract = {The SET domain-containing genes of the TRITHORAX family encode epigenetic factors that maintain the expression of targeted genes. Trithorax homologs have been found in both animals and plants. Since these are thought to have evolved multicellularity independently, common mechanisms of epigenetic regulation must be evolutionarily ancient and derived from a common ancestor. In addition, each lineage has evolved unique mechanisms to expand the original repertoire of epigenetic functions. Phylogenetic analysis of SET domain proteins has outlined some intriguing evolutionary trends. In plants, epigenetic gene silencing mechanisms have been aggressively pursued. In contrast, studies of epigenetic mechanisms maintaining active gene expression have been scarce. The goal of this review is to draw attention to this gap. Trithorax function in plants are analyzed here in an evolutionary context tracing phylogenetic relationships between the histone methyltransferase activities in unicellular and multicellular domains of life. The involvement of two members of the Arabidopsis Trithorax family, ARABIDOPSIS HOMOLOG of TRITHORAX1 (ATX1), and ARABIDOPSIS HOMOLOG of TRITHORAX2 (ATX2), in developmental and adaptation processes of the plant is overviewed.}, } @article {pmid19412887, year = {2009}, author = {Brunmeir, R and Lagger, S and Seiser, C}, title = {Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation.}, journal = {The International journal of developmental biology}, volume = {53}, number = {2-3}, pages = {275-289}, doi = {10.1387/ijdb.082649rb}, pmid = {19412887}, issn = {1696-3547}, mesh = {Animals ; Cell Differentiation/genetics/*physiology ; Embryonic Development/genetics/*physiology ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Enzymologic ; Histone Deacetylase 1 ; Histone Deacetylase 2 ; Histone Deacetylases/classification/genetics/*metabolism ; Mice ; Models, Biological ; Phylogeny ; Repressor Proteins/classification/genetics/*metabolism ; }, abstract = {During development from the fertilized egg to a multicellular organism, cell fate decisions have to be taken and cell lineage or tissue-specific gene expression patterns are created and maintained. These alterations in gene expression occur in the context of chromatin structure and are controlled by chromatin modifying enzymes. Gene disruption studies in different genetic systems have shown an essential role of various histone deacetylases (HDACs) during early development and cellular differentiation. In this review, we focus on the functions of the class I enzymes HDAC1 and HDAC2 during development in different organisms and summarise the current knowledge about their involvement in neurogenesis, myogenesis, haematopoiesis and epithelial cell differentiation.}, } @article {pmid19400651, year = {2010}, author = {Gordon, TR and Leveau, JH}, title = {Plant pathology: a story about biology.}, journal = {Annual review of phytopathology}, volume = {48}, number = {}, pages = {293-309}, doi = {10.1146/annurev-phyto-080508-081919}, pmid = {19400651}, issn = {1545-2107}, mesh = {Biology/education ; Career Choice ; Humans ; *Plant Diseases ; }, abstract = {Disease is a universal feature of life for multicellular organisms, and the study of disease has contributed to the establishment of key concepts in the biological sciences. This implies strong connections between plant pathology and basic biology, something that could perhaps be made more apparent to undergraduate students interested in the life sciences. To that end, we present an instructional narrative that begins with a simple question: Why are there diseases? Responses and follow-up questions can facilitate exploration of such topics as the evolution of parasitism, plant adaptations to parasitism, impacts of parasites on native plant communities, and ways in which human intervention can foster the emergence of aggressive plant pathogens. This approach may help to attract students who would not have found their way to plant pathology through traditional pathways. Packaging the narrative as a game may render it more interesting and accessible, particularly to a younger audience.}, } @article {pmid19398025, year = {2009}, author = {Reeb, VC and Peglar, MT and Yoon, HS and Bai, JR and Wu, M and Shiu, P and Grafenberg, JL and Reyes-Prieto, A and Rümmele, SE and Gross, J and Bhattacharya, D}, title = {Interrelationships of chromalveolates within a broadly sampled tree of photosynthetic protists.}, journal = {Molecular phylogenetics and evolution}, volume = {53}, number = {1}, pages = {202-211}, doi = {10.1016/j.ympev.2009.04.012}, pmid = {19398025}, issn = {1095-9513}, mesh = {Cryptophyta/classification/*genetics ; DNA, Algal/genetics ; DNA, Ribosomal/genetics ; Evolution, Molecular ; *Phylogeny ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {The Chromalveolata "supergroup" is a massive assemblage of single-celled and multicellular protists such as ciliates and kelps that remains to be substantiated in molecular trees. Recent multigene analyses place chromalveolates into two major clades, the SAR (Stramenopiles, Alveolata, and Rhizaria) and the Cryptophyta+Haptophyta. Here we determined 69 new sequences from different chromalveolates to study the interrelationships of its constituent phyla. We included in our trees, the novel groups Telonemia and Katablepharidophyta that have previously been described as chromalvoleate allies. The best phylogenetic resolution resulted from a 6-protein (actin, alpha-tubulin, beta-tubulin, cytosolic HSP70, BIP HSP70, HSP90) and a 5-protein (lacking HSP90) alignment that validated the SAR and cryptophyte+haptophyte clades with the inclusion of telonemids in the former and katablepharids in the latter. We assessed the Plastidophila hypothesis that is based on EF2 data and suggest this grouping may be explained by horizontal gene transfers involving the EF2 gene rather than indicating host relationships.}, } @article {pmid19396969, year = {2009}, author = {Mamkaev, IuV}, title = {[The phylogenetic role of ontogenies (recapitulation and morphogenesis)].}, journal = {Izvestiia Akademii nauk. Seriia biologicheskaia}, volume = {}, number = {2}, pages = {134-142}, pmid = {19396969}, issn = {1026-3470}, mesh = {Animals ; Annelida/anatomy & histology/cytology ; Body Patterning/physiology ; Morphogenesis/*physiology ; *Phylogeny ; Turbellaria/anatomy & histology/cytology ; }, abstract = {Different approaches to evolutionary interpretation of ontogenies are compared, with special emphasis on the evolutionary role of morphogenetic mechanisms (construction technologies) substantially affecting the structure of definitive forms: they largely determine the structural characteristics of organs, types of anatomical and histological systems, and specificity of symmetry of organisms and their parts. The role of cellular morphogenesis inherited from protozoic ancestors in the morphogenesis of multicellular organisms is demonstrated. Two main ways of improving morphogeneses are considered, based on epithelial morphogenesis and early determined few-celled primordial. On the one hand, the phylogenetic role of archallaxes and deviations is emphasized, these events often switching evolution to a fundamentally new direction. On the other hand, many characteristics of developmental stages are explainable by rationalization of morphogeneses and do not recapitulate ancestral forms, which should be taken into consideration in phylogenetic interpretation of embryogeneses; in particular, this applies to interpretation of axial relationships.}, } @article {pmid19395676, year = {2009}, author = {Vilanova, E and Coutinho, CC and Mourão, PA}, title = {Sulfated polysaccharides from marine sponges (Porifera): an ancestor cell-cell adhesion event based on the carbohydrate-carbohydrate interaction.}, journal = {Glycobiology}, volume = {19}, number = {8}, pages = {860-867}, doi = {10.1093/glycob/cwp059}, pmid = {19395676}, issn = {1460-2423}, mesh = {Animals ; Cell Adhesion ; In Vitro Techniques ; Polysaccharides/*metabolism ; Porifera/*cytology/metabolism ; }, abstract = {Marine sponges (Porifera) are ancient and simple eumetazoans. They constitute key organisms in the evolution from unicellular to multicellular animals. We now demonstrated that pure sulfated polysaccharides from marine sponges are responsible for the species-specific cell-cell interaction in these invertebrates. This conclusion was based on the following observations: (1) each species of marine sponge has a single population of sulfated polysaccharide, which differ among the species in their sugar composition and sulfate content; (2) sulfated polysaccharides from sponge interact with each other in a species-specific way, as indicated by an affinity chromatography assay, and this interaction requires calcium; (3) homologous, but not heterologous, sulfated polysaccharide inhibits aggregation of dissociated sponge cells; (4) we also observed a parallel between synthesis of the sulfated polysaccharide and formation of large aggregates of sponge cells, known as primmorphs. Once aggregation reached a plateau, the demand for the de novo synthesis of sulfated polysaccharides ceased. Heparin can mimic the homologous sulfated polysaccharide on the in vitro interaction and also as an inhibitor of aggregation of the dissociated sponge cells. However, this observation is not relevant for the biology of the sponge since heparin is not found in the invertebrate. In conclusion, marine sponges display an ancestor event of cell-cell adhesion, based on the calcium-dependent carbohydrate-carbohydrate interaction.}, } @article {pmid19378259, year = {2009}, author = {Newman, SA and Bhat, R}, title = {Dynamical patterning modules: a "pattern language" for development and evolution of multicellular form.}, journal = {The International journal of developmental biology}, volume = {53}, number = {5-6}, pages = {693-705}, doi = {10.1387/ijdb.072481sn}, pmid = {19378259}, issn = {1696-3547}, mesh = {Animals ; Biological Evolution ; *Body Patterning ; Cell Adhesion ; Developmental Biology/methods ; Elasticity ; Epithelium/pathology ; Mesoderm/pathology ; *Models, Biological ; Morphogenesis ; Oscillometry ; Phenotype ; Time Factors ; }, abstract = {This article considers the role played by a core set of "dynamical patterning modules" (DPMs) in the origination, development and evolution of complex organisms. These consist of the products of a subset of the genes of what has come to be known as the "developmental-genetic toolkit" in association with physical processes they mobilize. The physical processes are those characteristic of chemically and mechanically excitable mesoscopic systems like cell aggregates: cohesion, viscoelasticity, diffusion, spatiotemporal heterogeneity based on activator-inhibitor interaction, and multistable and oscillatory dynamics. We focus on the emergence of the Metazoa, and show how toolkit gene products and pathways that pre-existed the metazoans acquired novel morphogenetic functions simply by virtue of the change in scale and context inherent to multicellularity. We propose that DPMs, acting singly and in combination with each other, constitute a "pattern language" capable of generating all metazoan body plans and organ forms. This concept implies that the multicellular organisms of the late Precambrian-early Cambrian were phenotypically plastic, fluently exploring morphospace in a fashion decoupled from both function-based selection and genotypic change. The relatively stable developmental trajectories and morphological phenotypes of modern organisms, then, are considered to be products of stabilizing selection. This perspective solves the apparent "molecular homology-analogy paradox," whereby widely divergent modern animal types utilize the same molecular toolkit during development, but it does so by inverting the neo-Darwinian principle that phenotypic disparity was generated over long periods of time in concert with, and in proportion to genotypic change.}, } @article {pmid19369262, year = {2009}, author = {Acquisti, C and Kumar, S and Elser, JJ}, title = {Signatures of nitrogen limitation in the elemental composition of the proteins involved in the metabolic apparatus.}, journal = {Proceedings. Biological sciences}, volume = {276}, number = {1667}, pages = {2605-2610}, pmid = {19369262}, issn = {0962-8452}, mesh = {Animals ; Arabidopsis/genetics/metabolism ; Drosophila melanogaster/metabolism ; Gene Expression Regulation/*physiology ; Humans ; Metabolism ; Mice ; Nitrogen/*metabolism ; Proteins/*chemistry/*metabolism ; }, abstract = {Nitrogen (N) is a fundamental component of nucleotides and amino acids and is often a limiting nutrient in natural ecosystems. Thus, study of the N content of biomolecules may establish important connections between ecology and genomics. However, while significant differences in the elemental composition of whole organisms are well documented, how the flux of nutrients in the cell has shaped the evolution of different cellular processes remains poorly understood. By examining the elemental composition of major functional classes of proteins in four multicellular eukaryotic model organisms, we find that the catabolic machinery shows substantially lower N content than the anabolic machinery and the rest of the proteome. This pattern suggests that ecological selection for N conservation specifically targets cellular components that are highly expressed in response to nutrient limitation. We propose that the RNA component of the anabolic machineries is the mechanistic force driving the elemental imbalance we found, and that RNA functions as an intracellular nutrient reservoir that is degraded and recycled during starvation periods. A comparison of the elemental composition of the anabolic and catabolic machineries in species that have experienced different levels of N limitation in their evolutionary history (animals versus plants) suggests that selection for N conservation has preferentially targeted the catabolic machineries of plants, resulting in a lower N content of the proteins involved in their catabolic processes. These findings link the composition of major cellular components to the environmental factors that trigger the activation of those components, suggesting that resource availability has constrained the atomic composition and the molecular architecture of the biotic processes that enable cells to respond to reduced nutrient availability.}, } @article {pmid19364817, year = {2009}, author = {Swat, A and Dolado, I and Rojas, JM and Nebreda, AR}, title = {Cell density-dependent inhibition of epidermal growth factor receptor signaling by p38alpha mitogen-activated protein kinase via Sprouty2 downregulation.}, journal = {Molecular and cellular biology}, volume = {29}, number = {12}, pages = {3332-3343}, pmid = {19364817}, issn = {1098-5549}, mesh = {Animals ; Base Sequence ; Cell Count ; Cell Cycle/physiology ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Neoplastic ; Cells, Cultured ; Contact Inhibition/*physiology ; Cyclin-Dependent Kinase Inhibitor p27/deficiency/genetics/metabolism ; DNA Primers/genetics ; Down-Regulation ; ErbB Receptors/*metabolism ; Female ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; MAP Kinase Signaling System ; Membrane Proteins ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinase 14/deficiency/*metabolism ; Models, Biological ; NIH 3T3 Cells ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; }, abstract = {Contact inhibition is a fundamental process in multicellular organisms aimed at inhibiting proliferation at high cellular densities through poorly characterized intracellular signals, despite availability of growth factors. We have previously identified the protein kinase p38alpha as a novel regulator of contact inhibition, as p38alpha is activated upon cell-cell contacts and p38alpha-deficient cells are impaired in both confluence-induced proliferation arrest and p27(Kip1) accumulation. Here, we establish that p27(Kip1) plays a key role downstream of p38alpha to arrest proliferation at high cellular densities. Surprisingly, p38alpha does not directly regulate p27(Kip1) expression levels but leads indirectly to confluent upregulation of p27(Kip1) and cell cycle arrest via the inhibition of mitogenic signals originating from the epidermal growth factor receptor (EGFR). Hence, confluent activation of p38alpha uncouples cell proliferation from mitogenic stimulation by inducing EGFR degradation through downregulation of the EGFR-stabilizing protein Sprouty2 (Spry2). Accordingly, confluent p38alpha-deficient cells fail to downregulate Spry2, providing them in turn with sustained EGFR signaling that facilitates cell overgrowth and oncogenic transformation. Our results provide novel mechanistic insight into the role of p38alpha as a sensor of cell density, which induces confluent cell cycle arrest via the Spry2-EGFR-p27(Kip1) network.}, } @article {pmid19364083, year = {2009}, author = {Cacciapaglia, F and Spadaccio, C and Chello, M and Gigante, A and Coccia, R and Afeltra, A and Amoroso, A}, title = {Apoptotic molecular mechanisms implicated in autoimmune diseases.}, journal = {European review for medical and pharmacological sciences}, volume = {13}, number = {1}, pages = {23-40}, pmid = {19364083}, issn = {1128-3602}, mesh = {Aging/immunology ; Animals ; Apoptosis/*immunology/*physiology ; Autoantigens/physiology ; Autoimmune Diseases/*etiology/metabolism/pathology ; Humans ; Phagocytosis ; Self Tolerance ; }, abstract = {Apoptosis is a programmed cell death that represents a normal component of the development, differentiation and health of multicellular organisms leading to an adequate cellular turnover and homeostasis. In autoimmune diseases, the immune system recognizes various autoantigens causing damage in target organs. Dead cells represent an important source of autoantigens that, in particular conditions, can represent a stimulus for an autoimmune response. A large number of studies reported the impairment of the apoptosis regulatory mechanisms in immune cells as a pivotal element in the pathogenesis and evolution of autoimmune disorders. Several pathogenetic pathways have been claimed to account for autoimmunity development during apoptotic processes. In fact, interestingly abnormalities potentially leading to immune disorders have been described as occurring in each step involved in apoptosis, from the very beginning to the post death phenomena. In this extent we propose a systematic review of the molecular mechanisms strictly leading to apoptosis with particular interest to their alterations, potentially causing tissue specific and/or systemic autoimmunity.}, } @article {pmid19360093, year = {2009}, author = {Giurumescu, CA and Sternberg, PW and Asthagiri, AR}, title = {Predicting phenotypic diversity and the underlying quantitative molecular transitions.}, journal = {PLoS computational biology}, volume = {5}, number = {4}, pages = {e1000354}, pmid = {19360093}, issn = {1553-7358}, support = {T32 GM007616/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Caenorhabditis elegans/classification/*physiology ; Caenorhabditis elegans Proteins/*classification/*physiology ; Computer Simulation ; Female ; Gene Expression Regulation, Developmental/*physiology ; *Models, Biological ; Phenotype ; Signal Transduction/*physiology ; Species Specificity ; Vulva/*physiology ; }, abstract = {During development, signaling networks control the formation of multicellular patterns. To what extent quantitative fluctuations in these complex networks may affect multicellular phenotype remains unclear. Here, we describe a computational approach to predict and analyze the phenotypic diversity that is accessible to a developmental signaling network. Applying this framework to vulval development in C. elegans, we demonstrate that quantitative changes in the regulatory network can render approximately 500 multicellular phenotypes. This phenotypic capacity is an order-of-magnitude below the theoretical upper limit for this system but yet is large enough to demonstrate that the system is not restricted to a select few outcomes. Using metrics to gauge the robustness of these phenotypes to parameter perturbations, we identify a select subset of novel phenotypes that are the most promising for experimental validation. In addition, our model calculations provide a layout of these phenotypes in network parameter space. Analyzing this landscape of multicellular phenotypes yielded two significant insights. First, we show that experimentally well-established mutant phenotypes may be rendered using non-canonical network perturbations. Second, we show that the predicted multicellular patterns include not only those observed in C. elegans, but also those occurring exclusively in other species of the Caenorhabditis genus. This result demonstrates that quantitative diversification of a common regulatory network is indeed demonstrably sufficient to generate the phenotypic differences observed across three major species within the Caenorhabditis genus. Using our computational framework, we systematically identify the quantitative changes that may have occurred in the regulatory network during the evolution of these species. Our model predictions show that significant phenotypic diversity may be sampled through quantitative variations in the regulatory network without overhauling the core network architecture. Furthermore, by comparing the predicted landscape of phenotypes to multicellular patterns that have been experimentally observed across multiple species, we systematically trace the quantitative regulatory changes that may have occurred during the evolution of the Caenorhabditis genus.}, } @article {pmid19359578, year = {2009}, author = {Engler, AJ and Humbert, PO and Wehrle-Haller, B and Weaver, VM}, title = {Multiscale modeling of form and function.}, journal = {Science (New York, N.Y.)}, volume = {324}, number = {5924}, pages = {208-212}, pmid = {19359578}, issn = {1095-9203}, support = {R01 CA078731/CA/NCI NIH HHS/United States ; R01-CA078731/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Cell Adhesion/*physiology ; Cell Aggregation/physiology ; Cell Communication ; Extracellular Matrix/*physiology ; Genotype ; Homeostasis ; Morphogenesis/*physiology ; Phenotype ; Proteins/chemistry/*physiology ; Signal Transduction/*physiology ; }, abstract = {Topobiology posits that morphogenesis is driven by differential adhesive interactions among heterogeneous cell populations. This paradigm has been revised to include force-dependent molecular switches, cell and tissue tension, and reciprocal interactions with the microenvironment. It is now appreciated that tissue development is executed through conserved decision-making modules that operate on multiple length scales from the molecular and subcellular level through to the cell and tissue level and that these regulatory mechanisms specify cell and tissue fate by modifying the context of cellular signaling and gene expression. Here, we discuss the origin of these decision-making modules and illustrate how emergent properties of adhesion-directed multicellular structures sculpt the tissue, promote its functionality, and maintain its homeostasis through spatial segregation and organization of anchored proteins and secreted factors and through emergent properties of tissues, including tension fields and energy optimization.}, } @article {pmid19100909, year = {2008}, author = {Hall, MN}, title = {mTOR-what does it do?.}, journal = {Transplantation proceedings}, volume = {40}, number = {10 Suppl}, pages = {S5-8}, doi = {10.1016/j.transproceed.2008.10.009}, pmid = {19100909}, issn = {0041-1345}, mesh = {Animals ; Cell Division/physiology ; Cell Physiological Phenomena ; Growth Substances/physiology ; Homeostasis ; Humans ; Mammals ; Mechanistic Target of Rapamycin Complex 1 ; Multiprotein Complexes ; Phosphatidylinositol 3-Kinases/*metabolism ; Protein Kinases/*physiology ; Proteins ; Signal Transduction ; TOR Serine-Threonine Kinases ; Transcription Factors/physiology ; }, abstract = {Target of rapamycin (TOR) is a highly conserved serine/threonine kinase that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy, and stress. TOR, which was originally discovered in yeast, is conserved in all eukaryotes including plants, worms, flies, and mammals. The discovery of TOR led to a fundamental change in how we think about cell growth. It is not a spontaneous process that just happens when building blocks (nutrients) are available, but rather a highly regulated, plastic process controlled by TOR-dependent signaling pathways. TOR is found in 2 structurally and functionally distinct multiprotein complexes, TORC1 and TORC2. The 2 TOR complexes, like TOR itself, are highly conserved. Mammalian TORC1 (mTORC1) is rapamycin sensitive and contains mTOR, raptor, and mLST8. TORC1 in yeast and mammals mediates temporal control of cell growth by regulating several cellular processes, including translation, transcription, ribosome biogenesis, nutrient transport, and autophagy. mTORC2 is rapamycin insensitive and contains mTOR, rictor, mSIN1, PRR5, and mLST8. TORC2 in yeast and mammals mediates spatial control of cell growth by regulating the actin cytoskeleton. Thus, the 2 TOR complexes constitute an ancestral signaling network conserved throughout eukaryotic evolution to control the fundamental process of cell growth. As a central controller of cell growth, TOR plays a key role in development and aging and has been implicated in disorders such as cancer, cardiovascular disease, obesity, and diabetes. The challenge now is to understand the role of mTOR signaling to coordinate and integrate overall body growth in multicellular organisms.}, } @article {pmid19343174, year = {2009}, author = {Lucas, J and Bilzer, A and Moll, L and Zündorf, I and Dingermann, T and Eichinger, L and Siol, O and Winckler, T}, title = {The carboxy-terminal domain of Dictyostelium C-module-binding factor is an independent gene regulatory entity.}, journal = {PloS one}, volume = {4}, number = {4}, pages = {e5012}, pmid = {19343174}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; DNA-Binding Proteins/chemistry/genetics/*physiology ; Dictyostelium/genetics/*metabolism ; Gene Expression Regulation/*physiology ; Genetic Complementation Test ; Oligonucleotide Array Sequence Analysis ; Protozoan Proteins/chemistry/genetics/*physiology ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {The C-module-binding factor (CbfA) is a multidomain protein that belongs to the family of jumonji-type (JmjC) transcription regulators. In the social amoeba Dictyostelium discoideum, CbfA regulates gene expression during the unicellular growth phase and multicellular development. CbfA and a related D. discoideum CbfA-like protein, CbfB, share a paralogous domain arrangement that includes the JmjC domain, presumably a chromatin-remodeling activity, and two zinc finger-like (ZF) motifs. On the other hand, the CbfA and CbfB proteins have completely different carboxy-terminal domains, suggesting that the plasticity of such domains may have contributed to the adaptation of the CbfA-like transcription factors to the rapid genome evolution in the dictyostelid clade. To support this hypothesis we performed DNA microarray and real-time RT-PCR measurements and found that CbfA regulates at least 160 genes during the vegetative growth of D. discoideum cells. Functional annotation of these genes revealed that CbfA predominantly controls the expression of gene products involved in housekeeping functions, such as carbohydrate, purine nucleoside/nucleotide, and amino acid metabolism. The CbfA protein displays two different mechanisms of gene regulation. The expression of one set of CbfA-dependent genes requires at least the JmjC/ZF domain of the CbfA protein and thus may depend on chromatin modulation. Regulation of the larger group of genes, however, does not depend on the entire CbfA protein and requires only the carboxy-terminal domain of CbfA (CbfA-CTD). An AT-hook motif located in CbfA-CTD, which is known to mediate DNA binding to A+T-rich sequences in vitro, contributed to CbfA-CTD-dependent gene regulatory functions in vivo.}, } @article {pmid20525580, year = {2009}, author = {Schoch, CL and Sung, GH and López-Giráldez, F and Townsend, JP and Miadlikowska, J and Hofstetter, V and Robbertse, B and Matheny, PB and Kauff, F and Wang, Z and Gueidan, C and Andrie, RM and Trippe, K and Ciufetti, LM and Wynns, A and Fraker, E and Hodkinson, BP and Bonito, G and Groenewald, JZ and Arzanlou, M and de Hoog, GS and Crous, PW and Hewitt, D and Pfister, DH and Peterson, K and Gryzenhout, M and Wingfield, MJ and Aptroot, A and Suh, SO and Blackwell, M and Hillis, DM and Griffith, GW and Castlebury, LA and Rossman, AY and Lumbsch, HT and Lücking, R and Büdel, B and Rauhut, A and Diederich, P and Ertz, D and Geiser, DM and Hosaka, K and Inderbitzin, P and Kohlmeyer, J and Volkmann-Kohlmeyer, B and Mostert, L and O'Donnell, K and Sipman, H and Rogers, JD and Shoemaker, RA and Sugiyama, J and Summerbell, RC and Untereiner, W and Johnston, PR and Stenroos, S and Zuccaro, A and Dyer, PS and Crittenden, PD and Cole, MS and Hansen, K and Trappe, JM and Yahr, R and Lutzoni, F and Spatafora, JW}, title = {The Ascomycota tree of life: a phylum-wide phylogeny clarifies the origin and evolution of fundamental reproductive and ecological traits.}, journal = {Systematic biology}, volume = {58}, number = {2}, pages = {224-239}, doi = {10.1093/sysbio/syp020}, pmid = {20525580}, issn = {1076-836X}, mesh = {Ascomycota/classification/cytology/*genetics ; Ecosystem ; Genes, Fungal ; *Phylogeny ; Reproduction ; }, abstract = {We present a 6-gene, 420-species maximum-likelihood phylogeny of Ascomycota, the largest phylum of Fungi. This analysis is the most taxonomically complete to date with species sampled from all 15 currently circumscribed classes. A number of superclass-level nodes that have previously evaded resolution and were unnamed in classifications of the Fungi are resolved for the first time. Based on the 6-gene phylogeny we conducted a phylogenetic informativeness analysis of all 6 genes and a series of ancestral character state reconstructions that focused on morphology of sporocarps, ascus dehiscence, and evolution of nutritional modes and ecologies. A gene-by-gene assessment of phylogenetic informativeness yielded higher levels of informativeness for protein genes (RPB1, RPB2, and TEF1) as compared with the ribosomal genes, which have been the standard bearer in fungal systematics. Our reconstruction of sporocarp characters is consistent with 2 origins for multicellular sexual reproductive structures in Ascomycota, once in the common ancestor of Pezizomycotina and once in the common ancestor of Neolectomycetes. This first report of dual origins of ascomycete sporocarps highlights the complicated nature of assessing homology of morphological traits across Fungi. Furthermore, ancestral reconstruction supports an open sporocarp with an exposed hymenium (apothecium) as the primitive morphology for Pezizomycotina with multiple derivations of the partially (perithecia) or completely enclosed (cleistothecia) sporocarps. Ascus dehiscence is most informative at the class level within Pezizomycotina with most superclass nodes reconstructed equivocally. Character-state reconstructions support a terrestrial, saprobic ecology as ancestral. In contrast to previous studies, these analyses support multiple origins of lichenization events with the loss of lichenization as less frequent and limited to terminal, closely related species.}, } @article {pmid19334005, year = {2009}, author = {Delattre, M and Félix, MA}, title = {The evolutionary context of robust and redundant cell biological mechanisms.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {31}, number = {5}, pages = {537-545}, doi = {10.1002/bies.200800215}, pmid = {19334005}, issn = {1521-1878}, mesh = {*Biological Evolution ; *Cell Physiological Phenomena ; Cells/cytology/metabolism ; Models, Biological ; Spindle Apparatus/metabolism ; }, abstract = {The robustness of biological processes to perturbations has so far been mainly explored in unicellular organisms; multicellular organisms have been studied for developmental processes or in the special case of redundancy between gene duplicates. Here we explore the robustness of cell biological mechanisms of multicellular organisms in an evolutionary context. We propose that the reuse of similar cell biological mechanisms in different cell types of the same organism has evolutionary implications: (1) the maintenance of apparently redundant mechanisms over evolutionary time may in part be explained by their differential requirement in various cell types; (2) the relative requirement for two alternative mechanisms may evolve among homologous cells in different organisms. We present examples of cell biological processes, such as centrosome separation in prophase, spindle formation or cleavage furrow positioning, that support the first proposition. We propose experimental tests of these hypotheses.}, } @article {pmid19330799, year = {2009}, author = {Coffman, JA}, title = {Is Runx a linchpin for developmental signaling in metazoans?.}, journal = {Journal of cellular biochemistry}, volume = {107}, number = {2}, pages = {194-202}, pmid = {19330799}, issn = {1097-4644}, support = {R01 GM070840/GM/NIGMS NIH HHS/United States ; R01 GM070840-06/GM/NIGMS NIH HHS/United States ; GM070840/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/physiology ; Cell Proliferation ; Core Binding Factor alpha Subunits/*physiology ; *Gene Expression Regulation, Developmental ; Humans ; Signal Transduction/*physiology ; }, abstract = {The Runt domain (Runx) is a 128 amino acid sequence motif that defines a metazoan family of sequence-specific DNA binding proteins, which appears to have originated in concert with the intercellular signaling systems that coordinate multicellular development in animals. In the model organisms where they have been studied (fruit fly, mouse, sea urchin, and nematode) Runx genes are essential for normal development, and in humans they are causally associated with a variety of cancers, manifesting both oncogenic and tumor suppressive attributes. During development Runx proteins support both cell proliferation and differentiation, and function in both transcriptional activation and repression. Runx function is thus context-dependent, with the context provided genetically by cis-regulatory sequence architecture and epigenetically by development. This context dependency makes it difficult to formulate reductionistic generalizations concerning Runx function in normal and carcinogenic development. However, a growing body of literature links Runx function to each of the major intercellular signaling systems in animals, suggesting that the general function of Runx transcription factors may be to potentiate and govern genomic responsiveness to developmental signaling.}, } @article {pmid19304937, year = {2009}, author = {Kandasamy, MK and McKinney, EC and Meagher, RB}, title = {A single vegetative actin isovariant overexpressed under the control of multiple regulatory sequences is sufficient for normal Arabidopsis development.}, journal = {The Plant cell}, volume = {21}, number = {3}, pages = {701-718}, pmid = {19304937}, issn = {1040-4651}, support = {R01 GM036397/GM/NIGMS NIH HHS/United States ; GM36397/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/classification/genetics/*metabolism ; Arabidopsis/anatomy & histology/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; *Gene Expression Regulation, Plant ; Genetic Complementation Test ; Molecular Sequence Data ; Morphogenesis ; Mutation ; Phenotype ; Phylogeny ; Plant Roots/physiology/ultrastructure ; Plants, Genetically Modified ; Protein Isoforms/classification/genetics/*metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; *Regulatory Sequences, Nucleic Acid ; }, abstract = {The relative significance of gene regulation and protein isovariant differences remains unexplored for most gene families, particularly those participating in multicellular development. Arabidopsis thaliana encodes three vegetative actins, ACT2, ACT7, and ACT8, in two ancient and highly divergent subclasses. Mutations in any of these differentially expressed actins revealed only mild phenotypes. However, double mutants were extremely dwarfed, with altered cell and organ morphology and an aberrant F-actin cytoskeleton (e.g., act2-1 act7-4 and act8-2 act7-4) or totally root-hairless (e.g., act2-1 act8-2). Our studies suggest that the three vegetative actin genes and protein isovariants play distinct subclass-specific roles during plant morphogenesis. For example, during root development, ACT7 was involved in root growth, epidermal cell specification, cell division, and root architecture, and ACT2 and ACT8 were essential for root hair tip growth. Also, genetic complementation revealed that the ACT2 and ACT8 isovariants, but not ACT7, fully rescued the root hair growth defects of single and double mutants. Moreover, we synthesized fully normal plants overexpressing the ACT8 isovariant from multiple actin regulatory sequences as the only vegetative actin in the act2-1 act7-4 background. In summary, it is evident that differences in vegetative actin gene regulation and the diversity in actin isovariant sequences are essential for normal plant development.}, } @article {pmid19302539, year = {2009}, author = {Váchová, L and Chernyavskiy, O and Strachotová, D and Bianchini, P and Burdíková, Z and Fercíková, I and Kubínová, L and Palková, Z}, title = {Architecture of developing multicellular yeast colony: spatio-temporal expression of Ato1p ammonium exporter.}, journal = {Environmental microbiology}, volume = {11}, number = {7}, pages = {1866-1877}, doi = {10.1111/j.1462-2920.2009.01911.x}, pmid = {19302539}, issn = {1462-2920}, support = {55005623//Howard Hughes Medical Institute/United States ; }, mesh = {*Gene Expression Regulation, Fungal ; Green Fluorescent Proteins/genetics/metabolism ; Membrane Transport Proteins/*biosynthesis ; Microscopy, Confocal/methods ; Recombinant Fusion Proteins/genetics/metabolism ; Saccharomyces cerevisiae/*enzymology/*growth & development ; Saccharomyces cerevisiae Proteins/*biosynthesis ; Staining and Labeling/methods ; Time Factors ; }, abstract = {Yeasts, when growing on solid surfaces, form organized multicellular structures, colonies, in which cells differentiate and thus possess different functions and undergo dissimilar fate. Understanding the principles involved in the formation of these structures requires new approaches that allow the study of individual cells directly in situ without needing to remove them from the microbial community. Here we introduced a new approach to the analysis of whole yeast microcolonies either containing specific proteins labelled by fluorescent proteins or stained with specific dyes, by two-photon excitation confocal microscopy. It revealed that the colonies are covered with a thin protective skin-like surface cell layer which blocks penetration of harmful compounds. The cells forming the layer are tightly connected via cell walls, the presence of which is essential for keeping of protective layer function. Viewing the colonies from different angles allowed us to reconstruct a three-dimensional profile of the cells producing ammonium exporter Ato1p within developing microcolonies growing either as individuals or within a group of microcolonies. We show that neighbouring microcolonies coordinate production of Ato1p-GFP. Ato1p itself appears synchronously in cells, which do not originate from the same ancestor, but occupy specific position within the colony.}, } @article {pmid19289080, year = {2009}, author = {Wu, MY and Hill, CS}, title = {Tgf-beta superfamily signaling in embryonic development and homeostasis.}, journal = {Developmental cell}, volume = {16}, number = {3}, pages = {329-343}, doi = {10.1016/j.devcel.2009.02.012}, pmid = {19289080}, issn = {1878-1551}, support = {//Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Body Patterning/physiology ; Embryonic Development/*physiology ; Gastrulation/physiology ; Germ Layers/embryology ; Homeostasis/*physiology ; Humans ; Ligands ; Models, Biological ; Receptors, Transforming Growth Factor beta/physiology ; Signal Transduction ; Smad Proteins/physiology ; Transforming Growth Factor beta/*physiology ; }, abstract = {TGF-beta superfamily signaling pathways emerged with the evolution of multicellular animals, suggesting that these pathways contribute to the increased diversity and complexity required for the development and homeostasis of these organisms. In this review we begin by exploring some key developmental and disease processes requiring TGF-beta ligands to underscore the fundamental importance of these pathways before delving into the molecular mechanism of signal transduction, focusing on recent findings. Finally, we discuss how these ligands act as morphogens, how their activity and signaling range is regulated, and how they interact with other signaling pathways to achieve their specific and varied functional roles.}, } @article {pmid19285746, year = {2009}, author = {Makino, T and Hokamp, K and McLysaght, A}, title = {The complex relationship of gene duplication and essentiality.}, journal = {Trends in genetics : TIG}, volume = {25}, number = {4}, pages = {152-155}, doi = {10.1016/j.tig.2009.03.001}, pmid = {19285746}, issn = {0168-9525}, mesh = {Animals ; Computational Biology ; Databases, Genetic ; Drosophila/*genetics ; Evolution, Molecular ; Fungi/genetics ; Gene Dosage ; *Gene Duplication ; Genome ; Mice ; Models, Biological ; *Models, Genetic ; Models, Statistical ; Phenotype ; Species Specificity ; }, abstract = {In yeast and worm, duplicate genes overlap in function so that deleting one of a pair from the genome is less likely to be lethal than deleting a singleton gene. By contrast, previous analyses showed that mouse duplicate genes were as essential as singletons. We show that the relationship between gene duplication and essentiality is complex in multicellular organisms, with developmental genes and genes that were duplicated by whole genome duplication being more essential than other duplicated genes.}, } @article {pmid19281950, year = {2009}, author = {Lopez, P and Bapteste, E}, title = {Molecular phylogeny: reconstructing the forest.}, journal = {Comptes rendus biologies}, volume = {332}, number = {2-3}, pages = {171-182}, doi = {10.1016/j.crvi.2008.07.003}, pmid = {19281950}, issn = {1768-3238}, mesh = {*Evolution, Molecular ; Gene Transfer, Horizontal ; Phylogeny ; Trees/*physiology ; }, abstract = {Phylogeny, be it morphological or molecular, has long tried to explain the extant biodiversity by the Tree of Species, which is a logical consequence of strict Darwinian evolutionary principles. Through constant improvement of both methods and data sets, some parts of this diversity have actually been demonstrated to be the result of a tree-like process. For some other parts, and especially for prokaryotes, different molecular markers have, however, produced different evolutionary trees, preventing the reconstruction of such a Tree. While technical artifacts could be blamed for these discrepancies, Lateral Gene Transfers are now largely held for responsible, and their existence requires an extension of the Darwinian framework, since genetic material is not always vertically inherited from parents to offspring. Through a variety of biological processes, sometimes large parts of DNA are exchanged between phylogenetically distant contemporary organisms, especially between those sharing the same environment. While mainly concerning prokaryotes, Lateral Gene Transfers have been also demonstrated to affect eukaryotes, and even multicellular ones, like plants or animals. Most of the time, these transfers allow important adaptations and the colonisation of new niches. The quantitative and qualitative importance of genetic transfers has thus severely challenged the very existence of a universal Tree of Species, since genetic connections, at least for microbes, seem more reticulated than tree-like. Even traditional biological concepts, like the concept of species, need to be re-evaluated in the light of recent discoveries. In short, instead of focusing on a elusive universal tree, biologists are now considering the whole forest corresponding to the multiple processes of inheritance, both vertical and horizontal. This constitutes the major challenge of evolutionary biology for the years to come.}, } @article {pmid19280701, year = {2008}, author = {Chai, CL and Zhang, Z and Huang, FF and Wang, XY and Yu, QY and Liu, BB and Tian, T and Xia, QY and Lu, C and Xiang, ZH}, title = {A genomewide survey of homeobox genes and identification of novel structure of the Hox cluster in the silkworm, Bombyx mori.}, journal = {Insect biochemistry and molecular biology}, volume = {38}, number = {12}, pages = {1111-1120}, doi = {10.1016/j.ibmb.2008.06.008}, pmid = {19280701}, issn = {1879-0240}, mesh = {Amino Acid Sequence ; Animals ; Bombyx/*genetics ; Gene Expression Profiling ; Gene Expression Regulation/physiology ; *Genes, Homeobox ; Genes, Insect ; *Genome, Insect ; Insect Proteins/genetics/metabolism ; Molecular Sequence Data ; *Multigene Family ; Phylogeny ; }, abstract = {Homeobox genes encode transcriptional factors that play crucial roles in a variety of developmental pathways from unicellular to multicellular eukaryotes. We have identified 102 homeobox genes in the typical insect of Lepidoptera, Bombyx mori, based on the newly assembled genome sequence with 9X coverage. These identified homeobox genes were categorized into nine classes including at least 74 families. The available ESTs and microarray data at present confirmed that more than half of them were expressed during silkworm developmental processes. Orthologs of pb, zen and ftz were newly identified in the Bombyx Hox cluster on chromosome 6. Interestingly, a special group of 12 tandemly duplicated homeobox genes was found located between Bmpb and Bmzen in the Bombyx Hox cluster, suggesting that Hox cluster might have experienced a lineage-specific expansion in the silkworm. A detailed analysis on genome data reveals that a split exists between Bmlab and Bmpb. Our data provide valuable information for future research on the development and evolution of silkworm.}, } @article {pmid19273190, year = {2009}, author = {Bazellieres, E and Assemat, E and Arsanto, JP and Le Bivic, A and Massey-Harroche, D}, title = {Crumbs proteins in epithelial morphogenesis.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {14}, number = {6}, pages = {2149-2169}, doi = {10.2741/3368}, pmid = {19273190}, issn = {2768-6698}, mesh = {Amino Acid Sequence ; Animals ; Eye Proteins/chemistry/*physiology ; Humans ; Membrane Proteins/chemistry/*physiology ; Molecular Sequence Data ; *Morphogenesis ; Nerve Tissue Proteins/chemistry/*physiology ; Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {Cell polarity is an essential feature of most eukaryotic cells, especially epithelial cells in multicellular animals. Polarity protein complexes that regulate epithelial organization have been identified. In this review, it is proposed to describe how the Crumbs complex acts in the process of cell polarity and epithelial organization. During the last decade, several partners of Crumbs, an apical transmembrane protein, have been identified and their direct or indirect associations with the cytoplasmic domain of Crumbs have been dissected. In addition, mutants of several of the genes encoding proteins belonging to the Crumbs network have been obtained in animals ranging from flies to mouse, which have led to a better understanding of their functions in vivo. These functions include polarity axis formation, stabilization of epithelial apico-lateral junctions, photoreceptor organization and ciliogenesis. Since human CRUMBS1 mutations are associated with retina degeneration, it has become essential to define Crumbs network and to understand exactly how this network acts in polarized cells, with a view to developing suitable therapeutic approaches for treating this severe degenerative disease.}, } @article {pmid19269027, year = {2009}, author = {Babister, JC and Hails, LA and Oreffo, RO and Davis, SA and Mann, S}, title = {The effect of pre-coating human bone marrow stromal cells with hydroxyapatite/amino acid nanoconjugates on osteogenesis.}, journal = {Biomaterials}, volume = {30}, number = {18}, pages = {3174-3182}, doi = {10.1016/j.biomaterials.2009.02.024}, pmid = {19269027}, issn = {1878-5905}, mesh = {Alanine/*pharmacology ; Alkaline Phosphatase/analysis ; Animals ; Arginine/*pharmacology ; Cell Culture Techniques/*instrumentation ; Cell Survival ; Cells, Cultured/physiology ; Durapatite/*pharmacology ; Humans ; Implants, Experimental ; Mice ; Mice, Nude ; *Nanocomposites ; Oligopeptides/*pharmacology ; Osteocalcin/analysis ; Osteogenesis/*drug effects ; Polymerase Chain Reaction ; RNA/analysis ; Stromal Cells/*physiology ; }, abstract = {Aqueous colloidal suspensions of positively charged, amino acid-functionalized hydroxyapatite (HAp) nanoparticles (HAp/alanine and HAp/arginine) were added to a HBMSC suspension to effect non-specific cell surface deposition due to favourable attractive electrostatic interactions. Subsequent maintenance of these hybrid precursors under in vitro basal (non-osteogenic) culture conditions for up to 21 days, either as a monolayer or as a 3D pellet culture system, resulted in significantly increased levels of markers of osteoblast differentiation in comparison with uncoated cells. In monolayer culture, osteogenic activity could be further enhanced in a dose-dependent manner by surface derivatization of the amino acid-stabilized nanoparticles with the cell surface-specific binding peptide arginine-glycine-aspartic acid (RGD). Significantly, in 3D pellet culture conditions all HAp nanoconjugates promoted osteoblast differentiation, whereas for uncoated cells even soluble osteogenic culture additives were ineffectual. We therefore tested these constructs for in vivo activity by subcutaneous implantation in immunocompromised mice. New osteoid formation was observed in samples recovered after 21 days, comparable to the extensive areas of mineralized extracellular matrix produced in vitro. Overall, these studies outline the potential of biomolecular/hydroxyapatite nanoconjugates to promote osteogenic cell differentiation in vitro and hence provide new models to examine skeletal cell differentiation and function. Moreover, the pre-coating of HBMSCs enables the formation of viable hybrid multicellular 3D constructs with demonstrable activity both in vitro and in vivo.}, } @article {pmid19251990, year = {2009}, author = {Tompkins-Macdonald, GJ and Gallin, WJ and Sakarya, O and Degnan, B and Leys, SP and Boland, LM}, title = {Expression of a poriferan potassium channel: insights into the evolution of ion channels in metazoans.}, journal = {The Journal of experimental biology}, volume = {212}, number = {Pt 6}, pages = {761-767}, pmid = {19251990}, issn = {0022-0949}, mesh = {Amino Acid Sequence ; Animals ; Barium/metabolism ; Base Sequence ; Bee Venoms/pharmacology ; *Biological Evolution ; Cesium/metabolism ; Electrophysiology ; Gene Expression Regulation/*physiology ; Ion Transport/drug effects ; Molecular Sequence Data ; Porifera/genetics/*metabolism ; Potassium/metabolism ; Potassium Channels, Inwardly Rectifying/chemistry/*genetics/*metabolism ; }, abstract = {Ion channels establish and regulate membrane potentials in excitable and non-excitable cells. How functional diversification of ion channels contributed to the evolution of nervous systems may be understood by studying organisms at key positions in the evolution of animal multicellularity. We have carried out the first analysis of ion channels cloned from a marine sponge, Amphimedon queenslandica. Phylogenetic comparison of sequences encoding for poriferan inward-rectifier K(+) (Kir) channels suggests that Kir channels from sponges, cnidarians and triploblastic metazoans each arose from a single channel and that duplications arose independently in the different groups. In Xenopus oocytes, AmqKirA and AmqKirB produced K(+) currents with strong inward rectification, as seen in the mammalian Kir2 channels, which are found in excitable cells. The pore properties of AmqKir channels demonstrated strong K(+) selectivity and block by Cs(+) and Ba(2+). We present an original analysis of sponge ion channel physiology and an examination of the phylogenetic relationships of this channel with other cloned Kir channels.}, } @article {pmid19247599, year = {2009}, author = {Misevic, GN and Karamanos, Y and Misevic, NJ}, title = {Atomic force microscopy measurements of intermolecular binding forces.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {522}, number = {}, pages = {143-150}, doi = {10.1007/978-1-59745-413-1_8}, pmid = {19247599}, issn = {1064-3745}, mesh = {Biotechnology ; Carbohydrates/chemistry ; Microscopy, Atomic Force/*methods ; Microscopy, Electron, Scanning Transmission ; Nanotechnology ; }, abstract = {Atomic force microscopy (AFM) measurements of intermolecular binding strength between a single pair of complementary cell adhesion molecules in physiological solutions provided the first quantitative evidence for their cohesive function. This novel AFM-based nanobiotechnology opens a molecular mechanic approach for studying structure- to function-related properties of any type of individual biological macromolecules. The presented example of Porifera cell adhesion glyconectin proteoglycans showed that homotypic carbohydrate to carbohydrate interactions between two primordial proteoglycans can hold the weight of 1,600 cells. Thus, glyconectin type carbohydrates, as the most peripheral cell surface molecules of sponges (today's simplest living Metazoa), are proposed to be the primary cell adhesive molecules essential for the evolution of the multicellularity.}, } @article {pmid19245552, year = {2009}, author = {Torday, JS and Ihida-Stansbury, K and Rehan, VK}, title = {Leptin stimulates Xenopus lung development: evolution in a dish.}, journal = {Evolution & development}, volume = {11}, number = {2}, pages = {219-224}, doi = {10.1111/j.1525-142X.2009.00321.x}, pmid = {19245552}, issn = {1525-142X}, support = {HL055268/HL/NHLBI NIH HHS/United States ; HL075405/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Basement Membrane/metabolism ; Choline/metabolism ; Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Gene Regulatory Networks/drug effects ; Leptin/*metabolism/pharmacology ; Locomotion ; Lung/*embryology ; Microscopy, Electron, Transmission/methods ; Models, Biological ; Pulmonary Gas Exchange ; Respiration ; Surface-Active Agents ; Xenopus laevis/*embryology ; }, abstract = {The transition from uni- to multicellular organisms required metabolic cooperativity through cell-cell interactions mediated by soluble growth factors. We have empirically demonstrated such an integrating mechanism by which the metabolic hormone leptin stimulates lung development, causing the thinning of the gas exchange surface and the obligate increase in lung surfactant synthesis. All of these processes have occurred both phylogenetically and developmentally during the course of vertebrate lung evolution from fish to man. Here we show the integrating effects of the environmentally sensitive, pleiotropic hormone leptin on the development of the Xenopus laevis tadpole lung. The process described in this study provides a mechanistically integrated link between the metabolic regulatory hormone leptin and its manifold downstream effects on a wide variety of physiologic structures and functions, including locomotion and respiration, the cornerstones of land vertebrate evolution. It provides physiologic selection pressure at multiple levels to progressively generate Gene Regulatory Networks both within and between organs, from cells to systems. This model provides a cipher for understanding the evolution of complex physiology.}, } @article {pmid19243489, year = {2009}, author = {Archetti, M}, title = {Survival of the steepest: hypersensitivity to mutations as an adaptation to soft selection.}, journal = {Journal of evolutionary biology}, volume = {22}, number = {4}, pages = {740-750}, doi = {10.1111/j.1420-9101.2009.01697.x}, pmid = {19243489}, issn = {1420-9101}, mesh = {Adaptation, Biological/*genetics ; Animals ; Computer Simulation ; *Models, Genetic ; Mutation/*genetics ; *Selection, Genetic ; }, abstract = {Darwinian evolution favours genotypes with high fitness ('survival of the fittest'). Models of quasi-species evolution, however, suggest that in some cases selection may favour genotypes that are more robust against the impact of mutations ('survival of the flattest') even if these genotypes have lower fitness. I show that the opposite effect will be observed if competition occurs during development (e.g. among embryos or ovules) or before the adult phase (e.g. among the progeny of an individual). If viability is not affected by selection at these initial stages (soft selection), the genotypes that are more sensitive to the effects of mutations may increase in frequency because they get rid more easily of deleterious mutations. In a simple theoretical model of mutation and selection, genotypes located in steeper regions of the fitness surface are favoured ('survival of the steepest') even if they do not have higher viability, and even if they have slightly deleterious effects. Hypersensitive genes are potentially harmful for the individual, but with soft selection during the juvenile phase they persist in the genome because they reduce competition with their mutants. Soft selection occurs in practically all vascular plants and in many animals, therefore antirobustness may be a very common feature of the genome of multicellular organisms.}, } @article {pmid19243224, year = {2009}, author = {Gordon, AJ and Halliday, JA and Blankschien, MD and Burns, PA and Yatagai, F and Herman, C}, title = {Transcriptional infidelity promotes heritable phenotypic change in a bistable gene network.}, journal = {PLoS biology}, volume = {7}, number = {2}, pages = {e44}, pmid = {19243224}, issn = {1545-7885}, mesh = {DNA-Directed RNA Polymerases/metabolism ; Epigenesis, Genetic ; Escherichia coli/*genetics/metabolism ; Feedback, Physiological ; *Gene Expression Regulation, Bacterial ; *Gene Regulatory Networks ; Genes, Switch ; Lac Operon/genetics ; Phenotype ; Protein Multimerization ; Stochastic Processes ; *Transcription, Genetic ; }, abstract = {Bistable epigenetic switches are fundamental for cell fate determination in unicellular and multicellular organisms. Regulatory proteins associated with bistable switches are often present in low numbers and subject to molecular noise. It is becoming clear that noise in gene expression can influence cell fate. Although the origins and consequences of noise have been studied, the stochastic and transient nature of RNA errors during transcription has not been considered in the origin or modeling of noise nor has the capacity for such transient errors in information transfer to generate heritable phenotypic change been discussed. We used a classic bistable memory module to monitor and capture transient RNA errors: the lac operon of Escherichia coli comprises an autocatalytic positive feedback loop producing a heritable all-or-none epigenetic switch that is sensitive to molecular noise. Using single-cell analysis, we show that the frequency of epigenetic switching from one expression state to the other is increased when the fidelity of RNA transcription is decreased due to error-prone RNA polymerases or to the absence of auxiliary RNA fidelity factors GreA and GreB (functional analogues of eukaryotic TFIIS). Therefore, transcription infidelity contributes to molecular noise and can effect heritable phenotypic change in genetically identical cells in the same environment. Whereas DNA errors allow genetic space to be explored, RNA errors may allow epigenetic or expression space to be sampled. Thus, RNA infidelity should also be considered in the heritable origin of altered or aberrant cell behaviour.}, } @article {pmid19226299, year = {2009}, author = {Zielinski, FU and Pernthaler, A and Duperron, S and Raggi, L and Giere, O and Borowski, C and Dubilier, N}, title = {Widespread occurrence of an intranuclear bacterial parasite in vent and seep bathymodiolin mussels.}, journal = {Environmental microbiology}, volume = {11}, number = {5}, pages = {1150-1167}, doi = {10.1111/j.1462-2920.2008.01847.x}, pmid = {19226299}, issn = {1462-2920}, mesh = {Animals ; Atlantic Ocean ; Cell Nucleus/*microbiology ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Gammaproteobacteria/*classification/genetics/*isolation & purification/physiology ; In Situ Hybridization, Fluorescence ; Microscopy, Electron, Transmission ; Models, Biological ; Molecular Sequence Data ; Mytilidae/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; }, abstract = {Many parasitic bacteria live in the cytoplasm of multicellular animals, but only a few are known to regularly invade their nuclei. In this study, we describe the novel bacterial parasite "Candidatus Endonucleobacter bathymodioli" that invades the nuclei of deep-sea bathymodiolin mussels from hydrothermal vents and cold seeps. Bathymodiolin mussels are well known for their symbiotic associations with sulfur- and methane-oxidizing bacteria. In contrast, the parasitic bacteria of vent and seep animals have received little attention despite their potential importance for deep-sea ecosystems. We first discovered the intranuclear parasite "Ca. E. bathymodioli" in Bathymodiolus puteoserpentis from the Logatchev hydrothermal vent field on the Mid-Atlantic Ridge. Using primers and probes specific to "Ca. E. bathymodioli" we found this intranuclear parasite in at least six other bathymodiolin species from vents and seeps around the world. Fluorescence in situ hybridization and transmission electron microscopy analyses of the developmental cycle of "Ca. E. bathymodioli" showed that the infection of a nucleus begins with a single rod-shaped bacterium which grows to an unseptated filament of up to 20 microm length and then divides repeatedly until the nucleus is filled with up to 80,000 bacteria. The greatly swollen nucleus destroys its host cell and the bacteria are released after the nuclear membrane bursts. Intriguingly, the only nuclei that were never infected by "Ca. E. bathymodioli" were those of the gill bacteriocytes. These cells contain the symbiotic sulfur- and methane-oxidizing bacteria, suggesting that the mussel symbionts can protect their host nuclei against the parasite. Phylogenetic analyses showed that the "Ca. E. bathymodioli" belongs to a monophyletic clade of Gammaproteobacteria associated with marine metazoans as diverse as sponges, corals, bivalves, gastropods, echinoderms, ascidians and fish. We hypothesize that many of the sequences from this clade originated from intranuclear bacteria, and that these are widespread in marine invertebrates.}, } @article {pmid19223580, year = {2009}, author = {Herron, MD and Hackett, JD and Aylward, FO and Michod, RE}, title = {Triassic origin and early radiation of multicellular volvocine algae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {106}, number = {9}, pages = {3254-3258}, pmid = {19223580}, issn = {1091-6490}, mesh = {*Phylogeny ; Time Factors ; Volvox/*genetics/*radiation effects ; }, abstract = {Evolutionary transitions in individuality (ETIs) underlie the watershed events in the history of life on Earth, including the origins of cells, eukaryotes, plants, animals, and fungi. Each of these events constitutes an increase in the level of complexity, as groups of individuals become individuals in their own right. Among the best-studied ETIs is the origin of multicellularity in the green alga Volvox, a model system for the evolution of multicellularity and cellular differentiation. Since its divergence from unicellular ancestors, Volvox has evolved into a highly integrated multicellular organism with cellular specialization, a complex developmental program, and a high degree of coordination among cells. Remarkably, all of these changes were previously thought to have occurred in the last 50-75 million years. Here we estimate divergence times using a multigene data set with multiple fossil calibrations and use these estimates to infer the times of developmental changes relevant to the evolution of multicellularity. Our results show that Volvox diverged from unicellular ancestors at least 200 million years ago. Two key innovations resulting from an early cycle of cooperation, conflict and conflict mediation led to a rapid integration and radiation of multicellular forms in this group. This is the only ETI for which a detailed timeline has been established, but multilevel selection theory predicts that similar changes must have occurred during other ETIs.}, } @article {pmid19220395, year = {2009}, author = {Wenter, R and Wanner, G and Schüler, D and Overmann, J}, title = {Ultrastructure, tactic behaviour and potential for sulfate reduction of a novel multicellular magnetotactic prokaryote from North Sea sediments.}, journal = {Environmental microbiology}, volume = {11}, number = {6}, pages = {1493-1505}, doi = {10.1111/j.1462-2920.2009.01877.x}, pmid = {19220395}, issn = {1462-2920}, mesh = {Base Sequence ; *Chemotaxis ; Deltaproteobacteria/*classification/*physiology/ultrastructure ; Geologic Sediments/*microbiology ; Iron/metabolism ; Magnetics ; Molecular Sequence Data ; North Sea ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sulfates/*metabolism ; }, abstract = {Multicellular magnetotactic prokaryotes (MMPs) represent highly organized, spherical and motile aggregates of 10-40 bacterial cells containing magnetosomes. Although consisting of different cells, each with its own magnetosomes and flagellation, MMPs orient themselves within a magnetic field and exhibit magnetotaxis. So far, MMPs have only been found in several North and South American coastal lagoons and salt marshes. In the present study, a novel type of MMP was discovered in coastal tidal sand flats of the North Sea. High-resolution scanning electron microscopy revealed the presence of bullet-shaped magnetosomes which were aligned in several parallel chains. Within each aggregate, the magnetosome chains of individual cells were oriented in the same direction. Energy dispersive X-ray (EDX) analysis showed that the magnetosomes are composed of iron sulfide. This particular morphology and arrangement of magnetosomes has previously not been reported for other MMPs. 16S rRNA gene sequence analysis revealed a single phylotype which represented a novel phylogenetic lineage with >or= 4% sequence divergence to all previously described MMP sequences and was related to the dissimilatory sulfate-reducing Desulfosarcina variabilis within the family Desulfobacteraceae of the subphylum Deltaproteobacteria. Fluorescence in situ hybridization with a specific oligonucleotide probe revealed that all MMPs in the tidal flat sediments studied belonged to the novel phylotype. Within each MMP, all bacterial cells showed a hybridization signal, indicating that the aggregates are composed of cells of the same phylotype. Genes for dissimilatory sulfite reductase (dsrAB) and dissimilatory adenosine-5'-phosphate reductase (aprA) could be detected in purified MMP samples, suggesting that MMPs are capable of sulfate reduction. Chemotaxis assays with 41 different test compounds yielded strong responses towards acetate and propionate, whereas other organic acids, alcohols, sugars, sugar alcohols or sulfide did not elicit any response. By means of its coordinated magnetotaxis and chemotaxis, the novel type of MMP is well adapted to the steep chemical gradients which are characteristic for intertidal marine sediments.}, } @article {pmid19209812, year = {2008}, author = {Schevzov, G and O'Neill, G}, title = {Tropomyosin gene expression in vivo and in vitro.}, journal = {Advances in experimental medicine and biology}, volume = {644}, number = {}, pages = {43-59}, pmid = {19209812}, issn = {0065-2598}, mesh = {Alternative Splicing ; Animals ; Cell Differentiation ; Exons ; Gene Expression ; Gene Expression Profiling ; *Gene Expression Regulation ; Humans ; In Vitro Techniques ; Lens, Crystalline/physiology ; Models, Biological ; Muscles/metabolism ; Protein Biosynthesis ; Protein Isoforms ; Tropomyosin/*biosynthesis/chemistry/*genetics ; }, abstract = {The evolution from unicellular to multicellular organisms of increasing complexity is paralleled by increased numbers of tropomyosin (Tm) genes and increasing numbers ofisoforms encoded by each gene. The regulation of Tm isoform expression is intimately associated with the morphological changes that take place during development and cell differentiation. The tissue- and cell-specific Tm expression patterns are regulated at multiple levels, allowing precise spatial and temporal regulation of Tm expression. In this chapter, we review the Tm isoform expression pattern during differentiation of different tissue types and from this data infer some general principles regarding Tm expression patterns during differentiation. Finally, we review the mechanisms that account for the highly regulated repertoire ofTm isoform expression.}, } @article {pmid19209377, year = {2009}, author = {Nedelcu, AM}, title = {Comparative genomics of phylogenetically diverse unicellular eukaryotes provide new insights into the genetic basis for the evolution of the programmed cell death machinery.}, journal = {Journal of molecular evolution}, volume = {68}, number = {3}, pages = {256-268}, pmid = {19209377}, issn = {1432-1432}, mesh = {Amino Acid Sequence ; Animals ; Apoptosis Regulatory Proteins/*genetics ; Databases, Protein ; Eukaryotic Cells ; *Evolution, Molecular ; Fungi/genetics ; Genomics ; Molecular Sequence Data ; *Phylogeny ; Plants/genetics ; }, abstract = {Programmed cell death (PCD) represents a significant component of normal growth and development in multicellular organisms. Recently, PCD-like processes have been reported in single-celled eukaryotes, implying that some components of the PCD machinery existed early in eukaryotic evolution. This study provides a comparative analysis of PCD-related sequences across more than 50 unicellular genera from four eukaryotic supergroups: Unikonts, Excavata, Chromalveolata, and Plantae. A complex set of PCD-related sequences that correspond to domains or proteins associated with all main functional classes--from ligands and receptors to executors of PCD--was found in many unicellular lineages. Several PCD domains and proteins previously thought to be restricted to animals or land plants are also present in unicellular species. Noteworthy, the yeast, Saccharomyces cerevisiae--used as an experimental model system for PCD research, has a rather reduced set of PCD-related sequences relative to other unicellular species. The phylogenetic distribution of the PCD-related sequences identified in unicellular lineages suggests that the genetic basis for the evolution of the complex PCD machinery present in extant multicellular lineages has been established early in the evolution of eukaryotes. The shaping of the PCD machinery in multicellular lineages involved the duplication, co-option, recruitment, and shuffling of domains already present in their unicellular ancestors.}, } @article {pmid19201587, year = {2009}, author = {Anton-Erxleben, F and Thomas, A and Wittlieb, J and Fraune, S and Bosch, TC}, title = {Plasticity of epithelial cell shape in response to upstream signals: a whole-organism study using transgenic Hydra.}, journal = {Zoology (Jena, Germany)}, volume = {112}, number = {3}, pages = {185-194}, doi = {10.1016/j.zool.2008.09.002}, pmid = {19201587}, issn = {0944-2006}, mesh = {Adaptation, Physiological/physiology ; Animals ; Cell Shape/physiology ; Cytoskeleton/metabolism ; Epithelial Cells/*cytology ; Gene Expression Regulation ; Hydra/*cytology/*genetics ; Organisms, Genetically Modified ; Signal Transduction ; Wnt Proteins/metabolism ; }, abstract = {Multicellular organisms consist of a variety of cells of distinctive morphology, with the cell shapes often reproduced with astonishing accuracy between individuals and across species. The morphology of cells varies with tissues, and cell shape changes are of profound importance in many occasions of morphogenesis. To elucidate the mechanisms of cell shape determination and regulation is therefore an important issue. One of the simplest multicellular organisms is the freshwater polyp Hydra. Although much is known about patterning in this early branching metazoan, there is currently little understanding of how cells in Hydra regulate their shape in response to upstream signals. We previously reported generation of transgenic Hydra to trace cells and to study cell behavior in vivo in an animal at the basis of animal evolution. Here, we use a novel transgenic line which expresses enhanced green fluorescent protein (eGFP) specifically in the ectodermal epithelial cells to analyze the structure and shape of epithelial cells as they are recruited into specific regions along the body column and respond to upstream signals such as components of the canonical Wnt signaling pathway. As a general theme, in contrast to epithelial cells in more complex animals, ectodermal epithelial cells in Hydra are capable of drastic changes in structure, shape, and cell contact along the body column. The remarkable phenotypic plasticity of epithelial cells in response to positional signals allows Hydra to build its body with only a limited number of different cell types.}, } @article {pmid19200360, year = {2009}, author = {de Souza, DJ and Bézier, A and Depoix, D and Drezen, JM and Lenoir, A}, title = {Blochmannia endosymbionts improve colony growth and immune defence in the ant Camponotus fellah.}, journal = {BMC microbiology}, volume = {9}, number = {}, pages = {29}, pmid = {19200360}, issn = {1471-2180}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Ants/*immunology/*microbiology/physiology ; DNA, Bacterial/genetics ; Enterobacteriaceae/drug effects/genetics/*physiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Symbiosis ; }, abstract = {BACKGROUND: Microorganisms are a large and diverse form of life. Many of them live in association with large multicellular organisms, developing symbiotic relations with the host and some have even evolved to form obligate endosymbiosis. All Carpenter ants (genus Camponotus) studied hitherto harbour primary endosymbiotic bacteria of the Blochmannia genus. The role of these bacteria in ant nutrition has been demonstrated but the omnivorous diet of these ants lead us to hypothesize that the bacteria might provide additional advantages to their host. In this study, we establish links between Blochmannia, growth of starting new colonies and the host immune response.

RESULTS: We manipulated the number of bacterial endosymbionts in incipient laboratory-reared colonies of Camponotus fellah by administrating doses of an antibiotic (Rifampin) mixed in honey-solution. Efficiency of the treatment was estimated by quantitative polymerase chain reaction and Fluorescent in situ hybridization (FISH), using Blochmannia specific primers (qPCR) and two fluorescent probes (one for all Eubacterial and other specific for Blochmannia). Very few or no bacteria could be detected in treated ants. Incipient Rifampin treated colonies had significantly lower numbers of brood and adult workers than control colonies. The immune response of ants from control and treated colonies was estimated by inserting nylon filaments in the gaster and removing it after 24 h. In the control colonies, the encapsulation response was positively correlated to the bacterial amount, while no correlation was observed in treated colonies. Indeed, antibiotic treatment increased the encapsulation response of the workers, probably due to stress conditions.

CONCLUSION: The increased growth rate observed in non-treated colonies confirms the importance of Blochmannia in this phase of colony development. This would provide an important selective advantage during colony founding, where the colonies are faced with severe inter and intraspecific competition. Furthermore, the bacteria improve the workers encapsulation response. Thus, these ants are likely to be less susceptible to various pathogen attacks, such as the Phoridae fly parasitoids, normally found in the vicinity of Camponotus nests. These advantages might explain the remarkable ecological success of this ant genus, comprising more than 1000 species.}, } @article {pmid19198773, year = {2009}, author = {Müller, WE and Wang, X and Schröder, HC}, title = {Paleoclimate and evolution: emergence of sponges during the neoproterozoic.}, journal = {Progress in molecular and subcellular biology}, volume = {47}, number = {}, pages = {55-77}, doi = {10.1007/978-3-540-88552-8_3}, pmid = {19198773}, issn = {0079-6484}, mesh = {Animals ; *Biological Evolution ; Body Patterning/physiology ; *Climate ; Ecosystem ; Fossils ; Marine Biology ; Porifera/cytology/*physiology ; Stem Cells ; }, abstract = {In the last 15 years, we had to cope with many technological and conceptual obstacles. The major hindrance was the view that sponges are primitive and exist separated from the other metazoan organisms. After answering these problems, the painful scientific process to position the most enigmatic metazoan phylum, the Porifera, into the correct phylogenetic place among the eukaryotes in general and the multicellular animals in particular came to an end. The well-studied taxon Porifera (sponges) was first grouped to the animal-plants or plant-animals, then to the Zoophyta or Mesozoa, and finally to the Parazoa. Only by the application of molecular biological techniques was it possible to place the Porifera monophyletically with the other metazoan phyla, justifying a unification of all multicellular animals to only one kingdom, the Metazoa. The first strong support came from the discovery that cell-cell and cell-matrix adhesion molecules, that were cloned from sponges (mainly the demosponges Suberites domuncula and Geodia cydonium) and that were subsequently expressed, share high DNA sequence and protein function similarity with the corresponding molecules of other metazoans. Together with the molecular biological studies and with the use of the cell culture technologies (primmorphs), which allowed an insight into the stem cell system of these simple organisms, it was possible to stethoscope back in the paleontological history of animals. These studies confirmed the view that the sponges evolved between two epochal ice times, 710-680 Ma (Sturtian glaciation) and 605-585 Ma (Varanger-Marinoan ice age), a period which allowed evolution to proceed but resulted also in a mass extinction of most animal taxa, with the exception of the Porifera. These animals could develop in the aqueous milieu which was rich in silica, due also to their ability to live in a symbiosis with unicellular organisms (prokaryotic and also eukaryotic). Those organisms provided the sponges with the nutrition to survive and to overcome the food deprivation in cold water and even in an environment under the ice. Based on the diverse genetic toolkit, the sponges could also resist the adverse temperature and sunlight climatic influences. It is fortunate that the sponges survived the last 800 million years with their basic body plan. This fact might qualify the sponges to become model organisms not only in biology and molecular biology but also to be used - as living fossils - as reference organisms to deduce important and new insights in the understanding of fossil records explored from the Neoproterozoic. Taken together, these data caused a paradigmatic change; the Porifera are complex and simple, but by far not primitive, and they contribute to the understanding of the deep evolution of animals in molecular biological and paleontological views.}, } @article {pmid19168567, year = {2009}, author = {Szöllosi, GJ and Derényi, I}, title = {Congruent evolution of genetic and environmental robustness in micro-RNA.}, journal = {Molecular biology and evolution}, volume = {26}, number = {4}, pages = {867-874}, doi = {10.1093/molbev/msp008}, pmid = {19168567}, issn = {1537-1719}, mesh = {Animals ; *Evolution, Molecular ; Humans ; MicroRNAs/*genetics ; Models, Genetic ; Selection, Genetic ; }, abstract = {Genetic robustness, the preservation of an optimal phenotype in the face of mutations, is critical to the understanding of evolution as phenotypically expressed genetic variation is the fuel of natural selection. The origin of genetic robustness, whether it evolves directly by natural selection or it is a correlated byproduct of other phenotypic traits, is, however, unresolved. Examining micro-RNA (miRNA) genes of several eukaryotic species, Borenstein and Ruppin (Borenstein E, Ruppin E. 2006. Direct evolution of genetic robustness in microRNA. Proc Natl Acad Sci USA. 103: 6593) showed that the structure of miRNA precursor stem loops exhibits significantly increased mutational robustness in comparison with a sample of random RNA sequences with the same stem-loop structure. The observed robustness was found to be uncorrelated with traditional measures of environmental robustness-implying that miRNA sequences show evidence of the direct evolution of genetic robustness. These findings are surprising as theoretical results indicate that the direct evolution of robustness requires high mutation rates and/or large effective population sizes only found among RNA viruses, not multicellular eukaryotes. We demonstrate that the sampling method used by Borenstein and Ruppin introduced significant bias that lead to an overestimation of robustness. Introducing a novel measure of environmental robustness based on the equilibrium thermodynamic ensemble of secondary structures of the miRNA precursor sequences, we demonstrate that the biophysics of RNA folding induces a high level of correlation between genetic (mutational) and environmental (thermodynamic) robustness, as expected from the theory of plastogenetic congruence introduced by Ancel and Fontana (Ancel LW, Fontana W. 2000. Plasticity, evolvability, and modularity in RNA. J Exp Zool. 288: 242-283). In light of theoretical considerations, we believe that this correlation strongly suggests that genetic robustness observed in miRNA sequences is the byproduct of selection for environmental robustness.}, } @article {pmid19161977, year = {2009}, author = {Johnson, MS and Lu, N and Denessiouk, K and Heino, J and Gullberg, D}, title = {Integrins during evolution: evolutionary trees and model organisms.}, journal = {Biochimica et biophysica acta}, volume = {1788}, number = {4}, pages = {779-789}, doi = {10.1016/j.bbamem.2008.12.013}, pmid = {19161977}, issn = {0006-3002}, mesh = {Animals ; Cell Adhesion/genetics/physiology ; Drosophila melanogaster ; *Evolution, Molecular ; Humans ; Integrin alpha Chains/genetics ; Integrins/*genetics/*physiology ; Mice ; Models, Animal ; Muscle, Skeletal/physiology ; Receptors, Collagen/chemistry ; }, abstract = {The integrins form a large family of cell adhesion receptors. All multicellular animals express integrins, indicating that the family evolved relatively early in the history of metazoans, and homologous sequences of the component domains of integrin alpha and beta subunits are seen in prokaryotes. Some integrins, however, seem to be much younger. For example, the alphaI domain containing integrins, including collagen receptors and leukocyte integrins, have been found in chordates only. Here, we will discuss what conclusions can be drawn about integrin function by studying the evolutionary conservation of integrins. We will also look at how studying integrins in organisms such as the fruit fly and mouse has helped our understanding of integrin evolution-function relationships. As an illustration of this, we will summarize the current understanding of integrin involvement in skeletal muscle formation.}, } @article {pmid19159343, year = {2009}, author = {Broughton, S and Partridge, L}, title = {Insulin/IGF-like signalling, the central nervous system and aging.}, journal = {The Biochemical journal}, volume = {418}, number = {1}, pages = {1-12}, doi = {10.1042/BJ20082102}, pmid = {19159343}, issn = {1470-8728}, support = {066750/A/01/Z//PHS HHS/United States ; }, mesh = {Aging/*physiology ; Animals ; Central Nervous System/*metabolism ; Humans ; Insulin/*metabolism ; Models, Biological ; *Signal Transduction ; Somatomedins/*metabolism ; }, abstract = {Enormous strides in understanding aging have come from the discovery that mutations in single genes can extend healthy life-span in laboratory model organisms such as the yeast Saccharomyces, the fruit fly Drosophila melanogaster, the nematode worm Caenorhabditis elegans and the mouse. IIS [insulin/IGF (insulin-like growth factor)-like signalling] stands out as an important, evolutionarily conserved pathway involved in the determination of lifespan. The pathway has diverse functions in multicellular organisms, and mutations in IIS can affect growth, development, metabolic homoeostasis, fecundity and stress resistance, as well as lifespan. The pleiotropic nature of the pathway and the often negative effects of its disruption mean that the extent, tissue and timing of IIS manipulations are determinants of a positive effect on lifespan. One tissue of particular importance for lifespan extension in diverse organisms is the CNS (central nervous system). Although lowered IIS in the CNS can extend lifespan, IIS is also widely recognized as being neuroprotective and important for growth and survival of neurons. In the present review, we discuss our current understanding of the role of the nervous system in extension of lifespan by altered IIS, and the role of IIS in determination of neuronal function during aging. The nervous system can play both endocrine and cell-autonomous roles in extension of lifespan by IIS, and the effects of IIS on lifespan and neuronal function can be uncoupled to some extent. Tissue-specific manipulation of IIS and the cellular defence mechanisms that it regulates will better define the ways in which IIS affects neuronal and whole-organism function during aging.}, } @article {pmid19156527, year = {2009}, author = {McIntire, CR and Yeretssian, G and Saleh, M}, title = {Inflammasomes in infection and inflammation.}, journal = {Apoptosis : an international journal on programmed cell death}, volume = {14}, number = {4}, pages = {522-535}, doi = {10.1007/s10495-009-0312-3}, pmid = {19156527}, issn = {1573-675X}, mesh = {Animals ; Apoptosis/*immunology ; Caspases/immunology ; Cell Death/immunology ; Humans ; Infections/*immunology ; Inflammation/*immunology ; Models, Immunological ; }, abstract = {Two of the main challenges that multicellular organisms faced during evolution were to cope with invading microorganisms and eliminate and replace dying cells. Our innate immune system evolved to handle both tasks. Key aspects of innate immunity are the detection of invaders or tissue injury and the activation of inflammation that alarms the system through the action of cytokine and chemokine cascades. While inflammation is essential for host resistance to infections, it is detrimental when produced chronically or in excess and is linked to various diseases, most notably auto-immune diseases, auto-inflammatory disorders, cancer and septic shock. Essential regulators of inflammation are enzymes termed "the inflammatory caspases". They are activated by cellular sensors of danger signals, the inflammasomes, and subsequently convert pro-inflammatory cytokines into their mature active forms. In addition, they regulate non-conventional protein secretion of alarmins and cytokines, glycolysis and lipid biogenesis, and the execution of an inflammatory form of cell death termed "pyroptosis". By acting as key regulators of inflammation, energy metabolism and cell death, inflammatory caspases and inflammasomes exert profound influences on innate immunity and infectious and non-infectious inflammatory diseases.}, } @article {pmid19154376, year = {2009}, author = {Willensdorfer, M}, title = {On the evolution of differentiated multicellularity.}, journal = {Evolution; international journal of organic evolution}, volume = {63}, number = {2}, pages = {306-323}, doi = {10.1111/j.1558-5646.2008.00541.x}, pmid = {19154376}, issn = {1558-5646}, support = {R01GM078986/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; *Cell Differentiation ; Eukaryota/cytology ; Fungi/cytology ; *Models, Genetic ; }, abstract = {Most conspicuous organisms are multicellular and most multicellular organisms develop somatic cells to perform specific, nonreproductive tasks. The ubiquity of this division of labor suggests that it is highly advantageous. In this article I present a model to study the evolution of specialized cells. The model allows for unicellular and multicellular organisms that may contain somatic (terminally differentiated) cells. Cells contribute additively to a quantitative trait. The fitness of the organism depends on this quantitative trait (via a benefit function), the size of the organism, and the number of somatic cells. The model allows one to determine when somatic cells are advantageous and to calculate the optimum number (or fraction) of reproductive cells. I show that the fraction of reproductive cells is always surprisingly high. If somatic cells are very small, they can outnumber reproductive cells but their biomass is still less than the biomass of reproductive cells. I discuss the biology of primitive multicellular organisms with respect to the model predictions. I find a good agreement and outline how this work can be used to guide further quantitative studies of multicellularity.}, } @article {pmid19152504, year = {2009}, author = {Mansfield, KD and Keene, JD}, title = {The ribonome: a dominant force in co-ordinating gene expression.}, journal = {Biology of the cell}, volume = {101}, number = {3}, pages = {169-181}, pmid = {19152504}, issn = {1768-322X}, support = {F32 NS059100/NS/NINDS NIH HHS/United States ; CA94365/CA/NCI NIH HHS/United States ; R21 CA094365/CA/NCI NIH HHS/United States ; 5F32NS059100/NS/NINDS NIH HHS/United States ; R33 CA094365/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; RNA/*genetics/*metabolism ; RNA-Binding Proteins/genetics/metabolism ; Ribonucleoproteins/*genetics/*metabolism ; }, abstract = {The ribonome is the total cellular complement of RNAs and their regulatory factors functioning dynamically in time and space within ribonucleoprotein complexes. We theorize that the ribonome is an ancient central co-ordinator that has evolved to communicate on multiple levels to the proteome on the one hand (feed-forward), and the transcriptome and RNA processing machinery on the other (feed-back). Furthermore, the ribonome can potentially communicate to other cells horizontally with implications for biological information transfer and for the evolution of both RNA and DNA operating systems. The post-transcriptional RNA operon theory of co-regulated gene expression accounts for the co-ordinated dynamics of RNA-binding proteins within the cellular ribonome, thus allowing for the recombination and remodelling of the RNPs (ribonucleoproteins) to generate new combinations of functionally related proteins. Thus, post-transcriptional RNA operons form the core of the ribonomic operating system in which both their control and co-ordination govern outcomes. Within the ribonome, RNA-binding proteins control one another's mRNAs to keep the global mRNA environment in balance. We argue that these post-transcriptional ribonomic systems provide an information management and distribution centre for evolutionary expansion of multicellularity in tissues, organs, organisms, and their communities.}, } @article {pmid19150962, year = {2008}, author = {Pearson, BJ and Sánchez Alvarado, A}, title = {Regeneration, stem cells, and the evolution of tumor suppression.}, journal = {Cold Spring Harbor symposia on quantitative biology}, volume = {73}, number = {}, pages = {565-572}, doi = {10.1101/sqb.2008.73.045}, pmid = {19150962}, issn = {1943-4456}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Adult Stem Cells/cytology/physiology ; Animals ; Biological Evolution ; Cell Proliferation ; Drosophila ; Eukaryota ; Genes, Tumor Suppressor ; Humans ; Longevity ; Neoplasms/genetics/pathology/*prevention & control ; Planarians ; Regeneration/genetics/*physiology ; Stem Cells/cytology/*physiology ; Vertebrates ; }, abstract = {All multicellular organisms have requirements for tumor suppression to regulate cellular proliferation during either embryonic development or adult life. However, different organisms have vastly different requirements. Adult tumor suppression is probably not crucial to organisms possessing both short life spans and largely postmitotic soma. In contrast, animals with lifelong tissue turnover or those capable of regenerating body parts lost to injury must possess evolutionarily selected mechanisms to control rates of cell proliferation such that tissue homeostasis can be maintained or restored after injury. We hypothesize that these biological differences may help to explain why the lists of tumor suppressor genes in humans and Drosophila are largely nonoverlapping. Here, we address this disparity by examining the tumor suppressor gene content of two outgroups to the vertebrates and flies/nematodes: the freshwater planarian and the single-celled choanoflagellate. Both of these organisms have recently had their genomes sequenced, giving us a first glimpse of which known tumor suppressor genes have been maintained during evolution. In addition, we attempt to resolve which genes may have had ancestral tumor suppressor function and which may have acquired this function de novo.}, } @article {pmid19146945, year = {2009}, author = {Guo, WJ and Ling, J and Li, P}, title = {Consensus features of microsatellite distribution: microsatellite contents are universally correlated with recombination rates and are preferentially depressed by centromeres in multicellular eukaryotic genomes.}, journal = {Genomics}, volume = {93}, number = {4}, pages = {323-331}, doi = {10.1016/j.ygeno.2008.12.009}, pmid = {19146945}, issn = {1089-8646}, mesh = {Arabidopsis/genetics ; Centromere/*genetics ; Chromosomes/genetics ; Eukaryotic Cells/metabolism ; *Genome ; Humans ; Microsatellite Repeats/*genetics ; Oryza/genetics ; Recombination, Genetic/*genetics ; }, abstract = {Microsatellite DNA is highly polymorphic and informative, which makes its distribution pattern and its associations very valuable for marker applications and genomic research in evolution. Using computational and statistical approaches, based on database technology, we have demonstrated that microsatellite content is consistently and significantly 2 to 5 fold lower than the average chromosomal level in the centromeric and pericentromeric regions of the chromosomes of two plant species, Arabidopsis thaliana and Oryza sativa. We conducted a path coefficient analysis to compare the direct effect of microsatellites (from mono-nucleotide through to penta-nucleotide repeats) on recombination rates. The results revealed that tri- and penta-nucleotide microsatellites significantly influence recombination rates. In the human genome, tri-, tetra- and mono-nucleotide microsatellites, in decreasing order, make significant direct contributions to recombination rates, according to DECODE, GENTHON, and MARSHFIELD averages. Path coefficient analysis in rice and human genomes of the impact of di-nucleotide microsatellites of different motifs on recombination rates indicate that motifs with either A or T have an effect, resulting in increased recombination rates for microsatellites with motifs consisting of 50% A or T, such as AG, TC, CA, TG. Conversely, microsatellites with motifs consisting of only A & T or G & C, such as AT, TA, GC or CG, have decreased recombination rates. The extremely low microsatellite content in centromeric and pericentromeric regions, as well as the quantitative association of microsatellite sequences with the recombination rate at the genome level, suggests that purifying selection in genome evolution creates a balance between genomic polymorphisms and the biological function of sequences in a genome.}, } @article {pmid19141858, year = {2009}, author = {Yang, Y}, title = {Growth and patterning in the limb: signaling gradients make the decision.}, journal = {Science signaling}, volume = {2}, number = {53}, pages = {pe3}, doi = {10.1126/scisignal.253pe3}, pmid = {19141858}, issn = {1937-9145}, mesh = {Animals ; Body Patterning/*physiology ; Cell Division ; Cell Lineage ; Ectoderm/physiology ; Embryonic Development/physiology ; Extremities/*embryology ; Fibroblast Growth Factors/physiology ; Intercellular Signaling Peptides and Proteins/physiology ; Mesoderm/physiology ; Morphogenesis ; Osmolar Concentration ; Signal Transduction/*physiology ; Vertebrates/*embryology ; Wnt Proteins/physiology ; }, abstract = {The vertebrate limb bud provides a unique system to investigate the coordinated regulation of growth and patterning, two key processes that govern the formation of a complex multicellular organism from a fertilized egg. Two studies have advanced our understanding of limb development by elucidating that signaling gradients from the limb ectoderm, including the apical ectoderm ridge (AER), act in concert to establish a basic pattern of tissue layers by coordinating cell proliferation and cell fate determination. These studies reveal that cell proliferation and fate determination in development can be two faces of the same coin in that they are regulated by the same signaling pathways. Alterations in the duration and range of the signaling gradients may underlie many of the morphological differences in the evolution of vertebrate limbs.}, } @article {pmid19140332, year = {2008}, author = {Sliusarev, GS}, title = {[Phylum Orthonectida: morphology, biology, and relationships to other multicellular animals].}, journal = {Zhurnal obshchei biologii}, volume = {69}, number = {6}, pages = {403-427}, pmid = {19140332}, issn = {0044-4596}, mesh = {Animals ; Female ; *Host-Parasite Interactions ; *Invertebrates/anatomy & histology/classification/growth & development ; Male ; Phylogeny ; Reproduction ; }, abstract = {New data on morphology of the ciliary cells, sex pore, cuticle formation, sperm cell, and plasmodium in the Orthonectida were obtained. Interdigitating ciliary cells constitute a single-row epithelial layer underlied by the intercellular matrix but the basal plate formed by the matrix is not solid. Orthonectids are shown to possess the genuine muscle system consisting of the outer circular and inner longitudinal muscles. Metameric arrangement of the circular muscles in Intoshia linei, Rhopalura litoralis, and Rhopalura philinae corresponds to the integument netamery, the circular muscles underlying the circles of non-ciliary cells. In different species the longitudinal muscles form 4 to 6 bilateral cords. The longitudinal muscles provide body bending during pivots of the ciliary locomotion; they are also involved in the copulation as well as in the extrusion of genital pore cells, sperm cells, and larvae. Formation of the muscle cords in the embryogenesis is preceded by the stage of a solid layer of presumptive myoblasts at the boundary between outer and inner cell layers. Multicellular receptor in adult orthonectids is described. Finding both the muscle system and the multicellular receptor evidences for the existence of the nervous system in the orthonectids. A group of cells forming a putative ganglion is revealed in the anterior part of the ciliary individuals. Orthonectid cuticle is of microvillar type resembling that of Annelida. Comparison of reproductive individuals in Orthonectida and Dicyemida indicates that these taxa are distinct phyla belonging to quite separate branches of the Metazoan phylogenetic tree. New data on morphology and biology of the orthonectid plasmodium are obtained. The mechanism of the orthonectid leaving their hosts is described: the reproductive individuals move within the plasmodium processes that grow through the host tissues and contact with the environment. The plasmodium is shown to be covered with two membranes and is proved to contain multiple nuclei. The data obtained evidence for the parasitic nature of the orthonectid plasmodium. The orthonectid life cycle includes alternation of the sexual, asexual, and parthenogenetic reproduction phases and can be characterized as a combination of the metagenesis and heterogony. The term "metaheterogony" is suggested to denotate the orthonectid life cycle. By the entire set of the morphological characters, the orthonectids are to be allocated to the Spiralia.}, } @article {pmid19124078, year = {2009}, author = {Anava, S and Rand, D and Zilberstein, Y and Ayali, A}, title = {Innexin genes and gap junction proteins in the locust frontal ganglion.}, journal = {Insect biochemistry and molecular biology}, volume = {39}, number = {3}, pages = {224-233}, doi = {10.1016/j.ibmb.2008.12.002}, pmid = {19124078}, issn = {1879-0240}, mesh = {Amino Acid Sequence ; Animals ; Cloning, Molecular ; Connexins/chemistry/*genetics/metabolism ; Female ; Ganglia, Invertebrate/chemistry/*metabolism ; Gene Expression ; Grasshoppers/chemistry/classification/*genetics/metabolism ; Insect Proteins/chemistry/*genetics/metabolism ; Male ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Sequence Alignment ; }, abstract = {Gap junctions (GJs) belong to one of the most conserved cellular structures in multicellular organisms. They probably serve similar functions in all Metazoa, providing one of the most common forms of intercellular communication. GJs are widely distributed in embryonic cells and tissues and have been attributed an important role in development, modulating cell growth and differentiation. These channels have been also implicated in mediating electrical synaptic signaling; Coupling through GJs is now accepted as a major pathway that supports network behavior and contributes to physiological rhythms. Here we focus on the physiology and molecular biology of GJs in a recently established model for the study of rhythm-generating networks and their role in behavior: the frontal ganglion (FG) of the desert locust, Schistocerca gregaria. Four novel genes of the invertebrate GJs (innexin) gene family were found to be expressed in the FG: Sg-inx1, Sg-inx2, Sg-inx3 and Sg-inx4. Immunohistochemistry revealed that some of the neurons in the FG express at least one innexin protein, INX1. We also established the presence of functional gap junction proteins in the FG and demonstrated functional electrical coupling between the neurons in the FG. This study forms the basis for further investigation of the role of GJs in network development and behavior.}, } @article {pmid19121120, year = {2009}, author = {Sohani, MM and Schenk, PM and Schultz, CJ and Schmidt, O}, title = {Phylogenetic and transcriptional analysis of a strictosidine synthase-like gene family in Arabidopsis thaliana reveals involvement in plant defence responses.}, journal = {Plant biology (Stuttgart, Germany)}, volume = {11}, number = {1}, pages = {105-117}, doi = {10.1111/j.1438-8677.2008.00139.x}, pmid = {19121120}, issn = {1435-8603}, mesh = {Animals ; Arabidopsis/*genetics/physiology ; Arabidopsis Proteins/classification/*genetics ; Caenorhabditis/genetics ; Carbon-Nitrogen Lyases/*genetics ; Cucumovirus/pathogenicity ; Drosophila/genetics ; Escherichia coli ; Gene Expression ; Gene Expression Regulation, Plant ; *Genes, Plant ; Phylogeny ; Plant Diseases/*genetics ; Plant Growth Regulators/*physiology ; Plant Physiological Phenomena/genetics ; Sequence Analysis, DNA ; Signal Transduction/genetics ; }, abstract = {Protein domains with similarity to plant strictosidine synthase-like (SSL) sequences have been uncovered in the genomes of all multicellular organisms sequenced so far and are known to play a role in animal immune responses. Among several distinct groups of Arabidopsis thaliana SSL sequences, four genes (AtSSL4-AtSSL7) arranged in tandem on chromosome 3 show more similarity to SSL genes from Drosophila melanogaster and Caenorhabditis elegans than to other Arabidopsis SSL genes. To examine whether any of the four AtSSL genes are immune-inducible, we analysed the expression of each of the four AtSSL genes after exposure to microbial pathogens, wounding and plant defence elicitors using real-time quantitative RT-PCR, Northern blot hybridisation and Western blot analysis with antibodies raised against recombinant AtSSL proteins. While the AtSSL4 gene was constitutively expressed and not significantly induced by any treatment, the other three AtSSL genes were induced to various degrees by plant defence signalling compounds, such as salicylic acid, methyl jasmonate and ethylene, as well as by wounding and exposure to the plant pathogens Alternaria brassicicola and cucumber mosaic virus. Our data demonstrate that the four SSL-coding genes are regulated individually, suggesting specific roles in basal (SSL4) and inducible (SSL5-7) plant defence mechanisms.}, } @article {pmid19119411, year = {2009}, author = {Airoldi, EM and Huttenhower, C and Gresham, D and Lu, C and Caudy, AA and Dunham, MJ and Broach, JR and Botstein, D and Troyanskaya, OG}, title = {Predicting cellular growth from gene expression signatures.}, journal = {PLoS computational biology}, volume = {5}, number = {1}, pages = {e1000257}, pmid = {19119411}, issn = {1553-7358}, support = {R01 GM046406/GM/NIGMS NIH HHS/United States ; R37 GM046406/GM/NIGMS NIH HHS/United States ; R01 GM107466/GM/NIGMS NIH HHS/United States ; P50 GM071508/GM/NIGMS NIH HHS/United States ; R01 GM071966/GM/NIGMS NIH HHS/United States ; R01 GM076562/GM/NIGMS NIH HHS/United States ; GM 071508/GM/NIGMS NIH HHS/United States ; GM 46406/GM/NIGMS NIH HHS/United States ; T32 HG003284/HG/NHGRI NIH HHS/United States ; }, mesh = {*Algorithms ; Cell Proliferation ; Computer Simulation ; Gene Expression Profiling/*methods ; *Models, Biological ; Proteome/*metabolism ; Saccharomyces cerevisiae/*growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {Maintaining balanced growth in a changing environment is a fundamental systems-level challenge for cellular physiology, particularly in microorganisms. While the complete set of regulatory and functional pathways supporting growth and cellular proliferation are not yet known, portions of them are well understood. In particular, cellular proliferation is governed by mechanisms that are highly conserved from unicellular to multicellular organisms, and the disruption of these processes in metazoans is a major factor in the development of cancer. In this paper, we develop statistical methodology to identify quantitative aspects of the regulatory mechanisms underlying cellular proliferation in Saccharomyces cerevisiae. We find that the expression levels of a small set of genes can be exploited to predict the instantaneous growth rate of any cellular culture with high accuracy. The predictions obtained in this fashion are robust to changing biological conditions, experimental methods, and technological platforms. The proposed model is also effective in predicting growth rates for the related yeast Saccharomyces bayanus and the highly diverged yeast Schizosaccharomyces pombe, suggesting that the underlying regulatory signature is conserved across a wide range of unicellular evolution. We investigate the biological significance of the gene expression signature that the predictions are based upon from multiple perspectives: by perturbing the regulatory network through the Ras/PKA pathway, observing strong upregulation of growth rate even in the absence of appropriate nutrients, and discovering putative transcription factor binding sites, observing enrichment in growth-correlated genes. More broadly, the proposed methodology enables biological insights about growth at an instantaneous time scale, inaccessible by direct experimental methods. Data and tools enabling others to apply our methods are available at http://function.princeton.edu/growthrate.}, } @article {pmid20943124, year = {2009}, author = {Wimpenny, J}, title = {Microbial metropolis.}, journal = {Advances in microbial physiology}, volume = {56}, number = {}, pages = {29-84}, doi = {10.1016/S0065-2911(09)05602-1}, pmid = {20943124}, issn = {2162-5468}, mesh = {Animals ; Bacterial Adhesion ; Biofilms/*growth & development ; Biological Evolution ; Biomass ; Drug Resistance, Bacterial ; *Ecosystem ; Food Microbiology ; Humans ; Models, Biological ; Quorum Sensing ; }, abstract = {Microorganisms can form tightly knit communities such as biofilms. Many others include marine snow, anaerobic digester granules, the ginger beer plant and bacterial colonies. This chapter is devoted to a survey of the main properties of these communities, with an emphasis on biofilms. We start with attachment to surfaces and the nature of adhesion. The growing community then forms within a matrix, generally of organic macromolecules. Inevitably the environment within such a matrix is different from that outside. Organisms respond by forming crowd-detection and response units; these quorum sensing systems act as switches between planktonic life and the dramatically altered conditions found inside microbial aggregates. The community then matures and changes and may even fail and disappear. Antimicrobial resistance is discussed as an example of multicellular behavior. The multicellular lifestyle has been modeled mathematically and responded to powerful molecular biological techniques. Latterly, microbial systems have been used as models for fundamental evolutionary processes, mostly because of their high rates of reproduction and the ease of genetic manipulation. The life of most microbes is a duality between the yin of the community and the yang of planktonic existence. Sadly far less research has been devoted to adaptation to free-living forms than in the opposite direction.}, } @article {pmid19112042, year = {2009}, author = {Dolan, L}, title = {Body building on land: morphological evolution of land plants.}, journal = {Current opinion in plant biology}, volume = {12}, number = {1}, pages = {4-8}, doi = {10.1016/j.pbi.2008.12.001}, pmid = {19112042}, issn = {1879-0356}, support = {BBS/E/J/0000A218/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Diploidy ; Plant Leaves/anatomy & histology ; Plant Proteins/metabolism ; Plant Roots/anatomy & histology ; Plants/*anatomy & histology ; }, abstract = {Land plants are derived from green algal ancestors and made their first appearance on land 460 million years ago. The life cycle of the land plant body comprises two multicellular stages -- one haploid (gametophyte) and the other diploid (sporophyte). Recent discoveries suggest that the genes controlling diploid development in ancestral green algal zygotes diversified in the land plant lineage where they control the development of the diploid body plan. There are also numerous examples of the independent recruitment of sets of genes to control the development of structures that are morphologically and functionally similar. These discoveries are giving insights into the mechanism by which land plant morphologies changed over the past 460 million years.}, } @article {pmid19106296, year = {2009}, author = {Payne, JL and Boyer, AG and Brown, JH and Finnegan, S and Kowalewski, M and Krause, RA and Lyons, SK and McClain, CR and McShea, DW and Novack-Gottshall, PM and Smith, FA and Stempien, JA and Wang, SC}, title = {Two-phase increase in the maximum size of life over 3.5 billion years reflects biological innovation and environmental opportunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {106}, number = {1}, pages = {24-27}, pmid = {19106296}, issn = {1091-6490}, mesh = {Animals ; Atmosphere ; *Biological Evolution ; *Body Size/genetics ; *Environment ; *Eukaryotic Cells ; Fossils ; History, Ancient ; Oxygen ; }, abstract = {The maximum size of organisms has increased enormously since the initial appearance of life >3.5 billion years ago (Gya), but the pattern and timing of this size increase is poorly known. Consequently, controls underlying the size spectrum of the global biota have been difficult to evaluate. Our period-level compilation of the largest known fossil organisms demonstrates that maximum size increased by 16 orders of magnitude since life first appeared in the fossil record. The great majority of the increase is accounted for by 2 discrete steps of approximately equal magnitude: the first in the middle of the Paleoproterozoic Era (approximately 1.9 Gya) and the second during the late Neoproterozoic and early Paleozoic eras (0.6-0.45 Gya). Each size step required a major innovation in organismal complexity--first the eukaryotic cell and later eukaryotic multicellularity. These size steps coincide with, or slightly postdate, increases in the concentration of atmospheric oxygen, suggesting latent evolutionary potential was realized soon after environmental limitations were removed.}, } @article {pmid19093090, year = {2008}, author = {Wu, H and Zou, D and Gao, K}, title = {Impacts of increased atmospheric CO2 concentration on photosynthesis and growth of micro- and macro-algae.}, journal = {Science in China. Series C, Life sciences}, volume = {51}, number = {12}, pages = {1144-1150}, doi = {10.1007/s11427-008-0142-5}, pmid = {19093090}, issn = {1006-9305}, mesh = {Atmosphere/*chemistry ; Carbon Dioxide/*metabolism ; Environment ; Eukaryota/*physiology ; Oceans and Seas ; Photosynthesis/*physiology ; Phytoplankton/physiology ; Seawater ; }, abstract = {Marine photosynthesis drives the oceanic biological CO(2) pump to absorb CO(2) from the atmosphere, which sinks more than one third of the industry-originated CO(2) into the ocean. The increasing atmospheric CO(2) and subsequent rise of pCO(2) in seawater, which alters the carbonate system and related chemical reactions and results in lower pH and higher HCO(3) (-) concentration, affect photosynthetic CO(2) fixation processes of phytoplanktonic and macroalgal species in direct and/or indirect ways. Although many unicellular and multicellular species can operate CO(2)-concentrating mechanisms (CCMs) to utilize the large HCO(3) (-) pool in seawater, enriched CO(2) up to several times the present atmospheric level has been shown to enhance photosynthesis and growth of both phytoplanktonic and macro-species that have less capacity of CCMs. Even for species that operate active CCMs and those whose photosynthesis is not limited by CO(2) in seawater, increased CO(2) levels can down-regulate their CCMs and therefore enhance their growth under light-limiting conditions (at higher CO(2) levels, less light energy is required to drive CCM). Altered physiological performances under high-CO(2) conditions may cause genetic alteration in view of adaptation over long time scale. Marine algae may adapt to a high CO(2) oceanic environment so that the evolved communities in future are likely to be genetically different from the contemporary communities. However, most of the previous studies have been carried out under indoor conditions without considering the acidifying effects on seawater by increased CO(2) and other interacting environmental factors, and little has been documented so far to explain how physiology of marine primary producers performs in a high-CO(2) and low-pH ocean.}, } @article {pmid19079286, year = {2009}, author = {Kourtis, N and Tavernarakis, N}, title = {Autophagy and cell death in model organisms.}, journal = {Cell death and differentiation}, volume = {16}, number = {1}, pages = {21-30}, doi = {10.1038/cdd.2008.120}, pmid = {19079286}, issn = {1476-5403}, mesh = {Animals ; Autophagy/*physiology ; Caenorhabditis elegans/physiology ; Cell Survival/physiology ; Dictyostelium/physiology ; Drosophila melanogaster ; Humans ; *Models, Biological ; Saccharomyces cerevisiae/physiology ; Signal Transduction/physiology ; Stress, Physiological/*physiology ; }, abstract = {Autophagy evolved in unicellular eukaryotes as a means for surviving nutrient stress. During the course of evolution, as multicellular organisms developed specialized cell types and complex intracellular signalling networks, autophagy has been summoned to serve additional cellular functions. Numerous recent studies indicate that apart from its pro-survival role under nutrient limitation, autophagy also participates in cell death. However, the precise role of this catabolic process in dying cells is not fully understood. Although in certain situations autophagy has a protective function, in other types of cell death it actually contributes to cellular destruction. Simple model organisms ranging from the unicellular Saccharomyces cerevisiae to the soil amoeba Dictyostelium discoideum and the metazoans Caenorhabditis elegans and Drosophila melanogaster provide clearly defined cell death paradigms that can be used to dissect the involvement of autophagy in cell death, at the molecular level. In this review, we survey current research in simple organisms, linking autophagy to cell death and discuss the complex interplay between autophagy, cell survival and cell death.}, } @article {pmid19078958, year = {2009}, author = {Lavik, G and Stührmann, T and Brüchert, V and Van der Plas, A and Mohrholz, V and Lam, P and Mussmann, M and Fuchs, BM and Amann, R and Lass, U and Kuypers, MM}, title = {Detoxification of sulphidic African shelf waters by blooming chemolithotrophs.}, journal = {Nature}, volume = {457}, number = {7229}, pages = {581-584}, pmid = {19078958}, issn = {1476-4687}, mesh = {Biodegradation, Environmental ; *Eutrophication ; Hydrogen Sulfide/*metabolism ; Molecular Sequence Data ; Namibia ; Oceans and Seas ; Oxidation-Reduction ; Phylogeny ; Proteobacteria/genetics/*growth & development/isolation & purification/*metabolism ; RNA, Ribosomal, 16S/genetics ; Seawater/*chemistry ; Sulfates/metabolism ; Sulfur/metabolism ; }, abstract = {Coastal waters support approximately 90 per cent of global fisheries and are therefore an important food reserve for our planet. Eutrophication of these waters, due to human activity, leads to severe oxygen depletion and the episodic occurrence of hydrogen sulphide-toxic to multi-cellular life-with disastrous consequences for coastal ecosytems. Here we show that an area of approximately 7,000 km(2) of African shelf, covered by sulphidic water, was detoxified by blooming bacteria that oxidized the biologically harmful sulphide to environmentally harmless colloidal sulphur and sulphate. Combined chemical analyses, stoichiometric modelling, isotopic incubations, comparative 16S ribosomal RNA, functional gene sequence analyses and fluorescence in situ hybridization indicate that the detoxification proceeded by chemolithotrophic oxidation of sulphide with nitrate and was mainly catalysed by two discrete populations of gamma- and epsilon-proteobacteria. Chemolithotrophic bacteria, accounting for approximately 20 per cent of the bacterioplankton in sulphidic waters, created a buffer zone between the toxic sulphidic subsurface waters and the oxic surface waters, where fish and other nekton live. This is the first time that large-scale detoxification of sulphidic waters by chemolithotrophs has been observed in an open-ocean system. The data suggest that sulphide can be completely consumed by bacteria in the subsurface waters and, thus, can be overlooked by remote sensing or monitoring of shallow coastal waters. Consequently, sulphidic bottom waters on continental shelves may be more common than previously believed, and could therefore have an important but as yet neglected effect on benthic communities.}, } @article {pmid19067957, year = {2008}, author = {Bonente, G and Passarini, F and Cazzaniga, S and Mancone, C and Buia, MC and Tripodi, M and Bassi, R and Caffarri, S}, title = {The occurrence of the psbS gene product in Chlamydomonas reinhardtii and in other photosynthetic organisms and its correlation with energy quenching.}, journal = {Photochemistry and photobiology}, volume = {84}, number = {6}, pages = {1359-1370}, doi = {10.1111/j.1751-1097.2008.00456.x}, pmid = {19067957}, issn = {0031-8655}, mesh = {Amino Acid Sequence ; Animals ; Antibodies/immunology ; Chlamydomonas reinhardtii/enzymology/*genetics/immunology/*metabolism ; Color ; Cross Reactions/immunology ; *Energy Transfer ; Epitopes/immunology ; Gene Expression Regulation, Enzymologic ; Molecular Sequence Data ; Mutation/genetics ; Phenotype ; *Photosynthesis ; Photosystem II Protein Complex/chemistry/genetics/immunology/*metabolism ; Phylogeny ; Recombinant Proteins/genetics/immunology/metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {To avoid photodamage, photosynthetic organisms have developed mechanisms to evade or dissipate excess energy. Lumen overacidification caused by light-induced electron transport triggers quenching of excited chlorophylls and dissipation of excess energy into heat. In higher plants participation of the PsbS protein as the sensor of low lumenal pH was clearly demonstrated. Although light-dependent energy quenching is a property of all photosynthetic organisms, large differences in amplitude and kinetics can be observed thus raising the question whether a single common mechanism is in action. We performed a detailed study of PsbS expression/accumulation in Chlamydomonas reinhardtii and investigated its accumulation in other algae and plants. We showed that PsbS cannot be detected in Chlamydomonas under a wide range of growth conditions. Overexpression of the endogenous psbs gene showed that the corresponding protein could not be addressed to the thylakoid membranes. Survey of different unicellular green algae showed no accumulation of anti-PsbS reactive proteins differently from multicellular species. Nevertheless, some unicellular species exhibit high energy quenching activity, suggesting that a PsbS-independent mechanism is activated. By correlating growth habitat and PsbS accumulation in different species, we suggest that during the evolution the light environment has been a determinant factor for the conservation/loss of the PsbS function.}, } @article {pmid19067751, year = {2009}, author = {Nadell, CD and Xavier, JB and Foster, KR}, title = {The sociobiology of biofilms.}, journal = {FEMS microbiology reviews}, volume = {33}, number = {1}, pages = {206-224}, doi = {10.1111/j.1574-6976.2008.00150.x}, pmid = {19067751}, issn = {0168-6445}, support = {5P50 GM 068763-01/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/chemistry/genetics/metabolism ; *Bacterial Physiological Phenomena ; Biofilms/*growth & development ; Biological Evolution ; Models, Biological ; }, abstract = {Biofilms are densely packed communities of microbial cells that grow on surfaces and surround themselves with secreted polymers. Many bacterial species form biofilms, and their study has revealed them to be complex and diverse. The structural and physiological complexity of biofilms has led to the idea that they are coordinated and cooperative groups, analogous to multicellular organisms. We evaluate this idea by addressing the findings of microbiologists from the perspective of sociobiology, including theories of collective behavior (self-organization) and social evolution. This yields two main conclusions. First, the appearance of organization in biofilms can emerge without active coordination. That is, biofilm properties such as phenotypic differentiation, species stratification and channel formation do not necessarily require that cells communicate with one another using specialized signaling molecules. Second, while local cooperation among bacteria may often occur, the evolution of cooperation among all cells is unlikely for most biofilms. Strong conflict can arise among multiple species and strains in a biofilm, and spontaneous mutation can generate conflict even within biofilms initiated by genetically identical cells. Biofilms will typically result from a balance between competition and cooperation, and we argue that understanding this balance is central to building a complete and predictive model of biofilm formation.}, } @article {pmid19066034, year = {2008}, author = {Wagoner, MP and Ling, K and Anderson, RA}, title = {Tracking the transport of E-cadherin to and from the plasma membrane.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {457}, number = {}, pages = {267-278}, pmid = {19066034}, issn = {1064-3745}, support = {R01 CA104708/CA/NCI NIH HHS/United States ; R01 CA104708-03/CA/NCI NIH HHS/United States ; R01 GM057549/GM/NIGMS NIH HHS/United States ; R01 GM114386/GM/NIGMS NIH HHS/United States ; R01 GM057549-08/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Assay ; Biotin/metabolism ; Blotting, Western ; Cadherins/*metabolism ; Cell Line ; Cell Membrane/*metabolism ; Dogs ; Endocytosis ; Fluorescent Antibody Technique ; Molecular Biology/*methods ; Phosphotransferases (Alcohol Group Acceptor)/deficiency/metabolism ; Protein Transport ; Staining and Labeling ; }, abstract = {The epithelial to mesenchymal transition (EMT) is the breakdown of epithelial cell morphology that gives way to a more mobile, mesenchymal phenotype. Although this process is fundamental to the development of multicellular organisms, it is also a key occurrence in many diseases, including cancers of epithelial origin E-cadherin is a central component of adherens junctions (AJs), which act as structural and signaling hubs in epithelial cells that oppose EMT. The loss of E-cadherin from the plasma membrane is an early indication of EMT and a marker of poor prognosis in many cancers making the trafficking of E-cadherin an area of great interest. Recent work from the authors' laboratory has established the role of type I gamma phosphatidylinositol 4-phosphate 5-kinase (PIPKI gamma) in the trafficking of E-cadherin by studying the surface accessibility of E-cadherin in endocytosis and recycling assays. Additionally, immunofluorescence data demonstrated that cells lacking PIPKI gamma lost E-cadherin at the plasma membrane. The biochemical and microscopic techniques used to investigate the trafficking of E-cadherin are presented herein.}, } @article {pmid19063683, year = {2009}, author = {Ryser, MD and Nigam, N and Komarova, SV}, title = {Mathematical modeling of spatio-temporal dynamics of a single bone multicellular unit.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {24}, number = {5}, pages = {860-870}, doi = {10.1359/jbmr.081229}, pmid = {19063683}, issn = {1523-4681}, mesh = {Bone and Bones/*physiology ; Computer Simulation ; Fractures, Bone/pathology ; *Models, Biological ; Osteoblasts/metabolism ; Osteoprotegerin/metabolism ; RANK Ligand/metabolism ; Solubility ; Time Factors ; }, abstract = {During bone remodeling, bone-resorbing osteoclasts and bone-forming osteoblasts are organized in bone multicellular units (BMUs), which travel at a rate of 20-40 mum/d for 6-12 mo, maintaining a cylindrical structure. However, the interplay of local BMU geometry with biochemical regulation is poorly understood. We developed a mathematical model of BMU describing changes in time and space of the concentrations of proresorptive cytokine RANKL and its inhibitor osteoprotegerin (OPG), in osteoclast and osteoblast numbers, and in bone mass. We assumed that osteocytes surrounding a microfracture produce RANKL, which attracted osteoclasts. OPG and RANKL were produced by osteoblasts and diffused through bone, RANKL was eliminated by binding to OPG and RANK. Osteoblasts were coupled to osteoclasts through paracrine factors. The evolution of the BMU arising from this model was studied using numerical simulations. Our model recapitulated the spatio-temporal dynamics observed in vivo in a cross-section of bone. In response to a RANKL field, osteoclasts moved as a well-confined cutting cone. The coupling of osteoclasts to osteoblasts allowed for sufficient recruitment of osteoblasts to the resorbed surfaces. The RANKL field was the highest at the microfracture in front of the BMU, whereas the OPG field peaked at the back of the BMU, resulting in the formation of a RANKL/OPG gradient, which strongly affected the rate of BMU progression and its size. Thus, the spatial organization of a BMU provides important constraints on the roles of RANKL and OPG as well as possibly other regulators in determining the outcome of remodeling in the BMU.}, } @article {pmid19049814, year = {2009}, author = {Babin, PJ and Gibbons, GF}, title = {The evolution of plasma cholesterol: direct utility or a "spandrel" of hepatic lipid metabolism?.}, journal = {Progress in lipid research}, volume = {48}, number = {2}, pages = {73-91}, doi = {10.1016/j.plipres.2008.11.002}, pmid = {19049814}, issn = {1873-2194}, mesh = {Adipose Tissue/metabolism ; Animals ; Biological Evolution ; Cholesterol/*blood ; Cholesterol, LDL/physiology ; Cholesterol, VLDL/physiology ; Fatty Acids/metabolism ; Humans ; Lipid Metabolism/genetics/*physiology ; Liver/*metabolism ; Models, Animal ; Selection, Genetic ; }, abstract = {Fats provide a concentrated source of energy for multicellular organisms. The efficient transport of fats through aqueous biological environments raises issues concerning effective delivery to target tissues. Furthermore, the utilization of fatty acids presents a high risk of cytotoxicity. Improving the efficiency of fat transport while simultaneously minimizing the cytotoxic risk confers distinct selective advantages. In humans, most of the plasma cholesterol is associated with low-density lipoprotein (LDL), a metabolic by-product of very-low-density lipoprotein (VLDL), which originates in the liver. However, the functions of VLDL are not clear. This paper reviews the evidence that LDL arose as a by-product during the natural selection of VLDL. The latter, in turn, evolved as a means of improving the efficiency of diet-derived fatty acid storage and utilization, as well as neutralizing the potential cytotoxicity of fatty acids while conserving their advantages as a concentrated energy source. The evolutionary biology of lipid transport processes has provided a fascinating insight into how and why these VLDL functions emerged during animal evolution. As causes of historical origin must be separated from current utilities, our spandrel-LDL theory proposes that LDL is a spandrel of VLDL selection, which appeared non-adaptively and may later have become crucial for vertebrate fitness.}, } @article {pmid19028579, year = {2009}, author = {Masuya, H and Kusunoki, M and Kosaka, H and Aikawa, T}, title = {Haradamyces foliicola anam. gen. et sp. nov., a cause of zonate leaf blight disease in Cornus florida in Japan.}, journal = {Mycological research}, volume = {113}, number = {Pt 2}, pages = {173-181}, doi = {10.1016/j.mycres.2008.10.004}, pmid = {19028579}, issn = {0953-7562}, mesh = {Ascomycota/classification/*genetics/growth & development ; Cornus/*microbiology ; DNA, Fungal/genetics ; DNA, Ribosomal/genetics ; Japan ; Phylogeny ; Plant Diseases/*microbiology ; Plant Leaves/microbiology ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {A fungus causing zonate leaf blight diseases in various evergreen and deciduous woody plant species in Japan was characterized by a discoid multicellular propagule arising from a hyaline sclerotium-like structure in the leaf tissue and dark-coloured microconidia produced enteroblastically from the terminal cells on the surface of the discoid propagules. Myrioconium-like microconidiophores also producing microconidia were occasionally produced in culture. No teleomorphic characteristics were observed on the fungus. Molecular analysis based on the partial nu-rDNA sequence data revealed that the fungus was phylogenetically related to the Sclerotiniaceae, Leotiomycetes, and Ascomycota. Because the morphology and sequence data of this fungus does not coincide with those of any known anamorphic fungi, Haradamyces foliicola is proposed here as a new anamorphic genus and species for this fungus.}, } @article {pmid19026540, year = {2008}, author = {Matz, MV and Frank, TM and Marshall, NJ and Widder, EA and Johnsen, S}, title = {Giant deep-sea protist produces bilaterian-like traces.}, journal = {Current biology : CB}, volume = {18}, number = {23}, pages = {1849-1854}, doi = {10.1016/j.cub.2008.10.028}, pmid = {19026540}, issn = {1879-0445}, mesh = {Amoeba/classification/genetics/*physiology/ultrastructure ; Animals ; Biological Evolution ; Cnidaria/physiology ; DNA, Protozoan/analysis ; Eukaryota/classification/genetics/*physiology/ultrastructure ; Fossils ; Geologic Sediments/parasitology ; Paleontology ; Phylogeny ; RNA, Ribosomal/genetics ; Seawater/parasitology ; Sequence Analysis, DNA ; }, abstract = {One of the strongest paleontological arguments in favor of the origin of bilaterally symmetrical animals (Bilateria) prior to their obvious and explosive appearance in the fossil record in the early Cambrian, 542 million years ago, is the occurrence of trace fossils shaped like elongated sinuous grooves or furrows in the Precambrian. Being restricted to the seafloor surface, these traces are relatively rare and of limited diversity, and they do not show any evidence of the use of hard appendages. They are commonly attributed to the activity of the early nonskeletonized bilaterians or, alternatively, large cnidarians such as sea anemones or sea pens. Here we describe macroscopic groove-like traces produced by a living giant protist and show that these traces bear a remarkable resemblance to the Precambrian trace fossils, including those as old as 1.8 billion years. This is the first evidence that organisms other than multicellular animals can produce such traces, and it prompts re-evaluation of the significance of Precambrian trace fossils as evidence of the early diversification of Bilateria. Our observations also render indirect support to the highly controversial interpretation of the enigmatic Ediacaran biota of the late Precambrian as giant protists.}, } @article {pmid19016883, year = {2009}, author = {Michalodimitrakis, K and Isalan, M}, title = {Engineering prokaryotic gene circuits.}, journal = {FEMS microbiology reviews}, volume = {33}, number = {1}, pages = {27-37}, pmid = {19016883}, issn = {0168-6445}, support = {201249/ERC_/European Research Council/International ; }, mesh = {Bacteria/*genetics/metabolism ; Directed Molecular Evolution ; Fungi/*genetics/metabolism ; Gene Expression Regulation ; *Gene Regulatory Networks ; Genes, Synthetic ; *Genetic Engineering ; Transcription, Genetic ; }, abstract = {Engineering of synthetic gene circuits is a rapidly growing discipline, currently dominated by prokaryotic transcription networks, which can be easily rearranged or rewired to give different output behaviours. In this review, we examine both a rational and a combinatorial design of such networks and discuss progress on using in vitro evolution techniques to obtain functional systems. Moving beyond pure transcription networks, more and more networks are being implemented at the level of RNA, taking advantage of mechanisms of translational control and aptamer-small molecule complex formation. Unlike gene expression systems, metabolic components are generally not as interconnectable in any combination, and so engineering of metabolic circuits is a particularly challenging field. Nonetheless, metabolic engineering has immense potential to provide useful biosynthesis tools for biotechnology applications. Finally, although prokaryotes are mostly studied as single cell systems, cell-cell communication networks are now being developed that result in spatial pattern formation in multicellular prokaryote colonies. This represents a crossover with multicellular organisms, showing that prokaryotic systems have the potential to tackle questions traditionally associated with developmental biology. Overall, the current advances in synthetic gene synthesis, ultra-high-throughput DNA sequencing and computation are synergizing to drive synthetic gene network design at an unprecedented pace.}, } @article {pmid19014443, year = {2008}, author = {Skinner, A and Lee, MS and Hutchinson, MN}, title = {Rapid and repeated limb loss in a clade of scincid lizards.}, journal = {BMC evolutionary biology}, volume = {8}, number = {}, pages = {310}, pmid = {19014443}, issn = {1471-2148}, mesh = {Animals ; Bayes Theorem ; *Biological Evolution ; Body Patterning ; DNA, Mitochondrial/genetics ; Extremities/*anatomy & histology ; Genes, Mitochondrial ; Genetic Speciation ; Introns ; Likelihood Functions ; Lizards/*anatomy & histology/genetics ; Phylogeny ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: The Australian scincid clade Lerista provides perhaps the best available model for studying limb reduction in squamates (lizards and snakes), comprising more than 75 species displaying a remarkable variety of digit configurations, from pentadactyl to entirely limbless conditions. We investigated the pattern and rate of limb reduction and loss in Lerista, employing a comprehensive phylogeny inferred from nucleotide sequences for a nuclear intron and six mitochondrial genes.

RESULTS: The inferred phylogeny reveals extraordinary evolutionary mutability of limb morphology in Lerista. Ancestral state reconstructions indicate at least ten independent reductions in the number of digits from a pentadactyl condition, with a further seven reductions proceeding independently from a tetradactyl condition derived from one of these reductions. Four independent losses of all digits are inferred, three from pentadactyl or tetradactyl conditions. These conclusions are not substantially affected by uncertainty in assumed rates of character state transition or the phylogeny. An estimated age of 13.4 million years for Lerista entails that limb reduction has occurred not only repeatedly, but also very rapidly. At the highest rate, complete loss of digits from a pentadactyl condition is estimated to have occurred within 3.6 million years.

CONCLUSION: The exceptionally high frequency and rate of limb reduction inferred for Lerista emphasise the potential for rapid and substantial alteration of body form in squamates. An absence of compelling evidence for reversals of digit loss contrasts with a recent proposal that digits have been regained in some species of the gymnophthalmid clade Bachia, possibly reflecting an influence of differing environmental and genetic contexts on the evolution of limb morphology in these clades. Future study of the genetic, developmental, and ecological bases of limb reduction and loss in Lerista promises the elucidation of not only this phenomenon in squamates, but also the dramatic evolutionary transformations of body form that have produced the extraordinary diversity of multicellular organisms.}, } @article {pmid19013190, year = {2009}, author = {Bosch, TC and Augustin, R and Anton-Erxleben, F and Fraune, S and Hemmrich, G and Zill, H and Rosenstiel, P and Jacobs, G and Schreiber, S and Leippe, M and Stanisak, M and Grötzinger, J and Jung, S and Podschun, R and Bartels, J and Harder, J and Schröder, JM}, title = {Uncovering the evolutionary history of innate immunity: the simple metazoan Hydra uses epithelial cells for host defence.}, journal = {Developmental and comparative immunology}, volume = {33}, number = {4}, pages = {559-569}, doi = {10.1016/j.dci.2008.10.004}, pmid = {19013190}, issn = {1879-0089}, mesh = {Amino Acid Sequence ; Animals ; Antimicrobial Cationic Peptides/*genetics/immunology ; Antioxidants/pharmacology ; Base Sequence ; Epithelial Cells/*immunology/microbiology/ultrastructure ; Evolution, Molecular ; Flagellin/immunology ; Gene Expression/drug effects/immunology ; Hydra/*immunology/microbiology/ultrastructure ; *Immunity, Innate ; Microscopy, Electron, Transmission ; Molecular Sequence Data ; Pseudomonas aeruginosa ; Receptors, Cell Surface/drug effects/immunology/metabolism ; Sequence Alignment ; Up-Regulation/drug effects/immunology ; Uric Acid/pharmacology ; }, abstract = {Although many properties of the innate immune system are shared among multicellular animals, the evolutionary origin remains poorly understood. Here we characterize the innate immune system in Hydra, one of the simplest multicellular animals known. In the complete absence of both protective mechanical barriers and mobile phagocytes, Hydra's epithelium is remarkably well equipped with potent antimicrobial peptides to prevent pathogen infection. Induction of antimicrobial peptide production is mediated by the interaction of a leucine-rich repeats (LRRs) domain containing protein with a TIR-domain containing protein lacking LRRs. Conventional Toll-like receptors (TLRs) are absent in the Hydra genome. Our findings support the hypothesis that the epithelium represents the ancient system of host defence.}, } @article {pmid18992809, year = {2009}, author = {Espinosa-Urgel, M}, title = {Multicellularity, neoplasias and biofilms.}, journal = {Research in microbiology}, volume = {160}, number = {1}, pages = {85-86}, doi = {10.1016/j.resmic.2008.09.009}, pmid = {18992809}, issn = {0923-2508}, mesh = {Bacteria/*growth & development ; Biofilms/*growth & development ; Biological Evolution ; Neoplasms/*metabolism ; }, } @article {pmid18987999, year = {2009}, author = {Fujimori, KE}, title = {Characterization of the regulatory region of the dopa decarboxylase gene in Medaka: an in vivo green fluorescent protein reporter assay combined with a simple TA-cloning method.}, journal = {Molecular biotechnology}, volume = {41}, number = {3}, pages = {224-235}, pmid = {18987999}, issn = {1073-6085}, mesh = {Amino Acid Sequence ; Animals ; Chickens ; Cloning, Molecular ; Databases, Genetic ; Dopa Decarboxylase/chemistry/*genetics/metabolism ; Embryo, Nonmammalian/metabolism ; Fish Proteins/chemistry/*genetics/metabolism ; Gene Expression Regulation ; Green Fluorescent Proteins/genetics/metabolism ; Humans ; Mice ; Molecular Sequence Data ; Oryzias/embryology/*genetics/growth & development/metabolism ; Phylogeny ; *Promoter Regions, Genetic ; Sequence Alignment ; Zebrafish ; }, abstract = {The mechanism by which differentiated cells cooperatively express specific sets of genes in multicellular organisms is a fundamental question for biologists. Currently, the mechanism is primarily attributed to complex regulation of transcriptional machinery. Here, I provide a method for studying spatiotemporal characteristics of promoters in vivo by rapid construction of reporter gene-expression vectors based on simple TA-cloning using an in vivo eGFP reporter assay in Medaka (Oryzias latipes). As an application of this method, I focused on the dopa decarboxylase (Ddc) gene, an essential enzyme for production of neurotransmitters, dopamine, and serotonin. Based on the known structure of the Medaka genome, I predicted and cloned the approximately 3 kbp fragment flanking the Ddc gene. Using an eGFP reporter assay in vivo, I showed that it functions as a promoter, directing reporter gene expression in the brain, retina, epiphysis, and gut, but not in sympathetic ganglia, kidney, or liver. Thus, the procedure presented here provides a useful tool for rapid screening of possible promoter regions and for establishing germ line-transmitted transgenic lines of Medaka.}, } @article {pmid18986826, year = {2008}, author = {Swaminathan, K and Peterson, K and Jack, T}, title = {The plant B3 superfamily.}, journal = {Trends in plant science}, volume = {13}, number = {12}, pages = {647-655}, doi = {10.1016/j.tplants.2008.09.006}, pmid = {18986826}, issn = {1360-1385}, mesh = {Amino Acid Sequence ; Arabidopsis/chemistry/*genetics ; Arabidopsis Proteins/chemistry/*genetics ; *Biological Evolution ; Molecular Sequence Data ; Multigene Family ; Oryza/chemistry/*genetics ; Protein Structure, Tertiary ; }, abstract = {The plant-specific B3 superfamily encompasses well-characterized families, such as the auxin response factor (ARF) family and the LAV family, as well as less well understood families, such as RAV and REM. In Arabidopsis, there are 118 B3 genes, and in rice there are 91 B3 genes. The B3 domain is present in genes from gymnosperms, mosses and green algae, indicating that the B3 domain evolved on the plant lineage before multicellularity. The aim of this review is to phylogenetically characterize the members of the B3 family in Arabidopsis and rice and to review the function of the B3 genes that have been studied to date.}, } @article {pmid18983257, year = {2008}, author = {Rokas, A}, title = {The origins of multicellularity and the early history of the genetic toolkit for animal development.}, journal = {Annual review of genetics}, volume = {42}, number = {}, pages = {235-251}, doi = {10.1146/annurev.genet.42.110807.091513}, pmid = {18983257}, issn = {0066-4197}, mesh = {Animals ; Bacteria/cytology/genetics ; Bacterial Physiological Phenomena ; *Biological Evolution ; Cell Adhesion/*genetics ; Cell Communication/*genetics ; Cell Differentiation/genetics ; Eukaryota/cytology/genetics/physiology ; Eukaryotic Cells ; Phylogeny ; Transcription, Genetic ; }, abstract = {Multicellularity appeared early and repeatedly in life's history; its instantiations presumably required the confluence of environmental, ecological, and genetic factors. Comparisons of several independently evolved pairs of multicellular and unicellular relatives indicate that transitions to multicellularity are typically associated with increases in the numbers of genes involved in cell differentiation, cell-cell communication, and adhesion. Further examination of the DNA record suggests that these increases in gene complexity are the product of evolutionary innovation, tinkering, and expansion of genetic material. Arguably, the most decisive multicellular transition was the emergence of animals. Decades of developmental work have demarcated the genetic toolkit for animal multicellularity, a select set of a few hundred genes from a few dozen gene families involved in adhesion, communication, and differentiation. Examination of the DNA records of the earliest-branching animal phyla and their closest protist relatives has begun to shed light on the origins and assembly of this toolkit. Emerging data favor a model of gradual assembly, with components originating and diversifying at different time points prior to or shortly after the origin of animals.}, } @article {pmid18952864, year = {2008}, author = {Porsby, CH and Nielsen, KF and Gram, L}, title = {Phaeobacter and Ruegeria species of the Roseobacter clade colonize separate niches in a Danish Turbot (Scophthalmus maximus)-rearing farm and antagonize Vibrio anguillarum under different growth conditions.}, journal = {Applied and environmental microbiology}, volume = {74}, number = {23}, pages = {7356-7364}, pmid = {18952864}, issn = {1098-5336}, mesh = {Animals ; *Antibiosis ; Bacterial Proteins ; DNA Gyrase/genetics ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Denmark ; Fish Diseases/microbiology/*prevention & control ; Flatfishes/*microbiology ; Genes, rRNA ; Larva/microbiology ; Molecular Sequence Data ; Phylogeny ; Pigments, Biological/biosynthesis ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/*isolation & purification/physiology ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; Tropolone/analogs & derivatives/metabolism ; Vibrio/*growth & development ; Vibrio Infections/prevention & control/*veterinary ; }, abstract = {Members of the Roseobacter clade colonize a Spanish turbot larval unit, and one isolate (Phaeobacter strain 27-4) is capable of disease suppression in in vivo challenge trials. Here, we demonstrate that roseobacters with antagonistic activity against Vibrio anguillarum also colonize a Danish turbot larval farm that relies on a very different water source (the Danish fiord Limfjorden as opposed to the Galician Atlantic Ocean). Phylogenetic analyses based on 16S rRNA and gyrase B gene sequences revealed that different species colonized different niches in the larval unit. Phaeobacter inhibens- and Phaeobacter gallaeciensis-like strains were primarily found in the production sites, whereas strains identified as Ruegeria mobilis or Ruegeria pelagia were found only in the algal cultures. Phaeobacter spp. were more inhibitory against the general microbiota from the Danish turbot larval unit than were the Ruegeria spp. Phaeobacter spp. produced tropodithietic acid (TDA) and brown pigment and antagonized V. anguillarum when grown under shaking (200 rpm) and stagnant (0 rpm) conditions, whereas Ruegeria spp. behaved similarly to Phaeobacter strain 27-4 and expressed these three phenotypes only during stagnant growth. Both genera attached to an inert surface and grew in multicellular rosettes after stagnant growth, whereas shaking conditions led to single cells with low attachment capacity. Bacteria from the Roseobacter clade appear to be universal colonizers of marine larval rearing units, and since the Danish Phaeobacter spp. displayed antibacterial activity under a broader range of growth conditions than did Phaeobacter strain 27-4, these organisms may hold greater promise as fish probiotic organisms.}, } @article {pmid18952316, year = {2009}, author = {Xiao, S and Laflamme, M}, title = {On the eve of animal radiation: phylogeny, ecology and evolution of the Ediacara biota.}, journal = {Trends in ecology & evolution}, volume = {24}, number = {1}, pages = {31-40}, doi = {10.1016/j.tree.2008.07.015}, pmid = {18952316}, issn = {0169-5347}, mesh = {Animals ; Biodiversity ; Ecology ; *Fossils ; *Genetic Speciation ; Phylogeny ; }, abstract = {Ediacara fossils document an important evolutionary episode just before the Cambrian explosion and hold critical information about the early evolution of macroscopic and complex multicellular life. They also represent an enduring controversy in paleontology. How are the Ediacara fossils related to living animals? How did they live? Do they share any evolutionary patterns with other life forms? Recent developments indicate that Ediacara fossils epitomize a phylogenetically diverse biosphere, probably including animals, protists, algae, fungi and others. Their simple ecology is dominated by epibenthic osmotrophs, deposit feeders and grazers, but few if any predators. Their evolution started with an early morphospace expansion followed by taxonomic diversification within confined morphospace, and concluded by extinction of many taxa at the Ediacaran-Cambrian boundary.}, } @article {pmid18949026, year = {2008}, author = {Borenstein, E and Krakauer, DC}, title = {An end to endless forms: epistasis, phenotype distribution bias, and nonuniform evolution.}, journal = {PLoS computational biology}, volume = {4}, number = {10}, pages = {e1000202}, pmid = {18949026}, issn = {1553-7358}, support = {R01 GM028016/GM/NIGMS NIH HHS/United States ; GM28016/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anthropology, Physical ; *Biological Evolution ; *Epistasis, Genetic/physiology ; Gene Regulatory Networks ; Genotype ; Growth and Development/*genetics ; Humans ; *Models, Genetic ; Mutation/physiology ; *Phenotype ; Physiology, Comparative ; }, abstract = {Studies of the evolution of development characterize the way in which gene regulatory dynamics during ontogeny constructs and channels phenotypic variation. These studies have identified a number of evolutionary regularities: (1) phenotypes occupy only a small subspace of possible phenotypes, (2) the influence of mutation is not uniform and is often canalized, and (3) a great deal of morphological variation evolved early in the history of multicellular life. An important implication of these studies is that diversity is largely the outcome of the evolution of gene regulation rather than the emergence of new, structural genes. Using a simple model that considers a generic property of developmental maps-the interaction between multiple genetic elements and the nonlinearity of gene interaction in shaping phenotypic traits-we are able to recover many of these empirical regularities. We show that visible phenotypes represent only a small fraction of possibilities. Epistasis ensures that phenotypes are highly clustered in morphospace and that the most frequent phenotypes are the most similar. We perform phylogenetic analyses on an evolving, developmental model and find that species become more alike through time, whereas higher-level grades have a tendency to diverge. Ancestral phenotypes, produced by early developmental programs with a low level of gene interaction, are found to span a significantly greater volume of the total phenotypic space than derived taxa. We suggest that early and late evolution have a different character that we classify into micro- and macroevolutionary configurations. These findings complement the view of development as a key component in the production of endless forms and highlight the crucial role of development in constraining biotic diversity and evolutionary trajectories.}, } @article {pmid18939953, year = {2009}, author = {Ruaud, AF and Nilsson, L and Richard, F and Larsen, MK and Bessereau, JL and Tuck, S}, title = {The C. elegans P4-ATPase TAT-1 regulates lysosome biogenesis and endocytosis.}, journal = {Traffic (Copenhagen, Denmark)}, volume = {10}, number = {1}, pages = {88-100}, doi = {10.1111/j.1600-0854.2008.00844.x}, pmid = {18939953}, issn = {1600-0854}, mesh = {Adenosine Triphosphatases/genetics/*metabolism ; Animals ; Caenorhabditis elegans/genetics/*metabolism/ultrastructure ; Caenorhabditis elegans Proteins/genetics/*metabolism ; *Endocytosis ; Female ; Gene Expression Regulation ; Humans ; Intestinal Mucosa/metabolism ; Lysosomes/*enzymology/ultrastructure ; Microscopy, Electron ; Mutation/genetics ; *Organelle Biogenesis ; Phospholipid Transfer Proteins/genetics/*metabolism ; Phylogeny ; Protein Transport ; Time Factors ; Vacuoles/metabolism ; }, abstract = {P-type adenosine triphosphatases (ATPases) of the Drs2p family (P4-ATPases) are multipass transmembrane proteins required to generate and maintain phospholipid asymmetry in membrane bilayers. In Saccharomyces cerevisiae, several members of this family control distinct transport events within the endosomal and secretory pathways. Comparatively, little is known about the functions of P4-ATPases in multicellular organisms. In this study, we analyzed the role of the Caenorhabditis elegans Drs2p homologue transbilayer amphipath transporter (TAT)-1 in intracellular trafficking. tat-1 is expressed in many tissues including the intestine, the epidermis and the nervous system. In intestinal cells, tat-1 loss-of-function mutants accumulate large vacuoles of mixed endolysosomal identity positive for the lysosomal protein LMP-1. In addition, they lack the same class of storage granules as lmp-1 mutants, suggesting that part of the tat-1 phenotype might result from LMP-1 sequestration in an aberrant compartment. Epidermal cells mutant for tat-1 contain acidified giant hybrid multivesicular bodies probably corresponding to endolysosomal intermediate compartments or deficient lysosomes. Finally, TAT-1 is required for yolk uptake in oocytes and an early step of fluid-phase endocytosis in the intestine. Hence, TAT-1 is required at multiple steps of the endolysosomal pathway, at least in part by ensuring proper trafficking of cell-specific effector proteins.}, } @article {pmid18937373, year = {2008}, author = {Aanen, DK and Debets, AJ and de Visser, JA and Hoekstra, RF}, title = {The social evolution of somatic fusion.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {30}, number = {11-12}, pages = {1193-1203}, doi = {10.1002/bies.20840}, pmid = {18937373}, issn = {1521-1878}, mesh = {Animals ; *Biological Evolution ; Crosses, Genetic ; Genetics, Population ; Immune System ; Models, Biological ; Models, Genetic ; Models, Theoretical ; Polymorphism, Genetic ; Reproduction/*genetics/*physiology ; }, abstract = {The widespread potential for somatic fusion among different conspecific multicellular individuals suggests that such fusion is adaptive. However, because recognition of non-kin (allorecognition) usually leads to a rejection response, successful somatic fusion is limited to close kin. This is consistent with kin-selection theory, which predicts that the potential cost of fusion and the potential for somatic parasitism decrease with increasing relatedness. Paradoxically, however, Crozier found that, in the short term, positive-frequency-dependent selection eliminates the required genetic polymorphism at allorecognition loci. The 'Crozier paradox' may be solved if allorecognition is based on extrinsically balanced polymorphisms, for example at immune loci. Alternatively, the assumption of most models that self fusion is mutually beneficial is wrong. If fusion is on average harmful, selection will promote unconditional rejection. However, we propose that fusion within individuals is beneficial, selecting for the ability to fuse, but fusion between individuals on average costly, selecting for non-self recognition (rather than non-kin recognition). We discuss experimental data on fungi that are consistent with this hypothesis.}, } @article {pmid18937362, year = {2008}, author = {Engelstädter, J}, title = {Constraints on the evolution of asexual reproduction.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {30}, number = {11-12}, pages = {1138-1150}, doi = {10.1002/bies.20833}, pmid = {18937362}, issn = {1521-1878}, mesh = {Animals ; Centrosome/ultrastructure ; Chromosome Mapping ; Diploidy ; Female ; Genome ; Genomic Imprinting ; Haploidy ; Male ; Models, Biological ; Models, Genetic ; Parthenogenesis/genetics ; Plants ; Ploidies ; Reproduction, Asexual/*genetics ; }, abstract = {Sexual reproduction is almost ubiquitous among multicellular organisms even though it entails severe fitness costs. To resolve this apparent paradox, an extensive body of research has been devoted to identifying the selective advantages of recombination that counteract these costs. Yet, how easy is it to make the transition to asexual reproduction once sexual reproduction has been established for a long time? The present review approaches this question by considering factors that impede the evolution of parthenogenesis in animals. Most importantly, eggs need a diploid chromosome set in most species in order to develop normally. Next, eggs may need to be activated by sperm, and sperm may also contribute centrioles and other paternal factors to the zygote. Depending on how diploidy is achieved mechanistically, further problems may arise in offspring that stem from 'inbreeding depression' or inappropriate sex determination systems. Finally, genomic imprinting is another well-known barrier to the evolution of asexuality in mammals. Studies on species with occasional, deficient parthenogenesis indicate that the relative importance of these constraints may vary widely. The intimate evolutionary relations between haplodiploidy and parthenogenesis as well as implications for the clade selection hypothesis of the maintenance of sexual reproduction are also discussed.}, } @article {pmid18936483, year = {2008}, author = {Pace, JK and Gilbert, C and Clark, MS and Feschotte, C}, title = {Repeated horizontal transfer of a DNA transposon in mammals and other tetrapods.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {44}, pages = {17023-17028}, pmid = {18936483}, issn = {1091-6490}, support = {R01 GM077582/GM/NIGMS NIH HHS/United States ; R01 GM077582-02/GM/NIGMS NIH HHS/United States ; R01GM77582/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; DNA Transposable Elements/*genetics ; Databases, Genetic ; Evolution, Molecular ; *Gene Transfer, Horizontal ; Genome ; Humans ; Mammals/genetics ; Mice ; Molecular Sequence Data ; Phylogeny ; Rats ; }, abstract = {Horizontal transfer (HT) is central to the evolution of prokaryotic species. Selfish and mobile genetic elements, such as phages, plasmids, and transposons, are the primary vehicles for HT among prokaryotes. In multicellular eukaryotes, the prevalence and evolutionary significance of HT remain unclear. Here, we identified a set of DNA transposon families dubbed SPACE INVADERS (or SPIN) whose consensus sequences are approximately 96% identical over their entire length (2.9 kb) in the genomes of murine rodents (rat/mouse), bushbaby (prosimian primate), little brown bat (laurasiatherian), tenrec (afrotherian), opossum (marsupial), and two non-mammalian tetrapods (anole lizard and African clawed frog). In contrast, SPIN elements were undetectable in other species represented in the sequence databases, including 19 other mammals with draft whole-genome assemblies. This patchy distribution, coupled with the extreme level of SPIN identity in widely divergent tetrapods and the overall lack of selective constraint acting on these elements, is incompatible with vertical inheritance, but strongly indicative of multiple horizontal introductions. We show that these germline infiltrations likely occurred around the same evolutionary time (15-46 mya) and spawned some of the largest bursts of DNA transposon activity ever recorded in any species lineage (nearly 100,000 SPIN copies per haploid genome in tenrec). The process also led to the emergence of a new gene in the murine lineage derived from a SPIN transposase. In summary, HT of DNA transposons has contributed significantly to shaping and diversifying the genomes of multiple mammalian and tetrapod species.}, } @article {pmid18935972, year = {2009}, author = {Schierwater, B and de Jong, D and Desalle, R}, title = {Placozoa and the evolution of Metazoa and intrasomatic cell differentiation.}, journal = {The international journal of biochemistry & cell biology}, volume = {41}, number = {2}, pages = {370-379}, doi = {10.1016/j.biocel.2008.09.023}, pmid = {18935972}, issn = {1357-2725}, mesh = {Animals ; *Biological Evolution ; Cell Differentiation/genetics ; Phylogeny ; Placozoa/cytology/*genetics/ultrastructure ; }, abstract = {The multicellular Metazoa evolved from single-celled organisms (Protozoa) and usually - but not necessarily - consist of more cells than Protozoa. In all cases, and thus by definition, Metazoa possess more than one somatic cell type, i.e. they show-in sharp contrast to protists-intrasomatic differentiation. Placozoa have the lowest degree of intrasomatic variation; the number of somatic cell types according to text books is four (but see also Jakob W, Sagasser S, Dellaporta S, Holland P, Kuhn K, and Schierwater B. The Trox-2 Hox/ParaHox gene of Trichoplax (Placozoa) marks an epithelial boundary. Dev Genes Evol 2004;214:170-5). For this and several other reasons Placozoa have been regarded by many as the most basal metazoan phylum. Thus, the morphologically most simply organized metazoan animal, the placozoan Trichoplax adhaerens, resembles a unique model system for cell differentiation studies and also an intriguing model for a prominent "urmetazoon" hypotheses-the placula hypothesis. A basal position of Placozoa would provide answers to several key issues of metazoan-specific inventions (including for example different lines of somatic cell differentiation leading to organ development and axis formation) and would determine a root for unraveling their evolution. However, the phylogenetic relationships at the base of Metazoa are controversial and a basal position of Placozoa is not generally accepted (e.g. Schierwater B, DeSalle R. Can we ever identify the Urmetazoan? Integr Comp Biol 2007;47:670-76; DeSalle R, Schierwater B. An even "newer" animal phylogeny. Bioessays 2008;30:1043-47). Here we review and discuss (i) long-standing morphological evidence for the simple placozoan bauplan resembling an ancestral metazoan stage, (ii) some rapidly changing alternative hypotheses derived from molecular analyses, (iii) the surprising idea that triploblasts (Bilateria) and diploblasts may be sister groups, and (iv) the presence of genes involved in cell differentiation and signaling pathways in the placozoan genome.}, } @article {pmid18927580, year = {2008}, author = {Arendt, D}, title = {The evolution of cell types in animals: emerging principles from molecular studies.}, journal = {Nature reviews. Genetics}, volume = {9}, number = {11}, pages = {868-882}, doi = {10.1038/nrg2416}, pmid = {18927580}, issn = {1471-0064}, mesh = {Animals ; *Biological Evolution ; Cell Differentiation/*physiology ; Cell Lineage/genetics/*physiology ; DNA Fingerprinting ; Endocrine System/*cytology ; Immune System/*cytology ; Nervous System/*cytology ; Phylogeny ; }, abstract = {Cell types are fundamental units of multicellular life but their evolution is obscure. How did the first cell types emerge and become distinct in animal evolution? What were the sets of cell types that existed at important evolutionary nodes that represent eumetazoan or bilaterian ancestors? How did these ancient cell types diversify further during the evolution of organ systems in the descending evolutionary lines? The recent advent of cell type molecular fingerprinting has yielded initial insights into the evolutionary interrelationships of cell types between remote animal phyla and has allowed us to define some first principles of cell type diversification in animal evolution.}, } @article {pmid18926974, year = {2009}, author = {Cremer, S and Sixt, M}, title = {Analogies in the evolution of individual and social immunity.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {364}, number = {1513}, pages = {129-142}, pmid = {18926974}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Host-Parasite Interactions/genetics/immunology/physiology ; Insecta/*genetics/*immunology/physiology ; Models, Immunological ; Social Behavior ; }, abstract = {We compare anti-parasite defences at the level of multicellular organisms and insect societies, and find that selection by parasites at these two organisational levels is often very similar and has created a number of parallel evolutionary solutions in the host's immune response. The defence mechanisms of both individuals and insect colonies start with border defences to prevent parasite intake and are followed by soma defences that prevent the establishment and spread of the parasite between the body's cells or the social insect workers. Lastly, germ line defences are employed to inhibit infection of the reproductive tissue of organisms or the reproductive individuals in colonies. We further find sophisticated self/non-self-recognition systems operating at both levels, which appear to be vital in maintaining the integrity of the body or colony as a reproductive entity. We then expand on the regulation of immune responses and end with a contemplation of how evolution may shape the different immune components, both within and between levels. The aim of this review is to highlight common evolutionary principles acting in disease defence at the level of both individual organisms and societies, thereby linking the fields of physiological and ecological immunology.}, } @article {pmid18926910, year = {2008}, author = {Rokas, A}, title = {The molecular origins of multicellular transitions.}, journal = {Current opinion in genetics & development}, volume = {18}, number = {6}, pages = {472-478}, doi = {10.1016/j.gde.2008.09.004}, pmid = {18926910}, issn = {1879-0380}, mesh = {*Biological Evolution ; Eukaryotic Cells/*cytology ; *Evolution, Molecular ; Genome/*genetics ; *Phylogeny ; Protein Structure, Tertiary ; Transcription Factors/*genetics ; }, abstract = {Multicellularity has evolved multiple times independently from a variety of ancestral unicellular lineages. Past research on multicellularity was focused more on explaining why it was repeatedly invented and less so on the molecular foundations associated with each transition. Several recent comparative functional analyses of microbial unicellular and multicellular genomes have begun to throw considerable light on the molecular commonalities exhibited by independent multicellular transitions. These have enabled the delineation of the likely functional components of the genetic toolkit required for multicellular existence and to surprising discoveries, such as the presence of several toolkit components in unicellular lineages. The study of these toolkit proteins in a unicellular context has begun yielding insights into their ancestral functions and how they were coopted for multicellular development.}, } @article {pmid18922717, year = {2009}, author = {Perlman, RL}, title = {Life histories of pathogen populations.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {13}, number = {2}, pages = {121-124}, doi = {10.1016/j.ijid.2008.07.003}, pmid = {18922717}, issn = {1878-3511}, mesh = {Animals ; *Bacteria/growth & development/pathogenicity ; Biological Evolution ; Communicable Diseases/*etiology/transmission ; *Host-Pathogen Interactions/genetics/physiology ; Humans ; Life Cycle Stages ; Models, Biological ; *Parasites/growth & development/pathogenicity ; Population Dynamics ; Virulence/genetics ; *Viruses/growth & development/pathogenicity ; }, abstract = {The populations of pathogens in individual hosts have many of the characteristics of multicellular organisms, or individuals. These populations go through a life cycle within a host and they reproduce by founding daughter populations in new hosts. Natural selection shapes the life history characteristics of pathogen populations--life expectancy, trade-offs in the allocation of resources between growth, survival, and fecundity, and aging--in ways that maximize the reproductive fitness of the pathogens. In turn, these life history characteristics shape the natural histories of infectious diseases. Transmissibility and virulence may be thought of as properties of pathogen populations rather than as properties of the constituent microorganisms within these populations. The poor correlation of virulence with pathogen fitness is a major obstacle to the development of a theory of virulence. Consideration of the life histories of pathogen populations complements the traditional epidemiological focus on host populations and provides a valuable perspective for understanding human infectious diseases.}, } @article {pmid18852690, year = {2009}, author = {Maltepe, E and Saugstad, OD}, title = {Oxygen in health and disease: regulation of oxygen homeostasis--clinical implications.}, journal = {Pediatric research}, volume = {65}, number = {3}, pages = {261-268}, doi = {10.1203/PDR.0b013e31818fc83f}, pmid = {18852690}, issn = {1530-0447}, mesh = {Adaptation, Physiological/*physiology ; *Biological Evolution ; Free Radicals/metabolism/toxicity ; Homeostasis/*physiology ; Humans ; Hyperoxia/*physiopathology ; Hypoxia/*physiopathology ; Infant, Newborn ; *Models, Biological ; Oxidative Stress/physiology ; Oxygen/*metabolism/toxicity ; }, abstract = {Oxygen is critical for multicellular existence. Its reduction to water by the mitochondrial electron transport chain helps supply the metabolic demands of human life. The incompletely reduced, reactive oxygen byproducts of this reaction, however, can be quite toxic. In this review, we explore the mechanisms responsible for maintaining oxygen homeostasis and the consequences of their dysfunction. With an eye toward defining clinical care guidelines for the management of critically ill neonates, we present evidence describing the role of physiologic hypoxia during development and the adverse consequences of hyperoxia in-term as well as preterm infants.}, } @article {pmid18831774, year = {2008}, author = {Dunker, AK and Oldfield, CJ and Meng, J and Romero, P and Yang, JY and Chen, JW and Vacic, V and Obradovic, Z and Uversky, VN}, title = {The unfoldomics decade: an update on intrinsically disordered proteins.}, journal = {BMC genomics}, volume = {9 Suppl 2}, number = {Suppl 2}, pages = {S1}, pmid = {18831774}, issn = {1471-2164}, support = {R01 GM071714/GM/NIGMS NIH HHS/United States ; R01 LM007688/LM/NLM NIH HHS/United States ; GM071714-01A2/GM/NIGMS NIH HHS/United States ; R01 LM007688-01A1/LM/NLM NIH HHS/United States ; }, mesh = {Algorithms ; Alternative Splicing ; Amino Acid Sequence ; Binding Sites ; *Computational Biology ; Drug Design ; Humans ; Protein Conformation ; *Protein Folding ; Proteins/*chemistry/*metabolism ; Sequence Analysis, Protein ; Structure-Activity Relationship ; }, abstract = {BACKGROUND: Our first predictor of protein disorder was published just over a decade ago in the Proceedings of the IEEE International Conference on Neural Networks (Romero P, Obradovic Z, Kissinger C, Villafranca JE, Dunker AK (1997) Identifying disordered regions in proteins from amino acid sequence. Proceedings of the IEEE International Conference on Neural Networks, 1: 90-95). By now more than twenty other laboratory groups have joined the efforts to improve the prediction of protein disorder. While the various prediction methodologies used for protein intrinsic disorder resemble those methodologies used for secondary structure prediction, the two types of structures are entirely different. For example, the two structural classes have very different dynamic properties, with the irregular secondary structure class being much less mobile than the disorder class. The prediction of secondary structure has been useful. On the other hand, the prediction of intrinsic disorder has been revolutionary, leading to major modifications of the more than 100 year-old views relating protein structure and function. Experimentalists have been providing evidence over many decades that some proteins lack fixed structure or are disordered (or unfolded) under physiological conditions. In addition, experimentalists are also showing that, for many proteins, their functions depend on the unstructured rather than structured state; such results are in marked contrast to the greater than hundred year old views such as the lock and key hypothesis. Despite extensive data on many important examples, including disease-associated proteins, the importance of disorder for protein function has been largely ignored. Indeed, to our knowledge, current biochemistry books don't present even one acknowledged example of a disorder-dependent function, even though some reports of disorder-dependent functions are more than 50 years old. The results from genome-wide predictions of intrinsic disorder and the results from other bioinformatics studies of intrinsic disorder are demanding attention for these proteins.

RESULTS: Disorder prediction has been important for showing that the relatively few experimentally characterized examples are members of a very large collection of related disordered proteins that are wide-spread over all three domains of life. Many significant biological functions are now known to depend directly on, or are importantly associated with, the unfolded or partially folded state. Here our goal is to review the key discoveries and to weave these discoveries together to support novel approaches for understanding sequence-function relationships.

CONCLUSION: Intrinsically disordered protein is common across the three domains of life, but especially common among the eukaryotic proteomes. Signaling sequences and sites of posttranslational modifications are frequently, or very likely most often, located within regions of intrinsic disorder. Disorder-to-order transitions are coupled with the adoption of different structures with different partners. Also, the flexibility of intrinsic disorder helps different disordered regions to bind to a common binding site on a common partner. Such capacity for binding diversity plays important roles in both protein-protein interaction networks and likely also in gene regulation networks. Such disorder-based signaling is further modulated in multicellular eukaryotes by alternative splicing, for which such splicing events map to regions of disorder much more often than to regions of structure. Associating alternative splicing with disorder rather than structure alleviates theoretical and experimentally observed problems associated with the folding of different length, isomeric amino acid sequences. The combination of disorder and alternative splicing is proposed to provide a mechanism for easily "trying out" different signaling pathways, thereby providing the mechanism for generating signaling diversity and enabling the evolution of cell differentiation and multicellularity. Finally, several recent small molecules of interest as potential drugs have been shown to act by blocking protein-protein interactions based on intrinsic disorder of one of the partners. Study of these examples has led to a new approach for drug discovery, and bioinformatics analysis of the human proteome suggests that various disease-associated proteins are very rich in such disorder-based drug discovery targets.}, } @article {pmid18836084, year = {2008}, author = {Pérez, J and Castañeda-García, A and Jenke-Kodama, H and Müller, R and Muñoz-Dorado, J}, title = {Eukaryotic-like protein kinases in the prokaryotes and the myxobacterial kinome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {41}, pages = {15950-15955}, pmid = {18836084}, issn = {1091-6490}, mesh = {Bacterial Proteins/analysis ; Gene Duplication ; Myxococcales/*enzymology ; Phylogeny ; Prokaryotic Cells/*enzymology ; Protein Kinases/*analysis/chemistry/genetics ; Signal Transduction ; Synteny ; }, abstract = {Ser/Thr/Tyr kinases, which together comprise a major class of regulatory proteins in eukaryotes, were not believed to play an important role in prokaryotes until recently. However, our analysis of 626 prokaryotic genomes reveals that eukaryotic-like protein kinases (ELKs) are found in nearly two-thirds of the sequenced strains. We have identified 2697 ELKs, most of which are encoded by multicellular strains of the phyla Proteobacteria (Myxococcales), Actinobacteria, Cyanobacteria, and Chloroflexi, and 2 Acidobacteria and 1 Planctomycetes. Astonishingly, 7 myxobacterial strains together encode 892 ELKs, with 4 of the strains exhibiting a genomic ELK density similar to that observed in eukaryotes. Most myxobacterial ELKs show a modular organization in which the kinase domain is located at the N terminus. The C-terminal portion of the ELKs is highly diverse and often contains sequences with similarity to characterized domains, most of them involved in signaling mechanisms or in protein-protein interactions. However, many of these architectures are unique to the myxobacteria, an observation that suggests that this group exploits sophisticated and novel signal transduction systems. Phylogenetic reconstruction using the kinase domains revealed many orthologous sequence pairs and a huge number of gene duplications that probably occurred after speciation. Furthermore, studies of the microsynteny in the ELK-encoding regions reveal only low levels of synteny among Myxococcus xanthus, Plesiocystis pacifica, and Sorangium cellulosum. However, extensive similarities between M. xanthus, Stigmatella aurantiaca, and 3 Anaeromyxobacter strains were observed, indicating that they share regulatory pathways involving various ELKs.}, } @article {pmid18833755, year = {2008}, author = {Davey, ML and Tsuneda, A and Currah, RS}, title = {Evidence that the gemmae of Papulaspora sepedonioides are neotenous perithecia in the Melanosporales.}, journal = {Mycologia}, volume = {100}, number = {4}, pages = {626-635}, doi = {10.3852/08-001r}, pmid = {18833755}, issn = {0027-5514}, mesh = {Ascomycota/*classification/cytology/genetics/*growth & development ; Biological Evolution ; DNA, Fungal/genetics ; DNA, Ribosomal/genetics ; Fresh Water/microbiology ; Microscopy, Electron, Scanning ; Molecular Sequence Data ; Phylogeny ; }, abstract = {Papulaspora sepedonioides produces large multicellular gemmae with several, thick-walled central cells enclosed within a sheath of smaller thin-walled cells. Phylogenetic analysis of the large subunit rDNA indicates P. sepedonioides has affinities to the Melanosporales (Hypocreomycetidae). The development of gemmae in P. sepedonioides was characterized by light and scanning and transmission electron microscopy and was similar to previous ontogenetic studies of ascoma development in the Melanosporales. However instead of giving rise to ascogenous tissues the central cells of the incipient gemma became darkly pigmented, thick walled and filled with lipid globules while the contents of the sheath cells autolysed, leaving them empty and deflated at maturity. Both central cells and pre-autolytic sheath cells produced both germ tubes and new gemmae primordia, suggesting microcyclic conidiogenesis occurs in this species. Mature gemmae were non-deciduous or seceded by schizolytic secession and appear to have both perennating and disseminative potential. The evolution of these neotenous perithecial propagules may be driven by life-history and ecological factors selecting for functional versatility.}, } @article {pmid18832373, year = {2008}, author = {Castro, MA and Dalmolin, RJ and Moreira, JC and Mombach, JC and de Almeida, RM}, title = {Evolutionary origins of human apoptosis and genome-stability gene networks.}, journal = {Nucleic acids research}, volume = {36}, number = {19}, pages = {6269-6283}, pmid = {18832373}, issn = {1362-4962}, mesh = {Animals ; Apoptosis/*genetics ; Computational Biology ; *Evolution, Molecular ; *Gene Regulatory Networks ; Genes, Lethal ; Genes, Neoplasm ; Genome, Human ; *Genomic Instability ; Humans ; Mice ; Saccharomyces cerevisiae/genetics ; }, abstract = {Apoptosis is essential for complex multicellular organisms and its failure is associated with genome instability and cancer. Interactions between apoptosis and genome-maintenance mechanisms have been extensively documented and include transactivation-independent and -dependent functions, in which the tumor-suppressor protein p53 works as a 'molecular node' in the DNA-damage response. Although apoptosis and genome stability have been identified as ancient pathways in eukaryote phylogeny, the biological evolution underlying the emergence of an integrated system remains largely unknown. Here, using computational methods, we reconstruct the evolutionary scenario that linked apoptosis with genome stability pathways in a functional human gene/protein association network. We found that the entanglement of DNA repair, chromosome stability and apoptosis gene networks appears with the caspase gene family and the antiapoptotic gene BCL2. Also, several critical nodes that entangle apoptosis and genome stability are cancer genes (e.g. ATM, BRCA1, BRCA2, MLH1, MSH2, MSH6 and TP53), although their orthologs have arisen in different points of evolution. Our results demonstrate how genome stability and apoptosis were co-opted during evolution recruiting genes that merge both systems. We also provide several examples to exploit this evolutionary platform, where we have judiciously extended information on gene essentiality inferred from model organisms to human.}, } @article {pmid18828675, year = {2008}, author = {Tonikian, R and Zhang, Y and Sazinsky, SL and Currell, B and Yeh, JH and Reva, B and Held, HA and Appleton, BA and Evangelista, M and Wu, Y and Xin, X and Chan, AC and Seshagiri, S and Lasky, LA and Sander, C and Boone, C and Bader, GD and Sidhu, SS}, title = {A specificity map for the PDZ domain family.}, journal = {PLoS biology}, volume = {6}, number = {9}, pages = {e239}, pmid = {18828675}, issn = {1545-7885}, mesh = {Amino Acid Sequence ; Animals ; Binding Sites/genetics ; Caenorhabditis elegans Proteins/*analysis/chemistry/classification/*genetics ; Humans ; Membrane Proteins/chemistry/genetics/metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutation ; *PDZ Domains ; Peptides/analysis/genetics ; Phylogeny ; Protein Structure, Secondary ; Proteome/*analysis ; Tumor Suppressor Proteins/chemistry/genetics/metabolism ; Viral Proteins/genetics/metabolism ; }, abstract = {PDZ domains are protein-protein interaction modules that recognize specific C-terminal sequences to assemble protein complexes in multicellular organisms. By scanning billions of random peptides, we accurately map binding specificity for approximately half of the over 330 PDZ domains in the human and Caenorhabditis elegans proteomes. The domains recognize features of the last seven ligand positions, and we find 16 distinct specificity classes conserved from worm to human, significantly extending the canonical two-class system based on position -2. Thus, most PDZ domains are not promiscuous, but rather are fine-tuned for specific interactions. Specificity profiling of 91 point mutants of a model PDZ domain reveals that the binding site is highly robust, as all mutants were able to recognize C-terminal peptides. However, many mutations altered specificity for ligand positions both close and far from the mutated position, suggesting that binding specificity can evolve rapidly under mutational pressure. Our specificity map enables the prediction and prioritization of natural protein interactions, which can be used to guide PDZ domain cell biology experiments. Using this approach, we predicted and validated several viral ligands for the PDZ domains of the SCRIB polarity protein. These findings indicate that many viruses produce PDZ ligands that disrupt host protein complexes for their own benefit, and that highly pathogenic strains target PDZ domains involved in cell polarity and growth.}, } @article {pmid18826374, year = {2008}, author = {Melendez, AJ and Tay, HK}, title = {Phagocytosis: a repertoire of receptors and Ca(2+) as a key second messenger.}, journal = {Bioscience reports}, volume = {28}, number = {5}, pages = {287-298}, doi = {10.1042/BSR20080082}, pmid = {18826374}, issn = {0144-8463}, support = {G0700794/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Calcium/*metabolism ; Calcium Signaling/*physiology ; Cytoskeleton/*metabolism ; Humans ; Immunity, Innate/physiology ; Phagocytosis/*physiology ; Receptors, Cell Surface/*metabolism ; }, abstract = {Receptor-mediated phagocytosis is a complex process that mediates the internalization, by a cell, of other cells and large particles; this is an important physiological event not only in mammals, but in a wide diversity of organisms. Of simple unicellular organisms that use phagocytosis to extract nutrients, to complex metazoans in which phagocytosis is essential for the innate defence system, as a first line of defence against invading pathogens, as well as for the clearance of damaged, dying or dead cells. Evolution has armed multicellular organisms with a range of receptors expressed on many cells that serve as the molecular basis to bring about phagocytosis, regardless of the organism or the specific physiological event concerned. Key to all phagocytic processes is the finely controlled rearrangement of the actin cytoskeleton, in which Ca(2+) signals play a major role. Ca(2+) is involved in cytoskeletal changes by affecting the actions of a number of contractile proteins, as well as being a cofactor for the activation of a number of intracellular signalling molecules, which are known to play important roles during the initiation, progression and resolution of the phagocytic process. In mammals, the requirement of Ca(2+) for the initial steps in phagocytosis, and the subsequent phagosome maturation, can be quite different depending on the type of cell and on the type of receptor that is driving phagocytosis. In this review we discuss the different receptors that mediate professional and non-professional phagocytosis, and discuss the role of Ca(2+) in the different steps of this complex process.}, } @article {pmid18822659, year = {2007}, author = {Burian, RM}, title = {On microRNA and the need for exploratory experimentation in post-genomic molecular biology.}, journal = {History and philosophy of the life sciences}, volume = {29}, number = {3}, pages = {285-311}, pmid = {18822659}, issn = {0391-9714}, mesh = {Genome, Human/*genetics ; Genomics ; Humans ; MicroRNAs/*genetics ; Molecular Biology/*trends ; Time Factors ; }, abstract = {This paper is devoted to an examination of the discovery, characterization, and analysis of the functions of microRNAs, which also serves as a vehicle for demonstrating the importance of exploratory experimentation in current (post-genomic) molecular biology. The material on microRNAs is important in its own right: it provides important insight into the extreme complexity of regulatory networks involving components made of DNA, RNA, and protein. These networks play a central role in regulating development of multicellular organisms and illustrate the importance of epigenetic as well as genetic systems in evolution and development. The examination of these matters yields principled arguments for the historicity of the functions of key biological molecules and for the indispensability of exploratory experimentation in contemporary molecular biology as well as some insight into the complex interplay between exploratory experimentation and hypothesis-driven science. This latter result is not only important for philosophy of science, but also of practical importance for the evaluation of grant proposals, although the elaboration of this latter claim must be left for another occasion.}, } @article {pmid18820252, year = {2008}, author = {Domazet-Loso, T and Tautz, D}, title = {An ancient evolutionary origin of genes associated with human genetic diseases.}, journal = {Molecular biology and evolution}, volume = {25}, number = {12}, pages = {2699-2707}, pmid = {18820252}, issn = {1537-1719}, mesh = {Disease/*genetics ; *Evolution, Molecular ; Genome, Human ; Humans ; Multifactorial Inheritance ; }, abstract = {Several thousand genes in the human genome have been linked to a heritable genetic disease. The majority of these appear to be nonessential genes (i.e., are not embryonically lethal when inactivated), and one could therefore speculate that they are late additions in the evolutionary lineage toward humans. Contrary to this expectation, we find that they are in fact significantly overrepresented among the genes that have emerged during the early evolution of the metazoa. Using a phylostratigraphic approach, we have studied the evolutionary emergence of such genes at 19 phylogenetic levels. The majority of disease genes was already present in the eukaryotic ancestor, and the second largest number has arisen around the time of evolution of multicellularity. Conversely, genes specific to the mammalian lineage are highly underrepresented. Hence, genes involved in genetic diseases are not simply a random subset of all genes in the genome but are biased toward ancient genes.}, } @article {pmid18818927, year = {2009}, author = {Kou, Y and Qiu, D and Wang, L and Li, X and Wang, S}, title = {Molecular analyses of the rice tubby-like protein gene family and their response to bacterial infection.}, journal = {Plant cell reports}, volume = {28}, number = {1}, pages = {113-121}, pmid = {18818927}, issn = {0721-7714}, mesh = {Evolution, Molecular ; Gene Expression Regulation, Plant ; Genes, Plant ; Host-Pathogen Interactions ; *Multigene Family ; Oryza/*genetics/metabolism/microbiology ; Phylogeny ; Plant Diseases/*genetics ; Plant Proteins/genetics/*metabolism ; RNA, Plant/genetics ; Sequence Alignment ; Xanthomonas/*pathogenicity ; }, abstract = {Tubby-like protein family has been identified in various multicellular organisms, indicating its fundamental functions in the organisms. However, the roles of plant tubby-like proteins are unknown. In this study, we have defined the tubby-like protein gene (OsTLP) family with 14 members in rice. Most of the OsTLPs harbor a tubby domain in their carboxyl terminus and an F-box domain in the amino terminus. The expression of all the OsTLPs was induced on infection of Xanthomonas oryzae pv. oryzae, which causes bacterial blight, one of the most devastating diseases of rice worldwide. The maximal expression levels were observed at 2-8 h after infection for all the genes. Eight of the 14 OsTLPs were also responsive to wounding. All the OsTLPs showed differential expression in different tissues at different developmental stages. However, four pairs of the 14 OsTLPs, with each pair having high sequence similarity and distributing on the similar position of different chromosomes, showed similar expression pattern in different tissues, indicating their direct relationship in evolution. These results suggest that the OsTLP family is involved in host-pathogen interaction and it may be also associated with other physiological and developmental activities.}, } @article {pmid18797928, year = {2008}, author = {Reintamm, T and Kuusksalu, A and Metsis, M and Päri, M and Vallmann, K and Lopp, A and Justesen, J and Kelve, M}, title = {Sponge OAS has a distinct genomic structure within the 2-5A synthetase family.}, journal = {Molecular genetics and genomics : MGG}, volume = {280}, number = {5}, pages = {453-466}, pmid = {18797928}, issn = {1617-4615}, mesh = {2',5'-Oligoadenylate Synthetase/*genetics/metabolism ; Amino Acid Sequence ; Animals ; Base Sequence ; DNA Primers/chemistry ; Evolution, Molecular ; Exons/*genetics ; Genome ; Introns/*genetics ; Molecular Sequence Data ; *Multigene Family ; Phylogeny ; Polymerase Chain Reaction ; Porifera/enzymology/*genetics ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Vertebrates ; }, abstract = {2',5'-Oligoadenylate synthetases (2-5A synthetases, OAS) are enzymes that play an important role in the interferon-induced antiviral defense mechanisms in mammals. Sponges, the evolutionarily lowest multicellular animals, also possess OAS; however, their function is presently unclear. Low homology between primary structures of 2-5A synthetases from vertebrates and sponges renders their evolutionary relationship obscure. The genomic structure of vertebrate OASs has been thoroughly examined, making it possible to elucidate molecular evolution and expansion of this gene family. Until now, no OAS gene structure was available from sponges to compare it with the corresponding genes from higher organisms. In the present work, we determined the exon/intron structure of the OAS gene from the marine sponge Geodia cydonium and found it to be completely different from the strictly conserved exon/intron pattern of the OAS genes from vertebrates. This finding was corroborated by the analysis of OAS genes from another sponge, Amphimedon queenslandica, whose genome was recently sequenced. Our data suggest that vertebrate and sponge OAS genes have no direct common intron-containing ancestor and two (sub)types of OAS may be discriminated. This study opens new perspectives for understanding the phylogenesis and evolution of 2-5A synthetases as well as functional aspects of this multigene family.}, } @article {pmid18768474, year = {2008}, author = {Page, MJ and Di Cera, E}, title = {Evolution of peptidase diversity.}, journal = {The Journal of biological chemistry}, volume = {283}, number = {44}, pages = {30010-30014}, pmid = {18768474}, issn = {0021-9258}, support = {HL49413/HL/NHLBI NIH HHS/United States ; HL58141/HL/NHLBI NIH HHS/United States ; HL73813/HL/NHLBI NIH HHS/United States ; }, mesh = {Databases, Protein ; Evolution, Molecular ; Genome ; Genome, Archaeal ; Genome, Bacterial ; Humans ; Hydrolases/chemistry ; Peptide Hydrolases/*chemistry ; Proteins/chemistry ; Sequence Analysis, Protein ; Species Specificity ; Trypsin/chemistry ; }, abstract = {A wide variety of peptidases associate with vital biological pathways, but the origin and evolution of their tremendous diversity are poorly defined. Application of the MEROPS classification to a comprehensive set of genomes yields a simple pattern of peptidase distribution and provides insight into the organization of proteolysis in all forms of life. Unexpectedly, a near ubiquitous core set of peptidases is shown to contain more types than those unique to higher multicellular organisms. From this core group, an array of eukaryote-specific peptidases evolved to yield well known intracellular and extracellular processes. The paucity of peptidase families unique to higher metazoa suggests gains in proteolytic network complexity required a limited number of biochemical inventions. These findings provide a framework for deeper investigation into the evolutionary forces that shaped each peptidase family and a roadmap to develop a timeline for their expansion as an interconnected system.}, } @article {pmid18764950, year = {2008}, author = {Bailly, X and Vanin, S and Chabasse, C and Mizuguchi, K and Vinogradov, SN}, title = {A phylogenomic profile of hemerythrins, the nonheme diiron binding respiratory proteins.}, journal = {BMC evolutionary biology}, volume = {8}, number = {}, pages = {244}, pmid = {18764950}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; Annelida/*genetics ; Archaea/*genetics ; Archaeal Proteins/genetics ; Bacteria/*genetics ; Bacterial Proteins/genetics ; Bayes Theorem ; Evolution, Molecular ; Exons ; Genes, Archaeal ; Genes, Bacterial ; Genome ; Hemerythrin/*genetics ; Introns ; Molecular Sequence Data ; *Phylogeny ; RNA/genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {BACKGROUND: Hemerythrins, are the non-heme, diiron binding respiratory proteins of brachiopods, priapulids and sipunculans; they are also found in annelids and bacteria, where their functions have not been fully elucidated.

RESULTS: A search for putative Hrs in the genomes of 43 archaea, 444 bacteria and 135 eukaryotes, revealed their presence in 3 archaea, 118 bacteria, several fungi, one apicomplexan, a heterolobosan, a cnidarian and several annelids. About a fourth of the Hr sequences were identified as N- or C-terminal domains of chimeric, chemotactic gene regulators. The function of the remaining single domain bacterial Hrs remains to be determined. In addition to oxygen transport, the possible functions in annelids have been proposed to include cadmium-binding, antibacterial action and immunoprotection. A Bayesian phylogenetic tree revealed a split into two clades, one encompassing archaea, bacteria and fungi, and the other comprising the remaining eukaryotes. The annelid and sipunculan Hrs share the same intron-exon structure, different from that of the cnidarian Hr.

CONCLUSION: The phylogenomic profile of Hrs demonstrated a limited occurrence in bacteria and archaea and a marked absence in the vast majority of multicellular organisms. Among the metazoa, Hrs have survived in a cnidarian and in a few protostome groups; hence, it appears that in metazoans the Hr gene was lost in deuterostome ancestor(s) after the radiata/bilateria split. Signal peptide sequences in several Hirudinea Hrs suggest for the first time, the possibility of extracellular localization. Since the alpha-helical bundle is likely to have been among the earliest protein folds, Hrs represent an ancient family of iron-binding proteins, whose primary function in bacteria may have been that of an oxygen sensor, enabling aerophilic or aerophobic responses. Although Hrs evolved to function as O2 transporters in brachiopods, priapulids and sipunculans, their function in annelids remains to be elucidated. Overall Hrs exhibit a considerable lack of evolutionary success in metazoans.}, } @article {pmid18757919, year = {2008}, author = {Lynch, M}, title = {The cellular, developmental and population-genetic determinants of mutation-rate evolution.}, journal = {Genetics}, volume = {180}, number = {2}, pages = {933-943}, pmid = {18757919}, issn = {0016-6731}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; GM36827/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Animals ; *Evolution, Molecular ; Humans ; *Mutation ; Selection, Genetic ; }, abstract = {Although the matter has been subject to considerable theoretical study, there are numerous open questions regarding the mechanisms driving the mutation rate in various phylogenetic lineages. Most notably, empirical evidence indicates that mutation rates are elevated in multicellular species relative to unicellular eukaryotes and prokaryotes, even on a per-cell division basis, despite the need for the avoidance of somatic damage and the accumulation of germline mutations. Here it is suggested that multicellularity discourages selection against weak mutator alleles for reasons associated with both the cellular and the population-genetic environments, thereby magnifying the vulnerability to somatic mutations (cancer) and increasing the risk of extinction from the accumulation of germline mutations. Moreover, contrary to common belief, a cost of fidelity need not be invoked to explain the lower bound to observed mutation rates, which instead may simply be set by the inability of selection to advance very weakly advantageous antimutator alleles in finite populations.}, } @article {pmid18718841, year = {2008}, author = {Sawarkar, R and Roy, N and Rao, S and Raman, S and Venketesh, S and Suguna, K and Tatu, U}, title = {Heat shock protein 90 regulates development in Dictyostelium discoideum.}, journal = {Journal of molecular biology}, volume = {383}, number = {1}, pages = {24-35}, doi = {10.1016/j.jmb.2008.08.006}, pmid = {18718841}, issn = {1089-8638}, mesh = {Adenosine Triphosphatases/genetics/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Benzoquinones/pharmacology ; Binding Sites ; Cloning, Molecular ; Crystallization ; DNA, Protozoan/genetics ; Dictyostelium/drug effects/genetics/*growth & development/*metabolism ; Genes, Protozoan ; HSP90 Heat-Shock Proteins/antagonists & inhibitors/chemistry/genetics/*metabolism ; Kinetics ; Lactams, Macrocyclic/pharmacology ; Models, Molecular ; Phenotype ; Protein Isoforms/antagonists & inhibitors/chemistry/genetics/metabolism ; Protein Structure, Tertiary ; Protozoan Proteins/antagonists & inhibitors/chemistry/genetics/*metabolism ; Recombinant Proteins/chemistry/genetics/metabolism ; Saccharomyces cerevisiae Proteins/antagonists & inhibitors/metabolism ; Species Specificity ; }, abstract = {Cytosolic heat shock protein 90 (Hsp90) has been implicated in diverse biological processes such as protein folding, cell cycle control, signal transduction, development, and morphological evolution. Model systems available for studying Hsp90 function either allow ease of manipulation for biochemical studies or facilitate a phenomenological study of its role in influencing phenotype. In this work, we have explored the use of the cellular slime mold Dictyostelium discoideum to examine cellular functions of Hsp90 in relation to its multicellular development. In addition to cloning, purification, biochemical characterization, and examination of its crystal structure, our studies, using a pharmacological inhibitor of Hsp90, demonstrate a role for the cytoplasmic isoform (HspD) in D. discoideum development. Inhibition of HspD function using geldanamycin (GA) resulted in delayed aggregation and arrest of D. discoideum development at the 'mound' stage. Crystal structure of the amino-terminal domain of HspD showed a binding pocket similar to that described for yeast Hsp90. Fluorescence spectroscopy, as well as GA-coupled beads affinity pulldown, confirmed a specific interaction between HspD and GA. The results presented here provide an important insight into the function of HspD in D. discoideum development and emphasize the potential of the cellular slime mold to serve as an effective model for studying the many roles of Hsp90 at cellular and organismal levels.}, } @article {pmid18713893, year = {2008}, author = {Sonner, JM}, title = {A hypothesis on the origin and evolution of the response to inhaled anesthetics.}, journal = {Anesthesia and analgesia}, volume = {107}, number = {3}, pages = {849-854}, pmid = {18713893}, issn = {1526-7598}, support = {R01 GM069379/GM/NIGMS NIH HHS/United States ; R01 GM069379-04/GM/NIGMS NIH HHS/United States ; }, mesh = {Anesthesiology/methods ; Anesthetics, Inhalation/*therapeutic use ; Animals ; Biological Evolution ; Humans ; *Ion Channel Gating ; Ion Channels/metabolism ; Models, Biological ; Models, Theoretical ; Saccharomyces cerevisiae/drug effects ; }, abstract = {In this article, I present an evolutionary explanation for why organisms respond to inhaled anesthetics. It is conjectured that organisms today respond to inhaled anesthetics owing to the sensitivity of ion channels to inhaled anesthetics, which in turn has arisen by common descent from ancestral, anesthetic-sensitive ion channels in one-celled organisms (i.e., that the response to anesthetics did not arise as an adaptation of the nervous system, but rather of ion channels that preceded the origin of multicellularity). This sensitivity may have been refined by continuing selection at synapses in multicellular organisms. In particular, it is hypothesized that 1) the beneficial trait that was selected for in one-celled organisms was the coordinated response of ion channels to compounds that were present in the environment, which influenced the conformational equilibrium of ion channels; 2) this coordinated response prevented the deleterious consequences of entry of positive charges into the cell, thereby increasing the fitness of the organism; and 3) these compounds (which may have included organic anions, cations, and zwitterions as well as uncharged compounds) mimicked inhaled anesthetics in that they were interfacially active, and modulated ion channel function by altering bilayer properties coupled to channel function. The proposed hypothesis is consistent with known properties of inhaled anesthetics. In addition, it leads to testable experimental predictions of nonvolatile compounds having anesthetic-like modulatory effects on ion channels and in animals, including endogenous compounds that may modulate ion channel function in health and disease. The latter included metabolites that are increased in some types of end-stage organ failure, and genetic metabolic diseases. Several of these predictions have been tested and proved to be correct.}, } @article {pmid18713461, year = {2008}, author = {Hochberg, ME and Rankin, DJ and Taborsky, M}, title = {The coevolution of cooperation and dispersal in social groups and its implications for the emergence of multicellularity.}, journal = {BMC evolutionary biology}, volume = {8}, number = {}, pages = {238}, pmid = {18713461}, issn = {1471-2148}, mesh = {*Biological Evolution ; *Cooperative Behavior ; *Models, Genetic ; Phenotype ; Population Dynamics ; *Selection, Genetic ; }, abstract = {BACKGROUND: Recent work on the complexity of life highlights the roles played by evolutionary forces at different levels of individuality. One of the central puzzles in explaining transitions in individuality for entities ranging from complex cells, to multicellular organisms and societies, is how different autonomous units relinquish control over their functions to others in the group. In addition to the necessity of reducing conflict over effecting specialized tasks, differentiating groups must control the exploitation of the commons, or else be out-competed by more fit groups.

RESULTS: We propose that two forms of conflict - access to resources within groups and representation in germ line - may be resolved in tandem through individual and group-level selective effects. Specifically, we employ an optimization model to show the conditions under which different within-group social behaviors (cooperators producing a public good or cheaters exploiting the public good) may be selected to disperse, thereby not affecting the commons and functioning as germ line. We find that partial or complete dispersal specialization of cheaters is a general outcome. The propensity for cheaters to disperse is highest with intermediate benefit:cost ratios of cooperative acts and with high relatedness. An examination of a range of real biological systems tends to support our theory, although additional study is required to provide robust tests.

CONCLUSION: We suggest that trait linkage between dispersal and cheating should be operative regardless of whether groups ever achieve higher levels of individuality, because individual selection will always tend to increase exploitation, and stronger group structure will tend to increase overall cooperation through kin selected benefits. Cheater specialization as dispersers offers simultaneous solutions to the evolution of cooperation in social groups and the origin of specialization of germ and soma in multicellular organisms.}, } @article {pmid18707357, year = {2001}, author = {Roze, D and Michod, RE}, title = {Mutation, multilevel selection, and the evolution of propagule size during the origin of multicellularity.}, journal = {The American naturalist}, volume = {158}, number = {6}, pages = {638-654}, doi = {10.1086/323590}, pmid = {18707357}, issn = {1537-5323}, abstract = {Evolutionary transitions require the organization of genetic variation at two (or more) levels of selection so that fitness heritability may emerge at the new level. In this article, we consider the consequences for fitness variation and heritability of two of the main modes of reproduction used in multicellular organisms: vegetative reproduction and single-cell reproduction. We study a model where simple cell colonies reproduce by fragments or propagules of differing size, with mutations occurring during colony growth. Mutations are deleterious at the colony level but can be advantageous or deleterious at the cell level ("selfish" or "uniformly deleterious" mutants). Fragment size affects fitness in two ways: through a direct effect on adult group size (which in turn affects fitness) and by affecting the within- and between-group variances and opportunity for selection on mutations at the two levels. We show that the evolution of fragment size is determined primarily by its direct effects on group size except when mutations are selfish. When mutations are selfish, smaller propagule size may be selected, including single-cell reproduction, even though smaller propagule size has a direct fitness cost by virtue of producing smaller organisms, that is, smaller adult cell groups.}, } @article {pmid18669302, year = {2008}, author = {Bogdanov, IuF}, title = {[Evolution of meiosis of unicellulate and multicellular eucaryotes. Aromorphosis at the cellular level].}, journal = {Zhurnal obshchei biologii}, volume = {69}, number = {2}, pages = {102-117}, pmid = {18669302}, issn = {0044-4596}, mesh = {Animals ; *Biological Evolution ; Centromere/physiology/ultrastructure ; Chromatids/physiology/ultrastructure ; Kinetochores/*physiology/ultrastructure ; Meiosis/*physiology ; Recombination, Genetic/*physiology ; Synaptonemal Complex/*physiology/ultrastructure ; }, abstract = {An attempt was undertaken to apply the concept elaborated for the evolution of multicellular organisms to that of unicellular eucaryotes. The latter's meiosis was formed on the basis of combination on three intracellular processes: 1) homologous DNA recombination, 2) chromosome disjunction with the assistance of mitotic apparatus, and 3) formation of "linear" chromosome elements consisting of specific proteins. Mechanism of homologous chromosome recombination was inherited from the archibacteria, while both the mitotic apparatus and "linear" chromosome elements emerged de novo. These elements appeared (resulting from appearance of the meiosis-specific proteins) as a complication of cohesion filaments, arising at the boundary between the sister chromatids after DNA replication. Homologous chromosome recombination made it possible for the chromosomes of diploid organisms to join pairwise by means of Holliday structures, while temporary blocking of hydrolysis of the linear elements at centromeres made it possible for the kinetochores to acquire unipolarity and for the sister chromatids to move to the same pole. All these provided for reduction of the chromosome number. Such a type of the reduction of chromosome number was retained by the extant imperfect ascomycetes Schizosaccharomyces pombe and Aspergillus nidulans, and by the infusorian Tetrahyrmena thermophila. It was the derivative of specific proteins, i.e. synaptonemal complexes (SCs). that appeared to be aromorphosis; they came to existence due to the pairwise joining of the chromosome "linear" elements by means of protein "zipper". The SCs join homologous chromosomes temporarily at the prophase of meiotic reduction division, thus optimizing condition for the crossing over and chiasma formation. The latter and the kinetochore unipolarity both provide for the chromosome disjunction. Kinetochore unipolarity is caused by the protein shugoshin which appears at meiotic prophase I and blocks cohesin hydrolysis at centromeres when anaphase I begins. This type of reductional division became the basis of the classical meiosis in the overwhelming majority of unicellular and multicellular organisms over all eucaryote kingdoms.}, } @article {pmid18662703, year = {2008}, author = {Otsuka, J}, title = {A theoretical approach to the large-scale evolution of multicellularity and cell differentiation.}, journal = {Journal of theoretical biology}, volume = {255}, number = {1}, pages = {129-136}, doi = {10.1016/j.jtbi.2008.07.006}, pmid = {18662703}, issn = {1095-8541}, mesh = {Animals ; Cell Communication/physiology ; Cell Differentiation/genetics ; Energy Metabolism ; *Environment ; *Evolution, Molecular ; *Genome ; Models, Biological ; Mutation ; *Origin of Life ; Thermodynamics ; }, abstract = {In contrast to Darwinian evolution in which organisms have been selected by the instantaneous judgment of advantage or disadvantage for a mutated gene, the large-scale evolution of multicellular organisms by drastic changes in their genomes to produce new genes is theoretically formulated on the basis of the new concept of 'biological activity'. The 'biological activity' of an organism is a macroscopic quantity determined by its whole genome and the environment, consisting of three terms; the energy acquired from the outside, the energy stored in the form of bio-molecules, and the systematization of multicellularity as well as of organizing genes and their products. The acquired energy minus stored energy is lost as heat, and the entropy production by the heat must compensate for the entropy reduction owing to the systematization in the organism. Under the boundary determined by this thermodynamic law, the organisms, which experienced gene duplication to produce new genes for multicellularity and cell differentiation, first decline to be minor members in a population by the increase in the energy to be stored and by the advanced systematization of cell differentiation. If the acquired energy is raised by the cooperative action of newly differentiated cells with the pre-existing types of cells, however, the 'biological activity' of this new style of organism can be recovered. The new style of organism generated through this evolutionary process does not necessarily expel the old style of organism to extinction but can coexist by choosing different material and energy resources. Moreover, this theory of large-scale evolution not only explains the punctuated mode of evolution indicated by paleontology but also reproduces the divergence of body plans observed in Triploblastica and Tracheophyta.}, } @article {pmid18661101, year = {2008}, author = {Giuliani, A and Pirri, G and Bozzi, A and Di Giulio, A and Aschi, M and Rinaldi, AC}, title = {Antimicrobial peptides: natural templates for synthetic membrane-active compounds.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {65}, number = {16}, pages = {2450-2460}, doi = {10.1007/s00018-008-8188-x}, pmid = {18661101}, issn = {1420-682X}, mesh = {Animals ; Anti-Infective Agents/*pharmacology ; Antimicrobial Cationic Peptides/chemistry/*metabolism ; Biomimetic Materials/chemistry ; Cell Membrane/*drug effects/*metabolism ; Humans ; Protein Folding ; }, abstract = {The innate immunity of multicellular organisms relies in large part on the action of antimicrobial peptides (AMPs) to resist microbial invasion. Crafted by evolution into an extremely diversified array of sequences and folds, AMPs do share a common amphiphilic 3-D arrangement. This feature is directly linked with a common mechanism of action that predominantly (although not exclusively) develops upon interaction of peptides with cell membranes of target cells. This minireview reports on current understanding of the modes of interaction of AMPs with biological and model membranes, especially focusing on recent insights into the folding and oligomerization requirements of peptides to bind and insert into lipid membranes and exert their antibiotic effects. Given the potential of AMPs to be developed into a new class of anti-infective agents, emphasis is placed on how the information on peptide-membrane interactions could direct the design and selection of improved biomimetic synthetic peptides with antibiotic properties.}, } @article {pmid18652070, year = {2007}, author = {Ellington, WR and Suzuki, T}, title = {Early evolution of the creatine kinase gene family and the capacity for creatine biosynthesis and membrane transport.}, journal = {Sub-cellular biochemistry}, volume = {46}, number = {}, pages = {17-26}, doi = {10.1007/978-1-4020-6486-9_2}, pmid = {18652070}, issn = {0306-0225}, mesh = {Animals ; Biological Transport, Active/physiology ; Cell Membrane/*enzymology/genetics ; Creatine/*biosynthesis/genetics ; Creatine Kinase/genetics/*metabolism ; *Evolution, Molecular ; Humans ; Multigene Family/*physiology ; }, abstract = {The creatine kinase (CK)/phosphocreatine (PCr) energy buffering system is widespread in animal groups. Recent genomic sequencing and experimental results support the view that the capacity for creatine biosynthesis and membrane transport may have evolved quite early, perhaps coincident with CK. Conventional wisdom would suggest that CK evolved from an ancestral protein most similar to the CK homologue, arginine kinase. This early CK gene subsequently diverged into the cytoplasmic, mitochondrial and flagellar CK gene families. It is now clear that both the mitochondrial and cytoplasmic-flagellar genes were present prior to the divergence of sponges from the multi-cellular animal (metazoan) lineage, possibly as long as a billion years ago. Sponges constitute the most ancient, extant metazoan group. It is likely that the primary function of the CK-PCr system in these primitive animals was to mitigate reaction-diffusion constraints in highly polarized cells such as spermatozoa and choanocytes, the water current generating cells in sponges.}, } @article {pmid18647343, year = {2008}, author = {Karppinen, K and Hokkanen, J and Mattila, S and Neubauer, P and Hohtola, A}, title = {Octaketide-producing type III polyketide synthase from Hypericum perforatum is expressed in dark glands accumulating hypericins.}, journal = {The FEBS journal}, volume = {275}, number = {17}, pages = {4329-4342}, doi = {10.1111/j.1742-4658.2008.06576.x}, pmid = {18647343}, issn = {1742-464X}, mesh = {Anthracenes ; Base Sequence ; Chromatography, Liquid ; DNA Primers ; Escherichia coli/genetics ; Hypericum/*enzymology ; In Situ Hybridization ; Molecular Sequence Data ; Perylene/*analogs & derivatives/metabolism ; Phylogeny ; Polyketide Synthases/genetics/*isolation & purification/metabolism ; RNA Probes ; Recombinant Proteins/genetics/isolation & purification/metabolism ; Spectrometry, Mass, Electrospray Ionization ; }, abstract = {Hypericins are biologically active constituents of Hypericum perforatum (St John's wort). It is likely that emodin anthrone, an anthraquinone precursor of hypericins, is biosynthesized via the polyketide pathway by type III polyketide synthase (PKS). A PKS from H. perforatum, HpPKS2, was investigated for its possible involvement in the biosynthesis of hypericins. Phylogenetic tree analysis revealed that HpPKS2 groups with functionally divergent non-chalcone-producing plant-specific type III PKSs, but it is not particularly closely related to any of the currently known type III PKSs. A recombinant HpPKS2 expressed in Escherichia coli resulted in an enzyme of approximately 43 kDa. The purified enzyme catalysed the condensation of acetyl-CoA with two to seven malonyl-CoA to yield tri- to octaketide products, including octaketides SEK4 and SEK4b, as well as heptaketide aloesone. Although HpPKS2 was found to have octaketide synthase activity, production of emodin anthrone, a supposed octaketide precursor of hypericins, was not detected. The enzyme also accepted isobutyryl-CoA, benzoyl-CoA and hexanoyl-CoA as starter substrates producing a variety of tri- to heptaketide products. In situ RNA hybridization localized the HpPKS2 transcripts in H. perforatum leaf margins, flower petals and stamens, specifically in multicellular dark glands accumulating hypericins. Based on our results, HpPKS2 may have a role in the biosynthesis of hypericins in H. perforatum but some additional factors are possibly required for the production of emodin anthrone in vivo.}, } @article {pmid18645957, year = {2008}, author = {Abreu, FP and Silva, KT and Farina, M and Keim, CN and Lins, U}, title = {Greigite magnetosome membrane ultrastructure in 'Candidatus Magnetoglobus multicellularis'.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {11}, number = {2}, pages = {75-80}, pmid = {18645957}, issn = {1139-6709}, mesh = {Biomarkers ; Cell Membrane/*ultrastructure ; Deltaproteobacteria/*ultrastructure ; Histocytochemistry ; Inclusion Bodies/*ultrastructure ; *Iron ; Magnetics ; Microscopy, Electron, Transmission ; *Sulfides ; }, abstract = {The ultrastructure of the greigite magnetosome membrane in the multicellular magnetotactic bacteria 'Candidatus Magnetoglobus multicellularis' was studied. Each cell contains 80 membrane-enclosed iron-sulfide magnetosomes. Cytochemistry methods showed that the magnetosomes are enveloped by a structure whose staining pattern and dimensions are similar to those of the cytoplasmic membrane, indicating that the magnetosome membrane likely originates from the cytoplasmic membrane. Freeze-fracture showed intramembrane particles in the vesicles surrounding each magnetosome. Observations of cell membrane invaginations, the trilaminar membrane structure of immature magnetosomes, and empty vesicles together suggested that greigite magnetosome formation begins by invagination of the cell membrane, as has been proposed for magnetite magnetosomes.}, } @article {pmid18641265, year = {2008}, author = {Kanaoka, MM and Pillitteri, LJ and Fujii, H and Yoshida, Y and Bogenschutz, NL and Takabayashi, J and Zhu, JK and Torii, KU}, title = {SCREAM/ICE1 and SCREAM2 specify three cell-state transitional steps leading to arabidopsis stomatal differentiation.}, journal = {The Plant cell}, volume = {20}, number = {7}, pages = {1775-1785}, pmid = {18641265}, issn = {1040-4651}, support = {R01 GM059138/GM/NIGMS NIH HHS/United States ; R01GM059138/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/cytology/*metabolism ; Arabidopsis Proteins/genetics/metabolism/*physiology ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism/physiology ; Cell Differentiation/genetics/*physiology ; Helix-Loop-Helix Motifs/genetics ; Microscopy, Confocal ; Models, Biological ; Phylogeny ; Plant Epidermis/cytology/metabolism ; Plant Stomata/cytology/*metabolism ; Protein Binding ; Reverse Transcriptase Polymerase Chain Reaction ; Two-Hybrid System Techniques ; }, abstract = {Differentiation of specialized cell types in multicellular organisms requires orchestrated actions of cell fate determinants. Stomata, valves on the plant epidermis, are formed through a series of differentiation events mediated by three closely related basic-helix-loop-helix proteins: SPEECHLESS (SPCH), MUTE, and FAMA. However, it is not known what mechanism coordinates their actions. Here, we identify two paralogous proteins, SCREAM (SCRM) and SCRM2, which directly interact with and specify the sequential actions of SPCH, MUTE, and FAMA. The gain-of-function mutation in SCRM exhibited constitutive stomatal differentiation in the epidermis. Conversely, successive loss of SCRM and SCRM2 recapitulated the phenotypes of fama, mute, and spch, indicating that SCRM and SCRM2 together determined successive initiation, proliferation, and terminal differentiation of stomatal cell lineages. Our findings identify the core regulatory units of stomatal differentiation and suggest a model strikingly similar to cell-type differentiation in animals. Surprisingly, map-based cloning revealed that SCRM is INDUCER OF CBF EXPRESSION1, a master regulator of freezing tolerance, thus implicating a potential link between the transcriptional regulation of environmental adaptation and development in plants.}, } @article {pmid18634330, year = {2008}, author = {Perevozchikov, AP}, title = {[Sterols and their transport in animal development].}, journal = {Ontogenez}, volume = {39}, number = {3}, pages = {165-189}, pmid = {18634330}, issn = {0475-1450}, mesh = {Animals ; Cell Membrane/*metabolism ; Humans ; Signal Transduction/*physiology ; Sterols/*metabolism ; }, abstract = {The cellular content of different sterols in invertebrates and vertebrates as well as their origin (endogenous and food sources) and significance for the life cycle are comparatively reviewed. The initial signaling role of sterols in the vital activity (in all multicellular animals) and later obligatory incorporation of certain sterols in cell membranes as a plastic components (in vertebrates) are proposed based on the presented data.}, } @article {pmid18628961, year = {2008}, author = {Wang, X and Lavrov, DV}, title = {Seventeen new complete mtDNA sequences reveal extensive mitochondrial genome evolution within the Demospongiae.}, journal = {PloS one}, volume = {3}, number = {7}, pages = {e2723}, pmid = {18628961}, issn = {1932-6203}, mesh = {Animals ; DNA, Intergenic ; *DNA, Mitochondrial/chemistry ; Evolution, Molecular ; G1 Phase ; Genome ; Genome, Mitochondrial ; Introns ; Models, Genetic ; Nucleic Acid Conformation ; Nucleotides/chemistry ; Phylogeny ; Plakortis/metabolism ; Porifera ; RNA, Transfer/chemistry ; }, abstract = {Two major transitions in animal evolution--the origins of multicellularity and bilaterality--correlate with major changes in mitochondrial DNA (mtDNA) organization. Demosponges, the largest class in the phylum Porifera, underwent only the first of these transitions and their mitochondrial genomes display a peculiar combination of ancestral and animal-specific features. To get an insight into the evolution of mitochondrial genomes within the Demospongiae, we determined 17 new mtDNA sequences from this group and analyzing them with five previously published sequences. Our analysis revealed that all demosponge mtDNAs are 16- to 25-kbp circular molecules, containing 13-15 protein genes, 2 rRNA genes, and 2-27 tRNA genes. All but four pairs of sampled genomes had unique gene orders, with the number of shared gene boundaries ranging from 1 to 41. Although most demosponge species displayed low rates of mitochondrial sequence evolution, a significant acceleration in evolutionary rates occurred in the G1 group (orders Dendroceratida, Dictyoceratida, and Verticillitida). Large variation in mtDNA organization was also observed within the G0 group (order Homosclerophorida) including gene rearrangements, loss of tRNA genes, and the presence of two introns in Plakortis angulospiculatus. While introns are rare in modern-day demosponge mtDNA, we inferred that at least one intron was present in cox1 of the common ancestor of all demosponges. Our study uncovered an extensive mitochondrial genomic diversity within the Demospongiae. Although all sampled mitochondrial genomes retained some ancestral features, including a minimally modified genetic code, conserved structures of tRNA genes, and presence of multiple non-coding regions, they vary considerably in their size, gene content, gene order, and the rates of sequence evolution. Some of the changes in demosponge mtDNA, such as the loss of tRNA genes and the appearance of hairpin-containing repetitive elements, occurred in parallel in several lineages and suggest general trends in demosponge mtDNA evolution.}, } @article {pmid18626681, year = {2008}, author = {Aledo, JC}, title = {An early and anaerobic scenario for the transition to undifferentiated multicellularity.}, journal = {Journal of molecular evolution}, volume = {67}, number = {2}, pages = {145-153}, pmid = {18626681}, issn = {0022-2844}, mesh = {Anaerobiosis ; *Biological Evolution ; Cell Differentiation ; Glycolysis ; Models, Biological ; Thermodynamics ; }, abstract = {Glycolysis, an ancient energy-processing pathway, can operate either under an efficient but slow regime or, alternatively, under a dissipative but fast-working regime. Trading an increase in efficiency for a decrease in rate represents a cooperative behavior, while a dissipative metabolism can be regarded as a cheating strategy. Herein, using irreversible thermodynamic principles and methods derived from game theory, we investigate whether, and under what conditions, the interplay between these two metabolic strategies may have promoted the clustering of undifferentiated cells. In the current model, multicellularity implies the loss of motility, which represents a hindrance rather than a improvement when competing with mobile single-celled organisms. Despite that, when considering glycolysis as the only energy-processing pathway, we conclude that cells endowed with a low basal anabolic metabolism may have benefited from clustering when faced to compete with cells exhibiting a high anabolic activity. The current results suggest that the transition to multicellularity may have taken place much earlier than hitherto thought, providing support for an extended period of Precambrian metazoan diversification.}, } @article {pmid18621745, year = {2008}, author = {Kloepper, TH and Kienle, CN and Fasshauer, D}, title = {SNAREing the basis of multicellularity: consequences of protein family expansion during evolution.}, journal = {Molecular biology and evolution}, volume = {25}, number = {9}, pages = {2055-2068}, doi = {10.1093/molbev/msn151}, pmid = {18621745}, issn = {1537-1719}, mesh = {Animals ; Endosomes/metabolism ; Eukaryotic Cells/physiology ; *Evolution, Molecular ; Expressed Sequence Tags ; Fishes/genetics ; Gene Deletion ; Gene Duplication ; Genome ; Humans ; Invertebrates/genetics ; Phylogeny ; SNARE Proteins/classification/*genetics/physiology ; Vertebrates/genetics ; }, abstract = {Vesicle trafficking between intracellular compartments of eukaryotic cells is mediated by conserved protein machineries. In each trafficking step, fusion of the vesicle with the acceptor membrane is driven by a set of distinctive soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins that assemble into tight 4-helix bundle complexes between the fusing membranes. During evolution, about 20 primordial SNARE types were modified independently in different eukaryotic lineages by episodes of duplication and diversification. Here we show that 2 major changes in the SNARE repertoire occurred in the evolution of animals, each reflecting a main overhaul of the endomembrane system. In addition, we found several lineage-specific losses of distinct SNAREs, particularly in nematodes and platyhelminthes. The first major transformation took place during the transition to multicellularity. The primary event that occurred during this transformation was an increase in the numbers of endosomal SNAREs, but the SNARE-related factor lethal giant larvae also emerged. Apparently, enhanced endosomal sorting capabilities were an advantage for early multicellular animals. The second major transformation during the rise of vertebrates resulted in a robust expansion of the secretory set of SNAREs, which may have helped develop a more versatile secretory apparatus.}, } @article {pmid18621719, year = {2008}, author = {Manning, G and Young, SL and Miller, WT and Zhai, Y}, title = {The protist, Monosiga brevicollis, has a tyrosine kinase signaling network more elaborate and diverse than found in any known metazoan.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {28}, pages = {9674-9679}, pmid = {18621719}, issn = {1091-6490}, support = {R01 CA058530-14/CA/NCI NIH HHS/United States ; R01 HG004164/HG/NHGRI NIH HHS/United States ; R01 HG004164-01/HG/NHGRI NIH HHS/United States ; 1 R01 HG004164-01/HG/NHGRI NIH HHS/United States ; R01 CA058530/CA/NCI NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Eukaryota/*enzymology/genetics ; Evolution, Molecular ; Genome, Protozoan ; Genomics ; Phylogeny ; Protein-Tyrosine Kinases/*genetics ; *Signal Transduction ; }, abstract = {Tyrosine kinase signaling has long been considered a hallmark of intercellular communication, unique to multicellular animals. Our genomic analysis of the unicellular choanoflagellate Monosiga brevicollis discovers a remarkable count of 128 tyrosine kinases, 38 tyrosine phosphatases, and 123 phosphotyrosine (pTyr)-binding SH2 proteins, all higher counts than seen in any metazoan. This elaborate signaling network shows little orthology to metazoan counterparts yet displays many innovations reminiscent of metazoans. These include extracellular domains structurally related to those of metazoan receptor kinases, alternative methods for membrane anchoring and phosphotyrosine interaction in cytoplasmic kinases, and domain combinations that link kinases to small GTPase signaling and transcription. These proteins also display a wealth of combinations of known signaling domains. This uniquely divergent and elaborate signaling network illuminates the early evolution of pTyr signaling, explores innovative ways to traverse the cellular signaling circuitry, and shows extensive convergent evolution, highlighting pervasive constraints on pTyr signaling.}, } @article {pmid18616572, year = {2008}, author = {Stern, DL and Orgogozo, V}, title = {The loci of evolution: how predictable is genetic evolution?.}, journal = {Evolution; international journal of organic evolution}, volume = {62}, number = {9}, pages = {2155-2177}, pmid = {18616572}, issn = {0014-3820}, support = {R01 GM063622/GM/NIGMS NIH HHS/United States ; R01 GM063622-06A1/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Humans ; Phenotype ; *Regulatory Elements, Transcriptional ; }, abstract = {Is genetic evolution predictable? Evolutionary developmental biologists have argued that, at least for morphological traits, the answer is a resounding yes. Most mutations causing morphological variation are expected to reside in the cis-regulatory, rather than the coding, regions of developmental genes. This "cis-regulatory hypothesis" has recently come under attack. In this review, we first describe and critique the arguments that have been proposed in support of the cis-regulatory hypothesis. We then test the empirical support for the cis-regulatory hypothesis with a comprehensive survey of mutations responsible for phenotypic evolution in multicellular organisms. Cis-regulatory mutations currently represent approximately 22% of 331 identified genetic changes although the number of cis-regulatory changes published annually is rapidly increasing. Above the species level, cis-regulatory mutations altering morphology are more common than coding changes. Also, above the species level cis-regulatory mutations predominate for genes not involved in terminal differentiation. These patterns imply that the simple question "Do coding or cis-regulatory mutations cause more phenotypic evolution?" hides more interesting phenomena. Evolution in different kinds of populations and over different durations may result in selection of different kinds of mutations. Predicting the genetic basis of evolution requires a comprehensive synthesis of molecular developmental biology and population genetics.}, } @article {pmid18613816, year = {2008}, author = {Franklin-Tong, VE and Gourlay, CW}, title = {A role for actin in regulating apoptosis/programmed cell death: evidence spanning yeast, plants and animals.}, journal = {The Biochemical journal}, volume = {413}, number = {3}, pages = {389-404}, doi = {10.1042/BJ20080320}, pmid = {18613816}, issn = {1470-8728}, support = {G0600085/MRC_/Medical Research Council/United Kingdom ; 78573/MRC_/Medical Research Council/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Actins/genetics/metabolism/*physiology ; Animals ; Apoptosis/genetics/*physiology ; Mitochondria/metabolism ; Models, Biological ; Plants/genetics/*metabolism ; Reactive Oxygen Species/metabolism ; Yeasts/genetics/*metabolism ; }, abstract = {Achieving an understanding of how apoptosis/PCD (programmed cell death) is integrated within cellular responses to environmental and intracellular signals is a daunting task. From the sensation of a stimulus to the point of no return, a programme of cell death must engage specific pro-death components, whose effects can in turn be enhanced or repressed by downstream regulatory factors. In recent years, considerable progress has been made in our understanding of how components involved in these processes function. We now know that some of the factors involved in PCD networks have ancient origins that pre-date multicellularity and, indeed, eukaryotes themselves. A subject attracting much attention is the role that the actin cytoskeleton, itself a cellular component with ancient origins, plays in cell death regulation. Actin, a key cellular component, has an established role as a cellular sensor, with reorganization and alterations in actin dynamics being a well known consequence of signalling. A range of studies have revealed that actin also plays a key role in apoptosis/PCD regulation. Evidence implicating actin as a regulator of eukaryotic cell death has emerged from studies from the Animal, Plant and Fungal Kingdoms. Here we review recent data that provide evidence for an active, functional role for actin in determining whether PCD is triggered and executed, and discuss these findings within the context of regulation of actin dynamics.}, } @article {pmid18606206, year = {2008}, author = {Buck, M and Nehaniv, CL}, title = {Communication and complexity in a GRN-based multicellular system for graph colouring.}, journal = {Bio Systems}, volume = {94}, number = {1-2}, pages = {28-33}, doi = {10.1016/j.biosystems.2008.06.002}, pmid = {18606206}, issn = {1872-8324}, mesh = {*Algorithms ; *Artificial Intelligence ; Computational Biology/*methods ; *Computer Graphics ; *Gene Regulatory Networks ; *Models, Theoretical ; }, abstract = {Artificial Genetic Regulatory Networks (GRNs) are interesting control models through their simplicity and versatility. They can be easily implemented, evolved and modified, and their similarity to their biological counterparts makes them interesting for simulations of life-like systems as well. These aspects suggest they may be perfect control systems for distributed computing in diverse situations, but to be usable for such applications the computational power and evolvability of GRNs need to be studied. In this research we propose a simple distributed system implementing GRNs to solve the well known NP-complete graph colouring problem. Every node (cell) of the graph to be coloured is controlled by an instance of the same GRN. All the cells communicate directly with their immediate neighbours in the graph so as to set up a good colouring. The quality of this colouring directs the evolution of the GRNs using a genetic algorithm. We then observe the quality of the colouring for two different graphs according to different communication protocols and the number of different proteins in the cell (a measure for the possible complexity of a GRN). Those two points, being the main scalability issues that any computational paradigm raises, will then be discussed.}, } @article {pmid18602321, year = {2008}, author = {Chowdhury, I and Tharakan, B and Bhat, GK}, title = {Caspases - an update.}, journal = {Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology}, volume = {151}, number = {1}, pages = {10-27}, doi = {10.1016/j.cbpb.2008.05.010}, pmid = {18602321}, issn = {1096-4959}, mesh = {Animals ; Caspases/*chemistry/genetics/*metabolism ; Cell Physiological Phenomena ; Enzyme Activation ; Humans ; Phylogeny ; Protein Structure, Quaternary ; Signal Transduction ; }, abstract = {Caspases belong to a family of highly conserved aspartate-specific cysteine proteases and are members of the interleukin-1beta-converting enzyme family, present in multicellular organisms. The caspase gene family consists of 15 mammalian members that are grouped into two major sub-families, namely inflammatory caspases and apoptotic caspases. The apoptotic caspases are further subdivided into two sub-groups, initiator caspases and executioner caspases. The caspases form a caspase-cascade system that plays the central role in the induction, transduction and amplification of intracellular apoptotic signals for cell fate determination, regulation of immunity, and cellular proliferation and differentiation. The substrates of apoptotic caspases have been associated with cellular dismantling, while inflammatory caspases mediate the proteolytic activation of inflammatory cytokines. The activation of this delicate caspase-cascade system and its functions are regulated by a variety of regulatory molecules, such as the inhibitor of apoptosis protein (IAP), FLICE, calpain, and Ca(2+). Based on the available literature we have reviewed and discussed the members of the caspase family, caspase-cascade system, caspase-regulating molecules and their apoptotic and non-apoptotic functions in cellular life and death. Also recent progress in the molecular structure and physiological role of non-mammalian caspases such as paracaspases, metacaspases and caspase-like-protease family members are included in relation to that of mammalian species.}, } @article {pmid18599681, year = {2008}, author = {Elhai, J and Kato, M and Cousins, S and Lindblad, P and Costa, JL}, title = {Very small mobile repeated elements in cyanobacterial genomes.}, journal = {Genome research}, volume = {18}, number = {9}, pages = {1484-1499}, pmid = {18599681}, issn = {1088-9051}, mesh = {Bacterial Proteins/genetics ; Base Sequence ; Cyanobacteria/*genetics ; *Genome, Bacterial ; Interspersed Repetitive Sequences/*genetics ; Models, Biological ; Molecular Sequence Data ; Mutation ; Nested Genes ; Nucleic Acid Conformation ; Phylogeny ; }, abstract = {Mobile DNA elements play a major role in genome plasticity and other evolutionary processes, an insight gained primarily through the study of transposons and retrotransposons (generally approximately 1000 nt or longer). These elements spawn smaller parasitic versions (generally >100 nt) that propagate through proteins encoded by the full elements. Highly repeated sequences smaller than 100 nt have been described, but they are either nonmobile or their origins are not known. We have surveyed the genome of the multicellular cyanobacterium, Nostoc punctiforme, and its relatives for small dispersed repeat (SDR) sequences and have identified eight families in the range of from 21 to 27 nucleotides. Three of the families (SDR4, SDR5, and SDR6), despite little sequence similarity, share a common predicted secondary structure, a conclusion supported by patterns of compensatory mutations. The SDR elements are found in a diverse set of contexts, often embedded within tandemly repeated heptameric sequences or within minitransposons. One element (SDR5) is found exclusively within instances of an octamer, HIP1, that is highly over-represented in the genomes of many cyanobacteria. Two elements (SDR1 and SDR4) often are found within copies of themselves, producing complex nested insertions. An analysis of SDR elements within cyanobacterial genomes indicate that they are essentially confined to a coherent subgroup. The evidence indicates that some of the SDR elements, probably working through RNA intermediates, have been mobile in recent evolutionary time, making them perhaps the smallest known mobile elements.}, } @article {pmid18599463, year = {2008}, author = {Pincus, D and Letunic, I and Bork, P and Lim, WA}, title = {Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {28}, pages = {9680-9684}, pmid = {18599463}, issn = {1091-6490}, mesh = {Animals ; Eukaryota/genetics ; *Evolution, Molecular ; Genome/genetics ; Phylogeny ; Protein Tyrosine Phosphatases/*genetics ; Protein-Tyrosine Kinases/*genetics ; Signal Transduction/*genetics ; src Homology Domains ; }, abstract = {Multicellular animals use a three-part molecular toolkit to mediate phospho-tyrosine signaling: Tyrosine kinases (TyrK), protein tyrosine phosphatases (PTP), and Src Homology 2 (SH2) domains function, respectively, as "writers," "erasers," and "readers" of phospho-tyrosine modifications. How did this system of three components evolve, given their interdependent function? Here, we examine the usage of these components in 41 eukaryotic genomes, including the newly sequenced genome of the choanoflagellate, Monosiga brevicollis, the closest known unicellular relative to metazoans. This analysis indicates that SH2 and PTP domains likely evolved earliest-a handful of these domains are found in premetazoan eukaryotes lacking tyrosine kinases, most likely to deal with limited tyrosine phosphorylation cross-catalyzed by promiscuous Ser/Thr kinases. Modern TyrK proteins, however, are only observed in two lineages, metazoans and choanoflagellates. These two lineages show a dramatic coexpansion of all three domain families. Concurrent expansion of the three domain families is consistent with a stepwise evolutionary model in which preexisting SH2 and PTP domains were of limited utility until the appearance of the TyrK domain in the last common ancestor of metazoans and choanoflagellates. The emergence of the full three-component signaling system, with its dramatically increased encoding potential, may have contributed to the advent of metazoan multicellularity.}, } @article {pmid18593478, year = {2008}, author = {Veerappan, CS and Avramova, Z and Moriyama, EN}, title = {Evolution of SET-domain protein families in the unicellular and multicellular Ascomycota fungi.}, journal = {BMC evolutionary biology}, volume = {8}, number = {}, pages = {190}, pmid = {18593478}, issn = {1471-2148}, mesh = {Animals ; Ascomycota/*genetics ; Conserved Sequence ; *Evolution, Molecular ; Genes, Fungal/*genetics ; Genome, Fungal ; Methyltransferases/genetics ; Multigene Family/*genetics ; Phylogeny ; Protein Structure, Tertiary ; }, abstract = {BACKGROUND: The evolution of multicellularity is accompanied by the occurrence of differentiated tissues, of organismal developmental programs, and of mechanisms keeping the balance between proliferation and differentiation. Initially, the SET-domain proteins were associated exclusively with regulation of developmental genes in metazoa. However, finding of SET-domain genes in the unicellular yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe suggested that SET-domain proteins regulate a much broader variety of biological programs. Intuitively, it is expected that the numbers, types, and biochemical specificity of SET-domain proteins of multicellular versus unicellular forms would reflect the differences in their biology. However, comparisons across the unicellular and multicellular domains of life are complicated by the lack of knowledge of the ancestral SET-domain genes. Even within the crown group, different biological systems might use the epigenetic 'code' differently, adapting it to organism-specific needs. Simplifying the model, we undertook a systematic phylogenetic analysis of one monophyletic fungal group (Ascomycetes) containing unicellular yeasts, Saccharomycotina (hemiascomycetes), and a filamentous fungal group, Pezizomycotina (euascomycetes).

RESULTS: Systematic analysis of the SET-domain genes across an entire eukaryotic phylum has outlined clear distinctions in the SET-domain gene collections in the unicellular and in the multicellular (filamentous) relatives; diversification of SET-domain gene families has increased further with the expansion and elaboration of multicellularity in animal and plant systems. We found several ascomycota-specific SET-domain gene groups; each was unique to either Saccharomycotina or Pezizomycotina fungi. Our analysis revealed that the numbers and types of SET-domain genes in the Saccharomycotina did not reflect the habitats, pathogenicity, mechanisms of sexuality, or the ability to undergo morphogenic transformations. However, novel genes have appeared for functions associated with the transition to multicellularity. Descendents of most of the SET-domain gene families found in the filamentous fungi could be traced in the genomes of extant animals and plants, albeit as more complex structural forms.

CONCLUSION: SET-domain genes found in the filamentous species but absent from the unicellular sister group reflect two alternative evolutionary events: deletion from the yeast genomes or appearance of novel structures in filamentous fungal groups. There were no Ascomycota-specific SET-domain gene families (i.e., absent from animal and plant genomes); however, plants and animals share SET-domain gene subfamilies that do not exist in the fungi. Phylogenetic and gene-structure analyses defined several animal and plant SET-domain genes as sister groups while those of fungal origin were basal to them. Plants and animals also share SET-domain subfamilies that do not exist in fungi.}, } @article {pmid18556646, year = {2008}, author = {Seeman, E}, title = {Structural basis of growth-related gain and age-related loss of bone strength.}, journal = {Rheumatology (Oxford, England)}, volume = {47 Suppl 4}, number = {Suppl 4}, pages = {iv2-8}, pmid = {18556646}, issn = {1462-0332}, mesh = {Adolescent ; Adult ; Aged ; *Bone Density ; Bone Development/*physiology ; Bone Remodeling/physiology ; Bone and Bones/*physiopathology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Middle Aged ; Osteoporosis/*physiopathology ; Sex Factors ; }, abstract = {If bone strength was the only requirement of skeleton, it could be achieved with bulk, but bone must also be light. During growth, bone modelling and remodelling optimize strength, by depositing bone where it is needed, and minimize mass, by removing it from where it is not. The population variance in bone traits is established before puberty and the position of an individual's bone size and mass tracks in the percentile of origin. Larger cross-sections have a comparably larger marrow cavity, which results in a lower volumetric BMD (vBMD), thereby avoiding bulk. Excavation of a marrow cavity thus minimizes mass and shifts the cortex radially, increasing rigidity. Smaller cross-sections are assembled by excavating a smaller marrow cavity leaving a relatively thicker cortex producing a higher vBMD, avoiding the fragility of slenderness. Variation in cellular activity around the periosteal and endocortical envelopes fashions the diverse shapes of adjacent cross-sections. Advancing age is associated with a decline in periosteal bone formation, a decline in the volume of bone formed by each basic multicellular unit (BMU), continued resorption by each BMU, and high remodelling after menopause. Bone loss in young adulthood has modest structural and biomechanical consequences because the negative BMU balance is driven by reduced bone formation, remodelling is slow and periosteal apposition continues shifting the thinned cortex radially. But after the menopause, increased remodelling, worsening negative BMU balance and a decline in periosteal apposition accelerate cortical thinning and porosity, trabecular thinning and loss of connectivity. Interstitial bone, unexposed to surface remodelling becomes more densely mineralized, has few osteocytes and greater collagen cross-linking, and accumulates microdamage. These changes produce the material and structural abnormalities responsible for bone fragility.}, } @article {pmid18588686, year = {2008}, author = {Fox, AK and Tuch, BB and Chuang, JH}, title = {Measuring the prevalence of regional mutation rates: an analysis of silent substitutions in mammals, fungi, and insects.}, journal = {BMC evolutionary biology}, volume = {8}, number = {}, pages = {186}, pmid = {18588686}, issn = {1471-2148}, mesh = {Amino Acid Substitution/*genetics ; Animals ; Fungi/*genetics ; Insecta/*genetics ; Mammals/*genetics ; *Mutation ; Phylogeny ; Selection, Genetic ; }, abstract = {BACKGROUND: The patterns of mutation vary both within and across genomes. It has been shown for a few mammals that mutation rates vary within the genome, while for unknown reasons, the sensu stricto yeasts have uniform rates instead. The generality of these observations has been unknown. Here we examine silent site substitutions in a more expansive set (20 mammals, 27 fungi, 4 insects) to determine why some genomes demonstrate this mosaic distribution and why others are uniform.

RESULTS: We applied several intragene and intergene correlation tests to measure regional substitution patterns. Assuming that silent sites are a reasonable approximation to neutrally mutating sequence, our results show that all multicellular eukaryotes exhibit mutational heterogeneity. In striking contrast, all fungi are mutationally uniform - with the exception of three Candida species: C. albicans, C. dubliniensis, and C. tropicalis. We speculate that aspects of replication timing may be responsible for distinguishing these species. Our analysis also reveals classes of genes whose silent sites behave anomalously with respect to the mutational background in many species, indicating prevalent selective pressures. Genes associated with nucleotide binding or gene regulation have consistently low silent substitution rates in every mammalian species, as well as multiple fungi. On the other hand, receptor genes repeatedly exhibit high silent substitution rates, suggesting they have been influenced by diversifying selection.

CONCLUSION: Our findings provide a framework for understanding the regional mutational properties of eukaryotes, revealing a sharp difference between fungi and multicellular species. They also elucidate common selective pressures acting on eukaryotic silent sites, with frequent evidence for both purifying and diversifying selection.}, } @article {pmid18580166, year = {2008}, author = {Lindahl, SG}, title = {Oxygen and life on earth: an anesthesiologist's views on oxygen evolution, discovery, sensing, and utilization.}, journal = {Anesthesiology}, volume = {109}, number = {1}, pages = {7-13}, doi = {10.1097/ALN.0b013e31817b5a7e}, pmid = {18580166}, issn = {1528-1175}, mesh = {*Anesthesiology ; Animals ; Atmosphere/analysis/chemistry ; *Earth, Planet ; *Evolution, Chemical ; Humans ; *Life ; Oxygen/*chemistry/isolation & purification/*metabolism ; Photochemistry ; *Physicians ; }, abstract = {The advent of oxygenic photosynthesis and the accumulation of oxygen in our atmosphere opened up new possibilities for the development of life on Earth. The availability of oxygen, the most capable electron acceptor on our planet, allowed the development of highly efficient energy production from oxidative phosphorylation, which shaped the evolutionary development of aerobic life forms from the first multicellular organisms to the vertebrates.}, } @article {pmid18574100, year = {2008}, author = {Magie, CR and Martindale, MQ}, title = {Cell-cell adhesion in the cnidaria: insights into the evolution of tissue morphogenesis.}, journal = {The Biological bulletin}, volume = {214}, number = {3}, pages = {218-232}, doi = {10.2307/25470665}, pmid = {18574100}, issn = {0006-3185}, mesh = {Animals ; *Cell Adhesion ; Cnidaria/genetics/*physiology ; *Evolution, Molecular ; *Morphogenesis ; }, abstract = {Cell adhesion is a major aspect of cell biology and one of the fundamental processes involved in the development of a multicellular animal. Adhesive mechanisms, both cell-cell and between cell and extracellular matrix, are intimately involved in assembling cells into the three-dimensional structures of tissues and organs. The modulation of adhesive complexes could therefore be seen as a central component in the molecular control of morphogenesis, translating information encoded within the genome into organismal form. The availability of whole genomes from early-branching metazoa such as cnidarians is providing important insights into the evolution of adhesive processes by allowing for the easy identification of the genes involved in adhesion in these organisms. Discovery of the molecular nature of cell adhesion in the early-branching groups, coupled with comparisons across the metazoa, is revealing the ways evolution has tinkered with this vital cellular process in the generation of the myriad forms seen across the animal kingdom.}, } @article {pmid18559822, year = {2008}, author = {Schlichting, CD}, title = {Hidden reaction norms, cryptic genetic variation, and evolvability.}, journal = {Annals of the New York Academy of Sciences}, volume = {1133}, number = {}, pages = {187-203}, doi = {10.1196/annals.1438.010}, pmid = {18559822}, issn = {0077-8923}, mesh = {Adaptation, Biological/physiology ; Animals ; *Evolution, Molecular ; *Genetic Drift ; Genetic Variation/*physiology ; Humans ; *Models, Genetic ; *Selection, Genetic ; }, abstract = {There is reason to suspect that hidden reaction norms (variation that is phenotypically expressed only after changes in internal or external environmental conditions) may store an evolutionarily significant pool of cryptic genetic variation upon which selection may act. I review mechanisms that may hide variation and the processes that can release this variation. I discuss the potential significance of cryptic genetic variation and elaborate on an example where the release of such variation initiated the evolution of the genetic architecture of multicellular organisms.}, } @article {pmid18546335, year = {2008}, author = {Kurosaka, S and Kashina, A}, title = {Cell biology of embryonic migration.}, journal = {Birth defects research. Part C, Embryo today : reviews}, volume = {84}, number = {2}, pages = {102-122}, pmid = {18546335}, issn = {1542-9768}, support = {R01 HL084419/HL/NHLBI NIH HHS/United States ; R01 HL084419-01A1/HL/NHLBI NIH HHS/United States ; 5R01HL084419-01 A1/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Brain/embryology ; Cell Adhesion/physiology ; Cell Movement/*physiology ; Cytoskeleton/physiology ; Embryo, Mammalian/*physiology ; Embryo, Nonmammalian/*physiology ; Embryonic Development/*physiology ; Germ Cells/physiology ; Heart/embryology ; Humans ; Mesoderm/cytology/physiology ; Models, Biological ; Movement ; Neural Crest/physiology ; Protein Processing, Post-Translational ; }, abstract = {Cell migration is an evolutionarily conserved mechanism that underlies the development and functioning of uni- and multicellular organisms and takes place in normal and pathogenic processes, including various events of embryogenesis, wound healing, immune response, cancer metastases, and angiogenesis. Despite the differences in the cell types that take part in different migratory events, it is believed that all of these migrations occur by similar molecular mechanisms, whose major components have been functionally conserved in evolution and whose perturbation leads to severe developmental defects. These mechanisms involve intricate cytoskeleton-based molecular machines that can sense the environment, respond to signals, and modulate the entire cell behavior. A big question that has concerned the researchers for decades relates to the coordination of cell migration in situ and its relation to the intracellular aspects of the cell migratory mechanisms. Traditionally, this question has been addressed by researchers that considered the intra- and extracellular mechanisms driving migration in separate sets of studies. As more data accumulate researchers are now able to integrate all of the available information and consider the intracellular mechanisms of cell migration in the context of the developing organisms that contain additional levels of complexity provided by extracellular regulation. This review provides a broad summary of the existing and emerging data in the cell and developmental biology fields regarding cell migration during development.}, } @article {pmid18541214, year = {2008}, author = {Gottwein, E and Cullen, BR}, title = {Viral and cellular microRNAs as determinants of viral pathogenesis and immunity.}, journal = {Cell host & microbe}, volume = {3}, number = {6}, pages = {375-387}, pmid = {18541214}, issn = {1934-6069}, support = {R56 AI067968/AI/NIAID NIH HHS/United States ; GM071408/GM/NIGMS NIH HHS/United States ; R01 AI067968/AI/NIAID NIH HHS/United States ; AI067968/AI/NIAID NIH HHS/United States ; R01 GM071408/GM/NIGMS NIH HHS/United States ; R01 GM071408-04/GM/NIGMS NIH HHS/United States ; R01 GM071408-03/GM/NIGMS NIH HHS/United States ; R01 AI067968-04/AI/NIAID NIH HHS/United States ; R01 AI067968-03/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Evolution, Molecular ; Gene Expression/drug effects ; Gene Expression Regulation, Viral/drug effects ; *Host-Pathogen Interactions ; Humans ; MicroRNAs/*genetics/metabolism/pharmacology ; RNA, Viral/genetics/metabolism ; Sequence Alignment ; Virus Diseases/genetics/*immunology ; *Virus Physiological Phenomena ; Viruses/genetics/immunology/*pathogenicity ; }, abstract = {MicroRNAs (miRNAs) have recently emerged as key posttranscriptional regulators of gene expression in multicellular eukaryotes. It is increasingly clear that miRNAs of both viral and cellular origin can positively or negatively influence viral replication. Viral miRNAs can directly alter host physiology, including components of the immune system, and host miRNAs can directly alter the virus life cycle. Here, we discuss what is known about how viral and cellular miRNAs influence viral replication and pathogenic potential through their regulation of viral mRNAs or by reshaping cellular gene expression.}, } @article {pmid18535014, year = {2008}, author = {Zhao, Y and Epstein, RJ}, title = {Programmed genetic instability: a tumor-permissive mechanism for maintaining the evolvability of higher species through methylation-dependent mutation of DNA repair genes in the male germ line.}, journal = {Molecular biology and evolution}, volume = {25}, number = {8}, pages = {1737-1749}, pmid = {18535014}, issn = {1537-1719}, mesh = {Animals ; Computational Biology ; *DNA Methylation ; DNA Repair/*genetics ; *Evolution, Molecular ; *Genes, Tumor Suppressor ; Genomic Instability/*genetics ; Humans ; Male ; Mice ; Mutation/genetics ; Neoplasms/*genetics ; *Phylogeny ; Principal Component Analysis ; Species Specificity ; }, abstract = {Tumor suppressor genes are classified by their somatic behavior either as caretakers (CTs) that maintain DNA integrity or as gatekeepers (GKs) that regulate cell survival, but the germ line role of these disease-related gene subgroups may differ. To test this hypothesis, we have used genomic data mining to compare the features of human CTs (n = 38), GKs (n = 36), DNA repair genes (n = 165), apoptosis genes (n = 622), and their orthologs. This analysis reveals that repair genes are numerically less common than apoptosis genes in the genomes of multicellular organisms (P < 0.01), whereas CT orthologs are commoner than GK orthologs in unicellular organisms (P < 0.05). Gene targeting data show that CTs are less essential than GKs for survival of multicellular organisms (P < 0.0005) and that CT knockouts often permit offspring viability at the cost of male sterility. Patterns of human familial oncogenic mutations confirm that isolated CT loss is commoner than is isolated GK loss (P < 0.00001). In sexually reproducing species, CTs appear subject to less efficient purifying selection (i.e., higher Ka/Ks) than GKs (P = 0.000003); the faster evolution of CTs seems likely to be mediated by gene methylation and reduced transcription-coupled repair, based on differences in dinucleotide patterns (P = 0.001). These data suggest that germ line CT/repair gene function is relatively dispensable for survival, and imply that milder (e.g., epimutational) male prezygotic repair defects could enhance sperm variation-and hence environmental adaptation and speciation-while sparing fertility. We submit that CTs and repair genes are general targets for epigenetically initiated adaptive evolution, and propose a model in which human cancers arise in part as an evolutionarily programmed side effect of age- and damage-inducible genetic instability affecting both somatic and germ line lineages.}, } @article {pmid18517658, year = {2008}, author = {Morishita, Y and Iwasa, Y}, title = {Optimal placement of multiple morphogen sources.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {77}, number = {4 Pt 1}, pages = {041909}, doi = {10.1103/PhysRevE.77.041909}, pmid = {18517658}, issn = {1539-3755}, mesh = {Animals ; Body Patterning/physiology ; Ectoderm/*metabolism ; Embryonic Induction ; Entropy ; Limb Buds/*embryology ; Mesoderm/*metabolism ; *Models, Biological ; Morphogenesis/physiology ; Signal Transduction/genetics ; Vertebrates/*embryology/genetics/metabolism ; }, abstract = {During development, cells grow, differentiate, divide, and die according to their spatial positions, yet the positional information given to cells by morphogens (diffusive chemicals) includes considerable noises from various origins. In this paper, we examine a relationship between fluctuations in morphogen concentrations that the cells receive and the precision of positional specification by the morphogens in multidimensional space. As a method to quantify the precision, we introduce a measure of "ambiguity of positional information," based on the information entropy. We discover that the location of morphogen sources crucially affects the ambiguity, and that the ambiguity becomes minimum when the angle made by gradient vectors of different morphogens cross at a right angle in a target region under a given organ geometry (orthogonality principle). We conjecture that morphogen sources in development might be placed at the nearly optimal position that minimizes the ambiguity of positional information. This is supported by experimental data on the configurations of two major sources of spatial patterning, the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA), in vertebrate limb development. Indeed, their predicted configuration agrees very well with the one observed in experiments. We believe that the placement of morphogen sources to minimize the ambiguity of positional information is a basic principle in development of multicellular organisms beyond this particular example.}, } @article {pmid18516494, year = {2008}, author = {Guth, SI and Wegner, M}, title = {Having it both ways: Sox protein function between conservation and innovation.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {65}, number = {19}, pages = {3000-3018}, doi = {10.1007/s00018-008-8138-7}, pmid = {18516494}, issn = {1420-682X}, mesh = {Animals ; Bone and Bones/embryology/physiology ; Central Nervous System/embryology/growth & development/physiology ; Embryonic Development/physiology ; Gonads/embryology/growth & development/physiology ; Humans ; Multigene Family ; Phylogeny ; Transcription Factors/classification/genetics/*metabolism ; }, abstract = {Transcription factors of the Sox family arose around the advent of multicellularity in animals, arguing that their ability to regulate the expression of extracellular matrix, cell adhesion and signaling molecules may have been instrumental in the generation of metazoans. In particular, during vertebrate evolution, the Sox family experienced a phase of expansion that led to the appearance of groups of highly homologous Sox proteins and the division of existing Sox protein functions among group members. It furthermore allowed Sox transcription factors to acquire numerous novel functions. These past events of subfunctionalization and neofunctionalization can still be recognized today in all groups of the Sox family. They have led to partial functional redundancies, but also to interesting species-specific variations in the developmental roles of Sox proteins as shown here for the SoxB and the SoxE groups.}, } @article {pmid18511852, year = {2008}, author = {Cooper, EL}, title = {From Darwin and Metchnikoff to Burnet and beyond.}, journal = {Contributions to microbiology}, volume = {15}, number = {}, pages = {1-11}, doi = {10.1159/000135680}, pmid = {18511852}, issn = {1420-9519}, mesh = {Animals ; Biological Evolution ; Cnidaria/genetics/*immunology/physiology ; Eukaryota/genetics/*immunology/physiology ; Immunity, Innate ; *Phagocytosis ; Porifera/genetics/*immunology/physiology ; Signal Transduction ; Toll-Like Receptors/genetics/immunology ; }, abstract = {Phagocytosis in unicellular animals represents the most ancient and ubiquitous form of defense against foreign material. Unicellular invertebrates can phagocytose for food and defense. Multicellular invertebrates and vertebrates possess phagocytic cells and have evolved more complex functions attributed to immunodefense cells that specialized into cellular and humoral immune responses. Thus all animals possess: innate, natural, nonspecific (no memory) nonanticipatory, nonclonal, germline (hard wired) host defense functions. In addition, all vertebrates possess: adaptive, induced, specific (memory), anticipatory, clonal, somatic (flexible) immune responses. A similar situation exists with respect to components of the signaling system, immunity and development. With multicellularity, clearly numerous immune response characteristics are not possible in unicellular forms or even those that straddle the divide between unicellularity and multicellularity, beginning with colonial/social protozoans. Still, it is instructive to elucidate a hierarchy of animals based upon immunologic characteristics and how they parallel other physiological traits. Evidence is presented that the most primitive of invertebrates prior to the evolution of multicellular organisms possess varying degrees of complexity at the molecular level of those hallmarks that now characterize the immune system.}, } @article {pmid18510927, year = {2008}, author = {Lee, JH and Lin, H and Joo, S and Goodenough, U}, title = {Early sexual origins of homeoprotein heterodimerization and evolution of the plant KNOX/BELL family.}, journal = {Cell}, volume = {133}, number = {5}, pages = {829-840}, doi = {10.1016/j.cell.2008.04.028}, pmid = {18510927}, issn = {1097-4172}, mesh = {Algal Proteins/*genetics ; Amino Acid Sequence ; Animals ; Chlamydomonas reinhardtii/*genetics/physiology ; Dimerization ; Diploidy ; *Evolution, Molecular ; Gene Expression Regulation ; Haploidy ; Homeodomain Proteins/*genetics ; Molecular Sequence Data ; Plant Proteins/*genetics ; Plants ; Sequence Alignment ; Two-Hybrid System Techniques ; }, abstract = {Developmental mechanisms that yield multicellular diversity are proving to be well conserved within lineages, generating interest in their origins in unicellular ancestors. We report that molecular regulation of the haploid-diploid transition in Chlamydomonas, a unicellular green soil alga, shares common ancestry with differentiation pathways in land plants. Two homeoproteins, Gsp1 and Gsm1, contributed by gametes of plus and minus mating types respectively, physically interact and translocate from the cytosol to the nucleus upon gametic fusion, initiating zygote development. Their ectopic expression activates zygote development in vegetative cells and, in a diploid background, the resulting zygotes undergo a normal meiosis. Gsm1/Gsp1 dyads share sequence homology with and are functionally related to KNOX/BELL dyads regulating stem-cell (meristem) specification in land plants. We propose that combinatorial homeoprotein-based transcriptional control, a core feature of the fungal/animal radiation, may have originated in a sexual context and enabled the evolution of land-plant body plans.}, } @article {pmid18509435, year = {2008}, author = {Reece, SE and Drew, DR and Gardner, A}, title = {Sex ratio adjustment and kin discrimination in malaria parasites.}, journal = {Nature}, volume = {453}, number = {7195}, pages = {609-614}, pmid = {18509435}, issn = {1476-4687}, support = {/WT_/Wellcome Trust/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Cues ; Female ; Fertility/genetics/physiology ; Genetic Variation ; Genotype ; Humans ; Malaria/*parasitology ; Male ; Models, Biological ; Plasmodium chabaudi/genetics/*physiology ; *Sex Ratio ; }, abstract = {Malaria parasites and related Apicomplexans are the causative agents of the some of the most serious infectious diseases of humans, companion animals, livestock and wildlife. These parasites must undergo sexual reproduction to transmit from vertebrate hosts to vectors, and their sex ratios are consistently female-biased. Sex allocation theory, a cornerstone of evolutionary biology, is remarkably successful at explaining female-biased sex ratios in multicellular taxa, but has proved controversial when applied to malaria parasites. Here we show that, as predicted by theory, sex ratio is an important fitness-determining trait and Plasmodium chabaudi parasites adjust their sex allocation in response to the presence of unrelated conspecifics. This suggests that P. chabaudi parasites use kin discrimination to evaluate the genetic diversity of their infections, and they adjust their behaviour in response to environmental cues. Malaria parasites provide a novel way to test evolutionary theory, and support the generality and power of a darwinian approach.}, } @article {pmid18507740, year = {2008}, author = {Johnson, LJ}, title = {Selfish genetic elements favor the evolution of a distinction between soma and germline.}, journal = {Evolution; international journal of organic evolution}, volume = {62}, number = {8}, pages = {2122-2124}, doi = {10.1111/j.1558-5646.2008.00433.x}, pmid = {18507740}, issn = {0014-3820}, mesh = {Algorithms ; Animals ; *Biological Evolution ; DNA Transposable Elements/genetics ; Female ; Genes ; Genetics ; Genomics ; Male ; *Models, Genetic ; Models, Theoretical ; Phylogeny ; Selection, Genetic ; Symbiosis ; }, abstract = {Many multicellular organisms have evolved a dedicated germline. This can benefit the whole organism, but its advantages to genetic parasites have not been explored. Here I model the evolutionary success of a selfish element, such as a transposable element or endosymbiont, which is capable of creating or strengthening a germline-soma distinction in a primitively multicellular host, and find that it will always benefit the element to do so. Genes causing germline sequestration can therefore spread in a population even if germline sequestration is maladaptive for the host organism. Costly selfish elements are expected to survive only in sexual populations, so sexual species may experience an additional push toward germline-soma distinction, and hence toward cell differentiation and multicellularity.}, } @article {pmid18493051, year = {2008}, author = {Wheeler, GL and Miranda-Saavedra, D and Barton, GJ}, title = {Genome analysis of the unicellular green alga Chlamydomonas reinhardtii Indicates an ancient evolutionary origin for key pattern recognition and cell-signaling protein families.}, journal = {Genetics}, volume = {179}, number = {1}, pages = {193-197}, pmid = {18493051}, issn = {0016-6731}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Algal Proteins/*genetics ; Amino Acid Sequence ; Animals ; Chlamydomonas reinhardtii/*genetics ; Conserved Sequence/genetics ; *Evolution, Molecular ; Genomics ; Molecular Sequence Data ; Multigene Family/*genetics ; *Protein Structure, Tertiary ; Protein-Tyrosine Kinases/genetics ; Signal Transduction/*genetics ; Species Specificity ; }, abstract = {The evolution of specific cell signaling and adhesion domains may have played an important role in the transition to a multicellular existence in the metazoans. Genomic analysis indicates that several signaling domains predominately found in animals are also present in the unicellular green alga, Chlamydomonas reinhardtii. A large group of proteins is present, containing scavenger receptor cysteine-rich (SRCR) and C-type lectin domains, which function in ligand binding and play key roles in the innate immune system of animals. Chlamydomonas also contains a large family of putative tyrosine kinases, suggesting an important role for phosphotyrosine signaling in the green algae. These important signaling domains may therefore be widespread among eukaryotes and most probably evolved in ancestral eukaryotes before the divergence of the Opisthokonts (the animal and fungal lineage).}, } @article {pmid18493041, year = {2008}, author = {Casas-Mollano, JA and Rohr, J and Kim, EJ and Balassa, E and van Dijk, K and Cerutti, H}, title = {Diversification of the core RNA interference machinery in Chlamydomonas reinhardtii and the role of DCL1 in transposon silencing.}, journal = {Genetics}, volume = {179}, number = {1}, pages = {69-81}, pmid = {18493041}, issn = {0016-6731}, mesh = {Animals ; Base Sequence ; Chlamydomonas reinhardtii/*enzymology/genetics ; Chromatin Immunoprecipitation ; Cluster Analysis ; DNA Primers/genetics ; DNA Transposable Elements/*genetics ; Endoribonucleases/*genetics ; *Genetic Variation ; Immunoblotting ; Molecular Sequence Data ; *Phylogeny ; *RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonuclease III/*genetics ; Sequence Analysis, DNA ; }, abstract = {Small RNA-guided gene silencing is an evolutionarily conserved process that operates by a variety of molecular mechanisms. In multicellular eukaryotes, the core components of RNA-mediated silencing have significantly expanded and diversified, resulting in partly distinct pathways for the epigenetic control of gene expression and genomic parasites. In contrast, many unicellular organisms with small nuclear genomes seem to have lost entirely the RNA-silencing machinery or have retained only a basic set of components. We report here that Chlamydomonas reinhardtii, a unicellular eukaryote with a relatively large nuclear genome, has undergone extensive duplication of Dicer and Argonaute polypeptides after the divergence of the green algae and land plant lineages. Chlamydomonas encodes three Dicers and three Argonautes with DICER-LIKE1 (DCL1) and ARGONAUTE1 being more divergent than the other paralogs. Interestingly, DCL1 is uniquely involved in the post-transcriptional silencing of retrotransposons such as TOC1. Moreover, on the basis of the subcellular distribution of TOC1 small RNAs and target transcripts, this pathway most likely operates in the nucleus. However, Chlamydomonas also relies on a DCL1-independent, transcriptional silencing mechanism(s) for the maintenance of transposon repression. Our results suggest that multiple, partly redundant epigenetic processes are involved in preventing transposon mobilization in this green alga.}, } @article {pmid18493038, year = {2008}, author = {Riaño-Pachón, DM and Corrêa, LG and Trejos-Espinosa, R and Mueller-Roeber, B}, title = {Green transcription factors: a chlamydomonas overview.}, journal = {Genetics}, volume = {179}, number = {1}, pages = {31-39}, pmid = {18493038}, issn = {0016-6731}, mesh = {Animals ; Chlamydomonas reinhardtii/*genetics ; Computational Biology ; Genes, Protozoan/*genetics ; Genomics ; Magnoliopsida/*genetics ; *Phylogeny ; Species Specificity ; Transcription Factors/*genetics ; }, abstract = {Transcription factors (TFs) control gene expression by interacting with cis-elements in target gene promoters. Transcription regulators (TRs) assist in controlling gene expression through interaction with TFs, chromatin remodeling, or other mechanisms. Both types of proteins thus constitute master controllers of dynamic transcriptional networks. To uncover such control elements in the photosynthetic green alga Chlamydomonas reinhardtii, we performed a comprehensive analysis of its genome sequence. In total, we identified 234 genes encoding 147 TFs and 87 TRs of approximately 40 families. The set of putative TFs and TRs, including their transcript and protein sequences, domain architectures, and supporting information about putative orthologs, is available at http://plntfdb.bio.uni-potsdam.de/v2.0/. Twelve of 34 plant-specific TF families were found in at least one algal species, indicating their early evolutionary origin. Twenty-two plant-specific TF families and one plant-specific TR family were not observed in algae, suggesting their specific association with developmental or physiological processes characteristic to multicellular plants. We also analyzed the occurrence of proteins that constitute the light-regulated transcriptional network in angiosperms and found putative algal orthologs for most of them. Our analysis provides a solid ground for future experimental studies aiming at deciphering the transcriptional regulatory networks in green algae.}, } @article {pmid18482401, year = {2008}, author = {Urushihara, H}, title = {Developmental biology of the social amoeba: history, current knowledge and prospects.}, journal = {Development, growth & differentiation}, volume = {50 Suppl 1}, number = {}, pages = {S277-81}, doi = {10.1111/j.1440-169X.2008.01013.x}, pmid = {18482401}, issn = {1440-169X}, mesh = {Amoeba/*physiology ; Animals ; Cell Differentiation ; Chemotaxis ; Developmental Biology/*methods ; Dictyosteliida/physiology ; Dictyostelium/*metabolism ; Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Models, Biological ; Signal Transduction ; }, abstract = {The cellular slime molds are known as the social amoebae because they conditionally construct multicellular forms in which cell differentiation takes place. Among them, Dictyostelium discoideum has many advantages as an experimental system and is widely used as a model organism. This review aims to reconsider how it has contributed to the understanding of developmental mechanisms and what should be done in the future. Chemotaxis, cell differentiation, genome and transcriptome, and the ecological and evolutionary implications of development are discussed.}, } @article {pmid18467345, year = {2008}, author = {Kim, J and Kim, TG and Jung, SH and Kim, JR and Park, T and Heslop-Harrison, P and Cho, KH}, title = {Evolutionary design principles of modules that control cellular differentiation: consequences for hysteresis and multistationarity.}, journal = {Bioinformatics (Oxford, England)}, volume = {24}, number = {13}, pages = {1516-1522}, doi = {10.1093/bioinformatics/btn229}, pmid = {18467345}, issn = {1367-4811}, mesh = {Cell Differentiation/*physiology ; Computer Simulation ; *Evolution, Molecular ; Feedback/physiology ; Gene Expression Regulation, Developmental/*physiology ; *Models, Genetic ; Proteome/*metabolism ; Signal Transduction/*physiology ; }, abstract = {MOTIVATION: Gene regulatory networks (GRNs) govern cellular differentiation processes and enable construction of multicellular organisms from single cells. Although such networks are complex, there must be evolutionary design principles that shape the network to its present form, gaining complexity from simple modules.

RESULTS: To isolate particular design principles, we have computationally evolved random regulatory networks with a preference to result either in hysteresis (switching threshold depending on current state), or in multistationarity (having multiple steady states), two commonly observed dynamical features of GRNs related to differentiation processes. We have analyzed the resulting evolved networks and compared their structures and characteristics with real GRNs reported from experiments.

CONCLUSION: We found that the artificially evolved networks have particular topologies and it was notable that these topologies share important features and similarities with the real GRNs, particularly in contrasting properties of positive and negative feedback loops. We conclude that the structures of real GRNs are consistent with selection to favor one or other of the dynamical features of multistationarity or hysteresis.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid18461162, year = {2008}, author = {Shalchian-Tabrizi, K and Minge, MA and Espelund, M and Orr, R and Ruden, T and Jakobsen, KS and Cavalier-Smith, T}, title = {Multigene phylogeny of choanozoa and the origin of animals.}, journal = {PloS one}, volume = {3}, number = {5}, pages = {e2098}, pmid = {18461162}, issn = {1932-6203}, mesh = {Animals ; Cell Adhesion ; Dinoflagellida/classification/genetics/physiology ; Eukaryota/*classification/*genetics/physiology ; Evolution, Molecular ; Genetic Variation ; Humans ; *Origin of Life ; *Phylogeny ; Protein-Tyrosine Kinases/metabolism ; Signal Transduction ; Species Specificity ; }, abstract = {Animals are evolutionarily related to fungi and to the predominantly unicellular protozoan phylum Choanozoa, together known as opisthokonts. To establish the sequence of events when animals evolved from unicellular ancestors, and understand those key evolutionary transitions, we need to establish which choanozoans are most closely related to animals and also the evolutionary position of each choanozoan group within the opisthokont phylogenetic tree. Here we focus on Ministeria vibrans, a minute bacteria-eating cell with slender radiating tentacles. Single-gene trees suggested that it is either the closest unicellular relative of animals or else sister to choanoflagellates, traditionally considered likely animal ancestors. Sequencing thousands of Ministeria protein genes now reveals about 14 with domains of key significance for animal cell biology, including several previously unknown from deeply diverging Choanozoa, e.g. domains involved in hedgehog, Notch and tyrosine kinase signaling or cell adhesion (cadherin). Phylogenetic trees using 78 proteins show that Ministeria is not sister to animals or choanoflagellates (themselves sisters to animals), but to Capsaspora, another protozoan with thread-like (filose) tentacles. The Ministeria/Capsaspora clade (new class Filasterea) is sister to animals and choanoflagellates, these three groups forming a novel clade (filozoa) whose ancestor presumably evolved filose tentacles well before they aggregated as a periciliary collar in the choanoflagellate/sponge common ancestor. Our trees show ichthyosporean choanozoans as sisters to filozoa; a fusion between ubiquitin and ribosomal small subunit S30 protein genes unifies all holozoa (filozoa plus Ichthyosporea), being absent in earlier branching eukaryotes. Thus, several successive evolutionary innovations occurred among their unicellular closest relatives prior to the origin of the multicellular body-plan of animals.}, } @article {pmid18451871, year = {2008}, author = {Birge, RB and Ucker, DS}, title = {Innate apoptotic immunity: the calming touch of death.}, journal = {Cell death and differentiation}, volume = {15}, number = {7}, pages = {1096-1102}, doi = {10.1038/cdd.2008.58}, pmid = {18451871}, issn = {1350-9047}, mesh = {Animals ; Apoptosis/genetics/*immunology ; Cytokines/immunology ; Humans ; *Immune Tolerance/genetics ; *Immunity, Innate/genetics ; Inflammation/genetics/*immunology/pathology ; Phagocytes/*immunology ; *Phagocytosis ; Phosphatidylserines/immunology ; Repressor Proteins/immunology ; Transcription, Genetic/immunology ; }, abstract = {Apoptotic cell death is an essential and highly ordered process that contributes to both the development and the homeostasis of multicellular organisms. It is associated with dramatic biochemical and cell biological events within the dying cell, including fragmentation of the nucleus and the redistribution of intracellular proteins and membrane lipids. It has long been apparent that phagocytic clearance of the cell corpse is an integral part of the apoptotic process; apoptotic clearance also may be essential in tissue homeostasis. During the cell death process, apoptotic cells acquire new cell surface determinants for specific recognition by responder phagocytes and suppression of immune responsiveness. Recent studies indicate that these determinants are well conserved throughout metazoan evolution; remarkably, their recognition shows no species-specific restriction. Professional and non-professional phagocytes recognize and respond to apoptotic cells similarly, notably with the immediate-early transcriptional repression of a variety of specific genes including those encoding inflammatory cytokines. Secondary responses following engulfment of the apoptotic corpse, utilizing several distinct mechanisms, enhance and sustain this apoptotic suppression. In this review, we highlight the central role of apoptotic cells in innate homeostatic regulation of immunity.}, } @article {pmid18447908, year = {2008}, author = {Sands, CJ and Convey, P and Linse, K and McInnes, SJ}, title = {Assessing meiofaunal variation among individuals utilising morphological and molecular approaches: an example using the Tardigrada.}, journal = {BMC ecology}, volume = {8}, number = {}, pages = {7}, pmid = {18447908}, issn = {1472-6785}, mesh = {Animals ; Biodiversity ; Body Size ; DNA/isolation & purification ; *Evolution, Molecular ; *Genetic Variation ; Invertebrates/anatomy & histology/classification/*genetics ; Likelihood Functions ; *Phylogeny ; Polymerase Chain Reaction ; Random Amplified Polymorphic DNA Technique ; Soil ; Specimen Handling/*methods ; }, abstract = {BACKGROUND: Meiofauna - multicellular animals captured between sieve size 45 mum and 1000 mum - are a fundamental component of terrestrial, and marine benthic ecosystems, forming an integral element of food webs, and playing a critical roll in nutrient recycling. Most phyla have meiofaunal representatives and studies of these taxa impact on a wide variety of sub-disciplines as well as having social and economic implications. However, studies of variation in meiofauna are presented with several important challenges. Isolating individuals from a sample substrate is a time consuming process, and identification requires increasingly scarce taxonomic expertise. Finding suitable morphological characters in many of these organisms is often difficult even for experts. Molecular markers are extremely useful for identifying variation in morphologically conserved organisms. However, for many species markers need to be developed de novo, while DNA can often only be extracted from pooled samples in order to obtain sufficient quantity and quality. Importantly, multiple independent markers are required to reconcile gene evolution with species evolution. In this primarily methodological paper we provide a proof of principle of a novel and effective protocol for the isolation of meiofauna from an environmental sample. We also go on to illustrate examples of the implications arising from subsequent screening for genetic variation at the level of the individual using ribosomal, mitochondrial and single copy nuclear markers.

RESULTS: To isolate individual tardigrades from their habitat substrate we used a non-toxic density gradient media that did not interfere with downstream biochemical processes. Using a simple DNA release technique and nested polymerase chain reaction with universal primers we were able amplify multi-copy and, to some extent, single copy genes from individual tardigrades. Maximum likelihood trees from ribosomal 18S, mitochondrial cytochrome oxidase subunit 1, and the single copy nuclear gene Wingless support a recent study indicating that the family Hypsibiidae is a non-monophyletic group. From these sequences we were able to detect variation between individuals at each locus that allowed us to identify the presence of cryptic taxa that would otherwise have been overlooked.

CONCLUSION: Molecular results obtained from individuals, rather than pooled samples, are a prerequisite to enable levels of variation to be placed into context. In this study we have provided a proof of principle of this approach for meiofaunal tardigrades, an important group of soil biota previously not considered amenable to such studies, thereby paving the way for more comprehensive phylogenetic studies using multiple nuclear markers, and population genetic studies.}, } @article {pmid19841663, year = {2008}, author = {Meagher, RB and Kandasamy, MK and McKinney, EC}, title = {Multicellular development and protein-protein interactions.}, journal = {Plant signaling & behavior}, volume = {3}, number = {5}, pages = {333-336}, pmid = {19841663}, issn = {1559-2316}, support = {R01 GM036397/GM/NIGMS NIH HHS/United States ; }, abstract = {The macroevolution of organs and tissues in higher plants and animals may have been contingent upon the expansion of numerous gene families encoding interacting proteins. For example, there are dozens of gene families encoding actin cytoskeletal proteins that elaborate intercellular structures influencing development. Once gene family members evolve compartmentalized expression, protein isovariants are free to coevolve new interacting partners that may be incompatible with other related protein networks. Ancient classes of actin isovariants and actin-binding proteins are clear examples of such coevolving networks. Ectopic expression and suppression studies were used to dissect these interactions. In higher plants, the ectopic expression of a reproductive actin isovariant in vegetative cell types causes aberrant reorganization of the F-actin cytoskeleton and bizarre development of most organs and tissues. In contrast, overexpression of vegetative actin in vegetative cell types has little effect. The extreme ectopic actin expression phenotypes are suppressed by the coectopic expression of reproductive profilin or actin depolymerizing factor (ADF/cofilin) isovariants, but not by the overexpression of vegetative profilin or ADF. These data provide evidence for the coevolution of organ-specific protein-protein interactions. Thus, understanding the contingent relationships between the evolution of organ-specific isovariant networks and organ origination may be key to explaining multicellular development.}, } @article {pmid18415981, year = {2007}, author = {Gunbin, KV and Afonnikov, DA and Kolchanov, NA}, title = {The evolution of the Hh-signaling pathway genes: a computer-assisted study.}, journal = {In silico biology}, volume = {7}, number = {3}, pages = {333-354}, pmid = {18415981}, issn = {1386-6338}, mesh = {Algorithms ; Animals ; Computer Simulation ; *Evolution, Molecular ; Hedgehog Proteins/*genetics ; Humans ; Invertebrates/physiology ; Proteins/chemistry/*genetics ; Signal Transduction/physiology ; Transcription Factors/*genetics ; }, abstract = {Positive selection of genes that comprise signaling cascades and play the paramount role in the development of multicellular organisms is critical to our understanding of the reasons for the evolution of embryonic development. In this work, we analyze the evolution of 9 genes involved in the function of the Hh signaling cascade. We demonstrated that positive selection is a characteristic feature of the protein domains, encoded by gene regions, whose functions are related to the molecular mechanisms of development. We also found that the positive selection of Hh-signaling cascade transcription factors, morphogens, their development-related receptors and intracellular signal transduction factors are related to the divergence of the Bilateria taxonomic types.}, } @article {pmid18403826, year = {2008}, author = {Newman, SA and Bhat, R}, title = {Dynamical patterning modules: physico-genetic determinants of morphological development and evolution.}, journal = {Physical biology}, volume = {5}, number = {1}, pages = {015008}, doi = {10.1088/1478-3975/5/1/015008}, pmid = {18403826}, issn = {1478-3975}, mesh = {Animals ; *Biological Evolution ; Biophysical Phenomena ; *Biophysics ; Body Patterning/*genetics ; Cell Adhesion ; Cell Differentiation ; Embryonic Development/genetics ; Evolution, Molecular ; *Models, Biological ; }, abstract = {The shapes and forms of multicellular organisms arise by the generation of new cell states and types and changes in the numbers and rearrangements of the various kinds of cells. While morphogenesis and pattern formation in all animal species are widely recognized to be mediated by the gene products of an evolutionarily conserved 'developmental-genetic toolkit', the link between these molecular players and the physics underlying these processes has been generally ignored. This paper introduces the concept of 'dynamical patterning modules' (DPMs), units consisting of one or more products of the 'toolkit' genes that mobilize physical processes characteristic of chemically and mechanically excitable meso- to macroscopic systems such as cell aggregates: cohesion, viscoelasticity, diffusion, spatiotemporal heterogeneity based on lateral inhibition and multistable and oscillatory dynamics. We suggest that ancient toolkit gene products, most predating the emergence of multicellularity, assumed novel morphogenetic functions due to change in the scale and context inherent to multicellularity. We show that DPMs, acting individually and in concert with each other, constitute a 'pattern language' capable of generating all metazoan body plans and organ forms. The physical dimension of developmental causation implies that multicellular forms during the explosive radiation of animal body plans in the middle Cambrian, approximately 530 million years ago, could have explored an extensive morphospace without concomitant genotypic change or selection for adaptation. The morphologically plastic body plans and organ forms generated by DPMs, and their ontogenetic trajectories, would subsequently have been stabilized and consolidated by natural selection and genetic drift. This perspective also solves the apparent 'molecular homology-analogy paradox', whereby widely divergent modern animal types utilize the same molecular toolkit during development by proposing, in contrast to the Neo-Darwinian principle, that phenotypic disparity early in evolution occurred in advance of, rather than closely tracked, genotypic change.}, } @article {pmid18398465, year = {2008}, author = {Wasserstrom, A and Adar, R and Shefer, G and Frumkin, D and Itzkovitz, S and Stern, T and Shur, I and Zangi, L and Kaplan, S and Harmelin, A and Reisner, Y and Benayahu, D and Tzahor, E and Segal, E and Shapiro, E}, title = {Reconstruction of cell lineage trees in mice.}, journal = {PloS one}, volume = {3}, number = {4}, pages = {e1939}, pmid = {18398465}, issn = {1932-6203}, mesh = {Animals ; B-Lymphocytes/cytology ; Cell Differentiation ; *Cell Lineage ; Hematopoietic Stem Cells/cytology ; Kidney/cytology ; Killer Cells, Natural/cytology ; Mesenchymal Stem Cells/cytology ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/cytology ; Mutation ; Oocytes/metabolism ; Satellite Cells, Skeletal Muscle/cytology ; Stem Cells/*cytology ; }, abstract = {The cell lineage tree of a multicellular organism represents its history of cell divisions from the very first cell, the zygote. A new method for high-resolution reconstruction of parts of such cell lineage trees was recently developed based on phylogenetic analysis of somatic mutations accumulated during normal development of an organism. In this study we apply this method in mice to reconstruct the lineage trees of distinct cell types. We address for the first time basic questions in developmental biology of higher organisms, namely what is the correlation between the lineage relation among cells and their (1) function, (2) physical proximity and (3) anatomical proximity. We analyzed B-cells, kidney-, mesenchymal- and hematopoietic-stem cells, as well as satellite cells, which are adult skeletal muscle stem cells isolated from their niche on the muscle fibers (myofibers) from various skeletal muscles. Our results demonstrate that all analyzed cell types are intermingled in the lineage tree, indicating that none of these cell types are single exclusive clones. We also show a significant correlation between the physical proximity of satellite cells within muscles and their lineage. Furthermore, we show that satellite cells obtained from a single myofiber are significantly clustered in the lineage tree, reflecting their common developmental origin. Lineage analysis based on somatic mutations enables performing high resolution reconstruction of lineage trees in mice and humans, which can provide fundamental insights to many aspects of their development and tissue maintenance.}, } @article {pmid18392877, year = {2008}, author = {Beermann, A and Schröder, R}, title = {Sites of Fgf signalling and perception during embryogenesis of the beetle Tribolium castaneum.}, journal = {Development genes and evolution}, volume = {218}, number = {3-4}, pages = {153-167}, pmid = {18392877}, issn = {0949-944X}, mesh = {Amino Acid Sequence ; Animals ; Brain/embryology/metabolism ; Embryo, Nonmammalian ; Embryonic Development/*genetics ; Fibroblast Growth Factors/genetics/*metabolism/physiology ; Gene Expression Regulation, Developmental ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Receptors, Fibroblast Growth Factor/genetics/metabolism ; Sequence Homology, Amino Acid ; Signal Transduction/genetics ; Tissue Distribution ; Tribolium/*embryology/*genetics/metabolism ; }, abstract = {The development of multicellular embryos depends on coordinated cell-to-cell signalling events. Among the numerous cell-signalling pathways, fibroblast growth factors (FGFs) are involved in important processes during embryogenesis, such as mesoderm formation during gastrulation and growth. In vertebrates, the Fgf superfamily consists of 22 family members, whereas only few FGFs are contained in the less complex genomes of insects and worms. In the recently sequenced genome of the beetle Tribolium, we identified four Fgf family members representing three subfamilies. Tribolium has Fgf1 genes that are absent in Drosophila but known from vertebrates. By phylogenetic analysis and microsynteny to Drosophila, we further classify Tc-fgf 8 as an ancestor of pyramus and thisbe, the fly Fgf8 genes. Tc-fgf8 expression in the growth zone suggests an involvement in mesoderm formation. In the embryonic head, expression of Tc-fgf8 subdivides the brain into a larger anterior and a smaller posterior region. The Fgf Tc-branchless is expressed in the embryonic tracheal placodes and in various gland-like structures. The expression patterns of the only Tribolium Fgf receptor and the adaptor molecule Downstream-of-Fgfr are largely congruent with Tc-Fgf8 and Tc-bnl. Thus, in contrast to Drosophila, only one Fgf receptor canalises Fgf signalling in different tissues in Tribolium. Our findings significantly advance our understanding of the evolution of Fgf signalling in insects.}, } @article {pmid18390552, year = {2008}, author = {Li, W and Young, SL and King, N and Miller, WT}, title = {Signaling properties of a non-metazoan Src kinase and the evolutionary history of Src negative regulation.}, journal = {The Journal of biological chemistry}, volume = {283}, number = {22}, pages = {15491-15501}, pmid = {18390552}, issn = {0021-9258}, support = {R01 CA058530/CA/NCI NIH HHS/United States ; R01 CA058530-14/CA/NCI NIH HHS/United States ; CA 58530/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; CSK Tyrosine-Protein Kinase ; Eukaryota/*enzymology/genetics ; *Evolution, Molecular ; Mammals/genetics/metabolism ; Molecular Sequence Data ; Protein-Tyrosine Kinases/genetics/metabolism ; Protozoan Proteins/genetics/*metabolism ; Signal Transduction/*physiology ; src Homology Domains/physiology ; src-Family Kinases/genetics/*metabolism ; }, abstract = {Choanoflagellates, unicellular organisms that are closely related to metazoans, possess cell adhesion and signaling proteins previously thought to be unique to animals, suggesting that these components may have played roles in the evolution of metazoan multicellularity. We have cloned, expressed, and purified the nonreceptor tyrosine kinase MbSrc1 from the choanoflagellate Monosiga brevicollis. The kinase has the same domain arrangement as mammalian Src kinases, and we find that the individual Src homology 3 (SH3), SH2, and catalytic domains have similar functions to their mammalian counterparts. In contrast to mammalian c-Src, the SH2 and catalytic domains of MbSrc1 do not appear to be functionally coupled. We cloned and expressed the M. brevicollis homolog of c-Src C-terminal kinase (MbCsk) and showed that it phosphorylates the C terminus of MbSrc1, yet this phosphorylation does not inhibit MbSrc to the same degree seen in the mammalian Src/Csk pair. Thus, Src autoinhibition likely evolved more recently within the metazoan lineage, and it may have played a role in the establishment of intercellular signaling in metazoans.}, } @article {pmid18385221, year = {2008}, author = {Cai, X}, title = {Unicellular Ca2+ signaling 'toolkit' at the origin of metazoa.}, journal = {Molecular biology and evolution}, volume = {25}, number = {7}, pages = {1357-1361}, doi = {10.1093/molbev/msn077}, pmid = {18385221}, issn = {1537-1719}, mesh = {Amino Acid Sequence ; Animals ; Calcium/*metabolism ; Calcium Channels/classification/genetics/metabolism ; Calcium Signaling/*physiology ; Humans ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {Ca(2+) signaling pathways control many physiological processes in almost all types of animal cells such as fertilization, muscle contraction, hormone release, and learning and memory. Each animal cell type expresses a unique group of molecules from the Ca(2+) signaling 'toolkit' to control spatiotemporal patterns of Ca(2+) signaling. It is generally believed that the complex Ca(2+) signaling 'toolkit' has arisen from the ancestral multicellular organisms to fit unique physiological roles of specialized cell types. Here, we demonstrate for the first time the presence of an extensive Ca(2+) signaling 'toolkit' in the unicellular choanoflagellate Monosiga brevicollis. Choanoflagellates possess homologues of various types of animal plasma membrane Ca(2+) channels including the store-operated channel, ligand-operated channels, voltage-operated channels, second messenger-operated channels, and 5 out of 6 animal transient receptor potential channel families. Choanoflagellates also contain homologues of inositol 1,4,5-trisphosphate receptors. Furthermore, choanoflagellates master a complete set of Ca(2+) removal systems including plasma membrane and sarco/endoplasmic reticulum Ca(2+) ATPases and homologues of 3 animal cation/Ca(2+) exchanger families. Therefore, a complex Ca(2+) signaling 'toolkit' might have evolved before the emergence of multicellular animals.}, } @article {pmid18375012, year = {2008}, author = {Sachs, JL}, title = {Resolving the first steps to multicellularity.}, journal = {Trends in ecology & evolution}, volume = {23}, number = {5}, pages = {245-248}, doi = {10.1016/j.tree.2008.02.003}, pmid = {18375012}, issn = {0169-5347}, mesh = {*Biological Evolution ; Chlorophyta/*cytology ; }, abstract = {Multicellular life has evolved many times, yet each origin requires free cells to integrate unselfishly into a higher-level individual. How can such transitions evolve? In a new paper, Herron and Michod investigate the recent origins of multicellularity in colonial algae. Their phylogenetic reconstructions provide a striking dissection of early steps, and altruistic traits are at the crux of it. Key evolutionary reversals are also revealed, where cellular selfishness might have thwarted multicellular integration.}, } @article {pmid18373660, year = {2008}, author = {Eppley, SM and Jesson, LK}, title = {Moving to mate: the evolution of separate and combined sexes in multicellular organisms.}, journal = {Journal of evolutionary biology}, volume = {21}, number = {3}, pages = {727-736}, doi = {10.1111/j.1420-9101.2008.01524.x}, pmid = {18373660}, issn = {1420-9101}, mesh = {Animals ; *Biological Evolution ; Computer Simulation ; Disorders of Sex Development/genetics ; Invertebrates/genetics ; Models, Biological ; Phylogeny ; Plants ; Reproduction/genetics ; *Sex ; *Sex Characteristics ; Vertebrates/genetics ; }, abstract = {Which conditions favour the evolution of hermaphroditism or separate sexes? One classical hypothesis states that an organism's mode of locomotion (if any) when searching for a mate should influence breeding system evolution. We used published phylogenies to reconstruct evolutionary changes in adult mate-search efficiency and breeding systems among multicellular organisms. Employing maximum-likelihood analyses, we found that changes in adult mate-search efficiency are significantly correlated with changes in breeding system, and this result is robust to uncertainties in the phylogenies. These data provide the first statistical support, across a broad range of taxa, for the hypothesis that breeding systems and mate-search efficiency did not evolve independently. We discuss our results in context with other causal factors, such as inbreeding avoidance and sexual specialization, likely to affect breeding system evolution.}, } @article {pmid18369424, year = {2008}, author = {Basanta, D and Miodownik, M and Baum, B}, title = {The evolution of robust development and homeostasis in artificial organisms.}, journal = {PLoS computational biology}, volume = {4}, number = {3}, pages = {e1000030}, pmid = {18369424}, issn = {1553-7358}, support = {BBS/B/02495/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Biomimetics/*methods ; Cell Communication/*physiology ; *Cell Physiological Phenomena ; Computer Simulation ; Homeostasis/*physiology ; Humans ; *Models, Biological ; Morphogenesis/*physiology ; Regeneration/*physiology ; }, abstract = {During embryogenesis, multicellular animals are shaped via cell proliferation, cell rearrangement, and apoptosis. At the end of development, tissue architecture is then maintained through balanced rates of cell proliferation and loss. Here, we take an in silico approach to look for generic systems features of morphogenesis in multicellular animals that arise as a consequence of the evolution of development. Using artificial evolution, we evolved cellular automata-based digital organisms that have distinct embryonic and homeostatic phases of development. Although these evolved organisms use a variety of strategies to maintain their form over time, organisms of different types were all found to rapidly recover from environmental damage in the form of wounds. This regenerative response was most robust in an organism with a stratified tissue-like architecture. An evolutionary analysis revealed that evolution itself contributed to the ability of this organism to maintain its form in the face of genetic and environmental perturbation, confirming the results of previous studies. In addition, the exceptional robustness of this organism to surface injury was found to result from an upward flux of cells, driven in part by cell divisions with a stable niche at the tissue base. Given the general nature of the model, our results lead us to suggest that many of the robust systems properties observed in real organisms, including scar-free wound-healing in well-protected embryos and the layered tissue architecture of regenerating epithelial tissues, may be by-products of the evolution of morphogenesis, rather than the direct result of selection.}, } @article {pmid18351884, year = {2008}, author = {Tannenbaum, E}, title = {Comparison of three replication strategies in complex multicellular organisms: asexual replication, sexual replication with identical gametes, and sexual replication with distinct sperm and egg gametes.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {77}, number = {1 Pt 1}, pages = {011915}, doi = {10.1103/PhysRevE.77.011915}, pmid = {18351884}, issn = {1539-3755}, mesh = {Animals ; *Biological Evolution ; Computer Simulation ; *Genetics, Population ; Humans ; *Models, Genetic ; Reproduction/*genetics ; *Selection, Genetic ; }, abstract = {This paper studies the mutation-selection balance in three simplified replication models. The first model considers a population of organisms replicating via the production of asexual spores. The second model considers a sexually replicating population that produces identical gametes. The third model considers a sexually replicating population that produces distinct sperm and egg gametes. All models assume diploid organisms whose genomes consist of two chromosomes, each of which is taken to be functional if equal to some master sequence, and defective otherwise. In the asexual population, the asexual diploid spores develop directly into adult organisms. In the sexual populations, the haploid gametes enter a haploid pool, where they may fuse with other haploids. The resulting immature diploid organisms then proceed to develop into mature organisms. Based on an analysis of all three models, we find that, as organism size increases, a sexually replicating population can only outcompete an asexually replicating population if the adult organisms produce distinct sperm and egg gametes. A sexual replication strategy that is based on the production of large numbers of sperm cells to fertilize a small number of eggs is found to be necessary in order to maintain a sufficiently low cost for sex for the strategy to be selected for over a purely asexual strategy. We discuss the usefulness of this model in understanding the evolution and maintenance of sexual replication as the preferred replication strategy in complex, multicellular organisms.}, } @article {pmid18349049, year = {2008}, author = {Jia, XY and Xu, CY and Jing, RL and Li, RZ and Mao, XG and Wang, JP and Chang, XP}, title = {Molecular cloning and characterization of wheat calreticulin (CRT) gene involved in drought-stressed responses.}, journal = {Journal of experimental botany}, volume = {59}, number = {4}, pages = {739-751}, doi = {10.1093/jxb/erm369}, pmid = {18349049}, issn = {1460-2431}, mesh = {Amino Acid Sequence ; Calreticulin/*genetics/*metabolism ; Cloning, Molecular ; *Desiccation ; Disasters ; Gene Expression Profiling ; Gene Expression Regulation, Plant/drug effects ; Genome, Plant ; Molecular Sequence Data ; Phylogeny ; Plant Roots/cytology ; Polyethylene Glycols/pharmacology ; Triticum/drug effects/*genetics/*metabolism ; Water/*metabolism ; }, abstract = {Calreticulin (CRT) is a highly conserved and ubiquitously expressed Ca(2+)-binding protein in multicellular eukaryotes. CRT plays a crucial role in many cellular processes including Ca(2+) storage and release, protein synthesis, and molecular chaperone activity. To elucidate the function of CRTs in plant responses against drought, a main abiotic stress limiting cereal crop production worldwide, a full-length cDNA encoding calreticulin protein namely TaCRT was isolated from wheat (Triticum aestivum L.). The deduced amino acid sequence of TaCRT shares high homology with other plant CRTs. Phylogenetic analysis indicates that TaCRT cDNA clone encodes a wheat CRT3 isoform. Southern analysis suggests that the wheat genome contains three copies of TaCRT. Subcellular locations of TaCRT were the cytoplasm and nucleus, evidenced by transient expression of GFP fused with TaCRT in onion epidermal cells. Enhanced accumulation of TaCRT transcript was observed in wheat seedlings in response to PEG-induced drought stress. To investigate further whether TaCRT is involved in the drought-stress response, transgenic plants were constructed. Compared to the wild-type and GFP-expressing plants, TaCRT-overexpressing tobacco (Nicotiana benthamiana) plants grew better and exhibited less wilt under the drought stress. Moreover, TaCRT-overexpressing plants exhibited enhanced drought resistance to water deficit, as shown by their capacity to maintain higher WUE (water use efficiency), WRA (water retention ability), RWC (relative water content), and lower MDR (membrane damaging ratio) (P < or = 0.01) under water-stress conditions. In conclusion, a cDNA clone encoding wheat CRT was successfully isolated and the results suggest that TaCRT is involved in the plant response to drought stress, indicating a potential in the transgenic improvements of plant water-stress.}, } @article {pmid18348154, year = {2008}, author = {Dunny, GM and Brickman, TJ and Dworkin, M}, title = {Multicellular behavior in bacteria: communication, cooperation, competition and cheating.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {30}, number = {4}, pages = {296-298}, doi = {10.1002/bies.20740}, pmid = {18348154}, issn = {1521-1878}, mesh = {Bacteria/metabolism ; *Bacterial Physiological Phenomena ; Biofilms ; Cell Communication ; Colony Count, Microbial ; Evolution, Molecular ; Gene Expression Regulation, Bacterial ; Microbiological Techniques ; Models, Biological ; *Mutation ; Pseudomonas aeruginosa/*metabolism ; }, abstract = {The sociobiology of bacteria, largely unappreciated and ignored by the microbiology research community two decades ago is now a major research area, catalyzed to a significant degree by studies of communication and cooperative behavior among the myxobacteria and in quorum sensing (QS) and biofilm formation by pseudomonads and other microbes. Recently, the topic of multicellular cooperative behaviors among bacteria has been increasingly considered in the context of evolutionary biology. Here we discuss the significance of two recent studies of the phenomenon of "cheating" mutants and their exploitation of cooperating microbial populations of Pseudomonas aeruginosa.}, } @article {pmid18328773, year = {2008}, author = {Breitwieser, GE}, title = {Extracellular calcium as an integrator of tissue function.}, journal = {The international journal of biochemistry & cell biology}, volume = {40}, number = {8}, pages = {1467-1480}, pmid = {18328773}, issn = {1357-2725}, support = {R01 GM077563/GM/NIGMS NIH HHS/United States ; R01 GM077563-02/GM/NIGMS NIH HHS/United States ; GM077563/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Calcium/*physiology ; Calcium Signaling/*physiology ; Membrane Microdomains/physiology ; Receptors, Calcium-Sensing/physiology ; }, abstract = {The past several decades of research into calcium signaling have focused on intracellular calcium (Ca(i)(2+)), revealing both exquisite spatial and dynamic control of this potent second messenger. Our understanding of Ca(i)(2+) signaling has benefited from the evolution of cell culture methods, development of high affinity fluorescent calcium indicators (both membrane-permeant small molecules and genetically encoded proteins), and high-resolution fluorescence microscopy. As our understanding of single cell calcium dynamics has increased, translational efforts have attempted to push calcium signaling studies back into tissues, organs and whole animals. Emerging results from these more complicated, diffusion-limited systems have begun to define a role for extracellular calcium (Ca(o)(2+)) as an agonist, spurred by the cloning and characterization of a G protein-coupled receptor activated by Ca(o)(2+) (the calcium sensing receptor, CaR). Here, we review the current state-of-the art for measurement of Ca(o)(2+) fluctuations, and the evidence that fluctuations in Ca(o)(2+) can act as primary signals regulating cell function. Current results suggest that Ca(o)(2+) in bone and epidermis may act as a chemotactic homing signal, targeting cells to the appropriate tissue locations prior to initiation of the differentiation program. Ca(i)(2+) signaling-mediated Ca(o)(2+) fluctuations in interstitial spaces may integrate cell signaling responses in multicellular networks through activation of CaR. Appreciation of the importance of Ca(o)(2+) fluctuations in coordinating cell function will likely spur identification of additional, niche-specific Ca(2+) sensors, and provide unique insights into the regulation of multicellular signaling networks.}, } @article {pmid18326026, year = {2008}, author = {Veening, JW and Stewart, EJ and Berngruber, TW and Taddei, F and Kuipers, OP and Hamoen, LW}, title = {Bet-hedging and epigenetic inheritance in bacterial cell development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {11}, pages = {4393-4398}, pmid = {18326026}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Bacillus subtilis/cytology/*genetics/*growth & development ; Cell Lineage ; Epigenesis, Genetic/*genetics ; Phylogeny ; Spores, Bacterial/cytology ; }, abstract = {Upon nutritional limitation, the bacterium Bacillus subtilis has the capability to enter the irreversible process of sporulation. This developmental process is bistable, and only a subpopulation of cells actually differentiates into endospores. Why a cell decides to sporulate or not to do so is poorly understood. Here, through the use of time-lapse microscopy, we follow the growth, division, and differentiation of individual cells to identify elements of cell history and ancestry that could affect this decision process. These analyses show that during microcolony development, B. subtilis uses a bet-hedging strategy whereby some cells sporulate while others use alternative metabolites to continue growth, providing the latter subpopulation with a reproductive advantage. We demonstrate that B. subtilis is subject to aging. Nevertheless, the age of the cell plays no role in the decision of its fate. However, the physiological state of the cell's ancestor (more than two generations removed) does affect the outcome of cellular differentiation. We show that this epigenetic inheritance is based on positive feedback within the sporulation phosphorelay. The extended intergenerational "memory" caused by this autostimulatory network may be important for the development of multicellular structures such as fruiting bodies and biofilms.}, } @article {pmid18322464, year = {2008}, author = {Dunn, CW and Hejnol, A and Matus, DQ and Pang, K and Browne, WE and Smith, SA and Seaver, E and Rouse, GW and Obst, M and Edgecombe, GD and Sørensen, MV and Haddock, SH and Schmidt-Rhaesa, A and Okusu, A and Kristensen, RM and Wheeler, WC and Martindale, MQ and Giribet, G}, title = {Broad phylogenomic sampling improves resolution of the animal tree of life.}, journal = {Nature}, volume = {452}, number = {7188}, pages = {745-749}, doi = {10.1038/nature06614}, pmid = {18322464}, issn = {1476-4687}, mesh = {Animals ; Bayes Theorem ; Classification/*methods ; Computational Biology ; Databases, Genetic ; Evolution, Molecular ; Expressed Sequence Tags ; Gene Library ; Humans ; Markov Chains ; *Phylogeny ; Reproducibility of Results ; Sample Size ; Sensitivity and Specificity ; }, abstract = {Long-held ideas regarding the evolutionary relationships among animals have recently been upended by sometimes controversial hypotheses based largely on insights from molecular data. These new hypotheses include a clade of moulting animals (Ecdysozoa) and the close relationship of the lophophorates to molluscs and annelids (Lophotrochozoa). Many relationships remain disputed, including those that are required to polarize key features of character evolution, and support for deep nodes is often low. Phylogenomic approaches, which use data from many genes, have shown promise for resolving deep animal relationships, but are hindered by a lack of data from many important groups. Here we report a total of 39.9 Mb of expressed sequence tags from 29 animals belonging to 21 phyla, including 11 phyla previously lacking genomic or expressed-sequence-tag data. Analysed in combination with existing sequences, our data reinforce several previously identified clades that split deeply in the animal tree (including Protostomia, Ecdysozoa and Lophotrochozoa), unambiguously resolve multiple long-standing issues for which there was strong conflicting support in earlier studies with less data (such as velvet worms rather than tardigrades as the sister group of arthropods), and provide molecular support for the monophyly of molluscs, a group long recognized by morphologists. In addition, we find strong support for several new hypotheses. These include a clade that unites annelids (including sipunculans and echiurans) with nemerteans, phoronids and brachiopods, molluscs as sister to that assemblage, and the placement of ctenophores as the earliest diverging extant multicellular animals. A single origin of spiral cleavage (with subsequent losses) is inferred from well-supported nodes. Many relationships between a stable subset of taxa find strong support, and a diminishing number of lineages remain recalcitrant to placement on the tree.}, } @article {pmid18321378, year = {2008}, author = {McGuire, AM and Pearson, MD and Neafsey, DE and Galagan, JE}, title = {Cross-kingdom patterns of alternative splicing and splice recognition.}, journal = {Genome biology}, volume = {9}, number = {3}, pages = {R50}, pmid = {18321378}, issn = {1474-760X}, support = {HHSN26620040001C//PHS HHS/United States ; }, mesh = {*Alternative Splicing ; Animals ; Base Sequence ; *Evolution, Molecular ; Exons ; Expressed Sequence Tags ; Genome ; *Introns ; Phylogeny ; *RNA Splice Sites ; *Transcription, Genetic ; }, abstract = {BACKGROUND: Variations in transcript splicing can reveal how eukaryotes recognize intronic splice sites. Retained introns (RIs) commonly appear when the intron definition (ID) mechanism of splice site recognition inconsistently identifies intron-exon boundaries, and cassette exons (CEs) are often caused by variable recognition of splice junctions by the exon definition (ED) mechanism. We have performed a comprehensive survey of alternative splicing across 42 eukaryotes to gain insight into how spliceosomal introns are recognized.

RESULTS: All eukaryotes we studied exhibit RIs, which appear more frequently than previously thought. CEs are also present in all kingdoms and most of the organisms in our analysis. We observe that the ratio of CEs to RIs varies substantially among kingdoms, while the ratio of competing 3' acceptor and competing 5' donor sites remains nearly constant. In addition, we find the ratio of CEs to RIs in each organism correlates with the length of its introns. In all 14 fungi we examined, as well as in most of the 9 protists, RIs far outnumber CEs. This differs from the trend seen in 13 multicellular animals, where CEs occur much more frequently than RIs. The six plants we analyzed exhibit intermediate proportions of CEs and RIs.

CONCLUSION: Our results suggest that most extant eukaryotes are capable of recognizing splice sites via both ID and ED, although ED is most common in multicellular animals and ID predominates in fungi and most protists.}, } @article {pmid18318857, year = {2008}, author = {Leander, BS}, title = {A hierarchical view of convergent evolution in microbial eukaryotes.}, journal = {The Journal of eukaryotic microbiology}, volume = {55}, number = {2}, pages = {59-68}, doi = {10.1111/j.1550-7408.2008.00308.x}, pmid = {18318857}, issn = {1066-5234}, mesh = {Animals ; *Biological Evolution ; *Eukaryota ; *Eukaryotic Cells ; *Phylogeny ; }, abstract = {Distinguishing convergent evolution from other causes of similarity in organisms is necessary for reconstructing phylogenetic relationships, inferring patterns of character evolution, and investigating the forces of natural selection. In contrast to animals and land plants, the pervasiveness and adaptive significance of convergent evolution in microbes has yet to be systematically explored or articulated. Convergent evolution in microbial eukaryotes, for instance, often involves very distantly related lineages with relatively limited repertoires of morphological features. These large phylogenetic distances weaken the role of ancestral developmental programs on the subsequent evolution of morphological characters, making convergent evolution between very distantly related lineages fundamentally different from convergent evolution between closely related lineages. This suggests that examples of convergence at different levels in the phylogenetic hierarchy offer different clues about the causes and processes of macroevolutionary diversification. Accordingly (and despite opinions to the contrary), I recognize three broad and overlapping categories of phenotypic convergence-"parallel", "proximate" and "ultimate"-that represent either (1) subcellular analogues, (2) subcellular analogues to multicellular systems (and vice versa), or (3) multicellular analogues. Microbial eukaryotes living in planktonic environments, interstitial environments, and the intestinal environments of metazoan hosts provide compelling examples of ultimate convergence. After describing selected examples in microbial eukaryotes, I suggest some future directions needed to more fully understand the hierarchical structure of convergent evolution and the overall history of life.}, } @article {pmid18315817, year = {2008}, author = {Nielsen, C}, title = {Six major steps in animal evolution: are we derived sponge larvae?.}, journal = {Evolution & development}, volume = {10}, number = {2}, pages = {241-257}, doi = {10.1111/j.1525-142X.2008.00231.x}, pmid = {18315817}, issn = {1525-142X}, mesh = {Animals ; *Biological Evolution ; Cnidaria/growth & development ; Ctenophora/growth & development ; Digestive System/growth & development ; Epithelium/growth & development ; Eukaryota/cytology ; Female ; Gastrulation ; Invertebrates/growth & development ; Larva/growth & development ; Male ; Mesoderm/growth & development ; Models, Biological ; Nervous System/growth & development ; Phylogeny ; Porifera/cytology/embryology/genetics/*growth & development ; }, abstract = {A review of the old and new literature on animal morphology/embryology and molecular studies has led me to the following scenario for the early evolution of the metazoans. The metazoan ancestor, "choanoblastaea," was a pelagic sphere consisting of choanocytes. The evolution of multicellularity enabled division of labor between cells, and an "advanced choanoblastaea" consisted of choanocytes and nonfeeding cells. Polarity became established, and an adult, sessile stage developed. Choanocytes of the upper side became arranged in a groove with the cilia pumping water along the groove. Cells overarched the groove so that a choanocyte chamber was formed, establishing the body plan of an adult sponge; the pelagic larval stage was retained but became lecithotrophic. The sponges radiated into monophyletic Silicea, Calcarea, and Homoscleromorpha. Homoscleromorph larvae show cell layers resembling true, sealed epithelia. A homoscleromorph-like larva developed an archenteron, and the sealed epithelium made extracellular digestion possible in this isolated space. This larva became sexually mature, and the adult sponge-stage was abandoned in an extreme progenesis. This eumetazoan ancestor, "gastraea," corresponds to Haeckel's gastraea. Trichoplax represents this stage, but with the blastopore spread out so that the endoderm has become the underside of the creeping animal. Another lineage developed a nervous system; this "neurogastraea" is the ancestor of the Neuralia. Cnidarians have retained this organization, whereas the Triploblastica (Ctenophora+Bilateria), have developed the mesoderm. The bilaterians developed bilaterality in a primitive form in the Acoelomorpha and in an advanced form with tubular gut and long Hox cluster in the Eubilateria (Protostomia+Deuterostomia). It is indicated that the major evolutionary steps are the result of suites of existing genes becoming co-opted into new networks that specify new structures. The evolution of the eumetazoan ancestor from a progenetic homoscleromorph larva implies that we, as well as all the other eumetazoans, are derived sponge larvae.}, } @article {pmid18296705, year = {2008}, author = {Warthmann, N and Das, S and Lanz, C and Weigel, D}, title = {Comparative analysis of the MIR319a microRNA locus in Arabidopsis and related Brassicaceae.}, journal = {Molecular biology and evolution}, volume = {25}, number = {5}, pages = {892-902}, doi = {10.1093/molbev/msn029}, pmid = {18296705}, issn = {1537-1719}, mesh = {Arabidopsis/*genetics ; Brassicaceae/*genetics ; Capsella/genetics ; Chromosomes, Artificial, Bacterial ; DNA, Plant ; Evolution, Molecular ; Genes, Plant ; MicroRNAs/*genetics/physiology ; Molecular Sequence Data ; Multigene Family ; Nucleic Acid Amplification Techniques ; Plants, Genetically Modified ; Polymorphism, Genetic ; Promoter Regions, Genetic ; RNA Precursors/genetics ; RNA, Plant/*genetics/physiology ; Sequence Alignment ; Species Specificity ; }, abstract = {MicroRNAs (miRNAs) are important regulators of gene expression in multicellular organisms. Yet, little is known about their molecular evolution. The 20- to 22-nt long miRNAs are processed in plants from foldbacks that are a few hundred base pairs in size. Often, these foldbacks are embedded in much larger precursor transcripts. To investigate functional constraints on sequence evolution of miRNA precursor genes, we have studied sequence variation in the precursor of miR319a, MIR319a, between species from the Brassicaceae. We compared the genomic context in Arabidopsis thaliana, Arabidopsis halleri, and Capsella rubella, using bacterial artificial chromosome clones, and analyzed precursor sequences obtained by polymerase chain reaction from 13 additional species. Phylogenetic shadowing identifies a conserved motif around the transcription start site, which we demonstrate to be functionally important. We further assessed the functionality of MIR319a orthologs from several Brassicaceae species in A. thaliana. The ortholog from kale (Brassica oleracea var. acephala) was found to be largely inactive, at least partially due to mutations in the miRNA itself, but experimental evidence suggests that loss of miR319a function is compensated by other members of the miR319 family. More broadly, we find that the foldback diverges less rapidly than the remainder of the primary transcript. To understand the molecular evolution of miRNA genes, investigations at different levels of phylogenetic divergence are required.}, } @article {pmid18296413, year = {2008}, author = {Larroux, C and Luke, GN and Koopman, P and Rokhsar, DS and Shimeld, SM and Degnan, BM}, title = {Genesis and expansion of metazoan transcription factor gene classes.}, journal = {Molecular biology and evolution}, volume = {25}, number = {5}, pages = {980-996}, doi = {10.1093/molbev/msn047}, pmid = {18296413}, issn = {1537-1719}, support = {G19873/2/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Forkhead Transcription Factors/genetics ; Fungi/genetics ; Genes, Homeobox ; Invertebrates/cytology/genetics ; Molecular Sequence Data ; POU Domain Factors/genetics ; Paired Box Transcription Factors/genetics ; Phylogeny ; Porifera/classification/cytology/*genetics ; Protein Structure, Tertiary/genetics ; Transcription Factors/*genetics ; }, abstract = {We know little about the genomic events that led to the advent of a multicellular grade of organization in animals, one of the most dramatic transitions in evolution. Metazoan multicellularity is correlated with the evolution of embryogenesis, which presumably was underpinned by a gene regulatory network reliant on the differential activation of signaling pathways and transcription factors. Many transcription factor genes that play critical roles in bilaterian development largely appear to have evolved before the divergence of cnidarian and bilaterian lineages. In contrast, sponges seem to have a more limited suite of transcription factors, suggesting that the developmental regulatory gene repertoire changed markedly during early metazoan evolution. Using whole-genome information from the sponge Amphimedon queenslandica, a range of eumetazoans, and the choanoflagellate Monosiga brevicollis, we investigate the genesis and expansion of homeobox, Sox, T-box, and Fox transcription factor genes. Comparative analyses reveal that novel transcription factor domains (such as Paired, POU, and T-box) arose very early in metazoan evolution, prior to the separation of extant metazoan phyla but after the divergence of choanoflagellate and metazoan lineages. Phylogenetic analyses indicate that transcription factor classes then gradually expanded at the base of Metazoa before the bilaterian radiation, with each class following a different evolutionary trajectory. Based on the limited number of transcription factors in the Amphimedon genome, we infer that the genome of the metazoan last common ancestor included fewer gene members in each class than are present in extant eumetazoans. Transcription factor orthologues present in sponge, cnidarian, and bilaterian genomes may represent part of the core metazoan regulatory network underlying the origin of animal development and multicellularity.}, } @article {pmid18285453, year = {2008}, author = {Déry, U and Coulombe, Y and Rodrigue, A and Stasiak, A and Richard, S and Masson, JY}, title = {A glycine-arginine domain in control of the human MRE11 DNA repair protein.}, journal = {Molecular and cellular biology}, volume = {28}, number = {9}, pages = {3058-3069}, pmid = {18285453}, issn = {1098-5549}, mesh = {Acid Anhydride Hydrolases ; Amino Acid Motifs ; Animals ; Arginine/*metabolism ; Cell Cycle Proteins/metabolism ; Cell Line ; *DNA Breaks, Double-Stranded ; *DNA Repair ; DNA Repair Enzymes/metabolism ; DNA-Binding Proteins/genetics/metabolism/*physiology ; Glycine/*metabolism ; Histones/metabolism ; Humans ; MRE11 Homologue Protein ; Methylation ; Nuclear Proteins/metabolism ; Protein Binding ; Protein-Arginine N-Methyltransferases/metabolism ; Rad51 Recombinase/metabolism ; Recombinant Proteins/metabolism ; Repressor Proteins/metabolism ; }, abstract = {Human MRE11 is a key enzyme in DNA double-strand break repair and genome stability. Human MRE11 bears a glycine-arginine-rich (GAR) motif that is conserved among multicellular eukaryotic species. We investigated how this motif influences MRE11 function. Human MRE11 alone or a complex of MRE11, RAD50, and NBS1 (MRN) was methylated in insect cells, suggesting that this modification is conserved during evolution. We demonstrate that PRMT1 interacts with MRE11 but not with the MRN complex, suggesting that MRE11 arginine methylation occurs prior to the binding of NBS1 and RAD50. Moreover, the first six methylated arginines are essential for the regulation of MRE11 DNA binding and nuclease activity. The inhibition of arginine methylation leads to a reduction in MRE11 and RAD51 focus formation on a unique double-strand break in vivo. Furthermore, the MRE11-methylated GAR domain is sufficient for its targeting to DNA damage foci and colocalization with gamma-H2AX. These studies highlight an important role for the GAR domain in regulating MRE11 function at the biochemical and cellular levels during DNA double-strand break repair.}, } @article {pmid18282717, year = {2008}, author = {Széll, M and Bata-Csörgo, Z and Kemény, L}, title = {The enigmatic world of mRNA-like ncRNAs: their role in human evolution and in human diseases.}, journal = {Seminars in cancer biology}, volume = {18}, number = {2}, pages = {141-148}, doi = {10.1016/j.semcancer.2008.01.007}, pmid = {18282717}, issn = {1096-3650}, mesh = {Animals ; *Biological Evolution ; Disease/*etiology ; *Genetic Predisposition to Disease ; Genome, Human ; Hominidae/*genetics ; Humans ; MicroRNAs/*genetics ; Psoriasis/genetics ; RNA, Untranslated/genetics/metabolism/*physiology ; Sequence Homology, Nucleic Acid ; Stress, Physiological/genetics ; }, abstract = {Accumulating data on non-protein-coding transcripts suggest that besides the regulatory machinery driven by proteins, another yet enigmatic regulatory network of RNA molecules operates and has considerable impact on cell functions. Moreover, deregulation of these non-coding RNAs (ncRNAs) has been documented in several human diseases suggesting that they may significantly contribute to their pathogenesis. This review summarizes our present knowledge on the role of the so-called mRNA-like ncRNAs in the complexity of multicellular organisms. We provide some examples to show how these mRNA-like non-coding RNAs have been discovered, how their cellular functions and role in the pathogenesis of human diseases have been revealed.}, } @article {pmid18276888, year = {2008}, author = {Abedin, M and King, N}, title = {The premetazoan ancestry of cadherins.}, journal = {Science (New York, N.Y.)}, volume = {319}, number = {5865}, pages = {946-948}, doi = {10.1126/science.1151084}, pmid = {18276888}, issn = {1095-9203}, mesh = {Actin Cytoskeleton/metabolism ; Amino Acid Sequence ; Animals ; Base Sequence ; *Biological Evolution ; Cadherins/*chemistry/*genetics/physiology ; Cell Adhesion ; Ciona intestinalis/chemistry ; Cnidaria/chemistry ; Drosophila melanogaster/chemistry ; Eukaryota/*chemistry ; Eukaryotic Cells/*chemistry/physiology ; Mice ; Molecular Sequence Data ; Protein Structure, Tertiary ; Repetitive Sequences, Amino Acid ; Signal Transduction ; Tyrosine/metabolism ; src Homology Domains ; }, abstract = {Cadherin-mediated cell adhesion and signaling is essential for metazoan development and yet is absent from all other multicellular organisms. We found cadherin genes at numbers similar to those observed in complex metazoans in one of the closest single-celled relatives of metazoans, the choanoflagellate Monosiga brevicollis. Because the evolution of metazoans from a single-celled ancestor required novel cell adhesion and signaling mechanisms, the discovery of diverse cadherins in choanoflagellates suggests that cadherins may have contributed to metazoan origins.}, } @article {pmid18275891, year = {2008}, author = {Yan, D and Olkkonen, VM}, title = {Characteristics of oxysterol binding proteins.}, journal = {International review of cytology}, volume = {265}, number = {}, pages = {253-285}, doi = {10.1016/S0074-7696(07)65007-4}, pmid = {18275891}, issn = {0074-7696}, mesh = {Animals ; Biological Transport ; Cell Membrane/chemistry/*metabolism ; Golgi Apparatus ; Humans ; Lipid Metabolism/*physiology ; Receptors, Steroid/chemistry/*metabolism ; Saccharomyces cerevisiae/metabolism ; Signal Transduction/*physiology ; Sterols/chemistry/*metabolism ; }, abstract = {Protein families characterized by a ligand binding domain related to that of oxysterol binding protein (OSBP) have been identified in eukaryotic species from yeast to humans. These proteins, designated OSBP-related (ORP) or OSBP-like (OSBPL) proteins, have been implicated in various cellular functions. However, the detailed mechanisms of their action have remained elusive. Data from our and other laboratories suggest that binding of sterol ligands may be a unifying theme. Work with Saccharomyces cerevisiae ORPs suggests a function of these proteins in the nonvesicular intracellular transport of sterols, in secretory vesicle transport from the Golgi complex, and in the establishment of cell polarity. Mammals have more ORP genes, and differential splicing substantially increases the complexity of the encoded protein family. Functional studies on mammalian ORPs point in different directions: integration of sterol and sphingomyelin metabolism, sterol transport, regulation of neutral lipid metabolism, control of the microtubule-dependent motility of endosomes/lysosomes, and regulation of signaling cascades. We envision that during evolution, the functions of ORPs have diverged from an ancestral one in sterol transport, to meet the increasing demand of the regulatory potential in multicellular organisms. Our working hypothesis is that mammalian ORPs mainly act as sterol sensors that relay information to a spectrum of different cellular processes.}, } @article {pmid18273819, year = {2008}, author = {Hoenigsberg, HF and Tíjaro, MH and Sanabria, C}, title = {From unicellularity to multicellularity - molecular speculations about early animal evolution.}, journal = {Genetics and molecular research : GMR}, volume = {7}, number = {1}, pages = {50-59}, doi = {10.4238/vol7-1gmr375}, pmid = {18273819}, issn = {1676-5680}, mesh = {Animals ; *Biological Evolution ; *Models, Genetic ; *Models, Theoretical ; *Selection, Genetic ; }, abstract = {A morphological, physiological, developmental, and genetic organization of great complexity ineluctably unfolded from relatively simple phenomena invested with enormous potential. Sometime long ago in the Protererozoic times, parasitic invasions caused lower evolutionary levels to integrate into higher-level selection. Therefore, we have a multi-level selection problem that ultimately revolves around the question of how natural selection among lower-level units acts to create higher-level units of selection, in which Darwinian competition among replicators ceases to be the foremost force. The first level relinquishes its independence for the benefit of a higher-level cooperative force that is now the criterion of fitness for the new transition in the evolutionary process.}, } @article {pmid18273011, year = {2008}, author = {King, N and Westbrook, MJ and Young, SL and Kuo, A and Abedin, M and Chapman, J and Fairclough, S and Hellsten, U and Isogai, Y and Letunic, I and Marr, M and Pincus, D and Putnam, N and Rokas, A and Wright, KJ and Zuzow, R and Dirks, W and Good, M and Goodstein, D and Lemons, D and Li, W and Lyons, JB and Morris, A and Nichols, S and Richter, DJ and Salamov, A and Sequencing, JG and Bork, P and Lim, WA and Manning, G and Miller, WT and McGinnis, W and Shapiro, H and Tjian, R and Grigoriev, IV and Rokhsar, D}, title = {The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans.}, journal = {Nature}, volume = {451}, number = {7180}, pages = {783-788}, pmid = {18273011}, issn = {1476-4687}, support = {R37 HD028315/HD/NICHD NIH HHS/United States ; R01 GM077197/GM/NIGMS NIH HHS/United States ; R01 CA058530-14/CA/NCI NIH HHS/United States ; R01 HG004164/HG/NHGRI NIH HHS/United States ; R01 HG004164-01/HG/NHGRI NIH HHS/United States ; R01 CA058530/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Adhesion ; Conserved Sequence ; Eukaryotic Cells/classification/cytology/*metabolism ; Evolution, Molecular ; Extracellular Matrix/metabolism ; Gene Expression Regulation ; Genetic Speciation ; Genome/*genetics ; Hedgehog Proteins/chemistry/genetics ; Humans ; Introns/genetics ; Phosphotyrosine/metabolism ; *Phylogeny ; Protein Structure, Tertiary/genetics ; Receptors, Notch/chemistry/genetics ; Signal Transduction/genetics ; Transcription Factors/genetics/metabolism ; Transcription, Genetic ; }, abstract = {Choanoflagellates are the closest known relatives of metazoans. To discover potential molecular mechanisms underlying the evolution of metazoan multicellularity, we sequenced and analysed the genome of the unicellular choanoflagellate Monosiga brevicollis. The genome contains approximately 9,200 intron-rich genes, including a number that encode cell adhesion and signalling protein domains that are otherwise restricted to metazoans. Here we show that the physical linkages among protein domains often differ between M. brevicollis and metazoans, suggesting that abundant domain shuffling followed the separation of the choanoflagellate and metazoan lineages. The completion of the M. brevicollis genome allows us to reconstruct with increasing resolution the genomic changes that accompanied the origin of metazoans.}, } @article {pmid18272966, year = {2008}, author = {Santorelli, LA and Thompson, CR and Villegas, E and Svetz, J and Dinh, C and Parikh, A and Sucgang, R and Kuspa, A and Strassmann, JE and Queller, DC and Shaulsky, G}, title = {Facultative cheater mutants reveal the genetic complexity of cooperation in social amoebae.}, journal = {Nature}, volume = {451}, number = {7182}, pages = {1107-1110}, doi = {10.1038/nature06558}, pmid = {18272966}, issn = {1476-4687}, support = {G0400103/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Amoeba/genetics/physiology ; Animals ; Cell Aggregation ; Chimera/genetics/physiology ; *Cooperative Behavior ; Dictyostelium/cytology/*genetics/*physiology ; Genes, Protozoan/genetics ; Genome/genetics ; Genomics ; Mutation/*genetics ; Myxococcus xanthus/genetics/physiology ; Phenotype ; *Social Behavior ; Spores, Protozoan/genetics/physiology ; }, abstract = {Cooperation is central to many major transitions in evolution, including the emergence of eukaryotic cells, multicellularity and eusociality. Cooperation can be destroyed by the spread of cheater mutants that do not cooperate but gain the benefits of cooperation from others. However, cooperation can be preserved if cheaters are facultative, cheating others but cooperating among themselves. Several cheater mutants have been studied before, but no study has attempted a genome-scale investigation of the genetic opportunities for cheating. Here we describe such a screen in a social amoeba and show that cheating is multifaceted by revealing cheater mutations in well over 100 genes of diverse types. Many of these mutants cheat facultatively, producing more than their fair share of spores in chimaeras, but cooperating normally when clonal. These findings indicate that phenotypically stable cooperative systems may nevertheless harbour genetic conflicts. The opportunities for evolutionary moves and countermoves in such conflicts may select for the involvement of multiple pathways and numerous genes.}, } @article {pmid18271627, year = {2008}, author = {Agrawal, AF and Wang, AD}, title = {Increased transmission of mutations by low-condition females: evidence for condition-dependent DNA repair.}, journal = {PLoS biology}, volume = {6}, number = {2}, pages = {e30}, pmid = {18271627}, issn = {1545-7885}, mesh = {Animals ; *DNA Repair ; Drosophila melanogaster/*genetics ; Female ; Genetic Variation ; Genomic Imprinting ; *Mutation ; X Chromosome ; }, abstract = {Evidence is mounting that mutation rates are sufficiently high for deleterious alleles to be a major evolutionary force affecting the evolution of sex, the maintenance of genetic variation, and many other evolutionary phenomena. Though point estimates of mutation rates are improving, we remain largely ignorant of the biological factors affecting these rates at the individual level. Of special importance is the possibility that mutation rates are condition-dependent with low-condition individuals experiencing more mutation. Theory predicts that such condition dependence would dramatically increase the rate at which populations adapt to new environments and the extent to which populations suffer from mutation load. Despite its importance, there has been little study of this phenomenon in multicellular organisms. Here, we examine whether DNA repair processes are condition-dependent in Drosophila melanogaster. In this species, damaged DNA in sperm can be repaired by maternal repair processes after fertilization. We exposed high- and low-condition females to sperm containing damaged DNA and then assessed the frequency of lethal mutations on paternally derived X chromosomes transmitted by these females. The rate of lethal mutations transmitted by low-condition females was 30% greater than that of high-condition females, indicating reduced repair capacity of low-condition females. A separate experiment provided no support for an alternative hypothesis based on sperm selection.}, } @article {pmid18249461, year = {2008}, author = {Tirosh, I and Barkai, N}, title = {Evolution of gene sequence and gene expression are not correlated in yeast.}, journal = {Trends in genetics : TIG}, volume = {24}, number = {3}, pages = {109-113}, doi = {10.1016/j.tig.2007.12.004}, pmid = {18249461}, issn = {0168-9525}, mesh = {*Base Sequence ; *Evolution, Molecular ; Gene Expression Regulation, Fungal/*genetics ; Saccharomyces cerevisiae/*genetics ; }, abstract = {We show that, in yeast, the divergence rate of gene expression is not correlated with that of its associated coding sequence. Gene essentiality influences both modes of evolution, but other properties related to protein structure or promoter composition are only correlated with coding-sequence divergence or gene expression divergence, respectively. Based on these findings, we discuss the possibilities of neutral evolution of gene expression and of different modes of evolution in unicellular versus multicellular organisms.}, } @article {pmid18249019, year = {2008}, author = {Mittapalli, O and Shukle, RH}, title = {Molecular characterization and responsive expression of a defender against apoptotic cell death homologue from the Hessian fly, Mayetiola destructor.}, journal = {Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology}, volume = {149}, number = {3}, pages = {517-523}, doi = {10.1016/j.cbpb.2007.12.001}, pmid = {18249019}, issn = {1096-4959}, mesh = {Amino Acid Sequence ; Animals ; *Apoptosis ; Base Sequence ; Diptera/*cytology/*genetics/growth & development ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Insect Proteins/chemistry/*genetics/metabolism ; Larva/metabolism ; Molecular Sequence Data ; Phylogeny ; RNA, Messenger/genetics/metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; Triticum/parasitology ; }, abstract = {Apoptosis or programmed cell death is an active process occurring in multicellular organisms to maintain growth and development. The Hessian fly, Mayetiola destructor, is rapidly emerging as a model insect species to study insect-plant interactions and to decipher some exceptional physiological phenomena. In this study, we report the characterization and expression profiles of a putative Hessian fly defender against apoptotic cell death (DAD1) homologue designated MdesDAD1. The deduced amino acid sequence of MdesDAD1 revealed significant similarity (75% identity, 9e-42) to other insect and non-insect DAD1 sequences. Phylogenetic analysis grouped MdesDAD1 within a sub-clade consisting of other insect DAD1 homologues. Quantitative analysis indicated constitutive levels of MdesDAD1 mRNA in all the tissues examined but an altered expression pattern during development, wherein the highest mRNA levels observed were prior to pupation. Most interestingly, MdesDAD1 transcript was found to be up-regulated during incompatible (larvae reared on resistant wheat) Hessian fly/wheat interactions compared to compatible (larvae reared on susceptible wheat) interactions. These results suggest MdesDAD1 to have a putative role in the inhibition of unwanted apoptosis triggered during development and in incompatible Hessian fly/wheat interactions. The results obtained provide clues to plausible insect and host-plant factors that could be responsible for the induction of MdesDAD1.}, } @article {pmid18245843, year = {2008}, author = {Salipante, SJ and Thompson, JM and Horwitz, MS}, title = {Phylogenetic fate mapping: theoretical and experimental studies applied to the development of mouse fibroblasts.}, journal = {Genetics}, volume = {178}, number = {2}, pages = {967-977}, pmid = {18245843}, issn = {0016-6731}, support = {R01DK078340/DK/NIDDK NIH HHS/United States ; DP1OD003278/OD/NIH HHS/United States ; R01 DK078340/DK/NIDDK NIH HHS/United States ; T32 GM007266/GM/NIGMS NIH HHS/United States ; F30 AG030316/AG/NIA NIH HHS/United States ; F30AG030316/AG/NIA NIH HHS/United States ; DP1 OD003278/OD/NIH HHS/United States ; T32GM007266/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bayes Theorem ; Caenorhabditis elegans/genetics ; Cell Division ; Computer Simulation ; DNA/genetics ; Fibroblasts/cytology/*physiology ; Mice/*classification/*genetics ; Models, Genetic ; Mutation ; *Phylogeny ; }, abstract = {Mutations are an inevitable consequence of cell division. Similarly to how DNA sequence differences allow inferring evolutionary relationships between organisms, we and others have recently demonstrated how somatic mutations may be exploited for phylogenetically reconstructing lineages of individual cells during development in multicellular organisms. However, a problem with such "phylogenetic fate maps" is that they cannot be verified experimentally; distinguishing actual lineages within clonal populations requires direct observation of cell growth, as was used to construct the fate map of Caenorhabditis elegans, but is not possible in higher organisms. Here we employ computer simulation of mitotic cell division to determine how factors such as the quantity of cells, mutation rate, and the number of examined marker sequences contribute to fidelity of phylogenetic fate maps and to explore statistical methods for assessing accuracy. To experimentally evaluate these factors, as well as for the purpose of investigating the developmental origins of connective tissue, we have produced a lineage map of fibroblasts harvested from various organs of an adult mouse. Statistical analysis demonstrates that the inferred relationships between cells in the phylogenetic fate map reflect biological information regarding the origin of fibroblasts and is suggestive of cell migration during mesenchymal development.}, } @article {pmid18236175, year = {2008}, author = {Rangan, L and Vogel, C and Srivastava, A}, title = {Analysis of context sequence surrounding translation initiation site from complete genome of model plants.}, journal = {Molecular biotechnology}, volume = {39}, number = {3}, pages = {207-213}, pmid = {18236175}, issn = {1073-6085}, mesh = {Arabidopsis/*genetics ; *Genome, Plant ; Humans ; Models, Genetic ; Oryza/*genetics ; *Protein Biosynthesis ; }, abstract = {Regions flanking the translation initiation site (TIS) are thought to play a crucial role in translation efficiency of mRNAs, but their exact sequence and evolution in eukaryotes are still a matter of debate. We investigated the context sequences in 20 nucleotides around the TIS in multi-cellular eukaryotes, with a focus on two model plants and a comparison to human. We identified consensus sequences aaaaaaa(A/G)(A/C)aAUGGcgaataata and ggcggc(g/c)(A/G)(A/C)(G/C)AUGGCggcggcgg for Arabidopsis thaliana and Oryza sativa, respectively. We observe strongly conserved G at position +4 and A or C at position -2; however, the exact nucleotide frequencies vary between the three organisms even at these conserved positions. The frequency of pyrimidines, which are considered sub optimum at position -3, is higher in both plants than in human. Arabidopsis is GC-depleted (AU-enriched) compared to both rice and human, and the enrichment is slightly stronger upstream than downstream of AUG. While both plants are similar though not identical in their variation of nucleotide frequencies, rice and human are more similar to each other than Arabidopsis and human. All three organisms display clear periodicity in A + G and C + U content when analyzing normalized frequencies. These findings suggest that, besides few highly conserved positions, overall structure of the context sequence plays a larger role in TIS recognition than the actual nucleotide frequencies.}, } @article {pmid18228266, year = {2007}, author = {Marga, F and Neagu, A and Kosztin, I and Forgacs, G}, title = {Developmental biology and tissue engineering.}, journal = {Birth defects research. Part C, Embryo today : reviews}, volume = {81}, number = {4}, pages = {320-328}, doi = {10.1002/bdrc.20109}, pmid = {18228266}, issn = {1542-9768}, mesh = {Animals ; Biophysical Phenomena ; Biophysics ; Bioreactors ; Computer Simulation ; *Developmental Biology ; Humans ; Models, Biological ; Spheroids, Cellular ; Tissue Engineering/*methods ; }, abstract = {Morphogenesis implies the controlled spatial organization of cells that gives rise to tissues and organs in early embryonic development. While morphogenesis is under strict genetic control, the formation of specialized biological structures of specific shape hinges on physical processes. Tissue engineering (TE) aims at reproducing morphogenesis in the laboratory, i.e., in vitro, to fabricate replacement organs for regenerative medicine. The classical approach to generate tissues/organs is by seeding and expanding cells in appropriately shaped biocompatible scaffolds, in the hope that the maturation process will result in the desired structure. To accomplish this goal more naturally and efficiently, we set up and implemented a novel TE method that is based on principles of developmental biology and employs bioprinting, the automated delivery of cellular composites into a three-dimensional (3D) biocompatible environment. The novel technology relies on the concept of tissue liquidity according to which multicellular aggregates composed of adhesive and motile cells behave in analogy with liquids: in particular, they fuse. We emphasize the major role played by tissue fusion in the embryo and explain how the parameters (surface tension, viscosity) that govern tissue fusion can be used both experimentally and theoretically to control and simulate the self-assembly of cellular spheroids into 3D living structures. The experimentally observed postprinting shape evolution of tube- and sheet-like constructs is presented. Computer simulations, based on a liquid model, support the idea that tissue liquidity may provide a mechanism for in vitro organ building.}, } @article {pmid18205615, year = {2007}, author = {Aleshin, VV and Konstantinova, AV and Mikhailov, KV and Nikitin, MA and Petrov, NB}, title = {Do we need many genes for phylogenetic inference?.}, journal = {Biochemistry. Biokhimiia}, volume = {72}, number = {12}, pages = {1313-1323}, doi = {10.1134/s000629790712005x}, pmid = {18205615}, issn = {0006-2979}, mesh = {Animals ; Base Sequence ; Databases, Genetic ; Eukaryotic Cells/metabolism ; Evolution, Molecular ; Expressed Sequence Tags ; Genes/*genetics ; Humans ; Models, Genetic ; *Phylogeny ; RNA, Ribosomal, 18S/genetics ; Ribosomal Proteins/genetics ; }, abstract = {Fifty-six nuclear protein coding genes from Taxonomically Broad EST Database and other databases were selected for phylogenomic-based examination of alternative phylogenetic hypotheses concerning intergroup relationship between multicellular animals (Metazoa) and other representatives of Opisthokonta. The results of this work support sister group relationship between Metazoa and Choanoflagellata. Both of these groups form the taxon Holozoa along with the monophyletic Ichthyosporea or Mesomycetozoea (a group that includes Amoebidium parasiticum, Sphaeroforma arctica, and Capsaspora owczarzaki). These phylogenetic hypotheses receive high statistical support both when utilizing whole alignment and when only 5000 randomly selected alignment positions are used. The presented results suggest subdivision of Fungi into Eumycota and lower fungi, Chytridiomycota. The latter form a monophyletic group that comprises Chytridiales+Spizellomycetales+Blastocladiales (Batrachochytrium, Spizellomyces, Allomyces, Blastocladiella), contrary to the earlier reports based on the analysis of 18S rRNA and a limited set of protein coding genes. The phylogenetic distribution of genes coding for a ubiquitin-fused ribosomal protein S30 implies at least three independent cases of gene fusion: in the ancestors of Holozoa, in heterotrophic Heterokonta (Oomycetes and Blastocystis) and in the ancestors of Cryptophyta and Glaucophyta. Ubiquitin-like sequences fused with ribosomal protein S30 outside of Holozoa are not FUBI orthologs. Two independent events of FUBI replacement by the ubiquitin sequence were detected in the lineage of C. owczarzaki and in the monophyletic group of nematode worms Tylenchomorpha+Cephalobidae. Bursaphelenchus xylophilus (Aphelenchoidoidea) retains a state typical of the rest of the Metazoa. The data emphasize the fact that the reliability of phylogenetic reconstructions depends on the number of analyzed genes to a lesser extent than on our ability to recognize reconstruction artifacts.}, } @article {pmid18202867, year = {2005}, author = {Rosslenbroich, B}, title = {The evolution of multicellularity in animals as a shift in biological autonomy.}, journal = {Theory in biosciences = Theorie in den Biowissenschaften}, volume = {123}, number = {3}, pages = {243-262}, pmid = {18202867}, issn = {1431-7613}, abstract = {The hypothesis is advanced that major evolutionary innovations are characterized by an increase of organismal autonomy in the sense of an emancipation from the environment. After a brief overview of the literature on this concept, increasing autonomy is defined as the evolutionary shift in the individual system-environment relationship, so that the direct influences of the environment are gradually reduced and a stabilization of self-referential, intrinsic functions within the system is generated. This is described as relative autonomy because numerous interconnections with the environment and dependencies upon it are retained. Elements of an increasing autonomy are spatial separations, an increase in homeostatic functions, internalizations and an increase in physiological and behavioral flexibility. These elements are described by taking the transition from single cells to metazoans as a case study. The principle of increasing autonomy is of central relevance for understanding this transition. The hypothesis does not contradict the principle of adaptation, but rather contributes to a further understanding of its elements as it supplies aspects for a reconsideration of the relationship between the outside and the inside, between organism and environment.}, } @article {pmid18202389, year = {2008}, author = {Anderson, JA and Song, YS and Langley, CH}, title = {Molecular population genetics of Drosophila subtelomeric DNA.}, journal = {Genetics}, volume = {178}, number = {1}, pages = {477-487}, pmid = {18202389}, issn = {0016-6731}, support = {K99 GM080099/GM/NIGMS NIH HHS/United States ; R01 HG002942/HG/NHGRI NIH HHS/United States ; R01-HG002942/HG/NHGRI NIH HHS/United States ; 1K99-GM080099/GM/NIGMS NIH HHS/United States ; }, mesh = {Africa ; Animals ; Chromosomes/genetics ; Crossing Over, Genetic ; DNA/*genetics ; Drosophila melanogaster/classification/*genetics ; Molecular Sequence Data ; North America ; Polymorphism, Single Nucleotide/genetics ; Population Dynamics ; Telomere/*genetics ; }, abstract = {DNA sequence surveys in yeast and humans suggest that the forces shaping telomeric polymorphism and divergence are distinctly more dynamic than those in the euchromatic, gene-rich regions of the chromosomes. However, the generality of this pattern across outbreeding, multicellular eukaryotes has not been determined. To characterize the structure and evolution of Drosophila telomeres, we collected and analyzed molecular population genetics data from the X chromosome subtelomere in 58 lines of North American Drosophila melanogaster and 29 lines of African D. melanogaster. We found that Drosophila subtelomeres exhibit high levels of both structural and substitutional polymorphism relative to linked euchromatic regions. We also observed strikingly different patterns of variation in the North American and African samples. Moreover, our analyses of the polymorphism data identify a localized hotspot of recombination in the most-distal portion of the X subtelomere. While the levels of polymorphism decline sharply and in parallel with rates of crossing over per physical length over the distal first euchromatic megabase pairs of the X chromosome, our data suggest that they rise again sharply in the subtelomeric region (approximately 80 kbp). These patterns of historical recombination and geographic differentiation indicate that, similar to yeast and humans, Drosophila subtelomeric DNA is evolving very differently from euchromatic DNA.}, } @article {pmid18184723, year = {2008}, author = {Ruiz-Trillo, I and Roger, AJ and Burger, G and Gray, MW and Lang, BF}, title = {A phylogenomic investigation into the origin of metazoa.}, journal = {Molecular biology and evolution}, volume = {25}, number = {4}, pages = {664-672}, doi = {10.1093/molbev/msn006}, pmid = {18184723}, issn = {1537-1719}, mesh = {Animals ; Eukaryota/classification/*genetics ; *Evolution, Molecular ; *Genome ; Mitochondrial Proteins/chemistry/genetics ; *Phylogeny ; Protein Structure, Tertiary ; Protozoan Proteins/chemistry ; }, abstract = {The evolution of multicellular animals (Metazoa) from their unicellular ancestors was a key transition that was accompanied by the emergence and diversification of gene families associated with multicellularity. To clarify the timing and order of specific events in this transition, we conducted expressed sequence tag surveys on 4 putative protistan relatives of Metazoa including the choanoflagellate Monosiga ovata, the ichthyosporeans Sphaeroforma arctica and Amoebidium parasiticum, and the amoeba Capsaspora owczarzaki, and 2 members of Amoebozoa, Acanthamoeba castellanii and Mastigamoeba balamuthi. We find that homologs of genes involved in metazoan multicellularity exist in several of these unicellular organisms, including 1 encoding a membrane-associated guanylate kinase with an inverted arrangement of protein-protein interaction domains (MAGI) in Capsaspora. In Metazoa, MAGI regulates tight junctions involved in cell-cell communication. By phylogenomic analyses of genes encoded in nuclear and mitochondrial genomes, we show that the choanoflagellates are the closest relatives of the Metazoa, followed by the Capsaspora and Ichthyosporea lineages, although the branching order between the latter 2 groups remains unclear. Understanding the function of "metazoan-specific" proteins we have identified in these protists will clarify the evolutionary steps that led to the emergence of the Metazoa.}, } @article {pmid18181960, year = {2008}, author = {Charrier, B and Coelho, SM and Le Bail, A and Tonon, T and Michel, G and Potin, P and Kloareg, B and Boyen, C and Peters, AF and Cock, JM}, title = {Development and physiology of the brown alga Ectocarpus siliculosus: two centuries of research.}, journal = {The New phytologist}, volume = {177}, number = {2}, pages = {319-332}, doi = {10.1111/j.1469-8137.2007.02304.x}, pmid = {18181960}, issn = {0028-646X}, mesh = {Biological Evolution ; Ecology ; Ecosystem ; Genome, Plant ; Phaeophyta/classification/genetics/*growth & development/*physiology ; }, abstract = {Brown algae share several important features with land plants, such as their photoautotrophic nature and their cellulose-containing wall, but the two groups are distantly related from an evolutionary point of view. The heterokont phylum, to which the brown algae belong, is a eukaryotic crown group that is phylogenetically distinct not only from the green lineage, but also from the red algae and the opisthokont phylum (fungi and animals). As a result of this independent evolutionary history, the brown algae exhibit many novel features and, moreover, have evolved complex multicellular development independently of the other major groups already mentioned. In 2004, a consortium of laboratories, including the Station Biologique in Roscoff and Genoscope, initiated a project to sequence the genome of Ectocarpus siliculosus, a small filamentous brown alga that is found in temperate, coastal environments throughout the globe. The E. siliculosus genome, which is currently being annotated, is expected to be the first completely characterized genome of a multicellular alga. In this review we look back over two centuries of work on this brown alga and highlight the advances that have led to the choice of E. siliculosus as a genomic and genetic model organism for the brown algae.}, } @article {pmid18178563, year = {2008}, author = {Froquet, R and Cherix, N and Birke, R and Benghezal, M and Cameroni, E and Letourneur, F and Mösch, HU and De Virgilio, C and Cosson, P}, title = {Control of cellular physiology by TM9 proteins in yeast and Dictyostelium.}, journal = {The Journal of biological chemistry}, volume = {283}, number = {11}, pages = {6764-6772}, doi = {10.1074/jbc.M704484200}, pmid = {18178563}, issn = {0021-9258}, mesh = {Animals ; Autophagy ; Cell Adhesion ; Dictyostelium/*metabolism ; Fungal Proteins/genetics/*metabolism/*physiology ; *Gene Expression Regulation ; *Gene Expression Regulation, Fungal ; Lysosomes/metabolism ; Membrane Proteins/genetics/*physiology ; Models, Biological ; Mutation ; Plasmids/metabolism ; Saccharomyces cerevisiae/metabolism ; Signal Transduction ; Species Specificity ; }, abstract = {TM9 proteins constitute a well defined family, characterized by the presence of a large variable extracellular domain and nine putative transmembrane domains. This family is highly conserved throughout evolution and comprises three members in Dictyostelium discoideum and Saccharomyces cerevisiae and four in humans and mice. In Dictyostelium, previous analysis demonstrated that TM9 proteins are implicated in cellular adhesion. In this study, we generated TM9 mutants in S. cerevisiae and analyzed their phenotype with particular attention to cellular adhesion. S. cerevisiae strains lacking any one of the three TM9 proteins were severely suppressed for adhesive growth and filamentous growth under conditions of nitrogen starvation. In these mutants, expression of the FLO11-lacZ reporter gene was strongly reduced, whereas expression of FRE(Ty1)-lacZ was not, suggesting that TM9 proteins are implicated at a late stage of nutrient-controlled signaling pathways. We also reexamined the phenotype of Dictyostelium TM9 mutant cells, focusing on nutrient-controlled cellular functions. Although the initiation of multicellular development and autophagy was unaltered in Dictyostelium TM9 mutants, nutrient-controlled secretion of lysosomal enzymes was dysregulated in these cells. These results suggest that in both yeast and amoebae, TM9 proteins participate in the control of specific cellular functions in response to changing nutrient conditions.}, } @article {pmid19579709, year = {2008}, author = {Reynolds, A and Hülsmann, N}, title = {Ernst Haeckel's discovery of Magosphaera planula: a vestige of metazoan origins?.}, journal = {History and philosophy of the life sciences}, volume = {30}, number = {3-4}, pages = {339-386}, pmid = {19579709}, issn = {0391-9714}, mesh = {Animals ; *Biological Evolution ; Eukaryota ; Germany ; History, 19th Century ; Humans ; Metaphysics/*history ; Models, Biological ; Norway ; Phylogeny ; Zoology/*history ; }, abstract = {In September of 1869, while studying sponges off the Norwegian island of Gisoe, Ernst Haeckel (1834-1919) discovered a tiny, flagellated ball-shaped organism swimming about in his samples. Appearing first to be the planula larva of an invertebrate marine animal further observation revealed it to be a colony of flagellated cells with a complex life cycle transitioning between multicellular and single-cell stages and several distinct forms of protozoa. Haeckel named it Magosphaera planula (the "magician's ball") and it eventually assumed a central role in his theories of animal evolution, appearing as the modern exemplar of the blastaea stage in his gastraea theory of metazoan evolution. Throughout the latter half of the nineteenth century and into the twentieth it was an object of considerable scientific interest, and yet it was only ever observed by Haeckel himself and then only the once. Eventually it faded altogether from scientific discussion. This paper traces the rise and fall of Magosphaera as an important epistemic object in the theories of Haeckel and other biologists, and an attempt is made to identify what exactly the organism (or organisms!) was that Haeckel observed in the fall of 1869.}, } @article {pmid18162580, year = {2008}, author = {Yi, S and Sahni, N and Daniels, KJ and Pujol, C and Srikantha, T and Soll, DR}, title = {The same receptor, G protein, and mitogen-activated protein kinase pathway activate different downstream regulators in the alternative white and opaque pheromone responses of Candida albicans.}, journal = {Molecular biology of the cell}, volume = {19}, number = {3}, pages = {957-970}, pmid = {18162580}, issn = {1939-4586}, support = {AI-2392/AI/NIAID NIH HHS/United States ; }, mesh = {Biofilms/drug effects ; Biomarkers/metabolism ; Candida albicans/*cytology/*enzymology/genetics/physiology ; Fungal Proteins/genetics/metabolism ; GTP-Binding Proteins/*metabolism ; Gene Expression Regulation, Fungal/drug effects ; Genes, Switch ; Mitogen-Activated Protein Kinases/*metabolism ; Models, Biological ; Mutation/genetics ; Phenotype ; Pheromones/*pharmacology ; Receptors, Pheromone/*metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {Candida albicans must undergo a switch from white to opaque to mate. Opaque cells then release mating type-specific pheromones that induce mating responses in opaque cells. Uniquely in C. albicans, the same pheromones induce mating-incompetent white cells to become cohesive, form an adhesive basal layer of cells on a surface, and then generate a thicker biofilm that, in vitro, facilitates mating between minority opaque cells. Through mutant analysis, it is demonstrated that the pathways regulating the white and opaque cell responses to the same pheromone share the same upstream components, including receptors, heterotrimeric G protein, and mitogen-activated protein kinase cascade, but they use different downstream transcription factors that regulate the expression of genes specific to the alternative responses. This configuration, although common in higher, multicellular systems, is not common in fungi, and it has not been reported in Saccharomyces cerevisiae. The implications in the evolution of multicellularity in higher eukaryotes are discussed.}, } @article {pmid18162537, year = {2008}, author = {Helman, Y and Natale, F and Sherrell, RM and Lavigne, M and Starovoytov, V and Gorbunov, MY and Falkowski, PG}, title = {Extracellular matrix production and calcium carbonate precipitation by coral cells in vitro.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {1}, pages = {54-58}, pmid = {18162537}, issn = {1091-6490}, mesh = {Agglutinins/chemistry ; Animals ; Anthozoa ; Calcification, Physiologic ; Calcium Carbonate/*chemistry/metabolism ; Cell Survival ; Cells, Cultured ; Collagen/chemistry ; Colorimetry/methods ; DNA, Ribosomal/chemistry ; Extracellular Matrix/*metabolism ; Extracellular Matrix Proteins/chemistry ; In Vitro Techniques ; Lectins/chemistry ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence/methods ; Models, Biological ; RNA, Ribosomal, 18S/chemistry ; Triticum/metabolism ; }, abstract = {The evolution of multicellularity in animals required the production of extracellular matrices that serve to spatially organize cells according to function. In corals, three matrices are involved in spatial organization: (i) an organic ECM, which facilitates cell-cell and cell-substrate adhesion; (ii) a skeletal organic matrix (SOM), which facilitates controlled deposition of a calcium carbonate skeleton; and (iii) the calcium carbonate skeleton itself, which provides the structural support for the 3D organization of coral colonies. In this report, we examine the production of these three matrices by using an in vitro culturing system for coral cells. In this system, which significantly facilitates studies of coral cell physiology, we demonstrate in vitro excretion of ECM by primary (nondividing) tissue cultures of both soft (Xenia elongata) and hard (Montipora digitata) corals. There are structural differences between the ECM produced by X. elongata cell cultures and that of M. digitata, and ascorbic acid, a critical cofactor for proline hydroxylation, significantly increased the production of collagen in the ECM of the latter species. We further demonstrate in vitro production of SOM and extracellular mineralized particles in cell cultures of M. digitata. Inductively coupled plasma mass spectrometry analysis of Sr/Ca ratios revealed the particles to be aragonite. De novo calcification was confirmed by following the incorporation of (45)Ca into acid labile macromolecules. Our results demonstrate the ability of isolated, differentiated coral cells to undergo fundamental processes required for multicellular organization.}, } @article {pmid18157077, year = {2007}, author = {Sanchez, S and Hourdez, S and Lallier, FH}, title = {[Chemoautotrophic endosymbioses: contemporary models for symbiogenesis?].}, journal = {Journal de la Societe de biologie}, volume = {201}, number = {3}, pages = {247-257}, doi = {10.1051/jbio:2007036}, pmid = {18157077}, issn = {1295-0661}, mesh = {Animals ; Biological Evolution ; Cyanobacteria/physiology ; Earth, Planet ; Eukaryotic Cells/physiology ; Geography ; Models, Biological ; Photosynthesis ; Symbiosis/*physiology ; Time ; }, abstract = {Oxygen appears to be one of the key factors in understanding the evolution of life on Earth. Almost absent during more than 2 billion years, its subsequent increase is correlated with the emergence of oxygenic photosynthesis by Cyanobacteria, followed by aerobic Prokaryotes and eventually Eukaryotes, all primitively aerobic, and more recently, the development of complex multicellular organisms. However, in some reduced environments, still present at the surface of the Earth and even more so in ocean depths (hydrothermal vents, cold seeps, massive organic falls,...), anaerobic or micro-aerobic Prokaryotes continue to grow, including some chemoautotrophic bacteria deriving energy from sulfide oxidation for instance. A few Metazoa have managed to collaborate with such chemoautotroph Prokaryotes, the most abundant species forming endosymbiotic associations. The most studied of these endosymbioses (the mussels Bathymodiolus, the vestimentiferan tubeworm Riftia pachyptila, or the clams Calyptogena) have revealed important differences in the degree of interdependence between host and symbionts, and in the mode of symbiont transmission. The evolutive process of these symbioses is reminiscent of the primary endosymbioses which have given rise to the organelles of heterotrophic Eukaryotes (mitochondria) and phototrophic Eukaryotes (chloroplasts). The study of these modern days biological models could shed light on symbiogenesis itself and also potentially reveal thiotrophic Eukaryotes as a new lineage.}, } @article {pmid18086378, year = {2007}, author = {Shenoy, AR and Kim, BH and Choi, HP and Matsuzawa, T and Tiwari, S and MacMicking, JD}, title = {Emerging themes in IFN-gamma-induced macrophage immunity by the p47 and p65 GTPase families.}, journal = {Immunobiology}, volume = {212}, number = {9-10}, pages = {771-784}, pmid = {18086378}, issn = {0171-2985}, support = {R01 AI068041/AI/NIAID NIH HHS/United States ; R01 AI068041-01A1/AI/NIAID NIH HHS/United States ; R01 AI068041-02/AI/NIAID NIH HHS/United States ; R01 AI068041-03/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; GTP Phosphohydrolases/chemistry/genetics/*metabolism ; GTP-Binding Proteins/chemistry/genetics/*metabolism ; Humans ; Immunity, Active ; *Immunity, Innate ; Interferon-gamma/*immunology ; Macrophages/enzymology/*immunology/metabolism ; Phylogeny ; Transcription Factors/immunology/*metabolism ; }, abstract = {Vertebrates have evolved complex immune specificity repertoires beyond the primordial components found in lower multi-cellular organisms to combat microbial infections. The type II interferon (IFN-gamma) pathway represents one such system, bridging innate and acquired immunity and providing host protection in a cell-autonomous manner. Recent large-scale transcriptome analyses of IFN-gamma-dependent gene expression in effector cells such as macrophages have highlighted the prominence of two families of GTPases -- p47 IRGs and p65 GBPs -- that are now beginning to emerge as major determinants of antimicrobial resistance. Here we discuss the recent clarification of known family members, their cellular biochemistry and host defense functions as a means to understanding the complex innate immune response engendered in higher vertebrates such as humans and mice.}, } @article {pmid18085819, year = {2007}, author = {Pepper, JW and Sprouffske, K and Maley, CC}, title = {Animal cell differentiation patterns suppress somatic evolution.}, journal = {PLoS computational biology}, volume = {3}, number = {12}, pages = {e250}, pmid = {18085819}, issn = {1553-7358}, support = {K01 CA089267/CA/NCI NIH HHS/United States ; K01 CA89267/CA/NCI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Cell Communication/*physiology ; Cell Differentiation/*physiology ; Cell Division/*physiology ; *Cell Proliferation ; Cell Size ; Cell Survival/*physiology ; Computer Simulation ; *Models, Biological ; }, abstract = {Cell differentiation in multicellular organisms has the obvious function during development of creating new cell types. However, in long-lived organisms with extensive cell turnover, cell differentiation often continues after new cell types are no longer needed or produced. Here, we address the question of why this is true. It is believed that multicellular organisms could not have arisen or been evolutionarily stable without possessing mechanisms to suppress somatic selection among cells within organisms, which would otherwise disrupt organismal integrity. Here, we propose that one such mechanism is a specific pattern of ongoing cell differentiation commonly found in metazoans with cell turnover, which we call "serial differentiation." This pattern involves a sequence of differentiation stages, starting with self-renewing somatic stem cells and proceeding through several (non-self-renewing) transient amplifying cell stages before ending with terminally differentiated cells. To test the hypothesis that serial differentiation can suppress somatic evolution, we used an agent-based computer simulation of cell population dynamics and evolution within tissues. The results indicate that, relative to other, simpler patterns, tissues organized into serial differentiation experience lower rates of detrimental cell-level evolution. Self-renewing cell populations are susceptible to somatic evolution, while those that are not self-renewing are not. We find that a mutation disrupting differentiation can create a new self-renewing cell population that is vulnerable to somatic evolution. These results are relevant not only to understanding the evolutionary origins of multicellularity, but also the causes of pathologies such as cancer and senescence in extant metazoans, including humans.}, } @article {pmid18079367, year = {2008}, author = {Rensing, SA and Lang, D and Zimmer, AD and Terry, A and Salamov, A and Shapiro, H and Nishiyama, T and Perroud, PF and Lindquist, EA and Kamisugi, Y and Tanahashi, T and Sakakibara, K and Fujita, T and Oishi, K and Shin-I, T and Kuroki, Y and Toyoda, A and Suzuki, Y and Hashimoto, S and Yamaguchi, K and Sugano, S and Kohara, Y and Fujiyama, A and Anterola, A and Aoki, S and Ashton, N and Barbazuk, WB and Barker, E and Bennetzen, JL and Blankenship, R and Cho, SH and Dutcher, SK and Estelle, M and Fawcett, JA and Gundlach, H and Hanada, K and Heyl, A and Hicks, KA and Hughes, J and Lohr, M and Mayer, K and Melkozernov, A and Murata, T and Nelson, DR and Pils, B and Prigge, M and Reiss, B and Renner, T and Rombauts, S and Rushton, PJ and Sanderfoot, A and Schween, G and Shiu, SH and Stueber, K and Theodoulou, FL and Tu, H and Van de Peer, Y and Verrier, PJ and Waters, E and Wood, A and Yang, L and Cove, D and Cuming, AC and Hasebe, M and Lucas, S and Mishler, BD and Reski, R and Grigoriev, IV and Quatrano, RS and Boore, JL}, title = {The Physcomitrella genome reveals evolutionary insights into the conquest of land by plants.}, journal = {Science (New York, N.Y.)}, volume = {319}, number = {5859}, pages = {64-69}, doi = {10.1126/science.1150646}, pmid = {18079367}, issn = {1095-9203}, support = {BBS/E/C/00004948/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adaptation, Physiological ; Animals ; Arabidopsis/genetics/physiology ; *Biological Evolution ; Bryopsida/*genetics/physiology ; Chlamydomonas reinhardtii/genetics/physiology ; Computational Biology ; DNA Repair ; Dehydration ; Gene Duplication ; Genes, Plant ; *Genome, Plant ; Magnoliopsida/genetics/physiology ; Metabolic Networks and Pathways/genetics ; Multigene Family ; Oryza/genetics/physiology ; Phylogeny ; Plant Proteins/genetics/physiology ; Repetitive Sequences, Nucleic Acid ; Retroelements ; Sequence Analysis, DNA ; Signal Transduction/genetics ; }, abstract = {We report the draft genome sequence of the model moss Physcomitrella patens and compare its features with those of flowering plants, from which it is separated by more than 400 million years, and unicellular aquatic algae. This comparison reveals genomic changes concomitant with the evolutionary movement to land, including a general increase in gene family complexity; loss of genes associated with aquatic environments (e.g., flagellar arms); acquisition of genes for tolerating terrestrial stresses (e.g., variation in temperature and water availability); and the development of the auxin and abscisic acid signaling pathways for coordinating multicellular growth and dehydration response. The Physcomitrella genome provides a resource for phylogenetic inferences about gene function and for experimental analysis of plant processes through this plant's unique facility for reverse genetics.}, } @article {pmid18073380, year = {2008}, author = {Nikoh, N and Tanaka, K and Shibata, F and Kondo, N and Hizume, M and Shimada, M and Fukatsu, T}, title = {Wolbachia genome integrated in an insect chromosome: evolution and fate of laterally transferred endosymbiont genes.}, journal = {Genome research}, volume = {18}, number = {2}, pages = {272-280}, pmid = {18073380}, issn = {1088-9051}, mesh = {Animals ; Base Sequence ; Blotting, Southern ; Chromosome Mapping ; Chromosomes/*genetics ; Coleoptera/genetics/*microbiology ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Genome/*genetics ; In Situ Hybridization, Fluorescence ; Likelihood Functions ; Models, Genetic ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Pseudogenes/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; *Symbiosis ; Wolbachia/*genetics ; }, abstract = {Recent accumulation of microbial genome data has demonstrated that lateral gene transfers constitute an important and universal evolutionary process in prokaryotes, while those in multicellular eukaryotes are still regarded as unusual, except for endosymbiotic gene transfers from mitochondria and plastids. Here we thoroughly investigated the bacterial genes derived from a Wolbachia endosymbiont on the nuclear genome of the beetle Callosobruchus chinensis. Exhaustive PCR detection and Southern blot analysis suggested that approximately 30% of Wolbachia genes, in terms of the gene repertoire of wMel, are present on the insect nuclear genome. Fluorescent in situ hybridization located the transferred genes on the proximal region of the basal short arm of the X chromosome. Molecular evolutionary and other lines of evidence indicated that the transferred genes are probably derived from a single lateral transfer event. The transferred genes were, for the length examined, structurally disrupted, freed from functional constraints, and transcriptionally inactive. Hence, most, if not all, of the transferred genes have been pseudogenized. Notwithstanding this, the transferred genes were ubiquitously detected from Japanese and Taiwanese populations of C. chinensis, while the number of the transferred genes detected differed between the populations. The transferred genes were not detected from congenic beetle species, indicating that the transfer event occurred after speciation of C. chinensis, which was estimated to be one or several million years ago. These features of the laterally transferred endosymbiont genes are compared with the evolutionary patterns of mitochondrial and plastid genome fragments acquired by nuclear genomes through recent endosymbiotic gene transfers.}, } @article {pmid18070109, year = {2008}, author = {Liu, Q}, title = {Identification of rice TUBBY-like genes and their evolution.}, journal = {The FEBS journal}, volume = {275}, number = {1}, pages = {163-171}, doi = {10.1111/j.1742-4658.2007.06186.x}, pmid = {18070109}, issn = {1742-464X}, mesh = {*Evolution, Molecular ; *Genes, Plant ; Genetic Variation ; Oryza/*genetics ; Phylogeny ; }, abstract = {The identification of TUBBY-like genes in organisms ranging from single-celled to multicellular eukaryotes has allowed the phylogenetic history of this gene family to be traced back to the early evolutionary stages of eukaryote development. Rice TUBBY-like genes were located on chromosomes 1, 2, 3, 4, 5, 7, 8, 11 and 12 without any obvious clustering. On a genomic scale, it was revealed that the rice TUBBY-like gene family probably evolved mainly through segmental duplication produced by polyploidy. The altered selective constraints (or site-specific rate changes), related to functional divergence during protein evolution between plant and animal TUBBY-like genes, were statistically significant. Based on posterior probability analysis, five amino acid sites (103, 312, 315, 317 and 319) are thought to be responsible for functional divergence.}, } @article {pmid18060440, year = {2008}, author = {Roberts, TH and Hejgaard, J}, title = {Serpins in plants and green algae.}, journal = {Functional & integrative genomics}, volume = {8}, number = {1}, pages = {1-27}, pmid = {18060440}, issn = {1438-793X}, mesh = {Amino Acid Sequence ; Chlorophyta/genetics/*metabolism ; Molecular Sequence Data ; Phylogeny ; Plants/genetics/*metabolism ; Serine Proteinase Inhibitors/metabolism ; Serpins/chemistry/genetics/*metabolism ; Terminology as Topic ; }, abstract = {Control of proteolysis is important for plant growth, development, responses to stress, and defence against insects and pathogens. Members of the serpin protein family are likely to play a critical role in this control through irreversible inhibition of endogenous and exogenous target proteinases. Serpins have been found in diverse species of the plant kingdom and represent a distinct clade among serpins in multicellular organisms. Serpins are also found in green algae, but the evolutionary relationship between these serpins and those of plants remains unknown. Plant serpins are potent inhibitors of mammalian serine proteinases of the chymotrypsin family in vitro but, intriguingly, plants and green algae lack endogenous members of this proteinase family, the most common targets for animal serpins. An Arabidopsis serpin with a conserved reactive centre is now known to be capable of inhibiting an endogenous cysteine proteinase. Here, knowledge of plant serpins in terms of sequence diversity, inhibitory specificity, gene expression and function is reviewed. This was advanced through a phylogenetic analysis of amino acid sequences of expressed plant serpins, delineation of plant serpin gene structures and prediction of inhibitory specificities based on identification of reactive centres. The review is intended to encourage elucidation of plant serpin functions.}, } @article {pmid18058370, year = {2007}, author = {Friedrich, J and Ebner, R and Kunz-Schughart, LA}, title = {Experimental anti-tumor therapy in 3-D: spheroids--old hat or new challenge?.}, journal = {International journal of radiation biology}, volume = {83}, number = {11-12}, pages = {849-871}, doi = {10.1080/09553000701727531}, pmid = {18058370}, issn = {0955-3002}, mesh = {Antineoplastic Agents/*pharmacology ; Bioreactors ; Cell Culture Techniques/methods ; Cell Line, Tumor/*drug effects/*pathology ; Coculture Techniques ; Drug Screening Assays, Antitumor ; Female ; Humans ; Male ; Models, Biological ; Spheroids, Cellular/*drug effects/*pathology/physiology ; }, abstract = {PURPOSE: To give a state-of-the-art overview on the promise of three-dimensional (3-D) culture systems for anticancer drug development, with particular emphasis on multicellular tumor spheroids (MCTS).

RESULTS AND CONCLUSIONS: Cell-based assays have become an integral component in many stages of routine anti-tumor drug testing. However, they are almost always based on homogenous monolayer or suspension cultures and thus represent a rather artificial cellular environment. 3-D cultures--such as the well established spheroid culture system--better reflect the in vivo behavior of cells in tumor tissues and are increasingly recognized as valuable advanced tools for evaluating the efficacy of therapeutic intervention. The present article summarizes past and current applications and particularly discusses technological challenges, required improvements and recent progress with the use of the spheroid model in experimental therapeutics, as a basis for sophisticated drug/therapy screening. A brief overview is given focusing on the nomenclature of spherical 3-D cultures, their potential to mimic many aspects of the pathophysiological situation in tumors, and currently available protocols for culturing and analysis. A list of spheroid-forming epithelial cancer cell lines of different origin is provided and the recent trend to use spheroids for testing combination treatment strategies is highlighted. Finally, various spheroid co-culture approaches are presented that have been established to study heterologous cell interactions in solid tumors and thereby are able to reflect the cellular tumor environment with increasing accuracy. The intriguing observation that in order to retain certain tumor initiating cell properties, some primary tumor cell populations must be maintained exclusively in 3-D culture is mentioned, adding a new but fascinating challenge for future therapeutic campaigns.}, } @article {pmid18058146, year = {2007}, author = {Zhu, S}, title = {Evidence for myxobacterial origin of eukaryotic defensins.}, journal = {Immunogenetics}, volume = {59}, number = {12}, pages = {949-954}, pmid = {18058146}, issn = {0093-7711}, mesh = {Amino Acid Sequence ; Animals ; Computational Biology ; Cysteine/chemistry ; Defensins/*chemistry/*genetics ; Eukaryotic Cells/*physiology ; Evolution, Molecular ; Models, Molecular ; Molecular Sequence Data ; Myxococcales/*chemistry/metabolism ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid ; }, abstract = {Antimicrobial defensins with the cysteine-stabilized alpha-helical and beta-sheet (CS alpha beta) motif are a large family of ancient, evolutionarily related innate immunity effectors of multicellular organisms. Although the widespread distribution in plants, fungi, and invertebrates suggests their uniqueness to Eukarya, it is unknown whether these eukaryotic defensins originated before or posterior to the emergence of eukaryotes. In this study, we provide evidence in support of the existence of defensin-like peptides (DLPs) in myxobacteria based on structural bioinformatics analysis, which recognized two bacterial peptides with a conserved cysteine-stabilized alpha-helical motif, a nested structural unit of the CS alpha beta motif. Similarity in sequence and structure to fungal DLPs together with restricted distribution to the myxobacteria as well as central role of the myxobacteria in the origin of eukaryotes suggest that the bacterial DLPs represent the ancestor of the eukaryotic defensins and could mediate immune defense of early eukaryotes after gene transfer to the proto-eukaryotic genome. Our work thus offers a basis for further investigation of prokaryotic origin of eukaryotic immune effector molecules.}, } @article {pmid18053938, year = {2007}, author = {Cleland, CE}, title = {Epistemological issues in the study of microbial life: alternative terran biospheres?.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {38}, number = {4}, pages = {847-861}, doi = {10.1016/j.shpsc.2007.09.007}, pmid = {18053938}, issn = {1369-8486}, mesh = {*Earth, Planet ; Evolution, Molecular ; *Exobiology ; Gene Transfer, Horizontal ; *Genetics, Microbial ; Humans ; *Knowledge ; *Life ; Meteoroids ; *Molecular Biology ; Nucleic Acids ; *Origin of Life ; Planets ; Polymerase Chain Reaction ; }, abstract = {The assumption that all life on Earth today shares the same basic molecular architecture and biochemistry is part of the paradigm of modern biology. This paper argues that there is little theoretical or empirical support for this widely held assumption. Scientists know that life could have been at least modestly different at the molecular level and it is clear that alternative molecular building blocks for life were available on the early Earth. If the emergence of life is, like other natural phenomena, highly probable given the right chemical and physical conditions then it seems likely that the early Earth hosted multiple origins of life, some of which produced chemical variations on life as we know it. While these points are often conceded, it is nevertheless maintained that any primitive alternatives to familiar life would have been eliminated long ago, either amalgamated into a single form of life through lateral gene transfer (LGT) or alternatively out-competed by our putatively more evolutionarily robust form of life. Besides, the argument continues, if such life forms still existed, we surely would have encountered telling signs of them by now. These arguments do not hold up well under close scrutiny. They reflect a host of assumptions that are grounded in our experience with large multicellular organisms and, most importantly, do not apply to microbial forms of life, which cannot be easily studied without the aid of sophisticated technologies. Significantly, the most powerful molecular biology techniques available-polymerase chain reaction (PCR) amplification of rRNA genes augmented by metagenomic analysis-could not detect such microbes if they existed. Given the profound philosophical and scientific importance that such a discovery would represent, a dedicated search for 'shadow microbes' (heretofore unrecognized 'alien' forms of terran microbial life) seems in order. The best place to start such a search is with puzzling (anomalous) phenomena, such as desert varnish, that resist classification as 'biological' or 'nonbiological'.}, } @article {pmid18053935, year = {2007}, author = {Shapiro, JA}, title = {Bacteria are small but not stupid: cognition, natural genetic engineering and socio-bacteriology.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {38}, number = {4}, pages = {807-819}, doi = {10.1016/j.shpsc.2007.09.010}, pmid = {18053935}, issn = {1369-8486}, mesh = {*Bacteria/genetics ; Bacterial Physiological Phenomena ; Bacteriology/*history ; *Biological Evolution ; *Cognition ; Colony Count, Microbial ; Cybernetics ; DNA ; DNA Transposable Elements ; *Genetic Engineering ; History, 20th Century ; History, 21st Century ; Humans ; *Selection, Genetic ; Signal Transduction ; Species Specificity ; }, abstract = {Forty years' experience as a bacterial geneticist has taught me that bacteria possess many cognitive, computational and evolutionary capabilities unimaginable in the first six decades of the twentieth century. Analysis of cellular processes such as metabolism, regulation of protein synthesis, and DNA repair established that bacteria continually monitor their external and internal environments and compute functional outputs based on information provided by their sensory apparatus. Studies of genetic recombination, lysogeny, antibiotic resistance and my own work on transposable elements revealed multiple widespread bacterial systems for mobilizing and engineering DNA molecules. Examination of colony development and organization led me to appreciate how extensive multicellular collaboration is among the majority of bacterial species. Contemporary research in many laboratories on cell-cell signaling, symbiosis and pathogenesis show that bacteria utilise sophisticated mechanisms for intercellular communication and even have the ability to commandeer the basic cell biology of 'higher' plants and animals to meet their own needs. This remarkable series of observations requires us to revise basic ideas about biological information processing and recognise that even the smallest cells are sentient beings.}, } @article {pmid18053736, year = {2008}, author = {Bedhomme, M and Jouannic, S and Champion, A and Simanis, V and Henry, Y}, title = {Plants, MEN and SIN.}, journal = {Plant physiology and biochemistry : PPB}, volume = {46}, number = {1}, pages = {1-10}, doi = {10.1016/j.plaphy.2007.10.010}, pmid = {18053736}, issn = {0981-9428}, mesh = {Arabidopsis/*physiology ; Arabidopsis Proteins/genetics/metabolism ; Cell Cycle Proteins/genetics/metabolism ; Cytokinesis/*physiology ; *Evolution, Molecular ; Gene Expression Regulation, Plant/*physiology ; Mitosis/*physiology ; Monomeric GTP-Binding Proteins/genetics/metabolism ; Protein Kinases/genetics/metabolism ; Schizosaccharomyces/physiology ; Schizosaccharomyces pombe Proteins/genetics/metabolism ; Signal Transduction/*physiology ; Transcription, Genetic/physiology ; }, abstract = {In fission yeast, the onset of septation is signalled through the septum initiation network (SIN) signaling pathway. Similarly, in budding yeast the onset of budding is signalled through the mitotic exit network (MEN) pathway. We previously characterized in Arabidopsis signaling elements (GTPases, kinases) closely related to the core elements (spg1p/TEM1p, cdc7p/CDC15p) of the SIN and MEN pathways. Our first results suggested that a plant signaling pathway must be used to coordinate mitotic exit with cytokinesis. This review questioned the value of such an hypothesis in a multicellular organism. The core elements (G-protein, kinase) of the SIN and MEN pathways were only detected in fungi, plants and Mycetozoa. We also noticed that AtSGP GTPase and AtMAP3Kepsilon kinase revealed two paralogues in Arabidopsis. Although Arabidopsis genes complement fission yeast mutants, and Arabidopsis proteins interact with fission yeast proteins, plants do not use these core elements to coordinate the termination of cell division with cytokinesis. Transcriptional regulation and expression data suggest a function for the plant SIN-like elements in the control of cell type specification. Exploring the evolutionary conservation of an ancient signaling pathway provides evidence that evolution has recycled regulatory elements for elaborating a new signaling avenue.}, } @article {pmid18048290, year = {2008}, author = {Lessells, CK}, title = {Neuroendocrine control of life histories: what do we need to know to understand the evolution of phenotypic plasticity?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {363}, number = {1497}, pages = {1589-1598}, pmid = {18048290}, issn = {0962-8436}, mesh = {*Biological Evolution ; *Environment ; *Models, Biological ; Neurosecretory Systems/*physiology ; *Phenotype ; Reproduction/*physiology ; }, abstract = {Almost all life histories are phenotypically plastic: that is, life-history traits such as timing of breeding, family size or the investment in individual offspring vary with some aspect of the environment, such as temperature or food availability. One approach to understanding this phenotypic plasticity from an evolutionary point of view is to extend the optimality approach to the range of environments experienced by the organism. This approach attempts to understand the value of particular traits in terms of the selection pressures that act on them either directly or owing to trade-offs due to resource allocation and other factors such as predation risk. Because these selection pressures will between environments, the predicted optimal phenotype will too. The relationship expressing the optimal phenotype for different environments is the optimal reaction norm and describes the optimal phenotypic plasticity. However, this view of phenotypic plasticity ignores the fact that the reaction norm must be underlain by some sort of control system: cues about the environment must be collected by sense organs, integrated into a decision about the appropriate life history, and a message sent to the relevant organs to implement that decision. In multicellular animals, this control mechanism is the neuroendocrine system. The central question that this paper addresses is whether the control system affects the reaction norm that evolves. This might happen in two different ways: first, the control system will create constraints on the evolution of reaction norms if it cannot be configured to produce the optimal reaction norm and second, the control system will create additional selection pressures on reaction norms if the neuroendocrine system is costly. If either of these happens, a full understanding of the way in which selection shapes reaction norms must include details of the neuroendocrine control system. This paper presents the conceptual framework needed to explain what is meant by a constraint or cost being created by the neuroendocrine system and discusses the extent to which this occurs and some possible examples. The purpose of doing this is to encourage endocrinologists to take a fresh look at neuroendocrine mechanisms and help identify the properties of the system and situations in which these generate constraints and costs that impinge on the evolution of phenotypic plasticity.}, } @article {pmid18036158, year = {2008}, author = {Willensdorfer, M}, title = {Organism size promotes the evolution of specialized cells in multicellular digital organisms.}, journal = {Journal of evolutionary biology}, volume = {21}, number = {1}, pages = {104-110}, pmid = {18036158}, issn = {1420-9101}, support = {R01 GM078986/GM/NIGMS NIH HHS/United States ; R01 GM078986-02/GM/NIGMS NIH HHS/United States ; R01GM078986/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; *Body Size ; *Computer Simulation ; *Models, Biological ; }, abstract = {Specialized cells are the essence of complex multicellular life. Fossils allow us to study the modification of specialized, multicellular features such as jaws, scales, and muscular appendages. But it is still unclear what organismal properties contributed to the transition from undifferentiated organisms, which contain only a single cell type, to multicellular organisms with specialized cells. Using digital organisms I studied this transition. My simulations show that the transition to specialized cells happens faster in organism composed of many cells than in organisms composed of few cells. Large organisms suffer less from temporarily unsuccessful evolutionary experiments with individual cells, allowing them to evolve specialized cells via evolutionary trajectories that are unavailable to smaller organisms. This demonstrates that the evolution of simple multicellular organisms which are composed of many functionally identical cells accelerates the evolution of more complex organisms with specialized cells.}, } @article {pmid18031303, year = {2008}, author = {Herron, MD and Michod, RE}, title = {Evolution of complexity in the volvocine algae: transitions in individuality through Darwin's eye.}, journal = {Evolution; international journal of organic evolution}, volume = {62}, number = {2}, pages = {436-451}, doi = {10.1111/j.1558-5646.2007.00304.x}, pmid = {18031303}, issn = {0014-3820}, mesh = {Animals ; Bayes Theorem ; *Biological Evolution ; Cell Differentiation ; Cell Division ; Chlamydomonas/*genetics ; Codon ; Eukaryota/*genetics/metabolism ; *Evolution, Molecular ; Models, Biological ; Models, Genetic ; Models, Theoretical ; Monte Carlo Method ; Phylogeny ; Volvox/*genetics ; }, abstract = {The transition from unicellular to differentiated multicellular organisms constitutes an increase in the level complexity, because previously existing individuals are combined to form a new, higher-level individual. The volvocine algae represent a unique opportunity to study this transition because they diverged relatively recently from unicellular relatives and because extant species display a range of intermediate grades between unicellular and multicellular, with functional specialization of cells. Following the approach Darwin used to understand "organs of extreme perfection" such as the vertebrate eye, this jump in complexity can be reduced to a series of small steps that cumulatively describe a gradual transition between the two levels. We use phylogenetic reconstructions of ancestral character states to trace the evolution of steps involved in this transition in volvocine algae. The history of these characters includes several well-supported instances of multiple origins and reversals. The inferred changes can be understood as components of cooperation-conflict-conflict mediation cycles as predicted by multilevel selection theory. One such cycle may have taken place early in volvocine evolution, leading to the highly integrated colonies seen in extant volvocine algae. A second cycle, in which the defection of somatic cells must be prevented, may still be in progress.}, } @article {pmid18031242, year = {2007}, author = {Tapping, RI and Omueti, KO and Johnson, CM}, title = {Genetic polymorphisms within the human Toll-like receptor 2 subfamily.}, journal = {Biochemical Society transactions}, volume = {35}, number = {Pt 6}, pages = {1445-1448}, doi = {10.1042/BST0351445}, pmid = {18031242}, issn = {0300-5127}, mesh = {Humans ; *Polymorphism, Genetic ; Toll-Like Receptor 1/genetics/immunology ; Toll-Like Receptor 10/genetics/immunology ; Toll-Like Receptor 2/*genetics/immunology ; Toll-Like Receptor 6/genetics/immunology ; }, abstract = {Infectious disease is a formidable selective force in Nature as is evident from the complexity of immune systems across multicellular species. TLRs (Toll-like receptors) constitute central pattern-recognition molecules of the innate immune system that sense bacterial, viral, fungal, protozoan and helminth organisms and activate responses that provide immediate as well as long-term protection for the host. The present article reviews the function and evolution of vertebrate TLRs with an emphasis on the subfamily of receptors comprising human TLR1, 2, 6 and 10. The idea that TLRs undergo strong purifying selection provides the framework for the discussion of single nucleotide polymorphisms, many of which are associated with the incidence of infectious disease.}, } @article {pmid18027391, year = {2007}, author = {Bhattacharya, D and Archibald, JM and Weber, AP and Reyes-Prieto, A}, title = {How do endosymbionts become organelles? Understanding early events in plastid evolution.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {29}, number = {12}, pages = {1239-1246}, doi = {10.1002/bies.20671}, pmid = {18027391}, issn = {0265-9247}, mesh = {*Biological Evolution ; Models, Biological ; Plant Proteins/chemistry ; Plastids/*physiology ; Protein Transport ; *Symbiosis ; }, abstract = {What factors drove the transformation of the cyanobacterial progenitor of plastids (e.g. chloroplasts) from endosymbiont to bona fide organelle? This question lies at the heart of organelle genesis because, whereas intracellular endosymbionts are widespread in both unicellular and multicellular eukaryotes (e.g. rhizobial bacteria, Chlorella cells in ciliates, Buchnera in aphids), only two canonical eukaryotic organelles of endosymbiotic origin are recognized, the plastids of algae and plants and the mitochondrion. Emerging data on (1) the discovery of non-canonical plastid protein targeting, (2) the recent origin of a cyanobacterial-derived organelle in the filose amoeba Paulinella chromatophora, and (3) the extraordinarily reduced genomes of psyllid bacterial endosymbionts begin to blur the distinction between endosymbiont and organelle. Here we discuss the use of these terms in light of new data in order to highlight the unique aspects of plastids and mitochondria and underscore their central role in eukaryotic evolution.}, } @article {pmid18024428, year = {2008}, author = {Ben-Dov, C and Hartmann, B and Lundgren, J and Valcárcel, J}, title = {Genome-wide analysis of alternative pre-mRNA splicing.}, journal = {The Journal of biological chemistry}, volume = {283}, number = {3}, pages = {1229-1233}, doi = {10.1074/jbc.R700033200}, pmid = {18024428}, issn = {0021-9258}, mesh = {Alternative Splicing/*genetics ; Animals ; Disease ; Genome, Human/*genetics ; Humans ; RNA Precursors/*genetics ; }, abstract = {Alternative splicing of mRNA precursors allows the synthesis of multiple mRNAs from a single primary transcript, significantly expanding the information content and regulatory possibilities of higher eukaryotic genomes. High-throughput enabling technologies, particularly large-scale sequencing and splicing-sensitive microarrays, are providing unprecedented opportunities to address key questions in this field. The picture emerging from these pioneering studies is that alternative splicing affects most human genes and a significant fraction of the genes in other multicellular organisms, with the potential to greatly influence the evolution of complex genomes. A combinatorial code of regulatory signals and factors can deploy physiologically coherent programs of alternative splicing that are distinct from those regulated at other steps of gene expression. Pre-mRNA splicing and its regulation play important roles in human pathologies, and genome-wide analyses in this area are paving the way for improved diagnostic tools and for the identification of novel and more specific pharmaceutical targets.}, } @article {pmid18023738, year = {2008}, author = {Flenner, E and Marga, F and Neagu, A and Kosztin, I and Forgacs, G}, title = {Relating biophysical properties across scales.}, journal = {Current topics in developmental biology}, volume = {81}, number = {}, pages = {461-483}, doi = {10.1016/S0070-2153(07)81016-7}, pmid = {18023738}, issn = {0070-2153}, mesh = {Animals ; Biophysical Phenomena ; *Biophysics ; Cell Aggregation ; Computer Simulation ; *Models, Biological ; Monte Carlo Method ; Morphogenesis/*physiology ; Systems Biology ; }, abstract = {A distinguishing feature of a multicellular living system is that it operates at various scales, from the intracellular to organismal. Genes and molecules set up the conditions for the physical processes to act, in particular to shape the embryo. As development continues the changes brought about by the physical processes lead to changes in gene expression. It is this coordinated interplay between genetic and generic (i.e., physical and chemical) processes that constitutes the modern understanding of early morphogenesis. It is natural to assume that in this multiscale process the smaller defines the larger. In case of biophysical properties, in particular, those at the subcellular level are expected to give rise to those at the tissue level and beyond. Indeed, the physical properties of tissues vary greatly from the liquid to solid. Very little is known at present on how tissue level properties are related to cell and subcellular properties. Modern measurement techniques provide quantitative results at both the intracellular and tissue level, but not on the connection between these. In the present work we outline a framework to address this connection. We specifically concentrate on the morphogenetic process of tissue fusion, by following the coalescence of two contiguous multicellular aggregates. The time evolution of this process can accurately be described by the theory of viscous liquids. We also study fusion by Monte Carlo simulations and a novel Cellular Particle Dynamics (CPD) model, which is similar to the earlier introduced Subcellular Element Model (SEM; Newman, 2005). Using the combination of experiments, theory and modeling we are able to relate the measured tissue level biophysical quantities to subcellular parameters. Our approach has validity beyond the particular morphogenetic process considered here and provides a general way to relate biophysical properties across scales.}, } @article {pmid18005684, year = {2007}, author = {Miller, SI and Hoffman, LR and Sanowar, S}, title = {Did bacterial sensing of host environments evolve from sensing within microbial communities?.}, journal = {Cell host & microbe}, volume = {1}, number = {2}, pages = {85-87}, doi = {10.1016/j.chom.2007.04.002}, pmid = {18005684}, issn = {1934-6069}, mesh = {Bacteria/pathogenicity ; *Bacterial Physiological Phenomena ; Biological Evolution ; *Environment ; Heme/physiology ; Staphylococcus aureus/pathogenicity ; Virulence ; }, abstract = {Bacteria sense and respond to their environment, enabling adaptation to diverse niches, including multicellular eukaryotes. In this issue of Cell Host & Microbe, Torres et al. describe how the bacterium Staphylococcus aureus responds to heme as a molecular marker of the mammalian host environment. It is likely that mechanisms for sensing such markers evolved from systems that recognized cues present in microbial communities before the emergence of eukaryotes.}, } @article {pmid17998541, year = {2007}, author = {Declerck, N and Bouillaut, L and Chaix, D and Rugani, N and Slamti, L and Hoh, F and Lereclus, D and Arold, ST}, title = {Structure of PlcR: Insights into virulence regulation and evolution of quorum sensing in Gram-positive bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {104}, number = {47}, pages = {18490-18495}, pmid = {17998541}, issn = {1091-6490}, mesh = {Bacterial Proteins/*chemistry/classification/genetics/*metabolism ; Crystallography, X-Ray ; *Evolution, Molecular ; Gram-Positive Bacteria/chemistry/genetics/*metabolism/*pathogenicity ; Models, Molecular ; Protein Binding ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; *Quorum Sensing ; Structural Homology, Protein ; Trans-Activators/*chemistry/classification/genetics/*metabolism ; Virulence ; }, abstract = {Gram-positive bacteria use a wealth of extracellular signaling peptides, so-called autoinducers, to regulate gene expression according to population densities. These "quorum sensing" systems control vital processes such as virulence, sporulation, and gene transfer. Using x-ray analysis, we determined the structure of PlcR, the major virulence regulator of the Bacillus cereus group, and obtained mechanistic insights into the effects of autoinducer binding. Our structural and phylogenetic analysis further suggests that all of those quorum sensors that bind directly to their autoinducer peptide derive from a common ancestor and form a single family (the RNPP family, for Rap/NprR/PlcR/PrgX) with conserved features. As a consequence, fundamentally different processes in different bacterial genera appear regulated by essentially the same autoinducer recognition mechanism. Our results shed light on virulence control by PlcR and elucidate origin and evolution of multicellular behavior in bacteria.}, } @article {pmid17993569, year = {2008}, author = {Etxebeste, O and Ni, M and Garzia, A and Kwon, NJ and Fischer, R and Yu, JH and Espeso, EA and Ugalde, U}, title = {Basic-zipper-type transcription factor FlbB controls asexual development in Aspergillus nidulans.}, journal = {Eukaryotic cell}, volume = {7}, number = {1}, pages = {38-48}, pmid = {17993569}, issn = {1535-9786}, mesh = {Amino Acid Sequence ; Aspergillus nidulans/genetics/*growth & development/metabolism ; Basic-Leucine Zipper Transcription Factors/genetics/*metabolism ; Cell Nucleus ; Cloning, Molecular ; DNA, Fungal/genetics/metabolism ; Fungal Proteins/genetics/*metabolism ; *Gene Expression Regulation, Fungal ; Hyphae ; Molecular Sequence Data ; Mutation/genetics ; Phenotype ; Phylogeny ; RNA, Fungal/genetics/metabolism ; Reproduction, Asexual/*physiology ; Sequence Homology, Amino Acid ; Spores, Fungal/physiology ; Transcriptional Activation ; }, abstract = {The fungal colony is a complex multicellular unit consisting of various cell types and functions. Asexual spore formation (conidiation) is integrated through sensory and regulatory elements into the general morphogenetic plan, in which the activation of the transcription factor BrlA is the first determining step. A number of early regulatory elements acting upstream of BrlA (fluG and flbA-E) have been identified, but their functional relations remain to be further investigated. In this report we describe FlbB as a putative basic-zipper-type transcription factor restricted to filamentous fungi. FlbB accumulates at the hyphal apex during early vegetative growth but is later found in apical nuclei, suggesting that an activating modification triggers nuclear import. Moreover, proper temporal and quantitative expression of FlbB is a prerequisite for brlA transcription, and misscheduled overexpression inhibits conidiation. We also present evidence that FlbB activation results in the production of a second diffusible signal, acting downstream from the FluG factor, to induce conidiation.}, } @article {pmid17983575, year = {2007}, author = {Bordenstein, SR}, title = {Evolutionary genomics: transdomain gene transfers.}, journal = {Current biology : CB}, volume = {17}, number = {21}, pages = {R935-6}, doi = {10.1016/j.cub.2007.09.022}, pmid = {17983575}, issn = {0960-9822}, mesh = {Animals ; Arthropods/*genetics/*microbiology ; Evolution, Molecular ; *Gene Transfer, Horizontal ; Genes, Bacterial ; Genomics ; Nematoda/*genetics/*microbiology ; Wolbachia/*genetics ; }, abstract = {Biologists have until now conceded that bacterial gene transfer to multicellular animals is relatively uncommon in Nature. A new study showing promiscuous insertions of bacterial endosymbiont genes into invertebrate genomes ushers in a shift in this paradigm.}, } @article {pmid17983426, year = {2008}, author = {Zhang, Z and Fauser, U and Schluesener, HJ}, title = {Early attenuation of lesional interleukin-16 up-regulation by dexamethasone and FTY720 in experimental traumatic brain injury.}, journal = {Neuropathology and applied neurobiology}, volume = {34}, number = {3}, pages = {330-339}, doi = {10.1111/j.1365-2990.2007.00893.x}, pmid = {17983426}, issn = {1365-2990}, mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Brain Injuries/*metabolism/pathology/physiopathology ; Dexamethasone/*pharmacology ; Fingolimod Hydrochloride ; Functional Laterality ; Immunohistochemistry ; Interleukin-16/*biosynthesis ; Macrophages/metabolism ; Propylene Glycols/*pharmacology ; Rats ; Sphingosine/*analogs & derivatives/pharmacology ; Up-Regulation ; }, abstract = {AIMS: Interleukin-16 (IL16) is an immunomodulatory cytokine, which induces lymphocyte migration, expression of proinflammatory IL1 beta, IL6 and tumour necrosis factor-alpha, and modulates apoptosis. IL16 expression has been observed in several central nervous system diseases and may play a role in promoting inflammatory responses. Inflammation contributes considerably to secondary injury following traumatic brain injury (TBI). The aim of this study was to investigate early IL16 expression following experimental TBI and the effects of dexamethasone and FTY720 on early expression of IL16 in TBI rats.

METHODS: Rat TBI was induced using an open-skull weight-drop model. IL16 expression was studied by immunohistochemistry. TBI rats received an intraperitoneal injection of dexamethasone (1 mg/kg in 1 ml saline), FTY720 (1 mg/kg in 1 ml saline) or saline (1 ml) on Day 0 and Day 2 immediately after surgery.

RESULTS: Significant up-regulation of IL16 was seen as early as 24 h post TBI. Double-staining experiments, together with morphological classification, revealed a multicellular origin of IL16, including activated microglia/macrophages (about 85%), astrocytes (about 8%), neurones (about 5%) and granulocytes. Following peripheral administration of dexamethasone and FTY720, attenuated numbers of IL16(+) cells were observed on Days 1 and 2 but not on Day 4 post TBI for dexamethasone and on Day 4 but not earlier for FTY720 respectively.

CONCLUSIONS: Our observations reveal that dexamethasone and FTY720 have different but complementary effects on reduction of early IL16 expression following TBI.}, } @article {pmid17979704, year = {2007}, author = {Rosner, A and Rinkevich, B}, title = {The DDX3 subfamily of the DEAD box helicases: divergent roles as unveiled by studying different organisms and in vitro assays.}, journal = {Current medicinal chemistry}, volume = {14}, number = {23}, pages = {2517-2525}, doi = {10.2174/092986707782023677}, pmid = {17979704}, issn = {0929-8673}, mesh = {Animals ; Cell Cycle ; DEAD-box RNA Helicases/*chemistry/*physiology ; Drug Design ; Genome, Human ; HIV Infections/metabolism ; Hepatitis B/*metabolism ; Hepatitis C/metabolism ; Humans ; Mice ; Models, Biological ; Phylogeny ; RNA Helicases/metabolism ; RNA Splicing ; Schizosaccharomyces/metabolism ; }, abstract = {DDX3 (or Ded1p), the highly conserved subfamily of the DEAD-box RNA helicase family (40 members in humans), plays important roles in RNA metabolism. DDX3X and DDX3Y, the two human paralogous genes of this subfamily of proteins, have orthologous candidates in a diverse range of eukaryotes, from yeast and plants to animals. While DDX3Y, which is essential for normal spermatogenesis, is translated only in the testes, DDX3X protein is ubiquitously expressed, involved in RNA transcription, RNA splicing, mRNA transport, translation initiation and cell cycle regulation. Studies of recent years have revealed that DDX3X participates in HIV and hepatitis C viral infections, and in hepatocellular carcinoma, a complication of hepatitis B and hepatitis C infections. In the urochordates (i.e., Botryllus schlosseri) and in diverse invertebrate phyla (represented by model organisms such as: Drosophila, Hydra, Planaria), DDX3 proteins (termed also PL10) are involved in developmental pathways, highly expressed in adult undifferentiated soma and germ cells and in some adult and embryo's differentiating tissues. As the mechanistic and functional knowledge of DDX3 proteins is limited, we suggest assembling the available data on DDX3 proteins, from all studied organisms and in vitro assays, depicting a unified mechanistic scheme for DDX3 proteins' functions. Understanding the diverse functions of DDX3 in multicellular organisms may be particularly important for effective strategies of drug design.}, } @article {pmid17977464, year = {2007}, author = {Bornens, M and Azimzadeh, J}, title = {Origin and evolution of the centrosome.}, journal = {Advances in experimental medicine and biology}, volume = {607}, number = {}, pages = {119-129}, doi = {10.1007/978-0-387-74021-8_10}, pmid = {17977464}, issn = {0065-2598}, mesh = {Animals ; Cell Nucleus/metabolism ; Centrosome/*metabolism ; Eukaryotic Cells/metabolism ; *Evolution, Molecular ; Humans ; Models, Biological ; Phylogeny ; }, abstract = {In this brief account we specifically address the question of how the plasma membrane-associated basal body/axoneme of the unicellular ancestor of eukaryotes has evolved into the centrosome organelle through the several attempts to multicellularity. We propose that the connection between the flagellar apparatus and the nucleus has been a critical feature for leading to the centriole-based centrosome of metazoa, the Spindle Pole Body of fungi, or to the absence of any centrosome in seed plants. We further suggest that the evolution of this connection could be reflected in the evolution of the centrin proteins. We then review evidence showing that the evolution of the centrosome-based tubulin network has been correlated with the evolution of the cortical actin-based cleavage apparatus. Finally we argue that this coevolution had a major impact on the cell individuation process and on the evolution of multicellular organisms. We conclude that only the metazoan lineage evolved multicellularity without loosing the ancestral association of three basic cellular functions of the basal body/axoneme or the derived centrosome organelle, namely sensation, motion and division.}, } @article {pmid17977460, year = {2007}, author = {Gurkan, C and Koulov, AV and Balch, WE}, title = {An evolutionary perspective on eukaryotic membrane trafficking.}, journal = {Advances in experimental medicine and biology}, volume = {607}, number = {}, pages = {73-83}, doi = {10.1007/978-0-387-74021-8_6}, pmid = {17977460}, issn = {0065-2598}, support = {GM33301/GM/NIGMS NIH HHS/United States ; GM42336/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Biological Transport ; Cell Membrane/*metabolism ; Conserved Sequence ; Eukaryotic Cells/*cytology/*metabolism ; *Evolution, Molecular ; Gene Expression Profiling ; Humans ; Intracellular Membranes/*metabolism ; Membrane Fusion ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Transport ; SNARE Proteins/metabolism ; Sequence Homology, Amino Acid ; rab GTP-Binding Proteins/chemistry/genetics/metabolism ; }, abstract = {The eukaryotic cell is defined by a complex set of sub-cellular compartments that include endomembrane systems making up the exocytic and endocytic trafficking pathways. Current evidence suggests that both the function and communication between these compartments are regulated by distinct families of proteins that direct membrane fission, targeting and fusion. These families include coat protein complexes (CPCs) involved in vesicle formation/fission, Rab GTPases involved in vesicle targeting, and soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNAREs) involved in vesicle fusion. The origins of these gene families and their individual contributions to the evolutionary specialization of the membrane architectures of lower and higher eukaryotes are now better understood with the advent of powerful phylogenetic, structural and systems biology tools. Herein, we provide a perspective that suggests that while the core CPC and SNARE machineries have diversified modestly in the course of eukaryotic evolution, the Rab GTPase family expanded substantially to emerge as a key driving force in endomembrane specialization. The Rab GTPases appear to have provided the foundation for the intricate membrane architectures ranging from those requisite for the distinct amoebic life cycle stage of uni-cellular organisms such as the parasitic protozoa to the highly specialized tissue and cell type-specific endomembranes of multi-cellular eukaryotes. We propose that Rab-centric interaction networks orchestrate the divergent activities of fission and fusion through their capacity to control the sequential assembly of protein complexes that mediate endomembrane structure and communication.}, } @article {pmid17977455, year = {2007}, author = {Javaux, EJ}, title = {The early eukaryotic fossil record.}, journal = {Advances in experimental medicine and biology}, volume = {607}, number = {}, pages = {1-19}, doi = {10.1007/978-0-387-74021-8_1}, pmid = {17977455}, issn = {0065-2598}, mesh = {Eukaryotic Cells/classification/*cytology/ultrastructure ; *Evolution, Molecular ; *Fossils ; Time Factors ; }, abstract = {The Precambrian era records the evolution of the domain Eucarya. Although the taxonomy of fossils is often impossible to resolve beyond the level of domain, their morphology and chemistry indicate the evolution of major biological innovations. The late Archean record for eukaryotes is limited to trace amounts of biomarkers. Morphological evidence appears in late Paleoproterozoic and early Mesoproterozoic (1800-1300 Ma) rocks. The moderate diversity of preservable eukaryotic organisms includes cell walls without surface ornament (but with complex ultrastructure), with regularly distributed surface ornamentation, and with irregularly or regularly arranged processes. Collectively, these fossils suggest that eukaryotes with flexible membranes and cytoskeletons existed in mid-Proterozoic oceans. The late Mesoproterozoic-early Neoproterozoic (1300-750 Ma) is a time of diversification and evolution when direct evidence for important biological innovations occurs in the fossil record such as multicellularity, sex, photosynthesis, biomineralization, predation, and heterotrophy. Members of extant clades can be recognized and include bangiophyte red algae, xanthophyte algae, cladophorale green algae, euglyphid, lobose, and filose amoebae and possible fungi. In the late Neoproterozoic, besides more diversification of ornamented fossils, florideophyte red algae and brown algae diversify, and animals take the stage. The record of biological innovations documented by the fossils shows that eukaryotes had evolved most cytological and molecular complexities very early in the Proterozoic but environmental conditions delayed their diversification within clades until oxygen level and predation pressure increased significantly.}, } @article {pmid17976716, year = {2008}, author = {Kim, Y and Powell, EN and Wade, TL and Presley, BJ}, title = {Relationship of parasites and pathologies to contaminant body burden in sentinel bivalves: NOAA Status and Trends 'Mussel Watch' Program.}, journal = {Marine environmental research}, volume = {65}, number = {2}, pages = {101-127}, doi = {10.1016/j.marenvres.2007.09.003}, pmid = {17976716}, issn = {0141-1136}, mesh = {Analysis of Variance ; Animals ; Bivalvia/*drug effects/*parasitology ; Databases, Factual ; *Environmental Monitoring ; Hydrocarbons/*toxicity ; Parasites/*drug effects/isolation & purification/pathogenicity ; Principal Component Analysis ; Sentinel Surveillance ; Water Pollutants, Chemical/*toxicity ; }, abstract = {The 1995-1998 database from NOAA's National Status and Trends 'Mussel Watch' Program was used to compare the distributional patterns of parasites and pathologies with contaminant body burdens. Principal components analysis (PCA) resolved five groups of contaminants in both mussels and oysters: one dominated by polycyclic aromatic hydrocarbons (PAHs), one dominated by pesticides, and three dominated by metals. Metals produced a much more complex picture of spatial trends in body burden than did either the pesticides or PAHs. Contrasted to the relative simplicity of the contaminant groupings, PCA exposed a suite of parasite/pathology groups with few similarities between the sentinel bivalve taxa. Thus, the relationship between parasites/pathologies and contaminants differs significantly between taxa despite the similarity in contaminant pattern. Moreover, the combined effects of many contaminants and parasites may be important, leading to complex biological-contaminant interactions with synergies both of biological and chemical origin. Overall, correlations between parasites/pathologies and contaminants were more frequent with metals, frequent with pesticides, and less frequent with PAHs in mussels. In oysters, correlations with pesticides and metals were about equally frequent, but correlations with PAHs were still rare. In mytilids, correlations with metals predominated. Negative and positive correlations with metals occurred with about the same frequency in both taxa. The majority of correlations with pesticides were negative in oysters; not so for mytilids. Of the many significant correlations involving parasites, few involved single-celled eukaryotes or prokaryotes. The vast majority involved multi-cellular eukaryotes and nearly all of them either cestodes, trematode sporocysts, or trematode metacercariae. The few correlations for single-celled parasites all involved proliferating protozoa or protozoa reaching high body burdens through transmission. The tendency for the larger or more numerous parasites to be involved suggests that unequal sequestration of contaminates between host and parasite tissue is a potential mediator. An alternative is that contaminants differentially affect parasites and their hosts by varying host susceptibility or parasite survival.}, } @article {pmid17973655, year = {2008}, author = {Pereira-Leal, JB}, title = {The Ypt/Rab family and the evolution of trafficking in fungi.}, journal = {Traffic (Copenhagen, Denmark)}, volume = {9}, number = {1}, pages = {27-38}, doi = {10.1111/j.1600-0854.2007.00667.x}, pmid = {17973655}, issn = {1398-9219}, mesh = {Evolution, Molecular ; Fungal Proteins/genetics/*metabolism ; Fungi/classification/*metabolism ; Genome, Fungal ; Phylogeny ; Protein Transport ; rab GTP-Binding Proteins/genetics/*metabolism ; }, abstract = {The evolution of the eukaryotic endomembrane system and the transport pathways of their vesicular intermediates are poorly understood. A common set of organelles and pathways seems to be present in all free-living eukaryotes, but different branches of the tree of life have a variety of diverse, specialized organelles. Rab/Ypt proteins are small guanosine triphosphatases with tissue-specific and organelle-specific localization that emerged as markers for organelle diversity. Here, I characterize the Rab/Ypt family in the kingdom Fungi, a sister kingdom of Animals. I identify and annotate these proteins in 26 genomes representing near one billion years of evolution, multiple lifestyles and cellular types. Surprisingly, the minimal set of Rab/Ypt present in fungi is similar to, perhaps smaller than, the predicted eukaryotic ancestral set. This suggests that the saprophytic fungal lifestyle, multicellularity as well as the highly polarized secretion associated with hyphal growth did not require any major innovation in the molecular machinery that regulates protein trafficking. The Rab/Ypt and other protein traffic-related families are kept small, not paralleling increases in genome size, in contrast to the expansion of such components observed in other branches of the tree of life, such as the animal and plant kingdoms. This analysis suggests that multicellularity and cellular diversity in fungi followed different routes from those followed by plants and metazoa.}, } @article {pmid17971776, year = {2008}, author = {Curto, M and McClatchey, AI}, title = {Nf2/Merlin: a coordinator of receptor signalling and intercellular contact.}, journal = {British journal of cancer}, volume = {98}, number = {2}, pages = {256-262}, pmid = {17971776}, issn = {0007-0920}, mesh = {Actin Cytoskeleton/physiology ; Animals ; Cell Communication/*genetics ; Cell Membrane/physiology ; Cytoskeleton/physiology ; ErbB Receptors/metabolism/*physiology ; Evolution, Molecular ; Humans ; Models, Biological ; Neurofibromin 2/genetics/*physiology ; Signal Transduction/genetics ; }, abstract = {This review explores possible mechanisms by which the neurofibromatosis type-2 tumour suppressor Merlin regulates contact-dependent inhibition of proliferation. Starting from an evolutionary perspective, the concurrent emergence of intercellular contacts and proliferation control in multicellular organisms is first considered. Following a brief survey of the molecular and subcellular milieus in which merlin performs its function, the importance of different cellular and biological contexts in defining the function of merlin is discussed. Finally, an integrated model for merlin and the Ezrin, Radixin, and Moesin (ERM) proteins functioning in the regulation of cellular interfaces is proposed.}, } @article {pmid17951519, year = {2007}, author = {Yoshino, R and Morio, T and Yamada, Y and Kuwayama, H and Sameshima, M and Tanaka, Y and Sesaki, H and Iijima, M}, title = {Regulation of ammonia homeostasis by the ammonium transporter AmtA in Dictyostelium discoideum.}, journal = {Eukaryotic cell}, volume = {6}, number = {12}, pages = {2419-2428}, pmid = {17951519}, issn = {1535-9786}, mesh = {Ammonia/*metabolism ; Animals ; Biological Transport ; Cation Transport Proteins/genetics/*metabolism/*physiology ; Cell Communication ; *Gene Expression Regulation ; Homeostasis ; Models, Biological ; Nucleic Acids/chemistry ; Phosphorylation ; Phylogeny ; Quaternary Ammonium Compounds/*chemistry ; Signal Transduction ; }, abstract = {Ammonia has been shown to function as a morphogen at multiple steps during the development of the cellular slime mold Dictyostelium discoideum; however, it is largely unknown how intracellular ammonia levels are controlled. In the Dictyostelium genome, there are five genes that encode putative ammonium transporters: amtA, amtB, amtC, rhgA, and rhgB. Here, we show that AmtA regulates ammonia homeostasis during growth and development. We found that cells lacking amtA had increased levels of ammonia/ammonium, whereas their extracellular ammonia/ammonium levels were highly decreased. These results suggest that AmtA mediates the excretion of ammonium. In support of a role for AmtA in ammonia homeostasis, AmtA mRNA is expressed throughout the life cycle, and its expression level increases during development. Importantly, AmtA-mediated ammonia homeostasis is critical for many developmental processes. amtA(-) cells are more sensitive to NH(4)Cl than wild-type cells in inhibition of chemotaxis toward cyclic AMP and of formation of multicellular aggregates. Furthermore, even in the absence of exogenously added ammonia, we found that amtA(-) cells produced many small fruiting bodies and that the viability and germination of amtA(-) spores were dramatically compromised. Taken together, our data clearly demonstrate that AmtA regulates ammonia homeostasis and plays important roles in multiple developmental processes in Dictyostelium.}, } @article {pmid17947307, year = {2008}, author = {Koch, LG and Britton, SL}, title = {Aerobic metabolism underlies complexity and capacity.}, journal = {The Journal of physiology}, volume = {586}, number = {1}, pages = {83-95}, pmid = {17947307}, issn = {0022-3751}, support = {R24 RR017718/RR/NCRR NIH HHS/United States ; RR 17718/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Energy Metabolism/physiology ; Humans ; Models, Animal ; Motor Activity/*physiology ; Oxygen/*metabolism ; Oxygen Consumption/physiology ; Thermodynamics ; }, abstract = {The evolution of biological complexity beyond single-celled organisms was linked temporally with the development of an oxygen atmosphere. Functionally, this linkage can be attributed to oxygen ranking high in both abundance and electronegativity amongst the stable elements of the universe. That is, reduction of oxygen provides for close to the largest possible transfer of energy for each electron transfer reaction. This suggests the general hypothesis that the steep thermodynamic gradient of an oxygen environment was permissive for the development of multicellular complexity. A corollary of this hypothesis is that aerobic metabolism underwrites complex biological function mechanistically at all levels of organization. The strong contemporary functional association of aerobic metabolism with both physical capacity and health is presumably a product of the integral role of oxygen in our evolutionary history. Here we provide arguments from thermodynamics, evolution, metabolic network analysis, clinical observations and animal models that are in accord with the centrality of oxygen in biology.}, } @article {pmid17943195, year = {2007}, author = {Chapman, EJ and Carrington, JC}, title = {Specialization and evolution of endogenous small RNA pathways.}, journal = {Nature reviews. Genetics}, volume = {8}, number = {11}, pages = {884-896}, doi = {10.1038/nrg2179}, pmid = {17943195}, issn = {1471-0064}, mesh = {Animals ; *Evolution, Molecular ; Humans ; MicroRNAs/*physiology ; Plants/genetics ; RNA Interference/physiology ; RNA, Small Interfering/*physiology ; Signal Transduction/*genetics ; }, abstract = {The specificity of RNA silencing is conferred by small RNA guides that are processed from structured RNA or dsRNA. The core components for small RNA biogenesis and effector functions have proliferated and specialized in eukaryotic lineages, resulting in diversified pathways that control expression of endogenous and exogenous genes, invasive elements and viruses, and repeated sequences. Deployment of small RNA pathways for spatiotemporal regulation of the transcriptome has shaped the evolution of eukaryotic genomes and contributed to the complexity of multicellular organisms.}, } @article {pmid17942298, year = {2007}, author = {Takagi, J}, title = {Structural basis for ligand recognition by integrins.}, journal = {Current opinion in cell biology}, volume = {19}, number = {5}, pages = {557-564}, doi = {10.1016/j.ceb.2007.09.002}, pmid = {17942298}, issn = {0955-0674}, mesh = {Humans ; *Integrins/chemistry/metabolism ; Laminin/chemistry/metabolism ; *Ligands ; Metals/chemistry/metabolism ; Models, Molecular ; Oligopeptides/chemistry/metabolism ; *Protein Conformation ; }, abstract = {Integrins, the major cell surface receptors mediating cell-extracellular matrix (ECM) adhesion, are central to the basic physiology underlying all multicellular organisms. As the complexity of animal body architecture increased, integrins were forced to acquire recognition capabilities toward the wide variety of ECM ligands and cell surface counter-receptors that emerged during evolution. Structural determination of the integrin-ligand complexes for both I domain-containing and non-I domain-containing integrins revealed two fundamentally different types of integrin-binding surfaces. In addition, recent advances in the biochemical and pharmacological characterization of the integrin-ligand interactions are beginning to reveal how integrins achieve specific recognition of wide variety of ligands using a small binding cleft at the subunit interface common to all integrins.}, } @article {pmid17935625, year = {2007}, author = {Carmel, L and Rogozin, IB and Wolf, YI and Koonin, EV}, title = {Patterns of intron gain and conservation in eukaryotic genes.}, journal = {BMC evolutionary biology}, volume = {7}, number = {}, pages = {192}, pmid = {17935625}, issn = {1471-2148}, abstract = {BACKGROUND: The presence of introns in protein-coding genes is a universal feature of eukaryotic genome organization, and the genes of multicellular eukaryotes, typically, contain multiple introns, a substantial fraction of which share position in distant taxa, such as plants and animals. Depending on the methods and data sets used, researchers have reached opposite conclusions on the causes of the high fraction of shared introns in orthologous genes from distant eukaryotes. Some studies conclude that shared intron positions reflect, almost entirely, a remarkable evolutionary conservation, whereas others attribute it to parallel gain of introns. To resolve these contradictions, it is crucial to analyze the evolution of introns by using a model that minimally relies on arbitrary assumptions.

RESULTS: We developed a probabilistic model of evolution that allows for variability of intron gain and loss rates over branches of the phylogenetic tree, individual genes, and individual sites. Applying this model to an extended set of conserved eukaryotic genes, we find that parallel gain, on average, accounts for only approximately 8% of the shared intron positions. However, the distribution of parallel gains over the phylogenetic tree of eukaryotes is highly non-uniform. There are, practically, no parallel gains in closely related lineages, whereas for distant lineages, such as animals and plants, parallel gains appear to contribute up to 20% of the shared intron positions. In accord with these findings, we estimated that ancestral introns have a high probability to be retained in extant genomes, and conversely, that a substantial fraction of extant introns have retained their positions since the early stages of eukaryotic evolution. In addition, the density of sites that are available for intron insertion is estimated to be, approximately, one in seven basepairs.

CONCLUSION: We obtained robust estimates of the contribution of parallel gain to the observed sharing of intron positions between eukaryotic species separated by different evolutionary distances. The results indicate that, although the contribution of parallel gains varies across the phylogenetic tree, the high level of intron position sharing is due, primarily, to evolutionary conservation. Accordingly, numerous introns appear to persist in the same position over hundreds of millions of years of evolution. This is compatible with recent observations of a negative correlation between the rate of intron gain and coding sequence evolution rate of a gene, suggesting that at least some of the introns are functionally relevant.}, } @article {pmid17933098, year = {2007}, author = {England, SJ and Adams, RJ}, title = {Building a dynamic fate map.}, journal = {BioTechniques}, volume = {43}, number = {1 Suppl}, pages = {20-24}, doi = {10.2144/000112510}, pmid = {17933098}, issn = {0736-6205}, support = {G0400709/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Cell Lineage ; Cell Separation/*methods/trends ; Embryo, Mammalian/*cytology/*physiology ; Flow Cytometry/*methods/trends ; Humans ; Image Interpretation, Computer-Assisted/methods ; Microscopy/*methods/trends ; Morphogenesis/*physiology ; Phylogeny ; }, abstract = {How the single-celled egg is transformed through the multicellular embryo into the structurally complex adult remains a significant challenge to developmental biologists today. Historically, fate maps have been used to follow the reorganization of tissue domains through pertinent stages of growth to predict the mechanisms by which the development of form takes place. However to understand the details of morphogenesis and the causes of errors in its execution, it is essential that we record and reconstruct the precise journeys of all cells and their progeny throughout the course of development. This article presents an overview of the key technologies used in the construction of such dynamic, high-resolution fate maps and highlights their real potential for quantitatively analyzing the physical basis of development.}, } @article {pmid17930067, year = {2007}, author = {Lee, B and Tannenbaum, E}, title = {Asexual and sexual replication in sporulating organisms.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {76}, number = {2 Pt 1}, pages = {021909}, doi = {10.1103/PhysRevE.76.021909}, pmid = {17930067}, issn = {1539-3755}, mesh = {Animals ; Biophysics/methods ; Diploidy ; Evolution, Molecular ; Female ; Haploidy ; Humans ; Kinetics ; Male ; Models, Biological ; Models, Statistical ; Models, Theoretical ; Mutation ; *Reproduction ; *Reproduction, Asexual ; Yeasts/*physiology ; }, abstract = {Replication via sporulation is the replication strategy for all multicellular life, and may even be observed in unicellular life (such as with budding yeast). We consider diploid populations replicating via one of two possible sporulation mechanisms. (1) Asexual sporulation, whereby adult organisms produce single-celled diploid spores that grow into adults themselves. (2) Sexual sporulation, whereby adult organisms produce single-celled diploid spores that divide into haploid gametes. The haploid gametes enter a haploid "pool," where they may recombine with other haploids to form a diploid spore that then grows into an adult. We consider a haploid fusion rate given by second-order reaction kinetics. We work with a simplified model where the diploid genome consists of only two chromosomes, each of which may be rendered defective with a single point mutation of the wild-type. We find that the asexual strategy is favored when the rate of spore production is high compared to the characteristic growth rate from a spore to a reproducing adult. Conversely, the sexual strategy is favored when the rate of spore production is low compared to the characteristic growth rate from a spore to a reproducing adult. As the characteristic growth time increases, or as the population density increases, the critical ratio of spore production rate to organism growth rate at which the asexual strategy overtakes the sexual one is pushed to higher values. Therefore, the results of this model suggest that, for complex multicellular organisms, sexual replication is favored at high population densities and low growth and sporulation rates.}, } @article {pmid17926300, year = {2007}, author = {Todd, BD}, title = {Parasites lost? An overlooked hypothesis for the evolution of alternative reproductive strategies in amphibians.}, journal = {The American naturalist}, volume = {170}, number = {5}, pages = {793-799}, doi = {10.1086/521958}, pmid = {17926300}, issn = {1537-5323}, mesh = {Amphibians/immunology/*parasitology/physiology ; Animals ; *Biological Evolution ; Host-Parasite Interactions ; Larva/growth & development/parasitology ; Population Dynamics ; Reproduction/physiology ; }, abstract = {Amphibians exhibit the greatest diversity of reproductive strategies of all tetrapod vertebrates. While authors have traditionally attributed the evolution of these strategies to factors such as complex topography, unpredictable larval environments, and predation on larvae and eggs, support for any of these hypotheses has been limited. Importantly, most authors have ignored parasites, including unicellular pathogens and multicellular parasites, as selective agents capable of influencing amphibian evolution. Insights in disease transmission, amphibian immunity, and their interaction with various life histories require that we consider parasites to be selective pressures in our exploration of the evolution of amphibian reproductive strategies. I review recent findings and describe how these principles converge to form a novel conceptual hypothesis for the evolution of alternative reproductive strategies in amphibians. I offer some specific predictions and recommend that parasites be considered with other selective pressures when constructing formal, falsifiable hypotheses during evaluative studies of amphibian reproductive behavior.}, } @article {pmid17916237, year = {2007}, author = {Irimia, M and Rukov, JL and Penny, D and Roy, SW}, title = {Functional and evolutionary analysis of alternatively spliced genes is consistent with an early eukaryotic origin of alternative splicing.}, journal = {BMC evolutionary biology}, volume = {7}, number = {}, pages = {188}, pmid = {17916237}, issn = {1471-2148}, mesh = {*Alternative Splicing ; Animals ; Databases, Genetic ; *Eukaryotic Cells ; *Evolution, Molecular ; Fungi/genetics ; *Genes ; Humans ; Introns ; Phylogeny ; Plants/genetics ; Spliceosomes ; }, abstract = {BACKGROUND: Alternative splicing has been reported in various eukaryotic groups including plants, apicomplexans, diatoms, amoebae, animals and fungi. However, whether widespread alternative splicing has evolved independently in the different eukaryotic groups or was inherited from their last common ancestor, and may therefore predate multicellularity, is still unknown. To better understand the origin and evolution of alternative splicing and its usage in diverse organisms, we studied alternative splicing in 12 eukaryotic species, comparing rates of alternative splicing across genes of different functional classes, cellular locations, intron/exon structures and evolutionary origins.

RESULTS: For each species, we find that genes from most functional categories are alternatively spliced. Ancient genes (shared between animals, fungi and plants) show high levels of alternative splicing. Genes with products expressed in the nucleus or plasma membrane are generally more alternatively spliced while those expressed in extracellular location show less alternative splicing. We find a clear correspondence between incidence of alternative splicing and intron number per gene both within and between genomes. In general, we find several similarities in patterns of alternative splicing across these diverse eukaryotes.

CONCLUSION: Along with previous studies indicating intron-rich genes with weak intron boundary consensus and complex spliceosomes in ancestral organisms, our results suggest that at least a simple form of alternative splicing may already have been present in the unicellular ancestor of plants, fungi and animals. A role for alternative splicing in the evolution of multicellularity then would largely have arisen by co-opting the preexisting process.}, } @article {pmid17911301, year = {2007}, author = {Yamada, T and Imachi, H and Ohashi, A and Harada, H and Hanada, S and Kamagata, Y and Sekiguchi, Y}, title = {Bellilinea caldifistulae gen. nov., sp. nov. and Longilinea arvoryzae gen. nov., sp. nov., strictly anaerobic, filamentous bacteria of the phylum Chloroflexi isolated from methanogenic propionate-degrading consortia.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {57}, number = {Pt 10}, pages = {2299-2306}, doi = {10.1099/ijs.0.65098-0}, pmid = {17911301}, issn = {1466-5026}, mesh = {Anaerobiosis/physiology ; Bacterial Typing Techniques ; Base Composition ; Carbohydrate Metabolism/physiology ; Chloroflexi/*classification/cytology/*isolation & purification/physiology ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Fatty Acids/analysis ; Genes, rRNA ; Hydrogen-Ion Concentration ; Locomotion/physiology ; Molecular Sequence Data ; Phylogeny ; Proteins/metabolism ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; Sewage/*microbiology ; *Soil Microbiology ; Temperature ; }, abstract = {Thermophilic (strain GOMI-1(T)) and mesophilic (strain KOME-1(T)) strains were isolated from two different cultures of propionate-degrading consortia obtained from thermophilic digester sludge and rice paddy soil, respectively. The two strains were non-spore-forming, non-motile and Gram-negative. Both strains were obligately anaerobic micro-organisms, showing multicellular filamentous morphotypes more than 100 mum in length. The cell width for strain GOMI-1(T) was 0.2-0.4 mum and that of strain KOME-1(T) was 0.4-0.6 mum. Strain GOMI-1(T) could grow at 45-65 degrees C with a pH range of 6.0-7.5 (optimum growth at 55 degrees C, pH 7.0). The temperature range for growth of strain KOME-1(T) was 30-40 degrees C and the pH range was pH 5.0-8.5 (optimum growth around 37 degrees C, pH 7.0). Yeast extract was required for growth of both strains. Strain GOMI-1(T) was able to grow with a number of carbohydrates in the presence of yeast extract. In yeast extract-containing medium, strain KOME-1(T) could utilize proteins and a limited range of sugars for growth. The G+C contents of the DNA of strains GOMI-1(T) and KOME-1(T) were respectively 54.7 and 57.6 mol%. Major fatty acids of strain GOMI-1(T) were C(16 : 0), C(14 : 0) and iso-C(15 : 0), whereas those of strain KOME-1(T) were iso-C(15 : 0), anteiso-C(15 : 0) and C(14 : 0). Based on comparative analysis of 16S rRNA gene sequences of strains GOMI-1(T) and KOME-1(T), the strains were placed in different phylogenetic positions in the class Anaerolineae of the bacterial phylum Chloroflexi. Their phenotypic and genetic traits strongly supported the conclusion that the strains should be described as two independent taxa in the class Anaerolineae. Hence, we propose the names Bellilinea caldifistulae gen. nov., sp. nov., and Longilinea arvoryzae gen. nov., sp. nov., for strains GOMI-1(T) and KOME-1(T). The type strains of Bellilinea caldifistulae and Longilinea arvoryzae are respectively GOMI-1(T) (=JCM 13669(T) =DSM 17877(T)) and KOME-1(T) (=JCM 13670(T) =KTCC 5380(T)).}, } @article {pmid17904596, year = {2007}, author = {Lapcík, O}, title = {Isoflavonoids in non-leguminous taxa: a rarity or a rule?.}, journal = {Phytochemistry}, volume = {68}, number = {22-24}, pages = {2909-2916}, doi = {10.1016/j.phytochem.2007.08.006}, pmid = {17904596}, issn = {0031-9422}, mesh = {Enzymes/metabolism ; Fabaceae/chemistry ; Humans ; Isoflavones/biosynthesis/*chemistry/*classification ; Plant Proteins/metabolism ; }, abstract = {Isoflavonoids are characteristic metabolites in legumes and an overwhelming number of reports concerning them come from the Leguminosae. Nevertheless, the spectrum of isoflavonoid producing taxa includes the representatives of four classes of multicellular plants, namely the Bryopsida, the Pinopsida, the Magnoliopsida and the Liliopsida. At least 59 non-leguminous families have been reported to produce isoflavones sensu lato; coumestans have been reported in 3 families, coumaronochromones in 3, pterocarpans in 9 and rotenoids in 8 families. Prenylated isoflavones have been found in 15 non-leguminous families and isoflavone dimers, heterodimers or oligomers in three families. More than two hundred different isoflavonoid aglycones have been reported in non-legumes altogether. The number of individual structures is even greater if the variety of glycosides are considered. Enzymology and genetics of isoflavonoid biosynthesis have been studied almost exclusively in legumes, with the exception of a few model plants (i.e. Beta vulgaris, Arabidopsis thaliana, Nicotiana tabacum and Zea mays). The key step at the very beginning of the isoflavonoid metabolic pathway is the oxidation of flavanone connected with the migration of aryl moiety from C2 to C3 mediated by a CYP450 enzyme isoflavone synthase (IFS), which has been identified and cloned in multiple legumes and in sugar beet (Beta vulgaris, Chenopodiaceae). No information is available about the enzyme(s) responsible for the biosynthesis of isoflavonoid core in other taxa. Experimental data demonstrates the capability of numerous enzymes of non-legume origin to metabolize isoflavones as alternative substrates to other phenolics.}, } @article {pmid17901115, year = {2008}, author = {Burmeister, C and Lüersen, K and Heinick, A and Hussein, A and Domagalski, M and Walter, RD and Liebau, E}, title = {Oxidative stress in Caenorhabditis elegans: protective effects of the Omega class glutathione transferase (GSTO-1).}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {22}, number = {2}, pages = {343-354}, doi = {10.1096/fj.06-7426com}, pmid = {17901115}, issn = {1530-6860}, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans/enzymology/genetics/*metabolism/ultrastructure ; Caenorhabditis elegans Proteins/chemistry/*classification/genetics/*metabolism ; GATA Transcription Factors/genetics/metabolism ; Gene Deletion ; Gene Expression Regulation ; Genes, Reporter/genetics ; Glutathione Transferase/chemistry/*classification/genetics/*metabolism ; Humans ; Microscopy, Electron, Transmission ; Microscopy, Immunoelectron ; Molecular Sequence Data ; *Oxidative Stress ; Phylogeny ; Promoter Regions, Genetic/genetics ; RNA Interference ; Recombinant Proteins/genetics/metabolism ; Sensitivity and Specificity ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {To elucidate the function of Omega class glutathione transferases (GSTs) (EC 2.5.1.18) in multicellular organisms, the GSTO-1 from Caenorhabditis elegans (GSTO-1; C29E4.7) was investigated. Disc diffusion assays using Escherichia coli overexpressing GSTO-1 provided a test of resistance to long-term exposure under oxidative stress. After affinity purification, the recombinant GSTO-1 had minimal catalytic activity toward classic GST substrates but displayed significant thiol oxidoreductase and dehydroascorbate reductase activity. Microinjection of the GSTO-1-promoter green fluorescent protein construct and immunolocalization by electron microscopy localized the protein exclusively in the intestine of all postembryonic stages of C. elegans. Deletion analysis identified an approximately 300-nucleotide sequence upstream of the ATG start site necessary for GSTO-1 expression. Site-specific mutagenesis of a GATA transcription factor binding motif in the minimal promoter led to the loss of reporter expression. Similarly, RNA interference (RNAi) of Elt-2 indicated the involvement of this gut-specific transcription factor in GSTO-1 expression. Transcriptional up-regulation under stress conditions of GSTO-1 was confirmed by analyzing promoter-reporter constructs in transgenic C. elegans strains. To investigate the function of GSTO-1 in vivo, transgenic animals overexpressing GSTO-1 were generated exhibiting an increased resistance to juglone-, paraquat-, and cumene hydroperoxide-induced oxidative stress. Specific silencing of the GSTO-1 by RNAi created worms with an increased sensitivity to several prooxidants, arsenite, and heat shock. We conclude that the stress-responsive GSTO-1 plays a key role in counteracting environmental stress.}, } @article {pmid17900370, year = {2007}, author = {Kawahara, T and Lambeth, JD}, title = {Molecular evolution of Phox-related regulatory subunits for NADPH oxidase enzymes.}, journal = {BMC evolutionary biology}, volume = {7}, number = {}, pages = {178}, pmid = {17900370}, issn = {1471-2148}, support = {R01 CA105116/CA/NCI NIH HHS/United States ; R01 GM067717/GM/NIGMS NIH HHS/United States ; GM067717/GM/NIGMS NIH HHS/United States ; CA105116/CA/NCI NIH HHS/United States ; R56 CA105116/CA/NCI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing ; Adaptor Proteins, Vesicular Transport/*genetics ; Amino Acid Sequence ; Animals ; Conserved Sequence ; Humans ; NADPH Oxidases/*genetics ; Phylogeny ; Reactive Oxygen Species ; Synteny ; }, abstract = {BACKGROUND: The reactive oxygen-generating NADPH oxidases (Noxes) function in a variety of biological roles, and can be broadly classified into those that are regulated by subunit interactions and those that are regulated by calcium. The prototypical subunit-regulated Nox, Nox2, is the membrane-associated catalytic subunit of the phagocyte NADPH-oxidase. Nox2 forms a heterodimer with the integral membrane protein, p22phox, and this heterodimer binds to the regulatory subunits p47phox, p67phox, p40phox and the small GTPase Rac, triggering superoxide generation. Nox-organizer protein 1 (NOXO1) and Nox-activator 1 (NOXA1), respective homologs of p47phox and p67phox, together with p22phox and Rac, activate Nox1, a non-phagocytic homolog of Nox2. NOXO1 and p22phox also regulate Nox3, whereas Nox4 requires only p22phox. In this study, we have assembled and analyzed amino acid sequences of Nox regulatory subunit orthologs from vertebrates, a urochordate, an echinoderm, a mollusc, a cnidarian, a choanoflagellate, fungi and a slime mold amoeba to investigate the evolutionary history of these subunits.

RESULTS: Ancestral p47phox, p67phox, and p22phox genes are broadly seen in the metazoa, except for the ecdysozoans. The choanoflagellate Monosiga brevicollis, the unicellular organism that is the closest relatives of multicellular animals, encodes early prototypes of p22phox, p47phox as well as the earliest known Nox2-like ancestor of the Nox1-3 subfamily. p67phox- and p47phox-like genes are seen in the sea urchin Strongylocentrotus purpuratus and the limpet Lottia gigantea that also possess Nox2-like co-orthologs of vertebrate Nox1-3. Duplication of primordial p47phox and p67phox genes occurred in vertebrates, with the duplicated branches evolving into NOXO1 and NOXA1. Analysis of characteristic domains of regulatory subunits suggests a novel view of the evolution of Nox: in fish, p40phox participated in regulating both Nox1 and Nox2, but after the appearance of mammals, Nox1 (but not Nox2) became independent of p40phox. In the fish Oryzias latipes, a NOXO1 ortholog retains an autoinhibitory region that is characteristic of mammalian p47phox, and this was subsequently lost from NOXO1 in later vertebrates. Detailed amino acid sequence comparisons identified both putative key residues conserved in characteristic domains and previously unidentified conserved regions. Also, candidate organizer/activator proteins in fungi and amoeba are identified and hypothetical activation models are suggested.

CONCLUSION: This is the first report to provide the comprehensive view of the molecular evolution of regulatory subunits for Nox enzymes. This approach provides clues for understanding the evolution of biochemical and physiological functions for regulatory-subunit-dependent Nox enzymes.}, } @article {pmid17876790, year = {2007}, author = {Heino, J}, title = {The collagen family members as cell adhesion proteins.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {29}, number = {10}, pages = {1001-1010}, doi = {10.1002/bies.20636}, pmid = {17876790}, issn = {0265-9247}, mesh = {Amino Acid Motifs ; Animals ; Binding Sites ; Cell Adhesion/physiology ; Collagen/chemistry/*classification/genetics/*metabolism ; Extracellular Matrix/metabolism ; Glycoproteins/metabolism ; Humans ; Models, Molecular ; Protein Binding ; Protein Denaturation ; Protein Structure, Secondary ; Receptors, Collagen/*chemistry/*metabolism ; }, abstract = {The collagen family of extracellular matrix proteins has played a fundamental role in the evolution of multicellular animals. At the present, 28 triple helical proteins have been named as collagens and they can be divided into several subgroups based on their structural and functional properties. In tissues, the cells are anchored to collagenous structures. Often the interaction is indirect and mediated by matrix glycoproteins, but cells also express receptors, which have the ability to directly bind to the triple helical domains in collagens. Some receptors bind to sites that are abundant in all collagens. However, increasing evidence indicates that the coevolution of collagens and cell adhesion mechanisms has given rise to receptors that bind to specific motifs in collagens. These receptors may also recognize the different members of the large collagen family in a selective manner. This review summarizes the present knowledge about the properties of collagen subtypes as cell adhesion proteins.}, } @article {pmid17849148, year = {2008}, author = {Hovav, R and Udall, JA and Hovav, E and Rapp, R and Flagel, L and Wendel, JF}, title = {A majority of cotton genes are expressed in single-celled fiber.}, journal = {Planta}, volume = {227}, number = {2}, pages = {319-329}, pmid = {17849148}, issn = {0032-0935}, mesh = {Cell Differentiation ; *Cotton Fiber ; Flowers ; *Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Genes, Plant/*genetics ; Gossypium/*genetics/*metabolism ; Oligonucleotide Array Sequence Analysis ; Plant Proteins/genetics ; }, abstract = {Multicellular eukaryotes contain a diversity of cell types, presumably differing from one another in the suite of genes expressed during development. At present, little is known about the proportion of the genome transcribed in most cell types, nor the degree to which global patterns of expression change during cellular differentiation. To address these questions in a model plant system, we studied the unique and highly exaggerated single-celled, epidermal seed trichomes ("cotton") of cultivated cotton (Gossypium hirsutum). By taking advantage of advances in expression profiling and microarray technology, we evaluated the transcriptome of cotton fibers across a developmental time-course, from a few days post-anthesis through primary and secondary wall synthesis stages. Comparisons of gene expression in populations of developing cotton fiber cells to genetically complex reference samples derived from 6 different cotton organs demonstrated that a remarkably high proportion of the cotton genome is transcribed, with 75-94% of the total genome transcribed at each stage. Compared to the reference samples, more than half of all genes were up-regulated during at least one stage of fiber development. These genes were clustered into seven groups of expression profiles that provided new insight into biological processes governing fiber development. Genes implicated in vesicle coating and trafficking were found to be overexpressed throughout all stages of fiber development studied, indicating their important role in maintaining rapid growth of this unique plant cell.}, } @article {pmid17825942, year = {2007}, author = {Whitcomb, SJ and Basu, A and Allis, CD and Bernstein, E}, title = {Polycomb Group proteins: an evolutionary perspective.}, journal = {Trends in genetics : TIG}, volume = {23}, number = {10}, pages = {494-502}, doi = {10.1016/j.tig.2007.08.006}, pmid = {17825942}, issn = {0168-9525}, support = {GM 53512/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Body Patterning ; Drosophila melanogaster ; *Evolution, Molecular ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Polycomb-Group Proteins ; Repressor Proteins/*genetics ; }, abstract = {The chromatin-associated Polycomb Group (PcG) proteins were first identified in genetic screens for homeotic transformations in Drosophila melanogaster. In addition to body patterning in metazoans, members of the PcG are now known to regulate epigenetic cellular memory, pluripotency and stem cell self-renewal. Here, we discuss the functional versatility of the PcG family and the evolutionary history of a subset of these proteins including Drosophila E(z), Pc, Psc, dRing and their homologs in plants and animals. We propose that PcG gene expansion and diversification contributed significantly to the complexity of heritable gene repression mechanisms in extant multicellular organisms.}, } @article {pmid17766865, year = {2007}, author = {Reddy, GSN and Potrafka, RM and Garcia-Pichel, F}, title = {Modestobacter versicolor sp. nov., an actinobacterium from biological soil crusts that produces melanins under oligotrophy, with emended descriptions of the genus Modestobacter and Modestobacter multiseptatus Mevs et al. 2000.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {57}, number = {Pt 9}, pages = {2014-2020}, doi = {10.1099/ijs.0.64932-0}, pmid = {17766865}, issn = {1466-5026}, mesh = {Actinomycetales/chemistry/*classification/*isolation & purification/physiology ; Bacterial Typing Techniques ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Diaminopimelic Acid/analysis ; Fatty Acids/analysis ; Genes, rRNA ; Hydrogen-Ion Concentration ; Locomotion/physiology ; Melanins/*biosynthesis ; Molecular Sequence Data ; Peptidoglycan/chemistry ; Phylogeny ; Quinones/analysis ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; *Soil Microbiology ; Southwestern United States ; Temperature ; }, abstract = {A novel isolate, CP153-2(T), was obtained from topsoil biological crusts in the Colorado Plateau (USA). Colonies were black in colour due to melanin-like pigments when grown on oligotrophic medium, but not when grown on copiotrophic medium. Induction of melanogenesis was independent of growth phase or illumination conditions, including exposure to UVB and UVA radiation, but exposure to UVB could enhance total pigment production and growth under low nitrogen prevented its synthesis. This mode of regulation was previously unknown among melanin-producing bacteria. Polyphasic characterization of the strain revealed that cells were short, straight to curved or irregular rods that developed into pairs and formed multiseptate short filaments, with rare bud-like cells. Short rods were typically motile by means of flagella; multicellular structures tended to be sessile. Cells stained Gram-positive, grew at 4-30 degrees C and had a narrow range of pH tolerance (pH 5-9). The major fatty acids were iso-C(15:0) iso-C(16 : 0), anteiso-C(15 : 0) and C(18 : 1); MK-9(H(4)) was the major respiratory quinone. Its peptidoglycan contained meso-diaminopimelic acid. Based on 16S rRNA gene sequence similarity data, its closest relative (98.1 % similarity) was Modestobacter multiseptatus DSM 44406(T), which is similar morphologically. Based on the above characteristics, strain CP153-2(T) was also assigned to the genus Modestobacter. However, CP153-2(T) had a relatedness of only 49.9 % in whole-genome reassociation comparisons with the type strain of M. multiseptatus and thus formally represents a novel species, for which the name Modestobacter versicolor sp. nov. is proposed. Additional evidence in support of a novel species comes from phenotypic and chemotaxonomic characteristics. Strain CP153-2(T) (=ATCC BAA-1040(T) =DSM 16678(T)) is the type strain of M. versicolor.}, } @article {pmid17720690, year = {2007}, author = {Shavit, L and Penny, D and Hendy, MD and Holland, BR}, title = {The problem of rooting rapid radiations.}, journal = {Molecular biology and evolution}, volume = {24}, number = {11}, pages = {2400-2411}, doi = {10.1093/molbev/msm178}, pmid = {17720690}, issn = {0737-4038}, mesh = {Computer Simulation ; Evolution, Molecular ; Likelihood Functions ; *Models, Genetic ; *Phylogeny ; }, abstract = {There are many examples of groups (such as birds, bees, mammals, multicellular animals, and flowering plants) that have undergone a rapid radiation. In such cases, where there is a combination of short internal and long external branches, correctly estimating and rooting phylogenetic trees is known to be a difficult problem. In this simulation study, we tested the performances of different phylogenetic methods at estimating a tree that models a rapid radiation. We found that maximum likelihood, corrected and uncorrected neighbor-joining, and corrected and uncorrected parsimony, all suffer from biases toward specific tree topologies. In addition, we found that using a single-taxon outgroup to root a tree frequently disrupts an otherwise correct ingroup phylogeny. Moreover, for uncorrected parsimony, we found cases where several individual trees (in which the outgroup was placed incorrectly) were selected more frequently than the correct tree. Even for parameter settings where the correct tree was selected most frequently when using extremely long sequences, for sequences of up to 60,000 nucleotides the incorrectly rooted trees were each selected more frequently than the correct tree. For all the cases tested here, tree estimation using a two taxon outgroup was more accurate than when using a single-taxon outgroup. However, the ingroup was most accurately recovered when no outgroup was used.}, } @article {pmid17715154, year = {2007}, author = {Dacks, JB and Field, MC}, title = {Evolution of the eukaryotic membrane-trafficking system: origin, tempo and mode.}, journal = {Journal of cell science}, volume = {120}, number = {Pt 17}, pages = {2977-2985}, doi = {10.1242/jcs.013250}, pmid = {17715154}, issn = {0021-9533}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Biological Transport/physiology ; Eukaryotic Cells/cytology/*metabolism ; Genomics ; Humans ; Intracellular Membranes/*metabolism ; Phylogeny ; }, abstract = {The emergence of an endomembrane system was a crucial stage in the prokaryote-to-eukaryote evolutionary transition. Recent genomic and molecular evolutionary analyses have provided insight into how this critical system arrived at its modern configuration. The apparent relative absence of prokaryotic antecedents for the endomembrane machinery contrasts with the situation for mitochondria, plastids and the nucleus. Overall, the evidence suggests an autogenous origin for the eukaryotic membrane-trafficking machinery. The emerging picture is that early eukaryotic ancestors had a complex endomembrane system, which implies that this cellular system evolved relatively rapidly after the proto-eukaryote diverged away from the other prokaryotic lines. Many of the components of the trafficking system are the result of gene duplications that have produced proteins that have similar functions but differ in their subcellular location. A proto-eukaryote possessing a very simple trafficking system could thus have evolved to near modern complexity in the last common eukaryotic ancestor (LCEA) via paralogous gene family expansion of the proteins encoding organelle identity. The descendents of this common ancestor have undergone further modification of the trafficking machinery; unicellular simplicity and multicellular complexity are the prevailing trend, but there are some remarkable counter-examples.}, } @article {pmid17714660, year = {2007}, author = {West, SA and Griffin, AS and Gardner, A}, title = {Evolutionary explanations for cooperation.}, journal = {Current biology : CB}, volume = {17}, number = {16}, pages = {R661-72}, doi = {10.1016/j.cub.2007.06.004}, pmid = {17714660}, issn = {0960-9822}, mesh = {Animals ; *Biological Evolution ; Cell Communication ; *Cooperative Behavior ; Eukaryotic Cells/metabolism ; *Genes ; Humans ; }, abstract = {Natural selection favours genes that increase an organism's ability to survive and reproduce. This would appear to lead to a world dominated by selfish behaviour. However, cooperation can be found at all levels of biological organisation: genes cooperate in genomes, organelles cooperate to form eukaryotic cells, cells cooperate to make multicellular organisms, bacterial parasites cooperate to overcome host defences, animals breed cooperatively, and humans and insects cooperate to build societies. Over the last 40 years, biologists have developed a theoretical framework that can explain cooperation at all these levels. Here, we summarise this theory, illustrate how it may be applied to real organisms and discuss future directions.}, } @article {pmid17698402, year = {2007}, author = {Stiller, JW}, title = {Plastid endosymbiosis, genome evolution and the origin of green plants.}, journal = {Trends in plant science}, volume = {12}, number = {9}, pages = {391-396}, doi = {10.1016/j.tplants.2007.08.002}, pmid = {17698402}, issn = {1360-1385}, mesh = {*Evolution, Molecular ; *Genome, Plant ; Plants/*genetics ; Plastids/*genetics ; Symbiosis/*genetics ; }, abstract = {Evolutionary relationships among complex, multicellular eukaryotes are generally interpreted within the framework of molecular sequence-based phylogenies that suggest green plants and animals are only distantly related on the eukaryotic tree. However, important anomalies have been reported in phylogenomic analyses, including several that relate specifically to green plant evolution. In addition, plants and animals share molecular, biochemical and genome-level features that suggest a relatively close relationship between the two groups. This article explores the impacts of plastid endosymbioses on nuclear genomes, how they can explain incongruent phylogenetic signals in molecular data sets and reconcile conflicts among different sources of comparative data. Specifically, I argue that the large influx of plastid DNA into plant and algal nuclear genomes has resulted in tree-building artifacts that obscure a relatively close evolutionary relationship between green plants and animals.}, } @article {pmid17698300, year = {2007}, author = {Sasaki, G and Katoh, K and Hirose, N and Suga, H and Kuma, K and Miyata, T and Su, ZH}, title = {Multiple receptor-like kinase cDNAs from liverwort Marchantia polymorpha and two charophycean green algae, Closterium ehrenbergii and Nitella axillaris: Extensive gene duplications and gene shufflings in the early evolution of streptophytes.}, journal = {Gene}, volume = {401}, number = {1-2}, pages = {135-144}, doi = {10.1016/j.gene.2007.07.009}, pmid = {17698300}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Chlorophyta/classification/enzymology/*genetics ; Cloning, Molecular ; *DNA Shuffling ; DNA, Complementary/*genetics ; *Evolution, Molecular ; *Gene Duplication ; *Genes, Plant ; Marchantia/classification/enzymology/*genetics ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Protein Serine-Threonine Kinases/*genetics ; Protein Structure, Tertiary ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; }, abstract = {Plant receptor-like kinases (RLKs) comprise a large family with more than several hundred members in vascular plants. The RLK family is thought to have diverged specifically in the plant kingdom, and no family member has been identified in other lineages except for animals and Plasmodium, both of which have RLK related families of small size. To know the time of divergence of RLK family members by gene duplications and domain shufflings, comprehensive isolations of RLK cDNAs were performed from a nonvascular plant, liverwort Marchantia polymorpha and two charophycean green algae, Closterium ehrenbergii, and Nitella axillaris, thought to be the closest relatives to land plants. We obtained twenty-nine, fourteen, and thirteen RLK related cDNAs from M. polymorpha, C. ehrenbergii, and N. axillaris, respectively. The amino acid sequences of these RLKs were compared with those of vascular plants, and phylogenetic trees were inferred by GAMT, a genetic algorithm-based maximum likelihood (ML) method that outputs multiple trees, together with best one. The inferred ML trees revealed ancient gene duplications generating subfamilies with different domain organizations, which occurred extensively at least before the divergence of vascular and nonvascular plants. Rather it remains possible that the extensive gene duplications occurred during the early evolution of streptophytes. Multicellular-specific somatic embryogenesis receptor kinase (SERK) involved in somatic embryogenesis was found in a unicellular alga C. ehrenbergii, suggesting the evolution of SERK by gene recruitment of a unicellular gene.}, } @article {pmid17691453, year = {2007}, author = {Tatarinov, LP}, title = {[Molecular genetics and epigenetics in the morphogenesis mechanisms].}, journal = {Zhurnal obshchei biologii}, volume = {68}, number = {3}, pages = {165-169}, pmid = {17691453}, issn = {0044-4596}, mesh = {Animals ; *Epigenesis, Genetic ; *Evolution, Molecular ; *Genes, Homeobox ; Molecular Biology ; }, abstract = {The progress of molecular genetics principally changed the views on heredity and, in the long run, wrecked the synthetic theory of evolution, designed for the microevolutionary processes in populations only. Molecular genetics as a whole is sufficient for analyzing evolutionary processes in viruses and prokaryotes. But in multicellular organisms, with the advent of more complicated morphogenesis, epigenetic processes took effect. Appealing exclusively to the integrity of the organism in ontogeny is insufficient for the understanding of these processes; further studies of the molecular basis for this integrity are required. The discovery of homeobox genes was an important step on this path. The theory of evolution should include not only the molecular processes but also the laws of ecosystem and biosphere processes, which study requires handling many problems of ecology, parasitology, palaeontology, and geology. All these fields together comprise an enormous area of knowledge for which the development of a unified theory is scarcely possible.}, } @article {pmid17688684, year = {2007}, author = {Kuramae, EE and Robert, V and Echavarri-Erasun, C and Boekhout, T}, title = {Cophenetic correlation analysis as a strategy to select phylogenetically informative proteins: an example from the fungal kingdom.}, journal = {BMC evolutionary biology}, volume = {7}, number = {}, pages = {134}, pmid = {17688684}, issn = {1471-2148}, mesh = {Databases, Protein ; Evolution, Molecular ; Fungal Proteins/*genetics ; Fungi/classification/*genetics ; Genome, Fungal ; *Phylogeny ; }, abstract = {BACKGROUND: The construction of robust and well resolved phylogenetic trees is important for our understanding of many, if not all biological processes, including speciation and origin of higher taxa, genome evolution, metabolic diversification, multicellularity, origin of life styles, pathogenicity and so on. Many older phylogenies were not well supported due to insufficient phylogenetic signal present in the single or few genes used in phylogenetic reconstructions. Importantly, single gene phylogenies were not always found to be congruent. The phylogenetic signal may, therefore, be increased by enlarging the number of genes included in phylogenetic studies. Unfortunately, concatenation of many genes does not take into consideration the evolutionary history of each individual gene. Here, we describe an approach to select informative phylogenetic proteins to be used in the Tree of Life (TOL) and barcoding projects by comparing the cophenetic correlation coefficients (CCC) among individual protein distance matrices of proteins, using the fungi as an example. The method demonstrated that the quality and number of concatenated proteins is important for a reliable estimation of TOL. Approximately 40-45 concatenated proteins seem needed to resolve fungal TOL.

RESULTS: In total 4852 orthologous proteins (KOGs) were assigned among 33 fungal genomes from the Asco- and Basidiomycota and 70 of these represented single copy proteins. The individual protein distance matrices based on 531 concatenated proteins that has been used for phylogeny reconstruction before 14 were compared one with another in order to select those with the highest CCC, which then was used as a reference. This reference distance matrix was compared with those of the 70 single copy proteins selected and their CCC values were calculated. Sixty four KOGs showed a CCC above 0.50 and these were further considered for their phylogenetic potential. Proteins belonging to the cellular processes and signaling KOG category seem more informative than those belonging to the other three categories: information storage and processing; metabolism; and the poorly characterized category. After concatenation of 40 proteins the topology of the phylogenetic tree remained stable, but after concatenation of 60 or more proteins the bootstrap support values of some branches decreased, most likely due to the inclusion of proteins with lowers CCC values. The selection of protein sequences to be used in various TOL projects remains a critical and important process. The method described in this paper will contribute to a more objective selection of phylogenetically informative protein sequences.

CONCLUSION: This study provides candidate protein sequences to be considered as phylogenetic markers in different branches of fungal TOL. The selection procedure described here will be useful to select informative protein sequences to resolve branches of TOL that contain few or no species with completely sequenced genomes. The robust phylogenetic trees resulting from this method may contribute to our understanding of organismal diversification processes. The method proposed can be extended easily to other branches of TOL.}, } @article {pmid17687928, year = {2007}, author = {Maciejewska, A}, title = {Molecular phylogenetics of representative Paramecium species.}, journal = {Folia biologica}, volume = {55}, number = {1-2}, pages = {1-8}, doi = {10.3409/173491607780006335}, pmid = {17687928}, issn = {0015-5497}, mesh = {Animals ; Paramecium/classification/*genetics ; *Phylogeny ; RNA, Protozoan/*genetics ; Random Amplified Polymorphic DNA Technique ; }, abstract = {The genus Paramecium has been known to science for 250 years and contains some of the most widely studied species of ciliates. At present, the basic research object for phylogenetic studies is the genome of various paramecia. One of the most widely used markers are genes coding for various rRNA's. Comparative analyses of sequences coding rRNA were applied for resolving the systematic position of some paramecia species and also for the establishment of an accurate taxonomy of Paramecium. Paramecia were also model organisms for their systematic group in more general studies in a comparative analysis among ciliates, fungi, plants and multicellular animals, illustrating the evolutionary relationships between Archaebacteria and Eucaryota. A new, revolutionary genealogy proposed the shifting of presumptively advanced groups towards more primitive ones, and traditionally primitive forms were located closer to highly specialized taxa, but rRNA analysis did not unambiguously resolve associations within the studied groups. Because of the aforementioned concerns, the number of molecular markers used for alternative studies is growing, such as genes coding proteins from the Hsp family or histone proteins. Other promising candidate markers may be hemoglobin genes or genes coding á-tubulins. In case of comparative analyses ofnucleotide sequences, the outcome of the research usually depends upon a subjective choice of DNA. One of the directions of research in molecular phylogenetics include indirect methods that allow for an estimation of entire genomes, for example RAPD-PCR-fingerprinting.}, } @article {pmid17687670, year = {2007}, author = {Heidenreich, E}, title = {Adaptive mutation in Saccharomyces cerevisiae.}, journal = {Critical reviews in biochemistry and molecular biology}, volume = {42}, number = {4}, pages = {285-311}, doi = {10.1080/10409230701507773}, pmid = {17687670}, issn = {1040-9238}, mesh = {*Adaptation, Biological/genetics ; DNA Repair ; *Mutation ; Saccharomyces cerevisiae/*genetics ; }, abstract = {Adaptive mutation is a generic term for processes that allow individual cells of nonproliferating cell populations to acquire advantageous mutations and thereby to overcome the strong selective pressure of proliferation-limiting environmental conditions. Prerequisites for an occurrence of adaptive mutation are that the selective conditions are nonlethal and that a restart of proliferation may be accomplished by some genetic change in principle. The importance of adaptive mutation is derived from the assumption that it may, on the one hand, result in an accelerated evolution of microorganisms and, on the other, in multicellular organisms may contribute to a breakout of somatic cells from negative growth regulation, i.e., to cancerogenesis. Most information on adaptive mutation in eukaryotes has been gained with the budding yeast Saccharomyces cerevisiae. This review focuses comprehensively on adaptive mutation in this organism and summarizes our current understanding of this issue.}, } @article {pmid17687336, year = {2007}, author = {Gatenby, RA and Smallbone, K and Maini, PK and Rose, F and Averill, J and Nagle, RB and Worrall, L and Gillies, RJ}, title = {Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer.}, journal = {British journal of cancer}, volume = {97}, number = {5}, pages = {646-653}, pmid = {17687336}, issn = {0007-0920}, mesh = {*Adaptation, Physiological ; Breast Neoplasms/metabolism/*pathology ; Carcinoma in Situ/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Cell Hypoxia ; Female ; Glucose Transporter Type 1/metabolism ; Humans ; Hypoxia/physiopathology ; Immunohistochemistry ; Models, Biological ; Neoplasm Invasiveness ; Sodium-Hydrogen Exchangers/metabolism ; }, abstract = {Conceptual models of carcinogenesis typically consist of an evolutionary sequence of heritable changes in genes controlling proliferation, apoptosis, and senescence. We propose that these steps are necessary but not sufficient to produce invasive breast cancer because intraductal tumour growth is also constrained by hypoxia and acidosis that develop as cells proliferate into the lumen and away from the underlying vessels. This requires evolution of glycolytic and acid-resistant phenotypes that, we hypothesise, is critical for emergence of invasive cancer. Mathematical models demonstrate severe hypoxia and acidosis in regions of intraductal tumours more than 100 microm from the basement membrane. Subsequent evolution of glycolytic and acid-resistant phenotypes leads to invasive proliferation. Multicellular spheroids recapitulating ductal carcinoma in situ (DCIS) microenvironmental conditions demonstrate upregulated glucose transporter 1 (GLUT1) as adaptation to hypoxia followed by growth into normoxic regions in qualitative agreement with model predictions. Clinical specimens of DCIS exhibit periluminal distribution of GLUT-1 and Na(+)/H(+) exchanger (NHE) indicating transcriptional activation by hypoxia and clusters of the same phenotype in the peripheral, presumably normoxic regions similar to the pattern predicted by the models and observed in spheroids. Upregulated GLUT-1 and NHE-1 were observed in microinvasive foci and adjacent intraductal cells. Adaptation to hypoxia and acidosis may represent key events in transition from in situ to invasive cancer.}, } @article {pmid17674703, year = {2007}, author = {Shemarova, IV and Nesterov, VP}, title = {[Evolution of mechanisms of Ca2+ -signaling. Significance of Ca2+-messenger systems during transition of organisms to multicellularity].}, journal = {Zhurnal evoliutsionnoi biokhimii i fiziologii}, volume = {43}, number = {2}, pages = {117-124}, pmid = {17674703}, issn = {0044-4529}, mesh = {Animals ; *Biological Evolution ; *Calcium Signaling ; Cell Communication/physiology ; Cell Movement/physiology ; Cyclic ADP-Ribose/physiology ; Hydrozoa/cytology/*physiology ; Porifera/cytology/*physiology ; }, abstract = {The review considers Ca2+ -messenger systems in primitive multicellulars (sponges and hydrozoa organisms). Analysis is performed of Ca2+ participation in regulation of early development of the organisms, their mobility, metamorphosis, chemoreception, and some other functions.}, } @article {pmid17670751, year = {2007}, author = {Steinmacher, DA and Krohn, NG and Dantas, AC and Stefenon, VM and Clement, CR and Guerra, MP}, title = {Somatic embryogenesis in peach palm using the thin cell layer technique: induction, morpho-histological aspects and AFLP analysis of somaclonal variation.}, journal = {Annals of botany}, volume = {100}, number = {4}, pages = {699-709}, pmid = {17670751}, issn = {0305-7364}, mesh = {Amplified Fragment Length Polymorphism Analysis ; Arecaceae/cytology/*embryology/genetics ; Cloning, Organism/*methods ; Embryonic Development/drug effects/*physiology ; Meristem/cytology/embryology/genetics ; Picloram/administration & dosage/pharmacology ; Plant Shoots/cytology/embryology/genetics ; }, abstract = {BACKGROUND AND AIMS: The thin cell layer (TCL) technique is based on the use of very small explants and has allowed enhanced in vitro morphogenesis in several plant species. The present study evaluated the TCL technique as a procedure for somatic embryo production and plantlet regeneration of peach palm.

METHODS: TCL explants from different positions in the shoot apex and leaf sheath of peach palm were cultivated in MS culture medium supplemented with 0-600 microM Picloram in the presence of activated charcoal. The production of primary calli and embryogenic calli was evaluated in these different conditions. Histological and amplified fragment length polymorphism (AFLP) analyses were conducted to study in vitro morphogenetic responses and genetic stability, respectively, of the regenerated plantlets.

KEY RESULTS: Abundant primary callus induction was observed from TCLs of the shoot meristem in culture media supplemented with 150-600 microM Picloram (83-97%, respectively). The production of embryogenic calli depends on Picloram concentration and explant position. The best response observed was 43% embryogenic callus production from shoot meristem TCL on 300 microM Picloram. In maturation conditions, 34+/-4 somatic embryos per embryogenic callus were obtained, and 45.0+/-3.4% of these fully developed somatic embryos were converted, resulting in plantlets ready for acclimatization, of which 80% survived. Histological studies revealed that the first cellular division events occurred in cells adjacent to vascular tissue, resulting in primary calli, whose growth was ensured by a meristematic zone. A multicellular origin of the resulting somatic embryos arising from the meristematic zone is suggested. During maturation, histological analyses revealed bipolarization of the somatic embryos, as well as the development of new somatic embryos. AFLP analyses revealed that 92% of the regenerated plantlets were true to type. The use of TCL explants considerably improves the number of calli and somatic embryos produced in comparison with previously described protocols for in vitro regeneration of peach palm.

CONCLUSIONS: The present study suggests that the TCL somatic embryogenesis protocol developed is feasible, although it still requires further optimization for in vitro multiplication of peach palm, especially the use of similar explants obtained from adult palm trees.}, } @article {pmid17668933, year = {2007}, author = {Esser, AT and Smith, KC and Gowrishankar, TR and Weaver, JC}, title = {Towards solid tumor treatment by irreversible electroporation: intrinsic redistribution of fields and currents in tissue.}, journal = {Technology in cancer research & treatment}, volume = {6}, number = {4}, pages = {261-274}, doi = {10.1177/153303460700600402}, pmid = {17668933}, issn = {1533-0346}, support = {R01-GM63857/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Death ; *Cell Membrane Permeability ; Electricity ; Electroporation/*methods ; Hot Temperature/*therapeutic use ; Humans ; Neoplasms/*surgery ; }, abstract = {Local and drug-free tissue treatment by irreversible electroporation (IRE) involves the creation of aqueous pores in a cell's plasma membrane (PM) and leads to non-thermal cell death by necrosis. To investigate explicit pore-based effects we use two-dimensional system models with different spatial scales. The first is a multicellular system model (spatial scale 100 mum) that has irregularly shaped cells, and quantitatively describes dynamic (creation and destruction, evolution in pore size) pore behavior at the PM. The second is a tissue model (spatial scale 200 mm) that is constructed from a unit cell and uses the asymptotic (fixed pore size) electroporation model. Both system models show that significant redistribution of fields and currents occurs through transient PM pores. Pore histograms for the multicellular model demonstrate the simultaneous presence of small and large pores during IRE pulses. The associated significant increase of PM permeability may prove to be essential to understanding how cell death by necrosis occurs. The averaged tissue conductivity in both models increases during IRE pulses because of electroporation. This leads to greater electrical dissipation (heating) and, thus, to larger temperature increases than suggested by tissue models with passive and static electrical properties.}, } @article {pmid19384428, year = {2007}, author = {Holt, JE and Ly-Huynh, JD and Efthymiadis, A and Hime, GR and Loveland, KL and Jans, DA}, title = {Regulation of Nuclear Import During Differentiation; The IMP alpha Gene Family and Spermatogenesis.}, journal = {Current genomics}, volume = {8}, number = {5}, pages = {323-334}, pmid = {19384428}, issn = {1389-2029}, abstract = {Access to nuclear genes in eukaryotes is provided by members of the importin (IMP) superfamily of proteins, which are of alpha- or beta-types, the best understood nuclear import pathway being mediated by a heterodimer of an IMP alpha and IMP beta1. IMP alpha recognises specific targeting signals on cargo proteins, while IMP beta1 mediates passage into, and release within, the nucleus by interacting with other components of the transport machinery, including the monomeric guanine nucleotide binding protein Ran. In this manner, hundreds of different proteins can be targeted specifically into the nucleus in a tightly regulated fashion. The IMP alpha gene family has expanded during evolution, with only a single IMP alpha (Srp1p) gene in budding yeast, and three (IMP alpha1, 2/pendulin and 3) and five (IMP alpha1, -2, -3, -4 and -6) IMP alpha genes in Drosophila melanogaster and mouse respectively, which fall into three phylogenetically distinct groups. The fact that IMP alpha3 and IMP alpha2 are only present in metazoans implies that they emerged during the evolution of multicellular animals to perform specialised roles in particular cells and tissues. This review describes what is known of the IMP alpha gene family in mouse and in D. melanogaster, including a comparitive examination of their mRNA expression profiles in a highly differentiated tissue, the testis. The clear implication of their highly regulated synthesis during the course of spermatogenesis is that the different IMP alphas have distinct expression patterns during cellular differentiation, implying tissue/cell type-specific roles.}, } @article {pmid17660714, year = {2007}, author = {Sherman, M}, title = {Universal genome in the origin of metazoa: thoughts about evolution.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {6}, number = {15}, pages = {1873-1877}, doi = {10.4161/cc.6.15.4557}, pmid = {17660714}, issn = {1551-4005}, mesh = {Animals ; *Biological Evolution ; Genome/*genetics ; Humans ; }, abstract = {Recent advances in paleontology, genome analysis, genetics and embryology raise a number of questions about the origin of Animal Kingdom. These questions include:(1) seemingly simultaneous appearance of diverse Metazoan phyla in Cambrian period, (2) similarities of genomes among Metazoan phyla of diverse complexity, (3) seemingly excessive complexity of genomes of lower taxons and (4) similar genetic switches of functionally similar but non-homologous developmental programs. Here I propose an experimentally testable hypothesis of Universal Genome that addresses these questions. According to this model, (a) the Universal Genome that encodes all major developmental programs essential for various phyla of Metazoa emerged in a unicellular or a primitive multicellular organism shortly before the Cambrian period; (b) The Metazoan phyla, all having similar genomes, are nonetheless so distinct because they utilize specific combinations of developmental programs. This model has two major predictions, first that a significant fraction of genetic information in lower taxons must be functionally useless but becomes useful in higher taxons, and second that one should be able to turn on in lower taxons some of the complex latent developmental programs, e.g., a program of eye development or antibody synthesis in sea urchin. An example of natural turning on of a complex latent program in a lower taxon is discussed.}, } @article {pmid17653271, year = {2007}, author = {Shaish, L and Abelson, A and Rinkevich, B}, title = {How plastic can phenotypic plasticity be? The branching coral Stylophora pistillata as a model system.}, journal = {PloS one}, volume = {2}, number = {7}, pages = {e644}, pmid = {17653271}, issn = {1932-6203}, mesh = {Animals ; Anthozoa/anatomy & histology/drug effects/*genetics/growth & development ; Anthraquinones/pharmacology ; Ecosystem ; Evolution, Molecular ; Indian Ocean ; Israel ; Marine Biology/methods ; Models, Structural ; *Phenotype ; Photography ; }, abstract = {Phenotypic plasticity enables multicellular organisms to adjust morphologies and various life history traits to variable environmental challenges. Here, we elucidate fixed and plastic architectural rules for colony astogeny in multiple types of colonial ramets, propagated by cutting from genets of the branching coral Stylophora pistillata from Eilat, the Red Sea. We examined 16 morphometric parameters on 136 one-year old S. pistillata colonies (of seven genotypes), originating from small fragments belonging, each, to one of three single-branch types (single tips, start-up, and advanced bifurcating tips) or to structural preparative manipulations (representing a single or two growth axes). Experiments were guided by the rationale that in colonial forms, complexity of evolving phenotypic plasticity can be associated with a degree of structural modularity, where shapes are approached by erecting iterative growth patterns at different levels of coral-colony organization. Analyses revealed plastic morphometric characters at branch level, and predetermined morphometric traits at colony level (only single trait exhibited plasticity under extreme manipulation state). Therefore, under the experimental manipulations of this study, phenotypic plasticity in S. pistillata appears to be related to branch level of organization, whereas colony traits are controlled by predetermined genetic architectural rules. Each level of organization undergoes its own mode of astogeny. However, depending on the original ramet structure, the spherical 3-D colonial architecture in this species is orchestrated and assembled by both developmental trajectories at the branch level, and traits at the colony level of organization. In nature, branching colonial forms are often subjected to harsh environmental conditions that cause fragmentation of colony into ramets of different sizes and structures. Developmental traits that are plastic, responding to fragment structure and are not predetermine in controlling astogeny, allow formation of species-specific architecture product through integrated but variable developmental routes. This adaptive plasticity or regeneration is an efficient mechanism by which isolated fragments of branching coral species cope with external environmental forces.}, } @article {pmid17652078, year = {2007}, author = {Caffaro, CE and Hirschberg, CB and Berninsone, PM}, title = {Functional redundancy between two Caenorhabditis elegans nucleotide sugar transporters with a novel transport mechanism.}, journal = {The Journal of biological chemistry}, volume = {282}, number = {38}, pages = {27970-27975}, doi = {10.1074/jbc.M704485200}, pmid = {17652078}, issn = {0021-9258}, support = {GM-30365/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Transport ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/*metabolism/physiology ; Carbohydrates/chemistry ; Evolution, Molecular ; Genome ; Membrane Transport Proteins/chemistry ; Models, Biological ; Nucleotide Transport Proteins/*chemistry ; Phylogeny ; RNA Interference ; Saccharomyces cerevisiae/metabolism ; Subcellular Fractions ; }, abstract = {Transporters of nucleotide sugars regulate the availability of these substrates required for glycosylation reactions in the lumen of the Golgi apparatus and play an important role in the development of multicellular organisms. Caenorhabditis elegans has seven different sugars in its glycoconjugates, although 18 putative nucleotide sugar transporters are encoded in the genome. Among these, SQV-7, SRF-3, and CO3H5.2 exhibit partially overlapping substrate specificity and expression patterns. We now report evidence of functional redundancy between transporters CO3H5.2 and SRF-3. Reducing the activity of the CO3H5.2 gene product by RNA interference (RNAi) in SRF-3 mutants results in oocyte accumulation and abnormal gonad morphology, whereas comparable RNAi treatment of wild type or RNAi hypersensitive C. elegans strains does not cause detectable defects. We hypothesize this genetic enhancement to be a mechanism to ensure adequate glycoconjugate biosynthesis required for normal tissue development in multicellular organisms. Furthermore, we show that transporters SRF-3 and CO3H5.2, which are closely related in the phylogenetic tree, share a simultaneous and independent substrate transport mechanism that is different from the competitive one previously demonstrated for transporter SQV-7, which shares a lower amino acid sequence identity with CO3H5.2 and SRF-3. Therefore, different mechanisms for transporting multiple nucleotide sugars may have evolved parallel to transporter amino acid divergence.}, } @article {pmid17646893, year = {2007}, author = {Duncan, L and Nishii, I and Harryman, A and Buckley, S and Howard, A and Friedman, NR and Miller, SM}, title = {The VARL gene family and the evolutionary origins of the master cell-type regulatory gene, regA, in Volvox carteri.}, journal = {Journal of molecular evolution}, volume = {65}, number = {1}, pages = {1-11}, pmid = {17646893}, issn = {0022-2844}, support = {GM 08663/GM/NIGMS NIH HHS/United States ; R25-GM55036/GM/NIGMS NIH HHS/United States ; }, mesh = {Algal Proteins/*genetics ; Amino Acid Sequence ; Animals ; Base Sequence ; Chlamydomonas reinhardtii/*genetics ; Databases, Genetic ; *Evolution, Molecular ; Molecular Sequence Data ; *Multigene Family ; Phylogeny ; Protein Structure, Tertiary/genetics ; Sequence Alignment ; Volvox/*genetics ; }, abstract = {Chlamydomonas reinhardtii, Volvox carteri, and their relatives in the family Volvocaceae provide an excellent opportunity for studying how multicellular organisms with differentiated cell types evolved from unicellular ancestors. While C. reinhardtii is unicellular, V. carteri is multicellular with two cell types, one of which resembles C. reinhardtii cytologically but is terminally differentiated. Maintenance of this "somatic cell" fate is controlled by RegA, a putative transcription factor. We recently showed that RegA shares a conserved region with several predicted V. carteri and C. reinhardtii proteins and that this region, the VARL domain, is likely to include a DNA-binding SAND domain. As the next step toward understanding the evolutionary origins of the regA gene, we analyzed the genome sequences of C. reinhardtii and V. carteri to identify additional genes with the potential to encode VARL domain proteins. Here we report that the VARL gene family, which consists of 12 members in C. reinhardtii and 14 in V. carteri, has experienced a complex evolutionary history in which members of the family have been both gained and lost over time, although several pairs of potentially orthologous genes can still be identified. We find that regA is part of a tandem array of four VARL genes in V. carteri but that a similar array is absent in C. reinhardtii. Most importantly, our phylogenetic analysis suggests that a proto-regA gene was present in a common unicellular ancestor of V. carteri and C. reinhardtii and that this gene was lost in the latter lineage.}, } @article {pmid17637734, year = {2007}, author = {Baer, CF and Miyamoto, MM and Denver, DR}, title = {Mutation rate variation in multicellular eukaryotes: causes and consequences.}, journal = {Nature reviews. Genetics}, volume = {8}, number = {8}, pages = {619-631}, doi = {10.1038/nrg2158}, pmid = {17637734}, issn = {1471-0056}, mesh = {Animals ; DNA Repair ; DNA Replication ; Eukaryotic Cells ; Evolution, Molecular ; Female ; Genetic Variation ; Genome ; Humans ; Male ; *Models, Genetic ; Mutagens/toxicity ; *Mutation ; Pedigree ; }, abstract = {A basic knowledge about mutation rates is central to our understanding of a myriad of evolutionary phenomena, including the maintenance of sex and rates of molecular evolution. Although there is substantial evidence that mutation rates vary among taxa, relatively little is known about the factors that underlie this variation at an empirical level, particularly in multicellular eukaryotes. Here we integrate several disparate lines of theoretical and empirical inquiry into a unified framework to guide future studies that are aimed at understanding why and how mutation rates evolve in multicellular species.}, } @article {pmid17631436, year = {2007}, author = {Barile, L and Messina, E and Giacomello, A and Marbán, E}, title = {Endogenous cardiac stem cells.}, journal = {Progress in cardiovascular diseases}, volume = {50}, number = {1}, pages = {31-48}, doi = {10.1016/j.pcad.2007.03.005}, pmid = {17631436}, issn = {0033-0620}, support = {U54 HL081028/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cell Count ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Cell Separation/methods ; Cell Transplantation/*methods ; Heart Diseases/pathology/physiopathology/*surgery ; Humans ; Myocardium/cytology ; Myocytes, Cardiac/*physiology/*transplantation ; Regeneration ; *Stem Cell Transplantation ; Stem Cells/*physiology ; Tissue Culture Techniques ; }, abstract = {In the past few years it has been established that the heart contains a reservoir of stem and progenitor cells. These cells are positive for various stem/progenitor cell markers (Kit, Sca-1, Isl-1, and Side Population (SP) properties). The relationship between the various cardiac stem cells (CSC) and progenitor cells described awaits clarification. Furthermore, they may open a new therapeutic strategies of cardiac repair based on the regeneration potential of cardiac stem cells. Currently, cellular cardiomyoplasty is actively explored as means of regenerating damaged myocardium using several different cell types. CSCs seem a logical cell source to exploit for cardiac regeneration therapy. Their presence into the heart, the frequent co-expression of early cardiac progenitor transcription factors, and the capability for ex vivo and in vivo differentiation toward the cardiac lineages offer promise of enhanced cardiogenicity compared to other cell sources. CSCs, when isolated from various animal models by selection based on c-Kit, Sca-1, and/or MDR1, have shown cardiac regeneration potential in vivo following injection in the infracted myocardium. Recently, we have successfully isolated CSCs from small biopsies of human myocardium and expanded them ex vivo by many folds without losing differentiation potential into cardiomyocytes and vascular cells, bringing autologous transplantation of CSCs closer to clinical evaluation. These cells are spontaneously shed from human surgical specimens and murine heart samples in primary culture. This heterogeneous population of cells forms multi-cellular clusters, dubbed cardiospheres (CSs), in suspension culture. CSs are composed of clonally-derived cells, consist of proliferating c-Kit positive cells primarily in their core and differentiating cells expressing cardiac and endothelial cell markers on their periphery. Although the intracardiac origin of adult myocytes has been unequivocally documented, the potential of an extracardiac source of cells, able to repopulate the lost CSCs in pathological conditions (infarct) cannot be excluded and will be discussed in this review. The delivery of human CSs or of CSs-derived cells into the injured heart of the SCID mouse resulted in engraftment, migration, myocardial regeneration and improvement of left ventricular function. Our method for ex vivo expansion of resident CSCs for subsequent autologous transplantation back into the heart, may give these cell populations, the resident and the transplanted one, the combined ability to mediate myocardial regeneration to an appreciable degree, and may change the way in which cardiovascular disease will be approached in the future.}, } @article {pmid17627471, year = {2007}, author = {Fisher, SA and Burggren, WW}, title = {Role of hypoxia in the evolution and development of the cardiovascular system.}, journal = {Antioxidants & redox signaling}, volume = {9}, number = {9}, pages = {1339-1352}, doi = {10.1089/ars.2007.1704}, pmid = {17627471}, issn = {1523-0864}, support = {R01 HL65314/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Basal Metabolism ; Body Weight ; *Cardiovascular Physiological Phenomena ; *Evolution, Molecular ; Female ; Humans ; *Hypoxia ; Mammals ; Oxygen Consumption ; Placenta/physiology ; Pregnancy ; Vertebrates ; }, abstract = {How multicellular organisms obtain and use oxygen and other substrates has evolved over hundreds of millions of years in parallel with the evolution of oxygen-delivery systems. A steady supply of oxygen is critical to the existence of organisms that depend on oxygen as a primary source of fuel (i.e., those that live by aerobic metabolism). Not surprisingly, a number of mechanisms have evolved to defend against oxygen deprivation. This review highlights evolutionary and developmental aspects of O2 delivery to allow understanding of adaptive responses to O2 deprivation (hypoxia). First, we consider how the drive for more efficient oxygen delivery from the heart to the periphery may have shaped the evolution of the cardiovascular system, with particular attention to the routing of oxygenated and deoxygenated blood in the cardiac outlet. Then we consider the role of O2 in the morphogenesis of the cardiovascular system of animals of increasing size and complexity. We conclude by suggesting areas for future research regarding the role of oxygen deprivation and oxidative stress in the normal development of the heart and vasculature or in the pathogenesis of congenital heart defects.}, } @article {pmid17627470, year = {2007}, author = {Webster, KA}, title = {Hypoxia: life on the edge.}, journal = {Antioxidants & redox signaling}, volume = {9}, number = {9}, pages = {1303-1307}, doi = {10.1089/ars.2007.1730}, pmid = {17627470}, issn = {1523-0864}, support = {HL072924/HL/NHLBI NIH HHS/United States ; HL44578/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Cell Death ; Homeostasis ; Humans ; Hyperoxia/physiopathology ; Hypoxia/*physiopathology ; Reactive Oxygen Species ; }, abstract = {Hypoxia and its corollaries pose both negative and positive pressures to multicellular eukaryotes. Evolutionarily, life developed under hypoxia, and the building blocks were established under conditions close to anaerobiosis; therefore, reason exists to expect that certain biologic processes may perform preferentially under hypoxia. Evolving evidence suggests that by providing an environment of reduced oxidative stress, hypoxia may help preserve the biologic functions of some cells and prevent senescence. Hypoxia provides essential signals for development, trimming redundant tissue by inducing apoptosis and driving the growth and development of oxygen and nutrient delivery systems, as well as those for waste management. The pathologic consequences of hypoxia and ischemia, including acidosis and oxidative stress associated with hypoxia-reoxygenation, form the basis of most of the major diseases confronting humans, including heart disease, cancer, and age-related degenerative conditions. The 11 articles in the forum touch on multiple aspects of hypoxia, in particular, signaling responses, adaptations, and diseases that result from imbalance and fluctuations of supply and demand. Although we have developed elaborate processes to combat hypoxia and oxidative damage, it is clear that oxygen and our environment still control us, perhaps even more than they did our unicellular ancestors 2 billion years ago.}, } @article {pmid17622536, year = {2007}, author = {Zhu, XY and Zhao, M and Ma, S and Ge, YM and Zhang, MF and Chen, LP}, title = {Induction and origin of adventitious shoots from chimeras of Brassica juncea and Brassica oleracea.}, journal = {Plant cell reports}, volume = {26}, number = {10}, pages = {1727-1732}, pmid = {17622536}, issn = {0721-7714}, mesh = {Brassica/*growth & development ; Chimera/*growth & development ; Meristem/*growth & development ; Mustard Plant/*growth & development ; }, abstract = {The chimeras between tuber mustard (Brassica juncea) and red cabbage (B. oleracea) were artificially synthesized in our previous study. Adventitious shoots were induced from nodal segments and leaf discs of TCC (LI-LII-LIII, LI -the outmost layer of shoot apical meristem; LII -the middle layer; LIII -the innermost layer. T = Tuber mustard, C = Red cabbage) chimeras. The origin of the shoots was analyzed by histology and molecular biology. As a result, the frequency of adventitious shoot induction rose with the increase of BA in MS medium in the area of the nodes. However, there was no different induction frequency of adventitious shoots from nodal segment bases in media with different BA concentrations. Most adventitious shoots (clustered shoots) arising from the node area were TTT (Tuber mustard- Tuber mustard- Tuber mustard) and only 4 shoots were chimeras, which indicated that more shoots originated from LI than from LII and LIII. All shoots from nodal segment bases were CCC (Red cabbage-Red cabbage- Red cabbage), indicating that the shoots originated from LII or LII and LIII. There were significant differences in the regeneration rate in the margin of the leaf discs among the three combinations of BA and NAA. Most adventitious shoots from the margin of leaf discs were CCC but 2 out of 70 were chimeras, which indicated that more shoots originated from LII or LII and LIII than from LI. All chimeras obtained by regeneration were different from the original explant donor in type in the present study. The origin of the adventitious shoots varied with the site of origin on the donor plant, and could be multicellular and multihistogenic.}, } @article {pmid17608793, year = {2007}, author = {Brüssow, H}, title = {Bacteria between protists and phages: from antipredation strategies to the evolution of pathogenicity.}, journal = {Molecular microbiology}, volume = {65}, number = {3}, pages = {583-589}, doi = {10.1111/j.1365-2958.2007.05826.x}, pmid = {17608793}, issn = {0950-382X}, mesh = {Bacteria/*pathogenicity ; Bacteriophages/*physiology ; *Biological Evolution ; }, abstract = {Bacteriophages and protists are major causes of bacterial mortality. Genomics suggests that phages evolved well before eukaryotic protists. Bacteria were thus initially only confronted with phage predators. When protists evolved, bacteria were caught between two types of predators. One successful antigrazing strategy of bacteria was the elaboration of toxins that would kill the grazer. The released cell content would feed bystander bacteria. I suggest here that, to fight grazing protists, bacteria teamed up with those phage predators that concluded at least a temporary truce with them in the form of lysogeny. Lysogeny was perhaps initially a resource management strategy of phages that could not maintain infection chains. Subsequently, lysogeny might have evolved into a bacterium-prophage coalition attacking protists, which became a food source for them. When protists evolved into multicellular animals, the lysogenic bacteria tracked their evolving food source. This hypothesis could explain why a frequent scheme of bacterial pathogenicity is the survival in phagocytes, why a significant fraction of bacterial pathogens have prophage-encoded virulence genes, and why some virulence factors of animal pathogens are active against unicellular eukaryotes. Bacterial pathogenicity might thus be one playing option of the stone-scissor-paper game played between phages-bacteria-protists, with humans getting into the crossfire.}, } @article {pmid17596296, year = {2007}, author = {Choe, KP and Strange, K}, title = {Evolutionarily conserved WNK and Ste20 kinases are essential for acute volume recovery and survival after hypertonic shrinkage in Caenorhabditis elegans.}, journal = {American journal of physiology. Cell physiology}, volume = {293}, number = {3}, pages = {C915-27}, doi = {10.1152/ajpcell.00126.2007}, pmid = {17596296}, issn = {0363-6143}, mesh = {Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/enzymology/*genetics ; Caenorhabditis elegans Proteins/*genetics/metabolism ; Evolution, Molecular ; Germinal Center Kinases ; Green Fluorescent Proteins/genetics ; Intestines/enzymology ; Molecular Sequence Data ; Osmotic Pressure ; Phylogeny ; Protein Kinases/*genetics/metabolism ; Protein Serine-Threonine Kinases/*genetics/metabolism ; RNA Interference ; Saline Solution, Hypertonic/pharmacology ; Subcutaneous Tissue/enzymology ; WNK Lysine-Deficient Protein Kinase 1 ; Water-Electrolyte Balance/*physiology ; }, abstract = {Members of the germinal center kinase (GCK)-VI subfamily of Ste20 kinases regulate a Caenorhabditis elegans ClC anion channel and vertebrate SLC12 cation-Cl(-) cotransporters. With no lysine (K) (WNK) protein kinases interact with and activate the mammalian GCK-VI kinases proline-alanine-rich Ste20-related kinase (PASK) and oxidative stress-responsive 1 (OSR1). We demonstrate here for the first time that GCK-VI kinases play an essential role in whole animal osmoregulation. RNA interference (RNAi) knockdown of the single C. elegans GCK-VI kinase, GCK-3, dramatically inhibits systemic volume recovery and survival after hypertonic shrinkage. Tissue-specific RNAi suggests that GCK-3 functions primarily in the hypodermis and intestine to mediate volume recovery. The single C. elegans WNK kinase, WNK-1, binds to GCK-3, and wnk-1 knockdown gives rise to a phenotype qualitatively similar to that of gck-3(RNAi) worms. Knockdown of the two kinases together has no additive effect, suggesting that WNK-1 and GCK-3 function in a common pathway. We postulate that WNK-1 functions upstream of GCK-3 in a manner similar to that postulated for its mammalian homologs. Phylogenetic analysis of kinase functional domains suggests that the interaction between GCK-VI and WNK kinases first occurred in an early metazoan and therefore likely coincided with the need of multicellular animals to tightly regulate transepithelial transport processes that mediate systemic osmotic homeostasis.}, } @article {pmid17592819, year = {2007}, author = {Bennici, A}, title = {Unresolved problems on the origin and early evolution of land plants.}, journal = {Rivista di biologia}, volume = {100}, number = {1}, pages = {55-67}, pmid = {17592819}, issn = {0035-6050}, mesh = {*Biological Evolution ; *Origin of Life ; *Plants ; }, abstract = {The origin of land plants or embryophytes from the Charophyceae is generally accepted today by the botanists. In fact, numerous morphological, cytological, ultrastructural, biochemical and molecular characters are shared in these organisms. A fundamental problem is still constituted by the evolution of the sporophyte, i.e. the appearance of two different phase cycles (gametophyte/sporophyte alternance), although two theories ("antithetic" and "homologous") try to explain this evolutionary event.However, another phylogenetic dilemma is represented, in my opinion, either by the formation of bryophytes or by the transition from these first land plants to the pteridophytes, considering them at whole organism level. The bryophyte gametophyte is the most elaborate of the land plants. It presents several complex characters, principally the growth developmental form, the appearance of multicellular sex organs, antheridia and archegonia. Also the sporophyte shows a complicated structure that is not found in the other land plants or tracheophytes. The sporangium, in particular, exhibits some intricate morphological traits such as the peristome of true mosses for spore dispersion, the elaters of liverworts and the indeterminate growth in the hornworts. The pteridophytes are represented especially by their dominant sporophyte. This latter has the capacity to produce multiple sporangia and, in many cases, two kinds of spores which develop in male and female gametophyte (heterosporous pteridophytes). Another important characteristic of this sporophyte is its ability to become independent of the gametophyte. However, one of the most innovative character is the formation of true vascular elements (xylem and phloem). All these very large evolutionary jumps are discussed on the basis of the phyletic gradualistic neo-Darwinian theory and the punctuated equilibrium theory of Eldredge and Gould. In this context other genetic evolutionary mechanisms are also considered.Nevertheless, the origin of bryophytes and pteridophytes remain, at the moment, a mystery.}, } @article {pmid17589782, year = {2007}, author = {Hall, SH and Yenugu, S and Radhakrishnan, Y and Avellar, MC and Petrusz, P and French, FS}, title = {Characterization and functions of beta defensins in the epididymis.}, journal = {Asian journal of andrology}, volume = {9}, number = {4}, pages = {453-462}, doi = {10.1111/j.1745-7262.2007.00298.x}, pmid = {17589782}, issn = {1008-682X}, support = {D43TW/HD00627/HD/NICHD NIH HHS/United States ; R37-HD04466/HD/NICHD NIH HHS/United States ; U54-HD35041/HD/NICHD NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Antigens, Surface/chemistry/genetics/physiology ; Chromosome Mapping ; Conserved Sequence ; Epididymis/*physiology ; Evolution, Molecular ; Glycopeptides/chemistry/genetics/physiology ; Humans ; Male ; Mammals ; Models, Molecular ; Molecular Sequence Data ; Primates ; Protein Conformation ; beta-Defensins/genetics/*physiology ; }, abstract = {The epididymal beta-defensins have evolved by repeated gene duplication and divergence to encode a family of proteins that provide direct protection against pathogens and also support the male reproductive tract in its primary function. Male tract defensins also facilitate recovery from pathogen attack. The beta-defensins possess ancient conserved sequence and structural features widespread in multi-cellular organisms, suggesting fundamental roles in species survival. Primate SPAG11, the functional fusion of two ancestrally independent beta-defensin genes, produces a large family of alternatively spliced transcripts that are expressed according to tissue-specific and species-specific constraints. The complexity of SPAG11 varies in different branches of mammalian evolution. Interactions of human SPAG11D with host proteins indicate involvement in multiple signaling pathways.}, } @article {pmid17588271, year = {2007}, author = {Itoh, M and Nacher, JC and Kuma, K and Goto, S and Kanehisa, M}, title = {Evolutionary history and functional implications of protein domains and their combinations in eukaryotes.}, journal = {Genome biology}, volume = {8}, number = {6}, pages = {R121}, pmid = {17588271}, issn = {1474-760X}, mesh = {Animals ; Eukaryotic Cells/chemistry/metabolism ; *Evolution, Molecular ; Humans ; Phylogeny ; Prokaryotic Cells/chemistry/metabolism ; Protein Structure, Tertiary ; Proteins/*chemistry/*genetics ; Proteome ; }, abstract = {BACKGROUND: In higher multicellular eukaryotes, complex protein domain combinations contribute to various cellular functions such as regulation of intercellular or intracellular signaling and interactions. To elucidate the characteristics and evolutionary mechanisms that underlie such domain combinations, it is essential to examine the different types of domains and their combinations among different groups of eukaryotes.

RESULTS: We observed a large number of group-specific domain combinations in animals, especially in vertebrates. Examples include animal-specific combinations in tyrosine phosphorylation systems and vertebrate-specific combinations in complement and coagulation cascades. These systems apparently underwent extensive evolution in the ancestors of these groups. In extant animals, especially in vertebrates, animal-specific domains have greater connectivity than do other domains on average, and contribute to the varying number of combinations in each animal subgroup. In other groups, the connectivities of older domains were greater on average. To observe the global behavior of domain combinations during evolution, we traced the changes in domain combinations among animals and fungi in a network analysis. Our results indicate that there is a correlation between the differences in domain combinations among different phylogenetic groups and different global behaviors.

CONCLUSION: Rapid emergence of animal-specific domains was observed in animals, contributing to specific domain combinations and functional diversification, but no such trends were observed in other clades of eukaryotes. We therefore suggest that the strategy for achieving complex multicellular systems in animals differs from that of other eukaryotes.}, } @article {pmid17583495, year = {2007}, author = {Cahill, MA}, title = {Progesterone receptor membrane component 1: an integrative review.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {105}, number = {1-5}, pages = {16-36}, doi = {10.1016/j.jsbmb.2007.02.002}, pmid = {17583495}, issn = {0960-0760}, mesh = {Animals ; Cloning, Molecular ; Humans ; Membrane Proteins/chemistry/genetics/*physiology ; Protein Binding ; Protein Conformation ; Receptors, Progesterone/chemistry/genetics/*physiology ; Subcellular Fractions/metabolism ; }, abstract = {Progesterone receptor membrane component 1 (PGRMC1) contains a cytochrome b5 domain fold and belongs to the so-called membrane-associated progesterone receptor (MAPR) protein family that is widespread in eukaryotes. PGRMC1 and the related PGRMC2 mammalian family member diverged sometime after the evolution of segmented metazoan body plan and the appearance of vertebrates. Therefore PGRMC1 might be expected to be involved in some ancient eukaryotic processes, as well as more modern functions related to multicellularity and tissue interactions. Perhaps this explains the perplexing diversity of contexts where PGRMC1 has been observed, apparently being involved in different cellular processes at various sub-cellular locations. This review attempts to collate and interpret these observations. Ironically, despite being the archetypal member of the MAPR family, it has yet to be demonstrated that PGRMC1 exhibits specific progesterone binding. Potential roles of heme and steroid/sterol ligands are reviewed, as well as the implications of apparent target sequences within PGRMC1 for binding by SH2- and SH3-domain proteins as well as kinases. These motifs are modelled using the cytochrome b5 domain NMR structure of the Arabidopsis protein 1J03, implicating a possible function for PGRMC1 as an adaptor protein involved in regulating protein interactions and intracellular signal transduction and/or membrane trafficking. This interpretation is supported by the apparent presence of immunoreceptor tyrosine-based activation motif/ITAM sequences that are involved in endocytosis and vesicle targeting, and the colocalisation of PGRMC1 with caveolin and at the cytoplasmic membrane. Evidence for roles in disease, especially cancer, is also discussed.}, } @article {pmid17576077, year = {2007}, author = {Jaramillo, MA and Kramer, EM}, title = {Molecular evolution of the petal and stamen identity genes, APETALA3 and PISTILLATA, after petal loss in the Piperales.}, journal = {Molecular phylogenetics and evolution}, volume = {44}, number = {2}, pages = {598-609}, doi = {10.1016/j.ympev.2007.03.015}, pmid = {17576077}, issn = {1055-7903}, mesh = {Amino Acid Sequence ; Arabidopsis/anatomy & histology/classification/genetics ; Aristolochia/anatomy & histology/classification/genetics ; Conserved Sequence ; *Evolution, Molecular ; Flowers/anatomy & histology/classification/*genetics ; Genes, Plant/*genetics ; MADS Domain Proteins/chemistry/classification/*genetics ; Magnoliopsida/anatomy & histology/classification/*genetics ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; }, abstract = {Organ loss is an evolutionary phenomenon commonly observed in all kinds of multicellular organisms. Across the angiosperms, petals have been lost several times over the course of their diversification. We examined the evolution of petal and stamen identity genes in the Piperales, a basal lineage of angiosperms that includes the perianthless (with no petals or sepals) families Piperaceae and Saururaceae as well as the Aristolochiaceae, which exhibit a well-developed perianth. Here, we provide evidence for relaxation of selection on the putative petal and stamen identity genes, homologs of APETALA3 and PISTILLATA, following the loss of petals in the Piperales. Our results are particularly interesting as the B-class genes are not only responsible for the production of petals but are also central to stamen identity, the male reproductive organs that show no modification in these plants. Relaxed purifying selection after the loss of only one of these organs suggests that there has been dissociation of the functional roles of these genes in the Piperales.}, } @article {pmid17563079, year = {2007}, author = {Schaap, P}, title = {Evolution of size and pattern in the social amoebas.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {29}, number = {7}, pages = {635-644}, pmid = {17563079}, issn = {0265-9247}, support = {BB/D013453/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amoebida/cytology/*growth & development/metabolism ; Animals ; *Biological Evolution ; Cyclic AMP/metabolism ; Models, Biological ; }, abstract = {A fundamental goal of biology is to understand how novel phenotypes evolved through changes in existing genes. The Dictyostelia or social amoebas represent a simple form of multicellularity, where starving cells aggregate to build fruiting structures. This review summarizes efforts to provide a framework for investigating the genetic changes that generated novel morphologies in the Dictyostelia. The foundation is a recently constructed molecular phylogeny of the Dictyostelia, which was used to examine trends in the evolution of novel forms and in the divergence of genes that shape these forms. There is a major trend towards the formation of large unbranched fruiting bodies, which is correlated with the use of cyclic AMP (cAMP) as a secreted signal to coordinate cell aggregation. The role of cAMP in aggregation arose through co-option of a pathway that originally acted to coordinate fruiting body formation. The genotypic changes that caused this innovation and the role of dynamic cAMP signaling in defining fruiting body size and pattern throughout social amoeba evolution are discussed.}, } @article {pmid17561961, year = {2007}, author = {Päri, M and Kuusksalu, A and Lopp, A and Reintamm, T and Justesen, J and Kelve, M}, title = {Expression and characterization of recombinant 2',5'-oligoadenylate synthetase from the marine sponge Geodia cydonium.}, journal = {The FEBS journal}, volume = {274}, number = {13}, pages = {3462-3474}, doi = {10.1111/j.1742-4658.2007.05878.x}, pmid = {17561961}, issn = {1742-464X}, mesh = {2',5'-Oligoadenylate Synthetase/*chemistry ; Animals ; Chromatography ; Chromatography, High Pressure Liquid ; DNA, Complementary/metabolism ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli/metabolism ; Evolution, Molecular ; *Gene Expression Regulation ; Histidine/chemistry ; Porifera ; RNA/chemistry ; Recombinant Proteins/chemistry/*genetics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Time Factors ; }, abstract = {2',5'-oligoadenylate (2-5A) synthetases are known as components of the interferon-induced cellular defence mechanism in mammals. The existence of 2-5A synthetases in the evolutionarily lowest multicellular animals, the marine sponges, has been demonstrated and the respective candidate genes from Geodia cydonium and Suberites domuncula have been identified. In the present study, the putative 2-5A synthetase cDNA from G. cydonium was expressed in an Escherichia coli expression system to characterize the enzymatic activity of the recombinant polypeptide. Our studies reveal that, unlike the porcine recombinant 2-5A synthetase, the sponge recombinant protein associates strongly with RNA from E. coli, forming a heterogeneous set of complexes. No complete dissociation of the complex occurs during purification of the recombinant protein and the RNA constituent is partially protected from RNase degradation. We demonstrate that the sponge recombinant 2-5A synthetase in complex with E. coli RNA catalyzes the synthesis of 2',5'-phosphodiester-linked 5'-triphosphorylated oligoadenylates from ATP, although with a low specific activity. Poly(I).poly(C), an efficient artificial activator of the mammalian 2-5A synthetases, has only a minimal effect (an approximate two-fold increase) on the sponge recombinant 2-5A synthetase/bacterial RNA complex activity.}, } @article {pmid17551050, year = {2007}, author = {Abreu, F and Martins, JL and Silveira, TS and Keim, CN and de Barros, HGPL and Filho, FJG and Lins, U}, title = {'Candidatus Magnetoglobus multicellularis', a multicellular, magnetotactic prokaryote from a hypersaline environment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {57}, number = {Pt 6}, pages = {1318-1322}, doi = {10.1099/ijs.0.64857-0}, pmid = {17551050}, issn = {1466-5026}, mesh = {Bacterial Adhesion ; Brazil ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Deltaproteobacteria/*classification/cytology/*isolation & purification/physiology ; Flagella/physiology ; Genes, rRNA ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Molecular Sequence Data ; Phylogeny ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; }, abstract = {Phylogenetic analysis and phenotypic characterization were used to assign a multicellular magnetotactic prokaryote the name 'Candidatus Magnetoglobus multicellularis'. 'Candidatus Magnetoglobus multicellularis' lives in a large hypersaline coastal lagoon from Brazil and has properties that are unique among prokaryotes. It consists of a compact assembly or aggregate of flagellated bacterial cells, highly organized in a sphere, that swim in either helical or straight trajectories. The life cycle of 'Candidatus Magnetoglobus multicellularis' is completely multicellular, in which one aggregate grows by enlarging the size of its cells and approximately doubling the volume of the whole organism. Cells then divide synchronously, maintaining the spherical arrangement; finally the cells separate into two identical aggregates. Phylogenetic 16S rRNA gene sequence analysis showed that 'Candidatus Magnetoglobus multicellularis' is related to the dissimilatory sulfate-reducing bacteria within the Deltaproteobacteria and to other previously described, but not yet well characterized, multicellular magnetotactic prokaryotes.}, } @article {pmid17544809, year = {2007}, author = {Dodds, AW and Matsushita, M}, title = {The phylogeny of the complement system and the origins of the classical pathway.}, journal = {Immunobiology}, volume = {212}, number = {4-5}, pages = {233-243}, doi = {10.1016/j.imbio.2006.11.009}, pmid = {17544809}, issn = {0171-2985}, mesh = {Animals ; Complement Pathway, Classical/*immunology ; Complement System Proteins/classification/genetics/*immunology/metabolism ; Humans ; Lectins/metabolism ; *Phylogeny ; }, abstract = {The origins of the complement system have now been traced to near to the beginnings of multi-cellular animal life. Most of the evidence points to the earliest activation mechanism having been more similar to the lectin pathway than to the alternative pathway. C1q, the immunoglobulin recognition molecule of the classical pathway of the vertebrates, has now been shown to predate the development of antibody as it has been found in the lamprey, a jawless fish that lacks an acquired immune system. In this species, C1q acts as a lectin that binds MASPs and activates the C3/C4-like thioester protein of the lamprey complement system. The classical pathway can, therefore, be regarded as a specialised arm of the lectin pathway in which the specificity of C1q for carbohydrate has been recruited to recognise the Fc region of immunoglobulin.}, } @article {pmid17540861, year = {2007}, author = {Jackson, DJ and Macis, L and Reitner, J and Degnan, BM and Wörheide, G}, title = {Sponge paleogenomics reveals an ancient role for carbonic anhydrase in skeletogenesis.}, journal = {Science (New York, N.Y.)}, volume = {316}, number = {5833}, pages = {1893-1895}, doi = {10.1126/science.1141560}, pmid = {17540861}, issn = {1095-9203}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Bicarbonates/metabolism ; *Calcification, Physiologic ; Calcium Carbonate/analysis/metabolism ; Carbonic Anhydrases/chemistry/*genetics/*metabolism ; Computational Biology ; Evolution, Molecular ; Gene Duplication ; Genes ; Genomics ; Molecular Sequence Data ; Porifera/anatomy & histology/enzymology/*genetics/*physiology ; Recombinant Proteins/chemistry/metabolism ; }, abstract = {Sponges (phylum Porifera) were prolific reef-building organisms during the Paleozoic and Mesozoic approximately 542 to 65 million years ago. These ancient animals inherited components of the first multicellular skeletogenic toolkit from the last common ancestor of the Metazoa. Using a paleogenomics approach, including gene- and protein-expression techniques and phylogenetic reconstruction, we show that a molecular component of this toolkit was the precursor to the alpha-carbonic anhydrases (alpha-CAs), a gene family used by extant animals in a variety of fundamental physiological processes. We used the coralline demosponge Astrosclera willeyana, a "living fossil" that has survived from the Mesozoic, to provide insight into the evolution of the ability to biocalcify, and show that the alpha-CA family expanded from a single ancestral gene through several independent gene-duplication events in sponges and eumetazoans.}, } @article {pmid17538623, year = {2007}, author = {Molnár, A and Schwach, F and Studholme, DJ and Thuenemann, EC and Baulcombe, DC}, title = {miRNAs control gene expression in the single-cell alga Chlamydomonas reinhardtii.}, journal = {Nature}, volume = {447}, number = {7148}, pages = {1126-1129}, doi = {10.1038/nature05903}, pmid = {17538623}, issn = {1476-4687}, mesh = {Animals ; Base Sequence ; Chlamydomonas reinhardtii/*cytology/*genetics ; Evolution, Molecular ; *Gene Expression Regulation ; MicroRNAs/genetics/*metabolism ; RNA, Algal/genetics/*metabolism ; RNA, Protozoan/genetics/*metabolism ; }, abstract = {MicroRNAs (miRNAs) in eukaryotes guide post-transcriptional regulation by means of targeted RNA degradation and translational arrest. They are released by a Dicer nuclease as a 21-24-nucleotide RNA duplex from a precursor in which an imperfectly matched inverted repeat forms a partly double-stranded region. One of the two strands is then recruited by an Argonaute nuclease that is the effector protein of the silencing mechanism. Short interfering RNAs (siRNAs), which are similar to miRNAs, are also produced by Dicer but the precursors are perfectly double-stranded RNA. These siRNAs guide post-transcriptional regulation, as with miRNAs, and epigenetic genome modification. Diverse eukaryotes including fungi, plants, protozoans and metazoans produce siRNAs but, until now, miRNAs have not been described in unicellular organisms and it has been suggested that they evolved together with multicellularity in separate plant and animal lineages. Here we show that the unicellular alga Chlamydomonas reinhardtii contains miRNAs, putative evolutionary precursors of miRNAs and species of siRNAs resembling those in higher plants. The common features of miRNAs and siRNAs in an alga and in higher plants indicate that complex RNA-silencing systems evolved before multicellularity and were a feature of primitive eukaryotic cells.}, } @article {pmid17534075, year = {2007}, author = {Maizels, R}, title = {Regulation of the immune system in metazoan parasite infections.}, journal = {Novartis Foundation symposium}, volume = {281}, number = {}, pages = {192-204; discussion 204-9}, doi = {10.1002/9780470062128.ch16}, pmid = {17534075}, issn = {1528-2511}, mesh = {Animals ; *Biological Evolution ; Host-Parasite Interactions ; Humans ; Immunity, Innate/*genetics/immunology ; Interleukin-10/immunology ; Parasites/*immunology ; Parasitic Diseases/genetics/*immunology ; *Polymorphism, Genetic ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Eukaryotic, multicellular parasites such as the helminth worms have a major impact on the mammalian immune system in two contexts. First, they have evolved sophisticated strategies for long-term immune evasion including recruiting natural suppressive mechanisms such as the regulatory T cell (Tregs). Tregs play a role not only in repressing immunity to parasites, but also in dampening bystander responses such as those to allergens. To achieve these effects, they produce a range of immunomodulators some of which are evolutionary homologues of immune system cytokines, while others are novel proteins capable of interfering with immune cell signalling and differentiation. The second context in which metazoa may have influenced their host is at the level of genetic polymorphism in immune response genes. Alleles at loci originally associated with predisposition to asthma have more recently been found to confer heightened resistance to helminth parasites. This may suggest a mechanistic link between more vigorous type 2 responses in both allergy and infection. On a broader perspective, one may speculate that alleles advantageous in the historical environment of prevalent infection, now display a deleterious phenotype in our more 'hygienic' societies.}, } @article {pmid17532650, year = {2007}, author = {Jiang, DM and Wu, ZH and Zhao, JY and Li, YZ}, title = {Fruiting and non-fruiting myxobacteria: a phylogenetic perspective of cultured and uncultured members of this group.}, journal = {Molecular phylogenetics and evolution}, volume = {44}, number = {2}, pages = {545-552}, doi = {10.1016/j.ympev.2007.04.004}, pmid = {17532650}, issn = {1055-7903}, mesh = {Base Sequence ; Genes, Bacterial/genetics ; Microbial Viability ; Myxococcales/*classification/cytology/*genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The diversity of myxobacteria present in campus garden soil was surveyed by both cultivation-based and cultivation-independent methods. Detailed phylogenetic analysis of cultured and uncultured myxobacteria 16S rRNA gene sequences revealed that many undescribed relatives of the myxobacteria exist in nature. Molecular systematic analyses also revealed that myxobacterial genera described to date on the basis of the morphology of multi-cellular fruiting bodies were mostly monophyletic. However, these known taxa comprised only in a small part of the sequences recovered directly from soil in a cultivation-independent approach, indicating that the group is much more diverse than previously thought. We propose that the myxobacteria exist in two forms: the fruiting and the non-fruiting types. Most of the uncultured myxobacteria may represent taxa which rarely form fruiting bodies, or may lack some or all of the developmental genes needed for fruiting body formation. In order to identify non-fruiting myxobacteria, new morphology-independent cultivation and isolation techniques need to be developed.}, } @article {pmid17514203, year = {2007}, author = {Litman, GW and Cooper, MD}, title = {Why study the evolution of immunity?.}, journal = {Nature immunology}, volume = {8}, number = {6}, pages = {547-548}, pmid = {17514203}, issn = {1529-2908}, support = {R01 AI023338/AI/NIAID NIH HHS/United States ; R01 AI023338-23/AI/NIAID NIH HHS/United States ; R01 AI057559/AI/NIAID NIH HHS/United States ; R01 AI057559-04/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Humans ; Immune System/*immunology/*metabolism ; Immunity, Innate/immunology ; }, abstract = {Investigations of immune recognition in nonmammalian species provide new insights into the evolution of immunity and the inner workings of the mammalian immune system. Very diverse mechanisms are used by different multicellular organisms to recognize and cope with the rapidly evolving microbial world.}, } @article {pmid17509723, year = {2007}, author = {Toth, AL and Robinson, GE}, title = {Evo-devo and the evolution of social behavior.}, journal = {Trends in genetics : TIG}, volume = {23}, number = {7}, pages = {334-341}, doi = {10.1016/j.tig.2007.05.001}, pmid = {17509723}, issn = {0168-9525}, mesh = {Animals ; Ants ; Bees ; *Behavior, Animal ; Developmental Biology ; Endocrine System/metabolism ; Evolution, Molecular ; Genetics, Population ; Genome ; Models, Genetic ; Phenotype ; Phylogeny ; Selection, Genetic ; *Social Behavior ; }, abstract = {The integration of evolutionary biology with developmental genetics into the hybrid field of 'evo-devo' resulted in major advances in understanding multicellular development and morphological evolution. Here we show how insights from evo-devo can be applied to study the evolution of social behavior. We develop this idea by reviewing studies that suggest that molecular pathways controlling feeding behavior and reproduction in solitary insects are part of a 'genetic toolkit' underlying the evolution of a particularly complex form of social behavior, division of labor among workers in honeybee colonies. The evo-devo approach, coupled with advances in genomics for non-model genetic organisms, including the recent sequencing of the honeybee genome, promises to advance our understanding of the evolution of social behavior.}, } @article {pmid17501745, year = {2007}, author = {Derelle, R and Lopez, P and Le Guyader, H and Manuel, M}, title = {Homeodomain proteins belong to the ancestral molecular toolkit of eukaryotes.}, journal = {Evolution & development}, volume = {9}, number = {3}, pages = {212-219}, doi = {10.1111/j.1525-142X.2007.00153.x}, pmid = {17501745}, issn = {1520-541X}, mesh = {Animals ; Eukaryota/physiology ; *Evolution, Molecular ; Fungi/physiology ; Homeodomain Proteins/*metabolism ; Plants/metabolism ; }, abstract = {Multicellular organization arose several times by convergence during the evolution of eukaryotes (e.g., in terrestrial plants, several lineages of "algae," fungi, and metazoans). To reconstruct the evolutionary transitions between unicellularity and multicellularity, we need a proper understanding of the origin and diversification of regulatory molecules governing the construction of a multicellular organism in these various lineages. Homeodomain (HD) proteins offer a paradigm for studying such issues, because in multicellular eukaryotes, like animals, fungi and plants, these transcription factors are extensively used in fundamental developmental processes and are highly diversified. A number of large eukaryote lineages are exclusively unicellular, however, and it remains unclear to what extent this condition reflects their primitive lack of "good building blocks" such as the HD proteins. Taking advantage from the recent burst of sequence data from a wide variety of eukaryote taxa, we show here that HD-containing transcription factors were already existing and diversified (in at least two main classes) in the last common eukaryote ancestor. Although the family was retained and independently expanded in the multicellular taxa, it was lost in several lineages of unicellular parasites or intracellular symbionts. Our findings are consistent with the idea that the common ancestor of eukaryotes was complex in molecular terms, and already possessed many of the regulatory molecules, which later favored the multiple convergent acquisition of multicellularity.}, } @article {pmid17498550, year = {2007}, author = {Salipante, SJ and Horwitz, MS}, title = {A phylogenetic approach to mapping cell fate.}, journal = {Current topics in developmental biology}, volume = {79}, number = {}, pages = {157-184}, doi = {10.1016/S0070-2153(06)79006-8}, pmid = {17498550}, issn = {0070-2153}, support = {R01DK58161/DK/NIDDK NIH HHS/United States ; T32GM007266/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biomarkers/metabolism ; Cell Division/physiology ; *Cell Lineage ; Cells, Cultured ; Chimera/physiology ; Embryo, Mammalian/*cytology ; *Embryo, Nonmammalian ; Genetic Engineering ; *Morphogenesis ; Mutation ; *Phylogeny ; }, abstract = {Recent, surprising, and controversial discoveries have challenged conventional concepts regarding the origins and plasticity of stem cells, and their contributions to tissue regeneration, and highlight just how little is known about mammalian development in comparison to simpler model organisms. In the case of the transparent worm, Caenorhabditis elegans, Sulston and colleagues used a microscope to record the birth and death of every cell during its life, and the compilation of this "fate map" represents a milestone achievement of developmental biology. Determining a fate map for mammals or other higher organisms is more complicated because they are opaque, take a long time to mature, and have a tremendous number of cells. Consequently, fate mapping experiments have relied on tagging a progenitor cell with a dye or genetic marker in order to later identify its descendants. This approach, however, extracts little information because it demonstrates that a population of cells, all having inherited the same label, shares a common ancestor, but it does not reveal how cells in that population are related to one another. To avoid that problem, as well as technical limitations of current methods for mapping cell fate, we, and others, have developed a new strategy for retrospectively deriving cell fate maps by using phylogenetics to infer the order in which somatic mutations have arisen in the genomes of individual cells during development in multicellular organisms. DNA replication inevitably introduces mutations, particularly at repetitive sequences, every time a cell divides. It is thus possible to deduce the history of cell divisions by cataloging somatic mutations and phylogenetically reconstructing cell lineage. This approach has the potential to produce a complete mammalian cell fate map that, in principle, could describe the developmental lineage of any cell and help resolve outstanding questions of stem cell biology, tissue repair and maintenance, and aging.}, } @article {pmid17496139, year = {2007}, author = {Gilbert, OM and Foster, KR and Mehdiabadi, NJ and Strassmann, JE and Queller, DC}, title = {High relatedness maintains multicellular cooperation in a social amoeba by controlling cheater mutants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {104}, number = {21}, pages = {8913-8917}, pmid = {17496139}, issn = {0027-8424}, support = {T15 LM007093/LM/NLM NIH HHS/United States ; 5T15 LM07093/LM/NLM NIH HHS/United States ; }, mesh = {Animals ; Dictyostelium/*genetics ; Evolution, Molecular ; F-Box Proteins/genetics/metabolism ; Mutant Chimeric Proteins/genetics ; Mutation/genetics ; Protozoan Proteins/genetics/metabolism ; }, abstract = {The control of cheating is important for understanding major transitions in evolution, from the simplest genes to the most complex societies. Cooperative systems can be ruined if cheaters that lower group productivity are able to spread. Kin-selection theory predicts that high genetic relatedness can limit cheating, because separation of cheaters and cooperators limits opportunities to cheat and promotes selection against low-fitness groups of cheaters. Here, we confirm this prediction for the social amoeba Dictyostelium discoideum; relatedness in natural wild groups is so high that socially destructive cheaters should not spread. We illustrate in the laboratory how high relatedness can control a mutant that would destroy cooperation at low relatedness. Finally, we demonstrate that, as predicted, mutant cheaters do not normally harm cooperation in a natural population. Our findings show how altruism is preserved from the disruptive effects of such mutant cheaters and how exceptionally high relatedness among cells is important in promoting the cooperation that underlies multicellular development.}, } @article {pmid17495008, year = {2007}, author = {Carmel, L and Wolf, YI and Rogozin, IB and Koonin, EV}, title = {Three distinct modes of intron dynamics in the evolution of eukaryotes.}, journal = {Genome research}, volume = {17}, number = {7}, pages = {1034-1044}, pmid = {17495008}, issn = {1088-9051}, mesh = {Algorithms ; Animals ; Decision Trees ; *Evolution, Molecular ; Introns/*genetics ; *Models, Genetic ; Multigene Family ; Probability ; Time ; }, abstract = {Several contrasting scenarios have been proposed for the origin and evolution of spliceosomal introns, a hallmark of eukaryotic genes. A comprehensive probabilistic model to obtain a definitive reconstruction of intron evolution was developed and applied to 391 sets of conserved genes from 19 eukaryotic species. It is inferred that a relatively high intron density was reached early, i.e., the last common ancestor of eukaryotes contained >2.15 introns/kilobase, and the last common ancestor of multicellular life forms harbored approximately 3.4 introns/kilobase, a greater intron density than in most of the extant fungi and in some animals. The rates of intron gain and intron loss appear to have been dropping during the last approximately 1.3 billion years, with the decline in the gain rate being much steeper. Eukaryotic lineages exhibit three distinct modes of evolution of the intron-exon structure. The primary, balanced mode, apparently, operates in all lineages. In this mode, intron gain and loss are strongly and positively correlated, in contrast to previous reports on inverse correlation between these processes. The second mode involves an elevated rate of intron loss and is prevalent in several lineages, such as fungi and insects. The third mode, characterized by elevated rate of intron gain, is seen only in deep branches of the tree, indicating that bursts of intron invasion occurred at key points in eukaryotic evolution, such as the origin of animals. Intron dynamics could depend on multiple mechanisms, and in the balanced mode, gain and loss of introns might share common mechanistic features.}, } @article {pmid17494762, year = {2007}, author = {Moran, NA}, title = {Symbiosis as an adaptive process and source of phenotypic complexity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {104 Suppl 1}, number = {Suppl 1}, pages = {8627-8633}, pmid = {17494762}, issn = {0027-8424}, mesh = {Adaptation, Biological/*physiology ; Animals ; Bacteria/genetics/virology ; Bacteriophages/genetics/physiology ; Biological Evolution ; Eukaryotic Cells/physiology ; Gene Transfer, Horizontal ; Genetic Vectors ; Genome/genetics ; Insecta/genetics/physiology ; *Phenotype ; Symbiosis/genetics/*physiology ; }, abstract = {Genomics has revealed that inheritance systems of separate species are often not well segregated: genes and capabilities that evolve in one lineage are often stably acquired by another lineage. Although direct gene transfer between species has occurred at some level in all major groups, it appears to be far more frequent in prokaryotes than in multicellular eukaryotes. An alternative to incorporating novel genes into a recipient genome is acquiring a stable, possibly heritable, symbiotic association and thus enjoying benefits of complementary metabolic capabilities. These kinds of symbioses have arisen frequently in animals; for example, many insect groups have diversified on the basis of symbiotic associations acquired early in their evolutionary histories. The resulting associations are highly complex, often involving specialized cell types and organs, developmental mechanisms that ensure transfer of symbionts between generations, and mechanisms for controlling symbiont proliferation and location. The genomes of long-term obligate symbionts often undergo irreversible gene loss and deterioration even as hosts evolve dependence on them. In some cases, animal genomes may have acquired genes from symbionts, mirroring the gene uptake from mitochondrial and plastid genomes. Multiple symbionts often coexist in the same host, resulting in coadaptation among several phylogenetically distant genomes.}, } @article {pmid17494748, year = {2007}, author = {Michod, RE}, title = {Evolution of individuality during the transition from unicellular to multicellular life.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {104 Suppl 1}, number = {Suppl 1}, pages = {8613-8618}, pmid = {17494748}, issn = {0027-8424}, mesh = {*Biological Evolution ; Volvox/*cytology/*physiology ; }, abstract = {Individuality is a complex trait, yet a series of stages each advantageous in itself can be shown to exist allowing evolution to get from unicellular individuals to multicellular individuals. We consider several of the key stages involved in this transition: the initial advantage of group formation, the origin of reproductive altruism within the group, and the further specialization of cell types as groups increase in size. How do groups become individuals? This is the central question we address. Our hypothesis is that fitness tradeoffs drive the transition of a cell group into a multicellular individual through the evolution of cells specialized at reproductive and vegetative functions of the group. We have modeled this hypothesis and have tested our models in two ways. We have studied the origin of the genetic basis for reproductive altruism (somatic cells specialized at vegetative functions) in the multicellular Volvox carteri by showing how an altruistic gene may have originated through cooption of a life-history tradeoff gene present in a unicellular ancestor. Second, we ask why reproductive altruism and individuality arise only in the larger members of the volvocine group (recognizing that high levels of kinship are present in all volvocine algae groups). Our answer is that the selective pressures leading to reproductive altruism stem from the increasing cost of reproduction with increasing group size. Concepts from population genetics and evolutionary biology appear to be sufficient to explain complexity, at least as it relates to the problem of the major transitions between the different kinds of evolutionary individuals.}, } @article {pmid17492602, year = {2007}, author = {Meslin, B and Barnadas, C and Boni, V and Latour, C and De Monbrison, F and Kaiser, K and Picot, S}, title = {Features of apoptosis in Plasmodium falciparum erythrocytic stage through a putative role of PfMCA1 metacaspase-like protein.}, journal = {The Journal of infectious diseases}, volume = {195}, number = {12}, pages = {1852-1859}, doi = {10.1086/518253}, pmid = {17492602}, issn = {0022-1899}, mesh = {Amino Acid Sequence ; Animals ; Antimalarials/pharmacology ; Antineoplastic Agents, Phytogenic/pharmacology ; Apoptosis/*physiology ; COS Cells ; Caspases/genetics/*physiology ; Chlorocebus aethiops ; Chloroquine/pharmacology ; DNA Fragmentation ; Etoposide/pharmacology ; Hemagglutinins/metabolism ; Humans ; Membrane Potential, Mitochondrial/physiology ; Molecular Sequence Data ; Phylogeny ; Plasmodium falciparum/drug effects/genetics/*physiology ; Protein Structure, Tertiary ; Sequence Alignment ; Time Factors ; }, abstract = {The ability to undergo apoptosis, previously thought to be exclusive to multicellular organisms, has been demonstrated in unicellular parasites. On the basis of an observation that Plasmodium "crisis forms" were seen in vitro after cultivation in media containing an antimalarial drug, we attempted to determine whether Plasmodium falciparum has the ability to undergo apoptosis. By use of either the apoptosis-inducer etoposide or the antimalarial chloroquine, apoptosis in Plasmodium asexual stages was evident by the observation of DNA fragmentation and disruption of transmembrane mitochondrial potential. Next, we sought to determine whether Plasmodium produces specific cysteine proteases that can induce apoptosis. We hypothesized that the 2 metacaspase-like proteins present in the Plasmodium genome contained features typical of downstream execution steps and upstream signaling pathways such caspase activation and domain recruitment. We report that one of the metacaspase genes, PF13_0289, in addition to a universally conserved catalytic cysteine and histidine dyad required for catalysis activity, contains a putative caspase recruitment domain in the N-terminal amino acid sequence. This putative P. falciparum metacaspase protein has been designated PfMCA1. Our findings offer important insights into parasite survival strategies that could open new ways for therapeutic alternatives to drug resistance.}, } @article {pmid17470535, year = {2007}, author = {Zhao, T and Li, G and Mi, S and Li, S and Hannon, GJ and Wang, XJ and Qi, Y}, title = {A complex system of small RNAs in the unicellular green alga Chlamydomonas reinhardtii.}, journal = {Genes & development}, volume = {21}, number = {10}, pages = {1190-1203}, pmid = {17470535}, issn = {0890-9369}, mesh = {Animals ; Base Pairing ; Base Sequence ; *Biological Evolution ; Blotting, Northern ; Chlamydomonas reinhardtii/*genetics ; Computational Biology ; Gene Expression Profiling ; Gene Expression Regulation/*physiology ; Genomics/methods ; MicroRNAs/*physiology ; Molecular Sequence Data ; RNA Interference/*physiology ; RNA, Small Interfering/*physiology ; Sequence Analysis, DNA ; }, abstract = {Endogenous small RNAs function in RNA interference (RNAi) pathways to control gene expression through mRNA cleavage, translational repression, or chromatin modification. Plants and animals contain many microRNAs (miRNAs) that play vital roles in development, including helping to specify cell type and tissue identity. To date, no miRNAs have been reported in unicellular organisms. Here we show that Chlamydomonas reinhardtii, a unicellular green alga, encodes many miRNAs. We also show that a Chlamydomonas miRNA can direct the cleavage of its target mRNA in vivo and in vitro. We further show that the expression of some miRNAs/Candidates increases or decreases during Chlamydomonas gametogenesis. In addition to miRNAs, Chlamydomonas harbors other types of small RNAs including phased small interfering RNAs (siRNAs) that are reminiscent of plant trans-acting siRNAs, as well as siRNAs originating from protein-coding genes and transposons. Our findings suggest that the miRNA pathway and some siRNA pathways are ancient mechanisms of gene regulation that evolved prior to the emergence of multicellularity.}, } @article {pmid19069945, year = {2007}, author = {Ebrahimie, E and Hosseinzadeh, A and Nagavi, MR and Ghannadha, MR and Mohammadie-Dehcheshmeh, M}, title = {Combined direct regeneration protocols in tissue culture of different cumin genotypes based on pre-existing meristems.}, journal = {Pakistan journal of biological sciences : PJBS}, volume = {10}, number = {9}, pages = {1360-1370}, doi = {10.3923/pjbs.2007.1360.1370}, pmid = {19069945}, issn = {1028-8880}, mesh = {Benzyl Compounds ; Crops, Agricultural ; *Cuminum/anatomy & histology/genetics/physiology ; *Genotype ; Indoleacetic Acids/pharmacology ; Kinetin/pharmacology ; Meristem/drug effects/*physiology ; Morphogenesis/physiology ; Naphthaleneacetic Acids/pharmacology ; Plant Growth Regulators/pharmacology ; Plant Shoots/anatomy & histology/drug effects/physiology ; Purines ; *Regeneration ; Seeds/physiology ; *Tissue Culture Techniques ; }, abstract = {Rapid and genotype-independent protocols for two direct in vitro morphogenesis pathways including direct shoot organogenesis from embryo and direct shoot proliferation from node have been developed in cumin (Cuminum cyminum L.). Direct regenerations occurring without passing callus phase are important since fewer somaclonal variation and genotype-dependency are likely to arise from these methods in comparison with regenerations trough callus. After embryo culture, shoots with single-cellular origin were regenerated from the meristematic zone of embryo without any intermediate callus phase. In contrast, proliferated shoots with multi-cellular origin were directly regenerated from the axillary buds (meristems) of node explants. Effects of different concentrations of 6-Benzylaminopurine (BAP), alpha-Naphthaleneacetic Acid (NAA) and Indole-3-kcetic Acid (IAA) on B5 medium of embryo and node cultures as well as subculture were studied in detail. In direct organogenesis pathway from embryo explant, 0.1 mg L(-1) NAA + 1 mg L(-1) IAA resulted the highest shoot regeneration response (89.5 shoots per regenerated explant), whereas 0.1 mg L(-1) BAP + 1 mg L(-1) NAA was the most effective combination in direct shoot proliferation from node explant (42 shoots per regenerated explant). BAP (cytokinin) revealed the inhibitory effect on induction of direct shoot organogenesis pathway from embryo explant, while low concentration of BAP (0.1 mg L(-1)) had positive effect on direct shoot proliferation pathway from node explant. Subculturing was not necessary for shoot multiplication and elongation in embryo culture, whereas multiplication and elongation of shoots in node culture were associated to subculture on growth regulator-free medium. In other part of study, the behavior of different cumin genotypes in direct regeneration pathways was studied. Both direct organogenesis and direct proliferation pathways were applicable to different cumin genotypes and regenerated plants were phenotypically normal. This study supports the feasibility of combined direct regenerations protocols from embryo and node of cumin in germplasm conservation by in vitro cloning and genetic improvement programs.}, } @article {pmid17465887, year = {2007}, author = {Lee, CT and Risom, T and Strauss, WM}, title = {Evolutionary conservation of microRNA regulatory circuits: an examination of microRNA gene complexity and conserved microRNA-target interactions through metazoan phylogeny.}, journal = {DNA and cell biology}, volume = {26}, number = {4}, pages = {209-218}, doi = {10.1089/dna.2006.0545}, pmid = {17465887}, issn = {1044-5498}, mesh = {Animals ; Conserved Sequence ; *Evolution, Molecular ; Gene Dosage ; Gene Expression Regulation ; Humans ; MicroRNAs/*genetics ; Models, Genetic ; Phylogeny ; }, abstract = {During the last decade, a variety of critical biological processes, including early embryo development, cell proliferation, differentiation, apoptosis, and metabolic regularity, have been shown to be genetically regulated by a large gene family encoding a class of tiny RNA molecules termed microRNAs (miRNAs). All miRNAs share a common biosynthetic pathway and reaction mechanisms. The sequence of many miRNAs is found to be conserved, in their mature form, among different organisms. In addition, the evolutionary appearance of multicellular organisms appears to correlate with the appearance of the miRNA pathway for regulating gene expression. The miRNA pathway has the potential to regulate vast networks of gene products in a coordinate manner. Recent evidence has not only implicated the miRNA pathway in regulating a vast array of basic cellular processes but also specialized processes that are required for cellular identity and tissue specificity. A survey of the literature shows that some miRNA pathways are conserved virtually intact throughout phylogeny while miRNA diversity also correlates with speciation. The number of miRNA genes, the expression of miRNAs, and target diversities of miRNAs tend to be positively correlated with morphological complexities observed in animals. Thus, organismal complexity can be estimated by the complexity of the miRNA circuitry. The complexity of the miRNA gene families establishes a link between genotypic complexity and phenotypic complexity in animal evolution. In this paper, we start with the discussion of miRNA conservation. Then we interpret the trends in miRNA conservation to deduce miRNA evolutionary trends in metazoans. Based on these conservation patterns observed in each component of the miRNA regulatory system, we attempt to propose a global insight on the probable consistency between morphological evolution in animals and the molecular evolution of miRNA gene activity in the cell.}, } @article {pmid17463168, year = {2007}, author = {Hirabayashi, Y and Yoon, BI and Tsuboi, I and Huo, Y and Kodama, Y and Kanno, J and Ott, T and Trosko, JE and Inoue, T}, title = {Protective role of connexin 32 in steady-state hematopoiesis, regeneration state, and leukemogenesis.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {232}, number = {5}, pages = {700-712}, pmid = {17463168}, issn = {1535-3702}, mesh = {Animals ; Bone Marrow Cells/drug effects/metabolism/radiation effects ; Bone Marrow Transplantation ; Cell Proliferation/drug effects/radiation effects ; Connexins/genetics/metabolism/*physiology ; Female ; Flow Cytometry ; Fluorouracil/pharmacology ; Gene Expression Profiling ; Genotype ; Hematopoiesis/*physiology ; Hematopoietic Stem Cells/metabolism ; Immunohistochemistry ; Immunosuppressive Agents/pharmacology ; Leukemia/chemically induced/*physiopathology ; Male ; Methylnitrosourea/toxicity ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; RNA, Messenger/genetics/metabolism ; Regeneration/*physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Spleen/cytology/metabolism ; }, abstract = {The role of gap junctions formed by connexins (Cxs) has been implicated in the homeostatic regulation of multicellular systems. Primitive hematopoietic progenitor cells form a multicellular system, but a previous report states that Cx32 is not expressed in the bone marrow. Thus, a question arises as to why Cx molecules are not detected in the hematopoietic tissue other than in stromal cells. Based on our preliminary study, which suggested a potential impairment of hematopoiesis in Cx32-knockout (KO) mice, the objectives of the present study were to determine whether Cx32 functions in the bone marrow during steady-state hematopoiesis and to examine its possible protective roles during regeneration after chemical abrasions and during leukemogenesis after the administration of a secondary genotoxic chemical, methyl nitrosourea (MNU). As a result, the Cx32 molecule, functioning in the hematopoietic stem cell (HSC) compartment during steady-state hematopoiesis, was observed for the first time; the expressions of Cx32 at the mRNA level, as determined by polymerase chain reaction analysis, and at the protein level, determined using an anti-Cx32 antibody, were observed only in the lin(-)c-kit(+) HSC fraction, using a combination of immunobead-density gradient and immunomagnetic bead separation. Hematopoiesis was impaired in the absence of Cx32, and it was delayed during regeneration after chemical abrasion with 5-fluorouracil at 150 mg/kg body wt in Cx32-KO mice. Cx32-KO mice showed increased leukemogenicity compared with wild-type mice after MNU injection; furthermore, in a competitive assay for leukemogenicity in mice that had been lethally irradiated and repopulated with a mixed population of bone marrow cells from Cx32-KO mice and wild-type mice, the resulting leukemias originated predominantly from Cx32-KO bone marrow cells. In summary, the role of Cx32 in hematopoiesis was not previously recognized, and Cx32 was expressed only in HSCs and their progenitor cells. The results indicate that Cx32 in wild-type mice protects HSCs from chemical abrasion and leukemogenic impacts.}, } @article {pmid17462635, year = {2007}, author = {Krämer, U and Talke, IN and Hanikenne, M}, title = {Transition metal transport.}, journal = {FEBS letters}, volume = {581}, number = {12}, pages = {2263-2272}, doi = {10.1016/j.febslet.2007.04.010}, pmid = {17462635}, issn = {0014-5793}, mesh = {Biological Evolution ; Biological Transport, Active ; Cation Transport Proteins/genetics/metabolism ; Cell Membrane/metabolism ; Chelating Agents/metabolism ; Chloroplast Proton-Translocating ATPases/genetics/metabolism ; Genes, Plant ; Homeostasis ; Iron/metabolism ; Membrane Transport Proteins/chemistry/genetics/metabolism ; Models, Biological ; Multigene Family ; Plant Proteins/chemistry/genetics/metabolism ; Plants/genetics/*metabolism ; Protein Structure, Tertiary ; Transition Elements/*metabolism ; }, abstract = {Transition metal transporters are of central importance in the plant metal homeostasis network which maintains internal metal concentrations within physiological limits. An overview is given of the functions of known transition metal transporters in the context of the unique chemical properties of their substrates. The modifications of the metal homeostasis network associated with the adaptation to an extreme metalliferous environment are illustrated in two Brassicaceae metal hyperaccumulator model plants based on cross-species transcriptomics studies. In a comparison between higher plants and unicellular algae, hypotheses are generated for evolutionary changes in metal transporter complements associated with the transition to multicellularity.}, } @article {pmid17449818, year = {2007}, author = {Mattick, JS}, title = {A new paradigm for developmental biology.}, journal = {The Journal of experimental biology}, volume = {210}, number = {Pt 9}, pages = {1526-1547}, doi = {10.1242/jeb.005017}, pmid = {17449818}, issn = {0022-0949}, mesh = {Alternative Splicing/genetics ; Developmental Biology/*methods/*trends ; Embryonic Development/*genetics ; Epigenesis, Genetic/*genetics ; *Evolution, Molecular ; Gene Expression Regulation/*genetics ; Gene Regulatory Networks/genetics ; Genome/*genetics ; RNA, Messenger/genetics ; Regulatory Sequences, Ribonucleic Acid/*genetics ; Systems Biology/*trends ; }, abstract = {It is usually thought that the development of complex organisms is controlled by protein regulatory factors and morphogenetic signals exchanged between cells and differentiating tissues during ontogeny. However, it is now evident that the majority of all animal genomes is transcribed, apparently in a developmentally regulated manner, suggesting that these genomes largely encode RNA machines and that there may be a vast hidden layer of RNA regulatory transactions in the background. I propose that the epigenetic trajectories of differentiation and development are primarily programmed by feed-forward RNA regulatory networks and that most of the information required for multicellular development is embedded in these networks, with cell-cell signalling required to provide important positional information and to correct stochastic errors in the endogenous RNA-directed program.}, } @article {pmid17448980, year = {2007}, author = {Bowman, JL and Floyd, SK and Sakakibara, K}, title = {Green genes-comparative genomics of the green branch of life.}, journal = {Cell}, volume = {129}, number = {2}, pages = {229-234}, doi = {10.1016/j.cell.2007.04.004}, pmid = {17448980}, issn = {0092-8674}, mesh = {*Biological Evolution ; Genome, Plant ; *Genomics ; Photosynthesis ; Phylogeny ; Plants/anatomy & histology/*genetics/metabolism ; }, abstract = {As more plant genome sequences become available, researchers are increasingly using comparative genomics to address some of the major questions in plant biology. Such questions include the evolution of photosynthesis and multicellularity, the developmental genetic changes responsible for alterations in body plan, and the origin of important plant innovations such as roots, leaves, and vascular tissue.}, } @article {pmid17442504, year = {2007}, author = {Chen, CC and Li, WH and Sung, HM}, title = {Patterns of internal gene duplication in the course of metazoan evolution.}, journal = {Gene}, volume = {396}, number = {1}, pages = {59-65}, doi = {10.1016/j.gene.2007.02.021}, pmid = {17442504}, issn = {0378-1119}, support = {GM 30998/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans ; Carrier Proteins/chemistry ; Drosophila melanogaster ; Eukaryotic Cells/*metabolism ; *Evolution, Molecular ; *Gene Duplication ; Genome ; Humans ; Protein Structure, Tertiary ; Repetitive Sequences, Amino Acid ; Software ; Transcription Factors/chemistry ; }, abstract = {Internal duplication can enhance the function of a gene or provide raw material for the emergence of a new function in a gene. Therefore, it is interesting to see whether the frequency of internal duplication has increased during metazoan evolution. The growing number of sequenced eukaryotic genomes provides an excellent opportunity to study the change in the pattern of internal duplication in the course of metazoan evolution. We studied repeated segments in proteins in the proteomes of 11 eukaryotes. We found that the frequency of internal duplication in Caenorhabditis elegans and Drosophila melanogaster (two protostomes) is higher than that in fungi but lower than that in chordates. Moreover, the frequencies of internal duplication for the chordates studied are largely similar. We classified orthologous proteins of chordates into three antiquity groups and found that more recently derived proteins in the metazoan lineage have higher repetitiveness than older ones. Our analysis suggests that lineage-specific internal duplication in protein evolution increases with organismal complexity before the emergence of chordates but not so afterward. Proteins with repeated regions might have been preferred before the protostome-chordate split. This finding supports the suggestion that exon-shuffling occurred more frequently after the first multicellular organism appeared and might have contributed to the metazoan radiation.}, } @article {pmid17439618, year = {2007}, author = {Galley, C and Linder, HP}, title = {The phylogeny of the Pentaschistis clade (Danthonioideae, Poaceae) based on chloroplast DNA, and the evolution and loss of complex characters.}, journal = {Evolution; international journal of organic evolution}, volume = {61}, number = {4}, pages = {864-884}, doi = {10.1111/j.1558-5646.2007.00067.x}, pmid = {17439618}, issn = {0014-3820}, mesh = {Base Sequence ; Bayes Theorem ; DNA, Chloroplast/*genetics ; Exocrine Glands/*anatomy & histology ; Models, Genetic ; Molecular Sequence Data ; *Phylogeny ; Plant Leaves/*anatomy & histology ; Poaceae/anatomy & histology/classification/*genetics ; Sequence Analysis, DNA ; Soil/analysis ; }, abstract = {We construct a species-level phylogeny for the Pentaschistis clade based on chloroplast DNA, from the following regions: trnL-F, trnT-L, atpB-rbcL, rpL16, and trnD-psbA. The clade comprises 82 species in three genera, Pentaschistis, Pentameris, and Prionanthium. We demonstrate that Prionanthium is nested in Pentaschistis and that this clade is sister to a clade of Pentameris plus Pentaschistis tysonii. Forty-three of the species in the Pentaschistis clade have multicellular glands and we use ancestral character state reconstruction to show that they have been gained twice or possibly once, and lost several times. We suggest that the maintenance, absence, loss, and gain of glands are correlated with leaf anatomy type, and additionally that there is a difference in the degree of diversification of lineages that have these different character combinations. We propose that both glands and sclerophyllous leaves act as defense systems against herbivory, and build a cost/benefit model in which multicellular glands or sclerophyllous leaves are lost when the alternative defense system evolves. We also investigate the association between leaf anatomy type and soil nutrient type on which species grow. There is little phylogenetic constraint in soil nutrient type on members of the Pentaschistis clade, with numerous transitions between oligotrophic and eutrophic soils. However, only orthophyllous-leaved species diversify on eutrophic soils. We suggest that the presence of these glands enables the persistence of orthophyllous lineages and therefore diversification of the Pentaschistis clade on eutrophic as well as oligotrophic soils.}, } @article {pmid17434518, year = {2007}, author = {Morris, DJ and Adams, A}, title = {Sacculogenesis of Buddenbrockia plumatellae (Myxozoa) within the invertebrate host Plumatella repens (Bryozoa) with comments on the evolutionary relationships of the Myxozoa.}, journal = {International journal for parasitology}, volume = {37}, number = {10}, pages = {1163-1171}, doi = {10.1016/j.ijpara.2007.03.001}, pmid = {17434518}, issn = {0020-7519}, support = {BB/C505024/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Bryozoa/cytology/*parasitology/*physiology ; Host-Parasite Interactions ; }, abstract = {Members of the phylum Myxozoa are obligate parasites, primarily of aquatic organisms. Their phylogeny has remained problematic, with studies placing them within either the Bilateria or Cnidaria. The discovery that the enigmatic Buddenbrockia plumatellae is a myxozoan that possesses distinct bilaterian features appeared to have finally resolved the debate. B. plumatellae is described as a triploblastic 'worm-like' organism, within which typical myxozoan malacospores form. Using EM we examined the early development of the B. plumatellae 'worms' within the bryozoan host Plumatella repens. The initial development involved numerous unicellular, amoeboid pre-saccular stages that were present within the basal lamina of the host's body wall. These stages migrate immediately beneath the peritoneum where a significant host tissue reaction occurs. The stages aggregate, initiating the formation of a 'worm'. The base of a developing 'worm' forms a pseudosyncytium which resolves into an ectoderm surrounding a mesendoderm. The pseudosyncytium is directly anchored into neighbouring host cells via masses of striated fibres. The replication of the ectodermal and mesendodermal cells extends the developing 'worm' into the coelom of the host. The mesendoderm resolves to form a mesoderm and an endoderm. Myogenesis appears to be initiated from the anchored end of the 'worm' and develops along the mesoderm. The aggregation and differentiation of amoeboid pre-saccular stages to initiate the 'worm' draws analogies to the sacculogenesis observed for Tetracapsuloides bryosalmonae, B. plumatellae's sister taxon within the class Malacosporea. The development of a multicellular, spore forming organism, from single cells does not correlate to any bilaterian or cnidarian species. Current phylogenies indicate the Myxozoa are basal bilaterians along with the Acoela and Mesozoa. Comparison with these other basal groups may help to resolve the placement of Myxozoa within the tree of life.}, } @article {pmid17418905, year = {2007}, author = {Brunet, I and Di Nardo, AA and Sonnier, L and Beurdeley, M and Prochiantz, A}, title = {The topological role of homeoproteins in the developing central nervous system.}, journal = {Trends in neurosciences}, volume = {30}, number = {6}, pages = {260-267}, doi = {10.1016/j.tins.2007.03.010}, pmid = {17418905}, issn = {0166-2236}, mesh = {Animals ; Axons/metabolism ; Central Nervous System/cytology/*growth & development/metabolism ; Homeodomain Proteins/*metabolism ; Humans ; Morphogenesis/*physiology ; Neurons/cytology/metabolism ; Transcription Factors/*metabolism ; }, abstract = {Homeogenes encode homeoprotein transcription factors that have fundamental roles in development. They are key players in genetic networks that lay out the body plan and also determine morphology and physiology at the cellular and multicellular level. However, homeoproteins share activities that extend beyond transcription, including translation regulation and signalling. For example, homeoproteins participate in the definition of territories in the neuroepithelium and also have a function in axonal guidance. Based on these examples, we propose that homeoproteins are not only morphogenetic transcription factors, but also morphogens themselves.}, } @article {pmid17416994, year = {2007}, author = {Adams, JC and Engel, J}, title = {Bioinformatic analysis of adhesion proteins.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {370}, number = {}, pages = {147-172}, doi = {10.1007/978-1-59745-353-0_12}, pmid = {17416994}, issn = {1064-3745}, mesh = {Animals ; Cadherins/genetics/metabolism ; Cell Adhesion ; Cell Adhesion Molecules/genetics/*metabolism ; Computational Biology/*methods ; Extracellular Matrix/metabolism ; Genomics/methods ; Humans ; Integrins/genetics/metabolism ; Phylogeny ; }, abstract = {Proteins that mediate cell-cell and cell-extracellular matrix (ECM) adhesion have been fundamental in the evolution of multicellular animals. Fibrillar collagens, proteoglycans, integrins, and cadherins are present in all animals from sponges to mammals, and many other adhesion proteins have arisen during animal evolution. In general, adhesion proteins are large multidomain molecules and are encoded in larger gene families in vertebrates than in invertebrates. With the increasing availability of completely sequenced genomes representing different points on the animal tree of life, bioinformatics is proving to be a very valuable approach for the analysis of the domain organization and relationships of adhesion proteins, which can direct or enhance experimental tests. Here we describe, with examples from the literature, the major methods for identifying sequence homologies; analyzing domain organization and potential for oligomerization; analyzing sequence relationships by multiple sequence alignments and phylogenetic trees, and assessing adhesion proteins as components of functional pathways and tissue systems through comparative genomics.}, } @article {pmid17406890, year = {2007}, author = {Kurczyńska, EU and Gaj, MD and Ujczak, A and Mazur, E}, title = {Histological analysis of direct somatic embryogenesis in Arabidopsis thaliana (L.) Heynh.}, journal = {Planta}, volume = {226}, number = {3}, pages = {619-628}, pmid = {17406890}, issn = {0032-0935}, mesh = {Arabidopsis/*cytology/*embryology ; Arabidopsis Proteins/genetics ; Cell Communication ; Cell Division ; Cell Wall/metabolism ; *Embryonic Development ; Glucuronidase/metabolism ; Indoleacetic Acids/metabolism ; Promoter Regions, Genetic/genetics ; Seeds/cytology/embryology ; Transcription Factors/genetics ; }, abstract = {In Arabidopsis the in vitro culture of immature zygotic embryos (IZEs) at a late stage of development, on the solid medium containing synthetic auxin, leads to formation of somatic embryos via direct somatic embryogenesis (DSE). The presented results provide evidence that in IZE cells competent for DSE are located in the protodermis and subprotodermis of the adaxial side of cotyledons and somatic embryos displayed a single- or multicellular origin. Transgenic Arabidopsis lines expressing the GUS reporter gene, driven by the DR5 and LEC2 promoters, were used to analyse the distribution of auxin to mark embryogenic cells in cultured explants and develop somatic embryos. The analysis showed that at the start of the culture auxin was accumulated in all explant tissues, but from the fourth day onwards its location shifted to the protodermis and subprotodermis of the explant cotyledons. In globular somatic embryos auxin was detected in all cells, with a higher concentration in the protodermis, and in the heart stage its activity was mainly displayed in the shoot, root pole and cotyledon primordia. The embryogenic nature of dividing protodermal and subprotodermal cells accumulating auxin was confirmed by high expression of promoter activity of LEC2 in these cells. Analysis of symplasmic tracer (CFDA) distribution indicated symplasmic isolation between tissues engaged in DSE and other parts of an explant. Symplasmic isolation of somatic embryos from the explant was also detected.}, } @article {pmid17400358, year = {2007}, author = {Bedard, K and Lardy, B and Krause, KH}, title = {NOX family NADPH oxidases: not just in mammals.}, journal = {Biochimie}, volume = {89}, number = {9}, pages = {1107-1112}, doi = {10.1016/j.biochi.2007.01.012}, pmid = {17400358}, issn = {0300-9084}, mesh = {Animals ; Evolution, Molecular ; Fungi/enzymology/genetics ; Mammals/genetics/*metabolism ; Models, Biological ; NADPH Oxidases/genetics/*metabolism ; Phylogeny ; Plants/enzymology/genetics ; Reactive Oxygen Species/metabolism ; }, abstract = {NOX family NADPH oxidases are enzymes whose biological function is electron transport and the generation of reactive oxygen species (ROS). NOX enzymes in mammalian organisms have received most attention. However, NOX enzymes are widely distributed in different kingdoms of life. While they are not found in prokaryotes and most unicellular eukaryotes, they are present in fungi, plants, and animals. The identity of the ancestral NOX is not known, but most likely it: (i) possessed the basic NOX structure consisting of 6 transmembrane domains (containing two assymmetrical hemes) and a long cytoplasmic C-terminal (containing the FAD and NADPH binding sites); and (ii) emerged before the divergence of life into fungi, plants, and animals. During evolution, acquisition of a Ca(2+)-binding EF hand domain by an ancestral NOX, led to NOX5-like isoforms. DUOX isoforms presumably developed from a NOX5-like isoform through the additional acquisition of a peroxidase homology domain. The expression pattern of NOX enzymes is specific to each kingdom of life. Fungi express only ancestral-type isoforms, and plants only NOX5-like isoforms. NOX expression patterns in animals are complex and ancestral NOXes, NOX5-like isoforms and DUOXes are generally found. But there are exceptions; for example rodents lack NOX5 and Caenorhabditis elegans expresses only DUOXes. Biological functions of NOX enzymes include, among others, host defense, post-translational modification of proteins, and regulation cell growth and differentiation. In summary, the invention of NOX enzymes early in the development of life was a success story: there is no evidence of multicellular life without NOX enzymes.}, } @article {pmid17390287, year = {2007}, author = {Doolen, JF and Geddes, GC and Blackstone, NW}, title = {Multicellular redox regulation in an early-evolving animal treated with glutathione.}, journal = {Physiological and biochemical zoology : PBZ}, volume = {80}, number = {3}, pages = {317-325}, doi = {10.1086/512587}, pmid = {17390287}, issn = {1522-2152}, mesh = {Animals ; Biological Evolution ; Glutathione/*pharmacology ; Oxidation-Reduction/drug effects ; Reactive Oxygen Species/metabolism ; Scyphozoa/*drug effects/*physiology ; }, abstract = {Redox signaling has emerged as a unifying theme in many seemingly disparate disciplines. Such signaling has been widely studied in bacteria and eukaryotic organelles and is often mediated by reactive oxygen species (ROS). In this context, reduced glutathione (GSH) acts as an important intracellular antioxidant, diminishing ROS and potentially affecting redox signaling. Complementing this cell-level perspective, colonial hydroids can be a useful model for understanding organism-level redox signaling. These simple, early-evolving animals consist of feeding polyps connected by tubelike stolons. Colonies treated exogenously with GSH or reduced glutathione ethyl ester (GEE) were expected to show a morphological change to sheetlike growth typical of low levels of ROS. Contrary to expectations, diminished stolon branching and polyp initiation was observed. Such runnerlike growth is associated with higher levels of ROS, and surprisingly, such higher levels were found in GSH- and GEE-treated colonies. Further investigations show that GSH triggered a feeding response in hydroid polyps, increasing oxygen uptake but at the same time relaxing mitochondrion-rich contractile regions at the base of polyps. Diminished gastrovascular flow and increased emissions of mitochondrial ROS also correlated with the observed runnerlike growth. In contrast to cell-level, "bottom-up" views of redox signaling, here the phenotype may arise from a "top-down" interaction of mitochondrion-rich regions and organism-level physiology. Such multicellular redox regulation may commonly occur in other animals as well.}, } @article {pmid17369437, year = {2007}, author = {Sanderfoot, A}, title = {Increases in the number of SNARE genes parallels the rise of multicellularity among the green plants.}, journal = {Plant physiology}, volume = {144}, number = {1}, pages = {6-17}, pmid = {17369437}, issn = {0032-0889}, mesh = {Cluster Analysis ; *Evolution, Molecular ; Expressed Sequence Tags ; Gene Duplication ; *Genome, Plant ; Multigene Family ; Phylogeny ; Plant Cells ; Plants/*genetics ; SNARE Proteins/chemistry/*genetics/physiology ; Vacuoles/genetics ; }, abstract = {The green plant lineage is the second major multicellular expansion among the eukaryotes, arising from unicellular ancestors to produce the incredible diversity of morphologies and habitats observed today. In the unicellular ancestors, secretion of material through the endomembrane system was the major mechanism for interacting and shaping the external environment. In a multicellular organism, the external environment can be made of other cells, some of which may have vastly different developmental fates, or be part of different tissues or organs. In this context, a given cell must find ways to organize its secretory pathway at a level beyond that of the unicellular ancestor. Recently, sequence information from many green plants have become available, allowing an examination of the genomes for the machinery involved in the secretory pathway. In this work, the SNARE proteins of several green plants have been identified. While little increase in gene number was seen in the SNAREs of the early secretory system, many new SNARE genes and gene families have appeared in the multicellular green plants with respect to the unicellular plants, suggesting that this increase in the number of SNARE genes may have some relation to the rise of multicellularity in green plants.}, } @article {pmid17368752, year = {2007}, author = {Halabe Bucay, A}, title = {The biological significance of cancer: mitochondria as a cause of cancer and the inhibition of glycolysis with citrate as a cancer treatment.}, journal = {Medical hypotheses}, volume = {69}, number = {4}, pages = {826-828}, doi = {10.1016/j.mehy.2007.02.002}, pmid = {17368752}, issn = {0306-9877}, mesh = {Antineoplastic Agents/therapeutic use ; Cell Transformation, Neoplastic ; Citrates/*therapeutic use ; Glycolysis/drug effects/*physiology ; Humans ; Mitochondria/drug effects/*physiology ; Models, Biological ; Neoplasms/drug therapy/*physiopathology ; }, abstract = {In this article, I present the hypothesis that cancer presents due to the domination of the cell by mitochondria, which, from an evolution viewpoint, appeared in multi-cellular living being with the incorporation of a bacteria into a primitive cell, the bacteria sustained itself as mitochondria and these conserved their identity and bacterial characteristics, based on this, the hypothesis is suggested of the biological competition between the cell and the mitochondria; the mitochondria, on establishing itself as an independent entity within the cell, created the need to permanently remain in the cytoplasm of the cell, thus, from an energy viewpoint, when a cell becomes malignant, the mitochondria are the sole beneficiaries, as there is an ideal environment at the cellular level for the mitochondria to sustain their functions, and from this hypothesis, the treatment for fighting cancer consists of inhibiting glycolysis, being the principal source of energy for the mitochondria, this is achieved by administering citrate to cancer patients, as the citrate inhibits the phosphofructokinase enzyme, the pyruvate dehydrogenase complex and the succinate dehydrogenase enzyme of Krebs cycle, thus, the mitochondria will be forced to limit their metabolism and, secondarily, will lower the reproduction capacity of the cell in general.}, } @article {pmid17367545, year = {2007}, author = {Eisenhaber, B and Chumak, N and Eisenhaber, F and Hauser, MT}, title = {The ring between ring fingers (RBR) protein family.}, journal = {Genome biology}, volume = {8}, number = {3}, pages = {209}, pmid = {17367545}, issn = {1474-760X}, support = {P 17888/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Amino Acid Motifs ; Evolution, Molecular ; Gene Expression Regulation ; *Proteins/chemistry/genetics/metabolism/physiology ; Tissue Distribution ; *Zinc Fingers ; }, abstract = {Proteins of the ring between ring fingers (RBR)-domain family are characterized by three groups of specifically clustered (typically eight) cysteine and histidine residues. Whereas the amino-terminal ring domain (N-RING) binds two zinc ions and folds into a classical cross-brace ring finger, the carboxy-terminal ring domain (C-RING) involves only one zinc ion. The three-dimensional structure of the central ring domain, the IBR domain, is still unsolved. About 400 genes coding for RBR proteins have been identified in the genomes of uni- and multicellular eukaryotes and some of their viruses, but the family has not been found in archaea or bacteria. The RBR proteins are classified into 15 major subfamilies (besides some orphan cases) by the phylogenetic relationships of the RBR segments and the conservation of their sequence architecture. The RBR domain mediates protein-protein interactions and a subset of RBR proteins has been shown to function as E3 ubiquitin ligases. RBR proteins have attracted interest because of their involvement in diseases such as parkinsonism, dementia with Lewy bodies, and Alzheimer's disease, and in susceptibility to some intracellular bacterial pathogens. Here, we present an overview of the RBR-domain containing proteins and their subcellular localization, additional domains, function, specificity, and regulation.}, } @article {pmid17360592, year = {2007}, author = {Popescu, SC and Popescu, GV and Bachan, S and Zhang, Z and Seay, M and Gerstein, M and Snyder, M and Dinesh-Kumar, SP}, title = {Differential binding of calmodulin-related proteins to their targets revealed through high-density Arabidopsis protein microarrays.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {104}, number = {11}, pages = {4730-4735}, pmid = {17360592}, issn = {0027-8424}, mesh = {Arabidopsis/genetics/*metabolism ; Calmodulin/*chemistry/metabolism ; Computational Biology ; *Genes, Plant ; Models, Genetic ; Open Reading Frames ; Phylogeny ; Plant Proteins ; Protein Array Analysis ; Protein Binding ; Protein Interaction Mapping ; Proteins/chemistry ; Proteomics/methods ; Recombinant Proteins/chemistry ; }, abstract = {Calmodulins (CaMs) are the most ubiquitous calcium sensors in eukaryotes. A number of CaM-binding proteins have been identified through classical methods, and many proteins have been predicted to bind CaMs based on their structural homology with known targets. However, multicellular organisms typically contain many CaM-like (CML) proteins, and a global identification of their targets and specificity of interaction is lacking. In an effort to develop a platform for large-scale analysis of proteins in plants we have developed a protein microarray and used it to study the global analysis of CaM/CML interactions. An Arabidopsis thaliana expression collection containing 1,133 ORFs was generated and used to produce proteins with an optimized medium-throughput plant-based expression system. Protein microarrays were prepared and screened with several CaMs/CMLs. A large number of previously known and novel CaM/CML targets were identified, including transcription factors, receptor and intracellular protein kinases, F-box proteins, RNA-binding proteins, and proteins of unknown function. Multiple CaM/CML proteins bound many binding partners, but the majority of targets were specific to one or a few CaMs/CMLs indicating that different CaM family members function through different targets. Based on our analyses, the emergent CaM/CML interactome is more extensive than previously predicted. Our results suggest that calcium functions through distinct CaM/CML proteins to regulate a wide range of targets and cellular activities.}, } @article {pmid17334709, year = {2007}, author = {Cetkovic, H and Mikoc, A and Müller, WE and Gamulin, V}, title = {Ras-like small GTPases form a large family of proteins in the marine sponge Suberites domuncula.}, journal = {Journal of molecular evolution}, volume = {64}, number = {3}, pages = {332-341}, pmid = {17334709}, issn = {0022-2844}, mesh = {Amino Acid Sequence ; Animals ; DNA, Complementary/genetics ; Databases, Nucleic Acid ; *Evolution, Molecular ; Expressed Sequence Tags ; Humans ; Molecular Sequence Data ; Monomeric GTP-Binding Proteins/chemistry/*genetics ; Phylogeny ; Sequence Alignment ; Suberites/enzymology/*genetics ; }, abstract = {Sponges (Porifera) are the simplest and the most ancient metazoan animals, which branched off first from the common ancestor of all multicellular animals. We have inspected approximately 13,000 partial cDNA sequences (ESTs) from the marine sponge Suberites domuncula and have identified full or partial cDNA sequences coding for approximately 50 different Ras-like small GTPases. Forty-four sponge proteins from the Ras family are described here: 6 proteins from the Ras subfamily, 5 from Rho, 6 from Arf, 1 Ran, and 26 Rabs or Rab-like proteins. No isoforms of these proteins were detected; the closest related proteins are two Rho proteins with 74% identity. Small GTPases from sponge display a higher degree of sequence conservation with orthologues from vertebrates (53%-93% identity) than with those from either Caenorhabditis elegans or Drosophila melanogaster. The real number of small GTPases in this sponge is certainly much higher than 50, because the actual S. domuncula database of approximately 13,000 ESTs contains at most 3000 nonredundant cDNA sequences. The number of genes for Ras-like small GTPases in yeast, C. elegans, D. melanogaster, and humans is 30, 56, 90, and 174, respectively. Both model invertebrates have only 29 Rabs or Rab-like proteins, compared with 26 already found in sponge, and are missing at least 1 Rab (Rab24) present in S. domuncula and mammals. Our results indicate that duplications and diversifications of genes encoding Ras-like small GTPases, especially the Rab subfamily of small GTPases, happened very early in the evolution of Metazoa.}, } @article {pmid17331578, year = {2007}, author = {Stavitsky, AB}, title = {The innate immune response to infection, toxins and trauma evolved into networks of interactive, defensive, reparative, regulatory, injurious and pathogenic pathways.}, journal = {Molecular immunology}, volume = {44}, number = {11}, pages = {2787-2799}, doi = {10.1016/j.molimm.2007.01.011}, pmid = {17331578}, issn = {0161-5890}, mesh = {Animals ; Cytokines/immunology ; Female ; Humans ; *Immunity, Innate ; Infections/*immunology ; Inflammation/immunology ; Male ; Signal Transduction/immunology ; Toxins, Biological/*immunology/toxicity ; Wound Healing/*immunology ; }, abstract = {It is hypothesized that, under selective pressure from infections, trauma and toxins, multicellular organisms evolved an innate immune response (IIR): (1) comprising neural, endocrine, biochemical and cellular pathways that restore homeostasis through pathogen clearance, repair of injury and regulation of inflammation, but also mediate injury and disease; (2) that functions independently of as well as in concert with the adaptive immune response (AIR); (3) whose functions in health and disease depend upon cross-talk and networking among these pathways. A critical review of the literature provides strong evidence to support the evolution of the IIR, Propositions 1 and 2 and partial support for Proposition 3: there are numerous interactions among the mammalian IIR pathways, but there is no direct evidence for more complex functioning networks in vivo. Some implications and questions raised by the hypothesis are presented.}, } @article {pmid17321123, year = {2007}, author = {Nobukuni, T and Kozma, SC and Thomas, G}, title = {hvps34, an ancient player, enters a growing game: mTOR Complex1/S6K1 signaling.}, journal = {Current opinion in cell biology}, volume = {19}, number = {2}, pages = {135-141}, doi = {10.1016/j.ceb.2007.02.019}, pmid = {17321123}, issn = {0955-0674}, support = {R01 CA-120475-01/CA/NCI NIH HHS/United States ; R01 DK-73802-01/DK/NIDDK NIH HHS/United States ; U01 CA84292-06/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Autophagy ; Endosomes/metabolism ; Humans ; Models, Biological ; Phosphatidylinositol 3-Kinases/*metabolism ; Protein Kinases/*metabolism ; Ribosomal Protein S6 Kinases, 70-kDa/*metabolism ; *Signal Transduction ; TOR Serine-Threonine Kinases ; }, abstract = {Recent studies have shown that the nutrient input to the mTOR Complex1/S6K1 signaling pathway is mediated by class 3 PI3K or hVps34, the oldest member of the PI3K family. Moreover, studies to date would suggest that during the evolution of multicellular organisms this ancient branch of the pathway was merged with the growth-factor-hormone-controlled class 1 PI3K pathway at the level of mTOR Complex1 to control the development and growth of the organism. However, hVps34 also plays a role in the regulation of macroautophagy - the mechanism by which cells generate nutrients, such as amino acids, through the degradation of intracellular complexes, including mitochondria and ribosomes. These functions of hVps34 initially appear contradictory, since increased mTOR Complex1 activation is triggered by increased amino acid levels, while autophagy is triggered when cells are faced with amino acid deprivation.}, } @article {pmid17313526, year = {2007}, author = {Kooijman, SA and Troost, TA}, title = {Quantitative steps in the evolution of metabolic organisation as specified by the Dynamic Energy Budget theory.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {82}, number = {1}, pages = {113-142}, doi = {10.1111/j.1469-185X.2006.00006.x}, pmid = {17313526}, issn = {1464-7931}, mesh = {Animals ; *Biological Evolution ; Biomass ; Body Temperature Regulation ; *Cell Physiological Phenomena ; Energy Metabolism/*physiology ; Homeostasis/physiology ; Humans ; Kinetics ; *Models, Biological ; Thermodynamics ; }, abstract = {The Dynamic Energy Budget (DEB) theory quantifies the metabolic organisation of organisms on the basis of mechanistically inspired assumptions. We here sketch a scenario for how its various modules, such as maintenance, storage dynamics, development, differentiation and life stages could have evolved since the beginning of life. We argue that the combination of homeostasis and maintenance induced the development of reserves and that subsequent increases in the maintenance costs came with increases of the reserve capacity. Life evolved from a multiple reserves - single structure system (prokaryotes, many protoctists) to systems with multiple reserves and two structures (plants) or single reserve and single structure (animals). This had profound consequences for the possible effects of temperature on rates. We present an alternative explanation for what became known as the down-regulation of maintenance at high growth rates in microorganisms; the density of the limiting reserve increases with the growth rate, and reserves do not require maintenance while structure-specific maintenance costs are independent of the growth rate. This is also the mechanism behind the variation of the respiration rate with body size among species. The DEB theory specifies reserve dynamics on the basis of the requirements of weak homeostasis and partitionability. We here present a new and simple mechanism for this dynamics which accounts for the rejection of mobilised reserve by busy maintenance/growth machinery. This module, like quite a few other modules of DEB theory, uses the theory of Synthesising Units; we review recent progress in this field. The plasticity of membranes that evolved in early eukaryotes is a major step forward in metabolic evolution; we discuss quantitative aspects of the efficiency of phagocytosis relative to the excretion of digestive enzymes to illustrate its importance. Some processes of adaptation and gene expression can be understood in terms of allocation linked to the relative workload of metabolic modules in (unicellular) prokaryotes and organs in (multicellular) eukaryotes. We argue that the evolution of demand systems can only be understood in the light of that of supply systems. We illustrate some important points with data from the literature.}, } @article {pmid17305841, year = {2007}, author = {Simões, P and Rose, MR and Duarte, A and Gonçalves, R and Matos, M}, title = {Evolutionary domestication in Drosophila subobscura.}, journal = {Journal of evolutionary biology}, volume = {20}, number = {2}, pages = {758-766}, doi = {10.1111/j.1420-9101.2006.01244.x}, pmid = {17305841}, issn = {1010-061X}, mesh = {Adaptation, Biological ; Animals ; *Breeding ; Drosophila/classification/genetics/*physiology ; *Evolution, Molecular ; Fertility ; Linear Models ; }, abstract = {The domestication of plants and animals is historically one of the most important topics in evolutionary biology. The evolutionary genetic changes arising from human cultivation are complex because of the effects of such varied processes as continuing natural selection, artificial selection, deliberate inbreeding, genetic drift and hybridization of different lineages. Despite the interest of domestication as an evolutionary process, few studies of multicellular sexual species have approached this topic using well-replicated experiments. Here we present a comprehensive study in which replicated evolutionary trajectories from several Drosophila subobscura populations provide a detailed view of the evolutionary dynamics of domestication in an outbreeding animal species. Our results show a clear evolutionary response in fecundity traits, but no clear pattern for adult starvation resistance and juvenile traits such as development time and viability. These results supply new perspectives on the confounding of adaptation with other evolutionary mechanisms in the process of domestication.}, } @article {pmid17302146, year = {2006}, author = {Jin, Y and Guo, PF and Sun, LM and Yu, XJ and Zhang, W}, title = {[Phylogenetic diversity of endocellular bacteria marine sponge Hymeniacidon perleve].}, journal = {Wei sheng wu xue bao = Acta microbiologica Sinica}, volume = {46}, number = {6}, pages = {875-878}, pmid = {17302146}, issn = {0001-6209}, mesh = {Alphaproteobacteria/classification ; Animals ; Bacteria/*classification/genetics ; Gammaproteobacteria/classification ; Phylogeny ; Polymorphism, Restriction Fragment Length ; Porifera/*microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Marine sponges are hosts of diverse bacteria that live in both intracellular and intercellular spaces of the multicellular animals. The aim of this study is to investigate the bacteria diversity inside the marine sponge cells of Hymeniacidon perleve by 16S rDNA gene sequences. To obtain pure sponge cells, a protocol has been developed in which the sponge tissues were firstly dissociated in CMFSW and cleaned several times. The purified sponge cells were subject to extraction of endocelluar bacterial DNA. The endocellular bacterial phylogenetic diversity of the marine sponge was determined by RFLP-16S rDNA sequencing of cloned DNA fragments. Thirteen of isolated 16S rDNA gene sequences were attributed to be alpha-Proteobacteria (5), gamma- Proteobacteria (5) and Planctomycetes (3). When compared to the bacterial diversity of the sponge tissues, alpha- and beta-proteobacteria are still the dominant bacteria genes, however Planctomycetes was not obtained in the sponge tissuse. These results indicated a different bacterial diversity in the sponge cells and sponge tissues.}, } @article {pmid17299594, year = {2007}, author = {Janhunen, P and Kaartokallio, H and Oksanen, I and Lehto, K and Lehto, H}, title = {Biological feedbacks as cause and demise of the Neoproterozoic icehouse: astrobiological prospects for faster evolution and importance of cold conditions.}, journal = {PloS one}, volume = {2}, number = {2}, pages = {e214}, pmid = {17299594}, issn = {1932-6203}, mesh = {Biodiversity ; Carbon Dioxide/chemistry/metabolism ; Carbon Isotopes/*analysis ; *Cold Climate ; *Earth, Planet ; Eukaryota/growth & development/metabolism/*physiology ; *Evolution, Planetary ; Exobiology ; *Feedback, Physiological ; Greenhouse Effect ; *Ice Cover ; Marine Biology ; Origin of Life ; Oxygen/chemistry/metabolism ; Photosynthesis ; Phytoplankton/*physiology ; Seawater/chemistry ; Solar System ; Solubility ; }, abstract = {Several severe glaciations occurred during the Neoproterozoic eon, and especially near its end in the Cryogenian period (630-850 Ma). While the glacial periods themselves were probably related to the continental positions being appropriate for glaciation, the general coldness of the Neoproterozoic and Cryogenian as a whole lacks specific explanation. The Cryogenian was immediately followed by the Ediacaran biota and Cambrian Metazoan, thus understanding the climate-biosphere interactions around the Cryogenian period is central to understanding the development of complex multicellular life in general. Here we present a feedback mechanism between growth of eukaryotic algal phytoplankton and climate which explains how the Earth system gradually entered the Cryogenian icehouse from the warm Mesoproterozoic greenhouse. The more abrupt termination of the Cryogenian is explained by the increase in gaseous carbon release caused by the more complex planktonic and benthic foodwebs and enhanced by a diversification of metazoan zooplankton and benthic animals. The increased ecosystem complexity caused a decrease in organic carbon burial rate, breaking the algal-climatic feedback loop of the earlier Neoproterozoic eon. Prior to the Neoproterozoic eon, eukaryotic evolution took place in a slow timescale regulated by interior cooling of the Earth and solar brightening. Evolution could have proceeded faster had these geophysical processes been faster. Thus, complex life could theoretically also be found around stars that are more massive than the Sun and have main sequence life shorter than 10 Ga. We also suggest that snow and glaciers are, in a statistical sense, important markers for conditions that may possibly promote the development of complex life on extrasolar planets.}, } @article {pmid17296731, year = {2007}, author = {Sakwe, AM and Nguyen, T and Athanasopoulos, V and Shire, K and Frappier, L}, title = {Identification and characterization of a novel component of the human minichromosome maintenance complex.}, journal = {Molecular and cellular biology}, volume = {27}, number = {8}, pages = {3044-3055}, pmid = {17296731}, issn = {0270-7306}, support = {84306//Canadian Institutes of Health Research/Canada ; }, mesh = {Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Carrier Proteins/chemistry/genetics/*metabolism ; Cell Cycle Proteins/genetics/metabolism ; Chromatin/metabolism ; DNA Helicases/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Down-Regulation/genetics ; G1 Phase ; Gene Silencing ; HeLa Cells ; Humans ; Immunoprecipitation ; Minichromosome Maintenance Complex Component 4 ; Minichromosome Maintenance Complex Component 6 ; Minichromosome Maintenance Complex Component 7 ; Molecular Sequence Data ; Multiprotein Complexes/*chemistry/*metabolism ; Nuclear Proteins/chemistry/genetics/*metabolism ; Protein Binding ; Protein Transport ; Recombinant Proteins/metabolism ; Replication Origin ; Sequence Analysis, Protein ; }, abstract = {Minichromosome maintenance (MCM) complex replicative helicase complexes play essential roles in DNA replication in all eukaryotes. Using a tandem affinity purification-tagging approach in human cells, we discovered a form of the MCM complex that contains a previously unstudied protein, MCM binding protein (MCM-BP). MCM-BP is conserved in multicellular eukaryotes and shares limited homology with MCM proteins. MCM-BP formed a complex with MCM3 to MCM7, which excluded MCM2; and, conversely, hexameric complexes of MCM2 to MCM7 lacked MCM-BP, indicating that MCM-BP can replace MCM2 in the MCM complex. MCM-BP-containing complexes exhibited increased stability under experimental conditions relative to those containing MCM2. MCM-BP also formed a complex with the MCM4/6/7 core helicase in vitro, but, unlike MCM2, did not inhibit this helicase activity. A proportion of MCM-BP bound to cellular chromatin in a cell cycle-dependent manner typical of MCM proteins, and, like other MCM subunits, preferentially associated with a cellular origin in G(1) but not in S phase. In addition, down-regulation of MCM-BP decreased the association of MCM4 with chromatin, and the chromatin association of MCM-BP was at least partially dependent on MCM4 and cdc6. The results indicate that multicellular eukaryotes contain two types of hexameric MCM complexes with unique properties and functions.}, } @article {pmid17295128, year = {2007}, author = {Yan, H and Jiang, J}, title = {Rice as a model for centromere and heterochromatin research.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {15}, number = {1}, pages = {77-84}, pmid = {17295128}, issn = {0967-3849}, mesh = {Centromere/*genetics ; Epigenesis, Genetic ; Evolution, Molecular ; *Gene Expression Regulation, Plant ; Heterochromatin/*metabolism/ultrastructure ; Histones/metabolism ; *Models, Genetic ; Oryza/*genetics/metabolism ; Transcription, Genetic ; }, abstract = {Rice (Oryza sativa) has become an important model plant species in numerous research projects involving genome, molecular and evolutionary biology. In this review we describe the reasons why rice provides an excellent model system for centromere and heterochromatin research. In most multicellular eukaryotes, centromeres and heterochromatic domains contain long arrays of repetitive DNA elements that are recalcitrant to DNA sequencing. In contrast, three rice centromeres and the majority of the cytologically defined heterochromatin in the rice genome have been sequenced to high quality, providing an unparalleled resource compared to other model multicellular eukaryotes. Most importantly, active genes have been discovered in the functional domains of several rice centromeres. The centromeric genes and sequence resources provide an unprecedented opportunity to study function and evolution of centromeres and centromere-associated genes.}, } @article {pmid17294251, year = {2008}, author = {Zhu, L and Song, L and Zhang, H and Zhao, J and Li, C and Xu, W}, title = {Molecular cloning and responsive expression to injury stimulus of a defender against cell death 1 (DAD1) gene from bay scallops Argopecten irradians.}, journal = {Molecular biology reports}, volume = {35}, number = {2}, pages = {125-132}, pmid = {17294251}, issn = {0301-4851}, mesh = {Amino Acid Sequence ; Animals ; Apoptosis Regulatory Proteins/chemistry/*genetics ; Base Sequence ; Cloning, Molecular ; Gene Expression Profiling ; Gene Expression Regulation ; Molecular Sequence Data ; Muscles/*pathology ; Pectinidae/*genetics ; Phylogeny ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Alignment ; }, abstract = {Apoptosis is an active process of cell death, which is an integral part of growth and development in multicellular organisms. The defender against cell death 1 (DAD1), the regulatory protein to inhibit the apoptosis process, was first cloned from the bay scallop Argopecten irradians by randomly sequencing a whole tissue cDNA library and rapid amplification of cDNA end (RACE). The full-length cDNA of the A. irradians DAD1 was 607 bp, consist of a 5'-terminal untranslated region (UTR) of 63 bp, a 3'-terminal UTR of 205 bp with a canonical polyadenylation signal sequence AATAAA and a poly (A) tail, and an open reading frame of 339 bp. The deduced amino acid sequence of the A. irradians DAD1 showed 75.5% identity to Araneus ventricosus, 74.5% to Drosophila melanogaster, and 73.6% to Homo sapiens, Sus scrofa, Mesocricetus auratus, Rattus norvegicus and Mus musculus. Excluding the Saccharomyces cerevisiae DAD1 homologue, all animal DAD1 including A. irradians DAD1 homologue formed a subgroup and all plant DAD1 proteins formed another subgroup in the phylogenetic analysis. The A. irradians DAD1 was expressed in all examined tissues including adductor muscle, mantle, gills, digestive gland, gonad and hemolymph, suggesting that A. irradians DAD1 is expressed in most body tissues. Furthermore, the mRNA expression levels of A. irradians DAD1 gene of hemolymph were particularly high after injury, suggesting that the gene is responsive to injury stimuli.}, } @article {pmid17293029, year = {2007}, author = {Yoshida, H and Anai, H and Horimoto, K}, title = {Derivation of rigorous conditions for high cell-type diversity by algebraic approach.}, journal = {Bio Systems}, volume = {90}, number = {2}, pages = {486-495}, doi = {10.1016/j.biosystems.2006.11.008}, pmid = {17293029}, issn = {0303-2647}, mesh = {Algorithms ; Animals ; Biological Evolution ; Cell Aggregation ; Cell Differentiation ; Cell Division ; Cell Physiological Phenomena ; Cell Proliferation ; Computer Simulation ; *Genetic Variation ; Models, Biological ; Models, Statistical ; Models, Theoretical ; Systems Biology ; }, abstract = {The development of a multicellular organism is a dynamic process. Starting with one or a few cells, the organism develops into different types of cells with distinct functions. We have constructed a simple model by considering the cell number increase and the cell-type order conservation, and have assessed conditions for cell-type diversity. This model is based on a stochastic Lindenmayer system with cell-to-cell interactions for three types of cells. In the present model, we have successfully derived complex but rigorous algebraic relations between the proliferation and transition rates for cell-type diversity by using a symbolic method: quantifier elimination (QE). Surprisingly, three modes for the proliferation and transition rates have emerged for large ratios of the initial cells to the developed cells. The three modes have revealed that the equality between the development rates for the highest cell-type diversity is reduced during the development process of multicellular organisms. Furthermore, we have found that the highest cell-type diversity originates from order conservation.}, } @article {pmid17276527, year = {2007}, author = {Birchler, JA and Yao, H and Chudalayandi, S}, title = {Biological consequences of dosage dependent gene regulatory systems.}, journal = {Biochimica et biophysica acta}, volume = {1769}, number = {5-6}, pages = {422-428}, pmid = {17276527}, issn = {0006-3002}, support = {R01 GM068042/GM/NIGMS NIH HHS/United States ; R01 GM068042-02/GM/NIGMS NIH HHS/United States ; }, mesh = {Aneuploidy ; Animals ; Biological Evolution ; Diploidy ; Dosage Compensation, Genetic ; Drosophila/genetics ; *Gene Dosage ; *Gene Expression Regulation ; Hybrid Vigor ; Models, Genetic ; Phenotype ; Plants/genetics ; Ploidies ; Quantitative Trait Loci ; }, abstract = {Chromatin and gene regulatory molecules tend to operate in multisubunit complexes in the process of controlling gene expression. Accumulating evidence suggests that varying the amount of any one member of such complexes will affect the function of the whole via the kinetics of assembly and other actions. In effect, they exhibit a "balance" among themselves in terms of the activity of the whole. When this fact is coupled with genetic and biological observations stretching back a century, a synthesis emerges that helps explain at least some aspects of a variety of phenomena including aneuploid syndromes, dosage compensation, quantitative trait genetics, regulatory gene evolution following polyploidization, the emergence of complexity in multicellular organisms, the genetic basis of evolutionary gradualism and potential implications for heterosis and co-evolving genes complexes involved with speciation. In this article we will summarize the evidence for this potential synthesis.}, } @article {pmid17275133, year = {2007}, author = {Ruiz-Trillo, I and Burger, G and Holland, PW and King, N and Lang, BF and Roger, AJ and Gray, MW}, title = {The origins of multicellularity: a multi-taxon genome initiative.}, journal = {Trends in genetics : TIG}, volume = {23}, number = {3}, pages = {113-118}, doi = {10.1016/j.tig.2007.01.005}, pmid = {17275133}, issn = {0168-9525}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Classification ; *Evolution, Molecular ; Fungi/classification/genetics ; Genome ; *Genome, Fungal ; *Genomics ; Models, Genetic ; *Phylogeny ; Selection, Genetic ; }, abstract = {The emergence of multicellular organisms from single-celled ancestors -- which occurred several times, independently in different branches of the eukaryotic tree -- is one of the most profound evolutionary transitions in the history of life. These events not only radically changed the course of life on Earth but also created new challenges, including the need for cooperation and communication between cells, and the division of labor among different cell types. However, the genetic changes that accompanied the several origins of multicellularity remain elusive. Recently, the National Human Genome Research Institute (NHGRI) endorsed a multi-taxon genome-sequencing initiative that aims to gain insights into how multicellularity first evolved. This initiative (which we have termed UNICORN) will generate extensive genomic data from some of the closest extant unicellular relatives of both animals and fungi. Here, we introduce this initiative and the biological questions that underpin it, summarize the rationale guiding the choice of organisms and discuss the anticipated benefits to the broader scientific community.}, } @article {pmid17275131, year = {2007}, author = {Ma, J and Wing, RA and Bennetzen, JL and Jackson, SA}, title = {Plant centromere organization: a dynamic structure with conserved functions.}, journal = {Trends in genetics : TIG}, volume = {23}, number = {3}, pages = {134-139}, doi = {10.1016/j.tig.2007.01.004}, pmid = {17275131}, issn = {0168-9525}, mesh = {Centromere/*chemistry/metabolism ; Chromatin/chemistry ; Chromosomes, Plant/*chemistry/metabolism ; DNA, Plant/metabolism ; DNA, Satellite/metabolism ; Epigenesis, Genetic ; *Evolution, Molecular ; Gene Rearrangement ; Models, Genetic ; Oryza/genetics ; Plants/*genetics ; *Recombination, Genetic ; }, abstract = {Although the structural features of centromeres from most multicellular eukaryotes remain to be characterized, recent analyses of the complete sequences of two centromeric regions of rice, together with data from Arabidopsis thaliana and maize, have illuminated the considerable size variation and sequence divergence of plant centromeres. Despite the severe suppression of meiotic chromosomal exchange in centromeric and pericentromeric regions of rice, the centromere core shows high rates of unequal homologous recombination in the absence of chromosomal exchange, resulting in frequent and extensive DNA rearrangement. Not only is the sequence of centromeric tandem and non-tandem repeats highly variable but also the copy number, spacing, order and orientation, providing ample natural variation as the basis for selection of superior centromere performance. This review article focuses on the structural and evolutionary dynamics of plant centromere organization and the potential molecular mechanisms responsible for the rapid changes of centromeric components.}, } @article {pmid17272304, year = {2007}, author = {Kapraun, DF}, title = {Nuclear DNA content estimates in green algal lineages: chlorophyta and streptophyta.}, journal = {Annals of botany}, volume = {99}, number = {4}, pages = {677-701}, pmid = {17272304}, issn = {0305-7364}, mesh = {Cell Nucleus/genetics ; Chlorophyta/*classification/genetics ; DNA, Algal/*analysis ; Microspectrophotometry ; *Phylogeny ; }, abstract = {BACKGROUND AND AIMS: Consensus higher-level molecular phylogenies present a compelling case that an ancient divergence separates eukaryotic green algae into two major monophyletic lineages, Chlorophyta and Streptophyta, and a residuum of green algae, which have been referred to prasinophytes or micromonadophytes. Nuclear DNA content estimates have been published for less than 1% of the described green algal members of Chlorophyta, which includes multicellular green marine algae and freshwater flagellates (e.g. Chlamydomonas and Volvox). The present investigation summarizes the state of our knowledge and adds substantially to our database of C-values, especially for the streptophyte charophycean lineage which is the sister group of the land plants. A recent list of 2C nuclear DNA contents for isolates and species of green algae is expanded by 72 to 157.

METHODS: The DNA-localizing fluorochrome DAPI (4',6-diamidino-2-phenylindole) and red blood cell (chicken erythrocytes) standard were used to estimate 2C values with static microspectrophotometry.

KEY RESULTS: In Chlorophyta, including Chlorophyceae, Prasinophyceae, Trebouxiophyceae and Ulvophyceae, 2C DNA estimates range from 0.01 to 5.8 pg. Nuclear DNA content variation trends are noted and discussed for specific problematic taxon pairs, including Ulotrichales-Ulvales, and Cladophorales-Siphonocladales. For Streptophyta, 2C nuclear DNA contents range from 0.2 to 6.4 pg, excluding the highly polyploid Charales and Desmidiales, which have genome sizes of up to 14.8 and 46.8 pg, respectively. Nuclear DNA content data for Streptophyta superimposed on a contemporary molecular phylogeny indicate that early diverging lineages, including some members of Chlorokybales, Coleochaetales and Klebsormidiales, have genomes as small as 0.1-0.5 pg. It is proposed that the streptophyte ancestral nuclear genome common to both the charophyte and the embryophyte lineages can be characterized as 1C = 0.2 pg and 1n = 6.

CONCLUSIONS: These data will help pre-screen candidate species for the on-going construction of bacterial artificial chromosome nuclear genome libraries for land plant ancestors. Data for the prasinophyte Mesostigma are of particular interest as this alga reportedly most closely resembles the 'ancestral green flagellate'. Both mechanistic and ecological processes are discussed that could have produced the observed C-value increase of >100-fold in the charophyte green algae whereas the ancestral genome was conserved in the embryophytes.}, } @article {pmid17267602, year = {2007}, author = {Shou, W and Ram, S and Vilar, JM}, title = {Synthetic cooperation in engineered yeast populations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {104}, number = {6}, pages = {1877-1882}, pmid = {17267602}, issn = {0027-8424}, mesh = {Ecology ; *Models, Genetic ; Organisms, Genetically Modified/*physiology ; Saccharomyces cerevisiae/cytology/*genetics/growth & development/physiology ; Symbiosis/*genetics/physiology ; }, abstract = {Cooperative interactions are key to diverse biological phenomena ranging from multicellularity to mutualism. Such diversity makes the ability to create and control cooperation desirable for potential applications in areas as varied as agriculture, pollutant treatment, and medicine. Here we show that persistent cooperation can be engineered by introducing a small set of genetic modifications into previously noninteracting cell populations. Specifically, we report the construction of a synthetic obligatory cooperative system, termed CoSMO (cooperation that is synthetic and mutually obligatory), which consists of a pair of nonmating yeast strains, each supplying an essential metabolite to the other strain. The behavior of the two strains in isolation, however, revealed unintended constraints that restrict cooperation, such as asymmetry in starvation tolerance and delays in nutrient release until near cell death. However, the joint system is shown mathematically and experimentally to be viable over a wide range of initial conditions, with oscillating population ratio settling to a value predicted by nutrient supply and consumption. Unexpectedly, even in the absence of explicitly engineered mechanisms to stabilize cooperation, the cooperative system can consistently develop increased ability to survive reductions in population density. Extending synthetic biology from the design of genetic circuits to the engineering of ecological interactions, CoSMO provides a quantitative system for linking processes at the cellular level to the collective behavior at the system level, as well as a genetically tractable system for studying the evolution of cooperation.}, } @article {pmid17257913, year = {2007}, author = {Tamerler, C and Sarikaya, M}, title = {Molecular biomimetics: utilizing nature's molecular ways in practical engineering.}, journal = {Acta biomaterialia}, volume = {3}, number = {3}, pages = {289-299}, doi = {10.1016/j.actbio.2006.10.009}, pmid = {17257913}, issn = {1742-7061}, mesh = {*Biomedical Engineering ; *Biomimetics ; Forecasting ; *Genetic Engineering ; *Nanotechnology ; *Nature ; }, abstract = {In nature, proteins are the machinery that accomplish many functions through their specific recognition and interactions in biological systems from single-celled to multicellular organisms. Biomolecule-material interaction is accomplished via molecular specificity, leading to the formation of controlled structures and functions at all scales of dimensional hierarchy. Through evolution, molecular recognition and, consequently, functions developed through successive cycles of mutation and selection. Using biology as a guide, we can now understand, engineer and control peptide-material interactions and exploit these to tailor novel materials and systems for practical applications. We adapted combinatorial biology protocols to display peptide libraries, either on the cell surface or on phages, to select short peptides specific to a variety of practical materials systems. Following the selection step, we determined the kinetics and stability of peptide binding experimentally to understand the bound peptide structure via modeling and its assembly via atomic force microscopy. The peptides were further engineered to have multiple repeats or their amino acid sequences varied to tailor their function. Both nanoparticles and flat inorganic substrates containing multimaterials patterned at the nano- and microscales were used for self-directed immobilization of molecular constructs. The molecular biomimetic approach opens up new avenues for the design and utilization of multifunctional molecular systems with wide ranging applications, from tissue engineering, drug delivery and biosensors, to nanotechnology and bioremediation. Here we give examples of protein-mediated functional materials in biology, peptide selection and engineering with affinity to inorganics, demonstrate potential utilizations in materials science, engineering and medicine, and describe future prospects.}, } @article {pmid17237137, year = {2007}, author = {Bishop, JR and Gagneux, P}, title = {Evolution of carbohydrate antigens--microbial forces shaping host glycomes?.}, journal = {Glycobiology}, volume = {17}, number = {5}, pages = {23R-34R}, doi = {10.1093/glycob/cwm005}, pmid = {17237137}, issn = {0959-6658}, mesh = {Animals ; Bacteria/*immunology ; *Evolution, Molecular ; Fungi/*immunology ; Host-Parasite Interactions/*immunology ; Parasites/*immunology ; Polysaccharides/*immunology ; *Selection, Genetic ; Symbiosis/immunology ; }, abstract = {Many glycans show remarkably discontinuous distribution across evolutionary lineages. These differences play major roles when organisms belonging to different lineages interact as host-pathogen or host-symbiont. Certain lineage-specific glycans have become important signals for multicellular host organisms, which use them as molecular signatures of their pathogens and symbionts through recognition by a toolkit of innate defense molecules. In turn, pathogens have evolved to exploit host lineage-specific glycans and are constantly shaping the glycomes of their hosts. These interactions take place in the face of numerous critical endogenous functions played by glycans within host organisms. Whether due to simple evolutionary divergence or adaptive changes under natural selection resulting from endogenous functional requirements, once different lineages elaborate on differential glycomes these mutual differences provide opportunities for host exploitation and/or pathogen defense between lineages. Such phylogenetic molecular recognition mechanisms will augment and likely contribute to the maintenance of lineage-specific differences in glycan repertoires.}, } @article {pmid17233593, year = {2007}, author = {Michell, RH}, title = {Evolution of the diverse biological roles of inositols.}, journal = {Biochemical Society symposium}, volume = {}, number = {74}, pages = {223-246}, doi = {10.1042/BSS0740223}, pmid = {17233593}, issn = {0067-8694}, mesh = {*Biological Evolution ; Models, Biological ; Phosphatidylinositols/chemistry/*metabolism ; }, abstract = {Several of the nine hexahydroxycylohexanes (inositols) have functions in Biology, with myo-inositol (Ins) in most of the starring roles; and Ins polyphosphates are amongst the most abundant organic phosphate constituents on Earth. Many Archaea make Ins and use it as a component of diphytanyl membrane phospholipids and the thermoprotective solute di-L-Ins-1,1'-phosphate. Few bacteria make Ins or use it, other than as a carbon source. Those that do include hyperthermophilic Thermotogales (which also employ di-L-Ins-1,1'-phosphate) and actinomycetes such as Mycobacterium spp. (which use mycothiol, an inositol-containing thiol, as an intracellular redox reagent and have characteristic phosphatidylinositol-linked surface oligosaccharides). Bacteria acquired their Ins3P synthases by lateral gene transfer from Archaea. Many eukaryotes, including stressed plants, insects, deep-sea animals and kidney tubule cells, adapt to environmental variation by making or accumulating diverse inositol derivatives as 'compatible' solutes. Eukaryotes use phosphatidylinositol derivatives for numerous roles in cell signalling and regulation and in protein anchoring at the cell surface. Remarkably, the diradylglycerol cores of archaeal and eukaryote/bacterial glycerophospholipids have mirror image configurations: sn-2,3 and sn-1,2 respectively. Multicellular animals and amoebozoans exhibit the greatest variety of functions for PtdIns derivatives, including the use of PtdIns(3,4,5)P3 as a signal. Evolutionarily, it seems likely that (i) early archaeons first made myo-inositol approx. 3500 Ma (million years) ago; (ii) archeons brought inositol derivatives into early eukaryotes (approx. 2000 Ma?); (iii) soon thereafter, eukaryotes established ubiquitous functions for phosphoinositides in membrane trafficking and Ins polyphosphate synthesis; and (iv) since approx. 1000 Ma, further waves of functional diversification in amoebozoans and metazoans have introduced Ins(1,4,5)P3 receptor Ca2+ channels and the messenger role of PtdIns(3,4,5)P3.}, } @article {pmid17222528, year = {2007}, author = {Huang, ZP and Chen, CJ and Zhou, H and Li, BB and Qu, LH}, title = {A combined computational and experimental analysis of two families of snoRNA genes from Caenorhabditis elegans, revealing the expression and evolution pattern of snoRNAs in nematodes.}, journal = {Genomics}, volume = {89}, number = {4}, pages = {490-501}, doi = {10.1016/j.ygeno.2006.12.002}, pmid = {17222528}, issn = {0888-7543}, mesh = {Animals ; Caenorhabditis elegans/*genetics ; Genetic Variation ; Genomics/methods ; Introns/genetics ; Nematoda/genetics ; RNA Splice Sites ; RNA, Small Nucleolar/*genetics ; Software ; }, abstract = {Small nucleolar RNAs (snoRNAs) are an abundant group of noncoding RNAs mainly involved in the posttranscriptional modifications of rRNAs in eukaryotes. Prior to this study, only 28 snoRNA genes had been identified from Caenorhabditis elegans, indicating that most snoRNA genes are hidden in the worm genome, which represents a simple multicellular metazoan. In this study, a genome-wide analysis of the two major families of snoRNA genes in C. elegans was performed using the snoscan and snoGPS programs incorporating comparative genome analyses. Seventy gene variants, including 36 box C/D and 34 box H/ACA snoRNA genes, were identified, of which 50 are novel. Two families of snoRNAs showed a characteristic genomic organization. Notably, 6 box C/D snoRNA genes were located in the antisense orientation of introns. In contrast to insect and mammal, the distances between many intronic snoRNAs and 3' splice sites of introns were less than 50 nt in the worm, an unexpected finding as intron-encoded snoRNAs in C. elegans are supposed to be expressed in a splicing-dependent pathway. Interestingly, a canonical H/ACA snoRNA, PsiCeU5-48, was revealed to be partially homologous to small Cajal body-specific RNA (scaRNA) U85 and U89 in fly and human, indicating a possible evolutionary relationship between snoRNAs and scaRNAs.}, } @article {pmid17215372, year = {2007}, author = {Savage, VM and West, GB}, title = {A quantitative, theoretical framework for understanding mammalian sleep.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {104}, number = {3}, pages = {1051-1056}, pmid = {17215372}, issn = {0027-8424}, support = {P50 GM068763/GM/NIGMS NIH HHS/United States ; 1P50 GM 68763-02/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Mammals ; Models, Biological ; Sleep/*physiology ; Time Factors ; }, abstract = {Sleep is one of the most noticeable and widespread phenomena occurring in multicellular animals. Nevertheless, no consensus for a theory of its origins has emerged. In particular, no explicit, quantitative theory exists that elucidates or distinguishes between the myriad hypotheses proposed for sleep. Here, we develop a general, quantitative theory for mammalian sleep that relates many of its fundamental parameters to metabolic rate and body size. Several mechanisms suggested for the function of sleep can be placed in this framework, e.g., cellular repair of damage caused by metabolic processes as well as cortical reorganization to process sensory input. Our theory leads to predictions for sleep time, sleep cycle time, and rapid eye movement time as functions of body and brain mass, and it explains, for example, why mice sleep approximately 14 hours per day relative to the 3.5 hours per day that elephants sleep. Data for 96 species of mammals, spanning six orders of magnitude in body size, are consistent with these predictions and provide strong evidence that time scales for sleep are set by the brain's, not the whole-body, metabolic rate.}, } @article {pmid17210927, year = {2007}, author = {Pennacchio, LA and Loots, GG and Nobrega, MA and Ovcharenko, I}, title = {Predicting tissue-specific enhancers in the human genome.}, journal = {Genome research}, volume = {17}, number = {2}, pages = {201-211}, pmid = {17210927}, issn = {1088-9051}, support = {R01 HG003988/HG/NHGRI NIH HHS/United States ; HL066681/HL/NHLBI NIH HHS/United States ; HG003988/HG/NHGRI NIH HHS/United States ; R01 HG003963/HG/NHGRI NIH HHS/United States ; R01 HG003963-01A2/HG/NHGRI NIH HHS/United States ; U01 HL066681/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Enhancer Elements, Genetic ; Female ; Gene Expression Profiling ; *Genome, Human ; Humans ; Liver/metabolism ; Male ; Muscle, Skeletal/metabolism ; Pregnancy ; Species Specificity ; Tissue Distribution ; Transcription Factors/genetics ; Vertebrates/genetics ; }, abstract = {Determining how transcriptional regulatory signals are encoded in vertebrate genomes is essential for understanding the origins of multicellular complexity; yet the genetic code of vertebrate gene regulation remains poorly understood. In an attempt to elucidate this code, we synergistically combined genome-wide gene-expression profiling, vertebrate genome comparisons, and transcription factor binding-site analysis to define sequence signatures characteristic of candidate tissue-specific enhancers in the human genome. We applied this strategy to microarray-based gene expression profiles from 79 human tissues and identified 7187 candidate enhancers that defined their flanking gene expression, the majority of which were located outside of known promoters. We cross-validated this method for its ability to de novo predict tissue-specific gene expression and confirmed its reliability in 57 of the 79 available human tissues, with an average precision in enhancer recognition ranging from 32% to 63% and a sensitivity of 47%. We used the sequence signatures identified by this approach to successfully assign tissue-specific predictions to approximately 328,000 human-mouse conserved noncoding elements in the human genome. By overlapping these genome-wide predictions with a data set of enhancers validated in vivo, in transgenic mice, we were able to confirm our results with a 28% sensitivity and 50% precision. These results indicate the power of combining complementary genomic data sets as an initial computational foray into a global view of tissue-specific gene regulation in vertebrates.}, } @article {pmid17208234, year = {2007}, author = {Zhang, S and Sakuradani, E and Ito, K and Shimizu, S}, title = {Identification of a novel bifunctional delta12/delta15 fatty acid desaturase from a basidiomycete, Coprinus cinereus TD#822-2.}, journal = {FEBS letters}, volume = {581}, number = {2}, pages = {315-319}, doi = {10.1016/j.febslet.2006.12.031}, pmid = {17208234}, issn = {0014-5793}, mesh = {Cloning, Molecular ; Coprinus/*enzymology/genetics ; Fatty Acid Desaturases/classification/*genetics/*metabolism ; Fatty Acids/analysis/biosynthesis ; Phylogeny ; Saccharomyces cerevisiae/genetics ; }, abstract = {A new gene encoding a delta12 fatty acid desaturase-related protein was cloned from a multicellular basidiomycete Coprinus cinereus TD#822-2. The 1326 bp full-length gene, designated as Cop-odeA, codes for a putative protein of 442 amino acids with a MW of 49224. The Cop-odeA yeast transformant accumulated four new fatty acids identified as 9,12-hexadecadienoic acid, 9,12,15-hexadecatrienoic acid, linoleic acid, and alpha-linolenic acid, which comprised 8.8%, 1.0%, 29.0%, and 0.6% of the total fatty acids, respectively. The Cop-odeA protein was confirmed to be a novel bifunctional fatty acid desaturase with both high delta12 desaturase activity and unusual delta15 desaturase activity.}, } @article {pmid17207937, year = {2007}, author = {Lyu, BN and Lyu, MB and Ismailov, BI and Ismailov, SB}, title = {Four hypotheses on mitochondria's role in the development and regulation of oxidative stress in the normal state, cell pathology and reversion of tumor cells.}, journal = {Medical hypotheses}, volume = {69}, number = {1}, pages = {186-194}, doi = {10.1016/j.mehy.2006.10.055}, pmid = {17207937}, issn = {0306-9877}, mesh = {Animals ; Humans ; Mitochondria/*metabolism ; *Models, Biological ; Neoplasms/*metabolism ; *Oxidative Stress ; Oxygen/*metabolism ; *Oxygen Consumption ; }, abstract = {The biological evolution has resulted in adaptation of both unicellular and multicellular organisms to negative effect of excessive O2 in reply to gradual increase of free oxygen (O2) contents in the earth atmosphere. This adaptation has led to formation of various antioxidant systems in the organism. Such system within the cell has hierarchic structure and is represented by at least than three levels of protection: antioxygene, antiradical and antiperoxide. The first and most effective antioxidant level is represented as mitochondrial respiration able to perform several functions. One of these functions is antioxygene since the very the mitochondria's capability to be a main O2 consumer in the cell provides for low but sufficient for respiration and energy supply levels of O2 partial pressure and dependent concentrations of active O2 forms. The latters, being signal molecules at certain values, modify regular and synthetic processes in the cells either directly or indirectly. This is the possibility for mitochondria to more extensively affect the intracellular processes than simply produce ATP. In case of defective of the cell first protection line the hyperoxia starts due to poor utilization of the incoming O2. Change in mitochondria's "capacity" (quantity, size and maturity level of mitochondria) anyway occurring in the cells are an efficient way of regulation of the oxy-peroxide condition (oxidative stress) and related signal channels. The relationship between changes in the condition of cells, i.e. from their normal state to different pathologic forms, and growing disbalance Delta(PO-AO) between its pro-oxygen (PO) and anti-oxygen (AO) components has been assumed. It is expected that during the evolution the cell could have supposedly acquired a sequence of "specialized" Delta(PO-AO) disbalances. Each sequence needs to implement a certain set of biochemical processes. The probability of Delta(PO-AO) disbalance gradation with specification of their value ranges has been determined. These ranges identify or impact certain cell state, namely proliferation of normal cell (oxidative mitogenesis), ageing, A1 apoptosis, carcinogenesis, A2 apoptosis, and oxidative cytolysis. The cited assumption allows us to: (1) explain reverse dependence of cell proliferation due to the level of their differentiation, increase in the amount and activity of mitochondria as an indispensable condition for the disbalance shift towards differentiation, (2) bring up the idea that regress of the cells, and in particular tumour cells, directly results from the Delta(PO-AO) disbalance decrease to certain levels under the influence of reverse inductors, (3) explain relatively easy and frequent embryonic and stem cells malignancy, and also their reversal normalization. These phenomena occur due to small number and/or size of mitochondria in the designated cells. To verify the above mentioned hypotheses it is primarily necessary to be able to stimulate and slow down the mitochondria biogenesis in the embryonic, stem, ageing, cancer and other cells.}, } @article {pmid17204477, year = {2007}, author = {Zhang, X and Boot-Handford, RP and Huxley-Jones, J and Forse, LN and Mould, AP and Robertson, DL and Lili, and Athiyal, M and Sarras, MP}, title = {The collagens of hydra provide insight into the evolution of metazoan extracellular matrices.}, journal = {The Journal of biological chemistry}, volume = {282}, number = {9}, pages = {6792-6802}, doi = {10.1074/jbc.M607528200}, pmid = {17204477}, issn = {0021-9258}, support = {DK065123/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; *Biological Evolution ; Extracellular Matrix/chemistry/*genetics ; Fibrillar Collagens/chemistry/*genetics ; Hydra/*genetics ; Phylogeny ; Protein Conformation ; von Willebrand Factor ; }, abstract = {A collagen-based extracellular matrix is one defining feature of all Metazoa. The thick sheet-like extracellular matrix (mesoglia) of the diploblast, hydra, has characteristics of both a basement membrane and an interstitial matrix. Several genes associated with mesoglea have been cloned including a basement membrane and fibrillar collagen and an A and B chain of laminin. Here we report the characterization of a further three fibrillar collagen genes (Hcol2, Hcol3, and Hcol5) and the partial sequence of a collagen gene with a unique structural organization consisting of multiple von Willebrand factor A domains interspersed with interrupted collagenous triple helices (Hcol6) from Hydra vulgaris. Hcol2 and -5 have major collagenous domains of classical length (approximately 1020 amino acid residues), whereas the equivalent domain in Hcol3 is shorter (969 residues). The N-propeptide of Hcol2 contains a whey acid protein four-cysteine repeat (WAP) domain, and the equivalent domain of Hcol3 contains two WAP and two von Willebrand factor A domains. Phylogenetic analyses reveal that the hydra fibrillar collagen genes form a distinct clade that appears related to the protostome/deuterostome A clade of fibrillar collagens. Data base searches reveal Hcol2, -5, and -6 are highly conserved in Hydra magnipapillata, which also provided preliminary evidence for the expression of a B-clade fibrillar collagen. All four of the H. vulgaris collagens are expressed specifically by the ectoderm. The expression pattern for Hcol2 is similar to that previously reported for Hcol1 (Deutzmann, R., Fowler, S., Zhang, X., Boone, K., Dexter, S., Boot-Handford, R. P., Rachel, R., and Sarras, M. P., Jr. (2000) Development 127, 4669-4680) but distinct from the pattern shared by Hcol3 and Hcol5. The characterization of multiple collagen genes in relatively simple diploblastic organisms provides new insights into the molecular evolution of collagens and the origins of the collagen-based extracellular matrix found throughout the multicellular animal kingdom.}, } @article {pmid17197196, year = {2007}, author = {Böttger, A and Alexandrova, O}, title = {Programmed cell death in Hydra.}, journal = {Seminars in cancer biology}, volume = {17}, number = {2}, pages = {134-146}, doi = {10.1016/j.semcancer.2006.11.008}, pmid = {17197196}, issn = {1044-579X}, mesh = {Animals ; Apoptosis/*physiology ; Hydra/cytology/*physiology ; Phagocytosis ; }, abstract = {Hydra is one of the simplest metazoans and thus an important model organism for studies on the evolution of developmental mechanisms in multi-cellular animals. In Hydra apoptosis is involved in the regulation of cell numbers in response to feeding, in regeneration and in the removal of non-self cells. It also participates in the maintenance of cellular homeostasis in germ cells. During oogenesis a special "arrested" apoptosis of nurse cells is observed. The morphology of apoptotic hydra cells is almost indistinguishable from apoptosis in higher animals and caspases as well as members of the Bcl-2 family participate in the process.}, } @article {pmid19468312, year = {2007}, author = {Vitulo, N and Vezzi, A and Galla, G and Citterio, S and Marino, G and Ruperti, B and Zermiani, M and Albertini, E and Valle, G and Barcaccia, G}, title = {Characterization and evolution of the cell cycle-associated mob domain-containing proteins in eukaryotes.}, journal = {Evolutionary bioinformatics online}, volume = {3}, number = {}, pages = {121-158}, pmid = {19468312}, issn = {1176-9343}, abstract = {The MOB family includes a group of cell cycle-associated proteins highly conserved throughout eukaryotes, whose founding members are implicated in mitotic exit and co-ordination of cell cycle progression with cell polarity and morphogenesis. Here we report the characterization and evolution of the MOB domain-containing proteins as inferred from the 43 eukaryotic genomes so far sequenced. We show that genes for Mob-like proteins are present in at least 41 of these genomes, confirming the universal distribution of this protein family and suggesting its prominent biological function. The phylogenetic analysis reveals five distinct MOB domain classes, showing a progressive expansion of this family from unicellular to multicellular organisms, reaching the highest number in mammals. Plant Mob genes appear to have evolved from a single ancestor, most likely after the loss of one or more genes during the early stage of Viridiplantae evolutionary history. Three of the Mob classes are widespread among most of the analyzed organisms. The possible biological and molecular function of Mob proteins and their role in conserved signaling pathways related to cell proliferation, cell death and cell polarity are also presented and critically discussed.}, } @article {pmid17190971, year = {2007}, author = {Wiens, M and Korzhev, M and Perovic-Ottstadt, S and Luthringer, B and Brandt, D and Klein, S and Müller, WE}, title = {Toll-like receptors are part of the innate immune defense system of sponges (demospongiae: Porifera).}, journal = {Molecular biology and evolution}, volume = {24}, number = {3}, pages = {792-804}, doi = {10.1093/molbev/msl208}, pmid = {17190971}, issn = {0737-4038}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Northern ; Caspases/genetics/immunology ; Cluster Analysis ; Croatia ; DNA Primers ; Immunity, Innate/*genetics ; Immunohistochemistry ; In Situ Hybridization ; Interleukin-1 Receptor-Associated Kinases/genetics/immunology ; Molecular Sequence Data ; *Phylogeny ; Porifera/*genetics/immunology ; Sequence Analysis, DNA ; Toll-Like Receptors/*genetics/immunology ; }, abstract = {During evolution and with the emergence of multicellular animals, the need arose to ward off foreign organisms that threaten the integrity of the animal body. Among many different receptors that participate in the recognition of microbial invaders, toll-like receptors (TLRs) play an essential role in mediating the innate immune response. After binding distinct microbial components, TLRs activate intracellular signaling cascades that result in an induced expression of diverse antimicrobial molecules. Because sponges (phylum Porifera) are filter feeders, they are abundantly exposed to microorganisms that represent a potential threat. Here, we describe the identification, cloning, and deduced protein sequence from 3 major elements of the poriferan innate response (to bacterial lipopeptides): the TLR, the IL-1 receptor-associated kinase-4-like protein (IRAK-4l), and a novel effector caspase from the demosponge Suberites domuncula. Each molecule shares significant sequence similarity with its homologues in higher Metazoa. Sequence homologies were found in particular within the family-specific domains toll/interleukin-1 receptor/resistance (TLR family), Ser/Thr/Tyr kinase domain (IRAK family), and CASc (caspase family). In addition, in situ hybridization and immunohistological analyses revealed an abundance of SDTLR (TLR) transcripts in epithelial layers of the sponge surface (exopinacoderm and endopinacoderm). Furthermore, it is shown that both SDTLR and SDIRAK-4 like (IRAK) are expressed constitutively, regardless of treatment with synthetic triacyl lipopeptide Pam(3)Cys-Ser-(Lys)(4). In contrast, SDCASL (caspase) expression is highly Pam(3)Cys-Ser-(Lys)(4) inducible. However, blocking of the lipopeptide with recombinant TLR prior to its application completely prevented the induced expression of this poriferan caspase. These results underscore that the phylogenetically oldest extant metazoan phylum is provided already with the signaling pathways of the antimicrobial host-defense system of Metazoa.}, } @article {pmid17174908, year = {2006}, author = {Kirk, DL}, title = {Oogamy: inventing the sexes.}, journal = {Current biology : CB}, volume = {16}, number = {24}, pages = {R1028-30}, doi = {10.1016/j.cub.2006.11.015}, pmid = {17174908}, issn = {0960-9822}, mesh = {Algal Proteins/*genetics/physiology ; Animals ; Basic-Leucine Zipper Transcription Factors/genetics/physiology ; *Biological Evolution ; Chlamydomonas reinhardtii/classification/genetics/*physiology ; *Genes ; Phylogeny ; Polymerase Chain Reaction ; Protein Structure, Tertiary ; Reproduction/genetics ; Volvox/classification/genetics/*physiology ; }, abstract = {The male-female dichotomy has evolved independently in nearly all lineages of multicellular organisms. Why this should be the case is still uncertain, but recent studies of mating-type genes in green algae open a promising new way to explore molecular-genetic aspects of the evolution of dichotomous sexes.}, } @article {pmid17173545, year = {2007}, author = {Seluanov, A and Chen, Z and Hine, C and Sasahara, TH and Ribeiro, AA and Catania, KC and Presgraves, DC and Gorbunova, V}, title = {Telomerase activity coevolves with body mass not lifespan.}, journal = {Aging cell}, volume = {6}, number = {1}, pages = {45-52}, pmid = {17173545}, issn = {1474-9718}, support = {R01 AG027237/AG/NIA NIH HHS/United States ; R01 AG027237-01A1/AG/NIA NIH HHS/United States ; R01 AG027237-02/AG/NIA NIH HHS/United States ; R01 AG027237-03/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Body Weight/*physiology ; Cellular Senescence/physiology ; Female ; Longevity/*physiology ; Male ; Mice ; Organ Specificity ; Phylogeny ; Rats ; Rats, Inbred F344 ; Rodentia/*physiology ; Species Specificity ; Telomerase/*metabolism ; Telomere/chemistry ; }, abstract = {In multicellular organisms, telomerase is required to maintain telomere length in the germline but is dispensable in the soma. Mice, for example, express telomerase in somatic and germline tissues, while humans express telomerase almost exclusively in the germline. As a result, when telomeres of human somatic cells reach a critical length the cells enter irreversible growth arrest called replicative senescence. Replicative senescence is believed to be an anticancer mechanism that limits cell proliferation. The difference between mice and humans led to the hypothesis that repression of telomerase in somatic cells has evolved as a tumor-suppressor adaptation in large, long-lived organisms. We tested whether regulation of telomerase activity coevolves with lifespan and body mass using comparative analysis of 15 rodent species with highly diverse lifespans and body masses. Here we show that telomerase activity does not coevolve with lifespan but instead coevolves with body mass: larger rodents repress telomerase activity in somatic cells. These results suggest that large body mass presents a greater risk of cancer than long lifespan, and large animals evolve repression of telomerase activity to mitigate that risk.}, } @article {pmid17166053, year = {2006}, author = {Xia, K and Xue, H and Dong, D and Zhu, S and Wang, J and Zhang, Q and Hou, L and Chen, H and Tao, R and Huang, Z and Fu, Z and Chen, YG and Han, JD}, title = {Identification of the proliferation/differentiation switch in the cellular network of multicellular organisms.}, journal = {PLoS computational biology}, volume = {2}, number = {11}, pages = {e145}, pmid = {17166053}, issn = {1553-7358}, mesh = {Animals ; Biology ; Cell Differentiation ; Cell Proliferation ; Cluster Analysis ; Computational Biology/*methods ; Databases, Genetic ; Databases, Protein ; Drosophila melanogaster ; Humans ; Phylogeny ; Proteins/*chemistry ; Proteomics/methods ; Systems Biology/*methods ; Transcription, Genetic ; }, abstract = {The protein-protein interaction networks, or interactome networks, have been shown to have dynamic modular structures, yet the functional connections between and among the modules are less well understood. Here, using a new pipeline to integrate the interactome and the transcriptome, we identified a pair of transcriptionally anticorrelated modules, each consisting of hundreds of genes in multicellular interactome networks across different individuals and populations. The two modules are associated with cellular proliferation and differentiation, respectively. The proliferation module is conserved among eukaryotic organisms, whereas the differentiation module is specific to multicellular organisms. Upon differentiation of various tissues and cell lines from different organisms, the expression of the proliferation module is more uniformly suppressed, while the differentiation module is upregulated in a tissue- and species-specific manner. Our results indicate that even at the tissue and organism levels, proliferation and differentiation modules may correspond to two alternative states of the molecular network and may reflect a universal symbiotic relationship in a multicellular organism. Our analyses further predict that the proteins mediating the interactions between these modules may serve as modulators at the proliferation/differentiation switch.}, } @article {pmid17158317, year = {2006}, author = {Nowak, MA}, title = {Five rules for the evolution of cooperation.}, journal = {Science (New York, N.Y.)}, volume = {314}, number = {5805}, pages = {1560-1563}, pmid = {17158317}, issn = {1095-9203}, support = {R01 GM078986/GM/NIGMS NIH HHS/United States ; R01 GM078986-04/GM/NIGMS NIH HHS/United States ; 1R01GM078986-01/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Community Networks ; *Cooperative Behavior ; Family ; Game Theory ; Helping Behavior ; Humans ; Mathematics ; Selection, Genetic ; }, abstract = {Cooperation is needed for evolution to construct new levels of organization. Genomes, cells, multicellular organisms, social insects, and human society are all based on cooperation. Cooperation means that selfish replicators forgo some of their reproductive potential to help one another. But natural selection implies competition and therefore opposes cooperation unless a specific mechanism is at work. Here I discuss five mechanisms for the evolution of cooperation: kin selection, direct reciprocity, indirect reciprocity, network reciprocity, and group selection. For each mechanism, a simple rule is derived that specifies whether natural selection can lead to cooperation.}, } @article {pmid17156942, year = {2007}, author = {Sessa, L and Bianchi, ME}, title = {The evolution of High Mobility Group Box (HMGB) chromatin proteins in multicellular animals.}, journal = {Gene}, volume = {387}, number = {1-2}, pages = {133-140}, doi = {10.1016/j.gene.2006.08.034}, pmid = {17156942}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Animals ; Chromatin/*genetics ; DNA-Binding Proteins/chemistry/genetics/metabolism ; Evolution, Molecular ; HMGB Proteins/*chemistry/classification/genetics/*metabolism ; Invertebrates/chemistry/genetics ; Life Cycle Stages ; Molecular Sequence Data ; Protein Conformation ; }, abstract = {Mammalian HMGB proteins are abundant chromatin components, and are characterized by the presence of 2 HMG-box domains and an acidic tail. HMG boxes are present in a large number of DNA-binding proteins, and HMGB chromatin proteins represent a small and specific subset of HMG-box proteins. The comparison of DNA sequences that code for HMG-box proteins suggests that the ancestral HMG box was coded by an intronless gene, which picked up one or more introns during its radiation. Canonical HMGB proteins are only present in multicellular animals, from sponges onwards, and appear to have arisen through the fusion of two different genes, each coding for one of the boxes. The organization of HMGB genes was very conserved during Metazoan evolution, with the only deviations appearing in Caenorhabditis and Dipteran (Drosophila and Anopheles) species.}, } @article {pmid17151665, year = {2006}, author = {Fike, DA and Grotzinger, JP and Pratt, LM and Summons, RE}, title = {Oxidation of the Ediacaran ocean.}, journal = {Nature}, volume = {444}, number = {7120}, pages = {744-747}, doi = {10.1038/nature05345}, pmid = {17151665}, issn = {1476-4687}, mesh = {Animals ; Atmosphere/chemistry ; Carbon/analysis ; Carbon Isotopes ; Geologic Sediments/chemistry ; History, Ancient ; Oceans and Seas ; Oxidation-Reduction ; Oxygen/analysis/*metabolism ; Plankton/metabolism ; Seawater/*chemistry ; Sulfur/analysis ; Sulfur Isotopes ; }, abstract = {Oxygenation of the Earth's surface is increasingly thought to have occurred in two steps. The first step, which occurred approximately 2,300 million years (Myr) ago, involved a significant increase in atmospheric oxygen concentrations and oxygenation of the surface ocean. A further increase in atmospheric oxygen appears to have taken place during the late Neoproterozoic period (approximately 800-542 Myr ago). This increase may have stimulated the evolution of macroscopic multicellular animals and the subsequent radiation of calcified invertebrates, and may have led to oxygenation of the deep ocean. However, the nature and timing of Neoproterozoic oxidation remain uncertain. Here we present high-resolution carbon isotope and sulphur isotope records from the Huqf Supergroup, Sultanate of Oman, that cover most of the Ediacaran period (approximately 635 to approximately 548 Myr ago). These records indicate that the ocean became increasingly oxygenated after the end of the Marinoan glaciation, and they allow us to identify three distinct stages of oxidation. When considered in the context of other records from this period, our data indicate that certain groups of eukaryotic organisms appeared and diversified during the second and third stages of oxygenation. The second stage corresponds with the Shuram excursion in the carbon isotope record and seems to have involved the oxidation of a large reservoir of organic carbon suspended in the deep ocean, indicating that this event may have had a key role in the evolution of eukaryotic organisms. Our data thus provide new insights into the oxygenation of the Ediacaran ocean and the stepwise restructuring of the carbon and sulphur cycles that occurred during this significant period of Earth's history.}, } @article {pmid17150103, year = {2006}, author = {Singiser, RH and McCann, RO}, title = {Evidence that talin alternative splice variants from Ciona intestinalis have different roles in cell adhesion.}, journal = {BMC cell biology}, volume = {7}, number = {}, pages = {40}, pmid = {17150103}, issn = {1471-2121}, support = {P20 RR020171/RR/NCRR NIH HHS/United States ; P20RR20171/RR/NCRR NIH HHS/United States ; }, mesh = {Actins/metabolism ; Alternative Splicing/physiology ; Amino Acid Sequence ; Animals ; Cell Adhesion/*physiology ; Ciona intestinalis/*physiology ; Cloning, Molecular ; HeLa Cells ; Humans ; Molecular Sequence Data ; Phylogeny ; Protein Binding ; Protein Isoforms/genetics/metabolism/physiology ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid ; Talin/genetics/*metabolism/*physiology ; Tissue Distribution ; Transfection ; }, abstract = {BACKGROUND: Talins are large, modular cytoskeletal proteins found in animals and amoebozoans such as Dictyostelium discoideum. Since the identification of a second talin gene in vertebrates, it has become increasingly clear that vertebrate Talin1 and Talin2 have non-redundant roles as essential links between integrins and the actin cytoskeleton in distinct plasma membrane-associated adhesion complexes. The conserved C-terminal I/LWEQ module is important for talin function. This structural element mediates the interaction of talins with F-actin. The I/LWEQ module also targets mammalian Talin1 to focal adhesion complexes, which are dynamic multicomponent assemblies required for cell adhesion and cell motility. Although Talin1 is essential for focal adhesion function, Talin2 is not targeted to focal adhesions. The nonvertebrate chordate Ciona intestinalis has only one talin gene, but alternative splicing of the talin mRNA produces two proteins with different C-terminal I/LWEQ modules. Thus, C. intestinalis contains two talins, Talin-a and Talin-b, with potentially different activities, despite having only one talin gene.

RESULTS: We show here that, based on their distribution in cDNA libraries, Talin-a and Talin-b are differentially expressed during C. intestinalis development. The I/LWEQ modules of the two proteins also have different affinities for F-actin. Consistent with the hypothesis that Talin-a and Talin-b have different roles in cell adhesion, the distinct I/LWEQ modules of Talin-a and Talin-b possess different subcellular targeting determinants. The I/LWEQ module of Talin-a is targeted to focal adhesions, where it most likely serves as the link between integrin and the actin cytoskeleton. The Talin-b I/LWEQ module is not targeted to focal adhesions, but instead preferentially labels F-actin stress fibers. These different properties of C. intestinalis the Talin-a and Talin-b I/LWEQ modules mimic the differences between mammalian Talin1 and Talin2.

CONCLUSION: Vertebrates and D. discoideum contain two talin genes that encode proteins with different functions. The urochordate C. intestinalis has a single talin gene but produces two separate talins by alternative splicing that vary in a domain crucial for talin function. This suggests that multicellular organisms require multiple talins as components of adhesion complexes. In C. intestinalis, alternative splicing, rather than gene duplication followed by neo-functionalization, accounts for the presence of multiple talins with different properties. Given that C. intestinalis is an excellent model system for chordate biology, the study of Talin-a and Talin-b will lead to a deeper understanding of cell adhesion in the chordate lineage and how talin functions have been parceled out to multiple proteins during metazoan evolution.}, } @article {pmid17148551, year = {2007}, author = {Smolenaars, MM and Madsen, O and Rodenburg, KW and Van der Horst, DJ}, title = {Molecular diversity and evolution of the large lipid transfer protein superfamily.}, journal = {Journal of lipid research}, volume = {48}, number = {3}, pages = {489-502}, doi = {10.1194/jlr.R600028-JLR200}, pmid = {17148551}, issn = {0022-2275}, mesh = {Animals ; Apolipoproteins B/chemistry/genetics/metabolism ; Carrier Proteins/chemistry/*genetics/*metabolism ; *Evolution, Molecular ; Humans ; Models, Molecular ; Phylogeny ; Protein Structure, Secondary ; Vitellogenins/chemistry/metabolism/physiology ; }, abstract = {Circulatory lipid transport in animals is mediated to a substantial extent by members of the large lipid transfer (LLT) protein (LLTP) superfamily. These proteins, including apolipoprotein B (apoB), bind lipids and constitute the structural basis for the assembly of lipoproteins. The current analyses of sequence data indicate that LLTPs are unique to animals and that these lipid binding proteins evolved in the earliest multicellular animals. In addition, two novel LLTPs were recognized in insects. Structural and phylogenetic analyses reveal three major families of LLTPs: the apoB-like LLTPs, the vitellogenin-like LLTPs, and the microsomal triglyceride transfer protein (MTP)-like LLTPs, or MTPs. The latter are ubiquitous, whereas the two other families are distributed differentially between animal groups. Besides similarities, remarkable variations are also found among LLTPs in their major lipid-binding sites (i.e., the LLT module as well as the predicted clusters of amphipathic secondary structure): variations such as protein modification and number, size, or occurrence of the clusters. Strikingly, comparative research has also highlighted a multitude of functions for LLTPs in addition to circulatory lipid transport. The integration of LLTP structure, function, and evolution reveals multiple adaptations, which have come about in part upon neofunctionalization of duplicated genes. Moreover, the change, exchange, and expansion of functions illustrate the opportune application of lipid-binding proteins in nature. Accordingly, comparative research exposes the structural and functional adaptations in animal lipid carriers and brings up novel possibilities for the manipulation of lipid transport.}, } @article {pmid17143289, year = {2006}, author = {Guder, C and Philipp, I and Lengfeld, T and Watanabe, H and Hobmayer, B and Holstein, TW}, title = {The Wnt code: cnidarians signal the way.}, journal = {Oncogene}, volume = {25}, number = {57}, pages = {7450-7460}, doi = {10.1038/sj.onc.1210052}, pmid = {17143289}, issn = {0950-9232}, mesh = {Animals ; Body Patterning ; Cnidaria ; Evolution, Molecular ; Hydra ; Ligands ; Models, Biological ; Phylogeny ; Sea Anemones ; Signal Transduction ; Wnt Proteins/metabolism/*physiology ; beta Catenin/metabolism ; }, abstract = {Cnidarians are the simplest metazoans with a nervous system. They are well known for their regeneration capacity, which is based on the restoration of a signalling centre (organizer). Recent work has identified the canonical Wnt pathway in the freshwater polyp Hydra, where it acts in organizer formation and regeneration. Wnt signalling is also essential for cnidarian embryogenesis. In the sea anemone Nematostella vectensis 11 of the 12 known wnt gene subfamilies were identified. Different wnt genes exhibit serial and overlapping expression domains along the oral-aboral axis of the embryo (the 'wnt code'). This is reminiscent of the hox code (cluster) in bilaterian embryogenesis that is, however, absent in cnidarians. It is proposed that the common ancestor of cnidarians and bilaterians invented a set of wnt genes that patterned the ancient main body axis. Major antagonists of Wnt ligands (e.g. Dkk 1/2/4) that were previously known only from chordates, are also present in cnidarians and exhibit a similar conserved function. The unexpectedly high level of genetic complexity of wnt genes evolved in early multi-cellular animals about 650 Myr ago and suggests a radical expansion of the genetic repertoire, concurrent with the evolution of multi-cellularity and the diversification of eumetazoan body plans.}, } @article {pmid17141969, year = {2007}, author = {Kurbel, S}, title = {Do high incidences of common neoplasms depend on evolutionary abandoned regulatory loops revived in tumor cells by mutations?.}, journal = {Medical hypotheses}, volume = {68}, number = {5}, pages = {991-994}, doi = {10.1016/j.mehy.2006.09.060}, pmid = {17141969}, issn = {0306-9877}, mesh = {Cell Transformation, Neoplastic ; *Evolution, Molecular ; Gene Expression Regulation, Neoplastic ; *Incidence ; *Models, Biological ; *Mutation ; Neoplasms/*epidemiology/*genetics/pathology ; }, abstract = {Neoplasms seem much more common than one might expect, considering complexity of the required cell malfunctions. It seems very unlikely to get them all set in the single cell by pure chance. Here presented idea is neoplasms exploit evolutionary abandoned regulatory mechanisms still contained in our genome. During evolution numerous changes have occurred in cell biology of multicellular organisms. Regulatory mechanisms developed, modified its affinity, sensitivity, and effects on different cells. Some eventually disappeared. Others got another chance to get involved in something different. Most of these changes are forever lost, but, inevitably, our genome contains codes for proteins that still can serve abandoned regulatory mechanisms that are not active in normal cells. Transformation from normal to malignant cells depends on accumulated alterations that remain compatible with cell survival and this can happen if alterations critical for cell survival activate old regulatory loops, obsolete in normal cells. Otherwise, mutated cells would die before becoming malignant. Based on this concept of ever-changing cellular function within survival limited borders, living cells can be considered confined in a well-defined time-space continuum that incorporate occurrence and disappearance of macromolecules, metabolites, mediators and physical influences. Numerous scenarios involving the same set of regulatory proteins emerged during evolution. All survival compatible scenarios were passed to next generations and many times retested. Evolutionary conservation of important proteins saved also all existing possibilities of interactions between them, so parts of abandoned scenarios can be activated in malignant cells. This box of forgotten tools in our genome might be the prerequisite of high incidences reported for common neoplasms.}, } @article {pmid17120023, year = {2007}, author = {Mani-Telang, P and Arnosti, DN}, title = {Developmental expression and phylogenetic conservation of alternatively spliced forms of the C-terminal binding protein corepressor.}, journal = {Development genes and evolution}, volume = {217}, number = {2}, pages = {127-135}, pmid = {17120023}, issn = {0949-944X}, support = {R01 GM056976/GM/NIGMS NIH HHS/United States ; GM56976/GM/NIGMS NIH HHS/United States ; }, mesh = {Alcohol Oxidoreductases/*genetics ; *Alternative Splicing ; Amino Acid Sequence ; Animals ; Base Sequence ; Coleoptera/genetics/growth & development ; Conserved Sequence ; DNA/genetics ; DNA-Binding Proteins/*genetics ; Diptera/genetics/growth & development ; Drosophila/genetics/growth & development ; Drosophila Proteins/genetics ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Genes, Insect ; Insect Proteins/*genetics ; Insecta/*genetics/*growth & development ; Molecular Sequence Data ; Phylogeny ; Protein Isoforms/genetics ; Repressor Proteins/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {The C-terminal binding protein (CtBP) is an evolutionarily conserved transcriptional corepressor found in multicellular eukaryotes. Multiple forms of the protein are typically found in animal cells, produced from separate genes and by alternative splicing. CtBP isoforms have also been implicated in cytoplasmic functions, including Golgi fission and vesicular trafficking. All forms of CtBP contain a conserved core domain that is homologous to alpha-hydroxyacid dehydrogenases, and a subset of isoforms (CtBP(L)) contain extensions at the C terminus. Despite distinct developmental profiles and knockout phenotypes in the mouse, the properties of different isoforms of the protein are found to be similar in many transcriptional assays. We have investigated the expression and conservation of distinct isoforms of the CtBP protein in insects and found that the expression of multiple, developmentally regulated isoforms is widely conserved. In a variety of Drosophila species, the relative abundance of CtBP(L) to CtBP(S) drops sharply after embryogenesis, revealing a conserved developmental shift. Despite the overall lower levels of this isoform, bioinformatic analysis reveals that exons encoding the C-terminal extension in CtBP(L) are conserved from Diptera to Coleoptera, suggesting that the CtBP(L) isoform contributes an important, evolutionarily conserved function.}, } @article {pmid17100098, year = {2006}, author = {Kutmin, AI}, title = {[Genomic imprinting: a case of inherited hematocrit, radiosensitivity, and antioxidant status in human being, as well as weight of newborn mammals].}, journal = {Zhurnal obshchei biologii}, volume = {67}, number = {5}, pages = {361-375}, pmid = {17100098}, issn = {0044-4596}, mesh = {Animals ; Antioxidants/*metabolism ; Birth Weight/*genetics ; *Genomic Imprinting ; Hematocrit ; Humans ; *Models, Genetic ; Radiation Tolerance/*genetics ; }, abstract = {Epigenetic hypothesis of dynamic genomic parental imprinting, explaining the mechanisms of formation and inheritance of quantitative characters in multicellular organisms, is proposed. Method for analyzing the compliance of quantitative characters of organisms with the hypothesis of dynamic genomic parental imprinting is developed. Examples of human characters and characters of other mammals inherited in accordance with the proposed model are given. It is concluded that the hypothesis can be used for studying ontogeny and explaining the mechanisms of inheritance of the morphoses providing the stability and evolution of species. Possible ways of further experimental verification of the hypothesis and areas of its practical application are discussed.}, } @article {pmid17089785, year = {2006}, author = {Semler, EJ and Ranucci, CS and Moghe, PV}, title = {Tissue assembly guided via substrate biophysics: applications to hepatocellular engineering.}, journal = {Advances in biochemical engineering/biotechnology}, volume = {102}, number = {}, pages = {1-46}, doi = {10.1007/10_012}, pmid = {17089785}, issn = {0724-6145}, support = {EB000922-01/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; Biocompatible Materials ; Biophysical Phenomena ; Biophysics ; Hepatocytes/cytology/drug effects/*physiology ; Humans ; Liver/cytology/drug effects/*growth & development ; Morphogenesis/drug effects/*physiology ; *Organ Culture Techniques ; Tissue Engineering/*methods ; }, abstract = {The biophysical nature of the cellular microenvironment, in combination with its biochemical properties, can critically modulate the outcome of three-dimensional (3-D) multicellular morphogenesis. This phenomenon is particularly relevant for the design of materials suitable for supporting hepatocellular cultures, where cellular morphology is known to be intimately linked to the functional output of the cells. This review summarizes recent work describing biophysical regulation of hepatocellular morphogenesis and function and focuses on the manner by which biochemical cues can concomitantly augment this responsiveness. In particular, two distinct design parameters of the substrate biophysics are examined--microtopography and mechanical compliance. Substrate microtopography, introduced in the form of increasing pore size on collagen sponges and poly(glycolic acid) (PGLA) foams, was demonstrated to restrict the evolution of cellular morphogenesis to two dimensions (subcellular and cellular void sizes) or induce 3-D cellular assembly (supercellular void size). These patterns of morphogenesis were additionally governed by the biochemical nature of the substrate and were highly correlated to resultant levels of cell function. Substrate mechanical compliance, introduced via increased chemical crosslinking of the basement membrane, Matrigel, and polyacrylamide gel substrates, also was shown to be able to induce active two-dimensional (2-D, rigid substrates) or 3-D (malleable substrates) cellular reorganization. The extent of morphogenesis and the ensuing levels of cell function were highly dependent on the biochemical nature of the cellular microenvironment, including the presence of increasing extracellular matrix (ECM) ligand and growth-factor concentrations. Collectively, these studies highlight not only the ability of substrate biophysics to control hepatocellular morphogenesis but also the ability of biochemical cues to further enhance these effects. In particular, results of these studies reveal novel means by which hepatocellular morphogenesis and assembly can be rationally manipulated leading to the strategic control of the expression of liver-specific functions for hepatic tissue-engineering applications.}, } @article {pmid17083004, year = {2007}, author = {Gatenby, RA and Frieden, BR}, title = {Information theory in living systems, methods, applications, and challenges.}, journal = {Bulletin of mathematical biology}, volume = {69}, number = {2}, pages = {635-657}, doi = {10.1007/s11538-006-9141-5}, pmid = {17083004}, issn = {0092-8240}, mesh = {Computational Biology/*methods ; Developmental Biology ; *Information Theory ; *Models, Biological ; }, abstract = {Living systems are distinguished in nature by their ability to maintain stable, ordered states far from equilibrium. This is despite constant buffeting by thermodynamic forces that, if unopposed, will inevitably increase disorder. Cells maintain a steep transmembrane entropy gradient by continuous application of information that permits cellular components to carry out highly specific tasks that import energy and export entropy. Thus, the study of information storage, flow and utilization is critical for understanding first principles that govern the dynamics of life. Initial biological applications of information theory (IT) used Shannon's methods to measure the information content in strings of monomers such as genes, RNA, and proteins. Recent work has used bioinformatic and dynamical systems to provide remarkable insights into the topology and dynamics of intracellular information networks. Novel applications of Fisher-, Shannon-, and Kullback-Leibler informations are promoting increased understanding of the mechanisms by which genetic information is converted to work and order. Insights into evolution may be gained by analysis of the the fitness contributions from specific segments of genetic information as well as the optimization process in which the fitness are constrained by the substrate cost for its storage and utilization. Recent IT applications have recognized the possible role of nontraditional information storage structures including lipids and ion gradients as well as information transmission by molecular flux across cell membranes. Many fascinating challenges remain, including defining the intercellular information dynamics of multicellular organisms and the role of disordered information storage and flow in disease.}, } @article {pmid17073552, year = {2006}, author = {Sun, Y and Li, H and Yang, H and Rao, MS and Zhan, M}, title = {Mechanisms controlling embryonic stem cell self-renewal and differentiation.}, journal = {Critical reviews in eukaryotic gene expression}, volume = {16}, number = {3}, pages = {211-231}, doi = {10.1615/critreveukargeneexpr.v16.i3.20}, pmid = {17073552}, issn = {1045-4403}, support = {//Intramural NIH HHS/United States ; }, mesh = {Animals ; *Cell Differentiation ; Embryonic Stem Cells/*cytology/*physiology ; Gene Expression Regulation, Developmental ; Humans ; Pluripotent Stem Cells/*cytology/*physiology ; Signal Transduction ; Transcription Factors/physiology ; }, abstract = {Embryonic stem (ES) cells are pluripotent cells with indefinite replication potential and ability to differentiate into all types of cells. An understanding of the regulatory mechanisms responsible for pluripotency in ES cells is critical for realizing their potential in regenerative medicine and science. Cross-species studies on ES cells have identified pathways and networks that are either fundamental to or species-specific for self-renewal and differentiation. Although pluripotency as an essential function in multicellular organisms is conserved through evolution, mechanisms primed for differentiation contribute substantially to the differences among stem cells derived from different tissues or species. Transcriptome mapping analysis has determined the chromosomal domains of gene coexpression patterns specific to the ES state and demonstrated that regulation of ES cell development is operative at both the local chromosomal domain level and global level. Combinatorial signals from multiple pathways regulate the expression of key intrinsic factors critical for ES cell fate determination. The regulatory core formed by Oct4, Sox2, and Nanog, in particular, activates genes critical for self-renewal and represses genes initiating differentiation, controlling ES cell pluripotency. Here, we review recent findings on mechanisms controlling ES cell development. By integrating data from different sources, we present a global picture of how ES cells reach the decision of self-renewal or differentiation.}, } @article {pmid17070958, year = {2007}, author = {Ram, O and Ast, G}, title = {SR proteins: a foot on the exon before the transition from intron to exon definition.}, journal = {Trends in genetics : TIG}, volume = {23}, number = {1}, pages = {5-7}, doi = {10.1016/j.tig.2006.10.002}, pmid = {17070958}, issn = {0168-9525}, mesh = {Alternative Splicing/*genetics ; *Evolution, Molecular ; Introns/*genetics ; *Models, Genetic ; Nuclear Proteins/*genetics ; RNA-Binding Proteins/*genetics ; Schizosaccharomyces/*genetics ; Schizosaccharomyces pombe Proteins/*genetics ; Serine-Arginine Splicing Factors ; }, abstract = {Two recent publications illuminate the evolution of alternative splicing, showing that a SR (serine-arginine-rich) protein that regulates alternative splicing in multicellular organisms is also found in a unicellular organism without alternative splicing, in which it can assist in the splicing of weak introns. Moreover, insertion of SR proteins into an organism lacking such proteins can restore the splicing of weak introns. These results imply that SR proteins had already facilitated the splicing of weak introns before the evolution of alternative splicing.}, } @article {pmid17068665, year = {2006}, author = {Stelzner, F}, title = {[Autoregulatory growth control of adenomatous polyps and carcinogenesis in the colorectal region. Basics of tumor surgery Part I].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {77}, number = {11}, pages = {1048-1055}, pmid = {17068665}, issn = {0009-4722}, mesh = {Adenomatous Polyposis Coli/genetics/pathology/surgery ; Adenomatous Polyps/genetics/*pathology/surgery ; Bone Marrow Cells/pathology ; Cell Division/genetics/*physiology ; Cell Transformation, Neoplastic/genetics/pathology ; Chromosome Aberrations ; Colon/pathology/surgery ; Colonic Polyps/genetics/*pathology/*surgery ; Colorectal Neoplasms/genetics/*pathology/*surgery ; Gene Expression Regulation, Neoplastic/physiology ; Homeostasis/genetics/*physiology ; Humans ; Neoplasm Staging ; Prognosis ; Rectum/pathology/surgery ; }, abstract = {Autoregulatory growth control of adenomatous polyps in the colon and rectum is an important factor in the success of sphincter-sparing surgical resections. It is the basis for the coexistence of billions of somatic cells in multicellular organisms. Similar to normal mucosa, adenomatous polyps in the colorectum show autoregulatory growth control in their tissues. This applies whether they are differentiated or undifferentiated. In most cases, their growth and expansion is controlled throughout life. While colorectal adenomas have malignant potential, their transformation to cancerous lesions is exceedingly rare (e.g., in familial polyposis, or FAP, with a prevalence of only one in 10,000). It has been hypothesized that "fully developed adenomas" frequently are a prestage of colorectal cancer. However, convincing evidence on a molecular level that this so-called adenoma-carcinoma sequence indeed occurs in vivo is lacking. In contrast, there is good evidence that colorectal carcinogenesis is a microevolutionary process and that the irrevocable loss of autoregulatory growth control is one of its features. The most prominent homing area for colorectal cancer is the rectum. If the rectum is resected, metachronous cancer occurs only very rarely. The most distal quarter of the rectum is cloacal in origin and a pivotal structure for anorectal continence. It should be preserved whenever a more proximal location of the tumor makes this possible. These conclusions are based on our extensive case series and observations extending over several decades.}, } @article {pmid17068267, year = {2006}, author = {Schaap, P and Winckler, T and Nelson, M and Alvarez-Curto, E and Elgie, B and Hagiwara, H and Cavender, J and Milano-Curto, A and Rozen, DE and Dingermann, T and Mutzel, R and Baldauf, SL}, title = {Molecular phylogeny and evolution of morphology in the social amoebas.}, journal = {Science (New York, N.Y.)}, volume = {314}, number = {5799}, pages = {661-663}, pmid = {17068267}, issn = {1095-9203}, support = {076618/WT_/Wellcome Trust/United Kingdom ; BB/D013453/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; COD16760/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 057137/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Biological Evolution ; DNA, Protozoan/genetics ; DNA, Ribosomal/genetics ; Dictyosteliida/*classification/*cytology/genetics/growth & development ; Dictyostelium/classification/cytology/genetics/growth & development ; Genes, Protozoan ; Molecular Sequence Data ; *Phylogeny ; RNA, Ribosomal/genetics ; Spores, Protozoan/cytology ; Tubulin/genetics ; }, abstract = {The social amoebas (Dictyostelia) display conditional multicellularity in a wide variety of forms. Despite widespread interest in Dictyostelium discoideum as a model system, almost no molecular data exist from the rest of the group. We constructed the first molecular phylogeny of the Dictyostelia with parallel small subunit ribosomal RNA and a-tubulin data sets, and we found that dictyostelid taxonomy requires complete revision. A mapping of characters onto the phylogeny shows that the dominant trend in dictyostelid evolution is increased size and cell type specialization of fruiting structures, with some complex morphologies evolving several times independently. Thus, the latter may be controlled by only a few genes, making their underlying mechanisms relatively easy to unravel.}, } @article {pmid17067006, year = {2006}, author = {Bartels, PH and Ranger-Moore, J and Alberts, D and Hess, L and Scarpelli, M and Montironi, R}, title = {Carcinogenesis and the hypothesis of phylogenetic reversion.}, journal = {Analytical and quantitative cytology and histology}, volume = {28}, number = {5}, pages = {243-252}, pmid = {17067006}, support = {P01 CA27502/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Transformation, Neoplastic/*genetics/*pathology ; Disease Progression ; Health ; Humans ; *Models, Genetic ; Neoplasms/*genetics/metabolism/*pathology ; Phylogeny ; }, abstract = {Chemoprevention must target early molecular events involved in malignant transformation. The sequence of events leading from a normally functioning interphase cell to an uncontrolled tumor cell is only partially understood, impeding systematic design of chemopreventive agents. The respective roles of mutagenic and epigenetic mechanisms have not been definitively established. Also, traditional models do not appear to incorporate cellular response to events leading to carcinogenesis. A perspective on system response offered by complexity science elucidates the roles of feedback and control in maintaining functional stability during carcinogenesis. Carcinogenesis is seen as a process of epigenetic redifferentiation resulting in a cell behaving like an archetypal karyocyte free of growth restraints (phylogenetic reversion). Genes that evolved during the development of multicellular organisms, restraining uncontrolled growth and regulating intercell communication may be systematically silenced during carcinogenesis. The formation of heterochromatin, which results in epigenetic silencing by hypermethylation in CpG-dense islands, finds expression in the nuclear chromatin pattern. Karyometry is an integrating biomarker of chromatin pattern information that accommodates the possibility of multiple, differently ordered pathways and provides exquisite sensitivity, allowing detection of very early transformation events. Its use can monitor the impact of chemopreventive agents on the earliest events in progression to cancer.}, } @article {pmid17055697, year = {2007}, author = {Sun, Y and Li, H and Liu, Y and Shin, S and Mattson, MP and Rao, MS and Zhan, M}, title = {Cross-species transcriptional profiles establish a functional portrait of embryonic stem cells.}, journal = {Genomics}, volume = {89}, number = {1}, pages = {22-35}, pmid = {17055697}, issn = {0888-7543}, support = {Z01 AG000619-01//Intramural NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/genetics ; Cell Line ; Embryonic Stem Cells/cytology/*metabolism ; Gene Expression Profiling ; Growth Substances/genetics ; Humans ; Mice ; Pluripotent Stem Cells/cytology/metabolism ; Signal Transduction/genetics ; Species Specificity ; Transcription Factors/genetics ; *Transcription, Genetic ; }, abstract = {An understanding of the regulatory mechanisms responsible for pluripotency in embryonic stem cells (ESCs) is critical for realizing their potential in medicine and science. Significant similarities exist among ESCs harvested from different species, yet major differences have also been observed. Here, by cross-species analysis of a large set of functional categories and all transcription factors and growth factors, we reveal conserved and divergent functional landscapes underlining fundamental and species-specific mechanisms that regulate ESC development. Global transcriptional trends derived from all expressed genes, instead of differentially expressed genes alone, were examined, allowing for a higher discriminating power in the functional portrait. We demonstrate that cross-species correlation of transcriptional changes that occur upon ESC differentiation is a powerful predictor of ESC-important biological pathways and functional cores within a pathway. Hundreds of functional modules, as defined by Gene Ontology, were associated with conserved expression patterns but bear no overt relationship to ESC development, suggestive of new mechanisms critical to ESC pluripotency. Yet other functional modules were not conserved; instead, they were significantly up-regulated in ESCs of either species, suggestive of species-specific regulation. The comparisons of ESCs across species and between human ESCs and embryonal carcinoma stem cells suggest that while pluripotency as an essential function in multicellular organisms is conserved throughout evolution, mechanisms primed for differentiation are less conserved and contribute substantially to the differences among stem cells derived from different tissues or species. Our findings establish a basis for defining the "stemness" properties of ESCs from the perspective of functional conservation and variation. The data and analyses resulting from this study provide a framework for new hypotheses and research directions and a public resource for functional genomics of ESCs.}, } @article {pmid17041880, year = {2006}, author = {Rudall, PJ}, title = {How many nuclei make an embryo sac in flowering plants?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {28}, number = {11}, pages = {1067-1071}, doi = {10.1002/bies.20488}, pmid = {17041880}, issn = {0265-9247}, mesh = {Cell Nucleus/genetics/*physiology ; Cell Proliferation ; Flowers/*cytology/*embryology/genetics ; *Plant Cells ; Plants/*embryology/genetics ; Time Factors ; }, abstract = {Research on early-divergent angiosperms, including Amborella, the putative sister to all other extant angiosperms, is increasingly used as a yardstick to infer the nature of the hypothetical ancestral angiosperm. Some traits are relatively diverse (and hence relatively labile) in this phylogenetic grade, compared with the more derived eudicot clade, in which developmental patterns have become increasingly canalized. One of the many mysteries surrounding the origin of the angiosperms is the evolutionary origin of the Polygonum-type embryo sac (monosporic, eight-nucleate and seven-celled) that occurs in the majority of flowering plants. Observations on the megagametophyte of Amborella are conflicting, but a recent report of a supernumerary synergid in this genus raises the question of whether the Polygonum-type embryo sac is derived by duplication of a four-nucleate structure or by reduction from a multicellular structure.}, } @article {pmid17036001, year = {2006}, author = {Goldblatt, C and Lenton, TM and Watson, AJ}, title = {Bistability of atmospheric oxygen and the Great Oxidation.}, journal = {Nature}, volume = {443}, number = {7112}, pages = {683-686}, doi = {10.1038/nature05169}, pmid = {17036001}, issn = {1476-4687}, mesh = {Atmosphere/*chemistry ; Biological Evolution ; Carbon/metabolism ; History, Ancient ; Methane/metabolism ; Oxidation-Reduction ; Oxygen/analysis/*chemistry/*metabolism ; Ozone/metabolism ; Photosynthesis ; Time Factors ; Ultraviolet Rays ; }, abstract = {The history of the Earth has been characterized by a series of major transitions separated by long periods of relative stability. The largest chemical transition was the 'Great Oxidation', approximately 2.4 billion years ago, when atmospheric oxygen concentrations rose from less than 10(-5) of the present atmospheric level (PAL) to more than 0.01 PAL, and possibly to more than 0.1 PAL. This transition took place long after oxygenic photosynthesis is thought to have evolved, but the causes of this delay and of the Great Oxidation itself remain uncertain. Here we show that the origin of oxygenic photosynthesis gave rise to two simultaneously stable steady states for atmospheric oxygen. The existence of a low-oxygen (less than 10(-5) PAL) steady state explains how a reducing atmosphere persisted for at least 300 million years after the onset of oxygenic photosynthesis. The Great Oxidation can be understood as a switch to the high-oxygen (more than 5 x 10(-3) PAL) steady state. The bistability arises because ultraviolet shielding of the troposphere by ozone becomes effective once oxygen levels exceed 10(-5) PAL, causing a nonlinear increase in the lifetime of atmospheric oxygen. Our results indicate that the existence of oxygenic photosynthesis is not a sufficient condition for either an oxygen-rich atmosphere or the presence of an ozone layer, which has implications for detecting life on other planets using atmospheric analysis and for the evolution of multicellular life.}, } @article {pmid17033814, year = {2007}, author = {Lan, DZ and Pollard, AE and Knisley, SB and Fast, VG}, title = {Optical mapping of V(m) and Ca(i)(2+) in a model of arrhythmias induced by local catecholamine application in patterned cell cultures.}, journal = {Pflugers Archiv : European journal of physiology}, volume = {453}, number = {6}, pages = {871-877}, pmid = {17033814}, issn = {0031-6768}, support = {R01 HL092049/HL/NHLBI NIH HHS/United States ; HL67728/HL/NHLBI NIH HHS/United States ; HL67748/HL/NHLBI NIH HHS/United States ; HL67961/HL/NHLBI NIH HHS/United States ; }, mesh = {Aniline Compounds ; Animals ; Arrhythmias, Cardiac/chemically induced/*metabolism ; Calcium/metabolism ; Calcium Signaling/drug effects/*physiology ; Cell Culture Techniques ; Cells, Cultured ; Epinephrine/*pharmacology ; Fluorescent Dyes ; Myocytes, Cardiac/cytology/drug effects/*physiology ; Rats ; Rats, Wistar ; Signal Processing, Computer-Assisted ; Sympathomimetics/*pharmacology ; Xanthenes ; }, abstract = {Catecholamines are known to provoke cardiac arrhythmias, but important aspects such as localization of the arrhythmia source in multicellular tissue and exact ionic mechanisms are not well-known. In this work, a multicellular model of arrhythmias caused by local epinephrine application was developed; V (m) and Ca(i)(2+) changes at the arrhythmia source were measured using fluorescent dyes and high-resolution optical mapping. Cultured strands of neonatal rat myocytes (width approximately 0.4 mm) were produced by patterned growth. Epinephrine (1 micromol/l) was applied over an area of 0.3-0.6 mm via two micropipettes, and strands were stimulated by burst pacing. Local epinephrine application caused triggered arrhythmias with cycle lengths of 202-379 ms and duration of >10 s in 9 out of 16 preparations. Optical V(m) mapping demonstrated that in 78% of cases, the source of arrhythmia was located at the boundary of the locally perfused area. Staining with Ca(i)(2+)-sensitive dye Fluo-4 prevented arrhythmia induction in most cases (85%) likely due to Ca(2+) buffering by the dye. Optical Ca(i)(2+) mapping revealed non-propagated Ca(i)(2+) oscillations at the boundary of the locally perfused area in 45% cases. In conclusion, we developed a new model of catecholamine-dependent arrhythmias allowing mapping of V(m) and Ca(i)(2+) at the arrhythmia source with microscopic resolution. The arrhythmias typically originated from the boundary of the epinephrine-perfused area. The location of the arrhythmia source correlated with localized Ca(i)(2+) oscillations suggesting that arrhythmias were caused by Ca(i)(2+) overload at these locations.}, } @article {pmid17032475, year = {2007}, author = {Shao, R and Barker, SC}, title = {Mitochondrial genomes of parasitic arthropods: implications for studies of population genetics and evolution.}, journal = {Parasitology}, volume = {134}, number = {Pt 2}, pages = {153-167}, doi = {10.1017/S0031182006001429}, pmid = {17032475}, issn = {0031-1820}, mesh = {Animals ; Arthropods/classification/*genetics ; Base Sequence ; DNA, Mitochondrial/*genetics ; Evolution, Molecular ; Genetics, Population/methods ; *Genome ; Mitochondria/*genetics ; Phylogeny ; }, abstract = {Over 39000 species of arthropods parasitize humans, domestic animals and wildlife. Despite their medical, veterinary and economic importance, most aspects of the population genetics and evolution of the vast majority of parasitic arthropods are poorly understood. Mitochondrial genomes are a rich source of markers for studies of population genetics and evolution. These markers include (1) nucleotide sequences of each of the 37 mitochondrial genes and non-coding regions; (2) concatenated nucleotide sequences of 2 or more genes; and (3) genomic features, such as gene duplications, gene rearrangements, and changes in gene content and secondary structures of RNAs. To date, the mitochondrial genomes of over 700 species of multi-cellular animals have been sequenced entirely, however, only 24 of these species are parasitic arthropods. Of the mitochondrial genome markers, only the nucleotide sequences of 4 mitochondrial genes, cox1, cob, rrnS and rrnL, have been well explored in population genetic and evolutionary studies of parasitic arthropods whereas the sequences of the other 33 genes, and various genomic features have not. We review current knowledge of the mitochondrial genomes of parasitic arthropods, summarize applications of mitochondrial genes and genomic features in population genetic and evolutionary studies, and highlight prospects for future research.}, } @article {pmid17030541, year = {2007}, author = {Richardson, AO and Palmer, JD}, title = {Horizontal gene transfer in plants.}, journal = {Journal of experimental botany}, volume = {58}, number = {1}, pages = {1-9}, doi = {10.1093/jxb/erl148}, pmid = {17030541}, issn = {0022-0957}, support = {R01-GM-70612/GM/NIGMS NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; *Gene Transfer, Horizontal ; Genes, Mitochondrial ; Genes, Plant ; Magnoliopsida/*genetics ; Phylogeny ; Plants/*genetics ; Polymerase Chain Reaction ; }, abstract = {Horizontal gene transfer (HGT) has played a major role in bacterial evolution and is fairly common in certain unicellular eukaryotes. However, the prevalence and importance of HGT in the evolution of multicellular eukaryotes remain unclear. Recent studies indicate that plant mitochondrial genomes are unusually active in HGT relative to all other organellar and nuclear genomes of multicellular eukaryotes. Although little about the mechanisms of plant HGT is known, several studies have implicated parasitic plants as both donors and recipients of mitochondrial genes. Most cases uncovered thus far have involved a single transferred gene per species; however, recent work has uncovered a case of massive HGT in Amborella trichopoda involving acquisition of at least a few dozen and probably hundreds of foreign mitochondrial genes. These foreign genes came from multiple donors, primarily eudicots and mosses. This review will examine the implications of such massive transfer, the potential mechanisms and consequences of plant-to-plant mitochondrial HGT in general, as well as the limited evidence for HGT in plant chloroplast and nuclear genomes.}, } @article {pmid17029626, year = {2006}, author = {Freilich, S and Massingham, T and Blanc, E and Goldovsky, L and Thornton, JM}, title = {Relating tissue specialization to the differentiation of expression of singleton and duplicate mouse proteins.}, journal = {Genome biology}, volume = {7}, number = {10}, pages = {R89}, pmid = {17029626}, issn = {1474-760X}, support = {GRO66750MA//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Differentiation ; *Evolution, Molecular ; *Gene Duplication ; *Gene Expression Regulation ; Genes, Duplicate ; Kinetics ; Mice ; Proteins/*genetics ; Sequence Homology, Amino Acid ; Species Specificity ; }, abstract = {BACKGROUND: Gene duplications have been hypothesized to be a major factor in enabling the evolution of tissue differentiation. Analyses of the expression profiles of duplicate genes in mammalian tissues have indicated that, with time, the expression patterns of duplicate genes diverge and become more tissue specific. We explored the relationship between duplication events, the time at which they took place, and both the expression breadth of the duplicated genes and the cumulative expression breadth of the gene family to which they belong.

RESULTS: We show that only duplicates that arose through post-multicellularity duplication events show a tendency to become more specifically expressed, whereas such a tendency is not observed for duplicates that arose in a unicellular ancestor. Unlike the narrow expression profile of the duplicated genes, the overall expression of gene families tends to maintain a global expression pattern.

CONCLUSION: The work presented here supports the view suggested by the subfunctionalization model, namely that expression divergence in different tissues, following gene duplication, promotes the retention of a gene in the genome of multicellular species. The global expression profile of the gene families suggests division of expression between family members, whose expression becomes specialized. Because specialization of expression is coupled with an increased rate of sequence divergence, it can facilitate the evolution of new, tissue-specific functions.}, } @article {pmid17028206, year = {2006}, author = {Fukada, K and Inoue, T and Shiraishi, H}, title = {A posttranslationally regulated protease, VheA, is involved in the liberation of juveniles from parental spheroids in Volvox carteri.}, journal = {The Plant cell}, volume = {18}, number = {10}, pages = {2554-2566}, pmid = {17028206}, issn = {1040-4651}, mesh = {Amino Acid Sequence ; Base Sequence ; Cations, Divalent ; Cloning, Molecular ; DNA Primers ; DNA, Complementary ; Genes, Plant ; Hydrogen-Ion Concentration ; Molecular Sequence Data ; Peptide Hydrolases/chemistry/genetics/isolation & purification/*metabolism ; *Protein Processing, Post-Translational ; RNA, Messenger/genetics/metabolism ; Sequence Homology, Amino Acid ; Volvox/*enzymology/genetics ; }, abstract = {The lineage of volvocine algae includes unicellular Chlamydomonas and multicellular Volvox in addition to their colonial relatives intermediate in size and cell number. In an asexual life cycle, daughter cells of Chlamydomonas hatch from parental cell walls soon after cell division, while Volvox juveniles are released from parental spheroids after the completion of various developmental events required for the survival of multicellular juveniles. Thus, heterochronic change in the timing of hatching is considered to have played an important role in the evolution of multicellularity in volvocine algae. To study the hatching process in Volvox carteri, we purified a 125-kD Volvox hatching enzyme (VheA) from a culture medium with enzymatic activity to degrade the parental spheroids. The coding region of vheA contains a prodomain with a transmembrane segment, a subtilisin-like Ser protease domain, and a functionally unknown domain, although purified 125-kD VheA does not contain a prodomain. While 143-kD VheA with a prodomain is synthesized long before the hatching stage, 125-kD VheA is released into the culture medium during hatching due to cleavage processing at the site between the prodomain and the subtilisin-like Ser protease domain, indicating that posttranslational regulation is involved in the determination of the timing of hatching.}, } @article {pmid17018168, year = {2006}, author = {Welburn, SC and Macleod, E and Figarella, K and Duzensko, M}, title = {Programmed cell death in African trypanosomes.}, journal = {Parasitology}, volume = {132 Suppl}, number = {}, pages = {S7-S18}, doi = {10.1017/S0031182006000825}, pmid = {17018168}, issn = {0031-1820}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Apoptosis/*physiology ; Host-Parasite Interactions/physiology ; Humans ; Insect Vectors/parasitology ; Life Cycle Stages/*physiology ; Oxidative Stress/physiology ; Parasitemia/parasitology ; Population Density ; Trypanosoma brucei brucei/*cytology/genetics/growth & development/*physiology ; Trypanosomiasis, African/parasitology ; Tsetse Flies/parasitology ; }, abstract = {Until recently it had generally been assumed that apoptosis and other forms of programmed cell death evolved during evolution of the metazoans to regulate growth and development in these multicellular organisms. However, recent research is adding strength to the original phenotypic observations described almost a decade ago which indicated that some parasitic protozoa may have evolved a cell death pathway analogous to the process described as apoptosis in metazoa. Here we explore the implications of a programmed cell death pathway in the African tsetse-transmitted trypanosomes.}, } @article {pmid17017062, year = {2006}, author = {Schwarzenbach, GA and Ward, PI}, title = {Responses to selection on phenoloxidase activity in yellow dung flies.}, journal = {Evolution; international journal of organic evolution}, volume = {60}, number = {8}, pages = {1612-1621}, pmid = {17017062}, issn = {0014-3820}, mesh = {Animals ; Catechol Oxidase/metabolism ; Diptera/*enzymology/genetics/*physiology ; Enzyme Activation ; Enzyme Precursors/metabolism ; Longevity ; Monophenol Monooxygenase/*genetics/*metabolism ; Reproduction/genetics/physiology ; *Selection, Genetic ; Sex Ratio ; }, abstract = {Maintaining an immune system is costly. Resource allocation to immunity should therefore trade off against other fitness components. Numerous studies have found phenotypic trade-offs after immune challenge, but few have investigated genetic correlations between immune components and other traits. Furthermore, empirical evidence for the costs of maintaining an innate immune system in the absence of challenges is rare. We examined responses to artificial selection on phenoloxidase (PO) activity, an important part of the insect innate defense against multicellular pathogens, in yellow dung flies, Scathophaga stercoraria (L.). After 15 generations of successful selection on PO activity, we measured reproductive characters: clutch size, egg hatching rates, adult emergence rates, and adult longevity. We found no evidence for negative genetic correlations between PO activity and reproduction. In fact, flies of lines selected for increased PO activity had larger first clutches, and flies of lines selected for decreased PO activity had smaller ones. However, flies from high-PO lines died earlier than did low-PO flies when no food was available; that is, there is a survival cost of running at high PO levels in the absence of challenge. Variation in resource acquisition or use may lead to positive genetic correlations between PO and fertility and fecundity. The negative correlation between PO and longevity under starvation may indicate that variation for resource acquisition is maintained by a cost of acquisition, based on a genotype-environment interaction.}, } @article {pmid17015832, year = {2006}, author = {Goldman, BS and Nierman, WC and Kaiser, D and Slater, SC and Durkin, AS and Eisen, JA and Ronning, CM and Barbazuk, WB and Blanchard, M and Field, C and Halling, C and Hinkle, G and Iartchuk, O and Kim, HS and Mackenzie, C and Madupu, R and Miller, N and Shvartsbeyn, A and Sullivan, SA and Vaudin, M and Wiegand, R and Kaplan, HB}, title = {Evolution of sensory complexity recorded in a myxobacterial genome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, number = {41}, pages = {15200-15205}, pmid = {17015832}, issn = {0027-8424}, support = {R37 GM023441/GM/NIGMS NIH HHS/United States ; GM23441/GM/NIGMS NIH HHS/United States ; }, mesh = {Deltaproteobacteria/genetics/physiology ; *Evolution, Molecular ; *Genome, Bacterial ; Molecular Sequence Data ; Multigene Family ; Myxococcus xanthus/*genetics/growth & development/physiology ; RNA, Ribosomal, 16S/genetics ; Signal Transduction/genetics/physiology ; }, abstract = {Myxobacteria are single-celled, but social, eubacterial predators. Upon starvation they build multicellular fruiting bodies using a developmental program that progressively changes the pattern of cell movement and the repertoire of genes expressed. Development terminates with spore differentiation and is coordinated by both diffusible and cell-bound signals. The growth and development of Myxococcus xanthus is regulated by the integration of multiple signals from outside the cells with physiological signals from within. A collection of M. xanthus cells behaves, in many respects, like a multicellular organism. For these reasons M. xanthus offers unparalleled access to a regulatory network that controls development and that organizes cell movement on surfaces. The genome of M. xanthus is large (9.14 Mb), considerably larger than the other sequenced delta-proteobacteria. We suggest that gene duplication and divergence were major contributors to genomic expansion from its progenitor. More than 1,500 duplications specific to the myxobacterial lineage were identified, representing >15% of the total genes. Genes were not duplicated at random; rather, genes for cell-cell signaling, small molecule sensing, and integrative transcription control were amplified selectively. Families of genes encoding the production of secondary metabolites are overrepresented in the genome but may have been received by horizontal gene transfer and are likely to be important for predation.}, } @article {pmid17014493, year = {2006}, author = {Curtis, PD and Geyer, R and White, DC and Shimkets, LJ}, title = {Novel lipids in Myxococcus xanthus and their role in chemotaxis.}, journal = {Environmental microbiology}, volume = {8}, number = {11}, pages = {1935-1949}, doi = {10.1111/j.1462-2920.2006.01073.x}, pmid = {17014493}, issn = {1462-2912}, mesh = {1-Acylglycerol-3-Phosphate O-Acyltransferase/chemistry/genetics ; Acetyltransferases/chemistry/genetics ; Aldehyde Oxidoreductases/chemistry/genetics ; Amino Acid Sequence ; Chemotaxis/*physiology ; Fatty Acids/biosynthesis/chemistry/*physiology ; Molecular Sequence Data ; Myxococcus xanthus/*chemistry/genetics/*physiology ; Phosphatidylethanolamines/chemistry/*physiology ; Sequence Alignment ; }, abstract = {Organisms that colonize solid surfaces, like Myxococcus xanthus, use novel signalling systems to organize multicellular behaviour. Phosphatidylethanolamine (PE) containing the fatty acid 16:1omega5 (Delta11) elicits a chemotactic response. The phenomenon was examined by observing the effects of PE species with varying fatty acid pairings. Wild-type M. xanthus contains 17 different PE species under vegetative conditions and 19 at the midpoint of development; 13 of the 17 have an unsaturated fatty acid at the sn-1 position, a novelty among Proteobacteria. Myxococcus xanthus has two glycerol-3-phosphate acyltransferase (PlsB) homologues which add the sn-1 fatty acid. Each produces PE with 16:1 at the sn-1 position and supports growth and fruiting body development. Deletion of plsB1 (MXAN3288) results in more dramatic changes in PE species distribution than deletion of plsB2 (MXAN1675). PlsB2 has a putative N-terminal eukaryotic fatty acid reductase domain and may support both ether lipid synthesis and PE synthesis. Disruption of a single sn-2 acyltransferase homologue (PlsC, of which M. xanthus contains five) results in minor changes in membrane PE. Derivatization of purified PE extracts with dimethyldisulfide was used to determine the position of the double bonds in unsaturated fatty acids. The results suggest that Delta5 and Delta11 desaturases may create the double bonds after synthesis of the fatty acid. Phosphatidylethanolamine enriched for 16:1 at the sn-1 position stimulates chemotaxis more strongly than PE with 16:1 enriched at the sn-2 position. It appears that the deployment of a rare fatty acid (16:1omega5) at an unusual position (sn-1) has facilitated the evolution of a novel cell signal.}, } @article {pmid17011141, year = {2006}, author = {Yoshida, K and Fujisawa, T and Hwang, JS and Ikeo, K and Gojobori, T}, title = {Degeneration after sexual differentiation in hydra and its relevance to the evolution of aging.}, journal = {Gene}, volume = {385}, number = {}, pages = {64-70}, doi = {10.1016/j.gene.2006.06.031}, pmid = {17011141}, issn = {0378-1119}, mesh = {Animals ; *Biological Evolution ; Female ; Hydra/*genetics/*growth & development/physiology ; Male ; Models, Genetic ; Reproduction ; Sex Differentiation/*genetics ; Species Specificity ; Time Factors ; }, abstract = {Aging occurs in most multicellular animals, yet some primitive animals do not show any sign of aging. This raises the following question: How have metazoans acquired the trait of aging in the course of evolution? Comparative studies of various species have provided a clue to this question by showing that sexually reproducing organisms predominantly undergo aging. The evolutionary theory "pleiotropy" also postulates aging as a price for facilitating the reproduction in the early life stage of an organism. For investigating the association between sexual reproduction and aging, a sexual phase-inducible organism in a laboratory would be suitable. One of such organisms is hydra, a genus of Cnidaria. Asexual hydra has been considered to be immortal, but there is the possibility that hydra undergoes aging after sexual reproduction. To search for signs of aging in hydra, we studied sexually differentiated Hydra oligactis at the individual and cellular levels. As a result, we found a significant decline in the capacities for food capture, contractile movements, and reproduction. More importantly, we discovered an exponential increase in the mortality rate of the population. These observations suggest that the degenerative process in H. oligactis represents the aging process. Furthermore, we found that the number of germ cells increased, whereas the number of somatic cells concomitantly decreased. The observed change of the cell composition is thus consistent with the "pleiotropy" theory of aging.}, } @article {pmid16987952, year = {2006}, author = {Lee, HR and Neumann, P and Macas, J and Jiang, J}, title = {Transcription and evolutionary dynamics of the centromeric satellite repeat CentO in rice.}, journal = {Molecular biology and evolution}, volume = {23}, number = {12}, pages = {2505-2520}, doi = {10.1093/molbev/msl127}, pmid = {16987952}, issn = {0737-4038}, mesh = {Base Sequence ; Binding Sites ; Centromere/chemistry ; Chromosomes, Plant ; Cloning, Molecular ; DNA, Plant/analysis ; DNA, Satellite/*analysis ; DNA-Binding Proteins/metabolism ; *Evolution, Molecular ; Genetic Variation ; Molecular Sequence Data ; Oryza/*genetics/*metabolism ; Phylogeny ; Plant Proteins/genetics/isolation & purification ; RNA, Small Interfering/biosynthesis ; Sequence Analysis, DNA ; Transcription, Genetic/*physiology ; }, abstract = {Satellite DNA is a major component of centromeric heterochromatin in most multicellular eukaryotes, where it is typically organized into megabase-sized tandem arrays. It has recently been demonstrated that small interfering RNAs (siRNAs) processed from centromeric satellite repeats can be involved in epigenetic chromatin modifications which appear to underpin centromere function. However, the structural organization and evolution of the centromeric satellite DNA is still poorly understood. We analyzed the centromeric satellite repeat arrays from rice chromosomes 1 and 8 and identified higher order structures and local homogenization of the CentO repeats in these 2 centromeres. We also cloned the CentO repeats from the CENH3-associated nucleosomes by a chromatin immunoprecipitation (ChIP)-based method. Sequence variability analysis of the ChIPed CentO repeats revealed a single variable domain within the repeat. We detected transcripts derived from both strands of the CentO repeats. The CentO transcripts are processed into siRNA, suggesting a potential role of this satellite repeat family in epigenetic chromatin modification.}, } @article {pmid16987840, year = {2006}, author = {Vineis, P and Berwick, M}, title = {The population dynamics of cancer: a Darwinian perspective.}, journal = {International journal of epidemiology}, volume = {35}, number = {5}, pages = {1151-1159}, doi = {10.1093/ije/dyl185}, pmid = {16987840}, issn = {0300-5771}, mesh = {Cell Transformation, Neoplastic/chemically induced/*genetics ; Cocarcinogenesis ; Environmental Exposure/adverse effects ; Evolution, Molecular ; Humans ; Male ; *Models, Biological ; Mutagens/toxicity ; Mutation ; Neoplasms/epidemiology/*etiology/genetics ; *Selection, Genetic ; }, abstract = {Carcinogenesis, at least for some types of cancer, can be interpreted as the consequence of selection of mutated cells similar to what, in the theory of evolution, occurs at the population level. Instead of considering a population of organisms, we can refer to a population of cells belonging to multicellular organisms. Many carcinogens are mutagens, and the observed geographic distribution of cancer is, at least in part, attributable to environmental mutagens. However, the rapid change in risk for some cancers after migration suggests that carcinogenesis involves--in addition to mutations--some late event that most probably consists of the selection of cells already carrying mutations. We review a few examples of such selective pressures: finasteride in prostate cancer, vitamin supplementation in smokers, acquired resistance to chemotherapy, peripheral resistance to insulin, and sunlight and mutations in melanoma. A disease model for such a hypothesis is represented by Paroxysmal Nocturnal Hemoglobinuria (PNH). Mutations can be present at birth, as in the case of PNH, and can have a frequency much higher than the occurrence of the corresponding disease (PNH or lymphocytic leukaemia in children). However, PNH does not require a mutator phenotype, only a mutant phenotype followed by selection. A characteristic feature of cancer, instead, is likely to be the development of the mutator phenotype. We propose a 'Darwinian' model of carcinogenesis. If the model is correct, it suggests that prevention is more complex than avoiding exposure to mutagens. Mutations and genetic instability can be already present at birth. Mutations can be selected in the course of life if they increase survival advantage of the cell under certain environmental circumstances. In addition, gene-environment interactions cannot be interpreted according to a simplified linear model (based on the 'analysis of variance' concept); experimental work suggests that a more comprehensive non-linear interpretation based on the idea of 'norm of reaction' is needed.}, } @article {pmid16983540, year = {2006}, author = {Dunn, CW and Wagner, GP}, title = {The evolution of colony-level development in the Siphonophora (Cnidaria:Hydrozoa).}, journal = {Development genes and evolution}, volume = {216}, number = {12}, pages = {743-754}, pmid = {16983540}, issn = {0949-944X}, mesh = {Animals ; *Biological Evolution ; Body Patterning/*physiology ; Hydrozoa/*classification/genetics ; Models, Biological ; Oceans and Seas ; Phylogeny ; Reproduction, Asexual ; Species Specificity ; }, abstract = {Evolutionary developmental biology has focused almost exclusively on multicellular organisms, but there are other relevant levels of biological organization that have remained largely neglected. Animal colonies are made up of multiple physiologically integrated and genetically identical units called zooids that are each homologous to solitary, free-living animals. Siphonophores, a group of pelagic hydrozoans (Cnidaria), have the most complex colony-level organization of all animals. Here the colony-level development of five siphonophore species, strategically sampled across the siphonophore phylogeny, is described from specimens collected using deep-sea submersibles and by self-contained underwater breathing apparatus diving. These species include three cystonects, Bathyphysa sibogae, Rhizophysa filiformis, and Rhizophysa eysenhardti, and two "physonects", Agalma elegans and Nanomia bijuga. These data, together with previous findings, are analyzed in a phylogenetic framework to reconstruct key features of the history of colony-level organization and development in the Siphonophora. It is shown that gonodendra and gastrozooids of the examined cystonects arise as independent buds directly on the stem, whereas probud subdivision (the origin of feeding, reproductive, and other zooids from a single bud) is a synapomorphy of the Codonophora. The origin of probud subdivision is associated with the origin of cormidia as integrated units of colony organization, and may have allowed for greater morphological and ecological diversification in the Codonophora relative to the Cystonectae. It is also found that symmetry is labile in siphonophores, with multiple gains and/or losses of directional asymmetry in the group. This descriptive work will enable future mechanistic and molecular studies of colony-level development in the siphonophores.}, } @article {pmid16983079, year = {2006}, author = {Sanjuán, R and Elena, SF}, title = {Epistasis correlates to genomic complexity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, number = {39}, pages = {14402-14405}, pmid = {16983079}, issn = {0027-8424}, mesh = {Animals ; Aspergillus/genetics ; Drosophila melanogaster/genetics ; *Epistasis, Genetic ; Escherichia coli/genetics ; Genome/*genetics ; Genome, Bacterial/genetics ; Genome, Fungal/genetics ; Genome, Insect/genetics ; Genome, Viral/genetics ; Meta-Analysis as Topic ; Saccharomyces cerevisiae/genetics ; Vesicular stomatitis Indiana virus/genetics ; }, abstract = {Whether systematic genetic interactions (epistasis) occur at the genomic scale remains a challenging topic in evolutionary biology. Epistasis should make a significant contribution to variation in complex traits and influence the evolution of genetic systems as sex, diploidy, dominance, or the contamination of genomes with deleterious mutations. We have collected data from widely different organisms and quantified epistasis in a common, per-generation scale. Simpler genomes, such as those of RNA viruses, display antagonistic epistasis (mutations have smaller effects together than expected); bacterial microorganisms do not apparently deviate from independent effects, whereas in multicellular eukaryotes, a transition toward synergistic epistasis occurs (mutations have larger effects together than expected). We propose that antagonistic epistasis might be a property of compact genomes with few nonpleiotropic biological functions, whereas in complex genomes, synergism might emerge from mutational robustness.}, } @article {pmid16967258, year = {2006}, author = {Chignola, R and Pra, PD and Morato, LM and Siri, P}, title = {Proliferation and death in a binary environment: a stochastic model of cellular ecosystems.}, journal = {Bulletin of mathematical biology}, volume = {68}, number = {7}, pages = {1661-1680}, doi = {10.1007/s11538-006-9078-8}, pmid = {16967258}, issn = {0092-8240}, mesh = {Algorithms ; Animals ; Cell Count ; Cell Death ; *Cell Physiological Phenomena ; *Cell Proliferation ; Extracellular Space/physiology ; Humans ; *Models, Biological ; Spheroids, Cellular/cytology/physiology ; *Stochastic Processes ; Tumor Cells, Cultured ; }, abstract = {The activation, growth and death of animal cells are accompanied by changes in the chemical composition of the surrounding environment. Cells and their microscopic environment constitute therefore a cellular ecosystem whose time-evolution determines processes of interest for either biology (e.g. animal development) and medicine (e.g. tumor spreading, immune response). In this paper, we consider a general stochastic model of the interplay between cells and environmental cellular niches. Niches may be either favourable or unfavourable in sustaining cell activation, growth and death, the state of the niches depending on the state of the cells. Under the hypothesis of random coupling between the state of the environmental niche and the state of the cell, the rescaled model reduces to a set of four non-linear differential equations. The biological meaning of the model is studied and illustrated by fitting experimental data on the growth of multicellular tumor spheroids. A detailed analysis of the stochastic model, of its deterministic limit, and of normal fluctuations is provided.}, } @article {pmid16960124, year = {2007}, author = {Perez-Vilar, J}, title = {Mucin granule intraluminal organization.}, journal = {American journal of respiratory cell and molecular biology}, volume = {36}, number = {2}, pages = {183-190}, pmid = {16960124}, issn = {1044-1549}, support = {DK67404/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Extracellular Matrix/metabolism ; Goblet Cells/cytology ; Humans ; Mucins/biosynthesis/chemistry/*metabolism ; Protein Transport ; Secretory Vesicles/*metabolism ; }, abstract = {Mucus secretions have played a central role in the evolution of multicellular organisms, enabling adaptation to widely differing environments. In vertebrates, mucus covers and protects the epithelial cells in the respiratory, gastrointestinal, urogenital, visual, and auditory systems, amphibian's epidermis, and the gills in fishes. Deregulation of mucus production and/or composition has important consequences for human health. For example, mucus obstruction of small airways is observed in chronic airway diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis. The major protein component in the mucus is a family of large, disulfide-bonded glycoproteins known as gel-forming mucins. These proteins are accumulated in large, regulated secretory granules (the mucin granules) that occupy most of the apical cytoplasm of specialized cells known as mucous/goblet cells. Since mucin oligomers have contour dimensions larger than the mucin granule average diameter, the question arises how these highly hydrophilic macromolecules are organized within these organelles. I review here the intraluminal organization of the mucin granule in view of our knowledge on the structure, biosynthesis, and biophysical properties of gel-forming mucins, and novel imaging studies in living mucous/goblet cells. The emerging concept is that the mucin granule lumen comprises a partially condensed matrix meshwork embedded in a fluid phase where proteins slowly diffuse.}, } @article {pmid16941207, year = {2006}, author = {Cong, B and Tanksley, SD}, title = {FW2.2 and cell cycle control in developing tomato fruit: a possible example of gene co-option in the evolution of a novel organ.}, journal = {Plant molecular biology}, volume = {62}, number = {6}, pages = {867-880}, pmid = {16941207}, issn = {0167-4412}, mesh = {Amino Acid Sequence ; Arabidopsis/genetics/growth & development/metabolism ; Biolistics/methods ; Casein Kinase II/genetics/metabolism ; Cell Cycle/*genetics ; Cell Membrane/metabolism ; Chromosome Mapping ; DNA, Complementary/genetics/metabolism ; Evolution, Molecular ; Fruit/*genetics/growth & development ; Gene Dosage ; Gene Expression Regulation, Plant ; Luminescent Proteins/genetics/metabolism ; Solanum lycopersicum/*genetics/growth & development ; Microscopy, Confocal ; Molecular Sequence Data ; Mutation/genetics ; Onions/cytology/metabolism ; Phylogeny ; Protein Binding ; Quantitative Trait Loci/*genetics ; Recombinant Fusion Proteins/genetics/metabolism ; Saccharomyces cerevisiae/genetics ; Sequence Homology, Amino Acid ; Two-Hybrid System Techniques ; }, abstract = {fw2.2 is one of the few QTLs thus far isolated from plants and the first one known to control fruit size. While it has been established that FW2.2 is a regulator (either directly or indirectly) of cell division, FW2.2 does not share sequence homology to any protein of known function (Frary et al. Science 289:85-88, 2000; Cong et al. Proc Natl Acad Sci USA 99:13606-13611, 2002; Liu et al. Plant Physiol 132:292-299, 2003). Thus, the mechanism by which FW2.2 mediates cell division in developing fruit is currently unknown. In an effort to remedy this situation, a combination of yeast two-hybrid screens, in vitro binding assays and cell bombardment studies were performed. The results provide strong evidence that FW2.2 physically interacts at or near the plasma membrane with the regulatory (beta) subunit of a CKII kinase. CKII kinases are well-studied in both yeast and animals where they form part of cell cycle related signaling pathway. Thus while FW2.2 is a plant-specific protein and regulates cell division in a specialized plant organ (fruit), it appears to participate in a cell-cycle control signal transduction pathway that predates the divergence of single- and multi-cellular organisms. These results thus provide a glimpse into how ancient and conserved regulatory processes can be co-opted in the evolution of novel organs such as fruit.}, } @article {pmid16937061, year = {2006}, author = {Pulido, A and Bakos, F and Castillo, A and Vallés, MP and Barnabás, B and Olmedilla, A}, title = {Influence of Fe concentration in the medium on multicellular pollen grains and haploid plants induced by mannitol pretreatment in barley (Hordeum vulgare L.).}, journal = {Protoplasma}, volume = {228}, number = {1-3}, pages = {101-106}, pmid = {16937061}, issn = {0033-183X}, mesh = {Biological Evolution ; *Haploidy ; Hordeum/cytology/*drug effects/ultrastructure ; Iron/*pharmacology ; Mannitol/*pharmacology ; Pectins/ultrastructure ; Pollen/cytology/*drug effects/ultrastructure ; Seeds/cytology/drug effects/ultrastructure ; }, abstract = {This study aims to clarify the short- and long-term effects of the iron concentration in the medium on androgenesis induced in barley by isolated microspore culture. The ultrastructural features and pectin composition of the intine wall were studied in the initial stages of androgenesis. The evolution of electron-dense iron deposits on the intine was analysed in multicellular pollen grains obtained by isolated microspore culture performed for 3, 6, and 9 days using various concentrations of FeNa(2) EDTA. Finally, the number of embryo-like structures and green plants obtained by microspore culture using different Fe concentrations was evaluated in order to estimate the optimum concentration for isolated microspore culture.}, } @article {pmid16923397, year = {2006}, author = {Bookout, AL and Jeong, Y and Downes, M and Yu, RT and Evans, RM and Mangelsdorf, DJ}, title = {Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network.}, journal = {Cell}, volume = {126}, number = {4}, pages = {789-799}, pmid = {16923397}, issn = {0092-8674}, support = {/HHMI/Howard Hughes Medical Institute/United States ; U19 DK062434/DK/NIDDK NIH HHS/United States ; U19DK62434/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cluster Analysis ; Databases, Factual ; Female ; Gene Expression Profiling ; Male ; Mice ; Mice, Inbred C57BL ; Multigene Family ; Phylogeny ; Receptors, Cytoplasmic and Nuclear/classification/genetics/*metabolism ; Tissue Distribution ; *Transcription, Genetic ; }, abstract = {In multicellular organisms, the ability to regulate reproduction, development, and nutrient utilization coincided with the evolution of nuclear receptors (NRs), transcription factors that utilize lipophilic ligands to mediate their function. Studying the expression profile of NRs offers a simple, powerful way to obtain highly relational information about their physiologic functions as individual proteins and as a superfamily. We surveyed the expression of all 49 mouse NR mRNAs in 39 tissues, representing diverse anatomical systems. The resulting data set uncovers several NR clades whose patterns of expression indicate their ability to coordinate the transcriptional programs necessary to affect distinct physiologic pathways. Remarkably, this regulatory network divides along the following two physiologic paradigms: (1) reproduction, development, and growth and (2) nutrient uptake, metabolism, and excretion. These data reveal a hierarchical transcriptional circuitry that extends beyond individual tissues to form a meganetwork governing physiology on an organismal scale.}, } @article {pmid16903215, year = {2006}, author = {Aleem, E and Kaldis, P}, title = {Mouse models of cell cycle regulators: new paradigms.}, journal = {Results and problems in cell differentiation}, volume = {42}, number = {}, pages = {271-328}, doi = {10.1007/400_023}, pmid = {16903215}, issn = {0080-1844}, support = {//Intramural NIH HHS/United States ; }, mesh = {Animals ; *Cell Cycle ; Cell Cycle Proteins/genetics/*physiology ; Gene Expression Regulation ; Humans ; Mice ; Mice, Transgenic ; Models, Genetic ; }, abstract = {In yeast, a single cyclin-dependent kinase (Cdk) is able to regulate diverse cell cycle transitions (S and M phases) by associating with multiple stage-specific cyclins. The evolution of multicellular organisms brought additional layers of cell cycle regulation in the form of numerous Cdks, cyclins and Cdk inhibitors to reflect the higher levels of organismal complexity. Our current knowledge about the mammalian cell cycle emerged from early experiments using human and rodent cell lines, from which we built the current textbook model of cell cycle regulation. In this model, the functions of different cyclin/Cdk complexes were thought to be specific for each cell cycle phase. In the last decade, studies using genetically engineered mice in which cell cycle regulators were targeted revealed many surprises. We discovered the in vivo functions of cell cycle proteins within the context of a living animal and whether they are essential for animal development. In this review, we discuss first the textbook model of cell cycle regulation, followed by a global overview of data obtained from different mouse models. We describe the similarities and differences between the phenotypes of different mouse models including embryonic lethality, sterility, hematopoietic, pancreatic, and placental defects. We also describe the role of key cell cycle regulators in the development of tumors in mice, and the implications of these data for human cancer. Furthermore, animal models in which two or more genes are ablated revealed which cell cycle regulators interact genetically and functionally complement each other. We discuss for example the interaction of cyclin D1 and p27 and the compensation of Cdk2 by Cdc2. We also focus on new functions discovered for certain cell cycle regulators such as the regulation of S phase by Cdc2 and the role of p27 in regulating cell migration. Finally, we conclude the chapter by discussing the limitations of animal models and to what extent can the recent findings be reconciled with the past work to come up with a new model for cell cycle regulation with high levels of redundancy among the molecular players.}, } @article {pmid16899276, year = {2006}, author = {Johnson, LR and Mangel, M}, title = {Life histories and the evolution of aging in bacteria and other single-celled organisms.}, journal = {Mechanisms of ageing and development}, volume = {127}, number = {10}, pages = {786-793}, doi = {10.1016/j.mad.2006.07.004}, pmid = {16899276}, issn = {0047-6374}, mesh = {Adaptation, Biological ; *Aging ; Bacteria/*metabolism ; *Bacterial Physiological Phenomena ; Escherichia coli/metabolism ; Models, Genetic ; Models, Statistical ; Models, Theoretical ; Time Factors ; }, abstract = {The disposable soma theory of aging was developed to explore how differences in lifespans and aging rates could be linked to life history trade-offs. Although generally applied for multicellular organisms, it is also useful for exploring life history strategies of single-celled organisms such as bacteria. Motivated by recent research of aging in E. coli, we explore the effects of aging on the fitness of simple single-celled organisms. Starting from the Euler-Lotka equation, we propose a mathematical model to explore how a finite reproductive lifespan affects fitness and resource allocation in simple organisms. This model provides quantitative predictions that have the potential for direct comparison with experiment, providing an opportunity to test the disposable soma theory more directly.}, } @article {pmid16897494, year = {2006}, author = {Xu, R and Zhao, H and Dinkins, RD and Cheng, X and Carberry, G and Li, QQ}, title = {The 73 kD subunit of the cleavage and polyadenylation specificity factor (CPSF) complex affects reproductive development in Arabidopsis.}, journal = {Plant molecular biology}, volume = {61}, number = {4-5}, pages = {799-815}, pmid = {16897494}, issn = {0167-4412}, mesh = {Arabidopsis/cytology/*metabolism ; Arabidopsis Proteins/*chemistry/*metabolism ; Cleavage And Polyadenylation Specificity Factor/*chemistry/*metabolism ; Flowers/anatomy & histology/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Molecular Sequence Data ; Molecular Weight ; Phylogeny ; Pollen/metabolism ; Protein Subunits/chemistry/metabolism ; Reproduction/physiology ; }, abstract = {The cleavage and polyadenylation specificity factor (CPSF) is an important multi-subunit component of the mRNA 3'-end processing apparatus in eukaryotes. The Arabidopsis genome contains five genes encoding CPSF homologues (AtCPSF160, AtCPSF100, AtCPSF73-I, AtCPSF73-II and AtCPSF30). These CPSF homologues interact with each other in a way that is analogous to the mammalian CPSF complex or their yeast counterparts, and also interact with the Arabidopsis poly(A) polymerase (PAP). There are two CPSF73 like proteins (AtCPSF73-I and AtCPSF73-II) that share homology with the 73 kD subunit of the mammalian CPSF complex. AtCPSF73-I appears to correspond to the functionally characterized mammalian CPSF73 and its yeast counterpart. AtCPSF73-II was identified as a novel protein with uncharacterized protein homologues in other multicellular organisms, but not in yeast. Both of the AtCPSF73 proteins are targeted in the nucleus and were found to interact with AtCPSF100. They are also essential since knockout or knockdown mutants are lethal. In addition, the expression level of AtCPSF73-I is critical for Arabidopsis development because overexpression of AtCPSF73-I is lethal. Interestingly, transgenic plants carrying an additional copy of the AtCPSF73-I gene, that is, the full-length cDNA under the control of its native promoter, appeared normal but were male sterile due to delayed anther dehiscence. In contrast, we previously demonstrated that a mutation in the AtCPSF73-II gene was detrimental to the genetic transmission of female gametes. Thus, two 73 kD subunits of the AtCPSF complex appear to have special functions during flower development. The important roles of mRNA 3'-end processing machinery in modulating plant development are discussed.}, } @article {pmid16893475, year = {2006}, author = {Schmidt, AL and Anderson, LM}, title = {Repetitive DNA elements as mediators of genomic change in response to environmental cues.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {81}, number = {4}, pages = {531-543}, doi = {10.1017/S146479310600710X}, pmid = {16893475}, issn = {1464-7931}, support = {//Intramural NIH HHS/United States ; }, mesh = {Animals ; DNA/*analysis ; DNA Transposable Elements/physiology ; *Environment ; *Evolution, Molecular ; Humans ; Microsatellite Repeats/physiology ; *Mutation ; Repetitive Sequences, Nucleic Acid/*physiology ; }, abstract = {There is no logical or theoretical barrier to the proposition that organismal and cell signaling could transduce environmental signals into specific, beneficial changes in primary structure of noncoding DNA via repetitive element movement or mutation. Repetitive DNA elements, including transposons and microsatellites, are known to influence the structure and expression of protein-coding genes, and to be responsive to environmental signals in some cases. These effects may create fodder for adaptive evolution, at rates exceeding those observed for point mutations. In many cases, the changes are no doubt random, and fitness is increased through simple natural selection. However, some transposons insert at specific sites, and certain regions of the genome exhibit selectively and beneficially high mutation rates in a range of organisms. In multicellular organisms, this could benefit individuals in situations with significant potential for clonal expansion: early life stages or regenerative tissues in animals, and most plant tissues. Transmission of the change to the next generation could occur in plants and, under some circumstances, in animals.}, } @article {pmid16887903, year = {2006}, author = {Liao, BY and Scott, NM and Zhang, J}, title = {Impacts of gene essentiality, expression pattern, and gene compactness on the evolutionary rate of mammalian proteins.}, journal = {Molecular biology and evolution}, volume = {23}, number = {11}, pages = {2072-2080}, doi = {10.1093/molbev/msl076}, pmid = {16887903}, issn = {0737-4038}, mesh = {Animals ; *Evolution, Molecular ; *Gene Expression ; *Genetic Variation ; Introns ; Mice ; Models, Genetic ; Proteins/*genetics ; Tissue Distribution/*genetics ; }, abstract = {Understanding the determinants of the rate of protein sequence evolution is of fundamental importance in evolutionary biology. Many recent studies have focused on the yeast because of the availability of many genome-wide expressional and functional data. Yeast studies revealed a predominant role of gene expression level and a minor role of gene essentiality in determining the rate of protein sequence evolution. Whether these rules apply to complex organisms such as mammals is unclear. Here we assemble a list of 1,138 essential and 2,341 nonessential mouse genes based on targeted gene deletion experiments and report a significant impact of gene essentiality on the rate of mammalian protein evolution. Gene expression level has virtually no effect, although tissue specificity in expression pattern has a strong influence. Unexpectedly, gene compactness, measured by average intron size and untranslated region length, has the greatest influence. Hence, the relative importance of the various factors in determining the rate of mammalian protein evolution is gene compactness > gene essentiality approximately tissue specificity > expression level. Our results suggest a considerable variation in rate determinants between unicellular organisms such as the yeast and multicellular organisms such as mammals.}, } @article {pmid16882515, year = {2006}, author = {Herkovits, J}, title = {Evoecotoxicology: environmental changes and life features development during the evolutionary process-the record of the past at developmental stages of living organisms.}, journal = {Environmental health perspectives}, volume = {114}, number = {8}, pages = {1139-1142}, pmid = {16882515}, issn = {0091-6765}, mesh = {Animals ; *Biological Evolution ; Biomarkers ; Chemical Phenomena ; Chemistry, Physical ; Embryonic Development/physiology ; *Environment ; Environmental Pollution ; Fossils ; Oxygen/physiology ; }, abstract = {For most of evolutionary history, scientific understanding of the environment and life forms is extremely limited. In this commentary I discuss the hypothesis that ontogenetic features of living organisms can be considered biomarkers of coevolution between organisms and physicochemical agents during Earth's history. I provide a new vision of evolution based on correlations between metabolic features and stage-dependent susceptibility of organisms to physicochemical agents with well-known environmental signatures. Thus, developmental features potentially reflect environmental changes during evolution. From this perspective, early multicellular life forms would have flourished in the anoxic Earth more than 2 billion years ago, which is at least 1.2 billion years in advance of available fossil evidence. The remarkable transition to aerobic metabolism in gastrula-stage embryos potentially reflects evolution toward tridermic organisms by 2 billion years ago. Noteworthy changes in embryonic resistance to physicochemical agents at different developmental stages that can be observed in living organisms potentially reflect the influence of environmental stress conditions during different periods of evolutionary history. Evoecotoxicology, as a multidisciplinary and transdisciplinary approach, can enhance our understanding of evolution, including the phylogenetic significance of differences in susceptibility/resistance to physicochemical agents in different organisms.}, } @article {pmid16877494, year = {2006}, author = {Yan, H and Ito, H and Nobuta, K and Ouyang, S and Jin, W and Tian, S and Lu, C and Venu, RC and Wang, GL and Green, PJ and Wing, RA and Buell, CR and Meyers, BC and Jiang, J}, title = {Genomic and genetic characterization of rice Cen3 reveals extensive transcription and evolutionary implications of a complex centromere.}, journal = {The Plant cell}, volume = {18}, number = {9}, pages = {2123-2133}, pmid = {16877494}, issn = {1040-4651}, mesh = {*Centromere ; Chromatin Immunoprecipitation ; Chromosome Mapping ; *Chromosomes, Plant ; DNA, Satellite/chemistry ; *Evolution, Molecular ; Genetic Linkage ; Genomics ; Histones/chemistry/metabolism ; In Situ Hybridization, Fluorescence ; Oryza/*genetics/metabolism ; Plant Proteins/chemistry/genetics/metabolism ; Protein Structure, Tertiary ; RNA, Messenger/metabolism ; RNA, Small Interfering/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; *Transcription, Genetic ; }, abstract = {The centromere is the chromosomal site for assembly of the kinetochore where spindle fibers attach during cell division. In most multicellular eukaryotes, centromeres are composed of long tracts of satellite repeats that are recalcitrant to sequencing and fine-scale genetic mapping. Here, we report the genomic and genetic characterization of the complete centromere of rice (Oryza sativa) chromosome 3. Using a DNA fiber-fluorescence in situ hybridization approach, we demonstrated that the centromere of chromosome 3 (Cen3) contains approximately 441 kb of the centromeric satellite repeat CentO. Cen3 includes an approximately 1,881-kb domain associated with the centromeric histone CENH3. This CENH3-associated chromatin domain is embedded within a 3,113-kb region that lacks genetic recombination. Extensive transcription was detected within the CENH3 binding domain based on comprehensive annotation of protein-coding genes coupled with empirical measurements of mRNA levels using RT-PCR and massively parallel signature sequencing. Genes <10 kb from the CentO satellite array were expressed in several rice tissues and displayed histone modification patterns consistent with euchromatin, suggesting that rice centromeric chromatin accommodates normal gene expression. These results support the hypothesis that centromeres can evolve from gene-containing genomic regions.}, } @article {pmid16873552, year = {2006}, author = {Segawa, Y and Suga, H and Iwabe, N and Oneyama, C and Akagi, T and Miyata, T and Okada, M}, title = {Functional development of Src tyrosine kinases during evolution from a unicellular ancestor to multicellular animals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, number = {32}, pages = {12021-12026}, pmid = {16873552}, issn = {0027-8424}, mesh = {Amino Acid Sequence ; Animals ; Cell Adhesion ; Cloning, Molecular ; *Evolution, Molecular ; Gene Expression Regulation ; Humans ; Molecular Sequence Data ; Phosphorylation ; Porifera ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry ; Saccharomyces cerevisiae ; src-Family Kinases/genetics/*physiology ; }, abstract = {The Src family of tyrosine kinases play pivotal roles in regulating cellular functions characteristic of multicellular animals, including cell-cell interactions, cell-substrate adhesion, and cell migration. To investigate the functional alteration of Src kinases during evolution from a unicellular ancestor to multicellular animals, we characterized Src orthologs from the unicellular choanoflagellate Monosiga ovata and the primitive multicellular sponge Ephydatia fluviatilis. Here, we show that the src gene family and its C-terminal Src kinase (Csk)-mediated regulatory system already were established in the unicellular M. ovata and that unicellular Src has unique features relative to multicellular Src: It can be phosphorylated by Csk at the negative regulatory site but still exhibits substantial activity even in the phosphorylated form. Analyses of chimera molecules between M. ovata and E. fluviatilis Src orthologs reveal that structural alterations in the kinase domain are responsible for the unstable negative regulation of M. ovata Src. When expressed in vertebrate fibroblasts, M. ovata Src can induce cell transformation irrespective of the presence of Csk. These findings suggest that a structure of Src required for the stable Csk-mediated negative regulation still is immature in the unicellular M. ovata and that the development of stable negative regulation of Src may correlate with the evolution of multicellularity in animals.}, } @article {pmid16859446, year = {2006}, author = {Federici, D and Downing, K}, title = {Evolution and development of a multicellular organism: scalability, resilience, and neutral complexification.}, journal = {Artificial life}, volume = {12}, number = {3}, pages = {381-409}, doi = {10.1162/artl.2006.12.3.381}, pmid = {16859446}, issn = {1064-5462}, mesh = {Algorithms ; *Biological Evolution ; Cell Proliferation ; Embryonic Development ; Gene Duplication ; *Models, Biological ; Models, Genetic ; Mutation ; Phenotype ; }, abstract = {To increase the evolvability of larger search spaces, several indirect encoding strategies have been proposed. Among these, multicellular developmental systems are believed to offer great potential for the evolution of general, scalable, and self-repairing organisms. We reinforce this view, presenting the results achieved by such a model and comparing it against direct encoding. Extra effort has been made to make this comparison both general and meaningful. Embryonal stages, a generic method showing increased evolvability and applicable to any developmental model, are introduced. Development with embryonal stages implements what we refer to as direct neutral complexification: direct genotype complexification by neutral duplication of expressed genes. The results show that, even for high-complexity evolutionary targets, the developmental model proves more scalable. The model also shows emergent self-repair, which is used to produce highly resilient organisms.}, } @article {pmid16854623, year = {2006}, author = {Hallmann, A}, title = {Morphogenesis in the family Volvocaceae: different tactics for turning an embryo right-side out.}, journal = {Protist}, volume = {157}, number = {4}, pages = {445-461}, doi = {10.1016/j.protis.2006.05.010}, pmid = {16854623}, issn = {1434-4610}, mesh = {Cell Division ; Chlorophyta/*growth & development ; Evolution, Molecular ; *Morphogenesis ; }, abstract = {Green algae of the family Volvocaceae provide an unrivalled opportunity to analyze an evolutionary pathway leading from unicellularity to multicellularity with division of labor. One key step required for achieving multicellularity in this group was the development of a process for turning an embryo inside out: a morphogenetic process that is now known as "inversion," and that is a diagnostic feature of the group. Inversion is essential because at the end of its embryonic cleavage divisions, each volvocacean embryo contains all of the cells that will be present in an adult, but the flagellar ends of all cells are pointed toward the interior, rather than toward the exterior where they will need to be to function in locomotion. Inversion has been studied in greatest detail in Volvox carteri, but although all other volvocacean species have to struggle with the same awkward situation of being wrong-side out at the end of cleavage, they do it in rather different ways. Here, the inversion processes of six different volvocacean species (Gonium pectorale, Pandorina morum, Eudorina unicocca, Volvox carteri, Volvox tertius, and Volvox globator) are compared, in order to illustrate the variation in inversion patterns that exists within this family. The simplest inversion process occurs in the plate-shaped alga Gonium pectorale and the most complicated in the spherical alga Volvox globator. Gonium pectorale goes only from a concave-bowl shape to a slightly convex plate. In Volvox globator, the posterior hemisphere inverts completely before the anterior pole opens and the anterior hemisphere slides over the already-inverted posterior hemisphere; during both halves of this inversion process, the regions of maximum cell-sheet curvature move progressively, as radially symmetrical waves, along the posterior-anterior axis.}, } @article {pmid16847462, year = {2006}, author = {Engelman, JA and Luo, J and Cantley, LC}, title = {The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism.}, journal = {Nature reviews. Genetics}, volume = {7}, number = {8}, pages = {606-619}, doi = {10.1038/nrg1879}, pmid = {16847462}, issn = {1471-0056}, support = {R01 GM041890/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Growth Processes/*physiology ; Cells/enzymology/*metabolism ; *Evolution, Molecular ; Humans ; Multigene Family ; Phosphatidylinositol 3-Kinases/*chemistry/classification/genetics/*physiology ; }, abstract = {Phosphatidylinositol 3-kinases (PI3Ks) evolved from a single enzyme that regulates vesicle trafficking in unicellular eukaryotes into a family of enzymes that regulate cellular metabolism and growth in multicellular organisms. In this review, we examine how the PI3K pathway has evolved to control these fundamental processes, and how this pathway is in turn regulated by intricate feedback and crosstalk mechanisms. In light of the recent advances in our understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, we discuss the exciting therapeutic opportunities for targeting this pathway to treat these diseases.}, } @article {pmid16845430, year = {2006}, author = {West, SA and Griffin, AS and Gardner, A and Diggle, SP}, title = {Social evolution theory for microorganisms.}, journal = {Nature reviews. Microbiology}, volume = {4}, number = {8}, pages = {597-607}, doi = {10.1038/nrmicro1461}, pmid = {16845430}, issn = {1740-1526}, mesh = {*Bacterial Physiological Phenomena ; Biofilms/growth & development ; *Biological Evolution ; Gene Expression Regulation, Bacterial ; }, abstract = {Microorganisms communicate and cooperate to perform a wide range of multicellular behaviours, such as dispersal, nutrient acquisition, biofilm formation and quorum sensing. Microbiologists are rapidly gaining a greater understanding of the molecular mechanisms involved in these behaviours, and the underlying genetic regulation. Such behaviours are also interesting from the perspective of social evolution - why do microorganisms engage in these behaviours given that cooperative individuals can be exploited by selfish cheaters, who gain the benefit of cooperation without paying their share of the cost? There is great potential for interdisciplinary research in this fledgling field of sociomicrobiology, but a limiting factor is the lack of effective communication of social evolution theory to microbiologists. Here, we provide a conceptual overview of the different mechanisms through which cooperative behaviours can be stabilized, emphasizing the aspects most relevant to microorganisms, the novel problems that microorganisms pose and the new insights that can be gained from applying evolutionary theory to microorganisms.}, } @article {pmid16845368, year = {2006}, author = {Grégoire, D and Brodolin, K and Méchali, M}, title = {HoxB domain induction silences DNA replication origins in the locus and specifies a single origin at its boundary.}, journal = {EMBO reports}, volume = {7}, number = {8}, pages = {812-816}, pmid = {16845368}, issn = {1469-221X}, mesh = {Acetylation ; Animals ; Cell Differentiation/drug effects/genetics/physiology ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; DNA Replication/*genetics ; Gene Expression Regulation/drug effects/*genetics ; Histones/genetics/metabolism ; Homeodomain Proteins/*genetics/metabolism ; Models, Genetic ; Origin Recognition Complex/genetics/metabolism ; Replication Origin/genetics ; Transcription, Genetic/drug effects/genetics ; Tretinoin/pharmacology ; }, abstract = {In multicellular organisms, changes in the DNA replication programme could act to integrate differentiation with cell division in various developmental and transcriptional contexts. Here, we have addressed the use of DNA replication origins during differentiation in the HoxB domain-a cluster of nine genes developmentally regulated in a collinear manner. In undifferentiated mouse P19 cells, we detected several DNA replication origins in the 100 kb HoxB locus, indicating a relaxed origin use when the locus is transcriptionally silent. By contrast, in retinoic-acid-induced differentiated cells, when HoxB transcription is activated, a general silencing of DNA replication origins occurs in the locus except one located downstream of Hoxb1, at the 3' boundary of the HoxB domain. Silencing of the replication origins is associated with histone hyperacetylation, whereas the active Hoxb1 origin persists as a hypoacetylated island. These findings provide direct evidence for the differentiated use of origins in HoxB genes, and we suggest that this regulation might contribute to the regulated expression of HoxB genes during development.}, } @article {pmid16830101, year = {2006}, author = {Vorobyov, E and Horst, J}, title = {Getting the proto-Pax by the tail.}, journal = {Journal of molecular evolution}, volume = {63}, number = {2}, pages = {153-164}, pmid = {16830101}, issn = {0022-2844}, mesh = {Amino Acid Sequence ; Animals ; Binding Sites/genetics ; Conserved Sequence/genetics ; Evolution, Molecular ; Humans ; Models, Genetic ; Molecular Sequence Data ; PAX2 Transcription Factor/genetics ; PAX7 Transcription Factor/genetics ; Paired Box Transcription Factors/*genetics ; *Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {Pax genes encode transcription factors governing the determination of different cell types and even organs in the development of multicellular animals. Pax proteins are characterized by the presence of three evolutionarily conserved elements: two DNA-binding domains, the paired domain (PD) and paired-type homeodomain (PtHD), and the short octopeptide sequence (OP) located between PD and PtHD. PD is the defining feature of this class of genes, while OP and/or PtHD may be divergent or absent in some members of the family. Phylogenetic analyses of the PD and PtHD sequences do not distinguish which particular type of the extant Pax genes more resembles the ancestral type. Here we present evidence for the existence of a fourth evolutionarily conserved domain in the Pax proteins, the paired-type homeodomain tail (PHT). Our data also imply that the hypothetical proto-Pax protein most probably exhibited a complex structure, PD-OP-PtHD-PHT, which has been retained in the extant proteins Pax3/7 of the ascidia and lancelet, and Pax7 of the vertebrates. Finally, based on structural considerations, a scenario for the evolutionary emergence of the proto-Pax gene is proposed.}, } @article {pmid16829700, year = {2006}, author = {Börner, U and Deutsch, A and Bär, M}, title = {A generalized discrete model linking rippling pattern formation and individual cell reversal statistics in colonies of myxobacteria.}, journal = {Physical biology}, volume = {3}, number = {2}, pages = {138-146}, doi = {10.1088/1478-3975/3/2/006}, pmid = {16829700}, issn = {1478-3975}, mesh = {Biological Evolution ; *Computer Simulation ; Linear Models ; *Models, Biological ; Myxococcales/*growth & development ; }, abstract = {Self-organization processes in multicellular aggregates of bacteria and amoebae offer fascinating insights into the evolution of cooperation and differentiation of cells. During myxobacterial development a variety of spatio-temporal patterns emerges such as counterpropagating waves of cell density that are known as rippling. Recently, several models have been introduced that qualitatively reproduce these patterns. All models include active motion and a collision-triggered reversal of individual bacteria. Here, we present a systematic study of a generalized discrete model that is based on similar assumptions as the continuous model by Igoshin et al (2001 Proc. Natl Acad. Sci. USA 98 14913). We find counterpropagating as well as unidirectional rippling waves in extended regions of the parameter space. If the interaction strength and the degree of cooperativity are large enough, rippling patterns appear even in the absence of a refractory period. We show for the first time that the experimentally observed double peak in the reversal statistics of bacteria in rippling colonies (Welch and Kaiser 2001 Proc. Natl Acad. Sci. USA 98 14907) can be reproduced in simulations of counterpropagating rippling waves which are dominant in experiments. In addition, the reversal statistics in the pre-rippling phase is correctly reproduced.}, } @article {pmid16824010, year = {2006}, author = {Lynch, M}, title = {Streamlining and simplification of microbial genome architecture.}, journal = {Annual review of microbiology}, volume = {60}, number = {}, pages = {327-349}, doi = {10.1146/annurev.micro.60.080805.142300}, pmid = {16824010}, issn = {0066-4227}, mesh = {Animals ; Arthropods/genetics ; Evolution, Molecular ; Genes, Mitochondrial ; Genetic Drift ; *Genetics, Microbial ; *Genome ; Genome, Bacterial ; Genome, Viral ; Mutation ; Operon ; Phenotype ; Symbiosis ; }, abstract = {The genomes of unicellular species, particularly prokaryotes, are greatly reduced in size and simplified in terms of gene structure relative to those of multicellular eukaryotes. Arguments proposed to explain this disparity include selection for metabolic efficiency and elevated rates of deletion in microbes, but the evidence in support of these hypotheses is at best equivocal. An alternative explanation based on fundamental population-genetic principles is proposed here. By increasing the mutational target sizes of associated genes, most forms of nonfunctional DNA are opposed by weak selection. Free-living microbial species have elevated effective population sizes, and the consequent reduction in the power of random genetic drift appears to be sufficient to enable natural selection to inhibit the accumulation of excess DNA. This hypothesis provides a potentially unifying explanation for the continuity in genomic scaling from prokaryotes to multicellular eukaryotes, the divergent patterns of mitochondrial evolution in animals and land plants, and various aspects of genomic modification in microbial endosymbionts.}, } @article {pmid16817991, year = {2006}, author = {Haag, KL and Gottstein, B and Müller, N and Schnorr, A and Ayala, FJ}, title = {Redundancy and recombination in the Echinococcus AgB multigene family: is there any similarity with protozoan contingency genes?.}, journal = {Parasitology}, volume = {133}, number = {Pt 4}, pages = {411-419}, doi = {10.1017/S0031182006000564}, pmid = {16817991}, issn = {0031-1820}, mesh = {Alleles ; Animals ; Antigens, Helminth/genetics ; Base Sequence ; DNA, Helminth ; Echinococcus/*genetics ; *Evolution, Molecular ; *Gene Conversion ; *Genes, Helminth ; *Genetic Variation ; Helminth Proteins/*genetics ; Lipoproteins/*genetics ; Molecular Sequence Data ; Multigene Family ; Polymerase Chain Reaction/methods ; Selection, Genetic ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Species Specificity ; }, abstract = {Numerous genetic variants of the Echinococcus antigen B (AgB) are encountered within a single metacestode. This could be a reflection of gene redundancy or the result of a somatic hypermutation process. We evaluate the complexity of the AgB multigene family by characterizing the upstream promoter regions of the 4 already known genes (EgAgB1-EgAgB4) and evaluating their redundancy in the genome of 3 Echinococcus species (E. granulosus, E. ortleppi and E. multilocularis) using PCR-based approaches. We have ascertained that the number of AgB gene copies is quite variable, both within and between species. The most repetitive gene seems to be AgB3, of which there are more than 110 copies in E. ortleppi. For E. granulosus, we have cloned and characterized 10 distinct upstream promoter regions of AgB3 from a single metacestode. Our sequences suggest that AgB1 and AgB3 are involved in gene conversion. These results are discussed in light of the role of gene redundancy and recombination in parasite evasion mechanisms of host immunity, which at present are known for protozoan organisms, but virtually unknown for multicellular parasites.}, } @article {pmid16817936, year = {2006}, author = {Lo, N and Beninati, T and Sassera, D and Bouman, EA and Santagati, S and Gern, L and Sambri, V and Masuzawa, T and Gray, JS and Jaenson, TG and Bouattour, A and Kenny, MJ and Guner, ES and Kharitonenkov, IG and Bitam, I and Bandi, C}, title = {Widespread distribution and high prevalence of an alpha-proteobacterial symbiont in the tick Ixodes ricinus.}, journal = {Environmental microbiology}, volume = {8}, number = {7}, pages = {1280-1287}, doi = {10.1111/j.1462-2920.2006.01024.x}, pmid = {16817936}, issn = {1462-2912}, mesh = {Alphaproteobacteria/*genetics/growth & development ; Animals ; Europe/epidemiology ; Female ; Infectious Disease Transmission, Vertical ; Ixodes/*microbiology ; Male ; Mitochondria/*microbiology ; Ovary/cytology/microbiology ; Phylogeny ; Prevalence ; RNA, Ribosomal, 16S/genetics ; *Symbiosis ; }, abstract = {The tick Ixodes ricinus is responsible for the transmission of a number of bacterial, protozoan and viral diseases to humans and animals in Europe and Northern Africa. Female I. ricinus from England, Switzerland and Italy have been found to harbour an intracellular alpha-proteobacterium, designated IricES1, within the cells of the ovary. IricES1 is the only prokaryote known to exist within the mitochondria of any animal or multicellular organism. To further examine the distribution, prevalence and mode of transmission of IricES1, we performed polymerase chain reaction screening of I. ricinus adults from 12 countries across its geographic distribution, including tick colonies that have been maintained in the laboratory for varying periods of time. IricES1 was detected in 100% of field-collected female ticks from all countries examined (n = 128), while 44% of males were found to be infected (n = 108). Those males that are infected appear to harbour fewer bacteria than females. Sequencing of fragments of the 16S rRNA and gyrB genes revealed very low nucleotide diversity among various populations of IricES1. Transmission of IricES1 from engorged adult females to eggs was found to be 100% (n = 31). In tick colonies that had been maintained in the laboratory for several years, a relatively low prevalence was found in females (32%; n = 25). To our knowledge, IricES1 is the most widespread and highly prevalent of any tick-associated symbiont.}, } @article {pmid16801682, year = {2006}, author = {Nicot, AS and Fares, H and Payrastre, B and Chisholm, AD and Labouesse, M and Laporte, J}, title = {The phosphoinositide kinase PIKfyve/Fab1p regulates terminal lysosome maturation in Caenorhabditis elegans.}, journal = {Molecular biology of the cell}, volume = {17}, number = {7}, pages = {3062-3074}, pmid = {16801682}, issn = {1059-1524}, support = {R01 GM054657/GM/NIGMS NIH HHS/United States ; R01 GM065235/GM/NIGMS NIH HHS/United States ; GM-54657/GM/NIGMS NIH HHS/United States ; GM-65235/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans/*enzymology/ultrastructure ; Caenorhabditis elegans Proteins/analysis/genetics/*physiology ; Intracellular Membranes/enzymology/*ultrastructure ; Lysosomes/enzymology/*ultrastructure ; Molecular Sequence Data ; Mutation ; Phosphatidylinositol Phosphates/analysis/metabolism ; Phosphotransferases (Alcohol Group Acceptor)/analysis/genetics/*physiology ; Vacuoles/enzymology/ultrastructure ; }, abstract = {Membrane dynamics is necessary for cell homeostasis and signal transduction and is in part regulated by phosphoinositides. Pikfyve/Fab1p is a phosphoinositide kinase that phosphorylates phosphatidylinositol 3-monophosphate into phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P2] and is implicated in membrane homeostasis in yeast and in mammalian cells. These two phosphoinositides are substrates of myotubularin phosphatases found mutated in neuromuscular diseases. We studied the roles of phosphatidylinositol phosphate kinase 3 (PPK-3), the orthologue of PIKfyve/Fab1p, in a multicellular organism, Caenorhabditis elegans. Complete loss of ppk-3 function induces developmental defects characterized by embryonic lethality, whereas partial loss of function leads to growth retardation. At the cellular level, ppk-3 mutants display a striking enlargement of vacuoles positive for lysosome-associated membrane protein 1 in different tissues. In the intestine, RAB-7-positive late endosomes are also enlarged. Membranes of the enlarged lysosomes originate at least in part from smaller lysosomes, and functional and genetic analyses show that the terminal maturation of lysosomes is defective. Protein degradation is not affected in the hypomorphic ppk-3 mutant and is thus uncoupled from membrane retrieval. We measured the level of PtdIns(3,5)P2 and showed that its production is impaired in this mutant. This work strongly suggests that the main function of PPK-3 is to mediate membrane retrieval from matured lysosomes through regulation of PtdIns(3,5)P2.}, } @article {pmid16796673, year = {2006}, author = {Kang, S and Barak, Y and Lamed, R and Bayer, EA and Morrison, M}, title = {The functional repertoire of prokaryote cellulosomes includes the serpin superfamily of serine proteinase inhibitors.}, journal = {Molecular microbiology}, volume = {60}, number = {6}, pages = {1344-1354}, doi = {10.1111/j.1365-2958.2006.05182.x}, pmid = {16796673}, issn = {0950-382X}, mesh = {Amino Acid Sequence ; Bacterial Proteins/genetics/*metabolism ; Cellulosomes/*metabolism ; Clostridium thermocellum/genetics/*metabolism ; *Genes, Bacterial ; Molecular Sequence Data ; Phylogeny ; Serine Proteinase Inhibitors/classification/genetics/*metabolism ; Serpins/classification/genetics/*metabolism ; }, abstract = {Many of the Firmicutes bacteria responsible for plant polysaccharide degradation in Nature produce a multiprotein complex called a cellulosome, which co-ordinates glycoside hydrolase assembly, bacterial adhesion to substrate and polysaccharide hydrolysis. Cellulosomal proteins possess a dockerin module, which mediates their attachment to the scaffoldin protein via its interaction with cohesin modules, and only glycoside hydrolases and other carbohydrate active enzymes were known to reside within the cellulosome. We show here with Clostridium thermocellum ATCC 27405 that members of the serpin superfamily of serine proteinase inhibitors, which are best recognized for their conformational flexibility and co-ordination of key regulatory functions in multicellular eukaryotes, also reside within the cellulosome. These studies are the first to expand the cellulosome paradigm of protein complex assembly beyond glycoside hydrolase and carbohydrate active enzymes, and to include a newly identified functionality in the Firmicutes.}, } @article {pmid16781008, year = {2006}, author = {Rosel, D and Kimmel, AR}, title = {The COP9 signalosome regulates cell proliferation of Dictyostelium discoideum.}, journal = {European journal of cell biology}, volume = {85}, number = {9-10}, pages = {1023-1034}, doi = {10.1016/j.ejcb.2006.04.006}, pmid = {16781008}, issn = {0171-9335}, support = {//Intramural NIH HHS/United States ; }, mesh = {Animals ; COP9 Signalosome Complex ; *Cell Proliferation ; Dictyostelium/cytology/*physiology ; Multiprotein Complexes/*metabolism ; Peptide Hydrolases/*metabolism ; Protozoan Proteins/metabolism ; }, abstract = {Regulated protein destruction involving SCF (Skp1/Cullin/F-box, E3 ubiquitin ligase) complexes is required for multicellular development of Dictyostelium discoideum. Dynamic modification of cullin by nedd8 is required for the proper action of SCF. The COP9 signalosome (CSN), first identified in a signaling pathway for light response in plants, functions as a large multi-protein complex that regulates cullin neddylation in eukaryotes. Still, there is extreme sequence divergence of CSN subunits of the yeasts in comparison to the multicellular plants and animals. Using the yeast two-hybrid system, we have identified the CSN5 subunit as a potential interacting partner of a cell surface receptor of Dictyostelium. We further identified and characterized all 8 CSN subunits in Dictyostelium discoideum. Remarkably, despite the ancient origin of Dictyostelium, its CSN proteins cluster very closely with their plant and animal counterparts. We additionally show that the Dictyostelium subunits, like those of other systems are capable of multi-protein interactions within the CSN complex. Our data also indicate that CSN5 (and CSN2) are essential for cell proliferation in Dictyostelium, a phenotype similar to that of multicellular organisms, but distinct from that of the yeasts. Finally, we speculate on a potential role of CSN in cullin function and regulated protein destruction during multicellular development of Dictyostelium.}, } @article {pmid16778307, year = {2006}, author = {Shaha, C}, title = {Apoptosis in Leishmania species & its relevance to disease pathogenesis.}, journal = {The Indian journal of medical research}, volume = {123}, number = {3}, pages = {233-244}, pmid = {16778307}, issn = {0971-5916}, mesh = {Animals ; Antiprotozoal Agents/pharmacology ; *Apoptosis ; Calcium/metabolism ; DNA Fragmentation ; Humans ; Hydrogen Peroxide/pharmacology ; Ions ; Leishmania/*metabolism ; Leishmaniasis/*enzymology/parasitology/physiopathology ; Mitochondria/*metabolism ; Trypanosoma ; }, abstract = {Apoptosis is a morphologically distinct form of cell death necessary for embryogenesis, tissue homeostasis and disease control in metazoans. Earlier, it was thought that apoptosis is the prerogative of multicellular organisms. However, it is now evident that unicellular organisms are also capable of undergoing apoptosis. In the context of Leishmania spp., a unicellular eukaryote responsible for causing leishmaniasis, the process of apoptosis is important for successful survival. The flagellated promastigote form of the parasite resides in the midgut of the insect vector, the female sandfly and at this niche; the cell fittest to survive to pass onto the pharynx of the fly is selected by eliminating unfit cells through apoptosis. Within the mammalian host, inside the macrophage, apoptosis is necessary to regulate cell numbers and to minimize immune reactions. With most apoptosis inducing stimuli, L. donovani shows typical features of apoptotic death like cell shrinkage, nuclear condensation and DNA fragmentation. Agents capable of precipitating apoptosis in this parasite include anti-leishmanial drugs like antimony, amphotericin B, pentamidine and miltefosine. Other agents like heat shock, treatment with staurosporine, knocking out centrin gene also precipitate apoptosis of the parasites. A pivotal role in cellular apoptosis is played by the single mitochondrion of Leishmania spp., where a fall or increase in mitochondrial potential leads to cell death by apoptosis. Ca2+ appears to be a vital ion involved in Leishmania apoptosis and partial inhibition of cytosolic Ca2+ increase achieved by chelating extracellular or intracellular Ca2+ during oxidative stress results in significant rescue of the fall of the mitochondrial membrane potential and consequently apoptosis. Elucidation of the molecular events linked to apoptotic death of Leishmania spp. might help define a more comprehensive view of the cell death machinery in terms of evolutionary origin and identify new target molecules for chemotherapeutic drug development and therapeutic intervention.}, } @article {pmid16762387, year = {2006}, author = {Costas, E and Lopez-Rodas, V}, title = {Copper sulphate and DCMU-herbicide treatments increase asymmetry between sister cells in the toxic cyanobacteria Microcystis aeruginosa: implications for detecting environmental stress.}, journal = {Water research}, volume = {40}, number = {12}, pages = {2447-2451}, doi = {10.1016/j.watres.2006.04.013}, pmid = {16762387}, issn = {0043-1354}, mesh = {Bacterial Toxins/*chemistry ; Copper Sulfate/chemistry/*pharmacology ; Diuron/chemistry/*pharmacology ; *Environmental Exposure ; Eukaryota/drug effects/growth & development ; Herbicides/chemistry/*pharmacology ; Microcystis/drug effects/*growth & development ; Oxidative Stress/*physiology ; }, abstract = {Works correlating fluctuating asymmetry with environmental stress or genetic damages have been largely reported in multicellular organisms but not in single-celled ones. We hypothesize that asymmetry analysis could also be applied to single-celled organisms, because the asymmetry between two sister cells originated from a cellular division event (same genotype in similar environment) must tend to zero in the absence of environmental or genetic perturbations. Laboratory experiments with copper sulphate and DCMU-herbicide treatments as well as experiments in a water reservoir after treatment with copper sulphate algaecide show that environmental stress increases asymmetry between sister cells of Microcystis aeruginosa (Cyanobacteria). Even low Cu(2+) or DCMU doses, which were unable to reduce growth rate, considerably enlarge asymmetry with respect to untreated controls. Asymmetry between sister cells of cyanobacteria seems to be a reliable indicator of environmental perturbation. Analysis of asymmetry in single-celled organisms could become as important as fluctuating asymmetry of multicellular organisms is today.}, } @article {pmid16751277, year = {2006}, author = {Michod, RE}, title = {The group covariance effect and fitness trade-offs during evolutionary transitions in individuality.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, number = {24}, pages = {9113-9117}, pmid = {16751277}, issn = {0027-8424}, mesh = {Animals ; *Biological Evolution ; *Genetic Variation ; Models, Genetic ; Reproduction/genetics ; Selection, Genetic ; }, abstract = {Transforming our understanding of life is the realization that evolution occurs not only among individuals within populations but also through the integration of groups of preexisting individuals into a new higher-level individual, that is, through evolutionary transitions in individuality. During evolutionary transitions (such as during the origin of gene networks, bacteria-like cells, eukaryotic cells, multicellular organisms, and societies), fitness must be reorganized; specifically, it must be transferred from the lower- to the higher-level units and partitioned among the lower-level units that specialize in the fitness components of the new higher-level individual. This paper studies the role of fitness trade-offs in fitness reorganization, the evolution of cooperation, and the conversion of a group into a new individual during the origin of multicellular life. Specifically, this study shows that the fitness of the group is augmented over the average fitness of its members according to a covariance effect. This covariance effect appears to be one of the first emergent properties of the group and a general aspect of groups with multiplicative properties that are themselves averages of properties of lower-level units. The covariance effect allows groups to break through the constraints that govern their members, and this effect likely applies to group dynamics in other fields.}, } @article {pmid16751096, year = {2006}, author = {Boehm, T}, title = {Quality control in self/nonself discrimination.}, journal = {Cell}, volume = {125}, number = {5}, pages = {845-858}, doi = {10.1016/j.cell.2006.05.017}, pmid = {16751096}, issn = {0092-8674}, mesh = {Animals ; Eukaryotic Cells/*immunology ; Evolution, Molecular ; Fungi/immunology ; Humans ; Immunity, Innate/*physiology ; Immunologic Surveillance/*immunology ; Killer Cells, Natural/immunology ; Peptides/immunology ; Plants/immunology ; Receptors, Antigen/*immunology ; Reproduction/physiology ; }, abstract = {Unicellular eukaryotes primarily employ self/nonself discrimination to avoid self-mating, whereas multicellular organisms also use self/nonself discrimination in immune defense. Recent advances in understanding self/nonself discrimination in eukaryotes shed new light on the emergence of the most sophisticated self/nonself discrimination system known, the antigen receptors employed in the adaptive immune system.}, } @article {pmid16738572, year = {2006}, author = {Andrianantoandro, E and Basu, S and Karig, DK and Weiss, R}, title = {Synthetic biology: new engineering rules for an emerging discipline.}, journal = {Molecular systems biology}, volume = {2}, number = {}, pages = {2006.0028}, pmid = {16738572}, issn = {1744-4292}, mesh = {Cells ; Engineering/*methods ; Genetic Engineering ; *Models, Biological ; Protein Engineering ; }, abstract = {Synthetic biologists engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications. We outline the basic features of synthetic biology as a new engineering discipline, covering examples from the latest literature and reflecting on the features that make it unique among all other existing engineering fields. We discuss methods for designing and constructing engineered cells with novel functions in a framework of an abstract hierarchy of biological devices, modules, cells, and multicellular systems. The classical engineering strategies of standardization, decoupling, and abstraction will have to be extended to take into account the inherent characteristics of biological devices and modules. To achieve predictability and reliability, strategies for engineering biology must include the notion of cellular context in the functional definition of devices and modules, use rational redesign and directed evolution for system optimization, and focus on accomplishing tasks using cell populations rather than individual cells. The discussion brings to light issues at the heart of designing complex living systems and provides a trajectory for future development.}, } @article {pmid16738111, year = {2006}, author = {Yamada, T and Sekiguchi, Y and Hanada, S and Imachi, H and Ohashi, A and Harada, H and Kamagata, Y}, title = {Anaerolinea thermolimosa sp. nov., Levilinea saccharolytica gen. nov., sp. nov. and Leptolinea tardivitalis gen. nov., sp. nov., novel filamentous anaerobes, and description of the new classes Anaerolineae classis nov. and Caldilineae classis nov. in the bacterial phylum Chloroflexi.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {56}, number = {Pt 6}, pages = {1331-1340}, doi = {10.1099/ijs.0.64169-0}, pmid = {16738111}, issn = {1466-5026}, mesh = {Chloroflexi/*classification/genetics/growth & development/isolation & purification ; Culture Media ; Microscopy, Phase-Contrast ; Molecular Sequence Data ; Phylogeny ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {One thermophilic (strain IMO-1(T)) and two mesophilic (strains KIBI-1(T) and YMTK-2(T)) non-spore-forming, non-motile, Gram-negative, multicellular filamentous micro-organisms, which were previously isolated as members of the tentatively named class 'Anaerolineae' of the phylum Chloroflexi, were characterized. All isolates were strictly anaerobic micro-organisms. The length of the three filamentous isolates was greater than 100 microm and the width was 0.3-0.4 microm for strain IMO-1(T), 0.4-0.5 microm for strain KIBI-1(T) and thinner than 0.2 microm for strain YMTK-2(T). Strain IMO-1(T) could grow at pH 6.0-7.5 (optimum growth at pH 7.0). The optimal temperature for growth of strain IMO-1(T) was around 50 degrees C (growth occurred between 42 and 55 degrees C). Growth of the mesophilic strains KIBI-1(T) and YMTK-2(T) occurred at pH 6.0-7.2 with optimal growth at pH 7.0. Both of the mesophilic strains were able to grow in a temperature range of 25-50 degrees C with optimal growth at around 37 degrees C. Yeast extract was required for growth of all three strains. All the strains could grow with a number of carbohydrates in the presence of yeast extract. The G + C contents of the DNA of strains IMO-1(T), KIBI-1(T) and YMTK-2(T) were respectively 53.3, 59.5 and 48.2 mol%. Major fatty acids for thermophilic strain IMO-1(T) were anteiso-C(17 : 0), iso-C(15 : 0), C(16 : 0) and anteiso-C(15 : 0), whereas those for mesophilic strains KIBI-1(T) and YMTK-2(T) were branched C(14 : 0), iso-C(15 : 0), C(16 : 0) and branched C(17 : 0), and branched C(17 : 0), C(16 : 0), C(14 : 0) and C(17 : 0), respectively. Detailed phylogenetic analyses based on their 16S rRNA gene sequences indicated that the isolates belong to the class-level taxon 'Anaerolineae' of the bacterial phylum Chloroflexi, which for a long time had been considered as a typical uncultured clone cluster. Their morphological, physiological, chemotaxonomic and genetic traits strongly support the conclusion that these strains should be described as three novel independent taxa in the phylum Chloroflexi. Here, Anaerolinea thermolimosa sp. nov. (type strain IMO-1(T) = CM 12577(T) = DSM 16554(T)), Levilinea saccharolytica gen. nov., sp. nov. (type strain KIBI-1(T) = JCM 12578(T) = DSM 16555(T)) and Leptolinea tardivitalis gen. nov., sp. nov. (type strain YMTK-2(T) = JCM 12579(T) = DSM 16556(T)) are proposed. In addition, we formally propose to subdivide the tentative class-level taxon 'Anaerolineae' into Anaerolineae classis nov. and Caldilineae classis nov. We also propose the subordinate taxa Anaerolineales ord. nov., Caldilineales ord. nov., Anaerolineaceae fam. nov. and Caldilineaceae fam. nov.}, } @article {pmid16737711, year = {2006}, author = {Berry, KL and Hobert, O}, title = {Mapping functional domains of chloride intracellular channel (CLIC) proteins in vivo.}, journal = {Journal of molecular biology}, volume = {359}, number = {5}, pages = {1316-1333}, doi = {10.1016/j.jmb.2006.04.046}, pmid = {16737711}, issn = {0022-2836}, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans/cytology ; Caenorhabditis elegans Proteins/chemistry/metabolism ; Cell Membrane/metabolism ; Chloride Channels/*chemistry/*metabolism ; Drosophila melanogaster ; Glutathione Transferase/chemistry/metabolism ; Humans ; Molecular Sequence Data ; Mutation/genetics ; Phenotype ; Phylogeny ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Transport ; Recombinant Fusion Proteins/metabolism ; Sequence Alignment ; Sequence Analysis, Protein ; }, abstract = {Chloride intracellular channel (CLIC) proteins are small proteins distantly related to the omega family of glutathione S-transferases (GSTs). CLIC proteins are expressed in a wide variety of tissues in multicellular organisms and are targeted to specific cellular membranes. Members of this family are capable in vitro of changing conformation from a globular, soluble state to a membrane-inserted state in which they provide chloride conductance. The structural basis for in vivo CLIC protein function, however, is not well understood. We have mapped the functional domains of CLIC family members using an in vivo assay for membrane localization and function of CLIC proteins in the nematode Caenorhabditis elegans. A<70 amino acid N-terminal domain is a key determinant of membrane localization and function of invertebrate CLIC proteins. This domain, which we term the ''PTM'' domain, named after an amphipathic putative transmembrane helix contained within it, directs distinct C. elegans CLIC homologs to distinct subcellular membranes. We find that within the PTM region, the cysteine residues required for GST-type activity are unnecessary for invertebrate CLIC function, but that specific residues within the proposed transmembrane helix are necessary for correct targeting and protein function. We find that among all tested invertebrate CLIC proteins, function appears to be completely conserved despite striking differences in the charged residues contained within the amphipathic helix. This indicates that these residues do not contribute to anion selectivity as previously suggested. We find that outside the PTM region, the remaining three-quarters of CLIC protein sequence is functionally equivalent not only among vertebrate and invertebrate CLIC proteins, but also among the more distantly related GST-omega and GST-sigma proteins. The PTM region thus provides both targeting information and CLIC functional specificity, possibly adapting GST-type proteins to function as ion channels.}, } @article {pmid16733546, year = {2006}, author = {Vogel, C and Chothia, C}, title = {Protein family expansions and biological complexity.}, journal = {PLoS computational biology}, volume = {2}, number = {5}, pages = {e48}, pmid = {16733546}, issn = {1553-7358}, support = {MC_U105184318/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Cluster Analysis ; Computational Biology/*methods ; Databases, Factual ; Evolution, Molecular ; Genes, Fungal ; Genes, Plant ; Humans ; Models, Biological ; Software ; }, abstract = {During the course of evolution, new proteins are produced very largely as the result of gene duplication, divergence and, in many cases, combination. This means that proteins or protein domains belong to families or, in cases where their relationships can only be recognised on the basis of structure, superfamilies whose members descended from a common ancestor. The size of superfamilies can vary greatly. Also, during the course of evolution organisms of increasing complexity have arisen. In this paper we determine the identity of those superfamilies whose relative sizes in different organisms are highly correlated to the complexity of the organisms. As a measure of the complexity of 38 uni- and multicellular eukaryotes we took the number of different cell types of which they are composed. Of 1,219 superfamilies, there are 194 whose sizes in the 38 organisms are strongly correlated with the number of cell types in the organisms. We give outline descriptions of these superfamilies. Half are involved in extracellular processes or regulation and smaller proportions in other types of activity. Half of all superfamilies have no significant correlation with complexity. We also determined whether the expansions of large superfamilies correlate with each other. We found three large clusters of correlated expansions: one involves expansions in both vertebrates and plants, one just in vertebrates, and one just in plants. Our work identifies important protein families and provides one explanation of the discrepancy between the total number of genes and the apparent physiological complexity of eukaryotic organisms.}, } @article {pmid16731622, year = {2006}, author = {Dellaporta, SL and Xu, A and Sagasser, S and Jakob, W and Moreno, MA and Buss, LW and Schierwater, B}, title = {Mitochondrial genome of Trichoplax adhaerens supports placozoa as the basal lower metazoan phylum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, number = {23}, pages = {8751-8756}, pmid = {16731622}, issn = {0027-8424}, mesh = {Animals ; DNA, Mitochondrial/*genetics ; Genome/*genetics ; Invertebrates/*classification/*genetics ; Molecular Sequence Data ; Phylogeny ; }, abstract = {Mitochondrial genomes of multicellular animals are typically 15- to 24-kb circular molecules that encode a nearly identical set of 12-14 proteins for oxidative phosphorylation and 24-25 structural RNAs (16S rRNA, 12S rRNA, and tRNAs). These genomes lack significant intragenic spacers and are generally without introns. Here, we report the complete mitochondrial genome sequence of the placozoan Trichoplax adhaerens, a metazoan with the simplest known body plan of any animal, possessing no organs, no basal membrane, and only four different somatic cell types. Our analysis shows that the Trichoplax mitochondrion contains the largest known metazoan mtDNA genome at 43,079 bp, more than twice the size of the typical metazoan mtDNA. The mitochondrion's size is due to numerous intragenic spacers, several introns and ORFs of unknown function, and protein-coding regions that are generally larger than those found in other animals. Not only does the Trichoplax mtDNA have characteristics of the mitochondrial genomes of known metazoan outgroups, such as chytrid fungi and choanoflagellates, but, more importantly, it shares derived features unique to the Metazoa. Phylogenetic analyses of mitochondrial proteins provide strong support for the placement of the phylum Placozoa at the root of the Metazoa.}, } @article {pmid16730849, year = {2006}, author = {Dujon, B}, title = {Yeasts illustrate the molecular mechanisms of eukaryotic genome evolution.}, journal = {Trends in genetics : TIG}, volume = {22}, number = {7}, pages = {375-387}, doi = {10.1016/j.tig.2006.05.007}, pmid = {16730849}, issn = {0168-9525}, mesh = {DNA Transposable Elements ; *Evolution, Molecular ; *Genome, Fungal ; Introns ; *Phylogeny ; Tandem Repeat Sequences ; Yeasts/*genetics ; }, abstract = {Hemiascomycetous yeasts have the greatest number of sequenced species for a single phylum, and are at the forefront of evolutionary genomics of eukaryotes. Yeast genomes show the dynamic interplay between the formation and loss of genes and help to characterize the mechanisms involved and their functional and evolutionary consequences. These mechanisms have equivalents in the genomes of multicellular organisms. Yeast genomes show extensive loss of introns and a reduced role of transposable elements, and so probably have a more limited potential to form novel genes and functions than multicellular organisms, possibly explaining their conserved biological and morphological properties despite their considerable evolutionary range.}, } @article {pmid16724262, year = {2006}, author = {Scofield, S and Murray, JA}, title = {KNOX gene function in plant stem cell niches.}, journal = {Plant molecular biology}, volume = {60}, number = {6}, pages = {929-946}, pmid = {16724262}, issn = {0167-4412}, mesh = {Arabidopsis/anatomy & histology/genetics/*metabolism ; Arabidopsis Proteins/chemistry/genetics/metabolism/*physiology ; Body Patterning ; Gene Expression Regulation, Plant ; Homeodomain Proteins/chemistry/genetics/*physiology ; Meristem/genetics/*metabolism ; Models, Biological ; Phylogeny ; Plant Growth Regulators/metabolism ; Protein Structure, Tertiary ; Reproduction ; Signal Transduction ; Stem Cells/*metabolism ; Transcription Factors/metabolism ; }, abstract = {Homeobox genes encode transcriptional regulators that control development in multicellular eukaryotes. In plants, post-embryonic shoot growth relies on the activity of indeterminate cell populations termed shoot meristems, within which members of the class-1 KNOX sub-family of homeobox genes are expressed. KNOX genes are differentially required for meristem development and function to inhibit cell expansion and differentiation associated with organogenesis. Mechanisms must therefore be employed to prevent KNOX gene expression in developing lateral organs such as leaves. This review focuses on the expression patterns, meristematic functions and regulation of KNOX genes, and how the activities of these genes are integrated within the framework of pathways that control plant development.}, } @article {pmid16720695, year = {2006}, author = {Nedelcu, AM and Michod, RE}, title = {The evolutionary origin of an altruistic gene.}, journal = {Molecular biology and evolution}, volume = {23}, number = {8}, pages = {1460-1464}, doi = {10.1093/molbev/msl016}, pmid = {16720695}, issn = {0737-4038}, mesh = {Algal Proteins/*genetics ; *Altruism ; Amino Acid Sequence ; Evolution, Molecular ; *Gene Expression Regulation, Plant ; Molecular Sequence Data ; Phylogeny ; Reproduction/genetics ; Sequence Homology, Amino Acid ; Transcription, Genetic ; Volvox/*genetics/physiology ; }, abstract = {Although the conditions favoring altruism are being increasingly understood, the evolutionary origins of the genetic basis for this behavior remain elusive. Here, we show that reproductive altruism (i.e., a sterile soma) in the multicellular green alga, Volvox carteri, evolved via the co-option of a life-history gene whose expression in the unicellular ancestor was conditioned on an environmental cue (as an adaptive strategy to enhance survival at an immediate cost to reproduction) through shifting its expression from a temporal (environmentally induced) into a spatial (developmental) context. The gene belongs to a diverged and structurally heterogeneous multigene family sharing a SAND-like domain (a DNA-binding module involved in gene transcription regulation). To our knowledge, this is the first example of a social gene specifically associated with reproductive altruism, whose origin can be traced back to a solitary ancestor. These findings complement recent proposals that the differentiation of sterile castes in social insects involved the co-option of regulatory networks that control sequential shifts between phases in the life cycle of solitary insects.}, } @article {pmid16717195, year = {2006}, author = {Romero, PR and Zaidi, S and Fang, YY and Uversky, VN and Radivojac, P and Oldfield, CJ and Cortese, MS and Sickmeier, M and LeGall, T and Obradovic, Z and Dunker, AK}, title = {Alternative splicing in concert with protein intrinsic disorder enables increased functional diversity in multicellular organisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, number = {22}, pages = {8390-8395}, pmid = {16717195}, issn = {0027-8424}, support = {R01 LM007688/LM/NLM NIH HHS/United States ; 5R01 LM 007688-02/LM/NLM NIH HHS/United States ; }, mesh = {*Alternative Splicing ; Animals ; Humans ; Models, Molecular ; Protein Conformation ; Protein Isoforms/genetics/metabolism ; Proteins/chemistry/*genetics/*metabolism ; Transcription, Genetic/genetics ; }, abstract = {Alternative splicing of pre-mRNA generates two or more protein isoforms from a single gene, thereby contributing to protein diversity. Despite intensive efforts, an understanding of the protein structure-function implications of alternative splicing is still lacking. Intrinsic disorder, which is a lack of equilibrium 3D structure under physiological conditions, may provide this understanding. Intrinsic disorder is a common phenomenon, particularly in multicellular eukaryotes, and is responsible for important protein functions including regulation and signaling. We hypothesize that polypeptide segments affected by alternative splicing are most often intrinsically disordered such that alternative splicing enables functional and regulatory diversity while avoiding structural complications. We analyzed a set of 46 differentially spliced genes encoding experimentally characterized human proteins containing both structured and intrinsically disordered amino acid segments. We show that 81% of 75 alternatively spliced fragments in these proteins were associated with fully (57%) or partially (24%) disordered protein regions. Regions affected by alternative splicing were significantly biased toward encoding disordered residues, with a vanishingly small P value. A larger data set composed of 558 SwissProt proteins with known isoforms produced by 1,266 alternatively spliced fragments was characterized by applying the pondr vsl1 disorder predictor. Results from prediction data are consistent with those obtained from experimental data, further supporting the proposed hypothesis. Associating alternative splicing with protein disorder enables the time- and tissue-specific modulation of protein function needed for cell differentiation and the evolution of multicellular organisms.}, } @article {pmid16707579, year = {2006}, author = {Short, MB and Solari, CA and Ganguly, S and Powers, TR and Kessler, JO and Goldstein, RE}, title = {Flows driven by flagella of multicellular organisms enhance long-range molecular transport.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, number = {22}, pages = {8315-8319}, pmid = {16707579}, issn = {0027-8424}, mesh = {Animals ; Biological Transport ; Cell Differentiation ; Chlamydomonas/cytology/*metabolism/physiology ; Chlorophyta/cytology/*metabolism/physiology ; Flagella/*physiology ; Motor Activity/*physiology ; }, abstract = {Evolution from unicellular organisms to larger multicellular ones requires matching their needs to the rate of exchange of molecular nutrients with the environment. This logistic problem poses a severe constraint on development. For organisms whose body plan is a spherical shell, such as the volvocine green algae, the current (molecules per second) of needed nutrients grows quadratically with radius, whereas the rate at which diffusion alone exchanges molecules grows linearly, leading to a bottleneck radius beyond which the diffusive current cannot meet metabolic demands. By using Volvox carteri, we examine the role that advection of fluid by the coordinated beating of surface-mounted flagella plays in enhancing nutrient uptake and show that it generates a boundary layer of concentration of the diffusing solute. That concentration gradient produces an exchange rate that is quadratic in the radius, as required, thus circumventing the bottleneck and facilitating evolutionary transitions to multicellularity and germ-soma differentiation in the volvocalean green algae.}, } @article {pmid16707573, year = {2006}, author = {Velicer, GJ and Raddatz, G and Keller, H and Deiss, S and Lanz, C and Dinkelacker, I and Schuster, SC}, title = {Comprehensive mutation identification in an evolved bacterial cooperator and its cheating ancestor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, number = {21}, pages = {8107-8112}, pmid = {16707573}, issn = {0027-8424}, mesh = {Adaptation, Biological ; DNA Mutational Analysis ; Evolution, Molecular ; Genome ; Genotype ; *Mutation ; Myxococcus xanthus/*genetics ; Probability ; *Sequence Analysis, DNA ; }, abstract = {Precise characterization of the mutation histories of evolutionary lineages is crucial for understanding the evolutionary process, yet mutation identification has been constrained by traditional techniques. We sought to identify all accumulated mutations in an experimentally evolved lineage of the cooperative bacterium Myxococcus xanthus, which constructs fruiting bodies by a process of social multicellular development in response to starvation. This lineage had undergone two major transitions in social phenotype: from an ancestral cooperator to a socially defective cheater, and from the cheater to a competitively dominant cooperator that re-evolved social and developmental proficiency. The 9.14-Mb genome of the evolved, dominant cooperator (strain "PX") was sequenced to approximately 19-fold coverage by using recent "sequencing-by-synthesis" technology and partially sequenced (approximately 45%) by using capillary technology. The resulting data revealed 15 single-nucleotide mutations relative to the laboratory ancestor of PX after the two phases of experimental evolution but no evidence of duplications, transpositions, or multiple-base deletions. No mutations were identified by capillary sequencing beyond those found by pyrosequencing, resulting in a high probability that all mutations were discovered. Seven errors in the reference strain previously sequenced by the Sanger approach were revealed, as were five mutational differences between two distinct laboratory stocks of the reference strain. A single mutation responsible for the restoration of development in strain PX was identified, whereas 14 mutations occurred during the prior phase of experimental evolution. These results provide insight into the genetic basis of two large adaptive transitions in a social bacterium.}, } @article {pmid16706173, year = {2005}, author = {Galitskiĭ, VA}, title = {[The origin of eukaryotic cells and origination of apoptosis].}, journal = {Tsitologiia}, volume = {47}, number = {2}, pages = {103-120}, pmid = {16706173}, issn = {0041-3771}, mesh = {Animals ; Apoptosis/*physiology ; *Biological Evolution ; Chloroplasts ; Cytoplasm/physiology ; Cytoskeleton ; Eukaryotic Cells/cytology/*physiology ; Intracellular Membranes/physiology ; Mitochondria/physiology ; Oncogene Proteins ; Prokaryotic Cells/physiology ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Signal Transduction ; Spindle Apparatus ; Symbiosis ; Tumor Suppressor Protein p53/metabolism ; Viral Proteins ; }, abstract = {The unified conception of the origin of eukaryotic cells has been proposed. In the author's opinion, evolutionary transformation of prokaryotic cell into eukaryotic cell took place 3.3-1.4 billion years ago and involved the next four stages: 1) the appearance of intracellular membranes due to prokaryotic cell plasmalemma invaginating into its cytoplasm; 2) the cell nucleus formation by the double sheet of intracellular membrane surrounding and sequestrating genetic material of the cell; 3) the appearance of cytoskeleton in parallel with mitotic spindle formation and gradual transition from prokaryotic way of cell division to mitosis; 4) the establishment of symbiosis between the evolving nucleated cell and prokaryotic microorganicsms that subsequently transform into mitochondria and chloroplasts. Apoptosis of cells of the present day multicellular eukaryotic organisms is supposed to be an evolutionary altered response of mitochondrian predecessors to the influence of factors, which are able to damage eukaryotic host cell. The initial biological significance of this reaction pertained to attempts of endosymbionts to leave the host cell as soon as possible, if the probability of its irreversible injury was very high, and by this to escape from their death. It is possible that numerous proteins, known as sensors or transducers of proapoptotic signals in Bcl-2--p53-dependent apoptotic pathway, were initially encoded by mitochondrial genome, whereas antiapoptotic factors and also components of receptor-mediated and granzyme B perforin dependent apoptotic pathways have cellular origin.}, } @article {pmid16702983, year = {2006}, author = {Khare, A and Shaulsky, G}, title = {First among equals: competition between genetically identical cells.}, journal = {Nature reviews. Genetics}, volume = {7}, number = {7}, pages = {577-583}, doi = {10.1038/nrg1875}, pmid = {16702983}, issn = {1471-0056}, mesh = {Animals ; Eukaryotic Cells/*cytology/*physiology ; *Evolution, Molecular ; *Genetic Variation ; Humans ; *Selection, Genetic ; }, abstract = {Competition between genetically identical organisms is considered insignificant in evolutionary theory because it is presumed to have little selective consequence. We argue that competition between genetically identical cells could improve the fitness of a multicellular organism by directing fitter cells to the germ line or by eliminating unfit cells, and that cell-competition mechanisms have been conserved in multicellular organisms. We propose that competition between genetically identical or highly similar units could have similar selective advantages at higher organizational levels, such as societies.}, } @article {pmid16700009, year = {2006}, author = {Redondo, C and Burke, BJ and Findlay, JB}, title = {The retinol-binding protein system: a potential paradigm for steroid-binding globulins?.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {38}, number = {4}, pages = {269-278}, doi = {10.1055/s-2006-925349}, pmid = {16700009}, issn = {0018-5043}, mesh = {Animals ; Animals, Genetically Modified ; Cattle ; Cell Line, Tumor ; Humans ; Mice ; Molecular Chaperones ; Protein Conformation ; Rabbits ; Rats ; Receptors, Cell Surface/metabolism ; Retinol-Binding Proteins/*metabolism ; Structure-Activity Relationship ; Vitamin A/blood ; }, abstract = {Retinol (vitamin A) is an example of a small molecule that is essential for higher organisms; its utilisation has been involved in the evolution of a number of proteins. In mammalian species, retinol is obtained from the diet and controls the release of its binding protein from hepatocytes into the blood stream. Subsequent influx into cells under normal situations usually involves a specific membrane-bound receptor for retinol-binding protein, which facilitates the uptake of retinol alone or bound to its carrier. This specific receptor has not yet been identified, but a receptor for a related lipocalin has been cloned. It represents a relatively new family, and there are a number of related genes in various eukaryotic genomes, suggesting that the system is very widespread in multicellular organisms. Its significance has been highlighted recently by the suggestion that retinol-binding protein, through its receptor, may play a major role in type 2 diabetes, perhaps the greatest scourge of modern society. This system may provide a new paradigm in mammalian biology, another example of which may exist in the processes responsible for steroid handling. This review outlines the characteristics of retinol utilisation in mammalian species, focusing primarily on the uptake system.}, } @article {pmid16699495, year = {2006}, author = {Cornillon, S and Gebbie, L and Benghezal, M and Nair, P and Keller, S and Wehrle-Haller, B and Charette, SJ and Brückert, F and Letourneur, F and Cosson, P}, title = {An adhesion molecule in free-living Dictyostelium amoebae with integrin beta features.}, journal = {EMBO reports}, volume = {7}, number = {6}, pages = {617-621}, pmid = {16699495}, issn = {1469-221X}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Cell Adhesion ; Cell Adhesion Molecules/*chemistry/genetics/*metabolism ; Cell Movement ; Conserved Sequence ; Cytosol/metabolism ; Dictyostelium/genetics ; Genes, Protozoan ; Glutathione Transferase/metabolism ; Integrins/*chemistry/genetics/*metabolism ; Molecular Sequence Data ; Mutation ; Protein Sorting Signals ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry/metabolism ; Recombination, Genetic ; Talin/metabolism ; }, abstract = {The study of free-living amoebae has proven valuable to explain the molecular mechanisms controlling phagocytosis, cell adhesion and motility. In this study, we identified a new adhesion molecule in Dictyostelium amoebae. The SibA (Similar to Integrin Beta) protein is a type I transmembrane protein, and its cytosolic, transmembrane and extracellular domains contain features also found in integrin beta chains. In addition, the conserved cytosolic domain of SibA interacts with talin, a well-characterized partner of mammalian integrins. Finally, genetic inactivation of SIBA affects adhesion to phagocytic particles, as well as cell adhesion and spreading on its substrate. It does not visibly alter the organization of the actin cytoskeleton, cellular migration or multicellular development. Our results indicate that the SibA protein is a Dictyostelium cell adhesion molecule presenting structural and functional similarities to metazoan integrin beta chains. This study sheds light on the molecular mechanisms controlling cell adhesion and their establishment during evolution.}, } @article {pmid16697247, year = {2006}, author = {Serna, L and Martin, C}, title = {Trichomes: different regulatory networks lead to convergent structures.}, journal = {Trends in plant science}, volume = {11}, number = {6}, pages = {274-280}, doi = {10.1016/j.tplants.2006.04.008}, pmid = {16697247}, issn = {1360-1385}, mesh = {Anthocyanins/biosynthesis ; Antirrhinum/genetics/growth & development ; Arabidopsis/genetics/*growth & development ; Arabidopsis Proteins ; Gossypium/genetics/growth & development ; Phylogeny ; Plant Proteins/*genetics ; Proto-Oncogene Proteins c-myb/*genetics ; Regulatory Elements, Transcriptional/*genetics/*physiology ; Solanaceae/genetics/growth & development ; }, abstract = {Sometimes, proteins, biological structures or even organisms have similar functions and appearances but have evolved through widely divergent pathways. There is experimental evidence to suggest that different developmental pathways have converged to produce similar outgrowths of the aerial plant epidermis, referred to as trichomes. The emerging picture suggests that trichomes in Arabidopsis thaliana and, perhaps, in cotton develop through a transcriptional regulatory network that differs from those regulating trichome formation in Antirrhinum and Solanaceous species. Several lines of evidence suggest that the duplication of a gene controlling anthocyanin production and subsequent divergence might be the major force driving trichome formation in Arabidopsis, whereas the multicellular trichomes of Antirrhinum and Solanaceous species appear to have a different regulatory origin.}, } @article {pmid16672510, year = {2006}, author = {Vos, M and Velicer, GJ}, title = {Genetic population structure of the soil bacterium Myxococcus xanthus at the centimeter scale.}, journal = {Applied and environmental microbiology}, volume = {72}, number = {5}, pages = {3615-3625}, pmid = {16672510}, issn = {0099-2240}, mesh = {Bacterial Proteins/genetics ; Bacterial Typing Techniques ; Evolution, Molecular ; *Genetic Variation ; Genotype ; Molecular Sequence Data ; Myxococcus xanthus/*classification/*genetics/growth & development/isolation & purification ; Phylogeny ; Polymorphism, Genetic ; Recombination, Genetic ; Selection, Genetic ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {Myxococcus xanthus is a gram-negative soil bacterium best known for its remarkable life history of social swarming, social predation, and multicellular fruiting body formation. Very little is known about genetic diversity within this species or how social strategies might vary among neighboring strains at small spatial scales. To investigate the small-scale population structure of M. xanthus, 78 clones were isolated from a patch of soil (16 by 16 cm) in Tübingen, Germany. Among these isolates, 21 genotypes could be distinguished from a concatemer of three gene fragments: csgA (developmental C signal), fibA (extracellular matrix-associated zinc metalloprotease), and pilA (the pilin subunit of type IV pili). Accumulation curves showed that most of the diversity present at this scale was sampled. The pilA gene contains both conserved and highly variable regions, and two frequency-distribution tests provide evidence for balancing selection on this gene. The functional domains in the csgA gene were found to be conserved. Three instances of lateral gene transfer could be inferred from a comparison of individual gene phylogenies, but no evidence was found for linkage equilibrium, supporting the view that M. xanthus evolution is largely clonal. This study shows that M. xanthus is surrounded by a variety of distinct conspecifics in its natural soil habitat at a spatial scale at which encounters among genotypes are likely.}, } @article {pmid16670996, year = {2006}, author = {Solari, CA and Kessler, JO and Michod, RE}, title = {A hydrodynamics approach to the evolution of multicellularity: flagellar motility and germ-soma differentiation in volvocalean green algae.}, journal = {The American naturalist}, volume = {167}, number = {4}, pages = {537-554}, doi = {10.1086/501031}, pmid = {16670996}, issn = {1537-5323}, mesh = {*Biological Evolution ; *Cell Differentiation ; Cell Movement ; Cell Size ; Chlorophyta/classification/*cytology ; Flagella/*physiology ; Germ Cells/*cytology ; Models, Biological ; Phylogeny ; Volvox/classification/cytology ; }, abstract = {During the unicellular-multicellular transition, there are opportunities and costs associated with larger size. We argue that germ-soma separation evolved to counteract the increasing costs and requirements of larger multicellular colonies. Volvocalean green algae are uniquely suited for studying this transition because they range from unicells to multicellular individuals with germ-soma separation. Because Volvocales need flagellar beating for movement and to avoid sinking, their motility is modeled and analyzed experimentally using standard hydrodynamics. We provide comparative hydrodynamic data of an algal lineage composed of organisms of different sizes and degrees of complexity. In agreement with and extending the insights of Koufopanou, we show that the increase in cell specialization as colony size increases can be explained in terms of increased motility requirements. First, as colony size increases, soma must evolve, the somatic-to-reproductive cell ratio increasing to keep colonies buoyant and motile. Second, increased germ-soma specialization in larger colonies increases motility capabilities because internalization of nonflagellated germ cells decreases colony drag. Third, our analysis yields a limiting maximum size of the volvocalean spheroid that agrees with the sizes of the largest species known. Finally, the different colony designs in Volvocales reflect the trade-offs between reproduction, colony size, and motility.}, } @article {pmid16650748, year = {2006}, author = {DePamphilis, ML and Blow, JJ and Ghosh, S and Saha, T and Noguchi, K and Vassilev, A}, title = {Regulating the licensing of DNA replication origins in metazoa.}, journal = {Current opinion in cell biology}, volume = {18}, number = {3}, pages = {231-239}, doi = {10.1016/j.ceb.2006.04.001}, pmid = {16650748}, issn = {0955-0674}, support = {A3135/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Cell Cycle ; Cell Cycle Proteins/metabolism ; Cell Division ; DNA Helicases/metabolism ; *DNA Replication ; Humans ; Models, Genetic ; Origin Recognition Complex/metabolism ; Plants/genetics ; Replication Origin ; }, abstract = {Eukaryotic DNA replication is a highly conserved process; the proteins and sequence of events that replicate animal genomes are remarkably similar to those that replicate yeast genomes. Moreover, the assembly of prereplication complexes at DNA replication origins ('DNA licensing') is regulated in all eukaryotes so that no origin fires more than once in a single cell cycle. And yet there are significant differences between species both in the selection of replication origins and in the way in which these origins are licensed to operate. Moreover, these differences impart advantages to multicellular animals and plants that facilitate their development, such as better control over endoreduplication, flexibility in origin selection, and discrimination between quiescent and proliferative states.}, } @article {pmid16647825, year = {2006}, author = {Pugacheva, EM and Kwon, YW and Hukriede, NA and Pack, S and Flanagan, PT and Ahn, JC and Park, JA and Choi, KS and Kim, KW and Loukinov, D and Dawid, IB and Lobanenkov, VV}, title = {Cloning and characterization of zebrafish CTCF: Developmental expression patterns, regulation of the promoter region, and evolutionary aspects of gene organization.}, journal = {Gene}, volume = {375}, number = {}, pages = {26-36}, doi = {10.1016/j.gene.2006.01.036}, pmid = {16647825}, issn = {0378-1119}, support = {//Intramural NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; CCCTC-Binding Factor ; Cloning, Molecular ; DNA Primers ; DNA-Binding Proteins/*genetics ; *Evolution, Molecular ; Humans ; In Situ Hybridization ; Molecular Sequence Data ; Plasmids ; *Promoter Regions, Genetic ; Repressor Proteins/*genetics ; Sequence Homology, Amino Acid ; Transcription, Genetic ; Zebrafish/*genetics ; }, abstract = {CTCF is a nuclear phosphoprotein capable of using different subsets of its 11 Zn fingers (ZF) for sequence-specific binding to many dissimilar DNA CTCF-target sites. Such sites were identified in the genomic DNA of various multicellular organisms, in which the CTCF gene was cloned, including insects, birds, rodents, and primates. CTCF/DNA-complexes formed in vivo with different 50-bp-long sequences mediate diverse functions such as positive and negative regulation of promoters, and organization of all known enhancer-blocking elements ("chromatin insulators") including constitutive and epigenetically regulated elements. Abnormal functions of certain CTCF sites are implicated in cancer and in epigenetic syndromes such as BWS and skewed X-inactivation. We describe here the cloning and characterization of the CTCF cDNA and promoter region from zebrafish, a valuable vertebrate model organism. The full-length zebrafish CTCF cDNA clone is 4244 bp in length with an open reading frame (ORF) of 2391 bp that encodes 797 amino acids. The zebrafish CTCF amino acid sequence shows high identity (up to 98% in the zinc finger region) with human CTCF, and perfect conservation of exon-intron organization. Southern blot analyses indicated that the zebrafish genome contains a single copy of the CTCF gene. In situ hybridization revealed the presence of zebrafish CTCF transcripts in all early stages of embryogenesis. Transfection assays with luciferase reporter-constructs identified a core promoter region within 146 bp immediately upstream of the transcriptional start site of zebrafish CTCF that is located at a highly conserved YY1/Initiator element.}, } @article {pmid16647180, year = {2006}, author = {Wu, Q and Gu, X and Wang, Y and Li, N and Liu, X and Wu, C and Yu, L and Gu, X}, title = {Neurotransmitter inactivation is important for the origin of nerve system in animal early evolution: a suggestion from genomic comparison.}, journal = {Progress in neurobiology}, volume = {78}, number = {6}, pages = {390-395}, doi = {10.1016/j.pneurobio.2006.03.002}, pmid = {16647180}, issn = {0301-0082}, mesh = {Animals ; *Biological Evolution ; Genomics ; Humans ; Neurotransmitter Agents/*genetics/*metabolism ; *Phylogeny ; Synapses/metabolism ; Synaptic Transmission/genetics ; }, abstract = {Metazoans possess complicated multicellular structure among the multicellularities of eukaryotes. One evolutionary pressure that permits such complexity relates to the directed and precise informational transmission performed by numerous synapses in neuron system. Neurotransmitter inactivations play essential roles in the termination of synaptic transmission and are thus crucial for precise synaptic transmission. Here, we performed a genomic comparison among 11 eukaryotic organisms including five bilaterian species and six pan-unicellular eukaryotes to search for genes related to metazoan multicellular function. The result showed that the majority of genes related to neurotransmitter inactivation in the synaptic cleft endured high and stable selective pressure and were specifically present in bilaterians, whereas genes related to transmitter release and postsynaptic transmitter receptors did not show these properties. From these data we conclude that neurotransmitter inaction may play a critical role in the origin of the nerve system encountered in the early evolution of metazoan. In addition, we suggest that neurotransmitter inactivation probably participates in the formation or refinement of the synapse, following the concept of "ontogeny recapitulates phylogeny." Further experimental evidence is needed to support the suggestion and to explain the importance of neurotransmitter inactivation to metazoan multicellular function.}, } @article {pmid16643865, year = {2006}, author = {Fritzsch, B and Pauley, S and Beisel, KW}, title = {Cells, molecules and morphogenesis: the making of the vertebrate ear.}, journal = {Brain research}, volume = {1091}, number = {1}, pages = {151-171}, pmid = {16643865}, issn = {0006-8993}, support = {1 C06 RR17417-01/RR/NCRR NIH HHS/United States ; DC005590/DC/NIDCD NIH HHS/United States ; R01 DC005590-05/DC/NIDCD NIH HHS/United States ; C06 RR017417/RR/NCRR NIH HHS/United States ; R01 DC005590/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Ear/*physiology ; *Gene Expression Regulation, Developmental ; Humans ; Mechanoreceptors/*physiology ; Morphogenesis/*physiology ; Vertebrates ; }, abstract = {The development and evolution of mechanosensory cells and the vertebrate ear is reviewed with an emphasis on delineating the cellular, molecular and developmental basis of these changes. Outgroup comparisons suggests that mechanosensory cells are ancient features of multicellular organisms. Molecular evidence suggests that key genes involved in mechanosensory cell function and development are also conserved among metazoans. The divergent morphology of mechanosensory cells across phyla is interpreted here as 'deep molecular homology' that was in parallel shaped into different forms in each lineage. The vertebrate mechanosensory hair cell and its associated neuron are interpreted as uniquely derived features of vertebrates. It is proposed that the vertebrate otic placode presents a unique embryonic adaptation in which the diffusely distributed ancestral mechanosensory cells became concentrated to generate a large neurosensory precursor population. Morphogenesis of the inner ear is reviewed and shown to depend on genes expressed in and around the hindbrain that interact with the otic placode to define boundaries and polarities. These patterning genes affect downstream genes needed to maintain proliferation and to execute ear morphogenesis. We propose that fibroblast growth factors (FGFs) and their receptors (FGFRs) are a crucial central node to translate patterning into the complex morphology of the vertebrate ear. Unfortunately, the FGF and FGFR genes have not been fully analyzed in the many mutants with morphogenetic ear defects described thus far. Likewise, little information exists on the ear histogenesis and neurogenesis in many mutants. Nevertheless, a molecular mechanism is now emerging for the formation of the horizontal canal, an evolutionary novelty of the gnathostome ear. The existing general module mediating vertical canal growth and morphogenesis was modified by two sets of new genes: one set responsible for horizontal canal morphogenesis and another set for neurosensory formation of the horizontal crista and associated sensory neurons. The dramatic progress in deciphering the molecular basis of ear morphogenesis offers grounds for optimism for translational research toward intervention in human morphogenetic defects of the ear.}, } @article {pmid16638569, year = {2006}, author = {Margis, R and Fusaro, AF and Smith, NA and Curtin, SJ and Watson, JM and Finnegan, EJ and Waterhouse, PM}, title = {The evolution and diversification of Dicers in plants.}, journal = {FEBS letters}, volume = {580}, number = {10}, pages = {2442-2450}, doi = {10.1016/j.febslet.2006.03.072}, pmid = {16638569}, issn = {0014-5793}, mesh = {Arabidopsis/*genetics ; Arabidopsis Proteins/*genetics ; *Evolution, Molecular ; Genes, Plant ; Oryza/*genetics ; Populus/*genetics ; Species Specificity ; }, abstract = {Most multicellular organisms regulate developmental transitions by microRNAs, which are generated by an enzyme, Dicer. Insects and fungi have two Dicer-like genes, and many animals have only one, yet the plant, Arabidopsis, has four. Examining the poplar and rice genomes revealed that they contain five and six Dicer-like genes, respectively. Analysis of these genes suggests that plants require a basic set of four Dicer types which were present before the divergence of mono- and dicotyledonous plants (approximately 200 million years ago), but after the divergence of plants from green algae. A fifth type of Dicer seems to have evolved in monocots.}, } @article {pmid16623698, year = {2006}, author = {Jun, SH and Kim, TG and Ban, C}, title = {DNA mismatch repair system. Classical and fresh roles.}, journal = {The FEBS journal}, volume = {273}, number = {8}, pages = {1609-1619}, doi = {10.1111/j.1742-4658.2006.05190.x}, pmid = {16623698}, issn = {1742-464X}, mesh = {Animals ; *Base Pair Mismatch ; DNA Damage ; *DNA Repair ; DNA Repair Enzymes ; Humans ; MutL Proteins ; MutS DNA Mismatch-Binding Protein/physiology ; Neoplasm Proteins/physiology ; Proteins/*physiology ; }, abstract = {The molecular mechanisms of the DNA mismatch repair (MMR) system have been uncovered over the last decade, especially in prokaryotes. The results obtained for prokaryotic MMR proteins have provided a framework for the study of the MMR system in eukaryotic organisms, such as yeast, mouse and human, because the functions of MMR proteins have been conserved during evolution from bacteria to humans. However, mutations in eukaryotic MMR genes result in pleiotropic phenotypes in addition to MMR defects, suggesting that eukaryotic MMR proteins have evolved to gain more diverse and specific roles in multicellular organisms. Here, we summarize recent advances in the understanding of both prokaryotic and eukaryotic MMR systems and describe various new functions of MMR proteins that have been intensively researched during the last few years, including DNA damage surveillance and diversification of antibodies.}, } @article {pmid16619242, year = {2006}, author = {Danilova, N}, title = {The evolution of immune mechanisms.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {306}, number = {6}, pages = {496-520}, doi = {10.1002/jez.b.21102}, pmid = {16619242}, issn = {1552-5007}, mesh = {Adaptation, Biological/*immunology ; Antimicrobial Cationic Peptides/immunology ; Apoptosis/immunology ; *Biological Evolution ; Complement System Proteins/immunology ; Immunity/*genetics/*immunology ; Phagocytosis/immunology ; RNA Interference ; Receptor Cross-Talk/immunology ; }, abstract = {From early on in evolution, organisms have had to protect themselves from pathogens. Mechanisms for discriminating "self" from "non-self" evolved to accomplish this task, launching a long history of host-pathogen co-evolution. Evolution of mechanisms of immune defense has resulted in a variety of strategies. Even unicellular organisms have rich arsenals of mechanisms for protection, such as restriction endonucleases, antimicrobial peptides, and RNA interference. In multicellular organisms, specialized immune cells have evolved, capable of recognition, phagocytosis, and killing of foreign cells as well as removing their own cells changed by damage, senescence, infection, or cancer. Additional humoral factors, such as the complement cascade, have developed that co-operate with cellular immunity in fighting infection and maintaining homeostasis. Defensive mechanisms based on germline-encoded receptors constitute a system known as innate immunity. In jaw vertebrates, this system is supplemented with a second system, adaptive immunity, which in contrast to innate immunity is based on diversification of immune receptors and on immunological memory in each individual.Usually, each newly evolved defense mechanism did not replace the previous one, but supplemented it, resulting in a layered structure of the immune system. The immune system is not one system but rather a sophisticated network of various defensive mechanisms operating on different levels, ranging from mechanisms common for every cell in the body to specialized immune cells and responses at the level of the whole organism. Adaptive changes in pathogens have shaped the evolution of the immune system at all levels.}, } @article {pmid16615205, year = {2006}, author = {Snell, EA and Brooke, NM and Taylor, WR and Casane, D and Philippe, H and Holland, PW}, title = {An unusual choanoflagellate protein released by Hedgehog autocatalytic processing.}, journal = {Proceedings. Biological sciences}, volume = {273}, number = {1585}, pages = {401-407}, pmid = {16615205}, issn = {0962-8452}, support = {MC_U117581331/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; DNA, Protozoan/chemistry/genetics ; Eukaryotic Cells/*metabolism/physiology ; Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Proteins/genetics/*metabolism ; Random Amplified Polymorphic DNA Technique ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {Hedgehog proteins are important cell-cell signalling proteins utilized during the development of multicellular animals. Members of the hedgehog gene family have not been detected outside the Metazoa, raising unanswered questions about their evolutionary origin. Here we report a highly unusual hedgehog-related gene from a choanoflagellate, a close unicellular relative of the animals. The deduced C-terminal domain, Hoglet-C, is homologous to the autocatalytic domain of Hedgehog proteins and is predicted to function in autocatalytic cleavage of the precursor peptide. In contrast, the N-terminal Hoglet-N peptide has no similarity to the signalling peptide of Hedgehog (Hh-N). Instead, Hoglet-N is deduced to be a secreted protein with an enormous threonine-rich domain of unprecedented size and purity (over 200 threonine residues) and two polysaccharide-binding domains. Structural modelling reveals that these domains have a novel combination of features found in cellulose-binding domains (CBD) of types IIa and IIb, and are expected to bind cellulose. We propose that the two CBD domains enable Hoglet-N to bind to plant matter, tethering an amorphous nucleophilic anchor, facilitating transient adhesion of the choanoflagellate cell. Since Hh-C and Hoglet-C are homologous, but Hh-N and Hoglet-N are not, we argue that metazoan hedgehog genes evolved by fusion of two distinct genes.}, } @article {pmid16612891, year = {2006}, author = {Haig, D and Wilczek, A}, title = {Sexual conflict and the alternation of haploid and diploid generations.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {361}, number = {1466}, pages = {335-343}, pmid = {16612891}, issn = {0962-8436}, mesh = {Bryophyta/*genetics ; Chlorophyta/*genetics ; *Diploidy ; Ferns/*genetics ; *Haploidy ; Reproduction/genetics ; }, abstract = {Land plants possess a multicellular diploid stage (sporophyte) that begins development while attached to a multicellular haploid progenitor (gametophyte). Although the closest algal relatives of land plants lack a multicellular sporophyte, they do produce a zygote that grows while attached to the maternal gametophyte. The diploid offspring shares one haploid set of genes with the haploid mother that supplies it with resources and a paternal haploid complement that is not shared with the mother. Sexual conflict can arise within the diploid offspring because the offspring's maternal genome will be transmitted in its entirety to all other sexual and asexual offspring that the mother may produce, but the offspring's paternally derived genes may be absent from these other offspring. Thus, the selective forces favouring the evolution of genomic imprinting may have been present from the origin of modern land plants. In bryophytes, where gametophytes are long-lived and capable of multiple bouts of asexual and sexual reproduction, we predict strong sexual conflict over allocation to sporophytes. Female gametophytes of pteridophytes produce a single sporophyte and often lack means of asexual reproduction. Therefore, sexual conflict is predicted to be attenuated. Finally, we explore similarities among models of mate choice, offspring choice and segregation distortion.}, } @article {pmid16612382, year = {2006}, author = {Kupfer, A and Müller, H and Antoniazzi, MM and Jared, C and Greven, H and Nussbaum, RA and Wilkinson, M}, title = {Parental investment by skin feeding in a caecilian amphibian.}, journal = {Nature}, volume = {440}, number = {7086}, pages = {926-929}, doi = {10.1038/nature04403}, pmid = {16612382}, issn = {1476-4687}, mesh = {Amphibians/*anatomy & histology/growth & development/*physiology ; *Animal Nutritional Physiological Phenomena ; Animals ; Eating/*physiology ; Female ; *Mothers ; Oviparity/physiology ; Selection, Genetic ; *Skin/anatomy & histology/cytology ; Tooth/anatomy & histology/physiology ; }, abstract = {Although the initial growth and development of most multicellular animals depends on the provision of yolk, there are many varied contrivances by which animals provide additional or alternative investment in their offspring. Providing offspring with additional nutrition should be favoured by natural selection when the consequent increased fitness of the young offsets any corresponding reduction in fecundity. Alternative forms of nutrition may allow parents to delay and potentially redirect their investment. Here we report a remarkable form of parental care and mechanism of parent-offspring nutrient transfer in a caecilian amphibian. Boulengerula taitanus is a direct-developing, oviparous caecilian, the skin of which is transformed in brooding females to provide a rich supply of nutrients for the developing offspring. Young animals are equipped with a specialized dentition, which they use to peel and eat the outer layer of their mother's modified skin. This new form of parental care provides a plausible intermediate stage in the evolution of viviparity in caecilians. At independence, offspring of viviparous and of oviparous dermatotrophic caecilians are relatively large despite being provided with relatively little yolk. The specialized dentition of skin-feeding (dermatophagous) caecilians may constitute a preadaptation to the fetal feeding on the oviduct lining of viviparous caecilians.}, } @article {pmid16600526, year = {2006}, author = {Ermolenko, AE and Perepada, EA}, title = {Origin of segmentation in the human structure.}, journal = {Medical hypotheses}, volume = {67}, number = {3}, pages = {622-625}, doi = {10.1016/j.mehy.2006.02.030}, pmid = {16600526}, issn = {0306-9877}, mesh = {*Biological Evolution ; Body Patterning/*physiology ; Humans ; Models, Biological ; Viscera/*anatomy & histology/embryology/*physiology ; }, abstract = {Crystallographic analysis of biological and non-biological minerals does not reveal any significant differences between the two, which is indicative of common crystallization processes. It can be supposed that the human organism is a biocrystalloid in a sense that it is regarded both at the level of the whole organism and individual cells as a composite entity consisting of a crystal-like structure and pericrystalline medium. A similarity can be found between the growing layer of a crystal in the crystal-forming medium and a cell structure with liquid washing it. A mineral organism therefore can be regarded as the active superficial part of a crystal taken together with pericrystalline crystal-forming medium which controls crystal growth and modifies the system depending on the structure of the growing system. Aggregation is one of the fundamental features of minerals as they are found primarily not only as separate objects but also as aggregates, i.e. regular cohesive masses or synmineralogical systems. Ability to aggregation in an orderly way is expressed as self-organization. This feature is inherent not only to compound molecules but also to associates of a higher order. The cell biology has shown that when similar cells touch each other they tend to cohere forming aggregates characteristic of the given cell population. Similar live systems and their components that perform the same function have an ability to integrate and form firstly a conglomerate (colony) and then an organism. Integration explains association of multi-segmented entities into a single organism and the resulting structure would consists of the two groups of segments, i.e. appearance of an organism consisting of two different but of the same type specimens, each of which had different number of segments. Phylogenetically, an early precursor of the man evolved from a simple cell into an integrated multi-segment organism through several stages--initially a simple cell, then a cell colony, then a single-segment organism, then an organism like a concave ball, then a colony of one-segment multicellular organisms and finally a multi-segment multicellular organism. Integration of five- and eight-segment organisms resulted in the formation of a 13-segment precursor organism of man. Segmentation is nothing else but traces of boundaries left following integration of separate multicellular non-segmented specimens with gradual fading of their differences and formation of a new entity in compliance with formation laws.}, } @article {pmid16600051, year = {2006}, author = {Vinogradov, SN and Hoogewijs, D and Bailly, X and Arredondo-Peter, R and Gough, J and Dewilde, S and Moens, L and Vanfleteren, JR}, title = {A phylogenomic profile of globins.}, journal = {BMC evolutionary biology}, volume = {6}, number = {}, pages = {31}, pmid = {16600051}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Genes, Archaeal ; Genes, Bacterial ; Genes, Fungal ; Genes, Helminth ; Genes, Insect ; Genes, Plant ; Genome ; Globins/classification/*genetics ; Humans ; Molecular Sequence Data ; *Phylogeny ; Sequence Alignment ; Sequence Homology, Amino Acid ; Species Specificity ; Truncated Hemoglobins ; Vertebrates/genetics ; }, abstract = {BACKGROUND: Globins occur in all three kingdoms of life: they can be classified into single-domain globins and chimeric globins. The latter comprise the flavohemoglobins with a C-terminal FAD-binding domain and the gene-regulating globin coupled sensors, with variable C-terminal domains. The single-domain globins encompass sequences related to chimeric globins and "truncated" hemoglobins with a 2-over-2 instead of the canonical 3-over-3 alpha-helical fold.

RESULTS: A census of globins in 26 archaeal, 245 bacterial and 49 eukaryote genomes was carried out. Only approximately 25% of archaea have globins, including globin coupled sensors, related single domain globins and 2-over-2 globins. From one to seven globins per genome were found in approximately 65% of the bacterial genomes: the presence and number of globins are positively correlated with genome size. Globins appear to be mostly absent in Bacteroidetes/Chlorobi, Chlamydia, Lactobacillales, Mollicutes, Rickettsiales, Pastorellales and Spirochaetes. Single domain globins occur in metazoans and flavohemoglobins are found in fungi, diplomonads and mycetozoans. Although red algae have single domain globins, including 2-over-2 globins, the green algae and ciliates have only 2-over-2 globins. Plants have symbiotic and nonsymbiotic single domain hemoglobins and 2-over-2 hemoglobins. Over 90% of eukaryotes have globins: the nematode Caenorhabditis has the most putative globins, approximately 33. No globins occur in the parasitic, unicellular eukaryotes such as Encephalitozoon, Entamoeba, Plasmodium and Trypanosoma.

CONCLUSION: Although Bacteria have all three types of globins, Archaeado not have flavohemoglobins and Eukaryotes lack globin coupled sensors. Since the hemoglobins in organisms other than animals are enzymes or sensors, it is likely that the evolution of an oxygen transport function accompanied the emergence of multicellular animals.}, } @article {pmid16596704, year = {2006}, author = {McCarthy, FM and Cooksey, AM and Wang, N and Bridges, SM and Pharr, GT and Burgess, SC}, title = {Modeling a whole organ using proteomics: the avian bursa of Fabricius.}, journal = {Proteomics}, volume = {6}, number = {9}, pages = {2759-2771}, doi = {10.1002/pmic.200500648}, pmid = {16596704}, issn = {1615-9853}, mesh = {Amino Acid Sequence ; Animals ; *Bursa of Fabricius ; Cells, Cultured ; Chickens ; *Databases, Genetic ; Humans ; *Models, Biological ; Molecular Sequence Data ; Phylogeny ; *Proteomics ; Sequence Alignment ; }, abstract = {While advances in proteomics have improved proteome coverage and enhanced biological modeling, modeling function in multicellular organisms requires understanding how cells interact. Here we used the chicken bursa of Fabricius, a common experimental system for B cell function, to model organ function from proteomics data. The bursa has two major functional cell types: B cells and the supporting stromal cells. We used differential detergent fractionation-multidimensional protein identification technology (DDF-MudPIT) to identify 5198 proteins from all cellular compartments. Of these, 1753 were B cell specific, 1972 were stroma specific and 1473 were shared between the two. By modeling programmed cell death (PCD), cell differentiation and proliferation, and transcriptional activation, we have improved functional annotation of chicken proteins and placed chicken-specific death receptors into the PCD process using phylogenetics. We have identified 114 transcription factors (TFs); 42 of the bursal B cell TFs have not been reported before in any B cells. We have also improved the structural annotation of a newly sequenced genome by confirming the in vivo expression of 4006 "predicted", and 6623 ab initio, ORFs. Finally, we have developed a novel method for facilitating structural annotation, "expressed peptide sequence tags" (ePSTs) and demonstrate its utility by identifying 521 potential novel proteins from the chicken "unassigned chromosome".}, } @article {pmid16596165, year = {2006}, author = {Goldberg, JM and Manning, G and Liu, A and Fey, P and Pilcher, KE and Xu, Y and Smith, JL}, title = {The dictyostelium kinome--analysis of the protein kinases from a simple model organism.}, journal = {PLoS genetics}, volume = {2}, number = {3}, pages = {e38}, pmid = {16596165}, issn = {1553-7404}, mesh = {Amino Acid Sequence ; Animals ; Dictyostelium/*genetics ; Evolution, Molecular ; Expressed Sequence Tags ; Molecular Sequence Data ; Protein Kinases/*genetics/metabolism ; Sequence Alignment ; Sequence Analysis, Protein/*methods ; Signal Transduction ; }, abstract = {Dictyostelium discoideum is a widely studied model organism with both unicellular and multicellular forms in its developmental cycle. The Dictyostelium genome encodes 285 predicted protein kinases, similar to the count of the much more advanced Drosophila. It contains members of most kinase classes shared by fungi and metazoans, as well as many previously thought to be metazoan specific, indicating that they have been secondarily lost from the fungal lineage. This includes the entire tyrosine kinase-like (TKL) group, which is expanded in Dictyostelium and includes several novel receptor kinases. Dictyostelium lacks tyrosine kinase group kinases, and most tyrosine phosphorylation appears to be mediated by TKL kinases. About half of Dictyostelium kinases occur in subfamilies not present in yeast or metazoa, suggesting that protein kinases have played key roles in the adaptation of Dictyostelium to its habitat. This study offers insights into kinase evolution and provides a focus for signaling analysis in this system.}, } @article {pmid16582627, year = {2006}, author = {Gottfried, E and Kunz-Schughart, LA and Andreesen, R and Kreutz, M}, title = {Brave little world: spheroids as an in vitro model to study tumor-immune-cell interactions.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {5}, number = {7}, pages = {691-695}, doi = {10.4161/cc.5.7.2624}, pmid = {16582627}, issn = {1551-4005}, mesh = {Cell Culture Techniques/*methods ; Humans ; Immunity/*immunology ; Models, Biological ; Neoplasms/*immunology/pathology ; Spheroids, Cellular/*immunology/metabolism/*pathology ; Tumor Cells, Cultured ; }, abstract = {Multicellular tumor spheroids (MCTS) are a well-established 3-D in vitro model system that reflects the pathophysiological in vivo situation in tumor microregions and of avascular micrometastatic sites. Because monocytes and other immune cells infiltrate into MCTS of different origin, such spheroid cocultures are a valuable, still underestimated tool to systematically study heterologous interactions between tumor and immune cells. The present article gives a brief overview on work that has been published on tumor-immune cell interactions in MCTS and also summarizes mechanisms of immune suppression in the tumor milieu focussing on myeloid cells. Using the coculture model, we recently demonstrated that tumor-derived lactic acid is a potent modulator of human monocyte as lactic acid inhibited the differentiation of monocytes (MO) into dendritic cells (DC) and also impaired antigen presentation. We show herein, that the capacity of various tumor cells in MCTS to secrete lactic acid differs up to tenfold, suggesting that this capacity is dependent on the tumor cell type. It is further demonstrated that lactic acid disturbs the migration of MO into MCTS as infiltration could be increased by blocking lactic acid production. We therefore discuss lactic acid which accumulates in many tumors and tumor microregions as a potent immune suppressor for MO/DC in the tumor milieu and conclude that these data are highly relevant for adoptive immunotherapy protocols with DC.}, } @article {pmid16569691, year = {2006}, author = {Salipante, SJ and Horwitz, MS}, title = {Phylogenetic fate mapping.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, number = {14}, pages = {5448-5453}, pmid = {16569691}, issn = {0027-8424}, support = {R01 DK058161/DK/NIDDK NIH HHS/United States ; T32 GM007266/GM/NIGMS NIH HHS/United States ; R01 DK 58161/DK/NIDDK NIH HHS/United States ; T32 GM 007266/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Cell Lineage ; Female ; Genotype ; Mice ; NIH 3T3 Cells ; *Phylogeny ; }, abstract = {Cell fate maps describe how the sequence of cell division, migration, and apoptosis transform a zygote into an adult. Yet, it is only in Caenorhabditis elegans where microscopic observation of each cell division has allowed for construction of a complete fate map. More complex, and opaque, animals prove less yielding. DNA replication, however, generates somatic mutations. Consequently, multicellular organisms comprise mosaics where most cells acquire unique genomes that are potentially capable of delineating their ancestry. Here we take a phylogenetic approach to passively retrace embryonic relationships by deducing the order in which mutations have arisen during development. We show that polyguanine repeat DNA sequences are particularly useful genetic markers, because they frequently change length during mitosis. To demonstrate feasibility, we phylogenetically reconstruct the lineage of cultured mouse NIH 3T3 cells based on mutations affecting the length of polyguanine markers. We then employ whole genome amplification to genotype polyguanine markers in single cells taken from a mouse and use phylogenetics to infer the developmental relationships of the sampled tissues. The result is consistent with the present understanding of embryogenesis and demonstrates the large scale potential of this method for producing a complete mammalian cell fate at the resolution of a single cell.}, } @article {pmid16565042, year = {2006}, author = {Zeng, D and Ferrari, A and Ulmer, J and Veligodskiy, A and Fischer, P and Spatz, J and Ventikos, Y and Poulikakos, D and Kroschewski, R}, title = {Three-dimensional modeling of mechanical forces in the extracellular matrix during epithelial lumen formation.}, journal = {Biophysical journal}, volume = {90}, number = {12}, pages = {4380-4391}, pmid = {16565042}, issn = {0006-3495}, mesh = {Animals ; Cell Line ; Collagen Type I/*physiology/ultrastructure ; Computer Simulation ; Dogs ; Elasticity ; Epithelial Cells/*physiology/ultrastructure ; Extracellular Matrix/*physiology/ultrastructure ; Image Interpretation, Computer-Assisted/methods ; Imaging, Three-Dimensional/methods ; Kidney/*physiology/ultrastructure ; Mechanotransduction, Cellular/*physiology ; *Models, Biological ; Stress, Mechanical ; }, abstract = {Mechanical interactions between cells and extracellular matrix (ECM) mediate epithelial cyst formation. This work relies on the combination of numerical modeling with live cell imaging, to piece together a novel nonintrusive method for determining three-dimensional (3D) mechanical forces caused by shape changes of a multicellular aggregate at the early stages of epithelial cyst formation. We analyzed the evolution of Madin-Darby canine kidney cells in 3D cultures using time-lapse microscopy, with type I collagen gel forming the ECM. The evolving 3D interface between the ECM and the cell aggregate was obtained from microscopy images, and the stress on the surface of a proliferating aggregate and in the surrounding ECM was calculated using the finite element method. The viscoelastic properties of the ECM (a needed input for the finite element method solver) were obtained through oscillatory shear flow experiments on a rheometer. For validation purpose, the forces exerted by an aggregate on a force-sensor array were measured and compared against the computational results.}, } @article {pmid16556832, year = {2006}, author = {Lynch, M and Koskella, B and Schaack, S}, title = {Mutation pressure and the evolution of organelle genomic architecture.}, journal = {Science (New York, N.Y.)}, volume = {311}, number = {5768}, pages = {1727-1730}, doi = {10.1126/science.1118884}, pmid = {16556832}, issn = {1095-9203}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Chloroplasts/genetics ; DNA, Intergenic ; *Evolution, Molecular ; *Genes, Mitochondrial ; *Genetic Drift ; *Genome ; Genome, Plant ; Humans ; Mitochondria/*genetics ; *Mutation ; Phylogeny ; Plants/*genetics ; RNA Editing ; }, abstract = {The nuclear genomes of multicellular animals and plants contain large amounts of noncoding DNA, the disadvantages of which can be too weak to be effectively countered by selection in lineages with reduced effective population sizes. In contrast, the organelle genomes of these two lineages evolved to opposite ends of the spectrum of genomic complexity, despite similar effective population sizes. This pattern and other puzzling aspects of organelle evolution appear to be consequences of differences in organelle mutation rates. These observations provide support for the hypothesis that the fundamental features of genome evolution are largely defined by the relative power of two nonadaptive forces: random genetic drift and mutation pressure.}, } @article {pmid16555795, year = {2006}, author = {Perron, GG and Zasloff, M and Bell, G}, title = {Experimental evolution of resistance to an antimicrobial peptide.}, journal = {Proceedings. Biological sciences}, volume = {273}, number = {1583}, pages = {251-256}, pmid = {16555795}, issn = {0962-8452}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Antimicrobial Cationic Peptides/*pharmacology ; *Directed Molecular Evolution ; *Drug Resistance, Bacterial ; Escherichia coli/*drug effects/genetics ; Pseudomonas fluorescens/*drug effects/genetics ; }, abstract = {A novel class of antibiotics based on the antimicrobial properties of immune peptides of multicellular organisms is attracting increasing interest as a major weapon against resistant microbes. It has been claimed that cationic antimicrobial peptides exploit fundamental features of the bacterial cell so that resistance is much less likely to evolve than in the case of conventional antibiotics. Population models of the evolutionary genetics of resistance have cast doubt on this claim. We document the experimental evolution of resistance to a cationic antimicrobial peptide through continued selection in the laboratory. In this selection experiment, 22/24 lineages of Escherichia coli and Pseudomonas fluorescens independently evolved heritable mechanisms of resistance to pexiganan, an analogue of magainin, when propagated in medium supplemented with this antimicrobial peptide for 600-700 generations.}, } @article {pmid16555065, year = {2006}, author = {Biswas, PK and Niu, J and Frederico, T and Gogonea, V}, title = {Numerical simulation and graphical analysis of in vitro benign tumor growth: application of single-particle state bosonic matter equation with length scaling.}, journal = {Journal of molecular modeling}, volume = {12}, number = {5}, pages = {641-648}, pmid = {16555065}, issn = {0948-5023}, mesh = {Cell Proliferation ; Computer Simulation ; Neoplasms/*pathology ; }, abstract = {We describe the application of a non-linear single-particle state bosonic condensate equation to simulate multicellular tumor growth by treating it as a coupling of two classical wave equations with real components. With one component representing the amplitude of the cells in their volume growth phase and the other representing the amplitude of the cells in their proliferation or mitosis phase, the two components of the coupled equation feed each other during the time evolution and are coupled together through diffusion and other linear and non-linear terms. The features of quiescent and necrotic cells, which result from poor nutrient diffusion into a tumor, have been found to correspond quite well to experimental data when they are modeled as depending on higher cell density. Classical hallmarks of benign tumor growth, such as the initial rapid growth, followed by a dramatic collapse in the proliferating cell count and a strong re-growth thereafter appear quite encouragingly in the theoretical results. A tool for graphical analysis of the tumor simulation results has been developed to provide morphological information about tumors at various growth stages. The model and the graphical analysis can be extended further to create an effective tool to predict/monitor tumor growth.}, } @article {pmid16531491, year = {2006}, author = {Cnops, G and Neyt, P and Raes, J and Petrarulo, M and Nelissen, H and Malenica, N and Luschnig, C and Tietz, O and Ditengou, F and Palme, K and Azmi, A and Prinsen, E and Van Lijsebettens, M}, title = {The TORNADO1 and TORNADO2 genes function in several patterning processes during early leaf development in Arabidopsis thaliana.}, journal = {The Plant cell}, volume = {18}, number = {4}, pages = {852-866}, pmid = {16531491}, issn = {1040-4651}, mesh = {Arabidopsis/classification/*genetics/*growth & development ; Arabidopsis Proteins/*genetics ; Conserved Sequence ; Cotyledon/anatomy & histology/physiology ; DNA Primers ; *Gene Expression Regulation, Developmental ; *Genes, Plant ; Homeostasis ; Indoleacetic Acids/metabolism ; Molecular Sequence Data ; Mutation ; Phylogeny ; Plant Leaves/anatomy & histology/*growth & development ; Polymerase Chain Reaction ; }, abstract = {In multicellular organisms, patterning is a process that generates axes in the primary body plan, creates domains upon organ formation, and finally leads to differentiation into tissues and cell types. We identified the Arabidopsis thaliana TORNADO1 (TRN1) and TRN2 genes and their role in leaf patterning processes such as lamina venation, symmetry, and lateral growth. In trn mutants, the leaf venation network had a severely reduced complexity: incomplete loops, no tertiary or quaternary veins, and vascular islands. The leaf laminas were asymmetric and narrow because of a severely reduced cell number. We postulate that the imbalance between cell proliferation and cell differentiation and the altered auxin distribution in both trn mutants cause asymmetric leaf growth and aberrant venation patterning. TRN1 and TRN2 were epistatic to ASYMMETRIC LEAVES1 with respect to leaf asymmetry, consistent with their expression in the shoot apical meristem and leaf primordia. TRN1 codes for a large plant-specific protein with conserved domains also found in a variety of signaling proteins, whereas TRN2 encodes a transmembrane protein of the tetraspanin family whose phylogenetic tree is presented. Double mutant analysis showed that TRN1 and TRN2 act in the same pathway.}, } @article {pmid16529956, year = {2006}, author = {Tsui, CK and Berbee, ML}, title = {Phylogenetic relationships and convergence of helicosporous fungi inferred from ribosomal DNA sequences.}, journal = {Molecular phylogenetics and evolution}, volume = {39}, number = {3}, pages = {587-597}, doi = {10.1016/j.ympev.2006.01.025}, pmid = {16529956}, issn = {1055-7903}, mesh = {DNA, Ribosomal/*genetics ; Fungi/classification/*genetics ; *Phylogeny ; Polymerase Chain Reaction ; }, abstract = {Helicosporous fungi form elegant, coiled, and multicellular mitotic spores (conidia). In this paper, we investigate the phylogenetic relationships among helicosporous fungi in the asexual genera Helicoma, Helicomyces, Helicosporium, Helicodendron, Helicoon, and in the sexual genus Tubeufia (Tubeufiaceae, Dothideomycetes, and Ascomycota). We generated ribosomal small subunit and partial large subunit sequences from 39 fungal cultures. These and related sequences from GenBank were analyzed using parsimony, likelihood, and Bayesian analysis. Results showed that helicosporous species arose convergently from six lineages of fungi in the Ascomycota. The Tubeufiaceae s. str. formed a strongly supported monophyletic lineage comprising most species from Helicoma, Helicomyces, and Helicosporium. However, within the Tubeufiaceae, none of the asexual genera were monophyletic. Traditional generic characters, such as whether conidiophores were conspicuous or reduced, the thickness of the conidial filament, and whether or not conidia were hygroscopic, were more useful for species delimitation than for predicting higher level relationships. In spite of their distinctive, barrel-shaped spores, Helicoon species were polyphyletic and had evolved in different ascomycete orders. Helicodendron appeared to be polyphyletic although most representatives occurred within Leotiomycetes. We speculate that some of the convergent spore forms may represent adaptation to dispersal in aquatic environments.}, } @article {pmid16522221, year = {2006}, author = {Kruse, E and Uehlein, N and Kaldenhoff, R}, title = {The aquaporins.}, journal = {Genome biology}, volume = {7}, number = {2}, pages = {206}, pmid = {16522221}, issn = {1474-760X}, mesh = {Animals ; Aquaporins/chemistry/*genetics ; Bacteria/genetics ; Evolution, Molecular ; Humans ; Models, Molecular ; Plant Proteins/genetics ; Protein Conformation ; Vertebrates ; }, abstract = {Water is the major component of all living cells, and efficient regulation of water homeostasis is essential for many biological processes. The mechanism by which water passes through biological membranes was a matter of debate until the discovery of the aquaporin water channels. Aquaporins are intrinsic membrane proteins characterized by six transmembrane helices that selectively allow water or other small uncharged molecules to pass along the osmotic gradient. In addition, recent observations show that some aquaporins also facilitate the transport of volatile substances, such as carbon dioxide (CO2) and ammonia (NH3), across membranes. Aquaporins usually form tetramers, with each monomer defining a single pore. Aquaporin-related proteins are found in all organisms, from archaea to mammals. In both uni- and multicellular organisms, numerous isoforms have been identified that are differentially expressed and modified by post-translational processes, thus allowing fine-tuned tissue-specific osmoregulation. In mammals, aquaporins are involved in multiple physiological processes, including kidney and salivary gland function. They are associated with several clinical disorders, such as kidney dysfunction, loss of vision and brain edema.}, } @article {pmid16514144, year = {2006}, author = {Kurenbach, B and Kopeć, J and Mägdefrau, M and Andreas, K and Keller, W and Bohn, C and Abajy, MY and Grohmann, E}, title = {The TraA relaxase autoregulates the putative type IV secretion-like system encoded by the broad-host-range Streptococcus agalactiae plasmid pIP501.}, journal = {Microbiology (Reading, England)}, volume = {152}, number = {Pt 3}, pages = {637-645}, doi = {10.1099/mic.0.28468-0}, pmid = {16514144}, issn = {1350-0872}, mesh = {Bacterial Proteins/genetics/*metabolism ; Base Sequence ; Conjugation, Genetic ; DNA Nucleotidyltransferases/chemistry/genetics/*metabolism ; Enterococcus faecalis/genetics/*metabolism ; *Gene Expression Regulation, Bacterial ; Gene Transfer, Horizontal ; Molecular Sequence Data ; Operon ; Plasmids/*genetics ; Promoter Regions, Genetic ; Streptococcus agalactiae/*genetics ; Transcription, Genetic ; }, abstract = {The conjugative multiple antibiotic resistance plasmid pIP501 can be transferred and stably maintained in a variety of Gram-positive genera, including multicellular Streptomyces lividans, as well as in Gram-negative Escherichia coli. The 15 putative pIP501 transfer (tra) genes are organized in an operon-like structure terminating in a strong transcriptional terminator. This paper reports co-transcription of the pIP501 tra genes in exponentially growing Enterococcus faecalis JH2-2 cells, as shown by RT-PCR. The tra genes are expressed throughout the life cycle of Ent. faecalis, and the expression level is independent of the growth phase. Electrophoretic mobility shift assays indicated that the TraA relaxase, the first gene of the tra operon, binds to the tra promoter P(tra), which partially overlaps with the origin of transfer (oriT). DNase I footprinting experiments further delimited the TraA binding region and defined the nucleotides bound by TraA. Beta-Galactosidase assays with P(tra)-lacZ fusions proved P(tra) promoter activity, which was strongly repressed when TraA was supplied in trans. Thus, it is concluded that the pIP501 tra operon is negatively autoregulated at the transcriptional level by the conjugative DNA relaxase TraA.}, } @article {pmid16509995, year = {2006}, author = {Khaitan, D and Chandna, S and Arya, MB and Dwarakanath, BS}, title = {Establishment and characterization of multicellular spheroids from a human glioma cell line; Implications for tumor therapy.}, journal = {Journal of translational medicine}, volume = {4}, number = {}, pages = {12}, pmid = {16509995}, issn = {1479-5876}, abstract = {BACKGROUND: Multicellular spheroids, an appropriate in vitro system for simulating 3-D tumor micro-milieu can be used for evaluating and predicting tumor response to therapeutic agents including metabolic inhibitors. However, detailed understanding of the nature, distribution and sensitivity/responses of cellular sub-populations to potential therapeutic agents/strategies is required for using this unique model with optimal precision. Spheroid characteristics may also vary considerably with the origin and type of cell line used, and thorough characterization of viable and dissociated glioma cell spheroids is not yet completely known. In order to evaluate in vivo responses of gliomas to various therapeutic strategies, especially the metabolic inhibitors capable of penetrating the blood brain barrier, we have characterized continuously growing spheroids of a human glioma cell line (BMG-1) with respect to organization, growth, viability, cell survival, cell death, metabolic and mitochondrial status, oxidative stress and radiation response using microscopy, flow cytometry and enzymatic assays. Spheroids were fed daily with fresh medium in order to maintain nutrient supply to outer cellular layers while hypoxia/necrosis developed in the innermost cells of enlarging spheroids.

RESULTS: Volume of spheroids, fed daily with fresh medium, increased exponentially during 7-28 days of growth through three population doublings. Proportion of G1-phase cells was higher (approximately 60%) than exponentially growing monolayer cells (approximately 48%). A significant fraction of S-phase cells turned metabolically inactive (disengaged in DNA synthesis) with increasing age of the spheroids, unlike in quiescent monolayer cultures, where the fraction of S-phase cells was less than 5%. With increasing spheroid size, increasing sub-populations of cells became non-viable and entered apoptosis or necrosis revealed by Annexin-V-FITC/PI staining. PI positive (necrotic) cells were not confined to the centre of the spheroid, but distributed at certain discrete foci. Average glucose consumption and lactate production were 2-3 folds higher in viable spheroid cells compared to monolayer cells, implying a compensatory increase in glycolysis possibly due to hypoxic environment. HIF-1alpha was expressed only in spheroids and increased in an age-dependent manner, whereas c-Myc (known to induce apoptosis in glucose-deprived cells) levels were three times higher than monolayer cells. Mitochondrial mass and activity decreased significantly during first 14 days of growth but increased with age, and were not associated with increase in ROS levels. Bcl-2 and Bax levels were higher (approximately 2 folds) than monolayers, while the ratio (Bcl/Bax) remained unaltered. Radiation-induced oxidative stress was considerably less in spheroids as compared to monolayers, and corresponded well with increase in radioresistance demonstrated by the clonogenic assay, similar to hypoxia induced radioresistance observed in tumors.

CONCLUSION: Development of S-negative cells and reduced endogenous and radiation-induced ROS coupled with higher levels of anti (Bcl2) as well as pro (Bax) apoptotic regulators observed in spheroids suggest the intricate/complex nature of endogenous as well as induced stress resistance that could exist in tumors, which contribute to the treatment resistance.}, } @article {pmid16509894, year = {2006}, author = {Larroux, C and Fahey, B and Liubicich, D and Hinman, VF and Gauthier, M and Gongora, M and Green, K and Wörheide, G and Leys, SP and Degnan, BM}, title = {Developmental expression of transcription factor genes in a demosponge: insights into the origin of metazoan multicellularity.}, journal = {Evolution & development}, volume = {8}, number = {2}, pages = {150-173}, doi = {10.1111/j.1525-142X.2006.00086.x}, pmid = {16509894}, issn = {1520-541X}, mesh = {Amino Acid Sequence ; Animals ; Binding Sites ; *Biological Evolution ; DNA/metabolism ; Gene Expression Regulation, Developmental/*physiology ; Larva/cytology/genetics/metabolism ; Ligands ; Molecular Sequence Data ; Porifera/*cytology/*embryology/genetics/metabolism ; Protein Structure, Tertiary ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/biosynthesis/*genetics ; }, abstract = {Demosponges are considered part of the most basal evolutionary lineage in the animal kingdom. Although the sponge body plan fundamentally differs from that of other metazoans, their development includes many of the hallmarks of bilaterian and eumetazoan embryogenesis, namely fertilization followed by a period of cell division yielding distinct cell populations, which through a gastrulation-like process become allocated into different cell layers and patterned within these layers. These observations suggest that the last common ancestor (LCA) to all living animals was developmentally more sophisticated than is widely appreciated and used asymmetric cell division and morphogen gradients to establish localized populations of specified cells within the embryo. Here we demonstrate that members of a range of transcription factor gene classes, many of which appear to be metazoan-specific, are expressed during the development of the demosponge Reniera, including ANTP, Pax, POU, LIM-HD, Sox, nuclear receptor, Fox (forkhead), T-box, Mef2, and Ets genes. Phylogenetic analysis of these genes suggests that not only the origin but the diversification of some of the major developmental metazoan transcription factor classes took place before sponges diverged from the rest of the Metazoa. Their expression during demosponge development suggests that, as in today's sophisticated metazoans, these genes may have functioned in the regulatory network of the metazoan LCA to control cell specification and regionalized gene expression during embryogenesis.}, } @article {pmid16501584, year = {2006}, author = {Keller, L and Surette, MG}, title = {Communication in bacteria: an ecological and evolutionary perspective.}, journal = {Nature reviews. Microbiology}, volume = {4}, number = {4}, pages = {249-258}, doi = {10.1038/nrmicro1383}, pmid = {16501584}, issn = {1740-1526}, mesh = {Bacteria/*metabolism ; *Bacterial Physiological Phenomena ; Bacterial Proteins/genetics/physiology ; *Biological Evolution ; Gene Expression Regulation, Bacterial ; Signal Transduction ; }, abstract = {Individual bacteria can alter their behaviour through chemical interactions between organisms in microbial communities - this is generally referred to as quorum sensing. Frequently, these interactions are interpreted in terms of communication to mediate coordinated, multicellular behaviour. We show that the nature of interactions through quorum-sensing chemicals does not simply involve cooperative signals, but entails other interactions such as cues and chemical manipulations. These signals might have a role in conflicts within and between species. The nature of the chemical interaction is important to take into account when studying why and how bacteria react to the chemical substances that are produced by other bacteria.}, } @article {pmid16495312, year = {2006}, author = {MacWilliams, H and Doquang, K and Pedrola, R and Dollman, G and Grassi, D and Peis, T and Tsang, A and Ceccarelli, A}, title = {A retinoblastoma ortholog controls stalk/spore preference in Dictyostelium.}, journal = {Development (Cambridge, England)}, volume = {133}, number = {7}, pages = {1287-1297}, doi = {10.1242/dev.02287}, pmid = {16495312}, issn = {0950-1991}, mesh = {Amino Acid Sequence ; Animals ; Cell Cycle ; Cell Differentiation ; Cell Nucleus/chemistry ; Cell Size ; Conserved Sequence ; DNA, Protozoan/analysis ; Dictyostelium/*cytology/genetics/*growth & development ; Dose-Response Relationship, Drug ; Evolution, Molecular ; Fluorescent Dyes ; Gene Expression Regulation/drug effects ; *Genes, Protozoan ; *Genes, Retinoblastoma ; Glucose/pharmacology ; Hexanones/pharmacology ; Indoles ; Molecular Sequence Data ; Mutation ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Protozoan Proteins/genetics/*physiology ; Sequence Homology, Amino Acid ; *Spores, Protozoan ; }, abstract = {We describe rblA, the Dictyostelium ortholog of the retinoblastoma susceptibility gene Rb. In the growth phase, rblA expression is correlated with several factors that lead to 'preference' for the spore pathway. During multicellular development, expression increases 200-fold in differentiating spores. rblA-null strains differentiate stalk cells and spores normally, but in chimeras with wild type, the mutant shows a strong preference for the stalk pathway. rblA-null cells are hypersensitive to the stalk morphogen DIF, suggesting that rblA normally suppresses the DIF response in cells destined for the spore pathway. rblA overexpression during growth leads to G1 arrest, but as growing Dictyostelium are overwhelmingly in G2 phase, rblA does not seem to be important in the normal cell cycle. rblA-null cells show reduced cell size and a premature growth-development transition; the latter appears anomalous but may reflect selection pressures acting on social ameba.}, } @article {pmid16495042, year = {2006}, author = {Maiorano, D and Lutzmann, M and Méchali, M}, title = {MCM proteins and DNA replication.}, journal = {Current opinion in cell biology}, volume = {18}, number = {2}, pages = {130-136}, doi = {10.1016/j.ceb.2006.02.006}, pmid = {16495042}, issn = {0955-0674}, mesh = {Animals ; Cell Cycle Proteins/genetics/*physiology ; *DNA Replication ; DNA-Binding Proteins/genetics/physiology ; Humans ; Models, Genetic ; Nuclear Proteins/genetics/*physiology ; Phylogeny ; Transcription Factors/genetics/physiology ; }, abstract = {The MCM proteins identify a group of ten conserved factors functioning in the replication of the genomes of archae and eukaryotic organisms. Among these, MCM2-7 proteins are related to each other and form a family of DNA helicases implicated at the initiation step of DNA synthesis. Recently this family expanded by the identification of two additional members that appear to be present only in multicellular organisms, MCM8 and MCM9. The function of MCM8 is distinct from that of MCM2-7 proteins, while the function of MCM9 is unknown. MCM1 and MCM10 are not related to this family, nor to each other, but also function in DNA synthesis.}, } @article {pmid16479496, year = {2006}, author = {Newman, SA and Forgacs, G and Muller, GB}, title = {Before programs: the physical origination of multicellular forms.}, journal = {The International journal of developmental biology}, volume = {50}, number = {2-3}, pages = {289-299}, doi = {10.1387/ijdb.052049sn}, pmid = {16479496}, issn = {0214-6282}, mesh = {Animals ; *Biological Evolution ; Cell Physiological Phenomena ; Cells/*cytology ; Epigenesis, Genetic/physiology ; }, abstract = {By examining the formative role of physical processes in modern-day developmental systems, we infer that although such determinants are subject to constraints and rarely act in a "pure" fashion, they are identical to processes generic to all viscoelastic, chemically excitable media, non-living as well as living. The processes considered are free diffusion, immiscible liquid behavior, oscillation and multistability of chemical state, reaction-diffusion coupling and mechanochemical responsivity. We suggest that such processes had freer reign at early stages in the history of multicellular life, when less evolution had occurred of genetic mechanisms for stabilization and entrenchment of functionally successful morphologies. From this we devise a hypothetical scenario for pattern formation and morphogenesis in the earliest metazoa. We show that the expected morphologies that would arise during this relatively unconstrained "physical" stage of evolution correspond to the hollow, multilayered and segmented morphotypes seen in the gastrulation stage embryos of modern-day metazoa as well as in Ediacaran fossil deposits of approximately 600 Ma. We suggest several ways in which organisms that were originally formed by predominantly physical mechanisms could have evolved genetic mechanisms to perpetuate their morphologies.}, } @article {pmid16479486, year = {2006}, author = {Cherdantsev, VG}, title = {The dynamic geometry of mass cell movements in animal morphogenesis.}, journal = {The International journal of developmental biology}, volume = {50}, number = {2-3}, pages = {169-182}, doi = {10.1387/ijdb.052060vc}, pmid = {16479486}, issn = {0214-6282}, mesh = {Animals ; Cell Movement/*physiology ; Embryo, Nonmammalian ; Morphogenesis/*physiology ; }, abstract = {There is an infinite number of interactions between morphogenetic processes of different time and space scales. How do these unfold in a regular series of mass morphogenetic movements to produce a basically simple and reproducible structure? I present a new morphogenetic concept -- the spatial unfolding (SU) of cell movements, whose definition rests on the correspondence between the continuous spatial series of cell shapes and the succession of changes in the shape of a single cell moving in an epithelial sheet whose shape is also subject to change. The change in the shape of moving cells is the only measure of their translocation both in space and time. The SU provides a morpho-dynamics description of mass cell movements which is completely independent of both an external coordinate system and external forces. The cell geometry of SU allows us to derive the future embryonic form from the actual one by a movement-shaping algorithm operating on the basis of positive and negative geometric feedbacks between the cell movement in the epithelial sheet plane and the epithelial sheet shaping, the feedback system providing a geometric alternative to Turing's self-organization via reaction-diffusion systems. Putting together histological, quantitative morphological and experimental data permits us to isolate four SU, each acting in morphogenesis as an irreducible whole, which seem to include all real examples of epithelial morphogenesis in multicellular animals, from Coelenterates to Chordates.}, } @article {pmid16471257, year = {2005}, author = {Ameisen, JC}, title = {[Selective "death programs" or pleiotropic"life programs"? Looking for programmed cell death in the light of evolution].}, journal = {Journal de la Societe de biologie}, volume = {199}, number = {3}, pages = {175-189}, doi = {10.1051/jbio:2005018}, pmid = {16471257}, issn = {1295-0661}, mesh = {Aging/physiology ; Animals ; Apoptosis/genetics/*physiology ; Apoptosis Regulatory Proteins/classification/genetics/*physiology ; Bacteria/cytology ; *Biological Evolution ; Caenorhabditis elegans/cytology/embryology/genetics ; Eukaryotic Cells/cytology ; Evolution, Molecular ; Humans ; Infections/pathology ; *Life ; Models, Biological ; Phylogeny ; Symbiosis/physiology ; Vitalism ; }, abstract = {"Nothing in biology makes sense except in the light of evolution", wrote Theodosius Dobzhansky, one of the founders of the Modern Synthesis that led to the unification of evolutionary theory and genetics in the midst of the 20th century. Programmed cell death is a genetically regulated process of cell suicide that is central to the development, homeostasis and integrity of multicellular organisms. Conversely, the dysregulation of mechanisms controlling cell suicide plays a role in the pathogenesis of a wide range of diseases. While great progress has been achieved in the unveiling of the molecular mechanisms of programmed cell death, a new, and somehow puzzling level of complexity has recently begun to emerge, suggesting i) that several different self destruction pathways may exist and operate in parallel in our cells, and ii) that molecular effectors of cell suicide might also perform other functions unrelated to cell death induction and crucial to cell survival, such as cell differentiation, metabolism, and the regulation of the cell cycle. These new findings, with important physiopathological and therapeutic implications, seem at odds with the paradigm of programmed cell death derived from the studies of Caenorhabditis elegans, which led to the concept of the existence of selective, bona fide death genes that emerged and became selected for their sole capacity to execute or repress cell death. In this review, I will argue that this new level of complexity might only make sense and be understood when considered in a broader evolutionary context than that of our phylogenetic divergence from C. elegans. A new view of the regulated cell death pathways emerges when one attempts to ask the question of when and how they may have become selected during a timeline of 4 billion years, at the level of ancestral single-celled organisms, including the bacteria. I will argue that there may be no such thing as a bona fide genetic cell death program. Rather, in the framework of a model that I have termed the "original sin" hypothesis, I have proposed the existence of an initial pleiotropy of the molecular tools involved in the control and execution of self-destruction--an ancestral involvement in both pro-life and pro-death activities. I will discuss how this hypothesis may be reconciled with the C. elegans paradigm of programmed cell death. Finally I will discuss how an ancestral level of pleiotropic functions of the molecular tools involved in the control of cell death, aging and genetic diversification might have favored their initial selection, their constant availability for de novo selection, and their progressive propagation in most--if not all--species during the course of evolution.}, } @article {pmid16469852, year = {2006}, author = {Haygood, R and , }, title = {Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. Mutation rate and the cost of complexity.}, journal = {Molecular biology and evolution}, volume = {23}, number = {5}, pages = {957-963}, doi = {10.1093/molbev/msj104}, pmid = {16469852}, issn = {0737-4038}, mesh = {Animals ; Biological Evolution ; Genetic Variation ; Genetics, Population ; Genome ; Genomics/methods ; *Models, Genetic ; Models, Statistical ; *Mutation ; Phenotype ; Phylogeny ; Selection, Genetic ; }, abstract = {Two recent theoretical studies of adaptation suggest that more complex organisms tend to adapt more slowly. Specifically, in Fisher's "geometric" model of a finite population where multiple traits are under optimizing selection, the average progress ensuing from a single mutation decreases as the number of traits increases--the "cost of complexity." Here, I draw on molecular and histological data to assess the extent to which on a large phylogenetic scale, this predicted decrease in the rate of adaptation per mutation is mitigated by an increase in the number of mutations per generation as complexity increases. As an index of complexity for multicellular organisms, I use the number of visibly distinct types of cell in the body. Mutation rate is the product of mutational target size and population mutation rate per unit target. Despite much scatter, genome size appears to be positively correlated with complexity (as indexed by cell-type number), which along with other considerations suggests that mutational target size tends to increase with complexity. In contrast, effective population mutation rate per unit target appears to be negatively correlated with complexity. The net result is that mutation rate probably does tend to increase with complexity, although probably not fast enough to eliminate the cost of complexity.}, } @article {pmid16469305, year = {2006}, author = {Chubb, JR and Bloomfield, G and Xu, Q and Kaller, M and Ivens, A and Skelton, J and Turner, BM and Nellen, W and Shaulsky, G and Kay, RR and Bickmore, WA and Singer, RH}, title = {Developmental timing in Dictyostelium is regulated by the Set1 histone methyltransferase.}, journal = {Developmental biology}, volume = {292}, number = {2}, pages = {519-532}, doi = {10.1016/j.ydbio.2005.12.054}, pmid = {16469305}, issn = {0012-1606}, support = {G120/1013(75407)/MRC_/Medical Research Council/United Kingdom ; MC_U105115237/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; Biomarkers/metabolism ; Blotting, Western ; Cell Differentiation ; Chromatin Immunoprecipitation ; Cluster Analysis ; Dictyostelium/*growth & development ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Genes, Protozoan ; Genome, Protozoan ; Genomics ; Histone Methyltransferases ; Histone-Lysine N-Methyltransferase/chemistry/genetics/*metabolism ; Histones/chemistry/*metabolism ; Luminescent Measurements ; Lysine/metabolism ; Methylation ; Molecular Sequence Data ; Mutation ; Oligonucleotide Array Sequence Analysis ; Phylogeny ; Protein Methyltransferases ; Protein Structure, Tertiary ; Protozoan Proteins/chemistry/genetics/*metabolism ; Sequence Homology, Amino Acid ; Time Factors ; Transcription, Genetic ; }, abstract = {Histone-modifying enzymes have enormous potential as regulators of the large-scale changes in gene expression occurring during differentiation. It is unclear how different combinations of histone modification coordinate regimes of transcription during development. We show that different methylation states of lysine 4 of histone H3 (H3K4) mark distinct developmental phases of the simple eukaryote, Dictyostelium. We demonstrate that the enzyme responsible for all mono, di and tri-methylation of H3K4 is the Dictyostelium homolog of the Set1 histone methyltransferase. In the absence of Set1, cells display unusually rapid development, characterized by precocious aggregation of amoebae into multicellular aggregates. Early differentiation markers are abundantly expressed in growing set1 cells, indicating the differentiation program is ectopically activated during growth. This phenotype is caused specifically by the loss of Set1 catalytic activity. Set1 mutants induce premature differentiation in wild-type cells, indicating Set1 regulates production of an extra-cellular factor required for the correct perception of growth conditions. Microarray analysis of the set1 mutants reveals genomic clustering of mis-expressed genes, suggesting a requirement for Set1 in the regulation of chromatin-mediated events at gene clusters.}, } @article {pmid16453157, year = {2006}, author = {Lakämper, S and Meyhöfer, E}, title = {Back on track - on the role of the microtubule for kinesin motility and cellular function.}, journal = {Journal of muscle research and cell motility}, volume = {27}, number = {2}, pages = {161-171}, pmid = {16453157}, issn = {0142-4319}, mesh = {Animals ; Biological Transport/physiology ; Cell Movement/*physiology ; Cilia/genetics/metabolism ; Cytoskeleton/genetics/*metabolism ; Flagella/genetics/metabolism ; Humans ; Kinesins/genetics/*metabolism ; Microtubules/genetics/*metabolism ; Protein Processing, Post-Translational/physiology ; }, abstract = {The evolution of cytoskeletal filaments (actin- and intermediate-filaments, and the microtubules) and their associated motor- and non-motor-proteins has enabled the eukaryotic cell to achieve complex organizational and structural tasks. This ability to control cellular transport processes and structures allowed for the development of such complex cellular organelles like cilia or flagella in single-cell organisms and made possible the development and differentiation of multi-cellular organisms with highly specialized, polarized cells. Also, the faithful segregation of large amounts of genetic information during cell division relies crucially on the reorganization and control of the cytoskeleton, making the cytoskeleton a key prerequisite for the development of highly complex genomes. Therefore, it is not surprising that the eukaryotic cell continuously invests considerable resources in the establishment, maintenance, modification and rearrangement of the cytoskeletal filaments and the regulation of its interaction with accessory proteins. Here we review the literature on the interaction between microtubules and motor-proteins of the kinesin-family. Our particular interest is the role of the microtubule in the regulation of kinesin motility and cellular function. After an introduction of the kinesin-microtubule interaction we focus on two interrelated aspects: (1) the active allosteric participation of the microtubule during the interaction with kinesins in general and (2) the possible regulatory role of post-translational modifications of the microtubule in the kinesin-microtubule interaction.}, } @article {pmid16452927, year = {2006}, author = {Elena, SF and Carrasco, P and Daròs, JA and Sanjuán, R}, title = {Mechanisms of genetic robustness in RNA viruses.}, journal = {EMBO reports}, volume = {7}, number = {2}, pages = {168-173}, pmid = {16452927}, issn = {1469-221X}, mesh = {*Evolution, Molecular ; Genetics, Population ; Genome, Viral ; Models, Genetic ; Mutation ; RNA Viruses/*genetics ; RNA, Viral ; Selection, Genetic ; Virus Replication ; }, abstract = {Two key features of RNA viruses are their compacted genomes and their high mutation rate. Accordingly, deleterious mutations are common and have an enormous impact on viral fitness. In their multicellular hosts, robustness can be achieved by genomic redundancy, including gene duplication, diploidy, alternative metabolic pathways and biochemical buffering mechanisms. However, here we review evidence suggesting that during RNA virus evolution, alternative robustness mechanisms may have been selected. After briefly describing how genetic robustness can be quantified, we discuss mechanisms of intrinsic robustness arising as consequences of RNA-genome architecture, replication peculiarities and quasi-species population dynamics. These intrinsic robustness mechanisms operate efficiently at the population level, despite the mutational sensitivity shown by individual genomes. Finally, we discuss the possibility that viruses might exploit cellular buffering mechanisms for their own benefit, producing a sort of extrinsic robustness.}, } @article {pmid16434393, year = {2006}, author = {Short, KM and Cox, TC}, title = {Subclassification of the RBCC/TRIM superfamily reveals a novel motif necessary for microtubule binding.}, journal = {The Journal of biological chemistry}, volume = {281}, number = {13}, pages = {8970-8980}, doi = {10.1074/jbc.M512755200}, pmid = {16434393}, issn = {0021-9258}, mesh = {Adaptor Proteins, Signal Transducing/*classification/*metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Blotting, Western ; COS Cells ; Chlorocebus aethiops ; Computational Biology ; Consensus Sequence ; Databases, Factual ; Fluorescent Antibody Technique ; Fluorescent Dyes ; Green Fluorescent Proteins/metabolism ; Humans ; Markov Chains ; Membrane Proteins/*classification/*metabolism ; Microscopy, Confocal ; Microtubules/*metabolism ; Molecular Sequence Data ; Mutation ; Phylogeny ; Precipitin Tests ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Transcription Factors/*chemistry/genetics/isolation & purification/*metabolism ; Transfection ; Two-Hybrid System Techniques ; Xanthenes ; Zinc Fingers ; }, abstract = {The biological significance of RBCC (N-terminal RING finger/B-box/coiled coil) proteins is increasingly being appreciated following demonstrated roles in disease pathogenesis, tumorigenesis, and retroviral protective activity. Found in all multicellular eukaryotes, RBCC proteins are involved in a vast array of intracellular functions; but as a general rule, they appear to function as part of large protein complexes and possess ubiquitin-protein isopeptide ligase activity. Those members characterized to date have diverse C-terminal domain compositions and equally diverse subcellular localizations and functions. Using a bioinformatics approach, we have identified some new RBCC proteins that help define a subfamily that shares an identical domain arrangement (MID1, MID2, TRIM9, TNL, TRIM36, and TRIFIC). Significantly, we show that all analyzed members of this subfamily associate with the microtubule cytoskeleton, suggesting that subcellular compartmentalization is determined by the unique domain architecture, which may in turn reflect basic functional similarities. We also report a new motif called the COS box, which is found within these proteins, the MURF family, and a distantly related non-RBCC microtubule-binding protein. Notably, we demonstrate that mutations in the COS box abolish microtubule binding ability, whereas its incorporation into a nonmicrotubule-binding RBCC protein redirects it to microtubule structures. Further bioinformatics investigation permitted subclassification of the entire human RBCC complement into nine subfamilies based on their varied C-terminal domain compositions. This classification schema may aid the understanding of the molecular function of members of each subgroup and their potential involvement in both basic cellular processes and human disease.}, } @article {pmid16431025, year = {2006}, author = {Lauc, G}, title = {Sweet secret of the multicellular life.}, journal = {Biochimica et biophysica acta}, volume = {1760}, number = {4}, pages = {525-526}, doi = {10.1016/j.bbagen.2005.12.010}, pmid = {16431025}, issn = {0006-3002}, mesh = {Evolution, Molecular ; *Glycoproteins/chemistry/genetics/physiology ; Glycosylation ; Humans ; Polysaccharides ; Proteomics ; }, } @article {pmid16391664, year = {2005}, author = {Xu, J}, title = {The inheritance of organelle genes and genomes: patterns and mechanisms.}, journal = {Genome}, volume = {48}, number = {6}, pages = {951-958}, doi = {10.1139/g05-082}, pmid = {16391664}, issn = {0831-2796}, mesh = {Animals ; *Evolution, Molecular ; *Genome ; Humans ; *Inheritance Patterns ; Organelles/*genetics ; }, abstract = {Unlike nuclear genes and genomes, the inheritance of organelle genes and genomes does not follow Mendel's laws. In this mini-review, I summarize recent research progress on the patterns and mechanisms of the inheritance of organelle genes and genomes. While most sexual eukaryotes show uniparental inheritance of organelle genes and genomes in some progeny at least part of the time, increasing evidence indicates that strictly uniparental inheritance is rare and that organelle inheritance patterns are very diverse and complex. In contrast with the predominance of uniparental inheritance in multicellular organisms, organelle genes in eukaryotic microorganisms, such as protists, algae, and fungi, typically show a greater diversity of inheritance patterns, with sex-determining loci playing significant roles. The diverse patterns of inheritance are matched by the rich variety of potential mechanisms. Indeed, many factors, both deterministic and stochastic, can influence observed patterns of organelle inheritance. Interestingly, in multicellular organisms, progeny from interspecific crosses seem to exhibit more frequent paternal leakage and biparental organelle genome inheritance than those from intraspecific crosses. The recent observation of a sex-determining gene in the basidiomycete yeast Cryptococcus neoformans, which controls mitochondrial DNA inheritance, has opened up potentially exciting research opportunities for identifying specific molecular genetic pathways that control organelle inheritance, as well as for testing evolutionary hypotheses regarding the prevalence of uniparental inheritance of organelle genes and genomes.}, } @article {pmid16385324, year = {2006}, author = {Gottfried, ON and Viskochil, DH and Fults, DW and Couldwell, WT}, title = {Molecular, genetic, and cellular pathogenesis of neurofibromas and surgical implications.}, journal = {Neurosurgery}, volume = {58}, number = {1}, pages = {1-16; discussion 1-16}, doi = {10.1227/01.neu.0000190651.45384.8b}, pmid = {16385324}, issn = {1524-4040}, mesh = {Animals ; Disease Models, Animal ; Genes, Neurofibromatosis 1 ; Growth Substances/metabolism ; Humans ; Loss of Heterozygosity ; Mutation ; Nerve Sheath Neoplasms/genetics ; Neurofibroma/*genetics/*metabolism/pathology/surgery ; Neurofibromatosis 1/genetics/metabolism/pathology ; Neurofibromin 1/metabolism ; Receptors, Cell Surface/metabolism ; Schwann Cells/pathology ; }, abstract = {Neurofibromatosis 1 (NF1) is a common autosomal dominant disease characterized by complex and multicellular neurofibroma tumors. Significant advances have been made in the research of the cellular, genetic, and molecular biology of NF1. The NF1 gene was identified by positional cloning. The functions of its protein product, neurofibromin, in RAS signaling and in other signal transduction pathways are being elucidated, and the important roles of loss of heterozygosity and haploinsufficiency in tumorigenesis are better understood. The Schwann cell was discovered to be the cell of origin for neurofibromas, but understanding of a more complicated interplay of multiple cell types in tumorigenesis, specifically recruited heterogeneous cell types such as mast cells and fibroblasts, has important implications for surgical therapy of these tumors. This review summarizes the most recent NF1 and neurofibroma literature describing the pathogenesis and treatment of nerve sheath tumors. Understanding the biological underpinnings of tumorigenesis in NF1 has implications for future surgical and medical management of neurofibromas.}, } @article {pmid16382166, year = {2005}, author = {Mashanov, VS and Dolmatov, IY and Heinzeller, T}, title = {Transdifferentiation in holothurian gut regeneration.}, journal = {The Biological bulletin}, volume = {209}, number = {3}, pages = {184-193}, doi = {10.2307/3593108}, pmid = {16382166}, issn = {0006-3185}, mesh = {Animals ; Cell Differentiation/*physiology ; Epithelial Cells/cytology/ultrastructure ; Gastrointestinal Tract/physiology/ultrastructure ; Holothuria/*physiology/ultrastructure ; Microscopy, Electron, Transmission ; Regeneration/*physiology ; }, abstract = {It has recently been shown that the whole spectrum of cell types constituting a multicellular organism can be generated from stem cells. Our study provides an example of an alternative mechanism of tissue repair. Injection of distilled water into the coelomic cavity of the holothurian Eupentacta fraudatrix results in the loss of the whole digestive tract, except the cloaca. The new gut reforms from two separate rudiments. One rudiment appears at the anterior end of the body and extends posteriorly. The second rudiment grows anteriorly from the cloaca. In the anterior rudiment, the luminal epithelium (normally derived from endoderm) develops de novo through direct transdifferentiation of the coelomic epithelial cells (mesodermal in origin). In the posterior rudiment, the luminal epithelium originates from the lining epithelium of the cloaca. After 27 days, the two rudiments come into contact and fuse to form a continuous digestive tube lined with a fully differentiated luminal epithelium. Thus in this species, the luminal epithelia of the anterior and posterior gut rudiments develop from two different cell sources-i.e., from the mesodermally derived mesothelium and the endodermally derived epithelium of the cloacal lining, respectively. Our data suggest that differentiated cells of echinoderms are capable of transdifferentiation into other cell types.}, } @article {pmid16373568, year = {2005}, author = {Pittermann, J and Sperry, JS and Hacke, UG and Wheeler, JK and Sikkema, EH}, title = {Torus-margo pits help conifers compete with angiosperms.}, journal = {Science (New York, N.Y.)}, volume = {310}, number = {5756}, pages = {1924}, doi = {10.1126/science.1120479}, pmid = {16373568}, issn = {1095-9203}, mesh = {Adaptation, Physiological ; Biological Evolution ; Biological Transport ; Magnoliopsida/physiology ; Membranes/physiology ; Plant Structures/physiology ; Tracheophyta/anatomy & histology/*physiology ; Trees/physiology ; Water ; }, abstract = {The unicellular conifer tracheid should have greater flow resistance per length (resistivity) than the multicellular angiosperm vessel, because its high-resistance end-walls are closer together. However, tracheids and vessels had comparable resistivities for the same diameter, despite tracheids being over 10 times shorter. End-wall pits of tracheids averaged 59 times lower flow resistance on an area basis than vessel pits, owing to the unique torus-margo structure of the conifer pit membrane. The evolution of this membrane was as hydraulically important as that of vessels. Without their specialized pits, conifers would have 38 times the flow resistance, making conifer-dominated ecosystems improbable in an angiosperm world.}, } @article {pmid16370324, year = {2006}, author = {Wartenberg, M and Dönmez, F and Budde, P and Sauer, H}, title = {Embryonic stem cells: a novel tool for the study of antiangiogenesis and tumor-induced angiogenesis.}, journal = {Handbook of experimental pharmacology}, volume = {}, number = {174}, pages = {53-71}, pmid = {16370324}, issn = {0171-2004}, mesh = {Angiogenesis Inhibitors/*pharmacology ; Animals ; Biomedical Research/*methods ; Humans ; Neoplasms/*blood supply/drug therapy ; *Neovascularization, Pathologic ; Research Embryo Creation ; Stem Cells/cytology/drug effects/*metabolism ; }, abstract = {Major research initiatives in antiangiogenesis research have been undertaken to control angiogenic diseases such as polyarthritis, psoriasis, endometriosis, and diabetic retinopathy, and inhibition of tumor-induced angiogenesis has emerged as one of the most promising anti-cancer therapies currently available. Although several quantitative in vivo (i.e., animal models) as well as in vitro (i.e., pure endothelial cell cultures) angiogenesis assays have been described, the development of novel angiogenesis assays with organotypic culture systems that take into account oxygen and nutrient gradients, depth-dependent changes in intracellular pH and a redox state similar to that found in a natural tissue microenvironment are necessary to investigate blood vessel growth. Embryonic stem cells of mouse and human origin have the capacity to develop into three-dimensional tissues with functional capillaries, and this model system represents an excellent in vitro model for antiangiogenesis research. Upon confrontation of stem cells by co-culture with multicellular tumor spheroids, tumor-induced angiogenesis, i.e., the invasion of endothelial host-derived cells into a tumor tissue, can also be monitored. The current review provides an overview of embryonic stem cells as novel tools for antiangiogenesis research and outlines the use of confrontation cultures for the study of tumor-induced angiogenesis.}, } @article {pmid16369939, year = {2006}, author = {Blackstone, NW}, title = {Multicellular redox regulation: integrating organismal biology and redox chemistry.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {28}, number = {1}, pages = {72-77}, doi = {10.1002/bies.20337}, pmid = {16369939}, issn = {0265-9247}, mesh = {Animals ; Biological Evolution ; Humans ; *Metabolism ; Mitochondria/*metabolism ; Oxidation-Reduction ; Reactive Oxygen Species/metabolism ; }, abstract = {Early in the 20th century, Charles Manning Child attributed organismal gradients in metabolism to interactions among groups of cells. Metabolic gradients are now firmly grounded in redox chemistry, yet modern work on metabolic signaling has consistently focused on the cellular level. Multicellular redox regulation, however, may occur when redox state is determined by the behavior of a group of cells. For instance, typically an abundance of substrate will shift the redox state of mitochondria in the direction of reduction, leading to increased reactive oxygen species (ROS). These ROS, in turn, may modify the conformation and activity of proteins involved in signaling pathways, resulting in phenotypic changes. In contrast, if substrate triggers the contractions of a muscular structure comprising mitochondrion-rich cells, the resulting metabolic demand may shift the redox state in the direction of oxidation, with a corresponding decrease of ROS and different phenotypic effects. Indeed, colonial hydroids exemplify this process. Parallel examples may occur whenever mitochondria are concentrated in cells of structures that can respond to environmental perturbations with increased metabolic demand. In these circumstances, predicting the direction of metabolic signaling may require an understanding of events at the organismal level.}, } @article {pmid16368776, year = {2006}, author = {Novinec, M and Kordis, D and Turk, V and Lenarcic, B}, title = {Diversity and evolution of the thyroglobulin type-1 domain superfamily.}, journal = {Molecular biology and evolution}, volume = {23}, number = {4}, pages = {744-755}, doi = {10.1093/molbev/msj082}, pmid = {16368776}, issn = {0737-4038}, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Expressed Sequence Tags/chemistry ; *Genetic Variation ; Humans ; Molecular Sequence Data ; *Multigene Family ; Protein Structure, Tertiary/genetics ; Thyroglobulin/chemistry/*classification/*genetics ; }, abstract = {Multidomain proteins are gaining increasing consideration for their puzzling, flexible utilization in nature. The presence of the characteristic thyroglobulin type-1 (Tg1) domain as a protein module in a variety of multicellular organisms suggests pivotal roles for this building block. To gain insight into the evolution of Tg1 domains, we performed searches of protein, expressed sequence tag, and genome databases. Tg1 domains were found to be Metazoa specific, and we retrieved a total of 170 Tg1 domain-containing protein sequences. Their architectures revealed a wide taxonomic distribution of proteins containing Tg1 domains followed or preceded by secreted protein, acidic, rich in cysteines (SPARC)-type extracellular calcium-binding domains. Other proteins contained lineage-specific domain combinations of peptidase inhibitory modules or domains with different biological functions. Phylogenetic analysis showed that Tg1 domains are highly conserved within protein structures, whereas insertion into novel proteins is followed by rapid diversification. Seven different basic types of protein architecture containing the Tg1 domain were identified in vertebrates. We examined the evolution of these protein groups by combining Tg1 domain phylogeny with additional analyses based on other characteristic domains. Testicans and secreted modular calcium binding protein (SMOCs) evolved from invertebrate homologs by introduction of vertebrate-specific domains, nidogen evolved by insertion of a Tg1 domain into a preexisting architecture, and the remaining four have unique architectures. Thyroglobulin, Trops, and the major histocompatibility complex class II-associated invariant chain are vertebrate specific, while an insulin-like growth factor-binding protein and nidogen were also identified in urochordates. Among vertebrates, we observed differences in protein repertoires, which result from gene duplication and domain duplication. Members of five groups have been characterized at the molecular level. All exhibit subtle differences in their specificities and function either as peptidase inhibitors (thyropins), substrates, or both. As far as the sequence is concerned, only a few conserved residues were identified. In combination with structural data, our analysis shows that the Tg1 domain fold is highly adaptive and comprises a relatively well-conserved core surrounded by highly variable loops that account for its multipurpose function in the animal kingdom.}, } @article {pmid16368151, year = {2006}, author = {Cooper, EL and Kvell, K and Engelmann, P and Nemeth, P}, title = {Still waiting for the toll?.}, journal = {Immunology letters}, volume = {104}, number = {1-2}, pages = {18-28}, doi = {10.1016/j.imlet.2005.11.012}, pmid = {16368151}, issn = {0165-2478}, mesh = {Animals ; Base Sequence ; Diptera/genetics/immunology ; Environmental Pollution ; Evolution, Molecular ; *Immunity, Innate ; Killer Cells, Natural/immunology ; Molecular Sequence Data ; Oligochaeta/genetics/*immunology ; Phagocytosis ; Toll-Like Receptors/genetics/*immunology ; }, abstract = {Multicellular organisms including invertebrates and vertebrates live in various habitats that may be aquatic or terrestrial where they are constantly exposed to deleterious pathogens. These include viruses, bacteria, fungi, and parasites. They have evolved various immunodefense mechanisms that may protect them from infection by these microorganisms. These include cellular and humoral responses and the level of differentiation of the response parallels the evolutionary development of the species. The first line of innate immunity in earthworms is the body wall that prevents the entrance of microbes into the coelomic cavity that contains fluid in which there are numerous leukocyte effectors of immune responses. When this first barrier is broken, a series of host responses is set into motion activating the leukocytes and the coelomic fluid. The responses are classified as innate, natural, non-specific, non-anticipatory, non-clonal (germ line) in contrast to the vertebrate capacity that is considered adaptive, induced, specific, anticipatory and clonal (somatic). Specific memory is associated with the vertebrate response and there is information that the innate response of invertebrates may under certain conditions possess specific memory. The invertebrate system when challenged affects phagocytosis, encapsulation, agglutination, opsonization, clotting and lysis. At least two major leukocytes, small and large mediate lytic reactions against several tumor cell targets. Destruction of tumor cells in vitro shows that phagocytosis and natural killer cell responses are distinct properties of these leukocytes. This has prompted newer searches for immune function and regulation in other systems. The innate immune system of the earthworm has been analyzed for more than 40 years with every aspect examined. However, there are no known entire sequences of the earthworm as exists in these other invertebrates. Because the earthworm lives in soil and has been utilized as a successful monitor for pollution, there are studies that reveal up and down regulation of responses in the immune system after exposure to a variety of environmental pollutants. Moreover, there are partial sequences that appear in earthworms after exposure to environmental pollutants such as cadmium and copper. There are now attempts to define the AHR receptor crucial for intracellular signaling after exposure to pollutants, but without linking the signals to changes in the immune system. There are several pathways for signal transduction, including JAK/STAT, TOLL, TRAF PIP3, known in invertebrates and vertebrates. For resistance to pathogens, conserved signal transduction components are required and these include a Toll/IL-1 receptor domain adaptor protein that functions upstream of a conserved p38 MAP kinase pathway. This pathway may be an ancestral innate immune signaling pathway found in a putative common ancestor of nematodes, arthropods and even vertebrates. It could also help us to link pollution, innate immunity and transduction in earthworms.}, } @article {pmid16367971, year = {2006}, author = {Hallmann, A}, title = {The pherophorins: common, versatile building blocks in the evolution of extracellular matrix architecture in Volvocales.}, journal = {The Plant journal : for cell and molecular biology}, volume = {45}, number = {2}, pages = {292-307}, doi = {10.1111/j.1365-313X.2005.02627.x}, pmid = {16367971}, issn = {0960-7412}, mesh = {Algal Proteins/chemistry/*physiology ; Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Western ; Chlamydomonas/genetics/*physiology ; DNA Primers ; Exons ; Extracellular Matrix ; Extracellular Matrix Proteins/chemistry/*physiology ; Glycoproteins/chemistry/*physiology ; Introns ; Molecular Sequence Data ; RNA, Messenger/genetics ; Sequence Homology, Amino Acid ; }, abstract = {Green algae of the order Volvocales provide an unrivalled opportunity for exploring the transition from unicellularity to multicellularity. They range from unicells, like Chlamydomonas, through homocytic colonial forms with increasing cooperation of individual cells, like Gonium or Pandorina, to heterocytic multicellular forms with different cell types and a complete division of labour, like Volvox. A fundamental requirement for the evolution of multicellularity is the development of a complex, multifunctional extracellular matrix (ECM). The ECM has many functions, which can change under developmental control or as a result of environmental factors. Here molecular data from 15 novel proteins are presented. These proteins have been identified in Chlamydomonas reinhardtii, Gonium pectorale, Pandorina morum and Volvox carteri, and all belong to a single protein family, the pherophorins. Pherophorin-V1 is shown to be a glycoprotein localized to the 'cellular zone' of the V. carteri ECM. Pherophorin-V1 and -V2 mRNAs are strongly induced not only by the sex inducer, which triggers sexual development at extremely low concentrations, but also by mechanical wounding. Like the extensins of higher plants, which are also developmentally controlled or sometimes inducible by wounding, the pherophorins contain a (hydroxy-)proline-rich (HR) rod-like domain and are abundant within the extracellular compartment. In contrast to most extensins, pherophorins have additional globular A and B domains on both ends of the HR domains. Therefore pherophorins most closely resemble a particular class of higher plant extensin, the solanaceous lectins (e.g. potato lectin), suggesting multivalent carbohydrate-binding functions are present within the A and B domains and are responsible for cross-linking. Our results suggest that pherophorins are used as the building blocks for the extracellular scaffold throughout the Volvocales, with the characteristic mesh sizes in different ECM structures being a result of the highly diverse extensions of the HR domains. Pherophorins have therefore been a versatile element during the evolution of ECM architecture in these green algae.}, } @article {pmid16365380, year = {2006}, author = {Liang, H and Landweber, LF}, title = {A genome-wide study of dual coding regions in human alternatively spliced genes.}, journal = {Genome research}, volume = {16}, number = {2}, pages = {190-196}, pmid = {16365380}, issn = {1088-9051}, support = {R01 GM059708/GM/NIGMS NIH HHS/United States ; GM59708/GM/NIGMS NIH HHS/United States ; }, mesh = {Alternative Splicing/*genetics ; Animals ; Codon, Terminator/genetics ; *Evolution, Molecular ; Exons ; Genome, Human/*genetics ; Humans ; Open Reading Frames/*genetics ; *Selection, Genetic ; }, abstract = {Alternative splicing is a major mechanism for gene product regulation in many multicellular organisms. By using different exon combinations, some coding regions can encode amino acids in multiple reading frames in different transcripts. Here we performed a systematic search through a set of high-quality human transcripts and show that approximately 7% of alternatively spliced genes contain dual (multiple) coding regions. By using a conservative criterion, we found that in these regions most secondary reading frames evolved recently in mammals, and a significant proportion of them may be specific to primates. Based on the presence of in-frame stop codons in orthologous sequences in other animals, we further classified ancestral and derived reading frames in these regions. Our results indicated that ancestral reading frames are usually under stronger selection than are derived reading frames. Ancestral reading frames mainly influence the coding properties of these dual coding regions. Compared with coding regions of the whole genome, ancestral reading frames largely maintain similar nucleotide composition at each codon position and amino acid usage, while derived reading frames are significantly different. Our results also indicated that prior to acquisition of a new reading frame, the suppression of in-frame stop codons in the ancestral state is mainly achieved by one-step transition substitutions at the first or second codon position. Finally, the selective forces imposed on these dual coding regions will also be discussed.}, } @article {pmid16352710, year = {2005}, author = {Gregor, T and Bialek, W and de Ruyter van Steveninck, RR and Tank, DW and Wieschaus, EF}, title = {Diffusion and scaling during early embryonic pattern formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {102}, number = {51}, pages = {18403-18407}, pmid = {16352710}, issn = {0027-8424}, support = {P50 GM071508/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Body Patterning ; Diffusion ; Drosophila melanogaster/*embryology/genetics ; Embryo, Nonmammalian/*embryology ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; }, abstract = {Development of spatial patterns in multicellular organisms depends on gradients in the concentration of signaling molecules that control gene expression. In the Drosophila embryo, Bicoid (Bcd) morphogen controls cell fate along 70% of the anteroposterior axis but is translated from mRNA localized at the anterior pole. Gradients of Bcd and other morphogens are thought to arise through diffusion, but this basic assumption has never been rigorously tested in living embryos. Furthermore, because diffusion sets a relationship between length and time scales, it is hard to see how patterns of gene expression established by diffusion would scale proportionately as egg size changes during evolution. Here, we show that the motion of inert molecules through the embryo is well described by the diffusion equation on the relevant length and time scales, and that effective diffusion constants are essentially the same in closely related dipteran species with embryos of very different size. Nonetheless, patterns of gene expression in these different species scale with egg length. We show that this scaling can be traced back to scaling of the Bcd gradient itself. Our results, together with constraints imposed by the time scales of development, suggest that the mechanism for scaling is a species-specific adaptation of the Bcd lifetime.}, } @article {pmid16341072, year = {2005}, author = {Martindale, MQ}, title = {The evolution of metazoan axial properties.}, journal = {Nature reviews. Genetics}, volume = {6}, number = {12}, pages = {917-927}, doi = {10.1038/nrg1725}, pmid = {16341072}, issn = {1471-0056}, mesh = {Animals ; Body Patterning/*genetics ; Cell Differentiation/*genetics ; Gene Expression Regulation, Developmental/*genetics ; Invertebrates/*anatomy & histology/*genetics ; *Phylogeny ; }, abstract = {Renewed interest in the developmental basis of organismal complexity, and the emergence of new molecular tools, is improving our ability to study the evolution of metazoan body plans. The most substantial changes in body-plan organization occurred early in metazoan evolution; new model systems for studying basal metazoans are now being developed, and total-genome-sequencing initiatives are underway for at least three of the four most important taxa. The elucidation of how the gene networks that are involved in axial organization, germ-layer formation and cell differentiation are used differently during development is generating a more detailed understanding of the events that have led to the current diversity of multicellular life.}, } @article {pmid16338359, year = {2005}, author = {Hirano, Y and Murata, S and Tanaka, K}, title = {Large- and small-scale purification of mammalian 26S proteasomes.}, journal = {Methods in enzymology}, volume = {399}, number = {}, pages = {227-240}, doi = {10.1016/S0076-6879(05)99015-0}, pmid = {16338359}, issn = {0076-6879}, mesh = {Animals ; Cell Nucleus/enzymology ; Chromatography, Affinity ; Electrophoresis, Gel, Two-Dimensional ; Mammals ; Proteasome Endopeptidase Complex/*isolation & purification ; Rats ; }, abstract = {The 26S proteasome is an ATP-dependent protease known to collaborate with ubiquitin, whose polymerization acts as a marker for regulated and enforced destruction of unnecessary proteins in eukaryotic cells. It is an unusually large multi-subunit protein complex, consisting of a central catalytic machine (called the 20S proteasome or CP/core particle) and two terminal regulatory subcomplexes, termed PA700 or RP/regulatory particle, that are attached to both ends of the central portion in opposite orientations to form an enzymatically active proteasome. To date, proteolysis driven by the ubiquitin-proteasome system has been shown to be involved in a diverse array of biologically important processes, such as the cell cycle, immune response, signaling cascades, and developmental programs; and the field continues to expand rapidly. Whereas the proteasome complex has been highly conserved during evolution because of its fundamental roles in cells, it has also acquired considerable diversity in multicellular organisms, particularly in mammals, such as immunoproteasomes, PA28, S5b, and various alternative splicing forms of S5a (Rpm 10). However, the details of the ultimate pathophysiological roles of mammalian proteasomes have remained elusive. This article focuses on methods for assay and purification of 26S proteasomes from mammalian cells and tissues.}, } @article {pmid16323046, year = {2005}, author = {Bonatto, D and Brendel, M and Henriques, JA}, title = {In silico identification and analysis of new Artemis/Artemis-like sequences from fungal and metazoan species.}, journal = {The protein journal}, volume = {24}, number = {6}, pages = {399-411}, pmid = {16323046}, issn = {1572-3887}, mesh = {Amino Acid Sequence ; Animals ; Cluster Analysis ; Computational Biology ; DNA Damage ; DNA-Binding Proteins ; Endodeoxyribonucleases ; Endonucleases ; Fungal Proteins ; Humans ; *Models, Molecular ; Nuclear Proteins/chemistry/*genetics ; Phylogeny ; Recombination, Genetic ; Saccharomyces cerevisiae Proteins ; }, abstract = {The Artemis Group comprises mammalian proteins with important functions in the repair of ionizing radiation-induced DNA double-strand breaks and in the cleavage of DNA hairpin extremities generated during V(D)J recombination. Little is known about the presence of Artemis/Artemis-like proteins in non-mammalian species. We have characterized new Artemis/Artemis-like sequences from the genomes of some fungi and from non-mammalian metazoan species. An in-depth phylogenetic analysis of these new Artemis/Artemis-like sequences showed that they form a distinct clade within the Pso2p/Snm1p A and B Groups. Hydrophobic cluster analysis and three-dimensional modeling allowed to map and to compare conserved regions in these Artemis/Artemis-like proteins. The results indicate that Artemis probably belongs to an ancient DNA recombination mechanism that diversified with the evolution of multi-cellular eukaryotic lineage.}, } @article {pmid16310746, year = {2005}, author = {Skovgaard, A and Massana, R and Balagué, V and Saiz, E}, title = {Phylogenetic position of the copepod-infesting parasite Syndinium turbo (Dinoflagellata, Syndinea).}, journal = {Protist}, volume = {156}, number = {4}, pages = {413-423}, doi = {10.1016/j.protis.2005.08.002}, pmid = {16310746}, issn = {1434-4610}, mesh = {Animals ; Copepoda/*parasitology ; DNA, Intergenic/analysis/genetics ; Dinoflagellida/*classification/genetics ; Molecular Sequence Data ; Phylogeny ; RNA, Ribosomal/*analysis ; RNA, Ribosomal, 5.8S/genetics ; Sequence Analysis, DNA ; }, abstract = {Sequences were determined for the nuclear-encoded small subunit (SSU) rRNA and 5.8S rRNA genes as well as the internal transcribed spacers ITS1 and ITS2 of the parasitic dinoflagellate genus Syndinium from two different marine copepod hosts. Syndinium developed a multicellular plasmodium inside its host and at maturity free-swimming zoospores were released. Syndinium plasmodia in the copepod Paracalanus parvus produced zoospores of three different morphological types. However, full SSU rDNA sequences for the three morphotypes were 100% identical and also their ITS1-ITS2 sequences were identical except for four base pairs. It was concluded that the three morphotypes belong to a single species that was identified as Syndinium turbo, the type species of the dinoflagellate subdivision Syndinea. The SSU rDNA sequence of another Syndinium species infecting Corycaeus sp. was similar to Syndinium turbo except for three base pairs and the ITS1-ITS2 sequences of the two species differed at 34-35 positions. Phylogenetic analyses placed Syndinium as a sister taxon to the blue crab parasite Hematodinium sp. and both parasites were affiliated with the so-called marine alveolate Group II. This corroborates the hypothesis that marine alveolate Group II is Syndinea.}, } @article {pmid16300654, year = {2005}, author = {Pilkington, GJ}, title = {Cancer stem cells in the mammalian central nervous system.}, journal = {Cell proliferation}, volume = {38}, number = {6}, pages = {423-433}, pmid = {16300654}, issn = {0960-7722}, mesh = {Animals ; Central Nervous System Neoplasms/*pathology ; Humans ; Neoplastic Stem Cells/*pathology/physiology ; }, abstract = {Malignant tumours intrinsic to the central nervous system (CNS) are among the most difficult of neoplasms to treat effectively. The major biological features of these tumours that preclude successful therapy include their cellular heterogeneity, which renders them highly resistant to both chemotherapy and radiotherapy, and the propensity of the component tumour cells to invade, diffusely, the contiguous nervous tissues. The tumours are classified according to perceived cell of origin, gliomas being the most common generic group. In the 1970s transplacental administration of the potent neurocarcinogen, N-ethyl-N-nitrosourea (ENU), enabled investigation of the sequential development of brain and spinal neoplasms by electron microscopy and immunohistochemistry. The significance of the primitive cells of the subependymal plate in cellular origin and evolution of a variety of glial tumours was thereby established. Since then, the development of new cell culture methods, including the in vitro growth of neurospheres and multicellular tumour spheroids, and new antigenic markers of stem cells and glial/neuronal cell precursor cells, including nestin, Mushashi-1 and CD133, have led to a reappraisal of the histological classification and origins of CNS tumours. Moreover, neural stem cells may also provide new vectors in exciting novel therapeutic strategies for these tumours. In addition to the gliomas, stem cells may have been identified in paediatric tumours including cerebellar medulloblastoma, thought to be of external granule cell neuronal derivation. Interestingly, while the stem cell marker CD133 is expressed in these primitive neuroectodermal tumours (PNETs), the chondroitin sulphate proteoglycan neuronal/glial 2 (NG2), which appears to denote increased proliferative, but reduced migratory activity in adult gliomas, is rarely expressed. This is in contrast to the situation in the histologically similar supratentorial PNETs. A possible functional 'switch' between proliferation and migration in developing neural tumour cells may exist between NG2 and ganglioside GD3. The divergent pathways of differentiation of CNS tumours and the possibility of stem cell origin, for some, if not all, such neoplasms remain a matter for debate and continued research, but the presence of self-renewing neural stem cells in the CNS of both children and adults strongly suggests a role for these cells in tumour initiation and resistance to current therapeutic strategies.}, } @article {pmid16299590, year = {2005}, author = {Sperisen, P and Schmid, CD and Bucher, P and Zilian, O}, title = {Stealth proteins: in silico identification of a novel protein family rendering bacterial pathogens invisible to host immune defense.}, journal = {PLoS computational biology}, volume = {1}, number = {6}, pages = {e63}, pmid = {16299590}, issn = {1553-7358}, mesh = {Amino Acid Sequence ; Animals ; Bacteria/chemistry/genetics/*immunology/*pathogenicity ; Bacterial Infections/*immunology/microbiology ; *Computational Biology ; Conserved Sequence ; Evolution, Molecular ; Genome/genetics ; Humans ; Molecular Sequence Data ; Phylogeny ; Proteins/chemistry/*classification/genetics/*immunology ; Sequence Alignment ; Streptomyces coelicolor/genetics ; Virulence Factors ; }, abstract = {There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC) is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.}, } @article {pmid16297386, year = {2005}, author = {Iliev, DB and Roach, JC and Mackenzie, S and Planas, JV and Goetz, FW}, title = {Endotoxin recognition: in fish or not in fish?.}, journal = {FEBS letters}, volume = {579}, number = {29}, pages = {6519-6528}, pmid = {16297386}, issn = {0014-5793}, support = {K08 AI056092/AI/NIAID NIH HHS/United States ; 5K08AI056092/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Endotoxins/*immunology/pharmacology ; Fishes/*immunology ; Phagocytes/drug effects ; Receptors, Pattern Recognition/*immunology ; Toll-Like Receptors/genetics/immunology ; }, abstract = {The interaction between pathogens and their multicellular hosts is initiated by activation of pathogen recognition receptors (PRRs). These receptors, that include most notably members of the toll-like receptor (TLR) family, recognize specific pathogen-associated molecular patterns (PAMPs). TLR4 is a central part of the receptor complex that is involved in the activation of the immune system by lipopolysaccharide (LPS) through the specific recognition of its endotoxic moiety (Lipid A). This is a critical event that is essential for the immune response to Gram-negative bacteria as well as the etiology of endotoxic shock. Interestingly, compared to mammals, fish are resistant to endotoxic shock. This in vivo resistance concurs with in vitro studies demonstrating significantly lowered sensitivity of fish leukocytes to LPS activation. Further, our in vitro analyses demonstrate that in trout mononuclear phagocytes, LPS fails to induce antiviral genes, an event that occurs downstream of TLR4 and is required for the development of endotoxic shock. Finally, an in silico approach that includes mining of different piscine genomic and EST databases, reveals the presence in fish of all of the major TLR signaling elements except for the molecules specifically involved in TLR4-mediated endotoxin recognition and signaling in mammals. Collectively, our analysis questions the existence of TLR4-mediated cellular responses to LPS in fish. We further speculate that other receptors, in particular beta-2 integrins, may play a primary role in the activation of piscine leukocytes by LPS.}, } @article {pmid16295520, year = {2005}, author = {Schuiling, GA}, title = {On sexual behavior and sex-role reversal.}, journal = {Journal of psychosomatic obstetrics and gynaecology}, volume = {26}, number = {3}, pages = {217-223}, doi = {10.1080/01674820500170000}, pmid = {16295520}, issn = {0167-482X}, mesh = {Animals ; Courtship/psychology ; Female ; *Gender Identity ; Homosexuality, Female/*psychology ; Humans ; Male ; Medicine in Literature ; Poetry as Topic ; Reproduction ; *Sexual Behavior ; Sexual Behavior, Animal ; Social Dominance ; Species Specificity ; }, abstract = {Sex is not about reproduction; sex is about (re-)combination of DNA. Sex, not reproduction, always involves physical contact between two individuals; to achieve this, strategies of sexual behavior evolved. Sexual behavior, therefore, did not evolve as part of a reproductive strategy, but evolved to enable exchange of genetic material. In multicellular organisms the situation is more complicated than in unicellular organisms, as it is impossible for each cell within a multicellular body to have sex with another cell. Hence, evolution selected a system in which the possibility to have sex was limited to only one cell-line: the germ cells. As a result, sex adopted the character of fertilization, and sex and reproduction became inseparably linked. Still, in some species, including humans, sexual behavior still exhibits features of its evolutionary past: in humans (like in bonobo's) most sexual activity and many sexual behavioral patterns have nothing to do with reproduction (masturbation, homosexual behavior, for example); in humans, sexual behavior also became associated with other strategic objectives, such as intensifying the pair bond, expression of love or power. Different genders - male and female - evolved, and each gender evolved typical gender-related sexual and reproductive strategies as well. In most multicellular species, these strategies became inextricably mixed, and sexual behavior increasingly more - and in most species even exclusively - 'served' the interests of reproduction: sexual behavior became more or less synonymous with reproductive behavior. In most species, the 'mix' of sexual and reproductive strategies evolved into typical gender-related patterns of behavior, that is, in typical 'sex-roles'. Often, males are bigger and more 'beautiful' (= more intensely ornamented) than females; males compete with each other for access to females; males court females, while females choose males ('female choice'). However, ecological circumstances may cause a reversal of sex-roles, resulting in a situation in which females are bigger and more intensely ornamented than males, females compete for access to males, females court males and only males invest in care for the young, provided they are relatively certain of their paternity. Also, as in the case of the spotted hyena, females may be highly virilized and be socially dominant. This 'sex-role reversal' is seen, e.g., when males are relatively rare due to high predation pressure, or when the process of reproduction is very risky for the same reason: then it is 'better' that males, with their plenty of sperm, are wasted, than females with their few, precious eggs. It can be argued, with women being the fair sex, exhibiting competitive behavior and with an actively displaying courtship, and with men investing heavily in their offspring, meanwhile taking all (cultural) kinds of measures to guarantee their paternity, that humans, too, exhibit some degree of sex-role reversal.}, } @article {pmid16288838, year = {2006}, author = {Rodríguez-Trelles, F and Tarrío, R and Ayala, FJ}, title = {Models of spliceosomal intron proliferation in the face of widespread ectopic expression.}, journal = {Gene}, volume = {366}, number = {2}, pages = {201-208}, doi = {10.1016/j.gene.2005.09.004}, pmid = {16288838}, issn = {0378-1119}, mesh = {Animals ; Evolution, Molecular ; Gene Expression Regulation/*genetics ; Humans ; Introns/*genetics ; RNA Precursors/*genetics ; RNA Splicing/*genetics ; Spliceosomes/*genetics ; Transcription, Genetic/*genetics ; }, abstract = {It is now certain that today living organisms can acquire new spliceosomal introns in their genes. The proposed sources of spliceosomal introns are exons, transposons, and other introns, including spliceosomal and group II self-splicing introns. Spliceosomal introns are thought to be the most likely source, because the inserted sequence would immediately be endowed with the essential set of intron recognition sequences, thereby preventing the deleterious effects associated with incorrect splicing. The most obvious spliceosomal intron duplication pathways involve an RNA transcript intermediate step. Therefore, for a spliceosomal intron to be originated by duplication, either the source gene from which the novel intron is derived, or that gene and the recipient gene, which contains the novel intron, would need to be expressed in the germ line. Intron proliferation surveys indicate that putative intron duplicate-containing genes do not always match detectable expression in the germ line, which casts doubt on the generality of the duplication model. However, judging mechanisms of intron gain (or loss) from present-day gene expression profiles could be erroneous, if expression patterns were different at the time the introns arose. In fact, this may likely be so in most cases. Ectopic expression, i.e., the expression of genes at times and locations where the target gene is not known to have a function, is a much more common phenomenon than previously realized. We conclude with a speculation on a possible interplay between spliceosomal introns and ectopic expression at the origin of multicellularity.}, } @article {pmid16288782, year = {2006}, author = {Michod, RE and Viossat, Y and Solari, CA and Hurand, M and Nedelcu, AM}, title = {Life-history evolution and the origin of multicellularity.}, journal = {Journal of theoretical biology}, volume = {239}, number = {2}, pages = {257-272}, doi = {10.1016/j.jtbi.2005.08.043}, pmid = {16288782}, issn = {0022-5193}, mesh = {Animals ; *Biological Evolution ; Body Size ; Cell Differentiation ; Cell Division ; Cell Survival ; Chlorophyta/*cytology ; *Models, Biological ; Models, Genetic ; Reproduction ; Selection, Genetic ; }, abstract = {The fitness of an evolutionary individual can be understood in terms of its two basic components: survival and reproduction. As embodied in current theory, trade-offs between these fitness components drive the evolution of life-history traits in extant multicellular organisms. Here, we argue that the evolution of germ-soma specialization and the emergence of individuality at a new higher level during the transition from unicellular to multicellular organisms are also consequences of trade-offs between the two components of fitness-survival and reproduction. The models presented here explore fitness trade-offs at both the cell and group levels during the unicellular-multicellular transition. When the two components of fitness negatively covary at the lower level there is an enhanced fitness at the group level equal to the covariance of components at the lower level. We show that the group fitness trade-offs are initially determined by the cell level trade-offs. However, as the transition proceeds to multicellularity, the group level trade-offs depart from the cell level ones, because certain fitness advantages of cell specialization may be realized only by the group. The curvature of the trade-off between fitness components is a basic issue in life-history theory and we predict that this curvature is concave in single-celled organisms but becomes increasingly convex as group size increases in multicellular organisms. We argue that the increasingly convex curvature of the trade-off function is driven by the initial cost of reproduction to survival which increases as group size increases. To illustrate the principles and conclusions of the model, we consider aspects of the biology of the volvocine green algae, which contain both unicellular and multicellular members.}, } @article {pmid16280547, year = {2006}, author = {Lynch, M}, title = {The origins of eukaryotic gene structure.}, journal = {Molecular biology and evolution}, volume = {23}, number = {2}, pages = {450-468}, doi = {10.1093/molbev/msj050}, pmid = {16280547}, issn = {0737-4038}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; GM36827/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Eukaryotic Cells ; *Evolution, Molecular ; Genome/*genetics ; Humans ; Mutation ; RNA Splicing/genetics ; RNA, Messenger/genetics ; Recombination, Genetic ; Selection, Genetic ; }, abstract = {Most of the phenotypic diversity that we perceive in the natural world is directly attributable to the peculiar structure of the eukaryotic gene, which harbors numerous embellishments relative to the situation in prokaryotes. The most profound changes include introns that must be spliced out of precursor mRNAs, transcribed but untranslated leader and trailer sequences (untranslated regions), modular regulatory elements that drive patterns of gene expression, and expansive intergenic regions that harbor additional diffuse control mechanisms. Explaining the origins of these features is difficult because they each impose an intrinsic disadvantage by increasing the genic mutation rate to defective alleles. To address these issues, a general hypothesis for the emergence of eukaryotic gene structure is provided here. Extensive information on absolute population sizes, recombination rates, and mutation rates strongly supports the view that eukaryotes have reduced genetic effective population sizes relative to prokaryotes, with especially extreme reductions being the rule in multicellular lineages. The resultant increase in the power of random genetic drift appears to be sufficient to overwhelm the weak mutational disadvantages associated with most novel aspects of the eukaryotic gene, supporting the idea that most such changes are simple outcomes of semi-neutral processes rather than direct products of natural selection. However, by establishing an essentially permanent change in the population-genetic environment permissive to the genome-wide repatterning of gene structure, the eukaryotic condition also promoted a reliable resource from which natural selection could secondarily build novel forms of organismal complexity. Under this hypothesis, arguments based on molecular, cellular, and/or physiological constraints are insufficient to explain the disparities in gene, genomic, and phenotypic complexity between prokaryotes and eukaryotes.}, } @article {pmid16272131, year = {2005}, author = {Aono, N and Inoue, T and Shiraishi, H}, title = {Genes specifically expressed in sexually differentiated female spheroids of Volvox carteri.}, journal = {Journal of biochemistry}, volume = {138}, number = {4}, pages = {375-382}, doi = {10.1093/jb/mvi139}, pmid = {16272131}, issn = {0021-924X}, mesh = {Amino Acid Sequence ; Base Sequence ; Biological Evolution ; DNA, Complementary/isolation & purification ; Extracellular Matrix ; *Gene Expression Regulation, Plant ; *Genes, Plant ; Molecular Sequence Data ; RNA, Messenger/metabolism ; Reproduction ; Sequence Analysis, DNA ; Volvox/*genetics/growth & development ; }, abstract = {Volvox carteri is a multicellular green alga with only two cell types, somatic cells and reproductive cells. Phylogenetic analysis suggests that this organism has evolved from a Chlamydomonas-like unicellular ancestor along with multicellularity, cellular differentiation, and a change in the mode of sexual reproduction from isogamy to oogamy. To examine the mechanism of sexual differentiation and the evolution of oogamy, we isolated 6 different cDNA sequences specifically expressed in sexually differentiated female spheroids. The genes for the cDNAs were designated SEF1 to SEF6. The time course of accumulation of each mRNA was shown to be distinct. The expression of some of these genes was not significantly affected when the sexual inducer was removed after the induction of sexual development. Sequence analysis indicates that SEF5 and SEF6 encode pherophorin-related proteins. Of these, SEF5 has the unique structural feature of a polyproline stretch in the C-terminal domain in addition to the one found in the central region.}, } @article {pmid16267011, year = {2005}, author = {Persaud, R and Zhou, H and Baker, SE and Hei, TK and Hall, EJ}, title = {Assessment of low linear energy transfer radiation-induced bystander mutagenesis in a three-dimensional culture model.}, journal = {Cancer research}, volume = {65}, number = {21}, pages = {9876-9882}, pmid = {16267011}, issn = {0008-5472}, support = {P01 CA049062/CA/NCI NIH HHS/United States ; R01 ES011804/ES/NIEHS NIH HHS/United States ; CA49062/CA/NCI NIH HHS/United States ; ES 11804/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; CHO Cells ; Cell Communication/*genetics/*radiation effects ; Cell Culture Techniques ; Cell Separation/methods ; Cricetinae ; Gap Junctions/genetics/radiation effects ; Humans ; Hybrid Cells ; Linear Energy Transfer ; Magnetics ; Mutagenesis/*radiation effects ; Reactive Oxygen Species/metabolism ; Thymine Nucleotides/metabolism ; Tritium ; }, abstract = {A three-dimensional cell culture model composed of human-hamster hybrid (A(L)) and Chinese hamster ovary (CHO) cells in multicellular clusters was used to investigate low linear energy transfer (LET) radiation-induced bystander genotoxicity. CHO cells were mixed with A(L) cells in a 1:5 ratio and briefly centrifuged to produce a spheroid of 4 x 10(6) cells. CHO cells were labeled with tritiated thymidine ([3H]dTTP) for 12 hours and subsequently incubated with A(L) cells for 24 hours at 11 degrees C. The short-range beta-particles emitted by [3H]dTTP result in self-irradiation of labeled CHO cells; thus, biological effects on neighboring A(L) cells can be attributed to the bystander response. Nonlabeled bystander A(L) cells were isolated from among labeled CHO cells by using a magnetic separation technique. Treatment of CHO cells with 100 microCi [3H]dTTP resulted in a 14-fold increase in bystander mutation incidence among neighboring A(L) cells compared with controls. Multiplex PCR analysis revealed the types of mutants to be significantly different from those of spontaneous origin. The free radical scavenger DMSO or the gap junction inhibitor Lindane within the clusters significantly reduced the mutation incidence. The use of A(L) cells that are dominant negative for connexin 43 and lack gap junction formation produced a complete attenuation of the bystander mutagenic response. These data provide evidence that low LET radiation can induce bystander mutagenesis in a three-dimensional model and that reactive oxygen species and intercellular communication may have a modulating role. The results of this study will address the relevant issues of actual target size and radiation quality and are likely to have a significant effect on our current understanding of radiation risk assessment.}, } @article {pmid16266279, year = {2005}, author = {Lichtenstein, AV}, title = {Cancer as a programmed death of an organism.}, journal = {Biochemistry. Biokhimiia}, volume = {70}, number = {9}, pages = {1055-1064}, doi = {10.1007/s10541-005-0224-y}, pmid = {16266279}, issn = {0006-2979}, mesh = {Alleles ; Animals ; *Apoptosis ; Evolution, Molecular ; Humans ; Mutagenesis ; Neoplasms/*genetics ; }, abstract = {The hypothesis introduces the idea that there is a critical level of mutagenesis that triggers a program of organism death by means of proliferation of killer cells. Similarly to apoptosis, which is an altruistic suicidal act of a faulty cell threatening the stability of a multicellular organism, a malignant tumor is an altruistic suicide of an individual carrier of harmful alleles threatening genetic stability of the population.}, } @article {pmid16266265, year = {2005}, author = {Morgunkova, AA}, title = {The p53 gene family: control of cell proliferation and developmental programs.}, journal = {Biochemistry. Biokhimiia}, volume = {70}, number = {9}, pages = {955-971}, doi = {10.1007/s10541-005-0210-4}, pmid = {16266265}, issn = {0006-2979}, mesh = {Animals ; *Cell Proliferation ; DNA-Binding Proteins/genetics/metabolism ; Embryonic Development/*genetics ; Genes, Tumor Suppressor ; Humans ; Mice ; Mice, Knockout ; Models, Biological ; Multigene Family ; Nuclear Proteins/genetics/metabolism ; Phosphoproteins/genetics/metabolism ; Trans-Activators/genetics/metabolism ; Tumor Protein p73 ; Tumor Suppressor Protein p53/*genetics/physiology ; Tumor Suppressor Proteins ; }, abstract = {For a quarter of a century the gene p53 has attracted close attention of scientists who deal with problems of carcinogenesis and maintenance of genetic stability. Multicellular organisms on our planet owe their rich evolution in many respects to the ability of this gene to protect cells from oncogenic transformation and harmful changes in DNA. A relatively recent discovery of structural p53 homologs, the genes p63 and p73, which seem to have more ancient roots, has roused keen interest in their function. Do they carry out oncosuppressor functions in partnership with p53 or do they possess their own specific functions? This review analyzes data on p53, p63, and p73 functional activity at the levels of the molecule, cell, and whole organism with the accent on examination of specific p63/p73 targets indicating a unique role of these genes in control of developmental processes.}, } @article {pmid16249258, year = {2006}, author = {Amikam, D and Galperin, MY}, title = {PilZ domain is part of the bacterial c-di-GMP binding protein.}, journal = {Bioinformatics (Oxford, England)}, volume = {22}, number = {1}, pages = {3-6}, doi = {10.1093/bioinformatics/bti739}, pmid = {16249258}, issn = {1367-4803}, support = {//Intramural NIH HHS/United States ; }, mesh = {Alginates/chemistry ; Amino Acid Sequence ; Bacterial Proteins/chemistry ; Carrier Proteins/*chemistry ; Computational Biology/*methods ; Cyclic GMP/*analogs & derivatives/chemistry ; Escherichia coli Proteins/chemistry ; *Gene Expression Regulation, Bacterial ; Genome, Bacterial ; Glucosyltransferases/chemistry ; Intracellular Signaling Peptides and Proteins/*chemistry ; Molecular Sequence Data ; Movement ; Phylogeny ; Polysaccharides/chemistry ; Protein Structure, Tertiary ; Proteins ; Pseudomonas aeruginosa/metabolism ; Second Messenger Systems ; }, abstract = {Recent studies identified c-di-GMP as a universal bacterial secondary messenger regulating biofilm formation, motility, production of extracellular polysaccharide and multicellular behavior in diverse bacteria. However, except for cellulose synthase, no protein has been shown to bind c-di-GMP and the targets for c-di-GMP action remain unknown. Here we report identification of the PilZ ("pills") domain (Pfam domain PF07238) in the sequences of bacterial cellulose synthases, alginate biosynthesis protein Alg44, proteins of enterobacterial YcgR and firmicute YpfA families, and other proteins encoded in bacterial genomes and present evidence indicating that this domain is (part of) the long-sought c-di-GMP-binding protein. Association of the PilZ domain with a variety of other domains, including likely components of bacterial multidrug secretion system, could provide clues to multiple functions of the c-di-GMP in bacterial pathogenesis and cell development.}, } @article {pmid16248676, year = {2005}, author = {Fiegna, F and Velicer, GJ}, title = {Exploitative and hierarchical antagonism in a cooperative bacterium.}, journal = {PLoS biology}, volume = {3}, number = {11}, pages = {e370}, pmid = {16248676}, issn = {1545-7885}, mesh = {Animals ; *Bacterial Physiological Phenomena ; Bacterial Proteins ; Binding, Competitive ; Biological Evolution ; Competitive Behavior ; Dictyostelium/metabolism ; Drug Resistance ; Gene Expression Regulation, Bacterial ; Genes, Dominant ; Genotype ; Molecular Sequence Data ; Myxococcales ; Myxococcus xanthus/metabolism ; Phenotype ; Social Behavior ; Social Dominance ; Spores, Bacterial ; }, abstract = {Social organisms that cooperate with some members of their own species, such as close relatives, may fail to cooperate with other genotypes of the same species. Such noncooperation may take the form of outright antagonism or social exploitation. Myxococcus xanthus is a highly social prokaryote that cooperatively develops into spore-bearing, multicellular fruiting bodies in response to starvation. Here we have characterized the nature of social interactions among nine developmentally proficient strains of M. xanthus isolated from spatially distant locations. Strains were competed against one another in all possible pairwise combinations during starvation-induced development. In most pairings, at least one competitor exhibited strong antagonism toward its partner and a majority of mixes showed bidirectional antagonism that decreased total spore production, even to the point of driving whole populations to extinction. Differential response to mixing was the primary determinant of competitive superiority rather than the sporulation efficiencies of unmixed populations. In some competitive pairings, the dominant partner sporulated more efficiently in mixed populations than in clonal isolation. This finding represents a novel form of exploitation in bacteria carried out by socially competent genotypes and is the first documentation of social exploitation among natural bacterial isolates. Patterns of antagonistic superiority among these strains form a highly linear dominance hierarchy. At least some competition pairs construct chimeric, rather than segregated, fruiting bodies. The cooperative prokaryote M. xanthus has diverged into a large number of distinct social types that cooperate with clone-mates but exhibit intense antagonism toward distinct social types of the same species. Most lengthy migration events in nature may thus result in strong antagonism between migratory and resident populations, and this antagonism may have large effects on local population sizes and dynamics. Intense mutual antagonism appears to be more prevalent in this prokaryotic social species than has been observed in the eukaryotic social slime mold Dictyostelium discoideum, which also exhibits multicellular development. The finding of several cases of facultative social exploitation among these natural isolates suggests that such exploitation may occur frequently in nature in many prokaryotes with cooperative traits.}, } @article {pmid16242907, year = {2005}, author = {Huang, S and Yuan, S and Dong, M and Su, J and Yu, C and Shen, Y and Xie, X and Yu, Y and Yu, X and Chen, S and Zhang, S and Pontarotti, P and Xu, A}, title = {The phylogenetic analysis of tetraspanins projects the evolution of cell-cell interactions from unicellular to multicellular organisms.}, journal = {Genomics}, volume = {86}, number = {6}, pages = {674-684}, doi = {10.1016/j.ygeno.2005.08.004}, pmid = {16242907}, issn = {0888-7543}, mesh = {Amoeba/genetics ; Animals ; Base Sequence ; Chordata, Nonvertebrate/genetics ; Cloning, Molecular ; Computational Biology ; *Evolution, Molecular ; Fungi/genetics ; Gene Library ; *Genetic Variation ; Humans ; Invertebrates/genetics ; Membrane Proteins/classification/*genetics ; *Models, Molecular ; Molecular Sequence Data ; Multigene Family/*genetics ; *Phylogeny ; Plants/genetics ; Sequence Analysis, DNA ; Species Specificity ; Tetraspanins ; Vertebrates/genetics ; }, abstract = {In animals, the tetraspanins are a large superfamily of membrane proteins that play important roles in organizing various cell-cell and matrix-cell interactions and signal pathways based on such interactions. However, their origin and evolution largely remain elusive and most of the family's members are functionally unknown or less known due to difficulties of study, such as functional redundancy. In this study, we rebuilt the family's phylogeny with sequences retrieved from online databases and our cDNA library of amphioxus. We reveal that, in addition to in metazoans, various tetraspanins are extensively expressed in protozoan amoebae, fungi, and plants. We also discuss the structural evolution of tetraspanin's major extracellular domain and the relation between tetraspanin's duplication and functional redundancy. Finally, we elucidate the coevolution of tetraspanins and eukaryotes and suggest that tetraspanins play important roles in the unicell-to-multicell transition. In short, the study of tetraspanin in a phylogenetic context helps us understand the evolution of intercellular interactions.}, } @article {pmid16237829, year = {2004}, author = {Tairbekov, MG}, title = {Mechanisms of the gravitational sensitivity of cells.}, journal = {Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology}, volume = {11}, number = {2}, pages = {P181-3}, pmid = {16237829}, issn = {1077-9248}, mesh = {Animals ; Cell Division/*physiology ; *Cell Physiological Phenomena ; Cells, Cultured ; Centrifugation ; Ciliophora/physiology ; Culture Media ; Eukaryota/physiology ; Fibroblasts ; *Gravitation ; Gravity Sensing ; Homeostasis/physiology ; Hypergravity ; Osteoblasts ; Rotation ; *Space Flight ; *Weightlessness ; Weightlessness Simulation ; }, abstract = {It is well known that specialized gravireceptory cells have been formed in the course of evolution in the majority of multicellular organisms. These are statosytes (statenchyme cells) in higher plants and otolith apparatus cells in animals. The mechanisms of gravity reception and the generation of gravitational stimuli in these cells are well understood. Therefore, our attention was focused on cells devoid of special gravireceptory mechanisms, namely cell cultures grown in vitro (fibroblasts and osteoblasts) and unicellular free-swimming (i.e. possessing a locomotor apparatus) organisms. These were mainly representatives of two classes: Ciliata and Flagellata. The choice of the objects of study was mainly determined by their ecological and physiological characteristics with the main goals of this work.}, } @article {pmid16234241, year = {2005}, author = {Noguchi, M and Takata, T and Kimura, Y and Manno, A and Murakami, K and Koike, M and Ohizumi, H and Hori, S and Kakizuka, A}, title = {ATPase activity of p97/valosin-containing protein is regulated by oxidative modification of the evolutionally conserved cysteine 522 residue in Walker A motif.}, journal = {The Journal of biological chemistry}, volume = {280}, number = {50}, pages = {41332-41341}, doi = {10.1074/jbc.M509700200}, pmid = {16234241}, issn = {0021-9258}, mesh = {Adaptor Proteins, Vesicular Transport ; Adenosine Triphosphatases ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Cell Cycle Proteins/*metabolism ; Cell Line ; Cysteine/*chemistry ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; DNA, Complementary/metabolism ; Dithiothreitol/pharmacology ; Dose-Response Relationship, Drug ; Endoplasmic Reticulum/metabolism ; Evolution, Molecular ; Flow Cytometry ; Gene Deletion ; Glutathione/chemistry ; Humans ; Intracellular Signaling Peptides and Proteins ; Molecular Sequence Data ; Mutation ; Neurodegenerative Diseases/metabolism ; Oxidative Stress ; Oxygen/*chemistry ; Phenotype ; Protein Binding ; Proteins/metabolism ; Recombinant Proteins/chemistry ; Sequence Homology, Amino Acid ; Threonine/chemistry ; Ubiquitin/chemistry ; Valosin Containing Protein ; }, abstract = {Valosin-containing protein (p97/VCP) has been proposed as playing crucial roles in a variety of physiological and pathological processes such as cancer and neurodegeneration. We previously showed that VCP(K524A), an ATPase activity-negative VCP mutant, induced vacuolization, accumulation of ubiquitinated proteins, and cell death, phenotypes commonly observed in neurodegenerative disorders. However, any regulatory mechanism of its ATPase activity has not yet been clarified. Here, we show that oxidative stress readily inactivates VCP ATPase activity. With liquid chromatography/tandem mass spectrometry, we found that at least three cysteine residues were modified by oxidative stress. Of them, the 522nd cysteine (Cys-522) was identified as the site responsible for the oxidative inactivation of VCP. VCP(C522T), a single-amino acid substitution mutant from cysteine to threonine, conferred almost complete resistance to the oxidative inactivation. In response to oxidative stress, VCP strengthened the interaction with Npl4 and Ufd1, both of which are essential in endoplasmic reticulum-associated protein degradation. Cys-522 is located in the second ATP binding motif and is highly conserved in multicellular but not unicellular organisms. Cdc48p (yeast VCP) has threonine in the corresponding amino acid, and it showed resistance to the oxidative inactivation in vitro. Furthermore, a yeast mutant (delta cdc48 + cdc48[T532C]) was shown to be susceptible to oxidants-induced growth inhibition and cell death. These results clearly demonstrate that VCP ATPase activity is regulated by the oxidative modification of the Cys-522 residue. This regulatory mechanism may play a key role in the conversion of oxidative stress to endoplasmic reticulum stress response in multicellular organisms and also in the pathological process of various neurodegenerative disorders.}, } @article {pmid16229974, year = {2006}, author = {Perina, D and Cetkovic, H and Harcet, M and Premzl, M and Lukic-Bilela, L and Müller, WE and Gamulin, V}, title = {The complete set of ribosomal proteins from the marine sponge Suberites domuncula.}, journal = {Gene}, volume = {366}, number = {2}, pages = {275-284}, doi = {10.1016/j.gene.2005.08.015}, pmid = {16229974}, issn = {0378-1119}, mesh = {Animals ; *Evolution, Molecular ; Rats ; Ribosomal Proteins/*genetics ; Ribosomes/*genetics ; Sequence Analysis, Protein ; Sequence Homology, Amino Acid ; Suberites/*genetics ; }, abstract = {The siliceous marine sponge Suberites domuncula is a member of the most ancient and simplest extant phylum of multicellular animals-Porifera, which have branched off first from the common ancestor of all Metazoa. We have determined primary structures of 79 ribosomal proteins (r-proteins) from S. domuncula: 32 proteins from the small ribosomal subunit and 47 proteins from the large ribosomal subunit. Only L39 and L41 polypeptides (51 and 25 residues long in rat, respectively) are missing. The sponge S. domuncula is, after nematode Caenorhabditis elegans and insect Drosophila melanogaster the third representative of invertebrates with known amino acid sequences of all r-proteins. The comparison of S. domuncula r-proteins with r-proteins from D. melanogaster, C. elegans, rat, Arabidopsis thaliana and Saccharomyces cerevisiae revealed very interesting findings. The majority of the sponge r-proteins are more similar to their homologues from rat, than to those either from invertebrates C. elegans and D. melanogaster, or yeast and plant. With few exceptions, the overall sequence conservation between sponge and rat r-proteins is 80% or higher. The phylogenetic tree of concatenated r-proteins from 6 eukaryotic species (rooted with archaeal r-proteins) has the shortest branches connecting sponge and rat. Both model invertebrate organisms experienced recently accelerated evolution and therefore sponge r-proteins very probably better reflect structures of proteins in the ancestral metazoan ribosome, which changed only little during metazoan evolution. Furthermore, r-proteins from the plant A. thaliana are significantly closer to metazoan r-proteins than are those from the yeast S. cerevisiae.}, } @article {pmid16213664, year = {2006}, author = {Kavanau, JL}, title = {Is sleep's 'supreme mystery' unraveling? An evolutionary analysis of sleep encounters no mystery; nor does life's earliest sleep, recently discovered in jellyfish.}, journal = {Medical hypotheses}, volume = {66}, number = {1}, pages = {3-9}, doi = {10.1016/j.mehy.2005.08.036}, pmid = {16213664}, issn = {0306-9877}, mesh = {Animals ; *Biological Evolution ; Cubozoa/*physiology ; Eye/anatomy & histology ; Humans ; Mental Processes/*physiology ; Predatory Behavior/physiology ; Selection, Genetic ; Sleep/*physiology ; Visual Perception/*physiology ; }, abstract = {Biotelemetry has revealed daily 15-h behavioral sleep periods in a cubomedusan jellyfish, Chironex fleckeri. Its sleep is expected to be phylogenetically most primitive, since jellyfish possess only two germ layers. They belong to the phylum Cnidaria, the 'simplest' multicellular organisms with an organized nervous system. Cubomedusae have a complex visual system with 24 eyes of four different types, each type specialized for a different task. Input to these eyes during visually guided fast-swimming predation requires enormous amounts of neural processing, possibly nearly saturating the capacity of their comparatively simple nervous system. These heavy neural demands may account for the need for fifteen hours of sleep. C. fleckeri is the only animal known for which sleep may be either present or absent, dependent on lifestyle. Limited knowledge of behavior of some other cubomedusae suggests that they also possess this faculty. The finding of sleep in C. fleckeri supports current proposals of sleep's origin and basic function. Evolutionary analyses link sleep to a conflict produced by excessive processing demands on multifunctional neural circuitry for detailed focal vision by complex lensed eyes. The conflict arises between the enormous demands of complex visual analysis and needs for split-second control of actions, on the one hand, and non-urgent processing of memories of ongoing and stored events, on the other. Conflict is resolved by deferring the non-urgent processing to periods of sleep. Without sleep, selection would favor the evolution of circuitry 'dedicated' to single or but few tasks, with corresponding lesser efficiency. Had complex lensed eyes of medusae originated as a consequence of selection for increased mating success of males pursuing females, it could have occurred before the evolution of fast-swimming bilateral (three-germ-layered) prey. But if it was a consequence of selection for increased prey-hunting success, the origin of such eyes probably awaited the coexistence of bilateral prey.}, } @article {pmid16212260, year = {2005}, author = {Markov, AV and Kulikov, AM}, title = {[Homologous protein domains in superkingdoms Archaea, Bacteria, and Eukaryota and the problem of the origin of eukaryotes].}, journal = {Izvestiia Akademii nauk. Seriia biologicheskaia}, volume = {}, number = {4}, pages = {389-400}, pmid = {16212260}, issn = {1026-3470}, mesh = {Animals ; Archaea/*genetics/metabolism ; Archaeal Proteins/*genetics/metabolism ; Bacteria/*genetics/metabolism ; Bacterial Proteins/*genetics/metabolism ; Eukaryotic Cells/*physiology ; *Evolution, Molecular ; Mitochondria/genetics/metabolism ; Plastids/genetics/metabolism ; Protein Structure, Tertiary/physiology ; }, abstract = {The distribution of protein domains was analyzed in superkingdoms Archaea, Bacteria, and Eukaryota. About a half of eukaryotic domains have prokaryotic origin. Many domains related to information processing in the nucleocytoplasm were inherited from archaea. Sets of domains associated with metabolism and regulatory and signaling systems were inherited from bacteria. Many signaling and regulatory domains common for bacteria and eukaryotes were responsible for the cellular interaction of bacteria with other components of the microbial community but were involved in coordination of the activity of eukaryotic organelles and cells in multicellular organisms. Many eukaryotic domains of bacterial origin could not originate from ancestral mitochondria and plastids but rather were adopted from other bacteria. An archaeon with the induced incorporation of alien genetic material could be the ancestor of the eukaryotic nucleocytoplasm.}, } @article {pmid16191600, year = {2005}, author = {Nedelcu, AM}, title = {Sex as a response to oxidative stress: stress genes co-opted for sex.}, journal = {Proceedings. Biological sciences}, volume = {272}, number = {1575}, pages = {1935-1940}, pmid = {16191600}, issn = {0962-8452}, mesh = {Algal Proteins/*genetics ; Amino Acid Sequence ; Bayes Theorem ; *Biological Evolution ; Expressed Sequence Tags ; Extracellular Matrix Proteins/*genetics ; Gene Components ; Gene Duplication ; Glycoproteins/*genetics ; Molecular Sequence Data ; Multigene Family/*genetics ; Oxidative Stress/*physiology ; *Phylogeny ; *Sex ; Species Specificity ; Volvox/*genetics/physiology ; }, abstract = {Despite a great deal of interest, the evolutionary origins and roles of sex remain unclear. Recently, we showed that in the multicellular green alga, Volvox carteri, sex is a response to increased levels of reactive oxygen species (ROS), which could be indicative of the ancestral role of sex as an adaptive response to stress-induced ROS. To provide additional support for the suggestion that sex evolved as a response to oxidative stress, this study addresses the hypothesis that genes involved in sexual induction are evolutionarily related to genes associated with various stress responses. In particular, this study investigates the evolutionary history of genes specific to the sexual induction process in V. carteri--including those encoding the sexual inducer (SI) and several SI-induced extracellular matrix (ECM) proteins. Surprisingly, (i) a highly diversified multigene family with similarity to the V. carteri SI and SI-induced pherophorin family is present in its unicellular relative, Chlamydomonas reinhardtii (which lacks both a SI and an ECM) and (ii) at least half of the 12 identified gene members are induced (as inferred from reported expressed sequence tags) under various stress conditions. These findings suggest an evolutionary connection between sex and stress at the gene level, via duplication and/or co-option.}, } @article {pmid16181730, year = {2005}, author = {Takemura, M}, title = {Evolutionary history of the retinoblastoma gene from archaea to eukarya.}, journal = {Bio Systems}, volume = {82}, number = {3}, pages = {266-272}, doi = {10.1016/j.biosystems.2005.08.005}, pmid = {16181730}, issn = {0303-2647}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Cell Cycle ; Cell Differentiation ; Computational Biology/*methods ; *Evolution, Molecular ; *Gene Expression Regulation ; Genes, Archaeal ; Humans ; Methanococcus/genetics ; Models, Biological ; Molecular Sequence Data ; Retinoblastoma Protein/*genetics/*physiology ; Saccharomyces cerevisiae/genetics ; Sequence Homology, Amino Acid ; Species Specificity ; Systems Biology/*methods ; }, abstract = {The retinoblastoma gene product (Rb protein) has a role in progression through the cell cycle, regulating the activities of several transcription factors such as E2F. Since its functional loss results in impaired differentiation in the nervous, hematopoietic, and muscular systems, the Rb protein is very important for cell regulation in multicellular eukaryotes. To gain an insight into the evolutionary history of the Rb gene, I have compared the amino acid sequences of Rb proteins in multicellular eukaryotes and unicellular organisms including yeast, archaeotes, and viruses. Two short amino acid sequences, in the N-terminal and pocket A regions of human Rb protein, found to be well conserved, also in a single protein of Saccharomyces cerevisiae. These sequences were also found in proteins of two archaeotes, Archaeoglobus fulgidus and Methanococcus jannaschii. Further, the most conserved sequence in the pocket B region among multicellular eukaryotic Rb proteins was also conserved in several poxviruses. From these data, I conclude that the pocket A and B regions, backbones of the Rb protein, are derived from different organisms, respectively, the ancestors of archaeote and poxvirus, and that the ancestral pocket B region has been lost during evolutionary history of unicellular eukaryotes.}, } @article {pmid16155929, year = {2006}, author = {Jack, GD and Garst, JF and Cabrera, MC and DeSantis, AM and Slaughter, SM and Jervis, J and Brooks, AI and Potts, M and Helm, RF}, title = {Long term metabolic arrest and recovery of HEK293 spheroids involves NF-kappaB signaling and sustained JNK activation.}, journal = {Journal of cellular physiology}, volume = {206}, number = {2}, pages = {526-536}, doi = {10.1002/jcp.20499}, pmid = {16155929}, issn = {0021-9541}, mesh = {Cell Line ; Desiccation ; Down-Regulation ; Humans ; MAP Kinase Kinase 4/*metabolism/physiology ; Microscopy, Confocal ; NF-kappa B/*metabolism ; Polysaccharides/*pharmacology ; Signal Transduction ; Spheroids, Cellular/cytology/drug effects/*physiology ; Up-Regulation ; }, abstract = {Understanding how cells withstand a depletion of intracellular water is relevant to the study of longevity, aging, and quiescence because one consequence of air-drying is metabolic arrest. After removal of medium, HEK293 spheroids with intracellular water content of approximately 65% survived partial vacuum, with antistatic control, for weeks in the dark at 25 degrees C. In contrast, only a limited exposure of monolayers to air was lethal; the mitochondrion being a target of this stress. The pathways activated during the long-term arrest and recovery of spheroids depended on both NF-kappaB signaling and sustained JNK activation. A cyclical cascade, presumably originating from an intercellular stress signal, led to endogenous cytokine production (TNF-alpha, IL-1b, and IL-8) and propagation of the cellular stress signal through the co-activation of NF-kappaB and JNK. Increased levels of downstream pathway signaling members, specifically Gadd45beta, c-jun, and ATF3 were observed, as was activation of c-jun (phosphorylation). Activation of these pathways permit cells to survive long-term storage and recovery because chemical inhibition of both NF-kappaB nuclear translocation and JNK phosphorylation led to cell death. The capacity of an immortalized cell to enter, and then exit, a state of long-term quiescence, without genetic or chemical intervention, has implications for the study of cell transformation. In addition, the ability to monitor the relevant signaling pathways at endogenous levels, from effector to transcriptional regulator, emphasizes the utility of multicellular aggregate models in delineating stress response pathways.}, } @article {pmid16151249, year = {2005}, author = {Murillo, LA and Newport, G and Lan, CY and Habelitz, S and Dungan, J and Agabian, NM}, title = {Genome-wide transcription profiling of the early phase of biofilm formation by Candida albicans.}, journal = {Eukaryotic cell}, volume = {4}, number = {9}, pages = {1562-1573}, pmid = {16151249}, issn = {1535-9778}, support = {P01 DE007946/DE/NIDCR NIH HHS/United States ; R21 DE015290/DE/NIDCR NIH HHS/United States ; P01 DE07946/DE/NIDCR NIH HHS/United States ; R21 DE15290/DE/NIDCR NIH HHS/United States ; }, mesh = {Antigens, Fungal/genetics/*metabolism ; Biofilms/*growth & development ; Candida albicans/*physiology ; Cell Adhesion ; Gene Expression Profiling ; *Gene Expression Regulation, Fungal ; *Genome ; Hyphae/growth & development ; Oligonucleotide Array Sequence Analysis ; Plankton/genetics/growth & development/metabolism ; RNA, Fungal/genetics/metabolism ; RNA, Messenger/analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {The ability to adhere to surfaces and develop as a multicellular community is an adaptation used by most microorganisms to survive in changing environments. Biofilm formation proceeds through distinct developmental phases and impacts not only medicine but also industry and evolution. In organisms such as the opportunistic pathogen Candida albicans, the ability to grow as biofilms is also an important mechanism for persistence, facilitating its growth on different tissues and a broad range of abiotic surfaces used in medical devices. The early stage of C. albicans biofilm is characterized by the adhesion of single cells to the substratum, followed by the formation of an intricate network of hyphae and the beginning of a dense structure. Changes in the transcriptome begin within 30 min of contact with the substrate and include expression of genes related to sulfur metabolism, in particular MET3, and the equivalent gene homologues of the Ribi regulon in Saccharomyces cerevisiae. Some of these changes are initiated early and maintained throughout the process; others are restricted to the earliest stages of biofilm formation. We identify here a potential alternative pathway for cysteine metabolism and the biofilm-associated expression of genes involved in glutathione production in C. albicans.}, } @article {pmid16118665, year = {2005}, author = {Ren, Q and Paulsen, IT}, title = {Comparative analyses of fundamental differences in membrane transport capabilities in prokaryotes and eukaryotes.}, journal = {PLoS computational biology}, volume = {1}, number = {3}, pages = {e27}, pmid = {16118665}, issn = {1553-734X}, mesh = {Biological Transport ; Computational Biology ; Eukaryotic Cells/classification/*metabolism ; Genome/genetics ; Membrane Transport Proteins/classification/genetics/*metabolism ; Phylogeny ; Prokaryotic Cells/classification/*metabolism ; Substrate Specificity ; }, abstract = {Whole-genome transporter analyses have been conducted on 141 organisms whose complete genome sequences are available. For each organism, the complete set of membrane transport systems was identified with predicted functions, and classified into protein families based on the transporter classification system. Organisms with larger genome sizes generally possessed a relatively greater number of transport systems. In prokaryotes and unicellular eukaryotes, the significant factor in the increase in transporter content with genome size was a greater diversity of transporter types. In contrast, in multicellular eukaryotes, greater number of paralogs in specific transporter families was the more important factor in the increase in transporter content with genome size. Both eukaryotic and prokaryotic intracellular pathogens and endosymbionts exhibited markedly limited transport capabilities. Hierarchical clustering of phylogenetic profiles of transporter families, derived from the presence or absence of a certain transporter family, showed that clustering patterns of organisms were correlated to both their evolutionary history and their overall physiology and lifestyles.}, } @article {pmid16115895, year = {2005}, author = {Liu, Z and Li, H and Derouet, M and Filmus, J and LaCasse, EC and Korneluk, RG and Kerbel, RS and Rosen, KV}, title = {ras Oncogene triggers up-regulation of cIAP2 and XIAP in intestinal epithelial cells: epidermal growth factor receptor-dependent and -independent mechanisms of ras-induced transformation.}, journal = {The Journal of biological chemistry}, volume = {280}, number = {45}, pages = {37383-37392}, doi = {10.1074/jbc.M503724200}, pmid = {16115895}, issn = {0021-9258}, mesh = {Animals ; Anoikis/genetics/physiology ; *Cell Transformation, Neoplastic ; Cells, Cultured ; Down-Regulation ; Epithelial Cells/*metabolism ; ErbB Receptors/*metabolism ; Genes, ras/genetics/*physiology ; Humans ; Inhibitor of Apoptosis Proteins/*genetics/metabolism ; Intestinal Mucosa/cytology ; Transforming Growth Factor alpha/metabolism ; *Up-Regulation ; X-Linked Inhibitor of Apoptosis Protein/*genetics/metabolism ; }, abstract = {Detachment of normal epithelial cells from the extracellular matrix (ECM) triggers apoptosis, a phenomenon called anoikis. Conversely, carcinomas (cancers of epithelial origin) represent three-dimensional disorganized multicellular masses in which cells are deprived of adhesion to the ECM but remain viable. Resistance of cancer cells to anoikis is thought to be critical for tumor progression. However, the knowledge about molecular mechanisms of this type of resistance remains limited. Herein we report that ras oncogene, an established inhibitor of anoikis, triggers a significant upregulation of anti-apoptotic proteins cIAP2 and XIAP in intestinal epithelial cells. We also observed that the effect of ras on cIAP2 requires ras-induced autocrine production of transforming growth factor alpha (TGF-alpha), a ligand for epidermal growth factor receptor, whereas ras-triggered up-regulation of XIAP is TGF-alpha-independent. Moreover, overexpression of either cIAP2 or XIAP in nonmalignant intestinal epithelial cell was found to block anoikis. In addition, an established IAP antagonist Smac or Smac-derived cell-permeable peptide suppressed ras-induced anoikis resistance and subsequent anchorage-independent growth of ras-transformed cells. We conclude that ras-induced overexpression of cIAP2 and XIAP significantly contributes to the ability of ras-transformed intestinal epithelial cells to survive in the absence of adhesion to the ECM and grow in a three-dimensional manner.}, } @article {pmid16111679, year = {2005}, author = {Wienholds, E and Plasterk, RH}, title = {MicroRNA function in animal development.}, journal = {FEBS letters}, volume = {579}, number = {26}, pages = {5911-5922}, doi = {10.1016/j.febslet.2005.07.070}, pmid = {16111679}, issn = {0014-5793}, mesh = {Animals ; Apoptosis ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/physiology ; Cell Differentiation ; Cloning, Molecular ; *Gene Expression Regulation, Developmental ; Genome, Human ; Humans ; Membrane Proteins/metabolism/physiology ; MicroRNAs/*chemistry/metabolism ; Models, Biological ; Neoplasms/metabolism ; Phylogeny ; RNA/*chemistry ; Receptors, Notch/metabolism ; Repressor Proteins/physiology ; Signal Transduction ; Zebrafish ; }, abstract = {MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate gene expression by base-pairing to mRNAs. Hundreds of miRNAs have been identified in various multicellular organisms and many miRNAs are evolutionarily conserved. Although the biological functions of most miRNAs are unknown, miRNAs are predicted to regulate up to 30% of the genes within the human genome. Gradually, we are beginning to understand the functions of individual miRNAs and the general function of miRNA action. Here, we review the recent advances in miRNA biology in animals. Particularly, we focus on the roles of miRNAs in vertebrate development and disease.}, } @article {pmid16099517, year = {2005}, author = {Lal, K and Field, MC and Carlton, JM and Warwicker, J and Hirt, RP}, title = {Identification of a very large Rab GTPase family in the parasitic protozoan Trichomonas vaginalis.}, journal = {Molecular and biochemical parasitology}, volume = {143}, number = {2}, pages = {226-235}, doi = {10.1016/j.molbiopara.2005.06.008}, pmid = {16099517}, issn = {0166-6851}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; DNA, Protozoan/chemistry/genetics ; Dictyostelium/genetics ; Entamoeba histolytica/genetics ; Genes, Protozoan ; Models, Molecular ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Protozoan Proteins/chemistry/*genetics ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Trichomonas vaginalis/classification/*enzymology/genetics ; rab GTP-Binding Proteins/chemistry/*genetics ; }, abstract = {Rab proteins are pivotal components of the membrane trafficking machinery in all eukaryotes. Distinct Rab proteins locate to specific endomembrane compartments and genomic studies suggest that Rab gene diversity correlates with endomembrane system complexity; for example unicellular organisms generally possess 5-20 Rab family members and the size of the repertoire increases to 25-60 in multicellular systems. Here we report 65 open reading frames from the unicellular protozoan Trichomonas vaginalis that encode distinct Rab proteins (TvRabs), indicating a family with complexity that rivals Homo sapiens in number. The detection of gene transcripts for the majority of these genes and conservation of functional motifs strongly suggests that TvRabs retain functionality and likely roles in membrane trafficking. The T. vaginalis Rab family includes orthologues of the conserved subfamilies, Rab1, Rab5, Rab6, Rab7 and Rab11, but the majority of TvRabs are not represented by orthologues in other systems and includes six novel T. vaginalis specific Rab subfamilies (A-F). The extreme size of the T. vaginalis Rab family, the presence of novel subfamilies plus the divergent nature of many TvRab sequences suggest both the presence of a highly complex endomembrane system within Trichomonas and potentially novel Rab functionality. A family of more than 65 Rab genes in a unicellular genome is unexpected, but may be a requirement for progression though an amoeboid life-cycle phase as both Dictyostelium discoideum and Entamoeba histolytica share with T. vaginalis both an amoeboid life cycle stage and very large Rab gene families.}, } @article {pmid16093654, year = {2005}, author = {Brosius, J}, title = {Echoes from the past--are we still in an RNP world?.}, journal = {Cytogenetic and genome research}, volume = {110}, number = {1-4}, pages = {8-24}, doi = {10.1159/000084934}, pmid = {16093654}, issn = {1424-859X}, mesh = {Animals ; *Evolution, Molecular ; *Genome, Human ; Humans ; Retroelements/*genetics ; }, abstract = {Availability of the human genome sequence and those of other species is unmeasured in their value for a comprehensive understanding of the architecture, function and evolution of genomes and cells. Various mechanisms keep genomes in flux and generate intra- and interspecies variation. The conversion of RNA modules into DNA and their more or less random integration into chromosomes (retroposition) is in many lineages including our own the most pervasive and perhaps the most enigmatic. The proclivity of such events in extant multicellular eukaryotes, even in more recent evolutionary times, gives the impression that the transition period from the RNP (ribonucleoprotein) world to the emergence of modern cells, where DNA became the predominant carrier of genetic information, has lasted billions of years and is an endlessly drawn-out process rather than the punctuated event one might expect. Apart from the impact of such RNA-mediated processes as retroposition, the role of RNA in a wide variety of cellular functions has only recently become more widely appreciated.}, } @article {pmid16093567, year = {2005}, author = {Aouacheria, A and Brunet, F and Gouy, M}, title = {Phylogenomics of life-or-death switches in multicellular animals: Bcl-2, BH3-Only, and BNip families of apoptotic regulators.}, journal = {Molecular biology and evolution}, volume = {22}, number = {12}, pages = {2395-2416}, doi = {10.1093/molbev/msi234}, pmid = {16093567}, issn = {0737-4038}, mesh = {Amino Acid Sequence ; Animals ; Apoptosis Regulatory Proteins/*genetics ; Evolution, Molecular ; Membrane Proteins/genetics ; *Phylogeny ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins c-bcl-2/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {In this report, we conducted a comprehensive survey of Bcl-2 family members, a divergent group of proteins that regulate programmed cell death by an evolutionarily conserved mechanism. Using comparative sequence analysis, we found novel sequences in mammals, nonmammalian vertebrates, and in a number of invertebrates. We then asked what conclusions could be drawn from phyletic distribution, intron/exon structures, sequence/structure relationships, and phylogenetic analyses within the updated Bcl-2 family. First, multidomain members having a sequence pattern consistent with the conservation of the Bcl-X(L)/Bax/Bid topology appear to be restricted to multicellular animals and may share a common ancestry. Next, BNip proteins, which were originally identified based on their ability to bind to E1B 19K/Bcl-2 proteins, form three independent monophyletic branches with different evolutionary history. Lastly, a set of Bcl-2 homology 3-only proteins with unrelated secondary structures seems to have evolved after the origin of Metazoa and exhibits diverse expansion after speciation during vertebrate evolution.}, } @article {pmid16093481, year = {2005}, author = {Bishopric, NH}, title = {Evolution of the heart from bacteria to man.}, journal = {Annals of the New York Academy of Sciences}, volume = {1047}, number = {}, pages = {13-29}, doi = {10.1196/annals.1341.002}, pmid = {16093481}, issn = {0077-8923}, support = {R01-HL071094/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Bacteria/metabolism ; Eukaryotic Cells/*physiology ; *Evolution, Molecular ; Heart/growth & development/*physiology ; Homeostasis/physiology ; Humans ; Myocardium/*cytology ; Time ; }, abstract = {This review provides an overview of the evolutionary path to the mammalian heart from the beginnings of life (about four billion years ago) to the present. Essential tools for cellular homeostasis and for extracting and burning energy are still in use and essentially unchanged since the appearance of the eukaryotes. The primitive coelom, characteristic of early multicellular organisms (approximately 800 million years ago), is lined by endoderm and is a passive receptacle for gas exchange, feeding, and sexual reproduction. The cells around this structure express genes homologous to NKX2.5/tinman, and gradual specialization of this "gastroderm" results in the appearance of mesoderm in the phylum Bilateria, which will produce the first primitive cardiac myocytes. Investment of the coelom by these mesodermal cells forms a "gastrovascular" structure. Further evolution of this structure in the bilaterian branches Ecdysoa (Drosophila) and Deuterostoma (amphioxus) culminate in a peristaltic tubular heart, without valves, without blood vessels or blood, but featuring a single layer of contracting mesoderm. The appearance of Chordata and subsequently the vertebrates is accompanied by a rapid structural diversification of this primitive linear heart: looping, unidirectional circulation, an enclosed vasculature, and the conduction system. A later innovation is the parallel circulation to the lungs, followed by the appearance of septa and the four-chambered heart in reptiles, birds, and mammals. With differentiation of the cardiac chambers, regional specialization of the proteins in the cardiac myocyte can be detected in the teleost fish and amphibians. In mammals, growth constraints are placed on the heart, presumably to accommodate the constraints of the body plan and the thoracic cavity, and adult cardiac myocytes lose the ability to re-enter the cell cycle on demand. Mammalian cardiac myocyte innervation betrays the ancient link between the heart, the gut, and reproduction: the vagus nerve controlling heart rate emanates from centers in the central nervous system regulating feeding and affective behavior.}, } @article {pmid16092527, year = {2005}, author = {Lister, R and Hulett, JM and Lithgow, T and Whelan, J}, title = {Protein import into mitochondria: origins and functions today (review).}, journal = {Molecular membrane biology}, volume = {22}, number = {1-2}, pages = {87-100}, doi = {10.1080/09687860500041247}, pmid = {16092527}, issn = {0968-7688}, mesh = {Bacterial Physiological Phenomena ; Bacterial Proteins/metabolism ; *Evolution, Molecular ; Fungal Proteins/metabolism ; Membrane Proteins/physiology ; Membrane Transport Proteins/*physiology ; Mitochondria/*metabolism ; Mitochondrial Proteins/*metabolism ; Protein Transport ; Yeasts/physiology ; }, abstract = {Mitochondria are organelles derived from alpha-proteobacteria over the course of one to two billion years. Mitochondria from the major eukaryotic lineages display some variation in functions and coding capacity but sequence analysis demonstrates them to be derived from a single common ancestral endosymbiont. The loss of assorted functions, the transfer of genes to the nucleus, and the acquisition of various 'eukaryotic' proteins have resulted in an organelle that contains approximately 1000 different proteins, with most of these proteins imported into the organelle across one or two membranes. A single translocase in the outer membrane and two translocases in the inner membrane mediate protein import. Comparative sequence analysis and functional complementation experiments suggest some components of the import pathways to be directly derived from the eubacterial endosymbiont's own proteins, and some to have arisen 'de novo' at the earliest stages of 'mitochondrification' of the endosymbiont. A third class of components appears lineage-specific, suggesting they were incorporated into the process of protein import long after mitochondria was established as an organelle and after the divergence of the various eukaryotic lineages. Protein sorting pathways inherited from the endosymbiont have been co-opted and play roles in intraorganelle protein sorting after import. The import apparatus of animals and fungi show significant similarity to one another, but vary considerably to the plant apparatus. Increasing complexity in the eukaryotic lineage, i.e., from single celled to multi-cellular life forms, has been accompanied by an expansion in genes encoding each component, resulting in small gene families encoding many components. The functional differences in these gene families remain to be elucidated, but point to a mosaic import apparatus that can be regulated by a variety of signals.}, } @article {pmid16086850, year = {2005}, author = {Wilkins, A and Szafranski, K and Fraser, DJ and Bakthavatsalam, D and Müller, R and Fisher, PR and Glöckner, G and Eichinger, L and Noegel, AA and Insall, RH}, title = {The Dictyostelium genome encodes numerous RasGEFs with multiple biological roles.}, journal = {Genome biology}, volume = {6}, number = {8}, pages = {R68}, pmid = {16086850}, issn = {1474-760X}, mesh = {Actins/genetics ; Animals ; Dictyostelium/cytology/*genetics ; Gene Expression Regulation, Developmental ; Genes, Protozoan/*genetics ; Genome, Protozoan/*genetics ; Germ-Free Life ; Movement ; Mutation/genetics ; Phenotype ; Phylogeny ; Protein Binding ; Protein Structure, Tertiary ; Sequence Analysis, DNA ; ras Guanine Nucleotide Exchange Factors/chemistry/*genetics/*metabolism ; rho GTP-Binding Proteins/metabolism ; }, abstract = {BACKGROUND: Dictyostelium discoideum is a eukaryote with a simple lifestyle and a relatively small genome whose sequence has been fully determined. It is widely used for studies on cell signaling, movement and multicellular development. Ras guanine-nucleotide exchange factors (RasGEFs) are the proteins that activate Ras and thus lie near the top of many signaling pathways. They are particularly important for signaling in development and chemotaxis in many organisms, including Dictyostelium.

RESULTS: We have searched the genome for sequences encoding RasGEFs. Despite its relative simplicity, we find that the Dictyostelium genome encodes at least 25 RasGEFs, with a few other genes encoding only parts of the RasGEF consensus domains. All appear to be expressed at some point in development. The 25 genes include a wide variety of domain structures, most of which have not been seen in other organisms. The LisH domain, which is associated with microtubule binding, is seen particularly frequently; other domains that confer interactions with the cytoskeleton are also common. Disruption of a sample of the novel genes reveals that many have clear phenotypes, including altered morphology and defects in chemotaxis, slug phototaxis and thermotaxis.

CONCLUSION: These results suggest that the unexpectedly large number of RasGEF genes reflects an evolutionary expansion of the range of Ras signaling rather than functional redundancy or the presence of multiple pseudogenes.}, } @article {pmid16084025, year = {2005}, author = {Bubanovic, I and Najman, S and Andjelkovic, Z}, title = {Origin and evolution of viruses: escaped DNA/RNA sequences as evolutionary accelerators and natural biological weapons.}, journal = {Medical hypotheses}, volume = {65}, number = {5}, pages = {868-872}, doi = {10.1016/j.mehy.2005.05.038}, pmid = {16084025}, issn = {0306-9877}, mesh = {Animals ; Base Sequence ; Biological Evolution ; Biological Warfare ; DNA, Viral/*genetics ; Evolution, Molecular ; Humans ; *Models, Genetic ; Molecular Sequence Data ; Mutation/genetics ; *Origin of Life ; RNA, Viral/*genetics ; *Selection, Genetic ; Virus Diseases/*genetics ; Viruses/*genetics ; }, abstract = {Knowledge of the origin and evolution of viruses could provide a better understanding of a number of phenomena in the field of evolution such as the origin and development of multi-cellular organisms, the rapid diversification of species over the last 600-700 million years and the lack of transitional forms in the evolution of species ("missing links") etc. One of the possible effects of escaped DNA/RNA sequences or viruses on the evolution of multi-cellular organisms, especially vertebrates, could be the phenomenon of horizontal transmission and dissemination of genes. Interestingly, if so, this effect could be considered as a model of primeval and natural genetic engineering. Other possible links between the evolution of multi-cellular organisms and viruses are connected with the fact that viruses represent the source of different forms of selective pressure such as epidemics of infectious diseases, autoimmunity, malignant alteration, reproductive efficiency, etc. At the same time, these two models of "long-term evolutionary relations" could represent "key factors" in the evolution between viruses and multi-cellular organisms. The capability of a genome to produce and emit DNA/RNA sequences or de novo created viruses which can be a vector of genes horizontal transmission and/or cause selective pressure on concurrent or predator species gives a new characteristic to viruses--the possibility of their acting as natural biological weapons. Finally, possibly evolutionary advantages of this genome capability could be one of explanations for the phenomena such as genome instability and its ability to emit DNA/RNA sequences and/or de novo created viruses, as well as evolutionary conservation of this unique phenomena.}, } @article {pmid16076249, year = {2005}, author = {Mangeat, B and Trono, D}, title = {Lentiviral vectors and antiretroviral intrinsic immunity.}, journal = {Human gene therapy}, volume = {16}, number = {8}, pages = {913-920}, doi = {10.1089/hum.2005.16.913}, pmid = {16076249}, issn = {1043-0342}, mesh = {APOBEC-3G Deaminase ; Adaptation, Physiological ; Biological Evolution ; Cytidine Deaminase/metabolism ; Genetic Therapy/*trends ; Genetic Vectors ; Hepatitis B, Chronic/genetics/therapy ; Humans ; *Immunity, Innate ; Lentivirus/*genetics ; Neoplasms/genetics/therapy ; Nucleoside Deaminases ; Proteins/*genetics/*immunology ; Repressor Proteins ; *Retroelements ; Transduction, Genetic ; Viruses/pathogenicity ; }, abstract = {Multicellular organisms have evolved under relentless attacks from pathogens, and as a consequence have spiked their genomes with numerous genes that serve to thwart these threats, notably through the building of the innate and adaptive arms of the immune system. The innate immune system is by far the most ancient, being found as widely as in plants and Drosophila, while adaptive immunity arose with the emergence of cartilaginous fishes. Innate immunity enters rapidly into the game during the course of an infection and generally involves the recognition by specific cellular receptors of common pathogen-associated patterns to elicit broad defensive responses, mediated in humans by interferons, macrophages, and natural killer cells, amongst others. When innate immunity fails to eradicate the infection quickly, adaptive immune responses enter into play, to generate exquisitely specific defenses to virtually any pathogen, thanks to a quasi-infinite repertoire of nonself receptors and effectors. A specific form of innate immunity, coined "intrinsic immunity," completes this protection by providing a constant, always-on, line of defense, generally through intracellular obstacles to the replication of pathogens. This component of the immune system has gained much attention as it was discovered that it is a cornerstone of the resistance of mammals against retroviruses. One of these newly discovered intracellular molecular weapons, the APOBEC family of proteins, is active against several classes of retroelements. We present here the current state of knowledge on this rapidly evolving field and discuss implications for gene therapy.}, } @article {pmid16049098, year = {2005}, author = {Nelson, CM and Jean, RP and Tan, JL and Liu, WF and Sniadecki, NJ and Spector, AA and Chen, CS}, title = {Emergent patterns of growth controlled by multicellular form and mechanics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {102}, number = {33}, pages = {11594-11599}, pmid = {16049098}, issn = {0027-8424}, mesh = {Animals ; Cattle ; Cell Proliferation ; Cells, Cultured ; Cytoskeleton/metabolism ; Endothelial Cells/*cytology/physiology ; Epithelial Cells/*cytology ; Morphogenesis ; Rats ; Stress, Mechanical ; }, abstract = {Spatial patterns of cellular growth generate mechanical stresses that help to push, fold, expand, and deform tissues into their specific forms. Genetic factors are thought to specify patterns of growth and other behaviors to drive morphogenesis. Here, we show that tissue form itself can feed back to regulate patterns of proliferation. Using micro-fabrication to control the organization of sheets of cells, we demonstrated the emergence of stable patterns of proliferative foci. Regions of concentrated growth corresponded to regions of high tractional stress generated within the sheet, as predicted by a finite-element model of multicellular mechanics and measured directly by using a micromechanical force sensor array. Inhibiting actomyosin-based tension or cadherin-mediated connections between cells disrupted the spatial pattern of proliferation. These findings demonstrate the existence of patterns of mechanical forces that originate from the contraction of cells, emerge from their multicellular organization, and result in patterns of growth. Thus, tissue form is not only a consequence but also an active regulator of tissue growth.}, } @article {pmid16044354, year = {2005}, author = {Awata, H and Noto, T and Endoh, H}, title = {Differentiation of somatic mitochondria and the structural changes in mtDNA during development of the dicyemid Dicyema japonicum (Mesozoa).}, journal = {Molecular genetics and genomics : MGG}, volume = {273}, number = {6}, pages = {441-449}, pmid = {16044354}, issn = {1617-4615}, mesh = {Animals ; DNA Replication ; DNA, Circular/chemistry/metabolism ; DNA, Mitochondrial/analysis/*biosynthesis/*chemistry ; Mitochondria/chemistry/*genetics ; Nucleic Acid Conformation ; Parasites/*embryology/*genetics ; Replication Origin ; }, abstract = {Dicyemids (Mesozoa) are extremely simple multicellular parasites found in the kidneys of cephalopods. Their mitochondria are known to contain single-gene minicircle DNAs. However, it is not known if the minicircles represent the sole form of mitochondrial genome in these organisms. Here we demonstrate that high-molecular-weight (HMW) mtDNA is present in dicyemids. This form of mtDNA is probably limited to germ cells, and has been analyzed by PCR and Southern hybridization. In situ hybridization revealed that mtDNA is initially amplified during early embryogenesis, and then gradually decreases in copy number as larval development proceeds. Furthermore, we demonstrated using BrdU as a tracer that many of the mitochondria in terminally differentiated somatic cells no longer support DNA synthesis. Taking these observations into account, we propose an "amplification-dilution" model for mesozoan mtDNA. "Stem" mitochondria in the germ cells (1) amplify the HMW form of mtDNA in early embryos, followed by minicircle formation via DNA rearrangement, or (2) selectively replicate minicircles from the HMW DNA, concomitantly with the differentiation of the soma. Minicircle formation may itself lead to the loss of replication origins. Thereafter, the minicircles are simply distributed to daughter mitochondria without replication, resulting in the "somatic" mitochondria, which have lost the replicative form of the HMW mtDNA. The change in mtDNA configuration is discussed in relation to mitochondrial differentiation.}, } @article {pmid16044249, year = {2005}, author = {Stenøien, HK and Stephan, W}, title = {Global mRNA stability is not associated with levels of gene expression in Drosophila melanogaster but shows a negative correlation with codon bias.}, journal = {Journal of molecular evolution}, volume = {61}, number = {3}, pages = {306-314}, pmid = {16044249}, issn = {0022-2844}, mesh = {Animals ; Bias ; Codon/*genetics ; Drosophila melanogaster/*genetics ; Gene Expression Regulation/*genetics ; RNA Stability/*genetics ; Thermodynamics ; }, abstract = {A multitude of factors contribute to the regulation of gene expression in living cells. The relationship between codon usage bias and gene expression has been extensively studied, and it has been shown that codon bias may have adaptive significance in many unicellular and multicellular organisms. Given the central role of mRNA in post-transcriptional regulation, we hypothesize that mRNA stability is another important factor associated either with positive or negative regulation of gene expression. We have conducted genome-wide studies of the association between gene expression (measured as transcript abundance in public EST databases), mRNA stability, codon bias, GC content, and gene length in Drosophila melanogaster. To remove potential bias of gene length inherently present in EST libraries, gene expression is measured as normalized transcript abundance. It is demonstrated that codon bias and GC content in second codon position are positively associated with transcript abundance. Gene length is negatively associated with transcript abundance. The stability of thermodynamically predicted mRNA secondary structures is not associated with transcript abundance, but there is a negative correlation between mRNA stability and codon bias. This finding does not support the hypothesis that codon bias has evolved as an indirect consequence of selection favoring thermodynamically stable mRNA molecules.}, } @article {pmid16029466, year = {2005}, author = {Behar, A and Yuval, B and Jurkevitch, E}, title = {Enterobacteria-mediated nitrogen fixation in natural populations of the fruit fly Ceratitis capitata.}, journal = {Molecular ecology}, volume = {14}, number = {9}, pages = {2637-2643}, doi = {10.1111/j.1365-294X.2005.02615.x}, pmid = {16029466}, issn = {0962-1083}, mesh = {Animals ; Base Sequence ; Ceratitis capitata/*metabolism/*microbiology ; DNA Primers ; Dinitrogenase Reductase/metabolism ; Enterobacteriaceae/*genetics/metabolism ; Gastrointestinal Tract/metabolism/microbiology ; Likelihood Functions ; Models, Genetic ; Molecular Sequence Data ; Nitrogen/*metabolism ; Oxidoreductases/genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {Nitrogen, although abundant in the atmosphere, is paradoxically a limited resource for multicellular organisms. In the Animalia, biological nitrogen fixation has solely been demonstrated in termites. We found that all individuals of field-collected Mediterranean fruit flies (Ceratitis capitata) harbour large diazotrophic enterobacterial populations that express dinitrogen reductase in the gut. Moreover, nitrogen fixation was demonstrated in isolated guts and in live flies and may significantly contribute to the fly's nitrogen intake. The presence of similar bacterial consortia in additional insect orders suggests that nitrogen fixation occurs in vast pools of terrestrial insects. On such a large scale, this phenomenon may have a considerable impact on the nitrogen cycle.}, } @article {pmid16011468, year = {2005}, author = {McEligot, AJ and Yang, S and Meyskens, FL}, title = {Redox regulation by intrinsic species and extrinsic nutrients in normal and cancer cells.}, journal = {Annual review of nutrition}, volume = {25}, number = {}, pages = {261-295}, doi = {10.1146/annurev.nutr.25.050304.092633}, pmid = {16011468}, issn = {0199-9885}, support = {CA62203/CA/NCI NIH HHS/United States ; }, mesh = {*Antioxidants ; Ascorbic Acid ; Carotenoids ; Diet ; Glutathione/metabolism ; Homeostasis ; Humans ; Mitochondria/metabolism ; *Neoplasms ; *Nutritional Physiological Phenomena ; Oxidation-Reduction ; *Oxidative Stress ; Selenium ; Signal Transduction ; Tumor Cells, Cultured ; }, abstract = {Cells in multicellular organisms are exposed to both endogenous oxidative stresses generated metabolically and to oxidative stresses that originate from neighboring cells and from other tissues. To protect themselves from oxidative stress, cells are equipped with reducing buffer systems (glutathione/GSH and thioredoxin/thioredoxin reductase) and have developed several enzymatic mechanisms against oxidants that include catalase, superoxide dismutase, and glutathione peroxidase. Other major extrinsic defenses (from the diet) include ascorbic acid, beta-carotene and other carotenoids, and selenium. Recent evidence indicates that in addition to their antioxidant function, several of these redox species and systems are involved in regulation of biological processes, including cellular signaling, transcription factor activity, and apoptosis in normal and cancer cells. The survival and overall well-being of the cell is dependent upon the balance between the activity and the intracellular levels of these antioxidants as well as their interaction with various regulatory factors, including Ref-1, nuclear factor-kappaB, and activating protein-1.}, } @article {pmid16005503, year = {2005}, author = {Yoshida, H and Yokomori, T and Suyama, A}, title = {A simple classification of the volvocine algae by formal languages.}, journal = {Bulletin of mathematical biology}, volume = {67}, number = {6}, pages = {1339-1354}, doi = {10.1016/j.bulm.2005.03.001}, pmid = {16005503}, issn = {0092-8240}, mesh = {Animals ; Biological Evolution ; Language ; Models, Biological ; *Models, Theoretical ; Volvox/*classification/ultrastructure ; }, abstract = {There are several explanations of why certain primitive multicellular organisms aggregate in particular forms and why their constituent cells cooperate with one another to a particular degree. Utilizing the framework of formal language theory, we have derived one possible simple classification of the volvocine algae-one of the primitive multicells-for some forms of aggregation and some degrees of cooperation among cells. The volvocine algae range from the unicellular Chlamydomonas to the multicellular Volvox globator, which has thousands of cells. The classification we use in this paper is based on the complexity of Parikh sets of families on Chomsky hierarchy in formal language theory. We show that an alga with almost no space closed to the environment, e.g., Gonium pectorale, can be characterized by PsFIN, one with a closed space and no cooperation, e.g., Eudorina elegans, by PsCF, and one with a closed space and cooperation, e.g., Volvox globator, by PslambdauSC. This classification should provide new insights into the necessity for specific forms and degrees of cooperation in the volvocine algae.}, } @article {pmid15990118, year = {2006}, author = {Finkel, RW}, title = {Model for energy oscillations in cells.}, journal = {Journal of theoretical biology}, volume = {238}, number = {2}, pages = {286-289}, doi = {10.1016/j.jtbi.2005.05.002}, pmid = {15990118}, issn = {0022-5193}, mesh = {Animals ; Cell Size ; Cells/*metabolism ; Cytoplasm/*metabolism ; *Energy Metabolism ; Models, Biological ; Periodicity ; Saccharomyces cerevisiae/cytology/metabolism ; }, abstract = {Rapid periodic pulses have been observed in yeast cell walls and these pulsations must be accompanied by coherent oscillations of energy. Such energy oscillations are likely to be a common feature in cells and we explore other consequences, either known or unknown, that may originate from chemical oscillations of small amplitude. We do not consider specific mechanisms for the energy oscillations, but here we accept their existence as a fact following from the yeast experiments. Chemical oscillators are treated as generic quantum oscillators and this model predicts that observed frequencies should have a simple volume-dependence where smaller cells exhibit higher frequencies than their larger counterparts. An extension to multicellular organisms then affords a derivation of the celebrated Kleiber law that evaluates both the numerical coefficient and the 34 exponent of mass. Calculations of activation energies and efficiencies at experimental temperatures follow. Finally, the model is applied to derive established expressions for blood flow and pulse rate. We conclude that the model reflects some common metabolic process insofar as it agrees with diverse quantitative findings while using minimal input data and without introducing free parameters.}, } @article {pmid15986453, year = {2005}, author = {Dunn, CW}, title = {Complex colony-level organization of the deep-sea siphonophore Bargmannia elongata (Cnidaria, Hydrozoa) is directionally asymmetric and arises by the subdivision of pro-buds.}, journal = {Developmental dynamics : an official publication of the American Association of Anatomists}, volume = {234}, number = {4}, pages = {835-845}, doi = {10.1002/dvdy.20483}, pmid = {15986453}, issn = {1058-8388}, mesh = {Animal Structures/growth & development/*ultrastructure ; Animals ; Body Patterning/*physiology ; Hydrozoa/*anatomy & histology/*growth & development ; Microscopy, Electron, Scanning ; Oceans and Seas ; Phylogeny ; }, abstract = {Siphonophores are free-swimming colonial hydrozoans (Cnidaria) composed of asexually produced multicellular zooids. These zooids, which are homologous to solitary animals, are functionally specialized and arranged in complex species-specific patterns. The coloniality of siphonophores provides an opportunity to study the major transitions in evolution that give rise to new levels of biological organization, but siphonophores are poorly known because they are fragile and live in the open ocean. The organization and development of the deep-sea siphonophore Bargmannia elongata is described here using specimens collected with a remotely operated underwater vehicle. Each bud gives rise to a precise, directionally asymmetric sequence of zooids through a stereotypical series of subdivisions, rather than to a single zooid as in most other hydrozoans. This initial description of development in a deep-sea siphonophore provides an example of how precise colony-level organization can arise, and illustrates that the morphological complexity of cnidarians is greater than is often assumed.}, } @article {pmid15978523, year = {2005}, author = {Dumitriu, IE and Baruah, P and Manfredi, AA and Bianchi, ME and Rovere-Querini, P}, title = {HMGB1: guiding immunity from within.}, journal = {Trends in immunology}, volume = {26}, number = {7}, pages = {381-387}, doi = {10.1016/j.it.2005.04.009}, pmid = {15978523}, issn = {1471-4906}, mesh = {Animals ; Cell Differentiation ; Cell Nucleus/immunology ; Dendritic Cells/cytology/immunology ; Extracellular Space/immunology ; HMGB1 Protein/*immunology/metabolism ; Humans ; Immunity, Innate ; Inflammation/immunology/therapy ; Models, Immunological ; }, abstract = {Two of the main challenges that eukaryotic multicellular organisms faced during evolution were to eliminate and replace dying cells and to cope with invading microorganisms. The innate immune system evolved to handle both tasks: to scavenge cellular debris and to form the first line of defence against microbes. In this review, we focus on high mobility group box 1 (HMGB1) protein as a common signal that alerts the innate immune system to excessive or deregulated cell death and to microbial invasion. HMGB1, which is well known nuclear protein, has revealed unexpected facets as an extracellular mediator. The role of HMGB1 as an endogenous molecule that facilitates immune responses and has an important role in tissue homeostasis and disease will be highlighted here.}, } @article {pmid15976489, year = {2005}, author = {Hornef, MW and Normark, S and Henriques-Normark, B and Rhen, M}, title = {Bacterial evasion of innate defense at epithelial linings.}, journal = {Chemical immunology and allergy}, volume = {86}, number = {}, pages = {72-98}, doi = {10.1159/000086652}, pmid = {15976489}, issn = {1660-2242}, mesh = {Animals ; Antimicrobial Cationic Peptides/metabolism ; Bacteria/*immunology/*pathogenicity ; Bacterial Adhesion ; Epithelium/immunology/microbiology ; Humans ; Hydrogen-Ion Concentration ; *Immunity, Innate ; Models, Biological ; Opsonin Proteins/metabolism ; Peptide Hydrolases/metabolism ; }, abstract = {The evolution of multicellular organisms has been, and continues to be, paralleled by the evolution of the surrounding microbial flora. This intimate coexistence between higher host organisms and microbes has generated a myriad of adaptation strategies at both sides to cope with, or even benefit from the given conditions. On the host side, the development of an effective immune defence system allowed the maintenance of an astonishingly stable homeostasis on many body sites, and even the establishment of sterile surfaces at vulnerable anatomical sites. On the other hand, microbial diversity has led to the establishment of a large number of microbial life styles that allow persistence and proliferation in the presence of host defense mechanisms. The following review describes bacterial strategies to circumvent or modify host defenses that operate at the epithelial lining. It illustrates the enormous diversity of mechanisms that are part of the complex interplay between microbial organisms and the host. It also reflects the dramatic progress made in the understanding of the mammalian immune defense system which many times has been initiated by the surprising results from the study of microbial pathogenesis.}, } @article {pmid15975432, year = {2005}, author = {Williams, JG and Noegel, AA and Eichinger, L}, title = {Manifestations of multicellularity: Dictyostelium reports in.}, journal = {Trends in genetics : TIG}, volume = {21}, number = {7}, pages = {392-398}, doi = {10.1016/j.tig.2005.05.002}, pmid = {15975432}, issn = {0168-9525}, mesh = {Animals ; Chemotaxis ; Chromosome Mapping ; Computational Biology ; Cytoskeleton/metabolism ; Dictyostelium/*genetics/*physiology ; Drosophila ; Evolution, Molecular ; *Genome ; Genome, Fungal ; Models, Biological ; Models, Genetic ; Phylogeny ; Protein Structure, Tertiary ; Signal Transduction ; }, abstract = {The recent release of the Dictyostelium genome sequence is important because Dictyostelium has become a much-favoured model system for cell and developmental biologists. The sequence has revealed a remarkably high total number of approximately 12 500 genes, only a thousand fewer than are encoded by Drosophila. Previous protein-sequence comparisons suggested that Dictyostelium is evolutionarily closer to animals and fungi than to plants, and the global protein sequence comparison, now made possible by the genome sequence, confirms this. This review focuses on several classes of proteins that are shared by Dictyostelium and animals: a highly sophisticated array of microfilament components, a large family of G-protein-coupled receptors and a diverse set of SH2 domain-containing proteins. The presence of these proteins strengthens the case for a relatively close relationship with animals and extends the range of problems that can be addressed using Dictyostelium as a model organism.}, } @article {pmid15963254, year = {2005}, author = {Twomey, C and McCarthy, JV}, title = {Pathways of apoptosis and importance in development.}, journal = {Journal of cellular and molecular medicine}, volume = {9}, number = {2}, pages = {345-359}, pmid = {15963254}, issn = {1582-1838}, mesh = {Animals ; Apoptosis/genetics/*physiology ; Caenorhabditis elegans/embryology/genetics/physiology ; Caspases/genetics/metabolism ; Drosophila melanogaster/embryology/genetics/physiology ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Mice ; Models, Biological ; Mutation ; Signal Transduction/genetics/*physiology ; }, abstract = {The elimination of cells by programmed cell death is a fundamental event in development where multicellular organisms regulate cell numbers or eliminate cells that are functionally redundant or potentially detrimental to the organism. The evolutionary conservation of the biochemical and genetic regulation of programmed cell death across species has allowed the genetic pathways of programmed cell death determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster to act as models to delineate the genetics and regulation of cell death in mammalian cells. These studies have identified cell autonomous and non-autonomous mechanisms that regulate of cell death and reveal that developmental cell death can either be a pre-determined cell fate or the consequence of insufficient cell interactions that normally promote cell survival.}, } @article {pmid15962724, year = {2005}, author = {Schuiling, GA}, title = {Reproduce and die! Why aging? Part I.}, journal = {Journal of psychosomatic obstetrics and gynaecology}, volume = {26}, number = {1}, pages = {73-77}, doi = {10.1080/01674820500065010}, pmid = {15962724}, issn = {0167-482X}, mesh = {Aging/*physiology ; Biological Evolution ; *Death ; Humans ; Reproductive Behavior/*physiology ; }, abstract = {In multi-cellular organisms--and hence also in man--aging and dying is the fate of the soma, i.e., the body proper; germ cells are--at least in principle--immortal. As the soma can be considered to be the "service compartment" of the germ cells, it loses its function once a species' phase of reproduction is over. Hence, there is an intimate relationship between reproduction and aging, and therefore also between a species' reproductive strategy and aging: there has been no selection for maintenance of the soma beyond the reproductive phase of life (when there is no reproduction, there is also no natural selection). As a consequence, mechanisms, important for maintenance of the soma during the reproductive phase, increasingly begin to fail once this phase is over, resulting in an accumulation of all kinds of pathology and genetic errors, rendering an individual increasingly more prone to a variety of (internal and external) attacks. In the end, the soma collapses, be it due to organ failure, a neoplasm or to a final external push, e.g., an infection.}, } @article {pmid15940278, year = {2005}, author = {Tata, JR}, title = {One hundred years of hormones.}, journal = {EMBO reports}, volume = {6}, number = {6}, pages = {490-496}, pmid = {15940278}, issn = {1469-221X}, mesh = {*Biological Evolution ; Endocrinology/*history ; History, 20th Century ; History, 21st Century ; Hormones/*metabolism/*physiology ; Models, Biological ; Signal Transduction/*physiology ; }, abstract = {A new name sparked multidisciplinary research in endocrinology, which shed light on chemical communication in multicellular organisms}, } @article {pmid15936118, year = {2005}, author = {Morel, O and Morel, N and Hugel, B and Jesel, L and Vinzio, S and Goichot, B and Bakouboula, B and Grunebaum, L and Freyssinet, JM and Toti, F}, title = {[The significance of circulating microparticles in physiology, inflammatory and thrombotic diseases].}, journal = {La Revue de medecine interne}, volume = {26}, number = {10}, pages = {791-801}, doi = {10.1016/j.revmed.2005.03.015}, pmid = {15936118}, issn = {0248-8663}, mesh = {Adult ; Apoptosis/*physiology ; *Biomarkers ; Cell Communication/physiology ; Cell Membrane/physiology ; Cytoskeleton/physiology ; Female ; Hemostasis ; Homeostasis ; Humans ; Immunity/physiology ; Inflammation/*physiopathology ; Male ; Microbodies/physiology ; Particle Size ; Phagocytosis ; Phenotype ; Pregnancy ; Selectins/physiology ; Thromboplastin/*physiology ; Thrombosis/*physiopathology ; }, abstract = {BACKGROUND: In multicellular organisms, apoptosis and subsequent microparticle shedding play a key role in homeostasis. Having long been considered as << cellular dust >>, microparticles released in biological fluids upon cell activation or apoptosis appear as multifunctional bioeffectors involved in the modulation of key functions including immunity, inflammation, hemostasis and thrombosis, angiogenesis. MP constitute reliable markers of vascular damage, accessible to biological detection whilst the cells they originate from remain sequestered in tissues or are promptly submitted to phagocytosis.

RECENT FINDINGS: MP modulate biological functions of target cells through the transfer of cytoplasmic content, lipids and membrane receptors. The pharmacological modulation of circulating levels of microparticles could be of particular interest in thrombotic or inflammatory diseases, cancer or hemophilia.

CONCLUSION: MP can now be viewed not only as a hallmark of cell damage but also as a true biological tool.}, } @article {pmid15935676, year = {2005}, author = {Matz, C and Kjelleberg, S}, title = {Off the hook--how bacteria survive protozoan grazing.}, journal = {Trends in microbiology}, volume = {13}, number = {7}, pages = {302-307}, doi = {10.1016/j.tim.2005.05.009}, pmid = {15935676}, issn = {0966-842X}, mesh = {*Adaptation, Biological ; Animals ; *Bacterial Physiological Phenomena ; Biological Evolution ; Ecology ; Eukaryota/microbiology/*physiology ; Food Chain ; }, abstract = {Bacterial growth and survival in numerous environments are constrained by the action of bacteria-consuming protozoa. Recent findings suggest that bacterial adaptations against protozoan predation might have a significant role in bacterial persistence and diversification. We argue that selective predation has given rise to diverse routes of bacterial defense, including adaptive mechanisms in bacterial biofilms, and has promoted major transitions in bacterial evolution, such as multicellularity and pathogenesis. We propose that studying predation-driven adaptations will provide an exciting frontier for microbial ecology and evolution at the interface of prokaryotes and eukaryotes.}, } @article {pmid15933773, year = {2005}, author = {Wanderley, JL and Benjamin, A and Real, F and Bonomo, A and Moreira, ME and Barcinski, MA}, title = {Apoptotic mimicry: an altruistic behavior in host/Leishmania interplay.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {38}, number = {6}, pages = {807-812}, doi = {10.1590/s0100-879x2005000600001}, pmid = {15933773}, issn = {0100-879X}, mesh = {Animals ; Apoptosis/immunology/*physiology ; Arginase/metabolism ; Host-Parasite Interactions/immunology/physiology ; Immune System/physiology ; Leishmania/immunology/*physiology ; Macrophages/physiology ; Phosphatidylserines/immunology/*physiology ; }, abstract = {Apoptosis is the most common phenotype observed when cells die through programmed cell death. The morphologic and biochemical changes that characterize apoptotic cells depend on the activation of a diverse set of genes. Apoptosis is essential for multicellular organisms since their development and homeostasis are dependent on extensive cell renewal. In fact, there is strong evidence for the correlation between the emergence of multicellular organisms and apoptosis during evolution. On the other hand, no obvious advantages can be envisaged for unicellular organisms to carry the complex machinery required for programmed cell death. However, accumulating evidence shows that free-living and parasitic protozoa as well as yeasts display apoptotic markers. This phenomenon has been related to altruistic behavior, when a subpopulation of protozoa or yeasts dies by apoptosis, with clear benefits for the entire population. Recently, phosphatidylserine (PS) exposure and its recognition by a specific receptor (PSR) were implicated in the infectivity of amastigote forms of Leishmania, an obligatory vertebrate intramacrophagic parasite, showing for the first time that unicellular organisms use apoptotic features for the establishment and/or maintenance of infection. Here we focus on PS exposure in the outer leaflet of the plasma membrane--an early hallmark of apoptosis--and how it modulates the inflammatory activity of phagocytic cells. We also discuss the possible mechanisms by which PS exposure can define Leishmania survival inside host cells and the evolutionary implications of apoptosis at the unicellular level.}, } @article {pmid15925584, year = {2005}, author = {Sánchez Alvarado, A and Kang, H}, title = {Multicellularity, stem cells, and the neoblasts of the planarian Schmidtea mediterranea.}, journal = {Experimental cell research}, volume = {306}, number = {2}, pages = {299-308}, doi = {10.1016/j.yexcr.2005.03.020}, pmid = {15925584}, issn = {0014-4827}, support = {R01 GM57260/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Germ Cells/*physiology ; Humans ; Models, Biological ; Phylogeny ; Planarians/*physiology ; Pluripotent Stem Cells/*physiology ; Regeneration/*physiology ; }, abstract = {All multicellular organisms depend on stem cells for their survival and perpetuation. Their central role in reproductive, embryonic, and post-embryonic processes, combined with their wide phylogenetic distribution in both the plant and animal kingdoms intimates that the emergence of stem cells may have been a prerequisite in the evolution of multicellular organisms. We present an evolutionary perspective on stem cells and extend this view to ascertain the value of current comparative studies on various invertebrate and vertebrate somatic and germ line stem cells. We suggest that somatic stem cells may be ancestral, with germ line stem cells being derived later in the evolution of multicellular organisms. We also propose that current studies of stem cell biology are likely to benefit from studying the somatic stem cells of simple metazoans. Here, we present the merits of neoblasts, a largely unexplored, yet experimentally accessible population of stem cells found in the planarian Schmidtea mediterranea. We introduce what we know about the neoblasts, and posit some of the questions that will need to be addressed in order to better resolve the relationship between planarian somatic stem cells and those found in other organisms, including humans.}, } @article {pmid15903456, year = {2005}, author = {Lappa, M}, title = {Discrete layers of interacting growing protein seeds: convective and morphological stages of evolution.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {71}, number = {3 Pt 1}, pages = {031904}, doi = {10.1103/PhysRevE.71.031904}, pmid = {15903456}, issn = {1539-3755}, mesh = {Binding Sites ; Computer Simulation ; Crystallization/*methods ; *Evolution, Molecular ; *Models, Chemical ; *Models, Molecular ; Multiprotein Complexes/*chemistry/*ultrastructure ; Protein Binding ; Protein Conformation ; Proteins/*chemistry/*ultrastructure ; }, abstract = {The growth of several macromolecular seeds uniformly distributed on the bottom of a protein reactor (i.e., a discrete layer of N crystals embedded within a horizontal layer of liquid with no-slip boundaries) under microgravity conditions is investigated for different values of N and for two values of the geometrical aspect ratio of the container. The fluid dynamics of the growth reactor and the morphological (shape-change) evolution of the crystals are analyzed by means of a recently developed moving boundary method based on differential equations coming from the protein "surface incorporation kinetics." The face growth rates are found to depend on the complex multicellular structure of the convective field and on associated "pluming phenomena." This correspondence is indirect evidence of the fact that mass transport in the bulk and surface attachment kinetics are competitive as rate-limiting steps for growth. Significant adjustments in the roll pattern take place as time passes. The convective field undergoes an interesting sequence of transitions to different values of the mode and to different numbers of rising solutal jets. The structure of the velocity field and the solutal effects, in turn, exhibit sensitivity to the number of interacting crystals if this number is small. In the opposite case, a certain degree of periodicity can be highlighted for a core zone not affected by edge effects. The results with no-slip lateral walls are compared with those for periodic boundary conditions to assess the role played by geometrical constraints in determining edge effects and the wavelength selection process. The numerical method provides "microscopic" and "morphological" details as well as general rules and trends about the macroscopic evolution (i.e., "ensemble behaviors") of the system.}, } @article {pmid15893482, year = {2005}, author = {Csaba, G and Kovács, P and Pállinger, E}, title = {Hormonal interactions in Tetrahymena: effect of hormones on levels of epidermal growth factor (EGF).}, journal = {Cell biology international}, volume = {29}, number = {4}, pages = {301-305}, doi = {10.1016/j.cellbi.2005.01.004}, pmid = {15893482}, issn = {1065-6995}, mesh = {Animals ; Epidermal Growth Factor/*metabolism ; Flow Cytometry ; Histamine/pharmacology ; Hormones/*pharmacology ; Insulin/pharmacology ; Microscopy, Confocal ; Serotonin/pharmacology ; Tetrahymena pyriformis/*physiology ; }, abstract = {Tetrahymena pyriformiswas treated with insulin, histamine or serotonin for 30 min and epidermal growth factor (EGF) level was studied inside the cells using specific antibodies and flow cytometry as well as confocal microscopy. The EGF concentration was highly significantly elevated after hormone treatment, regardless of the hormone used. EGF was localized mainly in the cortical region (mucocysts) and in vesicles and this localization did not differ in untreated and treated cells. The results call attention to the possibility of interactions between hormones at unicellular level and points to the presence of a hormonal system in Tetrahymena that includes receptors, hormones and signal transduction pathways as well as hormonal interactions. This could be the basis of further evolution to the hormonal system of multicellulars.}, } @article {pmid15892118, year = {2005}, author = {Rodríguez-Trelles, F and Tarrío, R and Ayala, FJ}, title = {Is ectopic expression caused by deregulatory mutations or due to gene-regulation leaks with evolutionary potential?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {27}, number = {6}, pages = {592-601}, doi = {10.1002/bies.20241}, pmid = {15892118}, issn = {0265-9247}, support = {GM42397/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Choristoma/*genetics ; *Evolution, Molecular ; Gene Expression Regulation/*genetics ; Humans ; *Models, Genetic ; Mutation/*genetics ; Oligonucleotide Array Sequence Analysis ; }, abstract = {It has long been thought that gene expression is tightly regulated in multicellular eukaryotes, so that expression profiles match functional profiles. This conception emerged from the assumption that gene activity is synonymous with gene function. This paradigm was first challenged by comparative protein electrophoresis studies showing extensive differences in expression patterns among related species. The paradigm is now being challenged by evolutionary transcriptomics using microarray technologies. Most gene expression profiles display features that lack any obvious functional significance. The so-called "ectopic" expression refers to the expression of genes at times and locations where the target gene is not known to have a function. However, ectopic expression might be associated with genuine function even if this function is not essential or has yet to be ascertained. Alternatively, ectopic expression might come about as a superfluous by-product of regulatory systems, which would call for a revision of prevailing ideas about the specificity of gene regulation. We herein review available evidence for ectopic expression and the hypotheses proposed for its origin and evolution. We propose that ectopic expression must be regarded as part of an integrated phenotypic whole. It seems likely that ectopic expression represents a leak in the evolution of regulatory systems, but one that is endowed with considerable evolutionary possibilities.}, } @article {pmid15886873, year = {2004}, author = {Ponec, M and El Ghalbzouri, A and Dijkman, R and Kempenaar, J and van der Pluijm, G and Koolwijk, P}, title = {Endothelial network formed with human dermal microvascular endothelial cells in autologous multicellular skin substitutes.}, journal = {Angiogenesis}, volume = {7}, number = {4}, pages = {295-305}, doi = {10.1007/s10456-004-6315-3}, pmid = {15886873}, issn = {0969-6970}, mesh = {Base Sequence ; Cells, Cultured ; Coculture Techniques ; DNA Primers ; Endothelium, Vascular/*cytology/metabolism ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts/metabolism ; Humans ; Keratinocytes/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Skin/blood supply/*cytology/metabolism ; *Skin, Artificial ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {A human skin equivalent from a single skin biopsy harboring keratinocytes and melanocytes in the epidermal compartment, and fibroblasts and microvascular dermal endothelial cells in the dermal compartment was developed. The results of the study revealed that the nature of the extracellular matrix of the dermal compartments plays an important role in establishment of endothelial network in vitro. With rat-tail type I collagen matrices only lateral but not vertical expansion of endothelial networks was observed. In contrast, the presence of extracellular matrix of entirely human origin facilitated proper spatial organization of the endothelial network. Namely, when human dermal fibroblasts and microvascular endothelial cells were seeded on the bottom of an inert filter and subsequently epidermal cells were seeded on top of it, fibroblasts produced extracellular matrix throughout which numerous branched tubes were spreading three-dimensionally. Fibroblasts also facilitated the formation of basement membrane at the epidermal/matrix interface. Under all culture conditions, fully differentiated epidermis was formed with numerous melanocytes present in the basal epidermal cell layer. The results of the competitive RT-PCR revealed that both keratinocytes and fibroblasts expressed VEGF-A, -B, -C, aFGF and bFGF mRNA, whereas fibroblasts also expressed VEGF-D mRNA. At protein level, keratinocytes produced 10 times higher amounts of VEGF-A than fibroblasts did. The generation of multicellular skin equivalent from a single human skin biopsy will stimulate further developments for its application in the treatment of full-thickness skin defects. The potential development of biodegradable, biocompatible material suitable for these purposes is a great challenge for future research.}, } @article {pmid15883883, year = {2005}, author = {Caetano-Anollés, G and Caetano-Anollés, D}, title = {Universal sharing patterns in proteomes and evolution of protein fold architecture and life.}, journal = {Journal of molecular evolution}, volume = {60}, number = {4}, pages = {484-498}, pmid = {15883883}, issn = {0022-2844}, mesh = {*Evolution, Molecular ; *Life ; *Protein Folding ; Proteome ; }, abstract = {Protein evolution is imprinted in both the sequence and the structure of evolutionary building blocks known as protein domains. These domains share a common ancestry and can be unified into a comparatively small set of folding architectures, the protein folds. We have traced the distribution of protein folds between and within proteomes belonging to Eukarya, Archaea, and Bacteria along the branches of a universal phylogeny of protein architecture. This tree was reconstructed from global fold-usage statistics derived from a structural census of proteomes. We found that folds shared by the three organismal domains were placed almost exclusively at the base of the rooted tree and that there were marked heterogeneities in fold distribution and clear evolutionary patterns related to protein architecture and organismal diversification. These include a relative timing for the emergence of prokaryotes, congruent episodes of architectural loss and diversification in Archaea and Bacteria, and a late and quite massive rise of architectural novelties in Eukarya perhaps linked to multicellularity.}, } @article {pmid15883880, year = {2005}, author = {Gatherer, D and McEwan, NR}, title = {Phylogenetic differences in content and intensity of periodic proteins.}, journal = {Journal of molecular evolution}, volume = {60}, number = {4}, pages = {447-461}, pmid = {15883880}, issn = {0022-2844}, mesh = {*Phylogeny ; Proteins/classification/*genetics ; Proteome ; }, abstract = {Many proteins exhibit sequence periodicity, often correlated with a visible structural periodicity. The statistical significance of such periodicity can be assessed by means of a chi-squared-based test, with significance thresholds being calculated from shuffled sequences. Comparison of the complete proteomes of 45 species reveals striking differences in the proportion of periodic proteins and the intensity of the most significant periodicities. Eukaryotes tend to have a higher proportion of periodic proteins than eubacteria, which in turn tend to have more than archaea. The intensity of periodicity in the most periodic proteins is also greatest in eukaryotes. By contrast, the relatively small group of periodic proteins in archaea also tend to be weakly periodic compared to those of eukaryotes and eubacteria. Exceptions to this general rule are found in those prokaryotes with multicellular life-cycle phases, e.g., Methanosarcina sp., or Anabaena sp., which have more periodicities than prokaryotes in general, and in unicellular eukaryotes, which have fewer than multicellular eukaryotes. The distribution of significantly periodic proteins in eukaryotes is over a wide range of period lengths, whereas prokaryotic proteins typically have a more limited set of period lengths. This is further investigated by repeating the analysis on the NRL-3D database of proteins of solved structure. Some short-range periodicities are explicable in terms of basic secondary structure, e.g., alpha helices, while middle-range periodicities are frequently found to consist of known short Pfam domains, e.g., leucine-rich repeats, tetratricopeptides or armadillo domains. However, not all can be explained in this way.}, } @article {pmid15875012, year = {2005}, author = {Eichinger, L and Pachebat, JA and Glöckner, G and Rajandream, MA and Sucgang, R and Berriman, M and Song, J and Olsen, R and Szafranski, K and Xu, Q and Tunggal, B and Kummerfeld, S and Madera, M and Konfortov, BA and Rivero, F and Bankier, AT and Lehmann, R and Hamlin, N and Davies, R and Gaudet, P and Fey, P and Pilcher, K and Chen, G and Saunders, D and Sodergren, E and Davis, P and Kerhornou, A and Nie, X and Hall, N and Anjard, C and Hemphill, L and Bason, N and Farbrother, P and Desany, B and Just, E and Morio, T and Rost, R and Churcher, C and Cooper, J and Haydock, S and van Driessche, N and Cronin, A and Goodhead, I and Muzny, D and Mourier, T and Pain, A and Lu, M and Harper, D and Lindsay, R and Hauser, H and James, K and Quiles, M and Madan Babu, M and Saito, T and Buchrieser, C and Wardroper, A and Felder, M and Thangavelu, M and Johnson, D and Knights, A and Loulseged, H and Mungall, K and Oliver, K and Price, C and Quail, MA and Urushihara, H and Hernandez, J and Rabbinowitsch, E and Steffen, D and Sanders, M and Ma, J and Kohara, Y and Sharp, S and Simmonds, M and Spiegler, S and Tivey, A and Sugano, S and White, B and Walker, D and Woodward, J and Winckler, T and Tanaka, Y and Shaulsky, G and Schleicher, M and Weinstock, G and Rosenthal, A and Cox, EC and Chisholm, RL and Gibbs, R and Loomis, WF and Platzer, M and Kay, RR and Williams, J and Dear, PH and Noegel, AA and Barrell, B and Kuspa, A}, title = {The genome of the social amoeba Dictyostelium discoideum.}, journal = {Nature}, volume = {435}, number = {7038}, pages = {43-57}, pmid = {15875012}, issn = {1476-4687}, support = {/WT_/Wellcome Trust/United Kingdom ; MC_U105115237/MRC_/Medical Research Council/United Kingdom ; R01 HD035925/HD/NICHD NIH HHS/United States ; }, mesh = {ATP-Binding Cassette Transporters/genetics ; Animals ; Base Composition ; Cell Adhesion/genetics ; Cell Movement/genetics ; Centromere/genetics ; Conserved Sequence/genetics ; DNA Transposable Elements/genetics ; DNA, Ribosomal/genetics ; Dictyostelium/cytology/enzymology/*genetics/metabolism ; Eukaryotic Cells/metabolism ; Gene Duplication ; Gene Transfer, Horizontal/genetics ; *Genome ; *Genomics ; Humans ; Molecular Sequence Data ; Phylogeny ; Proteome ; Protozoan Proteins/chemistry/genetics ; RNA, Transfer/genetics ; Repetitive Sequences, Nucleic Acid/genetics ; Sequence Analysis, DNA ; Signal Transduction/genetics ; *Social Behavior ; Telomere/genetics ; }, abstract = {The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.}, } @article {pmid15852308, year = {2005}, author = {Handl, CH and Todt, C}, title = {Foregut glands of Solenogastres (mollusca): anatomy and revised terminology.}, journal = {Journal of morphology}, volume = {265}, number = {1}, pages = {28-42}, doi = {10.1002/jmor.10336}, pmid = {15852308}, issn = {0362-2525}, mesh = {Animals ; Digestive System/*ultrastructure ; Exocrine Glands/*ultrastructure ; Mollusca/*ultrastructure ; }, abstract = {In the molluscan class Solenogastres, different types of foregut glands vary in number, structure, and location within the foregut. The present article describes their anatomy and cytology and intends to clarify their confused terminology. Pharyngeal glands, esophageal glands, and the more complex dorsal and ventrolateral foregut glands can be distinguished. The ventrolateral foregut glands (ventral foregut glandular organs, ventral salivary glands of auct.), in the literature subdivided previously into four types, are revisited here in the context of current vertebrate gland terminology. The results of recent investigations are added to earlier ones, and a classification system for these multicellular glands is proposed. This system is based on cytological characters of glandular cells (intra- or extraepithelial), characters of the associated musculature (inner or outer musculature), location of the gland relative to the pharynx epithelium (endoepithelial or exoepithelial), characters of the gland openings (paired or unpaired), morphology of the gland duct (simple or branched), and some additional features like the arrangement of glandular cells along the gland ducts. Gross morphology and anatomy of ventrolateral foregut glands constitute useful taxonomic characters in determining higher taxa (family level), and finer details of the anatomy and cytology are useful in determining lower levels (genus and species). Possible pathways for the evolution of the different gland types of Solenogastres in relation to foregut glands present in the other molluscan clades are presented. The importance of ventrolateral foregut gland characters for phylogenetic considerations within the Solenogastres is discussed.}, } @article {pmid15851065, year = {2005}, author = {Brosius, J}, title = {Waste not, want not--transcript excess in multicellular eukaryotes.}, journal = {Trends in genetics : TIG}, volume = {21}, number = {5}, pages = {287-288}, doi = {10.1016/j.tig.2005.02.014}, pmid = {15851065}, issn = {0168-9525}, mesh = {Alternative Splicing/*genetics ; Animals ; Eukaryotic Cells/*physiology ; *Evolution, Molecular ; Gene Expression Regulation/*genetics ; *Genome ; Humans ; RNA Precursors/genetics ; RNA, Messenger/genetics ; RNA, Untranslated/*physiology ; Selection, Genetic ; *Transcription, Genetic ; }, abstract = {There is growing evidence that mammalian genomes produce thousands of transcripts that do not encode proteins, and this RNA class might even rival the complexity of mRNAs. There is no doubt that a number of these non-protein-coding RNAs have important regulatory functions in the cell. However, do all transcripts have a function or are many of them products of fortuitous transcription with no function? The second scenario is mirrored by numerous alternative-splicing events that lead to truncated proteins. Nevertheless, analogous to 'superfluous' genomic DNA, aberrant transcripts or processing products embody evolutionary potential and provide novel RNAs that natural selection can act on.}, } @article {pmid15833842, year = {2005}, author = {Burns, JS and Abdallah, BM and Guldberg, P and Rygaard, J and Schrøder, HD and Kassem, M}, title = {Tumorigenic heterogeneity in cancer stem cells evolved from long-term cultures of telomerase-immortalized human mesenchymal stem cells.}, journal = {Cancer research}, volume = {65}, number = {8}, pages = {3126-3135}, doi = {10.1158/0008-5472.CAN-04-2218}, pmid = {15833842}, issn = {0008-5472}, mesh = {Adult ; Animals ; Cell Transformation, Neoplastic/genetics/metabolism/*pathology ; Clone Cells ; Humans ; Mesenchymal Stem Cells/cytology/*enzymology/*pathology/physiology ; Mice ; Neoplastic Stem Cells/*enzymology/*pathology/physiology ; Spheroids, Cellular/enzymology/pathology ; Telomerase/genetics/*metabolism ; Time Factors ; Transduction, Genetic ; Transplantation, Heterologous ; }, abstract = {Long-term cultures of telomerase-transduced adult human mesenchymal stem cells (hMSC) may evolve spontaneous genetic changes leading to tumorigenicity in immunodeficient mice (e.g., hMSC-TERT20). We wished to clarify whether this unusual phenotype reflected a rare but dominant subpopulation or if the stem cell origin allowed most cells to behave as cancer stem cells. Cultures of the hMSC-TERT20 strain at population doubling 440 were highly clonogenic (94%). From 110 single-cell clones expanded by 20 population doublings, 6 underwent detailed comparison. Like the parental population, each clone had approximately 1.2 days doubling time with loss of contact inhibition. All retained 1,25-(OH)(2) vitamin D(3)-induced expression of osteoblastic markers: collagen type I, alkaline phosphatase, and osteocalcin. All shared INK4a/ARF gene locus deletion and epigenetic silencing of the DBCCR1 tumor suppressor gene. Despite in vitro commonality, only four of six clones shared the growth kinetics and 100% tumorigenicity of the parental population. In contrast, one clone consistently formed latent tumors and the other established tumors with only 30% penetrance. Changing the in vitro microenvironment to mimic in vivo growth aspects revealed concordant clonal heterogeneity. Latent tumor growth correlated with extracellular matrix entrapment of multicellular spheroids and high procollagen type III expression. Poor tumorigenicity correlated with in vitro serum dependence and high p27(Kip1) expression. Aggressive tumorigenicity correlated with good viability plus capillary morphogenesis on serum starvation and high cyclin D1 expression. Thus, hMSC-TERT20 clones represent cancer stem cells with hierarchical tumorigenicity, providing new models to explore the stem cell hypothesis for cancer.}, } @article {pmid15824443, year = {2005}, author = {Newman, SA}, title = {The pre-Mendelian, pre-Darwinian world: shifting relations between genetic and epigenetic mechanisms in early multicellular evolution.}, journal = {Journal of biosciences}, volume = {30}, number = {1}, pages = {75-85}, pmid = {15824443}, issn = {0250-5991}, mesh = {Animals ; *Biological Evolution ; *Epigenesis, Genetic ; Extremities/anatomy & histology/growth & development ; *Gene Expression Regulation, Developmental ; Morphogenesis ; }, abstract = {The reliable dependence of many features of contemporary organisms on changes in gene content and activity is tied to the processes of Mendelian inheritance and Darwinian evolution. With regard to morphological characters, however, Mendelian inheritance is the exception rather than the rule, and neo-Darwinian mechanisms in any case do not account for the origination (as opposed to the inherited variation) of such characters. It is proposed, therefore, that multicellular organisms passed through a pre-Mendelian, pre-Darwinian phase, whereby cells, genes and gene products constituted complex systems with context-dependent, self-organizing morphogenetic capabilities. An example is provided of a plausible 'core' mechanism for the development of the vertebrate limb that is both inherently pattern forming and morphogenetically plastic. It is suggested that most complex multicellular structures originated from such systems. The notion that genes are privileged determinants of biological characters can only be sustained by neglecting questions of evolutionary origination and the evolution of developmental mechanisms.}, } @article {pmid15818467, year = {2005}, author = {Römling, U}, title = {Characterization of the rdar morphotype, a multicellular behaviour in Enterobacteriaceae.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {62}, number = {11}, pages = {1234-1246}, pmid = {15818467}, issn = {1420-682X}, mesh = {Animals ; Biofilms/growth & development ; Cellulose/biosynthesis ; Cyclic GMP/*analogs & derivatives/metabolism ; *Enterobacteriaceae/cytology/growth & development/metabolism ; Escherichia coli Proteins ; Humans ; Models, Biological ; Phylogeny ; Trans-Activators/metabolism ; }, abstract = {The rdar morphotype, a multicellular behaviour of Salmonella enterica and Escherichia coli is characterized by the expression of the adhesive extracellular matrix components cellulose and curli fimbriae. The response regulator CsgD, which transcriptionally activates the biosynthesis of the exopolysaccharide cellulose and curli, also transforms cell physiology to the multicellular state. However, the only role of CsgD in cellulose biosynthesis is the activation of AdrA, a GGDEF domain protein that mediates production of the allosteric activator cyclic-di-(3'-5')guanylic acid (c-di-GMP). In S. enterica serovar Typhimurium a regulatory network consisting of 19 GGDEF/EAL domain-containing proteins tightly controls the concentration of c-di-GMP. c-di-GMP not only regulates the expression of cellulose, but also stimulates expression of adhesive curli and represses various modes of motility. Functions of characterized GGDEF and EAL domain proteins, as well as database searches, point to a global role for c-di-GMP as a novel secondary messenger that regulates a variety of cellular functions in response to diverse environmental stimuli already in the deepest roots of the prokaryotes.}, } @article {pmid15809433, year = {2005}, author = {Baer, CF and Shaw, F and Steding, C and Baumgartner, M and Hawkins, A and Houppert, A and Mason, N and Reed, M and Simonelic, K and Woodard, W and Lynch, M}, title = {Comparative evolutionary genetics of spontaneous mutations affecting fitness in rhabditid nematodes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {102}, number = {16}, pages = {5785-5790}, pmid = {15809433}, issn = {0027-8424}, support = {F32 GM020887/GM/NIGMS NIH HHS/United States ; R01 GM036827/GM/NIGMS NIH HHS/United States ; 1F32 GM 20887-01/GM/NIGMS NIH HHS/United States ; R01 GM 36827/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Genetic Variation ; *Mutation ; Rhabditida/*genetics/*physiology ; }, abstract = {Deleterious mutations are of fundamental importance to all aspects of organismal biology. Evolutionary geneticists have expended tremendous effort to estimate the genome-wide rate of mutation and the effects of new mutations on fitness, but the degree to which genomic mutational properties vary within and between taxa is largely unknown, particularly in multicellular organisms. Beginning with two highly inbred strains from each of three species in the nematode family Rhabditidae (Caenorhabditis briggsae, Caenorhabditis elegans, and Oscheius myriophila), we allowed mutations to accumulate in the relative absence of natural selection for 200 generations. We document significant variation in the rate of decay of fitness because of new mutations between strains and between species. Estimates of the per-generation mutational decay of fitness were very consistent within strains between assays 100 generations apart. Rate of mutational decay in fitness was positively associated with genomic mutation rate and negatively associated with average mutational effect. These results provide unambiguous experimental evidence for substantial variation in genome-wide properties of mutation both within and between species and reinforce conclusions from previous experiments that the cumulative effects on fitness of new mutations can differ markedly among related taxa.}, } @article {pmid15802665, year = {2005}, author = {Panchin, YV}, title = {Evolution of gap junction proteins--the pannexin alternative.}, journal = {The Journal of experimental biology}, volume = {208}, number = {Pt 8}, pages = {1415-1419}, doi = {10.1242/jeb.01547}, pmid = {15802665}, issn = {0022-0949}, mesh = {Amino Acid Sequence ; Animals ; Brain/physiology ; Cell Communication/genetics/*physiology ; Connexins/*genetics/physiology ; *Evolution, Molecular ; Molecular Sequence Data ; Multigene Family/genetics/physiology ; Nerve Tissue Proteins ; Phylogeny ; Protein Conformation ; Sequence Alignment ; Vertebrates/genetics/*physiology ; }, abstract = {Gap junctions provide one of the most common forms of intercellular communication. They are composed of membrane proteins that form a channel that is permeable to ions and small molecules, connecting the cytoplasm of adjacent cells. Gap junctions serve similar functions in all multicellular animals (Metazoa). Two unrelated protein families are involved in this function; connexins, which are found only in chordates, and pannexins, which are ubiquitous and present in both chordate and invertebrate genomes. The involvement of mammalian pannexins to gap junction formation was recently confirmed. Now it is necessary to consider the role of pannexins as an alternative to connexins in vertebrate intercellular communication.}, } @article {pmid15795378, year = {2005}, author = {Koide, T and Hayata, T and Cho, KW}, title = {Xenopus as a model system to study transcriptional regulatory networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {102}, number = {14}, pages = {4943-4948}, pmid = {15795378}, issn = {0027-8424}, support = {R01 HD029507/HD/NICHD NIH HHS/United States ; HD29507/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; DNA/genetics ; Endoderm/cytology ; Gene Expression Regulation, Developmental ; Genes, Regulator ; Genomics ; Intercellular Signaling Peptides and Proteins ; Mesoderm/cytology ; Models, Genetic ; Oligonucleotide Array Sequence Analysis ; Phylogeny ; Promoter Regions, Genetic ; Proteins/genetics ; Signal Transduction ; Transcription, Genetic ; Transcriptional Activation ; Xenopus/*embryology/*genetics ; Xenopus Proteins ; }, abstract = {Development is controlled by a complex series of events requiring sequential gene activation. Understanding the logic of gene networks during development is necessary for a complete understanding of how genes contribute to phenotype. Pioneering work initiated in the sea urchin and Drosophila has demonstrated that reasonable transcriptional regulatory network diagrams representing early development in multicellular animals can be generated through use of appropriate genomic, genetic, and biochemical tools. Establishment of similar regulatory network diagrams for vertebrate development is a necessary step. The amphibian Xenopus has long been used as a model for vertebrate early development and has contributed greatly to the elucidation of gene regulation. Because the best and most extensively studied transcriptional regulatory network in Xenopus is that underlying the formation and function of Spemann's organizer, we describe the current status of our understanding of this gene regulatory network and its relationship to mesodermal patterning. Seventy-four transcription factors currently known to be expressed in the mesoendoderm of Xenopus gastrula were characterized according to their modes of action, DNA binding consensus sequences, and target genes. Among them, nineteen transcription factors were characterized sufficiently in detail, allowing us to generate a gene regulatory network diagram. Additionally, we discuss recent amphibian work using a combined DNA microarray and bioinformatics approach that promises to accelerate regulatory network studies.}, } @article {pmid15790593, year = {2005}, author = {Gissen, P and Johnson, CA and Gentle, D and Hurst, LD and Doherty, AJ and O'Kane, CJ and Kelly, DA and Maher, ER}, title = {Comparative evolutionary analysis of VPS33 homologues: genetic and functional insights.}, journal = {Human molecular genetics}, volume = {14}, number = {10}, pages = {1261-1270}, doi = {10.1093/hmg/ddi137}, pmid = {15790593}, issn = {0964-6906}, mesh = {Amino Acid Sequence ; Animals ; Conserved Sequence ; Cytoplasmic Vesicles/physiology ; DNA-Binding Proteins/genetics/physiology ; Drosophila Proteins/genetics/physiology ; Drosophila melanogaster/genetics/physiology ; Evolution, Molecular ; Eye Proteins/genetics/physiology ; Humans ; Membrane Proteins/*genetics/physiology ; Mice ; Molecular Sequence Data ; Proteins/*genetics/physiology ; Rats ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/*genetics ; Sequence Alignment ; Sequence Homology ; Vesicular Transport Proteins/*genetics ; }, abstract = {VPS33B protein is a homologue of the yeast class C vacuolar protein sorting protein Vps33p that is involved in the biogenesis and function of vacuoles. Vps33p homologues contain a Sec1 domain and belong to the family of Sec1/Munc18 (SM) proteins that regulate fusion of membrane-bound organelles and interact with other vps proteins and also SNARE proteins that execute membrane fusion in all cells. We demonstrated recently that mutations in VPS33B cause ARC syndrome (MIM 208085), a lethal multisystem disease. In contrast, mutations in other Vps33p homologues result in different phenotypes, e.g. a mutation in Drosophila melanogaster car gene causes the carnation eye colour mutant and inactivation of mouse Vps33a causes buff hypopigmentation phenotype. In mammals two Vps33p homologues (e.g. VPS33A and VPS33B in humans) have been identified. As comparative genome analysis can provide novel insights into gene evolution and function, we performed nucleotide and protein sequence comparisons of Vps33 homologues in different species to define their inter-relationships and evolution. In silico analysis (a) identified two homologues of yeast Vps33p in the worm, fly, zebrafish, rodent and human genomes, (b) suggested that Carnation is an orthologue of VPS33A rather than VPS33B and (c) identified conserved candidate functional domains within VPS33B. We have shown previously that wild-type VPS33B induced perinuclear clustering of late endosomes and lysosomes in human renal cells. Consistent with the predictions of comparative analysis: (a) VPS33B induced significantly more clustering than VPS33A in a renal cell line, (b) a putative fly VPS33B homologue but not Carnation protein also induced clustering and (c) the ability to induce clustering in renal cells was linked to two evolutionary conserved domains within VPS33B. One domain was present in VPS33B but not VPS33A homologues and the other was one of three regions predicted to form a t-SNARE binding site in VPS33B. In contrast, VPS33A induced significantly more clustering of melanosomes in melanoma cells than VPS33B. These investigations are consistent with the hypothesis that there are two functional classes of Vps33p homologues in all multicellular organisms and that the two classes reflect the evolution of organelle/tissue-specific functions.}, } @article {pmid15788102, year = {2005}, author = {Wuchty, S and Almaas, E}, title = {Evolutionary cores of domain co-occurrence networks.}, journal = {BMC evolutionary biology}, volume = {5}, number = {}, pages = {24}, pmid = {15788102}, issn = {1471-2148}, mesh = {Animals ; Cluster Analysis ; Computational Biology ; Databases, Protein ; *Evolution, Molecular ; Genomics ; Humans ; Models, Genetic ; Models, Statistical ; Protein Binding ; *Protein Interaction Mapping ; Protein Structure, Tertiary ; Proteins/chemistry ; Proteomics/methods ; Saccharomyces cerevisiae/metabolism ; Sequence Analysis, Protein ; Signal Transduction ; Species Specificity ; }, abstract = {BACKGROUND: The modeling of complex systems, as disparate as the World Wide Web and the cellular metabolism, as networks has recently uncovered a set of generic organizing principles: Most of these systems are scale-free while at the same time modular, resulting in a hierarchical architecture. The structure of the protein domain network, where individual domains correspond to nodes and their co-occurrences in a protein are interpreted as links, also falls into this category, suggesting that domains involved in the maintenance of increasingly developed, multicellular organisms accumulate links. Here, we take the next step by studying link based properties of the protein domain co-occurrence networks of the eukaryotes S. cerevisiae, C. elegans, D. melanogaster, M. musculus and H. sapiens.

RESULTS: We construct the protein domain co-occurrence networks from the PFAM database and analyze them by applying a k-core decomposition method that isolates the globally central (highly connected domains in the central cores) from the locally central (highly connected domains in the peripheral cores) protein domains through an iterative peeling process. Furthermore, we compare the subnetworks thus obtained to the physical domain interaction network of S. cerevisiae. We find that the innermost cores of the domain co-occurrence networks gradually grow with increasing degree of evolutionary development in going from single cellular to multicellular eukaryotes. The comparison of the cores across all the organisms under consideration uncovers patterns of domain combinations that are predominately involved in protein functions such as cell-cell contacts and signal transduction. Analyzing a weighted interaction network of PFAM domains of yeast, we find that domains having only a few partners frequently interact with these, while the converse is true for domains with a multitude of partners. Combining domain co-occurrence and interaction information, we observe that the co-occurrence of domains in the innermost cores (globally central domains) strongly coincides with physical interaction. The comparison of the multicellular eukaryotic domain co-occurrence networks with the single celled of S. cerevisiae (the overlap network) uncovers small, connected network patterns.

CONCLUSION: We hypothesize that these patterns, consisting of the domains and links preserved through evolution, may constitute nucleation kernels for the evolutionary increase in proteome complexity. Combining co-occurrence and physical interaction data we argue that the driving force behind domain fusions is a collective effect caused by the number of interactions and not the individual interaction frequency.}, } @article {pmid15781713, year = {2005}, author = {Force, A and Cresko, WA and Pickett, FB and Proulx, SR and Amemiya, C and Lynch, M}, title = {The origin of subfunctions and modular gene regulation.}, journal = {Genetics}, volume = {170}, number = {1}, pages = {433-446}, pmid = {15781713}, issn = {0016-6731}, support = {5F32GM020892/GM/NIGMS NIH HHS/United States ; 2R15GM061620-02/GM/NIGMS NIH HHS/United States ; R24 RR014085/RR/NCRR NIH HHS/United States ; R15 GM061620/GM/NIGMS NIH HHS/United States ; U01 HG002526/HG/NHGRI NIH HHS/United States ; RR14085/RR/NCRR NIH HHS/United States ; F32 GM020892/GM/NIGMS NIH HHS/United States ; HG02526-01/HG/NHGRI NIH HHS/United States ; }, mesh = {Biological Evolution ; Data Interpretation, Statistical ; Enhancer Elements, Genetic ; Gene Expression Regulation/*physiology ; Genetic Variation ; *Models, Genetic ; Mutation ; Population ; Transcription Factors/*physiology ; }, abstract = {Evolutionary explanations for the origin of modularity in genetic and developmental pathways generally assume that modularity confers a selective advantage. However, our results suggest that even in the absence of any direct selective advantage, genotypic modularity may increase through the formation of new subfunctions under near-neutral processes. Two subfunctions may be formed from a single ancestral subfunction by the process of fission. Subfunction fission occurs when multiple functions under unified genetic control become subdivided into more restricted functions under independent genetic control. Provided that population size is sufficiently small, random genetic drift and mutation can conspire to produce changes in the number of subfunctions in the genome of a species without necessarily altering the phenotype. Extensive genotypic modularity may then accrue in a near-neutral fashion in permissive population-genetic environments, potentially opening novel pathways to morphological evolution. Many aspects of gene complexity in multicellular eukaryotes may have arisen passively as population size reductions accompanied increases in organism size, with the adaptive exploitation of such complexity occurring secondarily.}, } @article {pmid15766530, year = {2005}, author = {Lai, ZC and Wei, X and Shimizu, T and Ramos, E and Rohrbaugh, M and Nikolaidis, N and Ho, LL and Li, Y}, title = {Control of cell proliferation and apoptosis by mob as tumor suppressor, mats.}, journal = {Cell}, volume = {120}, number = {5}, pages = {675-685}, doi = {10.1016/j.cell.2004.12.036}, pmid = {15766530}, issn = {0092-8674}, support = {GM20293/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing ; Animals ; Apoptosis/*physiology ; Cell Line ; *Cell Proliferation ; Cell Transformation, Neoplastic/genetics/*metabolism ; Conserved Sequence ; DNA, Complementary/analysis/genetics ; Drosophila ; Drosophila Proteins/genetics/isolation & purification/*metabolism ; Evolution, Molecular ; Gene Expression Regulation, Developmental/genetics ; Humans ; Membrane Proteins/genetics/metabolism ; Mice ; Microscopy, Electron, Scanning ; Molecular Sequence Data ; Mutation/genetics ; Neoplasms/genetics/*metabolism ; Nerve Tissue Proteins/genetics/metabolism ; Protein Kinases/*metabolism ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Transferases (Other Substituted Phosphate Groups) ; Tumor Suppressor Proteins/genetics/isolation & purification/*metabolism ; }, abstract = {Appropriate cell number and organ size in a multicellular organism are determined by coordinated cell growth, proliferation, and apoptosis. Disruption of these processes can cause cancer. Recent studies have identified the Large tumor suppressor (Lats)/Warts (Wts) protein kinase as a key component of a pathway that controls the coordination between cell proliferation and apoptosis. Here we describe growth inhibitory functions for a Mob superfamily protein, termed Mats (Mob as tumor suppressor), in Drosophila. Loss of Mats function results in increased cell proliferation, defective apoptosis, and induction of tissue overgrowth. We show that mats and wts function in a common pathway. Mats physically associates with Wts to stimulate the catalytic activity of the Wts kinase. A human Mats ortholog (Mats1) can rescue the lethality associated with loss of Mats function in Drosophila. As Mats1 is mutated in human tumors, Mats-mediated growth inhibition and tumor suppression is likely conserved in humans.}, } @article {pmid15757677, year = {2005}, author = {Takagi, H and Kaneko, K}, title = {Dynamical systems basis of metamorphosis: diversity and plasticity of cellular states in reaction diffusion network.}, journal = {Journal of theoretical biology}, volume = {234}, number = {2}, pages = {173-186}, doi = {10.1016/j.jtbi.2004.11.030}, pmid = {15757677}, issn = {0022-5193}, mesh = {Animals ; Cell Communication/physiology ; Cell Death/physiology ; Cell Differentiation/physiology ; Cell Division/physiology ; Metamorphosis, Biological/*physiology ; *Models, Biological ; *Systems Theory ; }, abstract = {Dynamics maintaining diversity of cell types in a multi-cellular system are studied in relation to the plasticity of cellular states. By adopting a simple theoretical framework for intra-cellular chemical reaction dynamics and considering the division and death of cells, the development of cells is studied. Cell differentiation process is found to occur through instability in transient dynamics and cell-cell interaction. In long-term behavior, extinction of multiple cells is repeated, which leads to itinerancy over successive quasi-stable multi-cellular states consisting of different types of cells. By defining the plasticity of a cellular state, it is shown that the plasticity of cells decreases before the extinction of most cell types, from which diversity and plasticity are later recovered. In the following, a decrease of plasticity occurs again, leading to the next extinction. This cycle of diversification and extinction is repeated. Relevance of our results to development and evolution is briefly discussed.}, } @article {pmid15740615, year = {2005}, author = {Rivero, F and Muramoto, T and Meyer, AK and Urushihara, H and Uyeda, TQ and Kitayama, C}, title = {A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa.}, journal = {BMC genomics}, volume = {6}, number = {}, pages = {28}, pmid = {15740615}, issn = {1471-2164}, mesh = {Actin Cytoskeleton ; Actins/chemistry ; Amino Acid Sequence ; Animals ; Caenorhabditis elegans ; Carrier Proteins/chemistry ; DNA, Complementary/metabolism ; Databases, Protein ; Dictyostelium/*metabolism ; Drosophila ; Fungal Proteins/*chemistry ; Gene Expression Regulation ; Humans ; Microfilament Proteins/chemistry ; Molecular Sequence Data ; Phylogeny ; Protein Isoforms ; Protein Structure, Tertiary ; Reverse Transcriptase Polymerase Chain Reaction ; Saccharomyces cerevisiae/metabolism ; Schizosaccharomyces/metabolism ; Sequence Analysis, DNA/*methods ; Sequence Homology, Amino Acid ; }, abstract = {BACKGROUND: Formins are multidomain proteins defined by a conserved FH2 (formin homology 2) domain with actin nucleation activity preceded by a proline-rich FH1 (formin homology 1) domain. Formins act as profilin-modulated processive actin nucleators conserved throughout a wide range of eukaryotes.

RESULTS: We present a detailed sequence analysis of the 10 formins (ForA to J) identified in the genome of the social amoeba Dictyostelium discoideum. With the exception of ForI and ForC all other formins conform to the domain structure GBD/FH3-FH1-FH2-DAD, where DAD is the Diaphanous autoinhibition domain and GBD/FH3 is the Rho GTPase-binding domain/formin homology 3 domain that we propose to represent a single domain. ForC lacks a FH1 domain, ForI lacks recognizable GBD/FH3 and DAD domains and ForA, E and J have additional unique domains. To establish the relationship between formins of Dictyostelium and other organisms we constructed a phylogenetic tree based on the alignment of FH2 domains. Real-time PCR was used to study the expression pattern of formin genes. Expression of forC, D, I and J increased during transition to multi-cellular stages, while the rest of genes displayed less marked developmental variations. During sexual development, expression of forH and forI displayed a significant increase in fusion competent cells.

CONCLUSION: Our analysis allows some preliminary insight into the functionality of Dictyostelium formins: all isoforms might display actin nucleation activity and, with the exception of ForI, might also be susceptible to autoinhibition and to regulation by Rho GTPases. The architecture GBD/FH3-FH1-FH2-DAD appears common to almost all Dictyostelium, fungal and metazoan formins, for which we propose the denomination of conventional formins, and implies a common regulatory mechanism.}, } @article {pmid15737066, year = {2005}, author = {Froissart, R and Roze, D and Uzest, M and Galibert, L and Blanc, S and Michalakis, Y}, title = {Recombination every day: abundant recombination in a virus during a single multi-cellular host infection.}, journal = {PLoS biology}, volume = {3}, number = {3}, pages = {e89}, pmid = {15737066}, issn = {1545-7885}, mesh = {Caulimovirus/genetics/pathogenicity ; Genetic Markers ; *Genome, Viral ; Models, Genetic ; Plant Diseases/virology ; Plant Viruses/genetics ; *Recombination, Genetic ; Restriction Mapping ; *Virus Diseases ; Viruses/*genetics/pathogenicity ; }, abstract = {Viral recombination can dramatically impact evolution and epidemiology. In viruses, the recombination rate depends on the frequency of genetic exchange between different viral genomes within an infected host cell and on the frequency at which such co-infections occur. While the recombination rate has been recently evaluated in experimentally co-infected cell cultures for several viruses, direct quantification at the most biologically significant level, that of a host infection, is still lacking. This study fills this gap using the cauliflower mosaic virus as a model. We distributed four neutral markers along the viral genome, and co-inoculated host plants with marker-containing and wild-type viruses. The frequency of recombinant genomes was evaluated 21 d post-inoculation. On average, over 50% of viral genomes recovered after a single host infection were recombinants, clearly indicating that recombination is very frequent in this virus. Estimates of the recombination rate show that all regions of the genome are equally affected by this process. Assuming that ten viral replication cycles occurred during our experiment-based on data on the timing of coat protein detection-the per base and replication cycle recombination rate was on the order of 2 x 10(-5) to 4 x 10(-5). This first determination of a virus recombination rate during a single multi-cellular host infection indicates that recombination is very frequent in the everyday life of this virus.}, } @article {pmid15734655, year = {2005}, author = {Graczyk, TK}, title = {Is Giardia a living fossil?.}, journal = {Trends in parasitology}, volume = {21}, number = {3}, pages = {104-107}, doi = {10.1016/j.pt.2005.01.002}, pmid = {15734655}, issn = {1471-4922}, mesh = {Animals ; Eukaryotic Cells/physiology ; *Evolution, Molecular ; Giardia/*genetics ; Host-Parasite Interactions ; Mitochondria/metabolism ; Oxygen/metabolism ; Phylogeny ; Prokaryotic Cells/physiology ; Symbiosis/physiology ; }, abstract = {Despite enormous efforts, the patterns of the rise of eukaryotic life on Earth are not clearly defined. The ability of eukaryotes to produce energy using oxygen and sugars was a key factor in advancing life on Earth towards complex multicellular organisms. However, this was not the only way to produce energy and survive. Mitochondria probably appeared soon after the oxygen increase in the Earth's atmosphere but many microaerophilic protists require little or no oxygen to survive. New ultrastructural, biochemical and molecular phylogeny data about structures and processes involved in the generation of energy by currently known protists have forced the revision of understanding of the "tree of life".}, } @article {pmid15731334, year = {2005}, author = {Matter, N and König, H}, title = {Targeted 'knockdown' of spliceosome function in mammalian cells.}, journal = {Nucleic acids research}, volume = {33}, number = {4}, pages = {e41}, pmid = {15731334}, issn = {1362-4962}, mesh = {Animals ; Cell Line, Tumor ; Humans ; Jurkat Cells ; Mice ; Oligoribonucleotides, Antisense/*pharmacology ; *RNA Splicing/drug effects ; RNA, Small Nuclear/*antagonists & inhibitors/physiology ; Spliceosomes/drug effects/*physiology ; }, abstract = {The existence of two sophisticated parallel splicing machineries in multicellular organisms has raised intriguing questions--ranging from their impact on proteome expansion to the evolution of splicing and of metazoan genomes. Exploring roles for the distinct splicing systems in vivo has, however, been restricted by the lack of techniques to selectively inhibit their function in cells. In this study, we show that morpholino oligomers complementary to the branch-site recognition elements of U2 or U12 small nuclear RNA specifically suppress the function of the two splicing systems in mammalian cells. The data provide the first evidence for a role of distinct spliceosomes in pre-mRNA splicing from endogenous mammalian genes and establish a tool to define roles for the different splicing machineries in vivo.}, } @article {pmid15714559, year = {2005}, author = {Kirk, DL}, title = {A twelve-step program for evolving multicellularity and a division of labor.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {27}, number = {3}, pages = {299-310}, doi = {10.1002/bies.20197}, pmid = {15714559}, issn = {0265-9247}, mesh = {Animals ; *Biological Evolution ; Cell Division/*physiology ; Chlamydomonas reinhardtii/classification ; Chlorophyta/classification/ultrastructure ; Eukaryota/classification ; Phylogeny ; }, abstract = {The volvocine algae provide an unrivalled opportunity to explore details of an evolutionary pathway leading from a unicellular ancestor to multicellular organisms with a division of labor between different cell types. Members of this monophyletic group of green flagellates range in complexity from unicellular Chlamydomonas through a series of extant organisms of intermediate size and complexity to Volvox, a genus of spherical organisms that have thousands of cells and a germ-soma division of labor. It is estimated that these organisms all shared a common ancestor about 50 +/- 20 MYA. Here we outline twelve important ways in which the developmental repertoire of an ancestral unicell similar to modern C. reinhardtii was modified to produce first a small colonial organism like Gonium that was capable of swimming directionally, then a sequence of larger organisms (such as Pandorina, Eudorina and Pleodorina) in which there was an increasing tendency to differentiate two cell types, and eventually Volvox carteri with its complete germ-soma division of labor.}, } @article {pmid15703239, year = {2005}, author = {Lavrov, DV and Forget, L and Kelly, M and Lang, BF}, title = {Mitochondrial genomes of two demosponges provide insights into an early stage of animal evolution.}, journal = {Molecular biology and evolution}, volume = {22}, number = {5}, pages = {1231-1239}, doi = {10.1093/molbev/msi108}, pmid = {15703239}, issn = {0737-4038}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; DNA, Mitochondrial/*genetics ; Genetic Code ; *Genome ; Introns ; Invertebrates/*genetics ; Mitochondria/*genetics ; Molecular Sequence Data ; Phylogeny ; Porifera/*genetics ; RNA, Ribosomal/*genetics ; RNA, Transfer/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {Mitochondrial DNA (mtDNA) of multicellular animals (Metazoa) is typically a small (approximately 16 kbp), circular-mapping molecule that encodes 37 tightly packed genes. The structures of mtDNA-encoded transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs) are usually highly unorthodox, and proteins are translated with multiple deviations from the standard genetic code. In contrast, mtDNA of the choanoflagellate Monosiga brevicollis, the closest unicellular relative of animals, is four times larger, contains 1.5 times as many genes, and lacks mentioned peculiarities of animal mtDNA. To investigate the evolutionary transition that led to the specific organization of metazoan mtDNA, we determined complete mitochondrial sequences from the demosponges Geodia neptuni and Tethya actinia, two representatives of the most basal animal phylum, the Porifera. We found that poriferan mtDNAs resemble those of other animals in their compact organization, lack of introns, and a well-conserved animal-like gene order. Yet, they contain several extra genes, encode bacterial-like rRNAs and tRNAs, and use a minimally derived genetic code. Our findings suggest that the evolution of the typical metazoan mtDNA has been a multistep process in which the compact genome organization and the reduced gene content were established prior to the reduction of tRNA and rRNA structures and the introduction of multiple changes of the translation code.}, } @article {pmid15693956, year = {2005}, author = {Holmes, DI and Zachary, I}, title = {The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease.}, journal = {Genome biology}, volume = {6}, number = {2}, pages = {209}, pmid = {15693956}, issn = {1474-760X}, mesh = {Alternative Splicing ; Amino Acid Sequence ; Evolution, Molecular ; Humans ; Molecular Sequence Data ; Neovascularization, Pathologic/etiology ; Protein Structure, Tertiary ; Vascular Endothelial Growth Factors/chemistry/*genetics/*physiology ; }, abstract = {Vascular endothelial growth factors (VEGFs) are a family of secreted polypeptides with a highly conserved receptor-binding cystine-knot structure similar to that of the platelet-derived growth factors. VEGF-A, the founding member of the family, is highly conserved between animals as evolutionarily distant as fish and mammals. In vertebrates, VEGFs act through a family of cognate receptor kinases in endothelial cells to stimulate blood-vessel formation. VEGF-A has important roles in mammalian vascular development and in diseases involving abnormal growth of blood vessels; other VEGFs are also involved in the development of lymphatic vessels and disease-related angiogenesis. Invertebrate homologs of VEGFs and VEGF receptors have been identified in fly, nematode and jellyfish, where they function in developmental cell migration and neurogenesis. The existence of VEGF-like molecules and their receptors in simple invertebrates without a vascular system indicates that this family of growth factors emerged at a very early stage in the evolution of multicellular organisms to mediate primordial developmental functions.}, } @article {pmid15686618, year = {2005}, author = {Singh, SR and Chen, X and Hou, SX}, title = {JAK/STAT signaling regulates tissue outgrowth and male germline stem cell fate in Drosophila.}, journal = {Cell research}, volume = {15}, number = {1}, pages = {1-5}, doi = {10.1038/sj.cr.7290255}, pmid = {15686618}, issn = {1001-0602}, support = {Z99 CA999999//Intramural NIH HHS/United States ; }, mesh = {Animals ; Body Patterning ; Cell Line ; Cell Lineage ; Cell Movement ; Cell Proliferation ; DNA-Binding Proteins/*physiology ; Drosophila ; Humans ; Janus Kinase 1 ; MAP Kinase Signaling System ; Male ; Models, Biological ; Protein-Tyrosine Kinases/*physiology ; STAT1 Transcription Factor ; Signal Transduction ; Stem Cells/*cytology ; Tissue Distribution ; Trans-Activators/*physiology ; }, abstract = {In multicellular organisms, biological activities are regulated by cell signaling. The various signal transduction pathways regulate cell fate, proliferation, migration, and polarity. Miscoordination of the communicative signals will lead to disasters like cancer and other fatal diseases. The JAK/STAT signal transduction pathway is one of the pathways, which was first identified in vertebrates and is highly conserved throughout evolution. Studying the JAK/STAT signal transduction pathway in Drosophila provides an excellent opportunity to understand the molecular mechanism of the cell regulation during development and tumor formation. In this review, we discuss the general overview of JAK/STAT signaling in Drosophila with respect to its functions in the eye development and stem cell fate determination.}, } @article {pmid15666350, year = {2005}, author = {Shapiro, JA}, title = {Retrotransposons and regulatory suites.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {27}, number = {2}, pages = {122-125}, doi = {10.1002/bies.20192}, pmid = {15666350}, issn = {0265-9247}, mesh = {Animals ; Blastocyst ; Cell Differentiation ; DNA, Complementary/metabolism ; Exons ; Gene Expression Regulation ; *Gene Expression Regulation, Developmental ; Gene Library ; Genome ; Models, Genetic ; Oocytes/metabolism ; RNA/chemistry ; Retroelements/genetics/*physiology ; }, abstract = {Cellular differentiation and multicellular development require the programmed expression of coregulated suites of genetic loci dispersed throughout the genome. How do functionally diverse loci come to share common regulatory motifs? A new paper finds that retrotransposons (RTEs) may play a role in providing common regulation to a group of functions expressed during the development of oocytes and preimplantation embryos. Examining cDNA libraries, Peaston et al. find that 13% of all processed transcripts in full-grown mouse oocytes contain RTE sequences, mostly from the MT family of retroviral-like elements. Smaller but still significant percentages of RTE sequences are found in cDNA libraries from 2-cell embryos and blastocysts. A quarter of these RTE sequences are at the 5' ends of chimeric transcripts that also contain exons from endogenous mouse loci. These chimeric transcripts display restricted expression in oocytes and preimplantation embryos and presumably originate from developmentally regulated LTR promoters. Some, but not all, chimeric transcripts encode novel protein products.}, } @article {pmid15662424, year = {2005}, author = {Lieberman, E and Hauert, C and Nowak, MA}, title = {Evolutionary dynamics on graphs.}, journal = {Nature}, volume = {433}, number = {7023}, pages = {312-316}, doi = {10.1038/nature03204}, pmid = {15662424}, issn = {1476-4687}, mesh = {*Biological Evolution ; Ecology ; Genetic Drift ; *Models, Biological ; Mutation/genetics ; Population Dynamics ; Probability ; Reproduction/physiology ; Selection, Genetic ; Stochastic Processes ; }, abstract = {Evolutionary dynamics have been traditionally studied in the context of homogeneous or spatially extended populations. Here we generalize population structure by arranging individuals on a graph. Each vertex represents an individual. The weighted edges denote reproductive rates which govern how often individuals place offspring into adjacent vertices. The homogeneous population, described by the Moran process, is the special case of a fully connected graph with evenly weighted edges. Spatial structures are described by graphs where vertices are connected with their nearest neighbours. We also explore evolution on random and scale-free networks. We determine the fixation probability of mutants, and characterize those graphs for which fixation behaviour is identical to that of a homogeneous population. Furthermore, some graphs act as suppressors and others as amplifiers of selection. It is even possible to find graphs that guarantee the fixation of any advantageous mutant. We also study frequency-dependent selection and show that the outcome of evolutionary games can depend entirely on the structure of the underlying graph. Evolutionary graph theory has many fascinating applications ranging from ecology to multi-cellular organization and economics.}, } @article {pmid15659557, year = {2005}, author = {Collins, L and Penny, D}, title = {Complex spliceosomal organization ancestral to extant eukaryotes.}, journal = {Molecular biology and evolution}, volume = {22}, number = {4}, pages = {1053-1066}, doi = {10.1093/molbev/msi091}, pmid = {15659557}, issn = {0737-4038}, mesh = {Eukaryotic Cells ; Introns ; Phylogeny ; RNA, Messenger/genetics ; *Spliceosomes ; }, abstract = {In higher eukaryotes, introns are spliced out of protein-coding mRNAs by the spliceosome, a massive complex comprising five non-coding RNAs (ncRNAs) and about 200 proteins. By comparing the differences between spliceosomal proteins from many basal eukaryotic lineages, it is possible to infer properties of the splicing system in the last common ancestor of extant eukaryotes, the eukaryotic ancestor. We begin with the hypothesis that, similar to intron length (that appears to have increased in multicellular eukaryotes), the spliceosome has increased in complexity throughout eukaryotic evolution. However, examination of the distribution of spliceosomal components indicates that not only was a spliceosome present in the eukaryotic ancestor but it also contained most of the key components found in today's eukaryotes. All the small nuclear ribonucleoproteins (snRNPs) protein components are likely to have been present, as well as many splicing-related proteins. Both major and trans-splicing are likely to have been present, and the spliceosome had already formed links with other cellular processes such as transcription and capping. However, there is no evidence as yet to suggest that minor (U12-dependent) splicing was present in the eukaryotic ancestor. Although the last common ancestor of extant eukaryotes appears to show much of the molecular complexity seen today, we do not, from this work, infer anything of the properties of the earlier "first eukaryote."}, } @article {pmid15653558, year = {2005}, author = {Gehring, WJ}, title = {New perspectives on eye development and the evolution of eyes and photoreceptors.}, journal = {The Journal of heredity}, volume = {96}, number = {3}, pages = {171-184}, doi = {10.1093/jhered/esi027}, pmid = {15653558}, issn = {0022-1503}, mesh = {Animals ; Brain/embryology/metabolism ; *Evolution, Molecular ; Eye/embryology/*metabolism/ultrastructure ; Eye Proteins/*genetics ; *Gene Expression Regulation, Developmental ; Genetics, Population ; Homeodomain Proteins/*genetics ; Microscopy, Electron, Scanning ; Models, Genetic ; PAX6 Transcription Factor ; Paired Box Transcription Factors/*genetics ; Photoreceptor Cells/cytology/*metabolism/ultrastructure ; Repressor Proteins/*genetics ; }, abstract = {Recent experiments on the genetic control of eye development have opened up a completely new perspective on eye evolution. The demonstration that targeted expression of one and the same master control gene, that is, Pax6 can induce the formation of ectopic eyes in both insects and vertebrates, necessitates a reconsideration of the dogma of a polyphyletic origin of the various eye types in all the animal phyla. The involvement of Pax6 and six1 and six3 genes, which encode highly conserved transcription factors, in the genetic control of eye development in organisms ranging from planarians to humans argues strongly for a monophyletic origin of the eye. Because transcription factors can control the expression of any target gene provided it contains the appropriate gene regulatory elements, the conservation of the genetic control of eye development by Pax6 among all bilaterian animals is not due to functional constraints but a consequence of its evolutionary history. The prototypic eyes postulated by Darwin to consist of two cells only, a photoreceptor and a pigment cell, were accidentally controlled by Pax6 and the subsequent evolution of the various eye types occurred by building onto this original genetic program. A hypothesis of intercalary evolution is proposed that assumes that the eye morphogenetic pathway is progressively modified by intercalation of genes between the master control genes on the top of the hierarchy and the structural genes like rhodopsin at the bottom. The recruitment of novel genes into the eye morphogenetic pathway can be due to at least two different genetic mechanisms, gene duplication and enhancer fusion.In tracing back the evolution of eyes beyond bilaterians, we find highly developed eyes in some box-jellyfish as well as in some Hydrozoans. In Hydrozoans the same orthologous six genes (six1 and six3) are required for eye regeneration as in planarians, and in the box jellyfish Tripedalia a pax B gene, which may be a precursor of Pax6, was found to be expressed in the eyes. In contrast to the adults, which have highly evolved eyes, the Planula larva of Tripedalia has single- celled photoreceptors similar to some unicellular protists. For the origin of photoreceptor cells in metazoa, I propose two hypotheses, one based on cellular differentiation and a more speculative one based on symbiosis. The former assumes that photoreceptor cells originated from a colonial protist in which all the cells were photosensitive and subsequent cellular differentiation to give rise to photoreceptor cells. The symbiont hypothesis, which I call the Russian doll model, assumes that photosensitivity arose first in photosynthetic cyanobacteria that were subsequently taken up into red algae as primary chloroplasts. The red algae in turn were taken up by dinoflagellates as secondary chloroplasts and in some species evolved into the most sophisticated eye organelles, as found, for example, in some dinoflagellates like Erythropsis and Warnovia, which lack chloroplasts. Because dinoflagellates are commonly found as symbionts in cnidarians, the dinoflagellates may have transferred their photoreceptor genes to cnidarians. In cnidarians such as Tripedalia the step from photoreceptor organelles to multicellular eyes has occurred. These two hypotheses, the cellular differentiation and the symbiont hypothesis, are not mutually exclusive and are the subject of further investigations.}, } @article {pmid15650739, year = {2005}, author = {Kusserow, A and Pang, K and Sturm, C and Hrouda, M and Lentfer, J and Schmidt, HA and Technau, U and von Haeseler, A and Hobmayer, B and Martindale, MQ and Holstein, TW}, title = {Unexpected complexity of the Wnt gene family in a sea anemone.}, journal = {Nature}, volume = {433}, number = {7022}, pages = {156-160}, doi = {10.1038/nature03158}, pmid = {15650739}, issn = {1476-4687}, mesh = {Animals ; Bayes Theorem ; Cloning, Molecular ; Embryonic Development/genetics ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Intercellular Signaling Peptides and Proteins/*genetics/metabolism ; Molecular Sequence Data ; Multigene Family/*genetics ; Phylogeny ; RNA, Messenger/genetics/metabolism ; Sea Anemones/embryology/*genetics ; Sequence Alignment ; Wnt Proteins ; }, abstract = {The Wnt gene family encodes secreted signalling molecules that control cell fate in animal development and human diseases. Despite its significance, the evolution of this metazoan-specific protein family is unclear. In vertebrates, twelve Wnt subfamilies were defined, of which only six have counterparts in Ecdysozoa (for example, Drosophila and Caenorhabditis). Here, we report the isolation of twelve Wnt genes from the sea anemone Nematostella vectensis, a species representing the basal group within cnidarians. Cnidarians are diploblastic animals and the sister-group to bilaterian metazoans. Phylogenetic analyses of N. vectensis Wnt genes reveal a thus far unpredicted ancestral diversity within the Wnt family. Cnidarians and bilaterians have at least eleven of the twelve known Wnt gene subfamilies in common; five subfamilies appear to be lost in the protostome lineage. Expression patterns of Wnt genes during N. vectensis embryogenesis indicate distinct roles of Wnts in gastrulation, resulting in serial overlapping expression domains along the primary axis of the planula larva. This unexpectedly complex inventory of Wnt family signalling factors evolved in early multi-cellular animals about 650 million years (Myr) ago, predating the Cambrian explosion by at least 100 Myr (refs 5, 8). It emphasizes the crucial function of Wnt genes in the diversification of eumetazoan body plans.}, } @article {pmid15647795, year = {2004}, author = {Cottage, A and Mullan, L and Portela, MB and Hellen, E and Carver, T and Patel, S and Vavouri, T and Elgar, G and Edwards, YJ}, title = {Molecular characterisation of the SAND protein family: a study based on comparative genomics, structural bioinformatics and phylogeny.}, journal = {Cellular & molecular biology letters}, volume = {9}, number = {4A}, pages = {739-753}, pmid = {15647795}, issn = {1425-8153}, mesh = {Amino Acid Sequence ; Animals ; Computational Biology ; Fungi/genetics ; Genomics ; Humans ; Lysosomes/genetics ; Molecular Sequence Data ; *Phylogeny ; Plants/genetics ; Protein Structure, Secondary ; SNARE Proteins ; Sequence Alignment ; Sequence Homology, Amino Acid ; Vacuoles/genetics ; Vesicular Transport Proteins/*chemistry/classification/*genetics ; }, abstract = {The activities of vertebrate lysosomes are critical to many essential cellular processes. The yeast vacuole is analogous to the mammalian lysosome and is used as a tool to gain insights into vesicle mediated vacuolar/lysosome transport. The protein SAND, which does not contain a SAND domain (PFAM accession number PF01342), has recently been shown to function at the tethering/docking stage of vacuole fusion as a critical component of the vacuole SNARE complex. In this publication we have identified SAND in diverse eukaryotes, from single celled organisms such as the yeasts to complex multi-cellular chordates such as mammals. We have demonstrated subfamily divisions in the SAND proteins and show that in vertebrates, a duplication event gave rise to two SAND sequences. This duplication appears to have occurred during early vertebrate evolution and conceivably with the evolution of lysosomes. Using bioinformatics we predict a secondary structure, solvent accessibility profile and protein fold for the SAND proteins and determine conserved sequence motifs, present in all SAND proteins and those that are specific to subsets. A comprehensive evaluation of yeast and human functional studies in conjunction with our in silico analysis has identified potential roles for some of these motifs.}, } @article {pmid15642091, year = {2005}, author = {Sano, R and Juárez, CM and Hass, B and Sakakibara, K and Ito, M and Banks, JA and Hasebe, M}, title = {KNOX homeobox genes potentially have similar function in both diploid unicellular and multicellular meristems, but not in haploid meristems.}, journal = {Evolution & development}, volume = {7}, number = {1}, pages = {69-78}, doi = {10.1111/j.1525-142X.2005.05008.x}, pmid = {15642091}, issn = {1520-541X}, mesh = {Arabidopsis/*genetics ; Arabidopsis Proteins/chemistry ; Cell Lineage ; Cloning, Molecular ; DNA, Complementary/metabolism ; *Diploidy ; *Gene Expression Regulation, Plant ; *Genes, Homeobox ; Genes, Plant ; *Haploidy ; Homeodomain Proteins/genetics ; In Situ Hybridization ; Meristem/*physiology ; Models, Genetic ; Phenotype ; Phylogeny ; Plant Proteins/chemistry ; RNA/metabolism ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Members of the class 1 knotted-like homeobox (KNOX) gene family are important regulators of shoot apical meristem development in angiosperms. To determine whether they function similarly in seedless plants, three KNOX genes (two class 1 genes and one class 2 gene) from the fern Ceratopteris richardii were characterized. Expression of both class 1 genes was detected in the shoot apical cell, leaf primordia, marginal part of the leaves, and vascular bundles by in situ hybridization, a pattern that closely resembles that of class 1 KNOX genes in angiosperms with compound leaves. The fern class 2 gene was expressed in all sporophyte tissues examined, which is characteristic of class 2 gene expression in angiosperms. All three CRKNOX genes were not detected in gametophyte tissues by RNA gel blot analysis. Arabidopsis plants overexpressing the fern class 1 genes resembled plants that overexpress seed plant class 1 KNOX genes in leaf morphology. Ectopic expression of the class 2 gene in Arabidopsis did not result in any unusual phenotypes. Taken together with phylogenetic analysis, our results suggest that (a) the class 1 and 2 KNOX genes diverged prior to the divergence of fern and seed plant lineages, (b) the class 1 KNOX genes function similarly in seed plant and fern sporophyte meristem development despite their differences in structure, (c) KNOX gene expression is not required for the development of the fern gametophyte, and (d) the sporophyte and gametophyte meristems of ferns are not regulated by the same developmental mechanisms at the molecular level.}, } @article {pmid15640810, year = {2005}, author = {Brookfield, JF}, title = {The ecology of the genome - mobile DNA elements and their hosts.}, journal = {Nature reviews. Genetics}, volume = {6}, number = {2}, pages = {128-136}, doi = {10.1038/nrg1524}, pmid = {15640810}, issn = {1471-0056}, mesh = {Animals ; DNA Transposable Elements/*genetics ; *Ecology ; *Evolution, Molecular ; *Genome ; Humans ; }, abstract = {The genomes of multicellular eukaryotes provide information that determines the phenotype. However, not all sequences in the genome are required for this purpose. Other sequences are often selfish in their actions and interact in complex ways. Here, an analogy is developed between the components of the genome, including mobile DNA elements, and an ecological community. Unlike ecological communities, however, the slow rates at which genomes change allow us to reconstruct patterns of interaction that stretch back tens or hundreds of millions of years.}, } @article {pmid15625190, year = {2005}, author = {Webb, CJ and Romfo, CM and van Heeckeren, WJ and Wise, JA}, title = {Exonic splicing enhancers in fission yeast: functional conservation demonstrates an early evolutionary origin.}, journal = {Genes & development}, volume = {19}, number = {2}, pages = {242-254}, pmid = {15625190}, issn = {0890-9369}, mesh = {Animals ; Avian Sarcoma Viruses/genetics ; Chickens/genetics ; *Evolution, Molecular ; Humans ; Immunoglobulin M/genetics ; Mice ; Protein Binding/genetics/physiology ; RNA Splicing/*genetics/physiology ; RNA Splicing Factors ; RNA, Messenger/*genetics/metabolism ; RNA-Binding Proteins/*genetics/metabolism ; Schizosaccharomyces/*genetics/physiology ; Schizosaccharomyces pombe Proteins/*genetics/metabolism ; Two-Hybrid System Techniques ; }, abstract = {Discrete sequence elements known as exonic splicing enhancers (ESEs) have been shown to influence both the efficiency of splicing and the profile of mature mRNAs in multicellular eukaryotes. While the existence of ESEs has not been demonstrated previously in unicellular eukaryotes, the factors known to recognize these elements and mediate their communication with the core splicing machinery are conserved and essential in the fission yeast Schizosaccharomyces pombe. Here, we provide evidence that ESE function is conserved through evolution by demonstrating that three exonic splicing enhancers derived from vertebrates (chicken ASLV, mouse IgM, and human cTNT) promote splicing of two distinct S. pombe pre-messenger RNAs (pre-mRNAs). Second, as in extracts from mammalian cells, ESE function in S. pombe is compromised by mutations and increased distance from the 3'-splice site. Third, three-hybrid analyses indicate that the essential SR (serine/arginine-rich) protein Srp2p, but not the dispensable Srp1p, binds specifically to both native and heterologous purine-rich elements; thus, Srp2p is the likely mediator of ESE function in fission yeast. Finally, we have identified five natural purine-rich elements from S. pombe that promote splicing of our reporter pre-mRNAs. Taken together, these results provide strong evidence that the genesis of ESE-mediated splicing occurred early in eukaryotic evolution.}, } @article {pmid15621521, year = {2005}, author = {Sorensen, EB and Mesner, PW}, title = {IgH-2 cells: a reptilian model for apoptotic studies.}, journal = {Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology}, volume = {140}, number = {1}, pages = {163-170}, doi = {10.1016/j.cbpc.2004.10.001}, pmid = {15621521}, issn = {1096-4959}, mesh = {Animals ; *Apoptosis ; Caspase Inhibitors ; Caspases/metabolism ; Cell Nucleus/drug effects/metabolism/*ultrastructure ; Cells, Cultured/drug effects/metabolism/radiation effects ; Chromatin/drug effects/ultrastructure ; Enzyme Inhibitors/pharmacology ; Heart/drug effects/physiology ; Iguanas/*metabolism ; *Models, Biological ; Phosphatidylserines/metabolism ; Ultraviolet Rays ; }, abstract = {Regulation of proper cell number in tissues depends upon a balance between cell proliferation and cell death. The process of apoptosis has thus far been studied in a variety of multicellular organisms from humans to higher plants. In order to broaden our perspective and identify another metazoan system with which to deepen our understanding of the function and evolution of the apoptotic machinery, we have characterized cell death in a reptilian cell line. We show that the death of IgH-2 Iguana (Iguana iguana) heart cells [Clark, H.F., Cohen, M.M., Karzon, D.T., 1970. Characterization of reptilian cell lines established at incubation temperatures of 23 to 36 degrees. Proc. Soc. Exp. Biol. Med. 133, 1039-1047.] is, in response to DNA damaging agents, accompanied by classic morphological changes of apoptosis including detachment from the substrate, cell shrinkage, nuclear pyknosis and externalization of the plasma membrane phospholipid phosphatidylserine. Our biochemical studies show that the death of IgH-2 cells is accompanied by internucleosomal DNA fragmentation and activation of caspases. Our studies with the pan-caspase inhibitor zVAD.fmk implicate caspases in the apoptotic process we observe. This work represents the first detailed molecular and biochemical analysis of apoptosis in cells of an organism of class Reptilia and establishes IgH-2 cells as a suitable model system with which to investigate the phenomenon of caspase dependent apoptosis and the apoptotic machinery in a reptilian model.}, } @article {pmid15596456, year = {2005}, author = {Kapraun, DF}, title = {Nuclear DNA content estimates in multicellular green, red and brown algae: phylogenetic considerations.}, journal = {Annals of botany}, volume = {95}, number = {1}, pages = {7-44}, pmid = {15596456}, issn = {0305-7364}, mesh = {Cell Nucleus/genetics ; Chlorophyta/*genetics ; DNA/*genetics ; *Genome ; Microspectrophotometry ; Phaeophyta/*genetics ; Phylogeny ; Rhodophyta/*genetics ; }, abstract = {BACKGROUND AND AIMS: Multicellular eukaryotic algae are phylogenetically disparate. Nuclear DNA content estimates have been published for fewer than 1 % of the described species of Chlorophyta, Phaeophyta and Rhodophyta. The present investigation aims to summarize the state of our knowledge and to add substantially to our database of C-values for theses algae.

METHODS: The DNA-localizing fluorochrome DAPI (4', 6-diamidino-2-phenylindole) and RBC (chicken erythrocyte) standard were used to estimate 2C values with static microspectrophotometry.

KEY RESULTS: 2C DNA contents for 85 species of Chlorophyta range from 0.2-6.1 pg, excluding the highly polyploidy Charales and Desmidiales with DNA contents of up to 39.2 and 20.7 pg, respectively. 2C DNA contents for 111 species of Rhodophyta range from 0.1-2.8 pg, and for 44 species of Phaeophyta range from 0.2-1.8 pg.

CONCLUSIONS: New availability of consensus higher-level molecular phylogenies provides a framework for viewing C-value data in a phylogenetic context. Both DNA content ranges and mean values are greater in taxa considered to be basal. It is proposed that the basal, ancestral genome in each algal group was quite small. Both mechanistic and ecological processes are discussed that could have produced the observed C-value ranges.}, } @article {pmid15576487, year = {2004}, author = {Li, Y and Kelly, WG and Logsdon, JM and Schurko, AM and Harfe, BD and Hill-Harfe, KL and Kahn, RA}, title = {Functional genomic analysis of the ADP-ribosylation factor family of GTPases: phylogeny among diverse eukaryotes and function in C. elegans.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {18}, number = {15}, pages = {1834-1850}, doi = {10.1096/fj.04-2273com}, pmid = {15576487}, issn = {1530-6860}, support = {R01 GM067226/GM/NIGMS NIH HHS/United States ; R01 GM068029/GM/NIGMS NIH HHS/United States ; }, mesh = {ADP-Ribosylation Factors/*classification/genetics/*physiology ; Animals ; Caenorhabditis elegans/*embryology/*enzymology/genetics ; Eukaryotic Cells/enzymology ; Genomics ; Green Fluorescent Proteins/metabolism ; Membrane Proteins/classification ; *Phylogeny ; RNA Interference ; }, abstract = {ADP-ribosylation factor (Arf) and Arf-like (Arl) proteins are a family of highly conserved 21 kDa GTPases that emerged early in the evolution of eukaryotes. These proteins serve regulatory roles in vesicular traffic, lipid metabolism, microtubule dynamics, development, and likely other cellular processes. We found evidence for the presence of 6 Arf family members in the protist Giardia lamblia and 22 members in mammals. A phylogenetic analysis was performed to delineate the evolutionary relationships among Arf family members and to attempt to organize them by both their evolutionary origins and functions in cells and/or organisms. The approximately 100 protein sequences analyzed from animals, fungi, plants, and protists clustered into 11 groups, including Arfs, nine Arls, and Sar proteins. To begin functional analyses of the family in a metazoan model organism, we examined roles for all three C. elegans Arfs (Arf-1, Arf-3, and Arf-6) and three Arls (Arl-1, Arl-2, and Arl-3) by use of RNA-mediated interference (RNAi). Injection of double-stranded RNA (dsRNA) encoding Arf-1 or Arf-3 into N2 hermaphrodites produced embryonic lethality in their offspring and, later, sterility in the injected animals themselves. Injection of Arl-2 dsRNA resulted in a disorganized germline and sterility in early offspring, with later offspring exhibiting an early embryonic arrest. Thus, of the six Arf family members examined in C. elegans, at least three are required for embryogenesis. These data represent the first analysis of the role(s) of multiple members of this family in the development of a multicellular organism.}, } @article {pmid15572453, year = {2004}, author = {Kauffman, S and Peterson, C and Samuelsson, B and Troein, C}, title = {Genetic networks with canalyzing Boolean rules are always stable.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {101}, number = {49}, pages = {17102-17107}, pmid = {15572453}, issn = {0027-8424}, mesh = {Animals ; *Cell Communication ; Humans ; Logic ; *Models, Theoretical ; Statistical Distributions ; Yeasts ; }, abstract = {We determine stability and attractor properties of random Boolean genetic network models with canalyzing rules for a variety of architectures. For all power law, exponential, and flat in-degree distributions, we find that the networks are dynamically stable. Furthermore, for architectures with few inputs per node, the dynamics of the networks is close to critical. In addition, the fraction of genes that are active decreases with the number of inputs per node. These results are based upon investigating ensembles of networks using analytical methods. Also, for different in-degree distributions, the numbers of fixed points and cycles are calculated, with results intuitively consistent with stability analysis; fewer inputs per node implies more cycles, and vice versa. There are hints that genetic networks acquire broader degree distributions with evolution, and hence our results indicate that for single cells, the dynamics should become more stable with evolution. However, such an effect is very likely compensated for by multicellular dynamics, because one expects less stability when interactions among cells are included. We verify this by simulations of a simple model for interactions among cells.}, } @article {pmid15568984, year = {2004}, author = {Gray, MW and Lang, BF and Burger, G}, title = {Mitochondria of protists.}, journal = {Annual review of genetics}, volume = {38}, number = {}, pages = {477-524}, doi = {10.1146/annurev.genet.37.110801.142526}, pmid = {15568984}, issn = {0066-4197}, mesh = {Animals ; Bacteria/genetics ; *Biological Evolution ; Cell Lineage ; DNA, Mitochondrial/*genetics ; Eukaryota/genetics ; *Eukaryotic Cells ; Fungi/genetics ; Gene Expression ; Mitochondria/*genetics/metabolism/physiology ; Phylogeny ; Plants/genetics ; Proteomics ; }, abstract = {Over the past several decades, our knowledge of the origin and evolution of mitochondria has been greatly advanced by determination of complete mitochondrial genome sequences. Among the most informative mitochondrial genomes have been those of protists (primarily unicellular eukaryotes), some of which harbor the most gene-rich and most eubacteria-like mitochondrial DNAs (mtDNAs) known. Comparison of mtDNA sequence data has provided insights into the radically diverse trends in mitochondrial genome evolution exhibited by different phylogenetically coherent groupings of eukaryotes, and has allowed us to pinpoint specific protist relatives of the multicellular eukaryotic lineages (animals, plants, and fungi). This comparative genomics approach has also revealed unique and fascinating aspects of mitochondrial gene expression, highlighting the mitochondrion as an evolutionary playground par excellence.}, } @article {pmid15565108, year = {2004}, author = {Allen, E and Xie, Z and Gustafson, AM and Sung, GH and Spatafora, JW and Carrington, JC}, title = {Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana.}, journal = {Nature genetics}, volume = {36}, number = {12}, pages = {1282-1290}, doi = {10.1038/ng1478}, pmid = {15565108}, issn = {1061-4036}, mesh = {Arabidopsis/*genetics ; Base Pairing ; Base Sequence ; Bayes Theorem ; *Evolution, Molecular ; *Gene Duplication ; MicroRNAs/*genetics ; *Models, Genetic ; Molecular Sequence Data ; *Phylogeny ; RNA Processing, Post-Transcriptional ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {MicroRNAs (miRNAs) in plants and animals function as post-transcriptional regulators of target genes, many of which are involved in multicellular development. miRNAs guide effector complexes to target mRNAs through base-pair complementarity, facilitating site-specific cleavage or translational repression. Biogenesis of miRNAs involves nucleolytic processing of a precursor transcript with extensive foldback structure. Here, we provide evidence that genes encoding miRNAs in plants originated by inverted duplication of target gene sequences. Several recently evolved genes encoding miRNAs in Arabidopsis thaliana and other small RNA-generating loci possess the hallmarks of inverted duplication events that formed the arms on each side of their respective foldback precursors. We propose a model for miRNA evolution that suggests a mechanism for de novo generation of new miRNA genes with unique target specificities.}, } @article {pmid15556303, year = {2004}, author = {Jost, W and Baur, A and Nick, P and Reski, R and Gorr, G}, title = {A large plant beta-tubulin family with minimal C-terminal variation but differences in expression.}, journal = {Gene}, volume = {340}, number = {1}, pages = {151-160}, doi = {10.1016/j.gene.2004.06.009}, pmid = {15556303}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Bryopsida/*genetics ; Cloning, Molecular ; DNA, Plant/chemistry/genetics ; Exons ; *Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Introns ; Molecular Sequence Data ; Multigene Family/*genetics ; Phylogeny ; Protein Isoforms/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Tubulin/*genetics ; }, abstract = {Tubulins, as the major structural component of microtubules (MT), are highly conserved throughout the entire eukaryotic kingdom. They consist of alpha/beta heterodimers. Both monomers, at least in multicellular organisms, are encoded by gene families. In higher plants up to eight beta-tubulin isotypes, mostly differing in their very C-termini, have been described. These variable beta-tubulin C-termini have been discussed in the context of functional microtubule diversity. However, in plants, in contrast to vertebrates, functional isotype specificity remains yet to be demonstrated. Unlike higher plants, unicellular green algae in general do not exhibit isotypic variations. The moss Physcomitrella patens is a phylogenetic intermediate between higher plants and green algae. We isolated six beta-tubulin genes from Physcomitrella, named PpTub1 to 6. We show that the exon/intron structure, with the exception of one additional intron in PpTub6, is identical with that of higher plants, and that some members of the family are differentially expressed. Moreover, we find that all Physcomitrella isotypes are highly conserved and, most strikingly, are almost identical within their C-terminal amino acids (aa). This evolutionary ancient and large beta-tubulin gene family without significant isotypic sequence variation points to a role of differential regulation in the evolution of plant tubulin isotypes.}, } @article {pmid15554238, year = {2004}, author = {Bock, KW and Köhle, C}, title = {Coordinate regulation of drug metabolism by xenobiotic nuclear receptors: UGTs acting together with CYPs and glucuronide transporters.}, journal = {Drug metabolism reviews}, volume = {36}, number = {3-4}, pages = {595-615}, doi = {10.1081/dmr-200033455}, pmid = {15554238}, issn = {0360-2532}, mesh = {Animals ; Cytochrome P-450 Enzyme System/*metabolism ; Glucuronides/*metabolism ; Glucuronosyltransferase/genetics/*metabolism ; Humans ; Receptors, Cytoplasmic and Nuclear/*metabolism ; Xenobiotics/*metabolism ; }, abstract = {Xenobiotic nuclear receptors (PXR, CAR, and the Ah receptor) coordinately induce genes involved in all phases of xenobiotic metabolism including oxidative metabolism, conjugation, and transport. The comment--dedicated to honor the memory of Herbert Remmer, mentor of the author K. W. B.--discusses mechanistic, functional, and evolutionary aspects of xenobiotic nuclear receptors which induce UGTs together with CYPs and glucuronide transporters in human and rodent liver and intestine. Recent findings on regulation of CYPs, UGTs, and transporters suggest that while nuclear receptor signaling induces different CYPs, regulation may converge on single UGTs and transporters. Functional consequences of co-regulation are discussed using examples from the metabolism of xeno- and endobiotics (drugs, bilirubin, bile salts, steroid hormones, and carcinogens). Animal-plant interactions may have been a major driving force in the evolutionary divergence of CYPs and UGTs in mammals and insects as well as in their regulation by nuclear receptors. In addition, regulation by nuclear receptors was probably shaped by the need for homeostatic control of endobiotic signals in the evolution of multicellular organisms.}, } @article {pmid15534818, year = {2004}, author = {Reppel, M and Pillekamp, F and Lu, ZJ and Halbach, M and Brockmeier, K and Fleischmann, BK and Hescheler, J}, title = {Microelectrode arrays: a new tool to measure embryonic heart activity.}, journal = {Journal of electrocardiology}, volume = {37 Suppl}, number = {}, pages = {104-109}, doi = {10.1016/j.jelectrocard.2004.08.033}, pmid = {15534818}, issn = {0022-0736}, mesh = {Action Potentials/physiology ; Alloys/chemistry ; Animals ; Arrhythmias, Cardiac/physiopathology ; Artifacts ; Electric Impedance ; Electrocardiography/drug effects/*instrumentation ; Equipment Design ; Heart/drug effects/*embryology ; Mice ; *Microelectrodes ; Myocytes, Cardiac/physiology ; Patch-Clamp Techniques/instrumentation ; Pharmacology ; Titanium/chemistry ; }, abstract = {The analysis of the sequential excitation of cardiac tissue is of high relevance, both for clinical pathophysiological purposes, eg, detection of sustained ventricular arrhythmias, as well as for experimental electrophysiology. Clinically, different technical approaches such as single electrode measurements and bipolar mapping electrode catheters have been used. In experimental setups several techniques to record cardiac activity have been proposed. Beside the well-established intracellular current-clamp recordings of action potentials, recent studies have performed extracellularly activation sequence mapping or simultaneous multichannel action potential electrode array measurements. Measurement of extracellularly recorded field potentials (FPs) hereby especially provides detailed information about the origin and spread of excitation in the heart. A similar analytical approach for cardiac FPs advanced the analysis of excitation spread and arrhythmic activity in multicellular preparations like developmental differentiation tissue of mouse embryonic stem cells, multicellular preparations of isolated native embryonic cardiomyocytes or the embryonic heart in toto. The use of substrate-integrated Microelectrode Arrays (MEAs, Multi Channel Systems, Reutlingen, Germany) with 60 electrodes of 10-30 microm diameters on a 100-200 microm grid, coated with porous titanium nitride to minimize the impedance allows recording of FPs at a high signal to noise ratio. The possibility to electrically stimulate the tissue further expands the range of applications and bioassays. It may thus facilitate the evaluation of drug research providing detailed information about the interplay of the complex cardiac network, and might improve the predictability of physiological and pathophysiological conditions or drug effects in embryonic heart tissue.}, } @article {pmid15533638, year = {2005}, author = {Robinson, DH}, title = {Pleomorphic mammalian tumor-derived bacteria self-organize as multicellular mammalian eukaryotic-like organisms: morphogenetic properties in vitro, possible origins, and possible roles in mammalian 'tumor ecologies'.}, journal = {Medical hypotheses}, volume = {64}, number = {1}, pages = {177-185}, doi = {10.1016/j.mehy.2004.04.023}, pmid = {15533638}, issn = {0306-9877}, mesh = {Animals ; Cell Communication/genetics ; Dogs ; Gene Transfer Techniques ; Genetic Vectors ; Lymphoma/genetics/*microbiology ; Spheroids, Cellular/*pathology ; Staphylococcus epidermidis/*cytology/genetics/*growth & development ; Symbiosis/genetics ; Tumor Cells, Cultured ; }, abstract = {Highly pleomorphic bacteria have regularly been isolated from mammalian tumors and leukemic bloods. Here, it is shown that highly pleomorphic, cell-wall deficient bacteria derived from a mammalian tumor self-organize in vitro into mammalian tissue-like morphogenetic patterns consisting of multicellular tissue-like sheets and capillary-like networks. It is proposed that these pleomorphic mammalian tumor-derived (MTD) bacteria, during morphogenesis, express mammalian tissue morphogenesis-related genes that were acquired through eukaryote-to-prokaryote DNA transfer. Similar pleomorphic MTD bacteria might play important roles as symbiotic multicellular mammalian eukaryotic-like organisms in mammalian 'tumor ecologies' that include malignant and nonmalignant mammalian eukaryotic cells. From a mammalian tumor ecology perspective, eradication of tumors in some mammalian hosts may depend upon the elimination of pleomorphic MTD bacteria self-organized as symbiotic multicellular mammalian eukaryotic-like organisms. Further investigations of the extraordinary mammalian eukaryotic-like multicellularity of these bacteria may yield fundamental insights into the evolution of multicellularity and multicellular development and may challenge basic assumptions regarding cellular evolution.}, } @article {pmid15522508, year = {2004}, author = {Keim, CN and Martins, JL and Abreu, F and Rosado, AS and de Barros, HL and Borojevic, R and Lins, U and Farina, M}, title = {Multicellular life cycle of magnetotactic prokaryotes.}, journal = {FEMS microbiology letters}, volume = {240}, number = {2}, pages = {203-208}, doi = {10.1016/j.femsle.2004.09.035}, pmid = {15522508}, issn = {0378-1097}, mesh = {Brazil ; Cell Division ; DNA, Bacterial/chemistry/isolation & purification ; DNA, Ribosomal/chemistry/isolation & purification ; Deltaproteobacteria/classification/*cytology/isolation & purification/*physiology ; Genes, rRNA ; Geologic Sediments/microbiology ; Microscopy, Electron ; Molecular Sequence Data ; Phylogeny ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Seawater/microbiology ; Sequence Analysis, DNA ; *Water Microbiology ; }, abstract = {Most multicellular organisms, prokaryotes as well as animals, plants, and algae have a unicellular stage in their life cycle. Here, we describe an uncultured prokaryotic magnetotactic multicellular organism that reproduces by binary fission. It is multicellular in all the stages of its life cycle, and during most of the life cycle the cells organize into a hollow sphere formed by a functionally coordinated and polarized single-cell layer that grows by increasing the cell size. Subsequently, all the cells divide synchronously; the organism becomes elliptical, and separates into two equal spheres with a torsional movement in the equatorial plane. Unicellular bacteria similar to the cells that compose these organisms have not been found. Molecular biology analysis showed that all the organisms studied belong to a single genetic population phylogenetically related to many-celled magnetotactic prokaryotes in the delta sub-group of the proteobacteria. This appears to be the first report of a multicellular prokaryotic organism that proliferates by dividing into two equal multicellular organisms each similar to the parent one.}, } @article {pmid15521448, year = {2004}, author = {Bonner, JT}, title = {Perspective: the size-complexity rule.}, journal = {Evolution; international journal of organic evolution}, volume = {58}, number = {9}, pages = {1883-1890}, doi = {10.1111/j.0014-3820.2004.tb00476.x}, pmid = {15521448}, issn = {0014-3820}, mesh = {Animals ; *Biological Evolution ; *Body Size ; *Cell Differentiation ; Humans ; *Models, Biological ; Social Environment ; Species Specificity ; }, abstract = {It is widely accepted that bigger entities have a greater division of labor than smaller ones and this is reflected in the fact that larger multicellular organisms have a corresponding increase in the number of their cell types. This rule is examined in some detail from very small organisms to large animals, and plants, and societies. Compared to other size-related rules, the size-complexity rule is relatively rough and approximate, yet clearly it holds throughout the whole range of living organisms, as well as for societies. The relationship between size and complexity is analyzed by examining the effects of size increase and decrease: size increase requires an increase in complexity, whereas size decrease permits, and sometimes requires, a decrease in complexity. Conversely, an increase or decrease in complexity permits, but does not require changes in size. An especially compelling argument for the close relation between size and complexity can be found in size quorum sensing in very small multicellular organisms.}, } @article {pmid15519849, year = {2004}, author = {Sablowski, R}, title = {Plant and animal stem cells: conceptually similar, molecularly distinct?.}, journal = {Trends in cell biology}, volume = {14}, number = {11}, pages = {605-611}, doi = {10.1016/j.tcb.2004.09.011}, pmid = {15519849}, issn = {0962-8924}, support = {BBS/E/J/00000594/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Genetic Variation ; *Plant Development ; Plants/*embryology ; Stem Cells/*physiology ; }, abstract = {Animals and plants maintain small pools of stem cells that continuously provide the precursors of more-specialized cells to sustain growth or to replace tissues. A comparison of plant and animal stem cells can highlight core aspects of stem-cell biology. In both types of organism, stem cells are maintained by intercellular signals that are available only in defined regions (niches) in the tissues. Although plants use different signals and are more flexible at establishing stem-cell niches in new locations, recent evidence suggests that the mechanisms restricting cell fate in stem-cell progeny are similar in both kingdoms and might pre-date the evolution of multicellular organisms.}, } @article {pmid15510168, year = {2004}, author = {Ast, G}, title = {How did alternative splicing evolve?.}, journal = {Nature reviews. Genetics}, volume = {5}, number = {10}, pages = {773-782}, doi = {10.1038/nrg1451}, pmid = {15510168}, issn = {1471-0056}, mesh = {Alternative Splicing/*genetics ; Base Pairing/genetics ; *Evolution, Molecular ; Introns/genetics ; *Models, Genetic ; RNA Splice Sites/*genetics ; RNA, Messenger/*genetics ; }, abstract = {Alternative splicing creates transcriptome diversification, possibly leading to speciation. A large fraction of the protein-coding genes of multicellular organisms are alternatively spliced, although no regulated splicing has been detected in unicellular eukaryotes such as yeasts. A comparative analysis of unicellular and multicellular eukaryotic 5' splice sites has revealed important differences - the plasticity of the 5' splice sites of multicellular eukaryotes means that these sites can be used in both constitutive and alternative splicing, and for the regulation of the inclusion/skipping ratio in alternative splicing. So, alternative splicing might have originated as a result of relaxation of the 5' splice site recognition in organisms that originally could support only constitutive splicing.}, } @article {pmid15500865, year = {2004}, author = {Oswald, RE}, title = {Ionotropic glutamate receptor recognition and activation.}, journal = {Advances in protein chemistry}, volume = {68}, number = {}, pages = {313-349}, doi = {10.1016/S0065-3233(04)68009-0}, pmid = {15500865}, issn = {0065-3233}, mesh = {Animals ; Binding Sites ; Crystallography, X-Ray ; Humans ; Ion Channel Gating/*physiology ; Ligands ; Protein Binding ; Protein Structure, Tertiary ; Receptors, Glutamate/chemistry/*physiology ; Spectrum Analysis ; Structure-Activity Relationship ; }, abstract = {Ionotropic glutamate receptors are the major excitatory neurotransmitters in mammalian brain but are found throughout the animal kingdom as well as in plants and bacteria. A great deal of progress in understanding the structure of these essential neurotransmitter receptors has been made since the first examples were cloned and sequenced in 1989. The atomic structure of the ligand-binding domain of several ionotropic glutamate receptors has been determined, and a great deal of progress has been made in relating the structural properties of the binding site to the function of the intact receptor. In addition, the identification of glutamate receptors from a wide variety of organisms ranging from several types of bacteria to Arabidopsis to a range of animal species has made glutamate receptors a molecular laboratory for studying the evolution of proteins. The fact that glutamate receptors are a particularly ancient intercellular signaling molecule suggests a potential role in the transition from single celled to multicellular organisms. This review focuses on the structure and dynamics of ionotropic glutamate receptors and their relation to the function and evolution of these proteins.}, } @article {pmid15472039, year = {2004}, author = {Nioche, P and Berka, V and Vipond, J and Minton, N and Tsai, AL and Raman, CS}, title = {Femtomolar sensitivity of a NO sensor from Clostridium botulinum.}, journal = {Science (New York, N.Y.)}, volume = {306}, number = {5701}, pages = {1550-1553}, doi = {10.1126/science.1103596}, pmid = {15472039}, issn = {1095-9203}, support = {R01 AI054444/AI/NIAID NIH HHS/United States ; R01 AI054444-05/AI/NIAID NIH HHS/United States ; AY343540//PHS HHS/United States ; }, mesh = {Aerobiosis ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Bacterial Proteins/chemistry/metabolism ; Biological Evolution ; Carrier Proteins/*chemistry/genetics/*metabolism ; Chemotaxis ; Chlamydomonas reinhardtii/chemistry/genetics/metabolism ; Cloning, Molecular ; Clostridium botulinum/*chemistry/genetics/*metabolism ; Crystallography, X-Ray ; Electron Spin Resonance Spectroscopy ; Escherichia coli/genetics/growth & development ; Guanylate Cyclase ; Heme/chemistry/metabolism ; Hemeproteins/*chemistry/genetics/*metabolism ; Humans ; Hydrogen Bonding ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Nitric Oxide/*metabolism ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protoporphyrins/analysis/metabolism ; Receptors, Cytoplasmic and Nuclear/chemistry/metabolism ; Sequence Alignment ; Signal Transduction ; Soluble Guanylyl Cyclase ; Static Electricity ; Thermoanaerobacter/chemistry ; }, abstract = {Nitric oxide (NO) is extremely toxic to Clostridium botulinum, but its molecular targets are unknown. Here, we identify a heme protein sensor (SONO) that displays femtomolar affinity for NO. The crystal structure of the SONO heme domain reveals a previously undescribed fold and a strategically placed tyrosine residue that modulates heme-nitrosyl coordination. Furthermore, the domain architecture of a SONO ortholog cloned from Chlamydomonas reinhardtii indicates that NO signaling through cyclic guanosine monophosphate arose before the origin of multicellular eukaryotes. Our findings have broad implications for understanding bacterial responses to NO, as well as for the activation of mammalian NO-sensitive guanylyl cyclase.}, } @article {pmid15471590, year = {2005}, author = {Garny, A and Noble, D and Kohl, P}, title = {Dimensionality in cardiac modelling.}, journal = {Progress in biophysics and molecular biology}, volume = {87}, number = {1}, pages = {47-66}, doi = {10.1016/j.pbiomolbio.2004.06.006}, pmid = {15471590}, issn = {0079-6107}, support = {G0400145/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Electrophysiology ; Heart/anatomy & histology/*physiology ; Humans ; Ion Channels/physiology ; Mechanoreceptors/physiology ; Models, Anatomic ; *Models, Cardiovascular ; Rabbits ; Sinoatrial Node/anatomy & histology/physiology ; }, abstract = {The development of mathematical models of the heart has been an ongoing concern for many decades. The initial focus of this work was on single cell models that incorporate varyingly detailed descriptions of the mechanisms that give rise to experimentally observed action potential shapes. Clinically relevant heart rhythm disturbances, however, are multicellular phenomena, and there have been many initiatives to develop multidimensional representations of cardiac electromechanical activity. Here, we discuss the merits of dimensionality, from 0D single cell models, to 1D cell strands, 2D planes and 3D volumes, for the simulation of normal and disturbed rhythmicity. We specifically look at models of: (i) the origin and spread of cardiac excitation from the sino-atrial node into atrial tissue, and (ii) stretch-activated channel effects on ventricular cell and tissue activity. Simulation of the spread of normal and disturbed cardiac excitation requires multicellular models. 1D architectures suffer from limitations in neighbouring tissue effects on individual cells, but they can (with some modification) be applied to the simulation of normal spread of excitation or, in ring-like structures, re-entry simulation (colliding wave fronts, tachycardia). 2D models overcome many of the limitations imposed by models of lower dimensionality, and can be applied to the study of complex co-existing re-entry patterns or even fibrillation. 3D implementations are closest to reality, as they allow investigation of scroll waves. Our results suggest that 2D models offer a good compromise between computational resources, complexity of electrophysiological models, and applicability to basic research, and that they should be considered as an important stepping-stone towards anatomically detailed simulations. This highlights the need to identify and use the most appropriate model for any given task. The notion of a single and ultimate model is as useful as the idea of a universal mechanical tool for all possible repairs and servicing requirements in daily life. The ideal model will be as simple as possible and as complex as necessary for the particular question raised.}, } @article {pmid15467096, year = {2004}, author = {Yu, FH and Catterall, WA}, title = {The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis.}, journal = {Science's STKE : signal transduction knowledge environment}, volume = {2004}, number = {253}, pages = {re15}, doi = {10.1126/stke.2532004re15}, pmid = {15467096}, issn = {1525-8882}, mesh = {Animals ; Calcium Signaling/*physiology ; Cations/*metabolism ; Homeostasis/*physiology ; Humans ; Membrane Potentials/physiology ; Models, Biological ; Phylogeny ; Potassium Channels, Calcium-Activated/*physiology ; Potassium Channels, Voltage-Gated/*physiology ; }, abstract = {Complex multicellular organisms require rapid and accurate transmission of information among cells and tissues and tight coordination of distant functions. Electrical signals and resulting intracellular calcium transients, in vertebrates, control contraction of muscle, secretion of hormones, sensation of the environment, processing of information in the brain, and output from the brain to peripheral tissues. In nonexcitable cells, calcium transients signal many key cellular events, including secretion, gene expression, and cell division. In epithelial cells, huge ion fluxes are conducted across tissue boundaries. All of these physiological processes are mediated in part by members of the voltage-gated ion channel protein superfamily. This protein superfamily of 143 members is one of the largest groups of signal transduction proteins, ranking third after the G protein-coupled receptors and the protein kinases in number. Each member of this superfamily contains a similar pore structure, usually covalently attached to regulatory domains that respond to changes in membrane voltage, intracellular signaling molecules, or both. Eight families are included in this protein superfamily-voltage-gated sodium, calcium, and potassium channels; calcium-activated potassium channels; cyclic nucleotide-modulated ion channels; transient receptor potential (TRP) channels; inwardly rectifying potassium channels; and two-pore potassium channels. This article identifies all of the members of this protein superfamily in the human genome, reviews the molecular and evolutionary relations among these ion channels, and describes their functional roles in cell physiology.}, } @article {pmid15465387, year = {2004}, author = {Malagnac, F and Lalucque, H and Lepère, G and Silar, P}, title = {Two NADPH oxidase isoforms are required for sexual reproduction and ascospore germination in the filamentous fungus Podospora anserina.}, journal = {Fungal genetics and biology : FG & B}, volume = {41}, number = {11}, pages = {982-997}, doi = {10.1016/j.fgb.2004.07.008}, pmid = {15465387}, issn = {1087-1845}, mesh = {Amino Acid Sequence ; Base Sequence ; Consensus Sequence ; DNA Primers ; Molecular Sequence Data ; NADPH Oxidases/antagonists & inhibitors/genetics/*metabolism ; Phylogeny ; Podospora/enzymology/genetics/*physiology ; Polymerase Chain Reaction ; Reproduction/physiology ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {NADPH oxidases are enzymes that produce reactive oxygen species (ROS) using electrons derived from intracellular NADPH. In plants and mammals, ROS have been proposed to be second messengers that signal defence responses or cell proliferation. By inactivating PaNox1 and PaNox2, two genes encoding NADPH oxidases, we demonstrate the crucial role of these enzymes in the control of two key steps of the filamentous fungus Podospora anserina life cycle. PaNox1 mutants are impaired in the differentiation of fruiting bodies from their progenitor cells, and the deletion of the PaNox2 gene specifically blocks ascospore germination. Furthermore, we show that PaNox1 likely acts upstream of PaASK1, a MAPKKK previously implicated in stationary phase differentiation and cell degeneration. Using nitro blue tetrazolium (NBT) and diaminobenzidine (DAB) assays, we detect a regulated secretion of both superoxide and peroxide during P. anserina vegetative growth. In addition, two oxidative bursts are shown to occur during fruiting body development and ascospore germination. Analysis of mutants establishes that PaNox1, PaNox2, and PaASK1, as well as a still unknown additional source of ROS, modulate these secretions. Altogether, our data point toward a role for NADPH oxidases in signalling fungal developmental transitions with respect to nutrient availability. These enzymes are conserved in other multicellular eukaryotes, suggesting that early eukaryotes were endowed with a redox network used for signalling purposes.}, } @article {pmid15461797, year = {2004}, author = {Pereira, V}, title = {Insertion bias and purifying selection of retrotransposons in the Arabidopsis thaliana genome.}, journal = {Genome biology}, volume = {5}, number = {10}, pages = {R79}, pmid = {15461797}, issn = {1474-760X}, mesh = {Arabidopsis/*genetics/virology ; *Evolution, Molecular ; Gene Dosage ; *Genome, Plant ; Half-Life ; Mutagenesis, Insertional/*genetics ; Plant Viruses/genetics ; Retroelements/*genetics ; *Selection, Genetic ; Terminal Repeat Sequences/*genetics ; Time Factors ; }, abstract = {BACKGROUND: Genome evolution and size variation in multicellular organisms are profoundly influenced by the activity of retrotransposons. In higher eukaryotes with compact genomes retrotransposons are found in lower copy numbers than in larger genomes, which could be due to either suppression of transposition or to elimination of insertions, and are non-randomly distributed along the chromosomes. The evolutionary mechanisms constraining retrotransposon copy number and chromosomal distribution are still poorly understood.

RESULTS: I investigated the evolutionary dynamics of long terminal repeat (LTR)-retrotransposons in the compact Arabidopsis thaliana genome, using an automated method for obtaining genome-wide, age and physical distribution profiles for different groups of elements, and then comparing the distributions of young and old insertions. Elements of the Pseudoviridae family insert randomly along the chromosomes and have been recently active, but insertions tend to be lost from euchromatic regions where they are less likely to fix, with a half-life estimated at approximately 470,000 years. In contrast, members of the Metaviridae (particularly Athila) preferentially target heterochromatin, and were more active in the past.

CONCLUSION: Diverse evolutionary mechanisms have constrained both the copy number and chromosomal distribution of retrotransposons within a single genome. In A. thaliana, their non-random genomic distribution is due to both selection against insertions in euchromatin and preferential targeting of heterochromatin. Constant turnover of euchromatic insertions and a decline in activity for the elements that target heterochromatin have both limited the contribution of retrotransposon DNA to genome size expansion in A. thaliana.}, } @article {pmid20140231, year = {2004}, author = {Davies, JA}, title = {Inverse Correlation Between an Organ's Cancer Rate and Its Evolutionary Antiquity.}, journal = {Organogenesis}, volume = {1}, number = {2}, pages = {60-63}, pmid = {20140231}, issn = {1547-6278}, abstract = {Human cancer rates vary dramatically across the range of internal organs in the body, but there is no single model to explain the variation and there is also no obvious overall pattern to it. Theories have been proposed to account for high rates in particularly cancer-prone organs, and they usually concentrate on the peculiar vulnerability of certain cells to mutation (e.g., lung cells' direct exposure to airborne carcinogens). These explanations are valuable for understanding mechanisms of disease and also for cancer prevention, but they address neither the overall distribution of cancers nor the possibility that some states of differentiation may be intrinsically less stable than others to the effects of random mutation, a possibility predicted on purely theoretical grounds many years ago. This brief report describes an overall pattern to human organ-specific cancer incidence data and shows that organ-specific cancer rates correlate negatively with an organ's evolutionary antiquity. Although the relationship may just be coincidental, it suggests the possibility that recently-evolved differentiation states may be intricnsically more vulnerable to neoplastic change. Extrapolation of the regression line to a cancer incidence of zero equates to a level of tissue organization typical of 660 Myr ago; the inferred beginning of neoplasia therefore coincides with the rise of complex multicellular animals.}, } @article {pmid15451509, year = {2004}, author = {Bullerwell, CE and Gray, MW}, title = {Evolution of the mitochondrial genome: protist connections to animals, fungi and plants.}, journal = {Current opinion in microbiology}, volume = {7}, number = {5}, pages = {528-534}, doi = {10.1016/j.mib.2004.08.008}, pmid = {15451509}, issn = {1369-5274}, mesh = {Animals ; Chlorophyta/genetics ; DNA, Mitochondrial/chemistry/*genetics ; Eukaryota/classification/*genetics ; *Evolution, Molecular ; Fungi/classification/*genetics ; Gene Order ; Genes ; *Genome ; Mitochondria/*genetics ; Phylogeny ; Plants/classification/*genetics ; }, abstract = {The past decade has seen the determination of complete mitochondrial genome sequences from a taxonomically diverse set of organisms. These data have allowed an unprecedented understanding of the evolution of the mitochondrial genome in terms of gene content and order, as well as genome size and structure. In addition, phylogenetic reconstructions based on mitochondrial DNA (mtDNA)-encoded protein sequences have firmly established the identities of protistan relatives of the animal, fungal and plant lineages. Analysis of the mtDNAs of these protists has provided insight into the structure of the mitochondrial genome at the origin of these three, mainly multicellular, eukaryotic groups. Further research into mtDNAs of taxa ancestral and intermediate to currently characterized organisms will help to refine pathways and modes of mtDNA evolution, as well as provide valuable phylogenetic characters to assist in unraveling the deep branching order of all eukaryotes.}, } @article {pmid15389519, year = {2005}, author = {Montanari, M and Boninsegna, A and Faraglia, B and Coco, C and Giordano, A and Cittadini, A and Sgambato, A}, title = {Increased expression of geminin stimulates the growth of mammary epithelial cells and is a frequent event in human tumors.}, journal = {Journal of cellular physiology}, volume = {202}, number = {1}, pages = {215-222}, doi = {10.1002/jcp.20120}, pmid = {15389519}, issn = {0021-9541}, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism ; Carcinoma/genetics/*metabolism ; Cell Cycle Proteins/genetics/*metabolism ; Cell Line, Transformed ; Cell Line, Tumor ; Cell Proliferation ; Colonic Neoplasms/genetics/metabolism ; DNA Replication/genetics ; DNA, Complementary/genetics ; Epithelial Cells/*metabolism/pathology ; Female ; Geminin ; Gene Expression Regulation, Neoplastic/genetics ; Genes, cdc/physiology ; Humans ; Mammary Glands, Human/*metabolism/pathology/physiopathology ; RNA, Messenger/metabolism ; Rectal Neoplasms/genetics/metabolism ; Transfection ; Up-Regulation/genetics ; }, abstract = {Geminin is a potent inhibitor of origin assembly and re-replication in multicellular eukaryotes and is a negative regulator of DNA replication during the cell cycle. Thus, it was proposed as an inhibitor of cell proliferation and as a potential tumor suppressor gene. However, the protein was found specifically expressed in proliferating lymphocytes and epithelial cells and up-regulated in several malignancies. Therefore, geminin is now regarded as an oncogene but its role in tumor development remains unknown. In this study, we evaluated by Western blot analysis the expression of geminin in a series of human cancer cell lines of various histogenetic origin and in a series of human primary colon, rectal, and breast cancers. Expression of geminin was variable in different cell lines and not related to the expression level of the corresponding mRNA. Moreover, geminin was expressed at higher level in 56% and 58% of colon and rectal cancers, respectively, compared with the corresponding adjacent normal mucosa. A high expression of geminin was also detected by immunohistochemistry in 60% of human primary breast cancers. We also transfected a full-length geminin cDNA in a human non-tumorigenic and a cancer breast cell lines and obtained derivatives expressing high levels of the protein. Geminin overexpression stimulated cell cycle progression and proliferation in both normal and cancer cells and increased the anchorage--independent growth of breast cancer cells. These results demonstrate that expression of geminin is frequently deregulated in tumor cells and might play an important role in the regulation of cell growth in both normal and malignant cells.}, } @article {pmid15366765, year = {2004}, author = {Bowers-Morrow, VM and Ali, SO and Williams, KL}, title = {Comparison of molecular mechanisms mediating cell contact phenomena in model developmental systems: an exploration of universality.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {79}, number = {3}, pages = {611-642}, doi = {10.1017/s1464793103006389}, pmid = {15366765}, issn = {1464-7931}, mesh = {Animals ; *Biological Evolution ; Cadherins/physiology ; Cell Adhesion/*physiology ; Cell Communication/*physiology ; Cell Movement/*physiology ; Models, Biological ; Morphogenesis ; }, abstract = {Are there universal molecular mechanisms associated with cell contact phenomena during metazoan ontogenesis? Comparison of adhesion systems in disparate model systems indicates the existence of unifying principles. Requirements for multicellularity are (a) the construction of three-dimensional structures involving a crucial balance between adhesiveness and motility; and (b) the establishment of integration at molecular, cellular, tissue, and organismal levels of organization. Mechanisms for (i) cell-cell and cell-substrate adhesion, (ii) cell movement, (iii) cell-cell communication, (iv) cellular responses, (v) regulation of these processes, and (vi) their integration with patterning, growth, and other developmental processes are all crucial to metazoan development, and must have been present for the emergence and radiation of Metazoa. The principal unifying themes of this review are the dynamics and regulation of cell contact phenomena. Our knowledge of the dynamic molecular mechanisms underlying cell contact phenomena remains fragmentary. Here we examine the molecular bases of cell contact phenomena using extant model developmental systems (representing a wide range of phyla) including the simplest i.e. sponges, and the eukaryotic protist Dictyostelium discoideum, the more complex Drosophila melanogaster, and vertebrate systems. We discuss cell contact phenomena in a broad developmental context. The molecular language of cell contact phenomena is complex; it involves a plethora of structurally and functionally diverse molecules, and diverse modes of intermolecular interactions mediated by protein and/or carbohydrate moieties. Reasons for this are presumably the necessity for a high degree of specificity of intermolecular interactions, the requirement for a multitude of different signals, and the apparent requirement for an increasingly large repertoire of cell contact molecules in more complex developmental systems, such as the developing vertebrate nervous system. However, comparison of molecular models for dynamic adhesion in sponges and in vertebrates indicates that, in spite of significant differences in the details of the way specific cell-cell adhesion is mediated, similar principles are involved in the mechanisms employed by members of disparate phyla. Universal requirements are likely to include (a) rapidly reversible intermolecular interactions; (b) low-affinity intermolecular interactions with fast on-off rates; (c) the compounding of multiple intermolecular interactions; (d) associated regulatory signalling systems. The apparent widespread employment of molecular mechanisms involving cadherin-like cell adhesion molecules suggests the fundamental importance of cadherin function during development, particularly in epithelial morphogenesis, cell sorting, and segregation of cells.}, } @article {pmid15366763, year = {2004}, author = {Knell, RJ and Webberley, KM}, title = {Sexually transmitted diseases of insects: distribution, evolution, ecology and host behaviour.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {79}, number = {3}, pages = {557-581}, doi = {10.1017/s1464793103006365}, pmid = {15366763}, issn = {1464-7931}, mesh = {Animals ; *Biological Evolution ; *Ecology ; Female ; Host-Parasite Interactions/physiology ; Insect Vectors ; *Insecta/microbiology/parasitology/virology ; Male ; Population Dynamics ; Reproduction ; Sexual Behavior, Animal ; }, abstract = {Sexually transmitted diseases (STDs) of insects are known from the mites, nematodes, fungi, protists and viruses. In total 73 species of parasite and pathogen from approximately 182 species of host have been reported. Whereas nearly all vertebrate STDs are viruses or bacteria, the majority of insect STDs are multicellular ectoparasites, protistans or fungi. Insect STDs display a range of transmission modes, with 'pure' sexual transmission only described from ectoparasites, all of which are mites, fungi or nematodes, whereas the microparasitic endo-parasites tend to show vertical as well as sexual transmission. The distribution of STDs within taxa of insect hosts appears to be related to the life histories of the hosts. In particular, STDs will not be able to persist if host adult generations do not overlap unless they are also transmitted by some alternative route. This explains the observation that the Coleoptera seem to suffer from more STDs than other insect orders, since they tend to diapause as adults and are therefore more likely to have overlapping generations of adults in temperate regions. STDs of insects are often highly pathogenic, and are frequently responsible for sterilizing their hosts, a feature which is also found in mammalian STDs. This, combined with high prevalences indicates that STDs can be important in the evolution and ecology of their hosts. Although attempts to demonstrate mate choice for uninfected partners have so far failed it is likely that STDs have other effects on host mating behaviour, and there is evidence from a few systems that they might manipulate their hosts to cause them to mate more frequently. STDs may also play a part in sexual conflict, with males in some systems possibly gaining a selective advantage from transmitting certain STDs to females. STDs may well be important factors in host population dynamics, and some have the potential to be useful biological control agents, but empirical studies on these subjects are lacking.}, } @article {pmid15363926, year = {2004}, author = {Keränen, SV}, title = {Simulation study on effects of signaling network structure on the developmental increase in complexity.}, journal = {Journal of theoretical biology}, volume = {231}, number = {1}, pages = {3-21}, doi = {10.1016/j.jtbi.2004.03.021}, pmid = {15363926}, issn = {0022-5193}, support = {R01 GM42387/GM/NIGMS NIH HHS/United States ; R01 GM70444/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Cell Physiological Phenomena ; *Computer Simulation ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; *Models, Genetic ; Morphogenesis/genetics ; Signal Transduction/*physiology ; }, abstract = {The developmental increase in structural complexity in multicellular lifeforms depends on local, often non-periodic differences in gene expression. These, in turn, depend on a network of gene-gene interactions coded within the organismal genome. To see what architectural features of a network (size, connectivity, etc.) affect the likelihood of patterns with multiple cell types (i.e. patterns where cells express > or = 3 different combinations of genes), developmental pattern formation was simulated in virtual blastoderm embryos with small artificial genomes. Several basic properties of these genomic signaling networks, such as the number of genes, the distributions of positive (inductive) and negative (repressive) interactions, and the strengths of gene-gene interactions were tested. The results show that the frequencies of complex and/or stable patterns depended not only on the existence of negative interactions, but also on the distribution of regulatory interactions: for example, coregulation of signals and their intracellular effectors increased the likelihood of pattern formation compared to differential regulation of signaling pathway components. Interestingly, neither quantitative differences in strengths of signaling interactions nor multiple response thresholds to different levels of signal concentration (as in morphogen gradients) were essential for formation of multiple, spatially unique "cell types". However, those combinations of architectural features that greatly increased the likelihood for pattern complexity tended to decrease the likelihoods for pattern stability and developmental robustness. Nevertheless, elements of complex patterns (e.g. genes, cell type order within the pattern) could differ in their developmental robustness, which may be important for the evolution of complexity. The results show that depending on the network structure, the same set of genes can produce patterns of different complexity, robustness and stability. Because of this, the evolution of metazoan complexity with a combinatorial code of gene regulation may have depended at least as much on selection for favorable distribution of connections between existing developmental regulatory genes as on the simple increase in numbers of regulatory genes.}, } @article {pmid15363407, year = {2004}, author = {King, N}, title = {The unicellular ancestry of animal development.}, journal = {Developmental cell}, volume = {7}, number = {3}, pages = {313-325}, doi = {10.1016/j.devcel.2004.08.010}, pmid = {15363407}, issn = {1534-5807}, mesh = {Animals ; *Biological Evolution ; DNA, Mitochondrial/metabolism ; Environment ; Eukaryota ; Evolution, Molecular ; Gene Expression Regulation ; Genome ; Models, Biological ; Phylogeny ; Porifera/metabolism ; Signal Transduction ; Tissue Adhesions ; Transcription, Genetic ; }, abstract = {The transition to multicellularity that launched the evolution of animals from protozoa marks one of the most pivotal, and poorly understood, events in life's history. Advances in phylogenetics and comparative genomics, and particularly the study of choanoflagellates, are yielding new insights into the biology of the unicellular progenitors of animals. Signaling and adhesion gene families critical for animal development (including receptor tyrosine kinases and cadherins) evolved in protozoa before the origin of animals. Innovations in transcriptional regulation and expansions of certain gene families may have allowed the integration of cell behavior during the earliest experiments with multicellularity. The protozoan perspective on animal origins promises to provide a valuable window into the distant past and into the cellular bases of animal development.}, } @article {pmid15358765, year = {2004}, author = {Aouacheria, A and Cluzel, C and Lethias, C and Gouy, M and Garrone, R and Exposito, JY}, title = {Invertebrate data predict an early emergence of vertebrate fibrillar collagen clades and an anti-incest model.}, journal = {The Journal of biological chemistry}, volume = {279}, number = {46}, pages = {47711-47719}, doi = {10.1074/jbc.M408950200}, pmid = {15358765}, issn = {0021-9258}, mesh = {Amino Acid Sequence ; Animals ; Anopheles/chemistry/genetics ; Ciona intestinalis/chemistry/genetics ; *Evolution, Molecular ; Exons ; Fibrillar Collagens/chemistry/*classification/*genetics ; Gene Duplication ; Humans ; Introns ; Invertebrates/chemistry/*genetics ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; Vertebrates/*genetics/metabolism ; }, abstract = {Fibrillar collagens are involved in the formation of striated fibrils and are present from the first multicellular animals, sponges, to humans. Recently, a new evolutionary model for fibrillar collagens has been suggested (Boot-Handford, R. P., Tuckwell, D. S., Plumb, D. A., Farrington Rock, C., and Poulsom, R. (2003) J. Biol. Chem. 278, 31067-31077). In this model, a rare genomic event leads to the formation of the founder vertebrate fibrillar collagen gene prior to the early vertebrate genome duplications and the radiation of the vertebrate fibrillar collagen clades (A, B, and C). Here, we present the modular structure of the fibrillar collagen chains present in different invertebrates from the protostome Anopheles gambiae to the chordate Ciona intestinalis. From their modular structure and the use of a triple helix instead of C-propeptide sequences in phylogenetic analyses, we were able to show that the divergence of A and B clades arose early during evolution because alpha chains related to these clades are present in protostomes. Moreover, the event leading to the divergence of B and C clades from a founder gene arose before the appearance of vertebrates; altogether these data contradict the Boot-Handford model. Moreover, they indicate that all the key steps required for the formation of fibrils of variable structure and functionality arose step by step during invertebrate evolution.}, } @article {pmid15358580, year = {2004}, author = {Tye, BK and Chang, VK}, title = {Dual functional regulators coordinate DNA replication and gene expression in proliferating cells.}, journal = {Frontiers in bioscience : a journal and virtual library}, volume = {9}, number = {}, pages = {2548-2555}, doi = {10.2741/1416}, pmid = {15358580}, issn = {1093-9946}, support = {GM34190/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antigens, Polyomavirus Transforming/metabolism ; Bacterial Proteins/metabolism ; Cell Cycle Proteins/metabolism ; Cell Differentiation ; Cell Proliferation ; *DNA Replication ; DNA-Binding Proteins/metabolism ; E2F Transcription Factors/metabolism ; Escherichia coli/metabolism ; *Gene Expression Regulation ; *Gene Expression Regulation, Bacterial ; Minichromosome Maintenance 1 Protein/metabolism ; Minichromosome Maintenance Complex Component 7 ; Nuclear Proteins/metabolism ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; }, abstract = {Gene products for cell growth must meet the pace of DNA replication and vice versa during the cell division cycle, therefore coordination of DNA replication and gene expression is vital to proliferating cells. During development in multicellular organisms when rapid cell divisions must be accompanied by the expression of particular gene sets in differentiating tissues, this coordination is even more crucial. Undoubtedly, multiple strategies are used to ensure the coordination of gene expression and DNA replication. In this review, we focus on the strategy that uses dual functional factors to serve both the functions of replication initiator and transcription regulator. Classical examples are the dual functional replication initiator/transcription regulators, DnaA of E. coli and T antigen of SV40, which bind replication origins and regulate their own synthesis. Emerging examples in eukaryotes are the growth responsive transcription factor E2f, the MADS domain combinatorial transcription factor Mcm1, and a subunit of the MCM2-7 helicase, Mcm7.}, } @article {pmid15355246, year = {2005}, author = {Hughes, KA and Reynolds, RM}, title = {Evolutionary and mechanistic theories of aging.}, journal = {Annual review of entomology}, volume = {50}, number = {}, pages = {421-445}, doi = {10.1146/annurev.ento.50.071803.130409}, pmid = {15355246}, issn = {0066-4170}, mesh = {Aging/*physiology ; Animals ; *Biological Evolution ; Caenorhabditis elegans/physiology ; Drosophila melanogaster/physiology ; Food Deprivation ; Humans ; Oxidative Stress ; Population Dynamics ; Signal Transduction ; }, abstract = {Senescence (aging) is defined as a decline in performance and fitness with advancing age. Senescence is a nearly universal feature of multicellular organisms, and understanding why it occurs is a long-standing problem in biology. Here we present a concise review of both evolutionary and mechanistic theories of aging. We describe the development of the general evolutionary theory, along with the mutation accumulation, antagonistic pleiotropy, and disposable soma versions of the evolutionary model. The review of the mechanistic theories focuses on the oxidative stress resistance, cellular signaling, and dietary control mechanisms of life span extension. We close with a discussion of how an approach that makes use of both evolutionary and molecular analyses can address a critical question: Which of the mechanisms that can cause variation in aging actually do cause variation in natural populations?}, } @article {pmid15353909, year = {2004}, author = {Fritzsch, B and Beisel, KW}, title = {Keeping sensory cells and evolving neurons to connect them to the brain: molecular conservation and novelties in vertebrate ear development.}, journal = {Brain, behavior and evolution}, volume = {64}, number = {3}, pages = {182-197}, pmid = {15353909}, issn = {0006-8977}, support = {R01 DC005009/DC/NIDCD NIH HHS/United States ; R01 DC04279/DC/NIDCD NIH HHS/United States ; R01 DC004279/DC/NIDCD NIH HHS/United States ; R01 DC005590/DC/NIDCD NIH HHS/United States ; R01 DC05009/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Ear/growth & development/innervation/*physiology ; Evolution, Molecular ; Eye/growth & development ; Humans ; Mechanoreceptors/growth & development/*physiology ; Neural Pathways/cytology/*physiology ; Neurons, Afferent/*physiology ; Species Specificity ; Vertebrates/*anatomy & histology/physiology ; }, abstract = {The evolution of the mechanosensory cellular module and the molecular details that regulate its development has included morphological modifications of these cells as well as the formation of larger assemblies of mechanosensory cell aggregates among metazoans. This has resulted in a wide diversity of mechanosensory organs. The wide morphological diversity of organs, including the associated morphological modifications of the mechanosensory cells, suggests parallel evolution of these modules and their associated organs. This morphological diversity is in stark contrast to the molecular conservation of developmental modules across phyla. These molecular data suggest that the evolution of mechanosensory transduction might have preceded that of distinct cellular differentiation. However, once a molecular network governing development of specialized cells involved in mechanosensory transduction evolved, that molecular network was preserved across phyla. Present data suggest that at least the common ancestor of triploblastic organisms, perhaps even the common diploblastic ancestor of bilaterian metazoans, had molecular and cellular specializations for mechanosensation. It is argued that the evolution of multicellular organs dedicated to specific aspects of mechanosensation, such as gravity and sound perception, are evolutionary transformations that build on this conserved molecular network for cellular specialization, but reflect distinct morphological solutions. We propose that the sensory neurons, connecting the craniate ear with the brain, are a derived feature of craniates, and possibly chordates, that came about through diversification of the lineage forming mechanosensory cells during development. This evolutionarily late event suggests a heterochronic shift, so that sensory neurons develop in mammals prior to mechanosensory hair cells. However, sensory neuron development is connected to hair cell development, likely in a clonal relationship. The theme of cellular conservation is reiterated in two examples of chordate otic diversification: the evolution of the horizontal canal system and the evolution of the basilar papilla/cochlea. It is suggested that here again, cellular multiplication and formation of a special epithelium predates the functional transformation to an 'organ' system for horizontal angular acceleration and sound pressure reception, respectively. Overall, evolution of the vertebrate ear needs to be understood as an interplay between and utilization of two gene networks or modules. One is at the level of the molecularly and developmentally conserved mechanosensory cellular module. The other is an increased complexity in the morphology of both adult mechanosensory cells and organs by the addition of end-stage and novel features and associated gene networks to detect specific aspects of mechanosensory stimuli.}, } @article {pmid15353355, year = {2004}, author = {Sakharkar, MK and Chow, VT and Chaturvedi, I and Mathura, VS and Shapshak, P and Kangueane, P}, title = {A report on single exon genes (SEG) in eukaryotes.}, journal = {Frontiers in bioscience : a journal and virtual library}, volume = {9}, number = {}, pages = {3262-3267}, doi = {10.2741/1478}, pmid = {15353355}, issn = {1093-9946}, support = {DA014533/DA/NIDA NIH HHS/United States ; GM056529/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biodiversity ; Databases, Genetic ; Eukaryotic Cells/metabolism ; Evolution, Molecular ; *Exons ; Genome ; Genomics/*methods ; Humans ; *Models, Genetic ; Species Specificity ; }, abstract = {Single exon genes (SEG) are archetypical of prokaryotes. Hence, their presence in intron-rich, multi-cellular eukaryotic genomes is perplexing. Consequently, a study on SEG origin and evolution is important. Towards this goal, we took the first initiative of identifying and counting SEG in nine completely sequenced eukaryotic organisms--four of which are unicellular (E. cuniculi, S. cerevisiae, S. pombe, P. falciparum) and five of which are multi-cellular (C. elegans, A. thaliana, D. melanogaster, M. musculus, H. sapiens). This exercise enabled us to compare their proportion in unicellular and multi-cellular genomes. The comparison suggests that the SEG fraction decreases with gene count (r = -0.80) and increases with gene density (r = 0.88) in these genomes. We also examined the distribution patterns of their protein lengths in different genomes.}, } @article {pmid15351140, year = {2004}, author = {Ardelean, I and Gheorghe, M and Martín-Vide, C and Mitrana, V}, title = {A computational model for cell differentiation.}, journal = {Bio Systems}, volume = {76}, number = {1-3}, pages = {169-176}, doi = {10.1016/j.biosystems.2004.05.009}, pmid = {15351140}, issn = {0303-2647}, mesh = {*Algorithms ; Animals ; *Artificial Intelligence ; *Biological Evolution ; Cell Differentiation/*physiology ; Cell Division/*physiology ; Cell Proliferation ; Computer Simulation ; Feedback/*physiology ; Humans ; *Models, Biological ; }, abstract = {In this paper, we present a word set generating mechanism, called cell-differentiation system, inspired by the tissue process formation in multicellular organisms, which might model some properties of evolving communities of living cells at the syntactical level. The tools utilized to model these biological phenomena belong to the formal language theory. In this context chromosomal mutations are defined as operations on strings and the differentiation according to the control of gene expression is represented by some random-context conditions in formal languages. In the presented formal framework we prove that in a simplified form of this formalism, with only one cell-type which is regular, one single cell and no mitosis involved, the problem of establishing whether or not the set of vectors of integers indicating the number of cells in each population, is finite, linear or semilinear, is recursively undecidable. However, one can algorithmically decide whether or not a cell-differentiation system of finite cell-type can produce a specific generation of cells.}, } @article {pmid15340379, year = {2004}, author = {Lucas, WJ and Lee, JY}, title = {Plasmodesmata as a supracellular control network in plants.}, journal = {Nature reviews. Molecular cell biology}, volume = {5}, number = {9}, pages = {712-726}, doi = {10.1038/nrm1470}, pmid = {15340379}, issn = {1471-0072}, mesh = {Cell Communication/*physiology ; Green Fluorescent Proteins ; Luminescent Proteins/metabolism ; Models, Biological ; Plant Development ; Plant Diseases ; *Plant Physiological Phenomena ; Plant Proteins/*metabolism ; Plants/anatomy & histology ; Plasmodesmata/*metabolism ; Protein Transport ; RNA, Plant/metabolism ; }, abstract = {The evolution of intercellular communication had an important role in the increasing complexity of both multicellular and supracellular organisms. Plasmodesmata, the intercellular organelles of the plant kingdom, establish an effective pathway for local and long-distance signalling. In higher plants, this pathway involves the trafficking of proteins and various forms of RNA that function non-cell-autonomously to affect developmental programmes.}, } @article {pmid15331635, year = {2004}, author = {Okai, T and Araki, Y and Tada, M and Tateno, T and Kontani, K and Katada, T}, title = {Novel small GTPase subfamily capable of associating with tubulin is required for chromosome segregation.}, journal = {Journal of cell science}, volume = {117}, number = {Pt 20}, pages = {4705-4715}, doi = {10.1242/jcs.01347}, pmid = {15331635}, issn = {0021-9533}, mesh = {ADP-Ribosylation Factors/classification/genetics/*metabolism ; Amino Acid Sequence ; Animals ; Cell Cycle/physiology ; Cell Line ; Chromosome Aberrations ; *Chromosome Segregation ; Drosophila melanogaster ; GTP Phosphohydrolases/classification/genetics/*metabolism ; Humans ; Microtubule-Associated Proteins/classification/genetics/*metabolism ; Microtubules/metabolism ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Protein Isoforms/classification/genetics/*metabolism ; RNA Interference ; Sequence Alignment ; Tissue Distribution ; Tubulin/*metabolism ; }, abstract = {The small GTPase superfamily, which includes the Ras, Rho/Rac, Rab, Arf and Ran subfamilies, serves as a signal transducer to regulate cell proliferation and differentiation, actin cytoskeleton, membrane trafficking, and nuclear transport. Here, we identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases in terms of their sequences and intracellular function. Gie stands for 'novel GTPase indispensable for equal segregation of chromosomes', and this subfamily is conserved in multicellular organisms. Expression of dominant-negative Gie mutants in mammalian cells or knockdown of Gie transcripts using RNA interference in Drosophila S2 cells induced abnormal morphology in the chromosome segregation. Gie protein has ability to bind to tubulin and localizes with microtubules on the spindle mid-zone in late mitosis. Furthermore, overexpression of Gie mutants that lack putative effector domains but have tubulin-binding ability induced micronucleus formation. Thus, this is the first report showing that a small GTPase subfamily capable of associating with microtubules might be involved in chromosome segregation.}, } @article {pmid15308755, year = {2004}, author = {Ramirez-Parra, E and López-Matas, MA and Fründt, C and Gutierrez, C}, title = {Role of an atypical E2F transcription factor in the control of Arabidopsis cell growth and differentiation.}, journal = {The Plant cell}, volume = {16}, number = {9}, pages = {2350-2363}, pmid = {15308755}, issn = {1040-4651}, mesh = {Arabidopsis/genetics/*growth & development/*metabolism ; Arabidopsis Proteins/*genetics/isolation & purification/*metabolism ; Cell Cycle Proteins/genetics/isolation & purification/*metabolism ; Cell Differentiation/*genetics ; Cell Division/genetics ; Cell Wall/genetics/metabolism ; DNA, Complementary/analysis/genetics ; DNA-Binding Proteins/*genetics/isolation & purification/*metabolism ; E2F Transcription Factors ; Gene Expression Regulation, Plant/*genetics ; Genes, cdc ; Growth Inhibitors/metabolism ; Hypocotyl/genetics/growth & development/metabolism ; Molecular Sequence Data ; Mutation/genetics ; Phylogeny ; Plant Roots/genetics/growth & development/metabolism ; Ploidies ; Promoter Regions, Genetic/genetics ; RNA, Messenger/metabolism ; Repressor Proteins/*genetics/metabolism ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Transcription Factors/genetics/isolation & purification/*metabolism ; }, abstract = {The balance between cell proliferation and differentiation is crucial in multicellular organisms, where it is regulated by complex gene expression networks. This is particularly relevant in plants because organogenesis is a continuous postembryonic process. Here, we investigate the function of Arabidopsis thaliana E2Ff, an atypical member of the E2F family of transcription factors, which acts independently of a dimerization partner. We have focused our analysis on roots and hypocotyls, organs where (1) cell proliferation and differentiation are spatially and/or temporally separated, (2) growth depends on cell expansion in the longitudinal axis, and (3) the AtE2Ff promoter is active. AtE2Ff overexpression produced a reduction in the size of differentiated cells of these organs. Cells of mutant e2ff-1 plants with reduced levels of AtE2Ff mRNA were larger, especially in the hypocotyl, suggesting a role as a growth regulator. These effects of AtE2Ff are not associated with changes in nuclear ploidy levels or in the expression of cell cycle marker genes. However, expression of a subset of cell wall biogenesis genes is misregulated in an AtE2Ff-dependent manner, and based on chromatin immunoprecipitation experiments, they seem to be direct E2F targets. Our results highlight the complex regulatory function exerted by E2F and suggest a possible role of AtE2Ff in repressing cell wall biosynthesis genes during cell elongation in differentiated cells.}, } @article {pmid15285787, year = {2004}, author = {Zelensky, AN and Gready, JE}, title = {C-type lectin-like domains in Fugu rubripes.}, journal = {BMC genomics}, volume = {5}, number = {1}, pages = {51}, pmid = {15285787}, issn = {1471-2164}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Evolution, Molecular ; Fishes/genetics ; Gene Duplication ; Genes ; Humans ; Lectins, C-Type/chemistry/*genetics ; Mammals/genetics ; Molecular Sequence Data ; *Multigene Family ; Phylogeny ; Protein Structure, Tertiary ; Sequence Alignment ; Sequence Homology, Amino Acid ; Species Specificity ; Takifugu/*genetics ; }, abstract = {BACKGROUND: Members of the C-type lectin domain (CTLD) superfamily are metazoan proteins functionally important in glycoprotein metabolism, mechanisms of multicellular integration and immunity. Three genome-level studies on human, C. elegans and D. melanogaster reported previously demonstrated almost complete divergence among invertebrate and mammalian families of CTLD-containing proteins (CTLDcps).

RESULTS: We have performed an analysis of CTLD family composition in Fugu rubripes using the draft genome sequence. The results show that all but two groups of CTLDcps identified in mammals are also found in fish, and that most of the groups have the same members as in mammals. We failed to detect representatives for CTLD groups V (NK cell receptors) and VII (lithostathine), while the DC-SIGN subgroup of group II is overrepresented in Fugu. Several new CTLD-containing genes, highly conserved between Fugu and human, were discovered using the Fugu genome sequence as a reference, including a CSPG family member and an SCP-domain-containing soluble protein. A distinct group of soluble dual-CTLD proteins has been identified, which may be the first reported CTLDcp group shared by invertebrates and vertebrates. We show that CTLDcp-encoding genes are selectively duplicated in Fugu, in a manner that suggests an ancient large-scale duplication event. We have verified 32 gene structures and predicted 63 new ones, and make our annotations available through a distributed annotation system (DAS) server http://anz.anu.edu.au:8080/Fugu_rubripes/ and their sequences as additional files with this paper.

CONCLUSIONS: The vertebrate CTLDcp family was essentially formed early in vertebrate evolution and is completely different from the invertebrate families. Comparison of fish and mammalian genomes revealed three groups of CTLDcps and several new members of the known groups, which are highly conserved between fish and mammals, but were not identified in the study using only mammalian genomes. Despite limitations of the draft sequence, the Fugu rubripes genome is a powerful instrument for gene discovery and vertebrate evolutionary analysis. The composition of the CTLDcp superfamily in fish and mammals suggests that large-scale duplication events played an important role in the evolution of vertebrates.}, } @article {pmid15280020, year = {2004}, author = {Zeng, LC and Liu, F and Zhang, X and Zhu, ZD and Wang, ZQ and Han, ZG and Ma, WJ}, title = {hOLF44, a secreted glycoprotein with distinct expression pattern, belongs to an uncharacterized olfactomedin-like subfamily newly identified by phylogenetic analysis.}, journal = {FEBS letters}, volume = {571}, number = {1-3}, pages = {74-80}, doi = {10.1016/j.febslet.2004.06.059}, pmid = {15280020}, issn = {0014-5793}, mesh = {Amino Acid Sequence ; Animals ; Chickens ; Cloning, Molecular ; Conserved Sequence ; Embryo, Mammalian/physiology ; Embryo, Nonmammalian ; Extracellular Matrix Proteins/*classification/genetics ; Female ; Glycoproteins/*classification/*genetics ; Humans ; Molecular Sequence Data ; *Phylogeny ; Placenta/physiology ; Pregnancy ; Protein Biosynthesis/genetics ; Recombinant Proteins/chemistry/classification ; Sequence Alignment ; Sequence Homology, Amino Acid ; Transcription, Genetic/genetics ; Transfection ; }, abstract = {Secreted proteins are indispensable for the development and differentiation of multicellular organisms. Cloning and characterization of novel or hypothetical genes encoding these proteins are therefore inviting great incentives. Using bioinformatics tools and experimental approaches, we isolated and characterized a human secreted glycoprotein, hOLF44, which contains a highly conserved olfactomedin-like (OLF) domain in the C-terminal. However, phylogenetic analysis revealed that hOLF44 is not clustered into any of the OLF subfamilies containing characterized members, and obviously falls into a newly identified uncharacterized OLF subfamily. Western blot analysis showed that hOLF44 protein is robustly secreted from the transfected COS-7 cells. Expression levels of hOLF44 mRNA are abundant in placenta, moderate in liver and heart, whereas fairly weak in other tissues examined. Immunohistochemical study on human term placenta demonstrated that hOLF44 is mainly localized extracellularly surrounding the syncytiotrophoblastic cells and very rarely expressed in the maternal decidua layer. These results suggest that hOLF44 may have matrix-related function involved in human placental and embryonic development, or play a similar role in other physiological processes. The further functional characterization of hOLF44 may provide insights into a better understanding of the newly identified OLF subfamily.}, } @article {pmid15262788, year = {2004}, author = {Dieterich, C and Rahmann, S and Vingron, M}, title = {Functional inference from non-random distributions of conserved predicted transcription factor binding sites.}, journal = {Bioinformatics (Oxford, England)}, volume = {20 Suppl 1}, number = {}, pages = {i109-15}, doi = {10.1093/bioinformatics/bth908}, pmid = {15262788}, issn = {1367-4811}, mesh = {Animals ; Binding Sites ; Computer Simulation ; Conserved Sequence/*genetics ; *Evolution, Molecular ; HeLa Cells ; Humans ; Mice ; *Models, Genetic ; Models, Statistical ; Protein Binding ; Regulatory Sequences, Nucleic Acid/*genetics ; Sequence Analysis, DNA/*methods ; Statistical Distributions ; Transcription Factors/*genetics ; }, abstract = {MOTIVATION: Our understanding of how genes are regulated in a concerted fashion is still limited. Especially, complex phenomena like cell cycle regulation in multicellular organisms are poorly understood. Therefore, we investigated conserved predicted transcription factor binding sites (TFBSs) in man-mouse upstream regions of genes that can be associated to a particular cell cycle phase in HeLa cells. TFBSs were predicted from selected binding site motifs (represented by position weight matrices, PWMs) based on a statistical approach. A regulatory role for a transcription factor is more probable if its predicted TFBSs are enriched in upstream regions of genes, that are associated with a subset of cell cycle phases. We tested for this association by computing exact P-values for the observed phase distributions under the null distribution defined by the relative amount of conserved upstream sequence of genes per cell cycle phase. We considered non-exonic and 5'-untranslated region (5'-UTR) binding sites separately and corrected for multiple testing by taking the false discovery rate into account.

RESULTS: We identified 22 non-exonic and 11 5'-UTR significant PWM phase distributions although expecting one false discovery. Many of the corresponding transcription factors (e.g. members of the thyroid hormone/retinoid receptor subfamily) have already been associated with cell cycle regulation, proliferation and development. It appears that our method is a suitable tool for detecting putative cell cycle regulators in the realm of known human transcription factors.

AVAILABILITY: Further details and supplementary data can be obtained from http://corg.molgen.mpg.de/cellcycle}, } @article {pmid15261667, year = {2004}, author = {de Graffenried, CL and Bertozzi, CR}, title = {The roles of enzyme localisation and complex formation in glycan assembly within the Golgi apparatus.}, journal = {Current opinion in cell biology}, volume = {16}, number = {4}, pages = {356-363}, doi = {10.1016/j.ceb.2004.06.007}, pmid = {15261667}, issn = {0955-0674}, support = {GM59907/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Gangliosides/biosynthesis ; Glycosylation ; Glycosyltransferases/*metabolism ; Golgi Apparatus/*enzymology ; Heparitin Sulfate/biosynthesis ; Humans ; Mannosidases/chemistry/metabolism ; Models, Biological ; Polysaccharides/*metabolism ; Protein Transport ; }, abstract = {Cell surface glycans govern numerous cell-cell interactions are therefore key determinants of multicellular biology. They originate from biosynthetic pathways comprising an assembly line of glycosyltransferases within the Golgi compartment. Although the mechanisms of Golgi enzyme localisation are still under debate, the distribution of these enzymes among the Golgi cisternae can dictate the overall structures produced by the cell. Fine-tuning of glycan biosynthetic pathways is further accomplished by specific associations among glycosyltransferases. Together, localisation and association govern the assembly of complex glycans and thereby regulate interactions at the cell surface.}, } @article {pmid15256603, year = {2004}, author = {Werfel, J and Bar-Yam, Y}, title = {The evolution of reproductive restraint through social communication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {101}, number = {30}, pages = {11019-11024}, pmid = {15256603}, issn = {0027-8424}, support = {T32 GM007484/GM/NIGMS NIH HHS/United States ; GM07484/GM/NIGMS NIH HHS/United States ; }, mesh = {Altruism ; Communication ; Humans ; Models, Biological ; Reproduction/*physiology ; Sexual Behavior/*physiology ; *Social Behavior ; Stochastic Processes ; }, abstract = {The evolution of altruistic behavior through group selection is generally viewed as possible in theory but unlikely in reality, because individual selection favoring selfish strategies should act more rapidly than group selection favoring cooperation. Here we demonstrate the evolution of altruism, in the form of conditional reproductive restraint based on an explicitly social mechanism, modulated by intrapopulation communication comprising signal and evolved response, in a spatially distributed predatory/parasitic/pathogenic model system. The predatory species consistently comes to exploit a signal implying overcrowding, individuals constraining their reproduction in response, with a corresponding increase in equilibrium reproduction rate in the absence of signal. This signaled restraint arises in a robust way for a range of model spatial systems; it outcompetes non-signal-based restraint and is not vulnerable to subversion by noncooperating variants. In these systems, communication is used to evaluate population density and regulate reproduction accordingly, consistent with central ideas of Wynne-Edwards [Wynne-Edwards, V. C. (1962) Animal Dispersion in Relation to Social Behavior (Hafner, New York)], whose claims about the evolutionary importance of group selection helped ignite decades of controversy. This quantitative simulation model shows how the key evolutionary transition from solitary living to sociality can occur. The process described here of cooperation evolving through communication may also help to explain other major evolutionary transitions such as intercellular communication leading to multicellular organisms.}, } @article {pmid15256266, year = {2004}, author = {Ellington, WR and Yamashita, D and Suzuki, T}, title = {Alternative splicing produces transcripts coding for alpha and beta chains of a hetero-dimeric phosphagen kinase.}, journal = {Gene}, volume = {334}, number = {}, pages = {167-174}, doi = {10.1016/j.gene.2004.03.031}, pmid = {15256266}, issn = {0378-1119}, mesh = {*Alternative Splicing ; Animals ; Base Sequence ; DNA/chemistry/genetics ; DNA, Complementary/chemistry/genetics ; Dimerization ; Escherichia coli/genetics ; Gene Expression Regulation, Enzymologic ; Isoenzymes/chemistry/genetics/isolation & purification ; Molecular Sequence Data ; Phosphotransferases (Nitrogenous Group Acceptor)/chemistry/*genetics/isolation & purification ; Polychaeta/enzymology/*genetics ; Protein Subunits/chemistry/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Transcription, Genetic/genetics ; }, abstract = {Glycocyamine kinase (GK) catalyzes the reversible phosphorylation of glycocyamine (guanidinoacetate), a reaction central to cellular energy homeostasis in certain animals. GK is a member of the phosphagen kinase enzyme family and appears to have evolved from creatine kinase (CK) early in the evolution of multi-cellular animals. Prior work has shown that GK from the polychaete Neanthes (Nereis) diversicolor exits as a hetero-dimer in vivo and that the two polypeptide chains (termed alpha and beta) are coded for by unique transcripts. In the present study, we demonstrate that the GK from a congener Nereis virens is also hetero-dimeric and is coded for by alpha and beta transcripts, which are virtually identical to the corresponding forms in N. diversicolor. The GK gene from N. diversicolor was amplified by PCR. Sequencing of the PCR products showed that the alpha and beta chains are the result of alternative splicing of the GK primary mRNA transcript. These results also strongly suggest that this gene underwent an early tandem exon duplication event. Full-length cDNAs for N. virens GKalpha and GKbeta were individually ligated into expression vectors and the resulting constructs used to transform Escherichia coli expression hosts. Regardless of expression conditions, minimal GK activity was observed in both GKalpha and GKbeta constructs. Inclusion bodies for both were harvested, unfolded in urea and alpha chains, beta chains and mixtures of alpha and beta chains were refolded by sequential dialysis. Only modest amounts of GK activity were observed when alpha and beta were refolded individually. In contrast, when refolded the alpha and beta mixture yielded highly active hetero-dimers, as validated by size exclusion chromatography, electrophoresis and mass spectrometry, with a specific activity comparable to that of natural GK. The above evidence suggests that there is a preference for hetero-dimer formation in the GKs from these two polychaetes. The evolution of the alternate splicing and an additional exon in these GKs, producing alpha and beta transcripts, can be viewed as a possible compensation for a mutation(s) in the original gene, which most likely coded for a homo-dimeric protein.}, } @article {pmid15256004, year = {2004}, author = {Cvrcková, F and Novotný, M and Pícková, D and Zárský, V}, title = {Formin homology 2 domains occur in multiple contexts in angiosperms.}, journal = {BMC genomics}, volume = {5}, number = {1}, pages = {44}, pmid = {15256004}, issn = {1471-2164}, mesh = {Actins/chemistry ; Amino Acid Sequence ; Arabidopsis/chemistry/genetics ; Conserved Sequence ; Cytoskeletal Proteins/*chemistry/genetics ; *Genes, Plant ; Magnoliopsida/*chemistry/genetics ; Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid ; }, abstract = {BACKGROUND: Involvement of conservative molecular modules and cellular mechanisms in the widely diversified processes of eukaryotic cell morphogenesis leads to the intriguing question: how do similar proteins contribute to dissimilar morphogenetic outputs. Formins (FH2 proteins) play a central part in the control of actin organization and dynamics, providing a good example of evolutionarily versatile use of a conserved protein domain in the context of a variety of lineage-specific structural and signalling interactions.

RESULTS: In order to identify possible plant-specific sequence features within the FH2 protein family, we performed a detailed analysis of angiosperm formin-related sequences available in public databases, with particular focus on the complete Arabidopsis genome and the nearly finished rice genome sequence. This has led to revision of the current annotation of half of the 22 Arabidopsis formin-related genes. Comparative analysis of the two plant genomes revealed a good conservation of the previously described two subfamilies of plant formins (Class I and Class II), as well as several subfamilies within them that appear to predate the separation of monocot and dicot plants. Moreover, a number of plant Class II formins share an additional conserved domain, related to the protein phosphatase/tensin/auxilin fold. However, considerable inter-species variability sets limits to generalization of any functional conclusions reached on a single species such as Arabidopsis.

CONCLUSIONS: The plant-specific domain context of the conserved FH2 domain, as well as plant-specific features of the domain itself, may reflect distinct functional requirements in plant cells. The variability of formin structures found in plants far exceeds that known from both fungi and metazoans, suggesting a possible contribution of FH2 proteins in the evolution of the plant type of multicellularity.}, } @article {pmid15254542, year = {2004}, author = {Aggarwal, BD and Calvi, BR}, title = {Chromatin regulates origin activity in Drosophila follicle cells.}, journal = {Nature}, volume = {430}, number = {6997}, pages = {372-376}, doi = {10.1038/nature02694}, pmid = {15254542}, issn = {1476-4687}, mesh = {Acetylation/drug effects ; Amanitins/pharmacology ; Animals ; Butyrates/pharmacology ; Chorion/cytology/drug effects/metabolism ; Chromatin/drug effects/genetics/*metabolism ; *DNA Replication/drug effects ; DNA-Binding Proteins/metabolism ; Drosophila Proteins ; Drosophila melanogaster/*cytology/*genetics ; Female ; Histone Deacetylase 1 ; Histone Deacetylase Inhibitors ; Histone Deacetylases/genetics/metabolism ; Histones/chemistry/metabolism ; Hot Temperature ; Hydroxamic Acids/pharmacology ; In Situ Hybridization, Fluorescence ; Mutation/genetics ; Nucleosomes/drug effects/genetics/metabolism ; Organ Specificity ; Origin Recognition Complex ; Ovarian Follicle/*cytology/drug effects/*metabolism ; Replication Origin/drug effects/*physiology ; Repressor Proteins ; Transcription Factors/genetics/metabolism ; }, abstract = {It is widely believed that DNA replication in multicellular animals (metazoa) begins at specific origins to which a pre-replicative complex (pre-RC) binds. Nevertheless, a consensus sequence for origins has yet to be identified in metazoa. Origin identity can change during development, suggesting that there are epigenetic influences. A notable example of developmental specificity occurs in Drosophila, where somatic follicle cells of the ovary transition from genomic replication to exclusive re-replication at origins that control amplification of the eggshell (chorion) protein genes. Here we show that chromatin acetylation is critical for this developmental transition in origin specificity. We find that histones at the active origins are hyperacetylated, coincident with binding of the origin recognition complex (ORC). Mutation of the histone deacetylase (HDAC) Rpd3 induced genome-wide hyperacetylation, genomic replication and a redistribution of the origin-binding protein ORC2 in amplification-stage cells, independent of effects on transcription. Tethering Rpd3 or Polycomb proteins to the origin decreased its activity, whereas tethering the Chameau acetyltransferase increased origin activity. These results suggest that nucleosome acetylation and other epigenetic changes are important modulators of origin activity in metazoa.}, } @article {pmid15247501, year = {2004}, author = {Doljanski, F}, title = {The sculpturing role of fibroblast-like cells in morphogenesis.}, journal = {Perspectives in biology and medicine}, volume = {47}, number = {3}, pages = {339-356}, doi = {10.1353/pbm.2004.0048}, pmid = {15247501}, issn = {0031-5982}, mesh = {Animals ; Cell Adhesion ; Cell Communication ; Cell Differentiation ; Epithelial Cells/physiology ; Extracellular Matrix/*physiology ; Fibroblasts/*physiology ; Morphogenesis/*physiology ; Organ Culture Techniques ; Pseudopodia/physiology ; Sea Urchins/embryology ; Signal Transduction ; }, abstract = {Cells of multicellular organisms are semi-fluid creatures. Even when they form specific cell-cell adhesions, they cannot create a defined shape or a tissue-specific architecture. Cartilaginous organs, such as ears and noses, exemplify the fact that form is imprinted in the extracellular matrix (ECM), which leads to the conclusion that cells must have the ability to shape the ECM in which they reside. This seems to be true for most tissues. The role of the ECM as an integrator of cells into functional assemblies with defined architecture is unique to multicellular organisms. The evolution of multicellularity became possible as a consequence of cells acquiring two new properties: first, cell surface macromolecular complexes that function in cell-cell binding; and, second, an ECM that integrates cells into three-dimensional structures. These two new properties allowed the evolution of the two basic types of cells-epithelial and mesenchymal. The appearance of the latter, a fibroblast-like cell with abundant filopodia, enabled the sculpturing of the ECM and the formation of complex tissue-specific architectures.}, } @article {pmid15246533, year = {2004}, author = {Bhatt, AM and Zhang, Q and Harris, SA and White-Cooper, H and Dickinson, H}, title = {Gene structure and molecular analysis of Arabidopsis thaliana ALWAYS EARLY homologs.}, journal = {Gene}, volume = {336}, number = {2}, pages = {219-229}, doi = {10.1016/j.gene.2004.03.033}, pmid = {15246533}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Arabidopsis/*genetics ; Arabidopsis Proteins/*genetics/metabolism ; Base Sequence ; Binding Sites/genetics ; Cell Nucleus/metabolism ; Cloning, Molecular ; DNA, Complementary/chemistry/genetics ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Microscopy, Confocal ; Molecular Sequence Data ; Phylogeny ; Promoter Regions, Genetic/genetics ; Recombinant Fusion Proteins/genetics/metabolism ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; TATA Box/genetics ; Tobacco/cytology ; }, abstract = {Drosophila always early (aly) is essential for spermatogenesis, and is related to the LIN-9 protein of Caenorhabditis elegans; lin-9 is a class B Synthetic Multivulva gene (synMuvB) required for gonadal sheath development. Aly/LIN-9 have two conserved regions, called domains 1 and 2, which have been identified in homologous proteins from several multicellular eukaryotes, including the model plant Arabidopsis thaliana. We cloned and sequenced cDNAs of three different A. thaliana ALWAYS EARLY homologs (AtALY1, AtALY2 and AtALY3), analysed the expression pattern of these three genes and show that AtALY1, like Aly, is nuclear localised. We also demonstrate that the plant homologs of aly/lin-9 contain an additional N-terminal myb domain not present in the animal Aly/LIN-9 proteins, and that part of the ALY/LIN-9 conserved domain 1 in the predicted plant proteins is related to the TUDOR domain.}, } @article {pmid15246321, year = {2004}, author = {Nguewa, PA and Fuertes, MA and Valladares, B and Alonso, C and Pérez, JM}, title = {Programmed cell death in trypanosomatids: a way to maximize their biological fitness?.}, journal = {Trends in parasitology}, volume = {20}, number = {8}, pages = {375-380}, doi = {10.1016/j.pt.2004.05.006}, pmid = {15246321}, issn = {1471-4922}, mesh = {Animals ; Apoptosis/*physiology ; Biological Evolution ; Humans ; Leishmania/*physiology ; Leishmaniasis/parasitology ; Selection, Genetic ; Trypanosoma/*physiology ; Trypanosomiasis/parasitology ; }, abstract = {Programmed cell death (PCD) is a biochemical process that plays an essential role in the development of multicellular organisms. However, accumulating evidence indicates that PCD is also present in single-celled eukaryotes. Thus, trypanosomatids might be endowed with a PCD mechanism that is derived from ancestral death machinery. PCD in trypanosomatids could be a process without a defined function, inherited through eukaryotic cell evolution, which might be triggered in response to diverse stimuli and stress conditions. However, recent observations suggest that PCD might be used by trypanosomatids to maximize their biological fitness. Therefore, PCD could represent a potential pharmacological target for protozoan control.}, } @article {pmid15241605, year = {2004}, author = {Korb, J and Heinze, J}, title = {Multilevel selection and social evolution of insect societies.}, journal = {Die Naturwissenschaften}, volume = {91}, number = {6}, pages = {291-304}, pmid = {15241605}, issn = {0028-1042}, mesh = {Animals ; *Biological Evolution ; Female ; Insecta/*classification/*genetics ; Male ; Reproduction ; *Selection, Genetic ; Sexual Behavior, Animal ; *Social Behavior ; }, abstract = {How sterile, altruistic worker castes have evolved in social insects and how they are maintained have long been central topics in evolutionary biology. With the advance of kin selection theory, insect societies, in particular those of haplodiploid bees, ants, and wasps, have become highly suitable model systems for investigating the details of social evolution and recently also how within-group conflicts are resolved. Because insect societies typically do not consist of clones, conflicts among nestmates arise, for example about the partitioning of reproduction and the allocation of resources towards male and female sexuals. Variation in relatedness among group members therefore appears to have a profound influence on the social structure of groups. However, insect societies appear to be remarkably robust against such variation: division of labor and task allocation are often organized in more or less the same way in societies with high as in those with very low nestmate relatedness. To explain the discrepancy between predictions from kin structure and empirical data, it was suggested that constraints-such as the lack of power or information-prevent individuals from pursuing their own selfish interests. Applying a multilevel selection approach shows that these constraints are in fact group-level adaptation preventing or resolving intracolonial conflict. The mechanisms of conflict resolution in insect societies are similar to those at other levels in the biological hierarchy (e.g., in the genome or multicellular organisms): alignment of interests, fair lottery, and social control. Insect societies can thus be regarded as a level of selection with novelties that provide benefits beyond the scope of a solitary life. Therefore, relatedness is less important for the maintenance of insect societies, although it played a fundamental role in their evolution.}, } @article {pmid15238157, year = {2004}, author = {Craxton, M}, title = {Synaptotagmin gene content of the sequenced genomes.}, journal = {BMC genomics}, volume = {5}, number = {1}, pages = {43}, pmid = {15238157}, issn = {1471-2164}, mesh = {Alternative Splicing ; Amino Acid Sequence ; Animals ; Anopheles/genetics ; Arabidopsis/genetics ; Caenorhabditis elegans/genetics ; Calcium-Binding Proteins/*genetics ; Ciona intestinalis/genetics ; Drosophila melanogaster/genetics ; Genes ; *Genome ; Humans ; Membrane Glycoproteins/*genetics ; Mice/genetics ; Molecular Sequence Data ; Multigene Family ; Nerve Tissue Proteins/*genetics ; Oryza/genetics ; Phylogeny ; Rats/genetics ; Rats, Sprague-Dawley/genetics ; Sequence Homology ; Synaptotagmins ; Takifugu/genetics ; Zebrafish/genetics ; }, abstract = {BACKGROUND: Synaptotagmins exist as a large gene family in mammals. There is much interest in the function of certain family members which act crucially in the regulated synaptic vesicle exocytosis required for efficient neurotransmission. Knowledge of the functions of other family members is relatively poor and the presence of Synaptotagmin genes in plants indicates a role for the family as a whole which is wider than neurotransmission. Identification of the Synaptotagmin genes within completely sequenced genomes can provide the entire Synaptotagmin gene complement of each sequenced organism. Defining the detailed structures of all the Synaptotagmin genes and their encoded products can provide a useful resource for functional studies and a deeper understanding of the evolution of the gene family. The current rapid increase in the number of sequenced genomes from different branches of the tree of life, together with the public deposition of evolutionarily diverse transcript sequences make such studies worthwhile.

RESULTS: I have compiled a detailed list of the Synaptotagmin genes of Caenorhabditis, Anopheles, Drosophila, Ciona, Danio, Fugu, Mus, Homo, Arabidopsis and Oryza by examining genomic and transcript sequences from public sequence databases together with some transcript sequences obtained by cDNA library screening and RT-PCR. I have compared all of the genes and investigated the relationship between plant Synaptotagmins and their non-Synaptotagmin counterparts.

CONCLUSIONS: I have identified and compared 98 Synaptotagmin genes from 10 sequenced genomes. Detailed comparison of transcript sequences reveals abundant and complex variation in Synaptotagmin gene expression and indicates the presence of Synaptotagmin genes in all animals and land plants. Amino acid sequence comparisons indicate patterns of conservation and diversity in function. Phylogenetic analysis shows the origin of Synaptotagmins in multicellular eukaryotes and their great diversification in animals. Synaptotagmins occur in land plants and animals in combinations of 4-16 in different species. The detailed delineation of the Synaptotagmin genes presented here, will allow easier identification of Synaptotagmins in future. Since the functional roles of many of these genes are unknown, this gene collection provides a useful resource for future studies.}, } @article {pmid15226389, year = {2004}, author = {Kessels, MM and Qualmann, B}, title = {The syndapin protein family: linking membrane trafficking with the cytoskeleton.}, journal = {Journal of cell science}, volume = {117}, number = {Pt 15}, pages = {3077-3086}, doi = {10.1242/jcs.01290}, pmid = {15226389}, issn = {0021-9533}, mesh = {Actin-Related Protein 2 ; Actin-Related Protein 3 ; Actins/metabolism ; Adaptor Proteins, Signal Transducing ; Animals ; Carrier Proteins/metabolism/*physiology ; Cell Membrane/*metabolism ; Chickens ; Cytoskeletal Proteins/metabolism ; Cytoskeleton/*metabolism ; Endocytosis ; Golgi Apparatus/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; Mice ; Models, Biological ; Nerve Tissue Proteins/chemistry ; Neuropeptides/metabolism/*physiology ; Phosphoproteins/physiology ; Phylogeny ; Protein Binding ; Protein Transport ; Proteins/physiology ; Rats ; Signal Transduction ; Wiskott-Aldrich Syndrome Protein, Neuronal ; }, abstract = {Syndapins--also called PACSINs--are highly conserved Src-homology 3 (SH3)-domain-containing proteins that seem to exist in all multicellular eukaryotes. They interact with the large GTPase dynamin and several other proteins implicated in vesicle trafficking. Syndapin-dynamin complexes appear to play an important role in vesicle fission at different donor membranes, including the plasma membrane (endocytosis) and Golgi membranes. In addition, syndapins are implicated in later steps of vesicle cycling in neuronal and non-neuronal cells. Syndapins also interact with N-WASP, a potent activator of the Arp2/3 complex that forms a critical part of the actin polymerization machinery. Syndapin oligomers can thereby couple bursts of actin polymerization with the vesicle fission step involving dynamins. This allows newly formed vesicles to move away from the donor membrane driven by actin polymerization. Syndapins also engage in additional interactions with molecules involved in several signal transduction pathways, producing crosstalk at the interface between membrane trafficking and the cytoskeleton. Given the distinct expression patterns of the different syndapins and their splice forms, these proteins could have isoform-specific functions.}, } @article {pmid15221385, year = {2004}, author = {Geldner, N}, title = {The plant endosomal system--its structure and role in signal transduction and plant development.}, journal = {Planta}, volume = {219}, number = {4}, pages = {547-560}, pmid = {15221385}, issn = {0032-0935}, mesh = {Animals ; Arabidopsis/growth & development/metabolism ; Drosophila/growth & development/metabolism ; Endosomes/*metabolism/physiology ; Models, Molecular ; Phylogeny ; Plant Development ; Plants/*metabolism ; *Signal Transduction ; }, abstract = {Endosomes are highly dynamic membrane systems that receive endocytosed plasma membrane proteins and sort them for either degradation or recycling back to the cell surface. In addition, they receive newly synthesised proteins destined for vacuolar/lysosomal compartments. Sorting in the endosomes is necessary for the establishment and maintenance of cell polarity and it is needed to control levels and function of receptors and transporters at the cellular surface. Both processes are crucial for correct cell behaviour during tissue and organ development and for intercellular communication in general. It has therefore become an imperative to investigate structure and function of the endosomal system if we want to obtain a deeper mechanistic understanding of signal transduction and development. This review will compare our current understanding of endosomal trafficking in animals and yeast with what is known in plants, and will highlight some important breakthroughs in our understanding of the role of endosomes in signal transduction and multicellular development in Drosophila, as well as in Arabidopsis.}, } @article {pmid15219781, year = {2004}, author = {Müller, WE and Wiens, M and Adell, T and Gamulin, V and Schröder, HC and Müller, IM}, title = {Bauplan of urmetazoa: basis for genetic complexity of metazoa.}, journal = {International review of cytology}, volume = {235}, number = {}, pages = {53-92}, doi = {10.1016/S0074-7696(04)35002-3}, pmid = {15219781}, issn = {0074-7696}, mesh = {Animals ; Body Patterning/*genetics ; Cell Adhesion Molecules/genetics ; Cell Differentiation/*genetics ; Evolution, Molecular ; Gene Expression Regulation, Developmental/*genetics ; Phylogeny ; Porifera/cytology/*genetics/*growth & development ; }, abstract = {Sponges were first grouped to the animal-plants or plant-animals then to the Zoophyta or Mesozoa and finally to the Parazoa. Only after the application of molecular biological techniques was it possible to place the Porifera monophyletically with the other metazoan phyla, justifying a unification of all multicellular animals to only one kingdom, the Metazoa. The first strong support came from the discovery that cell-cell and cell-matrix adhesion molecules that were cloned from sponges and were subsequently expressed share a high DNA sequence and protein function similarity with the corresponding molecules of other metazoans. Besides these evolutionary novelties for Metazoa, sponges also have morphogens and transcription factors in common with other metazoan phyla. Surprisingly, even those elements exist in Porifera, which are characteristic for pattern and axis formation. Recent studies showed that epithelial layers of sponges are sealed against the extracellular milieu through tight-junction proteins. The cell culture system from sponges, the primmorphs, was suitable for understanding morphogenetic events. Finally, stem cell marker genes were isolated, which underscored that sponge cells have the capacity to differentiate. In the relatively short period of time, approximately 200 million years, the basic pathways had to be established that allowed the transition for multicellular organisms to a colonial system through the formation of adhesion molecules; based on the development of a complex immune system and the apoptotic machinery of an integrated system, the Urmetazoa, which evolved approximately 800 million years ago, could be reached. Hence, the Bauplan of the hypothetical Urmetazoa can now be constructed according to genomic regulatory systems similar to those found in higher Metazoa. These data caused a paradigmatic change; the Porifera are complex and simple but by far not primitive.}, } @article {pmid15199962, year = {2004}, author = {Bulet, P and Stöcklin, R and Menin, L}, title = {Anti-microbial peptides: from invertebrates to vertebrates.}, journal = {Immunological reviews}, volume = {198}, number = {}, pages = {169-184}, doi = {10.1111/j.0105-2896.2004.0124.x}, pmid = {15199962}, issn = {0105-2896}, mesh = {Amino Acid Sequence ; Animals ; Anti-Bacterial Agents/chemistry ; Antimicrobial Cationic Peptides/*chemistry ; Invertebrates/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Peptides, Cyclic/chemistry ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Vertebrates/*metabolism ; }, abstract = {Gene-encoded anti-microbial peptides (AMPs) are widespread in nature, as they are synthesized by microorganisms as well as by multicellular organisms from both the vegetal and the animal kingdoms. These naturally occurring AMPs form a first line of host defense against pathogens and are involved in innate immunity. Depending on their tissue distribution, AMPs ensure either a systemic or a local protection of the organism against environmental pathogens. They are classified into three major groups: (i) peptides with an alpha-helical conformation (insect cecropins, magainins, etc.), (ii) cyclic and open-ended cyclic peptides with pairs of cysteine residues (defensins, protegrin, etc.), and (iii) peptides with an over-representation of some amino acids (proline rich, histidine rich, etc.). Most AMPs display hydrophobic and cationic properties, have a molecular mass below 25-30 kDa, and adopt an amphipathic structure (alpha-helix, beta-hairpin-like beta-sheet, beta-sheet, or alpha-helix/beta-sheet mixed structures) that is believed to be essential to their anti-microbial action. Interestingly, in recent years, a series of novel AMPs have been discovered as processed forms of large proteins. Despite the extreme diversity in their primary and secondary structures, all natural AMPs have the in vitro particularity to affect a large number of microorganisms (bacteria, fungi, yeast, virus, etc.) with identical or complementary activity spectra. This review focuses on AMPs forming alpha-helices, beta-hairpin-like beta-sheets, beta-sheets, or alpha-helix/beta-sheet mixed structures from invertebrate and vertebrate origins. These molecules show some promise for therapeutic use.}, } @article {pmid15189994, year = {2004}, author = {Stiller, JW and Cook, MS}, title = {Functional unit of the RNA polymerase II C-terminal domain lies within heptapeptide pairs.}, journal = {Eukaryotic cell}, volume = {3}, number = {3}, pages = {735-740}, pmid = {15189994}, issn = {1535-9778}, mesh = {Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Cloning, Molecular ; Consensus Sequence/genetics ; Eukaryota/*genetics ; *Evolution, Molecular ; Fungi/*genetics ; Molecular Sequence Data ; Phylogeny ; RNA Polymerase II/*genetics ; Saccharomyces cerevisiae/*genetics ; }, abstract = {Unlike all other RNA polymerases, the largest subunit (RPB1) of eukaryotic DNA-dependent RNA polymerase II (RNAP II) has a C-terminal domain (CTD) comprising tandemly repeated heptapeptides with the consensus sequence Y-S-P-T-S-P-S. The tandem structure, heptad consensus, and most key functions of the CTD are conserved between yeast and mammals. In fact, all metazoans, fungi, and green plants examined to date, as well as the nearest protistan relatives of these multicellular groups, contain a tandemly repeated CTD. In contrast, the RNAP II largest subunits from many other eukaryotic organisms have a highly degenerate C terminus or show no semblance of the CTD whatsoever. The reasons for intense stabilizing selection on CTD structure in certain eukaryotes, and its apparent absence in others, are unknown. Here we demonstrate, through in vivo genetic complementation, that the essential functional unit of the yeast CTD is contained within pairs of heptapeptides. Insertion of a single alanine residue between diheptads has little phenotypic effect, while increasing the distance between diheptads produces a mostly quantitative effect on yeast cell growth. We further explore structural constraints on the CTD within an evolutionary context and propose selective mechanisms that could maintain a global tandem structure across hundreds of millions of years of eukaryotic evolution.}, } @article {pmid15186489, year = {2004}, author = {Budd, A and Blandin, S and Levashina, EA and Gibson, TJ}, title = {Bacterial alpha2-macroglobulins: colonization factors acquired by horizontal gene transfer from the metazoan genome?.}, journal = {Genome biology}, volume = {5}, number = {6}, pages = {R38}, pmid = {15186489}, issn = {1474-760X}, mesh = {Alphaproteobacteria/genetics ; Amino Acid Sequence/genetics ; Bacterial Proteins/genetics ; Bacteroidetes/genetics ; Betaproteobacteria/genetics ; Computational Biology/methods ; Cyanobacteria/genetics ; Databases, Protein ; Fusobacteria/genetics ; Gene Expression Profiling/methods ; Gene Transfer, Horizontal/*genetics ; Genes, Bacterial/genetics ; *Genome, Bacterial ; Humans ; Magnetospirillum/genetics ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis/methods ; Phylogeny ; Spirochaetales/genetics ; alpha-Macroglobulins/*genetics ; }, abstract = {BACKGROUND: Invasive bacteria are known to have captured and adapted eukaryotic host genes. They also readily acquire colonizing genes from other bacteria by horizontal gene transfer. Closely related species such as Helicobacter pylori and Helicobacter hepaticus, which exploit different host tissues, share almost none of their colonization genes. The protease inhibitor alpha2-macroglobulin provides a major metazoan defense against invasive bacteria, trapping attacking proteases required by parasites for successful invasion.

RESULTS: Database searches with metazoan alpha2-macroglobulin sequences revealed homologous sequences in bacterial proteomes. The bacterial alpha2-macroglobulin phylogenetic distribution is patchy and violates the vertical descent model. Bacterial alpha2-macroglobulin genes are found in diverse clades, including purple bacteria (proteobacteria), fusobacteria, spirochetes, bacteroidetes, deinococcids, cyanobacteria, planctomycetes and thermotogae. Most bacterial species with bacterial alpha2-macroglobulin genes exploit higher eukaryotes (multicellular plants and animals) as hosts. Both pathogenically invasive and saprophytically colonizing species possess bacterial alpha2-macroglobulins, indicating that bacterial alpha2-macroglobulin is a colonization rather than a virulence factor.

CONCLUSIONS: Metazoan alpha2-macroglobulins inhibit proteases of pathogens. The bacterial homologs may function in reverse to block host antimicrobial defenses. Alpha2-macroglobulin was probably acquired one or more times from metazoan hosts and has then spread widely through other colonizing bacterial species by more than 10 independent horizontal gene transfers. yfhM-like bacterial alpha2-macroglobulin genes are often found tightly linked with pbpC, encoding an atypical peptidoglycan transglycosylase, PBP1C, that does not function in vegetative peptidoglycan synthesis. We suggest that YfhM and PBP1C are coupled together as a periplasmic defense and repair system. Bacterial alpha2-macroglobulins might provide useful targets for enhancing vaccine efficacy in combating infections.}, } @article {pmid15177691, year = {2004}, author = {Haag, KL and Alves-Junior, L and Zaha, A and Ayala, FJ}, title = {Contingent, non-neutral evolution in a multicellular parasite: natural selection and gene conversion in the Echinococcus granulosus antigen B gene family.}, journal = {Gene}, volume = {333}, number = {}, pages = {157-167}, doi = {10.1016/j.gene.2004.02.027}, pmid = {15177691}, issn = {0378-1119}, support = {GM42397/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Antigens, Helminth/genetics ; Base Sequence ; Cloning, Molecular ; DNA, Helminth/chemistry/genetics ; Echinococcus/*genetics/immunology ; *Evolution, Molecular ; *Gene Conversion ; Helminth Proteins/*genetics ; Lipoproteins/*genetics ; Molecular Sequence Data ; Phylogeny ; Polymorphism, Genetic ; *Selection, Genetic ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; }, abstract = {Recent studies have demonstrated that the Echinococcus granulosus antigen B (AgB) interferes with the intermediate hosts' immune response and is encoded by a multigene family. The number of members within the family is still uncertain, but there are several evidences of a large genetic variability. The E. granulosus AgB genomic sequences available in nucleotide databases can be grouped into four clades, corresponding to genes EgAgB1, EgAgB2, EgAgB3 and EgAgB4. In the present study, we use PCR amplifications followed by cloning and sequencing to evaluate the genetic variability for AgB isoforms. Two pairs of primers were independently used for PCR amplification. Both PCR reactions from each of three isolated protoscolex (larvae) were cloned in a plasmid vector and the plasmid inserts of 30 colonies from each cloning experiment were sequenced. Using phylogenetic tools, the 113 EgAgB clones are classified as follows: 25 are related to EgAgB1, 24 to EgAgB2, 9 to EgAgB3 and 39 to EgAgB4. The remaining 16 clones form a separate cluster, which we name EgAgB5, more closely related to EgAgB3 than to any of the other genes. Within each gene group, a number of variant sequences occur, which differ from one another by one or few nucleotides. One EgAgB3 clone has a premature stop codon (pseudogene) and an EgAgB2 clone lacks the region corresponding to the intron. The overall variation cannot be explained by differences among the asexual protoscoleces, or by experimental artifacts. Using Echinococcuss AgB genes from other species/strains as outgroups, neutrality is rejected for EgAgB2, and balancing selection is detected for EgAgB5, which also seems to be involved in gene conversion. We suggest that EgAgB1-EgAgB5 represent a family of contingency genes, that is, genes that are variably expressed, so that some but not others are expressed in each individual parasite. Contingency genes are common in parasitic protozoa and other microparasites, but the EgAgB family is the first set identified in a multicellular parasite.}, } @article {pmid15170403, year = {2004}, author = {Nudleman, E and Kaiser, D}, title = {Pulling together with type IV pili.}, journal = {Journal of molecular microbiology and biotechnology}, volume = {7}, number = {1-2}, pages = {52-62}, doi = {10.1159/000077869}, pmid = {15170403}, issn = {1464-1801}, mesh = {Bacteria/classification ; *Bacterial Physiological Phenomena ; Bacterial Proteins/chemistry/*physiology ; Fimbriae, Bacterial/*physiology/*ultrastructure ; Models, Molecular ; Movement ; Phylogeny ; Protein Conformation ; Protein Structure, Secondary ; }, abstract = {Type IV pili are an efficient and versatile device for bacterial surface motility. They are widespread among the beta-, gamma-, and delta-proteobacteria and the cyanobacteria. Within that diversity, there is a core of conserved proteins that includes the pilin (PilA), the motors PilB and PilT, and various components of pilus biogenesis and assembly, PilC, PilD, PilM, PilN, PilO, PilP, and PilQ. Progress has been made in understanding the motor and the secretory functions. PilT is a motor protein that catalyzes pilus retraction; PilB may play a similar role in pilus extension. Type IV pili are multifunctional complexes that can act as bacterial virulence factors because pilus-based motility is used to spread pathogens over the surface of a tissue, or to build multicellular structures such as biofilms and fruiting bodies.}, } @article {pmid15165228, year = {2004}, author = {Baker, DA and Kelly, JM}, title = {Structure, function and evolution of microbial adenylyl and guanylyl cyclases.}, journal = {Molecular microbiology}, volume = {52}, number = {5}, pages = {1229-1242}, doi = {10.1111/j.1365-2958.2004.04067.x}, pmid = {15165228}, issn = {0950-382X}, mesh = {*Adenylyl Cyclases/chemistry/classification/genetics/metabolism ; Amino Acid Sequence ; Animals ; Bacteria/*enzymology ; Cyclic AMP/metabolism ; Eukaryota/*enzymology ; Evolution, Molecular ; Fungi/*enzymology ; *Guanylate Cyclase/chemistry/classification/genetics/metabolism ; Humans ; Molecular Sequence Data ; Phylogeny ; Second Messenger Systems/physiology ; Sequence Alignment ; }, abstract = {Cells respond to signals of both environmental and biological origin. Responses are often receptor mediated and result in the synthesis of so-called second messengers that then provide a link between extracellular signals and downstream events, including changes in gene expression. Cyclic nucleotides (cAMP and cGMP) are among the most widely studied of this class of molecule. Research on their function and mode of action has been a paradigm for signal transduction systems and has shaped our understanding of this important area of biology. Cyclic nucleotides have diverse regulatory roles in both unicellular and multicellular organisms, highlighting the utility and success of this system of molecular communication. This review will examine the structural diversity of microbial adenylyl and guanylyl cyclases, the enzymes that synthesize cAMP and cGMP respectively. We will address the relationship of structure to biological function and speculate on the complex origin of these crucial regulatory molecules. A review is timely because the explosion of data from the various genome projects is providing new and exciting insights into protein function and evolution.}, } @article {pmid15163364, year = {2004}, author = {Huang, S}, title = {Back to the biology in systems biology: what can we learn from biomolecular networks?.}, journal = {Briefings in functional genomics & proteomics}, volume = {2}, number = {4}, pages = {279-297}, doi = {10.1093/bfgp/2.4.279}, pmid = {15163364}, issn = {1473-9550}, mesh = {Animals ; Biological Evolution ; Biology/*methods ; Cell Lineage ; Computers ; Genome ; Humans ; Learning ; Models, Genetic ; Phenotype ; Software ; *Systems Analysis ; Systems Theory ; }, abstract = {Genome-scale molecular networks, including protein interaction and gene regulatory networks, have taken centre stage in the investigation of the burgeoning disciplines of systems biology and biocomplexity. What do networks tell us? Some see in networks simply the comprehensive, detailed description of all cellular pathways, others seek in networks simple, higher-order qualities that emerge from the collective action of the individual pathways. This paper discusses networks from an encompassing category of thinking that will hopefully help readers to bridge the gap between these polarised viewpoints. Systems biology so far has emphasised the characterisation of large pathway maps. Now one has to ask: where is the actual biology in 'systems biology'? As structures midway between genome and phenome, and by serving as an 'extended genotype' or an 'elementary phenotype', molecular networks open a new window to the study of evolution and gene function in complex living systems. For the study of evolution, features in network topology offer a novel starting point for addressing the old debate on the relative contributions of natural selection versus intrinsic constraints to a particular trait. To study the function of genes, it is necessary not only to see them in the context of gene networks, but also to reach beyond describing network topology and to embrace the global dynamics of networks that will reveal higher-order, collective behaviour of the interacting genes. This will pave the way to understanding how the complexity of genome-wide molecular networks collapses to produce a robust whole-cell behaviour that manifests as tightly-regulated switching between distinct cell fates - the basis for multicellular life.}, } @article {pmid15159449, year = {2004}, author = {Turksen, K and Troy, TC}, title = {Barriers built on claudins.}, journal = {Journal of cell science}, volume = {117}, number = {Pt 12}, pages = {2435-2447}, doi = {10.1242/jcs.01235}, pmid = {15159449}, issn = {0021-9533}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Biological Transport ; Cell Membrane/*chemistry ; Cell Membrane Permeability ; Cell Polarity ; Conserved Sequence ; Evolution, Molecular ; Gene Expression ; Humans ; Membrane Proteins/*chemistry/genetics/*metabolism ; Models, Biological ; Molecular Sequence Data ; Molecular Weight ; Protein Structure, Tertiary ; Sequence Analysis, Protein ; Sequence Homology, Amino Acid ; *Tight Junctions ; Tissue Distribution ; }, abstract = {The fundamental functions of epithelia and endothelia in multicellular organisms are to separate compositionally distinct compartments and regulate the exchange of small solutes and other substances between them. Tight junctions (TJs) between adjacent cells constitute the barrier to the passage of ions and molecules through the paracellular pathway and function as a 'fence' within the plasma membrane to create and maintain apical and basolateral membrane domains. How TJs achieve this is only beginning to be understood. Recently identified components of TJs include the claudins, a family of four-transmembrane-span proteins that are prime candidates for molecules that function in TJ permeability. Their identification and characterization have provided new insight into the diversity of different TJs and heterogeneity of barrier functions in different epithelia and endothelia.}, } @article {pmid15145062, year = {2004}, author = {Girard-Reydet, C and Grégoire, D and Vassetzky, Y and Méchali, M}, title = {DNA replication initiates at domains overlapping with nuclear matrix attachment regions in the xenopus and mouse c-myc promoter.}, journal = {Gene}, volume = {332}, number = {}, pages = {129-138}, doi = {10.1016/j.gene.2004.02.031}, pmid = {15145062}, issn = {0378-1119}, mesh = {Animals ; Binding Sites/genetics ; Cell Line, Tumor ; DNA/biosynthesis/genetics ; DNA Replication/*genetics ; Embryo, Nonmammalian/metabolism ; Embryonic Development ; Mice ; Nuclear Matrix/*genetics ; Promoter Regions, Genetic/*genetics ; Proto-Oncogene Proteins c-myc/*genetics ; Xenopus ; }, abstract = {Only a very few origins have been mapped in different multicellular organisms, and they do not share detectable consensus sequence elements. Moreover, it is not clear if origins are localized at similar positions in the corresponding locus in genomes of different organisms. Here, we have mapped DNA replication origins in the c-myc locus both in Xenopus and mouse, allowing a comparison of the corresponding sites in three different animal species (Xenopus, mouse, human). An origin of DNA replication is present in the three homologous c-myc loci. In Xenopus, a main DNA replication origin was located 3 kilobases (kb) upstream of the active c-myc promoter, whereas, in mouse, we detected an origin 1 kb upstream of the promoter, as previously mapped in human c-myc. We also identified a nuclear matrix attachment region in both Xenopus and mouse, which is localized to two different regions of the c-myc promoter region. However, in both cases, the nuclear matrix attachment sites are close to the DNA replication origin mapped in the locus. These data suggest that global features of chromatin organization in different organisms may contribute to DNA replication origin localization.}, } @article {pmid15129284, year = {2004}, author = {Kers, JA and Wach, MJ and Krasnoff, SB and Widom, J and Cameron, KD and Bukhalid, RA and Gibson, DM and Crane, BR and Loria, R}, title = {Nitration of a peptide phytotoxin by bacterial nitric oxide synthase.}, journal = {Nature}, volume = {429}, number = {6987}, pages = {79-82}, doi = {10.1038/nature02504}, pmid = {15129284}, issn = {1476-4687}, mesh = {Arginine/*analogs & derivatives/metabolism ; Gene Deletion ; Genes, Bacterial/genetics ; Indoles/chemistry/*metabolism ; Molecular Sequence Data ; Nitrates/*metabolism ; Nitric Oxide Synthase/genetics/*metabolism ; Nitrites/metabolism ; Nitrogen/metabolism ; Piperazines/chemistry/*metabolism ; Plants/drug effects ; Streptomyces/*enzymology/genetics ; Toxins, Biological/chemistry/metabolism ; }, abstract = {Nitric oxide (NO) is a potent intercellular signal in mammals that mediates key aspects of blood pressure, hormone release, nerve transmission and the immune response of higher organisms. Proteins homologous to full-length mammalian nitric oxide synthases (NOSs) are found in lower multicellular organisms. Recently, genome sequencing has shown that some bacteria contain genes coding for truncated NOS proteins; this is consistent with reports of NOS-like activities in bacterial extracts. Biological functions for bacterial NOSs are unknown, but have been presumed to be analogous to their role in mammals. Here we describe a gene in the plant pathogen Streptomyces turgidiscabies that encodes a NOS homologue, and we reveal its role in nitrating a dipeptide phytotoxin required for plant pathogenicity. High similarity between bacterial NOSs indicates a general function in biosynthetic nitration; thus, bacterial NOSs constitute a new class of enzymes. Here we show that the primary function of Streptomyces NOS is radically different from that of mammalian NOS. Surprisingly, mammalian NO signalling and bacterial biosynthetic nitration share an evolutionary origin.}, } @article {pmid15107848, year = {2004}, author = {Zhang, H and Smolen, GA and Palmer, R and Christoforou, A and van den Heuvel, S and Haber, DA}, title = {SUMO modification is required for in vivo Hox gene regulation by the Caenorhabditis elegans Polycomb group protein SOP-2.}, journal = {Nature genetics}, volume = {36}, number = {5}, pages = {507-511}, doi = {10.1038/ng1336}, pmid = {15107848}, issn = {1061-4036}, mesh = {Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/genetics/metabolism ; *Caenorhabditis elegans Proteins ; Cell Nucleus/*physiology ; Conserved Sequence ; Evolution, Molecular ; *Gene Expression Regulation ; Genes, Homeobox/*physiology ; Green Fluorescent Proteins ; Luminescent Proteins/metabolism ; Neurons/metabolism ; *Protein Processing, Post-Translational ; Protein Structure, Tertiary ; Protein Transport ; RNA Interference ; Recombinant Fusion Proteins ; Repressor Proteins/genetics/*metabolism ; SUMO-1 Protein/genetics/*metabolism ; Saccharomyces cerevisiae ; Two-Hybrid System Techniques ; Ubiquitin-Conjugating Enzymes/*metabolism ; }, abstract = {Post-translational modification of proteins by the ubiquitin-like molecule SUMO (sumoylation) regulates their subcellular localization and affects their functional properties in vitro, but the physiological function of sumoylation in multicellular organisms is largely unknown. Here, we show that the C. elegans Polycomb group (PcG) protein SOP-2 interacts with the SUMO-conjugating enzyme UBC-9 through its evolutionarily conserved SAM domain. Sumoylation of SOP-2 is required for its localization to nuclear bodies in vivo and for its physiological repression of Hox genes. Global disruption of sumoylation phenocopies a sop-2 mutation by causing ectopic Hox gene expression and homeotic transformations. Chimeric constructs in which the SOP-2 SAM domain is replaced with that derived from fruit fly or mammalian PcG proteins, but not those in which the SOP-2 SAM domain is replaced with the SAM domains of non-PcG proteins, confer appropriate in vivo nuclear localization and Hox gene repression. These observations indicate that sumoylation of PcG proteins, modulated by their evolutionarily conserved SAM domain, is essential to their physiological repression of Hox genes.}, } @article {pmid15102375, year = {2004}, author = {Wang, ZY and He, JX}, title = {Brassinosteroid signal transduction--choices of signals and receptors.}, journal = {Trends in plant science}, volume = {9}, number = {2}, pages = {91-96}, doi = {10.1016/j.tplants.2003.12.009}, pmid = {15102375}, issn = {1360-1385}, support = {R01 GM066258/GM/NIGMS NIH HHS/United States ; }, mesh = {Brassinosteroids ; Cholestanols/*metabolism ; Ligands ; Solanum lycopersicum/*metabolism ; Peptides/metabolism ; Plant Growth Regulators/metabolism ; Protein Kinases/metabolism ; Receptors, Cell Surface/genetics/metabolism ; Receptors, Steroid ; *Signal Transduction ; Steroids, Heterocyclic/*metabolism ; }, abstract = {Small signaling molecules that mediate cell-cell communication are essential for developmental regulation in multicellular organisms. Among them are the steroids and peptide hormones that regulate growth in both plants and animals. In plants, brassinosteroids (BRs) are perceived by the cell surface receptor kinase BRI1, which is distinct from the animal steroid receptors. Identification of components of the BR signaling pathway has revealed similarities to other animal and plant signal transduction pathways. Recent studies demonstrated that tomato BRI1 (tBRI1) perceives both BR and the peptide hormone systemin, raising new questions about the molecular mechanism and evolution of receptor-ligand specificity.}, } @article {pmid15094398, year = {2004}, author = {Sona, S and Suzuki, T and Ellington, WR}, title = {Cloning and expression of mitochondrial and protoflagellar creatine kinases from a marine sponge: implications for the origin of intracellular energy transport systems.}, journal = {Biochemical and biophysical research communications}, volume = {317}, number = {4}, pages = {1207-1214}, doi = {10.1016/j.bbrc.2004.03.176}, pmid = {15094398}, issn = {0006-291X}, mesh = {Amino Acid Sequence ; Animals ; Biological Transport ; Ciona intestinalis/enzymology ; Cloning, Molecular ; Creatine Kinase/*biosynthesis/chemistry/*genetics ; Cytoplasm/*enzymology ; Dimerization ; Energy Metabolism ; Escherichia coli/metabolism ; Isoenzymes ; Mice ; Mitochondria/*enzymology ; Molecular Sequence Data ; Phylogeny ; Polychaeta/enzymology ; Porifera/*enzymology ; Recombinant Proteins/biosynthesis/chemistry/genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {Creatine kinase (CK) plays a central role in energy transactions in cells displaying high and variable rates of ATP turnover. Cytoplasmic and mitochondrial CK genes code for isoforms which are targeted to distinct intracellular compartments often in close physical proximity to sites of ATP hydrolysis or synthesis. In certain lower groups a third CK gene is present which codes for a flagellar CK isoform consisting of three complete, fused CK domains. Recent work has shown that cytoplasmic, mitochondrial, and flagellar CKs are present in protochordates and in deuterostome and protostome invertebrates. We report here that the marine sponge Tethya aurantia, a representative of the oldest of all multi-cellular animal groups, expresses three unique CK transcripts. One of these CK transcripts codes for protein that has a mitochondrial targeting sequence and in a phylogenetic analysis is positioned at the base of the cluster containing mitochondrial CK sequences from invertebrates, protochordates, and vertebrates; it is clearly a mitochondrial CK. When expressed in Escherichia coli the mitochondrial form from T. aurantia was found to be dimeric unlike all other mitochondrial CKs which are typically octameric. The other two T. aurantia transcripts code for proteins that appear to be more closely related to flagellar CKs. These protoflagellar CKs were found to be dimers when expressed in Escherichia coli. Sponges last shared a common ancestor with higher animals as long as one billion years ago. The antiquity of intracellular localization, as evidenced by the presence of a true mitochondrial CK and protoflagellar CKs in the sponge T. aurantia, indicates that physical constraints on cellular energy transport were key, early driving forces in the evolution of this key enzyme system.}, } @article {pmid15087315, year = {2004}, author = {Fofanov, Y and Luo, Y and Katili, C and Wang, J and Belosludtsev, Y and Powdrill, T and Belapurkar, C and Fofanov, V and Li, TB and Chumakov, S and Pettitt, BM}, title = {How independent are the appearances of n-mers in different genomes?.}, journal = {Bioinformatics (Oxford, England)}, volume = {20}, number = {15}, pages = {2421-2428}, doi = {10.1093/bioinformatics/bth266}, pmid = {15087315}, issn = {1367-4803}, mesh = {Algorithms ; Base Sequence ; Chromosome Mapping/*methods ; Conserved Sequence/*genetics ; DNA Fingerprinting/*methods ; Evolution, Molecular ; *Models, Genetic ; *Models, Statistical ; Molecular Sequence Data ; Oligonucleotides/genetics ; Sequence Alignment/*methods ; Sequence Analysis, DNA/*methods ; Statistics as Topic ; }, abstract = {MOTIVATION: Analysis of statistical properties of DNA sequences is important for evolutional biology as well as for DNA probe and PCR technologies. These technologies, in turn, can be used for organism identification, which implies applications in the diagnosis of infectious diseases, environmental studies, etc.

RESULTS: We present results of the correlation analysis of distributions of the presence/absence of short nucleotide subsequences of different length ('n-mers', n = 5-20) in more than 1500 microbial and virus genomes, together with five genomes of multicellular organisms (including human). We calculate whether a given n-mer is present or absent (frequency of presence) in a given genome, which is not the usually calculated number of appearances of n-mers in one or more genomes (frequency of appearance). For organisms that are not close relatives of each other, the presence/absence of different 7-20mers in their genomes are not correlated. For close biological relatives, some correlation of the presence of n-mers in this range appears, but is not as strong as expected. Suppressed correlations among the n-mers present in different genomes leads to the possibility of using random sets of n-mers (with appropriately chosen n) to discriminate genomes of different organisms and possibly individual genomes of the same species including human with a low probability of error.}, } @article {pmid15085933, year = {2004}, author = {Krol, J and Krzyzosiak, WJ}, title = {Structural aspects of microRNA biogenesis.}, journal = {IUBMB life}, volume = {56}, number = {2}, pages = {95-100}, doi = {10.1080/15216540410001670142}, pmid = {15085933}, issn = {1521-6543}, mesh = {Animals ; Humans ; MicroRNAs/*biosynthesis/chemistry/metabolism ; Protein Structure, Quaternary ; RNA Precursors/metabolism ; Ribonuclease III/chemistry/*metabolism ; Substrate Specificity/physiology ; }, abstract = {One of the biggest surprises at the beginning of the 'post-genome era' was the discovery of numerous genes encoding microRNAs. They were found in genomes of such diverse organisms as Caenorhabditis elegans, Drosophila melanogaster, Arabidopsis thaliana, and Homo sapiens which implies their important role in multicellular life evolution. The number of microRNA genes is estimated to be nearly 1% of that of protein-coding genes. Their products, tiny RNAs, are thought to regulate gene expression during development, organogenesis, and very likely during many other processes, by hybridizing to their target mRNAs. The cellular functions of mRNAs that are regulated by microRNAs are only beginning to be revealed, and details of this regulation mechanism are still poorly understood. In this article we discuss the possible mechanisms of microRNA biogenesis with special emphasis on their structural aspects. We have focused on the factors and effects that may be responsible for the existing length differences between different microRNAs, and for the observed length heterogeneity within some individual microRNA species.}, } @article {pmid15031265, year = {2004}, author = {Mouchel, CF and Briggs, GC and Hardtke, CS}, title = {Natural genetic variation in Arabidopsis identifies BREVIS RADIX, a novel regulator of cell proliferation and elongation in the root.}, journal = {Genes & development}, volume = {18}, number = {6}, pages = {700-714}, pmid = {15031265}, issn = {0890-9369}, mesh = {Amino Acid Sequence ; Arabidopsis/genetics/*growth & development ; Arabidopsis Proteins/*genetics/metabolism ; Cell Division/*physiology ; *Gene Expression Regulation, Plant ; Molecular Sequence Data ; Phylogeny ; Plant Roots/*growth & development ; Sequence Alignment ; Sequence Analysis, DNA ; Transcription Factors/*genetics/metabolism ; Yeasts/genetics/physiology ; }, abstract = {Mutant analysis has been tremendously successful in deciphering the genetics of plant development. However, less is known about the molecular basis of morphological variation within species, which is caused by naturally occurring alleles. In this study, we succeeded in isolating a novel regulator of root growth by exploiting natural genetic variation in the model plant Arabidopsis. Quantitative trait locus analysis of a cross between isogenized accessions revealed that a single locus is responsible for approximately 80% of the variance of the observed difference in root length. This gene, named BREVIS RADIX (BRX), controls the extent of cell proliferation and elongation in the growth zone of the root tip. We isolated BRX by positional cloning. BRX is a member of a small group of highly conserved genes, the BRX gene family, which is only found in multicellular plants. Analyses of Arabidopsis single and double mutants suggest that BRX is the only gene of this family with a role in root development. The BRX protein is nuclear localized and activates transcription in a heterologous yeast system, indicating that BRX family proteins represent a novel class of transcription factors. Thus, we have identified a novel regulatory factor controlling quantitative aspects of root growth.}, } @article {pmid15028297, year = {2004}, author = {Cetkovic, H and Müller, WE and Gamulin, V}, title = {Bruton tyrosine kinase-like protein, BtkSD, is present in the marine sponge Suberites domuncula.}, journal = {Genomics}, volume = {83}, number = {4}, pages = {743-745}, doi = {10.1016/j.ygeno.2003.09.010}, pmid = {15028297}, issn = {0888-7543}, mesh = {Agammaglobulinaemia Tyrosine Kinase ; Amino Acid Sequence ; Animals ; Caenorhabditis elegans ; DNA, Complementary/metabolism ; Humans ; Molecular Sequence Data ; Mutation ; Porifera ; Protein-Tyrosine Kinases/*biosynthesis/*chemistry ; Sequence Homology, Amino Acid ; }, abstract = {Sponges, the simplest and most ancient phylum of Metazoa, encode in their genome complex and highly sophisticated proteins that evolved together with multicellularity and are found only in metazoan animals. We report here the finding of a Bruton tyrosine kinase (BTK)-like protein in the marine sponge Suberites domuncula (Demospongiae). The nucleotide sequence of one sponge cDNA predicts a 700-aa-long protein, which contains all of the characteristic domains for the Tec family of protein tyrosine kinases (PTKs). The highest homology (38% identity, 55% overall similarity) was found with human BTK and TEC PTKs. Sponge PTK was therefore named BtkSD. Human BTK is involved in the maturation of B cells and mutations in the BTK gene cause X-linked agammaglobulinemia. Kinases from the Tec family are not present in Caenorhabditis elegans and, until now, they were found only in insects and higher animal taxa. Our finding implies that the BTK/TEC genes are of a very ancient origin.}, } @article {pmid15024409, year = {2004}, author = {Xie, Z and Johansen, LK and Gustafson, AM and Kasschau, KD and Lellis, AD and Zilberman, D and Jacobsen, SE and Carrington, JC}, title = {Genetic and functional diversification of small RNA pathways in plants.}, journal = {PLoS biology}, volume = {2}, number = {5}, pages = {E104}, pmid = {15024409}, issn = {1545-7885}, support = {R37 GM060398/GM/NIGMS NIH HHS/United States ; R37 AI043288/AI/NIAID NIH HHS/United States ; R21 AI043288/AI/NIAID NIH HHS/United States ; R01 GM060398/GM/NIGMS NIH HHS/United States ; R01 AI043288/AI/NIAID NIH HHS/United States ; GM60398/GM/NIGMS NIH HHS/United States ; AI43288/AI/NIAID NIH HHS/United States ; F32A1051097//PHS HHS/United States ; }, mesh = {Arabidopsis/genetics ; Chromatin/chemistry ; Cytosine/chemistry ; DNA Methylation ; Evolution, Molecular ; Exons ; Genes, Plant ; Green Fluorescent Proteins/chemistry ; Heterochromatin/chemistry ; Histones/chemistry ; Immunoblotting ; Introns ; Methylation ; MicroRNAs/*chemistry ; Models, Genetic ; Molecular Sequence Data ; Mutation ; Plants/virology ; RNA/chemistry ; RNA, Small Interfering/*chemistry/metabolism ; RNA, Viral/genetics ; RNA-Dependent RNA Polymerase/chemistry ; Recombinant Fusion Proteins/chemistry ; Software ; }, abstract = {Multicellular eukaryotes produce small RNA molecules (approximately 21-24 nucleotides) of two general types, microRNA (miRNA) and short interfering RNA (siRNA). They collectively function as sequence-specific guides to silence or regulate genes, transposons, and viruses and to modify chromatin and genome structure. Formation or activity of small RNAs requires factors belonging to gene families that encode DICER (or DICER-LIKE [DCL]) and ARGONAUTE proteins and, in the case of some siRNAs, RNA-dependent RNA polymerase (RDR) proteins. Unlike many animals, plants encode multiple DCL and RDR proteins. Using a series of insertion mutants of Arabidopsis thaliana, unique functions for three DCL proteins in miRNA (DCL1), endogenous siRNA (DCL3), and viral siRNA (DCL2) biogenesis were identified. One RDR protein (RDR2) was required for all endogenous siRNAs analyzed. The loss of endogenous siRNA in dcl3 and rdr2 mutants was associated with loss of heterochromatic marks and increased transcript accumulation at some loci. Defects in siRNA-generation activity in response to turnip crinkle virus in dcl2 mutant plants correlated with increased virus susceptibility. We conclude that proliferation and diversification of DCL and RDR genes during evolution of plants contributed to specialization of small RNA-directed pathways for development, chromatin structure, and defense.}, } @article {pmid15013766, year = {2004}, author = {Khoei, S and Goliaei, B and Neshasteh-Riz, A and Deizadji, A}, title = {The role of heat shock protein 70 in the thermoresistance of prostate cancer cell line spheroids.}, journal = {FEBS letters}, volume = {561}, number = {1-3}, pages = {144-148}, doi = {10.1016/S0014-5793(04)00158-9}, pmid = {15013766}, issn = {0014-5793}, mesh = {Cell Line, Tumor ; Cell Survival ; *Fever ; HSP70 Heat-Shock Proteins/analysis/*biosynthesis/*physiology ; Hot Temperature ; Humans ; Kinetics ; Male ; Neoplastic Stem Cells ; Prostatic Neoplasms/metabolism/*pathology ; Spheroids, Cellular/*pathology ; }, abstract = {Heat shock protein 70 (Hsp70), a protein induced in cells exposed to sublethal heat shock, is present in all living cells and has been highly conserved during evolution. The aim of the current study was to determine the role of heat shock proteins in the resistance of prostate carcinoma cell line spheroids to hyperthermia. In vitro, the expression of Hsp70 by the DU 145 cell line, when cultured as monolayer or multicellular spheroids, was studied using Western blotting and enzyme-linked immunosorbent assay methods. The level of Hsp70 in spheroid cultures for up to 26 days at 37 degrees C remained similar to monolayer cultures. However, in samples treated with hyperthermia at 43 degrees C for 120 min, the spheroid cultures expressed a higher level of Hsp70 as compared to monolayer culture. Under similar conditions of heat treatment, the spheroids showed more heat resistance than monolayer cultures as judged by the number of colonies that they formed in suspension cultures. The results suggest that cells cultured in multicellular spheroids showed more heat resistance as compared to monolayer cultures by producing higher levels of Hsp70.}, } @article {pmid15009123, year = {2004}, author = {Cerra, A and Byrne, M}, title = {Evolution of development in the sea star genus Patiriella: clade-specific alterations in cleavage.}, journal = {Evolution & development}, volume = {6}, number = {2}, pages = {105-113}, doi = {10.1111/j.1525-142x.2004.04015.x}, pmid = {15009123}, issn = {1520-541X}, mesh = {Animals ; Australia ; *Biological Evolution ; Cell Division/physiology ; Cleavage Stage, Ovum/*physiology/ultrastructure ; Microscopy, Electron, Scanning ; Mitosis/physiology ; Species Specificity ; Starfish/*embryology ; }, abstract = {Examination of early development in five species of the Patiriella sea star species complex indicates that the ancestral-type radial holoblastic cleavage (Type I) is characteristic of P. regularis and P. exigua, whereas cleavage in species from the calcar clade followed multiple alternatives (Types II-IV) from holoblastic to meroblastic. Considering that invariant radial cleavage is thought to play a role in embryonic axis formation in echinoderms, we documented the details of blastomere formation in Patiriella sp. and followed development of the embryos. In Type II cleavage, the first and second cleavage planes appeared simultaneously at one pole of the embryo, dividing it directly into four equally sized blastomeres. In Type III cleavage, the first and second cleavage planes appeared simultaneously, followed promptly by the third cleavage plane, dividing the embryo directly into eight equally sized blastomeres. In Type IV cleavage, numerous furrows appeared simultaneously at one end of the embryo, dividing it into 32-40 equally sized blastomeres. Confocal sections revealed that embryos with cleavage Types II-IV were initially syncytial. The timing of karyokinesis in embryos with Types II and III cleavage was similar to that seen in clutch mates with Type I cleavage. Karyokinesis in embryos with Type IV cleavage, however, differed in timing compared with Type I clutch mates. Alteration in cleavage was not associated with polarized distribution of maternally provided nutrients. For each cleavage type, development was normal to the competent larval stage. Although variable blastomere configuration in the calcar clade may be linked to possession of a lecithotrophic development, other Patiriella species with this mode of development have typical cleavage. The presence of variable cleavage in all calcar clade species indicates that phylogenetic history has played a role in the distribution of this embryonic trait in Patiriella. The plasticity in early cleavage in these sea stars indicates that this aspect of early development is not constrained against change and that there are many ways to achieve multicellularity.}, } @article {pmid15005799, year = {2004}, author = {Hedges, SB and Blair, JE and Venturi, ML and Shoe, JL}, title = {A molecular timescale of eukaryote evolution and the rise of complex multicellular life.}, journal = {BMC evolutionary biology}, volume = {4}, number = {}, pages = {2}, pmid = {15005799}, issn = {1471-2148}, mesh = {Animals ; Eukaryotic Cells/*metabolism ; *Evolution, Molecular ; Fungi/genetics ; Genetic Variation ; Phylogeny ; Plants/genetics ; Proteins/genetics ; Rhodophyta/genetics ; Time Factors ; Vertebrates/genetics ; }, abstract = {BACKGROUND: The pattern and timing of the rise in complex multicellular life during Earth's history has not been established. Great disparity persists between the pattern suggested by the fossil record and that estimated by molecular clocks, especially for plants, animals, fungi, and the deepest branches of the eukaryote tree. Here, we used all available protein sequence data and molecular clock methods to place constraints on the increase in complexity through time.

RESULTS: Our phylogenetic analyses revealed that (i) animals are more closely related to fungi than to plants, (ii) red algae are closer to plants than to animals or fungi, (iii) choanoflagellates are closer to animals than to fungi or plants, (iv) diplomonads, euglenozoans, and alveolates each are basal to plants+animals+fungi, and (v) diplomonads are basal to other eukaryotes (including alveolates and euglenozoans). Divergence times were estimated from global and local clock methods using 20-188 proteins per node, with data treated separately (multigene) and concatenated (supergene). Different time estimation methods yielded similar results (within 5%): vertebrate-arthropod (964 million years ago, Ma), Cnidaria-Bilateria (1,298 Ma), Porifera-Eumetozoa (1,351 Ma), Pyrenomycetes-Plectomycetes (551 Ma), Candida-Saccharomyces (723 Ma), Hemiascomycetes-filamentous Ascomycota (982 Ma), Basidiomycota-Ascomycota (968 Ma), Mucorales-Basidiomycota (947 Ma), Fungi-Animalia (1,513 Ma), mosses-vascular plants (707 Ma), Chlorophyta-Tracheophyta (968 Ma), Rhodophyta-Chlorophyta+Embryophyta (1,428 Ma), Plantae-Animalia (1,609 Ma), Alveolata-plants+animals+fungi (1,973 Ma), Euglenozoa-plants+animals+fungi (1,961 Ma), and Giardia-plants+animals+fungi (2,309 Ma). By extrapolation, mitochondria arose approximately 2300-1800 Ma and plastids arose 1600-1500 Ma. Estimates of the maximum number of cell types of common ancestors, combined with divergence times, showed an increase from two cell types at 2500 Ma to approximately 10 types at 1500 Ma and 50 cell types at approximately 1000 Ma.

CONCLUSIONS: The results suggest that oxygen levels in the environment, and the ability of eukaryotes to extract energy from oxygen, as well as produce oxygen, were key factors in the rise of complex multicellular life. Mitochondria and organisms with more than 2-3 cell types appeared soon after the initial increase in oxygen levels at 2300 Ma. The addition of plastids at 1500 Ma, allowing eukaryotes to produce oxygen, preceded the major rise in complexity.}, } @article {pmid15005568, year = {2004}, author = {Seipel, K and Yanze, N and Schmid, V}, title = {The germ line and somatic stem cell gene Cniwi in the jellyfish Podocoryne carnea.}, journal = {The International journal of developmental biology}, volume = {48}, number = {1}, pages = {1-7}, doi = {10.1387/ijdb.15005568}, pmid = {15005568}, issn = {0214-6282}, mesh = {Aging/genetics ; Amino Acid Sequence ; Animals ; Cell Differentiation ; Cell Division ; Cloning, Molecular ; Gene Expression Regulation, Developmental ; Germ Cells/*metabolism ; Hydrozoa/*cytology/*genetics/growth & development ; Larva/genetics ; Molecular Sequence Data ; Phylogeny ; Proteins/*genetics ; RNA, Messenger/genetics/metabolism ; Sequence Alignment ; Stem Cells/*metabolism ; }, abstract = {In most animal phyla from insects to mammals, there is a clear division of somatic and germ line cells. This is however not the case in plants and some animal phyla including tunicates, flatworms and the basal phylum Cnidaria, where germ stem cells arise de novo from somatic cells. Piwi-like genes represent essential stem cell genes in diverse multicellular organisms. The cnidarian Piwihomolog Cniwiwas cloned from Podocoryne carnea, a hydrozoan with a full life cycle. CniwiRNA is present in all developmental stages with highest levels in the egg and the medusa. In the adult medusa, Cniwi expression is prominent in the gonads where it likely functions as a germ stem cell gene. The gene is also expressed, albeit at low levels, in differentiated somatic cells like the striated muscle of the medusa. Isolated striated muscle cells can be induced to transdifferentiate into smooth muscle cells which proliferate and differentiate into nerve cells. Cniwi expression is upregulated transiently after induction of transdifferentiation and again when the emerging smooth muscle cells proliferate and differentiate. The continuous low-level expression of an inducible stem cell gene in differentiated somatic cells may underlie the ability to form medusa buds from polyp cells and explain the extraordinary transdifferentation and regeneration potential of Podocoryne carnea.}, } @article {pmid15002569, year = {2002}, author = {Grimm, D and Kossmehl, P and Shakibaei, M and Schulze-Tanzil, G and Pickenhahn, H and Bauer, J and Paul, M and Cogoli, A}, title = {Effects of simulated microgravity on thyroid carcinoma cells.}, journal = {Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology}, volume = {9}, number = {1}, pages = {P253-6}, pmid = {15002569}, issn = {1077-9248}, abstract = {We aimed to investigate whether simulated microgravity on thyroid carcinoma cells could help to perform in vitro cancer studies such as antitumor drug tests more reliable and to spare animal experiments. We cultured cancer cells at 0 g to enable formation of three-dimensional multicellular tumor spheroids (MCTS), which will resemble the originating tumors. Under microgravity human follicular cells (ML-1 cell line) keep floating with-out stirring so that initial cell-cell interactions required for spheroid formation will be induced by forces due to biochemical components actually expressed on surfaces of cells, whereas gravity related push- or shear events will not influence MCTS formation. Within 12 hours of clinorotation the monolayer turned spontaneously into MCTS with remarkable features: An increase of extracellular matrix proteins and TGF-beta 1. Thyroglobulin, ft3 and ft4 secretion were markedly reduced. These data are in agreement with the observation that astronauts show low thyroid hormone levels after spaceflight.}, } @article {pmid14994649, year = {2003}, author = {Zlender, V}, title = {[Apoptosis--programmed cell death].}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {54}, number = {4}, pages = {267-274}, pmid = {14994649}, issn = {0004-1254}, mesh = {Apoptosis/*physiology ; }, abstract = {During the evolution, multi-cellular organisms have developed various protective mechanisms against environmental insults. Apoptosis is one of physiological mechanisms where in fact a cell itself actively induces its own death. In contrast to necrosis where the cell death occurs usually as a result of severe physical or chemical extra cellular factors accompanied by inflammatory reactions of tissue, the apoptotic process starts without signs and symptoms of inflammation, and generally starts from the inside of the cell, involving the use of energy and active synthesis of specific proteins. Apoptosis is important for the right balance between the loss of old, non-functional cells and the formation of new ones in certain organs and tissues. In addition, it is a specific answer of an organism to a number of pathological conditions. Thus apoptosis plays a very important role both in physiologic and pathologic processes in the body throughout the life of an organism. A normal development of embryo and foetus is impossible without a very intensive apoptotic process. The dysfunction of the apoptotic mechanism is associated with a number of diseases in humans and animals. The apoptosis starts by triggering different intra- and intercellular signals and stimulations, which involve a number of extrinsic or intrinsic apoptotic pathways resulting in caspase cascade activation. Caspases belongs to the family of cisteine proteases, and have a central role in facilitating a number of morphological and biochemical changes during the programmed cell death. The understanding of these complex pathways offers new approaches to clinical treatment of fatal human diseases. The promising possibilities of application of the knowledge about the mechanism of apoptosis in the treatment of human diseases make the research in this field challenging and exciting.}, } @article {pmid14989145, year = {2003}, author = {Jablonka, E and Lamb, MJ}, title = {[Epigenetic heredity in evolution].}, journal = {Tsitologiia}, volume = {45}, number = {11}, pages = {1057-1072}, pmid = {14989145}, issn = {0041-3771}, mesh = {Animals ; *Biological Evolution ; *Epigenesis, Genetic ; Heredity/*genetics ; }, abstract = {We discuss the role of cell memory in heredity and evolution. We describe the properties of the epigenetic inheritance systems (EISs) that underlie cell memory and enable environmentally and developmentally induced cell phenotypes to be transmitted in cell lineages, and argue that transgenerational epigenetic inheritance is an important and neglected part of heredity. By looking at the part EISs have played in the evolution of multicellularity, ontogeny, chromosome organization, and the origin of some post-mating isolating mechanisms, we show how considering the role of epigenetic inheritance can sometimes shed light on major evolutionary processes.}, } @article {pmid14987989, year = {2004}, author = {Piskur, J and Sandrini, MP and Knecht, W and Munch-Petersen, B}, title = {Animal deoxyribonucleoside kinases: 'forward' and 'retrograde' evolution of their substrate specificity.}, journal = {FEBS letters}, volume = {560}, number = {1-3}, pages = {3-6}, doi = {10.1016/S0014-5793(04)00081-X}, pmid = {14987989}, issn = {0014-5793}, mesh = {Amino Acid Sequence ; Animals ; Conserved Sequence ; DNA/chemistry ; *Evolution, Molecular ; Molecular Sequence Data ; Nucleic Acid Precursors/chemistry ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor)/*chemistry/*genetics/metabolism ; Phylogeny ; Point Mutation ; Sequence Homology, Amino Acid ; Structure-Activity Relationship ; Substrate Specificity ; }, abstract = {Deoxyribonucleoside kinases, which catalyse the phosphorylation of deoxyribonucleosides, are present in several copies in most multicellular organisms and therefore represent an excellent model to study gene duplication and specialisation of the duplicated copies through partitioning of substrate specificity. Recent studies suggest that in the animal lineage one of the progenitor kinases, the so-called dCK/dGK/TK2-like gene, was duplicated prior to separation of the insect and mammalian lineages. Thereafter, insects lost all but one kinase, dNK (EC 2.7.1.145), which subsequently, through remodelling of a limited number of amino acid residues, gained a broad substrate specificity.}, } @article {pmid14986094, year = {2004}, author = {Savidge, WB and Blair, NE}, title = {Patterns of intramolecular carbon isotopic heterogeneity within amino acids of autotrophs and heterotrophs.}, journal = {Oecologia}, volume = {139}, number = {2}, pages = {178-189}, pmid = {14986094}, issn = {0029-8549}, mesh = {Amino Acids/*chemistry ; Animals ; Carbon/analysis/*chemistry ; Carbon Isotopes/analysis ; Eukaryota ; Invertebrates ; *Models, Theoretical ; Poaceae ; }, abstract = {A survey of the intramolecular C isotopic composition of a variety of organisms was conducted to investigate the potential of intramolecular isotopic measurements as a tracer of biological or geochemical processes. Based on a consideration of inorganic C sources and enzymatic fractionations, contrasting predictions were made for the relative (13)C enrichments of the alpha-carboxyl carbons fixed by the anapleurotic (beta)-carboxylation pathway during amino acid synthesis by photoautotrophs and heterotrophs. To test the model predictions, the stable C isotopic compositions of the acid hydrolyzable C fraction, the total amino acid alpha-carboxyl C fraction and the alpha-carboxyl C of glutamate from a variety of autotrophic and heterotrophic organisms were compared. The relative (13)C enrichments of carboxyl carbons in the bulk amino acid fraction and in glutamate conformed qualitatively to model predictions. Macroalgal taxa possessed a significantly less enriched carboxyl C fraction than did either C3 or C4 vascular plants, indicating the presence of a different beta-carboxylation pathway operating in these organisms. In most multicellular heterotrophs, the isotopic composition of the amino acid carboxyl carbons closely resembled that of their food sources. Amino acids are apparently assimilated into tissue proteins directly from their diets without significant metabolic modification. However, shifts in the isotopic composition of the carboxyl C fractions in some organisms were detected that were consistent with the occurrence of significant resynthesis of amino acids from non-amino acid precursors. Comparison of plant leaves and roots provided evidence of environmentally controlled assimilate partitioning. Intramolecular isotopic measurements of biological molecules provide unique insights into the origins and transformations of bio-molecules.}, } @article {pmid14984742, year = {2004}, author = {Hazkani-Covo, E and Levanon, EY and Rotman, G and Graur, D and Novik, A}, title = {Evolution of multicellularity in Metazoa: comparative analysis of the subcellular localization of proteins in Saccharomyces, Drosophila and Caenorhabditis.}, journal = {Cell biology international}, volume = {28}, number = {3}, pages = {171-178}, doi = {10.1016/j.cellbi.2003.11.016}, pmid = {14984742}, issn = {1065-6995}, mesh = {Animals ; *Biological Evolution ; Caenorhabditis elegans/*metabolism ; Caenorhabditis elegans Proteins/*metabolism ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/*metabolism ; Organelles/metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {A comparison of the subcellular assignments of proteins between the unicellular Saccharomyces cerevisiae and the multicellular Drosophila melanogaster and Caenorhabditis elegans was performed using a computational tool for the prediction of subcellular localization. Nine subcellular compartments were studied: (1) extracellular domain, (2) cell membrane, (3) cytoplasm, (4) endoplasmic reticulum, (5) Golgi apparatus, (6) lysosome, (7) peroxisome, (8) mitochondria, and (9) nucleus. The transition to multicellularity was found to be characterized by an increase in the total number of proteins encoded by the genome. Interestingly, this increase is distributed unevenly among the subcellular compartments. That is, a disproportionate increase in the number of proteins in the extracellular domain, the cell membrane, and the cytoplasm is observed in multicellular organisms, while no such increase is seen in other subcellular compartments. A possible explanation involves signal transduction. In terms of protein numbers, signal transduction pathways may be roughly described as a pyramid with an expansive base in the extracellular domain (the numerous extracellular signal proteins), progressively narrowing at the cell membrane and cytoplasmic levels, and ending in a narrow tip consisting of only a handful of transcription modulators in the nucleus. Our observations suggest that extracellular signaling interactions among metazoan cells account for the uneven increase in the numbers of proteins among subcellular compartments during the transition to multicellularity.}, } @article {pmid14981244, year = {2004}, author = {Jakab, K and Neagu, A and Mironov, V and Markwald, RR and Forgacs, G}, title = {Engineering biological structures of prescribed shape using self-assembling multicellular systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {101}, number = {9}, pages = {2864-2869}, pmid = {14981244}, issn = {0027-8424}, mesh = {Animals ; CHO Cells ; Cell Aggregation/*physiology ; Cell Fusion ; Cell Size/*physiology ; Computer Simulation ; Cricetinae ; Models, Biological ; }, abstract = {Self-assembly is a fundamental process that drives structural organization in both inanimate and living systems. It is in the course of self-assembly of cells and tissues in early development that the organism and its parts eventually acquire their final shape. Even though developmental patterning through self-assembly is under strict genetic control it is clear that ultimately it is physical mechanisms that bring about the complex structures. Here we show, both experimentally and by using computer simulations, how tissue liquidity can be used to build tissue constructs of prescribed geometry in vitro. Spherical aggregates containing many thousands of cells, which form because of tissue liquidity, were implanted contiguously into biocompatible hydrogels in circular geometry. Depending on the properties of the gel, upon incubation, the aggregates either fused into a toroidal 3D structure or their constituent cells dispersed into the surrounding matrix. The model simulations, which reproduced the experimentally observed shapes, indicate that the control parameter of structure evolution is the aggregate-gel interfacial tension. The model-based analysis also revealed that the observed toroidal structure represents a metastable state of the cellular system, whose lifetime depends on the magnitude of cell-cell and cell-matrix interactions. Thus, these constructs can be made long-lived. We suggest that spherical aggregates composed of organ-specific cells may be used as "bio-ink" in the evolving technology of organ printing.}, } @article {pmid14973485, year = {2004}, author = {Pawlowska, TE and Taylor, JW}, title = {Organization of genetic variation in individuals of arbuscular mycorrhizal fungi.}, journal = {Nature}, volume = {427}, number = {6976}, pages = {733-737}, doi = {10.1038/nature02290}, pmid = {14973485}, issn = {1476-4687}, mesh = {Cell Nucleus/*genetics ; DNA, Plant/genetics ; DNA, Ribosomal/genetics ; Evolution, Molecular ; Fungi/*cytology/*genetics/physiology ; *Genetic Variation ; Genome, Fungal ; *Models, Genetic ; Molecular Sequence Data ; Plants/microbiology ; Polymorphism, Genetic/genetics ; Recombination, Genetic/genetics ; Reproduction, Asexual/*genetics ; Spores, Fungal/cytology/genetics ; }, abstract = {Arbuscular mycorrhizal (AM) fungi (Glomeromycota) are thought to be the oldest group of asexual multicellular organisms. They colonize the roots of most land plants, where they facilitate mineral uptake from the soil in exchange for plant-assimilated carbon. Cells of AM fungi contain hundreds of nuclei. Unusual polymorphism of ribosomal DNA observed in individual spores of AM fungi inspired a hypothesis that heterokaryosis--that is, the coexistence of many dissimilar nuclei in cells--occurs throughout the AM fungal life history. Here we report a genetic approach to test the hypothesis of heterokaryosis in AM fungi. Our study of the transmission of polymorphic genetic markers in natural isolates of Glomus etunicatum, coupled with direct amplification of rDNA from microdissected nuclei by polymerase chain reaction, supports the alternative hypothesis of homokaryosis, in which nuclei populating AM fungal individuals are genetically uniform. Intrasporal rDNA polymorphism contained in each nucleus signals a relaxation of concerted evolution, a recombination-driven process that is responsible for homogenizing rDNA repeats. Polyploid organization of glomeromycotan genomes could accommodate intranuclear rDNA polymorphism and buffer these apparently asexual organisms against the effects of accumulating mutations.}, } @article {pmid14760914, year = {2003}, author = {Garny, A and Kohl, P and Hunter, PJ and Boyett, MR and Noble, D}, title = {One-dimensional rabbit sinoatrial node models: benefits and limitations.}, journal = {Journal of cardiovascular electrophysiology}, volume = {14}, number = {10 Suppl}, pages = {S121-32}, doi = {10.1046/j.1540.8167.90301.x}, pmid = {14760914}, issn = {1045-3873}, mesh = {Action Potentials/physiology ; Algorithms ; Animals ; Computer Simulation ; Electric Conductivity ; Electrophysiology ; Gap Junctions/physiology ; Heart Atria ; Models, Biological ; Pacemaker, Artificial ; Rabbits ; Sinoatrial Node/cytology/*physiology ; }, abstract = {INTRODUCTION: Cardiac multicellular modeling has traditionally focused on ventricular electromechanics. More recently, models of the atria have started to emerge, and there is much interest in addressing sinoatrial node structure and function.

METHODS AND RESULTS: We implemented a variety of one-dimensional sinoatrial models consisting of descriptions of central, transitional, and peripheral sinoatrial node cells, as well as rabbit or human atrial cells. These one-dimensional models were implemented using CMISS on an SGI Origin 2000 supercomputer. Intercellular coupling parameters recorded in experimental studies on sinoatrial node and atrial cell-pairs under-represent the electrotonic interactions that any cardiomyocyte would have in a multidimensional setting. Unsurprisingly, cell-to-cell coupling had to be scaled-up (by a factor of 5) in order to obtain a stable leading pacemaker site in the sinoatrial node center. Further critical parameters include the gradual increase in intercellular coupling from sinoatrial node center to periphery, and the presence of electrotonic interaction with atrial cells. Interestingly, the electrotonic effect of the atrium on sinoatrial node periphery is best described as opposing depolarization, rather than necessarily hyperpolarizing, as often assumed.

CONCLUSION: Multicellular one-dimensional models of sinoatrial node and atrium can provide useful insight into the origin and spread of normal cardiac excitation. They require larger than "physiologic" intercellular conductivities in order to make up for a lack of "anatomical" spatial scaling. Multicellular models for more in-depth quantitative studies will require more realistic anatomico-physiologic properties.}, } @article {pmid14756344, year = {2003}, author = {Solé, RV and Fernández, P and Kauffman, SA}, title = {Adaptive walks in a gene network model of morphogenesis: insights into the Cambrian explosion.}, journal = {The International journal of developmental biology}, volume = {47}, number = {7-8}, pages = {685-693}, pmid = {14756344}, issn = {0214-6282}, mesh = {*Adaptation, Physiological ; Algorithms ; Animals ; Cell Communication ; Computer Simulation ; Evolution, Molecular ; *Fossils ; Gene Expression Regulation, Developmental ; Genes, Regulator ; Genetic Variation ; Genetics, Population ; Kinetics ; Models, Theoretical ; *Morphogenesis ; Multigene Family ; }, abstract = {The emergence of complex patterns of organization close to the Cambrian boundary is known to have happened over a (geologically) short period of time. It involved the rapid diversification of body plans and stands as one of the major transitions in evolution. How it took place is a controversial issue. Here we explore this problem by considering a simple model of pattern formation in multicellular organisms. By modeling gene network-based morphogenesis and its evolution through adaptive walks, we explore the question of how combinatorial explosions might have been actually involved in the Cambrian event. Here we show that a small amount of genetic complexity including both gene regulation and cell-cell signaling allows one to generate an extraordinary repertoire of stable spatial patterns of gene expression compatible with observed anteroposterior patterns in early development of metazoans. The consequences for the understanding of the tempo and mode of the Cambrian event are outlined.}, } @article {pmid14755074, year = {2004}, author = {Wilson, MS and Maizels, RM}, title = {Regulation of allergy and autoimmunity in helminth infection.}, journal = {Clinical reviews in allergy & immunology}, volume = {26}, number = {1}, pages = {35-50}, pmid = {14755074}, issn = {1080-0549}, mesh = {Animals ; Autoimmune Diseases/*prevention & control ; Autoimmunity ; Helminthiasis/*immunology/parasitology/physiopathology ; Host-Parasite Interactions ; Humans ; Hygiene ; Hypersensitivity/*prevention & control ; Models, Immunological ; }, abstract = {Parasitic infections are a major theme in the "hygiene hypothesis", as allergies and autoimmune diseases are less prevalent in countries with higher burdens of helminths and other parasitic organisms. Helminths"-the grouping of multicellular worm parasites including nematodes, cestodes and trematodes-tend to establish long-lived, chronic infections indicating successful down-modulation of the host immune system. In this review, we describe the intricate immunology of host-helminth interactions and how parasites manipulate immune responses to enhance their survival. In so doing, they often minimise immunopathology and, it is suggested, reduce host susceptibility to, and severity of allergic and autoimmune diseases. Studies on helminth-infected communities and individuals support the hypothesis that an immuno-regulatory network promoted by parasites extends its influence to limiting allergies. Experimental models are now probing more deeply into the area of immune modulation by helminths, and we discuss the likely mechanisms by which helminths could be establishing a strongly regulatory environment. Understanding and harnessing the modulatory capacity of helminths may uncover novel therapeutic interventions, mimicking and exploiting their evolution for our benefit. Parasitic infections are a major theme in the "hygiene hypothesis", as allergies and autoimmune diseases are less prevalent in countries with higher burdens of helminths and other parasitic organisms. Helminths"-the grouping of multicellular worm parasites including nematodes, cestodes and trematodes-tend to establish long-lived, chronic infections indicating successful down-modulation of the host immune system. In this review, we describe the intricate immunology of host-helminth interactions and how parasites manipulate immune responses to enhance their survival. In so doing, they often minimise immunopathology and, it is suggested, reduce host susceptibility to, and severity of allergic and autoimmune diseases. Studies on helminth-infected communities and individuals support the hypothesis that an immuno-regulatory network promoted by parasites extends its influence to limiting allergies. Experimental models are now probing more deeply into the area of immune modulation by helminths, and we discuss the likely mechanisms by which helminths could be establishing a strongly regulatory environment. Understanding and harnessing the modulatory capacity of helminths may uncover novel therapeutic interventions, mimicking and exploiting their evolution for our benefit.}, } @article {pmid14739244, year = {2004}, author = {Lake, JA and Rivera, MC}, title = {Deriving the genomic tree of life in the presence of horizontal gene transfer: conditioned reconstruction.}, journal = {Molecular biology and evolution}, volume = {21}, number = {4}, pages = {681-690}, doi = {10.1093/molbev/msh061}, pmid = {14739244}, issn = {0737-4038}, mesh = {Computational Biology ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; Genome ; Genomics/*methods ; Sequence Alignment/methods ; }, abstract = {The horizontal gene transfer (HGT) being inferred within prokaryotic genomes appears to be sufficiently massive that many scientists think it may have effectively obscured much of the history of life recorded in DNA. Here, we demonstrate that the tree of life can be reconstructed even in the presence of extensive HGT, provided the processes of genome evolution are properly modeled. We show that the dynamic deletions and insertions of genes that occur during genome evolution, including those introduced by HGT, may be modeled using techniques similar to those used to model nucleotide substitutions that occur during sequence evolution. In particular, we show that appropriately designed general Markov models are reasonable tools for reconstructing genome evolution. These studies indicate that, provided genomes contain sufficiently many genes and that the Markov assumptions are met, it is possible to reconstruct the tree of life. We also consider the fusion of genomes, a process not encountered in gene sequence evolution, and derive a method for the identification and reconstruction of genome fusion events. Genomic reconstructions of a well-defined classical four-genome problem, the root of the multicellular animals, show that the method, when used in conjunction with paralinear/logdet distances, performs remarkably well and is relatively unaffected by the recently discovered big genome artifact.}, } @article {pmid14729283, year = {2004}, author = {Noto, T and Endoh, H}, title = {A "chimera" theory on the origin of dicyemid mesozoans: evolution driven by frequent lateral gene transfer from host to parasite.}, journal = {Bio Systems}, volume = {73}, number = {1}, pages = {73-83}, doi = {10.1016/j.biosystems.2003.09.002}, pmid = {14729283}, issn = {0303-2647}, mesh = {Animals ; Chimera/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Host-Parasite Interactions/*genetics ; Invertebrates/genetics ; Nematoda/genetics ; }, abstract = {The phylogenetic status of the enigmatic dicyemid mesozoans is still uncertain. Are they primitive multicellular organisms or degenerate triploblastic animals? Presently, the latter view is accepted. A phylogenetic analysis of 18S rDNA sequences placed dicyemids within the animal clade, and this was supported by the discovery of a Hox-type gene with a lophotrochozoan signature sequence. This molecular information suggests that dicyemid mesozoans evolved from an ancestral animal degenerately. Considering their extreme simplicity, which is probably due to parasitism, they might have come from an early embryo via a radical transformation, i.e. neoteny. Irrespective of this molecular information, dicyemid mesozoans retain many protistan-like or extremely primitive features, such as tubular mitochondrial cristae, endocytic ability from the outer surface, and the absence of collagenous tissue, while they do not share noticeable synapomorphy with animals. In addition, the 5S rRNA phylogeny suggests a somewhat closer kinship with protozoan ciliates than with animals. If we accept this clear contradiction, dicyemids should be regarded as a chimera of animals and protistans. Here, we discuss the traditional theory of extreme degeneration via parasitism, and then propose a new "chimera" theory in which dicyemid mesozoans are exposed to a continual flow of genetic information via eating host tissues from the outer surface by endocytosis. Consequently, many of their intrinsic genes have been replaced by host-derived genes through lateral gene transfer (LGT), implying that LGT is a key driving force in the evolution of dicyemid mesozoans.}, } @article {pmid14727109, year = {2004}, author = {Fedders, H and Augustin, R and Bosch, TC}, title = {A Dickkopf- 3-related gene is expressed in differentiating nematocytes in the basal metazoan Hydra.}, journal = {Development genes and evolution}, volume = {214}, number = {2}, pages = {72-80}, pmid = {14727109}, issn = {0949-944X}, mesh = {Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; Base Sequence ; Caenorhabditis elegans ; Chemokines ; Chickens ; Drosophila ; Embryo, Nonmammalian/embryology ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Humans ; Hydra/embryology/*genetics ; Intercellular Signaling Peptides and Proteins ; Mice ; Molecular Sequence Data ; Phylogeny ; Proteins/*genetics ; Sequence Alignment ; }, abstract = {In vertebrate development the Dickkopf protein family carries out multiple functions and is represented by at least four different genes with distinct biological activities. In invertebrates such as Drosophila and Caenorhabditis, Dickkopf genes have so far not been identified. Here we describe the identification and characterization of a Dickkopf gene with a deduced amino acid sequence closely related to that of chicken Dkk-3 in the basal metazoan Hydra. HyDkk-3 appears to be the only Dickkopf gene in Hydra. The gene is expressed in the gastric region in nematocytes at a late differentiation stage. In silico searches of EST and genome databases indicated the absence of Dkk genes from the protostomes Drosophila and Caenorhabditis, whereas within the deuterostomes, a Dkk-3 gene could be identified in the genome of the urochordate Ciona intestinalis. The results indicate that at an early stage of evolution of multicellularity Dickkopf proteins have already played important roles as developmental signals. They also suggest that vertebrate Dkk-1, 2 and 4 may have originated from a common ancestor gene of Dkk-3.}, } @article {pmid14719364, year = {2003}, author = {Baranowski, E and Ruiz-Jarabo, CM and Pariente, N and Verdaguer, N and Domingo, E}, title = {Evolution of cell recognition by viruses: a source of biological novelty with medical implications.}, journal = {Advances in virus research}, volume = {62}, number = {}, pages = {19-111}, pmid = {14719364}, issn = {0065-3527}, mesh = {Amino Acid Sequence ; Animals ; Biological Evolution ; Genetic Therapy ; Genetic Variation ; Humans ; Models, Molecular ; Protein Conformation ; Receptors, Virus/chemistry/*physiology ; Selection, Genetic ; Viral Proteins/chemistry/genetics/physiology ; Virus Diseases/virology ; Viruses/*genetics/*pathogenicity ; }, abstract = {The picture beginning to form from genome analyses of viruses, unicellular organisms, and multicellular organisms is that viruses have shared functional modules with cells. A process of coevolution has probably involved exchanges of genetic information between cells and viruses for long evolutionary periods. From this point of view present-day viruses show flexibility in receptor usage and a capacity to alter through mutation their receptor recognition specificity. It is possible that for the complex DNA viruses, due to a likely limited tolerance to generalized high mutation rates, modifications in receptor specificity will be less frequent than for RNA viruses, albeit with similar biological consequences once they occur. It is found that different receptors, or allelic forms of one receptor, may be used with different efficiency and receptor affinities are probably modified by mutation and selection. Receptor abundance and its affinity for a virus may modulate not only the efficiency of infection, but also the capacity of the virus to diffuse toward other sites of the organism. The chapter concludes that receptors may be shared by different, unrelated viruses and that one virus may use several receptors and may expand its receptor specificity in ways that, at present, are largely unpredictable.}, } @article {pmid14710996, year = {2004}, author = {Canning, EU and Okamura, B}, title = {Biodiversity and evolution of the Myxozoa.}, journal = {Advances in parasitology}, volume = {56}, number = {}, pages = {43-131}, doi = {10.1016/s0065-308x(03)56002-x}, pmid = {14710996}, issn = {0065-308X}, mesh = {Animals ; *Biodiversity ; *Biological Evolution ; Eukaryota/*physiology ; Parasites/*physiology ; }, abstract = {Myxozoans (phylum Myxozoa) are metazoan parasites utilizing invertebrate and (mainly) aquatic vertebrate hosts. They have in common with cnidarians the possession of virtually identical, highly complex organelles, namely the polar capsules in myxozoan spores, serving for attachment to new hosts and the nematocysts in surface epithelia of cnidarians, serving for food capture. Although myxozoan spores are multicellular, the simple trophic body forms of almost all species, reduced to syncytial plasmodia or single cells, reveal no clues to myxozoan ancestry or phylogenetic relationships. The myxozoan genus Buddenbrockia is one of only two known genera belonging to a clade which diverged early in the evolution of the Myxozoa. Today the Myxozoa are represented by two classes, the Myxosporea, containing all the better-known genera, which alternate between fish and annelids, and the Malacosporea, containing Buddenbrockia and Tetracapsuloides, parasitising bryozoans. The latter genus also infects salmonid fish, causing proliferative kidney disease (PKD). The enigmatic Buddenbrockia has retained some of its ancestral features in a body wall of two cell layers and a worm-like shape, maintained by four longitudinally-running muscle blocks, similar to a gutless nematode and suggestive of a bilaterian ancestry. Although some analyses of 18S rDNA sequences tend towards a cnidarian (diploblast) affinity for myxozoans, the majority of these studies place them within, or sister to, the Bilateria. The latter view is supported by their possession of central class Hox genes, so far considered to be synapomorphic for Bilateria. The simple body form is, therefore, an extreme example of simplification due to parasitism. Various hypotheses for the occurrence of identical complex organelles (nematocysts and polar capsules) in diploblast and triploblast phyla are evaluated: common ancestry, convergent evolution, gene transfer and, especially, endosymbiosis. A theory of the evolution of their digenetic life cycles is proposed, with the invertebrate as primary host and secondary acquisition of the vertebrate host serving for asexual population increase.}, } @article {pmid14704431, year = {2004}, author = {Li, S and Armstrong, CM and Bertin, N and Ge, H and Milstein, S and Boxem, M and Vidalain, PO and Han, JD and Chesneau, A and Hao, T and Goldberg, DS and Li, N and Martinez, M and Rual, JF and Lamesch, P and Xu, L and Tewari, M and Wong, SL and Zhang, LV and Berriz, GF and Jacotot, L and Vaglio, P and Reboul, J and Hirozane-Kishikawa, T and Li, Q and Gabel, HW and Elewa, A and Baumgartner, B and Rose, DJ and Yu, H and Bosak, S and Sequerra, R and Fraser, A and Mango, SE and Saxton, WM and Strome, S and Van Den Heuvel, S and Piano, F and Vandenhaute, J and Sardet, C and Gerstein, M and Doucette-Stamm, L and Gunsalus, KC and Harper, JW and Cusick, ME and Roth, FP and Hill, DE and Vidal, M}, title = {A map of the interactome network of the metazoan C. elegans.}, journal = {Science (New York, N.Y.)}, volume = {303}, number = {5657}, pages = {540-543}, pmid = {14704431}, issn = {1095-9203}, support = {R01 AG011085/AG/NIA NIH HHS/United States ; R01 GM034059/GM/NIGMS NIH HHS/United States ; R01 GM034059-18/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Computational Biology ; Evolution, Molecular ; Genes, Helminth ; Genomics ; Open Reading Frames ; Phenotype ; Protein Binding ; Proteome/*metabolism ; Transcription, Genetic ; Two-Hybrid System Techniques ; }, abstract = {To initiate studies on how protein-protein interaction (or "interactome") networks relate to multicellular functions, we have mapped a large fraction of the Caenorhabditis elegans interactome network. Starting with a subset of metazoan-specific proteins, more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens. Independent coaffinity purification assays experimentally validated the overall quality of this Y2H data set. Together with already described Y2H interactions and interologs predicted in silico, the current version of the Worm Interactome (WI5) map contains approximately 5500 interactions. Topological and biological features of this interactome network, as well as its integration with phenome and transcriptome data sets, lead to numerous biological hypotheses.}, } @article {pmid14694082, year = {2004}, author = {Johnson, KP}, title = {Deletion bias in avian introns over evolutionary timescales.}, journal = {Molecular biology and evolution}, volume = {21}, number = {3}, pages = {599-602}, doi = {10.1093/molbev/msh051}, pmid = {14694082}, issn = {0737-4038}, mesh = {Animals ; Birds/*genetics ; *Evolution, Molecular ; Fibrinogen/genetics ; *Introns ; Mutation ; Phylogeny ; Selection, Genetic ; *Sequence Deletion ; }, abstract = {The role that introns play in the function and evolution of nuclear genomes is not fully understood. Recent models of intron evolution suggest that selection and drift may interact to maintain introns in multicellular organisms. In addition, deletion mutations are more likely to become fixed than insertion mutations. Examination of indel substitutions over macroevolutionary timescales in pigeons and doves (Aves: Columbiformes) reveals that deletion substitutions outnumber insertion substitutions by over six times. The length of indel events is variable.}, } @article {pmid14693369, year = {2004}, author = {Xu, R and Ye, X and Quinn Li, Q}, title = {AtCPSF73-II gene encoding an Arabidopsis homolog of CPSF 73 kDa subunit is critical for early embryo development.}, journal = {Gene}, volume = {324}, number = {}, pages = {35-45}, doi = {10.1016/j.gene.2003.09.025}, pmid = {14693369}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Arabidopsis/*genetics/growth & development ; Arabidopsis Proteins/*genetics ; Base Sequence ; Cleavage And Polyadenylation Specificity Factor ; Cloning, Molecular ; DNA, Bacterial/genetics ; DNA, Complementary/chemistry/genetics ; Fertility/genetics ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Genes, Lethal/genetics ; Molecular Sequence Data ; Mutagenesis, Insertional ; Phenotype ; Phylogeny ; Seeds/*genetics/growth & development ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; }, abstract = {We have identified and genetically characterized an Arabidopsis thaliana gene encoding a homolog of the Cleavage and Polyadenylation Specificity Factor (CPSF). This gene, named AtCPSF73-II, has been found to have a critical role in development by loss-of-function analysis using a Dissociation (Ds) insertion line SGT1922. The homozygous SGT1922 plants were lethal, but the heterozygous plants, while retaining their normal vegetative growth, displayed empty seed spaces as well as aborted seeds with embryos arrested at the globular stage. Genetic analysis indicated that the disruption of the AtCPSF73-II gene in SGT1922 plants caused severe reduction in genetic transmission of female gametes due to a loss of fertility, while the transmission of male gametes was normal. Two independent heterozygous lines with T-DNA insertion on the AtCPSF73-II gene also showed the similar phenotype. Gene expression analysis demonstrated that AtCPSF73-II was preferentially expressed in flowers. Protein sequence analysis revealed a group of AtCPSF73-II homologs with unknown function in animals, but not in yeast, which suggested a potential important function of this group of genes in the development of multicellular organisms.}, } @article {pmid14667362, year = {2003}, author = {Nedelcu, AM and Michod, RE}, title = {Sex as a response to oxidative stress: the effect of antioxidants on sexual induction in a facultatively sexual lineage.}, journal = {Proceedings. Biological sciences}, volume = {270 Suppl 2}, number = {Suppl 2}, pages = {S136-9}, pmid = {14667362}, issn = {0962-8452}, mesh = {2,2'-Dipyridyl/pharmacology ; *Adaptation, Physiological ; Antioxidants/*pharmacology ; Apoptosis/physiology ; Catalase/pharmacology ; Cell Cycle/physiology ; Oxidative Stress/*physiology ; Reactive Oxygen Species/metabolism ; *Sex ; Volvox/drug effects/*physiology ; }, abstract = {The evolution of sex is one of the long-standing unsolved problems in biology. Although in many lineages sex is an obligatory part of the life cycle and is associated with reproduction, in prokaryotes and many lower eukaryotes, sex is facultative, occurs in response to stress and often involves the formation of a stress-resistant dormant form. The proximate and ultimate causes of the connection between stress and sex in facultatively sexual lineages are unclear. Because most forms of stress result in the overproduction of cellular reactive oxygen species (ROS), we address the hypothesis that this connection involves ROS and possibly reflects the ancestral role of sex as an adaptive response to the damaging effects of stress-induced ROS (i.e. oxidative stress). Here, we report that two antioxidants inhibit sexual induction in a facultatively sexual species - the multicellular green alga, Volvox carteri. Furthermore, the nature of the sex response and the effect of an iron chelator on sexual induction are consistent with sex being a response to the DNA-damaging effects of ROS. In addition, we present preliminary data to suggest that sex, cell-cycle arrest and apoptosis are alternative responses to increased levels of oxidative stress.}, } @article {pmid14662353, year = {2003}, author = {Webb, JS and Givskov, M and Kjelleberg, S}, title = {Bacterial biofilms: prokaryotic adventures in multicellularity.}, journal = {Current opinion in microbiology}, volume = {6}, number = {6}, pages = {578-585}, doi = {10.1016/j.mib.2003.10.014}, pmid = {14662353}, issn = {1369-5274}, mesh = {Bacteria/*growth & development ; Biofilms/*growth & development ; Biological Evolution ; }, abstract = {The development of bacterial biofilms includes both the initial social behavior of undifferentiated cells, as well as cell death and differentiation in the mature biofilm, and displays several striking similarities with higher organisms. Recent advances in the field provide new insight into differentiation and cell death events in bacterial biofilm development and propose that biofilms have an unexpected level of multicellularity.}, } @article {pmid14660383, year = {2003}, author = {Borucki, MK and Peppin, JD and White, D and Loge, F and Call, DR}, title = {Variation in biofilm formation among strains of Listeria monocytogenes.}, journal = {Applied and environmental microbiology}, volume = {69}, number = {12}, pages = {7336-7342}, pmid = {14660383}, issn = {0099-2240}, mesh = {Animals ; Bacteriological Techniques ; Biofilms/*growth & development ; Culture Media ; Humans ; Listeria monocytogenes/*classification/genetics/*growth & development/pathogenicity ; Microscopy, Electron, Scanning ; Milk/microbiology ; Phylogeny ; Polysaccharides, Bacterial/biosynthesis ; Polyvinyl Chloride ; Serotyping ; Stainless Steel ; }, abstract = {Contamination of food by Listeria monocytogenes is thought to occur most frequently in food-processing environments where cells persist due to their ability to attach to stainless steel and other surfaces. Once attached these cells may produce multicellular biofilms that are resistant to disinfection and from which cells can become detached and contaminate food products. Because there is a correlation between virulence and serotype (and thus phylogenetic division) of L. monocytogenes, it is important to determine if there is a link between biofilm formation and disease incidence for L. monocytogenes. Eighty L. monocytogenes isolates were screened for biofilm formation to determine if there is a robust relationship between biofilm formation, phylogenic division, and persistence in the environment. Statistically significant differences were detected between phylogenetic divisions. Increased biofilm formation was observed in Division II strains (serotypes 1/2a and 1/2c), which are not normally associated with food-borne outbreaks. Differences in biofilm formation were also detected between persistent and nonpersistent strains isolated from bulk milk samples, with persistent strains showing increased biofilm formation relative to nonpersistent strains. There were no significant differences detected among serotypes. Exopolysaccharide production correlated with cell adherence for high-biofilm-producing strains. Scanning electron microscopy showed that a high-biofilm-forming strain produced a dense, three-dimensional structure, whereas a low-biofilm-forming strain produced a thin, patchy biofilm. These data are consistent with data on persistent strains forming biofilms but do not support a consistent relationship between enhanced biofilm formation and disease incidence.}, } @article {pmid14657359, year = {2003}, author = {Nowak, MA and Michor, F and Iwasa, Y}, title = {The linear process of somatic evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {100}, number = {25}, pages = {14966-14969}, pmid = {14657359}, issn = {0027-8424}, mesh = {Animals ; Apoptosis ; *Biological Evolution ; Genes, Tumor Suppressor ; Humans ; Models, Theoretical ; Mutation ; Neoplasms/genetics/pathology ; Phenotype ; }, abstract = {Cancer is the consequence of an unwanted evolutionary process. Cells receive mutations that alter their phenotype. Especially dangerous are those mutations that increase the net reproductive rate of cells, thereby leading to neoplasia and later to cancer. The standard models of evolutionary dynamics consider well mixed populations of individuals in symmetric positions. Here we introduce a spatially explicit, asymmetric stochastic process that captures the essential architecture of evolutionary dynamics operating within tissues of multicellular organisms. The "linear process" has the property of cancelling out selective differences among cells yet retaining the protective function of apoptosis. This design can slow down the rate of somatic evolution dramatically and therefore delay the onset of cancer.}, } @article {pmid14657113, year = {2003}, author = {Sekiguchi, Y and Yamada, T and Hanada, S and Ohashi, A and Harada, H and Kamagata, Y}, title = {Anaerolinea thermophila gen. nov., sp. nov. and Caldilinea aerophila gen. nov., sp. nov., novel filamentous thermophiles that represent a previously uncultured lineage of the domain Bacteria at the subphylum level.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {53}, number = {Pt 6}, pages = {1843-1851}, doi = {10.1099/ijs.0.02699-0}, pmid = {14657113}, issn = {1466-5026}, mesh = {Bacteria/classification ; Chloroflexi/*classification/*genetics/growth & development/ultrastructure ; Microscopy, Electron ; Molecular Sequence Data ; *Phylogeny ; }, abstract = {Two thermophilic, Gram-negative, non-spore-forming, multicellular filamentous micro-organisms were isolated from thermophilic granular sludge in an upflow anaerobic sludge blanket reactor treating fried soybean-curd manufacturing waste water (strain UNI-1(T)) and from a hot spring sulfur-turf in Japan (strain STL-6-O1(T)). The filaments were longer than 100 microm and of 0.2-0.3 microm (strain UNI-1(T)) or 0.7-0.8 microm (strain STL-6-O1(T)) in width. Strain UNI-1(T) was a strictly anaerobic organism. The optimum temperature for growth was around 55 degrees C; growth occurred in the range 50-60 degrees C. The optimum pH for growth was around 7.0; growth occurred in the range pH 6.0-8.0. Strain STL-6-O1(T) was a facultatively aerobic bacterium. The optimum temperature for growth was around 55 degrees C; growth occurred in the range 37-65 degrees C. The optimum pH for growth was around 7.5-8.0; growth occurred in the range pH 7.0-9.0. The two organisms grew chemo-organotrophically on a number of carbohydrates and amino acids in the presence of yeast extract. The G+C content of the DNA of strains UNI-1(T) and STL-6-O1(T) was 54.5 and 59.0 mol%, respectively. Major cellular fatty acids for strain UNI-1(T) were C(16 : 0), C(15 : 0), C(14 : 0) and C(18 : 0), whereas those for strain STL-6-O1(T) were C(18 : 0), C(16 : 0), C(17 : 0) and iso-C(17 : 0). MK-10 was the major quinone from aerobically grown STL-6-O1(T) cells. Phylogenetic analyses based on 16S rDNA sequences revealed that both strains belong to an uncultured, previously recognized clone lineage of the phylum Chloroflexi (formerly known as green non-sulfur bacteria). These phenotypic and genetic properties suggested that each strain should be classified into a new independent genus; hence, the names Anaerolinea thermophila and Caldilinea aerophila are proposed for strains UNI-1(T) (=JCM 11387(T)=DSM 14523(T)) and STL-6-O1(T)(=JCM 11388(T)=DSM 14525(T)), respectively. These strains represent the type and sole species of the genera Anaerolinea and Caldilinea, respectively.}, } @article {pmid14657097, year = {2003}, author = {Taylor, FJ}, title = {The collapse of the two-kingdom system, the rise of protistology and the founding of the International Society for Evolutionary Protistology (ISEP).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {53}, number = {Pt 6}, pages = {1707-1714}, doi = {10.1099/ijs.0.02587-0}, pmid = {14657097}, issn = {1466-5026}, mesh = {Animals ; Biological Evolution ; Fungi/classification/ultrastructure ; Microbiology ; *Phylogeny ; }, abstract = {This paper provides a brief summary of the rise and acceptance of protistology as a modern, realistic approach to the evolutionary relationships and classification of unicellular eukaryotic organisms as well as the origins of the multicellular groups. The apparent reasons for the renaissance of this 19th-century concept in the 1970s are reviewed, with electron microscopy considered to be the key factor, strongly reinforced by molecular phylogenetic studies in the 1980s and 1990s. The foundation of the International Society for Evolutionary Protistology in 1975 accompanied this major alteration in the view of biological diversity. The current status of protistology relative to protozoology and phycology is discussed.}, } @article {pmid14644200, year = {2003}, author = {Thiery, JP}, title = {Epithelial-mesenchymal transitions in development and pathologies.}, journal = {Current opinion in cell biology}, volume = {15}, number = {6}, pages = {740-746}, doi = {10.1016/j.ceb.2003.10.006}, pmid = {14644200}, issn = {0955-0674}, mesh = {Animals ; Carcinoma/pathology ; Cell Line ; Epithelial Cells/pathology ; Epithelium/*pathology ; GTP Phosphohydrolases/metabolism ; Humans ; Mesoderm/*pathology ; Models, Biological ; Morphogenesis ; Phenotype ; Protein-Tyrosine Kinases/*metabolism ; Signal Transduction ; Transcription, Genetic ; Transforming Growth Factor beta/metabolism ; }, abstract = {The epithelial-mesenchymal transition (EMT) is a fundamental process governing morphogenesis in multicellular organisms. This process is also reactivated in a variety of diseases including fibrosis and in the progression of carcinoma. The molecular mechanisms of EMT were primarily studied in epithelial cell lines, leading to the discovery of transduction pathways involved in the loss of epithelial cell polarity and the acquisition of a variety of mesenchymal phenotypic traits. Similar mechanisms have also been uncovered in vivo in different species, showing that EMT is controlled by remarkably well-conserved mechanisms. Current studies further emphasise the critical importance of EMT and provide a better molecular and functional definition of mesenchymal cells and how they emerged >500 million years ago as a key event in evolution.}, } @article {pmid14638321, year = {2003}, author = {Brooke, NM and Holland, PW}, title = {The evolution of multicellularity and early animal genomes.}, journal = {Current opinion in genetics & development}, volume = {13}, number = {6}, pages = {599-603}, doi = {10.1016/j.gde.2003.09.002}, pmid = {14638321}, issn = {0959-437X}, mesh = {Animals ; Cnidaria/*genetics ; DNA, Mitochondrial/*genetics ; *Evolution, Molecular ; Gene Expression Regulation ; Genes, Homeobox ; Mesoderm ; Phosphotransferases/genetics ; *Phylogeny ; Signal Transduction ; }, abstract = {Several independent molecular datasets, including complete mtDNA sequence, indicate that Choanozoa are most closely related to multicellular animals. There is still confusion concerning basal animal phylogeny, although recent data indicate that Placozoa are not degenerate cnidarians and hence (along with sponges) occupy a pivotal position. The transition in evolution from diploblast to bilaterian animals is becoming better understood, with gene expression data arguing that cnidarians have forerunners of the anteroposterior and dorsoventral body axes, and even a putative homologue of mesoderm. The homeobox and kinase gene families have been further analysed in basal animals, although more data are required to enable detailed comparison with Bilateria.}, } @article {pmid14638318, year = {2003}, author = {Sankoff, D}, title = {Rearrangements and chromosomal evolution.}, journal = {Current opinion in genetics & development}, volume = {13}, number = {6}, pages = {583-587}, doi = {10.1016/j.gde.2003.10.006}, pmid = {14638318}, issn = {0959-437X}, mesh = {Animals ; Chromosome Breakage ; Eukaryotic Cells ; *Evolution, Molecular ; *Gene Rearrangement ; *Genome ; Genomics ; *Models, Theoretical ; Prokaryotic Cells ; }, abstract = {Comparisons of the genome sequences of related species suggests varying patterns of chromosomal rearrangements in different evolutionary lineages. In this review, I focus on the quantitative characterization of rearrangement processes and discuss specific inventories that have been compiled to date. Of particular interest are the statistical distribution of the lengths of inverted or locally transposed chromosome fragments (notably very short ones), inhomogeneities in susceptibility to evolutionary breakpoints in chromosomal regions, the relative importance of genome doubling in the history of multicellular eukaryotes, and of lateral transfer versus gene gain and loss in prokaryotes. These developments provide challenges to computational biologists to refine, revise and scale up mathematical models and algorithms for analyzing genome rearrangements.}, } @article {pmid14635845, year = {2003}, author = {Cuevas, JM and Moya, A and Elena, SF}, title = {Evolution of RNA virus in spatially structured heterogeneous environments.}, journal = {Journal of evolutionary biology}, volume = {16}, number = {3}, pages = {456-466}, doi = {10.1046/j.1420-9101.2003.00547.x}, pmid = {14635845}, issn = {1010-061X}, mesh = {*Adaptation, Biological ; *Biological Evolution ; *Environment ; In Vitro Techniques ; *Models, Theoretical ; Population Dynamics ; RNA Viruses/*genetics/physiology ; }, abstract = {A hallmark of the infectious cycle for many RNA viruses parasitizing multicellular hosts is the need to invade and successfully replicate in tissues that comprise a variety of cell types. Thus, multicellular hosts represent a heterogeneous environment to evolving viral populations. To understand viral adaptation to multicellular hosts, we took a double approach. First, we developed a mathematical model that served to make predictions concerning the dynamics of viral populations evolving in heterogeneous environments. Second, the predictions were tested by evolving vesicular stomatitis virus in vitro on a spatially structured environment formed by three different cell types. In the absence of gene flow, adaptation was tissue-specific, but fitness in all tissues decreased with migration rate. The performance in a given tissue was negatively correlated with its distance to the tissue hosting the population. This correlation decreased with migration rate.}, } @article {pmid14635798, year = {2003}, author = {Murtagh, J and Martin, F and Gronostajski, RM}, title = {The Nuclear Factor I (NFI) gene family in mammary gland development and function.}, journal = {Journal of mammary gland biology and neoplasia}, volume = {8}, number = {2}, pages = {241-254}, pmid = {14635798}, issn = {1083-3021}, support = {DK48796/DK/NIDDK NIH HHS/United States ; DK58401/DK/NIDDK NIH HHS/United States ; HD34908/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; CCAAT-Enhancer-Binding Proteins/*genetics/metabolism ; Chickens ; *DNA-Binding Proteins ; Female ; Gene Expression Regulation, Developmental ; Humans ; Lactation ; Mammary Glands, Animal/*embryology/physiology ; Mammary Glands, Human/*embryology/physiology ; Mice ; Models, Genetic ; NFI Transcription Factors ; Nuclear Proteins ; Rats ; Transcription Factors/metabolism ; Transcription, Genetic ; Y-Box-Binding Protein 1 ; }, abstract = {Mammary gland development and function require the coordinated spatial and temporal expression of a large fraction of the mammalian genome. A number of site-specific transcription factors are essential to achieve the appropriate growth, branching, expansion, and involution of the mammary gland throughout early postnatal development and the lactation cycle. One family of transcription factors proposed to play a major role in the mammary gland is encoded by the Nuclear Factor I (NFI) genes. The NFI gene family is found only in multicellular animals, with single genes being present in flies and worms and four genes in vertebrates. While the NFI family expanded and diversified prior to the evolution of the mammary gland, it is clear that several mammary-gland specific genes are regulated by NFI proteins. Here we address the structure and evolution of the NFI gene family and examine the role of the NFI transcription factors in the expression of mammary-gland specific proteins, including whey acidic protein and carboxyl ester lipase. We discuss current data showing that unique NFI proteins are expressed during lactation and involution and suggest that the NFI gene family likely has multiple important functions throughout mammary gland development.}, } @article {pmid14631042, year = {2003}, author = {Lynch, M and Conery, JS}, title = {The origins of genome complexity.}, journal = {Science (New York, N.Y.)}, volume = {302}, number = {5649}, pages = {1401-1404}, doi = {10.1126/science.1089370}, pmid = {14631042}, issn = {1095-9203}, mesh = {Alleles ; Animals ; Bacteria/genetics ; Body Constitution ; Eukaryota/genetics ; *Evolution, Molecular ; Fungi/genetics ; Gene Duplication ; Gene Silencing ; Genetic Drift ; Genetic Variation ; *Genome ; Humans ; Interspersed Repetitive Sequences ; Introns ; Invertebrates/genetics ; Mutation ; *Phylogeny ; Plants/genetics ; Population Density ; Recombination, Genetic ; Selection, Genetic ; Spliceosomes ; Vertebrates/genetics ; }, abstract = {Complete genomic sequences from diverse phylogenetic lineages reveal notable increases in genome complexity from prokaryotes to multicellular eukaryotes. The changes include gradual increases in gene number, resulting from the retention of duplicate genes, and more abrupt increases in the abundance of spliceosomal introns and mobile genetic elements. We argue that many of these modifications emerged passively in response to the long-term population-size reductions that accompanied increases in organism size. According to this model, much of the restructuring of eukaryotic genomes was initiated by nonadaptive processes, and this in turn provided novel substrates for the secondary evolution of phenotypic complexity by natural selection. The enormous long-term effective population sizes of prokaryotes may impose a substantial barrier to the evolution of complex genomes and morphologies.}, } @article {pmid14623229, year = {2003}, author = {Rudel, D and Sommer, RJ}, title = {The evolution of developmental mechanisms.}, journal = {Developmental biology}, volume = {264}, number = {1}, pages = {15-37}, doi = {10.1016/s0012-1606(03)00353-1}, pmid = {14623229}, issn = {0012-1606}, mesh = {Animals ; *Biological Evolution ; *Body Patterning/genetics/physiology ; Cell Division/physiology ; Cell Lineage ; *Developmental Biology ; Embryo, Mammalian/anatomy & histology/*physiology ; *Embryo, Nonmammalian ; Embryonic Induction ; Eye/anatomy & histology/embryology ; Gonads/anatomy & histology/physiology ; *Morphogenesis ; Quantitative Trait Loci ; Skeleton ; }, abstract = {Over the past two to three decades, developmental biology has demonstrated that all multicellular organisms in the animal kingdom share many of the same molecular building blocks and many of the same regulatory genetic pathways. Yet we still do not understand how the various organisms use these molecules and pathways to assume all the forms we know today. Evolutionary developmental biology tackles this problem by comparing the development of one organism to another and comparing the genes involved and gene functions to understand what makes one organism different from another. In this review, we revisit a set of seven concepts defined by Lewis Wolpert (fate maps, asymmetric division, induction, competence, positional information, determination, and lateral inhibition) that describe the characters of many developmental systems and supplement them with three additional concepts (developmental genomics, genetic redundancy, and genetic networks). We will discuss examples of comparative developmental studies where these concepts have guided observations on the advent of a developmental novelty. Finally, we identify a set of evolutionary frameworks, such as developmental constraints, cooption, duplication, parallel and convergent evolution, and homoplasy, to adequately describe the evolutionary properties of developmental systems.}, } @article {pmid14607565, year = {2003}, author = {Nabeshima, H and Murakami, T and Yoshinaga, K and Sato, K and Terada, Y and Okamura, K}, title = {Analysis of the clonality of ectopic glands in peritoneal endometriosis using laser microdissection.}, journal = {Fertility and sterility}, volume = {80}, number = {5}, pages = {1144-1150}, doi = {10.1016/s0015-0282(03)01181-6}, pmid = {14607565}, issn = {0015-0282}, mesh = {Clone Cells/*pathology ; DNA Methylation ; Endometriosis/*pathology ; Female ; Heterozygote ; Homozygote ; Humans ; Hysteroscopy ; Laser Therapy ; Microdissection ; Peritoneal Diseases/*pathology ; Phosphoglycerate Kinase/genetics ; Polymorphism, Genetic ; Prospective Studies ; }, abstract = {OBJECTIVE: To investigate the clonality of ectopic gland cells in peritoneal endometriosis.

DESIGN: Prospective study. University hospital.

PATIENT(S): Seventeen women with surgically diagnosed endometriosis.

INTERVENTION(S): Samples of peritoneal endometriotic lesions were obtained from patients during laparoscopic surgery.

MAIN OUTCOME MEASURE(S): Clonality analysis used the laser microdissection technique, a phosphoglycerate kinase (PGK) gene polymorphism assay, and an androgen receptor (AR) gene polymorphism assay after digestion of the DNA with methylation-sensitive endonuclease.

RESULT(S): Each ectopic gland of the peritoneal endometriotic lesion showed a monoclonal pattern in both the PGK gene and AR gene assays, but the methylation pattern of the PGK gene and/or AR gene was divergent among adjacent glands in the lesion. These data indicate that the peritoneal endometriotic lesions are multicellular in origin, although individual glands of the lesion are derived from single precursor cells.

CONCLUSION(S): The colored peritoneal endometriotic lesion in the present study was multicellular in origin. Peritoneal endometriotic lesions may thus be initiated by transplantation of a cluster of eutopic endometrial tissues into the pelvis.}, } @article {pmid14607202, year = {2003}, author = {Stumpf, C and Lehner, C and Eskafi, S and Raaz, D and Yilmaz, A and Ropers, S and Schmeisser, A and Ludwig, J and Daniel, WG and Garlichs, CD}, title = {Enhanced levels of CD154 (CD40 ligand) on platelets in patients with chronic heart failure.}, journal = {European journal of heart failure}, volume = {5}, number = {5}, pages = {629-637}, doi = {10.1016/s1388-9842(03)00110-7}, pmid = {14607202}, issn = {1388-9842}, mesh = {Aged ; Aspirin/therapeutic use ; Blood Platelets/immunology/*metabolism ; CD40 Ligand/*analysis/metabolism ; Case-Control Studies ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Heart Failure/*blood/drug therapy/immunology ; Humans ; Male ; Middle Aged ; P-Selectin/blood ; Pilot Projects ; Platelet Aggregation Inhibitors/therapeutic use ; }, abstract = {BACKGROUND: Inflammation plays a significant contributory role in the pathogenesis of chronic heart failure (CHF). Previous data have shown enhanced plasma levels of proinflammatory cytokines, i.e. TNF-alpha and IL-6, as well as a persistent immune activation in patients with CHF. Furthermore, the immune modulator CD154 has been receiving increased attention, since it plays a key role in the pathophysiology of multicellular vascular events such as thrombosis, inflammation and atherosclerosis. Since CD154 initiates and maintains the release of proinflammatory cytokines from endothelial cells, its potential role for the development and progression of CHF is of interest.

METHODS: Fifty patients with CHF (aged 66.9+/-12.6 years, mean ejection fraction 22.1+/-9.2%, NYHA II-IV, 39 of ischemic origin, 11 with idiopathic dilated cardiomyopathy) and 15 healthy controls (aged 62.5+/-9.8 years) were examined. Thirty-two patients were taking aspirin (100 mg/day). Blood was drawn from a peripheral vein and immediately fixed with 1% paraformaldehyde, incubated with anti-CD154, anti-P-selectin, and anti-CD61 and thereafter analyzed by flow cytometry.

RESULTS: Patients with CHF showed significantly enhanced expression of platelet-bound CD154 and P-selectin as compared to controls (CD154: median 35.6 25th percentile: 26.3; 75th percentile: 44.6 vs. 12.8; 25th: 6.8; 75th: 15.6 mean fluorescence intensity [MFI], P<0.001; P-selectin: median 3.2 25th percentile: 1.9; 75th percentile: 5.9 vs. 1.4; 25th: 1.2; 75th: 1.9, MFI, P<0.001). CD154 expression on platelets positively correlated with increasing NYHA-class. In contrast, no significant differences in serum levels of soluble CD154 or CD40 expression on monocytes were detected in the study groups. Antiplatelet-therapy with aspirin did not influence CD154 or P-selectin expression on platelets.

CONCLUSION: Our pilot study demonstrates significantly enhanced levels of CD154 on platelets in patients with CHF. This suggests that the CD40-CD154 axis may contribute to the proinflammatory milieu, which exists in CHF and thus may play a pathogenic role in the development and progression of CHF.}, } @article {pmid14604590, year = {2003}, author = {Michor, F and Frank, SA and May, RM and Iwasa, Y and Nowak, MA}, title = {Somatic selection for and against cancer.}, journal = {Journal of theoretical biology}, volume = {225}, number = {3}, pages = {377-382}, doi = {10.1016/s0022-5193(03)00267-4}, pmid = {14604590}, issn = {0022-5193}, mesh = {Animals ; Apoptosis ; Cell Division/genetics ; *Genes, Tumor Suppressor ; Genetic Drift ; Models, Biological ; Mutation ; Neoplasms/*genetics/pathology ; *Oncogenes ; }, abstract = {In multicellular organisms, cells cooperate within a well-defined developmental program. Cancer is a breakdown of such cooperation: cells mutate to phenotypes of uncoordinated proliferation. We study basic principles of the architecture of solid tissues that influence the rate of cancer initiation. In particular, we explore how somatic selection acts to prevent or to promote cancer. Cells with mutations in oncogenes or tumor suppressor genes often have increased proliferation rates. Somatic selection increases their abundance and thus enhances the risk of cancer. Many potentially harmful mutations, however, increase the probability of triggering apoptosis and, hence, initially lead to cells with reduced net proliferation rates. Such cells are eliminated by somatic selection, which therefore also works to reduce the risk of cancer. We show that a tissue organization into small compartments avoids the rapid spread of mutations in oncogenes and tumor suppressor genes, but promotes genetic instability. In small compartments, genetic instability, which confers a selective disadvantage for the cell, can spread by random drift. If both deleterious and advantageous mutations participate in tumor initiation, then we find an intermediate optimum for the compartment size.}, } @article {pmid14597727, year = {2004}, author = {Kobayashi, KS and Flavell, RA}, title = {Shielding the double-edged sword: negative regulation of the innate immune system.}, journal = {Journal of leukocyte biology}, volume = {75}, number = {3}, pages = {428-433}, doi = {10.1189/jlb.0703321}, pmid = {14597727}, issn = {0741-5400}, mesh = {Animals ; *Down-Regulation ; Endotoxins/immunology/pharmacology ; Humans ; Immune System/*metabolism/pathology ; Immune Tolerance ; Membrane Glycoproteins/*immunology/physiology ; Receptors, Cell Surface/*immunology/physiology ; Signal Transduction ; Toll-Like Receptors ; }, abstract = {The innate immune system is evolutionarily conserved among all multicellular organisms and is the first line of defense against microorganisms. It enables the host not only to combat pathogenic organisms but also to cohabit with nonpathogenic microorganisms by balancing the host-microorganism interaction. The innate immune response is activated rapidly (within hours) compared with adaptive immunity. Activation of the innate immune system allows the activation of the adaptive immune response by production of proinflammatory cytokines and by providing stimulatory signals via major histocompatibility complex molecules and costimulatory molecules such as CD40, CD80, or CD86; together, these lead to the full activation of both immune systems to fight against pathogenic microorganisms. Activation of the innate immune system, however, can be a double-edged sword for the host. Proinflammatory cytokines mediate a positive feedback loop on the innate immune system, and overproduction of cytokines, if unchecked, is hazardous to the host and may cause severe outcomes such as hyperthermia, organ failure, and even death in extreme cases. Moreover, if the overproduction of proinflammatory cytokines persists, it may cause chronic inflammatory diseases. During evolution, the innate immune system has acquired complicated regulatory systems to control itself so that this "sword" will not kill the host. Various mechanisms including inhibition of Toll-like receptor signaling by interleukin-1 receptor-associated kinase-M have evolved for this purpose and are important not only to fight against pathogenic microorganisms efficiently but also are critical for the peaceful coexistence with commensal bacterial flora.}, } @article {pmid14585077, year = {2003}, author = {deCathelineau, AM and Henson, PM}, title = {The final step in programmed cell death: phagocytes carry apoptotic cells to the grave.}, journal = {Essays in biochemistry}, volume = {39}, number = {}, pages = {105-117}, doi = {10.1042/bse0390105}, pmid = {14585077}, issn = {0071-1365}, mesh = {Animals ; *Apoptosis ; Caenorhabditis elegans/genetics ; Drosophila melanogaster/genetics ; Evolution, Molecular ; Inflammation/metabolism ; Mice/genetics ; Models, Biological ; Phagocytes/*physiology ; *Phagocytosis ; Receptors, Cell Surface/metabolism ; Signal Transduction ; }, abstract = {As cells undergo apoptosis, they are recognized and removed from the body by phagocytes. This oft-overlooked yet critical final step in the cell-death programme protects tissues from exposure to the toxic contents of dying cells and also serves to prevent further tissue damage by stimulating production of anti-inflammatory cytokines and chemokines. The clearance of apoptotic-cell corpses occurs throughout the lifespan of multicellular organisms and is important for normal development during embryogenesis, the maintenance of normal tissue integrity and function, and the resolution of inflammation. Many of the signal-transduction molecules implicated in the phagocytosis of apoptotic cells appear to have a high degree of evolutionary conservation, and therefore the engulfment of apoptotic cells is likely to represent one of the most primitive forms of phagocytosis. With the realization that the signals that govern apoptotic-cell removal also serve to attenuate inflammation and the immune response, as well as initiate signals for tissue repair and remodelling in response to cell death, the study of apoptotic cell clearance is a field experiencing a dynamic increase in interest and momentum.}, } @article {pmid14585071, year = {2003}, author = {McCarthy, JV}, title = {Apoptosis and development.}, journal = {Essays in biochemistry}, volume = {39}, number = {}, pages = {11-24}, doi = {10.1042/bse0390011}, pmid = {14585071}, issn = {0071-1365}, mesh = {Animals ; *Apoptosis ; Caenorhabditis elegans/growth & development/*physiology ; Cell Lineage ; Conserved Sequence ; Drosophila melanogaster/growth & development/*physiology ; Ecdysone/metabolism ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Mice ; Models, Animal ; }, abstract = {Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.}, } @article {pmid21312115, year = {2001}, author = {Chiarugi, V and Cinelli, M and Magnelli, L and Dello Sbarba, P}, title = {Apoptosis : molecular regulation of cell death and hematologic malignancies.}, journal = {Methods in molecular medicine}, volume = {55}, number = {}, pages = {323-338}, doi = {10.1385/1-59259-074-8:323}, pmid = {21312115}, issn = {1543-1894}, abstract = {Apoptosis, or programmed cell death, represents in cell biology a functional program as important as cell growth or differentiation. Programmed cell death is of basic importance for the development of multicellular organisms and its basic mechanisms are conserved during the evolution of metazoa. Mammalian cells exhibit several different apoptotic pathways that converge to a common endpoint. Each pathway is triggered by a different stimulus: growth factor default, irradiation, induction of the p53 oncosuppressor protein, glucocorticoid hormones (in lymphocytes), ligand binding to Fas/APO (CD95), or tumor necrosis factor receptor (TNF-R), perforin secreted by cytotoxic T cells (reviewed by Hale et al. [1]). As opposed to necrosis, apoptosis is a "clean" process: as the cell shrinks, the cell membrane turns into the "apoptotic shell," the nucleus is condensed and reduced in volume, and eventually the cell disappears from the tissue, due to phagocytosis by neighboring cells or professional phagocytes, such as macrophages.}, } @article {pmid21238227, year = {1998}, author = {Fagerström, T and Briscoe, DA and Sunnucks, P}, title = {Evolution of mitotic cell-lineages in multicellular organisms.}, journal = {Trends in ecology & evolution}, volume = {13}, number = {3}, pages = {117-120}, doi = {10.1016/S0169-5347(97)01314-1}, pmid = {21238227}, issn = {0169-5347}, abstract = {Adaptive evolution in multicellular organisms is generally assumed to occur through natural selection acting differentially among the phenotypes programmed by sexually-generated zygotic genotypes. Under this view, only genetic changes in the gamete-zygote-germline-gamete cycle are considered relevant to the evolutionary process. Yet asexuality - production of progeny through proliferation of mitotic cell-lineages - is found in over one half of all eukaryotic phyla, and is likely to contribute to adaptive changes, as suggested by recent evidence from both animals and plants. Adaptive changes in mitotic lineages can be reconciled with contemporary evolutionary thought by fully abandoning the weismannian concept of individuality.}, } @article {pmid18811312, year = {1997}, author = {Michod, RE}, title = {Evolution of the individual.}, journal = {The American naturalist}, volume = {150 Suppl 1}, number = {}, pages = {S5-S21}, doi = {10.1086/286047}, pmid = {18811312}, issn = {0003-0147}, abstract = {This article studies the transition in evolution from single cells to multicellular organisms as a case study in the origin of individuality. The issues considered are applicable to all major transitions in the units of selection that involve the emergence of cooperation and the regulation of conflict. Explicit genetic models of mutation and selection both within and between organisms are studied. Cooperation among cells increases when the fitness covariance at the level of the organism overcomes within-organism change toward defection. Selection and mutation during development generate significant levels of within-organism variation and lead to variation in organism fitness at equilibrium. This variation selects for gem-line modifiers and other mediators of within-organism conflict, increasing the heritability of fitness at the organism level. The evolution of these modifiers is the first new function at the emerging organism level and a necessary component of the evolution of individuality.}, } @article {pmid15157515, year = {1996}, author = {Roemer, T and Vallier, LG and Snyder, M}, title = {Selection of polarized growth sites in yeast.}, journal = {Trends in cell biology}, volume = {6}, number = {11}, pages = {434-441}, doi = {10.1016/s0962-8924(96)10039-8}, pmid = {15157515}, issn = {0962-8924}, abstract = {The budding yeast Saccharomyces cerevisiae responds to intracellular and extracellular cues to direct cell growth. Genetic analysis has revealed many components that participate in this process and has provided insight into the mechanisms by which these proteins function. Several of these components, such as the septins, pheromone receptors and GTPase proteins, have homologues in multicellular eukaryotes, suggesting that many aspects of polarized cell growth may be conserved throughout evolution. This review discusses our current understanding of the molecular mechanisms of growth-site selection during the different stages of the yeast life cycle.}, } @article {pmid17180034, year = {1995}, author = {Ameisen, JC and Idziorek, T and Billaut-Mulot, O and Loyens, M and Tissier, JP and Potentier, A and Ouaissi, A}, title = {Apoptosis in a unicellular eukaryote (Trypanosoma cruzi): implications for the evolutionary origin and role of programmed cell death in the control of cell proliferation, differentiation and survival.}, journal = {Cell death and differentiation}, volume = {2}, number = {4}, pages = {285-300}, pmid = {17180034}, issn = {1350-9047}, abstract = {The origin of programmed cell death (PCD) has been linked to the emergence of multicellular organisms. Trypanosoma cruzi, a member of one of the earliest diverging eukaryotes, is a protozoan unicellular parasite that undergoes three major differentiation changes and requires two different hosts. We report that the in vitro differentiation of the proliferating epimastigote stage into the G0/G1 arrested trypomastigote stage is associated with massive epimastigote death that shows the cytoplasmic and nuclear morphological features and DNA fragmentation pattern of apoptosis, the most frequent phenotype of PCD in multicellular organisms. Apoptosis could be accelerated or prevented by modifying culture conditions or cell density, indicating that extracellular signals influenced the epimastigote decision between life and death. Epimastigotes responded to complement-mediated immunological agression by undergoing apoptosis, while undergoing necrosis in response to nonphysiological saponin-mediated damage. PCD may participate into the optimal adaptation of T. cruzi to its different hosts, and the avoidance of a local competition between a G0/G1 arrested stage and its proliferating progenitor. The existence of a regulated cell death programme inducing an apoptotic phenotype in a unicellular eukaryote provides a paradigm for a widespread role for PCD in the control of cell survival, which extends beyond the evolutionary constraints that may be specific to multicellular organisms and raises the question of the origin and nature of the genes involved. Another implication is that PCD induction could represent a target for therapeutic strategies against unicellular pathogens.}, } @article {pmid21236876, year = {1994}, author = {Schlegel, M}, title = {Molecular phylogeny of eukaryotes.}, journal = {Trends in ecology & evolution}, volume = {9}, number = {9}, pages = {330-335}, doi = {10.1016/0169-5347(94)90153-8}, pmid = {21236876}, issn = {0169-5347}, abstract = {Comparisons of ribosomal RNAs and various protein coding genes have contributed to a new view of eukaryote phylogeny. Analyses of paralogous protein coding genes suggest that archaebacteria and eukaryotes are sistergroups. Sequence diversity of small subunit rRNAs in protists by far exceeds that of any multicellular or prokaryote taxon. Remarkably, a group of taxa that lack mitochondria first branches off in the small subunit rRNA tree. The later radiations are formed by a series of clades that were once thought to be more ancestral. Furthermore, tracing of the evolutionary origin of secondary endobiontic events is now possible with sequence comparisons.}, } @article {pmid14731901, year = {1993}, author = {Riezman, H}, title = {Three clathrin-dependent budding steps and cell polarity.}, journal = {Trends in cell biology}, volume = {3}, number = {10}, pages = {330-332}, doi = {10.1016/0962-8924(93)90097-k}, pmid = {14731901}, issn = {0962-8924}, abstract = {Clathrin plays an important role in the vesicular transport of proteins in all eukaryotes, but the precise steps in which it is involved may not be identical in all of them. Here, I put forward the hypothesis that three distinct clathrin-dependent budding events are common to all eukaryotes and have the following distinctive features: the first requires actin, the second is used for targeting soluble hydrolases from the Golgi to the hydrolytic compartment, and the third uses a tyrosine localization signal to concentrate membrane proteins. I suggest that the latter budding step is found on endosomes in yeast and is used for retrieval of membrane proteins back to the Golgi. Several testable predictions arise from this hypothesis as well as a possible evolutionary scenario concerning the origin of basolateral and apical plasma membranes in multicellular organisms.}, } @article {pmid21235940, year = {1992}, author = {Valero, M and Richerd, S and Perrot, V and Destombe, C}, title = {Evolution of alternation of haploid and diploid phases in life cycles.}, journal = {Trends in ecology & evolution}, volume = {7}, number = {1}, pages = {25-29}, doi = {10.1016/0169-5347(92)90195-H}, pmid = {21235940}, issn = {0169-5347}, abstract = {Eukaryotic sex leads to an alternation of haploid and diploid nuclear phases. Because all multicellular animals are diploid, diploidy is often considered a 'biological success' and many arguments have been advanced to explain the evolution of a prolonged diploid phase. Nevertheless, among eukaryotes three basic situations are encountered, where the vegetative individuals are diploid or haploid or both. These three basic life cycles are widely distributed among kingdoms and in some taxa the occurrence of different life cycles within the same species has been reported. This article briefly summarizes the different hypotheses on the evolution of reproductive life cycles and underlines how possibilities of variation for this trait may open new perspectives for research.}, } @article {pmid16594021, year = {1989}, author = {Gray, MW and Cedergren, R and Abel, Y and Sankoff, D}, title = {On the evolutionary origin of the plant mitochondrion and its genome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {86}, number = {7}, pages = {2267-2271}, pmid = {16594021}, issn = {0027-8424}, abstract = {Higher plants occupy very different positions in the mitochondrial and nuclear lineages of global phylogenetic trees based on conserved regions of small subunit (SSU) and large subunit (LSU) rRNA sequences. In the nuclear subtree, plants branch off late, at a position reflecting a massive radiation of the major multicellular (and some unicellular) groups; in the mitochondrial subtree, in contrast, plants branch off early, near the point of connection between the mitochondrial and eubacterial lineages. Moreover, in the nuclear lineage, plants branch together with the unicellular green alga Chlamydomonas reinhardtii, whereas in the mitochondrial lineage (in both SSU and LSU trees), metaphytes and chlorophyte branch separately. Statistical evaluation indicates that the anomalous branching position of higher plants in the mitochondrial lineage is not a treeing artifact attributable to the relatively rapid rate of sequence divergence of non-plant mitochondrial rRNA sequences. In considering alternative biological explanations for these results, we are led to propose that the rRNA genes in plant mitochondria may be of more recent evolutionary origin than the rRNA genes in other mitochondria. This proposal has implications for monophyletic vs. polyphyletic scenarios of mitochondrial origin and is consistent with other evidence indicating that plant mtDNA is an evolutionary mosaic.}, } @article {pmid21227834, year = {1987}, author = {Rayner, AD and Franks, NR}, title = {Evolutionary and ecological parallels between ants and fungi.}, journal = {Trends in ecology & evolution}, volume = {2}, number = {5}, pages = {127-133}, doi = {10.1016/0169-5347(87)90053-X}, pmid = {21227834}, issn = {0169-5347}, abstract = {Despite their different fundamental organization, ant colonies and mycelia of fungi exhibit striking similarities in their social organization. Both are collectives of genetically related or identical semi-autonomous units, consisting respectively of discrete multicellular individuals and hyphae. There is a variety of parallels in their foraging and resource capture strategies, developmental versatility and division of labour, and in the interactions between non-self recognition phenomena resulting in sexual or parasitic invasion of foreign genes into the collective, or in rejection of non-self. These parallels lend a new perspective to the nutritional relationships and modes of communication between developmentally different phases in collective systems of interacting individual units. They also have important evolutionary implications for the origin and regulation of mechanisms of gene flow between different colonies or collectives, including a link between mechanisms underlying sex, parasitism and sympatric speciation.}, } @article {pmid16593540, year = {1985}, author = {Hori, H and Lim, BL and Osawa, S}, title = {Evolution of green plants as deduced from 5S rRNA sequences.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {82}, number = {3}, pages = {820-823}, pmid = {16593540}, issn = {0027-8424}, abstract = {We have constructed a phylogenic tree for green plants by comparing 5S rRNA sequences. The tree suggests that the emergence of most of the uni- and multicellular green algae such as Chlamydomonas, Spirogyra, Ulva, and Chlorella occurred in the early stage of green plant evolution. The branching point of Nitella is a little earlier than that of land plants and much later than that of the above green algae, supporting the view that Nitella-like green algae may be the direct precursor to land plants. The Bryophyta and the Pteridophyta separated from each other after emergence of the Spermatophyta. The result is consistent with the view that the Bryophyta evolved from ferns by degeneration. In the Pteridophyta, Psilotum (whisk fern) separated first, and a little later Lycopodium (club moss) separated from the ancestor common to Equisetum (horsetail) and Dryopteris (fern). This order is in accordance with the classical view. During the Spermatophyta evolution, the gymnosperms (Cycas, Ginkgo, and Metasequoia have been studied here) and the angiosperms (flowering plants) separated, and this was followed by the separation of Metasequoia and Cycas (cycad)/Ginkgo (maidenhair tree) on one branch and various flowering plants on the other.}, } @article {pmid17736164, year = {1983}, author = {Norris, R and Smith, RH and Vaughn, KC}, title = {Plant Chimeras Used to Establish de novo Origin of Shoots.}, journal = {Science (New York, N.Y.)}, volume = {220}, number = {4592}, pages = {75-76}, doi = {10.1126/science.220.4592.75}, pmid = {17736164}, issn = {0036-8075}, abstract = {When African violet leaf explants are cultured in vitro, buds and shoots develop directly from the upper leaf surfaces. Three developmentally different African violet chimeras were cultured, and in each case adventitious shoots that developed into plants had the parent chimera pattern. A multicellular origin of the adventitious buds accounts for these results.}, } @article {pmid17784357, year = {1982}, author = {Lipscomb, DL and Corliss, JO}, title = {Stephanopogon, a phylogenetically important "ciliate," shown by ultrastructural studies to be a flagellate.}, journal = {Science (New York, N.Y.)}, volume = {215}, number = {4530}, pages = {303-304}, doi = {10.1126/science.215.4530.303}, pmid = {17784357}, issn = {0036-8075}, abstract = {A benthic marine protist (Stephanopogon) with a homokaryotic nucleus has long been considered to be a gymnostome ciliate. It has been important in hypotheses concerning the origin of ciliates, the evolution and origin of the dual nuclear apparatus of contemporary species of the Ciliophora, and the origin of the multicellular Eumetazoa. Ultrastructural observations reveal that the organism should be reclassified as a flagellate, despite its superficial resemblance to ciliates.}, } @article {pmid16592084, year = {1973}, author = {Stanley, SM}, title = {An ecological theory for the sudden origin of multicellular life in the late precambrian.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {70}, number = {5}, pages = {1486-1489}, pmid = {16592084}, issn = {0027-8424}, abstract = {According to modern ecological theory, high diversity at any trophic level of a community is possible only under the influence of cropping. Until herbivores evolved, single-celled algae of the Precambrain were resource-limited, and a small number of species saturated aquatic environments. In the near-absence of vacant niches, life diversified slowly. Because the changes required to produce the first algae-eating heterotrophs were therefore delayed, the entire system was self-limiting. When the "heterotroph barrier" was finally crossed in the late Precambrian, herbivorous and carnivorous protists arose almost simultaneously, for no major biological differences separate the two groups. These events automatically triggered the formation of a series of self-propagating feedback systems of diversification between adjacent trophic levels. Comparable systems arose among multi-cellular groups, which radiated rapidly from the newly diversifying protist taxa. The sudden proliferation of complex food webs formed by taxa invading previously vacant adaptive zones produced an explosive diversification of life over a period of a few tens of millions of years. The rapid appearance of skeletons in various groups, though of special geological importance, was no more dramatic than other aspects of the radiation. The overall rate of diversification was comparable to rates for less-extensive adaptive radiations of the Phanerozoic.}, } @article {pmid16562019, year = {1965}, author = {Atherton, JG and Chaparas, SD and Cremer, M and Gordon, I}, title = {Mechanism of Polykaryocytosis Associated with Noncytopathic Infection by Measles Virus.}, journal = {Journal of bacteriology}, volume = {90}, number = {1}, pages = {213-219}, pmid = {16562019}, issn = {0021-9193}, abstract = {Atherton, John G. (University of Southern California, Los Angeles), Sotiros G. Chaparas, Martha Cremer, and Irving Gordon. Mechanism of polykaryocytosis associated with noncytopathic infection by measles virus. J. Bacteriol. 90:213-219. 1965.-Infection with a measles virus variant resulted not only in formation of polykaryocytes (PK) but also in formation of multicellular immunofluorescent foci (IFF) in which no cytopathic effect could be detected. The ratio of IFF to PK changed from 27 to 4 during the first passage and remained 4 after a second passage. PK were plaques. Plaque assay was linear in the presence of IFF. To investigate the mechanism of PK formation, radioautography was done on cells pulse-labeled with tritiated thymidine before virus multiplication began. The results showed that PK were formed by fusion; there were no PK whose nuclei contained no label, and the proportion of labeled nuclei (32%) and distribution of grain counts was the same in PK as in uninvolved cells, ruling out nuclear replication without concomitant cytoplasmic membrane formation as the mechanism of formation of these PK. Early in PK development, neutral red uptake was markedly increased ("red" plaques). As PK matured, hyperchromicity disappeared ("white" plaques). This sequence provided an index of rate of evolution of PK. Rate of PK maturation was more rapid at 37 than at 32 C.}, } @article {pmid18213862, year = {1949}, author = {NETTLESHIP, A}, title = {[The tissue element in the origin of the new formations; morphological proof of the multicellular origin of new growths].}, journal = {Der Krebsarzt}, volume = {4}, number = {3}, pages = {115}, pmid = {18213862}, issn = {0368-6698}, mesh = {Humans ; Neoplasms/*etiology ; }, } @article {pmid20249643, year = {1947}, author = {NETTLESHIP, A}, title = {Tissue element in the origin of neoplasms; morphologic evidence that certain neoplasms have multicellular origin.}, journal = {Federation proceedings}, volume = {6}, number = {1}, pages = {398}, pmid = {20249643}, issn = {0014-9446}, mesh = {Humans ; *Neoplasms ; }, } @article {pmid14576276, year = {2003}, author = {Rodríguez-Trelles, F and Tarrío, R and Ayala, FJ}, title = {Convergent neofunctionalization by positive Darwinian selection after ancient recurrent duplications of the xanthine dehydrogenase gene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {100}, number = {23}, pages = {13413-13417}, pmid = {14576276}, issn = {0027-8424}, support = {GM42397/GM/NIGMS NIH HHS/United States ; }, mesh = {Aldehyde Oxidase/genetics ; Animals ; Binding Sites ; *Biological Evolution ; Cattle ; *Coenzymes ; Evolution, Molecular ; Flavin-Adenine Dinucleotide/chemistry ; Flavonoids/genetics ; *Gene Duplication ; Ligands ; Metalloproteins/genetics ; Molybdenum Cofactors ; Protein Binding ; Pteridines ; Xanthine Dehydrogenase/*genetics ; }, abstract = {Gene duplication is a primary source of molecular substrate for the emergence of evolutionary novelties. The chances for redundant gene sequences to evolve new functions are small compared with the probability that the copies become disabled by deleterious mutations. Functional divergence after gene duplication can result in two alternative evolutionary fates: one copy acquires a novel function (neofunctionalization), or each copy adopts part of the tasks of their parental gene (subfunctionalization). The relative prevalence of each outcome is unknown. Similarly unknown is the relative importance of positive selection versus random fixation of neutral mutations. Aldehyde oxidase (Ao) and xanthine dehydrogenase (Xdh) genes encode two complex members of the xanthine oxidase family of molybdo-flavoenzymes that carry different functions. Ao is known to have originated from a duplicate of an Xdh gene in eukaryotes, before the origin of multicellularity. We show that (i) Ao evolved independently twice from two different Xdh paralogs, the second time in the chordates, before the diversification of vertebrates; (ii) after each duplication, the Ao duplicate underwent a period of rapid evolution during which identical sites across the two molecules, involving the flavin adenine dinucleotide and substrate-binding pockets, were subjected to intense positive Darwinian selection; and (iii) the second Ao gene likely endured two periods of redundancy, initially as a duplicate of Xdh and later as a functional equivalent of the old Ao, which is currently absent from the vertebrate genome. Caution is appropriate in structural genomics when using sequence similarity for assigning protein function.}, } @article {pmid14566075, year = {2003}, author = {Grasselli, F and Basini, G and Tirelli, M and Cavalli, V and Bussolati, S and Tamanini, C}, title = {Angiogenic activity of porcine granulosa cells co-cultured with endothelial cells in a microcarrier-based three-dimensional fibrin gel.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {54}, number = {3}, pages = {361-370}, pmid = {14566075}, issn = {0867-5910}, mesh = {Animals ; Aorta/cytology/physiology ; Capillaries/cytology/growth & development ; Cell Movement ; Cell Size/physiology ; Cells, Cultured ; Coculture Techniques/*methods ; Endothelial Cells/*cytology/physiology ; Female ; *Fibrin ; *Gels ; Granulosa Cells/*cytology/physiology ; *Neovascularization, Physiologic ; Swine ; Time Factors ; }, abstract = {To verify the possible role played by pig granulosa cells in the ovarian angiogenic process, we have developed a reliable in vitro system which allows the evaluation of endothelial sprouting and capillary growth in three-dimensional matrices. Granulosa cells collected from porcine follicles of different size were co-cultured with porcine aortic endothelial cells (PAEC) in a microcarrier-based fibrin gel system; after 2 and 5 days of co-culture, we determined the number and length of all endothelial sprouts; moreover, these parameters were quantified only in capillary-like structures, which were defined as continuous multicellular sprouts at least 200 microm long. In granulosa cells- PAEC co-cultures we observed an increase of angiogenic activity as compared to controls (PAEC alone). Granulosa cells from follicles of different size regulate angiogenesis differently: cells from the small follicle group significantly enhanced endothelial sprouting, while those from the large follicle group favoured mainly capillary elongation. Our observations seem therefore to suggest that the development and growth of thecal vascular bed is controlled by paracrine factors of granulosa cell origin that may induce the formation of a primitive capillary plexus during the early phases of antral follicle growth, which will be remodelled in more advanced phases of follicular development.}, } @article {pmid14559806, year = {2003}, author = {Gatenby, RA and Vincent, TL}, title = {An evolutionary model of carcinogenesis.}, journal = {Cancer research}, volume = {63}, number = {19}, pages = {6212-6220}, pmid = {14559806}, issn = {0008-5472}, mesh = {Animals ; *Biological Evolution ; Carcinoma/*etiology/genetics/metabolism/pathology ; Cell Division/physiology ; Colorectal Neoplasms/etiology/genetics/metabolism/pathology ; Game Theory ; Humans ; *Models, Biological ; Mutation ; Neoplasm Invasiveness ; Neoplasms/*etiology/genetics/metabolism/pathology ; }, abstract = {A quantitative model of carcinogenesis based on methods from population biology and game theory demonstrates normal cells in vivo occupy a ridge-shaped maximum in a well-defined tissue fitness landscape, a novel configuration that allows cooperative coexistence of multiple cellular populations. This state, although necessary for development of functioning multicellular organisms, is subject to invasion by fitter, mutant phenotypes permitting somatic evolution of cancer. The model demonstrates carcinogenesis is an emergent phenomenon requiring a sequence of evolutionary steps as cellular proliferation follows successful adaptation to varying environmental constraints. In the initial development of preneoplastic lesions, cellular proliferation is controlled exclusively by interactions with other cells, the extracellular matrix, and soluble or insoluble growth factors so that gain of function mutations in oncogenes, loss of function mutations in tumor suppressor genes, and disruption of normal senescence pathways will permit clonal expansion. This provides explicit selection mechanisms for the mutations depicted in the classical Fearon-Vogelstein model of colorectal carcinogenesis. The model demonstrates neoplastic cellular proliferation can also be promoted by alterations in the somatic landscape that reduce inhibitory signals produced by the normal cells and extracellular matrix. This is consistent with experimental evidence for a strong microenvironmental influence in tumorigenesis independent of genomic changes in the neoplastic populations. However, we find that these changes alone produce only self-limited neoplastic growth because cellular crowding alters system dynamics so that proliferation is dependent on substrate availability. Consequent cellular competition for critical nutrients results in Darwinian selection pressures favoring phenotypes that increase substrate delivery (e.g., angiogenesis) or uptake (e.g., amplify membrane transporters). These previously unknown substrate dynamics in the later stages of carcinogenesis provide a mechanism for evolution of cellular properties typically found in invasive cancers including the angiogenic and glycolytic phenotypes.}, } @article {pmid14529745, year = {2003}, author = {Bosch, TC}, title = {Ancient signals: peptides and the interpretation of positional information in ancestral metazoans.}, journal = {Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology}, volume = {136}, number = {2}, pages = {185-196}, doi = {10.1016/s1096-4959(03)00226-4}, pmid = {14529745}, issn = {1096-4959}, mesh = {Animals ; Biological Evolution ; *Body Patterning ; Cnidaria/embryology/genetics ; Invertebrates/*embryology/genetics ; Peptides/genetics/*metabolism ; *Signal Transduction ; }, abstract = {Understanding the 'tool kit' that builds the most fundamental aspects of animal complexity requires data from the basal animals. Among the earliest diverging animal phyla are the Cnidaria which are the first in having a defined body plan including an axis, a nervous system and a tissue layer construction. Here I revise our understanding of patterning mechanism in cnidarians with special emphasis on the nature of positional signals in Hydra as perhaps the best studied model organism within this phylum. I show that (i) peptides play a major role as positional signals and in cell-cell communication; (ii) that intracellular signalling pathways in Hydra leading to activation of target genes are shared with all multicellular animals; (iii) that homeobox genes translate the positional signals; and (iv) that the signals are integrated by a complex genetic regulatory machinery that includes both novel cis regulatory elements as well as taxon specific target genes. On the basis of these results I present a model for the regulatory interactions required for axis formation in Hydra.}, } @article {pmid14520878, year = {2003}, author = {Shpakov, AO and Derkach, KV and Pertseva, MN}, title = {[Hormonal signal system of the lower eukaryotes].}, journal = {Tsitologiia}, volume = {45}, number = {3}, pages = {223-234}, pmid = {14520878}, issn = {0041-3771}, mesh = {Adenylyl Cyclases/chemistry/metabolism ; Amino Acid Sequence ; Biological Evolution ; Eukaryotic Cells/enzymology/metabolism/*physiology ; GTP-Binding Proteins/chemistry/metabolism ; Guanylate Cyclase/chemistry/metabolism ; Hormones/*physiology ; Molecular Sequence Data ; Sequence Alignment ; Signal Transduction/*physiology ; }, abstract = {The literary and the authors' own data on the structural and functional organization of hormonal signaling systems in the lower eukaryotes (yeasts, trypanosomes, ciliates, slide mold Dictyostelium discoideum) have been summarized and analysed. On the basis of a comparative analysis of the primary structures of signal proteins in the lower and higher eukaryotes (G-protein alpha-subunits, enzymes-cyclases-adenylyl and guanylyl cyclases) some possible pathways of the evolution of proteins are suggested. At the level of unicellular organisms, the main blocks of hormone-sensitive signaling systems of the higher eukaryotes were created. Moreover, signaling systems of the lower eukaryotes ar more invariant than these of the higher eukaryotes. It may be associated with the fact that of functional blocks, typical for signaling systems of multicellular animals, fungi and plants, were selected from the numerous variants of signaling system blocks of unicellular organisms.}, } @article {pmid14518551, year = {2003}, author = {Hallmann, A}, title = {Extracellular matrix and sex-inducing pheromone in Volvox.}, journal = {International review of cytology}, volume = {227}, number = {}, pages = {131-182}, doi = {10.1016/s0074-7696(03)01009-x}, pmid = {14518551}, issn = {0074-7696}, mesh = {Amino Acid Sequence ; Animals ; Extracellular Matrix/*physiology ; Glycoproteins/metabolism ; Molecular Sequence Data ; Sex Attractants/*genetics/*metabolism ; Volvox/*physiology ; }, abstract = {During evolution of multicellularity it was imperative to create a complex, multifunctional extracellular matrix (ECM) out of the simple cell wall of a unicellular ancestor. The green alga Volvox represents one of the simplest multicellular organisms, but even so, it already has a highly developed ECM. This ECM is mainly composed of an assortment of glycoproteins, many of which are hydroxyproline rich and extensively sulfated. Several ECM proteins are cross-linked and might have only structural functions. However, the ECM does not represent a static but rather a dynamic and multifunctional interface between a cell and its neighboring cells or its environment. It not only provides protection and structural support for the shape of each cell and the organism as a whole, but also plays a broad range of biological roles in growth, development, reproduction, and responses to environmental stress or wounding. The variety of functions of the ECM requires many glycoproteins to do the work. To attain a high flexibility and adaptability, almost all ECM glycoproteins from Volvox consist of modules, defined as functional subunits that form modular mosaic proteins with an outstanding combinatorial potential. The ECM's functions are not only extensive but also change under developmental control or by environmental incidents. The changing scope of duties necessitates a permanent ECM turnover and remodeling. In Volvox carteri one particularly challenging trigger of such ECM modifications is a sex-inducing pheromone, which is one of the most potent biological effector molecules known: the glycoprotein pheromone is fully effective for inducing sexual development in males and females at concentrations as low as 10(-16) M. The earliest detectable response to the pheromone is the synthesis of ECM glycoproteins.}, } @article {pmid14516695, year = {2002}, author = {Tanaka, SS and Matsui, Y}, title = {Developmentally regulated expression of mil-1 and mil-2, mouse interferon-induced transmembrane protein like genes, during formation and differentiation of primordial germ cells.}, journal = {Mechanisms of development}, volume = {119 Suppl 1}, number = {}, pages = {S261-7}, doi = {10.1016/s0925-4773(03)00126-6}, pmid = {14516695}, issn = {0925-4773}, mesh = {Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism ; *Gene Expression Regulation, Developmental ; Germ Cells/metabolism ; Humans ; *Interferon Inducers ; Interferons ; Mice ; }, abstract = {In all multicellular organisms, germ cells originating from a fertilized egg have the highly specialized role of transmitting genetic information to the next generation. In many animal species, the establishment of the germ cell lineage is regulated by the maternally inherited germplasm. In mammals, however, germline determination is not based on the unequal distribution of maternal determinants. In the processes of mammalian germ cell formation and subsequent differentiation, the molecular basis of the acquisition of germ cell status is not well understood. Since migrating primordial germ cells (PGCs) are lineage-restricted to the germline, they have already acquired a germ cell specific fate distinct from that of pluri/multi-potent stem cells. However, there have been no molecules known to be expressed in migrating PGCs but not in the inner cell mass of blastocysts. Such molecules should be involved in early germ cell development, and they should make good markers for following the process of PGC formation. To identify such molecules, we performed a subtracted cDNA screening with migrating PGCs and blastocysts in mice, and isolated 11 clones preferentially expressed in PGCs. Here, we report the identification of two genes with similarity to human interferon-induced transmembrane protein (Ifitm) genes, and expression patterns of these genes in forming and in differentiating PGCs. During germ cell formation, mouse Ifitm like (mil)-1 was expressed in putative PGC ancestors in embryos at 6.5-7.5 days post coitum. In migrating PGCs, mil-1 expression was continuously observed and mil-2 expression was first detected during germ cell differentiation.}, } @article {pmid14505573, year = {2003}, author = {Colombani, J and Raisin, S and Pantalacci, S and Radimerski, T and Montagne, J and Léopold, P}, title = {A nutrient sensor mechanism controls Drosophila growth.}, journal = {Cell}, volume = {114}, number = {6}, pages = {739-749}, doi = {10.1016/s0092-8674(03)00713-x}, pmid = {14505573}, issn = {0092-8674}, mesh = {Amino Acid Transport Systems/deficiency/genetics/*isolation & purification/metabolism ; Amino Acids/deficiency ; Animals ; Down-Regulation/physiology ; Drosophila Proteins/deficiency/genetics/*isolation & purification/metabolism ; Drosophila melanogaster/cytology/*growth & development/metabolism ; Fat Body/metabolism ; Feedback, Physiological/genetics ; Food Deprivation/*physiology ; Gene Expression Regulation, Developmental/genetics ; Juvenile Hormones/deficiency/*isolation & purification/metabolism ; Nutritional Physiological Phenomena/*physiology ; Phosphatidylinositol 3-Kinases/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism ; Signal Transduction/physiology ; }, abstract = {Organisms modulate their growth according to nutrient availability. Although individual cells in a multicellular animal may respond directly to nutrient levels, growth of the entire organism needs to be coordinated. Here, we provide evidence that in Drosophila, coordination of organismal growth originates from the fat body, an insect organ that retains endocrine and storage functions of the vertebrate liver. In a genetic screen for growth modifiers, we identified slimfast, a gene that encodes an amino acid transporter. Remarkably, downregulation of slimfast specifically within the fat body causes a global growth defect similar to that seen in Drosophila raised under poor nutritional conditions. This involves TSC/TOR signaling in the fat body, and a remote inhibition of organismal growth via local repression of PI3-kinase signaling in peripheral tissues. Our results demonstrate that the fat body functions as a nutrient sensor that restricts global growth through a humoral mechanism.}, } @article {pmid14505434, year = {2003}, author = {Grenier, G and Remy-Zolghadri, M and Guignard, R and Bergeron, F and Labbe, R and Auger, FA and Germain, L}, title = {Isolation and culture of the three vascular cell types from a small vein biopsy sample.}, journal = {In vitro cellular & developmental biology. Animal}, volume = {39}, number = {3-4}, pages = {131-139}, pmid = {14505434}, issn = {1071-2690}, mesh = {Animals ; Cell Culture Techniques/methods ; Coloring Agents ; Dogs ; Endothelium, Vascular/*cytology ; Fibroblasts/cytology ; Humans ; Jugular Veins/*cytology ; Kinetics ; Muscle, Smooth, Vascular/*cytology ; Saphenous Vein/*cytology ; Time Factors ; }, abstract = {The availability of small-diameter blood vessels remains a significant problem in vascular reconstruction. In small-diameter blood vessels, synthetic grafts resulted in low patency; the addition of endothelial cells (EC) has clearly improved this parameter, thereby proving the important contribution of the cellular component to the functionality of any construct. Because the optimal source of cells should be autologous, the adaptation of existing methods for the isolation of all the vascular cell types present in a single and small biopsy sample, thus reducing patient's morbidity, is a first step toward future clinical applications of any newly developed tissue-engineered blood vessel. This study describes such a cell-harvesting procedure from vein biopsy samples of canine and human origin. For this purpose, we combined preexisting mechanical methods for the isolation of the three vascular cell types: EC by scraping of the endothelium using a scalpel blade, vascular smooth muscle cells (VSMC), and perivascular fibroblasts according to the explant method. Once in culture, cells rapidly grew with the high level of enrichment. The morphological, phenotypical, and functional expected criteria were maintained: EC formed cobblestone colonies, expressed the von Willebrand factor, and incorporated acetylated low-density lipoprotein (LDL); VSMC were elongated and contracted when challenged by vasoactive agents; perivascular fibroblasts formed a mechanically resistant structure. Thus, we demonstrated that an appropriate combination of preexisting harvesting methods is suitable to isolate simultaneously the vascular cell types present in a single biopsy sample. Their functional characteristics indicated that they were suitable for the cellularization of synthetic prosthesis or the reconstruction of functional multicellular autologous organs by tissue engineering.}, } @article {pmid13678526, year = {2003}, author = {Dixon, DP and Van Lith, M and Edwards, R and Benham, A}, title = {Cloning and initial characterization of the Arabidopsis thaliana endoplasmic reticulum oxidoreductins.}, journal = {Antioxidants & redox signaling}, volume = {5}, number = {4}, pages = {389-396}, doi = {10.1089/152308603768295122}, pmid = {13678526}, issn = {1523-0864}, mesh = {Arabidopsis/*genetics ; Arabidopsis Proteins/*genetics/metabolism ; Base Sequence ; Cell Line ; Cloning, Molecular ; Exons/genetics ; Genes, Plant/genetics ; Glycoproteins/chemistry/*genetics/*metabolism ; Glycosylation ; Humans ; Introns/genetics ; Membrane Glycoproteins/*genetics/metabolism ; Molecular Sequence Data ; Oxidoreductases ; Oxidoreductases Acting on Sulfur Group Donors ; Phylogeny ; *Saccharomyces cerevisiae Proteins ; Sequence Alignment ; }, abstract = {The oxidation and isomerization of disulfide bonds is necessary for the growth of all organisms. In yeast, the oxidative folding of secretory pathway proteins is catalyzed by protein disulfide isomerase (PDI), which requires Ero1p (endoplasmic reticulum oxidoreductin) for its own oxidation. In Homo sapiens, two homologues of Ero1p, Ero1-Lalpha and Ero1-Lbeta, have been cloned. Both Ero1-Lalpha and Ero1-Lbeta interact via disulfide bonds with PDI and support the oxidation of immunoglobulin light chains. However, the function of Ero proteins in plants has not yet been analyzed. In this article, we report the cloning of the two Ero1p homologues present in Arabidopsis thaliana, demonstrating that one of the cDNAs has a shorter terminal exon than predicted and differs from the annotated sequence found in the genome database. Sequence analysis of the Arabidopsis endoplasmic reticulum oxidoreductins (AEROs) reveals that both AERO1 and AERO2 are more closely related to each other than to either of the human Eros. Both in vitro translated AERO proteins are targeted to the endoplasmic reticulum and glycosylated. The ability to use a genetically tractable multicellular organism in combination with biochemical approaches should further our understanding of redox networks and Ero function in both plants and animals.}, } @article {pmid13678422, year = {2003}, author = {Prag, S and Adams, JC}, title = {Molecular phylogeny of the kelch-repeat superfamily reveals an expansion of BTB/kelch proteins in animals.}, journal = {BMC bioinformatics}, volume = {4}, number = {}, pages = {42}, pmid = {13678422}, issn = {1471-2105}, mesh = {Amino Acid Motifs/genetics ; Amino Acid Sequence/genetics ; Animals ; Anopheles/genetics ; Caenorhabditis elegans Proteins/chemistry/genetics ; Carrier Proteins/*chemistry/*genetics ; DNA Repeat Expansion/*genetics ; Drosophila Proteins/chemistry/genetics ; Evolution, Molecular ; Genome, Fungal ; Genome, Human ; Genome, Protozoan ; Humans ; Mice ; Molecular Sequence Data ; *Multigene Family ; *Phylogeny ; Poxviridae/genetics ; Rats ; Saccharomyces cerevisiae Proteins/chemistry/genetics ; Schizosaccharomyces pombe Proteins/chemistry/genetics ; Sequence Alignment/methods ; Viral Proteins/chemistry/genetics ; }, abstract = {BACKGROUND: The kelch motif is an ancient and evolutionarily-widespread sequence motif of 44-56 amino acids in length. It occurs as five to seven repeats that form a beta-propeller tertiary structure. Over 28 kelch-repeat proteins have been sequenced and functionally characterised from diverse organisms spanning from viruses, plants and fungi to mammals and it is evident from expressed sequence tag, domain and genome databases that many additional hypothetical proteins contain kelch-repeats. In general, kelch-repeat beta-propellers are involved in protein-protein interactions, however the modest sequence identity between kelch motifs, the diversity of domain architectures, and the partial information on this protein family in any single species, all present difficulties to developing a coherent view of the kelch-repeat domain and the kelch-repeat protein superfamily. To understand the complexity of this superfamily of proteins, we have analysed by bioinformatics the complement of kelch-repeat proteins encoded in the human genome and have made comparisons to the kelch-repeat proteins encoded in other sequenced genomes.

RESULTS: We identified 71 kelch-repeat proteins encoded in the human genome, whereas 5 or 8 members were identified in yeasts and around 18 in C. elegans, D. melanogaster and A. gambiae. Multiple domain architectures were identified in each organism, including previously unrecognised forms. The vast majority of kelch-repeat domains are predicted to form six-bladed beta-propellers. The most prevalent domain architecture in the metazoan animal genomes studied was the BTB/kelch domain organisation and we uncovered 3 subgroups of human BTB/kelch proteins. Sequence analysis of the kelch-repeat domains of the most robustly-related subgroups identified differences in beta-propeller organisation that could provide direction for experimental study of protein-binding characteristics.

CONCLUSION: The kelch-repeat superfamily constitutes a distinct and evolutionarily-widespread family of beta-propeller domain-containing proteins. Expansion of the family during the evolution of multicellular animals is mainly accounted for by a major expansion of the BTB/kelch domain architecture. BTB/kelch proteins constitute 72 % of the kelch-repeat superfamily of H. sapiens and form three subgroups, one of which appears the most-conserved during evolution. Distinctions in propeller blade organisation between subgroups 1 and 2 were identified that could provide new direction for biochemical and functional studies of novel kelch-repeat proteins.}, } @article {pmid12975617, year = {2002}, author = {Lin, X and Perrimon, N}, title = {Developmental roles of heparan sulfate proteoglycans in Drosophila.}, journal = {Glycoconjugate journal}, volume = {19}, number = {4-5}, pages = {363-368}, pmid = {12975617}, issn = {0282-0080}, support = {GM63891-01A1/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Body Patterning ; Drosophila/genetics/*growth & development/physiology ; Drosophila Proteins/physiology ; Evolution, Molecular ; Genes, Insect ; Hedgehog Proteins ; Heparan Sulfate Proteoglycans/genetics/*physiology ; Models, Biological ; Mutation ; Proto-Oncogene Proteins/physiology ; Signal Transduction ; Wnt Proteins ; *Zebrafish Proteins ; }, abstract = {The formation of complex patterns in multi-cellular organisms is regulated by a number of signaling pathways. In particular, the Wnt and Hedgehog (Hh) pathways have been identified as critical organizers of pattern in many tissues. Although extensive biochemical and genetic studies have elucidated the central components of the signal transduction pathways regulated by these secreted molecules, we still do not understand fully how they organize gradients of gene activities through field of cells. Studies in Drosophila have implicated a role for heparan sulfate proteoglycans (HSPGs) in regulating the signaling activities and distribution of both Wnt and Hh. Here we review these findings and discuss various models by which HSPGs regulate the distributions of Wnt and Hh morphogens.}, } @article {pmid12975325, year = {2003}, author = {Sharp, JA and Krawitz, DC and Gardner, KA and Fox, CA and Kaufman, PD}, title = {The budding yeast silencing protein Sir1 is a functional component of centromeric chromatin.}, journal = {Genes & development}, volume = {17}, number = {19}, pages = {2356-2361}, pmid = {12975325}, issn = {0890-9369}, support = {R01 GM055712/GM/NIGMS NIH HHS/United States ; }, mesh = {Calcium-Binding Proteins/genetics/metabolism ; *Carrier Proteins ; Cell Cycle Proteins ; Centromere/genetics/*metabolism ; Chromatin/*metabolism ; Chromatin Assembly Factor-1 ; *Chromosomal Proteins, Non-Histone ; Chromosome Segregation ; DNA-Binding Proteins/genetics/metabolism ; Fungal Proteins/genetics/metabolism ; Kinetochores/physiology ; Mad2 Proteins ; Nuclear Proteins/genetics/metabolism ; Protein Subunits ; Recombinant Fusion Proteins/genetics/metabolism ; Repressor Proteins/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Saccharomycetales/*genetics ; Silent Information Regulator Proteins, Saccharomyces cerevisiae/genetics/*metabolism ; }, abstract = {In fission yeast and multicellular organisms, centromere-proximal regions of chromosomes are heterochromatic, containing proteins that silence gene expression. In contrast, the relationship between heterochromatin proteins and kinetochore function in the budding yeast Saccharomyces cerevisiae remains largely unexplored. Here we report that the yeast heterochromatin protein Sir1 is a component of centromeric chromatin and contributes to mitotic chromosome stability. Sir1 recruitment to centromeres occurred through a novel mechanism independent of its interaction with the origin recognition complex (ORC). Sir1 function at centromeres was distinct from its role in forming heterochromatin, because the Sir2-4 proteins were not associated with centromeric regions. Sir1 bound to Cac1, a subunit of chromatin assembly factor I (CAF-I), and helped to retain Cac1 at centromeric loci. These studies reveal that although budding yeast and mammalian cells use fundamentally different mechanisms of forming heterochromatin, they both use silencing proteins to attract the histone deposition factor CAF-I to centromeric chromatin.}, } @article {pmid12975308, year = {2003}, author = {Fedorov, A and Roy, S and Fedorova, L and Gilbert, W}, title = {Mystery of intron gain.}, journal = {Genome research}, volume = {13}, number = {10}, pages = {2236-2241}, pmid = {12975308}, issn = {1088-9051}, mesh = {Animals ; Arabidopsis/genetics ; Base Sequence ; Caenorhabditis elegans/genetics ; Computational Biology/methods ; Drosophila melanogaster/genetics ; Evolution, Molecular ; Gene Duplication ; Genes, Helminth/genetics ; Genes, Insect/genetics ; Humans ; Introns/*genetics ; Molecular Sequence Data ; Recombination, Genetic/genetics ; Sequence Homology, Nucleic Acid ; }, abstract = {For nearly 15 years, it has been widely believed that many introns were recently acquired by the genes of multicellular organisms. However, the mechanism of acquisition has yet to be described for a single animal intron. Here, we report a large-scale computational analysis of the human, Drosophila melanogaster, Caenorhabditis elegans, and Arabidopsis thaliana genomes. We divided 147,796 human intron sequences into batches of similar lengths and aligned them with each other. Different types of homologies between introns were found, but none showed evidence of simple intron transposition. Also, 106,902 plant, 39,624 Drosophila, and 6021 C. elegans introns were examined. No single case of homologous introns in nonhomologous genes was detected. Thus, we found no example of transposition of introns in the last 50 million years in humans, in 3 million years in Drosophila and C. elegans, or in 5 million years in Arabidopsis. Either new introns do not arise via transposition of other introns or intron transposition must have occurred so early in evolution that all traces of homology have been lost.}, } @article {pmid12971717, year = {2003}, author = {Biamonti, G and Paixão, S and Montecucco, A and Peverali, FA and Riva, S and Falaschi, A}, title = {Is DNA sequence sufficient to specify DNA replication origins in metazoan cells?.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {11}, number = {5}, pages = {403-412}, pmid = {12971717}, issn = {0967-3849}, mesh = {Animals ; Base Sequence/*genetics ; Cell Cycle/*physiology ; Chromatin/*genetics ; DNA Replication/*genetics ; DNA-Binding Proteins/*genetics/metabolism ; Origin Recognition Complex ; Plants ; Replication Origin/*genetics ; }, abstract = {DNA replication occupies a central position in the cell cycle and, therefore, in the development and life of multicellular organisms. During the last 10 years, our comprehension of this important process has considerably improved. Although the mechanisms that coordinate DNA replication with the other moments of the cell cycle are not yet fully understood, it is known that they mainly operate through DNA replication origins and the protein complexes bound to them. In eukaryotes, the packaging status of chromatin seems to be part of the mechanism that controls whether or not and when during the S-phase a particular origin will be activated. Intriguingly, the protein complexes bound to DNA replication origins appear to be directly involved in controlling chromatin packaging. In this manner they can also affect gene expression. In this review we focus on DNA replication origins in metazoan cells and on the relationship between these elements and the structural and functional organization of the genome.}, } @article {pmid12965020, year = {2003}, author = {Fiegna, F and Velicer, GJ}, title = {Competitive fates of bacterial social parasites: persistence and self-induced extinction of Myxococcus xanthus cheaters.}, journal = {Proceedings. Biological sciences}, volume = {270}, number = {1523}, pages = {1527-1534}, pmid = {12965020}, issn = {0962-8452}, mesh = {Biological Evolution ; Colony Count, Microbial ; Microbial Viability ; Movement ; Myxococcus xanthus/growth & development/*physiology ; Spores, Bacterial/physiology ; }, abstract = {Cooperative biological systems are susceptible to disruption by cheating. Using the social bacterium Myxococcus xanthus, we have tested the short-term competitive fates of mixed cheater and wild-type strains over multiple cycles of cooperative development. Cheater/wild-type mixes underwent several cycles of starvation-induced multicellular development followed by spore germination and vegetative population growth. The population sizes of cheater and wild-type strains in each pairwise mixture were measured at the end of each developmental phase and each growth phase. Cheater genotypes showed several distinct competitive fates, including cheater persistence at high frequencies with little effect on total population dynamics, cheater persistence after major disruption of total population dynamics, self-extinction of cheaters with wild-type survival, and total population extinction. Our results empirically demonstrate that social exploitation can destabilize a cooperative biological system and increase the risk of local extinction events.}, } @article {pmid12957942, year = {2003}, author = {Greub, G and Raoult, D}, title = {History of the ADP/ATP-translocase-encoding gene, a parasitism gene transferred from a Chlamydiales ancestor to plants 1 billion years ago.}, journal = {Applied and environmental microbiology}, volume = {69}, number = {9}, pages = {5530-5535}, pmid = {12957942}, issn = {0099-2240}, mesh = {Base Sequence ; Chlamydiales/classification/*enzymology/*genetics ; DNA Primers ; Eukaryota/enzymology/genetics ; *Evolution, Molecular ; Mitochondrial ADP, ATP Translocases/*genetics ; Phylogeny ; Plants/enzymology/genetics ; Polymerase Chain Reaction/methods ; Rickettsiaceae/enzymology/genetics ; Time Factors ; }, abstract = {Nonmitochondrial ADP/ATP translocase is an energy parasite enzyme. Its encoding gene, tlc, is found only in Rickettsiales, Chlamydiales, and plant and alga plastids. We demonstrate the presence of tlc in Parachlamydia acanthamoebae. This gene shares more similarity with the tlc1 gene of Chlamydiaceae and the tlc of plant and alga plastids than with the tlc2 gene of Chlamydiaceae. Phylogenetic analysis, including all other tlc homologs found in GenBank, showed that tlc was duplicated in a Chlamydiales ancestor before the appearance of multicellular eukaryotes. A time scale, calibrated with seven independent time points obtained from fossil estimates and from the 16S rRNA molecular clock, was congruent with the molecular clock provided by tlc. Plant and alga plastids acquired tlc approximately when Parachlamydiaceae and Chlamydiaceae diverged, at the eucaryotic radiation time, ca. 1 billion years ago.}, } @article {pmid12955143, year = {2003}, author = {Velicer, GJ and Yu, YT}, title = {Evolution of novel cooperative swarming in the bacterium Myxococcus xanthus.}, journal = {Nature}, volume = {425}, number = {6953}, pages = {75-78}, doi = {10.1038/nature01908}, pmid = {12955143}, issn = {1476-4687}, mesh = {Antigens, Bacterial/genetics/metabolism ; Bacterial Adhesion/genetics/physiology ; *Biological Evolution ; Cell Aggregation ; Fimbriae, Bacterial/genetics/metabolism ; Genes, Bacterial/genetics ; *Models, Biological ; Mutation/genetics ; Myxococcus xanthus/*cytology/genetics/*physiology ; Social Behavior ; }, abstract = {Cooperation among individuals is necessary for evolutionary transitions to higher levels of biological organization. In such transitions, groups of individuals at one level (such as single cells) cooperate to form selective units at a higher level (such as multicellular organisms). Though the evolution of cooperation is difficult to observe directly in higher eukaryotes, microorganisms do offer such an opportunity. Here we report the evolution of novel cooperative behaviour in experimental lineages of the bacterium Myxococcus xanthus. Wild-type strains of M. xanthus exhibit socially dependent swarming across soft surfaces by a mechanism known as 'S-motility' that requires the presence of extracellular type IV pili. In lineages of M. xanthus unable to make pili, a new mechanistic basis for cooperative swarming evolved. Evolved swarming is mediated, at least in part, by enhanced production of an extracellular fibril matrix that binds cells-and their evolutionary interests-together. Though costly to individuals, fibril production greatly enhanced population expansion in groups of interconnected cells. These results show that fundamental transitions to primitive cooperation can readily occur in bacteria.}, } @article {pmid12955142, year = {2003}, author = {Rainey, PB and Rainey, K}, title = {Evolution of cooperation and conflict in experimental bacterial populations.}, journal = {Nature}, volume = {425}, number = {6953}, pages = {72-74}, doi = {10.1038/nature01906}, pmid = {12955142}, issn = {1476-4687}, mesh = {Bacterial Adhesion/genetics/physiology ; *Biological Evolution ; Biopolymers/biosynthesis/genetics ; Cell Aggregation ; Genotype ; *Models, Biological ; Mutation/genetics ; Pseudomonas fluorescens/*cytology/genetics/*physiology ; Social Behavior ; }, abstract = {A fundamental problem in biology is the evolutionary transition from single cells to multicellular life forms. During this transition the unit of selection shifts from individual cells to groups of cooperating cells. Although there is much theory, there are few empirical studies. Here we describe an evolutionary transition that occurs in experimental populations of Pseudomonas fluorescens propagated in a spatially heterogeneous environment. Cooperating groups are formed by over-production of an adhesive polymer, which causes the interests of individuals to align with those of the group. The costs and benefits of cooperation, plus evolutionary susceptibility to defecting genotypes, were analysed to determine conformation to theory. Cooperation was costly to individuals, but beneficial to the group. Defecting genotypes evolved in populations founded by the cooperating type and were fitter in the presence of this type than in its absence. In the short term, defectors sabotaged the viability of the group; but these findings nevertheless show that transitions to higher orders of complexity are readily achievable, provide insights into the selective conditions, and facilitate experimental analysis of the evolution of individuality.}, } @article {pmid12952677, year = {2003}, author = {Ziman, J}, title = {Emerging out of nature into history: the plurality of the sciences.}, journal = {Philosophical transactions. Series A, Mathematical, physical, and engineering sciences}, volume = {361}, number = {1809}, pages = {1617-1633}, doi = {10.1098/rsta.2003.1233}, pmid = {12952677}, issn = {1364-503X}, mesh = {Adaptation, Physiological ; *Biological Evolution ; *Knowledge ; *Models, Theoretical ; *Nature ; Science/*trends ; }, abstract = {The idea of a 'theory of everything' is inconsistent with a natural feature of biological evolution: the spontaneous emergence of composite entities with completely new properties. At successively higher levels of complexity, from elementary particles and chemical molecules, through unicellular and multicellular organisms, to self-aware human beings and their cultural institutions, we find systems obeying entirely novel principles. The behaviour of such systems is not predictable from the properties of their constituents, so distinct 'languages' are required to describe them scientifically. The plurality of our sciences is thus an irreducible feature of the universe we live in. In particular, the reversible time coordinate of mathematical physics cannot cope with the natural 'path dependence' of biology. In the human sciences this extends into the imagined future as well as the remembered past. Furthermore, science nowadays usually arises in localized social contexts, where the 'logic of the situation' is continually being transformed by the emergence of cultural novelties such as unpredictable technological innovations. Thus, scientific knowledge cannot be restricted to generalized synchronic models, but involves historical narratives of specific events and unforeseen circumstances.}, } @article {pmid12949148, year = {2003}, author = {Kofuji, R and Sumikawa, N and Yamasaki, M and Kondo, K and Ueda, K and Ito, M and Hasebe, M}, title = {Evolution and divergence of the MADS-box gene family based on genome-wide expression analyses.}, journal = {Molecular biology and evolution}, volume = {20}, number = {12}, pages = {1963-1977}, doi = {10.1093/molbev/msg216}, pmid = {12949148}, issn = {0737-4038}, mesh = {Arabidopsis/*genetics/metabolism ; *Evolution, Molecular ; Gene Expression Profiling/methods ; *Genetic Variation ; Genome, Plant ; MADS Domain Proteins/*genetics/metabolism ; Multigene Family ; Phylogeny ; Pollen/genetics/metabolism ; }, abstract = {MADS-box genes encode transcription factors involved in various important aspects of development and differentiation in land plants, metazoans, and other organisms. Three types of land plant MADS-box genes have been reported. MIKCC- and MIKC*-type genes both contain conserved MADS and K domains but have different exon/intron structures. M-type genes lack a K domain. Most MADS-box genes previously analyzed in land plants are expressed in the sporophyte (diploid plant body); few are expressed in the gametophyte (haploid plant body). Land plants are believed to have evolved from a gametophyte (haploid)-dominant ancestor without a multicellular sporophyte (diploid plant body); most genes expressed in the sporophyte probably originated from those used in the gametophyte during the evolution of land plants. To analyze the evolution and diversification of MADS-box genes in land plants, gametophytic MADS-box genes were screened using macroarray analyses for 105 MADS-box genes found in the Arabidopsis genome. Eight MADS-box genes were predominantly expressed in pollen, the male gametophyte; all but one of their expression patterns was confirmed by Northern analyses. Analyses of the exon/intron structure of these seven genes revealed that they included two MIKCC-type, one M-type, and four MIKC*-type MADS-box genes. Previously, MIKC*-type genes have been reported only from a moss and a club moss, and this is the first record in seed plants. These genes can be used to investigate the unknown ancestral functions of MADS-box genes in land plants. The macroarray analyses did not detect expression of 56 of 61 M-type MADS-box genes in any tissues examined. A phylogenetic tree including all three types of Arabidopsis MADS-box genes with representative genes from other organisms showed that M-type genes were polyphyletic and that their branch lengths were much longer than for the other genes. This finding suggests that most M-type genes are pseudogenes, although further experiments are necessary to confirm this possibility. Our global phylogenetic analyses of MADS-box genes did not support the previous classification of MADS-box genes into type I and II groups, based on smaller scale analyses. An evolutionary scenario for the evolution of MADS-box genes in land plants is discussed.}, } @article {pmid12949122, year = {2003}, author = {Aris-Brosou, S and Yang, Z}, title = {Bayesian models of episodic evolution support a late precambrian explosive diversification of the Metazoa.}, journal = {Molecular biology and evolution}, volume = {20}, number = {12}, pages = {1947-1954}, doi = {10.1093/molbev/msg226}, pmid = {12949122}, issn = {0737-4038}, mesh = {Algorithms ; Animals ; *Bayes Theorem ; Cell Nucleus/genetics ; Computer Simulation ; *Evolution, Molecular ; Fossils ; Invertebrates/*genetics ; Mitochondria/genetics ; Models, Genetic ; Phylogeny ; Time Factors ; }, abstract = {Multicellular animals, or Metazoa, appear in the fossil records between 575 and 509 million years ago (MYA). At odds with paleontological evidence, molecular estimates of basal metazoan divergences have been consistently older than 700 MYA. However, those date estimates were based on the molecular clock hypothesis, which is almost always violated. To relax this hypothesis, we have implemented a Bayesian approach to describe the change of evolutionary rate over time. Analysis of 22 genes from the nuclear and the mitochondrial genomes under the molecular clock assumption produced old date estimates, similar to those from previous studies. However, by allowing rates to vary in time and by taking small species-sampling fractions into account, we obtained much younger estimates, broadly consistent with the fossil records. In particular, the date of protostome-deuterostome divergence was on average 582 +/- 112 MYA. These results were found to be robust to specification of the model of rate change. The clock assumption thus had a dramatic effect on date estimation. However, our results appeared sensitive to the prior model of cladogenesis, although the oldest estimates (791 +/- 246 MYA) were obtained under a suboptimal model. Bayes posterior estimates of evolutionary rates indicated at least one major burst of molecular evolution at the end of the Precambrian when protostomes and deuterostomes diverged. We stress the importance of assumptions about rates on date estimation and suggest that the large discrepancies between the molecular and fossil dates of metazoan divergences might partly be due to biases in molecular date estimation.}, } @article {pmid12946356, year = {2003}, author = {Sherratt, MJ and Baldock, C and Haston, JL and Holmes, DF and Jones, CJ and Shuttleworth, CA and Wess, TJ and Kielty, CM}, title = {Fibrillin microfibrils are stiff reinforcing fibres in compliant tissues.}, journal = {Journal of molecular biology}, volume = {332}, number = {1}, pages = {183-193}, doi = {10.1016/s0022-2836(03)00829-5}, pmid = {12946356}, issn = {0022-2836}, mesh = {Aged ; Animals ; Cattle ; Cryoelectron Microscopy ; Deer ; Elasticity ; Elastin/chemistry ; Extracellular Matrix Proteins/chemistry/metabolism/ultrastructure ; Eye Proteins/chemistry/metabolism ; Fibrillins ; Humans ; Microfilament Proteins/*chemistry/metabolism/ultrastructure ; Microscopy, Atomic Force ; Models, Molecular ; Stress, Mechanical ; X-Ray Diffraction ; }, abstract = {Fibrillin-rich microfibrils have endowed tissues with elasticity throughout multicellular evolution. We have used molecular combing techniques to determine Young's modulus for individual microfibrils and X-ray diffraction of zonular filaments of the eye to establish the linearity of microfibril periodic extension. Microfibril periodicity is not altered at physiological zonular tissue extensions and Young's modulus is between 78 MPa and 96 MPa, which is two orders of magnitude stiffer than elastin. We conclude that elasticity in microfibril-containing tissues arises primarily from reversible alterations in supra-microfibrillar arrangements rather than from intrinsic elastic properties of individual microfibrils which, instead, act as reinforcing fibres in fibrous composite tissues.}, } @article {pmid12920563, year = {2003}, author = {Nikam, TD and Bansude, GM and Aneesh Kumar, KC}, title = {Somatic embryogenesis in sisal (Agave sisalana Perr. ex. Engelm).}, journal = {Plant cell reports}, volume = {22}, number = {3}, pages = {188-194}, doi = {10.1007/s00299-003-0675-9}, pmid = {12920563}, issn = {0721-7714}, mesh = {Agave/*embryology/growth & development/physiology ; Plant Roots/growth & development/physiology ; Plant Shoots/growth & development/physiology ; Plant Structures/growth & development/physiology ; Regeneration ; }, abstract = {A protocol has been developed for somatic embryogenesis and plant regeneration of sisal (Agave sisalana Perr. ex. Engelm). Embryogenic callus cultures were initiated from young shoots raised in vitro from the stem portion of the bulbil on medium supplemented with 1-2 mg l(-1) kinetin (KN) and 0.2-0.5 mg l(-1) alpha-naphthaleneacetic acid plus KN or 1-1.5 mg l(-1)benzylaminopurine (BAP) or 0.25-0.5 mg l(-1)2,4-dichlorophenoxyacetic acid plus BAP or 0.5-1.0 mg l(-1) KN. Embryos at various developmental stages (globular-, heart- or torpedo-shaped) produced mature and germinating embryos on being transferred to a new medium containing 0-0.25 mg l(-1)KN. After 28 days, a maximum of 76% germinated embryos was obtained on a medium supplemented with 0.1 mg l(-1) KN. The capacity for embryogenesis remained constant in the callus upon subculturing on the same medium for more than 48 months. Histological observations showed a distinct multicellular origin for most of the somatic embryos as they developed from epidermal, sub-epidermal and inside callus cells, while a few of them originated from a superficial callus cell. Plantlets regenerated from embryos were transferred to the field where their survival rate was 100%.}, } @article {pmid12919822, year = {2003}, author = {Müller, WE and Korzhev, M and Le Pennec, G and Müller, IM and Schröder, HC}, title = {Origin of metazoan stem cell system in sponges: first approach to establish the model (Suberites domuncula).}, journal = {Biomolecular engineering}, volume = {20}, number = {4-6}, pages = {369-379}, doi = {10.1016/s1389-0344(03)00055-8}, pmid = {12919822}, issn = {1389-0344}, mesh = {Amino Acid Sequence ; Animals ; Carrier Proteins ; Cells, Cultured ; *Evolution, Molecular ; Ferric Compounds/pharmacology ; Gene Expression Profiling ; Gene Expression Regulation, Developmental/drug effects/*physiology ; Membrane Proteins/*chemistry/*genetics/metabolism ; Models, Animal ; Molecular Sequence Data ; *Phylogeny ; Porifera/drug effects/*genetics/*metabolism ; Proteins/*chemistry/*genetics/metabolism ; Sequence Analysis, Protein ; Sequence Homology, Amino Acid ; Silicates/pharmacology ; Stem Cells/drug effects/*metabolism ; }, abstract = {It is established that Porifera (sponges) represent the earliest phylum which branched off from the common ancestor of all multicellular animals, the Urmetazoa. In the present study, the hypothesis is tested if, during this transition, pluripotent stem cells were formed which are provided-similar to the totipotent cells (archaeocytes/germ cells)-with a self-renewal capacity. As a model system, primmorphs from the sponge Suberites domuncula were used. These 3D-cell aggregates were cultivated in medium (RPMI 1640/seawater) either lacking silicate and ferric iron or in medium which was supplemented with these 'morphogenetic' factors. As molecular markers for the potential existence of stem cells in primmorphs, two genes which encode proteins found in stem cells of higher metazoan species, were cloned from S. domuncula. First, the noggin gene, which is present in the Spemann organizer of amphibians and whose translation product acts during the formation of dorsal mesoderm derivatives. The second gene encodes the mesenchymal stem cell-like protein. Both cDNAs were used to study their expression in primmorphs in dependence on the incubation conditions. It was found that noggin expression is strongly upregulated in primmorphs kept in the presence of silicate and ferric iron, while the expression of the mesenchymal stem cell-like protein was downregulated. These data are discussed with respect to the existence of stem cells in sponges.}, } @article {pmid12917798, year = {2003}, author = {Hoenigsberg, H}, title = {Cell biology, molecular embryology, Lamarckian and Darwinian selection as evolvability.}, journal = {Genetics and molecular research : GMR}, volume = {2}, number = {1}, pages = {7-28}, pmid = {12917798}, issn = {1676-5680}, mesh = {Allergy and Immunology/history ; Animals ; B-Lymphocytes/immunology ; Cell Lineage ; DNA/biosynthesis ; *Evolution, Molecular ; Gene Rearrangement, B-Lymphocyte ; Genes, Immunoglobulin ; Genetics/history ; Germinal Center/immunology ; History, 19th Century ; History, 20th Century ; Models, Genetic ; Models, Immunological ; Mutation ; RNA/genetics ; *Selection, Genetic ; Somatic Hypermutation, Immunoglobulin ; Vertebrates/embryology/*genetics/immunology ; }, abstract = {The evolvability of vertebrate systems involves various mechanisms that eventually generate cooperative and nonlethal functional variation on which Darwinian selection can operate. It is a truism that to get vertebrate animals to develop a coherent machine they first had to inherit the right multicellular ontogeny. The ontogeny of a metazoan involves cell lineages that progressively deny their own capacity for increase and for totipotency in benefit of the collective interest of the individual. To achieve such cell altruism Darwinian dynamics rescinded its original unicellular mandate to reproduce. The distinction between heritability at the level of the cell lineage and at the level of the individual is crucial. However, its implications have seldom been explored in depth. While all out reproduction is the Darwinian measure of success among unicellular organisms, a high replication rate of cell lineages within the organism may be deleterious to the individual as a functional unit. If a harmoniously functioning unit is to evolve, mechanisms must have evolved whereby variants that increase their own replication rate by failing to accept their own somatic duties are controlled. For questions involving organelle origins, see Godelle and Reboud, 1995 and Hoekstra, 1990. In other words, modifiers of conflict that control cell lineages with conflicting genes and new mutant replication rates that deviate from their somatic duties had to evolve. Our thesis is that selection at the level of the (multicellular) individual must have opposed selection at the level of the cell lineage. The metazoan embryo is not immune to this conflict especially with the evolution of set-aside cells and other modes of self-policing modifiers (Blackstone and Ellison, 1998; Ransick et al., 1996. In fact, the conflict between the two selection processes permitted a Lamarckian soma-to-germline feedback loop. This new element in metazoan ontogeny became the evolvability of the vertebrate adaptive immune system and life as we know it now. We offer the hypothesis that metazoan evolution solved this ancient conflict by evolving an immunogenetic mechanism that responds with rapid Lamarckian efficiency by retaining the ancient reverse transcriptase enzyme (RNACopyright DNA copying discovered by Temin in 1959 (see Temin, 1989) and found in 1970 in RNA tumor viruses by Temin and Baltimore), which can produce cDNA from the genome of an RNA virus that infects the cells. It seems that molecular Lamarckism can survive (Lewin, 1993).}, } @article {pmid12915181, year = {2003}, author = {Hernandez, VP and Higgins, L and Schwientek, MS and Fallon, AM}, title = {The histone-like C-terminal extension in ribosomal protein S6 in Aedes and Anopheles mosquitoes is encoded within the distal portion of exon 3.}, journal = {Insect biochemistry and molecular biology}, volume = {33}, number = {9}, pages = {901-910}, doi = {10.1016/s0965-1748(03)00095-x}, pmid = {12915181}, issn = {0965-1748}, support = {AI 20385/AI/NIAID NIH HHS/United States ; }, mesh = {Aedes/chemistry/*genetics ; Amino Acid Sequence ; Animals ; Anopheles/chemistry/*genetics ; Base Sequence ; Cell Line ; DNA, Complementary/chemistry/genetics ; Drosophila/genetics ; Exons/*genetics ; Histones/*chemistry/genetics ; Introns/genetics ; Molecular Sequence Data ; Phylogeny ; Ribosomal Protein S6/chemistry/*genetics ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Ubiquitin/genetics ; }, abstract = {In eukaryotic cells, ribosomal protein S6 (RPS6) is the major phosphorylated protein on the small ribosomal subunit. In the mosquitoes Aedes aegypti and Aedes albopictus, the cDNA encoding RPS6 contains 300 additional nucleotides, relative to the Drosophila homolog. The additional sequence encodes a 100-amino acid, lysine-rich C-terminal extension of the RPS6 protein with 42-49% identity to histone H1 proteins from the chicken and other multicellular organisms. Using mass spectrometry we now show that the C-terminal extension predicted by the cDNA is present on RPS6 protein isolated from ribosomal subunits purified from Ae. albopictus cells. To expand our analysis beyond the genus Aedes, we cloned the rpS6 cDNA from an Anopheles stephensi mosquito cell line. The cDNA also encoded a lysine-rich C-terminal extension. However, in An. stephensi rpS6 the extension was approximately 70 amino acids longer than that in Ae. albopictus, and at the nucleotide level, it most closely resembled histone H1 proteins from the unicellular eukaryotes Leishmania and Chlamydomonas, and the bacterium Bordetella pertussis. To examine how the histone-like C-terminal extension is encoded in the genome, we used PCR-based approaches to obtain the genomic DNA sequence encoding Ae. aegypti and Ae. albopictus rpS6. The sequence encoding the histone-like C-terminal extension was contiguous with upstream coding sequence within a single open reading frame in Exon 3, indicating that the lysine-rich extension in mosquito RPS6 is not the result of an aberrant splicing event. An in silico investigation of the Anopheles gambiae genome based on the cDNA sequence from An. stephensi allowed us to map the An. gambiae gene to chromosome 2R, to deduce its exon-intron organization, and to confirm that Exon 3 encodes a C-terminal histone-like extension. Because the C-terminal extension is absent from Drosophila melanogaster, we examined a partial cDNA clone from a Psychodid fly, which shares a relatively recent common ancestor with the mosquitoes. The absence of the C-terminal extension in the Psychodid rpS6 cDNA suggests that the unusual RPS6 structure is restricted to a relatively small group of flies in the Nematocera.}, } @article {pmid12911623, year = {2003}, author = {Bouchard, C and Ribeiro, P and Dubé, F and Anctil, M}, title = {A new G protein-coupled receptor from a primitive metazoan shows homology with vertebrate aminergic receptors and displays constitutive activity in mammalian cells.}, journal = {Journal of neurochemistry}, volume = {86}, number = {5}, pages = {1149-1161}, doi = {10.1046/j.1471-4159.2003.01924.x}, pmid = {12911623}, issn = {0022-3042}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Biogenic Amines/metabolism ; Calcium Signaling ; Cell Line ; Cloning, Molecular ; Cnidaria/*metabolism ; GTP-Binding Proteins/metabolism ; Gene Expression ; Genes, Reporter ; Humans ; Kidney/cytology/metabolism ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; Receptors, Cell Surface/*genetics/*metabolism ; Sequence Homology, Amino Acid ; Signal Transduction/physiology ; Transfection ; Vertebrates ; }, abstract = {Biogenic amine receptors mediate wide-ranging hormonal and modulatory functions in vertebrates, but are largely unknown in primitive invertebrates. In a representative of the most basal multicellular animals possessing a nervous system, the cnidarian Renilla koellikeri, aminergic-like receptors were previously characterized pharmacologically and found to engender control of the animal's bioluminescent and peristaltic reactions. Using degenerate oligonucleotides in a RT-PCR strategy, we obtained a full-length cDNA encoding a polypeptide with typical G protein-coupled receptor (GPCR) characteristics and which displayed a significant degree of sequence similarity (up to 45%) to biogenic amine receptors, particularly dopamine and adrenergic receptors. The new receptor, named Ren1, did not resemble any one specific type of amine GPCR and thus could not be identified on the basis of sequence. Ren1 was expressed transiently and stably in cultured mammalian cells, as demonstrated by immunocytochemistry and western blotting. Functional analysis of transfected HEK293, LTK- and COS-7 cells, based on both cAMP and Ca2+ signalling assays, revealed that Ren1 was not activated by any of the known biogenic amines tested and several related metabolites. The results indicated, however, that cells stably expressing Ren1 contained, on average, an 11-fold higher level of cAMP than the controls, in the absence of agonist stimulation. The high basal cAMP levels were shown to be specific for Ren1 and to vary proportionally with the level of Ren1 expressed in the transfected cells. Taken together, the data suggested that Ren1 was expressed as a constitutively active receptor. Its identification provides a basis for examination of the early evolutionary emergence of GPCRs and their functional properties.}, } @article {pmid12908987, year = {2003}, author = {MacLean, RC and Bell, G}, title = {Divergent evolution during an experimental adaptive radiation.}, journal = {Proceedings. Biological sciences}, volume = {270}, number = {1524}, pages = {1645-1650}, pmid = {12908987}, issn = {0962-8452}, mesh = {*Adaptation, Biological ; *Biological Evolution ; Cluster Analysis ; Environment ; Genetic Drift ; Genetic Variation ; Mutation/genetics ; *Phenotype ; Pseudomonas fluorescens/*physiology ; Selection, Genetic ; }, abstract = {How repeatable a process is evolution? Comparative studies of multicellular eukaryotes and experimental studies with unicellular prokaryotes document the repeated evolution of adaptive phenotypes during similar adaptive radiations, suggesting that the outcome of adaptive radiation is broadly reproducible. The goal of this study was to test this hypothesis by using phenotypic traits to infer the genetic basis of adaptation to simple carbon-limited environments in an extensive adaptive radiation. We used a clone of the bacterium Pseudomonas fluorescens to found two sets of experimental lines. The first set of lines was allowed to adapt to one of 23 novel environments for 1100 generations while the second set of lines was allowed to accumulate mutations by drift for 2000 generations. All lines were then assayed in the 95 environments provided by Biolog microplates to determine the phenotypic consequences of selection and drift. Replicate selection lines propagated in a common environment evolved similar adaptive components of their phenotype but showed extensive variation in non-adaptive phenotypic traits. This variation in non-adaptive phenotypic traits primarily resulted from the ascendance of different beneficial mutations in different lines. We argue that these results reconcile experimental and comparative approaches to studying adaptation by demonstrating that the convergent phenotypic evolution that occurs during adaptive radiation may be associated with radically different sets of beneficial mutations.}, } @article {pmid12898249, year = {2003}, author = {Adell, T and Grebenjuk, VA and Wiens, M and Müller, WE}, title = {Isolation and characterization of two T-box genes from sponges, the phylogenetically oldest metazoan taxon.}, journal = {Development genes and evolution}, volume = {213}, number = {9}, pages = {421-434}, pmid = {12898249}, issn = {0949-944X}, mesh = {Alternative Splicing ; Amino Acid Sequence ; Animals ; Base Sequence ; DNA, Complementary ; Electrophoresis, Gel, Two-Dimensional ; Molecular Sequence Data ; Phylogeny ; Porifera/*genetics ; Protein Isoforms/genetics ; Protein Processing, Post-Translational ; Sequence Analysis, DNA ; T-Box Domain Proteins/*genetics ; }, abstract = {It is now well established that all metazoan phyla derived from one common ancestor, the hypothetical Urmetazoa. Due to the basal position of Porifera (Demospongiae) in the phylogenetic tree of Metazoa, studies on the mechanisms controlling the development of these animals can provide clues on the understanding of the origin of multicellular animals and on how the first organization of the body plan evolved. In this report we describe the isolation and genomic characterization of two T-box genes from the siliceous sponge Suberites domuncula. The phylogenetic analysis classifies one into the subfamily of Brachyury, Sd-Bra, and the second into the Tbx2 subfamily, Sd-Tbx2. Analyses of the Sd-Bra and Sd-Tbx2 sequences and their intron-exon structures demonstrate their basal position in the phylogeny of the T-box family, and allows us to hypothesize a model of the phylogenetic evolution of all T-box genes. Furthermore, we report the presence of two different products of alternative splicing of Sd-Bra, and demonstrate that they exist in different phosphorylation and glycosylation states in the sponge tissue. Sd-Bra expression in tissue and 3D-cell aggregates (primmorphs) is analyzed, suggesting that Sd-Bra might also have a role in Porifera morphogenesis.}, } @article {pmid12893743, year = {2003}, author = {Gaudesius, G and Miragoli, M and Thomas, SP and Rohr, S}, title = {Coupling of cardiac electrical activity over extended distances by fibroblasts of cardiac origin.}, journal = {Circulation research}, volume = {93}, number = {5}, pages = {421-428}, doi = {10.1161/01.RES.0000089258.40661.0C}, pmid = {12893743}, issn = {1524-4571}, mesh = {Animals ; Animals, Newborn ; Cell Communication/physiology ; Cells, Cultured ; Coculture Techniques/methods ; Connexin 43/analysis ; Connexins/analysis ; Electrophysiology ; Fibroblasts/cytology/*physiology ; HeLa Cells ; Heart Ventricles/cytology ; Humans ; Immunohistochemistry ; Intercellular Junctions/chemistry/physiology ; Microscopy, Video ; Myocytes, Cardiac/cytology/*physiology ; Rats ; Rats, Wistar ; *Ventricular Function ; }, abstract = {Roughly half of the cells of the heart consist of nonmyocardial cells, with fibroblasts representing the predominant cell type. It is well established that individual cardiomyocytes and fibroblasts in culture establish gap junctional communication at the single cell level (short-range interaction). However, it is not known whether such coupling permits activation of cardiac tissue over extended distances (long-range interaction). Long-range interactions may be responsible for electrical synchronization of donor and recipient tissue after heart transplantation and may play a role in arrhythmogenesis. This question was investigated using a novel heterocellular culture model with strands of cardiomyocytes interrupted by cardiac fibroblasts over defined distances. With use of optical recording techniques, it could be shown that impulse propagation along fibroblast inserts was successful over distances up to 300 microm and was characterized by length-dependent local propagation delays ranging from 11 to 68 ms (apparent local "conduction velocities" 4.6+/-1.8 mm/s, n=23). Involvement of mechanical stretch in this phenomenon was excluded by showing that inserts consisting of communication-deficient HeLa cells were incapable of supporting propagation. In contrast, HeLa cells expressing connexin43 permitted impulse conduction over distances as long as 600 microm. Immunocytochemistry showed that fibroblasts and cardiomyocytes expressed connexin43 and connexin45, whereas connexin40 was absent. These results illustrate that fibroblasts of cardiac origin are capable of synchronizing electrical activity of multicellular cardiac tissue over extended distances through electrotonic interactions. This synchronization is accompanied by extremely large local conduction delays, which might contribute to the generation of arrhythmias in fibrotic hearts.}, } @article {pmid12893638, year = {2003}, author = {Arutunyan, A and Pumir, A and Krinsky, V and Swift, L and Sarvazyan, N}, title = {Behavior of ectopic surface: effects of beta-adrenergic stimulation and uncoupling.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {285}, number = {6}, pages = {H2531-42}, pmid = {12893638}, issn = {0363-6135}, support = {R01 HL062419/HL/NHLBI NIH HHS/United States ; R01 HL062419-02/HL/NHLBI NIH HHS/United States ; R01 HL062419-03/HL/NHLBI NIH HHS/United States ; R01 HL062419-04/HL/NHLBI NIH HHS/United States ; }, mesh = {Adrenergic beta-Agonists/*pharmacology ; Animals ; Arrhythmias, Cardiac/*physiopathology ; Cell Communication/drug effects/physiology ; Cells, Cultured ; Gap Junctions/drug effects/physiology ; Heptanol/*pharmacology ; Isoproterenol/*pharmacology ; Isotonic Solutions/pharmacology ; Models, Biological ; Myocytes, Cardiac/cytology/*drug effects/*physiology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {By using both experimental and theoretical means, we have addressed the progression of ectopic activity from individual cardiac cells to a multicellular two-dimensional network. Experimental conditions that favor ectopic activity have been created by local perfusion of a small area of cardiomyocyte network (I-zone) with an isoproterenol-heptanol containing solution. The application of this solution initially slowed down and then fully blocked wave propagation inside the I-zone. After a brief lag period, ectopically active cells appeared in the I-zone, followed by evolution of the ectopic clusters into slowly propagating waves. The changing pattern of colliding and expanding ectopic waves confined to the I-zone persisted for as long as the isoproterenol-heptanol environment was present. On restoration of the control environment, the ectopic waves from the I-zone broke out into the surrounding network causing arrhythmias. The observed sequence of events was also modeled by FitzHugh-Nagumo equations and included a cell's arrangement of two adjacent square regions of 20 x 20 cells. The control zone consisted of well-connected, excitable cells, and the I-zone was made of weakly coupled cells (heptanol effect), which became spontaneously active as time evolved (isoproterenol effect). The dynamic events in the system have been studied numerically with the use of a finite difference method. Together, our experimental and computational data have revealed that the combination of low coupling, increased excitability, and spatial heterogeneity can lead to the development of ectopic waves confined to the injured network. This transient condition appears to serve as an essential step for the ectopic activity to "mature" before escaping into the surrounding control network.}, } @article {pmid12888489, year = {2003}, author = {Venkatesan, K and McManus, HR and Mello, CC and Smith, TF and Hansen, U}, title = {Functional conservation between members of an ancient duplicated transcription factor family, LSF/Grainyhead.}, journal = {Nucleic acids research}, volume = {31}, number = {15}, pages = {4304-4316}, pmid = {12888489}, issn = {1362-4962}, support = {R01 CA081157/CA/NCI NIH HHS/United States ; R01 CA081157-05/CA/NCI NIH HHS/United States ; CA81157/CA/NCI NIH HHS/United States ; }, mesh = {5' Flanking Region ; Amino Acid Sequence ; Animals ; Binding Sites ; Caenorhabditis elegans/anatomy & histology/embryology ; *Caenorhabditis elegans Proteins ; Conserved Sequence ; DNA-Binding Proteins/*genetics/metabolism ; Drosophila Proteins ; Drosophila melanogaster/genetics/growth & development ; *Evolution, Molecular ; Gene Duplication ; Genes, Lethal ; Membrane Glycoproteins ; Molecular Sequence Data ; *Phylogeny ; RNA Interference ; Sequence Alignment ; Transcription Factors/chemistry/*genetics/metabolism/physiology ; *Xenopus Proteins ; }, abstract = {The LSF/Grainyhead transcription factor family is involved in many important biological processes, including cell cycle, cell growth and development. In order to investigate the evolutionary conservation of these biological roles, we have characterized two new family members in Caenorhabditis elegans and Xenopus laevis. The C.elegans member, Ce-GRH-1, groups with the Grainyhead subfamily, while the X.laevis member, Xl-LSF, groups with the LSF subfamily. Ce-GRH-1 binds DNA in a sequence-specific manner identical to that of Drosophila melanogaster Grainyhead. In addition, Ce-GRH-1 binds to sequences upstream of the C.elegans gene encoding aromatic L-amino-acid decarboxylase and genes involved in post-embryonic development, mab-5 and dbl-1. All three C.elegans genes are homologs of D.melanogaster Grainyhead-regulated genes. RNA-mediated interference of Ce-grh-1 results in embryonic lethality in worms, accompanied by soft, defective cuticles. These phenotypes are strikingly similar to those observed previously in D.melanogaster grainyhead mutants, suggesting conservation of the developmental role of these family members over the course of evolution. Our phylogenetic analysis of the expanded LSF/GRH family (including other previously unrecognized proteins/ESTs) suggests that the structural and functional dichotomy of this family dates back more than 700 million years, i.e. to the time when the first multicellular organisms are thought to have arisen.}, } @article {pmid12887896, year = {2003}, author = {Kelleher, DJ and Karaoglu, D and Mandon, EC and Gilmore, R}, title = {Oligosaccharyltransferase isoforms that contain different catalytic STT3 subunits have distinct enzymatic properties.}, journal = {Molecular cell}, volume = {12}, number = {1}, pages = {101-111}, doi = {10.1016/s1097-2765(03)00243-0}, pmid = {12887896}, issn = {1097-2765}, support = {GM 43768/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Cell Membrane/*enzymology ; Eukaryotic Cells/*enzymology ; Evolution, Molecular ; Gene Expression Regulation, Enzymologic/genetics ; Glycoproteins/metabolism ; *Hexosyltransferases ; Humans ; Membrane Proteins/genetics/*isolation & purification ; Mice ; Molecular Sequence Data ; Phylogeny ; Polysaccharides/metabolism ; Protein Subunits/genetics/*isolation & purification ; *Saccharomyces cerevisiae Proteins ; Sequence Homology, Nucleic Acid ; Transferases/genetics/*isolation & purification ; }, abstract = {Oligosaccharyltransferase (OST) is an integral membrane protein that catalyzes N-linked glycosylation of nascent proteins in the lumen of the endoplasmic reticulum. Although the yeast OST is an octamer assembled from nonhomologous subunits (Ost1p, Ost2p, Ost3p/Ost6p, Ost4p, Ost5p, Wbp1p, Swp1p, and Stt3p), the composition of the vertebrate OST was less well defined. The roles of specific OST subunits remained enigmatic. Here we show that genomes of most multicellular eukaryotes encode two homologs of Stt3p and mammals express two homologs of Ost3p. The Stt3p and Ost3p homologs are assembled together with the previously described mammalian OST subunits (ribophorins I and II, OST48, and DAD1) into complexes that differ significantly in enzymatic activity. Tissue and cell type-specific differences in expression of the Stt3p homologs suggest that the enzymatic properties of oligosaccharyltransferase are regulated in eukaryotes to respond to alterations in glycoprotein flux through the secretory pathway and may contribute to tissue-specific glycan heterogeneity.}, } @article {pmid12885934, year = {2003}, author = {Streilein, JW}, title = {Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation.}, journal = {Journal of leukocyte biology}, volume = {74}, number = {2}, pages = {179-185}, doi = {10.1189/jlb.1102574}, pmid = {12885934}, issn = {0741-5400}, support = {EY 05678/EY/NEI NIH HHS/United States ; EY 10987/EY/NEI NIH HHS/United States ; }, mesh = {Antigen-Presenting Cells/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Eye/*immunology ; Humans ; Immunity, Cellular ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; Thrombospondins/immunology ; Transforming Growth Factor beta/immunology ; Uveitis, Anterior/*immunology ; }, abstract = {The delicate visual axis that makes precise vision possible is highly vulnerable to the destructive potential of immunogenic inflammation. Immune privilege of the eye is the experimental expression of the way in which evolution has coped with the countermanding threats to vision of ocular infections and ocular immunity and inflammation. Ocular immune privilege has five primary features that account for its existence: blood:ocular barriers, absent lymphatic drainage pathways, soluble immunomodulatory factors in aqueous humor, immunomodulatory ligands on the surface of ocular parenchymal cells, and indigenous, tolerance-promoting antigen-presenting cells (APCs). Three manifestations of ocular immune privilege that have received the most extensive study are the intraocular microenvironment, which is selectively anti-inflammatory and immunosuppressive; the prolonged acceptance of solid tissue and tumor allografts in the anterior chamber; and the induction of systemic tolerance to eye-derived antigens. Anterior chamber-associated immune deviation is known to arise when indigenous, ocular APCs capture eye-derived antigens and deliver them to the spleen where multicellular clusters of these cells, natural killer T cells, marginal zone B cells, and gammadelta T cells create an antigen-presentation environment that leads to CD4(+) and CD8(+) alpha/beta T cells, which as regulators, suppress induction and expression of T helper cell type 1 (Th1) and Th2 immune expression systems. The ways the eye influences local and systemic immune responses to ocular antigens and pathogens carry risks to and benefits for mammalian organisms. As loss of sight is a powerful, negative-selecting force, the benefits of ocular immune privilege outweigh the risks.}, } @article {pmid12885552, year = {2003}, author = {Tucker, ES and Tolbert, LP}, title = {Reciprocal interactions between olfactory receptor axons and olfactory nerve glia cultured from the developing moth Manduca sexta.}, journal = {Developmental biology}, volume = {260}, number = {1}, pages = {9-30}, doi = {10.1016/s0012-1606(03)00207-0}, pmid = {12885552}, issn = {0012-1606}, support = {DC04598/DC/NIDCD NIH HHS/United States ; }, mesh = {Actins/metabolism ; Animals ; Axons/metabolism ; Cells, Cultured ; Coculture Techniques ; Culture Media, Conditioned ; Growth Cones/metabolism ; Kinetics ; Manduca/cytology/*growth & development ; Microtubules/metabolism ; Models, Biological ; Neuroglia/cytology/*metabolism ; Olfactory Nerve/*cytology/growth & development ; Olfactory Receptor Neurons/cytology/growth & development/*metabolism ; }, abstract = {In olfactory systems, neuron-glia interactions have been implicated in the growth and guidance of olfactory receptor axons. In the moth Manduca sexta, developing olfactory receptor axons encounter several types of glia as they grow into the brain. Antennal nerve glia are born in the periphery and enwrap bundles of olfactory receptor axons in the antennal nerve. Although their peripheral origin and relationship with axon bundles suggest that they share features with mammalian olfactory ensheathing cells, the developmental roles of antennal nerve glia remain elusive. When cocultured with antennal nerve glial cells, olfactory receptor growth cones readily advance along glial processes without displaying prolonged changes in morphology. In turn, olfactory receptor axons induce antennal nerve glial cells to form multicellular arrays through proliferation and process extension. In contrast to antennal nerve glia, centrally derived glial cells from the axon sorting zone and antennal lobe never form arrays in vitro, and growth-cone glial-cell encounters with these cells halt axon elongation and cause permanent elaborations in growth cone morphology. We propose that antennal nerve glia play roles similar to olfactory ensheathing cells in supporting axon elongation, yet differ in their capacity to influence axon guidance, sorting, and targeting, roles that could be played by central olfactory glia in Manduca.}, } @article {pmid12871302, year = {2003}, author = {Freyssinet, JM}, title = {Cellular microparticles: what are they bad or good for?.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {1}, number = {7}, pages = {1655-1662}, doi = {10.1046/j.1538-7836.2003.00309.x}, pmid = {12871302}, issn = {1538-7933}, mesh = {Animals ; *Apoptosis ; Blood Platelets/*physiology ; Calcium/metabolism ; Cell Membrane/*metabolism ; Humans ; Models, Biological ; Phosphatidylserines/metabolism ; Phospholipids/*physiology ; Platelet Activation ; Platelet Membrane Glycoproteins/metabolism ; Thrombosis/*pathology ; }, abstract = {Microparticles are fragments released from the plasma membrane of most stimulated or apoptotic cells. After having long been considered inert cell debris, of possible value for the diagnosis of cell activation or death, there is increasing documented evidence that they can interact with neighboring or remote cells, in which case they acquire a pathophysiologic potential. On the one hand, deleterious microparticles stemming from activated cells can elicit an adverse response from other cells, themselves undergoing membrane vesiculation, leading to pathogenic amplification. On the other hand, since they are thought to reflect a balance between cell stimulation, proliferation, and death, it is conceivable that they are discerned as sensors for the maintenance of homeostasis in multicellular organisms. Because vesiculation is an integral part of the plasma-membrane remodeling process, with the transverse migration of procoagulant phosphatidylserine from the cytoplasmic to the exoplasmic leaflet as the central event, the majority of released microparticles are thought to fulfill a hemostatic function under physiologic conditions. This is particularly true when they originate from platelets, with possible deviation towards thrombosis when produced in excess. Owing to these procoagulant properties, the hemostasis laboratory offers the most appropriate tools for the assessment of the in vivo significance of microparticles.}, } @article {pmid12868611, year = {2003}, author = {Patthy, L}, title = {Modular assembly of genes and the evolution of new functions.}, journal = {Genetica}, volume = {118}, number = {2-3}, pages = {217-231}, pmid = {12868611}, issn = {0016-6707}, mesh = {*Evolution, Molecular ; Exons ; *Genes ; Genome ; Introns ; Proteins/genetics ; }, abstract = {Modular assembly of novel genes from existing genes has long been thought to be an important source of evolutionary novelty. Thanks to major advances in genomic studies it has now become clear that this mechanism contributed significantly to the evolution of novel biological functions in different evolutionary lineages. Analyses of completely sequenced bacterial, archaeal and eukaryotic genomes has revealed that modular assembly of novel constituents of various eukaryotic intracellular signalling pathways played a major role in the evolution of eukaryotes. Comparison of the genomes of single-celled eukaryotes, multicellular plants and animals has also shown that the evolution of multicellularity was accompanied by the assembly of numerous novel extracellular matrix proteins and extracellular signalling proteins that are absolutely essential for multicellularity. There is now strong evidence that exon-shuffling played a general role in the assembly of the modular proteins involved in extracellular communications of metazoa. Although some of these proteins seem to be shared by all major groups of metazoa, others are restricted to certain evolutionary lineages. The genomic features of the chordates appear to have favoured intronic recombination as evidenced by the fact that exon-shuffling continued to be a major source of evolutionary novelty during vertebrate evolution.}, } @article {pmid12840076, year = {2003}, author = {Bloomfield, G and Pears, C}, title = {Superoxide signalling required for multicellular development of Dictyostelium.}, journal = {Journal of cell science}, volume = {116}, number = {Pt 16}, pages = {3387-3397}, doi = {10.1242/jcs.00649}, pmid = {12840076}, issn = {0021-9533}, mesh = {Animals ; Cell Communication ; Dictyostelium/growth & development/*metabolism ; Mitochondria/drug effects/*metabolism ; Reactive Oxygen Species/metabolism ; Rotenone/pharmacology ; Signal Transduction ; Superoxide Dismutase/metabolism ; Superoxides/*metabolism ; Uncoupling Agents/pharmacology ; }, abstract = {Reactive oxygen species are known to have a signalling role in many organisms. In bacteria and yeast various response systems have evolved to combat oxidative stress which are triggered by reactive oxygen species. Mammals and plants are known to actively generate reactive oxygen species such as superoxide during signalling responses to a variety of extracellular factors. We report here the generation of superoxide as a signalling molecule in early development of Dictyostelium discoideum. Dictyostelium grows as single amoebae but, on starvation, the single cells aggregate to form a multicellular organism. Superoxide is generated in response to a secreted factor during the transition to the multicellular phase of development. Scavenging superoxide, either pharmacologically or by overexpressing the enzyme superoxide dismutase, inhibits the formation of the aggregate. This report of the use of superoxide as a signalling molecule in a lower eukaryote as it switches to a multicellular phase suggests that this signalling mechanism arose early in the evolution of multicellular organisms, perhaps as a necessary consequence of the need to diversify the number and type of signalling pathways available to facilitate intercellular communication.}, } @article {pmid12824488, year = {2003}, author = {Liu, J and Mushegian, A}, title = {Three monophyletic superfamilies account for the majority of the known glycosyltransferases.}, journal = {Protein science : a publication of the Protein Society}, volume = {12}, number = {7}, pages = {1418-1431}, pmid = {12824488}, issn = {0961-8368}, mesh = {Amino Acid Sequence ; Conserved Sequence/genetics ; Databases, Protein ; Evolution, Molecular ; Glycosyltransferases/chemistry/classification/*genetics ; Molecular Sequence Data ; *Multigene Family ; Nucleotidyltransferases/genetics ; Phylogeny ; Protein Folding ; Protein Structure, Secondary ; Sequence Alignment ; Statistics as Topic ; }, abstract = {Sixty-five families of glycosyltransferases (EC 2.4.x.y) have been recognized on the basis of high-sequence similarity to a founding member with experimentally demonstrated enzymatic activity. Although distant sequence relationships between some of these families have been reported, the natural history of glycosyltransferases is poorly understood. We used iterative searches of sequence databases, motif extraction, structural comparison, and analysis of completely sequenced genomes to track the origins of modern-type glycosyltransferases. We show that >75% of recognized glycosyltransferase families belong to one of only three monophyletic superfamilies of proteins, namely, (1) a recently described GPGTF/GT-B superfamily; (2) a nucleoside-diphosphosugar transferase (GT-A) superfamily, which is characterized by a DxD sequence signature and also includes nucleotidyltransferases; and (3) a GT-C superfamily of integral membrane glycosyltransferases with a modified DxD signature in the first extracellular loop. Several developmental regulators in Metazoans, including Fringe and Egghead homologs, belong to the second superfamily. Interestingly, Tout-velu/Exostosin family of developmental proteins found in all multicellular eukaryotes, contains separate domains belonging to the first and the second superfamilies, explaining multiple glycosyltransferase activities in one protein.}, } @article {pmid12819137, year = {2003}, author = {Semple, CA and , and , }, title = {The comparative proteomics of ubiquitination in mouse.}, journal = {Genome research}, volume = {13}, number = {6B}, pages = {1389-1394}, pmid = {12819137}, issn = {1088-9051}, mesh = {Animals ; Caenorhabditis elegans Proteins/chemistry/genetics/metabolism/physiology ; Databases, Genetic ; Drosophila Proteins/chemistry/genetics/metabolism/physiology ; Humans ; Mice ; Protein Structure, Tertiary/genetics ; Proteins/chemistry/genetics/metabolism/physiology ; Proteomics/*methods ; Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism/physiology ; Schizosaccharomyces pombe Proteins/chemistry/genetics/metabolism/physiology ; Ubiquitin/*genetics/*metabolism ; }, abstract = {Ubiquitination is a common posttranslational modification in eukaryotic cells, influencing many fundamental cellular processes. Defects in ubiquitination and the processes it mediates are involved in many human disease states. The ubiquitination of a substrate involves four classes of enzymes:a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), a ubiquitin protein ligase (E3), and a de-ubiquitinating enzyme (DUB). A substantial number of E1s (four), E2s (13), E3s (97), and DUBs (six) that were previously unknown in the mouse are included in the FANTOM2 Representative Transcript and Protein Set (RTPS). Many of the genes encoding these proteins will constitute promising candidates for involvement in disease. In addition, the RTPS provides the basis for the most comprehensive survey of ubiquitination-associated proteins across eukaryotes undertaken to date. Comparisons of these proteins across human and other organisms suggest that eukaryotic evolution has been associated with an increase in the number and diversity of E3s (possessing either zinc-finger RING, F-box, or HECT domains) and DUBs (containing the ubiquitin thiolesterase family 2 domain). These increases in numbers are too large to be accounted for by the presence of fragmentary proteins in the data sets examined. Much of this innovation appears to have been associated with the emergence of multicellular organisms, and subsequently of vertebrates, increasing the opportunity for complex regulation of ubiquitination-mediated cellular and developmental processes.}, } @article {pmid12815191, year = {2003}, author = {Ben-Shlomo, I and Yu Hsu, S and Rauch, R and Kowalski, HW and Hsueh, AJ}, title = {Signaling receptome: a genomic and evolutionary perspective of plasma membrane receptors involved in signal transduction.}, journal = {Science's STKE : signal transduction knowledge environment}, volume = {2003}, number = {187}, pages = {RE9}, doi = {10.1126/stke.2003.187.re9}, pmid = {12815191}, issn = {1525-8882}, mesh = {Animals ; Cell Membrane/*metabolism/physiology ; Databases, Protein ; *Evolution, Molecular ; *Genomics ; Humans ; Macromolecular Substances ; Receptors, Cell Surface/classification/*physiology ; Signal Transduction/*physiology ; }, abstract = {Intercellular communication in multicellular organisms requires the relay of extracellular signals by cell surface proteins to the interiors of cells. The availability of genome sequences from humans and several model organisms has facilitated the identification of several human plasma membrane receptor families and allowed the analysis of their phylogeny. This review provides a global categorization of most known signal transduction-associated receptors as enzymes, recruiters, and latent transcription factors. The evolution of known families of human plasma membrane signaling receptors was traced in current literature and validated by sequence relatedness. This global analysis reveals themes that recur during receptor evolution and allows the formulation of hypotheses for the origins of receptors. The human receptor families involved in signaling (with the exception of channels) are presented in the Human Plasma Membrane Receptome database.}, } @article {pmid12810693, year = {2003}, author = {Vajkoczy, P and Blum, S and Lamparter, M and Mailhammer, R and Erber, R and Engelhardt, B and Vestweber, D and Hatzopoulos, AK}, title = {Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis.}, journal = {The Journal of experimental medicine}, volume = {197}, number = {12}, pages = {1755-1765}, pmid = {12810693}, issn = {0022-1007}, mesh = {Animals ; Biomarkers ; Blood Vessels/cytology/metabolism ; Cell Adhesion/physiology ; Embryo, Mammalian ; Endothelium, Vascular/*cytology/embryology/metabolism ; Glioma/*blood supply/metabolism/pathology ; Hemodynamics ; Membrane Glycoproteins/metabolism ; Mice ; *Neovascularization, Pathologic ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Selectins/metabolism ; Stem Cells/*physiology ; }, abstract = {Tissue neovascularization involves recruitment of circulating endothelial progenitor cells that originate in the bone marrow. Here, we show that a class of embryonic endothelial progenitor cells (Tie-2+, c-Kit+, Sca-1+, and Flk-1-/low), which were isolated at E7.5 of mouse development at the onset of vasculogenesis, retain their ability to contribute to tumor angiogenesis in the adult. Using intravital fluorescence videomicroscopy, we further defined the multistep process of embryonic endothelial progenitor cell (eEPC) homing and incorporation. Circulating eEPCs are specifically arrested in "hot spots" within the tumor microvasculature, extravasate into the interstitium, form multicellular clusters, and incorporate into functional vascular networks. Expression analysis and in vivo blocking experiments provide evidence that the initial cell arrest of eEPC homing is mediated by E- and P-selectin and P-selectin glycoprotein ligand 1. This paper provides the first in vivo insights into the mechanisms of endothelial progenitor cell recruitment and, thus, indicates novel ways to interfere with pathological neovascularization.}, } @article {pmid12806785, year = {2003}, author = {Chaturvedi, R and Razdan, MK and Bhojwani, SS}, title = {An efficient protocol for the production of triploid plants from endosperm callus of neem, Azadirachta indica A. Juss.}, journal = {Journal of plant physiology}, volume = {160}, number = {5}, pages = {557-564}, doi = {10.1078/0176-1617-00884}, pmid = {12806785}, issn = {0176-1617}, mesh = {Azadirachta/cytology/*genetics/*growth & development ; Culture Techniques/*methods ; Plant Roots/cytology/genetics/growth & development ; Plant Shoots/cytology/genetics/growth & development ; *Polyploidy ; }, abstract = {Triploid plants of neem were obtained by immature endosperm culture. Immature seeds, at the early dicotyledonous stage of embryo development, is the best explant to raise endosperm callus on MS + NAA (5 mumol/L) + BAP (2 mumol/L) + CH (500 mg L-1). Maximum shoot bud differentiation from the endosperm callus occurred on MS + 5 mumol/L BAP. Shoots were multiplied by forced axillary branching and rooted in vitro. The plants were established in soil. Over 66% of the plants were triploid with chromosome number 2n = 3x = 36. A characteristic feature of the shoots of endosperm origin is the presence of a large number of multi-cellular glands.}, } @article {pmid12803893, year = {2003}, author = {Reeve, HK and Jeanne, RL}, title = {From individual control to majority rule: extending transactional models of reproductive skew in animal societies.}, journal = {Proceedings. Biological sciences}, volume = {270}, number = {1519}, pages = {1041-1045}, pmid = {12803893}, issn = {0962-8452}, mesh = {Animals ; Behavior, Animal/*physiology ; *Models, Biological ; *Reproduction ; *Social Behavior ; }, abstract = {Transactional concession models of social evolution explain the reproductive skew within groups by assuming that a dominant individual completely controls the allocation of reproduction to other group members. The models predict when the dominant will benefit from donating parcels of reproduction to other members in return for peaceful cooperation. Using linear programming methods, we present a 'majority-rules' model in which the summed actions of all society members, each with equal power, completely determine the reproductive share of any single member. The majority-rules model predicts that, despite the diffusion of power, a 'virtual dominant' (a dominant lacking special behavioural power) will emerge and that the reproductive skew will be exactly that predicted if the virtual dominant were to control completely the group's reproductive partitioning. The virtual dominant is the individual to which group members have the maximum average genetic relatedness. This result greatly broadens the applicability of transactional models of reproductive skew to social groups of any size, such as large-colony eusocial insects, and explains why queens in such colonies can achieve reproductive domination without any behavioural enforcement. Moreover, the majority-rules model unifies transactional-skew theory with models of worker policing and even generates a new theory for the cooperation among somatic cells in a multicellular organism.}, } @article {pmid12799498, year = {2003}, author = {Bonner, JT}, title = {On the origin of differentiation.}, journal = {Journal of biosciences}, volume = {28}, number = {4}, pages = {523-528}, pmid = {12799498}, issn = {0250-5991}, mesh = {Animals ; *Cell Differentiation ; Cell Physiological Phenomena ; Chlamydomonas/physiology ; Dictyosteliida/*genetics/*physiology ; Dictyostelium/physiology ; Morphogenesis ; }, abstract = {Following the origin of multicellularity in many groups of primitive organisms there evolved more than one cell type. It has been assumed that this early differentiation is related to size the larger the organism the more cell types. Here two very different kinds of organisms are considered: the volvocine algae that become multicellular by growth, and the cellular slime moulds that become multicellular by aggregation. In both cases there are species that have only one cell type and others that have two. It has been possible to show that there is a perfect correlation with size: the forms with two cell types are significantly larger than those with one. Also in both groups there are forms of intermediate size that will vary from one to two cell types depending on the size of the individuals, suggesting a form of quorum sensing. These observations reinforce the view that size plays a critical role in influencing the degree of differentiation.}, } @article {pmid12794193, year = {2003}, author = {Grohmann, E and Muth, G and Espinosa, M}, title = {Conjugative plasmid transfer in gram-positive bacteria.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {67}, number = {2}, pages = {277-301, table of contents}, pmid = {12794193}, issn = {1092-2172}, mesh = {Amino Acid Sequence ; Base Sequence ; Conjugation, Genetic/*genetics ; DNA, Bacterial/genetics ; Gram-Negative Bacteria/genetics ; Gram-Positive Bacteria/*genetics ; Molecular Sequence Data ; Plasmids/*genetics ; R Factors/genetics ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; }, abstract = {Conjugative transfer of bacterial plasmids is the most efficient way of horizontal gene spread, and it is therefore considered one of the major reasons for the increase in the number of bacteria exhibiting multiple-antibiotic resistance. Thus, conjugation and spread of antibiotic resistance represents a severe problem in antibiotic treatment, especially of immunosuppressed patients and in intensive care units. While conjugation in gram-negative bacteria has been studied in great detail over the last decades, the transfer mechanisms of antibiotic resistance plasmids in gram-positive bacteria remained obscure. In the last few years, the entire nucleotide sequences of several large conjugative plasmids from gram-positive bacteria have been determined. Sequence analyses and data bank comparisons of their putative transfer (tra) regions have revealed significant similarities to tra regions of plasmids from gram-negative bacteria with regard to the respective DNA relaxases and their targets, the origins of transfer (oriT), and putative nucleoside triphosphatases NTP-ases with homologies to type IV secretion systems. In contrast, a single gene encoding a septal DNA translocator protein is involved in plasmid transfer between micelle-forming streptomycetes. Based on these clues, we propose the existence of two fundamentally different plasmid-mediated conjugative mechanisms in gram-positive microorganisms, namely, the mechanism taking place in unicellular gram-positive bacteria, which is functionally similar to that in gram-negative bacteria, and a second type that occurs in multicellular gram-positive bacteria, which seems to be characterized by double-stranded DNA transfer.}, } @article {pmid12787815, year = {2003}, author = {Huettenbrenner, S and Maier, S and Leisser, C and Polgar, D and Strasser, S and Grusch, M and Krupitza, G}, title = {The evolution of cell death programs as prerequisites of multicellularity.}, journal = {Mutation research}, volume = {543}, number = {3}, pages = {235-249}, doi = {10.1016/s1383-5742(02)00110-2}, pmid = {12787815}, issn = {0027-5107}, mesh = {Animals ; Apoptosis ; *Biological Evolution ; Humans ; Mitochondria/physiology ; Necrosis ; }, abstract = {One of the hallmarks of multicellularity is that the individual cellular fate is sacrificed for the benefit of a higher order of life-the organism. The accidental death of cells in a multicellular organism results in swelling and membrane-rupture and inevitably spills cell contents into the surrounding tissue with deleterious effects for the organism. To avoid this form of necrotic death the cells of metazoans have developed complex self-destruction mechanisms, collectively called programmed cell death, which see to an orderly removal of superfluous cells. Since evolution never invents new genes but plays variations on old themes by DNA mutations, it is not surprising, that some of the genes involved in metazoan death pathways apparently have evolved from homologues in unicellular organisms, where they originally had different functions. Interestingly some unicellular protozoans have developed a primitive form of non-necrotic cell death themselves, which could mean that the idea of an altruistic death for the benefit of genetically identical cells predated the invention of multicellularity. The cell death pathways of protozoans, however, show no homology to those in metazoans, where several death pathways seem to have evolved in parallel. Mitochondria stands at the beginning of several death pathways and also determines, whether a cell has sufficient energy to complete a death program. However, the endosymbiotic bacterial ancestors of mitochondria are unlikely to have contributed to the recent mitochondrial death machinery and therefore, these components may derive from mutated eukaryotic precursors and might have invaded the respective mitochondrial compartments. Although there is no direct evidence, it seems that the prokaryotic-eukaryotic symbiosis created the space necessary for sophisticated death mechanisms on command, which in their distinct forms are major factors for the evolution of multicellular organisms.}, } @article {pmid12765787, year = {2003}, author = {Popescu, O and Checiu, I and Gherghel, P and Simon, Z and Misevic, GN}, title = {Quantitative and qualitative approach of glycan-glycan interactions in marine sponges.}, journal = {Biochimie}, volume = {85}, number = {1-2}, pages = {181-188}, doi = {10.1016/s0300-9084(03)00063-4}, pmid = {12765787}, issn = {0300-9084}, mesh = {Animals ; Calcium ; Cations, Divalent ; Cell Adhesion Molecules/*chemistry/metabolism ; Immunoglobulin Fab Fragments/chemistry/metabolism ; Magnesium ; Microscopy, Atomic Force ; Polysaccharides/*chemistry/metabolism ; Porifera/chemistry/*physiology ; Proteoglycans/*chemistry/metabolism ; }, abstract = {Cell recognition and adhesion involving many kinds of cell surface molecules operate via homotypic and/or heterotypic protein-protein and protein-carbohydrate binding. Our investigations in marine sponges have provided direct evidence for a novel molecular mechanism of multivalent glycan-glycan binding related to cellular interactions. Biochemical characterization of purified proteoglycans revealed the presence of specific acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight, containing fucose, glucuronic or galacturonic acids, and pyruvate and sulfate groups may represent a new class of primordial proteoglycans, named by us glyconectins. The thermodynamic and kinetic approaches of biological macromolecule interactions do not provide a direct measurement of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Using the atomic force microscopy (AFM), we provided the first quantitative evaluation of the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion glyconectin proteoglycans (AGPs) is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. (i) As a model, we selected the cell AGP isolated from the marine sponge Microciona prolifera; it mediates in vivo cell recognition and aggregation via homotypic, species-specific, multivalent, and calcium ion-dependent glycan-glycan interactions. (ii) Under physiological conditions, a large cohesive force theoretically able to hold the weight of approximately 1600 cells was measured. (iii) The C-2 autocomplementarity model for AGP-AGP interactions; and (iv) the requirement of the calcium ionic bridges suggest also that the self-recognition and multivalency of glycan-glycan interactions are essential for cell adhesion. (v) The evolution of glyconectin-like proteoglycan molecules may have been a fundamental prerequisite for the emergence of the first multicellular organisms. Glycan-glycan interactions may thus provide a new paradigm for molecular self-recognition.}, } @article {pmid12761193, year = {2003}, author = {Suzuki, A and Akimoto, K and Ohno, S}, title = {Protein kinase C lambda/iota (PKClambda/iota): a PKC isotype essential for the development of multicellular organisms.}, journal = {Journal of biochemistry}, volume = {133}, number = {1}, pages = {9-16}, doi = {10.1093/jb/mvg018}, pmid = {12761193}, issn = {0021-924X}, mesh = {Animals ; Biological Evolution ; Cell Polarity ; Epithelium/enzymology ; Humans ; Isoenzymes/chemistry/metabolism/*physiology ; Mice ; Protein Kinase C/chemistry/metabolism/*physiology ; Protein Structure, Tertiary ; Signal Transduction ; }, abstract = {PKClambda/iota belongs to the third group of the PKC family, atypical PKC (aPKC), together with PKCzeta based on its sequence divergence from conventional and novel PKCs observed not only in the N-terminal regulatory domain but also in the kinase domain. Although one of the most distinct features of aPKC is its single, unrepeated cysteine-rich domain, recent studies have revealed that the N-terminal regulatory domain has additional aPKC-specific structural motifs involved in various protein-protein interactions, which are important for the regulation and the subcellular targeting of aPKC. The identification of aPKC-specific binding proteins has significantly facilitated our understanding of the activation mechanism as well as the physiological function of aPKC at the molecular level. In particular, the finding that the mammalian homologs of the Caenorhabditis elegans proteins, PAR-3 and PAR-6, bind aPKC unexpectedly opens a new avenue for exploring a thus far completely unrecognized critical function of aPKC, that is, as a component of an evolutionarily conserved cell polarity machinery. Together with the great progress in the genome project as well as in the genetic analysis of model organisms, these advances are leading us into the new era of aPKC study in which functional divergence between PKClambda/iota and zeta can be discussed in elaborately.}, } @article {pmid12752763, year = {2003}, author = {Perović, S and Schröder, HC and Sudek, S and Grebenjuk, VA and Batel, R and Stifanić, M and Müller, IM and Müller, WE}, title = {Expression of one sponge Iroquois homeobox gene in primmorphs from Suberites domuncula during canal formation.}, journal = {Evolution & development}, volume = {5}, number = {3}, pages = {240-250}, doi = {10.1046/j.1525-142x.2003.03023.x}, pmid = {12752763}, issn = {1520-541X}, mesh = {Animals ; Base Sequence ; Blotting, Northern ; Cluster Analysis ; DNA Primers ; Ferric Compounds/metabolism ; *Gene Expression Profiling ; Genes, Homeobox/*genetics ; In Situ Hybridization ; Molecular Sequence Data ; *Phylogeny ; Porifera/*anatomy & histology/*genetics ; Sequence Analysis, DNA ; }, abstract = {Sponges (Porifera) represent the evolutionary oldest multicellular animals. They are provided with the basic molecules involved in cell-cell and cell-matrix interactions. We report here the isolation and characterization of a complementary DNA from the sponge Suberites domuncula coding for the sponge homeobox gene, SUBDOIRX-a. The deduced polypeptide with a predicted Mr of 44,375 possesses the highly conserved Iroquois-homeodomain. We applied in situ hybridization to localize Iroquois in the sponge. The expression of this gene is highest in cells adjacent to the canals of the sponge in the medulla region. To study the expression of Iroquois during development, the in vitro primmorph system from S. domuncula was used. During the formation of these three-dimensional aggregates composed of proliferating cells, the expression of Iroquois depends on ferric iron and water current. An increased expression in response to water current is paralleled with the formation of canal-like pores in the primmorphs. It is suggested that Iroquois expression is involved in the formation of the aquiferous system, the canals in sponges and the canal-like structures in primmorphs.}, } @article {pmid12750476, year = {2003}, author = {Tarrio, R and Rodríguez-Trelles, F and Ayala, FJ}, title = {A new Drosophila spliceosomal intron position is common in plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {100}, number = {11}, pages = {6580-6583}, pmid = {12750476}, issn = {0027-8424}, support = {GM42397/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Drosophila/*genetics ; *Introns ; Plants/*genetics ; *Spliceosomes ; }, abstract = {The 25-year-old debate about the origin of introns between proponents of "introns early" and "introns late" has yielded significant advances, yet important questions remain to be ascertained. One question concerns the density of introns in the last common ancestor of the three multicellular kingdoms. Approaches to this issue thus far have relied on counts of the numbers of identical intron positions across present-day taxa on the assumption that the introns at those sites are orthologous. However, dismissing parallel intron gain for those sites may be unwarranted, because various factors can potentially constrain the site of intron insertion. Demonstrating parallel intron gain is severely handicapped, because intron sequences often evolve exceedingly fast and intron phylogenetic distributions are usually ambiguous, such that alternative loss and gain scenarios cannot be clearly distinguished. We have identified an intron position that was gained independently in animals and plants in the xanthine dehydrogenase gene. The extremely disjointed phylogenetic distribution of the intron argues strongly for separate gain rather than recurrent loss. If the observed phylogenetic pattern had resulted from recurrent loss, all observational support previously gathered for the introns-late theory of intron origins based on the phylogenetic distribution of introns would be invalidated.}, } @article {pmid12746516, year = {2003}, author = {Segovia, M and Haramaty, L and Berges, JA and Falkowski, PG}, title = {Cell death in the unicellular chlorophyte Dunaliella tertiolecta. A hypothesis on the evolution of apoptosis in higher plants and metazoans.}, journal = {Plant physiology}, volume = {132}, number = {1}, pages = {99-105}, pmid = {12746516}, issn = {0032-0889}, mesh = {Algal Proteins/metabolism ; Apoptosis/*genetics/physiology ; Blotting, Western ; Caspases/metabolism ; Cell Division/genetics/radiation effects ; Cell Nucleus/metabolism ; Chlorophyta/*genetics/growth & development/ultrastructure ; Chromatin/metabolism ; DNA Fragmentation ; Darkness ; *Evolution, Molecular ; In Situ Nick-End Labeling ; Microscopy, Electron ; Plants/*genetics ; }, abstract = {Apoptosis is essential for normal growth and development of multicellular organisms, including metazoans and higher plants. Although cell death processes have been reported in unicellular organisms, key elements of apoptotic pathways have not been identified. Here, we show that when placed in darkness, the unicellular chlorophyte alga Dunaliella tertiolecta undergoes a form of cell death reminiscent of apoptosis in metazoans. Many morphological criteria of apoptotic cell death were met, including an increase in chromatin margination, degradation of the nucleus, and DNA fragmentation. Biochemical assays of the activities of cell death-associated proteases, caspases, measured using highly specific fluorogenic substrates, increased with time in darkness and paralleled the morphological changes. The caspase-like activities were inhibited by caspase-specific inhibitors. Antibodies raised against mammalian caspases cross-reacted with specific proteins in the alga. The pattern of expression of these immunologically reactive proteins was correlated with the onset of cell death. The occurrence of key components of apoptosis, and particularly a caspase-mediated cell death cascade in a relatively ancient linage of eukaryotic photoautotrophs, argues against current theories that cell death evolved in multicellular organisms. We hypothesize that key elements of cell death pathways were transferred to the nuclear genome of early eukaryotes through ancient viral infections in the Precambrian Ocean before the evolution of multicellular organisms and were subsequently appropriated in both metazoan and higher plant lineages.}, } @article {pmid12743821, year = {2003}, author = {Kawashima, T and Tokuoka, M and Awazu, S and Satoh, N and Satou, Y}, title = {A genomewide survey of developmentally relevant genes in Ciona intestinalis. VIII. Genes for PI3K signaling and cell cycle.}, journal = {Development genes and evolution}, volume = {213}, number = {5-6}, pages = {284-290}, pmid = {12743821}, issn = {0949-944X}, mesh = {Animals ; Cell Cycle/*genetics ; Ciona intestinalis/embryology/*genetics ; Cluster Analysis ; Databases, Genetic ; *Genome ; Phosphatidylinositol 3-Kinases/*genetics ; *Phylogeny ; Signal Transduction/*genetics ; }, abstract = {Cell growth and cell divisions are two fundamental biological processes for cells in multi-cellular organisms. The molecules involved in these biological processes are highly conserved within eukaryotes, including plants and unicellular organisms such as yeast. However, some regulatory molecules seem to be innovated during animal evolution. Therefore, to understand how the ubiquitous systems have evolved or have been conserved, we examined genes for the phosphoinositide 3-kinase (PI3K) pathway that is important for cell growth, and genes for cell cycle regulation in the genome of Ciona intestinalis. It was found that the Ciona intestinalis genome contains all the essential constituents of the PI3K pathway. In addition, the class IB PI3K catalytic and regulatory subunits, which had not previously been known in animals other than mammals, were found in the Ciona genome. Similarly, all essential cyclins and CDKs were found in the Ciona genome, while cyclin G and cyclin L were likely to be independently lost in the ascidian lineage, which may be dispensable for the cell cycle. Cyclin F, which was previously known only in vertebrates, was not found in the Ciona genome. Therefore, this gene was probably innovated during the evolution of vertebrates to be involved in vertebrate-specific cell cycle regulation. Since Ciona is regarded as one of the most primitive extant chordates, the present analysis gives us an insight into how these fundamental biological genes are evolved or are conserved during chordate evolution.}, } @article {pmid12736201, year = {2003}, author = {Hennig, L and Taranto, P and Walser, M and Schönrock, N and Gruissem, W}, title = {Arabidopsis MSI1 is required for epigenetic maintenance of reproductive development.}, journal = {Development (Cambridge, England)}, volume = {130}, number = {12}, pages = {2555-2565}, doi = {10.1242/dev.00470}, pmid = {12736201}, issn = {0950-1991}, mesh = {Arabidopsis/*embryology/genetics ; Arabidopsis Proteins/genetics/*metabolism ; Computational Biology ; Flowering Tops/growth & development ; Gene Expression Regulation, Plant/physiology ; Heterochromatin/physiology ; Phylogeny ; Plant Leaves/growth & development ; RNA Interference/physiology ; RNA, Messenger/metabolism ; }, abstract = {WD40 repeat proteins similar to yeast MSI1 are conserved in animals and plants, in which they participate in complexes involved in chromatin metabolism. Although MSI1-like proteins are well characterised biochemically, their function in the development of multicellular eukaryotes is not well understood. We constructed Arabidopsis plants in which the AtMSI1 protein level was altered. Strong ectopic expression of AtMSI1 produced no visible altered phenotype, but reduction of AtMSI1 dramatically affected development. The primary shoot apical meristem was unable to develop organs after the transition to flowering. Flowers that developed on floral shoots from axillary meristems experienced a progressive loss of floral morphology, including a reduction in size of the petals and stamens and the development of carpel-like sepals. Ovule development was disrupted in all flowers, resulting in complete female sterility. Molecular analysis of the mutant plants revealed that AtMSI1 is required to maintain the correct temporal and organ-specific expression of homeotic genes, including AGAMOUS and APETALA2. In contrast, FAS1 and FAS2, which together with AtMSI1 form the chromatin assembly complex CAF-1, are not required for repression of these genes. Therefore, AtMSI1 has specific functions in addition to CAF-1-mediated chromatin assembly. Efficient formation of heterochromatin, but not methylation of centromeric DNA repeats, depends on AtMSI1 presence demonstrating a key role of AtMSI1 in maintenance of chromatin structure.}, } @article {pmid12731056, year = {2003}, author = {Silzle, T and Kreutz, M and Dobler, MA and Brockhoff, G and Knuechel, R and Kunz-Schughart, LA}, title = {Tumor-associated fibroblasts recruit blood monocytes into tumor tissue.}, journal = {European journal of immunology}, volume = {33}, number = {5}, pages = {1311-1320}, doi = {10.1002/eji.200323057}, pmid = {12731056}, issn = {0014-2980}, mesh = {Breast Neoplasms/*pathology ; *Cell Communication ; Cell Movement ; Chemokines, CC/physiology ; Coculture Techniques ; Cytokines/biosynthesis ; Female ; Fibroblasts/*physiology ; Humans ; Interleukin-6/physiology ; Monocytes/*physiology ; Spheroids, Cellular ; }, abstract = {Tumor-associated fibroblasts (TAF) and tumor-associated macrophages are the main stromal components in desmoplastic breast tumors. These host cell types were extensively studied individually with regard to tumor development and progression but little is known about their reciprocal interactions. To elucidate the role of TAF in the recruitment of monocytes (MO) we designed a 3D co-culture system of multicellular fibroblast spheroids of different origin, co-cultured with MO suspensions from healthy donors. Spheroids of tumor-derived but not of normal fibroblasts were extensively infiltrated by MO. A linear correlation between number of infiltrated MO and number of MO applied per spheroid was shown, indicating a distinct migratory MO subpopulation (approximately 15%) within the peripheral blood MO pool. Our data imply that MO migration into fibroblastic tumor areas may partially result from high expression of CCL2 (monocyte chemotactic protein-1), which was regulated by endogenous IL-6 as shown by neutralization experiments. The effect of CCL2 on MO migration was inhibited by CCL2 neutralizing antibody in tumor-derived fibroblast conditioned media in a Boyden chamber migration assay but not in spheroid culture. While this phenomenon needs further evaluation, our data clearly support the concept of fibroblasts as "sentinel cells" relevant for tumor progression.}, } @article {pmid12729588, year = {2003}, author = {Clavería, C and Torres, M}, title = {Mitochondrial apoptotic pathways induced by Drosophila programmed cell death regulators.}, journal = {Biochemical and biophysical research communications}, volume = {304}, number = {3}, pages = {531-537}, doi = {10.1016/s0006-291x(03)00626-0}, pmid = {12729588}, issn = {0006-291X}, mesh = {Amino Acid Sequence ; Animals ; *Apoptosis ; Biological Evolution ; Drosophila Proteins/chemistry/*metabolism ; Drosophila melanogaster/cytology/*metabolism ; Mitochondria/*metabolism ; Models, Biological ; Protein Structure, Tertiary ; Signal Transduction ; }, abstract = {Multicellular organisms eliminate unwanted or damaged cells by cell death, a process essential to the maintenance of tissue homeostasis. Cell death is a tightly regulated event, whose alteration by excess or defect is involved in the pathogenesis of many diseases such as cancer, autoimmune syndromes, and neurodegenerative processes. Studies in model organisms, especially in the nematode Caenorhabditis elegans, have been crucial in identifying the key molecules implicated in the regulation and execution of programmed cell death. In contrast, the study of cell death in Drosophila melanogaster, often an excellent model organism, has identified regulators and mechanisms not obviously conserved in other metazoans. Recent molecular and cellular analyses suggest, however, that the mechanisms of action of the main programmed cell death regulators in Drosophila include a canonical mitochondrial pathway.}, } @article {pmid12729583, year = {2003}, author = {van Gurp, M and Festjens, N and van Loo, G and Saelens, X and Vandenabeele, P}, title = {Mitochondrial intermembrane proteins in cell death.}, journal = {Biochemical and biophysical research communications}, volume = {304}, number = {3}, pages = {487-497}, doi = {10.1016/s0006-291x(03)00621-1}, pmid = {12729583}, issn = {0006-291X}, mesh = {Animals ; *Apoptosis ; Apoptosis Inducing Factor ; Apoptosis Regulatory Proteins ; Carrier Proteins/physiology ; Cytochrome c Group/physiology ; Endodeoxyribonucleases/physiology ; Flavoproteins/physiology ; High-Temperature Requirement A Serine Peptidase 2 ; Intracellular Membranes/metabolism ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins/*physiology ; Mitochondria/metabolism ; Mitochondrial Proteins/*physiology ; Models, Biological ; Oxidative Phosphorylation ; Serine Endopeptidases/physiology ; }, abstract = {Apoptosis is a form of programmed cell death important in the development and tissue homeostasis of multicellular organisms. Mitochondria have, next to their function in respiration, an important role in the apoptotic-signaling pathway. Malfunctioning at any level of the cell is eventually translated in the release of apoptogenic factors from the mitochondrial intermembrane space resulting in the organized demise of the cell. Some of these factors, such as AIF and endonuclease G, appear to be highly conserved during evolution. Other factors, like cytochrome c, have gained their apoptogenic function later during evolution. In this review, we focus on the role of cytochrome c, AIF, endonuclease G, Smac/DIABLO, Omi/HtrA2, Acyl-CoA-binding protein, and polypyrimidine tract-binding protein in the initiation and modulation of cell death in different model organisms. These mitochondrial factors may contribute to both caspase-dependent and caspase-independent processes in apoptotic cell death.}, } @article {pmid12728279, year = {2003}, author = {Walbot, V and Evans, MM}, title = {Unique features of the plant life cycle and their consequences.}, journal = {Nature reviews. Genetics}, volume = {4}, number = {5}, pages = {369-379}, doi = {10.1038/nrg1064}, pmid = {12728279}, issn = {1471-0056}, mesh = {Animals ; Genes, Plant/physiology ; Life Cycle Stages/*physiology ; *Plant Development ; }, abstract = {Continuous development, the absence of a germline, flexible and reversible cellular differentiation, and the existence of haploid and diploid generations--both of which express genes--are characteristics that distinguish plants from animals. Because these differences alter the impact of mutations, animals and plants experience varied selection pressures. Despite different life-cycles, both flowering plants and multicellular animals have evolved complex sensing mechanisms that act after fertilization as 'quality checks' on reproduction, and that detect chromosome dosage and the parent of origin for specific genes. Although flowering plant embryos escape such surveillance in vitro, embryo success in the seed often depends on a healthy endosperm--a nutritive tissue that is produced by a second fertilization event in which maternal and paternal gene contributions can be monitored immediately after fertilization and throughout development.}, } @article {pmid12724425, year = {2003}, author = {Jedrusik, MA and Schulze, E}, title = {Telomeric position effect variegation in Saccharomyces cerevisiae by Caenorhabditis elegans linker histones suggests a mechanistic connection between germ line and telomeric silencing.}, journal = {Molecular and cellular biology}, volume = {23}, number = {10}, pages = {3681-3691}, pmid = {12724425}, issn = {0270-7306}, mesh = {Animals ; Caenorhabditis elegans/*metabolism ; Cell Nucleus/metabolism ; Chromatin/metabolism ; DNA/metabolism ; Flow Cytometry ; Fluorescent Antibody Technique, Indirect ; *Gene Silencing ; Green Fluorescent Proteins ; Histones/metabolism ; Hydroxamic Acids/pharmacology ; Luminescent Proteins/metabolism ; Peptides/chemistry ; Phylogeny ; Precipitin Tests ; Protein Structure, Tertiary ; Protein Synthesis Inhibitors/pharmacology ; Protein Transport ; RNA Interference ; Saccharomyces cerevisiae/*metabolism ; Software ; *Telomere ; }, abstract = {Linker histones are nonessential for the life of single-celled eukaryotes. Linker histones, however, can be important components of specific developmental programs in multicellular animals and plants. For Caenorhabditis elegans a single linker histone variant (H1.1) is essential in a chromatin silencing process which is crucial for the proliferation and differentiation of the hermaphrodite germ line. In this study we analyzed the whole linker histone complement of C. elegans by telomeric position effect variegation in budding yeast. In this assay an indicator gene (URA3) placed close to the repressive telomeric chromatin structure is subject to epigenetically inherited gene inactivation. Just one out of seven C. elegans linker histones (H1.1) was able to enhance the telomeric position effect in budding yeast. Since these results reflect the biological function of H1.1 in C. elegans, we suggest that chromatin silencing in C. elegans is governed by molecular mechanisms related to the telomere-dependent silencing in budding yeast. We confirmed this hypothesis by testing C. elegans homologs of three yeast genes which are established modifiers of the yeast telomeric chromatin structure (SIR2, SET1, and RAD17) for their influence on repeat-dependent transgene silencing for C. elegans.}, } @article {pmid12718397, year = {2003}, author = {Furusawa, G and Yoshikawa, T and Yasuda, A and Sakata, T}, title = {Algicidal activity and gliding motility of Saprospira sp. SS98-5.}, journal = {Canadian journal of microbiology}, volume = {49}, number = {2}, pages = {92-100}, doi = {10.1139/w03-017}, pmid = {12718397}, issn = {0008-4166}, mesh = {Base Sequence ; Culture Media ; Diatoms/*cytology/drug effects/ultrastructure ; Gram-Negative Anaerobic Straight, Curved, and Helical Rods/cytology/*physiology/ultrastructure ; Microtubules/ultrastructure ; Movement ; Peptones/pharmacology ; Phylogeny ; RNA, Ribosomal, 16S/analysis ; Sequence Alignment ; }, abstract = {A marine bacterium, Saprospira sp. SS98-5, which was isolated from Kagoshima Bay, Japan, was able to kill and lyse the cells of the diatom Chaetoceros ceratosporum. The multicellular filamentous cells of this bacterium captured the diatom cells, formed cell aggregates, and lysed them in an enriched sea water (ESS) liquid medium. Strain SS98-5 also formed plaques on double layer agar plates incorporating diatom cells. The diatom cell walls were partially degraded at the contact sites with the bacteria, the bacteria invaded from there into the diatom cells, and then the diatom cells were completely lysed. The strain possessed gliding motility and grew as spreading colonies on ESS agar plates containing lower concentrations of polypeptone (below 0.1%) while forming nonspreading colonies on ESS agar plates containing 0.5% polypeptone. Electron micrographs of ultrathin sections demonstrated that microtubule-like structures were observable only in gliding motile cells. Both the gliding motility and the microtubule-like structures were diminished by the addition of podophyllotoxin, an inhibitor of microtubule assembly, suggesting that the microtubule-like structures observed in these bacterial cells are related to their gliding motility.}, } @article {pmid12705473, year = {2003}, author = {Kloc, M and Biliński, SM}, title = {RNA localization and its role in the spatially restricted protein synthesis.}, journal = {Folia histochemica et cytobiologica}, volume = {41}, number = {1}, pages = {3-11}, pmid = {12705473}, issn = {0239-8508}, support = {GM50221/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Polarity ; Evolution, Molecular ; Humans ; Models, Biological ; Molecular Motor Proteins/metabolism ; Protein Biosynthesis ; Protein Sorting Signals ; RNA/*analysis/physiology ; RNA Transport ; RNA, Messenger/genetics/metabolism ; }, abstract = {RNA localization is an evolutionarily conserved phenomenon that occurs in uni- and multi-cellular animal and plant species. Localized RNA plays a role in the establishment of cell polarity and/or the determination of cell fate. In recent years, it became evident that the major function of RNA localization is the creation of a high concentration of proteins in specific cellular compartments. The movement of RNA involves interactions between targeting signals within the RNA molecule, cytoskeleton, and molecular motors. Translocating RNA must be translationally silent, and on-site translation at the destination site requires a de-repression mechanism. This is probably achieved by sequestering RNA and the regulators of translation within the multiprotein RNP complexes that co-translocate all the components to the ultimate destination within the cell.}, } @article {pmid12689728, year = {2003}, author = {Poole, AM and Phillips, MJ and Penny, D}, title = {Prokaryote and eukaryote evolvability.}, journal = {Bio Systems}, volume = {69}, number = {2-3}, pages = {163-185}, doi = {10.1016/s0303-2647(02)00131-4}, pmid = {12689728}, issn = {0303-2647}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Biological Evolution ; Ecosystem ; *Eukaryotic Cells ; Gene Expression Regulation/genetics ; Genetic Variation ; *Genome ; Humans ; *Models, Genetic ; Mutation/genetics ; *Prokaryotic Cells ; Selection, Genetic ; Species Specificity ; Stress, Physiological/*genetics ; }, abstract = {The concept of evolvability covers a broad spectrum of, often contradictory, ideas. At one end of the spectrum it is equivalent to the statement that evolution is possible, at the other end are untestable post hoc explanations, such as the suggestion that current evolutionary theory cannot explain the evolution of evolvability. We examine similarities and differences in eukaryote and prokaryote evolvability, and look for explanations that are compatible with a wide range of observations. Differences in genome organisation between eukaryotes and prokaryotes meets this criterion. The single origin of replication in prokaryote chromosomes (versus multiple origins in eukaryotes) accounts for many differences because the time to replicate a prokaryote genome limits its size (and the accumulation of junk DNA). Both prokaryotes and eukaryotes appear to switch from genetic stability to genetic change in response to stress. We examine a range of stress responses, and discuss how these impact on evolvability, particularly in unicellular organisms versus complex multicellular ones. Evolvability is also limited by environmental interactions (including competition) and we describe a model that places limits on potential evolvability. Examples are given of its application to predator competition and limits to lateral gene transfer. We suggest that unicellular organisms evolve largely through a process of metabolic change, resulting in biochemical diversity. Multicellular organisms evolve largely through morphological changes, not through extensive changes to cellular biochemistry.}, } @article {pmid12689724, year = {2003}, author = {Michod, RE and Nedelcu, AM and Roze, D}, title = {Cooperation and conflict in the evolution of individuality. IV. Conflict mediation and evolvability in Volvox carteri.}, journal = {Bio Systems}, volume = {69}, number = {2-3}, pages = {95-114}, doi = {10.1016/s0303-2647(02)00133-8}, pmid = {12689724}, issn = {0303-2647}, mesh = {Adaptation, Physiological/genetics ; Animals ; *Biological Evolution ; Caenorhabditis elegans/genetics/growth & development ; Chlorophyta/classification/*genetics/growth & development ; Computer Simulation ; *Conflict, Psychological ; *Cooperative Behavior ; Gene Expression Regulation/genetics ; Genetic Variation ; Germ Cells/growth & development ; Germ-Line Mutation/genetics ; Individuality ; *Models, Genetic ; Phenotype ; *Population Dynamics ; Selection, Genetic ; Species Specificity ; }, abstract = {The continued well being of evolutionary individuals (units of selection and evolution) depends upon their evolvability, that is their capacity to generate and evolve adaptations at their level of organization, as well as their longer term capacity for diversifying into more complex evolutionary forms. During a transition from a lower- to higher-level individual, such as the transition between unicellular and multicellular organisms, the evolvability of the lower-level (cells) must be restricted, while the evolvability of the new higher-level unit (multicellular organism) must be enhanced. For these reasons, understanding the factors leading to an evolutionary transition should help us to understand the factors underlying the emergence of evolvability of a new evolutionary unit. Cooperation among lower-level units is fundamental to the origin of new functions in the higher-level unit. Cooperation can produce a new more complex evolutionary unit, with the requisite properties of heritable fitness variations, because cooperation trades fitness from a lower-level (the costs of cooperation) to the higher-level (the benefits for the group). For this reason, the evolution of cooperative interactions helps us to understand the origin of new and higher-levels of fitness and organization. As cooperation creates a new level of fitness, it also creates the opportunity for conflict between levels of selection, as deleterious mutants with differing effects at the two levels arise and spread. This conflict can interfere with the evolvability of the higher-level unit, since the lower and higher-levels of selection will often "disagree" on what adaptations are most beneficial to their respective interests. Mediation of this conflict is essential to the emergence of the new evolutionary unit and to its continued evolvability. As an example, we consider the transition from unicellular to multicellular organisms and study the evolution of an early-sequestered germ-line in terms of its role in mediating conflict between the two levels of selection, the cell and the cell group. We apply our theoretical framework to the evolution of germ/soma differentiation in the green algal group Volvocales. In the most complex member of the group, Volvox carteri, the potential conflicts among lower-level cells as to the "right" to reproduce the higher-level individual (i.e. the colony) have been mediated by restricting immortality and totipotency to the germ-line. However, this mediation, and the evolution of an early segregated germ-line, was achieved by suppressing mitotic and differentiation capabilities in all post-embryonic cells. By handicapping the soma in this way, individuality is ensured, but the solution has affected the long-term evolvability of this lineage. We think that although conflict mediation is pivotal to the emergence of individuality at the higher-level, the way in which the mediation is achieved can greatly affect the longer-term evolvability of the lineage.}, } @article {pmid12689678, year = {2003}, author = {Hernandez, CJ and Beaupré, GS and Carter, DR}, title = {A theoretical analysis of the changes in basic multicellular unit activity at menopause.}, journal = {Bone}, volume = {32}, number = {4}, pages = {357-363}, doi = {10.1016/s8756-3282(03)00037-1}, pmid = {12689678}, issn = {8756-3282}, mesh = {Bone Density/physiology ; Bone Remodeling/*physiology ; Humans ; Menopause/*physiology ; Middle Aged ; *Models, Biological ; Osteoporosis, Postmenopausal/etiology ; Time Factors ; }, abstract = {Bone loss at menopause is an important contributor to the development of osteoporosis in women. Although alterations in bone remodeling are the implied process through which bone is lost at menopause, how menopause influences basic multicellular units (BMUs), the teams of cells that perform bone remodeling, is not completely clear. In this analysis we utilize a computer simulation of BMU activity to evaluate the changes that occur at menopause. Transient and maintained changes in both the rate of bone turnover (expressed as the BMU birthrate or origination frequency) and the focal bone balance (differences between the amount of bone formed and resorbed at each remodeling site) are considered. The magnitude of the change in BMU activity is determined parametrically through comparison to lumbar spine bone mineral density data present in the literature. We find that a change in bone turnover that is maintained after menopause, a transient change in focal bone balance at menopause, or a combination of the two is consistent with bone loss patterns seen clinically. Understanding the changes in BMU activity that occur at menopause could lead to improved strategies to treat and prevent postmenopausal osteoporosis.}, } @article {pmid12676321, year = {2003}, author = {Coutinho, CC and Fonseca, RN and Mansure, JJ and Borojevic, R}, title = {Early steps in the evolution of multicellularity: deep structural and functional homologies among homeobox genes in sponges and higher metazoans.}, journal = {Mechanisms of development}, volume = {120}, number = {4}, pages = {429-440}, doi = {10.1016/s0925-4773(03)00007-8}, pmid = {12676321}, issn = {0925-4773}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Cell Differentiation ; Cell Division ; Cell Line ; Cell Lineage ; Down-Regulation ; Genes, Reporter ; Homeodomain Proteins/*chemistry/*genetics ; Humans ; K562 Cells ; Kruppel-Like Transcription Factors ; Luciferases/metabolism ; Mice ; Models, Genetic ; Molecular Sequence Data ; Nerve Tissue Proteins/metabolism ; Oncogene Proteins/*genetics ; Phylogeny ; Porifera ; Promoter Regions, Genetic ; Protein Binding ; Proto-Oncogene Proteins ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Transcription Factors/metabolism ; }, abstract = {The sponge homeobox gene EmH-3 had not been attributed to any homeobox family. Comparative promoter and homeodomain sequence analyses suggest that it is related to the Hox11 gene, which belongs to the Tlx homeobox family. Hox11 is highly expressed in proliferating progenitor cells, but expression is downregulated during cell differentiation. Using reporter gene methodology, we monitored function of the sponge EmH-3 promoter transfected into human erythroleukemia K562 cells. These cells express the Tlx/Hox11 gene constitutively, and downregulate its expression upon differentiation. The same pattern of expression and downregulation was observed for the sponge reporter construct. We propose that Tlx/Hox11 genes have structural and functional homologies conserved in phylogenetically distant groups, that represent a deep homology in the regulation of cell proliferation, commitment and differentiation.}, } @article {pmid12672462, year = {2003}, author = {Maytal-Kivity, V and Pick, E and Piran, R and Hofmann, K and Glickman, MH}, title = {The COP9 signalosome-like complex in S. cerevisiae and links to other PCI complexes.}, journal = {The international journal of biochemistry & cell biology}, volume = {35}, number = {5}, pages = {706-715}, doi = {10.1016/s1357-2725(02)00378-3}, pmid = {12672462}, issn = {1357-2725}, mesh = {Amino Acid Sequence ; COP9 Signalosome Complex ; Cysteine Endopeptidases/genetics ; DNA-Binding Proteins/*chemistry/genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; Microscopy, Fluorescence ; Molecular Sequence Data ; Multienzyme Complexes/genetics ; Multiprotein Complexes ; Peptide Hydrolases ; Phylogeny ; Proteasome Endopeptidase Complex ; Proteins/*chemistry/genetics ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/*chemistry/genetics ; Saccharomycetales/*genetics ; Sequence Alignment ; Sequence Homology ; Transcription Factors/*chemistry/genetics ; Ubiquitin/genetics ; }, abstract = {The COP9 signalosome (CSN), the lid subcomplex of the proteasome and translational initiation factor 3 (eIF3) share structural similarities and are often referred to as the PCI family of complexes. In multicellular eukaryotes, the CSN is highly conserved as an 8-subunit complex but in Saccharomyces cerevisiae the complex is rather divergent. We further characterize the composition and properties of the CSN in budding yeast and its interactions with these related complexes. Using the generalized profile method we identified CSN candidates, four with PCI domains: Csn9, Csn10, Pci8/Csn11, and Csn12, and one with an MPN domain, Csn5/Rri1. These proteins and an additional interactor, Csi1, were tested for pairwise interactions by yeast two-hybrid and were found to form a cluster surrounding Csn12. Csn5 and Csn12 cofractionate in a complexed form with an apparent molecular weight of roughly 250kDa. However, Csn5 migrates as a monomer in Deltacsn12 supporting the pivotal role of Csn12 in stabilizing the complex. Confocal fluorescence microscopy detects GFP-tagged Csn5 preferentially in the nucleus, whereas in absence of Csn12, Csn10, Pci8/Csn11, or Csi1, Csn5 is delocalized throughout the cell, indicating that multiple subunits are required for nuclear localization of Csn5. Two CSN subunits, Csn9 and Csi1, interact with the proteasome lid subunit Rpn5. Pci8/Csn11 has previously been shown to interact with eIF3. Together, these results point to a network of interactions between these three structurally similar, yet functionally diverse, complexes.}, } @article {pmid12670511, year = {2003}, author = {Debrabant, A and Lee, N and Bertholet, S and Duncan, R and Nakhasi, HL}, title = {Programmed cell death in trypanosomatids and other unicellular organisms.}, journal = {International journal for parasitology}, volume = {33}, number = {3}, pages = {257-267}, doi = {10.1016/s0020-7519(03)00008-0}, pmid = {12670511}, issn = {0020-7519}, mesh = {Amphotericin B/therapeutic use ; Animals ; Antimony Sodium Gluconate/therapeutic use ; Antiprotozoal Agents/therapeutic use ; Apoptosis/*physiology ; Bacteria/cytology ; Dinoflagellida/cytology ; Eukaryota/cytology/growth & development ; Leishmania/cytology ; Leishmaniasis/drug therapy ; Life Cycle Stages ; Plasmodium/cytology ; Trypanosoma/*cytology/growth & development ; Yeasts/cytology ; }, abstract = {In multicellular organisms, cellular growth and development can be controlled by programmed cell death (PCD), which is defined by a sequence of regulated events. However, PCD is thought to have evolved not only to regulate growth and development in multicellular organisms but also to have a functional role in the biology of unicellular organisms. In protozoan parasites and in other unicellular organisms, features of PCD similar to those in multicellular organisms have been reported, suggesting some commonality in the PCD pathway between unicellular and multicellular organisms. However, more extensive studies are needed to fully characterise the PCD pathway and to define the factors that control PCD in the unicellular organisms. The understanding of the PCD pathway in unicellular organisms could delineate the evolutionary origin of this pathway. Further characterisation of the PCD pathway in the unicellular parasites could provide information regarding their pathogenesis, which could be exploited to target new drugs to limit their growth and treat the disease they cause.}, } @article {pmid12668594, year = {2003}, author = {Ibañez-Tallon, I and Heintz, N and Omran, H}, title = {To beat or not to beat: roles of cilia in development and disease.}, journal = {Human molecular genetics}, volume = {12 Spec No 1}, number = {}, pages = {R27-35}, doi = {10.1093/hmg/ddg061}, pmid = {12668594}, issn = {0964-6906}, mesh = {Animals ; Body Patterning ; Cilia/*physiology/ultrastructure ; Cornea/physiology ; Dyneins/physiology ; Ependyma/physiology ; Fallopian Tube Diseases/pathology ; Female ; Flagella/physiology/ultrastructure ; Humans ; Male ; Mice ; Models, Anatomic ; Models, Biological ; Spermatozoa/abnormalities ; }, abstract = {Cilia and flagella appeared very early in evolution to provide unicellular organisms with motility in water. Adaptation to non-aquatic life in plants resulted in the almost complete elimination of these organelles, except for gametic transport in some phylogenetic groups. In contrast, cilia and flagella were retained and employed for a wide variety of functions requiring fluid movement in complex multicellular animals. The functions of cilia in diverse processes such as left-right axis pattern formation, cerebrospinal fluid flow, sensory reception, mucociliary clearance and renal physiology indicate that cilia have been adapted as versatile tools for many biological processes. In this review, we discuss recent discoveries that have extended knowledge of the roles of cilia in normal development, and the pathological consequences caused by their dysfunction in mammals. We also consider evolutionary relationships between cilia from lower and higher eukaryotes, outline the ciliary components required for assembly and motility, and review the terminology of axonemal heavy chain dynein genes.}, } @article {pmid12617817, year = {2002}, author = {Tanaka, SS and Matsui, Y}, title = {Developmentally regulated expression of mil-1 and mil-2, mouse interferon-induced transmembrane protein like genes, during formation and differentiation of primordial germ cells.}, journal = {Gene expression patterns : GEP}, volume = {2}, number = {3-4}, pages = {297-303}, doi = {10.1016/s0925-4773(02)00384-2}, pmid = {12617817}, issn = {1567-133X}, mesh = {Animals ; Antigens, Differentiation ; Base Sequence ; Blotting, Southern ; Cell Differentiation/*physiology ; Cell Movement ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Germ Cells/*metabolism ; In Situ Hybridization, Fluorescence ; Membrane Proteins/biosynthesis/*genetics ; Mice/embryology ; Molecular Sequence Data ; RNA-Binding Proteins/genetics ; Sequence Alignment ; }, abstract = {In all multicellular organisms, germ cells originating from a fertilized egg have the highly specialized role of transmitting genetic information to the next generation. In many animal species, the establishment of the germ cell lineage is regulated by the maternally inherited germplasm. In mammals, however, germline determination is not based on the unequal distribution of maternal determinants. In the processes of mammalian germ cell formation and subsequent differentiation, the molecular basis of the acquisition of germ cell status is not well understood. Since migrating primordial germ cells (PGCs) are lineage-restricted to the germline, they have already acquired a germ cell specific fate distinct from that of pluri/multi-potent stem cells. However, there have been no molecules known to be expressed in migrating PGCs but not in the inner cell mass of blastocysts. Such molecules should be involved in early germ cell development, and they should make good markers for following the process of PGC formation. To identify such molecules, we performed a subtracted cDNA screening with migrating PGCs and blastocysts in mice, and isolated 11 clones preferentially expressed in PGCs. Here, we report the identification of two genes with similarity to human interferon-induced transmembrane protein (Ifitm) genes, and expression patterns of these genes in forming and in differentiating PGCs. During germ cell formation, mouse Ifitm like (mil)-1 was expressed in putative PGC ancestors in embryos at 6.5-7.5 days post coitum. In migrating PGCs, mil-1 expression was continuously observed and mil-2 expression was first detected during germ cell differentiation.}, } @article {pmid12615944, year = {2003}, author = {Serino, G and Su, H and Peng, Z and Tsuge, T and Wei, N and Gu, H and Deng, XW}, title = {Characterization of the last subunit of the Arabidopsis COP9 signalosome: implications for the overall structure and origin of the complex.}, journal = {The Plant cell}, volume = {15}, number = {3}, pages = {719-731}, pmid = {12615944}, issn = {1040-4651}, mesh = {Amino Acid Sequence ; Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; COP9 Signalosome Complex ; Cell Cycle Proteins/genetics/metabolism ; Cloning, Molecular ; *Cullin Proteins ; DNA, Complementary/chemistry/genetics ; *GTP-Binding Proteins ; Gene Expression Regulation, Plant ; Intracellular Signaling Peptides and Proteins ; Molecular Sequence Data ; Mutation ; Phylogeny ; Protein Binding ; Protein Interaction Mapping ; Proteins/genetics/metabolism ; *Repressor Proteins ; Saccharomyces cerevisiae/genetics ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Signal Transduction/*genetics ; Two-Hybrid System Techniques ; }, abstract = {The COP9 signalosome (CSN) is an evolutionarily conserved protein complex that resembles the lid subcomplex of proteasomes. Through its ability to regulate specific proteasome-mediated protein degradation events, CSN controls multiple aspects of development. Here, we report the cloning and characterization of AtCSN2, the last uncharacterized CSN subunit from Arabidopsis. We show that the AtCSN2 gene corresponds to the previously identified FUS12 locus and that AtCSN2 copurifies with CSN, confirming that AtCSN2 is an integral component of CSN. AtCSN2 is not only able to interact with the SCF(TIR1) subunit AtCUL1, which is partially responsible for the regulatory interaction between CSN and SCF(TIR1), but also interacts with AtCUL3, suggesting that CSN is able to regulate the activity of other cullin-based E3 ligases through conserved interactions. Phylogenetic analysis indicated that the duplication and subsequent divergence events that led to the genes that encode CSN and lid subunits occurred before the divergence of unicellular and multicellular eukaryotic organisms and that the CSN subunits were more conserved than the lid subunits during evolution. Comparative analyses of the subunit interaction of CSN revealed a set of conserved subunit contacts and resulted in a model of CSN subunit topology, some aspects of which were substantiated by in vivo cross-link tests.}, } @article {pmid12615210, year = {2003}, author = {Vanlandschoot, P and Leroux-Roels, G}, title = {Viral apoptotic mimicry: an immune evasion strategy developed by the hepatitis B virus?.}, journal = {Trends in immunology}, volume = {24}, number = {3}, pages = {144-147}, doi = {10.1016/s1471-4906(03)00026-7}, pmid = {12615210}, issn = {1471-4906}, mesh = {*Apoptosis ; Complement System Proteins/immunology ; Hepatitis B Surface Antigens/immunology/metabolism ; Hepatitis B virus/*immunology/*metabolism ; Protein Binding ; Viral Envelope Proteins/immunology ; }, abstract = {The co-existence of viruses and organisms for millions of years has influenced the evolution of both. Various viral strategies to enter a host and take over the control of cells to produce virus progeny have developed. Several antiviral (immune) responses have also been developed. The apoptotic death program is a conserved feature of eukaryotic cells. In multicellular organisms the binding and engulfment of apoptotic material is considered to be the end stage of the apoptotic process. Because of its importance, it seems probable that viruses have targeted this ancient removal system to suppress immune responses and to establish or maintain infection. The possibility that the hepatitis B virus has evolved such a mechanism, termed "viral apoptotic-like mimicry", is presented here.}, } @article {pmid12597116, year = {2003}, author = {Jockusch, H and Dress, A}, title = {From sphere to torus: a topological view of the metazoan body plan.}, journal = {Bulletin of mathematical biology}, volume = {65}, number = {1}, pages = {57-65}, doi = {10.1006/bulm.2002.0319}, pmid = {12597116}, issn = {0092-8240}, mesh = {Animals ; *Biological Evolution ; *Body Patterning ; Epithelium/anatomy & histology ; Image Processing, Computer-Assisted/*methods ; Models, Biological ; }, abstract = {From the viewpoint of mathematical topology, membrane systems in intact living cells can be described as closed and orientable surfaces, i.e., as surfaces with two sides and no boundary lines so that an 'inside' and an 'outside' can be distinguished. Usually, biomembranes represent topological spheres, often one embedded in another one. Toroidal membranes are occasionally observed, e.g., in specialized structures of plant cells like the prolamellar body. Here, we propose that rules analogous to those that govern the topology of biomembranes hold for the epithelial cell sheets that cover anatomically external as well as internal surfaces of multicellular animals. We suggest to study the emergence of morphological complexity during metazoan development using concepts from mathematical topology, and propose experimental analyses of those topological transitions that appear to be relevant in development and evolution.}, } @article {pmid12595122, year = {2003}, author = {Teuscher, C and Mange, D and Stauffer, A and Tempesti, G}, title = {Bio-inspired computing tissues: towards machines that evolve, grow, and learn.}, journal = {Bio Systems}, volume = {68}, number = {2-3}, pages = {235-244}, doi = {10.1016/s0303-2647(02)00100-4}, pmid = {12595122}, issn = {0303-2647}, mesh = {Cell Differentiation ; *Computational Biology ; Phylogeny ; }, abstract = {Biological inspiration in the design of computing machines could allow the creation of new machines with promising characteristics such as fault-tolerance, self-replication or cloning, reproduction, evolution, adaptation and learning, and growth. The aim of this paper is to introduce bio-inspired computing tissues that might constitute a key concept for the implementation of 'living' machines. We first present a general overview of bio-inspired systems and the POE model that classifies bio-inspired machines along three axes. The Embryonics project--inspired by some of the basic processes of molecular biology--is described by means of the BioWatch application, a fault-tolerant and self-repairable watch. The main characteristics of the Embryonics project are the multicellular organization, the cellular differentiation, and the self-repair capabilities. The BioWall is intended as a reconfigurable computing tissue, capable of interacting with its environment by means of a large number of touch-sensitive elements coupled with a color display. For illustrative purposes, a large-scale implementation of the BioWatch on the BioWall's computational tissue is presented. We conclude the paper with a description of bio-inspired computing tissues and POEtic machines.}, } @article {pmid12594919, year = {2003}, author = {Herrmann, RG and Maier, RM and Schmitz-Linneweber, C}, title = {Eukaryotic genome evolution: rearrangement and coevolution of compartmentalized genetic information.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {358}, number = {1429}, pages = {87-97; discussion 97}, pmid = {12594919}, issn = {0962-8436}, mesh = {Atropa belladonna/cytology/genetics ; Eukaryotic Cells/cytology/*metabolism ; *Evolution, Molecular ; *Genome ; Plants/*genetics ; Plastids/genetics ; RNA Editing ; Tobacco/cytology/genetics ; Transcription, Genetic ; }, abstract = {The plant cell operates with an integrated, compartmentalized genome consisting of nucleus/cytosol, plastids and mitochondria that, in its entirety, is regulated in time, quantitatively, in multicellular organisms and also in space. This genome, as do genomes of eukaryotes in general, originated in endosymbiotic events, with at least three cells, and was shaped phylogenetically by a massive and highly complex restructuring and intermixing of the genetic potentials of the symbiotic partners and by lateral gene transfer. This was accompanied by fundamental changes in expression signals in the entire system at almost all regulatory levels. The gross genome rearrangements contrast with a highly specific compartmental interplay, which becomes apparent in interspecific nuclear-plastid cybrids or hybrids. Organelle exchanges, even between closely related species, can greatly disturb the intracellular genetic balance ("hybrid bleaching"), which is indicative of compartmental coevolution and is of relevance for speciation processes. The photosynthetic machinery of plastids, which is embedded in that genetic machinery, is an appealing model to probe into genomic and organismic evolution and to develop functional molecular genomics. We have studied the reciprocal Atropa belladonna-Nicotiana tabacum cybrids, which differ markedly in their phenotypes, and found that transcriptional and post-transcriptional processes can contribute to genome/plastome incompatibility. Allopolyploidy can influence this phenomenon by providing an increased, cryptic RNA editing potential and the capacity to maintain the integrity of organelles of different taxonomic origins.}, } @article {pmid12581626, year = {2003}, author = {Trosko, JE}, title = {Human stem cells as targets for the aging and diseases of aging processes.}, journal = {Medical hypotheses}, volume = {60}, number = {3}, pages = {439-447}, doi = {10.1016/s0306-9877(02)00446-2}, pmid = {12581626}, issn = {0306-9877}, support = {2 P42 ES04911-12/ES/NIEHS NIH HHS/United States ; }, mesh = {*Aging ; Apoptosis ; Cell Communication ; Cell Division ; Disease Progression ; Extracellular Matrix/metabolism ; Humans ; Models, Biological ; Models, Theoretical ; Stem Cells/*cytology/metabolism ; }, abstract = {While many theories have been proposed for the aging process, and many debates on the matter of aging and the diseases of aging being either the result of the same or independent processes, most have not considered humans as a hierarchical system made up of cybernetically interacting levels of organization. To understand the aging process and the diseases of aging, one must view the human as the result of the total genomic DNA in the single fertilized egg that proliferates, differentiates and develops into an individual of about 100 trillion cells, organized by different cell types (pluri-potent stem cells, progenitor stem cells, terminally differentiated cells) into multiple tissue, organ and organ systems which interact with each other via endogenous factors and with exogenous factors. Our hypothesis is that both aging and diseases of aging are dependent of the normal functioning of the pluri-potent stem cell pool. Specifically, the concept involves the cybernetic feedback between the 'quantity' of the stem cell pool in each tissue niche with the 'quality' of the stem cells in the pool. The process of gap junctional inter-cellular communication (GJIC), which has been implicated in the evolution from the single cell organism to the multi-cellular organisms, requiring growth control, differentiation, apoptosis, adaptive response capability of differentiated cells and senescence, is speculated to be a shared mechanism in stem cell biology and in many chronic disease processes (teratogenesis; carcinogenesis, atherogenesis, diabetigenesis, etc.). Specifically, stem cells are assumed to be 'immortal' until induced to express their connexin genes and have functional GJIC, at which time they can differentiate and become 'mortal'. As long as the stem cells are communicating with their differentiated daughters via some extra-cellular soluble negative growth factor, the homeostatic control of their growth and differentiation is maintained for the organism. However, if the stem cell pool is depleted by any process, replacement of tissue due to wear and tear is diminished. The dependence of this tissue/organ to maintain homeostatic control of other organ systems then diminishes, leading to 'systems failure'. In addition, if the stem cells in the pool have been exposed to agents that prevent the normal terminal differentiation of that cell, but whereby these 'initiated' stem cells can be expanded in any tissue, clones of partially differentiated and non-functional appear in the tissue. This diminishes the efficacy of that tissue to function properly and, thereby, also contributes to 'system failure' by contributing to the breakdown of homeostatic organ system control. One clear example, that of carcinogenesis, illustrates this point.}, } @article {pmid12568336, year = {2002}, author = {Winckler, T and Dingermann, T and Glöckner, G}, title = {Dictyostelium mobile elements: strategies to amplify in a compact genome.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {59}, number = {12}, pages = {2097-2111}, doi = {10.1007/s000180200010}, pmid = {12568336}, issn = {1420-682X}, mesh = {Animals ; *DNA Transposable Elements ; Dictyostelium/*genetics ; Genes, Protozoan ; Genome, Protozoan ; Open Reading Frames ; Phylogeny ; RNA, Transfer/genetics ; *Retroelements ; }, abstract = {Dictyostelium discoideum is a eukaryotic microorganism that is attractive for the study of fundamental biological phenomena such as cell-cell communication, formation of multicellularity, cell differentiation and morphogenesis. Large-scale sequencing of the D. discoideum genome has provided new insights into evolutionary strategies evolved by transposable elements (TEs) to settle in compact microbial genomes and to maintain active populations over evolutionary time. The high gene density (about 1 gene/2.6 kb) of the D. discoideum genome leaves limited space for selfish molecular invaders to move and amplify without causing deleterious mutations that eradicate their host. Targeting of transfer RNA (tRNA) gene loci appears to be a generally successful strategy for TEs residing in compact genomes to insert away from coding regions. In D. discoideum, tRNA gene-targeted retrotransposition has evolved independently at least three times by both non-long terminal repeat (LTR) retrotransposons and retrovirus-like LTR retrotransposons. Unlike the nonspecifically inserting D. discoideum TEs, which have a strong tendency to insert into preexisting TE copies and form large and complex clusters near the ends of chromosomes, the tRNA gene-targeted retrotransposons have managed to occupy 75% of the tRNA gene loci spread on chromosome 2 and represent 80% of the TEs recognized on the assembled central 6.5-Mb part of chromosome 2. In this review we update the available information about D. discoideum TEs which emerges both from previous work and current large-scale genome sequencing, with special emphasis on the fact that tRNA genes are principal determinants of retrotransposon insertions into the D. discoideum genome.}, } @article {pmid12559395, year = {2003}, author = {Horiuchi, Y and Kimura, R and Kato, N and Fujii, T and Seki, M and Endo, T and Kato, T and Kawashima, K}, title = {Evolutional study on acetylcholine expression.}, journal = {Life sciences}, volume = {72}, number = {15}, pages = {1745-1756}, doi = {10.1016/s0024-3205(02)02478-5}, pmid = {12559395}, issn = {0024-3205}, mesh = {Acetylcholine/*biosynthesis/*genetics ; Animals ; Bacteria/*metabolism ; *Biological Evolution ; Chromatography, High Pressure Liquid ; Electrochemistry ; Fungi/*metabolism ; Invertebrates/*metabolism ; Plants/*metabolism ; Radioimmunoassay ; }, abstract = {Acetylcholine (ACh) is a well-known neurotransmitter in the cholinergic nervous systems of vertebrates and insects; however, there is only indirect evidence for its presence in lower invertebrates, such as plants and fungi. We therefore investigated the expression of ACh in invertebrates (sea squirt, sea urchin, trepang, squid, abalone, nereis, sea anemone, coral and sponge), plants (arabidopsis, eggplant, bamboo shoot, cedar, hinoki, pine, podcarp, fern, horsetail and moss), fungi (yeast and mushroom) and bacteria by assaying ACh content and synthesis, focusing on the presence of two synthetic enzymes, choline acetyltransferase (ChAT) and carnitine acetyltransferase (CarAT). Using a specific radioimmunoassay, ACh was detected in all samples tested. The levels varied considerably, however, with the upper portion of bamboo shoots having the highest content (2.9 micromol/g). ACh synthesis was also detected in all samples tested; moreover, the activity in most samples from the animal kingdom, as well as bamboo shoots and the stem of the shiitake mushroom, were sensitive to both ChAT and CarAT inhibitors. Levels of ACh synthesis were lower in samples from other plants, fungi and bacteria and were insensitive to ChAT and CarAT inhibitors. These findings demonstrate the presence of ACh and ACh-synthesizing activity in evolutionally primitive life as well as in more complex multicellular organisms. In the context of the recent discovery of non-neuronal ACh in various mammalian species, these findings suggest that ACh been expressed in organisms from the beginning of life, functioning as a local mediator as well as a neurotransmitter.}, } @article {pmid12552117, year = {2003}, author = {Burger, G and Forget, L and Zhu, Y and Gray, MW and Lang, BF}, title = {Unique mitochondrial genome architecture in unicellular relatives of animals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {100}, number = {3}, pages = {892-897}, pmid = {12552117}, issn = {0027-8424}, mesh = {Amino Acid Motifs ; Animals ; Base Sequence ; Chromosomes/ultrastructure ; DNA, Mitochondrial/*genetics ; Electrophoresis, Agar Gel ; *Genome ; Genome, Bacterial ; Genome, Fungal ; Genome, Plant ; Humans ; Introns ; Models, Genetic ; Molecular Sequence Data ; Open Reading Frames ; Phylogeny ; }, abstract = {Animal mtDNAs are typically small (approximately 16 kbp), circular-mapping molecules that encode 37 or fewer tightly packed genes. Here we investigate whether similarly compact mitochondrial genomes are also present in the closest unicellular relatives of animals, i.e., choanoflagellate and ichthyosporean protists. We find that the gene content and architecture of the mitochondrial genomes of the choanoflagellate Monosiga brevicollis, the ichthyosporean Amoebidium parasiticum, and Metazoa are radically different from one another. The circular-mapping choanoflagellate mtDNA with its long intergenic regions is four times as large and contains two times as many protein genes as do animal mtDNAs, whereas the ichthyosporean mitochondrial genome totals >200 kbp and consists of several hundred linear chromosomes that share elaborate terminal-specific sequence patterns. The highly peculiar organization of the ichthyosporean mtDNA raises questions about the mechanism of mitochondrial genome replication and chromosome segregation during cell division in this organism. Considering that the closest unicellular relatives of animals possess large, spacious, gene-rich mtDNAs, we posit that the distinct compaction characteristic of metazoan mitochondrial genomes occurred simultaneously with the emergence of a multicellular body plan in the animal lineage.}, } @article {pmid12548541, year = {2003}, author = {Schneider, SQ and Finnerty, JR and Martindale, MQ}, title = {Protein evolution: structure-function relationships of the oncogene beta-catenin in the evolution of multicellular animals.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {295}, number = {1}, pages = {25-44}, doi = {10.1002/jez.b.6}, pmid = {12548541}, issn = {1552-5007}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Conserved Sequence ; Cytoskeletal Proteins/*chemistry/genetics/*metabolism ; *Evolution, Molecular ; Gene Duplication ; Genomics ; Models, Molecular ; Mutation ; Phylogeny ; Protein Structure, Tertiary ; Sequence Analysis, DNA ; Species Specificity ; Structure-Activity Relationship ; Trans-Activators/*chemistry/genetics/*metabolism ; beta Catenin ; }, abstract = {Beta-catenin functions as a cytoskeletal linker protein in cadherin-mediated adhesion and as a signal mediator in wnt-signal transduction pathways. We use a novel integrative approach, combining evolutionary, genomic, and three-dimensional structural data to analyze and trace the structural and functional evolution of beta-catenin genes. This approach also enabled us to examine the effects of gene duplication on the structure and function of beta-catenin genes in Drosophila, C. elegans, and vertebrates. By sampling a large number of different taxa, we identified both ancestral and derived motifs and residues within the different regions of the beta-catenin proteins. Projecting amino acid substitutions onto the three- dimensional structure established for mouse beta-catenin, we identified specific domains that exhibit loss and gain of selective constraints during beta catenin evolution. Structural changes, changes in the amino acid substitution rate, and the appearance of novel functional domains in beta-catenin can be mapped to specific branches on the metazoan tree. Together, our analyses suggest that a single, beta-catenin gene fulfilled both adhesion and signaling functions in the last common ancestor of metazoans some 700 million years ago. In addition, gene duplications facilitated the evolution of beta-catenins with novel functions and allowed the evolution of multiple, single-function proteins (cell adhesion or wnt-signaling) from the ancestral, dual-function protein. Integrative methods such as those we have applied here, utilizing the 'natural experiments' present in animal diversity, can be employed to identify novel and shared functional motifs and residues in virtually any protein among the proteomes of model systems and humans.}, } @article {pmid12547910, year = {2003}, author = {Pfeiffer, T and Bonhoeffer, S}, title = {An evolutionary scenario for the transition to undifferentiated multicellularity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {100}, number = {3}, pages = {1095-1098}, pmid = {12547910}, issn = {0027-8424}, mesh = {Adenosine Triphosphate/metabolism ; *Biological Evolution ; Cell Aggregation ; Cell Differentiation ; Cell Movement ; Computer Simulation ; Fermentation ; *Models, Biological ; Reproduction/physiology ; }, abstract = {The evolutionary transition from single cells toward multicellular forms of life represents one of the major transitions in the evolution of complex organisms. In this transition, single autonomously reproducing cells became parts of larger reproducing entities that eventually constituted a new unit of selection. The first step in the evolutionary transition to multicellularity likely was the evolution of simple, undifferentiated cell clusters. However, what the selective advantage of such cell clusters may have been remains unclear. Here, we argue that in populations of unicellular organisms with cooperative behavior, clustering may be beneficial by reducing interactions with noncooperative individuals. In support of this hypothesis, we present a set of computer simulations showing that clustering can evolve as a biological, heritable trait for cells that cooperate in the use of external energy resources. Following the evolution of simple cell clusters, further benefits could have arisen from the exchange of resources between cells of a cluster.}, } @article {pmid12546676, year = {2003}, author = {Rose, SP}, title = {Communication: from neurons to people; from present to future.}, journal = {Biochemical Society transactions}, volume = {31}, number = {Pt 1}, pages = {159-161}, doi = {10.1042/bst0310159}, pmid = {12546676}, issn = {0300-5127}, mesh = {Animals ; Biochemistry/*trends ; Biological Evolution ; Cell Communication ; Communication ; Humans ; Neurons/metabolism/*physiology ; Proteome ; *Signal Transduction ; }, abstract = {From its emergence out of organic chemistry and physiology a century ago, the history of biochemistry is one of shifting research agendas. For organic chemists, the questions were those of structure and composition, while for physiologists, they were questions of function. The dynamic biochemistry of the mid-20th century centred on catalysis, energy flow and metabolism. The emergence of molecular biology ('practising biochemistry without a licence') introduced information in place of energy as an organizing cellular principle, but in doing so forgot dynamics. For Crick's Central Dogma, information -- signals -- flowed in one direction only. Now, proteomics is enabling molecular biologists to rediscover biochemistry once more. Signalling -- the processes of communication across space and time -- occurs at all biological levels. I will review them, and their potential future. Will the metaphor of signalling provide a new organizing principle, one that recognizes the essentially interactive nature of information flow within metabolic webs?: I discuss first, the conservation of signalling molecules at the cellular level over evolutionary time; secondly, the supracellular level of physiological signalling in multicellular organisms -- hormones and neurons; thirdly, supraorganismic signalling and communication -- from pheromones to speech; and finally, signalling and reception within and outside the biochemical community - how do we/can we communicate with one another and the rest of the world?}, } @article {pmid12546065, year = {2002}, author = {Messer, W and Zakrzewska-Czerwińska, J}, title = {Streptomyces and Escherichia coli, model organisms for the analysis of the initiation of bacterial chromosome replication.}, journal = {Archivum immunologiae et therapiae experimentalis}, volume = {50}, number = {6}, pages = {393-398}, pmid = {12546065}, issn = {0004-069X}, mesh = {Bacterial Proteins/metabolism ; Chromosomes, Bacterial/*genetics ; *DNA Replication ; DNA-Binding Proteins/metabolism ; Escherichia coli/*genetics ; Replication Origin ; Streptomyces/*genetics ; }, abstract = {Streptomyces coelicolor A3(2) and Escherichia coli are quite different in their life-style and the structures of their genomes. Streptomyces exhibit complex multicellular development including formation of multigenomic hyphae during growth. These organisms possess a large linear (8.7 Mb) and GC-rich (approximately 72%) chromosome. The genome sequence of S. coelicolor has just been completed. The difference between E. coli and Streptomyces making them an excellent model organisms for a comparison of their replication modes. In this review, we compare initiation of chromosome replication in both organisms. Their replication origins are different in size, but both have DnaA boxes--a binding motifs for initiator DnaA protein. The two DnaA proteins have practically the same biochemical properties. Many aspects of the control of initiation seem to be similar. A comparison of the two systems thus allows us to define those aspects of replication initiation that are universally used in the eubacterial kingdom.}, } @article {pmid12543972, year = {2003}, author = {Zeyl, C and Vanderford, T and Carter, M}, title = {An evolutionary advantage of haploidy in large yeast populations.}, journal = {Science (New York, N.Y.)}, volume = {299}, number = {5606}, pages = {555-558}, doi = {10.1126/science.1078417}, pmid = {12543972}, issn = {1095-9203}, mesh = {*Adaptation, Physiological ; Analysis of Variance ; *Biological Evolution ; Diploidy ; Genes, Dominant ; Genes, Fungal ; Genes, Recessive ; *Haploidy ; Heterozygote ; Homozygote ; Models, Biological ; Mutation ; Reproduction ; Saccharomyces cerevisiae/*genetics/*physiology ; }, abstract = {Although seed plants and multicellular animals are predominantly diploid, the prominence of diploidy varies greatly among eukaryote life cycles, and no general evolutionary advantage of diploidy has been demonstrated. By doubling the copy number of each gene, diploidy may increase the rate at which adaptive mutations are produced. However, models suggest that this does not necessarily accelerate adaptation by diploid populations. We tested model predictions regarding rates of adaptation using asexual yeast populations. Adaptive mutations were on average partially recessive. As predicted, diploidy slowed adaptation by large populations but not by small populations.}, } @article {pmid12543256, year = {2003}, author = {Campisi, J}, title = {Cellular senescence and apoptosis: how cellular responses might influence aging phenotypes.}, journal = {Experimental gerontology}, volume = {38}, number = {1-2}, pages = {5-11}, doi = {10.1016/s0531-5565(02)00152-3}, pmid = {12543256}, issn = {0531-5565}, mesh = {Aged ; Aging/*physiology ; Animals ; Apoptosis/*physiology ; Cellular Senescence/*physiology ; Gene Expression Regulation ; Genes, Tumor Suppressor ; Humans ; Mammals/*physiology ; Multifactorial Inheritance ; Neoplasms/genetics/pathology ; }, abstract = {Aging in complex multi-cellular organisms such as mammals entails distinctive changes in cells and molecules that ultimately compromise the fitness of adult organisms. These cellular and molecular changes lead to the phenotypes we recognize as aging. This review discusses some of the cellular and molecular changes that occur with age, specifically changes that occur as a result of cellular responses that evolved to ameliorate the inevitable damage that is caused by endogenous and environmental insults. Because the force of natural selection declines with age, it is likely that these processes were never optimized during their evolution to benefit old organisms. That is, some age-related changes may be the result of gene activities that were selected for their beneficial effects in young organisms, but the same gene activities may have unselected, deleterious effects in old organisms, a phenomenon termed antagonistic pleiotropy. Two cellular processes, apoptosis and cellular senescence, may be examples of antagonistic pleiotropy. Both processes are essential for the viability and fitness of young organisms, but may contribute to aging phenotypes, including certain age-related diseases.}, } @article {pmid12539240, year = {2003}, author = {Boot-Handford, RP and Tuckwell, DS}, title = {Fibrillar collagen: the key to vertebrate evolution? A tale of molecular incest.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {25}, number = {2}, pages = {142-151}, doi = {10.1002/bies.10230}, pmid = {12539240}, issn = {0265-9247}, mesh = {Amino Acid Sequence ; Animals ; Collagen/chemistry/*genetics/*metabolism ; *Evolution, Molecular ; Gene Duplication ; Invertebrates ; Models, Biological ; Molecular Sequence Data ; Phylogeny ; Sequence Homology, Amino Acid ; Vertebrates ; }, abstract = {Fibril-forming (fibrillar) collagens are extracellular matrix proteins conserved in all multicellular animals. Vertebrate members of the fibrillar collagen family are essential for the formation of bone and teeth, tissues that characterise vertebrates. The potential role played by fibrillar collagens in vertebrate evolution has not been considered previously largely because the family has been around since the sponge and it was unclear precisely how and when those particular members now found in vertebrates first arose. We present evidence that the classical vertebrate fibrillar collagens share a single common ancestor that arose at the very dawn of the vertebrate world and prior to the associated genome duplication events. Furthermore, we present a model, 'molecular incest', that not only accounts for the characteristics of the modern day vertebrate fibrillar collagen family but demonstrates the specific effects genome or gene duplications may have on the evolution of multimeric proteins in general.}, } @article {pmid12532263, year = {2003}, author = {Rantanen, A and Gaspari, M and Falkenberg, M and Gustafsson, CM and Larsson, NG}, title = {Characterization of the mouse genes for mitochondrial transcription factors B1 and B2.}, journal = {Mammalian genome : official journal of the International Mammalian Genome Society}, volume = {14}, number = {1}, pages = {1-6}, doi = {10.1007/s00335-002-2218-z}, pmid = {12532263}, issn = {0938-8990}, mesh = {Animals ; Chromosome Mapping ; Mice ; Mitochondria/*genetics/metabolism ; Molecular Sequence Data ; Phylogeny ; Promoter Regions, Genetic ; Synteny ; Transcription Factors/*genetics/metabolism ; }, abstract = {We have recently fully reconstituted the basal human mitochondrial transcription machinery in a pure in vitro system. Surprisingly, we found two different transcription factors (TFB1M and TFB2M) that each interact with mitochondrial RNA polymerase in human mitochondria, whereas there is only one such factor in budding yeast mitochondria. This unexpected finding raised important questions concerning the regulation of mitochondrial transcription in mammals in general and in other metazoans. We have now further analyzed putative homologs to TFB1M and TFB2M in different species. We mapped the mouse homologs, Tfb1m and Tfb2m, by linkage analysis to mouse Chr 17 and Chr 1, respectively. These regions display conserved linkage synteny with human Chr 6 and Chr 1, where TFB1M and TFB2M map. The intron-exon arrangements of Tfb1m and TFB1M and of Tfb2m and TFB2M were identical, and the promoter regions had similar predicted recognition elements for transcriptional factors NRF2 and Sp1. Northern blot analyses showed that Tfb1m and Tfb2m were ubiquitously expressed and had expression patterns that were very similar to the previously reported expression patterns for TFB1M and TFB2M. These findings show that Tfb1m and Tfb2m indeed are orthologs to TFB1M and TFB2M. Bioinformatic analyses indicated that most metazoans have two TFBM genes, since putative homologs to both TFB1M and TFB2M were found in D. melanogaster. Our data thus suggest that a duplication event of the TFBM gene in early metazoan evolution has permitted a more flexible regulation of mtDNA transcription, possibly in response to the complex physiological demands of multicellular organisms.}, } @article {pmid12526848, year = {2003}, author = {Lalucque, H and Silar, P}, title = {NADPH oxidase: an enzyme for multicellularity?.}, journal = {Trends in microbiology}, volume = {11}, number = {1}, pages = {9-12}, doi = {10.1016/s0966-842x(02)00007-0}, pmid = {12526848}, issn = {0966-842X}, mesh = {Amino Acid Sequence ; Ascomycota/genetics/isolation & purification/physiology ; Eukaryotic Cells/physiology ; Humans ; Molecular Sequence Data ; NADPH Oxidases/genetics/*physiology ; Phylogeny ; Sequence Alignment ; Sequence Homology, Amino Acid ; Signal Transduction ; }, abstract = {Multicellularity has evolved several times during the evolution of eukaryotes. One evolutionary pressure that permits multicellularity relates to the division of work, where one group of cells functions as nutrient providers and the other in specialized roles such as defence or reproduction. This requires signalling systems to ensure harmonious development of multicellular structures. Here, we show that NADPH oxidases are specifically present in organisms that differentiate multicellular structures during their life cycle and are absent from unicellular life forms. The biochemical properties of these enzymes make them ideal candidates for a role in intercellular signalling.}, } @article {pmid12524337, year = {2002}, author = {Duncan, L and Bouckaert, K and Yeh, F and Kirk, DL}, title = {kangaroo, a mobile element from Volvox carteri, is a member of a newly recognized third class of retrotransposons.}, journal = {Genetics}, volume = {162}, number = {4}, pages = {1617-1630}, pmid = {12524337}, issn = {0016-6731}, mesh = {Amino Acid Sequence ; Base Sequence ; Chlorophyta/*genetics/growth & development ; DNA Nucleotidyltransferases/genetics ; DNA, Complementary/genetics ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Integrases/genetics ; Models, Genetic ; Molecular Sequence Data ; Recombinases ; Retroelements/*genetics ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Species Specificity ; }, abstract = {Retrotransposons play an important role in the evolution of genomic structure and function. Here we report on the characterization of a novel retrotransposon called kangaroo from the multicellular green alga, Volvox carteri. kangaroo elements are highly mobile and their expression is developmentally regulated. They probably integrate via double-stranded, closed-circle DNA intermediates through the action of an encoded recombinase related to the lambda-site-specific integrase. Phylogenetic analysis indicates that kangaroo elements are closely related to other unorthodox retrotransposons including PAT (from a nematode), DIRS-1 (from Dictyostelium), and DrDIRS1 (from zebrafish). PAT and kangaroo both contain split direct repeat (SDR) termini, and here we show that DIRS-1 and DrDIRS1 elements contain terminal features structurally related to SDRs. Thus, these mobile elements appear to define a third class of retrotransposons (the DIRS1 group) that are unified by common structural features, genes, and integration mechanisms, all of which differ from those of LTR and conventional non-LTR retrotransposons.}, } @article {pmid12520866, year = {2002}, author = {Wajcman, H and Kiger, L}, title = {[Hemoglobin, from microorganisms to man: a single structural motif, multiple functions].}, journal = {Comptes rendus biologies}, volume = {325}, number = {12}, pages = {1159-1174}, doi = {10.1016/s1631-0691(02)01537-8}, pmid = {12520866}, issn = {1631-0691}, mesh = {Animals ; Bacteria/chemistry ; Evolution, Molecular ; Globins ; Hemeproteins ; Hemoglobins/*chemistry/genetics/*physiology ; Humans ; Models, Molecular ; Oxygen/metabolism ; Phycocyanin ; Plants/chemistry ; Protein Folding ; }, abstract = {Haemoglobins from unicellular organisms, plants or animals, share a common structure, which results from the folding, around the heme group, of a polypeptide chain made from 6-8 helices. Nowadays, deciphering the genome of several species allows one to draw the evolutionary tree of this protein going back to 1800 millions of years, at a time when oxygen began to accumulate in the atmosphere. This permits to follow the evolution of the ancestral gene and of its product. It is likely that, only in complex multicellular species, transport and storage of oxygen became the main physiological function of this molecule. In addition, in unicellular organisms and small invertebrates, it is likely that the main function of this protein was to protect the organism from the toxic effect of O2, CO and NO*. The very high oxygen affinity of these molecules, leading them to act rather as a scavenger as an oxygen carrier, supports this hypothesis. Haemoglobins from microorganisms, which may probably be the closest vestiges to the ancestral molecules, are divided into three families. The first one is made from flavohaemoglobins, a group of chimerical proteins carrying a globin domain and an oxido-reduction FAD-dependant domain. The second corresponds to truncated haemoglobins, which are hexacoordinated with very high oxygen-affinity molecules, 20-40 residues shorter than classical haemoglobins. The third group is made from bacterial haemoglobins such as that of Vitreoscilla. Some specific structural arrangements in the region surrounding the heme are cause of their high oxygen affinity. In plants, two types of haemoglobins are present (non-symbiotic and symbiotic), that arose from duplication of an ancestral vegetal gene. Non-symbiotic haemoglobins, which are probably the oldest, are scarcely distributed within tissues having high energetic consumption. Conversely, symbiotic haemoglobins (also named leghaemoglobins) are present at a high concentration (mM) mostly in the rhizomes of legumes, where they are involved in nitrogen metabolism. In some species, haemoglobin was proposed to be an oxygen sensor bringing to the organism information to adjust metabolism or biosynthesis to the oxygen requirement. Elsewhere haemoglobin may act as final electron acceptors in oxido-reduction pathways. Evolution of haemoglobin in invertebrates followed a large variety of scenarios. Some surprising functions as sulphide acquisition in invertebrates living near hydrothermal vents, or a role in the phototrophism of worm need to be mentioned. In invertebrates, the size of haemoglobin varies from monomers to giant molecules associating up to 144 subunits, while in vertebrates it is always a tetramer. In some species, several haemoglobins, with completely different structure and function, may coexist. This demonstrates how hazardous may be to extrapolate the function of a protein from only structural data.}, } @article {pmid12511503, year = {2003}, author = {Christiansen, G and Fastner, J and Erhard, M and Börner, T and Dittmann, E}, title = {Microcystin biosynthesis in planktothrix: genes, evolution, and manipulation.}, journal = {Journal of bacteriology}, volume = {185}, number = {2}, pages = {564-572}, pmid = {12511503}, issn = {0021-9193}, mesh = {Amino Acid Sequence ; Bacterial Proteins/chemistry/*genetics/metabolism ; Cyanobacteria/*enzymology/genetics ; *Evolution, Molecular ; Gene Deletion ; Gene Expression Regulation, Bacterial ; Methyltransferases/chemistry/genetics/metabolism ; Microcystins ; Molecular Sequence Data ; Multigene Family ; Peptide Synthases/chemistry/*genetics/metabolism ; Peptides, Cyclic/*biosynthesis/chemistry/genetics ; *Transformation, Bacterial ; }, abstract = {Microcystins represent an extraordinarily large family of cyclic heptapeptide toxins that are nonribosomally synthesized by various cyanobacteria. Microcystins specifically inhibit the eukaryotic protein phosphatases 1 and 2A. Their outstanding variability makes them particularly useful for studies on the evolution of structure-function relationships in peptide synthetases and their genes. Analyses of microcystin synthetase genes provide valuable clues for the potential and limits of combinatorial biosynthesis. We have sequenced and analyzed 55.6 kb of the potential microcystin synthetase gene (mcy) cluster from the filamentous cyanobacterium Planktothrix agardhii CYA 126. The cluster contains genes for peptide synthetases (mcyABC), polyketide synthases (PKSs; mcyD), chimeric enzymes composed of peptide synthetase and PKS modules (mcyEG), a putative thioesterase (mcyT), a putative ABC transporter (mcyH), and a putative peptide-modifying enzyme (mcyJ). The gene content and arrangement and the sequence of specific domains in the gene products differ from those of the mcy cluster in Microcystis, a unicellular cyanobacterium. The data suggest an evolution of mcy clusters from, rather than to, genes for nodularin (a related pentapeptide) biosynthesis. Our data do not support the idea of horizontal gene transfer of complete mcy gene clusters between the genera. We have established a protocol for stable genetic transformation of Planktothrix, a genus that is characterized by multicellular filaments exhibiting continuous motility. Targeted mutation of mcyJ revealed its function as a gene coding for a O-methyltransferase. The mutant cells produce a novel microcystin variant exhibiting reduced inhibitory activity toward protein phosphatases.}, } @article {pmid12495507, year = {2002}, author = {Bulmer, MG and Parker, GA}, title = {The evolution of anisogamy: a game-theoretic approach.}, journal = {Proceedings. Biological sciences}, volume = {269}, number = {1507}, pages = {2381-2388}, pmid = {12495507}, issn = {0962-8452}, mesh = {Animals ; *Biological Evolution ; Female ; *Game Theory ; Germ Cells/*cytology/*physiology ; Male ; Models, Biological ; Ovum/physiology ; Reproduction ; Selection, Genetic ; Spermatozoa/physiology ; }, abstract = {A popular theory has proposed that anisogamy originated through disruptive selection acting on an ancestral isogamous population, though recent work has emphasized the importance of other factors in its evolution. We re-examine the disruptive selection theory, starting from an isogamous population with two mating types and taking into account the functional relationship, g(m), between the fitness of a gamete and its size, m, as well as the relationship, f(S), between the fitness of a zygote and its size, S. Evolutionary game theory is used to determine the existence and continuous stability of isogamous and anisogamous strategies for the two mating types under various models for the two functions g(m) and f(S). In the ancestral unicellular state, these two functions are likely to have been similar; this leads to isogamy whether they are sigmoidal or concave, though in the latter case allowance must be made for a minimal gamete size. The development of multicellularity may leave g(m) relatively unchanged while f(S) moves to the right, leading to the evolution of anisogamy. Thus, the disruptive selection theory provides a powerful explanation of the origin of anisogamy, though other selective forces may have been involved in the subsequent specialization of micro- and macrogametes.}, } @article {pmid12495504, year = {2002}, author = {Foster, KR and Fortunato, A and Strassmann, JE and Queller, DC}, title = {The costs and benefits of being a chimera.}, journal = {Proceedings. Biological sciences}, volume = {269}, number = {1507}, pages = {2357-2362}, pmid = {12495504}, issn = {0962-8452}, mesh = {Animals ; Biological Evolution ; Chimera/genetics/*physiology ; Dictyostelium/*genetics/growth & development/*physiology ; Light ; *Movement ; Reproduction ; Selection, Genetic ; }, abstract = {Most multicellular organisms are uniclonal. This is hypothesized to be because uniclonal organisms function better than chimeras (non-clonal organisms), owing to reduced levels of internal genetic conflict. We tested this idea using the social amoeba or slime mold Dictyostelium discoideum. When starving, the normally solitary amoebae aggregate to form a differentiated multicellular slug that migrates towards light and forms a fruiting body, facilitating the dispersal of spores. We added 10(7) amoebae to Petri plates containing 1, 2, 5 or 10 clones mixed together. We found an intrinsic cost to chimerism: chimeric slugs moved significantly less far than uniclonal slugs of the same size. However, in nature, joining with other clones to form a chimera should increase slug size, and larger slugs travel further. We incorporated this size effect into a second experiment by giving chimeras more cells than single clones (single clones had 10(6) cells, two-clone chimeras had 2 x 10(6) cells and so on). The uniclonal treatments then simulated a clone in a mixture that refuses to form chimeras. In this experiment, chimeras moved significantly further than the uniclonal slugs, in spite of the intrinsic cost. Thus, chimerism is costly, which may be why it evolves so seldom, but in D. discoideum the benefits of large size appear to compensate.}, } @article {pmid12492416, year = {2003}, author = {Schlichting, CD}, title = {Origins of differentiation via phenotypic plasticity.}, journal = {Evolution & development}, volume = {5}, number = {1}, pages = {98-105}, doi = {10.1046/j.1525-142x.2003.03015.x}, pmid = {12492416}, issn = {1520-541X}, mesh = {Animals ; Biological Evolution ; *Cell Differentiation ; Dictyosteliida ; Environment ; Eukaryota ; *Gene Expression Regulation, Developmental ; Genotype ; *Phenotype ; Phylogeny ; Signal Transduction ; }, abstract = {How cell types of multicellular organisms came to be differentiated is still an open issue. Here I offer a model that posits that the origins of some cell differentiation patterns were originally passive outcomes of environmental effects. As cells' contact with the external environment was diminished, their patterns of gene expression were altered, due to changes in concentrations of externally supplied substances. Later, as multicellular growth continued, the relationships of cell layers to each other shifted, producing concentration gradients of signaling molecules. These gradients emanated both from the external cell layer toward the inside and from internal cell layers to adjacent layers. In this scenario then, differentiation arose initially as a by-product of the changing patterns of gene expression and of the complex mixtures and changing concentrations of substances passing among layers. Subsequent selection would operate to stabilize the expression patterns in those cell layers whose phenotypes provide a fitness advantage to the organism.}, } @article {pmid12490925, year = {2002}, author = {Wolpert, L and Szathmáry, E}, title = {Multicellularity: evolution and the egg.}, journal = {Nature}, volume = {420}, number = {6917}, pages = {745}, doi = {10.1038/420745a}, pmid = {12490925}, issn = {0028-0836}, mesh = {Animals ; *Biological Evolution ; Cell Differentiation ; Female ; Hydra/cytology/genetics/physiology ; Male ; Mutation ; Ovum/*cytology/*physiology ; *Reproduction/genetics ; Reproduction, Asexual/genetics ; Spermatozoa/physiology ; }, } @article {pmid12490150, year = {2002}, author = {Gerbi, SA and Strezoska, Z and Waggener, JM}, title = {Initiation of DNA replication in multicellular eukaryotes.}, journal = {Journal of structural biology}, volume = {140}, number = {1-3}, pages = {17-30}, doi = {10.1016/s1047-8477(02)00538-5}, pmid = {12490150}, issn = {1047-8477}, support = {GM35929/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; Chromatin/chemistry ; DNA/*chemistry/metabolism/*physiology ; DNA-Binding Proteins ; Diptera ; Models, Biological ; Models, Genetic ; Origin Recognition Complex ; Saccharomycetales ; }, abstract = {Three questions central to understanding the initiation of DNA replication in eukaryotes are: (1) Does DNA synthesis begin at a defined place? (2) What determines replication initiation sites? (3) What regulates an origin to fire only once per cell cycle? A key player in this is the origin recognition complex (ORC), required for assembly of the pre-replication complex (pre-RC), that is converted later to the initiation complex (IC). In both yeast ARS1 and DNA puff II/9A of the metazoan fly Sciara, there is a defined start site of replication adjacent to an ORC-binding site. Although ORC has some inherent preference for certain DNA sequences, other factors may also modulate its binding to DNA. The preferred site where DNA synthesis starts at Sciara II/9A and the boundaries of the initiation zone change during development, when DNA puff amplification occurs. The position of the initiation zone may be influenced by the transcriptional machinery and/or chromatin structure. With regard to the third question, rereplication of the whole genome in yeast occurs when components of the pre-RC are stabilized by mutation. In contrast, a locus-specific amplification factor probably exists to account for site-specific DNA amplification in flies.}, } @article {pmid12486531, year = {2002}, author = {Shiba, K}, title = {Intron positions delineate the evolutionary path of a pervasively appended peptide in five human aminoacyl-tRNA synthetases.}, journal = {Journal of molecular evolution}, volume = {55}, number = {6}, pages = {727-733}, doi = {10.1007/s00239-002-2368-3}, pmid = {12486531}, issn = {0022-2844}, mesh = {Amino Acid Sequence ; Amino Acyl-tRNA Synthetases/chemistry/genetics/*metabolism ; *Evolution, Molecular ; *Introns ; Molecular Sequence Data ; Sequence Homology, Amino Acid ; }, abstract = {Recent progress in genome sequencing has revealed a correspondence between the evolution of multicellularity and the appending of new peptides onto age-old enzyme bodies. Indicative of the pervasive nature of these appended peptides, in some cases the same sequences have been appended to a number of different enzymes. By analyzing the positions of introns within one such roaming peptide, an approximately 50-amino acid motif appended to five human aminoacyl-tRNA synthetases, I have delineated its path in eukaryote evolution. The motif was first acquired as an N-terminal extension by histidyl- and glycyl-tRNA synthetases at a very early stage of eukaryote evolution. Later, but not less than 1200 million years ago, the motif spread from histidyl-tRNA synthetase to the C and N terminals of glutamyl- and prolyl-tRNA synthetase, respectively, and then spread further during the evolution of the Chordate lineage to the N terminal of tryptophanyl-tRNA synthetase. In similar fashion, the motif in glycyl-tRNA synthetase spread to the C terminal of methionyl-tRNA synthetase not later than 1000 million years ago.}, } @article {pmid12485687, year = {2002}, author = {Canty, EG and Kadler, KE}, title = {Collagen fibril biosynthesis in tendon: a review and recent insights.}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {133}, number = {4}, pages = {979-985}, doi = {10.1016/s1095-6433(02)00212-x}, pmid = {12485687}, issn = {1095-6433}, mesh = {Animals ; Extracellular Matrix/chemistry/metabolism ; Fibrillar Collagens/*biosynthesis/metabolism ; Procollagen/metabolism ; Tendons/chemistry/*metabolism ; }, abstract = {The development and evolution of multicellular animals relies on the ability of certain cell types to synthesise an extracellular matrix (ECM) comprising very long collagen fibrils that are arranged in very ordered 3-dimensional scaffolds. Tendon is a good example of a highly ordered ECM, in which tens of millions of collagen fibrils, each hundreds of microns long, are synthesised parallel to the tendon long axis. This review highlights recent discoveries showing that the assembly of collagen fibrils in tendon is hierarchical, and involves the formation of fairly short "collagen early fibrils" that are the fusion precursors of the very long fibrils that occur in mature tendon.}, } @article {pmid12468283, year = {2003}, author = {Williams, RJ and Fraústo Da Silva, JJ}, title = {Evolution was chemically constrained.}, journal = {Journal of theoretical biology}, volume = {220}, number = {3}, pages = {323-343}, doi = {10.1006/jtbi.2003.3152}, pmid = {12468283}, issn = {0022-5193}, mesh = {Animals ; Atmosphere/chemistry ; Cytoplasm/chemistry ; Earth, Planet ; Ecosystem ; Elements ; Eukaryotic Cells/chemistry ; *Evolution, Chemical ; Humans ; Prokaryotic Cells/chemistry ; Seawater/chemistry ; }, abstract = {The objective of this paper is to present a systems view of the major features of biological evolution based upon changes in internal chemistry and uses of cellular space, both of which it will be stated were dependent on the changing chemical environment. The account concerns the major developments from prokaryotes to eukaryotes, to multi-cellular organisms, to animals with nervous systems and a brain, and finally to human beings and their uses of chemical elements in space outside themselves. It will be stated that the changes were in an inevitable progression, and were not just due to blind chance, so that "random searching" by a coded system to give species had a fixed overall route. The chemical sequence is from a reducing to an ever-increasingly oxidizing environment, while organisms retained reduced chemicals. The process was furthered recently by human beings who have also increased the range of reduced products trapped on Earth in novel forms. All the developments are brought about from the nature of the chemicals which organisms accumulate using the environment and its changes. The relationship to the manner in which particular species (gene sequences) were coincidentally changed, the molecular view of evolution, is left for additional examination. There is a further issue in that the changes of the chemistry of the environment developed largely at equilibrium due to the relatively fast reactions there of the available inorganic chemicals. Inside cells, some of these same chemicals also came to equilibrium within compounds. All such equilibria reduced the variance (degrees of freedom) of the total environmental/biological system and its possible development. However, the more sophisticated organic chemistry, almost totally inside cells until humans evolved, is kinetically controlled and limited by the demands of cellular reduction necessary to produce essential chemicals and by the availability of certain elements and energy. Hence the variability of reductive cellular organic chemistry and its limitations in cells have to be considered separately. While as a whole they drive the oxidation of the environment, they also allow speciation within the major changes of organisms. Human beings have introduced recently new, virtually irreversible, inorganic and organic chemistry in the environment, much of it new modes of irreversible storage of reduced chemicals, and this is, we state, the last possible step of chemical evolution. We must attempt to evaluate its effect on organisms generally. It must be clear that all the changes and the original life forms are dependent upon energy as well as material capture and flow. We shall have to consider in which forms energy was available over the period of evolution, how it was usefully transformed, and the ways in which its sources changed.}, } @article {pmid12467242, year = {2002}, author = {Fluhr, R and Kaplan-Levy, RN}, title = {Plant disease resistance: commonality and novelty in multicellular innate immunity.}, journal = {Current topics in microbiology and immunology}, volume = {270}, number = {}, pages = {23-46}, doi = {10.1007/978-3-642-59430-4_2}, pmid = {12467242}, issn = {0070-217X}, mesh = {Amino Acid Sequence ; Animals ; Edible Grain ; Environment ; Evolution, Molecular ; Humans ; Immunity, Innate ; Molecular Sequence Data ; Nuclear Proteins/genetics ; Phylogeny ; Plant Diseases/*genetics ; Plant Proteins/genetics ; Plants/genetics/*immunology ; Protein Serine-Threonine Kinases ; }, abstract = {Pathogen avirulence genes encode for effector molecules that play a crucial role in the process of pathogen colonization of plant tissue. Successful host defense requires rapid and efficient detection of the pathogen avirulence factors. In the last few years, much progress has been made in delineating the plant molecular sentinels that participate in pathogen identification. Because this ability is genetic information that is 'hard-wired' into the genome, it is called 'innate immunity' and it draws its origins from a phylogenetically ancient form of immunity common to plants and animals. Conservation is shown in many of the functional molecular motifs of innate genes such as the Toll/interleukin 1 receptor domains, nucleotide binding domains and structures that contain leucine rich repeats. Novel plant molecular surveillance domains also include pathogen pattern recognition by coiled-coil domains and specialized kinases. The rapid evolution of plant innate immunity genes is readily detected in their sequence polymorphism, by their massive amplification and appearance in the genome in a clustered organization. By comparative biology of highly diverged innate immunity systems we can enhance our appreciation of the truly basic forces that have shaped its evolution in mutlicellular organisms.}, } @article {pmid12466527, year = {2002}, author = {Pandey, R and Müller, A and Napoli, CA and Selinger, DA and Pikaard, CS and Richards, EJ and Bender, J and Mount, DW and Jorgensen, RA}, title = {Analysis of histone acetyltransferase and histone deacetylase families of Arabidopsis thaliana suggests functional diversification of chromatin modification among multicellular eukaryotes.}, journal = {Nucleic acids research}, volume = {30}, number = {23}, pages = {5036-5055}, pmid = {12466527}, issn = {1362-4962}, mesh = {Acetyltransferases/classification/*genetics/physiology ; Alternative Splicing ; Amino Acid Sequence ; Animals ; Arabidopsis/*enzymology/*genetics ; CREB-Binding Protein ; Caenorhabditis elegans/enzymology/genetics ; Chromatin/metabolism ; Drosophila Proteins ; Drosophila melanogaster/enzymology/genetics ; Fungal Proteins/genetics ; Genome, Plant ; Histone Acetyltransferases ; Histone Deacetylase 1 ; Histone Deacetylases/classification/*genetics/physiology ; Molecular Sequence Data ; Nuclear Proteins/genetics ; *Phylogeny ; Protein Structure, Tertiary ; *Repressor Proteins ; Saccharomyces cerevisiae/enzymology/genetics ; Saccharomyces cerevisiae Proteins/classification/*genetics/physiology ; Schizosaccharomyces/enzymology/genetics ; Sequence Homology, Amino Acid ; Sirtuins/genetics ; Trans-Activators/genetics ; *Transcription Factors ; Transcription Factors, TFII/genetics ; }, abstract = {Sequence similarity and profile searching tools were used to analyze the genome sequences of Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans and Drosophila melanogaster for genes encoding three families of histone deacetylase (HDAC) proteins and three families of histone acetyltransferase (HAT) proteins. Plants, animals and fungi were found to have a single member of each of three subfamilies of the GNAT family of HATs, suggesting conservation of these functions. However, major differences were found with respect to sizes of gene families and multi-domain protein structures within other families of HATs and HDACs, indicating substantial evolutionary diversification. Phylogenetic analysis identified a new class of HDACs within the RPD3/HDA1 family that is represented only in plants and animals. A similar analysis of the plant-specific HD2 family of HDACs suggests a duplication event early in dicot evolution, followed by further diversification in the lineage leading to Arabidopsis. Of three major classes of SIR2-type HDACs that are found in animals, fungi have representatives only in one class, whereas plants have representatives only in the other two. Plants possess five CREB-binding protein (CBP)-type HATs compared with one to two in animals and none in fungi. Domain and phylogenetic analyses of the CBP family proteins showed that this family has evolved three distinct types of CBPs in plants. The domain architecture of CBP and TAF(II)250 families of HATs show significant differences between plants and animals, most notably with respect to bromodomain occurrence and their number. Bromodomain-containing proteins in Arabidopsis differ strikingly from animal bromodomain proteins with respect to the numbers of bromodomains and the other types of domains that are present. The substantial diversification of HATs and HDACs that has occurred since the divergence of plants, animals and fungi suggests a surprising degree of evolutionary plasticity and functional diversification in these core chromatin components.}, } @article {pmid12464568, year = {2002}, author = {Forsdyke, DR and Madill, CA and Smith, SD}, title = {Immunity as a function of the unicellular state: implications of emerging genomic data.}, journal = {Trends in immunology}, volume = {23}, number = {12}, pages = {575-579}, doi = {10.1016/s1471-4906(02)02329-3}, pmid = {12464568}, issn = {1471-4906}, mesh = {Alu Elements ; DNA, Intergenic/genetics/immunology ; Evolution, Molecular ; Genome ; Humans ; Immunity/*genetics ; Polymorphism, Genetic ; Proteins/genetics/immunology ; RNA, Double-Stranded/genetics/immunology ; }, abstract = {Instead of being greeted as supporting the growing corpus of immunological theory, recent advances in the bioinformatic analysis of genomes have often surprised the discoverers and failed to attract the attention of immunologists. In fact, the view that multicellular immune systems are adaptations of already highly evolved unicellular immune systems that are capable of self/not-self discrimination can assist our comprehension of phenomena, such as 'junk' DNA, genetic polymorphism and the ubiquity of repetitive elements. For instance, the 'hidden transcriptome', revealed by run-on transcription of genes or repetitive elements, contains a diverse repertoire of RNA 'immune receptors' with the potential to form double-stranded RNA with viral RNA 'antigens', thus triggering intracellular alarms.}, } @article {pmid12459919, year = {2002}, author = {Herold, M and Cikala, M and MacWilliams, H and David, CN and Böttger, A}, title = {Cloning and characterisation of PKB and PRK homologs from Hydra and the evolution of the protein kinase family.}, journal = {Development genes and evolution}, volume = {212}, number = {11}, pages = {513-519}, doi = {10.1007/s00427-002-0267-7}, pmid = {12459919}, issn = {0949-944X}, mesh = {Amino Acid Sequence ; Animals ; Binding Sites ; Cloning, Molecular ; Escherichia coli/enzymology/genetics ; *Evolution, Molecular ; Hydra/classification/*enzymology/genetics ; Molecular Sequence Data ; Molecular Weight ; Phylogeny ; Protein Serine-Threonine Kinases/chemistry/*genetics/metabolism ; Proto-Oncogene Proteins/*genetics/metabolism ; Proto-Oncogene Proteins c-akt ; Recombinant Proteins/chemistry/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {Two new serine/threonine protein kinases have been cloned from Hydra cDNA. The first of these kinases belongs to the PKB/Akt family. It is expressed ubiquitously in Hydra at a relatively low level but is upregulated during head regeneration. The second kinase is a member of the PRK/PKN family. It is ubiquitously expressed in Hydra tissue, albeit at a higher level than PKB. Construction of a phylogenetic tree including the Hydra PRK and PKB kinases and two PKC homologs previously cloned by Hassel and comparing them with members of the PKC, PKB and PRK families from porifera, Dictyostelium,yeast, Drosophila, Caenorhabditis and humans provide support for a simple model for the evolution of these kinase families. An ancestral precursor which contained a pleckstrin homology domain in its N-terminus and a C-terminal kinase domain gave rise to PKB in Dictyostelium. From this ancestor the PKB/PRK and PKC families evolved. The pleckstrin homology domain was lost in the PKC and PRK families and kept in the PKB family. PKB homologs have now been found in a variety of multicellular animals with Hydra being the phylogenetically earliest representative. Members of the PRK/PKC family, on the other hand, are also present in fungi. The precursor for these kinases must have contained N-terminal regulatory domains that were retained in fungal PRKs but subsequently partitioned between kinases of the PKC and PRK groups in metazoans.}, } @article {pmid12459450, year = {2002}, author = {Holmquist, GP}, title = {Cell-selfish modes of evolution and mutations directed after transcriptional bypass.}, journal = {Mutation research}, volume = {510}, number = {1-2}, pages = {141-152}, doi = {10.1016/s0027-5107(02)00259-2}, pmid = {12459450}, issn = {0027-5107}, mesh = {Alleles ; Animals ; DNA/genetics/metabolism ; *DNA Damage ; DNA-Directed RNA Polymerases/metabolism ; *Evolution, Molecular ; Models, Genetic ; Mutagenesis ; *Mutation ; Transcription, Genetic ; }, abstract = {During transcription, prokaryotic and eukaryotic RNA polymerases bypass and misread (transcriptional mutagenesis) several classes of DNA lesions. For example, misreading of 8-OH-dG generates mRNAs containing G to T transversions. After translation, if the mutant protein briefly allowed the cell a growth-DNA replication advantage, then precocious DNA replication would bypass that unrepaired 8-OH-dG and misinsert dA opposite the directing DNA lesion with a higher probability than would be experienced for 8-OH-G lesions at other positions in otherwise identical neighboring cells. Such retromutations would have been tested for their imparted growth advantage as mRNA before they became heritable DNA mutations. The logical properties of a mode of evolution that utilizes directed-retromutagenesis were compared one by one with those of the standard neo-Darwinian mode. The retromutagenesis mode, while minimizing mutational load, is cell-selfish; fitness is for an immediate growth advantage rather than future reproductive potential. In prokaryotes, an evolutionary mode that involves standard Darwinian fitness testing of novel alleles in the genetic background of origin followed by clonal expansion also favors cell-selfish allele combinations when linkage disequilibrium is practiced. For metazoa and plants to have evolved organized tissues, cell-selfish modes of evolution represent systems-poisons that must be totally suppressed. The feedback loops that allow evolution to be cell-serving in prokaryotes are actively blocked in eukaryotes by traits that restrict fitness to future reproductive potential. These traits include (i) delay of fitness testing until after the mutation is made permanently heritable, (ii) diploidy to further delay fitness testing, (iii) segregation of somatic lines from germ lines, (iv) testing of novel alleles against randomized allele combinations constructed by obligate sex, and (v) obligate genetic death to insure that that the most basic systems unit of selfish allele combinatorial uniqueness is the species instead of the cell. The analyses indicate that modes of evolution in addition to our neo-Darwinian one could have existed utilizing known molecular mechanisms. The evolution of multicellularity was as much the discarding of old cell-selfish habits as the acquisition of new altruistic ones.}, } @article {pmid12456301, year = {2003}, author = {Hortsch, M}, title = {Neural cell adhesion molecules--brain glue and much more!.}, journal = {Frontiers in bioscience : a journal and virtual library}, volume = {8}, number = {}, pages = {d357-9}, doi = {10.2741/1006}, pmid = {12456301}, issn = {1093-9946}, mesh = {Animals ; Brain/*physiology ; Humans ; Neural Cell Adhesion Molecules/*physiology ; }, abstract = {The formation of stable cell contacts is of pivotal importance for every metazoan life form. It is therefore not surprising that adhesive molecules appeared early during the evolution of multicellular organisms. The pioneering work of Johannes Holtfreter and others indicated that adhesive molecules, which reside in the plasma membrane on the surface of most cells, are not only important for establishing general cell adhesion and cellular contacts, but also convey a specific tissue and cellular identity to their host cells (1). Over the last few decades a large number of cell adhesion molecules (CAMs) have been identified and further characterized, and we have learned that the expression of these proteins is highly choreographed in terms of timing and cell identity.}, } @article {pmid12452280, year = {2002}, author = {Andrianopoulos, A}, title = {Control of morphogenesis in the human fungal pathogen Penicillium marneffei.}, journal = {International journal of medical microbiology : IJMM}, volume = {292}, number = {5-6}, pages = {331-347}, doi = {10.1078/1438-4221-00217}, pmid = {12452280}, issn = {1438-4221}, mesh = {Cell Division/genetics ; Gene Expression Regulation, Fungal ; Humans ; Hyphae/genetics/*growth & development ; Penicillium/genetics/*growth & development ; Phylogeny ; Signal Transduction/genetics ; Spores, Fungal/genetics/*growth & development ; Yeasts/genetics/*growth & development ; }, abstract = {Fungal pathogens are an increasing threat to human health due to the increasing population of immunocompromised individuals and the increased incidence of treatment-derived infections. Penicillium marneffei is an emerging fungal pathogen endemic to South-east Asia, where it is AIDS defining. Like many other fungal pathogens, P. marneffei is capable of alternating between a filamentous and a yeast growth form, known as dimorphic switching, in response to environmental stimuli. P. marneffei grows in the filamentous form at 25 degrees C and in the yeast form at 37 degrees C. During filamentous growth and in response to environmental cues, P. marneffei undergoes asexual development to form complex multicellular structures from which the infectious agents, the conidia, are produced. At 37 degrees C, P. marneffei undergoes the dimorphic switching program to produce the pathogenic yeast cells. These yeast cells are found intracellularly in the mononuclear phagocyte system of the host and divide by fission, in contrast to the budding mode of division exhibited by most other fungal pathogens. In addition, P. marneffei is evolutionarily distinct from most other dimorphic fungal pathogens and is the only known Penicillium species which exhibits dimorphic growth. The unique evolutionary history of P. marneffei and the rapidly increasing incidence of infection, coupled with the presence of both complex asexual development and dimorphic switching programs in one organism, makes this system a valuable one for the study of morphogenesis and pathogenicity. Recent development of molecular genetic techniques for P. marneffei, including DNA-mediated transformation, have greatly facilitated the study of these two important morphogenetic programs, asexual development and dimorphic switching, and we are beginning to uncover important determinants which control these events. Understand these programs is providing insights into the biology of P. marneffei and its pathogenic capacity.}, } @article {pmid12448714, year = {2002}, author = {Velicer, GJ and Stredwick, KL}, title = {Experimental social evolution with Myxococcus xanthus.}, journal = {Antonie van Leeuwenhoek}, volume = {81}, number = {1-4}, pages = {155-164}, doi = {10.1023/a:1020546130033}, pmid = {12448714}, issn = {0003-6072}, mesh = {*Biological Evolution ; *Movement ; Myxococcus xanthus/genetics/growth & development/*physiology ; Spores, Bacterial/physiology ; }, abstract = {Genetically-based social behaviors are subject to evolutionary change in response to natural selection. Numerous microbial systems provide not only the opportunity to understand the genetic mechanisms underlying specific social interactions, but also to observe evolutionary changes in sociality over short time periods. Here we summarize experiments in which behaviors of the social bacterium Myxococcus xanthus changed extensively during evolutionary adaptation to two relatively asocial laboratory environments. M. xanthus moves cooperatively, exhibits cooperative multicellular development upon starvation and also appears to prey cooperatively on other bacteria. Replicate populations of M. xanthus were evolved in both structured (agar plate) and unstructured (liquid) environments that contained abundant resources. The importance of social cooperation for evolutionary fitness in these habitats was limited by the absence of positive selection for starvation-induced spore production or predatory efficiency. Evolved populations showed major losses in all measured categories of social proficiency- motility, predation, fruiting ability, and sporulation. Moreover, several evolved genotypes were observed to exploit the social behavior of their ancestral parent when mixed together during the developmental process. These experiments that resulted in both socially defective and socially exploitative genotypes demonstrate the power of laboratory selection experiments for studying social evolution at the microbial level. Results from additional selection experiments that place positive selection pressure on social phenotypes can be integrated with direct study of natural populations to increase our understanding of principles that underlie the evolution of microbial social behavior.}, } @article {pmid12444920, year = {2003}, author = {Kennelly, PJ}, title = {Archaeal protein kinases and protein phosphatases: insights from genomics and biochemistry.}, journal = {The Biochemical journal}, volume = {370}, number = {Pt 2}, pages = {373-389}, pmid = {12444920}, issn = {0264-6021}, mesh = {Archaea/chemistry/*enzymology/genetics ; Archaeal Proteins/chemistry/*genetics/metabolism ; Enzyme Activation/genetics/physiology ; Histidine Kinase ; Phosphoprotein Phosphatases/chemistry/*genetics/metabolism ; Phosphorus Radioisotopes/metabolism ; Phylogeny ; Protein Kinases/chemistry/*genetics/metabolism ; }, abstract = {Protein phosphorylation/dephosphorylation has long been considered a recent addition to Nature's regulatory arsenal. Early studies indicated that this molecular regulatory mechanism existed only in higher eukaryotes, suggesting that protein phosphorylation/dephosphorylation had emerged to meet the particular signal-transduction requirements of multicellular organisms. Although it has since become apparent that simple eukaryotes and even bacteria are sites of protein phosphorylation/dephosphorylation, the perception widely persists that this molecular regulatory mechanism emerged late in evolution, i.e. after the divergence of the contemporary phylogenetic domains. Only highly developed cells, it was reasoned, could afford the high 'overhead' costs inherent in the acquisition of dedicated protein kinases and protein phosphatases. The advent of genome sequencing has provided an opportunity to exploit Nature's phylogenetic diversity as a vehicle for critically examining this hypothesis. In tracing the origins and evolution of protein phosphorylation/dephosphorylation, the members of the Archaea, the so-called 'third domain of life', will play a critical role. Whereas several studies have demonstrated that archaeal proteins are subject to modification by covalent phosphorylation, relatively little is known concerning the identities of the proteins affected, the impact on their functional properties, or the enzymes that catalyse these events. However, examination of several archaeal genomes has revealed the widespread presence of several ostensibly 'eukaryotic' and 'bacterial' protein kinase and protein phosphatase paradigms. Similar findings of 'phylogenetic trespass' in members of the Eucarya (eukaryotes) and the Bacteria suggest that this versatile molecular regulatory mechanism emerged at an unexpectedly early point in development of 'life as we know it'.}, } @article {pmid12443689, year = {2002}, author = {Yatsuda, AP and Eysker, M and Vieira-Bressan, MC and De Vries, E}, title = {A family of activation associated secreted protein (ASP) homologues of Cooperia punctata.}, journal = {Research in veterinary science}, volume = {73}, number = {3}, pages = {297-306}, doi = {10.1016/s0034-5288(02)00125-x}, pmid = {12443689}, issn = {0034-5288}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Western ; Cattle ; Cattle Diseases/*parasitology ; DNA, Complementary/genetics ; Enzyme-Linked Immunosorbent Assay ; Escherichia coli/genetics ; Helminth Proteins/*genetics/metabolism/physiology ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; RNA, Helminth/genetics/metabolism ; Random Amplified Polymorphic DNA Technique ; Recombinant Proteins/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Nucleic Acid ; Trichostrongyloidea/*genetics/metabolism/physiology ; Trichostrongyloidiasis/parasitology/*veterinary ; }, abstract = {Activation-associated secreted proteins (ASP) of nematodes have been studied as potential vaccine components. In this study we report the cloning and analysis of cDNA and genomic sequences of Cooperia punctata and establish the presence of two 75% identical ASP-1 genes in C. punctata. Additional C. punctata ASP paralogues were shown to be present. Analysis of PCR products amplified from genomic DNA from a pool of worms revealed extensive sequence diversity within this family of proteins, reflecting the presence of different ASP paralogues in a single worm as well as extensive polymorphisms between different worms. ASP proteins contain a conserved region called the sperm-coating protein (SCP) domain of unknown function, which is present as a single copy in proteins from yeast and a wide range of multi-cellular organisms. Only in three nematodes has a protein composed of duplicated SCP-domains been identified. C. punctata is the first organism in which at least two such genes are found. Database searches identified similarity of the C-terminal cysteine-rich domain of ASP proteins to a nematode metallothionein motif. Cp-asp-1b was expressed in Escherichia coli and both the N-terminal and C-terminal domain were shown to be recognized by sera of C. punctata infected bovines. The description of the asp gene family of C. punctata provides the basis for more detailed studies into the extent of variation and immunological recognition of this family that may assist in rational vaccine design.}, } @article {pmid12441685, year = {2001}, author = {Wang, Z and Bhattacharya, N and Weaver, M and Petersen, K and Meyer, M and Gapter, L and Magnuson, NS}, title = {Pim-1: a serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis.}, journal = {Journal of veterinary science}, volume = {2}, number = {3}, pages = {167-179}, pmid = {12441685}, issn = {1229-845X}, mesh = {Animals ; Apoptosis/*physiology ; Cell Differentiation/physiology ; Cell Division/*physiology ; *Cell Transformation, Neoplastic ; Gene Expression Regulation, Enzymologic ; Humans ; Lymphoma/etiology ; Mice ; Protein Serine-Threonine Kinases/genetics/*physiology ; Proto-Oncogene Proteins/genetics/*physiology ; Proto-Oncogene Proteins c-pim-1 ; Signal Transduction ; }, abstract = {Pim-1 belongs to a family of serine/threonine protein kinases that are highly conserved through evolution in multicellular organisms. Originally identified from moloney murine leukemia virus (MuLV)-induced T-cell lymphomas in mice, Pim-1 kinase is involved in the control of cell growth, differentiation and apoptosis. Expression of Pim-1 kinase can be stimulated by a variety of growth factors and regulated at four different levels: transcriptional, post-transcriptional, translational and post-translational. Several signal transduction pathways may be associated with the regulation of Pim-1's expression; accumulating data support that the expression of Pim-1 protein is mediated through activation of JAK/STATs. Recent studies of Pim family kinases indicate that Pim-1 kinase plays important roles outside of the hematopoietic system as well.}, } @article {pmid12431370, year = {2002}, author = {Gibson-Brown, JJ}, title = {T-box time in England.}, journal = {Developmental cell}, volume = {3}, number = {5}, pages = {625-630}, doi = {10.1016/s1534-5807(02)00330-1}, pmid = {12431370}, issn = {1534-5807}, mesh = {Animals ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Humans ; Mice ; T-Box Domain Proteins/*genetics/*physiology ; United Kingdom ; }, abstract = {T-box genes encode DNA binding transcription factors known to regulate a wide variety of developmental processes during embryogenesis and are present in the genomes of all multicellular animals. Indeed, alongside other more familiar families of developmental regulators such as Hox, Sox, and Pax, T-box genes constitute one of the fundamental components of the universal metazoan "toolkit" of developmental genes. A recent meeting in Nottingham, England celebrated the first decade of T-box gene research and demonstrated just how much has been learned in the relatively short time since their discovery.}, } @article {pmid12426481, year = {2002}, author = {Okuyama, M and Saito, Y and Ogawa, M and Takeuchi, A and Jing, Z and Naganuma, T and Hirose, E}, title = {Morphological studies on the bathyal ascidian, Megalodicopia hians Oka 1918 (Octacnemidae, Phlebobranchia), with remarks on feeding and tunic morphology.}, journal = {Zoological science}, volume = {19}, number = {10}, pages = {1181-1189}, doi = {10.2108/zsj.19.1181}, pmid = {12426481}, issn = {0289-0003}, mesh = {Animals ; Environment ; *Feeding Behavior ; Gonads/anatomy & histology ; Integumentary System/anatomy & histology/microbiology ; Intestines/anatomy & histology ; Japan ; Oceans and Seas ; Phylogeny ; Species Specificity ; Urochordata/*anatomy & histology/classification/*physiology ; }, abstract = {Megalodicopia hians Oka is a solitary ascidian belonging to the family Octacnemidae inhabiting the bathyal /abyssal zone as well as other octacnemid ascidians. The phylogenetic relationship of octacnemids is open to argument because of its extraordinary morphological features due to habitat adaptation, e.g., a pharynx lacking ciliated stigmata. Aggregations of M. hians were discovered by the manned submersible Shinkai 2000 in the bathyal seafloor of Toyama Bay, Japan Sea, in 2000; this was the first in situ observation of M. hians in the Japanese coastal waters. In 2001, a total of 36 M. hians specimens were collected from the bay (592 to approximately 978 m deep). In situ observation indicated that M. hians usually opens its large oral apertures to engulf the drifting food particles in the water current. Microscopical observation of the gut contents also showed that M. hians is a non selective macrophagous feeding on small crustaceans, diatoms, detritus, and so on. Along with the position of the intestinal loop and gonad, the morphological characteristics of the tunic (integument of ascidians) suggest that M. hians is closely related to Cionidae and/or Corellidae. Some symbiotic/parasitic organisms were occasionally found in the tunic, including rod-shaped bacteria, fungi-like multicellular structure, and spawns of unknown animals.}, } @article {pmid12421750, year = {2002}, author = {Kaessmann, H and Zöllner, S and Nekrutenko, A and Li, WH}, title = {Signatures of domain shuffling in the human genome.}, journal = {Genome research}, volume = {12}, number = {11}, pages = {1642-1650}, pmid = {12421750}, issn = {1088-9051}, support = {R01 GM065499/GM/NIGMS NIH HHS/United States ; GM30998/GM/NIGMS NIH HHS/United States ; GM65499/GM/NIGMS NIH HHS/United States ; R37 GM030998/GM/NIGMS NIH HHS/United States ; R01 GM030998/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans Proteins/chemistry/classification/genetics ; Databases, Protein/statistics & numerical data ; Evolution, Molecular ; Exons/genetics ; *Genome, Human ; Humans ; Introns/genetics ; Protein Structure, Tertiary/genetics ; Proteome/chemistry/classification/genetics ; }, abstract = {To elucidate the role of exon shuffling in shaping the complexity of the human genome/proteome, we have systematically analyzed intron phase distributions in the coding sequence of human protein domains. We found that introns at the boundaries of domains show high excess of symmetrical phase combinations (i.e., 0-0, 1-1, and 2-2), whereas nonboundary introns show no excess symmetry. This suggests that exon shuffling has primarily involved rearrangement of structural and functional domains as a whole. Furthermore, we found that domains flanked by phase 1 introns have dramatically expanded in the human genome due to domain shuffling and that 1-1 symmetrical domains and domain families are nonrandomly distributed with respect to their age. The predominance and extracellular location of 1-1 symmetrical domains among domains specific to metazoans suggests that they are associated with the rise of multicellularity. On the other hand, 0-0 symmetrical domains tend to be over-represented among ancient protein domains that are shared between the eukaryotic and prokaryotic kingdoms, which is compatible with the suggestion of primordial domain shuffling in the progenote. To see whether the human data reflect general genomic patterns of metazoans, similar analyses were done for the nematode Caenorhabditis elegans. Although the C. elegans data generally concur with the human patterns, we identified fewer intron-bounded domains in this organism, consistent with the lower complexity of C. elegans genes. [The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: Z. Gu and R. Stevens.]}, } @article {pmid12421749, year = {2002}, author = {Müller, A and MacCallum, RM and Sternberg, MJ}, title = {Structural characterization of the human proteome.}, journal = {Genome research}, volume = {12}, number = {11}, pages = {1625-1641}, pmid = {12421749}, issn = {1088-9051}, mesh = {Algorithms ; Animals ; Archaeal Proteins/chemistry/classification/genetics/physiology ; Bacterial Proteins/chemistry/classification/genetics/physiology ; Caenorhabditis elegans Proteins/chemistry/classification/genetics/physiology ; Databases, Genetic/statistics & numerical data ; Drosophila Proteins/chemistry/classification/genetics/physiology ; Escherichia coli Proteins/chemistry/classification/genetics/physiology ; Gene Duplication ; Genetic Diseases, Inborn/genetics ; Humans ; Markov Chains ; Membrane Proteins/chemistry/classification/genetics/physiology ; Online Systems/statistics & numerical data ; Phylogeny ; Protein Structure, Quaternary/genetics/physiology ; Proteome/*chemistry/classification/physiology ; Saccharomyces cerevisiae Proteins/chemistry/classification/genetics/physiology ; }, abstract = {This paper reports an analysis of the encoded proteins (the proteome) of the genomes of human, fly, worm, yeast, and representatives of bacteria and archaea in terms of the three-dimensional structures of their globular domains together with a general sequence-based study. We show that 39% of the human proteome can be assigned to known structures. We estimate that for 77% of the proteome, there is some functional annotation, but only 26% of the proteome can be assigned to standard sequence motifs that characterize function. Of the human protein sequences, 13% are transmembrane proteins, but only 3% of the residues in the proteome form membrane-spanning regions. There are substantial differences in the composition of globular domains of transmembrane proteins between the proteomes we have analyzed. Commonly occurring structural superfamilies are identified within the proteome. The frequencies of these superfamilies enable us to estimate that 98% of the human proteome evolved by domain duplication, with four of the 10 most duplicated superfamilies specific for multicellular organisms. The zinc-finger superfamily is massively duplicated in human compared to fly and worm, and occurrence of domains in repeats is more common in metazoa than in single cellular organisms. Structural superfamilies over- and underrepresented in human disease genes have been identified. Data and results can be downloaded and analyzed via web-based applications at http://www.sbg.bio.ic.ac.uk.}, } @article {pmid12415314, year = {2002}, author = {Hedges, SB}, title = {The origin and evolution of model organisms.}, journal = {Nature reviews. Genetics}, volume = {3}, number = {11}, pages = {838-849}, doi = {10.1038/nrg929}, pmid = {12415314}, issn = {1471-0056}, mesh = {Animals ; Archaea/genetics ; Bacteria/genetics ; *Biological Evolution ; Chronology as Topic ; Eukaryota/genetics ; Fungi/genetics ; Humans ; *Models, Biological ; *Phylogeny ; Plants/genetics ; }, abstract = {The phylogeny and timescale of life are becoming better understood as the analysis of genomic data from model organisms continues to grow. As a result, discoveries are being made about the early history of life and the origin and development of complex multicellular life. This emerging comparative framework and the emphasis on historical patterns is helping to bridge barriers among organism-based research communities.}, } @article {pmid12411597, year = {2002}, author = {Irving, JA and Steenbakkers, PJ and Lesk, AM and Op den Camp, HJ and Pike, RN and Whisstock, JC}, title = {Serpins in prokaryotes.}, journal = {Molecular biology and evolution}, volume = {19}, number = {11}, pages = {1881-1890}, doi = {10.1093/oxfordjournals.molbev.a004012}, pmid = {12411597}, issn = {0737-4038}, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Humans ; Molecular Sequence Data ; Phylogeny ; Prokaryotic Cells/*chemistry ; Protein Conformation ; Sequence Homology, Amino Acid ; Serpins/*chemistry/genetics ; Species Specificity ; Structure-Activity Relationship ; }, abstract = {Members of the serpin (serine proteinase inhibitor) superfamily have been identified in higher multicellular eukaryotes (plants and animals) and viruses but not in bacteria, archaea, or fungi. Thus, the ancestral serpin and the origin of the serpin inhibitory mechanism remain obscure. In this study we characterize 12 serpin-like sequences in the genomes of prokaryotic organisms, extending this protein family to all major branches of life. Notably, these organisms live in dramatically different environments and some are evolutionarily distantly related. A sequence-based analysis suggests that all 12 serpins are inhibitory. Despite considerable sequence divergence between the proteins, in four of the 12 sequences the region of the serpin that determines proteinase specificity is highly conserved, indicating that these inhibitors are likely to share a common target. Inhibitory serpins are typically prone to polymerization upon heating; thus, the existence of serpins in the moderate thermophilic bacterium Thermobifida fusca, the thermophilic bacterium Thermoanaerobacter tengcongensis, and the hyperthermophilic archaeon Pyrobaculum aerophilum is of particular interest. Using molecular modeling, we predict the means by which heat stability in the latter protein may be achieved without compromising inhibitory activity.}, } @article {pmid12401173, year = {2002}, author = {Lang, BF and O'Kelly, C and Nerad, T and Gray, MW and Burger, G}, title = {The closest unicellular relatives of animals.}, journal = {Current biology : CB}, volume = {12}, number = {20}, pages = {1773-1778}, doi = {10.1016/s0960-9822(02)01187-9}, pmid = {12401173}, issn = {0960-9822}, mesh = {Animals ; Biological Evolution ; DNA, Mitochondrial/genetics ; Eukaryota/*classification ; Fungi/*classification ; Molecular Sequence Data ; *Phylogeny ; Plants/*classification ; }, abstract = {Molecular phylogenies support a common ancestry between animals (Metazoa) and Fungi, but the evolutionary descent of the Metazoa from single-celled eukaryotes (protists) and the nature and taxonomic affiliation of these ancestral protists remain elusive. We addressed this question by sequencing complete mitochondrial genomes from taxonomically diverse protists to generate a large body of molecular data for phylogenetic analyses. Trees inferred from multiple concatenated mitochondrial protein sequences demonstrate that animals are specifically affiliated with two morphologically dissimilar unicellular protist taxa: Monosiga brevicollis (Choanoflagellata), a flagellate, and Amoebidium parasiticum (Ichthyosporea), a fungus-like organism. Statistical evaluation of competing evolutionary hypotheses confirms beyond a doubt that Choanoflagellata and multicellular animals share a close sister group relationship, originally proposed more than a century ago on morphological grounds. For the first time, our trees convincingly resolve the currently controversial phylogenetic position of the Ichthyosporea, which the trees place basal to Choanoflagellata and Metazoa but after the divergence of Fungi. Considering these results, we propose the new taxonomic group Holozoa, comprising Ichthyosporea, Choanoflagellata, and Metazoa. Our findings provide insight into the nature of the animal ancestor and have broad implications for our understanding of the evolutionary transition from unicellular protists to multicellular animals.}, } @article {pmid12392970, year = {2002}, author = {Dusenbery, DB}, title = {Ecological models explaining the success of distinctive sperm and eggs (oogamy).}, journal = {Journal of theoretical biology}, volume = {219}, number = {1}, pages = {1-7}, pmid = {12392970}, issn = {0022-5193}, mesh = {Animals ; Cell Size ; *Ecology ; Female ; Male ; Models, Biological ; Oocytes/*cytology ; Pheromones/physiology ; *Selection, Genetic ; Sperm Motility/physiology ; Sperm-Ovum Interactions/physiology ; Spermatozoa/*cytology ; }, abstract = {Several lineages have independently evolved from isogamy (all sexes producing similar gametes) through anisogamy (dissimilar gametes) to the familiar male (producing sperm) and female (producing eggs) condition of most large, multicellular organisms (oogamy). A variety of hypotheses explaining the selective mechanisms causing such evolution and the success of these lineages have been proposed, but little evidence and some confusion persists. Here, a few simplifying assumptions are used to extract and compare the essential features of the various ecological hypotheses. The comparisons reveal that the critical need is to identify a selective advantage of large, immobile gametes (eggs). Assumptions about the effect of sperm size on swimming speed are not important. The classic assumption of increasing zygote success with large size requires a relationship even stronger than survival proportional to volume, which seems unlikely and lacks empirical support. An assumption that eggs produce a pheromone sperm attractant leads, by established physical principles, to a more than sufficient advantage of large egg size. Without pheromones, combinations of increased target size and weaker increased zygote fitness or increased gamete longevity also provide sufficient selection.}, } @article {pmid12386342, year = {2002}, author = {Hughes, KA and Alipaz, JA and Drnevich, JM and Reynolds, RM}, title = {A test of evolutionary theories of aging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {99}, number = {22}, pages = {14286-14291}, pmid = {12386342}, issn = {0027-8424}, support = {R03 HS35793/HS/AHRQ HHS/United States ; }, mesh = {Aging/*genetics/physiology ; Animals ; Drosophila melanogaster/*genetics/physiology ; *Evolution, Molecular ; Female ; Inbreeding ; Male ; Reproduction/physiology ; }, abstract = {Senescence is a nearly universal feature of multicellular organisms, and understanding why it occurs is a long-standing problem in biology. The two leading theories posit that aging is due to (i) pleiotropic genes with beneficial early-life effects but deleterious late-life effects ("antagonistic pleiotropy") or (ii) mutations with purely deleterious late-life effects ("mutation accumulation"). Previous attempts to distinguish these theories have been inconclusive because of a lack of unambiguous, contrasting predictions. We conducted experiments with Drosophila based on recent population-genetic models that yield contrasting predictions. Genetic variation and inbreeding effects increased dramatically with age, as predicted by the mutation theory. This increase occurs because genes with deleterious effects with a late age of onset are unopposed by natural selection. Our findings provide the strongest support yet for the mutation theory.}, } @article {pmid12382328, year = {2002}, author = {Furusawa, C and Kaneko, K}, title = {Origin of multicellular organisms as an inevitable consequence of dynamical systems.}, journal = {The Anatomical record}, volume = {268}, number = {3}, pages = {327-342}, doi = {10.1002/ar.10164}, pmid = {12382328}, issn = {0003-276X}, mesh = {Algorithms ; *Biological Evolution ; *Cell Aggregation ; Cell Communication/physiology ; Cell Differentiation ; Cell Physiological Phenomena ; Computer Simulation ; Models, Biological ; *Morphogenesis ; *Origin of Life ; Stem Cells ; *Systems Theory ; }, abstract = {The origin of multicellular organisms is studied by considering a cell system that satisfies minimal conditions, that is, a system of interacting cells with intracellular biochemical dynamics, and potentiality in reproduction. Three basic features in multicellular organisms-cellular diversification, robust developmental process, and emergence of germ-line cells-are found to be general properties of such a system. Irrespective of the details of the model, such features appear when there are complex oscillatory dynamics of intracellular chemical concentrations. Cells differentiate from totipotent stem cells into other cell types due to instability in the intracellular dynamics with cell-cell interactions, as explained by our isologous diversification theory (Furusawa and Kaneko, 1998a; Kaneko and Yomo, 1997). This developmental process is shown to be stable with respect to perturbations, such as molecular fluctuations and removal of some cells. By further imposing an adequate cell-type-dependent adhesion force, some cells are released, from which the next generation cell colony is formed, and a multicellular organism life-cycle emerges without any finely tuned mechanisms. This recursive production of multicellular units is stabilized if released cells are few in number, implying the separation of germ cell lines. Furthermore, such an organism with a variety of cellular states and robust development is found to maintain a larger growth speed as an ensemble by achieving a cooperative use of resources, compared to simple cells without differentiation. Our results suggest that the emergence of multicellular organisms is not a "difficult problem" in evolution, but rather is a natural consequence of a cell colony that can grow continuously.}, } @article {pmid12382326, year = {2002}, author = {Exposito, JY and Cluzel, C and Garrone, R and Lethias, C}, title = {Evolution of collagens.}, journal = {The Anatomical record}, volume = {268}, number = {3}, pages = {302-316}, doi = {10.1002/ar.10162}, pmid = {12382326}, issn = {0003-276X}, mesh = {Animals ; *Biological Evolution ; *Collagen/chemistry/classification/physiology ; Evolution, Molecular ; Extracellular Matrix/chemistry/*physiology ; Extracellular Matrix Proteins/chemistry ; Models, Biological ; }, abstract = {The extracellular matrix is often defined as the substance that gives multicellular organisms (from plants to vertebrates) their structural integrity, and is intimately involved in their development. Although the general functions of extracellular matrices are comparable, their compositions are quite distinct. One of the specific components of metazoan extracellular matrices is collagen, which is present in organisms ranging from sponges to humans. By comparing data obtained in diploblastic, protostomic, and deuterostomic animals, we have attempted to trace the evolution of collagens and collagen-like proteins. Moreover, the collagen story is closely involved with the emergence and evolution of metazoa. The collagen triple helix is one of numerous modules that arose during the metazoan radiation which permit the formation of large multimodular proteins. One of the advantages of this module is its involvement in oligomerization, in which it acts as a structural organizer that is not only relatively resistant to proteases but also permits the creation of multivalent supramolecular networks.}, } @article {pmid12379496, year = {2002}, author = {Baker, ME}, title = {Albumin, steroid hormones and the origin of vertebrates.}, journal = {The Journal of endocrinology}, volume = {175}, number = {1}, pages = {121-127}, doi = {10.1677/joe.0.1750121}, pmid = {12379496}, issn = {0022-0795}, mesh = {Adrenal Cortex Hormones/physiology ; Animals ; *Biological Evolution ; Glucocorticoids/*metabolism ; Gonadal Steroid Hormones/physiology ; Humans ; Protein Binding ; Receptors, Glucocorticoid/*physiology ; Serum Albumin/*metabolism ; Vertebrates/*physiology ; }, abstract = {Albumin, the major serum protein, binds a wide variety of lipophilic compounds including steroids, other lipophilic hormones and various phytochemicals and xenobiotics that bind to receptors for steroids and other lipophilic hormones. Despite albumin's low affinity (K(d) approximately 10(-4) M to 10(-6) M) for these lipophilic compounds, the high concentration of albumin in serum makes this protein a major carrier of steroids and lipophilic hormones and a regulator of their access to receptors. Albumin also functions as a sink for xenobiotics, diminishing the binding of xenobiotics to hormone receptors and other cellular proteins. This protects animals from endocrine disruption by xenobiotics. We propose that these properties of albumin were important in protochordates and primitive vertebrates, such as jawless fish, about 600 to 530 million years ago, just before and during the Cambrian period. It is at that time that the ancestral receptors of adrenal and sex steroids - androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins - arose in multicellular animals. Albumin regulated access of steroids to their receptors, as well as protecting animals from endocrine disruptors, such as phytochemicals, fungal chemicals and phenolics, and other chemicals formed at hydrothermal vents by geochemical processes. Thus, animals in which albumin expression was high had a selective advantage in regulating the steroid response and avoiding endocrine disruption by xenobiotics.}, } @article {pmid12354665, year = {2002}, author = {Müller, WE and Böhm, M and Grebenjuk, VA and Skorokhod, A and Müller, IM and Gamulin, V}, title = {Conservation of the positions of metazoan introns from sponges to humans.}, journal = {Gene}, volume = {295}, number = {2}, pages = {299-309}, doi = {10.1016/s0378-1119(02)00690-x}, pmid = {12354665}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Calcium-Binding Proteins/genetics ; Conserved Sequence/*genetics ; DNA/chemistry/genetics ; DNA-Binding Proteins ; Humans ; Introns/*genetics ; JNK Mitogen-Activated Protein Kinases ; Microfilament Proteins ; Mitogen-Activated Protein Kinases/genetics ; Molecular Sequence Data ; Phylogeny ; Porifera/*genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; p38 Mitogen-Activated Protein Kinases ; }, abstract = {Sponges (phylum Porifera) are the phylogenetic oldest Metazoa still extant. They can be considered as reference animals (Urmetazoa) for the understanding of the evolutionary processes resulting in the creation of Metazoa in general and also for the metazoan gene organization in particular. In the marine sponge Suberites domuncula, genes encoding p38 and JNK kinases contain nine and twelve introns, respectively. Eight introns in both genes share the same positions and the identical phases. One p38 intron slipped for six bases and the JNK gene has three more introns. However, the sequences of the introns are not conserved and the introns in JNK gene are generally much longer. Introns interrupt most of the conserved kinase subdomains I-XI and are found in all three phases (0, 1 and 2). We analyzed in details p38 and JNK genes from human, Caenorhabditis elegans and Drosophila melanogaster and found in most genes introns at the positions identical to those in sponge genes. The exceptions are two p38 genes from D. melanogaster that have lost all introns in the coding sequence. The positions of 11 introns in each of four human p38 genes are fully conserved and ten introns occupy identical positions as the introns in sponge p38 or JNK genes. The same is true for nine, out of ten introns in the human JNK-1 gene. The introns in human p38 and JNK genes are on average more than ten times longer than corresponding introns in sponges. It was proposed that yeast HOG1-like kinases (from i.e. Saccharomyces cerevisiae and Emericella nidulans) and metazoan p38 and JNK kinases are orthologues. p38 and JNK genes were created after the split from fungi by the duplication and diversification of the HOG1-like progenitor gene. Our results further support the common origin of p38 and JNK genes and speak in favor of a very early time of duplication. The ancestral gene contained at least ten introns, which are still present at the very conserved positions in p38 and JNK genes of extant animals. Four of these introns are present at the same positions in the HOG-like gene in the fungus E. nidulans. The others probably entered the ancestral gene after the split of fungi, but before the duplication of the gene and before the creation of the common, urmetazoan progenitor of all multicellular animals. A second gene coding for an immune molecule is described, the allograft inflammatory factor, which likewise showed a highly conserved exon/intron structure in S. domuncula and in human. These data show that the intron/exon borders are highly conserved in genes from sponges to human.}, } @article {pmid12353296, year = {2002}, author = {Blackburn, DG and Vitt, LJ}, title = {Specializations of the chorioallantoic placenta in the Brazilian scincid lizard, Mabuya heathi: a new placental morphotype for reptiles.}, journal = {Journal of morphology}, volume = {254}, number = {2}, pages = {121-131}, doi = {10.1002/jmor.10005}, pmid = {12353296}, issn = {0362-2525}, mesh = {Allantois/*ultrastructure ; Animals ; Biological Evolution ; Chorion/*ultrastructure ; Female ; Gestational Age ; Lizards/*anatomy & histology ; Placenta/*anatomy & histology ; Pregnancy ; Uterus/anatomy & histology ; }, abstract = {New World skinks of the genus Mabuya exhibit a unique form of viviparity that involves ovulation of tiny (1 mm) eggs and provision of virtually all of the nutrients for embryonic development by placental means. Studies of the Brazilian species M. heathi reveal that the chorioallantoic placenta is unlike those reported in any other squamate genus and exhibits striking specializations for maternal-fetal nutrient transfer. The uterine lining is intimately apposed to the chorioallantois, with no trace of an intervening shell membrane or of epithelial erosion; thus, the placenta is epitheliochorial. The uterus exhibits multicellular glands that secrete organic material into the uterine lumen. Opposite the openings of these glands, the chorion develops areolae, invaginated pits that are lined by absorptive, columnar epithelium. A single, mesometrial placentome develops, formed by radially oriented uterine folds that project into a deep invagination of the chorion. Uterine epithelium of the placentome appears to be syncytial and secretory and overlies a rich vascular supply. The apposed chorionic epithelium is absorptive in morphology and contains giant binucleated cells that bear microvilli. Several specializations of the placental membranes of M. heathi are found among eutherian mammals, signifying evolutionary convergence that extends to histological and cytological levels. The chorioallantoic placenta of M. heathi and its relatives warrants recognition as a new morphotype for reptiles, defined here as the "Type IV" placenta. This is the first new type of chorioallantoic placenta to be defined formally for reptiles in over half a century.}, } @article {pmid12325127, year = {2002}, author = {Money, NP}, title = {Mushroom stem cells.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {24}, number = {10}, pages = {949-952}, doi = {10.1002/bies.10160}, pmid = {12325127}, issn = {0265-9247}, mesh = {Agaricales/*cytology/physiology ; Cell Differentiation ; Cell Division ; Cell Lineage ; Fungi/*cytology/*physiology ; Phylogeny ; }, abstract = {Contrary to the rarity of totipotent cells in animals, almost every cell formed by a fungus can function as a "stem cell". The multicellular fruiting bodies of basidiomycete fungi consist of the same kind of filamentous hyphae that form the feeding phase, or mycelium, of the organism, and visible cellular differentiation is almost nonexistent. Mushroom primordia develop from masses of converging hyphae, and the stipe (or stem), cap, and gills are clearly demarcated within the embryonic fruiting body long before the organ expands and unfolds through water uptake and cell wall loosening. Though frequent references are made to gilled mushrooms in this article, the totipotent nature of fruiting body cells and lack of meristems is also applicable to basidiomycetes that spread their spore-producing tissues inside tubes (e.g., boletes), over spines and rippled surfaces, or form spores in cavities within the fruiting body. Even in the mature mushroom, every hypha retains its totipotency. Among animals, only sponges exhibit a similar degree of developmental flexibility, which is interesting, because these simple metazoans may be relatively close relatives of fungi.}, } @article {pmid12242490, year = {2002}, author = {Anctil, M and Hurtubise, P and Gillis, MA}, title = {Tyrosine hydroxylase and dopamine-beta-hydroxylase immunoreactivities in the cnidarian Renilla koellikeri.}, journal = {Cell and tissue research}, volume = {310}, number = {1}, pages = {109-117}, doi = {10.1007/s00441-002-0601-4}, pmid = {12242490}, issn = {0302-766X}, mesh = {Adrenal Glands/enzymology ; Animals ; Anthozoa/cytology/*enzymology ; Antibody Specificity/immunology ; Catecholamines/*biosynthesis ; Cell Size/physiology ; Cross Reactions/immunology ; Dopamine beta-Hydroxylase/metabolism ; Ectoderm/cytology ; Endoderm/cytology ; Immunohistochemistry ; Mice ; Nerve Net/cytology/*enzymology ; Nervous System/cytology/*enzymology ; Neurites/enzymology/ultrastructure ; Neurons, Afferent/cytology/*enzymology ; Phylogeny ; Species Specificity ; Tyrosine 3-Monooxygenase/metabolism ; }, abstract = {Western Blot and immunohistochemical studies were conducted in the sea pansy Renilla koellikeri, a representative of the earliest multicellular animals with a nervous system, using various antibodies raised against enzymes of the catecholamine biosynthetic pathway. Western blots of sea pansy extracts revealed a protein band that co-migrated with dopamine-beta-hydroxylase (DBH) from mouse adrenal glands. Similar experiments with antisera against tyrosine hydroxylase (TH) revealed several immunoreactive protein bands, all of larger molecular weight than mammalian tyrosine hydroxylase. DBH-like and, to a lesser extent, TH-like and phenylethanolamine N-methyltransferase-like immunoreactivities were detected in ectodermal sensory neurons and associated subectodermal neurites, in neurons of the mesogleal nerve-net and associated amoebocytes, and in some endodermal neurons. While it is still not clear whether the detected TH-immunoreactive proteins represent some form of TH, the presence in sea pansies of a DBH-like protein is in agreement with previously detected norepinephrine-like immunoreactivity in the same species. The widespread distribution of these immunoreactivities in various sea pansy neurons suggests important roles for catecholamines in nerve net activity.}, } @article {pmid12223272, year = {2002}, author = {Hirabayashi, J and Hashidate, T and Arata, Y and Nishi, N and Nakamura, T and Hirashima, M and Urashima, T and Oka, T and Futai, M and Muller, WE and Yagi, F and Kasai, K}, title = {Oligosaccharide specificity of galectins: a search by frontal affinity chromatography.}, journal = {Biochimica et biophysica acta}, volume = {1572}, number = {2-3}, pages = {232-254}, doi = {10.1016/s0304-4165(02)00311-2}, pmid = {12223272}, issn = {0006-3002}, mesh = {Animals ; Antigens, Differentiation/chemistry ; Binding Sites ; Carbohydrate Sequence ; Chromatography, Affinity/instrumentation/*methods ; Galactosides/*chemistry ; Galectin 1 ; Galectin 3 ; Galectins ; Hemagglutinins/*chemistry/classification ; Humans ; Lectins/chemistry ; Molecular Sequence Data ; Molecular Structure ; Oligosaccharides/*chemistry ; Phylogeny ; }, abstract = {Galectins are widely distributed sugar-binding proteins whose basic specificity for beta-galactosides is conserved by evolutionarily preserved carbohydrate-recognition domains (CRDs). Although they have long been believed to be involved in diverse biological phenomena critical for multicellular organisms, in only few a cases has it been proved that their in vivo functions are actually based on specific recognition of the complex carbohydrates expressed on cell surfaces. To obtain clues to understand the physiological roles of diverse members of the galectin family, detailed analysis of their sugar-binding specificity is necessary from a comparative viewpoint. For this purpose, we recently reinforced a conventional system for frontal affinity chromatography (FAC) [J. Chromatogr., B, Biomed. Sci. Appl. 771 (2002) 67-87]. By using this system, we quantitatively analyzed the interactions at 20 degrees C between 13 galectins including 16 CRDs originating from mammals, chick, nematode, sponge, and mushroom, with 41 pyridylaminated (PA) oligosaccharides. As a result, it was confirmed that galectins require three OH groups of N-acetyllactosamine, as had previously been denoted, i.e., 4-OH and 6-OH of Gal, and 3-OH of GlcNAc. As a matter of fact, no galectin could bind to glycolipid-type glycans (e.g., GM2, GA2, Gb3), complex-type N-glycans, of which both 6-OH groups are sialylated, nor Le-related antigens (e.g., Le(x), Le(a)). On the other hand, considerable diversity was observed for individual galectins in binding specificity in terms of (1) branching of N-glycans, (2) repeating of N-acetyllactosamine units, or (3) substitutions at 2-OH or 3-OH groups of nonreducing terminal Gal. Although most galectins showed moderately enhanced affinity for branched N-glycans or repeated N-acetyllactosamines, some of them had extremely enhanced affinity for either of these multivalent glycans. Some galectins also showed particular preference for alpha1-2Fuc-, alpha1-3Gal-, alpha1-3GalNAc-, or alpha2-3NeuAc-modified glycans. To summarize, galectins have evolved their sugar-binding specificity by enhancing affinity to either "branched", "repeated", or "substituted" glycans, while conserving their ability to recognize basic disaccharide units, Galbeta1-3/4GlcNAc. On these bases, they are considered to exert specialized functions in diverse biological phenomena, which may include formation of local cell-surface microdomains (raft) by sorting glycoconjugate members for each cell type.}, } @article {pmid12200871, year = {2000}, author = {Meyerowitz, EM}, title = {The plant plan: multicellular life in the other Kingdom.}, journal = {Harvey lectures}, volume = {96}, number = {}, pages = {51-72}, pmid = {12200871}, issn = {0073-0874}, mesh = {Animals ; Arabidopsis/cytology/genetics/growth & development ; Biological Evolution ; Body Patterning/genetics ; Cell Communication/genetics ; Genome, Plant ; Models, Biological ; *Plant Cells ; Plant Development ; Plants/*genetics ; }, abstract = {One must conclude, then, that plants and animals may have evolved in quite different fashions. There is no doubt that they have independently evolved development, and this is demonstrated by the nonhomology of genes serving identical developmental functions in prepattern formation. There is nonetheless also no doubt that plants and animals have evolved from a common eukaryotic ancestor, as indicated by the clear homology of the genes that control the chromatin level of gene regulation. There is also little doubt that some developmentally important genes of plants, such as the ethylene and red light receptors, have derived from an event of horizontal evolutionary transfer specific to plants. And it is at least possible to think that the variation on which Darwinian evolution acts in plants results in part from phenomena that are not seen in animals, namely, the controlled appearance and Mendelian inheritance of epigenetically silenced genes. Genomic and genetic analyses of plants thus reveal a type of organism with familiar features, but profound differences from the more-studied animals. Only by further study of plants and of animals can we fully understand the differences between plants and animals, and consequently distinguish between those features of developmental pattern formation and cellular signaling that are necessary aspects of complex organisms, and those that are accidents of evolutionary history.}, } @article {pmid12190988, year = {2002}, author = {Kawli, T and Venkatesh, BR and Kennady, PK and Pande, G and Nanjundiah, V}, title = {Correlates of developmental cell death in Dictyostelium discoideum.}, journal = {Differentiation; research in biological diversity}, volume = {70}, number = {6}, pages = {272-281}, doi = {10.1046/j.1432-0436.2002.700605.x}, pmid = {12190988}, issn = {0301-4681}, mesh = {Animals ; Annexin A5/analysis ; *Apoptosis/drug effects/physiology ; Biological Evolution ; Calcium/pharmacology ; Caspase 3 ; Caspases/analysis ; Cell Membrane Permeability ; Cell Nucleus/ultrastructure ; DNA Fragmentation ; DNA, Protozoan/chemistry ; Dictyostelium/*cytology/growth & development ; Intracellular Membranes/physiology ; Membrane Lipids/analysis ; Membrane Potentials ; Phosphatidylserines/analysis ; Protozoan Proteins/analysis ; }, abstract = {We have studied the correlates of cell death during stalk cell differentiation in Dictyostelium discoideum. Our main findings are four. (i) There is a gradual increase in the number of cells with exposed phosphatidyl serine residues, an indicator of membrane asymmetry loss and increased permeability. Only presumptive stalk cells show this change in membrane asymmetry. Cells also show an increase in cell membrane permeability under conditions of calcium-induced stalk cell differentiation in cell monolayers. (ii) There is a gradual fall in mitochondrial membrane potential during development, again restricted to the presumptive stalk cells. (iii) The fraction of cells showing caspase-3 activity increases as development proceeds and then declines in the terminally differentiated fruiting body. (iv) There is no internucleosomal cleavage of DNA, or DNA fragmentation, in D. discoideum nor is there any calcium- and magnesium-dependent endonucleolytic activity in nuclear extracts from various developmental stages. However, nuclear condensation and peripheralization does occur in stalk cells. Thus, cell death in D. discoideum shows some, but not all, features of apoptotic cell death as recognized in other multicellular systems. These findings argue against the emergence of a single mechanism of 'programmed cell death (PCD)' before multicellularity arose during evolution.}, } @article {pmid12176051, year = {2002}, author = {Thorpe, C and Hoober, KL and Raje, S and Glynn, NM and Burnside, J and Turi, GK and Coppock, DL}, title = {Sulfhydryl oxidases: emerging catalysts of protein disulfide bond formation in eukaryotes.}, journal = {Archives of biochemistry and biophysics}, volume = {405}, number = {1}, pages = {1-12}, doi = {10.1016/s0003-9861(02)00337-5}, pmid = {12176051}, issn = {0003-9861}, support = {GM26643/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Birds ; Disulfides ; Endoplasmic Reticulum/metabolism ; Extracellular Matrix/metabolism ; Humans ; Immunohistochemistry ; Models, Biological ; Models, Genetic ; Models, Molecular ; Molecular Sequence Data ; Multigene Family ; Oxidoreductases/*metabolism/*physiology ; Phylogeny ; Saponins ; Sequence Homology, Amino Acid ; Thioredoxins/metabolism ; Trypanosoma ; }, abstract = {Members of the Quiescin-sulfhydryl oxidase (QSOX) family utilize a thioredoxin domain and a small FAD-binding domain homologous to the yeast ERV1p protein to oxidize sulfhydryl groups to disulfides with the reduction of oxygen to hydrogen peroxide. QSOX enzymes are found in all multicellular organisms for which complete genomes exist and in Trypanosoma brucei, but are not found in yeast. The avian QSOX is the best understood enzymatically: its preferred substrates are peptides and proteins, not monothiols such as glutathione. Mixtures of avian QSOX and protein disulfide isomerase catalyze the rapid insertion of the correct disulfide pairings in reduced RNase. Immunohistochemical studies of human tissues show a marked and highly localized concentration of QSOX in cell types associated with heavy secretory loads. Consistent with this role in the formation of disulfide bonds, QSOX is typically found in the cell in the endoplasmic reticulum and Golgi and outside the cell. In sum, this review suggests that QSOX enzymes play a significant role in oxidative folding of a large variety of proteins in a wide range of multicellular organisms.}, } @article {pmid12167399, year = {2002}, author = {Steele, RE}, title = {Developmental signaling in Hydra: what does it take to build a "simple" animal?.}, journal = {Developmental biology}, volume = {248}, number = {2}, pages = {199-219}, doi = {10.1006/dbio.2002.0744}, pmid = {12167399}, issn = {0012-1606}, mesh = {Animals ; *Biological Evolution ; Endothelins/metabolism ; Hydra/enzymology/genetics/*growth & development/*metabolism ; Membrane Proteins/metabolism ; Oligopeptides/genetics/metabolism ; Peptides/metabolism ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Receptors, Notch ; *Signal Transduction ; Transforming Growth Factor beta/metabolism ; Wnt Proteins ; *Zebrafish Proteins ; ras Proteins/genetics/metabolism ; }, abstract = {Developmental processes in multicellular animals depend on an array of signal transduction pathways. Studies of model organisms have identified a number of such pathways and dissected them in detail. However, these model organisms are all bilaterians. Investigations of the roles of signal transduction pathways in the early-diverging metazoan Hydra have revealed that a number of the well-known developmental signaling pathways were already in place in the last common ancestor of Hydra and bilaterians. In addition to these shared pathways, it appears that developmental processes in Hydra make use of pathways involving a variety of peptides. Such pathways have not yet been identified as developmental regulators in more recently diverged animals. In this review I will summarize work to date on developmental signaling pathways in Hydra and discuss the future directions in which such work will need to proceed to realize the potential that lies in this simple animal.}, } @article {pmid12145714, year = {2002}, author = {Gagnon, SN and Hengartner, MO and Desnoyers, S}, title = {The genes pme-1 and pme-2 encode two poly(ADP-ribose) polymerases in Caenorhabditis elegans.}, journal = {The Biochemical journal}, volume = {368}, number = {Pt 1}, pages = {263-271}, pmid = {12145714}, issn = {0264-6021}, mesh = {Animals ; Caenorhabditis elegans/*enzymology/genetics ; Cloning, Molecular ; DNA, Complementary/analysis ; Gene Expression Regulation ; Genes, Helminth/*genetics ; Molecular Sequence Data ; Poly Adenosine Diphosphate Ribose/biosynthesis ; Poly(ADP-ribose) Polymerases/*genetics ; RNA, Messenger/analysis ; Recombinant Proteins/metabolism ; }, abstract = {Poly(ADP-ribose) polymerases (PARPs) are an expanding, well-conserved family of enzymes found in many metazoan species, including plants. The enzyme catalyses poly(ADP-ribosyl)ation, a post-translational modification that is important in DNA repair and programmed cell death. In the present study, we report the finding of an endogenous source of poly(ADP-ribosyl)ation in total extracts of the nematode Caenorhabditis elegans. Two cDNAs encoding highly similar proteins to human PARP-1 (huPARP-1) and huPARP-2 are described, and we propose to name the corresponding enzymes poly(ADP-ribose) metabolism enzyme 1 (PME-1) and PME-2 respectively. PME-1 (108 kDa) shares 31% identity with huPARP-1 and has an overall structure similar to other PARP-1 subfamily members. It contains sequences having considerable similarity to zinc-finger motifs I and II, as well as with the catalytic domain of huPARP-1. PME-2 (61 kDa) has structural similarities with the catalytic domain of PARPs in general and shares 24% identity with huPARP-2. Recombinant PME-1 and PME-2 display PARP activity, which may partially account for the similar activity found in the worm. A partial duplication of the pme-1 gene with pseudogene-like features was found in the nematode genome. Messenger RNA for pme-1 are 5'-tagged with splice leader 1, whereas those for pme - 2 are tagged with splice leader 2, suggesting an operon-like expression for pme - 2. The expression pattern of pme-1 and pme-2 is also developmentally regulated. Together, these results show that PARP-1 and -2 are conserved in evolution and must have important functions in multicellular organisms. We propose using C. elegans as a model to understand better the functions of these enzymes.}, } @article {pmid12142278, year = {2002}, author = {True, JR and Carroll, SB}, title = {Gene co-option in physiological and morphological evolution.}, journal = {Annual review of cell and developmental biology}, volume = {18}, number = {}, pages = {53-80}, doi = {10.1146/annurev.cellbio.18.020402.140619}, pmid = {12142278}, issn = {1081-0706}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Body Patterning/*genetics ; *Evolution, Molecular ; Gene Duplication ; Gene Expression Regulation, Developmental/*genetics ; Genes/*genetics ; Genetic Variation/genetics ; Humans ; }, abstract = {Co-option occurs when natural selection finds new uses for existing traits, including genes, organs, and other body structures. Genes can be co-opted to generate developmental and physiological novelties by changing their patterns of regulation, by changing the functions of the proteins they encode, or both. This often involves gene duplication followed by specialization of the resulting paralogous genes into particular functions. A major role for gene co-option in the evolution of development has long been assumed, and many recent comparative developmental and genomic studies have lent support to this idea. Although there is relatively less known about the molecular basis of co-option events involving developmental pathways, much can be drawn from well-studied examples of the co-option of structural proteins. Here, we summarize several case studies of both structural gene and developmental genetic circuit co-option and discuss how co-option may underlie major episodes of adaptive change in multicellular organisms. We also examine the phenomenon of intraspecific variability in gene expression patterns, which we propose to be one form of material for the co-option process. We integrate this information with recent models of gene family evolution to provide a framework for understanding the origin of co-optive evolution and the mechanisms by which natural selection promotes evolutionary novelty by inventing new uses for the genetic toolkit.}, } @article {pmid12140322, year = {2002}, author = {Conant, GC and Wagner, A}, title = {GenomeHistory: a software tool and its application to fully sequenced genomes.}, journal = {Nucleic acids research}, volume = {30}, number = {15}, pages = {3378-3386}, pmid = {12140322}, issn = {1362-4962}, support = {R01 GM063882/GM/NIGMS NIH HHS/United States ; GM063882-01/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/genetics ; Drosophila melanogaster/genetics ; Escherichia coli/genetics ; Evolution, Molecular ; Gene Duplication ; *Genes, Duplicate/physiology ; *Genome ; Genomics/*methods ; Saccharomyces cerevisiae/genetics ; Schizosaccharomyces/genetics ; Sequence Analysis, DNA/*methods ; *Software ; }, abstract = {We present a publicly available software tool (http://www.unm.edu/~compbio/software/GenomeHistory) that identifies all pairs of duplicate genes in a genome and then determines the degree of synonymous and non-synonymous divergence between each duplicate pair. Using this tool, we analyze the relations between (i) gene function and the propensity of a gene to duplicate and (ii) the number of genes in a gene family and the family's rate of sequence evolution. We do so for the complete genomes of four eukaryotes (fission and budding yeast, fruit fly and nematode) and one prokaryote (Escherichia coli). For some classes of genes we observe a strong relationship between gene function and a gene's propensity to undergo duplication. Most notably, ribosomal genes and transcription factors appear less likely to undergo gene duplication than other genes. In both fission and budding yeast, we see a strong positive correlation between the selective constraint on a gene and the size of the gene family of which this gene is a member. In contrast, a weakly negative such correlation is seen in multicellular eukaryotes.}, } @article {pmid12138776, year = {2002}, author = {Odintsova, MS and Iurina, NP}, title = {[The mitochondrial genome of protists].}, journal = {Genetika}, volume = {38}, number = {6}, pages = {773-788}, pmid = {12138776}, issn = {0016-6758}, mesh = {Animals ; Biological Evolution ; Codon ; DNA, Mitochondrial ; Dictyostelium ; Eukaryota/*genetics ; *Genome ; Mitochondria/*genetics ; RNA, Ribosomal ; RNA, Transfer ; }, abstract = {The data on the structure and functions of the mitochondrial genomes of protists (Protozoa and unicellular red and green algae) are reviewed. It is emphasized that mitochondrial gene structure and composition, as well as organization of mitochondrial genomes in protists are more diverse than in multicellular eukaryotes. The gene content of mitochondrial genomes of protists are closer to those of plants than animals or fungi. In the protist mitochondrial DNA, both the universal (as in higher plants) and modified (as in animals and fungi) genetic codes are used. In the overwhelming majority of cases, protist mitochondrial genomes code for the major and minor rRNA components, some tRNAs, and about 30 proteins of the respiratory chain and ribosomes. Based on comparison of the mitochondrial genomes of various protists, the origin and evolution of mitochondria are briefly discussed.}, } @article {pmid12128135, year = {2002}, author = {Rossi, L and Corvò, R}, title = {Retinoic acid modulates the radiosensitivity of head-and-neck squamous carcinoma cells grown in collagen gel.}, journal = {International journal of radiation oncology, biology, physics}, volume = {53}, number = {5}, pages = {1319-1327}, doi = {10.1016/s0360-3016(02)02865-1}, pmid = {12128135}, issn = {0360-3016}, mesh = {Cell Division ; Collagen/metabolism/*pharmacology ; Dose-Response Relationship, Drug ; Endothelium, Vascular/pathology ; Epithelial Cells ; Gels/*pharmacology ; Head and Neck Neoplasms/*radiotherapy ; Humans ; Hyaluronic Acid/pharmacology ; Immunohistochemistry ; Phenotype ; Tetrazolium Salts/pharmacology ; Thiazoles/pharmacology ; Time Factors ; Tretinoin/metabolism/*pharmacology ; Tumor Cells, Cultured ; }, abstract = {PURPOSE: Collagen gels are increasingly regarded as reliable scaffolds for studying cells in vitro, displaying the same three-dimensional network of collagen fibers as encountered in vivo. As a contribution to therapeutic control of head-and-neck cancer, we grew HSCO86 cells in collagen gel and assessed their behavior in the presence of retinoic acid (RA) and radiation.

METHODS AND MATERIALS: The malignant epithelial cell line HSCO86 was isolated from a postirradiation human oropharyngeal squamous carcinoma; it was EGFR-negative by immunocytochemical criteria. The cells were embedded in hydrated collagen I at a density of 10(6) cells/mL, and on Days 8, 10, and 12 of culture, they were treated with 10(-5) M retinoic acid. Radiation was administered using two different schedules: simultaneously with RA in three daily doses totaling 10 Gy, or with a single dose of 8 Gy on Day 29 of culture, after the effects of RA had taken place. Cell proliferation was evaluated by the MTT assay, whereas morphometric characteristics were detected in the cultured gels directly or in the gels after they were fixed and stained with hematoxylin.

RESULTS: Contrary to growth in monolayer, where HSCO86 cells displayed a high proliferation rate, in collagen gel only a tiny fraction of the cells, usually less than 0.02%, survived the environmental stress; these cells spontaneously organized themselves into clonal multicellular spheroids growing up to 0.8 mm in diameter. After exposure to 10(-5) M retinoic acid, cell proliferation first declined and then, about 15 days after treatment, it started to increase to a level far above that in the control group. This surge in proliferation was ascribed to the appearance of numerous fibroblast-like cells at the edge of the spheroids. These cells, called HSCO-F, were the result of epithelial-to-mesenchymal conversion. When the gels were disaggregated by collagenase, and the cells were seeded in monolayer, HSCO-F cells reversed their morphology into parental HSCO86 cells. Treatment of collagen gels with 10 Gy, fractionated in three daily doses, did not substantially affect the growth of HSCO86 spheroids. However, when radiation was given simultaneously with RA, cell growth was significantly inhibited, both in terms of cell proliferation and size of spheroids (p < 0.0001 vs. untreated controls). This synergism applied mainly to parental HSCO86 cells, because no significant damage was induced by radiation on the HSCO-F cells previously generated by treatment with RA.

CONCLUSION: Differences in the radiosensitivity of HSCO86 and HSCO-F cells are surprising in view of their common origin; this suggests a scenario in which, to overcome a microenvironmental stress, head-and-neck carcinoma cells can temporarily shift from an epithelial to a mesenchymal phenotype. In particular, morphologic and functional data suggested that HSCO-F cells were transformed into vascular endothelial cells whose characteristics included the following: (1) distinctive expression of Factor VIII and beta(1)-integrin, not detected in parental HSCO86 cells; (2) active migration in the collagen network by extruded pseudopodia, frequently appearing as colonies of filamentous cells aligned along the radial axis of the spheroids; and (3) efficient contraction of floating collagen gels. The implication of our study is that head-and-neck carcinomas may respond to RA treatment by selecting cell populations both resistant to radiation and capable of migrating inside the connective tissue, mimicking the behavior of vascular capillaries.}, } @article {pmid12116757, year = {2002}, author = {Akmaev, IG and Volkova, OV and Grinevich, VV and Resnenko, AB}, title = {[Evolutionary aspects of a stress reaction].}, journal = {Vestnik Rossiiskoi akademii meditsinskikh nauk}, volume = {}, number = {6}, pages = {25-27}, pmid = {12116757}, issn = {0869-6047}, mesh = {Animals ; *Biological Evolution ; Cnidaria/*physiology ; Mammals/*physiology ; Neuroimmunomodulation ; Neurosecretory Systems/metabolism/physiology/physiopathology ; Stress, Physiological/immunology/metabolism/*physiopathology ; }, abstract = {Interconnections between the integrative systems, such as nervous, endocrine, and immune ones, are clearly seen during a stress response. The sources of such a cooperation should be sought at the earliest stages of evolution of multicellular organisms. The paper deals with the main points of the formation of a stress response and the development of the systems involved in this process. Based on the data available in the literature and their own findings, the authors conclude that just primitive multicellular organisms, such as coelenterates, have hemolymph cells (chemocytes) that combines the properties of all regulatory systems of more highly organized species. However, the need for such cells no longer arises afterwards. Glucocorticoids, one of the major stress hormones, show up during the development of a stress response relatively late--in fish. While in fish, the production of ACTH and glucocorticoids in the pituitary cells is under urotensin control, this function belongs to corticotropin-releasing hormone of pituitary origin in more advanced animals. The predominant value of corticotropin-releasing hormone simultaneously occurs with the development of the pituitary portal vascular system. Such transformations lead to the formation of the hierarchically arranged neuroendocrine axes that are responsible for showing a stress response, on the one hand, and to the development of qualitatively new interactions between the nervous, endocrine, and immune systems, on the other.}, } @article {pmid12096807, year = {2002}, author = {Heinrich, G and Pfeifhofer, HW and Stabentheiner, E and Sawidis, T}, title = {Glandular hairs of Sigesbeckia jorullensis Kunth (Asteraceae): morphology, histochemistry and composition of essential oil.}, journal = {Annals of botany}, volume = {89}, number = {4}, pages = {459-469}, pmid = {12096807}, issn = {0305-7364}, mesh = {Asteraceae/chemistry/*metabolism/ultrastructure ; Calcium/metabolism ; Calcium Oxalate/metabolism ; Cell Surface Extensions/chemistry/ultrastructure ; Chloroplasts/ultrastructure ; Diterpenes/metabolism ; Flavonoids/metabolism ; Hydrolyzable Tannins/metabolism ; Iron/metabolism ; Magnesium/metabolism ; Manganese/metabolism ; Microscopy, Electron, Scanning ; Oils, Volatile/*analysis ; Plant Structures/chemistry/*metabolism/ultrastructure ; Potassium/metabolism ; Sesquiterpenes/metabolism ; *Sesquiterpenes, Germacrane ; Sodium/metabolism ; }, abstract = {Long-stalked glandular hairs of outer and inner involucral bracts of Sigesbeckia jorullensis, which are important for epizoic fruit propagation, were investigated using light and scanning electron microscopy. The essential oil secreted by the hairs was analysed by chromatographic methods including gas chromatography/mass spectrometry and with a laser microprobe mass analyser. The glandular hairs consisted of a large multicellular stalk and a multicellular secreting head. The apical layer of glandular head cells was characterized by leucoplasts and calcium oxalate crystals. Below the apical cells there were up to six layers of cells containing many chloroplasts around the nucleus and surrounded by vacuoles filled with flavonoids and tannins. The essential oil originating in the head cells was secreted into the subcuticular space and may be liberated by rupture of the cuticle. It was mainly composed of sesqui- and diterpenes, with the sesquiterpene hydrocarbon germacrene-D as the main component. Monoterpenes, n-alkanes and their derivatives as well as flavonoid aglycones were also detected. The stickiness of the essential oil is probably associated with the high content of oxygenated sesqui- and diterpenes. In addition to long-stalked trichomes, small biseriate trichomes occurred, secreting small quantities of essential oil into a subcuticular space.}, } @article {pmid12093377, year = {2002}, author = {Ledent, V and Paquet, O and Vervoort, M}, title = {Phylogenetic analysis of the human basic helix-loop-helix proteins.}, journal = {Genome biology}, volume = {3}, number = {6}, pages = {RESEARCH0030}, pmid = {12093377}, issn = {1474-760X}, mesh = {Animals ; Avian Proteins/chemistry/genetics ; Caenorhabditis elegans ; Chickens ; Computational Biology ; Databases, Protein ; Drosophila melanogaster ; Evolution, Molecular ; Helix-Loop-Helix Motifs/*genetics ; Helminth Proteins/chemistry/genetics ; Humans ; Insect Proteins/chemistry/genetics ; Mice ; *Phylogeny ; Proteins/chemistry/*genetics ; }, abstract = {BACKGROUND: The basic helix-loop-helix (bHLH) proteins are a large and complex multigene family of transcription factors with important roles in animal development, including that of fruitflies, nematodes and vertebrates. The identification of orthologous relationships among the bHLH genes from these widely divergent taxa allows reconstruction of the putative complement of bHLH genes present in the genome of their last common ancestor.

RESULTS: We identified 39 different bHLH genes in the worm Caenorhabditis elegans, 58 in the fly Drosophila melanogaster and 125 in human (Homo sapiens). We defined 44 orthologous families that include most of these bHLH genes. Of these, 43 include both human and fly and/or worm genes, indicating that genes from these families were already present in the last common ancestor of worm, fly and human. Only two families contain both yeast and animal genes, and no family contains both plant and animal bHLH genes. We suggest that the diversification of bHLH genes is directly linked to the acquisition of multicellularity, and that important diversification of the bHLH repertoire occurred independently in animals and plants.

CONCLUSIONS: As the last common ancestor of worm, fly and human is also that of all bilaterian animals, our analysis indicates that this ancient ancestor must have possessed at least 43 different types of bHLH, highlighting its genomic complexity.}, } @article {pmid12082148, year = {2002}, author = {Derrien, V and Couillault, C and Franco, M and Martineau, S and Montcourrier, P and Houlgatte, R and Chavrier, P}, title = {A conserved C-terminal domain of EFA6-family ARF6-guanine nucleotide exchange factors induces lengthening of microvilli-like membrane protrusions.}, journal = {Journal of cell science}, volume = {115}, number = {Pt 14}, pages = {2867-2879}, doi = {10.1242/jcs.115.14.2867}, pmid = {12082148}, issn = {0021-9533}, mesh = {ADP-Ribosylation Factor 6 ; ADP-Ribosylation Factors/genetics/*metabolism ; Actin Cytoskeleton/genetics/metabolism ; Animals ; Catalytic Domain/genetics ; Cell Compartmentation/genetics ; Cell Membrane/*metabolism/ultrastructure ; Cell Movement/physiology ; Cell Size/physiology ; Cells, Cultured ; Cloning, Molecular ; Cricetinae ; Eukaryotic Cells/*metabolism/ultrastructure ; Evolution, Molecular ; Green Fluorescent Proteins ; Guanine Nucleotide Exchange Factors/genetics/*isolation & purification ; Luminescent Proteins ; Microscopy, Electron, Scanning ; Microvilli/*metabolism/ultrastructure ; Molecular Sequence Data ; Peptide Elongation Factors/genetics/*isolation & purification ; Phylogeny ; Protein Structure, Tertiary/genetics ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; }, abstract = {We recently reported the identification of EFA6 (exchange factor for ARF6), a brain-specific Sec7-domain-containing guanine nucleotide exchange factor that works specifically on ARF6. Here, we have characterized the product of a broadly expressed gene encoding a novel 1056 amino-acid protein that we have named EFA6B. We show that EFA6B, which contains a Sec7 domain that is highly homologous to EFA6, works as an ARF6-specific guanine exchange factor in vitro. Like EFA6, which will be referred to as EFA6A from now on, EFA6B is involved in membrane recycling and colocalizes with ARF6 in actin-rich membrane ruffles and microvilli-like protrusions on the dorsal cell surface in transfected baby hamster kidney cells. Strikingly, homology between EFA6A and EFA6B is not limited to the Sec7 domain but extends to an adjacent pleckstrin homology (PH) domain and a approximately 150 amino-acid C-terminal region containing a predicted coiled coil motif. Association of EFA6A with membrane ruffles and microvilli-like structures depends on the PH domain, which probably interacts with phosphatidylinositol 4,5-biphosphate. Moreover, we show that overexpression of the PH domain/C-terminal region of EFA6A or EFA6B in the absence of the Sec7 domain promotes lengthening of dorsal microvillar protrusions. This morphological change requires the integrity of the coiled-coil motif. Lastly, database analysis reveals that the EFA6-family comprises at least four members in humans and is conserved in multicellular organisms throughout evolution. Our results suggest that EFA6 family guanine exchange factors are modular proteins that work through the coordinated action of the catalytic Sec7 domain to promote ARF6 activation, through the PH domain to regulate association with specific subdomains of the plasma membrane and through the C-terminal region to control actin cytoskeletal reorganization.}, } @article {pmid12072958, year = {2002}, author = {Castán, P and Zafra, O and Moreno, R and de Pedro, MA and Vallés, C and Cava, F and Caro, E and Schwarz, H and Berenguer, J}, title = {The periplasmic space in Thermus thermophilus: evidence from a regulation-defective S-layer mutant overexpressing an alkaline phosphatase.}, journal = {Extremophiles : life under extreme conditions}, volume = {6}, number = {3}, pages = {225-232}, doi = {10.1007/s00792-001-0246-3}, pmid = {12072958}, issn = {1431-0651}, mesh = {Alkaline Phosphatase/genetics/*metabolism ; Base Sequence ; Cloning, Molecular ; DNA Primers ; Microscopy, Confocal ; Microscopy, Electron ; *Mutation ; Periplasm/*enzymology ; Polymerase Chain Reaction ; Thermus thermophilus/*enzymology/genetics/ultrastructure ; }, abstract = {The presence of a periplasmic space within the cell envelope of Thermus thermophilus was analyzed in a mutant (HB8(Delta)UTR1) defective in the regulation of its S-layer (surface crystalline layer). This mutant forms round multicellular bodies (MBs) surrounded by a common envelope as the culture approaches the stationary phase. Confocal microscopy revealed that the origin of the MBs is the progressive detachment of the external layers coupled with the accumulation of NH(2)-containing material between the external envelopes and the peptidoglycan. A specific pattern of proteins was found as soluble components of the intercellular space of the MBs by a single fractionation procedure, suggesting that they are periplasmic-like components. To demonstrate this, we cloned a gene (phoA) from T. thermophilus HB8 encoding a signal peptide-wearing alkaline phosphatase (AP), and engineered it to be overexpressed in the mutant from a shuttle vector. Most of the AP activity (>80%) was found as a soluble component of the MBs' intercellular fraction. All these data indicate that Thermus thermophilus actually has a periplasmic space which is functionally similar to that of Proteobacteria. The potential application of the HB8(Delta)UTR1 mutant for the overexpression of periplasmic thermophilic proteins is discussed.}, } @article {pmid12058178, year = {2000}, author = {Xie, T and Ding, DF}, title = {Conservation and Evolution of the "Core Apoptotic Engine" Lesson from the Genome Comparison of Drosophila.}, journal = {Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica}, volume = {32}, number = {6}, pages = {637-639}, pmid = {12058178}, issn = {0582-9879}, abstract = {Genome comparison is the main approach to deduce regulatory network from genome sequence. Apoptotic network is one kind of typical regulatory networks. EGL1, CED3, CED4, CED9 and their homologous proteins play essential roles in apoptosis of C.elegans and mammals, and were regarded as the components of the"core apoptotic engine". But in fruit fly, Drosophila melanogaster, this network is incomplete. A series of bioinformatic analyses found the lost chains of "core apoptotic engine" by discovering two homologues of BCL2/CED9 and one of EGL1 in fruit fly genome sequences. These findings proved that the "core apoptotic engine" is indeed widely conserved among multicellular organisms and the evolutionary complexity of this network of Drosophila is between that of C.elegans and mammals.}, } @article {pmid12058048, year = {2002}, author = {Yamada, S and Okada, Y and Ueno, M and Iwata, S and Deepa, SS and Nishimura, S and Fujita, M and Van Die, I and Hirabayashi, Y and Sugahara, K}, title = {Determination of the glycosaminoglycan-protein linkage region oligosaccharide structures of proteoglycans from Drosophila melanogaster and Caenorhabditis elegans.}, journal = {The Journal of biological chemistry}, volume = {277}, number = {35}, pages = {31877-31886}, doi = {10.1074/jbc.M205078200}, pmid = {12058048}, issn = {0021-9258}, mesh = {Animals ; Caenorhabditis elegans/genetics/*metabolism ; Carbohydrate Sequence ; Chromatography, Gel ; Chromatography, High Pressure Liquid ; Disaccharides/chemistry ; Drosophila melanogaster/genetics/*metabolism ; Genome ; Glycosaminoglycans/*chemistry/isolation & purification ; Molecular Sequence Data ; Oligosaccharides/*chemistry/isolation & purification ; Proteoglycans/*chemistry/isolation & purification ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Caenorhabditis elegans and Drosophila melanogaster are relevant models for studying the roles of glycosaminoglycans (GAG) during the development of multicellular organisms. The genome projects of these organisms have revealed the existence of multiple genes related to GAG-synthesizing enzymes. Although the putative genes encoding the enzymes that synthesize the GAG-protein linkage region have also been identified, there is no direct evidence that the GAG chains bind covalently to core proteins. This study aimed to clarify whether GAG chains in these organisms are linked to core proteins through the conventional linkage region tetrasaccharide sequence found in vertebrates and whether modifications by phosphorylation and sulfation reported for vertebrates are present also in invertebrates. The linkage region oligosaccharides were isolated from C. elegans chondroitin in addition to D. melanogaster heparan and chondroitin sulfate after digestion with the respective bacterial eliminases and were then derivatized with a fluorophore 2-aminobenzamide. Their structures were characterized by gel filtration and anion-exchange high performance liquid chromatography in conjunction with enzymatic digestion and matrix-assisted laser desorption ionization time-of-flight spectrometry, which demonstrated a uniform linkage tetrasaccharide structure of -GlcUA-Gal-Gal-Xyl- or -GlcUA-Gal-Gal-Xyl(2-O-phosphate)- for C. elegans chondroitin and D. melanogaster CS, respectively. In contrast, the unmodified and phosphorylated counterparts were demonstrated in heparan sulfate of adult flies at a molar ratio of 73:27, and in that of the immortalized D. melanogaster S2 cell line at a molar ratio of 7:93, which suggests that the linkage region in the fruit fly first becomes phosphorylated uniformly on the Xyl residue and then dephosphorylated. It has been established here that GAG chains in both C. elegans and D. melanogaster are synthesized on the core protein through the ubiquitous linkage region tetrasaccharide sequence, suggesting that indispensable functions of the linkage region in the GAG synthesis have been well conserved during evolution.}, } @article {pmid12053774, year = {2002}, author = {Vakhmin, IuB}, title = {[Aging as a metagenetic process].}, journal = {Tsitologiia}, volume = {44}, number = {2}, pages = {218-223}, pmid = {12053774}, issn = {0041-3771}, mesh = {Cellular Senescence/*genetics ; DNA ; Humans ; Meiosis ; Mitosis ; }, abstract = {Genomes of eukaryotic cells are so complicated that spontaneous processes lead inevitably to a continuous formation of egoistic genetic elements from the normal ones. These elements convert the intracellular Cosmos into Chaos and therefore they can be named chaonogenes. They behave as endogenous genetic parasites and are able to evaluate. The rate of their evolution is very rapid, which unevitably results in senescence and death of not only cells and multicellular organisms but also of populations and species, because chaonogens are transmitted from somatic cells to gametes. Populations of chaonogenes are very sensitive to environmental changes, and different sets of intracellular or extracellular changes are commonly used in nature to put obstracles in deleterious evolution of chaonogenes or to stop their evolution. These changes can be moderate (as at mitosis) or crude (as at meiosis), or they can be predicted (as programmed biochemical changes in the course of mitosis, meiosis and gametogenesis) or unpredicred (mutations, somatic crossingover, random association of gamets), but in all the cases they lead eventually to some degree of rejuvenation. In somatic cell populations, the process of senescence in slowed down by means of epigenetically determined changes and mitotic divisions, at which both kinds of changes (programmed and accidental) are moderate, and for this reason only a small part of dividing cells dies. At meiosis both kinds of changes are so acute that the majority of cells die, but the formation of gametes and zygotes becomes almost completely rejuvenated. Only mutations leading to very acute changes in intracellular conditions (whose products act on chaonogenes similarly as new antibiotics on bacteria) can save aging populations of multicellular organisms from death (as do L. N. Gumilev's "mutations of passionarity"), and only accidentally appearing "catastrophic" macromutations can give rise to new (and, of the same time, young) species. It is concluded that the induction of acute temporal biochemical changes in the inner environment is to slow down processes of human senescence and to lead to rejuvenation.}, } @article {pmid12019231, year = {2002}, author = {Mason, DA and Fleming, RJ and Goldfarb, DS}, title = {Drosophila melanogaster importin alpha1 and alpha3 can replace importin alpha2 during spermatogenesis but not oogenesis.}, journal = {Genetics}, volume = {161}, number = {1}, pages = {157-170}, pmid = {12019231}, issn = {0016-6731}, support = {GM40362/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; *Drosophila Proteins ; Drosophila melanogaster/*physiology ; Female ; Fertility/physiology ; Gene Dosage ; Male ; Oogenesis/*physiology ; Ovary/metabolism ; Phosphorylation ; Phylogeny ; Spermatogenesis/*physiology ; Testis/metabolism/ultrastructure ; alpha Karyopherins/*physiology ; }, abstract = {Importin alpha's mediate the nuclear transport of many classical nuclear localization signal (cNLS)-containing proteins. Multicellular animals contain multiple importin alpha genes, most of which fall into three conventional phylogenetic clades, here designated alpha1, alpha2, and alpha3. Using degenerate PCR we cloned Drosophila melanogaster importin alpha1, alpha2, and alpha3 genes, demonstrating that the complete conventional importin alpha gene family arose prior to the split between invertebrates and vertebrates. We have begun to analyze the genetic interactions among conventional importin alpha genes by studying their capacity to rescue the male and female sterility of importin alpha2 null flies. The sterility of alpha2 null males was rescued to similar extents by importin alpha1, alpha2, and alpha3 transgenes, suggesting that all three conventional importin alpha's are capable of performing the important role of importin alpha2 during spermatogenesis. In contrast, sterility of alpha2 null females was rescued only by importin alpha2 transgenes, suggesting that it plays a paralog-specific role in oogenesis. Female infertility was also rescued by a mutant importin alpha2 transgene lacking a site that is normally phosphorylated in ovaries. These rescue experiments suggest that male and female gametogenesis have distinct requirements for importin alpha2.}, } @article {pmid11989676, year = {2002}, author = {McShea, DW}, title = {A complexity drain on cells in the evolution of multicellularity.}, journal = {Evolution; international journal of organic evolution}, volume = {56}, number = {3}, pages = {441-452}, doi = {10.1111/j.0014-3820.2002.tb01357.x}, pmid = {11989676}, issn = {0014-3820}, mesh = {Animals ; *Biological Evolution ; *Cell Physiological Phenomena ; Models, Biological ; Rabbits ; Rats ; Trees/genetics ; }, abstract = {A hypothesis has been advanced recently predicting that, in evolution, as higher-level entities arise from associations of lower-level organisms, and as these entities acquire the ability to feed, reproduce, defend themselves, and so on, the lower-level organisms will tend to lose much of their internal complexity (McShea 2001a). In other words, in hierarchical transitions, there is a drain on numbers of part types at the lower level. One possible rationale is that the transfer of functional demands to the higher level renders many part types at the lower level useless, and thus their loss in evolution is favored by selection for economy. Here, a test is conducted at the cell level, comparing numbers of part types in free-living eukaryotic cells (protists) and the cells of metazoans and land plants. Differences are significant and consistent with the hypothesis, suggesting that tests at other hierarchical levels may be worthwhile.}, } @article {pmid11985014, year = {2002}, author = {Enmark, E and Gustafsson, JA}, title = {[Nuclear receptors in man, fly and worm provide greater understanding of disease].}, journal = {Lakartidningen}, volume = {99}, number = {11}, pages = {1186-1190}, pmid = {11985014}, issn = {0023-7205}, mesh = {Animals ; *Base Sequence ; Caenorhabditis elegans/genetics ; Drosophila melanogaster/genetics ; *Genetics, Medical ; Genomic Library ; Hominidae/genetics ; Humans ; Phylogeny ; Receptors, Cytoplasmic and Nuclear/*genetics ; Transcription Factors/*genetics ; }, abstract = {Recently the complete genomic sequences for three very different multicellular organisms have been published, from one nematode (Caenorhabditis elegans), one fly (Drosophila melanogaster) and human (Homo sapiens). Of course, this means a breakthrough in many ways for biological research. Summarised in this article are the findings made using these genomic sequences regarding the protein family of nuclear receptors. This is a group of transcription factors involved in many important biological processes, i.e. regulation of cholesterol homeostasis and fertility; classical members of this protein family are, amongst others, the receptors for estradiol and progesterone.}, } @article {pmid11983904, year = {2002}, author = {Lynch, M}, title = {Intron evolution as a population-genetic process.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {99}, number = {9}, pages = {6118-6123}, pmid = {11983904}, issn = {0027-8424}, support = {F32 GM020887/GM/NIGMS NIH HHS/United States ; GM20887/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Cell Division ; Exons ; *Genetics, Population ; *Introns ; *Models, Genetic ; Models, Statistical ; Mutation ; Recombination, Genetic ; }, abstract = {Debate over the mechanisms responsible for the phylogenetic and genomic distribution of introns has proceeded largely without consideration of the population-genetic forces influencing the establishment and retention of novel genetic elements. However, a simple model incorporating random genetic drift and weak mutation pressure against intron-containing alleles yields predictions consistent with a diversity of observations: (i) the rarity of introns in unicellular organisms with large population sizes, and their expansion after the origin of multicellular organisms with reduced population sizes; (ii) the relationship between intron abundance and the stringency of splice-site requirements; (iii) the tendency for introns to be more numerous and longer in regions of low recombination; and (iv) the bias toward phase-0 introns. This study provides a second example of a mechanism whereby genomic complexity originates passively as a "pathological" response to small population size, and raises difficulties for the idea that ancient introns played a major role in the origin of genes by exon shuffling.}, } @article {pmid11976967, year = {2002}, author = {Meiri, E and Levitan, A and Guo, F and Christopher, DA and Schaefer, D and Zrÿd, JP and Danon, A}, title = {Characterization of three PDI-like genes in Physcomitrella patens and construction of knock-out mutants.}, journal = {Molecular genetics and genomics : MGG}, volume = {267}, number = {2}, pages = {231-240}, doi = {10.1007/s00438-002-0658-5}, pmid = {11976967}, issn = {1617-4615}, mesh = {Amino Acid Sequence ; Base Sequence ; Bryopsida/enzymology/*genetics ; DNA, Complementary/genetics ; DNA, Plant/genetics ; Gene Targeting ; *Genes, Plant ; Molecular Sequence Data ; Mutagenesis, Insertional ; Phylogeny ; Protein Disulfide-Isomerases/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {Plant genomes typically contain several sequences homologous to protein disulfide isomerase (PDI). PDI was first identified as an abundant enzyme in the endoplasmic reticulum, where it catalyzes the formation, reduction, and isomerization of disulfide bonds during protein folding. PDI-like proteins have also been implicated in a variety of other functions, such as the regulation of cell adhesion, and may act as elicitors of the autoimmune response in mammals. A PDI-like protein (RB60) was recently shown to be imported into chloroplasts in the unicellular green alga Chlamydomonas reinhardtii and a higher plant, Pisum sativum, where it associates with thylakoid membranes. This suggests that the different PDI-like proteins in plant and animals may have diverse biological roles. To begin to elucidate the roles of PDI-like proteins, we have cloned, characterized, and generated knock-out mutants for three PDI-like genes that have high, medium, and low levels of expression, respectively, in the moss Physcomitrella patens. Phylogenetic analysis indicates that the three PDI-like proteins cluster with RB60 and four proteins from Arabidopsis thaliana. They are typified by an N-terminal domain rich in negatively charged residues. The knock-out mutants, which are the first knock-outs available for PDI-like proteins in a multicellular organism, were found to be viable, indicating that the function of each single gene is dispensable, and suggesting that they may be functionally complementary.}, } @article {pmid11967126, year = {2002}, author = {Stoorvogel, W and Kleijmeer, MJ and Geuze, HJ and Raposo, G}, title = {The biogenesis and functions of exosomes.}, journal = {Traffic (Copenhagen, Denmark)}, volume = {3}, number = {5}, pages = {321-330}, doi = {10.1034/j.1600-0854.2002.30502.x}, pmid = {11967126}, issn = {1398-9219}, mesh = {Antigen-Presenting Cells/physiology ; Cell Fusion ; Organelles/*physiology ; }, abstract = {Exosomes are membrane vesicles with a diameter of 40-100 nm that are secreted by many cell types into the extracellular milieu. They correspond to the internal vesicles of an endosomal compartment, the multivesicular body and are released upon exocytic fusion of this organelle with the plasma membrane. Intracellularly, they are formed by inward budding of the endosomal membrane in a process that sequesters particular proteins and lipids. The unique composition of exosomes may confer specific functions on them upon secretion. Although their physiological role in vivo is far from being unraveled, it is apparent that they function in a multitude of processes, including intercellular communication during the immune response. Exosomes may have evolved early in the evolution of multicellular organisms and also seem to be important for tissue developmental processes.}, } @article {pmid11965491, year = {2002}, author = {Ameisen, JC}, title = {On the origin, evolution, and nature of programmed cell death: a timeline of four billion years.}, journal = {Cell death and differentiation}, volume = {9}, number = {4}, pages = {367-393}, doi = {10.1038/sj.cdd.4400950}, pmid = {11965491}, issn = {1350-9047}, mesh = {Animals ; *Apoptosis ; *Biological Evolution ; Caenorhabditis elegans Proteins ; Caspases/physiology ; Eukaryota/cytology/physiology ; Eukaryotic Cells/physiology ; Homeodomain Proteins/physiology ; Humans ; Mitochondria/genetics/physiology ; Phylogeny ; Plant Physiological Phenomena ; Time ; }, abstract = {Programmed cell death is a genetically regulated process of cell suicide that is central to the development, homeostasis and integrity of multicellular organisms. Conversely, the dysregulation of mechanisms controlling cell suicide plays a role in the pathogenesis of a wide range of diseases. While great progress has been achieved in the unveiling of the molecular mechanisms of programmed cell death, a new level of complexity, with important therapeutic implications, has begun to emerge, suggesting (i) that several different self-destruction pathways may exist and operate in parallel in our cells, and (ii) that molecular effectors of cell suicide may also perform other functions unrelated to cell death induction and crucial to cell survival. In this review, I will argue that this new level of complexity, implying that there may be no such thing as a 'bona fide' genetic death program in our cells, might be better understood when considered in an evolutionary context. And a new view of the regulated cell suicide pathways emerges when one attempts to ask the question of when and how they may have become selected during evolution, at the level of ancestral single-celled organisms.}, } @article {pmid11956206, year = {2002}, author = {Sugiura, M and Kono, K and Liu, H and Shimizugawa, T and Minekura, H and Spiegel, S and Kohama, T}, title = {Ceramide kinase, a novel lipid kinase. Molecular cloning and functional characterization.}, journal = {The Journal of biological chemistry}, volume = {277}, number = {26}, pages = {23294-23300}, doi = {10.1074/jbc.M201535200}, pmid = {11956206}, issn = {0021-9258}, mesh = {Amino Acid Sequence ; Animals ; Blotting, Northern ; Cloning, Molecular ; Humans ; Mice ; Molecular Sequence Data ; Phosphotransferases (Alcohol Group Acceptor)/chemistry/*genetics/physiology ; Phylogeny ; Recombinant Proteins/biosynthesis/chemistry ; }, abstract = {Ceramide-1-phosphate is a sphingolipid metabolite that has been implicated in membrane fusion of brain synaptic vesicles and neutrophil phagolysosome formation. Ceramide-1-phosphate can be produced by ATP-dependent ceramide kinase activity, although little is known of this enzyme because it has not yet been highly purified or cloned. Based on sequence homology to sphingosine kinase type 1, we have now cloned a related lipid kinase, human ceramide kinase (hCERK). hCERK encodes a protein of 537 amino acids that has a catalytic region with a high degree of similarity to the diacylglycerol kinase catalytic domain. hCERK also has a putative N-myristoylation site on its NH(2) terminus followed by a pleckstrin homology domain. Membrane but not cytosolic fractions from HEK293 cells transiently transfected with a hCERK expression vector readily phosphorylated ceramide but not sphingosine or other sphingoid bases, diacylglycerol or phosphatidylinositol. This activity was clearly distinguished from those of bacterial or human diacylglycerol kinases. With natural ceramide as a substrate, the enzyme had a pH optimum of 6.0-7.5 and showed Michaelis-Menten kinetics, with K(m) values of 187 and 32 microm for ceramide and ATP, respectively. Northern blot analysis revealed that hCERK mRNA expression was high in the brain, heart, skeletal muscle, kidney, and liver. A BLAST search analysis using the hCERK sequence revealed that putative ceramide kinases (CERKs) exist widely in diverse multicellular organisms including plants, nematodes, insects, and vertebrates. Phylogenetic analysis revealed that CERKs are a new class of lipid kinases that are clearly distinct from sphingosine and diacylglycerol kinases. Cloning of CERK should provide new molecular tools to investigate the physiological functions of ceramide-1-phosphate.}, } @article {pmid11948623, year = {2002}, author = {Ceulemans, H and Stalmans, W and Bollen, M}, title = {Regulator-driven functional diversification of protein phosphatase-1 in eukaryotic evolution.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {24}, number = {4}, pages = {371-381}, doi = {10.1002/bies.10069}, pmid = {11948623}, issn = {0265-9247}, mesh = {Animals ; *Biological Evolution ; Eukaryotic Cells ; Genome ; Phosphoprotein Phosphatases/*genetics ; Phylogeny ; Protein Phosphatase 1 ; Vertebrates ; }, abstract = {We have used the (nearly) completed eukaryotic genome sequences to trace the evolution of thirteen families of established vertebrate regulators of type-1 protein phosphatases (PP1). Two of these families are present in all lineages of the eukaryotic crown and therefore qualify as candidate primordial regulators that determined the surface of PP1. The set of regulators of PP1 has continued to expand ever since, often in response to functional innovations in different eukaryotic lineages. In particular, the development of metazoan multicellularity was accompanied by an explosive increase in the number of regulators of PP1. The further increase in the functional diversity of PP1 in the vertebrate lineage was mainly achieved by the duplication of genes for regulatory subunits and by the conversion of already existing proteins into regulators of PP1. Unexpectedly, our analysis has also enabled us to classify nine poorly characterized proteins as likely regulators of PP1.}, } @article {pmid11932238, year = {2002}, author = {Galagan, JE and Nusbaum, C and Roy, A and Endrizzi, MG and Macdonald, P and FitzHugh, W and Calvo, S and Engels, R and Smirnov, S and Atnoor, D and Brown, A and Allen, N and Naylor, J and Stange-Thomann, N and DeArellano, K and Johnson, R and Linton, L and McEwan, P and McKernan, K and Talamas, J and Tirrell, A and Ye, W and Zimmer, A and Barber, RD and Cann, I and Graham, DE and Grahame, DA and Guss, AM and Hedderich, R and Ingram-Smith, C and Kuettner, HC and Krzycki, JA and Leigh, JA and Li, W and Liu, J and Mukhopadhyay, B and Reeve, JN and Smith, K and Springer, TA and Umayam, LA and White, O and White, RH and Conway de Macario, E and Ferry, JG and Jarrell, KF and Jing, H and Macario, AJ and Paulsen, I and Pritchett, M and Sowers, KR and Swanson, RV and Zinder, SH and Lander, E and Metcalf, WW and Birren, B}, title = {The genome of M. acetivorans reveals extensive metabolic and physiological diversity.}, journal = {Genome research}, volume = {12}, number = {4}, pages = {532-542}, pmid = {11932238}, issn = {1088-9051}, mesh = {Archaeal Proteins/genetics/physiology ; Carbon Monoxide/metabolism ; Cell Movement/genetics/physiology ; Euryarchaeota/metabolism ; Gene Expression Regulation, Archaeal/physiology ; *Genetic Variation ; *Genome, Archaeal ; Hydrogen/metabolism ; Membrane Proteins/genetics/physiology ; Methanosarcina/*genetics/physiology ; Molecular Sequence Data ; Multigene Family/genetics/physiology ; Nitrogen Fixation/genetics/physiology ; Oxygen/metabolism ; Polysaccharides/biosynthesis/genetics ; Protein Biosynthesis/physiology ; Replication Origin/genetics/physiology ; Signal Transduction/genetics/physiology ; Transcription, Genetic ; }, abstract = {Methanogenesis, the biological production of methane, plays a pivotal role in the global carbon cycle and contributes significantly to global warming. The majority of methane in nature is derived from acetate. Here we report the complete genome sequence of an acetate-utilizing methanogen, Methanosarcina acetivorans C2A. Methanosarcineae are the most metabolically diverse methanogens, thrive in a broad range of environments, and are unique among the Archaea in forming complex multicellular structures. This diversity is reflected in the genome of M. acetivorans. At 5,751,492 base pairs it is by far the largest known archaeal genome. The 4524 open reading frames code for a strikingly wide and unanticipated variety of metabolic and cellular capabilities. The presence of novel methyltransferases indicates the likelihood of undiscovered natural energy sources for methanogenesis, whereas the presence of single-subunit carbon monoxide dehydrogenases raises the possibility of nonmethanogenic growth. Although motility has not been observed in any Methanosarcineae, a flagellin gene cluster and two complete chemotaxis gene clusters were identified. The availability of genetic methods, coupled with its physiological and metabolic diversity, makes M. acetivorans a powerful model organism for the study of archaeal biology. [Sequence, data, annotations and analyses are available at http://www-genome.wi.mit.edu/.]}, } @article {pmid11925432, year = {2002}, author = {Bouché, N and Scharlat, A and Snedden, W and Bouchez, D and Fromm, H}, title = {A novel family of calmodulin-binding transcription activators in multicellular organisms.}, journal = {The Journal of biological chemistry}, volume = {277}, number = {24}, pages = {21851-21861}, doi = {10.1074/jbc.M200268200}, pmid = {11925432}, issn = {0021-9258}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Arabidopsis ; Caenorhabditis elegans ; Calmodulin/*chemistry/*metabolism ; Cell Line ; Cell Nucleus/metabolism ; Chromatography, Affinity ; Cloning, Molecular ; Conserved Sequence ; DNA/metabolism ; DNA, Complementary/metabolism ; Databases as Topic ; Dose-Response Relationship, Drug ; Drosophila ; Gene Library ; Glutathione Transferase/metabolism ; Humans ; Insecta ; Kinetics ; Models, Genetic ; Molecular Sequence Data ; Multigene Family ; Peptides/chemistry ; Phylogeny ; Protein Binding ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid ; Signal Transduction ; *Transcription, Genetic ; Transcriptional Activation ; Two-Hybrid System Techniques ; beta-Galactosidase/metabolism ; }, abstract = {Screening of cDNA expression libraries derived from plants exposed to stress, with 35S-labeled recombinant calmodulin as a probe, revealed a new family of proteins containing a transcription activation domain and two types of DNA-binding domains designated the CG-1 domain and the transcription factor immunoglobulin domain, ankyrin repeats, and a varying number of IQ calmodulin-binding motifs. Based on domain organization and amino acid sequence comparisons, similar proteins, with the same domain organization, were identified in the genomes of other multicellular organisms including human, Drosophila, and Caenorhabditis, whereas none were found in the complete genomes of single cell eukaryotes and prokaryotes. This family of proteins was designated calmodulin-binding transcription activators (CAMTAs). Arabidopsis thaliana contains six CAMTA genes (AtCAMTA1-AtCAMTA6). The transcription activation domain of AtCAMTA1 was mapped by testing a series of protein fusions with the DNA-binding domain of the bacterial LexA transcription factor and two reporter genes fused to LexA recognition sequences in yeast cells. Two human proteins designated HsCAMTA1 and HsCAMTA2 were also shown to activate transcription in yeast using the same reporter system. Subcellular fractionation of Arabidopsis tissues revealed the presence of CAMTAs predominantly in the nucleus. Calmodulin binding assays identified a region of 25 amino acids capable of binding calmodulin with high affinity (K(d) = 1.2 nm) in the presence of calcium. We suggest that CAMTAs comprise a conserved family of transcription factors in a wide range of multicellular eukaryotes, which possibly respond to calcium signaling by direct binding of calmodulin.}, } @article {pmid11923444, year = {2002}, author = {Jones, LL and Yamaguchi, Y and Stallcup, WB and Tuszynski, MH}, title = {NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {22}, number = {7}, pages = {2792-2803}, pmid = {11923444}, issn = {1529-2401}, support = {F32 NS010927/NS/NINDS NIH HHS/United States ; NS32717/NS/NINDS NIH HHS/United States ; R01NS37083/NS/NINDS NIH HHS/United States ; R01NS42291/NS/NINDS NIH HHS/United States ; R01 NS042291/NS/NINDS NIH HHS/United States ; NS10927/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Antigens/*metabolism ; Astrocytes/pathology ; Axons/metabolism/pathology ; Chondroitin Sulfate Proteoglycans/*metabolism ; Disease Progression ; Female ; Immunoblotting ; Immunohistochemistry ; Macrophages/*metabolism/pathology ; Microglia/pathology ; *Oligodendroglia/cytology ; Proteoglycans/*metabolism ; Rats ; Rats, Inbred F344 ; Silver Staining ; Spinal Cord Injuries/*metabolism/pathology ; Stem Cells/*metabolism/pathology ; }, abstract = {Several extracellular matrix (ECM) molecules have been identified as potent inhibitors of neurite outgrowth in vitro and are believed to limit axonal growth after CNS injury. Recent studies have shown that different members of the chondroitin sulfate proteoglycan (CSPG) class of putatively inhibitory ECM molecules are expressed after a number of CNS injuries. The purpose of this study was to evaluate the relative amounts of individual CSPGs expressed after spinal cord injury (SCI) and identify their cells of origin. Evaluation of total soluble CSPGs 2 weeks after dorsal column lesion in the rat demonstrated that NG2 is highly upregulated and is a major CSPG species. Immunocytochemical analysis further demonstrated that NG2 expression is upregulated within 24 hr of injury, peaks at 1 week, and remains elevated for at least an additional 7 weeks. NG2 expression results from a multicellular response to injury, including both reactive macrophages and oligodendrocyte progenitors; astrocytes were not identified as a major source of NG2. Immunocytochemical analysis of other CSPG family members 7 d after injury showed moderate upregulation of versican, brevican, and neurocan, and downregulation of phosphacan. Axonal tracing experiments demonstrated dense NG2 labeling adjacent to the forward processes of transected corticospinal tract axons in a spatial profile that could restrict axonal growth. Thus, NG2 is a major component of this putatively inhibitory class of ECM molecules expressed at sites of SCI and may restrict axonal regeneration.}, } @article {pmid11919151, year = {2002}, author = {Hubberstey, AV and Mottillo, EP}, title = {Cyclase-associated proteins: CAPacity for linking signal transduction and actin polymerization.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {16}, number = {6}, pages = {487-499}, doi = {10.1096/fj.01-0659rev}, pmid = {11919151}, issn = {1530-6860}, mesh = {Actin Cytoskeleton/*metabolism ; Actins/*metabolism ; Adaptor Proteins, Signal Transducing ; Adenylyl Cyclases/metabolism ; Amino Acid Sequence ; Animals ; Cell Cycle Proteins/chemistry/physiology ; *Cytoskeletal Proteins ; *Drosophila Proteins ; Evolution, Molecular ; Humans ; Microfilament Proteins/chemistry/genetics/*physiology ; Models, Biological ; Molecular Sequence Data ; Protein Structure, Tertiary ; *Saccharomyces cerevisiae Proteins ; Sequence Alignment ; *Signal Transduction ; }, abstract = {Many extracellular signals elicit changes in the actin cytoskeleton, which are mediated through an array of signaling proteins and pathways. One family of proteins that plays a role in regulating actin remodeling in response to cellular signals are the cyclase-associated proteins (CAPs). CAPs are highly conserved monomeric actin binding proteins present in a wide range of organisms including yeast, fly, plants, and mammals. The original CAP was isolated as a component of the Saccharomyces cerevisiae adenylyl cyclase complex that serves as an effector of Ras during nutritional signaling. CAPs are multifunctional molecules that contain domains involved in actin binding, adenylyl cyclase association in yeast, SH3 binding, and oligomerization. Genetic studies in yeast have implicated CAPs in vesicle trafficking and endocytosis. CAPs play a developmental role in multicellular organisms, and studies of Drosophila have illuminated the importance of the actin cytoskeleton during eye development and in establishing oocyte polarity. This review will highlight the critical structural and functional domains of CAPs, describe recent studies that have implied important roles for these proteins in linking cell signaling with actin polymerization, and highlight their roles in vesicle trafficking and development.}, } @article {pmid11893164, year = {2002}, author = {Hübner, K and Windoffer, R and Hutter, H and Leube, RE}, title = {Tetraspan vesicle membrane proteins: synthesis, subcellular localization, and functional properties.}, journal = {International review of cytology}, volume = {214}, number = {}, pages = {103-159}, doi = {10.1016/s0074-7696(02)14004-6}, pmid = {11893164}, issn = {0074-7696}, mesh = {Amino Acid Sequence ; Animals ; Biological Evolution ; Biological Transport/*physiology ; Endocytosis/physiology ; Exocytosis/physiology ; Humans ; Immunohistochemistry ; Membrane Proteins/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Multigene Family ; Protein Isoforms ; Protein Processing, Post-Translational ; Sequence Alignment ; Tissue Distribution ; Transport Vesicles/*chemistry/metabolism ; }, abstract = {Tetraspan vesicle membrane proteins (TVPs) are characterized by four transmembrane regions and cytoplasmically located end domains. They are ubiquitous and abundant components of vesicles in most, if not all, cells of multicellular organisms. TVP-containing vesicles shuttle between various membranous compartments and are localized in biosynthetic and endocytotic pathways. Based on gene organization and amino acid sequence similarities TVPs can be grouped into three distinct families that are referred to as physins, gyrins, and secretory carrier-associated membrane proteins (SCAMPs). In mammals synaptophysin, synaptoporin, pantophysin, and mitsugumin29 constitute the physins, synaptogyrin 1-4 the gyrins, and SCAMP1-5 the SCAMPs. Members of each family are cell-type-specifically synthesized resulting in unique patterns of TVP coexpression and subcellular colocalization. TVP orthologs have been identified in most multicellular organisms, including diverse animal and plant species, but have not been detected in unicellular organisms. They are subject to protein modification, most notably to phosphorylation, and are part of multimeric complexes. Experimental evidence is reviewed showing that TVPs contribute to vesicle trafficking and membrane morphogenesis.}, } @article {pmid11885497, year = {2002}, author = {Duan, Y and Seeman, E}, title = {Bone fragility in Asian and Caucasian men.}, journal = {Annals of the Academy of Medicine, Singapore}, volume = {31}, number = {1}, pages = {54-66}, pmid = {11885497}, issn = {0304-4602}, mesh = {Age Distribution ; Aged ; Aged, 80 and over ; Australia/epidemiology ; Bone Density/physiology ; Ethnicity/*genetics ; Female ; Fractures, Spontaneous/diagnosis/*ethnology ; Hip Fractures/diagnosis/ethnology ; Humans ; Incidence ; Male ; Middle Aged ; Osteoporosis/diagnosis/*ethnology ; Osteoporosis, Postmenopausal/diagnosis/epidemiology ; Risk Factors ; Sex Distribution ; Spinal Fractures/diagnosis/ethnology ; White People/*genetics ; }, abstract = {Hip and vertebral fractures are a public health problem in men of Asian and Caucasian origin. Inferences regarding gender and racial/ethnic differences in fracture rates must be made cautiously as problems in case ascertainment and classification of hip fractures, and problems in defining what constitutes a vertebral 'fracture' have not been solved. However, methodological issues probably do not entirely account for the heterogeneity of fracture patterns. There is likely to be a wide variation in fracture rates from country to country in Asia as reported in studies in Europe. The reasons for this heterogeneity are unknown. Caucasian men lose similar amounts of bone as Caucasian women during ageing from the endosteal surface of the bone. Net bone loss is less in men than women because men form more periosteal bone during ageing than do women. The extent of periosteal and endosteal bone modelling and remodelling have not been studied in Asian men and women. Nor have there been hypothesis-driven studies designed to compare periosteal apposition and endosteal bone loss in Asian males compared to Caucasian males. Sex hormone deficiencies contribute to abnormalities in skeletal size and mass during growth, remodelling imbalance and bone loss during ageing in men. The larger peak bone size and greater periosteal apposition with ageing in men compared to women is most likely to be androgen-dependent in Caucasians and Asians. Androgen deficiency may also partly account for reduced bone formation and negative bone balance at the basic multicellular unit (BMU). Oestrogen deficiency during growth is associated with reduced bone mass and increased leg length in males and females. Oestrogen deficiency during ageing may account for trabecular bone loss in men by increasing remodelling rate. There have been no anti-fracture efficacy studies done in Asian males. Studies on the pathophysiology of osteoporosis in males have given insight into the pathophysiology of osteoporosis in females. Similarly, collaborative research efforts between groups around the world will facilitate comparative studies in Asian and Caucasian communities. The results of this work will provide important insights into the pathophysiology of bone fragility in both groups.}, } @article {pmid11880641, year = {2002}, author = {Markmann-Mulisch, U and Hadi, MZ and Koepchen, K and Alonso, JC and Russo, VE and Schell, J and Reiss, B}, title = {The organization of Physcomitrella patensRAD51 genes is unique among eukaryotic organisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {99}, number = {5}, pages = {2959-2964}, pmid = {11880641}, issn = {0027-8424}, mesh = {Animals ; Base Sequence ; Bryopsida/*genetics ; DNA, Plant ; DNA-Binding Proteins/classification/*genetics ; Eukaryotic Cells ; Gene Expression ; Genes, Plant ; Humans ; Mice ; Molecular Sequence Data ; Phylogeny ; Rad51 Recombinase ; Sequence Homology, Nucleic Acid ; }, abstract = {Genetic recombination pathways and genes are well studied, but relatively little is known in plants, especially in lower plants. To study the recombination apparatus of a lower land plant, a recombination gene well characterized particularly in yeast, mouse, and man, the RAD51 gene, was isolated from the moss Physcomitrella patens and characterized. Two highly homologous RAD51 genes were found to be present. Duplicated RAD51 genes have been found thus far exclusively in eukaryotes with duplicated genomes. Therefore the presence of two highly homologous genes suggests a recent genome duplication event in the ancestry of Physcomitrella. Comparison of the protein sequences to Rad51 proteins from other organisms showed that both RAD51 genes originated within the group of plant Rad51 proteins. However, the two proteins form a separate clade in a phylogenetic tree of plant Rad51 proteins. In contrast to RAD51 genes from other multicellular eukaryotes, the Physcomitrella genes are not interrupted by introns. Because introns are a common feature of Physcomitrella genes, the lack of introns in the RAD51 genes is unusual and may indicate the presence of an unusual recombination apparatus in this organism. The presence of duplicated intronless RAD51 genes is unique among eukaryotes. Studies of further members of this lineage are needed to determine whether this feature may be typical of lower plants.}, } @article {pmid11867702, year = {2002}, author = {Schröder, J and Kautz, K and Wernicke, W}, title = {Gamma-tubulin in barley and tobacco: sequence relationship and RNA expression patterns in developing leaves during mitosis and post-mitotic growth.}, journal = {Plant & cell physiology}, volume = {43}, number = {2}, pages = {224-229}, doi = {10.1093/pcp/pcf030}, pmid = {11867702}, issn = {0032-0781}, mesh = {Amino Acid Sequence ; Blotting, Northern ; DNA, Complementary/genetics/isolation & purification ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Hordeum/*genetics/growth & development ; Mitosis/genetics ; Molecular Sequence Data ; Phylogeny ; Plant Leaves/*genetics/growth & development ; RNA, Plant/genetics/metabolism ; Sequence Homology, Amino Acid ; Tobacco/*genetics/growth & development ; Tubulin/biosynthesis/*genetics ; }, abstract = {gamma-Tubulin is typically associated with microtubule organising centres, such as the centrosome, and appears to mediate microtubule nucleation. Centrosomes are usually not found in higher plants, but active genes homologous to gamma-tubulin have been identified in the plant kingdom, including the angiosperms Arabidopsis, maize and rice. We have isolated and characterised gamma-tubulin cDNA sequences of two further angiosperm species, barley and tobacco. Sequence comparison revealed a phylogenetic tree with distinct clusters corresponding to the systematic position of the species. Furthermore, domains, thought to be exposed in the folded protein and to be candidates for interaction with associated, nucleation-site related proteins, exhibited motifs highly specific of multicellular plants. Strong expression of the gamma-tubulin genes, as determined by Northern blotting, correlated with mitotic activity. Expression dropped distinctly when mitotic activity ceased. Thus, in post-mitotic tissues that showed intricate reshuffling of cortical microtubule arrays related to cell shaping only very low gamma-tubulin steady-state RNA levels were found, contrasting with the situation for alpha-tubulin. The findings indicate that gamma-tubulin expression in plants may be more tightly linked to mitosis, although there is some gamma-tubulin expression at the RNA level even after mitosis. It follows that the post-mitotic changes in microtubular arrays may be less dependent on concurrent gamma-tubulin RNA expression than mitotic cells.}, } @article {pmid11861608, year = {2002}, author = {Srivastava, P}, title = {Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses.}, journal = {Annual review of immunology}, volume = {20}, number = {}, pages = {395-425}, doi = {10.1146/annurev.immunol.20.100301.064801}, pmid = {11861608}, issn = {0732-0582}, mesh = {Adaptation, Physiological ; Animals ; Antigen-Presenting Cells/*immunology ; Antigens, CD/metabolism ; Biological Evolution ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Heat-Shock Proteins/chemistry/*immunology ; Humans ; Immunity, Innate ; Major Histocompatibility Complex ; Mice ; Models, Immunological ; Molecular Chaperones/immunology ; Peptides/*immunology ; }, abstract = {Heat shock proteins are abundant soluble intracellular proteins, present in all cells. Members of the heat shock protein family bind peptides including antigenic peptides generated within cells. Heat shock proteins also interact with antigen presenting cells through CD91 and other receptors, eliciting a cascade of events including re-presentation of heat shock protein-chaperoned peptides by MHC, translocation of NF kappa B into the nuclei and maturation of dendritic cells. These consequences point to a key role of heat shock proteins in fundamental immunological phenomena such as activation of antigen presenting cells, indirect presentation (or cross-priming), and chaperoning of peptides during antigen presentation. Heat shock proteins appear to have been involved in innate immune responses since the emergence of phagocytes in early multicellular organisms and to have been commandeered for adaptive immune responses with the advent of specificity. These properties of heat shock proteins also allow them to be used for immunotherapy of cancers and infections in novel ways.}, } @article {pmid11859360, year = {2002}, author = {Wood, V and Gwilliam, R and Rajandream, MA and Lyne, M and Lyne, R and Stewart, A and Sgouros, J and Peat, N and Hayles, J and Baker, S and Basham, D and Bowman, S and Brooks, K and Brown, D and Brown, S and Chillingworth, T and Churcher, C and Collins, M and Connor, R and Cronin, A and Davis, P and Feltwell, T and Fraser, A and Gentles, S and Goble, A and Hamlin, N and Harris, D and Hidalgo, J and Hodgson, G and Holroyd, S and Hornsby, T and Howarth, S and Huckle, EJ and Hunt, S and Jagels, K and James, K and Jones, L and Jones, M and Leather, S and McDonald, S and McLean, J and Mooney, P and Moule, S and Mungall, K and Murphy, L and Niblett, D and Odell, C and Oliver, K and O'Neil, S and Pearson, D and Quail, MA and Rabbinowitsch, E and Rutherford, K and Rutter, S and Saunders, D and Seeger, K and Sharp, S and Skelton, J and Simmonds, M and Squares, R and Squares, S and Stevens, K and Taylor, K and Taylor, RG and Tivey, A and Walsh, S and Warren, T and Whitehead, S and Woodward, J and Volckaert, G and Aert, R and Robben, J and Grymonprez, B and Weltjens, I and Vanstreels, E and Rieger, M and Schäfer, M and Müller-Auer, S and Gabel, C and Fuchs, M and Düsterhöft, A and Fritzc, C and Holzer, E and Moestl, D and Hilbert, H and Borzym, K and Langer, I and Beck, A and Lehrach, H and Reinhardt, R and Pohl, TM and Eger, P and Zimmermann, W and Wedler, H and Wambutt, R and Purnelle, B and Goffeau, A and Cadieu, E and Dréano, S and Gloux, S and Lelaure, V and Mottier, S and Galibert, F and Aves, SJ and Xiang, Z and Hunt, C and Moore, K and Hurst, SM and Lucas, M and Rochet, M and Gaillardin, C and Tallada, VA and Garzon, A and Thode, G and Daga, RR and Cruzado, L and Jimenez, J and Sánchez, M and del Rey, F and Benito, J and Domínguez, A and Revuelta, JL and Moreno, S and Armstrong, J and Forsburg, SL and Cerutti, L and Lowe, T and McCombie, WR and Paulsen, I and Potashkin, J and Shpakovski, GV and Ussery, D and Barrell, BG and Nurse, P}, title = {The genome sequence of Schizosaccharomyces pombe.}, journal = {Nature}, volume = {415}, number = {6874}, pages = {871-880}, doi = {10.1038/nature724}, pmid = {11859360}, issn = {0028-0836}, mesh = {Base Sequence ; Centromere ; Chromosome Mapping ; Chromosomes, Fungal ; DNA, Fungal ; Eukaryotic Cells ; Fungal Proteins/chemistry/genetics ; Gene Duplication ; Genetic Diseases, Inborn ; *Genome, Fungal ; Humans ; Introns ; Protein Structure, Tertiary ; Schizosaccharomyces/*genetics ; Sequence Analysis, DNA ; }, abstract = {We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.}, } @article {pmid11854508, year = {2002}, author = {Schutte, BC and Mitros, JP and Bartlett, JA and Walters, JD and Jia, HP and Welsh, MJ and Casavant, TL and McCray, PB}, title = {Discovery of five conserved beta -defensin gene clusters using a computational search strategy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {99}, number = {4}, pages = {2129-2133}, pmid = {11854508}, issn = {0027-8424}, support = {P30-HD27748/HD/NICHD NIH HHS/United States ; CA-85188/CA/NCI NIH HHS/United States ; HL-61234/HL/NHLBI NIH HHS/United States ; K12 HD027748/HD/NICHD NIH HHS/United States ; P50 HL061234/HL/NHLBI NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Computers ; Conserved Sequence ; Contig Mapping ; Cysteine/chemistry ; Exons ; Humans ; Markov Chains ; Mice ; Models, Genetic ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Sequence Homology, Amino Acid ; Software ; beta-Defensins/*chemistry/*genetics ; }, abstract = {The innate immune system includes antimicrobial peptides that protect multicellular organisms from a diverse spectrum of microorganisms. beta-Defensins comprise one important family of mammalian antimicrobial peptides. The annotation of the human genome fails to reveal the expected diversity, and a recent query of the draft sequence with the blast search engine found only one new beta-defensin gene (DEFB3). To define better the beta-defensin gene family, we adopted a genomics approach that uses hmmer, a computational search tool based on hidden Markov models, in combination with blast. This strategy identified 28 new human and 43 new mouse beta-defensin genes in five syntenic chromosomal regions. Within each syntenic cluster, the gene sequences and organization were similar, suggesting each cluster pair arose from a common ancestor and was retained because of conserved functions. Preliminary analysis indicates that at least 26 of the predicted genes are transcribed. These results demonstrate the value of a genomewide search strategy to identify genes with conserved structural motifs. Discovery of these genes represents a new starting point for exploring the role of beta-defensins in innate immunity.}, } @article {pmid11850067, year = {2002}, author = {Jin, C and Jin, Y and Wennerberg, J and Akervall, J and Dictor, M and Mertens, F}, title = {Karyotypic heterogeneity and clonal evolution in squamous cell carcinomas of the head and neck.}, journal = {Cancer genetics and cytogenetics}, volume = {132}, number = {2}, pages = {85-96}, doi = {10.1016/s0165-4608(01)00535-0}, pmid = {11850067}, issn = {0165-4608}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell/*genetics ; Female ; Genetic Heterogeneity ; Head and Neck Neoplasms/*genetics ; Humans ; Karyotyping ; Likelihood Functions ; Male ; Middle Aged ; }, abstract = {Head and neck squamous cell carcinomas (HNSCC) are often characterized by complex karyotypic changes, and a substantial proportion of the reported tumors have shown intratumor heterogeneity in the form of cytogenetically related (40%) or unrelated clones (20%). In order to study intratumor heterogeneity and to distinguish the temporal order of chromosome rearrangements in these tumors, two or more samples from different areas of the same tumor were separately examined in 19 HNSCC, yielding karyotypes from a total of 42 tumor samples. Intrasample heterogeneity was observed in 16 samples. Two samples displayed both related and unrelated multiple clones, four samples showed only multiple unrelated clones, and the remaining 10 samples had only related subclones. Intersample heterogeneity was detected in all but one tumor. Five tumors showed both cytogenetically related and unrelated multiple clones, 11 were found to have only related subclones, and the remaining two tumors showed only unrelated clones. Clonal evolution could be assessed in 13 tumors. A comparison of chromosome imbalances in different subclones from these tumors suggests that partial or entire loss of 3p, 8p, 9p, and 18q and gain of genetic material from 3q and 8q are likely to be early genetic events. In contrast, loss of 1q, 6p, 7q, and chromosome 10, as well as gain of chromosome arms 5p and 7p, are most probably later genetic events. One of the examined tumors contained two highly complex clones that were cytogenetically unrelated, indicating that this tumor had a multicellular origin.}, } @article {pmid11849977, year = {2002}, author = {Rozema, J and Björn, LO and Bornman, JF and Gaberscik, A and Häder, DP and Trost, T and Germ, M and Klisch, M and Gröniger, A and Sinha, RP and Lebert, M and He, YY and Buffoni-Hall, R and de Bakker, NV and van de Staaij, J and Meijkamp, BB}, title = {The role of UV-B radiation in aquatic and terrestrial ecosystems--an experimental and functional analysis of the evolution of UV-absorbing compounds.}, journal = {Journal of photochemistry and photobiology. B, Biology}, volume = {66}, number = {1}, pages = {2-12}, doi = {10.1016/s1011-1344(01)00269-x}, pmid = {11849977}, issn = {1011-1344}, mesh = {Biological Evolution ; DNA Damage/radiation effects ; DNA Repair/radiation effects ; DNA, Plant/*radiation effects ; Ecosystem ; *Flavonoids ; *Kaempferols ; Molecular Conformation ; Plants/chemistry/genetics/metabolism/*radiation effects ; Quercetin/*analogs & derivatives/metabolism ; Temperature ; *Ultraviolet Rays ; }, abstract = {We analysed and compared the functioning of UV-B screening pigments in plants from marine, fresh water and terrestrial ecosystems, along the evolutionary line of cyanobacteria, unicellular algae, primitive multicellular algae, charophycean algae, lichens, mosses and higher plants, including amphibious macrophytes. Lichens were also included in the study. We were interested in the following key aspects: (a) does the water column function effectively as an 'external UV-B filter'?; (b) do aquatic plants need less 'internal UV-B screening' than terrestrial plants?; (c) what role does UV screening play in protecting the various plant groups from UV-B damage, such as the formation of thymine dimers?; and (d) since early land 'plants' (such as the predecessors of present-day cyanobacteria, lichens and mosses) experienced higher UV-B fluxes than higher plants, which evolved later, are primitive aquatic and land organisms (cyanobacteria, algae, lichens, mosses) better adapted to present-day levels of UV-B than higher plants? Furthermore, polychromatic action spectra for the induction of UV screening pigments of aquatic organisms have been determined. This is relevant for translating 'physical' radiation measurements of solar UV-B into 'biological' and 'ecological' effects. From the action spectra, radiation amplification factors (RAFs) have been calculated. These action spectra allow us to determine any mitigating or antagonistic effects in the ecosystems and therefore qualify the damage prediction for the ecosystems under study. We summarize and discuss the main results based on three years of research of four European research groups. The central theme of the work was the investigation of the effectiveness of the various screening compounds from the different species studied in order to gain some perspective of the evolutionary adaptations from lower to higher plant forms. The induction of mycosporine-like amino acids (MAAs) was studied in the marine dinoflagellate Gyrodinium dorsum, the green algal species Prasiola stipitata and in the cyanobacterium Anabaena sp. While visible (400-700 nm) and long wavelength UV-A (315-400 nm) showed only a slight effect, MAAs were effectively induced by UV-B (280-315 nm). The growth of the lower land organisms studied, i.e. the lichens Cladina portentosa, Cladina foliacaea and Cladonia arbuscula, and the club moss Lycopodiumannotinum, was not significantly reduced when grown under elevated UV-B radiation (simulating 15% ozone depletion). The growth in length of the moss Tortula ruralis was reduced under elevated UV-B. Of the aquatic plants investigated the charophytes Chara aspera showed decreased longitudinal growth under elevated UV-B. In the 'aquatic higher plants' studied, Ceratophyllum demersum, Batrachium trichophyllum and Potamogeton alpinus, there was no such depressed growth with enhanced UV-B. In Chara aspera, neither MAAs nor flavonoids could be detected. Of the terrestrial higher plants studied, Fagopyrum esculentum, Deschampsia antarctica, Vicia faba, Calamagrostis epigejos and Carex arenaria, the growth of the first species was depressed with enhanced UV-B, in the second species length growth was decreased, but the shoot number was increased, and in the latter two species of a dune grassland there was no reduced growth with enhanced UV-B. In the dune grassland species studied outdoors, at least five different flavonoids appeared in shoot tissue. Some of the flavonoids in the monocot species, which were identified and quantified with HPLC, included orientin, luteolin, tricin and apigenin. A greenhouse study with Vicia faba showed that two flavonoids (aglycones) respond particularly to enhanced UV-B. Of these, quercetin is UV-B inducible and mainly located in epidermal cells, while kaempferol occurs constitutively. In addition to its UV-screening function, quercetin may also act as an antioxidant. Polychromatic action spectra were determined for induction of the UV-absorbing pigments in three photosynthetic organisms, representing very different taxonomic groups and different habitats. In ultraviolet photobiology, action spectra mainly serve two purposes: (1) identification of the molecular species involved in light absorption; and (2) calculation of radiation amplification factors for assessing the effect of ozone depletion. Radiation amplification factors (RAFs) were calculated from the action spectra. In a somewhat simplified way, RAF can be defined as the percent increase of radiation damage for a 1% depletion of the ozone layer. Central European summer conditions were used in the calculations, but it has been shown that RAF values are not critically dependent on latitude or season. If only the ultraviolet spectral region is considered, the RAF values obtained are 0.7 for the green alga Prasiola stipitata, 0.4 for the dinoflagellate Gyrodinium dorsum, and 1.0 for the cyanobacterium Anabaena sp. In the case of P. stipitata, however, the effect of visible light (PAR, photosynthetically active radiation, 400-700 nm) is sufficient to lower the RAF to about 0.4, while the PAR effect for G. dorsum is negligible. RAFs for some damage processes, such as for DNA damage (RAF=2.1 if protective effects or photorepair are not considered [1]), are higher than those above. Our interpretation of this is that if the ozone layer is depleted, increased damaging radiation could overrule increased synthesis of protective pigments. In addition to investigating the functional effectiveness of the different screening compounds, direct UV effects on a number of key processes were also studied in order to gain further insight into the ability of the organisms to withstand enhanced UV-B radiation. To this end, the temperature-dependent repair of cyclobutane dimers (CPD) and (6-4) photoproducts induced by enhanced UV-B was studied in Nicotiana tabacum, and the UV-B induction of CPD was studied in the lichen Cladonia arbuscula. Also, photosynthesis and motility were monitored and the response related to the potential function of the screening compounds of the specific organism.}, } @article {pmid11846602, year = {2002}, author = {Plotkin, JB and Nowak, MA}, title = {The different effects of apoptosis and DNA repair on tumorigenesis.}, journal = {Journal of theoretical biology}, volume = {214}, number = {3}, pages = {453-467}, doi = {10.1006/jtbi.2001.2471}, pmid = {11846602}, issn = {0022-5193}, mesh = {Animals ; Apoptosis/*genetics ; Cells/*pathology ; DNA Repair/*genetics ; Humans ; *Markov Chains ; Mutation ; Neoplasms/*pathology ; Time Factors ; }, abstract = {Complex multicellular organisms have evolved mechanisms to ensure that individual cells follow their proper developmental and somatic programs. Tumorigenesis, or uncontrolled cellular proliferation, is caused by somatic mutations to those genetic constraints that normally operate within a tissue. Genes involved in DNA repair and apoptosis are particularly instrumental in safeguarding cells against tumorigenesis. In this paper, we introduce a stochastic framework to analyse the somatic evolution of cancer initiation. Within this model, we study how apoptosis and DNA repair can maintain the transient stability of somatic cells and delay the onset of cancer. Focusing on individual cell lineages, we calculate the waiting time before tumorigenesis in the presence of varying degrees of apoptosis and DNA repair. We find that the loss of DNA repair or the loss of apoptosis both hasten tumorigenesis, but in characteristically different ways.}, } @article {pmid11837302, year = {2002}, author = {Hanada, S and Takaichi, S and Matsuura, K and Nakamura, K}, title = {Roseiflexus castenholzii gen. nov., sp. nov., a thermophilic, filamentous, photosynthetic bacterium that lacks chlorosomes.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {52}, number = {Pt 1}, pages = {187-193}, doi = {10.1099/00207713-52-1-187}, pmid = {11837302}, issn = {1466-5026}, mesh = {Bacteriochlorophylls/metabolism ; Carotenoids/metabolism ; Chlorobi/*classification/genetics/*physiology/ultrastructure ; DNA, Ribosomal/analysis ; Fresh Water/microbiology ; Light-Harvesting Protein Complexes ; Molecular Sequence Data ; *Photosynthesis ; Photosynthetic Reaction Center Complex Proteins/metabolism ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Temperature ; }, abstract = {A novel thermophilic, photosynthetic bacterium, designated strain HLO8T, was isolated from a bacterial mat in a Japanese hot spring. Morphologically, the isolate was an unbranched multicellular filament with a cell diameter of 0.8-1.0 microm. The bacterium was red to reddish-brown in colour and formed a distinct red bacterial mat in the natural environment. It was able to grow photoheterotrophically under anaerobic light conditions and also chemoheterotrophically under aerobic dark conditions. Optimal growth occurred at 50 degrees C and pH 7.5-8.0. The cells contained bacteriochlorophyll (Bchl) a and gamma-carotene derivatives as photosynthetic pigments, but lacked Bchl c and chlorosomes. Cellular fatty acids in the isolate were mainly C16:0, C14:0 and C15:0. The major quinone was menaquinone-11. The DNA G+C content was 62.0 mol% (by HPLC). Phylogenetic analysis based on 16S rDNA sequencing suggested that the isolate belonged to the anoxygenic filamentous phototrophic bacteria represented by Chloroflexus aurantiacus, but was clearly distant from all members in this group (the sequence similarities between the isolate and its relatives were less than 83.8%). Based on genotypic and phenotypic data, the name Roseiflexus castenholzii gen. nov., sp. nov. is proposed for this isolate; the type strain is HLO8T (= DSM 13941T = JCM 11240T).}, } @article {pmid11825887, year = {2002}, author = {Chambergo, FS and Bonaccorsi, ED and Ferreira, AJ and Ramos, AS and Ferreira Júnior, JR and Abrahão-Neto, J and Farah, JP and El-Dorry, H}, title = {Elucidation of the metabolic fate of glucose in the filamentous fungus Trichoderma reesei using expressed sequence tag (EST) analysis and cDNA microarrays.}, journal = {The Journal of biological chemistry}, volume = {277}, number = {16}, pages = {13983-13988}, doi = {10.1074/jbc.M107651200}, pmid = {11825887}, issn = {0021-9258}, mesh = {Acetates/metabolism ; Cell Nucleus/metabolism ; Citric Acid Cycle ; DNA, Complementary/metabolism ; Dose-Response Relationship, Drug ; Ethanol/metabolism ; *Expressed Sequence Tags ; Gene Library ; Glucose/*metabolism/pharmacology ; Models, Biological ; Molecular Sequence Data ; NAD/metabolism ; *Oligonucleotide Array Sequence Analysis ; Oxygen/metabolism ; RNA, Messenger/metabolism ; Sequence Analysis, DNA ; Time Factors ; Trichoderma/*metabolism ; }, abstract = {Despite the intense interest in the metabolic regulation and evolution of the ATP-producing pathways, the long standing question of why most multicellular microorganisms metabolize glucose by respiration rather than fermentation remains unanswered. One such microorganism is the cellulolytic fungus Trichoderma reesei (Hypocrea jecorina). Using EST analysis and cDNA microarrays, we find that in T. reesei expression of the genes encoding the enzymes of the tricarboxylic acid cycle and the proteins of the electron transport chain is programmed in a way that favors the oxidation of pyruvate via the tricarboxylic acid cycle rather than its reduction to ethanol by fermentation. Moreover, the results indicate that acetaldehyde may be channeled into acetate rather than ethanol, thus preventing the regeneration of NAD(+), a pivotal product required for anaerobic metabolism. The studies also point out that the regulatory machinery controlled by glucose was most probably the target of evolutionary pressure that directed the flow of metabolites into respiratory metabolism rather than fermentation. This finding has significant implications for the development of metabolically engineered cellulolytic microorganisms for fuel production from cellulose biomass.}, } @article {pmid11818563, year = {2002}, author = {Krakauer, DC and Plotkin, JB}, title = {Redundancy, antiredundancy, and the robustness of genomes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {99}, number = {3}, pages = {1405-1409}, pmid = {11818563}, issn = {0027-8424}, mesh = {*Biological Evolution ; *Genome ; *Models, Genetic ; Selection, Genetic ; }, abstract = {Genetic mutations that lead to undetectable or minimal changes in phenotypes are said to reveal redundant functions. Redundancy is common among phenotypes of higher organisms that experience low mutation rates and small population sizes. Redundancy is less common among organisms with high mutation rates and large populations, or among the rapidly dividing cells of multicellular organisms. In these cases, one even observes the opposite tendency: a hypersensitivity to mutation, which we refer to as antiredundancy. In this paper we analyze the evolutionary dynamics of redundancy and antiredundancy. Assuming a cost of redundancy, we find that large populations will evolve antiredundant mechanisms for removing mutants and thereby bolster the robustness of wild-type genomes; whereas small populations will evolve redundancy to ensure that all individuals have a high chance of survival. We propose that antiredundancy is as important for developmental robustness as redundancy, and is an essential mechanism for ensuring tissue-level stability in complex multicellular organisms. We suggest that antiredundancy deserves greater attention in relation to cancer, mitochondrial disease, and virus infection.}, } @article {pmid11809832, year = {2002}, author = {Vartiainen, MK and Mustonen, T and Mattila, PK and Ojala, PJ and Thesleff, I and Partanen, J and Lappalainen, P}, title = {The three mouse actin-depolymerizing factor/cofilins evolved to fulfill cell-type-specific requirements for actin dynamics.}, journal = {Molecular biology of the cell}, volume = {13}, number = {1}, pages = {183-194}, pmid = {11809832}, issn = {1059-1524}, mesh = {Actin Depolymerizing Factors ; Actins/chemistry/genetics/*metabolism ; Amino Acid Sequence ; Animals ; Cofilin 1 ; Cofilin 2 ; Destrin ; Endothelium/metabolism ; Epithelial Cells/metabolism ; Evolution, Molecular ; Fluorescent Antibody Technique ; HeLa Cells ; Humans ; In Situ Hybridization ; Male ; Mice/embryology/*genetics/metabolism ; Microfilament Proteins/chemistry/genetics/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Muscle, Skeletal/metabolism ; Phylogeny ; Protein Isoforms/chemistry/genetics/metabolism ; Protein Structure, Secondary ; Sequence Alignment ; Tissue Distribution ; }, abstract = {Actin-depolymerizing factor (ADF)/cofilins are essential regulators of actin filament turnover. Several ADF/cofilin isoforms are found in multicellular organisms, but their biological differences have remained unclear. Herein, we show that three ADF/cofilins exist in mouse and most likely in all other mammalian species. Northern blot and in situ hybridization analyses demonstrate that cofilin-1 is expressed in most cell types of embryos and adult mice. Cofilin-2 is expressed in muscle cells and ADF is restricted to epithelia and endothelia. Although the three mouse ADF/cofilins do not show actin isoform specificity, they all depolymerize platelet actin filaments more efficiently than muscle actin. Furthermore, these ADF/cofilins are biochemically different. The epithelial-specific ADF is the most efficient in turning over actin filaments and promotes a stronger pH-dependent actin filament disassembly than the two other isoforms. The muscle-specific cofilin-2 has a weaker actin filament depolymerization activity and displays a 5-10-fold higher affinity for ATP-actin monomers than cofilin-1 and ADF. In steady-state assays, cofilin-2 also promotes filament assembly rather than disassembly. Taken together, these data suggest that the three biochemically distinct mammalian ADF/cofilin isoforms evolved to fulfill specific requirements for actin filament dynamics in different cell types.}, } @article {pmid11800396, year = {2001}, author = {Horling, F and Baier, M and Dietz, KJ}, title = {Redox-regulation of the expression of the peroxide-detoxifying chloroplast 2-cys peroxiredoxin in the liverwort Riccia fluitans.}, journal = {Planta}, volume = {214}, number = {2}, pages = {304-313}, doi = {10.1007/s004250100623}, pmid = {11800396}, issn = {0032-0935}, mesh = {Amino Acid Sequence ; Arabidopsis Proteins ; Ascorbic Acid/pharmacology ; Blotting, Western ; Chloroplasts/metabolism ; Cloning, Molecular ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Glutathione/pharmacology ; Molecular Sequence Data ; Oxidation-Reduction ; Peroxidases/genetics/*metabolism ; Peroxiredoxins ; Phylogeny ; Plant Proteins/genetics/metabolism ; Plants/drug effects/genetics/*metabolism ; Sequence Homology, Amino Acid ; Signal Transduction ; }, abstract = {2-Cys peroxiredoxins (2-CPs) are H2O2- and alkyl hydroperoxide-detoxifying enzymes, and occur in animals, fungi, bacteria and higher plants. Here, the cDNA encoding a peroxiredoxin of a multicellular cryptogamic plant was first cloned from the liverwort Riccia fluitans L., and the dependence of its expression on the cellular redox state was analysed. The presence of an N-terminal targeting signal indicates that, like 2-CPs from higher plants, Riccia 2-CP is posttranslationally imported into chloroplasts. Addition of ascorbate and other reductants suppressed 2-CP gene expression and decreased 2-CP protein levels. With ascorbate, the decrease in 2-CP transcript level was fast, concentration dependent, and correlated with the amounts of ascorbate taken up by the tissue. In an approach to identify signaling components, staurosporine was proved to be a highly potent inhibitor of ascorbate-dependent repression of 2-CP-expression. The staurosporine effect indicates that a serine/threonine-kinase is involved in ascorbate-modulated redox regulation of 2-CP expression.}, } @article {pmid11792557, year = {2002}, author = {Parfitt, AM}, title = {Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression.}, journal = {Bone}, volume = {30}, number = {1}, pages = {5-7}, doi = {10.1016/s8756-3282(01)00642-1}, pmid = {11792557}, issn = {8756-3282}, mesh = {Animals ; Biomechanical Phenomena ; Bone Remodeling/*physiology ; Bone Resorption/physiopathology ; Bone and Bones/metabolism ; Humans ; Osteoblasts/physiology ; Osteoclasts/physiology ; }, } @article {pmid11790259, year = {2001}, author = {Zientz, E and Silva, FJ and Gross, R}, title = {Genome interdependence in insect-bacterium symbioses.}, journal = {Genome biology}, volume = {2}, number = {12}, pages = {REVIEWS1032}, pmid = {11790259}, issn = {1474-760X}, mesh = {Animals ; Bacterial Physiological Phenomena ; Buchnera/genetics/physiology ; *Genome, Bacterial ; Host-Parasite Interactions ; Insecta/*microbiology/physiology ; Models, Biological ; Oligonucleotide Array Sequence Analysis ; Phylogeny ; Symbiosis ; }, abstract = {Symbioses between unicellular and multicellular organisms have contributed significantly to the evolution of life on Earth. As exemplified by several studies of bacterium-insect symbioses, modern genomic techniques are providing exciting new information about the molecular basis and the biological roles of these complex relationships, revealing for instance that symbionts have lost many genes for functions that are provided by the host, but that they can provide amino acids that the host cannot synthesize.}, } @article {pmid11782943, year = {2002}, author = {Miller, SM}, title = {Taming the fierce roller: an "enhanced" understanding of cellular differentiation in Volvox.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {24}, number = {1}, pages = {3-7}, doi = {10.1002/bies.10029}, pmid = {11782943}, issn = {0265-9247}, mesh = {Algal Proteins/*genetics/metabolism ; Cell Differentiation ; Chlorophyta/cytology/genetics/*physiology ; *Gene Expression Regulation ; Models, Genetic ; Regulatory Sequences, Nucleic Acid/physiology ; }, abstract = {Few organisms offer a better opportunity to explore the mechanisms of cellular differentiation, and their origins, than Volvox. Volvox consists of just two cell types, germ and soma, and is the most complex member of a family of green algae that includes unicellular and multicellular relatives. At the heart of the cell-fate determination program of Volvox carteri is the regA gene, which encodes a putative transcriptional repressor that prevents somatic cells from expressing reproductive functions. Stark et al. have dissected the regA gene to determine how its expression is restricted to somatic cells. Their results suggest that regA expression is controlled by multiple enhancers, the most important of which prevents transcription in reproductive cells. While these findings shed light on Volvox development, they also raise a new set of questions about the mechanisms that control the germ-soma dichotomy in this organism.}, } @article {pmid11769123, year = {2001}, author = {Galitskiĭ, VA}, title = {[Cell determination and differentiation: a concept of gene clusters].}, journal = {Tsitologiia}, volume = {43}, number = {10}, pages = {913-925}, pmid = {11769123}, issn = {0041-3771}, mesh = {Animals ; Biological Evolution ; Cell Differentiation/*genetics ; Cell Lineage/*genetics ; *Gene Expression Regulation, Developmental ; Humans ; *Multigene Family ; Stem Cells/cytology/physiology ; }, abstract = {This paper formulates a conception of cluster organization of the genetic material, responsible for cell determination and differentiation in multicellular organisms. According to this conception, gene controlling each particular stage of these processes are functionally integrated via genes-activators into gene groups (clusters) of different levels of hierarchy. Besides, some hypotheses of molecular mechanisms providing the action of these gene groups have been put forward. Attempts were made to elucidate some phenomena of cell differentiation, specifically a drop or a complete loss of dividing ability in highly specialized cells, in addition to a property of the cell to remember the history of its own development inside the organism, and to inherit the ancestor's direction of differentiation. Attention was paid to a mechanism (originating from this conception) of the emergency of malignant tumors, which means that cells giving rise to tumors are known to evade primarily their involvement in the process of further specialization. Besides, mechanisms of a molecular supply of positional information are examined. Phylogenetic aspects concerning the standing of the fragment of genetic apparatus controlling cell specialization, and the development of its inner hierarchy that involves subordination of some clusters to other ones.}, } @article {pmid11755116, year = {2001}, author = {Jancinová, V and Nosál, R and Drábiková, K and Danihelováa, E}, title = {Cooperation of chloroquine and blood platelets in inhibition of polymorphonuclear leukocyte chemiluminescence.}, journal = {Biochemical pharmacology}, volume = {62}, number = {12}, pages = {1629-1636}, doi = {10.1016/s0006-2952(01)00811-5}, pmid = {11755116}, issn = {0006-2952}, mesh = {Blood Platelets/*physiology ; Chloroquine/*pharmacology ; Humans ; Luminescent Measurements ; Neutrophils/*drug effects/metabolism ; Reactive Oxygen Species/analysis ; Serotonin/metabolism ; }, abstract = {Effect of activated blood platelets and chloroquine on concentration of reactive oxygen species produced by polymorphonuclear leukocytes (PMNL) stimulated with Ca(2+)-ionophore A23187 was investigated. Oxygen metabolites localized outside PMNL were visualized by isoluminol enhanced chemiluminescence, whereas chemiluminescence, enhanced with luminol and measured in the presence of the extracellular scavengers superoxide dismutase and catalase, was used for the detection of radicals originated intracellularly. Significant reduction of chemiluminescence was observed in the presence of platelets (added to PMNL in the physiological cell ratio 50:1) and of chloroquine (10 and 100 micromol/L). Although chloroquine decreased effectively both the extra- as well as the intracellular part of the chemiluminescence signal, the activity of platelets occurred largely outside PMNL. Serotonin liberated from platelets by A23187 appeared to be involved in inhibition of chemiluminescence; its concentrations achieved in platelet supernatants were found to be sufficient for elimination of PMNL-derived oxygen metabolites. The presented results indicated that chloroquine and blood platelets cooperate in inhibition of chemiluminescence because their common effect was found to be much more extensive than reduction induced by these inhibitors separately. Therefore, for accurate prediction of drug effect in the whole organism, the use of multicellular test systems seems to be pertinent.}, } @article {pmid11746218, year = {2001}, author = {Miyata, T and Suga, H}, title = {Divergence pattern of animal gene families and relationship with the Cambrian explosion.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {23}, number = {11}, pages = {1018-1027}, doi = {10.1002/bies.1147}, pmid = {11746218}, issn = {0265-9247}, mesh = {Animals ; Cell Communication/genetics ; Classification ; *Evolution, Molecular ; Genes ; Growth Substances/classification/*genetics ; Humans ; Protein Kinases/classification/*genetics ; Time Factors ; Vertebrates/genetics ; }, abstract = {There are many gene families that are specific to multicellular animals. These have either diverged from ancestral genes that are shared with fungi and/or plants or evolved from an ancestral gene unique to animals. The evolution of gene families involved in cell-cell communication and developmental control has been studied to establish whether the number of member genes increased dramatically immediately prior to or in concert with the Cambrian explosion. A molecular phylogeny-based analysis of several animal-specific gene families has revealed that gene diversification by duplication occurred during two active periods interrupted by a long intervening quiescent period. Intriguingly, the Cambrian explosion is situated in the silent period, indicating that there is no direct link between the first burst of gene diversification and the Cambrian explosion itself. The importance of gene recruitment as a possible molecular mechanism for morphological diversity, and its possible role for the Cambrian explosion, are discussed.}, } @article {pmid11732191, year = {2001}, author = {Ehlers, K and Kollmann, R}, title = {Primary and secondary plasmodesmata: structure, origin, and functioning.}, journal = {Protoplasma}, volume = {216}, number = {1-2}, pages = {1-30}, pmid = {11732191}, issn = {0033-183X}, mesh = {Cell Communication/*physiology ; Cell Wall/chemistry/metabolism/ultrastructure ; Intercellular Junctions/chemistry/*physiology/*ultrastructure ; Microscopy, Electron ; Models, Biological ; Plant Development ; Plant Leaves/growth & development/metabolism ; Plant Physiological Phenomena ; Plants/genetics/*ultrastructure ; }, abstract = {In the multicellular organisms of higher plants, plasmodesmata provide pathways for intimate symplasmic communication between neighboring cells. The arguments summarized in the present review demonstrate that plasmodesmata are diverse and highly dynamic structures. Differences in the plasmodesmal origin and modifications of the plasmodesmal structure and functioning at the various cell interfaces are the basic means which give rise to a complicated and flexibile symplasmic network. This complex communication system is discussed to serve a significant role in the coordinated development and in the concerted physiological functioning of the cells within the plant tissues, organs, and organisms.}, } @article {pmid11728310, year = {2001}, author = {de Freitas Balanco, JM and Moreira, ME and Bonomo, A and Bozza, PT and Amarante-Mendes, G and Pirmez, C and Barcinski, MA}, title = {Apoptotic mimicry by an obligate intracellular parasite downregulates macrophage microbicidal activity.}, journal = {Current biology : CB}, volume = {11}, number = {23}, pages = {1870-1873}, doi = {10.1016/s0960-9822(01)00563-2}, pmid = {11728310}, issn = {0960-9822}, mesh = {Animals ; *Apoptosis ; Down-Regulation/*physiology ; Hydra/*physiology ; Leishmania/*physiology ; Macrophages/*immunology/*microbiology ; }, abstract = {Programmed cell death by apoptosis of unnecessary or potentially harmful cells is clearly beneficial to multicellular organisms. Proper functioning of such a program demands that the removal of dying cells proceed without an inflammatory reaction. Phosphatidylserine (PS) is one of the ligands displayed by apoptotic cells that participates in their noninflammatory removal when recognized by neighboring phagocytes. PS ligation induces the release of transforming growth factor-beta (TGF-beta), an antiinflammatory cytokine that mediates the suppression of macrophage-mediated inflammation. In Hydra vulgaris, an organism that stands at the base of metazoan evolution, the selective advantage provided by apoptosis lies in the fact that Hydra can survive recycling apoptotic cells by phagocytosis. In unicellular organisms, it has been proposed that altruistic death benefits clonal populations of yeasts and trypanosomatids. Now we show that advantageous features of the apoptotic process can operate without death as the necessary outcome. Leishmania spp are able to evade the killing activity of phagocytes and establish themselves as obligate intracellular parasites. Amastigotes, responsible for disease propagation, similar to apoptotic cells, inhibit macrophage activity by exposing PS. Exposed PS participates in amastigote internalization. Recognition of this moiety by macrophages induces TGF-beta secretion and IL-10 synthesis, inhibits NO production, and increases susceptibility to intracellular leishmanial growth.}, } @article {pmid11726553, year = {2001}, author = {Kondrashov, FA and Koonin, EV}, title = {Origin of alternative splicing by tandem exon duplication.}, journal = {Human molecular genetics}, volume = {10}, number = {23}, pages = {2661-2669}, doi = {10.1093/hmg/10.23.2661}, pmid = {11726553}, issn = {0964-6906}, mesh = {Alternative Splicing/*genetics ; Amino Acid Sequence ; Animals ; Databases, Protein ; Evolution, Molecular ; Exons/*genetics ; *Gene Duplication ; Genetic Variation ; Humans ; Molecular Sequence Data ; Sequence Alignment ; Sequence Homology, Amino Acid ; Tandem Repeat Sequences/genetics ; }, abstract = {Genes with new functions often evolve by gene duplication. Alternative splicing is another means of evolutionary innovation in eukaryotes, which allows a single gene to encode functionally diverse proteins. We investigate a connection between these two evolutionary phenomena. For approximately 10% of the described cases of substitution alternative splicing, such that either one or another amino acid sequence is included into the protein, evidence of origin by tandem exon duplication was found. This is a conservative estimate because alternative exons are typically short and, on many occasions, duplicates may have diverged beyond recognition. Dating exon duplications through a combination of the available experimental data on alternative splicing in orthologous genes from different species and computational analysis indicates that most of the duplications antedate at least the radiation of mammalian orders or even the radiation of vertebrate classes. At present, tandem exon duplication is the only mechanism of evolution of substitution alternative splicing that can be specifically demonstrated. Along with gene duplication, this could be a major route for generating functional diversity during evolution of multicellular eukaryotes.}, } @article {pmid11712551, year = {1999}, author = {Marco, R and Diaz, C and Benguria, A and Mateos, J and Mas, J and de Juan, E}, title = {The role of gravity in the evolutionary emergence of multicellular complexity: microgravity effects on arthropod development and aging.}, journal = {Advances in space research : the official journal of the Committee on Space Research (COSPAR)}, volume = {23}, number = {12}, pages = {2075-2082}, doi = {10.1016/s0273-1177(99)00165-9}, pmid = {11712551}, issn = {0273-1177}, mesh = {Animals ; Artemia ; *Biological Evolution ; *Developmental Biology ; Drosophila melanogaster ; Embryo, Nonmammalian ; *Gravitation ; Gravity Sensing/*physiology ; Models, Animal ; *Weightlessness ; }, abstract = {While experiments carried out in Space with isolated cells have shown that eucaryotic cells are able to sense and respond to the absence of gravity by modifying their reactions, experiments in which more complex processes have been investigated, such as Biological Systems undergoing development under Microgravity, have been surprisingly unaffected by the space environment. This can be considered a curious result since all organisms are evolutionarily adapted to the current level of the gravity force in our planet and should eventually change if this parameter will vary in a permanent manner. In fact, the small effects of the modifications in gravity on development in short term experiments may be equivalent to the difficulties in detecting the involvement of other basic physical processes such as diffusion-controled auto-organizative reactions in currently developing biological systems. An apparent exception to this lack of effect is experiments where brine shrimp dormant gastrulae directly exposed to the space environment accumulate developmental defects as a consequence of cosmic irradiation. In this article we discuss the idea that at a certain stage during the evolutionary emergence of multicellular organisms the cues laid by generic forces such as gravity were involved in the evolutionary organization of these primitive organisms. As evolution proceed, these early mechanisms may have been obscured and/or made redundant by the appearance of new internal, environment-independent biological regulatory mechanisms. On the other hand, behavioral responses that may be important, for example, in setting the life-spans of organisms may still be more readily susceptible to manipulation by external cues as experiments carried out by our group in Space and on the ground with Drosophila melanogaster indicate. Grant Numbers: ESP-1775.}, } @article {pmid11710986, year = {2001}, author = {Giebultowicz, JM}, title = {Peripheral clocks and their role in circadian timing: insights from insects.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {356}, number = {1415}, pages = {1791-1799}, pmid = {11710986}, issn = {0962-8436}, mesh = {Animals ; Biological Evolution ; *Circadian Rhythm ; Drosophila/anatomy & histology/physiology ; Gene Expression Regulation ; Insecta/*anatomy & histology/*physiology ; Photoreceptor Cells, Invertebrate/physiology ; }, abstract = {Impressive advances have been made recently in our understanding of the molecular basis of the cell-autonomous circadian feedback loop; however, much less is known about the overall organization of the circadian systems. How many clocks tick in a multicellular animal, such as an insect, and what are their roles and the relationships between them? Most attempts to locate clock-containing tissues were based on the analysis of behavioural rhythms and identified brain-located timing centres in a variety of animals. Characterization of several essential clock genes and analysis of their expression patterns revealed that molecular components of the clock are active not only in the brain, but also in many peripheral organs of Drosophila and other insects as well as in vertebrates. Subsequent experiments have shown that isolated peripheral organs can maintain self-sustained and light sensitive cycling of clock genes in vitro. This, together with earlier demonstrations that physiological output rhythms persist in isolated organs and tissues, provide strong evidence for the existence of functionally autonomous local circadian clocks in insects and other animals. Circadian systems in complex animals may include many peripheral clocks with tissue-specific functions and a varying degree of autonomy, which seems to be correlated with their sensitivity to external entraining signals.}, } @article {pmid11709087, year = {2001}, author = {Beutler, B}, title = {Sepsis begins at the interface of pathogen and host.}, journal = {Biochemical Society transactions}, volume = {29}, number = {Pt 6}, pages = {853-859}, doi = {10.1042/0300-5127:0290853}, pmid = {11709087}, issn = {0300-5127}, mesh = {Animals ; Drosophila ; *Drosophila Proteins ; Endotoxins/pharmacology ; Humans ; Membrane Glycoproteins/chemistry/genetics/*physiology ; Mice ; Receptors, Cell Surface/chemistry/genetics/*physiology ; Sepsis/*microbiology/*physiopathology ; Toll-Like Receptor 5 ; Toll-Like Receptors ; }, abstract = {To the modern mind, the term 'sepsis' conjures up images of microbes. It is easy to forget that the word predates any understanding of the microbial origins of infectious disease. Derived from the Greek 'sepsios' (rotten), sepsis denotes decay: a phenomenon that humans once regarded as a mysterious though inevitable natural process. A living organism does not accept decay passively. Virtually all multicellular life forms are capable of resisting infection through the generation of a vigorous immune response. In mammals, the response is so stereotypic that it has come to define sepsis itself: it is often called the 'septic syndrome'. Our current understanding of the innate immune system is deeply rooted in the study of sepsis. The chain of events linking infection to tissue injury and cardiovascular collapse is not obvious, and affirmation of the concept required three major discoveries. First, the septic syndrome was found to be caused by toxic products of microbes. Secondly, these toxic substances were found to be toxic because of their propensity to activate cells of the innate immune system, prompting cytokine production. Thirdly, the activating events initiated by microbial toxins were traced to members of an ancient family of defensive molecules, versions of which operate in virtually all multicellular life forms. In mammals, proteins of this family are now known as Toll-like receptors. They represent a point of direct contact, and first contact, between a pathogen and the host immune system.}, } @article {pmid11707569, year = {2001}, author = {Kairies, N and Beisel, HG and Fuentes-Prior, P and Tsuda, R and Muta, T and Iwanaga, S and Bode, W and Huber, R and Kawabata, S}, title = {The 2.0-A crystal structure of tachylectin 5A provides evidence for the common origin of the innate immunity and the blood coagulation systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {98}, number = {24}, pages = {13519-13524}, pmid = {11707569}, issn = {0027-8424}, mesh = {Amino Acid Sequence ; Animals ; *Blood Coagulation ; Blood Proteins/*chemistry/immunology/physiology ; Crystallography, X-Ray ; *Evolution, Molecular ; Fibrinogen/chemistry ; Horseshoe Crabs ; Humans ; Immunity, Innate ; Lectins/*chemistry/immunology/physiology ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Folding ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid ; }, abstract = {Because invertebrates lack an adaptive immune system, they had to evolve effective intrinsic defense strategies against a variety of microbial pathogens. This ancient form of host defense, the innate immunity, is present in all multicellular organisms including humans. The innate immune system of the Japanese horseshoe crab Tachypleus tridentatus, serving as a model organism, includes a hemolymph coagulation system, which participates both in defense against microbes and in hemostasis. Early work on the evolution of vertebrate fibrinogen suggested a common origin of the arthropod hemolymph coagulation and the vertebrate blood coagulation systems. However, this conjecture could not be verified by comparing the structures of coagulogen, the clotting protein of the horseshoe crab, and of mammalian fibrinogen. Here we report the crystal structure of tachylectin 5A (TL5A), a nonself-recognizing lectin from the hemolymph plasma of T. tridentatus. TL5A shares not only a common fold but also related functional sites with the gamma fragment of mammalian fibrinogen. Our observations provide the first structural evidence of a common ancestor for the innate immunity and the blood coagulation systems.}, } @article {pmid11700279, year = {2001}, author = {Kaiser, D}, title = {Building a multicellular organism.}, journal = {Annual review of genetics}, volume = {35}, number = {}, pages = {103-123}, doi = {10.1146/annurev.genet.35.102401.090145}, pmid = {11700279}, issn = {0066-4197}, support = {GM23441/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Cell Differentiation ; Cell Division ; Cell Membrane/physiology ; Cell Wall/physiology ; Chlorophyta/*physiology ; Cyanobacteria/*physiology ; Myxococcales/*physiology ; Photosynthesis ; Signal Transduction ; }, abstract = {Multicellular organisms appear to have arisen from unicells numerous times. Multicellular cyanobacteria arose early in the history of life on Earth. Multicellular forms have since arisen independently in each of the kingdoms and several times in some phyla. If the step from unicellular to multicellular life was taken early and frequently, the selective advantage of multicellularity may be large. By comparing the properties of a multicellular organism with those of its putative unicellular ancestor, it may be possible to identify the selective force(s). The independent instances of multicellularity reviewed indicate that advantages in feeding and in dispersion are common. The capacity for signaling between cells accompanies the evolution of multicellularity with cell differentiation.}, } @article {pmid11682006, year = {2001}, author = {Paunesku, T and Mittal, S and Protić, M and Oryhon, J and Korolev, SV and Joachimiak, A and Woloschak, GE}, title = {Proliferating cell nuclear antigen (PCNA): ringmaster of the genome.}, journal = {International journal of radiation biology}, volume = {77}, number = {10}, pages = {1007-1021}, doi = {10.1080/09553000110069335}, pmid = {11682006}, issn = {0955-3002}, support = {CA73042/CA/NCI NIH HHS/United States ; CA81375/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Cell Survival ; DNA Repair ; *Genome ; Humans ; Molecular Sequence Data ; Proliferating Cell Nuclear Antigen/chemistry/genetics/*physiology ; Radiation Tolerance ; }, abstract = {Proliferating cell nuclear antigen (PCNA) protein is one of the central molecules responsible for decisions of life and death of the cell. The PCNA gene is induced by p53, while PCNA protein interacts with p53-controlled proteins Gadd45, MyD118, CR6 and, most importantly, p21, in the process of deciding cell fate. If PCNA protein is present in abundance in the cell in the absence of p53, DNA replication occurs. On the other hand, if PCNA protein levels are high in the cell in the presence of p53, DNA repair takes place. If PCNA is rendered non-functional or is absent or present in low quantities in the cell, apoptosis occurs. The evolution from prokaryotes to eukaryotes involved a change of function of PCNA from a 'simple' sliding clamp protein of the DNA polymerase complex to an executive molecule controlling critical cellular decision pathways. The evolution of multicellular organisms led to the development of multicellular processes such as differentiation, senescence and apoptosis. PCNA, already an essential molecule in the life of single cellular organisms, then became a protein critical for the survival of multicellular organisms.}, } @article {pmid11675609, year = {2001}, author = {Rodríguez-Trelles, F and Tarrío, R and Ayala, FJ}, title = {Xanthine dehydrogenase (XDH): episodic evolution of a "neutral" protein.}, journal = {Journal of molecular evolution}, volume = {53}, number = {4-5}, pages = {485-495}, doi = {10.1007/s002390010239}, pmid = {11675609}, issn = {0022-2844}, support = {GM42397/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Substitution ; Amino Acids/analysis ; Animals ; Base Composition ; DNA/chemistry/genetics ; Diptera/enzymology/genetics ; Drosophila/enzymology/genetics ; *Evolution, Molecular ; Models, Genetic ; Phylogeny ; Xanthine Dehydrogenase/chemistry/*genetics ; }, abstract = {We investigated the evolution of xanthine dehydrogenase (Xdh) in 34 species from the three multicellular kingdoms, including one plant, two fungi, and three animal phyla, two classes of vertebrates, four orders of mammals, and two orders of insects. We adopted a model-based maximum-likelihood framework of inference. After accounting for among-site rate variation and heterogeneous nucleotide composition of the sequences using the discrete gamma distribution, and using nonhomogeneous nonstationary representations of the substitution process, the rate of amino acid replacement is 30.4 x 10(-10)/site/year when Drosophila species are compared but only approximately 18 x 10(-10)/site/year when comparisons are made between mammal orders, between insect orders, or between different animal phyla and approximately 11 x 10(-10)/site/year when comparisons are made between birds and mammals, between fungi, or between the three multicellular kingdoms. To account for these observations, the rate of amino acid replacement must have been eight or more times higher in some lineages and at some times than in others. Spastic evolution of Xdh appears to be related to the particularities of the genomes in which the locus is embedded.}, } @article {pmid11675607, year = {2001}, author = {Sueoka, N}, title = {Near homogeneity of PR2-bias fingerprints in the human genome and their implications in phylogenetic analyses.}, journal = {Journal of molecular evolution}, volume = {53}, number = {4-5}, pages = {469-476}, doi = {10.1007/s002390010237}, pmid = {11675607}, issn = {0022-2844}, mesh = {Base Composition ; Codon/genetics ; DNA/*chemistry/*genetics ; DNA Fingerprinting ; Evolution, Molecular ; *Genome, Human ; Humans ; *Phylogeny ; }, abstract = {Genes of a multicellular organism are heterogeneous in the G+C content, which is particularly true in the third codon position. The extent of deviation from intra-strand equality rule of A = T and G = C (Parity Rule 2, or PR2) is specific for individual amino acids and has been expressed as the PR2-bias fingerprint. Previous results suggested that the PR2-bias fingerprints tend to be similar among the genes of an organism, and the fingerprint of the organism is specific for different taxa, reflecting phylogenetic relationships of organisms. In this study, using coding sequences of a large number of human genes, we examined the intragenomic heterogeneity of their PR2-bias fingerprints in relation to the G+C content of the third codon position (P3). Result shows that the PR2-bias fingerprint is similar in the wide range of the G+C content at the third codon position (0.30-0.80). This range covers approximately 89% of the genes, and further analysis of the high G+C range (0.80-1.00), where genes with normal PR2-bias fingerprints and those with anomalous fingerprints are mixed, shows that the total of 95% of genes have the similar finger prints. The result indicates that the PR2-bias fingerprint is a unique property of an organism and represents the overall characteristics of the genome. Combined with the previous results that the evolutionary change of the PR2-bias fingerprint is a slow process, PR2-bias fingerprints may be used for the phylogenetic analyses to supplement and augment the conventional methods that use the differences of the sequences of orthologous proteins and nucleic acids. Potential advantages and disadvantages of the PR2-bias fingerprint analysis are discussed.}, } @article {pmid11675600, year = {2001}, author = {Schütze, J and Skorokhod, A and Müller, IM and Müller, WE}, title = {Molecular evolution of the metazoan extracellular matrix: cloning and expression of structural proteins from the demosponges Suberites domuncula and Geodia cydonium.}, journal = {Journal of molecular evolution}, volume = {53}, number = {4-5}, pages = {402-415}, doi = {10.1007/s002390010230}, pmid = {11675600}, issn = {0022-2844}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Carrier Proteins/genetics/pharmacology ; Cell Adhesion Molecules/genetics/pharmacology ; Cell Aggregation/drug effects ; Chondroitin Sulfate Proteoglycans ; Cloning, Molecular ; Collagen/genetics ; DNA, Complementary/genetics ; Evolution, Molecular ; Extracellular Matrix Proteins/*genetics ; Gene Expression ; Growth Substances/pharmacology ; *Intercellular Signaling Peptides and Proteins ; Molecular Sequence Data ; Phylogeny ; Porifera/cytology/drug effects/*genetics ; Receptor Protein-Tyrosine Kinases/genetics ; Recombinant Proteins/pharmacology ; Sequence Homology, Amino Acid ; Transplantation, Autologous ; }, abstract = {One crucial event during evolution to multicellularity was the development of either direct cell-cell contact or indirect interaction via extracellular matrix (ECM) molecules. The identification of those polypeptides provides conclusive data on the phylogenetic relationship of metazoan phyla and helps us to understand the position of the Metazoa among the other kingdoms. Recently it became evident that the ECM of sponges is amazingly complex; it is composed of fibrous molecules, e.g., collagen, and their corresponding receptors, which are highly similar to those existing in other metazoan phyla. While these data already support the view of monophyly of Metazoa, additional studies are required to understand whether these molecules, which are similar in their primary sequence, also have the same function throughout the metazoan kingdom. In the present study we identified the ligand for one of the autopomorphic characters of Metazoa, the single-transmembrane receptor protein with the receptor tyrosine kinase (RTK) from G. cydonium, as an example: the putative mucus-like protein from G. cydonium. This protein was upregulated during autograft fusion in the homologous system with kinetics similar to those of the RTK. Additionally, a cDNA was isolated from S. domuncula whose deduced polypeptide displays a high sequence similarity to dermatopontin, an ECM molecule found exclusively in Metazoa. Furthermore, it is documented that expression of the fibrous ECM molecule collagen is regulated by the characteristic metazoan morphogens myotrophin and endothelial monocyte-activating polypeptide. These data indicate that the ECM of sponges is not an unstructured ground substance but provides the basis for integrated cell communication.}, } @article {pmid11602194, year = {2001}, author = {Zarkadis, IK and Mastellos, D and Lambris, JD}, title = {Phylogenetic aspects of the complement system.}, journal = {Developmental and comparative immunology}, volume = {25}, number = {8-9}, pages = {745-762}, doi = {10.1016/s0145-305x(01)00034-9}, pmid = {11602194}, issn = {0145-305X}, support = {AI 30040/AI/NIAID NIH HHS/United States ; AI 48487/AI/NIAID NIH HHS/United States ; GM 56698/GM/NIGMS NIH HHS/United States ; HL 28220/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Complement System Proteins/*genetics ; Fishes/*genetics/*immunology ; Gene Duplication ; Humans ; Immunity, Innate/genetics ; Invertebrates/genetics/immunology ; *Phylogeny ; }, abstract = {During evolution two general systems of immunity have emerged: innate or, natural immunity and adaptive (acquired), or specific immunity. The innate system is phylogenetically older and is found in some form in all multicellular organisms, whereas the adaptive system appeared about 450 million years ago and is found in all vertebrates except jawless fish. The complement system in higher vertebrates plays an important role as an effector of both the innate and the acquired immune response, and also participates in various immunoregulatory processes. In lower vertebrates complement is activated by the alternative and lectin pathways and is primarily involved in the opsonization of foreign material. The Agnatha (the most primitive vertebrate species) possess the alternative and lectin pathways while cartilaginous fish are the first species in which the classical pathway appears following the emergence of immunoglobulins. The rest of the poikilothermic species, ranging from teleosts to reptilians, appear to contain a well-developed complement system resembling that of the homeothermic vertebrates. It seems that most of the complement components have appeared after the duplication of primordial genes encoding C3/C4/C5, fB/C2, C1s/C1r/MASP-1/MASP-2, and C6/C7/C8/C9 molecules, in a process that led to the formation of distinct activation pathways. However, unlike homeotherms, several species of poikilotherms (e.g. trout) have recently been shown to possess multiple forms of complement components (C3, factor B) that are structurally and functionally more diverse than those of higher vertebrates. We hypothesize that this remarkable diversity has allowed these animals to expand their innate capacity for immune recognition and response. Recent studies have also indicated the possible presence of complement receptors in protochordates and lower vertebrates. In conclusion, there is considerable evidence suggesting that the complement system is present in the entire lineage of deuterostomes, and regulatory complement components have been identified in all species beyond the protochordates, indicating that the mechanisms of complement activation and regulation have developed in parallel.}, } @article {pmid11601608, year = {2001}, author = {Ehlers, RU}, title = {Mass production of entomopathogenic nematodes for plant protection.}, journal = {Applied microbiology and biotechnology}, volume = {56}, number = {5-6}, pages = {623-633}, doi = {10.1007/s002530100711}, pmid = {11601608}, issn = {0175-7598}, mesh = {Animals ; Bioreactors ; Biotechnology/*methods ; Insecta/*parasitology ; Nematoda/*growth & development/microbiology/pathogenicity ; *Pest Control, Biological ; Photorhabdus/growth & development ; Plants/*parasitology ; Symbiosis ; Xenorhabdus/growth & development ; }, abstract = {Entomopathogenic nematodes of the genera Heterorhabditis and Steinernema are commercially used to control pest insects. They are symbiotically associated with bacteria of the genera Photorhabdus and Xenorhabdus, respectively, which are the major food source for the nematodes. The biology of the nematode-bacterium complex is described, a historical review of the development of in vitro cultivation techniques is given and the current use in agriculture is summarised. Cultures of the complex are pre-incubated with the symbiotic bacteria before the nematodes are inoculated. Whereas the inoculum preparation and preservation of bacterial stocks follow standard rules, nematodes need special treatment. Media development is mainly directed towards cost reduction, as the bacteria are able to metabolise a variety of protein sources to provide optimal conditions for nematode reproduction. The process technology is described, discussing the influence of bioreactor design and process parameters required to obtain high nematode yields. As two organisms are grown in one vessel and one of them is a multicellular organism, the population dynamics and symbiotic interactions need to be understood in order to improve process management. Major problems can originate from the delayed or slow development of the nematode inoculum and from phase variants of the symbiotic bacteria that have negative effects on nematode development and reproduction. Recent scientific progress has helped to understand the biological and technical parameters that influence the process, thus enabling transfer to an industrial scale. As a consequence, costs for nematode-based products could be significantly reduced.}, } @article {pmid11600899, year = {2001}, author = {David, JR}, title = {Evolution and development: some insights from evolutionary theory.}, journal = {Anais da Academia Brasileira de Ciencias}, volume = {73}, number = {3}, pages = {385-395}, doi = {10.1590/s0001-37652001000300008}, pmid = {11600899}, issn = {0001-3765}, mesh = {Animals ; *Biological Evolution ; *Developmental Biology ; Eye/embryology ; Genetics ; Humans ; Morphogenesis ; Reproduction ; }, abstract = {Developmental biology and evolutionary biology are both mature integrative disciplines which started in the 19th century and then followed parallel and independent scientific pathways. Recently, a genetical component has stepped into both disciplines (developmental genetics and evolutionary genetics) pointing out the need for future convergent maturation. Indeed, the Evo-Devo approach is becoming popular among developmental biologists, based on the facts that distant groups share a common ancestry, that precise phylogenies can be worked out and that homologous genes often play similar roles during the development of very different organisms. In this essay, I try to show that the real future of Evo-Devo thinking is still broader. The evolutionary theory is a set of diverse concepts which can and should be used in any biological field. Evolutionary thinking trains to ask << why >> questions and to provide logical and plausible answers. It can shed some light on a diversity of general problems such as how to distinguish homologies from analogies, the costs and benefits of multicellularity, the origin of novel structures (e.g. the head), or the evolution of sexual reproduction. In the next decade, we may expect a progressive convergence between developmental genetics and quantitative genetics.}, } @article {pmid11598188, year = {2001}, author = {Arnoult, D and Tatischeff, I and Estaquier, J and Girard, M and Sureau, F and Tissier, JP and Grodet, A and Dellinger, M and Traincard, F and Kahn, A and Ameisen, JC and Petit, PX}, title = {On the evolutionary conservation of the cell death pathway: mitochondrial release of an apoptosis-inducing factor during Dictyostelium discoideum cell death.}, journal = {Molecular biology of the cell}, volume = {12}, number = {10}, pages = {3016-3030}, pmid = {11598188}, issn = {1059-1524}, mesh = {Amino Acid Sequence ; Animals ; Apoptosis/*physiology ; Apoptosis Inducing Factor ; Cell Nucleus/metabolism ; Cell-Free System ; Cytosol/metabolism ; DNA Fragmentation/physiology ; Dictyostelium/*physiology/ultrastructure ; *Evolution, Molecular ; Flavoproteins/chemistry/*genetics/*metabolism ; Humans ; Jurkat Cells ; Mammals/physiology ; Membrane Potentials/physiology ; Membrane Proteins/chemistry/*genetics/*metabolism ; Mitochondria/metabolism ; Molecular Sequence Data ; Phagocytosis/physiology ; Phosphatidylserines/metabolism ; Protoporphyrins/chemistry/*metabolism ; Sequence Homology ; }, abstract = {Mitochondria play a pivotal role in apoptosis in multicellular organisms by releasing apoptogenic factors such as cytochrome c that activate the caspases effector pathway, and apoptosis-inducing factor (AIF) that is involved in a caspase-independent cell death pathway. Here we report that cell death in the single-celled organism Dictyostelium discoideum involves early disruption of mitochondrial transmembrane potential (DeltaPsim) that precedes the induction of several apoptosis-like features, including exposure of the phosphatidyl residues at the external surface of the plasma membrane, an intense vacuolization, a fragmentation of DNA into large fragments, an autophagy, and the release of apoptotic corpses that are engulfed by neighboring cells. We have cloned a Dictyostelium homolog of mammalian AIF that is localized into mitochondria and is translocated from the mitochondria to the cytoplasm and the nucleus after the onset of cell death. Cytoplasmic extracts from dying Dictyostelium cells trigger the breakdown of isolated mammalian and Dictyostelium nuclei in a cell-free system, and this process is inhibited by a polyclonal antibody specific for Dictyostelium discoideum apoptosis-inducing factor (DdAIF), suggesting that DdAIF is involved in DNA degradation during Dictyostelium cell death. Our findings indicate that the cell death pathway in Dictyostelium involves mitochondria and an AIF homolog, suggesting the evolutionary conservation of at least part of the cell death pathway in unicellular and multicellular organisms.}, } @article {pmid11596926, year = {2001}, author = {Lasek-Nesselquist, E and Katz, LA}, title = {Phylogenetic position of Sorogena stoianovitchae and relationships within the class Colpodea (Ciliophora) based on SSU rDNA sequences.}, journal = {The Journal of eukaryotic microbiology}, volume = {48}, number = {5}, pages = {604-607}, doi = {10.1111/j.1550-7408.2001.tb00197.x}, pmid = {11596926}, issn = {1066-5234}, mesh = {Animals ; Ciliophora/*classification/*genetics ; DNA, Protozoan/analysis ; DNA, Ribosomal/*analysis ; Molecular Sequence Data ; *Phylogeny ; RNA, Ribosomal/*genetics ; *Sequence Analysis, DNA ; }, abstract = {The ciliate Sorogena stoianovitchae, which can form a multicellular fruiting body, has been classified based upon its ultrastructure and morphology: the oral and somatic infraciliature of S. stoianovitchae most closely resemble those of members of the order Cyrtolophosidida in the class Colpodea. We characterized the small subunit ribosomal DNA (SSU rDNA) gene sequence from S. stoianovitchae and compared this sequence with those from representatives of all ciliate classes. These analyses placed S. stoianovitchae as either sister to members of the class Nassophorea or Colpodea. In an in-group analysis, including all SSU rDNA sequences from members of the classes Nassophorea and Colpodea and representatives of appropriate outgroups, S. stoianovitchae was always sister to Platyophrya vorax (class Colpodea, order Cyrtolophosidida). However, our analyses failed to support the monophyly of the class Colpodea. Instead, our data suggest that there are essentially three unresolved clades: (1) the class Nassophorea; (2) Bresslaua vorax, Colpoda inflata, Pseudoplatyophrya nana, and Bursaria truncatella (class Colpodea); and (3) P. vorax and S. stoianovitchae (class Colpodea).}, } @article {pmid11596880, year = {2001}, author = {Koch, AL}, title = {Can synchronous cultures of bacteria be manufactured?.}, journal = {Critical reviews in microbiology}, volume = {27}, number = {3}, pages = {223-237}, doi = {10.1080/20014091096756}, pmid = {11596880}, issn = {1040-841X}, mesh = {Bacteria/*growth & development ; Cell Cycle ; Cell Division ; Culture Media ; *Monte Carlo Method ; }, abstract = {The bacterial cell cycle is simpler and different than that of the typical eukaryotic cell cycle. The selective pressure during evolution has been directed to achieve optimal growth of the individual free-living microbial cell instead of a variety of replication rates of the differentiated cell within an entire multicellular organism. This means that for most bacterial cells division depends more critically on their success in acquiring and using resources than is the case for most eukaryotic cells. The further implication is that bacterial cells somehow measure their own success in growth and from this 'decide' when they should attempt cell cycle events such as cell division and chromosome replication. On the assumption that bacterial division is responsive, directly or indirectly, to cell size, the cell cycle is analyzed here through Monte Carlo simulations. The results are used to consider the possibility of generating bacterial cultures growing synchronous. Because the precision of the size-at-division is surprisingly good, it appears that some organisms, at least, have a sensory mechanism that responds to their success in cell growth. It is known that the division size of some strains, however, is more precisely regulated than in others. Also, some strains are more precise in dividing the mother's cell cytoplasm to give the same sized daughters. Because some strains are much more precise than others, the possibility is raised that useful synchrony could be obtained with selected strains that are precise in these two aspects. These cultures would useful in studying other aspect of the physiology of cell growth.}, } @article {pmid11595174, year = {2001}, author = {Li, QZ and Wang, CY and Shi, JD and Ruan, QG and Eckenrode, S and Davoodi-Semiromi, A and Kukar, T and Gu, Y and Lian, W and Wu, D and She, JX}, title = {Molecular cloning and characterization of the mouse and human TUSP gene, a novel member of the tubby superfamily.}, journal = {Gene}, volume = {273}, number = {2}, pages = {275-284}, doi = {10.1016/s0378-1119(01)00582-0}, pmid = {11595174}, issn = {0378-1119}, support = {P01 AI-42288/AI/NIAID NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing ; Alternative Splicing ; Amino Acid Sequence ; Animals ; Blotting, Northern ; Cell Line ; Chromosome Mapping ; Chromosomes, Human, Pair 6/genetics ; Cloning, Molecular ; Cytoplasm/metabolism ; DNA, Complementary/chemistry/genetics ; Diabetes Mellitus/genetics ; Dinucleotide Repeats/genetics ; Female ; Gene Expression ; Genes/genetics ; Green Fluorescent Proteins ; Humans ; Intracellular Signaling Peptides and Proteins ; Luminescent Proteins/genetics/metabolism ; Male ; Mice ; Molecular Sequence Data ; Phylogeny ; Polymorphism, Genetic ; Proteins/*genetics ; RNA, Messenger/genetics/metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Tissue Distribution ; }, abstract = {We report here the cloning and characterization of a novel gene belonging to the tubby superfamily proteins (TUSP) in mouse and human. The mouse Tusp cDNA is 9120 bp in length and encodes a deduced protein of 1547 amino acids, while the human TUSP gene is 11,127 bp and encodes a deduced protein of 1544 amino acids. The human and mouse genes are 87% identical for their nucleotide sequences and 85% identical for their amino acid sequences. The protein sequences of these genes are 40-48% identical to other tubby family proteins at the C-terminal conserved 'tubby domain'. In addition, the TUSP proteins contain a tubby signature motif (FXGRVTQ), two bipartite nuclear localization signals (NLSs) at the C-terminal, two proline-rich regions, one WD40 repeat region and one suppressor of cytokines signaling domain. Transfection assay with green fluorescent protein-tagged TUSP expression constructs showed that the complete TUSP protein and the N-terminal portion of TUSP are localized in the cytoplasm but the C-terminal portion with the two NLSs produced distinct dots or spots localized in the cytoplasm. Northern blotting analysis showed that the major transcript with the complete coding sequence is expressed mainly in the brain, skeletal muscle, testis and kidney. Radiation hybrid mapping localized the mouse gene to chromosome 17q13 and the human TUSP gene to chromosome 6q25-q26 near the type 1 diabetes gene IDDM5. However, association analysis in diabetic families with a polymorphic microsatellite marker did not show any evidence for association between TUSP and type 1 diabetes. The precise biological function of the tubby superfamily genes is still unknown; the highly conserved tubby domain in different species, however, suggests that these proteins must have fundamental biological functions in a wide range of multi-cellular organisms.}, } @article {pmid11588247, year = {2001}, author = {Avise, JC}, title = {Evolving genomic metaphors: a new look at the language of DNA.}, journal = {Science (New York, N.Y.)}, volume = {294}, number = {5540}, pages = {86-87}, doi = {10.1126/science.294.5540.86}, pmid = {11588247}, issn = {0036-8075}, mesh = {Animals ; DNA Transposable Elements ; *DNA, Intergenic ; Evolution, Molecular ; Exons ; Gene Expression Regulation ; *Genome ; *Genome, Human ; Humans ; Introns ; *Metaphor ; Repetitive Sequences, Nucleic Acid ; Research ; }, abstract = {Recent genome-sequencing efforts have confirmed that traditional "good-citizen" genes (those that encode functional RNA and protein molecules of obvious benefit to the organism) constitute only a small fraction of the genomic populace in humans and other multicellular creatures. The rest of the DNA sequence includes an astonishing collection of noncoding regions, regulatory modules, deadbeat pseudogenes, legions of repetitive elements, and hosts of oft-shifty, self-interested nomads, renegades, and immigrants. To help visualize functional operations in such intracellular genomic societies and to better encapsulate the evolutionary origins of complex genomes, new and evocative metaphors may be both entertaining and research-stimulating.}, } @article {pmid11571074, year = {2001}, author = {Devauchelle, C and Grossmann, A and Hénaut, A and Holschneider, M and Monnerot, M and Risler, JL and Torrésani, B}, title = {Rate matrices for analyzing large families of protein sequences.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {8}, number = {4}, pages = {381-399}, doi = {10.1089/106652701752236205}, pmid = {11571074}, issn = {1066-5277}, mesh = {*Computational Biology ; Computer Simulation ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Markov Chains ; Phylogeny ; Proteins/*genetics ; Sequence Alignment/*statistics & numerical data ; Sequence Analysis, Protein/statistics & numerical data ; Stochastic Processes ; }, abstract = {We propose and study a new approach for the analysis of families of protein sequences. This method is related to the LogDet distances used in phylogenetic reconstructions; it can be viewed as an attempt to embed these distances into a multidimensional framework. The proposed method starts by associating a Markov matrix to each pairwise alignment deduced from a given multiple alignment. The central objects under consideration here are matrix-valued logarithms L of these Markov matrices, which exist under conditions that are compatible with fairly large divergence between the sequences. These logarithms allow us to compare data from a family of aligned proteins with simple models (in particular, continuous reversible Markov models) and to test the adequacy of such models. If one neglects fluctuations arising from the finite length of sequences, any continuous reversible Markov model with a single rate matrix Q over an arbitrary tree predicts that all the observed matrices L are multiples of Q. Our method exploits this fact, without relying on any tree estimation. We test this prediction on a family of proteins encoded by the mitochondrial genome of 26 multicellular animals, which include vertebrates, arthropods, echinoderms, molluscs, and nematodes. A principal component analysis of the observed matrices L shows that a single rate model can be used as a rough approximation to the data, but that systematic deviations from any such model are unmistakable and related to the evolutionary history of the species under consideration.}, } @article {pmid11569142, year = {2001}, author = {Zmitrovich, IV}, title = {[On the problem og higher fungi origin: Florideae hypothesis].}, journal = {Zhurnal obshchei biologii}, volume = {62}, number = {4}, pages = {296-314}, pmid = {11569142}, issn = {0044-4596}, mesh = {Ascomycota ; Basidiomycota ; *Biological Evolution ; Fungi/*classification ; Phylogeny ; Rhodophyta ; }, abstract = {The history and current state of the hypothesis of the origin of higher fungi (Ascomycetes and Basidiomycetes) and red algae from the common ancestor (Florideae) were analysed. Initially the hypothesis was based on similarity of their vegetative and generative structures (Sachs, 1874; Dodge, 1914; Chadefaund, 1953, 1972, etc.), but later it was confirmed by ultrastructural data (Demoulin, 1974; Kohlmeyer, 1975). It appears to be very useful for the study of the development of terrestrial flora (Church, 1921; Kohlemeyer, Kohlmeyer, 1979; Atsatt, 1988) and regularities in morphological evolution of higher fungi (Corner, 1964, 1970; Chadefaud, 1960, 1982, 1984). Description of the order Spathulosporales (Kohlmeyer, 1973), combining the characters of Ascomycetes and parasitic Florideae, was one of the most important fact leading to the wide recognition of the hypothesis in 1970-80s (Cavalier-Smith, 1978; Taylor, 1978; Dodge, 1980; Hawksworth, 1982; Goff, 1983; Coff, Coleman, 1985). Today, however, Florideae hypothesis is not confirmed by molecular data and replaced by alternative hypothesis of Eumycota origin. Summarizing data on molecular systematic of fungi, one could affirm with confidence: 1). Chitincontaining fungi are closer to multicellular animals and green plants than to Rhodophyta; 2). Rhodophyta and Chlorophyta are monophyletic group; 3). There is no single-valued molecular data on taxonomic distance between higher fungi, Chytridiomycetes; Rhodophyta, Chlorophyta and Metazoa. Thus, the current data could not testify against Florideae hypothesis. It is possible to adjust them with the idea of B.M. Kozo-Polyansky (1927) about existence of "Chloroflorodeae" group that is original for terrestrial flora; the hypothesis about closeness of Chlorophyta and Rhodophyta, as well as Chlorophyta and Eumycota, does not contradict molecular data (Stiller, Hall, 1997). The author believes that we need molecular study of the whole "stem" of chlorobionta, especially groups that are close to its basis. It will will help to understand the relationships between Rhodophyta, giant conglomeration of "green algae", chitin-containing fungi, Prasinophyceae and different groups of zoomastigot with maximal resolution--the level of orders or groups of orders. Only such investigation could provide the material for molecular support of phylogenetic constructions. Up to moment Florideae hypothesis is able to exist together with the other ideas.}, } @article {pmid11566101, year = {2001}, author = {Bielinsky, AK and Blitzblau, H and Beall, EL and Ezrokhi, M and Smith, HS and Botchan, MR and Gerbi, SA}, title = {Origin recognition complex binding to a metazoan replication origin.}, journal = {Current biology : CB}, volume = {11}, number = {18}, pages = {1427-1431}, doi = {10.1016/s0960-9822(01)00444-4}, pmid = {11566101}, issn = {0960-9822}, support = {CA 30490/CA/NCI NIH HHS/United States ; GM 35929/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/genetics/*metabolism ; Adenosine Triphosphate/*analogs & derivatives/metabolism/pharmacology ; Animals ; Base Sequence ; Binding Sites ; *DNA Replication ; DNA, Complementary ; DNA-Binding Proteins/genetics/*metabolism ; Diptera/genetics/metabolism ; Insect Proteins/genetics/*metabolism ; Molecular Sequence Data ; Origin Recognition Complex ; *Replication Origin ; }, abstract = {The initiation of DNA replication in eukaryotic cells at the onset of S phase requires the origin recognition complex (ORC) [1]. This six-subunit complex, first isolated in Saccharomyces cerevisiae [2], is evolutionarily conserved [1]. ORC participates in the formation of the prereplicative complex [3], which is necessary to establish replication competence. The ORC-DNA interaction is well established for autonomously replicating sequence (ARS) elements in yeast in which the ARS consensus sequence [4] (ACS) constitutes part of the ORC binding site [2, 5]. Little is known about the ORC-DNA interaction in metazoa. For the Drosophila chorion locus, it has been suggested that ORC binding is dispersed [6]. We have analyzed the amplification origin (ori) II/9A of the fly, Sciara coprophila. We identified a distinct 80-base pair (bp) ORC binding site and mapped the replication start site located adjacent to it. The binding of ORC to this 80-bp core region is ATP dependent and is necessary to establish further interaction with an additional 65-bp of DNA. This is the first time that both the ORC binding site and the replication start site have been identified in a metazoan amplification origin. Thus, our findings extend the paradigm from yeast ARS1 to multicellular eukaryotes, implicating ORC as a determinant of the position of replication initiation.}, } @article {pmid11560369, year = {2001}, author = {Heininger, K}, title = {The deprivation syndrome is the driving force of phylogeny, ontogeny and oncogeny.}, journal = {Reviews in the neurosciences}, volume = {12}, number = {3}, pages = {217-287}, doi = {10.1515/revneuro.2001.12.3.217}, pmid = {11560369}, issn = {0334-1763}, mesh = {Aging/physiology ; Animals ; Apoptosis/physiology ; Cell Communication/physiology ; Cell Differentiation/physiology ; Energy Metabolism/*physiology ; General Adaptation Syndrome/*physiopathology ; Homeostasis ; Mitochondria/metabolism ; Mutagenesis ; Neoplasms/*physiopathology ; *Phylogeny ; Prokaryotic Cells/*physiology ; Sex ; Signal Transduction/physiology ; *Stress, Physiological ; }, abstract = {Energy is the motor of life. Energy ensures the organism's survival and competitive advantage for reproductive success. For almost 3 billion years, unicellular organisms were the only life form on earth. Competition for limited energy resources and raw materials exerted an incessant selective pressure on organisms. In the adverse environment and due to their 'feast and famine' life style, hardiness to a variety of stressors, particularly to nutrient deprivation, was the selection principle. Both resistance and mutagenic adaptation to stressors were established as survival strategies by means of context-specific processes creating stability or variability of DNA sequence. The conservation of transduction pathways and functional homology of effector molecules clearly bear witness that the principles of life established during prokaryotic and eukaryotic unicellular evolution, although later diversified, have been unshakably cast to persist during metazoan phylogenesis. A wealth of evidence suggests that unicellular organisms evolved the phenomena of differentiation and apoptosis, sexual reproduction, and even aging, as responses to environmental challenges. These evolutionary accomplishments were elaborated from the dichotomous resistance/mutagenesis response and sophisticated the capacity of cells to tune their genetic information to changing environmental conditions. Notably, the social deprivation responses, differentiation and apoptosis, evolved as intercellularly coordinated events: a multitude of differentiation processes were elaborated from sporulation, the prototypic stress resistance response, while apoptosis, contrary to current concepts, is no altruistic cell suicide but was programmed as a mutagenic survival response; this response, however, is socially thwarted leading into mutagenic error catastrophe. In the hybrid differentiation-apoptosis process, cytocide and cannibalism of apoptotic cells thus serve the purpose of fueling the survival of the selfish genes in the differentiating cells. However, successful mutagenesis, although repressed, persisted in the asocial stress response of carcinogenesis as a regression to primitive unicellular behavior following failure of intercellular communication. While somatic mutagenesis was largely prevented, Metazoa elaborated germ cell mutagenesis as an evolutionary vehicle. Genetic competence, a primitive, stress-induced mating behavior, evolved into sexual reproduction which harnessed mutagenesis by subjecting highly mutable germ cells to a rigid viability selection. These processes were programmatically fixed as life- and cell-cycle events but retained their deprivation response phenotypes. Thus, the differentiation-apoptosis tandem evolved as the 'clay' to mold the specialized structures and functions of a multicellular organism while sexual reproduction elaborated the principle of quality-checked mutagenesis to create the immense diversity of Metazoa following the Cambrian explosion. Throughout these events, reactive oxygen and nitrogen species, which are regulated by energy homeostasis, shape the genetic information in a regulated but random, uncoded process providing the fitness-related feedback of phenotype to genotype. The interplay of genes and environment establishes a dynamic stimulus-response feedback cycle which, in animate nature, may be the organizing principle to contrive the reciprocal duality of energy and matter.}, } @article {pmid11553344, year = {2001}, author = {Dolan, L}, title = {Plant development: the benefits of a change of scene.}, journal = {Current biology : CB}, volume = {11}, number = {17}, pages = {R702-4}, doi = {10.1016/s0960-9822(01)00413-4}, pmid = {11553344}, issn = {0960-9822}, mesh = {Animals ; Arabidopsis/genetics/growth & development ; *Arabidopsis Proteins ; DNA-Binding Proteins/genetics/*physiology ; Genes, Plant/physiology ; Plant Proteins/genetics/*physiology ; Transcription Factors ; }, abstract = {Multicellular organisms are composed of groups of different cell types. The importance in the evolution of cellular diversity of regulatory changes in genes that control cell specification has been revealed by a recent study of developmental genes in Arabidopsis.}, } @article {pmid11544353, year = {2001}, author = {Miller, MB and Bassler, BL}, title = {Quorum sensing in bacteria.}, journal = {Annual review of microbiology}, volume = {55}, number = {}, pages = {165-199}, doi = {10.1146/annurev.micro.55.1.165}, pmid = {11544353}, issn = {0066-4227}, mesh = {4-Butyrolactone/*analogs & derivatives/physiology ; Bacterial Proteins/physiology ; Gene Expression Regulation ; Gram-Negative Bacteria/pathogenicity/*physiology ; Gram-Positive Bacteria/pathogenicity/*physiology ; Oligopeptides/physiology ; Repressor Proteins/physiology ; Signal Transduction ; Trans-Activators/physiology ; Transcription Factors/physiology ; Virulence ; }, abstract = {Quorum sensing is the regulation of gene expression in response to fluctuations in cell-population density. Quorum sensing bacteria produce and release chemical signal molecules called autoinducers that increase in concentration as a function of cell density. The detection of a minimal threshold stimulatory concentration of an autoinducer leads to an alteration in gene expression. Gram-positive and Gram-negative bacteria use quorum sensing communication circuits to regulate a diverse array of physiological activities. These processes include symbiosis, virulence, competence, conjugation, antibiotic production, motility, sporulation, and biofilm formation. In general, Gram-negative bacteria use acylated homoserine lactones as autoinducers, and Gram-positive bacteria use processed oligo-peptides to communicate. Recent advances in the field indicate that cell-cell communication via autoinducers occurs both within and between bacterial species. Furthermore, there is mounting data suggesting that bacterial autoinducers elicit specific responses from host organisms. Although the nature of the chemical signals, the signal relay mechanisms, and the target genes controlled by bacterial quorum sensing systems differ, in every case the ability to communicate with one another allows bacteria to coordinate the gene expression, and therefore the behavior, of the entire community. Presumably, this process bestows upon bacteria some of the qualities of higher organisms. The evolution of quorum sensing systems in bacteria could, therefore, have been one of the early steps in the development of multicellularity.}, } @article {pmid11529427, year = {2001}, author = {Keeney, S}, title = {Mechanism and control of meiotic recombination initiation.}, journal = {Current topics in developmental biology}, volume = {52}, number = {}, pages = {1-53}, doi = {10.1016/s0070-2153(01)52008-6}, pmid = {11529427}, issn = {0070-2153}, mesh = {Amino Acid Sequence ; Animals ; Biological Evolution ; Chromosomes/metabolism ; Endodeoxyribonucleases/genetics/metabolism ; Esterases/genetics/metabolism ; Genes, Fungal ; Humans ; Meiosis/*physiology ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Structure, Tertiary ; RNA-Binding Proteins/genetics/metabolism ; *Recombination, Genetic ; Saccharomyces cerevisiae/*genetics/physiology ; }, abstract = {Homologous recombination is essential during meiosis in most sexually reproducing organisms. In budding yeast, and most likely in other organisms as well, meiotic recombination proceeds via the formation and repair of DNA double-strand breaks (DSBs). These breaks appear to be formed by the Spo11 protein, with assistance from a large number of other gene products, by a topoisomerase-like transesterase mechanism. Recent studies in fission yeast, multicellular fungi, flies, worms, plants, and mammals indicate that the role of Spo11 in meiotic recombination initiation is highly conserved. This chapter reviews the properties of Spo11 and the other gene products required for meiotic DSB formation in a number of organisms and discusses ways in which recombination initiation is coordinated with other events occurring in the meiotic cell.}, } @article {pmid11519173, year = {2001}, author = {Wada, H}, title = {[Evo-devo of multicellular animals: four evolutionary steps to vertebrates].}, journal = {Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme}, volume = {46}, number = {10}, pages = {1340-1348}, pmid = {11519173}, issn = {0039-9450}, mesh = {Animals ; Body Patterning/genetics ; *Evolution, Molecular ; Gene Duplication ; Genes, Homeobox ; *Vertebrates/embryology ; }, } @article {pmid11519171, year = {2001}, author = {Inouye, I}, title = {[Evolution from unicellular to multicellular organisms].}, journal = {Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme}, volume = {46}, number = {10}, pages = {1324-1331}, pmid = {11519171}, issn = {0039-9450}, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation ; *Cell Division ; Cell Membrane/physiology ; Cell Wall/physiology ; Humans ; Photosynthesis ; Plant Cells ; Signal Transduction ; }, } @article {pmid11516343, year = {2001}, author = {Verhagen, AM and Coulson, EJ and Vaux, DL}, title = {Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs.}, journal = {Genome biology}, volume = {2}, number = {7}, pages = {REVIEWS3009}, pmid = {11516343}, issn = {1474-760X}, mesh = {Amino Acid Sequence ; Animals ; Apoptosis/genetics/physiology ; Caspase Inhibitors ; Caspases/metabolism ; Chromosomal Proteins, Non-Histone/genetics/physiology ; Humans ; Inhibitor of Apoptosis Proteins ; Insect Proteins/*genetics/physiology ; *Microtubule-Associated Proteins ; Molecular Sequence Data ; Neoplasm Proteins ; Phylogeny ; Proteins/*genetics/physiology ; Sequence Homology, Amino Acid ; Survivin ; X-Linked Inhibitor of Apoptosis Protein ; }, abstract = {Apoptosis is a physiological cell death process important for development, homeostasis and the immune defence of multicellular animals. The key effectors of apoptosis are caspases, cysteine proteases that cleave after aspartate residues. The inhibitor of apoptosis (IAP) family of proteins prevent cell death by binding to and inhibiting active caspases and are negatively regulated by IAP-binding proteins, such as the mammalian protein DIABLO/Smac. IAPs are characterized by the presence of one to three domains known as baculoviral IAP repeat (BIR) domains and many also have a RING-finger domain at their carboxyl terminus. More recently, a second group of BIR-domain-containing proteins (BIRPs) have been identified that includes the mammalian proteins Bruce and Survivin as well as BIR-containing proteins in yeasts and Caenorhabditis elegans. These Survivin-like BIRPs regulate cytokinesis and mitotic spindle formation. In this review, we describe the IAPs and other BIRPs, their evolutionary relationships and their subcellular and tissue localizations.}, } @article {pmid11508852, year = {2001}, author = {Crichton, RR and Pierre, JL}, title = {Old iron, young copper: from Mars to Venus.}, journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}, volume = {14}, number = {2}, pages = {99-112}, doi = {10.1023/a:1016710810701}, pmid = {11508852}, issn = {0966-0844}, mesh = {Animals ; Biological Evolution ; Copper/chemistry/*metabolism ; Evolution, Chemical ; Humans ; Iron/chemistry/*metabolism ; Metalloproteins/chemistry/genetics/*metabolism ; Models, Biological ; Molecular Chaperones/chemistry/metabolism ; Oxidation-Reduction ; Saccharomyces cerevisiae/chemistry/*physiology ; }, abstract = {Iron and copper are metals which play an important role in the living world. From a brief consideration of their chemistry and biochemistry we conclude that the early chemistry of life used water soluble ferrous iron while copper was in the water-insoluble Cu(I) state as highly insoluble sulphides. The advent of oxygen was a catastrophic event for most living organisms, and can be considered to be the first general irreversible pollution of the earth. In contrast to the oxidation of iron and its loss of bioavailability as insoluble Fe(III), the oxidation of insoluble Cu(I) led to soluble Cu(II). A new iron biochemistry became possible after the advent of oxygen, with the development of chelators of Fe(III), which rendered iron once again accessible, and with the control of the potential toxicity of iron by its storage in a water soluble, non-toxic, bio-available storage protein (ferritin). Biology also discovered that whereas enzymes involved in anaerobic metabolism were designed to operate in the lower portion of the redox spectrum, the arrival of dioxygen created the need for a new redox active metal which could attain higher redox potentials. Copper, now bioavailable, was ideally suited to exploit the oxidizing power of dioxygen. The arrival of copper also coincided with the development of multicellular organisms which had extracellular cross-linked matrices capable of resisting attack by oxygen free radicals. After the initial 'iron age' subsequent evolution moved, not towards a 'copper age', but rather to an 'iron-copper' age. In the second part of the review, this symbiosis of iron and copper is examined in yeast. We then briefly consider iron and copper metabolism in mammals, before looking at iron-copper interactions in mammals, particularly man, and conclude with the reflection that, as in Greek and Roman mythology, a better understanding of the potentially positive interactions between Mars (iron) and Venus (copper) can only be to the advantage of our species.}, } @article {pmid11504843, year = {2001}, author = {Mattick, JS and Gagen, MJ}, title = {The evolution of controlled multitasked gene networks: the role of introns and other noncoding RNAs in the development of complex organisms.}, journal = {Molecular biology and evolution}, volume = {18}, number = {9}, pages = {1611-1630}, doi = {10.1093/oxfordjournals.molbev.a003951}, pmid = {11504843}, issn = {0737-4038}, mesh = {Animals ; *Evolution, Molecular ; Gene Expression Regulation/*genetics ; Humans ; Introns/genetics/physiology ; RNA, Untranslated/genetics/physiology ; }, abstract = {Eukaryotic phenotypic diversity arises from multitasking of a core proteome of limited size. Multitasking is routine in computers, as well as in other sophisticated information systems, and requires multiple inputs and outputs to control and integrate network activity. Higher eukaryotes have a mosaic gene structure with a dual output, mRNA (protein-coding) sequences and introns, which are released from the pre-mRNA by posttranscriptional processing. Introns have been enormously successful as a class of sequences and comprise up to 95% of the primary transcripts of protein-coding genes in mammals. In addition, many other transcripts (perhaps more than half) do not encode proteins at all, but appear both to be developmentally regulated and to have genetic function. We suggest that these RNAs (eRNAs) have evolved to function as endogenous network control molecules which enable direct gene-gene communication and multitasking of eukaryotic genomes. Analysis of a range of complex genetic phenomena in which RNA is involved or implicated, including co-suppression, transgene silencing, RNA interference, imprinting, methylation, and transvection, suggests that a higher-order regulatory system based on RNA signals operates in the higher eukaryotes and involves chromatin remodeling as well as other RNA-DNA, RNA-RNA, and RNA-protein interactions. The evolution of densely connected gene networks would be expected to result in a relatively stable core proteome due to the multiple reuse of components, implying that cellular differentiation and phenotypic variation in the higher eukaryotes results primarily from variation in the control architecture. Thus, network integration and multitasking using trans-acting RNA molecules produced in parallel with protein-coding sequences may underpin both the evolution of developmentally sophisticated multicellular organisms and the rapid expansion of phenotypic complexity into uncontested environments such as those initiated in the Cambrian radiation and those seen after major extinction events.}, } @article {pmid11500941, year = {2001}, author = {Martelli, AM and Zweyer, M and Ochs, RL and Tazzari, PL and Tabellini, G and Narducci, P and Bortul, R}, title = {Nuclear apoptotic changes: an overview.}, journal = {Journal of cellular biochemistry}, volume = {82}, number = {4}, pages = {634-646}, doi = {10.1002/jcb.1186}, pmid = {11500941}, issn = {0730-2312}, mesh = {*Apoptosis ; Autoantigens/immunology ; Autoimmunity ; Cell Nucleolus/ultrastructure ; Cell Nucleus/metabolism/*ultrastructure ; Humans ; Lipid Metabolism ; Necrosis ; Nuclear Matrix/ultrastructure ; Nuclear Proteins/immunology/metabolism ; Protein Processing, Post-Translational ; Signal Transduction ; }, abstract = {Apoptosis is a form of active cell death essential for morphogenesis, development, differentiation, and homeostasis of multicellular organisms. The activation of genetically controlled specific pathways that are highly conserved during evolution results in the characteristic morphological features of apoptosis that are mainly evident in the nucleus. These include chromatin condensation, nuclear shrinkage, and the formation of apoptotic bodies. The morphological changes are the result of molecular alterations, such as DNA and RNA cleavage, post-translational modifications of nuclear proteins, and proteolysis of several polypeptides residing in the nucleus. During the last five years our understanding of the process of apoptosis has dramatically increased. However, the mechanisms that lead to apoptotic changes in the nucleus have been only partially clarified. Here, we shall review the most recent findings that may explain why the nucleus displays these striking modifications. Moreover, we shall take into consideration the emerging evidence about apoptotic events as a trigger for the generation of autoantibodies to nuclear components.}, } @article {pmid11498045, year = {2001}, author = {Breakefield, XO and Kamm, C and Hanson, PI}, title = {TorsinA: movement at many levels.}, journal = {Neuron}, volume = {31}, number = {1}, pages = {9-12}, doi = {10.1016/s0896-6273(01)00350-6}, pmid = {11498045}, issn = {0896-6273}, mesh = {Animals ; Carrier Proteins/chemistry/*genetics/metabolism ; Dystonia Musculorum Deformans/*genetics/physiopathology ; Humans ; Models, Molecular ; *Molecular Chaperones ; Multigene Family ; Phylogeny ; Protein Conformation ; Sequence Deletion ; }, abstract = {TorsinA is the causative protein in the human neurologic disease early onset torsin dystonia, a movement disorder involving dysfunction in the basal ganglia without apparent neurodegeneration. Most cases result from a dominantly acting three-base pair deletion in the TOR1A gene causing loss of a glutamic acid near the carboxyl terminus of torsinA. Torsins are members of the AAA(+) superfamily of ATPases and are present in all multicellular organisms. Initial studies suggest that torsinA is an ER protein involved in chaperone functions and/or membrane movement.}, } @article {pmid11483989, year = {2001}, author = {Méchali, M}, title = {DNA replication origins: from sequence specificity to epigenetics.}, journal = {Nature reviews. Genetics}, volume = {2}, number = {8}, pages = {640-645}, doi = {10.1038/35084598}, pmid = {11483989}, issn = {1471-0056}, mesh = {Animals ; Bacteria/genetics ; Base Sequence ; DNA Replication/genetics ; Humans ; Models, Genetic ; Replication Origin/*genetics ; Replicon/genetics ; Yeasts/genetics ; }, abstract = {Site-specific initiation of DNA replication is a conserved function in all organisms. In Escherichia coli and Saccharomyces cerevisiae, DNA replication origins are sequence specific, but in multicellular organisms, origins are not so clearly defined. In this article, I present a model of origin specification by epigenetic mechanisms that allows the establishment of stable chromatin domains, which are characterized by autonomous replication. According to this model, origins of DNA replication help to establish domains of gene expression for the generation of cell diversity.}, } @article {pmid11481037, year = {2001}, author = {Ohkouchi, S and Nishio, K and Maeda, M and Hitomi, K and Adachi, H and Maki, M}, title = {Identification and characterization of two penta-EF-hand Ca(2+)-binding proteins in Dictyostelium discoideum.}, journal = {Journal of biochemistry}, volume = {130}, number = {2}, pages = {207-215}, doi = {10.1093/oxfordjournals.jbchem.a002974}, pmid = {11481037}, issn = {0021-924X}, mesh = {Amino Acid Sequence ; Animals ; Calcium/metabolism ; Calcium-Binding Proteins/*chemistry/classification/genetics/*metabolism ; Cell Fractionation ; Dictyostelium/*chemistry/genetics ; *EF Hand Motifs ; Gene Expression Regulation, Developmental ; In Situ Hybridization ; Molecular Sequence Data ; Phylogeny ; Protozoan Proteins/chemistry/classification/genetics/metabolism ; Sequence Alignment ; }, abstract = {Penta-EF-hand (PEF) proteins such as ALG-2 (apoptosis-linked gene 2 product) and the calpain small subunit are a newly classified family of Ca(2+)-binding proteins that possess five EF-hand-like motifs. We identified two mutually homologous PEF proteins, designated DdPEF-1 and DdPEF-2 (64% amino acid residue identities), in the cellular slime mold Dictyostelium discoideum. Both PEF proteins showed a higher similarity to mammalian ALG-2 and peflin (Group I PEF proteins) than to calpain and sorcin subfamily (Group II PEF proteins) in the first EF-hand (EF-1) regions. Northern blot analyses revealed that DdPEF-1 and DdPEF-2 were constitutively expressed throughout development of Dictyostelium, but their levels of expression were developmentally regulated. In situ hybridization analyses demonstrated that DdPEF-1 was expressed in both the anterior prestalk and the posterior prespore regions of the tipped aggregate, slugs and early culminants. On the other hand, DdPEF-2 was dominantly expressed in the anterior tip region of these multicellular structures. Both PEF proteins were detected as 22-23-kDa proteins in soluble fractions in the presence of EGTA but in particulate fractions in the presence of Ca(2+) by Western blotting using specific monoclonal antibodies. Together with the finding of PEF-like sequences in DNA databases of plants, fungi and protists, our results strongly suggest that Group I PEF proteins are ubiquitously present in all eukaryotes and play important roles in basic cellular functions.}, } @article {pmid11471456, year = {2001}, author = {Misevic, GN}, title = {Atomic force microscopy measurements. Measurements of binding strength between a single pair of molecules in physiological solutions.}, journal = {Molecular biotechnology}, volume = {18}, number = {2}, pages = {149-153}, pmid = {11471456}, issn = {1073-6085}, mesh = {Animals ; Biomechanical Phenomena ; Cell Adhesion ; Cell Adhesion Molecules/*metabolism ; Microscopy, Atomic Force/instrumentation/*methods ; Porifera/*metabolism ; Protein Binding ; Proteoglycans/metabolism ; Solutions ; Static Electricity ; }, abstract = {Atomic force microscopy (AFM) measurements of intermolecular binding strength between a single pair of complementary cell adhesion molecules in physiological solutions provided the first quantitative evidence for their cohesive function. This novel AFM based nanobiotechnology opens a molecular mechanic approach for studying structure to function related properties of any type of individual biological macromolecules. The presented example of Porifera cell adhesion glyconectin proteoglycans showed that homotypic carbohydrate to carbohydrate interactions between two primordial proteoglycans can hold the weight of 1600 cells. Thus, glyconectin type carbohydrates, as the most peripheral cell surface molecules of sponges (today's simplest living Metazoa), are proposed to be the primary cell adhesive molecules essential for the evolution of the multicellularity.}, } @article {pmid11461030, year = {2001}, author = {DosReis, GA and Barcinski, MA}, title = {Apoptosis and parasitism: from the parasite to the host immune response.}, journal = {Advances in parasitology}, volume = {49}, number = {}, pages = {133-161}, doi = {10.1016/s0065-308x(01)49039-7}, pmid = {11461030}, issn = {0065-308X}, mesh = {Animals ; Apoptosis/*immunology ; Eukaryota/*growth & development/immunology ; Host-Parasite Interactions/immunology ; Humans ; Protozoan Infections/*immunology/parasitology ; }, abstract = {Apoptosis, a form of programmed cell death (PCD), plays a central role in normal tissue development as well as in the pathogenesis of different diseases. PCD is responsible for the non-inflammatory physiological elimination of potentially harmful or unnecessary cells during embryogenesis, and for the proper functioning of continuous cell renewal systems in adult organisms. Maturation of the immune system and the specific immune response are examples of situations where PCD plays important roles. This review discusses the importance of apoptosis in two fundamental elements of a host-parasite interaction: the parasite (Section 1), and the host's immune response (Section 2). Section 1 discusses questions raised by the description of apoptosis in unicellular eukaryotes, such as the evolutionary origin of the molecular components of PCD, its role in the emergence and maintenance of parasitism, and the constraints of a multicellular organization for the proper operation of a cell death programme. The proposal is that PCD can occur in any situation where living cells display features of an organized network which operates through interactions within themselves and/or with elements of their environment. The possibility is also discussed that evolutionary relics of a complete cell death system may operate in unicellular parasites with functions other than inducing cell death. Section 2 reviews data on the mechanisms of host-cell PCD and the consequences of this phenomenon in host defence and pathogenesis. Infectious agents, from viruses to parasites, can either delay or induce apoptosis of different types of host cells. Apoptosis following lymphocyte polyclonal activation and stimulation of peripheral T lymphocytes, as a result of the engagement of specific counter-receptor systems, is of special interest for defining host immunocompetence and mechanisms of immunopathology.}, } @article {pmid11457908, year = {2001}, author = {Boyer, JS}, title = {Growth-induced water potentials originate from wall yielding during growth.}, journal = {Journal of experimental botany}, volume = {52}, number = {360}, pages = {1483-1488}, doi = {10.1093/jexbot/52.360.1483}, pmid = {11457908}, issn = {0022-0957}, mesh = {Adaptation, Physiological ; Cell Wall/physiology ; Hydrostatic Pressure ; Osmotic Pressure ; Plant Roots/physiology ; Plant Stems/physiology ; Soybeans/*growth & development ; *Water ; }, abstract = {Multicellular plants display growth-induced water potentials that generate tensions on water in the apoplast and move water into the growing cells. The potentials are sometimes assumed to arise from wall yielding, keeping the turgor pressure below what otherwise would occur. There has been no direct test of this theory, and therefore whole plants or growing regions of stems (hypocotyls) of dark-grown soybean (Glycine max L. Merr.) seedlings were sealed in a pressure chamber, and wall yielding was decreased by applying external pressure. In whole plants, external pressure had little effect because the plants and water supply were uniformly exposed to the pressure. If pressure was applied to the stem while the roots were outside in water, stem elongation was markedly inhibited because the pressure raised the water potential of the growing region and decreased water entry, reducing wall yielding. Further increasing the pressure prevented water entry completely and measured the tensions in the apoplast in the same growing regions. Tensions were about 0.19 MPa at low external pressure, but diminished as wall yielding was inhibited. At external pressures of about 0.63 MPa, wall yielding was abolished and tensions approached zero. There was a linear relation between wall yielding and tension, supporting the theory that wall yielding lowers the turgor thus causing most of the growth-induced water potential.}, } @article {pmid11455968, year = {2001}, author = {White, MK and McCubrey, JA}, title = {Suppression of apoptosis: role in cell growth and neoplasia.}, journal = {Leukemia}, volume = {15}, number = {7}, pages = {1011-1021}, doi = {10.1038/sj.leu.2402143}, pmid = {11455968}, issn = {0887-6924}, support = {CA51025/CA/NCI NIH HHS/United States ; DK45718/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Apoptosis ; Caspases/physiology ; Cell Division ; Enzyme Activation ; Humans ; NF-kappa B/physiology ; Neoplasms/*etiology ; Phosphatidylinositol 3-Kinases/physiology ; Proto-Oncogene Proteins c-bcl-2/physiology ; }, abstract = {A cell is a potentially dangerous thing. In unicellular organisms, cells divide and multiply in a manner that is chiefly determined by the availability of nutritional substrates. In a multicellular organism, each cell has a distinct growth potential that is designed to subsume a role in the function of the whole body. Departure from this path to one of uncontrolled cellular proliferation leads to cancer. For this reason, evolution has endowed cells with an elaborate set of systems that cause errant cells to self-destruct. This process of cell suicide is known as apoptosis or programmed cell death and it plays a crucial role in the growth of both normal and malignant cells. In this review, we describe the mechanisms whereby programmed cell death is induced and executed. In particular, we concentrate on how anti-apoptotic signals generated by cytokines promote cell survival and how these signal transduction pathways may be involved in the pathogenesis of neoplasia. Understanding how these processes contribute to tumorigenesis may suggest new therapeutic options.}, } @article {pmid11438670, year = {2001}, author = {Krause, SA and Loupart, ML and Vass, S and Schoenfelder, S and Harrison, S and Heck, MM}, title = {Loss of cell cycle checkpoint control in Drosophila Rfc4 mutants.}, journal = {Molecular and cellular biology}, volume = {21}, number = {15}, pages = {5156-5168}, pmid = {11438670}, issn = {0270-7306}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Alleles ; Amino Acid Sequence ; Animals ; Bromodeoxyuridine/metabolism ; Cell Cycle ; Cell Nucleus/metabolism ; Cells, Cultured ; Chromosome Aberrations ; Chromosome Disorders ; Chromosomes/metabolism/ultrastructure ; Cloning, Molecular ; DNA/metabolism ; DNA-Binding Proteins/*genetics ; Drosophila/metabolism ; Indoles/metabolism ; Larva/metabolism ; Microscopy, Fluorescence ; Mitosis ; Molecular Sequence Data ; *Mutation ; Phylogeny ; Polymerase Chain Reaction ; Replication Protein C ; Salivary Glands/metabolism ; Sequence Homology, Amino Acid ; }, abstract = {Two alleles of the Drosophila melanogaster Rfc4 (DmRfc4) gene, which encodes subunit 4 of the replication factor C (RFC) complex, cause striking defects in mitotic chromosome cohesion and condensation. These mutations produce larval phenotypes consistent with a role in DNA replication but also result in mitotic chromosomal defects appearing either as premature chromosome condensation-like or precocious sister chromatid separation figures. Though the DmRFC4 protein localizes to all replicating nuclei, it is dispersed from chromatin in mitosis. Thus the mitotic defects appear not to be the result of a direct role for RFC4 in chromosome structure. We also show that the mitotic defects in these two DmRfc4 alleles are the result of aberrant checkpoint control in response to DNA replication inhibition or damage to chromosomes. Not all surveillance function is compromised in these mutants, as the kinetochore attachment checkpoint is operative. Intriguingly, metaphase delay is frequently observed with the more severe of the two alleles, indicating that subsequent chromosome segregation may be inhibited. This is the first demonstration that subunit 4 of RFC functions in checkpoint control in any organism, and our findings additionally emphasize the conserved nature of RFC's involvement in checkpoint control in multicellular eukaryotes.}, } @article {pmid11435126, year = {2001}, author = {McFall-Ngai, MJ}, title = {Identifying 'prime suspects': symbioses and the evolution of multicellularity.}, journal = {Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology}, volume = {129}, number = {4}, pages = {711-723}, doi = {10.1016/s1096-4959(01)00406-7}, pmid = {11435126}, issn = {1096-4959}, mesh = {Animals ; Bacteria/genetics ; Bacterial Physiological Phenomena ; *Biological Evolution ; *Evolution, Molecular ; Genes, Plant ; Signal Transduction ; *Symbiosis ; }, abstract = {The possible involvement of symbioses in the evolution of multicellularity is explored. Evidence is drawn principally from the biology of present day associations of plants and animals with prokaryotes. A particular emphasis is placed on future research opportunities in this area of biology that have been provided by the advent of specific molecular techniques and new model systems. With the application of new approaches that result from these advances, a more holistic understanding of the biology of the coevolved communities, composed of animals or plants and their associated prokaryotes, is within the reach of biologists over the next few decades.}, } @article {pmid11428464, year = {2001}, author = {Marais, G and Duret, L}, title = {Synonymous codon usage, accuracy of translation, and gene length in Caenorhabditis elegans.}, journal = {Journal of molecular evolution}, volume = {52}, number = {3}, pages = {275-280}, doi = {10.1007/s002390010155}, pmid = {11428464}, issn = {0022-2844}, mesh = {Animals ; Caenorhabditis elegans/*genetics ; Codon/*genetics ; Humans ; *Protein Biosynthesis ; Regression Analysis ; }, abstract = {In many unicellular organisms, invertebrates, and plants, synonymous codon usage biases result from a coadaptation between codon usage and tRNAs abundance to optimize the efficiency of protein synthesis. However, it remains unclear whether natural selection acts at the level of the speed or the accuracy of mRNAs translation. Here we show that codon usage can improve the fidelity of protein synthesis in multicellular species. As predicted by the model of selection for translational accuracy, we find that the frequency of codons optimal for translation is significantly higher at codons encoding for conserved amino acids than at codons encoding for nonconserved amino acids in 548 genes compared between Caenorhabditis elegans and Homo sapiens. Although this model predicts that codon bias correlates positively with gene length, a negative correlation between codon bias and gene length has been observed in eukaryotes. This suggests that selection for fidelity of protein synthesis is not the main factor responsible for codon biases. The relationship between codon bias and gene length remains unexplained. Exploring the differences in gene expression process in eukaryotes and prokaryotes should provide new insights to understand this key question of codon usage.}, } @article {pmid11423315, year = {2001}, author = {Müller, WE}, title = {Review: How was metazoan threshold crossed? The hypothetical Urmetazoa.}, journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology}, volume = {129}, number = {2-3}, pages = {433-460}, doi = {10.1016/s1095-6433(00)00360-3}, pmid = {11423315}, issn = {1095-6433}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Cell Adhesion Molecules/physiology ; Germ Cells/physiology ; Invertebrates/*physiology ; Molecular Sequence Data ; Morphogenesis ; Porifera/immunology/physiology ; Sequence Homology, Amino Acid ; *Signal Transduction ; }, abstract = {The origin of Metazoa remained--until recently--the most enigmatic of all phylogenetic problems. Sponges [Porifera] as "living fossils", positioned at the base of multicellular animals, have been used to answer basic questions in metazoan evolution by molecular biological techniques. During the last few years, cDNAs/genes coding for informative proteins have been isolated and characterized from sponges, especially from the marine demosponges Suberites domuncula and Geodia cydonium. The analyses of their deduced amino acid sequences allowed a molecular biological resolution of the monophyly of Metazoa. Molecules of the extracellular matrix/basal lamina, with the integrin receptor, fibronectin and galectin as prominent examples, cell-surface receptors (tyrosine kinase receptors), elements of nerve system/sensory cells (metabotropic glutamate receptor), homologs/modules of an immune system [immunoglobulin-like molecules, SRCR- and SCR-repeats, cytokines, (2-5)A synthetase], as well as morphogens (myotrophin) classify the Porifera as true Metazoa. As "living fossils", provided with simple, primordial molecules allowing cell-cell and cell-matrix adhesion, as well as processes of signal transduction as known in a more complex manner from higher Metazoa, sponges also show peculiarities. Tissues of sponges are rich in telomerase activity, suggesting a high plasticity in the determination of cell lineages. It is concluded that molecular biological studies with sponges as models will not only help to understand the evolution to the Metazoa but also the complex, hierarchical regulatory network of cells in higher Metazoa [reviewed in Progress in Molecular Subcellular Biology, vols. 19, 21 (1998) Springer Verlag]. The hypothetical ancestral animal, the Urmetazoa, from which the metazoan lineages diverged (more than 600 MYA), may have had the following characteristics: cell adhesion molecules with intracellular signal transduction pathways, morphogens/growth factors forming gradients, a functional immune system, and a primordial nerve cell/receptor system.}, } @article {pmid11418856, year = {2001}, author = {Stanhope, MJ and Lupas, A and Italia, MJ and Koretke, KK and Volker, C and Brown, JR}, title = {Phylogenetic analyses do not support horizontal gene transfers from bacteria to vertebrates.}, journal = {Nature}, volume = {411}, number = {6840}, pages = {940-944}, doi = {10.1038/35082058}, pmid = {11418856}, issn = {0028-0836}, mesh = {Animals ; Evolution, Molecular ; Expressed Sequence Tags ; *Gene Transfer, Horizontal ; *Genes, Bacterial ; *Genome, Human ; Humans ; Phylogeny ; Polymerase Chain Reaction ; Vertebrates/genetics ; }, abstract = {Horizontal gene transfer (HGT) has long been recognized as a principal force in the evolution of genomes. Genome sequences of Archaea and Bacteria have revealed the existence of genes whose similarity to loci in distantly related organisms is explained most parsimoniously by HGT events. In most multicellular organisms, such genetic fixation can occur only in the germ line. Therefore, it is notable that the publication of the human genome reports 113 incidents of direct HGT between bacteria and vertebrates, without any apparent occurrence in evolutionary intermediates, that is, non-vertebrate eukaryotes. Phylogenetic analysis arguably provides the most objective approach for determining the occurrence and directionality of HGT. Here we report a phylogenetic analysis of 28 proposed HGT genes, whose presence in the human genome had been confirmed by polymerase chain reaction (PCR). The results indicate that most putative HGT genes are present in more anciently derived eukaryotes (many such sequences available in non-vertebrate EST databases) and can be explained in terms of descent through common ancestry. They are, therefore, unlikely to be examples of direct HGT from bacteria to vertebrates.}, } @article {pmid11409870, year = {2001}, author = {Serra, E and Ars, E and Ravella, A and Sánchez, A and Puig, S and Rosenbaum, T and Estivill, X and Lázaro, C}, title = {Somatic NF1 mutational spectrum in benign neurofibromas: mRNA splice defects are common among point mutations.}, journal = {Human genetics}, volume = {108}, number = {5}, pages = {416-429}, doi = {10.1007/s004390100514}, pmid = {11409870}, issn = {0340-6717}, mesh = {Alleles ; Base Sequence ; Chromosomes, Human, Pair 17/genetics ; DNA Mutational Analysis ; Exons/genetics ; Female ; Fibroblasts ; Genetic Markers/genetics ; Genotype ; Germ-Line Mutation/genetics ; Humans ; Loss of Heterozygosity/*genetics ; Male ; Nerve Tissue Proteins/*genetics ; Neurofibroma/*genetics/pathology ; Neurofibromatosis 1/*genetics/pathology ; Neurofibromin 1 ; Pedigree ; Point Mutation/*genetics ; Polymorphism, Single-Stranded Conformational ; RNA Splice Sites/*genetics ; RNA Splicing/genetics ; RNA, Messenger/genetics/metabolism ; }, abstract = {Neurofibromas, benign tumors that originate from the peripheral nerve sheath, are a hallmark of neurofibromatosis type 1 (NF1). Although loss of heterozygosity (LOH) is a common phenomenon in this neoplasia, it only accounts for part of the somatic NF1 mutations found. Somatic point mutations or the presence of "two hits" in the NF1 gene have only been reported for a few neurofibromas. The large size of the NF1 gene together with the multicellular composition of these tumors has greatly hampered their molecular characterization. Here, we present the somatic NF1 mutational analysis of the whole set of neurofibromas studied by our group and consisting in 126 tumors derived from 32 NF1 patients. We report the identification of 45 independent somatic NF1 mutations, 20 of which are reported for the first time. Different types of point mutations together with LOH affecting the NF1 gene and its surrounding region or extending along the 17q arm have been found. Among point mutations, those affecting the correct splicing of the NF1 gene are common, coinciding with results reported on germline NF1 mutations. In most cases, we have been able to confirm that both copies of the NF1 gene are inactivated. We have also found that both somatic and germline mutations can be expressed at the RNA level in the neoplastic cells. Furthermore, we have observed that the study of more than one tumor derived from the same patient is useful for the identification of the germline mutation. Finally, we have noticed that the culture of neurofibromas and their fibroblast clearance facilitates LOH detection in cases in which it is difficult to determine.}, } @article {pmid11405100, year = {2001}, author = {Goodwin, TJ and Ormandy, JE and Poulter, RT}, title = {L1-like non-LTR retrotransposons in the yeast Candida albicans.}, journal = {Current genetics}, volume = {39}, number = {2}, pages = {83-91}, doi = {10.1007/s002940000181}, pmid = {11405100}, issn = {0172-8083}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Northern ; Blotting, Southern ; Candida albicans/*genetics ; Conserved Sequence ; DNA/genetics/isolation & purification ; Evolution, Molecular ; Gene Dosage ; Long Interspersed Nucleotide Elements/*genetics ; Open Reading Frames/genetics ; Phylogeny ; Sequence Alignment ; Sequence Analysis, DNA ; Time ; Trans-Activators ; Transcription, Genetic/*genetics ; Transcriptional Activation/*genetics ; }, abstract = {Non-LTR retrotransposons (also known as LINEs) have had a major influence on the structure of many eukaryote genomes. They are abundant in many multicellular eukaryotes, including mammals, but appear to be absent from the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. This absence has, to date, precluded the development of a yeast model system for the study of non-LTR retrotransposons. In this report we describe several families of non-LTR retrotransposons from the yeast Candida albicans. These elements, which we call Zorro elements, are all members of the L1 clade of non-LTR retrotransposons. Some are intact, transcriptionally active and have transposed recently. This finding should allow the development of a yeast model system.}, } @article {pmid11408580, year = {2001}, author = {Matyash, V and Geier, C and Henske, A and Mukherjee, S and Hirsh, D and Thiele, C and Grant, B and Maxfield, FR and Kurzchalia, TV}, title = {Distribution and transport of cholesterol in Caenorhabditis elegans.}, journal = {Molecular biology of the cell}, volume = {12}, number = {6}, pages = {1725-1736}, pmid = {11408580}, issn = {1059-1524}, support = {F32 GM019167-01/GM/NIGMS NIH HHS/United States ; F32 GM019167-02/GM/NIGMS NIH HHS/United States ; R01 DK027083/DK/NIDDK NIH HHS/United States ; F32 GM019167/GM/NIGMS NIH HHS/United States ; DK-27083/DK/NIDDK NIH HHS/United States ; R37 DK027083/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Biological Transport ; Caenorhabditis elegans/*metabolism ; Cholesterol/*metabolism ; Digestive System/metabolism ; *Egg Proteins ; Electrophoresis, Polyacrylamide Gel ; Endocytosis ; Ergosterol/analogs & derivatives/metabolism/pharmacokinetics ; Female ; Male ; Microscopy, Fluorescence ; Models, Chemical ; Mutation ; Octoxynol ; Pharynx/metabolism ; Polyethylene Glycols/pharmacology ; Precipitin Tests ; Receptors, Cell Surface/metabolism ; Spermatids/metabolism ; Spermatocidal Agents/pharmacology ; Spermatozoa/*metabolism ; Sterols/metabolism ; Sucrose/metabolism ; Ultraviolet Rays ; Vitellogenins/metabolism ; }, abstract = {Cholesterol transport is an essential process in all multicellular organisms. In this study we applied two recently developed approaches to investigate the distribution and molecular mechanisms of cholesterol transport in Caenorhabditis elegans. The distribution of cholesterol in living worms was studied by imaging its fluorescent analog, dehydroergosterol, which we applied to the animals by feeding. Dehydroergosterol accumulates primarily in the pharynx, nerve ring, excretory gland cell, and gut of L1-L3 larvae. Later, the bulk of dehydroergosterol accumulates in oocytes and spermatozoa. Males display exceptionally strong labeling of spermatids, which suggests a possible role for cholesterol in sperm development. In a complementary approach, we used a photoactivatable cholesterol analog to identify cholesterol-binding proteins in C. elegans. Three major and several minor proteins were found specifically cross-linked to photocholesterol after UV irradiation. The major proteins were identified as vitellogenins. rme-2 mutants, which lack the vitellogenin receptor, fail to accumulate dehydroergosterol in oocytes and embryos and instead accumulate dehydroergosterol in the body cavity along with vitellogenin. Thus, uptake of cholesterol by C. elegans oocytes occurs via an endocytotic pathway involving yolk proteins. The pathway is a likely evolutionary ancestor of mammalian cholesterol transport.}, } @article {pmid11399629, year = {2000}, author = {Armeanu, S and MÜller, CA and Klein, G}, title = {Involvement of E-cadherin in the Development of Erythroid Cells; Subject Heading.}, journal = {Hematology (Amsterdam, Netherlands)}, volume = {5}, number = {4}, pages = {307-316}, doi = {10.1080/10245332.2000.11746524}, pmid = {11399629}, issn = {1607-8454}, abstract = {The cadherins represent a large family of structurally and functionally related cell adhesion molecules involved in morphogenesis of multicellular organisms and maintenance of solid tissues. In the hematopoietic system, however, almost nothing was known about the involvement of this family. PCR screening of RNA of human bone marrow mononuclear cells with specific primers for different classical cadherins revealed that members of this family are also expressed by bone marrow cells. Here we report that E-cadherin, which is mainly expressed by cells of epithelial origin, plays a critical role in the development of human erythrocytes. FACS analysis with human E-cadherin-specific antibodies and the use of immunoaffinity columns revealed that expression of E-cadherin is restricted to defined maturation stages of the erythropoietic cell lineage. Erythroblasts and normoblasts express E-cadherin, but mature erythrocytes do not. Lymphoid and all the other myeloid cell lineages do not express E-cadherin at any developmental stage. The differentiation of the erythroid lineage in vitro could be influenced by addition of anti-E-cadherin antibodies in a concentration dependent manner indicating a direct involvement of this cell adhesion molecule in the differentiation process. In line with these in vitro data is the finding that E-cadherin is down regulated during erythroleukemia on the developing erythroid cells. Our results suggest an unanticipated function of E-cadherin in the hematopoietic system.}, } @article {pmid11352464, year = {2001}, author = {Halperin, T and Zheng, B and Itzhaki, H and Clarke, AK and Adam, Z}, title = {Plant mitochondria contain proteolytic and regulatory subunits of the ATP-dependent Clp protease.}, journal = {Plant molecular biology}, volume = {45}, number = {4}, pages = {461-468}, pmid = {11352464}, issn = {0167-4412}, mesh = {ATPases Associated with Diverse Cellular Activities ; Adenosine Triphosphatases/*genetics/metabolism ; Amino Acid Sequence ; Arabidopsis/enzymology/*genetics ; *Bacterial Proteins ; Caseins/metabolism ; DNA, Complementary/chemistry/genetics ; Endopeptidase Clp ; Escherichia coli Proteins ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Plant ; Mitochondria/*enzymology/metabolism ; Molecular Chaperones ; Molecular Sequence Data ; Phylogeny ; Protein Subunits ; RNA, Messenger/genetics/metabolism ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Serine Endopeptidases/metabolism ; Tissue Distribution ; }, abstract = {The proteolytic machinery of plant organelles is largely unknown, although indications so far point to several proteases of bacterial origin. In this study an Arabidopsis thaliana cDNA was isolated that encodes a homologue of bacterial ClpX, a molecular chaperone and regulatory subunit of the ATP-dependent, serine-type Clp protease. Computer analysis of the predicted plant ClpX revealed a putative mitochondrial transit peptide at the N-terminus, as well as overall sequence similarity to other eukaryotic ClpX homologues. Specific polyclonal antibodies were made to the Arabidopsis ClpX protein and used to confirm its localization in plant mitochondria. In addition to ClpX, a ClpP protein located in mitochondria was also identified from the numerous ClpP isomers in Arabidopsis. Localization of this nuclear-encoded protein, termed ClpP2, was determined first by its close sequence similarity to mitochondrial ClpP human, and later experimentally using ClpP2-specific antibodies with isolated plant organellar fractions. In Arabidopsis, transcripts for both clpX and clpP2 genes were detected in various tissues and under different growth conditions, with no significant variation in mRNA level (i.e. 2-fold) for each gene between samples. Using beta-casein as a substrate, plant mitochondria were found to possess an ATP-stimulated, serine-type proteolytic activity that could be strongly inhibited by antibodies specific for ClpX or ClpP2, suggesting an active ClpXP protease. The recent discovery of homologous mitochondrial ClpX and ClpP proteins in mammals suggests that this type of protease may be common to multicellular eukaryotes.}, } @article {pmid11348582, year = {2000}, author = {Furusawa, C and Kaneko, K}, title = {Complex organization in multicellularity as a necessity in evolution.}, journal = {Artificial life}, volume = {6}, number = {4}, pages = {265-281}, doi = {10.1162/106454600300103638}, pmid = {11348582}, issn = {1064-5462}, mesh = {*Biological Evolution ; *Cell Communication ; Cell Death ; Cell Differentiation/*physiology ; Cell Division/physiology ; *Cell Physiological Phenomena ; Growth ; *Models, Biological ; Stem Cells/physiology ; }, abstract = {By introducing a dynamical system model of a multicellular system, it is shown that an organism with a variety of differentiated cell types and a complex pattern emerges through cell-cell interactions even without postulating any elaborate control mechanism. Such an organism is found to maintain a larger growth speed as an ensemble, by achieving a cooperative use of resources, than do simple homogeneous cells, which behave "selfishly." This suggests that the emergence of multicellular organisms with complex organization is a necessity in evolution. According to our theoretical model, there initially appear multipotent stem cells, which undergo stochastic differentiation to other cell types. With development and differentiation, both the chemical diversity and the complexity of intra-cellular dynamics are decreased, as a general consequence of our system. Robustness of the developmental process is also confirmed.}, } @article {pmid11346875, year = {2001}, author = {Nangia, R and Sait, SN and Block, AW and Zhang, PJ}, title = {Trisomy 6 in basal cell carcinomas correlates with metastatic potential: a dual color fluorescence in situ hybridization study on paraffin sections.}, journal = {Cancer}, volume = {91}, number = {10}, pages = {1927-1932}, doi = {10.1002/1097-0142(20010515)91:10<1927::aid-cncr1215>3.0.co;2-r}, pmid = {11346875}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Basal Cell/genetics/*secondary ; Chromosome Aberrations/genetics ; Chromosomes, Human, Pair 6/*genetics ; Female ; Genetic Markers ; Humans ; In Situ Hybridization, Fluorescence/methods ; Karyotyping ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Skin Neoplasms/genetics/*pathology ; *Trisomy ; }, abstract = {BACKGROUND: Most basal cell carcinomas (BCCs) are indolent lesions; a few become locally aggressive or even metastatic. Little is known about the molecular and genetic alterations in this malignant transformation. Conventional karyotyping in BCC has revealed a high frequency of nonclonal, structural rearrangements, with few cases that show multiple, unrelated, small clones suggestive of a multicellular origin. Trisomy 6 was described recently in a few BCCs, but the biologic significance of the appearance of trisomy 6 in BBCs was not clear.

METHODS: Thirty cases including 4 metastatic, 4 locally aggressive, and 22 conventional nonaggressive BCCs were studied. Fluorescence in situ hybridization (FISH) was performed on 4 microm tissue sections, using alpha-centromeric enumeration probes for chromosome 6 (SpectrumGreen, Vysis Inc., Downers Grove, IL) and chromosome 4 (SpectrumOrange, Vysis Inc., Downers Grove, IL, used as disomic cell control). Trisomy 6 was semiquantitated within tumor cells and nonneoplastic cells in each case.

RESULTS: Trisomy 6 was identified in all 4 metastatic BCCs within tumor cells and in corresponding BCCs at the primary cutaneous site in 2 of these 4 cases. Two locally aggressive BCCs, 1 of which had preceding radiation exposure, also showed trisomy 6. All nonaggressive BCCs and nonneoplastic cells were disomic for chromosome 6.

CONCLUSIONS: Trisomy 6 has been identified as a cytogenetic aberration representative of tumor cells in aggressive and metastatic BCC. None of the nonaggressive BCCs in this study demonstrated trisomy 6. Acquisition of trisomy 6 by tumor cells in BCC may lead to the emergence of metastatic potential. Additional studies to define the underlying mechanisms may be valuable in preventing aggressive behavior in BCC.}, } @article {pmid11346655, year = {2001}, author = {Sánchez-Fernández, R and Davies, TG and Coleman, JO and Rea, PA}, title = {The Arabidopsis thaliana ABC protein superfamily, a complete inventory.}, journal = {The Journal of biological chemistry}, volume = {276}, number = {32}, pages = {30231-30244}, doi = {10.1074/jbc.M103104200}, pmid = {11346655}, issn = {0021-9258}, mesh = {ATP-Binding Cassette Transporters/*chemistry/metabolism ; Algorithms ; Arabidopsis/*chemistry/*genetics ; Binding Sites ; DNA, Complementary/metabolism ; Databases, Factual ; Expressed Sequence Tags ; Models, Genetic ; Multigene Family ; Mutation ; Open Reading Frames ; Phylogeny ; Plant Proteins/*chemistry ; Protein Binding ; Protein Structure, Tertiary ; }, abstract = {We describe the first complete inventory of ATP-binding cassette (ABC) proteins from a multicellular organism, the model plant Arabidopsis thaliana. By the application of several search criteria, Arabidopsis was found to contain a total of 129 open reading frames (ORFs) capable of encoding ABC proteins, of which 103 possessed contiguous transmembrane spans and were identified as putative intrinsic membrane proteins. Fifty-two of the putative intrinsic membrane proteins contained at least two transmembrane domains (TMDs) and two nucleotide-binding folds (NBFs) and could be classified as belonging to one of five subfamilies of full-molecule transporters. The other 51 putative membrane proteins, all of which were half-molecule transporters, fell into five subfamilies. Of the remaining ORFs identified, all of which encoded proteins lacking TMDs, 11 could be classified into three subfamilies. There were no obvious homologs in other organisms for 15 of the ORFs which encoded a heterogeneous group of non-intrinsic ABC proteins (NAPs). Unrooted phylogenetic analyses substantiated the subfamily designations. Notable features of the Arabidopsis ABC superfamily was the presence of a large yeast-like PDR subfamily, and the absence of genes encoding bona fide cystic fibrosis transmembrane conductance regulator (CFTR), sulfonylurea receptor (SUR), and heavy metal tolerance factor 1 (HMT1) homologs. Arabidopsis was unusual in its large allocation of ORFs (a minimum of 0.5%) to members of the ABC protein superfamily.}, } @article {pmid11341677, year = {2001}, author = {Salazar-Ciudad, I and Newman, SA and Solé, RV}, title = {Phenotypic and dynamical transitions in model genetic networks. I. Emergence of patterns and genotype-phenotype relationships.}, journal = {Evolution & development}, volume = {3}, number = {2}, pages = {84-94}, doi = {10.1046/j.1525-142x.2001.003002084.x}, pmid = {11341677}, issn = {1520-541X}, mesh = {Biological Evolution ; Genotype ; Likelihood Functions ; *Models, Genetic ; *Phenotype ; }, abstract = {Genotype-phenotype interactions during the evolution of form in multicellular organisms is a complex problem but one that can be aided by computational approaches. We present here a framework within which developmental patterns and their underlying genetic networks can be simulated. Gene networks were chosen to reflect realistic regulatory circuits, including positive and negative feedback control, and the exchange of a subset of gene products between cells, or within a syncytium. Some of these networks generate stable spatial patterns of a subset of their molecular constituents, and can be assigned to categories (e.g., "emergent" or "hierarchic") based on the topology of molecular circuitry. These categories roughly correspond to what has been discussed in the literature as "self-organizing" and "programmed" processes of development. The capability of such networks to form patterns of repeating stripes was studied in network ensembles in which parameters of gene-gene interaction were caused to vary in a manner analogous to genetic mutation. The evolution under mutational change of individual representative networks of each category was also simulated. We have found that patterns with few stripes (< or =3) are most likely to originate in the form of a hierarchic network, whereas those with greater numbers of stripes (> or =4) originate most readily as emergent networks. However, regardless of how many stripes it contains, once a pattern is established, there appears to be an evolutionary tendency for emergent mechanisms to be replaced by hierarchic mechanisms. These results have potential significance for the understanding of genotype-phenotype relationships in the evolution of metazoan form.}, } @article {pmid11340380, year = {2001}, author = {Pogány, G and Timár, F and Oláh, J and Harisi, R and Polony, G and Paku, S and Bocsi, J and Jeney, A and Laurie, GW}, title = {Role of the basement membrane in tumor cell dormancy and cytotoxic resistance.}, journal = {Oncology}, volume = {60}, number = {3}, pages = {274-281}, doi = {10.1159/000055329}, pmid = {11340380}, issn = {0030-2414}, support = {R01 EY009747-08/EY/NEI NIH HHS/United States ; }, mesh = {Cell Division ; Cell Survival/drug effects/radiation effects ; Doxorubicin/pharmacology ; Drug Resistance, Neoplasm ; Extracellular Matrix/*physiology ; Humans ; Neoplasms/drug therapy/*pathology ; Tumor Cells, Cultured ; }, abstract = {OBJECTIVES AND METHODS: Tumor dormancy and resistance to cytotoxic agents are key limiting events in the treatment of malignant diseases. To determine whether both are influenced by the extracellular milieu in which tumors reside, HT1080 human fibrosarcoma, MCF-7 breast carcinoma and OSCORT osteosarcoma cell proliferation, viability, apoptosis and cytoreductive-treatment-induced death were investigated in the presence or absence of extracellular matrix (ECM).

RESULTS: ECM-adherent, but not plastic-adherent HT1080 cells formed a multicellular network accompanied by reduced proliferation and lowered DNA synthetic capacity. The number of cells in S-phase was dramatically reduced. Viable cells entered a state of dormancy reminiscent of that observed in the step of metastasis after extravasation, i.e. prior to the initiation of progressive growth. Such ECM-induced dormancy could be reversed by plating cells on plastic, but only after a 48-hour lag period. No difference was indicated in clonogenicity of HT1080 cells originated from plastic or ECM gel. However, the cells released from ECM gel showed significantly reduced migration ability. The resistance of anchored cells against cytotoxic damage was increased by ECM gel. Examination of cytoreductive treatment revealed that ECM adherence at the time of injury is partially protective, a property which was also moderately apparent when injured cells were transferred to the basement membrane.

CONCLUSIONS: Taken together, these results suggest that the ECM plays a key role in tumor dormancy and cytotoxic resistance, both explorable at the molecular level using our in vitro model system.}, } @article {pmid11328851, year = {2001}, author = {Vitt, UA and Hsu, SY and Hsueh, AJ}, title = {Evolution and classification of cystine knot-containing hormones and related extracellular signaling molecules.}, journal = {Molecular endocrinology (Baltimore, Md.)}, volume = {15}, number = {5}, pages = {681-694}, doi = {10.1210/mend.15.5.0639}, pmid = {11328851}, issn = {0888-8809}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Cystine/*chemistry ; Hormones/*chemistry ; Humans ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Tertiary ; Sequence Alignment ; Sequence Homology, Amino Acid ; Signal Transduction ; }, abstract = {The cystine knot three-dimensional structure is found in many extracellular molecules and is conserved among divergent species. The identification of proteins with a cystine knot structure is difficult by commonly used pairwise alignments because the sequence homology among these proteins is low. Taking advantage of complete genome sequences in diverse organisms, we used a complementary approach of pattern searches and pairwise alignments to screen the predicted protein sequences of five model species (human, fly, worm, slime mold, and yeast) and retrieved proteins with low sequence homology but containing a typical cystine knot signature. Sequence comparison between proteins known to have a cystine knot three-dimensional structure (transforming growth factor-beta, glycoprotein hormone, and platelet-derived growth factor subfamily members) identified new crucial amino acid residues (two hydrophilic amino acid residues flanking cysteine 5 of the cystine knot). In addition to the well known members of the cystine knot superfamily, novel subfamilies of proteins (mucins, norrie disease protein, von Willebrand factor, bone morphogenetic protein antagonists, and slit-like proteins) were identified as putative cystine knot-containing proteins. Phylogenetic analysis revealed the ancient evolution of these proteins and the relationship between hormones [e.g. transforming growth factor-beta (TGFbeta)] and extracellular matrix proteins (e.g. mucins). They are absent in the unicellular yeast genome but present in nematode, fly, and higher species, indicating that the cystine knot structure evolved in extracellular signaling molecules of multicellular organisms. All data retrieved by this study can be viewed at http://hormone.stanford.edu/.}, } @article {pmid11321585, year = {2001}, author = {Ueki, T and Inouye, S}, title = {SigB, SigC, and SigE from Myxococcus xanthus homologous to sigma32 are not required for heat shock response but for multicellular differentiation.}, journal = {Journal of molecular microbiology and biotechnology}, volume = {3}, number = {2}, pages = {287-293}, pmid = {11321585}, issn = {1464-1801}, support = {GM26843/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Bacterial Proteins/biosynthesis/chemistry/*genetics ; Base Sequence ; Conserved Sequence ; *DNA-Binding Proteins ; Gene Deletion ; *Gene Expression Regulation, Bacterial ; Gene Expression Regulation, Developmental ; Heat-Shock Proteins/chemistry/*genetics ; Hot Temperature ; Molecular Sequence Data ; Myxococcus xanthus/genetics/growth & development/*physiology ; Open Reading Frames ; Phylogeny ; Sequence Alignment ; Sequence Homology, Amino Acid ; Sigma Factor/biosynthesis/chemistry/*genetics ; Transcription Factors/chemistry/*genetics ; }, abstract = {Myxococcus xanthus has been known to have multiple sigma factors which are considered to play important roles in regulation of gene expression in development. A new gene encoding a putative sigma factor, sigE, was cloned by using a degenerate oligonucleotide corresponding to the conserved region 2.2 of M. xanthus SigA. In the 2.0-kb nucleotide sequence, an open reading frame consisting of 280 amino acid residues was identified. The amino acid sequence of SigE shows high similarity to heat shock sigma factors in bacteria. However, the sigE gene is not induced by heat shock and deletion of sigE does not affect production of heat shock proteins. SigE is expressed during both vegetative growth and fruiting body development. In the deletion mutant of the sigE gene fruiting body formation is initiated earlier and fewer spores are produced than in the parent strain. Interestingly, the deltasigE mutant shows defects in fruiting body formation at 37 degrees C. In addition to SigE, SigB and SigC show high sequence similarity to heat shock sigma factors. However, even if all three sigma factor genes are disrupted, heat shock proteins are still normally induced. A deltasigBdeltasigCdeltasigE triple deletion strain forms fruiting bodies earlier, but sporulats later than the parent strain. Spores from the triple deletion mutant are aberrant and their viability is less than 0.001% compared with that of the parent strain, suggesting that these sigma factors may have redundant functions in multicellular differentiation of M. xanthus.}, } @article {pmid11298810, year = {2001}, author = {Michod, RE and Roze, D}, title = {Cooperation and conflict in the evolution of multicellularity.}, journal = {Heredity}, volume = {86}, number = {Pt 1}, pages = {1-7}, doi = {10.1046/j.1365-2540.2001.00808.x}, pmid = {11298810}, issn = {0018-067X}, mesh = {Animals ; *Biological Evolution ; Humans ; *Models, Biological ; }, abstract = {Multicellular organisms probably originated as groups of cells formed in several ways, including cell proliferation from a group of founder cells and aggregation. Cooperation among cells benefits the group, but may be costly (altruistic) or beneficial (synergistic) to individual cooperating cells. In this paper, we study conflict mediation, the process by which genetic modifiers evolve that enhance cooperation by altering the parameters of development or rules of formation of cell groups. We are particularly interested in the conditions under which these modifiers lead to a new higher-level unit of selection with increased cooperation among group members and heritable variation in fitness at the group level. By sculpting the fitness variation and opportunity for selection at the two levels, conflict modifiers create new functions at the organism level. An organism is more than a group of cooperating cells related by common descent; organisms require adaptations that regulate conflict within. Otherwise their continued evolution is frustrated by the creation of within-organism variation and conflict between levels of selection. The evolution of conflict modifiers is a necessary prerequisite to the emergence of individuality and the continued well being of the organism. Conflict leads--through the evolution of adaptations that reduce i--to greater individuality and harmony for the organism.}, } @article {pmid11290293, year = {2001}, author = {Lee, MM and Schiefelbein, J}, title = {Developmentally distinct MYB genes encode functionally equivalent proteins in Arabidopsis.}, journal = {Development (Cambridge, England)}, volume = {128}, number = {9}, pages = {1539-1546}, doi = {10.1242/dev.128.9.1539}, pmid = {11290293}, issn = {0950-1991}, mesh = {Amino Acid Sequence ; Arabidopsis/cytology/*genetics/growth & development ; *Arabidopsis Proteins ; DNA-Binding Proteins/*genetics ; *Genes, Plant ; *Genes, myb ; Genetic Complementation Test ; Hypocotyl/cytology ; Molecular Sequence Data ; Plant Proteins/*genetics ; Plant Roots/cytology ; *Protozoan Proteins ; Sequence Homology, Amino Acid ; Transcription Factors/genetics ; Transcriptional Activation ; }, abstract = {The duplication and divergence of developmental control genes is thought to have driven morphological diversification during the evolution of multicellular organisms. To examine the molecular basis of this process, we analyzed the functional relationship between two paralogous MYB transcription factor genes, WEREWOLF (WER) and GLABROUS1 (GL1), in Arabidopsis. The WER and GL1 genes specify distinct cell types and exhibit non-overlapping expression patterns during Arabidopsis development. Nevertheless, reciprocal complementation experiments with a series of gene fusions showed that WER and GL1 encode functionally equivalent proteins, and their unique roles in plant development are entirely due to differences in their cis-regulatory sequences. Similar experiments with a distantly related MYB gene (MYB2) showed that its product cannot functionally substitute for WER or GL1. Furthermore, an analysis of the WER and GL1 proteins shows that conserved sequences correspond to specific functional domains. These results provide new insights into the evolution of the MYB gene family in Arabidopsis, and, more generally, they demonstrate that novel developmental gene function may arise solely by the modification of cis-regulatory sequences.}, } @article {pmid11283698, year = {2001}, author = {Kimbrell, DA and Beutler, B}, title = {The evolution and genetics of innate immunity.}, journal = {Nature reviews. Genetics}, volume = {2}, number = {4}, pages = {256-267}, doi = {10.1038/35066006}, pmid = {11283698}, issn = {1471-0056}, mesh = {Animals ; Apoptosis ; *Biological Evolution ; Drosophila/genetics/*immunology/microbiology ; *Drosophila Proteins ; Humans ; Immunity, Innate/*genetics/*immunology ; Infections/immunology ; Insect Proteins/genetics/*immunology ; Interleukin-1/chemistry/genetics/immunology ; Membrane Glycoproteins/genetics/*immunology ; Phylogeny ; Receptors, Cell Surface/genetics/immunology ; Signal Transduction ; Toll-Like Receptor 5 ; Toll-Like Receptors ; }, abstract = {The immune system provides protection from a wide range of pathogens. One component of immunity, the phylogenetically ancient innate immune response, fights infections from the moment of first contact and is the fundamental defensive weapon of multicellular organisms. The Toll family of receptors has a crucial role in immune defence. Studies in fruitflies and in mammals reveal that the defensive strategies of invertebrates and vertebrates are highly conserved at the molecular level, which raises the exciting prospects of an increased understanding of innate immunity.}, } @article {pmid11283359, year = {2001}, author = {Cox, E and Bonner, J}, title = {Ecology. The advantages of togetherness.}, journal = {Science (New York, N.Y.)}, volume = {292}, number = {5516}, pages = {448-449}, doi = {10.1126/science.1060456}, pmid = {11283359}, issn = {0036-8075}, mesh = {Adenosine Triphosphate/*metabolism ; Biological Evolution ; Carbohydrate Metabolism ; Diffusion ; *Fermentation ; Mathematics ; *Models, Biological ; Mucor/cytology/metabolism ; Myxococcales/cytology/physiology ; Myxomycetes/cytology/physiology ; *Oxygen Consumption ; Thermodynamics ; }, abstract = {What would be the advantage of unicellular organisms becoming multicellular? For organisms that feed on organic food (heterotrophs), the most efficient way to produce energy is to metabolize the food by aerobic respiration, but the fastest way is to metabolize it by fermentation. In their Perspective, Cox and Bonner discuss a mathematical model (Pfeiffer et al.), which shows that when these two kinds of organisms (respirators and fermenters) compete for a limited food source, the respirators manage best when they are grouped in clusters rather than remaining as separate cells. In this way, multicellularity could have originated.}, } @article {pmid11283355, year = {2001}, author = {Pfeiffer, T and Schuster, S and Bonhoeffer, S}, title = {Cooperation and competition in the evolution of ATP-producing pathways.}, journal = {Science (New York, N.Y.)}, volume = {292}, number = {5516}, pages = {504-507}, doi = {10.1126/science.1058079}, pmid = {11283355}, issn = {0036-8075}, mesh = {Adenosine Triphosphate/*metabolism ; Animals ; Bacteria/growth & development/metabolism ; *Biological Evolution ; Carbohydrate Metabolism ; Dictyostelium/growth & development/metabolism ; Energy Metabolism ; *Fermentation ; Fungi/growth & development/metabolism ; Mathematics ; *Models, Biological ; Oxidation-Reduction ; Oxidative Phosphorylation ; *Oxygen Consumption ; Thermodynamics ; }, abstract = {Heterotrophic organisms generally face a trade-off between rate and yield of adenosine triphosphate (ATP) production. This trade-off may result in an evolutionary dilemma, because cells with a higher rate but lower yield of ATP production may gain a selective advantage when competing for shared energy resources. Using an analysis of model simulations and biochemical observations, we show that ATP production with a low rate and high yield can be viewed as a form of cooperative resource use and may evolve in spatially structured environments. Furthermore, we argue that the high ATP yield of respiration may have facilitated the evolutionary transition from unicellular to undifferentiated multicellular organisms.}, } @article {pmid11252632, year = {2001}, author = {Busch, A and Schumacher, U and Storch, V}, title = {Histochemistry of lectin-binding sites in Halicryptus spinulosus (Priapulida).}, journal = {Acta histochemica}, volume = {103}, number = {1}, pages = {9-19}, doi = {10.1078/0065-1281-00574}, pmid = {11252632}, issn = {0065-1281}, mesh = {Acetylgalactosamine/analysis/*metabolism ; Acetylglucosamine/analysis/*metabolism ; Animals ; Biological Evolution ; *Carbohydrate Metabolism ; Carbohydrates/analysis ; Fucose/analysis/metabolism ; Glycoconjugates/*metabolism ; Glycosylation ; Histocytochemistry/*methods ; Invertebrates ; Lectins/*chemistry ; N-Acetylneuraminic Acid/analysis/*metabolism ; Phylogeny ; Staining and Labeling/*methods ; }, abstract = {Priapulida represent one of the phylogenetically oldest multicellular animal groups. In multicellular animals (Metazoa) cell-to-cell and cell-to-matrix interactions are often mediated by carbohydrate residues of glycoconjugates. To analyze the carbohydrate composition of a phylogenetically old species, lectin histochemistry was employed on 5 specimens of the priapulid Halicryptus spinulosus. Many lectins bound to the chitin-containing cuticle, including those specific for carbohydrates other than N-acetylglucosamine, the principle building block of chitin. The connective tissue of the animals contained both N-acetylglucosamine and N-acetylgalactosamine. Mannose residues were widely distributed with the exception of the cuticle, but complex type carbohydrates were not present in the entire animal. Sialic acid residues were only detected in the cuticle and brush border of the intestinal epithelium, while fucose was limited to the cuticle. Thus, the lectin-binding pattern indicated that sugars typical for the linking region of both N- and O-glycoproteins in mammals are also present in H. spinulosus. Carbohydrate residues that are typical for the complex type of N-linked glycans in vertebrates are not present as are carbohydrate residues typical for the termination of O-linked carbohydrate chains. Hence, a truncated form of both N- and O-linked glycosylation is present in H. spinulosus indicating that more complex patterns of glycosylation developed later during evolution.}, } @article {pmid11250149, year = {2001}, author = {Brogiolo, W and Stocker, H and Ikeya, T and Rintelen, F and Fernandez, R and Hafen, E}, title = {An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control.}, journal = {Current biology : CB}, volume = {11}, number = {4}, pages = {213-221}, doi = {10.1016/s0960-9822(01)00068-9}, pmid = {11250149}, issn = {0960-9822}, mesh = {Amino Acid Sequence ; Amino Acids ; Animals ; Animals, Genetically Modified ; Binding Sites ; Cell Count ; Cell Division ; Cell Size ; Conserved Sequence/*physiology ; Drosophila/genetics/*growth & development/metabolism ; *Evolution, Molecular ; Gene Expression ; Gene Expression Regulation ; Genes, Insect ; Humans ; Insect Proteins/genetics/metabolism/*physiology ; Insulin/genetics/metabolism/*physiology ; Molecular Sequence Data ; Mutagenesis ; Peptides/genetics/metabolism/*physiology ; Receptor Protein-Tyrosine Kinases/genetics/metabolism/physiology ; Receptor, IGF Type 1/genetics/metabolism/*physiology ; Receptor, Insulin/genetics/metabolism/*physiology ; }, abstract = {BACKGROUND: Size regulation is fundamental in developing multicellular organisms and occurs through the control of cell number and cell size. Studies in Drosophila have identified an evolutionarily conserved signaling pathway that regulates organismal size and that includes the Drosophila insulin receptor substrate homolog Chico, the lipid kinase PI(3)K (Dp110), DAkt1/dPKB, and dS6K.

RESULTS: We demonstrate that varying the activity of the Drosophila insulin receptor homolog (DInr) during development regulates organ size by changing cell size and cell number in a cell-autonomous manner. An amino acid substitution at the corresponding position in the kinase domain of the human and Drosophila insulin receptors causes severe growth retardation. Furthermore, we show that the Drosophila genome contains seven insulin-like genes that are expressed in a highly tissue- and stage-specific pattern. Overexpression of one of these insulin-like genes alters growth control in a DInr-dependent manner.

CONCLUSIONS: This study shows that the Drosophila insulin receptor autonomously controls cell and organ size, and that overexpression of a gene encoding an insulin-like peptide is sufficient to increase body size.}, } @article {pmid11250079, year = {2001}, author = {Huizing, M and Didier, A and Walenta, J and Anikster, Y and Gahl, WA and Krämer, H}, title = {Molecular cloning and characterization of human VPS18, VPS 11, VPS16, and VPS33.}, journal = {Gene}, volume = {264}, number = {2}, pages = {241-247}, doi = {10.1016/s0378-1119(01)00333-x}, pmid = {11250079}, issn = {0378-1119}, support = {R01 EY010199/EY/NEI NIH HHS/United States ; EY10199/EY/NEI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Blotting, Northern ; Carrier Proteins/*genetics ; DNA, Complementary/chemistry/genetics ; Female ; Humans ; Membrane Proteins/*genetics ; Molecular Sequence Data ; Phylogeny ; Proteins/*genetics ; RNA, Messenger/genetics/metabolism ; Sequence Analysis, DNA ; Tissue Distribution ; *Vesicular Transport Proteins ; }, abstract = {In multicellular organisms, the delivery of proteins to lysosomes is essential. Many of the genes necessary for this process have first been identified by their requirement for vacuolar delivery in yeast. A subset of these genes, the four class C vps genes, is necessary for the delivery of endocytic and biosynthetic cargo in yeast, and also in Drosophila. Here, we describe the sequence and expression pattern of four human homologs of these genes. This initial molecular description of these four genes is an important step towards their evaluation as candidate genes that may be involved in the pathogenesis of Hermansky-Pudlak syndrome-related diseases.}, } @article {pmid11216836, year = {2001}, author = {Indrianto, A and Barinova, I and Touraev, A and Heberle-Bors, E}, title = {Tracking individual wheat microspores in vitro: identification of embryogenic microspores and body axis formation in the embryo.}, journal = {Planta}, volume = {212}, number = {2}, pages = {163-174}, doi = {10.1007/s004250000375}, pmid = {11216836}, issn = {0032-0935}, mesh = {Seeds/growth & development/*ultrastructure ; Spores/*ultrastructure ; Triticum/*embryology ; }, abstract = {The development of isolated, defined wheat microspores undergoing in vitro embryogenesis has been followed by cell tracking. Isolated wheat (Triticum aestivum L.). microspores were immobilized in Sea Plaque agarose supported by a polypropylene mesh at a low cell density and cultured in a hormone-free, maltose-containing medium in the presence of ovaries serving as a conditioning factor. Embryogenesis was followed in microspores isolated from immature anthers of freshly cut tillers or from heat- and starvation-treated, excised anthers. Three types of microspore were identified on the basis of their cytological features at the start of culture. Type- microspores had a big central vacuole and a nucleus close to the microspore wall, usually opposite to the germ pore. This type was identical to the late microspore stage in anthers developing in vivo. Microspores with a fragmented vacuole and a peripheral cytoplasmic pocket containing the nucleus were defined as type 2. In type-3 microspores the nucleus was positioned in a cytoplasmic pocket in the centre of the microspore. Tracking revealed that, irrespective of origin, type-1 microspores first developed into type 2 and then into type-3 microspores. After a few more days, type-3 microspores absorbed their vacuoles and differentiated into cytoplasm-rich and starch-accumulating cells, which then divided to form multicellular structures. Apparently the three types of microspore represent stages in a continuous process and not, as previously assumed, distinct classes of responding and non-responding microspores. The first cell division of the embryogenic microspores was always symmetric. Cell tracking also revealed that the original microspore wall opened opposite to a region in the multicellular microspore which consisted of cells containing starch grains while the remaining cells were starch grain-free. The starch-containing cells were located close to the germ pore of the microspore. In more advanced embryos the broken microspore wall was detected at the root pole of the embryo.}, } @article {pmid11214901, year = {2001}, author = {Fuchs, T and Glusman, G and Horn-Saban, S and Lancet, D and Pilpel, Y}, title = {The human olfactory subgenome: from sequence to structure and evolution.}, journal = {Human genetics}, volume = {108}, number = {1}, pages = {1-13}, doi = {10.1007/s004390000436}, pmid = {11214901}, issn = {0340-6717}, mesh = {Amino Acid Sequence ; Animals ; Chromosome Mapping ; Databases as Topic ; *Evolution, Molecular ; Humans ; In Situ Hybridization, Fluorescence ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Protein Structure, Secondary ; Receptors, Odorant/*genetics ; Sequence Analysis, DNA ; }, abstract = {Olfactory receptors (ORs) constitute the largest multigene family in multicellular organisms. Their evolutionary proliferation has been driven by the need to provide recognition capacity for millions of potential odorants with arbitrary chemical configurations. Human genome sequencing has provided a highly informative picture of the "olfactory subgenome", the repertoire of OR genes. We describe here an analysis of 224 human OR genes, a much larger number than hitherto systematically analyzed. These are derived by literature survey, data mining at 14 genomic clusters, and by an OR-targeted experimental sequencing strategy. The presented set contains at least 53% pseudogenes and is minimally divided into 11 gene families. One of these (no. 7) has undergone a particularly extensive expansion in primates. The analysis of this collection leads to insight into the origin of OR genes, suggesting a graded expansion through mammalian evolution. It also allows us to delineate a structural map of the respective proteins. A sequence database and analysis package is provided (http://bioinformatics.weizmann.ac.il/HORDE), which will be useful for analyzing human OR sequences genome-wide.}, } @article {pmid11212539, year = {2000}, author = {Punin, MIu}, title = {[Intestinal regulatory systems in invertebrates and their evolution in multicellular animals].}, journal = {Zhurnal evoliutsionnoi biokhimii i fiziologii}, volume = {36}, number = {6}, pages = {586-599}, pmid = {11212539}, issn = {0044-4529}, mesh = {Animals ; *Biological Evolution ; Digestive System/cytology/innervation ; Digestive System Physiological Phenomena ; Endocrine System/cytology ; Epithelial Cells ; Invertebrates/*physiology ; }, } @article {pmid11199398, year = {2000}, author = {Lam, E and del Pozo, O}, title = {Caspase-like protease involvement in the control of plant cell death.}, journal = {Plant molecular biology}, volume = {44}, number = {3}, pages = {417-428}, pmid = {11199398}, issn = {0167-4412}, mesh = {*Apoptosis ; Caspases/*physiology ; Plant Cells ; Plants/*enzymology ; Signal Transduction ; }, abstract = {Cell death as a highly regulated process has now been recognized to be an important, if not essential, pathway that is ubiquitous in all multicellular eukaryotes. In addition to playing key roles in the morphogenesis and sculpting of the organs to give rise to highly specialized forms and shapes, cell death also participates in the programmed creation of specialized cell types for essential functions such as the selection of B cells in the immune system of mammals and the formation of tracheids in the xylem of vascular plants. Studies of apoptosis, the most well-characterized form of animal programmed cell death, have culminated in the identification of a central tripartite death switch the enzymatic component of which is a conserved family of cysteine proteases called caspases. Studies in invertebrates and other animal models suggest that caspases are conserved regulators of apoptotic cell death in all metazoans. In plant systems, the identities of the main executioners that orchestrate cell death remain elusive. Recent evidence from inhibitor studies and biochemical approaches suggests that caspase-like proteases may also be involved in cell death control in higher plants. Furthermore, the mitochondrion and reactive oxygen species may well constitute a common pathway for cell death activation in both animal and plant cells. Cloning of plant caspase-like proteases and elucidation of the mechanisms through which mitochondria may regulate cell death in both systems should shed light on the evolution of cell death control in eukaryotes and may help to identify essential components that are highly conserved in eukaryotes.}, } @article {pmid11179224, year = {2001}, author = {Plaza, S and Prince, F and Jaeger, J and Kloter, U and Flister, S and Benassayag, C and Cribbs, D and Gehring, WJ}, title = {Molecular basis for the inhibition of Drosophila eye development by Antennapedia.}, journal = {The EMBO journal}, volume = {20}, number = {4}, pages = {802-811}, pmid = {11179224}, issn = {0261-4189}, mesh = {Animals ; Antennapedia Homeodomain Protein ; Apoptosis ; Drosophila/*embryology/genetics ; Drosophila Proteins ; Embryonic Development ; Eye/cytology/*embryology ; Homeodomain Proteins/metabolism/*physiology ; *Nuclear Proteins ; Protein Binding ; *Transcription Factors ; }, abstract = {Hox genes encoding homeodomain transcriptional regulators are known to specify the body plan of multicellular organisms and are able to induce body plan transformations when misexpressed. These findings led to the hypothesis that duplication events and misexpression of Hox genes during evolution have been necessary for generating the observed morphological diversity found in metazoans. It is known that overexpressing Antennapedia (Antp) in the head induces antenna-to-leg as well as head-to-thorax transformation and eye reduction. At present, little is known about the exact molecular mechanism causing these phenotypes. The aim of this study is to understand the basis of inhibition of eye development. We demonstrate that Antp represses the activity of the eye regulatory cascade. By ectopic expression, we show that Antp antagonizes the activity of the eye selector gene eyeless. Using both in vitro and in vivo experiments, we demonstrate that this inhibitory mechanism involves direct protein-protein interactions between the DNA-binding domains of EY and ANTP, resulting in mutual inhibition.}, } @article {pmid11173114, year = {2001}, author = {Kondrashov, AS}, title = {Sex and U.}, journal = {Trends in genetics : TIG}, volume = {17}, number = {2}, pages = {75-77}, doi = {10.1016/s0168-9525(00)02188-0}, pmid = {11173114}, issn = {0168-9525}, mesh = {Animals ; Biological Evolution ; Humans ; *Mutation ; Phenotype ; *Sex Ratio ; }, abstract = {Resolution of several unsettled problems in genetics depends on the genomic rate of deleterious mutation, U. Selection against mutations can be a major factor in evolution only if U > or =1. Recently, significant progress has been made in measuring U in multicellular eukaryotes. An indirect estimate, based on a human-chimpanzee pseudogene comparison, produced U>3 for hominoids. By contrast, an estimate for Drosophila based on comparison of synonymous protein-coding sites produced U<0.1. However, the Drosophila figure might be underestimated because of selection at synonymous sites. Perhaps, the best way to measure U is to observe mutations shortly after they appear. So far, this direct approach has been applied only to humans and Caenorhabditis elegans, yielding high estimates of mutation rates.}, } @article {pmid11158292, year = {2001}, author = {Wu, J and Glass, NL}, title = {Identification of specificity determinants and generation of alleles with novel specificity at the het-c heterokaryon incompatibility locus of Neurospora crassa.}, journal = {Molecular and cellular biology}, volume = {21}, number = {4}, pages = {1045-1057}, pmid = {11158292}, issn = {0270-7306}, support = {R01 GM060468/GM/NIGMS NIH HHS/United States ; GM60468/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Amino Acid Sequence ; Base Sequence ; Chimera/genetics ; DNA Primers/genetics ; Fungal Proteins/chemistry/*genetics ; Genes, Fungal ; Genetic Variation ; Models, Biological ; Molecular Sequence Data ; Neurospora crassa/*genetics/growth & development ; Phenotype ; Phylogeny ; Protein Structure, Tertiary ; Transformation, Genetic ; }, abstract = {The capacity for nonself recognition is a ubiquitous and essential aspect of biology. In filamentous fungi, nonself recognition during vegetative growth is believed to be mediated by genetic differences at heterokaryon incompatibility (het) loci. Filamentous fungi are capable of undergoing hyphal fusion to form mycelial networks and with other individuals to form vegetative heterokaryons, in which genetically distinct nuclei occupy a common cytoplasm. In Neurospora crassa, 11 het loci have been identified that affect the viability of such vegetative heterokaryons. The het-c locus has at least three mutually incompatible alleles, termed het-c(OR), het-c(PA), and het-c(GR). Hyphal fusion between strains that are of alternative het-c specificity results in vegetative heterokaryons that are aconidial and which show growth inhibition and hyphal compartmentation and death. A 34- to 48-amino-acid variable domain, which is dissimilar in HET-C(OR), HET-C(PA), and HET-C(GR), confers allelic specificity. To assess requirements for allelic specificity, we constructed chimeras between the het-c variable domain from 24 different isolates that displayed amino acid and insertion or deletion variations and determined their het-c specificity by introduction into N. crassa. We also constructed a number of artificial alleles that contained novel het-c specificity domains. By this method, we identified four additional and novel het-c specificities. Our results indicate that amino acid and length variations within the insertion or deletion motif are the primary determinants for conferring het-c allelic specificity. These results provide a molecular model for nonself recognition in multicellular eucaryotes.}, } @article {pmid10754074, year = {2000}, author = {Ono-Koyanagi, K and Suga, H and Katoh, K and Miyata, T}, title = {Protein tyrosine phosphatases from amphioxus, hagfish, and ray: divergence of tissue-specific isoform genes in the early evolution of vertebrates.}, journal = {Journal of molecular evolution}, volume = {50}, number = {3}, pages = {302-311}, doi = {10.1007/s002399910035}, pmid = {10754074}, issn = {0022-2844}, mesh = {Animals ; Base Sequence ; Chordata, Nonvertebrate/enzymology/*genetics ; DNA Primers ; *Evolution, Molecular ; Hagfishes/*genetics ; Humans ; Isoenzymes/*genetics ; Molecular Sequence Data ; Phylogeny ; Protein Tyrosine Phosphatases/*genetics ; Skates, Fish/*genetics ; }, abstract = {Since separation from fungi and plants, multicellular animals evolved a variety of gene families involved in cell-cell communication from a limited number of ancestral precursors by gene duplications in two separate periods of animal evolution. In the very early evolution of animals before the separation of parazoans and eumetazoans, animals underwent extensive gene duplications by which different subtypes (subfamilies) with distinct functions diverged. The multiplicity of members (isoforms) in the same subtype increased by further gene duplications (isoform duplications) in the first half of chordate evolution before the fish-tetrapod split; different isoforms are virtually identical in structure and function but differ in tissue distribution. From cloning and phylogenetic analyses of four subfamilies of the protein tyrosine kinase (PTK) family, we recently showed extensive isoform duplications in a limited period around or just before the cyclostome-gnathostome split. To obtain a reliable estimate for the divergence time of vertebrate isoforms, we have conducted isolation of cDNAs encoding the protein tyrosine phosphatases (PTPs) from Branchiostoma belcheri, an amphioxus, Eptatretus burgeri, a hagfish, and Potamotrygon motoro, a ray. We obtained 33 different cDNAs in total, most of which belong to known PTP subfamilies. The phylogenetic analyses of five subfamilies based on the maximum likelihood method revealed frequent isoform duplications in a period around or just before the gnathostome-cyclostome split. An evolutionary implication was discussed in relation to the Cambrian explosion.}, } @article {pmid11149291, year = {2000}, author = {Jacksch, R and Schiele, TM and Knobloch, W and Niehues, R and Hauser, ER and Massalha, K}, title = {[Carotid stenting with the new slotted tube stent--prospective multicenter study. Essen experiences]].}, journal = {Zeitschrift fur Kardiologie}, volume = {89 Suppl 8}, number = {}, pages = {40-46}, pmid = {11149291}, issn = {0300-5860}, mesh = {Aged ; Carotid Stenosis/diagnosis/*therapy ; Equipment Design ; Female ; Germany ; Humans ; Ischemic Attack, Transient/diagnosis/therapy ; Male ; Middle Aged ; Prospective Studies ; *Stents ; Treatment Outcome ; }, abstract = {UNLABELLED: The indication for therapy of high degree carotid stenoses is discussed controversely in regard to new publications. Only symptomatic carotid stenoses are accepted as indication for operative therapy (arterectomy). The new method of carotid stenting was investigated in several studies and needs to be proved in controlled prospective randomized trials. The use of the self-expanding wall-stent has been established in most working groups; nevertheless some disadvantages should be considered (uncontrolled long segment stenting, covering the origin of ext. carotid artery, insufficient adaptation of struts in carotid communis). After development of a new flexible multicellular balloon-expanding stent (Jo-Carotisstent) with sufficient flexibility and compressibility and different stent lengths, the use of this stent in high degree carotid stenoses was investigated. The aim of this study was to analyze the acute and long-term quantitative stent results (angiography and duplex sonography) and clinical results periinterventionally and during follow-up (0.5-1 year).

METHODS: Selective approach from femoral, 8 Fr.-guiding catheter, canalization of stenosis with coronary guide wire (0.014 inch), primary PTA with coronary balloon.

RESULTS: In 47 of 48 patients with 49 carotid stenoses, successful stent implantation was achieved (97.9%). In 2 patients TIA of short duration (4.2%) and in 1 patient (2.1%) a minor stroke occurred. All stents could be implanted with optimal reference diameter. During follow up after 0.5 year no significant proliferative restenosis was observed. The quantitative analysis showed excellent stent-diameter after 0.5 year with only minimal recoil (< 5%) and no clinical event.

CONCLUSION: Using a new flexible and non-deforming multicellular balloon-expanded stent, selective stenting of high degree carotid artery stenoses can be realized with an excellent procedural success rate and a complication rate comparable with the results of other publicated studies. The results after 0.5 year follow-up seem to be promising.}, } @article {pmid11144279, year = {2000}, author = {Newman, SA and Müller, GB}, title = {Epigenetic mechanisms of character origination.}, journal = {The Journal of experimental zoology}, volume = {288}, number = {4}, pages = {304-317}, doi = {10.1002/1097-010X(20001215)288:4<304::AID-JEZ3>3.0.CO;2-G}, pmid = {11144279}, issn = {0022-104X}, mesh = {Animals ; *Biological Evolution ; Body Patterning/*genetics ; *Models, Genetic ; Phenotype ; }, abstract = {The close mapping between genotype and morphological phenotype in many contemporary metazoans has led to the general notion that the evolution of organismal form is a direct consequence of evolving genetic programs. In contrast to this view, we propose that the present relationship between genes and form is a highly derived condition, a product of evolution rather than its precondition. Prior to the biochemical canalization of developmental pathways, and the stabilization of phenotypes, interaction of multicellular organisms with their physicochemical environments dictated a many-to-many mapping between genomes and forms. These forms would have been generated by epigenetic mechanisms: initially physical processes characteristic of condensed, chemically active materials, and later conditional, inductive interactions among the organism's constituent tissues. This concept, that epigenetic mechanisms are the generative agents of morphological character origination, helps to explain findings that are difficult to reconcile with the standard neo-Darwinian model, e.g., the burst of body plans in the early Cambrian, the origins of morphological innovation, homology, and rapid change of form. Our concept entails a new interpretation of the relationship between genes and biological form.}, } @article {pmid11140681, year = {2000}, author = {Strassmann, JE and Zhu, Y and Queller, DC}, title = {Altruism and social cheating in the social amoeba Dictyostelium discoideum.}, journal = {Nature}, volume = {408}, number = {6815}, pages = {965-967}, doi = {10.1038/35050087}, pmid = {11140681}, issn = {0028-0836}, mesh = {Animals ; Biological Evolution ; Dictyostelium/genetics/*physiology ; Microsatellite Repeats ; Models, Biological ; Reproduction/physiology ; }, abstract = {The social amoeba, Dictyostelium discoideum, is widely used as a simple model organism for multicellular development, but its multicellular fruiting stage is really a society. Most of the time, D. discoideum lives as haploid, free-living, amoeboid cells that divide asexually. When starved, 10(4)-10(5) of these cells aggregate into a slug. The anterior 20% of the slug altruistically differentiates into a non-viable stalk, supporting the remaining cells, most of which become viable spores. If aggregating cells come from multiple clones, there should be selection for clones to exploit other clones by contributing less than their proportional share to the sterile stalk. Here we use microsatellite markers to show that different clones collected from a field population readily mix to form chimaeras. Half of the chimaeric mixtures show a clear cheater and victim. Thus, unlike the clonal and highly cooperative development of most multicellular organisms, the development of D. discoideum is partly competitive, with conflicts of interests among cells. These conflicts complicate the use of D. discoideum as a model for some aspects of development, but they make it highly attractive as a model system for social evolution.}, } @article {pmid11130711, year = {2000}, author = {, }, title = {Analysis of the genome sequence of the flowering plant Arabidopsis thaliana.}, journal = {Nature}, volume = {408}, number = {6814}, pages = {796-815}, doi = {10.1038/35048692}, pmid = {11130711}, issn = {0028-0836}, mesh = {Animals ; Arabidopsis/cytology/*genetics/growth & development/physiology ; Biological Transport ; Cell Membrane/metabolism ; Cell Nucleus/genetics ; Centromere ; Chloroplasts/genetics ; Chromosome Mapping ; DNA Repair ; DNA Transposable Elements ; DNA, Plant ; DNA, Ribosomal ; Gene Duplication ; Gene Expression Regulation, Plant ; *Genome, Plant ; Humans ; Light ; Mitochondria/genetics ; Photosynthesis ; Plant Diseases ; Proteome ; Recombination, Genetic ; Repetitive Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Signal Transduction ; Species Specificity ; Telomere ; }, abstract = {The flowering plant Arabidopsis thaliana is an important model system for identifying genes and determining their functions. Here we report the analysis of the genomic sequence of Arabidopsis. The sequenced regions cover 115.4 megabases of the 125-megabase genome and extend into centromeric regions. The evolution of Arabidopsis involved a whole-genome duplication, followed by subsequent gene loss and extensive local gene duplications, giving rise to a dynamic genome enriched by lateral gene transfer from a cyanobacterial-like ancestor of the plastid. The genome contains 25,498 genes encoding proteins from 11,000 families, similar to the functional diversity of Drosophila and Caenorhabditis elegans--the other sequenced multicellular eukaryotes. Arabidopsis has many families of new proteins but also lacks several common protein families, indicating that the sets of common proteins have undergone differential expansion and contraction in the three multicellular eukaryotes. This is the first complete genome sequence of a plant and provides the foundations for more comprehensive comparison of conserved processes in all eukaryotes, identifying a wide range of plant-specific gene functions and establishing rapid systematic ways to identify genes for crop improvement.}, } @article {pmid11130075, year = {2000}, author = {Grimson, MJ and Coates, JC and Reynolds, JP and Shipman, M and Blanton, RL and Harwood, AJ}, title = {Adherens junctions and beta-catenin-mediated cell signalling in a non-metazoan organism.}, journal = {Nature}, volume = {408}, number = {6813}, pages = {727-731}, doi = {10.1038/35047099}, pmid = {11130075}, issn = {0028-0836}, mesh = {Actins/metabolism ; Adherens Junctions/*metabolism/ultrastructure ; Amino Acid Sequence ; Animals ; Biological Evolution ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; Cell Differentiation/genetics ; Cytoskeletal Proteins/genetics/*metabolism ; Dictyostelium/cytology/*metabolism/ultrastructure ; Genes, Protozoan ; Glycogen Synthase Kinase 3 ; Molecular Sequence Data ; Mutagenesis ; Phosphorylation ; Recombinant Fusion Proteins/genetics/metabolism ; *Signal Transduction ; *Trans-Activators ; beta Catenin ; }, abstract = {Mechanical forces between cells have a principal role in the organization of animal tissues. Adherens junctions are an important component of these tissues, connecting cells through their actin cytoskeleton and allowing the assembly of tensile structures. At least one adherens junction protein, beta-catenin, also acts as a signalling molecule, directly regulating gene expression. To date, adherens junctions have only been detected in metazoa, and therefore we looked for them outside the animal kingdom to examine their evolutionary origins. The non-metazoan Dictyostelium discoideum forms a multicellular, differentiated structure. Here we describe the discovery of actin-associated intercellular junctions in Dictyostelium. We have isolated a gene encoding a beta-catenin homologue, aardvark, which is a component of the junctional complex, and, independently, is required for cell signalling. Our discovery of adherens junctions outside the animal kingdom shows that the dual role of beta-catenin in cell-cell adhesion and cell signalling evolved before the origins of metazoa.}, } @article {pmid11129428, year = {2000}, author = {Harrington, KJ and Syrigos, KN}, title = {The role of E-cadherin-catenin complex: more than an intercellular glue?.}, journal = {Annals of surgical oncology}, volume = {7}, number = {10}, pages = {783-788}, doi = {10.1007/s10434-000-0783-5}, pmid = {11129428}, issn = {1068-9265}, mesh = {Animals ; Cadherins/*physiology ; Carcinoma/*pathology ; Cell Adhesion/*physiology ; Cytoskeletal Proteins/*physiology ; Humans ; Neoplasm Invasiveness/*pathology ; Neoplasm Metastasis/*pathology ; Phenotype ; *Trans-Activators ; alpha Catenin ; beta Catenin ; }, abstract = {It is now widely recognized that alterations in the adhesion properties of neoplastic cells may play a pivotal role in the development and progression of the malignant phenotype in a range of tumor types. The cadherins and catenins, being the prime mediators of cell-cell adhesion, are intimately involved in the control of morphological differentiation and cellular proliferation; loss of their intercellular function allows malignant cells to escape from their site of origin, degrade the extracellular matrix, acquire a more motile and invasive phenotype, and, finally, invade and metastasize. In addition to participating in tumor invasiveness and metastasis, the E-cadherin-catenin complex is fundamental for the establishment and maintenance of multicellular organisms and regulates or significantly contributes to a variety of functions, including signal transduction, cell growth, differentiation, site-specific gene expression, morphogenesis, immunologic function, cell motility, wound healing, and inflammation. We reviewed the role of the E-cadherin-catenin complex in tumor development and presented the potential clinical applications of these molecules.}, } @article {pmid11128988, year = {2000}, author = {Oldham, S and Böhni, R and Stocker, H and Brogiolo, W and Hafen, E}, title = {Genetic control of size in Drosophila.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {355}, number = {1399}, pages = {945-952}, pmid = {11128988}, issn = {0962-8436}, mesh = {Animals ; Drosophila/*genetics/*growth & development ; Humans ; }, abstract = {During the past ten years, significant progress has been made in understanding the basic mechanisms of the development of multicellular organisms. Genetic analysis of the development of Caenorhabditis elegans and Drosophila has unearthed a fruitful number of genes involved in establishing the basic body plan, patterning of limbs, specification of cell fate and regulation of programmed cell death. The genes involved in these developmental processes have been conserved throughout evolution and homologous genes are involved in the patterning of insect and human limbs. Despite these important discoveries, we have learned astonishingly little about one of the most obvious distinctions between animals: their difference in body size. The mass of the smallest mammal, the bumble-bee bat, is 2 g while that of the largest mammal, the blue whale, is 150 t or 150 million grams. Remarkably, even though they are in the same class, body size can vary up to 75-million-fold. Furthermore, this body growth can be finite in the case of most vertebrates or it can occur continuously throughout life, as for trees, molluscs and large crustaceans. Currently, we know comparatively little about the genetic control of body size. In this article we will review recent evidence from vertebrates and particularly from Drosophila that implicates insulin/insulin-like growth factor-I and other growth pathways in the control of cell, organ and body size.}, } @article {pmid11127911, year = {2000}, author = {Queller, DC}, title = {Relatedness and the fraternal major transitions.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {355}, number = {1403}, pages = {1647-1655}, pmid = {11127911}, issn = {0962-8436}, mesh = {Animals ; *Selection, Genetic ; *Social Behavior ; }, abstract = {Many of the major transitions in evolution involved the coalescence of independent lower-level units into a higher organismal level. This paper examines the role of kinship, focusing on the transitions to multicellularity in animals and to coloniality in insects. In both, kin selection based on high relatedness permitted cooperation and a reproductive division of labour. The higher relatedness of haplodiploid females to their sisters than to their offspring might not have been crucial in the origin of insect societies, and the transition to multicellularity shows that such special relationships are not required. When multicellular forms develop from a single cell, selfish conflict is minimal because each selfish mutant obtains only one generation of within-individual advantage in a chimaera. Conditionally expressed traits are particularly immune to within-individual selfishness because such mutations are rarely expressed in chimaeras. Such conditionally expressed altruism genes lead easily to the evolution of the soma, and the germ line might simply be what is left over. In most social insects, differences in relatedness ensure that there will be potential conflicts. Power asymmetries sometimes lead to such decisive settlements of conflicts that social insect colonies can be considered to be fully organismal.}, } @article {pmid11125146, year = {2000}, author = {Wohlschlegel, JA and Dwyer, BT and Dhar, SK and Cvetic, C and Walter, JC and Dutta, A}, title = {Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.}, journal = {Science (New York, N.Y.)}, volume = {290}, number = {5500}, pages = {2309-2312}, doi = {10.1126/science.290.5500.2309}, pmid = {11125146}, issn = {0036-8075}, support = {CA60499/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Cell Cycle Proteins/chemistry/*metabolism/pharmacology ; Cell Nucleus/metabolism ; Cell-Free System ; Chromatin/metabolism ; *DNA Replication ; DNA-Binding Proteins/chemistry/*metabolism/pharmacology ; Evolution, Molecular ; G1 Phase ; G2 Phase ; Geminin ; HeLa Cells ; Humans ; *Interphase ; Molecular Sequence Data ; Molecular Weight ; Precipitin Tests ; Recombinant Fusion Proteins/metabolism ; Replication Origin ; *S Phase ; Xenopus ; Xenopus Proteins ; }, abstract = {In all eukaryotic organisms, inappropriate firing of replication origins during the G2 phase of the cell cycle is suppressed by cyclin-dependent kinases. Multicellular eukaryotes contain a second putative inhibitor of re-replication called geminin. Geminin is believed to block binding of the mini-chromosome maintenance (MCM) complex to origins of replication, but the mechanism of this inhibition is unclear. Here we show that geminin interacts tightly with Cdt1, a recently identified replication initiation factor necessary for MCM loading. The inhibition of DNA replication by geminin that is observed in cell-free DNA replication extracts is reversed by the addition of excess Cdt1. In the normal cell cycle, Cdt1 is present only in G1 and S, whereas geminin is present in S and G2 phases of the cell cycle. Together, these results suggest that geminin inhibits inappropriate origin firing by targeting Cdt1.}, } @article {pmid11124900, year = {2001}, author = {Vernis, L and Poljak, L and Chasles, M and Uchida, K and Casarégola, S and Käs, E and Matsuoka, M and Gaillardin, C and Fournier, P}, title = {Only centromeres can supply the partition system required for ARS function in the yeast Yarrowia lipolytica.}, journal = {Journal of molecular biology}, volume = {305}, number = {2}, pages = {203-217}, doi = {10.1006/jmbi.2000.4300}, pmid = {11124900}, issn = {0022-2836}, mesh = {Base Sequence ; Binding Sites ; Centromere/*genetics/metabolism ; Chromosome Breakage/genetics ; Chromosome Segregation/*genetics ; Chromosomes, Fungal/genetics/metabolism ; Cloning, Molecular ; Conserved Sequence/genetics ; DNA Replication ; DNA, Fungal/genetics/metabolism ; Molecular Sequence Data ; Mutagenesis, Insertional ; Nuclear Matrix/metabolism ; Plasmids/genetics/metabolism ; Regulatory Sequences, Nucleic Acid/genetics ; Replication Origin/*genetics ; Saccharomycetales/*genetics ; Sequence Deletion/genetics ; Transformation, Genetic ; }, abstract = {Autonomously replicating sequences (ARSs) in the yeast Yarrowia lipolytica require two components: an origin of replication (ORI) and centromere (CEN) DNA, both of which are necessary for extrachromosomal maintenance. To investigate this cooperation in more detail, we performed a screen for genomic sequences able to confer high frequency of transformation to a plasmid-borne ORI. Our results confirm a cooperation between ORI and CEN sequences to form an ARS, since all sequences identified in this screen displayed features of centromeric DNA and included the previously characterized CEN1-1, CEN3-1 and CEN5-1 fragments. Two new centromeric DNAs were identified as they are unique, map to different chromosomes (II and IV) and induce chromosome breakage after genomic integration. A third sequence, which is adjacent to, but distinct from the previously characterized CEN1-1 region was isolated from chromosome I. Although these CEN sequences do not share significant sequence similarities, they display a complex pattern of short repeats, including conserved blocks of 9 to 14 bp and regions of dyad symmetry. Consistent with their A+T-richness and strong negative roll angle, Y. lipolytica CEN-derived sequences, but not ORIs, were capable of binding isolated Drosophila nuclear scaffolds. However, a Drosophila scaffold attachment region that functions as an ARS in other yeasts was unable to confer autonomous replication to an ORI-containing plasmid. Deletion analysis of CEN1-1 showed that the sequences responsible for the induction of chromosome breakage could be eliminated without compromising extrachromosomal maintenance. We propose that, while Y. lipolytica CEN DNA is essential for plasmid maintenance, this function can be supplied by several sub-fragments which, together, form the active chromosomal centromere. This complex organization of Y. lipolytica centromeres is reminiscent of the regional structures described in the yeast Schizosaccharomyces pombe or in multicellular eukaryotes.}, } @article {pmid11116093, year = {2000}, author = {Nekrutenko, A and Li, WH}, title = {Assessment of compositional heterogeneity within and between eukaryotic genomes.}, journal = {Genome research}, volume = {10}, number = {12}, pages = {1986-1995}, pmid = {11116093}, issn = {1088-9051}, support = {R01 GM030998/GM/NIGMS NIH HHS/United States ; R37 GM030998/GM/NIGMS NIH HHS/United States ; GM30998/GM/NIGMS NIH HHS/United States ; GM55759/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; Base Composition ; Caenorhabditis elegans/genetics ; Centrifugation, Density Gradient ; Computational Biology ; Drosophila melanogaster/genetics ; Eukaryotic Cells/*physiology ; GC Rich Sequence/genetics ; *Genetic Heterogeneity ; *Genome ; Genome, Fungal ; Genome, Human ; Genome, Plant ; Humans ; Models, Genetic ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; }, abstract = {Using large amounts of long genomic sequences, we studied the compositional patterns of eukaryotic genomes. We developed a simple measure, the compositional heterogeneity (or variability) index, to compare the differences in compositional heterogeneity between long genomic sequences. The index measures the average difference in GC content between two adjacent windows normalized by the standard error expected under the assumption of random distribution of nucleotides in a window. We report the following findings: (1) The extent of the compositional heterogeneity in a genomic sequence strongly correlates with its GC content in all multicellular eukaryotes studied regardless of genome size. (2) The human genome appears to be highly compositionally heterogeneous both within and between individual chromosomes; the heterogeneity goes much beyond the predictions of the isochore model. (3) All genomes of multicellular eukaryotes examined in this study are compositionally heterogeneous, although they also contain compositionally uniform segments, or isochores. (4) The true uniqueness of the human (or mammalian) genome is the presence of very high GC regions, which exhibit unusually high compositional heterogeneity and contain few long homogeneous segments (isochores). In general, GC-poor isochores tend to be longer than GC-rich ones. These findings indicate that the genomes of multicellular organisms are much more heterogeneous in nucleotide composition than depicted by the isochore model and so lead to a looser definition of isochores.}, } @article {pmid11032307, year = {2000}, author = {Miguélez, EM and Hardisson, C and Manzanal, MB}, title = {Streptomycetes: a new model to study cell death.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {3}, number = {3}, pages = {153-158}, pmid = {11032307}, issn = {1139-6709}, mesh = {Biological Evolution ; *Cell Death ; Cell Division ; Energy Metabolism ; Eukaryotic Cells/cytology ; *Models, Biological ; Species Specificity ; Spores, Bacterial ; Streptomyces/*cytology/growth & development/physiology ; }, abstract = {Colonies of streptomycetes are now viewed as multicellular entities containing morphologically and biochemically differentiated cell types which have specific functions and precise spatial relationships to one another. Like multicellular organisms, colony development in streptomycetes is also maintained by a tight balance between cell proliferation and cell death processes. This review describes the current state of knowledge concerning cell death in streptomycetes.}, } @article {pmid11087177, year = {2000}, author = {Inouye, S and Jain, R and Ueki, T and Nariya, H and Xu, CY and Hsu, MY and Fernandez-Luque, BA and Munoz-Dorado, J and Farez-Vidal, E and Inouye, M}, title = {A large family of eukaryotic-like protein Ser/Thr kinases of Myxococcus xanthus, a developmental bacterium.}, journal = {Microbial & comparative genomics}, volume = {5}, number = {2}, pages = {103-120}, doi = {10.1089/10906590050179783}, pmid = {11087177}, issn = {1090-6592}, support = {GM-26843/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Chromosomes, Bacterial/genetics ; Cloning, Molecular ; Conserved Sequence ; Eukaryotic Cells/enzymology ; *Evolution, Molecular ; Gene Order/genetics ; Genes, Bacterial/genetics ; Histidine Kinase ; Isoenzymes/chemistry/genetics/metabolism ; Molecular Sequence Data ; Myxococcus xanthus/*enzymology/genetics ; Phylogeny ; Protein Kinases/metabolism ; Protein Serine-Threonine Kinases/*chemistry/genetics/metabolism ; Protein Structure, Tertiary ; Sequence Alignment ; }, abstract = {Myxococcus xanthus is a gram-negative bacterium that forms multicellular fruiting bodies upon starvation. Here, we demonstrate that it contains at least 13 eukaryotic-like protein Ser/Thr kinases (Pkn1 to Pkn13) individually having unique features. All contain the kinase domain of approximately 280 residues near the N-terminal end, which share highly conserved features in eukaryotic Ser/Thr kinases. The kinase domain is followed by a putative regulatory domain consisting of 185 to 692 residues. These regulatory domains share no significant sequence similarities. The C-terminal regions of 11 kinases contain at least 1 transmembrane domain, suggesting that they function as transmembrane sensor kinases. From the recent genomic analysis, protein Ser/Thr kinases were found in various pathogenic bacteria and coexist with protein His kinases. Phylogenetic analysis of these Ser/Thr kinases reveals that all bacterial Ser/Thr kinases were evolved from a common ancestral kinase together with eukaryotic Tyr and Ser/Thr kinases. Coexistence of both Ser/Thr and His kinases in some organisms may be significant in terms of functional differences between the two kinases. We argue that both kinases are essential for some bacteria to adapt optimally to severe environmental changes.}, } @article {pmid11080367, year = {2000}, author = {Rosenquist, M and Sehnke, P and Ferl, RJ and Sommarin, M and Larsson, C}, title = {Evolution of the 14-3-3 protein family: does the large number of isoforms in multicellular organisms reflect functional specificity?.}, journal = {Journal of molecular evolution}, volume = {51}, number = {5}, pages = {446-458}, doi = {10.1007/s002390010107}, pmid = {11080367}, issn = {0022-2844}, mesh = {14-3-3 Proteins ; Amino Acid Sequence ; Animals ; Conserved Sequence ; Databases, Factual ; *Evolution, Molecular ; Humans ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Phylogeny ; Protein Isoforms/genetics ; Sequence Alignment ; Tyrosine 3-Monooxygenase/chemistry/*genetics ; }, abstract = {14-3-3 proteins constitute a family of eukaryotic proteins that are key regulators of a large number of processes ranging from mitosis to apoptosis. 14-3-3s function as dimers and bind to particular motifs in their target proteins. To date, 14-3-3s have been implicated in regulation or stabilization of more than 35 different proteins. This number is probably only a fraction of the number of proteins that 14-3-3s bind to, as reports of new target proteins have become more frequent. An examination of 14-3-3 entries in the public databases reveals 153 isoforms, including alleloforms, reported in 48 different species. The number of isoforms range from 2, in the unicellular organism Saccharomyces cerevisiae, to 12 in the multicellular organism Arabidopsis thaliana. A phylogenetic analysis reveals that there are four major evolutionary lineages: Viridiplantae (plants), Fungi, Alveolata, and Metazoa (animals). A close examination of the aligned amino acid sequences identifies conserved amino acid residues and regions of importance for monomer stabilization, dimer formation, target protein binding, and the nuclear export function. Given the fact that 53% of the protein is conserved, including all amino acid residues in the target binding groove of the 14-3-3 monomer, one might expect little to no isoform specificity for target protein binding. However, using surface plasmon resonance we show that there are large differences in affinity between nine 14-3-3 isoforms of A. thaliana and a target peptide representing a novel binding motif present in the C terminus of the plant plasma membrane H(+)ATPase. Thus, our data suggest that one reason for the large number of isoforms found in multicellular organisms is isoform-specific functions.}, } @article {pmid11076022, year = {2000}, author = {Lengeler, JW}, title = {Metabolic networks: a signal-oriented approach to cellular models.}, journal = {Biological chemistry}, volume = {381}, number = {9-10}, pages = {911-920}, doi = {10.1515/BC.2000.112}, pmid = {11076022}, issn = {1431-6730}, mesh = {Animals ; *Cell Physiological Phenomena ; Eukaryotic Cells/physiology ; Humans ; Models, Biological ; Prokaryotic Cells/physiology ; Signal Transduction/genetics/*physiology ; }, abstract = {Complete genomes, far advanced proteomes, and even 'metabolomes' are available for at least a few organisms, e.g., Escherichia coli. Systematic functional analyses of such complete data sets will produce a wealth of information and promise an understanding of the dynamics of complex biological networks and perhaps even of entire living organisms. Such complete and holistic descriptions of biological systems, however, will increasingly require a quantitative analysis and the help of mathematical models for simulating whole systems. In particular, new procedures are required that allow a meaningful reduction of the information derived from complex systems that will consequently be used in the modeling process. In this review the biological elements of such a modeling procedure will be described. In a first step, complex living systems must be structured into well-defined and clearly delimited functional units, the elements of which have a common physiological goal, belong to a single genetic unit, and respond to the signals of a signal transduction system that senses changes in physiological states of the organism. These functional units occur at each level of complexity and more complex units originate by grouping several lower level elements into a single, more complex unit. To each complexity level corresponds a global regulator that is epistatic over lower level regulators. After its structuring into modules (functional units), a biological system is converted in a second step into mathematical submodels that by progressive combination can also be assembled into more aggregated model structures. Such a simplification of a cell (an organism) reduces its complexity to a level amenable to present modeling capacities. The universal biochemistry, however, promises a set of rules valid for modeling biological systems, from unicellular microorganisms and cells, to multicellular organisms and to populations.}, } @article {pmid11053678, year = {2000}, author = {Franceschi, C and Valensin, S and Bonafè, M and Paolisso, G and Yashin, AI and Monti, D and De Benedictis, G}, title = {The network and the remodeling theories of aging: historical background and new perspectives.}, journal = {Experimental gerontology}, volume = {35}, number = {6-7}, pages = {879-896}, doi = {10.1016/s0531-5565(00)00172-8}, pmid = {11053678}, issn = {0531-5565}, mesh = {*Aging ; Animals ; Biological Evolution ; Heat-Shock Proteins/biosynthesis ; Humans ; Immune System/physiology ; Inflammation/physiopathology ; Mice ; Saccharomyces cerevisiae/physiology ; }, abstract = {Two general theories, i.e. "the network theory of aging" (1989) and "the remodeling theory of aging" (1995), as well as their implications, new developments, and perspectives are reviewed and discussed. Particular attention has been paid to illustrate: (i) how the network theory of aging fits with recent data on aging and longevity in unicellular organisms (yeast), multicellular organisms (worms), and mammals (mice and humans); (ii) the evolutionary and experimental basis of the remodeling theory of aging (immunological, genetic, and metabolic data in healthy centenarians, and studies on the evolution of the immune response, stress and inflammation) and its recent development (the concepts of "immunological space" and "inflamm-aging"); (iii) the profound relationship between these two theories and the data which suggest that aging and longevity are related, in a complex way, to the capability to cope with a variety of stressors.}, } @article {pmid11041508, year = {2000}, author = {Jansen, RP}, title = {Origin and persistence of the mitochondrial genome.}, journal = {Human reproduction (Oxford, England)}, volume = {15 Suppl 2}, number = {}, pages = {1-10}, doi = {10.1093/humrep/15.suppl_2.1}, pmid = {11041508}, issn = {0268-1161}, mesh = {Animals ; DNA, Mitochondrial/chemistry/*genetics/metabolism ; Evolution, Molecular ; Extrachromosomal Inheritance ; *Genome ; Humans ; Mitochondria/*genetics ; Mutation ; }, abstract = {The mitochondrial genome comprises a circular, histone-free 'chromosome' of 16.6 kb of DNA, present in one or more copies in every mitochondrion. This chromosome has been tightly conserved for more than half a billion years, coding in every multicellular animal so far investigated, both vertebrate and invertebrate: (i) the same 13 protein subunits required for oxidative phosphorylation; (ii) a component of each of the two mitochondrial ribosome subunits; and (iii) the 22 transport RNAs present within the mitochondrion. Exons on the circle are tightly packed, with no spacing introns. Mitochondrial DNA is histone-free, has limited repair ability, and has a relatively high mutation-fixation rate. Inheritance is cytoplasmic and maternal, with epidemiological evidence (namely the familial distribution of polymorphisms) indicating that recombination with mtDNA of paternal origin is exceedingly rare. Thus the maintenance and evolution of mtDNA (its remarkably successful symbiotic persistence with the nuclear genome) has been essentially asexual. The machinery for homologous recombination is present in mitochondria of at least some species, however, and it might be surprising if it did not occur between circles in some circumstances. By bringing together the fields of mitochondrial biochemistry, evolutionary genetics, reproductive physiology, and neuromuscular medicine in focusing on the inheritance of normal and abnormal human mtDNA, we can hope to better understand the forces behind this genome's inheritance and what might be required of ovarian function to satisfy its accurate persistence over millions of years. Clinically we can hope also for a better understanding of ooplasmic factors in human fertility and in the wide manifestations of mitochondrial genomic disease.}, } @article {pmid11040290, year = {2000}, author = {Glöckner, G and Rosenthal, A and Valentin, K}, title = {The structure and gene repertoire of an ancient red algal plastid genome.}, journal = {Journal of molecular evolution}, volume = {51}, number = {4}, pages = {382-390}, doi = {10.1007/s002390010101}, pmid = {11040290}, issn = {0022-2844}, mesh = {Adaptation, Physiological/genetics ; Alkyl and Aryl Transferases/genetics ; *Bacterial Proteins ; Chloroplasts/genetics ; *Gene Order ; Genome ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Plastids/*genetics ; Rhodophyta/*genetics ; Transaminases/genetics ; }, abstract = {Photosynthetic eukaryotes can, according to features of their chloroplasts, be divided into two major groups: the red and the green lineage of plastid evolution. To extend the knowledge about the evolution of the red lineage we have sequenced and analyzed the chloroplast genome (cp-genome) of Cyanidium caldarium RK1, a unicellular red alga (AF022186). The analysis revealed that this genome shows several unusual structural features, such as a hypothetical hairpin structure in a gene-free region and absence of large repeat units. We provide evidence that this structural organization of the cp-genome of C. caldarium may be that of the most ancient cp-genome so far described. We also compared the cp-genome of C. caldarium to the other known cp-genomes of the red lineage. The cp-genome of C. caldarium cannot be readily aligned with that of Porphyra purpurea, a multicellular red alga, or Guillardia theta due to a displacement of a region of the cp-genome. The phylogenetic tree reveals that the secondary endosymbiosis, through which G. theta evolved, took place after the separation of the ancestors of C. caldarium and P. purpurea. We found several genes unique to the cp-genome of C. caldarium. Five of them seem to be involved in the building of bacterial cell envelopes and may be responsible for the thermotolerance of the chloroplast of this alga. Two additional genes may play a role in stabilizing the photosynthetic machinery against salt stress and detoxification of the chloroplast. Thus, these genes may be unique to the cp-genome of C. caldarium and may be required for the endurance of the extreme living conditions of this alga.}, } @article {pmid11029072, year = {2000}, author = {Atkins, MS and McArthur, AG and Teske, AP}, title = {Ancyromonadida: a new phylogenetic lineage among the protozoa closely related to the common ancestor of metazoans, fungi, and choanoflagellates (Opisthokonta).}, journal = {Journal of molecular evolution}, volume = {51}, number = {3}, pages = {278-285}, doi = {10.1007/s002390010089}, pmid = {11029072}, issn = {0022-2844}, mesh = {Animals ; Base Sequence ; DNA Primers/genetics ; DNA, Fungal/genetics ; DNA, Protozoan/genetics ; DNA, Ribosomal/genetics ; Eukaryota/*classification/*genetics/ultrastructure ; Evolution, Molecular ; Fungi/classification/genetics ; Likelihood Functions ; Microscopy, Electron, Scanning ; Models, Genetic ; *Phylogeny ; }, abstract = {Molecular and morphological evidence points to the ancyromonad Ancyromonas as a plausible candidate for the closest relative to the common ancestor of metazoans, fungi, and choanoflagellates (the Opisthokonta). Using 18S rDNA sequences from most of the major eukaryotic lineages, maximum-likelihood, minimum-evolution, and maximum-parsimony analyses yielded congruent phylogenies supporting this hypothesis. Combined with ultrastructural similarities between Ancyromonas and opisthokonts, the evidence presented here suggests that Ancyromonas may form an independent lineage, the Ancyromonadida Cavalier-Smith 1997, closer in its relationship to the opisthokonts than is its nearest protist relatives, the Apusomonadida. However, the very low bootstrap support for deep nodes and hypothesis testing indicate that the resolving power of 18S rDNA sequences is limited for examining this aspect of eukaryotic phylogeny. Alternate branching positions for the Ancyromonas lineage cannot be robustly rejected, revealing the importance of ultrastructure when examining the origins of multicellularity. The future use of a multigene approach may additionally be needed to resolve this aspect of eukaryotic phylogeny.}, } @article {pmid11010992, year = {2000}, author = {Zagórska-Marek, B and Turza&nacute;ska, M}, title = {Clonal Analysis Provides Evidence for Transient Initial Cells in Shoot Apical Meristems of Seed Plants.}, journal = {Journal of plant growth regulation}, volume = {19}, number = {1}, pages = {55-64}, doi = {10.1007/s003440000007}, pmid = {11010992}, issn = {0721-7595}, abstract = {Drift of mutated sectors in sectorial or mericlinal plant chimeras has been interpreted as indirect evidence of initial impermanence at the apex. However, the same effect may result from mutation in noninitial cells positioned close to the vertex of the apical dome. Clonal analysis of the cell packets present in the superficial layer of spruce and magnolia apices provided the library of patterns suggesting that the position and the number of initial cells, and in some cases also the meristem axis inclination, may change over time. Multicellular clones originating from a single cell have been found in the geometric center of some apices, whereas in other apices the cellular center (where three or four clonal borders meet) did not correspond to the geome}, } @article {pmid11001056, year = {2000}, author = {Hobmayer, B and Rentzsch, F and Kuhn, K and Happel, CM and von Laue, CC and Snyder, P and Rothbächer, U and Holstein, TW}, title = {WNT signalling molecules act in axis formation in the diploblastic metazoan Hydra.}, journal = {Nature}, volume = {407}, number = {6801}, pages = {186-189}, doi = {10.1038/35025063}, pmid = {11001056}, issn = {0028-0836}, mesh = {Adaptor Proteins, Signal Transducing ; Animals ; Body Patterning/physiology ; Cytoskeletal Proteins/metabolism ; Dishevelled Proteins ; *Hydra/embryology/metabolism ; Molecular Sequence Data ; Organizers, Embryonic ; Phosphoproteins/genetics/metabolism ; Polymerase Chain Reaction ; Proteins/metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; *Signal Transduction ; *Trans-Activators ; Wnt Proteins ; *Zebrafish Proteins ; beta Catenin ; }, abstract = {Members of the Wnt/wingless family of secreted proteins act as short-range inducers and long-range organizers during axis formation, organogenesis and tumorigenesis in many developing tissues. Wnt signalling pathways are conserved in nematodes, insects and vertebrates. Despite its developmental significance, the evolutionary origin of Wnt signalling is unclear. Here we describe the molecular characterization of members of the Wnt signalling pathway--Wnt, Dishevelled, GSK3, beta-Catenin and Tcf/Lef--in Hydra, a member of the evolutionarily old metazoan phylum Cnidaria. Wnt and Tcf are expressed in the putative Hydra head organizer, the upper part of the hypostome. Wnt, beta-Catenin and Tcf are transcriptionally upregulated when head organizers are established early in bud formation and head regeneration. Wnt and Tcf expression domains also define head organizers created by de novo pattern formation in aggregates. Our results indicate that Wnt signalling may be involved in axis formation in Hydra and support the idea that it was central in the evolution of axial differentiation in early multicellular animals.}, } @article {pmid11000110, year = {2000}, author = {Grosberg, RK and Hart, MW}, title = {Mate selection and the evolution of highly polymorphic self/nonself recognition genes.}, journal = {Science (New York, N.Y.)}, volume = {289}, number = {5487}, pages = {2111-2114}, doi = {10.1126/science.289.5487.2111}, pmid = {11000110}, issn = {0036-8075}, mesh = {*Alleles ; Animals ; Biological Evolution ; Cnidaria/*genetics/physiology ; Crosses, Genetic ; Female ; Genes ; Genotype ; Major Histocompatibility Complex ; Male ; *Polymorphism, Genetic ; *Sexual Behavior, Animal ; Urochordata/*genetics/physiology ; }, abstract = {Multicellular organisms use the products of highly polymorphic genes to distinguish self from conspecific nonself cells or tissues. These allorecognition polymorphisms may regulate somatic interactions between hosts and pathogens or between competitors (to avoid various forms of parasitism), as well as reproductive interactions between mates or between gametes (to avoid inbreeding). In both cases, rare alleles may be advantageous, but it remains unclear which mechanism maintains the genetic polymorphism for specificity in self/nonself recognition. Contrary to earlier reports, we show that mate selection cannot be a strong force maintaining allorecognition polymorphism in two colonial marine invertebrates. Instead, the regulation of intraspecific competitive interactions appears to promote the evolution of polymorphisms in these species.}, } @article {pmid10996508, year = {2000}, author = {Kannan, K and Jain, SK}, title = {Oxidative stress and apoptosis.}, journal = {Pathophysiology : the official journal of the International Society for Pathophysiology}, volume = {7}, number = {3}, pages = {153-163}, doi = {10.1016/s0928-4680(00)00053-5}, pmid = {10996508}, issn = {0928-4680}, abstract = {Apoptosis or programmed cell death, is essential for the normal functioning and survival of most multi-cellular organisms. The morphological and biochemical characteristics of apoptosis, however, are highly conserved during the evolution. It is currently believed that apoptosis can be divided into at least three functionally distinct phases, i.e. induction, effector and execution phase. Recent studies have demonstrated that reactive oxygen species (ROS) and the resulting oxidative stress play a pivotal role in apoptosis. Antioxidants and thiol reductants, such as N-acetylcysteine, and overexpression of manganese superoxide (MnSOD) can block or delay apoptosis. Bcl-2, an endogenously produced protein, has been shown to prevent cells from dying of apoptosis apparently by an antioxidative mechanism. Taken together ROS, and the resulting cellular redox change, can be part of signal transduction pathway during apoptosis. It is now established that mitochondria play a prominent role in apoptosis. During mitochondrial dysfunction, several essential players of apoptosis, including pro-caspases, cytochrome C, apoptosis-inducing factor (AIF), and apoptotic protease-activating factor-1 (APAF-1) are released into the cytosol. The multimeric complex formation of cytochrome C, APAF-1 and caspase 9 activates downstream caspases leading to apoptotic cell death. All the three functional phases of apoptosis are under the influence of regulatory controls. Thus, increasing evidences provide support that oxidative stress and apoptosis are closely linked physiological phenomena and are implicated in pathophysiology of some of the chronic diseases including AIDS, autoimmunity, cancer, diabetes mellitus, Alzheimer's and Parkinson's and ischemia of heart and brain.}, } @article {pmid10991141, year = {2000}, author = {Furusawa, C and Kaneko, K}, title = {Origin of complexity in multicellular organisms.}, journal = {Physical review letters}, volume = {84}, number = {26 Pt 1}, pages = {6130-6133}, doi = {10.1103/PhysRevLett.84.6130}, pmid = {10991141}, issn = {0031-9007}, mesh = {Cell Communication ; Cell Differentiation ; Cell Division ; *Cell Physiological Phenomena ; *Models, Biological ; Nonlinear Dynamics ; Stem Cells/cytology ; }, abstract = {Through extensive studies of dynamical system modeling cellular growth and reproduction, we find evidence that complexity arises in multicellular organisms naturally through evolution. Without any elaborate control mechanism, these systems can exhibit complex pattern formation with spontaneous cell differentiation. Such systems employ a "cooperative" use of resources and maintain a larger growth speed than simple cell systems, which exist in a homogeneous state and behave "selfishly." The relevance of the diversity of chemicals and reaction dynamics to the growth of a multicellular organism is demonstrated. Chaotic biochemical dynamics are found to provide the multipotency of stem cells.}, } @article {pmid10990067, year = {2000}, author = {Meade-Tollin, LC and Van Noorden, CJ}, title = {Time lapse phase contrast video microscopy of directed migration of human microvascular endothelial cells on matrigel.}, journal = {Acta histochemica}, volume = {102}, number = {3}, pages = {299-307}, doi = {10.1078/S0065-1281(04)70037-9}, pmid = {10990067}, issn = {0065-1281}, mesh = {Basement Membrane/metabolism ; Biocompatible Materials/chemistry ; Cell Line ; Cell Movement ; Collagen/*chemistry ; Drug Combinations ; Endothelium, Vascular/*metabolism ; Humans ; Laminin/*chemistry ; Microcirculation/*metabolism ; Microscopy, Phase-Contrast/*methods ; Microscopy, Video/*methods ; Neovascularization, Physiologic ; Proteoglycans/*chemistry ; Time Factors ; }, abstract = {Migration of microvascular endothelial cells is an early and critical step in angiogenesis. Formation of branching and polygonal cellular aggregates by endothelial cells on matrigel has often been considered to be an in vitro model for angiogenesis, although formation of lumens has not always been confirmed. The dynamics of migration of living cells of a human dermal microvascular endothelial cell line (HMEC-1) on a reconstituted basement membrane matrix have been captured in real time using time lapse video microscopy. The cells exhibit periods of quiescence and directed rapid migration by formation of extensions towards a specific target cell. Cells repeatedly extend flexible protrusions from the cell body both within the plane of the matrix and out of the plane of the matrix into the incubation medium. Connections between protrusions and target cells are made frequently, but not all cells which start to form protrusions achieve connections with other cells. Some of these migrating cells which do not connect arrest before reaching the target, or arrest and retract to their origin. After formation of multicellular polygonal structures, the structures contract to form amorphous clusters of fused cells without visible effects on the underlying matrix. The study demonstrates that time lapse video microscopy is a simple but very useful approach to monitor the dynamics of movements which vary in speed and frequency during migration of living cells.}, } @article {pmid10984721, year = {2000}, author = {Blackstone, NW}, title = {Redox control and the evolution of multicellularity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {22}, number = {10}, pages = {947-953}, doi = {10.1002/1521-1878(200010)22:10<947::AID-BIES10>3.0.CO;2-W}, pmid = {10984721}, issn = {0265-9247}, mesh = {Animals ; *Biological Evolution ; *Cells ; Oxidation-Reduction ; }, abstract = {Redox chemistry, involving the transfer of electrons and hydrogen atoms, is central to energy conversion in respiration; in addition, control of gene expression by redox state commonly occurs in bacteria, allowing a rapid response to environmental changes, such as altered food supply. Colonial metazoans often encrust surfaces over which the food supply varies in time or space; hence, in these organisms redox control of the development of feeding structures and gastrovascular connections could be similarly adaptive, allowing colonies to adjust the timing of development and spacing of structures in response to a variable food supply and other environmental factors. Experimental perturbations of redox state in colonial hydroids support this notion of adaptive redox control, and redox signaling in metazoans may have evolved in this ecological context. At the same time, redox signaling has important consequences for the evolutionary transition from unicellular to multicellular organisms. Unlike protein or peptide signaling, redox signaling acting in concert with programmed cell death may automatically inflict a cost on those cells that "defect," that is, selfishly favor their own replication rate over that of the multicellular group. In this way, redox signaling may have allowed multicellular individuality to evolve and more easily be maintained.}, } @article {pmid10972122, year = {2000}, author = {Lachmann, M and Sell, G and Jablonka, E}, title = {On the advantages of information sharing.}, journal = {Proceedings. Biological sciences}, volume = {267}, number = {1450}, pages = {1287-1293}, pmid = {10972122}, issn = {0962-8452}, mesh = {Animal Communication ; Animals ; Bacterial Physiological Phenomena ; Biological Evolution ; Insecta/physiology ; *Models, Theoretical ; *Social Behavior ; }, abstract = {During the evolution of life, there have been several transitions in which individuals began to cooperate, forming higher levels of organization, and sometimes losing their independent reproductive identity For example, multicellularity and insect societies evolved independently multiple times. Several factors that confer evolutionary advantages on higher levels of organization have been proposed. In this paper we highlight one additional factor: the sharing of information between individuals. Information sharing is not subject to the intrinsic conservation laws that characterize the sharing of physical resources. A simple model will illustrate how information sharing can result in aggregates in which the individuals both receive more information about their environment and pay less for it. This may have played a role in the evolution of higher levels of organization.}, } @article {pmid10968939, year = {2000}, author = {Kerszberg, M}, title = {The survival of slow reproducers.}, journal = {Journal of theoretical biology}, volume = {206}, number = {1}, pages = {81-89}, doi = {10.1006/jtbi.2000.2101}, pmid = {10968939}, issn = {0022-5193}, mesh = {Animals ; *Biological Evolution ; *Computer Simulation ; Fertility ; *Models, Statistical ; Parthenogenesis ; Reproduction/*physiology ; Sex ; Time Factors ; }, abstract = {Multicellularity, and the attendant segregation of the germ line, entails the loss of reproductive capacity by the soma: in Volvox carteri, less than 1 cell in 100 contributes to the next generation. However, compensatory advantages are unlikely to be very large (Koufopanou & Bell, 1993. Proc. R. Soc. Lond. (B) 254,107-113). Somewhat similarly, sex implies the generation of males, hence a dramatic reproductive slowdown (Barton & Charlesworth, 1998. Science281, 1986-1990); yet, a compensating (two-fold) advantage of sex has not been found. Here, I try to evaluate the actual cost of maintaining slow reproductive cycles, namely cycles that necessitate the production of "dead end" units such as somatic cells or males. In a quantitative model for the competition of individuals with different, heritable reproductive rates, this cost turns out to be unexpectedly small, and may even sometimes become irrelevant. The bases for this are made fairly clear: thus, when all enjoy high fecundity (e.g. a long reproductive life) the handicap of a slower reproduction vanishes; alternatively, a slight separation of ecological niches may be sufficient for survival of slower but otherwise unchanged reproducers; and finally, inherent to slow reproduction is a low rate of destabilizing genetic change. These facts are largely independent of the formal model details, and are supported by direct computer simulations. They give a quantitative basis for analysing the evolution and prevalence of slow life cycles. The implications of these findings for the evolution of multicellularity are briefly discussed.}, } @article {pmid10961916, year = {2000}, author = {Reddi, AH}, title = {Morphogenetic messages are in the extracellular matrix: biotechnology from bench to bedside.}, journal = {Biochemical Society transactions}, volume = {28}, number = {4}, pages = {345-349}, pmid = {10961916}, issn = {0300-5127}, mesh = {Animals ; *Bone Development ; Bone Morphogenetic Protein 4 ; Bone Morphogenetic Proteins/genetics/metabolism/physiology ; Bone and Bones/*physiology ; Carrier Proteins ; Cartilage/metabolism ; Cattle ; Chemotaxis ; Collagen/metabolism ; Extracellular Matrix/metabolism/*physiology ; Glycoproteins/metabolism ; Humans ; *Intercellular Signaling Peptides and Proteins ; Mice ; Protein Binding ; Proteins/metabolism ; Recombinant Proteins/metabolism ; }, abstract = {The origin and evolution of multicellular metazoa was accompanied by the appearance of extracellular matrix. The demineralized extracellular matrix of bone is enriched in morphogenetic proteins that induce bone. Bone morphogenetic proteins (BMPs) are intimately bound to collagens. BMP-4 has high affinity for type-IV collagen, and other binding proteins such as noggin and chordin. Soluble morphogens are kept in the solid state by extracellular matrix. In this sense Nature used the principles of affinity matrices long before humans patented the principle of affinity chromatography.}, } @article {pmid10959492, year = {2000}, author = {Sirén, AL and Knerlich, F and Schilling, L and Kamrowski-Kruck, H and Hahn, A and Ehrenreich, H}, title = {Differential glial and vascular expression of endothelins and their receptors in rat brain after neurotrauma.}, journal = {Neurochemical research}, volume = {25}, number = {7}, pages = {957-969}, pmid = {10959492}, issn = {0364-3190}, mesh = {Animals ; Base Sequence ; Brain/*metabolism ; Brain Injuries/*metabolism ; DNA Primers ; Endothelin-1/genetics/*metabolism ; Immunohistochemistry ; Male ; RNA, Messenger/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Endothelin/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {We characterized the time-course, intensity of expression and cellular origin of components of the endothelin (ET) system in the rat brain after a standardized neurotrauma (cryogenic lesion of the parietal cortex). ET mRNAs were expressed at sham level after neurotrauma, whereas immunoreactivity for ET-1 was enhanced in glia and endothelium of the lesioned hemisphere and both hippocampi. The number of ET-3 positive mononuclear cells in the lesion perimeter increased starting at 24h after injury. At 48h after neurotrauma, ET-receptor immunoreactivity was increased in astrocytes. In basilar artery endothelium, ETB-immunoreactivity was reduced at 48h to 72h recovering at 7 days whereas ETA-receptor and ET-peptide immunoreactivities were not altered. In summary, neurotrauma leads to a multicellular stimulation of endothelins in the brain along with a delayed selective loss of vascular ETB-receptors. These changes seem to be posttranscriptional and cell type specific. They favor vasoconstriction increasing the risk of late vasospasm and ischemia.}, } @article {pmid10952891, year = {2000}, author = {Walker, JD and Oppenheimer, DG and Concienne, J and Larkin, JC}, title = {SIAMESE, a gene controlling the endoreduplication cell cycle in Arabidopsis thaliana trichomes.}, journal = {Development (Cambridge, England)}, volume = {127}, number = {18}, pages = {3931-3940}, doi = {10.1242/dev.127.18.3931}, pmid = {10952891}, issn = {0950-1991}, support = {GM-5-30753/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/*cytology/*genetics/growth & development/ultrastructure ; Cell Cycle/*genetics ; Cell Differentiation/genetics ; Cell Lineage ; Cell Nucleus/genetics/ultrastructure ; Clone Cells ; DNA Replication/*genetics ; Darkness ; Genes, Plant/*genetics ; Histocytochemistry ; Hypocotyl/cytology/genetics/growth & development/ultrastructure ; Light ; Microscopy, Electron, Scanning ; Mitosis/genetics ; Morphogenesis/genetics ; Mutation ; Phenotype ; Plant Leaves/cytology/genetics/growth & development/ultrastructure ; }, abstract = {Cell differentiation is generally tightly coordinated with the cell cycle, typically resulting in a nondividing cell with a unique differentiated morphology. The unicellular trichomes of Arabidopsis are a well-established model for the study of plant cell differentiation. Here, we describe a new genetic locus, SIAMESE (SIM), required for coordinating cell division and cell differentiation during the development of Arabidopsis trichomes (epidermal hairs). A recessive mutation in the sim locus on chromosome 5 results in clusters of adjacent trichomes that appeared to be morphologically identical 'twins'. Upon closer inspection, the sim mutant was found to produce multicellular trichomes in contrast to the unicellular trichomes produced by wild-type (WT) plants. Mutant trichomes consisting of up to 15 cells have been observed. Scanning electron microscopy of developing sim trichomes suggests that the cell divisions occur very early in the development of mutant trichomes. WT trichome nuclei continue to replicate their DNA after mitosis and cytokinesis have ceased, and as a consequence have a DNA content much greater than 2C. This phenomenon is known as endoreduplication. Individual nuclei of sim trichomes have a reduced level of endoreduplication relative to WT trichome nuclei. Endoreduplication is also reduced in dark-grown sim hypocotyls relative to WT, but not in light-grown hypocotyls. Double mutants of sim with either of two other mutants affecting endoreduplication, triptychon (try) and glabra3 (gl3) are consistent with a function for SIM in endoreduplication. SIM may function as a repressor of mitosis in the endoreduplication cell cycle. Additionally, the relatively normal morphology of multicellular sim trichomes indicates that trichome morphogenesis can occur relatively normally even when the trichome precursor cell continues to divide. The sim mutant phenotype also has implications for the evolution of multicellular trichomes.}, } @article {pmid10931494, year = {2000}, author = {Blackstone, NW and Ellison, AM}, title = {Maximal indirect development, set-aside cells, and levels of selection.}, journal = {The Journal of experimental zoology}, volume = {288}, number = {2}, pages = {99-104}, doi = {10.1002/1097-010x(20000815)288:2<99::aid-jez2>3.0.co;2-r}, pmid = {10931494}, issn = {0022-104X}, mesh = {Animals ; *Biological Evolution ; Developmental Biology ; Models, Biological ; *Selection, Genetic ; }, abstract = {The evolution of metazoan development as described by Davidson et al. (1995. Science 270:1319-1325) is readily interpretable in terms of levels-of-selection conflicts, for instance, as recently modeled by Michod (1999. Darwinian Dynamics, Princeton, NJ: Princeton University Press). Davidson et al. propose certain features of early bilaterians including small size, a small and fixed number of cell divisions during and subsequent to cleavage, and specification of cell fates prior to cell movement. These features suggest constraints on certain parameters of Michod's model, specifically t (the time available for cell division) and b (the benefit to cells of not cooperating in terms of their rate of replication). Such constraints clearly enhance between-cell cooperation and allow multicellularity to more easily evolve and be maintained. Nevertheless, these constraints are completely abrogated by the phenomenon of "set-aside cells," that is, undifferentiated cells that retain indefinite division potential. Levels-of-selection theory predicts that the evolution of these set-aside cells must be accompanied by features which alleviate cell-cell competition, and indeed the results of Ransick et al. (1996. Proc Natl Acad Sci USA 93:6759-6763) support this prediction: the evolution of "set-aside cells" in metazoans was accompanied by the evolution of the sequestration of the germ line.}, } @article {pmid10928121, year = {2000}, author = {Bodey, B and Bodey, B and Siegel, SE and Kaiser, HE}, title = {The role of the reticulo-epithelial (RE) cell network in the immuno-neuroendocrine regulation of intrathymic lymphopoiesis.}, journal = {Anticancer research}, volume = {20}, number = {3A}, pages = {1871-1888}, pmid = {10928121}, issn = {0250-7005}, mesh = {Adolescent ; Adult ; Animals ; Antineoplastic Agents/pharmacology ; Child ; Child, Preschool ; Cytokines/immunology ; Epithelial Cells/drug effects/immunology/metabolism ; Fetus/cytology/ultrastructure ; Humans ; Hypothalamo-Hypophyseal System/immunology ; Immunohistochemistry ; Infant ; Infant, Newborn ; Leukopoiesis/drug effects ; Mice ; Mice, Inbred BALB C ; Neuropeptides/immunology ; Neurosecretory Systems/*cytology/immunology ; T-Lymphocyte Subsets/cytology/*immunology ; T-Lymphocytes/cytology/*immunology ; Thymus Gland/cytology/drug effects/*immunology/metabolism/ultrastructure ; Thymus Hormones/immunology ; Tretinoin/pharmacology ; }, abstract = {The thyrnus provides an optimal cellular and humoral microenvironment for the development of immunocompetent T lymphocytes. Although yolk sac derived pre-T, committed hematopoietic stem cells enter the thymus using a homing receptor, the immigration process also requires secretion of a peptide, called thymotaxin by the cells of the reticulo-epithelial (RE) network of the thymic cellular microenvironment. The thymic RE cells are functionally specialized based on their location within the thymic microenvironment. Thus, although subcapsular, cortical, and medullary RE cells are derived from a common, endodermal in origin epithelial precursor cell, their unique location within the gland causes their specialization in terms of their immunophenotypical and in situ physiological properties. The subcapsular, endocrine, RE cell layer (giant or nurse cells) is comprised of cells filled with PAS positive granules, which also express A2B5/TE4 cell surface antigens and MHC Class I (HLA A, B, C) molecules. In contrast to the medullary RE cells, these subcapsular nurse cells also produce thymosins beta 3 and beta 4. The thymic nurse cells (TNCs) display a neuroendocrine cell specific immunophenotype (IP): Thy-1+, A2B5+, TT+, TE4+, UJ13/A+, UJ127.11+, UJ167.11+, UJ181.4+, and presence of common leukocyte antigen (CLA+). Medullar RE cells display MHC Class II (HLA-DP, HLA-DQ, HLA- DR) molecule restriction. These cells also contain transforming growth factor (TGF)-beta type II receptors and are involved in the positive selection of T cells. Transmission electronmicroscopic (TEM) observations have defined four, functional subtypes of medullary RE cells: undifferentiated squamous, villous and cystic. All subtypes were connected with desmosomes. The secreted thy nic hormones, thymulin, thymosin-alpha 1 and thymopoietin (its short form, thymopentin or TP5) were detected immunocytochemically to be produced by RE cells. Thymic RE cells also produce numerous cytokines including IL-1, IL-6, G-CSF, M-CSF, and GM-CSF molecules that likely are important in various stages of thymocyte activation and differentiation. The co-existence of pituitary hormone and neuropeptide secretion [growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), triiodothyronine (T3), somatostatin, oxytocin (OT), follicle stimulating hormone (FSH), luteinizing hormone (LH), arginine vasopressin (AVP), growth hormone releasing hormone (GHRH), corticotropin releasing hormone (CRH), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), pro-enkephalin (pro-enk), and beta-endorphin (beta-end)], as well as production of a number of interleukins and growth factors and expression of receptors for all, by RE cells is an unique molecular biological phenomenon. The thymic RE cell network is most probably comprised of cells organized into sub-networks--functional units composed of RE cells with differing hormone production/hormone receptor expression profiles, involved in the various stages of T lymphocyte maturation. Furthermore, it is quite possible that even on the level of individual RE cells, the numerous projections associated with a single cell, which engulf developing lymphocytes, nurturing and guiding them in their maturation, may differ in their hormone production and/or hormone receptor expression profile, thus allowing a single cell to be involved in distinct, separate steps of the T cell maturation process. Based on our systematic observations of the thymus in humans and other mammalian species, we suggest that the thymic RE cells represent an extremely important cellular and humoral network within the thymic microenvironment and are involved in the homeopathic regulation mechanisms of the multicellular organism, in addition to the presentation of various antigens to developing lymphocytes, and providing growth regulatory signals which may range from stimulatory to apoptotic signaling within the thymus. (ABSTRACT TRUNCA}, } @article {pmid10905608, year = {2000}, author = {Graham, LK and Wilcox, LW}, title = {The origin of alternation of generations in land plants: a focus on matrotrophy and hexose transport.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {355}, number = {1398}, pages = {757-66; discussion 766-7}, pmid = {10905608}, issn = {0962-8436}, mesh = {Animals ; *Biological Evolution ; Biological Transport ; Hexoses/*metabolism ; Monosaccharide Transport Proteins/genetics/metabolism ; Plant Proteins/genetics/metabolism ; Plants/genetics/*metabolism ; }, abstract = {A life history involving alternation of two developmentally associated, multicellular generations (sporophyte and gametophyte) is an autapomorphy of embryophytes (bryophytesphytes + vascular plants). Microfossil data indicate that Mid Late Ordovician land plants possessed such a life cycle, and that the origin of alternation of generations preceded this date. Molecular phylogenetic data unambiguously relate charophycean green algae to the ancestry of monophyletic embryophytes, and identify bryophytes as early-divergent land plants. Comparison of reproduction in charophyceans and bryophytes suggests that the following stages occurred during evolutionary origin of embryophytic alternation of generations: (i) origin of oogamy; (ii) retention of eggs and zygotes on the parental thallus; (iii) origin of matrotrophy (regulated transfer of nutritional and morphogenetic solutes from parental cells to the next generation); (iv) origin of a multicellular sporophyte generation; and (v) origin of non-flagellate, walled spores. Oogamy, egg/zygote retention and matrotrophy characterize at least some modern charophvceans, and are postulated to represent pre-adaptative features inherited by embryophytes from ancestral charophyceans. Matrotrophy is hypothesized to have preceded origin of the multicellular sporophytes of' plants, and to represent a critical innovation. Molecular approaches to the study of the origins of matrotrophy include assessment of hexose transporter genes and protein family members and their expression patterns. The occurrence in modern charophyceans and bryophytes of chemically resistant tissues that exhibit distinctive morphology correlated with matrotrophy suggests that Early-Mid Ordovician or older microfossils relevant to the origin of land plant alternation of generations may be found.}, } @article {pmid10904874, year = {2000}, author = {Bodey, B and Bodey, B and Siegel, SE and Kaiser, HE}, title = {Novel insights into the function of the thymic Hassall's bodies.}, journal = {In vivo (Athens, Greece)}, volume = {14}, number = {3}, pages = {407-418}, pmid = {10904874}, issn = {0258-851X}, mesh = {Animals ; Dogs ; Female ; Homeodomain Proteins/metabolism ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Receptors, Transforming Growth Factor beta/metabolism ; Thymus Gland/metabolism/pathology/*physiology/ultrastructure ; Transcription Factors/metabolism ; *Xenopus Proteins ; }, abstract = {During thymic ontogenesis, the HBs appear when lymphopoiesis is already established and the cortex, medulla and the cortico-medullary junction are capable of conducting the positive and negative selection of T lymphocytes undergoing progressive maturation. The HBs are structurally organized from RE cells, which usually undergo hypertrophy prior to their inclusion in the outer cell layer of the corpuscles. The cellular microenvironment of the thymic medulla is composed of networks of cell types, of a variety of origins, and all of them may participate in the construction of growing, progressive HBs. Histochemically, we detected a rich content of basic non-histone proteins, PAS positive substance (glycogen) and acid mucopolysaccharides within the bodies. Employing the histological stain of Pasini and immunocytochemical methods with monoclonal antidodies (MoABs) AE2 and AE3, high molecular weight (56.5 to 67 kD) basic keratins were defined in human HBs. Employing a panel of MoABs developed against thymic RE cell surface antigens, we observed immunoreactivity localized to the outer cell layer of the HBs with MoABs TE8, TE16 and TE19, while the centrally located cells reacted positively with TE15 and TE19. Immunoreactivity in human skin, employing the TE8, TE16 and TE19 MoABs was also observed in the epidermal granulosa cell layer, while TE15 reacted with cells of the stratum corneum. The presence of endocrine, peptide secreting RE cells within the HBs was defined with the use of MoAB A2B5, which binds to the GQ ganglioside. The hypertrophied, physiologically active RE cells of the peripheral cell layer of the HBs reacted positively with medium to strong intensity when stained with MoABs UJ127.11, J1153, A2B5, 215.D11, and 275.G7. We also observed the expression of transforming growth factor-beta type II receptors in HBs. The recently detected expression of the homobox gene products B3, B4, and C6, transcription factors involved in developmental processes related to hematopoiesis within HBs provides further evidence that HBs are important functional components of the RE network of the thymus which provide developing thymocytes with paracrine and juxtacrine signals to ensure their proper functional maturation during intrathymic lymphopoiesis. Our transmission electronmicroscopical (TEM) studies on HBs determined the existence of groups of RE cells connected to one another by desmosomes. We also observed long cytoplasmic processes originating from medullary RE cells and directly contacting thymic T lymphocytes and accessory antigen presenting cells (macrophages, dendritic cells, interdigitating cells, Langerhans cells, etc.) by the use of scanning electronmicroscopy (SEM). Thus, our results indicate that the HBs are unique, antigenically distinct, functionally active, multicellular components of the nonlymphocytic, cellular micro-environment of the thymic medulla, and participate in the physiological activities of the prenatal and adult thymus.}, } @article {pmid10893943, year = {2000}, author = {Hughes-Jones, N}, title = {Inter-group aggression: the multi-individual organism and the survival instinct.}, journal = {Medicine, conflict, and survival}, volume = {16}, number = {2}, pages = {231-235}, doi = {10.1080/13623690008409516}, pmid = {10893943}, issn = {1362-3699}, mesh = {*Aggression ; Humans ; *Instinct ; *Survivors ; }, abstract = {Inter-group aggression, carried out at the level of the in-groups and out-groups of ethnocentric theory, continued unabated throughout the twentieth century. Its frequency, together with its ferocity, indicates a potent biological cause. We have evolved as social animals, and it is postulated that evolution has proceeded to such an extent that 'multi-individual social organisms', that is, 'social groups that fight each other are self-sustaining, self-replicating whole containing interdependent parts'. This results from the total integration of individuals into the social structure and culture of the in-group; individuals are inseparable from their society and evidence for this proposal is given. Cohesion is given through the collective consciousness and collective memory. The analogy is to multicellular organisms that evolved from the association of single cell organisms. All biological organisms are subject to the survival instinct, which is thus the potent biological cause of inter-group aggression. Groups compete for territory and see other groups as a threat. Prevention of inter-group aggression should come from the insight that threatening behaviour endangers the integrity of the society of out-groups, initiating conflict.}, } @article {pmid10879630, year = {2000}, author = {Böhm, M and Schröder, HC and Müller, IM and Müller, WE and Gamulin, V}, title = {The mitogen-activated protein kinase p38 pathway is conserved in metazoans: cloning and activation of p38 of the SAPK2 subfamily from the sponge Suberites domuncula.}, journal = {Biology of the cell}, volume = {92}, number = {2}, pages = {95-104}, doi = {10.1016/s0248-4900(00)89017-6}, pmid = {10879630}, issn = {0248-4900}, mesh = {Amino Acid Sequence ; Animals ; *Conserved Sequence ; Enzyme Activation ; Gene Library ; Genes, Immediate-Early ; Hot Temperature ; Hydrogen Peroxide/pharmacology ; Marine Biology ; Mitogen-Activated Protein Kinases/classification/*genetics ; Models, Genetic ; Molecular Sequence Data ; Osmotic Pressure ; Phylogeny ; Porifera/classification/drug effects/*genetics/radiation effects ; Sequence Analysis ; Sequence Homology, Amino Acid ; Signal Transduction ; Ultraviolet Rays ; p38 Mitogen-Activated Protein Kinases ; }, abstract = {Our recent data suggest that during auto- and allograft recognition in sponges (Porifera), cytokines are differentially expressed. Since the mitogen-activated protein kinase (MAPK) signal transduction modulates the synthesis and release of cytokines, we intended to identify one key molecule of this pathway. Therefore, a cDNA from the marine sponge Suberites domuncula encoding the MAPK was isolated and analyzed. Its encoded protein is 366 amino acids long (calculated Mr 42 209), has a TGY dual phosphorylation motif in protein kinase subdomain VIII and displays highest overall similarity to the mammalian p38 stress activated protein kinase (SAPK2), one subfamily of MAPKs. The sponge protein was therefore termed p38_SD. The overall homology (identity and similarity) between p38_SD and human p38alpha (CSBP2) kinase is 82%. One feature of the sponge kinase is the absence of threonine at position 106. In human p38alpha MAPK this residue is involved in the interaction with the specific pyridinyl-imidazole inhibitor; T106 is replaced in p38_SD by methionine. Inhibition studies with the respective inhibitor SB 203580 showed that it had no effect on the phosphorylation of the p38 substrate myelin basic protein. A stress responsive kinase Krs_SD similar to mammalian Ste20 kinases, upstream regulators of p38, had already previously been found in S. domuncula. The S. domuncula p38 MAPK is phosphorylated after treatment of the animal in hypertonic medium. In contrast, exposure of cells to hydrogen peroxide, heat shock and ultraviolet light does not cause any phosphorylation of p38. It is concluded that sponges, the oldest and most simple multicellular animals, utilize the conserved p38 MAPK signaling pathway, known to be involved in stress and immune (inflammatory) responses in higher animals.}, } @article {pmid10874755, year = {2000}, author = {Bromham, LD and Hendy, MD}, title = {Can fast early rates reconcile molecular dates with the Cambrian explosion?.}, journal = {Proceedings. Biological sciences}, volume = {267}, number = {1447}, pages = {1041-1047}, pmid = {10874755}, issn = {0962-8452}, mesh = {Animals ; *Biological Evolution ; Fossils ; Models, Biological ; }, abstract = {Molecular dates consistently place the divergence of major metazoan lineages in the Precambrian, leading to the suggestion that the 'Cambrian explosion' is an artefact of preservation which left earlier forms unrecorded in the fossil record. While criticisms of molecular analyses for failing to deal with variation in the rate of molecular evolution adequately have been countered by analyses which allow both site-to-site and lineage-specific rate variation, no analysis to date has allowed the rates to vary temporally. If the rates of molecular evolution were much higher early in the metazoan radiation, molecular dates could consistently overestimate the divergence times of lineages. Here, we use a new method which uses multiple calibration dates and an empirically determined range of possible substitution rates to place bounds on the basal date of divergence of lineages in order to ask whether faster rates of molecular evolution early in the metazoan radiation could possibly account for the discrepancy between molecular and palaeontological date estimates. We find that allowing basal (interphylum) lineages the fastest observed substitution rate brings the minimum possible divergence date (586 million years ago) to the Vendian period, just before the first multicellular animal fossils, but excludes divergence of the major metazoan lineages in a Cambrian explosion.}, } @article {pmid10867736, year = {2000}, author = {Hayward, DA}, title = {Better use of Darwinian concepts might change the way we look at some diseases.}, journal = {Medical hypotheses}, volume = {54}, number = {6}, pages = {895-899}, doi = {10.1054/mehy.1999.0972}, pmid = {10867736}, issn = {0306-9877}, mesh = {*Biological Evolution ; Genetic Diseases, Inborn/*genetics ; Humans ; Neoplasms/genetics/pathology ; }, abstract = {Medical science seems generally to be fixed in a paradigm within which individual organisms are viewed as harmonious units with all their component parts functioning towards a common good. This paper shows how a more revealing research methodology might be generated if a cellular, as opposed to organismic, perspective were used when thinking about some pathologies. From the cellular perspective, cells in multicellular organisms are seen to abandon intracellular cooperation and 'go solo' in some situations. This change in cellular conduct is facilitated by vestigial or introduced genetic instruction. When cells in multicellular organisms stop cooperating we call it disease.}, } @article {pmid10867638, year = {2000}, author = {Bogan, JA and Natale, DA and Depamphilis, ML}, title = {Initiation of eukaryotic DNA replication: conservative or liberal?.}, journal = {Journal of cellular physiology}, volume = {184}, number = {2}, pages = {139-150}, doi = {10.1002/1097-4652(200008)184:2<139::AID-JCP1>3.0.CO;2-8}, pmid = {10867638}, issn = {0021-9541}, mesh = {Animals ; DNA Replication/*physiology ; DNA-Binding Proteins/*physiology ; Eukaryotic Cells/*physiology ; Origin Recognition Complex ; Replication Origin/*physiology ; }, abstract = {The mechanism for initiation of eukaryotic DNA replication is highly conserved: the proteins required to initiate replication, the sequence of events leading to initiation, and the regulation of initiation are remarkably similar throughout the eukaryotic kingdom. Nevertheless, there is a liberal attitude when it comes to selecting initiation sites. Differences appear to exist in the composition of replication origins and in the way proteins recognize these origins. In fact, some multicellular eukaryotes (the metazoans) can change the number and locations of initiation sites during animal development, revealing that selection of initiation sites depends on epigenetic as well as genetic parameters. Here we have attempted to summarize our understanding of this process, to identify the similarities and differences between single cell and multicellular eukaryotes, and to examine the extent to which origin recognition proteins and replication origins have been conserved among eukaryotes. Published 2000 Wiley-Liss, Inc.}, } @article {pmid10863365, year = {2000}, author = {Dovgal', IV}, title = {[The morphological and ontogenetic changes in the Protozoa during the transition to a sessile mode of life].}, journal = {Zhurnal obshchei biologii}, volume = {61}, number = {3}, pages = {290-304}, pmid = {10863365}, issn = {0044-4596}, mesh = {*Adaptation, Physiological ; Animals ; Biological Evolution ; Eukaryota/*cytology/growth & development ; }, abstract = {The morphological adaptations of protozoans to sessile mode life and evolutionary changes in ontogeny are considered. There are main morphotypes of sessile protists: stalked organisms that attached to substrate by the extended base of body (basal disk), and unstalked organisms that are flatted on substrate. The origin of the morphotypes was independent in different taxa and involved nonhomologous structures. Adaptation to the sessile mode of life in the protists was connected with the progressive increase in the body size and intensity of organelle functions by polymerisation, subsequent division of function and change of functions. Evolution of adhesive organelles is characterised by growing intensity of their functions by allometric growth (usually without polymerisation), and in some cases with the subsequent division of functions and change of functions. The evolution manifests itself primarily in the organelles that provide interaction of cell with environment. The organelles that ensuring functioning of cell change due to correlations with the organelles of the first group. These two groups of organelles are similar to A.N. Sewertsoff's ecto- and endosomatic organs in multicellular organisms. The ontogeny of the sessile protists included three stages: formation of the migratory stage, distribution and choice of substrate and metamorphosis of the migratory stage after adhesion. As a rule there are no recapitulations on the first stage. The majority of structures tomotes or zoospores are inherited from the parent cell. Thus the present of some ancestral characteristics at the earlier stages of protistean ontogeny is display of the Baer's law. The main features of ontogeny evolution in sessile protists are the anaboly of the additional stages of life cycle, the displays of archallaxis or deviation during the migratory stage formation, and anaboly at the stage of buds morphogenesis after adhesion. At the last stage, the study of recapitulations is most perspective with the decision of phylogenetic problems in sessile protists.}, } @article {pmid10863076, year = {2000}, author = {Rube, CE and Uthe, D and Schmid, KW and Richter, KD and Wessel, J and Schuck, A and Willich, N and Rube, C}, title = {Dose-dependent induction of transforming growth factor beta (TGF-beta) in the lung tissue of fibrosis-prone mice after thoracic irradiation.}, journal = {International journal of radiation oncology, biology, physics}, volume = {47}, number = {4}, pages = {1033-1042}, doi = {10.1016/s0360-3016(00)00482-x}, pmid = {10863076}, issn = {0360-3016}, mesh = {Animals ; Dose-Response Relationship, Radiation ; Female ; Gene Expression/radiation effects ; Lung/metabolism/pathology/*radiation effects ; Mice ; Mice, Inbred C57BL ; Polymerase Chain Reaction ; Pulmonary Fibrosis/etiology/*metabolism/pathology ; RNA, Messenger/metabolism ; Radiation Pneumonitis/etiology/*metabolism/pathology ; Radiobiology ; Time Factors ; Transforming Growth Factor beta/metabolism/*radiation effects ; }, abstract = {PURPOSE: The lung is the major dose-limiting organ for radiotherapy of cancer in the thoracic region. The pathogenesis of radiation-induced lung injury at the molecular level is still unclear. Immediate cellular damage after irradiation is supposed to result in cytokine-mediated multicellular interactions with induction and progression of fibrotic tissue reactions. The purpose of this investigation was to evaluate the acute and long-term effects of radiation on the gene expression of transforming growth factor beta (TGF-beta) in a model of lung injury using fibrosis-sensitive C57BL/6 mice.

METHODS AND MATERIALS: The thoraces of C57BL/6 mice were irradiated with 6 and 12 Gy, respectively. Treated and sham-irradiated control mice were sacrificed at times corresponding to the latent period (1, 3, 6, 12, 24, 48, 72 hours and 1 week postirradiation), the pneumonic phase (2, 4, 8, and 16 weeks postirradiation), and the beginning of the fibrotic phase (24 weeks postirradiation). The lung tissue from three different mice per dosage and time point was analyzed by a combination of polymerase chain reaction (PCR), immunohistochemistry, and light microscopy. The mRNA expression of TGF-beta was quantified by competitive reverse transcriptase/polymerase chain reaction (RT-PCR); the cellular origin of the TGF-beta protein was identified by immunohistochemical staining (alkaline phosphatase-anti-alkaline phosphatase [APAAP]). The cytokine expression on mRNA and protein level was correlated with the histopathological alterations.

RESULTS: Following thoracic irradiation with a single dose of 12 Gy, radiation-induced TGF-beta release in lung tissue was appreciable already within the first hours (1, 3, and 6 hours postirradiation) and reached a significant increase after 12 hours; subsequently (48 hours, 72 hours, and 1 week postirradiation) the TGF-beta expression declined to basal levels. At the beginning of the pneumonic phase, irradiation-mediated stimulation of TGF-beta release reached maximal values at 2 and 4 weeks. The elevated levels of TGF-beta mRNA during the latent phase have been found to correlate with immunohistochemical staining of alveolar macrophages. The most striking increase in TGF-beta immunoreactivity was seen during the acute phase of pneumonitis. Throughout this observation period, type II pneumocytes and fibroblasts (apart from inflammatory cells) served as important sources of TGF-beta expression. Increased TGF-beta expression was detected prominently in regions of histopathologic radiation injury. After exposure to a single radiation dose of 6 Gy, the lung tissue revealed only a minor radiation-mediated TGF-beta mRNA response. The modest upregulation ranged from 6 hours to 48 hours after irradiation. Corresponding to the only minor histopathologic changes after thoracic irradiation with 6 Gy, measurement of TGF-beta mRNA levels during the later time points revealed no significant alterations in comparison to untreated control mice.

CONCLUSIONS: This study demonstrates an acute and long-lasting increase in the expression of TGF-beta in lung tissue following thoracic irradiation with 12 Gy. The predominant localization of TGF-beta in areas of inflammatory cell infiltrates and fibrosis suggests involvement of this cytokine in the pathogenesis of radiation-induced pulmonal fibrosis. Further studies should be performed to explore the role of other cytokines in the development of radiation injury. An improved understanding of the underlying mechanisms of pulmonary fibrosis may eventually lead to modulatory intervention at the molecular level to modify the fibrotic process.}, } @article {pmid10842308, year = {2000}, author = {Thacker, C and Rose, AM}, title = {A look at the Caenorhabditis elegans Kex2/Subtilisin-like proprotein convertase family.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {22}, number = {6}, pages = {545-553}, doi = {10.1002/(SICI)1521-1878(200006)22:6<545::AID-BIES7>3.0.CO;2-F}, pmid = {10842308}, issn = {0265-9247}, mesh = {Animals ; Caenorhabditis elegans/*enzymology/genetics ; Genes, Helminth ; Humans ; Multigene Family ; Mutation ; Phylogeny ; *Proprotein Convertases ; *Saccharomyces cerevisiae Proteins ; Subtilisins/chemistry/genetics/*metabolism ; }, abstract = {Significant advances have recently been made in our understanding of the mechanisms of activation of proteins that require processing. Often this involves endoproteolytic cleavage of precursor forms at basic residues, and is carried out by a group of serine endoproteinases, termed the proprotein convertases. In mammals, seven different convertases have been identified to date. These act in both the regulated secretory pathway for the processing of prohormones and proneuropeptides and in the constitutive secretory pathway, in which a variety of proproteins are activated endoproteolytically. The recently completed sequence of the nematode Caenorhabditis elegans genome affords a unique opportunity to examine the entire proprotein convertase family in a multicellular organism. Here we review the nature of the family, emphasising the structural features, characteristic of the four nematode genes, that supply all of the necessary functions unique to this group of serine endoproteinases. Studies of the C. elegans genes not only provide important information about the evaluation of this gene family but should help to illuminate the roles of these proteins in mammalian systems. BioEssays 22:545-553, 2000.}, } @article {pmid10839531, year = {2000}, author = {Hyde, WT and Crowley, TJ and Baum, SK and Peltier, WR}, title = {Neoproterozoic 'snowball Earth' simulations with a coupled climate/ice-sheet model.}, journal = {Nature}, volume = {405}, number = {6785}, pages = {425-429}, doi = {10.1038/35013005}, pmid = {10839531}, issn = {0028-0836}, mesh = {Animals ; *Biological Evolution ; Climate ; Earth, Planet ; Ice ; Models, Biological ; *Snow ; }, abstract = {Ice sheets may have reached the Equator in the late Proterozoic era (600-800 Myr ago), according to geological and palaeomagnetic studies, possibly resulting in a 'snowball Earth'. But this period was a critical time in the evolution of multicellular animals, posing the question of how early life survived under such environmental stress. Here we present computer simulations of this unusual climate stage with a coupled climate/ice-sheet model. To simulate a snowball Earth, we use only a reduction in the solar constant compared to present-day conditions and we keep atmospheric CO2 concentrations near present levels. We find rapid transitions into and out of full glaciation that are consistent with the geological evidence. When we combine these results with a general circulation model, some of the simulations result in an equatorial belt of open water that may have provided a refugium for multicellular animals.}, } @article {pmid10835644, year = {2000}, author = {Ewing, B and Green, P}, title = {Analysis of expressed sequence tags indicates 35,000 human genes.}, journal = {Nature genetics}, volume = {25}, number = {2}, pages = {232-234}, doi = {10.1038/76115}, pmid = {10835644}, issn = {1061-4036}, mesh = {Alternative Splicing/genetics ; Artifacts ; Chromosomes, Human, Pair 22/genetics ; Computational Biology ; Contig Mapping ; *Expressed Sequence Tags ; *Genes ; *Genome, Human ; Humans ; RNA, Messenger/analysis/genetics ; }, abstract = {The number of protein-coding genes in an organism provides a useful first measure of its molecular complexity. Single-celled prokaryotes and eukaryotes typically have a few thousand genes; for example, Escherichia coli has 4,300 and Saccharomyces cerevisiae has 6,000. Evolution of multicellularity appears to have been accompanied by a several-fold increase in gene number, the invertebrates Caenorhabditis elegans and Drosophila melanogaster having 19,000 and 13,600 genes, respectively. Here we estimate the number of human genes by comparing a set of human expressed sequence tag (EST) contigs with human chromosome 22 and with a non-redundant set of mRNA sequences. The two comparisons give mutually consistent estimates of approximately 35,000 genes, substantially lower than most previous estimates. Evolution of the increased physiological complexity of vertebrates may therefore have depended more on the combinatorial diversification of regulatory networks or alternative splicing than on a substantial increase in gene number.}, } @article {pmid10817970, year = {2000}, author = {Puigderrajols, P and Celestino, C and Suils, M and Toribio, M and Molinas, M}, title = {Histology of Organogenic and Embryogenic Responses in Cotyledons of Somatic Embryos of Quercus Suber L.}, journal = {International journal of plant sciences}, volume = {161}, number = {3}, pages = {353-362}, doi = {10.1086/314266}, pmid = {10817970}, issn = {1058-5893}, abstract = {In cork oak (Quercus suber L.), recurrent embryogenesis is produced in vitro through autoembryony without exogenous plant growth regulators (PGRs); secondary embryos appear on the embryo axis but seldom on cotyledons. Focusing mainly on the histological origin of neoformations, we investigated the influence of the embryo axis and exogenous PGRs on the embryogenic potential of somatic embryo cotyledons. Isolated cotyledons of somatic embryos became necrotic when cultured on PGR-free medium but gave secondary embryos when cultured on media containing benzyladenine and naphthaleneacetic acid. Cotyledons of cork oak somatic embryos are competent to give embryogenic responses. Isolated cotyledons without a petiole showed a lower percentage of embryogenic response than did those with a petiole. In petioles, somatic embryos arose from inner parenchyma tissues following a multicellular budding pattern. Joined to the embryo axis, cotyledons did not show morphogenic responses when cultured on PGR-free medium but revealed budlike and phylloid formations when cultured on medium with PGRs. The different morphogenic behavior displayed by somatic cotyledons indicates an influence of the embryo axis and indicates a relationship between organogenic and embryogenic regeneration pathways.}, } @article {pmid10810093, year = {2000}, author = {Lai, CH and Chou, CY and Ch'ang, LY and Liu, CS and Lin, W}, title = {Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics.}, journal = {Genome research}, volume = {10}, number = {5}, pages = {703-713}, pmid = {10810093}, issn = {1088-9051}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence/genetics ; Caenorhabditis elegans/*genetics ; Computational Biology ; Conserved Sequence/*genetics ; Databases, Factual ; *Evolution, Molecular ; Expressed Sequence Tags ; *Genes, Helminth ; Humans ; Molecular Sequence Data ; Organ Specificity/genetics ; Proteome/*genetics ; }, abstract = {Modern biomedical research greatly benefits from large-scale genome-sequencing projects ranging from studies of viruses, bacteria, and yeast to multicellular organisms, like Caenorhabditis elegans. Comparative genomic studies offer a vast array of prospects for identification and functional annotation of human ortholog genes. We presented a novel comparative proteomic approach for assembling human gene contigs and assisting gene discovery. The C. elegans proteome was used as an alignment template to assist in novel human gene identification from human EST nucleotide databases. Among the available 18,452 C. elegans protein sequences, our results indicate that at least 83% (15,344 sequences) of C. elegans proteome has human homologous genes, with 7,954 records of C. elegans proteins matching known human gene transcripts. Only 11% or less of C. elegans proteome contains nematode-specific genes. We found that the remaining 7,390 sequences might lead to discoveries of novel human genes, and over 150 putative full-length human gene transcripts were assembled upon further database analyses. [The sequence data described in this paper have been submitted to the}, } @article {pmid10808709, year = {2000}, author = {Sonin, MD and Beér, SA and Roĭtman, VA and Sergiev, VP and Romanenko, NA}, title = {[Regularity of formation of environmental parasitic contamination in urbanized ecosystems].}, journal = {Meditsinskaia parazitologiia i parazitarnye bolezni}, volume = {}, number = {1}, pages = {7-11}, pmid = {10808709}, issn = {0025-8326}, mesh = {Animals ; Biological Evolution ; Disease Vectors ; *Ecosystem ; *Environmental Pollution ; Host-Parasite Interactions ; Humans ; Parasites/*pathogenicity ; Parasitic Diseases/epidemiology/parasitology ; *Systems Theory ; *Urbanization ; }, abstract = {The materials are summarized on the basis of which the authors were given Diploma No. 118 (with priority from November 23, 1994, registered under No. 137) for discovery of the same name by the resolution of the International Association of Authors of Scientific Discoveries on May 12, 1999. FORMULA OF THE DISCOVERY: "The unknown hitherto regularity of formation of environmental parasitic contamination in urbanized ecosystems has been ascertained to embrace the following. In emergency of biosocial conditions leading to parameters: (structures, functions, regulatory mechanisms) transformations of evolutionary established parasitic systems owing to the development of expression, expansion and succession in protozoa and multicellular parasitic organisms' populations, the conditions arise that favour the violation of biocenoses homeostasis and changes in tension of epidemic, epizootic and epiphytotic processes during parasitoses". The discovery pertains to the field of biology in particular, to general, ecological, medical, veterinary and agricultural aspects of parasitology.}, } @article {pmid10800375, year = {2000}, author = {Brasier, MD}, title = {The Cambrian explosion and the slow burning fuse.}, journal = {Science progress}, volume = {83 (Pt 1)}, number = {}, pages = {77-92}, pmid = {10800375}, issn = {0036-8504}, abstract = {The rapid appearance of animal phyla in the fossil record during the 'Cambrian explosion' ca 543 Myr ago marks the most conspicuous turning point in earth history. This 'explosion' was preceded by a 'slow burning fuse', from the start of the prokaryote fossil record at ca 3450 Myr BP to endosymbiotic assembly of the eukaryote cell between ca 2,700 and 1,000 Myr. Research is beginning to put these events into their environmental context. Very long periods of environmental stability are suggested by the carbon isotopic and palaeoclimatic record prior to ca 1,000 Myr. Such stasis may have nurtured endosymbioses to the point at which eukaryotic organization and sexual reproduction became embedded in the genome. This steady state world was chaotically disrupted in the prelude to the Cambrian explosion. Strontium, sulphur and carbon isotopes attained maximal values during this time, and the latter show chaotic oscillations coincident with flips between extreme, low latitude glaciations and possible supergreenhouse conditions. These chaotic bifurcations may have been caused by tectonically driven increases in nutrient flux to the oceans and/or by the impact of multicellularity on the carbon cycle. Whatever the cause, high rates of biotic turnover during these times of stress could have radically redirected and/or accelarated the path of evolution towards new animal body plans.}, } @article {pmid10798200, year = {2000}, author = {Vincent, WF and Gibson, JA and Pienitz, R and Villeneuve, V and Broady, PA and Hamilton, PB and Howard-Williams, C}, title = {Ice shelf microbial ecosystems in the high arctic and implications for life on snowball earth.}, journal = {Die Naturwissenschaften}, volume = {87}, number = {3}, pages = {137-141}, doi = {10.1007/s001140050692}, pmid = {10798200}, issn = {0028-1042}, mesh = {Animals ; Arctic Regions ; Canada ; Ciliophora/isolation & purification ; Cyanobacteria/isolation & purification ; *Ecosystem ; Eukaryota/isolation & purification ; *Ice ; Nematoda/isolation & purification ; Rotifera/isolation & purification ; Viruses/isolation & purification ; Water/*parasitology ; *Water Microbiology ; }, abstract = {The Ward Hunt Ice Shelf (83 degrees N, 74 degrees W) is the largest remaining section of thick (> 10 m) land-fast sea ice along the northern coastline of Ellesmere Island, Canada. Extensive meltwater lakes and streams occur on the surface of the ice and are colonized by photosynthetic microbial mat communities. This High Arctic cryo-ecosystem is similar in several of its physical, biological and geochemical features to the McMurdo Ice Shelf in Antarctica. The ice-mats in both polar regions are dominated by filamentous cyanobacteria but also contain diatoms, chlorophytes, flagellates, ciliates, nematodes, tardigrades and rotifers. The luxuriant Ward Hunt consortia also contain high concentrations (10(7)-10(8) cm-2) of viruses and heterotrophic bacteria. During periods of extensive ice cover, such as glaciations during the Proterozoic, cryotolerant mats of the type now found in these polar ice shelf ecosystems would have provided refugia for the survival, growth and evolution of a variety of organisms, including multicellular eukaryotes.}, } @article {pmid10760743, year = {2000}, author = {Czaker, R}, title = {Extracellular matrix (ECM) components in a very primitive multicellular animal, the dicyemid mesozoan Kantharella antarctica.}, journal = {The Anatomical record}, volume = {259}, number = {1}, pages = {52-59}, doi = {10.1002/(SICI)1097-0185(20000501)259:1<52::AID-AR6>3.0.CO;2-J}, pmid = {10760743}, issn = {0003-276X}, mesh = {Animals ; Antarctic Regions ; Collagen/metabolism ; Extracellular Matrix/*metabolism/ultrastructure ; Fibronectins/metabolism ; Invertebrates/*metabolism/*ultrastructure ; Laminin/metabolism ; Phylogeny ; }, abstract = {One of the most vital synapomorphic properties of metazoans is the presence of an extracellular matrix (ECM), i.e., a complex of proteoglycans, adhesive glycoproteins, and collagens. The genetically controlled ECM mediates between the respective receptors morphogenesis and cell differentiation and is central to gastrulation, i.e., the process which generates the embryonic germ layers, upon which all metazoan body structures are based. However, the primitive metazoans include a phylum, viz. the Dicyemida, which lacks any kind of typical metazoan ECM structures including a basement membrane, and hence does not develop through gastrulation. Since the ECM components fibronectin, laminin, and type IV collagen, all of which are essential constituents of each basement membrane, have been proved to be evolutionary ancient molecules from the lowest metazoans up to vertebrates, antibodies against the respective vertebrate ECM components were employed by electron microscopy to look for these molecules also in the dicyemid mesozoan Kantharella antarctica. As a result, all three protein families showed an immunolabel which was localized intracellularly and intimately associated with the cell membranes as well as with the submembranously arranged delicate filamentous network. The immunolabel was most intense in the fibronectin-like protein, followed by the type IV collagen-like protein and weakest in the laminin-like protein. From an evolutionary point of view, this kind of distribution of ECM components, primarily found in intracellular regions, seems to reflect a very primitive situation of the structures of the respective ECM molecules having not yet reached their definitive position outside the cell, thus generating the complete biological function of typical ECM. Moreover, these results confirm the long-standing presumption that the dicyemid mesozoan body structure might be the missing link between the Protozoa and Metazoa.}, } @article {pmid10719670, year = {2000}, author = {Medzhitov, R and Janeway, C}, title = {Innate immune recognition: mechanisms and pathways.}, journal = {Immunological reviews}, volume = {173}, number = {}, pages = {89-97}, doi = {10.1034/j.1600-065x.2000.917309.x}, pmid = {10719670}, issn = {0105-2896}, support = {P01 AI44220-01/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Antigens/*immunology ; Biological Evolution ; Conserved Sequence ; *Immune System ; Immunity, Innate ; Molecular Sequence Data ; NF-kappa B/metabolism ; *Receptors, Immunologic ; Signal Transduction ; Transcriptional Activation ; }, abstract = {The innate immune system is an evolutionarily ancient form of host defense found in most multicellular organisms. Inducible responses of the innate immune system are triggered upon pathogen recognition by a set of pattern recognition receptors. These receptors recognize conserved molecular patterns shared by large groups of microorganisms. Recognition of these patterns allows the innate immune system not only to detect the presence of an infectious microbe, but also to determine the type of the infecting pathogen. Pattern recognition receptors activate conserved host defense signaling pathways that control the expression of a variety of immune response genes.}, } @article {pmid10700733, year = {2000}, author = {Maina, JN}, title = {Comparative respiratory morphology: themes and principles in the design and construction of the gas exchangers.}, journal = {The Anatomical record}, volume = {261}, number = {1}, pages = {25-44}, doi = {10.1002/(SICI)1097-0185(20000215)261:1<25::AID-AR6>3.0.CO;2-7}, pmid = {10700733}, issn = {0003-276X}, mesh = {Animals ; *Biological Evolution ; Gills/*physiology/*ultrastructure ; Humans ; In Vitro Techniques ; Lung/*physiology/*ultrastructure ; Pulmonary Gas Exchange/*physiology ; }, abstract = {Along the evolutionary continuum, a kaleidoscope of gas exchangers has evolved from the simple cell membrane of the primeval unicells. The most momentous events in this process were: the intensification of molecular oxygen in the biosphere and its appropriation into aerobic metabolism, the rise of multicellular organisms, the development of a circulatory system and carrier pigments in blood, the advocacy of air breathing, adoption of suctional breathing, and the shift to endothermy. To satisfy species-specific needs for oxygen, some constraints were overcome through transactions that obliged certain compromises and trade-offs. Optimal designs of the gas exchangers for particular phylogenetic levels of development, habitat, and lifestyle have developed only so far as to satisfy prescribed needs. The efficiency of the human lung, for example, falls well below those of certain taxa that are considered to be relatively "less advanced." Utilizing different resources and strategies, in fascinating processes of conformity, different groups of animals have developed similar respiratory structures. In most cases, the analogy reflects evolutionary convergence in response to corresponding selective pressures rather than common ancestry. Anat Rec (New Anat) 261:25-44, 2000.}, } @article {pmid10673278, year = {2000}, author = {McCue, LA and McDonough, KA and Lawrence, CE}, title = {Functional classification of cNMP-binding proteins and nucleotide cyclases with implications for novel regulatory pathways in Mycobacterium tuberculosis.}, journal = {Genome research}, volume = {10}, number = {2}, pages = {204-219}, doi = {10.1101/gr.10.2.204}, pmid = {10673278}, issn = {1088-9051}, support = {5RO1-HG0125703/HG/NHGRI NIH HHS/United States ; }, mesh = {Adenylyl Cyclases/metabolism ; Amino Acid Sequence ; Carrier Proteins/*classification/*metabolism ; Computational Biology ; Guanylate Cyclase/metabolism ; Molecular Sequence Data ; Mycobacterium tuberculosis/*enzymology/metabolism ; Nucleotides, Cyclic/*metabolism ; Phosphorus-Oxygen Lyases/*classification/*metabolism ; Phylogeny ; Sequence Alignment ; }, abstract = {We have analyzed the cyclic nucleotide (cNMP)-binding protein and nucleotide cyclase superfamilies using Bayesian computational methods of protein family identification and classification. In addition to the known cNMP-binding proteins (cNMP-dependent kinases, cNMP-gated channels, cAMP-guanine nucleotide exchange factors, and bacterial cAMP-dependent transcription factors), new functional groups of cNMP-binding proteins were identified, including putative ABC-transporter subunits, translocases, and esterases. Classification of the nucleotide cyclases revealed subtle differences in sequence conservation of the active site that distinguish the five classes of cyclases: the multicellular eukaryotic adenylyl cyclases, the eukaryotic receptor-type guanylyl cyclases, the eukaryotic soluble guanylyl cyclases, the unicellular eukaryotic and prokaryotic adenylyl cyclases, and the putative prokaryotic guanylyl cyclases. Phylogenetic distribution of the cNMP-binding proteins and cyclases was analyzed, with particular attention to the 22 complete archaeal and eubacterial genome sequences. Mycobacterium tuberculosis H37Rv and Synechocystis PCC6803 were each found to encode several more putative cNMP-binding proteins than other prokaryotes; many of these proteins are of unknown function. M. tuberculosis also encodes several more putative nucleotide cyclases than other prokaryotic species.}, } @article {pmid10642882, year = {2000}, author = {Kappen, C}, title = {The homeodomain: an ancient evolutionary motif in animals and plants.}, journal = {Computers & chemistry}, volume = {24}, number = {1}, pages = {95-103}, doi = {10.1016/s0097-8485(99)00049-2}, pmid = {10642882}, issn = {0097-8485}, mesh = {Amino Acids/genetics ; Animals ; *Evolution, Molecular ; Gene Expression Regulation ; Homeodomain Proteins/chemistry/*genetics ; Molecular Sequence Data ; Plant Proteins/*chemistry ; }, abstract = {The homeodomain is a DNA-binding motif within transcription factor proteins. These transcription factors may be involved in cell differentiation and control of cell growth, as well as patterning of diverse organisms. Given their strong evolutionary conservation, it has been suggested that homeodomain proteins have been fundamental to the evolution of animal species. We have previously shown that the major classes of animal homeodomains originated early in the evolution of metazoans. Here, I investigate the evolutionary relationships of homeodomain sequences in plants. Using distance matrix approaches with unweighted or weighted character state transitions, the overall results support the same conclusion: in plants, as in animals, multiple independent classes of divergent homeodomains can be distinguished, again suggesting an early evolutionary origin. These studies advance the hypothesis that the homeodomain represents a fundamental motif of gene regulation in multicellular organisms.}, } @article {pmid11125040, year = {2001}, author = {Tatusov, RL and Natale, DA and Garkavtsev, IV and Tatusova, TA and Shankavaram, UT and Rao, BS and Kiryutin, B and Galperin, MY and Fedorova, ND and Koonin, EV}, title = {The COG database: new developments in phylogenetic classification of proteins from complete genomes.}, journal = {Nucleic acids research}, volume = {29}, number = {1}, pages = {22-28}, pmid = {11125040}, issn = {1362-4962}, mesh = {Animals ; Archaea/genetics ; Bacteria/genetics ; Caenorhabditis elegans/genetics ; *Databases, Factual ; Drosophila melanogaster/genetics ; Genome ; Information Storage and Retrieval ; Internet ; Phylogeny ; *Proteins/classification/genetics ; Saccharomyces cerevisiae/genetics ; Sequence Alignment ; }, abstract = {The database of Clusters of Orthologous Groups of proteins (COGs), which represents an attempt on a phylogenetic classification of the proteins encoded in complete genomes, currently consists of 2791 COGs including 45 350 proteins from 30 genomes of bacteria, archaea and the yeast Saccharomyces cerevisiae (http://www.ncbi.nlm.nih. gov/COG). In addition, a supplement to the COGs is available, in which proteins encoded in the genomes of two multicellular eukaryotes, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, and shared with bacteria and/or archaea were included. The new features added to the COG database include information pages with structural and functional details on each COG and literature references, improvements of the COGNITOR program that is used to fit new proteins into the COGs, and classification of genomes and COGs constructed by using principal component analysis.}, } @article {pmid10629110, year = {1999}, author = {Whitfield, GK and Jurutka, PW and Haussler, CA and Haussler, MR}, title = {Steroid hormone receptors: evolution, ligands, and molecular basis of biologic function.}, journal = {Journal of cellular biochemistry}, volume = {Suppl 32-33}, number = {}, pages = {110-122}, doi = {10.1002/(sici)1097-4644(1999)75:32+<110::aid-jcb14>3.0.co;2-t}, pmid = {10629110}, issn = {0730-2312}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Cholesterol/biosynthesis ; Dimerization ; *Evolution, Molecular ; Humans ; Ligands ; Molecular Sequence Data ; Protein Structure, Tertiary ; Receptors, Cytoplasmic and Nuclear/chemistry/classification/metabolism ; Receptors, Steroid/chemistry/classification/*metabolism ; }, abstract = {The characterization of the superfamily of nuclear receptors, in particular the steroid/retinoid/thyroid hormone receptors, has resulted in a more complete understanding of how a repertoire of hormonally and nutritionally derived lipophilic ligands controls cell functions to effect development and homeostasis. As transducers of hormonal signaling in the nucleus, this superfamily of DNA-binding proteins appears to represent a crucial link in the emergence of multicellular organisms. Because nuclear receptors bind and are conformationally activated by a chemically diverse array of ligands, yet are closely related in general structure, they present an intriguing example of paralogous evolution. It is hypothesized that an ancient prototype receptor evolved into an intricate set of dimerizing isoforms, capable of recognizing an ensemble of hormone-responsive element motifs in DNA, and exerting ligand-directed combinatorial control of gene expression. The effector domains of nuclear receptors mediate transcriptional activation by recruiting coregulatory multisubunit complexes that remodel chromatin, target the initiation site, and stabilize the RNA polymerase II machinery for repeated rounds of transcription of the regulated gene. Because some nuclear receptors also function in gene repression, while others are constitutive activators, this superfamily of proteins provides a number of avenues for investigating hormonal regulation of gene expression. This review surveys briefly the latest findings in the nuclear receptor field and identifies particular areas where future studies should be fruitful. J. Cell. Biochem. Suppls. 32/33:110-122, 1999.}, } @article {pmid10629096, year = {2000}, author = {Dewel, RA}, title = {Colonial origin for Emetazoa: major morphological transitions and the origin of bilaterian complexity.}, journal = {Journal of morphology}, volume = {243}, number = {1}, pages = {35-74}, doi = {10.1002/(SICI)1097-4687(200001)243:1<35::AID-JMOR3>3.0.CO;2-#}, pmid = {10629096}, issn = {0362-2525}, mesh = {Animals ; Cnidaria/anatomy & histology/classification/genetics ; Evolution, Molecular ; *Invertebrates/anatomy & histology/classification/genetics ; Phylogeny ; Porifera/anatomy & histology/classification/genetics ; }, abstract = {A new hypothesis for the evolution of Bilateria is presented. It is based on a reinterpretation of the morphological characters shared by protostomes and deuterostomes, which, when taken together with developmental processes shared by the two lineages, lead to the inescapable conclusion that the last common ancestor of Bilateria was complex. It possessed a head, a segmented trunk, and a tail. The segmented trunk was further divided into two sections. A dorsal brain innervated one or more sensory cells, which included photoreceptors. "Appendages" or outgrowths were present. The bilaterian ancestor also possessed serially repeated "segments" that were expressed ontogenetically as blocks of mesoderm or somites with adjoining fields of ectoderm or neuroectoderm. It displayed serially repeated gonads (gonocoels), each with a gonoduct and gonopore to the exterior, and serially repeated "coeloms" with connections to both the gut and the exterior (gill slits and pores). Podocytes, some of which were serially repeated in the trunk, formed sites of ultrafiltration. In addition, the bilaterian ancestor had unsegmented coeloms and a contractile blood vessel or "heart" formed by coelomic myoepithelial cells. These cells and their underlying basement membrane confine the hemocoelic fluid, or blood, in the connective tissue compartment. A possible scenario to account for this particular suite of characters is one in which a colony of organisms with a cnidarian grade of organization became individuated into a new entity with a bilaterian grade of organization. The transformation postulated encompassed three major transitions in the evolution of animals. These transitions included the origins of Metazoa, Eumetazoa, and Bilateria and involved the successive development of poriferan, cnidarian, and bilaterian grades of organization. Two models are presented for the sponge-to-cnidarian transition. In both models the loss of a flow-through pattern of water circulation in poriferans and the establishment of a single opening and epithelia sensu stricto in cnidarians are considered crucial events. In the model offered for the cnidarian-to-bilaterian transition, the last common ancestor of Eumetazoa is considered to have had a colonial, cnidarian-grade of organization. The ancestral cnidarian body plan would have been similar to that exhibited by pennatulacean anthozoans. It is postulated that a colonial organization could have provided a preadaptive framework for the evolution of the complex and modularized body plan of the triploblastic ancestor of Bilateria. Thus, one can explore the possibility that problematica such as ctenophores, the Ediacaran biota, archaeocyaths, and Yunnanozoon reflect the fact that complexity originated early and involved the evolution of a macroscopic compartmented ancestor. Bilaterian complexity can be understood in terms of Beklemishev "cycles" of duplication and colony individuation. Two such cycles appear to have transpired in the early evolution of Metazoa. The first gave rise to a multicellular organism with a sponge grade of organization and the second to the modularized ancestor of Bilateria. The latter episode may have been favored by the ecological conditions in the late Proterozoic. Whatever its cause, the individuation of a cnidarian-grade colony furnishes a possible explanation for the rapid diversification of bilaterians in the late Vendian and Cambrian. The creation of a complex yet versatile prototype, which could be rapidly modified by selection into a profusion of body plans, is postulated to have affected the timing, mode, and extent of the "Cambrian explosion." During the radiations, selective loss or simplification may have been as creative a force as innovation. Finally, colony individuation may have been a unique historical event that imprinted the development of bilaterians as the zootype and phylotypic stage. (ABSTRACT TRUNCATED)}, } @article {pmid10617574, year = {1999}, author = {Schumacher, K and Vafeados, D and McCarthy, M and Sze, H and Wilkins, T and Chory, J}, title = {The Arabidopsis det3 mutant reveals a central role for the vacuolar H(+)-ATPase in plant growth and development.}, journal = {Genes & development}, volume = {13}, number = {24}, pages = {3259-3270}, pmid = {10617574}, issn = {0890-9369}, mesh = {Amino Acid Sequence ; Animals ; Arabidopsis/enzymology/*genetics/*growth & development ; Cloning, Molecular ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Plant ; Humans ; Light ; Molecular Sequence Data ; Phylogeny ; Proton Pumps/metabolism ; Proton-Translocating ATPases/chemistry/*genetics/*metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; *Vacuolar Proton-Translocating ATPases ; }, abstract = {In all multicellular organisms growth and morphogenesis must be coordinated, but for higher plants, this is of particular importance because the timing of organogenesis is not fixed but occurs in response to environmental constraints. One particularly dramatic developmental juncture is the response of dicotyledonous seedlings to light. The det3 mutant of Arabidopsis develops morphologically as a light-grown plant even when it is grown in the dark. In addition, it shows organ-specific defects in cell elongation and has a reduced response to brassinosteroids (BRs). We have isolated the DET3 gene by positional cloning and provide functional and biochemical evidence that it encodes subunit C of the vacuolar H(+)-ATPase (V-ATPase). We show that the hypocotyl elongation defect in the det3 mutant is conditional and provide evidence that this is due to an alternative mechanism of V-ATPase assembly. Together with the expression pattern of the DET3 gene revealed by GFP fluorescence, our data provide in vivo evidence for a role for the V-ATPase in the control of cell elongation and in the regulation of meristem activity.}, } @article {pmid10611686, year = {1999}, author = {Meyerowitz, EM}, title = {Plants, animals and the logic of development.}, journal = {Trends in cell biology}, volume = {9}, number = {12}, pages = {M65-8}, pmid = {10611686}, issn = {0962-8924}, mesh = {Animals ; Arabidopsis/genetics ; Caenorhabditis elegans/genetics ; Cell Communication ; Cell Membrane ; Cell Nucleus ; Cytoplasm ; *Evolution, Molecular ; Growth/*genetics/physiology ; Plants/genetics ; }, abstract = {Multicellular plants and animals have evolved independently from a unicellular, last common ancestor. Each lineage started with a common toolkit of functioning genes and evolved to complex, multicellular forms. Comparison of the genes used to serve similar functions shows how organisms can use different genes for similar ends and thereby reveals the principles of development.}, } @article {pmid10607653, year = {1999}, author = {Kirk, DL}, title = {Evolution of multicellularity in the volvocine algae.}, journal = {Current opinion in plant biology}, volume = {2}, number = {6}, pages = {496-501}, doi = {10.1016/s1369-5266(99)00019-9}, pmid = {10607653}, issn = {1369-5266}, mesh = {Animals ; Chlamydomonas/cytology/genetics ; Chlorophyta/*cytology/*genetics ; *Evolution, Molecular ; Phylogeny ; }, abstract = {Recent studies reveal that relationships among the volvocine algae are more complex than was previously believed. Nevertheless, this group still appears to provide an unrivaled opportunity to analyze an evolutionary pathway leading from unicellularity (Chlamydomonas) to multicellularity with division of labor (Volvox). Significant progress in this regard was made in the past year when two genes playing key roles in Volvox cellular differentiation were cloned, and clues were uncovered regarding their mechanisms of action.}, } @article {pmid10607613, year = {1999}, author = {Aravind, L and Subramanian, G}, title = {Origin of multicellular eukaryotes - insights from proteome comparisons.}, journal = {Current opinion in genetics & development}, volume = {9}, number = {6}, pages = {688-694}, doi = {10.1016/s0959-437x(99)00028-3}, pmid = {10607613}, issn = {0959-437X}, mesh = {Animals ; Arabidopsis/chemistry ; Caenorhabditis elegans/chemistry ; Cell Differentiation ; Eukaryotic Cells/*cytology/*metabolism ; *Evolution, Molecular ; *Phylogeny ; Proteins/chemistry/metabolism ; *Proteome ; Saccharomyces cerevisiae/chemistry ; }, abstract = {The complete genomes of the yeast Saccharomyces cerevisiae and the nematode worm Caenorhabditis elegans have recently become available allowing the comparison of the complete protein sets of a unicellular and multicellular eukaryote for the first time. These comparisons reveal some striking trends in terms of expansions or extensive shuffling of specific domains that are involved in regulatory functions and signaling. Similar comparisons with the available sequence data from the plant Arabidopsis thaliana produce consistent results. These observations have provided useful insights regarding the origin of multicellular organisms.}, } @article {pmid10603307, year = {1999}, author = {Omura, T}, title = {Forty years of cytochrome P450.}, journal = {Biochemical and biophysical research communications}, volume = {266}, number = {3}, pages = {690-698}, doi = {10.1006/bbrc.1999.1887}, pmid = {10603307}, issn = {0006-291X}, mesh = {Animals ; Catalysis ; Cell Transformation, Neoplastic ; Cytochrome P-450 Enzyme System/chemistry/*history/metabolism ; History, 20th Century ; Hormones/biosynthesis/history ; Lipid Metabolism ; Lipids/history ; Protein Conformation ; Xenobiotics/history/metabolism ; }, abstract = {The term "cytochrome P450" first appeared in literature in 1962. It was a microsomal membrane-bound hemoprotein without known physiological functions at that time and was characterized by a unique 450-nm optical absorption peak of its carbon monoxide-bound form, which was originally reported as the spectrum of a novel "microsomal carbon monoxide-binding pigment" in 1958. Elucidation of its function as the oxygenase in 1963 triggered a rapid expansion of research on this hemoprotein. Annual numbers of the published papers dealing with cytochrome P450, which were listed in Biological Abstracts, increased from 60 in 1970 to 500 in 1980, 900 in 1990, and 1500 in 1997. Cytochrome P450 is now regarded as the collective name of a large family of hemoproteins, "cytochrome P450 superfamily, "which seems to have diversified from a single ancestral protein to many forms during the course of biological evolution and is distributed widely among various forms of life from animals and plants to fungi and bacteria. Multicellular eukaryotic organisms including animals and plants have about 100 or more P450 genes in their genomes, and those many P450 genes are expressed tissue specifically and developmental stage specifically, indicating their diverse physiological functions. In mammals, various P450s participate in the biosynthesis and metabolism of sterols and steroid hormones and the metabolism of various lipid biofactors including eicosanoids, vitamin D3, and retinoids. Oxidative metabolism of foreign hydrophobic compounds as the first step of their excretion from the animal body is apparently another major function of cytochrome P450, which protects animals from noxious foreign compounds, man-created and natural.}, } @article {pmid10597636, year = {1999}, author = {Lundin, LG}, title = {Gene duplications in early metazoan evolution.}, journal = {Seminars in cell & developmental biology}, volume = {10}, number = {5}, pages = {523-530}, doi = {10.1006/scdb.1999.0333}, pmid = {10597636}, issn = {1084-9521}, mesh = {Animals ; Chordata, Nonvertebrate/genetics ; Collagen/genetics ; *Evolution, Molecular ; *Gene Duplication ; Genome ; Homeodomain Proteins/genetics ; Phylogeny ; Receptors, Cytoplasmic and Nuclear/genetics ; }, abstract = {Major increases in complexity during animal evolution occurred at the transition from a unicellular protozoan to a multicellular metazoan, the evolution of Bilateria from diploblasts (possibly the Cambrian explosion) and during early vertebrate evolution. A role for gene duplication in the third event has been widely discussed. Here I examine the possible role of gene duplications and domain shuffling in the first two events. There is evidence for a wave of gene duplications and shuffling which may have paved the way for multicellularity; there are also examples of gene duplications that may have facilitated the transition from diploblasts to Bilateria.}, } @article {pmid10585970, year = {1999}, author = {Macario, AJ and Lange, M and Ahring, BK and Conway de Macario, E}, title = {Stress genes and proteins in the archaea.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {63}, number = {4}, pages = {923-67, table of contents}, pmid = {10585970}, issn = {1092-2172}, mesh = {Adaptation, Biological/*genetics ; Amino Acid Sequence ; Archaea/classification/*physiology/ultrastructure ; Archaeal Proteins/chemistry/*genetics ; *Genes, Archaeal ; Heat-Shock Proteins/chemistry/classification/genetics ; Heat-Shock Response/*genetics ; Molecular Chaperones/chemistry/classification/genetics ; Molecular Sequence Data ; Phylogeny ; }, abstract = {The field covered in this review is new; the first sequence of a gene encoding the molecular chaperone Hsp70 and the first description of a chaperonin in the archaea were reported in 1991. These findings boosted research in other areas beyond the archaea that were directly relevant to bacteria and eukaryotes, for example, stress gene regulation, the structure-function relationship of the chaperonin complex, protein-based molecular phylogeny of organisms and eukaryotic-cell organelles, molecular biology and biochemistry of life in extreme environments, and stress tolerance at the cellular and molecular levels. In the last 8 years, archaeal stress genes and proteins belonging to the families Hsp70, Hsp60 (chaperonins), Hsp40(DnaJ), and small heat-shock proteins (sHsp) have been studied. The hsp70(dnaK), hsp40(dnaJ), and grpE genes (the chaperone machine) have been sequenced in seven, four, and two species, respectively, but their expression has been examined in detail only in the mesophilic methanogen Methanosarcina mazei S-6. The proteins possess markers typical of bacterial homologs but none of the signatures distinctive of eukaryotes. In contrast, gene expression and transcription initiation signals and factors are of the eucaryal type, which suggests a hybrid archaeal-bacterial complexion for the Hsp70 system. Another remarkable feature is that several archaeal species in different phylogenetic branches do not have the gene hsp70(dnaK), an evolutionary puzzle that raises the important question of what replaces the product of this gene, Hsp70(DnaK), in protein biogenesis and refolding and for stress resistance. Although archaea are prokaryotes like bacteria, their Hsp60 (chaperonin) family is of type (group) II, similar to that of the eukaryotic cytosol; however, unlike the latter, which has several different members, the archaeal chaperonin system usually includes only two (in some species one and in others possibly three) related subunits of approximately 60 kDa. These form, in various combinations depending on the species, a large structure or chaperonin complex sometimes called the thermosome. This multimolecular assembly is similar to the bacterial chaperonin complex GroEL/S, but it is made of only the large, double-ring oligomers each with eight (or nine) subunits instead of seven as in the bacterial complex. Like Hsp70(DnaK), the archaeal chaperonin subunits are remarkable for their evolution, but for a different reason. Ubiquitous among archaea, the chaperonins show a pattern of recurrent gene duplication-hetero-oligomeric chaperonin complexes appear to have evolved several times independently. The stress response and stress tolerance in the archaea involve chaperones, chaperonins, other heat shock (stress) proteins including sHsp, thermoprotectants, the proteasome, as yet incompletely understood thermoresistant features of many molecules, and formation of multicellular structures. The latter structures include single- and mixed-species (bacterial-archaeal) types. Many questions remain unanswered, and the field offers extraordinary opportunities owing to the diversity, genetic makeup, and phylogenetic position of archaea and the variety of ecosystems they inhabit. Specific aspects that deserve investigation are elucidation of the mechanism of action of the chaperonin complex at different temperatures, identification of the partners and substitutes for the Hsp70 chaperone machine, analysis of protein folding and refolding in hyperthermophiles, and determination of the molecular mechanisms involved in stress gene regulation in archaeal species that thrive under widely different conditions (temperature, pH, osmolarity, and barometric pressure). These studies are now possible with uni- and multicellular archaeal models and are relevant to various areas of basic and applied research, including exploration and conquest of ecosystems inhospitable to humans and many mammals and plants.}, } @article {pmid10356356, year = {1999}, author = {Lu, Y and Settleman, J}, title = {The role of rho family GTPases in development: lessons from Drosophila melanogaster.}, journal = {Molecular cell biology research communications : MCBRC}, volume = {1}, number = {2}, pages = {87-94}, doi = {10.1006/mcbr.1999.0119}, pmid = {10356356}, issn = {1522-4724}, mesh = {Animals ; Drosophila melanogaster/embryology/*genetics ; Gastrula ; Morphogenesis ; Oogenesis ; Signal Transduction ; rho GTP-Binding Proteins/*genetics/metabolism/physiology ; }, abstract = {It has become increasingly clear in the last few years that the Rho family GTPases regulate cytoskeleton rearrangements that are essential for a variety of morphogenetic events associated with the development of multicellular organisms. In particular, Drosophila has provided an excellent in vivo system for deciphering the signaling pathways mediated by Rho GTPases, as well as establishing the role of these pathways in numerous developmental processes. Continued use of this system will undoubtedly lead to the identification of additional Rho signalling components and information regarding the function and organization of the Rho signaling pathways in tissue morphogenesis. The striking similarity between Drosophila and mammalian Rho signaling components identified thus far indicates that the Rho pathways are highly conserved in evolution. Therefore, the findings from the Drosophila system can be extrapolated to higher organisms, including humans. Combined with the rapid progress in the human and Drosophila genome projects, these findings should contribute greatly to our understanding of mammalian Rho GTPase signaling pathways and their roles in normal development and pathological conditions.}, } @article {pmid10574579, year = {1999}, author = {Hernandez, CJ and Hazelwood, SJ and Martin, RB}, title = {The relationship between basic multicellular unit activation and origination in cancellous bone.}, journal = {Bone}, volume = {25}, number = {5}, pages = {585-587}, doi = {10.1016/s8756-3282(99)00201-x}, pmid = {10574579}, issn = {8756-3282}, support = {AR41644/AR/NIAMS NIH HHS/United States ; }, mesh = {Bone Development/physiology ; Bone Remodeling/*physiology ; Bone Resorption/physiopathology ; Bone and Bones/cytology/*physiology ; Humans ; Osteoblasts/physiology ; Osteoclasts/physiology ; }, abstract = {Activation frequency is often used as a measure of basic multicellular unit (BMU) activity in cancellous bone. However, activation frequency expresses the rate of BMU appearance in a histologic slide and not the rate of origination, which is a more physiologic indicator of remodeling activity and is necessary for the development of BMU-level bone remodeling simulations. Using identical assumptions to those for calculating the activation frequency, it is shown that the origination frequency in cancellous bone is equal to the activation frequency divided by the total distance traveled by the BMU and its width.}, } @article {pmid10571011, year = {1999}, author = {Schachter, H and Jaeken, J}, title = {Carbohydrate-deficient glycoprotein syndrome type II.}, journal = {Biochimica et biophysica acta}, volume = {1455}, number = {2-3}, pages = {179-192}, doi = {10.1016/s0925-4439(99)00054-x}, pmid = {10571011}, issn = {0006-3002}, mesh = {Animals ; Carbohydrate Sequence ; Congenital Disorders of Glycosylation/blood/diagnosis/*genetics ; Disease Models, Animal ; Evolution, Molecular ; Glycoproteins/biosynthesis/blood ; Glycosylation ; *Hexosyltransferases ; Humans ; Isoelectric Focusing ; Mass Spectrometry ; *Membrane Proteins ; Molecular Sequence Data ; Monocytes/enzymology ; N-Acetylglucosaminyltransferases/deficiency/*genetics/metabolism ; Point Mutation ; Polysaccharides/biosynthesis ; Psychomotor Disorders/diagnosis ; Transferases/metabolism ; Transferrin/analysis/chemistry/genetics ; }, abstract = {The carbohydrate-deficient glycoprotein syndromes (CDGS) are a group of autosomal recessive multisystemic diseases characterized by defective glycosylation of N-glycans. This review describes recent findings on two patients with CDGS type II. In contrast to CDGS type I, the type II patients show a more severe psychomotor retardation, no peripheral neuropathy and a normal cerebellum. The CDGS type II serum transferrin isoelectric focusing pattern shows a large amount (95%) of disialotransferrin in which each of the two glycosylation sites is occupied by a truncated monosialo-monoantennary N-glycan. Fine structure analysis of this glycan suggested a defect in the Golgi enzyme UDP-GlcNAc:alpha-6-D-mannoside beta-1,2-N-acetylglucosaminyltransferase II (GnT II; EC 2.4.1.143) which catalyzes an essential step in the biosynthetic pathway leading from hybrid to complex N-glycans. GnT II activity is reduced by over 98% in fibroblast and mononuclear cell extracts from the CDGS type II patients. Direct sequencing of the GnT II coding region from the two patients identified two point mutations in the catalytic domain of GnT II, S290F (TCC to TTC) and H262R (CAC to CGC). Either of these mutations inactivates the enzyme and probably also causes reduced expression. The CDG syndromes and other congenital defects in glycan synthesis as well as studies of null mutations in the mouse provide strong evidence that the glycan moieties of glycoproteins play essential roles in the normal development and physiology of mammals and probably of all multicellular organisms.}, } @article {pmid10570989, year = {1999}, author = {Patthy, L}, title = {Genome evolution and the evolution of exon-shuffling--a review.}, journal = {Gene}, volume = {238}, number = {1}, pages = {103-114}, doi = {10.1016/s0378-1119(99)00228-0}, pmid = {10570989}, issn = {0378-1119}, mesh = {Animals ; *Evolution, Molecular ; *Exons ; *Genome ; }, abstract = {Recent studies on the genomes of protists, plants, fungi and animals confirm that the increase in genome size and gene number in different eukaryotic lineages is paralleled by a general decrease in genome compactness and an increase in the number and size of introns. It may thus be predicted that exon-shuffling has become increasingly significant with the evolution of larger, less compact genomes. To test the validity of this prediction, we have analyzed the evolutionary distribution of modular proteins that have clearly evolved by intronic recombination. The results of this analysis indicate that modular multidomain proteins produced by exon-shuffling are restricted in their evolutionary distribution. Although such proteins are present in all major groups of metazoa from sponges to chordates, there is practically no evidence for the presence of related modular proteins in other groups of eukaryotes. The biological significance of this difference in the composition of the proteomes of animals, fungi, plants and protists is best appreciated when these modular proteins are classified with respect to their biological function. The majority of these proteins can be assigned to functional categories that are inextricably linked to multicellularity of animals, and are of absolute importance in permitting animals to function in an integrated fashion: constituents of the extracellular matrix, proteases involved in tissue remodelling processes, various proteins of body fluids, membrane-associated proteins mediating cell-cell and cell-matrix interactions, membrane associated receptor proteins regulating cell cell communications, etc. Although some basic types of modular proteins seem to be shared by all major groups of metazoa, there are also groups of modular proteins that appear to be restricted to certain evolutionary lineages. In summary, the results suggest that exon-shuffling acquired major significance at the time of metazoan radiation. It is interesting to note that the rise of exon-shuffling coincides with a spectacular burst of evolutionary creativity: the Big Bang of metazoan radiation. It seems probable that modular protein evolution by exon-shuffling has contributed significantly to this accelerated evolution of metazoa, since it facilitated the rapid construction of multidomain extracellular and cell surface proteins that are indispensable for multicellularity.}, } @article {pmid10561504, year = {1999}, author = {Quesada, V and Ponce, MR and Micol, JL}, title = {OTC and AUL1, two convergent and overlapping genes in the nuclear genome of Arabidopsis thaliana.}, journal = {FEBS letters}, volume = {461}, number = {1-2}, pages = {101-106}, doi = {10.1016/s0014-5793(99)01426-x}, pmid = {10561504}, issn = {0014-5793}, mesh = {Adaptor Proteins, Vesicular Transport ; Amino Acid Sequence ; Arabidopsis/*genetics ; *Arabidopsis Proteins ; Base Sequence ; Cell Nucleus/*genetics ; DNA, Bacterial/genetics/metabolism ; DNA, Complementary/metabolism ; Genes, Overlapping ; Genome, Plant ; Models, Genetic ; Molecular Sequence Data ; Mutagenesis ; Nerve Tissue Proteins/*genetics ; Ornithine Carbamoyltransferase/*genetics ; Phenotype ; Phosphoproteins/*genetics ; Phylogeny ; Plant Proteins/*genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription, Genetic ; }, abstract = {In contrast to bacterial, fungal and vertebrate ornithine transcarbamylases (OTCs; EC 2.1.3.3), very little is known about the enzyme in plants. We report here the isolation of a T-DNA-tagged mutant displaying sensitivity to ornithine, whose characterization has allowed for the identification of several complementary and genomic DNA clones encoding the OTC and auxilin-like 1 (AUL1) proteins of the crucifer Arabidopsis thaliana. Transcript mapping revealed that at least 22 bp within the OTC-AUL1 intercoding region are transcribed from both strands, which makes this one of the rarely described cases of convergent and overlapping transcription units in the nuclear genome of a multicellular eukaryote. Transcription of the OTC gene was shown to be ubiquitous in aerial organs of adult plants, whereas that of AUL1 was obscured by the existence of a putative second copy of the gene. The OTC-AUL1 locus maps at the bottom of chromosome 1.}, } @article {pmid10542368, year = {1999}, author = {Mohri, H and Inaba, K and Kubo-Irie, M and Takai, H and Yano-Toyoshima, Y}, title = {Characterization of outer arm dynein in sea anemone, Anthopleura midori.}, journal = {Cell motility and the cytoskeleton}, volume = {44}, number = {3}, pages = {202-208}, doi = {10.1002/(SICI)1097-0169(199911)44:3<202::AID-CM5>3.0.CO;2-E}, pmid = {10542368}, issn = {0886-1544}, mesh = {Animals ; Dyneins/*chemistry/isolation & purification/physiology/ultrastructure ; Male ; Phylogeny ; Sea Anemones/classification/*enzymology ; Sperm Tail/ultrastructure ; }, abstract = {Outer arm dynein was purified from sperm flagella of a sea anemone, Anthopleura midori, and its biochemical and biophysical properties were characterized. The dynein, obtained at a 20S ATPase peak by sucrose density gradient centrifugation, consisted of two heavy chains, three intermediate chains, and seven light chains. The specific ATPase activity of dynein was 1.3 micromol Pi/mg/min. Four polypeptides (296, 296, 225, and 206 kDa) were formed by UV cleavage at 365 nm of dynein in the presence of vanadate and ATP. In addition, negatively stained images of dynein molecules and the hook-shaped image of the outer arm of the flagella indicated that sea anemone outer arm dynein is two-headed. In contrast to protist dyneins, which are three-headed, outer arm dyneins of flagella and cilia in multicellular animals are two-headed molecules corresponding to the two heavy chains. Phylogenetic considerations were made concerning the diversity of outer arm dyneins.}, } @article {pmid10541655, year = {1999}, author = {Burmester, T and Scheller, K}, title = {Ligands and receptors: common theme in insect storage protein transport.}, journal = {Die Naturwissenschaften}, volume = {86}, number = {10}, pages = {468-474}, doi = {10.1007/s001140050656}, pmid = {10541655}, issn = {0028-1042}, mesh = {Amino Acid Sequence ; Animals ; Insect Hormones/*physiology ; Insecta ; *Ligands ; Molecular Sequence Data ; Receptors, Cell Surface/chemistry/*physiology ; Signal Transduction ; }, abstract = {The passage of macromolecules through biological membranes is an essential process for all multicellular organisms. Insects have developed a mechanism different from that known for all other eukaryotes investigated so far. This review discusses the function and evolution of this mechanism. Insect pupae do not feed during metamorphosis. Therefore they depend on material that has been accumulated during the larval life. At the end of this period, shortly before pupariation, a rise in titer of ecdysteroid hormones induces the incorporation of a large fraction of storage proteins (hexamerins) from the body fluid into the fat body cells. The transport of hexamerins across the cell-membrane is mediated by a specific ecdysteroid-controlled receptor. It is synthesized as a precursor protein that is subsequently processed into the active receptor. This receptor protein is very unusual because it is closely related to its own hexamerin ligand. Sequence comparison shows that the hexamerins and hexamerin receptors diverged early in insect evolution and derive from a common hemocyanin ancestor.}, } @article {pmid10527926, year = {1999}, author = {Baldauf, SL}, title = {A Search for the Origins of Animals and Fungi: Comparing and Combining Molecular Data.}, journal = {The American naturalist}, volume = {154}, number = {S4}, pages = {S178-S188}, doi = {10.1086/303292}, pmid = {10527926}, issn = {1537-5323}, abstract = {Green plants, animals, and fungi have long held our interest as complex, largely multicellular eukaryotes of indeterminate origin. Considerable progress has now been made toward understanding the evolutionary relationships among these taxa as well as identifying their closest protistan relatives. An exclusive animal-fungal clade (the Opisthokonta) is now widely accepted based on an insertion in the protein synthesis elongation factor 1alpha (EF-1alpha) and molecular phylogenies of ribosomal RNAs and the conservative proteins actin, alpha-tubulin, beta-tubulin, and EF-1alpha. Protein data also suggest that the cellular (dictyostelid) and acellular (myxogastrid) slime molds are a close outgroup to the animal-fungal clade. Subsequent sequencing and phylogenetic analysis of EF-1alpha sequences very strongly support a monophyletic slime mold clade (the Mycetozoa or Eumycetozoa), which also includes the lesser-known protostelid slime molds. Monophyly of the opisthokont and mycetozoan clades, exclusive of green plants, is suggested by individual analyses of EF-1alpha and actin and given strong support by concatenated protein data. Neither the monophyly of the slime molds nor their close relationship to animals and fungi are consistently supported by ribosomal RNA data. Thus, it appears unlikely that any single molecule will accurately reconstruct all higher-order taxonomy.}, } @article {pmid10525735, year = {1999}, author = {Fukui, M and Teske, A and Assmus, B and Muyzer, G and Widdel, F}, title = {Physiology, phylogenetic relationships, and ecology of filamentous sulfate-reducing bacteria (genus desulfonema).}, journal = {Archives of microbiology}, volume = {172}, number = {4}, pages = {193-203}, doi = {10.1007/s002030050760}, pmid = {10525735}, issn = {1432-072X}, abstract = {Microscopy of organic-rich, sulfidic sediment samples of marine and freshwater origin revealed filamentous, multicellular microorganisms with gliding motility. Many of these neither contained sulfur droplets such as the Beggiatoa species nor exhibited the autofluorescence of the chlorophyll-containing cyanobacteria. A frequently observed morphological type of filamentous microorganism was enriched under anoxic conditions in the dark with isobutyrate plus sulfate. Two strains of filamentous, gliding sulfate-reducing bacteria, Tokyo 01 and Jade 02, were isolated in pure cultures. Both isolates oxidized acetate and other aliphatic acids. Enzyme assays indicated that the terminal oxidation occurs via the anaerobic C(1) pathway (carbon monoxide dehydrogenase pathway). The 16S rRNA genes of the new isolates and of the two formerly described filamentous species of sulfate-reducing bacteria, Desulfonema limicola and Desulfonema magnum, were analyzed. All four strains were closely related to each other and affiliated with the delta-subclass of Proteobacteria. Another close relative was the unicellular Desulfococcus multivorans. Based on phylogenetic relationships and physiological properties, Strains Tokyo 01 and Jade 02 are assigned to a new species, Desulfonema ishimotoi. A new, fluorescently labeled oligonucleotide probe targeted against 16S rRNA was designed so that that it hybridized specifically with whole cells of Desulfonema species. Filamentous bacteria that hybridized with the same probe were detected in sediment samples and in association with the filamentous sulfur-oxidizing bacterium Thioploca in its natural habitat. We conclude that Desulfonema species constitute an ecologically significant fraction of the sulfate-reducing bacteria in organic-rich sediments and microbial mats.}, } @article {pmid10523521, year = {1999}, author = {Bowen, NJ and McDonald, JF}, title = {Genomic analysis of Caenorhabditis elegans reveals ancient families of retroviral-like elements.}, journal = {Genome research}, volume = {9}, number = {10}, pages = {924-935}, doi = {10.1101/gr.9.10.924}, pmid = {10523521}, issn = {1088-9051}, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans/*genetics ; Evolution, Molecular ; Gene Products, env/genetics ; *Genome ; Models, Genetic ; Molecular Sequence Data ; Open Reading Frames ; Phylogeny ; RNA-Directed DNA Polymerase/genetics ; Retroelements/*genetics ; Retroviridae/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {Retrotransposons are the most abundant and widespread class of eukaryotic transposable elements. The recent genome sequencing of Caenorhabditis elegans has provided an unprecedented opportunity to analyze the evolutionary relationships among the entire complement of retrotransposons within a multicellular eukaryotic organism. In this article we report the results of an analysis of retroviral-like long terminal repeat retrotransposons in C. elegans that indicate that this class of elements may be even more abundant and divergent than previously expected. The unexpected presence, in C. elegans, of an element displaying a number of characteristics previously thought to be unique to vertebrate retroviruses suggests an ancient lineage for this important class of infectious agents.}, } @article {pmid10521526, year = {1999}, author = {Serino, G and Tsuge, T and Kwok, S and Matsui, M and Wei, N and Deng, XW}, title = {Arabidopsis cop8 and fus4 mutations define the same gene that encodes subunit 4 of the COP9 signalosome.}, journal = {The Plant cell}, volume = {11}, number = {10}, pages = {1967-1980}, pmid = {10521526}, issn = {1040-4651}, mesh = {Alleles ; Animals ; Arabidopsis/*genetics ; *Arabidopsis Proteins ; COP9 Signalosome Complex ; Chromatography, Affinity ; Chromosome Mapping ; Cloning, Molecular ; *Genes, Plant ; Humans ; Molecular Sequence Data ; Multiprotein Complexes ; *Mutation ; Peptide Hydrolases ; Phenotype ; Phylogeny ; Plant Proteins/*genetics/isolation & purification/metabolism ; *Proteins ; Sequence Homology, Amino Acid ; *Signal Transduction ; }, abstract = {The pleiotropic constitutive photomorphogenic/deetiolated/fusca (cop/det/fus) mutants of Arabidopsis exhibit features of light-grown seedlings when grown in the dark. Cloning and biochemical analysis of COP9 have revealed that it is a component of a multiprotein complex, the COP9 signalosome (previously known as the COP9 complex). Here, we compare the immunoaffinity and the biochemical purification of the COP9 signalosome from cauliflower and confirm its eight-subunit composition. Molecular cloning of subunit 4 of the complex revealed that it is a proteasome-COP9 complex-eIF3 domain protein encoded by a gene that maps to chromosome 5, near the chromosomal location of the cop8 and fus4 mutations. Genetic complementation tests showed that the cop8 and fus4 mutations define the same locus, now designated as COP8. Molecular analysis of the subunit 4-encoding gene in both cop8 and fus4 mutants identified specific molecular lesions, and overexpression of the subunit 4 cDNA in a cop8 mutant background resulted in complete rescue of the mutant phenotype. Thus, we conclude that COP8 encodes subunit 4 of the COP9 signalosome. Examination of possible molecular interactions by using the yeast two-hybrid assay indicated that COP8 is capable of strong self-association as well as interaction with COP9, FUS6/COP11, FUS5, and Arabidopsis JAB1 homolog 1, the latter four proteins being previously defined subunits of the Arabidopsis COP9 signalosome. A comparative sequence analysis indicated that COP8 is highly conserved among multicellular eukaryotes and is also similar to a subunit of the 19S regulatory particle of the 26S proteasome.}, } @article {pmid10516290, year = {1999}, author = {Pavlova, A and Stuart, RO and Pohl, M and Nigam, SK}, title = {Evolution of gene expression patterns in a model of branching morphogenesis.}, journal = {The American journal of physiology}, volume = {277}, number = {4}, pages = {F650-63}, doi = {10.1152/ajprenal.1999.277.4.F650}, pmid = {10516290}, issn = {0002-9513}, support = {DK-02392/DK/NIDDK NIH HHS/United States ; DK-49517/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Autoradiography ; Cell Differentiation ; Cell Line ; Culture Media, Conditioned/pharmacology ; Culture Techniques ; DNA, Complementary/genetics ; Embryo, Mammalian/cytology/drug effects/*physiology ; Embryonic and Fetal Development ; Extracellular Matrix/physiology ; *Gene Expression Regulation, Developmental ; Mice ; Oligonucleotide Array Sequence Analysis ; Ureter/*embryology ; }, abstract = {Branching morphogenesis of the ureteric bud in response to unknown signals from the metanephric mesenchyme gives rise to the urinary collecting system and, via inductive signals from the ureteric bud, to recruitment of nephrons from undifferentiated mesenchyme. An established cell culture model for this process employs cells of ureteric bud origin (UB) cultured in extracellular matrix and stimulated with conditioned media (BSN-CM) from a metanephric mesenchymal cell line (H. Sakurai, E. J. Barros, T. Tsukamoto, J. Barasch, and S. K. Nigam. Proc. Natl. Acad. Sci. USA 94: 6279-6284, 1997.). In the presence of BSN-CM, the UB cells form branching tubular structures reminiscent of the branching ureteric bud. The pattern of gene regulation in this model of branching morphogenesis of the kidney collecting system was investigated using high-density cDNA arrays. Software and analytical methods were developed for the quantification and clustering of genes. With the use of a computational method termed "vector analysis," genes were clustered according to the direction and magnitude of differential expression in n-dimensional log-space. Changes in gene expression in response to the BSN-CM consisted primarily of differential expression of transcription factors with previously described roles in morphogenesis, downregulation of pro-apoptotic genes accompanied by upregulation of anti-apoptotic genes, and upregulation of a small group of secreted products including growth factors, cytokines, and extracellular proteinases. Changes in expression are discussed in the context of a general model for epithelial branching morphogenesis. In addition, the cDNA arrays were used to survey expression of epithelial markers and secreted factors in UB and BSN cells, confirming the largely epithelial character of the former and largely mesenchymal character of the later. Specific morphologies (cellular processes, branching multicellular cords, etc.) were shown to correlate with the expression of different, but overlapping, genomic subsets, suggesting differences in morphogenetic mechanisms at these various steps in the evolution of branching tubules.}, } @article {pmid10508976, year = {1999}, author = {Gerhart, J}, title = {1998 Warkany lecture: signaling pathways in development.}, journal = {Teratology}, volume = {60}, number = {4}, pages = {226-239}, doi = {10.1002/(SICI)1096-9926(199910)60:4<226::AID-TERA7>3.0.CO;2-W}, pmid = {10508976}, issn = {0040-3709}, support = {GM19363/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Embryonic and Fetal Development/*physiology ; Gastrula/physiology ; Humans ; Models, Biological ; Morphogenesis/*physiology ; Signal Transduction/*physiology ; Vertebrates ; }, abstract = {Cell-cell signaling pervades all aspects of development, not just in vertebrates, but in all animals (metazoa). It is a typifying characteristic of the major multicellular life forms, animals, plants, and fungi, which diverged about 1.2 billion years ago from a common ancestor descended from a lineage of unicellular life forms. In metazoa, at least 17 kinds of signal transduction pathways operate, each distinguished by its transduction intermediates. Five kinds predominate in early embryonic development, namely, the Wnt, TGF-beta, Hedgehog, RTK, and Notch pathways. Five more are used in late development, and seven more in the functions of differentiated cells. The pathways must have evolved and become conserved in pre-Cambrian times before the divergence of basal members of most of the modern phyla. In metazoan development and physiology, the responses of cells to intercellular signals include cell proliferation, secretion, motility, and transcription. These responses tend to be conserved among metazoa and shared with unicellular eukaryotes and in some cases even with unicellular prokaryotes. Protein components of the responses date back 2 billion years to ancestral eukaryotes or 3 billion to ancestral prokaryotes. Each metazoan developmental process consists of a network of signals and responses, and many of these networks are conserved among metazoa, for example, by insects and mammals. The study of model organisms, even of nonvertebrate groups, is expected to continue to contribute greatly to the understanding of mammalian development and to offer opportunities to analyze the effects of toxicants on development, as well as opportunities to devise incisive assays for toxicants.}, } @article {pmid10508589, year = {1999}, author = {Cikala, M and Wilm, B and Hobmayer, E and Böttger, A and David, CN}, title = {Identification of caspases and apoptosis in the simple metazoan Hydra.}, journal = {Current biology : CB}, volume = {9}, number = {17}, pages = {959-962}, doi = {10.1016/s0960-9822(99)80423-0}, pmid = {10508589}, issn = {0960-9822}, mesh = {Animals ; Apoptosis/drug effects/*physiology ; Binding Sites ; Caenorhabditis elegans Proteins ; Caspase 3 ; Caspases/analysis/chemistry/genetics/*physiology ; Colchicine/pharmacology ; Cysteine Endopeptidases/chemistry ; Evolution, Molecular ; Helminth Proteins/chemistry ; Humans ; Hydra/cytology/drug effects/*enzymology/genetics ; Phagocytosis ; Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {Apoptosis is a normal process by which cells die and are eliminated from tissue by phagocytosis [1]. It is involved in regulating cell numbers in adult tissues and in eliminating 'excess' cells during embryogenesis and development. Apoptosis is mediated by activation of caspases, which then cleave a variety of cellular substrates and thereby cause the characteristic morphology of apoptotic cells (rounded cells, condensed chromatin, susceptibility to phagocytosis) [2]. Although apoptosis has been well documented in nematodes, insects and mammals, it is not yet clear how early in evolution apoptosis or its component enzymes arose. In the simple metazoan Hydra vulgaris, cell death regulates cell numbers [3] [4] [5]. In starved animals, for example, epithelial cell proliferation continues at a nearly normal rate although the tissue does not increase in size; the excess cells produced are eliminated by phagocytosis. Cell death can also be induced in wild-type hydra by treatment with colchicine [6] or in a mutant strain (sf-1) by temperature shock [7]. Here, we show that cell death in hydra is morphologically indistinguishable from apoptosis in higher animals, that hydra polyps express two genes with strong homology to members of the caspase 3 family, and that caspase-3-specific enzyme activity accompanies apoptosis in hydra. The occurrence of apoptosis and caspases in a member of the ancient metazoan phylum Cnidaria supports the idea that the invention of apoptosis was an essential feature of the evolution of multicellular animals.}, } @article {pmid10503188, year = {2000}, author = {Nanney, DL and Simon, EM}, title = {Laboratory and evolutionary history of Tetrahymena thermophila.}, journal = {Methods in cell biology}, volume = {62}, number = {}, pages = {3-25}, doi = {10.1016/s0091-679x(08)61527-7}, pmid = {10503188}, issn = {0091-679X}, mesh = {Animals ; Breeding ; *Evolution, Molecular ; Tetrahymena thermophila/classification/*genetics/immunology/physiology ; }, abstract = {An account is given of the early efforts to domesticate tetrahymenas as laboratory instruments for genetics. The rationale for developing a new organismic technology was the comparative leverage provided by a eukaryotic microorganism at a large evolutionary distance from both prokaryotic microbes and multicellular organisms. The tetrahymenine ciliates were considered more favorable materials than paramecia because of their ability to grow on simple media, though in fact their simpler nutritional needs have never been fully exploited. The first task was to sort the large set of phenotypically similar but evolutionarily and molecularly diverse ciliates referred to at the time as T. pyriformis. Then a species amenable to genetic manipulation was identified and its culture and cytogenetics were brought under control. Fortunately, the very first breeding system investigated--that in the species now called T. thermophila--has proved to be suitable for a wide range of studies. A large factor in the program's success was its use of the foundation previously established by studies on paramecia. However, serious unforeseen difficulties were encountered on the way to "domestication." These included inbreeding deterioration associated with their outbreeding life-style and germinal deterioration (mutational erosion) in the unexpressed micronuclear genome after long maintenance in vegetative culture. Cryogenic preservation was an important means of escaping these organismic limitations, and somatic (macronuclear) assortment has proved a valuable supplement to meiotic recombination.}, } @article {pmid10497319, year = {1999}, author = {Hilscher, W}, title = {Some remarks on the female and male Keimbahn in the light of evolution and history.}, journal = {The Journal of experimental zoology}, volume = {285}, number = {3}, pages = {197-214}, pmid = {10497319}, issn = {0022-104X}, mesh = {Animals ; *Biological Evolution ; Cell Differentiation ; Eukaryota ; Female ; Germ Cells/*growth & development/physiology ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; Humans ; Insecta/anatomy & histology ; Male ; Mammals/anatomy & histology ; *Oogenesis ; Plants/anatomy & histology ; *Spermatogenesis ; }, abstract = {From the existence of two types of cells for reproduction-the female and male germ cells (GCs)-and by recombination of the genome, evolution proceeded dramatically. Unicellular and multicellular plants frequently are characterized by a sequence of haploid and diploid phases, or generations, with gametes and spores as reproductive cells. Isogamy, anisogamy, and oogamy can be distinguished depending on the GCs that correspond, differ in size, or impose as egg cell and sperm cell. In protozoans, too, species are found in which GCs differ clearly from each other. In the female lineage of angiosperms, a "Keimbahn chain" consisting of five successive germ line cells can be observed. Oogenesis and spermatogenesis are complete in coelenterates and similar in mammals. However, the controlling mechanisms are by far more complex in the latter. This means that the balance of hormonal and vegetative nervous influences (stimulation, inhibition) on gametogenesis is not primarily orientated on the germ line cells themselves, but mostly on the structural and functional situation of the gonads and the individual carriers. This becomes particularly evident in insects, where gametogenesis, on the one side, depends on the development of the rest of the organism but on the other side represents an independent developmental process. The point at which germ line cells and somatic cells separate correlates more or less with the degree of phylogenetic development. In worms, insects, and up to the anurans, a part of the cytoplasm, the so-called germ plasma, is separated for the development of GCs during oogenesis (preformistic development). However, in urodeles, reptiles, birds, and mammals, GCs and somatic cells cannot be distinguished before gastrulation (epigenetic development). In various species (e.g., in some oligochaetes and snails), there exist "double spermatogenic lines." In mammals (probably in other vertebrates and perhaps in various phyla of animals, too), the female Keimbahn is provided with only one proliferation system. The male gametogenesis is equipped with two systems: the first corresponds to the female germ line, the second is responsible for the immense number of gametes produced in the mature testes. In mammals the message to become male lies on the Y-chromosome (on its short arm in man and mouse) and was identified as the gene SRY in human and Sry in mouse. The fertility genes that are responsible for an uninterrupted spermatogenesis, up to fertilizing spermatozoa, are sitting on the long arm of the human Y-chromosome. J. Exp. Zool. (Mol. Dev. Evol.) 285:197-214, 1999.}, } @article {pmid10491567, year = {1999}, author = {Mattson, MP and Bruce-Keller, AJ}, title = {Compartmentalization of signaling in neurons: evolution and deployment.}, journal = {Journal of neuroscience research}, volume = {58}, number = {1}, pages = {2-9}, pmid = {10491567}, issn = {0360-4012}, mesh = {Animals ; *Biological Evolution ; Cell Communication ; Humans ; Neurons/*physiology ; Signal Transduction/*physiology ; Synapses/*physiology ; }, abstract = {The localization of signal transduction machinery at synapses is a fundamental organizational feature of the nervous system that allows for highly complex integration of information coding processes. Synaptic communication evolved as multicellular organisms became more complex, and as selection pressures were placed on such organisms such that those capable of responding rapidly and specifically to environmental demands survived. Two obvious advantages of synaptic transmission (as opposed to endocrine or paracrine signaling) are that it provides for rapid intercellular communication over great distances and that it provides a high level of spatial specificity. There are several structural and functional aspects of synapses that set them apart from other cellular compartments, with many of the specializations subserving roles in synaptic signal transduction (e.g., neurotransmitter release from the presynaptic terminal and postsynaptic receptor activation and second messenger production). However, studies of developing nervous systems have shown that many synaptic signaling mechanisms are operative prior to synaptogenesis and play important roles in regulating growth cone behaviors, synaptogenesis, and even programmed cell death. Indeed, the concept that "ontogeny recapitulates phylogeny" can be effectively applied to the evolution of the synapse. As the embryo rapidly grows, neurons must elaborate axons and dendrites, establish functional synaptic connections, and maintain and adjust those connections as the organism matures. The purpose of this introductory article is to set the stage for the following articles by briefly reviewing fundamental aspects of the molecular and cellular biology of synapses in an evolutionary context.}, } @article {pmid10468603, year = {1999}, author = {Jelesko, JG and Harper, R and Furuya, M and Gruissem, W}, title = {Rare germinal unequal crossing-over leading to recombinant gene formation and gene duplication in Arabidopsis thaliana.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {96}, number = {18}, pages = {10302-10307}, pmid = {10468603}, issn = {0027-8424}, mesh = {Arabidopsis/*genetics ; Base Sequence ; *Crossing Over, Genetic ; DNA Primers ; Exons ; *Gene Duplication ; Gene Expression Regulation, Plant ; Genes, Plant ; Genes, Synthetic ; Molecular Sequence Data ; Multigene Family ; Polymerase Chain Reaction ; Protein Biosynthesis ; Recombinant Fusion Proteins/genetics ; Recombination, Genetic ; Ribulose-Bisphosphate Carboxylase/*genetics ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Transcription, Genetic ; }, abstract = {Small, multigene families organized in a tandem array can facilitate the rapid evolution of the gene cluster by a process of meiotic unequal crossing-over. To study this process in a multicellular organism, we created a synthetic RBCSB gene cluster in Arabidopsis thaliana and used this to measure directly the frequency of meiotic, intergenic unequal crossing-over between sister chromatids. The synthetic RBCSB gene cluster was composed of a silent DeltaRBCS1B::LUC chimeric gene fusion, lacking all 5' transcription and translation signals, followed by RBCS2B and RBC3B genomic DNA. Expression of luciferase activity (luc(+)) required a homologous recombination event between the DeltaRBCS1B::LUC and the RBCS3B genes, yielding a novel recombinant RBCS3B/ 1B::LUC chimeric gene whose expression was driven by RBCS3B 5' transcription and translation signals. Using sensitive, single-photon-imaging equipment, three luc(+) seedlings were identified in more than 1 million F2 seedlings derived from self-fertilized F1 plants hemizygous for the synthetic RBCSB gene cluster. The F2 luc(+) seedlings were isolated, and molecular and genetic analysis indicated that the luc(+) trait was caused by the formation of a recombinant chimeric RBCS3B/1B::LUC gene. A predicted duplication of the RBCS2B gene also was present. The recombination resolution break points mapped adjacent to a region of intron I at which a disjunction in sequence similarity between RBCS1B and RBCS3B occurs; this provided evidence supporting models of gene cluster evolution by exon-shuffling processes. In contrast to most measures of meiotic unequal crossing-over that require the deletion of a gene in a gene cluster, these results directly measured the frequency of meiotic unequal crossing-over (approximately 3 x 10(-6)), leading to the expansion of the gene cluster and the formation of a novel recombinant gene.}, } @article {pmid10455418, year = {1999}, author = {Boyd, M and Cunningham, SH and Brown, MM and Mairs, RJ and Wheldon, TE}, title = {Noradrenaline transporter gene transfer for radiation cell kill by 131I meta-iodobenzylguanidine.}, journal = {Gene therapy}, volume = {6}, number = {6}, pages = {1147-1152}, doi = {10.1038/sj.gt.3300905}, pmid = {10455418}, issn = {0969-7128}, mesh = {3-Iodobenzylguanidine/*metabolism ; Antineoplastic Agents/*therapeutic use ; Carrier Proteins/*genetics ; Cell Division ; Cell Survival ; Dose-Response Relationship, Drug ; Gene Transfer Techniques ; Glioblastoma/pathology/*radiotherapy ; Humans ; Norepinephrine Plasma Membrane Transport Proteins ; Radiopharmaceuticals/*therapeutic use ; *Symporters ; Tumor Cells, Cultured ; }, abstract = {Meta-iodobenzylguanidine conjugated to 131I-iodine is an effective agent for the targeted radiotherapy of tumors of neural crest origin which express the noradrenaline transporter (NAT). The therapeutic application of 131I MIBG is presently limited to the treatment of phaeochromocytoma, neuroblastoma, carcinoid and medullary thyroid carcinoma. To determine the feasibility of MIBG targeting for a wider range of tumor types, we employed plasmid-mediated transfer of the NAT gene into a human glioblastoma cell line (UVW) which does not express the NAT gene. This resulted in a 15-fold increase in uptake of MIBG by the host cells. A dose-dependent toxicity of 131I MIBG to the transfectants was demonstrated using three methods: (1) survival of clonogens derived from monolayer culture; (2) survival of clonogens derived from disaggregated multicellular spheroids; and (3) spheroid growth delay. 131I MIBG was twice as toxic to cells in spheroids compared with those in monolayers, consistent with a greater effect of radiation cross-fire (radiological bystander effect) from 131I beta-radiation in the three-dimensional tumor spheroids. The highest concentration of 131I MIBG tested (1 MBq/ml) was nontoxic to UVW control cells or spheroids transfected with the NAT gene in reverse orientation. These findings are encouraging for the development of NAT gene transfer-mediated 131I MIBG therapy.}, } @article {pmid10449581, year = {1999}, author = {Ebnet, E and Fischer, M and Deininger, W and Hegemann, P}, title = {Volvoxrhodopsin, a light-regulated sensory photoreceptor of the spheroidal green alga Volvox carteri.}, journal = {The Plant cell}, volume = {11}, number = {8}, pages = {1473-1484}, pmid = {10449581}, issn = {1040-4651}, mesh = {*Algal Proteins ; Amino Acid Sequence ; Antisense Elements (Genetics) ; Base Sequence ; Chlorophyta/*genetics/*radiation effects ; DNA, Complementary/genetics ; Evolution, Molecular ; *Gene Expression Regulation, Plant ; *Genes, Plant ; Membrane Proteins/*metabolism ; Molecular Sequence Data ; RNA, Messenger/isolation & purification ; Recombinant Proteins/biosynthesis ; Rod Opsins/classification/genetics ; Schizosaccharomyces/genetics ; Sequence Homology, Amino Acid ; Signal Transduction ; Transformation, Genetic ; }, abstract = {Somatic cells of the multicellular alga Volvox carteri contain a visual rhodopsin that controls the organism's phototactic behavior via two independent photoreceptor currents. Here, we report the identification of an opsinlike gene, designated as volvoxopsin (vop). The encoded protein exhibits homologies to the opsin of the unicellular alga Chlamydomonas reinhardtii (chlamyopsin) and to the entire animal opsin family, thus providing new perspectives on opsin evolution. Volvoxopsin accumulates within the eyes of somatic cells. However, the vop transcript is detectable only in the reproductive eyeless gonidia and embryos. vop mRNA levels increase 400-fold during embryogenesis, when embryos develop in darkness, whereas the vop transcript does not accumulate when embryos develop in the light. An antisense transformant, T3, was generated. This transformant produces 10 times less volvoxopsin than does the wild type. In T3, the vop transcript is virtually absent, whereas the antisense transcript is predominant and light regulated. It follows that vop expression is under light-dependent transcriptional control but that volvoxopsin itself is not the regulatory photoreceptor. Transformant T3 is phototactic, but its phototactic sensitivity is reduced 10-fold relative to the parental wild-type strain HK10. Thus, we offer definitive genetic evidence that a rhodopsin serves as the photoreceptor for phototaxis in a green alga.}, } @article {pmid10433974, year = {1999}, author = {Sommer, P and Blin, N and Gött, P}, title = {Tracing the evolutionary origin of the TFF-domain, an ancient motif at mucous surfaces.}, journal = {Gene}, volume = {236}, number = {1}, pages = {133-136}, doi = {10.1016/s0378-1119(99)00243-7}, pmid = {10433974}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Animals ; Chromosome Mapping ; Chromosomes, Human, Pair 21 ; *Evolution, Molecular ; Exons ; Growth Substances/*genetics ; Humans ; Molecular Sequence Data ; *Mucins ; *Muscle Proteins ; *Neuropeptides ; Peptides/*genetics ; Sequence Homology, Amino Acid ; Trefoil Factor-2 ; Trefoil Factor-3 ; Urochordata/genetics ; }, abstract = {Mammalian trefoil factor family (TFF)-domain peptides promote gastrointestinal protection, healing and cell migration and may act as tumour suppressors. TFF-like domains also constitute modules of composite proteins like mucin glycoproteins and zona pellucida proteins. Database searches with a modified, less stringent consensus sequence - C-x(5,6)-[ST]-x(3)-C-x(4,5)-C-C-[FYWH]-x(2, 24)-C-[FY] - revealed that ancestors of the TFF-domain arose before amphibian evolution. Eggshell proteins and a zona pellucida-like protein in teleost species, an epidermis-specific protein in a tunicate as well as an open reading frame in a nematode exhibited TFF-like motifs suggesting that they most likely originated in some multicellular organism.}, } @article {pmid10421676, year = {1999}, author = {Bull, L}, title = {On the evolution of multicelluarity and eusociality.}, journal = {Artificial life}, volume = {5}, number = {1}, pages = {1-15}, doi = {10.1162/106454699568656}, pmid = {10421676}, issn = {1064-5462}, mesh = {Algorithms ; Animals ; *Biological Evolution ; Cell Aggregation ; Cell Differentiation ; *Models, Biological ; Reproduction ; Social Behavior ; }, abstract = {In this article versions of the abstract NKC model are used to examine the conditions under which two significant evolutionary phenomena - multicellularity and eusociality - are likely to occur and why. First, comparisons in evolutionary performance are made between simulations of unicellular organisms and very simple multicellular-like organisms, under varying conditions. The results show that such multicellularity without differentiation appears selectively neutral, but that differentiation to soma (nonreproductives) proves beneficial as the amount of epistasis in the fitness landscape increases. This is explained by considering mutations in the generation of daughter cells and their subsequent effect on the propagule's fitness. This is interpreted as a simple example of the Baldwin effect. Second, the correspondences between multicellularity and eusociality are highlighted, particularly that both contain individuals who do not reproduce. The same process is then used to explain the emergence of eusocial colonies.}, } @article {pmid10411094, year = {1999}, author = {Durek, C and Brandau, S and Ulmer, AJ and Flad, HD and Jocham, D and Böhle, A}, title = {Bacillus-Calmette-Guérin (BCG) and 3D tumors: an in vitro model for the study of adhesion and invasion.}, journal = {The Journal of urology}, volume = {162}, number = {2}, pages = {600-605}, doi = {10.1016/s0022-5347(05)68633-8}, pmid = {10411094}, issn = {0022-5347}, mesh = {Adjuvants, Immunologic/*pharmacology ; BCG Vaccine/*pharmacology ; Cell Adhesion ; Humans ; Neoplasm Invasiveness ; Spheroids, Cellular/*pathology ; Tumor Cells, Cultured ; Urinary Bladder Neoplasms/*pathology ; }, abstract = {PURPOSE: To study adhesion, penetration and internalization of BCG and effector-cells to and into three-dimensional in vitro cell aggregates from benign and malignant urothelial origin mimicking small in vitro tumors.

MATERIALS AND METHODS: Multicellular spheroids (MCS) were generated by "liquid-overlay" technique. Adhesion and penetration of viable FITC-labelled BCG into MCS from urothelial cancer cell lines and normal urothelial cells was studied by electron microscopy (TEM) and fluorescence microscopy. Spheroid growth during BCG-co-incubation was determined by light microscopy. Peripheral blood mononuclear cells (PBMC) were stimulated with BCG to generate BCG-activated-killer (BAK) cells. The infiltration of these effectors and of lymphokine-activated killer (LAK) cells into MCS was examined at different intervals by means of immunohistochemistry. The resulting cytotoxicity was judged in a 3H-l-methionine release assay.

RESULTS: BCG adhered to MCS from tumor cells but not to benign cell MCS. Intracellular internalization of the bacteria was detectable in superficial tumor cell-layers (1-5) whereas BCG was not found in deeper layers. Proliferation of malignant MCS was reduced in the presence of BCG. Benign MCS showed contact inhibition growth arrest, which was not altered by BCG. BAK and LAK effector cells both infiltrated tumor cell MCS as opposed to unstimulated PBMC. In contrast to LAK cells, BAK cells did not infiltrate into benign cell MCS and were not cytotoxic towards them.

CONCLUSION: With regard to the clinical situation the selective adhesion and internalization of BCG to malignant cells might explain why BCG has been rarely found in follow-up biopsies in tumor free patients. More interestingly, the selective adhesion of BCG to and infiltration of BAK effector cells into malignant cell spheroids suggests a selective mode of action of BCG.}, } @article {pmid10406840, year = {1999}, author = {Gagneux, P and Varki, A}, title = {Evolutionary considerations in relating oligosaccharide diversity to biological function.}, journal = {Glycobiology}, volume = {9}, number = {8}, pages = {747-755}, doi = {10.1093/glycob/9.8.747}, pmid = {10406840}, issn = {0959-6658}, mesh = {Animals ; *Biological Evolution ; Glycosylation ; Glycosyltransferases/metabolism ; Humans ; Oligosaccharides/chemistry/*classification/*metabolism ; Selection, Genetic ; }, abstract = {The oligosaccharide chains (glycans) attached to cell surface and extracellular proteins and lipids are known to mediate many important biological roles. However, for many glycans, there are still no evident functions that are of obvious benefit to the organism that synthesizes them. There is also no clear explanation for the extreme complexity and diversity of glycans that can be found on a given glycoconjugate or cell type. Based on the limited information available about the scope and distribution of this diversity among taxonomic groups, it is difficult to see clear trends or patterns consistent with different evolutionary lineages. It appears that closely related species may not necessarily share close similarities in their glycan diversity, and that more derived species may have simpler as well as more complex structures. Intraspecies diversity can also be quite extensive, often without obvious functional relevance. We suggest one general explanation for these observations, that glycan diversification in complex multicellular organisms is driven by evolutionary selection pressures of both endogenous and exogenous origin. We argue that exogenous selection pressures mediated by viral and microbial pathogens and parasites that recognize glycans have played a more prominent role, favoring intra- and interspecies diversity. This also makes it difficult to appreciate and elucidate the specific endogenous roles of the glycans within the organism that synthesizes them.}, } @article {pmid10403058, year = {1999}, author = {Soldati, T and Geissler, H and Schwarz, EC}, title = {How many is enough? Exploring the myosin repertoire in the model eukaryote Dictyostelium discoideum.}, journal = {Cell biochemistry and biophysics}, volume = {30}, number = {3}, pages = {389-411}, doi = {10.1007/BF02738121}, pmid = {10403058}, issn = {1085-9195}, mesh = {Actins/physiology ; Animals ; Cytoplasm/metabolism ; Cytoskeleton/physiology ; Dictyostelium/*metabolism ; Models, Biological ; Myosins/classification/*physiology ; Phagocytosis ; Phylogeny ; Protein Binding ; Signal Transduction ; Structure-Activity Relationship ; }, abstract = {The cytoplasm of eukaryotic cells is a very complex milieu and unraveling how its unique cytoarchitecture is achieved and maintained is a central theme in modern cell biology. It is crucial to understand how organelles and macro-complexes of RNA and/or proteins are transported to and/or maintained at their specific cellular locations. The importance of filamentous-actin-directed myosin-powered cargo transport was only recently realized, and after an initial explosion in the identification of new molecules, the field is now concentrating on their functional dissection. Direct connections of myosins to a variety of cellular tasks are now slowly emerging, such as in cytokinesis, phagocytosis, endocytosis, polarized secretion and exocytosis, axonal transport, etc. Unconventional myosins have been identified in a wide variety of organisms, making the presence of actin and myosins a hallmark of eukaryotism. The genome of S. cerevisiae encodes only five myosins, whereas a mammalian cell has the capacity to express between two and three dozen myosins. Why is it so crucial to arrive at this final census? The main questions that we would like to discuss are the following. How many distinct myosin-powered functions are carried out in a typical higher eukaryote? Or, in other words, what is the minimal set of myosins essential to accomplish the multitude of tasks related to motility and intracellular dynamics in a multicellular organism? And also, as a corollary, what is the degree of functional redundancy inside a given myosin class? In that respect, the choice of a model organism suitable for such an investigation is more crucial than ever. Here we argue that Dictyostelium discoideum is affirming its position as an ideal system of intermediate complexity to study myosin-powered trafficking and is or will soon become the second eukaryote for which complete knowledge of the whole repertoire of myosins is available.}, } @article {pmid10377580, year = {1999}, author = {Aleshin, VV and Vladychenskaia, NS and Kedrova, OS and Miliutina, IA and Petrov, NB}, title = {[Secondary structure of hairpin 17 of the lower multicellular animal Rhopalura ophiocomae (Mesozoa: Orthonectida) as an example of "punctuated equilibrium" in the evolution of 18S ribosomal RNA].}, journal = {Molekuliarnaia biologiia}, volume = {33}, number = {2}, pages = {319-329}, pmid = {10377580}, issn = {0026-8984}, mesh = {Animals ; Base Sequence ; *Evolution, Molecular ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Platyhelminths/*genetics ; RNA, Ribosomal, 18S/chemistry/*genetics ; }, } @article {pmid10376684, year = {1999}, author = {Françon, P and Maiorano, D and Méchali, M}, title = {Initiation of DNA replication in eukaryotes: questioning the origin.}, journal = {FEBS letters}, volume = {452}, number = {1-2}, pages = {87-91}, doi = {10.1016/s0014-5793(99)00585-2}, pmid = {10376684}, issn = {0014-5793}, mesh = {Animals ; DNA Replication/*physiology ; Eukaryotic Cells/metabolism/*physiology ; Humans ; Replication Origin/*physiology ; }, abstract = {Although proteins involved in DNA replication in yeast have counterparts in multicellular organisms, the definition of an origin of DNA replication and its control in higher eukaryotes might obey to different rules. Origins of DNA replication that are site-specific have been found, supporting the notion that specific DNA regions are used to initiate DNA synthesis along metazoan chromosomes. However, the notion that specific sequences will define origins is still being debated. The variety and complexity of transcriptional programs that have to be regulated in multicellular organisms may impose a plasticity that would not be compatible with a fixed origin simply defined at the sequence level. Such a plasticity would be essential to developmental programs where the control of DNA replication could be more integrated to the control of gene expression than in unicellular eukaryotes.}, } @article {pmid10361098, year = {1999}, author = {Copley, RR and Schultz, J and Ponting, CP and Bork, P}, title = {Protein families in multicellular organisms.}, journal = {Current opinion in structural biology}, volume = {9}, number = {3}, pages = {408-415}, doi = {10.1016/S0959-440X(99)80055-4}, pmid = {10361098}, issn = {0959-440X}, mesh = {Animals ; Conserved Sequence ; Genome ; Humans ; Intracellular Fluid/physiology ; *Multigene Family ; Phylogeny ; Proteins/*chemistry/*genetics/physiology ; Signal Transduction/genetics ; }, abstract = {The complete sequence of the nematode worm Caenorhabditis elegans contains the genetic machinery that is required to undertake the core biological processes of single cells. However, the genome also encodes proteins that are associated with multicellularity, as well as others that are lineage-specific expansions of phylogenetically widespread families and yet more that are absent in non-nematodes. Ongoing analysis is beginning to illuminate the similarities and differences among human proteins and proteins that are encoded by the genomes of the multicellular worm and the unicellular yeast, and will be essential in determining the reliability of transferring experimental data among phylogenetically distant species.}, } @article {pmid10360839, year = {1999}, author = {Mark, C and Abrink, M and Hellman, L}, title = {Comparative analysis of KRAB zinc finger proteins in rodents and man: evidence for several evolutionarily distinct subfamilies of KRAB zinc finger genes.}, journal = {DNA and cell biology}, volume = {18}, number = {5}, pages = {381-396}, doi = {10.1089/104454999315277}, pmid = {10360839}, issn = {1044-5498}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Northern ; Cloning, Molecular ; DNA, Complementary/analysis ; DNA-Binding Proteins/biosynthesis ; *Evolution, Molecular ; Humans ; Kruppel-Like Transcription Factors ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Sequence Analysis ; Sequence Homology, Amino Acid ; Zinc Fingers/*genetics ; }, abstract = {Although the KRAB zinc finger proteins probably constitute the single largest class of transcription factors within the human genome, almost nothing is known about their biological function. To increase our knowledge about this interesting and relatively unexplored family of potent transcriptional repressors, we here present the cloning, structural analysis, and expression study of three novel mouse KRAB zinc finger proteins. In addition, we present an extensive comparative analysis of various members of this gene family based on the structure of the common KRAB A motif. At least three larger subfamilies of KRAB zinc finger proteins are identified: one carrying the classical KRAB A motif only, another holding both a classical KRAB A and a classical KRAB B motif, and a third holding a classical KRAB A and a highly divergent KRAB B domain, named b. A large variation both in size and in primary amino acid sequence was observed in the linker region between the KRAB domain and the C-terminally located zinc finger repeats. This variability indicates that this region is of minor importance for the biological function of KRAB-containing zinc finger proteins. The fact that in many zinc finger genes, the entire or almost the entire linker region is composed of degenerate finger motifs substantiates this conclusion. The absence of identifiable KRAB A and B motifs in the genome of yeast, Saccharomyces cerevisiae, indicates a relatively late appearance of the KRAB domain in evolution and may suggest that the biological functions are restricted to multicellular organisms. In addition, we show that the expression of individual members of one subfamily of KRAB zinc finger genes is restricted to specific hematopoietic cell lineages. This finding suggests that KRAB zinc finger proteins may play a role in lineage commitment, possibly silencing leakage transcription from nonlineage-expressed genes.}, } @article {pmid10359696, year = {1999}, author = {Bement, WM and Mandato, CA and Kirsch, MN}, title = {Wound-induced assembly and closure of an actomyosin purse string in Xenopus oocytes.}, journal = {Current biology : CB}, volume = {9}, number = {11}, pages = {579-587}, doi = {10.1016/s0960-9822(99)80261-9}, pmid = {10359696}, issn = {0960-9822}, support = {GM52932-01A2/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/metabolism ; Actomyosin/*metabolism ; Animals ; Female ; GTP Phosphohydrolases/metabolism ; GTP-Binding Proteins/metabolism ; Microtubules/physiology ; Myosins/metabolism ; Oocytes/metabolism ; Wounds and Injuries/*metabolism ; Xenopus ; rho GTP-Binding Proteins ; }, abstract = {BACKGROUND: Both single cells and multicellular systems rapidly heal physical insults but are thought to do so by distinctly different mechanisms. Wounds in single cells heal by calcium-dependent membrane fusion, whereas multicellular wounds heal by a variety of different mechanisms, including circumferential contraction of an actomyosin 'purse string' that assembles around wound borders and is dependent upon the small GTPase Rho.

RESULTS: We investigated healing of puncture wounds made in Xenopus oocytes, a single-cell system. Oocyte wounds rapidly assumed a circular morphology and constricted circumferentially, coincident with the recruitment of filamentous actin (F-actin) and myosin-II to the wound borders. Surprisingly, recruitment of myosin-II to wound borders occurred before that of F-actin. Further, experimental disruption of F-actin prevented healing but did not prevent myosin-II recruitment. Actomyosin purse-string assembly and closure was dependent on Rho GTPases and extracellular calcium. Wounding resulted in reorganization of microtubules into an array similar to that which forms during cytokinesis in Xenopus embryos. Experimental perturbation of oocyte microtubules before wounding inhibited actomyosin recruitment and wound closure, whereas depolymerization of microtubules after wounding accelerated wound closure.

CONCLUSIONS: We conclude the following: actomyosin purse strings can close single-cell wounds; myosin-II is recruited to wound borders independently of F-actin; purse-string assembly is dependent on a Rho GTPase; and purse-string assembly and closure are controlled by microtubules. More generally, the results indicate that actomyosin purse strings have been co-opted through evolution to dispatch a broad variety of single-cell and multicellular processes, including wound healing, cytokinesis and morphogenesis.}, } @article {pmid10355371, year = {1999}, author = {Tempesti, G and Mange, D and Stauffer, A}, title = {The Embryonics Project: a machine made of artificial cells.}, journal = {Rivista di biologia}, volume = {92}, number = {1}, pages = {143-188}, pmid = {10355371}, issn = {0035-6050}, mesh = {Animals ; Biomedical Engineering ; Computer Simulation ; *Electronics, Medical ; *Embryology ; Female ; Genome ; Models, Structural ; Pregnancy ; Software Design ; *Stem Cells ; Systems Theory ; }, abstract = {It is possible to trace the origins of biological inspiration in the design of electronic circuits to the very dawn of the field of computer engineering, with the work of John von Neumann in the 1940s. To his brilliance we owe not only the first methodical attempts to define the electronic equivalents of many fundamental biological process, but also the development of the first self-replicating computing machines. Unfortunately, the electronic technology of the time would not allow a physical realization of von Neumann's machines, and it was not until the introduction of new programmable circuits in the 1980s that the field of bio-inspired machines gained new momentum. In this article, we describe the Embryonics (embryonic electronics) Project, an attempt to draw inspiration from the ontogenetic processes that determine the growth of multicellular organisms in the design of new, massively parallel arrays of processors (the artificial cells). Our cells are simple processors, all based on an identical hardware structure and all containing the same program (our artificial genome), but executing different parts of the genome depending on their spatial coordinates within the array. As in living beings, the presence of the genome in every cell allows the introduction of features such as self-replication and self-repair (cicatrization). In addition, the cells are implemented using an array of programmable elements (the artificial molecules), which allows their structure to be adapted to a given application. Through the parallel operation of many of these simple processors, we hope to realize highly complex systems, the equivalent of multicellular organisms in the natural world.}, } @article {pmid10343395, year = {1999}, author = {Burke, RD}, title = {Invertebrate integrins: structure, function, and evolution.}, journal = {International review of cytology}, volume = {191}, number = {}, pages = {257-284}, doi = {10.1016/s0074-7696(08)60161-8}, pmid = {10343395}, issn = {0074-7696}, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Integrins/*chemistry/physiology ; Invertebrates/*physiology ; Ligands ; Molecular Sequence Data ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid ; Structure-Activity Relationship ; }, abstract = {Integrins are a family of molecules that have fundamental roles in cell-cell and cell-matrix adhesion. It is thought that all metazoan cells have one or more integrin receptors on their surface and that these molecules may have been key in the evolution of multicellularity. Knowledge of the structure, function, and distribution of integrin subunits in invertebrate phyla remains incomplete. However, through the recent use of polymerase chain reaction, integrin subunits have been identified in at least five phyla; sponges, cnidarians, nemadodes, arthropods, and echinoderms. The structure of all of the invertebrate subunits is remarkably similar to that of vertebrate integrin subunits. Some experimental data and patterns of expression indicate that invertebrate integrins have a range of functions similar to those of vertebrate integrins. The ligands are not well characterized but at least two laminin-binding receptors have been identified and two other receptors appear to bind using Arg-Gly-Asp motifs. Invertebrate integrins are present during development, in adults, and on a range of cell types including cells with immunological functions such as hemocytes and coelomocytes. Analysis of the invertebrate beta subunits indicates that the invertebrate integrins have diverged independently within each phylum. The two major clades of vertebrate integrins (beta 1, beta 2, beta 7 and beta 3, beta 5, beta 6, beta 8) appear to have radiated since the divergence of the deuterostomes and there are no distinct orthologous subunits in any of the invertebrate phyla. Since fundamental functions of integrins appear to be conserved, studies of invertebrate integrins have the potential of contributing to our understanding of this important group of receptors.}, } @article {pmid10343281, year = {1999}, author = {Stoka, AM}, title = {Phylogeny and evolution of chemical communication: an endocrine approach.}, journal = {Journal of molecular endocrinology}, volume = {22}, number = {3}, pages = {207-225}, doi = {10.1677/jme.0.0220207}, pmid = {10343281}, issn = {0952-5041}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Biological Factors/chemistry/*physiology ; Endocrine Glands/*physiology ; Humans ; *Phylogeny ; }, abstract = {The present review assesses the phylogenetic history of information molecules (bioregulators pheromones, hormones, neuroactive compounds), receptors, transducers, second messengers) in uni- and multicellular organisms. Transitional stages between contemporary endocrine secretions including hormones and neuroactive materials, and primogenial exocrine compounds (pheromones) are proposed. Severalhypotheses have been developed to explain the origin and evolution of bioregulator/receptor units. Finally, how these primordial information molecules have either been co-opted or have changed their function during the course of biological evolution is analysed.}, } @article {pmid10229577, year = {1999}, author = {Honda, D and Yokota, A and Sugiyama, J}, title = {Detection of seven major evolutionary lineages in cyanobacteria based on the 16S rRNA gene sequence analysis with new sequences of five marine Synechococcus strains.}, journal = {Journal of molecular evolution}, volume = {48}, number = {6}, pages = {723-739}, doi = {10.1007/pl00006517}, pmid = {10229577}, issn = {0022-2844}, mesh = {*Biological Evolution ; Cyanobacteria/classification/*genetics ; Models, Genetic ; Molecular Sequence Data ; Oceans and Seas ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA ; Water Microbiology ; }, abstract = {Although molecular phylogenetic studies of cyanobacteria on the basis of the 16S rRNA gene sequence have been reported, the topologies were unstable, especially in the inner branchings. Our analysis of 16S rRNA gene phylogeny by the maximum-likelihood and neighbor-joining methods combined with rate homogeneous and heterogeneous models revealed seven major evolutionary lineages of the cyanobacteria, including prochlorophycean organisms. These seven lineages are always stable on any combination of these methods and models, fundamentally corresponding to phylogenetic relationships based on other genes, e.g., psbA, rbcL, rnpB, rpoC, and tufA. Moreover, although known genotypic and phenotypic characters sometimes appear paralleled in independent lineages, many characters are not contradictory within each group. Therefore we propose seven evolutionary groups as a working hypothesis for successive taxonomic reconstruction. New 16S rRNA sequences of five unicellular cyanobacterial strains, PCC 7001, PCC 7003, PCC 73109, PCC 7117, and PCC 7335 of Synechococcus sp., were determined in this study. Although all these strains have been assigned to "marine clusters B and C," they were separated into three lineages. This suggests that the organisms classified in the genus Synechococcus evolved diversely and should be reclassified in several independent taxonomic units. Moreover, Synechococcus strains and filamentous cyanobacteria make a monophyletic group supported by a comparatively high statistical confidence value (80 to 100%) in each of the two independent lineages; therefore, these monophylies probably reflect the convergent evolution of a multicellular organization.}, } @article {pmid10229569, year = {1999}, author = {Ono, K and Suga, H and Iwabe, N and Kuma, K and Miyata, T}, title = {Multiple protein tyrosine phosphatases in sponges and explosive gene duplication in the early evolution of animals before the parazoan-eumetazoan split.}, journal = {Journal of molecular evolution}, volume = {48}, number = {6}, pages = {654-662}, doi = {10.1007/pl00006509}, pmid = {10229569}, issn = {0022-2844}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Cloning, Molecular ; *Gene Duplication ; Molecular Sequence Data ; *Phylogeny ; Porifera/genetics ; Protein Tyrosine Phosphatases/*genetics ; Sequence Homology, Amino Acid ; Time Factors ; }, abstract = {Protein tyrosine phosphatases (PTPs) regulate various physiological events in animal cells. They comprise a diverse family which are classified into two categories, receptor type and nonreceptor type. From the domain organization and phylogenetic tree, we have classified known PTPs into 17 subtypes (9 receptor-type and 8 nonreceptor-type PTPs) which are characterized by different organization of functional domain and independent cluster in tree. The receptor type PTPs are thought to be implicated in cell-cell adhesion by association of cell adhesion molecules. Since sponges are the most primitive multicellular animals and are thought to be lacking cell cohesiveness and coordination typical of eumetazoans, cloning and sequencing of PTP cDNAs of Ephydatia fluviatilis (freshwater sponge) have been conducted by RT-PCR to determine whether or not sponges have PTP genes in their genomes. We have isolated nine PTPs, of which five are possibly receptor type. A phylogenetic tree including the sponge PTPs revealed that most of the gene duplications that gave rise to the 17 subtypes had been completed in the very early evolution of animals before the parazoan-eumetazoan split, the earliest branching among extant animal phyla. The family tree also revealed the rapid evolutionary rate of PTP subtypes in the early stage of animal evolution.}, } @article {pmid10229568, year = {1999}, author = {Suga, H and Koyanagi, M and Hoshiyama, D and Ono, K and Iwabe, N and Kuma, K and Miyata, T}, title = {Extensive gene duplication in the early evolution of animals before the parazoan-eumetazoan split demonstrated by G proteins and protein tyrosine kinases from sponge and hydra.}, journal = {Journal of molecular evolution}, volume = {48}, number = {6}, pages = {646-653}, doi = {10.1007/pl00006508}, pmid = {10229568}, issn = {0022-2844}, mesh = {Amino Acid Substitution ; Animals ; Evolution, Molecular ; Fungi/genetics ; GTP-Binding Proteins/*genetics ; *Gene Duplication ; Genetic Variation ; Humans ; Hydra/*genetics ; Molecular Sequence Data ; Phylogeny ; Plants/genetics ; Porifera/*genetics ; Protein-Tyrosine Kinases/*genetics ; }, abstract = {To know whether genes involved in cell-cell communication typical of multicellular animals dramatically increased in concert with the Cambrian explosion, the rapid evolutionary burst in the major groups of animals, and whether these genes exist in the sponge lacking cell cohesiveness and coordination typical of eumetazoans, we have carried out cloning of the G-protein alpha subunit (Galpha) and the protein tyrosine kinase (PTK) cDNAs from Ephydatia fluviatilis (freshwater sponge) and Hydra magnipapillata strain 105 (hydra). We obtained 13 Galpha and 20 PTK cDNAs. Generally animal gene families diverged first by gene duplication (subtype duplication) that gave rise to diverse subtypes with different primary functions, followed by further gene duplication in the same subtype (isoform duplication) that gave rise to isoform genes with virtually identical function. Phylogenetic trees of Galpha and PTK families including cDNAs from sponge and hydra revealed that most of the present-day subtypes had been established in the very early evolution of animals before the parazoan-eumetazoan split, the earliest branching among the extant animal phyla, by extensive subtype duplication: for PTK and Galpha families, 23 and 9 subtype duplications were observed in the early stage before the parazoan-eumetazoan split, respectively, and after that split, only 2 and 1 subtype duplications were found, respectively. After the separation from arthropods, vertebrates underwent frequent isoform duplications before the fish-tetrapod split. Furthermore, rapid amino acid changes appear to have occurred in concert with the extensive subtype duplication and isoform duplication. Thus the pattern of gene diversification during animal evolution might be characterized by bursts of gene duplication interrupted by considerably long periods of silence, instead of proceeding gradually, and there might be no direct link between the Cambrian explosion and the extensive gene duplication that generated diverse functions (subtypes) of these families.}, } @article {pmid10225436, year = {1999}, author = {Strasser, A}, title = {Dr. Josef Steiner Cancer Research Prize Lecture: the role of physiological cell death in neoplastic transformation and in anti-cancer therapy.}, journal = {International journal of cancer}, volume = {81}, number = {4}, pages = {505-511}, doi = {10.1002/(sici)1097-0215(19990517)81:4<505::aid-ijc1>3.0.co;2-j}, pmid = {10225436}, issn = {0020-7136}, mesh = {Animals ; Antineoplastic Agents/*therapeutic use ; Apoptosis ; Awards and Prizes ; Biological Evolution ; Cell Cycle/*physiology ; Cell Death/*physiology ; *Cell Transformation, Neoplastic ; Humans ; Medical Oncology ; Mice ; Mice, Transgenic ; Neoplasms/drug therapy/*genetics/pathology ; }, abstract = {Cell death is a physiological process which is required for normal development and existence of multi-cellular organisms. Physiological cell death, or apoptosis, is controlled by an evolutionarily conserved mechanism. Abnormalities in this process are implicated as a cause or contributing factor in a variety of diseases. Inhibition of apoptosis can promote neoplastic transformation, particularly in combination with dysregulated cell-cycle control, and can influence the response of tumour cells to anti-cancer therapy. Molecular biological and biochemical approaches are used to find missing cell-death regulators and to define signalling cascades, while experiments in genetically modified mice will identify the essential function of these molecules. Discoveries from cell death research should provide clues for designing therapies for a variety of diseases, including degenerative disorders, auto-immunity and cancer.}, } @article {pmid10222161, year = {1999}, author = {Lin, Q and Buckler, ES and Muse, SV and Walker, JC}, title = {Molecular evolution of type 1 serine/threonine protein phosphatases.}, journal = {Molecular phylogenetics and evolution}, volume = {12}, number = {1}, pages = {57-66}, doi = {10.1006/mpev.1998.0560}, pmid = {10222161}, issn = {1055-7903}, mesh = {Amino Acid Sequence ; Animals ; Arabidopsis/genetics ; Databases, Factual ; *Evolution, Molecular ; Genetic Variation ; Molecular Sequence Data ; Phosphoprotein Phosphatases/*genetics ; Phylogeny ; Rabbits ; Saccharomyces cerevisiae/genetics ; Sequence Homology, Amino Acid ; Trypanosoma brucei brucei/genetics ; }, abstract = {Type 1 serine/threonine protein phosphatases (PP1s) play key roles in many cellular processes. To understand the evolutionary relationships among PP1s from various kingdoms and to provide a valid basis to evaluate the structure-function relationships of these phosphatases, 44 PP1 sequences were aligned, revealing a high sequence similarity among PP1 homologs. About one-third of the total amino acids are conserved in all the sequences studied. Most of these conserved amino acids are located within a 270-amino-acid core region. They include most sites critical to the activity and regulation of PP1s based on three-dimensional structural studies of mammalian PP1s. Positional variation analysis using a sliding window approach revealed two variable blocks in the 270-amino-acid core region. The major variable block corresponds to a subdomain composed of three alpha-helices (alphaG, alphaH, and alphaI) and three beta-sheets (beta7, beta8, and beta9). Phylogenetic analyses suggested that plant and animal PP1s form distinct monophyletic groups. The plant PP1 family contains several subgroups that may be older than the monocot-dicot divergence. In the animal PP1 family, different vertebrate isoforms appear to form distinct subgroups. Relative substitution rate studies indicated that plant PP1s are more diverse than animal PP1s, with an average substitution rate 1.5 times as large as that of animal PP1s. The possible involvement of PP1s in the establishment of multicellularity is discussed.}, } @article {pmid10200288, year = {1999}, author = {Duret, L and Mouchiroud, D}, title = {Expression pattern and, surprisingly, gene length shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {96}, number = {8}, pages = {4482-4487}, pmid = {10200288}, issn = {0027-8424}, mesh = {Animals ; Arabidopsis/*genetics ; *Biological Evolution ; Caenorhabditis elegans/embryology/*genetics/growth & development ; Codon/*genetics ; Drosophila melanogaster/*genetics ; Expressed Sequence Tags ; *Gene Expression Regulation ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Mutation ; RNA, Messenger/analysis ; Selection, Genetic ; }, abstract = {We measured the expression pattern and analyzed codon usage in 8,133, 1,550, and 2,917 genes, respectively, from Caenorhabditis elegans, Drosophila melanogaster, and Arabidopsis thaliana. In those three species, we observed a clear correlation between codon usage and gene expression levels and showed that this correlation is not due to a mutational bias. This provides direct evidence for selection on silent sites in those three distantly related multicellular eukaryotes. Surprisingly, there is a strong negative correlation between codon usage and protein length. This effect is not due to a smaller size of highly expressed proteins. Thus, for a same-expression pattern, the selective pressure on codon usage appears to be lower in genes encoding long rather than short proteins. This puzzling observation is not predicted by any of the current models of selection on codon usage and thus raises the question of how translation efficiency affects fitness in multicellular organisms.}, } @article {pmid10191498, year = {1998}, author = {Hardingham, GE and Bading, H}, title = {Nuclear calcium: a key regulator of gene expression.}, journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}, volume = {11}, number = {4}, pages = {345-358}, doi = {10.1023/a:1009257909785}, pmid = {10191498}, issn = {0966-0844}, mesh = {Animals ; Calcium/*physiology ; Cell Nucleus/*metabolism ; Cyclic AMP Response Element-Binding Protein/metabolism ; *Gene Expression Regulation ; Humans ; Learning/physiology ; Mammals ; Memory/physiology ; Neurons/*physiology ; Phosphorylation ; *Signal Transduction ; Transcription, Genetic ; }, abstract = {Through the evolution of multicellular organisms, calcium has emerged as the preferred ion for intracellular signalling. It now occupies a pivotal role in many cell types and nowhere is it more important than in neurons, where it mediates both the relaying and long-term storage of information. The latter is a process that enables learning and memory to be formed and requires the activation of gene expression by calcium signals. Evidence from a number of diverse organisms shows that transcription mediated by the transcription factor CREB is critical for learning and memory. Here we review the features of CREB activation by calcium signals in mammalian cells. In contrast to other transcription factors, its regulation is dependent on an elevation of nuclear calcium concentration, potentially placing this spatially distinct pool of calcium as an important mediator of information storage.}, } @article {pmid10101604, year = {1998}, author = {Joulin, V}, title = {[Apoptosis and liver diseases].}, journal = {Comptes rendus des seances de la Societe de biologie et de ses filiales}, volume = {192}, number = {6}, pages = {1077-1094}, pmid = {10101604}, issn = {0037-9026}, mesh = {Animals ; *Apoptosis ; Autoimmune Diseases/pathology ; Biological Evolution ; Cell Division ; Communicable Diseases/pathology ; Homeostasis ; Humans ; Liver Diseases/*pathology/physiopathology ; Liver Neoplasms/pathology ; }, abstract = {Regulation of homeostasic balance between cell proliferation and cell death, called apoptosis, is essential for development and maintenance of multicellular organisms. Recent research into the molecular mechanisms of apoptosis has revealed that apoptosis is a genetically and evolutionarily conserved process that can become deranged when the components of the cellular apoptotic machinery are mutated, perturbated by viral gene products or present in inappropriated quantities. Analysis of the regulatory apoptotic pathways has led to a better understanding of the etiology and pathogenesis of many human diseases, notably cancers, infectious diseases or autoimmune diseases. Our understanding of the regulation of apoptosis in health and disease is far from complete and the use of understanding into new therapeutic modalities has only begun to be approached.}, } @article {pmid10099689, year = {1999}, author = {Feder, ME and Hofmann, GE}, title = {Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology.}, journal = {Annual review of physiology}, volume = {61}, number = {}, pages = {243-282}, doi = {10.1146/annurev.physiol.61.1.243}, pmid = {10099689}, issn = {0066-4278}, mesh = {Animals ; Biological Evolution ; Ecology ; Heat-Shock Proteins/genetics/*physiology ; Heat-Shock Response/physiology ; Humans ; Molecular Chaperones/*physiology ; Stress, Physiological/*physiopathology ; }, abstract = {Molecular chaperones, including the heat-shock proteins (Hsps), are a ubiquitous feature of cells in which these proteins cope with stress-induced denaturation of other proteins. Hsps have received the most attention in model organisms undergoing experimental stress in the laboratory, and the function of Hsps at the molecular and cellular level is becoming well understood in this context. A complementary focus is now emerging on the Hsps of both model and nonmodel organisms undergoing stress in nature, on the roles of Hsps in the stress physiology of whole multicellular eukaryotes and the tissues and organs they comprise, and on the ecological and evolutionary correlates of variation in Hsps and the genes that encode them. This focus discloses that (a) expression of Hsps can occur in nature, (b) all species have hsp genes but they vary in the patterns of their expression, (c) Hsp expression can be correlated with resistance to stress, and (d) species' thresholds for Hsp expression are correlated with levels of stress that they naturally undergo. These conclusions are now well established and may require little additional confirmation; many significant questions remain unanswered concerning both the mechanisms of Hsp-mediated stress tolerance at the organismal level and the evolutionary mechanisms that have diversified the hsp genes.}, } @article {pmid10092866, year = {1999}, author = {Bof, M and Brandolin, G and Satre, M and Klein, G}, title = {The mitochondrial adenine nucleotide translocator from Dictyostelium discoideum. Functional characterization and DNA sequencing.}, journal = {European journal of biochemistry}, volume = {259}, number = {3}, pages = {795-800}, doi = {10.1046/j.1432-1327.1999.00088.x}, pmid = {10092866}, issn = {0014-2956}, mesh = {Animals ; Atractyloside/analogs & derivatives/pharmacology ; Cell Differentiation/genetics ; Cell Division/drug effects ; Cloning, Molecular ; Dictyostelium/*genetics ; Enzyme Inhibitors/pharmacology ; Gene Expression Regulation, Developmental/genetics ; Mitochondria/*metabolism ; Mitochondrial ADP, ATP Translocases/chemistry/*genetics ; Phylogeny ; Protozoan Proteins/chemistry/*genetics ; RNA, Messenger/metabolism ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {The mitochondrial adenine nucleotide translocator (ANT) catalyses the exchange of ATP and ADP between the mitochondria and the cytosol. We have cloned and sequenced the gene encoding the Dictyostelium discoideum ANT (DdANT) and analysed its transcriptional regulation. The single copy D. discoideum ant gene encodes a protein of 309 amino acid residues with a predicted molecular mass of 33,469 Da and a pI of 9.85. These values are comparable to those of ANTs from mammals, insects and fungi. The long N-terminal extension characteristic of plant ANT is absent in DdANT. The protein coding region of the D. discoideum ant gene is interrupted by three introns. Polyclonal antibodies directed against the beef heart mitochondrial ANT or its C-terminal peptide recognized the D. discoideum protein. Northern blot analysis revealed that the expression of the D. discoideum ant gene decreased rapidly during the first hours of multicellular development but the amount of protein remained stable throughout differentiation.}, } @article {pmid10088145, year = {1999}, author = {Buznikov, GA and Shmukler YuB, and Lauder, JM}, title = {Changes in the physiological roles of neurotransmitters during individual development.}, journal = {Neuroscience and behavioral physiology}, volume = {29}, number = {1}, pages = {11-21}, pmid = {10088145}, issn = {0097-0549}, support = {HAD 22052/AD/ADAMHA HHS/United States ; }, mesh = {Aging/*physiology ; Animals ; Embryonic and Fetal Development/*physiology ; Female ; Growth/*physiology ; Humans ; Neurotransmitter Agents/*physiology ; Pregnancy ; }, abstract = {The classical neurotransmitters (acetylcholine and biogenic monoamines) are multifunctional substances involved in intra- and intercellular signaling at all stages of ontogenesis in multicellular animals. A cyclical scheme is proposed to describe age-related changes in neurotransmitter functions at different stages of development from oocyte maturation to neuron formation. This may reflect not only the temporospatial organization of neurotransmitter processes, but also the origin of the functions of acetylcholine and biogenic monoamines from the protosynapses of the cleaved embryo to neuronal synapses.}, } @article {pmid10073661, year = {1999}, author = {Kennel, SJ and Stabin, M and Roeske, JC and Foote, LJ and Lankford, PK and Terzaghi-Howe, M and Patterson, H and Barkenbus, J and Popp, DM and Boll, R and Mirzadeh, S}, title = {Radiotoxicity of bismuth-213 bound to membranes of monolayer and spheroid cultures of tumor cells.}, journal = {Radiation research}, volume = {151}, number = {3}, pages = {244-256}, pmid = {10073661}, issn = {0033-7587}, mesh = {Alpha Particles/therapeutic use ; Animals ; Antibodies, Monoclonal/metabolism/therapeutic use ; Bismuth/*therapeutic use ; Cell Death/radiation effects ; Cell Membrane/metabolism ; Immunoconjugates/metabolism/*therapeutic use ; Kinetics ; Mice ; Radioisotopes/*therapeutic use ; Radiotherapy Dosage ; Spheroids, Cellular/*radiation effects ; Tumor Cells, Cultured ; Tumor Stem Cell Assay ; }, abstract = {Monoclonal antibody 13A to murine CD44 was used to bind the alpha-particle emitter 213Bi to cell surfaces of cultured EMT-6 or Line 1 tumor cells. Data on kinetics and saturation of binding, cell shape and nuclear size were used to calculate the absorbed dose to the nuclei. Treatment of monolayer cells with [213Bi]MAb 13A produced a classical exponential survival curve with no apparent shoulder. Microdosimetry analyses indicated that 1.4-1.7 Gy produced a 37% surviving fraction (D0). Multicellular spheroids were shown to bind [213Bi]MAb 13A mainly on the outer cell layer. Relatively small amounts of activity added to the spheroids resulted in relatively large absorbed doses. The result was that 3-6-fold less added radioisotope was necessary to kill similar fractions of cells in spheroids than in monolayer cells. These data are consistent with the interpretation that the alpha particles from a single 213Bi atom bound to one cell can penetrate and kill adjacent cells. Flow cytometry was used to sort cells originating from the periphery or from the interior of spheroids. Cells from the outside of the [213Bi]MAb 13A exposed spheroids had a lower surviving fraction per administered activity than cells from the interior. Cells were killed efficiently in spheroids up to 20-30 cells in diameter. The data support the hypothesis that alpha-particle emitters should be very efficient at killing cells in micrometastases of solid tumors.}, } @article {pmid10070250, year = {1999}, author = {DePamphilis, ML}, title = {Replication origins in metazoan chromosomes: fact or fiction?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {21}, number = {1}, pages = {5-16}, doi = {10.1002/(SICI)1521-1878(199901)21:1<5::AID-BIES2>3.0.CO;2-6}, pmid = {10070250}, issn = {0265-9247}, mesh = {Animals ; *DNA Replication ; Eukaryota/*genetics ; Eukaryotic Cells/*physiology ; *Genome ; Replication Origin/*genetics ; }, abstract = {The process by which eukaryotic cells decide when and where to initiate DNA replication has been illuminated in yeast, where specific DNA sequences (replication origins) bind a unique group of proteins (origin recognition complex) next to an easily unwound DNA sequence at which replication can begin. The origin recognition complex provides a platform on which additional proteins assemble to form a pre-replication complex that can be activated at S-phase by specific protein kinases. Remarkably, multicellular eukaryotes, such as frogs, flies, and mammals (metazoa), have counterparts to these yeast proteins that are required for DNA replication. Therefore, one might expect metazoan chromosomes to contain specific replication origins as well, a hypothesis that has long been controversial. In fact, recent results strongly support the view that DNA replication origins in metazoan chromosomes consist of one or more high frequency initiation sites and perhaps several low frequency ones that together can appear as a nonspecific initiation zone. Specific replication origins are established during G1-phase of each cell cycle by multiple parameters that include nuclear structure, chromatin structure, DNA sequence, and perhaps DNA modification. Such complexity endows metazoa with the flexibility to change both the number and locations of replication origins in response to the demands of animal development.}, } @article {pmid10069816, year = {1999}, author = {Vernis, L and Chasles, M and Pasero, P and Lepingle, A and Gaillardin, C and Fournier, P}, title = {Short DNA fragments without sequence similarity are initiation sites for replication in the chromosome of the yeast Yarrowia lipolytica.}, journal = {Molecular biology of the cell}, volume = {10}, number = {3}, pages = {757-769}, pmid = {10069816}, issn = {1059-1524}, mesh = {Centromere/genetics ; *Chromosomes, Fungal ; Cloning, Molecular ; DNA Replication/*genetics ; DNA, Fungal/*genetics ; Plasmids/genetics ; *Replication Origin ; Saccharomycetales/*genetics ; Sequence Homology, Nucleic Acid ; }, abstract = {We have previously shown that both a centromere (CEN) and a replication origin are necessary for plasmid maintenance in the yeast Yarrowia lipolytica (). Because of this requirement, only a small number of centromere-proximal replication origins have been isolated from Yarrowia. We used a CEN-based plasmid to obtain noncentromeric origins, and several new fragments, some unique and some repetitive sequences, were isolated. Some of them were analyzed by two-dimensional gel electrophoresis and correspond to actual sites of initiation (ORI) on the chromosome. We observed that a 125-bp fragment is sufficient for a functional ORI on plasmid, and that chromosomal origins moved to ectopic sites on the chromosome continue to act as initiation sites. These Yarrowia origins share an 8-bp motif, which is not essential for origin function on plasmids. The Yarrowia origins do not display any obvious common structural features, like bent DNA or DNA unwinding elements, generally present at or near eukaryotic replication origins. Y. lipolytica origins thus share features of those in the unicellular Saccharomyces cerevisiae and in multicellular eukaryotes: they are discrete and short genetic elements without sequence similarity.}, } @article {pmid10049920, year = {1999}, author = {Kusano, K and Berres, ME and Engels, WR}, title = {Evolution of the RECQ family of helicases: A drosophila homolog, Dmblm, is similar to the human bloom syndrome gene.}, journal = {Genetics}, volume = {151}, number = {3}, pages = {1027-1039}, pmid = {10049920}, issn = {0016-6731}, support = {GM-30948/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/*genetics ; Amino Acid Sequence ; Animals ; Bloom Syndrome/genetics ; Cell Survival ; Cloning, Molecular ; DNA Helicases/chemistry/*genetics ; Drosophila melanogaster/*genetics ; *Evolution, Molecular ; Humans ; Insect Proteins/genetics ; Models, Biological ; Models, Genetic ; Molecular Sequence Data ; Phylogeny ; Plasmids/genetics ; Polymerase Chain Reaction ; RecQ Helicases ; Sequence Alignment ; Suppression, Genetic ; }, abstract = {Several eukaryotic homologs of the Escherichia coli RecQ DNA helicase have been found. These include the human BLM gene, whose mutation results in Bloom syndrome, and the human WRN gene, whose mutation leads to Werner syndrome resembling premature aging. We cloned a Drosophila melanogaster homolog of the RECQ helicase family, Dmblm (Drosophila melanogaster Bloom), which encodes a putative 1487-amino-acid protein. Phylogenetic and dot plot analyses for the RECQ family, including 10 eukaryotic and 3 prokaryotic genes, indicate Dmblm is most closely related to the Homo sapiens BLM gene, suggesting functional similarity. Also, we found that Dmblm cDNA partially rescued the sensitivity to methyl methanesulfonate of Saccharomyces cerevisiae sgs1 mutant, demonstrating the presence of a functional similarity between Dmblm and SGS1. Our analyses identify four possible subfamilies in the RECQ family: (1) the BLM subgroup (H. sapiens Bloom, D. melanogaster Dmblm, and Caenorhabditis elegans T04A11.6); (2) the yeast RECQ subgroup (S. cerevisiae SGS1 and Schizosaccharomyces pombe rqh1/rad12); (3) the RECQL/Q1 subgroup (H. sapiens RECQL/Q1 and C. elegans K02F3.1); and (4) the WRN subgroup (H. sapiens Werner and C. elegans F18C5.2). This result may indicate that metazoans hold at least three RECQ genes, each of which may have a different function, and that multiple RECQ genes diverged with the generation of multicellular organisms. We propose that invertebrates such as nematodes and insects are useful as model systems of human genetic diseases.}, } @article {pmid9990861, year = {1998}, author = {Girault, JA and Labesse, G and Mornon, JP and Callebaut, I}, title = {Janus kinases and focal adhesion kinases play in the 4.1 band: a superfamily of band 4.1 domains important for cell structure and signal transduction.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {4}, number = {12}, pages = {751-769}, pmid = {9990861}, issn = {1076-1551}, mesh = {Amino Acid Sequence ; Animals ; Cell Adhesion Molecules/*chemistry/genetics/*metabolism ; Cytoskeletal Proteins/chemistry ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; Humans ; Membrane Proteins/*chemistry ; Molecular Sequence Data ; *Neuropeptides ; Phylogeny ; Protein-Tyrosine Kinases/*chemistry/genetics/*metabolism ; *Signal Transduction ; }, abstract = {The band 4.1 domain was first identified in the red blood cell protein band 4.1, and subsequently in ezrin, radixin, and moesin (ERM proteins) and other proteins, including tumor suppressor merlin/schwannomin, talin, unconventional myosins VIIa and X, and protein tyrosine phosphatases. Recently, the presence of a structurally related domain has been demonstrated in the N-terminal region of two groups of tyrosine kinases: the focal adhesion kinases (FAK) and the Janus kinases (JAK). Additional proteins containing the 4.1/JEF (JAK, ERM, FAK) domain include plant kinesin-like calmodulin-binding proteins (KCBP) and a number of uncharacterized open reading frames identified by systematic DNA sequencing. Phylogenetic analysis of amino acid sequences suggests that band 4.1/JEF domains can be grouped in several families that have probably diverged early during evolution. Hydrophobic cluster analysis indicates that the band 4.1/JEF domains might consist of a duplicated module of approximately 140 residues and a central hinge region. A conserved property of the domain is its capacity to bind to the membrane-proximal region of the C-terminal cytoplasmic tail of proteins with a single transmembrane segment. Many proteins with band 4.1/JEF domains undergo regulated intra- or intermolecular homotypic interactions. Additional properties common to band 4.1/JEF domains of several proteins are binding of phosphoinositides and regulation by GTPases of the Rho family. Many proteins with band 4. 1/JEF domains are associated with the actin-based cytoskeleton and are enriched at points of contact with other cells or the extracellular matrix, from which they can exert control over cell growth. Thus, proteins with band 4.1/JEF domain are at the crossroads between cytoskeletal organization and signal transduction in multicellular organisms. Their importance is underlined by the variety of diseases that can result from their mutations.}, } @article {pmid9949831, year = {1998}, author = {Green, DR and Amarante-Mendes, GP}, title = {The point of no return: mitochondria, caspases, and the commitment to cell death.}, journal = {Results and problems in cell differentiation}, volume = {24}, number = {}, pages = {45-61}, doi = {10.1007/978-3-540-69185-3_3}, pmid = {9949831}, issn = {0080-1844}, mesh = {Animals ; *Apoptosis/genetics ; *Caspases ; Humans ; *Mitochondria ; Models, Biological ; Oncogenes ; }, abstract = {Apoptosis is a specialized mode of cell death finely regulated at the molecular level and conserved throughout evolution. In many instances during normal development or in order to maintain the homeostasis of a multicellular organism, a strategic intracellular program is initiated ensuring the fate of unwanted cells. Interference with this program has been implicated in many pathologies, particularly in cancer and autoimmune diseases. What is most important, from the organism's point of view, is that the dismissal of the outcast cells is accomplished serenely, i.e., the dying cells resign their existence without causing an inflammatory reaction. Therefore, the ability to manipulate the cell death machinery is an obvious goal of medical research. Here, we debate the idea of the point-of-no-return and propose models for the role of "initiator" and "executioner" caspases in the death program. We argue that, in many circumstances, the cells are committed to die before the execution phase of apoptosis starts. This commitment event is coordinated by the mitochondria and can be blocked by anti-apoptotic oncogenes.}, } @article {pmid9933610, year = {1999}, author = {Hurst, ST and Rivier, DH}, title = {Identification of a compound origin of replication at the HMR-E locus in Saccharomyces cerevisiae.}, journal = {The Journal of biological chemistry}, volume = {274}, number = {7}, pages = {4155-4159}, doi = {10.1074/jbc.274.7.4155}, pmid = {9933610}, issn = {0021-9258}, support = {5T32-GM07283/GM/NIGMS NIH HHS/United States ; GM52103/GM/NIGMS NIH HHS/United States ; }, mesh = {Chromosome Mapping ; *DNA Replication ; DNA, Fungal/biosynthesis ; *Gene Expression Regulation, Fungal ; Genes, Fungal ; Molecular Sequence Data ; Mutagenesis ; Nucleic Acid Hybridization ; *Regulatory Sequences, Nucleic Acid ; *Replication Origin ; Saccharomyces cerevisiae/*genetics ; }, abstract = {Eukaryotic chromosomal origins of replication are best defined in Saccharomyces cerevisiae. Previous analysis of yeast origins suggests that they are relatively simple structures comprised of three or four small DNA sequence elements contained within approximately 100-200-base pair regions (Gilbert, D. M. (1998) Curr. Opin. Genet. Dev. 8, 194-199). In contrast, the sequence elements that may comprise origins in multicellular eukaryotes are largely unknown. The yeast HMR-E region is both a chromosomal origin of replication and a silencer that represses transcription of adjacent genes through a position effect. The analysis presented here indicated that HMR-E had a novel DNA structure that was more complex than defined for other yeast origins, and thus revealed that there is variation in the structural complexity of yeast origins. In contrast to "simple" yeast origins, the origin at HMR-E consisted of at least three independent subregions that had the capacity to initiate replication. We have termed HMR-E a compound origin to reflect its structural complexity. Furthermore, only one origin within the compound origin was a silencer.}, } @article {pmid9929389, year = {1999}, author = {Sorhannus, U and Fox, M}, title = {Synonymous and nonsynonymous substitution rates in diatoms: a comparison between chloroplast and nuclear genes.}, journal = {Journal of molecular evolution}, volume = {48}, number = {2}, pages = {209-212}, doi = {10.1007/pl00006459}, pmid = {9929389}, issn = {0022-2844}, mesh = {Cell Nucleus/*metabolism ; Chloroplasts/*metabolism ; DNA, Plant/genetics ; Diatoms/classification/*genetics ; Evolution, Molecular ; *Genes, Plant ; }, abstract = {Rates of synonymous and nonsynonymous nucleotide substitutions and codon usage bias (ENC) were estimated for a number of nuclear and chloroplast genes in a sample of centric and pennate diatoms. The results suggest that DNA evolution has taken place, on an average, at a slower rate in the chloroplast genes than in the nuclear genes: a rate variation pattern similar to that observed in land plants. Synonymous substitution rates in the chloroplast genes show a negative association with the degree of codon usage bias, suggesting that genes with a higher degree of codon usage bias have evolved at a slower rate. While this relationship has been shown in both prokaryotes and multicellular eukaryotes, it has not been demonstrated before in diatoms.}, } @article {pmid9880549, year = {1999}, author = {Hallmann, A}, title = {Enzymes in the extracellular matrix of Volvox: an inducible, calcium-dependent phosphatase with a modular composition.}, journal = {The Journal of biological chemistry}, volume = {274}, number = {3}, pages = {1691-1697}, doi = {10.1074/jbc.274.3.1691}, pmid = {9880549}, issn = {0021-9258}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Western ; Calcium/*metabolism ; Chlorophyta/*enzymology ; Enzyme Induction ; Enzyme Inhibitors/pharmacology ; Extracellular Matrix/*enzymology ; Glycosylation ; Molecular Sequence Data ; Organophosphorus Compounds/metabolism ; Phosphoric Monoester Hydrolases/*biosynthesis/chemistry/*genetics/isolation & purification/*metabolism ; Protein Conformation ; Rabbits ; Substrate Specificity ; }, abstract = {The volvocine algae provide the unique opportunity for exploring development of an extracellular matrix. Volvox is the most advanced member of this family and represents the simplest multicellular organism, with differentiated cells, a complete division of labor, and a complex extracellular matrix, which serves structural and enzymatic functions. In Volvox carteri a glycosylated extracellular phosphatase was identified, which is partially released from the extracellular matrix into the growth medium. The phosphatase is synthesized in response to inorganic phosphate starvation and is strictly calcium-dependent. The metalloenzyme has been purified to homogeneity and characterized. Its gene and cDNA have been cloned. Comparisons of genomic and cDNA sequences revealed an extremely intron-rich gene (32 introns). With an apparent molecular mass of 160 kDa the Volvox extracellular phosphatase is the largest phosphatase cloned, with no sequence similarity to any other phosphatase. This enzyme exhibits a modular composition. There are two large domains and a small one. The large domains are highly homologous to each other and therefore most likely originated from gene duplication and fusion. At least one EF-hand motif for calcium binding was identified in this extracellular protein. Volvox extracellular phosphatase is the first calcium-dependent extracellular phosphatase to be cloned.}, } @article {pmid9874788, year = {1999}, author = {Gilland, E and Miller, AL and Karplus, E and Baker, R and Webb, SE}, title = {Imaging of multicellular large-scale rhythmic calcium waves during zebrafish gastrulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {96}, number = {1}, pages = {157-161}, pmid = {9874788}, issn = {0027-8424}, support = {R01 EY002007/EY/NEI NIH HHS/United States ; EY02007/EY/NEI NIH HHS/United States ; RR10291/RR/NCRR NIH HHS/United States ; }, mesh = {Aequorin ; Animals ; *Calcium Signaling ; *Gastrula ; Image Processing, Computer-Assisted ; Microscopy, Fluorescence/methods ; Morphogenesis ; *Periodicity ; Photons ; Somites ; Zebrafish/*embryology ; }, abstract = {Oscillations of cytosolic free calcium levels have been shown to influence gene regulation and cell differentiation in a variety of model systems. Intercellular calcium waves thus present a plausible mechanism for coordinating cellular processes during embryogenesis. Herein we report use of aequorin and a photon imaging microscope to directly observe a rhythmic series of intercellular calcium waves that circumnavigate zebrafish embryos over a 10-h period during gastrulation and axial segmentation. These waves first appeared at about 65% epiboly and continued to arise every 5-10 min up to at least the 16-somite stage. The waves originated from loci of high calcium activity bordering the blastoderm margin. Several initiating loci were active early in the wave series, whereas later a dorsal marginal midline locus predominated. On completion of epiboly, the dorsal locus was incorporated into the developing tail bud and continued to generate calcium waves. The locations and timing at which calcium dynamics are most active appear to correspond closely to embryonic cellular and syncytial sites of known morphogenetic importance. The observations suggest that a panembryonic calcium signaling system operating in a clock-like fashion might play a role during vertebrate axial patterning.}, } @article {pmid9873943, year = {1998}, author = {Sinkovics, J and Horvath, J and Horak, A}, title = {The origin and evolution of viruses (a review).}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {45}, number = {3-4}, pages = {349-390}, pmid = {9873943}, issn = {1217-8950}, mesh = {Animals ; *Biological Evolution ; Humans ; *Viruses ; }, abstract = {Viroids and prions might have existed early at the border of inanimate and living worlds. Most extant viruses can be characterized as derivatives of ancestors originating from episomal elements of prokaryotes (DNA phages) and later from eukaryotes. Retroviruses very likely originated from cellular retrotransposons. Retrograde evolution of some large viruses from obligatory intracellular bacteria is possible but the ontogenesis of extant bacteria does not include a viral form of existence (the filterable L forms are not viruses) and well-defined viruses do not regenerate back into vegetative bacterial forms. Biologists experimenting with the evolution of prokaryotic and eukaryotic ancient cells cannot ignore the earliest appearance of viruses within or outside the living matter. Viruses participated in and gave direction to the evolution and natural selection by coexisting with uni- and multicellular organisms for billions of years. The coevolution of viruses and their host cells is characterized by incessant attacks and counterattacks through gene rearrangements and mutations (induced in the virus by an immunological counterattack of the host or by transgression of species barriers by the virus) and recombinations. Recombinations occurred between viral and viral or viral and host genes. Acts of "molecular piracy" as practiced by ancient viruses endowed the virus with the expression of several host genes for the advantage of the virus in its replicative cycle and host-to-host spread. Probably the first immortalized and malignantly transformed cells were induced by viruses as viruses evolved anti-apoptotic measures. While infected cells resort to apoptotic death before the assembly of a new viral progeny, prominent are the anti-apoptotic measures viruses evolved in order to assure the completion of their full replicative cycle. Further, viruses may escape neutralization by host antibodies and may survive a counterattack by the host's T cells directed at virally infected cells of its own. Viruses may induce a form of tolerance and coexist with their host without inducing disease. Persistent and apparently or deceivingly apathogenic or even attenuated viral "quasi-species" populations may contain individual particles that regain virulence due to recombinations and/or gene rearrangements, especially when transgressing species barriers. Xenotropic viruses of animals may replicate in human cells and vice versa confounding experiments with xenotransplants or with use of veterinary viral vaccines for the treatment of human diseases.}, } @article {pmid9867504, year = {1998}, author = {Blackburn, DG}, title = {Structure, function, and evolution of the oviducts of squamate reptiles, with special reference to viviparity and placentation.}, journal = {The Journal of experimental zoology}, volume = {282}, number = {4-5}, pages = {560-617}, pmid = {9867504}, issn = {0022-104X}, mesh = {Animals ; *Biological Evolution ; Cloaca/anatomy & histology ; Female ; Lizards/*anatomy & histology/physiology ; Oviducts/*anatomy & histology/blood supply/physiology ; Placenta/*anatomy & histology/physiology ; Snakes/*anatomy & histology/physiology ; Uterus/anatomy & histology ; }, abstract = {In lizards and snakes, the oviducts function in fertilization, sperm storage, egg transport, eggshell deposition, maintenance of the early embryo, and expulsion of the egg or fetus. In viviparous forms they also contribute to placentae responsible for gas exchange and nutrient provision to the fetus. Dissections of species of 30 genera coupled with data from the literature indicate that squamate oviducts vary interspecifically in seven macroscopic features, including the extent and nature of regional differentiation, vascular supply, topographic asymmetry, number of oviducts, vaginal pouches, and relationship to the cloaca. The uterus, infundibulum, and vagina differ histologically in their epithelia, glands, and myometrial layers. Season cyclicity occurs in all three oviductal regions, most prominently in the uterus, and is under endocrinological control. Regional and cytological specializations reflect the diverse functions performed by the oviduct. Definitive evidence for oviductal albumen production and egg resorption is lacking. In viviparous squamates, three uterine specializations may facilitate maternal-fetal gas exchange: an attenuated epithelium, reduced uterine glands (and a reduced shell membrane), and increased vascularization. Contrary to previous reports, pregnant uteri show no epithelial erosion or capillary exposure. Specializations for nutrient provision to the fetus include mucosal hypertrophy, enlarged glandular epithelia, and multicellular glands whose secretions are absorbed by the chorioallantois. Comparisons with other amniotes indicate that squamates inherited the oviduct as an organ with capabilities for egg uptake and transport, fertilization, eggshell deposition, and oviposition. Other features have evolved convergently among squamates: infundibular sperm receptacles, unilateral oviduct loss, uterine gestation, placentation, and specializations for placentotrophy. Cladistic analysis indicates that oviductal features associated with deposition of tertiary egg investments in reptiles reflect evolutionary convergence as well as secondary simplification, rather than a unidirectional trend towards increased specialization.}, } @article {pmid9852331, year = {1999}, author = {Yamamoto, Y and Imaeda, K and Suzuki, H}, title = {Endothelium-dependent hyperpolarization and intercellular electrical coupling in guinea-pig mesenteric arterioles.}, journal = {The Journal of physiology}, volume = {514 (Pt 2)}, number = {Pt 2}, pages = {505-513}, pmid = {9852331}, issn = {0022-3751}, mesh = {Acetylcholine/pharmacology ; Animals ; Arterioles/drug effects/*physiology ; Charybdotoxin/pharmacology ; Endothelium, Vascular/drug effects/*physiology ; Gap Junctions/drug effects/physiology ; Glycyrrhetinic Acid/pharmacology ; Guinea Pigs ; Ileum/innervation ; In Vitro Techniques ; Male ; Membrane Potentials/drug effects/physiology ; Muscle, Smooth/innervation ; Muscle, Smooth, Vascular/drug effects/*physiology ; Patch-Clamp Techniques ; Splanchnic Circulation/*physiology ; }, abstract = {1. Using the conventional whole-cell clamp method, the electrical responses of individual smooth muscle and endothelial cells to acetylcholine (ACh) were observed in multicellular preparations where the two types of cells remained in close apposition. 2. In both types of cells, ACh induced similar hyperpolarizing responses which, when recorded in current clamp mode, had two phases (an initial fast and a second slower phase). 3. After blocking gap junctions, including myoendothelial junctions, with 18beta-glycyrrhetinic acid, ACh induced an outward current with two phases in voltage-clamped endothelial cells. The outward current appeared around -90 mV and increased linearly with the membrane depolarization. 4. In smooth muscle cells, ACh failed to induce a membrane current after gap junctions had been blocked with 18beta-glycyrrhetinic acid. The inhibition of ACh-induced response by 18beta-glycyrrhetinic acid was observed using either sharp or patch electrodes. 5. Nominally Ca2+-free solution reduced the initial phase and abolished the second phase of ACh-induced responses of endothelial cells. Both phases were also reduced by charybdotoxin (CTX). 6. Our results indicate that in guinea-pig mesenteric arterioles, ACh hyperpolarizes endothelial cells by activating Ca2+-activated K+ channels which are sensitive to CTX. On the other hand, hyperpolarizing responses detected in smooth muscle cells seem to originate in endothelial cells and conduct to the muscle layer via myoendothelial gap junctions.}, } @article {pmid9851918, year = {1998}, author = {Chervitz, SA and Aravind, L and Sherlock, G and Ball, CA and Koonin, EV and Dwight, SS and Harris, MA and Dolinski, K and Mohr, S and Smith, T and Weng, S and Cherry, JM and Botstein, D}, title = {Comparison of the complete protein sets of worm and yeast: orthology and divergence.}, journal = {Science (New York, N.Y.)}, volume = {282}, number = {5396}, pages = {2022-2028}, pmid = {9851918}, issn = {0036-8075}, support = {P41 HG001315/HG/NHGRI NIH HHS/United States ; P41 HG001315-16/HG/NHGRI NIH HHS/United States ; HG 00044/HG/NHGRI NIH HHS/United States ; HG01315/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*chemistry/genetics/physiology ; Evolution, Molecular ; Fungal Proteins/*chemistry/genetics/physiology ; Gene Expression Regulation ; Genes, Fungal ; Genes, Helminth ; Helminth Proteins/*chemistry/genetics/physiology ; Saccharomyces cerevisiae/*chemistry/genetics/physiology ; Sequence Homology, Amino Acid ; Signal Transduction ; }, abstract = {Comparative analysis of predicted protein sequences encoded by the genomes of Caenorhabditis elegans and Saccharomyces cerevisiae suggests that most of the core biological functions are carried out by orthologous proteins (proteins of different species that can be traced back to a common ancestor) that occur in comparable numbers. The specialized processes of signal transduction and regulatory control that are unique to the multicellular worm appear to use novel proteins, many of which re-use conserved domains. Major expansion of the number of some of these domains seen in the worm may have contributed to the advent of multicellularity. The proteins conserved in yeast and worm are likely to have orthologs throughout eukaryotes; in contrast, the proteins unique to the worm may well define metazoans.}, } @article {pmid9839617, year = {1998}, author = {Hamilton, G}, title = {Multicellular spheroids as an in vitro tumor model.}, journal = {Cancer letters}, volume = {131}, number = {1}, pages = {29-34}, doi = {10.1016/s0304-3835(98)00198-0}, pmid = {9839617}, issn = {0304-3835}, mesh = {Animals ; Cell Adhesion Molecules/physiology ; Drug Resistance, Neoplasm ; Extracellular Matrix/pathology ; Humans ; In Vitro Techniques ; *Models, Biological ; Neoplasm Metastasis ; Neoplasms, Experimental/*pathology ; Neovascularization, Pathologic ; Spheroids, Cellular/*pathology ; }, abstract = {Multicellular spheroids (MCS) have been used as an in vitro model system of micrometastases and avascular tumor regions for studying cell adhesion-dependent resistance to cytotoxic drugs and possible reversal by chemosensitizers and adhesion-reversing agents. Multicellular drug resistance has been linked to limited accessibility of cell subpopulations, active drug efflux, quiescence of cells in deeper layers due to cell contact inhibition and adverse microenvironmental conditions like acidic extracellular pH, hypoxia and nutritional depletion. The shortcomings of MCS as a tumor model include limited knowledge of the mechanisms leading to necrosis/apoptosis of core cells, the production of an extracellular matrix (ECM) by tumor cells instead of intratumoral normal cell populations and the complex relationship of MCS parameters like size, growth regulation, synthesis of ECM components and others on the origin and pretreatment of the tumor cells and specific culture conditions.}, } @article {pmid9818725, year = {1998}, author = {Rayner, TF and Stark, MJ}, title = {Identification and characterization of the KlCMD1 gene encoding Kluyveromyces lactis calmodulin.}, journal = {Yeast (Chichester, England)}, volume = {14}, number = {9}, pages = {869-875}, doi = {10.1002/(SICI)1097-0061(19980630)14:9<869::AID-YEA278>3.0.CO;2-U}, pmid = {9818725}, issn = {0749-503X}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Sequence ; Base Sequence ; Calmodulin/chemistry/*genetics ; Genes, Fungal ; Humans ; Kluyveromyces/*genetics ; Molecular Sequence Data ; Phylogeny ; Saccharomyces cerevisiae/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {The KlCMD1 gene was isolated from a Kluyveromyces lactis genomic library as a suppressor of the Saccharomyces cerevisiae temperature-sensitive mutant spc110-124, an allele previously shown to be suppressed by elevated copy number of the S. cerevisiae calmodulin gene CMD1. The KlCMD1 gene encodes a polypeptide which is 95% identical to S. cerevisiae calmodulin and 55% identical to calmodulin from Schizosaccharomyces pombe. Complementation of a S. cerevisiae cdm1 deletion mutant by KlCMD1 demonstrates that this gene encodes a functional calmodulin homologue. Multiple sequence alignment of calmodulins from yeast and multicellular eukaryotes shows that the K. lactis and S. cerevisiae calmodulins are considerably more closely related to each other than to other calmodulins, most of which have four functional Ca2+-binding EF hand domains. Thus like its S. cerevisiae counterpart Cmd1p, the KlCMD1 product is predicted to form only three Ca2+-binding motifs.}, } @article {pmid9811868, year = {1998}, author = {Shamblott, MJ and Axelman, J and Wang, S and Bugg, EM and Littlefield, JW and Donovan, PJ and Blumenthal, PD and Huggins, GR and Gearhart, JD}, title = {Derivation of pluripotent stem cells from cultured human primordial germ cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {95}, number = {23}, pages = {13726-13731}, pmid = {9811868}, issn = {0027-8424}, mesh = {Animals ; Biomarkers ; Cell Differentiation ; Cells, Cultured ; Germ Cells/*cytology ; Humans ; Immunophenotyping ; Karyotyping ; Mice ; Stem Cells/*cytology ; }, abstract = {Human pluripotent stem cells would be invaluable for in vitro studies of aspects of human embryogenesis. With the goal of establishing pluripotent stem cell lines, gonadal ridges and mesenteries containing primordial germ cells (PGCs, 5-9 weeks postfertilization) were cultured on mouse STO fibroblast feeder layers in the presence of human recombinant leukemia inhibitory factor, human recombinant basic fibroblast growth factor, and forskolin. Initially, single PGCs in culture were visualized by alkaline phosphatase activity staining. Over a period of 7-21 days, PGCs gave rise to large multicellular colonies resembling those of mouse pluripotent stem cells termed embryonic stem and embryonic germ (EG) cells. Throughout the culture period most cells within the colonies continued to be alkaline phosphatase-positive and tested positive against a panel of five immunological markers (SSEA-1, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81) that have been used routinely to characterize embryonic stem and EG cells. The cultured cells have been continuously passaged and found to be karyotypically normal and stable. Both XX and XY cell cultures have been obtained. Immunohistochemical analysis of embryoid bodies collected from these cultures revealed a wide variety of differentiated cell types, including derivatives of all three embryonic germ layers. Based on their origin and demonstrated properties, these human PGC-derived cultures meet the criteria for pluripotent stem cells and most closely resemble EG cells.}, } @article {pmid9798276, year = {1998}, author = {Furusawa, C and Kaneko, K}, title = {Emergence of multicellular organisms with dynamic differentiation and spatial pattern.}, journal = {Artificial life}, volume = {4}, number = {1}, pages = {79-93}, doi = {10.1162/106454698568459}, pmid = {9798276}, issn = {1064-5462}, mesh = {Animals ; Biological Evolution ; Body Patterning ; *Cell Adhesion ; *Cell Communication ; Cell Differentiation ; Cell Division ; Computational Biology ; Computer Simulation ; Diffusion ; Humans ; *Models, Biological ; }, abstract = {The origin of multicellular organisms and the mechanism of development in cell societies are studied by choosing a model with intracellular biochemical dynamics allowing for oscillations, cell-cell interaction through diffusive chemicals on a two-dimensional grid, and state-dependent cell adhesion. Cells differentiate due to a dynamical instability, as described by our "isologous diversification" theory. A fixed spatial pattern of differentiated cells emerges, where spatial information is sustained by cell-cell interactions. This pattern is robust against perturbations. With an adequate cell adhesion force, active cells are release that form the seed of a new generation of multicellular organisms, accompanied by death of the original multicellular unit as a halting state. It is shown that the emergence of multicellular organisms with differentiation, regulation, and life cycle is not an accidental event, but a natural consequence in a system of replicating cells with growth.}, } @article {pmid9797404, year = {1998}, author = {Bhattacharya, D and Weber, K and An, SS and Berning-Koch, W}, title = {Actin phylogeny identifies Mesostigma viride as a flagellate ancestor of the land plants.}, journal = {Journal of molecular evolution}, volume = {47}, number = {5}, pages = {544-550}, doi = {10.1007/pl00006410}, pmid = {9797404}, issn = {0022-2844}, mesh = {Actins/*genetics ; Base Sequence ; Chlorophyta/*genetics ; DNA Primers ; DNA, Complementary ; Molecular Sequence Data ; *Phylogeny ; }, abstract = {Green algae and land plants trace their evolutionary history to a unique common ancestor. This "green lineage" is phylogenetically subdivided into two distinct assemblages, the Chlorophyta and the Streptophyta. The Chlorophyta includes the Chlorophyceae, Trebouxiophyceae, Ulvophyceae, and Prasinopohyceae, whereas the Streptophyta includes the Charophyceae plus the bryophytes, ferns, and all other multicellular land plants (Embryophyta). The Prasinophyceae is believed to contain the earliest divergences within the green lineage. Phylogenetic analyses using rDNA sequences identify the prasinophytes as a paraphyletic taxon that diverges at the base of the Chlorophyta. rDNA analyses, however, provide ambiguous results regarding the identity of the flagellate ancestor of the Streptophyta. We have sequenced the actin-encoding cDNAs from Scherffelia dubia (Prasinophyceae), Coleochaete scutata, Spirogyra sp. (Charophyceae), and the single-copy actin gene from Mesostigma viride (Prasinophyceae). Phylogenetic analyses show Mesostigma to be the earliest divergence within the Streptophyta and provide direct evidence for a scaly, biflagellate, unicellular ancestor for this lineage. This result is supported by the existence of two conserved actin-coding region introns (positions 20-3, 152-1), and one intron in the 5'-untranslated region of the actin gene shared by Mesostigma and the embryophytes.}, } @article {pmid9795100, year = {1998}, author = {Ikuta, T and Sogawa, N and Ariga, H and Ikemura, T and Matsumoto, K}, title = {Structural analysis of mouse tenascin-X: evolutionary aspects of reduplication of FNIII repeats in the tenascin gene family.}, journal = {Gene}, volume = {217}, number = {1-2}, pages = {1-13}, doi = {10.1016/s0378-1119(98)00355-2}, pmid = {9795100}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Cell Line ; Conserved Sequence ; Crosses, Genetic ; *Evolution, Molecular ; Exons ; *Gene Duplication ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Molecular Sequence Data ; *Phylogeny ; Protein Isoforms/chemistry/genetics ; Repetitive Sequences, Nucleic Acid ; Sequence Alignment ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Stem Cells/metabolism ; Tenascin/chemistry/*genetics ; Transcription Factors/metabolism ; }, abstract = {Tenascin-X (TNX) is an extracellular matrix glycoprotein involved in both primary structural functions and modulating cellular activities in multicellular organisms. We determined the 67977bp nucleotide sequence of the entire mouse tenascin-X (Tnx) gene, which also includes the last exon of Creb-rp and Cyp21. We compared it with the orthologous human locus. Conservation of both position and orientation of the three functionally unrelated genes at this position was found. Comparison also revealed that introns 1, 4 and 6 of Tnx are highly conserved between species. The sequence showed that mouse Tnx contains 43 exons separated by 42 introns. The deduced amino-acid sequence (4114 residues) revealed that mouse Tnx has a primary structure characteristic of tenascins, which consists of a signal peptide and four heptad repeats followed by 18.5 epidermal growth factor-like (EGF) repeats, 31 fibronectin type III-like (FNIII) repeats, and a region homologous to fibrinogen. cDNA clones generated by alternative splicing of eight consecutive FNIII repeats (M15-M22) as well as a proximal FNIII repeat (M3) were also identified. The FNIII motifs that were subject to alternative splicing were assigned to the group of recently reduplicated FNIII repeats because they have a high level of amino-acid sequence similarity. We also analyzed the evolution of FNIII repeats in TNX.}, } @article {pmid9766962, year = {1998}, author = {Huai, H and Woodruff, RC}, title = {Clusters of new identical mutants and the fate of underdominant mutations.}, journal = {Genetica}, volume = {102-103}, number = {1-6}, pages = {489-505}, pmid = {9766962}, issn = {0016-6707}, mesh = {Alleles ; Animals ; *Biological Evolution ; Cluster Analysis ; Genetics, Population ; Genotype ; Germ Cells/physiology ; Heterozygote ; Humans ; Mathematical Computing ; Meiosis ; Mitosis ; *Models, Genetic ; *Mutation ; Probability ; Selection, Genetic ; }, abstract = {Given favorable environmental and demographic conditions, premeiotic clusters of identical mutations can produce a broad distribution of the initial frequency of underdominant alleles. Because of these clusters, new underdominant mutations may not necessarily be as rare in a population as previously assumed. The fixation of underdominant mutations, especially those with low heterozygous fitness, is increased when mutations appear in a cluster due to a genetic change that occurred before germline differentiation. Most restrictions on the fixation of underdominant mutations in a single population, such as strong genetic drift, weak selection against mutant heterozygotes, isolated population structure, inbreeding, meiotic drive, and selection in favor of mutant homozygotes can be relaxed or even dropped. Instead, the fate of strong underdominant mutations is determined mainly by ecological and genetic factors that affect the cluster size distribution of new premeiotic mutations. Accumulation of reproductive isolation by the fixation of underdominant mutations becomes more feasible with clusters, and mutation is not always the weakest force during this evolutionary process. The large mean and variance of reproductive success in many multicellular species make it possible that even underdominant mutations with very low heterozygous fitness could contribute substantially to reproductive isolation.}, } @article {pmid9766961, year = {1998}, author = {Furusawa, M and Doi, H}, title = {Asymmetrical DNA replication promotes evolution: disparity theory of evolution.}, journal = {Genetica}, volume = {102-103}, number = {1-6}, pages = {333-347}, pmid = {9766961}, issn = {0016-6707}, mesh = {Animals ; *Biological Evolution ; DNA/chemistry ; *DNA Replication ; Genetic Variation ; Genome ; Humans ; *Models, Genetic ; *Mutagenesis ; *Mutation ; Nucleic Acid Conformation ; Replication Origin ; }, abstract = {Heredity is guaranteed by faithful DNA replication whereas evolution depends upon errors accompanying DNA replication. This contradiction existing between heredity and evolution cannot be resolved in an individual organism, but only in terms of a population, in that a delicate balance exists between wild type and variants in a population which is necessary for the survival of the species. Namely, there seems to be a key in the mechanism of DNA replication to solve some problems of evolution. DNA is replicated semiconservatively using the leading and discontinuous lagging strands. According to our 'disparity theory of evolution', the existence of a sufficient fidelity difference between the leading and lagging strands is advantageous in terms of evolution, because the diversity of genotypes is enlarged but genotypes that have occurred in the past are guaranteed. In theory, by artificially increasing the fidelity difference between the leading and lagging strand ('disparity mutator'), evolution is accelerated while avoiding the extinction of the population. Using a disparity mutator, we should be able to improve living things, including multicellular organisms, within constrained conditions. A double-stranded algorithm, which mimics the structure and replication manner of DNA, is promising for solving optimization problems.}, } @article {pmid9766446, year = {1998}, author = {Wilkins, BS and Jones, DB}, title = {Immunophenotypic characterization of stromal cells in aspirated human bone marrow samples.}, journal = {Experimental hematology}, volume = {26}, number = {11}, pages = {1061-1067}, pmid = {9766446}, issn = {0301-472X}, mesh = {Actins/*analysis ; Biopsy ; Bone Marrow Cells/*immunology ; Cell Adhesion/immunology ; Cell Separation ; Dendritic Cells/chemistry/immunology ; Endothelium, Vascular/chemistry/cytology/immunology ; Humans ; Immunohistochemistry ; Immunophenotyping ; Macrophages/chemistry/immunology ; Receptors, Nerve Growth Factor/*analysis ; Stromal Cells/immunology ; Suction ; }, abstract = {The presence of stromal cells was investigated in aspirated bone marrow prepared by the same method as that used for the initiation of human long-term bone marrow culture (hLTBMC). In previous studies, we performed immunocytochemical staining of cytocentrifuge cell preparations using a panel of antibodies with which we characterized stromal cell populations in hLTBMC. This approach allowed morphological as well as immunophenotypic assessment of cells of interest. Morphologically distinctive cell populations expressing vascular cell adhesion molecule-1 and low-affinity nerve growth factor receptor (NGFR) were observed to be present, but no cells expressing alpha-smooth muscle actin were found. Few macrophages were present, consistent with the origin of hLTBMC stroma-adherent macrophages from monocytes and their precursor cells rather than from mature macrophages among the culture-initiating cells. In the absence of double immunostaining, it was not possible to deduce whether CD34+ cells, which were present in varying numbers in the cytocentrifuge preparations, included stromal as well as primitive hematopoietic cells. In addition to single cells, multicellular tissue fragments containing a variety of stromal cell types were detected in many samples. Their presence raises the possibility that at least some components of hLTBMC stroma may arise by explant growth from complex tissue fragments containing vascular and fibroblastic elements. Overall, our results indicate that demonstration of a variety of stroma-associated antigens, in particular NGFR, provides a useful new tool for identifying stromal elements in aspirated bone marrow.}, } @article {pmid9765291, year = {1998}, author = {Johnson, JD and Mehus, JG and Tews, K and Milavetz, BI and Lambeth, DO}, title = {Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes.}, journal = {The Journal of biological chemistry}, volume = {273}, number = {42}, pages = {27580-27586}, doi = {10.1074/jbc.273.42.27580}, pmid = {9765291}, issn = {0021-9258}, mesh = {Amino Acid Sequence ; Animals ; Cloning, Molecular ; Columbidae ; Eukaryotic Cells/enzymology ; Evolution, Molecular ; Expressed Sequence Tags ; Humans ; Mice ; Molecular Sequence Data ; Phylogeny ; Protein Conformation ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Species Specificity ; Succinate-CoA Ligases/classification/*genetics ; Swine ; Tissue Distribution ; }, abstract = {Highly ATP- and GTP-specific isoforms of succinyl-CoA synthetase in pigeon incorporate the same alpha-subunit, but different beta-subunits (Johnson, J. D., Muhonen, W. W., and Lambeth, D. O. (1998) J. Biol. Chem. 273, 27573-27579). The sequences of the mature subunits were determined by methods based on reverse transcription-polymerase chain reaction. The 306-residue mature alpha-subunit in pigeon shows >88% identity to its homologues in pig and rat. The sequences of the mature ATP- and GTP-specific beta-subunits (A-beta and G-beta, respectively) in pigeon are 54% identical. These sequences were used to identify expressed sequence tags for human and mouse that were highly homologous to G-beta and A-beta, respectively. The sequences for mature A-beta and G-beta in mouse and human were completed and verified by polymerase chain reaction. The sequence of A-beta in pig was also obtained. The mammalian A-beta sequences show >89% identity to each other; the G-beta sequences are similarly related. However, pairwise comparisons of the A-beta and G-beta sequences revealed <53% identity. Alignment with two sequences of the beta-subunit in Caenorhabditis elegans suggests that the A-beta and G-beta genes arose by duplication early in the evolution of multicellular eucaryotes. The expression of A-beta is strong in numerous mouse and human tissues, which suggests that ATP-specific succinyl-CoA synthetase also plays an important role in species throughout the animal kingdom.}, } @article {pmid9759360, year = {1998}, author = {Tordjmann, T and Tran, D and Berthon, B and Jacquemin, E and Guillon, G and Combettes, L and Claret, M}, title = {[Intracellular calcium channels, hormone receptors and intercellular calcium waves].}, journal = {Comptes rendus des seances de la Societe de biologie et de ses filiales}, volume = {192}, number = {1}, pages = {149-157}, pmid = {9759360}, issn = {0037-9026}, mesh = {Animals ; Calcium/*metabolism ; Calcium Channels/*physiology ; *Cell Communication/drug effects ; Cells, Cultured ; Fluorescent Dyes ; Fura-2 ; Hormones/*pharmacology ; Liver/*metabolism ; Microscopy, Video ; Models, Biological ; Rats ; Receptors, Cell Surface/*physiology ; Signal Transduction/drug effects ; }, abstract = {The hormone-mediated intercellular Ca2+ waves were analyzed in multiplets of rat hepatocytes by video imaging of fura2 fluorescence. These multicellular systems are composed of groups of several cells (doublets to quintuplets) issued from the liver cell plate, a one cell-thick cord of about 20 hepatocytes long between portal and centrolobular veins. When the multiplets were homogeneously bathed with the glycogenolytic agonists vasopressin, noradrenaline, angiotensin II and ATP, they showed highly organized Ca2+ signals. Surprisingly, for a given agonist, the primary rises in intracellular Ca2+ concentration ([Ca2+]i) originated invariably in the same hepatocyte, then was propagated in a sequential manner to the nearest connected cells (cell 2, then 3, cell 4 in a quadruplet, for example). The sequential activation of the cells appeared to be an intrinsic property of multiplets of rat hepatocytes. The same sequence was observed at each train of oscillations occurring between cells. The order of [Ca2+]i responses was modified neither by repeated additions of hormones nor by the hormonal dose. The mechanical disruption of an intermediate cell did not prevent the activation of the next cell. These results suggest that each hepatocyte in the multiplet displays its own sensitivity to the hormone and that a gradient of sensitivity between each cell could be responsible for directing the intercellular Ca2+ wave. To test this hypothesis, we selectively isolated rat hepatocytes from periportal (PP) and perivenous (PV) areas of the liver cell plate. Periportal (PP) and perivenous (PV) rat hepatocyte suspensions were loaded with quin2/AM and hormonal responses were studied in a spectrofluorimeter. Noradrenaline, angiotensin II, and vasopressin-induced [Ca2+]i rises were greater in PV than in PP hepatocytes. In contrast, PP cells were more responsive than PV cells to ATP. The function of the InsP3 receptor (InsP3R) was also studied by measuring the InsP3-mediated 45Ca2+ release from permeabilized PP and PV hepatocytes. In permeabilized PP and PV hepatocytes, internal Ca2+ stores displayed the same loading-kinetics, the responses to InsP3 were similar, and the sizes of InsP3-sensitive compartment were not different. In a further study, we investigated by video microscopy in fura2-loaded multicellular systems of rat hepatocytes, the mechanisms controlling intercellular propagation of the Ca2+ wave and coordination of Ca2+ signals induced by the different hormones. Using focal microperfusion which allows local perfusion of any cell of the multiplet, rapid agonist removal during the Ca2+ response and microinjection, we found that second messengers and [Ca2+]i rises in one hepatocyte cannot trigger Ca2+ responses in connected adjacent cells, suggesting that diffusion across gap junctions, while required for coordination, is not sufficient by itself for the propagation of the intercellular Ca2+ wave. In addition, focal microperfusion and intermediate cell disruption experiments revealed very fine functional differences (hormonal delay, frequency of [Ca2+]i oscillations) between hormone-induced Ca2+ signals, even between two adjacent connected hepatocytes. Recent unpublished results performed in suspensions of PP and PV rat hepatocytes supported the view of a major role played by vasopressin receptors (V1a) in genesis and orientation of the Ca2+ wave. Vasopressin binding sites, V1a mRNAs detected by RNAse Protection Assay, and vasopressin-induced InsP3 production, were more abundant in PV than in PP cells. A gradient of hormone receptors could orientate the propagation of the Ca2+ wave in multicellular systems and in liver cell plate. These results suggest that the intercellular Ca2+ wave in multicellular systems of rat hepatocytes is propagated through mechanisms involving at least three factors. (ABSTRACT TRUNCATED)}, } @article {pmid9717119, year = {1998}, author = {Simon, A and Holzer, H and Hurwitz, A and Revel, A and Zentner, BS and Lossos, F and Laufer, N}, title = {Comparison of cryopreservation outcome following intracytoplasmic sperm injection and conventional in vitro fertilization.}, journal = {Journal of assisted reproduction and genetics}, volume = {15}, number = {7}, pages = {431-437}, pmid = {9717119}, issn = {1058-0468}, mesh = {Abortion, Spontaneous ; Adult ; *Cryopreservation ; Embryo Implantation ; *Embryo Transfer ; Female ; Fertilization in Vitro/*methods ; Humans ; Male ; Pregnancy ; *Pregnancy Outcome ; Retrospective Studies ; *Spermatozoa ; Survival Rate ; Zona Pellucida ; }, abstract = {PURPOSE: Our purpose was to compare the success rate of transferring frozen-thawed embryos generated from either intracytoplasmic sperm injection (ICSI) or conventional in vitro fertilization (IVF).

METHODS: A retrospective review of all frozen-thawed embryo transfer (ET) cycles between January 1995 and April 1997 was performed. There were 83 and 204 transfer cycles of frozen-thawed multicellular embryos generated from conventional IVF (group A) and ICSI (group B), respectively. The survival rate of frozen-thawed embryos and the outcome following ET in both groups were assessed.

RESULTS: The groups did not differ in age (31.7 +/- 4.6 and 30.6 +/- 6.0; mean +/- SD) or number of embryos transferred (3.5 +/- 1.1 and 3.8 +/- 1.3 for groups A and B, respectively). An acceptable pregnancy rate per ET was achieved in both groups, but the rate was significantly higher (P = 0.04) for group A than group B, 32.5 and 20%, respectively. Group A included frozen embryos of a higher quality than those of group B, but the proportion of embryos surviving after thawing was significantly higher for group B than group A (92.5 and 85.6%, respectively; P = 0.0004). The abortion rate did not differ between the two groups: 22 and 26.8% for groups A and B, respectively.

CONCLUSIONS: Although an overall high pregnancy rate was achieved following frozen-thawed ET, it was lower for cycles in which embryos had been generated from ICSI. This difference may be attributed to a lower prefreezing embryo quality in the ICSI group. Embryos originating from ICSI were not vulnerable to cryopreservation and, when implanted, resulted in a comparable abortion rate to thawed embryos of conventional IVF.}, } @article {pmid9714748, year = {1998}, author = {Cetkovic, H and Müller, IM and Müller, WE and Gamulin, V}, title = {Characterization and phylogenetic analysis of a cDNA encoding the Fes/FER related, non-receptor protein-tyrosine kinase in the marine sponge sycon raphanus.}, journal = {Gene}, volume = {216}, number = {1}, pages = {77-84}, doi = {10.1016/s0378-1119(98)00320-5}, pmid = {9714748}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Animals ; DNA, Complementary/chemistry/*genetics ; Molecular Sequence Data ; Phylogeny ; Porifera/chemistry/*enzymology/*genetics ; Protein-Tyrosine Kinases/genetics ; Proto-Oncogene Proteins/*genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; }, abstract = {In search of ancient versions of phylogenetically conserved genes/proteins, which are typical for multicellular animals, we have decided to analyse marine sponges (Porifera), the most ancient and most primitive metazoan organisms. We report here the complete nucleotide sequence of Sycon raphanus cDNA coding for a 879 aa long protein, which displays high overall similarity in primary structure and organization of domains with non-receptor tyrosine kinases (TKs) from the Fes/FER family. The encoded protein, which we named Fes/FER_SR, has a highly conserved, 260 aa long tyrosine kinase domain at the C-terminus. Amino-terminal to the catalytic domain is an 85 aa long SH2 domain. The N-terminus is over 500 aa long and displays homology only with N-terminal domains of protein-tyrosine kinases (PTKs) from the Fes/FER family. Mammalian Fes/FER proteins show around 58% overall homology with Fes/FER_SR (identity and similarity) and lower homology was found with Drosophila melanogaster Fps (FER) protein (49%). Homologies in TK, SH2 and N-terminal domains are on average 78%, 65% and 49%, respectively. Fes/FER_SR shows next to best homology with the Abl family of non-receptor PTKs, while Src-related PTKs from the fresh-water sponge Spongilla lacustris are related only distantly to Fes/FER_SR. Phylogenetic analysis shows that the S. raphanus TK is indeed the most ancient known member of the Fes/FER family of non-receptor PTKs. The role of these PTKs in signal transduction in higher animals is still enigmatic; they are present in the nucleus as well as in the cytoplasm and FER is found in all cell types examined. The function of Fes/FER_SR in sponge, the most primitive multicellular animal which lacks specialized organ systems, remains to be elucidated.}, } @article {pmid9707402, year = {1998}, author = {Wei, N and Tsuge, T and Serino, G and Dohmae, N and Takio, K and Matsui, M and Deng, XW}, title = {The COP9 complex is conserved between plants and mammals and is related to the 26S proteasome regulatory complex.}, journal = {Current biology : CB}, volume = {8}, number = {16}, pages = {919-922}, doi = {10.1016/s0960-9822(07)00372-7}, pmid = {9707402}, issn = {0960-9822}, mesh = {Adenosine Triphosphatases/chemistry/genetics ; Amino Acid Sequence ; Animals ; Arabidopsis/genetics ; *Arabidopsis Proteins ; Brassica/genetics ; COP9 Signalosome Complex ; Calcium-Calmodulin-Dependent Protein Kinases/chemistry ; Chromatography, Affinity ; Conserved Sequence ; Evolution, Molecular ; *GTP-Binding Proteins ; Humans ; Intracellular Signaling Peptides and Proteins ; JNK Mitogen-Activated Protein Kinases ; Mammals ; *Mitogen-Activated Protein Kinases ; Multiprotein Complexes ; Peptide Hydrolases/chemistry/*genetics ; *Phylogeny ; Plant Proteins/chemistry/*genetics/isolation & purification ; *Proteasome Endopeptidase Complex ; *Proteins ; *Repressor Proteins ; Signal Transduction ; }, abstract = {The COP9 complex, genetically identified in Arabidopsis as a repressor of photomorphogenesis, is composed of multiple subunits including COP9, FUS6 (also known as COP11) and the Arabidopsis JAB1 homolog 1 (AJH1) ([1-3]; unpublished observations). We have previously demonstrated the existence of the mammalian counterpart of the COP9 complex and purified the complex by conventional biochemical and immunoaffinity procedures [4]. Here, we report the molecular identities of all eight subunits of the mammalian COP9 complex. We show that the COP9 complex is highly conserved between mammals and higher plants, and probably among most multicellular eukaryotes. It is not present in the single-cell eukaryote Saccharomyces cerevisiae, however. All of the subunits of the COP9 complex contain structural features that are also present in the components of the proteasome regulatory complex and the translation initiation factor eIF3 complex. Six subunits of the COP9 complex have overall similarity with six distinct non-ATPase regulatory subunits of the 26S proteasome, suggesting that the COP9 complex and the proteasome regulatory complex are closely related in their evolutionary origin. Subunits of the COP9 complex include regulators of the Jun N-terminal kinase (JNK) and c-Jun, a nuclear hormone receptor binding protein and a cell-cycle regulator. This suggests that the COP9 complex is an important cellular regulator modulating multiple signaling pathways.}, } @article {pmid9694578, year = {1998}, author = {Reincke, M}, title = {Mutations in adrenocortical tumors.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {30}, number = {6-7}, pages = {447-455}, doi = {10.1055/s-2007-978913}, pmid = {9694578}, issn = {0018-5043}, mesh = {Adrenal Cortex Neoplasms/*genetics ; Cytogenetics ; Genes, Tumor Suppressor ; Humans ; *Mutation ; Neoplastic Syndromes, Hereditary/genetics ; Oncogenes ; }, abstract = {Silent and incidentally detected adrenocortical neoplasms are the most frequent abnormality of the adrenal cortex. The prevalence of these lesions in the general population is around 1%, increases with age and reaches 6% in the seventh decade of life. Primary adrenocortical carcinoma, on the other hand, a highly malignant tumor, is rare with an incidence of 1.7 cases per million per year. Recent progress has been achieved in the understanding of adrenocortical tumorigenesis by mapping and identification of genes responsible for hereditary tumor syndromes like the Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Carney complex and the Multiple Endocrine Neoplasia Type I. Investigation of the clonal composition of adrenal tumors demonstrates that adrenal carcinomas are generally monoclonal, whereas adrenal adenoma may be polyclonal in approximately 25% of cases. These adenomas may have a multicellular origin under the putative action of extra-adrenal and local growth factors. Oncogenes and tumor suppressor genes involved in adrenal carcinomas include mutations in the p53 tumor suppressor gene and rearrangements of the chromosomal locus 11 p15.5 associated with IGF II hyperexpression. Constitutive activation of the ACTH receptor-G protein-cAMP signal cascade does not play a role in adrenal tumor formation. Conversely, deletions of the ACTH receptor gene have been recently found in undifferentiated adenomas and in aggressive adrenocortical carcinomas. This indicates that the signaling pathways responsible for adrenocortical tumor formation are different from that of other endocrine neoplasms like pituitary and thyroid adenomas.}, } @article {pmid9651527, year = {1998}, author = {Changeux, JP and Bertrand, D and Corringer, PJ and Dehaene, S and Edelstein, S and Léna, C and Le Novère, N and Marubio, L and Picciotto, M and Zoli, M}, title = {Brain nicotinic receptors: structure and regulation, role in learning and reinforcement.}, journal = {Brain research. Brain research reviews}, volume = {26}, number = {2-3}, pages = {198-216}, doi = {10.1016/s0165-0173(97)00040-4}, pmid = {9651527}, mesh = {Allosteric Regulation ; Animals ; Binding Sites ; Brain/*physiology ; Cognition/physiology ; Evolution, Molecular ; Humans ; Learning/*physiology ; Models, Neurological ; Mutagenesis, Site-Directed ; Nerve Net/physiology ; Neurons/*physiology ; Receptors, Nicotinic/biosynthesis/chemistry/*physiology ; *Reinforcement, Psychology ; }, abstract = {The introduction, in the late sixties, of the concepts and methods of molecular biology to the study of the nervous system had a profound impact on the field, primarily through the identification of its basic molecular components. These structures include, for example, the elementary units of the synapse: neurotransmitters, neuropeptides and their receptors, but also ionic channels, intracellular second messengers and the relevant enzymes, cell surface adhesion molecules, or growth and trophic factors [21,78,81, 52,79]. Attempts to establish appropriate causal relationships between these molecular components, the actual organisation of neural networks, and a defined behavior, nevertheless, still must overcome many difficulties. A first problem is the recognition of the minimum levels of organisation, from the molecular, cellular, or multicellular (circuit) to the higher cognitive levels, that determine the given physiological and/or behavioral performance under investigation. A common difficulty (and potential source of errors of interpretation) is to relate a cognitive function to a network organization which does not possess the required structural complexity and vice-versa. Another problem is to distinguish, among the components of the system, those which are actually necessary and those which, taken together, suffice for a given behavior to take place. Identification of such a minimal set of building blocks may receive decisive insights from the elaboration of neurally plausible formal models that bring together, within a single and coherent 'artificial organism', the neuronal network, the circulating activity, and the behavior they determine (see [42,43,45,72,30]). In this communication, we shall attempt, still in a preliminary fashion, to bring together: (1) our recent knowledge on the molecular biology of brain nicotinic receptors (nAChRs) and their allosteric properties and (2) integrated behaviors, such as cognitive learning, investigated for instance with delayed-response or passive avoidance tasks that are likely to involve nAChRs in particular at the level of reinforcement (or reward) mechanisms (see [18,29,135]).}, } @article {pmid9651482, year = {1998}, author = {Ashcroft, NR and Kosinski, ME and Wickramasinghe, D and Donovan, PJ and Golden, A}, title = {The four cdc25 genes from the nematode Caenorhabditis elegans.}, journal = {Gene}, volume = {214}, number = {1-2}, pages = {59-66}, doi = {10.1016/s0378-1119(98)00228-5}, pmid = {9651482}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Caenorhabditis elegans/embryology/*genetics ; Cell Cycle Proteins/*genetics ; Cloning, Molecular ; DNA Primers/genetics ; DNA, Complementary/genetics ; Databases, Factual ; Drosophila/genetics ; Gene Expression Regulation, Developmental ; *Genes, Helminth ; Humans ; Mice ; Molecular Sequence Data ; *Multigene Family ; Phosphoprotein Phosphatases/*genetics ; Phylogeny ; Sequence Homology, Amino Acid ; cdc25 Phosphatases ; }, abstract = {During eukaryotic evolution, multicellular organisms have evolved multiple members of gene families that may display unique, partially overlapping, or redundant functions during development. More than 75% of the C. elegans genome has been sequenced, which represents approximately 95% of the coding sequences. This provides a unique opportunity to identify most, if not all, of the members of a given gene family. We have searched the C. elegans genome database for members of a key family of cell cycle regulators, the CDC25 phosphatases, and have identified four genes. The four C. elegans genes represent a larger family within a single organism than has been reported so far in Drosophila, mice and humans. An amino acid comparison revealed a high degree of similarity and identity within the phosphatase domain. This analysis also identified an expanded consensus sequence that can be used to discover new members of the CDC25 phosphatase family. However, the four C. elegans sequences display a few novel amino acid substitutions in the residues surrounding the invariant catalytic motif CX5R. These data demonstrate the value of genome database searching for identifying new members of known gene families, understanding genetic diversity, and for studying gene structure.}, } @article {pmid9608055, year = {1998}, author = {Kruse, M and Leys, SP and Müller, IM and Müller, WE}, title = {Phylogenetic position of the Hexactinellida within the phylum Porifera based on the amino acid sequence of the protein kinase C from Rhabdocalyptus dawsoni.}, journal = {Journal of molecular evolution}, volume = {46}, number = {6}, pages = {721-728}, doi = {10.1007/pl00006353}, pmid = {9608055}, issn = {0022-2844}, mesh = {*Amino Acid Sequence ; Animals ; Catalysis ; Cloning, Molecular ; DNA, Complementary/isolation & purification ; Evolution, Molecular ; Molecular Sequence Data ; *Phylogeny ; Porifera/*enzymology/*genetics ; Protein Kinase C/chemistry/*genetics ; Protein Structure, Tertiary ; Sequence Analysis ; }, abstract = {Recent analyses of genes encoding proteins typical for multicellularity, especially adhesion molecules and receptors, favor the conclusion that all metazoan phyla, including the phylum Porifera (sponges), are of monophyletic origin. However, none of these data includes cDNA encoding a protein from the sponge class Hexactinellida. We have now isolated and characterized the cDNA encoding a protein kinase C, belonging to the C subfamily (cPKC), from the hexactinellid sponge Rhabdocalyptus dawsoni. The two conserved regions, the regulatory part with the pseudosubstrate site, the two zinc fingers, and the C2 domain, as well as the catalytic domain were used for phylogenetic analyses. Sequence alignment and construction of a phylogenetic tree from the catalytic domains revealed that the yeast Saccharomyces cerevisiae and the protozoan Trypanosoma brucei are at the base of the tree, while the hexactinellid R. dawsoni branches off first among the metazoan sequences; the other two classes of the Porifera, the Calcarea (the sequence from Sycon raphanus was used) and the Demospongiae (sequences from Geodia cydonium and Suberites domuncula were used), branch off later. The statistically robust tree also shows that the two cPKC sequences from the higher invertebrates Drosophila melanogaster and Lytechinus pictus are most closely related to the calcareous sponge. This finding was also confirmed by comparing the regulatory part of the kinase gene. We suggest, that (i) within the phylum Porifera, the class Hexactinellida diverged first from a common ancestor to the Calcarea and the Demospongiae, which both appeared later, and (ii) the higher invertebrates are more closely related to the calcareous sponges.}, } @article {pmid9622931, year = {1998}, author = {Israël, L}, title = {[Malignant progression and resistance of cancer cells: an inducible survival program similar to the SOS system of unicellular organisms induced by environmental assaults].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {182}, number = {1}, pages = {49-57}, pmid = {9622931}, issn = {0001-4079}, mesh = {Bacteria/*drug effects/genetics ; Carcinogens, Environmental/*toxicity ; Cell Survival/drug effects/genetics ; Disease Progression ; Neoplasms/etiology/*pathology ; *SOS Response, Genetics ; }, abstract = {The hypothesis discussed in this paper states that defence and survival strategies of cancer cells against therapeutic approaches are similar in their mechanisms and homologous in several genes to the SOS program known in bacteria and induced by several assaults. The almost ineluctable malignant progression and its acceleration in response to various therapies should then be considered as an inducible system inherited from prokaryotes and repressed in multicellular organisms through the anti-oncogene system. The later, weakened in case of some inherited mutations yields even in sporadic cases to repeated assaults and to the decrease with time of internal defences, including antioxidant mechanisms. This theory which presents in a new perspective the biological status of cancer in the frame of Darwinian evolution and hence the strategies able to control its progression, leads itself to some predictions and testable assertions: absence of any anti-oncogene homologues in unicellular organisms, built-in weaknesses in anti-oncogenes, existence of a common repressor and a common derepressor mechanism for several distinct genes involved in cancer and in response to an environmental assault, and finally a possible transfer of drug resistance genes in malignant cells as it is the case for bacteria submitted to stress conditions.}, } @article {pmid9545461, year = {1998}, author = {Vellai, T and Takács, K and Vida, G}, title = {A new aspect to the origin and evolution of eukaryotes.}, journal = {Journal of molecular evolution}, volume = {46}, number = {5}, pages = {499-507}, doi = {10.1007/pl00006331}, pmid = {9545461}, issn = {0022-2844}, mesh = {*Biological Evolution ; DNA Replication ; Energy Metabolism ; Escherichia coli/genetics/growth & development ; Eukaryotic Cells/*physiology ; Genetic Vectors ; *Genome, Bacterial ; *Models, Biological ; Organelles/metabolism ; Prokaryotic Cells/*physiology ; }, abstract = {One of the most important omissions in recent evolutionary theory concerns how eukaryotes could emerge and evolve. According to the currently accepted views, the first eukaryotic cell possessed a nucleus, an endomembrane system, and a cytoskeleton but had an inefficient prokaryotic-like metabolism. In contrast, one of the most ancient eukaryotes, the metamonada Giardia lamblia, was found to have formerly possessed mitochondria. In sharp contrast with the traditional views, this paper suggests, based on the energetic aspect of genome organization, that the emergence of eukaryotes was promoted by the establishment of an efficient energy-converting organelle, such as the mitochondrion. Mitochondria were acquired by the endosymbiosis of ancient alpha-purple photosynthetic Gram-negative eubacteria that reorganized the prokaryotic metabolism of the archaebacterial-like ancestral host cells. The presence of an ATP pool in the cytoplasm provided by this cell organelle allowed a major increase in genome size. This evolutionary change, the remarkable increase both in genome size and complexity, explains the origin of the eukaryotic cell itself. The loss of cell wall and the appearance of multicellularity can also be explained by the acquisition of mitochondria. All bacteria use chemiosmotic mechanisms to harness energy; therefore the periplasm bounded by the cell wall is an essential part of prokaryotic cells. Following the establishment of mitochondria, the original plasma membrane-bound metabolism of prokaryotes, as well as the funcion of the periplasm providing a compartment for the formation of different ion gradients, has been transferred into the inner mitochondrial membrane and intermembrane space. After the loss of the essential function of periplasm, the bacterial cell wall could also be lost, which enabled the naked cells to establish direct connections among themselves. The relatively late emergence of mitochondria may be the reason why multicellularity evolved so slowly.}, } @article {pmid9542636, year = {1998}, author = {Sakoda, Y and Fukusho, A}, title = {Establishment and characterization of a porcine kidney cell line, FS-L3, which forms unique multicellular domes in serum-free culture.}, journal = {In vitro cellular & developmental biology. Animal}, volume = {34}, number = {1}, pages = {53-57}, pmid = {9542636}, issn = {1071-2690}, mesh = {Animals ; Cattle ; Cell Division ; *Cell Line ; Chlorocebus aethiops ; Chromosomes ; Cricetinae ; *Culture Media, Serum-Free ; Kidney/*cytology ; Mycoplasma ; Pestivirus ; Retroviridae ; *Swine ; Vero Cells ; }, abstract = {A stable porcine kidney epithelial cell line, FS-L3, was established and maintained in Eagle's minimum essential medium containing 0.295% tryptose phosphate broth, 0.5% Bacto Peptone, and 10 mM N, N-Bis (2-hydroxyethyl)-2-aminoethanesulfonic acid without any serum. The mode of chromosomes is 37 to 38. The FS-L3 cells formed fluid-filled, multicellular, three-dimensional domes on a single monolayer. The number of domes increased markedly after further cultivation. The origin of this cell line was confirmed as porcine by hybridization using PRE-1, which can be detected as a specific sequence in the porcine genome. It was also found that FS-L3 cells were free from possible adventitious viruses and mycoplasmas.}, } @article {pmid9590294, year = {1998}, author = {Matsuno, K and Eastman, D and Mitsiades, T and Quinn, AM and Carcanciu, ML and Ordentlich, P and Kadesch, T and Artavanis-Tsakonas, S}, title = {Human deltex is a conserved regulator of Notch signalling.}, journal = {Nature genetics}, volume = {19}, number = {1}, pages = {74-78}, doi = {10.1038/ng0598-74}, pmid = {9590294}, issn = {1061-4036}, mesh = {Amino Acid Sequence ; Animals ; Drosophila ; *Drosophila Proteins ; Humans ; Insect Proteins/chemistry/*metabolism ; Membrane Proteins/*metabolism ; Molecular Sequence Data ; Receptors, Notch ; Sequence Homology, Amino Acid ; *Signal Transduction ; }, abstract = {A fundamental cell-fate control mechanism regulating multicellular development is defined by the Notch-signalling pathway. Developmental and genetic studies of wild type and activated Notch-receptor expression in diverse organisms suggest that Notch plays a general role in development by governing the ability of undifferentiated precursor cells to respond to specific signals. Notch signalling has been conserved throughout evolution and controls the differentiation of a broad spectrum of cell types during development. Genetic studies in Drosophila have led to the identification of several components of the Notch pathway. Two of the positive regulators of the pathway are encoded by the suppressor of hairless [Su(H)] and deltex (dx) genes. Drosophila dx encodes a ubiquitous, novel cytoplasmic protein of unknown biochemical function. We have cloned a human deltex homologue and characterized it in parallel with its Drosophila counterpart in biochemical assays to assess deltex function. Both human and Drosophila deltex bind to Notch across species and carry putative SH3-binding domains. Using the yeast interaction trap system, we find that Drosophila and human deltex bind to the human SH3-domain containing protein Grb2 (ref. 10). Results from two different reporter assays allow us for the first time to associate deltex with Notch-dependent transcriptional events. We present evidence linking deltex to the modulation of basic helix-loop-helix (bHLH) transcription factor activity.}, } @article {pmid9520435, year = {1998}, author = {Maleszka, R and de Couet, HG and Miklos, GL}, title = {Data transferability from model organisms to human beings: insights from the functional genomics of the flightless region of Drosophila.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {95}, number = {7}, pages = {3731-3736}, pmid = {9520435}, issn = {0027-8424}, mesh = {Animals ; *Biological Evolution ; Caenorhabditis elegans/genetics ; Drosophila/*genetics ; Gene Deletion ; *Genes, Insect ; Genome, Fungal ; *Genome, Human ; Humans ; *Models, Genetic ; Molecular Sequence Data ; Saccharomyces cerevisiae/genetics ; }, abstract = {At what biological levels are data from single-celled organisms akin to a Rosetta stone for multicellular ones? To examine this question, we characterized a saturation-mutagenized 67-kb region of the Drosophila genome by gene deletions, transgenic rescues, phenotypic dissections, genomic and cDNA sequencing, bio-informatic analysis, reverse transcription-PCR studies, and evolutionary comparisons. Data analysis using cDNA/genomic DNA alignments and bio-informatic algorithms revealed 12 different predicted proteins, most of which are absent from bacterial databases, half of which are absent from Saccharomyces cerevisiae, and nearly all of which have relatives in Caenorhabditis elegans and Homo sapiens. Gene order is not evolutionarily conserved; the closest relatives of these genes are scattered throughout the yeast, nematode, and human genomes. Most gene expression is pleiotropic, and deletion studies reveal that a morphological phenotype is seldom observed when these genes are removed from the genome. These data pinpoint some general bottlenecks in functional genomics, and they reveal the acute emerging difficulties with data transferability above the levels of genes and proteins, especially with complex human phenotypes. At these higher levels the Rosetta stone analogy has almost no applicability. However, newer transgenic technologies in Drosophila and Mus, combined with coherency pattern analyses of gene networks, and synthetic neural modeling, offer insights into organismal function. We conclude that industrially scaled robogenomics in model organisms will have great impact if it can be realistically linked to epigenetic analyses of human variation and to phenotypic analyses of human diseases in different genetic backgrounds.}, } @article {pmid9569639, year = {1998}, author = {Benassi, V and Frey, F and Carton, Y}, title = {A new specific gene for wasp cellular immune resistance in Drosophila.}, journal = {Heredity}, volume = {80 (Pt 3)}, number = {}, pages = {347-352}, doi = {10.1046/j.1365-2540.1998.00303.x}, pmid = {9569639}, issn = {0018-067X}, mesh = {Animals ; Crosses, Genetic ; Drosophila melanogaster/*genetics/*immunology/parasitology ; Female ; Male ; Models, Genetic ; Sex Chromosomes ; Wasps/immunology/*pathogenicity ; }, abstract = {Larvae of Drosophila melanogaster produce a haemocytic reaction against eggs of the parasitoid, Asobara tabida, which leads to the formation of a multicellular capsule surrounding the foreign object. The same phenomenon was observed with the parasitoid, Leptopilina boulardi. Concerning the resistance of D. melanogaster to L. boulardi, a single major segregating locus with the resistant allele dominant to the susceptible one was found. The host strain susceptible to this parasitoid species was found to be highly immune reactive against the eggs of A. tabida. The inheritance of the capacity to encapsulate A. tabida was analysed by comparing reciprocal crosses made using inbred resistant and susceptible parental strains. We conclude that differences in the encapsulation capacity are inherited autosomally, with the reactive phenotype showing complete dominance over the non-reactive one. These data suggest the existence of two independent gene systems, each being concerned with the recognition of one species only.}, } @article {pmid9500911, year = {1998}, author = {Michod, RE}, title = {Origin of sex for error repair. III. Selfish sex.}, journal = {Theoretical population biology}, volume = {53}, number = {1}, pages = {60-74}, doi = {10.1006/tpbi.1997.1341}, pmid = {9500911}, issn = {0040-5809}, support = {GM55505/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Physiological Phenomena ; *DNA Repair ; Diploidy ; Environment ; Haploidy ; Models, Theoretical ; Reproduction/*physiology ; *Sex ; Yeasts/physiology ; }, abstract = {According to the repair hypothesis, sex originated as a cooperative interaction-the benefit being damage repair. As with all cooperative strategies, cooperative sex may be vulnerable to selfish mutants. The purpose of the present paper is to understand what implications such selfish mutants may have both for the origin of sex, especially in competition with asexual diploidy, and for the elaboration of the sexual cycle, especially in facultatively sexual organisms. Asexual diploids are assumed to effectively and instantaneously repair all damages without expression of deleterious recessive mutations. Costs to asexual diploidy are considered in terms of its birth rate and mortality rate. The main results of the present paper are as follows. (i) Asexual diploidy wins when the costs of diploidy are small, mortality rates low, and damage rates high. (ii) Beginning with an ancestral state in which cells are asexual haploids, the sexual life cycle would emerge before asexual diploidy as a response to increasing DNA damage. (iii) Selfish sex is a far more robust repair strategy than cooperative sex, especially in competition with asexual diploidy. (iv) Although cooperative sex is more adaptive in extreme environments characterized by high damage and high mortality, selfish sex can still invade in these regions and take the entire system to extinction. (v) Once it is present, selfish sex is stable to asexual diploidy over a wide range of parameter values and can persist in regions of parameter space forbidded to the asexual diploid. These results help to address a concern of the gene repair theory of sex, which is that efficient repair in an asexual diploid is a better strategy than sex. Data from microbes bearing on the results are discussed as is the relationship between facultative sex in multicellular organisms and selfish sex in microbes.}, } @article {pmid9562423, year = {1998}, author = {Gomez-Escobar, N and Lewis, E and Maizels, RM}, title = {A novel member of the transforming growth factor-beta (TGF-beta) superfamily from the filarial nematodes Brugia malayi and B. pahangi.}, journal = {Experimental parasitology}, volume = {88}, number = {3}, pages = {200-209}, doi = {10.1006/expr.1998.4248}, pmid = {9562423}, issn = {0014-4894}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Brugia malayi/*chemistry/genetics ; Brugia pahangi/*chemistry/genetics ; DNA, Helminth/chemistry/isolation & purification ; Exons ; Female ; Gene Expression ; Male ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; RNA, Messenger/analysis ; Sequence Alignment ; Transforming Growth Factor beta/chemistry/*genetics ; }, abstract = {Transforming growth factor-beta (TGF-beta) superfamily genes encode products controlling pattern formation, cell differentiation, and immune-mediated inflammation. Members of this superfamily are known in multicellular organisms from mammals to the model nematode Caenorhabditis elegans. Using PCR with oligonucleotides complementary to highly conserved motifs in the TGF-beta superfamily, we first isolated a genomic clone from the filarial nematode Brugia malayi. This gene, termed Bm-tgh-1 (TGF-beta homolog-1), spans 2.5 kb of genomic DNA and contains seven exons. Transcripts of this gene are poorly represented in cDNA libraries, but a full-length cDNA was isolated by RACE from B. pahangi (Bp-tgh-1). The tgh-1 genes from the two species are >98% identical at the nucleotide and amino acid levels, differing at 18/1576 base pairs and 5/428 amino acids; all nonsynonymous substitutions are in the long N-terminal propeptide. They show a high level of similarity throughout all seven exons to a C. elegans gene on cosmid T25F10. Homology to other members of the TGF-beta superfamily is restricted to the C-terminal domain which contains the mature active protein. Key features shared with other members of the superfamily include the tetrabasic proteolytic cleavage site to release an active C-terminal peptide, seven cysteines arrayed in identical fashion, and conserved sequence motifs. tgh-1 is most similar to the BMP-1 subfamily involved in developmental signaling in nematodes, insects, and vertebrates. RT-PCR on first-strand cDNA from both Brugia species, with primers specific to the 3' end, showed that tgh-1 is not expressed in the microfilarial stage, but is detectable in the mosquito-derived infective larvae and is maximal in maturing parasites around the time of molting in the mammalian host. Adult parasites show a relatively low level of expression. The identification of tgh-1, and its preferential expression in developing parasites, suggests that it may be involved in key developmental events in the complex filarial life cycle.}, } @article {pmid9543685, year = {1998}, author = {Brown, JW}, title = {Metabolic and membrane-altering toxins, molecular differentiation factors, and pheromones in the evolution and operation of endocrine-signalling systems.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {30}, number = {2}, pages = {66-69}, doi = {10.1055/s-2007-978836}, pmid = {9543685}, issn = {0018-5043}, mesh = {Animals ; Cell Differentiation ; Cell Membrane/physiology ; Endocrine System/*physiology ; Evolution, Molecular ; Pheromones/*pharmacology ; Signal Transduction/*physiology ; Toxins, Biological/*pharmacology ; }, abstract = {The endocrine systems of vertebrates and higher invertebrates may have evolved functionally from as far back on the evolutionary scale as bacteria and early multicellular organisms and their biological communities, which have been shown to produce a variety of cyclic nucleotides, peptides, fatty acids, prostaglandins and sterols with endocrine-altering effects in primative as well as more highly evolved species.}, } @article {pmid9539027, year = {1998}, author = {Trosko, JE}, title = {Hierarchical and cybernetic nature of biologic systems and their relevance to homeostatic adaptation to low-level exposures to oxidative stress-inducing agents.}, journal = {Environmental health perspectives}, volume = {106 Suppl 1}, number = {Suppl 1}, pages = {331-339}, pmid = {9539027}, issn = {0091-6765}, support = {R01 CA21104/CA/NCI NIH HHS/United States ; }, mesh = {*Adaptation, Physiological ; Animals ; Gap Junctions/physiology ; *Homeostasis ; Humans ; Neoplasms/etiology ; *Oxidative Stress ; }, abstract = {During evolution in an aerobic environment, multicellular organisms survived by adaptive responses to both the endogenous oxidative metabolism in the cells of the organism and the chemicals and low-level radiation to which they had been exposed. The defense repertoire exists at all levels of the biological hierarchy--from the molecular and biochemical level to the cellular and tissue level to the organ and organ system level. Cells contain preventive antioxidants to suppress oxidative damage to membranes. Cells also contain proteins and DNA; built-in redundancies for damaged molecules and organelles; tightly coupled redox systems; pools of reductants; antioxidants; DNA repair mechanisms and sensitive sensor molecules such as nuclear factor kappa beta; and signal transduction mechanisms affecting both transcription and post-translational modification of proteins needed to cope with oxidative stress. The biologic consequences of the low-level radiation that exceeds the background level of oxidative damage could be necrosis or apoptosis, cell proliferation, or cell differentiation. These effects are triggered by oxidative stress-induced signal transduction mechanisms--an epigenetic, not genotoxic, process. If the end points of cell proliferation, differentiation, or cell death are not seen at frequencies above background levels in an organism, it is unlikely that low-level radiation would play a role in the multistep processes of chronic diseases such as cancer. The mechanism linked to homeostatic regulation of proliferation and adaptive functions in a multicellular organism could provide protection of any one cell receiving deposited energy by the radiation tract through the sharing of reductants and by triggering apoptosis of target stem cells. Examples of the role of gap junctional intercellular communication in the adaptive response of cells and the bystander effect illustrate how the interaction of cells can modulate the effect of radiation on the single cell.}, } @article {pmid9512266, year = {1998}, author = {Braun, CB}, title = {Schreiner organs: a new craniate chemosensory modality in hagfishes.}, journal = {The Journal of comparative neurology}, volume = {392}, number = {2}, pages = {135-163}, doi = {10.1002/(sici)1096-9861(19980309)392:2<135::aid-cne1>3.0.co;2-3}, pmid = {9512266}, issn = {0021-9967}, support = {GM08107/GM/NIGMS NIH HHS/United States ; }, mesh = {Aging ; Animals ; Biological Evolution ; Chemoreceptor Cells/*cytology/ultrastructure ; Hagfishes/*anatomy & histology/physiology ; Microscopy, Electron, Scanning ; Neurites/ultrastructure ; Organ Specificity ; Sense Organs/anatomy & histology ; Skin/anatomy & histology ; Species Specificity ; }, abstract = {An extensive system of sensory organs resembling taste buds was previously known in the skin of hagfishes. These sensory organs, called here Schreiner organs, are found throughout the epidermis of both Eptatretus stoutii and Myxine glutinosa. They are found also at high densities in the prenasal sinus, nasopharyngeal duct, and pharynx, and at lower densities in the oral and velar chambers. Schreiner organs are multicellular aggregates composed of acetylated tubulin-immunoreactive receptor cells and nonimmunoreactive cells. A considerable range of variation was found in Schreiner organ morphology, but discrete classes of organs could not be recognized. Schreiner organs are innervated by all sensory trigeminal rami, the glossopharyngeal/vagal nerve, and cutaneous rami of spinal nerves, but not by the facial nerve. The central projections of these rami form a continuous tract in the trigeminal sensory zone and the dorsolateral funiculus of the spinal cord. Some Schreiner organs may be represented in the nucleus of the solitary tract, but this structure is certainly not the primary recipient zone of Schreiner organ afferents. In light of these systemic differences between vertebrate taste systems and the Schreiner organ system of hagfishes, it is concluded that Schreiner organs are not homologous to taste buds. This sensory modality of hagfishes has no direct homolog in vertebrates and appears to be a specialization of hagfishes, perhaps derived from the primitive somatosensory system of the earliest craniates.}, } @article {pmid9507443, year = {1998}, author = {Lee, TH}, title = {Cytokine networks in the pathogenesis of bronchial asthma: implications for therapy.}, journal = {Journal of the Royal College of Physicians of London}, volume = {32}, number = {1}, pages = {56-64}, pmid = {9507443}, issn = {0035-8819}, mesh = {Animals ; Asthma/*etiology/metabolism/*therapy ; Cytokines/genetics/metabolism/*physiology ; Humans ; }, abstract = {Bronchial asthma is characterised by a multicellular inflammatory process in the airways. The bronchial inflammation is orchestrated by a network of cytokines and growth factors which includes those encoded by the GM-CSF/IL-4/IL-5 gene cluster on chromosome 5. Their cellular origins are diverse and include both inflammatory and structural cells in the airways. The efficacy of glucocorticoids in the therapy of bronchial asthma may include the ability to disrupt these cytokine networks. The failure of glucocorticoids to provide benefit in some asthmatic patients may be caused by an excess of pro-inflammatory transcription factors which sequester the glucocorticoid receptor (GR), thereby preventing it from exerting its anti-inflammatory effects. Progress is being made in the elucidation of the molecular regulation of the transcription of TH2 cytokine genes. These novel insights may provide future strategies for therapeutic intervention in asthma.}, } @article {pmid9496634, year = {1998}, author = {Sumper, M and Hallmann, A}, title = {Biochemistry of the extracellular matrix of Volvox.}, journal = {International review of cytology}, volume = {180}, number = {}, pages = {51-85}, doi = {10.1016/s0074-7696(08)61770-2}, pmid = {9496634}, issn = {0074-7696}, mesh = {Algal Proteins ; Amino Acid Sequence ; Animals ; Cell Adhesion Molecules/metabolism ; Chlorophyta/metabolism/*ultrastructure ; Extracellular Matrix/*ultrastructure ; Extracellular Matrix Proteins/metabolism ; Glycoproteins/*metabolism ; Molecular Sequence Data ; }, abstract = {The volvocine algae range in complexity from unicellular Chlamydomonas to multicellular organisms in the genus Volvox. The transition from unicellularity to multicellularity in the Volvocales is a recent event in evolution. Thus, these organisms provide a unique opportunity for exploring the development of a complex extracellular matrix (ECM) from the cell wall of a unicellular ancestor. The ECM of Volvox is divided into four main zones: The flagellar, boundary, cellular, and deep zones. Each zone is defined by ultrastructure and by characteristic ECM glycoproteins. Volvox ECM is modified under developmental control or in response to external stimuli, like the sex-inducing pheromone or stress factors. The structures of more than 10 ECM glycoproteins from a single species of Volvox are now known in molecular detail and are compared to other algal and plant cell wall/ECM glycoproteins. Although usually classified as hydroxyproline-rich glycoproteins, the striking feature of all algal ECM glycoproteins is a modular composition. Rod-shaped hydroxyproline-rich modules are combined with hydroxyproline-free domains that meet the multiple functional requirements of a complex ECM. The algal ECM provides another example of the combinatorial advantage of shuffling modules that is so evident in the evolution of the metazoan ECMs.}, } @article {pmid9494527, year = {1997}, author = {Davies, CD and Müller, H and Hagen, I and Gårseth, M and Hjelstuen, MH}, title = {Comparison of extracellular matrix in human osteosarcomas and melanomas growing as xenografts, multicellular spheroids, and monolayer cultures.}, journal = {Anticancer research}, volume = {17}, number = {6D}, pages = {4317-4326}, pmid = {9494527}, issn = {0250-7005}, mesh = {Acetylgalactosamine/analysis ; Acetylglucosamine/analysis ; Animals ; Bone Neoplasms/*pathology ; Cell Culture Techniques/methods ; Cell Division ; Collagen/analysis/biosynthesis ; Extracellular Matrix/*pathology ; Extracellular Matrix Proteins/*biosynthesis ; Fibronectins/analysis/biosynthesis ; Flow Cytometry ; Humans ; Kinetics ; Melanoma/*pathology ; Mice ; Mice, Nude ; Microscopy, Fluorescence ; Osteosarcoma/*pathology ; Transplantation, Heterologous ; }, abstract = {BACKGROUND: The composition of extracellular matrix in human xenografts and spheroids were compared with the monolayer cultures from which they originated. Collagen I, fibronectin, acetylglucosamine, and acetylgalactosamine were quantitated in two osteosarcomas and one melanoma.

METHODS: Using fluorescence microscopy, extracellular matrix constituents in the cellular and extracellular compartment were measured, whereas flow cytometry measured the extracellular matrix constituents bound to the cell surface as well as the total cellular amount including intracellular and surface bound constituents.

RESULTS: The fluorescence microscopy measurements, demonstrated that the xenografts contained more or equal quantities of the extracellular matrix constituents compared with the spheroids. Flow cytometric measurements of total cellular amounts, showed that cells from xenografts usually contained more or equal amounts as the spheroid cells, which contained less or equal amounts as the monolayer cells. The surface expression of the extracellular matrix constituents increased or there were no significant differences, comparing cells grown as monolayers, spheroids, and xenografts.

CONCLUSIONS: The data shows that multicellular spheroids being an in vitro system of intermediate complexity between monolayer cultures and tumours, contain an extracellular matrix corresponding to some degree to this intermediate position.}, } @article {pmid9484905, year = {1997}, author = {Baker, ME}, title = {Steroid receptor phylogeny and vertebrate origins.}, journal = {Molecular and cellular endocrinology}, volume = {135}, number = {2}, pages = {101-107}, doi = {10.1016/s0303-7207(97)00207-4}, pmid = {9484905}, issn = {0303-7207}, mesh = {Animals ; Evolution, Molecular ; Humans ; Phylogeny ; Receptors, Steroid/*genetics ; Vertebrates/*genetics ; }, abstract = {Vertebrates appear about 500 million years ago in the fossil record. This is only 25-50 million years after the great explosion of multicellular invertebrate body plans in the early Cambrian. On a geological time scale, this interval is a 'blink of an eye', suggesting that the evolution of regulatory genes is likely to be important in the origins of vertebrates. Here we present evidence for a role of steroid receptors in this process based on a phylogenetic analysis suggesting that receptors for androgens, glucocorticoids, mineralocorticoids, and progesterone evolved from an ancestral steroid receptor gene by two successive duplications over a brief time that could have coincided with the origins of vertebrates. Moreover, the duplications of these steroid receptors may be additional evidence for the two duplications on a genome-scale that have been proposed to be important in the evolution of vertebrates. The two successive duplications of steroid receptor genes and their subsequent sequence divergence leading to steroid-specific receptors that regulate growth, development, reproduction and homeostasis in vertebrates may have been one of the events important in vertebrate survival after the Cambrian during global extinctions that occurred about 440 and 370 million years ago.}, } @article {pmid9382786, year = {1997}, author = {Kay, RR}, title = {Dictyostelium development: lower STATs.}, journal = {Current biology : CB}, volume = {7}, number = {11}, pages = {R723-5}, doi = {10.1016/s0960-9822(06)00366-6}, pmid = {9382786}, issn = {0960-9822}, mesh = {Animals ; DNA-Binding Proteins/*physiology ; Dictyostelium/cytology/*growth & development/physiology ; Signal Transduction/*physiology ; Trans-Activators/*physiology ; }, abstract = {The discovery of a STAT protein in Dictyostelium indicates that this organism uses phosphotyrosine-SH2-domain signalling during development. Such signalling is lacking in yeast and its appearance may therefore be an early step in the evolution of multicellularity.}, } @article {pmid9458335, year = {1998}, author = {Trosko, JE and Ruch, RJ}, title = {Cell-cell communication in carcinogenesis.}, journal = {Frontiers in bioscience : a journal and virtual library}, volume = {3}, number = {}, pages = {d208-36}, doi = {10.2741/a275}, pmid = {9458335}, issn = {1093-9946}, support = {CA21104/CA/NCI NIH HHS/United States ; CA57612/CA/NCI NIH HHS/United States ; P42 ES04911-09/ES/NIEHS NIH HHS/United States ; }, mesh = {Cell Communication/*physiology ; Connexins/genetics ; Gap Junctions/*physiology ; Humans ; Models, Biological ; Mutation ; Neoplasms/genetics/*physiopathology/therapy ; Oncogene Proteins/genetics ; Tumor Suppressor Proteins/genetics ; }, abstract = {To explain the complex carcinogenic process by which a single normal cell in human beings can be converted to an invasive and metastatic cancer cell, a number of experimental findings, epidemiological observations and their associated hypothesis/theories have been integrated in this review. All cancers have been generally viewed as the result of a disruption of the homeostatic regulation of a cell's ability to respond appropriately to extra-cellular signals of the body which trigger intra-cellular signal transducting mechanisms which modulate gap junctional intercellular communication between the cells within a tissue. Normal homeostatic control of these three forms of cell communication determines whether: (a) the cell remains quiescent (Go); (b) enters into the cell proliferation phase; (c) is induced to differentiate; (d) is committed to apoptose; or (e) if it is already differentiated, it can adaptively respond. During the evolution from single cell organisms to multicellular organisms, new cellular/biological functions appeared, namely, the control of cell proliferation ("contact inhibition"), the appearance of the process of differentiation from committed stem cells of the various tissues and the need for programmed cell death or apoptosis. Interestingly, cancer cells have been characterized as cells: (a) having been derived from a stem-like cell; (b) without their ability to control cell growth or without the ability to contact inhibit; (c) which can not terminally differentiate under normal conditions; and (d) having altered ability to apoptosis under normal conditions. During that evolutionary transition from the single cell organism to the multicellular organism, many new genes appeared to accompany these new cellular functions. One of these new genes was the gene coding for a membrane associated protein channel (the gap junction) which between coupled cells, allowed the passive transfer on ions and small molecular weight molecules. A family of over a dozen of these highly evolutionarily-conserved genes (the connexin genes) coded for the connexin proteins. A hexameric unit of these connexins in one cell (a connexon) couples with a corresponding connexon in a contiguous cell to join the cytoplasms. This serves to synchronize either the metabolic or electrotonic functions of cells within a tissue. Most normal cells within solid tissues have functional gap junctional intercellular communication (GJIC) (exceptions are free-standing cells such as red blood cells, neutrophils, and several, if not all, the stem cells). On the other hand, the cancer cells of solid tissues appear to have either dysfunctional homologous or heterologous GJIC. Therefore, among the many differences between a cancer cell and its normal parental cell, the carcinogenic process involves the transition from a normal, GJIC-competent cell to one that is defective in GJIC. The review examines how GJIC can be either transiently or stably modulated by endogenous or exogenesis chemicals or by oncogenes and tumor suppressor genes at the transcriptional, translational, or posttranslational levels. It also uses the gap junction as the biological structure to facilitate cellular/tissue homeostasis to be the integrator for the "stem cell" theory, "disease of differentiation theory", "initiation/promotion/progression" concepts, nature and nurture concept of carcinogenesis, the mutation/ epigenetic theories of carcinogenesis, and the oncogene/ tumor suppressor gene theories of carcinogenesis. From this background, implications to cancer prevention and cancer therapy are generated.}, } @article {pmid9468797, year = {1997}, author = {Gold, L and Singer, B and He, YY and Brody, E}, title = {SELEX and the evolution of genomes.}, journal = {Current opinion in genetics & development}, volume = {7}, number = {6}, pages = {848-851}, doi = {10.1016/s0959-437x(97)80050-0}, pmid = {9468797}, issn = {0959-437X}, mesh = {*Evolution, Molecular ; Genetic Linkage ; *Genome ; Introns ; Models, Genetic ; Proteins/physiology ; RNA/physiology ; }, abstract = {The interrupted genome structures of complex multicellular organisms have most likely changed the evolution of the regulation of metabolism and development. Wasted intron sequences make regulation of gene expression in (for example) mammals appear to be unnecessarily complicated. The recent discoveries that globular RNA molecules are very much like the antigen-combining sites of antibodies suggest that intronic RNA may be used to help solve the problems raised by this complexity.}, } @article {pmid9466374, year = {1997}, author = {Glassman, ML and Hochberg, A}, title = {Time reversal in biological systems.}, journal = {Medical hypotheses}, volume = {49}, number = {6}, pages = {505-508}, doi = {10.1016/s0306-9877(97)90069-4}, pmid = {9466374}, issn = {0306-9877}, mesh = {Animals ; *Biological Evolution ; Cell Transformation, Neoplastic ; Humans ; *Models, Biological ; Molecular Biology ; Neoplasms/pathology/physiopathology ; *Time ; }, abstract = {Fundamental physical laws provide us appropriate descriptions of the basic behavior of nature. Science possesses a hierarchical structure with various levels of complexity and organization. This extends from the physics of elementary particles and atomic constituents, to the chemistry of molecules, to the biology of the cell and multicellular levels, up to an individual and beyond. Molecular biology thus has its roots based upon fundamental physical descriptors of macromolecules and chemical reactions. The purpose of this paper is to relate an operation in physics, time reversal symmetry, to the realm of biology. This is done with regard to the process of carcinogenesis. Tumor development and progression can be considered a microcosm of evolution, on the level of an individual organism, as well as from the aspect of evolutionary lineage. The driving forces of selection inherent in malignancy can be considered to result in the emergence of a new biological species, which is characterized by reproductive immortality and a remarkable equivalence with our unicellular ancestors. Thus, by its very nature, carcinogenesis as a closed system conceptually represents a reversal of motion with respect to order, stability and evolutionary standards of time.}, } @article {pmid9459629, year = {1997}, author = {Grimm, D and Bauer, J and Hofstädter, F and Riegger, GA and Kromer, EP}, title = {Characteristics of multicellular spheroids formed by primary cultures of human thyroid tumor cells.}, journal = {Thyroid : official journal of the American Thyroid Association}, volume = {7}, number = {6}, pages = {859-865}, doi = {10.1089/thy.1997.7.859}, pmid = {9459629}, issn = {1050-7256}, mesh = {Antigens, Neoplasm/analysis ; Cell Division/physiology ; Cell Size/physiology ; DNA, Neoplasm/analysis ; Flow Cytometry ; Humans ; Immunohistochemistry ; Keratins/analysis ; Ploidies ; Spheroids, Cellular/chemistry/*cytology ; Thyroglobulin/analysis ; Thyroid Gland/*cytology/pathology ; Thyroid Neoplasms/*pathology ; Time Factors ; Tumor Cells, Cultured ; }, abstract = {Features of multicellular tumor spheroids (MCTS) differed depending on their types of cells. MCTS formed by 4000 human thyroid primary culture epithelial tumor cells displayed diameters between 0.31 and 0.33 mm within 2 days regardless of the stage of malignancy of the originating tumors. Their cellular composition reflected that of the originating tumor in regard to DNA content and the expression of cytokeratin, vimentin, as well as thyroglobulin. During the following 3 weeks, their sizes increased up to diameters of 0.42 mm when their cells had been derived from carcinomas, and MCTS originating from adenomas stopped growing within the next 2 days. After 8 days of incubation, proliferating cells were only found in carcinoma MCTS. The cells were randomly distributed over the total volume of the spheroids, which displayed irregular cell arrangements but not concentric cell layers and did not form necrotic centers.}, } @article {pmid9449485, year = {1997}, author = {Tuominen, H and Pöllänen, R and Kallioinen, M}, title = {Multicellular origin of tenascin in skin tumors--an in situ hybridization study.}, journal = {Journal of cutaneous pathology}, volume = {24}, number = {10}, pages = {590-596}, doi = {10.1111/j.1600-0560.1997.tb01089.x}, pmid = {9449485}, issn = {0303-6987}, mesh = {Carcinoma, Basal Cell/metabolism/pathology ; Carcinoma, Squamous Cell/metabolism/pathology ; Humans ; In Situ Hybridization ; Keratosis/metabolism/pathology ; Lymphatic Metastasis/pathology ; Melanoma/metabolism/pathology/secondary ; Nevus, Pigmented/metabolism/pathology ; Skin/metabolism/pathology ; Skin Neoplasms/*metabolism/pathology ; Tenascin/*metabolism ; Tissue Distribution ; }, abstract = {Tenascin mRNA expression was studied by an in situ hybridization method in 27 skin tumors. Tenascin synthesis was increased in all skin tumors when compared to uninvolved skin but there was variation in the site of cellular synthesis between different types of tumors. In melanocytic nevi and precancerous keratinocyte lesions, tenascin seemed to be of epidermal or stromal origin. In basal cell carcinoma, squamous cell carcinoma and malignant melanoma, there was tenascin synthesis also in tumor cells. These findings are in concordance with earlier studies which suggest a role of tenascin as an anti-adhesive and motility-promoting factor in malignant skin tumors.}, } @article {pmid9428609, year = {1997}, author = {Tazi, J and Rossi, F and Labourier, E and Gallouzi, I and Brunel, C and Antoine, E}, title = {DNA topoisomerase I: customs officer at the border between DNA and RNA worlds?.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {75}, number = {11-12}, pages = {786-800}, doi = {10.1007/s001090050168}, pmid = {9428609}, issn = {0946-2716}, mesh = {Animals ; DNA Topoisomerases, Type I/genetics/*physiology ; Evolution, Molecular ; Humans ; Models, Chemical ; *RNA Splicing ; }, abstract = {DNA topoisomerase I is required for the normal development of multicellular organisms, probably because it plays a role in controlling gene activity, in addition to its function in relieving tortional stress during DNA replication and transcription. The discovery of DNA topoisomerase I as a specific kinase that phosphorylates serine-arginine rich (SR) splicing factors may provide new insights into their precise function in regulating gene expression. It is clear that the splicing factors phosphorylated by DNA topoisomerase I can modulate gene expression by changing the splicing pattern of structural genes. Studies of the splicing mechanism suggest that the phosphorylation of serine residues of SR proteins contribute to their activity. As this phosphorylation can be accomplished by several kinases, it remains to be determined whether phosphorylation by DNA topoisomerase I protein kinase is the limiting step in regulating this process. The availability of specific inhibitors of DNA topoisomerase I, structurally related to the alkaloid camptothecin, have made it possible to address this question experimentally. These inhibitors, which hold great promise as antineoplastic drugs, lead to specific inhibition of SR protein phosphorylation in cultured cells. This observation will hopefully lead to improved understanding of the mechanism by which these drugs act at cellular level.}, } @article {pmid9410270, year = {1997}, author = {Tairbekov, MG and Klimovitskiĭ, VIa and Oganov, VS}, title = {[The role of gravitational force in the evolution of living systems (the biomechanical and energy aspects)].}, journal = {Izvestiia Akademii nauk. Seriia biologicheskaia}, volume = {}, number = {5}, pages = {517-530}, pmid = {9410270}, issn = {1026-3470}, mesh = {Adaptation, Physiological ; Animals ; *Biological Evolution ; Biomechanical Phenomena ; Cell Physiological Phenomena ; Energy Metabolism ; Environment ; *Gravitation ; Homeostasis ; Humans ; }, abstract = {Possible pathways of the origin and development of adaptive mechanisms in the living systems of various levels of organization are considered from the positions of biomechanics and bioenergetics. Main attention is paid to the specific feature of functional rearrangements in the living organisms during change of habitat, at the stage of their exit from water to land. The following problems of interaction between the living systems and gravity during evolution are discussed: cellular level of organization and transition to multicellularity, formation and improvement of the skeletal and skeletal-motor systems in plants and animals, and thermal homeostasis of the living organisms in the gravity field. We showed a leading role of gravity in organization of the morphofunctional status of the living organisms during their evolution.}, } @article {pmid9406022, year = {1997}, author = {Cassone, VM and Natesan, AK}, title = {Time and time again: the phylogeny of melatonin as a transducer of biological time.}, journal = {Journal of biological rhythms}, volume = {12}, number = {6}, pages = {489-497}, doi = {10.1177/074873049701200602}, pmid = {9406022}, issn = {0748-7304}, mesh = {Amino Acid Sequence ; Animals ; Circadian Rhythm/*physiology ; Humans ; Melatonin/*physiology ; Molecular Sequence Data ; Phylogeny ; Signal Transduction/*physiology ; }, abstract = {The circadian secretion of melatonin is a critical component in circadian and seasonal rhythms in many vertebrate species. This hormone is produced by photoreceptors and cell types derived from photoreceptors in vertebrate retinas and pineal complexes via circadian regulation of the biosynthetic enzymes arylalkylamine N-acetyltransferase and hydroxyindole-O-methyltransferase at both transcriptional and posttranscriptional levels. The question of whether other multicellular animals and organisms from other taxa produce melatonin in a homologously regulated pathway is at this point unclear, but preliminary evidence suggests that vertebrate and insect melatonin are produced by convergent or parallel phylogenies. The existence and function of algal and plant melatonin is worthy of further study but is unresolved at this point. In vertebrates, the role of melatonin in behavioral and systems physiology follows two phylogenetic patterns. First, the circadian regulation of visual system structures, including the hypothalamic suprachiasmatic area, the inner retina, and retinorecipient and integrative visual structures, is a primitive characteristic among vertebrate species. Second, the relative loss of visual regulation and the presence of melatonin binding in the pars tuberalis of the adenohypophysis among mammals is a derived characteristic because these characteristics are present in this group only.}, } @article {pmid9398656, year = {1997}, author = {Filippov, V and Filippova, M and Gill, SS}, title = {Functional characterization of RNase H1 from Drosophila melanogaster.}, journal = {Biochemical and biophysical research communications}, volume = {240}, number = {3}, pages = {844-849}, doi = {10.1006/bbrc.1997.7756}, pmid = {9398656}, issn = {0006-291X}, support = {AI 32572/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Western ; Chromosome Mapping ; Cloning, Molecular ; Drosophila melanogaster/*enzymology/genetics ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli/genetics ; Evolution, Molecular ; Gene Expression ; In Situ Hybridization ; Kinetics ; Molecular Sequence Data ; Poly A/metabolism ; Poly T/metabolism ; Recombinant Fusion Proteins/isolation & purification/metabolism ; Ribonuclease H/*chemistry/genetics/*metabolism ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {We have cloned and functionally characterized the RNase H1 gene from D. melanogaster. The longest open reading frame consists of 5 exons that encode a 333 amino acid protein with a molecular mass of 37.1 kDa. This is the first demonstration of specific nuclease activity of a cloned RNase gene from a multicellular higher eukaryote. No additional proteins or cofactors are required for this nuclease activity. Comparison of Drosophila RNase H1 amino acid sequence to that of other cellular eukaryotic homologs reveals the presence of three evolutionarily distinct domains. The N- and C-terminal conserved domains are connected by a highly variable domain. The C-terminal domain has high amino acid similarity to bacterial RNase HI and the RNase H domain of retroviral reverse transcriptase, while the N-terminus, of unknown function, is similar to the P6 translational activator of caulimoviruses.}, } @article {pmid9342353, year = {1997}, author = {Baldauf, SL and Doolittle, WF}, title = {Origin and evolution of the slime molds (Mycetozoa).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {94}, number = {22}, pages = {12007-12012}, pmid = {9342353}, issn = {0027-8424}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Cloning, Molecular ; Dictyostelium/genetics ; Evolution, Molecular ; Fungal Proteins/*genetics ; *Genes, Fungal ; Introns ; Molecular Sequence Data ; Myxomycetes/*classification/genetics ; Peptide Elongation Factor 1 ; Peptide Elongation Factors/*genetics ; Phylogeny ; Physarum/genetics ; Polymerase Chain Reaction ; Reproducibility of Results ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; }, abstract = {The Mycetozoa include the cellular (dictyostelid), acellular (myxogastrid), and protostelid slime molds. However, available molecular data are in disagreement on both the monophyly and phylogenetic position of the group. Ribosomal RNA trees show the myxogastrid and dictyostelid slime molds as unrelated early branching lineages, but actin and beta-tubulin trees place them together as a single coherent (monophyletic) group, closely related to the animal-fungal clade. We have sequenced the elongation factor-1alpha genes from one member of each division of the Mycetozoa, including Dictyostelium discoideum, for which cDNA sequences were previously available. Phylogenetic analyses of these sequences strongly support a monophyletic Mycetozoa, with the myxogastrid and dictyostelid slime molds most closely related to each other. All phylogenetic methods used also place this coherent Mycetozoan assemblage as emerging among the multicellular eukaryotes, tentatively supported as more closely related to animals + fungi than are green plants. With our data there are now three proteins that consistently support a monophyletic Mycetozoa and at least four that place these taxa within the "crown" of the eukaryote tree. We suggest that ribosomal RNA data should be more closely examined with regard to these questions, and we emphasize the importance of developing multiple sequence data sets.}, } @article {pmid9315669, year = {1997}, author = {Kooistra, R and Vreeken, K and Zonneveld, JB and de Jong, A and Eeken, JC and Osgood, CJ and Buerstedde, JM and Lohman, PH and Pastink, A}, title = {The Drosophila melanogaster RAD54 homolog, DmRAD54, is involved in the repair of radiation damage and recombination.}, journal = {Molecular and cellular biology}, volume = {17}, number = {10}, pages = {6097-6104}, pmid = {9315669}, issn = {0270-7306}, mesh = {Amino Acid Sequence ; Animals ; DNA Damage ; DNA Helicases ; DNA Repair/*physiology ; DNA-Binding Proteins/*genetics/physiology ; *Drosophila Proteins ; Drosophila melanogaster/embryology/*genetics/growth & development ; *Egg Proteins ; Eye/embryology ; Female ; Gene Expression Regulation, Developmental ; Genes, Insect/genetics/physiology ; Larva/drug effects/radiation effects ; Male ; Methyl Methanesulfonate/pharmacology ; Mitosis/genetics ; Molecular Sequence Data ; Mutagenesis ; Mutagens/pharmacology ; RNA, Messenger/analysis ; Recombination, Genetic/*physiology ; Sequence Homology, Amino Acid ; }, abstract = {The RAD54 gene of Saccharomyces cerevisiae plays a crucial role in recombinational repair of double-strand breaks in DNA. Here the isolation and functional characterization of the RAD54 homolog of the fruit fly Drosophila melanogaster, DmRAD54, are described. The putative Dmrad54 protein displays 46 to 57% identity to its homologs from yeast and mammals. DmRAD54 RNA was detected at all stages of fly development, but an increased level was observed in early embryos and ovarian tissue. To determine the function of DmRAD54, a null mutant was isolated by random mutagenesis. DmRADS4-deficient flies develop normally, but the females are sterile. Early development appears normal, but the eggs do not hatch, indicating an essential role for DmRAD54 in development. The larvae of mutant flies are highly sensitive to X rays and methyl methanesulfonate. Moreover, this mutant is defective in X-ray-induced mitotic recombination as measured by a somatic mutation and recombination test. These phenotypes are consistent with a defect in the repair of double-strand breaks and imply that the RAD54 gene is crucial in repair and recombination in a multicellular organism. The results also indicate that the recombinational repair pathway is functionally conserved in evolution.}, } @article {pmid9232818, year = {1997}, author = {Müller, WE}, title = {Origin of metazoan adhesion molecules and adhesion receptors as deduced from cDNA analyses in the marine sponge Geodia cydonium: a review.}, journal = {Cell and tissue research}, volume = {289}, number = {3}, pages = {383-395}, doi = {10.1007/s004410050885}, pmid = {9232818}, issn = {0302-766X}, mesh = {Animals ; Cell Adhesion Molecules/*genetics ; DNA, Complementary/analysis ; Membrane Glycoproteins ; Membrane Proteins/*genetics ; Platelet Glycoprotein GPIb-IX Complex ; Porifera/*chemistry ; }, abstract = {The phylogenetic relationships of the kingdom Animalia (Metazoa) have long been questioned. Whether the lowest eukaryotic multicellular organisms, the metazoan phylum Porifera (sponges), independently evolved multicellularity from a separate protist lineage (polyphyly of animals) or whether they were derived from the same protist group as the other animal phyla (monophyly) remains unclear. Analyses of the genes that are typical for multicellularity, e.g. those coding for adhesion molecules (galectin) and adhesion receptors (receptor tyrosine kinase, integrin receptor, receptors featuring scavenger receptor cysteine-rich domains) or elements involved in signal transduction pathways (G-proteins, Ser/Thr protein kinases), especially from the marine sponge Geodia cydonium, indicate that all animals, including sponges, are of monophyletic origin.}, } @article {pmid9288632, year = {1997}, author = {Ko, HM and Choi, C and Park, CS and Juhng, SW}, title = {Analysis of clonality by X chromosome inactivation in uterine cervix cancer.}, journal = {Journal of Korean medical science}, volume = {12}, number = {4}, pages = {322-326}, doi = {10.3346/jkms.1997.12.4.322}, pmid = {9288632}, issn = {1011-8934}, mesh = {Carcinoma in Situ/*genetics/pathology ; Carcinoma, Squamous Cell/*genetics/pathology ; Disease Progression ; *Dosage Compensation, Genetic ; Female ; Humans ; Neoplasm Invasiveness ; Paraffin Embedding ; Polymerase Chain Reaction/*methods ; Receptors, Androgen/*genetics ; Uterine Cervical Neoplasms/*genetics/pathology ; }, abstract = {The determination of a unicellular or a multicellular origin of a tumor is an important due for understanding its etiology. To investigate this issue, we performed clonality assay of cervix cancer using polymerase chain reaction based on highly polymorphic locus of the androgen receptor gene, in which methylation of DNA correlates with inactivation of X chromosome. DNA samples were obtained from formalin-fixed, paraffin-embedded tissue of 20 invasive epidermoid carcinomas and 10 carcinoma in situ. Seven of ten carcinoma in situ, heterozygous for the androgen receptor locus, were monoclonal pattern. Among twenty invasive epidermoid carcinomas, eighteen of which showed heterozygous, twelve were monoclonal pattern and six were polyclonal pattern. We conclude that carcinoma in situ arises from a single cell. In invasive epidermoid carcinoma, most cases were monoclonal, although some cases were polyclonal. These suggest that invasive carcinoma of the cervix does not always arise from a single cell, but may arise from several cells with different mechanisms.}, } @article {pmid9270303, year = {1997}, author = {Nicholson, DW and Thornberry, NA}, title = {Caspases: killer proteases.}, journal = {Trends in biochemical sciences}, volume = {22}, number = {8}, pages = {299-306}, doi = {10.1016/s0968-0004(97)01085-2}, pmid = {9270303}, issn = {0968-0004}, mesh = {Amino Acid Sequence ; Animals ; Apoptosis/*physiology ; Caenorhabditis elegans/*enzymology/genetics ; *Cysteine Endopeptidases/chemistry/metabolism ; Molecular Sequence Data ; Substrate Specificity ; }, abstract = {Caspases (cysteinyl aspartate-specific proteinases) mediate highly specific proteolytic cleavage events in dying cells, which collectively manifest the apoptotic phenotype. The key and central role that these enzymes play in a biochemical cell-suicide pathway has been conserved throughout the evolution of multicellular eukaryotes.}, } @article {pmid9255794, year = {1997}, author = {Helmlinger, G and Netti, PA and Lichtenbeld, HC and Melder, RJ and Jain, RK}, title = {Solid stress inhibits the growth of multicellular tumor spheroids.}, journal = {Nature biotechnology}, volume = {15}, number = {8}, pages = {778-783}, doi = {10.1038/nbt0897-778}, pmid = {9255794}, issn = {1087-0156}, support = {R35-CA-56591/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Cell Count ; Cell Division ; Humans ; Mice ; *Models, Biological ; Neoplasms, Experimental/*pathology ; Stress, Mechanical ; Tumor Cells, Cultured ; }, abstract = {In normal tissues, the processes of growth, remodeling, and morphogenesis are tightly regulated by the stress field; conversely, stress may be generated by these processes. We demonstrate that solid stress inhibits tumor growth in vitro, regardless of host species, tissue of origin, or differentiation state. The inhibiting stress for multicellular tumor spheroid growth in agarose matrices was 45 to 120 mm Hg. This stress, which greatly exceeds blood pressure in tumor vessels, is sufficient to induce the collapse of vascular or lymphatic vessels in tumors in vivo and can explain impaired blood flow, poor lymphatic drainage, and suboptimal drug delivery previously reported in solid tumors. The stress-induced growth inhibition of plateau-phase spheroids was accompanied, at the cellular level, by decreased apoptosis with no significant changes in proliferation. A concomitant increase in the cellular packing density was observed, which may prevent cells from undergoing apoptosis via a cell-volume or cell-shape transduction mechanism. These results suggest that solid stress controls tumor growth at both the macroscopic and cellular levels, and thus influences tumor progression and delivery of therapeutic agents.}, } @article {pmid9223263, year = {1997}, author = {Ayala, FJ}, title = {Vagaries of the molecular clock.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {94}, number = {15}, pages = {7776-7783}, pmid = {9223263}, issn = {0027-8424}, support = {GM42397/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Glycerolphosphate Dehydrogenase/*genetics ; Species Specificity ; Superoxide Dismutase/*genetics ; }, abstract = {The hypothesis of the molecular evolutionary clock asserts that informational macromolecules (i.e., proteins and nucleic acids) evolve at rates that are constant through time and for different lineages. The clock hypothesis has been extremely powerful for determining evolutionary events of the remote past for which the fossil and other evidence is lacking or insufficient. I review the evolution of two genes, Gpdh and Sod. In fruit flies, the encoded glycerol-3-phosphate dehydrogenase (GPDH) protein evolves at a rate of 1.1 x 10(-10) amino acid replacements per site per year when Drosophila species are compared that diverged within the last 55 million years (My), but a much faster rate of approximately 4.5 x 10(-10) replacements per site per year when comparisons are made between mammals (approximately 70 My) or Dipteran families (approximately 100 My), animal phyla (approximately 650 My), or multicellular kingdoms (approximately 1100 My). The rate of superoxide dismutase (SOD) evolution is very fast between Drosophila species (16.2 x 10(-10) replacements per site per year) and remains the same between mammals (17.2) or Dipteran families (15.9), but it becomes much slower between animal phyla (5.3) and still slower between the three kingdoms (3.3). If we assume a molecular clock and use the Drosophila rate for estimating the divergence of remote organisms, GPDH yields estimates of 2,500 My for the divergence between the animal phyla (occurred approximately 650 My) and 3,990 My for the divergence of the kingdoms (occurred approximately 1,100 My). At the other extreme, SOD yields divergence times of 211 My and 224 My for the animal phyla and the kingdoms, respectively. It remains unsettled how often proteins evolve in such erratic fashion as GPDH and SOD.}, } @article {pmid9236106, year = {1997}, author = {Niu, DK and Chen, JK}, title = {Evolutionary advantages of cell specialization: save and protect DNA.}, journal = {Journal of theoretical biology}, volume = {187}, number = {1}, pages = {39-43}, doi = {10.1006/jtbi.1997.0410}, pmid = {9236106}, issn = {0022-5193}, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation ; Cell Division ; *Cell Physiological Phenomena ; Cell Survival ; *DNA ; Germ Cells/physiology ; *Models, Genetic ; }, abstract = {As the transcribed regions of nuclear DNA are in a more open state, they are liable to be damaged by naturally or environmentally produced mutagens. Cell specializations make it possible to express fewer genes in individual cells of multicellular organisms, thus protecting genes from the damage of mutagens. We propose that this might account for the advantage of cell specialization, as an alternative to the traditional conception that cell specializations result in increased efficiency. The most efficient cell specialization to protect DNA is in the segregation of germ cell(s) and somatic cell(s). But in optimal environments, such specialization is expected to reduce the rate of reproduction, which might counteract its advantage of protecting DNA.}, } @article {pmid9282314, year = {1997}, author = {Boxberger, HJ and Meyer, TF and Grausam, MC and Reich, K and Becker, HD and Sessler, MJ}, title = {Isolating and maintaining highly polarized primary epithelial cells from normal human duodenum for growth as spheroid-like vesicles.}, journal = {In vitro cellular & developmental biology. Animal}, volume = {33}, number = {7}, pages = {536-545}, pmid = {9282314}, issn = {1071-2690}, mesh = {Antibodies, Monoclonal ; *Cell Division ; *Cell Polarity ; *Cell Separation ; Cells, Cultured ; Collagen/analysis ; Duodenum/*cytology ; Epithelial Cells ; Flow Cytometry ; Humans ; Immunohistochemistry ; Intestinal Mucosa/*cytology ; Laminin/analysis ; *Liposomes ; Microscopy, Electron ; Microscopy, Electron, Scanning ; }, abstract = {A method is described for the three-dimensional (3-D) in vitro culture of nontransformed gastrointestinal epithelial cells from the human duodenal mucosa. Biopsies obtained from human duodenum were finely minced. The tissue fragments were suspended in culture medium supplemented with 5% fetal calf serum and the appropriate antibiotics. The suspended mucosal fragments generated spheroid-like multicellular vesicles consisting of highly prismatic absorptive and goblet cells retaining most of the histological features of the tissue in vivo. We performed immunocytochemical studies to determine the origin of the vesicles using monoclonal antibodies against EP4. The histochemistry of the vesicles showed alkaline phosphatase activity. Ultrastructural studies revealed that these cells exhibit characteristics of normal duodenal cells in vivo: apical microvilli, glycocalyx, tight junctions and desmosomes, lateral membrane interdigitations, mucous droplets, and a well-developed Golgi apparatus. An overgrowth of the vesicles by fibroblasts was not seen during cultivation. In contrast with the two-dimensional cell cultures grown on artificial supports, the vesicle cells show organization similar to that of natural epithelia. The polarization and cytoarchitecture of normal gastrointestinal epithelial cells cultured as 3-D vesicles are comparable to those known for the native tissue. This study was undertaken to provide a morphological baseline for subsequent infection experiments.}, } @article {pmid9246642, year = {1997}, author = {Hegyi, H and Bork, P}, title = {On the classification and evolution of protein modules.}, journal = {Journal of protein chemistry}, volume = {16}, number = {5}, pages = {545-551}, pmid = {9246642}, issn = {0277-8033}, mesh = {Amino Acid Sequence ; Animals ; Genome ; Humans ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Tertiary ; Proteins/chemistry/*classification/*physiology ; }, abstract = {Our efforts to classify the functional units of many proteins, the modules, are reviewed. The data from the sequencing projects for various model organisms are extremely helpful in deducing the evolution of proteins and modules. For example, a dramatic increase of modular proteins can be observed from yeast to C. elegans in accordance with new protein functions that had to be introduced in multicellular organisms. Our sequence characterization of modules relies on sensitive similarity search algorithms and the collection of multiple sequence alignments for each module. To trace the evolution of modules and to further automate the classification, we have developed a sequence and a module alerting system that checks newly arriving sequence data for the presence of already classified modules. Using these systems, we were able to identify an unexpected similarity between extracellular C1Q modules with bacterial proteins.}, } @article {pmid9225477, year = {1997}, author = {Michod, RE and Roze, D}, title = {Transitions in individuality.}, journal = {Proceedings. Biological sciences}, volume = {264}, number = {1383}, pages = {853-857}, pmid = {9225477}, issn = {0962-8452}, support = {GM-55505/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; Animals ; *Biological Evolution ; Haploidy ; Individuality ; *Models, Genetic ; Selection, Genetic ; }, abstract = {The evolution of multicellular organisms is the premier example of the integration of lower levels into a single, higher-level individual. Explaining the evolutionary transition from single cells to multicellular organisms is a major challenge for evolutionary theory. We provide an explicit two locus genetic framework for understanding this transition in terms of the increase of cooperation among cells and the regulation of conflict within the emerging organism. Heritability of fitness and individuality at the new level emerge as a result of the evolution of organismal functions that restrict the opportunity for conflict within and ensure cooperation among cells. Conflict leads, through the evolution of adaptations that reduce it, to greater individuality and harmony for the organism.}, } @article {pmid9200609, year = {1997}, author = {Kawata, T and Shevchenko, A and Fukuzawa, M and Jermyn, KA and Totty, NF and Zhukovskaya, NV and Sterling, AE and Mann, M and Williams, JG}, title = {SH2 signaling in a lower eukaryote: a STAT protein that regulates stalk cell differentiation in dictyostelium.}, journal = {Cell}, volume = {89}, number = {6}, pages = {909-916}, doi = {10.1016/s0092-8674(00)80276-7}, pmid = {9200609}, issn = {0092-8674}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Differentiation/physiology ; Cloning, Molecular ; DNA, Complementary ; DNA-Binding Proteins/chemistry/genetics/isolation & purification/metabolism ; Dictyostelium/cytology/growth & development/*physiology ; Gene Expression Regulation, Developmental/physiology ; Gene Expression Regulation, Fungal/physiology ; Janus Kinase 1 ; Mammals ; Mass Spectrometry ; *Milk Proteins ; Molecular Sequence Data ; Phosphorylation ; Protein-Tyrosine Kinases/metabolism ; RNA, Messenger/genetics ; Receptors, Cell Surface/metabolism ; STAT5 Transcription Factor ; Sequence Homology, Amino Acid ; Signal Transduction/*physiology ; Trans-Activators/chemistry/genetics ; Transcription Factors/chemistry/isolation & purification/metabolism ; src Homology Domains/*physiology ; }, abstract = {The TTGA-binding factor is a transcriptional regulator activated by DIF, the chlorinated hexaphenone that induces prestalk cell differentiation in Dictyostelium. The same activity also functions as a repressor, controlling stalk cell differentiation. We show that the TTGA-binding factor is a STAT protein. Like the metazoan STATs, it functions via the reciprocal interaction of a phosphotyrosine residue on one molecule with an SH2 domain on a dimerizing partner. Furthermore, it will bind specifically to a mammalian interferon-stimulated response element. In Saccharomyces cerevisiae, where the entire genomic sequence is known, SH2 domains have not been identified. It would seem, therefore, that SH2 signaling pathways arose very early in the evolution of multicellular organisms, perhaps to facilitate intercellular comunication.}, } @article {pmid9214645, year = {1997}, author = {Torkelson, J and Harris, RS and Lombardo, MJ and Nagendran, J and Thulin, C and Rosenberg, SM}, title = {Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation.}, journal = {The EMBO journal}, volume = {16}, number = {11}, pages = {3303-3311}, pmid = {9214645}, issn = {0261-4189}, mesh = {Adaptation, Biological/*genetics ; Base Sequence ; *Biological Evolution ; Chromosomes, Bacterial ; Escherichia coli/*genetics/growth & development ; F Factor/genetics ; *Genome, Bacterial ; Lac Operon/genetics ; Models, Genetic ; Molecular Sequence Data ; *Mutagenesis ; *Recombination, Genetic ; Selection, Genetic ; Time Factors ; }, abstract = {Stationary-phase mutation in microbes can produce selected ('adaptive') mutants preferentially. In one system, this occurs via a distinct, recombination-dependent mechanism. Two points of controversy have surrounded these adaptive reversions of an Escherichia coli lac mutation. First, are the mutations directed preferentially to the selected gene in a Lamarckian manner? Second, is the adaptive mutation mechanism specific to the F plasmid replicon carrying lac? We report that lac adaptive mutations are associated with hypermutation in unselected genes, in all replicons in the cell. The associated mutations have a similar sequence spectrum to the adaptive reversions. Thus, the adaptive mutagenesis mechanism is not directed to the lac genes, in a Lamarckian manner, nor to the F' replicon carrying lac. Hypermutation was not found in non-revertants exposed to selection. Therefore, the genome-wide hypermutation underlying adaptive mutation occurs in a differentiated subpopulation. The existence of mutable subpopulations in non-growing cells is important in bacterial evolution and could be relevant to the somatic mutations that give rise to cancers in multicellular organisms.}, } @article {pmid9204761, year = {1997}, author = {Wilson, PG and Borisy, GG}, title = {Evolution of the multi-tubulin hypothesis.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {19}, number = {6}, pages = {451-454}, doi = {10.1002/bies.950190603}, pmid = {9204761}, issn = {0265-9247}, mesh = {Animals ; Evolution, Molecular ; Humans ; Microtubules/*chemistry/genetics/ultrastructure ; Tubulin/*chemistry/genetics/ultrastructure ; }, abstract = {Microtubules are organized into diverse cellular structures in multicellular organisms. How is such diversity generated? Although highly conserved overall, variable regions within alpha- and beta-tubulins show divergence from other alpha- and beta-tubulins in the same species, but show conservation among different species. Such conservation raises the question of whether diversity in tubulin structure mediates diversity in microtubule organization. Recent studies probing the function of beta-tubulin isotypes in axonemes of insects suggest that tubulin structure, through interactions with extrinsic proteins, can direct the architecture and supramolecular organization of microtubules.}, } @article {pmid9112752, year = {1997}, author = {Ruvinsky, A}, title = {Sex, meiosis and multicellularity.}, journal = {Acta biotheoretica}, volume = {45}, number = {2}, pages = {127-141}, doi = {10.1023/a:1000334022255}, pmid = {9112752}, issn = {0001-5342}, mesh = {Animals ; *Biological Evolution ; Cell Aggregation/physiology ; Female ; Male ; Meiosis/*physiology ; *Phylogeny ; Reproduction/physiology ; *Sex ; }, abstract = {The origin and progress of multicellularity, which is one of the crucial steps in the evolution of life, remains unclear and stringent phylogenetic reconstruction of the process is difficult. However, further theoretical considerations of the problem could be useful for the creation of a verifiable hypothesis. Sex as a ubiquitous biological phenomenon is usually considered as something entirely linked with reproduction. This is mostly true for modem multicellular organisms, but at the earliest stage of evolution of eukaryotes it was not so. At that time the sexual process had nothing to do with reproduction, and only later, sex and reproduction merged together. One of the aims of this paper is to consider the sexual process as a likely basis for the establishment of multicellularity and to discuss the early stages of evolution of the multicellularity from this perspective. It is suggested that mitotic reproduction of cells at different stages of the sexual cycle of unicellular ancestors might be the starting points for independent transition to multicellularity in different taxa. Numerous consequences of these transitions, including evolution of bisexuality and development of novel meiotic functions in animals, are discussed.}, } @article {pmid9180159, year = {1997}, author = {Thorsen, F and Visted, T and Lehtolainen, P and Ylä-Herttuala, S and Bjerkvig, R}, title = {Release of replication-deficient retroviruses from a packaging cell line: interaction with glioma tumor spheroids in vitro.}, journal = {International journal of cancer}, volume = {71}, number = {5}, pages = {874-880}, doi = {10.1002/(sici)1097-0215(19970529)71:5<874::aid-ijc28>3.0.co;2-6}, pmid = {9180159}, issn = {0020-7136}, mesh = {Animals ; Brain/cytology ; Cell Aggregation ; Cell Line ; Cell Survival ; Coculture Techniques ; DNA/analysis ; Escherichia coli/genetics ; Flow Cytometry ; Glioma/*metabolism ; Humans ; Mice ; Rabbits ; Rats ; Retroviridae/*physiology ; Spheroids, Cellular/*metabolism ; *Transfection ; Tumor Cells, Cultured ; *Virus Replication ; beta-Galactosidase/genetics ; }, abstract = {The present study describes how various growth conditions affect gene expression and virus production from a retroviral packaging cell line (Liz 9), grown as monolayers and as multicellular spheroids. In addition, to study the direct interaction between packaging cells and tumor tissue of glioma origin, Liz 9 spheroids were confronted with tumor spheroids derived from a human glioma cell line, GaMg. The results show a progressive gene transfer into the tumor tissue, with 9% transfection efficacy after 5 days of co-culture. In comparison, no gene transfer was observed when the Liz 9 spheroids were confronted with normal brain-cell aggregates. The Liz 9 spheroids established from early-passage cultures (passages 7-14) showed limited growth during 28 days, whereas those initiated from late-passage monolayer cultures (passages 39-49) showed extensive growth. Flow-cytometric DNA profiles of monolayers and of spheroids indicated no difference in cell-cycle distribution or ploidy between early and late passages. A cell-viability assay using scanning confocal microscopy revealed mostly viable cells in the Liz 9 spheroids, with only a few dead cells scattered within the structures. The lacZ-gene expression was maintained in early- and in late-passage cultures. In comparison, in Liz 9 early-passage monolayers, the virus titer was 3.1 x 10(4) +/- 0.4 x 10(4) CFU/ml, whereas no virus titer was found in late-passage cultures. The virus titer from the Liz 9 spheroids was found to be between 10(3) and 10(4) CFU/ml. It is concluded that the virus production from packaging cells may vary, depending on passage number and tissue-culture conditions. In the present study, this is demonstrated by a complete loss in virus titer during prolonged culture of packaging cells. In addition, the 3-dimensional confrontation system described allows direct visualization of how packaging cells interact with tumor tissue. Thus, the co-culture system represents a model for studying the efficiency of packaging cells in transfecting heterogeneous tumor tissue in vitro.}, } @article {pmid9194029, year = {1997}, author = {Inoue, S and Takaoka, K and Endo, T and Mizuno, S and Ogawa, Y and Yoshida, M and Ohnuma, T}, title = {In vitro confirmation of newly established lung cancer cell lines using flow cytometry and multicellular tumor spheroids.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {17}, number = {1}, pages = {85-101}, doi = {10.1016/s0169-5002(97)00652-1}, pmid = {9194029}, issn = {0169-5002}, mesh = {Antigens, Neoplasm/analysis ; Carcinoembryonic Antigen/analysis ; Carcinoma, Squamous Cell/immunology ; Flow Cytometry/*methods ; Histocytochemistry ; Humans ; Immunohistochemistry ; Karyotyping ; Lung/chemistry/immunology/pathology ; Lung Neoplasms/diagnosis/genetics/*pathology ; Microscopy, Electron ; Phosphopyruvate Hydratase/analysis ; Photography ; Spheroids, Cellular/*pathology ; Tumor Cells, Cultured/cytology/*pathology/ultrastructure ; }, abstract = {We report on a simplified method of cytomorphological in vitro confirmation of newly established lung cancer cell lines by using multicellular tumor spheroids (MTS) and flow cytometry (FCM). Eleven cell lines were established from 11 patients with lung cancer. The MTS were produced by culturing cells in agar-coated dish. Cytomorphological studies were made using smears of crushed MTS and frozen sections of MTS. The MTS were fixed doubly with paraformaldehyde and osmic acid for scanning and transmission electron microscopy. Bivariate fluorescence of fluorescein isothyocyanate (FITC, tumor associated antigen, TAA) and propidium iodide (DNA) were measured by FCM. The MTS grew anchorage-independently. Cytopathological and electron microscopic findings of MTS were similar to those of the original clinical specimens. The DNA index and TAA were useful in evaluating the presence or absence of contamination by cells of non-tumor origin. The new cell lines satisfied a minimum of four conditions to confirm their establishment: (a) they originated from humans, (b) they were cytomorphologically identified with specimens from primary lesions, (c) they showed tumorigenicity, and (d) they were free from contamination by cells of different origin. From these findings, the establishment of new cell lines can be confirmed in vitro by using MTS and FCM.}, } @article {pmid9140449, year = {1997}, author = {Heim, S and Teixeira, MR and Dietrich, CU and Pandis, N}, title = {Cytogenetic polyclonality in tumors of the breast.}, journal = {Cancer genetics and cytogenetics}, volume = {95}, number = {1}, pages = {16-19}, doi = {10.1016/s0165-4608(96)00322-6}, pmid = {9140449}, issn = {0165-4608}, mesh = {Breast Neoplasms/*genetics ; *Chromosome Aberrations ; Female ; Humans ; }, abstract = {Cytogenetically unrelated clones are found in half of all carcinomas of the breast and also in the epithelial fraction of many benign breast tumors. The chromosomal aberrations thus detected are clearly nonrandom and appear to be the same as those often seen in other tumors as sole karyotypic anomalies. Clonal chromosome abnormalities are not found in histologically normal breast tissue. Cytogenetically unrelated clones may be found in both primary tumors and secondary lesions, be it within the same breast (multifocal carcinomas), in the contralateral breast (bilateral carcinomas), or in lymph node or other metastases. The aberrations are present in topologically separate tumor domains and may confer on the cells that harbor them different types of cancer-specific behavior, such as the ability to metastasize and invade locally. Whereas the available evidence thus strongly indicates that the cells carrying clonal karyotypic aberrations all are part of the neoplastic parenchyma, it is less certain whether cytogenetic polyclonality actually signifies a multicellular tumor origin, although we think that this is the explanation that best accommodates the cytogenetic data. But even if it should eventually be shown that the seemingly unrelated clones have some submicroscopic tumorigenic mutation in common, the observed karyotypic heterogeneity is remarkable and goes far beyond what one has become accustomed to from most other tumor types. To understand how the various clones interact during mammary carcinogenesis will be a major task in future breast cancer research.}, } @article {pmid9100369, year = {1997}, author = {Pancer, Z and Kruse, M and Müller, I and Müller, WE}, title = {On the origin of Metazoan adhesion receptors: cloning of integrin alpha subunit from the sponge Geodia cydonium.}, journal = {Molecular biology and evolution}, volume = {14}, number = {4}, pages = {391-398}, doi = {10.1093/oxfordjournals.molbev.a025775}, pmid = {9100369}, issn = {0737-4038}, mesh = {Animals ; Base Sequence ; Cloning, Molecular ; DNA, Complementary ; Integrins/chemistry/*genetics ; Membrane Glycoproteins ; Membrane Proteins/*genetics ; Molecular Sequence Data ; Platelet Glycoprotein GPIb-IX Complex ; Porifera/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {Integrins are prominent receptors known from vertebrates and the higher phyla of invertebrates. Until now, no evidence has been provided for the existence of integrins in the lowest Metazoa, the sponges (Porifera). We have isolated and characterized a cDNA clone encoding the alpha subunit of integrin from the marine sponge Geodia cydonium (GCINTEG). The open reading frame encodes a polypeptide of 1,086 residues (118 kDa). The intracellular domain features the sequence Tyr-Phe-x-Gly-Phe-Phe-x-Arg, which is different in one residue from the characteristic consensus pattern for integrin alpha subunits. We conclude that sponges, the oldest multicellular animal phylum, already utilize the structural elements which are required for a tuned and controlled interaction among cells, and between cells and the extracellular matrix.}, } @article {pmid9128171, year = {1997}, author = {Della Santina, CC and Kovacs, GT and Lewis, ER}, title = {Multi-unit recording from regenerated bullfrog eighth nerve using implantable silicon-substrate microelectrodes.}, journal = {Journal of neuroscience methods}, volume = {72}, number = {1}, pages = {71-86}, doi = {10.1016/s0165-0270(96)00159-8}, pmid = {9128171}, issn = {0165-0270}, support = {DC00112-18/DC/NIDCD NIH HHS/United States ; DC01318-02/DC/NIDCD NIH HHS/United States ; GM-08155/GM/NIGMS NIH HHS/United States ; }, mesh = {Acoustic Stimulation ; Action Potentials/physiology ; Animals ; Electrophysiology/*instrumentation/*methods ; Histocytochemistry ; Male ; *Microelectrodes ; Nerve Fibers/physiology ; Nerve Regeneration/physiology ; Rana catesbeiana ; *Silicon ; Vestibulocochlear Nerve/*physiology/surgery ; }, abstract = {Multi-microelectrode silicon devices were developed for extracellular recording from multiple axons in regenerated eighth cranial nerves of American bullfrogs. Each includes a photolithographically defined array of holes and adjacent metal microelectrodes. A device is implanted within a transected eighth nerve; regenerating fibers grow through the holes en route to the brainstem. Multiple spike trains were recorded from two animals at up to 21 weeks after implantation. Single units were tracked for over 8 h. Some responded to sound with tuning typical of fibers innervating the amphibian and basilar papillae. Units of vestibular origin also were recorded. Action potentials were 30-140 microV P-P amid noise of 5 10 microV RMS, an adequate signal-to-noise ratio for spike detection and sorting. Histology confirmed that bundles of myelinated fibers grew through holes near electrodes that recorded activity. The implantation success rate was low, due to surgical morbidity, device extrusion, and lack of nerve regeneration through some devices. Future designs will address these issues and incorporate transistor amplifiers on devices to increase signal-to-noise ratios. The potential of implanted silicon devices to simultaneously record from many axons offers an opportunity for multicellular studies of auditor, vestibular and seismic signal processing in the vertebrate inner ear.}, } @article {pmid9147129, year = {1997}, author = {Ramponi, G and Stefani, M}, title = {Structural, catalytic, and functional properties of low M(r), phosphotyrosine protein phosphatases. Evidence of a long evolutionary history.}, journal = {The international journal of biochemistry & cell biology}, volume = {29}, number = {2}, pages = {279-292}, doi = {10.1016/s1357-2725(96)00109-4}, pmid = {9147129}, issn = {1357-2725}, mesh = {Amino Acid Sequence ; Animals ; Cattle ; Evolution, Molecular ; Humans ; Molecular Sequence Data ; *Protein Tyrosine Phosphatases/chemistry/genetics/metabolism ; }, abstract = {The PTPase family comprises a number of classes of functionally and structurally unrelated enzymes; it represents an important component of the protein-tyrosine phosphorylation/dephosphorylation machinery, which regulates the level of tyrosine phosphorylation of a number of intracellular proteins. A wealth of recently reported data indicates growing interest in a group of PTPases characterized by low (near 20 kDa) molecular weight and high sequence homology (low M(r), PTPases). These enzymes are present in organisms spanning the philogenetic scale, from prokaryotes to yeast and mammals. The sequence homology of the low M(r), PTPases with other classes of PTPases is limited to the active site sequence CXXXXXRS/T, containing the Cys and Arg residues involved in enzyme catalysis found in all PTPases. The X-ray structural data of three enzymes belonging to different classes of PTPases, a bovine liver low M(r), PTPase isoenzyme, PTP1B, and Yersinia PTPase, show that all these enzymes maintain the same active site and overall catalytic mechanism, though displaying different chain foldings and topologies, supporting convergent evolution. Limited findings on the in vivo function of the low M(r), PTPases are presently available; however, an involvement of the mammalian enzymes in the membrane growth factor receptor signal transduction is emerging. The distribution of these enzymes in philogenetically distant unicellular and multicellular organisms supports their participation in important cell functions.}, } @article {pmid9058848, year = {1997}, author = {Starmer, CF}, title = {The cardiac vulnerable period and reentrant arrhythmias: targets of anti- and proarrhythmic processes.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {20}, number = {2 Pt 2}, pages = {445-454}, doi = {10.1111/j.1540-8159.1997.tb06203.x}, pmid = {9058848}, issn = {0147-8389}, support = {HL 32994/HL/NHLBI NIH HHS/United States ; }, mesh = {Action Potentials/drug effects/physiology ; Arrhythmias, Cardiac/drug therapy/*physiopathology ; Cardiomyopathies/physiopathology ; Heart Conduction System/drug effects/physiopathology ; Long QT Syndrome/drug therapy ; Models, Cardiovascular ; Potassium Channels/drug effects/metabolism ; Sodium Channels/drug effects/metabolism ; Tachycardia/drug therapy/physiopathology ; Time Factors ; }, abstract = {Because sudden cardiac death is usually preceded by a reentrant arrhythmia, the precipitating arrhythmia must be multicellular in origin. Therefore clinicians seeking to reduce the incidence of reentrant arrhythmias in their patients with antiarrhythmic drugs that alter propagation may reasonably question the applicability of drug classification schemes (e.g. Sicilian Gambit) that are based on measurements in single cells. This raises a major question: are measures of a drug's anti- and proarrhythmic potential in single cells predictive of its anti- and proarrhythmic properties in tissue? The problem is as follows. From single cell measurements, one expects Class I drugs to reduce excitability, thereby attenuating the occurrence of PVCs. Similarly, one expects Class III drugs to prolong refractoriness and reduce the occurrence of PVCs. We have found in simple models of cardiac tissue that sodium channel blockade (the target of Class I drugs) extends the vulnerable period of a propagating excitation wave, whereas potassium channel blockade (the target of Class III drugs) destabilizes the reentrant path in a manner that amplifies the likelihood of polymorphic tachyarrhythmias. Using analytical, numerical, and experimental studies, we determined that sodium channel blockade was proarrhythmic. In fact, we found that any intervention that slowed conduction was proarrhythmic because slowed conduction increases the vulnerable period and reduces the spatial requirements for sustained reentry. We also found that when obstacles were placed in the path of a propagating wave, reentry occurred when the conduction velocity was less than a critical value. Once reentry was established, we observed that the ECG displayed monomorphic QRS complexes when the reentrant path did not vary from cycle to cycle. Moreover, when the reentry path did vary from cycle to cycle, the ECG displayed polymorphic QRS complexes. The cycle-to-cycle variation in QRS morphology was caused by the spatial variability of the reentry path. The variability of reentry paths (and hence the degree of polymorphic variation in QRS complexes) was amplified by Class III agents. The results presented here show that multicellular proarrhythmic effects are derived from the same mechanisms that exhibit antiarrhythmic properties in single cells.}, } @article {pmid9368287, year = {1997}, author = {Trosko, JE and Inoue, T}, title = {Oxidative stress, signal transduction, and intercellular communication in radiation carcinogenesis.}, journal = {Stem cells (Dayton, Ohio)}, volume = {15 Suppl 2}, number = {}, pages = {59-67}, doi = {10.1002/stem.5530150710}, pmid = {9368287}, issn = {1066-5099}, support = {CA 21104/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Cell Communication ; Cell Differentiation ; Cell Division ; Connexins/biosynthesis ; Gap Junctions/physiology ; Homeostasis ; Humans ; Life Expectancy ; Neoplasms, Radiation-Induced/*physiopathology ; *Oxidative Stress ; *Signal Transduction ; }, abstract = {During the evolution of multicellular organisms, survival in an aerobic environment came about by adaptive responses, both to the endogenous oxidative metabolism within the cells of the organism as well as the chemicals and low-level radiation to which they are exposed. In addition to defense mechanisms shared with single-cell organisms, multicellular organisms are equipped with gap junctions which allow electrotonic and/or metabolic synchronization of processes between coupled cells. The connexin genes, which code for the proteins comprising the gap junctions, provide homeostatic regulation of cell proliferation, differentiation, and adaptive responses of individual cells through a mechanism of "gap junctional intercellular communication." The biological consequences of the response of a multicellular organism to low-level radiation exceeding the background level of oxidative damage to a cell in a tissue could be apoptosis, cell proliferation, or cell differentiation.}, } @article {pmid9347220, year = {1997}, author = {Hochman, A}, title = {Programmed cell death in prokaryotes.}, journal = {Critical reviews in microbiology}, volume = {23}, number = {3}, pages = {207-214}, doi = {10.3109/10408419709115136}, pmid = {9347220}, issn = {1040-841X}, mesh = {*Apoptosis ; Bacteria/*cytology ; }, abstract = {Programmed cell death (PCD), also referred to as apoptosis, is a cellular "suicide" mechanism, based on information from its own internal metabolism, environment, developmental history, and genome. This system was described in eukaryotes continuously along evolution, through amoebae, nematodes, insects, and animals. PCD is essential for the proper development or function of a cell system, organ, or survival of the organism as a whole. Research in the last 2 decades has shown that the life cycle of several prokaryotic organisms display developmental programs, similar to metazoan differentiation, that is part of their adaptation to stressful environments. These include warmer cell formation and differentiation in Caulobacter cereus, sporulation in Bacillus and Streptomyces, heterocyst formation in Anabaena, development of bacteroids in Rhizobium, the formation of multicellular fruiting bodies and sporulation in Myxobacteria, and the formation of nonculturable, but viable, cells in various Gram-negative bacteria. Moreover, and more significantly, the photosynthetic bacteria Rhodobacter capsulatus were shown to release nucleoprotein particles designated "gene transfer agent (GTA)" as they enter the stationary phase. GTAs contain DNA of 3.6 x 10(6) molecular weight, representing all parts of the genome, and they may be taken up by other strains of R. capsulatus, and complement mutants. We postulate that these various modes of stress adaptations in bacteria are prokaryotic manifestation, and possibly the phylogenetic precursor, of the eukaryotic phenomenon, programmed cell death, and therefore we propose to designate it "proapoptosis". In addition to their function, apoptosis and proapoptosis share various mechanistic programmed features, including DNA fragmentation and packaging, cell shrinkage, degradation of RNA, proteolysis and synthesis of new proteins, and the involvement of reactive oxygen species.}, } @article {pmid9203357, year = {1997}, author = {Baluska, F and Volkmann, D and Barlow, PW}, title = {Nuclear components with microtubule-organizing properties in multicellular eukaryotes: functional and evolutionary considerations.}, journal = {International review of cytology}, volume = {175}, number = {}, pages = {91-135}, doi = {10.1016/s0074-7696(08)62126-9}, pmid = {9203357}, issn = {0074-7696}, mesh = {Animals ; Cell Nucleus/*physiology/ultrastructure ; Centrosome/*physiology/ultrastructure ; Eukaryotic Cells/*physiology/ultrastructure ; *Evolution, Molecular ; Microtubules/*physiology/ultrastructure ; Plant Cells ; Spindle Apparatus/*physiology/ultrastructure ; }, abstract = {The nucleus and the microtubular cytoskeleton of eukaryotic cells appear to be structurally and functionally interrelated. Together they constitute a "cell body". One of the most important components of this body is a primary microtubule-organizing center (MTOC-I) located on or near the nuclear surface and composed of material that, in addition to constitutive centrosomal material, also comprises some nuclear matrix components. The MTOC-I shares a continuity with the mitotic spindle and, in animal cells, with the centrosome also. Secondary microtubule-organizing centers (MTOC-IIs) are a special feature of walled plant cells and are found at the plasma membrane where they organize arrays of cortical MTs that are essential for ordered cell wall synthesis and hence for cellular morphogenesis. MTOC-IIs are held to be similar in origin to the MTOC-I, but their material has been translocated to the cell periphery, perhaps by MTs organized and radiating from the MTOC-I. Many intranuclear, matrix-related components have been identified to participate in MT organization during mitosis and cytokinesis; some of them also seem to be related to the condensation and decondensation of chromatin during the mitotic chromosome cycle.}, } @article {pmid9067775, year = {1997}, author = {Bodey, B and Kaiser, HE}, title = {Development of Hassall's bodies of the thymus in humans and other vertebrates (especially mammals) under physiological and pathological conditions: immunocytochemical, electronmicroscopic and in vitro observations.}, journal = {In vivo (Athens, Greece)}, volume = {11}, number = {1}, pages = {61-85}, pmid = {9067775}, issn = {0258-851X}, mesh = {Animals ; Dogs ; Fetus/physiology/physiopathology/ultrastructure ; Humans ; Immunohistochemistry ; Mammals ; Microscopy, Electron ; Thymus Gland/*embryology/physiopathology/*ultrastructure ; }, abstract = {The histogenesis and cell structure progression of Hassall's bodies (HB) was observed employing light and electronmicroscopic histochemical methods in 212 human and 100 dog fetuses at various stages of ontogenesis. Several human pre- and postnatal thymuses were investigated immunohistochemically, employing a library of over 50 poly- and monoclonal antibodies, seeking to determine the cell origin of HBs. The organization of optimal microenvironmental conditions in the thymus requires the added participation of the neural crest. Spontaneous or experimental ablation of the neural crest during early ontogenesis results in abnormal thymic organogenesis. The reticulo-epithelial (RE) cells of 25 postnatal thymuses were also observed under various tissue culture conditions. The development of the first HB was detected on the 38th day of gestation in dogs and during the second part of the third intrauterine lunar month in human fetuses. The greatest developmental progression and main cell-tissue organization of the HBs was observed between 45 and 54 days of gestation in dogs and between 6 and 10 lunar months in humans. During thymic ontogenesis, the HBs appear when lymphopoiesis is already established and the cortex, medulla and the cortico-medullary junction are capable of conducting the positive and negative selection of T lymphocytes undergoing progressive maturation. The HBs are structurally organized from medullary RE cells, which usually undergo hypertrophy prior to their inclusion in the outer cell layer of the corpuscles. The cellular microenvironment of the thymic medulla is composed of networks of cell types, of a variety of origins, and all of them may participate in the construction of growing, progressive HBs. Histochemically, we detected a rich content of basic non-histone proteins, PAS positive substance (glycogen and acid mucopolysaccharides within the bodies. Employing the histological stain of Pasini and immunocytochemical methods with monoclonal antidodies (MoABs) AE2 and AE3, high molecular weight (56.5 to 67 kD) basic keratins were defined in human HBs. Employing a panel of MoABs developed against epithelial cell surface antigens (provided kindly by Dr. Haynes), we observed immunoreactivity localized to the outer cell layer of the HBs with MoABs TE8, TE16 and TE19, while the centrally located cells reacted positively with TE15 and TE19. Immunoreactivity employing the TE8, TE16 and TE19 MoABs was also observed in the epidermal granulosa cell layer, while TE15 reacted with cells of the stratum corneum. The presence of endocrine, peptide secreting RE cells within the HBs was defined with the use of MoAB A2B5, which binds to the GQ ganglioside. The hypertrophied, physiologically active RE cells of the peripheral cell layer of the HBs reacted positively with medium to strong intensity when stained with MoABs UJ127.11, J1153, A2B5, 215.D11, and 275.G7. These results further suggest that HBs are not exclusively degenerative structures. Our transmission electronmicroscopical (TEM) studies on HBs determined the existence of groups of RE cells connected to one another by desmosomes. We also observed long cytoplasmic processes originating from medullary RE cells and directly contacting thymic T lymphocytes and accessory antigen presenting cells (macrophages, dendritic cells, interdigitating cells, Langerhans cells, etc.) by the use of scanning electronmicroscopy (SEM). During our observations on human thymic organ and tissue cultures, no development of HBs could be registered. It is possible that additional cell to cell interactions with cells of different derivations may be necessary for the development of HBs. Thus, our results indicate that the HBs are unique, antigenically distinct, functionally active, multicellular components of the nonlymphocytic, cellular microenvironment of the thymic medulla, and participate in the physiological activities of the prenatal and adult thymus.(ABSTRACT TRUNCATED)}, } @article {pmid9049991, year = {1997}, author = {Chigira, M}, title = {Transplantation and chimera as extended self.}, journal = {Medical hypotheses}, volume = {48}, number = {1}, pages = {63-69}, doi = {10.1016/s0306-9877(97)90025-6}, pmid = {9049991}, issn = {0306-9877}, mesh = {Animals ; Bone Marrow Transplantation/immunology ; DNA ; Humans ; Models, Biological ; Symbiosis ; *Transplantation ; Transplantation Chimera/*immunology ; *Transplantation Immunology ; Transplantation, Heterologous ; Transplantation, Homologous ; }, abstract = {Transplantation can be considered as an artificial reconstitution of symbiosis called chimera, since the donor and recipient carry different DNAs. In successful transplantation, engrafted tissues and cells should be recognized as self by the immune system, as shown in external pathogens. The external milieu introduced by transplantation and infection can only be immunologically recognized as self when it forms a symbiotic relationship with somatic cell society. Immunological identity is a posteriori educated recognizing immunological self and genetic self may be ignored in self-recognition. For example, transplanted bone marrow immunocytes recognize somatic cell society which is selected previously by other immunological standards as self. Dissociation between genetic self and immunological self originates in the development and differentiation of multicellular organisms a priori, since alteration of DNA sequences is necessary in the development and differentiation of multicellular organisms and symbiosis is the essential nature of it.}, } @article {pmid8987773, year = {1997}, author = {Colasanti, M and Venturini, G and Merante, A and Musci, G and Lauro, GM}, title = {Nitric oxide involvement in Hydra vulgaris very primitive olfactory-like system.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {17}, number = {1}, pages = {493-499}, pmid = {8987773}, issn = {0270-6474}, mesh = {Animals ; Calcium/physiology ; Calmodulin/physiology ; Cyclic GMP/physiology ; Electron Spin Resonance Spectroscopy ; Enzyme Inhibitors/pharmacology ; Feeding Behavior/drug effects ; Hydra/*physiology ; Molsidomine/analogs & derivatives/pharmacology ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide/antagonists & inhibitors/*physiology ; Nitric Oxide Synthase/antagonists & inhibitors/metabolism ; Nitrites/metabolism ; Nitroprusside/pharmacology ; Olfactory Pathways/*physiology ; }, abstract = {Hydra feeding response is a very primitive olfactory-like behavior present in a multicellular organism. We investigated the role of nitric oxide (NO) in the induction and control of hydra feeding response. Under basal conditions, hydra specimens produce detectable amounts of nitrite (NO2-), the breakdown product of NO. When hydra were incubated with reduced glutathione (GSH), the typical activator of feeding response, an increase of basal NO production was observed. This effect was inhibited by glutamic or alpha-aminoadipic acids, two GSH antagonists, which block GSH-induced feeding response, and by the NO synthase (NOS) inhibitor L-NAME. Moreover, we found that hydra possess a calcium-dependent (but calmodulin-independent) NOS isoform. By using exogenous NO donors and NOS inhibitors, we demonstrated that NO stimulus can participate both in triggering tentacular movements and in recruiting neighbor tentacles during hydra feeding response. By using dbt2-cGMP, an analog to cGMP, we observed that the NO effect was independent of cGMP pathway. Our results strongly implicate NO involvement in hydra very primitive feeding behavior, thus confirming its preservation throughout evolution.}, } @article {pmid9107136, year = {1996}, author = {Wakahara, M}, title = {Heterochrony and neotenic salamanders: possible clues for understanding the animal development and evolution.}, journal = {Zoological science}, volume = {13}, number = {6}, pages = {765-776}, doi = {10.2108/zsj.13.765}, pmid = {9107136}, issn = {0289-0003}, mesh = {Animals ; *Biological Evolution ; Gene Expression Regulation, Developmental ; Models, Genetic ; Urodela/*genetics/growth & development ; }, abstract = {A synthesis of developmental genetics with evolutionary genetics is now making possible to understand significant evolutionary changes in multicellular organisms. The key concept for unifying the two must be heterochrony. Heterochrony causes evolutionary modifications due to changes in timing and/or rate of development. The heterochrony is conventionally categorized into three patterns as neoteny (retardation in somatic development), progenesis (acceleration in gonadal development), and direct development (acceleration in somatic development, resulting in lack of larval or tadpole stages). A lot of species showing neoteny are known in urodeles, but not in anurans. Neotenic urodeles are also divided into three categories; permanent or obligate, "inducible" obligate and facultative neotenies. Hynobius retardatus, a specific population of which had been reported to show neoteny but is believed to be extinct at present, has become to be used for experimental analysis of heterochronic expression of several adult characters during its ontogeny. Gonadal maturation and a transition of globin subunits from larval to adult types have been shown to occur independently on the morphological metamorphosis in H. retardatus. Mechanisms underlying the heterochrony, including morphogenetic clock, heterochronic genes in Drosophila and C. elegans, temporal colinearity in Hox gene complex in mice, and atavistic transformation induced by altered expression of Hox genes are discussed in terms of current molecular biology.}, } @article {pmid8995053, year = {1996}, author = {Marinets, A and Müller, M and Johnson, PJ and Kulda, J and Scheiner, O and Wiedermann, G and Duchêne, M}, title = {The sequence and organization of the core histone H3 and H4 genes in the early branching amitochondriate protist Trichomonas vaginalis.}, journal = {Journal of molecular evolution}, volume = {43}, number = {6}, pages = {563-571}, pmid = {8995053}, issn = {0022-2844}, support = {AI11942/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Southern ; Cloning, Molecular ; DNA, Complementary/genetics ; Genome ; Histones/*genetics/physiology ; Molecular Sequence Data ; *Phylogeny ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Trichomonas vaginalis/*genetics/physiology ; }, abstract = {Among the unicellular protists, several of which are parasitic, some of the most divergent eukaryotic species are found. The evolutionary distances between protists are so large that even slowly evolving proteins like histones are strongly divergent. In this study we isolated cDNA and genomic histone H3 and H4 clones from Trichomonas vaginalis. Two histone H3 and three histone H4 genes were detected on three genomic clones with one complete H3 and two complete H4 sequences. H3 and H4 genes were divergently transcribed with very short intergenic regions of only 194 bp, which contained T. vaginalis-specific as well as histone-specific putative promoter elements. Southern blot analysis showed that there may be several more histone gene pairs. The two complete histone H4 genes were different on the nucleotide level but encoded the same amino acid sequence. Comparison of the amino acid sequences of the T. vaginalis H3 and H4 histones with sequences from animals, fungi, and plants as well as other protists revealed a significant divergence not only from the sequences in multicellular organisms but especially from the sequences in other protists like Entamoeba histolytica, Trypanosoma cruzi, and Leishmania infantum.}, } @article {pmid9119208, year = {1996}, author = {Altukhov, IuP and Korochkin, LI and Rychkov, IuG}, title = {[Hereditary biochemical diversity in the processes of evolution and individual development].}, journal = {Genetika}, volume = {32}, number = {11}, pages = {1450-1473}, pmid = {9119208}, issn = {0016-6758}, mesh = {Adaptation, Physiological/*genetics ; Animals ; *Biological Evolution ; Gene Expression Regulation, Developmental/*physiology ; *Genetic Variation ; Genome ; Heterozygote ; Humans ; Polymorphism, Genetic ; }, abstract = {Results of long-term studies of Russian authors on regularities of expression of hereditary biochemical diversity in evolution and development are reviewed. Primary attention is given to the concepts of genetic monomorphism and genetic stability of population systems, principles of adaptive gene pool structure and optimum genetic diversity, historical and conservation genetics, the concept of the multilevel gene expression, and temporal regulation of ontogenetic functioning of gene clusters coding for enzymes. A universal genetic approach to the problems of evolution and ontogeny is proposed. A population is regarded as a superorganism whose key property is the hierarchic structure of its genetic stability from the stability of monomorphic genes via stability of polymorphic gene frequencies in a multilevel population system to the stability of the total amount of gene diversity in this system. A multicellular organism is also regarded as a developing hierarchical system of populations of cells and genes interacting in a nonrandom fashion. This maintains stability of metabolic processes and is expressed in consistent correlations between monogenic and polygenic morphophysiological characters. Properties of both organisms are determined by the adaptive heterozygosity optimum, the disturbance of which has negative consequences for both individuals and populations. On the basis of these results and the concept on the common nature of evolutionary and ontogenetic processes, the following conclusions are drawn: genetic processes can be either favorable or adverse for developing organisms and populations; the state of genetic processes can be determined by analysis of gene diversity and their deviations from the optimum, taking into account the adaptive gene pool structure; and negative hazardous consequences of extreme external effects at both the individual and population levels can be detected by methods of biochemical genetics in specially planned monitoring programs. Knowledge of normal processes of realization of hereditary information in evolution of populations and in ontogeny opens up new perspectives in detection of unfavorable processes and their correction. This approach proved promising both for preventive and clinical medicine and for exploitation and artificial reproduction of biological resources.}, } @article {pmid8980520, year = {1996}, author = {Vogel, H and Fischer, S and Valentin, K}, title = {A model for the evolution of the plastid sec apparatus inferred from secY gene phylogeny.}, journal = {Plant molecular biology}, volume = {32}, number = {4}, pages = {685-692}, pmid = {8980520}, issn = {0167-4412}, mesh = {Cloning, Molecular ; *Evolution, Molecular ; Gene Expression Regulation ; Genes/*genetics ; Models, Genetic ; Molecular Sequence Data ; Phylogeny ; Plant Proteins/*genetics ; Plastids/*genetics ; RNA, Messenger/analysis ; Rhodophyta/*genetics ; SEC Translocation Channels ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; }, abstract = {Plastids possess a bacteria-like sec apparatus that is involved in protein import into the thylakoid lumen. We have analyzed one of the genes essential for this process, secY. A secY gene from the unicellular red alga Cyanidium caldarium was found to be transcriptionally active, demonstrating for the first time that secY is functional in a plastid. Unlike the situation seen in bacteria the C. caldarium gene is transcribed monocistronically, despite the fact that it is part of a large ribosomal gene cluster that resembles bacterial spc operons. A molecular phylogeny is presented for 8 plastid-encoded secY genes, four of which have not been published yet. In this analysis plastid secY genes fall into two classes. One of these, comprising of genes from multicellular red algae and Cryptophyta, clusters in a neighbour-joining tree with a cyanobacterial counterpart. Separated from the aforesaid are secY genes from Chromophyta, Glaucocystophyta and a unicellular red alga. All plastid and cyanobacterial sequences are located on the same branch, separated from bacterial homologues. We postulate that the two classes of secY genes are paralogous, i.e. their gene products are involved in different protein translocation processes. Based on this assumption a model for the evolution of the plastid sec apparatus is presented.}, } @article {pmid8896370, year = {1996}, author = {Hanelt, B and Van Schyndel, D and Adema, CM and Lewis, LA and Loker, ES}, title = {The phylogenetic position of Rhopalura ophiocomae (Orthonectida) based on 18S ribosomal DNA sequence analysis.}, journal = {Molecular biology and evolution}, volume = {13}, number = {9}, pages = {1187-1191}, doi = {10.1093/oxfordjournals.molbev.a025683}, pmid = {8896370}, issn = {0737-4038}, mesh = {Animals ; *DNA, Ribosomal ; Eukaryota/classification/genetics ; Female ; Helminths/classification/genetics/physiology ; Invertebrates/classification/genetics ; Models, Genetic ; Parasites/*classification/*genetics/physiology ; *Phylogeny ; Platyhelminths/classification/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {The Orthonectida is a small, poorly known phylum of parasites of marine invertebrates. Their phylogenetic placement is obscure; they have been considered to be multicellular protozoans, primitive animals at a "mesozoan" grade of organization, or secondarily simplified flatworm-like organisms. The best known species in the phylum, Rhopalura ophiocomae, was collected on San Juan Island, Wash. and a complete 18S rDNA sequence was obtained. Using the models of minimum evolution and parsimony, phylogenetic analyses were undertaken and the results lend support to the following hypotheses about orthonectids: (1) orthonectids are more closely aligned with triploblastic metazoan taxa than with the protist or diploblastic metazoan taxa considered in this analysis; (2) orthonectids are not derived members of the phylum Platyhelminthes; and (3) orthonectids and rhombozoans are not each other's closest relatives, thus casting further doubt on the validity of the phylum Mesozoa previously used to encompass both groups.}, } @article {pmid8876205, year = {1996}, author = {Ayala, FJ and Barrio, E and Kwiatowski, J}, title = {Molecular clock or erratic evolution? A tale of two genes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {93}, number = {21}, pages = {11729-11734}, pmid = {8876205}, issn = {0027-8424}, support = {GM42397/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans/enzymology/genetics ; Diptera/enzymology/genetics ; Drosophila/classification/enzymology/genetics ; Drosophilidae/classification/enzymology/genetics ; *Evolution, Molecular ; Genetic Variation ; Glycerolphosphate Dehydrogenase/chemistry/*genetics ; Humans ; Mice ; Molecular Sequence Data ; *Phylogeny ; Rabbits ; Saccharomyces cerevisiae/enzymology/genetics ; Schizosaccharomyces/enzymology/genetics ; Sequence Homology, Amino Acid ; Superoxide Dismutase/chemistry/*genetics ; *Time ; }, abstract = {We have investigated the evolution of glycerol-3-phosphate dehydrogenase (Gpdh). The rate of amino acid replacements is 1 x 10(-10)/site/year when Drosophila species are compared. The rate is 2.7 times greater when Drosophila and Chymomyza species are compared; and about 5 times greater when any of those species are compared with the medfly Ceratitis capitata. This rate of 5 x 10(-10)/site/year is also the rate observed in comparisons between mammals, or between different animal phyla, or between the three multicellular kingdoms. We have also studied the evolution of Cu,Zn superoxide dismutase (Sod). The rate of amino acid replacements is about 17 x 10(-10)/site/year when comparisons are made between dipterans or between mammals, but only 5 x 10(-10) when animal phyla are compared, and only 3 x 10(-10) when the multicellular kingdoms are compared. The apparent decrease by about a factor of 5 in the rate of SOD evolution as the divergence between species increases can be consistent with the molecular clock hypothesis by assuming the covarion hypothesis (namely, that the number of amino acids that can change is constant, but the set of such amino acids changes from time to time and from lineage to lineage). However, we know of no model consistent with the molecular clock hypothesis that would account for the increase in the rate of GPDH evolution as the divergence between species increases.}, } @article {pmid8943509, year = {1996}, author = {Van der Elst, J and Van den Abbeel, E and Camus, M and Smitz, J and Devroey, P and Van Steirteghem, A}, title = {Long-term evaluation of implantation of fresh and cryopreserved human embryos following ovarian stimulation with buserelin acetate-human menopausal gonadotrophin (HMG) or clomiphene citrate-HMG.}, journal = {Human reproduction (Oxford, England)}, volume = {11}, number = {10}, pages = {2097-2106}, doi = {10.1093/oxfordjournals.humrep.a019056}, pmid = {8943509}, issn = {0268-1161}, mesh = {Adult ; Buserelin/*therapeutic use ; Clomiphene/*therapeutic use ; Cohort Studies ; *Cryopreservation ; Drug Combinations ; *Embryo Implantation ; Embryo Transfer ; Embryo, Mammalian ; Evaluation Studies as Topic ; Female ; Fertility Agents, Female/*therapeutic use ; Fertilization in Vitro ; Humans ; Longitudinal Studies ; Menotropins/*therapeutic use ; Ovary/*drug effects ; Pregnancy ; Pregnancy Rate ; }, abstract = {This study is a long-term evaluation of the total pregnancy potential of cohorts of fresh and cryopreserved sibling embryos from in-vitro fertilization (IVF) cycles stimulated with either the gonadotrophin-releasing hormone analogue buserelin (BUS) (long protocol) or clomiphene citrate (CC) both in combination with human menopausal gonadotrophin (HMG). Therefore a retrospective analysis was performed on patients who entered the IVF programme between January 1986 and July 1987 and who had triple embryo transfer in the collection cycle. Significantly more fertilized oocytes developed to good-quality embryos in the CC-HMG group (86.1%) than in the BUS-HMG group (80.8%). Transfer of the three morphologically best-looking embryos was performed in day 2 post-insemination in 106 CC-HMG and 80 BUS-HMG cycles. Supernumerary embryos were cultured for a further 24 h and multicellular embryos with up to 20% of fragments were frozen slowly with 1.5 M dimethylsulphoxide on day 3 post-insemination (162 embryos in CC-HMG cycles, 102 embryos in BUS- HMG cycles). Outcome was measured by embryo survival rate, embryo implantation rate and delivery rate in fresh and frozen embryo transfers. Delivery rates were 31.3 and 21.7% per fresh embryo transfer in BUS-HMG and CC- HMG cycles respectively. Fresh embryo implantation rates were significantly higher in collection cycles stimulated with BUS-HMG (17.9%) than in cycles stimulated with CC-HMG (11.3%). Implantation rates were significantly enhanced in embryos transferred in excess of one in cycles leading to pregnancy, perhaps indicative of higher embryo quality in BUS-HMG cycles. Almost all cryopreserved embryos have by now been thawed, so the contribution of frozen embryos to overall pregnancy rates can be evaluated. Overall morphological survival rates of frozen-thawed embryos have by now been thawed, so the contribution of frozen embryos to overall pregnancy rates can be evaluated Overall morphological survival rates of frozen-thawed embryos were similar for 140 embryos from CC-HMG cycles (50%) and 100 embryos from BUS-HMG cycles (46%). The percentage of fully intact embryos was, however, significantly lower in the BUS-HMG group (19%) than in the CC-HMG group (39.5%). Delivery rates were significantly lower following 30 transfers of frozen-thawed embryos from BUS-HMG-stimulated cycles (3.3%) than following 42 transfers of frozen-thawed embryos from CC-HMG cycles (19.1%). Embryo implantation rates were lower for frozen-thawed embryos from BUS-HMG cycles (2.3%) than from CC-HMG cycles (12.7%). Here we demonstrate that ovarian stimulation with the long protocol BUS-HMG instead of the CC-HMG protocol led to higher embryo implantation rates in collection cycles but to lower intact embryo survival rates and to lower embryo implantation rates for frozen sibling embryos. Despite the lower implantation rates with frozen embryos originating from the BUS-HMG protocol, there was no significant difference between total delivery rate per transfer from cycles stimulated with CC-HMG (30.2%) compared with BUS-HMG (33.8%).}, } @article {pmid8889542, year = {1996}, author = {Mushegian, AR and Koonin, EV}, title = {Sequence analysis of eukaryotic developmental proteins: ancient and novel domains.}, journal = {Genetics}, volume = {144}, number = {2}, pages = {817-828}, pmid = {8889542}, issn = {0016-6731}, mesh = {Amino Acid Sequence ; Animals ; Conserved Sequence ; DNA-Binding Proteins/genetics ; Eukaryotic Cells/metabolism ; Evolution, Molecular ; Molecular Sequence Data ; Proteins/*genetics ; *Sequence Analysis ; Sequence Homology, Amino Acid ; }, abstract = {Most of the genes involved in the development of multicellular eukaryotes encode large, multidomain proteins. To decipher the major trends in the evolution of these proteins and make functional predictions for uncharacterized domains, we applied a strategy of sequence database search that includes construction of specialized data sets and iterative subsequence masking. This computational approach allowed us to detect previously unnoticed but potentially important sequence similarities. Developmental gene products are enriched in predicted nonglobular regions as compared to unbiased sets of eukaryotic and bacterial proteins. Developmental genes that act intracellularly, primarily at the level of transcription regulation, typically code for proteins containing highly conserved DNA-binding domains, most of which appear to have evolved before the radiation of bacteria and eukaryotes. We identified bacterial homologues, namely a protein family that includes the Escherichia coli universal stress protein UspA, for the MADS-box transcription regulators previously described only in eukaryotes. We also show that the FUS6 family of eukaryotic proteins contains a putative DNA-binding domain related to bacterial helix-turn-helix transcription regulators. Developmental proteins that act extracellularly are less conserved and often do not have bacterial homologues. Nevertheless, several provocative similarities between different groups of such proteins were detected.}, } @article {pmid8865666, year = {1996}, author = {Pawlowski, J and Montoya-Burgos, JI and Fahrni, JF and Wüest, J and Zaninetti, L}, title = {Origin of the Mesozoa inferred from 18S rRNA gene sequences.}, journal = {Molecular biology and evolution}, volume = {13}, number = {8}, pages = {1128-1132}, doi = {10.1093/oxfordjournals.molbev.a025675}, pmid = {8865666}, issn = {0737-4038}, mesh = {Animals ; Biological Evolution ; Ciliophora/genetics ; Invertebrates/classification/*physiology ; Male ; Models, Biological ; Models, Genetic ; Molecular Sequence Data ; Nematoda ; Parasites/classification/genetics/physiology ; *Phylogeny ; *RNA, Ribosomal, 18S ; Saccharomyces cerevisiae/genetics ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; }, abstract = {The phylum Mesozoa comprises small, simply organized wormlike parasites of marine invertebrates and is composed of two classes, the Rhombozoa and the Orthonectida. The origin of Mesozoa is uncertain; they are classically considered either as degenerate turbellarians or as primitive multicellular animals related to ciliated protists. In order to precisely determine the phylogenetic position of this group we sequenced the complete 18S rRNA gene of one rhombozoid, Dicyema sp., and one orthonectid, Rhopalura ophiocomae. The sequence analysis shows that the Mesozoa branch early in the animal evolution, closely to nematodes and myxozoans. Our data indicate probably separate origins of rhombozoids and orthonectids, suggesting that their placement in the same phylum needs to be revised.}, } @article {pmid8798342, year = {1996}, author = {Kruse, M and Gamulin, V and Cetkovic, H and Pancer, Z and Müller, IM and Müller, WE}, title = {Molecular evolution of the metazoan protein kinase C multigene family.}, journal = {Journal of molecular evolution}, volume = {43}, number = {4}, pages = {374-383}, pmid = {8798342}, issn = {0022-2844}, support = {RG-33/96-M/RG/CSR NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Catalysis ; *Evolution, Molecular ; Molecular Sequence Data ; Multigene Family/*genetics ; Phylogeny ; Porifera/enzymology/*genetics ; Protein Kinase C/*genetics ; Protein Serine-Threonine Kinases/genetics ; Sequence Homology, Amino Acid ; }, abstract = {Protein kinases C (PKCs) comprise closely related Ser/Thr kinases, ubiquitously present in animal tissues; they respond to second messengers, e.g., Ca2+ and/or diacylglycerol, to express their activities. Two PKCs have been sequenced from Geodia cydonium, a member of the lowest multicellular animals, the sponges (Porifera). One sponge G. cydonium PKC, GCPKC1, belongs to the "novel" (Ca2+-independent) PKC (nPKC) subfamily while the second one, GCPKC2, has the hallmarks of the "conventional" (Ca2+-dependent) PKC (cPKC) subfamily. The alignment of the Ser/Thr catalytic kinase domains, of the predicted aa sequences for these cDNAs with respective segments from previously reported sequences, revealed highest homology to PKCs from animals but also distant relationships to Ser/Thr kinases from protozoa, plants, and bacteria. However, a comparison of the complete structures of the sponge PKCs, which are-already-identical to those of nPKCs and cPKCs from higher metazoa, with the structures of protozoan, plant, and bacterial Ser/Thr kinases indicates that the metazoan PKCs have to be distinguished from the nonmetazoan enzymes. These data indicate that metazoan PKCs have a universal common ancestor which they share with the nonmetazoan Ser/Thr kinases with respect to the kinase domain, but they differ from them in overall structural composition.}, } @article {pmid9035677, year = {1996}, author = {Haas, I and Koldovsky, P}, title = {[Expression of cellular antigen of hypopharyngeal carcinoma in different culture conditions].}, journal = {Laryngo- rhino- otologie}, volume = {75}, number = {9}, pages = {543-547}, doi = {10.1055/s-2007-997630}, pmid = {9035677}, issn = {0935-8943}, mesh = {Adult ; Biomarkers, Tumor/*genetics ; Carcinoma, Squamous Cell/genetics/*pathology ; Cell Division/physiology ; Culture Media ; Epithelium/pathology ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Hypopharyngeal Neoplasms/genetics/*pathology ; Immunoenzyme Techniques ; Male ; Middle Aged ; Spheroids, Cellular/pathology ; Tumor Cells, Cultured/*pathology ; }, abstract = {BACKGROUND: The need to improve therapy regimes, determine prognosis, and study biological properties of tumors extracorporally led to development of different experimental systems. In order to approach the in vivo situation, specific properties of the tumors of origin should be retained by the cells in culture over relatively long periods. However, culture conditions may change expression of cellular antigens.

METHODS: Cryosections of a hypopharyngeal carcinoma were compared in this respect with different cultivation systems (2-dimensional monolayers [ML], 3-dimensional multicellular tumor spheroids [MTS] and substrate cultures on Gelita) in regard to expression of cytokeratins (CK) 1, 7, 10, 14, 18 and 19, vimentin, neurofilament (NF) kD200 and 68, ganglioside GD2, oncogene products (P53 mutant and wild), and membrane-associated antigens (HLA-ABC and -DR, epidermal growth factor receptor EGFR).

RESULTS: Semiquantitative immunohistochemical methods revealed differences in expression of CK1, 14 and 19, GD2, and P53 mutant between these systems.

CONCLUSION: Pronounced expression of markers in MTS compared to original biopsy and monolayer emphasizes the importance of cell-cell contact and 3-dimensionality or metabolic stress. However, weak marker expression within substrate cultures may reflect loose cell-cell contact observed. In these experiments, the antigenic configuration of MTS resembled the one of the original tumor more than the other culture systems: monolayer and growth on substrate. As vimentin and NF are not expressed by healthy epithelial cells of adults, occurrence of intratumoral vimentin and NF could point to derepression of early differentiation antigens.}, } @article {pmid8927690, year = {1996}, author = {Hirabayashi, J}, title = {On the origin of elementary hexoses.}, journal = {The Quarterly review of biology}, volume = {71}, number = {3}, pages = {365-380}, doi = {10.1086/419443}, pmid = {8927690}, issn = {0033-5770}, mesh = {Animals ; Blood Group Antigens/*chemistry ; Carbohydrate Conformation ; Carbohydrate Sequence ; Fructose/chemistry/metabolism ; Galactose/chemistry/metabolism ; Glucose/chemistry/metabolism ; Hexoses/*chemistry/metabolism ; Humans ; Mannose/chemistry/metabolism ; Molecular Sequence Data ; }, abstract = {A possible scenario on the origin of elementary hexoses (fructose, glucose, mannose, and galactose) is proposed: (1) Formol reaction, an autocatalytic polymerization reaction, occurred on the primitive earth under weakly alkaline conditions to generate various small molecular compounds. (2) Among them, glyceraldehyde and dihydroxyacetone undergo aldol condensation to produce stable ketohexoses, fructose and sorbose. (3) Subsequently, Lobry de Bruyn rearrangement converts fructose into stable aldohexoses, glucose, and mannose. (4) Thus, prebiotically synthesized ¿first triplet¿ hexoses would have been available for utilization by ancestral primitive microorganisms. (5) After the development of biochemical pathways, various saccharides, including galactose, were biosynthesized from glucose and mannose as ¿bricolage products¿; the utilization of galactose as a key recognition molecule, based on its distinctive axial 4-OH and its outermost location in glycoconjugates, owing to its late arrival, may have evolved concomitantly with the evolution of multicellular organisms.}, } @article {pmid8892476, year = {1996}, author = {Denekamp, J}, title = {The broad spectrum of preclinical radiobiology: British contributions.}, journal = {International journal of radiation oncology, biology, physics}, volume = {36}, number = {2}, pages = {497-509}, doi = {10.1016/s0360-3016(96)00314-8}, pmid = {8892476}, issn = {0360-3016}, mesh = {History, 20th Century ; Radiobiology/*history ; Research/history ; United Kingdom ; }, abstract = {British radiobiologists have often been at the forefront in taking clinical questions into the laboratory and in taking the results back into the clinic, i.e., what is nowadays labeled as Translational Research. They have published widely and have been very active in lectures, workshops, and discussions, forming an important component of the international communication web, both within the basic science aspects and in the translation from science to medicine, and back again. Major contributions have been made at the cellular and subcellular level, and at the level of multicellular structures, both normal and malignant. The common features of the response of cells to single doses in well-defined conditions have been used to interpret the much greater complexity of tissue and tumor responses treated with repeated small doses in a fractionated course, both of photons and other radiations, with and without chemical modifiers. The many contributions to the field of cell kinetics have provided the tools with which an understanding has been gained of the latency and evolution of radiation damage in different tissues. The prolonged interest in microenvironmental gradients and compensatory responses to injury have provided a framework for designing better radiotherapy schedules, and considerable spin-off to other branches of cancer therapy.}, } @article {pmid8781179, year = {1996}, author = {Choi, G and Przybylska, M and Straus, D}, title = {Three abundant germ line-specific transcripts in Volvox carteri encode photosynthetic proteins.}, journal = {Current genetics}, volume = {30}, number = {4}, pages = {347-355}, doi = {10.1007/s002940050143}, pmid = {8781179}, issn = {0172-8083}, mesh = {*Algal Proteins ; Amino Acid Sequence ; Chlorophyta/*genetics ; Codon ; Enhancer Elements, Genetic ; Ferredoxin-NADP Reductase/genetics ; Fungal Proteins/*genetics ; Gene Expression Regulation ; Germ Cells/*chemistry ; Models, Biological ; Molecular Sequence Data ; Photosynthesis/*genetics ; Photosynthetic Reaction Center Complex Proteins/genetics ; Plant Proteins/genetics ; Protein Biosynthesis ; RNA, Messenger/genetics ; Sequence Homology, Amino Acid ; *Transcription, Genetic ; }, abstract = {Volvox carteri is a multicellular eukaryotic green alga composed of about 2000 cells of only two differentiated types: somatic and germ line. To understand how embryonic cells are assigned either to somatic or germ line fates, we are investigating the regulation of transcripts that are abundant in only one cell type. Here we report the identity of three transcripts that are coordinately expressed at high levels in germ line cells but not in somatic cells. Surprisingly, all three transcripts encode photosynthetic chloroplast proteins (light-harvesting complex protein, oxygen-evolving enhancer protein 3, and ferredoxin-NADP+ reductase) that are transcribed from nuclear genes. We discuss why these mRNAs might be required at high levels in germ line cells and present a hypothesis, suggested by our results, on the evolution of cell specialization in the Volvocales.}, } @article {pmid8703085, year = {1996}, author = {Waterborg, JH and Robertson, AJ}, title = {Common features of analogous replacement histone H3 genes in animals and plants.}, journal = {Journal of molecular evolution}, volume = {43}, number = {3}, pages = {194-206}, pmid = {8703085}, issn = {0022-2844}, mesh = {Amino Acid Sequence ; Animals ; Databases, Factual ; *Evolution, Molecular ; *Genes ; *Genes, Plant ; Histones/*genetics ; Humans ; Introns ; Invertebrates ; Mammals ; Molecular Sequence Data ; *Phylogeny ; RNA, Messenger/biosynthesis ; Sequence Homology, Amino Acid ; Transcription, Genetic ; }, abstract = {Phylogenetic analysis of histone H3 protein sequences demonstrates the independent origin of the replacement histone H3 genes in animals and in plants. Multiple introns in the replacement histone H3 genes of animals in a pattern distinct from that in plant replacement H3 genes supports this conclusion. It is suggested that replacement H3 genes arose at the same time that, independently, multicellular forms of animals and of plants evolved. Judged by the degree of invariant and functionally constrained amino acid positions, histones H3 and H4, which form together the tetramer kernel of the nucleosome, have co-evolved with equal rates of sequence divergence. Residues 31 and 87 in histone H3 are the only residues that consistently changed across each gene duplication event that created functional replacement histone H3 variant forms. Once changed, these residues have remained invariant across divergent speciation. This suggests that they are required to allow replacement histone H3 to participate in the assembly of nucleosomes in non-S-phase cells. The abundant occurrence of polypyrimidine sequences in the introns of all replacement H3 genes, and the replacement of an intron by a polypyrimidine motif upstream of the alfalfa replacement H3 gene, suggests a function. It is speculated that they may contribute to the characteristic cell-cycle-independent pattern of replacement histone H3 genes by binding nucleosome-excluding proteins.}, } @article {pmid8760489, year = {1996}, author = {Michod, RE}, title = {Cooperation and conflict in the evolution of individuality. II. Conflict mediation.}, journal = {Proceedings. Biological sciences}, volume = {263}, number = {1372}, pages = {813-822}, doi = {10.1098/rspb.1996.0121}, pmid = {8760489}, issn = {0962-8452}, support = {GM-19949/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Conflict, Psychological ; Gene Deletion ; *Genetic Variation ; Genotype ; Humans ; Mathematics ; *Models, Genetic ; Models, Psychological ; Personality ; Recombination, Genetic ; Reproduction ; *Selection, Genetic ; }, abstract = {Evolutionary transitions in the units of selection require the promotion of cooperation and the regulation of conflict among the lower level units. For multicellular organisms to emerge as a new unit of selection, the selfish tendencies of their component cells had to be controlled. Theoretical results indicate organisms may regulate this internal conflict and competition in several ways: by reducing the somatic mutation rate, by sequestering cells in a germ line and by directly reducing the benefits to cell of defecting.}, } @article {pmid8796186, year = {1996}, author = {Lachmann, M and Jablonka, E}, title = {The inheritance of phenotypes: an adaptation to fluctuating environments.}, journal = {Journal of theoretical biology}, volume = {181}, number = {1}, pages = {1-9}, doi = {10.1006/jtbi.1996.0109}, pmid = {8796186}, issn = {0022-5193}, support = {GM 28016/GM/NIGMS NIH HHS/United States ; }, mesh = {*Adaptation, Physiological ; Animals ; *Biological Evolution ; *Environment ; *Models, Genetic ; *Phenotype ; }, abstract = {We discuss simple models for the evolution of rates of spontaneous and induced heritable phenotypic variations in a periodically fluctuating environment with a cycle length between two and 100 generations. For the simplest case, the optimal spontaneous transition rate between two states is approximately 1/n (where n is the cycle length). It is also shown that selection for the optimal transition rate under these conditions is surprisingly strong. When n is small, this means that the heritable variations are produced by non-classical inheritance systems, including non-DNA inheritance systems. Thus, it is predicted that in genes controlling adaptation to such environments, non-classical genetic effects are likely to be observed. We argue that the evolution of spontaneous and induced heritable transitions played an important role in the evolution of ontogenies of both unicellular and multicellular organisms. The existence of a machinery for producing induced heritable phenotypic variations introduces a "Lamarckian" factor into evolution.}, } @article {pmid8682215, year = {1996}, author = {Tamames, J and Ouzounis, C and Sander, C and Valencia, A}, title = {Genomes with distinct function composition.}, journal = {FEBS letters}, volume = {389}, number = {1}, pages = {96-101}, doi = {10.1016/0014-5793(96)00527-3}, pmid = {8682215}, issn = {0014-5793}, mesh = {Animals ; Evolution, Molecular ; Genes, Plant ; *Genome ; Genome, Bacterial ; Genome, Viral ; Humans ; Proteins/classification/genetics/*physiology ; }, abstract = {The functional composition of organisms can be analysed for the first time with the appearance of complete or sizeable parts of various genomes. We have reduced the problem of protein function classification to a simple scheme with three classes of protein function: energy-, information- and communication-associated proteins. Finer classification schemes can be easily mapped to the above three classes. To deal with the vast amount of information, a system for automatic function classification using database annotations has been developed. The system is able to classify correctly about 80% of the query sequences with annotations. Using this system, we can analyse samples from the genomes of the most represented species in sequence databases and compare their genomic composition. The similarities and differences for different taxonomic groups are strikingly intuitive. Viruses have the highest proportion of proteins involved in the control and expression of genetic information. Bacteria have the highest proportion of their genes dedicated to the production of proteins associated with small molecule transformations and transport. Animals have a very large proportion of proteins associated with intra- and intercellular communication and other regulatory processes. In general, the proportion of communication-related proteins increases during evolution, indicating trends that led to the emergence of the eukaryotic cell and later the transition from unicellular to multicellular organisms.}, } @article {pmid8806076, year = {1996}, author = {Suzuki, ST}, title = {Structural and functional diversity of cadherin superfamily: are new members of cadherin superfamily involved in signal transduction pathway?.}, journal = {Journal of cellular biochemistry}, volume = {61}, number = {4}, pages = {531-542}, doi = {10.1002/(sici)1097-4644(19960616)61:4<531::aid-jcb6>3.0.co;2-p}, pmid = {8806076}, issn = {0730-2312}, support = {NS32456/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cadherins/*chemistry/*physiology ; Cell Adhesion/*physiology ; Evolution, Molecular ; Mice ; Signal Transduction/*physiology ; }, abstract = {A large number of cadherins and cadherin-related proteins are expressed in different tissues of a variety of multicellular organisms. These proteins share one property: their extracellular domains consist of multiple repeats of a cadherin-specific motif. A recent structure study has shown that the cadherin repeats roughly corresponding to the folding unit of the extracellular domains. The members of the cadherin superfamily are roughly classified into two groups, classical type cadherins proteins and protocadherin type according to their structural properties. These proteins appear to be derived from a common ancestor that might have cadherin repeats similar to those of the current protocadherins, and to have common functional properties. Among various cadherins, E-cadherin was the first to be identified as a Ca(2+)-dependent homophilic adhesion protein. Recent knockout mice experiments have proven its biological role, but there are still several puzzling unsolved properties of the cell adhesion activity. Other members of cadherin superfamily show divergent properties and many lack some of the expected properties of cell adhesion protein. Since recent studies of various adhesion proteins reveal that they are involved in different signal transduction pathways, the idea that the new members of cadherin superfamily may participate in more general cell-cell interaction processes including signal transduction is an intriguing hypothesis. The cadherin superfamily is structurally divergent and possibly functionally divergent as well.}, } @article {pmid8654977, year = {1996}, author = {Hobmayer, E and Hatta, M and Fischer, R and Fujisawa, T and Holstein, TW and Sugiyama, T}, title = {Identification of a Hydra homologue of the beta-catenin/plakoglobin/armadillo gene family.}, journal = {Gene}, volume = {172}, number = {1}, pages = {155-159}, doi = {10.1016/0378-1119(96)00162-x}, pmid = {8654977}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Animals ; Armadillo Domain Proteins ; Biological Evolution ; Cloning, Molecular ; Cytoskeletal Proteins/*genetics ; DNA, Complementary ; Desmoplakins ; *Drosophila Proteins ; Hydra/*genetics ; Molecular Sequence Data ; *Multigene Family ; Proteins/*genetics ; Sequence Homology, Amino Acid ; *Trans-Activators ; beta Catenin ; gamma Catenin ; }, abstract = {The beta-catenin/plakoglobin/armadillo gene family encodes a group of highly conserved proteins which play important roles in cadherin-mediated cell adhesion and in signal transduction mechanisms involved in regulating development. This gene family previously had been isolated only from higher metazoans. Here, we describe the isolation and characterization of a beta-catenin (beta Ctn) homologue from Hydra magnipapillata, a diploblastic lower metazoan. Comparison of the putative amino acid (aa) sequence of Hydra beta Ctn, with its homologues in higher metazoans, shows that a repeating 42-aa motif present in its central domain is highly conserved throughout the metazoa. This suggests that beta Ctn appeared very early in metazoan evolution, possibly when primitive multicellular animals started to form epithelial cell layers.}, } @article {pmid8724539, year = {1996}, author = {Yin, JA and Jowitt, SN}, title = {Clonality switch in acute myeloid leukemia.}, journal = {Leukemia & lymphoma}, volume = {22}, number = {1-2}, pages = {125-130}, doi = {10.3109/10428199609051739}, pmid = {8724539}, issn = {1042-8194}, mesh = {Adult ; Anemia, Refractory, with Excess of Blasts/*pathology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Blast Crisis/pathology ; Bone Marrow/pathology ; Clone Cells/*pathology ; Cyclophosphamide/administration & dosage ; Cytarabine/administration & dosage ; Daunorubicin/administration & dosage ; Disease Progression ; Dosage Compensation, Genetic ; Female ; Hematopoiesis ; Heterozygote ; Humans ; Leukemia, Myeloid, Acute/drug therapy/*pathology ; Neoplastic Stem Cells/*pathology ; Prednisolone/administration & dosage ; Remission Induction ; Thioguanine/administration & dosage ; Vincristine/administration & dosage ; }, abstract = {We have previously described a case of clonality switch in a female patient with acute myeloid leukemia (AML) by X-chromosome inactivation analysis. She presented with refractory anemia with excess blasts in transformation but soon progressed to overt AML. Following induction chemotherapy, she went into complete remission but later relapsed into a second myelodysplastic phase. Analysis of her X-linked DNA polymorphism patterns at presentation and relapse showed that hematopoiesis was clonal, but the genotypes of the two clones was different. She remains clinically well and has a virtually normal blood count more than 5 years from presentation. We now report an update of this unique case and discuss the implications of this finding within the context of a multicellular origin of leukemia.}, } @article {pmid8615974, year = {1996}, author = {Levin, RJ and Bradley, MK}, title = {Neuroectodermal antigens persist in benign and malignant salivary gland tumor cultures.}, journal = {Archives of otolaryngology--head & neck surgery}, volume = {122}, number = {5}, pages = {551-7; discussion 557-8}, doi = {10.1001/archotol.1996.01890170083015}, pmid = {8615974}, issn = {0886-4470}, mesh = {Antibodies, Monoclonal ; Antigens, Neoplasm/*analysis ; Cell Division ; Glial Fibrillary Acidic Protein/ultrastructure ; Humans ; Immunohistochemistry ; Neuroectodermal Tumors/*immunology ; Salivary Gland Neoplasms/*immunology/pathology/ultrastructure ; Salivary Glands/*immunology/pathology/ultrastructure ; Tumor Cells, Cultured ; }, abstract = {OBJECTIVE: To determine whether a heterogeneous collection of salivary gland tumors shared common antigenic characteristics and growth patterns in tissue culture.

DESIGN: Cell cultures were derived from benign and malignant salivary gland neoplasms, cultured conservatively, and serially analyzed for epithelial, myoepithelial, and neuroectodermal antigens.

SUBJECTS: Nineteen samples reflecting the spectrum of salivary tumor pathologic characteristics were established in tissue culture. Most were derived from benign pleomorphic adenomas, and several were from carcinomas, including carcinoma ex pleomorphic adenoma, and mucoepidermoid and adenoid cystic carcinoma.

RESULTS: All cultures were epithelial as determined by morphologic and antigenic examination, using antibodies for cytokeratin. The phenotype of cells derived from benign tumors, especially the pleomorphic adenomas, resembled those in the original neoplasm. Those from carcinomas were similar, with less differentiated characteristics. Manipulation of growth conditions altered the phenotypes shown in culture. Some cultures contained cells expressing vascular smooth-muscle actin and glial fibrillary acidic protein or nestin.

CONCLUSIONS: This model cell system containing proliferative cells from several tumor types is consistent with a stem-cell theory of salivary gland tumor origin. Our data were not consistent with the bicellular or multicellular theory. We hypothesize a neuroectodermal origin for this group of apparently heterogeneous tumors. These cultured cells will be valuable for in-depth investigation of the loss of proliferation controls in benign and malignant tumors of the salivary gland.}, } @article {pmid8633012, year = {1996}, author = {Heck, SD and Faraci, WS and Kelbaugh, PR and Saccomano, NA and Thadeio, PF and Volkmann, RA}, title = {Posttranslational amino acid epimerization: enzyme-catalyzed isomerization of amino acid residues in peptide chains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {93}, number = {9}, pages = {4036-4039}, pmid = {8633012}, issn = {0027-8424}, mesh = {Amino Acid Isomerases/*metabolism ; Amino Acid Sequence ; Animals ; Anti-Bacterial Agents/biosynthesis ; Binding Sites ; Kinetics ; Molecular Sequence Data ; Mollusca ; Oligopeptides/chemistry/metabolism ; Opioid Peptides ; *Protein Processing, Post-Translational ; Ranidae ; Ribosomes/metabolism ; Serine ; Skin ; Substrate Specificity ; }, abstract = {Since ribosomally mediated protein biosynthesis is confined to the L-amino acid pool, the presence of D-amino acids in peptides was considered for many years to be restricted to proteins of prokaryotic origin. Unicellular microorganisms have been responsible for the generation of a host of D-amino acid-containing peptide antibiotics (gramicidin, actinomycin, bacitracin, polymyxins). Recently, a series of mu and delta opioid receptor agonists [dermorphins and deltorphins] and neuroactive tetrapeptides containing a D-amino acid residue have been isolated from amphibian (frog) skin and mollusks. Amino acid sequences obtained from the cDNA libraries coincide with the observed dermorphin and deltorphin sequences, suggesting a stereospecific posttranslational amino acid isomerization of unknown mechanism. A cofactor-independent serine isomerase found in the venom of the Agelenopsis aperta spider provides the first major clue to explain how multicellular organisms are capable of incorporating single D-amino acid residues into these and other eukaryotic peptides. The enzyme is capable of isomerizing serine, cysteine, O-methylserine, and alanine residues in the middle of peptide chains, thereby providing a biochemical capability that, until now, had not been observed. Both D- and L-amino acid residues are susceptible to isomerization. The substrates share a common Leu-Xaa-Phe-Ala recognition site. Early in the reaction sequence, solvent-derived deuterium resides solely with the epimerized product (not substrate) in isomerizations carried out in 2H2O. Significant deuterium isotope effects are obtained in these reactions in addition to isomerizations of isotopically labeled substrates (2H at the epimerizeable serine alpha-carbon atom). The combined kinetic and structural data suggests a two-base mechanism in which abstraction of a proton from one face is concomitant with delivery from the opposite face by the conjugate acid of the second enzymic base.}, } @article {pmid8621508, year = {1996}, author = {Salgado, A and Silva, AM and Santos, RM and Rosário, LM}, title = {Multiphasic action of glucose and alpha-ketoisocaproic acid on the cytosolic pH of pancreatic beta-cells. Evidence for an acidification pathway linked to the stimulation of Ca2+ influx.}, journal = {The Journal of biological chemistry}, volume = {271}, number = {15}, pages = {8738-8746}, doi = {10.1074/jbc.271.15.8738}, pmid = {8621508}, issn = {0021-9258}, mesh = {Animals ; Calcium/metabolism ; Cells, Cultured ; Cytosol/chemistry ; Female ; Glucose/*metabolism ; *Hydrogen-Ion Concentration ; Islets of Langerhans/*metabolism ; Keto Acids/*metabolism ; Membrane Potentials ; Mice ; Mitochondria/metabolism ; }, abstract = {Glucose stimulation raises the pHi of pancreatic beta-cells, but the underlying mechanisms are not well understood. We have now investigated the acute effects of metabolizable (glucose and the mitochondrial substrate alpha-ketoisocaproic acid, KIC) and nonmetabolizable (high K+ and the K-ATP channel blocker tolbutamide) insulin secretagogues on the pHi of pancreatic beta-cells isolated from normal mice, as assessed by BCECF fluorescence from single cells or islets in the presence of external bicarbonate. The typical acute effect of glucose (22-30 mM) on the pHi was a fast alkalinization of approximately 0.11 unit, followed by a slower acidification. The relative expression of the alkalinizing and acidifying components was variable, with some cells and islets displaying a predominant alkalinization, others a predominant acidification, and others yet a mixed combination of the two. The initial alkalinization preceded the [Ca2+]i rise associated with the activation of voltage-sensitive Ca2+ channels. There was a significant overlap between the glucose-evoked [Ca2+]i rise and the development of the secondary acidification. Depolarization with 30 mM K+ and tolbutamide evoked pronounced [Ca2+]i rises and concomitant cytosolic acidifications. Blocking glucose-induced Ca2+ influx (with 0 Ca2+, nifedipine, or the K-ATP channel agonist diazoxide) suppressed the secondary acidification while having variable effects (potentiation or slight attenuation) on the initial alkalinization. KIC exerted glucose-like effects on the pHi and [Ca2+]i, but the amplitude of the initial alkalinization was about twice as large for KIC relative to glucose. It is concluded that the acute effect of glucose on the pHi of pancreatic beta-cells is biphasic. While the initial cytosolic alkalinization is an immediate consequence of the activation of H+-consuming metabolic steps in the mitochondria, the secondary acidification appears to originate from enhanced Ca2+ turnover in the cytoplasm. The degree of coupling between glucose metabolism and Ca2+ influx as well as the relative efficacies of these processes determines whether the acute pHi response of a beta-cell (or of a tightly coupled multicellular system such as an islet of Langerhans) is predominantly an alkalinization, an acidification, or a mixed proportion of the two.}, } @article {pmid8998973, year = {1996}, author = {Rasmussen, L and Christensen, ST and Schousboe, P and Wheatley, DN}, title = {Cell survival and multiplication. The overriding need for signals: from unicellular to multicellular systems.}, journal = {FEMS microbiology letters}, volume = {137}, number = {2-3}, pages = {123-128}, doi = {10.1016/0378-1097(96)00053-5}, pmid = {8998973}, issn = {0378-1097}, mesh = {Animals ; Cell Division/drug effects/*physiology ; Enzyme Inhibitors/pharmacology ; Escherichia coli/cytology ; Guanylate Cyclase/antagonists & inhibitors/metabolism ; Protein Kinase C/antagonists & inhibitors/metabolism ; Saccharomyces cerevisiae/cytology/drug effects/growth & development ; Signal Transduction/drug effects/*physiology ; Tetrahymena thermophila/cytology/drug effects/growth & development ; }, abstract = {There are clear similarities in the control mechanisms for cell survival and multiplication in the two eukaryotes, the ciliate Tetrahymena thermophila and the yeast, Saccharomyces cerevisiae. Cell multiplication in both organisms is activated by the same compounds (phorbol esters, diacylglycerol, tetrapyrroles, etc.). These compounds also affect cell multiplication and other activities in mammalian cell systems. This homology in control mechanisms in two distinct groups of unicellular eukaryotes on the one hand, and in cells from multicellular animals on the other, leads us to propose that these cytoplasmic control mechanisms for cell survival and multiplication originated in the unicellular eukaryotes.}, } @article {pmid8637856, year = {1996}, author = {Vaux, DL and Strasser, A}, title = {The molecular biology of apoptosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {93}, number = {6}, pages = {2239-2244}, pmid = {8637856}, issn = {0027-8424}, mesh = {Animals ; *Apoptosis ; Caenorhabditis elegans/cytology/enzymology ; Caenorhabditis elegans Proteins ; *Caspases ; Cell Cycle ; Cysteine Endopeptidases/physiology ; Cytotoxins ; Enzyme Activation ; Helminth Proteins/physiology ; Homeostasis ; Humans ; T-Lymphocytes/cytology ; Virus Diseases/pathology ; }, abstract = {All multicellular organisms have mechanisms for killing their own cells, and use physiological cell death for defence, development, homeostasis, and aging. Apoptosis is a morphologically recognizable form of cell death that is implemented by a mechanism that has been conserved throughout evolution from nematode to man. Thus homologs of the genes that implement cell death in nematodes also do so in mammals, but in mammals the process is considerably more complex, involving multiple isoforms of the components of the cell death machinery. In some circumstances this allows independent regulation of pathways that converge upon a common end point. A molecular understanding of this mechanism may allow design of therapies that either enhance or block cell death at will.}, } @article {pmid8867806, year = {1996}, author = {Boulikas, T}, title = {Common structural features of replication origins in all life forms.}, journal = {Journal of cellular biochemistry}, volume = {60}, number = {3}, pages = {297-316}, doi = {10.1002/(sici)1097-4644(19960301)60:3<297::aid-jcb2>3.0.co;2-r}, pmid = {8867806}, issn = {0730-2312}, mesh = {Animals ; Base Composition ; Base Sequence ; DNA/chemistry ; Humans ; Molecular Sequence Data ; Nucleic Acid Conformation ; Repetitive Sequences, Nucleic Acid/genetics ; Replication Origin/*genetics ; Transcription Factors/physiology ; }, abstract = {Origins of replication (ORIs) among prokaryotes, viruses, and multicellular organisms appear to possess simple tri-, tetra-, or higher dispersed repetitions of nucleotides, AT tracts, inverted repeats, one to four binding sites of an initiator protein, intrinsically curved DNA, DNase I-hypersensitive sites, a distinct pattern of DNA methylation, and binding sites for transcription factors. Eukaryotic ORIs are sequestered on the nuclear matrix; this attachment is supposed to facilitate execution of their activation/deactivation programs during development. Furthermore, ORIs fall into various classes with respect to their sequence complexity: those enriched in AT tracts, those with GA- and CT-rich tracts, a smaller class of GC-rich ORIs, and a major class composed of mixed motifs yet containing distinct AT and polypurine or GC stretches. Multimers of an initiator protein in prokaryotes and viruses that might have evolved into a multiprotein replication initiation complex in multicellular organisms bind to the core ORI, causing a structural distortion to the DNA which is transferred to the AT tract flanking the initiator protein site; single-stranded DNA-binding proteins then interact with the melted AT tract as well as with the DNA polymerase alpha-primase complex in animal viruses and mammalian cells, causing initiation in DNA replication. ORIs in mammalian cells seem to colocalize with matrix-attached regions and are proposed to become DNase I-hypersensitive during their activation.}, } @article {pmid8849902, year = {1996}, author = {Kumar, S and Balczarek, KA and Lai, ZC}, title = {Evolution of the hedgehog gene family.}, journal = {Genetics}, volume = {142}, number = {3}, pages = {965-972}, pmid = {8849902}, issn = {0016-6731}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Biological Evolution ; DNA ; *Drosophila Proteins ; Hedgehog Proteins ; Humans ; Molecular Sequence Data ; Phylogeny ; Proteins/chemistry/*genetics ; Sequence Homology, Amino Acid ; *Trans-Activators ; }, abstract = {Effective intercellular communication is an important feature in the development of multicellular organisms. Secreted hedgehog (hh) protein is essential for both long- and short-range cellular signaling required for body pattern formation in animals. In a molecular evolutionary study, we find that the vertebrate homologs of the Drosophila hh gene arose by two gene duplications: the first gave rise to Desert hh, whereas the second produced the Indian and Sonic hh genes. Both duplications occurred before the emergence of vertebrates and probably before the evolution of chordates. The amino-terminal fragment of the hh precursor, crucial in long- and short-range intercellular communication, evolves two to four times slower than the carboxyl-terminal fragment in both Drosophila hh and its vertebrate homologues, suggesting conservation of mechanism of hh action in animals. A majority of amino acid substitutions in the amino- and carboxyl-terminal fragments are conservative, but the carboxyl-terminal domain has undergone extensive insertion-deletion events while maintaining its autocleavage protease activity. Our results point to similarity of evolutionary constraints among sites of Drosophila and vertebrate hh homologs and suggest some future directions for understanding the role of hh genes in the evolution of developmental complexity in animals.}, } @article {pmid8604305, year = {1996}, author = {Cermakian, N and Ikeda, TM and Cedergren, R and Gray, MW}, title = {Sequences homologous to yeast mitochondrial and bacteriophage T3 and T7 RNA polymerases are widespread throughout the eukaryotic lineage.}, journal = {Nucleic acids research}, volume = {24}, number = {4}, pages = {648-654}, pmid = {8604305}, issn = {0305-1048}, mesh = {Amino Acid Sequence ; Animals ; Bacteriophage T3/*enzymology ; Bacteriophage T7/*enzymology ; Base Sequence ; DNA-Directed RNA Polymerases/*genetics ; Mitochondria/enzymology ; Molecular Sequence Data ; Phylogeny ; Saccharomyces cerevisiae/*enzymology ; Sequence Homology, Amino Acid ; }, abstract = {Although mitochondria and chloroplasts are considered to be descendants of eubacteria-like endo- symbionts, the mitochondrial RNA polymerase of yeast is a nucleus-encoded, single-subunit enzyme homologous to bacteriophage T3 and T7 RNA polymerases, rather than a multi-component, eubacterial-type alpha 2 beta beta' enzyme, as encoded in chloroplast DNA. To broaden our knowledge of the mitochondrial transcriptional apparatus, we have used a polymerase chain reaction (PCR) approach designed to amplify an internal portion of phage T3/T7-like RNA polymerase genes. Using this strategy, we have recovered sequences homologous to yeast mitochondrial and phage T3/T7 RNA polymerases from a phylogenetically broad range of multicellular and unicellular eukaryotes. These organisms display diverse patterns of mitochondrial genome organization and expression, and include species that separated from the main eukaryotic line early in the evolution of this lineage. In certain cases, we can deduce that PCR-amplified sequences, some of which contain small introns, are localized in nuclear DNA. We infer that the T3/T7-like RNA polymerase sequences reported here are likely derived from genes encoding the mitochondrial RNA polymerase in the organisms in which they occur, suggesting a phage T3/T7-like RNA polymerase was recruited to act in transcription in the mitochondrion at an early stage in the evolution of this organelle.}, } @article {pmid8692049, year = {1996}, author = {Kozlov, AP}, title = {Gene competition and the possible evolutionary role of tumours.}, journal = {Medical hypotheses}, volume = {46}, number = {2}, pages = {81-84}, doi = {10.1016/s0306-9877(96)90005-5}, pmid = {8692049}, issn = {0306-9877}, mesh = {Animals ; *Biological Evolution ; Gene Expression Regulation, Neoplastic ; Humans ; Models, Genetic ; Multigene Family ; Neoplasms/*genetics/pathology ; Oncogenes ; }, abstract = {The evolutionary role of tumours might consist of providing the conditions for the expression of evolutionary new genes and thus in providing the material for the origin of new cell types. To approach this concept the principle of gene competition is essential. With an increase in gene number in the genomes of the evolving multicellular organisms the enforcement of gene competition should take place. Therefore, the pre-existing cell types possess limited possibilities for the expression of evolutionary new genes. Like evolutionary new genes originated from extra copies (duplicates) of old genes, evolutionary new cell types had to originate from extra cells which were not functionally necessary to the organism. Tumours could have supplied the evolving multicellular organisms with extra cells for the expression of originating evolutionary new genes. Of course, on the basis of this proposal only tumours at the earlier stages of progression are considered to be meaningful, or some kind of tumour-like processes, but not malignant tumours at late stages of progression. The evolutionary new genes originate in the DNA of germ line cells but not in DNA of tumour cells. Until the moment of their expression in the tumour cells these genes could stay silent. After the expression of these genes tumour cells should acquire the function in the organism, differentiate and lose their previous autonomy. The organisms with a new cell type should then be selected against their fitness and competitive abilities.}, } @article {pmid8570613, year = {1996}, author = {Hallmann, A and Sumper, M}, title = {The Chlorella hexose/H+ symporter is a useful selectable marker and biochemical reagent when expressed in Volvox.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {93}, number = {2}, pages = {669-673}, pmid = {8570613}, issn = {0027-8424}, mesh = {Amino Sugars ; Animals ; Base Sequence ; Biological Transport ; *Carbohydrate Metabolism ; Carrier Proteins/*genetics ; Chlorella/*genetics ; Cloning, Molecular ; Darkness ; Deoxyglucose/metabolism ; *Genetic Markers ; Glucosamine/metabolism ; Glucose/metabolism ; Membrane Proteins/*genetics ; Molecular Sequence Data ; *Monosaccharide Transport Proteins ; Polymerase Chain Reaction ; Selection, Genetic ; Sequence Analysis, DNA ; Symporters ; Transformation, Genetic ; Volvocida/*genetics ; }, abstract = {The multicellular obligately photoautotrophic alga Volvox is composed of only two types of cells, somatic and reproductive. Therefore, Volvox provides the simplest model system for the study of multicellularity. Metabolic labeling experiments using radioactive precursors are crucial for the detection of stage- and cell-type-specific proteins, glycoproteins, lipids, and carbohydrates. However, wild-type Volvox lacks import systems for sugars or amino acids. To circumvent this problem, the hexose/H+ symporter (HUP1) gene from the unicellular alga Chlorella was placed under the control of the constitutive Volvox beta-tubulin promoter. The corresponding transgenic Volvox strain synthesized the sugar transporter in a functional state and was able to efficiently incorporate 14C from labeled glucose or glucosamine. Sensitivity toward the toxic glucose/mannose analogue 2-deoxy-glucose increased by orders of magnitude in transformants. Thus we report the successful transformation of Volvox with a gene of heterologous origin. The chimeric gene may be selected for in either a positive or a negative manner, because transformants exhibit both prolonged survival in the dark in the presence of glucose and greatly increased sensitivity to the toxic sugar 2-deoxyglucose. The former trait may make the gene useful as a dominant selectable marker for use in transformation studies, whereas the latter trait may make it useful in development of a gene-targeting system.}, } @article {pmid8729576, year = {1996}, author = {Otsuka, J and Watanabe, H and Mori, KT}, title = {Evolution of transcriptional regulation system through promiscuous coupling of regulatory proteins with operons; suggestion from protein sequence similarities in Escherichia coli.}, journal = {Journal of theoretical biology}, volume = {178}, number = {2}, pages = {183-204}, doi = {10.1006/jtbi.1996.0016}, pmid = {8729576}, issn = {0022-5193}, mesh = {Amino Acid Sequence ; Bacterial Proteins/genetics ; Base Sequence ; *Biological Evolution ; Escherichia coli/genetics ; Gene Expression ; *Genes, Regulator ; *Models, Genetic ; Molecular Sequence Data ; *Operon ; Transcription Factors/*metabolism ; }, abstract = {As an advanced molecular study of the problems of the evolution of organisms, the transcriptional regulation system is studied by investigating the amino acid sequence similarities between the proteins in the regulation system of Escherichia coli in which the data of sequenced proteins as well as of regulator-regulon relationships are accumulated. The similarities between the proteins are calculated by the FASTA algorithm and their homology is also evaluated in terms of statistical significance with the use of the RDF2 program. This investigation reveals that the similarity between the regulatory protein and the regulated protein is hardly found, but many similarities are found between regulatory proteins and between regulated proteins. These similarity relations are compared with the regulator-regulon relationships ascertained experimentally. From this comparison, it is found that similar regulatory proteins rarely regulate the transcription of similar protein genes. As most of the highly similar proteins are considered to have diverged from a common ancestral protein, this finding strongly suggests the possibility that descendant regulatory proteins have been promiscuously coupled with descendant operons, independently of their ancestral regulator-regulon relationship, and that some of the couplings have been fixed by selection to form the present system of transcriptional regulation. The compatibility of such promiscuous coupling with regulatory organization is illustrated in the carbohydrate transport systems and the succeeding metabolic pathways, whose organization is comprehensive in sending nutritious substances to the central path of glycolysis under different environmental conditions. The benefit of flexibility in regulator-regulon relationships in evolutionary processes is also discussed in connection with the punctuational divergence of species in macroevolution and the cell differentiation in multicellular organisms.}, } @article {pmid9175266, year = {1996}, author = {Boute, N and Exposito, JY and Boury-Esnault, N and Vacelet, J and Noro, N and Miyazaki, K and Yoshizato, K and Garrone, R}, title = {Type IV collagen in sponges, the missing link in basement membrane ubiquity.}, journal = {Biology of the cell}, volume = {88}, number = {1-2}, pages = {37-44}, doi = {10.1016/s0248-4900(97)86829-3}, pmid = {9175266}, issn = {0248-4900}, mesh = {Amino Acid Sequence ; Animals ; Basement Membrane/chemistry ; Cloning, Molecular ; Collagen/*analysis ; DNA, Complementary/isolation & purification ; Genome ; Humans ; Molecular Sequence Data ; Oligonucleotide Probes ; Phylogeny ; Porifera/*chemistry ; Species Specificity ; }, abstract = {Basement membrane structures, or their main component, type IV collagen, have been detected in all multicellular animal species, except sponges. We cancel this exception by the demonstration of type IV collagenous sequences in a new marine sponge species by cDNA and genomic DNA studies. One of these sequences is long enough to demonstrate the specific characteristics of type IV collagen chains. The 12 cysteines are at conserved positions in the carboxyl-terminal non-helical NCl domain, as are the interruptions in the carboxyl-terminal end of the triple helical domain. The gene organization of the region coding for the NCl domain is similar to that of the human genes COL4A2, COL4A4 and COL4A6. An additional, shorter sequence suggests the presence of a second chain. The expected tissue localization of this collagen has been confirmed using polyclonal antibodies raised against a sponge recombinant protein. These results demonstrate that type IV collagen is representated in all animal phyla. It is actually the only known ubiquitous collagen and it has at least two different alpha chains in all the species where it has been characterized.}, } @article {pmid8734297, year = {1996}, author = {Baeuerle, PA and Rupec, RA and Pahl, HL}, title = {Reactive oxygen intermediates as second messengers of a general pathogen response.}, journal = {Pathologie-biologie}, volume = {44}, number = {1}, pages = {29-35}, pmid = {8734297}, issn = {0369-8114}, mesh = {Humans ; Hydrogen Peroxide/*metabolism ; NF-kappa B/*metabolism ; Superoxides/*metabolism ; }, abstract = {Oxygen and derived ROIs became a threat for all organisms more than two billion years ago. Both prokaryotic and higher eukaryotic cells are able to alter their genetic programme in response to changes in the intracellular levels of reactive oxygen intermediates (ROIs). In bacteria and yeast, this response leads to the new synthesis of proteins that protect the induced cells from the consequences of oxidative damage, such as DNA strand breaks, lipid peroxidation and oxidative damage of proteins, thereby ensuring growth in a prooxidant environment. In higher eukaryotic cells, oxidative stress can be the consequence of reoxygenation of ischemic tissus or of exposure to environmental hazards. Intriguingly, multicellular organisms have also evolved cellular mechanisms to actively produce ROIs. In one case, the reactive compounds are needed as weapons against invading microorganisms. Granulocytes, neutrophils and macrophages have specialized in releasing of large amounts of H2O2 and superoxide. However, many other cell types can also inducibly produce ROIs but in amounts insufficient to threat microorganisms. There is increasing evidence that the small increases in ROI levels fulfil a role as second messengers. We propose that these pandemic pathogens have been conserved throughout evolution as universal pathogen messengers turning on genes with important functions in the immune response and cell proliferation. The higher eukaryotic transcription factor NF-kappa B will be described as a protein which is activated by ROIs under a great variety of pathogenic conditions and initiates the new expression of genes with important roles in inflammatory, immune and acute phase responses.}, } @article {pmid8853518, year = {1995}, author = {Parfitt, AM}, title = {Bone remodeling, normal and abnormal: a biological basis for the understanding of cancer-related bone disease and its treatment.}, journal = {The Canadian journal of oncology}, volume = {5 Suppl 1}, number = {}, pages = {1-10}, pmid = {8853518}, issn = {1183-2509}, mesh = {Biology ; Bone Diseases/drug therapy/*etiology ; Bone Marrow/pathology ; *Bone Remodeling/physiology ; Bone Resorption/physiopathology ; Bone and Bones/metabolism/physiology ; Cytokines/physiology ; Diphosphonates/therapeutic use ; Hematopoietic Stem Cells/physiology ; Humans ; Neoplasm Proteins/physiology ; Neoplasms/*complications/pathology/physiopathology ; Neoplastic Cells, Circulating/pathology ; Osteoblasts/physiology ; Osteoclasts/physiology ; Osteogenesis/physiology ; Parathyroid Hormone/physiology ; Parathyroid Hormone-Related Protein ; Proteins/physiology ; }, abstract = {Remodeling the cyclical replacement of old bone by new, serves to maintain its mechanical and metabolic functions. In each cycle a circumscribed volume of bone is removed by osteoclastic resorption and subsequently replaced by osteoblastic formation at the same location. Remodeling is carried out by elongated structures known as basic multicellular units (BMU) that travel through or across the surface of bone. Each BMU lasts about six months, with continued sequential recruitment of new osteoclasts and osteoblasts. Abnormal bone remodeling involves some combination of loss of directional control, increase in number of remodeling cycles and incomplete replacement. In metastatic bone disease, tumor cells find the hematopoietic bone marrow conducive to their survival and growth, because they can manipulate the local cytokine network to increase recruitment of osteoclasts from local precursors and so increase bone resorption. The effect on bone formation is biphasic; an initial increase is due partly to the normal evolution of the BMU, and partly to the induction of reparative woven bone formation. Later, normal BMU-based bone formation may fall to subnormal levels. In some tumors, a generalized increase in osteoclast recruitment and decline in bone formation are the systemic responses to one or more agents released by tumor cells into the circulation, of which the most frequent is parathyroid hormone-related peptide, but in both metastatic and non-metastatic disease, the cellular events in bone are essentially the same. Cancer-related bone disease is amenable to treatment with drugs that inhibit osteoclast recruitment, of which the bisphosphonates are the most effective. Treatment should be started before there has been irreparable damage to bone structure and before the onset of hypercalcemia. Although bisphosphonates remain in bone for a long time, adverse effects are very unlikely within the patient's lifetime.}, } @article {pmid8771049, year = {1995}, author = {Grossgebauer, K}, title = {The 'cancell' theory of carcinogenesis: re-evolution of an ancient, holistic neoplastic unicellular concept of cancer.}, journal = {Medical hypotheses}, volume = {45}, number = {6}, pages = {545-555}, doi = {10.1016/0306-9877(95)90238-4}, pmid = {8771049}, issn = {0306-9877}, mesh = {Animals ; Biological Evolution ; Carcinogens/toxicity ; Cell Transformation, Neoplastic/genetics ; DNA/genetics ; Humans ; *Models, Biological ; Neoplasms/*etiology/genetics ; }, abstract = {The 'cancell' theory of carcinogenesis is based on four assumptions: 1. that there is early evolvement of neoplastic potentials in certain unicellular eukaryotes (so-called cancell lines) by adaptive response to the various carcinogens of the primitive Earth. The process that led to the neoplastic potential is called 'early carcinogenesis'; 2. that there is transition of cancell lines to multicellular forms; 3. that there is uptake of the basic genetics and epigenetics of the cancell concept into the genomic program of multicellular entities and their conservation even in human cells, and 4. the re-emergence of the ancient cancell concept in human somatic cells in a process called 'late carcinogenesis'. According to this theory, both processes of carcinogenesis, the early one and the late one, are thought to be the result of a physiological adaptive response to the various genotoxic and nongenotoxic carcinogens.}, } @article {pmid8582622, year = {1995}, author = {Otto, SP and Orive, ME}, title = {Evolutionary consequences of mutation and selection within an individual.}, journal = {Genetics}, volume = {141}, number = {3}, pages = {1173-1187}, pmid = {8582622}, issn = {0016-6731}, support = {GM-40282/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Cell Death ; Cell Division ; *Cell Lineage ; Extrachromosomal Inheritance ; Haploidy ; Models, Genetic ; Mutation ; Organelles ; Selection, Genetic ; }, abstract = {Whether in sexual or asexual organisms, selection among cell lineages during development is an effective way of eliminating deleterious mutations. Using a mathematical analysis, we find that relatively small differences in cell replication rates during development can translate into large differences in the proportion of mutant cells within the adult, especially when development involves a large number of cell divisions. Consequently, intraorganismal selection can substantially reduce the deleterious mutation rate observed among offspring as well as the mutation load within a population, because cells rather than individuals provide the selective "deaths" necessary to stem the tide of deleterious mutations. The reduction in mutation rate among offspring is more pronounced in organisms with plastic development than in those with structured development. It is also more pronounced in asexual organisms that produce multicellular rather than unicellular offspring. By effecting the mutation rate, intraorganismal selection may have broad evolutionary implications; as an example, we consider its influence on the evolution of ploidy levels, finding that cell-lineage selection is more effective in haploids and tends to favor their evolution.}, } @article {pmid8520588, year = {1995}, author = {Custodio, MR and Imsiecke, G and Borojevic, R and Rinkevich, B and Rogerson, A and Müller, WE}, title = {Evolution of cell adhesion systems: evidence for Arg-Gly-Asp-mediated adhesion in the protozoan Neoparamoeba aestuarina.}, journal = {The Journal of eukaryotic microbiology}, volume = {42}, number = {6}, pages = {721-724}, doi = {10.1111/j.1550-7408.1995.tb01623.x}, pmid = {8520588}, issn = {1066-5234}, mesh = {Amino Acid Sequence ; Animals ; Cell Adhesion/drug effects/*physiology ; Eukaryota/cytology/drug effects/*physiology ; Molecular Sequence Data ; Oligopeptides/*pharmacology ; Structure-Activity Relationship ; }, abstract = {Developmental processes in multicellular organisms require structural elements, such as adhesion molecules, to stabilize cells at functional positions. In vertebrates, a series of extracellular matrix proteins, e.g. fibronectin and laminin, are involved in cell adhesion. These proteins contain Arg-Gly-Asp [RGD] at their binding sites. Here we show that at concentrations above 2 mM the peptide GRGDSPK, comprising the tripeptide RGD (Arg-Gly-Asp), prevents the adhesiveness of cells of the marine amoeba Neoparamoeba aestuarina. In addition, elevated levels of GRGDSPK cause cells to alter their shapes from those with digitiform subpseudopodia to rounded cells with small lobed pseudopodia. These cells detach from the substratum. These results are specific for the RGD sequence, because incubation in GRGESPK solution at the same concentrations had no effect on cell attachment or structure. From these data we suggest that the structural adhesion molecules identified in vertebrates show amino acid homologies with those found in unicellular protozoa.}, } @article {pmid8596463, year = {1995}, author = {Bruton, CJ and Plaskitt, KA and Chater, KF}, title = {Tissue-specific glycogen branching isoenzymes in a multicellular prokaryote, Streptomyces coelicolor A3(2).}, journal = {Molecular microbiology}, volume = {18}, number = {1}, pages = {89-99}, doi = {10.1111/j.1365-2958.1995.mmi_18010089.x}, pmid = {8596463}, issn = {0950-382X}, mesh = {1,4-alpha-Glucan Branching Enzyme/*genetics ; Amino Acid Sequence ; Base Sequence ; Biological Evolution ; Cell Differentiation ; Chromosome Mapping ; Gene Library ; *Genes, Bacterial ; Glycogen/*biosynthesis/ultrastructure ; Isoenzymes/*genetics ; Molecular Sequence Data ; Mutagenesis ; Sequence Analysis, DNA ; Streptomyces/enzymology/*genetics/growth & development/ultrastructure ; Tissue Distribution ; }, abstract = {In the overtly differentiated colonies of Streptomyces coelicolor A3(2), discrete phases of glycogen synthesis are found at the vegetative/aerial mycelium boundary (phase I) and in the immature spore chains at aerial hyphal tips (phase II). We have characterized two S. coelicolor glgB genes encoding glycogen branching enzyme, which are well separated in the genome. Disruption of glgBl led to the formation of abnormal polyglucan deposits at phase I, with phase II remaining normal, whereas disruption of glgBII interfered specifically with phase II deposits, and not with those of phase I. Thus, each branching enzyme isoform is involved in a different phase of glycogen synthesis. This situation contrasts with that in simple bacteria, which typically have a single set of enzymes for glycogen metabolism, and more closely resembles that in plants.}, } @article {pmid8577298, year = {1995}, author = {Holt, JA}, title = {Some characteristics of the glutathione cycle revealed by ionising and non-ionising electromagnetic radiation.}, journal = {Medical hypotheses}, volume = {45}, number = {4}, pages = {345-368}, doi = {10.1016/0306-9877(95)90095-0}, pmid = {8577298}, issn = {0306-9877}, mesh = {Adolescent ; Adult ; Aerobiosis ; Anaerobiosis ; Animals ; *Biological Evolution ; Brain/physiology ; Cell Nucleus/metabolism ; Civilization ; Clinical Trials as Topic ; Combined Modality Therapy ; *Energy Metabolism ; Feedback ; Female ; Glutathione/*metabolism/radiation effects ; Glycolysis ; Humans ; Hyperthermia, Induced ; Intelligence ; Male ; Microwaves/therapeutic use ; Middle Aged ; Mitosis ; *Models, Biological ; Neoplasms/metabolism/radiotherapy/*therapy ; Neuroglia/physiology ; Neurons/physiology ; *Origin of Life ; Oxidation-Reduction ; Population Dynamics ; *Radiation ; Radiation Tolerance ; Radiotherapy Dosage ; }, abstract = {The cyclic reaction of GSH-->GSSG-->GSH (designated R(exp) or R(e)) obeys the three specific features of life by producing energy in exponential quantities relative to time, is in effect irreversible and is inherited from generation to generation. In multicellular life, this reaction produces the energy for mitosis and is kept in controlled inactivity until needed to maintain perfection of form and function by energising mitosis. The immediate control of Re appears to be feedback process-dependent on the concentration of GSSG. Ultra high-frequency electromagnetic radiation of 434 MHz (UHF) will change Re from inactive to active and, in so doing, it causes resonance and/or fluorescence of the glutathione cycle which changes its radiosensitivity. Re is the primary direct target of ionising radiation and produces the energy for mitosis. Clinical observations suggest that, in the normal cell, Re is inactive and is not killed by 3 x 2700 rads or 6 x 1650 rads yet, when active, its sensitivity value (DO) is approximately 160 rads. Using the standard radiobiological equation of response to ionising radiation, it can be deduced that radiosensitive cancers have two or three Re units active per cell and radioresistance increases in proportion to the number of potentially active Re units per cell. Re appears to be the main cause of cancers' increased conductivity of electricity compared with normal tissue. In cancer therapy, UHF is the best radiosensitiser ever discovered (up to two or more decades). Re is also intelligent compared with non-exponential reactions but cannot be the basis of intellectual brain functions which must be based on non-electrical chemical processes.}, } @article {pmid8541419, year = {1995}, author = {Katayama, T and Wada, H and Furuya, H and Satoh, N and Yamamoto, M}, title = {Phylogenetic position of the dicyemid mesozoa inferred from 18S rDNA sequences.}, journal = {The Biological bulletin}, volume = {189}, number = {2}, pages = {81-90}, doi = {10.2307/1542458}, pmid = {8541419}, issn = {0006-3185}, mesh = {Animals ; Base Sequence ; DNA Primers ; DNA, Ribosomal/*genetics ; Invertebrates/*classification/genetics ; Molecular Sequence Data ; Mollusca/parasitology ; Phylogeny ; RNA, Ribosomal, 18S/*genetics ; Sequence Homology, Nucleic Acid ; Symbiosis ; }, abstract = {The dicyemid mesozoa, obligate symbionts in the cephalopod kidney, are simply organized multicellular animals. They have long been the subject of phylogenetic debates. Some authors have suggested that dicyemids represent an offshoot from an early metazoan ancestor. Other workers considered them to be degenerated progeny of higher metazoa, possibly parasitic trematodes. We determined the almost complete nucleotide sequences of 18S rDNA in two species of dicyemid, Dicyema orientale and Dicyema acuticephalum, isolated purely from cephalopod urine. We compared these sequences with sequences determined in the present study from three flatworm species, as well as with a variety of eukaryote sequences obtained from databases. The phylogenetic trees reconstructed with the use of the neighbor-joining, maximum-parsimony, and maximum-likelihood methods indicated that the dicyemids belong among the triploblastic animals (Bilateria). However, we cannot firmly establish the position of the dicyemids within the Bilateria because we cannot ignore the problem of long branch attraction between the myxozoans, dicyemids, nematodes, and acoel flatworms. The present results favor the hypothesis that the dicyemids do not represent an early divergent metazoan group, but rather a group degenerated from a triploblastic ancestor.}, } @article {pmid7565716, year = {1995}, author = {Zhou, K and Takegawa, K and Emr, SD and Firtel, RA}, title = {A phosphatidylinositol (PI) kinase gene family in Dictyostelium discoideum: biological roles of putative mammalian p110 and yeast Vps34p PI 3-kinase homologs during growth and development.}, journal = {Molecular and cellular biology}, volume = {15}, number = {10}, pages = {5645-5656}, pmid = {7565716}, issn = {0270-7306}, support = {CA60559/CA/NCI NIH HHS/United States ; }, mesh = {1-Phosphatidylinositol 4-Kinase ; Amino Acid Sequence ; Animals ; Base Sequence ; Cloning, Molecular ; Conserved Sequence ; Dictyostelium/*enzymology/genetics/growth & development ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Fungal ; Genes, Fungal/*genetics ; Mammals/genetics ; Molecular Sequence Data ; Multigene Family/*genetics ; Phosphatidylinositol 3-Kinases ; Phosphotransferases (Alcohol Group Acceptor)/genetics/*physiology ; Phylogeny ; RNA, Antisense/genetics ; *Saccharomyces cerevisiae Proteins ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; }, abstract = {Three groups of phosphatidylinositol (PI) kinases convert PI into PI(3)phosphate, PI(4)phosphate, PI(4,5) bisphosphate, and PI(3,4,5)trisphosphate. These phosphoinositides have been shown to function in vesicle-mediated protein sorting, and they serve as second-messenger signaling molecules for regulating cell growth. To further elucidate the mechanism of regulation and function of phosphoinositides, we cloned genes encoding five putative PI kinases from Dictyostelium discoideum. Database analysis indicates that D. discoideum PIK1 (DdPIK1), -2, and -3 are most closely related to the mammalian p110 PI 3-kinase, DdPIK5 is closest to the yeast Vps34p PI 3-kinase, and DdPIK4 is most homologous to PI 4-kinases. Together with other known PI kinases, a superfamily of PI kinase genes has been defined, with all of the encoded proteins sharing a common highly conserved catalytic core domain. DdPIK1, -2, and -3 may have redundant functions because disruption of any single gene had no effect on D. discoideum growth or development. However, strains in which both of the two most highly related genes, DdPIK1 and DdPIK2, were disrupted showed both growth and developmental defects, while double knockouts of DdPIK1 and DdPIK3 and DdPIK2 and DdPIK3 appear to be lethal. The delta Ddpik1 delta Ddpik2 null cells were smaller than wild-type cells and grew slowly both in association with bacteria and in axenic medium when attached to petri plates but were unable to grow in suspension in axenic medium. When delta Ddpik1 delta Ddpik2 null cells were plated for multicellular development, they formed aggregates having multiple tips and produced abnormal fruiting bodies. Antisense expression of DdPIK5 (a putative homolog of the Saccharomyces cerevisiae VPS34) led to a defect in the growth of D. discoideum cells on bacterial lawns and abnormal development. DdPIK5 complemented the temperature-sensitive growth defect of a Schizosaccharomyces pombe delta Svps34 mutant strain, suggesting DdPIK5 encodes a functional homolog of yeast Vps34p. These observations indicate that in D. discoideum, different PI kinases regulate distinct cellular processes, including cell growth, development, and protein trafficking.}, } @article {pmid7563127, year = {1995}, author = {Riley, DE and Krieger, JN}, title = {Molecular and phylogenetic analysis of PCR-amplified cyclin-dependent kinase (CDK) family sequences from representatives of the earliest available lineages of eukaryotes.}, journal = {Journal of molecular evolution}, volume = {41}, number = {4}, pages = {407-413}, pmid = {7563127}, issn = {0022-2844}, support = {R01 DK38955/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Confidence Intervals ; Cyclin-Dependent Kinases/chemistry/*genetics ; DNA Primers ; DNA, Protozoan/chemistry/genetics/isolation & purification ; Eukaryota/genetics ; Eukaryotic Cells/enzymology ; Fungi/genetics ; Genetic Variation ; Giardia lamblia/enzymology/genetics ; Humans ; Molecular Sequence Data ; *Phylogeny ; Polymerase Chain Reaction/methods ; Sequence Homology, Amino Acid ; Trichomonas vaginalis/enzymology/genetics/isolation & purification ; Vertebrates/genetics ; }, abstract = {Cyclin-dependent kinase (CDK) and cell division control (CDC2) sequences are strongly conserved among eukaryotes and may complement the use of other sequence families in eukaryotic phylogenetic inference. We synthesized degenerate PCR primers to amplify the catalytic region of CDK homologs in representatives of the earliest available lineages of eukaryotes. CDK family sequence-based, maximum-likelihood distance measurements with neighbor-joining, and Fitch-Margoliash least-squares analyses produced unrooted dendrograms that included protists, yeasts, and higher eukaryotes. Bootstrap confidence estimates supported CDK-based phylogenetic groupings among the protists, fungi, and vertebrates although resolution within these groups was often insignificant. However, Trichomonas vaginalis and Giardia lamblia exhibited two of the most divergent CDK-like sequences consistent with rRNA-phylogenetic inference of early divergence of these eukaryotic lineages. In the evolution from unicellular to multicellular organisms, a constellation of amino acid residues aligning with the human, CDK N-terminal beta sheet may have undergone abrupt replacement.}, } @article {pmid8577834, year = {1995}, author = {Sharp, PM and Averof, M and Lloyd, AT and Matassi, G and Peden, JF}, title = {DNA sequence evolution: the sounds of silence.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {349}, number = {1329}, pages = {241-247}, doi = {10.1098/rstb.1995.0108}, pmid = {8577834}, issn = {0962-8436}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Base Sequence ; *Codon ; *DNA ; Drosophila/genetics ; *Evolution, Molecular ; Genetic Variation ; Genome ; Humans ; Mammals/genetics ; Models, Genetic ; Molecular Sequence Data ; Mutation ; Saccharomyces cerevisiae/genetics ; Selection, Genetic ; }, abstract = {Silent sites (positions that can undergo synonymous substitutions) in protein-coding genes can illuminate two evolutionary processes. First, despite being silent, they may be subject to natural selection. Among eukaryotes this is exemplified by yeast, where synonymous codon usage patterns are shaped by selection for particular codons that are more efficiently and/or accurately translated by the most abundant tRNAs; codon usage across the genome, and the abundance of different tRNA species, are highly co-adapted. Second, in the absence of selection, silent sites reveal underlying mutational patterns. Codon usage varies enormously among human genes, and yet silent sites do not appear to be influenced by natural selection, suggesting that mutation patterns vary among regions of the genome. At first, the yeast and human genomes were thought to reflect a dichotomy between unicellular and multicellular organisms. However, it now appears that natural selection shapes codon usage in some multicellular species (e.g. Drosophila and Caenorhabditis), and that regional variations in mutation biases occur in yeast. Silent sites (in serine codons) also provide evidence for mutational events changing adjacent nucleotides simultaneously.}, } @article {pmid7475100, year = {1995}, author = {Markos, A}, title = {The ontogeny of Gaia: the role of microorganisms in planetary information network.}, journal = {Journal of theoretical biology}, volume = {176}, number = {1}, pages = {175-180}, doi = {10.1006/jtbi.1995.0186}, pmid = {7475100}, issn = {0022-5193}, mesh = {Animals ; *Bacteria ; *Biological Evolution ; *Ecosystem ; *Genes ; Models, Biological ; Signal Transduction ; }, abstract = {The Gaia theory states that the whole surface layer of the globe, including organisms, atmosphere, hydrosphere and lithosphere, can be viewed as a self-evolving homeostatic system. Bacteria play a principal role in this formative process. This line of thinking should answer several questions: Is the biosphere simply a set of essentially selfish individuals, each testing its fitness? Is memory in the biosphere confined to genes? Is the composition of ecosystems and their behavior only kind of dynamic equilibrium? Or is there a huge amount of epigenetic information that enables organisms to interpret properly their situation and behave accordingly? It is suggested here that it is the information flow, rather than pure thermodynamics and natural selection, that enables living beings not only to "read" their environment, interpret their situation and behave accordingly to this understanding, but also to establish geophysiology, to become part of Gaia. This flow comprises genes as well as signals, diffusible as well as permanent. From an analogy with the situation in the multicellular organism, three types of information mediators inside the body of Gaia are suggested: ultrastructure, diffusible signals and gene flux. With a shared gene pool, intricate ultrastructure and quickly diffusible signals, it is legitimate to consider Gaia a superorganism with an ontogeny.}, } @article {pmid7556181, year = {1995}, author = {Kuusksalu, A and Pihlak, A and Müller, WE and Kelve, M}, title = {The (2'-5')oligoadenylate synthetase is present in the lowest multicellular organisms, the marine sponges. Demonstration of the existence and identification of its reaction products.}, journal = {European journal of biochemistry}, volume = {232}, number = {2}, pages = {351-357}, pmid = {7556181}, issn = {0014-2956}, mesh = {2',5'-Oligoadenylate Synthetase/chemistry/immunology/*metabolism ; Adenine Nucleotides/isolation & purification/metabolism/pharmacology ; Animals ; Biological Evolution ; Blood Proteins/biosynthesis ; Blotting, Western ; Chromatography, High Pressure Liquid ; Cross Reactions ; Immunochemistry ; In Vitro Techniques ; Mice ; Molecular Weight ; Oligoribonucleotides/isolation & purification/metabolism/pharmacology ; Porifera/*enzymology/metabolism ; Protein Synthesis Inhibitors/isolation & purification/metabolism/pharmacology ; Rabbits ; Rats ; Reticulocytes/drug effects/metabolism ; Species Specificity ; }, abstract = {We have proved the presence of (2'-5')oligoadenylates [(2'-5')An] and oligoadenylate synthetase [(2'-5')An synthetase] in the marine sponge Geodia cydonium. (2'-5')An isolated from sponge crude extract competed with authentic (2'-5')An for binding to polyclonal antiserum against (2'-5')An. HPLC analysis revealed the presence of nucleotides eluting with molecular markers for (2'-5')A oligomers. The biological activity of sponge (2'-5')An was demonstrated by inhibiting the protein biosynthesis in rabbit reticulocyte lysate. The activity of the (2'-5')An synthetase, present in crude sponge extract, was found to be high compared to that in mammalian interferon-treated cell extract. The (2'-5')An synthetase from sponge extract binds to poly(I).poly(C) as does the mammalian enzyme. Western blot analysis with antibodies to recombinant rat 43-kDa (2'-5')An synthetase revealed in sponge immunologically related proteins with molecular masses of approximately 110, 65, 61 and 34 kDa. We conclude, that the (2'-5')An system has evolved from receptors and enzymes involved in cell adhesion and/or growth control.}, } @article {pmid7666445, year = {1995}, author = {Newfeld, SJ and Gelbart, WM}, title = {Identification of two Drosophila TGF-beta family members in the grasshopper Schistocerca americana.}, journal = {Journal of molecular evolution}, volume = {41}, number = {2}, pages = {155-160}, pmid = {7666445}, issn = {0022-2844}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Biological Evolution ; Bone Morphogenetic Proteins ; *Drosophila Proteins ; Drosophila melanogaster/*genetics ; Gene Dosage ; Genes, Insect/*genetics ; Grasshoppers/*genetics ; Hominidae/genetics ; Humans ; Insect Hormones/*genetics ; Molecular Sequence Data ; Proteins/genetics ; RNA, Messenger/analysis ; Sequence Alignment ; Sequence Homology, Amino Acid ; Transforming Growth Factor beta/*genetics ; }, abstract = {Intercellular signaling molecules of the transforming growth factor-beta (TGF-beta) superfamily are required for pattern formation in many multicellular organisms. The decapentaplegic (dpp) gene of Drosophila melanogaster has several developmental roles. To improve our understanding of the evolutionary diversification of this large family we identified dpp in the grasshopper Schistocerca americana. S. americana diverged from D. melanogaster approximately 350 million years ago, utilizes a distinct developmental program, and has a 60-fold-larger genome than D. melanogaster. Our analyses indicate a single dpp locus in D. melanogaster and S. americana, suggesting that dpp copy number does not correlate with increasing genome size. Another TGF-beta superfamily member, the D. melanogaster gene 60A, is also present in only one copy in each species. Comparison of homologous sequences from D. melanogaster, S. americana, and H. sapiens, representing roughly 900 million years of evolutionary distance, reveals significant constraint on sequence divergence for both dpp and 60A. In the signaling portion of the dpp protein, the amino acid identity between these species exceeds 74%. Our results for the TGF-beta superfamily are consistent with current hypotheses describing gene duplication and diversification as a frequent response to high levels of selective pressure on individual family members.}, } @article {pmid11536694, year = {1995}, author = {Logan, GA and Hayes, JM and Hieshima, GB and Summons, RE}, title = {Terminal Proterozoic reorganization of biogeochemical cycles.}, journal = {Nature}, volume = {376}, number = {6535}, pages = {53-56}, doi = {10.1038/376053a0}, pmid = {11536694}, issn = {0028-0836}, mesh = {Carbon/chemistry ; Carbon Isotopes ; Fossils ; Geologic Sediments/*chemistry ; Hydrocarbons/*analysis ; Models, Biological ; Models, Chemical ; Oxidation-Reduction ; Oxygen/*chemistry/metabolism ; *Paleontology ; Seawater ; Sulfur Isotopes ; Sulfur-Reducing Bacteria ; }, abstract = {The Proterozoic aeon (2,500-540 million years ago) saw episodic increases in atmospheric oxygen content, the evolution of multicellular life and, at its close, an enormous radiation of animal diversity. These profound biological and environmental changes must have been linked, but the underlying mechanisms have been obscure. Here we show that hydrocarbons extracted from Proterozoic sediments in several locations worldwide are derived mainly from bacteria or other heterotrophs rather than from photosynthetic organisms. Biodegradation of algal products in sedimenting matter was therefore unusually complete, indicating that organic material was extensively reworked as it sank slowly through the water column. We propose that a significant proportion of this reworking will have been mediated by sulphate-reducing bacteria, forming sulphide. The production of sulphide and consumption of oxygen near the ocean surface will have inhibited transport of O2 to the deep ocean. We find that preservation of algal-lipid skeletons improves at the beginning of the Cambrian, reflecting the increase in transport by rapidly sinking faecal pellets. We suggest that this rapid removal of organic matter will have increased oxygenation of surface waters, leading to a descent of the O2-sulphide interface to the sea floor and to marked changes in the marine environment, ultimately contributing to the Cambrian radiation.}, } @article {pmid8590468, year = {1995}, author = {Bouget, FY and Kerbourc'h, C and Liaud, MF and Loiseaux de Goër, S and Quatrano, RS and Cerff, R and Kloareg, B}, title = {Structural features and phylogeny of the actin gene of Chondrus crispus (Gigartinales, Rhodophyta).}, journal = {Current genetics}, volume = {28}, number = {2}, pages = {164-172}, pmid = {8590468}, issn = {0172-8083}, mesh = {Actins/*genetics ; Amino Acid Sequence ; Base Sequence ; Blotting, Southern ; DNA, Complementary ; Molecular Sequence Data ; *Phylogeny ; Rhodophyta/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {We have characterized the cDNA and genomic sequences that encode actin from the multicellular red alga Chondrus crispus. Southern-blot analysis indicates that the C. crispus actin gene (ChAc) is present as a single copy. Northern analysis shows that, like the GapA gene, the actin gene is well expressed in gametophytes but weakly in protoplasts. Compared to actin genes of animals, fungi, green plants and oomycetes, that of C. crispus displays a higher evolutionary rate and does not show any of the amino-acid signatures characteristic of the other lineages. As previously described for GapA, ChAc is interrupted by a single intron at the beginning of the coding region. The site of initiation of transcription was characterized by RNAse protection. The promoter region displays a CAAT box but lacks a canonical TATA motif. Other noticeable features, such as a high content of pyrimidines as well as a 14-nt motif found in both the 5'-untranslated region and the intron, were observed.}, } @article {pmid7646482, year = {1995}, author = {Shapiro, JA}, title = {The significances of bacterial colony patterns.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {17}, number = {7}, pages = {597-607}, doi = {10.1002/bies.950170706}, pmid = {7646482}, issn = {0265-9247}, mesh = {Bacteria/genetics/*growth & development ; DNA, Bacterial ; }, abstract = {Bacteria do many things as organized populations. We have recently learned much about the molecular basis of intercellular communication among prokaryotes. Colonies display bacterial capacities for multicellular coordination which can be useful in nature where bacteria predominantly grow as films, chains, mats and colonies. E. coli colonies are organized into differentiated non-clonal populations and undergo complex morphogenesis. Multicellularity regulates many aspects of bacterial physiology, including DNA rearrangement systems. In some bacterial species, colony development involves swarming (active migration of cell groups). Swarm colony development displays precise geometrical controls and periodic phenomena. Motile E. coli cells in semi-solid media form organized patterns due to chemotactic autoaggregation. On poor media, B. subtilis forms branched colonies using group motility and long-range chemical signalling. The significances of bacterial colony patterns thus reside in a deeper understanding of prokaryotic biology and evolution and in experimental systems for studying self-organization and morphogenesis.}, } @article {pmid7643908, year = {1995}, author = {Müller, WE}, title = {Molecular phylogeny of Metazoa (animals): monophyletic origin.}, journal = {Die Naturwissenschaften}, volume = {82}, number = {7}, pages = {321-329}, pmid = {7643908}, issn = {0028-1042}, mesh = {Amino Acid Sequence ; Animals ; Invertebrates/*classification/*genetics ; Lectins/genetics ; Molecular Sequence Data ; *Phylogeny ; Porifera/classification/genetics ; Receptor Protein-Tyrosine Kinases/chemistry/genetics ; }, abstract = {The phylogenetic relationships within the kingdom Animalia (Metazoa) have long been questioned. Focusing on the lowest eukaryotic multicellular organisms, the metazoan phylum Porifera (sponges), it remained unsolved if they evolved multicellularity independently from a separate protist lineage (polyphyly of animals) of derived from the same protist group as the other animal phyla (monophyly). After having analyzed genes typical for multicellularity (adhesion molecules/receptors and a nuclear receptor), we present evidence that Porifera should be placed in the kingdom Animalia. We therefore suggest a monophyletic origin for all animals.}, } @article {pmid7597031, year = {1995}, author = {Escalante, AA and Ayala, FJ}, title = {Evolutionary origin of Plasmodium and other Apicomplexa based on rRNA genes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {92}, number = {13}, pages = {5793-5797}, pmid = {7597031}, issn = {0027-8424}, support = {GM42397/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Apicomplexa/classification/*genetics/pathogenicity ; *Biological Evolution ; Disease Vectors ; Fungi/genetics ; *Genes, Protozoan ; Humans ; Insect Vectors ; Molecular Sequence Data ; Phylogeny ; Plants/genetics ; Plasmodium/classification/*genetics/pathogenicity ; RNA, Ribosomal/*genetics ; }, abstract = {We have explored the evolutionary history of the Apicomplexa and two related protistan phyla, Dinozoa and Ciliophora, by comparing the nucleotide sequences of small subunit ribosomal RNA genes. We conclude that the Plasmodium lineage, to which the malarial parasites belong, diverged from other apicomplexan lineages (piroplasmids and coccidians) several hundred million years ago, perhaps even before the Cambrian. The Plasmodium radiation, which gave rise to several species parasitic to humans, occurred approximately 129 million years ago; Plasmodium parasitism of humans has independently arisen several times. The origin of apicomplexans (Plasmodium), dinoflagellates, and ciliates may be > 1 billion years old, perhaps older than the three multicellular kingdoms of animals, plants, and fungi. Digenetic parasitism independently evolved several times in the Apicomplexa.}, } @article {pmid7580262, year = {1995}, author = {Grimm, D and Bauer, J and Kromer, E and Steinbach, P and Riegger, G and Hofstädter, F}, title = {Human follicular and papillary thyroid carcinoma cells interact differently with human venous endothelial cells.}, journal = {Thyroid : official journal of the American Thyroid Association}, volume = {5}, number = {3}, pages = {155-164}, doi = {10.1089/thy.1995.5.155}, pmid = {7580262}, issn = {1050-7256}, mesh = {Adenocarcinoma, Follicular/*pathology ; Adenoma/pathology ; Carcinoma, Papillary/*pathology ; Cell Adhesion ; Cell Movement ; Coculture Techniques ; Endothelium, Vascular/*cytology ; Humans ; Microscopy, Phase-Contrast ; Spheroids, Cellular/*physiology ; Thyroid Neoplasms/*pathology ; Veins/*cytology ; }, abstract = {Follicular thyroid carcinomas (FTC) characteristically spread via blood vessels, while papillary thyroid carcinomas (PTC) predominantly metastasize to lymph nodes. This different behavior of cancer cells originating from one organ was investigated by layering multicellular tumor spheroids (MCTS) consisting of various kinds of human thyroid cells onto confluent monolayers of human venous endothelial cells (HEC). The MCTS and HEC were cocultured in an incubation chamber fixed under a microscope, and the behavior of the cells was investigated. In this way significant differences between FTC, PTC, and follicular adenoma cells (FTA) were observed regarding their in vitro behavior upon interaction with HEC. FTC cells required 20 min for adhesion and another hour until they migrated out of a spheroid, whereas PTC- and FTA-MCTS were adhesive after 2 h or later, and their cells did not start migration until 5 h of incubation. Furthermore, one FTC-spheroid triggered about 100 endothelial cells to enter the replication cycle, while no spheroid consisting of either PTC or FTA cells induced more than 20 endothelial cells to start proliferation. During these processes, the cells of the MCTS and the endothelial cells contacted each other directly and remained viable. The results show that FTC cells interact faster and more intensively with human endothelial cells than PTC and FTA cells. Thus the study suggests that an enhanced capability of the FTC cells to interact with venous endothelial cells might favor the clinically observed hematogenous spreading of follicular thyroid carcinomas.}, } @article {pmid7739382, year = {1995}, author = {Claudianos, C and Campbell, HD}, title = {The novel flightless-I gene brings together two gene families, actin-binding proteins related to gelsolin and leucine-rich-repeat proteins involved in Ras signal transduction.}, journal = {Molecular biology and evolution}, volume = {12}, number = {3}, pages = {405-414}, doi = {10.1093/oxfordjournals.molbev.a040215}, pmid = {7739382}, issn = {0737-4038}, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans/genetics ; *Drosophila Proteins ; Drosophila melanogaster/genetics ; Gelsolin/*genetics ; Genes, ras/*genetics ; Humans ; Leucine/*chemistry ; Mice ; Microfilament Proteins/*genetics ; Molecular Sequence Data ; Phylogeny ; Proteins/*genetics ; Repetitive Sequences, Nucleic Acid ; Sequence Alignment ; Signal Transduction/*genetics ; }, abstract = {The Drosophila melanogaster gene flightless-I, involved in gastrulation and muscle degeneration, has Caenorhabditis elegans and human homologues. In these highly conserved genes, two previously known gene families have been brought together, families encoding the actin-binding proteins related to gelsolin and the leucine-rich-repeat (LRR) group of proteins involved in protein-protein interactions. Both these gene families exhibit characteristics of molecular changes involving replication slippage and exon shuffling. Phylogenetic analyses of 19 amino acid sequences of 6 related protein types indicate that actin-associated proteins related to gelsolin are monophyletic to a common ancestor and include flightless proteins. Conversely, comparison of 24 amino acid sequences of LRR proteins including the flightless proteins indicates that flightless proteins are members of a structurally related subgroup. Included in the flightless cluster are human and mouse rsp-1 proteins involved in suppressing v-Ras transformation of cells and the membrane-associated yeast (Saccharomyces cerevisae) adenylate cyclase whose analogous LRRs are required for interaction with Ras proteins. There is a strong possibility that ligands for this group could be related and that flightless may have a similar role in Ras signal transduction. It is hypothesized that an ancestral monomeric gelsolin precursor protein has undergone at least four independent gene reorganization events to account for the structural diversity of the extant family of gelsolin-related proteins and that gene duplication and exon shuffling events occurred prior to or at the beginning of multicellular life, resulting in the evolution of some members of the family soon after the appearance of actin-type proteins.}, } @article {pmid7731978, year = {1995}, author = {Suzuki, JY and Bauer, CE}, title = {A prokaryotic origin for light-dependent chlorophyll biosynthesis of plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {92}, number = {9}, pages = {3749-3753}, pmid = {7731978}, issn = {0027-8424}, support = {R01 GM053940/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Chlorophyll/*biosynthesis ; Cloning, Molecular ; Cosmids ; Cyanobacteria/enzymology/genetics ; Gene Library ; Genetic Complementation Test ; Light ; Molecular Sequence Data ; Open Reading Frames ; Oxidoreductases/*biosynthesis/chemistry/metabolism ; *Oxidoreductases Acting on CH-CH Group Donors ; Plants/*enzymology/genetics ; Plasmids ; Recombinant Proteins/biosynthesis/chemistry ; Restriction Mapping ; Rhodobacter capsulatus/enzymology/genetics ; Sequence Homology, Amino Acid ; }, abstract = {Flowering plants require light for chlorophyll synthesis. Early studies indicated that the dependence on light for greening stemmed in part from the light-dependent reduction of the chlorophyll intermediate protochlorophyllide to the product chlorophyllide. Light-dependent reduction of protochlorophyllide by flowering plants is contrasted by the ability of nonflowering plants, algae, and photosynthetic bacteria to reduce protochlorophyllide and, hence, synthesize (bacterio) chlorophyll in the dark. In this report, we functionally complemented a light-independent protochlorophyllide reductase mutant of the eubacterium Rhodobacter capsulatus with an expression library composed of genomic DNA from the cyanobacterium Synechocystis sp. PCC 6803. The complemented R. capsulatus strain is capable of synthesizing bacteriochlorophyll in the light, thereby indicating that a chlorophyll biosynthesis enzyme can function in the bacteriochlorophyll biosynthetic pathway. However, under dark growth conditions the complemented R. capsulatus strain fails to synthesize bacteriochlorophyll and instead accumulates protochlorophyllide. Sequence analysis demonstrates that the complementing Synechocystis genomic DNA fragment exhibits a high degree of sequence identity (53-56%) with light-dependent protochlorophyllide reductase enzymes found in plants. The observation that a plant-type, light-dependent protochlorophyllide reductase enzyme exists in a cyanobacterium indicates that light-dependent protochlorophyllide reductase evolved before the advent of eukaryotic photosynthesis. As such, this enzyme did not arise to fulfill a function necessitated either by the endosymbiotic evolution of the chloroplast or by multicellularity; rather, it evolved to fulfill a fundamentally cell-autonomous role.}, } @article {pmid7648513, year = {1995}, author = {Chagoya de Sánchez, V}, title = {Circadian variations of adenosine and of its metabolism. Could adenosine be a molecular oscillator for circadian rhythms?.}, journal = {Canadian journal of physiology and pharmacology}, volume = {73}, number = {3}, pages = {339-355}, doi = {10.1139/y95-044}, pmid = {7648513}, issn = {0008-4212}, mesh = {Adenosine/metabolism/*physiology ; Animals ; Circadian Rhythm/*physiology ; Humans ; }, abstract = {The present review describes the biological implications of the periodic changes of adenosine concentrations in different tissues of the rat. Adenosine is a purine molecule that could have been formed in the prebiotic chemical evolution and has been preserved. The rhythmicity of this molecule, as well as its metabolism and even the presence of specific receptors, suggests a regulatory role in eukaryotic cells and in multicellular organisms. Adenosine may be considered a chemical messenger and its action could take place at the level of the same cell (autocrine), the same tissue (paracrine), or on separate organs (endocrine). Exploration of the circadian variations of adenosine was planned considering the liver as an important tissue for purine formation, the blood as a vehicle among tissues, and the brain as the possible acceptor for hepatic adenosine or its metabolites. The rats used in these studies were adapted to a dark-light cycle of 12 h with an unrestrained feeding and drinking schedule. The metabolic control of adenosine concentration in the different tissues studied through the 24-h cycle is related to the activity of adenosine-metabolizing enzyme: 5'-nucleotidase adenosine deaminase, adenosine kinase, and S-adenosylhomocysteine hydrolase. Some possibilities of the factors modulating the activity of these enzymes are commented upon. The multiphysiological action of adenosine could be mediated by several actions: (i) by interaction with extracellular and intracellular receptors and (ii) through its metabolism modulating the methylation pathway, possibly inducing physiological lipoperoxidation, or participating in the energetic homeostasis of the cell. The physiological meaning of the circadian variations of adenosine and its metabolism was focused on: maintenance of the energetic homeostasis of the tissues, modulation of membrane structure and function, regulation of fasting and feeding metabolic pattern, and its participation in the sleep-wake cycle. From these considerations, we suggest that adenosine could be a molecular oscillator involved in the circadian pattern of biological activity in the rat.}, } @article {pmid7548839, year = {1995}, author = {Bellamy, CO and Malcomson, RD and Harrison, DJ and Wyllie, AH}, title = {Cell death in health and disease: the biology and regulation of apoptosis.}, journal = {Seminars in cancer biology}, volume = {6}, number = {1}, pages = {3-16}, doi = {10.1006/scbi.1995.0002}, pmid = {7548839}, issn = {1044-579X}, mesh = {Acquired Immunodeficiency Syndrome/pathology ; Animals ; Apoptosis/*physiology ; Cell Death/physiology ; Humans ; Inflammation/pathology ; Neoplasms/pathology ; Neoplasms, Experimental/pathology ; }, abstract = {Apoptosis is a morphologically stereotyped form of cell death, prevalent in multicellular organisms, by which single cells are deleted from the midst of living tissues. Recognition of the cellular corpses and their removal by phagocytosis occurs without disturbance to tissue architecture or function and without initiating inflammation. Apoptosis is regulable and is of fundamental importance to tissue development and homeostasis. Cellular susceptibility to apoptosis is determined by a variety of signals, of both extracellular and internal origin, including proliferative status. Dysregulated apoptosis is important in the pathogenesis of several important human diseases including neoplasia, and recognition of the defects involved is prompting development of new therapeutic strategies.}, } @article {pmid7898582, year = {1995}, author = {Müller, WE and Müller, IM and Rinkevich, B and Gamulin, V}, title = {Molecular evolution: evidence for the monophyletic origin of multicellular animals.}, journal = {Die Naturwissenschaften}, volume = {82}, number = {1}, pages = {36-38}, pmid = {7898582}, issn = {0028-1042}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Eukaryota/genetics ; Galectins ; Hemagglutinins/*genetics ; Invertebrates/classification/genetics ; Molecular Sequence Data ; Phylogeny ; Porifera/*genetics ; Proteins/*genetics ; Vertebrates/classification/genetics ; }, } @article {pmid7663475, year = {1995}, author = {Vinnikov, IaA}, title = {[Gravitational mechanisms of interactions of sensory systems in invertebrates in the evolutionary aspect].}, journal = {Aviakosmicheskaia i ekologicheskaia meditsina = Aerospace and environmental medicine}, volume = {29}, number = {1}, pages = {4-19}, pmid = {7663475}, issn = {0233-528X}, mesh = {Animals ; *Biological Evolution ; *Gravitation ; Invertebrates/*physiology ; Locomotion ; *Nervous System Physiological Phenomena ; Sensation/*physiology ; Sensory Receptor Cells/physiology ; }, abstract = {The paper concerns the origin and the interaction of sensory organs in the context of locomotion. The Earth's gravity, light, sound, electrical, mechanical, etc. impacts were the morphogenetic factors of evolution which pushed the gene to elaborate adequate mechanisms for surmounting gravity, i.e. for exercising directed locomotion. Indeed, even some species of bacteria have mobile levers, flagelli. As a rule, the flagellum itself is the carrier of protein sensory molecules perceiving gravity as a mechanic stress, light, chemical ligands, sound, electricity, etc. On the molecular, subcellular, cellular, and organic levels in unicells and most ancient multicellular organisms an attempt has been made to follow the evolution of locomotion substrate and sensory organs and nerve centers interacting with the substrate and each other and, taken together, recognized as the locomotor-sensory system (LMSS).}, } @article {pmid7599278, year = {1995}, author = {Lane, BG and Ofengand, J and Gray, MW}, title = {Pseudouridine and O2'-methylated nucleosides. Significance of their selective occurrence in rRNA domains that function in ribosome-catalyzed synthesis of the peptide bonds in proteins.}, journal = {Biochimie}, volume = {77}, number = {1-2}, pages = {7-15}, doi = {10.1016/0300-9084(96)88098-9}, pmid = {7599278}, issn = {0300-9084}, mesh = {Base Sequence ; Biological Evolution ; Methylation ; Molecular Sequence Data ; *Peptide Biosynthesis ; Pseudouridine/*analysis/chemistry/metabolism ; RNA, Catalytic/*chemistry/metabolism ; RNA, Ribosomal/*chemistry/metabolism ; RNA, Small Nuclear/chemistry ; RNA, Transfer/chemistry ; Ribonucleosides/*analysis ; Ribosomes/*metabolism ; }, abstract = {Pseudouridine (5-ribosyluracil, psi) was the first of a host of modified nucleoside constituents detected in cellular RNA and it remains the most abundant, being broadly distributed in the RNA of archaebacteria, eubacteria and eukaryotes. Like some other modifications, psi is particularly abundant in more complex organisms, reaching 2-3% of the total nucleoside constituents in tRNA, snRNA and rRNA of multicellular plants and animals. Like all other modified nucleosides, psi arises by site-specific, enzymically catalyzed modification of a nucleoside residue in an RNA molecule. Unlike all other modified nucleosides, psi arises by isomerisation (not substitution) of a classical nucleoside, uridine (1-ribosyluracil). There have been suggestions that key processes such as ribosome assembly and peptidyl transfer may rely, more than is generally appreciated, on RNA modifications such as O2'-methylation and pseudouridylation, respectively. However, a persuasive case for the view that secondary modifications are of primary importance in ribosome function has not been convincingly made. Accordingly, we think it is timely to broaden what is generally meant by the 'catalytic properties of rRNA', and to ask, to what extent do modifications contribute to in vivo rates of ribosome assembly and ribosomal peptide-bond synthesis? The first part of this article sets forth the evidence that there is a conspicuous association between modified nucleosides and cellular RNAs that participate in group-transfer reactions. The second part reviews evidence in support of the view that the functions of psi and other modified nucleosides are likely of central importance for understanding the dynamics and stereostructural modeling at functionally significant sites in the ribosome.}, } @article {pmid7813418, year = {1994}, author = {Feldmann, H and Aigle, M and Aljinovic, G and André, B and Baclet, MC and Barthe, C and Baur, A and Bécam, AM and Biteau, N and Boles, E and Brandt, T and Brendel, M and Brückner, M and Bussereau, F and Christiansen, C and Contreras, R and Crouzet, M and Cziepluch, C and Démolis, N and Delaveau, T and Doignon, F and Domdey, H and Düsterhus, S and Dubois, E and Dujon, B and El Bakkoury, M and Entian, KD and Feurmann, M and Fiers, W and Fobo, GM and Fritz, C and Gassenhuber, H and Glandsdorff, N and Goffeau, A and Grivell, LA and de Haan, M and Hein, C and Herbert, CJ and Hollenberg, CP and Holmstrøm, K and Jacq, C and Jacquet, M and Jauniaux, JC and Jonniaux, JL and Kallesøe, T and Kiesau, P and Kirchrath, L and Kötter, P and Korol, S and Liebl, S and Logghe, M and Lohan, AJ and Louis, EJ and Li, ZY and Maat, MJ and Mallet, L and Mannhaupt, G and Messenguy, F and Miosga, T and Molemans, F and Müller, S and Nasr, F and Obermaier, B and Perea, J and Piérard, A and Piravandi, E and Pohl, FM and Pohl, TM and Potier, S and Proft, M and Purnelle, B and Ramezani Rad, M and Rieger, M and Rose, M and Schaaff-Gerstenschläger, I and Scherens, B and Schwarzlose, C and Skala, J and Slonimski, PP and Smits, PH and Souciet, JL and Steensma, HY and Stucka, R and Urrestarazu, A and van der Aart, QJ and van Dyck, L and Vassarotti, A and Vetter, I and Vierendeels, F and Vissers, S and Wagner, G and de Wergifosse, P and Wolfe, KH and Zagulski, M and Zimmermann, FK and Mewes, HW and Kleine, K}, title = {Complete DNA sequence of yeast chromosome II.}, journal = {The EMBO journal}, volume = {13}, number = {24}, pages = {5795-5809}, pmid = {7813418}, issn = {0261-4189}, mesh = {Base Composition ; Base Sequence ; Chromosome Mapping/*methods ; Chromosomes, Fungal/*genetics ; Cloning, Molecular ; Cosmids/genetics ; DNA, Fungal/*genetics ; Genes, Fungal/*genetics ; Molecular Sequence Data ; Open Reading Frames ; Quality Control ; Repetitive Sequences, Nucleic Acid ; Reproducibility of Results ; Saccharomyces cerevisiae/*genetics ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Telomere/genetics ; }, abstract = {In the framework of the EU genome-sequencing programmes, the complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome II (807 188 bp) has been determined. At present, this is the largest eukaryotic chromosome entirely sequenced. A total of 410 open reading frames (ORFs) were identified, covering 72% of the sequence. Similarity searches revealed that 124 ORFs (30%) correspond to genes of known function, 51 ORFs (12.5%) appear to be homologues of genes whose functions are known, 52 others (12.5%) have homologues the functions of which are not well defined and another 33 of the novel putative genes (8%) exhibit a degree of similarity which is insufficient to confidently assign function. Of the genes on chromosome II, 37-45% are thus of unpredicted function. Among the novel putative genes, we found several that are related to genes that perform differentiated functions in multicellular organisms of are involved in malignancy. In addition to a compact arrangement of potential protein coding sequences, the analysis of this chromosome confirmed general chromosome patterns but also revealed particular novel features of chromosomal organization. Alternating regional variations in average base composition correlate with variations in local gene density along chromosome II, as observed in chromosomes XI and III. We propose that functional ARS elements are preferably located in the AT-rich regions that have a spacing of approximately 110 kb. Similarly, the 13 tRNA genes and the three Ty elements of chromosome II are found in AT-rich regions. In chromosome II, the distribution of coding sequences between the two strands is biased, with a ratio of 1.3:1. An interesting aspect regarding the evolution of the eukaryotic genome is the finding that chromosome II has a high degree of internal genetic redundancy, amounting to 16% of the coding capacity.}, } @article {pmid7998996, year = {1994}, author = {Combettes, L and Tran, D and Tordjmann, T and Laurent, M and Berthon, B and Claret, M}, title = {Ca(2+)-mobilizing hormones induce sequentially ordered Ca2+ signals in multicellular systems of rat hepatocytes.}, journal = {The Biochemical journal}, volume = {304 (Pt 2)}, number = {Pt 2}, pages = {585-594}, pmid = {7998996}, issn = {0264-6021}, mesh = {Animals ; Bile Canaliculi/ultrastructure ; Calcium/*metabolism ; Connexins/immunology ; Female ; Fura-2 ; Gap Junctions/drug effects/*physiology ; Image Processing, Computer-Assisted ; Liver/drug effects/*metabolism/ultrastructure ; Microscopy, Fluorescence ; Norepinephrine/*pharmacology ; Rats ; Rats, Wistar ; Vasopressins/*pharmacology ; }, abstract = {The development of hormone-mediated Ca2+ signals was analysed in polarized doublets, triplets and quadruplets of rat hepatocytes by video imaging of fura2 fluorescence. These multicellular models showed dilated bile canaliculi, and gap junctions were observed by using an anti-connexin-32 antibody. They also showed highly organized Ca2+ signals in response to vasopressin or noradrenaline. Surprisingly, the primary rises in intracellular Ca2+ concentration ([Ca2+]i) did not start randomly from any cell of the multiplet. It originated invariably in the same hepatocyte (first-responding cell), and then was propagated in a sequential manner to the nearest connected cells (cell 2, then 3, in triplets; cell 2, 3, then 4 in quadruplets). The sequential activation of the cells appeared to be an intrinsic property of multiplets of rat hepatocytes. (1) In the continued presence of hormones, the same sequential order was observed up to six times, i.e. at each train of oscillations occurring between the cells. (2) The order of [Ca2+]i responses was modified neither by the repeated addition of hormones nor by the hormonal dose. (3) The mechanical disruption of an intermediate cell slowed down the speed of the propagation, suggesting a role of gap junctions in the rapidity of the sequential activation of cells. (4) The same multiplet could have a different first-responding cell for vasopressin or noradrenaline, suggesting a role of the hormonal receptors in the sequentiality of cell responses. It is postulated that a functional heterogeneity of hormonal receptors, and the presence of functional gap junctions, are involved in the existence of sequentially ordered hormone-mediated [Ca2+]i rises in the multiplets of rat hepatocytes.}, } @article {pmid7896314, year = {1994}, author = {Singh, N and Anand, S}, title = {Cell death by apoptosis.}, journal = {Indian journal of experimental biology}, volume = {32}, number = {12}, pages = {843-847}, pmid = {7896314}, issn = {0019-5189}, mesh = {Apoptosis/*physiology ; Cell Communication/physiology ; Gene Expression/physiology ; Humans ; }, abstract = {Apoptosis has been the focus of considerable attention in recent years. Apoptosis/programmed cell death, is a morphologically distinct process of cell death in which cells die in a controlled manner, in response to specific stimuli, following an intrinsic programme. Apoptosis is a greek work which means "falling off", as of leaves from trees. So occurs in plants suggesting that apoptosis originated very early in biological evolution. This wide spread active process of self destruction is seen in a wide variety of tissues, and is an essential feature in both development and maintenance of multicellular animals. It is ascribed roles in the process of embryogenesis, differentiation, metamorphosis, neural development, epithelial turnover, aging, regulation of cell population of the immune system and tumor regression.}, } @article {pmid7888751, year = {1994}, author = {Mattick, JS}, title = {Introns: evolution and function.}, journal = {Current opinion in genetics & development}, volume = {4}, number = {6}, pages = {823-831}, doi = {10.1016/0959-437x(94)90066-3}, pmid = {7888751}, issn = {0959-437X}, mesh = {Animals ; *Biological Evolution ; Eukaryotic Cells/chemistry ; *Introns/genetics/physiology ; RNA Splicing ; RNA, Catalytic/*genetics ; RNA, Small Nuclear/genetics ; Retroelements ; }, abstract = {The debate continues on the issue of whether nuclear introns were present in eukaryotic protein-coding genes from the beginning (introns-early) or invaded them later in evolution (introns-late). Recent studies concerning the location of introns with respect to gene and protein structure have been interpreted as providing strong support for both positions, but the weight of argument is clearly moving in favour of the latter. Consistent with this, there is now good evidence that introns can function as transposable elements, and that nuclear introns derived from self-splicing group II introns, which then evolved in partnership with the spliceosome. This was only made possible by the separation of transcription and translation. If introns did colonize eukaryotic genes after their divergence from prokaryotes, the original question as to the evolutionary forces that have seen these sequences flourish in the higher organisms, and their significance in eukaryotic biology, is again thrown open. I suggest that introns, once established in eukaryotic genomes, might have explored new genetic space and acquired functions which provided a positive pressure for their expansion. I further suggest that there are now two types of information produced by eukaryotic genes--mRNA and iRNA--and that this was a critical step in the development of multicellular organisms.}, } @article {pmid7708828, year = {1994}, author = {Ewald, PW}, title = {Evolution of mutation rate and virulence among human retroviruses.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {346}, number = {1317}, pages = {333-41; discussion 341-3}, doi = {10.1098/rstb.1994.0150}, pmid = {7708828}, issn = {0962-8436}, mesh = {Biological Evolution ; Humans ; Mutation ; Retroviridae/*genetics/*pathogenicity ; Virulence ; }, abstract = {High mutation rates are generally considered to be detrimental to the fitness of multicellular organisms because mutations untune finely tuned biological machinery. However, high mutation rates may be favoured by a need to evade an immune system that has been strongly stimulated to recognize those variants that reproduced earlier during the infection. HIV infections conform to this situation because they are characterized by large numbers of viruses that are continually breaking latency and large numbers that are actively replicating throughout a long period of infection. To be transmitted, HIVs are thus generally exposed to an immune system that has been activated to destroy them in response to prior viral replication in the individual. Increases in sexual contact should contribute to this predicament by favouring evolution toward relatively high rates of replication early during infection. Because rapid replication and high mutation rate probably contribute to rapid progression of infections to AIDS, the interplay of sexual activity, replication rate, and mutation rate helps explain why HIV-1 has only recently caused a lethal pandemic, even though molecular data suggest that it may have been present in humans for more than a century. This interplay also offers an explanation for geographic differences in progression to cancer found among infections due to the other major group of human retroviruses, human T-cell lymphotropic viruses (HTLV). Finally, it suggests ways in which we can use natural selection as a tool to control the AIDS pandemic and prevent similar pandemics from arising in the future.}, } @article {pmid7525326, year = {1994}, author = {Kruk, PA and Uitto, VJ and Firth, JD and Dedhar, S and Auersperg, N}, title = {Reciprocal interactions between human ovarian surface epithelial cells and adjacent extracellular matrix.}, journal = {Experimental cell research}, volume = {215}, number = {1}, pages = {97-108}, doi = {10.1006/excr.1994.1320}, pmid = {7525326}, issn = {0014-4827}, mesh = {Adult ; Aged ; Amino Acid Sequence ; Blotting, Northern ; Cell Aggregation ; Cells, Cultured ; Collagen/analysis ; Drug Combinations ; Endopeptidases/analysis ; Epithelial Cells ; Epithelium/physiology/ultrastructure ; Extracellular Matrix/*physiology/ultrastructure ; Extracellular Matrix Proteins/*analysis/physiology ; Female ; Fibrin ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Integrins/biosynthesis/isolation & purification ; Keratins/analysis ; Laminin/analysis ; Microscopy, Electron, Scanning ; Middle Aged ; Molecular Sequence Data ; Ovary/cytology/*physiology ; Ovulation ; Plasminogen Activator Inhibitor 1/analysis ; Plastics ; Proteoglycans ; RNA/analysis ; Receptors, Cytoadhesin/biosynthesis/isolation & purification ; Receptors, Vitronectin ; Substrate Specificity ; }, abstract = {The human ovarian surface epithelium (OSE), or ovarian mesothelium, is functionally complex as seen by its capacity to proliferate, migrate, and contribute to ovulation and ovulatory repair in response to cyclic hormonal and environmental changes. We wished to determine whether this phenotypic versatility is reflected in cell-extracellular matrix interactions in primary and low-passage culture. Comparisons of cultures maintained on different substrata revealed that these cells form cohesive monolayers on plastic, while fibrin clots enhance cell dispersion, and thus may provide a migratory cue. The cells invaded Matrigel as multicellular aggregates, while collagen gels mediated a morphologic epithelial-mesenchymal conversion. On plastic, the cells produced extracellular matrix components characteristic of epithelial basement membrane (laminin and collagen type IV), as well as stroma (collagen types I and III). In addition, ovarian surface epithelial cells secreted serine proteases and matrix metalloproteinases. The levels of chymotrypsin- and elastase-like proteases were dictated by the substratum: low levels were secreted by cells grown on plastic, intermediate levels on collagen gels and fibrin clots, and most protease was produced on Matrigel. The rate of cell proliferation varied with the substrata and was inversely related to protease secretion. Integrin expression was greatest on plastic and least on collagen gels where integrins were downregulated with time. alpha 6/beta 4 was absent from all cells while varying levels of alpha 2, alpha 3, alpha 5, beta 1, and vitronectin receptor were detected depending on the culture substratum employed. In low-passage cultures of human ovarian surface epithelial cells, then, cell shape, growth, protease production, and integrin expression are modulated by the extracellular matrix. The cells, in turn, alter extracellular matrix by synthesis, lysis, and physical remodeling, and express both stromal and epithelial characteristics. The broad repertoire of these functions may be related to their mesodermal origin, and may reflect the expression of a dual, epithelio-mesenchymal phenotype by relatively immature, uncommitted cells. The results demonstrate the great complexity and versatility of these interactions which render OSE cells capable of participating in numerous physiological and pathological processes.}, } @article {pmid7996858, year = {1994}, author = {Jablonka, E}, title = {Inheritance systems and the evolution of new levels of individuality.}, journal = {Journal of theoretical biology}, volume = {170}, number = {3}, pages = {301-309}, doi = {10.1006/jtbi.1994.1191}, pmid = {7996858}, issn = {0022-5193}, mesh = {Animals ; *Biological Evolution ; Cell Adhesion ; Cell Aggregation ; Cell Physiological Phenomena ; *Extrachromosomal Inheritance ; Species Specificity ; }, abstract = {Evolutionary transitions to new levels of individuality have usually been treated as a part of the "units of selection" problem. It has previously been assumed that the unit of transmission and heritable variation at each level is the same--that it is the DNA base sequence and its variations. It is suggested here that considering the nature and the role of hereditary variations produced by non-DNA inheritance systems is essential for understanding some evolutionary transitions. The argument is illustrated by considering the role of epigenetic inheritance systems (EISs), the systems responsible for cellular memory, in the transition from unicellularity to multicellularity. It is argued that EISs played a vital role in the transition to multicellularity and the evolution of complex ontogenies, as well as having an important effect on the evolution of developmental strategies which protect the multicellular individual from disintegrating into its component parts. An analogy between the transition to multicellularity and the transition to a cultural unit integrated by language is also suggested.}, } @article {pmid7966367, year = {1994}, author = {Müller, WE and Schröder, HC and Müller, IM and Gamulin, V}, title = {Phylogenetic relationship of ubiquitin repeats in the polyubiquitin gene from the marine sponge Geodia cydonium.}, journal = {Journal of molecular evolution}, volume = {39}, number = {4}, pages = {369-377}, pmid = {7966367}, issn = {0022-2844}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Biological Evolution ; DNA/genetics ; Molecular Sequence Data ; Mutation ; Phylogeny ; Porifera ; *Repetitive Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Ubiquitins/*genetics ; }, abstract = {Ubiquitin is a 76-residue protein which is highly conserved among eukaryotes. Sponge (Porifera) ubiquitin, isolated from Geodia cydonium, is encoded by a gene (termed GCUBI) with six repeats, GCUBI-1 to GCUBI-6. All repeat units encode the same protein (with one exception: GCUBI-4 encodes ubiquitin with a change of Leu to Val at position 71). On the nt level the sequences of the six repeats differ considerably. All changes (except in GCUBI-4) are silent substitutions, which do not affect the protein structure. However, there is one major difference between the repeats: Codons from both codon families (TCN and AGPy) are simultaneously used for the serine at position 65. Using this characteristic the repeats were divided into two groups: Group I: GCUBI-1,3 (TCT codon) and GCUBI-5 (TCC); Group II: GCUBI-2,4,6 (AGC codon). Mutational analysis suggests that the sponge polyubiquitin gene evolved from an ancestral monoubiquitin gene by gene duplication and successive tandem duplications. The ancestral monoubiquitin gene most probably coded for threonine (ACC) at position 65. The first event, duplication of the monoubiquitin gene, happened some 110 million years ago. Since sponges from the genus Geodia are known from the Cretaceous (145 million) to recent time, it is very likely that all events in the evolution of polyubiquitin gene occurred in the same genus. Alignment data of the "consensus" ubiquitin nt sequences of different animals (man to protozoa) reflect very well the established phylogenetic relationships of the chosen organisms and show that the sponge ubiquitin gene branched off first from the multicellular organisms.}, } @article {pmid7923079, year = {1994}, author = {Gorunova, L and Mertens, F and Mandahl, N and Jonsson, N and Persson, B and Heim, S and Mitelman, F}, title = {Cytogenetic heterogeneity in a clear cell hidradenoma of the skin.}, journal = {Cancer genetics and cytogenetics}, volume = {77}, number = {1}, pages = {26-32}, doi = {10.1016/0165-4608(94)90144-9}, pmid = {7923079}, issn = {0165-4608}, mesh = {Acrospiroma/*genetics/pathology ; Aged ; *Chromosome Aberrations ; Humans ; Karyotyping ; Male ; Skin Neoplasms/*genetics/pathology ; }, abstract = {Short-term cultures from a clear cell hidradenoma, a benign skin tumor for which no chromosome data exist, were cytogenetically analyzed. A total of eight unrelated aberrant clones were identified. The karyotypic profiles of two separately processed parts of the sample--a tumor nodule and seemingly normal adjacent dermal tissue--were different. Characteristic for the tumor nodule was a single abnormal clonal population consisting of three subclones: 46,XY,der(2)inv(2)(p13q23)t(2;9)(p13;q22), der(9)t(2;9)(q23;q22),t(11;19)(q21;p13),t(12;19)(q24;p13)/46,idem, inv(1)(p32q44)/92,idemx2. The adjacent tissue contained, in addition to the clone found in the tumor nodule, a spectrum of unrelated clones, the largest of which also showed clonal evolution: 45-47,XY,t(3;6)(p25;p25),t(12;17)(q15;q12),-17,+r(17)x2 [cp]/45-47,idem,inv(5)(p15q22)/90-94,idemx2. The remaining six clones found in this part were small and had simpler numerical or structural aberrations. The multiclonal pattern observed in this hidradenoma seems to reflect both cytogenetic convergence and divergence during neoplastic progression. The presence of unrelated clones may be an indication that the tumor was of multicellular origin.}, } @article {pmid7876338, year = {1994}, author = {Cornillon, S and Foa, C and Davoust, J and Buonavista, N and Gross, JD and Golstein, P}, title = {Programmed cell death in Dictyostelium.}, journal = {Journal of cell science}, volume = {107 (Pt 10)}, number = {}, pages = {2691-2704}, doi = {10.1242/jcs.107.10.2691}, pmid = {7876338}, issn = {0021-9533}, mesh = {Animals ; Apoptosis/*physiology ; Biological Evolution ; Cell Differentiation/physiology ; Cell Division/physiology ; Cell Membrane Permeability/*physiology ; Chromatin/ultrastructure ; DNA, Fungal/ultrastructure ; Dictyostelium/*cytology/ultrastructure ; Vacuoles/ultrastructure ; }, abstract = {Programmed cell death (PCD) of Dictyostelium discoideum cells was triggered precisely and studied quantitatively in an in vitro system involving differentiation without morphogenesis. In temporal succession after the triggering of differentiation, PCD included first an irreversible step leading to the inability to regrow at 8 hours. At 12 hours, massive vacuolisation was best evidenced by confocal microscopy, and prominent cytoplasmic condensation and focal chromatin condensation could be observed by electron microscopy. Membrane permeabilization occurred only very late (at 40-60 hours) as judged by propidium iodide staining. No early DNA fragmentation could be detected by standard or pulsed field gel electrophoresis. These traits exhibit some similarity to those of previously described non-apoptotic and apoptotic PCD, suggesting the hypothesis of a single core molecular mechanism of PCD emerging in evolution before the postulated multiple emergences of multicellularity. A single core mechanism would underly phenotypic variations of PCD resulting in various cells from differences in enzymatic equipment and mechanical constraints. A prediction is that some of the molecules involved in the core PCD mechanism of even phylogenetically very distant organisms, e.g. Dictyostelium and vertebrates, should be related.}, } @article {pmid8090766, year = {1994}, author = {Thompson-Stewart, D and Karpen, GH and Spradling, AC}, title = {A transposable element can drive the concerted evolution of tandemly repetitious DNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {91}, number = {19}, pages = {9042-9046}, pmid = {8090766}, issn = {0027-8424}, support = {/HHMI/Howard Hughes Medical Institute/United States ; GM27875/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; *DNA Transposable Elements ; Drosophila melanogaster/*genetics ; Gene Conversion ; *Repetitive Sequences, Nucleic Acid ; }, abstract = {Recombination and conversion have been proposed to drive the concerted evolution of tandemly repeated DNA sequences. However, specific correction events within the repeated genes of multicellular organisms have not been observed directly, so their nature has remained speculative. We investigated whether the excision of transposable P elements from tandemly repeated sequences would induce unequal gene conversion. Genetically marked elements located in a subtelomeric repeat were mobilized, and the structure of the region was analyzed in progeny. We observed that the number of repeats was frequently altered. Decreases were more common than increases, and this bias probably resulted from intrinsic mechanisms governing P element-induced double-strand break repair. Our results suggest that transposable elements play an important role in the evolution of repetitious DNA.}, } @article {pmid8078481, year = {1994}, author = {Prade, RA and Timberlake, WE}, title = {The Penicillium chrysogenum and Aspergillus nidulans wetA developmental regulatory genes are functionally equivalent.}, journal = {Molecular & general genetics : MGG}, volume = {244}, number = {5}, pages = {539-547}, pmid = {8078481}, issn = {0026-8925}, support = {GM37886/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Aspergillus nidulans/*genetics/physiology ; Base Sequence ; Conserved Sequence ; DNA Mutational Analysis ; DNA Primers ; DNA, Fungal/genetics ; Fungal Proteins/chemistry/genetics ; *Gene Expression Regulation, Fungal ; *Genes, Fungal ; Genes, Regulator ; Molecular Sequence Data ; Morphogenesis ; Penicillium chrysogenum/*genetics/physiology ; Phylogeny ; Promoter Regions, Genetic ; Spores, Fungal/cytology/*growth & development ; }, abstract = {Aspergillus nidulans and Penicillium chrysogenum are related fungi that reproduce asexually by forming multicellular conidiophores and uninucleate conidia. In A. nidulans, spore maturation is controlled by the wetA (AwetA) regulatory gene. We cloned a homologous gene (PwetA) from P. chrysogenum to determine if spore maturation is regulated by a similar mechanism in this species. The PwetA and AwetA genes are similar in structure and functional organization. The inferred polypeptides share 77% overall amino acid sequence similarity, with several regions having > 85% similarity. The genes also had significant, local sequence similarities in their 5' flanking regions, including conserved binding sites for the product of the regulatory gene abaA. PwetA fully complemented an A. nidulans wetA deletion mutation, demonstrating that PwetA and its 5' regulatory sequences function normally in A. nidulans. These results indicate that the mechanisms controlling sporulation in A. nidulans and P. chrysogenum are evolutionarily conserved.}, } @article {pmid7840899, year = {1994}, author = {Gamulin, V and Rinkevich, B and Schäcke, H and Kruse, M and Müller, IM and Müller, WE}, title = {Cell adhesion receptors and nuclear receptors are highly conserved from the lowest metazoa (marine sponges) to vertebrates.}, journal = {Biological chemistry Hoppe-Seyler}, volume = {375}, number = {9}, pages = {583-588}, doi = {10.1515/bchm3.1994.375.9.583}, pmid = {7840899}, issn = {0177-3593}, mesh = {Amino Acid Sequence ; Animals ; Cell Adhesion Molecules/*metabolism ; Conserved Sequence ; Galectins ; Hemagglutinins/chemistry/genetics ; Lectins/chemistry/*genetics ; Mammals ; Molecular Sequence Data ; Porifera/*genetics ; Protein-Tyrosine Kinases/genetics ; Receptors, Cell Surface/chemistry/*genetics ; Receptors, Cytoplasmic and Nuclear/chemistry/*genetics ; Sequence Homology, Amino Acid ; Vertebrates/*metabolism ; }, abstract = {The shift from unicellular life to multicellular, integrated organisms has been accompanied by the acquisition of adhesion proteins/receptors. Recently we succeeded to clone some genes coding for such proteins from the lowest multicellular animals, the marine sponges (model: the siliceous sponge Geodia cydonium). G. cydonium contains e.g. several lectins; cDNAs for two of them were cloned. Both lectins have a framework sequence of 38 conserved amino acids which are characteristic for the carbohydrate binding site of vertebrate S-type lectins. Next, the cDNA coding for a receptor tyrosine kinase of class II was isolated and characterized. The deduced aa sequence shows two characteristic domains; (i) the tyrosine kinase domain and (ii) an immunoglobulin-like domain. The latter part displays high homology to the vertebrate type immunoglobulin domain. This result together with the lectin data demonstrates that binding domains of such adhesion proteins are not recent achievements of higher animals but exist already in animals (sponges) which have diverged from other organisms about 800 million years ago. Considering the fact that during embryogenesis of sponges a typical anteroposterior organization pattern is seen a 'home-otic' organ-like transformation has been postulated. The subsequent search for genes provided with the homeodomain-like sequence was successful. These data support the view that the kingdom Animalia is of monophyletic origin.}, } @article {pmid7787792, year = {1994}, author = {Müller, WE and Müller, IM and Gamulin, V}, title = {On the monophyletic evolution of the metazoa.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {27}, number = {9}, pages = {2083-2096}, pmid = {7787792}, issn = {0100-879X}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; *Biological Evolution ; Cloning, Molecular ; DNA, Complementary/genetics ; Humans ; Lectins/genetics ; Molecular Sequence Data ; Porifera/*genetics ; Protein-Tyrosine Kinases/genetics ; Receptor Protein-Tyrosine Kinases/genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {1. The shift from unicellular life to multicellular, integrated organisms has been accompanied by the acquisition of adhesion proteins. Recently we succeeded in cloning some genes coding for such proteins from the lowest multicellular animals, the marine sponges (model: the siliceous sponge Geodia cydonium). 2. G. cydonium contains several lectins and cDNA for two of them (termed LECT-1 and LECT-2) was cloned. Both lectins have a framework sequence of 38 conserved amino acids which are characteristic for the carbohydrate-binding site of vertebrate S-type lectins. Next, we have isolated and characterized a cDNA coding for a receptor tyrosine kinase of class II (GCTK). The deduced amino acid sequence shows two characteristic domains: i) the tyrosine kinase domain and ii) an immunoglobulin-like domain. The latter part shows high homology to the vertebrate type immunoglobulin domain. This result, together with the lectin data, demonstrates that binding domains of such adhesion proteins are not recent achievements of higher animals but exist already in animals (sponges) which have diverged from other organisms about 800 million years ago. 3. Considering the fact that during embryogenesis of sponges a typical anteroposterior organization pattern is seen, a "homeotic" organ-like transformation has been postulated. The subsequent search for genes provided with the homeodomain sequence was successful. The deduced amino acid sequence of G. cydonium showed high homology to chicken and to the Antennapedia sequence from Drosophila melanogaster. 4. These data support the view that the kingdom Animalia is of monophyletic origin.}, } @article {pmid7803760, year = {1994}, author = {Magnuson, NS and Beck, T and Vahidi, H and Hahn, H and Smola, U and Rapp, UR}, title = {The Raf-1 serine/threonine protein kinase.}, journal = {Seminars in cancer biology}, volume = {5}, number = {4}, pages = {247-253}, pmid = {7803760}, issn = {1044-579X}, mesh = {Animals ; Calcium-Calmodulin-Dependent Protein Kinases/physiology ; Cyclic AMP-Dependent Protein Kinases/physiology ; Genes, ras ; Humans ; Protein Kinase C/physiology ; Protein Serine-Threonine Kinases/*physiology ; Proto-Oncogene Proteins/*physiology ; Proto-Oncogene Proteins c-raf ; Signal Transduction ; }, abstract = {Raf-1 belongs to a family of serine/threonine protein kinases which are highly conserved through evolution in multicellular organisms. Raf-1 kinase has gained much attention due to its function as a critical shuttle enzyme that connects stimulation of growth factor receptors and protein kinase C at the cell membrane to changes in the expression of genes involved in the control of cell growth, differentiation and survival. Regulation of Raf-1 activity is complex and involves Ras, as well as several serine/threonine and tyrosine kinases. Through a series of phosphorylation events, extracellular signals are connected through the Raf-1/MAP kinase pathway to activity-regulation of several oncogene-class transcription factors via phosphorylation of specific serine residues. Under ordinary circumstances, the cascade involving Raf-1 eventually leads to changes in gene expression and protein synthesis. Upon constitutive activation of Raf-1 kinase, as a result of genetic changes, a variety of cell types acquire a transformed phenotype.}, } @article {pmid7934077, year = {1994}, author = {Szathmáry, E}, title = {Toy models for simple forms of multicellularity, soma and germ.}, journal = {Journal of theoretical biology}, volume = {169}, number = {2}, pages = {125-132}, doi = {10.1006/jtbi.1994.1134}, pmid = {7934077}, issn = {0022-5193}, mesh = {Animals ; *Biological Evolution ; *Cell Physiological Phenomena ; Germ Cells/physiology ; Models, Biological ; *Reproduction ; }, abstract = {Simple models for the development, maintenance, and origins of primitive, one- or two-dimensional "toy organisms" are presented. They are similar to cellular automata with the added combination of internal degrees of freedom that are genetically programmed. The growing rules are implementable by cellular mechanics, biochemistry and genetics. The forms that are dealt with are: sexual unicells, filaments with fragmentation, cell doublets with spore formation, filaments with differentiation of soma and germ, and two-dimensional colonies with early segregation of somatic cells and germ line. The minimum models presented help to understand the feasibility of several important evolutionary transitions. An explanation, supported by the models, for the fact that all three multicellular kingdoms are primarily sexual, is offered by the observation that sexuality in unicells is an excellent preadaptation for development, for the former entails programmed differentiation of cell types (relying in part on the action of homeobox genes), use of cell surface molecules, programmed arrest of cell division, etc. Relevant examples of existing biological systems are also presented.}, } @article {pmid7962158, year = {1994}, author = {Parfitt, AM}, title = {Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone.}, journal = {Journal of cellular biochemistry}, volume = {55}, number = {3}, pages = {273-286}, doi = {10.1002/jcb.240550303}, pmid = {7962158}, issn = {0730-2312}, mesh = {Adult ; Bone Remodeling/*physiology ; Humans ; Osteoblasts/*physiology ; Osteoclasts/*physiology ; Signal Transduction/*physiology ; Time Factors ; }, abstract = {The bone replacement process in the adult skeleton is known as remodeling. When bone is removed by osteoclasts, new bone is laid down by osteoblasts in the same place, because the load bearing requirement is unchanged. Bone is usually replaced because it is too old to carry out its function, which is mainly mechanical in cortical bone and mainly support for homeostasis and hematopoiesis in cancellous bone. Remodeling always begins on a quiescent bone surface, separated from the marrow by flat lining cells that are one of the two modes of terminal differentiation of osteoblasts. Lining cells are gatekeepers, able to be informed of the need for remodeling, and to either execute or mediate all four components of its activation-selection and preparation of the site, recruitment of mononuclear preosteoclasts, budding of new capillaries, and attraction of preosteoclasts to the chosen site where they fuse into multinucleated osteoclasts. In cortical bone, osteonal remodeling is carried out by a complex and unique structure, the basic multicellular unit (BMU) that comprises a cutting cone of osteoclasts in front, a closing cone lined by osteoblasts following behind, and connective tissue, blood vessels and nerves filling the cavity. The BMU maintains its size, shape and internal organization for many months as it travels through bone in a controlled direction. Individual osteoclast nuclei are short-lived, turning over about 8% per d, replaced by new preosteoclasts that originated in the bone marrow and travel in the circulation to the site of resorption. Refilling of bone at each successive cross-sectional location is accomplished by a team of osteoblasts, probably originating from precursors within the local connective tissue, all assembled within a narrow window of time, at the right location, and in the right orientation to the surface. Each osteoblast team forms bone most rapidly at its onset and slows down progressively. Some of the osteoblasts are buried as osteocytes, some die, and the remainder gradually assume the shape of lining cells. Cancellous bone is more accessible to study than cortical bone, but is geometrically complex. Although remodeling conforms to the same sequence of surface activation, resorption and formation, its three-dimensional organization is difficult to visualize from two-dimensional histologic sections.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid8088865, year = {1994}, author = {Quintáns, J}, title = {Immunity and inflammation: the cosmic view.}, journal = {Immunology and cell biology}, volume = {72}, number = {3}, pages = {262-266}, doi = {10.1038/icb.1994.39}, pmid = {8088865}, issn = {0818-9641}, mesh = {Animals ; *Biological Evolution ; Immune Tolerance/immunology ; Immunity/*physiology ; Immunologic Memory ; Inflammation/*immunology ; }, abstract = {This paper presents an overview of the evolution of defence reactions in multicellular animal life. The co-evolution of hosts and pathogens provides the context to describe the major features of defence reactions and the countermeasures they evoke in their targets. Three major types of solutions to the riddle of self-non-self discrimination are discussed briefly: non-clonal recognition mediated by lectins, the preferential accumulation of C3 in microbial surfaces and vertebrate clonal immunity. Vertebrate immunity is described as a specialized type of inflammation against infectious agents that evolved in response to countermeasures successfully used by intracellular pathogens against non-specific defences.}, } @article {pmid8056318, year = {1994}, author = {Kondrashov, AS}, title = {Mutation load under vegetative reproduction and cytoplasmic inheritance.}, journal = {Genetics}, volume = {137}, number = {1}, pages = {311-318}, pmid = {8056318}, issn = {0016-6731}, support = {GM 36827/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Cytoplasm ; *Models, Genetic ; *Mutation ; Reproduction/genetics ; Selection, Genetic ; }, abstract = {For reasons that remain unclear, even multicellular organisms usually originate from a single cell. Here I consider the balance between deleterious mutations and selection against them in a population with obligate vegetative reproduction, when every offspring is initiated by more than one cell of a parent. The mutation load depends on the genomic deleterious mutation rate U, strictness of selection, number of cells which initiate an offspring n, and the relatedness among the initial cells. The load grows with increasing U, n and strictness of selection, and declines when an offspring is initiated by more closely related cells. If Un >> 1, the load under obligate vegetative reproduction may be substantially higher than under sexual or asexual reproduction, which may account for its rarity. In nature obligate vegetative reproduction seems to be more common and long term in taxa whose cytological features ensure a relatively low load under it. The same model also describes the mutation load under two other modes of inheritance: (1) uniparental transmission of organelles and (2) reproduction by division of multinuclear cells, where each daughter cell receives many nuclei. The load declines substantially when the deleterious mutation rate per organelle genome gets lower or when the number of nuclei in a cell sometimes drops. This may explain the small sizes of organelle genomes in sexual lineages and the presence of karyonic cycles in asexual unicellular multinuclear eukaryotes.}, } @article {pmid7632194, year = {1994}, author = {Opitz, JM and de la Cruz, F}, title = {Cholesterol metabolism in the RSH/Smith-Lemli-Opitz syndrome: summary of an NICHD conference.}, journal = {American journal of medical genetics}, volume = {50}, number = {4}, pages = {326-338}, doi = {10.1002/ajmg.1320500406}, pmid = {7632194}, issn = {0148-7299}, mesh = {Abnormalities, Multiple/*metabolism ; Blood-Brain Barrier ; Brain Chemistry ; Cholesterol/*biosynthesis ; Cholesterol, Dietary/therapeutic use ; Dehydrocholesterols/blood ; Face/abnormalities ; Genitalia/abnormalities ; Humans ; Infant, Newborn ; Intellectual Disability/metabolism ; Limb Deformities, Congenital ; Lipid Metabolism, Inborn Errors/*genetics ; Microcephaly/metabolism ; Myelin Sheath/physiology ; National Institutes of Health (U.S.) ; Neonatal Screening ; Oxidoreductases/*deficiency ; *Oxidoreductases Acting on CH-CH Group Donors ; Syndrome ; United States ; }, abstract = {During the evolution of multicellularity and attendant processes of development, cholesterol played a key role in the formation of the plasma membrane and outer mitochondrial membrane of every cell in the organism. Later functions include pivotal involvement in steroid, bile acid, and vitamin D metabolism and myelination of the nervous system. In the CNS myelination does not begin until the third trimester, and subcortical myelination not until after birth. The cholesterol of the cell membrane of the ovum is maternally derived. It is not known when the zygote begins making its own cholesterol during morphogenesis and histogenesis, but it must occur early to keep up with the dramatic rate of cell division in the embryo. Thus, it is a startling surprise that human embryos and fetuses apparently able to synthesize little cholesterol (because of a presumed defect of the delta 5,7-sterol, delta 7-reductase that converts 7-dehydrocholesterol (7-DHC) into cholesterol) frequently live to term and, rarely, may be so mildly affected as to attend school with only mild MR. The discovery by G. Stephen Tint and his co-workers of the apparent 7-DHC reductase deficiency makes the RSH (Smith-Lemli-Opitz) syndrome the first true metabolic malformation syndrome. A teratological animal model which has been known for 30 years now appears applicable to the RSH/SLO syndrome. A multidisciplinary NICHD conference held on September 20-21, 1993 reviewed the numerous implications of this discovery and agreed unanimously that research in this field be given highest priority in order to better understand cholesterol synthesis in the mammalian brain, cholesterol transport from mother to embryo and fetus, pre- and postnatal metabolic compensation in structure and function for a profound block in cholesterol synthesis, the nature of the blood-brain barrier for cholesterol, treatment of affected infants, children, and adults, structure and genetic specification of a 7-DHC reductase enzyme (which has never been purified!) and its evolution, the variability of the syndrome and whether it is genetically homo- or heterogeneous, the population genetics of the RSH syndrome, possible selective advantages (or disadvantages) of heterozygotes, and means of newborn screening, carrier detection, and prenatal diagnosis.}, } @article {pmid8056151, year = {1994}, author = {Parma, J and Duprez, L and Van Sande, J and Paschke, R and Tonacchera, M and Dumont, J and Vassart, G}, title = {Constitutively active receptors as a disease-causing mechanism.}, journal = {Molecular and cellular endocrinology}, volume = {100}, number = {1-2}, pages = {159-162}, doi = {10.1016/0303-7207(94)90296-8}, pmid = {8056151}, issn = {0303-7207}, mesh = {Animals ; Disease/*etiology ; GTP-Binding Proteins/physiology ; Gene Expression Regulation ; Humans ; Mice ; Models, Biological ; Models, Molecular ; Mutation ; Receptors, Cell Surface/genetics/*physiology ; *Signal Transduction ; }, abstract = {Membrane receptors have appeared early in evolution as the means for the unicellular organism to sense its environment. With the emergence of social cellular life in multicellular organisms, membrane receptors have acquired the additional functions of sensing the presence of similar cells (as in the aggregation phenomenon of Dictyostelium discoideum) (Klein et al., 1988) or the presence of the mate (Saccharomyces cerevisiae) (Cross et al., 1988), and to detect endocrine signals emitted by cells in distant tissues. As the latter function is central to homeostasis and regulation of cell growth, the downstream regulatory cascades under receptor control are the subject of intense research with implications in virtually all fields of biomedical science. The impact of the analysis of tyrosine kinase-activated cascades on our understanding of carcinogenesis is but one example of such an advance.}, } @article {pmid7920862, year = {1994}, author = {Schäcke, H and Schröder, HC and Gamulin, V and Rinkevich, B and Müller, IM and Müller, WE}, title = {Molecular cloning of a tyrosine kinase gene from the marine sponge Geodia cydonium: a new member belonging to the receptor tyrosine kinase class II family.}, journal = {Molecular membrane biology}, volume = {11}, number = {2}, pages = {101-107}, doi = {10.3109/09687689409162227}, pmid = {7920862}, issn = {0968-7688}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Biological Evolution ; Cell Membrane/enzymology ; Cloning, Molecular ; Cytosol/enzymology ; DNA, Complementary/genetics ; Molecular Sequence Data ; Molecular Weight ; Porifera/*enzymology/*genetics ; Protein-Tyrosine Kinases/*genetics ; RNA, Messenger/genetics ; Receptor Protein-Tyrosine Kinases/chemistry/classification/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {We have isolated and characterized a cDNA from the marine sponge Geodia cydonium coding for a new member of the tyrosine protein kinase (TK) family. The cDNA encodes a protein of M(r) = 68,710, termed GCTK, which is homologous to class II receptor tyrosine kinases (RTKs). GCTK contains conserved amino acids (aa) characteristic of all protein kinases, and the sequences DLATRN and PIRWMATE which are highly specific for TKs. Furthermore, the sequence N-L-Y-x(3)-Y-Y-R is highly homologous to the sequence D-[LIV]-Y-x(3)-Y-Y-R found only in class II RTKs. The sponge TK, when compared with mammalian class II RTKs, shows maximum 31% homology in the TK domain indicating that this the oldest member of class II RTK started to diverge from the common ancestral protein kinase approximately 650 million years ago. Using GCTK as a probe we identified three mRNA signals ranging from 2.6 to 0.6 kb. Kinase activity was localized only in the cell membranes from G. cydonium (M(r) = 65,000), and was not detected in the cytosol of this organism. Antibodies raised against a synthetic peptide, corresponding to the aa residues within the catalytic domain of the sponge TK, recognized strongly two proteins of M(r) = 65,000; these proteins, present in membrane fractions, also bound to the antiphosphotyrosine antibody. These data suggest that the TK cloned from the sponge is a membrane-associated 65 kDa protein. Moreover these results demonstrate that RTKs are present from the lowest group of multicellular eukaryotes, sponges, to mammals, and may suggest that RTKs are involved in a signal transduction pathway.}, } @article {pmid8106569, year = {1994}, author = {Freeman, MR and Bagli, DJ and Lamb, CC and Guthrie, PD and Uchida, T and Slavin, RE and Chung, LW}, title = {Culture of a prostatic cell line in basement membrane gels results in an enhancement of malignant properties and constitutive alterations in gene expression.}, journal = {Journal of cellular physiology}, volume = {158}, number = {2}, pages = {325-336}, doi = {10.1002/jcp.1041580215}, pmid = {8106569}, issn = {0021-9541}, mesh = {Animals ; Basement Membrane/physiology ; Cell Line ; Cell Line, Transformed ; Cytological Techniques ; Dogs ; Extracellular Matrix/physiology ; Gels ; *Gene Expression ; Male ; Prostate/*cytology/*physiology ; Prostatic Neoplasms/*etiology ; Rats ; Time Factors ; Tumor Cells, Cultured ; }, abstract = {Interaction of a transformed rat prostate epithelial cell (NbMC-2) with basement membrane gels (Matrigel) has been evaluated using a long-term matrix culture system. NbMC-2 cells, and single-cell clonal derivatives, formed spheroidal multicellular structures (aggregates) on Matrigel surfaces and were weakly invasive or noninvasive during a 1 week period. During subsequent 2-4 week periods, invasive cells originating from the aggregates and exhibiting a fusiform morphology became evident and increased in number in the matrix cultures. This biphasic pattern of behavior did not occur on laminin, type I or type IV collagen, or fibronectin substrates, but it did occur on Matrigel in serum-free medium. Characterization of sublines enriched in fusiform cells indicated that they maintained their distinct morphology with continuous culture. Further, they exhibited significantly greater invasive potential, saturation density, and random motility (chemokinesis) than the parent cell line. Steady-state levels of fibronectin mRNA were highly elevated in the fusiform variants, demonstrating a constitutive alteration in patterns of gene expression coinciding with the altered morphology. These results indicate that clonal NbMC-2 cells differentiate at a reproducible frequency into a more aggressive cell type in response to culture in the basement membrane-like matrix. The altered phenotypic properties appear to be stable since they can be inherited by daughter cells and because they are evident in the absence of matrix. These observations suggest a cell-specific mechanism for promotion of malignant growth by matrix-mediated induction of novel cell properties.}, } @article {pmid8121801, year = {1994}, author = {Thatcher, TH and Gorovsky, MA}, title = {Phylogenetic analysis of the core histones H2A, H2B, H3, and H4.}, journal = {Nucleic acids research}, volume = {22}, number = {2}, pages = {174-179}, pmid = {8121801}, issn = {0305-1048}, support = {GM-21793/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Conserved Sequence ; Fungi ; Histones/*genetics ; Humans ; Molecular Sequence Data ; Multigene Family ; *Phylogeny ; Plants ; }, abstract = {Despite the ubiquity of histones in eukaryotes and their important role in determining the structure and function of chromatin, no detailed studies of the evolution of the histones have been reported. We have constructed phylogenetic trees for the core histones H2A, H2B, H3, and H4. Histones which form dimers (H2A/H2B and H3/H4) have very similar trees and appear to have co-evolved, with the exception of the divergent sea urchin testis H2Bs, for which no corresponding divergent H2As have been identified. The trees for H2A and H2B also support the theory that animals and fungi have a common ancestor. H3 and H4 are 10-fold less divergent than H2A and H2B. Three evolutionary histories are observed for histone variants. H2A.F/Z-type variants arose once early in evolution, while H2A.X variants arose separately, during the evolution of multicellular animals. H3.3-type variants have arisen in multiple independent events.}, } @article {pmid8126058, year = {1994}, author = {Kohno, N and Ohnuma, T and Truog, P}, title = {Effects of hyaluronidase on doxorubicin penetration into squamous carcinoma multicellular tumor spheroids and its cell lethality.}, journal = {Journal of cancer research and clinical oncology}, volume = {120}, number = {5}, pages = {293-297}, pmid = {8126058}, issn = {0171-5216}, mesh = {Carcinoma, Squamous Cell/*drug therapy/*metabolism ; Cell Death/drug effects ; Doxorubicin/*pharmacokinetics/*toxicity ; Drug Interactions ; Humans ; Hyaluronic Acid/analysis ; Hyaluronoglucosaminidase/*pharmacology ; Kinetics ; Laryngeal Neoplasms/*drug therapy/*metabolism ; Lung Neoplasms/*drug therapy/*metabolism ; Tumor Cells, Cultured ; }, abstract = {Doxorubicin is an anticancer agent widely used in the treatment of human cancer. The major limitation of this drug governing the cell-killing effect appears to be its poor penetration into a tumor mass. We have studied the effects of hyaluronidase on the penetration and cell-killing effect of doxorubicin using multicellular tumor spheroids (MTS). MTS approximately 500 microns in diameter were produced by a liquid-overlay culture technique from PC-10 lung and HEp-2 laryngeal squamous carcinoma cell lines. Cells in MTS and monolayer were exposed to hyaluronidase for various lengths of time; this was followed by a 1-h resting interval and a subsequent 1-h exposure to doxorubicin. MTS and monolayer cells were then trypsinized to a single-cell suspension and subjected to clonogenic assay. Hyaluronidase at a concentration of 25 U/ml or 250 U/ml was nontoxic to the monolayer cells. For PC-10 MTS, pretreatment with 25 U/ml hyaluronidase for 24 h and 72 h resulted in approximately 20% increases in Doxorubicin cell killing at the median (IC50) dose as compared to doxorubicin alone. HEp-2 MTS were more sensitive to the hyaluronidase pretreatment. Thus, a 1-h exposure to the enzyme produced a 40% increase in doxorubicin-induced cell death at the IC50 dose. A fluorescence microscopic study revealed that a 1-h exposure of MTS to doxorubicin produced doxorubicin fluorescence only in the one or two outer layers of MTS. When MTS were pretreated with hyaluronidase, there was enhanced penetration of doxorubicin fluorescence into the MTS core. Hyaluronidase-induced enhancement of Doxorubicin penetration and its cell-killing effect is dependent on the exposure time and tumor cell origin. These data suggest that anecdotal reports of hyaluronidase-enhanced activity of preclinical chemotherapy deserve a controlled trial.}, } @article {pmid8079730, year = {1994}, author = {Kunz, LA and Groebe, K and Mueller-Klieser, W}, title = {Oncogene-associated growth behavior and oxygenation of multicellular spheroids from rat embryo fibroblasts.}, journal = {Advances in experimental medicine and biology}, volume = {345}, number = {}, pages = {359-366}, doi = {10.1007/978-1-4615-2468-7_47}, pmid = {8079730}, issn = {0065-2598}, mesh = {Animals ; Cell Division/genetics ; Cell Line ; Cell Transformation, Neoplastic/*genetics/metabolism/pathology ; Cocarcinogenesis ; Embryo, Mammalian ; Fibroblasts/cytology/metabolism ; Genes, myc ; Genes, ras ; *Oncogenes ; Oxygen Consumption/genetics ; Rats ; }, abstract = {The basis of the present investigation was the establishment of an oncogene-dependent, genetically determined two-stage carcinogenesis in vitro model as multicellular spheroids. Spheroid formation was achieved with four rat embryo fibroblast cell lines, two of which represent the first step of malignant transformation, known as stage of immortalization. The ras-transfected counterparts of these two parental cell clones represent fully transformed phenotypes. The data obtained show that spheroid volume growth and cellular viability reflect the degree of tumorigenicity in vivo of the different fibroblast types investigated. In addition, ras-transfection alters not only the growth kinetics but also the cellular oxygen metabolism. Furthermore, the results demonstrate very clearly that different fibroblast clones at the same stage of malignant transformation may be characterized by an entirely different growth behavior, morphology and metabolic activity in spheroid culture. This is true, although these cells originate from the same primary cells, differ only in the step of immortalization, and were cultured as spheroids under identical environmental conditions.}, } @article {pmid7579526, year = {1994}, author = {Wolpert, L}, title = {The evolutionary origin of development: cycles, patterning, privilege and continuity.}, journal = {Development (Cambridge, England). Supplement}, volume = {}, number = {}, pages = {79-84}, pmid = {7579526}, mesh = {Animals ; *Biological Evolution ; Cell Cycle ; Cell Differentiation ; Cell Division ; *Embryo, Nonmammalian ; Germ Layers/cytology ; Morphogenesis ; }, abstract = {A scenario for the evolution of a simple spherical multicellular organism from a single eukaryotic cell is proposed. Its evolution is based on environmentally induced alterations in the cell cycle, which then, by the Baldwin effect, become autonomous. Further patterning of this primitive organism--a Blastaea, could again involve environmentally induced signals like contact with the substratum, which could then become autonomous, by, perhaps, cytoplasmic localization and asymmetric cell division. Generating differences between cells based on positional information is probably very primitive, and is well conserved; its relation to asymmetric cell division is still unclear. Differentiation of new cell types can arise from non equivalence and gene duplication. Periodicity also evolved very early on. The origin of gastrulation may be related to mechanisms of feeding. The embryo may be evolutionarily privileged and this may facilitate the evolution of novel forms. Larvae are secondarily derived and direct development is the primitive condition as required by the continuity principle.}, } @article {pmid7579522, year = {1994}, author = {Chothia, C}, title = {Protein families in the metazoan genome.}, journal = {Development (Cambridge, England). Supplement}, volume = {}, number = {}, pages = {27-33}, pmid = {7579522}, mesh = {Animals ; *Evolution, Molecular ; Exons ; Introns ; Invertebrates/*genetics ; Molecular Structure ; Multigene Family ; Mutation ; Protein Conformation ; Proteins/*genetics ; }, abstract = {The evolution of development involves the development of new proteins. Estimates based on the initial results of the genome projects, and on the data banks of protein sequences and structures, suggest that the large majority of proteins come from no more than one thousand families. Members of a family are descended from a common ancestor. Protein families evolve by gene duplication and mutation. Mutations change the conformation of the peripheral regions of proteins; i.e. the regions that are involved, at least in part, in their function. If mutations proceed until only 20% of the residues in related proteins are identical, it is common for the conformational changes to affect half the structure. Most of the proteins involved in the interactions of cells, and in their assembly to form multicellular organisms, are mosaic proteins. These are large and have a modular structure, in that they are built of sets of homologous domains that are drawn from a relatively small number of protein families. Patthy's model for the evolution of mosaic proteins describes how they arose through the insertion of introns into genes, gene duplications and intronic recombination. The rates of progress in the genome sequencing projects, and in protein structure analyses, means that in a few years we will have a fairly complete outline description of the molecules responsible for the structure and function of organisms at several different levels of developmental complexity. This should make a major contribution to our understanding of the evolution of development.}, } @article {pmid8149813, year = {1993}, author = {Imsiecke, G and Pascheberg, U and Müller, WE}, title = {Preparation and karyotype analysis of mitotic chromosomes of the freshwater sponge Spongilla lacustris.}, journal = {Chromosoma}, volume = {102}, number = {10}, pages = {724-727}, pmid = {8149813}, issn = {0009-5915}, mesh = {Animals ; DNA/*analysis ; Karyotyping ; Microscopy, Electron ; Mitosis/*genetics ; Porifera/*genetics ; }, abstract = {The present study documents for the first time the karyotype and mitotic chromosomes of a sponge. For the studies the freshwater sponge Spongilla lacustris (Lin. 1758) was used. Its karyotype comprises nine different chromosome pairs ranging in size from 2.1 to < or = 0.7 microns. Changes in size and shape of the chromosomes during the progression of mitosis are documented both light and electron microscopically. The data reveal that the lowest multicellular eukaryotes, the sponges, have already reached a high level of evolution of the mitotic mechanism.}, } @article {pmid7906442, year = {1993}, author = {Shenk, MA and Steele, RE}, title = {A molecular snapshot of the metazoan 'Eve'.}, journal = {Trends in biochemical sciences}, volume = {18}, number = {12}, pages = {459-463}, doi = {10.1016/0968-0004(93)90003-6}, pmid = {7906442}, issn = {0968-0004}, mesh = {Animals ; Cell Communication/genetics/physiology ; Cnidaria/*genetics ; Drosophila ; Extracellular Matrix Proteins/genetics/physiology ; Molecular Biology ; *Phylogeny ; Signal Transduction/genetics/physiology ; Transcription Factors/genetics/physiology ; }, abstract = {A description of the molecular make-up of the ancestral multicellular animal is emerging from the growing availability of molecular biological and biochemical data gleaned from the study of modern members of ancient groups of animals. We use the distributions of classes of transcription factors, signal transduction systems and other molecular innovations among metazoan phyla to infer some of the characteristics of the first animals.}, } @article {pmid8246452, year = {1993}, author = {Medlock, ES and McKenna, SD and Goldschneider, I}, title = {A selective culture system for generating terminal deoxynucleotidyl transferase-positive lymphoid cells in vitro. III. Structure of the bone marrow microenvironment for early lymphopoiesis.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {69}, number = {5}, pages = {616-628}, pmid = {8246452}, issn = {0023-6837}, support = {AI-32752/AI/NIAID NIH HHS/United States ; GM-38306/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bone Marrow/chemistry/*enzymology ; *Bone Marrow Cells ; Cell Differentiation/physiology ; Cells, Cultured ; DNA Nucleotidylexotransferase/*analysis ; Hematopoiesis/*physiology ; Methods ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Rats ; Rats, Inbred Lew ; Stem Cells/chemistry/*cytology/*enzymology ; Time Factors ; }, abstract = {BACKGROUND: We have previously demonstrated the feasibility of generating terminal deoxynucleotidyl transferase-positive (TdT+) lymphoid precursor cells in vitro in the nonadherent compartment of a long-term xenogeneic culture system in which rat bone marrow (BM) cells are seeded onto established mouse BM adherent cell layers. We have also noted that the appearance of TdT+ cells in these cultures is preceded by the formation of clusters of lymphoblasts in close association with the mouse BM adherent cell layer. Inasmuch as the selective generation of such primitive lymphoid cells is not ordinarily observed in homogeneic (i.e., mouse: mouse, rat:rat) BM cultures, the nature of the microenvironment for the generation of committed lymphoid stem/progenitor cells has not yet been detailed. Consequently, the aim of this study was to define the cellular components in the adherent compartment of our xenogeneic culture system that are associated with the earliest stages of lymphopoiesis in vitro.

EXPERIMENTAL DESIGN: The nature of the interactions between rat BM lymphoid precursor cells and mouse BM adherent microenvironmental cells was investigated by a combination of immunophenotyping and scanning and transmission electron microscopy of primary cultures. The kinetics of formation and composition of lymphoid clusters were also determined morphologically and phenotypically. Results were compared with those of other investigators who have studied lymphopoiesis in intact BM or in homogeneic cultures of pre-B cells.

RESULTS: Two distinct microenvironmental regions are represented within the mouse BM adherent cell layer: (a) paucilayer (PL) regions, composed of two or three horizontally oriented layers of alkaline phosphatase-positive mouse stromal cells; and (b) multilayer (ML) regions, containing 4 to 8 layers of such stromal cells. In both regions, proliferating rat lymphoid cells, expressing the HIS24 (B220) and/or HIS50 (heat stable antigen) early B-lineage antigens, are "sandwiched" between adjacent layers of stromal cells and enveloped by cytoplasmic processes from interdigitating mouse macrophages (pseudoemperipolesis). More than 95% of the lymphoid cells are of rat origin, whereas more than 95% of the nonlymphoid cells are of mouse origin. Large clusters, containing up to 1,000 lymphoid cells, preferentially develop in the ML regions and are comprised primarily of TdT+ cells. Small clusters containing 5 to 50 lymphoid cells, preferentially develop in the PL regions and are comprised primarily of TdT- cells, that can generate TdT+ cells upon transfer onto fresh adherent cells layers. Formation of individual small clusters, which outnumber large clusters by approximately 10-fold, is initiated by as few as 25 unfractionated rat BM cells. This process is not preceded by a lag period, and is linear with respect to time and cell dose. Formation of large clusters requires approximately 30 times more input cells, and is linear with respect to time after a lag of 5 days.

CONCLUSIONS: The number of small lymphoid clusters formed in vitro closely approximates the frequency of lymphoid stem/progenitor cells in the BM inoculum (3 to 5%). This suggests that, under ideal conditions, individual clusters are clonally derived and the seeding efficiency of the culture system approaches 100%. The results further suggest that large clusters are formed by the coalescence of numerous small clusters within ML regions of the adherent cell layer; and that the formation of ML regions may be supported by an underlying monolayer of macrophages. A novel aspect of this system appears to be the frequency of pseudoemperipolesis, rather than phagocytosis, of primitive lymphoid cells by macrophages, that has also been noted in vivo. Moreover, the ML regions themselves bear a close resemblance to the recently described pro-B cell-enriched, multicellular aggregate fraction of freshly harvested mouse BM. Hence, this system appears to structurally recreate in vitro the}, } @article {pmid8243991, year = {1993}, author = {Kaiser, D}, title = {Roland Thaxter's legacy and the origins of multicellular development.}, journal = {Genetics}, volume = {135}, number = {2}, pages = {249-254}, doi = {10.1093/genetics/135.2.249}, pmid = {8243991}, issn = {0016-6731}, mesh = {Animals ; Ascomycota/*growth & development ; Developmental Biology/history ; Dictyostelium/genetics/*growth & development ; History, 19th Century ; Morphogenesis ; Myxococcales/genetics/*growth & development ; Phylogeny ; }, } @article {pmid8219058, year = {1993}, author = {Valentin, K and Kostrzewa, M and Zetsche, K}, title = {Glutamate synthase is plastid-encoded in a red alga: implications for the evolution of glutamate synthases.}, journal = {Plant molecular biology}, volume = {23}, number = {1}, pages = {77-85}, pmid = {8219058}, issn = {0167-4412}, mesh = {Amino Acid Sequence ; *Biological Evolution ; Blotting, Northern ; Blotting, Southern ; Cloning, Molecular ; Glutamate Synthase/*genetics/metabolism ; Molecular Sequence Data ; Plastids/*enzymology ; Rhodophyta/enzymology/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {An actively transcribed gene (glsF) encoding for ferredoxin-dependent glutamate synthase (Fd-GOGAT) was found on the plastid genome of the multicellular red alga Antithamnion sp. Fd-GOGAT is not plastid-encoded in chlorophytic plants, demonstrating that red algal plastid genomes encode for additional functions when compared to those known from green chloroplasts. Moreover, our results suggest that the plant Fd-GOGAT has an endosymbiotic origin. The same may not be true for NADPH-dependent GOGAT. In Antithamnion glsF is flanked upstream by cpcBA and downstream by psaC and is transcribed monocistronically. Implications of these results for the evolution of GOGAT enzymes and the plastid genome are discussed.}, } @article {pmid8219057, year = {1993}, author = {Kostrzewa, M and Zetsche, K}, title = {Organization of plastid-encoded ATPase genes and flanking regions including homologues of infB and tsf in the thermophilic red alga Galdieria sulphuraria.}, journal = {Plant molecular biology}, volume = {23}, number = {1}, pages = {67-76}, pmid = {8219057}, issn = {0167-4412}, mesh = {Adenosine Triphosphatases/*genetics ; Amino Acid Sequence ; Biological Evolution ; Blotting, Northern ; Molecular Sequence Data ; Phylogeny ; Plastids/*enzymology ; Restriction Mapping ; Rhodophyta/enzymology/*genetics ; Sequence Homology, Amino Acid ; Transcription, Genetic ; }, abstract = {We have cloned and sequenced the plastid ATPase operons (atp1 and atp2) and flanking regions from the unicellular red alga Galdieria sulphuraria (Cyanidium caldarium). Six genes (5 atpI, H, G, F, D and A 3) are linked in atp1 encoding ATPase subunits a, c, b, b, delta and alpha, respectively. The atpF gene does not contain an intron and overlaps atpD by 1 bp. As in the genome of chloroplasts from land plants, the cluster is located downstream of rps2, but between this gene and atp1 we found the gene for the prokaryotic translation elongation factor TS. Downstream of atpA, we detected two open reading frames, one encoding a putative transport protein. The genes atpB and atpE, encoding ATPase subunits beta and epsilon, respectively, are linked in atp2, separated by a 2 bp spacer. Upstream of atpB, an uninterrupted orf167 was detected which is homologous to an intron-containing open reading frame in land plant chloroplasts. This orf167 is preceded on the opposite DNA strand by a homologue to initiation factor 2 in prokaryotes. The arrangement of atp1 and atp2 is the same as observed in the multicellular red alga Antithamnion sp., indicating a conserved genome arrangement in the red algal plastid genome. Differences compared to green chloroplast genomes suggest a large phylogenetic distance between red algae and green plants, while similarities in arrangement and sequence to chromophytic ATPase operons support a red algal origin of chlorophyll a/c-containing plastids or alternatively point to a common prokaryotic endosymbiont.}, } @article {pmid8117577, year = {1993}, author = {Gooden, BA}, title = {The evolution of asphyxial defense.}, journal = {Integrative physiological and behavioral science : the official journal of the Pavlovian Society}, volume = {28}, number = {4}, pages = {317-330}, pmid = {8117577}, issn = {1053-881X}, mesh = {Animals ; Asphyxia/*physiopathology ; Biological Evolution ; Humans ; }, abstract = {From the time animals became dependent upon molecular oxygen as an integral part of their energy-producing processes, they have remained in the shadow of acute asphyxial threat--the blocking of respiratory exchange resulting in the intracellular triad of hypoxia, hypercapnia and acidosis. The most commonly occurring precipitant of acute asphyxia has always been the transfer between air and water environments. Over the last one hundred years studies on a wide range of living organisms, from single cells to complex multicellular organisms like mammals, have demonstrated the presence of well-defined metabolic and cardiovascular-respiratory mechanisms for protecting living things against acute asphyxia. Single-celled animals depend upon anaerobiosis and secondarily hypometabolism. In addition to these processes, animals with gills or lungs utilize "passive" protection such as increased oxygen storage and the "dynamic" cardiovascular adjustments of bradycardia and selective ischemia. These latter changes decrease overall oxygen consumption and hence utilize the oxygen stores in the most economical way to protect the cardiac and cerebral tissue, which are most sensitive to hypoxia and vital to continued survival of the organism. In this article an attempt is made to place these processes into an evolutionary context. As through a glass darkly we glimpse asphyxial defense running like a paleophysiological thread through hundreds of millions of years, being accentuated here and muted there, depending upon the particular needs of individual species.}, } @article {pmid8234363, year = {1993}, author = {Parker, GA}, title = {Sperm competition games: sperm size and sperm number under adult control.}, journal = {Proceedings. Biological sciences}, volume = {253}, number = {1338}, pages = {245-254}, doi = {10.1098/rspb.1993.0110}, pmid = {8234363}, issn = {0962-8452}, mesh = {Animals ; *Biological Evolution ; Ejaculation ; Female ; Fertilization ; Male ; Mathematics ; *Models, Biological ; Sperm Count ; Spermatozoa/cytology/*physiology ; }, abstract = {Evolutionary games of sperm competition in which two males mate with the same female have previously considered sperm size to be fixed at some (small) constant level. Although male gametes in multicellular organisms are typically small compared with ova, they vary greatly both between and within groups, and sperm size sometimes correlates with the probability of sperm competition. This paper examines 'raffle principle' sperm competition games in which both size and number of gametes can be varied strategically under control of the diploid parent. If ejaculate investment trades off against the number of matings that a male can achieve, the evolutionary stable strategy (ESS) ejaculate expenditure (as a fraction of reproductive effort per mating) approximates to p/4 when the probability, p, of sperm competition is low. Sperm size may either: (i) increase a sperm's competitive weight (a measure of its advantage in the fertilization raffle), or (ii) influence its mortality rate in the female tract. On the simplest model, size is optimized after the marginal value theorem, and may be large or small depending on how size influences competitive weight or survivorship. Further, sperm size is independent of the risk of sperm competition, and only sperm numbers increase with this risk. However, some recent studies show sperm size to increase with sperm competition. The present analysis offers the following possibilities: (i) there are unidentified constraints on sperm number, so that ejaculate mass can increase only by increase in sperm size; (ii) competitive benefits of size become more important as sperm numbers increase; (iii) size mainly increases survivorship, and sperm competition risk increases with the mean duration between mating and fertilization; and (iv) size increases competitive ability at the expense of survivorship, and sperm competition risk decreases with time between mating and fertilization. These conclusions relate to advantages conferred by size on sperm before fertilization; they do not affect the prediction of previous models that no component of sperm size should evolve for provisioning the zygote.}, } @article {pmid8401474, year = {1993}, author = {Hinkle, G and Sogin, ML}, title = {The evolution of the Vahlkampfiidae as deduced from 16S-like ribosomal RNA analysis.}, journal = {The Journal of eukaryotic microbiology}, volume = {40}, number = {5}, pages = {599-603}, doi = {10.1111/j.1550-7408.1993.tb06114.x}, pmid = {8401474}, issn = {1066-5234}, support = {GM32964/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; *Biological Evolution ; Molecular Sequence Data ; Phylogeny ; RNA, Protozoan/*genetics ; RNA, Ribosomal, 16S/*genetics ; Schizopyrenida/classification/*genetics ; }, abstract = {The amoebae, a phenotypically diverse, paraphyletic group of protists, have been largely neglected by molecular phylogeneticists. To better understand the evolution of amoebae, we sequenced and analyzed the 16S-like ribosomal RNA genes of three vahlkampfiid amoebae: Paratetramitus jugosus, Tetramitus rostratus and Vahlkampfia lobospinosa. The Vahlkampfiidae lineage is monophyletic, branches early along the eukaryotic line of descent, and is not a close relative of the multicellular amoebae that also reversibly transform from amoebae to flagellates.}, } @article {pmid8256088, year = {1993}, author = {Chavasse, DC and Post, RJ and Davies, JB and Whitworth, JA}, title = {Absence of sperm from the seminal receptacle of female Onchocerca volvulus following multiple doses of ivermectin.}, journal = {Tropical medicine and parasitology : official organ of Deutsche Tropenmedizinische Gesellschaft and of Deutsche Gesellschaft fur Technische Zusammenarbeit (GTZ)}, volume = {44}, number = {3}, pages = {155-158}, pmid = {8256088}, issn = {0177-2392}, mesh = {Animals ; Dose-Response Relationship, Drug ; Double-Blind Method ; Female ; Fertilization/drug effects ; Humans ; Insemination/drug effects ; Ivermectin/*pharmacology/therapeutic use ; Male ; Onchocerca volvulus/*drug effects/physiology ; Onchocerciasis/drug therapy/*parasitology ; Oogenesis/drug effects ; Spermatozoa/drug effects ; }, abstract = {It is already known that multiple doses of ivermectin have a profound effect on embryonic development in Onchocerca volvulus and that this appears to operate mainly at the single cell stage. To investigate this further, we examined adult female O. volvulus originating from patients treated either with placebo or one, four or five doses of ivermectin. The reproductive organs were dissected out of the worm and examined for evidence of oogenesis and for the quantity of sperm and oocytes in the seminal receptacles. A single dose of ivermectin had no measurable effect on oogenesis or on the amount of sperm and oocytes compared to placebo. However after multiple doses of ivermectin a significantly lower proportion of seminal receptacles contained sperm and there was a significantly higher proportion of ovaries with impaired oogenesis compared to placebo. It is concluded that the reduction in the number of multicellular embryonic stages from worms exposed to multiple doses of ivermectin is due, at least in part, to a major reduction in the effective insemination of female worms and to a minor impairment of oogenesis.}, } @article {pmid8411203, year = {1993}, author = {Sueoka, N}, title = {Directional mutation pressure, mutator mutations, and dynamics of molecular evolution.}, journal = {Journal of molecular evolution}, volume = {37}, number = {2}, pages = {137-153}, pmid = {8411203}, issn = {0022-2844}, mesh = {Animals ; Base Composition ; *Biological Evolution ; Codon/genetics ; DNA/chemistry/genetics ; Genetics, Population ; Models, Genetic ; *Mutation ; Phylogeny ; Sequence Homology, Nucleic Acid ; }, abstract = {Using a general form of the directional mutation theory, this paper analyzes the effect of mutations in mutator genes on the G+C content of DNA, the frequency of substitution mutations, and evolutionary changes (cumulative mutations) under various degrees of selective constraints. Directional mutation theory predicts that when the mutational bias between A/T and G/C nucleotide pairs is equilibrated with the base composition of a neutral set of DNA nucleotides, the mutation frequency per gene will be much lower than the frequency immediately after the mutator mutation takes place. This prediction explains the wide variation of the DNA G+C content among unicellular organisms and possibly also the wide intragenomic heterogeneity of third codon positions for the genes of multicellular eukaryotes. The present analyses lead to several predictions that are not consistent with a number of the frequently held assumptions in the field of molecular evolution, including belief in a constant rate of evolution, symmetric branching of phylogenetic trees, the generality of higher mutation frequency for neutral sets of nucleotides, the notion that mutator mutations are generally deleterious because of their high mutation rates, and teleological explanations of DNA base composition.}, } @article {pmid8400545, year = {1993}, author = {Hirabayashi, J and Kasai, K}, title = {The family of metazoan metal-independent beta-galactoside-binding lectins: structure, function and molecular evolution.}, journal = {Glycobiology}, volume = {3}, number = {4}, pages = {297-304}, doi = {10.1093/glycob/3.4.297}, pmid = {8400545}, issn = {0959-6658}, mesh = {Amino Acid Sequence ; Animals ; Biological Evolution ; Galactosides/*metabolism ; Galectins ; Hemagglutinins/*classification/genetics/metabolism ; Invertebrates/*chemistry/genetics ; Membrane Glycoproteins/*classification/genetics/metabolism ; Metals/metabolism ; Molecular Sequence Data ; }, abstract = {Animal metal-independent beta-galactoside-binding lectins were initially found in vertebrates, but they have recently been isolated from much lower invertebrates, such as nematode and sponge, as well. Further, an eosinophilic lysophospholipase associated with various inflammatory reactions was very recently found to be a new member of this protein family. It appears that beta-galactoside-binding lectins and some non-lectin proteins form a superfamily whose members are widely distributed from vertebrates to invertebrates. From the viewpoints of protein architecture, the superfamily members can be subdivided into three types; i.e. 'proto type' (the relatively well-studied 14 kDa lectins), 'chimera type' (29-35 kDa lectins also known as epsilon BP/CBP35/Mac2/laminin-binding protein) and 'tandem-repeat type' (a newly found nematode 32 kDa lectin). Comparison of their amino acid sequences and mutagenesis studies have suggested the functional importance of some conservative hydrophilic residues (His44, Asn46, Arg48, Glu71 and Arg73 of human 14 kDa lectin). Several non-charged residues (Gly14, Phe45, Pro47, Phe49, Val59, Trp68, Pro78 and Phe79) are also well conserved, and are probably important to maintain the structural framework of these proteins. A consideration of molecular evolution suggests that lectins belonging to this family probably existed in the Precambrian era. Ubiquitous occurrence of these homologous lectins with shared sugar specificity suggests that they are involved in 'essential minimum' functions of multicellular animals, possibly in cooperation with their partner glycoconjugates.}, } @article {pmid8350596, year = {1993}, author = {Michaelson, J}, title = {Cellular selection in the genesis of multicellular organization.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {69}, number = {2}, pages = {136-151}, pmid = {8350596}, issn = {0023-6837}, support = {CA37374/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Cell Division ; *Cell Physiological Phenomena ; Embryo, Mammalian/cytology ; Embryonic and Fetal Development ; Gene Expression ; Humans ; Immune System/physiology ; *Selection, Genetic ; Stochastic Processes ; }, } @article {pmid8297931, year = {1993}, author = {Finch, CE}, title = {FRAR course on laboratory approaches to aging. Theories of aging.}, journal = {Aging (Milan, Italy)}, volume = {5}, number = {4}, pages = {277-289}, pmid = {8297931}, issn = {0394-9532}, mesh = {*Aging/genetics/physiology ; Animals ; Biological Evolution ; Diet ; Ecosystem ; Female ; Gene Expression ; Humans ; Male ; *Models, Biological ; Neurosecretory Systems/physiology ; Reproduction ; }, abstract = {This review of gerontological theory cites diverse examples of neural and endocrine involvement in the senescence of mammals and some other multicellular species that suggest fundamental involvement in age-related changes in cell functions. The data support the major hypothesis that age-related changes are generally caused by specific physiological factors that are extrinsic to cells. The success of these manipulations includes retarding or reversing specific age-related changes, and extending the life span. From another perspective, these findings have converted time in the analysis of senescence from an independent variable to a dependent variable. So far, we do not need to hypothesize any new mechanism that is not already known in disease or normal functioning.}, } @article {pmid8346026, year = {1993}, author = {Degnan, BM and Degnan, SM and Naganuma, T and Morse, DE}, title = {The ets multigene family is conserved throughout the Metazoa.}, journal = {Nucleic acids research}, volume = {21}, number = {15}, pages = {3479-3484}, pmid = {8346026}, issn = {0305-1048}, support = {R01-CA53105/CA/NCI NIH HHS/United States ; R01-RR06640/RR/NCRR NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Annelida/genetics ; Binding Sites ; *Biological Evolution ; Chordata, Nonvertebrate/genetics ; *Conserved Sequence ; Crustacea/genetics ; DNA/metabolism ; Echinodermata/genetics ; Invertebrates/*genetics ; Molecular Sequence Data ; Mollusca/genetics ; *Multigene Family ; Nematoda/genetics ; Polymerase Chain Reaction ; Porifera/genetics ; Proto-Oncogene Proteins/chemistry/*genetics ; Proto-Oncogene Proteins c-ets ; *Transcription Factors ; }, abstract = {This study provides the first empirical evidence for the conservation of the ets proto-oncogene transcription factor family throughout the Metazoa. Using the polymerase chain reaction with degenerate primers corresponding to conserved sequences within the ETS DNA-binding domain, we have detected ets genes in a range of lower metazoans, including sponges, ctenophores, anemones, flatworms and nematodes, and in several higher invertebrate metazoans. Many of these sequences are significantly divergent from the original v-ets-1 oncogene, although most can be aligned with recently defined groups within the ets gene family. Multiple ETS domain sequences were detected in a number of the lower metazoan species, providing evidence for the existence of an ets multigene family at the earliest stages of metazoan evolution. In contrast, we were unable to detect any ETS sequences in fungal, plant or several protozoan DNAs. Our findings suggest that the duplication and divergence of ets proto-oncogenes responsible for generating the multigene family occurred concomitantly with the development of metazoan animals. In addition, these data corroborate other recent molecular evidence in providing strong support for the monophyletic origin of all multicellular animals, including sponges.}, } @article {pmid8504930, year = {1993}, author = {Liang, C and Spitzer, JD and Smith, HS and Gerbi, SA}, title = {Replication initiates at a confined region during DNA amplification in Sciara DNA puff II/9A.}, journal = {Genes & development}, volume = {7}, number = {6}, pages = {1072-1084}, doi = {10.1101/gad.7.6.1072}, pmid = {8504930}, issn = {0890-9369}, support = {GM 35929/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Chromosome Mapping ; Cloning, Molecular ; DNA/*physiology ; *DNA Replication ; Diptera/embryology/*genetics ; Electrophoresis, Gel, Two-Dimensional ; Female ; *Gene Amplification ; Larva/genetics/growth & development ; Multigene Family ; Restriction Mapping ; }, abstract = {Two independent two-dimensional (2D) gel methods were used to map an origin of replication that is developmentally regulated by the steroid hormone ecdysone, namely an origin for DNA puff amplification in the fungus fly Sciara coprophila. Initiation of replication was found to occur within a small region of no larger than 6 kb by use of the neutral/neutral 2D gel method. Neutral/alkaline 2D gel analyses support the results of the neutral/neutral 2D gels and further define within the origin region an approximately 1-kb area where the majority of replication initiates. This is the first example of an origin of replication in multicellular eukaryotes that has been mapped by 2D gels to such a small defined region. Moreover, replication can be seen by the neutral/alkaline 2D gel method to proceed bidirectionally outward from this replication origin region. These data are consistent with an onion-skin mechanism whereby multiple rounds of DNA replication initiate at a specific origin of replication for Sciara DNA puff amplification.}, } @article {pmid8507494, year = {1993}, author = {Staiger, C and Doonan, J}, title = {Cell division in plants.}, journal = {Current opinion in cell biology}, volume = {5}, number = {2}, pages = {226-231}, doi = {10.1016/0955-0674(93)90107-2}, pmid = {8507494}, issn = {0955-0674}, mesh = {Cell Cycle/genetics ; Mitosis/*genetics ; *Plants/genetics ; Protein Kinases ; }, abstract = {The past couple of years have seen the isolation and characterization of many of the regulatory genes from plants that are thought to be intimately involved in regulation of the cell division cycle. In addition, characterization of plant-specific aspects of the cell division cycle has provided insight into how spatial and temporal controls may be linked. The comparative lack of cell mobility means that plant organs are historic records of the cell cycles that occurred during their evolution. Differentiated cells retain a capacity for re-entry into the cell cycle, which is probably an adaptation to compensate for the damage that they must tolerate because of a sedentary lifestyle. Understanding how plants cope with such damage and manage to generate such an array of diverse multicellular structures will require a basic comprehension of cell division.}, } @article {pmid8321157, year = {1993}, author = {Chigira, M}, title = {A general model of carcinogenesis (I)--Tumor evolution and gene deletion.}, journal = {Medical hypotheses}, volume = {40}, number = {4}, pages = {223-226}, doi = {10.1016/0306-9877(93)90045-r}, pmid = {8321157}, issn = {0306-9877}, mesh = {Animals ; DNA Repair ; *Gene Deletion ; Genes, Tumor Suppressor ; Humans ; *Models, Genetic ; Mutation ; Neoplasms/*genetics ; }, abstract = {Carcinogenesis is functionally a deletion alteration rather than addition of genetic information. Repressor genes may be more sensitive to 'neutral' mutations of DNA than those of structural genes, since selection pressure for deletion of repressors is extremely low in multicellular organisms. Dysfunction of repressors caused by genomic mutation induces autonomic expression of structural genes which is programmed a priori in each cell. Tumor progression can be explained by this deletion model with abnormal DNA repair. Alteration of DNA repairing units may be the initial mutation in carcinogenesis.}, } @article {pmid8383163, year = {1993}, author = {Maderna, P and Colli, S and Caruso, D and Eligini, S and Toia, A and Galli, G and Tremoli, E}, title = {Quantitative changes of hydroxyacid formation during platelet-neutrophil interaction.}, journal = {The Journal of laboratory and clinical medicine}, volume = {121}, number = {3}, pages = {406-414}, pmid = {8383163}, issn = {0022-2143}, mesh = {12-Hydroxy-5,8,10,14-eicosatetraenoic Acid ; Blood Platelets/*metabolism/physiology ; Cell Communication/*physiology ; Humans ; Hydroxyeicosatetraenoic Acids/*biosynthesis ; Leukotriene B4/*biosynthesis ; Neutrophils/*metabolism/physiology ; Thromboxane B2/*biosynthesis ; }, abstract = {In recent years the interactions between lipoxygenase enzymes present in platelets and leukocytes, resulting in the transcellular biosynthesis of eicosanoids, have been discovered and their relevance in thrombotic and inflammatory disorders recognized. However, attention has focused on the synthesis of novel products, not normally formed by the single-cell population. Less information is available on the changes in hydroxyacid formation during platelet-neutrophil interactions. In this study, we evaluated the quantitative changes of the levels of 12- and 5-hydroxyeicosatetraenoic acids, leukotriene B4, and thromboxane B2 occurring during the incubation of platelet-neutrophil mixed suspensions stimulated with the calcium ionophore A23187. Cell-to-cell interaction resulted in quantitative changes of the level of hydroxyacids; in mixed platelet-neutrophil suspensions, the levels of 12-hydroxyeicosatetraenoic acid were significantly increased with respect to those measured in platelets incubated alone. The amount of 5-hydroxyeicosatetraenoic acid formed by neutrophils was significantly decreased by the presence of platelets in the incubation medium. In addition, a slight but significant reduction in leukotriene B4 synthesis was observed. Concomitantly with these changes, the formation of thromboxane B2 by platelets was modified, indicating that--besides the lipoxygenase pathway--the arachidonic acid metabolism by cyclooxygenase is affected. Our study demonstrates that in mixed platelet-neutrophil suspensions profound quantitative modifications in hydroxyacid and thromboxane synthesis occur, indicating that the overall balance of arachidonic acid products may be altered in pathologic conditions in which early events of multicellular origin have been recognized.}, } @article {pmid8364691, year = {1993}, author = {West, L and Powers, D}, title = {Molecular phylogenetic position of hexactinellid sponges in relation to the Protista and Demospongiae.}, journal = {Molecular marine biology and biotechnology}, volume = {2}, number = {2}, pages = {71-75}, pmid = {8364691}, issn = {1053-6426}, mesh = {Animals ; Base Sequence ; DNA, Ribosomal/chemistry/isolation & purification ; Eukaryota/*classification/genetics ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; Porifera/*classification/genetics ; RNA, Ribosomal, 18S/genetics ; }, abstract = {Although it is generally accepted that the first multicellular organisms arose from unicellular ancestors, the phylogenetic relationships linking these groups remain unclear. Anatomical, physiological, and molecular studies of current multicellular organisms with relatively simple body organization suggest key characteristics of the earliest multicellular lineages. Glass sponges, the Hexactinellida, possess cellular characteristics that resemble some unicellular protistan organisms. These unique sponges were abundant in shallow seas of the early Cambrian, but they are currently restricted to polar habitats or very deep regions of the world oceans. Due in part to their relative inaccessibility, their potential significance to the early phylogeny of the eukaryotic kingdoms has been largely overlooked. We used sequences of the 18s ribosomal RNA gene of Farrea occa, a representative of the deep-water hexactinellid sponges, and Coelocarteria singaporense, a representative of the more common demosponges, and compared them with selected ribosomal RNA gene sequences available within the Protista. Using four computational methods for phylogenetic analysis of ribosomal DNA sequences, we found that the hexactinellid sponge-demosponge cluster is most closely related to Volvox and Acanthamoeba.}, } @article {pmid8515679, year = {1993}, author = {Trosko, JE and Madhukar, BV and Chang, CC}, title = {Endogenous and exogenous modulation of gap junctional intercellular communication: toxicological and pharmacological implications.}, journal = {Life sciences}, volume = {53}, number = {1}, pages = {1-19}, doi = {10.1016/0024-3205(93)90606-4}, pmid = {8515679}, issn = {0024-3205}, support = {1P42ESO4911/ES/NIEHS NIH HHS/United States ; CA-21104/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Cell Communication/drug effects ; Homeostasis ; Humans ; Intercellular Junctions/*drug effects/*metabolism ; }, abstract = {During the evolution of single-celled organisms to multicellular metazoans, a family of highly conserved genes coding for proteins (connexins), which as hexameric units (connexins), has evolved to form intercellular channels (gap junctions). These gap junctions allow ions and small molecular weight molecules to flow between coupled cells, thereby facilitating synchronization of electrotonic or metabolic cooperation. Control of cell proliferation, cell differentiation and adaptive responses of differentiated cells have been speculated to be biological roles of gap junctions. The regulation of these gap junctions can occur at the transcriptional, translational and posttranslational levels. Transient downregulation by endogenous or exogenous chemicals can bring about adaptive or maladaptive consequences depending on circumstances. Stable abnormal regulation of gap junction function has been associated with the activation of several oncogenes. Several tumor suppressor genes have also been associated with the up-regulation of gap junction function. Since gap junctions exist in all organs of the multi-cellular organisms, the dysfunction of these gap junctions by various toxic chemicals which have cell type/tissue/organ specificity could bring about very distinct clinical consequences, such as embryo lethality or teratogenesis, reproductive dysfunction in the gonads, neurotoxicity of the CNS system, hyperplasia of the skin, and tumor promotion of initiated tissue. Understanding how many non-mutagenic chemicals might alter normal gap junction function should form the basis of "epigenetic" toxicology. On the other hand, restoring normal gap junction function to cells which have dysfunctional intercellular communication could be the basis for a new approach for therapeutic pharmaceuticals.}, } @article {pmid8437589, year = {1993}, author = {Levis, RW}, title = {Drosophila melanogaster does not share the telomeric repeat sequence of another invertebrate, Ascaris lumbricoides.}, journal = {Molecular & general genetics : MGG}, volume = {236}, number = {2-3}, pages = {440-442}, pmid = {8437589}, issn = {0026-8925}, support = {GM38259/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Ascaris lumbricoides/*genetics ; Biological Evolution ; DNA Probes ; Drosophila melanogaster/*genetics ; Nucleic Acid Hybridization ; Repetitive Sequences, Nucleic Acid/*genetics ; *Telomere ; }, abstract = {The DNA at the chromosomal termini of all eukaryotes from which it has been isolated contains a characteristic sequence motif consisting of tandem arrays of a regular or irregular repeat unit. These terminal repeats are thought to be essential for the maintenance of the chromosome ends. The sequences of the terminal repeats of all vertebrates studied thus far are identical and are similar enough to those of higher plants and some protozoans to cross-hybridize. However, previous studies have not detected cross-hybridization between the DNA of Drosophila melanogaster and the terminal DNA sequences of any of several organisms tested. Recently, the first terminal DNA clone from a multicellular invertebrate, that of Ascaris lumbricoides, was reported also to consist of a tandem reiteration of a short sequence similar to those previously identified for other eukaryotes. Here I show that a probe for this sequence from A. lumbricoides fails to hybridize detectably to the DNA of D. melanogaster. Thus, in contrast to their conservation among vertebrates, the terminal chromosomal sequences appear not to be shared by all metazoan invertebrates.}, } @article {pmid8374064, year = {1993}, author = {Desnitski, AG}, title = {On the origins and early evolution of multicellularity.}, journal = {Bio Systems}, volume = {29}, number = {2-3}, pages = {129-132}, doi = {10.1016/0303-2647(93)90088-t}, pmid = {8374064}, issn = {0303-2647}, mesh = {*Biological Evolution ; Cell Differentiation ; Chlorophyta/cytology/*genetics/growth & development ; Eukaryota/classification/cytology/genetics ; Models, Biological ; RNA, Ribosomal/genetics ; }, abstract = {In this paper an attempt is made to consider the significance of recent data on the organization and development of Volvox, a multicellular spheroidal green alga, for the unsolved problem of metazoan origins. A brief analysis is made of differences and similarities in some trends and principles during the establishment of metazoan and volvocalean multicellularity.}, } @article {pmid8019895, year = {1993}, author = {Garrone, R and Exposito, JY and Franc, JM and Franc, S and Humbert-David, N and Qin, L and Tillet, E}, title = {[Phylogenesis of the extracellular matrix].}, journal = {Comptes rendus des seances de la Societe de biologie et de ses filiales}, volume = {187}, number = {2}, pages = {114-123}, pmid = {8019895}, issn = {0037-9026}, mesh = {Animals ; Collagen/chemistry ; Extracellular Matrix/*chemistry ; Extracellular Matrix Proteins/chemistry ; Phylogeny ; Proteoglycans/chemistry ; }, abstract = {The extracellular matrix constitutes a highly organized intercellular medium. In multicellular animals, it plays important functions for cell cohesion and for the modulation of cell differentiation and behaviour as well. All the investigations conducted in non-vertebrate species have shown that the extracellular matrix is present at the onset of the multicellular life and throughout the animal kingdom. The collagen fibrils are the most constant element. Recent data on the structure of fibrillar collagen molecules and on the organization of the corresponding genes, obtained in sponges and sea-urchins have shown the remarkable conservation of these fibrillar collagens during evolution. This even emphasize their very likely fundamental function. These results, associated with data provided by morphological and biochemical informations obtained in cnidarians suggest that these primitive fibrillar collagens are the direct precursors of some vertebrate minor fibrillar collagens such as type V. Other collagens, with interrupted triple helix, are more variable and their characterization in sponges leads to consider these non-fibrillar collagens as precursors of basement membrane collagens, of fibril-associated collagens (the FACITs collagens), of the so-called "epithelial" collagens. They were probably used as sticking devices, anchoring the animal to its substratum, or as covering layers (cuticles, sheaths), and even as skeletons (i.e. the bath sponge). Adhesive molecules of higher animals ensure the mediation of the interactions between cells (via their membrane receptors of the integrin type) and the fibrous network of the extracellular matrix. It is the same situation at the beginning of the evolution of the multicellular animals where fibronectin, tenascin and then laminin are present. Proteoglycans too are components of primitive extracellular matrices. At last, only collagen mineralized by calcium phosphate (in bone) and elastin (in elastic fibers and laminae) seem to be restricted to vertebrates.}, } @article {pmid7956040, year = {1993}, author = {Bird, AP}, title = {Functions for DNA methylation in vertebrates.}, journal = {Cold Spring Harbor symposia on quantitative biology}, volume = {58}, number = {}, pages = {281-285}, doi = {10.1101/sqb.1993.058.01.033}, pmid = {7956040}, issn = {0091-7451}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {5-Methylcytosine ; Animals ; Binding Sites ; Biological Evolution ; Cytosine/analogs & derivatives/metabolism ; DNA/genetics/*metabolism ; Genes, Regulator ; Genome ; Methylation ; Transcription, Genetic ; Vertebrates ; }, abstract = {DNA methylation is ancestrally a mechanism for neutralizing potentially damaging DNA elements in the genome. The genomes of most multicellular organisms contain a small fraction of methylated DNA that contains the methylated elements, whereas the organism's own genes remain free of methylation. Vertebrates are exceptional among animals in that their genomes, including genes, are predominantly methylated. They retain the ability to inactivate viral DNA but have recruited the DNA methylation system for new functions. Widespread low-density methylation can contribute to lowering of the level of transcriptional "noise" from cryptic or inappropriate promoters. This may be the major advantage of DNA methylation in these organisms and may be sufficiently beneficial to offset the disadvantage of m5C mutability. The other novel feature of DNA methylation in vertebrates is the capacity to de novo methylate certain CpG islands, causing long-term strong repression. These evolutionary innovations may explain the high complexity of vertebrate organs and cell types.}, } @article {pmid1459436, year = {1992}, author = {Goldstein, DB}, title = {Heterozygote advantage and the evolution of a dominant diploid phase.}, journal = {Genetics}, volume = {132}, number = {4}, pages = {1195-1198}, pmid = {1459436}, issn = {0016-6731}, support = {GM 28016/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; *Diploidy ; Genes, Dominant ; Genetics, Population ; Haploidy ; *Heterozygote ; Ploidies ; *Selection, Genetic ; }, abstract = {The life cycle of eukaryotic, sexual species is divided into haploid and diploid phases. In multicellular animals and seed plants, the diploid phase is dominant, and the haploid phase is reduced to one, or a very few cells, which are dependent on the diploid form. In other eukaryotic species, however, the haploid phase may dominate or the phases may be equally developed. Even though an alternation between haploid and diploid forms is fundamental to sexual reproduction in eukaryotes, relatively little is known about the evolutionary forces that influence the dominance of haploidy or diploidy. An obvious genetic factor that might result in selection for a dominant diploid phase is heterozygote advantage, since only the diploid phase can be heterozygous. In this paper, I analyze a model designed to determine whether heterozygote advantage could lead to the evolution of a dominant diploid phase. The main result is that heterozygote advantage can lead to an increase in the dominance of the diploid phase, but only if the diploid phase is already sufficiently dominant. Because the diploid phase is unlikely to be increased in organisms that are primarily haploid, I conclude that heterozygote advantage is not a sufficient explanation of the dominance of the diploid phase in higher plants and animals.}, } @article {pmid1404401, year = {1992}, author = {Kostrzewa, M and Zetsche, K}, title = {Large ATP synthase operon of the red alga Antithamnion sp. resembles the corresponding operon in cyanobacteria.}, journal = {Journal of molecular biology}, volume = {227}, number = {3}, pages = {961-970}, doi = {10.1016/0022-2836(92)90238-f}, pmid = {1404401}, issn = {0022-2836}, mesh = {Amino Acid Sequence ; Bacterial Proteins/chemistry/genetics ; Base Sequence ; Blotting, Northern ; Chloroplasts/enzymology ; Cloning, Molecular ; Cyanobacteria/enzymology/*genetics ; Molecular Sequence Data ; Multigene Family/*genetics ; Open Reading Frames ; Operon/*genetics ; Proton-Translocating ATPases/chemistry/*genetics ; Regulatory Sequences, Nucleic Acid ; Rhodophyta/enzymology/*genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {The large plastid ATP synthase operon of the multicellular red alga Antithamnion sp. was cloned and the sequence of six ATPase genes determined. The operon resembles more the one from cyanobacteria than the ATP synthase operon of the chloroplast genome. The gene order is atpI, H, G, F, D and A, coding for the ATPase subunits a, c, b', b, delta and alpha, respectively. In green plants, the genes atpG and atpD are located in the nucleus. Unlike the situation in three published cyanobacterial ATP synthase operons, atpC, coding for the gamma subunit, is not a part of the rhodoplast operon. A single 4.5 kb transcript was detected with atpG, F, D and A gene probes that could span the whole operon, but no transcript could be detected with atpI and atpH probes. The end of an open reading frame preceding the atp genes shows remarkable homology to elongation factor TS from Escherichia coli. Behind the ATPase cluster, two open reading frames were detected that are not homologous to any known chloroplast gene. One of them may code for a transport protein of unknown specificity. Gene arrangement and sequence comparisons support the hypothesis of a polyphyletic origin of rhodoplasts and chloroplasts.}, } @article {pmid1297348, year = {1992}, author = {Johnston, RN and Pai, SB and Pai, RB}, title = {The origin of the cancer cell: oncogeny reverses phylogeny.}, journal = {Biochemistry and cell biology = Biochimie et biologie cellulaire}, volume = {70}, number = {10-11}, pages = {831-834}, doi = {10.1139/o92-130}, pmid = {1297348}, issn = {0829-8211}, mesh = {Animals ; *Biological Evolution ; Cell Division/genetics ; Cell Transformation, Neoplastic/*genetics ; Genes, Tumor Suppressor ; Growth Substances/physiology ; Humans ; Proto-Oncogenes ; }, abstract = {The formulation in 1874 of the biogenetic law by Ernst Haeckel as "ontogeny recapitulates phylogeny" emphasized the structural similarities detected in metazoans between their developmental and ancestral forms. More recently, many workers have independently commented on the similarities observed between the behaviours displayed by dedifferentiated cancer cells and their embryonic precursors. This review will explore a possible linkage between these disparate observations and will suggest that cancer cells behave in ways that are reminiscent of primitive eukaryotic cells. In particular, we suggest that the acquisition of a multicellular level of organization during early metazoan evolution required a critical and difficult change in growth strategy as germ line and somatic cells became distinct. Whereas unicellular free living eukaryotes follow a simple strategy of rapid division as long as conditions permit, the elaboration of powerful growth inhibitory pathways must have been necessary in primitive multicellular organisms to enable some but not all sister cells to stop dividing, even under conditions of nutrient abundance. This limitation on cellular growth would than have permitted the appearance of tissues and organs with differentiated characteristics, ultimately enabling the enhanced survival of the meiotic lineage. Cancer cells might therefore be considered to represent, with their loss of tumor suppressor inhibitory activity and elevation of oncogene stimulatory activity, a reversion to a more primitive evolutionary state capable of indeterminate growth at the expense of the host. By this analogy, the growth phenotypes displayed by cancer cells, embryonic cells, and free-living eukaryotes are fundamentally similar.}, } @article {pmid1518815, year = {1992}, author = {Ma, M and Eaton, JW}, title = {Multicellular oxidant defense in unicellular organisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {89}, number = {17}, pages = {7924-7928}, pmid = {1518815}, issn = {0027-8424}, support = {AI-25625/AI/NIAID NIH HHS/United States ; }, mesh = {Biological Evolution ; Catalase/*metabolism ; Escherichia coli/*enzymology/growth & development ; Hydrogen Peroxide/*toxicity ; Oxidation-Reduction ; Streptococcus/metabolism ; }, abstract = {Although catalase is thought to be a major defense against hydrogen peroxide (H2O2), the catalase activity within individual Escherichia coli fails to protect against exogenous H2O2. Contrary to earlier reports, we find that dilute suspensions of wild-type and catalase-deficient E. coli are identical in their sensitivity to H2O2, perhaps because even wild-type, catalase-positive E. coli cannot maintain an internal/external concentration gradient of this highly diffusible oxidant. However, concentrated suspensions or colonies of catalase-positive E. coli do preferentially survive H2O2 challenge and can even cross-protect adjacent catalase-deficient organisms. Furthermore, high-density catalase-positive--but not catalase-negative--E. coli can survive and multiply in the presence of competitive, peroxide-generating streptococci. These observations support the concept that bacterial catalase may defend colonial, but not individual, E. coli against environmental H2O2. Group protection by the activity of enzymes that mitigate oxidative stress may have been a driving force in the evolution of multicellular organisms.}, } @article {pmid1378585, year = {1992}, author = {Ottilie, S and Raulf, F and Barnekow, A and Hannig, G and Schartl, M}, title = {Multiple src-related kinase genes, srk1-4, in the fresh water sponge Spongilla lacustris.}, journal = {Oncogene}, volume = {7}, number = {8}, pages = {1625-1630}, pmid = {1378585}, issn = {0950-9232}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Biological Evolution ; CSK Tyrosine-Protein Kinase ; Cloning, Molecular ; Genes, src/*genetics ; Molecular Sequence Data ; Multigene Family/*genetics ; Oligodeoxyribonucleotides/genetics ; Polymerase Chain Reaction ; Porifera/*genetics ; Protein-Tyrosine Kinases/chemistry/*genetics ; Proto-Oncogene Proteins pp60(c-src)/chemistry/*genetics ; Restriction Mapping ; src-Family Kinases ; }, abstract = {In one of the simplest metazoan organisms, the sponge Spongilla lacustris, at least four different src-related kinase genes (srk1-4) are expressed, all of which show a high degree of similarity to the c-src genes of vertebrates. Whereas srk2 and srk3 are clearly unrelated at the nucleic acid level, srk1 and srk4 share identical sequences in the 5' parts of their cDNAs. The cloning of several primer extension clones and genomic polymerase chain reaction experiments confirmed the hypothesis of an alternative splicing of tandemly arranged carboxy-terminal parts of srk1 and srk4. The genomic sequence encoding both proteins was found to be interrupted at the splice point by an intron which is located in the same position as one of the introns in the chicken src gene, which is the only gene conserved in invertebrates and vertebrates. All four srk genes are expressed in adult sponges as mRNA transcripts of about 2.2 kb. Tyrosine kinase activity of a src-related kinase could be detected in adult sponges but not in their resting form (gemmulae), and may reflect the activity of the srk protein products. Spongilla lacustris is the simplest organism from which a protein tyrosine kinase gene has been isolated. The presence of at least four such genes in the evolutionary ancient and primitive phylum Porifera suggests that tyrosine kinase genes arose concomitantly with or shortly after the appearance of multicellular organisms and that their activity may be involved in aggregation and cell-cell recognition.}, } @article {pmid1642852, year = {1992}, author = {Koha, M and Brismar, B and Wikström, B}, title = {DNA content in primary tumours and lymph node metastases in colorectal adenocarcinoma.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {100}, number = {7}, pages = {640-644}, doi = {10.1111/j.1699-0463.1992.tb03979.x}, pmid = {1642852}, issn = {0903-4641}, mesh = {Adenocarcinoma/*genetics/pathology ; Adult ; Aged ; Aged, 80 and over ; *Aneuploidy ; Colorectal Neoplasms/*genetics/pathology ; DNA, Neoplasm/analysis ; Female ; Humans ; Lymphatic Metastasis/*genetics/pathology ; Male ; Middle Aged ; }, abstract = {In 18 consecutive patients operated on for colorectal carcinoma of Dukes' stage C, the DNA patterns were determined in multiple samples of the primary tumours and in all detected lymph node metastases. Single-cell microspectrophotometry on Feulgen-stained smears of fine-needle aspirates was used. When the most aggressive DNA pattern was considered representative, 12 primary tumours (67%) were designated as aneuploid. The frequency of aneuploidy among the metastases was almost the same (63%). In 15 cases (83%) the DNA patterns displayed by the metastatic lymph nodes were also found in the corresponding primary tumour, while in the remaining three cases (17%) the DNA pattern in the lymph node metastases was not seen in any of the multiple samples from the primary tumour. The observed tumour DNA heterogeneity may reflect either the multicellular origin of the tumour cells or the continuous evolution and progression of a neoplasm of unicellular origin, and may partly explain the dissimilarities between the DNA patterns of the primary tumour and the lymph node metastases. Biopsy samples from a number of metastatic lymph nodes are therefore required to ensure representativeness and to permit an adequate analysis of the prognostic role of the DNA ploidy status in lymph node metastases from colorectal cancer.}, } @article {pmid1626955, year = {1992}, author = {Kohno, N and Ichikawa, G and Kawasaki, K and Kawaida, M and Ohnuma, T}, title = {[Combination chemotherapy of solid tumor--effects of hyaluronidase on doxorubicin (DXR) penetration into multicellular tumor spheroids (MTS)].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {19}, number = {7}, pages = {981-986}, pmid = {1626955}, issn = {0385-0684}, mesh = {Carcinoma, Squamous Cell/pathology ; Cell Survival/drug effects ; Doxorubicin/pharmacokinetics/*pharmacology ; Drug Synergism ; Humans ; Hyaluronoglucosaminidase/*pharmacology ; Laryngeal Neoplasms/pathology ; Lung Neoplasms/pathology ; Tumor Cells, Cultured/*drug effects/metabolism ; }, abstract = {We have studied the effects of hyaluronidase (HYD) on the penetration and cell kill effect of doxorubicin (DXR) using multicellular tumor spheroids (MTS). MTS of approximately 500 microns in diameter were prepared by liquid over lay culture technique from PC-10 lung and HEp-2 laryngeal squamous carcinoma cell lines. Cells in MTS and monolayer were exposed for various durations to HYD, followed by 1 hr, rest interval, and by 1 hr. exposure to DXR. MTS and monolayer cells were then trypsinized to a single cell suspension and subjected to clonogenic assay. For PC-10 MTS, pretreatment with HYD for 24 hr. resulted in approximately 10-fold increases in DXR cell kill effects as compared to DXR alone. HEp-2 MTS were more sensitive to HYD pretreatment. Thus, 1 hr. exposure to HYD produced approximately 4-fold increases in DXR-induced cell lethality. Fluorescent microscopic study revealed that 1hr. exposure of MTS to DXR produced DXR fluorescence only 1-2 outer layer of MTS. When MTS were pretreated with HYD, there was an enhanced penetration of DXR fluorescence into the MTS core. HYD-induced enhancement of DXR penetration and its cell kill effect was dependent on the exposure time and tumor cell origin.}, } @article {pmid1606667, year = {1992}, author = {Eid, H and Larson, DM and Springhorn, JP and Attawia, MA and Nayak, RC and Smith, TW and Kelly, RA}, title = {Role of epicardial mesothelial cells in the modification of phenotype and function of adult rat ventricular myocytes in primary coculture.}, journal = {Circulation research}, volume = {71}, number = {1}, pages = {40-50}, doi = {10.1161/01.res.71.1.40}, pmid = {1606667}, issn = {0009-7330}, support = {HL-36141/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cells, Cultured ; Cytological Techniques ; Epithelial Cells ; Epithelium/physiology ; Heart/physiology ; Heart Ventricles ; Myocardium/*cytology ; Pericardium/cytology/*physiology ; Phenotype ; Rats ; }, abstract = {Adult rat ventricular myocytes undergo a well-documented sequence of phenotypic changes during adaptation to primary culture. However, we observed that coculture of myocytes with a specific subset of nonmyocyte cardiac cells could slow and even reverse the process of adaptation. These nonmyocyte cells were isolated and identified by immunohistochemical and ultrastructural criteria as being of epicardial mesothelial origin. When added to long-term primary cultures of adult ventricular myocytes, epicardial mesothelial cells appeared to induce myofibrillar arrays that were more organized than those seen in noncocultured myocytes; these changes that occurred were concurrent with the appearance of large amplitude contractions and multicellular synchronous beating that was facilitated by gap junctions between myocytes and epicardial mesothelial cells. The changes in morphology and function were accompanied by a marked increase in beta-myosin heavy chain isoform transcription in cocultured myocytes, a return to the ratio of cardiac to skeletal alpha-actin expected in adult rat myocardium, and a much reduced expression of smooth muscle alpha-actin. These changes in myocyte phenotype and function appeared to require epicardial cell-myocyte contact, or close apposition, because media conditioned by epicardial mesothelial cells alone or in coculture had no effect. Thus, these rapid and reversible changes in myocyte ultrastructure, function, and gene expression may provide a useful in vitro model with which to study the mechanism responsible for regulating the plasticity of ventricular myocyte phenotype and the role of specific cell-cell interactions.}, } @article {pmid1513272, year = {1992}, author = {Aboitiz, F}, title = {Mechanisms of adaptive evolution. Darwinism and Lamarckism restated.}, journal = {Medical hypotheses}, volume = {38}, number = {3}, pages = {194-202}, doi = {10.1016/0306-9877(92)90093-r}, pmid = {1513272}, issn = {0306-9877}, mesh = {*Adaptation, Physiological ; Animals ; *Biological Evolution ; Environment ; *Models, Biological ; Selection, Genetic ; }, abstract = {This article discusses the conceptual basis of the different mechanisms of adaptive evolution. It is argued that only two such mechanisms may conceivably exist, Lamarckism and Darwinism. Darwinism is the fundamental process generating the diversity of species. Some aspects of the gene-centered approach to Darwinism are questioned, since they do not account for the generation of biological diversity. Diversity in biological design must be explained in relation to the diversity of interactions of organisms (or other higher-level units) with their environment. This aspect is usually overlooked in gene-centered views of evolution. A variant of the gene-selectionist approach has been proposed to account for the spread of cultural traits in human societies. Alternatively, I argue that social evolution is rather driven by what I call pseudo-Lamarckian inheritance. Finally, I argue that Lamarckian and pseudo-Lamarckian inheritance are just special cases of faithful replication which are found in the development of some higher-order units, such as multicellular organisms and human societies.}, } @article {pmid1319575, year = {1992}, author = {Powell, JA and Galindo, J and Firtel, RA}, title = {A negative transcriptional control region of a developmentally-regulated gene co-localizes with the origin of replication of an endogenous plasmid in Dictyostelium.}, journal = {Nucleic acids research}, volume = {20}, number = {11}, pages = {2795-2802}, pmid = {1319575}, issn = {0305-1048}, mesh = {Animals ; Base Sequence ; Cyclic AMP/biosynthesis ; *DNA Replication ; DNA, Fungal/genetics ; Dictyostelium/*genetics ; *Gene Expression Regulation, Fungal ; *Genes, Fungal ; Molecular Sequence Data ; *Plasmids ; Promoter Regions, Genetic ; *Regulatory Sequences, Nucleic Acid ; Restriction Mapping ; Transcription, Genetic ; }, abstract = {The endogenous nuclear plasmid Ddp1 from the wild-type Dictyostelium discoideum strain NC4 has been cloned, its origin of replication has been localized, and plasmid-encoded genes have been mapped that are preferentially expressed during growth or development. Here we present an analysis of the regulation of the Ddp1-encoded gene d5, which, in wild-type cells, is expressed only during the multicellular stages of development. In this study, we show that sequences 3' to the d5 coding region are required to suppress constitutive expression of d5 from aberrant transcriptional start sites and that this regulatory region acts at a distance and in an orientation-independent manner. The cis-acting negative regulatory element(s) necessary for repression of aberrant d5 expression is either very tightly linked or identical to sequences required for extrachromosomal replication, such that all 3' deletions that cause constitutive d5 expression result in the integration of the plasmid into the D. discoideum genome. Placing d5 (without the 3' regions containing the Ddp1 origin) on an extrachromosomal vector based on another endogenous plasmid (Ddp2) did not restore proper transcriptional regulation, suggesting that an extrachromosomal environment alone is not sufficient to confer proper transcriptional regulation to d5.}, } @article {pmid1528155, year = {1992}, author = {Cotton, DW and Cross, SS}, title = {On the origins of mitosis and why it is involved in cancer.}, journal = {Medical hypotheses}, volume = {38}, number = {2}, pages = {118-119}, doi = {10.1016/0306-9877(92)90083-o}, pmid = {1528155}, issn = {0306-9877}, mesh = {Animals ; Biological Evolution ; Cell Division ; DNA Damage ; *DNA Replication ; Humans ; *Mitosis ; Models, Biological ; Mutation ; Neoplasms/genetics/*pathology ; Oncogenes ; }, abstract = {It is suggested that mitosis arose in evolution as a mechanism for 'excreting' damaged DNA (mutations). The mechanism for excretion involved replication of the DNA and was thus a pre-adaptation that could be used for cell replication. In multicellular organisms the mutated cells cannot always be lost and may persist as neoplasms.}, } @article {pmid1585174, year = {1992}, author = {Knoll, AH}, title = {The early evolution of eukaryotes: a geological perspective.}, journal = {Science (New York, N.Y.)}, volume = {256}, number = {5057}, pages = {622-627}, doi = {10.1126/science.1585174}, pmid = {1585174}, issn = {0036-8075}, mesh = {*Biological Evolution ; Cyanobacteria ; Eukaryota ; *Eukaryotic Cells ; Fossils ; Geological Phenomena ; *Geology ; Mitochondria ; Phylogeny ; }, abstract = {Molecular phylogenies of eukaryotic organisms imply patterns of biological and environmental history that can be tested against the geological record. As predicted by sequence comparisons, Precambrian rocks show evidence of episodic increases in biological diversity and atmospheric oxygen concentrations. Nonetheless, complete integration of the two records remains elusive and may require that the earliest macroscopic organisms be recognized as extinct experiments in eukaryotic multicellularity.}, } @article {pmid1556753, year = {1992}, author = {Sueoka, N}, title = {Directional mutation pressure, selective constraints, and genetic equilibria.}, journal = {Journal of molecular evolution}, volume = {34}, number = {2}, pages = {95-114}, pmid = {1556753}, issn = {0022-2844}, mesh = {Animals ; Base Composition ; *Biological Evolution ; DNA ; Gene Frequency ; Humans ; *Mutation ; *Selection, Genetic ; }, abstract = {Rates of substitution mutations in two directions, v [from an A-T or T-A nucleotide pair (AT-pair) to a G-C or C-G nucleotide pair (GC-pair)] and u [from a GC-pair to an AT-pair], are usually not the same. The net effect, v/(u + v), has previously been defined as directional mutation pressure (mu D), which explains the wide interspecific variation and narrow intragenomic heterogeneity of DNA G + C content in bacteria. In this article, first, a theory of the evolution of DNA G + C content is presented that is based on the equilibrium among three components: directional mutation pressure, DNA G + C content, and selective constraints. According to this theory, consideration of both u and v as well as selective constraints is essential to explain the molecular evolution of the DNA base composition and sequence. Second, the theory of directional mutation pressure is applied to the analysis of the wide intragenomic heterogeneity of DNA G + C content in multicellular eukaryotes. The theory explains the extensive intragenomic heterogeneity of G + C content of higher eukaryotes primarily as the result of the intragenomic differences of directional mutation pressure and selective constraints rather than the result of positive selections for functional advantages of the DNA G + C content itself.}, } @article {pmid1730568, year = {1992}, author = {Rowley, DR}, title = {Characterization of a fetal urogenital sinus mesenchymal cell line U4F: secretion of a negative growth regulatory activity.}, journal = {In vitro cellular & developmental biology : journal of the Tissue Culture Association}, volume = {28A}, number = {1}, pages = {29-38}, pmid = {1730568}, issn = {0883-8364}, support = {DK39779/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Antibodies ; Cell Line ; Connective Tissue/embryology ; *Connective Tissue Cells ; Culture Media ; Culture Techniques/methods ; DNA Replication ; Epithelial Cells ; Epithelium/drug effects ; Fetus ; Growth Inhibitors/*biosynthesis/isolation & purification/pharmacology ; Intermediate Filament Proteins/analysis ; Organ Culture Techniques/methods ; Rats ; Rats, Inbred Strains ; Thymidine/metabolism ; Tritium ; Urinary Bladder ; Urogenital System/cytology/embryology ; Vimentin/analysis ; }, abstract = {Mesenchymal cell lines derived from fetal rat urogenital sinus organ cultures have been characterized to establish an in vitro system for addressing growth and differentiation regulatory factors involved in mesenchymal-epithelial interactions during prostate morphogenesis. A continuous cell line was developed and designated U4F. Immunocytochemical analysis showed vimentin intermediate filament content confirming a mesenchymal origin. Previous studies with urogenital sinus organ cultures have reported the expression of a negative growth activity, which is stimulatory to protein synthesis and secretion and alters phenotypic morphology of NBT-II bladder epithelial cells. Subconfluent and confluent U4F monolayers did not produce this growth inhibitory activity. Foci of stacked cells were observed 3 wk postconfluency, which evolved into multicellular spheroids. The negative growth activity was expressed in the conditioned medium coordinate with spheroid formation. Transplanted spheroids continued to express the growth inhibitory activity. Morphologic analysis of spheroids showed a cellular capsule and a core of extracellular matrix. A continuous cell strain (U4F1) with altered phenotypic properties, arose spontaneously from long-term U4F cultures. The U4F1 cell strain did not form spheroids, yet expressed the negative growth activity constitutively in monolayer culture. Analyses of physicochemical, immunological, and biological properties showed the activity is identical in conditioned media from urogenital sinus organ cultures, U4F spheroids, and U4F1 monolayers. Based on the combined properties, this activity cannot be ascribed to previously characterized negative growth factors. The establishment of this mesenchymal cell culture system will aid in the further identification of paracrine-acting growth and differentiation regulatory factors secreted by fetal mesenchyme.}, } @article {pmid1552843, year = {1992}, author = {Larson, A and Kirk, MM and Kirk, DL}, title = {Molecular phylogeny of the volvocine flagellates.}, journal = {Molecular biology and evolution}, volume = {9}, number = {1}, pages = {85-105}, doi = {10.1093/oxfordjournals.molbev.a040710}, pmid = {1552843}, issn = {0737-4038}, support = {GM27215/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Biological Evolution ; Chlorophyta/classification/*genetics ; Chromosome Aberrations/genetics ; Molecular Sequence Data ; *Phylogeny ; RNA, Ribosomal/*genetics ; Sequence Homology, Nucleic Acid ; Volvocida/classification/*genetics ; }, abstract = {Phylogenetic studies of approximately 2,000 bases of sequence from the large and small nuclear-encoded ribosomal RNAs are used to investigate the origins of the genus Volvox. The colonial and multicellular genera currently placed in the family Volvocaceae form a monophyletic group that is significantly closer phylogenetically to Chlamydomonas reinhardtii than it is to the other unicellular green flagellates that were tested, including Chlamydomonas eugametos, Chlorella pyrenoidosa, and Haematococcus lacustris. Statistical analysis of 251 phylogenetically informative nucleotide positions rejects the "volvocine lineage" hypothesis, which postulates a monophyletic evolutionary progression from unicellular organisms (such as Chlamydomonas), through colonial organisms (e.g., Gonium, Pandorina, Eudorina, and Pleodorina) demonstrating increasing size, cell number, and tendency toward cellular differentiation, to multicellular organisms having fully differentiated somatic and reproductive cells (in the genus Volvox). The genus Volvox appears not to be monophyletic. Volvox capensis falls outside a lineage containing other representatives of Volvox (V. aureus, V. carteri, and V. obversus), and both of these Volvox lineages are more closely related to certain colonial genera than they are to each other. This implies either a diphyletic origin of Volvox from different colonial volvocacean ancestors, a phylogenetic derivation of some of the colonial genera from a multicellular (i.e., Volvox) ancestor, or both. Considered together with previously published observations, these results suggest that the different levels of organizational and developmental complexity found in the Volvocaceae represent alternative stable states, among which evolutionary transitions have occurred several times during the phylogenetic history of this group.}, } @article {pmid1473528, year = {1992}, author = {Corocleanu, M}, title = {Prospects for preneoplasia immuno-detection and cancer immuno-prevention.}, journal = {European journal of gynaecological oncology}, volume = {13}, number = {6}, pages = {486-489}, pmid = {1473528}, issn = {0392-2936}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/immunology/*prevention & control ; Female ; Genital Neoplasms, Female/immunology/*prevention & control ; Humans ; Precancerous Conditions/diagnosis/*immunology ; }, abstract = {The three traditional modalities of cancer treatment: surgery, radio- and chemotherapy, even when applied in optimal fashion, leave over 50% of incurable patients, because of the metastatic disease. Hence the importance of preventive methods in cancer, by directing attention to the detection and treatment of preneoplasia. Focal preneoplastic lesions have been observed prior to the appearance of malignant epithelial tissues. The phenotypic patterns of preneoplasia seem to be as varied as those of neoplasia. In the frame of persistent multicellular hyperplasia, the appearance of enzyme-altered foci is supposed to be related to the origin of neoplasia, and in this sense these lesions can be considered pre-neoplasia. If there is any immune reaction to the non-self promoted by these lesions, their detection and their enhancement or induction by a vaccine would be a cancer immuno-prevention. Preliminary experiments and clinical pilot studies have shown a specific host-resistance to a pharmaceutical placental suspension (PS), when injected intradermally (DTHS-reactivity test) in patients with clinical conditions having, as histopathological substratum, a cellular adaptive (reactive) or neoplastic proliferation. Boosting this reaction by an adjuvant (BCG, corynebacterium parvum, etc.) would be an immunotherapeutic approach to cancer, as adjunct to standard treatments and in preneoplastic-bearing patients an immuno-preventive method in cancer. In vitro studies have shown that a glycoprotein of MW 40 kDa (P40), from an extract of placental suspension (PS) is recognized by patients' serum, (Ouchterlony's technique). The monospecific rabbit antiserum (MRA) raised to P40 glycoprotein also reacts with the serum of patients with positive DTHS reactions to PS.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid1467450, year = {1992}, author = {Blazsek, I}, title = {Innate chaos: I. The origin and genesis of complex morphologies and homeotic regulation.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {46}, number = {5-7}, pages = {219-235}, doi = {10.1016/0753-3322(92)90085-l}, pmid = {1467450}, issn = {0753-3322}, mesh = {Cell Transformation, Neoplastic/genetics ; Gene Expression Regulation/*genetics ; Hematopoietic Stem Cells/microbiology ; Humans ; Morphogenesis ; }, abstract = {The genesis of complex morphologies is an inherent property of all dynamically expanding natural systems. In the inorganic and prebiotic world, chaotic movement of quantitable particles results in formation of ordered streamlined structures or micelles close to phase boundaries. In the course of chemical and colloid crystallization or development of living organisms, complex morphologies emerge, due to unusual chaotic attraction, diffusion limited aggregation (DLA) and multifractal organization suggesting that common mechanisms direct the morphogenesis in a wide range of natural systems. The development of a multicellular organism from a single fertilized oocyte requires intensive clonal proliferation sequential determinations and the organization of terminally differentiated cells in morphologically stable homeostatic functional units. Comparative data on insect and vertebrate embryogenesis revealed that the spatial organization of the developing body is orchestrated by several mechanisms: maternal effect genes or cell position specify the initial polarities and the main axes, while metameric segmentation, intrasegment identity and cell fate are determined by the programmed expression of morphogenetic determinants. They include evolutionarily conserved DNA binding proteins containing homeobox or pair-box sequences, endogenous ligands, activating specific nuclear hormone receptors, and humoral growth factors acting via specific membrane receptors and more ubiquitous transducing pathways. Morphogenetic regulators form intratissual gradients and demark fields required for the correct realization of the developmental programme. It has been recognized that the cell's freedom is limited to stringent developmental choices that in the end results in the formation of coherent cell colonies, many of them displaying chaotic behaviour. The linkage between embryonic regulation and adult tissue differentiation is not completely elucidated, however, data are emerging to show that several morphogenetic regulators may function throughout life in different human tissues. Genetically transmissible deletions or acquired impairments likely contribute to malignant tissue growth. Diffusible morphogenetic regulators may reverse the malignant phenotype in some cases and induce clinical remission. Further work is needed, however, to identify the dominant components of physiological regulatory networks and to understand what hierarchical organization and chaotic behaviour represent in order to elaborate new combined therapeutic protocols.}, } @article {pmid1451234, year = {1992}, author = {Thomsen, LL and Baguley, BC and Wilson, WR}, title = {Nitric oxide: its production in host-cell-infiltrated EMT6 spheroids and its role in tumour cell killing by flavone-8-acetic acid and 5,6-dimethylxanthenone-4-acetic acid.}, journal = {Cancer chemotherapy and pharmacology}, volume = {31}, number = {2}, pages = {151-155}, pmid = {1451234}, issn = {0344-5704}, mesh = {Adenocarcinoma/*drug therapy/metabolism ; Animals ; Antineoplastic Agents/*therapeutic use ; Flavonoids/*therapeutic use ; Mammary Neoplasms, Experimental/*drug therapy/metabolism ; Nitric Oxide/*metabolism ; Tumor Cells, Cultured ; Tumor Stem Cell Assay ; Xanthenes/*therapeutic use ; *Xanthones ; }, abstract = {Flavone-8-acetic acid (FAA) and its more dose-potent analogue 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA), appear to exert their antitumor effects through vascular and other host-mediated mechanisms and are known to induce the synthesis of nitric oxide by murine macrophages. We investigated the role of nitric oxide in the cytotoxic effects of these drugs in host-cell-infiltrated spheroids. EMT6 murine mammary adenocarcinoma cells were grown in culture to produce multicellular spheroids in vitro spheroids), which were then inoculated i.p. into mice. After 6 days the spheroids were removed ex vivo spheroids). Exposure to FAA (890 microM) and 5,6-MeXAA (80 microM) in vitro for 20 h increased nitrite concentrations to 6.7 and 9.7 nmol/spheroid, respectively, as compared with 0.7 nmol/spheroid in the absence of drug. FAA and 5,6-MeXAA did not increase nitrite production in in vitro spheroids in cells obtained by peritoneal lavage. However, mixed cultures of in vitro spheroids and peritoneal cells treated with 5,6-MeXAA produced nitrite (2.4 nmol/spheroid), indicating that interactions between host cells and tumour cells were important for induction. The effects of these drugs on ex vivo spheroids were prevented by co-incubation with NG-monomethyl-L-arginine, indicating that nitrite originated from the oxidation of L-arginine to nitric oxide. Cell sorting of disaggregated spheroids into EMT6 cells and Mac-1-positive macrophage populations indicated that both of these cell populations could be induced to synthesise nitric oxide by subsequent incubation with 5,6-MeXAA. Incubation of ex vivo spheroids with FAA and 5,6-MeXAA decreased the clonogenicity of EMT6 cells, and this effect was wholly (FAA) or partially (5,6-MeXAA) reversed by the presence of NG-monomethylarginine (250 microM). FAA and 5,6-MeXAA may therefore exert some of their cytotoxic effects on tumour cells through the production of nitric oxide.}, } @article {pmid1804739, year = {1991}, author = {Tirlapur, UK and Gross, J and Nanjundiah, V}, title = {Spatial variation of sequestered calcium in the multicellular stage of Dictyostelium discoideum as assayed by chlortetracycline fluorescence.}, journal = {Differentiation; research in biological diversity}, volume = {48}, number = {3}, pages = {137-146}, doi = {10.1111/j.1432-0436.1991.tb00252.x}, pmid = {1804739}, issn = {0301-4681}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Calcium/*metabolism ; Chlortetracycline ; Dictyostelium/cytology/*growth & development/metabolism ; Kinetics ; Microscopy, Fluorescence/methods ; Microscopy, Phase-Contrast ; }, abstract = {We have used chlortetracycline (CTC) as a fluorescent probe to detect the distribution of sequestered calcium in multicellular stages of Dictyostelium discoideum. Tips of late aggregates, slugs and early culminating masses fluoresce very strongly. Most of the fluorescence is intracellular in origin and emanates from a small number of intense punctate sources. The sources correspond in part to autophagic vacuoles vis. neutral-red staining, acidic digestive vesicles, and may also include intracellular organelles; cytoplasmic fluorescence is much weaker in comparison. The level of fluorescence drops in the middle portion of slugs and rises again in the posteriormost region, though not to as high a level as in the tip. This holds good irrespective of whether CTC is applied only in the neighbourhood of the aggregate centre, only in the aggregate periphery, or to the whole aggregate. We infer that there must be a good deal of mixing in the stages leading from aggregation to slug formation; thus the serial order in which cells enter an aggregate does not bear any relation to their ultimate fates. The other implication of our study is that calcium sequestration is much more extensive in prestalk and anterior-like cells than in prespore cells. These findings are discussed with regard to possible implications for pattern formation.}, } @article {pmid1783297, year = {1991}, author = {Hastings, IM}, title = {Germline selection: population genetic aspects of the sexual/asexual life cycle.}, journal = {Genetics}, volume = {129}, number = {4}, pages = {1167-1176}, pmid = {1783297}, issn = {0016-6731}, mesh = {Animals ; Biological Evolution ; Genes, Dominant ; *Germ Cells ; Models, Genetic ; Mutation ; Recombination, Genetic ; Reproduction/*genetics ; Reproduction, Asexual/*genetics ; *Selection, Genetic ; }, abstract = {Population geneticists make a distinction between sexual and asexual organisms depending on whether individuals inherit genes from one or two parents. When individual genes are considered, this distinction becomes less satisfactory for multicellular sexual organisms. Individual genes pass through numerous asexual mitotic cell divisions in the germline prior to meiosis and sexual recombination. The processes of mitotic mutation, mitotic crossing over, and mitotic gene conversion create genotypic diversity between diploid cells in the germline. Genes expressed in the germline whose products affect cell viability (such as many "housekeeping" enzymes) may be subjected to natural selection acting on this variability resulting in a non-Mendelian output of gametes. Such genes will be governed by the population genetics of the sexual/asexual life cycle rather than the conventional sexual/Mendelian life cycle. A model is developed to investigate some properties of the sexual/asexual life cycle. When appropriate parameter values were included in the model, it was found that mutation rates per locus per gamete may vary by a factor of up to 100 if selection acts in the germline. Sexual/asexual populations appear able to evolve to a genotype of higher fitness despite intervening genotypes of lower fitness, reducing the problems of underdominance and Wright's adaptive landscape encountered by purely sexual populations. As might be expected this ability is chiefly determined by the number of asexual mitotic cell divisions within the germline. The evolutionary consequences of "housekeeping" loci being governed by the dynamics of the sexual/asexual life cycle are considered.}, } @article {pmid1755818, year = {1991}, author = {Seamark, RF}, title = {The use of transgenic animals to study the role of growth factors in endocrinology.}, journal = {Bailliere's clinical endocrinology and metabolism}, volume = {5}, number = {4}, pages = {833-845}, doi = {10.1016/s0950-351x(10)80017-5}, pmid = {1755818}, issn = {0950-351X}, mesh = {Animals ; *Animals, Genetically Modified ; Endocrine Glands/*physiology ; Endocrine System Diseases ; Growth Substances/biosynthesis/genetics/*physiology ; Mice ; Mice, Transgenic ; }, abstract = {Transgenesis is identified as being of special interest in the study of growth factors where their multicellular origins and complex interactions make them particularly difficult to characterize using classical experimental approaches developed to investigate hormones originating in specialized cells in discrete glands. Through allowing molecular 'tinkering' in intact animals, transgenesis enables specific growth factors to be 'ablated or replaced' from specific tissues and organs and target cell response and impact of modulatory factors such as binding proteins to be explored in the intact animal. To the endocrinologist, the potential applications of such technology are legend. This chapter provides a brief overview of the technique and provides linkages to the rapidly developing body of literature in establishing transgenesis in growth factor research.}, } @article {pmid1896548, year = {1991}, author = {Nelson, JS}, title = {Selective photothermolysis and removal of cutaneous vasculopathies and tattoos by pulsed laser.}, journal = {Plastic and reconstructive surgery}, volume = {88}, number = {4}, pages = {723-731}, doi = {10.1097/00006534-199110000-00028}, pmid = {1896548}, issn = {0032-1052}, mesh = {Adult ; Child ; Female ; Hemangioma/*radiotherapy ; Humans ; *Laser Therapy ; Male ; Methods ; Middle Aged ; Skin Neoplasms/*radiotherapy ; *Tattooing ; }, abstract = {The evolution of the laser as a medical device has been a process of continued improvement. Research into increasing our understanding of the optical characteristics of skin has made it possible to concentrate not on the effects of any particular laser system, but on basic biologic and physical principles of laser-tissue interaction. The lasers available in the 1960s and 1970s offered few possibilities for modification. However, modern technology allows us to manipulate the physical characteristics of lasers and design them for specific therapeutic purposes. Selective photothermolysis relies on chromophore-specific absorption of a brief pulse of light to generate and confine heat to certain targets within the skin without nonspecific thermal damage to adjacent structures. Thermally mediated target alterations can be confined from the level of large multicellular tissue structures (e.g., blood vessels) to individual microscopic pigmented structures (e.g., tattoo pigment granules). The purpose of this report is to describe the current progress being made and to summarize the present theories for achieving increasing selective removal, without scarring or other skin textural changes, of cutaneous vasculopathies and tattoo pigment by pulsed laser.}, } @article {pmid1714884, year = {1991}, author = {Offner, FA and Ott, G and Povey, S and Knuechel, R and Preisler, V and Fuezesi, L and Klosterhalfen, B and Ruebben, H and Hofstaedter, F and Kirkpatrick, CJ}, title = {Characterization of the new bladder cancer cell line HOK-1: expression of transitional, squamous and glandular differentiation patterns.}, journal = {International journal of cancer}, volume = {49}, number = {1}, pages = {122-128}, doi = {10.1002/ijc.2910490123}, pmid = {1714884}, issn = {0020-7136}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Blood Group Antigens ; Carcinoma, Squamous Cell/chemistry/*pathology ; Carcinoma, Transitional Cell/chemistry/*pathology ; Cell Differentiation ; DNA, Neoplasm/analysis ; Female ; HLA Antigens/analysis ; Humans ; Isoenzymes/analysis ; Karyotyping ; Keratins/metabolism ; Microscopy, Electron ; Tumor Cells, Cultured/chemistry/*cytology ; Urinary Bladder Neoplasms/chemistry/*pathology ; }, abstract = {The new continuous cell line HOK-1 derived from a grade-III transitional-cell bladder carcinoma with foci of squamous and glandular differentiation was shown to retain this phenotypical heterogeneity for more than 45 passages in vitro. Electron microscopy revealed transitional as well as a considerable proportion of squamous carcinoma and adenocarcinoma cells. PAS-positive mucus was detected in numerous cells. These features were principally maintained when grown as multicellular spheroids and in nude mice. More pronounced signs of differentiation (i.e., expression of cytokeratins 10 and 11, formation of glandular structures) were found in xenograft tumours. Independently, cytokeratins 13, 18 and 19 were detected in vitro and in vivo, reflecting the urothelial origin. The line forms distinct colonies in soft agar, expresses Lewis-x and Lewis-y antigens and reacts with monoclonal antibodies (MAbs) against CEA, beta-HCG and URO-5. Cytogenetic analysis revealed several related clones with a rearrangement at chromosome 1 and loss of one X chromosome as common karyotypic changes in all clones. DNA content, as quantified by image analysis, showed a DNA stemline close to 2c. The new cell line HOK-1 can be used as an in vitro model to study the mechanisms of heterogeneous differentiation patterns in bladder cancer.}, } @article {pmid1934114, year = {1991}, author = {Winhauer, T and Jäger, S and Valentin, K and Zetsche, K}, title = {Structural similarities between psbA genes from red and brown algae.}, journal = {Current genetics}, volume = {20}, number = {1-2}, pages = {177-180}, pmid = {1934114}, issn = {0172-8083}, mesh = {Amino Acid Sequence ; Bacterial Proteins/genetics ; Cloning, Molecular ; Cyanobacteria/genetics ; Light-Harvesting Protein Complexes ; Molecular Sequence Data ; Phaeophyta/*genetics ; Photosynthetic Reaction Center Complex Proteins/*genetics ; Photosystem II Protein Complex ; Phylogeny ; Rhodophyta/*genetics ; Sequence Homology, Nucleic Acid ; }, abstract = {The single copy psbA genes from the multicellular red alga Antithamnion spec. and the brown alga Ectocarpus siliculosus have been cloned and sequenced and monocistronic transcripts have been detected. Both genes contain an insertion of 21 bp at the 3' end which was also found in cyanobacteria and which is absent in chloroplasts and the chlorophyll b-containing prochlorophyte Prochlorothrix hollandica. These findings are in agreement with the hypothesis of a polyphyletic origin of plastids. Plastids of red and brown algae appear to be closely related.}, } @article {pmid1780951, year = {1991}, author = {Baker, ME}, title = {Genealogy of regulation of human sex and adrenal function, prostaglandin action, snapdragon and petunia flower colors, antibiotics, and nitrogen fixation: functional diversity from two ancestral dehydrogenases.}, journal = {Steroids}, volume = {56}, number = {7}, pages = {354-360}, doi = {10.1016/0039-128x(91)90067-6}, pmid = {1780951}, issn = {0039-128X}, mesh = {Amino Acid Sequence ; Hormones/metabolism ; Hydroxysteroid Dehydrogenases/chemistry/*physiology ; Molecular Sequence Data ; Prostaglandins/physiology ; Steroids/*metabolism ; }, abstract = {Metabolism of steroid hormones by dehydrogenases is an important mechanism for regulating steroid hormone action. Analysis of recently reported amino acid sequences of 11 beta-hydroxysteroid dehydrogenase, 17 beta-hydroxysteroid dehydrogenase, and 3 alpha, 20 beta-hydroxysteroid dehydrogenase reveals that they are descended from a common ancestor. Unexpectedly, this superfamily of dehydrogenases has other interesting relatives: 15-hydroxyprostaglandin dehydrogenase, proteins found in nitrogen-fixing bacteria, and enzymes important in the synthesis of antibiotics. The novel lineage of these proteins and the actions of flavonoids in regulating gene transcription in nitrogen-fixing bacteria and mammals provide new insights into the evolution of regulation of gene transcription by intercellular signals in multicellular animals.}, } @article {pmid1757517, year = {1991}, author = {Demoulin, A and Jouan, C and Gerday, C and Dubois, M}, title = {Pregnancy rates after transfer of embryos obtained from different stimulation protocols and frozen at either pronucleate or multicellular stages.}, journal = {Human reproduction (Oxford, England)}, volume = {6}, number = {6}, pages = {799-804}, doi = {10.1093/oxfordjournals.humrep.a137431}, pmid = {1757517}, issn = {0268-1161}, mesh = {*Cryopreservation ; *Embryo Transfer ; Embryonic and Fetal Development/*physiology ; Female ; Fertilization in Vitro ; Humans ; Ovulation Induction/*methods ; Pregnancy/*statistics & numerical data ; Retrospective Studies ; }, abstract = {After in-vitro fertilization, 2161 supernumerary embryos were frozen with 1,2-propanediol and sucrose as cryoprotectants at either pronucleate or multicellular (2-6 blastomeres) stages. By the end of March 1990, 494 pronucleate stage embryos and 492 multicellular stage embryos had been thawed and 54 and 47% of them, respectively were considered suitable for transfer. Ongoing pregnancy and implantation rates were 17.9 and 10.7%, respectively for embryos frozen at the pronucleate stage and 5.5 and 4.7% for embryos frozen at the multicellular stage. Ovarian stimulation with human menopausal gonadotrophin (HMG) after pharmacological hypophysectomy with a gonadotrophin releasing hormone agonistic analogue (GnRHa) using a long protocol permitted us to freeze significantly more embryos per cycle (7.2 +/- 4.1) than stimulation with HMG and GnRHa in a short protocol (4.7 +/- 3.4) or stimulation with clomiphene citrate (CC) and HMG (2.7 +/- 1.9). Ongoing pregnancy rates after transfer during the stimulated cycles were similar for the three types of treatment (27.1, 27.3 and 32.1%, respectively). However, ongoing pregnancy rates after frozen-thawed embryo transfers were significantly higher when originating from GnRHa + HMG treatments (14.3 and 14.8%, respectively for long and short protocols) than when originating from CC + HMG treatment (5.6%). Embryo cryopreservation has permitted the ongoing pregnancy rate to increase from 28.4 to 36.9% (P less than 0.01) even though more than half of the embryos have not been thawed. We conclude that embryos obtained after stimulation with GnRHa + HMG and frozen at the pronucleate stage are more likely to result in a pregnancy.}, } @article {pmid1751448, year = {1991}, author = {Zimmerman, JL and Cohill, PR}, title = {Heat shock and thermotolerance in plant and animal embryogenesis.}, journal = {The New biologist}, volume = {3}, number = {7}, pages = {641-650}, pmid = {1751448}, issn = {1043-4674}, mesh = {Animals ; Body Temperature Regulation/*physiology ; Embryo, Mammalian/*physiology ; Embryo, Nonmammalian/*physiology ; Gene Expression Regulation ; Heat-Shock Proteins/physiology ; Hot Temperature/*adverse effects ; Seeds/*physiology ; }, abstract = {Although the strategies of early embryogenesis differ greatly among multicellular eukaryotes, there are certain parallels in structure, form, and function that cross even kingdom lines: the extreme heat sensitivity of zygotes and very early embryos, followed by the acquisition of thermotolerance during subsequent development, is one such parallel. The heat sensitivity may be so extreme that even moderate increases in temperature result in lethality (generally associated with the earliest phases of embryogenesis), or the effects may be less severe, resulting in defects in development but not in lethality. Mechanistically, and molecularly, these two forms of thermosensitivity appear to have different origins. On the one hand, outright lethality appears to result from an inability to induce heat shock genes and proteins; on the other hand, heat-induced developmental defects appear to result from an alteration in expression of non-heat shock genes and from a delay in the overall developmental program that generally accompanies the cell's response to heat shock. This review is focused on the developmental regulation of the heat shock response during early embryogenesis and on the impact of this regulation on the development of both animal and plant embryos. The two basic issues that we address here are (i) the expression of heat shock genes in the absence of heat shock during embryogenesis and (ii) the expression (or lack of expression) of heat shock genes after deliberate exposure of the embryos to heat shock and the consequences of this expression on its subsequent survival and development.}, } @article {pmid1718257, year = {1991}, author = {Barnekow, A}, title = {Functional aspects of a tyrosine kinase encoding protooncogene, the c-src gene.}, journal = {Behring Institute Mitteilungen}, volume = {}, number = {89}, pages = {67-73}, pmid = {1718257}, issn = {0301-0457}, mesh = {Animals ; Avian Sarcoma Viruses/genetics ; Cell Line ; *Genes, src ; Protein-Tyrosine Kinases/*genetics ; Proto-Oncogene Proteins pp60(c-src)/*genetics ; }, abstract = {To date the src gene family consists of at least 9 closely related protein tyrosine kinases belonging to the non-receptor type of kinases: c-src, c-yes, c-fgr, fyn, lyn, lck, hck, tkl and bkl. We have intensively studied the expression of the c-src gene during evolution and with respect to its possible functions in the processes of cellular differentiation and proliferation. From our results we conclude, that the c-src encoded tyrosine kinase could play a role in the development and/or maintenance of the multicellular organisation of primitive organisms like sponges or coelenterates. With respect to its tissue-specific expression pattern with neuronal cells always displaying elevated levels of pp60c-src and the observation that synaptophysin, the major constituent of the synaptic vesicle membrane protein, is phosphorylated by the c-src encoded tyrosinekinase in vitro and in intact synaptic vesicles, we suggest an essential role for pp60c-src in signal transduction pathways and/or axonal transport mechanisms in neurons.}, } @article {pmid1943129, year = {1991}, author = {Forsdyke, DR}, title = {Early evolution of MHC polymorphism.}, journal = {Journal of theoretical biology}, volume = {150}, number = {4}, pages = {451-456}, doi = {10.1016/s0022-5193(05)80439-4}, pmid = {1943129}, issn = {0022-5193}, mesh = {*Biological Evolution ; Immune System ; Major Histocompatibility Complex/*genetics ; Polymorphism, Genetic/*genetics/immunology ; Virus Physiological Phenomena ; }, abstract = {There is unwarranted satisfaction with the view that MHC polymorphism evolved because there was a selective advantage in having a variety of MHC proteins to bind a variety of peptide subsets for presentation to T cells. While this may, in part, explain its maintainance, polymorphism may have evolved initially to reject foreign virus "grafts". The possession of similar membranes promotes aggregation between "like" cells, but it also promotes aggregation between the cells and viruses which retain membrane components of their previous host. The selection pressure afforded by hostile virus "grafts" would favour cells which developed polymorphic membrane components (since "like" will not aggregate with "not-like"). This polymorphism would have evolved before the appearance of multicellular organisms. Thus, the evolution of modern immune systems would have been imposed upon pre-existing polymorphic systems. A path this evolution may have taken involves the development of mechanisms for intracellular distinction between self and not-self.}, } @article {pmid1886907, year = {1991}, author = {Gáti, I and Bergström, M and Muhr, C and Carlsson, J}, title = {Effects of the PAF-analog and -antagonist CV-6209 on cultured human glioma cell lines.}, journal = {Prostaglandins, leukotrienes, and essential fatty acids}, volume = {43}, number = {2}, pages = {103-110}, doi = {10.1016/0952-3278(91)90180-d}, pmid = {1886907}, issn = {0952-3278}, mesh = {Cell Division/*drug effects ; Cell Line ; Cell Survival/drug effects ; DNA Replication/drug effects ; Glioma ; Humans ; Kinetics ; Methionine/metabolism ; Neuroglia ; Platelet Activating Factor/*antagonists & inhibitors ; Pyridinium Compounds/*pharmacology ; Thymidine/metabolism ; }, abstract = {Cell lines of human glioma (U-343 MGa and U-251 MG) and human glia (U-533 CG) origin were cultured as monolayers and exposed to CV-6209, an alkyl-phospholipid analog and antagonist of platelet activating factor. This drug had very potent antiproliferative effects on the studied human glioma cell lines; IC50 was 0.9 microM after 48 h treatment and 0.2 microM after 2 weeks treatment. At these doses no growth inhibitory effect was noted on the normal glia cells. The effects on the glioma cells were reversible in the dose intervals, where cell proliferation, 3H-thymidine and 14C-methionine uptakes were greatly inhibited. The simultaneous administration of platelet activating factor [(R)PAF] did not influence the antiproliferative effects of CV-6209 on the cells cultured as monolayers. The structurally similar analog CV-3988 also had antiproliferative effects, although at 10 times higher concentration than CV-6209. Two other, structurally unrelated, PAF-antagonists (WEB-2086 and TCV-309) gave effects only at very high concentrations. The U-343 MGa cell line was also exposed to CV-6209 when growing as multicellular spheroids. The studies on the spheroid cultures also demonstrated good antitumoral effects with decreases of both the volume growth and the thymidine uptake. The simultaneous administration of (R)PAF reversed the inhibitory effect of CV-6209 on thymidine incorporation. This study demonstrates a strong antitumoral effect at low concentrations of CV-6209. The antiproliferative effects were probably primarily related to the ether-lipid structure and not to the PAF-antagonistic properties. The good antitumoral effect of CV-6209 on both monolayer and spheroid cultures and the possible PAF-antagonistic properties are discussed.}, } @article {pmid1903816, year = {1991}, author = {Leung, J and Sinclair, DA and Hayashi, S and Tener, GM and Grigliatti, TA}, title = {Informational redundancy of tRNA(4Ser) and tRNA(7Ser) genes in Drosophila melanogaster and evidence for intergenic recombination.}, journal = {Journal of molecular biology}, volume = {219}, number = {2}, pages = {175-188}, doi = {10.1016/0022-2836(91)90560-s}, pmid = {1903816}, issn = {0022-2836}, mesh = {Animals ; Base Sequence ; Chromosome Deletion ; Chromosome Mapping ; Crosses, Genetic ; Diploidy ; Drosophila melanogaster/*genetics ; Female ; *Genetic Variation ; *Introns ; Male ; Molecular Sequence Data ; *Multigene Family ; Nucleic Acid Conformation ; Oligonucleotide Probes ; RNA, Transfer, Ser/*genetics ; *Recombination, Genetic ; X Chromosome ; }, abstract = {Variant tRNA genes have been widely observed in multicellular eukaryotes. Recent biochemical studies have shown that some of them are expressed in a tissue- or a stage-specific manner. These findings would thus imply that certain modified tRNAs may be crucial for the development of the organism. Using Drosophila melanogaster as a model, we have taken a combined genetic and molecular approach to examine critically the possible biological functions of tRNA(4, 7Ser) genes. We showed that at least 50% of the total templates can be deleted from the genome without inducing abnormal phenotypes such as Minute, or a decrease in viability. In addition, two of the tRNASer variant genes that are unique in sequence are also completely dispensable. This strongly implies that even though they may be expressed in vivo, they play no essential role in the development of the fruitfly. By comparison with some of the corresponding tRNA genes in another sibling species, Drosophila erecta, our results suggest strongly that the variants are products non-reciprocal exchanges among the tRNA(4, 7Ser), genes. Such intergenic recombination events may have a major influence in the concerted evolution of the two gene families.}, } @article {pmid2018215, year = {1991}, author = {Zuckerman, RL and Wheeler, DM}, title = {Effect of halothane on arrhythmogenic responses induced by sympathomimetic agents in single rat heart cells.}, journal = {Anesthesia and analgesia}, volume = {72}, number = {5}, pages = {596-603}, doi = {10.1213/00000539-199105000-00005}, pmid = {2018215}, issn = {0003-2999}, support = {R29GM39568/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Arrhythmias, Cardiac/*chemically induced ; Culture Techniques ; Drug Interactions ; Halothane/adverse effects/*pharmacology ; Isoproterenol/adverse effects/*pharmacology ; Male ; Myocardial Contraction/*drug effects ; Norepinephrine/adverse effects/*pharmacology ; Phenylephrine/adverse effects/*pharmacology ; Rats ; Rats, Inbred Strains ; }, abstract = {The combination of catecholamines and halothane has long been recognized as arrhythmogenic. The purpose of this study was to evaluate whether the mechanism of this interaction originates at the single cell level. The incidence of spontaneous contractile waves occurring between stimulated beats (interbeat waves), early aftercontractions, and late aftercontractions was measured in rat myocytes exposed to sympathomimetics with and without halothane. Each of these endpoints in single cells has the potential to produce arrhythmias in multicellular preparations. Interbeat waves and late aftercontractions were observed with isoproterenol (1 X 10(-7) M) and norepinephrine (1-3 X 10(-7) M). The incidence of these phenomena was significantly reduced in the presence of 0.30 mM halothane. Early aftercontractions occurred in the presence of isoproterenol (1 X 10(-7) M), norepinephrine (1-3 X 10(-7) M), and phenylephrine (5-10 X 10(-6) M). There was a statistically significant decrease in the incidence of early aftercontractions in the presence of 0.30 mM halothane. These results indicate that the mechanism behind the clinically observed increased arrhythmogenicity of catecholamines with halothane does not arise at the level of single ventricular cells because halothane inhibited sympathomimetic-induced arrhythmogenic activity in this model. The probable mechanisms rather include altered impulse propagation, which might lead to phenomena such as reentry.}, } @article {pmid1868197, year = {1991}, author = {Maid, U and Zetsche, K}, title = {Structural features of the plastid ribosomal RNA operons of two red algae: Antithamnion sp. and Cyanidium caldarium.}, journal = {Plant molecular biology}, volume = {16}, number = {4}, pages = {537-546}, pmid = {1868197}, issn = {0167-4412}, mesh = {Base Sequence ; DNA, Ribosomal/*genetics ; Molecular Sequence Data ; Nucleic Acid Conformation ; *Operon ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; RNA, Ribosomal, 23S/*genetics ; RNA, Transfer, Ala/genetics ; RNA, Transfer, Ile/genetics ; Restriction Mapping ; Rhodophyta/*genetics ; Sequence Homology, Nucleic Acid ; }, abstract = {The nucleotide sequences of the plastid 16S rDNA of the multicellular red alga Antithamnion sp. and the 16S rDNA/23S rDNA intergenic spacers of the plastid DNAs of the unicellular red alga Cyanidium caldarium and of Antithamnion sp. were determined. Sequence comparisons support the idea of a polyphyletic origin of the red algal and the higher-plant chloroplasts. Both spacer regions include the unsplit tRNA(Ile)(GAU) and tRNA(Ala)(UGC) genes and so the plastids of both algae form a homogeneous group with those of chromophytic algae and Cyanophora paradoxa characterized by 'small-sized' rDNA spacers in contrast to green algae and higher plants. Nevertheless, remarkable sequence differences within the rRNA and the tRNA genes give the plastids of Cyanidium caldarium a rather isolated position.}, } @article {pmid1646800, year = {1991}, author = {Kadenbach, B and Stroh, A and Hüther, FJ and Reimann, A and Steverding, D}, title = {Evolutionary aspects of cytochrome c oxidase.}, journal = {Journal of bioenergetics and biomembranes}, volume = {23}, number = {2}, pages = {321-334}, pmid = {1646800}, issn = {0145-479X}, mesh = {Animals ; *Biological Evolution ; Cell Nucleus/metabolism ; *Electron Transport Complex IV/genetics/metabolism ; Mitochondria/metabolism ; Paracoccus denitrificans/enzymology/genetics ; Valinomycin/metabolism ; }, abstract = {The presence of additional subunits in cytochrome oxidase distinguish the multicellular eukaryotic enzyme from that of a simple unicellular bacterial enzyme. The number of these additional subunits increases with increasing evolutionary stage of the organism. Subunits I-III of the eukaryotic enzyme are related to the three bacterial subunits, and they are encoded on mitochondrial DNA. The additional subunits are nuclear encoded. Experimental evidences are presented here to indicate that the lower enzymatic activity of the mammalian enzyme is due to the presence of nuclear-coded subunits. Dissociation of some of the nuclear-coded subunits (e.g. VIa) by laurylmaltoside and anions increased the activity of the rat liver enzyme to a value similar to that of the bacterial enzyme. Further, it is shown that the intraliposomal nucleotides influence the kinetics of ferrocytochrome c oxidation by the reconstituted enzyme from bovine heart but not from P. denitrificans. The regulatory function attributed to the nuclear-coded subunits of mammalian cytochrome c oxidase is also demonstrated by the tissue-specific response of the reconstituted enzyme from bovine heart but not from bovine liver to intraliposomal ADP. These enzymes from bovine heart and liver differ in the amino acid sequences of subunits VIa, VIIa, and VIII. The results presented here are taken to indicate a regulation of cytochrome c oxidase activity by nuclear-coded subunits which act like receptors for allosteric effectors and influence the catalytic activity of the core enzyme via conformational changes.}, } @article {pmid2023134, year = {1991}, author = {Rodrigo, GC and Chapman, RA}, title = {The calcium paradox in isolated guinea-pig ventricular myocytes: effects of membrane potential and intracellular sodium.}, journal = {The Journal of physiology}, volume = {434}, number = {}, pages = {627-645}, pmid = {2023134}, issn = {0022-3751}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Biological Transport, Active/physiology ; Calcium/*metabolism ; Cell Separation/methods ; Guinea Pigs ; Male ; Membrane Potentials/physiology ; Myocardial Contraction/physiology ; Myocardium/cytology/*metabolism ; Sodium/*metabolism ; }, abstract = {1. Guinea-pig ventricular myocytes, isolated enzymatically without the aid of special media, show a similar sensitivity to the calcium paradox as Langendorff-perfused hearts. 2. Measurement of the intracellular activities of Na+ and Ca2+ ions, with a suction-type ion-sensitive microelectrode at rest, during calcium depletion and during inhibition of the Na+ pump (under both current and voltage clamp) yield values similar to those obtained from multicellular preparations and from isolated myocytes by other means. 3. In voltage-clamped myocytes bathed by media free of divalent cations, an inward sodium current that flows through the L-type Ca2+ channels, the rate of rise of aiNa and the strength of the contraction induced by return to normal Tyrode solution, show a similar bell-shaped dependence on the membrane potential during the period of Ca2+ deprivation. 4. The rise in aiNa that occurs in Ca(2+)-free, Mg(2+)-free media, induces an outward current which is composed of currents due to activation of the Na+ pump and K+ channels. 5. On Ca2+ repletion the loading of the cells with Ca2+ does not generate an inward current and the contracture can be reduced, in a dose-dependent way, by the introduction of BAPTA into the sarcoplasm from the solution in the voltage electrode. When [Ca2+]i is buffered by added BAPTA, the estimated amount of Ca2+ which can enter on Ca2+ repletion is sufficient to bind up to 10 mM of the BAPTA. This change in concentration is similar to that expected from the rise and fall in aiNa, seen on Ca2+ depletion and repletion, if a 3 Na+:1 Ca2+ exchange is responsible for the Ca2+ influx. 6. These data offer support for the so-called intracellular sodium hypothesis for the origin of the calcium paradox in the heart. As the effects of Ca2+ repletion can be prevented by clamping the membrane potential so that aiNa does not rise, the contribution of the other effects of Ca2+ depletion to the initiation of the calcium paradox would seem to be less important.}, } @article {pmid1847744, year = {1991}, author = {Kamiya, K and Gould, MN and Clifton, KH}, title = {Differential control of alveolar and ductal development in grafts of monodispersed rat mammary epithelium.}, journal = {Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)}, volume = {196}, number = {3}, pages = {284-292}, doi = {10.3181/00379727-196-43190}, pmid = {1847744}, issn = {0037-9727}, support = {P30 CA14520/CA/NCI NIH HHS/United States ; R37 CA13881/CA/NCI NIH HHS/United States ; }, mesh = {Adrenal Glands/physiology ; Adrenalectomy ; Adrenocorticotropic Hormone/physiology ; Animals ; Cell Differentiation/physiology ; Epithelial Cells ; Epithelium/transplantation ; Female ; Hydrocortisone/physiology ; Mammary Glands, Animal/*growth & development ; Mammary Neoplasms, Animal/metabolism ; Microscopy, Electron ; Prolactin/physiology ; Rats ; Rats, Inbred F344 ; Rats, Inbred WF ; Tumor Stem Cell Assay ; }, abstract = {Multicellular secretory alveolar units (AU) develop in grafts of monodispersed mammary cells in intact recipient rats co-grafted with mammotropic hormone-secreting pituitary tumor (MtT). The cumulative evidence is consistent with a postulated clonal origin of these structures. Small numbers of multicellular structures of a second type, mammary ductal units (DU), were found in mammary cell grafts in intact Wistar/Furth recipients co-grafted with MtT W10 but not in intact F344 recipients co-grafted with MtT F4. Studies in (Wistar/Furth x F344) F1 hybrid recipients grafted with mammary cells from either parent strain demonstrated that this difference in DU formation is dependent on the strain of grafted MtT, and is not a genetic characteristic of the rat strain. DU formation is stimulated and AU formation is inhibited by elevation of mammotropic hormones from MtT coupled with glucocorticoid deficiency induced by adrenalectomy. cortisol treatment reverses this effect. Finally, in mammary glands in situ in intact rats, the total numbers of AU-forming clonogens decrease during 6 weeks after MtT transplantation. In contrast, during the same period, elevated mammotropins from grafted MtT coupled with glucocorticoid deficiency from adrenalectomy cause an increase in the total number of cells that are capable of AU formation when transplanted to intact recipients co-grafted with MtT. Thus, the same hormonal combination that stimulates DU formation in mammary cell grafts and has previously been shown to promote cancer in mammary glands in situ also stimulates an increase in the glandular content of assayable AU-forming cells in situ.}, } @article {pmid1988137, year = {1991}, author = {Mertens, F and Heim, S and Mandahl, N and Johansson, B and Mertens, O and Persson, B and Salemark, L and Wennerberg, J and Jonsson, N and Mitelman, F}, title = {Cytogenetic analysis of 33 basal cell carcinomas.}, journal = {Cancer research}, volume = {51}, number = {3}, pages = {954-957}, pmid = {1988137}, issn = {0008-5472}, mesh = {Aged ; Carcinoma, Basal Cell/*genetics ; Chromosome Aberrations/genetics ; Female ; Humans ; Karyotyping ; Male ; Middle Aged ; Skin Neoplasms/*genetics ; }, abstract = {Cytogenetic analysis of short-term cultures from 33 basal cell carcinomas (BCC), a type of neoplasm for which no previous karyological data exist, revealed clonal chromosome aberrations, all of them different, in 8 tumors. In 2 cases, 2 cytogenetically unrelated clones were detected, suggesting a multicellular origin in at least a subset of BCC. A remarkably high level of nonclonal structural rearrangements, mostly in the form of seemingly balanced translocations, was found in 23 tumors; namely, in 6 of 8 BCC with clonal karyotypic abnormalities and in 17 of 25 without. It is possible that some of these aberrations represent additional neoplastic clones, thus indicating an even higher level of cytogenetic heterogeneity in BCC. We think that the most likely interpretation of the results is that BCC may have a multicellular origin, reflecting field cancerization of the skin. During subsequent tumor development, the selection pressure narrows down the number of clones that infiltrate the surrounding tissue. The finding by karyotypic analysis of some apparently monoclonal, some polyclonal BCC, may reflect that different tumors have been examined at different points in the clonal evolution of the neoplastic cells.}, } @article {pmid1858129, year = {1991}, author = {Lake, JA}, title = {Tracing origins with molecular sequences: metazoan and eukaryotic beginnings.}, journal = {Trends in biochemical sciences}, volume = {16}, number = {2}, pages = {46-50}, doi = {10.1016/0968-0004(91)90020-v}, pmid = {1858129}, issn = {0968-0004}, mesh = {Animals ; *Base Sequence ; *Biological Evolution ; Eukaryotic Cells ; Molecular Sequence Data ; Phylogeny ; RNA, Ribosomal/genetics ; Sequence Homology, Nucleic Acid ; }, abstract = {Milestones in the evolution of the eukaryotic cell are being discovered through the analysis of molecular sequences. As sequence data become increasingly plentiful, our ability to reconstruct the most distant evolutionary branchings of evolutionary trees is limited only by the mathematics of phylogenetic reconstruction. Analysis of ribosomal RNAs agrees with traditional analyses of morphological and developmental characters that all multicellular animals probably arose from a common ancestor, but highlights one of the major limitations of the various mathematical algorithms used. Refined methods of sequence analysis also suggest a previously unsuspected sister relationship between the eukaryotic nucleus and eocytes, a group of extremely thermophilic, sulfur-metabolizing bacteria, that questions the classical eukaryote/prokaryote division.}, } @article {pmid1936050, year = {1991}, author = {Feinendegen, LE}, title = {Radiation risk of tissue late effects, a net consequence of probabilities of various cellular responses.}, journal = {European journal of nuclear medicine}, volume = {18}, number = {9}, pages = {740-751}, pmid = {1936050}, issn = {0340-6997}, mesh = {Cell Survival/radiation effects ; DNA/radiation effects ; DNA Repair ; Dose-Response Relationship, Radiation ; Humans ; Neoplasms, Radiation-Induced/*epidemiology ; *Neoplasms, Second Primary ; Occupational Diseases/*epidemiology ; Radiation Injuries/*epidemiology ; Risk Factors ; Time Factors ; }, abstract = {Late effects from the exposure to low doses of ionizing radiation are hardly or not at all observed in man probably due to the low values of risk coefficients that preclude statistical analyses of data from populations that are exposed to doses less than 0.2 Gy. In order to arrive at an assessment of potential risk from radiation exposure in the low dose range, the microdosimetry approach is essential. In the low dose range, ionizing radiation generates particle tracks, mainly electrons, which are distributed rather heterogenously within the exposed tissue. Taking the individual cell as the elemental unit of life, observations and calculations of cellular responses to being hit by energy deposition events from low LET type are analysed. It emerges that besides the probability of a hit cell to sustain a detrimental effect with the consequence of malignant transformation there are probabilities of various adaptive responses that equip the hit cell with a benefit. On the one hand, an improvement of cellular radical detoxification was observed in mouse bone marrow cells; another adaptive response pertaining to improved DNA repair, was reported for human lymphocytes. The improved radical detoxification in mouse bone marrow cells lasts for a period of 5-10 hours and improved DNA repair in human lymphocytes was seen for some 60 hours following acute irradiation. It is speculated that improved radical detoxification and improved DNA repair may reduce the probability of spontaneous carcinogenesis. Thus it is proposed to weigh the probability of detriment for a hit cell within a multicellular system against the probability of benefit through adaptive responses in other hit cells in the same system per radiation exposure. In doing this, the net effect of low doses of low LET radiation in tissue with individual cells being hit by energy deposition events could be zero or even beneficial. Since there was no simple additivity of equal effects from repeated exposures to equal doses and because of the potential effect of adaptive cell responses on the spontaneous evolution of malignancy in tissue, the extrapolation of risk with absorbed dose reaching down to zero, does not appear to be generally valid.}, } @article {pmid1871510, year = {1991}, author = {Schwachöfer, JH and Crooijmans, RP and Hoogenhout, J and Kal, HB and Theeuwes, AG}, title = {Sublethal damage repair in two radioresistant human tumor cell lines irradiated as multicellular spheroids.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {12}, number = {4}, pages = {207-216}, doi = {10.1159/000217706}, pmid = {1871510}, issn = {1010-4283}, mesh = {Adenocarcinoma/radiotherapy ; Cell Division/radiation effects ; Cell Survival/radiation effects ; Dose-Response Relationship, Radiation ; Humans ; Lung Neoplasms/radiotherapy ; Melanoma/radiotherapy ; Radiation Dosage ; *Radiation Tolerance ; Skin Neoplasms/radiotherapy ; Tumor Cells, Cultured/*radiation effects ; }, abstract = {Melanoma and lung adenocarcinoma may be amenable for radiotherapy if it were possible to increase the presently used total dose. In order to investigate this, spheroids from two cell lines of human origin, one obtained from a BRO melanoma and one from an NCI-H125 lung adenocarcinoma were exposed to graded doses (3-9 Gy) of radiation with 18-MV photons. Radiation was applied either as a single dose or as split doses with an interval of 6 h to determine the extent of sublethal damage repair. Radiation response was quantified in terms of spheroid cure and specific growth delay. Both cells lines have previously been shown to be less sensitive than a neuroblastoma and a squamous cell carcinoma cell line grown as spheroids. Data obtained from the growth delay analysis were used to calculate the extent of split-dose recovery. Repaired dose for BRO spheroids did not increase after 7 Gy, whereas in NCI-H125, the repaired dose showed a steady increase. Recovery ratios did not differ between the two cell lines, but were lower than reported for normal tissues. Both cell lines revealed a low repair capacity was expressed by the beta-value of the linear-quadratic (LQ) equation. However, repair capacity for sublethal damage as expressed by the dose repaired and the beta-value of the LQ equation was not different from values reported earlier by us for neuroblastoma and squamous cell carcinoma when grown as spheroids. This indicates that the low radiosensitivity for the cell lines used in this study is determined by the alpha-value of the LQ equation. Our results support the clinical finding that the application of increased total radiation doses in the treatment of melanoma and lung adenocarcinoma may be feasible if radiation is applied in multiple small fractions to ensure normal tissue sparing.}, } @article {pmid1752167, year = {1991}, author = {Lewis, J}, title = {Rules for the production of sensory cells.}, journal = {Ciba Foundation symposium}, volume = {160}, number = {}, pages = {25-39; discussion 40-53}, pmid = {1752167}, issn = {0300-5208}, mesh = {Animals ; Ear, Inner/cytology ; Mechanoreceptors/cytology ; Nerve Regeneration ; Nervous System/*cytology/growth & development ; Nervous System Physiological Phenomena ; Retina/cytology ; Sensory Receptor Cells/*anatomy & histology/growth & development/physiology ; }, abstract = {During development and regeneration, cells divide, move, change their internal state, respond to environmental signals and die according to rules specified by their genome. These rules of cell behaviour are fundamental to any explanation of how sensory tissues are generated or repaired. An attempt is made to summarize and compare the rules underlying the development of four different sensory tissues: mammalian retina, avian auditory epithelium, mechanosensory bristle fields in Drosophila and, very briefly, Drosophila retina. There are parallels in cell lineage, in the timing of developmental decisions, in the postponement of the choice of differentiated state until the final cell division cycle, in the role of short-range lateral inhibition, and in the involvement of genes such as Notch and achaete/scute. These similarities may reflect the conservation of some basic mechanisms of sensory development that originated early in the evolution of multicellular animals. If so, studies in Drosophila, with its advantages for molecular genetics, may give important clues to the mechanisms of sensory development and regeneration in vertebrates.}, } @article {pmid1685369, year = {1991}, author = {Pertseva, M}, title = {The evolution of hormonal signalling systems.}, journal = {Comparative biochemistry and physiology. A, Comparative physiology}, volume = {100}, number = {4}, pages = {775-787}, doi = {10.1016/0300-9629(91)90292-k}, pmid = {1685369}, issn = {0300-9629}, mesh = {Animals ; *Biological Evolution ; Eukaryotic Cells/physiology ; Hormones/*physiology ; Invertebrates/physiology ; Receptors, Cell Surface/physiology ; Signal Transduction/*physiology ; Vertebrates/physiology ; }, abstract = {1. A comparative analysis was made of chemosignalling systems responsible for the action of hormones, hormone-like substances, pheromones, etc. in vertebrates--multicellular invertebrates--unicellular eukaryotes. Many common features revealed in structural-functional organization of the above systems give evidence of their evolutionary conservatism. 2. It was shown that some molecular components as well as signal transduction mechanisms similar to those of higher eukaryote hormonal signalling systems are present in such early organisms as bacteria. This allowed a suggestion that the roots of chemosignalling systems are likely to be found in prokaryotes. 3. The evolution of hormonal signalling systems is discussed in terms of current theories of the origin of eukaryotic cell, its organelles and components. A hypothesis is put forward about endosymbiotic genesis of these signal transduction systems in eukaryotes. 4. A possible evolutionary scenario of the formation of hormonocompetent systems is proposed with hormone-sensitive adenylate cyclase complex taken as an example.}, } @article {pmid1668372, year = {1991}, author = {Larsson, L and Timms, E and Blight, K and Restall, DE and Jat, PS and Fisher, AG}, title = {Characterization of murine thymic stromal-cell lines immortalized by temperature-sensitive simian virus 40 large T or adenovirus 5 E1a.}, journal = {Developmental immunology}, volume = {1}, number = {4}, pages = {279-293}, doi = {10.1155/1991/14636}, pmid = {1668372}, issn = {1044-6672}, mesh = {Adenovirus Early Proteins ; Adenoviruses, Human/genetics/*physiology ; Animals ; Antigens, Polyomavirus Transforming/biosynthesis/genetics/*physiology ; Cell Line, Transformed ; *Cell Transformation, Viral ; Genetic Vectors ; H-2 Antigens/biosynthesis/immunology ; Mice ; Mice, Inbred AKR ; Mice, Inbred BALB C ; Oncogene Proteins, Viral/genetics/*physiology ; Retroviridae ; Simian virus 40/genetics/*physiology ; Temperature ; Thymus Gland/*cytology ; Vimentin/biosynthesis ; }, abstract = {The heterogeneity of thymic stromal cells is probably related to their role in providing different microenvironments where T cells can develop. We have immortalized thymic stromal elements using recombinant retroviral constructs containing a temperature-sensitive simian virus 40 (SV40tsA58) large-T antigen gene or the adenovirus 5 E1a region linked to the gene coding for resistance to G418. Cell lines containing the thermolabile large T antigen encoded by SV40 proliferate at the permissive temperature of 33 degrees C and arrest growth when transferred to the nonpermissive temperature of 39 degrees C. At the nonpermissive temperature, ts-derived cell lines are shown to alter their phenotype but remain metabolically active, as indicated by the inducible expression of class I and class II MHC antigens. Here we describe the generation of a total of 84 thymic stromal-cell lines, many of which show distinct morphologic, phenotypic, and functional properties consistent with fibroblastoid, epithelial, or monocytoid origins. Several E1a and SV40tsA58-derived cell lines generated exhibit the epithelial characteristic of desmosome formation and, in addition, two of these lines (15.5 and 15.18) form multicellular complexes (rosettes) when incubated with unfractionated thymocytes from syngeneic mice. A single line (14.5) displays very strong nonspecific esterase activity, suggesting it may represent a macrophagelike cell type. We describe the generation of stromal cell lines with different properties, which is consistent with the heterogeneity found in the thymic microenvironment. In addition to documenting this diversity, these cell lines may be useful tools for studying T-cell development in vitro and give access to model systems in which stromal-thymocyte interactions can be examined.}, } @article {pmid2123549, year = {1990}, author = {Strathmann, M and Simon, MI}, title = {G protein diversity: a distinct class of alpha subunits is present in vertebrates and invertebrates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {87}, number = {23}, pages = {9113-9117}, pmid = {2123549}, issn = {0027-8424}, support = {GM34236/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Biological Evolution ; Drosophila/genetics ; GTP-Binding Proteins/*genetics ; *Genetic Variation ; Invertebrates/*genetics ; Macromolecular Substances ; Molecular Sequence Data ; *Multigene Family ; Oligonucleotide Probes ; Polymerase Chain Reaction ; Sequence Homology, Nucleic Acid ; Vertebrates/*genetics ; }, abstract = {Heterotrimeric guanine nucleotide-binding proteins (G proteins) are integral to the signal transduction pathways that mediate the cell's response to many hormones, neuromodulators, and a variety of other ligands. While many signaling processes are guanine nucleotide dependent, the precise coupling between a variety of receptors, G proteins, and effectors remains obscure. We found that the family of genes that encode the alpha subunits of heterotrimeric G proteins is much larger than had previously been supposed. These novel alpha subunits could account for some of the diverse activities attributed to G proteins. We have now obtained cDNA clones encoding two murine alpha subunits, G alpha q and G alpha 11, that are 88% identical. They lack the site that is ordinarily modified by pertussis toxin and their sequences vary from the canonical Gly-Ala-Gly-Glu-Ser (GAGES) amino acid sequence found in most other G protein alpha subunits. Multiple mRNAs as large as 7.5 kilobases hybridize to G alpha q specific probes and are expressed at various levels in many different tissues. G alpha 11 is encoded by a single 4.0-kilobase message which is expressed ubiquitously. Amino acid sequence comparisons suggest that G alpha q and G alpha 11 represent a third class of alpha subunits. A member of this class was found in Drosophila melanogaster. This alpha subunit, DG alpha q, is 76% identical to G alpha q. The presence of the Gq class in both vertebrates and invertebrates points to a role that is central to signal transduction in multicellular organisms. We suggest that these alpha subunits may be involved in pertussis toxin-insensitive pathways coupled to phospholipase C.}, } @article {pmid2078870, year = {1990}, author = {Kostrzewa, M and Valentin, K and Maid, U and Radetzky, R and Zetsche, K}, title = {Structure of the rubisco operon from the multicellular red alga Antithamnion spec.}, journal = {Current genetics}, volume = {18}, number = {5}, pages = {465-469}, pmid = {2078870}, issn = {0172-8083}, mesh = {Amino Acid Sequence ; Base Sequence ; Genes ; Molecular Sequence Data ; *Operon ; Rhodophyta/*genetics ; Ribulose-Bisphosphate Carboxylase/*genetics ; Sequence Homology, Nucleic Acid ; Transcription, Genetic ; }, abstract = {In the multicellular red alga Antithamnion spec. both rubisco genes (rbcL and rbcS) are encoded on the plastid DNA (ptDNA). Both genes are separated by a short A/T-rich spacer of 100 bp and are cotranscribed into an mRNA of approximately 2.7 kb. These findings are in extensive agreement with those obtained from two unicellular red algae (Porphyridium aerugineum and Cyanidium caldarium). The large subunit (LSU) of rubisco shows an amino acid homology of 82-87% with the LSUs from the two unicellular red algae and only about 55% to LSUs from green algae, higher plants and two cyanobacteria. The small subunit (SSU) of rubisco is more similar to those from the unicellular red algae and two algae which are members of the Chromophyta (about 60% homology) than to cyanobacterial and higher plant proteins (27-36% homology). These data indicate that rhodoplasts originated independently from the chloroplast line. The plastids of chromophytes and rhodophytes appear to be closely related.}, } @article {pmid1708086, year = {1990}, author = {Shimkets, LJ}, title = {Social and developmental biology of the myxobacteria.}, journal = {Microbiological reviews}, volume = {54}, number = {4}, pages = {473-501}, pmid = {1708086}, issn = {0146-0749}, mesh = {Base Sequence ; Biological Evolution ; DNA, Bacterial/*chemistry ; Molecular Sequence Data ; Myxococcales/classification/genetics/growth & development/*physiology ; Nucleic Acid Conformation ; RNA, Bacterial/*chemistry ; }, abstract = {Myxobacteria are soil bacteria whose unusually social behavior distinguishes them from other groups of procaryotes. Perhaps the most remarkable aspect of their social behavior occurs during development, when tens of thousands of cells aggregate and form a colorful fruiting body. Inside the fruiting body the vegetative cells convert into dormant, resistant myxospores. However, myxobacterial social behavior is not restricted to the developmental cycle, and three other social behaviors have been described. Vegetative cells have a multigene social motility system in which cell-cell contact is essential for gliding in multicellular swarms. Cell growth on protein is cooperative in that the growth rate increases with the cell density. Rippling is a periodic behavior in which the cells align themselves in ridges and move in waves. These social behaviors indicate that myxobacterial colonies are not merely collections of individual cells but are societies in which cell behavior is synchronized by cell-cell interactions. The molecular basis of these social behaviors is becoming clear through the use of a combination of behavioral, biochemical, and genetic experimental approaches.}, } @article {pmid11538072, year = {1990}, author = {Butterfield, NJ and Knoll, AH and Swett, K}, title = {A bangiophyte red alga from the Proterozoic of arctic Canada.}, journal = {Science (New York, N.Y.)}, volume = {250}, number = {}, pages = {104-107}, doi = {10.1126/science.11538072}, pmid = {11538072}, issn = {0036-8075}, mesh = {*Biological Evolution ; Canada ; *Fossils ; Geological Phenomena ; Geology ; Paleontology ; Rhodophyta/*classification/cytology ; }, abstract = {Silicified peritidal carbonate rocks of the 1250- to 750-million-year-old Hunting Formation, Somerset Island, arctic Canada, contain fossils of well-preserved bangiophyte red algae. Morphological details, especially the presence of multiseriate filaments composed of radially arranged wedge-shaped cells derived by longitudinal divisions from disc-shaped cells in uniseriate filaments, indicate that the fossils are related to extant species in the genus Bangia. Such taxonomic resolution distinguishes these fossils from other pre-Ediacaran eukaryotes and contributes to growing evidence that multicellular algae diversified well before the Ediacaran radiation of large animals.}, } @article {pmid2383882, year = {1990}, author = {Toussaint-Demylle, D and Scheiff, JM and Haumont, S}, title = {Thymic nurse cells: morphological study during their isolation from murine thymus.}, journal = {Cell and tissue research}, volume = {261}, number = {1}, pages = {115-123}, pmid = {2383882}, issn = {0302-766X}, mesh = {Animals ; Cell Communication/physiology ; Cell Separation/methods ; Epithelial Cells ; Epithelium/physiology/ultrastructure ; Female ; Mice ; Microscopy, Electron ; Thymus Gland/*cytology/physiology/ultrastructure ; }, abstract = {Thymic nurse cells (TNC), which are multicellular complexes composed of epithelial cells and thymocytes, were obtained from C3H-mice thymuses. They were described by means of light and electron microscopy. The morphology of epithelial cells forming isolated TNC compared to that of small tissue fragments obtained by enzymatic digestion revealed that TNC could be derived from all parts of the thymus: cortex, corticomedullary junction and medulla, the cortex being their principal source. This variety of origin, the presence of several epithelial cells inside a single TNC, the presence of non-lymphoid cells, and the various locations of cleaved desmosomes confirmed that their aspect "in vitro" as round and sealed structures can be considered to be an artifact due to the isolation technique used. Indeed, during this procedure, they are formed by a process of wrapping of the epithelial cytoplasm around the tightly associated thymocytes. All three epithelial cell types: cortical reticular cells, medullary reticular cells, and medullary globular cells can form TNC.}, } @article {pmid2376781, year = {1990}, author = {Leber, SM and Breedlove, SM and Sanes, JR}, title = {Lineage, arrangement, and death of clonally related motoneurons in chick spinal cord.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {10}, number = {7}, pages = {2451-2462}, doi = {10.1523/JNEUROSCI.10-07-02451.1990}, pmid = {2376781}, issn = {0270-6474}, support = {T32 NS07027/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Cell Survival ; Chick Embryo ; Clone Cells ; Interneurons/cytology ; Motor Neurons/*cytology/physiology ; Neurons/cytology ; Spinal Cord/anatomy & histology/*cytology/embryology ; }, abstract = {We have used recombinant retroviruses as lineage markers to study the genealogy of motoneurons (MNs) in the chick spinal cord. We infected individual progenitors by injecting virions into the neural tube at stages 11-18, a few cell divisions before MNs are born. The descendants of infected cells were subsequently detected with a histochemical stain for beta-galactosidase (lacZ), the product of the retrovirally introduced gene. Clonally related, lacZ-positive cells formed clusters that were usually radial or planar in shape. The cells that comprised these clones were classified by morphology, size, and location. About 15% of the clones in the spinal cord contained MNs, and these were studied further. Multicellular clones that contained only MNs were infrequent. Instead, close relatives of MNs included a variety of other neurons, as well as glia and ependymal cells. Most non-MNs in these clones were found in the ventral and intermediate parts of the spinal cord. Neurons included interneurons and autonomic preganglionic neurons in the column of Terni. Labeled glia were found in both the gray and white matter and included astrocytes and cells tentatively identified as oligodendrocytes. Thus, even shortly before MNs are born, their progenitors are multipotential. Clonally related MNs were not restricted to a single motor pool. Some clones contained MNs in both the medial and lateral parts of the lateral motor column, which are known to innervate distinct groups of limb muscles. Furthermore, some clones contained MNs in the medial motor column (which innervate axial muscles) as well as in the lateral motor column. In contrast, the dispersal of clonally related MNs (and other neurons) was restricted in the rostrocaudal axis; most clones were less than one-quarter segment in length. Thus, MNs derived from a single progenitor are more likely to share rostrocaudal position than synaptic targets. To investigate the fate of clonally related MNs, we counted the number of MNs per clone at times before, during, and after the major period of MN death. The number of MNs per clone declined in precise parallel with the total number of MNs during this period, suggesting that neurons are eliminated without regard to their clone of origin. This result implies that the decision to live or die occurs on a cell-by-cell rather than a clone-by-clone basis.}, } @article {pmid2200335, year = {1990}, author = {Schwachöfer, JH}, title = {Multicellular tumor spheroids in radiotherapy research (review).}, journal = {Anticancer research}, volume = {10}, number = {4}, pages = {963-969}, pmid = {2200335}, issn = {0250-7005}, mesh = {Animals ; Cell Survival/radiation effects ; Humans ; Neoplasms/pathology/radiotherapy ; Radiation Tolerance ; Tumor Cells, Cultured/*radiation effects ; Tumor Stem Cell Assay ; }, abstract = {Culturing of human tumor cells as multicellular spheroids can be a tool to study radiation responses. The degree of structural and functional differentiation in the primary tumor may be retained in spheroids rather than in conventional monolayer cultures. In the liquid overlay culture technique spheroids can be individually assessed for their responses to treatment, whereas in spinner flasks, large quantities of similarly sized spheroids can be produced. Studying the response of spheroids to irradiation can be performed on single cells obtained after disaggregation of these spheroids, or on intact spheroids, using cure and growth delay as endpoints. Clonogenic cell survival is especially difficult to perform on spheroids of human tumor cells. Modern calculation methods, however, may offer promising correlates between growth curves and single cell survival. Spheroids of human tumor cell lines show tumor type dependent radiation responses, offering an approach for comparison of radiosensitivity of tumor cell lines of different histologic origin. Contact effect, as a modifying factor of radiation response in spheroids, has especially been studied in murine cell lines. The use however, of human tumor cell lines, may offer new insight in this phenomenon. Radiobiologic hypoxia has been observed in spheroids of both murine and human origin. Reoxygenation after irradiation has also been described by radiobiologic parameters. So far, no physiologic reoxygenation processes after radiation treatment have been identified. In view of the clinical relevance of oxygen to radiation responses and treatment outcome, reoxygenation processes should be further elucidated in spheroids of human origin. Repair of potentially lethal damage in spheroids has been reported for only one murine cell line. In an indirect manner it has also been studied in spheroids of human origin. Sublethal damage repair has been studied rather extensively in murine cell line spheroids. However, only recently it has been reported in human tumor spheroids in relation to the clinical curability of the tumors of origin. Use of human tumor cell lines to study radiation responses of spheroids is necessary to determine tumor type dependent differences in several radiation related phenomena, such as reoxygenation, contact effect, and repair processes.}, } @article {pmid2402151, year = {1990}, author = {Hurst, LD}, title = {Parasite diversity and the evolution of diploidy, multicellularity and anisogamy.}, journal = {Journal of theoretical biology}, volume = {144}, number = {4}, pages = {429-443}, doi = {10.1016/s0022-5193(05)80085-2}, pmid = {2402151}, issn = {0022-5193}, mesh = {Animals ; *Biological Evolution ; Diploidy ; Genetic Variation/*genetics ; Host-Parasite Interactions/*genetics ; Male ; Mitosis ; Parasites/*genetics ; Spermatozoa/cytology ; }, abstract = {It may be reasonably assumed that a diversity of parasite genotypes in any one cell or organism is more harmful than a population of uniform genotypes. If this is accepted the following consequences follow: (i) Parasite mixing, due to cytoplasm mixing, at the time of zygote formation is a new and additional cost of sex. The rapid divisions typical of zygotic cleavage may be viewed as an adaptation to minimize the degree of mixing of parasites in each daughter cell. The faster the divisions the less chance parasite populations have to grow and mix. Mitosis is the fastest form of cell division. Prolongation of the diploid phase follows as a consequence of mitosis in a diploid zygote. This view is unusual in that it demands no advantage per se to the possession of two chromosome sets. (ii) The cells of the blastula formed from rapid zygotic divisions are different as regards their symbiotic inclusions. If the right to gametogenesis is restricted, then every replicator symbiont and nuclear genome alike and hence every cell of the developing embryo, will have an incentive to compete. Selection between the clonal blastula cells would result in the cells of low parasite diversity forming the gametes. Thus, germ line restriction is in the interests of the nuclear genome. Controlling the right to gametogenesis is only possible if the blastula remains intact. Hence, multicellularity might have evolved so as to enable the limitation of the right to gametogenesis and hence reduce the parasite diversity of gametes. Inter-cell competition during embryogenesis is central to Buss's seminal notion of the evolution of developmental complexity within the metazoa. The above theory provides the missing motive force behind such competition. (iii) For a given zygote size, the fittest zygotes are those produced by the gametes most disparate in size because these have a lower diversity of parasites. This may be the advantage of anisogamy. The novelty of this new view of anisogamy is that it puts a premium on sperm being very small, in order to exclude parasites from sperm cytoplasm. The hypothesis is briefly tested by examining if there are alternative means of parasite limitation in organisms with large gametes.}, } @article {pmid2112608, year = {1990}, author = {Lees-Miller, JP and Yan, A and Helfman, DM}, title = {Structure and complete nucleotide sequence of the gene encoding rat fibroblast tropomyosin 4.}, journal = {Journal of molecular biology}, volume = {213}, number = {3}, pages = {399-405}, doi = {10.1016/S0022-2836(05)80202-5}, pmid = {2112608}, issn = {0022-2836}, support = {CA46370/CA/NCI NIH HHS/United States ; GM43049/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Biological Evolution ; Cells, Cultured ; DNA/analysis ; Drosophila melanogaster/genetics ; Exons ; Fibroblasts/*metabolism ; Humans ; Molecular Sequence Data ; RNA Splicing ; RNA, Messenger/biosynthesis ; Rats ; Repetitive Sequences, Nucleic Acid ; Tropomyosin/biosynthesis/*genetics ; }, abstract = {We have isolated and determined the complete nucleotide sequence of the gene that encodes the 248 amino acid residue fibroblast tropomyosin, TM-4. The TM-4 sequence is encoded by eight exons, which span approximately 16,000 bases. The position of the intron-exon splice junctions relative to the final transcript are identical to those present in other vertebrate tropomyosin genes and the Drosophila melanogaster TMII gene. We have found no evidence that the rat TM-4 gene is alternatively spliced, unlike all the other tropomyosin genes from multicellular organisms that have been described. Typical vertebrate tropomyosin genes contain some, or all, of alternatively spliced exons 1a and 1b, 2a and 2b, 6a and 6b, and 9a, 9b, 9c and 9d in addition to common exons 3, 4, 5, 7 and 8. The rat fibroblast TM-4 mRNA is encoded by sequences most similar to exons 1b, 3, 4, 5, 6b, 7, 8 and 9d. Two exon-like sequences that are highly similar to alternatively spliced exons 2b and 9a of the rat beta-tropomyosin gene and the human TMnm gene have been located in the appropriate region of the gene encoding rat fibroblast TM-4. However, several mutations in these sequences render them non-functional as tropomyosin coding exons. We have termed these exon-like sequences, vestigial exons. The evolutionary relationship of the rat TM-4 gene relative to other vertebrate tropomyosin genes is discussed.}, } @article {pmid2149647, year = {1990}, author = {Pines, J and Hunter, T}, title = {p34cdc2: the S and M kinase?.}, journal = {The New biologist}, volume = {2}, number = {5}, pages = {389-401}, pmid = {2149647}, issn = {1043-4674}, mesh = {Amino Acid Sequence ; Animals ; CDC2 Protein Kinase/*metabolism ; Cyclins/pharmacology ; Humans ; *Mitosis ; Molecular Sequence Data ; Phosphorylation/drug effects ; *S Phase ; Substrate Specificity ; }, abstract = {In the yeast cell cycle, the induction of two very different processes, DNA synthesis (S-phase) and mitosis (M-phase), requires the same serine/threonine-specific protein kinase p34cdc2, which has been highly conserved through evolution. On the basis of work conducted largely in multicellular eukaryotes, it has recently been suggested that p34cdc2 is able to perform these two mutually exclusive roles by phosphorylating different sets of substrates through a cell cycle-dependent association with other proteins that dictate the substrate specificity of the protein kinase. To recognize its mitotic substrates, p34cdc2 associates with one of the cyclins--a family of proteins of two distinct but related types (A and B) characterized by their periodic destruction at each mitosis. In interphase, the formation of a complex between p34cdc2 and another protein (or proteins) would allow the phosphorylation of a different set of proteins involved in the G1 to S transition. This review focuses on the evidence for this appealing simple model and the nature of the putative substrates proposed.}, } @article {pmid2297813, year = {1990}, author = {Kimura, S and Bassett, AL and Furukawa, T and Cuevas, J and Myerburg, RJ}, title = {Electrophysiological properties and responses to simulated ischemia in cat ventricular myocytes of endocardial and epicardial origin.}, journal = {Circulation research}, volume = {66}, number = {2}, pages = {469-477}, doi = {10.1161/01.res.66.2.469}, pmid = {2297813}, issn = {0009-7330}, support = {HL-21735/HL/NHLBI NIH HHS/United States ; LH-19044//PHS HHS/United States ; }, mesh = {Action Potentials/drug effects ; Animals ; Cats ; Coronary Disease/*physiopathology ; Electrophysiology ; Endocardium/pathology/*physiopathology ; Heart Ventricles ; Lysophosphatidylcholines/pharmacology ; Pericardium/pathology/*physiopathology ; }, abstract = {In multicellular preparations, there are differences in action potential configuration between endocardium and epicardium, and electrophysiological alterations induced by ischemia are more drastic in epicardium than in endocardium. The present study was designed to examine electrophysiological properties of single cardiac myocytes enzymatically isolated from the endocardial and epicardial surfaces of the cat left ventricle and to determine whether the differential responses to ischemia of intact tissue occur in single cells. Action potentials recorded from the isolated single cells of epicardial surface had lower action potential amplitude and a prominent notch between phase 1 and phase 2, compared with those of the cells isolated from the endocardial surface; these findings are similar to those in intact endocardial and epicardial preparations. Resting membrane potentials recorded from both endocardial and epicardial single cells were sensitive to the change in extracellular K+ concentration and had properties of a K+ electrode. Action potential duration was frequency dependent in both cell types and was shorter in epicardial cells than in endocardial cells at a stimulation rate of 3 Hz. When the cells were superfused with Tyrode's solution that was altered to mimic an ischemic environment in vivo (PO2, 30-40 mm Hg; pH 6.8; [K+], 10 mM; and glucose free), resting membrane potential, action potential amplitude, and action potential duration were reduced, and the refractory period was shortened in both endocardial and epicardial single cells, but there were no differences in the degree of changes in action potentials and refractory periods induced between the two cell types. Action potential changes induced by L-alpha-lysophosphatidylcholine (5-40 mg/l) were also similar in endocardial and epicardial single cells.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid11538690, year = {1990}, author = {Grant, SW}, title = {Shell structure and distribution of Cloudina, a potential index fossil for the terminal Proterozoic.}, journal = {American journal of science}, volume = {290-A}, number = {}, pages = {261-294}, pmid = {11538690}, issn = {0002-9599}, mesh = {Animals ; *Biological Evolution ; Brazil ; *Calcium Carbonate ; California ; China ; *Classification ; Earth, Planet ; *Fossils ; Geological Phenomena ; Geology ; Mexico ; Namibia ; Nevada ; *Paleontology ; Spain ; }, abstract = {Cloudina-bearing biosparites and biomicrites in the lower part of the Nama Group, Namibia, contain a wide morphological diversity of shell fragments that can all be attributed to the two named species C. hartmannae and C. riemkeae. The curved to sinuous tubular shells of Cloudina were multi-layered. Each shell layer was 8 to 50 micrometers thick and in the form of a slightly flaring tube with one end open and the other closed. Growth appears to have been periodic with successive shell layers forming within older layers. Each added layer was slightly elevated from the previous layer at the proximal end and was asymmetrically placed within the older layer so that only a portion of the new shell layer was fused to the previous layer. This type of growth left a relatively large unminerialized area between the shell layers which was often partially or fully occluded by early marine cements. The thin shell layers exhibit both plastic and brittle deformation and were likely formed of a rigid CaCO3-impregnated organic-rich material. Often the shell layers are preferentially dolomitized suggesting an original mineralogy of high-magnesian calcite. Both species in the Nama Group formed thickets, or perhaps bioherms, and this sedentary and gregarious habit suggests that Cloudina was probably a filter-feeding metazoan of at least a cnidarian grade of organization. The unusual shell structure of Cloudina gives rise to a characteristic suite of taphonomic and diagenetic features that can be used to identify Cloudina-bearing deposits within the Nama Group and in other terminal Proterozoic deposits around the world. Species of Cloudina occur in limestones from Brazil, Spain, China, and Oman in sequences consistent with a latest Proterozoic age assignment. In addition, supposed lower Cambrian, pre-trilobitic, shelly fossils from northwest Mexico and the White-Inyo Mountains in California and Nevada, including Sinotubulites, Nevadatubulus, and Wyattia, are all either closely related to or con-generic with Cloudina. Hence, it is probable that these outcrops are latest Proterozoic in age, and that Cloudina or Cloudina-like organisms were widely distributed at that time. It is possible, moreover, to suggest that metazoan biomineralization occurred on a global scale by the latest Proterozoic, at the same time that evidence for complex multicellularity and locomotion in animals appears in siliciclastic "Ediacaran" rocks in the form of body and trace fossils.}, } @article {pmid2390002, year = {1990}, author = {Anders, A and Anders, F and Zechel, C and Schleenbecker, U and Smith, A}, title = {[Attempts at analyzing the initiation of the initial processes of carcinogenesis based on the Xiphophorus melanoma model].}, journal = {Archiv fur Geschwulstforschung}, volume = {60}, number = {4}, pages = {249-263}, pmid = {2390002}, issn = {0003-911X}, mesh = {Animals ; *Carcinogens ; *Cyprinodontiformes ; Genes, Regulator ; Hybridization, Genetic ; Inositol/metabolism ; Melanoma, Experimental/chemically induced/*genetics/metabolism ; Mutation ; Oncogenes ; }, abstract = {Certain backcross hybrids (BC8-22) of a spotted X. maculatus (platyfish) and a non-spotted X. helleri (swordtail; recurrent parent) are highly sensitive to mutagenic carcinogens and, after a latent period of 8 to 12 months, develop melanoma of unicellular origin that is genealogically related to the spots of the platyfish. Sensitivity to the carcinogen or susceptibility to melanoma, respectively, are inherited in a Mendelian fashion and can be assigned to a "tumor gene-complex" (Tu-complex) consisting probably of almost 20 genes. The Tu-complex is located at the end of an autosome or sex chromosome, and is largely deregulated by crossing conditioned replacement of platyfish chromosome carrying regulatory genes (tumor suppressor genes, oncostatic genes, antioncogenes) for the Tu-complex by swordtail chromosomes lacking them. The melanoma-free condition of these BC-hybrids depends upon the skin-specific regulatory gene Bs (body side) that requires impairment in a pigment cell precursor for the outgrowth of melanoma. Structural mutations involving different breakpoints indicate that the signal for melanoma formation comes from a particular region of the Tu-complex where an accessory v-erb B related oncogene (x-erb B*a; 85% homology to the human EGF receptor gene) is located. Northern blot analyses of the melanoma cell line showed an about 20-fold overexpression of x-erbB*a. Both the inositol lipid turnover [(3H)inositol incorporated into phosphoinositides], and the xiphophorine pp60x-src kinase activity that are assumed to be causally involved in tumor formation showed a remarkable elevation in the melanoma as compared to the normal tissue (brain) of the tumorous and non-tumourous (with or without the Tu-complex) segregants. Other BC hybrids carrying the Tu-complex but lacking the linked regulatory gene develop melanoma "spontaneously". This kind of melanoma occurs early in the course of life, is of multicellular origin, and is inherited as a Mendelian character. In contrast to the BC hybrids requiring somatic mutation for melanoma formation, both inositol, lipid turnover and x-src activity are remarkable enhanced in both melanoma and normal tissues. A mutant of the laller BC hybrids carrying in addition of the Tu-complex the homozygous oncostatic gene g (g/g, "golden") that arrests pigment cell differentiation in the stem cell stage is incapable to develop melanoma spontaneously. Nevertheless it shows the elevation of inositol lipid turnover and x-src activity in its always healthy tissues. Following treatment with tumor promoters such as TPA and steroid hormones pigment cell differentiation recovers and melanoma of multicellular origin develops within 4 to 8 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid2300560, year = {1990}, author = {Lake, JA}, title = {Origin of the Metazoa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {87}, number = {2}, pages = {763-766}, pmid = {2300560}, issn = {0027-8424}, mesh = {Animal Population Groups/*classification/genetics ; Animals ; Annelida/classification ; *Biological Evolution ; Mollusca/classification ; Phylogeny ; RNA, Ribosomal/*genetics ; RNA, Ribosomal, 18S/genetics ; }, abstract = {The origin of the multicellular animals has been investigated by rate invariant analysis of 18S rRNA sequences. These analyses indicate that (i) the Metazoa is a monophyletic taxon; (ii) the Deuterostomia is a monophyletic taxon; (iii) the Annelida-Mollusca lineage is the sister group of an arthropod subgroup; and (iv) the last common ancestor of the Annelida-Mollusca lineage is most parsimoniously derived from a segmented, hemocoelic ancestor with an open circulatory system.}, } @article {pmid2145898, year = {1990}, author = {Gàti, I and Bergström, M and Westerberg, G and Csòka, K and Muhr, C and Carlsson, J}, title = {Effects of prostaglandin and leukotriene inhibitors on the growth of human glioma spheroids.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {26}, number = {7}, pages = {802-807}, doi = {10.1016/0277-5379(90)90156-n}, pmid = {2145898}, issn = {0959-8049}, mesh = {Arachidonic Acids/antagonists & inhibitors ; Dexamethasone/pharmacology ; Glioma/*pathology ; Humans ; Indomethacin/pharmacology ; Ketoprofen/pharmacology ; *Leukotriene Antagonists ; Lipoxygenase Inhibitors ; Masoprocol/pharmacology ; Mitosis/drug effects ; Prostaglandin Antagonists/*pharmacology ; Quinacrine/pharmacology ; Tumor Cells, Cultured/*drug effects ; }, abstract = {Established cell-lines of human glioma origin were cultured as multicellular spheroids or as monolayers. Volume growth and 3H-thymidine labelling were analysed for the spheroids after continuous exposure to drugs interfering with the release of arachidonic acid and the production of prostaglandins and leukotrienes. Comparative measurements were made on monolayer cultures. The cyclo-oxygenase inhibitor indomethacin enhanced growth at intermediate concentrations (0.5-5.0 micrograms/ml) but reduced growth at 50 micrograms/ml. The dual cyclo-oxygenase and lipoxygenase inhibitor ketoprofen had a significant inhibitory effect on growth and cell proliferation of spheroids at high concentration (50 micrograms/ml). The weak lipoxygenase inhibitor NDGA (quinone-form) decreased growth whereas the strong lipoxygenase inhibitor NDGA (hydroquinone-form) did not reduce growth rate but significantly decreased cell proliferation. Quinacrine reduced the spheroid growth rate although dexamethasone had no effects. Thus, inhibitors of the arachidonic acid cascade had growth inhibitory effects in the spheroid tumour model as well as in cells cultured as monolayers.}, } @article {pmid2102547, year = {1990}, author = {Lins de Barros, HG and Esquivel, DM and Farina, M}, title = {Magnetotaxis.}, journal = {Science progress}, volume = {74}, number = {295 Pt 3}, pages = {347-359}, pmid = {2102547}, issn = {0036-8504}, mesh = {*Bacterial Physiological Phenomena ; Biological Evolution ; *Electromagnetic Fields ; Ferrosoferric Oxide ; Humans ; Iron/metabolism ; *Magnetics ; Oxides/metabolism ; }, abstract = {The ability of magnetotactic bacteria to orientate and navigate along geomagnetic lines is due to intracellular magnetic particles. These are enclosed within a membrane to form a magnetosome, a specialized organelle of magnetotactic organisms. The magnetic crystallite of many of the magnetotactic bacteria and algae is the iron oxide magnetite (Fe3O4) but recently a multicellular bacterial aggregate has been found to contain magnetic iron sulphide. Magnetotactic bacteria are found in regions of low oxygen pressure. Those of the Northern hemisphere are north-seeking while those of the Southern hemisphere are south-seeking. The opposite polarity of their internal magnets enables both types to travel to the deeper, less oxygenated, regions of their aqueous environments.}, } @article {pmid2090373, year = {1990}, author = {Ruvinsky, AO and Agulnik, AI}, title = {Gametic imprinting and the manifestation of the fused gene in the house mouse.}, journal = {Developmental genetics}, volume = {11}, number = {4}, pages = {263-269}, doi = {10.1002/dvg.1020110404}, pmid = {2090373}, issn = {0192-253X}, mesh = {Animals ; Cloning, Molecular ; Embryonic and Fetal Development/*genetics ; Female ; *Gene Expression ; *Genes, Dominant ; *Genes, Suppressor ; Genetic Linkage ; Genotype ; Haplotypes ; Male ; Mice ; Mutation ; Phenotype ; }, abstract = {The phenomenon of gametic imprinting in mammals has raised developmentally relevant questions concerning the manifestation and inheritance of genes with variable penetrance. The dominant fused (Fu) gene located on chromosome 17 is one of the few good cases demonstrating the phenomenon in mice. The Fu mutation has a maternal effect. We have previously shown that the t12 haplotype significantly lowers the penetrance of Fu in female Fu/t12 offspring. Results of reciprocal matings of the heterozygotes for Fu indicated that the Fu of maternal origin has a lowered level of penetrance. The dominant suppressors located outside chromosome 17, in contrast to t12 residing in it, had stronger effects on the manifestation of Fu, decreasing its penetrance to 8-17%. Experimental evidence is presented that the pathway via which Fu passes to the zygote nucleus during gametogenesis through successive generations has a marked effect on its penetrance. Based on this evidence, patterns of genetic imprinting are described. A survey of genetic imprinting allowed us to distinguish two developmental phases, gametic and zygotic. The hypothesis for the gametic phase of the development of multicellular organisms suggests that it proceeds from initialization, a process thought to ensure the freeing of chromosomes from redundant epigenetic information and their preparation for the consecutive developmental cycle.}, } @article {pmid2583872, year = {1989}, author = {Pervez, S and Kirkland, SC and Epenetos, AA and Mooi, WJ and Evans, DJ and Krausz, T}, title = {Effect of polarity and differentiation on antibody localization in multicellular tumour spheroid and xenograft models and its potential importance for in vivo immunotargeting.}, journal = {International journal of cancer}, volume = {44}, number = {5}, pages = {940-947}, doi = {10.1002/ijc.2910440532}, pmid = {2583872}, issn = {0020-7136}, mesh = {Adenocarcinoma/immunology/*pathology ; Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Neoplasm/*immunology ; Antigens, Neoplasm/*metabolism ; Cell Compartmentation ; Cell Differentiation ; Colonic Neoplasms/immunology/*pathology ; Epithelium/immunology/ultrastructure ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Mice ; Mice, Nude ; Microscopy, Electron ; Neoplasm Transplantation ; Organoids ; Rectal Neoplasms/immunology/*pathology ; Tumor Cells, Cultured ; }, abstract = {Two monoclonal antibodies (MAbs) AUAI and HMFGI recognize antigens located on different membrane domains of polarized epithelial cells. We have assessed the accessibility of these antigens in multicellular tumour spheroids produced in culture using a well-polarized (HRA-19) and a non-polarized cell line (LoVo) of human large-bowel carcinoma origin. Multicellular spheroids of HRA-19 cells develop polarity, so that the membrane which is in contact with the culture medium (apical) becomes antigenically distinct from the membrane facing the centre of the spheroids (basolateral). This was confirmed by immunostaining sections of spheroids with 2 MAbs, AUAI and HMFGI. AUAI recognizes an antigen located exclusively on the basolateral membranes of polarized epithelial cells, and stained only internal membranes in spheroid sections. Conversely HMFGI, which recognizes an antigen located on the apical membranes, stained only the periphery of the spheroids. These 2MAbs were then radiolabelled with 125I and incubated with live spheroids for 4 hr at 37 degrees C. Autoradiographs of spheroid sections showed a marked difference between the 2 MAbs. 125I-HMFGI-radioantibody localized exclusively on the spheroid surface in a pattern identical to the in vitro immunostaining pattern, while 125I-AUAI radioantibody showed no binding in spite of the uniform presence of antigen on all tumour cells basolaterally. This appeared to be the result of the inaccessibility of basolateral antigenic sites in well-polarized epithelial cells because of the tight junctions connecting these cells at their apical surfaces. In contrast to the HRA-19 cell line LoVo, spheroids do not develop polarity; as a result, when stained with AUAI, variable antigenic expression all over the cell surface was seen. Autoradiographs of these spheroids showed 125I-AUAI binding with a penetration to a depth of about 1-3 cells, while HMFGI which shows no reactivity with this cell line in vitro, did not bind. This phenomenon was further investigated in xenografts of the HRA-19 cell line. It was shown that in a well-differentiated adenocarcinoma where the tumour cells forming acini are arranged in a polarized fashion, the luminal antigenic sites may be inaccessible to the injected MAb. The striking differences in binding of MAbs on polarized and unpolarized tumours indicate the importance of cell polarization and exact location of antigenic sites for in vivo immunotargeting.}, } @article {pmid2808034, year = {1989}, author = {Schwachöfer, JH and Crooijmans, RP and van Gasteren, JJ and Hoogenhout, J and Jerusalem, CR and Kal, HB and Theeuwes, AG}, title = {Radiosensitivity of different human tumor cells lines grown as multicellular spheroids determined from growth curves and survival data.}, journal = {International journal of radiation oncology, biology, physics}, volume = {17}, number = {5}, pages = {1015-1020}, doi = {10.1016/0360-3016(89)90149-1}, pmid = {2808034}, issn = {0360-3016}, mesh = {Cell Division/*radiation effects ; Cell Survival/*radiation effects ; Humans ; *Radiation Tolerance ; Radiotherapy Dosage ; Tumor Cells, Cultured/*radiation effects ; }, abstract = {Five human tumor cell lines were grown as multicellular tumor spheroids (MTS) to determine whether multicellular tumor spheroids derived from different types of tumors would show tumor-type dependent differences in response to single-dose irradiation, and whether these differences paralleled clinical behavior. Multicellular tumor spheroids of two neuroblastoma, one lung adenocarcinoma, one melanoma, and a squamous cell carcinoma of the oral tongue, were studied in terms of growth delay, calculated cell survival, and spheroid control dose50 (SCD50). Growth delay and cell survival analysis for the tumor cell lines showed sensitivities that correlated well with clinical behavior of the tumor types of origin. Similar to other studies on melanoma multicellular tumor spheroids our spheroid control dose50 results for the melanoma cell line deviated from the general pattern of sensitivity. This might be due to the location of surviving cells, which prohibits proliferation of surviving cells and hence growth of melanoma multicellular tumor spheroids. This study demonstrates that radiosensitivity of human tumor cell lines can be evaluated in terms of growth delay, calculated cell survival, and spheroid control dose50 when grown as multicellular tumor spheroids. The sensitivity established from these evaluations parallels clinical behavior, thus offering a unique tool for the in vitro analysis of human tumor radiosensitivity.}, } @article {pmid2776218, year = {1989}, author = {Wilson, KM and Siegal, G and Lord, EM}, title = {Tumor necrosis factor-mediated cytotoxicity by tumor-associated macrophages.}, journal = {Cellular immunology}, volume = {123}, number = {1}, pages = {158-165}, doi = {10.1016/0008-8749(89)90276-1}, pmid = {2776218}, issn = {0008-8749}, support = {CA 28332/CA/NCI NIH HHS/United States ; T32-CA-09363/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Binding, Competitive ; Cell Line ; Cytotoxicity Tests, Immunologic ; *Cytotoxicity, Immunologic ; Female ; Immune Sera/pharmacology ; Macrophages/*immunology/metabolism ; Mice ; Mice, Inbred BALB C ; Peritoneal Cavity ; Recombinant Proteins ; Sarcoma, Experimental/immunology ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/biosynthesis/*immunology ; }, abstract = {We have directly demonstrated that macrophages present within solid EMT6 mammary tumors (of BALB/c origin) produce TNF-alpha (TNF). These tumor-associated macrophages lysed WEHI-164, a TNF-sensitive cell line, very efficiently. This cytotoxicity was abrogated in the presence of anti-TNF antisera. In contrast, EMT6 cells, the tumor from which the macrophages were obtained, were not effectively lysed by the macrophages and were 100-fold less sensitive to lysis by recombinant mouse TNF. Thus, marked heterogeneity exists among tumors regarding sensitivity to TNF-mediated cytotoxicity. Similarly, macrophages which infiltrate into EMT6 multicellular spheroids implanted into the peritoneal cavity as well as free cells within the cavity exhibited TNF-mediated cytotoxicity of WEHI-164 cells, but failed to lyse EMT6 cells. The kinetics of lysis by these cells was similar to that of recombinant mouse TNF.}, } @article {pmid2575705, year = {1989}, author = {Maruyama, IN and Miller, DM and Brenner, S}, title = {Myosin heavy chain gene amplification as a suppressor mutation in Caenorhabditis elegans.}, journal = {Molecular & general genetics : MGG}, volume = {219}, number = {1-2}, pages = {113-118}, pmid = {2575705}, issn = {0026-8925}, mesh = {Animals ; Blotting, Southern ; Caenorhabditis/*genetics ; DNA/metabolism ; *Gene Amplification ; Myosins/*genetics ; Polymorphism, Restriction Fragment Length ; Restriction Mapping ; *Suppression, Genetic ; }, abstract = {In the nematode, Caenorhabditis elegans, the body wall muscles contain paramyosin and two different types of myosin heavy chain, MHC A and MHC B. In mutants that do not express MHC B or that express defective paramyosin, muscle structure is disrupted and movement is impaired. Second site mutations in the sup-3 locus partially reverse these defects and are correlated with a 2- to 3-fold increase in the accumulation of the MHC A isoform. The sup-3 mutations occur at a high frequency (10(-4] after ethyl methanesulfonate (EMS) mutagenesis. This is comparable to the average EMS-induced mutation rate per gene in C. elegans. In this paper we show that the sup-3 mutation is an amplification of the structural gene for the MHC A protein, myo-3. We employed genomic Southern hybridization with MHC gene-specific probes in order to measure the copy number of the myo-3 gene relative to that of the MHC B gene, unc-54. We have identified the putative amplification junctions for these sup-3 alleles using a set of cosmid clones which encompass myo-3 region. Although it has been suggested that gene amplification plays an important role in evolution, there are few known cases of gene amplification in the germ line cells of multicellular organisms. The results shown here provide a clear example of a heritable gene amplification event that occurs at a high frequency in the germ line. Similar events may thus represent the initial event in the evolution of new function and in the formation of multigene families.}, } @article {pmid2777647, year = {1989}, author = {Schwachöfer, JH and Crooijmans, RP and van Gasteren, JJ and Hoogenhout, J and Jerusalem, CR and Kal, HB and Theeuwes, AG}, title = {Repair of sublethal damage in two human tumor cell lines grown as multicellular spheroids.}, journal = {International journal of radiation oncology, biology, physics}, volume = {17}, number = {3}, pages = {591-595}, doi = {10.1016/0360-3016(89)90111-9}, pmid = {2777647}, issn = {0360-3016}, mesh = {Carcinoma, Squamous Cell/genetics/pathology ; Cell Aggregation ; Cell Line ; DNA Repair/*radiation effects ; Humans ; In Vitro Techniques ; Neuroblastoma/genetics/pathology ; Radiation Dosage ; Radiation Tolerance ; Tumor Cells, Cultured/*radiation effects ; }, abstract = {Multicellular tumor spheroids (MTS) provide a suitable in vitro model to study radiation sensitivity of tumor cells. Two cell lines of human origin, obtained from a neuroblastoma (NB-100) and a squamous cell carcinoma (HN-1), were exposed to graded doses (4-9 Gy) of radiation with 18 MV photons. Radiation was applied either as a single or as a split dose with an interval of 6 hr to determine the extent of sublethal damage repair. Treated spheroids regrew at approximately the same growth rate as control multicellular tumor spheroids, preceded by a static or regression phase. Radiation response was quantified in terms of regrowth delay, expressed as the time needed for treated spheroids to obtain an 8-fold increase of the initial volume at the time of irradiation. Data obtained from regrowth delay analysis were used to calculate the extent of sublethal damage repair, showing for the squamous cell carcinoma line a fractionally higher capacity to repair sublethal damage than the neuroblastoma line. Repair increased with larger dose fractions in both cell lines. Our results show that multicellular tumor spheroids from the two cell lines used in this study are best applicable at relatively high total radiation doses. This makes multicellular tumor spheroids a suitable model for the in vitro evaluation of clinical treatment rationales such as hyperfractionation.}, } @article {pmid2477661, year = {1989}, author = {Franciolini, F and Petris, A}, title = {Evolution of ionic channels of biological membranes.}, journal = {Molecular biology and evolution}, volume = {6}, number = {5}, pages = {503-513}, doi = {10.1093/oxfordjournals.molbev.a040562}, pmid = {2477661}, issn = {0737-4038}, mesh = {Animals ; *Biological Evolution ; Calcium/metabolism ; *Ion Channels ; Membrane Potentials ; Membranes/*metabolism ; Paramecium/metabolism ; Phylogeny ; Potassium/metabolism ; Receptors, Cholinergic/metabolism ; Sodium/metabolism ; }, abstract = {This paper presents a view of the evolution and phylogenetic distribution of ionic channels of biological membranes. The view is based on the assumptions that ionic channels (1) appeared very early in the history of life, (2) have evolved from a common ancestor, and (3) have been subjected to evolutionary pressure to reach precision and high speed of signaling. We propose that Ca2+ was the intracellular messenger and modulator of the most primitive biological systems, which implies that the first channel to appear may have been a calcium channel. Then, very soon the entire group of potassium channels evolved from the calcium channel to improve the shape of signals and to restore initial conditions. Sodium channels probably appeared relatively late, diversifying from calcium channels in the early metazoan groups. Mainly because Na+ ions do not interfere with cellular metabolism (thus allowing the inward current--and, consequently, the speed of conduction--to be greatly increased), sodium channels probably proved advantageous in the generation of the action potential, and selection replaced calcium channels with sodium channels in this function. Finally, with the acquisition of multicellularity, channels responsible for synaptic transmission appeared. The case of the acetylcholine receptor channel is briefly discussed.}, } @article {pmid2686117, year = {1989}, author = {Poethig, S}, title = {Genetic mosaics and cell lineage analysis in plants.}, journal = {Trends in genetics : TIG}, volume = {5}, number = {8}, pages = {273-277}, doi = {10.1016/0168-9525(89)90101-7}, pmid = {2686117}, issn = {0168-9525}, mesh = {Chimera ; Microscopy, Electron, Scanning ; *Mosaicism ; *Plants, Toxic ; Tobacco/*genetics/growth & development/ultrastructure ; }, abstract = {The use of genetic mosaics for cell lineage analysis has revealed several important features of plant development. All multicellular organs in higher plants are polyclonal in origin. Although primordial cell lineages have fairly regular fates, the fate of any given cell within these lineages cannot be accurately predicted. Cell fate appears to be determined by the final location of a cell rather than by its history.}, } @article {pmid2736729, year = {1989}, author = {Berlin, JR and Cannell, MB and Lederer, WJ}, title = {Cellular origins of the transient inward current in cardiac myocytes. Role of fluctuations and waves of elevated intracellular calcium.}, journal = {Circulation research}, volume = {65}, number = {1}, pages = {115-126}, doi = {10.1161/01.res.65.1.115}, pmid = {2736729}, issn = {0009-7330}, support = {HL-25675/HL/NHLBI NIH HHS/United States ; HL-36974/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Calcium/metabolism/pharmacology/*physiology ; Electrophysiology ; Fluorescence ; Heart/*physiology ; Intracellular Membranes/*metabolism ; Myocardial Contraction ; Myocardium/*cytology/metabolism ; Osmolar Concentration ; }, abstract = {Activation of the transient inward current (ITI) by a rise in intracellular calcium concentration ([Ca2+]i) is believed to be responsible for generating triggered cardiac arrhythmias. In this study, the cellular basis of the rise in [Ca2+]i that activates ITI and aftercontractions in single rat ventricular myocytes was examined. [Ca2+]i was measured both indirectly by cell contraction and directly with fura-2. Under conditions that caused steady-state [Ca2+]i to increase (i.e., calcium overload) membrane repolarization after a voltage-clamp depolarization resulted in the appearance of ITI that was similar in many respects to that observed in multicellular preparations. This ITI occurred at the same time that [Ca2+]i spontaneously increased and preceded the aftercontraction by 60-90 msec. However, ITI recorded from a single cell was variable in time course and amplitude (unlike that observed in multicellular preparations). Examination of cell contraction and digital imaging of fura-2 fluorescence showed that ITI was often associated with propagating regions of increased [Ca2+]i, which arose from discrete sites of origin within the cell. Apparently synchronous aftercontractions could also be associated with multiple propagating waves of [Ca2+]i. The variation in the time course and amplitude of ITI in single cells appeared to be due to changes in the location and number of sites of origin for the waves of [Ca2+]i. After the first aftercontraction and ITI, desynchronization of the sites of origin of increased [Ca2+]i occurred, and this resulted in a decrease in the amplitude of ITI and an increase in its duration. We conclude that the variability seen in single cells arises from changes in the pattern of spontaneous Ca2+ release. Such phenomena will seriously complicate interpretation of multicellular data, even when [Ca2+]i is measured directly.}, } @article {pmid2716835, year = {1989}, author = {Perasso, R and Baroin, A and Qu, LH and Bachellerie, JP and Adoutte, A}, title = {Origin of the algae.}, journal = {Nature}, volume = {339}, number = {6220}, pages = {142-144}, doi = {10.1038/339142a0}, pmid = {2716835}, issn = {0028-0836}, mesh = {Base Sequence ; Eukaryota/*genetics ; Molecular Sequence Data ; RNA, Ribosomal/*genetics ; }, abstract = {Eukaryotic algae are traditionally separated into three broad divisions: the rhodophytes, the chromophytes and the chlorophytes. The evolutionary relationships between these groups, their links with other eukaryotes and with other photosynthetic groups, such as euglenophytes and cryptophytes, have been the subject of much debate and speculation. Here we analyse partial sequences of the large (28S) cytoplasmic ribosomal RNA from ten new species of protists belonging to various groups of unicellular algae. By combining them with the homologous sequences from 14 other unicellular and multicellular eukaryotes, we show that rhodophytes, chromophytes and chlorophytes emerge as three distinct groups late among eukaryotes, that is, close to the metazoa-metaphytes radiation. This implies a relatively late occurrence of eukaryotic photosynthetic symbiosis. We also provide details of intra- and inter-phyla relationships.}, } @article {pmid2918040, year = {1989}, author = {Freyer, JP and Schor, PL}, title = {Regrowth kinetics of cells from different regions of multicellular spheroids of four cell lines.}, journal = {Journal of cellular physiology}, volume = {138}, number = {2}, pages = {384-392}, doi = {10.1002/jcp.1041380222}, pmid = {2918040}, issn = {0021-9541}, support = {CA-22585/CA/NCI NIH HHS/United States ; CA-36535/CA/NCI NIH HHS/United States ; RR-01315/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; *Cell Cycle ; Cell Division ; Cell Line ; Fibrosarcoma ; Glioma ; Humans ; Mammary Neoplasms, Experimental ; Melanoma ; Mice ; Tumor Cells, Cultured/*pathology ; }, abstract = {A basic understanding of the recruitment of quiescent tumor cells into the cell cycle would be an important contribution to tumor biology and therapy. As a first step in pursuing this goal, we have investigated the regrowth kinetics of cells from different regions in multicellular spheroids of rodent and human origin. Cells were isolated from four different depths within the spheroids using a selective dissociation technique. The outer cells were proliferating and resumed growth after replating with a 0-8-hour lag period, similar to cells from exponentially growing monolayers. With increasing depth of origin, the lag periods prior to regrowth increased to 2-3 times the monolayer doubling time; cells from plateau-phase monolayers showed a lag period of 1-1.5 times the doubling period. After resuming growth, all cells of a given cell line grew with the same doubling time and achieved the same confluency level. The inner spheroid cells and cells from plateau-phase monolayers had reduced clonogenic efficiencies. The inner cells were initially 1.5-3 times smaller than the outer cells, but began to increase in volume within 4 hours of replating. The fractions of S-phase cells were greatly decreased with increasing depth of origin in the spheroids; there were long delays prior to S-phase recovery after plating, to a maximum of 1-1.5 times the normal doubling time. These results suggest that those quiescent cells from spheroids and monolayers which are able to reenter the cell cycle are predominantly in the G1-phase. However, quiescent cells from the innermost spheroid region require approximately twice as long to enter normal cell cycle traverse as cells from plateau-phase monolayers. The selective dissociation method can isolate very pure populations of proliferating and quiescent cells in a rapid and nonperturbing manner; this system will be valuable in further characterizing quiescent cells from spheroids.}, } @article {pmid2702623, year = {1989}, author = {Mertens, F and Heim, S and Jin, YS and Johansson, B and Mandahl, N and Biörklund, A and Wennerberg, J and Jonsson, N and Mitelman, F}, title = {Basosquamous papilloma. A benign epithelial skin tumor with multiple cytogenetic clones.}, journal = {Cancer genetics and cytogenetics}, volume = {37}, number = {2}, pages = {235-239}, doi = {10.1016/0165-4608(89)90054-x}, pmid = {2702623}, issn = {0165-4608}, mesh = {Aged ; *Chromosome Aberrations ; Female ; Gene Rearrangement ; Humans ; Papilloma/*genetics ; Skin Neoplasms/*genetics ; }, abstract = {Cytogenetic analysis of short-term cultures from a basosquamous papilloma revealed the following mosaic karyotype: 46,XX,t(2;5)(q31;q31),t(8;15)(p21;q21)/46,XX,t(7;17)(p13;p13)/47,XX, t(3;20)(q12;p13),+7/46,XX,t(1:12)(p12;q13). The finding of four abnormal, cytogenetically unrelated clones suggests a multicellular origin of this benign skin tumor. None of the structural rearrangements encountered have previously been associated with neoplasia.}, } @article {pmid2909809, year = {1989}, author = {Heim, S and Mitelman, F}, title = {Cytogenetically unrelated clones in hematological neoplasms.}, journal = {Leukemia}, volume = {3}, number = {1}, pages = {6-8}, pmid = {2909809}, issn = {0887-6924}, mesh = {Chromosome Aberrations/classification/*genetics ; Chromosome Disorders ; Clone Cells/classification ; Humans ; Karyotyping ; Leukemia/*genetics ; Lymphoma/classification/*genetics ; Myelodysplastic Syndromes/classification/*genetics ; Myeloproliferative Disorders/classification/*genetics ; }, abstract = {We have reviewed literature data on 6,306 cases of hematological neoplasia--acute and chronic lymphatic and myeloid leukemias (CML excepted), myelodysplastic and chronic lymphoproliferative and myeloproliferative disorders, and malignant lymphomas--with the goal of quantitatively ascertaining how often cytogenetically unrelated clones occur in these diseases. Unexpectedly wide variations were found: in ANLL, unrelated clones were present in 1.1% of the 2,506 known cases with chromosome abnormalities characterized with banding technique; in the various myelodysplastic (MDS) and chronic myeloproliferative (CMD) disorders (total number of cases 1,299) the frequency was 4.3% and in lymphatic malignancies 1.3% (total case number 2,501). In the latter group the proportions varied between 0.4% and 0.6% in ALL and malignant lymphoma (ML) to as much as 6.2% in CLD and 7.3% in CLL. Some karyotypic abnormalities were encountered more often than would be expected from their general frequency in the various diseases. This discrepancy was particularly evident in MDS and CMD, where 5q- was found in slightly less and +8 in somewhat more than half of the 56 cases. Furthermore, these two aberrations were found as the only changes in the two coexisting clones in one-fourth of the material. Although if viewed in isolation these data would undoubtedly be best explained by assuming a multicellular origin of the neoplasm, it is entirely possible that what are cytogenetically perceived as unrelated clones could be subclones with some invisible aberration in common. If so, this interpretation indicates that changes like +8 and 5q-, both of which are common rearrangements in bone marrow neoplasms, are actually secondary changes that develop during tumor progression.}, } @article {pmid2687098, year = {1989}, author = {Hickey, DA and Benkel, BF and Magoulas, C}, title = {Molecular biology of enzyme adaptations in higher eukaryotes.}, journal = {Genome}, volume = {31}, number = {1}, pages = {272-283}, doi = {10.1139/g89-045}, pmid = {2687098}, issn = {0831-2796}, mesh = {Adaptation, Biological/*genetics ; Animals ; Base Sequence ; *Biological Evolution ; Enzymes/*genetics ; Gene Expression Regulation ; Genes, Regulator/genetics ; Humans ; Molecular Sequence Data ; Polymorphism, Genetic ; Selection, Genetic ; alpha-Amylases/genetics ; }, abstract = {Multicellular eukaryotes have evolved complex homeostatic mechanisms that buffer the majority of their cells from direct interaction with the external environment. Thus, in these organisms long-term adaptations are generally achieved by modulating the developmental profile and tissue specificity of gene expression. Nevertheless, a subset of eukaryotic genes are still involved in direct responses to environmental fluctuations. It is the adaptative responses in the expression of these genes that buffers many other genes from direct environmental effects. Both microevolutionary and macroevolutionary patterns of change in the structure and regulation of such genes are illustrated by the sequences encoding alpha-amylases. The molecular biology and evolution of alpha-amylases in Drosophila and other higher eukaryotes are presented. The amylase system illustrates the effects of both long-term and short-term natural selection, acting on both the structural and regulatory components of a gene--enzyme system. This system offers an opportunity for linking evolutionary genetics to molecular biology, and it allows us to explore the relationship between short-term microevolutionary changes and long-term adaptations.}, } @article {pmid2668061, year = {1989}, author = {Csordas, A}, title = {A proposal for a possible role of nucleosome positioning in the evolutionary adjustment of introns.}, journal = {The International journal of biochemistry}, volume = {21}, number = {5}, pages = {455-461}, doi = {10.1016/0020-711x(89)90124-9}, pmid = {2668061}, issn = {0020-711X}, mesh = {*Biological Evolution ; *Introns ; *Nucleosomes ; Prokaryotic Cells ; }, abstract = {1. Prokaryotes and yeast have mostly intronless genes, whereas the presence of a large number of extended introns are characteristic of the genes of of multicellular eukaryotic organisms which, however, as an exception also have a few intronless genes. 2. According to the current view, the lack of introns in prokaryotic organisms and yeast is due to the selective pressure of a short cell division time. On the other hand, the presence of introns in multicellular eukaryotic organisms is explained by the lack of selective forces against them. 3. In the present hypothesis it is proposed that introns were used as tools in the course of evolution for the organization of eukaryotic genes within the repeating units of nucleosomes, since the distinct DNA conformations of the nucleosome core particle and of the linker region, respectively, represent a constraint for the positioning of genes. 4. Recently it was shown that initiation of transcription is inhibited when the promoter sequence is within a nucleosome. 5. Since the nucleosomal organization of DNA leads to a severely deformed DNA helix and recognition of sequences by regulatory proteins is likely to depend on the conformation of the double helix, it is postulated that for the different sizes of eukaryotic genes which have to be organized within repeating units of nucleosomes, introns provided the flexibility of adjustment for the positioning of regulatory sequences, by drifting in length, sequence and position.}, } @article {pmid2665023, year = {1989}, author = {Barbieri, FD}, title = {The origin of Metazoa and Weismann's germ line theory.}, journal = {Rivista di biologia}, volume = {82}, number = {1}, pages = {61-74}, pmid = {2665023}, issn = {0035-6050}, mesh = {Animals ; *Germ Cells ; }, abstract = {Weismann's theory asserts that the continuity of germ cells throughout the entire life cycle is insured by the protection of the somatic cells which represent a distinct lineage. On the basis of embryological data and the organization pattern displayed by some highly differentiated unicellular organisms, it is postulated that the soma of multicellular animals has probably arisen as an accessory structure for an initially unicellular system.}, } @article {pmid3052859, year = {1988}, author = {Chernyak, L and Tauber, AI}, title = {The birth of immunology: Metchnikoff, the embryologist.}, journal = {Cellular immunology}, volume = {117}, number = {1}, pages = {218-233}, doi = {10.1016/0008-8749(88)90090-1}, pmid = {3052859}, issn = {0008-8749}, mesh = {Allergy and Immunology/*history ; Animals ; Embryology/history ; History, 19th Century ; Immunity, Cellular ; Phagocytosis ; }, abstract = {Metchnikoff must be viewed first as an embryologist, who, influenced by the Darwinian currents of the 1860s and 1870s, sought to establish a genetic and embryologic unity in phylogeny. His principal early theory that the mesoderm was the origin of endodermal structures enabled him to extend the observation of mesodermal digestive processes to a theory of immunity. Observation of amoeboid phagocytosis was not novel, but Metchnikoff's scientific investigations had prepared him to interpret this activity as a manifestation of a generalized property of the mesoderm. Earlier observers noted the presence of microorganisms and particles in leukocytes, and the notion of phagocytosis had previously been entertained, but only Metchnikoff recognized the importance of phagocytosis in a general scheme of inflammation and to develop an experimental model for its investigation. The observation was thus viewed not solely as an issue of pathology, but rather as a contribution to Metchnikoff's general idea of genetic unity and his hypothesis of a primordial multicellular organism, Parenchymella, later called Phagocytella. It is striking that he ultimately viewed phagocytosis as a question of immunity, considering the context of his research activities, which had been confined to evolution and biology of development. To demonstrate how the famous Messina experiments were extended to a new theory of immunity requires formulating Metchnikoff's recognition of both the importance of phagocytosis for his mesodermal theory and a more general theory of pathology. The result was the genesis of a new idea, immunity.}, } @article {pmid3251965, year = {1988}, author = {Sugawa, T}, title = {[Cancer and therapy for it--from gynecological standpoints].}, journal = {Nihon Sanka Fujinka Gakkai zasshi}, volume = {40}, number = {8}, pages = {961-968}, pmid = {3251965}, issn = {0300-9165}, mesh = {Adjuvants, Immunologic/therapeutic use ; Aging/pathology ; Antineoplastic Agents/therapeutic use ; Biological Evolution ; Blood Proteins/physiology ; Cell Division ; Cisplatin/therapeutic use ; Combined Modality Therapy ; Female ; Genital Neoplasms, Female/drug therapy/immunology/*therapy ; Humans ; Immune Tolerance ; Immunotherapy ; Life Expectancy ; Ovarian Neoplasms/diagnosis/drug therapy ; Remission Induction ; }, abstract = {Life phenomena have been studied scientifically for more than 160 years. Meanwhile many excellent technology and methodology which human race created have been used in the field of medicine. Analytical research for the constitution of life and impediments to life has remarkably advanced. Pathophysiology of many diseases has been clarified and reasonable and effective treatment for disorders has been organized. Many disorders which showed high mortality in the past are now listed as one of minor diseases in the textbook. However, the disease which cause is unclear and which deprives human race of life still exists. That is "CANCER". The society of medicine devotes the greatest energies to abolish the cancer. I am going to talk about the physiological characteristics of "the cancer in human race" from the gynecological standpoints and to present some facts of studies about the therapy for cancer in our department. I. Evolution of human and cancer 1. Life of species and life of individuals In the development from uni-nuclear cell creature to multicellular entity, to give new generation sexual reproduction was out-lasted for the adaptation to environment advantageously after the spread out of mutant gene in this entity. With this evolution, a living creature divided its cells into two types. One is somatic cells which would die in certain period and the other is germ cells which would not die on principle in good environment. In short well evolved living entity clearly established individual life span for the first time and its constituent, that is somatic cells demonstrated "AGEING" phenomena regulating life span.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid3294034, year = {1988}, author = {Van Wijk, R and Schamhart, DH}, title = {Regulatory aspects of low intensity photon emission.}, journal = {Experientia}, volume = {44}, number = {7}, pages = {586-593}, pmid = {3294034}, issn = {0014-4754}, mesh = {Animals ; Biophysical Phenomena ; Biophysics ; *Cell Physiological Phenomena ; Free Radicals ; Light ; *Luminescent Measurements ; Oxidation-Reduction ; Plants ; Radiation ; Saccharomyces cerevisiae/physiology ; }, abstract = {Photon emission from unicellular and multicellular organisms has been a subject of study for many decennia. In contrast to the well-known phenomenon of bioluminescence originating in luciferin-luciferase reactions, low intensity emission in the visible region of the electromagnetic spectrum has been found in almost every species studied so far. At present, the nomenclature of this phenomenon has not crystallized and it is referred to by a variety of names, such as mitogenetic radiation 29, dark luminescence 7, low-level chemiluminescence 20,36, and biophotons 57. Particular attention has been focussed on the relationship between photon emission and the regulation of various aspects of cellular metabolism, although in many cases quantitative data are still lacking. Throughout the history of this field of research the question of a functional biological role of the low intensity emission has been repeatedly raised; this is reflected, for instance, in the heterogeneity of the terms used to describe it. The discussion concerns the possible participation of photons of low intensity in intra- and intercellular communication. This paper reviews literature on the metabolic regulation of low intensity emission, as well as the regulation of photon emission initiated by external light. Furthermore, recent data are discussed with respect to a possible biocommunicative function of low intensity photon emission.}, } @article {pmid3226138, year = {1988}, author = {Bodnar, JW}, title = {A domain model for eukaryotic DNA organization: a molecular basis for cell differentiation and chromosome evolution.}, journal = {Journal of theoretical biology}, volume = {132}, number = {4}, pages = {479-507}, doi = {10.1016/s0022-5193(88)80086-9}, pmid = {3226138}, issn = {0022-5193}, mesh = {Animals ; Cell Differentiation ; *Cell Physiological Phenomena ; Chromatin/physiology ; DNA/*physiology ; DNA Replication ; Eukaryotic Cells/*physiology ; Gene Expression Regulation ; Humans ; *Models, Genetic ; }, abstract = {A model for eukaryotic chromatin organization is presented in which the basic structural and functional unit is the DNA domain. This simple model predicts that both chromosome replication and cell type-specific control of gene expression depend on a combination of stable and dynamic DNA-nuclear matrix interactions. The model suggests that in eukaryotes, DNA regulatory processes are controlled mainly by the intranuclear compartmentalization of the specific DNA sequences, and that control of gene expression involves multiple steps of specific DNA-nuclear matrix interactions. Predictions of the model are tested using available biochemical, molecular and cell biological data. In addition, the domain model is discussed as a simple molecular mechanism to explain cell differentiation in multi-cellular organisms and to explain the evolution of eukaryotic genomes consisting mainly of repetitive sequences and "junk" DNA.}, } @article {pmid3356007, year = {1988}, author = {Freyer, JP}, title = {Role of necrosis in regulating the growth saturation of multicellular spheroids.}, journal = {Cancer research}, volume = {48}, number = {9}, pages = {2432-2439}, pmid = {3356007}, issn = {0008-5472}, support = {CA-22585/CA/NCI NIH HHS/United States ; CA-36535/CA/NCI NIH HHS/United States ; RR-01315/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Cell Cycle ; *Cell Division ; Cell Line ; Cricetinae ; Culture Media ; DNA/analysis ; Growth Inhibitors/analysis ; Humans ; Mice ; Necrosis ; Rats ; Tumor Cells, Cultured/pathology ; }, abstract = {Growth curves for multicellular spheroids of 15 different tumor and normal cell lines were characterized by doubling times which decreased with increasing growth until a stable saturation was attained. In spite of the identical and constant conditions during growth, the size at saturation varied by factors of 67 in spheroid volume and 75 in cell content. These saturation sizes showed no correlation with the monolayer doubling times or clonogenic efficiencies, the initial spheroid growth rate or clonogenic capacity at saturation, the cell packing density, or the species of origin and type of cell line. There was a strong correlation between the maximal spheroid size and the size at which necrosis initially developed, suggesting control by necrosis. Crude extracts prepared from spheroids with extensive necrosis showed dose-dependent cytostatic and cytotoxic activities against monolayer cultures, while similar extracts from spheroids without necrosis had little effect. This activity was also detected in the culture medium to which the large spheroids had been exposed prior to preparation of extracts, suggesting that the responsible factor(s) can diffuse through the spheroid. The extract from spheroids of one cell line inhibited the growth and clonogenicity of four other cell lines, including human diploid fibroblasts. DNA content profiles measured during exposure to this extract showed that the cytostatic effect was not due to the arrest of cells in a specific cell cycle phase. The cell volumes were increased during culture in medium containing the extract from spheroids with extensive necrosis. These data support the hypothesis that growth saturation in spheroids is regulated by factors produced, released, or activated during the process of necrosis and suggest that these toxic factors have potential therapeutic use.}, } @article {pmid3288248, year = {1988}, author = {Glimelius, B and Norling, B and Nederman, T and Carlsson, J}, title = {Extracellular matrices in multicellular spheroids of human glioma origin: increased incorporation of proteoglycans and fibronectin as compared to monolayer cultures.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {96}, number = {5}, pages = {433-444}, doi = {10.1111/j.1699-0463.1988.tb05327.x}, pmid = {3288248}, issn = {0903-4641}, mesh = {Cell Adhesion ; Cell Division ; Chromatography, Gel ; Extracellular Matrix/analysis/*ultrastructure ; Extracellular Space/analysis ; Fibronectins/*analysis ; Fluorescent Antibody Technique ; Glioma/analysis/*ultrastructure ; Glycosaminoglycans/analysis/biosynthesis ; Humans ; Hyaluronic Acid/analysis/biosynthesis ; Microscopy, Electron ; Proteoglycans/*analysis ; Trypsin/pharmacology ; Tumor Cells, Cultured ; }, abstract = {Tumor spheroids were cultured from five human glioma cell lines which differed considerably in their relative amount and composition of glycosaminoglycans (GAG), fibronectin and other extracellular matrix (ECM) components when grown as monolayer cultures. These differences were also evident when the cells were grown as spheroids. Under the 3-dimensional geometry of the spheroid system, there was, however, generally a more extensive ECM. Especially noteworthy was the presence of a small proteoglycan, probably a dermatan sulphate proteoglycan, in the ECM of the spheroids, but not in the monolayers. Noteworthy was also the appearance of fibronectin in spheroids which did not show any staining for fibronectin when grown as monolayer. The two spheroid types (U-87MG, U-105MG) with the most extensive matrix, and with the lowest proportion of hyaluronic acid (HA), had a low proliferation rate, whereas the three other spheroid types (U-118MG, U-138MG, U-251MG) with a less extensive ECM, and a relatively high production of HA had a much higher proliferation rate. These data provide further evidence for the usefulness of culturing cell lines as spheroids in the process of understanding important cell biological phenomena.}, } @article {pmid3344017, year = {1988}, author = {Arnold, A and Staunton, CE and Kim, HG and Gaz, RD and Kronenberg, HM}, title = {Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas.}, journal = {The New England journal of medicine}, volume = {318}, number = {11}, pages = {658-662}, doi = {10.1056/NEJM198803173181102}, pmid = {3344017}, issn = {0028-4793}, support = {AM 07028/AM/NIADDK NIH HHS/United States ; AM 11794/AM/NIADDK NIH HHS/United States ; }, mesh = {Adenoma/genetics/*pathology ; Adult ; Aged ; DNA/analysis ; Dosage Compensation, Genetic ; Female ; Genetic Linkage ; Humans ; Hyperplasia ; Hypoxanthine Phosphoribosyltransferase/genetics ; Middle Aged ; Nucleic Acid Hybridization ; Parathyroid Glands/pathology ; Parathyroid Hormone/*genetics ; Parathyroid Neoplasms/genetics/*pathology ; X Chromosome ; }, abstract = {Previous work based on the relative tissue content of glucose-6-phosphate dehydrogenase isoenzymes suggested that parathyroid adenomas, like primary hyperplasia, may be multicellular (not clonal) in origin. We have reexamined this issue by using two independent molecular genetic methods. We report tumor-cell-specific restriction-fragment-length alterations involving the parathyroid hormone gene from two human parathyroid adenomas. These abnormal restriction fragments indicate that in each case a clonal proliferation of cells was present and also suggest that DNA alterations involving the parathyroid hormone locus may be important in the tumorigenesis or clonal evolution of some parathyroid adenomas. In addition, we used a restriction-fragment-length polymorphism in an X-linked gene (hypoxanthine phosphoribosyltransferase) to examine the clonality of eight parathyroid adenomas in women. Of these eight adenomas, six had the DNA hybridization pattern of monoclonality, and two had an equivocal pattern. None of five hyperplastic parathyroid glands had a monoclonal pattern. We conclude that some (and perhaps many) single parathyroid adenomas are monoclonal neoplasms. Our observations suggest that there is a fundamental biologic difference between parathyroid adenomas and primary hyperplasia--a difference that could prove useful in distinguishing these entities clinically.}, } @article {pmid3198701, year = {1988}, author = {Weinberg, WC and Iannaccone, PM}, title = {Clonality of preneoplastic liver lesions: histological analysis in chimeric rats.}, journal = {Journal of cell science}, volume = {89 (Pt 3)}, number = {}, pages = {423-431}, doi = {10.1242/jcs.89.3.423}, pmid = {3198701}, issn = {0021-9533}, support = {CA29078/CA/NCI NIH HHS/United States ; ES03498/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; *Chimera ; Clone Cells ; Liver/*pathology ; Liver Neoplasms/*pathology ; Phenotype ; Precancerous Conditions/*pathology ; Rats ; }, abstract = {The clonality of chemically induced altered hepatocellular foci was examined in rat liver. Chimeric rats composed of two histologically distinguishable cell lineages were placed on an initiation-promotion protocol for liver cancer induction. This resulted in multiple lesions of altered enzyme expression. These altered hepatocellular foci are generally considered to be initiated sites susceptible to cancer formation. The cellular origins of these lesions were determined by aligning sections demonstrating cell lineage with serial sections stained for altered enzyme expression. Analysis included 110 areas of deficient ATPase (EC 3.6.1.3) activity and 59 glucose-6-phosphatase (EC 3.1.3.9; G-6-Pase) deficient lesions, 744 foci of re-expression of gamma-glutamyl transpeptidase (EC 2.3.2.2; gamma-GT), and decreased glycogen mobilization (187 lesions). Of the 1100 focal enzyme alterations, 1054 were shown to be composed entirely of cells from a single lineage of the two lineages present in the mosaic tissue. Multiple alterations occurred within given lesions. Lesions with up to four phenotypic alterations were found to consist of cells of a single lineage. These results suggest that individual enzyme-altered foci are clonal in origin and that phenotypic heterogeneity within altered hepatocellular foci is due to lesion progression within a clonal population and not to a multicellular derivation.}, } @article {pmid3338091, year = {1988}, author = {McMorrow, LE and Wolman, SR and Bornstein, S and Talmadge, JE}, title = {Irradiation-induced marker chromosomes in a metastasizing murine tumor.}, journal = {Cancer research}, volume = {48}, number = {4}, pages = {999-1003}, pmid = {3338091}, issn = {0008-5472}, support = {N01-23910//PHS HHS/United States ; }, mesh = {Animals ; *Chromosome Aberrations ; Chromosomes/*radiation effects ; Female ; Karyotyping ; Melanoma, Experimental/*genetics/pathology ; Mice ; Mice, Inbred C3H ; Neoplasm Metastasis/*pathology ; }, abstract = {We have used irradiation to induce marker chromosome formation in a metastasizing murine tumor with a stable karyotype. The induced recombinant chromosomes then served to determine whether metastases were of clonal or multicellular origin. Cumulative data were obtained from four series of experiments on spontaneous metastases originating from tumors grown from irradiated cells; 20 of these metastases expressed unique chromosomal alterations consistent with a clonal origin. The majority of metastasis-derived cell populations remain stable with respect to their marker chromosomes in culture as well as in successive animal transplantation. In several instances, however, chromosomal instability was sufficient to obscure the cellular origins of individual metastases. A few metastases showed mixed chromosomal patterns initially that were consistent with multicellular origin, but repeat examinations have revealed a chromosomal instability which persisted during propagation in culture. The frequency of chromosomal recombinants in metastases from the combined series was sufficient to suggest biological and statistical significance. The morphology of recombinants was not associated with radiation dose but appeared as an apparently random response of the tumor population in different experiments. Analysis of chromosomal markers by banding techniques was performed to determine if specific chromosomes or chromosomal sites were associated with tumor cells from metastatic foci (a host-selected subpopulation with a metastatic phenotype). Our results did not reveal preferential involvement of whole chromosomes or intrachromosomal sites in recombinant formation.}, } @article {pmid3338976, year = {1988}, author = {Sowers, KR and Gunsalus, RP}, title = {Adaptation for growth at various saline concentrations by the archaebacterium Methanosarcina thermophila.}, journal = {Journal of bacteriology}, volume = {170}, number = {2}, pages = {998-1002}, pmid = {3338976}, issn = {0021-9193}, mesh = {Adaptation, Physiological ; Cell Membrane/ultrastructure ; Culture Media ; Euryarchaeota/drug effects/*growth & development/ultrastructure ; Microscopy, Electron ; Phenotype ; Polysaccharides, Bacterial/biosynthesis ; Sodium Chloride/*pharmacology ; }, abstract = {We report the ability of Methanosarcina thermophila TM-1 to adapt and grow in media containing NaCl concentrations of 0.005 to 1.2 M. When adapted to marine NaCl concentrations, this species ceased to produce the heteropolysaccharide outer layer typically formed by species of nonmarine origin. concomitant with this adaptation, M. thermophila ceased to grow as multicellular aggregates and existed solely in single-cell form. The sodium ion concentration was critical for the adaptation process, although magnesium ion appeared to contribute to the cell wall stability of single cells. The results suggest that these archaebacteria possess regulatory systems that enable them to adapt to environments with a wide range of saline concentrations.}, } @article {pmid3390124, year = {1988}, author = {Fasolo, A and Panzica, GC and Viglietti-Panzica, C and Renda, T and D'Este, L}, title = {Comparative chemical anatomy of the brain: concepts and methods.}, journal = {Basic and applied histochemistry}, volume = {32}, number = {1}, pages = {15-30}, pmid = {3390124}, issn = {0391-7258}, mesh = {Anatomy, Comparative/*methods ; Animals ; Brain Chemistry ; Humans ; Immunohistochemistry/methods ; Neuropeptides/analysis/genetics/physiology ; Phylogeny ; }, abstract = {The study of neuropeptides represents an appropriate playground for comparative and evolutionary research. Comparative analysis can give insight into the conservative pattern of intercellular transmission molecules, possibly bound both to some evolutionary antiquity and to cellular constraints. In the same time it can teach us how modulation has occurred at molecular, cellular, multicellular levels in order to give the species-specific functional organization. Using some examples from vertebrate central neurons system (CNS) immunocytochemical analyses, the results so far obtained suggest the rise of a new comparative chemical neuroanatomy. The rationale of "what" and "why" we are comparing is, however, needed in order to understand constancy, heterogeneity or else trends toward complexity in the distribution of neuropeptides.}, } @article {pmid2830635, year = {1988}, author = {Venter, JC and di Porzio, U and Robinson, DA and Shreeve, SM and Lai, J and Kerlavage, AR and Fracek, SP and Lentes, KU and Fraser, CM}, title = {Evolution of neurotransmitter receptor systems.}, journal = {Progress in neurobiology}, volume = {30}, number = {2-3}, pages = {105-169}, doi = {10.1016/0301-0082(88)90004-4}, pmid = {2830635}, issn = {0301-0082}, mesh = {Animals ; *Biological Evolution ; Guanine Nucleotides/physiology ; Humans ; Neurons/metabolism/*physiology ; Receptors, Adrenergic/metabolism/*physiology ; Receptors, Cholinergic/metabolism/*physiology ; Receptors, Neurotransmitter/metabolism/*physiology ; Sequence Homology, Nucleic Acid ; }, abstract = {The presence of hormones, neurotransmitters, their receptors and biosynthetic and degradative enzymes is clearly not only associated with the present and the recent past but with the past several hundred million years. Evidence is mounting which indicates substantial conservation of protein structure and function of these receptors and enzymes over these tremendous periods of time. These findings indicate that the evolution and development of the nervous system was not dependent upon the formation of new or better transmitter substances, receptor proteins, transducers and effector proteins but involved better utilization of these highly developed elements in creating advanced and refined circuitry. This is not a new concept; it is one that is now substantiated by increasingly sophisticated studies. In a 1953 article discussing chemical aspects of evolution (Danielli, 1953) Danielli quotes Medawar, "... endocrine evolution is not an evolution of hormones but an evolution of the uses to which they are put; an evolution not, to put it crudely, of chemical formulae but of reactivities, reaction patterns and tissue competences." To also quote Danielli, "In terms of comparative biochemistry, one must ask to what extent the evolution of these reactivities, reaction patterns and competences is conditional upon the evolution of methods of synthesis of new proteins, etc., and to what extent the proteins, etc., are always within the synthetic competence of an organism. In the latter case evolution is the history of changing uses of molecules, and not of changing synthetic abilities." (Danielli, 1953). Figure 4 outlines a phylogenetic tree together with an indication of where evidence exists for both the enzymes that determine the biosynthesis and metabolism of the cholinergic and adrenergic transmitters and their specific cholinergic and adrenergic receptors. This figure illustrates a number of important points. For example, the evidence appears to show that the transmitters and their associated enzymes existed for a substantial period before their respective receptor proteins. While the transmitters and enzymes appear to exist in single cellular organisms, there is no solid evidence for the presence of adrenergic or cholinergic receptors until multicellular organisms where the receptors appear to be clearly associated with specific cellular and neuronal communication (Fig. 4). One can only speculate as to the possible role for acetylcholine and the catecholamine in single cell organisms.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid3430409, year = {1987}, author = {Quiñones-Maldonado, V and Renaud, FL}, title = {Effect of biogenic amines on phagocytosis in Tetrahymena thermophila.}, journal = {The Journal of protozoology}, volume = {34}, number = {4}, pages = {435-438}, doi = {10.1111/j.1550-7408.1987.tb03208.x}, pmid = {3430409}, issn = {0022-3921}, support = {RR8102/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Biogenic Amines/*pharmacology ; Dopamine/pharmacology ; Epinephrine/pharmacology ; Norepinephrine/pharmacology ; Phagocytosis/*drug effects ; Serotonin/pharmacology ; Tetrahymena/drug effects/*physiology ; }, abstract = {Stimulation of phagocytosis by serotonin and catecholamines in Tetrahymena grown in proteose-peptone medium proved to be concentration dependent, the optimal concentrations being approximately 0.1 to 1.0 microM. The serotonergic antagonists, spiperone, and metergoline, also stimulated the process, whereas the beta- and alpha-adrenergic antagonists, propranolol, alprenolol, and ergocryptine, had no effect or inhibited phagocytosis. A wide variety of derivatives of the biogenic amines had no effect on phagocytosis, demonstrating the specificity of recognition mechanism for neurohormones in Tetrahymena. Such hormones act by at least two independent mechanisms, one for adrenergic agonists, another for dopamine. Presumably, recognition mechanisms for hormones in protozoa resemble in some respects those in multicellular organisms, therefore bespeaking a common origin.}, } @article {pmid2445211, year = {1987}, author = {Garvin, AJ and Sullivan, JL and Bennett, DD and Stanley, WS and Inabnett, T and Sens, DA}, title = {The in vitro growth, heterotransplantation, and immunohistochemical characterization of the blastemal component of Wilms' tumor.}, journal = {The American journal of pathology}, volume = {129}, number = {2}, pages = {353-363}, pmid = {2445211}, issn = {0002-9440}, support = {AM 32889/AM/NIADDK NIH HHS/United States ; CA 37887/CA/NCI NIH HHS/United States ; CA 39239/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antigens, Surface/analysis ; Cell Division ; Cells, Cultured ; Humans ; Immunohistochemistry ; Keratins/analysis ; Kidney Neoplasms/*pathology/ultrastructure ; Male ; Mice ; Mice, Nude ; Microscopy, Electron ; Neoplasm Transplantation ; Transplantation, Heterologous ; Vimentin/analysis ; Wilms Tumor/*pathology/ultrastructure ; }, abstract = {Wilms' tumor has been proposed to originate from a developmental abnormality of the metanephric blastema. This undifferentiated component of Wilms' tumors has previously eluded efforts for in vitro growth. Blastema from a "classical" Wilms' tumor was transplanted into nude mice and passaged through 12 generations of heterotransplantation. Tumors from heterotransplants were grown for 12 serial passages in a serum-free growth medium supplemented with hormones and conditioned media from human kidney proximal tubule cells. The blastema initially grew on a collagen-fetal calf serum matrix as multicellular spheroids, and the cells proliferating from the rim of the spheroids had a flattened shape. Pulse-labeling with bromodeoxyuridine (BrdU) identified the proliferating cell population as blastemal in origin. Except for a loss of extracellular matrix, ultrastructural studies demonstrated morphologic similarities in the cultured cells, compared with the primary tumor and heterotransplants. Lectin histochemical stains for the peanut lectin (PNA) and immunohistochemical stains for cytokeratin (CYTO), vimentin (VIM), and epithelial membrane antigen (EMA) were performed on the original tumor, successive heterotransplants, and cells grown in vitro. The PNA stained the surface of the blastemal cells after sialidase digestion in the original tumor, heterotransplants, and cultured cells. The blastema of the original tumors was negative for CYTO and EMA but reactive for vimentin. This lack of differentiation was maintained in heterotransplants through 12 passages. However, blastemal cells demonstrated coexpression of CYTO and VIM intermediate filaments when grown in a serum-free medium on a matrix material. These studies demonstrate that the blastemal component of Wilms' tumor can be successfully grown in culture, passaged in nude mouse heterotransplants, and shown to undergo early stages of blastemal differentiation in vitro by growth in serum-free medium. This in vitro system provides a model for testing the factors that influence the growth and differentiation of the blastemal component of Wilms' tumors.}, } @article {pmid3115244, year = {1987}, author = {Hemmingsen, EA and Hemmingsen, BB and Owe, JO and Andersen, HT}, title = {Lack of bubble formation in hypobarically decompressed cells.}, journal = {Aviation, space, and environmental medicine}, volume = {58}, number = {8}, pages = {742-746}, pmid = {3115244}, issn = {0095-6562}, support = {HL 16855/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Bacterial Physiological Phenomena ; *Cell Physiological Phenomena ; Cell Wall/physiology ; *Decompression ; Erythrocytes/physiology ; Euglena gracilis/physiology ; Gases ; Humans ; In Vitro Techniques ; Tetrahymena pyriformis/physiology ; }, abstract = {Suspensions of human erythrocytes or of unicellular microorganisms (Tetrahymena pyriformis, Euglena gracilis, Escherichia coli, and Microcyclus aquaticus) were equilibrated with nitrogen gas pressures up to 200 atm and rapidly decompressed to hypobaric pressures below the vapor point of water. The intracellular environments proved to be very tolerant to the gas supersaturations induced. None or only a few cells were damaged in each case, and bubbles were never observed intracellularly after decompression. In view of such extreme tolerances, it is doubtful that bubbles originate intracellularly during decompression of multicellular organisms, in which bubbles occur with far lower gas supersaturations, unless the tolerances are greatly affected by extensive mechanical deformations of the cells or by the presence of internalized particles with bubble-promoting properties.}, } @article {pmid3556142, year = {1987}, author = {Svirnovskiĭ, AI}, title = {[Anti-leukemia resistance and growth-regulating molecules in hematopoietic tissue].}, journal = {Eksperimental'naia onkologiia}, volume = {9}, number = {2}, pages = {3-7}, pmid = {3556142}, issn = {0204-3564}, mesh = {Growth Substances/*immunology ; Hematopoietic System/*immunology ; Humans ; Immunity, Innate ; Leukemia/*immunology ; }, abstract = {The analyzed data from literature suggest that the growth-regulating molecules of the hematopoietic tissue are a part of the antileukemic defence system of the body. This component of the antitumour resistance is the first one formed during the multicellular organism evolution. It is of special significance in the tissue stimulated to proliferation in which the number of antiblastic defence cell effectors diminishes in the regenerating tissue while the number of progenitor cells having the oncogenic potential increases.}, } @article {pmid3435389, year = {1987}, author = {Berkovich, SY}, title = {Informational structure of the developmental tree of multi-cellular organisms.}, journal = {Basic life sciences}, volume = {42}, number = {}, pages = {23-33}, doi = {10.1007/978-1-4613-1939-9_2}, pmid = {3435389}, issn = {0090-5542}, mesh = {Animals ; *Biological Evolution ; Chromosomes/physiology ; DNA/genetics ; *Models, Genetic ; Twins, Monozygotic ; }, } @article {pmid3332496, year = {1987}, author = {Lagerspetz, KY}, title = {Temperature effects on different organization levels in animals.}, journal = {Symposia of the Society for Experimental Biology}, volume = {41}, number = {}, pages = {429-449}, pmid = {3332496}, issn = {0081-1386}, mesh = {*Adaptation, Physiological ; Animals ; Cell Membrane/physiology ; Cell Physiological Phenomena ; Cell Survival ; *Temperature ; }, abstract = {One of the central concepts in present biology is the recognition of different organization levels and their hierarchical array. Complex multicellular animals are constituted of organ systems, the organs of cells, the cells of organelles, membranes, and molecules. The primary effects of many environmental factors (e.g. light, concentrations of ions and molecules) can be delimited mainly to one level. Temperature, being the macroscopic physical measure of the random motion of smallest material particles, affects directly the animal life at all organization levels. The special physical nature of temperature means also, that during the history of life, organisms have always been subjected to temperature variations. Many different ways to evade the pervasive effects of temperature have been evolved during the course of evolution. The study of the temperature relations of organisms can therefore give models for other branches of environmental biology. The temperature limits and relations of an animal cannot be explained by the temperature relations and limits of its cells without taking into account such interactions between different types of cells, which are found only through the study of the organs. Also, the temperature limits and relations of animal cells cannot be explained just through the study of the constituent molecules. The possible interactions of the molecules (e.g. lipids and proteins in a cell membrane) are so manifold and complex that in order to ascertain the relative importance of them in the temperature relations of the cells we must rely in part on studies done on organelles (e.g. on the plasma membrane). The study of the thermal biology of animal cells thus exemplifies the situation often found in biology: the attainment of a reductive explanation is not always a one-way deduction, but it may involve modifications of the lower level concepts according to the knowledge derivable only from studies of the higher level systems.}, } @article {pmid3311215, year = {1987}, author = {Bagby, GC}, title = {Production of multilineage growth factors by hematopoietic stromal cells: an intercellular regulatory network involving mononuclear phagocytes and interleukin-1.}, journal = {Blood cells}, volume = {13}, number = {1-2}, pages = {147-159}, pmid = {3311215}, issn = {0340-4684}, mesh = {Biological Evolution ; *Bone Marrow Cells ; *Cell Communication ; Colony-Stimulating Factors/metabolism ; Growth Substances/*metabolism ; Hematopoietic Stem Cells/classification/cytology/drug effects ; Humans ; Interleukin-1/*physiology ; Monokines ; Phagocytes/*physiology ; Proteins/*physiology ; }, abstract = {In the past 8 years, our group has carried out a series of in-vitro studies designed to characterize the role of mononuclear phagocytes as regulators of human hematopoiesis. The results of this program of investigation, some of which are reviewed below, led to the discovery that mononuclear phagocytes are more efficient recruitors of growth factor release by other cells than they are direct stimulators of progenitor cell growth. Specifically, mononuclear phagocytes release soluble factors (MRA) that stimulate other cells, including vascular endothelial cells, skin fibroblasts, and marrow fibroblasts, to release multilineage hematopoietic growth factors. Experiments designed to purify and characterize these monokines indicated unambiguously that the MRA that stimulates granulocyte/macrophage colony stimulating factor (GM-CSF) release is interleukin-1 (IL-1). Based on these observations and recent observations by other groups on the hematopoietic effects of other monokines including tumor necrosis factor alpha, we argue that mononuclear phagocytes serve as important regulators of hematopoiesis by producing monokines that, in turn, induce the expression of multiple hematopoietic growth factor genes in stromal cells of the hematopoietic microenvironment. Because IL-1 molecules and the mononuclear phagocytes producing them are evolutionarily conserved, and in view of the heterogeneous nonhematopoietic effects of these monokines, studies on their role in hematopoiesis may also provide new understanding of the molecular evolution of multicellular organisms.}, } @article {pmid3124804, year = {1987}, author = {Smith-Sonneborn, J}, title = {Longevity in the protozoa.}, journal = {Basic life sciences}, volume = {42}, number = {}, pages = {101-109}, doi = {10.1007/978-1-4613-1939-9_7}, pmid = {3124804}, issn = {0090-5542}, mesh = {Aging ; Animals ; Ciliophora/genetics/growth & development ; Eukaryota/genetics/*growth & development ; Genes ; Longevity ; }, abstract = {In ciliates there are examples of cells which have different proliferation potential in the macronucleus. Those species with limited macronuclear proliferation potential require sex to activate the reserve nucleus. In terms of the capital investment theory, some ciliates invested in their spare nucleus without loss of their original potential, while others accumulated debts and needed the reserve account to maintain life. Other cells neglected maintenance of their reserve account and failed unless their venture capital account was not a self-sustaining venture. Sex provided access to the reserve account and had to occur before deterioration of the reserve account. The question is not when cellular immortality was lost, but rather when immortality was partitioned from a mortal segment. The separation provided the option both for senescence and evolution in multicellular organisms. In colonial flagellates, separation of cells with infinite and finite cell lifespan potential occurred in some species, while in others the separation did not involve loss of immortality. In colonial flagellates, sex did not become an obligate stage. The immortal cells are haploid and could not accumulate damage and live (in contrast with the diploids in the ciliated protozoans). The present theory predicts that differences between species or cells with infinite versus finite lifespan potential may reveal differences in the critical determinants of longevity. Senescence could arise as an accident, as well as a design of nuclear differentiation. Cells therefore may have a much greater reserve for totipotency than would be predicted if they were assumed to lose immortality simply by the act of differentiation.}, } @article {pmid3078725, year = {1987}, author = {Ohno, S}, title = {The ancestor of the adaptive immune system was the CAM system for organogenesis.}, journal = {Experimental and clinical immunogenetics}, volume = {4}, number = {4}, pages = {181-192}, pmid = {3078725}, issn = {0254-9670}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; *Biological Evolution ; Cell Adhesion Molecules/*genetics/immunology ; Chickens/genetics ; Dictyostelium/genetics/immunology ; Humans ; Immune System/*physiology ; Molecular Sequence Data ; Protein Conformation ; Sequence Homology, Nucleic Acid ; beta 2-Microglobulin/*genetics/immunology ; }, abstract = {The adaptive immune system as we understand it is uniquely possessed by vertebrate species and by none other. Nevertheless, it is generally thought that this system represents the ultimate sophistication of much older cell-cell interaction mechanisms. In this paper, I have suggested that plasma membrane cell adhesion proteins that were involved in ontogenic organogenesis since time immemorial were the ultimate ancestor of the adaptive immune system. N-CAM of the chicken for neuronal organogenesis already possesses four beta 2-microglobulin-like domains and it is this domain from which the adaptive immune system sprang. The germ for this beta 2-microglobulin-like domain is already found in the cell adhesion protein of the slime mold straddling the border between unicellular and multicellular eukaryotes. A slightly different version of the above view has recently been expressed by my colleagues.}, } @article {pmid2954844, year = {1987}, author = {Bückmann, D}, title = {Common origin and phylogenetic diversification of animal hormonal systems.}, journal = {Experientia. Supplementum}, volume = {53}, number = {}, pages = {155-166}, doi = {10.1007/978-3-0348-9291-9_11}, pmid = {2954844}, issn = {0071-335X}, mesh = {Animals ; Endocrine Glands/metabolism ; Hormones/*physiology ; Neurosecretion ; *Phylogeny ; Plants ; Sex Differentiation ; Species Specificity ; }, abstract = {The comparative view leads to the following main conclusions: Hormones are intercellular messengers in multicellular organisms. However, the receptor mechanism, the ability of forming receptors to substances in the cell's environment and the ability to synthesize most of the substances which serve as hormones in metazoans, are present in unicellular organisms, too. The main achievement of multicellular organisms in evolving hormonal mechanisms is due to their ability of differentiation. Though the whole genome and the ability to synthesize certain substances is, in principle, common to all body cells, the forming of certain substances and the ability to react to them in a certain way is delegated to certain cell groups only. This may be common to many intercellular messenger substances such as chalons, prostaglandins, morphogenetic and tissue-specific growth substances. A special feature in hormonal systems is that the two sites of release and reaction are distinct and are located at a distance from each other. Possibly this is the main or even the only difference from other intercellular messengers. However, it is of great functional importance because it enables hormones to control the temporal coordination of entirely different processes in different tissues located at a distance from each other or distributed all over the body. This feature is common to all compounds presently known as hormones. While the localization of receptors in target cells, as well as the nature of the releasing tissue or the mode of transport through the blood, may be too marrow borders for a definition (for instance in animal groups without a closed blood circulation system) the fact that there is transport over a distance is not. The fact that release and reaction sites are located at a distance from each other within the multicellular body may serve as a definition of "hormones' based on a common phylogenetic root and functional importance. On this common base different animal phyla have evolved different hormonal systems in relation to the particular problems of long distance temporal control of physiological processes posed by their special type of organization.}, } @article {pmid2883769, year = {1987}, author = {Antohi, S and Antohi-Talle, O}, title = {Viral oncogenes, proto-oncogenes and homoeotic genes related to cell proliferation and differentiation.}, journal = {Virologie}, volume = {38}, number = {1}, pages = {61-70}, pmid = {2883769}, issn = {0253-181X}, mesh = {Animals ; Cell Differentiation ; Cell Division ; Cloning, Molecular ; *Genes, Homeobox ; *Genes, Viral ; Humans ; Oncogene Proteins, Viral/genetics ; *Oncogenes ; *Proto-Oncogenes ; }, abstract = {Molecular studies on viral oncogenes and their products have led to the discovery of physiological proto-oncogenes, involved in the control of cell proliferation and gene activation. Other genetic and molecular investigations, initiated in Drosophila melanogaster and continued in different multicellular eukaryotes, have made evident the homoeotic genes, which are directly correlated with cell specialization, in the complex processes of differentiation and morphogenesis. Both gene classes are conserved to a high extent during evolution. They are involved in the eukaryotic mechanisms of differentiation control and proto-oncogenes, in particular, are related to malignant transformation. Some available data suggest a certain extent of relatedness between the gene products of both gene classes. A differentiation trigger model, including retroviral transposition, homoeotic genes and proto-oncogenes is discussed.}, } @article {pmid3540280, year = {1986}, author = {Gunderson, JH and McCutchan, TF and Sogin, ML}, title = {Sequence of the small subunit ribosomal RNA gene expressed in the bloodstream stages of Plasmodium berghei: evolutionary implications.}, journal = {The Journal of protozoology}, volume = {33}, number = {4}, pages = {525-529}, doi = {10.1111/j.1550-7408.1986.tb05656.x}, pmid = {3540280}, issn = {0022-3921}, support = {GM32964/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Biological Evolution ; *Genes ; Phylogeny ; Plasmodium berghei/*genetics ; RNA, Ribosomal/*genetics ; }, abstract = {We have determined the complete nucleotide sequence of the coding region of the small subunit rRNA gene expressed by bloodstream stages of the apicomplexan Plasmodium berghei. It is 2059 nucleotides long. Elements contributing to its relatively large size are all concentrated in regions known to be variable in length among eukaryotes. In a phylogenetic tree constructed from pairwise comparisons of eukaryotic small subunit rRNA sequences, the apicomplexan line branches at a rather early point in eukaryotic evolution before any multicellular kingdoms had yet appeared.}, } @article {pmid3733640, year = {1986}, author = {Erlichman, C and Tannock, IF}, title = {Growth and characterization of multicellular tumor spheroids of human bladder carcinoma origin.}, journal = {In vitro cellular & developmental biology : journal of the Tissue Culture Association}, volume = {22}, number = {8}, pages = {449-456}, pmid = {3733640}, issn = {0883-8364}, support = {CA29526/CA/NCI NIH HHS/United States ; }, mesh = {Anthraquinones/pharmacology ; Carcinoma/drug therapy/pathology ; Cell Division/drug effects ; Cell Line ; Humans ; Mitoxantrone ; Urinary Bladder Neoplasms/drug therapy/*pathology ; }, abstract = {We have examined the MGH-U1 human bladder carcinoma cell line and 12 primary bladder carcinoma biopsies for their ability to form spheroids in suspension culture and in multiwell dishes. MGH-U1 cells formed tightly packed spheroids with a necrotic center and viable rim whereas three sublines formed loose aggregates only. Spheroids formed from as few as 100 MGH-U1 cells placed into multiwells. MGH-U1 cells derived from spheroids formed new spheroids more rapidly and and consistently than cells derived from monolayer culture. Spheroid diameter increased at a rapid rate of approximately 100 microns/d in multiwell dishes, and necrosis occurred only in spheroids of diameter greater than 1 mm. Spheroids placed in spinner culture at a higher concentration (approximately 1.5 spheroids/ml) grew more slowly and developed necrosis at smaller diameters. The width of the viable rim of spheroids grown in spinner culture was maintained at approximately 190 microns over a wide range of spheroid diameters (400 to 1000 microns). Sequential trypsinization of spheroids, which stripped layers of cells from the spheroids, demonstrated no difference in the plating efficiency of cells derived from varying depths into the spheroid. Only one of the 12 primary bladder biopsy specimens demonstrated an ability to form spheroids. This biopsy, designated HB-10, formed spheroids that grew linearly over 40 d, formed colonies in methylcellulose culture and grew as xenografts in immune-deprived mice. These studies characterize the MGH-U1 spheroids that are useful in vitro models to study the effects of various treatments for solid tumors and demonstrate the limited capacity of cells from primary human bladder biopsies to form spheroids.}, } @article {pmid3459716, year = {1986}, author = {Fodstad, O and Brøgger, A and Bruland, O and Solheim, OP and Nesland, JM and Pihl, A}, title = {Characteristics of a cell line established from a patient with multiple osteosarcoma, appearing 13 years after treatment for bilateral retinoblastoma.}, journal = {International journal of cancer}, volume = {38}, number = {1}, pages = {33-40}, doi = {10.1002/ijc.2910380107}, pmid = {3459716}, issn = {0020-7136}, mesh = {Adolescent ; Cell Line ; Chromosome Banding ; Chromosome Deletion ; Eye Neoplasms/genetics/*pathology ; Femoral Neoplasms/*pathology/ultrastructure ; Humans ; Infant ; Lymphocytes/ultrastructure ; Male ; Microscopy, Electron, Scanning ; *Neoplasms, Multiple Primary ; Osteosarcoma/*pathology/ultrastructure ; Retinoblastoma/genetics/*pathology ; Translocation, Genetic ; }, abstract = {An osteosarcoma cell line, OHS, was established from a patient with multiple skeletal manifestations of osteosarcoma, developing after bilateral retinoblastoma. The tumor cells expressed sarcoma-associated antigens and showed rapid growth in monolayers and as multicellular spheroids. They formed distinct colonies in soft agar, and subcutaneous tumors in nude mice. Morphological studies indicated that OHS cells had retained important characteristics of the cells of origin. No deletion of the retinoblastoma genes on chromosome 13q14 could be demonstrated with the banding techniques used. However, cytogenetic studies revealed double minute chromosomes, as evidence of gene amplification, as well as translocations involving chromosomes 1,6,11 and 13. The OHS line can be used to study the genetic basis of tumor initiation and growth, and to elucidate factors predisposing for second primary cancers in retinoblastoma patients.}, } @article {pmid3638476, year = {1986}, author = {Agrell, U}, title = {Draft of a general stochastic theory of cancer and its possible experimental verification with monoclonal multiplication of repairing and immunological systems.}, journal = {Medical hypotheses}, volume = {20}, number = {3}, pages = {261-270}, doi = {10.1016/0306-9877(86)90042-3}, pmid = {3638476}, issn = {0306-9877}, mesh = {Age Factors ; Aging ; Biological Evolution ; *DNA Repair ; Diseases in Twins ; Humans ; Mutation ; Neoplasms/*etiology/genetics/immunology ; Oncogenes ; *Probability ; *Stochastic Processes ; Twins, Monozygotic ; }, abstract = {A general stochastic theory of cancer is outlined by applying to cancer the laws of quantum mechanics instead of the laws of traditional physics, especially with regard to the concept of cause. This theory is combined with the evolutionary theory on the one hand and the mutation theory of aging/death of multicellular beings consisting of somatic cells on the other. The cancer theory centers around the phenomenon of DNA mutating randomly by quantal steps. Because of mutations in the DNA in general as well as in the special DNA which codes for the DNA repairing systems the body is permeated in the course of time - via increasing losses of information in the DNA - with increasingly altered proteins which is observed as aging process. From this process of entropy the concept of the cancer cell is deduced: When the losses of information in a certain cell and also in the repairing and immunological systems have random concordances, cancer as a type of antigens comes into existence. Here the concept of CONCORDANCE OF "BLURRING" is introduced. This CONCORDANCE OF "BLURRING" occurs randomly approximately once among three times 60 000 billion cells, i.e. three human beings. The so-called "oncogenes" are integrated into this theory. It is proposed to test this theory using monozygotic twins both suffering from cancer: By injecting monoclonally multiplied immunological systems, eventually also repair-systems, from the respective other twin, the proposition is that the cancer would be cured in both twins. If this critical experiment is successful, one can cure human beings suffering from cancer by the same procedure, using those systems of their relatives. This treatment would cure the cancer to the extent to which there is a genetic correspondence in the sections of genes coding for these systems.}, } @article {pmid3516385, year = {1986}, author = {Blanton, RH and Lyte, M and Myers, MJ and Bick, PH}, title = {Immunomodulation by polyaromatic hydrocarbons in mice and murine cells.}, journal = {Cancer research}, volume = {46}, number = {6}, pages = {2735-2739}, pmid = {3516385}, issn = {0008-5472}, support = {CA-09210/CA/NCI NIH HHS/United States ; ES-03366/ES/NIEHS NIH HHS/United States ; ES-05323/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Anthracenes/toxicity ; Antibody Formation/*drug effects ; Benzo(a)pyrene/toxicity ; Benzopyrenes/*toxicity ; Cells, Cultured ; Female ; Hemolytic Plaque Technique ; Immunosuppressive Agents/toxicity ; Lipopolysaccharides/pharmacology ; Mercaptoethanol/pharmacology ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Tuberculin/pharmacology ; }, abstract = {Several functionally defined in vitro antibody generating systems were used to assess the immunomodulating mechanisms of the benzopyrenes. When benzo(a)pyrene (BaP) or benzo(e)pyrene (BeP) was incorporated into a T-dependent antibody (TDAb)-producing spleen cell culture system, dose- and time-dependent inhibition of plaque-forming cell responses was observed. Addition of BaP at concentrations as low as 0.002 microgram/ml (7.93 nM) resulted in suppression of the TDAb plaque-forming cell response. BeP-induced suppression was seen at the 2-microgram level (7.93 microM). Time course evaluations demonstrated an early requirement for either chemical in culture in order to induce significant suppression. In vitro incorporation of BaP and BeP into polyclonal antibody-generating cultures also resulted in a dose-related inhibition. Inhibition of these antibody responses was also noted following in vivo exposure of mice to BaP or BeP. Fourteen-day exposure of mice to BaP (40 mg/kg) resulted in 98% suppression of the TDAb response. Polyclonal antibody responses were reduced 50 to 66% following 7 days of chemical exposure. BeP caused 51% suppression of the TDAb response following 14-day exposure of animals. These studies indicate that the suppressive effects of the benzopyrenes are multicellular in origin, occur apart from the carcinogenic effects of the chemicals, and cannot be attributed merely to cellular toxicity.}, } @article {pmid3700166, year = {1986}, author = {Sutherland, R and Freyer, J and Mueller-Klieser, W and Wilson, R and Heacock, C and Sciandra, J and Sordat, B}, title = {Cellular growth and metabolic adaptations to nutrient stress environments in tumor microregions.}, journal = {International journal of radiation oncology, biology, physics}, volume = {12}, number = {4}, pages = {611-615}, doi = {10.1016/0360-3016(86)90070-2}, pmid = {3700166}, issn = {0360-3016}, support = {CA 11051/CA/NCI NIH HHS/United States ; CA-11198/CA/NCI NIH HHS/United States ; CA-20329/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Cycle ; Cricetinae ; Glucose/metabolism ; Heat-Shock Proteins/biosynthesis ; Humans ; In Vitro Techniques ; Mice ; Models, Biological ; Necrosis ; Neoplasms, Experimental/*metabolism/pathology ; Oxygen Consumption ; Stress, Physiological/*metabolism ; }, abstract = {Heterogeneity of cell subpopulation growth was significantly modulated by different oxygen and glucose environments and necrosis in multicellular tumor spheroids of rodent and human origin. PO2 profiles within spheroids measured with microelectrodes showed major differences associated with different oxygen and glucose supply conditions, indicating important interactions of these two substrates affecting oxygen consumption rates and cellular viability. Cellular interactions in association with the development of growth quiescence and differentiation changed oxygen consumption rates and slopes of PO2 profiles within spheroids. Protein synthesis in monolayer cells in culture was severely inhibited when exposed to extreme hypoxia, but certain proteins were synthesized at increased rates. Many of these oxygenated regulated proteins can also be induced by glucose deprivation. The data demonstrate cellular and subcellular changes in tumor models in vitro because of variations in oxygen and glucose supply. Many of these changes would be expected to occur in tumor microregions in vivo and could have important consequences for therapeutic responsiveness.}, } @article {pmid3707376, year = {1986}, author = {Gabaeva, NS}, title = {[Theory of the continuity of germ plasma according to the findings of modern biology].}, journal = {Arkhiv anatomii, gistologii i embriologii}, volume = {90}, number = {3}, pages = {5-16}, pmid = {3707376}, issn = {0004-1947}, mesh = {Biological Evolution ; Cell Differentiation ; Cell Nucleus/physiology ; Cleavage Stage, Ovum ; Cytoplasm/physiology ; Eukaryota/physiology ; Genetics ; Germ Cells/*cytology ; Gonads/embryology ; Species Specificity ; }, abstract = {The main principles on the theory of germ plasma by A. Weismann are briefly presented; a number of his genetic-embryological hypotheses proved to be prophetic. Modern notions on the germ plasma are critically discussed, as well as the resulting from them the conception on continuity of totipotent cells (the source of germ cells) in the line of generations, that is historically connected with M. Nussbaum--A. Weismann's notions on continuity of the embryonic pathway. The term totipotency is sometimes used inaccurately; it means ability to formation of a whole organism. In Metazoa zygota and isolated blastomeres, at a regulative type of development, and groups of somatic cells or fragments of the organism, at an asexual reproduction and somatic embryogenesis, possess this ability. In ontogenesis totipotency is lost both by the somatic and by the germ cells because of their specialization and is recreated with the beginning of every ontogenesis when zygota is formed. The germ cells are always a product of the organism--unicellular or multicellular, and their specialization in all its manifestations is the result of integrative influences of the organism as a whole of them. Certain reasons are presented for supporting ideas on germ cells as one of the lines of cell differentiation. The main, if not the only contradiction in the problem concerning relation of the germ and somatic cells is, at the present time, the thesis on continuity of totipotent cells in the line of generations.}, } @article {pmid3535427, year = {1986}, author = {Schwab, M}, title = {Malignant metamorphosis: developmental genes as culprits for oncogenesis in Xiphophorus.}, journal = {Advances in cancer research}, volume = {47}, number = {}, pages = {63-97}, doi = {10.1016/s0065-230x(08)60198-0}, pmid = {3535427}, issn = {0065-230X}, mesh = {Animals ; Carcinogens/toxicity ; Cell Differentiation ; Crosses, Genetic ; Cyprinodontiformes/*genetics ; DNA, Neoplasm/genetics ; Female ; Fish Diseases/*genetics/pathology ; Male ; Melanocytes/pathology ; Melanoma/genetics/pathology/*veterinary ; Oncogenes ; Pigmentation ; *Proto-Oncogenes ; }, abstract = {Neoplastic growth is a widespread developmental aberration among multicellular organisms ranging from primitive avertebrates such as coelenterates (Brien, 1961) and annelids (Cooper, 1969) to man. A major goal of the studies concerning neoplasia has been to obtain insight into its cellular and molecular basis, and it has been suggested as early as the beginning of this century that cellular genes are paramount in the etiology of neoplasis. Early support for this idea has been gained by Mendelian strategies applied to a number of experimental systems, such as Xiphophorus. During the last years molecular biology has provided some insight into the genetic mechanisms that might be involved in neoplasia in higher vertebrates, and it has been possible to identify proto-oncogenes as candidates for the agents directing cellular transformation and/or maintainance of the neoplastic state of the cell. The high degree of evolutionary conservation of the proto-oncogenes points to basic functions that these genes normally might have for the cell and at the same time indicates that crucial steps associated with tumorigenesis might take similar pathways in different classes of vertebrates. There are now four main lines of molecular evidence that relate cellular genes to neoplasia: insertional mutagenesis or chromosomal rearrangement that juxtaposes an exogenous or endogenous genetic element which augments gene expression next to a cellular gene, resulting in elevated expression (for review, see Varmus, 1982; Klein, 1983); gene amplification that results in an increase of the copy number and an elevated expression of a particular gene and, to date, has been found in tumors of humans and mice (for overviews, see Schwab et al., 1984; Schwab, 1985; Alitalo and Schwab, 1986); structural alteration of a cellular gene itself which results in the synthesis of an altered protein (Weinberg, 1982; Cooper, 1982); and generation of fusion genes as a result of gene translocation with possibly altered biological activities (for review, see Adams, 1985). It remains to be addressed in future experiments which genetic mechanisms are operative in development of tumors of genetic origin in Xiphophorus.}, } @article {pmid3082091, year = {1986}, author = {Sharma, AK}, title = {Evolution of cell and chromosome structure in eukaryote.}, journal = {Acta biotheoretica}, volume = {35}, number = {1-2}, pages = {69-76}, pmid = {3082091}, issn = {0001-5342}, mesh = {Animals ; *Biological Evolution ; Cells/*cytology ; Chromosomes/*ultrastructure ; Eukaryotic Cells/*cytology ; Genes, Regulator ; *Models, Genetic ; Prokaryotic Cells/cytology ; }, abstract = {The analysis of the data so far available indicates that eukaryotic chromosome with splicing characteristics appeared quite early in evolution possibly parallel and not sequential to the prokaryotic system. The endosymbiotic origin of the eukaryotic cell involved a primitive undifferentiated unicellular eukaryote and a photosynthetic or non-photosynthetic microbe. Certain regulatory genes of extra-cellular organelles were transferred later through molecular hybridization to the nucleus. The evolution of multicellularity and sexual reproduction led to the origin of innumerable eukaryotic forms in the late precambrian period. This new concept of the author can account for the evolution of complex eukaryotic chromosome and harmonious functioning of extra-cellular organelles with the nucleus. The concept also explains the sudden spurt of innumerable eukaryotic fossils at the early palaeozoic era.}, } @article {pmid3028248, year = {1986}, author = {Kaiser, D}, title = {Control of multicellular development: Dictyostelium and Myxococcus.}, journal = {Annual review of genetics}, volume = {20}, number = {}, pages = {539-566}, doi = {10.1146/annurev.ge.20.120186.002543}, pmid = {3028248}, issn = {0066-4197}, support = {AG02908/AG/NIA NIH HHS/United States ; GM23441/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Cell Aggregation ; Cell Communication ; Chemotaxis ; DNA Transposable Elements ; Dictyostelium/*growth & development/physiology ; *Gene Expression Regulation ; Myxococcales/*growth & development/physiology ; Spores, Bacterial ; Spores, Fungal ; }, } @article {pmid2861236, year = {1985}, author = {Roth, J and LeRoith, D and Collier, ES and Weaver, NR and Watkinson, A and Cleland, CF and Glick, SM}, title = {Evolutionary origins of neuropeptides, hormones, and receptors: possible applications to immunology.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {135}, number = {2 Suppl}, pages = {816s-819s}, pmid = {2861236}, issn = {0022-1767}, mesh = {*Allergy and Immunology ; Animals ; *Biological Evolution ; Cell Communication ; Central Nervous System/physiology ; Endocrine Glands/physiology ; Hormones/*physiology ; Humans ; Nerve Tissue Proteins/*physiology ; Neurotransmitter Agents/*physiology ; Plant Physiological Phenomena ; Receptors, Cell Surface/*physiology ; Species Specificity ; }, abstract = {Immune function requires intercellular communication. The vocabulary includes messenger molecules closely linked to the immune system as well as more widely acting messengers such as hormones and neuroactive substances. To try to bring these together, we have used an evolutionary approach. Materials that resemble hormonal peptides and neuropeptides, previously thought to be restricted to multicellular animals, are present in protozoa, bacteria, and higher plants. There is also evidence for substances in microbes that bind hormones and other messengers, which resemble receptors of vertebrates. Therefore, we suggest that the molecules of intercellular communication probably arose much earlier in evolution than the endocrine, nervous, and immune systems. This insight provides new understanding of messenger systems in vertebrates, as applied to the immune system, as well as new insights into possible disease mechanisms, including those that involve autoimmunity.}, } @article {pmid3993870, year = {1985}, author = {Podleski, WK}, title = {Cytodestructive mechanisms provoked by food antigens. I. Direct, allergic autocytotoxicity.}, journal = {Allergy}, volume = {40}, number = {3}, pages = {157-165}, doi = {10.1111/j.1398-9995.1985.tb00211.x}, pmid = {3993870}, issn = {0105-4538}, mesh = {Adolescent ; Adult ; Aged ; Allergens/*toxicity ; Animals ; Cattle ; Cell Survival ; Child ; *Cytotoxicity, Immunologic ; Eosinophils/ultrastructure ; Food Hypersensitivity/*immunology ; Humans ; Kinetics ; Leukocyte Count ; Leukocytes/*immunology/physiology ; Middle Aged ; Milk/immunology ; Monocytes/ultrastructure ; Triticum/immunology ; Zea mays/immunology ; }, abstract = {In vitro challenge of peripheral white blood cells (WBC) from 62 food sensitive patients and 22 asymptomatic control individuals was performed using standardized extract of cow milk, corn and wheat. 81% of the patients reacted at least toward one food antigen, showing disintegration of WBC, as measured by trypan blue exclusion technique. The presented experimental condition of the direct binding between food antigen and cell wall membrane suggests that this phenomenon is multicellular in its origin. The interpretation of these studies is of distinct value in directing human food hypersensitivity research in the future.}, } @article {pmid3872630, year = {1985}, author = {Muramatsu, S}, title = {[Antitumor activities in the aspects of evolution and development].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {12}, number = {3 Pt 2}, pages = {720-725}, pmid = {3872630}, issn = {0385-0684}, mesh = {Aging ; Animals ; Biological Evolution ; Cell Division ; Cells, Cultured ; Killer Cells, Natural/*immunology ; Macrophages/*immunology ; Mice ; Neoplasms, Experimental/*immunology/pathology ; T-Lymphocytes/immunology ; }, abstract = {The self-defense mechanism is established on the basis of intrinsic requirements for the formation of multicellular organization and for the maintenance of individuality in each member of a species. Anti-tumor and also anti-parasite mechanisms are therefore included in such intrinsic requirements. In other words, self-defense is one of the concrete manifestations of the self-integrity-maintenance mechanism.}, } @article {pmid3855848, year = {1985}, author = {Carlsson, J and Acker, H}, title = {Influence of the oxygen pressure in the culture medium on the oxygenation of different types of multicellular spheroids.}, journal = {International journal of radiation oncology, biology, physics}, volume = {11}, number = {3}, pages = {535-546}, doi = {10.1016/0360-3016(85)90185-3}, pmid = {3855848}, issn = {0360-3016}, mesh = {Animals ; Cell Line ; Cricetinae ; Cricetulus ; Glioma/pathology ; Humans ; Models, Biological ; Neoplasms/*pathology ; Osteosarcoma/pathology ; *Oxygen ; Partial Pressure ; Thyroid Neoplasms/pathology ; }, abstract = {Six different types of spheroids of both human and rodent origin were cultured, using the liquid-overlay technique. Oxygen gradients were measured with micro-electrodes, when the spheroids were attached to thin cover-glasses. The gradients were measured from the upper surface towards the center of the spheroids. Stable and reproducible gradients were obtained. Large variations were seen in the steepness of the gradients, depending both on the type and on the size of the spheroids. An interesting phenomenon was discovered. When some types of spheroids were cultured in a medium with a low oxygen pressure (medium equilibrated with gas containing 4-5% O2), the gradients continuously changed and became flatter. Detailed studies showed that most of the changes occurred within 2 days after the transfer to the low oxygen pressure. After 2 days, no further dramatic changes took place. This phenomenon was seen in two types of human glioma (U-118 MG and U-178 MG) and two types of embryonic, hamster lung-cell (V-79-379A and CHEL) spheroids. In the cases of human-osteosarcoma (U-393 OS) and human thyroid-cancer (HTh7) spheroids, no such changes could be seen. The low oxygen tension in the culture medium was chosen to mimic the environmental conditions in solid tumors.}, } @article {pmid4088951, year = {1985}, author = {Thompson, SA and Johnson, MP and Heidger, PM and Lubaroff, DM}, title = {Characterization of the heterogeneity of R3327 rat prostatic tumors derived from single-cell clones.}, journal = {The Prostate}, volume = {6}, number = {4}, pages = {369-387}, doi = {10.1002/pros.2990060406}, pmid = {4088951}, issn = {0270-4137}, mesh = {Adenocarcinoma/*pathology/ultrastructure ; Animals ; Cell Transformation, Neoplastic/pathology ; Cells, Cultured ; Clone Cells ; Culture Techniques ; DNA, Neoplasm/analysis ; Flow Cytometry ; Male ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Prostatic Neoplasms/*pathology/ultrastructure ; Rats ; }, abstract = {Prostatic adenocarcinoma is characterized by cellular diversity, which is well demonstrated in the Dunning R3327 rat prostatic adenocarcinoma. This heterogeneity may arise from epigenetic influences, ie, cellular adaptation or selection, and/or from genetic changes. To investigate the question of genetic instability, four tissue culture cell lines were derived from single cells isolated from the uncloned late (UCL) passage of the Dunning R3327H prostate cell culture. Each of these clonally derived tissue cultures was injected into castrated and intact young adult male rats for tumor production. Uncloned early (UCE) and UCL passage tissue cultures were also propagated as solid tumors. Tumors and the cultures from which they were derived were examined for evidence of phenotypic and genetic changes using morphological and cytometric methods. Transmission and scanning electron microscopy revealed only slight differences among the cell cultures. A single population of diploid cells was demonstrated in each of the cell cultures by propidium iodide staining and subsequent flow cytometric measurement of DNA content/nucleus. Tumors of unicellular as well as multicellular origin exhibited extreme heterogeneity of histological features, both among animals as well as within a single tumor. Tumors were surveyed and tissue types were characterized and cataloged. Clone 3 was generally better differentiated than the others; tumors from castrated animals were better differentiated than those from intact animals. Flow cytometry revealed multiple hyperdiploid cell populations that were variable from one sample to another. We concluded that changes in genotype as well as phenotype occurred in the tumors derived from single cells. Some of these changes may have occurred in the cells while still in culture.}, } @article {pmid3933228, year = {1985}, author = {an der Heiden, U and Roth, G and Schwegler, H}, title = {Principles of self-generation and self-maintenance.}, journal = {Acta biotheoretica}, volume = {34}, number = {2-4}, pages = {125-137}, pmid = {3933228}, issn = {0001-5342}, mesh = {Animals ; Environment ; *Models, Biological ; *Reproduction ; Species Specificity ; Time Factors ; }, abstract = {Living systems are characterized as self-generating and self-maintaining systems. This type of characterization allows integration of a wide variety of detailed knowledge in biology. The paper clarifies general notions such as processes, systems, and interactions. Basic properties of self-generating systems, i.e. systems which produce their own parts and hence themselves, are discussed and exemplified. This makes possible a clear distinction between living beings and ordinary machines. Stronger conditions are summarized under the concept of self-maintenance as an almost unique character of living systems. Finally, we discuss the far-reaching consequences that the principles of self-generation and self-maintenance have for the organization, structure, function, and evolution of single- and multi-cellular organisms.}, } @article {pmid3916708, year = {1985}, author = {Ikemura, T}, title = {Codon usage and tRNA content in unicellular and multicellular organisms.}, journal = {Molecular biology and evolution}, volume = {2}, number = {1}, pages = {13-34}, doi = {10.1093/oxfordjournals.molbev.a040335}, pmid = {3916708}, issn = {0737-4038}, mesh = {Animals ; Biological Evolution ; Codon/*genetics ; Escherichia coli/genetics ; RNA, Messenger/*genetics ; RNA, Transfer/*genetics ; Saccharomyces cerevisiae/genetics ; }, abstract = {Choices of synonymous codons in unicellular organisms are here reviewed, and differences in synonymous codon usages between Escherichia coli and the yeast Saccharomyces cerevisiae are attributed to differences in the actual populations of isoaccepting tRNAs. There exists a strong positive correlation between codon usage and tRNA content in both organisms, and the extent of this correlation relates to the protein production levels of individual genes. Codon-choice patterns are believed to have been well conserved during the course of evolution. Examination of silent substitutions and tRNA populations in Enterobacteriaceae revealed that the evolutionary constraint imposed by tRNA content on codon usage decelerated rather than accelerated the silent-substitution rate, at least insofar as pairs of taxonomically related organisms were examined. Codon-choice patterns of multicellular organisms are briefly reviewed, and diversity in G+C percentage at the third position of codons in vertebrate genes--as well as a possible causative factor in the production of this diversity--is discussed.}, } @article {pmid3902346, year = {1985}, author = {Vinogradov, SN}, title = {The structure of invertebrate extracellular hemoglobins (erythrocruorins and chlorocruorins).}, journal = {Comparative biochemistry and physiology. B, Comparative biochemistry}, volume = {82}, number = {1}, pages = {1-15}, doi = {10.1016/0305-0491(85)90120-8}, pmid = {3902346}, issn = {0305-0491}, support = {HL 25952/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Erythrocruorins/genetics/*metabolism ; Extracellular Space/metabolism ; Hemeproteins/genetics/*metabolism ; Hemoglobins/*metabolism ; Invertebrates/*metabolism ; Macromolecular Substances ; Oxygen/metabolism ; *Phylogeny ; Protein Binding ; Species Specificity ; Structure-Activity Relationship ; }, abstract = {The knowledge accumulated over the last 30 years concerning the subunit structures of the invertebrate extracellular hemoglobins permits us to classify them into four distinct groups. Single-domain, single-subunit hemoglobins consisting of single, heme-binding polypeptide chains which have a molecular mass of ca. 16 KDa. These molecules are found in multicellular parasitic organisms such as the trematodes Dicrocoelium and Fasciolopsis and in a few insects, namely in the adult Anisops and in the larvae of Chironomus and of Buenoa. Two-domain, multi-subunit hemoglobins consisting of 30-37 KDa polypeptide chains each containing two, linearly connected heme-binding domains, which form polymeric aggregates with molecular masses ranging from 250 to 800 KDa. These hemoglobins are found extensively among the carapaced branchiopod crustaceans: Caenestheria, Daphnia and Lepidurus hemoglobins have been found to consist of 10, 16 and 24 two-domain chains, respectively. Judging from their electron microscopic appearances, some of the hemoglobins may possess different molecular symmetries. Multi-domain, multi-subunit hemoglobins consisting of two or more polypeptide chains, each comprising many heme-binding domains of ca. 15-20 KDa each. Examples of this class are found among the carapaceless branchiopod crustaceans, the planorbid snails and the clams from the families Astartidae and Carditidae. Artemia hemoglobin consists of two chains of ca. 125 KDa, each containing 8 heme-binding domains. Planorbis and Helisoma hemoglobins possess a molecular mass of ca. 1700 KDa and consist of 10 chains of 170-200 KDa. Astarte and Cardita hemoglobins appear in electron micrographs as rod-like polymers of variable dimensions, 20-30 nm in diameter and 20-100 nm in length and consist of polypeptide chains of ca. 300 KDa. The crustacean and gastropod hemoglobins vary in their electron microscopic appearance and may possess different molecular symmetries. Single-domain, multi-subunit hemoglobins consisting of aggregates of several small subunits, some of which are disulfide-bonded and not all of which contain heme. These molecules are widely distributed among the annelids and possibly also among the pogonophores. They are characterized by a two-tiered, hexagonal electron microscopic appearance, with a vertex-to-vertex diameter of 30 nm and a height of 20 nm, an acidic isoelectric point, a sedimentation coefficient of 50-60 S and a low iron content of 0.24 +/- 0.03%.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid3898274, year = {1985}, author = {Crouse, DA and Turpen, JB and Sharp, JG}, title = {Thymic non-lymphoid cells.}, journal = {Survey of immunologic research}, volume = {4}, number = {2}, pages = {120-134}, pmid = {3898274}, issn = {0252-9564}, support = {AI15819/AI/NIAID NIH HHS/United States ; AM26636/AM/NIADDK NIH HHS/United States ; AM30419/AM/NIADDK NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Endocrine Glands/cytology ; Epithelial Cells ; Humans ; Lymphatic Diseases/pathology ; Species Specificity ; Thymus Gland/*cytology/embryology/immunology ; Vertebrates/anatomy & histology ; }, abstract = {In formulating this summary of our simon-pure knowledge of the structure/function relationships in the thymus, we decided that the time may have come to introduce a suitable dose of cynicism to balance the sometimes hopeless optimism of the past. Are the non-lymphoid cells of the thymus necessary for thymic function? Probably, but not to the extent or uniqueness that some authors including ourselves have previously claimed; T cells can probably differentiate in other tissues but may acquire their preference for MHC class II in the thymus. Mouse thymic lymphoid cell traffic and surface phenotype has recently been summarized pictorally by Scollay and Shortman [95]. Briefly stated, within the thymus, cells are hatched, matched and then dispatched. Minimally, the non-lymphoid cells act either as scenically varied obstacles along the way, nurseries for newborn T cells, or as tombstones for life's disenfranchized, effete and autoaggressive thymocytes. Hassall's corpuscles are morphological structures unique to the thymus, which are most useful to medical students for identification of this tissue. Their function remains one of life's great mysteries. Morphologically, they are suitable companions to the more recently described strange multicellular complexes of lymphocytes and epithelial cells which might be functionally important. The thymus of the much studied inbred, environmentally mollycoddled, laboratory mouse has been often and majestically described. It is probably typical for that of man and most mammals. It may, however, be unrepresentative of the thymus of stressed and parasitized wild animals. Diseases of the thymus generally can be categorized as not having enough thymus, having a neoplastic thymus or having a thymus which does not work properly. The bottom line in our knowledge of thymic nonlymphoid cells is that if you are born without them, you get sick and die; unless, of course, you are a nude mouse in Omaha, in which case you just freeze to death.}, } @article {pmid3893873, year = {1985}, author = {Thompson, SN}, title = {Metabolic integration during the host associations of multicellular animal endoparasites.}, journal = {Comparative biochemistry and physiology. B, Comparative biochemistry}, volume = {81}, number = {1}, pages = {21-42}, doi = {10.1016/0305-0491(85)90157-9}, pmid = {3893873}, issn = {0305-0491}, mesh = {Animals ; Biological Evolution ; *Host-Parasite Interactions ; Humans ; Hymenolepis/metabolism ; Insecta/metabolism ; Larva ; Parasites/immunology/*metabolism ; Parasitic Diseases/immunology/*metabolism ; Schistosoma/metabolism ; Trichinella/metabolism ; Trichinellosis/metabolism ; }, abstract = {The nature of metabolic interaction during parasitic infection was discussed and the concept of metabolic integration outlined. The subjective nature of the integrative argument was noted. The parasite-host relationships of larval trematodes of the genus Schistosoma with their intermediate molluscan hosts, the nematode Trichnella spiralis and cestode Hymenolepis diminuta, with their definitive hosts, as well as the hymenopterous insect parasite, Hyposoter exiguae, with its insect host, Trichoplusia ni, were examined. The significance of the immune system in the establishment of the parasite-host association and the means by which parasites evade host defense were discussed. The involvement of microorganisms or "hyperparasites" during the host associations of multicellular parasites was described. The importance of evolutionary considerations in assessing the nature of metabolic interaction and its significance to the success of the parasite-host relationship was emphasized. The use of teleological assessment and anthropomorphic description was discussed.}, } @article {pmid6493336, year = {1984}, author = {Foster, KW and Saranak, J and Patel, N and Zarilli, G and Okabe, M and Kline, T and Nakanishi, K}, title = {A rhodopsin is the functional photoreceptor for phototaxis in the unicellular eukaryote Chlamydomonas.}, journal = {Nature}, volume = {311}, number = {5988}, pages = {756-759}, doi = {10.1038/311756a0}, pmid = {6493336}, issn = {0028-0836}, support = {EY 01253/EY/NEI NIH HHS/United States ; EY 03760/EY/NEI NIH HHS/United States ; }, mesh = {Cell Movement ; Chlamydomonas/*physiology ; Light ; Photoreceptor Cells/*physiology ; Retinal Pigments/*physiology ; Retinaldehyde/physiology ; Rhodopsin/*physiology ; Spectrophotometry ; }, abstract = {Rhodopsin is a visual pigment ubiquitous in multicellular animals. If visual pigments have a common ancient origin, as is believed, then some unicellular organisms might also use a rhodopsin photoreceptor. We show here that the unicellular alga Chlamydomonas does indeed use a rhodopsin photoreceptor. We incorporated analogues of its retinal chromophore into a blind mutant; normal photobehaviour was restored and the colour of maximum sensitivity was shifted in a manner consistent with the nature of the retinal analogue added. The data suggest that 11-cis-retinal is the natural chromophore and that the protein environment of this retinal is similar to that found in bovine rhodopsin, suggesting homology with the rhodopsins of higher organisms. This is the first demonstration of a rhodopsin photoreceptor in an alga or eukaryotic protist and also the first report of behavioural spectral shifts caused by exogenous synthetic retinals in a eukaryote. A survey of the morphology and action spectra of other protists suggests that rhodopsins may be common photoreceptors of chlorophycean, prasinophycean and dinophycean algae. Thus, Chlamydomonas represents a useful new model for studying photoreceptor cells.}, } @article {pmid6207454, year = {1984}, author = {Liwnicz, BH and Liwnicz, RG and Huff, JS and McBride, BH and Tew, JM}, title = {Giant granular cell tumor of the suprasellar area: immunocytochemical and electron microscopic studies.}, journal = {Neurosurgery}, volume = {15}, number = {2}, pages = {246-251}, doi = {10.1227/00006123-198408000-00017}, pmid = {6207454}, issn = {0148-396X}, mesh = {Adult ; Brain Neoplasms/*analysis/ultrastructure ; Cytoplasmic Granules/analysis ; Cytoskeleton/ultrastructure ; Female ; Giant Cell Tumors/*analysis/ultrastructure ; Glial Fibrillary Acidic Protein/analysis ; Humans ; Lysosomes/analysis/ultrastructure ; Male ; Microscopy, Electron ; S100 Proteins/analysis ; Staining and Labeling ; }, abstract = {We describe a case of a granular cell tumor (GCT) of the suprasellar region with an 11-year history in a 26-year-old woman. The computed tomographic scan showed a midline, contrast-enhancing, noncalcified mass. The biopsy was diagnosed as GCT. The tumor was treated with radiation therapy. At necropsy, a large, homogeneous GCT surrounded by gliosis was found. The tumor cells were filled with granules positive for periodic acid-Schiff, diastase-resistant. The cells did not contain glial fibrillary acidic protein or S-100 protein. Electron microscopy showed tumor cells filled with innumerable lysosomal structures. No intermediate filament was found within the cytoplasm. The tumor cells were not surrounded by a basement membrane. Based on this study and on our review of the literature, the suggestion that GCT has a multicellular origin is upheld.}, } @article {pmid6474128, year = {1984}, author = {Berthoud, S}, title = {[Eosinophilia and dormant parasitosis].}, journal = {Schweizerische medizinische Wochenschrift}, volume = {114}, number = {29}, pages = {1025-1029}, pmid = {6474128}, issn = {0036-7672}, mesh = {Amebiasis/blood ; Eosinophilia/*parasitology ; Humans ; Malaria/blood ; Parasitic Diseases/*blood/complications/diagnosis ; Schistosomiasis/blood ; }, abstract = {The exotic diseases are still far from a daily preoccupation and sometimes face the physician with unusual problems. Two classical situations are reported: eosinophilia of parasitic origin, and three examples of asymptomatic parasitosis. Eosinophilia is a classical sign accompanying multicellular parasites (helminths). The rate depends on the duration of the disease, the type of parasite and the scale of the infestation. Pathological eosinophilia is usually present before diagnosis is possible; hence it is necessary to repeat laboratory examinations. Several parasitic diseases are asymptomatic and, after a long evolution, cause serious complications. Examples quoted are malaria, for which there is no absolute prophylaxis, amoebiasis, which is responsible for hepatic necrosis in patients who have never had dysentery, and schistosomiasis, which insidiously causes irreversible hepatic necrosis and ureteral stenosis. These conditions are becoming increasingly frequent in our countries and call for closer attention.}, } @article {pmid6539911, year = {1984}, author = {Ohama, T and Kumazaki, T and Hori, H and Osawa, S}, title = {Evolution of multicellular animals as deduced from 5S rRNA sequences: a possible early emergence of the Mesozoa.}, journal = {Nucleic acids research}, volume = {12}, number = {12}, pages = {5101-5108}, pmid = {6539911}, issn = {0305-1048}, mesh = {Animals ; Base Sequence ; *Biological Evolution ; Invertebrates/*genetics ; Molecular Weight ; Octopodiformes/genetics ; Phylogeny ; RNA, Ribosomal/*genetics ; Species Specificity ; }, abstract = {The nucleotide sequences of 5S rRNA from a mesozoan Dicyema misakiense and three metazoan species, i.e., an acorn-worm Saccoglossus kowalevskii, a moss-animal Bugula neritina, and an octopus Octopus vulgaris have been determined. A phylogenic tree of multicellular animals has been constructed from 73 5S rRNA sequences available at present including those from the above four sequences. The tree suggests that the mesozoan is the most ancient multicellular animal identified so far, its emergence time being almost the same as that of flagellated or ciliated protozoans. The branching points of planarians and nematodes are a little later than that of the mesozoan but are clearly earlier than other metazoan groups including sponges and jellyfishes. Many metazoan groups seem to have diverged within a relatively short period.}, } @article {pmid6736343, year = {1984}, author = {Moulton-Levy, P and Jackson, CE and Levy, HG and Fialkow, PJ}, title = {Multiple cell origin of traumatically induced keloids.}, journal = {Journal of the American Academy of Dermatology}, volume = {10}, number = {6}, pages = {986-988}, doi = {10.1016/s0190-9622(84)80319-9}, pmid = {6736343}, issn = {0190-9622}, support = {CA16448/CA/NCI NIH HHS/United States ; CA22595/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Blood Cells/enzymology ; Cell Division ; Female ; Fibroblasts/enzymology ; Glucosephosphate Dehydrogenase/*genetics ; Humans ; Isoenzymes/*genetics ; Keloid/*enzymology/genetics/pathology ; Skin/pathology ; }, abstract = {Six keloids from five patients heterozygous for the X-linked glucose-6-phosphate dehydrogenase (G6PD) locus were studied. Both the B and A enzymes were found in the keloids in similar proportions to the normal tissues. This finding indicates that keloids have a multicellular origin and that they do not develop clonally as do most neoplasms.}, } @article {pmid6331180, year = {1984}, author = {Bellman, KL and Goldberg, LJ}, title = {Common origin of linguistic and movement abilities.}, journal = {The American journal of physiology}, volume = {246}, number = {6 Pt 2}, pages = {R915-21}, doi = {10.1152/ajpregu.1984.246.6.R915}, pmid = {6331180}, issn = {0002-9513}, mesh = {Animals ; Brain/*physiology ; Cyclic AMP/metabolism ; Dictyostelium/physiology ; Escherichia coli/physiology ; Humans ; *Language ; *Linguistics ; Models, Psychological ; *Motor Activity ; *Movement ; Species Specificity ; }, abstract = {We start with the view that the development of systems of symbols is rooted in the regulation of cellular processes and the behavior of unicellular animals. Animals would thereafter start to externalize these internal symbol systems, to coordinate movements with each other. We propose that the brains of multicellular animals can be understood as a continuing elaboration of the early chemical symbol systems of unicellular animals: the labile symbols of the unicellular animal are replaced by hormones, more stable chemical compounds, and nerves that are seen as more stable and more specific routes of activation; and brains developed layers of symbols such that the domain of a symbol is not a set of bodily processes but rather a set of brain processes. Human language is very much in the "style" of the rule-governed symbol manipulation required by all behaving animals, although unique in its complexity. We suggest that the essential question is not how humans have evolved symbolic and linguistic abilities from a primitive sensorimotor brain but rather how do symbols come to exist in biological systems and what is useful and necessary about a system of symbols for the coordination of action within animals and among animals.}, } @article {pmid6722041, year = {1984}, author = {Powell, JS and Fialkow, PJ and Adamson, JW}, title = {Human mixed cell colonies: unicellular or multicellular origin--analysis by G-6-PD.}, journal = {British journal of haematology}, volume = {57}, number = {1}, pages = {89-95}, pmid = {6722041}, issn = {0007-1048}, support = {AM-19410/AM/NIADDK NIH HHS/United States ; CA 16448/CA/NCI NIH HHS/United States ; CA 31615/CA/NCI NIH HHS/United States ; }, mesh = {Bone Marrow Cells ; Cell Count ; Cell Differentiation ; Cells, Cultured ; Clone Cells/cytology ; Female ; Glucosephosphate Dehydrogenase/*analysis ; Hematopoiesis ; Hematopoietic Stem Cells/*cytology/enzymology ; Humans ; }, abstract = {Marrow and peripheral blood cells from normal women heterozygous (GdB/GdA) at the X-chromosome-linked glucose-6-phosphate dehydrogenase (G-6-PD) locus were cultured at cell concentrations ranging from 2 X 10(4)/ml to 4 X 10(5)/ml to test formally the plating conditions necessary for reliable enumeration of multipotent stem cells (CFU-mix). The culture system was rigorously tested by plating cells obtained after velocity sedimentation and the G-6-PD enzyme type of individual colonies was determined. At cell concentrations less than or equal to 7.5 X 10(4)/ml for marrow and less than or equal to 1 X 25 X 10(5)/ml for peripheral blood, mixed-cell colonies had either type A or type B enzyme, but not both. At higher cell concentrations, significant numbers of colonies showed both enzyme types and therefore arose from more than one cell. These studies demonstrate that enumeration of CFU-mix by in vitro colony assay is accurate only at low cell concentrations. Studies of haematopoietic differentiation relying on in vitro colony assays of multipotent stem cells must be carefully analysed in light of these data.}, } @article {pmid6462202, year = {1984}, author = {Anders, F and Schartl, M and Barnekow, A}, title = {Xiphophorus as an in vivo model for studies on oncogenes.}, journal = {National Cancer Institute monograph}, volume = {65}, number = {}, pages = {97-109}, pmid = {6462202}, issn = {0083-1921}, mesh = {Animals ; Fishes/classification/embryology/*genetics ; Genes, Regulator ; Melanoma/genetics ; Neoplasms, Experimental/chemically induced/genetics ; *Oncogenes ; Pigments, Biological ; }, abstract = {The capacity of Xiphophorus to develop neoplasia can be formally assigned to a "tumor gene" (Tu), which appears to be a normal part of the genome of all individuals. The wild fish have evolved population-specific and cell type-specific systems of regulatory genes (R) for Tu that protect the fish from neoplasia. Hybridization of members of different wild populations in the laboratory followed by treatment of the hybrids with carcinogens led to disintegration of the R systems permitting excessive expression of Tu and thus resulting in neoplasia. Certain hybrids developed neoplasia even spontaneously. Observations on the genuine phenotypic effect of the derepressed Tu in the early embryo indicated an essential normal function of this oncogene in cell differentiation, proliferation and cell-cell communication. Tu appeared to be indispensable in the genome but may also be present in accessory copies. Recently, c-src, the cellular homolog of the Rous sarcoma virus oncogene v-src, was detected in Xiphophorus. The protein product of c-src, pp60c-src, was identified and then examined by its associated kinase activity. This pp60c-src was found in all individuals tested, but, depending on the genotype, its kinase activity was different. The genetic characters of c-src, such as linkage relations, dosage relations, expression, etc., correspond to those of Tu. From a systematic study which showed that pp60c-src was present in all metazoa tested ranging from mammals down to sponges, we concluded that c-src has evolved with the multicellular organization of animals. Neoplasia of animals and humans is a characteristic closely related to this evolution. Our data showed that small aquarium fish, besides being used successfully because they are time-, space-, and money-saving systems for carcinogenicity testing, are also highly suitable for basic studies on neoplasia at the populational, morphological, developmental, cell biological, and molecular levels.}, } @article {pmid6391907, year = {1984}, author = {Golubev, AG}, title = {[Carcinogenesis, embryogenesis and aging from the view point of the assessment of cell proliferation and differentiation as a stochastic process].}, journal = {Eksperimental'naia onkologiia}, volume = {6}, number = {5}, pages = {10-15}, pmid = {6391907}, issn = {0204-3564}, mesh = {*Aging ; Animals ; Cell Cycle ; *Cell Differentiation ; *Cell Division ; Cell Survival ; *Cell Transformation, Neoplastic ; Embryo, Mammalian/*physiology ; Gene Expression Regulation ; Humans ; Models, Biological ; *Probability ; *Stochastic Processes ; }, abstract = {An approach to cell proliferation and differentiation as to stochastic processes is described. The rate constants of cell population transitions to subsequent epigenetic states are interpreted as indicating instability of initial states. The duration of embryogenesis, the rate of loss of the ability to proliferation (a result of final differentiation) by the initial cell cultures, the error accumulation rate in the genetic cell apparatus (including both the genome itself and its interactions with the chromatin components) which determines the rate of ageing and the rate of the tumour incidence rise in particular, are all connected via the level of instability of the epigenetic states of cells. It is supposed that the differentiation mechanism of multicellular organisms originated from mechanisms of intragenome recombinational rearrangements of unicellular ones. A hypothetic scheme for basic processes occurring during cell differentiation is proposed accounting for the dual character of oncogenes necessary for differentiation but able to block it under definite conditions.}, } @article {pmid6669093, year = {1983}, author = {Holt, JA}, title = {The fundamental chemistry of life. An attempt to define and identify the basic reaction responsible for life's creation and evolution.}, journal = {Medical hypotheses}, volume = {12}, number = {4}, pages = {359-367}, doi = {10.1016/0306-9877(83)90107-x}, pmid = {6669093}, issn = {0306-9877}, mesh = {*Biological Evolution ; Glycolysis ; Growth ; Neoplasms/etiology ; *Origin of Life ; }, abstract = {All natural growth follows exponential characteristics which vary from a simple exponential equation (non-solid cancer, bacteria) to complex Gompertzian functions describing solid cancer and multicellular organisms. Like all chemical processes the reagents (energy sources of food) react during life to produce vital energy, but in addition also create the next generation of life. This latter reaction is unique in that a simple proportional increase in the reagents creates an exponential increase in products: it is the sole invariable criterion of all life. The target of combined ionising and non-ionising radiations in cancer cells appears to be identical with this fundamental exponential chemical reaction. Identification of this target as a system of anaerobic glycolysis suggests that life's first reaction is a unique one whereby a simple proportional increase in available glucose causes an exponential proportional increase in energy which is available solely for reproduction.}, } @article {pmid6640546, year = {1983}, author = {Hard, GC and Mackay, RL and Martin, JT and Inoue, K}, title = {Differentiated features of a transformed epithelial cell line (TRKE-1) derived from dimethylnitrosamine-treated rat kidney.}, journal = {Cancer research}, volume = {43}, number = {12 Pt 1}, pages = {6045-6056}, pmid = {6640546}, issn = {0008-5472}, support = {CA-12227/CA/NCI NIH HHS/United States ; CA-24216/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/drug effects ; Cell Line ; *Cell Transformation, Neoplastic ; Clone Cells ; Dimethylnitrosamine/*toxicity ; Epithelium/drug effects/physiology/ultrastructure ; Kidney/*physiopathology ; Kinetics ; Microscopy, Electron ; Rats ; }, abstract = {TRKE-1 is a pure line of epithelium-like neoplastic cells derived from the kidney of a rat treated 48 hr previously with a carcinogenic dose of dimethylnitrosamine. Using light microscopy, the line was characterized by cohesive growth behavior typical for epithelium and the formation of hemicysts (domes) at postconfluence. Enhancement of dome formation by dibutyryl cyclic adenosine 3':5'-monophosphate and dimethyl sulfoxide and inhibition by ouabain established these structures as a manifestation of differentiated cellular function, namely, transepithelial fluid transport. Structurally, TRKE-1 cells in monolayer culture were characterized by apical distribution of microvilli, cilia, and endocytic vesicles, ordered sequence of junctional components at the apical lateral border including tight junction and desmosomes, basolateral cellular interdigitations below the junctional complex, basal location of microfilament bundles, and a conspicuous content of mitochondria. Each of these features typifies mammalian renal tubule epithelium in vivo. The occasional profusion of microvilli; the prominent, apically distributed endocytic vesicles; and the well-developed basal microfilament tracts suggest, in particular, that the proximal segment of the nephron may represent the site of origin of this transformed cell line. The various morphological aspects of renal epithelial differentiation were also expressed in multicellular tumor spheroids grown in suspension, with an accentuation of junctional complexes, endocytic vesicles, and intracytoplasmic lumina. In addition, this three-dimensional culture mode supported cellular organization into acinar profiles suggestive of primitive tubule formation. In confirming the epithelial nature of TRKE-1 and a possible identity with the proximal tubule, this study provides an in vitro animal model representative of chemically transformed renal epithelium which may be analogous to human renal cell carcinoma.}, } @article {pmid6852971, year = {1983}, author = {Carlsson, J and Nilsson, K and Westermark, B and Pontén, J and Sundström, C and Larsson, E and Bergh, J and Påhlman, S and Busch, C and Collins, VP}, title = {Formation and growth of multicellular spheroids of human origin.}, journal = {International journal of cancer}, volume = {31}, number = {5}, pages = {523-533}, doi = {10.1002/ijc.2910310502}, pmid = {6852971}, issn = {0020-7136}, mesh = {Cell Aggregation ; Cell Line ; Culture Media ; Humans ; Neoplasms/*pathology ; Ploidies ; }, abstract = {Different types of human cells which normally grow as monolayers or suspension cultures were tested for their capacity to form and grow as spheroids. Sixteen out of the 27 tested tumour cell lines formed spheroids. Nearly all of these spheroids also grew. With only two exceptions the doubling times were longer when the tumour cells grew as spheroids than when they grew in conventional mass culture. Eleven out of 13 tested human non-tumour cells formed small spheroids but of these only the spheroids of lymphoid origin could grow. These lymphoid cells grew faster when aggregated to spheroids than when in single-cell suspension culture. None of the other non-tumour cells, which normally grew as monolayers, could grow as spheroids. The normally monolayer-cultured tumour cells formed symmetrical spheroids with smooth surfaces while the normally suspension-cultured cells formed irregular spheroids with rough surfaces. All large spheroids had a necrotic centre surrounded by a shell of viable cells. The thickness of the viable cell layer varied depending on cell type. The shape and organization of cells within the spheroids also varied largely. The results show that many types of human cells can be cultured as spheroids and that a wide spectrum of morphological appearances and growth rates can be obtained.}, } @article {pmid6187443, year = {1983}, author = {Medina, D and Miller, F and Oborn, CJ and Asch, BB}, title = {Mitochondrial inclusions in selenium-treated mouse mammary epithelial cell lines.}, journal = {Cancer research}, volume = {43}, number = {5}, pages = {2100-2105}, pmid = {6187443}, issn = {0008-5472}, support = {CA-11944/CA/NCI NIH HHS/United States ; CA-31755/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Cytoskeleton/ultrastructure ; Epithelium/drug effects/metabolism/ultrastructure ; Fluorescent Antibody Technique ; Inclusion Bodies/ultrastructure ; Keratins/metabolism ; Mammary Glands, Animal/*drug effects/metabolism/ultrastructure ; Mice ; Microscopy, Electron ; Microtubules/ultrastructure ; Mitochondria/ultrastructure ; Selenium/*pharmacology ; }, abstract = {The effects of selenium on three mammary epithelial cell lines (YN-4, WAZ-2t, and CL-S1) grown in vitro were examined by immunocytochemical and transmission electron microscopy technique. The primary effect of selenium at the ultrastructural level was the appearance of electron-dense inclusions within the mitochondrial matrix. The mitochondrial inclusions were seen in all three cell lines, although most readily induced in YN-4 cells, the cell line which is most sensitive to selenium-mediated growth inhibition. Selenium at 5 x 10(-8) and 5 x 10(-6) M did not alter cytoplasmic microtubules or intermediate filament networks, as determined by immunocytochemical staining. Immunocytochemical staining for cytoplasmic filaments and microtubules, and transmission electron microscopy observations, supported the contention that cells from all three cell lines were epithelial in origin, since they contained abundant desmosomes and were uniformly positive for keratin intermediate filaments. Whereas line YN-4 was negative for vimentin intermediate filaments, a minority (5 to 24%) of the cells in lines CL-S1 and WAZ-2t stained positively. In addition, the tumorigenicity of these three cell lines was assessed by in vitro growth assays and in vivo transplantation assays. Cell lines YN-4 and WAZ-2t, but not line CL-S1, were tumorigenic in syngeneic mice. All tumors were mammary adenocarcinomas. Cytochalasin B-induced multinucleation assay and growth as multicellular spheroides correlated positively with in vivo tumorigenicity, whereas saturation density and growth in low Ca2+ medium were not correlated with tumorigenicity. It is speculated that one of the early effects of selenium-mediated growth inhibition may be a modulation of mitochondrial function.}, } @article {pmid6300500, year = {1983}, author = {Collins, SJ and Fialkow, PJ}, title = {Clonal nature of mink cell focus-inducing virus-induced AKR leukemia: studies with X-chromosome inactivation cellular mosaicism.}, journal = {Journal of the National Cancer Institute}, volume = {70}, number = {3}, pages = {529-533}, pmid = {6300500}, issn = {0027-8874}, support = {GM-15253/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Clone Cells ; Electrophoresis, Starch Gel ; Female ; Genetic Markers ; Leukemia Virus, Murine ; Leukemia, Experimental/enzymology/*etiology ; Male ; Mice ; Mice, Inbred AKR/genetics ; *Mosaicism ; Phenotype ; Phosphoglycerate Kinase/analysis/*genetics ; Thymoma/enzymology/*etiology ; *Tumor Virus Infections ; X Chromosome ; }, abstract = {The number of cells from which murine thymic leukemias (thymomas) develop after neonatal injection with a mink cell focus-inducing recombinant virus was studied in AKR mice heterozygous at the X-linked phosphoglycerate kinase (PGK) locus. Because only one of the two X-chromosomes is active in XX somatic cells, thymic leukemias that are clonal should display either type A or type B PGK but not both, whereas those with a multicellular origin may exhibit both enzymes. In 23 of 25 animals studied, thymomas expressed exclusively (11 animals) or predominantly (12 animals) a single enzyme in contrast to normal tissue which expressed both enzyme types in approximately equal ratios. In the 12 thymomas expressing a minor enzyme component, the predominant enzyme in the original tumor always predominated in the thymomas arising in animals transplanted with the original tumors, indicating that this minor PGK component was not contributed by malignant cells. The results indicate that the great majority of recombinant virus-induced AKR leukemias are clonal.}, } @article {pmid6655700, year = {1983}, author = {Kumazaki, T and Hori, H and Osawa, S}, title = {Phylogeny of protozoa deduced from 5S rRNA sequences.}, journal = {Journal of molecular evolution}, volume = {19}, number = {6}, pages = {411-419}, pmid = {6655700}, issn = {0022-2844}, mesh = {Animals ; *Base Sequence ; Chlamydomonas/genetics ; Eukaryota/*genetics ; Nucleic Acid Conformation ; *Phylogeny ; RNA, Ribosomal/*genetics ; Species Specificity ; }, abstract = {The nucleotide sequences of 5S rRNAs from three protozoa, Bresslaua vorax, Euplotes woodruffi and Chlamydomonas sp. have been determined and aligned together with the sequences of 12 protozoa species including unicellular green algae already reported by the authors and others. Using this alignment, a phylogenic tree of the 15 species of protozoa has been constructed. The tree suggests that the ancestor for protozoa evolved at an early time of eukaryotic evolution giving two major groups of organisms. One group, which shares a common ancestor with vascular plants, contains a unicellular green flagellate (Chlamydomonas) and unicellular green algae. The other group, which shares a common ancestor with the multicellular animals, includes various flagellated protozoa (including Euglena), ciliated protozoa and slime molds. Most of these protozoa appear to have separated from one another at a fairly early period of eukaryotic evolution.}, } @article {pmid6382521, year = {1983}, author = {Fidler, IJ}, title = {The Ernst W. Bertner Memorial Award lecture: the evolution of biological heterogeneity in metastatic neoplasms.}, journal = {Symposium on Fundamental Cancer Research}, volume = {36}, number = {}, pages = {5-26}, pmid = {6382521}, issn = {0190-1214}, support = {N01-CO-23909/CO/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Division ; Cell Line ; Cells, Cultured ; Clone Cells ; Humans ; Mice ; *Neoplasm Invasiveness ; Neoplasm Metastasis/*pathology ; Neoplasm Transplantation ; Neoplasms/*pathology ; Neoplastic Stem Cells/pathology ; Organ Specificity ; Phenotype ; }, abstract = {The complexity of the processes of tumor progression and metastasis makes it difficult to provide generalized rules. Results and hypotheses that are based upon a single tumor system or a simple experimental technique are likely to be revised as more data become available. However, bearing these limitations in mind and ignoring the above warnings, I wish to conclude the following: By the time of diagnosis, many malignant neoplasms are heterogeneous, i.e., they contain subpopulations of cells with different biological characteristics. The process of metastasis involves a sequence of complex events whose outcome depends on tumor cell properties and host factors. The metastatic process selects variants from a heterogeneous starting population. The diversity for the metastatic phenotype may be a consequence of the multicellular origin of a neoplasm or it may be the result of continuous evolution and progression in tumors of unicellular origin. Metastatic clones appear, in general, to be less stable than nonmetastatic clones. Metastatic clones exhibit an increased rate of spontaneous mutation compared with nonmetastatic clones. Some metastases may be clonal in their origin, and multiple metastases can originate from different progenitor cells. Biological diversity can rapidly develop within individual metastases. The acquisition of phenotypic heterogeneity by populations of tumor cells imposes a degree of stability on the tumor as a whole. The generation of biological diversity in malignant neoplasms and within and among metastases has profound implications both for studies on the pathogenesis of cancer metastasis and for the design of any successful approach to the treatment of this disease.}, } @article {pmid6362975, year = {1983}, author = {Akiyama, SK and Johnson, MD}, title = {Fibronectin in evolution: presence in invertebrates and isolation from Microciona prolifera.}, journal = {Comparative biochemistry and physiology. B, Comparative biochemistry}, volume = {76}, number = {4}, pages = {687-694}, doi = {10.1016/0305-0491(83)90378-4}, pmid = {6362975}, issn = {0305-0491}, mesh = {Animals ; *Biological Evolution ; Fibronectins/*analysis/metabolism ; Fluorescent Antibody Technique ; Porifera/*analysis ; Radioimmunoassay ; Tissue Distribution ; }, abstract = {Fibronectin is found in the tissues of a series of vertebrates and invertebrates which suggests its appearance with the simplest multicellular organisms. Fibronectin is specifically localized on the surface and on the substrate in the immediate vicinity of some, but not all, dissociated Microciona prolifera cells, suggesting that the expression of fibronectin in this organism might be dependent on cell type and/or developmental stage. Fibronectin has been partially purified and characterized from intact Microciona prolifera tissue on the basis of its immunological and biochemical properties.}, } @article {pmid6891260, year = {1982}, author = {Jones, AC and Stratford, IJ and Wilson, PA and Peckham, MJ}, title = {In vitro cytotoxic drug sensitivity testing of human tumour xenografts grown as multicellular tumour spheroids.}, journal = {British journal of cancer}, volume = {46}, number = {6}, pages = {870-879}, pmid = {6891260}, issn = {0007-0920}, support = {G0500366/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Breast Neoplasms/pathology ; Cell Aggregation/drug effects ; Cell Division/drug effects ; Cell Line ; Cisplatin/pharmacology ; Dose-Response Relationship, Drug ; Doxorubicin/pharmacology ; Female ; Humans ; Lomustine/pharmacology ; Lung Neoplasms/pathology ; Melphalan/pharmacology ; Mice ; Neoplasm Transplantation ; Neoplasms/*pathology ; Ovarian Neoplasms/pathology ; Transplantation, Heterologous ; Vinca Alkaloids/pharmacology ; }, abstract = {Tumour cells from 7 patients with ovarian carcinoma and from 22 different human tumour xenografts representing a wide range of histological sub-types have been examined for multicellular spheroid forming ability. Spheroid formation was limited to cells derived from xenografts. Of the 22 lines tested, 5 formed spheroids capable of growth in isolation. There was no clear relationship between histological type and spheroid-forming ability. The plating efficiency of tumour cells obtained from spheroids was always greater than for the cells obtained from the dissociated tumour of origin and was in some cases as much as 6-fold greater. Spheroid growth was nearly exponential for 4 cell lines. Volume growth delay was used to investigate the activity of melphalan, adriamycin, the Vinca alkaloids, CCNU and cisplatin. Differences between lines in drug response broadly reflected patient and in vivo xenograft response.}, } @article {pmid6760500, year = {1982}, author = {Polunovskiĭ, VA}, title = {[Genetic control of cell proliferation and the evolution of the cell cycle].}, journal = {Tsitologiia}, volume = {24}, number = {12}, pages = {1379-1392}, pmid = {6760500}, issn = {0041-3771}, mesh = {Animals ; Biological Evolution ; *Cell Cycle ; *Cell Division ; Cell Fusion ; Cytogenetics ; Eukaryotic Cells/cytology ; Genes ; Interphase ; Mutation ; Time Factors ; }, abstract = {The characteristics of temperature-sensitive cell cycle mutants along with cell fusion studies suggest that gene-dependent synthesis of the inducers of DNA replication is submitted to negative control via an endogenous inhibitor. The dependence of metazoan cell proliferation on extracellular stimulators (hormones, serum factors etc.) appears to be determined by these inhibitors. By contrast, prokaryotic cells and eukaryotic unicellular organisms seem to synthesize the inducers of DNA replication constitutively which enables these cells to proliferate with no specific stimulators. Thus, the following types of the cell cycle may exist in living organisms: A--prokaryotic type of cell cycle where DNA can be synthesized continuously under conditions of nutrient abundance; B--primitive eukaryotic type where DNA replication is interrupted by the condensation of chromosomes prior to mitosis; C--metazoan eukaryotic cell cycle of a higher order where cells after mitosis pass into a resting state, under the influence of endogenous inhibitors and resume the proliferation in a stochastic manner under the effect of exogenous activators. The alternation of active proliferation and resting in the cell life cycle is a necessary prerequisite for cell specialization and population-size control. The essential feature of evolutionary cell cycle reorganization is a substitution of the unlimited primitive cell multiplication with eukaryotic organization of genome and specific cell functions in the multicellular organism.}, } @article {pmid7135207, year = {1982}, author = {Jackson, CE and Cerny, JC and Block, MA and Fialkow, PJ}, title = {Probable clonal origin of aldosteronomas versus multicellular origin of parathyroid "adenomas".}, journal = {Surgery}, volume = {92}, number = {5}, pages = {875-879}, pmid = {7135207}, issn = {0039-6060}, support = {AM10206/AM/NIADDK NIH HHS/United States ; CA 16448/CA/NCI NIH HHS/United States ; CA 22595/CA/NCI NIH HHS/United States ; }, mesh = {Adenoma/*pathology ; Adrenal Cortex Neoplasms/genetics/metabolism/*pathology ; Adult ; Aldosterone/*metabolism ; Female ; Genetic Linkage ; Glucosephosphate Dehydrogenase/genetics ; Heterozygote ; Humans ; Hyperaldosteronism/etiology ; Isoenzymes/genetics ; Middle Aged ; Parathyroid Neoplasms/*pathology ; Pedigree ; X Chromosome ; }, abstract = {Adrenocortical adenomas causing hyperaldosteronism in two women heterozygous at the X chromosome-linked glucose-6-phosphate dehydrogenase (G-6-PD) locus exhibited only one G-6-PD isoenzyme. This finding suggests a clonal development for these benign tumors and contrasts with the multicellular origin of parathyroid adenomas reported in three patients from our institution in 1977 and found subsequently in seven other hyperparathyroid women whose cases are reported here. One of these seven patients had hereditary hyperparathyroidism. In this case each of three glands removed showed both A and B G-6-PD isoenzymes in similar ratios as were found in normal tissues. The multicellular origin of hereditary hyperparathyroidism is compatible with the concept of parathyroid lesions being manifestations of the first genetic event in Knudson's two-mutational-event theory for the initiation of cancer. The multicellular origin of sporadic parathyroid tumors suggest that they are caused by some factors stimulating many cells in the parathyroid glands. The young average age of onset of eight cases of parathyroid cancer from five families with hereditary hyperparathyroidism in the literature is also compatible with Knudson's theory. G-6-PD studies of other aldosteronomas, parathyroid tumors, and other endocrine neoplasms may provide important information about the pathogenesis of these conditions.}, } @article {pmid7112116, year = {1982}, author = {Fidler, IJ and Hart, IR}, title = {Biological diversity in metastatic neoplasms: origins and implications.}, journal = {Science (New York, N.Y.)}, volume = {217}, number = {4564}, pages = {998-1003}, doi = {10.1126/science.7112116}, pmid = {7112116}, issn = {0036-8075}, support = {N01-CO-75380/CO/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Cell Transformation, Neoplastic/pathology ; Clone Cells ; Humans ; Immunity ; Melanoma/genetics/pathology ; Mice ; Mice, Inbred Strains ; Mutation ; Neoplasm Metastasis/*pathology ; Neoplasms, Experimental/pathology ; Phenotype ; Skin Neoplasms/genetics/pathology ; }, abstract = {Whether neoplasms are unicellular or multicellular in their origin, the process of tumor evolution and progression can rapidly generate biological diversity. Metastases result from the survival and proliferation of specialized subpopulations of cells within the parent tumor. Metastases may have a clonal origin and different metastases may develop from different progenitor cells. However, as with the primary tumor, the origin of metastases is unimportant since the process of tumor evolution and progression can generate biological diversity within and among different metastatic foci.}, } @article {pmid7162802, year = {1982}, author = {Oró, J and Rewers, K and Odom, D}, title = {Criteria for the emergence and evolution of life in the solar system.}, journal = {Origins of life}, volume = {12}, number = {3}, pages = {285-305}, pmid = {7162802}, issn = {0302-1688}, mesh = {*Biological Evolution ; Chemical Phenomena ; Chemistry ; *Extraterrestrial Environment ; Origin of Life ; *Space Flight ; }, abstract = {During the past years we have explored most of the bodies of the solar system by means of the Apollo, Venera, Viking, Voyager, and other space missions. We are now in a better position to be able to compare the conditions of other planets and satellites with those of the Earth in order to determine what is unique about our planet which permitted the emergence and evolution of life on it. On the basis of this and other available scientific information we have arrived at the conclusion that there are at least some twentyfive specific conditions or requirements which have to be fulfilled in order for life as we know it to appear and evolve in a planetary system such as ours. Most of these necessary conditions or requirements are mutually interdependent, but in order to discuss their role in depth they have been divided into five major general areas which are discussed in some detail herein. Planetary criteria, which relate to the physical properties of the planet as it is formed and as it becomes a differentiated cosmic body and potential abode of life. The mass, orbital characteristics and energetic relationships with the central star as well as the discrete separation of gas, liquid and solid phases of the planet are of utmost importance. Chemical criteria, which are concerned with the composition, availability of effective energy sources, and chemical constraints (solvent, pH range, redox potential) of the environment(s) where reactions take place for the prebiological formation of biochemical compounds. Protobiological criteria, which relate to the prebiologically synthesized oligomeric and polymeric biomolecules, how they interact cooperatively to form protobiological structures and functions (replication, catalysis, information transfer, etc.) and self-assemble to give rise to a living system. Evolutionary criteria, which are concerned with the processes responsible for the increase in complexity of organisms by genomic multiplication, symbiotic integration and cellular differentiation, as well as with the negentropic ability of organisms to continuously recycle all the volatile biogenic elements. Altogether these processes made possible the development and evolution of life from the simplest prokaryotic cell ancestor to a cognitive and manipulative multicellular organism (man). In order to extend this inquiry to other systems beyond our solar system a fifth set of requirements based on astronomical observations is also discussed, namely, the Stellar criteria, which relate to the elemental composition mass, lifetime, and other features of Main Sequence stars which may be surrounded by planetary systems similar to our own. Finally, a brief review is made on the probability of the existence of extraterrestrial life as well as of civilizations capable of interstellar communication in our Galaxy.}, } @article {pmid7107068, year = {1982}, author = {Collins, SJ and Fialkow, PJ}, title = {Clonal nature of spontaneous AKR leukemia: studies utilizing the X-linked enzyme phosphoglycerate kinase.}, journal = {International journal of cancer}, volume = {29}, number = {6}, pages = {673-676}, doi = {10.1002/ijc.2910290612}, pmid = {7107068}, issn = {0020-7136}, support = {GM 15253/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Clone Cells ; Female ; Genetic Linkage ; Heterozygote ; Leukemia, Experimental/*genetics ; Male ; Mice ; Mice, Inbred AKR ; Mosaicism ; Neoplasm Transplantation ; Phenotype ; Phosphoglycerate Kinase/*analysis/genetics ; Thymoma/*genetics ; Thymus Neoplasms/*genetics ; X Chromosome ; }, abstract = {AKR mice heterozygous at the X-linked phosphoglycerate kinase (PGK) locus were used in experiments to determine the number of cells from which spontaneous thymic leukemias (thymomas) develop. Because only one of the two X-chromosomes is active in XX somatic cells, thymic leukemias that are clonal should display either type A or type B PGK, but not both, while those that are multicellular in origin may exhibit both enzymes. Spontaneous thymomas from 19 PGK heterozygous animals expressed exclusively (11 tumors) or predominantly (8 tumors) a single enzyme in contrast to non-malignant tissue from these animals which expressed both enzyme types in approximately equal ratios. When primary tumors expressing a single or predominant enzyme type were transplanted, the transplanted tumors invariably displayed the PGK phenotype that predominated in the initial tumor indicating that the minor PGK component was not contributed by malignant cells. These results indicate that spontaneous AKR leukemias are clonal.}, } @article {pmid7043281, year = {1982}, author = {Wintersberger, U}, title = {Chemical carcinogenesis -- the price for DNA - repair?.}, journal = {Die Naturwissenschaften}, volume = {69}, number = {3}, pages = {107-113}, pmid = {7043281}, issn = {0028-1042}, mesh = {Animals ; Base Sequence ; Carcinogens/*pharmacology ; Cell Differentiation ; *Cell Transformation, Neoplastic ; Cell Transformation, Viral ; *DNA Repair ; DNA Replication/drug effects ; Mice ; Retroviridae/genetics ; Teratoma/physiopathology ; Transcription, Genetic/*drug effects ; }, abstract = {This essay examines the possibility of merging the mutation theory of cancer with the hypothesis that cancer is a change in the state of the differentiation of cells. It is suggested that during normal development DNA rearrangements occur, concerning genes which code for differentiation specific cell communication proteins. These proteins are responsible for the proper functioning of growth control in a multicellular organism. DNA-damaging agents - mutagens - induce DNA repair enzymes, some of which may catalyse illegitimate genome rearrangements, thus leading to a change of the balance between growth and differentiation. A cell with a selective advantage may arise and become the origin of a tumor.}, } @article {pmid7041459, year = {1982}, author = {Galaktionov, VG}, title = {[Immunity in the evolution of multicellular animals].}, journal = {Uspekhi sovremennoi biologii}, volume = {93}, number = {1}, pages = {149-165}, pmid = {7041459}, issn = {0042-1324}, mesh = {Amphibians/immunology ; Animals ; Antigens/immunology ; *Biological Evolution ; Eukaryota/immunology ; Histocompatibility ; Histocompatibility Antigens/immunology ; *Immunity ; Immunity, Innate ; Immunogenetics ; Immunoglobulins/genetics/immunology ; Invertebrates/immunology ; Lymphocytes/immunology ; Mutation ; Phagocytosis ; Vertebrates/immunology ; }, } @article {pmid7326324, year = {1981}, author = {Lammel, E}, title = {A theoretical study on the sucrose gap technique as applied to multicellular muscle preparations. II. Methodical errors in the determination of outward currents.}, journal = {Biophysical journal}, volume = {36}, number = {3}, pages = {555-573}, pmid = {7326324}, issn = {0006-3495}, mesh = {Electrophysiology ; Membrane Potentials ; Models, Biological ; Muscles/*metabolism ; Potassium/*metabolism ; Sodium Chloride/metabolism ; Sucrose/metabolism ; }, abstract = {This paper presents a mathematical model for analyzing systematic errors associated with the membrane conductance of multicellular muscle preparations as determined in a sucrose gap apparatus. The errors arise because of the interdiffusion of sucrose and saline in the interstitial fluid spaces, which results (a) in spatial variations of equilibrium potentials, membrane conductance, and solution conductivity, and (b) in the existence of a liquid junction potential. The model was applied to simulate the measurement of outward currents predominantly carried by potassium ions; time variations were not considered. Output current/voltage (I/V) curves were computed and compared with the membrane I/V relationship used in the computation. The output curves look very much like experimental results but are distorted considerably from the membrane I/V relationship: (a) under favorable conditions (negligible shunt current), the membrane current is overestimated over the entire range of membrane potential, (b) regions with negative slope conductance of I/V relations with "anomalous rectifier" properties are found to be less pronounced or even absent, and (c) resting potentials may be either increased or reduced. The origin of these errors is related to currents emerging from the sucrose compartment (local circuit as well as externally applied currents). Their dependence on several experimental parameters is discussed.}, } @article {pmid7198713, year = {1981}, author = {Berkovich SYa, }, title = {A cybernetical model of the internal cellular clock.}, journal = {Medical hypotheses}, volume = {7}, number = {11}, pages = {1347-1357}, doi = {10.1016/0306-9877(81)90125-0}, pmid = {7198713}, issn = {0306-9877}, mesh = {Animals ; *Biological Clocks ; Cell Division ; Cybernetics ; DNA Replication ; Female ; Humans ; Mathematics ; *Models, Genetic ; Pregnancy ; Twins, Monozygotic ; }, abstract = {A model of a cell-labeling mechanism for the development tree of a multicellular organism is suggested. The cell-labeling information is assumed to originate because the DNA strands are complementary, rather than identical, so a pair of replicated DNA can carry different information content to newly created pairs of chromosomes. This mechanism can serve as an internal cellular clock and as one of the factors involved in the control of cell differentiation. Some possible structures were analyzed by means of the mathematical theory of reliability and compared with the results of Hayflick's experiments on limited cells'lifetime. The external destruction of the clock mechanism can remove limitations on cell's reproductions and is considered as a cause of carcinogenesis; the model exhibits cumulative and threshold effects. The cell-labeling mechanism of the model is able to provide sometimes equivalent labeling for the initial zygote division as a necessary condition for the appearance of monozygote twins; it is most likely that this may occur only for pairs of monozygote twins with the probability equal to an integer power of 1/2.}, } @article {pmid7197587, year = {1981}, author = {Wibe, E and Lindmo, T and Kaalhus, O}, title = {Cell kinetic characteristics in different parts of multicellular spheroids of human origin.}, journal = {Cell and tissue kinetics}, volume = {14}, number = {6}, pages = {639-651}, doi = {10.1111/j.1365-2184.1981.tb00849.x}, pmid = {7197587}, issn = {0008-8730}, mesh = {Cell Line ; DNA, Neoplasm/analysis ; Female ; Humans ; *Interphase ; Kinetics ; *Mitosis ; Probability ; Uterine Cervical Neoplasms/*pathology ; }, abstract = {The growth fraction, the cell cycle time, and the duration of the individual cell cycle phases were determined as a function of distance from the surface of multicellular spheroids of the human cell line NHIK 3025. The techniques employed were percentage of labelled mitoses and labelling index measurements after autoradiography and flow cytometric measurements of DNA histograms. To separate cell populations from the different parts of the spheroid, fractionated trypsinization was employed. The results were compared with corresponding values in NHIK 3025 cell populations grown as monolayer cultures. While practically all cells in exponentially growing monolayer populations are proliferating, the growth fraction was between 0.6 and 0.7 in the outer parts of the spheroid. The inner region was mainly occupied by a necrotic mass. The proliferating fraction of the recognizable cells in the inner region was slightly below 0.5. The mean cell cycle time of NHIK 3025 cells in monolayer culture is 18 hr. The mean cell cycle time of proliferating cells in the periphery of the spheroid was 30 hr, compared to 41 hr in the inner region (150 micrometer from the spheroid surface). All phases of the cell cycle were prolonged compared to populations of exponentially growing monolayer cells. Within each part of the spheroid the distribution of cell cycle times was considerably broadened compared with monolayer populations.}, } @article {pmid7031747, year = {1981}, author = {Gensler, HL and Bernstein, H}, title = {DNA damage as the primary cause of aging.}, journal = {The Quarterly review of biology}, volume = {56}, number = {3}, pages = {279-303}, doi = {10.1086/412317}, pmid = {7031747}, issn = {0033-5770}, support = {GM27219/GM/NIGMS NIH HHS/United States ; }, mesh = {*Aging ; Animals ; Brain/metabolism ; Cell Survival ; DNA/*metabolism/radiation effects ; *DNA Repair ; DNA Replication ; DNA, Single-Stranded/metabolism ; Genes ; Models, Biological ; Muscle Development ; Mutation ; Transcription, Genetic ; Ultraviolet Rays ; }, abstract = {DNA damage appears to be ubiquitous in the biological world, as judged by the variety of organisms which have evolved DNA-repair systems. Previously, it was proposed that germ-line DNA of multicellular organisms may be protected from damage, and consequently from aging, by efficient recombinational repair during meiosis. The somatic line, however, may be vulnerable to the accumulation of DNA damage, and hence undergo aging, owing to relatively less repair. Although the DNA lesions most important in aging are not known yet, there is evidence for serveral types of endogenous damage. DNA lesions have been shown to interfere with transcription and replication, and so lead to loss of cell function and death. In mammals, there is a progressive decline of function in many different tissues with increasing age. Deterioration of central nervous system functions appears to be a critical part of the aging process. This may be due to the low DNA repair capacity which is found in postmitotic brain tissue, and which could result in the accumulation of DNA lesions in this tissue. Also reviewed is evidence that species longevity is directly related to tissue DNA-repair capacity and that aging may be accelerated by treatment with DNA-damaging agents, or in individuals with genetically defective repair. Although it has been frequently postulated that somatic mutation may be cause of aging, current evidence suggests that it is probably less important than DNA damage. A prominent theory on the evolution of aging, which attributes special importance to genes that are advantagous in youth but are deleterious later on, is discussed in terms of regulatory genes that reduce DNA repair as cells differentiate to the postmitotic state. Finally, we hypothesize that the factors which determine maximum longevity of individuals in a population are the rate of occurrence of DNA damage, the rate of DNA repair, the degree of cellular redundancy, and the extent of exposure to stress.}, } @article {pmid6172909, year = {1981}, author = {Mustafin, AM}, title = {[One of the possible mechanisms of growth regulation in multicellular organisms and its application to the problems of aging and carcinogenesis].}, journal = {Uspekhi sovremennoi biologii}, volume = {92}, number = {2}, pages = {261-277}, pmid = {6172909}, issn = {0042-1324}, mesh = {*Aging ; Animals ; Biological Evolution ; Cell Cycle ; Cell Differentiation ; Cell Survival ; Cell Transformation, Neoplastic/pathology ; DNA/physiology ; DNA, Neoplasm/physiology ; *Growth ; Growth Substances/physiology ; Humans ; Neoplasms/*etiology/genetics ; Neoplasms, Experimental/*etiology/genetics ; RNA/physiology ; RNA, Neoplasm/physiology ; Regeneration ; }, } @article {pmid6980450, year = {1981}, author = {Lindahl-Kiessling, K and Karlberg, I}, title = {Unicellular or multicellular origin of human T-lymphocyte colonies in soft agar?.}, journal = {Scandinavian journal of immunology}, volume = {15}, number = {5}, pages = {525-530}, doi = {10.1111/j.1365-3083.1982.tb00680.x}, pmid = {6980450}, issn = {0300-9475}, mesh = {Agar ; Bromodeoxyuridine/metabolism ; Cell Aggregation ; Cell Division ; Cell Movement ; Clone Cells/cytology ; Humans ; Lymphocyte Activation ; T-Lymphocytes/*cytology/physiology ; Tetradecanoylphorbol Acetate/pharmacology ; }, abstract = {Human peripheral lymphocytes were cultivated in soft agar or agarose, containing 3H-thymidine or bromodeoxyuridine (BrdU), which is an analogue of thymidine readily incorporated into deoxyribonucleic acid by lymphocytes. Colonies were isolated and analysed by autoradiography or stained with the fluorescence-plus-Giemsa technique, which identifies cells that have passed one, two, three, or more replication cycles with incorporation of BrdU. Colonies contained cells in their first and second division cycle together with later generations. The labelling index was very high. Consequently, it was concluded that, at least without special precautions being taken, lymphocyte colonies in semi-liquid medium are likely to grow through recruitment of mobile cells as well as through divisions within the colonies. Thus, T-cell growth in gels seems to be a matter of recognition between activated blast cells rather than monoclonal growth.}, } @article {pmid6970773, year = {1981}, author = {Singer, JW and Ernst, C and Whalen, CK and Steinmann, L and Fialkow, PJ}, title = {Single or multicellular origin of human T lymphocyte colonies in vitro: modification by 12-o-tetradecanoylphorbol 13-acetate (TPA).}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {126}, number = {4}, pages = {1390-1392}, pmid = {6970773}, issn = {0022-1767}, support = {16448//PHS HHS/United States ; 20180//PHS HHS/United States ; CA 18029/CA/NCI NIH HHS/United States ; }, mesh = {Cells, Cultured ; Dose-Response Relationship, Drug ; Female ; Glucosephosphate Dehydrogenase/metabolism ; Heterozygote ; Humans ; Peroxidases/metabolism ; Phorbols/*pharmacology ; Rosette Formation ; *T-Lymphocytes/enzymology ; Tetradecanoylphorbol Acetate/*pharmacology ; }, abstract = {The assumption that human T lymphocyte colonies have a unicellular origin has been directly tested with peripheral blood mononuclear cells from 2 women heterozygous for the common X-linked glucose-6-phosphate dehydrogenase (G-6-PD) gene (GdB) and the variant GdA. T cells were cultured in semisolid medium in the presence of phytohemagglutinin (PHA) and T lymphocyte growth factor with or without preincubation in suspension culture with PHA (2-stage and 1-stage assays, respectively). The enzyme type of individual T cell colonies was then determined electrophoretically at the lowest colony density with adequate growth (usually less than 100 colonies/dish). In the 2-stage system, 90 of 97 tested colonies had equal amounts of A and B enzyme activities suggesting multicellular origin of the colonies. Similarly, in the single-stage system, 21 of 31 colonies had both A and B enzymes. Increasing the density of the soft agar did not influence the frequency of A/B colonies. However, when 12-O-tetradecanoylphorbol 13-acetate (TPA), a promoter of T cell colony growth shown in other systems to inhibit metabolic cooperation, was added, a striking decrease in frequency of colonies with both G-6-PD types was found. In the 2-stage culture, 0 of 9 colonies had a double-enzyme type and in the single-stage system, the frequency of A/B colonies declined to 9 of 34 (p less than 0.025). The data suggest that despite the apparent multicellular origin of T cell colonies in cultures with TPA, most colonies do originate from single cells when cultured with TPA at low colony densities. Stimulation of cell growth or inhibition of metabolic cooperation between cells by TPA are possible explanations for these differences.}, } @article {pmid7275355, year = {1981}, author = {Reddy, AL and Fialkow, PJ}, title = {Effect of solvents on methylcholanthrene-induced carcinogenesis in mice.}, journal = {International journal of cancer}, volume = {27}, number = {4}, pages = {501-504}, doi = {10.1002/ijc.2910270413}, pmid = {7275355}, issn = {0020-7136}, support = {GM 15253/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Benzene/pharmacology ; Female ; Fibrosarcoma/chemically induced/enzymology/pathology ; Methylcholanthrene ; Mice ; Mice, Inbred BALB C ; Oils/pharmacology ; Phenotype ; Phosphoglycerate Kinase/genetics ; Plants ; Sarcoma, Experimental/chemically induced/enzymology/*pathology ; Solvents/*pharmacology ; }, abstract = {We have shown previously, with X-chromosome linked phosphoglycerate kinase (PGK) cell markers, that the fibrosarcomas induced in mice by subcutaneous injection of 0.2-2.0 mg of methylcholanthrene (MCA) dissolved in olive oil had a multicellular origin. In this study we used a constant dose of MCA injected subcutaneously and compared the effects on tumorigenesis of using benzene or olive oil as the solvents. The benzene and olive oil groups differed in tumor incidence (100% versus 50%), location (muscle versus skin), and type (rhabdomyosarcomas versus fibrosarcomas). Each of the nine olive-oil MCA-induced tumors showed both PGK enzyme types, whereas 13 ot 16 tumors induced by MCA in benzene displayed only a single PGK type. This difference in PGK phenotypes suggests that the MCA-benzene neoplasms arose from one or a few cells. We conclude from these results that the nature of the solvent plays an important role in the type and number of cells from which tumors induced by subcutaneous injection of MCA arise.}, } @article {pmid7250481, year = {1981}, author = {Lees, RK and Sordat, B and MacDonald, HR}, title = {Multicellular tumor spheroids of human colon carcinoma origin. Kinetic analysis of infiltration and in situ destruction in a xenogeneic (murine) host.}, journal = {Experimental cell biology}, volume = {49}, number = {4}, pages = {207-219}, pmid = {7250481}, issn = {0304-3568}, mesh = {Animals ; Cell Division ; Cell Line ; Cell Membrane/ultrastructure ; Cell Survival ; Colonic Neoplasms/*pathology ; *Graft Rejection ; Humans ; Leukocytes ; Macrophages ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; *Transplantation, Heterologous ; }, abstract = {The relationship between destruction and concomitant host cell infiltration of human tumor xenografts has been quantitatively investigated by using the multicellular tumor spheroid model. Multicellular tumor spheroids of HT-29 human colon carcinoma cells were grown in vitro and subsequently implanted in the peritoneal cavity of BALB/c mice. At various times thereafter, spheroids were recovered and dissociated and their viability was quantitatively assessed by using a clonogenic assay. Little damage to spheroids was observed during the initial 4 days after implantation, but essentially complete destruction (greater than 99% reduction in clonogenic tumor cells) occurred between days 4 and 7. In parallel studies, host cell infiltration was assessed by light and electron microscopy both in situ on sections and on dissociated suspensions of spheroid cells. The data demonstrate the value of utilizing a model system in which both functional and morphological techniques can be combined in a quantitative assessment of the relationship between host cell infiltration and graft destruction in situ.}, } @article {pmid6273596, year = {1981}, author = {Akiyama, SK and Yamada, KM and Hayashi, M}, title = {The structure of fibronectin and its role in cellular adhesion.}, journal = {Journal of supramolecular structure and cellular biochemistry}, volume = {16}, number = {4}, pages = {345-348}, doi = {10.1002/jsscb.1981.380160405}, pmid = {6273596}, issn = {0275-3723}, mesh = {Amniotic Fluid/analysis ; Animals ; *Cell Adhesion ; Cell Membrane/metabolism ; Chickens ; Female ; Fibronectins/*physiology ; Humans ; Molecular Weight ; Pregnancy ; Protein Binding ; Receptors, Cell Surface/physiology ; Receptors, Fibronectin ; }, abstract = {Fibronectin is a large, adhesive glycoprotein which is found in a number of locations, most notably on cell surfaces, in extracellular matrixes, and in blood. Fibronectin had been detected in all vertebrates tested and in many invertebrates. Its presence in sponges is significant because this suggests that fibronectin may have appeared very early in evolution, possibly with the most primitive multicellular organisms. Cellular and plasma fibronectins have many striking similarities. However, the locations of the polypeptide chain differences between these two proteins indicate that plasma fibronectin cannot be derived from cellular fibronectin by means of simple post-translational proteolysis. Instead, these different types of fibronectin may be products of different genes or of differentially spliced messenger RNA molecules. Amniotic fluid fibronectin is possibly a third form of the protein. Cellular and plasma fibronectins are composed of at least six protease-resistant domains which contain specific binding sites for actin, gelatin, heparin, Staphylococcus aureus, transglutaminase, fibrin, DNA, and a cell surface receptor. The relative locations of these domains have been mapped in the primary structure of fibronectin. The cell surface receptor for fibronectin has not been positively identified, but may be a glycoprotein, a glycolipid, or a complex of the two. Although cell-substratum adhesion is mediated by fibronectin, the locations of the areas of closest approach of the cell to the substratum (the adhesion plaques) and fibronectin are not coincident under conditions of active cell growth. Under conditions of cell growth arrest in low serum concentrations, some fibronectin may become localized at the adhesion plaques. Models describing the domain structure of fibronectin and the molecular organization of the adhesion plaque area are presented.}, } @article {pmid7471046, year = {1980}, author = {Freyer, JP and Sutherland, RM}, title = {Selective dissociation and characterization of cells from different regions of multicell tumor spheroids.}, journal = {Cancer research}, volume = {40}, number = {11}, pages = {3956-3965}, pmid = {7471046}, issn = {0008-5472}, support = {CA-11051/CA/NCI NIH HHS/United States ; CA-11198/CA/NCI NIH HHS/United States ; CA-20329/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Aggregation ; Cell Cycle ; Cell Division ; Cell Survival ; Cells, Cultured ; Clone Cells/pathology ; Female ; Mammary Neoplasms, Experimental/pathology ; Mice ; Neoplasms, Experimental/*pathology ; }, abstract = {A technique has been developed which takes advantage of the spherical symmetry of EMT6/Ro multicellular tumor spheroids to isolate subpopulations of cells originating from various locations in the spheroid structure. The method involves gently exposing spheroids to a dilute trypsin solution at 18 to 20 degrees in specially designed dishes on a rotary shaker. Under these conditions, cells are released only from the outer spheroid surface; successive trypsin treatments dissociate cells from increasing depths in the spheroid. Measurements of the spheroid diameter and rate of cell dissociation demonstrated the reproducibility of the technique. Observations of histological sections showed that trypsin was active only over a small distance into the spheroid. Characterization of the cells isolated indicated that cell volume, membrane integrity, and clonogenic capacity all decreased for cells located in inner spheroid regions. Autoradiography and DNA content analysis by flow cytometry established that outer region cells were actively proliferating while inner region cells were in a nonproliferative state. There was a significant number of cells arrested with S- and G2-phase DNA contents as well as a large number arrested with a G1 DNA content, similar to recent findings for nonproliferating cells in tumors.}, } @article {pmid7459394, year = {1980}, author = {Trincher, K}, title = {[The information content of intracellular water and its accumulation in embryo- and phylogenesis (author's transl)].}, journal = {Biological cybernetics}, volume = {39}, number = {1}, pages = {1-10}, pmid = {7459394}, issn = {0340-1200}, mesh = {Animals ; Body Fluids/*physiology ; Cybernetics ; *Embryology ; Intracellular Fluid/*physiology ; Mathematics ; *Models, Biological ; *Phylogeny ; Thermodynamics ; }, abstract = {The nucleo-free erythrocytes is presented as the simplest differentiated cell whose energy-exchange has the single purpose of preserving the cell structure; this structure is based on the regular quasi-crystalline state of intracellular water, which is expressed by the negative entropy (-SW) and the temperature TW which is higher than the temperature of the extracellular water T. The information content of intracellular water, JW is proportional to the temperature difference: JW approximately delta T = TW - T. The regular state of intracellular water is maintained by the basal metabolism that takes place in the membrane of the differentiated cell. The energy exchange, i.e., the absorption of free energy and the liberation of an equivalent amount of heat, occurs in the form of work cycles of the enzyme-water-complexes in the cell membrane. The differentiated cell of the multicellular animal organism is the result of embryogenetic processes accompanied by heat-liberation. The specific heat-liberation, i.e., the heat produced by a single cell, begins with a quasi-zero value of the fertilized egg cell and grows with acceleration to a maximum value at the end of embryogenesis. This process of acceleration of heat-liberation is caused by the entrance of the water from the outer medium into the embryonic cell; the water undergoes the phase-change "fluid yields crystal" with heat-liberation. The intracellular water within the embryonic cell becomes structurated; this is also accompanied by growing heat-liberation. The thermodynamic characteristic of embryo genetic development is expressed by the principle of the maximum of velocity of entropy production of the cell at the end state of the process of differentiation. This principle applied to phylogenetics, leads to the formulation of the principle of accumulation of biological information: J(t). In the course of evolution living systems are able not only to store information of past generations, but also to create information: J(t) approximately e-1nt1!, where t is the time of phylogenesis.}, } @article {pmid7382889, year = {1980}, author = {Conyers, RA and Fazzalari, NL}, title = {Some thoughts on evolution.}, journal = {Medical hypotheses}, volume = {6}, number = {1}, pages = {77-84}, doi = {10.1016/0306-9877(80)90034-1}, pmid = {7382889}, issn = {0306-9877}, mesh = {Animals ; *Biological Evolution ; Cell Differentiation ; Environment ; Genetic Code ; *Mutation ; }, abstract = {The sparsity of transitional forms and the abrupt appearance of higher taxa in the fossil record are enigmas for the neo-Darwinian theory of evolution. If the cell is considered to be a steady state system then mutations affecting non-regulatory proteins will have far less effect on the steady state than mutations affecting regulatory proteins. This latter type of mutation, when expressed in multicellular biological systems, is a sufficient explanation for the discontinuities observed between species. Such a mechanism, however, has its own implications for any theory of evolution.}, } @article {pmid6155156, year = {1980}, author = {Cavalier-Smith, T}, title = {r- and K-tactics in the evolution of protist developmental systems: cell and genome size, phenotype diversifying selection, and cell cycle patterns.}, journal = {Bio Systems}, volume = {12}, number = {1-2}, pages = {43-59}, doi = {10.1016/0303-2647(80)90037-4}, pmid = {6155156}, issn = {0303-2647}, mesh = {Animals ; *Biological Evolution ; *Cell Cycle ; Eukaryota/*physiology ; Fungi/*physiology ; *Genes ; Heterochromatin/metabolism ; Phenotype ; Polyploidy ; RNA/metabolism ; Selection, Genetic ; }, abstract = {I outline the significance for protist evolution of the r-, K-selection spectrum,, and of my earlier theory that the most fundamental way organisms adapt to this spectrum is by evolutionary variations in their cell volumes, cell growth rates and genome sizes. Then I introduce the concept of phenotype diversifying selection; this refers to those selective forces which favour an increase in the number of phenotypes produced during a single life cycle by an organism's genotype and epigenetic system. These ideas are then used to discuss the evolution of protist development, with special reference to modifications of the cell cycle whose evolutionary causes and consequences can be related to K-selection for large size and r-selection for rapid reproduction. The significance of multiple fission, syncytia, multicellularity, nuclear dimorphism plus polyploidy, and reversible polyploidy, is treated in detail. Predictions are made of the effects of these different developmental patterns on genome size and the distribution and amounts of nucleoskeletal RNA and heterochromatin. I suggest that heterochromatin exists primarily because of phenotype diversifying selection for differing nuclear volumes. The possibility of applying these ideas to other cell properties like mitotic or cytokinetic mechanisms is also briefly discussed.}, } @article {pmid508944, year = {1979}, author = {Singer, JW and Fialkow, PJ and Dow, LW and Ernst, C and Steinmann, L}, title = {Unicellular or multicellular origin of human granulocyte-macrophage colonies in vitro.}, journal = {Blood}, volume = {54}, number = {6}, pages = {1395-1399}, pmid = {508944}, issn = {0006-4971}, mesh = {Blood Protein Electrophoresis ; Cell Communication ; Cell Differentiation ; Cells, Cultured ; Dose-Response Relationship, Drug ; Glucose-6-Phosphate Isomerase/blood ; Glucosephosphate Dehydrogenase/blood ; Granulocytes/*cytology ; Humans ; Macrophages/*cytology ; Male ; }, abstract = {The assumption that human granulocyte-macrophage colonies have a unicellular origin and thus are true clones has been directly tested. Cells from seven females heterozygous for the common glucose-6-phosphate dehydrogenase (G-6-PD) gene (GdB) and the variant GdA were cultured in semisolid medium for granulocyte-macrophage colony growth and the enzyme type of individual colonies was determined. When the colony density was less than 20/dish, more than 95% of colonies had either type A or type B G-6-PD, but not both. At colony densities greater than 30/dish, between 15% and 75% of colonies had both enzyme types and therefore arose from more than one cell. These results are consistent with a unicellular origin for the colonies only when they are cultured at low densities. With increasing colony density, there was a greater frequency of colonies with both type A and type B activity, suggesting that accurate enumeration of committed stem cells can only be performed at low colony concentrations.}, } @article {pmid512585, year = {1979}, author = {Reddy, AL and Fialkow, PJ}, title = {Multicellular origin of fibrosarcomas in mice induced by the chemical carcinogen 3-methylcholanthrene.}, journal = {The Journal of experimental medicine}, volume = {150}, number = {4}, pages = {878-887}, pmid = {512585}, issn = {0022-1007}, mesh = {Animals ; Clone Cells/enzymology ; Culture Techniques ; Fibrosarcoma/*chemically induced/enzymology/pathology ; Isoenzymes/analysis ; Male ; *Methylcholanthrene ; Mice ; Neoplasms, Experimental/chemically induced/enzymology/pathology ; Organ Specificity ; Phenotype ; Phosphoglycerate Kinase/analysis ; }, abstract = {The cellular origin of tumors induced by the chemical carcinogen 3-methylcholanthrene (MCA) was studied in mice with X-chromosome inactivation mosaicism. Because only one of the two X-chromosomes is active in XX somatic cells, a female heterozygous at the X-linked phosphoglycerate kinase (PGK-1) locus for the usual Pgk-1b gene and the variant Pgk-1a has two populations of cells, in the cells of one population, Pgk-1b is active and B-type enzyme is synthesized, whereas in cells of the other population, A-type enzyme is produced. Both enzyme types are found in normal tissues from these mosaic mice. A tumor developing from a single cell exhibits only one of the two PGK enzyme types, whereas a tumor with a multicellular origin expresses both enzymes (i.e., it has a double-enzyme phenotype). Five fibrosarcomas developing at the site of injection of 0.2 or 2.0 mg of MCA were analyzed. 36 of 38 fragments from the five tumors had double-enzyme PGK phenotypes. One piece from each of two tumors showed a single-enzyme phenotype. Histological, cell culture, and cloning studies indicate that the double-enzyme phenotypes reflect the presence of both types of malignant cells and not admixture of normal with neoplastic elements in the specimens tested for PGK. The results suggest strongly that these fibrosarcomas have a multicellular origin.}, } @article {pmid229158, year = {1979}, author = {Heitz, PU and Kasper, M and Polak, JM and Klöppel, G}, title = {Pathology of the endocrine pancreas.}, journal = {The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society}, volume = {27}, number = {10}, pages = {1401-1402}, doi = {10.1177/27.10.229158}, pmid = {229158}, issn = {0022-1554}, mesh = {Adenoma, Islet Cell/*pathology ; Histocytochemistry ; Humans ; Islets of Langerhans/*pathology ; Pancreatic Neoplasms/*pathology ; Pancreatic Polypeptide/analysis ; Radioimmunoassay ; Somatostatin/analysis ; }, abstract = {An immunocytochemical analysis of 94 pancreatic endocrine tumors revealed that 73 tumors were multicellular. Significant amounts of somatostatin and human pancreatic polypeptide were found by radioimmunoassay in extracts of 19 and 17 tumors resp., in addition to the hormone causing the clinical syndrome. Numerous tumors contained ductular structures. In the surrounding pancreatic parenchyma a proliferation of small ducts and budding-off from the ductular epithelium of endocrine cells was often observed. These features are hallmarks of nesidioblastosis of the endocrine pancreas which is a hyperplasia. In multiple endocrine neoplasia I hyperplasia of the endocrine pancreas is combined with larger nodules, currently labeled tumors. On the basis of these findings it is conceivable that pancreatic endocrine tumors are not primarily neoplastic and autonomous but that they are rather of hyperplastic origin.}, } @article {pmid503456, year = {1979}, author = {Schidlowski, M}, title = {Antiquity and evolutionary status of bacterial sulfate reduction: sulfur isotope evidence.}, journal = {Origins of life}, volume = {9}, number = {4}, pages = {299-311}, pmid = {503456}, issn = {0302-1688}, mesh = {Bacteria/*metabolism ; Biological Evolution ; Origin of Life ; Oxidation-Reduction ; Sulfates/*metabolism ; Sulfur Isotopes ; }, abstract = {The presently available sedimentary sulfur isotope record for the Precambrian seems to allow the following conclusions: (1) In the Early Archaean, sedimentary delta 34S patterns attributable to bacteriogenic sulfate reduction are generally absent. In particular, the delta 34S spread observed in the Isua banded iron formation (3.7 x 10(9) yr) is extremely narrow and coincides completely with the respective spreads yielded by contemporaneous rocks of assumed mantle derivation. Incipient minor differentiation of the isotope pattersn notably of Archaean sulfates may be accounted for by photosynthetic sulfur bacteria rather than by sulfate reducers. (2) Isotopic evidence of dissimilatory sulfate reduction is first observed in the upper Archaean of the Aldan Shield, Siberia (approximately 3.0 x 10(9) yr) and in the Michipicoten and Woman River banded iron formations of Canada (2.75 x 10(9) yr). This narrows down the possible time of appearance of sulfate respirers to the interval 2.8--3.1 x 10(9) yr. (3) Various lines of evidence indicate that photosynthesis is older than sulfate respiration, the SO4(2-) Utilized by the first sulfate reducers deriving most probably from oxidation of reduced sulfur compounds by photosynthetic sulfur bacteria. Sulfate respiration must, in turn, have antedated oxygen respiration as O2-respiring multicellular eucaryotes appear late in the Precambrian. (4) With the bulk of sulfate in the Archaean oceans probably produced by photosynthetic sulfur bacteria, the accumulation of SO4(2-) in the ancient seas must have preceded the buildup of appreciable steady state levels of free oxygen. Hence, the occurrence of sulfate evaporites in Archaean sediments does not necessarily provide testimony of oxidation weathering on the ancient continents and, consequently, of the existence of an atmospheric oxygen reservoir.}, } @article {pmid230410, year = {1979}, author = {Litvay, M}, title = {A possible role of estrogens in carcinogenesis of non-target tissues.}, journal = {Medical hypotheses}, volume = {5}, number = {9}, pages = {953-968}, doi = {10.1016/0306-9877(79)90044-6}, pmid = {230410}, issn = {0306-9877}, mesh = {Animals ; Biological Evolution ; Cell Nucleus/physiology ; Estrogens/*physiology ; Humans ; Mitosis ; Neoplasms/*etiology ; Receptors, Cell Surface/*physiology ; }, abstract = {The mitogenic action of the estrogen-receptor complex is supposedly similar in both normal and malignant target tissues. As receptors are present in several types of non-target tissues, in the case of lesions at the nuclear acceptor sites, the complex in those might be able to cause successive mitoses. Estrogen-dependent tumors of non-target tissues have been reported by several investigators. In normal and malignant cells of the breast and some other types of non-endocrine cells, the ability to produce their own estrogens (from circulating precursors) has been shown. The locally formed estrogens might have a role in the initiation of some malignant transformations. Indications of this process are the switching to estrogen production of some neoplastic endocrine or undifferentiated cells, certain ectopic effects displayed by some cancerous tissues, and the possible roles of GH, PRL and cholesterol in the development of some malignancies. The present endocrine system for the synthesis of the sexual hormones might be a specialization of a system at the cellular level. Polypeptide hormones might evolve from regulatory parts of cyclases or phosphodiesterases. Traces of the original biological processes might still be maintained by several cell-types.}, } @article {pmid459991, year = {1979}, author = {Seely, S}, title = {Basic principles of cellular organization.}, journal = {Medical hypotheses}, volume = {5}, number = {4}, pages = {437-446}, doi = {10.1016/0306-9877(79)90109-9}, pmid = {459991}, issn = {0306-9877}, mesh = {Animals ; *Cell Differentiation ; Ectoderm/physiology ; Endoderm/physiology ; Female ; Germ Layers/*physiology ; Humans ; Mesoderm/physiology ; Phylogeny ; }, abstract = {The hypothesis is put forward that the division of the animal body into three germ layers represents not only histological, but also functional specialization, the ectoderm taking over functions through which the animal is in contact with, acted upon or reacts to the external world, the entoderm metabolism and the mesoderm architectural and mechanical organization. This is assumed to mean that the tasks of life have been divided into three large function domains at an early stage of multicellular evolution, each germ layer taking over one domain and developing largely independently of the other two in the further course of phylogeny. The germ layers are autonomous in their own spheres, giving the body, in effect, a tripartite government. The potentiality of conceptual thought is inherent in all germ layers, reaching a high state of development in the entoderm and mesoderm at a much earlier stage of development than in the ectoderm. The animal body, as a whole, is in control of all its biologic activities; it is a self-designing, self-developing and self-perpetuating entity. The control of cellular organization is a mesodermal task.}, } @article {pmid109976, year = {1979}, author = {Kozlov, AV and Ivanova, SB and Lipskaia, AA and Bers, EP and Vodop'ianova, LG}, title = {[Immunofluorescent study of the basic chromosomal protein set of green algae and Euglena].}, journal = {Tsitologiia}, volume = {21}, number = {4}, pages = {459-465}, pmid = {109976}, issn = {0041-3771}, mesh = {Animals ; Cattle ; Chlamydomonas/genetics/immunology ; Chlorophyta/*genetics/immunology ; Chromosomes/*analysis ; Euglena gracilis/*genetics/immunology ; Fluorescent Antibody Technique ; Histones/immunology ; Plant Proteins/*analysis ; Thymus Gland/immunology ; }, abstract = {Using antisera to fractions H1, H2a, H3 and H4 of the calf thymus histones, a comparative immunofluorescent investigation of these proteins in the nuclei of Chlamydomonas reinhardii, Haematococcus pluvialis, Dunaliella salina and Euglena gracilis was carried out. It has been shown that according to the immunofluorescent test, the nuclei of these algae contain proteins close to fractions H2a, H3 and H4 of the calf thymus histones. H1 fraction in these algae is either absent or can be considered as a protein immunochemically non-related to H1 fraction of the calf thymus histone. For quantitative evaluation (in units of the immunological distance) of the difference between histones of the algae and of the calf thymus in situ by indirect immunofluorescence, it was suggested to use the ultimate dilutions of antisera to histones. It was shown that the ultimate dilutions were correlated with titres of antisera in the reaction of microcomplement fixation. Such an approach and the data obtained are of interest for studying into the evolution of nucleosome histones in unicellular and multicellular eukaryotes.}, } @article {pmid372199, year = {1978}, author = {Cavalier-Smith, T}, title = {Nuclear volume control by nucleoskeletal DNA, selection for cell volume and cell growth rate, and the solution of the DNA C-value paradox.}, journal = {Journal of cell science}, volume = {34}, number = {}, pages = {247-278}, doi = {10.1242/jcs.34.1.247}, pmid = {372199}, issn = {0021-9533}, mesh = {Animals ; Cell Count ; Cell Cycle ; Cell Nucleus/*metabolism ; Chromosomes ; DNA/*metabolism ; DNA Replication ; Diploidy ; Genes ; Genetic Code ; Heterochromatin ; Humans ; Plants/ultrastructure ; Protein Biosynthesis ; Selection, Genetic ; }, abstract = {The 40,000-fold variation in eukaryote haploid DNA content is unrelated to organismic complexity or to the numbers of protein-coding genes. In eukaryote microorganisms, as well as in animals and plants, DNA content is strongly correlated with cell volume and nuclear volume, and with cell cycle length and minimum generation time. These correlations are simply explained by postulating that DNA has 2 major functions unrelated to its protein-coding capacity: (1) the control of cell volume by the number of replicon origins, and (2) the determination of nuclear volume by the overall bulk of the DNA: cell growth rates are determined by the cell volume and by the area of the nuclear envelope available for nucleocytoplasmic transport of RNA, which in turn depends on the nuclear volume and therefore on the DNA content. During evolution nuclear volume, and therefore DNA content, has to be adjusted to the cell volume to allow reasonable growth rates. The great diversity of cell volumes and growth rates, and therefore of DNA contents, among eukaryotes results from a varying balance in different species between r-selection, which favours small cells and rapid growth rates and therefore low DNA C-values, and K-selection which favours large cells and slow growth rates and therefore high DNA C-values. In multicellular organisms cell size needs to vary in different tissues: size differences between somatic cells result from polyteny, endopolyploidy, or the synthesis of nucleoskeletal RNA. Conflict between the need for large ova and small somatic cells explains why lampbrush chromosomes, nurse cells, chromatin diminution and chromosome elimination evolved. Similar evolutionary considerations clarify the nature of polygenes, the significance of the distribution of haploidy, diploidy and dikaryosis in life cycles and of double fertilization in angiosperms, and of heteroploidy despite DNA constancy in cultured cells, and other puzzles in eukaryote chromosome biology. Eukaryote DNA can be divided into genic DNA (G-DNA), which codes for proteins (or serves as recognition sites for proteins involved in transcription, replication and recombination), and nucleoskeletal DNA (S-DNA) which exists only because of its nucleoskeletal role in determining the nuclear volume (which it shares with G-DNA, and performs not only directly, but also indirectly by coding for nucleoskeletal RNA). Mechanistic and evolutionary implications of this are discussed.}, } @article {pmid705321, year = {1978}, author = {Valentine, JW}, title = {The evolution of multicellular plants and animals.}, journal = {Scientific American}, volume = {239}, number = {3}, pages = {140-6, 148-9, 152-3 passim}, doi = {10.1038/scientificamerican0978-140}, pmid = {705321}, issn = {0036-8733}, mesh = {Animals ; *Biological Evolution ; Fossils ; Phylogeny ; Plant Cells ; }, } @article {pmid692174, year = {1978}, author = {Reiner, JM}, title = {Tissue mosaics and clonal mechanisms of atherogenesis.}, journal = {Mechanisms of ageing and development}, volume = {8}, number = {1}, pages = {15-20}, doi = {10.1016/0047-6374(78)90003-9}, pmid = {692174}, issn = {0047-6374}, mesh = {Arteriosclerosis/enzymology/*genetics/pathology ; Cell Count ; Cell Division ; *Clone Cells ; Female ; Genetic Variation ; Glucosephosphate Dehydrogenase/analysis/genetics ; Heterozygote ; Humans ; *Mosaicism ; Probability ; }, abstract = {It is known that atherosclerotic lesions arising in aortae of females heterozygous for the A and B variants of glucose-6-phosphate dehydrogenase are frequently though not invariably of one enzyme type. The occurrence of heterotypic lesions rules out single-cell origin. However, it is possible to analyze the results of such studies in terms of multicellular atherogenic foci. The variance in enzyme proportions in the normal tissue mosaic permits an assessment of clump or patch size. Then an application of geometrical probability permits the derivation of a relation between the proportion of monotypic lesions and the size and cell number of the original atherogenic focus. Comparison with suitable experimental data gives reasonable estimates of these cell numbers. The influence of selection in the cell population on such estimates is considered.}, } @article {pmid100192, year = {1978}, author = {McDonald, JF and Ayala, FJ}, title = {Gene regulation in adaptive evolution.}, journal = {Canadian journal of genetics and cytology. Journal canadien de genetique et de cytologie}, volume = {20}, number = {2}, pages = {159-175}, doi = {10.1139/g78-018}, pmid = {100192}, issn = {0008-4093}, mesh = {Alcohol Oxidoreductases/genetics ; Animals ; *Biological Evolution ; Drosophila melanogaster ; Genes ; *Genes, Regulator ; *Genetic Variation ; }, abstract = {It has been suggested that gene regulation may play a critical role in adaptive evolution. However, gene regulation has proved to be most refractory to experimental investigation in multicellular organisms. Using specially constructed stocks of Drosophila melanogaster, we have demonstrated the following. (1) The existence in natural populations of ample variation in regulatory genes that modify the activity of alcohol dehydrogenase (ADH), an enzyme coded by a structural gene locus, Adh, located on the second chromosome; the regulatory genes are located on the third chromosome, and thus are not adjacent to the structural locus. (2) The regulatory genes act not by means of post-transcriptional or post-translational modification of the gene product, but rather by controlling the number of ADH molecules; this is consistent with the hypothesis of gene regulation by means of macromolecules specifically binding at control sites adjacent to the structural gene locus. (3) The variation in regulatory genes is adaptively significant; adaptation to higher levels of environmental alcohol takes place not by changes in the Adh structural locus, but by changes in regulatory genes that control the number of ADH molecules in the organisms. Our results provide direct evidence of the importance of gene regulation in eucaryotic evolution.}, } @article {pmid565790, year = {1978}, author = {Rossomando, EF and Maldonado, B and Crean, EV and Kollar, EJ}, title = {Protease secretion during onset of development in Dictyostelium discoideum.}, journal = {Journal of cell science}, volume = {30}, number = {}, pages = {305-318}, doi = {10.1242/jcs.30.1.305}, pmid = {565790}, issn = {0021-9533}, mesh = {Cell Membrane/drug effects ; Dictyostelium/cytology/*enzymology/growth & development ; Kinetics ; Myxomycetes/*enzymology ; Peptide Hydrolases/*metabolism/pharmacology ; }, abstract = {At the onset of development, the single cells of the eukaryotic micro-organism Dictyostelium discoideum secrete proteolytic activity which can be assayed using the insoluble substrate remazolbrilliant blue hide. The activity is not secreted by exponentially growing cells, but does appear extracellularly at the onset of the stationary growth phase. When growth phase cells are resuspended in non-nutrient buffer, proteolytic activity begins to appear outside the cells. It accumulates in the buffer at a rate similar to that observed for 2 glycosidases of lysosomal origin and reaches a maximum after about 2 h of incubation. After 3--4 h incubation, centrifugation of the non-nutrient buffer removes the cells, producing a supernatant which we refer to as conditioned medium. Subsequent experiments with conditioned medium showed: (a) its incubation with purified plasma membranes results in the release of polypeptides which can be recovered and, when displayed on polyacrylamide gels, can be shown to be stage specific; and (b) that conditioned medium can decrease the rate of detachment of cells from a collagen substratum. Both effects can be prevented by the addition of remazolbrilliant blue hide suggesting that they are due to proteolytic activity present in the conditioned medium. Finally, we were able to show that conditioned medium contains components which, when spread over the bottom of plastic Petri dishes, enhance the rate of multicellular structure formation. Additional studies showed that this effect of conditioned medium could also be brought about by components which remained behind on uncoated plastic dishes after the removal of a D. discoideum cell layer. These data may be accommodated to a model in which the protease secreted during the onset of development acts on the cell membrane releasing components which coat the substratum and facilitate migration and multicellular structure formation.}, } @article {pmid412100, year = {1978}, author = {Gown, AM}, title = {Multicellular origin of parathyroid "adenomas".}, journal = {The New England journal of medicine}, volume = {298}, number = {1}, pages = {53-54}, doi = {10.1056/NEJM197801052980116}, pmid = {412100}, issn = {0028-4793}, mesh = {Adenoma/enzymology/*pathology ; Alkaline Phosphatase/analysis ; Animals ; Glucosephosphate Dehydrogenase/analysis ; Haplorhini ; Humans ; Hyperplasia ; Parathyroid Glands/enzymology/pathology ; Parathyroid Neoplasms/enzymology/*pathology ; }, } @article {pmid582507, year = {1978}, author = {Bünning, E}, title = {[Evolution of the circadian organization (author's transl)].}, journal = {Arzneimittel-Forschung}, volume = {28}, number = {10a}, pages = {1811-1813}, pmid = {582507}, issn = {0004-4172}, mesh = {Biological Clocks ; *Biological Evolution ; *Circadian Rhythm ; Humans ; }, abstract = {The evolution of cicadian rhythmicity was possible by selection and mutation. Rhythms which strongly deviate from the circadian rhythms are still existent in case no selective pressure has occurred. An evoluution regressive to those strongly deviating rhythmus can be observed in case the selective pressure has disappeared. The circadian rhythmicity in the various cells and organs of multicellular organisms has not got lost during the evolution. But certain organs have grown important for maintaining the circadian organization within the body and for allowing the synchronization with the light-dark cycles. In addition, contrary to lower organisms, certain processes, e. e. photoreception, are coupled to the circadian rhythm only in specially differentiated organs. The high precision in the clock's running within higher organisms becomes possible by mutual synchronization within the multioscillator system.}, } @article {pmid107686, year = {1978}, author = {Walker, I}, title = {The evolution of sexual reproduction as a repair mechanism. Part I. A model for self-repair and its biological implications.}, journal = {Acta biotheoretica}, volume = {27}, number = {3-4}, pages = {133-158}, pmid = {107686}, issn = {0001-5342}, mesh = {Animals ; *Biological Evolution ; Chromosomes/physiology ; *DNA Repair ; Eukaryotic Cells/physiology ; Meiosis ; *Models, Biological ; Recombination, Genetic ; *Reproduction ; }, abstract = {The theory is presented that the sexual process is a repair mechanism which maintains redundancy within the sub-structure of hierarchical, self-reproducing organisms. In order to keep the problems within mathematically tractable limits (see Part II), a simple model is introduced: a wheel with 6 spokes, 3 of them vital and 3 redundant, symbolizes the individual (cell or organism). Random accidents destroy spokes; the wheels replicate at regular cycles and engage periodically in pairing and repair phases during which missing spokes are copy-reproduced along the intact spokes of the partner wheel. The hierarchical structure of such a system is analysed and an 'autonomous unit' is defined: this is the unit of minimal hierarchical complexity which is capable of perpetuating autonomously all higher and all lower levels of the hierarchy; this is the central unit of selection. Four basic, physical parameters are isolated which determine the essential features of any eucaryotic life cycle: 1. The number of levels of the hierarchy (unicellular, multicellular, colonial, etc.); 2. the relation between the phases of replication (asexual generations) and repair (sexual generations); 3. the duration of potential repair (haplo-diplo-phase); 4. the position of the sexual partners within the hierarchy (selfing, monecy, dioecy, reproductive individuals within colonies, etc.). The evaluation of fitness components is considered in relation to trends of reproductive patterns in evolution.}, } @article {pmid74018, year = {1977}, author = {Hildemann, WH and Raison, RL and Cheung, G and Hull, CJ and Akaka, L and Okamoto, J}, title = {Immunological specificity and memory in a scleractinian coral.}, journal = {Nature}, volume = {270}, number = {5634}, pages = {219-223}, doi = {10.1038/270219a0}, pmid = {74018}, issn = {0028-0836}, mesh = {Animals ; Biological Evolution ; Cnidaria/*immunology ; Epitopes ; Graft Rejection ; Histocompatibility Antigens/*analysis/genetics ; *Immunologic Memory ; Polymorphism, Genetic ; }, abstract = {Tissue transplantation immunity with a specific memory component is demonstrated in populations of Montipora. This highly discriminating immunoreactivity derives from extensive allogeneic polymorphism of histocompatibility (H) markers. An H system of immunorecognition is postulated to have originated in multicellular invertebrates probably beginning with coelenterates.}, } @article {pmid895789, year = {1977}, author = {Fialkow, PJ and Jackson, CE and Block, MA and Greenawald, KA}, title = {Multicellular origin of parathyroid "adenomas".}, journal = {The New England journal of medicine}, volume = {297}, number = {13}, pages = {696-698}, doi = {10.1056/NEJM197709292971304}, pmid = {895789}, issn = {0028-4793}, mesh = {Adenoma/enzymology/*pathology ; Female ; Glucosephosphate Dehydrogenase/analysis ; Humans ; Hyperparathyroidism/pathology ; Hyperplasia ; Isoenzymes/analysis ; Middle Aged ; Parathyroid Glands/enzymology/pathology ; Parathyroid Neoplasms/enzymology/*pathology ; }, abstract = {Most cases of primary hyperparathyroidism are associated with enlargement of a single gland (i.e., an "adenoma") or with chief-cell hyperplasia, but there is controversy about the relative frequency of each of these entities. It has even been postulated that adenomas do not arise spontaneously, bu- result from prolonged hyperplasia in response to unknown stimuli. We studied four parathyroid adenomas from three women with heterozygosity (GdB/GdA) for the X-chromosome-linked enzyme, glucose-6-phosphate dehydrogenase, to determine the number of cells from which the growths arise. Unicellular origin would be compatible with a rare oncogenic event, whereas multicellular origin might be seen with hyperplasia. Both B and A isoenzymes were found in each "adenoma" in proportions similar to those observed in normal tissues, indicating that the lesions have multicellular origin. Thus, parathyroid hyperplasia and adenomas, which at best are difficult to distinguish from one another pathologically, may also be similar biologically.}, } @article {pmid301813, year = {1977}, author = {Mezger-Freed, L}, title = {Chromosomal evolution in a haploid frog cell line: implications for the origin of karyotypic variants.}, journal = {Chromosoma}, volume = {62}, number = {1}, pages = {1-15}, pmid = {301813}, issn = {0009-5915}, mesh = {Animals ; Anura ; *Cell Line ; *Chromosomes ; Haploidy ; *Rana pipiens ; Time Factors ; Translocation, Genetic ; }, abstract = {ICR 2A, a haploid cell line derived from Rana pipiens embryos, has remained haploid in number of chromosones and their relative lengths and centromere positions for 500 cell generations. After this time, two new haryotypes appeared; relative length measurements indicate that the first has a translocation from chromosome 4 to 6, the second translocations from 3 and 4 to 6 and 7. The single exchange karyotype is not a precursor for the double exchange according to a statistical analysis. The double exchange karyotype characterized 90% of some cultures although a selective advantage could not be demonstrated for these cells. The observations suggest that a non-clonal or multicellular origin may account for these karyotypic variants.}, } @article {pmid560178, year = {1977}, author = {Jenkins, CL and Kuhn, DA and Daly, KR}, title = {Fatty acid composition of Simonsiella strains.}, journal = {Archives of microbiology}, volume = {113}, number = {3}, pages = {209-213}, pmid = {560178}, issn = {0302-8933}, mesh = {Animals ; Cats ; Dogs ; Fatty Acids/*analysis ; Gram-Negative Aerobic Bacteria/analysis/*classification ; Humans ; Mouth/microbiology ; Sheep ; }, abstract = {Gas-liquid chromatography of methyl esters of bound fatty acids extracted from the cells of 48 Simonsiella strains showed that these aerobic, gliding, multicellular-filamentous bacteria have fatty acid profiles of the pattern considered typical of Gram-negative eubacteria. All strains contained predominantly tetradecanoic acid (29.5%), 9-hexadecenoic acid (22.2%), an unidentified acid with an equivalent chain length of approximately 20 carbon atoms (15.8%), and dodecanoic acid (11.4%). Discriminant analysis of the mean relative percentages of 12 fatty acids correctly assigned 94% of the strains to groups based on their source of origin (i.e., the oral cavities of sheep, cat, human or dog); the relative amounts of only 3 of the fatty acids (9-octadecenoic acid, hexadecanoic acid, and tetradecanoic acid) provided most of this discrimination.}, } @article {pmid140943, year = {1977}, author = {Sutherland, RM and MacDonald, HR and Howell, RL}, title = {Multicellular spheroids: a new model target for in vitro studies of immunity to solid tumor allografts.}, journal = {Journal of the National Cancer Institute}, volume = {58}, number = {6}, pages = {1849-1853}, doi = {10.1093/jnci/58.6.1849}, pmid = {140943}, issn = {0027-8874}, mesh = {Animals ; Antigens, Neoplasm/administration & dosage ; Clone Cells/immunology ; *Cytological Techniques ; Cytotoxicity Tests, Immunologic ; Female ; *Immunity, Cellular ; In Vitro Techniques ; Lymphocyte Culture Test, Mixed ; Lymphocytes/immunology ; Mammary Neoplasms, Experimental/*immunology ; Mice ; Mice, Inbred Strains ; Neoplasm Transplantation ; Sarcoma, Experimental/*immunology ; Spleen/immunology ; Transplantation, Homologous ; }, abstract = {Multicellular spheroids of EMT6 mammary sarcoma cells of BALB/c origin were incubated with normal spleen cells or alloimmune spleen cells generated in vitro in mixed leukocyte cultures (MLC). After 24 hours, spheroids were trypsinized and assayed for surviving tumor cells by use of a cloning technique. Under these conditions a 60-80% reduction in clone-forming tumor cells was observed after incubation of spheroids with immune lymphocytes as compared to normal lymphocyte controls. This cytotoxic effect occurred in situ, and alloimmune cells sensitized against unrelated antigens were much less cytotoxic than were specifically sensitized cells. In parallel autoradiographic studies, some immune lymphoid cells that had been labeled with tritiated thymidine during the proliferative phase of the MLC could be demonstrated within spheroids after 24 hours. These results suggested that multicellular spheroids will be a useful in vitro model for more detailed analysis of the factors controlling infiltration in in situ destruction of solid tumor grafts.}, } @article {pmid558051, year = {1977}, author = {Takeuchi, J and Sobue, M and Shamoto, M and Yoshida, M and Sato, E and Leighton, J}, title = {Cell surface glycosaminoglycans of cell line MDCK derived from canine kidney.}, journal = {Cancer research}, volume = {37}, number = {5}, pages = {1507-1512}, pmid = {558051}, issn = {0008-5472}, mesh = {Animals ; Cell Line ; Cell Membrane/*metabolism ; Dogs ; Epithelial Cells ; Glycosaminoglycans/*metabolism ; Heparitin Sulfate/metabolism ; Hyaluronic Acid/metabolism ; Kidney ; Sulfates/metabolism ; }, abstract = {Morphological observations and biochemical analysis were made on glycosaminoglycans produced by MDCK cells of dog kidney origin growing on a glass surface as a mosaic of epithelium with many multicellular hemishperical vesicles. MDCK cells synthesized glycosaminoglycans, which consisted mainly of heparan sulfate and hyaluronic acid. The majority of the substances were contained in a cell-surface component removable with ethylenediaminetetraacetic acid-trypsin. In the radioautograph of tissue sections, high radioactivity of 35SO4 was observed on the medium-bathed cell surface, where Alcian blue-strained material could be observed. Ultrastructurally, the surface of microvillous processes which were abundant on the cell surface in contact with the medium was stained with ruthenium red. A small amount of chondroitin 4- and 6-sulfates were also synthesized. After 24 hr, the majority of chondrotin [35S] sulfates newly formed were secreted into the cultured medium, whereas haparan [35S] sulfate was released much less, remaining as a cellular component. The biological roles of glyconsaminoglycans produced by epithelial cells are discussed.}, } @article {pmid318268, year = {1977}, author = {Hellung-Larsen, P and Frederiksen, S}, title = {Occurrence and properties of low molecular weight RNA components from cells at different taxonomic levels.}, journal = {Comparative biochemistry and physiology. B, Comparative biochemistry}, volume = {58}, number = {3}, pages = {273-281}, doi = {10.1016/0305-0491(77)90202-4}, pmid = {318268}, issn = {0305-0491}, mesh = {Animals ; Cells, Cultured ; Chromatography, Gel ; Cricetinae ; Electrophoresis, Polyacrylamide Gel ; Humans ; Mice ; Molecular Weight ; RNA, Small Nuclear/*analysis ; Rats ; Species Specificity ; }, abstract = {1. The occurrence and gel electrophoretic properties of low molecular weight RNA components (LMW RNA) have been studied in species at different taxonomic levels. The LMW RNA components apart from tRNA, 5S RNA and 5.5S RNA are called LMW*RNA. 2. The major components of LMW*RNA in mammalian cells are L, A, C and D, accounting for 0.1-0.7% of cellular RNA. The gel electrophoretic migration of components L, C, and D is similar in different mammals but the migration of component A shows differences. 3. Amphibia, reptiles and birds contain L, A, C and D in about the same amounts as mammals but slight differences in migration are seen for L, C and D. Component A is absent from the nucleated red blood cells of the chicken and the frog. 4. Sea urchins contain three LMW*RNA components with migrations different from L, A, C and D. These components account for about 0.1% of the cellular RNA. 5. Insects contain only one LMW*RNA component, migrating as component L. 6. Tetrahymena, Physarum and Mycoplasmas have one component which may be a counterpart to component L in higher cells. Yeast shows no LMW*RNA components. 7. In the multicellular species the occurrence and gel electrophoretic migration of LMW*RNA components are not related to tumorigenicity, developmental stage or origin of tissue.}, } @article {pmid982576, year = {1976}, author = {Glasnikova, A and Miklovichova, M}, title = {[Pollen development in the anthers of several cereal strains and hybrids during cultivation in vitro].}, journal = {TSitologiia i genetika}, volume = {10}, number = {5}, pages = {444-449}, pmid = {982576}, issn = {0564-3783}, mesh = {Edible Grain/*growth & development ; Hybridization, Genetic ; In Vitro Techniques ; *Pollen ; Secale/*growth & development ; Species Specificity ; Triticum/*growth & development ; }, abstract = {In order to induce androgenesis in vitro anthers of some cereals were cultivated. The highest number of proembryos was obtained in the hybrid Triticale in F3 generation on Blayder's medium supplemented with 3 and 12% sucrose. Proembryos represented multi-nuclear and multicellular formations which stagnated at the globular stage of development. Origin of roots from calluses was not accompanied by formation of buds. There was no formation of embryos from pollen grains in case of lines Triticum aestivum and Secale cereale.}, } @article {pmid949727, year = {1976}, author = {Bittner, GD and Mann, DW}, title = {Differential survival of isolated portions of crayfish axons.}, journal = {Cell and tissue research}, volume = {169}, number = {3}, pages = {301-311}, pmid = {949727}, issn = {0302-766X}, mesh = {Animals ; Astacoidea/*physiology ; *Axons/ultrastructure ; Biological Transport ; Motor Neurons ; *Nerve Degeneration ; Neuroglia/*physiology/ultrastructure ; Neurons, Afferent ; Phagocytosis ; Time Factors ; Tissue Survival ; }, abstract = {Electron microscopic studies show that transplanted segments of sensory axons of varying lengths degenerate within 7-14 days whereas transplanted segments of crustacean motor axons survive morphologically intact for 20-30 days. The middle portion of an isolated motor axon segment degenerates less rapidly than portions of the same axon located nearer the periphery or nearer the ventral nerve cord. One week after transplantation, glial cells appear to phagocytize sensory axons whereas glial cells around motor axons appear to hypertrophy and to have more rough endoplasmic reticulum. After three weeks, motor axons also appear to be phagocytized by glial cells. These data suggest that the glia surrounding isolated motor axons can change from a supportive to a destructive function, whereas glial cells surrounding severed sensory axons primarily have a destructive function. These and other data also indicate that crustacean motor axons receive significant trophic inputs from their own perikaryon, from post-synaptic contacts, and from adjacent glial cells. The possibility that adjacent healthy cells may supply metabolically deficient cells with needed substances could be a significant adaptive advantage for the evolution of multicellular organisms.}, } @article {pmid971121, year = {1976}, author = {Pozhidaev, EA}, title = {[Patterns characterizing different levels of animal organization].}, journal = {Arkhiv anatomii, gistologii i embriologii}, volume = {70}, number = {5}, pages = {74-78}, pmid = {971121}, issn = {0004-1947}, mesh = {Animal Population Groups/*anatomy & histology/growth & development ; Animals ; Biological Evolution ; Cell Nucleus ; Cytoplasm ; Species Specificity ; }, abstract = {The article deals with features of the regularities characterizing different levels of organization of the animal body. The cell is not only an integrated but also indivisible organic integrity which is due to the interaction of the nucleus and cytoplasm determining all sides of its vital activity. From this viewpoint the results of experiments on transplantation of the embryo cell nucleus into an enucleated egg of amphibia and the data on somatic hybridization are estimated. All processes of the cell life, their growth, multiplication and differentiation develop within the tissue system and are determined by the regularities of its development. The integrated system of the organism of a multicellular animal unites all the forms of integration of multi-step systemic pattern at different organization levels. Among different categories the systems of tissues and their interaction within the organ are most integrated. The regularities of the tissue development can not be brough to the regularities of the development of the anatomical structure of organs. The integration of cell elements in a tissue system and intertissue relations is the basis of all forms of interdependence in the cell development and the organism structure.}, } @article {pmid5987, year = {1976}, author = {Ivanov, AV}, title = {[New support for the theory of I.I. Mechnikov concerning the origin of multicellular animals].}, journal = {Arkhiv anatomii, gistologii i embriologii}, volume = {70}, number = {3}, pages = {53-57}, pmid = {5987}, issn = {0004-1947}, mesh = {Animals ; *Biological Evolution ; Cnidaria/*anatomy & histology ; History, 19th Century ; }, } @article {pmid1248901, year = {1976}, author = {Friedman, JM and Fialkow, PJ}, title = {Viral "tumorigenesis" in man: cell markers in condylomata acuminata.}, journal = {International journal of cancer}, volume = {17}, number = {1}, pages = {57-61}, doi = {10.1002/ijc.2910170109}, pmid = {1248901}, issn = {0020-7136}, mesh = {Adolescent ; Adult ; Condylomata Acuminata/*genetics ; Female ; Genes ; *Glucosephosphate Dehydrogenase ; Heterozygote ; Humans ; Phenotype ; }, abstract = {Determination of the glucose-6-phosphate dehydrogenase (G-6-PD) phenotype of a neoplasm occurring in a heterozygous female can be used to trace the cellular origin of the tumor. This technique was performed on 834 individual verrucous subunits from four condylomata acuminata (venereal warts) arising in two patients heterozygous for a B and an A gene at the G-6-PD locus. All four specimens contained both A and B types of G-6-PD. Furthermore, even single verrucous subunits from each specimen occasionally contained both enzyme types. These data indicate that condylomata acuminata have a multicellular origin. The initial number of cells which, after viral infection, developed into a condyloma acuminatum was estimated to be about 4,400 cells, on the basis of statistical analysis of the data in one case.}, } @article {pmid1211434, year = {1975}, author = {Quevedo, WC and Fitzpatrick, TB and Pathak, MA and Jimbow, K}, title = {Role of light in human skin color viariation.}, journal = {American journal of physical anthropology}, volume = {43}, number = {3}, pages = {393-408}, doi = {10.1002/ajpa.1330430321}, pmid = {1211434}, issn = {0002-9483}, mesh = {Animals ; Asian People ; Biological Evolution ; Black People ; Climate ; Genes ; Hormones/physiology ; Humans ; *Light ; Melanins/metabolism ; Melanocyte-Stimulating Hormones/physiology ; Melanocytes/physiology/ultrastructure ; Native Hawaiian or Other Pacific Islander ; Organoids/physiology ; Reproduction ; Seasons ; Skin/cytology/growth & development ; *Skin Pigmentation/radiation effects ; Ultraviolet Rays ; White People ; }, abstract = {The major source of color in human skin derives from the presence within the epidermis of specialized melanin-bearing organelles, the melanosomes. Tanning of human skin on exposure to ultraviolet light results from increased amounts of melanin within the epidermis. Melanosomes synthesized by melanocytes are acquired by keratinocytes and transported within them to the epidermal surface. In some cases, the melanosomes are catobolized en route. New information indicates that the multicellular epidermal melanin unit (melanocyte and associated pool of keratinocytes) rather than the melanocyte alone is the focal point for the control of melanin metabolism within mammalian epidermis. Gross human skin color derives from the visual impact of the summed melanin pigmentation of the many epidermal melanin units. In theory, constitutive skin color in man designates the genetically-determined levels of melanin pigmentation developed in the absence of exposure to solar radiation or other environmental influences; facultative skin color or "tan" characterizes the increases in melanin pigmentation above the constitutive level induced by ultraviolet light. The details of genetic regulation of pigment metabolism within the epidermal melanin units are being clarified. In some mammals at least, the function of epidermal melanin units is significantly influenced by hormones which may be regulated by radiations received through the eyes. Based on an evolutionary history of the human family which exceeds ten million years, it is proposed that melanin pigmentation may have played a number of roles in human adaptions to changing biologic and physical environments.}, } @article {pmid173929, year = {1975}, author = {Warner, TF and Krueger, RG}, title = {The multicellular (as opposed to the monoclonal) origin of the murine myeloma cell.}, journal = {Journal of theoretical biology}, volume = {54}, number = {2}, pages = {175-179}, doi = {10.1016/s0022-5193(75)80122-6}, pmid = {173929}, issn = {0022-5193}, mesh = {Animals ; Cell Fusion ; Cell Transformation, Neoplastic ; *Hybrid Cells ; Macrophages ; Mice ; Mice, Inbred BALB C ; *Multiple Myeloma/immunology ; Neoplasms, Experimental ; Plasma Cells ; Retroviridae ; }, } @article {pmid1127024, year = {1975}, author = {Loiseaux, S and Mache, R and Rozier, C}, title = {Rifampicin inhibition of the plastid rRNA synthesis of Marchantia polymorpha.}, journal = {Journal of cell science}, volume = {17}, number = {3}, pages = {327-335}, doi = {10.1242/jcs.17.3.327}, pmid = {1127024}, issn = {0021-9533}, mesh = {Bacteria/metabolism ; Chloroplasts/drug effects/metabolism ; Electrophoresis, Polyacrylamide Gel ; Plants/drug effects/*metabolism/microbiology ; RNA, Ribosomal/*biosynthesis ; Ribosomes/drug effects/metabolism ; Rifampin/*pharmacology ; Transcription, Genetic/drug effects ; }, abstract = {The effect of rifampicin on the synthesis of plastid rRNA in Marchantia polymorpha was studied in vivo. As bacterial rRNA and plastid rRNA have the same electrophoretic mobilities, this study was possible only after a method for inhibiting bacterial contamination was developed. It was established that 91-100% of the rRNA synthesized by cultures of bacteria from Marchantia, after a labelling period of 3 and 9 h by 32-P, is inhibited by 10 mug/ml of rifampicin. The same inhibition was observed when Marchantia was labelled for 3 h in the presence of 10 mug/ml of rifampicin, showing that no plastid rRNA was synthesized under out conditions, but only bacterial RNA. However, when labelling was continued for 9 h two important peaks of rRNA (23 and 19 s) were labelled in the presence of 10 or 20 mug/ml of rifampicin. These peaks are of chlorophastic origin as confirmed by the following facts: the labelling is light-activated; plastids isolated from thalli labelled for 12 h also show these two radioactive peaks. Cytoplasmic rRNA is synthesized under certain conditions. The synthesis of plastid rRNA is inhibited by higher concentrations of rifampicin, a concentration of 250 mug/ml producing at least 75% inhibition. Marchantia, a primitive multicellular plant, differs in this respect from higher plants, which seem to be, in most cases, insensitive to rifampicin}, } @article {pmid4152810, year = {1974}, author = {McMahon, D}, title = {Chemical messengers in development: a hypothesis.}, journal = {Science (New York, N.Y.)}, volume = {185}, number = {4156}, pages = {1012-1021}, doi = {10.1126/science.185.4156.1012}, pmid = {4152810}, issn = {0036-8075}, mesh = {Adenylyl Cyclases/metabolism ; Adrenergic alpha-Agonists/pharmacology ; Adrenergic beta-Agonists/pharmacology ; Adrenergic beta-Antagonists/pharmacology ; Animals ; Anura ; *Cell Differentiation ; Cell Division ; Chick Embryo ; Collagen/physiology ; Cyclic AMP/physiology ; Cyclic GMP/physiology ; *Embryonic and Fetal Development ; Enzyme Activation/drug effects ; Humans ; *Ions ; Macromolecular Substances ; Mice ; Models, Biological ; Neurotransmitter Agents/pharmacology/physiology ; Nucleotides, Cyclic/metabolism/*physiology ; Rats ; Transcription, Genetic ; Transduction, Genetic ; }, abstract = {The hypothesis that physiological and developmental regulatory mechanisms are similar has been presented. Well-known developmental systems chosen illustrate the capability of the model to suggest a simple mechanism underlying the effects on development of a diverse group of chemicals. This hypothesis might be applied to other systems including the induction of the lens, limb regeneration, and the induction of the head of hydra (124). I have proposed this hypothesis not only because it permits consideration of a complex and varied array of experimental observations as reflections of a simple basic biochemical mechanism, but because recent technical advances in instrumentation and methods allow it to be directly tested. The fluorescent antibody method for the cytochemical measurement of cyclic nucleotides provides a means for investigating changes in the concentrations of cyclic nucleotides in developing cells and could also be used to detect neurotransmitters in developing cells. Similarly, the scanning electron microscope in the emitted x-ray mode provides a method for measuring changes in the content and distribution of cations within developing cells. The hypothesis presented here suggests pleasing asceticism on the part of eukaryotes. It suggests that simple derivatives of metabolites, including neurotransmitters and cyclic nucleotides, are linked together as regulatory molecules throughout the eukaryotes. The neurotransmitters are suggested to have a more general role in information transmission in eukaryotes than is generally accepted. They are hypothesized to have progressed during evolution from being intracellular messengers to a role as intercellular messengers for the relatively slow communication of developmental informatbn; and, finally, this process has culminated with their participation in the rapid intercellular communication mediated by nerves. The thought that the complex pictures of physiological regulation and of the construction of a complex multicellular organism like man might be painted with so few colors is quite satisfying.}, } @article {pmid4754778, year = {1973}, author = {Savost'ianov, GA}, title = {[Representation of the evolution of a multicellular organism in the form of a periodic table of cellular phenotypes].}, journal = {Doklady Akademii nauk SSSR}, volume = {213}, number = {1}, pages = {213-216}, pmid = {4754778}, issn = {0002-3264}, mesh = {*Biological Evolution ; Ecology ; Models, Biological ; *Periodicity ; *Phenotype ; }, } @article {pmid4577623, year = {1973}, author = {Fialkow, PJ and Klein, E and Klein, G and Clifford, P and Singh, S}, title = {Immunoglobulin and glucose-6-phosphate dehydrogenase as markers of cellular origin in Burkitt lymphoma.}, journal = {The Journal of experimental medicine}, volume = {138}, number = {1}, pages = {89-102}, pmid = {4577623}, issn = {0022-1007}, mesh = {Animals ; B-Lymphocytes/immunology ; *Burkitt Lymphoma/enzymology/immunology ; Cell Membrane/immunology ; Clone Cells ; Female ; Fluorescent Antibody Technique ; Glucosephosphate Dehydrogenase/*analysis ; Heterozygote ; Humans ; Immunoglobulin Fragments/analysis ; Immunoglobulin G/analysis ; Immunoglobulin M/analysis ; Immunoglobulins/*analysis ; Isoenzymes/analysis ; Jaw Neoplasms/enzymology/immunology ; Male ; Neoplasms, Multiple Primary/enzymology/immunology ; Ovarian Neoplasms/enzymology/immunology ; Rabbits/immunology ; }, abstract = {Two independent marker systems, G-6-PD isoenzymes and cell membrane-associated IgM, were used to trace the cellular origin of Burkitt lymphoma. Application of the G-6-PD system is dependent upon the fact that, in accordance with inactivity of one X chromosome in each somatic cell, females heterozygous for the usual B gene (Gd(B)) at the X-linked G-6-PD locus and the variant allele Gd(A) (or Gd(A-)) have two types of cells. Gd(B) is active in one cell population, which consequently produces B type enzyme; in the other population Gd(A) is active, producing the variant A enzyme. Therefore, tumors with a clonal origin in a Gd(B)/Gd(A) heterozygote should exhibit only one enzyme type (B or A) whereas those with multicellular origin may show both A and B enzymes. Utilization of the immunoglobulin system is based upon the supposition that in lymphoid neoplasms with clonal origin either all or none of the tumor cells should have surface-associated IgM and kappa-reactivities. 33 of 34 relatively homogeneous (with respect to content of neoplastic cells) individual Burkitt tumors from 19 G-6-PD heterozygotes had single enzyme phenotypes. Similarly, of 95 tumors tested, 92 consisted essentially of IgM(+) or (-) cells. Two neoplasms could not be definitely classified and one tumor had two cell populations. These data suggest a clonal origin for most Burkitt tumors, but the one neoplasm with a double G-6-PD phenotype (A/B) and the one tumor that had two populations of cells with respect to surface IgM, could have originated from multiple cells. G-6-PD was determined in each of two tumors from seven heterozygotes and in all cases both tumors had the same single enzyme phenotype. Surface-associated IgM was tested in four tumors from one patient, three from another, and in two neoplasms from 11 patients. With one exception, all tumors from the same patient were concordant with respect to IgM. These findings suggest that the entire disease has a clonal origin, i.e., it emerges at one focus and then spreads to other parts of the body. Cells from 36 recurrent neoplasms were typed for G-6-PD (in heterozygotes) and/or IgM. In one previously reported patient, initial and recurrent tumors were discordant for G-6-PD. Two other patients had IgM phenotypes in recurrences that were discordant with those found in their initial tumors. Phenotypes from three of nine relapses which occurred after 5 mo were discordant for G-6-PD or IgM but no discordance was detected among 27 earlier recurrences. Thus, some "late" recurrences may be due to emergence of "new" maligant cell lines whereas most early relapses are due to reemergence of the original malignant clones. The probable unicellular origin of Burkitt lymphoma and the findings in tumor recurrences are discussed in terms of the disease's putative viral etiology.}, } @article {pmid4504336, year = {1972}, author = {Darlington, PJ}, title = {Nonmathematical concepts of selection, evolutionary energy, and levels of evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {69}, number = {5}, pages = {1239-1243}, pmid = {4504336}, issn = {0027-8424}, mesh = {*Biological Evolution ; Brain/growth & development ; Humans ; *Selection, Genetic ; Thinking ; }, abstract = {The place of mathematics in hypotheticodeductive processes and in biological research is discussed. (Natural) Selection is defined and described as differential elimination of performed sets at any level. Sets and acting sets are groups of units (themselves sets of smaller units) at any level that may or do interact. A pseudomathematical equation describes directional change (evolution) in sets at any level. Selection is the ram of evolution; it cannot generate, but can only direct, evolutionary energy. The energy of evolution is derived from molecular or chemical levels, is transmitted upwards through the increasingly complex sets of sets that form living systems, and is turned in directions determined by the sum of selective processes, at different levels, which may either supplement or oppose each other. All evolutionary processes conform to the pseudomathematical equation referred to above, use energy as described above, and have a P/OE (ratio of programming to open-endedness) that cannot be measured, but can be related to other P/OE values. Phylogeny and ontogeny are compared as processes af directional change with set selection. Stages in the evolution of multi-cellular individuals are suggested, and are essentially the same as stages in the evolution of some multi-individual insect societies. Thinking is considered as a part of ontogeny involving an irreversible, nonrepetitive process of set selection in the brain.}, } @article {pmid4943851, year = {1971}, author = {Yunis, JJ and Yasmineh, WG}, title = {Heterochromatin, satellite DNA, and cell function. Structural DNA of eucaryotes may support and protect genes and aid in speciation.}, journal = {Science (New York, N.Y.)}, volume = {174}, number = {4015}, pages = {1200-1209}, doi = {10.1126/science.174.4015.1200}, pmid = {4943851}, issn = {0036-8075}, mesh = {Animals ; Biological Evolution ; Cattle ; Cell Nucleus/analysis ; *Chromosomes/analysis ; Congenital Abnormalities/genetics ; *Cytogenetics ; DNA/analysis/*physiology ; Guinea Pigs ; Heterochromatin/analysis/*physiology ; Humans ; Karyotyping ; Meiosis ; Mice ; Mitosis ; Mutation ; Neoplasms/genetics ; Nucleic Acid Hybridization ; Nucleotides/analysis ; Phenotype ; Recombination, Genetic ; Sex Chromosomes ; Species Specificity ; }, abstract = {With the assumption that a portion that comprises some 10 percent of the genomes in higher organisms cannot be without a raison d'être, an extensive review led us to conclude that a certain amount of constitutive heterochromatin is essential in multicellular organisms at two levels of organization, chromosomal and nuclear. At the chromosomal level, constitutive heterochromatin is present around vital areas within the chromosomes. Around the centromeres, for example, heterochromatin is believed to confer protection and strength to the centromeric chromatin. Around secondary constrictions, heterochromatic blocks may ensure against evolutionary change of ribosomal cistrons by decreasing the frequency of crossing-over in these cistrons in meiosis and absorbing the effects of mutagenic agents. During meiosis heterochromatin may aid in the initial alignment of chromosomes prior to synapsis and may facilitate speciation by allowing chromosomal rearrangement and providing, through the species specificity of its DNA, barriers against cross-fertilization. At the nuclear level of organization, constitutive heterochromatin may help maintain the proper spatial relationships necessary for the efficient operation of the cell through the stages of mitosis and meiosis. In the unicellular procaryotes, the presence of a small amount of genetic information in one chromosome obviates the need for constitutive heterochromatin and a nuclear membrane. At higher levels of organization, with an increase in the size of the genome and with evolution of cellular and sexual differentiation, the need for compartmentalization and structural components in the nucleus became imminent. The portion of the genome that was concerned with synthesis of ribosomal RNA was enlarged and localized in specific chromosomes, and the centromere became part of each chromosome when the mitotic spindle was developed in evolution. Concomitant with these changes in the genome, repetitive sequences in the form of constitutive heterochromatin appeared, probably as a result of large-scale duplication. The repetitive DNA's were kept through natural selection because of their importance in preserving these vital regions and in maintaining the structural and functional integrity of the nucleus. The association of satellite (or highly repetitive) DNA with constitutive heterochromatin is understandable, since it stresses the importance of the structural rather than transcriptional roles of these entities. Nuclear satellite DNA's have one property in common despite their species specificity, namely heterochromatization. In this sense the apparent species specificity of satellite DNA may be the result of natural selection for duplicated short polynucleotide segments that are nontranscriptional and can be utilized in specific structural roles.}, } @article {pmid5762397, year = {1969}, author = {Leighton, J and Brada, Z and Estes, LW and Justh, G}, title = {Secretory activity and oncogenicity of a cell line (MDCK) derived from canine kidney.}, journal = {Science (New York, N.Y.)}, volume = {163}, number = {3866}, pages = {472-473}, doi = {10.1126/science.163.3866.472}, pmid = {5762397}, issn = {0036-8075}, mesh = {Adenocarcinoma/etiology ; Animals ; Brain Neoplasms/etiology ; Cell Transformation, Neoplastic ; Chick Embryo ; *Culture Techniques ; Dogs ; Kidney/cytology ; Neoplasm Metastasis ; Neoplasms, Experimental/*etiology ; }, abstract = {A cell line (MDCK) of dog kidney origin grows on a glass surface as a mosaic of epithelium with many multicellular hemispherical vesicles. The cells lining the blisters actively secrete into the cyst cavities. Suspensions of these cells injected intravenously in the chick embryo produce brain metastases resembling adenocarcinoma.}, } @article {pmid4903215, year = {1968}, author = {Berdyshev, GD}, title = {[Genetic degeneration of cells. Its mechanisms and significance in the multicellular organism].}, journal = {Uspekhi sovremennoi biologii}, volume = {66}, number = {2}, pages = {226-246}, pmid = {4903215}, issn = {0042-1324}, mesh = {*Aging ; Amphibians ; Animals ; Biological Evolution ; *Cytogenetics ; Death ; Insecta ; Mutation ; Regeneration ; }, } @article {pmid5754697, year = {1968}, author = {Ivanov, AV}, title = {[Recent status of the question of the origin of multicellular animals].}, journal = {Zhurnal obshchei biologii}, volume = {29}, number = {1}, pages = {25-30}, pmid = {5754697}, issn = {0044-4596}, mesh = {*Animal Population Groups ; Animals ; *Biological Evolution ; }, } @article {pmid6016897, year = {1967}, author = {Henderson, JS}, title = {Adjuvators to the propagation of mouse mammary tumor cells on expanses of subcutaneous tissue.}, journal = {The Journal of experimental medicine}, volume = {125}, number = {1}, pages = {71-89}, pmid = {6016897}, issn = {0022-1007}, mesh = {Animals ; *Connective Tissue ; *Culture Techniques ; Liver ; *Mammary Neoplasms, Experimental ; Mice ; Trypsin ; }, abstract = {The cells of a mouse mammary cancer were obtained with enzymes in suspensions which could be filtered to exclude all which were not single and most which were already dead. Heavy suspensions of these individual cells were plated over the dorsal subcutaneous expanses of female weanling mice where they implanted and grew to form coalescent tumors covering the back more or less entirely. Sparser suspensions, similarly plated (a) gave rise to fewer tumors, and (b) gave rise to tumors reaching measurable size later. These two consequences of sparser plating left room for the testing of adjuvators to transplantation. Adjuvator effects were obtained by splitting the subcutaneous expanses beforehand and by injecting liver along with the plated cells. Through 28 plated generations over 4 yr the tumor maintained completely stable, morphological heterogeneity. These findings with a complex tumor indicate strongly that its heterogeneity comes not from repeated cellular mutation late in its development, but from diverse potentiality to give rise to cells of specific and differing character, inherent in its individual cells at the time of its multicellular origin.}, } @article {pmid5859924, year = {1965}, author = {Goldfine, H}, title = {The evolution of oxygen as a biosynthetic reagent.}, journal = {The Journal of general physiology}, volume = {49}, number = {1}, pages = {Suppl:253-74}, pmid = {5859924}, issn = {0022-1295}, mesh = {Carotenoids/biosynthesis ; Coenzymes/biosynthesis ; Enterobacter/metabolism ; Fatty Acids/*biosynthesis ; In Vitro Techniques ; Nicotinic Acids/biosynthesis ; Oxygen/*metabolism ; Porphyrins/biosynthesis ; Quinones/biosynthesis ; Staphylococcus/metabolism ; Sterols/biosynthesis ; Tyrosine/biosynthesis ; }, abstract = {THE BIOSYNTHESIS OF CERTAIN CELL CONSTITUENTS: monounsaturated fatty acids, tyrosine, and nicotinic acid, is oxygen-dependent in many higher organisms. The same compounds can be synthesized by different, oxygen-independent pathways in lower organisms. The general outlines of these pathways are described and the importance of the compounds synthesized is discussed. An examination of the distribution of these pathways among living organisms reveals that oxygen-dependent pathways replaced the "anaerobic" pathways at different branch points on the evolutionary tree. Other groups of compounds are discussed, which are not distributed as widely among living organisms, but are found in all higher organisms. These compounds have specialized functions and their biosynthesis requires molecular oxygen. The oxygen-dependent portions of the biosynthetic pathways leading to porphyrins, quinone coenzymes, carotenoids, sterols, and polyunsaturated fatty acids are summarized. The distribution and functions of these compounds are also considered and an attempt is made to place them in the framework of evolution. While sterols and polyunsaturated fatty acids are found exclusively in the higher Protista and multicellular organisms, carotenoids, porphyrins, and quinones are also found in bacteria. The possibility of oxygen-independent mechanisms for their biosynthesis is discussed.}, } @article {pmid14421673, year = {1960}, author = {MARTIN, GJ}, title = {Stentor monsters: an approach to the origin of multicellular organisms.}, journal = {Archiv fur Kreislaufforschung}, volume = {33}, number = {}, pages = {158-176}, pmid = {14421673}, issn = {0003-9217}, mesh = {Abnormalities, Severe Teratoid/*genetics ; *Ciliophora ; Humans ; }, }